Unveiling the Effects of Linker Substitution in Suzuki Coupling with Palladium Nanoparticles in Metal–Organic Frameworks [Unveiling the Effects of Linker Substitution in Suzuki Coupling Reaction with Palladium Nanoparticles in Metal–Organic Frameworks

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Xinle; Zhang, Biying; Van Zeeland, Ryan

The establishment of structure–property relationships in heterogeneous catalysis is of prime importance but remains a formidable challenge. Metal–organic frameworks (MOFs) featuring excellent chemical tunability are emerging as an auspicious platform for the atomic-level control of heterogeneous catalysis. Herein, we encapsulate palladium nanoparticles (Pd NPs) in a series of isoreticular mixed-linker MOFs, and the obtained MOF-Pd NPs catalysts were used to unveil the electronic and steric effects of linker substitution on the activity of these catalysts in the Suzuki–Miyaura cross-coupling reactions. Significantly, m-6,6'-Me2bpy-MOF-Pd exhibits a remarkable enhancement in the activity compared to non-functionalized m-bpy-MOF-Pd and m-4,4'-Me 2bpy-MOF-Pd. This study unambiguously demonstratesmore » that the stereoelectronic properties of linker units are crucial to the catalytic activity of nanoparticles encapsulated in MOFs. More interestingly, the trend of activity change is consistent with our previous work on catalytic sites generated in situ from Pd(II) coordinated in MOFs bearing the same functional groups, which suggests that both MOF-Pd NPs and MOF-Pd(II) catalysts generate similar active centers during Suzuki–Miyaura coupling reactions. Lastly, this work paves a new avenue to the fabrication of advanced and tunable MOF-based catalysts through rational linker engineering.« less

Unveiling the Effects of Linker Substitution in Suzuki Coupling with Palladium Nanoparticles in Metal–Organic Frameworks [Unveiling the Effects of Linker Substitution in Suzuki Coupling Reaction with Palladium Nanoparticles in Metal–Organic Frameworks

DOE PAGES

Li, Xinle; Zhang, Biying; Van Zeeland, Ryan; ...

2018-01-18

The establishment of structure–property relationships in heterogeneous catalysis is of prime importance but remains a formidable challenge. Metal–organic frameworks (MOFs) featuring excellent chemical tunability are emerging as an auspicious platform for the atomic-level control of heterogeneous catalysis. Herein, we encapsulate palladium nanoparticles (Pd NPs) in a series of isoreticular mixed-linker MOFs, and the obtained MOF-Pd NPs catalysts were used to unveil the electronic and steric effects of linker substitution on the activity of these catalysts in the Suzuki–Miyaura cross-coupling reactions. Significantly, m-6,6'-Me2bpy-MOF-Pd exhibits a remarkable enhancement in the activity compared to non-functionalized m-bpy-MOF-Pd and m-4,4'-Me 2bpy-MOF-Pd. This study unambiguously demonstratesmore » that the stereoelectronic properties of linker units are crucial to the catalytic activity of nanoparticles encapsulated in MOFs. More interestingly, the trend of activity change is consistent with our previous work on catalytic sites generated in situ from Pd(II) coordinated in MOFs bearing the same functional groups, which suggests that both MOF-Pd NPs and MOF-Pd(II) catalysts generate similar active centers during Suzuki–Miyaura coupling reactions. Lastly, this work paves a new avenue to the fabrication of advanced and tunable MOF-based catalysts through rational linker engineering.« less

Highly functionalized biaryls via Suzuki-Miyaura cross-coupling catalyzed by Pd@MOF under batch and continuous flow regimes.

PubMed

Pascanu, Vlad; Hansen, Peter R; Bermejo Gómez, Antonio; Ayats, Carles; Platero-Prats, Ana E; Johansson, Magnus J; Pericàs, Miquel À; Martín-Matute, Belén

2015-01-01

A diverse set of more than 40 highly functionalized biaryls was synthesized successfully through the Suzuki-Miyaura cross-coupling reaction catalyzed by Pd nanoparticles supported in a functionalized mesoporous MOF (8 wt % Pd@MIL-101(Cr)-NH2 ). This could be achieved under some of the mildest conditions reported to date and a strong control over the leaching of metallic species could be maintained, despite the presence of diverse functional groups and/or several heteroatoms. Some of the targeted molecules are important intermediates in the synthesis of pharmaceuticals and we clearly exemplify the versatility of this catalytic system, which affords better yields than currently existing commercial procedures. Most importantly, Pd@MIL-101-NH2 was packed in a micro-flow reactor, which represents the first report of metallic nanoparticles supported on MOFs employed in flow chemistry for catalytic applications. A small library of 11 isolated compounds was created in a continuous experiment without replacing the catalyst, demonstrating the potential of the catalyst for large-scale applications. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The Suzuki-Miyaura Cross-Coupling Reaction of Halogenated Aminopyrazoles: Method Development, Scope, and Mechanism of Dehalogenation Side Reaction.

PubMed

Jedinák, Lukáš; Zátopková, Renáta; Zemánková, Hana; Šustková, Alena; Cankař, Petr

2017-01-06

The efficient Suzuki-Miyaura cross-coupling reaction of halogenated aminopyrazoles and their amides or ureas with a range of aryl, heteroaryl, and styryl boronic acids or esters has been developed. The method allowed incorporation of problematic substrates: aminopyrazoles bearing protected or unprotected pyrazole NH, as well as the free amino or N-amide group. Direct comparison of the chloro, bromo, and iodopyrazoles in the Suzuki-Miyaura reaction revealed that Br and Cl derivatives were superior to iodopyrazoles, as a result of reduced propensity to dehalogenation. Moreover, the mechanism and factors affecting the undesired dehalogenation side reaction were revealed.

Click ionic liquids: a family of promising tunable solvents and application in Suzuki-Miyaura cross-coupling.

PubMed

Li, Liuyi; Wang, Jinyun; Wu, Tao; Wang, Ruihu

2012-06-18

A series of click ionic salts 4 a-4 n was prepared through click reaction of organic azides with alkyne-functionalized imidazolium or 2-methylimidazolium salts, followed by metathesis with lithium bis(trifluoromethanesulfonyl)amide or potassium hexafluorophosphate. All salts were characterized by IR, NMR, TGA, and DSC, and most of them can be classified as ionic liquids. Their steric and electronic properties can be easily tuned and modified through variation of the aromatic or aliphatic substituents at the imidazolium and/or triazolyl rings. The effect of anions and substituents at the two rings on the physicochemical properties was investigated. The charge and orbital distributions based on the optimized structures of cations in the salts were calculated. Reaction of 4 a with PdCl(2) produced mononuclear click complex 4 a-Pd, the structure of which was confirmed by single-crystal X-ray diffraction analysis. Suzuki-Miyaura cross-coupling shows good catalytic stability and high recyclability in the presence of PdCl(2) in 4 a. TEM and XPS analyses show formation of palladium nanoparticles after the reaction. The palladium NPs in 4 a are immobilized by the synergetic effect of coordination and electrostatic interactions with 1,2,3-triazolyl and imidazolium, respectively. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A convergent approach to the total synthesis of telmisartan via a Suzuki cross-coupling reaction between two functionalized benzimidazoles.

PubMed

Martin, Alex D; Siamaki, Ali R; Belecki, Katherine; Gupton, B Frank

2015-02-06

A direct and efficient total synthesis has been developed for telmisartan, a widely prescribed treatment for hypertension. This approach brings together two functionalized benzimidazoles using a high-yielding Suzuki reaction that can be catalyzed by either a homogeneous palladium source or graphene-supported palladium nanoparticles. The ability to perform the cross-coupling reaction was facilitated by the regio-controlled preparation of the 2-bromo-1-methylbenzimidazole precursor. This convergent approach provides telmisartan in an overall yield of 72% while circumventing many issues associated with previously reported processes.

Suzuki-Miyaura Cross-Coupling Reactions of Primary Alkyltrifluoroborates with Aryl Chlorides

PubMed Central

Dreher, Spencer D.; Lim, Siang-Ee; Sandrock, Deidre L.; Molander, Gary A.

2009-01-01

Parallel microscale experimentation was used to develop general conditions for the Suzuki-Miyaura cross-coupling of diversely functionalized primary alkyltrifluoroborates with a variety of aryl chlorides. These conditions were found to be amenable to coupling with aryl bromides, iodides, and triflates as well. The conditions that were previously identified through similar techniques to promote the cross-coupling of secondary alkyltrifluoroborates with aryl chlorides were not optimal for the primary alkyltrifluoroborates, thus demonstrating the value of parallel experimentation to develop novel, substrate specific results. PMID:19271726

Remarkable co-catalysis by copper(I) oxide in the palladium catalyzed cross-coupling of arylboronic acids with ethyl bromoacetate.

PubMed

Liu, Xing-xin; Deng, Min-zhi

2002-03-21

Copper(I) oxide can effectively co-catalyze the Suzuki type cross-coupling reactions of arylboronic acids with ethyl bromoacetate. As an alternative protocol for introducing the methylenecarboxy group into functionalized molecules, this reaction occurs in the absence of highly toxic thallium compounds or special ligands and should be convenient and practical.

Construction of 1-Heteroaryl-3-azabicyclo[3.1.0]hexanes by sp3-sp2 Suzuki-Miyaura and Chan-Evans-Lam Coupling Reactions of Tertiary Trifluoroborates.

PubMed

Harris, Michael R; Li, Qifang; Lian, Yajing; Xiao, Jun; Londregan, Allyn T

2017-05-05

Compounds that contain the 1-heteroaryl-3-azabicyclo[3.1.0]hexane architecture are of particular interest to the pharmaceutical industry yet remain a challenge to synthesize. We report herein an expedient and modular approach to the synthesis of 1-heteroaryl-3-azabicyclo[3.1.0]hexanes by Suzuki-Miyaura and Chan-Evans-Lam coupling reactions of tertiary trifluoroborate salts. Our Suzuki-Miyaura cross-coupling protocol is compatible with a broad range of aryl and heteroaryl bromides and chlorides. The unprecedented Chan-Evans-Lam coupling of tertiary trifluoroborates allows the facile construction of 1-heteroaryl-3-azabicyclo[3.1.0]hexanes containing C-tertiary arylamines at the ring juncture.

Asymmetric Suzuki-Miyaura coupling of heterocycles via Rhodium-catalysed allylic arylation of racemates

PubMed Central

Schäfer, Philipp; Palacin, Thomas; Sidera, Mireia; Fletcher, Stephen P.

2017-01-01

Using asymmetric catalysis to simultaneously form carbon–carbon bonds and generate single isomer products is strategically important. Suzuki-Miyaura cross-coupling is widely used in the academic and industrial sectors to synthesize drugs, agrochemicals and biologically active and advanced materials. However, widely applicable enantioselective Suzuki-Miyaura variations to provide 3D molecules remain elusive. Here we report a rhodium-catalysed asymmetric Suzuki-Miyaura reaction with important partners including aryls, vinyls, heteroaromatics and heterocycles. The method can be used to couple two heterocyclic species so the highly enantioenriched products have a wide array of cores. We show that pyridine boronic acids are unsuitable, but they can be halogen-modified at the 2-position to undergo reaction, and this halogen can then be removed or used to facilitate further reactions. The method is used to synthesize isoanabasine, preclamol, and niraparib—an anticancer agent in several clinical trials. We anticipate this method will be a useful tool in drug synthesis and discovery. PMID:28607510

Asymmetric Suzuki-Miyaura coupling of heterocycles via Rhodium-catalysed allylic arylation of racemates

NASA Astrophysics Data System (ADS)

Schäfer, Philipp; Palacin, Thomas; Sidera, Mireia; Fletcher, Stephen P.

2017-06-01

Using asymmetric catalysis to simultaneously form carbon-carbon bonds and generate single isomer products is strategically important. Suzuki-Miyaura cross-coupling is widely used in the academic and industrial sectors to synthesize drugs, agrochemicals and biologically active and advanced materials. However, widely applicable enantioselective Suzuki-Miyaura variations to provide 3D molecules remain elusive. Here we report a rhodium-catalysed asymmetric Suzuki-Miyaura reaction with important partners including aryls, vinyls, heteroaromatics and heterocycles. The method can be used to couple two heterocyclic species so the highly enantioenriched products have a wide array of cores. We show that pyridine boronic acids are unsuitable, but they can be halogen-modified at the 2-position to undergo reaction, and this halogen can then be removed or used to facilitate further reactions. The method is used to synthesize isoanabasine, preclamol, and niraparib--an anticancer agent in several clinical trials. We anticipate this method will be a useful tool in drug synthesis and discovery.

Synthesis of novel carbazole derived substances using some organoboron compounds by palladium catalyzed and investigation of its semiconductor device characteristics

NASA Astrophysics Data System (ADS)

Gorgun, Kamuran; Caglar, Yasemin

2018-04-01

Carbazole compounds in particular represent one of the most intensely used and studied class of semiconducting materials. In this study, considering the information given in the literature the Ullman and Suzuki-Miyaura coupling reaction were carried out using carbazole, 1,4-dibromobenzene and pyrene-1-boronic acid. The synthesized carbazole derivatives are characterized by 1H NMR and elemental analysis. The spectroscopic and thermal properties of the synthesized novel carbazole derivative 9-(4-(pyren-4-yl)phenyl)-9H-carbazole (Cz-py) were investigated. And also, the n-Si/p-Cz:py heterojunction diode was fabricated. The electrical properties of this diode were characterized by current-voltage (I-V) and capacitance-voltage (C-V) measurements.

Palladium-Catalyzed α-Arylation of 2-Chloroacetates and 2-Chloroacetamides

PubMed Central

Traister, Kaitlin M.; Barcellos, Thiago

2013-01-01

A method has been developed for the Pd-catalyzed synthesis of α-(hetero)aryl esters and amides through a Suzuki–Miyaura cross-coupling reaction. This method avoids the use of strong base, does not necessitate inert or low temperature formation of reagents, and does not require the use of a large excess of organometallic reagent. Utilization of organotrifluoroborate salts as nucleophilic partners allows a variety of functional groups and heterocyclic compounds to be tolerated. PMID:23570264

Ortho Group Activation of a Bromopyrrole Ester in Suzuki-Miyaura Cross-Coupling Reactions: Application to the Synthesis of New Microtubule Depolymerizing Agents with Potent Cytotoxic Activities

PubMed Central

Gupton, John T.; Yeudall, Scott; Telang, Nakul; Hoerrner, Megan; Huff, Ellis; Crawford, Evan; Lounsbury, Katie; Kimmel, Michael; Curry, William; Harrison, Andrew; Juekun, Wen; Shimozono, Alex; Ortolani, Joe; Lescalleet, Kristin; Patteson, Jon; Moore-Stoll, Veronica; Rohena, Cristina C.; Mooberry, Susan L.; Obaidullah, Ahmad J.; Kellogg, Glen E.; Sikorski, James A.

2017-01-01

New microtubule depolymerizing agents with potent cytotoxic activities have been prepared with a 5-cyano or 5-oximino group attached to a pyrrole core. The utilization of ortho activation of a bromopyrrole ester to facilitate successful Suzuki-Miyaura cross-coupling reactions was a key aspect of the synthetic methodology. This strategy allows for control of regiochemistry with the attachment of four completely different groups at the 2, 3, 4 and 5 positions of the pyrrole scaffold. Biological evaluations and molecular modeling studies are reported for these examples. PMID:28433513

Palladium-catalyzed domino C,N-coupling/carbonylation/Suzuki coupling reaction: an efficient synthesis of 2-aroyl-/heteroaroylindoles.

PubMed

Arthuis, Martin; Pontikis, Renée; Florent, Jean-Claude

2009-10-15

A convenient one-pot synthesis of 2-aroylindoles using a domino palladium-catalyzed C,N-coupling/carbonylation/C,C-coupling sequence is described. The reaction involved easily prepared 2-gem-dibromovinylanilines and boronic acids under carbon monoxide. Optimized reaction conditions allowed the construction of a wide variety of highly functionalized 2-aroyl-/heteroaroylindoles in satisfactory yields.

Mechanistic Investigation of Catalyst-Transfer Suzuki-Miyaura Condensation Polymerization of Thiophene-Pyridine Biaryl Monomers with the Aid of Model Reactions.

PubMed

Tokita, Yu; Katoh, Masaru; Ohta, Yoshihiro; Yokozawa, Tsutomu

2016-11-21

We have investigated the requirements for efficient Pd-catalyzed Suzuki-Miyaura catalyst-transfer condensation polymerization (Pd-CTCP) reactions of 2-alkoxypropyl-6-(5-bromothiophen-2-yl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (12) as a donor-acceptor (D-A) biaryl monomer. As model reactions, we first carried out the Suzuki-Miyaura coupling reaction of X-Py-Th-X' (Th=thiophene, Py=pyridine, X, X'=Br or I) 1 with phenylboronic acid ester 2 by using tBu 3 PPd 0 as the catalyst. Monosubstitution with a phenyl group at Th-I mainly took place in the reaction of Br-Py-Th-I (1 b) with 2, whereas disubstitution selectively occurred in the reaction of I-Py-Th-Br (1 c) with 2, indicating that the Pd catalyst is intramolecularly transferred from acceptor Py to donor Th. Therefore, we synthesized monomer 12 by introduction of a boronate moiety and bromine into Py and Th, respectively. However, examination of the relationship between monomer conversion and the M n of the obtained polymer, as well as the matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectra, indicated that Suzuki-Miyaura coupling polymerization of 12 with (o-tolyl)tBu 3 PPdBr initiator 13 proceeded in a step-growth polymerization manner through intermolecular transfer of the Pd catalyst. To understand the discrepancy between the model reactions and polymerization reaction, Suzuki-Miyaura coupling reactions of 1 c with thiopheneboronic acid ester instead of 2 were carried out. This resulted in a decrease of the disubstitution product. Therefore, step-growth polymerization appears to be due to intermolecular transfer of the Pd catalyst from Th after reductive elimination of the Th-Pd-Py complex formed by transmetalation of polymer Th-Br with (Pin)B-Py-Th-Br monomer 12 (Pin=pinacol). Catalysts with similar stabilization energies of metal-arene η 2 -coordination for D and A monomers may be needed for CTCP reactions of biaryl D-A monomers. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Syntheses of the hexahydroindene cores of indanomycin and stawamycin by combinations of iridium-catalyzed asymmetric allylic alkylations and intramolecular Diels-Alder reactions.

PubMed

Gärtner, Martin; Satyanarayana, Gedu; Förster, Sebastian; Helmchen, Günter

2013-01-02

Short and concise syntheses of the hexahydroindene cores of the antibiotics indanomycin (X-14547 A) and stawamycin are presented. Key methods used are an asymmetric iridium-catalyzed allylic alkylation, a modified Julia olefination, a Suzuki-Miyaura coupling, and an intramolecular Diels-Alder reaction. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Heteroaryl ethers by oxidative palladium catalysis of pyridotriazol-1-yloxy pyrimidines with arylboronic acids.

PubMed

Bardhan, Sujata; Wacharasindhu, Sumrit; Wan, Zhao-Kui; Mansour, Tarek S

2009-06-18

The oxidative palladium-catalyzed cross-coupling of pyrimidines containing pyridotriazol-1-yloxy (OPt) as either a urea or an amide functional group with arylboronic acids in the presence of Cs(2)CO(3) in DME containing 0.6-1.0% H(2)O is described for the preparation of heteroaryl ethers. The bromo substitution in the case of 3-(5-bromo-pyrimidin-2-yloxy)-3H-[1,2,3]triazolo[4,5-b]pyridine 1 could serve as a handle for further elaborations such as Suzuki coupling for attaching varied aryl groups.

Palladium coupling catalysts for pharmaceutical applications.

PubMed

Doucet, Henri; Hierso, Jean-Cyrille

2007-11-01

This review discusses recent advances made in the area of palladium-catalyzed coupling reactions and describes a selection of the catalytic systems that are useful in the preparation of valuable compounds for the pharmaceutical industry. Most of these types of syntheses have used either simple palladium salts or palladium precursors associated with electron-rich mono- or bidentate phosphine ligands as catalysts. For some reactions, ligands such as triphenyl phosphine, 1,1'-bis(diphenylphosphino)ferrocene, a carbene or a bipyridine have also been employed. Several new procedures for the Suzuki cross-coupling reaction, the activation of aryl chlorides, the functionalization of aromatics and the synthesis of heteroaromatics are discussed. The C-H activation/ functionalization reactions of aryl and heteroaryl derivatives have emerged as powerful tools for the preparation of biaryl compounds, and the recent procedures and catalysts employed in this promising field are also highlighted herein.

Facile synthesis of multisubstituted buta-1,3-dienes via Suzuki-Miyaura and Kumada cross-coupling strategy of 2,4-diiodo-buta-1-enes with arylboronic acids and Grignard reagents.

PubMed

Shao, Li-Xiong; Shi, Min

2005-05-21

One-pot Suzuki-Miyaura-type and Kumada-type cross-coupling reactions of 2,4-diiodo-buta-1-enes with arylboronic acids and alkyl/aryl magnesium bromides were carried out in the presence of accessibly simple catalysts under mild conditions. As a result, some 1,1,2-trisubstituted buta-1,3-dienes were obtained including the Tamoxifen-type, which have potential adjuvant therapy in women who have suffered from breast cancer and cyclooxygenase-2-type (COX-2-type) inhibitors, some of which have been proved to elicit efficient anti-inflammatory analgesic activities and less adverse gastrointestinal side effects and to be very useful in the prophylactic treatment of a wide variety of cancers and neurodegenerative disorders.

Biscarbene palladium(II) complexes. reactivity of saturated versus unsaturated N-heterocyclic carbenes.

PubMed

Fu, Ching-Feng; Lee, Chun-Chin; Liu, Yi-Hung; Peng, Shie-Ming; Warsink, Stefan; Elsevier, Cornelis J; Chen, Jwu-Ting; Liu, Shiuh-Tzung

2010-03-15

A series of designed palladium biscarbene complexes including saturated and unsaturated N-heterocyclic carbene (NHC) moieties have been prepared by the carbene transfer methods. All of these complexes have been characterized by (1)H and (13)C NMR spectroscopy as well as X-ray diffraction analysis. The reactivity of Pd-C((saturated NHC)) is distinct from that of Pd-C((unsaturated NHC)). The Pd-C((saturated NHC)) bonds are fairly stable toward reagents such as CF(3)COOH, AgBF(4) and I(2), whereas Pd-C((unsaturated NHC)) bonds are readily cleaved under the similar conditions. Notably, the catalytically activity of these palladium complexes on Suzuki-Miyaura coupling follows the order: (sat-NHC)(2)PdCl(2) > (sat-NHC)(unsat-NHC)PdCl(2 )> (unsat-NHC)(2)PdCl(2).

The Introduction of High-Throughput Experimentation Methods for Suzuki-Miyaura Coupling Reactions in University Education

ERIC Educational Resources Information Center

Hoogenboom, Richard; Meier, Michael A. R.; Schubert, Ulrich S.

2005-01-01

A laboratory project permits for the discussion of the reaction mechanism of the Suzuki-Miyaura coupling reaction. The practical part of the project makes the students familiar with working under inert atmosphere but if the appropriate equipment for working under inert atmosphere is not available in a laboratory, novel catalysts that do not…

Resin-Immobilized Palladium Nanoparticle Catalysts for Organic Reactions in Aqueous Media: Morphological Aspects.

PubMed

Mastrorilli, Piero; Dell'Anna, Maria M; Rizzuti, Antonino; Mali, Matilda; Zapparoli, Mauro; Leonelli, Cristina

2015-10-14

An insight into the nano- and micro-structural morphology of a polymer supported Pd catalyst employed in different catalytic reactions under green conditions is reported. The pre-catalyst was obtained by copolymerization of the metal-containing monomer Pd(AAEMA)₂ [AAEMA-=deprotonated form of 2-(acetoacetoxy) ethyl methacrylate] with ethyl methacrylate as co-monomer, and ethylene glycol dimethacrylate as cross-linker. This material was used in water for the Suzuki-Miyaura cross-coupling of aryl bromides, and for the reduction of nitroarenes and quinolines using NaBH₄ or H₂, as reductants. TEM analyses showed that in all cases the pristine Pd(II) species were reduced in situ to Pd(0), which formed metal nanoparticles (NPs, the real active species). The dependence of their average size (2-10 nm) and morphology on different parameters (temperature, reducing agent, presence of a phase transfer agent) is discussed. TEM and micro-IR analyses showed that the polymeric support retained its porosity and stability for several catalytic cycles in all reactions and Pd NPs did not aggregate after reuse. The metal nanoparticle distribution throughout the polymer matrix after several recycles provided precious information about the catalytic mechanism, which was truly heterogeneous in the hydrogenation reactions and of the so-called "release and catch" type in the Suzuki coupling.

Photoinduced Miyaura Borylation by a Rare Earth Photoreductant: the Hexachlorocerate(III) Anion.

PubMed

Qiao, Yusen; Yang, Qiaomu; Schelter, Eric

2018-05-12

The first photoinduced sp2 carbon-heteroatom bond forming reaction by a rare earth photoreductant, a Miyaura borylation, has been achieved. This simple, scalable, and novel borylation method that makes use of the hexachlorocerate(III) anion, [CeIIICl6]3-, has a broad substrate scope and functional group tolerance and can be conducted at room temperature. Combined with Suzuki-Miyaura cross-coupling, the methodology is applicable to the synthesis of various biaryl products, including through the use of aryl chloride substrates. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Weakly nucleophilic potassium aryltrifluoroborates in palladium-catalyzed Suzuki-Miyaura reactions: relative reactivity of K[4-RC6F4BF3] and the role of silver-assistance in acceleration of transmetallation.

PubMed

Bardin, Vadim V; Shabalin, Anton Yu; Adonin, Nicolay Yu

2015-01-01

Small differences in the reactivity of weakly nucleophilic potassium aryltrifluoroborates are revealed in the silver-assisted Pd-catalyzed cross-coupling of K[4-RC6F4BF3] (R = H, Bu, MeO, EtO, PrO, iPrO, BuO, t-BuO, CH2=CHCH2O, PhCH2O, PhCH2CH2O, PhO, F, pyrazol-1-yl, pyrrol-1-yl, and indol-1-yl) with ArX (4-BrC6H4CH3, 4-IC6H4F and 3-IC6H4F). An assumed role of silver(I) compounds Ag m Y (Y = O, NO3, SO4, BF4, F) consists in polarization of the Pd-X bond in neutral complex ArPdL n X with the generation of the related transition state or formation of [ArPdL n ][XAg m Y] with a highly electrophilic cation and subsequent transmetallation with the weakly nucleophilic borate. Efficiency of Ag m Y as a polarizing agent decreases in order Ag2O > AgNO3 ≈ Ag2SO4 > Ag[BF4] > AgF. No clear correlation between the reactivity of K[4-RC6F4BF3] and substituent electron parameters, σI and σR°, of the aryl group 4-RC6F4 was found.

Pd(II) and Pt(II) complexes of α-keto stabilized sulfur ylide: Synthesis, structural, theoretical and catalytic activity studies

NASA Astrophysics Data System (ADS)

Sabounchei, Seyyed Javad; Hashemi, Ali; Sedghi, Asieh; Bayat, Mehdi; Akhlaghi Bagherjeri, Fateme; Gable, Robert W.

2017-05-01

Reaction of dimethyl sulfide with 2, 3‧-dibromoacetophenone led to formation of sulfonium salt [Me2SCH2C(O)C6H4-m-Br]Br (1). The resulted sulfonium salt was treated with NaOH and gave the α-keto stabilized sulfur ylide Me2SC(H)C(O)C6H4-m-Br (2). This ligand was reacted with [MCl2(cod)] (M = Pd, Pt; cod = 1,5-cyclooctadiene) to form the new cis- and trans-[MCl2(ylide)2] (M = Pd (cis- and trans-3), Pt (cis- and trans-4)) complexes. Characterization of the obtained compounds was performed by elemental analysis, IR, 1H and 13C NMR. Recrystallization of dichlorobis(ylide) palladium(II) and platinum(II) complexes from DMSO solution yielded the crystalline products, which X-ray diffraction data revealed that the both compounds were crystallized as cis-[MCl2(ylide)(DMSO)] (M = Pd (5), Pt (6)) complexes. Also, a theoretical study on structure and nature of the Msbnd C bonding between the Y ligand (ylide) and [MCl2·DMSO] fragments in [YMCl2·DMSO] (M = Pd, Pt) complexes has been reported via NBO and energy-decomposition analysis (EDA). Furthermore, the palladium catalyzed Suzuki-Miyaura reaction of various aryl chlorides with arylboronic acids was performed. The results showed that the Pd(II) complexes cis- and trans-3 catalyzed efficiently coupling reactions at low catalyst loading and short reaction time.

Synthesis and conformational analysis of new arylated-diphenylurea derivatives related to sorafenib drug via Suzuki-Miyaura cross-coupling reaction

NASA Astrophysics Data System (ADS)

Al-Masoudi, Najim A.; Essa, Ali Hashem; Alwaaly, Ahmed A. S.; Saeed, Bahjat A.; Langer, Peter

2017-10-01

Sorafenib, is a relatively new cytostatic drug approved for the treatment of renal cell and hepatocellular carcinoma. The development of new sorafenib analogues offers the possibility of generating structures of increased potency. To this end, a series of arylated-diphenylurea analogues 17-31 were synthesized via Suzuki-Miyaura coupling reaction, related to sorafenib by treatment of three diarylureas 2-4 having 3-bromo, 4-chloro and 2-iodo groups with various arylboronic acids. Conformational analysis of the new arylated urea analogues has been investigated using MOPAC 2016 of semi empirical PM7 Hamiltonian computational method. Our results showed that all compounds preferred the trans-trans conformations. Compound 17 has been selected to calculate the torsional energy profiles for rotation around the urea bonds and found to be existed predominantly in the trans-trans conformation with only very minimal fluctuation in conformation.

Synthesis of (+)-Antroquinonol: An Antihyperglycemic Agent.

PubMed

Sulake, Rohidas S; Lin, Hsiao-Han; Hsu, Chia-Yu; Weng, Ching-Feng; Chen, Chinpiao

2015-06-19

The total synthesis of antroquinonol has been accomplished through Suzuki-Miyaura cross-coupling and Barton-McCombie reaction, and the α,β-unsaturation was achieved through selenylation and oxidation protocols. In vitro and in vivo studies on the glucose-lowering properties of antroquinonol indicate that it is a potential antidiabetic agent.

2,2'-Biphenols via protecting group-free thermal or microwave-accelerated Suzuki-Miyaura coupling in water.

PubMed

Schmidt, Bernd; Riemer, Martin; Karras, Manfred

2013-09-06

User-friendly protocols for the protecting group-free synthesis of 2,2'-biphenols via Suzuki-Miyaura coupling of o-halophenols and o-boronophenol are presented. The reactions proceed in water in the presence of simple additives such as K2CO3, KOH, KF, or TBAF and with commercially available Pd/C as precatalyst. Expensive or laboriously synthesized ligands or other additives are not required. In the case of bromophenols, efficient rate acceleration and short reaction times were accomplished by microwave irradiation.

Pd(0)-CMC@Ce(OH)(4) organic/inorganic hybrid as highly active catalyst for the Suzuki-Miyaura reaction.

PubMed

Lin, Bijin; Liu, Xiaoping; Zhang, Zhuan; Chen, Yang; Liao, Xiaojian; Li, Yiqun

2017-07-01

A very easy sequential metathesis for the synthesis of Pd(II)-CMC@Ce(OH) 4 organic/inorganic hybrid and its application as effective pre-catalyst for the Suzuki-Miyaura reaction have been reported. It was found that the Pd nanoparticles (Pd NPs) were formed in situ in the course of the Suzuki-Miyaura couplings when Pd(II)-CMC@Ce(OH) 4 was used as a pre-catalyst. The activity of the Pd NPs in the reaction was enhanced synergistically by the unique redox properties (Ce 3+ /Ce 4+ ) of Ce(OH) 4 and coordination with carboxyl groups as well as free hydroxyl groups of the hybrid of CMC@Ce(OH) 4 . The results exhibit the Pd(0)-CMC@Ce(OH) 4 is super over Pd(II)@CMC, Pd(II)@CeO 2 , and Pd(II)@Ce(OH) 4 catalysts in the Suzuki-Miyaura reaction. Moreover, the catalyst could be easily separated by simple filtration and reused at least seven runs without losing its activity. Copyright © 2017 Elsevier Inc. All rights reserved.

Automated synthesis of a 184-member library of thiadiazepan-1,1-dioxide-4-ones.

PubMed

Fenster, Erik; Long, Toby R; Zang, Qin; Hill, David; Neuenswander, Benjamin; Lushington, Gerald H; Zhou, Aihua; Santini, Conrad; Hanson, Paul R

2011-05-09

The construction of a 225-member (3 × 5 × 15) library of thiadiazepan-1,1-dioxide-4-ones was performed on a Chemspeed Accelerator (SLT-100) automated parallel synthesis platform, culminating in the successful preparation of 184/225 sultams. Three sultam core scaffolds were prepared based upon the utilization of an aza-Michael reaction on a multifunctional vinyl sulfonamide linchpin. The library exploits peripheral diversity in the form of a sequential, two-step [3 + 2] Huisgen cycloaddition/Pd-catalyzed Suzuki-Miyaura coupling sequence.

Efficient Synthesis of Novel Pyridine-Based Derivatives via Suzuki Cross-Coupling Reaction of Commercially Available 5-Bromo-2-methylpyridin-3-amine: Quantum Mechanical Investigations and Biological Activities.

PubMed

Ahmad, Gulraiz; Rasool, Nasir; Ikram, Hafiz Mansoor; Gul Khan, Samreen; Mahmood, Tariq; Ayub, Khurshid; Zubair, Muhammad; Al-Zahrani, Eman; Ali Rana, Usman; Akhtar, Muhammad Nadeem; Alitheen, Noorjahan Banu

2017-01-27

The present study describes palladium-catalyzed one pot Suzuki cross-coupling reaction to synthesize a series of novel pyridine derivatives 2a - 2i , 4a - 4i . In brief, Suzuki cross-coupling reaction of 5-bromo-2-methylpyridin-3-amine ( 1 ) directly or via N -[5-bromo-2-methylpyridine-3-yl]acetamide ( 3 ) with several arylboronic acids produced these novel pyridine derivatives in moderate to good yield. Density functional theory (DFT) studies were carried out for the pyridine derivatives 2a - 2i and 4a - 4i by using B3LYP/6-31G(d,p) basis with the help of GAUSSIAN 09 suite programme. The frontier molecular orbitals analysis, reactivity indices, molecular electrostatic potential and dipole measurements with the help of DFT methods, described the possible reaction pathways and potential candidates as chiral dopants for liquid crystals. The anti-thrombolytic, biofilm inhibition and haemolytic activities of pyridine derivatives were also investigated. In particular, the compound 4b exhibited the highest percentage lysis value (41.32%) against clot formation in human blood among all newly synthesized compounds. In addition, the compound 4f was found to be the most potent against Escherichia coli with an inhibition value of 91.95%. The rest of the pyridine derivatives displayed moderate biological activities.

The marriage of metallacycle transfer chemistry with Suzuki-Miyaura cross-coupling to give main group element-containing conjugated polymers.

PubMed

He, Gang; Kang, Le; Torres Delgado, William; Shynkaruk, Olena; Ferguson, Michael J; McDonald, Robert; Rivard, Eric

2013-04-10

A versatile and general synthetic route for the synthesis of conjugated main group element-based polymers, previously inaccessible by conventional means, is reported. These polymers contain five-membered chalcogenophene rings based on S, Se, and Te, and we demonstrate that optoelectronic properties can be readily tuned via controlled atom substitution chemistry. In addition, regioregular hybrid thiophene-selenophene-tellurophene and selenophene-fluorene copolymers were synthesized to provide a further illustration of the scope of the presented metallacycle transfer/cross-coupling polymerization method.

Living GenoChemetics by hyphenating synthetic biology and synthetic chemistry in vivo.

PubMed

Sharma, Sunil V; Tong, Xiaoxue; Pubill-Ulldemolins, Cristina; Cartmell, Christopher; Bogosyan, Emma J A; Rackham, Emma J; Marelli, Enrico; Hamed, Refaat B; Goss, Rebecca J M

2017-08-09

Marrying synthetic biology with synthetic chemistry provides a powerful approach toward natural product diversification, combining the best of both worlds: expediency and synthetic capability of biogenic pathways and chemical diversity enabled by organic synthesis. Biosynthetic pathway engineering can be employed to insert a chemically orthogonal tag into a complex natural scaffold affording the possibility of site-selective modification without employing protecting group strategies. Here we show that, by installing a sufficiently reactive handle (e.g., a C-Br bond) and developing compatible mild aqueous chemistries, synchronous biosynthesis of the tagged metabolite and its subsequent chemical modification in living culture can be achieved. This approach can potentially enable many new applications: for example, assay of directed evolution of enzymes catalyzing halo-metabolite biosynthesis in living cells or generating and following the fate of tagged metabolites and biomolecules in living systems. We report synthetic biological access to new-to-nature bromo-metabolites and the concomitant biorthogonal cross-coupling of halo-metabolites in living cultures.Coupling synthetic biology and chemical reactions in cells is a challenging task. The authors engineer bacteria capable of generating bromo-metabolites, develop a mild Suzuki-Miyaura cross-coupling reaction compatible with cell growth and carry out the cross-coupling chemistry in live cell cultures.

A Facile Synthesis of Blue Luminescent [7]Helicenocarbazoles Based on Gold-Catalyzed Rearrangement-Iodonium Migration and Suzuki-Miyaura Benzannulation Reactions.

PubMed

Alcaide, Benito; Almendros, Pedro; Aragoncillo, Cristina; Busto, Eduardo; López-Calixto, Carmen G; Liras, Marta; de la Peña O'Shea, Víctor A; García-Sánchez, Alba; Stone, Hannah V

2018-05-28

New azahelicenes having interesting photophysical properties have been prepared in a four-step sequence. These [7]helicenocarbazoles are efficient blue luminophores, demonstrating the utility of gold catalysis in the preparation of advanced materials. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Construction of hierarchically porous monoliths from covalent organic frameworks (COFs) and their application for bisphenol A removal.

PubMed

Liu, Zhongshan; Wang, Hongwei; Ou, Junjie; Chen, Lianfang; Ye, Mingliang

2018-05-11

Subject to synthetic conditions, covalent organic frameworks (COFs) are usually in powder form. Herein, taking an azine-linked COF as an example, detailed characterizations indicated that accessible aldehyde groups and hydrazine groups (CNNH 2 , 88 μmol g -1 ) concurrently existed on its surface. Intrigued by such feature, we have developed an approach based on ring-opening polymerization to shape COF powder into monoliths. The crystallinity and micropore of COF in monoliths were well remained, meanwhile, the ring-opening polymerization remarkably generated macropores ranging from 0.43 to 3.51 μm, indicating a hierarchically porous structure. The BET surface area of resultant monoliths with different COF mass fractions of 16%, 28% and 43% ranged from 105 to 281 m 2  g -1 . Due to the π-π interaction and hydrogen bond interaction, COF-based monoliths exhibited strong retention and rapid adsorption for bisphenol A (BPA) in aqueous medium. When 29 mL BPA solution (22.8 mg L -1 ) passed through COF-based monolith (28%), the adsorption capacity was up to 61.3 mg g -1 . Furthermore, the COF-based monolith demonstrated excellent cycle use for catalyzing Suzuki-Miyaura coupling reaction after being coordinated with palladium acetate. Copyright © 2018 Elsevier B.V. All rights reserved.

Preparation, structural characterization, and catalytic performance of Pd(II) and Pt(II) complexes derived from cellulose Schiff base

NASA Astrophysics Data System (ADS)

Baran, Talat; Yılmaz Baran, Nuray; Menteş, Ayfer

2018-05-01

In this study, we reported production, characterization, and catalytic behavior of two novel heterogeneous palladium(II) and platinum(II) catalysts derived from cellulose biopolymer. In order to eliminate the use of toxic organic or inorganic solvents and to reduce the use of excess energy in the coupling reactions, we have developed a very simple, rapid, and eco-friendly microwave irradiation protocol. The developed microwave-assisted method of Suzuki cross coupling reactions produced excellent reaction yields in the presence of cellulose supported palladium and platinum (II) catalysts. Moreover, the catalysts easily regenerated after simple filtration, and they gave good reusability. This study revealed that the designed catalysts and method provide clean, simple, rapid, and impressive catalytic performance for Suzuki coupling reactions.

Heterogeneous Pd catalysts as emulsifiers in Pickering emulsions for integrated multistep synthesis in flow chemistry.

PubMed

Hiebler, Katharina; Lichtenegger, Georg J; Maier, Manuel C; Park, Eun Sung; Gonzales-Groom, Renie; Binks, Bernard P; Gruber-Woelfler, Heidrun

2018-01-01

Within the "compartmentalised smart factory" approach of the ONE-FLOW project the implementation of different catalysts in "compartments" provided by Pickering emulsions and their application in continuous flow is targeted. We present here the development of heterogeneous Pd catalysts that are ready to be used in combination with biocatalysts for catalytic cascade synthesis of active pharmaceutical ingredients (APIs). In particular, we focus on the application of the catalytic systems for Suzuki-Miyaura cross-coupling reactions, which is the key step in the synthesis of the targeted APIs valsartan and sacubitril. An immobilised enzyme will accomplish the final product formation via hydrolysis. In order to create a large interfacial area for the catalytic reactions and to keep the reagents separated until required, the catalyst particles are used to stabilise Pickering emulsions of oil and water. A set of Ce-Sn-Pd oxides with the molecular formula Ce 0.99- x Sn x Pd 0.01 O 2-δ ( x = 0-0.99) has been prepared utilising a simple single-step solution combustion method. The high applicability of the catalysts for different functional groups and their minimal leaching behaviour is demonstrated with various Suzuki-Miyaura cross-coupling reactions in batch as well as in continuous flow employing the so-called "plug & play reactor". Finally, we demonstrate the use of these particles as the sole emulsifier of oil-water emulsions for a range of oils.

Synthesis, Structural Characterization and Antinociceptive Activities of New Arylated Quinolines via Suzuki-Miyaura Cross Coupling Reaction.

PubMed

Ullah, Malik A; Adeel, Muhammad; Tahir, Muhammad N; Rauf, Abdur; Akram, Muhammad; Hadda, Taibi B; Mabkhot, Yahia N; Muhammad, Naveed; Naseer, Fehmida; Mubarak, Mohammad S

2017-01-01

The quinoline ring system is one of the most commonly encountered heterocycles in medicinal chemistry, due to the pharmaceutical and medicinal uses of derivatives containing this ring. These quinoline-based compounds have remarkable biological activity, as they are employed as antimalarial, antibacterial, antifungal, and antitumor agents. The quinoline nucleus can be synthesized by various traditional methods such as the Skraup reaction, Friedlaender synthesis, Combes quinoline synthesis, Larock quinoline synthesis, among others. The aim of the present work is to synthesize a number of new arylated quninolines having significant antinoceciptive effect through the Suzuki-Miyaura cross coupling reaction using 3- bromoquinoline as a starting material. A number of new quinoline derivatives have been synthesized. Structures of the newly synthesized compounds were confirmed by means of IR, NMR, and mass spectrometry, and by elemental analysis. In addition, the molecular structures of two representative derivatives were determined with the aid of X-ray crystallography. Additionally, the antinociceptive activity of the prepared compounds was evaluated in vivo; results revealed that most of the tested compounds exhibited a dosedependent antinociceptive effect. Prepared compounds were found to exhibit significant antinociceptive activities and could be used as potential analgesic agents. Further work, however, may be required to establish the safety and efficacy of these compounds. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Catalytic Palladium Film Deposited by Scalable Low-Temperature Aqueous Combustion.

PubMed

Voskanyan, Albert A; Li, Chi-Ying Vanessa; Chan, Kwong-Yu

2017-09-27

This article describes a novel method for depositing a dense, high quality palladium thin film via a one-step aqueous combustion process which can be easily scaled up. Film deposition of Pd from aqueous solutions by conventional chemical or electrochemical methods is inhibited by hydrogen embrittlement, thus resulting in a brittle palladium film. The method outlined in this work allows a direct aqueous solution deposition of a mirror-bright, durable Pd film on substrates including glass and glassy carbon. This simple procedure has many advantages including a very high deposition rate (>10 cm 2 min -1 ) and a relatively low deposition temperature (250 °C), which makes it suitable for large-scale industrial applications. Although preparation of various high-quality oxide films has been successfully accomplished via solution combustion synthesis (SCS) before, this article presents the first report on direct SCS production of a metallic film. The mechanism of Pd film formation is discussed with the identification of a complex formed between palladium nitrate and glycine at low temperature. The catalytic properties and stability of films are successfully tested in alcohol electrooxidation and electrochemical oxygen reduction reaction. It was observed that combustion deposited Pd film on a glassy carbon electrode showed excellent catalytic activity in ethanol oxidation without using any binder or additive. We also report for the first time the concept of a reusable "catalytic flask" as illustrated by the Suzuki-Miyaura cross-coupling reaction. The Pd film uniformly covers the inner walls of the flask and eliminates the catalyst separation step. We believe the innovative concept of a reusable catalytic flask is very promising and has the required features to become a commercial product in the future.

Accessing conjugated polymers with precisely controlled heterobisfunctional chain ends via post-polymerization modification of the OTf group and controlled Pd(0)/t-Bu 3P-catalyzed Suzuki cross-coupling polymerization

DOE PAGES

Hu, Qiao -Sheng; Hong, Kunlun; Zhang, Hong -Hai

2015-08-12

In this study, a general strategy toward the synthesis of well-defined conjugated polymers with controlled heterobisfunctional chain ends via combination of controlled Pd(0)/t-Bu 3P Suzuki cross-coupling polymerization with the post-polymerization modification of the triflate (OTf) group was disclosed.

Accessing conjugated polymers with precisely controlled heterobisfunctional chain ends via post-polymerization modification of the OTf group and controlled Pd(0)/t-Bu 3P-catalyzed Suzuki cross-coupling polymerization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hu, Qiao -Sheng; Hong, Kunlun; Zhang, Hong -Hai

In this study, a general strategy toward the synthesis of well-defined conjugated polymers with controlled heterobisfunctional chain ends via combination of controlled Pd(0)/t-Bu 3P Suzuki cross-coupling polymerization with the post-polymerization modification of the triflate (OTf) group was disclosed.

Green synthesis, characterization and catalytic activity of the Pd/TiO2 nanoparticles for the ligand-free Suzuki-Miyaura coupling reaction.

PubMed

Nasrollahzadeh, Mahmoud; Sajadi, S Mohammad

2016-03-01

A green synthesis process was developed for production of the Pd/TiO2 nanoparticles (NPs) without using toxic, hazardous and dangerous materials. Myrtus communis L. leaf extract serves as a mild, renewable and non-toxic reducing agent. The advantages of this biosynthesis method include use of cheap, clean, nontoxic and environmentally benign precursors and simple procedures without time-consuming polymerization and problems with treatment of a highly viscous polymeric resin. More importantly, the synthesized Pd/TiO2 NPs presented excellent catalytic activity for ligand-free Suzuki-Miyaura coupling which could be easily separated from the reaction mixture and reused many times with no loss of activity. Therefore, these properties indicate demonstrative benefits of the catalyst. The Pd/TiO2 NPs was characterized by FESEM, TEM, FT-IR, UV-vis spectroscopy and EDS. Copyright © 2015 Elsevier Inc. All rights reserved.

Elucidation of the structure-property relationship of p-type organic semiconductors through rapid library construction via a one-pot, Suzuki-Miyaura coupling reaction.

PubMed

Fuse, Shinichiro; Matsumura, Keisuke; Wakamiya, Atsushi; Masui, Hisashi; Tanaka, Hiroshi; Yoshikawa, Susumu; Takahashi, Takashi

2014-09-08

The elucidation of the structure-property relationship is an important issue in the development of organic electronics. Combinatorial synthesis and the evaluation of systematically modified compounds is a powerful tool in the work of elucidating structure-property relationships. In this manuscript, D-π-A structure, 32 p-type organic semiconductors were rapidly synthesized via a one-pot, Suzuki-Miyaura coupling with subsequent Knoevenagel condensation. Evaluation of the solubility and photovoltaic properties of the prepared compounds revealed that the measured solubility was strongly correlated with the solubility parameter (SP), as reported by Fedors. In addition, the SPs were correlated with the Jsc of thin-film organic solar cells prepared using synthesized compounds. Among the evaluated photovoltaic properties of the solar cells, Jsc and Voc had strong correlations with the photoconversion efficiency (PCE).

Expeditious Preparation of Open-Cage Fullerenes by Rhodium(I)-Catalyzed [2+2+2] Cycloaddition of Diynes and C60: an Experimental and Theoretical Study.

PubMed

Artigas, Albert; Pla-Quintana, Anna; Lledó, Agustí; Roglans, Anna; Solà, Miquel

2018-06-04

A novel methodology to transform C60 into a variety of open-cage fullerene derivatives employing rhodium(I) catalysis has been developed. This transformation encompasses a partially intermolecular [2+2+2] cycloaddition reaction between diynes 1 and C60 to deliver a cyclohexadiene-fused fullerene, which concomitantly undergoes a formal [4+4]/retro-[2+2+2] rearrangement to deliver open-cage fullerenes 2. Most notably, this process occurs without the need of photoexcitation. The complete mechanism of this transformation has been rationalized by DFT calculations, which indicate that, after [2+2+2] cycloaddition, the cyclohexadiene-fused intermediate evolves into the final product through a Rh-catalyzed di-π-methane rearrangement followed by a retro-[2+2+2] cycloaddition. The obtained open-cage fullerenes can be derivatized by Suzuki-Miyaura cross-coupling, or subjected to ring expansion to deliver a 12-membered ring orifice in the fullerene structure. Overall, the methodology presented constitutes a straightforward entry to functional open-cage C60-fullerene derivatives employing catalytic methods. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Stereoselective synthesis of novel highly substituted isochromanone and isoquinolinone-containing exocyclic tetrasubstituted alkenes.

PubMed

Arthuis, Martin; Pontikis, Renée; Florent, Jean-Claude

2009-03-06

An efficient synthetic route toward the synthesis of highly substituted arylethylidene-isoquinolinones/isochromanones is reported. The tandem carbopalladation/Suzuki-Miyaura coupling sequence stereoselectively provided various functionalized polycyclic compounds in moderate to excellent yields.

Synthesis of 3-iodoindoles by the Pd/Cu-catalyzed coupling of N,N-dialkyl-2-iodoanilines and terminal acetylenes, followed by electrophilic cyclization.

PubMed

Yue, Dawei; Yao, Tuanli; Larock, Richard C

2006-01-06

[reaction: see text] 3-Iodoindoles have been prepared in excellent yields by coupling terminal acetylenes with N,N-dialkyl-o-iodoanilines in the presence of a Pd/Cu catalyst, followed by an electrophilic cyclization of the resulting N,N-dialkyl-o-(1-alkynyl)anilines using I2 in CH2Cl2. Aryl-, vinylic-, alkyl-, and silyl-substituted terminal acetylenes undergo this process to produce excellent yields of 3-iodoindoles. The reactivity of the carbon-nitrogen bond cleavage during cyclization follows the following order: Me > n-Bu, Me > Ph, and cyclohexyl > Me. Subsequent palladium-catalyzed Sonogashira, Suzuki, and Heck reactions of the resulting 3-iodoindoles proceed smoothly in good yields.

"Greening up" the Suzuki Reaction

ERIC Educational Resources Information Center

Aktoudianakis, Evangelos; Chan, Elton; Edward, Amanda R.; Jarosz, Isabel; Lee, Vicki; Mui, Leo; Thatipamala, Sonya S.; Dicks, Andrew P.

2008-01-01

This article describes the rapid, green synthesis of a biaryl compound (4-phenylphenol) via a Pd(0)-catalyzed Suzuki cross-coupling reaction in water. Mild reaction conditions and operational simplicity makes this experiment especially amenable to both mid- and upper-level undergraduates. The methodology exposes students to purely aqueous…

On the stereochemical course of palladium-catalyzed cross-coupling of allylic silanolate salts with aromatic bromides.

PubMed

Denmark, Scott E; Werner, Nathan S

2010-03-17

The stereochemical course of palladium-catalyzed cross-coupling reactions of an enantioenriched, alpha-substituted, allylic silanolate salt with aromatic bromides has been investigated. The allylic silanolate salt was prepared in high geometrical (Z/E, 94:6) and high enantiomeric (94:6 er) purity by a copper-catalyzed S(N)2' reaction of a resolved allylic carbamate. Eight different aromatic bromides underwent cross-coupling with excellent constitutional site-selectivity and excellent stereospecificity. Stereochemical correlation established that the transmetalation event proceeds through a syn S(E)' mechanism which is interpreted in terms of an intramolecular delivery of the arylpalladium electrophile through a key intermediate that contains a discrete Si-O-Pd linkage.

Preparation of metallic Pd nanoparticles using supercritical CO2 deposition: An efficient catalyst for Suzuki cross-coupling reaction

NASA Astrophysics Data System (ADS)

Tezcan, Burcu; Ulusal, Fatma; Egitmen, Asım; Guzel, Bilgehan

2018-05-01

Ligand-free palladium nanoparticles supported on multi-walled carbon nanotubes (Pd/MWCNT) were prepared by the supercritical carbon dioxide (scCO2) deposition method using a novel scCO2-soluble Pd organometallic complex as a precursor. The precursor with the perfluoroalkyl chain group was synthesized and identified by microanalytic methods. The deposition was carried out at the temperature of 363.15 K and pressure of 27.6 MPa CO2. The prepared metallic nanoparticles were obtained with an average size of 2 nm. Pd/MWCNT was utilized as a heterogeneous catalyst in Suzuki cross-coupling reaction. The nanocatalyst was found very effective in Suzuki reaction and it could also be recovered easily from the reaction media and reused over several cycles without significant loss of catalytic activity under mild conditions. [Figure not available: see fulltext.

Fluorescent nanoaggregates of pentacenequinone derivative for selective sensing of picric acid in aqueous media.

PubMed

Bhalla, Vandana; Gupta, Ankush; Kumar, Manoj

2012-06-15

Novel pentacenequinone derivative 3 has been synthesized using the Suzuki-Miyaura coupling protocol which forms fluorescent nanoaggregates in aqueous media due to its aggregation-induced emission enhancement attributes and selectively senses picric acid with a detection limit of 500 ppb.

Palladium-catalyzed C-H functionalization of acyldiazomethane and tandem cross-coupling reactions.

PubMed

Ye, Fei; Qu, Shuanglin; Zhou, Lei; Peng, Cheng; Wang, Chengpeng; Cheng, Jiajia; Hossain, Mohammad Lokman; Liu, Yizhou; Zhang, Yan; Wang, Zhi-Xiang; Wang, Jianbo

2015-04-08

Palladium-catalyzed C-H functionalization of acyldiazomethanes with aryl iodides has been developed. This reaction is featured by the retention of the diazo functionality in the transformation, thus constituting a novel method for the introduction of diazo functionality to organic molecules. Consistent with the experimental results, the density functional theory (DFT) calculation indicates that the formation of Pd-carbene species in the catalytic cycle through dinitrogen extrusion from the palladium ethyl diazoacetate (Pd-EDA) complex is less favorable. The reaction instead proceeds through Ag2CO3 assisted deprotonation and subsequently reductive elimination to afford the products with diazo functionality remained. This C-H functionalization transformation can be further combined with the recently evolved palladium-catalyzed cross-coupling reaction of diazo compounds with aryl iodides to develop a tandem coupling process for the synthesis of α,α-diaryl esters. DFT calculation supports the involvement of Pd-carbene as reactive intermediate in the catalytic cycle, which goes through facile carbene migratory insertion with a low energy barrier (3.8 kcal/mol).

Synthesis and biological evaluation of vinylogous combretastatin A-4 derivatives.

PubMed

Kaffy, Julia; Pontikis, Renée; Florent, Jean-Claude; Monneret, Claude

2005-07-21

Stereospecific syntheses of the Z-E and E-Z vinylogues of combretastatin A-4, and two B-ring related analogues, were achieved through a Suzuki-Miyaura coupling. As compared to CA4, the derivative with a phenyl moiety has shown increased potency in its ability to inhibit tubulin polymerisation.

NiXantphos: a deprotonatable ligand for room-temperature palladium-catalyzed cross-couplings of aryl chlorides.

PubMed

Zhang, Jiadi; Bellomo, Ana; Trongsiriwat, Nisalak; Jia, Tiezheng; Carroll, Patrick J; Dreher, Spencer D; Tudge, Matthew T; Yin, Haolin; Robinson, Jerome R; Schelter, Eric J; Walsh, Patrick J

2014-04-30

Although the past 15 years have witnessed the development of sterically bulky and electron-rich alkylphosphine ligands for palladium-catalyzed cross-couplings with aryl chlorides, examples of palladium catalysts based on either triarylphosphine or bidentate phosphine ligands for efficient room temperature cross-coupling reactions with unactivated aryl chlorides are rare. Herein we report a palladium catalyst based on NiXantphos, a deprotonatable chelating aryldiphosphine ligand, to oxidatively add unactivated aryl chlorides at room temperature. Surprisingly, comparison of an extensive array of ligands revealed that under the basic reaction conditions the resultant heterobimetallic Pd-NiXantphos catalyst system outperformed all the other mono- and bidentate ligands in a deprotonative cross-coupling process (DCCP) with aryl chlorides. The DCCP with aryl chlorides affords a variety of triarylmethane products, a class of compounds with various applications and interesting biological activity. Additionally, the DCCP exhibits remarkable chemoselectivity in the presence of aryl chloride substrates bearing heteroaryl groups and sensitive functional groups that are known to undergo 1,2-addition, aldol reaction, and O-, N-, enolate-α-, and C(sp(2))-H arylations. The advantages and importance of the Pd-NiXantphos catalyst system outlined herein make it a valuable contribution for applications in Pd-catalyzed arylation reactions with aryl chlorides.

NiXantphos: A Deprotonatable Ligand for Room-Temperature Palladium-Catalyzed Cross-Couplings of Aryl Chlorides

PubMed Central

2015-01-01

Although the past 15 years have witnessed the development of sterically bulky and electron-rich alkylphosphine ligands for palladium-catalyzed cross-couplings with aryl chlorides, examples of palladium catalysts based on either triarylphosphine or bidentate phosphine ligands for efficient room temperature cross-coupling reactions with unactivated aryl chlorides are rare. Herein we report a palladium catalyst based on NiXantphos, a deprotonatable chelating aryldiphosphine ligand, to oxidatively add unactivated aryl chlorides at room temperature. Surprisingly, comparison of an extensive array of ligands revealed that under the basic reaction conditions the resultant heterobimetallic Pd–NiXantphos catalyst system outperformed all the other mono- and bidentate ligands in a deprotonative cross-coupling process (DCCP) with aryl chlorides. The DCCP with aryl chlorides affords a variety of triarylmethane products, a class of compounds with various applications and interesting biological activity. Additionally, the DCCP exhibits remarkable chemoselectivity in the presence of aryl chloride substrates bearing heteroaryl groups and sensitive functional groups that are known to undergo 1,2-addition, aldol reaction, and O-, N-, enolate-α-, and C(sp2)–H arylations. The advantages and importance of the Pd–NiXantphos catalyst system outlined herein make it a valuable contribution for applications in Pd-catalyzed arylation reactions with aryl chlorides. PMID:24745758

Expedient construction of small molecule macroarrays via sequential palladium- and copper-mediated reactions and their ex situ biological testing.

PubMed

Frei, Reto; Breitbach, Anthony S; Blackwell, Helen E

2012-05-01

We report the highly efficient syntheses of a series of focused libraries in the small molecule macroarray format using Suzuki-Miyaura and copper-catalyzed azide-alkyne cycloaddition (or "click") reactions. The libraries were based on stilbene and triazole scaffolds, which are known to have a broad range of biological activities, including quorum-sensing (QS) modulation in bacteria. The library products were generated in parallel on the macroarray in extremely short reaction times (~10-20 min) and isolated in excellent purities. Biological testing of one macroarray library post-cleavage (ex situ) revealed several potent agonists of the QS receptor, LuxR, in Vibrio fischeri. These synthetic agonists, in contrast to others that we have reported, were only active in the presence of the native QS signal in V. fischeri, which is suggestive of a different mode of activity. Notably, the results presented herein showcase the ready compatibility of the macroarray platform with chemical reactions that are commonly utilized in small molecule probe and drug discovery today. As such, this work serves to expand the utility of the small molecule macroarray as a rapid and operationally straightforward approach toward the synthesis and screening of bioactive agents.

Size control and catalytic activity of bio-supported palladium nanoparticles.

PubMed

Søbjerg, Lina Sveidal; Lindhardt, Anders T; Skrydstrup, Troels; Finster, Kai; Meyer, Rikke Louise

2011-07-01

The development of nanoparticles has greatly improved the catalytic properties of metals due to the higher surface to volume ratio of smaller particles. The production of nanoparticles is most commonly based on abiotic processes, but in the search for alternative protocols, bacterial cells have been identified as excellent scaffolds of nanoparticle nucleation, and bacteria have been successfully employed to recover and regenerate platinum group metals from industrial waste. We report on the formation of bio-supported palladium (Pd) nanoparticles on the surface of two bacterial species with distinctly different surfaces: the gram positive Staphylococcus sciuri and the gram negative Cupriavidus necator. We investigated how the type of bacterium and the amount of biomass affected the size and catalytic properties of the nanoparticles formed. By increasing the biomass:Pd ratio, we could produce bio-supported Pd nanoparticles smaller than 10nm in diameter, whereas lower biomass:Pd ratios resulted in particles ranging from few to hundreds of nm. The bio-supported Pd nanoparticle catalytic properties were investigated towards the Suzuki-Miyaura cross coupling reaction and hydrogenation reactions. Surprisingly, the smallest nanoparticles obtained at the highest biomass:Pd ratio showed no reactivity towards the test reactions. The lack of reactivity appears to be caused by thiol groups, which poison the catalyst by binding strongly to Pd. Different treatments intended to liberate particles from the biomass, such as burning or rinsing in acetone, did not re-establish their catalytic activity. Sulphur-free biomaterials should therefore be explored as more suitable scaffolds for Pd(0) nanoparticle formation. Copyright © 2011 Elsevier B.V. All rights reserved.

Palladium- and nickel-catalyzed Kumada cross-coupling reactions of gem-difluoroalkenes and monofluoroalkenes with Grignard reagents.

PubMed

Dai, Wenpeng; Xiao, Juan; Jin, Guanyi; Wu, Jingjing; Cao, Song

2014-11-07

A novel Kumada-Tamao-Corriu cross-coupling reaction of gem-di- or monofluoroalkenes with Grignard reagents, with or without β-hydrogen atoms, in the presence of a catalytic amount of palladium- or nickel-based catalysts has been developed. The reaction is performed under mild conditions (room temperature or reflux in diethyl ether for 1-2 h) and leads to di-cross- or mono-cross-coupled products in good to high yields.

Palladium-Catalyzed, Copper(I)-Mediated Coupling of Boronic Acids and Benzylthiocyanate. A Cyanide-Free Cyanation of Boronic Acids

PubMed Central

Zhang, Zhihui; Liebeskind, Lanny S.

2008-01-01

A new method for the synthesis of nitriles is described. As a complement to the classic cyanation of aryl halides using cyanide sources and a transition metal catalyst, the palladium-catalyzed cross-coupling of thiocyanates with boronic acids in the presence of copper(I) thiophene-2-carboxylate (CuTC) affords nitriles in good to excellent yields. PMID:16956219

Synthesis of 24-phenyl-24-oxo steroids derived from bile acids by palladium-catalyzed cross coupling with phenylboronic acid. NMR characterization and X-ray structures.

PubMed

Mayorquín-Torres, Martha C; Romero-Ávila, Margarita; Flores-Álamo, Marcos; Iglesias-Arteaga, Martin A

2013-11-01

Palladium-catalyzed cross coupling of phenyboronic acid with acetylated bile acids in which the carboxyl functions have been activated by formation of a mixed anhydride with pivalic anhydride afforded moderate to good yield of 24-phenyl-24-oxo-steroids. Unambiguous assignments of the NMR signals were made with the aid of combined 1D and 2D NMR techniques. X-ray diffraction studies confirmed the obtained structures. Copyright © 2013 Elsevier Inc. All rights reserved.

Palladium-catalyzed cross-coupling of aryl chlorides and triflates with sodium cyanate: A practical synthesis of unsymmetrical ureas

PubMed Central

Vinogradova, Ekaterina V.; Fors, Brett P.; Buchwald, Stephen L.

2012-01-01

An efficient method for palladium-catalyzed cross-coupling of aryl chlorides and triflates with sodium cyanate is reported. The protocol allows for the synthesis of unsymmetrical N,N'-di- and N,N,N'-trisubstituted ureas in one pot, and is tolerant of a wide range of functional groups. Insight into the mechanism of aryl isocyanate formation is gleaned through studies of the transmetallation and reductive elimination steps of the reaction, including the first demonstration of reductive elimination from an arylpalladium isocyanate complex to produce an aryl isocyanate. PMID:22716197

Microwave-Assisted Synthesis of 5-Phenyl-2-Hydroxyacetophenone Derivatives by a Green Suzuki Coupling Reaction

ERIC Educational Resources Information Center

Soares, Pedro; Fernandes, Carlos; Chavarria, Daniel; Borges, Fernanda

2015-01-01

In recent years, the use of boron-containing reagents in palladium-assisted C-C coupling reactions (the Suzuki reaction) has gained prominence due to the vast array of reagents commercially available. Consequently, the generation of carbon-carbon bonds, namely of functionalized biphenyl systems, is at present considered the backbone of organic…

A new chitosan Schiff base supported Pd(II) complex for microwave-assisted synthesis of biaryls compounds

NASA Astrophysics Data System (ADS)

Baran, Talat

2017-08-01

In this study, a new heterogeneous palladium (II) catalyst that contains O-carboxymethyl chitosan Schiff base has been designed for Suzuki coupling reactions. The chemical structures of the synthesized catalyst were characterized with the FTIR, TG/DTG, ICP-OES, SEM/EDAX, 1H NMR, 13C NMR, GC/MS, XRD, and magnetic moment techniques. The reusability and catalytic behavior of heterogeneous catalyst was tested towards Suzuki reactions. As a result of the tests, excellent selectivity was obtained, and by-products of homo coupling were not seen in the spectra. The biaryls products were identified on a GC/MS. In addition, it was determined in the reusability tests that the catalysts could be used several times (seven runs). More importantly, with very low catalyst loading (6 × 10-3 mol %) in very short reaction time (5 min), chitosan Schiff base supported Pd(II) complex gave high TON and TOF values. These findings showed that Schiff base supported Pd(II) catalyst is suitable for Suzuki cross coupling reactions.

NCN-Coordinating Ligands based on Pyrene Structure with Potential Application in Organic Electronics.

PubMed

Zych, Dawid; Kurpanik, Aneta; Slodek, Aneta; Maroń, Anna; Pająk, Michał; Szafraniec-Gorol, Grażyna; Matussek, Marek; Krompiec, Stanisław; Schab-Balcerzak, Ewa; Kotowicz, Sonia; Siwy, Mariola; Smolarek, Karolina; Maćkowski, Sebastian; Danikiewicz, Witold

2017-11-07

Five novel derivatives of pyrene, substituted at positions 1,3,6,8 with 4-(2,2-dimethylpropyloxy)pyridine (P1), 4-decyloxypyridine (P2), 4-pentylpyridine (P3), 1-decyl-1,2,3-triazole (P4), and 1-benzyl-1,2,3-triazole (P5), are obtained through a Suzuki-Miyaura cross-coupling reaction or Cu I -catalyzed 1,3-dipolar cycloaddition reaction, respectively, and characterized thoroughly. TGA measurements reveal the high thermal stability of the compounds. Pyrene derivatives P1-P5 all show photoluminescence (PL) quantum yields (Φ) of approximately 75 % in solution. Solid-state photo- and electroluminescence characteristics of selected compounds as organic light-emitting diodes are tested. In the guest-host configuration, two matrixes, that is, poly(N-vinylcarbazole) (PVK) and a binary matrix consisting of PVK and 2-tert-butylphenyl-5-biphenyl-1,3,4-oxadiazole (PBD) (50:50 wt %), are applied. The diodes show red, green, or blue electroluminescence, depending on both the compound chemical structure and the actual device architecture. In addition, theoretical studies (DFT and TD-DFT) provide a deeper understanding of the experimental results. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Comparison of the catalytic activity for the Suzuki-Miyaura reaction of (η(5)-Cp)Pd(IPr)Cl with (η(3)-cinnamyl)Pd(IPr)(Cl) and (η(3)-1-t-Bu-indenyl)Pd(IPr)(Cl).

PubMed

Melvin, Patrick R; Hazari, Nilay; Lant, Hannah M C; Peczak, Ian L; Shah, Hemali P

2015-01-01

Complexes of the type (η(3)-allyl)Pd(L)(Cl) and (η(3)-indenyl)Pd(L)(Cl) are highly active precatalysts for the Suzuki-Miyaura reaction. Even though allyl and indenyl ligands are similar to cyclopentadienyl (Cp) ligands, there have been no detailed comparative studies exploring the activity of precatalysts of the type (η(5)-Cp)Pd(L)(Cl) for Suzuki-Miyaura reactions. Here, we compare the catalytic activity of (η(5)-Cp)Pd(IPr)(Cl) (IPr = 1,3-bis(2,6-diisopropylphenyl)-1,3-dihydro-2H-imidazol-2-ylidene, Cp) with two commercially available catalysts (η(3)-cinnamyl)Pd(IPr)(Cl) (Cin) and (η(3)-1-t-Bu-indenyl)Pd(IPr)(Cl) ( (tBu) Ind). We show that Cp gives slightly better catalytic activity than Cin, but significantly inferior activity than (tBu) Ind. This order of activity is rationalized by comparing the rates at which the precatalysts are activated to the monoligated Pd(0) active species along with the tendency of the starting precatalysts to comproportionate with monoligated Pd(0) to form inactive Pd(I) dimers. As part of this work the Cp supported Pd(I) dimer (μ-Cp)(μ-Cl)Pd2(IPr)2 (Cp (Dim) ) was synthesized and crystallographically characterized. It does not readily disproportionate to form monoligated Pd(0) and consequently Cp (Dim) is a poor catalyst for the Suzuki-Miyaura reaction.

General Synthesis of Alkenyl Sulfides by Palladium-Catalyzed Thioetherification of Alkenyl Halides and Tosylates.

PubMed

Velasco, Noelia; Virumbrales, Cintia; Sanz, Roberto; Suárez-Pantiga, Samuel; Fernández-Rodríguez, Manuel A

2018-05-08

The cross-coupling reaction of alkenyl bromides with thiols catalyzed by palladium complexes derived from inexpensive dppf ligand is reported. These reactions occur under low catalyst loading and in high yields and display wide scope, including the coupling of bulky thiols and trisubstituted bromoolefins, and functional group tolerance. In addition, the thioetherification of less reactive chloroalkenes and, for the first time, alkenyl tosylates was accomplished using a catalyst generated from CyPF tBu alkylbisphosphine ligand.

Palladium-catalyzed Heck-type cross-couplings of unactivated alkyl iodides.

PubMed

McMahon, Caitlin M; Alexanian, Erik J

2014-06-02

A palladium-catalyzed, intermolecular Heck-type coupling of alkyl iodides and alkenes is described. This process is successful with a variety of primary and secondary unactivated alkyl iodides as reaction partners, including those with hydrogen atoms in the β position. The mild catalytic conditions enable intermolecular C-C bond formations with a diverse set of alkyl iodides and alkenes, including substrates containing base- or nucleophile-sensitive functionality. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A Colorimetric Chemodosimeter for Pd(II): A Method for Detecting Residual Palladium in Cross-Coupling Reactions

PubMed Central

Houk, Ronald J. T.; Wallace, Karl J.; Hewage, Himali S.; Anslyn, Eric V.

2008-01-01

A colorimetric chemodosimeter (SQ1) for the detection of trace palladium salts in cross-coupling reactions mediated by palladium is described. Decolorization of SQ1 is affected by nucleophilic attack of ethanethiol in basic DMSO solutions. Thiol addition is determined to have an equilibrium constant (Keq) of 2.9 × 106 M-1, with a large entropic and modest enthalpic driving force. This unusual result is attributed to solvent effects arising from a strong coordinative interaction between DMSO and the parent squaraine. Palladium detection is achieved through thiol scavenging from the SQ1-ethanethiol complex leading to a color “turn-on” of the parent squaraine. It was found that untreated samples obtained directly from Suzuki couplings showed no response to the assay. However, treatment of the samples with aqueous nitric acid generates a uniform Pd(NO3)2 species, which gives an appropriate response. “Naked-eye” detection of Pd(NO3)2 was estimated to be as low as 0.5 ppm in solution, and instrument-based detection was tested as low as 100 ppb. The average error over the working range of the assay was determined to be 7%. PMID:19122841

Synthesis of Rhodamines from Fluoresceins Using Pd-Catalyzed C–N Cross-Coupling

PubMed Central

2011-01-01

A unified, convenient, and efficient strategy for the preparation of rhodamines and N,N′-diacylated rhodamines has been developed. Fluorescein ditriflates were found to undergo palladium-catalyzed C–N cross-coupling with amines, amides, carbamates, and other nitrogen nucleophiles to provide direct access to known and novel rhodamine derivatives, including fluorescent dyes, quenchers, and latent fluorophores. PMID:22091952

Biaryl Phosphine Ligands in Palladium-Catalyzed Amination

PubMed Central

Surry, David S.

2012-01-01

Palladium-catalyzed amination of aryl halides has undergone rapid development in the last 12 years. This has been largely driven by implementation of new classes of ligands. Biaryl phosphines have proven to provide especially active catalysts in this context. This review discusses the applications that these catalysts have found in C-N cross-coupling in heterocycle synthesis, pharmaceuticals, materials science and natural product synthesis. PMID:18663711

Synthesis of Thieno[3,2-b]indoles via Halogen Dance and Ligand-Controlled One-Pot Sequential Coupling Reaction.

PubMed

Hayashi, Yuki; Okano, Kentaro; Mori, Atsunori

2018-02-16

A two-pot synthesis of thieno[3,2-b]indole from 2,5-dibromothiophene is described. A halogen dance of 2,5-dibromothiophene was performed with LDA, and subsequent Negishi coupling was performed with 2-iodoaniline derivatives to provide the corresponding coupling products. The resulting two bromo groups have different reactivities, which were utilized for the one-pot Suzuki-Miyaura coupling/intramolecular Buchwald-Hartwig amination to produce thieno[3,2-b]indole via an assisted tandem catalysis that involved in situ ligand exchange.

BCl3 -Induced Annulative Oxo- and Thioboration for the Formation of C3-Borylated Benzofurans and Benzothiophenes.

PubMed

Warner, Andrew J; Churn, Anna; McGough, John S; Ingleson, Michael J

2017-01-02

BCl 3 -induced borylative cyclization of aryl-alkynes possessing ortho-EMe (E=S, O) groups represents a simple, metal-free method for the formation of C3-borylated benzothiophenes and benzofurans. The dichloro(heteroaryl)borane primary products can be protected to form synthetically ubiquitous pinacol boronate esters or used in situ in Suzuki-Miyaura cross couplings to generate 2,3-disubstituted heteroarenes from simple alkyne precursors in one pot. In a number of cases alkyne trans-haloboration occurs alongside, or instead of, borylative cyclization and the factors controlling the reaction outcome are determined. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Synthesis of pyridine-fused perylene imides with an amidine moiety for hydrogen bonding.

PubMed

Ito, Satoru; Hiroto, Satoru; Shinokubo, Hiroshi

2013-06-21

Pyridine-fused perylene tetracarboxylic acid bisimides (PBIs) were synthesized via Suzuki-Miyaura coupling and acid condensation. The fused PBIs with electron-donating substituents exhibited an intramolecular charge transfer interaction. One of the N-alkyl substituents was selectively removed with BBr3 to create an amidine guest binding site. A hydrogen bonding interaction with pentafluorobenzoic acid changed the absorption spectra and enhanced fluorescence.

Enantiospecific sp2-sp3 coupling of secondary and tertiary boronic esters

NASA Astrophysics Data System (ADS)

Bonet, Amadeu; Odachowski, Marcin; Leonori, Daniele; Essafi, Stephanie; Aggarwal, Varinder K.

2014-07-01

The cross-coupling of boronic acids and related derivatives with sp2 electrophiles (the Suzuki-Miyaura reaction) is one of the most powerful C-C bond formation reactions in synthesis, with applications that span pharmaceuticals, agrochemicals and high-tech materials. Despite the breadth of its utility, the scope of this Nobel prize-winning reaction is rather limited when applied to aliphatic boronic esters. Primary organoboron reagents work well, but secondary and tertiary boronic esters do not (apart from a few specific and isolated examples). Through an alternative strategy, which does not involve using transition metals, we have discovered that enantioenriched secondary and tertiary boronic esters can be coupled to electron-rich aromatics with essentially complete enantiospecificity. As the enantioenriched boronic esters are easily accessible, this reaction should find considerable application, particularly in the pharmaceutical industry where there is growing awareness of the importance of, and greater clinical success in, creating biomolecules with three-dimensional architectures.

Applications of Palladium-Catalyzed C-N Cross-Coupling Reactions.

PubMed

Ruiz-Castillo, Paula; Buchwald, Stephen L

2016-10-12

Pd-catalyzed cross-coupling reactions that form C-N bonds have become useful methods to synthesize anilines and aniline derivatives, an important class of compounds throughout chemical research. A key factor in the widespread adoption of these methods has been the continued development of reliable and versatile catalysts that function under operationally simple, user-friendly conditions. This review provides an overview of Pd-catalyzed N-arylation reactions found in both basic and applied chemical research from 2008 to the present. Selected examples of C-N cross-coupling reactions between nine classes of nitrogen-based coupling partners and (pseudo)aryl halides are described for the synthesis of heterocycles, medicinally relevant compounds, natural products, organic materials, and catalysts.

Applications of Palladium-Catalyzed C–N Cross-Coupling Reactions

PubMed Central

2016-01-01

Pd-catalyzed cross-coupling reactions that form C–N bonds have become useful methods to synthesize anilines and aniline derivatives, an important class of compounds throughout chemical research. A key factor in the widespread adoption of these methods has been the continued development of reliable and versatile catalysts that function under operationally simple, user-friendly conditions. This review provides an overview of Pd-catalyzed N-arylation reactions found in both basic and applied chemical research from 2008 to the present. Selected examples of C–N cross-coupling reactions between nine classes of nitrogen-based coupling partners and (pseudo)aryl halides are described for the synthesis of heterocycles, medicinally relevant compounds, natural products, organic materials, and catalysts. PMID:27689804

GREENER SYNTHESIS OF ALIGNED PALLADIUM NANOBELTS AND NANOPLATES IN AQUEOUS MEDIUM USING VITAMIN B1

EPA Science Inventory

Palladium (Pd) plays an important role in many industrial and technological applications such as reduction of automobile pollutants, and Suzuki, Heck, and Stille coupling reactions. Consequently, a great deal of effort has been devoted to the synthesis of Pd nanostructures. Her...

Solid-phase organic synthesis of difluoroalkyl entities using a novel fluorinating cleavage strategy: part 1. Linker development: scope and limitations.

PubMed

Wiehn, Matthias S; Lindell, Stephen D; Bräse, Stefan

2009-01-01

An efficient method to synthesize gem-difluorinated compounds on solid supports is described. The strategy is based on the design of a novel sulfur linker system that enables, to the best of our knowledge for the first time, the release of target structures from the resin under simultaneous fluorination. Starting from an immobilized dithiol, coupling with an excess of aldehyde or ketone furnished dithianes. These can be further functionalized prior to release from the resin using our newly developed fluorinating cleavage conditions. Amide forming reactions, palladium-catalyzed reactions (Heck, Suzuki, and Sonogashira couplings), reductions, alkylations, and olefinations were successfully explored on the linker. The difluorinated target substances were obtained in modest to excellent yields and in high purities.

Palladium-catalyzed Kumada coupling reaction of bromoporphyrins with silylmethyl Grignard reagents: preparation of silylmethyl-substituted porphyrins as a multipurpose synthon for fabrication of porphyrin systems.

PubMed

Sugita, Noriaki; Hayashi, Satoshi; Hino, Fumio; Takanami, Toshikatsu

2012-12-07

We have developed an efficient method for preparing silylmethyl-substituted porphyrins via the palladium-catalyzed Kumada cross-coupling reaction of bromoporphyrins with silylmethyl Grignard reagents. We demonstrated the synthetic utility of these silylmethylporphyrins as a multipurpose synthon for fabricating porphyrin derivatives through a variety of transformations of the silylmethyl groups, including the DDQ-promoted oxidative conversion to CHO, CH(2)OH, CH(2)OMe, and CH(2)F functionalities and the fluoride ion-mediated desilylative introduction of carbon-carbon single and double bonds.

Controlled Pd(0)/t Bu3P Catalyzed Suzuki Cross-Coupling Polymerization of AB-Type Monomers with ArPd(t Bu3P)X or Pd2(dba)3/t Bu3P/ArX as the Initiator

DOE PAGES

Zhang, Honghai; Xing, Chun-Hui; Hu, Qiao-Sheng; ...

2015-02-05

The synthesis of well-defined and functionalized conjugated polymers, which are essential in the development of efficient organic electronics, through Suzuki cross-coupling polymerizations has been a challenging task. We developed controlled Pd(0)/t-Bu3P-catalyzed Suzuki cross-coupling polymerizations of AB-type monomers via the chain-growth mechanism with a series of in situ generated ArPd(t-Bu3P)X (X = I, Br, Cl) complexes as initiators. Among them, the combinations of Pd2(dba)3/t-Bu3P/p-BrC6H4I, Pd2(dba)3/t-Bu3P/p-BrC6H4CH2OH and Pd2(dba)3/t-Bu3P/p-PhCOC6H4Br were identified as highly robust initiator systems, resulting in polymers with predictable molecular weight and narrow polydispersity (PDI~1.13-1.20). In addition, Pd2(dba)3/t-Bu3P/p-BrC6H4CH2OH and Pd2(dba)3/t-Bu3P/p-PhCOC6H4Br initiator systems afforded functional polymers with >95% fidelity. Our results pavedmore » the road to access well-defined conjugated polymers, including conjugated polymers with complex polymer architectures such as block copolymers and branch copolymers.« less

Synthesis of enyne and aryl vinyl sulfoxides: functionalization via Pummerer rearrangement.

PubMed

Souza, Frederico B; Shamim, Anwar; Argomedo, Luiz M Z; Pimenta, Daniel C; Stefani, Hélio A

2015-11-01

An efficient methodology for the synthesis of aryl-substituted vinyl sulfoxides through direct substitution of aryl-substituted alkynyl grignard reagents on menthyl-p-toluenesulfinate followed by Suzuki-Miyaura cross-coupling reaction has been developed. It has also been described that the reaction of alkyl-substituted and cycloalkyl-substituted alkynyl grignard reagents with menthyl-p-toluenesulfinate led to two products, i.e., alkynyl sulfoxide derivatives, as a result of substitution, and enyne sulfoxide derivatives, which resulted from substitution followed by Michael type addition. It was possible to selectively synthesize the enyne sulfoxide derivatives by changing the concentration of the grignard reagent. These alkenyl sulfoxides were transformed into the corresponding [Formula: see text]-thio aldehydes in high yields via additive Pummerer rearrangement.

Enantioselective gamma- and delta-Borylation of Unsaturated Carbonyl Derivatives: Synthesis, Mechanistic Insights, and Applications

NASA Astrophysics Data System (ADS)

Hoang, Gia L.

Chiral boronic esters are valuable synthetic intermediates widely used in a variety of stereospecific transformations. Transition metal-catalyzed asymmetric hydroboration (CAHB) of alkenes is among the most popular methods for their preparation. Enantioselective hydroboration of activated alkenes (i.e., vinyl arene derivatives or conjugated carbonyl compounds) have been extensively studied by many research groups. We, on the other hand, are interested in enantioselective hydroboration of unactivated alkenes utilizing coordinating functional groups (e.g., carbonyl derivatives) to give functionalized, chiral boronic esters. While conjugate addition and C-H activation methodologies provide efficient alternatives to CAHB for enantioselective beta-borylation of carbonyl compounds, direct gamma- and delta-borylations were essentially unknown prior to our wok on CAHB. The gamma-borylated products were used for understanding stereochemical aspects of Suzuki-Miyaura cross-coupling reactions resulting in stereoretention and in contrast to similar beta-borylated carbonyl derivatives reported in literature. Some other selected transformations were carried out to construct a number of biologically relevant structural motifs, such as lignan precursors, 1,4-amino alcohols, gamma-amino acid derivatives, 5-substitued-gamma-lactone and lactam ring systems. In addition, collaborative experimental and computational studies of the enantioselective desymmetrization via CAHB gain a better understanding of the mechanistic pathways.

Practical, economical, and eco-friendly starch-supported palladium catalyst for Suzuki coupling reactions.

PubMed

Baran, Talat

2017-06-15

In catalytic systems, the support materials need to be both eco friendly and low cost as well as having high thermal and chemical stability. In this paper, a novel starch supported palladium catalyst, which had these outstanding properties, was designed and its catalytic activity was evaluated in a Suzuki coupling reaction under microwave heating with solvent-free and mild reaction conditions. The starch supported catalyst gave remarkable reaction yields after only 5min as a result of the coupling reaction of the phenyl boronic acid with 23 different substrates, which are bearing aril bromide, iodide, and chloride. The longevity of the catalyst was also investigated, and the catalyst could be reused for 10 runs. The starch supported Pd(II) catalyst yielded remarkable TON (up to 25,000) and TOF (up to 312,500) values by using a simple, fast and eco-friendly method. In addition, the catalytic performance of the catalyst was tested against different commercial palladium catalysts, and the green starch supported catalyst had excellent selectivity. The catalytic tests showed that the novel starch based palladium catalyst proved to be an economical and practical catalyst for the synthesis of biaryl compounds. Copyright © 2017 Elsevier Inc. All rights reserved.

Magnetic Pd nanocatalyst Fe3O4@Pd for C-C bond formation and hydrogenation reactions

NASA Astrophysics Data System (ADS)

Biglione, Catalina; Cappelletti, Ariel L.; Strumia, Miriam C.; Martín, Sandra E.; Uberman, Paula M.

2018-05-01

Small core-shell Fe3O4@Pd superparamagnetic nanoparticles (MNPs) were obtained with good control in size and shape distribution by metal-complex thermal decomposition in organic media. The role of the stabilizer in the synthesis of MNPs was studied, employing oleylamine (OA), triphenylphosphine (TPP) and triphenylamine (TPA). The results revealed that, among the stabilizer investigated, the presence of oleylamine in the reaction media is crucial in order to obtain an uniform shell of Pd(0) in Fe3O4@Pd MNPs of 7 ± 1 nm. The synthesized core-shell MNPs were tested in Pd-catalyzed Heck-Mizoroki and Suzuki-Miyaura coupling reactions and p-chloronitrobenzene hydrogenation. High conversion, good reaction yields, and good TOF values were achieved in the three reaction systems with this nanocatalyst. The core-shell nanoparticle was easily recovered by a simple magnetic separation using a neodymium commercial magnet, which allowed performing up to four cycles of reuse. [Figure not available: see fulltext.

A General, Efficient and Functional-Group-Tolerant Catalyst System for the Palladium-Catalyzed Thioetherification of Aryl Bromides and Iodides

PubMed Central

Fernández-Rodríguez, Manuel A.; Hartwig, John F.

2010-01-01

The cross-coupling reaction of aryl bromides and iodides with aliphatic and aromatic thiols catalyzed by palladium complexes of the bisphosphine ligand CyPF-tBu (1) is reported. Reactions occur in excellent yields, broad scope, high tolerance of functional groups and with turnover numbers that exceed those of previous catalysts by two or three orders of magnitude. These couplings of bromo- and iodoarenes are more efficient than the corresponding reactions of chloroarenes and could be conducted with less catalyst loading and/or milder reaction conditions. Consequently, limitations regarding scope and functional group tolerance previously reported in the coupling of aryl chlorides are now overcome. PMID:19154131

Camphyl-based α-diimine palladium complexes: highly efficient precatalysts for direct arylation of thiazoles in open-air.

PubMed

Chen, Fu-Min; Lu, Dong-Dong; Hu, Li-Qun; Huang, Ju; Liu, Feng-Shou

2017-07-21

Based on the strategy of the development of phosphine-free palladium-catalyzed direct C-H arylation, a series of camphyl-based α-diimine palladium complexes bearing sterically bulky substituents were synthesized and characterized. The palladium complexes were applied for the cross-coupling of thiazole derivatives with aryl bromides. The effect of the sterically bulky substituent on the N-aryl moiety as well as the reaction conditions was screened. Under the optimal protocols, a wide range of aryl bromides can be smoothly coupled with thiazoles in good to excellent yields in the presence of a low palladium loading of 0.2 mol% under open-air conditions.

Synthesis of 1-methyleneindenes via palladium-catalyzed tandem reactions.

PubMed

Ye, Shengqing; Gao, Ke; Zhou, Haibo; Yang, Xiaodi; Wu, Jie

2009-09-28

Palladium-catalyzed tandem reactions of 2-alkenylphenyl-acetylenes with CuCl2 or CuBr2 afforded 3-chloro- or 3-bromo-1-methyleneindenes in good yields; these compounds could be further elaborated via palladium-catalyzed coupling reactions.

Design and Synthesis of Biaryl DNA-Encoded Libraries.

PubMed

Ding, Yun; Franklin, G Joseph; DeLorey, Jennifer L; Centrella, Paolo A; Mataruse, Sibongile; Clark, Matthew A; Skinner, Steven R; Belyanskaya, Svetlana

2016-10-10

DNA-encoded library technology (ELT) is a powerful tool for the discovery of new small-molecule ligands to various protein targets. Here we report the design and synthesis of biaryl DNA-encoded libraries based on the scaffold of 5-formyl 3-iodobenzoic acid. Three reactions on DNA template, acylation, Suzuki-Miyaura coupling and reductive amination, were applied in the library synthesis. The three cycle library of 3.5 million diversity has delivered potent hits for phosphoinositide 3-kinase α (PI3Kα).

Bite angle effects of diphosphines in C-C and C-X bond forming cross coupling reactions.

PubMed

Birkholz, Mandy-Nicole; Freixa, Zoraida; van Leeuwen, Piet W N M

2009-04-01

Catalytic reactions of C-C and C-X bond formation are discussed in this critical review with particular emphasis on cross coupling reactions catalyzed by palladium and wide bite angle bidentate diphosphine ligands. Especially those studies have been collected that allow comparison of the ligand bite angles for the selected ligands: dppp, BINAP, dppf, DPEphos and Xantphos. Similarities with hydrocyanation and CO/ethene/MeOH reactions have been highlighted, while rhodium hydroformylation has been mentioned as a contrasting example, in which predictability is high and steric and electronic effects follow smooth trends. In palladium catalysis wide bite angles and bulkiness of the ligands facilitate generally the reductive elimination thus giving more efficient cross coupling catalysis (174 references).

Weakly nucleophilic potassium aryltrifluoroborates in palladium-catalyzed Suzuki–Miyaura reactions: relative reactivity of K[4-RC6F4BF3] and the role of silver-assistance in acceleration of transmetallation

PubMed Central

Bardin, Vadim V; Shabalin, Anton Yu

2015-01-01

Summary Small differences in the reactivity of weakly nucleophilic potassium aryltrifluoroborates are revealed in the silver-assisted Pd-catalyzed cross-coupling of K[4-RC6F4BF3] (R = H, Bu, MeO, EtO, PrO, iPrO, BuO, t-BuO, CH2=CHCH2O, PhCH2O, PhCH2CH2O, PhO, F, pyrazol-1-yl, pyrrol-1-yl, and indol-1-yl) with ArX (4-BrC6H4CH3, 4-IC6H4F and 3-IC6H4F). An assumed role of silver(I) compounds AgmY (Y = O, NO3, SO4, BF4, F) consists in polarization of the Pd–X bond in neutral complex ArPdLnX with the generation of the related transition state or formation of [ArPdLn][XAgmY] with a highly electrophilic cation and subsequent transmetallation with the weakly nucleophilic borate. Efficiency of AgmY as a polarizing agent decreases in order Ag2O > AgNO3 ≈ Ag2SO4 > Ag[BF4] > AgF. No clear correlation between the reactivity of K[4-RC6F4BF3] and substituent electron parameters, σI and σR°, of the aryl group 4-RC6F4 was found. PMID:26124862

Design, Synthesis, and Validation of an Effective, Reusable Silicon-Based Transfer Agent for Room-Temperature Pd-Catalyzed Cross-Coupling Reactions of Aryl and Heteroaryl Chlorides with Readily Available Aryl Lithium Reagents

PubMed Central

Martinez-Solorio, Dionicio; Melillo, Bruno; Sanchez, Luis; Liang, Yong; Lam, Erwin; Houk, K. N.; Smith, Amos B.

2016-01-01

A reusable silicon-based transfer agent (1) has been designed, synthesized, and validated for effective room-temperature palladium-catalyzed cross-coupling reactions (CCRs) of aryl and heteroaryl chlorides with readily accessible aryl lithium reagents. The crystalline, bench-stable siloxane transfer agent (1) is easily prepared via a one-step protocol. Importantly, this “green” CCR protocol circumvents prefunctionalization, isolation of organometallic cross-coupling partners, and/or stoichiometric waste aside from LiCl. DFT calculations support a σ-bond metathesis mechanism during transmetalation and lead to insights on the importance of the CF3 groups. PMID:26835838

Decarbonylative Phosphorylation of Amides by Palladium and Nickel Catalysis: The Hirao Cross-Coupling of Amide Derivatives.

PubMed

Liu, Chengwei; Szostak, Michal

2017-10-02

Considering the ubiquity of organophosphorus compounds in organic synthesis, pharmaceutical discovery agrochemical crop protection and materials chemistry, new methods for their construction hold particular significance. A conventional method for the synthesis of C-P bonds involves cross-coupling of aryl halides and dialkyl phosphites (the Hirao reaction). We report a catalytic deamidative phosphorylation of a wide range of amides using a palladium or nickel catalyst giving aryl phosphonates in good to excellent yields. The present method tolerates a wide range of functional groups. The reaction constitutes the first example of a transition-metal-catalyzed generation of C-P bonds from amides. This redox-neutral protocol can be combined with site-selective conventional cross-coupling for the regioselective synthesis of potential pharmacophores. Mechanistic studies suggest an oxidative addition/transmetallation pathway. In light of the importance of amides and phosphonates as synthetic intermediates, we envision that this Pd and Ni-catalyzed C-P bond forming method will find broad application. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Applications of Iridium-Catalyzed Asymmetric Allylic Substitution Reactions in Target-Oriented Synthesis.

PubMed

Qu, Jianping; Helmchen, Günter

2017-10-17

Metal catalyzed allylic substitution is a cornerstone of organometallic and synthetic chemistry. Enantioselective versions have been developed with catalysts derived from transition metals, most notably molybdenum, nickel, ruthenium, rhodium, iridium, palladium, and copper. The palladium- and the iridium-catalyzed versions have turned out to be particularly versatile in organic synthesis because of the very broad scope of the nucleophile and great functional group compatibility. Assets of the iridium-catalyzed reaction are the formation of branched, chiral products from simple monosubstituted allylic substrates, high degrees of regio- and enantioselectivity, and use of modular, readily available chiral ligands. The possibility to use carbon, nitrogen, oxygen, and sulfur compounds as well as fluoride as nucleophiles allows a wide range of chiral building blocks to be prepared. Our Account begins with the presentation of fundamental reaction schemes and chiral ligands. We will focus our discussion on reactions promoted by phosphoramidite ligands, though numerous chiral ligands have been employed. The subsequent section presents a brief overview of reaction mechanism and experimental conditions. Two versions of the iridium-catalyzed allylic substitution have emerged. In type 1 reactions (introduced in 1997), linear allylic esters are commonly used as substrates under basic reaction conditions. In type 2 reactions (introduced in 2007), environmentally friendly branched allylic alcohols can be reacted under acidic conditions; occasionally, derivatives of allylic alcohols have also been applied. A unique feature of the type 2 reactions is that highly electrophilic allylic intermediates can be brought to reaction with weakly activated alkenes. The subsequent text is ordered according to the strategies followed to transform allylic substitution products to desired targets, most of which are natural products or drugs. Syntheses starting with an intermolecular allylic substitution are discussed first. Some fairly complex targets, for example, the potent nitric oxide inhibitor (-)-nyasol and the drug (-)-protrifenbute, have been synthesized via less than five steps from simple starting materials. Most targets discussed are cyclic compounds. Intermolecular allylic substitution with subsequent ring closing metathesis is a powerful strategy for their synthesis. Highlights are stereodivergent syntheses of Δ 9 -tetrahydrocannabinols (THC), wherein iridium- and organocatalysis are combined (dual catalysis). The combination of allylic alkylation with a Diels-Alder reaction was utilized to synthesize the ketide apiosporic acid and the drug fesoterodine (Toviaz). Sequential allylic amination, hydroboration and Suzuki-Miyaura coupling generates enones suitable for conjugate addition reactions; this strategy was employed in syntheses of a variety of alkaloids, for example, the poison frog alkaloid (+)-cis-195A (pumiliotoxin C). Intramolecular substitutions offer interesting possibilities to build up stereochemical complexity via short synthetic routes. For example, in diastereoselective cyclizations of chiral compounds, substrate control can be overruled by catalyst control in order to generate cis- and trans-isomers selectively from a given precursor. This approach was used to prepare a variety of piperidine and pyrrolidine alkaloids. Finally, complex polycyclic structures, including the structurally unusual indolosesquiterpenoid mycoleptodiscin A, have been generated diastereo- and enantioselectively from olefins by polyene cyclizations and from electron-rich arenes, such as indoles, in dearomatization reactions.

Controlled iterative cross-coupling: on the way to the automation of organic synthesis.

PubMed

Wang, Congyang; Glorius, Frank

2009-01-01

Repetition does not hurt! New strategies for the modulation of the reactivity of difunctional building blocks are discussed, allowing the palladium-catalyzed controlled iterative cross-coupling and, thus, the efficient formation of complex molecules of defined size and structure (see scheme). As in peptide synthesis, this development will enable the automation of these reactions. M(PG)=protected metal, M(act)=metal.

Structural studies on bioactive compounds. Part 29: palladium catalysed arylations and alkynylations of sterically hindered immunomodulatory 2-amino-5-halo-4,6-(disubstituted)pyrimidines.

PubMed

Hannah, D R; Sherer, E C; Davies, R V; Titman, R B; Laughton, C A; Stevens, M F

2000-04-01

The immunological agent bropirimine 5 is a tetra-substituted pyrimidine with anticancer and interferon-inducing properties. Synthetic routes to novel 5-aryl analogues of bropirimine have been developed and their potential molecular recognition properties analysed by molecular modelling methods. Sterically challenged 2-amino-5-halo-6-phenylpyrimidin-4-ones (halo = Br or I) are poor substrates for palladium catalysed Suzuki cross-coupling reactions with benzeneboronic acid because the basic conditions of the reaction converts the amphoteric pyrimidinones to their unreactive enolic forms. Palladium-mediated reductive dehalogenation of the pyrimidinone substrates effectively competes with cross-coupling. 2-Amino-5-halo-4-methoxy-6-phenylpyrimidines can be converted to a range of 5-aryl derivatives with the 5-iodopyrimidines being the most efficient substrates. Hydrolysis of the 2-amino-5-aryl-4-methoxy-6-phenylpyrimidines affords the required pyrimidin-4-ones in high yields. Semi-empirical quantum mechanical calculations show how the nature of the 5-substituent influences the equilibrium between the 1H- and 3H-tautomeric forms, and the rotational freedom about the bond connecting the 6-phenyl group and the pyrimidine ring. Both of these factors may influence the biological properties of these compounds.

Transition-metal-catalyzed direct arylation of (hetero)arenes by C-H bond cleavage.

PubMed

Ackermann, Lutz; Vicente, Rubén; Kapdi, Anant R

2009-01-01

The area of transition-metal-catalyzed direct arylation through cleavage of C-H bonds has undergone rapid development in recent years, and is becoming an increasingly viable alternative to traditional cross-coupling reactions with organometallic reagents. In particular, palladium and ruthenium catalysts have been described that enable the direct arylation of (hetero)arenes with challenging coupling partners--including electrophilic aryl chlorides and tosylates as well as simple arenes in cross-dehydrogenative arylations. Furthermore, less expensive copper, iron, and nickel complexes were recently shown to be effective for economically attractive direct arylations.

Palladium-Catalyzed Arylation of Fluoroalkylamines

PubMed Central

Brusoe, Andrew T.; Hartwig, John F.

2015-01-01

We report the synthesis of fluorinated anilines by palladium-catalyzed coupling of fluoroalkylamines with aryl bromides and aryl chlorides. The products of these reactions are valuable because anilines typically require the presence of an electron-withdrawing substituent on nitrogen to suppress aerobic or metabolic oxidation, and the fluoroalkyl groups have steric properties and polarity distinct from those of more common electron-withdrawing amide and sulfonamide units. The fluoroalkylaniline products are unstable under typical conditions for C–N coupling reactions (heat and strong base). However, the reactions conducted with the weaker base KOPh, which has rarely been used in cross-coupling to form C–N bonds, occurred in high yield in the presence of a catalyst derived from commercially available AdBippyPhos and [Pd(allyl)Cl]2. Under these conditions, the reactions occur with low catalyst loadings (<0.50 mol % for most substrates) and tolerate the presence of various functional groups that react with the strong bases that are typically used in Pd-catalyzed C–N cross-coupling reactions of aryl halides. The resting state of the catalyst is the phenoxide complex, (BippyPhosPd(Ar)OPh); due to the electron-withdrawing property of the fluoroalkyl substituent, the turnover-limiting step of the reaction is reductive elimination to form the C–N bond. PMID:26065341

Solution-phase parallel synthesis of hexahydro-1H-isoindolone libraries via tactical combination of Cu-catalyzed three-component coupling and Diels-Alder reactions.

PubMed

Zhang, Lei; Lushington, Gerald H; Neuenswander, Benjamin; Hershberger, John C; Malinakova, Helena C

2008-01-01

Parallel solution-phase synthesis of combinatorial libraries of hexahydro-1 H-isoindolones exploiting a novel "tactical combination" of Cu-catalyzed three-component coupling and Diels-Alder reactions was accomplished. Three distinct libraries consisting of 24 members (library I), 60 members (library II), and 32 members (library III) were constructed. Variation of three substituents on the isoindolone scaffold in library I was exclusively achieved by the choice of the building blocks. In the syntheses of libraries II and III, sublibraries of isoindolone scaffolds were prepared initially in a one-pot/two-step process and were further diversified via Pd-catalyzed Suzuki cross-coupling reaction with boronic acids at two different diversification points. The Lipinski profiles and calculated ADME properties of the compounds are also reported.

Diazo compounds and N-tosylhydrazones: novel cross-coupling partners in transition-metal-catalyzed reactions.

PubMed

Xiao, Qing; Zhang, Yan; Wang, Jianbo

2013-02-19

Transition-metal-catalyzed carbene transformations and cross-couplings represent two major reaction types in organometallic chemistry and organic synthesis. However, for a long period of time, these two important areas have evolved separately, with essentially no overlap or integration. Thus, an intriguing question has emerged: can cross-coupling and metal carbene transformations be merged into a single reaction cycle? Such a combination could facilitate the development of novel carbon-carbon bond-forming methodologies. Although this concept was first explored about 10 years ago, rapid developments inthis area have been achieved recently. Palladium catalysts can be used to couple diazo compounds with a wide variety of organic halides. Under oxidative coupling conditions, diazo compounds can also react with arylboronic acids and terminal alkynes. Both of these coupling reactions form carbon-carbon double bonds. As the key step in these catalytic processes, Pd carbene migratory insertion plays a vital role in merging the elementary steps of Pd intermediates, leading to novel carbon-carbon bond formations. Because the diazo substrates can be generated in situ from N-tosylhydrazones in the presence of base, the N-tosylhydrazones can be used as reaction partners, making this type of cross-coupling reaction practical in organic synthesis. N-Tosylhydrazones are easily derived from the corresponding aldehydes or ketones. The Pd-catalyzed cross-coupling of N-tosylhydrazones is considered a complementary reaction to the classic Shapiro reaction for converting carbonyl functionalities into carbon-carbon double bonds. It can also serve as an alternative approach for the Pd-catalyzed cross-coupling of carbonyl compounds, which is usually achieved via triflates. The combination of carbene formation and cross-coupling in a single catalytic cycle is not limited to Pd-catalyzed reactions. Recent studies of Cu-, Rh-, Ni-, and Co-catalyzed cross-coupling reactions with diazo compounds or N-tosylhydrazones show that these transformations also work with other transition metals, demonstrating the generality of the diazo compounds as new cross-coupling partners in transition-metal-catalyzed coupling reactions.

Controlled deposition of palladium nanodendrites on the tips of gold nanorods and their enhanced catalytic activity.

PubMed

Su, Gaoxing; Jiang, Huaqiao; Zhu, Hongyan; Lv, Jing-Jing; Yang, Guohai; Yan, Bing; Zhu, Jun-Jie

2017-08-31

Plasmonic Au-Pd nanostructures have drawn significant attention for use in heterogeneous catalysis. In this study, palladium nanodendrite-tipped gold nanorods (PdND-T-AuNRs) were subjected to a facile fabrication under mild reaction conditions. The palladium amounts on the two tips were tunable. In the preparation of PdND-T-AuNRs, dense capped AuNRs, a low reaction temperature, and suitable stabilizing agents were identified as critical reaction parameters for controlling palladium nanodendrites deposited on both ends of AuNRs. After overgrowth with palladium nanodendrites, the longitudinal surface plasmonic resonance peaks of PdND-T-AuNRs were red-shifted from 810 nm to 980 nm. The electrocatalytic activity of PdND-T-AuNRs for ethanol oxidation was examined, which was a bit weaker than that of cuboid core-shell Au-Pd nanodendrites; however, PdND-T-AuNRs were more stable in ethanol electrooxidation. Moreover, the photocatalytic activity of PdND-T-AuNRs for Suzuki cross-coupling reactions was investigated. At room temperature, nearly 100% yield was obtained under laser irradiation. The results can further enhance our capability of fine-tuning the optical, electronic, and catalytic properties of the bimetallic Au-Pd nanostructures.

Synthesis of aldehyde-linked nucleotides and DNA and their bioconjugations with lysine and peptides through reductive amination.

PubMed

Raindlová, Veronika; Pohl, Radek; Hocek, Michal

2012-03-26

5-(5-Formylthienyl)-, 5-(4-formylphenyl)- and 5-(2-fluoro-5-formylphenyl)cytosine 2'-deoxyribonucleoside mono- (dC(R)MP) and triphosphates (dC(R)TP) were prepared by aqueous Suzuki-Miyaura cross-coupling of 5-iodocytosine nucleotides with the corresponding formylarylboronic acids. The dC(R)TPs were excellent substrates for DNA polymerases and were incorporated into DNA by primer extension or PCR. Reductive aminations of the model dC(R)MPs with lysine or lysine-containing tripeptide were studied and optimized. In aqueous phosphate buffer (pH 6.7) the yields of the reductive aminations with tripeptide III were up to 25 %. Bioconjugation of an aldehyde-containing DNA with a lysine-containing tripeptide was achieved through reductive amination in yields of up to 90 % in aqueous phosphate buffer. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Pd-bound functionalized mesoporous silica as active catalyst for Suzuki coupling reaction: Effect of OAcˉ, PPh3 and Clˉ ligands on catalytic activity

NASA Astrophysics Data System (ADS)

Das, Trisha; Uyama, Hiroshi; Nandi, Mahasweta

2018-04-01

Three new palladium catalysts, PdCat-I, PdCat-II and PdCat-III, immobilized over heterogeneous silica support have been synthesized using different ligands attached to the palladium precursor. The ligands that have been used in this study are acetate, triphenylphosphine and chloride in PdCat-I, PdCat-II and PdCat-III, respectively. The ligands have different effect on stability of the compounds and impart different oxidation states to the metal center. The materials have been characterized by powder X-ray diffraction, nitrogen adsorption-desorption studies, transmission electron microscopy, thermal analysis, and different spectroscopic techniques. The Pd-content of the samples have been determined by ICP-AES analysis. The materials have been used as catalysts for Suzuki coupling reaction of aryl halides with phenylboronic acid under mild conditions. A comparative study has been carried out to ascertain the effect of the nature of different ligands on the outcome of the catalytic reactions. Products have been identified and estimated by 1H NMR and gas chromatography. The results show that the best yields are obtained with the catalyst containing triphenylphosphine as the ligand in methanol. Such type of work to study the effect of ligand on Suzuki coupling reaction over functionalized mesoporous silica heterogeneous catalysts have not been carried out so far.

Switching on elusive organometallic mechanisms with photoredox catalysis

NASA Astrophysics Data System (ADS)

Terrett, Jack A.; Cuthbertson, James D.; Shurtleff, Valerie W.; MacMillan, David W. C.

2015-08-01

Transition-metal-catalysed cross-coupling reactions have become one of the most used carbon-carbon and carbon-heteroatom bond-forming reactions in chemical synthesis. Recently, nickel catalysis has been shown to participate in a wide variety of C-C bond-forming reactions, most notably Negishi, Suzuki-Miyaura, Stille, Kumada and Hiyama couplings. Despite the tremendous advances in C-C fragment couplings, the ability to forge C-O bonds in a general fashion via nickel catalysis has been largely unsuccessful. The challenge for nickel-mediated alcohol couplings has been the mechanistic requirement for the critical C-O bond-forming step (formally known as the reductive elimination step) to occur via a Ni(III) alkoxide intermediate. Here we demonstrate that visible-light-excited photoredox catalysts can modulate the preferred oxidation states of nickel alkoxides in an operative catalytic cycle, thereby providing transient access to Ni(III) species that readily participate in reductive elimination. Using this synergistic merger of photoredox and nickel catalysis, we have developed a highly efficient and general carbon-oxygen coupling reaction using abundant alcohols and aryl bromides. More notably, we have developed a general strategy to `switch on' important yet elusive organometallic mechanisms via oxidation state modulations using only weak light and single-electron-transfer catalysts.

Switching on elusive organometallic mechanisms with photoredox catalysis.

PubMed

Terrett, Jack A; Cuthbertson, James D; Shurtleff, Valerie W; MacMillan, David W C

2015-08-20

Transition-metal-catalysed cross-coupling reactions have become one of the most used carbon-carbon and carbon-heteroatom bond-forming reactions in chemical synthesis. Recently, nickel catalysis has been shown to participate in a wide variety of C-C bond-forming reactions, most notably Negishi, Suzuki-Miyaura, Stille, Kumada and Hiyama couplings. Despite the tremendous advances in C-C fragment couplings, the ability to forge C-O bonds in a general fashion via nickel catalysis has been largely unsuccessful. The challenge for nickel-mediated alcohol couplings has been the mechanistic requirement for the critical C-O bond-forming step (formally known as the reductive elimination step) to occur via a Ni(III) alkoxide intermediate. Here we demonstrate that visible-light-excited photoredox catalysts can modulate the preferred oxidation states of nickel alkoxides in an operative catalytic cycle, thereby providing transient access to Ni(III) species that readily participate in reductive elimination. Using this synergistic merger of photoredox and nickel catalysis, we have developed a highly efficient and general carbon-oxygen coupling reaction using abundant alcohols and aryl bromides. More notably, we have developed a general strategy to 'switch on' important yet elusive organometallic mechanisms via oxidation state modulations using only weak light and single-electron-transfer catalysts.

Green heterogeneous Pd(II) catalyst produced from chitosan-cellulose micro beads for green synthesis of biaryls.

PubMed

Baran, Talat; Sargin, Idris; Kaya, Murat; Menteş, Ayfer

2016-11-05

In green catalyst systems, both the catalyst and the technique should be environmentally safe. In this study we designed a green palladium(II) catalyst for microwave-assisted Suzuki CC coupling reactions. The catalyst support was produced from biopolymers; chitosan and cellulose. The catalytic activity of the catalyst was tested on 16 substrates in solvent-free media and compared with those of commercial palladium salts. Reusability tests were done. The catalyst was also used in conventional reflux-heating system to demonstrate the efficiency of microwave heating method. We recorded high activity, selectivity and excellent TONs (6600) and TOFs (82500) just using a small catalyst loading (1.5×10(-3)mol%) in short reaction time (5min). The catalyst exhibited a long lifetime (9 runs). The findings indicated that both green chitosan/cellulose-Pd(II) catalyst and the microwave heating are suitable for synthesis of biaryl compounds by using Suzuki CC coupling reactions. Copyright © 2016 Elsevier Ltd. All rights reserved.

Tandem intramolecular silylformylation and silicon-assisted cross-coupling reactions. synthesis of geometrically defined alpha,beta-unsaturated aldehydes.

PubMed

Denmark, Scott E; Kobayashi, Tetsuya

2003-06-27

The palladium- and copper-catalyzed cross-coupling reactions of cyclic silyl ethers with aryl iodides are reported. Silyl ethers 3 were readily prepared by intramolecular silylformylation of homopropargyl silyl ethers 2 under a carbon monoxide atmosphere. The reaction of cyclic silyl ethers 3with various aryl iodides 7 in the presence of [(allyl)PdCl](2), CuI, a hydrosilane, and KF.2H(2)O in DMF at room temperature provided the alpha,beta-unsaturated aldehyde coupling products 8 in high yields. The need for copper in this process suggested that transmetalation from silicon to copper is an important step in the mechanism. Although siloxane 3 and the product 8 are not stable under basic conditions, KF.2H(2)O provided the appropriate balance of reactivity toward silicon and reduced basicity. The addition of a hydrosilane to [(allyl)PdCl](2) was needed to reduce the palladium(II) to the active palladium(0) form.

Efficient synthetic protocols in glycerol under heterogeneous catalysis.

PubMed

Cravotto, Giancarlo; Orio, Laura; Gaudino, Emanuela Calcio; Martina, Katia; Tavor, Dorith; Wolfson, Adi

2011-08-22

The massive increase in glycerol production from the transesterification of vegetable oils has stimulated a large effort to find novel uses for this compound. Hence, the use of glycerol as a solvent for organic synthesis has drawn particular interest. Drawbacks of this green and renewable solvent are a low solubility of highly hydrophobic molecules and a high viscosity, which often requires the use of a fluidifying co-solvent. These limitations can be easily overcome by performing reactions under high-intensity ultrasound and microwaves in a stand-alone or combined manner. These non-conventional techniques facilitate and widen the use of glycerol as a solvent in organic synthesis. Glycerol allows excellent acoustic cavitation even at high temperatures (70-100 °C), which is otherwise negligible in water. Herein, we describe three different types of applications: 1) the catalytic transfer hydrogenation of benzaldehyde to benzyl alcohol in which glycerol plays the dual role of the solvent and hydrogen donor; 2) the palladium-catalyzed Suzuki cross-coupling; and (3) the Barbier reaction. In all cases glycerol proved to be a greener, less expensive, and safer alternative to the classic volatile organic solvents. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Enantio-Relay Catalysis Constructs Chiral Biaryl Alcohols over Cascade Suzuki Cross-Coupling-Asymmetric Transfer Hydrogenation

NASA Astrophysics Data System (ADS)

Zhang, Dacheng; Gao, Xiaoshuang; Cheng, Tanyu; Liu, Guohua

2014-05-01

The construction of chiral biaryl alcohols using enantio-relay catalysis is a particularly attractive synthetic method in organic synthesis. However, overcoming the intrinsic incompatibility of distinct organometallic complexes and the reaction conditions used are significant challenges in asymmetric catalysis. To overcome these barriers, we have taken advantage of an enantio-relay catalysis strategy and a combined dual-immobilization approach. We report the use of an imidazolium-based organopalladium-functionalized organic-inorganic hybrid silica and ethylene-coated chiral organoruthenium-functionalized magnetic nanoparticles to catalyze a cascade Suzuki cross-coupling-asymmetric transfer hydrogenation reaction to prepare chiral biaryl alcohols in a two-step, one-pot process. As expected, the site-isolated active species, salient imidazolium phase-transfer character and high ethylene-coated hydrophobicity can synergistically boost the catalytic performance. Furthermore, enantio-relay catalysis has the potential to efficiently prepare a variety of chiral biaryl alcohols. Our synthetic strategy is a general method that shows the potential of developing enantio-relay catalysis towards environmentally benign and sustainable organic synthesis.

Efficient one-step Suzuki arylation of unprotected halonucleosides, using water-soluble palladium catalysts.

PubMed

Western, Elizabeth C; Daft, Jonathan R; Johnson, Edward M; Gannett, Peter M; Shaughnessy, Kevin H

2003-08-22

Modification of nucleosides to give pharmaceutically active compounds, mutagenesis models, and oligonucleotide structural probes continues to be of great interest. The aqueous-phase modification of unprotected halonucleosides is reported herein. Using a catalyst derived from tris(3-sulfonatophenyl)phosphine (TPPTS) and palladium acetate, 8-bromo-2'-deoxyguanosine (8-BrdG) is coupled with arylboronic acids to give 8-aryl-2'-deoxyguanosine adducts (8-ArdG) in excellent yield in a 2:1 water:acetonitrile solvent mixture. The TPPTS ligand was found to be superior to water-soluble alkylphosphines for this coupling reaction. The coupling chemistry has been extended to 8-bromo-2'-deoxyadenosine (8-BrdA) and 5-iodo-2'-deoxyuridine (5-IdU), as well as the ribonucleosides 8-bromoguanosine and 8-bromoadenosine. Good to excellent yields of arylated adducts are obtained in all cases. With use of tri(4,6-dimethyl-3-sulfonatophenyl)phosphine (TXPTS), the Suzuki coupling of 8-BrdA and 5-IdU can be accomplished in less than 1 h at room temperature. This methodology represents an efficient and general method for halonucleoside arylation that does not require prior protection of the nucleoside.

Synthesis of Unsymmetrical 3,4-Diaryl-3-pyrrolin-2-ones Utilizing Pyrrole Weinreb Amides

PubMed Central

Greger, Jessica G.; Yoon-Miller, Sarah J.P.; Bechtold, Nathan R.; Flewelling, Scott A.; MacDonald, Jacob P.; Downey, Catherine R.; Cohen, Eric A.; Pelkey, Erin T.

2011-01-01

A regiocontrolled synthesis of unsymmetrical 3,4-diaryl-3-pyrrolin-2-ones has been achieved in three steps from 1,2-diaryl-1-nitroethenes with pyrrole-2-carboxamides (pyrrole Weinreb amides) serving as the key linchpin intermediates. Two different methods for the preparation of the requisite nitroalkenes were investigated: (1) modified Henry reaction between arylnitromethanes and arylimines; and (2) Suzuki-Miyaura cross-coupling reaction of 2-aryl-1-bromo-1-nitroethenes with arylboronic acids. Some difficulty was encountered in the preparation of arylnitromethanes, thus leading to the exploration of a cross-coupling strategy that proved more useful. A Barton-Zard pyrrole cyclocondensation reaction between 1,2-diaryl-1-nitroethenes and N-methoxy-N-methyl-2-isocyanoacetamide gave the corresponding pyrrole Weinreb amides, which were then converted into the desired 3-pyrrolin-2-ones in two steps. Overall, this method allowed for the construction of 3,4-diaryl-3-pyrrolin-2-ones with complete regiocontrol of the substituents with respect to the lactam carbonyl. The utility of this synthetic methodology was demonstrated by the preparation of eight unsymmetrical and symmetrical 3,4-diaryl-3-pyrrolin-2-ones including the N-H lactam analog of the selective COX-II inhibitor, rofecoxib. PMID:21913662

Impact of linker engineering on the catalytic activity of metal–organic frameworks containing Pd(II)–bipyridine complexes

DOE PAGES

Li, Xinle; Van Zeeland, Ryan; Maligal-Ganesh, Raghu V.; ...

2016-08-09

A series of mixed-linker bipyridyl metal–organic framework (MOF)-supported palladium(II) catalysts were used to elucidate the electronic and steric effects of linker substitution on the activity of these catalysts in the context of Suzuki–Miyaura cross-coupling reactions. m-6,6'-Me 2bpy-MOF-PdCl 2 exhibited 110- and 496-fold enhancements in activity compared to nonfunctionalized m-bpy-MOF-PdCl 2 and m-4,4'-Me 2bpy-MOF-PdCl 2, respectively. Furthermore, this result clearly demonstrates that the stereoelectronic properties of metal-binding linker units are critical to the activity of single-site organometallic catalysts in MOFs and highlights the importance of linker engineering in the design and development of efficient MOF catalysts.

Palladium Nanoparticle-Loaded Cellulose Paper: A Highly Efficient, Robust, and Recyclable Self-Assembled Composite Catalytic System.

PubMed

Zheng, Guangchao; Kaefer, Katharina; Mourdikoudis, Stefanos; Polavarapu, Lakshminarayana; Vaz, Belén; Cartmell, Samantha E; Bouleghlimat, Azzedine; Buurma, Niklaas J; Yate, Luis; de Lera, Ángel R; Liz-Marzán, Luis M; Pastoriza-Santos, Isabel; Pérez-Juste, Jorge

2015-01-15

We present a novel strategy based on the immobilization of palladium nanoparticles (Pd NPs) on filter paper for development of a catalytic system with high efficiency and recyclability. Oleylamine-capped Pd nanoparticles, dispersed in an organic solvent, strongly adsorb on cellulose filter paper, which shows a great ability to wick fluids due to its microfiber structure. Strong van der Waals forces and hydrophobic interactions between the particles and the substrate lead to nanoparticle immobilization, with no desorption upon further immersion in any solvent. The prepared Pd NP-loaded paper substrates were tested for several model reactions such as the oxidative homocoupling of arylboronic acids, the Suzuki cross-coupling reaction, and nitro-to-amine reduction, and they display efficient catalytic activity and excellent recyclability and reusability. This approach of using NP-loaded paper substrates as reusable catalysts is expected to open doors for new types of catalytic support for practical applications.

How low does iron go? Chasing the active species in fe-catalyzed cross-coupling reactions.

PubMed

Bedford, Robin B

2015-05-19

The catalytic cross-coupling reactions of organic halides or related substrates with organometallic nucleophiles form the cornerstone of many carbon-carbon bond-forming processes. While palladium-based catalysts typically mediate such reactions, there are increasing concerns about the long-term sustainability of palladium in synthesis. This is due to the high cost of palladium, coupled with its low natural abundance, environmentally deleterious extraction (∼6 g of metal are produced per ton of ore), toxicity, and competition for its use from the automotive and consumer electronics sectors. Therefore, there is a growing interest in replacing palladium-based catalysts with those incorporating more earth-abundant elements. With its low cost, high natural abundance, and low toxicity, iron makes a particularly appealing alternative, and accordingly, the development of iron-catalyzed cross-coupling is undergoing explosive growth. However, our understanding of the mechanisms that underpin the iron-based catalytic cycles is still very much in its infancy. Mechanistic insight into catalytic reactions is not only academically important but also allows us to maximize the efficiency of processes or even to develop entirely new transformations. Key to the development of robust mechanistic models for cross-coupling is knowing the lowest oxidation state in the cycle. Once this is established, we can explore subsequent redox processes and build the catalytic manifold. Until we know with confidence what the lowest oxidation state is, any cycles proposed are largely just guesswork. To date, Fe(-II), Fe(-I), Fe(0), Fe(I), and Fe(II) have been proposed as contenders for the lowest-oxidation-state species in the cycle in iron-catalyzed cross-coupling; the aim of this Account is to pull together the various pieces of evidence in support, or otherwise, of each of these suggestions in turn. There currently exists no direct evidence that oxidation states below Fe(0) are active in the catalytic cycle. Meanwhile, the reactivity required of the lowest-oxidation-state species has been observed with model compounds in higher oxidation states, implying that there is no need to invoke such low oxidation states. While subzero-valent complexes do indeed act as effective precatalysts, it is important to recognize that this tells us that they are efficiently converted to an active catalyst but says nothing about the oxidation states of the species in the catalytic cycle. Zero-valent heterogeneous iron nanoparticles can be formed under typical catalytic conditions, but there is no evidence to suggest that homogeneous Fe(0) complexes can be produced under comparable conditions. It seems likely that the zero-valent nanoparticles act as a reservoir for soluble higher-oxidation-state species. Fe(II) complexes can certainly be formed under catalytically relevant conditions, and when bulky nucleophilic coupling partners are exploited, potential intermediates can be isolated. However, the bulky reagents act as poor proxies for most nucleophiles used in cross-coupling, as they give Fe(II) organometallic intermediates that are kinetically stabilized with respect to reductive elimination. When more realistic substrates are exploited, reduction or disproportionation to Fe(I) is widely observed, and while it still has not been conclusively proved, this oxidation state currently represents a likely candidate for the lowest one active in many iron-catalyzed cross-coupling processes.

Palladium-catalyzed cross coupling reactions of 4-bromo-6H-1,2-oxazines

PubMed Central

Schmidt, Elmar; Andrä, Michal; Duhs, Marcel-Antoine; Linder, Igor

2009-01-01

Summary A number of 4-aryl- and 4-alkynyl-substituted 6H-1,2-oxazines 8 and 9 have been prepared in good yields via cross coupling reactions of halogenated precursors 2, which in turn are easily accessible by bromination of 6H-1,2-oxazines 1. Lewis-acid promoted reaction of 1,2-oxazine 9c with 1-hexyne provided alkynyl-substituted pyridine derivative 12 thus demonstrating the potential of this approach for the synthesis of pyridines. PMID:19936264

Self-assembly of triangular metallomacrocycles using unsymmetrical bisterpyridine ligands: isomer differentiation via TWIM mass spectrometry.

PubMed

Liang, Yen-Peng; He, Yun-Jui; Lee, Yin-Hsuan; Chan, Yi-Tsu

2015-03-21

Three unsymmetrical, 60°-bended bisterpyridine ligands with varying phenylene spacer lengths have been synthesized via the Suzuki-Miyaura coupling reactions. Their self-assembly processes were found to be strongly dependent on the ligand geometry. Upon complexation with Zn(II) ions, only 2,4''-di(4'-terpyridinyl)-1,1':4',1''-terphenyl underwent self-selection to give a trinuclear metallomacrocycle with perfect heteroleptic connectivity and the other two afforded a mixture of constitutional isomers. The metallosupramolecular assemblies were characterized by NMR spectroscopy, electrospray mass spectrometry (ESI MS), and single-crystal X-ray diffraction. In particular, the identification of isomeric architecture was accomplished using tandem mass spectrometry (MS(2)) coupled with traveling wave ion mobility mass spectrometry (TWIM MS).

Synthesis of 5-iodo-1,2,3-triazole-containing macrocycles using copper flow reactor technology.

PubMed

Bogdan, Andrew R; James, Keith

2011-08-05

A new macrocyclization strategy to synthesize 12- to 31-membered 5-iodo-1,2,3-triazole-containing macrocycles is described. The macrocycles have been generated using a simple and efficient copper-catalyzed cycloaddition in flow under environmentally friendly conditions. This methodology also permits the facile, regioselective synthesis of 1,4,5-trisubstituted-1,2,3-triazole-containing macrocyles using palladium-catalyzed cross-coupling reactions. © 2011 American Chemical Society

Palladium complexes of N-heterocyclic carbenes as catalysts for cross-coupling reactions--a synthetic chemist's perspective.

PubMed

Kantchev, Eric Assen B; O'Brien, Christopher J; Organ, Michael G

2007-01-01

Palladium-catalyzed C-C and C-N bond-forming reactions are among the most versatile and powerful synthetic methods. For the last 15 years, N-heterocyclic carbenes (NHCs) have enjoyed increasing popularity as ligands in Pd-mediated cross-coupling and related transformations because of their superior performance compared to the more traditional tertiary phosphanes. The strong sigma-electron-donating ability of NHCs renders oxidative insertion even in challenging substrates facile, while their steric bulk and particular topology is responsible for fast reductive elimination. The strong Pd-NHC bonds contribute to the high stability of the active species, even at low ligand/Pd ratios and high temperatures. With a number of commercially available, stable, user-friendly, and powerful NHC-Pd precatalysts, the goal of a universal cross-coupling catalyst is within reach. This Review discusses the basics of Pd-NHC chemistry to understand the peculiarities of these catalysts and then gives a critical discussion on their application in C-C and C-N cross-coupling as well as carbopalladation reactions.

Synthesis and structural and photoswitchable properties of novel chiral host molecules: axis chiral 2,2'-dihydroxy-1,1'-binaphthyl-appended stiff-stilbene.

PubMed

Shimasaki, Toshiaki; Kato, Shin-ichiro; Ideta, Keiko; Goto, Kenta; Shinmyozu, Teruo

2007-02-16

Novel photoswitchable chiral hosts having an axis chiral 2,2'-dihydroxy-1,1'-binaphthyl (BINOL)-appended stiff-stilbene, trans-(R,R)- and -(S,S)-1, were synthesized by palladium-catalyzed Suzuki-Miyaura coupling and low-valence titanium-catalyzed McMurry coupling as key steps, and they were fully characterized by various NMR spectral techniques. The enantiomers of trans-1 showed almost complete mirror images in the CD spectra, where two split Cotton effects (exciton coupling) were observed in the beta-transitions of the naphthyl chromophore at 222 and 235 nm, but no Cotton effect was observed in the stiff-stilbene chromophore at 365 nm. The structures of (R)-10 and trans-(R,R)-1 were confirmed by X-ray structural analysis. The optimized structure of cis-1 by MO calculations has a wide chiral cavity of 7-8 A in diameter, whereas trans-1 cannot form an intramolecular cavity based on the X-ray data. Irradiation of (R,R)-trans-1 with black light (lambda = 365 nm) in CH3CN or benzene at 23 degrees C led to the conversion to the corresponding cis-isomer, as was monitored by 1H NMR, UV-vis, and CD spectra. At the photostationary state, the cis-1/trans-1 ratio was 86/14 in benzene or 75/25 in CH3CN. On the other hand, irradiation of the cis-1/trans-1 (75/25) mixture in CH3CN with an ultra-high-pressure Hg lamp at 23 degrees C (lambda = 410 nm) led to the photostationary state, where the cis-1/trans-1 ratio was estimated to be 9/91 on the basis of the 1H NMR spectra. The cis-trans and trans-cis interconversions could be repeated 10 times without decomposition of the C=C double bond. Thus, a new type of photoswitchable molecule has been developed, and trans-1 and cis-1 were quite durable under irradiation conditions. The guest binding properties of the BINOL moieties of trans- and cis-(R,R)-1 with F-, Cl-, and H2PO4- were examined by 1H NMR titration in CDCl3. Similar interaction with F- and Cl- was observed in trans-1 (host/guest = 1/1, Kassoc = (1.0 +/- 0.13) x 103 for F- and (4.6 +/- 0.72) x 102 M-1 for Cl-) and cis-1 (host/guest = 1/1, Kassoc = (1.0 +/- 0.13) x 103 for F- and (5.9 +/- 0.69) x 10 M-1 for Cl-), but H2PO4- interacted differently: the cis-isomer formed the 1/1 complex (Kassoc = (9.38 +/- 2.67) x 10 M-1), whereas multistep equilibrium was expected for the trans-isomer.

Development of 1-aryl-3-furanyl/thienyl-imidazopyridine templates for inhibitors against hypoxia inducible factor (HIF)-1 transcriptional activity.

PubMed

Fuse, Shinichiro; Ohuchi, Toshiaki; Asawa, Yasunobu; Sato, Shinichi; Nakamura, Hiroyuki

2016-12-15

1,3-Disubstituted-imidazopyridines were designed for developing inhibitors against HIF-1 transcriptional activity. Designed compounds were rapidly synthesized from a key aromatic scaffold via microwave-assisted Suzuki-Miyaura coupling/CH direct arylation sequence. Evaluation of ability to inhibit the hypoxia induced transcriptional activity of HIF-1 revealed that the compound 2i and 3a retained the same level of the inhibitory activity comparing with that of known inhibitor, YC-1 (1). Identified, readily accessible 1-aryl-3-furanyl/thienyl-imidazopyridine templates should be useful for future drug development. Copyright © 2016 Elsevier Ltd. All rights reserved.

Preparation of dibenzo[e,g]isoindol-1-ones via Scholl-type oxidative cyclization reactions.

PubMed

van Loon, Amy A; Holton, Maeve K; Downey, Catherine R; White, Taryn M; Rolph, Carly E; Bruening, Stephen R; Li, Guanqun; Delaney, Katherine M; Pelkey, Sarah J; Pelkey, Erin T

2014-09-05

A flexible synthesis of dibenzo[e,g]isoindol-1-ones has been developed. Dibenzo[e,g]isoindol-1-ones represent simplified benzenoid analogues of biological indolo[2,3-a]pyrrolo[3,4-c]carbazol-5-ones (indolocarbazoles), compounds that have demonstrated a wide range of biological activity. The synthesis of the title compounds involved tetramic acid sulfonates. Different aryl groups were introduced at C4 of the heterocyclic ring via Suzuki-Miyaura cross-coupling reactions. Finally, mild Scholl-type oxidative cyclizations mediated by phenyliodine(III) bis(trifluoroacetate) (PIFA) converted some of the latter compounds into the corresponding dibenzo[e,g]isoindol-1-ones. A systematic study of the oxidative cyclization revealed the following reactivity trend: 3,4-dimethoxyphenyl ≫ 3-methoxyphenyl > 3,4,5-trimethoxyphenyl > 4-methoxyphenyl ≈ phenyl. Overall, the oxidative cyclization required at least two methoxy groups distributed in the aromatic rings, at least one of which had to be located para to the site of the cyclization.

Resting State and Elementary Steps of the Coupling of Aryl Halides with Thiols Catalyzed by Alkylbisphosphine Complexes of Palladium

PubMed Central

Alvaro, Elsa

2010-01-01

Detailed mechanistic studies on the coupling of aryl halides with thiols catalyzed by palladium complexes of the alkylbisphosphine ligand CyPF-tBu (1-dicyclohexylphosphino-2-di-tert-butylphosphinoethylferrocene) are reported. The elementary steps that constitute the catalytic cycle, i.e. oxidative addition, transmetalation and reductive elimination, have been studied, and their relative rates are reported. Each of the steps of the catalytic process occurs at temperatures that are much lower than those required for the reactions catalyzed by a combination of palladium precursors and CyPF-tBu. To explain these differences in rates between the catalytic and stoichiometric reactions, studies were conducted to identify the resting state of the catalyst of the reactions catalyzed by a combination of Pd(OAc)2 and CyPF-tBu, a combination of Pd(dba)2 and CyPF-tBu, or the likely intermediate Pd(CyPF-tBu)(Ar)(Br). These show that the major palladium complex in each case lies off of the catalytic cycle. The resting state of the reactions catalyzed by Pd(OAc)2 and CyPF-tBu was the palladium bis-thiolate complex [Pd(CyPF-tBu)(SR)2] (R = alkyl or aryl). The resting state in reactions catalyzed by Pd2(dba)3 and CyPF-tBu was the binuclear complex [Pd(CyPF-tBu)]2(μ2, η2-dba) (9). The resting state of reactions of both aromatic and aliphatic thiols catalyzed by [Pd(CyPF-tBu)(p-tolyl)(Br)] (3a) was the hydridopalladium thiolate complex [Pd(CyPF-tBu)(H)(SR)] (R= alkyl and aryl). All these palladium species have been prepared independently, and the mechanisms by which they enter the catalytic cycle have been examined in detail. These features of the reaction catalyzed by palladium and CyPF-tBu have been compared with those of reactions catalyzed by the alkylbisphosphine DiPPF and Pd(OAc)2 or Pd(dba)2. Our data indicate that the resting states of these reactions are similar to each other and that our mechanistic conclusions about reactions catalyzed by palladium and CyPF-tBu can be extrapolated to reactions catalyzed by complexes of other electron-rich bisphosphines. PMID:19453106

Palladium-Catalyzed Indole, Pyrrole, and Furan Arylation by Aryl Chlorides

PubMed Central

Nadres, Enrico T.; Lazareva, Anna; Daugulis, Olafs

2011-01-01

The palladium-catalyzed direct arylation of indoles, pyrroles, and furans by aryl chlorides has been demonstrated. The method employs a palladium acetate catalyst, 2-(dicyclohexylphosphino)-biphenyl ligand, and an inorganic base. Electron-rich and electron-poor aryl chlorides as well as chloropyridine coupling partners can be used and arylated heterocycles are obtained in moderate to good yields. Optimization of base, ligand, and solvent is required for achieving best results. PMID:21192652

Cu/Mn bimetallic catalysis enables carbonylative Suzuki-Miyaura coupling with unactivated alkyl electrophiles.

PubMed

Pye, Dominic R; Cheng, Li-Jie; Mankad, Neal P

2017-07-01

A bimetallic system consisting of Cu-carbene and Mn-carbonyl co-catalysts was employed for carbonylative C-C coupling of arylboronic esters with alkyl halides, allowing for the convergent synthesis of ketones. The system operates under mild conditions and exhibits complementary reactivity to Pd catalysis. The method is compatible with a wide range of arylboronic ester nucleophiles and proceeds smoothly for both primary and secondary alkyl iodide electrophiles. Preliminary mechanistic experiments corroborate a hypothetical catalytic mechanism consisting of co-dependent cycles wherein the Cu-carbene co-catalyst engages in transmetallation to generate an organocopper nucleophile, while the Mn-carbonyl co-catalyst activates the alkyl halide electrophile by single-electron transfer and then undergoes reversible carbonylation to generate an acylmanganese electrophile. The two cycles then intersect with a heterobimetallic, product-releasing C-C coupling step.

Total synthesis of (+/-)-strychnine via a [4 + 2]-cycloaddition/rearrangement cascade.

PubMed

Zhang, Hongjun; Boonsombat, Jutatip; Padwa, Albert

2007-01-18

A new strategy for the synthesis of the Strychnos alkaloid (+/-)-strychnine has been developed and is based on an intramolecular [4 + 2]-cycloaddition/rearrangement cascade of an indolyl-substituted amidofuran. The critical D-ring was assembled by an intramolecular palladium-catalyzed enolate-driven cross-coupling of an N-tethered vinyl iodide. [reaction: see text].

Total Synthesis of (±)-Strychnine via a [4+2]-Cycloaddition/Rearrangement Cascade

PubMed Central

Zhang, Hongjun; Boonsombat, Jutatip

2008-01-01

A new strategy for the synthesis of the Strychnos alkaloid (±)-strychnine has been developed and is based on an intramolecular [4+2]-cycloaddition/rearrangement cascade of an indolyl substituted amidofuran. The critical D-ring was assembled by an intramolecular palladium catalyzed enolate-driven cross-coupling of an N-tethered vinyl iodide. PMID:17217284

Novel guanosine-cytidine dinucleoside that self-assembles into a trimeric supramolecule.

PubMed

Sessler, Jonathan L; Jayawickramarajah, Janarthanan; Sathiosatham, Muhunthan; Sherman, Courtney L; Brodbelt, Jennifer S

2003-07-24

[reaction: see text] Synthesis and assembly studies of a guanosine-cytidine dinucleoside 1 that self-assembles into a trimeric supramolecule (I) are presented. Dinucleoside 1 was obtained by utilizing two consecutive palladium-catalyzed cross-coupling reactions. Ensemble I was analyzed by ESI-MS, NMR spectroscopies, size exclusion chromatography (SEC), and vapor pressure osmometry (VPO).

Surface-active ionic liquids for palladium-catalysed cross coupling in water: effect of ionic liquid concentration on the catalytically active species† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c7ra07757b

PubMed Central

Taskin, Meltem; Cognigni, Alice; Zirbs, Ronald; Reimhult, Erik

2017-01-01

We report the design and synthesis of surface-active ionic liquids for application in palladium-catalyzed cross coupling reactions. A series of dodecylimidazolium-based ionic liquids were applied as additives in the Heck reaction of ethyl acrylate and iodobenzene, and high yields of >90% could be obtained in water without the addition of further ligands. Our results indicate that the ionic liquid concentration in water is the key factor affecting the formation of the catalytically active species and hence the yield. Moreover, imidazolium-based ionic liquids that are able to form a carbene species differ significantly from conventional cationic surfactants, as a concentration dependent formation of the N-heterocyclic carbene complex was observed. PMID:29308189

2-Substituted 7-trifluoromethyl-thiadiazolopyrimidones as alkaline phosphatase inhibitors. Synthesis, structure activity relationship and molecular docking study.

PubMed

Jafari, Behzad; Ospanov, Meirambek; Ejaz, Syeda Abida; Yelibayeva, Nazym; Khan, Shafi Ullah; Amjad, Sayyeda Tayyeba; Safarov, Sayfidin; Abilov, Zharylkasyn A; Turmukhanova, Mirgul Zh; Kalugin, Sergey N; Ehlers, Peter; Lecka, Joanna; Sévigny, Jean; Iqbal, Jamshed; Langer, Peter

2018-01-20

Alkaline Phosphatases (APs) play a key role in maintaining a ratio of phosphate to inorganic pyrophosphate (P i /PP i ) and thus regulate extracellular matrix calcification during bone formation and growth. Among different isozymes of AP, aberrant increase in the level of tissue non-specific alkaline phosphatase (TNAP) is strongly associated with vascular calcification and end-stage renal diseases. In this context, we synthesized a novel series of fluorinated pyrimidone derivatives, i.e., 2-bromo-7-trifluoromethyl-5-oxo-5H-1,3,4-thiadiazolepyrimidones. The bromine functionality was further used for derivatisation by nucleophilic aromatic substitution using amines as nucleophiles as well as by Palladium catalysed Suzuki-Miyaura reactions. The synthesized derivatives were found potent but non-selective inhibitors of both isozymes of AP. Arylated thiadiazolopyrimidones exhibited stronger inhibitory activities than 2-amino-thiadiazolopyrimidones. The binding modes and possible interactions of the most active inhibitor within the active site of the enzyme were observed by molecular docking studies. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Cross-couplings in the elaboration of luminescent bis-terpyridyl iridium complexes: the effect of extended or inhibited conjugation on emission.

PubMed

Leslie, Wendy; Batsanov, Andrei S; Howard, Judith A K; Williams, J A Gareth

2004-02-21

The utility of Suzuki cross-coupling methodology for the in situ elaboration of bromo-functionalised bis-terpyridyl iridium(III) complexes has been explored. The complex [Ir(tpy)(tpy-phi-Br)]3+ [tpy-phi-Br = 4'-(4-bromophenyl)-2,2':6',2''-terpyridine] undergoes palladium-catalysed cross-coupling with aryl boronic acids to yield biaryl-substituted complexes directly. The biphenyl and 4-cyanobiphenyl-substituted products display relatively intense, long-lived (tau > 100 mus) yellow emission in degassed aqueous solution at room temperature, assigned to a 3pi-pi* state. A 4-aminobiphenyl-substituted analogue displays an additional low energy absorbance band, attributed to an intraligand charge-transfer (ILCT) excited state, and is scarcely emissive under the same conditions. The iridium(III) complex of 4'-mesityl-terpyridine is also reported. Its emission is much shorter-lived, with a spectral profile resembling that of unsubstituted [Ir(tpy)2]3+, confirming the need for the attainment of a roughly coplanar geometry for stabilisation of the 3pi-pi* excited state.

Construction of substituted benzene rings by palladium-catalyzed direct cross-coupling of olefins: a rapid synthetic route to 1,4-naphthoquinone and its derivatives.

PubMed

Hu, Peng; Huang, Shijun; Xu, Jing; Shi, Zhang-Jie; Su, Weiping

2011-10-10

Ring the changes: the direct cross-coupling of electron-deficient 1,4-benzoquinone or its derivatives with electron-rich alkyl vinyl ethers proceeds in a tandem manner to produce substituted benzene rings with good selectivity and in good to excellent yields. The reaction has the potential for the rapid synthesis of diverse substituted benzene rings as it is not limited by substituent effects. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Cobalt-catalyzed cross-coupling reactions of alkyl halides with allylic and benzylic Grignard reagents and their application to tandem radical cyclization/cross-coupling reactions.

PubMed

Ohmiya, Hirohisa; Tsuji, Takashi; Yorimitsu, Hideki; Oshima, Koichiro

2004-11-05

Details of cobalt-catalyzed cross-coupling reactions of alkyl halides with allylic Grignard reagents are disclosed. A combination of cobalt(II) chloride and 1,2-bis(diphenylphosphino)ethane (DPPE) or 1,3-bis(diphenylphosphino)propane (DPPP) is suitable as a precatalyst and allows secondary and tertiary alkyl halides--as well as primary ones--to be employed as coupling partners for allyl Grignard reagents. The reaction offers a facile synthesis of quaternary carbon centers, which has practically never been possible with palladium, nickel, and copper catalysts. Benzyl, methallyl, and crotyl Grignard reagents can all couple with alkyl halides. The benzylation definitely requires DPPE or DPPP as a ligand. The reaction mechanism should include the generation of an alkyl radical from the parent alkyl halide. The mechanism can be interpreted in terms of a tandem radical cyclization/cross-coupling reaction. In addition, serendipitous tandem radical cyclization/cyclopropanation/carbonyl allylation of 5-alkoxy-6-halo-4-oxa-1-hexene derivatives is also described. The intermediacy of a carbon-centered radical results in the loss of the original stereochemistry of the parent alkyl halides, creating the potential for asymmetric cross-coupling of racemic alkyl halides.

Nitroethylation of Vinyl Triflates and Bromides

PubMed Central

Padilla–Salinas, Rosaura; Walvoord, Ryan R.; Tcyrulnikov, Sergei

2013-01-01

A two-carbon homologation of vinyl triflates and bromides for the synthesis of homoallylic nitro products is described. This palladium-catalyzed double coupling of nitromethane exploits the anion stabilizing and leaving group properties of nitromethane, generating the homo allyl nitro products via a tandem cross-coupling/π-allylation sequence. The resultant process provides a mild and convenient entry of nitroethylated products, which are versatile precursors to β,γ-unsaturated carbonyls, homoallylic amines, and nitrile oxides. PMID:23885976

Single-step synthesis of styryl phosphonic acids via palladium-catalyzed Heck coupling of vinyl phosphonic acid with aryl halides

DOE PAGES

McNichols, Brett W.; Koubek, Joshua T.; Sellinger, Alan

2017-10-27

Here, we have developed a single step palladium-catalyzed Heck coupling of aryl halides with vinyl phosphonic acid to produce functionalized (E)-styryl phosphonic acids. This pathway utilizes a variety of commercially available aryl halides, vinyl phosphonic acid and Pd(P(tBu) 3) 2 as catalyst. These conditions produce a wide range of styryl phosphonic acids with high purities and good to excellent yields (31–80%).

Single-step synthesis of styryl phosphonic acids via palladium-catalyzed Heck coupling of vinyl phosphonic acid with aryl halides

DOE Office of Scientific and Technical Information (OSTI.GOV)

McNichols, Brett W.; Koubek, Joshua T.; Sellinger, Alan

Here, we have developed a single step palladium-catalyzed Heck coupling of aryl halides with vinyl phosphonic acid to produce functionalized (E)-styryl phosphonic acids. This pathway utilizes a variety of commercially available aryl halides, vinyl phosphonic acid and Pd(P(tBu) 3) 2 as catalyst. These conditions produce a wide range of styryl phosphonic acids with high purities and good to excellent yields (31–80%).

Palladium-catalyzed, pyrrolidine-mediated arylmethylation of ketones and aldehydes with coumarinyl(methyl) acetates.

PubMed

Cattopadhyay, Kalicharan; Recio, Antonio; Tunge, Jon A

2012-09-14

We report the palladium-catalyzed, pyrrolidine-mediated α-benzylation of enamines generated from aldehydes and ketones. The method allows for direct coupling of medicinally relevant coumarin moieties with aldehydes and ketones in good yield under mild conditions. The reaction is believed to proceed via a Pd-π-benzyl complex generated from (coumarinyl)methyl acetates.

Palladium-catalyzed, pyrrolidine-mediated arylmethylation of ketones and aldehydes with coumarinyl(methyl) acetates†

PubMed Central

Cattopadhyay, Kalicharan; Recio, Antonio; Tunge, Jon A.

2012-01-01

We report the palladium-catalyzed, pyrrolidine-mediated α-benzylation of enamines generated from aldehydes and ketones. The method allows for direct coupling of medicinally relevant coumarin moieties with aldehydes and ketones in good yield under mild conditions. The reaction is believed to proceed via a Pd-π-benzyl complex generated from (coumarinyl)methyl acetates. PMID:22832549

Synthesis, coordination and catalytic use of 1-(diphenylphosphino)-1'-carbamoylferrocenes with pyridyl-containing N-substituents.

PubMed

Kühnert, Janett; Dusek, Michal; Demel, Jan; Lang, Heinrich; Stepnicka, Petr

2007-07-14

Ferrocene phosphinocarboxamides, 1-(diphenylphosphino)-1'-{N-[(2-pyridyl)methyl]carbamoyl}ferrocene (1) and 1-(diphenylphosphino)-1'-{N-[2-(2-pyridyl)ethyl]carbamoyl}ferrocene (2) were prepared from 1-(diphenylphosphino)-1'-ferrocenecarboxylic acid and studied as ligands for palladium. Starting with [PdCl2(cod)], the reactions at a 2 : 1 ligand-to-metal ratio gave uniformly the bis-phosphine complexes [PdCl2(L-kappaP)2] (3, L = 1; 4, L = 2) whereas those performed at a 1 : 1 ratio yielded distinct products: [PdCl2(1-kappa(2)P,N)] (5) with 1 coordinating as a trans-spanning P,N-donor, and the symmetric, P,N-bridged dimer [(micro-2-N,P)2{PdCl2}2] (6), respectively. The crystal structures of 1, 2, 4.4CHCl3, 5.AcOH, and 6.8CHCl3 as determined by X-ray diffraction showed the compounds to form well defined solid-state assemblies through hydrogen bonds. Testing of the phosphinocarboxamides in the palladium-catalysed Suzuki cross-coupling reaction revealed 1 and 2, combined with Pd(OAc)2 to form efficient catalysts for the reactions of aryl bromides while aryl chlorides coupled only when activated with electron-withdrawing groups.

Stereoselective Formation of Trisubstituted Vinyl Boronate Esters by the Acid-Mediated Elimination of α-Hydroxyboronate Esters

PubMed Central

2015-01-01

The copper-catalyzed diboration of ketones followed by an acid-catalyzed elimination leads to the formation of 1,1-disubstituted and trisubstituted vinyl boronate esters with moderate to good yields and selectivity. Addition of tosic acid to the crude diboration products provides the corresponding vinyl boronate esters upon elimination. The trisubstituted vinyl boronate esters are formed as the (Z)-olefin isomer, which was established by subjecting the products to a Suzuki–Miyaura coupling reaction to obtain alkenes of known geometry. PMID:24915498

Structure determination of a key intermediate of the enantioselective Pd complex catalyzed allylic substitution reaction

PubMed

Junker; Reif; Steinhagen; Junker; Felli; Reggelin; Griesinger

2000-09-01

The structure of a catalytic intermediate with important implications for the interpretation of the stereochemical outcome of the palladium complex catalyzed allylic substitution with phosphino-oxazoline (PHOX) ligands is determined by liquid state NMR. The complex displays a novel structure that is highly distorted compared with other palladium eta2-olefin complexes known so far. The structure has been determined from nuclear overhauser data (NOE), scalar coupling constants, and long range projection angle restraints derived from dipole dipole cross-correlated relaxation of multiple quantum coherence. The latter restraints have been implemented into a distance geometry protocol. The projection angle restraints yield a higher precision in the determination of the relative orientation of the two molecular moieties and are essential to provide an exact structural definition of the olefinic part of the catalytic intermediate with respect to the ligand.

Two Palladium-Catalyzed Domino Reactions from One Set of Substrates/Reagents: Efficient Synthesis of Substituted Indenes and cis-Stilbenoid Hydrocarbons from the Same Internal Alkynes and Hindered Grignard Reagents

PubMed Central

Dong, Cheng-Guo; Yeung, Pik; Hu, Qiao-Sheng

2008-01-01

Two types of domino reactions from the same internal alkynes and hindered Grignard reagents based on carbopalladation, Pd-catalyzed cross-coupling reaction and C-H activation strategy are described. The realization of these domino reactions relied on the control of the use of the ligand and the reaction temperature. Our study provides an efficient access to useful polysubstituted indenes and cis-substituted stilbenes, and may offer new means to the development of tandem/domino reactions in a more efficient way. PMID:17217305

Palladium-Catalyzed Dehydrogenative Coupling: An Efficient Synthetic Strategy for the Construction of the Quinoline Core

PubMed Central

Carral-Menoyo, Asier; Ortiz-de-Elguea, Verónica; Martinez-Nunes, Mikel; Sotomayor, Nuria; Lete, Esther

2017-01-01

Palladium-catalyzed dehydrogenative coupling is an efficient synthetic strategy for the construction of quinoline scaffolds, a privileged structure and prevalent motif in many natural and biologically active products, in particular in marine alkaloids. Thus, quinolines and 1,2-dihydroquinolines can be selectively obtained in moderate-to-good yields via intramolecular C–H alkenylation reactions, by choosing the reaction conditions. This methodology provides a direct method for the construction of this type of quinoline through an efficient and atom economical procedure, and constitutes significant advance over the existing procedures that require preactivated reaction partners. PMID:28867803

Synthesis and Structure of Fully Conjugated Block Copolymers Utilized in Organic Photovoltaics

NASA Astrophysics Data System (ADS)

Lee, Youngmin; Aplan, Melissa; Wang, Qing; Gomez, Enrique D.

2015-03-01

Fully conjugated block copolymers have the potential to overcome many of the limitations of mixtures and blends as photoactive layers in solar cells; furthermore, they may serve as model systems to study fundamental questions regarding optoelectric properties and charge transfer. However, the synthesis of fully conjugated block copolymers remains a challenging issue in the fieldchallenge. We have optimized the two-step synthesis of P3HT-b-PFTBT, which is composed comprised of Grignard metathesis for polymerization of P3HT followed by chain extension through a Suzuki-Miyaura polycondenstation. We find that the concentration of the Grignard reagent is critical for end-group control such that P3HT is terminated by H at one end and Br at the other. Furthermore, we can utilize an asymmetric feed ratio of monomers for the Suzuki-Miyaura reaction to minimize the amount of uncoupled homopolymers and to control the molecular weight of the second block. We investigated the chemical composition, structure and electrical characteristics of the polymers prepared by the different synthetic methods, and demonstrate that we can utilize these strategies for the synthesis of block copolymers beyond P3HT-b-PFTBT.

Pharmacomodulation of the Antimalarial Plasmodione: Synthesis of Biaryl- and N-Arylalkylamine Analogues, Antimalarial Activities and Physicochemical Properties.

PubMed

Urgin, Karène; Jida, Mouhamad; Ehrhardt, Katharina; Müller, Tobias; Lanzer, Michael; Maes, Louis; Elhabiri, Mourad; Davioud-Charvet, Elisabeth

2017-01-19

With the aim of increasing the structural diversity on the early antimalarial drug plasmodione, an efficient and versatile procedure to prepare a series of biaryl- and N -arylalkylamines as plasmodione analogues is described. Using the naturally occurring and commercially available menadione as starting material, a 2-step sequence using a Kochi-Anderson reaction and subsequent Pd-catalyzed Suzuki-Miyaura coupling was developed to prepare three representative biphenyl derivatives in good yields for antimalarial evaluation. In addition, synthetic methodologies to afford 3-benzylmenadione derivatives bearing a terminal - N (Me)₂ or - N (Et)₂ in different positions ( ortho , meta and para) on the aryl ring of the benzylic chain of plasmodione were investigated through reductive amination was used as the optimal route to prepare these protonable N -arylalkylamine privileged scaffolds. The antimalarial activities were evaluated and discussed in light of their physicochemical properties. Among the newly synthesized compounds, the para -position of the substituent remains the most favourable position on the benzyl chain and the carbamate - N HBoc was found active both in vitro (42 nM versus 29 nM for plasmodione) and in vivo in Plasmodium berghei -infected mice. The measured acido-basic features of these new molecules support the cytosol-food vacuole shuttling properties of non-protonable plasmodione derivatives essential for redox-cycling. These findings may be useful in antimalarial drug optimization.

Structural Analogues of Selfotel.

PubMed

Dziuganowska, Zofia A; Ślepokura, Katarzyna; Volle, Jean-Noël; Virieux, David; Pirat, Jean-Luc; Kafarski, Paweł

2016-06-17

A small library of phosphonopiperidylcarboxylic acids, analogues of NMDA antagonist selfotel (CGS 19755), was synthesized. First, the series of aromatic esters was obtained via a palladium-catalyzed cross-coupling reaction (Hirao coupling) of dialkyl phosphites with bromopyridinecarboxylates, followed by their hydrolysis. Then, hydrogenation of the resulting phosphonopyridylcarboxylic acids over PtO2 yielded the desired phosphonopiperidylcarboxylic acids. NMR studies indicated that the hydrogenation reaction proceeds predominantly by cis addition. Several compounds were obtained as monocrystal structures. Preliminary biological studies performed on cultures of neurons suggest that the obtained compounds possess promising activity toward NMDA receptors.

Modular in situ-Functionalization Strategy: Multicomponent Polymerization via Palladium/Norbornene Cooperative Catalysis.

PubMed

Yoon, Ki-Young; Dong, Guangbin

2018-05-23

Herein, we report the palladium/norbornene cooperatively catalyzed polymerization, which simplifies synthesis of functional aromatic polymers, including conjugated polymers. Specifically, an A2B2C-type multicomponent polymerization is developed using ortho-amination/ipso-alkynylation reaction for preparing various amine-functionalized arylacetylene-containing polymers. Within a single catalytic cycle, the amine side-chains are site-selectively installed in situ via C-H activation during the polymerization process, which represents a major difference from conventional cross-coupling polymerizations. This in situ-functionalization strategy enables modular incorporation of functional side-chains from simple monomers, thereby conveniently affording a diverse range of functional polymers. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

(E)-5-(Tributylstannylmethylidene)-5H-furan-2-ones: versatile synthons for the stereospecific elaboration of gamma-alkylidenebutenolide skeletons.

PubMed

Rousset, S; Abarbri, M; Thibonnet, J; Duchêne, A; Parrain, J L

1999-09-09

[reaction: see text] Stereoselective construction of (E)-gamma-tributylstannylmethylidene butenolides 1 was achieved through the palladium-catalyzed tandem cross-coupling/cyclization reactions of tributylstannyl 3-iodopropenoate derivatives with tributyltinacetylene. Iododestannylation of 1 occurs with inversion of the configuration of the exocyclic double bond while the observed selectivity in the Stille reaction was found to be dependent on the nature of the aryl halide.

Palladium-catalyzed Br/D exchange of arenes: Selective deuterium incorporation with versatile functional group tolerance and high efficiency

DOE PAGES

Zhang, Honghai -Hai; Bonnesen, Peter V.; Hong, Kunlun

2015-07-13

There is a facile method for introducing one or more deuterium atoms onto an aromatic nucleus via Br/D exchange with high functional group tolerance and high incorporation efficiency is disclosed. Deuterium-labeled aryl chlorides and aryl borates which could be used as substrates in cross-coupling reactions to construct more complicated deuterium-labeled compounds can also be synthesized by this method.

Synthesis of monodentate ferrocenylphosphines and their application to the palladium-catalyzed Suzuki reaction of aryl chlorides.

PubMed

Pickett, Tom E; Roca, Francesc X; Richards, Christopher J

2003-04-04

Racemic and enantiopure ((p)()S)-1-bromo-2-methylferrocene 6 were synthesized in 4 steps from 2-(4,4-dimethyloxazolinyl)ferrocene and (S)-2-(4-methylethyloxazolinyl)ferrocene, respectively (46 and 81% overall yield). Bromolithium exchange and addition of ClPR(2) gave the corresponding racemic or enantiopure 2-methylferrocenyl phosphine ligands 2-MeFcPR(2) 11 (R = Ph), 12 (R = Cy), and 13 (R = (t)Bu) in 28-93% yield. Use of PCl(3) gave the C(3)-symmetric phosphine (2-MeFc)(3)P 5 from ((p)()S)-6(72% yield) but racemic 6 did not lead to the formation of triferrocenyl phosphines. Combination of 5 and Pd(2)(dba)(3) gave an active catalyst for the Suzuki reaction of aryl chlorides, for example, 4-chlorotoluene and phenylboronic acid reacted at only 60 degrees C in dioxane (86% yield). Other examples are reported together with the use of 12 in this same protocol. From the X-ray crystal structure of 5 the cone angle was determined as 211 degrees. With this, and the electronic character of 11, 12, and other phosphines (derived from nu(CO) of trans-[(R(3)P)(2)Rh(CO)Cl]), an analysis is made of the steric and electronic influences on ligand activity in the Suzuki reaction.

Stereospecific nickel-catalyzed cross-coupling reactions of benzylic ethers and esters.

PubMed

Tollefson, Emily J; Hanna, Luke E; Jarvo, Elizabeth R

2015-08-18

This Account presents the development of a suite of stereospecific alkyl-alkyl cross-coupling reactions employing nickel catalysts. Our reactions complement related nickel-catalyzed stereoconvergent cross-coupling reactions from a stereochemical and mechanistic perspective. Most reactions of alkyl electrophiles with low-valent nickel complexes proceed through alkyl radicals and thus are stereoablative; the correct enantioselective catalyst can favor the formation of one enantiomer. Our reactions, in contrast, are stereospecific. Enantioenriched ethers and esters are cleanly converted to cross-coupled products with high stereochemical fidelity. While mechanistic details are still to be refined, our results are consistent with a polar, two-electron oxidative addition that avoids the formation of radical intermediates. This reactivity is unusual for a first-row transition metal. The cross-coupling reactions engage a range of benzylic ethers and esters, including methyl ethers, tetrahydropyrans, tetrahydrofurans, esters, and lactones. Coordination of the arene substituent to the nickel catalyst accelerates the reactions. Arenes with low aromatic stabilization energies, such as naphthalene, benzothiophene, and furan, serve as the best ligands and provide the highest reactivity. Traceless directing groups that accelerate reactions of sluggish substrates are described, providing partial compensation for arene coordination. Kumada, Negishi, and Suzuki reactions provide incorporation of a broad range of transmetalating agents. In Kumada coupling reactions, a full complement of Grigard reagents, including methyl, n-alkyl, and aryl Grignard reagents, are employed. In reactions employing methylmagnesium iodide, ligation of the nickel catalyst by rac-BINAP or DPEphos provides the highest yield and stereospecificity. For all other Grignard reagents, Ni(dppe)Cl2 has emerged as the best catalyst. Negishi cross-coupling reactions employing dimethylzinc are reported as a strategy to increase the functional group tolerance of the reaction. We also describe Suzuki reactions using arylboronic esters. These reactions provided the first example in the series of a switch in stereochemical outcome. The reactions maintain stereospecificity, but reactions employing different achiral ligands provide opposite enantiomers of the product. Use of an N-heterocyclic carbene ligand, SIMes, provides inversion, consistent with our prior work in Kumada and Negishi coupling reactions. Use of the electron-rich phosphine PCy3, however, provides retention with stereospecificity, signaling a change in the mechanistic details. Potential applications of the reported cross-coupling reactions include the synthesis of medicinal agents containing the 2-arylalkane and 1,1-diarylalkane moieties, which are pharmacophores in medicinal chemistry. These moieties are found in compounds with activity against a broad range of indications, including cancer, heart disease, diabetes, osteoporosis, smallpox, tuberculosis, and insomnia. We highlight representative examples of bioactive compounds that we have prepared with high enantioselectivity employing our methods, as well as the discovery of a new anti-cancer agent.

Intramolecular Charge-Transfer Interaction of Donor-Acceptor-Donor Arrays Based on Anthracene Bisimide.

PubMed

Iwanaga, Tetsuo; Ogawa, Marina; Yamauchi, Tomokazu; Toyota, Shinji

2016-05-20

We designed anthracene bisimide (ABI) derivatives having two triphenylamine (TPA) groups as donor units at the 9,10-positions to form a novel π-conjugated donor-acceptor system. These compounds and their analogues with ethynylene linkers were synthesized by Suzuki-Miyaura and Sonogashira coupling reactions, respectively. In UV-vis spectra, the linker-free derivatives showed broad absorption bands arising from intramolecular charge-transfer interactions. Introducing ethynylene linkers resulted in a considerable red shift of the absorption bands. In fluorescence spectra, the ethynylene derivatives showed intense emission bands at 600-650 nm. Their photophysical and electrochemical properties were compared with those of the corresponding mono TPA derivatives on the basis of theoretical calculations and cyclic voltammetry to evaluate the intramolecular electronic interactions between the donor and acceptor units.

Two palladium-catalyzed domino reactions from one set of substrates/reagents: efficient synthesis of substituted indenes and cis-stilbenoid hydrocarbons from the same internal alkynes and hindered Grignard reagents.

PubMed

Dong, Cheng-Guo; Yeung, Pik; Hu, Qiao-Sheng

2007-01-18

Two types of domino reactions from the same internal alkynes and hindered Grignard reagents based on carbopalladation, Pd-catalyzed cross-coupling reaction, and a C-H activation strategy are described. The realization of these domino reactions relied on the control of the use of the ligand and the reaction temperature. Our study provides efficient access to useful polysubstituted indenes and cis-substituted stilbenes and may offer a new means of development of tandem/domino reactions in a more efficient way. [reaction: see text].

Suzuki–Miyaura Cross-Coupling of Aryl Carbamates and Sulfamates: Experimental and Computational Studies

PubMed Central

Quasdorf, Kyle W.; Antoft-Finch, Aurora; Liu, Peng; Silberstein, Amanda L.; Komaromi, Anna; Blackburn, Tom; Ramgren, Stephen D.; Houk, K. N.; Snieckus, Victor; Garg, Neil K.

2011-01-01

The first Suzuki–Miyaura cross-coupling reactions of the synthetically versatile O-aryl carbamate and O-sulfamate groups is described. The transformations utilize the inexpensive, bench-stable catalyst NiCl2(PCy3)2 to furnish biaryls in good to excellent yields. A broad scope for this methodology has been demonstrated. Substrates with electron-donating and electron-withdrawing groups (EDGs, EWGs) are tolerated, in addition to those that possess ortho substitutents. Furthermore, heteroaryl substrates may be employed as coupling partners. A computational study providing the full catalytic cycles for these cross-coupling reactions is described. The oxidative additions with carbamates and sulfamates occur via a five-centered transition state, resulting in the exclusive cleavage of the Ar–O bond. Water is found to stabilize the Ni–carbamate catalyst resting state, and thus provides rationalization of the relative decreased rate of coupling of carbamates. Several synthetic applications are presented to showcase the utility of the methodology in the synthesis of polysubstituted aromatic compounds of natural product and bioactive molecule interest. PMID:21456551

Palladium-Catalyzed Nitromethylation of Aryl Halides: An Orthogonal Formylation Equivalent

PubMed Central

Walvoord, Ryan R.; Berritt, Simon; Kozlowski, Marisa C.

2012-01-01

An efficient cross-coupling reaction of aryl halides and nitromethane was developed with the use of parallel microscale experimentation. The arylnitromethane products are precursors for numerous useful synthetic products. An efficient method for their direct conversion to the corresponding oximes and aldehydes in a one-pot operation has been discovered. The process exploits inexpensive nitromethane as a carbonyl equivalent, providing a mild and convenient formylation method that is compatible with many functional groups. PMID:22839593

Palladium-mediated strategies for functionalizing the dihydroazulene photoswitch: paving the way for its exploitation in molecular electronics.

PubMed

Jevric, Martyn; Broman, Søren Lindbæk; Nielsen, Mogens Brøndsted

2013-05-03

The dihydroazulene (DHA)/vinylheptafulvene (VHF) photo/thermoswitch has attracted interest as a molecular switch for advanced materials and molecular electronics. We report here two synthetic approaches using palladium catalysis for synthesizing dihydroazulene (DHA) photoswitches with thioacetate anchoring groups intended for molecular electronics applications. The first methodology involves a Suzuki coupling using tert-butyl thioether protecting groups. Conversion to the thioacetate using boron tribromide/acetyl chloride results in the formation of the product as a mixture of regioisomers mediated by a ring-opening reaction. The second approach circumvents isomerization by the synthesis of stannanes as intermediates and their use in a Stille coupling. Although fully unsaturated azulenes are formed as byproducts during the synthesis of the DHA stannanes, this approach allowed the regioselective incorporation of the thioacetate anchoring group in either one of the two ends (positions 2 or 7) or at both.

Construction of new biopolymer (chitosan)-based pincer-type Pd(II) complex and its catalytic application in Suzuki cross coupling reactions

NASA Astrophysics Data System (ADS)

Baran, Talat; Menteş, Ayfer

2017-04-01

In this paper we described the fabrication, characterization and application of a new biopolymer (chitosan)-based pincer-type Pd(II) catalyst in Suzuki cross coupling reactions using a non-toxic, cheap, eco-friendly and practical method. The catalytic activity tests showed remarkable product yields as well as TON (19800) and TOF (330000) values with a small catalyst loading. In addition, the catalyst indicated good recyclability in the Suzuki C-C reaction. This biopolymer supported catalyst can be used with various catalyst systems due to its unique properties, such as being inert, green in nature, low cost and chemically durable.

Synthesis, characterization, and reactivity of arylpalladium cyanoalkyl complexes: selection of catalysts for the alpha-arylation of nitriles.

PubMed

Culkin, Darcy A; Hartwig, John F

2002-08-14

A new coupling process, the palladium-catalyzed alpha-arylation of nitriles, was developed by exploring the structure and reactivity of arylpalladium cyanoalkyl complexes. Complexes of 1,2-bis(diphenylphosphino)benzene (DPPBz), 1,1'-bis(di-i-propylphosphino)ferrocene (D(i)()PrPF), racemic-2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (BINAP), and diphenylethylphosphine (PPh(2)Et) were prepared. Coordination to palladium through the alpha-carbon was observed for DPPBz-ligated complexes and for complexes of primary and benzylic nitrile anions. However, the anion of isobutyronitrile was coordinated to palladium through the cyano-nitrogen when the complex was ligated by D(i)()PrPF. The isobutyronitrile anion displaced a phosphine ligand to form a C,N-bridged dimer when generated from PPh(2)Et-ligated palladium. These results suggest that the nitrile anion preferentially coordinates to palladium through the carbon atom in the absence of steric effects. Thermolysis of the arylpalladium cyanoalkyl complexes led to reductive elimination that formed alpha-aryl nitriles. The high yields and short reaction times observed for BINAP-ligated complexes suggested that BINAP-ligated palladium catalysts might be appropriate for the arylation of nitriles. Initial results on a palladium-catalyzed process for the direct coupling of aryl bromides and primary, benzylic, and secondary nitrile anions to form alpha-aryl nitriles in good yields are reported.

Synthesis of a Tyr-Tyr Dipeptide Library and Evaluation Against Tumor Cells.

PubMed

Vasconcelos, Stanley Ns; Sciani, Juliana M; Lisboa, Nicole Mambeli; Stefani, Helio A

2018-03-09

Structural component of proteins and peptides, amino acids have been used as building blocks in the synthesis of more complex molecules with antitumor activity against several types of cancer. The search for new anticancer compounds is ongoing, especially for cancers that are very aggressive and have poor prognoses, such as leukemia. Here, we report a method to synthesize Tyr-Tyr dipeptides via sonochemistry reactions followed by functionalization of these Tyr-Tyr dipeptides with Suzuki-Miyaura and Sonogashira cross-coupling reactions in good yields. Twelve different Tyr-Tyr dipeptides were investigated against three cell lines: HaCaT; Jurkat-E6; and A2058. Some of Tyr-Tyr dipeptides showed activity against Jurkat-E6 leukaemia cells at low concentration, decreasing their viability, but not against non-tumor HaCaT cells, suggesting a cytotoxicity specific to tumor cells. All dipeptides were able to decrease the viability of Jurkat cell line, however the A2058 cell line did not respond well to treatment with the peptides. Some of the modified Tyr-Tyr dipeptides presented selective activity on leukemic tumor cells. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

The synthesis and luminescence of europium (III) complex based on deprotonated 1-(4-ethyl-4H-thieno[3,2-b]indol-6-yl)-4,4,4-trifluorobutane-1,3-dionate and 1,10-phenanthroline

NASA Astrophysics Data System (ADS)

Liu, Sheng-Gui; Su, Wen-Yi; Pan, Rong-Kai; Zhou, Xiao-Ping; Wen, Xin-Lan; Chen, Yi-Zhao; Wang, Sheng; Shi, Xiao-Bo

2013-02-01

A new β-diketone ligand, 1-(4-ethyl-4H-thieno[3,2-b]indol-6-yl)-4,4,4-trifluoro-butane-1,3-dione(HL) was synthesized by four steps reaction (Suzuki-Miyaura cross-coupling, Cadogan cyclization, N-ethylation and Claisen condensation reaction) from 1-(4-bromo-3-nitrophenyl)ethanone and thiophen-2-ylboronic acid. Deprotonated ligand (L-1) and 1,10-phenanthroline (phen) coordinated to Eu3+ to obtain a new europium (III) complex, EuL3(phen). The complex was characterized by elementary analysis, IR, 1H NMR, UV-Visible absorption spectroscopy, thermogravimetric analysis (TGA) and photoluminescence (PL) measurements in detail. TGA shows that the decomposition temperature of the complex is up to 320 °C. PL measurement results indicate that the Eu(III) complex exhibit intense red-emission with the characteristic of europium ion. Red LED device was successfully fabricated by employing the complex onto 380 nm-emitting InGaN chip, which shows that the complex can act as red phosphor in combination with 380 nm-emitting chips.

Minimizing the amount of nitromethane in palladium-catalyzed cross-coupling with aryl halides.

PubMed

Walvoord, Ryan R; Kozlowski, Marisa C

2013-09-06

A method for the formation of arylnitromethanes is described that employs readily available aryl halides or triflates and small amounts of nitromethane in a dioxane solvent, thereby reducing the hazards associated with this reagent. Specifically, 2-10 equiv (1-5% v/v) of nitromethane can be employed in comparison to prior work that used nitromethane as solvent (185 equiv). The present transformation provides high yields at relatively low temperatures and tolerates an array of functionality, including heterocycles and substantial steric encumbrance.

Copper-free Sonogashira cross-coupling for functionalization of alkyne-encoded proteins in aqueous medium and in bacterial cells.

PubMed

Li, Nan; Lim, Reyna K V; Edwardraja, Selvakumar; Lin, Qing

2011-10-05

Bioorthogonal reactions suitable for functionalization of genetically or metabolically encoded alkynes, for example, copper-catalyzed azide-alkyne cycloaddition reaction ("click chemistry"), have provided chemical tools to study biomolecular dynamics and function in living systems. Despite its prominence in organic synthesis, copper-free Sonogashira cross-coupling reaction suitable for biological applications has not been reported. In this work, we report the discovery of a robust aminopyrimidine-palladium(II) complex for copper-free Sonogashira cross-coupling that enables selective functionalization of a homopropargylglycine (HPG)-encoded ubiquitin protein in aqueous medium. A wide range of aromatic groups including fluorophores and fluorinated aromatic compounds can be readily introduced into the HPG-containing ubiquitin under mild conditions with good to excellent yields. The suitability of this reaction for functionalization of HPG-encoded ubiquitin in Escherichia coli was also demonstrated. The high efficiency of this new catalytic system should greatly enhance the utility of Sonogashira cross-coupling in bioorthogonal chemistry.

Palladium Nanoparticles Immobilized on Individual Calcium Carbonate Plates Derived from Mussel Shell Waste: An Ecofriendly Catalyst for the Copper-Free Sonogashira Coupling Reaction.

PubMed

Saetan, Trin; Lertvachirapaiboon, Chutiparn; Ekgasit, Sanong; Sukwattanasinitt, Mongkol; Wacharasindhu, Sumrit

2017-09-05

The conversion of waste into high-value materials is considered an important sustainability strategy in modern chemical industries. A large volume of shell waste is generated globally from mussel cultivation. In this work, mussel shell waste (Perna viridis) is transformed into individual calcium carbonate plates (ICCPs) and is applied as a support for a heterogeneous catalyst. Palladium nanoparticles (3-6 nm) are deposited with an even dispersion on the ICCP surface, as demonstrated by X-ray diffraction and scanning electron microscopy. Using this system, Sonogashira cross-coupling reactions between aryl iodides and terminal acetylenes were accomplished in high yields with the use of 1 % Pd/ICCP in the presence of potassium carbonate without the use of any copper metal or external ligand. The Pd/ICCP catalyst could also be reused up to three times and activity over 90 % was maintained with negligible Pd-metal leaching. This work demonstrates that mussel shell waste can be used as an inexpensive and effective support for metal catalysts in coupling reactions, as demonstrated by the successful performance of the Pd-catalyzed, copper-free Sonogashira cross-coupling process. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Nitrous Oxide-dependent Iron-catalyzed Coupling Reactions of Grignard Reagents.

PubMed

Döhlert, Peter; Weidauer, Maik; Enthaler, Stephan

2015-01-01

The formation of carbon-carbon bonds is one of the fundamental transformations in chemistry. In this regard the application of palladium-based catalysts has been extensively investigated during recent years, but nowadays research focuses on iron catalysis, due to sustainability, costs and toxicity issues; hence numerous examples for iron-catalyzed cross-coupling reactions have been established, based on the coupling of electrophiles (R(1)-X, X = halide) with nucleophiles (R(2)-MgX). Only a small number of protocols deals with the iron-catalyzed oxidative coupling of nucleophiles (R(1)-MgX + R(2)-MgX) with the aid of oxidants (1,2-dihaloethanes). However, some issues arise with these oxidants; hence more recently the potential of the industrial waste product nitrous oxide (N(2)O) was investigated, because the unproblematic side product N(2) is formed. Based on that, we demonstrate the catalytic potential of easily accessible iron complexes in the oxidative coupling of Grignard reagents. Importantly, nitrous oxide was essential to obtain yields up to >99% at mild conditions (e.g. 1 atm, ambient temperature) and low catalyst loadings (0.1 mol%) Excellent catalyst performance is realized with turnover numbers of up to 1000 and turnover frequencies of up to 12000 h(-1). Moreover, a good functional group tolerance is observed (e.g. amide, ester, nitrile, alkene, alkyne). Afterwards the reaction of different Grignard reagents revealed interesting results with respect to the selectivity of cross-coupling product formation.

Palladium-Copper Catalyzed Alkyne Activation as an Entry to Multicomponent Syntheses of Heterocycles

NASA Astrophysics Data System (ADS)

Müller, Thomas J. J.

Alkynones and chalcones are of paramount importance in heterocyclic chemistry as three-carbon building blocks. In a very efficient manner, they can be easily generated by palladium-copper catalyzed reactions: ynones are formed from acid chlorides and terminal alkynes, and chalcones are synthesized in the sense of a coupling-isomerization (CI) sequence from (hetero)aryl halides and propargyl alcohols. Mild reaction conditions now open entries to sequential and consecutive transformations to heterocycles, such as furans, 3-halo furans, pyrroles, pyrazoles, substituted and annelated pyridines, annelated thiopyranones, pyridimines, meridianins, benzoheteroazepines and tetrahydro-β-carbolines, by consecutive coupling-cyclocondensation or CI-cyclocondensation sequences, as new diversity oriented routes to heterocycles. Domino reactions based upon the coupling-isomerization reaction (CIR) have been probed in the synthesis of antiparasital 2-substituted quinoline derivatives and highly luminescent spiro-benzofuranones and spiro-indolones.

Nickel-Catalyzed Coupling Reactions of Alkyl Electrophiles, Including Unactivated Tertiary Halides, to Generate Carbon–Boron Bonds

PubMed Central

Dudnik, Alexander S.

2012-01-01

Through the use of a catalyst formed in situ from NiBr2•diglyme and a pybox ligand (both of which are commercially available), we have achieved our first examples of coupling reactions of unactivated tertiary alkyl electrophiles, as well as our first success with nickel-catalyzed couplings that generate bonds other than C–C bonds. Specifically, we have determined that this catalyst accomplishes Miyaura-type borylations of unactivated tertiary, secondary, and primary alkyl halides with diboron reagents to furnish alkylboronates, a family of compounds with substantial (and expanding) utility, under mild conditions; indeed, the umpolung borylation of a tertiary alkyl bromide can be achieved at a temperature as low as −10 °C. The method exhibits good functional-group compatibility and is regiospecific, both of which can be issues with traditional approaches to the synthesis of alkylboronates. In contrast to seemingly related nickel-catalyzed C–C bond-forming processes, tertiary halides are more reactive than secondary or primary halides in this nickel-catalyzed C–B bond-forming reaction; this divergence is particularly noteworthy in view of the likelihood that both transformations follow an inner-sphere electron-transfer pathway for oxidative addition. PMID:22668072

Rapid Synthesis of Thiophene-Based, Organic Dyes for Dye-Sensitized Solar Cells (DSSCs) by a One-Pot, Four-Component Coupling Approach.

PubMed

Matsumura, Keisuke; Yoshizaki, Soichi; Maitani, Masato M; Wada, Yuji; Ogomi, Yuhei; Hayase, Shuzi; Kaiho, Tatsuo; Fuse, Shinichiro; Tanaka, Hiroshi; Takahashi, Takashi

2015-06-26

This one-pot, four-component coupling approach (Suzuki-Miyaura coupling/C-H direct arylation/Knoevenagel condensation) was developed for the rapid synthesis of thiophene-based organic dyes for dye-sensitized solar cells (DSSCs). Seven thiophene-based, organic dyes of various donor structures with/without the use of a 3,4-ethylenedioxythiophene (EDOT) moiety were successfully synthesized in good yields based on a readily available thiophene boronic acid pinacol ester scaffold (one-pot, 3-step, 35-61%). Evaluation of the photovoltaic properties of the solar cells that were prepared using the synthesized dyes revealed that the introduction of an EDOT structure beside a cyanoacrylic acid moiety improved the short-circuit current (Jsc) while decreasing the fill factor (FF). The donor structure significantly influenced the open-circuit voltage (Voc), the FF, and the power conversion efficiency (PCE). The use of a n-hexyloxyphenyl amine donor, and our originally developed, rigid, and nonplanar donor, both promoted good cell performance (η=5.2-5.6%). © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Rhodium-catalyzed C-H bond activation for the synthesis of quinonoid compounds: Significant Anti-Trypanosoma cruzi activities and electrochemical studies of functionalized quinones.

PubMed

Jardim, Guilherme A M; Silva, Thaissa L; Goulart, Marilia O F; de Simone, Carlos A; Barbosa, Juliana M C; Salomão, Kelly; de Castro, Solange L; Bower, John F; da Silva Júnior, Eufrânio N

2017-08-18

Thirty four halogen and selenium-containing quinones, synthesized by rhodium-catalyzed C-H bond activation and palladium-catalyzed cross-coupling reactions, were evaluated against bloodstream trypomastigotes of T. cruzi. We have identified fifteen compounds with IC 50 /24 h values of less than 2 μM. Electrochemical studies on A-ring functionalized naphthoquinones were also performed aiming to correlate redox properties with trypanocidal activity. For instance, (E)-5-styryl-1,4-naphthoquinone 59 and 5,8-diiodo-1,4-naphthoquinone 3, which are around fifty fold more active than the standard drug benznidazole, are potential derivatives for further investigation. These compounds represent powerful new agents useful in Chagas disease therapy. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Incorporating perylene moiety into poly(phenothiazine-co-bithiophene) backbone for higher charge transport.

PubMed

Tang, Weihua; Ke, Lin; Chen, Zhi-Kuan

2008-03-27

Low band gap pi-conjugated polymers composed of phenothiazine, bithiophene, and perylene moieties were prepared in high yields by using a palladium-catalyzed Suzuki coupling reaction. The polymers were characterized by NMR, gel permeation chromatography, and elemental analysis. The characterizations revealed that high-molecular weight (weight-average molecular weight up to 42,400 g/mol) polymers were thermally stable with a decomposition temperature in the region of 338-354 degrees C and their glass transition temperatures (Tg) ranging from 124 to 136 degrees C. All polymers demonstrated broad optical absorption in the region of 300-550 nm with efficient blue-green light emission. The absorption was broadened further (for ca. 50 nm) when the perylene moiety was incorporated. Cyclic voltammograms displayed that the p- and n-doping processes of all the polymers were partially reversible and that electrochemical band gaps were as low as -2.30 eV with the incorporation of a perylene moiety. The hole mobility of polymers was evaluated by using the space-charge-limited current model with a device structure of ITO/PEDOT:PSS/polymer/Ca. The results show that the incorporation of perylene is beneficial for improving the hole mobility of the conjugated polymers.

Kinetic and spectroscopic studies of the [palladium(Ar-bian)]-catalyzed semi-hydrogenation of 4-octyne.

PubMed

Kluwer, Alexander M; Koblenz, Tehila S; Jonischkeit, Thorsten; Woelk, Klaus; Elsevier, Cornelis J

2005-11-09

The kinetics of the stereoselective semi-hydrogenation of 4-octyne in THF by the highly active catalyst [Pd{(m,m'-(CF(3))(2)C(6)H(3))-bian}(ma)] (2) (bian = bis(imino)acenaphthene; ma = maleic anhydride) has been investigated. The rate law under hydrogen-rich conditions is described by r = k[4-octyne](0.65)[Pd][H(2)], showing first order in palladium and dihydrogen and a broken order in substrate. Parahydrogen studies have shown that a pairwise transfer of hydrogen atoms occurs in the rate-limiting step. In agreement with recent theoretical results, the proposed mechanism consists of the consecutive steps: alkyne coordination, heterolytic dihydrogen activation (hydrogenolysis of one Pd-N bond), subsequent hydro-palladation of the alkyne, followed by addition of N-H to palladium, reductive coupling of vinyl and hydride and, finally, substitution of the product alkene by the alkyne substrate. Under hydrogen-limiting conditions, side reactions occur, that is, formation of catalytically inactive palladacycles by oxidative alkyne coupling. Furthermore, it has been shown that (Z)-oct-4-ene is the primary reaction product, from which the minor product (E)-oct-4-ene is formed by an H(2)-assisted, palladium-catalyzed isomerization reaction.

Minimizing the Amount of Nitromethane in Palladium Catalyzed Cross Coupling with Aryl Halides

PubMed Central

Walvoord, Ryan R.; Kozlowski, Marisa C.

2013-01-01

A method for the formation of arylnitromethanes is described that employs readily available aryl halides or triflates and small amounts of nitromethane in a dioxane solvent, thereby reducing the hazards associated with this reagent. Specifically, 2–10 equivalents (1–5% v/v) of nitromethane can be employed in comparison to prior work that used nitromethane as solvent (185 equivalents). The present transformation provides high yields at relatively low temperatures and tolerates an array of functionality, including heterocycles and substantial steric encumbrance. PMID:23895411

Stereoconvergent Amine-Directed Alkyl–Alkyl Suzuki Reactions of Unactivated Secondary Alkyl Chlorides

PubMed Central

Lu, Zhe; Wilsily, Ashraf; Fu, Gregory C.

2011-01-01

A new family of stereoconvergent cross-couplings of unactivated secondary alkyl electrophiles has been developed, specifically, arylamine-directed alkyl–alkyl Suzuki reactions. This represents the first such investigation to be focused on the use of alkyl chlorides as substrates. Structure-enantioselectivity studies are consistent with the nitrogen, not the aromatic ring, serving as the primary site of coordination of the arylamine to the catalyst. The rate law for this asymmetric cross-coupling is compatible with transmetalation being the turnover-limiting step of the catalytic cycle. PMID:21553917

Recent advances in heterobimetallic palladium(II)/copper(II) catalyzed domino difunctionalization of carbon-carbon multiple bonds.

PubMed

Beccalli, Egle M; Broggini, Gianluigi; Gazzola, Silvia; Mazza, Alberto

2014-09-21

The double functionalization of carbon-carbon multiple bonds in one-pot processes has emerged in recent years as a fruitful tool for the rapid synthesis of complex molecular scaffolds. This review covers the advances in domino reactions promoted by the couple palladium(ii)/copper(ii), which was proven to be an excellent catalytic system for the functionalization of substrates.

Palladium catalyzed hydrogenation of bio-oils and organic compounds

DOEpatents

Elliott, Douglas C [Kennewick, WA; Hu, Jianli [Richland, WA; Hart,; Todd, R [Kennewick, WA; Neuenschwander, Gary G [Burbank, WA

2011-06-07

The invention provides palladium-catalyzed hydrogenations of bio-oils and certain organic compounds. Experimental results have shown unexpected and superior results for palladium-catalyzed hydrogenations of organic compounds typically found in bio-oils.

Palladium catalyzed hydrogenation of bio-oils and organic compounds

DOEpatents

Elliott, Douglas C [Richland, WA; Hu, Jianli [Kennewick, WA; Hart, Todd R [Kennewick, WA; Neuenschwander, Gary G [Burbank, WA

2008-09-16

The invention provides palladium-catalyzed hydrogenations of bio-oils and certain organic compounds. Experimental results have shown unexpected and superior results for palladium-catalyzed hydrogenations of organic compounds typically found in bio-oils.

Development of a second generation palladium-catalyzed cycloalkenylation and its application to bioactive natural product synthesis.

PubMed

Toyota, Masahiro

2013-07-01

A novel palladium-catalyzed intramolecular oxidative alkylation of unactivated olefins is described. This protocol was devised to solve one of the drawbacks of the original palladium-catalyzed cycloalkenylation that we developed. We call this new procedure the 'second generation palladium-catalyzed cycloalkenylation'. This protocol has been applied to the total syntheses of cis-195A, trans-195A, boonein, scholareins A, C, D, and alpha-skytanthine.

Ambient Temperature Synthesis of High Enantiopurity N-Protected Peptidyl Ketones by Peptidyl Thiol Ester–Boronic Acid Cross-Coupling

PubMed Central

Yang, Hao; Li, Hao; Wittenberg, Rüdiger; Egi, Masahiro; Huang, Wenwei; Liebeskind, Lanny S.

2009-01-01

α-Amino acid thiol esters derived from N-protected mono-, di-, and tripeptides couple with aryl, π-electron-rich heteroaryl, or alkenyl boronic acids in the presence of stoichiometric Cu(I) thiophene-2-carboxylate (CuTC) and catalytic Pd2(dba)3/triethylphosphite to generate the corresponding N-protected peptidyl ketones in good to excellent yields and in high enantiopurity. Triethylphosphite plays a key role as a supporting ligand by mitigating an undesired palladium-catalyzed decarbonylation-β-elimination of the α-amino thiol esters. The peptidyl ketone synthesis proceeds at room temperature under non-basic conditions and demonstrates a high tolerance to functionality. PMID:17263394

Development of α-glucosidase inhibitors by room temperature C-C cross couplings of quinazolinones.

PubMed

Garlapati, Ramesh; Pottabathini, Narender; Gurram, Venkateshwarlu; Kasani, Kumara Swamy; Gundla, Rambabu; Thulluri, Chiranjeevi; Machiraju, Pavan Kumar; Chaudhary, Avinash B; Addepally, Uma; Dayam, Raveendra; Chunduri, Venkata Rao; Patro, Balaram

2013-08-07

Novel quinazolinone based α-glucosidase inhibitors have been developed. For this purpose a virtual screening model has been generated and validated utilizing acarbose as a α-glucosidase inhibitor. Homology modeling, docking, and virtual screening were successfully employed to discover a set of structurally diverse compounds active against α-glucosidase. A search of a 3D database containing 22,500 small molecules using the structure based virtual model yielded ten possible candidates. All ten candidates were N-3-pyridyl-2-cyclopropyl quinazolinone-4-one derivatives, varying at the 6 position. This position was modified by Suzuki-Miyaura cross coupling with aryl, heteroaryl, and alkyl boronic acids. A catalyst screen was performed, and using the best optimal conditions, a series of twenty five compounds was synthesized. Notably, the C-C cross coupling reactions of the 6-bromo-2-cyclopropyl-3-(pyridyl-3-ylmethyl)quinazolin-4(3H)-one precursor have been accomplished at room temperature. A comparison of the relative reactivities of 6-bromo and 6-chloro-2,3-disubstituted quinazolinones with phenyl boronic acid was conducted. An investigation of pre-catalyst loading for the reaction of the 6-bromo-2-cyclopropyl-3-(pyridyl-3-ylmethyl)quinazolin-4(3H)-one substrate was also carried out. Finally, we submitted our compounds to biological assays against α-glucosidase inhibitors. Of these, three hits (compounds 4a, 4t and 4r) were potentially active as α-glucosidase inhibitors and showed activity with IC50 values <20 μM. Based on structural novelty and desirable drug-like properties, 4a was selected for structure-activity relationship study, and thirteen analogs were synthesized. Nine out of thirteen analogs acted as α-glucosidase inhibitors with IC50 values <10 μM. These lead compounds have desirable physicochemical properties and are excellent candidates for further optimization.

Automated Synthesis of a 184-Member Library of Thiadiazepan-1, 1-dioxide-4-ones

PubMed Central

Fenster, Erik; Long, Toby R.; Zang, Qin; Hill, David; Neuenswander, Benjamin; Lushington, Gerald H.; Zhou, Aihua; Santini, Conrad; Hanson, Paul R.

2011-01-01

The construction of a 225-member (3 × 5 × 15) library of thiadiazepan-1,1-dioxide-4-ones was performed on a Chemspeed Accelerator (SLT-100) automated parallel synthesis platform, culminating in the successful preparation of 184/225 sultams. Three sultam core scaffolds were prepared based upon the utilization of an aza-Michael reaction on a multifunctional vinyl sulfonamide linchpin. The library exploits peripheral diversity in the form of a sequential, two-step [3 + 2] Huisgen cycloaddition/Pd-catalyzed Suzuki–Miyaura coupling sequence. PMID:21309582

Laccases as palladium oxidases.

PubMed

Mekmouche, Yasmina; Schneider, Ludovic; Rousselot-Pailley, Pierre; Faure, Bruno; Simaan, A Jalila; Bochot, Constance; Réglier, Marius; Tron, Thierry

2015-02-01

The first example of a coupled catalytic system involving an enzyme and a palladium(ii) catalyst competent for the aerobic oxidation of alcohol in mild conditions is described. In the absence of dioxygen, the fungal laccase LAC3 is reduced by a palladium(0) species as evidenced by the UV/VIS and ESR spectra of the enzyme. During the oxidation of veratryl alcohol performed in water, at room temperature and atmospheric pressure, LAC3 regenerates the palladium catalyst, is reduced and catalyzes the four-electron reduction of dioxygen into water with no loss of enzyme activity. The association of a laccase with a water-soluble palladium complex results in a 7-fold increase in the catalytic efficiency of the complex. This is the first step in the design of a family of renewable palladium catalysts for aerobic oxidation.

The Mechanochemical Reaction of Palladium(II) Chloride with a Bidentate Phosphine

ERIC Educational Resources Information Center

Berry, David E.; Carrie, Philippa; Fawkes, Kelli L.; Rebner, Bruce; Xing, Yao

2010-01-01

This experiment describes the reaction of palladium(II) chloride with 1,5-bis(diphenylphosphino)pentane by grinding the two powders together in the solid state. The product is the precursor for the metalation reaction at one of the methylene carbon atoms of the ligand's backbone. The final product is known to be a catalyst for Suzuki-Miyaura…

Potent and selective inhibitors of 11β-hydroxysteroid dehydrogenase type 1 labeled with carbon-13 and carbon-14.

PubMed

Latli, Bachir; Hrapchak, Matt; Savoie, Jolaine; Zhan, Yongda; Busacca, Carl A; Senanayake, Chris H

2017-07-01

(S)-6-(2-Hydroxy-2-methylpropyl)-3-((S)-1-(4-(1-methyl-2-oxo-1,2-dihydropyridin-4-yl)phenyl)ethyl)-6-phenyl-1,3-oxazinan-2-one (1) and (4aR,9aS)-1-(1H-benzo[d]midazole-5-carbonyl)-2,3,4,4a,9,9a-hexahydro-1-H-indeno[2,1-b]pyridine-6-carbonitrile hydrochloride (2) are potent and selective inhibitor of 11β-hydroxysteroid dehydrogenase type 1 enzyme. These 2 drug candidates developed for the treatment of type-2 diabetes were prepared labeled with carbon-13 and carbon-14 to enable drug metabolism, pharmacokinetics, bioanalytical, and other studies. In the carbon-13 synthesis, benzoic- 13 C 6 acid was converted in 7 steps and in 16% overall yield to [ 13 C 6 ]-(1). Aniline- 13 C 6 was converted in 7 steps to 1H-benzimidazole-1-2,3,4,5,6- 13 C 6 -5-carboxylic acid and then coupled to a tricyclic chiral indenopiperidine to afford [ 13 C 6 ]-(2) in 19% overall yield. The carbon-14 labeled (1) was prepared efficiently in 2 radioactive steps in 41% overall yield from an advanced intermediate using carbon-14 labeled methyl magnesium iodide and Suzuki-Miyaura cross coupling via in situ boronate formation. As for the synthesis of [ 14 C]-(2), 1H-benzimidazole-5-carboxylic- 14 C acid was first prepared in 4 steps using potassium cyanide- 14 C, then coupled to the chiral indenopiperidine using amide bond formation conditions in 26% overall yield. Copyright © 2017 John Wiley & Sons, Ltd.

Switching on Elusive Organometallic Mechanisms with Photoredox Catalysis

PubMed Central

Terrett, Jack A.; Cuthbertson, James D.; Shurtleff, Valerie W.; MacMillan, David W. C.

2015-01-01

Transition metal-catalyzed cross-coupling reactions have become one of the most utilized carbon–carbon and carbon–heteroatom bond-forming reactions in chemical synthesis. More recently, nickel catalysis has been shown to participate in a wide variety of C–C bond forming reactions, most notably Negishi, Suzuki–Miyaura, Stille, Kumada, and Hiyama couplings1,2. Despite the tremendous advances in C–C fragment couplings, the ability to forge C–O bonds in a general fashion via nickel catalysis has been largely unsuccessful. The challenge for nickel-mediated alcohol couplings has been the mechanistic requirement for the critical C–O bond forming step (formally known as the reductive elimination step) to occur via a Ni(III) alkoxide intermediate. In this manuscript, we demonstrate that visible light-excited photoredox catalysts can modulate the preferred oxidation states of nickel alkoxides in an operative catalytic cycle, thereby providing transient access to Ni(III) species that readily participate in reductive elimination. Using this synergistic merger of photoredox and nickel catalysis, we have developed a highly efficient and general carbon–oxygen coupling reaction using abundant alcohols and aryl bromides. More significantly, we have developed a general strategy to “switch on” important yet elusive organometallic mechanisms via oxidation state modulations using only weak light and single-electron transfer (SET) catalysts. PMID:26266976

Nonsymmetrical 3,4-dithienylmaleimides by cross-coupling reactions with indium organometallics: synthesis and photochemical studies.

PubMed

Mosquera, Angeles; Férnandez, M Isabel; Canle Lopez, Moisés; Pérez Sestelo, José; Sarandeses, Luis A

2014-10-27

The synthesis and photochemical study of novel nonsymmetrical 1,2-dithienylethenes (DTEs) with a maleimide bridge have been carried out. The synthetic approach to the DTEs was based on successive selective palladium-catalyzed cross-coupling reactions of 5-susbtituted-2-methyl-3-thiophenyl indium reagents with 3,4-dichloromaleimides. The required organoindium reagents were prepared from 2-methyl-3,5-dibromothiophene by a selective (C-5) coupling reaction with triorganoindium compounds (R3 In) and subsequent metal-halogen exchange. The coupling reactions usually gave good yields and have a high atom economy with substoichiometric amounts of R3 In. The results of photochemical studies show that these novel dithienylmaleimides undergo a photocyclization reaction upon irradiation in the UV region and a photocycloreversion after excitation in the visible region, thus they can be used as photochemical switches. ON-OFF operations can be repeated in successive cycles without appreciable loss of effectiveness in the process. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Solid-phase synthesis of smac peptidomimetics incorporating triazoloprolines and biarylalanines.

PubMed

Le Quement, Sebastian T; Ishoey, Mette; Petersen, Mette T; Thastrup, Jacob; Hagel, Grith; Nielsen, Thomas E

2011-11-14

Apoptotic induction mechanisms are of crucial importance for the general homeostasis of multicellular organisms. In cancer the apoptotic pathways are downregulated, which, at least partly, is due to an abundance of inhibitors of apoptosis proteins (IAPs) that block the apoptotic cascade by deactivating proteolytic caspases. The Smac protein has an antagonistic effect on IAPs, thus providing structural clues for the synthesis of new pro-apoptotic compounds. Herein, we report a solid-phase approach for the synthesis of Smac-derived tetrapeptide libraries. On the basis of a common (N-Me)AVPF sequence, peptides incorporating triazoloprolines and biarylalanines were synthesized by means of Cu(I)-catalyzed azide-alkyne cycloaddition and Pd-catalyzed Suzuki cross-coupling reactions. Solid-phase procedures were optimized to high efficiency, thus accessing all products in excellent crude purities and yields (both typically above 90%). The peptides were subjected to biological evaluation in a live/dead cellular assay which revealed that structural decorations on the AVPF sequence indeed are highly important for cytotoxicity toward HeLa cells.

An intramolecular [2 + 2] cycloaddition of ketenimines via palladium-catalyzed rearrangements of N-allyl-ynamides.

PubMed

DeKorver, Kyle A; Hsung, Richard P; Song, Wang-Ze; Wang, Xiao-Na; Walton, Mary C

2012-06-15

A cascade of Pd-catalyzed N-to-C allyl transfer-intramolecular ketenimine-[2 + 2] cycloadditions of N-allyl ynamides is described. This tandem sequence is highly stereoselective and the [2 + 2] cycloaddition could be rendered in a crossed or fused manner depending on alkene substitutions, leading to bridged and fused bicycloimines.

Forging Unsupported Metal-Boryl Bonds with Icosahedral Carboranes.

PubMed

Saleh, Liban M A; Dziedzic, Rafal M; Khan, Saeed I; Spokoyny, Alexander M

2016-06-13

In contrast to the plethora of metal-catalyzed cross-coupling methods available for the installation of functional groups on aromatic hydrocarbons, a comparable variety of methods are currently not available for icosahedral carboranes, which are boron-rich three-dimensional aromatic analogues of aryl groups. Part of this is due to the limited understanding of the elementary steps for cross-coupling involving carboranes. Here, we report our efforts in isolating metal-boryl complexes to further our understanding of one of these elementary steps, oxidative addition. Structurally characterized examples of group 10 M-B bonds featuring icosahedral carboranes are completely unknown. Use of mercurocarboranes as a reagent to deliver M-B bonds saw divergent reactivity for platinum and palladium, with a Pt-B bond being isolated for the former, and a rare Pd-Hg bond being formed for the latter. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Stereoselective Synthesis of Methylene Oxindoles via Palladium(II)-Catalyzed Intramolecular Cross-Coupling of Carbamoyl Chlorides.

PubMed

Le, Christine M; Sperger, Theresa; Fu, Rui; Hou, Xiao; Lim, Yong Hwan; Schoenebeck, Franziska; Lautens, Mark

2016-11-02

We report a highly robust, general and stereoselective method for the synthesis of 3-(chloromethylene)oxindoles from alkyne-tethered carbamoyl chlorides using PdCl 2 (PhCN) 2 as the catalyst. The transformation involves a stereo- and regioselective chloropalladation of an internal alkyne to generate a nucleophilic vinyl Pd II species, which then undergoes an intramolecular cross-coupling with a carbamoyl chloride. The reaction proceeds under mild conditions, is insensitive to the presence of moisture and air, and is readily scalable. The products obtained from this reaction are formed with >95:5 Z:E selectivity in nearly all cases and can be used to access biologically relevant oxindole cores. Through combined experimental and computational studies, we provide insight into stereo- and regioselectivity of the chloropalladation step, as well as the mechanism for the C-C bond forming process. Calculations provide support for a mechanism involving oxidative addition into the carbamoyl chloride bond to generate a high valent Pd IV species, which then undergoes facile C-C reductive elimination to form the final product. Overall, the transformation constitutes a formal Pd II -catalyzed intramolecular alkyne chlorocarbamoylation reaction.

Synthesis and structure-activity relationships of constrained heterocyclic analogues of combretastatin A4.

PubMed

Arthuis, Martin; Pontikis, Renée; Chabot, Guy G; Seguin, Johanne; Quentin, Lionel; Bourg, Stéphane; Morin-Allory, Luc; Florent, Jean-Claude

2011-09-05

A series of combretastatin A4 (CA4) analogues with a lactam or lactone ring fused to the trimethoxyphenyl or the B-phenyl moiety were synthesized in an efficient and stereoselective manner by using a domino Heck-Suzuki-Miyaura coupling reaction. The vascular-disrupting potential of these conformationally restricted CA4 analogues was assessed by various in vitro assays: inhibition of tubulin polymerization, modification of endothelial cell morphology, and disruption of endothelial cell cords. Compounds were also evaluated for their growth inhibitory effects against murine and human tumor cells. B-ring-constrained derivatives that contain an oxindole ring (in contrast to compounds with a benzofuranone ring) as well as analogues bearing a six-membered lactone core fused to the trimethoxyphenyl ring are endowed with significant biological activity. The most potent compound of this series (oxindole 9 b) is of particular interest, as it combines chemical stability and a biological activity profile characteristic of a vascular-disrupting agent. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

An Intramolecular [2 + 2] Cycloaddition of Ketenimines via Palladium-Catalyzed Rearrangements of N-Allyl-Ynamides

PubMed Central

DeKorver, Kyle A.; Song, Wang-Ze; Wang, Xiao-Na; Walton, Mary C.

2012-01-01

A cascade of Pd-catalyzed N-to-C allyl transfer–intramolecular ketenimine–[2 + 2] cycloadditions of N-allyl ynamides is described. This tandem sequence is highly stereoselective and the [2 + 2] cycloaddition could be rendered in a crossed or fused manner depending on alkene substitutions, leading to bridged and fused bicycloimines. PMID:22667819

Highly selective biaryl cross-coupling reactions between aryl halides and aryl Grignard reagents: a new catalyst combination of N-heterocyclic carbenes and iron, cobalt, and nickel fluorides.

PubMed

Hatakeyama, Takuji; Hashimoto, Sigma; Ishizuka, Kentaro; Nakamura, Masaharu

2009-08-26

Combinations of N-heterocyclic carbenes (NHCs) and fluoride salts of the iron-group metals (Fe, Co, and Ni) have been shown to be excellent catalysts for the cross-coupling reactions of aryl Grignard reagents (Ar(1)MgBr) with aryl and heteroaryl halides (Ar(2)X) to give unsymmetrical biaryls (Ar(1)-Ar(2)). Iron fluorides in combination with SIPr, a saturated NHC ligand, catalyze the biaryl cross-coupling between various aryl chlorides and aryl Grignard reagents in high yield and high selectivity. On the other hand, cobalt and nickel fluorides in combination with IPr, an unsaturated NHC ligand, exhibit interesting complementary reactivity in the coupling of aryl bromides or iodides; in contrast, with these substrates the iron catalysts show a lower selectivity. The formation of homocoupling byproducts is suppressed markedly to less than 5% in most cases by choosing the appropriate metal fluoride/NHC combination. The present catalyst combinations offer several synthetic advantages over existing methods: practical synthesis of a broad range of unsymmetrical biaryls without the use of palladium catalysts and phosphine ligands. On the basis of stoichiometric control experiments and theoretical studies, the origin of the unique catalytic effect of the fluoride counterion can be ascribed to the formation of a higher-valent heteroleptic metalate [Ar(1)MF(2)]MgBr as the key intermediate in our proposed catalytic cycle. First, stoichiometric control experiments revealed the stark differences in chemical reactivity between the metal fluorides and metal chlorides. Second, DFT calculations indicate that the initial reduction of di- or trivalent metal fluoride in the wake of transmetalation with PhMgCl is energetically unfavorable and that formation of a divalent heteroleptic metalate complex, [PhMF(2)]MgCl (M = Fe, Co, Ni), is dominant in the metal fluoride system. The heteroleptic ate-complex serves as a key reactive intermediate, which undergoes oxidative addition with PhCl and releases the biaryl cross-coupling product Ph-Ph with reasonable energy barriers. The present cross-coupling reaction catalyzed by iron-group metal fluorides and an NHC ligand provides a highly selective and practical method for the synthesis of unsymmetrical biaryls as well as the opportunity to gain new mechanistic insights into the metal-catalyzed cross-coupling reactions.

Design and application of sporopollenin microcapsule supported palladium catalyst: Remarkably high turnover frequency and reusability in catalysis of biaryls.

PubMed

Baran, Talat; Sargin, Idris; Kaya, Murat; Menteş, Ayfer; Ceter, Talip

2017-01-15

Bio-based catalyst support materials with high thermal and structural stability are desired for catalysts systems requiring harsh conditions. In this study, a thermally stable palladium catalyst (up to 440°C) was designed from sporopollenin, which occurs naturally in the outer exine layer of pollens and is widely acknowledged as chemically very stable and inert biological material. Catalyst design procedure included (1) extraction of sporopollenin microcapsules from Betula pendula pollens (∼25μm), (2) amino-functionalisation of the microcapsules, (3) Schiff base modification and (4) preparation of Pd(II) catalyst. The catalytic activity of the sporopollenin microcapsule supported palladium catalyst was tested in catalysis of biaryls by following a fast, simple and green microwave-assisted method. We recorded outstanding turnover number (TON: 40,000) and frequency (TOF: 400,000) for the catalyst in Suzuki coupling reactions. The catalyst proved to be reusable at least in eight cycles. The catalyst can be suggested for different catalyst systems due to its thermal and structural durability, reusability, inertness to air and its eco-friendly nature. Copyright © 2016 Elsevier Inc. All rights reserved.

Synthesis of Secondary Aromatic Amides via Pd-Catalyzed Aminocarbonylation of Aryl Halides Using Carbamoylsilane as an Amide Source.

PubMed

Tong, Wenting; Cao, Pei; Liu, Yanhong; Chen, Jianxin

2017-11-03

Using N-methoxymethyl-N-organylcarbamoyl(trimethyl)silanes as secondary amides source, the direct transformation of aryl halides into the corresponding secondary aromatic amides via palladium-catalyzed aminocarbonylation is described. The reactions tolerated a broad range of functional groups on the aryl ring except big steric hindrance of substituent. The types and the relative position of substituents on the aryl ring impact the coupling efficiency.

Silver and palladium alloy nanoparticle catalysts: reductive coupling of nitrobenzene through light irradiation.

PubMed

Peiris, Sunari; Sarina, Sarina; Han, Chenhui; Xiao, Qi; Zhu, Huai-Yong

2017-08-15

Silver-palladium (Ag-Pd) alloy nanoparticles strongly absorb visible light and exhibit significantly higher photocatalytic activity compared to both pure palladium (Pd) and silver (Ag) nanoparticles. Photocatalysts of Ag-Pd alloy nanoparticles on ZrO 2 and Al 2 O 3 supports are developed to catalyze the nitroaromatic coupling to the corresponding azo compounds under visible light irradiation. Ag-Pd alloy NP/ZrO 2 exhibited the highest photocatalytic activity for nitrobenzene coupling to azobenzene (yield of ∼80% in 3 hours). The photocatalytic efficiency could be optimized by altering the Ag : Pd ratio of the alloy nanoparticles, irradiation light intensity, temperature and wavelength. The rate of the reaction depends on the population and energy of the excited electrons, which can be improved by increasing the light intensity or by using a shorter wavelength. The knowledge developed in this study may inspire further studies on Ag alloy photocatalysts and organic syntheses using Ag-Pd nanoparticle catalysts driven under visible light Irradiation.

Alkyl–Alkyl Suzuki Cross-Couplings of Unactivated Secondary Alkyl Chlorides**

PubMed Central

Lu, Zhe; Fu, Gregory C.

2010-01-01

The first method for achieving alkyl–alkyl Suzuki reactions of unactivated secondary alkyl chlorides has been developed. Carbon–carbon bond formation occurs under mild conditions (at room temperature) with the aid of commercially available catalyst components. This method has proved to be versatile: without modification, it can be applied to Suzuki reactions of secondary and primary alkyl bromides and iodides, as well as primary alkyl chlorides. Mechanistic investigations suggest that oxidative addition is not the turnover-limiting step of the catalytic cycle for unactivated secondary alkyl iodides and bromides, whereas it may be (partially) for chlorides. PMID:20715038

Bimetallic catalysis involving dipalladium(I) and diruthenium(I) complexes.

PubMed

Das, Raj K; Saha, Biswajit; Rahaman, S M Wahidur; Bera, Jitendra K

2010-12-27

Dipalladium(I) and diruthenium(I) compounds bridged by two [{(5,7-dimethyl-1,8-naphthyridin-2-yl)amino}carbonyl]ferrocene (L) ligands have been synthesized. The X-ray structures of [Pd(2)L(2)][BF(4)](2) (1) and [Ru(2)L(2)(CO)(4)][BF(4)](2) (2) reveal dinuclear structures with short metal-metal distances. In both of these structures, naphthyridine bridges the dimetal unit, and the site trans to the metal-metal bond is occupied by weakly coordinating oxygen from the amido fragment. The catalytic utilities of these bimetallic compounds are evaluated. Compound 1 is an excellent catalyst for phosphine-free, Suzuki cross-coupling reactions of aryl bromides with arylboronic acids and provides high yields in short reaction times. Compound 1 is also found to be catalytically active for aryl chlorides, although the corresponding yields are lower. A bimetallic mechanism is proposed, which involves the oxidative addition of aryl bromide across the Pd-Pd bond and the bimetallic reductive elimination of the product. Compound 1 is also an efficient catalyst for the Heck cross-coupling of aryl bromides with styrenes. The mechanism for aldehyde olefination with ethyl diazoacetate (EDA) and PPh(3), catalyzed by 2, has been fully elucidated. It is demonstrated that 2 catalyzes the formation of phosphorane utilizing EDA and PPh(3), which subsequently reacts with aldehyde to produce a new olefin and phosphine oxide. The efficacy of bimetallic complexes in catalytic organic transformations is illustrated in this work.

Palladium-catalyzed hydroaminocarbonylation of alkenes with amines: a strategy to overcome the basicity barrier imparted by aliphatic amines.

PubMed

Zhang, Guoying; Gao, Bao; Huang, Hanmin

2015-06-22

A novel and efficient palladium-catalyzed hydroaminocarbonylation of alkenes with aminals has been developed under mild reaction conditions, and allows the synthesis of a wide range of N-alkyl linear amides in good yields with high regioselectivity. On the basis of this method, a cooperative catalytic system operating by the synergistic combination of palladium, paraformaldehyde, and acid was established for promoting the hydroaminocarbonylation of alkenes with both aromatic and aliphatic amines, which do not react well under conventional palladium-catalyzed hydroaminocarbonylation. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Bioorthogonal Diversification of Peptides through Selective Ruthenium(II)-Catalyzed C-H Activation.

PubMed

Schischko, Alexandra; Ren, Hongjun; Kaplaneris, Nikolaos; Ackermann, Lutz

2017-02-01

Methods for the chemoselective modification of amino acids and peptides are powerful techniques in biomolecular chemistry. Among other applications, they enable the total synthesis of artificial peptides. In recent years, significant momentum has been gained by exploiting palladium-catalyzed cross-coupling for peptide modification. Despite major advances, the prefunctionalization elements on the coupling partners translate into undesired byproduct formation and lengthy synthetic operations. In sharp contrast, we herein illustrate the unprecedented use of versatile ruthenium(II)carboxylate catalysis for the step-economical late-stage diversification of α- and β-amino acids, as well as peptides, through chemo-selective C-H arylation under racemization-free reaction conditions. The ligand-accelerated C-H activation strategy proved water-tolerant and set the stage for direct fluorescence labelling as well as various modes of peptide ligation with excellent levels of positional selectivity in a bioorthogonal fashion. The synthetic utility of our approach is further demonstrated by twofold C-H arylations for the complexity-increasing assembly of artificial peptides within a multicatalytic C-H activation manifold. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Total synthesis of (-)-strychnine.

PubMed

Kaburagi, Yosuke; Tokuyama, Hidetoshi; Fukuyama, Tohru

2004-08-25

Total synthesis of (-)-strychnine is described. Notable features of our synthesis include (1) palladium-catalyzed coupling of the indole and vinyl epoxide moieties, (2) synthesis of the nine-membered cyclic amine derivative from the diol precursor in a one-pot procedure, and (3) transannular cyclization of the nine-membered cyclic amine.

Stereoselective synthesis of tricyclic compounds by intramolecular palladium-catalyzed addition of aryl iodides to carbonyl groups

PubMed Central

Saadi, Jakub; Bentz, Christoph; Redies, Kai; Lentz, Dieter; Zimmer, Reinhold

2016-01-01

Summary Starting from γ-ketoesters with an o-iodobenzyl group we studied a palladium-catalyzed cyclization process that stereoselectively led to bi- and tricyclic compounds in moderate to excellent yields. Four X-ray crystal structure analyses unequivocally defined the structure of crucial cyclization products. The relative configuration of the precursor compounds is essentially transferred to that of the products and the formed hydroxy group in the newly generated cyclohexane ring is consistently in trans-arrangement with respect to the methoxycarbonyl group. A transition-state model is proposed to explain the observed stereochemical outcome. This palladium-catalyzed Barbier-type reaction requires a reduction of palladium(II) back to palladium(0) which is apparently achieved by the present triethylamine. PMID:27559374

Palladium-Catalyzed Atom-Transfer Radical Cyclization at Remote Unactivated C(sp3 )-H Sites: Hydrogen-Atom Transfer of Hybrid Vinyl Palladium Radical Intermediates.

PubMed

Ratushnyy, Maxim; Parasram, Marvin; Wang, Yang; Gevorgyan, Vladimir

2018-03-01

A novel mild, visible-light-induced palladium-catalyzed hydrogen atom translocation/atom-transfer radical cyclization (HAT/ATRC) cascade has been developed. This protocol involves a 1,5-HAT process of previously unknown hybrid vinyl palladium radical intermediates, thus leading to iodomethyl carbo- and heterocyclic structures. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Mechanistic Significance of the Si–O–Pd Bond in the Palladium-Catalyzed Cross-Coupling Reactions of Arylsilanolates

PubMed Central

2016-01-01

Through the combination of reaction kinetics (both stoichiometric and catalytic), solution- and solid-state characterization of arylpalladium(II) arylsilanolates, and computational analysis, the intermediacy of covalent adducts containing Si–O–Pd linkages in the cross-coupling reactions of arylsilanolates has been unambiguously established. Two mechanistically distinct pathways have been demonstrated: (1) transmetalation via a neutral 8-Si-4 intermediate that dominates in the absence of free silanolate (i.e., stoichiometric reactions of arylpalladium(II) arylsilanolate complexes), and (2) transmetalation via an anionic 10-Si-5 intermediate that dominates in the cross-coupling under catalytic conditions (i.e., in the presence of free silanolate). Arylpalladium(II) arylsilanolate complexes bearing various phosphine ligands have been isolated, fully characterized, and evaluated for their kinetic competence under thermal (stoichiometric) and anionic (catalytic) conditions. Comparison of the rates for thermal and anionic activation suggested, but did not prove, that intermediates containing the Si–O–Pd linkage were involved in the cross-coupling process. The isolation of a coordinatively unsaturated, T-shaped arylpalladium(II) arylsilanolate complex ligated with t-Bu3P allowed the unambiguous demonstration of the operation of both pathways involving 8-Si-4 and 10-Si-5 intermediates. Three kinetic regimes were identified: (1) with 0.5–1.0 equiv of added silanolate (with respect to arylpalladium bromide), thermal transmetalation via a neutral 8-Si-4 intermediate; (2) with 1.0–5.0 equiv of added silanolate, activated transmetalation via an anionic 10-Si-5 intermediate; and (3) with >5.0 equiv of added silanolate, concentration-independent (saturation) activated transmetalation via an anionic 10-Si-5 intermediate. Transition states for the intramolecular transmetalation of neutral (8-Si-4) and anionic (10-Si-5) intermediates have been located computationally, and the anionic pathway is favored by 1.8 kcal/mol. The energies of all intermediates and transition states are highly dependent on the configuration around the palladium atom. PMID:25945516

Synthesis and Catalytic Properties of Au Pd Nanoflowers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xu, Jianguang; Wilson, Adria; Howe, Jane Y

2011-01-01

Reduction of Pd ions by hydroquinone in the presence of gold nanoparticles and polyvinylpyrrolidone resulted in the formation of nanoflowers with a Au core and Pd petals. Addition of HCl to the synthesis halted the reduction by hydroquinone and enabled the acquisition of snapshots of the nanoflowers at different stages of growth. TEM images of the reaction after 10 s show that the nanoflower morphology resulted from the homogeneous nucleation of Pd clusters in solution and their subsequent attachment to gold seeds coated with a thin (0.8 0.1 nm) shell of Pd. UV visible spectra also indicate Pd clusters formedmore » in the early stages of the reaction and disappeared as the nanoflowers grew. The speed at which this reaction can be halted is useful not only for producing a variety of bimetallic nanostructures with precisely controlled dimensions and morphologies but also for understanding the growth mechanism of these structures. The ability of the AuPd core shell structure to catalyze the Suzuki coupling reaction of iodobenzene to phenylboronic acid was probed and compared against the activity of Pd nanocubes and thin-shelled AuPd core shell nanoparticles. The results of this study suggest that Suzuki coupling was not affected by the surface structure or subsurface composition of the nanoparticles, but instead was primarily catalyzed by molecular Pd species that leached from the nanostructures.« less

Synthesis of Au-Pd Nanoflowers Through Nanocluster Assembly

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xu, Jianguang; Howe, Jane Y; Chi, Miaofang

2011-01-01

Reduction of Pd ions by hydroquinone in the presence of gold nanoparticles and polyvinylpyrrolidone resulted in the formation of nanoflowers with a Au core and Pd petals. Addition of HCl to the synthesis halted the reduction by hydroquinone and enabled the acquisition of snapshots of the nanoflowers at different stages of growth. TEM images of the reaction after 10 s show that the nanoflower morphology resulted from the homogeneous nucleation of Pd clusters in solution and their subsequent attachment to gold seeds coated with a thin (0.8 {+-} 0.1 nm) shell of Pd. UV-visible spectra also indicate Pd clusters formedmore » in the early stages of the reaction and disappeared as the nanoflowers grew. The speed at which this reaction can be halted is useful not only for producing a variety of bimetallic nanostructures with precisely controlled dimensions and morphologies but also for understanding the growth mechanism of these structures. The ability of the AuPd core-shell structure to catalyze the Suzuki coupling reaction of iodobenzene to phenylboronic acid was probed and compared against the activity of Pd nanocubes and thin-shelled AuPd core-shell nanoparticles. The results of this study suggest that Suzuki coupling was not affected by the surface structure or subsurface composition of the nanoparticles, but instead was primarily catalyzed by molecular Pd species that leached from the nanostructures.« less

Palladium-Catalyzed Oxidative Couplings and Applications to the Synthesis of Macrocycles and Strained Cyclic Dienes

NASA Astrophysics Data System (ADS)

Boon, Byron Adrian

The palladium(II)-catalyzed oxidative macrocyclization of bis(vinylboronate esters) is demonstrated as an efficient method for the synthesis of macrocyclic dienes. The macrocyclization reactions feature mild conditions due to a palladium(II) catalytic cycle which obviates the need for a high energy oxidative addition step of standard palladium(0) catalytic cycles. Instead, this oxidative coupling is promoted by chloroacetone as a terminal re-oxidant in the catalytic cycle. An extension of the oxidative coupling/macrocyclization strategy is highlighted where molecular oxygen may be used in place of chloroacetone as the terminal re-oxidant. Homocoupling reactions of vinylboronate esters served as a template to screen reaction conditions for this method. From these experiments, multiple reaction conditions gave the oxidative homocoupling product in high yield. These reaction conditions were successfully applied to the oxidative macrocyclization of a bis(vinylboronate ester) using molecular oxygen as a re-oxidant. Syntheses of strained cyclic dienes were accomplished via the palladium(II)-catalyzed oxidative cyclizations of terminal bis(vinylboronate esters). The reactions generated strained (E,E)-1,3-dienes that underwent spontaneous 4?-electrocyclizations to form bicyclic cyclobutenes. Formation of the cyclobutenes is driven by strain in the medium-ring (E,E)-1,3-diene intermediates. Thermal ring openings of the cyclobutenes give (Z,Z)-1,3-diene products, again for thermodynamic reasons. These results are in contrast with typical acyclic trans-3,4-dialkyl cyclobutenes, which favor outward torquoselective ring-openings to give (E,E)-1,3-dienes. DFT calculations verified the thermodynamic versus kinetic control of the reactions and kinetic studies are in excellent agreement with the calculated energy changes. Investigations on the transannular Pauson-Khand reaction are also highlighted. The Pauson-Khand reaction is a powerful tool for the synthesis of cyclopentenones through the efficient [2+2+1] cycloaddition of dicobalt alkyne complexes with alkenes. While intermolecular and intramolecular variants are widely known, transannular versions of this reaction are unknown and the basis of this study. Our successful transannular Pauson-Khand reaction required a cyclic enyne incorporating one short three-membered linker chain and a rigid aryl linker in the backbone of the long linker chain. This rigidity of the aryl linker is proposed to facilitate the transannular [2+2+1] cyclization. Computational studies revealed that transannular Pauson-Khand reactions are thermodynamically favored for cyclic enynes featuring a long linker of at least 5 carbons, but with smaller chains the reactions are thermodynamically disfavored. Experimental studies show that long linking chains with more than 5 members are required to prevent to steric interactions between the dicobalt hexacarbonyl moiety and the linking chain to allow the reaction to be kinetically favored. The final part of this work highlights progress towards the total synthesis of (+)-kingianin A. This natural product was isolated as a racemic mixture from the bark of Endiandra kingiana and is an inhibitor of antiapoptotic protein Bcl-Xl, highlighting its potential use in cancer treatments. Its structure is proposed to arise from an intermolecular Diels-Alder dimerization reaction of bicyclo[4.2.0]octadiene fragments derived from an 8pi/6pi-electrocyclization cascade. Although two total syntheses of (+/-)-kingianin A have been reported, an enantioselective synthesis has not been achieved and is the purpose of this study. This synthetic route begins from L-(+)-dimethyl tartrate, a cheap and commercially available starting material, and aims to follow a biomimetic synthetic pathway featuring a substrate controlled diastereoselective palladium(II)-catalyzed oxidative cyclization and 8pi/6pi-electrocyclization cascade. Although the feasibility of this cascade pathway has not yet been realized, key synthetic transformations to install the requisite carbocyclic framework of (+)-kingianin A have been discovered, paving the way for future investigations on the palladium(II)-catalyzed coupling/electrocyclization cascade and completion of the synthesis.

Palladium-Catalyzed Formal Cross-Coupling of Diaryl Ethers with Amines: Slicing the 4-O-5 Linkage in Lignin Models.

PubMed

Zeng, Huiying; Cao, Dawei; Qiu, Zihang; Li, Chao-Jun

2018-03-26

Lignin is the second most abundant organic matter on Earth, and is an underutilized renewable source for valuable aromatic chemicals. For future sustainable production of aromatic compounds, it is highly desirable to convert lignin into value-added platform chemicals instead of using fossil-based resources. Lignins are aromatic polymers linked by three types of ether bonds (α-O-4, β-O-4, and 4-O-5 linkages) and other C-C bonds. Among the ether bonds, the bond dissociation energy of the 4-O-5 linkage is the highest and the most challenging to cleave. To date, 4-O-5 ether linkage model compounds have been cleaved to obtain phenol, cyclohexane, cyclohexanone, and cyclohexanol. The first example of direct formal cross-coupling of diaryl ether 4-O-5 linkage models with amines is reported, in which dual C(Ar)-O bond cleavages form valuable nitrogen-containing derivatives. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Supercritical CO{sub 2} mediated synthesis and catalytic activity of graphene/Pd nanocomposites

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tang, Lulu; Nguyen, Van Hoa; Department of Chemistry, Nha Trang University, 2 Nguyen Dinh Chieu, Nha Trang

2015-11-15

Highlights: • RGO/Pd composite was efficiently prepared via a facile method in supercritical CO{sub 2}. • Graphene sheets were coated uniformly with Pd nanoparticles with a size of ∼8 nm. • Composites exhibited excellent catalytic activity in the Suzuki reaction even after 10 cycles. - Abstract: Graphene sheets were decorated with palladium nanoparticles using a facile and efficient method in supercritical CO{sub 2}. The nanoparticles were formed on the graphene sheets by the simple hydrogen reduction of palladium(II) hexafluoroacetylacetonate precursor in supercritical CO{sub 2}. The product was characterized by X-ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy, transmission electronmore » microscopy, and X-ray photoelectron spectroscopy. Highly dispersed nanoparticles with various sizes and shapes adhered well to the graphene sheets. The composites showed high catalytic activities for the Suzuki reaction under aqueous and aerobic conditions within 5 min. The effects of the different Pd precursor loadings on the catalytic activities of the composites were also examined.« less

Rhodium-catalyzed redox-neutral coupling of phenidones with alkynes.

PubMed

Fan, Zhoulong; Lu, Heng; Li, Wei; Geng, Kaijun; Zhang, Ao

2017-07-21

A switchable synthesis of N-substituted indole derivatives from phenidones via rhodium-catalyzed redox-neutral C-H activation has been achieved. In this protocol, we firstly disclosed that the reactivity of Rh(iii) catalysis could be enhanced through employing palladium acetate as an additive. Some representative features include external oxidant-free, applicable to terminal alkynes, short reaction time and operational simplicity. The utility of this method is further showcased by the economical synthesis of potent anticancer PARP-1 inhibitors.

The Natural Product Magnolol as a Lead Structure for the Development of Potent Cannabinoid Receptor Agonists

PubMed Central

Müller, Christa E.

2013-01-01

Magnolol (4-allyl-2-(5-allyl-2-hydroxyphenyl)phenol), the main bioactive constituent of the medicinal plant Magnolia officinalis, and its main metabolite tetrahydromagnolol were recently found to activate cannabinoid (CB) receptors. We now investigated the structure-activity relationships of (tetrahydro)magnolol analogs with variations of the alkyl chains and the phenolic groups and could considerably improve potency. Among the most potent compounds were the dual CB1/CB2 full agonist 2-(2-methoxy-5-propyl-phenyl)-4-hexylphenol (61a, K i CB1∶0.00957 µM; K i CB2∶0.0238 µM), and the CB2-selective partial agonist 2-(2-hydroxy-5-propylphenyl)-4-pentylphenol (60, K i CB1∶0.362 µM; K i CB2∶0.0371 µM), which showed high selectivity versus GPR18 and GPR55. Compound 61b, an isomer of 61a, was the most potent GPR55 antagonist with an IC50 value of 3.25 µM but was non-selective. The relatively simple structures, which possess no stereocenters, are easily accessible in a four- to five-step synthetic procedure from common starting materials. The central reaction step is the well-elaborated Suzuki-Miyaura cross-coupling reaction, which is suitable for a combinatorial chemistry approach. The scaffold is versatile and may be fine-tuned to obtain a broad range of receptor affinities, selectivities and efficacies. PMID:24204944

Traceless Immobilization of Analytes for High-Throughput Experiments with SAMDI Mass Spectrometry.

PubMed

Helal, Kazi Y; Alamgir, Azmain; Berns, Eric J; Mrksich, Milan

2018-06-21

Label-free assays, and particularly those based on the combination of mass spectroscopy with surface chemistries, enable high-throughput experiments of a broad range of reactions. However, these methods can still require the incorporation of functional groups that allow immobilization of reactants and products to surfaces prior to analysis. In this paper, we report a traceless method for attaching molecules to a self-assembled monolayer for matrix-assisted laser desorption and ionization (SAMDI) mass spectrometry. This method uses monolayers that are functionalized with a 3-trifluoromethyl-3-phenyl-diazirine group that liberates nitrogen when irradiated and gives a carbene that inserts into a wide range of bonds to covalently immobilize molecules. Analysis of the monolayer with SAMDI then reveals peaks for each of the adducts formed from molecules in the sample. This method is applied to characterize a P450 drug metabolizing enzyme and to monitor a Suzuki-Miyaura coupling chemical reaction and is important because modification of the substrates with a functional group would alter their activities. This method will be important for high-throughput experiments in many areas, including reaction discovery and optimization.

Synthesis of 8-Aryl-O-methylcyanidins and Their Usage for Dye-Sensitized Solar Cell Devices.

PubMed

Kimura, Yuki; Oyama, Kin-Ichi; Murata, Yasujiro; Wakamiya, Atsushi; Yoshida, Kumi

2017-02-16

Anthocyanins as natural pigments are colorful and environmentally compatible dyes for dye-sensitized solar cells (DSSCs). To increase the efficiency, we designed and synthesized unnatural O -methylflavonols and O -methylcyanidins that possess an aryl group at the 8-position. We synthesized per - O -methylquercetin from quercetin, then using selective demethylation prepared various O -methylquercetins. Using the Suzuki-Miyaura coupling reaction, 8-arylation of per - O -methylquercetin was achieved. Using a LiAlH₄ reduction or Clemmensen reduction, these flavonols were transformed to the corresponding cyanidin derivatives in satisfactory yields. Using these dyes, we fabricated DSSCs, and their efficiency was investigated. The efficiency of tetra - O -methylflavonol was 0.31%. However, the introduction of the 8-aryl residue increased the efficiency to 1.04%. In comparison to these flavonols, O -methylcyanidins exhibited a lower efficiency of 0.05% to 0.52%. The introduction of the 8-aryl group into the cyanidin derivatives did not result in a remarkable increase in the efficiency. These phenomena may be due to the poor fit of the HOMO-LUMO level of the dyes to the TiO₂ conduction band.

Approaches to N-Methylwelwitindolinone C Isothiocyanate: Facile Synthesis of the Tetracyclic Core

PubMed Central

Heidebrecht, Richard W.; Gulledge, Brian; Martin, Stephen F.

2010-01-01

The synthesis of a functionalized, tetracyclic core of N-methylwelwitindolinone C isothiocyanate is reported. The approach features a convergent coupling between an indole iminium ion and a highly functionalized vinylogous silyl ketene acetal followed by an intramolecular palladium-catalyzed cyclization that proceeds via an enolate arylation. PMID:20446675

Laccases as palladium oxidases† †Electronic supplementary information (ESI) available: Experimental procedures, synthesis of catalysts molecules, enzyme activity assay, bleaching experiments, oxygraph traces, oxidation of veratryl alcohol assay, inhibition experiments, electrophoresis. See DOI: 10.1039/c4sc02564d Click here for additional data file.

PubMed Central

Schneider, Ludovic; Rousselot-Pailley, Pierre; Faure, Bruno; Simaan, A. Jalila; Bochot, Constance; Réglier, Marius

2015-01-01

The first example of a coupled catalytic system involving an enzyme and a palladium(ii) catalyst competent for the aerobic oxidation of alcohol in mild conditions is described. In the absence of dioxygen, the fungal laccase LAC3 is reduced by a palladium(0) species as evidenced by the UV/VIS and ESR spectra of the enzyme. During the oxidation of veratryl alcohol performed in water, at room temperature and atmospheric pressure, LAC3 regenerates the palladium catalyst, is reduced and catalyzes the four-electron reduction of dioxygen into water with no loss of enzyme activity. The association of a laccase with a water-soluble palladium complex results in a 7-fold increase in the catalytic efficiency of the complex. This is the first step in the design of a family of renewable palladium catalysts for aerobic oxidation. PMID:29560210

CuI/Pd0 cooperative dual catalysis: tunable stereoselective construction of tetra-substituted alkenes.

PubMed

Vercruysse, Sébastien; Cornelissen, Loïc; Nahra, Fady; Collard, Laurent; Riant, Olivier

2014-02-10

This paper describes a tunable and stereoselective dual catalytic system that uses copper and palladium reagents. This cooperative silylcupration and palladium-catalyzed allylation readily affords trisubstituted alkenylsilanes. Fine-tuning the reaction conditions allows selective access to one stereoisomer over the other. This new methodology tolerates different substituents on both coupling partners with high levels of stereoselectivity. The one-pot reaction involving a Cu(I)/Pd(0) cooperative dual catalyst directly addresses the need to develop more time-efficient and less-wasteful synthetic pathways. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A general approach to the synthesis of 5-S-functionalized pyrimidine nucleosides and their analogues.

PubMed

Kananovich, Dzmitry G; Reino, Alli; Ilmarinen, Kaja; Rõõmusoks, Marko; Karelson, Mati; Lopp, Margus

2014-08-14

A general and efficient approach was developed for the introduction of S-functionality at the C-5 position of cytosine and uracil nucleosides and their analogues. The key step is a palladium-catalyzed C-S coupling of the corresponding 5-bromo nucleoside derivative and alkyl thiol. The butyl 3-mercaptopropionate coupling products were further converted to the corresponding disulphides, the stable precursors of 5-mercaptopyrimidine nucleosides.

Synthesis of Bridged Oligophenylene Laser Dyes

DTIC Science & Technology

1991-05-10

the Grignard formation. Pure 22 as the free base could then be coulpled with the Grignard reagent from bromonaphthalene 20 using nickel acetoacetate as...preparation of 22 free of any positional isomer. We were able to prepare quite pure 22 by the Grignard coupling reaction of an excess p-chlorophenylmagnesium...fluorene 14 into the methoxyterphenyl 23 by the palladium-catalyzed Grignard coupling. Bromination of 23 was not clean as both the activated 7-position on

Palladium(ii)-catalyzed synthesis of dibenzothiophene derivatives via the cleavage of carbon–sulfur and carbon–hydrogen bonds† †Electronic supplementary information (ESI) available: Experimental procedures and characterization data for all new compounds. See DOI: 10.1039/c5sc04890g Click here for additional data file.

PubMed Central

Masuya, Yoshihiro; Baba, Katsuaki

2016-01-01

A new process has been developed for the palladium(ii)-catalyzed synthesis of dibenzothiophene derivatives via the cleavage of C–H and C–S bonds. In contrast to the existing methods for the synthesis of this scaffold by C–H functionalization, this new catalytic C–H/C–S coupling method does not require the presence of an external stoichiometric oxidant or reactive functionalities such as C–X or S–H, allowing its application to the synthesis of elaborate π-systems. Notably, the product-forming step of this reaction lies in an oxidative addition step rather than a reductive elimination step, making this reaction mechanistically uncommon. PMID:28660030

Polymerization of tellurophene derivatives via microwave-assisted palladium-catalyzed ipso-arylative polymerization**

PubMed Central

Park, Young S.; Wu, Qin; Nam, Chang-Yong; Grubbs, Robert B.

2014-01-01

We report the synthesis of a tellurophene-containing low bandgap polymer, PDPPTe2T, via microwave-assisted palladium-catalyzed ipso-arylative polymerization of 2,5-bis[(α-hydroxy-α,α-diphenyl)methyl]tellurophene with a diketopyrrolopyrrole (DPP) monomer. Compared with the corresponding thiophene analog, PDPPTe2T absorbs light of longer wavelengths and has a smaller bandgap. Bulk heterojunction solar cells prepared from PDPPTe2T and PC71BM show PCE values of up to 4.4%. External quantum efficiency measurements show that PDPPTe2T produces photocurrent at wavelengths up to 1 μm. DFT calculations suggest that the atomic substitution from sulfur to tellurium increases electronic coupling to decrease the length of the carbon-carbon bonds between the tellurophene and thiophene rings, which results in the red-shift in absorption upon substitution of tellurium for sulfur. PMID:25145499

Evolution of a strategy for preparing bioactive small molecules by sequential multicomponent assembly processes, cyclizations, and diversification.

PubMed

Sahn, James J; Granger, Brett A; Martin, Stephen F

2014-10-21

A strategy for generating diverse collections of small molecules has been developed that features a multicomponent assembly process (MCAP) to efficiently construct a variety of intermediates possessing an aryl aminomethyl subunit. These key compounds are then transformed via selective ring-forming reactions into heterocyclic scaffolds, each of which possesses suitable functional handles for further derivatizations and palladium-catalyzed cross coupling reactions. The modular nature of this approach enables the facile construction of libraries of polycyclic compounds bearing a broad range of substituents and substitution patterns for biological evaluation. Screening of several compound libraries thus produced has revealed a large subset of compounds that exhibit a broad spectrum of medicinally-relevant activities.

A general synthesis of C8-arylpurine phosphoramidites.

PubMed

Vongsutilers, Vorasit; Daft, Jonathan R; Shaughnessy, Kevin H; Gannett, Peter M

2009-09-02

A general scheme for the synthesis of C8-arylpurine phosphoramidites has been developed. C8-Arylation of C8-bromo-2'-deoxyguanosine is the key step and has been achieved through the use of a Suzuki coupling. Since the coupling reaction is conducted under aqueous conditions, it is unnecessary to protect and then deprotect the hydroxyl groups, thus saving several steps and improving overall yields. Once the C8-arylgroup is introduced, the glycosidic bond becomes very sensitive to acid catalyzed cleavage. Protection of the amino groups as the corresponding N,N-dimethylformamidine derivative improves stability of the derivatives. Synthetic C8-arylpurines were successfully used to prepare synthetic oligonucleotides.

Design, synthesis and antitubercular evaluation of novel 2-substituted-3H-benzofuro benzofurans via palladium-copper catalysed Sonagashira coupling reaction.

PubMed

Yempala, Thirumal; Sridevi, Jonnalagadda Padma; Yogeeswari, Perumal; Sriram, Darmarajan; Kantevari, Srinivas

2013-10-01

A series of novel natural product like 2-substiuted-3H-benzofurobenzofurans designed by molecular hybridization were synthesized in very good yields. The key reactions involved in the synthesis are iodination of 2-dibenzofuranol using iodine monochloride followed by palladium-copper catalyzed Sonagashira-coupling of 1-iododibenzofuran-2-ol with various alkyl and aryl acetylenes. Among the all 10 new compounds screened for in vitro anti-mycobacterial activity against Mycobacterium tuberculosis H37Rv, 2-(4-methoxy-2-methyl phenyl)-3H-benzofuro[3,2-e]benzofuran (7c) was found to be most active with MIC 3.12 μg/mL and has shown lower cytotoxicity with good therapeutic index. Copyright © 2013 Elsevier Ltd. All rights reserved.

Palladium-catalyzed substitution of (coumarinyl)methyl acetates with C-, N-, and S-nucleophiles

PubMed Central

Chattopadhyay, Kalicharan; Fenster, Erik; Grenning, Alexander J

2012-01-01

Summary The palladium-catalyzed nucleophilic substitution of (coumarinyl)methyl acetates is described. The reaction proceeds though a palladium π-benzyl-like complex and allows for many different types of C-, N-, and S-nucleophiles to be regioselectively added to the biologically active coumarin motif. This new method was utilized to prepare a 128-membered library of aminated coumarins for biological screening. PMID:23019448

Copper-catalyzed oxidative homo- and cross-coupling of Grignard reagents using diaziridinone.

PubMed

Zhu, Yingguang; Xiong, Tao; Han, Wenyong; Shi, Yian

2014-12-05

Transition-metal-catalyzed cross-coupling reactions are among the most powerful synthetic transformations. This paper describes an efficient copper-catalyzed homo- and cross-coupling of Grignard reagents with di-tert-butyldiaziridinone as oxidant under mild conditions, giving the coupling products in good to excellent yields. The reaction process has a broad substrate scope and is also effective for the C(sp)-C(sp(3)) coupling.

Ruthenium-Catalyzed Cycloaddition of 1-Haloalkynes with Nitrile Oxides and Organic Azides; Synthesis of 4-Halo Isoxazoles and 5-Halo Triazoles

PubMed Central

Oakdale, James S.; Sit, Rakesh K.

2015-01-01

(Cyclopentadienyl)(cyclooctadiene) ruthenium(II) chloride [CpRuCl(cod)] catalyzes the reaction between nitrile oxides and electronically deficient 1-choro-, 1-bromo- and 1-iodoalkynes leading to 4-haloisoxazoles. Organic azides are also suitable 1,3-dipoles, resulting in 5-halo-1,2,3-triazoles. These air tolerant reactions can be performed at room temperature with 1.25 equiv of the respective 1,3-dipole relative to the alkyne component. Reactive 1-haloalkynes include propiolic amides, esters, ketones and phosphonates. Post-functionalization of the halogenated azole products can be accomplished using palladium-catalyzed cross-coupling reactions as well as via manipulation of reactive amide groups. The lack of catalysis observed with Cp*RuCl(cod) is attributed to steric demands of the Cp* (η5-C5Me5) ligand in comparison to the parent Cp (η5-C5H5). This hypothesis is supported by the poor reactivity of (η5-C5Me4CF3)RuCl(cod), which serves as a an isosteric mimic of Cp* and as an isoelectronic analog of Cp. PMID:25059647

New Palladium-Catalyzed Approaches to Heterocycles and Carbocycles

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huang, Qinhua

2004-12-19

The tert-butylimines of o-(1-alkynyl)benzaldehydes and analogous pyridinecarbaldehydes have been cyclized under very mild reaction conditions in the presence of I 2, ICl, PhSeCl, PhSCl and p-O 2NC 6H 4SCl to give the corresponding halogen-, selenium- and sulfur-containing disubstituted isoquinolines and naphthyridines, respectively. Monosubstituted isoquinolines and naphthyridines have been synthesized by the metal-catalyzed ring closure of these same iminoalkynes. This methodology accommodates a variety of iminoalkynes and affords the anticipated heterocycles in moderate to excellent yields. The Pd(II)-catalyzed cyclization of 2-(1-alkynyl)arylaldimines in the presence of various alkenes provides an efficient way to synthesize a variety of 4-(1-alkenyl)-3-arylisoquinolines in moderate to excellentmore » yields. The introduction of an ortho-methoxy group on the arylaldimine promotes the Pd-catalyzed cyclization and stabilizes the resulting Pd(II) intermediate, improving the yields of the isoquinoline products. Highly substituted naphthalenes have been synthesized by the palladium-catalyzed annulation of a variety of internal alkynes, in which two new carbon-carbon bonds are formed in a single step under relatively mild reaction conditions. This method has also been used to synthesize carbazoles, although a higher reaction temperature is necessary. The process involves arylpalladation of the alkyne, followed by intramolecular Heck olefination and double bond isomerization. This method accommodates a variety of functional groups and affords the anticipated highly substituted naphthalenes and carbazoles in good to excellent yields. Novel palladium migratiodarylation methodology for the synthesis of complex fused polycycles has been developed, in which one or more sequential Pd-catalyzed intramolecular migration processes involving C-H activation are employed. The chemistry works best with electron-rich aromatics, which is in agreement with the idea that these palladium-catalyzed C-H activation reactions parallel electrophilic aromatic substitution. A relatively efficient synthesis of cyclopropanes has been developed using palladium-catalyzed C-H activation chemistry, in which two new carbon-carbon bonds are formed in a single step. This method involves the palladium-catalyzed activation of relatively unreactive C-H bonds, and provides a very efficient way to synthesize cyclopropapyrrolo[1,2-a]indoles, analogues of the mitomycin antibiotics.« less

PALLADIUM-CATALYZED OXIDATION OF STYRENE AND ALKENES IN PRESENCE OF IONIC LIQUIDS (WACKER REACTION)

EPA Science Inventory

The use of ionic liquids in various synthetic transformations is gaining significance due to the enhanced reaction rates, potential for recycling and compatibility with various organic compounds and organometallic catalysts. Palladium-catalyzed oxidation of styrene and other alk...

A Practical Method for the Vinylation of Aromatic Halides using Inexpensive Organosilicon Reagents

PubMed Central

Denmark, Scott E.; Butler, Christopher R.

2009-01-01

The preparation of styrenes by palladium-catalyzed cross-coupling of aromatic iodides and bromides with divinyltetramethyldisiloxane (DVDS) in the presence of inexpensive silanolate activators has been developed. To facilitate the discovery of optimal reaction conditions, Design of Experiment protocols were used. By the guided selection of reagents, stoichiometries, temperatures, and solvents the vinylation reaction was rapidly optimized with three stages consisting of ca. 175 experiments (of a possible 1440 combinations). A variety of aromatic iodides undergo cross-coupling at room temperature in the presence of potassium trimethylsilanoate using Pd(dba)2 in DMF in good yields. Triphenylphosphine oxide is needed to extend catalyst lifetime. Application of these conditions to aryl bromides was accomplished by the development of two complementary protocols. First, the direct implementation of the successful reaction conditions using aryl iodides at elevated temperature in THF provided the corresponding styrenes in good to excellent yields. Alternatively, the use of potassium triethylsilanolate and a bulky “Buchwald-type” ligand allows for the vinylation reactions to occur at or just above room temperature. A wide range of bromides underwent coupling in good yields for each of the protocols described. PMID:18303892

Discovering Green, Aqueous Suzuki Coupling Reactions: Synthesis of Ethyl (4-Phenylphenyl)Acetate, a Biaryl with Anti-Arthritic Potential

ERIC Educational Resources Information Center

Costa, Nancy E.; Pelotte, Andrea L.; Simard, Joseph M.; Syvinski, Christopher A.; Deveau, Amy M.

2012-01-01

Suzuki couplings are powerful chemical reactions commonly employed in academic and industrial research settings to generate functionalized biaryls. We have developed and implemented a discovery-based, microscale experiment for the undergraduate organic chemistry laboratory that explores green Suzuki coupling using water as the primary solvent.…

Copper-Catalyzed Oxidative Homo- and Cross-Coupling of Grignard Reagents Using Diaziridinone

PubMed Central

2015-01-01

Transition-metal-catalyzed cross-coupling reactions are among the most powerful synthetic transformations. This paper describes an efficient copper-catalyzed homo- and cross-coupling of Grignard reagents with di-tert-butyldiaziridinone as oxidant under mild conditions, giving the coupling products in good to excellent yields. The reaction process has a broad substrate scope and is also effective for the C(sp)–C(sp3) coupling. PMID:25420218

Synthesis of Nitriles via Palladium-Catalyzed Water Shuffling from Amides to Acetonitrile

PubMed Central

Zhang, Wandi; Haskins, Christopher W.; Yang, Yang; Dai, Mingji

2014-01-01

Palladium-catalyzed synthesis of nitriles from amides has been described. Two similar, but complementary reaction conditions have been identified to convert various amides including α,β,γ,δ-unsaturated amides, cinnamides, aromatic amides and alkyl amides to the corresponding nitriles in good to excellent yield. PMID:25316145

Synthesis of nitriles via palladium-catalyzed water shuffling from amides to acetonitrile.

PubMed

Zhang, Wandi; Haskins, Christopher W; Yang, Yang; Dai, Mingji

2014-12-07

Palladium-catalyzed synthesis of nitriles from amides has been described. Two similar, but complementary reaction conditions have been identified to convert various amides including α,β,γ,δ-unsaturated amides, cinnamides, aromatic amides and alkyl amides to the corresponding nitriles in good to excellent yield.

Palladium-Catalyzed Conversion of Aryl and Vinyl Triflates to Bromides and Chlorides

PubMed Central

Shen, Xiaoqiang; Hyde, Alan M.; Buchwald, Stephen L.

2010-01-01

The palladium-catalyzed conversion of aryl and vinyl triflates to aryl and vinyl halides (bromides and chlorides) has been developed using dialkylbiaryl phosphine ligands. A variety of aryl, heteroaryl and vinyl halides can be prepared via this method in good to excellent yields. PMID:20857936

Anthracene-Based Organic Small-Molecule Electron-Injecting Material for Inverted Organic Light-Emitting Diodes.

PubMed

Matsuo, Yutaka; Okada, Hiroshi; Kondo, Yasuhiro; Jeon, Il; Wang, Huan; Yu, Yun; Matsushita, Takeshi; Yanai, Motoki; Ikuta, Toshiaki

2018-04-11

A diphenylanthracene dimethylamine derivative (9-{3,5-di( N, N-dimethylaminoethoxy)phenyl}-10-phenyl-anthracene, DPAMA) was synthesized by the Suzuki-Miyaura cross-coupling reaction. Its ammonium salt, 9-{3,5-di(trimethylammonium ethoxy)phenyl}-10-phenyl-anthracene dichloride (DPAMA-Cl), was also synthesized as a reference material. DPAMA was characterized by UV-vis and fluorescence spectroscopy, cyclic voltammetry, photoelectron yield spectroscopy, and X-ray photoelectron spectroscopy to evaluate the work function-modifying ability of DPAMA on indium tin oxide (ITO) and ZnO. The work functions of ITO and ZnO changed from 4.4 and 4.0 eV (pristine) to 3.8 and 3.9 eV, respectively. Using this surface modification effect of DPAMA, inverted organic light-emitting diodes were fabricated with device structures of ITO/DPAMA/Alq 3 /NPD/MoO 3 /Al (Alq 3 = tris(8-hydroxyquinolinato)aluminum; NPD = N, N'-di-[(1-naphthyl)- N, N'-diphenyl]-1,1'-(biphenyl)-4,4'-diamine) and ITO/ZnO/DPAMA/Alq 3 /NPD/MoO 3 /Al. Both devices showed good performance at the range of current density, 1-300 mA/cm 2 . The best inverted organic light-emitting diodes device showed luminance of 7720 cd/m 2 , current efficiency of 4.51 cd/A, and external quantum efficiency of 1.45%. Also, poly(3-hexylthiophene):mixed phenyl-C 61 and C 71 butyric acid methyl ester-based organic solar cells using DPAMA and DPAMA-Cl as electron-transporting materials showed power conversion efficiencies of 3.3 and 3.4%, respectively.

Symmetrical and unsymmetrical pincer complexes with group 10 metals: synthesis via aryl C-H activation and some catalytic applications.

PubMed

Niu, Jun-Long; Hao, Xin-Qi; Gong, Jun-Fang; Song, Mao-Ping

2011-05-21

Aryl-based pincer metal complexes with anionic terdentate ligands have been widely applied in organic synthesis, organometallic catalysis and other related areas. Synthetically, the most simple and convenient method for the construction of these complexes is the direct metal-induced C(aryl)-H bond activation, which can be fulfilled by choosing the appropriate functional donor groups in the two side arms of the aryl-based pincer preligands. In this perspective, we wish to summarize some results achieved by our group in this context. Successful examples include symmetrical chiral bis(imidazoline) NCN pincer complexes with Ni(II), Pd(II) and Pt(II), bis(phosphinite) and bis(phosphoramidite) PCP pincer Pd(II) complexes, unsymmetrical (pyrazolyl)phosphinite, (amino)phosphinite and (imino)phosphinite PCN pincer Pd(II) complexes, chiral (imidazolinyl)phosphinite and (imidazolinyl)phosphoramidite PCN pincer complexes with Ni(II) and Pd(II) as well as unsymmetrical (oxazolinyl)amine and (oxazolinyl)pyrazole NCN' pincer Pd(II) complexes. Among them, the P-donor containing complexes are efficiently synthesized by the "one-pot phosphorylation/metalation" method. The obtained symmetrical and unsymmetrical pincer complexes have been used as catalysts in Suzuki-Miyaura reaction (Pd), asymmetric Friedel-Crafts alkylation of indole with trans-β-nitrostyrene (Pt) as well as in asymmetric allylation of aldehyde and sulfonimine (Pd). In the Suzuki couplings conducted at 40-50 °C, some unsymmetrical Pd complexes exhibit much higher activity than the related symmetrical ones which can be attributed to their faster release of active Pd(0) species resulting from the hemilabile coordination of the ligands. Literature results on the synthesis of some related pincer complexes as well as their activities in the above catalytic reactions are also presented.

Maghemite decorated with ultra-small palladium nanoparticles (γ-Fe2O3–Pd): applications in the Heck–Mizoroki olefination, Suzuki reaction and allylic oxidation of alkenes

EPA Science Inventory

A nanocatalyst comprising ultra-small Pd/PdO nanoparticles (<5 nm) supported on maghemite was prepared by a co-precipitation protocol using inexpensive raw materials and was deployed successfully in various significant synthetic transformations, namely the Heck–Mizoroki olefinati...

Pd(OAc)2-Catalyzed Domino Reactions of 1-Chloro-2-Haloarenes and 2-Haloaryl Tosylates with Hindered Grignard Reagents via Palladium Associated Arynes

PubMed Central

Dong, Cheng-Guo; Hu, Qiao-Sheng

2008-01-01

The palladium associated aryne generation strategy and Pd(OAc)2-catalyzed annulative Domino reactions of 1-chloro-2-halobenzenes and 2-haloaryl tosylates with hindered Grignard reagents via palladium associated arynes are described. The palladium associated aryne generation strategy described here not only allows the high yield, one-step access to potentially useful substituted fluorenes from readily available 1-chloro-2-halobenzenes and 2-haloaryl tosylates, but may also lead to the development of other tandem reactions based on these readily available o-leaving group bearing haloarenes PMID:17048842

Pd(OAc)(2)-catalyzed Domino reactions of 1-chloro-2-haloarenes and 2-haloaryl tosylates with hindered Grignard reagents via palladium-associated arynes.

PubMed

Dong, Cheng-Guo; Hu, Qiao-Sheng

2006-10-26

The palladium-associated aryne generation strategy and Pd(OAc)(2)-catalyzed annulative Domino reactions of 1-chloro-2-halobenzenes and 2-haloaryl tosylates with hindered Grignard reagents via palladium-associated arynes are described. The palladium-associated aryne generation strategy described here not only allows the high yield, one-step access to potentially useful substituted fluorenes from readily available 1-chloro-2-halobenzenes and 2-haloaryl tosylates, but may also lead to the development of other tandem reactions based on these readily available ortho leaving group bearing haloarenes. [reaction: see text

Synthesis of 8-Aryl-O-methylcyanidins and Their Usage for Dye-Sensitized Solar Cell Devices

PubMed Central

Kimura, Yuki; Oyama, Kin-ichi; Murata, Yasujiro; Wakamiya, Atsushi; Yoshida, Kumi

2017-01-01

Anthocyanins as natural pigments are colorful and environmentally compatible dyes for dye-sensitized solar cells (DSSCs). To increase the efficiency, we designed and synthesized unnatural O-methylflavonols and O-methylcyanidins that possess an aryl group at the 8-position. We synthesized per-O-methylquercetin from quercetin, then using selective demethylation prepared various O-methylquercetins. Using the Suzuki-Miyaura coupling reaction, 8-arylation of per-O-methylquercetin was achieved. Using a LiAlH4 reduction or Clemmensen reduction, these flavonols were transformed to the corresponding cyanidin derivatives in satisfactory yields. Using these dyes, we fabricated DSSCs, and their efficiency was investigated. The efficiency of tetra-O-methylflavonol was 0.31%. However, the introduction of the 8-aryl residue increased the efficiency to 1.04%. In comparison to these flavonols, O-methylcyanidins exhibited a lower efficiency of 0.05% to 0.52%. The introduction of the 8-aryl group into the cyanidin derivatives did not result in a remarkable increase in the efficiency. These phenomena may be due to the poor fit of the HOMO-LUMO level of the dyes to the TiO2 conduction band. PMID:28212330

Palladium-Catalyzed α-Arylation of Zinc Enolates of Esters: Reaction Conditions and Substrate Scope

PubMed Central

Hama, Takuo; Ge, Shaozhong; Hartwig, John F.

2013-01-01

The intermolecular α-arylation of esters by palladium-catalyzed coupling of aryl bromides with zinc enolates of esters is reported. Reactions of three different types of zinc enolates have been developed. α-Arylation of esters occurs in high yields with isolated Reformatsky reagents, with Reformatsky reagents generated from α-bromo esters and activated zinc, and with zinc enolates generated by quenching lithium enolates of esters with zinc chloride. The use of zinc enolates, instead of alkali metal enolates, greatly expands the scope of the arylation of esters. The reactions occur at room temperature or at 70 °C with bromoarenes containing cyano, nitro, ester, keto, fluoro, enolizable hydrogen, hydroxyl or amino functionality and with bromopyridines. The scope of esters encompasses acyclic acetates, propionates, and isobutyrates, α-alkoxyesters, and lactones. The arylation of zinc enolates of esters was conducted with catalysts bearing the hindered pentaphenylferrocenyl di-tert-butylphosphine (Q-phos) or the highly reactive dimeric Pd(I) complex {[P(t-Bu)3]PdBr}2. PMID:23931445

Practical Iron- and Cobalt-Catalyzed Cross-Coupling Reactions between N-Heterocyclic Halides and Aryl or Heteroaryl Magnesium Reagents.

PubMed

Kuzmina, Olesya M; Steib, Andreas K; Fernandez, Sarah; Boudot, Willy; Markiewicz, John T; Knochel, Paul

2015-05-26

The reaction scope of iron- and cobalt-catalyzed cross-coupling reactions in the presence of isoquinoline (quinoline) in the solvent mixture tBuOMe/THF has been further investigated. Various 2-halogenated pyridine, pyrimidine, and triazine derivatives were arylated under these mild conditions in excellent yields. The presence of isoquinoline allows us to perform Fe-catalyzed cross-coupling reactions between 6-chloroquinoline and aryl magnesium reagents. Furthermore, it was found that the use of 10% N,N-dimethylquinoline-8-amine increases the yields of some Co-catalyzed cross-coupling reactions with chloropyridines bearing electron-withdrawing substituents. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Sequence-defined oligo(ortho-arylene) foldamers derived from the benzannulation of ortho(arylene ethynylene)s† †Electronic supplementary information (ESI) available. CCDC 1483959–1483967. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c6sc02520j Click here for additional data file. Click here for additional data file.

PubMed Central

Lehnherr, Dan; Chen, Chen; Pedramrazi, Zahra; DeBlase, Catherine R.; Alzola, Joaquin M.; Keresztes, Ivan; Lobkovsky, Emil B.

2016-01-01

A Cu-catalyzed benzannulation reaction transforms ortho(arylene ethynylene) oligomers into ortho-arylenes. This approach circumvents iterative Suzuki cross-coupling reactions previously used to assemble hindered ortho-arylene backbones. These derivatives form helical folded structures in the solid-state and in solution, as demonstrated by X-ray crystallography and solution-state NMR analysis. DFT calculations of misfolded conformations are correlated with variable-temperature 1H and EXSY NMR to reveal that folding is cooperative and more favorable in halide-substituted naphthalenes. Helical ortho-arylene foldamers with specific aromatic sequences organize functional π-electron systems into arrangements ideal for ambipolar charge transport and show preliminary promise for the surface-mediated synthesis of structurally defined graphene nanoribbons. PMID:28567248

N-Methylamino Pyrimidyl Amides (MAPA): Highly Reactive, Electronically-Activated Amides in Catalytic N-C(O) Cleavage.

PubMed

Meng, Guangrong; Lalancette, Roger; Szostak, Roman; Szostak, Michal

2017-09-01

Despite recent progress in catalytic cross-coupling technologies, the direct activation of N-alkyl-N-aryl amides has been a challenging transformation. Here, we report the first Suzuki cross-coupling of N-methylamino pyrimidyl amides (MAPA) enabled by the controlled n N → π Ar conjugation and the resulting remodeling of the partial double bond character of the amide bond. The new mode of amide activation is suitable for generating acyl-metal intermediates from unactivated primary and secondary amides.

Palladium-catalyzed three-component reaction of N-tosyl hydrazones, isonitriles and amines leading to amidines.

PubMed

Dai, Qiang; Jiang, Yan; Yu, Jin-Tao; Cheng, Jiang

2015-12-04

A palladium-catalyzed three-component reaction between N-tosyl hydrazones, aryl isonitriles and amines was developed, leading to amidines in moderate to good yields. This procedure features the rapid construction of amidine frameworks with high diversity and complexity. Ketenimines serve as intermediates, which encounter nucleophilic attack by amines to produce amidines.

Palladium-Catalyzed Coupling of Ammonia with Aryl Chlorides, Bromides, Iodides and Sulfonates: A General Method for the Preparation of Primary Arylamines

PubMed Central

Vo, Giang D.

2010-01-01

We report that the complex generated from Pd[P(o-tol)3]2 and the alkylbisphosphine CyPF-t-Bu is a highly active and selective catalyst for the coupling of ammonia with aryl chlorides, bromides, iodides, and sulfonates. The couplings of ammonia with this catalyst conducted with a solution of ammonia in dioxane form primary arylamines from a variety of aryl electrophiles in high yields. Catalyst loadings as low as 0.1 mol % were sufficient for reactions of many aryl chlorides and bromides. In the presence of this catalyst, aryl sulfonates also coupled with ammonia for the first time in high yields. A comparison of reactions in the presence of this catalyst versus those in the presence of existing copper and palladium systems revealed a complementary, if not broader substrate scope. The utility of this method to generate amides, imides and carbamates is illustrated by a one-pot synthesis of a small library of these carbonyl compounds from aryl bromides and chlorides. Mechanistic studies show that Pd[P(o-tol)3]2 and CyPF-t-Bu generate a more active and general catalyst than that generated from CyPF-t-Bu and palladiun(II) precursors because of the low concentration of active catalyst that is generated from the combination of palladium(II), ammonia and base. PMID:19591470

Lewis Acid Catalyzed Asymmetric Three-Component Coupling Reaction: Facile Synthesis of α-Fluoromethylated Tertiary Alcohols.

PubMed

Aikawa, Kohsuke; Kondo, Daisuke; Honda, Kazuya; Mikami, Koichi

2015-12-01

A chiral dicationic palladium complex is found to be an efficient Lewis acid catalyst for the synthesis of α-fluoromethyl-substituted tertiary alcohols using a three-component coupling reaction. The reaction transforms three simple and readily available components (terminal alkyne, arene, and fluoromethylpyruvate) to valuable chiral organofluorine compounds. This strategy is completely atom-economical and results in perfect regioselectivities and high enantioselectivities of the corresponding tertiary allylic alcohols in good to excellent yields. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Conversion of Arylboronic Acids to Tetrazoles Catalyzed by ONO Pincer-Type Palladium Complex.

PubMed

Vignesh, Arumugam; Bhuvanesh, Nattamai S P; Dharmaraj, Nallasamy

2017-01-20

A convenient synthesis of a library of tetrazoles through a novel and operationally simple protocol effecting the direct conversion of arylboronic acids catalyzed by a new ONO pincer-type Pd(II) complex under mild reaction conditions using the readily available reagents is reported. The palladium complex was reused up to four cycles in an open-flask condition.

Palladium-catalyzed cocyclotrimerization of arynes with a pyramidalized alkene.

PubMed

Alonso, José M; Quiroga, Sabela; Codony, Sandra; Turcu, Andreea L; Barniol-Xicota, Marta; Pérez, Dolores; Guitián, Enrique; Vázquez, Santiago; Peña, Diego

2018-05-23

The metal-catalyzed [2+2+2] cocycloaddition of arynes with pyramidalized alkenes is presented. The generation of a highly reactive pyramidalized alkene in the presence of a large excess of in situ-produced arynes led to the corresponding cocyclotrimerization (1 : 2)-adducts in good yields, establishing the first example of a palladium-based reaction of a pyramidalized alkene.

Palladium-Catalyzed SN2'-Cyclization of Ambivalent (Bromoalkadienyl)malonates: Preparation of Medium- to Large-Membered Endocyclic Allenes.

PubMed

Ichio, Hiroaki; Murakami, Hidetoshi; Chen, Yen-Chou; Takahashi, Tamotsu; Ogasawara, Masamichi

2017-07-21

A palladium-catalyzed reaction for preparing various endocyclic allenes was developed. The substrates for the reaction were readily available ω-(pronucleophile-tethered)-3-bromo-1,3-alkadienes, and a palladium-catalyst facilitated their unimolecular S N 2'-cyclization in the presence of potassium tert-butoxide to give the corresponding 9- to 16-membered endocyclic allenes in fair yields of up to 67% together with the dimeric 16- to 32-membered endocyclic bis-allenes and other oligomeric/polymeric intermolecular reaction products. For higher yields of the monomeric endocyclic allenes, the reaction needed to be conducted under high-dilution conditions. Using a chiral palladium catalyst, axially chiral endocyclic allenes were obtained in up to 70% ee.

Nickel-catalyzed cross-coupling of photoredox-generated radicals: uncovering a general manifold for stereoconvergence in nickel-catalyzed cross-couplings.

PubMed

Gutierrez, Osvaldo; Tellis, John C; Primer, David N; Molander, Gary A; Kozlowski, Marisa C

2015-04-22

The cross-coupling of sp(3)-hybridized organoboron reagents via photoredox/nickel dual catalysis represents a new paradigm of reactivity for engaging alkylmetallic reagents in transition-metal-catalyzed processes. Reported here is an investigation into the mechanistic details of this important transformation using density functional theory. Calculations bring to light a new reaction pathway involving an alkylnickel(I) complex generated by addition of an alkyl radical to Ni(0) that is likely to operate simultaneously with the previously proposed mechanism. Analysis of the enantioselective variant of the transformation reveals an unexpected manifold for stereoinduction involving dynamic kinetic resolution (DKR) of a Ni(III) intermediate wherein the stereodetermining step is reductive elimination. Furthermore, calculations suggest that the DKR-based stereoinduction manifold may be responsible for stereoselectivity observed in numerous other stereoconvergent Ni-catalyzed cross-couplings and reductive couplings.

Ligand-free palladium-mediated site-specific protein labeling inside gram-negative bacterial pathogens.

PubMed

Li, Jie; Lin, Shixian; Wang, Jie; Jia, Shang; Yang, Maiyun; Hao, Ziyang; Zhang, Xiaoyu; Chen, Peng R

2013-05-15

Palladium, a key transition metal in advancing modern organic synthesis, mediates diverse chemical conversions including many carbon-carbon bond formation reactions between organic compounds. However, expanding palladium chemistry for conjugation of biomolecules such as proteins, particularly within their native cellular context, is still in its infancy. Here we report the site-specific protein labeling inside pathogenic Gram-negative bacterial cells via a ligand-free palladium-mediated cross-coupling reaction. Two rationally designed pyrrolysine analogues bearing an aliphatic alkyne or an iodophenyl handle were first encoded in different enteric bacteria, which offered two facial handles for palladium-mediated Sonogashira coupling reaction on proteins within these pathogens. A GFP-based bioorthogonal reaction screening system was then developed, allowing evaluation of both the efficiency and the biocompatibilty of various palladium reagents in promoting protein-small molecule conjugation. The identified simple compound-Pd(NO3)2 exhibited high efficiency and biocompatibility for site-specific labeling of proteins in vitro and inside living E. coli cells. This Pd-mediated protein coupling method was further utilized to label and visualize a Type-III Secretion (T3S) toxin-OspF in Shigella cells. Our strategy may be generally applicable for imaging and tracking various virulence proteins within Gram-negative bacterial pathogens.

Palladium-catalyzed double carbonylation using near stoichiometric carbon monoxide: expedient access to substituted 13C2-labeled phenethylamines.

PubMed

Nielsen, Dennis U; Neumann, Karoline; Taaning, Rolf H; Lindhardt, Anders T; Modvig, Amalie; Skrydstrup, Troels

2012-07-20

A novel and general approach for (13)C(2)- and (2)H-labeled phenethylamine derivatives has been developed, based on a highly convergent single-step assembly of the carbon skeleton. The efficient incorporation of two carbon-13 isotopes into phenethylamines was accomplished using a palladium-catalyzed double carbonylation of aryl iodides with near stoichiometric carbon monoxide.

Et3B-mediated and palladium-catalyzed direct allylation of β-dicarbonyl compounds with Morita–Baylis–Hillman alcohols

PubMed Central

Abidi, Ahlem; Oueslati, Yosra

2016-01-01

A practical and efficient palladium-catalyzed direct allylation of β-dicarbonyl compounds with both cyclic and acyclic Morita–Baylis–Hillman (MBH) alcohols, using Et3B as a Lewis acid promoter, is described herein. A wide range of the corresponding functionalized allylated derivatives have been obtained in good yields and with high selectivity. PMID:28144308

Novel [(biphenyloxy)propyl]isoxazole derivatives for inhibition of human rhinovirus 2 and coxsackievirus B3 replication.

PubMed

Makarov, Vadim A; Riabova, Olga B; Granik, Vladimir G; Wutzler, Peter; Schmidtke, Michaela

2005-04-01

During this study, novel biphenyl derivatives were synthesized and tested for antiviral activity. A new method based on the Suzuki coupling reaction has been established for the synthesis of these polysubstituted chain systems. In parallel with cytotoxicity, the antiviral activity of biphenyl derivatives has been determined in cytopathic effect (CPE)-inhibitory assays with the pleconaril-resistant coxsackievirus B3 (CVB3) strain Nancy, human rhinovirus 2 (HRV-2) and 14 (HRV-14) and in plaque reduction assays with the pleconaril-sensitive human isolate CVB3 97-927 in HeLa cells. Based on the results from these investigations the selectivity index (SI) was determined as the ratio of the 50% cytotoxic concentration to the 50% inhibitory concentration. The new method based on the Suzuki coupling reaction includes the condensation of 2,6-dimethyl-4-bromophenol with pentyne chloride by means of potassium carbonate and potassium iodide in N-methylpyrrolidone-2 and yields 5-bromo-1,3-dimethyl-2-(4-pentynyloxy)benzene. Its condensation with methylacetaldoxime results in 3-methylisoxazole derivatives. The following reaction with different benzeneboronic acids by means of tetrakis(triphenylphosphine)-palladium(0) finally yields the corresponding derivatives. Several of the novel synthesized derivatives demonstrated a good antiviral activity on CVB3 (SI > 2 to > 37.5) and a strong anti-HRV-2 activity (SI > 50 to > 200). In contrast, none of the compounds inhibited the HRV-14-induced CPE. These results indicate that [(biphenyloxy)propyl]isoxazole derivatives are potential inhibitors of HRV-2 and CVB3 replication, and make them promising agents for the specific treatment of these virus infections.

Enhancing the performance of single-chambered microbial fuel cell using manganese/palladium and zirconium/palladium composite cathode catalysts.

PubMed

Jadhav, Dipak A; Deshpande, Parag A; Ghangrekar, Makarand M

2017-08-01

Application of ZrO 2 , MnO 2 , palladium, palladium-substituted-zirconium oxide (Zr 0.98 Pd 0.02 O 2 ) and palladium-substituted-manganese oxide (Mn 0.98 Pd 0.02 O 2 ) cathode catalysts in a single-chambered microbial fuel cell (MFC) was explored. The highest power generation (1.28W/m 3 ) was achieved in MFC with Mn 0.98 Pd 0.02 O 2 catalyst, which was higher than that with MnO 2 (0.58W/m 3 ) alone; whereas, MFC having Zr 0.98 Pd 0.02 O 2 catalyzed cathode and non-catalyzed cathode produced powers of 1.02 and 0.23W/m 3 , respectively. Also, low-cost zirconium-palladium-composite showed better catalytic activity and capacitance over ZrO 2 with 20A/m 3 current production and demonstrated its suitability for MFC applications. Cyclic voltammetry analyses showed higher well-defined redox peaks in composite catalysts (Mn/Zr-Pd-C) over other catalyzed MFCs containing MnO 2 or ZrO 2 . Electrochemical behaviour of composite catalysts on cathode showed higher availability of adsorption sites for oxygen reduction and, hence, enhanced the rate of cathodic reactions. Thus, Mn/Zr-Pd-C-based composite catalysts exhibited superior cathodic performance and could be proposed as alternatives to costly Pd-catalyst for field applications. Copyright © 2017 Elsevier Ltd. All rights reserved.

Heterogeneous Pd catalysts as emulsifiers in Pickering emulsions for integrated multistep synthesis in flow chemistry

PubMed Central

Hiebler, Katharina; Lichtenegger, Georg J; Maier, Manuel C; Park, Eun Sung; Gonzales-Groom, Renie

2018-01-01

Within the “compartmentalised smart factory” approach of the ONE-FLOW project the implementation of different catalysts in “compartments” provided by Pickering emulsions and their application in continuous flow is targeted. We present here the development of heterogeneous Pd catalysts that are ready to be used in combination with biocatalysts for catalytic cascade synthesis of active pharmaceutical ingredients (APIs). In particular, we focus on the application of the catalytic systems for Suzuki–Miyaura cross-coupling reactions, which is the key step in the synthesis of the targeted APIs valsartan and sacubitril. An immobilised enzyme will accomplish the final product formation via hydrolysis. In order to create a large interfacial area for the catalytic reactions and to keep the reagents separated until required, the catalyst particles are used to stabilise Pickering emulsions of oil and water. A set of Ce–Sn–Pd oxides with the molecular formula Ce0.99− xSnxPd0.01O2−δ (x = 0–0.99) has been prepared utilising a simple single-step solution combustion method. The high applicability of the catalysts for different functional groups and their minimal leaching behaviour is demonstrated with various Suzuki–Miyaura cross-coupling reactions in batch as well as in continuous flow employing the so-called “plug & play reactor”. Finally, we demonstrate the use of these particles as the sole emulsifier of oil–water emulsions for a range of oils. PMID:29623127

Palladium-catalyzed coupling of ammonia with aryl chlorides, bromides, iodides, and sulfonates: a general method for the preparation of primary arylamines.

PubMed

Vo, Giang D; Hartwig, John F

2009-08-12

We report that the complex generated from Pd[P(o-tol)(3)](2) and the alkylbisphosphine CyPF-t-Bu is a highly active and selective catalyst for the coupling of ammonia with aryl chlorides, bromides, iodides, and sulfonates. The couplings of ammonia with this catalyst conducted with a solution of ammonia in dioxane form primary arylamines from a variety of aryl electrophiles in high yields. Catalyst loadings as low as 0.1 mol % were sufficient for reactions of many aryl chlorides and bromides. In the presence of this catalyst, aryl sulfonates also coupled with ammonia for the first time in high yields. A comparison of reactions in the presence of this catalyst versus those in the presence of existing copper and palladium systems revealed a complementary, if not broader, substrate scope. The utility of this method to generate amides, imides, and carbamates is illustrated by a one-pot synthesis of a small library of these carbonyl compounds from aryl bromides and chlorides, ammonia, and acid chlorides or anhydrides. Mechanistic studies show that reactions conducted with the combination of Pd[P(o-tol)(3)](2) and CyPF-t-Bu as catalyst occur with faster rates and higher yields than those conducted with CyPF-t-Bu and palladiun(II) as catalyst precursors because of the low concentration of active catalyst that is generated from the combination of palladium(II), ammonia, and base.

Palladium-Catalyzed Direct C-H Allylation of Electron-Deficient Polyfluoroarenes with Alkynes.

PubMed

Zheng, Jun; Breit, Bernhard

2018-04-06

A palladium-catalyzed intermolecular direct C-H allylation of polyfluoroarenes with alkynes is reported. Unlike classic hydroarylation reactions, alkynes are used as allylic electrophile surrogates in this direct aromatic C-H allylation. As an atom-economic and efficient method, various linear allylated fluoroarenes were synthesized from two simple and easy-to-access feedstocks in good to excellent yields, as well as regio- and stereoselectivity.

Palladium-Catalyzed Asymmetric Allylic Alkylation of 4-Substituted Isoxazolidin-5-ones: Straightforward Access to β2,2 -Amino Acids.

PubMed

Nascimento de Oliveira, Marllon; Arseniyadis, Stellios; Cossy, Janine

2018-04-03

We report here an unprecedented and highly enantioselective palladium-catalyzed allylic alkylation applied to 4-substituted isoxazolidin-5-ones. Ultimately, the process provides a straightforward access to β 2,2 -amino acids bearing an all-carbon quaternary stereogenic center in great yields and a high degree of enantioselectivity. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Efficient palladium-catalyzed asymmetric allylic alkylation of ketones and aldehydes.

PubMed

Zhao, Xiaohu; Liu, Delong; Xie, Fang; Liu, Yangang; Zhang, Wanbin

2011-03-21

Palladium-catalyzed asymmetric allylic alkylation of ketones, via enamines generated in situ as nucleophiles, were carried out smoothly with chiral metallocene-based P,N-ligands. Under the same conditions, however, reactions of aldehydes could hardly be observed. Subsequently, this obstacle was resolved by using chiral metallocene-based P,P-ligands. Both ketones and aldehydes afforded excellent enantioselectivities with up to 98% ee and 94% ee, respectively.

Replacing Conventional Carbon Nucleophiles with Electrophiles: Nickel-Catalyzed Reductive Alkylation of Aryl Bromides and Chlorides

PubMed Central

2012-01-01

A general method is presented for the synthesis of alkylated arenes by the chemoselective combination of two electrophilic carbons. Under the optimized conditions, a variety of aryl and vinyl bromides are reductively coupled with alkyl bromides in high yields. Under similar conditions, activated aryl chlorides can also be coupled with bromoalkanes. The protocols are highly functional-group tolerant (−OH, −NHTs, −OAc, −OTs, −OTf, −COMe, −NHBoc, −NHCbz, −CN, −SO2Me), and the reactions are assembled on the benchtop with no special precautions to exclude air or moisture. The reaction displays different chemoselectivity than conventional cross-coupling reactions, such as the Suzuki–Miyaura, Stille, and Hiyama–Denmark reactions. Substrates bearing both an electrophilic and nucleophilic carbon result in selective coupling at the electrophilic carbon (R–X) and no reaction at the nucleophilic carbon (R–[M]) for organoboron (−Bpin), organotin (−SnMe3), and organosilicon (−SiMe2OH) containing organic halides (X–R–[M]). A Hammett study showed a linear correlation of σ and σ(−) parameters with the relative rate of reaction of substituted aryl bromides with bromoalkanes. The small ρ values for these correlations (1.2–1.7) indicate that oxidative addition of the bromoarene is not the turnover-frequency determining step. The rate of reaction has a positive dependence on the concentration of alkyl bromide and catalyst, no dependence upon the amount of zinc (reducing agent), and an inverse dependence upon aryl halide concentration. These results and studies with an organic reductant (TDAE) argue against the intermediacy of organozinc reagents. PMID:22463689

Chemoselective chromium(II)-catalyzed cross-coupling reactions of dichlorinated heteroaromatics with functionalized aryl grignard reagents.

PubMed

Steib, Andreas K; Kuzmina, Olesya M; Fernandez, Sarah; Malhotra, Sushant; Knochel, Paul

2015-01-26

Chromium(II) chloride catalyzes the chemoselective cross-coupling reaction of dichloropyridines with a range of functionalized (hetero)aromatic Grignard reagents at room temperature. Functional groups, such as esters and acetals, are well tolerated in this transformation. Previously challenging substrates, quinolines and isoquinolines, participate in the selective Cr-catalyzed cross-coupling in cyclopentyl methyl ether (CPME) as the solvent. The effective purging of Cr salts is demonstrated by using various solid supports. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Antileishmanial pharmacomodulation in 8-nitroquinolin-2(1H)-one series.

PubMed

Kieffer, Charline; Cohen, Anita; Verhaeghe, Pierre; Paloque, Lucie; Hutter, Sébastien; Castera-Ducros, Caroline; Laget, Michèle; Rault, Sylvain; Valentin, Alexis; Rathelot, Pascal; Azas, Nadine; Vanelle, Patrice

2015-05-15

An antileishmanial pharmacomodulation at position 4 of 8-nitroquinolin-2(1H)-one was conducted by using the Sonogashira and Suzuki-Miyaura coupling reactions. A series of 25 derivatives was tested in vitro on the promastigote stage of Leishmania donovani along with an in vitro cytotoxicity evaluation on the human HepG2 cell line. Only the derivatives bearing a phenyl moiety at position 4 of the quinoline ring displayed interesting biologic profile, when the phenyl moiety was substituted at the para position by a Br or Cl atom, or by a CF3 group. Among them, molecules 17 and 19 were the most selective and were then tested in vitro on the intracellular amastigote stage of both L. donovani and Leishmania infantum, in parallel with complementary in vitro cytotoxicity assays on the macrophage cell lines THP-1 and J774A.1. Molecule 19 showed no activity on the amastigote stages of the parasites and some cytotoxicity on the J774A.1 cell line while molecule 17, less cytotoxic than 19, showed anti-amastigote activity in L. infantum, being 3 times less active than miltefosine but more active and selective than pentamidine. Nevertheless, hit-molecule 17 did not appear as selective as the parent compound. Copyright © 2015 Elsevier Ltd. All rights reserved.

Palladium-catalyzed heteroannulation of 1,3-dienes to form alpha-alkylidene-gamma-butyrolactones.

PubMed

Gagnier, S V; Larock, R C

2000-03-10

alpha-Alkylidene-gamma-butyrolactones are readily prepared by the palladium-catalyzed heteroannulation of a variety of 1,3-dienes by alpha-iodo and alpha-bromo acrylic acids. The best results are obtained by employing a catalytic amount of the sterically hindered chelating alkyl phosphine D-t-BPF [(di-tert-butylphosphino)ferrocene]. In most cases, this process is highly regioselective. The reaction is believed to proceed via (1) oxidative addition of the vinylic halide to Pd(0), (2) organopalladium addition to the less hindered end of the 1,3-diene to form a pi-allylpalladium intermediate, and (3) nucleophilic displacement of the palladium by the carboxylate ion.

Synthesis of pyrrole-imidazole polyamide oligomers based on a copper-catalyzed cross-coupling strategy.

PubMed

Shiga, Naoki; Takayanagi, Shihori; Muramoto, Risa; Murakami, Tasuku; Qin, Rui; Suzuki, Yuta; Shinohara, Ken-Ichi; Kaneda, Atsushi; Nemoto, Tetsuhiro

2017-05-15

Pyrrole-imidazole (Py-Im) polyamides are useful tools for chemical biology and medicinal chemistry studies due to their unique binding properties to the minor groove of DNA. We developed a novel method of synthesizing Py-Im polyamide oligomers based on a Cu-catalyzed cross-coupling strategy. All four patterns of dimer fragments could be synthesized using a Cu-catalyzed Ullmann-type cross-coupling with easily prepared monomer units. Moreover, we demonstrated that pyrrole dimer, trimer, and tetramer building blocks for Py-Im polyamide synthesis were accessible by combining site selective iodination of the pyrrole/pyrrole coupling adduct. Copyright © 2017 Elsevier Ltd. All rights reserved.

Synthesis, characterization, and catalytic activity in Suzuki coupling and catalase-like reactions of new chitosan supported Pd catalyst.

PubMed

Baran, Talat; Inanan, Tülden; Menteş, Ayfer

2016-07-10

The aim of this study is to analyze the synthesis of a new chitosan supported Pd catalyst and examination of its catalytic activity in: Pd catalyst was synthesized using chitosan as a biomaterial and characterized with FTIR, TG/DTG, XRD, (1)H NMR, (13)C NMR, SEM-EDAX, ICP-OES, Uv-vis spectroscopies, and magnetic moment, along with molar conductivity analysis. Biomaterial supported Pd catalyst indicated high activity and long life time as well as excellent turnover number (TON) and turnover frequency (TOF) values in Suzuki reaction. Biomaterial supported Pd catalyst catalyzed H2O2 decomposition reaction with considerable high activity using comparatively small loading catalyst (10mg). Redox potential of biomaterial supported Pd catalyst was still high without negligible loss (13% decrease) after 10 cycles in reusability tests. As a consequence, eco-friendly biomaterial supported Pd catalyst has superior properties such as high thermal stability, long life time, easy removal from reaction mixture and durability to air, moisture and high temperature. Copyright © 2016 Elsevier Ltd. All rights reserved.

Palladium-catalyzed one-pot three- or four-component coupling of aryl iodides, alkynes, and amines through C-N bond cleavage: efficient synthesis of indole derivatives.

PubMed

Hao, Wei; Geng, Weizhi; Zhang, Wen-Xiong; Xi, Zhenfeng

2014-02-24

An efficient synthesis of N-substituted indole derivatives was realized by combining the Pd-catalyzed one-pot multicomponent coupling approach with cleavage of the C(sp(3))-N bonds. Three or four components of aryl iodides, alkynes, and amines were involved in this coupling process. The cyclopentadiene-phosphine ligand showed high efficiency. A variety of aryl iodides, including cyclic and acyclic tertiary amino aryl iodides, and substituted 1-bromo-2-iodobenzene derivatives could be used. Both symmetric and unsymmetric alkynes substituted with alkyl, aryl, or trimethylsilyl groups could be applied. Cyclic secondary amines such as piperidine, morpholine, 4-methylpiperidine, 1-methylpiperazine, 2-methylpiperidine, and acyclic amines including secondary and primary amines all showed good reactivity. Further application of the resulting indole derivatives was demonstrated by the synthesis of benzosilolo[2,3-b]indole. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Synthesis of substituted isoquinolines utilizing palladium-catalyzed α-arylation of ketones

PubMed Central

Donohoe, Timothy J.; Pilgrim, Ben S.; Jones, Geraint R.; Bassuto, José A.

2012-01-01

The utilization of sequential palladium-catalyzed α-arylation and cyclization reactions provides a general approach to an array of isoquinolines and their corresponding N-oxides. This methodology allows the convergent combination of readily available precursors in a regioselective manner and in excellent overall yields. This powerful route to polysubstituted isoquinolines, which is not limited to electron rich moieties, also allows rapid access to analogues of biologically active compounds. PMID:22753504

A Divergent Mechanistic Course of Pd(0)-Catalyzed Aza-Claisen Rearrangement and Aza-Rautenstrauch-Type Cyclization of N-Allyl-Ynamides

PubMed Central

DeKorver, Kyle A.; Hsung, Richard P.; Lohse, Andrew G.; Zhang, Yu

2010-01-01

A fascinating mechanistic study of ynamido-palladium-π-allyl complexes is described that features isolation of a unique silyl-ketenimine via aza-Claisen rearrangement, which can be accompanied by an unusual thermal N-to-C 1,3-Ts shift in the formation of tertiary nitriles, and a novel cyclopentenimine formation via a palladium catalyzed aza-Rautenstrauch-type cyclization pathway. PMID:20337418

Linear scaling relationships and volcano plots in homogeneous catalysis - revisiting the Suzuki reaction.

PubMed

Busch, Michael; Wodrich, Matthew D; Corminboeuf, Clémence

2015-12-01

Linear free energy scaling relationships and volcano plots are common tools used to identify potential heterogeneous catalysts for myriad applications. Despite the striking simplicity and predictive power of volcano plots, they remain unknown in homogeneous catalysis. Here, we construct volcano plots to analyze a prototypical reaction from homogeneous catalysis, the Suzuki cross-coupling of olefins. Volcano plots succeed both in discriminating amongst different catalysts and reproducing experimentally known trends, which serves as validation of the model for this proof-of-principle example. These findings indicate that the combination of linear scaling relationships and volcano plots could serve as a valuable methodology for identifying homogeneous catalysts possessing a desired activity through a priori computational screening.

Dinuclear NHC-palladium complexes containing phosphine spacers: synthesis, X-ray structures and their catalytic activities towards the Hiyama coupling reaction.

PubMed

Yang, Jin; Li, Pinhua; Zhang, Yicheng; Wang, Lei

2014-05-21

Six dinuclear N-heterocyclic carbene (NHC) palladium complexes, [PdCl2(IMes)]2(μ-dppe) (1), [PdCl2(IPr)]2(μ-dppe) (2), [PdCl2(IMes)]2(μ-dppb) (3), [PdCl2(IPr)]2(μ-dppb) (4), [PdCl2(IMes)]2(μ-dpph) (5), and [PdCl2(IPr)]2(μ-dpph) (6) [IMes = N,N'-bis-(2,4,6-trimethylphenyl)imidazol-2-ylidene; IPr = N,N'-bis-(2,6-di(iso-propyl)phenyl)imidazol-2-ylidene; dppe = 1,2-bis(diphenylphosphino)ethane, dppb = 1,4-bis(diphenylphosphino)butane; and dpph = 1,6-bis(diphenylphosphino)hexane], have been synthesized through bridge-cleavage reactions of chloro-bridged dimeric compounds, [Pd(μ-Cl)(Cl)(NHC)]2, with the corresponding diphosphine ligands. The obtained compounds were fully characterized by (1)H NMR, (13)C NMR and (31)P NMR spectroscopy, FT-IR, elemental analysis and single-crystal X-ray crystallography. Moreover, further explorations of the catalytic potential of the dinuclear carbene palladium complexes as catalysts for the Pd-catalyzed transformations have been performed under microwave irradiation conditions, and the complexes exhibited moderate to good catalytic activity in the Hiyama coupling reaction of trimethoxyphenylsilane with aryl chlorides.

Tandem reactions initiated by copper-catalyzed cross-coupling: a new strategy towards heterocycle synthesis.

PubMed

Liu, Yunyun; Wan, Jie-Ping

2011-10-21

Copper-catalyzed cross-coupling reactions which lead to the formation of C-N, C-O, C-S and C-C bonds have been recognized as one of the most useful strategies in synthetic organic chemistry. During past decades, important breakthroughs in the study of Cu-catalyzed coupling processes demonstrated that Cu-catalyzed reactions are broadly applicable to a variety of research fields related to organic synthesis. Representatively, employing these coupling transformations as key steps, a large number of tandem reactions have been developed for the construction of various heterocyclic compounds. These tactics share the advantages of high atom economics of tandem reactions as well as the broad tolerance of Cu-catalyst systems. Therefore, Cu-catalyzed C-X (X = N, O, S, C) coupling transformation-initiated tandem reactions were quickly recognized as a strategy with great potential for synthesizing heterocyclic compounds and gained worldwide attention. In this review, recent research progress in heterocycle syntheses using tandem reactions initiated by copper-catalyzed coupling transformations, including C-N, C-O, C-S as well as C-C coupling processes are summarized.

A new family of nucleophiles for photoinduced, copper-catalyzed cross-couplings via single-electron transfer: reactions of thiols with aryl halides under mild conditions (O °C).

PubMed

Uyeda, Christopher; Tan, Yichen; Fu, Gregory C; Peters, Jonas C

2013-06-26

Building on the known photophysical properties of well-defined copper-carbazolide complexes, we have recently described photoinduced, copper-catalyzed N-arylations and N-alkylations of carbazoles. Until now, there have been no examples of the use of other families of heteroatom nucleophiles in such photoinduced processes. Herein, we report a versatile photoinduced, copper-catalyzed method for coupling aryl thiols with aryl halides, wherein a single set of reaction conditions, using inexpensive CuI as a precatalyst without the need for an added ligand, is effective for a wide range of coupling partners. As far as we are aware, copper-catalyzed C-S cross-couplings at 0 °C have not previously been achieved, which renders our observation of efficient reaction of an unactivated aryl iodide at -40 °C especially striking. Mechanistic investigations are consistent with these photoinduced C-S cross-couplings following a SET/radical pathway for C-X bond cleavage (via a Cu(I)-thiolate), which contrasts with nonphotoinduced, copper-catalyzed processes wherein a concerted mechanism is believed to occur.

Amide to Alkyne Interconversion via a Nickel/Copper-Catalyzed Deamidative Cross-Coupling of Aryl and Alkenyl Amides.

PubMed

Srimontree, Watchara; Chatupheeraphat, Adisak; Liao, Hsuan-Hung; Rueping, Magnus

2017-06-16

A nickel-catalyzed deamidative cross-coupling reaction of amides with terminal alkynes as coupling partners was disclosed. This newly developed methodology allows the direct interconversion of amides to alkynes and enables a facile route for C(sp2)-C(sp) bond formation in a straightforward and mild fashion.

Zinc-Catalyzed Synthesis of Conjugated Dienoates through Unusual Cross-Couplings of Zinc Carbenes with Diazo Compounds.

PubMed

Mata, Sergio; González, María J; González, Jesús; López, Luis A; Vicente, Rubén

2017-01-23

Zinc-catalyzed selective cross-coupling of two carbene sources, such as vinyl diazo compounds and enynones, enabled the synthesis of conjugated dienoate derivatives. This reaction involved the unprecedented coupling of a zinc furyl carbene with vinyl diazo compounds through the γ-carbon. Alternatively, dienoates were also prepared by a commutative cross-coupling of zinc vinyl carbenes generated from cyclopropenes and simple diazo compounds. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Park Y. S.; Kale, T.; Wu, Q.

A series of diketopyrrolopyrrole(DPP)-based small molecules have been synthesized by palladium-catalyzed coupling reactions. Electron-donating moieties (benzothiophene, benzoselenophene, and benzotellurophene) are bridged by an electron-withdrawing DPP unit to generate donor-acceptor-donor (D-A-D) type molecules. We observe red-shifts in absorption spectra of these compounds by varying heteroatoms from sulfur to tellurium. In bulk heterojunction solar cells with [6,6]phenyl-C61-butyric acid methyl ester (PC61BM) as acceptor, we obtain power conversion efficiencies of 2.4% (benzothiophene), 4.1% (benzoselenophene), and 3.0% (benzotellurophene), respectively.

CH functionalization of heteroaromatic compounds by transition metal catalysis

NASA Astrophysics Data System (ADS)

Tanba, Shunsuke; Fujiwara, Taiki; Monguchi, Daiki; Mori, Atsunori

2010-06-01

Transition metal-catalyzed CH functioanlization of thiazoles and thiophenes are carried out. The reaction of thiophene with aryl halide in the presence of a palladium catalyst underwent the CC bond forming reaction at the CH bond of thiophene. By employing the reaction head-to-tail-type oligothiophene is synthesized in a stepwise manner. When several azoles are treated with secondary amines and amides in the presence of a copper catalyst, oxidative CH-NH coupling took place to form the carbon-nitrogen bond.

One-pot synthesis of 4,8-dibromobenzo[1,2-c;4,5-c']bis[1,2,5]thiadiazole.

PubMed

Tam, Teck Lip; Li, Hairong; Wei, Fengxia; Tan, Ke Jie; Kloc, Christian; Lam, Yeng Ming; Mhaisalkar, Subodh G; Grimsdale, Andrew C

2010-08-06

A one-step synthesis of 4,8-dibromobenzo[1,2-c;4,5-c']bis[1,2,5]thiadiazole with use of 1,2,4,5-tetraaminobenzene tetrahydrobromide and thionyl bromide in good yield is reported. This unit can then be used in the synthesis of low bandgap materials via palladium-catalyzed coupling reactions. The approach offers a quick and easy way to prepare low bandgap materials as compared to the current literature methods.

Iron-Catalyzed C-O Bond Activation: Opportunity for Sustainable Catalysis.

PubMed

Bisz, Elwira; Szostak, Michal

2017-10-23

Oxygen-based electrophiles have emerged as some of the most valuable cross-coupling partners in organic synthesis due to several major strategic and environmental benefits, such as abundance and potential to avoid toxic halide waste. In this context, iron-catalyzed C-O activation/cross-coupling holds particular promise to achieve sustainable catalytic protocols due to its natural abundance, inherent low toxicity, and excellent economic and ecological profile. Recently, tremendous progress has been achieved in the development of new methods for functional-group-tolerant iron-catalyzed cross-coupling reactions by selective C-O cleavage. These methods establish highly attractive alternatives to traditional cross-coupling reactions by using halides as electrophilic partners. In particular, new easily accessible oxygen-based electrophiles have emerged as substrates in iron-catalyzed cross-coupling reactions, which significantly broaden the scope of this catalysis platform. New mechanistic manifolds involving iron catalysis have been established; thus opening up vistas for the development of a wide range of unprecedented reactions. The synthetic potential of this sustainable mode of reactivity has been highlighted by the development of new strategies in the construction of complex motifs, including in target synthesis. The most recent advances in sustainable iron-catalyzed cross-coupling of C-O-based electrophiles are reviewed, with a focus on both mechanistic aspects and synthetic utility. It should be noted that this catalytic manifold provides access to motifs that are often not easily available by other methods, such as the assembly of stereodefined dienes or C(sp 2 )-C(sp 3 ) cross-couplings, thus emphasizing the synthetic importance of this mode of reactivity. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Biosynthesis of palladium nanoparticles by using Moringa oleifera flower extract and their catalytic and biological properties.

PubMed

Anand, K; Tiloke, C; Phulukdaree, A; Ranjan, B; Chuturgoon, A; Singh, S; Gengan, R M

2016-12-01

The biosynthesis of nanostructured biopalladium nanoparticles (PdNPs) from an aqueous solution of crystalline palladium acetate is reported. For the synthesised PdNPs in solution, an agroforest biomass waste petal of Moringa oleifera derived bis-phthalate was used as natural reducing and biocapping agents. Continuous absorption in the UV region and subsequent brown colour change confirmed the formation of PdNPs. A strong surface plasmon peak for PdNPs occurred at 460nm. PdNPs were characterized by SEM with EDX, FTIR, TEM and DLS. The chemical composition of the aqueous extract was determined by GC-MS coupled with FTIR and 1 NMR. The catalytic degradation effect by PdNPs on industrial organic toxic effluents p-nitrophenol (PNP) and methylene blue dye was monitored by UV Spectroscopy. On the other hand PdNPs catalysed the base mediated suzuki coupling reaction for biphenyl synthesis, in water. Moreover, PdNPs were found to be reusable catalysts. Toxicity studies of PdNPs showed that the death of brine shrimp to be <50%. Therefore, PdNPs displayed potential for further anticancer studies via tumour cell lines. The in vitro cytotoxicity evaluation of the extract capped nanoparticles was carried out using human lung carcinoma cells (A549) and peripheral lymphocytes normal cells by MTT cell viability assay. Also, PdNPs showed antibacterial activity against Enterococcus faecalis among the different tested strains, including Bacillus cereus, Staphylococcus aureus, Esherichia coli and Candida albicans, Candida utilis. Copyright © 2016 Elsevier B.V. All rights reserved.

Concise synthesis of the hasubanan alkaloid (±)-cepharatine A using a Suzuki coupling reaction to effect o,p-phenolic coupling.

PubMed

Magnus, Philip; Seipp, Charles

2013-09-20

Suzuki coupling of 10 and 11 resulted in 9, which was O-alkylated to provide 12. Treatment of 12 with CsF in DMF resulted in the formation of the completed core structure 13 in a single step. Reductive amination of 13 completed the synthesis of (±)-cepharatine A, 4.

Synthesis of phenanthridinones from N-methoxybenzamides and arenes by multiple palladium-catalyzed C-H activation steps at room temperature.

PubMed

Karthikeyan, Jaganathan; Cheng, Chien-Hong

2011-10-10

Many steps make light work: substituted phenanthridinones can be obtained with high regioselectivity and in very good yields by palladium-catalyzed cyclization reactions of N-methoxybenzamides with arenes. The reaction proceeds through multiple oxidative C-H activation and C-C/C-N formation steps in one pot at room temperature, and thus provides a simple method for generating bioactive phenanthridinones. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

New synthesis of artepillin C, a prenylated phenol, utilizing lipase-catalyzed regioselective deacetylation as the key step.

PubMed

Yashiro, Kazuki; Hanaya, Kengo; Shoji, Mitsuru; Sugai, Takeshi

2015-01-01

We have synthesized artepillin C, a diprenylated p-hydroxycinnamate originally isolated from Brazilian propolis and exhibiting antioxidant and antitumor activities, from 2,6-diallylphenol. Replacement of the terminal vinyl with 2,2-dimethylvinyl group by olefin cross-metathesis and subsequent transformation yielded 2,6-diprenyl-1,4-hydroquinone diacetate. Candida antarctica lipase B-catalyzed deacetylation in 2-propanol regioselectively removed the less hindered acetyl group to give 2,6-diprenyl-1,4-hydroquinone 1-monoacetate. After triflation of the liberated 4-hydroxy group, a three-carbon side chain was introduced by palladium-mediated alkenylation with methyl acrylate. Final hydrolysis of the esters furnished artepillin C.

Evolution of a Fourth Generation Catalyst for the Amination and Thioetherification of Aryl Halides

PubMed Central

Hartwig, John F.

2010-01-01

Conspectus Synthetic methods to form the carbon-nitrogen bonds in aromatic amines are fundamental enough to be considered part of introductory organic courses. Arylamines are important because they are common precursors to or substructures within active pharmaceutical ingredients and herbicides produced on ton scales, as well as conducting polymers and layers of organic light-emitting diodes produced on small scale. For many years, this class of compound was prepared from classical methods, such as nitration, reduction and reductive alkylation, copper-mediated chemistry at high temperatures, addition to benzyne intermediates, or direct nucleophilic substitution on particularly electron-poor aromatic or heteroaromatic halides. During the past decade, these methods to form aromatic amines have been largely supplanted by palladium-catalyzed coupling reactions of amines with aryl halides. The scope and efficiency of the palladium-catalyzed processes has gradually improved with successive generations of catalysts to the point of being useful for the synthesis of both milligrams and kilograms of product. This Account describes the conceptual basis and utility of our latest, “fourth-generation” catalyst for the coupling of amines and related reagents with aryl halides. The introductory sections of this account describe the progression of catalyst development from the first-generation to current systems and the motivation for selection of the components of the fourth-generation catalyst. This progression began with catalysts containing palladium and sterically hindered monodentate aromatic phosphines used initially for coupling of tin amides with haloarenes in the first work on C-N coupling. A second generation of catalysts was then developed based on the combination of palladium and aromatic bisphosphines. These systems were then followed by third-generation systems catalysts on the combination of palladium and a sterically hindered alkylmonophosphine or N-heterocyclic carbene. During the past five years, we have studied a fourth-generation catalyst for these reactions containing ligands that combine the chelating properties of the second-generation systems with the steric hindrance and strong electron donation of the third-generation systems. This combination has created a catalyst that couples aryl chlorides, bromides and iodides with primary amines, N-H imines, and hydrazones in high yield, with broad scope, high functional group tolerance, nearly perfect selectivity for monoarylation, and the lowest levels of palladium that have been used for C-N coupling. This catalyst is based on palladium and a sterically hindered version of the Josiphos family of ligands that possesses a ferrocenyl-1-ethylbackbone, a hindered di-tert-butylphosphino group, and a hindered dicyclohexylphosphino group. This latest generation of catalyst not only improves the coupling of primary amines and related nucleophiles, but it has dramatically improved the coupling of thiols with haloarenes to form C-S bonds. This catalyst system couples both aliphatic and aromatic thiols with chloroarenes with much greater scope, functional group tolerance, and turnover numbers than had been observed previously. The effects of structural features of the Josiphos ligand on catalyst activity have been revealed by examining the reactivity of catalysts generated from ligands lacking one or more of the structural elements of the most active catalyst. These modified ligands lack the relative stereochemistry of the ferrocenyl-1-ethyl backbone, the strong electron donation of the dialkylphosphino groups, the steric demands of the alkylphosphine groups, or the stability of the ferrocenyl unit. This set of studies showed that each one of these structural features contributed to the high reactivity and selectivity of the catalyst containing the hindered, bidentate Josiphos ligand. Finally, a series of studies on the effect of electronic properties on the rates of reductive elimination have recently distinguished between the effect of the properties of the M-N σ-bond and the nitrogen electron pair on the rate of reductive elimination. These studies have shown that the effect of substituents attached to the metal-bound nitrogen or carbon atoms on the rate of reductive elimination are similar. Because the amido ligands contain an electron pair, while the alkyl ligands do not, we have concluded that the major electronic effect is transmitted through the σ-bond. In other words, we have concluded that the electronic effect on the metal-nitrogen σ bond dominates an electronic effect on the nitrogen electron pair. PMID:18681463

Mild Aromatic Palladium-Catalyzed Protodecarboxylation: Kinetic Assessment of the Decarboxylative Palladation and the Protodepalladation Steps

PubMed Central

Dickstein, Joshua S.; Curto, John M.; Gutierrez, Osvaldo; Mulrooney, Carol A.; Kozlowski, Marisa C.

2013-01-01

Mechanism studies of a mild palladium catalyzed decarboxylation of aromatic carboxylic acids are described. In particular, reaction orders and activation parameters for the two stages of the transformation were determined. These studies guided development of a catalytic system capable of turnover. Further evidence reinforces that the second stage, protonation of the aryl palladium intermediate, is the rate-determining step of the reaction. The first step, decarboxylative palladation is proposed to occur through an intramolecular electrophilic palladation pathway, which is supported by computational and mechansim studies. In contrast to the reverse reaction (C-H insertion), the data support an electrophilic aromatic substitution mechanism involving a stepwise intramolecular protonation sequence for the protodepalladation portion of the reaction. PMID:23590518

Pd-Catalyzed Cross-Coupling Reactions of Amides and Aryl Mesylates

PubMed Central

Dooleweerdt, Karin; Fors, Brett P.; Buchwald, Stephen L.

2010-01-01

A catalyst, based on a biarylphosphine ligand, for the Pd-catalyzed cross-coupling reactions of amides and aryl mesylates is described. This system allows an array of aryl and heteroaryl mesylates to be transformed into the corresponding N-arylamides in moderate to excellent yields. PMID:20420379

Cross-coupling of alkenyl/aryl carboxylates with Grignard reagent via Fe-catalyzed C-O bond activation.

PubMed

Li, Bi-Jie; Xu, Li; Wu, Zhen-Hua; Guan, Bing-Tao; Sun, Chang-Liang; Wang, Bi-Qin; Shi, Zhang-Jie

2009-10-21

Iron-catalyzed cross-coupling of alkenyl/aryl carboxylates with primary alkyl Grignard reagent was described. This reaction brought a new family of electrophiles to iron catalysis. The combination of an inexpensive carboxylate electrophile and an iron catalyst would generate ample advantages.

Palladium Catalyzed Reduction of Nitrobenzene.

ERIC Educational Resources Information Center

Mangravite, John A.

1983-01-01

Compares two palladium (Pd/C) reducing systems to iron/tin-hydrochloric acid (Fe/HCl and Sn/HCl) reductions and suggests an efficient, clean, and inexpensive procedures for the conversion of nitrobenzene to aniline. Includes laboratory procedures used and discussion of typical results obtained. (JN)

First application of an efficient and versatile ligand for copper-catalyzed cross-coupling reactions of vinyl halides with N-heterocycles and phenols.

PubMed

Kabir, M Shahjahan; Lorenz, Michael; Namjoshi, Ojas A; Cook, James M

2010-02-05

2-Pyridin-2-yl-1H-benzoimidazole L3 is presented as a new, efficient, and versatile bidentate N-donor ligand suitable for the copper-catalyzed formation of vinyl C-N and C-O bonds. This inexpensive and easily prepared ligand facilitates copper-catalyzed cross-coupling reactions of alkenyl bromides and iodides with N-heterocycles and phenols to afford the desired cross-coupled products in good to excellent yields with full retention of stereochemistry. This method is particularly noteworthy given its efficiency, that is, mild reaction conditions, low catalyst loading, simplicity, versatility, and exceptional level of functional group tolerance.

First Application of An Efficient and Versatile Ligand for Copper-Catalyzed Cross-Coupling Reactions of Vinyl Halides with N-Heterocycles and Phenols

PubMed Central

Kabir, M. Shahjahan; Lorenz, Michael; Namjoshi, Ojas A.; Cook, James M.

2010-01-01

2-Pyridin-2-yl-1H-benzoimidazole L3 is presented as a new, efficient, and versatile bidentate N-donor ligand suitable for the copper-catalyzed formation of vinyl C-N and C-O bonds. This inexpensive and easily prepared ligand facilitates copper-catalyzed cross-coupling reactions of alkenyl bromides and iodides with N-heterocycles and phenols to afford the desired cross-coupled products in good to excellent yields with full retention of stereochemistry. This method is particularly noteworthy given its efficiency i.e., mild reaction conditions, low catalyst loading, simplicity, versatility, and exceptional level of functional group tolerance. PMID:20039699

Ligand- and base-free copper(II)-catalyzed C-N bond formation: cross-coupling reactions of organoboron compounds with aliphatic amines and anilines.

PubMed

Quach, Tan D; Batey, Robert A

2003-11-13

[reaction: see text] A ligandless and base-free Cu-catalyzed protocol for the cross-coupling of arylboronic acids and potassium aryltrifluoroborate salts with primary and secondary aliphatic amines and anilines is described. The process utilizes catalytic copper(II) acetate monohydrate and 4 A molecular sieves in dichloromethane at slightly elevated temperatures under an atmosphere of oxygen. A broad range of functional groups are tolerated on both of the cross-coupling partners.

Structuring Pd Nanoparticles on 2H-WS2 Nanosheets Induces Excellent Photocatalytic Activity for Cross-Coupling Reactions under Visible Light.

PubMed

Raza, Faizan; Yim, DaBin; Park, Jung Hyun; Kim, Hye-In; Jeon, Su-Ji; Kim, Jong-Ho

2017-10-18

Effective photocatalysts and their surface engineering are essential for the efficient conversion of solar energy into chemical energy in photocatalyzed organic transformations. Herein, we report an effective approach for structuring Pd nanoparticles (NPs) on exfoliated 2H-WS 2 nanosheets (WS 2 /PdNPs), resulting in hybrids with extraordinary photocatalytic activity in Suzuki reactions under visible light. Pd NPs of different sizes and densities, which can modulate the photocatalytic activity of the as-prepared WS 2 /PdNPs, were effectively structured on the basal plane of 2H-WS 2 nanosheets via a sonic wave-assisted nucleation method without any reductants at room temperature. As the size of Pd NPs on WS 2 /PdNPs increased, their photocatalytic activity in Suzuki reactions at room temperature increased substantially. In addition, it was found that protic organic solvents play a crucial role in activating WS 2 /PdNPs catalysts in photocatalyzed Suzuki reactions, although these solvents are generally considered much less effective than polar aprotic ones in the conventional Suzuki reactions promoted by heterogeneous Pd catalysts. A mechanistic investigation suggested that photogenerated holes are transferred to protic organic solvents, whereas photogenerated electrons are transferred to Pd NPs. This transfer makes the Pd NPs electron-rich and accelerates the rate-determining step, i.e., the oxidative addition of aryl halides under visible light. WS 2 /PdNPs showed the highest turnover frequency (1244 h -1 ) for photocatalyzed Suzuki reactions among previously reported photocatalysts.

Highly enantioselective synthesis of γ-, δ-, and ε-chiral 1-alkanols via Zr-catalyzed asymmetric carboalumination of alkenes (ZACA)–Cu- or Pd-catalyzed cross-coupling

PubMed Central

Xu, Shiqing; Oda, Akimichi; Kamada, Hirofumi; Negishi, Ei-ichi

2014-01-01

Despite recent advances of asymmetric synthesis, the preparation of enantiomerically pure (≥99% ee) compounds remains a challenge in modern organic chemistry. We report here a strategy for a highly enantioselective (≥99% ee) and catalytic synthesis of various γ- and more-remotely chiral alcohols from terminal alkenes via Zr-catalyzed asymmetric carboalumination of alkenes (ZACA reaction)–Cu- or Pd-catalyzed cross-coupling. ZACA–in situ oxidation of tert-butyldimethylsilyl (TBS)-protected ω-alkene-1-ols produced both (R)- and (S)-α,ω-dioxyfunctional intermediates (3) in 80–88% ee, which were readily purified to the ≥99% ee level by lipase-catalyzed acetylation through exploitation of their high selectivity factors. These α,ω-dioxyfunctional intermediates serve as versatile synthons for the construction of various chiral compounds. Their subsequent Cu-catalyzed cross-coupling with various alkyl (primary, secondary, tertiary, cyclic) Grignard reagents and Pd-catalyzed cross-coupling with aryl and alkenyl halides proceeded smoothly with essentially complete retention of stereochemical configuration to produce a wide variety of γ-, δ-, and ε-chiral 1-alkanols of ≥99% ee. The MαNP ester analysis has been applied to the determination of the enantiomeric purities of δ- and ε-chiral primary alkanols, which sheds light on the relatively undeveloped area of determination of enantiomeric purity and/or absolute configuration of remotely chiral primary alcohols. PMID:24912191

Cu-catalyzed cross-coupling reactions of epoxides with organoboron compounds.

PubMed

Lu, Xiao-Yu; Yang, Chu-Ting; Liu, Jing-Hui; Zhang, Zheng-Qi; Lu, Xi; Lou, Xin; Xiao, Bin; Fu, Yao

2015-02-11

A copper-catalyzed cross-coupling reaction of epoxides with arylboronates is described. This reaction is not limited to aromatic epoxides, because aliphatic epoxides are also suitable substrates. In addition, N-sulfonyl aziridines can be successfully converted into the products. This reaction provides convenient access to β-phenethyl alcohols, which are valuable synthetic intermediates.

Iron-catalyzed cross-coupling of N-heterocyclic chlorides and bromides with arylmagnesium reagents.

PubMed

Kuzmina, Olesya M; Steib, Andreas K; Flubacher, Dietmar; Knochel, Paul

2012-09-21

A simple, practical iron salt catalyzed procedure allows fast cross-couplings of N-heterocyclic chlorides and bromides with various electron-rich and -poor arylmagnesium reagents. A solvent mixture of THF and tBuOMe is found to be essential for achieving high yields mainly by avoiding homocoupling side reactions.

Probing the evolution of palladium species in Pd@MOF catalysts during the Heck coupling reaction: An operando X-ray absorption spectroscopy study.

PubMed

Yuan, Ning; Pascanu, Vlad; Huang, Zhehao; Valiente, Alejandro; Heidenreich, Niclas; Leubner, Sebastian; Inge, A Ken; Gaar, Jakob; Stock, Norbert; Persson, Ingmar; Martin-Matute, Belen; Zou, Xiaodong

2018-06-11

The mechanism of the Heck C-C coupling reaction catalyzed by Pd@MOFs has been investigated using operando X-ray absorption spectroscopy (XAS) and powder X-ray diffraction (PXRD) combined with transmission electron microscopy (TEM) analysis and nuclear magnetic resonance ( 1 H NMR) kinetic studies. A custom-made reaction cell was used allowing operando PXRD and XAS data collection using high-energy synchrotron radiation. By analyzing the XAS data in combination with ex situ studies, the evolution of the palladium species is followed from the as-synthesized to its deactivated form. An adaptive reaction mechanism is pro-posed. Mononuclear Pd(II) complexes are found to be the dominant active species at the beginning of the reaction, which then gradually transform into Pd nanoclusters with 13-20 Pd atoms on average in later catalytic turnovers. Consumption of available reagent and substrate leads to coordination of Cl - ions to their surfaces, which causes the poisoning of the active sites. By understanding the deactivation process, it was possible to tune the reaction conditions and prolong the lifetime of the catalyst.

Mild Palladium Catalyzed ortho C-H Bond Functionalizations of Aniline Derivatives.

PubMed

Tischler, Ms Orsolya; Tóth, Mr Balázs; Novák, Zoltán

2017-02-01

This account collects the developments and transformations which avoid the utilization of harsh reaction conditions in the field of palladium catalyzed, ortho-directed C-H activation of aniline derivatives from the first attempts to up-to-date results, including the results of our research laboratory. The discussed functionalizations performed under mild conditions include acylation, olefination, arylation, alkylation, alkoxylation reactions. Beside the optimization studies and the synthetic applications mechanistic investigations are also presented. © 2017 The Chemical Society of Japan & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Enantioselective syntheses of cryptocarya triacetate, cryptocaryolone, and cryptocaryolone diacetate.

PubMed

Smith, Catherine M; O'Doherty, George A

2003-05-29

[reaction: see text] The enantioselective syntheses of three natural products from Cryptocarya latifolia have been achieved in 13-15 steps from ethyl sorbate. The route relies upon an enantio- and regioselective Sharpless dihydroxylation and a palladium-catalyzed reduction to establish the absolute stereochemistry. The route also relies upon a highly (E)-selective olefin cross-metathesis reaction to form trans-delta-hydroxy-1-enoates. The resulting delta-hydroxy-1-enoates were subsequently converted into cryptocarya triacetate, cryptocaryolone, and cryptocaryolone diacetate.

Efficient synthesis of RITA and its analogues: derivation of analogues with improved antiproliferative activity via modulation of p53/miR-34a pathway.

PubMed

Lin, Jinshun; Jin, Xiuli; Bu, Yiwen; Cao, Deliang; Zhang, Nannan; Li, Shangfu; Sun, Qinsheng; Tan, Chunyan; Gao, Chunmei; Jiang, Yuyang

2012-12-28

A novel approach to synthesize RITA by practical palladium-catalyzed C-C bond-forming Suzuki reactions at room temperature was developed, which was used for deriving a series of substituted tricyclic α-heteroaryl (furan/thiophene) analogues of RITA under mild conditions. These novel analogues showed notable antiproliferative activity against cancer cell lines with wild-type p53 (i.e., HCT116, A549, MCF-7 and K562), but much less activity in HCT116/p53(-/-) cells. In particular, compound 1f demonstrated promising antiproliferative activity compared to RITA, with IC(50) = 28 nM in MCF-7 vs. 54 nM for RITA, and cancer cell selectivity. Compound 1f markedly activated p53 in HCT116 cells at 100 nM, triggering apoptosis. Importantly, we found that both RITA and compound 1f induced G(0)/G(1) cell cycle arrest by up-regulating miR-34a, which in turn down-regulated the expression of cell cycle-related proteins CDK4 and E2F1. In summary, this study reports an effective synthetic approach for RITA and its analogues, and elucidates a novel antiproliferative mechanism of these compounds.

A sensitive electrochemical aptasensor based on palladium nanoparticles decorated graphene-molybdenum disulfide flower-like nanocomposites and enzymatic signal amplification.

PubMed

Jing, Pei; Yi, Huayu; Xue, Shuyan; Chai, Yaqin; Yuan, Ruo; Xu, Wenju

2015-01-01

In the present study, with the aggregated advantages of graphene and molybdenum disulfide (MoS2), we prepared poly(diallyldimethylammonium chloride)-graphene/molybdenum disulfide (PDDA-G-MoS2) nanocomposites with flower-like structure, large surface area and excellent conductivity. Furthermore, an advanced sandwich-type electrochemical assay for sensitive detection of thrombin (TB) was fabricated using palladium nanoparticles decorated PDDA-G-MoS2 (PdNPs/PDDA-G-MoS2) as nanocarriers, which were functionalized by hemin/G-quadruplex, glucose oxidase (GOD), and toluidine blue (Tb) as redox probes. The signal amplification strategy was achieved as follows: Firstly, the immobilized GOD could effectively catalyze the oxidation of glucose to gluconolactone, coupling with the reduction of the dissolved oxygen to H2O2. Then, both PdNPs and hemin/G-quadruplex acting as hydrogen peroxide (HRP)-mimicking enzyme could further catalyze the reduction of H2O2, resulting in significant electrochemical signal amplification. So the proposed aptasensor showed high sensitivity with a wide dynamic linear range of 0.0001 to 40 nM and a relatively low detection limit of 0.062 pM for TB determination. The strategy showed huge potential of application in protein detection and disease diagnosis. Copyright © 2014 Elsevier B.V. All rights reserved.

Palladium-catalyzed cyclocarbonylation of o-iodoanilines with heterocumulenes: regioselective preparation of 4(3H)-quinazolinone derivatives

PubMed

Larksarp; Alper

2000-05-09

A catalyst system comprising palladium acetate-bidentate phosphine is effective for the cyclocarbonylation of o-iodoanilines with heterocumulenes at 70-100 degrees C for 12-24 h to give the corresponding 4(3H)-quinazolinone derivatives in good yields. Utilizing o-iodoaniline with isocyanates, carbodiimides, and ketenimines for the reaction, 2,4-(1H,3H)-quinazolinediones, 2-amino-4(3H)-quinazolinones and 2-alkyl-4(3H)-quinazolinones were obtained, respectively. The nature of the substrates including the electrophilicity of the carbon center of the carbodiimide, and the stability of the ketenimine, influence the product yields of this reaction. Urea-type intermediates are believed to be generated first in situ from the reaction of o-iodoanilines with heterocumulenes, followed by palladium-catalyzed carbonylation and cyclization to yield the products.

Palladium-Catalyzed Allylic C-H Bond Functionalization of Olefins

NASA Astrophysics Data System (ADS)

Liu, Guosheng; Wu, Yichen

Transition metal-mediated carbon-hydrogen bond cleavage and functionalization is a mechanistically interesting and synthetically attractive process. One of the important cases is the removal of a allylic hydrogen from an olefin by a PdII salt to yield a π-allylpalladium complex, followed by nucleophilic attack to efficient produce allylic derivatives. In contrast to the well-known allylic acetoxylation of cyclohexene, the reaction of open-chain olefins is fairly poor until recent several years. Some palladium catalytic systems have been reported to achieve allylic C-H functionalization, including acetoxylation, amination and alkylation of terminal alkenes. In the most of cases, ligand is crucial to the success of the transformation. This review surveys the recent development of palladium-catalyzed allylic C-H functionalziation of alkenes. These results promise a significant increase in the scope of olefin transformation.

Sequential rhodium/palladium catalysis: enantioselective formation of dihydroquinolinones in the presence of achiral and chiral ligands.

PubMed

Zhang, Lei; Qureshi, Zafar; Sonaglia, Lorenzo; Lautens, Mark

2014-12-08

Compatible combinations of achiral and chiral ligands can be used in rhodium/palladium catalysis to achieve highly enantioselective domino reactions. The difference in rates of catalysis and minimal effects of ligand interference confer control in the domino sequence. The "all-in-one" 1,4-conjugate arylation and C-N cross-coupling through sequential Rh/Pd catalysis provides access to enantioenriched dihydroquinolinone building blocks. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Iron-catalyzed cross-coupling of imidoyl chlorides with Grignard reagents.

PubMed

Ottesen, Lars K; Ek, Fredrik; Olsson, Roger

2006-04-27

[reaction: see text] A general, high yielding rapid iron-catalyzed cross-coupling reaction between Grignard reagents and imidoyl chlorides is described. These reactions are typically completed within 5 min, resulting in high yields of 71-96% using 5% iron catalyst in a THF-NMP solvent mixture. Functionalized imidoyl chlorides (e.g., R = CO(2)Me) gave excellent yields (89%).

Stereoselective Synthesis of Tetrasubstituted Furylalkenes via Gold-Catalyzed Cross-Coupling of Enynones with Diazo Compounds.

PubMed

Liu, Pei; Sun, Jiangtao

2017-07-07

A stereoselective, gold-catalyzed, cross-coupling reaction of enynones with diazo compounds has been developed, affording 2-alkenylfurans in moderate to good yields with excellent E-stereoselectivity. Upon using diazo compounds as nucleophiles to trap the in situ formed gold furyl carbene, this protocol provides a novel path toward the formation of unsymmetrical tetrasubstituted alkenes.

Architecture engineering toward highly active palladium integrated titanium dioxide yolk-double-shell nanoreactor for catalytic applications.

PubMed

Liu, Baocang; Wang, Qin; Yu, Shengli; Jing, Peng; Liu, Lixia; Xu, Guangran; Zhang, Jun

2014-10-21

Rational design of the hierarchical architecture of a material with well controlled functionality is crucially important for improving its properties. In this paper, we present the general strategies for rationally designing and constructing three types of hierarchical Pd integrated TiO2 double-shell architectures, i.e. yolk-double-shell TiO2 architecture (Pd@TiO2/Pd@TiO2) with yolk-type Pd nanoparticles residing inside the central cavity of the hollow TiO2 structure; ultrafine Pd nanoparticles homogenously dispersed on both the external and internal surfaces of the inner TiO2 shell; and double-shell TiO2 architecture (@TiO2/Pd@TiO2) with Pd nanoparticles solely loaded on the external surface of the inner TiO2 shell, and double-shell TiO2 architecture (@TiO2@Pd@TiO2) with Pd nanoparticles dispersed in the interlayer space of double TiO2 shells, via newly developed Pd(2+) ion-diffusion and Pd sol impregnation methodologies. These architectures are well controlled in structure, size, morphology, and configuration with Pd nanoparticles existing in various locations. Owing to the variable synergistic effects arising from the location discrepancies of Pd nanoparticle in the architectures, they exhibit remarkable variations in catalytic activity. In particular, different from previously reported yolk-shell structures, the obtained yolk-double-shell Pd@TiO2/Pd@TiO2 architecture, which is revealed for the first time, possesses a uniform hierarchical structure, narrow size distribution, and good monodispersibility, and it creates two Pd-TiO2 interfaces on the external and internal surfaces of the inner TiO2 shell, leading to the strongest synergistic effect of Pd nanoparticles with TiO2 shell. Furthermore, the interlayer chamber between the double TiO2 shells connecting with the central cavity of the hollow TiO2 structure through the mesoporous TiO2 wall forms a nanoreactor for enriching the reactants and preventing the deletion of Pd nanoparticles during the reaction, thus greatly accelerating the reaction speed. Owing to its structural features, yolk-double-shell Pd@TiO2/Pd@TiO2 architecture exhibits extremely high catalytic performance on the Suzuki-Miyaura coupling reaction. The synthetic methodologies are robust for fabricating double-shell architectures with various configurations for applications such as in catalysis, drug delivery, and medicine release. The obtained double-shell architectures may be used as novel catalyst systems with highly efficient catalytic performance for other catalytic reactions.

Synthesis of 2-Azulenyltetrathiafulvalenes by Palladium-Catalyzed Direct Arylation of 2-Chloroazulenes with Tetrathiafulvalene and Their Optical and Electrochemical Properties.

PubMed

Shoji, Taku; Araki, Takanori; Sugiyama, Shuhei; Ohta, Akira; Sekiguchi, Ryuta; Ito, Shunji; Okujima, Tetsuo; Toyota, Kozo

2017-02-03

Tetrathiafulvalene (TTF) derivatives with 2-azulenyl substituents 5-11 were prepared by the palladium-catalyzed direct arylation reaction of 2-chloroazulenes with TTF in good yield. Photophysical properties of these compounds were investigated by UV-vis spectroscopy and theoretical calculations. Redox behavior of the novel azulene-substituted TTFs was examined by using cyclic voltammetry and differential pulse voltammetry, which revealed their multistep electrochemical oxidation and/or reduction properties. Moreover, these TTF derivatives showed significant spectral change in the visible region under the redox conditions.

Palladium-catalyzed stereoretentive olefination of unactivated C(sp3)-H bonds with vinyl iodides at room temperature: synthesis of β-vinyl α-amino acids.

PubMed

Wang, Bo; Lu, Chengxi; Zhang, Shu-Yu; He, Gang; Nack, William A; Chen, Gong

2014-12-05

A method is reported for palladium-catalyzed N-quinolyl carboxamide-directed olefination of the unactivated C(sp(3))-H bonds of phthaloyl alanine with a broad range of vinyl iodides at room temperature. This reaction represents the first example of the stereoretentive installation of multisubstituted terminal and internal olefins onto unactivated C(sp(3))-H bonds. These methods enable access to a wide range of challenging β-vinyl α-amino acid products in a streamlined and controllable fashion, beginning from simple precursors.

BCl3‐Induced Annulative Oxo‐ and Thioboration for the Formation of C3‐Borylated Benzofurans and Benzothiophenes

PubMed Central

Warner, Andrew J.; Churn, Anna; McGough, John S.

2016-01-01

Abstract BCl3‐induced borylative cyclization of aryl‐alkynes possessing ortho‐EMe (E=S, O) groups represents a simple, metal‐free method for the formation of C3‐borylated benzothiophenes and benzofurans. The dichloro(heteroaryl)borane primary products can be protected to form synthetically ubiquitous pinacol boronate esters or used in situ in Suzuki–Miyaura cross couplings to generate 2,3‐disubstituted heteroarenes from simple alkyne precursors in one pot. In a number of cases alkyne trans‐haloboration occurs alongside, or instead of, borylative cyclization and the factors controlling the reaction outcome are determined. PMID:27897368

Reactions of nitroxides 15. Cinnamates bearing a nitroxyl moiety synthesized using a Mizoroki–Heck cross-coupling reaction

PubMed Central

Huras, Bogumiła

2015-01-01

Summary Cinnamic acid derivatives bearing a nitroxyl moiety (2,2,6,6-tetramethyl-1-oxyl-4-piperidyl 3-E-aryl acrylates) were synthesized in 30–100% yield using a Mizoroki–Heck cross-coupling reaction between 4-acryloyloxy-2,2,6,6-tetramethylpiperidine-1-oxyl and iodobenzene derivatives in the presence of palladium(II) acetate coordinated with a tri(o-tolyl)phosphine ligand immobilized in a polyurea matrix. PMID:26199672

1,1,1-tris(hydroxymethyl)ethane as a new, efficient, and versatile tripod ligand for copper-catalyzed cross-coupling reactions of aryl iodides with amides, thiols, and phenols.

PubMed

Chen, Yao-Jung; Chen, Hsin-Hung

2006-11-23

1,1,1-tris(hydroxymethyl)ethane was presented as a new, efficient, and versatile tridentate O-donor ligand suitable for the copper-catalyzed formation of C-N, C-S, and C-O bonds. This inexpensive and commercially available tripod ligand has been demonstrated to facilitate the copper-catalyzed cross-coupling reactions of aryl iodides with amides, thiols, and phenols to afford the corresponding desired products in good to excellent yields. [reaction: see text].

Synthesis of 4-(5-iodo-3-methylpyrazolyl) phenylsulfonamide and its elaboration to a COX II inhibitor library by solution-phase suzuki coupling using Pd/C as a solid-supported catalyst.

PubMed

Organ, Michael G; Mayer, Stanislas

2003-01-01

An effective synthesis of 4-(5-iodo-3-methylpyrazolyl) phenylsulfonamide has been developed. This aromatic iodide template served as an efficient oxidative addition partner for the preparation of a solution-phase library of Celecoxib analogues via Suzuki coupling using Pd/C, a readily filterable catalyst.

Visible-Light-Induced Nickel-Catalyzed Negishi Cross-Couplings by Exogenous-Photosensitizer-Free Photocatalysis.

PubMed

Abdiaj, Irini; Fontana, Alberto; Gomez, M Victoria; de la Hoz, Antonio; Alcázar, Jesús

2018-03-22

The merging of photoredox and transition-metal catalysis has become one of the most attractive approaches for carbon-carbon bond formation. Such reactions require the use of two organo-transition-metal species, one of which acts as a photosensitizer and the other one as a cross-coupling catalyst. We report herein an exogenous-photosensitizer-free photocatalytic process for the formation of carbon-carbon bonds by direct acceleration of the well-known nickel-catalyzed Negishi cross-coupling that is based on the use of two naturally abundant metals. This finding will open new avenues in cross-coupling chemistry that involve the direct visible-light absorption of organometallic catalytic complexes. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Stereospecific Nickel-Catalyzed Cross-Coupling Reactions of Alkyl Grignard Reagents and Identification of Selective Anti-Breast Cancer Agents**

PubMed Central

Osborne, Charlotte A.; Moore, Curtis E.; Morrissette, Naomi S.; Jarvo, Elizabeth R.

2014-01-01

β-Hydrogen-containing alkyl Grignard reagents were used in a stereospecific nickel-catalyzed cross-coupling reaction to form sp3–sp3 carbon–carbon bonds. Aryl Grignard reagents were also utilized to synthesize 1,1-diarylalkanes. Several compounds synthesized by this method exhibited selective inhibition of proliferation of MCF-7 breast cancer cells. PMID:24478275

Copper-Catalyzed Cyclopropanol Ring Opening Csp(3)-Csp(3) Cross-Couplings with (Fluoro)Alkyl Halides.

PubMed

Ye, Zhishi; Gettys, Kristen E; Shen, Xingyu; Dai, Mingji

2015-12-18

Novel and general copper-catalyzed cyclopropanol ring opening cross-coupling reactions with difluoroalkyl bromides, perfluoroalkyl iodides, monofluoroalkyl bromides, and 2-bromo-2-alkylesters to synthesize various β-(fluoro)alkylated ketones are reported. The reactions feature mild conditions and excellent functional group compatibility and can be scaled up to gram scale. Preliminary mechanistic studies suggest the involvement of radical intermediates. The difluoroalkyl-alkyl cross-coupling products can also be readily converted to more valuable and diverse gem-difluoro-containing compounds by taking advantage of the carbonyl group resulting from cyclopropanol ring opening.

Gold(I)-catalyzed diazo coupling: strategy towards alkene formation and tandem benzannulation.

PubMed

Zhang, Daming; Xu, Guangyang; Ding, Dong; Zhu, Chenghao; Li, Jian; Sun, Jiangtao

2014-10-06

A gold(I)-catalyzed cross-coupling of diazo compounds to afford tetrasubstituted alkenes has been developed by taking advantage of a trivial electronic difference between two diazo substrates. A N-heterocyclic-carbene-derived gold complex is the most effective catalyst for this transformation. Based on this new strategy, a gold(I)-initiated benzannulation has been achieved through a tandem reaction involving a diazo cross-coupling, 6π electrocyclization, and oxidative aromatization. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Ni-Catalyzed Dehydrogenative Cross-Coupling: Direct Transformation of Aldehydes to Esters and Amides

PubMed Central

Whittaker, Aaron M.; Dong, Vy M.

2015-01-01

By exploring a new mode of Ni-catalyzed cross-coupling, we have developed a protocol to transform both aromatic and aliphatic aldehydes into either esters or amides directly. The success of this oxidative coupling depends on the appropriate choice of catalyst and organic oxidant, including the use of either α,α,α-trifluoroacetophenone or excess aldehyde. We present mechanistic data that supports a catalytic cycle involving oxidative addition into the aldehyde C–H bond. PMID:25424967

Design and Synthesis of a Library of Tetracyclic Hydroazulenoisoindoles

PubMed Central

Brummond, Kay M.; Mao, Shuli; Shinde, Sunita N.; Johnston, Paul J.; Day, Billy W.

2009-01-01

Forty-four tetracyclic hydroazulenoisoindoles were synthesized via a tandem cyclopropanation/Cope rearrangement followed by a Diels-Alder sequence from easily available five-membered cyclic cross-conjugated trienones. These trienones were obtained from two different routes depending upon whether R1 and R2 are alkyl or amino acid derived functional groups, via a rhodium(I)-catalyzed cycloisomerization reaction. In order to increase diversity, four maleimides and two 1,2,4-triazoline-3,5-diones were used as dienophiles in the Diels-Alder step. Several Diels-Alder adducts were further reacted under palladium-catalyzed hydrogenation conditions, leading to a diastereoselective reduction of the trisubstituted double bond. This library has demonstrated rapid access to a variety of structurally complex natural product-like compounds via stereochemical diversity and building block diversity approaches. PMID:19366169

Parameterization of phosphine ligands demonstrates enhancement of nickel catalysis via remote steric effects.

PubMed

Wu, Kevin; Doyle, Abigail G

2017-08-01

The field of Ni-catalysed cross-coupling has seen rapid recent growth because of the low cost of Ni, its earth abundance, and its ability to promote unique cross-coupling reactions. Whereas advances in the related field of Pd-catalysed cross-coupling have been driven by ligand design, the development of ligands specifically for Ni has received minimal attention. Here, we disclose a class of phosphines that enable the Ni-catalysed Csp 3 Suzuki coupling of acetals with boronic acids to generate benzylic ethers, a reaction that failed with known ligands for Ni and designer phosphines for Pd. Using parameters to quantify phosphine steric and electronic properties together with regression statistical analysis, we identify a model for ligand success. The study suggests that effective phosphines feature remote steric hindrance, a concept that could guide future ligand design tailored to Ni. Our analysis also reveals that two classic descriptors for ligand steric environment-cone angle and % buried volume-are not equivalent, despite their treatment in the literature.

Parameterization of phosphine ligands demonstrates enhancement of nickel catalysis via remote steric effects

NASA Astrophysics Data System (ADS)

Wu, Kevin; Doyle, Abigail G.

2017-08-01

The field of Ni-catalysed cross-coupling has seen rapid recent growth because of the low cost of Ni, its earth abundance, and its ability to promote unique cross-coupling reactions. Whereas advances in the related field of Pd-catalysed cross-coupling have been driven by ligand design, the development of ligands specifically for Ni has received minimal attention. Here, we disclose a class of phosphines that enable the Ni-catalysed Csp3 Suzuki coupling of acetals with boronic acids to generate benzylic ethers, a reaction that failed with known ligands for Ni and designer phosphines for Pd. Using parameters to quantify phosphine steric and electronic properties together with regression statistical analysis, we identify a model for ligand success. The study suggests that effective phosphines feature remote steric hindrance, a concept that could guide future ligand design tailored to Ni. Our analysis also reveals that two classic descriptors for ligand steric environment—cone angle and % buried volume—are not equivalent, despite their treatment in the literature.

A One-Pot Synthesis of Dibenzofurans from 6-Diazo-2-cyclohexenones.

PubMed

Zhao, Hua; Yang, Ke; Zheng, Hongyan; Ding, Ruichao; Yin, Fangjie; Wang, Ning; Li, Yun; Cheng, Bin; Wang, Huifei; Zhai, Hongbin

2015-12-04

A novel and efficient protocol for the rapid construction of dibenzofuran motifs from 6-diazo-2-cyclohexenone and ortho-haloiodobenzene has been developed. The process involves one-pot Pd-catalyzed cross-coupling/aromatization and Cu-catalyzed Ullmann coupling.

A novel and general synthetic pathway to strychnos indole alkaloids: total syntheses of (-)-tubifoline, (-)-dehydrotubifoline, and (-)-strychnine using palladium-catalyzed asymmetric allylic substitution.

PubMed

Mori, Miwako; Nakanishi, Masato; Kajishima, Daisuke; Sato, Yoshihiro

2003-08-13

A method of palladium-catalyzed asymmetric allylic substitution for synthesizing 2-substituted cyclohexenylamine derivatives was established. Treatment of a 2-silyloxymethylcyclohexenol derivative with ortho-bromo-N-tosylaniline in the presence of Pd(2)dba(3).CHCl(3) and (S)-BINAPO in THF afforded a cyclohexenylamine derivative with 84% ee in 80% yield. The Heck reaction was carried out to produce an indolenine derivative in good yield. Using this method, we synthesized indolenine derivative 7, which was recrystallized from EtOH to give an optically pure compound. From this compound, tetracyclic ketone 13, which should be a useful intermediate for the synthesis of indole alkaloids, could be synthesized. The total syntheses of (-)-dehydrotubifoline, (-)-tubifoline, and (-)-strychnine were achieved from 13. All ring constructions for the syntheses of these natural products were achieved using a palladium catalyst.

One-pot palladium-catalyzed synthesis of sulfonyl fluorides from aryl bromides† †Electronic supplementary information (ESI) available: Experimental details and supporting characterisation data. See DOI: 10.1039/c6sc03924c Click here for additional data file.

PubMed Central

Davies, Alyn T.; Curto, John M.

2017-01-01

A mild, efficient synthesis of sulfonyl fluorides from aryl and heteroaryl bromides utilizing palladium catalysis is described. The process involves the initial palladium-catalyzed sulfonylation of aryl bromides using DABSO as an SO2 source, followed by in situ treatment of the resultant sulfinate with the electrophilic fluorine source NFSI. This sequence represents the first general method for the sulfonylation of aryl bromides, and offers a practical, one-pot alternative to previously described syntheses of sulfonyl fluorides, allowing rapid access to these biologically important molecules. Excellent functional group tolerance is demonstrated, with the transformation successfully achieved on a number of active pharmaceutical ingredients, and their precursors. The preparation of peptide-derived sulfonyl fluorides is also demonstrated. PMID:28451264

A general method for copper-catalyzed arene cross-dimerization.

PubMed

Do, Hien-Quang; Daugulis, Olafs

2011-08-31

A general method for a highly regioselective copper-catalyzed cross-coupling of two aromatic compounds using iodine as an oxidant has been developed. The reactions involve an initial iodination of one arene followed by arylation of the most acidic C-H bond of the other coupling component. Cross-coupling of electron-rich arenes, electron-poor arenes, and five- and six-membered heterocycles is possible in many combinations. Typically, a 1/1.5 to 1/3 ratio of coupling components is used, in contrast to existing methodology that often employs a large excess of one of the arenes. Common functionalities such as ester, ketone, aldehyde, ether, nitrile, nitro, and amine are well-tolerated.

A General Method for Copper-Catalyzed Arene Cross-Dimerization

PubMed Central

Do, Hien-Quang; Daugulis, Olafs

2011-01-01

A general method for a highly regioselective, copper-catalyzed cross-coupling of two aromatic compounds by using iodine oxidant has been developed. The reactions involve an initial iodination of one arene followed by arylation of the most acidic C-H bond of the other coupling component. Cross-coupling of electron-rich arenes, electron-poor arenes, five- and six-membered heterocycles is possible in many combinations. Typically, 1/1.5 to 1/3 ratio of coupling components is used in contrast to existing methodology that often employs a large excess of one of the arenes. Common functionalities such as ester, ketone, aldehyde, ether, nitrile, nitro, and amine are well-tolerated. PMID:21823581

Divergent strategy for the synthesis of alpha-aryl-substituted fosmidomycin analogues.

PubMed

Devreux, Vincent; Wiesner, Jochen; Jomaa, Hassan; Rozenski, Jef; Van der Eycken, Johan; Van Calenbergh, Serge

2007-05-11

Fosmidomycin is the first representative of a new class of antimalarial drugs acting through inhibition of 1-deoxy-D-xylulose 5-phosphate (DOXP) reductoisomerase (DXR), an essential enzyme in the non-mevalonate pathway for the synthesis of isoprenoids. This work describes a divergent strategy for the synthesis of a series of alpha-aryl-substituted fosmidomycin analogues, featuring a palladium-catalyzed Stille coupling as the key step. An alpha-(4-cyanophenyl)fosmidomycin analogue emerged as the most potent analogue in the present series. Its antimalarial activity clearly surpasses that of the reference compound fosmidomycin.

Palladium-Catalyzed Dynamic Kinetic Asymmetric Transformations of Vinyl Aziridines with Nitrogen Heterocycles: Rapid Access to Biologically Active Pyrroles and Indoles

PubMed Central

Trost, Barry M.; Osipov, Maksim; Dong, Guangbin

2010-01-01

We report that nitrogen heterocycles can serve as competent nucleophiles in the palladium-catalyzed dynamic kinetic asymmetric alkylation of vinyl aziridines. The resulting alkylated products were obtained with high regio-, chemo-, and enantioselectivity. Both substituted 1H-pyrroles and 1H-indoles were successfully employed to give exclusively the branched N-alkylated products. The synthetic utility of this process was demonstrated by applying this method to the preparation of several medicinal chemistry lead compounds and bromopyrrole alkaloids including longamide B, longamide B methyl ester, hanishin, agesamides A and B, and cyclooroidin. PMID:20949972

Palladium-catalyzed cyclization reactions of 2-vinylthiiranes with heterocumulenes. Regioselective and enantioselective formation of thiazolidine, oxathiolane, and dithiolane derivatives.

PubMed

Larksarp, C; Sellier, O; Alper, H

2001-05-18

The first palladium-catalyzed ring-expansion reaction of 2-vinylthiiranes with heterocumulenes to form sulfur-containing five-membered-ring heterocycles is described. This regioselective reaction requires 5 mol % of Pd(2)(dba)(3).CHCl(3) and 10 mol % of bidendate phosphine ligand (dppp, BINAP), at 50-80 degrees C, in THF. The reaction of 2-vinylthiiranes with carbodiimides, isocyanates, and ketenimines affords 1,3-thiazolidine derivatives, whereas the reaction with diphenylketene or isothiocyanates results in the formation of 1,3-oxathiolane or 1,3-dithiolane compounds in good to excellent isolated yields and in up to 78% ee.

Synthesis of Dichlorophosphinenickel(II) Compounds and Their Catalytic Activity in Suzuki Cross-Coupling Reactions: A Simple Air-Free Experiment for Inorganic Chemistry Laboratory

ERIC Educational Resources Information Center

Thananatthanachon, Todsapon; Lecklider, Michelle R.

2017-01-01

In this experiment, students perform an air-free synthesis of three dichlorophosphinenickel(II) compounds, NiCl[subscript 2](PPh[subscript 3])[subscript 2], NiCl[subscript 2](PCy[subscript 3])[subscript 2], and NiCl[subscript 2](DPPE), using NiCl[subscript 2]·6H[subscript 2]O and the appropriate phosphine as the precursors. These colorful nickel…

I. Development of Metal-Mediated SPOT-Synthesis Methods for the Efficient Construction of Small-Molecule Macroarrays. II. Design and Synthesis of Novel Bacterial Biofilm Inhibitors

NASA Astrophysics Data System (ADS)

Frei, Reto

I. The use of small molecule probes to explore biological phenomena has become a valuable tool in chemical biology. As a result, methods that permit the rapid synthesis and biological evaluation of such compounds are highly sought-after. The small molecule macroarray represents one such approach for the synthesis and identification of novel bioactive agents. Macroarrays are readily constructed via the SPOT-synthesis technique on planar cellulose membranes, yielding spatially addressed libraries of ˜10-1000 unique compounds. We sought to expand the arsenal of chemical reactions compatible with this solid-phase platform, and developed highly efficient SPOT-synthesis protocols for the Mizoroki-Heck, Suzuki-Miyaura, and copper-catalyzed azide-alkyne cycloaddition reaction. We demonstrated that these metal-mediated reactions can be implemented, either individually or sequentially, for the efficient construction of small molecules in high purity on rapid time scales. Utilizing these powerful C-C and C-N bond forming coupling reactions, we constructed a series of macroarrays based on novel stilbene, phenyl-naphthalene, and triazole scaliblds. Subsequent biological testing of the stilbene and phenyl-naphthalene libraries revealed several potent antagonists and agonists, respectively, of the quorum sensing (QS) receptor LuxR in Vibrio fischeri. II. Bacteria living within biofilms are notorious for their resistance to known antibiotic agents, and constitute a major human health threat. Methods to attenuate biofilm growth would have a significant impact on the management of bacterial infections. Despite intense research efforts, small molecules capable of either inhibiting or dispersing biolilms remain scarce. We utilized natural products with purported anti-biofilm or QS inhibitory activity as sources of structural insight to guide the synthesis of novel biofilm modulators with improved activities. These studies revealed 2-aminobenzimidazole derivatives as highly potent biofilm inhibitors and dispersers in the opportunistic pathogen Pseudomonas aeruginosa. Studies of second-generation 2-aminobenzimidazoles revealed important structure-activity relationships that guided the design of yet more potent analogs. These compounds are amongst the most potent inhibitors of biofilm formation in wild-type P. aeruginosa to be reported. Mechanistic studies of the most active compounds suggest that QS inhibition is one pathway by which 2-aminobenzimidazoles modulate biofilm growth.

HYDRODEHALOGENATION OF 1- TO 3-CARBON HALOGENATED ORGANIC COMPOUNDS IN WATER USING A PALLADIUM CATALYST AND HYDROGEN GAS. (R825421)

EPA Science Inventory

Supported palladium (Pd) metal catalysts along with H₂ gas show
significant potential as a technology which can provide rapid, on-site
destruction of halogenated groundwater contaminants. Pd catalyzes the rapid
hydrodehalogenation of nine 1- to 3-carbon ...

Single-Electron Transmetalation via Photoredox/Nickel Dual Catalysis: Unlocking a New Paradigm for sp(3)-sp(2) Cross-Coupling.

PubMed

Tellis, John C; Kelly, Christopher B; Primer, David N; Jouffroy, Matthieu; Patel, Niki R; Molander, Gary A

2016-07-19

The important role of transition metal-catalyzed cross-coupling in expanding the frontiers of accessible chemical territory is unquestionable. Despite empowering chemists with Herculean capabilities in complex molecule construction, contemporary protocols are not without their Achilles' heel: Csp(3)-Csp(2)/sp(3) coupling. The underlying challenge in sp(3) cross-couplings is 2-fold: (i) methods employing conventional, bench-stable precursors are universally reliant on extreme reaction conditions because of the high activation barrier of transmetalation; (ii) circumvention of this barrier invariably relies on use of more reactive precursors, thereby sacrificing functional group tolerance, operational simplicity, and broad applicability. Despite the ubiquity of this problem, the nature of the transmetalation step has remained unchanged from the seminal reports of Negishi, Suzuki, Kumada, and Stille, thus suggesting that the challenges in Csp(3)-Csp(2)/sp(3) coupling result from inherent mechanistic constraints in the traditional cross-coupling paradigm. Rather than submitting to the limitations of this conventional approach, we envisioned that a process rooted in single-electron reactivity could furnish the same key metalated intermediate posited in two-electron transmetalation, while demonstrating entirely complementary reactivity patterns. Inspired by literature reports on the susceptibility of organoboron reagents toward photochemical, single-electron oxidative fragmentation, realization of a conceptually novel open shell transmetalation framework was achieved in the facile coupling of benzylic trifluoroborates with aryl halides via cooperative visible-light activated photoredox and Ni cross-coupling catalysis. Following this seminal study, we disclosed a suite of protocols for the cross-coupling of secondary alkyl, α-alkoxy, α-amino, and α-trifluoromethylbenzyltrifluoroborates. Furthermore, the selective cross-coupling of Csp(3) organoboron moieties in the presence of Csp(2) organoboron motifs was also demonstrated, highlighting the nuances of this approach to transmetalation. Computational modeling of the reaction mechanism uncovered useful details about the intermediates and transition-state structures involved in the nickel catalytic cycle. Most notably, a unique dynamic kinetic resolution process, characterized by radical homolysis/recombination equilibrium of a Ni(III) intermediate, was discovered. This process was ultimately found to be responsible for stereoselectivity in an enantioselective variant of these cross-couplings. Prompted by the intrinsic limitations of organotrifluoroborates, we sought other radical feedstocks and quickly identified alkylbis(catecholato)silicates as viable radical precursors for Ni/photoredox dual catalysis. These hypervalent silicate species have several notable benefits, including more favorable redox potentials that allow extension to primary alkyl systems incorporating unprotected amines as well as compatibility with less expensive Ru-based photocatalysts. Additionally, these reagents exhibit an amenability to alkenyl halide cross-coupling while simultaneously expanding the aryl halide scope. In the process of exploring these reagents, we serendipitously discovered a method to effect thioetherification of aryl halides via a H atom transfer mechanism. This latter discovery emphasizes that this robust cross-coupling paradigm is "blind" to the origins of the radical, opening opportunities for a wealth of new discoveries. Taken together, our studies in the area of photoredox/nickel dual catalysis have validated single-electron transmetalation as a powerful platform for enabling conventionally challenging Csp(3)-Csp(2) cross-couplings. More broadly, these findings represent the power of rational design in catalysis and the strategic use of mechanistic knowledge and manipulation for the development of new synthetic methods.

Highly Reactive, General and Long-Lived Catalysts for Palladium-Catalyzed Amination of Heteroaryl and Aryl Chlorides, Bromides and Iodides: Scope and Structure-Activity Relationships

PubMed Central

Shen, Qilong; Ogata, Tokutaro; Hartwig, John F.

2010-01-01

We describe a systematic study of the scope and relationship between ligand structure and activity for a highly efficient and selective class of catalysts for the amination of heteroaryl and aryl chlorides, bromides and iodides containing sterically hindered chelating alkylphosphines. In the presence of this catalyst, aryl and heteroaryl chlorides, bromides and iodides react with many primary amines in high yields with part-per-million quantities of palladium precursor and ligand. Many reactions of primary amines with both heteroaryl and aryl chlorides, bromides and iodides occur to completion with 0.0005-0.05 mol % catalysts. A comparison of the reactivity of this catalyst for coupling of primary amines at these loadings is made with catalysts generated from hindered monophosphines and carbenes, and these data illustrate the benefits of chelation. Thus, these complexes constitute a fourth-generation catalyst for the amination of aryl halides, whose activity complements catalysts based on monophosphines and carbenes. PMID:18444639

Stabilization of Two Radicals with One Metal: A Stepwise Coupling Model for Copper-Catalyzed Radical–Radical Cross-Coupling

PubMed Central

Qi, Xiaotian; Zhu, Lei; Bai, Ruopeng; Lan, Yu

2017-01-01

Transition metal-catalyzed radical–radical cross-coupling reactions provide innovative methods for C–C and C–heteroatom bond construction. A theoretical study was performed to reveal the mechanism and selectivity of the copper-catalyzed C–N radical–radical cross-coupling reaction. The concerted coupling pathway, in which a C–N bond is formed through the direct nucleophilic addition of a carbon radical to the nitrogen atom of the Cu(II)–N species, is demonstrated to be kinetically unfavorable. The stepwise coupling pathway, which involves the combination of a carbon radical with a Cu(II)–N species before C–N bond formation, is shown to be probable. Both the Mulliken atomic spin density distribution and frontier molecular orbital analysis on the Cu(II)–N intermediate show that the Cu site is more reactive than that of N; thus, the carbon radical preferentially react with the metal center. The chemoselectivity of the cross-coupling is also explained by the differences in electron compatibility of the carbon radical, the nitrogen radical and the Cu(II)–N intermediate. The higher activation free energy for N–N radical–radical homo-coupling is attributed to the mismatch of Cu(II)–N species with the nitrogen radical because the electrophilicity for both is strong. PMID:28272407

Remote C-H Functionalization by a Palladium-Catalyzed Transannular Approach.

PubMed

De Sarkar, Suman

2016-08-26

Now within reach: In the remote C-H arylation of alicyclic amines the key step is the transannular coordination of the palladium catalyst (see picture, DG=directing group). This strategy is convenient for the late-stage functionalization of complex bioactive molecules in order to probe structure-activity relationships. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Carbon-coated magnetic palladium: applications in partial oxidation of alcohols and coupling reactions.

EPA Science Inventory

Magnetic carbon supported Pd catalyst has been synthesized via in situ generation of nanoferrites and incorporation of carbon from renewable cellulose via calcination; catalyst can be used for oxidation of alcohols, amination reaction and arylation of aryl halides (cross coupli...

The Stille Reaction (Vittorio Farina, Venkat Krishnamurthy, and William J. Scott)

NASA Astrophysics Data System (ADS)

Cochran, John C.

1999-10-01

In 1997, Volume 50 of Organic Reactions was published in a handsome and appropriate gold hard-cover edition. This was only the third volume in this prestigious series that consisted of a single chapter. The treatise, The Stille Reaction, describes a palladium-catalyzed cross-coupling between a carbon ligand on tin and a carbon with electrophilic character. This reaction has been around only since 1977, and the literature is covered here through 1994 with a few references in 1995. It is truly astounding that, in the space of about 17 years, a new reaction could generate enough literature for not only a chapter in Organic Reactions, but a complete volume of 652 pages, 864 literature citations, and more than 4300 specific reaction examples. The editorial board of Organic Reactions has graciously decided to make this extensive review available to a broader audience by authorizing a paperback edition of The Stille Reaction. While the mechanistic details of the Stille reaction are generally understood, there are many fine points that must be tuned to each case. For instance, about 15 different solvents have been used, ranging in polarity from benzene to water; at least ten different ligands for the palladium atom are available and they range from hard to soft; CuI, Ag2CO3, and LiCl are sometimes useful cocatalysts but sometimes have no effect, and in some cases LiCl is inhibitory; vinyl triflates couple with alkenyl-, alkynyl- and allylstannanes but not with arylstannanes; reaction temperatures vary from room temperature to refluxing DMF. An important consideration is that most stannanes are reasonably air and moisture stable and do not react with most common functional groups. Thus, it is not necessary to build protection-deprotection sequences into the synthetic scheme. The extensive reaction examples are arranged in 33 tables that show, for each reaction, the structures of the electrophile, the stannane, and the product and specify the catalyst, cocatalyst, solvent temperature, and yield. The tables are sequenced by the structure of the electrophiles, which are listed in order of increasing carbon count for the group that is transferred. For the same electrophile, different stannanes are listed by the increasing carbon count of the group transferred from tin. For example, the three tables with the most examples are titled "Direct Cross-Coupling of Alkenyl Electrophiles," "Direct Cross-Coupling of Aryl Electrophiles", and "Direct Cross-Coupling of Miscellaneous Heterocyclic Electrophiles". They include 661, 1043, and 339 examples, respectively. The narrative section of the book begins with an overview of the mechanism, regiochemistry, and stereochemistry of the Stille reaction. This is followed by discussions of the scope and limitations of both the electrophilic species and the stannane. The Stille reaction can also involve the incorporation of a carbonyl in the coupling sequence. The carbonyl results from inclusion of carbon monoxide in the reaction medium. This variation of the reaction is also discussed. The narrative continues with discussion of Hech-Stille tandem sequences, side reactions, and comparisons with other cross-coupling reactions. It concludes with a very useful section on experimental considerations and nine examples of procedures from the literature. The book also includes a useful index (covering the narrative section), which has been added to the original Organic Reactions edition. Finally, it should be noted that a careful inspection of the thousands of structures in the table did not turn up one typographical error. In a 1993 research paper (J. Org. Chem. 1993, 58, 5434) the lead author, Vittorio Farina, writes that "A survey of applications of transition metal-mediated cross-coupling reactions for the year 1992 shows that the Stille coupling accounts for over 50% of all cross-couplings reported." It seems that, given the magnitude of this review, the significance of this reaction has continued to grow. Every synthetic organic chemist should have easy access to the massive amount of information contained in this book.

Regioselective palladium-catalyzed ring-opening reactions of C1-substituted oxabicyclo[2,2,1]hepta-2,5-diene-2,3-dicarboxylates

PubMed Central

Edmunds, Michael; Raheem, Mohammed Abdul; Boutin, Rebecca; Tait, Katrina

2016-01-01

Summary Palladium-catalyzed ring-opening reactions of C1 substituted 7-oxanorbornadiene derivatives with aryl iodides were investigated. The optimal conditions for this reaction were found to be PdCl2(PPh3)2, ZnCl2, Et3N and Zn in THF. Both steric and electronic factors played a role in the outcome of the reaction as increasing the steric bulk on the bridgehead carbon decreased the yield. These reactions were found to be highly regioselective, giving only one of the two possible regioisomers in all cases. A diverse collection of novel, highly substituted biphenyl derivatives were obtained. PMID:26977182

Palladium-catalyzed cyclocoupling of 2-halobiaryls with isocyanides via the cleavage of carbon-hydrogen bonds.

PubMed

Tobisu, Mamoru; Imoto, Shinya; Ito, Sana; Chatani, Naoto

2010-07-16

To demonstrate the utility of isocyanides in catalytic C-H bond functionalization reactions, a palladium-catalyzed cyclocoupling reaction of 2-halobiaryls with isocyanides was developed. The reaction afforded an array of fluorenone imine derivatives via the cleavage of a C-H bond at the 2'-position of 2-halobiaryls. The use of 2,6-disubstituted phenyl isocyanide was crucial for this catalytic cyclocoupling reaction to proceed. The reaction was applicable to heterocyclic and vinylic substrates, allowing the construction of a wide range of ring system. The large kinetic isotope effect observed (k(H)/k(D) = 5.3) indicates that C-H bond activation was the turnover-limiting step in this catalysis.

Scope and mechanism in palladium-catalyzed isomerizations of highly substituted allylic, homoallylic, and alkenyl alcohols.

PubMed

Larionov, Evgeny; Lin, Luqing; Guénée, Laure; Mazet, Clément

2014-12-03

Herein we report the palladium-catalyzed isomerization of highly substituted allylic alcohols and alkenyl alcohols by means of a single catalytic system. The operationally simple reaction protocol is applicable to a broad range of substrates and displays a wide functional group tolerance, and the products are usually isolated in high chemical yield. Experimental and computational mechanistic investigations provide complementary and converging evidence for a chain-walking process consisting of repeated migratory insertion/β-H elimination sequences. Interestingly, the catalyst does not dissociate from the substrate in the isomerization of allylic alcohols, whereas it disengages during the isomerization of alkenyl alcohols when additional substituents are present on the alkyl chain.

Merging C-H activation and alkene difunctionalization at room temperature: a palladium-catalyzed divergent synthesis of indoles and indolines.

PubMed

Manna, Manash Kumar; Hossian, Asik; Jana, Ranjan

2015-02-06

A palladium-catalyzed 1,2-carboamination through C-H activation at room temperature is reported for the synthesis of 2-arylindoles, and indolines from readily available, inexpensive aryl ureas and vinyl arenes. The reaction initiates with a urea-directed electrophilic ortho palladation, alkene insertion, and β-hydride elimination sequences to provide the Fujiwara-Moritani arylation product. Subsequently, aza-Wacker cyclization, and β-hydride elimination provide the 2-arylindoles in high yields. Intercepting the common σ-alkyl-Pd intermediate, corresponding indolines are also achieved. The indoline formation is attributed to the generation of stabilized, cationic π-benzyl-Pd species to suppress β-hydride elimination.

Selective Formation of Secondary Amides via the Copper-Catalyzed Cross-Coupling of Alkylboronic Acids with Primary Amides

PubMed Central

Rossi, Steven A.; Shimkin, Kirk W.; Xu, Qun; Mori-Quiroz, Luis M.; Watson, Donald A.

2014-01-01

For the first time, a general catalytic procedure for the cross coupling of primary amides and alkylboronic acids is demonstrated. The key to the success of this reaction was the identification of a mild base (NaOSiMe3) and oxidant (di-tert-butyl peroxide) to promote the copper-catalyzed reaction in high yield. This transformation provides a facile, high-yielding method for the mono-alkylation of amides. PMID:23611591

Stereospecific nickel-catalyzed cross-coupling reactions of alkyl Grignard reagents and identification of selective anti-breast-cancer agents.

PubMed

Yonova, Ivelina M; Johnson, A George; Osborne, Charlotte A; Moore, Curtis E; Morrissette, Naomi S; Jarvo, Elizabeth R

2014-02-24

Alkyl Grignard reagents that contain β-hydrogen atoms were used in a stereospecific nickel-catalyzed cross-coupling reaction to form C(sp(3))-C(sp(3)) bonds. Aryl Grignard reagents were also utilized to synthesize 1,1-diarylalkanes. Several compounds synthesized by this method exhibited selective inhibition of proliferation of MCF-7 breast cancer cells. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Synthesis and photophysical properties of a series of cyclopenta[b]naphthalene solvatochromic fluorophores.

PubMed

Benedetti, Erica; Kocsis, Laura S; Brummond, Kay M

2012-08-01

The synthesis and photophysical properties of a series of naphthalene-containing solvatochromic fluorophores are described within. These novel fluorophores are prepared using a microwave-assisted dehydrogenative Diels-Alder reaction of styrene, followed by a palladium-catalyzed cross coupling reaction to install an electron donating amine group. The new fluorophores are structurally related to Prodan. Photophysical properties of the new fluorophores were studied and intriguing solvatochromic behavior was observed. For most of these fluorophores, high quantum yields (60-99%) were observed in methylene chloride in addition to large Stokes shifts (95-226 nm) in this same solvent. As the solvent polarity increased, so did the observed Stokes shift with one derivative displaying a Stokes shift of ~300 nm in ethanol. All fluorophore emission maxima, and nearly all absorption maxima were significantly red-shifted when compared to Prodan. Shifting the absorption and emission maxima of a fluorophore into the visible region increases its utility in biological applications. Moreover, the cyclopentane portion of the fluorophore structure provides an attachment point for biomolecules that will minimize disruptions of the photophysical properties.

Anionic Palladium(0) and Palladium(II) Ate Complexes.

PubMed

Kolter, Marlene; Böck, Katharina; Karaghiosoff, Konstantin; Koszinowski, Konrad

2017-10-16

Palladium ate complexes are frequently invoked as important intermediates in Heck and cross-coupling reactions, but so far have largely eluded characterization at the molecular level. Here, we use electrospray-ionization mass spectrometry, electrical conductivity measurements, and NMR spectroscopy to show that the electron-poor catalyst [L 3 Pd] (L=tris[3,5-bis(trifluoromethyl)phenyl]phosphine) readily reacts with Br - ions to afford the anionic, zero-valent ate complex [L 3 PdBr] - . In contrast, more-electron-rich Pd catalysts display lower tendencies toward the formation of ate complexes. Combining [L 3 Pd] with LiI and an aryl iodide substrate (ArI) results in the observation of the Pd II ate complex [L 2 Pd(Ar)I 2 ] - . © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Enantioselective synthesis of chiral isotopomers of 1-alkanols by a ZACA-Cu-catalyzed cross-coupling protocol.

PubMed

Xu, Shiqing; Oda, Akimichi; Negishi, Ei-ichi

2014-12-01

Chiral compounds arising from the replacement of hydrogen atoms by deuterium are very important in organic chemistry and biochemistry. Some of these chiral compounds have a non-measurable specific rotation, owing to very small differences between the isotopomeric groups, and exhibit cryptochirality. This particular class of compounds is difficult to synthesize and characterize. Herein, we present a catalytic and highly enantioselective conversion of terminal alkenes to various β and more remote chiral isotopomers of 1-alkanols, with ≥99 % enantiomeric excess (ee), by the Zr-catalyzed asymmetric carboalumination of alkenes (ZACA) and Cu-catalyzed cross-coupling reactions. ZACA-in situ iodinolysis of allyl alcohol and ZACA-in situ oxidation of TBS-protected ω-alkene-1-ols protocols were applied to the synthesis of both (R)- and (S)-difunctional intermediates with 80-90 % ee. These intermediates were readily purified to provide enantiomerically pure (≥99 % ee) compounds by lipase-catalyzed acetylation. These functionally rich intermediates serve as very useful synthons for the construction of various chiral isotopomers of 1-alkanols in excellent enantiomeric purity (≥99 % ee) by introducing deuterium-labeled groups by Cu-catalyzed cross-coupling reactions without epimerization. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

One-pot synthesis of keto thioethers by palladium/gold-catalyzed click and pinacol reactions.

PubMed

Cadu, Alban; Watile, Rahul A; Biswas, Srijit; Orthaber, Andreas; Sjöberg, Per J R; Samec, Joseph S M

2014-11-07

An atom-efficient synthesis of keto thioethers was devised via tandem gold/palladium catalysis. The reaction proceeds through a regioselective thiol attack at the β-position of the alcohol, followed by an alkyl, aryl, or benzyl 1,2-shift. Both acyclic and cyclic systems were studied, in the latter case leading to the ring expansion of cyclic substrates.

Synergistic N-Heterocyclic Carbene/Palladium-Catalyzed Reactions of Aldehyde Acyl Anions with either Diarylmethyl or Allylic Carbonates.

PubMed

Yasuda, Shigeo; Ishii, Takuya; Takemoto, Shunsuke; Haruki, Hiroki; Ohmiya, Hirohisa

2018-03-05

Benzylation and allylation of aldehyde acyl anions were enabled by the merger of a thiazolium N-heterocyclic carbene (NHC) catalyst and a palladium/bisphosphine catalyst in a synergistic manner. Owing to the mildness of the reaction conditions, various functional groups were tolerated in the substrates. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

A general palladium-catalyzed carbonylative synthesis of chromenones from salicylic aldehydes and benzyl chlorides.

PubMed

Wu, Xiao-Feng; Wu, Lipeng; Jackstell, Ralf; Neumann, Helfried; Beller, Matthias

2013-09-09

Cute CO! An interesting and straightforward procedure for the carbonylative synthesis of chromenones from readily available salicylic aldehydes and benzyl chlorides has been developed (see scheme; DPPP = 1,3-bis(diphenylphosphino)propane). In the presence of a palladium catalyst, various coumarins were produced in good to excellent yields. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Pd-catalyzed allylic alkylation of dienyl carbonates with nitromethane with high C-5 regioselectivity.

PubMed

Yang, Xiao-Fei; Li, Xiao-Hui; Ding, Chang-Hua; Xu, Chao-Fan; Dai, Li-Xin; Hou, Xue-Long

2014-01-14

A highly regioselective palladium-catalyzed allylic alkylation of dienyl esters with nitromethane has been developed, providing selective access to the C-5 attacked products. The structures of the ligands as well as the steric effect of the substrates are important factors in determining the regiochemical outcome of the reaction.

Visible-Light-Mediated Nickel(II)-Catalyzed C-N Cross-Coupling in Water: Green and Regioselective Access for the Synthesis of Pyrazole-Containing Compounds.

PubMed

You, Guirong; Wang, Kai; Wang, Xiaodan; Wang, Guodong; Sun, Jian; Duan, Guiyun; Xia, Chengcai

2018-06-26

A regioselective green approach for the nickel(II)-catalyzed C-N cross-coupling between arylamines and pyrazoles through a photoredox process is reported. Moderate to good yield was observed for this reaction, performed in water under air at room temperature. This strategy provides a powerful tool for the green synthesis of pyrazole-containing bioactive molecules. In addition, a single-electron-transfer mechanism is proposed in this report.

Synthesis of isoflavones by room-temperature nickel-catalyzed cross-couplings of 3-iodo(bromo)chromones with arylzincs.

PubMed

Zhang, Zunting; Qiao, Jinfeng; Wang, Ding; Han, Ling; Ding, Ru

2014-05-01

A new concise, facile method for synthesis of isoflavones was accomplished in moderate to good yields for 3-iodochromones or 3-bromochromones and arylzinc bromides via Negishi cross-coupling reaction catalyzed by NiCl(2)/PPh(3) or NiCl(2)(PPh(3))(2) at room temperature. The Isoflavone core was synthesized in four steps in good yield, starting from commercially available 2-hydroxyacetophenone and aromatic bromide. Three steps of the procedure were carried out at room temperature.

Gold(I)-catalyzed diazo cross-coupling: a selective and ligand-controlled denitrogenation/cyclization cascade.

PubMed

Xu, Guangyang; Zhu, Chenghao; Gu, Weijin; Li, Jian; Sun, Jiangtao

2015-01-12

An unprecedented gold-catalyzed ligand-controlled cross-coupling of diazo compounds by sequential selective denitrogenation and cyclization affords N-substituted pyrazoles in a position-switchable mode. This novel transformation features selective decomposition of one diazo moiety and simultaneous preservation of the other one from two substrates. Notably, the choice of the ancillary ligand to the gold complex plays a pivotal role on the chemo- and regioselectivity of the reactions. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Synthesis of Pd-N-heterocyclic carbene Pd-catalyst and its application in MW-assisted Heck and Suzuki reaction

EPA Science Inventory

The first Pd-N-heterocyclic carbene (NHC) complex in the form of organic silica is prepared using sol-gel method and its application in Heck and Suzuki reactions are demonstrated. These C-C coupling reactions proceeded efficiently under the influence of microwave irradiation, wit...

Hetero-bivalent Imaging Agents for Simultaneous Targeting Prostate-Specific Membrane Antigen (PSMA) and Hepsin

DTIC Science & Technology

2013-09-01

Suzuki cross-coupling reaction. The effects of solvent and base on the synthesis of 3 were studied using Pd(PPh3)4 as catalyst . DMF, ethanol, and DMSO...PSMA/hepsin for in vitro cell uptake and in vivo imaging studies . Compound 13 showed a low but detectable increased cell uptake into the developed...have been comprehensive clinical studies whether PSA testing is an efficient biomarker in diagnosing PCa and reducing PCa deaths. Two European studies

Palladium-Catalyzed Reductive Insertion of Alcohols into Aryl Ether Bonds

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Meng; Gutiérrez, Oliver Y.; Camaioni, Donald M.

Pd/C catalyzes C-O bond cleavage of aryl ethers (diphenyl ether and cyclohexyl phenyl ether) by methanol in H2. The aromatic C-O bond is cleaved by reductive methanolysis, which is initiated by Pd-catalyzed partial hydrogenation of one phenyl ring to form an enol ether. The enol ether reacts rapidly with methanol to form a ketal, which generates methoxycyclohexene by eliminating phenol or an alkanol. Subsequent hydrogenation leads to methoxycyclohexane.

Decarbonylative Cross-Couplings: Nickel Catalyzed Functional Group Interconversion Strategies for the Construction of Complex Organic Molecules.

PubMed

Guo, Lin; Rueping, Magnus

2018-05-15

The utilization of carboxylic acid esters as electrophiles in metal-catalyzed cross-coupling reactions is increasingly popular, as environmentally friendly and readily available ester derivatives can be powerful alternatives to the commonly used organohalides. However, key challenges associated with the use of these chemicals remain to be addressed, including the stability of ester substrates and the high energy barrier associated with their oxidative addition to low-valent metal species. Due to recent developments in nickel catalysis that make it easier to perform oxidative additions, chemists have become interested in applying less reactive electrophiles as coupling counterparts in nickel-catalyzed transformations. Hence, our group and others have independently investigated various ester group substitutions and functionalizations enabled by nickel catalysis. Such methods are of great interest as they enable the exchange of ester groups, which can be used as directing groups in metal-catalyzed C-H functionalizations prior to their replacement. Here, we summarize our recent efforts toward the development of nickel-catalyzed decarbonylative cross-coupling reactions of carboxylic esters. Achievements accomplished by other groups in this area are also included. To this day, a number of new transformations have been successfully developed, including decarbonylative arylations, alkylations, cyanations, silylations, borylations, aminations, thioetherifications, stannylations, and hydrogenolysis reactions. These transformations proceed via a nickel-catalyzed decarbonylative pathway and have shown a high degree of reactivity and chemoselectivity, as well as several other unique advantages in terms of substrate availability, due to the use of esters as coupling partners. Although the mechanisms of these reactions have not yet been fully understood, chemists have already provided some important insights. For example, Yamamoto explored the stoichiometric nickel-mediated decarbonylation process of esters and proposed a reaction mechanism involving a C(acyl)-O bond cleavage and a CO extrusion. Key nickel intermediates were isolated and characterized by Shi and co-workers, supporting the assumption of a nickel/ N-heterocyclic carbene-promoted C(acyl)-O bond activation and functionalization. Our combined experimental and computational study of a ligand-controlled chemoselective nickel-catalyzed cross-coupling of aromatic esters with alkylboron reagents provided further insight into the reaction mechanism. We demonstrated that nickel complexes with bidentate ligands favor the C(aryl)-C bond cleavage in the oxidative addition step, resulting in decarbonylative alkylations, while nickel complexes with monodentate phosphorus ligands promote the activation of the C(acyl)-O bond, leading to the production of ketone products. Although more detailed mechanistic investigations need to be undertaken, the successful development of decarbonylative cross-coupling reactions can serve as a solid foundation for future studies. We believe that this type of decarbonylative cross-coupling reactions will be of significant value, in particularly in combination with the retrosynthetic analysis and synthesis of natural products and biologically active molecules. Thus, the presented ester substitution methods will pave the way for successful applications in the construction of complex frameworks by late-stage modification and functionalization of carboxylic acid derivatives.

Synthesis of aryl pyrazole via Suzuki coupling reaction, in vitro mushroom tyrosinase enzyme inhibition assay and in silico comparative molecular docking analysis with Kojic acid.

PubMed

Channar, Pervaiz Ali; Saeed, Aamer; Larik, Fayaz Ali; Batool, Bakhtawar; Kalsoom, Saima; Hasan, M M; Erben, Mauricio F; El-Seedi, Hesham R; Ali, Musrat; Ashraf, Zaman

2018-04-30

Aryl pyrazoles are well recognized class of heterocyclic compounds found in several commercially available drugs. Owing to their significance in medicinal chemistry, in this current account we have synthesized a series of suitably substituted aryl pyrazole by employing Suzuki cross-coupling reaction. All compounds were evaluated for inhibition of mushroom tyrosinase enzyme both in vitro and in silico. Compound 3f (IC 50  = 1.568 ± 0.01 µM) showed relatively better potential compared to reference kojic acid (IC 50  = 16.051 ± 1.27 µM). A comparative docking studies showed that compound 3f have maximum binding affinity against mushroom tyrosinase (PDBID: 2Y9X) with binding energy value (-6.90 kcal/mol) as compared to Kojic acid. The 4-methoxy group in compound 3f shows 100% interaction with Cu. Compound 3f displayed hydrogen binding interaction with His61 and His94 at distance of 1.71 and 1.74 Å which might be responsible for higher activity compared to Kojic acid. Copyright © 2018 Elsevier Inc. All rights reserved.

Palladium-catalyzed reactions in the synthesis of 3- and 4-substituted indoles. 4

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hegedus, L.S.; Sestrick, M.R.; Michaelson, E.T.

1989-08-18

4-Bromo-1-tosylindole (1) was converted to tricyclic indole enone 11, a potential intermediate in the synthesis of tetracyclic ergot alkaloids, by a series of palladium-catalyzed processes. Attempts to construct the ergot D ring by the hetero-Diels-Alder reaction of enone 11 and 1-azabutadiene 12 produced not the expected (4 + 2) adduct 13 but the benz(cd)indoline derivative 14 resulting from attack of the aza diene at the indole 2-position. The thermodynamic stability of the naphthol nucleus makes enone 11 generally susceptible to attack at the indole 2-position, as evidenced by the attack of hydride and methyl cuprate nucleophiles at this portion formingmore » indolines 16 and 17, respectively.« less

Copper/amino acid catalyzed cross-couplings of aryl and vinyl halides with nucleophiles.

PubMed

Ma, Dawei; Cai, Qian

2008-11-18

Copper-assisted Ullmann-type coupling reactions are valuable transformations for organic synthesis. Researchers have extensively applied these reactions in both academic and industrial settings. However, two important issues, the high reaction temperatures (normally above 150 degrees C) and the stoichiometric amounts of copper necessary, have greatly limited the reaction scope. To solve these problems, we and other groups have recently explored the use of special ligands to promote these coupling reactions. We first showed that the structure of alpha-amino acids can accelerate Cu-assisted Ullmann reactions, leading to the coupling reactions of aryl halides and alpha-amino acids at 80-90 degrees C. In response to these encouraging results, we also discovered that an l-proline ligand facilitated the following transformations: (1) coupling of aryl halides with primary amines, cyclic secondary amines, and N-containing heterocycles at 40-90 degrees C; (2) coupling of aryl halides with sulfinic acid salts at 80-95 degrees C; (3) azidation of aryl halides and vinyl halides with sodium azide at 40-95 degrees C; (4) coupling of aryl halides with activated methylene compounds at 25-50 degrees C. In addition, we found that N,N-dimethylglycine as a ligand facilitated Cu-catalyzed biaryl ether formation at 90 degrees C. Moreover, Sonogashira reactions worked in the absence of palladium and phosphine ligands, forming enamides from vinyl halides and amides at temperatures ranging from ambient temperature up to 80 degrees C. Furthermore, we discovered that an ortho-amide group can accelerate some Ullmann-type reactions. This functional group in combination with other ligand effects allowed for aryl amination or biaryl ether formation at ambient temperature. The coupling between aryl halides and activated methylene compounds even proceeded at -45 degrees C to enantioselectively form a quaternary carbon center. Taking advantage of these results, we developed several novel approaches for the synthesis of pharmaceutically important heterocycles: 1,2-disubstituted benzimidazoles, polysubstituted indoles, N-substituted 1,3-dihydrobenzimidazol-2-ones, and substituted 3-acyl oxindoles. Our results demonstrate that an l-proline or N,N-dimethylglycine ligand can facilitate most typical Ullmann-type reactions, with reactions occurring under relatively mild conditions and using only 2-20 mol % copper catalysts. These conveniently available and inexpensive catalytic systems not only accelerate the reactions but also tolerate many more functional groups. Thus, they should find considerable application in organic synthesis.

Monodisperse gold-palladium alloy nanoparticles and their composition-controlled catalysis in formic acid dehydrogenation under mild conditions.

PubMed

Metin, Önder; Sun, Xiaolian; Sun, Shouheng

2013-02-07

Monodisperse 4 nm AuPd alloy nanoparticles with controlled composition were synthesized by co-reduction of hydrogen tetrachloroaurate(III) hydrate and palladium(II) acetylacetonate with a borane-morpholine complex in oleylamine. These NPs showed high activity (TOF = 230 h(-1)) and stability in catalyzing formic acid dehydrogenation and hydrogen production in water at 50 °C without any additives.

Ligand-Promoted Rh(III)-Catalyzed Coupling of Aryl C-H Bonds with Arylboron Reagents.

PubMed

Wang, Huai-Wei; Cui, Pei-Pei; Lu, Yi; Sun, Wei-Yin; Yu, Jin-Quan

2016-04-15

Rhodium(III)-catalyzed C-H arylation of arenes with phenylboronic acid pinacol esters has been achieved using a readily removable N-pentafluorophenylbenzamide directing group for the first time. The use of a bidentate phosphine ligand (Binap) significantly increased the yield of the cross-coupling of C-H bonds with organoboron reagents.

Palladium-Catalyzed Asymmetric Allylic Alkylation of Electron-Deficient Pyrroles with Meso Electrophiles

PubMed Central

Osipov, Maksim; Dong, Guangbin

2012-01-01

Pyrroles can serve as competent nucleophiles with meso electrophiles in the Pd-catalyzed asymmetric allylic alkylation. The products from this transformation were obtained as a single regio- and diastereomer in high yield and enantiopurity. A nitropyrrole-containing nucleoside analogue was synthesized in 7 steps to demonstrate the synthetic utility of this transformation. PMID:22506671

Regio- and enantioselective palladium-catalyzed allylic alkylation of nitromethane with monosubstituted allyl substrates: synthesis of (R)-rolipram and (R)-baclofen.

PubMed

Yang, Xiao-Fei; Ding, Chang-Hua; Li, Xiao-Hui; Huang, Jian-Qiang; Hou, Xue-Long; Dai, Li-Xin; Wang, Pin-Jie

2012-10-19

The Pd-catalyzed asymmetric allylic alkylation (AAA) reaction of nitromethane with monosubstituted allyl substrates was realized for the first time to provide corresponding products in high yields with excellent regio- and enantioselectivities. The protocol was applied to the enantioselective synthesis of (R)-baclofen and (R)-rolipram.

Modular, Metal-Catalyzed Cycloisomerization Approach to Angularly Fused Polycyclic Aromatic Hydrocarbons and Their Oxidized Derivatives

PubMed Central

Thomson, Paul F.; Parrish, Damon; Pradhan, Padmanava; Lakshman, Mahesh K.

2015-01-01

Palladium-catalyzed cross-coupling reactions of 2-bromobenzaldehyde and 6-bromo-2,3-dimethoxybenzaldehyde with 4-methyl-1-naphthaleneboronic acid and acenaphthene-5-boronic acid gave corresponding o-naphthyl benzaldehydes. Corey–Fuchs olefination followed by reaction with n-BuLi led to various 1-(2-ethynylphenyl)naphthalenes. Cycloisomerization of individual 1-(2-ethynylphenyl)naphthalenes to various benzo[c]phenanthrene (BcPh) analogues was accomplished smoothly with catalytic PtCl2 in PhMe. In the case of 4,5-dihydrobenzo[l]acephenanthrylene, oxidation with DDQ gave benzo[l]acephenanthrylene. The dimethoxy-substituted benzo[c]phenanthrenes were demethylated with BBr3 and oxidized to the ortho-quinones with PDC. Reduction of these quinones with NaBH4 in THF/EtOH in an oxygen atmosphere gave the respective dihydrodiols. Exposure of the dihydrodiols to N-bromoacetamide in THF-H2O led to bromohydrins that were cyclized with Amberlite IRA 400 HO− to yield the series 1 diol epoxides. Epoxidation of the dihydrodiols with mCPBA gave the isomeric series 2 diol epoxides. All of the hydrocarbons as well as the methoxy-substituted ones were crystallized and analyzed by X-ray crystallography, and these data are compared to other previously studied BcPh derivatives. The methodology described is highly modular and can be utilized for the synthesis of a wide variety of angularly fused polycyclic aromatic hydrocarbons and their putative metabolites and/or other derivatives. PMID:26196673

Copper-catalyzed domino reactions for the synthesis of cyclic compounds.

PubMed

Liao, Qian; Yang, Xianghua; Xi, Chanjuan

2014-09-19

Copper-catalyzed domino reactions are one of the most useful strategies for the construction of various cyclic compounds. In this Synopsis, we mainly focus on the latest advances in copper-catalyzed cross-coupling or addition-initiated domino reactions in the synthesis of cyclic compounds, including double alkenylation of N- or S-nucleophiles, alkenylation or alkynlation followed by cyclization of amides or amines, addition and cyclization of heteroallenes affording heterocycles, and coupling and cyclization of 1,3-dicarbonyl compounds toward heterocycles.

Copper-catalyzed trifluoromethylthiolation of aryl halides with diverse directing groups.

PubMed

Xu, Jiabin; Mu, Xin; Chen, Pinhong; Ye, Jinxing; Liu, Guosheng

2014-08-01

The expansion of cross-coupling components in Cu-catalyzed C-X bond forming reactions have received much attention recently. A novel Cu-catalyzed trifluoromethylthiolation of aryl bromides and iodides with the assistance of versatile directing groups such as pyridyl, methyl ester, amide, imine and oxime was reported. CuBr was used as the catalyst, and 1,10-phenanthroline as the ligand. By changing the solvent from acetonitrile to DMF, the coupling process could even take place at room temperature.

Recent Developments in C-H Activation for Materials Science in the Center for Selective C-H Activation.

PubMed

Zhang, Junxiang; Kang, Lauren J; Parker, Timothy C; Blakey, Simon B; Luscombe, Christine K; Marder, Seth R

2018-04-16

Abstract : Organic electronics is a rapidly growing field driven in large part by the synthesis of ∏-conjugated molecules and polymers. Traditional aryl cross-coupling reactions such as the Stille and Suzuki have been used extensively in the synthesis of ∏-conjugated molecules and polymers, but the synthesis of intermediates necessary for traditional cross-couplings can include multiple steps with toxic and hazardous reagents. Direct arylation through C-H bond activation has the potential to reduce the number of steps and hazards while being more atom-economical. Within the Center for Selective C-H Functionalization (CCHF), we have been developing C-H activation methodology for the synthesis of ∏-conjugated materials of interest, including direct arylation of difficult-to-functionalize electron acceptor intermediates and living polymerization of ∏-conjugated polymers through C-H activation.

Synthesis and characterization of monoisomeric 1,8,15,22-substituted (A3B and A2B2) phthalocyanines and phthalocyanine-fullerene dyads.

PubMed

Ranta, Jenni; Kumpulainen, Tatu; Lemmetyinen, Helge; Efimov, Alexander

2010-08-06

Synthesis and characterization of three phthalocyanine-fullerene (Pc-C(60)) dyads, corresponding monoisomeric phthalocyanines (Pc), and building blocks, phthalonitriles, are described. Six novel bisaryl phthalonitriles were prepared by the Suzuki-Miyaura coupling reaction from trifluoromethanesulfonic acid 2,3-dicyanophenyl ester and various oxaborolanes. Two phthalonitriles were selected for the synthesis of A(3)B- and A(2)B(2)-type phthalocyanines. Phthalonitrile 4 has a bulky 3,5-di-tert-butylphenyl substituent at the alpha-phthalo position, which forces only one regioisomer to form and greatly increases the solubility of phthalocyanine. Phthalonitrile 8 has a 3-phenylpropanol side chain at the alpha-position making further modifications of the side group possible. Synthesized monoisomeric A(3)B- and A(2)B(2)-type phthalocyanines are modified by attachment of malonic residues. Finally, fullerene is covalently linked to phthalocyanine with one or two malonic bridges to produce Pc-C(60) dyads. Due to the monoisomeric structure and increased solubility of phthalocyanines, the quality of NMR spectra of the compounds is enhanced significantly, making detailed NMR analysis of the structures possible. The synthesized dyads have different orientations of phthalocyanine and fullerene, which strongly influence the electron transfer (ET) from phthalocyanine to fullerene moiety. Fluorescence quenchings of the dyads were measured in both polar and nonpolar solvents, and in all cases, the quenching was more efficient in the polar environment. As expected, most efficient fluorescence quenching was observed for dyad 20b, with two linkers and phthalocyanine and fullerene in face-to-face orientation.

A recyclable palladium-catalyzed synthesis of 2-methylene-2,3-dihydrobenzofuran-3-ols by cycloisomerization of 2-(1-hydroxyprop-2-ynyl)phenols in ionic liquids.

PubMed

Mancuso, Raffaella; Gabriele, Bartolo

2013-09-04

A recyclable palladium-catalyzed synthesis of 2-methylene-2,3-dihydrobenzofuran-3-ols 2 by heterocyclization of 2-(1-hydroxyprop-2-ynyl)phenols 1 in an ionic liquid medium (BmimBF4) is presented. The process takes place under relatively mild conditions (100 °C, 5 h) in the presence of catalytic amounts (2 mol %) of PdI2 in conjunction with KI (5 equiv with respect to PdI2) and an organic base, such as morpholine (1 equiv with respect to 1), to give 2 in high yields (70%-86%). The PdI2-KI catalytic system could be recycled up to six times without appreciable loss of activity. Moreover, products 2 could be easily converted in a one-pot fashion into 2-hydroxymethylbenzofurans 3 (52%-71%, based on 1) and 2-methoxymethylbenzofurans 4 (52%-80%, based on 1) by acid-catalyzed allylic isomerization or allylic nucleophilic substitution.

Triphenylphosphine as Ligand for Room Temperature Ni(0)-Catalyzed Cross-Coupling Reactions of Aryl Chlorides with Arylboronic Acids

PubMed Central

Tang, Zhen-Yu; Hu, Qiao-Sheng

2008-01-01

Room temperature Ni(0)-catalyzed cross-coupling reactions of deactivated aryl chlorides with arylboronic acids with inexpensive triphenylphosphine (PPh3) as a supporting ligand have been accomplished in good to excellent yields. Air-stable Ni(PPh3)2Cl2 has also been established as catalyst precursor and highly active nickel catalysts were obtained when the reduction of Ni(PPh3)2Cl2 with n-BuLi was carried out in presence of an aryl chloride. PMID:16497011

Iron-Catalyzed Enantioselective Cross-Coupling Reactions of α-Chloroesters with Aryl Grignard Reagents.

PubMed

Jin, Masayoshi; Adak, Laksmikanta; Nakamura, Masaharu

2015-06-10

The first iron-catalyzed enantioselective cross-coupling reaction between an organometallic compound and an organic electrophile is reported. Synthetically versatile racemic α-chloro- and α-bromoalkanoates were coupled with aryl Grignard reagents in the presence of catalytic amounts of an iron salt and a chiral bisphosphine ligand, giving the products in high yields with acceptable and synthetically useful enantioselectivities (er up to 91:9). The produced α-arylalkanoates were readily converted to the corresponding α-arylalkanoic acids with high optical enrichment (er up to >99:1) via simple deprotections/recrystallizations. The results of radical probe experiments are consistent with a mechanism that involves the formation of an alkyl radical intermediate, which undergoes subsequent enantioconvergent arylation in an intermolecular manner. The developed asymmetric coupling offers not only facile and practical access to various chiral α-arylalkanoic acid derivatives, which are of significant pharmaceutical importance, but also a basis of controlling enantioselectivity in an iron-catalyzed organometallic transformation.

Monitoring chemical reactions by low-field benchtop NMR at 45 MHz: pros and cons.

PubMed

Silva Elipe, Maria Victoria; Milburn, Robert R

2016-06-01

Monitoring chemical reactions is the key to controlling chemical processes where NMR can provide support. High-field NMR gives detailed structural information on chemical compounds and reactions; however, it is expensive and complex to operate. Conversely, low-field NMR instruments are simple and relatively inexpensive alternatives. While low-field NMR does not provide the detailed information as the high-field instruments as a result of their smaller chemical shift dispersion and the complex secondary coupling, it remains of practical value as a process analytical technology (PAT) tool and is complimentary to other established methods, such as ReactIR and Raman spectroscopy. We have tested a picoSpin-45 (currently under ThermoFisher Scientific) benchtop NMR instrument to monitor three types of reactions by 1D (1) H NMR: a Fischer esterification, a Suzuki cross-coupling, and the formation of an oxime. The Fischer esterification is a relatively simple reaction run at high concentration and served as proof of concept. The Suzuki coupling is an example of a more complex, commonly used reaction involving overlapping signals. Finally, the oxime formation involved a reaction in two phases that cannot be monitored by other PAT tools. Here, we discuss the pros and cons of monitoring these reactions at a low-field of 45 MHz by 1D (1) H NMR. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Palladium-bacterial cellulose membranes for fuel cells.

PubMed

Evans, Barbara R; O'Neill, Hugh M; Malyvanh, Valerie P; Lee, Ida; Woodward, Jonathan

2003-07-01

Bacterial cellulose is a versatile renewable biomaterial that can be used as a hydrophilic matrix for the incorporation of metals into thin, flexible, thermally stable membranes. In contrast to plant cellulose, we found it catalyzed the deposition of metals within its structure to generate a finely divided homogeneous catalyst layer. Experimental data suggested that bacterial cellulose possessed reducing groups capable of initiating the precipitation of palladium, gold, and silver from aqueous solution. Since the bacterial cellulose contained water equivalent to at least 200 times the dry weight of the cellulose, it was dried to a thin membranous structure suitable for the construction of membrane electrode assemblies (MEAs). Results of our study with palladium-cellulose showed that it was capable of catalyzing the generation of hydrogen when incubated with sodium dithionite and generated an electrical current from hydrogen in an MEA containing native cellulose as the polyelectrolyte membrane (PEM). Advantages of using native and metallized bacterial cellulose membranes in an MEA over other PEMs such as Nafion 117 include its higher thermal stability to 130 degrees C and lower gas crossover.

Redox-Controlled Olefin (Co)Polymerization Catalyzed by Ferrocene-Bridged Phosphine-Sulfonate Palladium Complexes.

PubMed

Chen, Min; Yang, Bangpei; Chen, Changle

2015-12-14

The facile and reversible interconversion between neutral and oxidized forms of palladium complexes containing ferrocene-bridged phosphine sulfonate ligands was demonstrated. The activity of these palladium complexes could be controlled using redox reagents during ethylene homopolymerization, ethylene/methyl acrylate copolymerization, and norbornene oligomerization. Specifically in norbornene oligomerization, the neutral complexes were not active at all whereas the oxidized counterparts showed appreciable activity. In situ switching between the neutral and oxidized forms resulted in an interesting "off" and "on" behavior in norbornene oligomerization. This work provides a new strategy to control the olefin polymerization process. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Iron- and cobalt-catalyzed arylation of azetidines, pyrrolidines, and piperidines with Grignard reagents.

PubMed

Barré, Baptiste; Gonnard, Laurine; Campagne, Rémy; Reymond, Sébastien; Marin, Julien; Ciapetti, Paola; Brellier, Marie; Guérinot, Amandine; Cossy, Janine

2014-12-05

Iron- and cobalt-catalyzed cross-couplings between iodo-azetidines, -pyrrolidines, -piperidines, and Grignard reagents are disclosed. The reaction is efficient, cheap, chemoselective and tolerates a large variety of (hetero)aryl Grignard reagents.

Excellent deep-blue emitting materials based on anthracene derivatives for non-doped organic light-emitting diodes

NASA Astrophysics Data System (ADS)

Wang, Zhiqiang; Liu, Wei; Xu, Chen; Ji, Baoming; Zheng, Caijun; Zhang, Xiaohong

2016-08-01

Two deep-blue emitting materials 2-tert-butyl-9,10-bis(3,5-diphenylphenyl)anthracene (An-1) and 2-tert-butyl-9,10-bis(3,5-diphenylbiphenyl-4‧-yl)anthracene (An-2) were successfully synthesized by the Pd-catalyzed Suzuki coupling reaction. Both of these compounds have high thermal stabilities and show strong deep-blue emission as solid-state film as well as in n-hexane solution. Two non-doped electroluminescent devices employing An-1 and An-2 as emitting layers were fabricated by vacuum vapor deposition. These devices exhibited highly efficient and stable deep-blue emission with high color purity. The CIE coordinate and maximum EQE of An-1 based device are 4.2% and (0.16, 0.06), respectively. Device based on An-2 achieved a maximum EQE of 4.0% and a CIE coordinate of (0.16, 0.10).

Linear scaling relationships and volcano plots in homogeneous catalysis – revisiting the Suzuki reaction† †Electronic supplementary information (ESI) available: Detailed derivation of the linear scaling relationships and construction of the volcano plots as well as comparisons of computed values using PBE0-dDsC and M06 functionals is included. See DOI: 10.1039/c5sc02910d Click here for additional data file.

PubMed Central

Busch, Michael; Wodrich, Matthew D.

2015-01-01

Linear free energy scaling relationships and volcano plots are common tools used to identify potential heterogeneous catalysts for myriad applications. Despite the striking simplicity and predictive power of volcano plots, they remain unknown in homogeneous catalysis. Here, we construct volcano plots to analyze a prototypical reaction from homogeneous catalysis, the Suzuki cross-coupling of olefins. Volcano plots succeed both in discriminating amongst different catalysts and reproducing experimentally known trends, which serves as validation of the model for this proof-of-principle example. These findings indicate that the combination of linear scaling relationships and volcano plots could serve as a valuable methodology for identifying homogeneous catalysts possessing a desired activity through a priori computational screening. PMID:28757966

Copper-catalyzed direct synthesis of diaryl 1,2-diketones from aryl iodides and propiolic acids.

PubMed

Min, Hongkeun; Palani, Thiruvengadam; Park, Kyungho; Hwang, Jinil; Lee, Sunwoo

2014-07-03

Benzil derivatives such as diaryl 1,2-diketones are synthesized via the direct decarboxylative coupling reaction of aryl propiolic acids and their oxidation. The optimized conditions are that the reaction of aryl propiolic acids and aryl iodides is conducted at 140 °C for 6 h in the presence of 10 mol % CuI/Cu(OTf)2 and Cs2CO3, after which HI (aq) is added and further reacted. The method shows good functional group tolerance toward ester, aldehyde, cyano, and nitro groups. In addition, symmetrical diaryl 1,2-diketones are obtained from aryl iodides and propiolic acid in the presence of palladium and copper catalysts.

Transition metal catalyzed borylation of functional π-systems

PubMed Central

SHINOKUBO, Hiroshi

2014-01-01

Borylated functional π-systems are useful building blocks to enable efficient synthesis of novel molecular architectures with beautiful structures, intriguing properties and unique functions. Introduction of boronic ester substituents to a variety of extended π-systems can be achieved through either iridium-catalyzed direct C–H borylation or the two-step procedure via electrophilic halogenation followed by palladium-catalyzed borylation. This review article focuses on our recent progress on borylation of large π-conjugated systems such as porphyrins, perylene bisimides, hexabenzocoronenes and dipyrrins. PMID:24492644

A new route to methyl (R,E)-(-)-tetradeca-2,4,5-trienoate (pheromone of Acanthoscelides obtectus) utilizing a palladium-catalyzed asymmetric allene formation reaction.

PubMed

Ogasawara, Masamichi; Nagano, Takashi; Hayashi, Tamio

2005-07-08

[reaction: see text] A formal total synthesis of the sex attractant of male dried bean beetle, methyl (R,E)-(-)-tetradeca-2,4,5-trienoate, was achieved by a new efficient route utilizing the Pd-catalyzed asymmetric allene synthesis reaction. It was found that the atropisomeric biaryl bisphosphine (R)-segphos showed better enantioselectivity than (R)-binap in the Pd-catalyzed reaction for preparing alkyl-substituted axially chiral allenes.

Hydrophobic and hydrophilic nanosheet catalysts with high catalytic activity and recycling stability through control of the outermost ligand

NASA Astrophysics Data System (ADS)

Ko, Younji; Kim, Donghee; Kwon, Cheong Hoon; Cho, Jinhan

2018-04-01

In this study, we introduce hydrophobic and hydrophilic graphene oxide nanosheet (GON) catalysts prepared by consecutive ligand replacement of hydrophobically stabilized magnetic and catalytic nanoparticles (NPs); it exhibits high catalytic activity, fast magnetic response, and good dispersion in both nonpolar and aqueous media, allowing high loading amount of magnetic and catalytic NPs onto GON sheets. More specifically, these GON catalysts showed a high product yield of 66-99% and notable recyclability (93% of the initial product yield after 10 reaction cycles) in a Suzuki-Miyaura reaction in nonpolar media, outperforming the performance of the conventional hydrophilic GON catalysts. Additional coating of a hydrophilic layer onto GON catalysts also showed the notable performance (product yield ∼99%) in catalytic reactions performed in aqueous media. Given that ligand-controlled catalytic NPs adsorbed onto 2D nanosheets can be used as hydrophobic and hydrophilic stabilizers as well as catalysts, our approach can provide a tool for developing and designing 2D-nanosheet catalysts with high performance in nonpolar and polar media.

Enhanced Colorimetric Immunoassay Accompanying with Enzyme Cascade Amplification Strategy for Ultrasensitive Detection of Low-Abundance Protein

PubMed Central

Gao, Zhuangqiang; Hou, Li; Xu, Mingdi; Tang, Dianping

2014-01-01

Methods based on enzyme labels have been developed for colorimetric immunoassays, but most involve poor sensitivity and are unsuitable for routine use. Herein, we design an enhanced colorimetric immunoassay for prostate-specific antigen (PSA) coupling with an enzyme-cascade-amplification strategy (ECAS-CIA). In the presence of target PSA, the labeled alkaline phosphatase on secondary antibody catalyzes the formation of palladium nanostructures, which catalyze 3,3′,5,5′-tetramethylbenzidine-H2O2 system to produce the colored products, thus resulting in the signal cascade amplification. Results indicated that the ECAS-CIA presents good responses toward PSA, and allows detection of PSA at a concentration as low as 0.05 ng mL−1. Intra- and inter-assay coefficients of variation are below 9.5% and 10.7%, respectively. Additionally, the methodology is validated for analysis of clinical serum specimens with consistent results obtained by PSA ELISA kit. Importantly, the ECAS-CIA opens a new horizon for protein diagnostics and biosecurity. PMID:24509941

Controlling site selectivity in Pd-catalyzed oxidative cross-coupling reactions.

PubMed

Lyons, Thomas W; Hull, Kami L; Sanford, Melanie S

2011-03-30

This paper presents a detailed investigation of the factors controlling site selectivity in the Pd-mediated oxidative coupling of 1,3-disubstituted and 1,2,3-trisubstituted arenes (aryl-H) with cyclometalating substrates (L~C-H). The influence of both the concentration and the steric/electronic properties of the quinone promoter are studied in detail. In addition, the effect of steric/electronic modulation of the carboxylate ligand is discussed. Finally, we demonstrate that substitution of the carboxylate for a carbonate X-type ligand leads to a complete reversal in site selectivity for many arene substrates. The origins of these trends in site selectivity are discussed in the context of the mechanism of Pd-catalyzed oxidative cross-coupling.

Stable optical oxygen sensing materials based on click-coupling of fluorinated platinum(II) and palladium(II) porphyrins—A convenient way to eliminate dye migration and leaching

PubMed Central

Koren, Klaus; Borisov, Sergey M.; Klimant, Ingo

2012-01-01

Nucleophilic substitution of the labile para-fluorine atoms of 2,3,4,5,6-pentafluorophenyl groups enables a click-based covalent linkage of an oxygen indicator (platinum(II) or palladium(II) 5,10,15,20-meso-tetrakis-(2,3,4,5,6-pentafluorophenyl)-porphyrin) to the sensor matrix. Copolymers of styrene and pentafluorostyrene are chosen as polymeric materials. Depending on the reaction conditions either soluble sensor materials or cross-linked microparticles are obtained. Additionally, we prepared Ormosil-based sensors with linked indicator, which showed very high sensitivity toward oxygen. The effect of covalent coupling on sensor characteristics, stability and photophysical properties is studied. It is demonstrated that leaching and migration of the dye are eliminated in the new materials but excellent photophysical properties of the indicators are preserved. PMID:23576845

Palladium- and Copper-Catalyzed Arylation of Carbon-Hydrogen Bonds

PubMed Central

Daugulis, Olafs; Do, Hien-Quang; Shabashov, Dmitry

2010-01-01

The transition-metal-catalyzed functionalization of C-H bonds is a powerful method for generating carbon-carbon bonds. Although significant advances to this field have been reported during the last decade, many challenges remain. First, most of the methods are substrate-specific and thus cannot be generalized. Second, conversions of unactivated (i.e. not benzylic or alpha to heteroatom) sp3 C–H bonds to C–C bonds are rare, with most examples limited to t-butyl groups—a conversion that is inherently simple because there are no β-hydrogens that can be eliminated. Finally, the palladium, rhodium, and ruthenium catalysts routinely used for the conversion of C–H bonds to C–C bonds are expensive. Catalytically active metals that are cheaper and less exotic (e.g. copper, iron, and manganese) are rarely used. This Account describes our attempts to provide solutions to these three problems. We have developed a general method for directing-group-containing arene arylation by aryl iodides. Using palladium acetate as the catalyst, we arylated anilides, benzamides, benzoic acids, benzylamines, and 2-substituted pyridine derivatives under nearly identical conditions. We have also developed a method for the palladium-catalyzed auxiliary-assisted arylation of unactivated sp3 C–H bonds. This procedure allows for the β-arylation of carboxylic acid derivatives and the γ-arylation of amine derivatives. Furthermore, copper catalysis can be used to mediate the arylation of acidic arene C–H bonds (i.e. those with pKa values <35 in DMSO). Using a copper iodide catalyst in combination with a base and a phenanthroline ligand, we successfully arylated electron-rich and electron-deficient heterocycles and electron-poor arenes possessing at least two electron-withdrawing groups. The reaction exhibits unusual regioselectivity: arylation occurs at the most hindered position. This copper-catalyzed method supplements the well-known C–H activation/borylation methodology, in which functionalization usually occurs at the least hindered position. We also describe preliminary investigations to determine the mechanisms of these transformations. We anticipate that other transition metals, including iron, nickel, cobalt, and silver, will also be able to facilitate deprotonation/arylation reaction sequences. PMID:19552413

Palladium- and copper-catalyzed arylation of carbon-hydrogen bonds.

PubMed

Daugulis, Olafs; Do, Hien-Quang; Shabashov, Dmitry

2009-08-18

The transition-metal-catalyzed functionalization of C-H bonds is a powerful method for generating carbon-carbon bonds. Although significant advances to this field have been reported during the past decade, many challenges remain. First, most of the methods are substrate-specific and thus cannot be generalized. Second, conversions of unactivated (i.e., not benzylic or alpha to heteroatom) sp(3) C-H bonds to C-C bonds are rare, with most examples limited to t-butyl groups, a conversion that is inherently simple because there are no beta-hydrogens that can be eliminated. Finally, the palladium, rhodium, and ruthenium catalysts routinely used for the conversion of C-H bonds to C-C bonds are expensive. Catalytically active metals that are cheaper and less exotic (e.g., copper, iron, and manganese) are rarely used. This Account describes our attempts to provide solutions to these three problems. We have developed a general method for directing-group-containing arene arylation by aryl iodides. Using palladium acetate as the catalyst, we arylated anilides, benzamides, benzoic acids, benzylamines, and 2-substituted pyridine derivatives under nearly identical conditions. We have also developed a method for the palladium-catalyzed auxiliary-assisted arylation of unactivated sp(3) C-H bonds. This procedure allows for the beta-arylation of carboxylic acid derivatives and the gamma-arylation of amine derivatives. Furthermore, copper catalysis can be used to mediate the arylation of acidic arene C-H bonds (i.e., those with pK(a) values <35 in DMSO). Using a copper iodide catalyst in combination with a base and a phenanthroline ligand, we successfully arylated electron-rich and electron-deficient heterocycles and electron-poor arenes possessing at least two electron-withdrawing groups. The reaction exhibits unusual regioselectivity: arylation occurs at the most hindered position. This copper-catalyzed method supplements the well-known C-H activation/borylation methodology, in which functionalization usually occurs at the least hindered position. We also describe preliminary investigations to determine the mechanisms of these transformations. We anticipate that other transition metals, including iron, nickel, cobalt, and silver, will also be able to facilitate deprotonation/arylation reaction sequences.

Homogeneous Palladium-Catalyzed Transfer Hydrogenolysis of Benzylic Alcohols Using Formic Acid as Reductant.

PubMed

Ciszek, Benjamin; Fleischer, Ivana

2018-04-12

Herein we report the first homogeneous palladium-based transfer hydrogenolysis of benzylic alcohols using an in situ formed palladium-phosphine complex and formic acid as reducing agent. The reaction requires a catalyst loading as low as only 1 mol% of palladium and just a slight excess of reductant to obtain the deoxygenated alkylarenes in good to excellent yields. Besides demonstrating the broad applicability for primary, secondary and tertiary benzylic alcohols, a reaction intermediate could be identified. Additionally, it could be shown that partial oxidation of the applied phosphine ligand was beneficial for the course of the reaction, presumably by stabilizing the active catalyst. Reaction profiles and catalyst poisoning experiments were used to characterize the catalyst, the results indicate a homogeneous metal complex as active species. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

New synthesis and antiparasitic activity of model 5-aryl-1-methyl-4-nitroimidazoles.

PubMed

Saadeh, Haythem A; Mosleh, Ibrahim M; El-Abadelah, Mustafa M

2009-07-27

A number of 5-aryl-1-methyl-4-nitroimidazoles 5a-f have been synthesized in good yields by the Suzuki coupling reaction between 5-chloro-1-methyl-4-nitroimidazole (3) and arylboronic acids 4a-f, aided by dichlorobis-(triphenylphosphine)palladium(II), K(2)CO(3, )and tetrabutylammonium bromide in water at 70-80 degrees C. Compounds 5a-f were characterized by elemental analysis, NMR and MS spectral data. On the basis of in vitro screening data, 5-(3-chlorophenyl)-1-methyl-4-nitro-1H-imidazole (5f) exhibited potent lethal activity against Entamoeba histolytica and Giardia intestinalis with IC(50) = 1.47 microM/mL, a value lower by a factor of two than that of the standard drug, metronidazole. The boosted activity of 5f was not accompanied by any increased cytotoxicity.The rest of the series also exhibited potent antiparasitic activity with IC(50 ) values in the 1.72-4.43 microM/mL range. The cytotoxicity of the derivatives 5c and 5e was increased compared to the precursor compound, metronidazole, although they remain non-cytotoxic at concentrations much higher than the antiparasitic concentration of the two derivatives.

An Operationally Simple Sonogashira Reaction for an Undergraduate Organic Chemistry Laboratory Class

ERIC Educational Resources Information Center

Cranwell, Philippa B.; Peterson, Alexander M.; Littlefield, Benjamin T. R.; Russell, Andrew T.

2015-01-01

An operationally simple, reliable, and cheap Sonogashira reaction suitable for an undergraduate laboratory class that can be completed within a day-long (8 h) laboratory session has been developed. Cross-coupling is carried out between 2-methyl-3-butyn-2-ol and various aryl iodides using catalytic amounts of bis(triphenylphosphine)palladium(II)…

Iron-catalyzed oxidative biaryl cross-couplings via mixed diaryl titanates: significant influence of the order of combining aryl Grignard reagents with titanate.

PubMed

Liu, Kun Ming; Wei, Juan; Duan, Xin Fang

2015-03-18

The mixed diaryl titanates were used for the first time to modify the reactivity of two aryl Grignard reagents. Two titanate intermediates, Ar[Ar'Ti(OR)3]MgX and Ar'[ArTi(OR)3]MgX, formed via alternating the sequence of combining Grignard reagents with ClTi(OR)3 showed a significant reactivity difference. Taking advantage of such different reactivity, two highly structurally similar aryl groups could be facilely assembled through iron-catalyzed oxidative cross-couplings using oxygen as the oxidant.

Pd-Catalyzed regioselective intramolecular dehydrogenative C-5 cross coupling in an N-substituted pyrrole-azole system.

PubMed

Tripathi, Krishna N; Ray, Devalina; Singh, Ravi P

2017-12-06

Functionalized polycyclic pyrrole-azole structures possessing fused six membered and seven membered rings were directly synthesized via ligand-enabled, Pd-catalyzed, site selective, intramolecular cross couplings of N-substituted pyrrole-azoles. C5-H activation in the presence of a reactive C2-H remains a challenge that needs to be addressed and this was targeted to be resolved through the present approach by specifically generating the cyclized products with 83-100% selectivity. The featured methodology provides a novel disconnection for the synthesis of pyrrole containing alkaloids and medicinal compounds.

A Three-Dimensional Capsule-Like Carbon Nanocage as a Novel Segment Model of Capped Zigzag [12,0] Carbon Nanotubes: Synthesis, Characterization, and Complexation with C70.

PubMed

Du, Pingwu

2018-05-17

Herein we report the synthesis, photophysical, and supramolecular properties of a novel three-dimensional capsule-like hexa-peri-hexabenzocoronene (HBC)-containing carbon nanocage, tripodal-[2]HBC, which represents the first synthetic model of the capped zigzag [12,0] carbon nanotubes (CNTs). Tripodal-[2]HBC was achieved by rationally designed palladium-catalyzed coupling of triborylhexabenzocoronene and L-shaped cyclohexane units, followed by nickel-mediated C-Br/C-Br coupling and the subsequent aromatization of the cyclohexane moieties. The physical properties of tripodal-[2]HBC and its supramolecular host-guest interaction with C70 were further studied by UV-vis and fluorescence spectroscopy. Theoretical calculations reveal that the strain energy of tripodal-[2]HBC is as high as 55.2 kcal mol-1. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Palladium-Catalyzed Direct C–H Arylation of Cyclic Enaminones with Aryl Iodides

PubMed Central

Yu, Yi-Yun; Bi, Lei

2013-01-01

A ligand-free method for the Pd-catalyzed direct arylation of cyclic enaminones using aryl iodides was developed. This method can be applied to a wide range of cyclic enaminones and aryl iodides with excellent C5-regioselectivity. Using widely available aryl iodides, the generality of this transformation provides easy access to a variety of 3-arylpiperidine structural motifs. PMID:23750615

Indole synthesis by palladium-catalyzed tandem allylic isomerization - furan Diels-Alder reaction.

PubMed

Xu, Jie; Wipf, Peter

2017-08-30

A Pd(0)-catalyzed elimination of an allylic acetate generates a π-allyl complex that is postulated to initiate a novel intramolecular Diels-Alder cycloaddition to a tethered furan (IMDAF). Under the reaction conditions, this convergent, microwave-accelerated cascade process provides substituted indoles in moderate to good yields after Pd-hydride elimination, aromatization by dehydration, and in situ N-Boc cleavage.

Modeling of hydrogen/deuterium dynamics and heat generation on palladium nanoparticles for hydrogen storage and solid-state nuclear fusion.

PubMed

Tanabe, Katsuaki

2016-01-01

We modeled the dynamics of hydrogen and deuterium adsorbed on palladium nanoparticles including the heat generation induced by the chemical adsorption and desorption, as well as palladium-catalyzed reactions. Our calculations based on the proposed model reproduce the experimental time-evolution of pressure and temperature with a single set of fitting parameters for hydrogen and deuterium injection. The model we generated with a highly generalized set of formulations can be applied for any combination of a gas species and a catalytic adsorbent/absorbent. Our model can be used as a basis for future research into hydrogen storage and solid-state nuclear fusion technologies.

Consecutive three-component synthesis of (hetero)arylated propargyl amides by chemoenzymatic aminolysis-Sonogashira coupling sequence.

PubMed

Hassan, Sidra; Ullrich, Anja; Müller, Thomas J J

2015-02-07

A novel chemoenzymatic three-component synthesis of (hetero)arylated propargyl amides in good yields based upon Novozyme® 435 (Candida antarctica lipase B (CAL-B)) catalyzed aminolysis of methyl carboxylates followed by Sonogashira coupling with (hetero)aryliodides in a consecutive one-pot fashion has been presented. This efficient methodology can be readily concatenated with a CuAAC (Cu catalyzed alkyne azide cycloaddition) as a third consecutive step to furnish 1,4-disubstituted 1,2,3-triazole ligated arylated propargyl amides. This one-pot process can be regarded as a transition metal catalyzed sequence that takes advantage of the copper source still present from the cross-coupling step.

A General Synthetic Route to Polycyclic Aromatic Dicarboximides by Palladium-Catalyzed Annulation Reaction.

PubMed

Shoyama, Kazutaka; Mahl, Magnus; Seifert, Sabine; Würthner, Frank

2018-03-20

Here we report a general method for the synthesis of polycyclic aromatic dicarboximides (PADIs) by palladium-catalyzed annulation of naphthalene dicarboximide to different types of aromatic substrates. Reaction conditions were optimized by systematic variation of ligand, solvent, and additive. It was shown that solvent has a decisive effect on the yield of the reaction products, and thus 1-chloronaphthalene as solvent afforded the highest yield. By applying the optimized reaction conditions, a broad series of planar carbo- and heterocycle containing PADIs were synthesized in up to 97% yield. Moreover, this approach could be applied to curved aromatic scaffold to achieve the respective bowl-shaped PADI. Two-fold annulation was accomplished by employing arene diboronic esters, affording polycyclic aromatic bis(dicarboximides). The optical and electrochemical properties of this broad series of PADIs were explored as well.

Design, Synthesis and Optoelectronic Properties of Unsymmetrical Oxadiazole Based Indene Substituted Derivatives as Deep Blue Fluoroscent Materials.

PubMed

Belavagi, Ningaraddi S; Deshapande, Narahari; Pujar, G H; Wari, M N; Inamdar, S R; Khazi, Imtiyaz Ahmed M

2015-09-01

A series of novel unsymmetrically substituted indene-oxadiazole derivatives (3a-f) have been designed and synthesized by employing palladium catalysed Suzuki cross coupling reaction in high yields. The structural integrity of all the novel compounds was established by (1)H, (13)C NMR and LC/MS analysis. These compounds are amorphous in nature and are remarkably stable to long term storage under ambient conditions. The optoelectronic properties have been studied in detail using UV-Vis absorption and Fluorescence spectroscopy. All compounds emit intense blue to green-blue fluoroscence with high quantum yields. Time resolved measurments have shown life times in the range of 1.28 to 4.51 ns. The density functional theory (DFT) calculations were carried out for all the molecules to understand their structure-property relationships. Effect of concentration studies has been carried out in different concentrations for both absorption and emission properties and from this we have identified the optimized fluoroscence concentrations for all these compounds. The indene substituted anthracene-oxadiazole derivative (3f) showed significant red shift (λmax (emi) = 490 nm) and emits intense green-blue fluoroscence with largest stokes shift of 145 nm. This compound also exhibited highest fluoroscence life time (τ) of 4.51 ns, which is very close to the standard dye coumarin-540A (4.63 ns) and better than fluorescein-548 (4.10 ns). The results demonstrated that the novel unsymmetrical indene-substituted oxadiazole derivatives could play important role in organic optoelectronic applications, such as organic light-emitting diodes (OLEDs) or as models for investigating the fluorescent structure-property relationship of the indene-functionalized oxadiazole derivatives.

Palladium-catalyzed asymmetric quaternary stereocenter formation.

PubMed

Gottumukkala, Aditya L; Matcha, Kiran; Lutz, Martin; de Vries, Johannes G; Minnaard, Adriaan J

2012-05-29

An efficient palladium catalyst is presented for the formation of benzylic quaternary stereocenters by conjugate addition of arylboronic acids to a variety of β,β-disubstituted carbocyclic, heterocyclic, and acyclic enones. The catalyst is readily prepared from PdCl(2), PhBOX, and AgSbF(6), and provides products in up to 99% enantiomeric excess, with good yields. Based on this strategy, (-)-α-cuparenone has been prepared in only two steps. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Allylic aminations with hindered secondary amine nucleophiles catalyzed by heterobimetallic Pd-Ti complexes.

PubMed

Walker, Whitney K; Anderson, Diana L; Stokes, Ryjul W; Smith, Stacey J; Michaelis, David J

2015-02-06

Phosphinoamide-scaffolded heterobimetallic palladium-titanium complexes are highly effective catalysts for allylic aminations of allylic chlorides with hindered secondary amine nucleophiles. Three titanium-containing ligands are shown to assemble active catalysts in situ and enable catalysis at room temperature. A variety of sterically bulky secondary amines are efficiently allylated in high yields with as little as 1 mol % palladium catalyst. Piperidine and pyrrolidine products are also efficiently generated via intramolecular aminations with hindered amine nucleophiles.

Palladium-Catalyzed Anti-Markovnikov Oxidation of Allylic Amides to Protected β-Amino Aldehydes.

PubMed

Dong, Jia Jia; Harvey, Emma C; Fañanás-Mastral, Martín; Browne, Wesley R; Feringa, Ben L

2014-12-10

A general method for the preparation of N-protected β-amino aldehydes from allylic amines or linear allylic alcohols is described. Here the Pd(II)-catalyzed oxidation of N-protected allylic amines with benzoquinone is achieved in tBuOH under ambient conditions with excellent selectivity toward the anti-Markovnikov aldehyde products and full retention of configuration at the allylic carbon. The method shows a wide substrate scope and is tolerant of a range of protecting groups. Furthermore, β-amino aldehydes can be obtained directly from protected allylic alcohols via palladium-catalyzed autotandem reactions, and the application of this method to the synthesis of β-peptide aldehydes is described. From a mechanistic perspective, we demonstrate that tBuOH acts as a nucleophile in the reaction and that the initially formed tert-butyl ether undergoes spontaneous loss of isobutene to yield the aldehyde product. Furthermore, tBuOH can be used stoichiometrically, thereby broadening the solvent scope of the reaction. Primary and secondary alcohols do not undergo elimination, allowing the isolation of acetals, which subsequently can be hydrolyzed to their corresponding aldehyde products.

Development of A Concise Synthesis of (−)-Oseltamivir (Tamiflu®)

PubMed Central

Trost, Barry M.; Zhang, Ting

2011-01-01

We report a full account of our work towards the development of an eight-step synthesis of anti-influenza drug (−)-oseltamivir (Tamiflu®) from commercially available starting material. The final synthetic route proceeds with an overall yield of 30 %. Key transformations include a novel palladium-catalyzed asymmetric allylic alkylation reaction (Pd-AAA) as well as a rhodium-catalyzed chemo-, regio-, and stereoselective aziridination reaction. PMID:21365707

Push-pull quinoidal porphyrins.

PubMed

Smith, Martin J; Blake, Iain M; Clegg, William; Anderson, Harry L

2018-05-01

A family of push-pull quinoidal porphyrin monomers has been prepared from a meso-formyl porphyrin by bromination, thioacetal formation, palladium-catalyzed coupling with malononitrile and oxidation with DDQ. Attempts at extending this synthesis to a push-pull quinoidal/cumulenic porphyrin dimer were not successful. The crystal structures of the quinoidal porphyrins indicate that there is no significant contribution from singlet biradical or zwitterionic resonance forms. The crystal structure of an ethyne-linked porphyrin dimer shows that the torsion angle between the porphyrin units is only about 3°, in keeping with crystallographic results on related compounds, but contrasting with the torsion angle of about 35° predicted by computational studies. The free-base quinoidal porphyrin monomers form tightly π-stacked layer structures, despite their curved geometries and bulky aryl substituents.

Copper-Catalyzed γ-Selective and Stereospecific Allylic Cross-Coupling with Secondary Alkylboranes.

PubMed

Yasuda, Yuto; Nagao, Kazunori; Shido, Yoshinori; Mori, Seiji; Ohmiya, Hirohisa; Sawamura, Masaya

2015-06-26

The scope of the copper-catalyzed coupling reactions between organoboron compounds and allylic phosphates is expanded significantly by employing triphenylphosphine as a ligand for copper, allowing the use of secondary alkylboron compounds. The reaction proceeds with complete γ-E-selectivity and preferential 1,3-syn stereoselectivity. The reaction of γ-silicon-substituted allylic phosphates affords enantioenriched α-stereogenic allylsilanes. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

An Efficient Process for Pd-Catalyzed C–N Cross-Coupling Reactions of Aryl Iodides: Insight Into Controlling Factors

PubMed Central

Fors, Brett P.; Davis, Nicole R.; Buchwald, Stephen L.

2009-01-01

An investigation into Pd-catalyzed C–N cross-coupling reactions of aryl iodides is described. NaI is shown to have a significant inhibitory effect on these processes. By switching to a solvent system in which the iodide byproduct was insoluble, reactions of aryl iodides were accomplished with the same efficiencies as aryl chlorides and bromides. Using catalyst systems based on certain biarylphosphine ligands, aryl iodides were successfully reacted with an array of primary and secondary amines in high yields. Lastly, reactions of heteroarylamines and heteroaryliodides were also conducted in high yields. PMID:19348431

Formal Synthesis of (±)-Roseophilin

PubMed Central

Bitar, Abdallah Y.; Frontier, Alison J.

2009-01-01

A formal synthesis of (±)-roseophilin is described. Scandium(III)-catalyzed Nazarov cyclization of 2,5-disubstituted N-tosylpyrrole 19 gives a 5,5’-fused ketopyrrole, and ansa-bridge formation via π-allyl palladium macrocyclization gives 21. PMID:19053717

A Palladium-Catalyzed Method for the Synthesis of 2-(α-Styryl)-2,3-dihydroquinazolin-4-ones and 3-(α-Styryl)-3,4-dihydro-1,2,4-benzothiadiazine-1,1-dioxide: Access to 2-(α-Styryl)quinazolin-4(3H)-ones and 3-(α-Styryl)-1,2,4-benzothiadiazine-1,1-dioxides.

PubMed

Kundu, Priyanka; Mondal, Amrita; Chowdhury, Chinmay

2016-08-05

An efficient synthesis of 2-(α-styryl)-2,3-dihydroquinazolin-4-ones and 3-(α-styryl)-3,4-dihydro-1,2,4-benzothiadiazine-1,1-dioxides has been achieved in 39-94% yield through palladium-catalyzed cyclocondensation of aryl/vinyl iodides with allenamides 13-15 and 22, respectively. Base treatment of the N-tosylated products provides an easy access to 2-(α-styryl)quinazolin-4(3H)-ones and 3-(α-styryl)-1,2,4-benzothiadiazine-1,1-dioxides, hitherto unknown heterocycles. The method has been tested with phenyl substituted allenamides, applied for bis-heteroannulation, and used in the preparation of analogues of the natural product Luotonin F.

The Palladium-Catalyzed Aerobic Kinetic Resolution of Secondary Alcohols: Reaction Development, Scope, and Applications

PubMed Central

Ebner, David C.; Bagdanoff, Jeffrey T.; Ferreira, Eric M.; McFadden, Ryan M.; Caspi, Daniel D.; Trend, Raissa M.

2010-01-01

The first palladium-catalyzed enantioselective oxidation of secondary alcohols has been developed, utilizing the readily available diamine (−)-sparteine as chiral ligand and molecular oxygen as the stoichiometric oxidant. Mechanistic insights regarding the role of base and hydrogen bond donors have resulted in several improvements to the original system. Namely, addition of cesium carbonate and tert-butyl alcohol greatly enhances reaction rates, promoting rapid resolutions. The use of chloroform as solvent allows the use of ambient air as the terminal oxidant at 23 °C, resulting in enhanced catalyst selectivity. These improved reaction conditions have permitted the successful kinetic resolution of benzylic, allylic, and cyclopropyl secondary alcohols to high enantiomeric excess with good to excellent selectivity factors. This catalyst system has also been applied to the desymmetrization of meso-diols, providing high yields of enantioenriched hydroxyketones. PMID:19904777

Mechanistic Insights into Photocatalyzed Hydrogen Desorption from Palladium Surfaces Assisted by Localized Surface Plasmon Resonances.

PubMed

Spata, Vincent A; Carter, Emily A

2018-04-24

Nanoparticles synthesized from plasmonic metals can absorb low-energy light, producing an oscillation/excitation of their valence electron density that can be utilized in chemical conversions. For example, heterogeneous photocatalysis can be achieved within heterometallic antenna-reactor complexes (HMARCs), by coupling a reactive center at which a chemical reaction occurs to a plasmonic nanoparticle that acts as a light-absorbing antenna. For example, HMARCs composed of aluminum antennae and palladium (Pd) reactive centers have been demonstrated recently to catalyze selective hydrogenation of acetylene to ethylene. Here, we explore within a theoretical framework the rate-limiting step of hydrogen photodesorption from a Pd surface-crucial to achieving partial rather than full hydrogenation of acetylene-to understand the mechanism behind the photodesorption process within the HMARC assembly. To properly describe electronic excited states of the metal-molecule system, we employ embedded complete active space self-consistent field and n-electron valence state perturbation theory to second order within density functional embedding theory. The results of these calculations reveal that the photodesorption mechanism does not create a frequently invoked transient negative ion species but instead enhances population of available excited-state, low-barrier pathways that exhibit negligible charge-transfer character.

An emerging reactor technology for chemical synthesis: surface acoustic wave-assisted closed-vessel Suzuki coupling reactions.

PubMed

Kulkarni, Ketav; Friend, James; Yeo, Leslie; Perlmutter, Patrick

2014-07-01

In this paper we demonstrate the use of an energy-efficient surface acoustic wave (SAW) device for driving closed-vessel SAW-assisted (CVSAW), ligand-free Suzuki couplings in aqueous media. The reactions were carried out on a mmolar scale with low to ultra-low catalyst loadings. The reactions were driven by heating resulting from the penetration of acoustic energy derived from RF Raleigh waves generated by a piezoelectric chip via a renewable fluid coupling layer. The yields were uniformly high and the reactions could be executed without added ligand and in water. In terms of energy density this new technology was determined to be roughly as efficient as microwaves and superior to ultrasound. Crown Copyright © 2014. Published by Elsevier B.V. All rights reserved.

Stereoselective Vinylation of Aryl N-(2-Pyridylsulfonyl) Aldimines with 1-Alkenyl-1,1-Heterobimetallic Reagents

PubMed Central

Hussain, Nusrah; Hussain, Mahmud M.; Ziauddin, Muhammed; Triyawatanyu, Plengchat; Walsh, Patrick J.

2011-01-01

Vinylation of aryl N-(2-pyridylsulfonyl) aldimines with versatile 1-alkenyl-1,1-borozinc heterobimetallic reagents is disclosed. In situ hydroboration of air-stable B(pin)-alkynes followed by chemoselective transmetallation with dimethylzinc and addition to aldimines provides B(pin)-substituted allylic amines in 60–93% yield in a one-pot procedure. The addition step can be followed by either B–C bond oxidation to provide α-amino ketones (71–98% yield) or Suzuki cross-coupling to furnish trisubstituted 2-arylated (E)-allylic amines (51–73% yield). PMID:22085226

Development of second generation gold-supported palladium material with low-leaching and recyclable characteristics in aromatic amination.

PubMed

Al-Amin, Mohammad; Arai, Satoshi; Hoshiya, Naoyoki; Honma, Tetsuo; Tamenori, Yusuke; Sato, Takatoshi; Yokoyama, Mami; Ishii, Akira; Takeuchi, Masashi; Maruko, Tomohiro; Shuto, Satoshi; Arisawa, Mitsuhiro

2013-08-02

An improved process for the preparation of sulfur-modified gold-supported palladium material [SAPd, second generation] is presented. The developed preparation method is safer and generates less heat (aqueous Na2S2O8 and H2SO4) for sulfur fixation on a gold surface, and it is superior to the previous method of preparing SAPd (first generation), which requires the use of the more heat-generating and dangerous piranha solution (concentrated H2SO4 and 35% H2O2) in the sulfur fixation step. This safer and improved preparation method is particularly important for the mass production of SAPd (second generation) for which the catalytic activity was examined in ligand-free Buchwald-Hartwig cross-coupling reactions. The catalytic activities were the same between the first and second generation SAPds in aromatic aminations, but the lower palladium leaching properties and safer preparative method of second generation SAPd are a significant improvement over the first generation SAPd.

N-Heterocyclic carbene-catalyzed direct cross-aza-benzoin reaction: Efficient synthesis of α-amino-β-keto esters.

PubMed

Uno, Takuya; Kobayashi, Yusuke; Takemoto, Yoshiji

2012-01-01

An efficient catalytic synthesis of α-amino-β-keto esters has been newly developed. Cross-coupling of various aldehydes with α-imino ester, catalyzed by N-heterocyclic carbene, leads chemoselectively to α-amino-β-keto esters in moderate to good yields with high atom efficiency. The reaction mechanism is discussed, and it is proposed that the α-amino-β-keto esters are formed under thermodynamic control.

Interactions of soil-derived dissolved organic matter with phenol in peroxidase-catalyzed oxidative coupling reactions.

PubMed

Huang, Qingguo; Weber, Walter J

2004-01-01

The influence of dissolved soil organic matter (DSOM) derived from three geosorbents of different chemical composition and diagenetic history on the horseradish peroxidase (HRP) catalyzed oxidative coupling reactions of phenol was investigated. Phenol conversion and precipitate-product formation were measured, respectively, by HPLC and radiolabeled species analysis. Fourier transform infrared (FTIR) spectroscopy and capillary electrophoresis (CE) were used to characterize the products of enzymatic coupling, and the acute toxicities of the soluble products were determined by Microtox assay. Phenol conversion and precipitate formation were both significantly influenced by cross-coupling of phenol with dissolved organic matter, particularly in the cases of the more reactive and soluble DSOMs derived from two diagenetically "young" humic-type geosorbents. FTIR and CE characterizations indicate that enzymatic cross-coupling in these two cases leads to incorporation of phenol in DSOM macromolecules, yielding nontoxic soluble products. Conversely, cross-coupling appears to proceed in parallel with self-coupling in the presence of the relatively inert and more hydrophobic DSOM derived from a diagenetically "old" kerogen-type shale material. The products formed in this system have lower solubility and precipitate more readily, although their soluble forms tend to be more toxic than those formed by dominant cross-coupling reactions in the humic-type DSOM solutions. Several of the findings reported may be critically important with respect to feasibility evaluations and the engineering design of associated remediation schemes.

O2-Promoted Allylic Acetoxylation of Alkenes: Assessment of "Push" vs. "Pull" Mechanisms and Comparison between O2 and Benzoquinone.

PubMed

Diao, Tianning; Stahl, Shannon S

2014-12-14

Palladium-catalyzed acetoxylation of allylic C-H bonds has been the subject of extensive study. These reactions proceed via allyl-palladium(II) intermediates that react with acetate to afford the allyl acetate product. Benzoquinone and molecular oxygen are two common oxidants for these reactions. Benzoquinone has been shown to promote allyl acetate formation from well-defined π-allyl palladium(II) complexes. Here, we assess the ability of O 2 to promote similar reactions with a series of "unligated" π-allyl palladium(II) complexes (i.e., in the absence of ancillary phosphorus, nitrogen or related donor ligands). Stoichiometric and catalytic allyl acetate formation is observed under aerobic conditions with several different alkenes. Mechanistic studies are most consistent with a "pull" mechanism in which O 2 traps the Pd 0 intermediate following reversible C-O bond-formation from an allyl-palladium(II) species. A "push" mechanism, involving oxidatively induced C-O bond formation, does not appear to participate. These results and conclusions are compared with benzoquinone-promoted allylic acetoxylation, in which a "push" mechanism seems to be operative.

Synthesis of 2‐Alkynoates by Palladium(II)‐Catalyzed Oxidative Carbonylation of Terminal Alkynes and Alcohols

PubMed Central

Cao, Qun; Hughes, N. Louise

2016-01-01

Abstract A homogeneous PdII catalyst, utilizing a simple and inexpensive amine ligand (TMEDA), allows 2‐alkynoates to be prepared in high yields by an oxidative carbonylation of terminal alkynes and alcohols. The catalyst system overcomes many of the limitations of previous palladium carbonylation catalysts. It has an increased substrate scope, avoids large excesses of alcohol substrate and uses a desirable solvent. The catalyst employs oxygen as the terminal oxidant and can be operated under safer gas mixtures. PMID:27305489

Palladium(II)-Catalyzed Annulation between ortho-Alkenylphenols and Allenes. Key Role of the Metal Geometry in Determining the Reaction Outcome.

PubMed

Casanova, Noelia; Del Rio, Karina P; García-Fandiño, Rebeca; Mascareñas, José L; Gulías, Moisés

2016-05-06

2-Alkenylphenols react with allenes, upon treatment with catalytic amounts of Pd(II) and Cu(II), to give benzoxepine products in high yields and with very good regio- and diastereoselectivities. This contrasts with the results obtained with Rh catalysts, which provided chromene-like products through a pathway involving a β-hydrogen elimination step. Computational studies suggest that the square planar geometry of the palladium is critical to favor the reductive elimination process required for the formation of the oxepine products.

Challenging nickel-catalysed amine arylations enabled by tailored ancillary ligand design

PubMed Central

Lavoie, Christopher M.; MacQueen, Preston M.; Rotta-Loria, Nicolas L.; Sawatzky, Ryan S.; Borzenko, Andrey; Chisholm, Alicia J.; Hargreaves, Breanna K. V.; McDonald, Robert; Ferguson, Michael J.; Stradiotto, Mark

2016-01-01

Palladium-catalysed C(sp2)–N cross-coupling (that is, Buchwald–Hartwig amination) is employed widely in synthetic chemistry, including in the pharmaceutical industry, for the synthesis of (hetero)aniline derivatives. However, the cost and relative scarcity of palladium provides motivation for the development of alternative, more Earth-abundant catalysts for such transformations. Here we disclose an operationally simple and air-stable ligand/nickel(II) pre-catalyst that accommodates the broadest combination of C(sp2)–N coupling partners reported to date for any single nickel catalyst, without the need for a precious-metal co-catalyst. Key to the unprecedented performance of this pre-catalyst is the application of the new, sterically demanding yet electron-poor bisphosphine PAd-DalPhos. Featured are the first reports of nickel-catalysed room temperature reactions involving challenging primary alkylamine and ammonia reaction partners employing an unprecedented scope of electrophiles, including transformations involving sought-after (hetero)aryl mesylates for which no capable catalyst system is known. PMID:27004442

Formation of vinyl halides via a ruthenium-catalyzed three-component coupling.

PubMed

Trost, Barry M; Pinkerton, Anthony B

2002-06-26

The ruthenium-catalyzed three-component coupling of an alkyne, an enone, and halide ion to form E- or Z-vinyl halides has been investigated. Through systematic optimization experiments, the conditions effecting the olefin selectivity were examined. In general, more polar solvents such as DMF favored the formation of the E-isomer, and less polar solvents such as acetone favored formation of the Z-isomer. The optimized conditions for the formation of E-vinyl chlorides were found to be the use of cyclopentadienyl ruthenium (II) cyclooctadiene chloride, stannic chloride pentahydrate as a cocatalyst, and for a chloride source, either ammonium chloride in DMF/water mixtures or tetramethylammonium chloride in DMF. A range of several other ruthenium (II) catalysts was also shown to be effective. A wide variety of vinyl chlorides could be formed under these conditions. Substrates with tethered alcohols or ketones either five or six carbons from the alkyne portion gave instead diketone or cyclohexenone products. For formation of vinyl bromides, a catalyst system involving the use of cyclopentadienylruthenium (II) tris(acetonitrile) hexafluorophosphate with stannic bromide as a cocatalyst was found to be most effective. The use of ammonium bromide in DMF/acetone mixtures was optimal for the synthesis of E-vinyl bromides, and the use of lithium bromide in acetone was optimal for formation of the corresponding Z-isomer. Under either set of conditions, a wide range of vinyl bromides could be formed. When alkynes with propargylic substituents are used, enhanced selectivity for formation of the Z-isomer is observed. When aryl acetylenes are used as the coupling partners, complete selectivity for the Z-isomer is obtained. A mechanism involving a cis or trans halometalation is invoked to explain formation of the observed products. The vinyl halides have been shown to be precursors to alpha-hydroxy ketones and cyclopentenones, and as coupling partners in Suzuki-type reactions.

Architecture engineering toward highly active palladium integrated titanium dioxide yolk-double-shell nanoreactor for catalytic applications

NASA Astrophysics Data System (ADS)

Liu, Baocang; Wang, Qin; Yu, Shengli; Jing, Peng; Liu, Lixia; Xu, Guangran; Zhang, Jun

2014-09-01

Rational design of the hierarchical architecture of a material with well controlled functionality is crucially important for improving its properties. In this paper, we present the general strategies for rationally designing and constructing three types of hierarchical Pd integrated TiO2 double-shell architectures, i.e. yolk-double-shell TiO2 architecture (Pd@TiO2/Pd@TiO2) with yolk-type Pd nanoparticles residing inside the central cavity of the hollow TiO2 structure; ultrafine Pd nanoparticles homogenously dispersed on both the external and internal surfaces of the inner TiO2 shell; and double-shell TiO2 architecture (@TiO2/Pd@TiO2) with Pd nanoparticles solely loaded on the external surface of the inner TiO2 shell, and double-shell TiO2 architecture (@TiO2@Pd@TiO2) with Pd nanoparticles dispersed in the interlayer space of double TiO2 shells, via newly developed Pd2+ ion-diffusion and Pd sol impregnation methodologies. These architectures are well controlled in structure, size, morphology, and configuration with Pd nanoparticles existing in various locations. Owing to the variable synergistic effects arising from the location discrepancies of Pd nanoparticle in the architectures, they exhibit remarkable variations in catalytic activity. In particular, different from previously reported yolk-shell structures, the obtained yolk-double-shell Pd@TiO2/Pd@TiO2 architecture, which is revealed for the first time, possesses a uniform hierarchical structure, narrow size distribution, and good monodispersibility, and it creates two Pd-TiO2 interfaces on the external and internal surfaces of the inner TiO2 shell, leading to the strongest synergistic effect of Pd nanoparticles with TiO2 shell. Furthermore, the interlayer chamber between the double TiO2 shells connecting with the central cavity of the hollow TiO2 structure through the mesoporous TiO2 wall forms a nanoreactor for enriching the reactants and preventing the deletion of Pd nanoparticles during the reaction, thus greatly accelerating the reaction speed. Owing to its structural features, yolk-double-shell Pd@TiO2/Pd@TiO2 architecture exhibits extremely high catalytic performance on the Suzuki-Miyaura coupling reaction. The synthetic methodologies are robust for fabricating double-shell architectures with various configurations for applications such as in catalysis, drug delivery, and medicine release. The obtained double-shell architectures may be used as novel catalyst systems with highly efficient catalytic performance for other catalytic reactions.Rational design of the hierarchical architecture of a material with well controlled functionality is crucially important for improving its properties. In this paper, we present the general strategies for rationally designing and constructing three types of hierarchical Pd integrated TiO2 double-shell architectures, i.e. yolk-double-shell TiO2 architecture (Pd@TiO2/Pd@TiO2) with yolk-type Pd nanoparticles residing inside the central cavity of the hollow TiO2 structure; ultrafine Pd nanoparticles homogenously dispersed on both the external and internal surfaces of the inner TiO2 shell; and double-shell TiO2 architecture (@TiO2/Pd@TiO2) with Pd nanoparticles solely loaded on the external surface of the inner TiO2 shell, and double-shell TiO2 architecture (@TiO2@Pd@TiO2) with Pd nanoparticles dispersed in the interlayer space of double TiO2 shells, via newly developed Pd2+ ion-diffusion and Pd sol impregnation methodologies. These architectures are well controlled in structure, size, morphology, and configuration with Pd nanoparticles existing in various locations. Owing to the variable synergistic effects arising from the location discrepancies of Pd nanoparticle in the architectures, they exhibit remarkable variations in catalytic activity. In particular, different from previously reported yolk-shell structures, the obtained yolk-double-shell Pd@TiO2/Pd@TiO2 architecture, which is revealed for the first time, possesses a uniform hierarchical structure, narrow size distribution, and good monodispersibility, and it creates two Pd-TiO2 interfaces on the external and internal surfaces of the inner TiO2 shell, leading to the strongest synergistic effect of Pd nanoparticles with TiO2 shell. Furthermore, the interlayer chamber between the double TiO2 shells connecting with the central cavity of the hollow TiO2 structure through the mesoporous TiO2 wall forms a nanoreactor for enriching the reactants and preventing the deletion of Pd nanoparticles during the reaction, thus greatly accelerating the reaction speed. Owing to its structural features, yolk-double-shell Pd@TiO2/Pd@TiO2 architecture exhibits extremely high catalytic performance on the Suzuki-Miyaura coupling reaction. The synthetic methodologies are robust for fabricating double-shell architectures with various configurations for applications such as in catalysis, drug delivery, and medicine release. The obtained double-shell architectures may be used as novel catalyst systems with highly efficient catalytic performance for other catalytic reactions. Electronic supplementary information (ESI) available: Synthetic schemes, TEM, SEM, XRD, FTIR, UV-DRS spectra, TPR, and catalytic data. See DOI: 10.1039/c4nr02692f

Aerobic Asymmetric Dehydrogenative Cross-Coupling between Two C(sp3)-H Groups Catalyzed by a Chiral-at-Metal Rhodium Complex.

PubMed

Tan, Yuqi; Yuan, Wei; Gong, Lei; Meggers, Eric

2015-10-26

A sustainable C-C bond formation is merged with the catalytic asymmetric generation of one or two stereocenters. The introduced catalytic asymmetric cross-coupling of two C(sp3)-H groups with molecular oxygen as the oxidant profits from the oxidative robustness of a chiral-at-metal rhodium(III) catalyst and exploits an autoxidation mechanism or visible-light photosensitized oxidation. In the latter case, the catalyst serves a dual function, namely as a chiral Lewis acid for catalyzing enantioselective enolate chemistry and at the same time as a visible-light-driven photoredox catalyst. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Supramolecular self-assembly of heterobimetallic complexes: a new N,P-based, selective heteroditopic ligand.

PubMed

Hutchinson, Daniel John; Clauss, Reike; Sárosi, Menyhárt-Botond; Hey-Hawkins, Evamarie

2018-01-23

Pyrimidine-hydrazone and phosphole architectures have been combined to create a new heteroditopic ligand capable of forming heterobimetallic Zn II /Pd II , Pb II /Pd II and Cu II /Pd II complexes in high yielding stepwise or one pot reactions. The catalytic activity of these complexes in Heck coupling and Miyaura borylation reactions was investigated.

Quinolinone and pyridopyrimidinone inhibitors of DNA-dependent protein kinase.

PubMed

Barbeau, Olivier R; Cano-Soumillac, Celine; Griffin, Roger J; Hardcastle, Ian R; Smith, Graeme C M; Richardson, Caroline; Clegg, William; Harrington, Ross W; Golding, Bernard T

2007-08-21

8-Substituted 2-morpholin-4-yl-quinolin-4-ones and 9-substituted 2-morpholin-4-yl-pyrido[1,2-a]pyrimidin-4-ones with selected aryl and heteroaryl groups as the substituent have been synthesised as potential inhibitors of DNA-dependent protein kinase. A multiple-parallel approach, employing Suzuki cross-coupling methodology, was utilised in the preparation of 8-substituted 2-morpholin-4-yl-quinolin-4-ones. For this purpose 8-bromo-2-morpholin-4-yl-quinolin-4-one was required as an intermediate. This compound was obtained by adapting a literature route in which thermal cyclocondensation of (2-bromoanilino)-morpholin-4-yl-5-methylene-2,2-dimethyl[1,3]dioxane-4,6-dione afforded 8-bromo-2-morpholin-4-yl-quinolin-4-one. A multiple-parallel approach, employing Suzuki cross-coupling methodology, was also utilised to prepare 9-substituted 2-morpholin-4-yl-pyrido[1,2-a]pyrimidin-4-ones using 9-hydroxy-2-morpholin-4-yl-pyrido[1,2-a]pyrimidin-4-one O-trifluoromethanesulfonate as an intermediate. 8-Substituted 2-morpholin-4-yl-quinolin-4-ones and 9-substituted 2-morpholin-4-yl-pyrido[1,2-a]pyrimidin-4-ones were both inhibitors of DNA-dependent protein kinase. When the substituent was dibenzothiophen-4-yl, dibenzofuran-4-yl or biphen-3-yl, IC50 values in the low nanomolar range were observed. Interestingly, the pyridopyrimidinones and quinolinones were essentially equipotent with the corresponding 8-substituted 2-morpholin-4-yl-chromen-4-ones previously reported (I. R. Hardcastle, X. Cockcroft, N. J. Curtin, M. Desage El-Murr, J. J. J. Leahy, M. Stockley, B. T. Golding, L. Rigoreau, C. Richardson, G. C. M. Smith and R. J. Griffin, J. Med. Chem., 2005, 48, 7829-7846).

Rhodium-Catalyzed Boron Arylation of 1,2-Azaborines**

PubMed Central

Rudebusch, Gabriel E.; Zakharov, Lev N.; Liu, Shih-Yuan

2013-01-01

A Sn-phony in B! BN isosteres of biphenyl compounds are prepared through Rh-catalyzed cross-coupling between 2-chloro-1,2-azaborines and arylstannanes (see scheme). The synthetic method should enable investigations of structure–activity relationships (SARs) by expanding the chemical space of the pharmaceutically relevant biphenyl structure through BN/CC isosterism. PMID:23832871

Aerobic oxidation of alcohols in visible light on Pd-grafted Ti cluster

EPA Science Inventory

The titanium cluster with the reduced band gap has been synthesized having the palladium nanoparticles over the surface, which not only binds to the atmospheric oxygen but also catalyzes the oxidation of alcohols under visible light.

Dual palladium- and proline-catalyzed allylic alkylation of enolizable ketones and aldehydes with allylic alcohols.

PubMed

Usui, Ippei; Schmidt, Stefan; Breit, Bernhard

2009-03-19

The dual Pd/proline-catalyzed alpha-allylation reaction of a variety of enolizable ketones and aldehydes with allylic alcohols is described. In this reaction, the choice of a large-bite angle ligand Xantphos and proline as the organocatalyst was essential for generation of the crucial pi-allyl Pd intermediate from allylic alcohol, followed by nucleophilic attack of the enamine formed in situ from the corresponding enolizable carbonyl substrate and proline.

Multimetallic Catalysis Enabled Cross-Coupling of Aryl Bromides with Aryl Triflates

PubMed Central

Ackerman, Laura K.G.; Lovell, Matthew M.

2015-01-01

Transition metal-catalyzed strategies for the formation of new C-C bonds have revolutionized the field of organic chemistry, enabling the efficient synthesis of ligands, materials, and biologically active molecules.1–3 In cases where a single metal fails to promote a selective or efficient transformation, the synergistic cooperation4 of two distinct catalysts – multimetallic catalysis – can be employed instead. Many important reactions rely on multimetallic catalysis,5 including the Wacker oxidation of olefins6–8 and the Sonogashira coupling of alkynes with aryl halides.9–10 However, the application of this strategy, even in recently developed methods11, has largely been limited to the use of metals with distinct reactivities, with only one metal catalyst undergoing an oxidative addition.12 In this manuscript, we demonstrate that cooperativity between two d10 metal catalysts, (bipyridine)nickel and (1,3-bis(diphenylphosphino)propane)palladium, enables a general cross-Ullman reaction.13–15 Our method couples aryl bromides with aryl triflates directly, eliminating the use of arylmetal reagents and avoiding the challenge of differentiating between multiple C–H bonds that is required for many C–H activation methods.16–17 The selectivity does not require an excess of either substrate and originates from the orthogonal activity of the two catalysts and the relative stability of the two arylmetal intermediates. While (dppp)Pd reacts preferentially with aryl triflates to afford a persistent intermediate, (bpy)Ni reacts preferentially with aryl bromides to form a transient, reactive intermediate. Although each catalyst forms less than 5% cross product in isolation, together they are able to achieve up to 94% yield. Our results reveal a new, general method for the synthesis of biaryls, heteroaryls, and dienes, as well as a new mechanism for selective transmetalation between two catalysts. We anticipate that this reaction will simplify the synthesis of pharmaceutical agents, many of which are currently made with pre-formed organometallic reagents,1–3 and lead to the discovery of new multimetallic reactions. PMID:26280337

Z-Selective iridium-catalyzed cross-coupling of allylic carbonates and α-diazo esters.

PubMed

Thomas, Bryce N; Moon, Patrick J; Yin, Shengkang; Brown, Alex; Lundgren, Rylan J

2018-01-07

A well-defined Ir-allyl complex catalyzes the Z -selective cross-coupling of allyl carbonates with α-aryl diazo esters. The process overrides the large thermodynamic preference for E -products typically observed in metal-mediated coupling reactions to enable the synthesis of Z , E -dieneoates in good yield with selectivities consistently approaching or greater than 90 : 10. This transformation represents the first productive merger of Ir-carbene and Ir-allyl species, which are commonly encountered intermediates in allylation and cyclopropanation/E-H insertion catalysis. Potentially reactive functional groups (aryl halides, ketones, nitriles, olefins, amines) are tolerated owing to the mildness of reaction conditions. Kinetic analysis of the reaction suggests oxidative addition of the allyl carbonate to an Ir-species is rate-determining. Mechanistic studies uncovered a pathway for catalyst activation mediated by NEt 3 .

CuO nanoparticles catalyzed C-N, C-O, and C-S cross-coupling reactions: scope and mechanism.

PubMed

Jammi, Suribabu; Sakthivel, Sekarpandi; Rout, Laxmidhar; Mukherjee, Tathagata; Mandal, Santu; Mitra, Raja; Saha, Prasenjit; Punniyamurthy, Tharmalingam

2009-03-06

CuO nanoparticles have been studied for C-N, C-O, and C-S bond formations via cross-coupling reactions of nitrogen, oxygen, and sulfur nucleophiles with aryl halides. Amides, amines, imidazoles, phenols, alcohols and thiols undergo reactions with aryl iodides in the presence of a base such as KOH, Cs(2)CO(3), and K(2)CO(3) at moderate temperature. The procedure is simple, general, ligand-free, and efficient to afford the cross-coupled products in high yield.

2-Aryl-8-aza-3-deazaadenosine Analogues of 5’-O-[N-(Salicyl)sulfamoyl]adenosine: Nucleoside Antibiotics that Block Siderophore Biosynthesis in Mycobacterium tuberculosis

PubMed Central

Krajczyk, Anna; Zeidler, Joanna; Januszczyk, Piotr; Dawadi, Surendra; Boshoff, Helena I.; Barry, Clifton E.; Ostrowski, Tomasz; Aldrich, Courtney C.

2016-01-01

A series of 5’-O-[N-(salicyl)sulfamoyl]-2-aryl-8-aza-3-deazaadenosines were designed to block mycobactin biosynthesis in Mycobacterium tuberculosis (Mtb) through inhibition of the essential adenylating enzyme MbtA. The synthesis of the 2-aryl-8-aza-3-deazaadenosine nucleosides featured sequential copper-free palladium-catalyzed Sonogashira coupling of a precursor 4-cyano-5-iodo-1,2,3-triazolonucleoside with terminal alkynes and Minakawa-Matsuda annulation reaction. These modified nucleosides were shown to inhibit MbtA with apparent Ki values ranging from 6.1 to 25 nM and to inhibit Mtb growth under iron-deficient conditions with minimum inhibitory concentrations ranging from 12.5 to >50 μM. PMID:27265685

Synthesis and optical properties of new 5'-aryl-substituted 2,5-bis(3-decyl-2,2'-bithiophen-5-yl)-1,3,4-oxadiazoles.

PubMed

Kostyuchenko, Anastasia Sergeevna; Zheleznova, Tatyana Yu; Stasyuk, Anton Jaroslavovich; Kurowska, Aleksandra; Domagala, Wojciech; Pron, Adam; Fisyuk, Alexander S

2017-01-01

New photoluminescent donor-acceptor-donor (DAD) molecules, namely 5'-aryl-substituted 2,5-bis(3-decyl-2,2'-bithiophen-5-yl)-1,3,4-oxadiazoles were prepared by palladium-catalyzed coupling from readily available compounds such as ethyl 3-decyl-2,2'-bithiophene-5-carboxylate and aryl halides. The obtained compounds feature increasing bathochromic shifts in their emission spectra with increasing aryl-substituent size yielding blue to bluish-green emissions. At the same time, their absorption spectra are almost independent from the identity of the terminal substituent with λ max values ranging from 395 to 405 nm. The observed trends are perfectly predicted by quantum chemical DFT/TDDFT calculations carried out for these new molecules.

Synthesis and optical properties of new 5'-aryl-substituted 2,5-bis(3-decyl-2,2'-bithiophen-5-yl)-1,3,4-oxadiazoles

PubMed Central

Kostyuchenko, Anastasia Sergeevna; Zheleznova, Tatyana Yu; Stasyuk, Anton Jaroslavovich; Kurowska, Aleksandra; Domagala, Wojciech

2017-01-01

New photoluminescent donor–acceptor–donor (DAD) molecules, namely 5'-aryl-substituted 2,5-bis(3-decyl-2,2'-bithiophen-5-yl)-1,3,4-oxadiazoles were prepared by palladium-catalyzed coupling from readily available compounds such as ethyl 3-decyl-2,2'-bithiophene-5-carboxylate and aryl halides. The obtained compounds feature increasing bathochromic shifts in their emission spectra with increasing aryl-substituent size yielding blue to bluish-green emissions. At the same time, their absorption spectra are almost independent from the identity of the terminal substituent with λmax values ranging from 395 to 405 nm. The observed trends are perfectly predicted by quantum chemical DFT/TDDFT calculations carried out for these new molecules. PMID:28326140

Total synthesis of complestatin: development of a Pd(0)-mediated indole annulation for macrocyclization.

PubMed

Shimamura, Hiroyuki; Breazzano, Steven P; Garfunkle, Joie; Kimball, F Scott; Trzupek, John D; Boger, Dale L

2010-06-09

Full details of the initial development and continued examination of a powerful intramolecular palladium(0)-mediated indole annulation for macrocyclization closure of the strained 16-membered biaryl ring system found in complestatin (1, chloropeptin II) and the definition of factors impacting its intrinsic atropodiastereoselectivity are described. Its examination and use in an alternative, second-generation total synthesis of complestatin are detailed in which the order of the macrocyclization reactions was reversed from our first-generation total synthesis. In this approach and with the ABCD biaryl ether ring system in place, the key Larock cyclization was conducted with substrate 36 (containing four phenols, five secondary amides, one carbamate, and four labile aryl chlorides) and provided the product 37 (56%) exclusively as a single atropisomer (>20:1, detection limits) possessing the natural (R)-configuration. In this instance, the complexity of the substrate and the reverse macrocyclization order did not diminish the atropodiastereoselectivity; rather, it provided an improvement over the 4:1 selectivity that was observed with the analogous substrate used to provide the isolated DEF ring system in our first-generation approach. Just as significant, the atroposelectivity represents a complete reversal of the diasteroselectivity observed with analogous macrocyclizations conducted using a Suzuki biaryl coupling.

Synthesis and characterization of 6,6’-bis(2-hydroxyphenyl)-2,2’-bipyridine ligand and its interaction with ct-DNA

DOE Office of Scientific and Technical Information (OSTI.GOV)

Selamat, Norhidayah; Heng, Lee Yook; Hassan, Nurul Izzaty

2015-09-25

The tetradentate ligand with four donor atoms OONN was synthesized. Bis(phenoxy)bipyridine ligand was prepared by Suzuki coupling reaction between 6,6’-dibromo-2,2’-bipyridyl and 2-hydroxyphenylboronic acid with presence of palladium (II) acetate. Bis(phenoxy)bipyridine ligand was also synthesized by demethylating of 6,6’-bis(2-methoxyphenyl)-2,2’-bipyridyl ligand through solvent free reaction using pyridine hydrocloride. The formation of both phenoxy and methoxy ligands was confirmed by {sup 1}H, 2D cosy and {sup 13}C NMR spectroscopy, ESI-MS spectrometry, FTIR spectroscopy. The purity of the ligand was confirmed by melting point. Binding studies of small molecules with DNA are useful to understand the reaction mechanism and to provide guidance for themore » application and design of new and more efficient drugs targeted to DNA. In this study, the binding interaction between the synthesized ligand with calf thymus-DNA (ct-DNA) has been investigated by UV/Vis DNA titration study. From the UV/Vis DNA study, it shows that bis(phenoxy)bipyridine ligand bind with ct-DNA via outside binding with binding contant K{sub b} = 1.19 × 10{sup 3} ± 0.08 M{sup −1}.« less

Structure-Activity Relationships of Truncated C2- or C8-Substituted Adenosine Derivatives as Dual Acting A2A and A3 Adenosine Receptor Ligands

PubMed Central

Hou, Xiyan; Majik, Mahesh S.; Kim, Kyunglim; Pyee, Yuna; Lee, Yoonji; Alexander, Varughese; Chung, Hwa-Jin; Lee, Hyuk Woo; Chandra, Girish; Lee, Jin Hee; Park, Seul-gi; Choi, Won Jun; Kim, Hea Ok; Phan, Khai; Gao, Zhan-Guo; Jacobson, Kenneth A.; Choi, Sun; Lee, Sang Kook; Jeong, Lak Shin

2011-01-01

Truncated N6-substituted-4′-oxo- and 4′-thioadenosine derivatives with C2 or C8 substitution were studied as dual acting A2A and A3 adenosine receptor (AR) ligands. The lithiation-mediated stannyl transfer and palladium-catalyzed cross coupling reactions were utilized for functionalization of the C2 position of 6-chloropurine nucleosides. An unsubstituted 6-amino group and a hydrophobic C2 substituent were required for high affinity at the hA2AAR, but hydrophobic C8 substitution abolished binding at the hA2AAR. However, most of synthesized compounds displayed medium to high binding affinity at the hA3AR, regardless of C2 or C8 substitution, and low efficacy in a functional cAMP assay. Several compounds tended to be full hA2AAR agonists. C2 substitution probed geometrically through hA2AAR-docking, was important for binding in order of hexynyl > hexenyl > hexanyl. Compound 4g was the most potent ligand acting dually as hA2AAR agonist and hA3AR antagonist, which might be useful for treatment of asthma or other inflammatory diseases. PMID:22142423

Structure-activity relationships of truncated C2- or C8-substituted adenosine derivatives as dual acting A₂A and A₃ adenosine receptor ligands.

PubMed

Hou, Xiyan; Majik, Mahesh S; Kim, Kyunglim; Pyee, Yuna; Lee, Yoonji; Alexander, Varughese; Chung, Hwa-Jin; Lee, Hyuk Woo; Chandra, Girish; Lee, Jin Hee; Park, Seul-Gi; Choi, Won Jun; Kim, Hea Ok; Phan, Khai; Gao, Zhan-Guo; Jacobson, Kenneth A; Choi, Sun; Lee, Sang Kook; Jeong, Lak Shin

2012-01-12

Truncated N(6)-substituted-4'-oxo- and 4'-thioadenosine derivatives with C2 or C8 substitution were studied as dual acting A(2A) and A(3) adenosine receptor (AR) ligands. The lithiation-mediated stannyl transfer and palladium-catalyzed cross-coupling reactions were utilized for functionalization of the C2 position of 6-chloropurine nucleosides. An unsubstituted 6-amino group and a hydrophobic C2 substituent were required for high affinity at the hA(2A)AR, but hydrophobic C8 substitution abolished binding at the hA(2A)AR. However, most of synthesized compounds displayed medium to high binding affinity at the hA(3)AR, regardless of C2 or C8 substitution, and low efficacy in a functional cAMP assay. Several compounds tended to be full hA(2A)AR agonists. C2 substitution probed geometrically through hA(2A)AR docking was important for binding in order of hexynyl > hexenyl > hexanyl. Compound 4g was the most potent ligand acting dually as hA(2A)AR agonist and hA(3)AR antagonist, which might be useful for treatment of asthma or other inflammatory diseases.

Synthesis and SARs of novel lincomycin derivatives Part 5: optimization of lincomycin analogs exhibiting potent antibacterial activities by chemical modification at the 6- and 7-positions.

PubMed

Wakiyama, Yoshinari; Kumura, Ko; Umemura, Eijiro; Masaki, Satomi; Ueda, Kazutaka; Sato, Yasuo; Hirai, Yoko; Hayashi, Yoshio; Ajito, Keiichi

2018-02-01

In order to modify lincomycin at the C-6 and C-7 positions, we prepared target molecules, which have substituted pipecolinic acid at the 6-amino group and a para-substituted phenylthio group at the C-7 position, in application of palladium-catalyzed cross-coupling as a key reaction. As the result of structure-activity relationship (SAR) studies at the 6-position, analogs possessing 4'-cis-(cyclopropylmethyl)piperidine showed significantly strong antibacterial activities against Streptococcus pneumoniae and Streptococcus pyogenes with an erm gene. On the basis of SAR, we further synthesized novel analogs possessing 4'-cis-(cyclopropylmethyl)piperidine by transformation of a C-7 substituent. Consequently, novel derivatives possessing a para-heteroaromatic-phenylthio group at the C-7 position exhibited significantly strong activities against S. pneumoniae and S. pyogenes with an erm gene even when compared with those of telithromycin. Finally, in vivo efficacy of selected two derivatives was evaluated in a rat pulmonary infection model with resistant S. pneumoniae with erm + mef genes. One of them exhibited strong and constant in vivo efficacy in this model, and both compounds showed strong in vivo efficacy against resistant S. pneumoniae with a mef gene.

SELECTIVE OXIDATION OF STYRENE TO ACETOPHENONE IN PRESENCE OF IONIC LIQUIDS

EPA Science Inventory

Palladium-catalyzed oxidation of styrene (Wacker reaction) in the presence of 1,3-dialkylimidazolium cation based ionic liquids is described. The effect of temperature, use of co-catalyst, and recyclability aspects for the generation of carbonyl compounds using environmentally de...

Palladium-Catalyzed Borylation of Primary Alkyl Bromides

PubMed Central

Joshi-Pangu, Amruta; Ma, Xinghua; Diane, Mohamed; Iqbal, Sidra; Kribs, Robert J.; Huang, Richard; Wang, Chao-Yuan

2012-01-01

A mild Pd-catalyzed process for the borylation of alkyl bromides has been developed using bis(pinacolato)diboron as a boron source. This process accommodates the use of a wide range of functional groups on the alkyl bromide substrate. Primary bromides react with complete selectivity in the presence of a secondary bromide. The generality of this approach is demonstrated by its extension to the use of alkyl iodides and alkyl tosylates, as well as borylation reactions employing bis(neopentyl glycolato)diboron as the boron source. PMID:22774861

Reactivity of bromoselenophenes in palladium-catalyzed direct arylations.

PubMed

Skhiri, Aymen; Ben Salem, Ridha; Soulé, Jean-François; Doucet, Henri

2017-01-01

The reactivity of 2-bromo- and 2,5-dibromoselenophenes in Pd-catalyzed direct heteroarylation was investigated. From 2-bromoselenophene, only the most reactive heteroarenes could be employed to prepare 2-heteroarylated selenophenes; whereas, 2,5-dibromoselenophene generally gave 2,5-di(heteroarylated) selenophenes in high yields using both thiazole and thiophene derivatives. Moreover, sequential catalytic C2 heteroarylation, bromination, catalytic C5 arylation reactions allowed the synthesis of unsymmetrical 2,5-di(hetero)arylated selenophene derivatives in three steps from selenophene.

Introducing the New Class of N-Phosphoryl Ynamides via Cu(I)-Catalyzed Amidations of Alkynyl Bromides

PubMed Central

Walton, Mary C.; North, Troy D.

2011-01-01

We describe here the first synthesis of N-phosphoryl ynamides featuring C- and P-chirality via copper(I)-catalyzed amidative cross-couplings between phosphoramidates and phosphordiamidates with alkynyl bromides. Also featured is a tandem aza-Claisen–hetero-[2+2] cycloaddition for the synthesis of N-phosphoryl azetidin-2-imines. PMID:21848304

α-Oxo-Ketenimines from Isocyanides and α-Haloketones: Synthesis and Divergent Reactivity.

PubMed

Mamboury, Mathias; Wang, Qian; Zhu, Jieping

2017-09-18

The palladium-catalyzed reaction of α-haloketones with isocyanides afforded α-oxo-ketenimines through β-hydride elimination of the β-oxo-imidoyl palladium intermediates. Reaction of these relatively stable α-oxo-ketenimines with nucleophiles such as hydrazines, hydrazoic acid, amines, and Grignard reagent afforded pyrazoles, tetrazole, β-keto amidines, and enaminone, respectively, with high chemoselectivity. Whereas amines attack exclusively on the ketenimine functions, the formal [3+2] cycloaddition between N-monosubstituted hydrazines and α-oxo-ketenimines was initiated by nucleophilic addition to the carbonyl group. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Discovery, SAR, and X-ray Binding Mode Study of BCATm Inhibitors from a Novel DNA-Encoded Library

PubMed Central

2015-01-01

As a potential target for obesity, human BCATm was screened against more than 14 billion DNA encoded compounds of distinct scaffolds followed by off-DNA synthesis and activity confirmation. As a consequence, several series of BCATm inhibitors were discovered. One representative compound (R)-3-((1-(5-bromothiophene-2-carbonyl)pyrrolidin-3-yl)oxy)-N-methyl-2′-(methylsulfonamido)-[1,1′-biphenyl]-4-carboxamide (15e) from a novel compound library synthesized via on-DNA Suzuki–Miyaura cross-coupling showed BCATm inhibitory activity with IC50 = 2.0 μM. A protein crystal structure of 15e revealed that it binds to BCATm within the catalytic site adjacent to the PLP cofactor. The identification of this novel inhibitor series plus the establishment of a BCATm protein structure provided a good starting point for future structure-based discovery of BCATm inhibitors. PMID:26288694

O2-Promoted Allylic Acetoxylation of Alkenes: Assessment of “Push” vs. “Pull” Mechanisms and Comparison between O2 and Benzoquinone

PubMed Central

Diao, Tianning

2014-01-01

Palladium-catalyzed acetoxylation of allylic C–H bonds has been the subject of extensive study. These reactions proceed via allyl-palladium(II) intermediates that react with acetate to afford the allyl acetate product. Benzoquinone and molecular oxygen are two common oxidants for these reactions. Benzoquinone has been shown to promote allyl acetate formation from well-defined π-allyl palladium(II) complexes. Here, we assess the ability of O2 to promote similar reactions with a series of “unligated” π-allyl palladium(II) complexes (i.e., in the absence of ancillary phosphorus, nitrogen or related donor ligands). Stoichiometric and catalytic allyl acetate formation is observed under aerobic conditions with several different alkenes. Mechanistic studies are most consistent with a “pull” mechanism in which O2 traps the Pd0 intermediate following reversible C–O bond-formation from an allyl-palladium(II) species. A “push” mechanism, involving oxidatively induced C–O bond formation, does not appear to participate. These results and conclusions are compared with benzoquinone-promoted allylic acetoxylation, in which a “push” mechanism seems to be operative. PMID:25435646

Total Synthesis of Adunctin B.

PubMed

Dethe, Dattatraya H; Dherange, Balu D

2018-03-16

Total synthesis of (±)-adunctin B, a natural product isolated from Piper aduncum (Piperaceae), has been achieved using two different strategies, in seven and three steps. The efficient approach features highly atom economical and diastereoselective Friedel-Crafts acylation, alkylation reaction and palladium catalyzed Wacker type oxidative cyclization.

Template-constrained macrocyclic peptides prepared from native, unprotected precursors

PubMed Central

Lawson, Kenneth V.; Rose, Tristan E.; Harran, Patrick G.

2013-01-01

Peptide–protein interactions are important mediators of cellular-signaling events. Consensus binding motifs (also known as short linear motifs) within these contacts underpin molecular recognition, yet have poor pharmacological properties as discrete species. Here, we present methods to transform intact peptides into stable, templated macrocycles. Two simple steps install the template. The key reaction is a palladium-catalyzed macrocyclization. The catalysis has broad scope and efficiently forms large rings by engaging native peptide functionality including phenols, imidazoles, amines, and carboxylic acids without the necessity of protecting groups. The tunable reactivity of the template gives the process special utility. Defined changes in reaction conditions markedly alter chemoselectivity. In all cases examined, cyclization occurs rapidly and in high yield at room temperature, regardless of peptide composition or chain length. We show that conformational restraints imparted by the template stabilize secondary structure and enhance proteolytic stability in vitro. Palladium-catalyzed internal cinnamylation is a strong complement to existing methods for peptide modification. PMID:24043790

Conjugated ladder polymers by a cyclopentannulation polymerization

DOE PAGES

Bheemireddy, Sambasiva R.; Hautzinger, Matthew P.; Li, Tao; ...

2017-04-03

Here, we report a nontraditional synthesis of cyclopentafused-polycyclic aromatic hydrocarbon embedded ladder polymers using a palladium catalyzed cyclopentannulation polymerization followed by a cyclodehydrogenation reaction. Donor–acceptor type polymers containing a cyclopenta[hi]aceanthrylene acceptor groups can be synthesized by a palladium catalyzed copolymerization between 9,10-dibromoanthracene and a variety of bis(arylethynyl)arenes to give polymers with molecular weights (Mn) of 9–22 kDa. The bis(arylethynyl)arenes were composed of benzene, thiophene, or thieno[3,2- b]thiophene moieties, which provided access to a series of four donor–acceptor copolymers. The polymers were subjected to cyclodehydrogenation with FeCl 3 to access rigid ladder type polymers with the conversion investigated by 13C NMRmore » of isotopically labeled polymers. As a result, the ladder polymers possess broad UV–Vis absorptions and narrow optical band gaps of 1.17–1.29 eV and are p-type semiconductors in organic field effect transistors.« less

Conjugated ladder polymers by a cyclopentannulation polymerization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bheemireddy, Sambasiva R.; Hautzinger, Matthew P.; Li, Tao

Here, we report a nontraditional synthesis of cyclopentafused-polycyclic aromatic hydrocarbon embedded ladder polymers using a palladium catalyzed cyclopentannulation polymerization followed by a cyclodehydrogenation reaction. Donor–acceptor type polymers containing a cyclopenta[hi]aceanthrylene acceptor groups can be synthesized by a palladium catalyzed copolymerization between 9,10-dibromoanthracene and a variety of bis(arylethynyl)arenes to give polymers with molecular weights (Mn) of 9–22 kDa. The bis(arylethynyl)arenes were composed of benzene, thiophene, or thieno[3,2- b]thiophene moieties, which provided access to a series of four donor–acceptor copolymers. The polymers were subjected to cyclodehydrogenation with FeCl 3 to access rigid ladder type polymers with the conversion investigated by 13C NMRmore » of isotopically labeled polymers. As a result, the ladder polymers possess broad UV–Vis absorptions and narrow optical band gaps of 1.17–1.29 eV and are p-type semiconductors in organic field effect transistors.« less

Synthesis and PET studies of [11C-cyano]letrozole (Femara®), an aromatase inhibitor drug

PubMed Central

Kil, Kun-Eek; Biegon, Anat; Ding, Yu-Shin; Fischer, Andre; Ferrieri, Richard A.; Kim, Sung Won; Pareto, Deborah; Schueller, Michael J.; Fowler, Joanna S.

2011-01-01

Introduction Aromatase, a member of the cytochrome P450 family, converts androgens such as androstenedione and testosterone to estrone and estradiol respectively. Letrozole (1-[bis-(4-cyanophenyl)methyl]-1H-1,2,4-triazole, Femara®) is a high affinity aromatase inhibitor (Ki=11.5 nM) which has FDA approval for breast cancer treatment. Here we report the synthesis of carbon-11 labeled letrozole and its assessment as a radiotracer for brain aromatase in the baboon. Methods Letrozole and its precursor (4-[(4-bromophenyl)-1H-1,2,4-triazol-1-ylmethyl]benzonitrile, 3) were prepared in two-step syntheses from 4-cyanobenzyl bromide and 4-bromobenzyl bromide, respectively. The [11C]cyano group was introduced via the tetrakis(triphenylphosphine)palladium(0) catalyzed coupling of [11C]cyanide with the bromo-precursor (3). PET studies in the baboon brain were carried out to assess regional distribution and kinetics, reproducibility of repeated measures and saturability. The free fraction of letrozole in the plasma, log D, and the [11C-cyano]letrozole fraction in the arterial plasma were also measured. Results [11C-cyano]Letrozole was synthesized in 60 min with a radiochemical yield of 79–80%, with a radiochemical purity greater than 98% and a specific activity of 4.16±2.21 Ci/μmol at the end of bombardment (n=4). PET studies in the baboon revealed initial rapid and high uptake and initial rapid clearance followed by slow clearance of carbon-11 from the brain with no difference between brain regions. The brain kinetics was not affected by co-injection of unlabeled letrozole (0.1 mg/kg). The free fraction of letrozole in plasma was 48.9% and log D was 1.84. Conclusion [11C-cyano]Letrozole is readily synthesized via a palladium catalyzed coupling reaction with [11C]cyanide. Although it is unsuitable as a PET radiotracer for brain aromatase as revealed by the absence of regional specificity and saturability in brain regions, such as amygdala, which are known to contain aromatase, it may be useful in measuring letrozole distribution and pharmacokinetics in brain and peripheral organs. PMID:19217534

Synthesis and PET studies of [(11)C-cyano]letrozole (Femara), an aromatase inhibitor drug.

PubMed

Kil, Kun-Eek; Biegon, Anat; Ding, Yu-Shin; Fischer, Andre; Ferrieri, Richard A; Kim, Sung Won; Pareto, Deborah; Schueller, Michael J; Fowler, Joanna S

2009-02-01

Aromatase, a member of the cytochrome P450 family, converts androgens such as androstenedione and testosterone into estrone and estradiol, respectively. Letrozole (1-[bis-(4-cyanophenyl)methyl]-1H-1,2,4-triazole; Femara) is a high-affinity aromatase inhibitor (K(i)=11.5 nM) that has Food and Drug Administration approval for breast cancer treatment. Here we report the synthesis of carbon-11-labeled letrozole and its assessment as a radiotracer for brain aromatase in the baboon. Letrozole and its precursor (4-[(4-bromophenyl)-1H-1,2,4-triazol-1-ylmethyl]benzonitrile) were prepared in a two-step synthesis from 4-cyanobenzyl bromide and 4-bromobenzyl bromide, respectively. The [(11)C]cyano group was introduced via tetrakis(triphenylphosphine)palladium(0)-catalyzed coupling of [(11)C]cyanide with the bromo precursor. Positron emission tomography (PET) studies in the baboon brain were carried out to assess regional distribution and kinetics, reproducibility of repeated measures and saturability. Log D, the free fraction of letrozole in plasma and the [(11)C-cyano]letrozole fraction in arterial plasma were also measured. [(11)C-cyano]Letrozole was synthesized in 60 min with a radiochemical yield of 79-80%, with a radiochemical purity greater than 98% and a specific activity of 4.16+/-2.21 Ci/mumol at the end of bombardment (n=4). PET studies in the baboon revealed initial rapid and high uptake and initial rapid clearance, followed by slow clearance of carbon-11 from the brain, with no difference between brain regions. Brain kinetics was not affected by coinjection of unlabeled letrozole (0.1 mg/kg). The free fraction of letrozole in plasma was 48.9%, and log D was 1.84. [(11)C-cyano]Letrozole is readily synthesized via a palladium-catalyzed coupling reaction with [(11)C]cyanide. Although it is unsuitable as a PET radiotracer for brain aromatase, as revealed by the absence of regional specificity and saturability in brain regions such as amygdala, which are known to contain aromatase, it may be useful in measuring letrozole distribution and pharmacokinetics in the brain and peripheral organs.

DOE Office of Scientific and Technical Information (OSTI.GOV)

kil K. E.; Biegon A.; Kil, K.-E.

Aromatase, a member of the cytochrome P450 family, converts androgens such as androstenedione and testosterone to estrone and estradiol respectively. Letrozole (1-[bis-(4-cyanophenyl)methyl]-1H-1,2,4-triazole, Femara{reg_sign}) is a high affinity aromatase inhibitor (K{sub i}=11.5 nM) which has FDA approval for breast cancer treatment. Here we report the synthesis of carbon-11 labeled letrozole and its assessment as a radiotracer for brain aromatase in the baboon. Letrozole and its precursor (4-[(4-bromophenyl)-1H-1,2,4-triazol-1-ylmethyl]benzonitrile, 3) were prepared in two-step syntheses from 4-cyanobenzyl bromide and 4-bromobenzyl bromide, respectively. The [{sup 11}C]cyano group was introduced via the tetrakis(triphenylphosphine)palladium(0) catalyzed coupling of [{sup 11}C]cyanide with the bromo-precursor (3). PET studies inmore » the baboon brain were carried out to assess regional distribution and kinetics, reproducibility of repeated measures and saturability. The free fraction of letrozole in the plasma, log D, and the [{sup 11}C-cyano]letrozole fraction in the arterial plasma were also measured. [{sup 11}C-cyano]Letrozole was synthesized in 60 min with a radiochemical yield of 79-80%, with a radiochemical purity greater than 98% and a specific activity of 4.16 {+-} 2.21 Ci/{micro}mol at the end of bombardment (n=4). PET studies in the baboon revealed initial rapid and high uptake and initial rapid clearance followed by slow clearance of carbon-11 from the brain with no difference between brain regions. The brain kinetics was not affected by co-injection of unlabeled letrozole (0.1 mg/kg). The free fraction of letrozole in plasma was 48.9% and log D was 1.84. [{sup 11}C-cyano]Letrozole is readily synthesized via a palladium catalyzed coupling reaction with [{sup 11}C]cyanide. Although it is unsuitable as a PET radiotracer for brain aromatase as revealed by the absence of regional specificity and saturability in brain regions, such as amygdala, which are known to contain aromatase, it may be useful in measuring letrozole distribution and pharmacokinetics in brain and peripheral organs.« less

Solvent-free cross-dehydrogenative coupling reactions under high speed ball-milling conditions applied to the synthesis of functionalized tetrahydroisoquinolines.

PubMed

Su, Weike; Yu, Jingbo; Li, Zhenhua; Jiang, Zhijiang

2011-11-04

Solvent-free reaction using a high-speed ball milling technique has been first applied to cross-dehydrogenative coupling (CDC) reactions between tetrahydroisoquinolines and three types of pronucleophiles such as nitroalkanes, alkynes, and indoles. All coupling products were obtained in good yields at short reaction times (no more than 40 min). When alkynes and indoles were used as pronucleophile, the reactions can be catalyzed efficiently by recoverable copper balls without any additional metal catalyst.

Remote C-H Activation of Quinolines through Copper-Catalyzed Radical Cross-Coupling.

PubMed

Xu, Jun; Shen, Chao; Zhu, Xiaolei; Zhang, Pengfei; Ajitha, Manjaly J; Huang, Kuo-Wei; An, Zhongfu; Liu, Xiaogang

2016-03-18

Achieving site selectivity in carbon-hydrogen (C-H) functionalization reactions is a formidable challenge in organic chemistry. Herein, we report a novel approach to activating remote C-H bonds at the C5 position of 8-aminoquinoline through copper-catalyzed sulfonylation under mild conditions. Our strategy shows high conversion efficiency, a broad substrate scope, and good toleration with different functional groups. Furthermore, our mechanistic investigations suggest that a single-electron-transfer process plays a vital role in generating sulfonyl radicals and subsequently initiating C-S cross-coupling. Importantly, our copper-catalyzed remote functionalization protocol can be expanded for the construction of a variety of chemical bonds, including C-O, C-Br, C-N, C-C, and C-I. These findings provide a fundamental insight into the activation of remote C-H bonds, while offering new possibilities for rational design of drug molecules and optoelectronic materials requiring specific modification of functional groups. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Silver-catalyzed double-decarboxylative cross-coupling of α-keto acids with cinnamic acids in water: a strategy for the preparation of chalcones.

PubMed

Zhang, Ning; Yang, Daoshan; Wei, Wei; Yuan, Li; Nie, Fafa; Tian, Laijin; Wang, Hua

2015-03-20

A silver-catalyzed double-decarboxylative protocol has been proposed for the construction of chalcone derivatives via cascade coupling of substituted α-keto acids with cinnamic acids under the mild aqueous conditions. The developed method for constructing C-C bonds via double-decarboxylative reactions is efficient, practical, and environmentally benign by using the readily available starting materials. It should provide a promising synthesis candidate for the formation of diverse and useful chalcone derivatives in the fields of synthetic and pharmaceutical chemistry.

Metallocenyl dendrimers and their applications in molecular electronics, sensing, and catalysis.

PubMed

Astruc, Didier; Ornelas, Cátia; Ruiz, Jaime

2008-07-01

We have investigated the movement of electrons around the peripheries of dendrimers and between their redox termini and electrodes through studies of the electrochemistry of dendrimers presenting metallocenes (and other transition metal sandwich complexes) as terminal groups. Because these compounds can be stabilized in both their oxidized and their reduced forms, their electrochemical and chemical redox processes proceed without decomposition (chemical reversibility). Most interestingly, electrochemical studies reveal that electron transfer within the dendrimers and between the dendrimers and electrodes are both very fast processes when the branches are flexible (electrochemical reversibility). When the dendrimer branches are sufficiently long, the redox events at the many termini of the metallodendrimer are independent, appearing as a single wave in the cyclic voltammogram, because of very weak electrostatic effects. As a result, these metallodendrimers have applications in the molecular recognition, sensing, and titration of anions (e.g., ATP(2-)) and cations (e.g., transition metal complexes). When the recognition properties are coupled with catalysis, the metallodendrimers function in an enzyme-like manner. For example, Pd(II) can be recognized and titrated using the dendrimer's terminal redox centers and internal coordinate ligands. Redox control over the number of Pd(II) species located within a dendrimer allows us to predetermine the number of metal atoms that end up in the form of a dendrimer-encapsulated Pd nanoparticle (PdNP). For hydrogenation of olefins, the efficiency (turnover frequency, TOF) and stability (turnover number, TON) depend on the size of the dendrimer-encapsulated PdNP catalysts, similar to the behavior of polymer-supported PdNP catalysts, suggesting a classic mechanism in which all of the steps proceed on the PdNP surface. On the other hand, Miyaura-Suzuki carbon-carbon bond-forming reactions catalyzed by dendrimer-encapsulated PdNPs proceed with TOFs and TONs that do not depend on the size of the PdNPs. Moreover these catalysts are more efficient when employed in lower (down to "homeopathic") amounts, presumably because of a leaching mechanism whereby Pd atoms escape from the PdNP surface subsequent to oxidative addition of the aryl halide. Under these conditions, the "mother" PdNPs have greater difficulty quenching the extremely active leached Pd atoms because of their low concentration. Although dendrimers presenting catalysts at their branch termini can be recovered and reused readily, their inner-sphere components can lead to steric inhibition of substrate approach. In contrast, star-shaped catalysts do not suffer from such steric problems, as has been demonstrated for water-soluble dendrimers bearing cationic iron-sandwich termini, which are redox catalysts of cathodic nitrate and nitrite reduction in water.

Mesoporous poly(ionic liquid) supported palladium(II) catalyst for oxidative coupling of benzene under atmospheric oxygen

NASA Astrophysics Data System (ADS)

Liu, Yangqing; Wang, Kai; Hou, Wei; Shan, Wanjian; Li, Jing; Zhou, Yu; Wang, Jun

2018-01-01

Multi-functional mesoporous poly(ionic liquid) (MPIL) containing pyridine-based ionic liquid (IL) moieties and adjacent double sbnd COOH groups was synthesized through the free radical copolymerization of IL monomer N-propane sulfonate-4-vinylpyridine, maleic anhydride and divinylbenzene. Palladium(II) species were anchored on this MPIL support, affording the first efficient heterogeneous catalyst for the oxidative coupling of benzene to biphenyl under atmospheric oxygen at low temperature. The biphenyl yield of 15.0% (selectivity: 98.5%, turnover number: 62) was even higher than the one over the homogeneous counterpart palladium acetate. The catalyst can be facilely separated and reused. The IL moiety in the polymeric framework endowed the formation of immobilized palladium(II) species with high electrophilicity, which responds to the high performance.

Nanoparticle-supported and magnetically recoverable palladium (Pd) catalyst: a selective and sustainable oxidation protocol with high turnover number

EPA Science Inventory

A magnetic nanoparticle-supported ruthenium hydroxide catalyst was readily prepared from inexpensive starting materials and shown to catalyze hydration of nitriles with excellent yield in benign aqueous medium. Catalyst recovery using an external magnetic field, superior activity...

DOE Office of Scientific and Technical Information (OSTI.GOV)

Aubart, M.A.; Chandler, B.D.; Gould, R.A.T.

Platinum- and palladium-gold cluster compounds were evaluated with respect to their ability to catalyze H{sub 2}-D{sub 2} equilibration. In addition, these phosphine-stabilized complexes were structurally characterized. Mechanistic studies for this reaction were performed by kinetic and spectroscopic analysis. The catalytic reaction appears to occur in three steps, which were determined.

Heterobimetallic Pd-Sn catalysis: a Suzuki, tandem ring-closing sequence toward indeno[2,1-b]thiophenes and indeno[2,1-b]indoles.

PubMed

Das, Debjit; Pratihar, Sanjay; Roy, Sujit

2012-09-21

Indeno[2,1-b]thiophene and indeno[1,2-b]indole motifs have been obtained in moderate to good yields from easily available substituted boronic acids, 2-bromo aryl/vinyl aldehydes, and nucleophiles such as arenes/heteroarenes and others using a catalytic combination of bimetallic "Pd-Sn" and AgPF(6). This formal three-component coupling involves a Suzuki reaction followed by nucleophile assisted tandem ring closure. The sequential synthesis of substituted heterocycle-fused indenes, benzofluorene, and fluorenes was also accomplished.

Copper-catalyzed cross-coupling reactions of epoxides with gem-diborylmethane: access to γ-hydroxyl boronic esters.

PubMed

Ebrahim-Alkhalil, Ahmed; Zhang, Zhen-Qi; Gong, Tian-Jun; Su, Wei; Lu, Xiao-Yu; Xiao, Bin; Fu, Yao

2016-04-07

Herein, we describe a novel copper-catalyzed epoxide opening reaction with gem-diborylmethane. Aliphatic, aromatic epoxides as well as aziridines are converted to the corresponding γ-pinacolboronate alcohols or amines in moderate to excellent yields. This new reaction provides beneficial applications for classic epoxide substrates as well as interesting gem-diborylalkane reagents.

Catalytic Properties of Unsupported Palladium Nanoparticle Surfaces Capped with Small Organic Ligands

PubMed Central

Gavia, Diego J.

2015-01-01

This Minireview summarizes a variety of intriguing catalytic studies accomplished by employing unsupported, either solubilized or freely mobilized, and small organic ligand-capped palladium nanoparticles as catalysts. Small organic ligands are gaining more attention as nanoparticle stabilizers and alternates to larger organic supports, such as polymers and dendrimers, owing to their tremendous potential for a well-defined system with spatial control in surrounding environments of reactive surfaces. The nanoparticle catalysts are grouped depending on the type of surface stabilizers with reactive head groups, which include thiolate, phosphine, amine, and alkyl azide. Applications for the reactions such as hydrogenation, alkene isomerization, oxidation, and carbon-carbon cross coupling reactions are extensively discussed. The systems defined as “ligandless” Pd nanoparticle catalysts and solvent (e.g. ionic liquid)-stabilized Pd nanoparticle catalysts are not discussed in this review. PMID:25937846

Room-temperature enantioselective C-H iodination via kinetic resolution.

PubMed

Chu, Ling; Xiao, Kai-Jiong; Yu, Jin-Quan

2014-10-24

Asymmetric carbon-hydrogen (C-H) activation reactions often rely on desymmetrization of prochiral C-H bonds on the same achiral molecule, using a chiral catalyst. Here, we report a kinetic resolution via palladium-catalyzed enantioselective C-H iodination in which one of the enantiomers of a racemic benzylic amine substrates undergoes faster aryl C-H insertion with the chiral catalysts than the other. The resulting enantioenriched C-H functionalization products would not be accessible through desymmetrization of prochiral C-H bonds. The exceedingly high relative rate ratio (k(fast)/k(slow) up to 244), coupled with the subsequent iodination of the remaining enantiomerically enriched starting material using a chiral ligand with the opposite configuration, enables conversion of both substrate enantiomers into enantiomerically pure iodinated products. Copyright © 2014, American Association for the Advancement of Science.

Pd-N-Heterocyclic Carbene (NHC) Organic Silica: Synthesis and Application in Carbon-Carbon Coupling Reactions

EPA Science Inventory

The first Pd-N-heterocyclic carbene (NHC) complex in the form of organic silica was prepared using sol-gel method and its application in Heck and Suzuki reaction were demonstrated. These C-C coupling reactions proceeded efficiently under the influence of microwave irradiation, wi...

α,α'-N-Boc-substituted bi- and terthiophenes: fluorescent precursors for functional materials.

PubMed

Dong, Yanmei; Navarathne, Daminda; Bolduc, Andréanne; McGregor, Nicholas; Skene, W G

2012-06-15

Fluorescent α,α'-diamide substituted bi- and terthiophene derivatives were prepared by Stille and Suzuki couplings. Their one-pot deprotection and coupling with 2-thiophene carboxaldehyde led to stable conjugated azomethines. These exhibited electrochromic properties, and they were used to fabricate a working electrochromic device.

Ambient ammonia synthesis via palladium-catalyzed electrohydrogenation of dinitrogen at low overpotential.

PubMed

Wang, Jun; Yu, Liang; Hu, Lin; Chen, Gang; Xin, Hongliang; Feng, Xiaofeng

2018-05-15

Electrochemical reduction of N 2 to NH 3 provides an alternative to the Haber-Bosch process for sustainable, distributed production of NH 3 when powered by renewable electricity. However, the development of such process has been impeded by the lack of efficient electrocatalysts for N 2 reduction. Here we report efficient electroreduction of N 2 to NH 3 on palladium nanoparticles in phosphate buffer solution under ambient conditions, which exhibits high activity and selectivity with an NH 3 yield rate of ~4.5 μg mg -1 Pd h -1 and a Faradaic efficiency of 8.2% at 0.1 V vs. the reversible hydrogen electrode (corresponding to a low overpotential of 56 mV), outperforming other catalysts including gold and platinum. Density functional theory calculations suggest that the unique activity of palladium originates from its balanced hydrogen evolution activity and the Grotthuss-like hydride transfer mechanism on α-palladium hydride that lowers the free energy barrier of N 2 hydrogenation to *N 2 H, the rate-limiting step for NH 3 electrosynthesis.

Selective Ether/Ester C–O Cleavage of an Acetylated Lignin Model via Tandem Catalysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lohr, Tracy L.; Li, Zhi; Marks, Tobin J.

2015-11-06

Lignin, a heterogeneous phenolic polymer which constitutes roughly 15 to 20 wt % of lignocellulosic biomass (cellulose, hemicellose, and lignin), represents one of the few renewable sources of aromatic monomers.(1) Current lignin depolymerization methodologies, including base-catalyzed,(2) acid-catalyzed,(3) metal-catalyzed,(4) ionic liquid (IL)-assisted,(5) and supercritical-fluid-assisted(2b, 6) approaches, typically afford low yields (~10–20% or less) of low molecular weight aromatics under relatively harsh reaction conditions (>300 °C).(7) Recent advances include using oxidized lignin and lignin models,(8) where oxidation of the Cα alcohol facilitates depolymerizaton, with aromatic monomer yields reaching up to 52% for aspen “hardwood” lignin.(9) The most common structural lignin motifs containmore » a β-O-4 aryl-ether linkage,(10) a primary alcohol in the γ skeletal position, and a secondary alcohol in the α position (Scheme 1). Our laboratory has previously demonstrated an effective strategy for thermodynamically leveraged etheric and esteric C–O bond hydrogenolysis using a tandem metal triflate + supported palladium catalytic system.(11) A homogeneous M(OTf)n catalyst mediates endothermic ether or near thermoneutral ester C–O bond scission (the reverse of hydroelementation), which is coupled to exothermic Pd-catalyzed hydrogenation of the resulting C=C unsaturation, driving the overall process downhill. We next asked whether this tandem system might be applicable to cleaving the β-O-4 aryl-ether bond in lignin and lignin models. The promising results of that investigation are communicated here.« less

Aerobic oxidation of alcohols in visible light on Pd-grafted Ti ...

EPA Pesticide Factsheets

The titanium cluster with the reduced band gap has been synthesized having the palladium nanoparticles over the surface, which not only binds to the atmospheric oxygen but also catalyzes the oxidation of alcohols under visible light. Prepared as an invited article for submission to the Elsevier journal, Tetrahedron.

Divergent pathways in the reaction of Fischer carbenes and palladium.

PubMed

López-Alberca, María P; Mancheño, María J; Fernandez, Israel; Gómez-Gallego, Mar; Sierra, Miguel A; Torres, Rosario

2007-04-26

[reaction: see text] The Pd-catalyzed reaction of beta-arylaminochromium(0) carbene complexes produces by transmetalation the first isolated and X-ray structurally characterized bis-Pd(II) carbene complex, as well as other alternative reaction pathways, such as the oxidative addition-transmetalation sequence, not seen before in this chemistry.

Palladium-Mediated Catalysis Leads to Intramolecular Narcissistic Self-Sorting on a Cavitand Platform.

PubMed

Nagymihály, Zoltán; Caturello, Naidel A M S; Takátsy, Anikó; Aragay, Gemma; Kollár, László; Albuquerque, Rodrigo Q; Csók, Zsolt

2017-01-06

Palladium-catalyzed aminocarbonylation reactions have been used to directly convert a tetraiodocavitand intermediate into the corresponding carboxamides and 2-ketocarboxamides. When complex mixtures of the amine reactants are employed in competition experiments using polar solvents, such as DMF, no "mixed" products possessing structurally different amide fragments are detected either by 1 H or 13 C NMR. Only highly symmetrical cavitands are sorted out of a large number of potentially feasible products, which represents a rare example of intramolecular, narcissistic self-sorting. Our experimental results along with thermodynamic energy analysis suggest that the observed self-sorting is a symmetry-driven, kinetically controlled process.

Palladium-Catalyzed Carbon-Fluorine and Carbon-Hydrogen Bond Alumination of Fluoroarenes and Heteroarenes.

PubMed

Chen, Wenyi; Hooper, Thomas N; Ng, Jamues; White, Andrew J P; Crimmin, Mark R

2017-10-02

Through serendipitous discovery, a palladium bis(phosphine) complex was identified as a catalyst for the selective transformation of sp 2 C-F and sp 2 C-H bonds of fluoroarenes and heteroarenes to sp 2 C-Al bonds (19 examples, 1 mol % Pd loading). The carbon-fluorine bond functionalization reaction is highly selective for the formation of organoaluminium products in preference to hydrodefluorination products (selectivity=4.4:1 to 27:1). Evidence is presented for a tandem catalytic process in which hydrodefluorination is followed by sp 2 C-H alumination. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

New cross-coupling reaction of arylbromide with arylboric acid catalyzed by nano metals

NASA Astrophysics Data System (ADS)

An, Zhong W.; Chen, Xin B.

2002-06-01

Synthetic method of compounds 4,4'-bis-(trans-4- alkylcyclohexyl) biphenyl by cross-coupling reaction of arylboric acid and arylbromide in the presence of cetrimonium bromide over nano Ni or Cu catalyst is presented. The reaction is carried out under reflux temperature in THF/H2O for 15 h with yield 60% to approximately 65% for nano nickel and 25% to approximately 30% for nano copper.

Rh(I)-Catalyzed Intermolecular Hydroacylation: Enantioselective Cross-Coupling of Aldehydes and Ketoamides

PubMed Central

2015-01-01

Under Rh(I) catalysis, α-ketoamides undergo intermolecular hydroacylation with aliphatic aldehydes. A newly designed Josiphos ligand enables access to α-acyloxyamides with high atom-economy and enantioselectivity. On the basis of mechanistic and kinetic studies, we propose a pathway in which rhodium plays a dual role in activating the aldehyde for cross-coupling. A stereochemical model is provided to rationalize the sense of enantioinduction observed. PMID:24937681

Dehydrogenative coupling of silanes with alcohols catalyzed by Cu3(BTC)2.

PubMed

Dhakshinamoorthy, Amarajothi; Concepcion, Patricia; Garcia, Hermenegildo

2016-02-14

Cu3(BTC)2 is an efficient and reusable heterogeneous catalyst for the dehydrogenative coupling of silanes with alcohols. Activity data and CO adsorption suggest that Cu(II) and in situ generated Cu(I) are the active species. Other MOFs such as Fe(BTC), MIL-101(Cr) and UiO-66(Zr) are unable to promote this cross-coupling.

POLAR, NON-COORDINATING IONIC LIQUIDS AS SOLVENTS FOR ALTERNATING COPOLYMERIZATION OF STYRENE AND CO CATALYZED BY CATIONIC PALLADIUM CATALYSTS. (R828257)

EPA Science Inventory

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

Synthesis and properties of functionalized 4 nm scale molecular wires with thiolated termini for self-assembly onto metal surfaces.

PubMed

Wang, Changsheng; Bryce, Martin R; Gigon, Joanna; Ashwell, Geoffrey J; Grace, Iain; Lambert, Colin J

2008-07-04

We report the synthesis of new oligo(aryleneethynylene) molecular wires of ca. 4 nm length scale by palladium-catalyzed Sonogashira cross-coupling methodology. Key structural features are the presence of electron donor 9-(1,3-dithiol-2-ylidene)fluorene (compounds 13 and 14) and electron acceptor 9-[di(4-pyridyl)methylene]fluorene units (compound 16) at the core of the molecules. Terminal thiolate substituents are protected as cyanoethylsulfanyl (13 and 16) or thioacetate derivatives (14). The molecules display well-defined redox processes in solution electrochemical studies. The optical properties in solution are similar to those of the fluorenone analog 6: the strongest absorptions for 6, 13 and 16 are in the region lambda(max) = 387-393 nm, with 13 showing an additional shoulder at 415 nm which is not present for 6 and 16; this shoulder is assigned to a HOMO-LUMO transition from the dithiole to the fluorene unit. Molecules 6, 13, 14 and 16 form self-assembled monolayers on gold substrates which exhibit essentially symmetrical current-voltage (I-V) characteristics when contacted by a gold scanning tunelling microscope (STM) tip. The effects of the chemical modifications at the central unit of 6, 14 and 16 on the HOMO-LUMO levels and electron transport through the molecules in vacuum have been computed by an ab initio approach.

Microwave-assisted intramolecular dehydrogenative Diels-Alder reactions for the synthesis of functionalized naphthalenes/solvatochromic dyes.

PubMed

Kocsis, Laura S; Benedetti, Erica; Brummond, Kay M

2013-04-01

Functionalized naphthalenes have applications in a variety of research fields ranging from the synthesis of natural or biologically active molecules to the preparation of new organic dyes. Although numerous strategies have been reported to access naphthalene scaffolds, many procedures still present limitations in terms of incorporating functionality, which in turn narrows the range of available substrates. The development of versatile methods for direct access to substituted naphthalenes is therefore highly desirable. The Diels-Alder (DA) cycloaddition reaction is a powerful and attractive method for the formation of saturated and unsaturated ring systems from readily available starting materials. A new microwave-assisted intramolecular dehydrogenative DA reaction of styrenyl derivatives described herein generates a variety of functionalized cyclopenta[b]naphthalenes that could not be prepared using existing synthetic methods. When compared to conventional heating, microwave irradiation accelerates reaction rates, enhances yields, and limits the formation of undesired byproducts. The utility of this protocol is further demonstrated by the conversion of a DA cycloadduct into a novel solvatochromic fluorescent dye via a Buchwald-Hartwig palladium-catalyzed cross-coupling reaction. Fluorescence spectroscopy, as an informative and sensitive analytical technique, plays a key role in research fields including environmental science, medicine, pharmacology, and cellular biology. Access to a variety of new organic fluorophores provided by the microwave-assisted dehydrogenative DA reaction allows for further advancement in these fields.

Microwave-assisted Intramolecular Dehydrogenative Diels-Alder Reactions for the Synthesis of Functionalized Naphthalenes/Solvatochromic Dyes

PubMed Central

Kocsis, Laura S.; Benedetti, Erica; Brummond, Kay M.

2013-01-01

Functionalized naphthalenes have applications in a variety of research fields ranging from the synthesis of natural or biologically active molecules to the preparation of new organic dyes. Although numerous strategies have been reported to access naphthalene scaffolds, many procedures still present limitations in terms of incorporating functionality, which in turn narrows the range of available substrates. The development of versatile methods for direct access to substituted naphthalenes is therefore highly desirable. The Diels-Alder (DA) cycloaddition reaction is a powerful and attractive method for the formation of saturated and unsaturated ring systems from readily available starting materials. A new microwave-assisted intramolecular dehydrogenative DA reaction of styrenyl derivatives described herein generates a variety of functionalized cyclopenta[b]naphthalenes that could not be prepared using existing synthetic methods. When compared to conventional heating, microwave irradiation accelerates reaction rates, enhances yields, and limits the formation of undesired byproducts. The utility of this protocol is further demonstrated by the conversion of a DA cycloadduct into a novel solvatochromic fluorescent dye via a Buchwald-Hartwig palladium-catalyzed cross-coupling reaction. Fluorescence spectroscopy, as an informative and sensitive analytical technique, plays a key role in research fields including environmental science, medicine, pharmacology, and cellular biology. Access to a variety of new organic fluorophores provided by the microwave-assisted dehydrogenative DA reaction allows for further advancement in these fields. PMID:23609566

Palladium-Catalyzed Asymmetric Allylic Alkylation of 3-Substituted 1 H-Indoles and Tryptophan Derivatives with Vinylcyclopropanes.

PubMed

Trost, Barry M; Bai, Wen-Ju; Hohn, Christoph; Bai, Yu; Cregg, James J

2018-05-30

Vinylcyclopropanes (VCPs) are known to generate 1,3-dipoles with a palladium catalyst that initially serve as nucleophiles to undergo [3 + 2] cycloadditions with electron-deficient olefins. In this report, we reverse this reactivity and drive the 1,3-dipoles to serve as electrophiles by employing 3-alkylated indoles as nucleophiles. This represents the first use of VCPs for the completely atom-economic functionalization of 3-substituted 1 H-indoles and tryptophan derivatives via a Pd-catalyzed asymmetric allylic alkylation (Pd-AAA). Excellent yields and high chemo-, regio-, and enantioselectivities have been realized, providing various indolenine and indoline products. The method is amenable to gram scale and works efficiently with tryptophan derivatives that contain a diketopiperazine or diketomorpholine ring, allowing us to synthesize mollenine A in a rapid and ligand-controlled fashion. The obtained indolenine products bear an imine, an internal olefin, and a malonate motif, giving multiple sites with diverse reactivities for product diversification. Complicated polycyclic skeletons can be conveniently constructed by leveraging this unique juxtaposition of functional groups.

Z-Selective iridium-catalyzed cross-coupling of allylic carbonates and α-diazo esters† †Electronic supplementary information (ESI) available: Full procedures, computational details and characterization data. See DOI: 10.1039/c7sc04283c

PubMed Central

Thomas, Bryce N.; Moon, Patrick J.; Yin, Shengkang; Brown, Alex

2017-01-01

A well-defined Ir–allyl complex catalyzes the Z-selective cross-coupling of allyl carbonates with α-aryl diazo esters. The process overrides the large thermodynamic preference for E-products typically observed in metal-mediated coupling reactions to enable the synthesis of Z,E-dieneoates in good yield with selectivities consistently approaching or greater than 90 : 10. This transformation represents the first productive merger of Ir–carbene and Ir–allyl species, which are commonly encountered intermediates in allylation and cyclopropanation/E–H insertion catalysis. Potentially reactive functional groups (aryl halides, ketones, nitriles, olefins, amines) are tolerated owing to the mildness of reaction conditions. Kinetic analysis of the reaction suggests oxidative addition of the allyl carbonate to an Ir-species is rate-determining. Mechanistic studies uncovered a pathway for catalyst activation mediated by NEt3. PMID:29629093

Palladium pincer complex catalyzed stannyl and silyl transfer to propargylic substrates: synthetic scope and mechanism.

PubMed

Kjellgren, Johan; Sundén, Henrik; Szabó, Kálmán J

2005-02-16

Pincer complex catalyzed substitution of various propargylic substrates could be achieved using tin- and silicon-based dimetallic reagents to obtain propargyl- and allenylstannanes and silanes. These reactions involving chloride, mesylate, and epoxide substrates could be carried out under mild conditions, and therefore many functionalities (such as COOEt, OR, OH, NR, and NAc) are tolerated. It was shown that pincer catalysts with electron-supplying ligands, such as NCN, SCS, and SeCSe complexes, display the highest catalytic activity. The catalytic substitution of secondary propargyl chlorides and primary propargyl chlorides with electron-withdrawing substituents proceeds with high regioselectivity providing the allenyl product. Opening of the propargyl epoxides takes place with an excellent stereo- and regioselectivity to give stereodefined allenylstannanes. Silylstannanes as dimetallic reagents undergo an exclusive silyl transfer to the propargylic substrate affording allenylsilanes with high regioselectivity. According to our mechanistic studies, the key intermediate of the reaction is an organostannane (or silane)-coordinated pincer complex, which is formed from the dimetallic reagent and the corresponding pincer complex catalyst. DFT modeling studies have shown that the trimethylstannyl functionality is transferred to the propargylic substrate in a single reaction step with high allenyl selectivity. Inspection of the TS structures reveals that the trimethylstannyl group transfer is initiated by the attack of the palladium-tin sigma-bond electrons on the propargylic substrate. This is a novel mechanism in palladium chemistry, which is based on the unique topology of the pincer complex catalysts.

Total synthesis of (+)-ileabethoxazole via an iron-mediated Pauson-Khand [2 + 2 + 1] carbocyclization.

PubMed

Williams, David R; Shah, Akshay A

2014-06-18

Studies describe the total synthesis of (+)-ileabethoxazole (1) using a Stille cross-coupling reaction of propargylic stannanes with 5-iodo-1,3-oxazoles to produce 1,1-disubstituted allenes (11). An iron-mediated [2 + 2 + 1] carbocyclization yields a novel cyclopentenone for elaboration to 1. Site-selective palladium insertion reactions allow for regiocontrolled substitutions of the heterocycle. Asymmetric copper hydride reductions are examined, and strategies for the formation of the central aromatic ring are discussed.

Imparting Catalyst-Control upon Classical Palladium-Catalyzed Alkenyl C–H Bond Functionalization Reactions

PubMed Central

Sigman, Matthew S.; Werner, Erik W.

2011-01-01

Conspectus The functional group transformations carried out by the palladium-catalyzed Wacker and Heck reactions are radically different, but they are both alkenyl C-H bond functionalization reactions that have found extensive use in organic synthesis. The synthetic community depends heavily on these important reactions, but selectivity issues arising from control by the substrate, rather than control by the catalyst, have prevented the realization of their full potential. Because of important similarities in the respective selectivity-determining nucleopalladation and β-hydride elimination steps of these processes, we posit that the mechanistic insight garnered through the development of one of these catalytic reactions may be applied to the other. In this Account, we detail our efforts to develop catalyst-controlled variants of both the Wacker oxidation and the Heck reaction to address synthetic limitations and provide mechanistic insight into the underlying organometallic processes of these reactions. In contrast to previous reports, we discovered that electrophilic palladium catalysts with non-coordinating counterions allowed for the use of a Lewis basic ligand to efficiently promote TBHP-mediated Wacker oxidation reactions of styrenes. This discovery led to the mechanistically guided development of a Wacker reaction catalyzed by a palladium complex with a bidentate ligand. This ligation may prohibit coordination of allylic heteroatoms, thereby allowing for the application of the Wacker oxidation to substrates that were poorly behaved under classical conditions. Likewise, we unexpectedly discovered that electrophilic Pd-σ-alkyl intermediates are capable of distinguishing between electronically inequivalent C–H bonds during β-hydride elimination. As a result, we have developed E-styrenyl selective oxidative Heck reactions of previously unsuccessful electronically non-biased alkene substrates using arylboronic acid derivatives. The mechanistic insight gained from the development of this chemistry allowed for the rational design of a similarly E-styrenyl selective classical Heck reaction using aryldiazonium salts and a broad range of alkene substrates. The key mechanistic findings from the development of these reactions provide new insight into how to predictably impart catalyst control in organometallic processes that would otherwise afford complex product mixtures. Given our new understanding, we are optimistic that reactions that introduce increased complexity relative to simple classical processes may now be developed based on our ability to predict the selectivity-determining nucleopalladation and β-hydride elimination steps through catalyst design. PMID:22111756