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Sample records for palladium catalyzed cross-coupling

  1. Recyclable polystyrene-supported siloxane-transfer agent for palladium-catalyzed cross-coupling reactions.

    PubMed

    Nguyen, Minh H; Smith, Amos B

    2014-04-01

    The rational design, synthesis, and validation of a significantly improved insoluble polymer-supported siloxane-transfer agent has been achieved that permits efficient palladium-catalyzed cross-coupling reactions. The cross-linked polystyrene support facilitates product purification with excellent siloxane recycling. Drawbacks of a previous polymer-supported siloxane-transfer agent, relating to reaction efficiency and polymer stability after repeated cycles, have been addressed.

  2. Recyclable Polystyrene-Supported Siloxane-Transfer Agent for Palladium-Catalyzed Cross-Coupling Reactions

    PubMed Central

    2015-01-01

    The rational design, synthesis, and validation of a significantly improved insoluble polymer-supported siloxane-transfer agent has been achieved that permits efficient palladium-catalyzed cross-coupling reactions. The cross-linked polystyrene support facilitates product purification with excellent siloxane recycling. Drawbacks of a previous polymer-supported siloxane-transfer agent, relating to reaction efficiency and polymer stability after repeated cycles, have been addressed. PMID:24661113

  3. Synthesis of hindered biphenyls by sequential non-transition metal-catalyzed reaction/palladium-catalyzed cross-couplings.

    PubMed

    He, Ping; Dong, Cheng-Guo; Hu, Qiao-Sheng

    2008-03-17

    The sequential reaction of 1,2-dihalobenzenes with aryl lithiums followed by palladium-catalyzed cross-coupling reactions with Grignard reagents and arylboronic acids is described. This sequential reaction provides a convenient and expeditious access to tri-ortho substituted biaryl derivatives.

  4. A General Palladium-Catalyzed Hiyama Cross-Coupling Reaction of Aryl and Heteroaryl Chlorides.

    PubMed

    Yuen, On Ying; So, Chau Ming; Man, Ho Wing; Kwong, Fuk Yee

    2016-05-01

    A general palladium-catalyzed Hiyama cross-coupling reaction of aryl and heteroaryl chlorides with aryl and heteroaryl trialkoxysilanes by a Pd(OAc)2 /L2 catalytic system is presented. A newly developed water addition protocol can dramatically improve the product yields. The conjugation of the Pd/L2 system and the water addition protocol can efficiently catalyze a broad range of electron-rich, -neutral, -deficient, and sterically hindered aryl chlorides and heteroaryl chlorides with excellent yields within three hours and the catalyst loading can be down to 0.05 mol % Pd for the first time. Hiyama coupling of heteroaryl chlorides with heteroaryl silanes is also reported for the first time. The reaction can be easily scaled up 200 times (100 mmol) without any degasification and purification of reactants; this facilitates the practical application in routine synthesis.

  5. 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

    2015-04-01

    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). PMID:25794590

  6. 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

    2015-04-01

    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).

  7. Why You Really Should Consider Using Palladium-Catalyzed Cross-Coupling of Silanols and Silanolates

    PubMed Central

    Ambrosi, Andrea

    2015-01-01

    The transition metal-catalyzed cross-coupling of organometallic nucleophiles derived from tin, boron, and zinc with organic electrophiles enjoys a preeminent status among modern synthetic methods for the formation of carbon-carbon bonds. In recent years, organosilanes have emerged as viable alternatives to the conventional reagents, with the added benefits of low cost, low toxicity and high chemical stability. However, silicon-based cross-coupling reactions often require heating in the presence of a fluoride source, which has significantly hampered their widespread acceptance. To address the “fluoride problem”, a new paradigm for palladium-catalyzed, silicon-based cross-coupling reactions has been developed that employs a heretofore underutilized class of silicon reagents, the organosilanols. The use of organosilanols, either in the presence of Brønsted bases or as their silanolate salts, represents an operationally simple and mild alternative to the fluoride-based activation method. Organosilanols are readily available by many well-established methods for introducing carbon-silicon bonds onto alkenes, alkynes, arenes and heteroarenes. Moreover, several different protocols for the generation of alkali metal salts of, vinyl-, alkenyl-, alkynyl-, aryl-, and heteroarylsilanolates have been developed and the advantages of each of these methods have been demonstrated for a number of different coupling classes. This review will describe the development and implementation of cross-coupling reactions of organosilanols and their conjugate bases, silanolates, with a wide variety of substrate classes. In addition, application of these transformations in the total synthesis of complex natural products will also be highlighted. Finally, the unique advantages of organosilicon coupling strategies vis a vis organoboron reagents are discussed. PMID:26478695

  8. Palladium-catalyzed synthesis of indoles via ammonia cross-coupling-alkyne cyclization.

    PubMed

    Alsabeh, Pamela G; Lundgren, Rylan J; Longobardi, Lauren E; Stradiotto, Mark

    2011-06-28

    The synthesis of indoles via the metal-catalyzed cross-coupling of ammonia is reported for the first time; the developed protocol also allows for the unprecedented use of methylamine or hydrazine as coupling partners. These Pd/Josiphos-catalyzed reactions proceed under relatively mild conditions for a range of 2-alkynylbromoarenes.

  9. Transition-metal-catalyzed Suzuki-Miyaura cross-coupling reactions: a remarkable advance from palladium to nickel catalysts.

    PubMed

    Han, Fu-She

    2013-06-21

    In the transition-metal-catalyzed cross-coupling reactions, the use of the first row transition metals as catalysts is much more appealing than the precious metals owing to the apparent advantages such as cheapness and earth abundance. Within the last two decades, particularly the last five years, explosive interests have been focused on the nickel-catalyzed Suzuki-Miyaura reactions. This has greatly advanced the chemistry of transition-metal-catalyzed cross-coupling reactions. Most notably, a broad range of aryl electrophiles such as phenols, aryl ethers, esters, carbonates, carbamates, sulfamates, phosphates, phosphoramides, phosphonium salts, and fluorides, as well as various alkyl electrophiles, which are conventionally challenging, by applying palladium catalysts can now be coupled efficiently with boron reagents in the presence of nickel catalysts. In this review, we would like to summarize the progress in this reaction.

  10. Palladium-catalyzed cross-coupling reactions of 4a,8a-azaboranaphthalene.

    PubMed

    Sun, Feiye; Lv, Lily; Huang, Min; Zhou, Zhaohui; Fang, Xiangdong

    2014-10-01

    A concise and effective three-step synthesis of 4a,8a-azaboranaphthalene (ABN) has been developed in gram scale. Electrophilic aromatic substitution reactions of ABN provide excellent functional-group-tolerant cross-coupling partners in various Pd-catalyzed cross-coupling reactions (e.g., Sonogashira, Suzuki-Miyaura, or Heck reaction). Photophysical, electrochemical, and DFT calculations all suggest a narrowed HOMO-LUMO gap with extended π-conjugation characters in the cross-coupled molecules. The ABN moiety as a new fluorophore has a distinct and selective fluorescence response toward Zn(II) and Cd(II) ions, demonstrating great potential for the ABN structural motif in fluorescent chemosensors.

  11. Palladium-catalyzed decarboxylative cross-coupling reactions: a route for regioselective functionalization of coumarins.

    PubMed

    Jafarpour, Farnaz; Zarei, Samaneh; Olia, Mina Barzegar Amiri; Jalalimanesh, Nafiseh; Rahiminejadan, Soraya

    2013-04-01

    A straightforward, regioselective, and step-economical ligand-free palladium-catalyzed decarboxylative functionalization of coumarin-3-carboxylic acids is devised. This protocol is compatible with a wide variety of electron-donating and -withdrawing substituents and allows for construction of various biologically important π-electron extended coumarins. PMID:23445254

  12. 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

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

    PubMed

    McMahon, Caitlin M; Alexanian, Erik J

    2014-06-01

    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.

  14. Palladium-Catalyzed Thioetherification of Quinolone Derivatives via Decarboxylative C-S Cross-Couplings.

    PubMed

    Xia, Chengcai; Wei, Zhenjiang; Yang, Yong; Yu, Wenbo; Liao, Hanxiao; Shen, Chao; Zhang, Pengfei

    2016-02-01

    A highly efficient and practical procedure for palladium-catalyzed direct thioetherification of quinolone derivatives with diaryl disulfides through decarboxylative C-S coupling has been established. The reaction could proceed smoothly under air in the presence of Pd(OAc)2 and Ag2 CO3 in DMSO. This protocol provides an appealing alternative to existing approaches to construct aryl sulfides of quinolone derivatives, which may be used as key intermediates in the synthesis of drug candidates.

  15. Application of palladium-catalyzed carboxyl anhydride-boronic acid cross coupling in the synthesis of novel bile acids analogs with modified side chains.

    PubMed

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

    2015-09-01

    Palladium-catalyzed cross coupling of 4-methoxycarbonyl phenyboronic acid with acetylated bile acids in which the carboxyl functions was activated by formation of a mixed anhydride with pivalic anhydride afforded the cross coupled compounds, which were converted in novel side chain modified bile acids by one pot carbonyl reduction/removal of the protecting acetyl groups by Wolff-Kishner reduction. Unambiguous assignments of the NMR signals and crystal characterization of the heretofore unknown compounds are provided.

  16. Direct preparation of N-quaternized and N-oxidized polycyclic azines by palladium-catalyzed cross-coupling. An unequivocal isomer synthesis

    SciTech Connect

    Zoltewicz, J.A.; Cruskie, M.P. Jr.; Dill, C.D.

    1995-01-13

    The authors report several examples of unequivocal isomer preparations using palladium-catalyzed cross-coupling to yield N-oxides and N-quaternized polycyclic azines. This approach serves as a model for such syntheses where selective N-quaternization, N-oxidation, or other types of N-functionalization of several rings is now possible in a regioncontrolled manner.

  17. Palladium-catalyzed cross-coupling between vinyl halides and tert-butyl carbazate: first general synthesis of the unusual N-Boc-N-alkenylhydrazines.

    PubMed

    Barluenga, José; Moriel, Patricia; Aznar, Fernando; Valdés, Carlos

    2007-01-18

    N-Boc-N-alkenylhydrazines, an almost unknown type of compounds, have been prepared with high to moderate yields via palladium-catalyzed cross-coupling between alkenyl halides and tert-butyl carbazate. The present methodology represents the first general way to access this highly functionalized and unusual type of hydrazines. [reaction: see text].

  18. 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

    2014-11-01

    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. PMID:25327183

  19. Palladium-catalyzed dehydrogenation/oxidative cross-coupling sequence of β-heteroatom-substituted ketones.

    PubMed

    Moon, Youngtaek; Kwon, Daeil; Hong, Sungwoo

    2012-11-01

    Concise and selective: the title one-pot sequence allows formation of the enone functionality and subsequent cross-coupling. The process provides access to highly functionalized cyclic enolones and enaminones from readily accessible β-heteroatom-substituted cyclic ketones. PMID:23038616

  20. Accessing 2-(Hetero)arylmethyl-, -allyl-, and -propargyl-2,1-borazaronaphthalenes: Palladium-Catalyzed Cross-Couplings of 2-(Chloromethyl)-2,1-borazaronaphthalenes

    PubMed Central

    2015-01-01

    The synthesis of 2-(chloromethyl)-2,1-borazaronaphthalene has provided an opportunity to expand dramatically the functionalization of the azaborines. This azaborinyl building block can serve as the electrophile in palladium-catalyzed cross-coupling reactions to form sp3–sp and sp3–sp2 bonds. The cross-coupling reactions of 2-(chloromethyl)-2,1-borazaronaphthalene with potassium (hetero)aryl- and alkenyltrifluoroborates as well as terminal alkynes provides access to a variety of novel azaborines, allowing a library of pseudobenzylic substituted azaborines to be prepared from one common starting material. PMID:25365512

  1. Triazole-based monophosphine ligands for palladium-catalyzed cross-coupling reactions of aryl chlorides.

    PubMed

    Dai, Qian; Gao, Wenzhong; Liu, Duan; Kapes, Lea M; Zhang, Xumu

    2006-05-12

    A variety of triazole-based monophosphines (ClickPhos) have been prepared via efficient 1,3-dipolar cycloaddition of readily available azides and acetylenes. Their palladium complexes provided excellent yields in the amination reactions and Suzuki-Miyaura coupling reactions of unactivated aryl chlorides. Ligand 7i, which has a 2,6-dimethoxybenzene moiety, provided good results in Suzuki-Miyaura reaction to form hindered biaryls. A CAChe model for the Pd/7i complex shows that the likelihood of a Pd-arene interaction might be a rationale for its high catalytic reactivity.

  2. 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.

  3. Palladium-Catalyzed Cross Coupling of Secondary and Tertiary Alkyl Bromides with a Nitrogen Nucleophile

    PubMed Central

    2016-01-01

    We report a new class of catalytic reaction: the thermal substitution of a secondary and or tertiary alkyl halide with a nitrogen nucleophile. The alkylation of a nitrogen nucleophile with an alkyl halide is a classical method for the construction of C–N bonds, but traditional substitution reactions are challenging to achieve with a secondary and or tertiary alkyl electrophile due to competing elimination reactions. A catalytic process could address this limitation, but thermal, catalytic coupling of alkyl halides with a nitrogen nucleophile and any type of catalytic coupling of an unactivated tertiary alkyl halide with a nitrogen nucleophile are unknown. We report the coupling of unactivated secondary and tertiary alkyl bromides with benzophenone imines to produce protected primary amines in the presence of palladium ligated by the hindered trialkylphosphine Cy2t-BuP. Mechanistic studies indicate that this amination of alkyl halides occurs by a reversible reaction to form a free alkyl radical. PMID:27725963

  4. Surveying sterically demanding N-heterocyclic carbene ligands with restricted flexibility for palladium-catalyzed cross-coupling reactions.

    PubMed

    Würtz, Sebastian; Glorius, Frank

    2008-11-18

    Heterocyclic carbenes (NHCs), especially monodentate ones, have become the ligand of choice for many transition-metal-catalyzed transformations. They generally form highly stable complexes, have strong sigma-donor character, and have a unique shape that can be used to generate sterically demanding ligands.In this Account, we survey recent developments in the design and synthesis of some sterically demanding NHCs with a particularly strong influence on the metal's coordination sphere. We show the successful and insightful application of these ligands in transition-metal catalysis. First, we discuss methods for determining and classifying the electronic and steric properties of NHCs. In addition, we present data on the most important NHC ligands.The selective variation of either electronic or steric parameters of NHCs, and therefore of the catalyst, allows for the optimization of the reaction. Thus, we prepared several series of differentially substituted NHC derivatives. However, because the substituents varied were not directly connected to the carbene carbon, it was difficult to induce a large electronic variation. In contrast, an independent variation of the ligands' steric properties was more straightforward. We highlight three different classes of very sterically demanding NHCs that allow this kind of a steric variation: imidazo[1,5-a]pyridine-3-ylidenes, bioxazoline-derived carbenes (IBiox), and cyclic (alkyl)(amino)carbenes (CAAC).These latter NHC ligands can facilitate a number of challenging cross-coupling reactions. Successful transformations often require a monoligated palladium complex as the catalytically active species, and the sterically demanding NHC ligand favors this monoligated complex. In addition, the electron-rich NHC facilitates difficult oxidative addition steps. Moreover, the conformational flexibility of the ligands can facilitate the formation of catalytically active species and hemilabile interactions, such as agostic or anagostic bonds

  5. Metal-Catalyzed Cross-Coupling Reactions for Indoles

    NASA Astrophysics Data System (ADS)

    Li, Jie Jack; Gribble, Gordon W.

    Metal-catalyzed cross-coupling reactions for indoles are reviewed. Palladium-catalyzed cross-coupling reactions are the most widely explored and applied of all metal-catalyzed cross-coupling reactions. Applications of Kumada coupling, Negishi coupling, Suzuki coupling, Stille coupling, Sonogashira reaction, the Heck reaction, carbonylation, and C-N bond formation reactions in indoles are summarized. In addition, other transition metal-catalyzed cross-coupling reactions using copper, rhodium, iron, and nickel in indole synthesis are also discussed.

  6. Kinetic Studies on the Palladium(II)-Catalyzed Oxidative Cross-Coupling of Thiophenes with Arylboron Compounds and Their Mechanistic Implications.

    PubMed

    Schnapperelle, Ingo; Breitenlechner, Stefan; Bach, Thorsten

    2015-12-01

    Reaction orders for the key components in the palladium(II)-catalyzed oxidative cross-coupling between phenylboronic acid and ethyl thiophen-3-yl acetate were obtained by the method of initial rates. It turned out that the reaction rate not only depended on the concentration of palladium trifluoroacetate (reaction order: 0.97) and phenylboronic acid (reaction order: 1.26), but also on the concentration of the thiophene (reaction order: 0.55) and silver oxide (reaction order: -1.27). NMR spectroscopy titration studies established the existence of 1:1 complexes between the silver salt and both phenylboronic acid and ethyl thiophen-3-yl acetate. A low inverse kinetic isotope effect (kH /kD =0.93) was determined upon employing the 4-deuterated isotopomer of ethyl thiophen-3-yl acetate and monitoring its reaction to the 4-phenyl-substituted product. A Hammett analysis performed with para-substituted 2-phenylthiophenes gave a negative ρ value for oxidative cross-coupling with phenylboronic acid. Based on the kinetic data and additional evidence, a mechanism is suggested that invokes transfer of the phenyl group from phenylboronic acid to a 1:1 complex of palladium trifluoroacetate and thiophene as the rate-determining step. Proposals for the structure of relevant intermediates are made and discussed. PMID:26515114

  7. 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

  8. Palladium-catalyzed cross-coupling reactions of organosilanols and their salts: practical alternatives to boron- and tin-based methods.

    PubMed

    Denmark, Scott E; Regens, Christopher S

    2008-11-18

    In the panoply of modern synthetic methods for forming carbon-carbon and carbon-heteroatom bonds, the transition metal-catalyzed cross-coupling of organometallic nucleophiles with organic electrophiles enjoys a preeminent status. The preparative utility of these reactions is, in large measure, a consequence of the wide variety of organometallic donors that have been conscripted into service. The most common of these reagents are organic derivatives of tin, boron, and zinc, which each possess unique advantages and shortcomings. Because of their low cost, low toxicity, and high chemical stability, organosilanes have emerged as viable alternatives to the conventional reagents in recent years. However, unlike the tin- and zinc-based reactions, which require no activation, or the boron-based reactions, which require only heating with mild bases, silicon-based cross-coupling reactions often require heating in the presence of a fluoride source; this has significantly hampered the widespread acceptance of organosilanes. To address the "fluoride problem", we have introduced a new paradigm for palladium-catalyzed, silicon-based cross-coupling reactions that employs organosilanols, a previously underutilized class of silicon reagents. The use of organosilanols either in the presence of Brønsted bases or as their silanolate salts represents a simple and mild alternative to the classic fluoride-based activation method. Organosilanols are easily available by many well-established methods for introducing carbon-silicon bonds onto alkenes, alkynes, and arenes and heteroarenes. Moreover, we have developed four different protocols for the generation of alkali metal salts of vinyl-, alkenyl-, alkynyl-, aryl-, and heteroarylsilanolates: (1) reversible deprotonation with weak Brønsted bases, (2) irreversible deprotonation with strong Brønsted bases, (3) isolation of the salts from irreversible deprotonation, and (4) silanolate exchange with disiloxanes. We have demonstrated the

  9. Palladium-catalyzed C(sp3)-H arylation of diarylmethanes at room temperature: synthesis of triarylmethanes via deprotonative-cross-coupling processes.

    PubMed

    Zhang, Jiadi; Bellomo, Ana; Creamer, Andrea D; Dreher, Spencer D; Walsh, Patrick J

    2012-08-22

    Although metal-catalyzed direct arylation reactions of non- or weakly acidic C-H bonds have recently received much attention, chemists have relied heavily on substrates with appropriately placed directing groups to steer reactivity. To date, examples of intermolecular arylation of unactivated C(sp(3))-H bonds in the absence of a directing group remain scarce. We report herein the first general, high-yielding, and scalable method for palladium-catalyzed C(sp(3))-H arylation of simple diarylmethane derivatives with aryl bromides at room temperature. This method facilitates access to a variety of sterically and electronically diverse hetero- and nonheteroaryl-containing triarylmethanes, a class of compounds with various applications and interesting biological activity. Key to the success of this approach is an in situ metalation of the substrate via C-H deprotonation under catalytic cross-coupling conditions, which is referred to as a deprotonative-cross-coupling process (DCCP). Base and catalyst identification were performed by high-throughput experimentation (HTE) and led to a unique base/catalyst combination [KN(SiMe(3))(2)/Pd-NiXantphos] that proved to efficiently promote the room-temperature DCCP of diarylmethanes. Additionally, the DCCP exhibits remarkable chemoselectivity in the presence of substrates that are known to undergo O-, N-, enolate-, and C(sp(2))-H arylation.

  10. Widely applicable synthesis of enantiomerically pure tertiary alkyl-containing 1-alkanols by zirconium-catalyzed asymmetric carboalumination of alkenes and palladium- or copper-catalyzed cross-coupling.

    PubMed

    Xu, Shiqing; Lee, Ching-Tien; Wang, Guangwei; Negishi, Ei-ichi

    2013-08-01

    A highly enantioselective and widely applicable method for the synthesis of various chiral 2-alkyl-1-alkanols, especially those of feeble chirality, has been developed. It consists of zirconium-catalyzed asymmetric carboalumination of alkenes (ZACA), lipase-catalyzed acetylation, and palladium- or copper-catalyzed cross-coupling. By virtue of the high selectivity factor (E) associated with iodine, either (S)- or (R)-enantiomer of 3-iodo-2-alkyl-1-alkanols (1), prepared by ZACA reaction of allyl alcohol, can be readily purified to the level of ≥99% ee by lipase-catalyzed acetylation. A variety of chiral tertiary alkyl-containing alcohols, including those that have been otherwise difficult to prepare, can now be synthesized in high enantiomeric purity by Pd- or Cu-catalyzed cross-coupling of (S)-1 or (R)-2 for introduction of various primary, secondary, and tertiary carbon groups with retention of all carbon skeletal features. These chiral tertiary alkyl-containing alcohols can be further converted into the corresponding acids with full retention of the stereochemistry. The synthetic utility of this method has been demonstrated in the highly enantioselective (≥99% ee) and efficient syntheses of (R)-2-methyl-1-butanol and (R)- and (S)-arundic acids.

  11. Palladium-phosphinous acid complexes catalyzed Suzuki cross-coupling reaction of heteroaryl bromides with phenylboronic acid in water/alcoholic solvents.

    PubMed

    Li, Ben; Wang, Cuiping; Chen, Guang; Zhang, Zhiqiang

    2013-06-01

    Highly active, air-stable and water-soluble palladium-phosphinous acid complexes have been applied to Suzuki cross-coupling reaction of heteroaryl bromides under mild conditions in water/alcoholic solvents. Suzuki cross-coupling reaction of heteroaryl bromides with phenylboronic acid occurred efficiently using palladium phosphinous acid complexes (POPd) and phase transfer catalyst (tetrabutylammonium bromide and polyethylene glycol) in water/ethanol mixture, water/propanol mixture and neat water respectively, the corresponding yields of cross-coupling heteroaryl-aryls were satisfied. The tert-butyl substituted ligand di-tert-butylphosphino in combination with POPd was found to be more active than the same family derived catalysts dipalladium complexes POPd1 and POPd2, and other two kinds of Pd-catalysts Pd(PPh3)4 and Pd2(dba)3. The mechanism of Suzuki cross-coupling reaction between heteroaryl bromides and phenylboronic acid in water was proposed with respect to the key role of phase transfer catalyst on the transmetallation step. Compared with other solid phase transfer catalysts, TBAB was tested as the ideal one. The alkalinity of base and the molar proportion between POPd and TBAB were investigated in water and alcoholic solvents. Notably, in the presence of TBAB adding alcoholic solvents into water enhanced the yields of target products. However in terms of the liquid phase transfer catalyst of PEGs, mixing water into PEGs could slightly decrease the yields with respect to the water free PEGs bulk phase, which was probably due to the homogenous liquid conditions in pure PEGs and weak interactions between PEGs and heteroaryl bromide molecules in water depending on their molecular chain lengths.

  12. Suzuki–Miyaura cross-coupling reaction of 1-aryltriazenes with arylboronic acids catalyzed by a recyclable polymer-supported N-heterocyclic carbene–palladium complex catalyst

    PubMed Central

    Nan, Guangming; Ren, Fang

    2010-01-01

    Summary The Suzuki–Miyaura cross-coupling reaction of 1-aryltriazenes with arylboronic acids catalyzed by a recyclable polymer-supported Pd–NHC complex catalyst has been realized for the first time. The polymer-supported catalyst can be re-used several times still retaining high activity for this transformation. Various aryltriazenes were investigated as electrophilic substrates at room temperature to give biaryls in good to excellent yields and showed good chemoselectivity over aryl halides in the reactions. PMID:20703375

  13. Polymer-supported siloxane transfer agents for Pd-catalyzed cross-coupling reactions.

    PubMed

    Nguyen, Minh H; Smith, Amos B

    2013-08-16

    The design, synthesis, and validation of a ring-opening metathesis polymerization (ROMP) polymer supporting siloxane transfer agents have been achieved that permit efficient palladium-catalyzed cross-coupling reactions. The solubility properties of the polymer facilitate not only product purification but also polymer recycling without significant loss of cross-coupling activity.

  14. Pd-catalyzed cross-coupling reactions of alkyl halides.

    PubMed

    Kambe, Nobuaki; Iwasaki, Takanori; Terao, Jun

    2011-10-01

    Cross-coupling reactions have become indispensable tools for creating carbon-carbon (or heteroatom) bonds in organic synthesis. Like in other important transition metal catalyzed reactions, such as metathesis, addition, and polymerization, unsaturated compounds are usually employed as substrates for cross-coupling reactions. However during the past decade, a great deal of effort has been devoted to the use of alkyl halides as saturated compounds in cross-coupling reactions, which has resulted in significant progress in this undeveloped area by introducing new effective ligands. Many useful catalytic systems are now available for synthetic transformations based on C(sp(3))-C(sp(3)), C(sp(3))-C(sp(2)) and C(sp(3))-C(sp) bond formation as complementary methods to conventional C(sp(2))-C(sp(2)), C(sp(2))-C(sp) and C(sp)-C(sp) coupling. This tutorial review summarizes recent advances in cross-coupling reactions of alkyl halides and pseudohalides catalyzed by a palladium complex.

  15. Diversification of edaravone via palladium-catalyzed hydrazine cross-coupling: Applications against protein misfolding and oligomerization of beta-amyloid.

    PubMed

    MacLean, Mark A; Diez-Cecilia, Elena; Lavery, Christopher B; Reed, Mark A; Wang, Yanfei; Weaver, Donald F; Stradiotto, Mark

    2016-01-01

    N-Aryl derivatives of edaravone were identified as potentially effective small molecule inhibitors of tau and beta-amyloid aggregation in the context of developing disease-modifying therapeutics for Alzheimer's disease (AD). Palladium-catalyzed hydrazine monoarylation protocols were then employed as an expedient means of preparing a focused library of 21 edaravone derivatives featuring varied N-aryl substitution, thereby enabling structure-activity relationship (SAR) studies. On the basis of data obtained from two functional biochemical assays examining the effect of edaravone derivatives on both fibril and oligomer formation, it was determined that derivatives featuring an N-biaryl motif were four-fold more potent than edaravone.

  16. The promise and challenge of iron-catalyzed cross coupling.

    PubMed

    Sherry, Benjamin D; Fürstner, Alois

    2008-11-18

    Transition metal catalysts, particularly those derived from the group VIII-X metals, display remarkable efficiency for the formation of carbon-carbon and carbon-heteroatom bonds through the reactions of suitable nucleophiles with organic electrophilic partners. Within this subset of the periodic table, palladium and nickel complexes offer the broadest utility, while additionally providing the deepest mechanistic insight into thus-termed "cross-coupling reactions". The mammoth effort devoted to palladium and nickel catalysts over the past 30 years has somewhat obscured reports of alternative metal complexes in this arena. As cross-coupling reactions have evolved into a critical support for modern synthetic chemistry, the search for alternative catalysts has been taken up with renewed vigor.When the current generation of synthetic chemists reflects back to the origins of cross coupling for inspiration, the well-documented effect of iron salts on the reactivity of Grignard reagents with organic electrophiles surfaces as a fertile ground for alternative catalyst development. Iron possesses the practical benefits more befitting an alkali or alkaline earth metal, while displaying the unique reactivity of a d-block element. Therefore the search for broadly applicable iron catalysts for cross coupling is an increasingly important goal in modern synthetic organic chemistry.This Account describes the evolution of iron-catalyzed cross coupling from its inception in the work of Kochi to the present. Specific emphasis is placed on reactivity and synthetic applications, with selected examples from acyl-, alkenyl-, aryl-, and alkyl halide/pseudohalide cross coupling included. The typical reaction partners are Grignard reagents, though organomanganese, -copper, and -zinc derivatives have also been used in certain cases. Such iron-catalyzed processes occur very rapidly even at low temperature and therefore are distinguished by broad functional group compatibility. Furthermore

  17. Symmetrical bisquinolones via metal-catalyzed cross-coupling and homocoupling reactions.

    PubMed

    Hashim, Jamshed; Glasnov, Toma N; Kremsner, Jennifer M; Kappe, C Oliver

    2006-02-17

    Functionalized 4,4'-bisquinolones can be efficiently synthesized by microwave-assisted palladium(0)-catalyzed one-pot borylation/Suzuki cross-coupling reactions or via nickel(0)-mediated homocouplings of 4-chloroquinolin-2(1H)-one precursors. Both methods are also applicable to other types of symmetrical biaryls.

  18. Nickel-Catalyzed Reductive Cross-Coupling of Aryl Bromides with Alkyl Bromides: Et3N as the Terminal Reductant.

    PubMed

    Duan, Zhengli; Li, Wu; Lei, Aiwen

    2016-08-19

    Reductive cross-coupling has emerged as a direct method for the construction of carbon-carbon bonds. Most cobalt-, nickel-, and palladium-catalyzed reductive cross-coupling reactions to date are limited to stoichiometric Mn(0) or Zn(0) as the reductant. One nickel-catalyzed cross-coupling paradigm using Et3N as the terminal reductant is reported. By using this photoredox catalysis and nickel catalysis approach, a direct Csp(2)-Csp(3) reductive cross-coupling of aryl bromides with alkyl bromides is achieved under mild conditions without stoichiometric metal reductants. PMID:27472556

  19. Well-defined N-heterocyclic carbenes-palladium(II) precatalysts for cross-coupling reactions.

    PubMed

    Marion, Nicolas; Nolan, Steven P

    2008-11-18

    Metal-catalyzed cross-coupling reactions, notably those permitting C-C bond formation, have witnessed a meteoritic development and are now routinely employed as a powerful synthetic tool both in academia and in industry. In this context, palladium is arguably the most studied transition metal, and tertiary phosphines occupy a preponderant place as ancillary ligands. Seriously challenging this situation, the use of N-heterocyclic carbenes (NHCs) as alternative ligands in palladium-catalyzed cross-coupling reactions is rapidly gaining in popularity. These two-electron donor ligands combine strong sigma-donating properties with a shielding steric pattern that allows for both stabilization of the metal center and enhancement of its catalytic activity. As a result, the number of well-defined NHC-containing palladium(II) complexes is growing, and their use in coupling reactions is witnessing increasing interest. In this Account, we highlight the advantages of this family of palladium complexes and review their synthesis and applications in cross-coupling chemistry. They generally exhibit high stability, allowing for indefinite storage and easy handling. The use of well-defined complexes permits a strict control of the Pd/ligand ratio (optimally 1/1), avoiding the use of excess costly ligand that usually requires end-game removal. Furthermore, it partly removes the "black box" character often associated with cross-coupling chemistry and catalyst formation. In the present Account, four main classes of NHC-containing palladium(II) complexes will be presented: palladium dimers with bridging halogens, palladacycles, palladium acetates and acetylacetonates, and finally pi-allyl complexes. These additional ligands are best described as a protecting shell that will be discarded going from the palladium(II) precatalyst to the palladium(0) true catalyst. The synthesis of all these precatalysts generally requires simple and short synthetic procedures. Their catalytic activity in

  20. Palladium-Catalyzed C(sp3)–H Arylation of N-Boc Benzylalkylamines via a Deprotonative Cross-Coupling Process

    PubMed Central

    Hussain, Nusrah; Kim, Byeong-Seon; Walsh, Patrick J.

    2016-01-01

    Diarylmethylamines are key intermediates and products in the pharmaceutical industry. Herein we disclose a novel method toward the synthesis of these important compounds via C–H functionalization. Presented is a reversible deprotonation of N-Boc benzylalkylamines at the benzylic C–H with in situ arylation by a NiXant-Phos-based palladium catalyst (50–93% yield, 29 examples). The method is also successful with N-Boc-tetrahydroisoquinolines. The advantages of this method are it avoids strong bases, low temperatures, and the need to transmetallate to main group metals for the coupling. PMID:26129922

  1. Gold-catalyzed homogeneous oxidative cross-coupling reactions.

    PubMed

    Zhang, Guozhu; Peng, Yu; Cui, Li; Zhang, Liming

    2009-01-01

    Oxidizing gold? A gold(I)/gold(III) catalytic cycle is essential for the first oxidative cross-coupling reaction in gold catalysis. By using Selectfluor for gold(I) oxidation, this chemistry reveals the synthetic potential of incorporating gold(I)/gold(III) catalytic cycles into contemporary gold chemistry and promises a new area of gold research by merging powerful gold catalysis and oxidative metal-catalyzed cross-coupling reactions.

  2. Iron-Catalyzed Cross-Coupling of Alkenyl Acetates.

    PubMed

    Gärtner, Dominik; Stein, André Luiz; Grupe, Sabine; Arp, Johannes; Jacobi von Wangelin, Axel

    2015-09-01

    Stable C-O linkages are generally unreactive in cross-coupling reactions which mostly employ more electrophilic halides or activated esters (triflates, tosylates). Acetates are cheap and easily accessible electrophiles but have not been used in cross-couplings because the strong C-O bond and high propensity to engage in unwanted acetylation and deprotonation. Reported herein is a selective iron-catalyzed cross-coupling of diverse alkenyl acetates, and it operates under mild reaction conditions (0 °C, 2 h) with a ligand-free catalyst (1-2 mol%). PMID:26184455

  3. Photoredox Catalysis in Nickel-Catalyzed Cross-Coupling.

    PubMed

    Cavalcanti, Livia N; Molander, Gary A

    2016-08-01

    The traditional transition metal-catalyzed cross-coupling reaction, although well suited for C(sp2)-C(sp2) cross-coupling, has proven less amenable toward coupling of C(sp3)-hybridized centers, particularly using functional group tolerant reagents and reaction conditions. The development of photoredox/Ni dual catalytic methods for cross-coupling has opened new vistas for the construction of carbon-carbon bonds at C(sp3)-hybridized centers. In this chapter, a general outline of the features of such processes is detailed. PMID:27573391

  4. Cross coupling of dialkylmagnesium derivatives with allylic compounds catalyzed by copper salts

    SciTech Connect

    Ibragimov, A.G.; Dzhemilev, U.M.; Saraev, R.A.

    1985-07-20

    The reaction of allylic compounds with Grignard reagents catalyzed by salts of copper, nickel, iron and cobalt, titanium and palladium is a simple and efficient method for the preparation of unsaturated hydrocarbons. However, information concerning the use of dialkylmagnesium derivatives, which are more reactive than Grignard reagents, is extremely limited in these reactions. To continue a study of the cross-coupling of allylic compounds with dialkylmagnesium derivatives in an effort to expand the scope of this reaction and to elucidate the effect of the R/sub 2/Mg reagent structure on its reactivity, the authors investigated the reaction of dialkylmagnesium and diarlmagnesium reagents with allylic ethers and esters, thioethers, and amines, by the action of transition metal salts. This work demonstrates the feasibility of the preparation of unsaturated hydrocarbons of given structure by the cross-coupling of dialkylmagnesium derivatives with functional allylic compounds by the action of catalytic amounts of copper complexes.

  5. Carbon-carbon cross coupling reactions in ionic liquids catalysed by palladium metal nanoparticles.

    PubMed

    Prechtl, Martin H G; Scholten, Jackson D; Dupont, Jairton

    2010-05-12

    A brief summary of selected pioneering and mechanistic contributions in the field of carbon-carbon cross-coupling reactions with palladium nanoparticles (Pd-NPs) in ionic liquids (ILs) is presented. Five exemplary model systems using the Pd-NPs/ILs approach are presented: Heck, Suzuki, Stille, Sonogashira and Ullmann reactions which all have in common the use of ionic liquids as reaction media and the use of palladium nanoparticles as reservoir for the catalytically active palladium species.

  6. Atom-efficient metal-catalyzed cross-coupling reaction of indium organometallics with organic electrophiles.

    PubMed

    Pérez, I; Sestelo, J P; Sarandeses, L A

    2001-05-01

    The novel metal-catalyzed cross-coupling reaction of indium organometallics with organic electrophiles is described. Triorganoindium compounds (R(3)In) containing alkyl, vinyl, aryl, and alkynyl groups are efficiently prepared from the corresponding lithium or magnesium organometallics by reaction with indium trichloride. The cross-coupling reaction of R(3)In with aryl halides and pseudohalides (iodide 2, bromide 5, and triflate 4), vinyl triflates, benzyl bromides, and acid chlorides proceeds under palladium catalysis in excellent yields and with high chemoselectivity. Indium organometallics also react with aryl chlorides as under nickel catalysis. In the cross-coupling reaction the triorganoindium compounds transfer, in a clear example of atom economy, all three of the organic groups attached to the metal, as shown by the necessity of using only 34 mol % of indium. The feasibility of using R(3)In in reactions with different electrophiles, along with the high yields and chemoselectivities obtained, reveals indium organometallics to be useful alternatives to other organometallics in cross-coupling reactions.

  7. Palladium-catalyzed modification of unprotected nucleosides, nucleotides, and oligonucleotides.

    PubMed

    Shaughnessy, Kevin H

    2015-05-22

    Synthetic modification of nucleoside structures provides access to molecules of interest as pharmaceuticals, biochemical probes, and models to study diseases. Covalent modification of the purine and pyrimidine bases is an important strategy for the synthesis of these adducts. Palladium-catalyzed cross-coupling is a powerful method to attach groups to the base heterocycles through the formation of new carbon-carbon and carbon-heteroatom bonds. In this review, approaches to palladium-catalyzed modification of unprotected nucleosides, nucleotides, and oligonucleotides are reviewed. Polar reaction media, such as water or polar aprotic solvents, allow reactions to be performed directly on the hydrophilic nucleosides and nucleotides without the need to use protecting groups. Homogeneous aqueous-phase coupling reactions catalyzed by palladium complexes of water-soluble ligands provide a general approach to the synthesis of modified nucleosides, nucleotides, and oligonucleotides.

  8. 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

  9. 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

  10. 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

  11. Ruthenium-Catalyzed Cross-Coupling of Maleimides with Alkenes.

    PubMed

    Morita, Tomohiro; Akita, Mitsutoshi; Satoh, Tetsuya; Kakiuchi, Fumitoshi; Miura, Masahiro

    2016-09-16

    The cross-coupling of maleimides with electron-deficient alkenes such as acrylates proceeds smoothly under ruthenium catalysis. This unique C-C coupling provides a simple, straightforward synthetic method for preparing alkylidene succinimide derivatives. PMID:27571229

  12. Mechanistic insights into nickamine-catalyzed alkyl-alkyl cross-coupling reactions.

    PubMed

    Breitenfeld, Jan; Hu, Xile

    2014-01-01

    Within the last decades the transition metal-catalyzed cross-coupling of non-activated alkyl halides has significantly progressed. Within the context of alkyl-alkyl cross-coupling, first row transition metals spanning from iron, over cobalt, nickel, to copper have been successfully applied to catalyze this difficult reaction. The mechanistic understanding of these reactions is still in its infancy. Herein we outline our latest mechanistic studies that explain the efficiency of nickel, in particular nickamine-catalyzed alkyl-alkyl cross-coupling reactions.

  13. Heteroaromatic sulfonates and phosphates as electrophiles in iron-catalyzed cross-couplings.

    PubMed

    Gøgsig, Thomas M; Lindhardt, Anders T; Skrydstrup, Troels

    2009-11-01

    Employment of heteroaromatic tosylates and phosphates as suitable electrophiles in iron-catalyzed cross-coupling reactions with alkyl Grignard reagents is reported. These reactions are performed at low temperature allowing good functional group tolerance and full conversion is achieved within minutes. In addition, an aryl-aryl cross-coupling utilizing a heteroaryl sulfamate electrophile is reported.

  14. Applications of and alternatives to pi-electron-deficient azine organometallics in metal catalyzed cross-coupling reactions.

    PubMed

    Campeau, Louis-Charles; Fagnou, Keith

    2007-07-01

    While the use of pi-deficient azine halides in palladium catalyzed cross-coupling reactions is common, the use of pi-electron deficient azine organometallics has been less intensively examined. In recent years, important advances have been made that are beginning to address this deficiency and need. The purpose of this tutorial review is to highlight and discuss the innovations that facilitate the synthesis of azine-containing biaryls with a focus on the pyridine structural motif. Given the number of important compounds which exhibit azine-heterobiaryls and the wide use of cross-coupling methods in their synthesis, this review should be of interest among synthetic organic chemists and organometallic chemists alike.

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

    PubMed

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

    2014-12-01

    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(sp(3)) coupling.

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

    PubMed

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

    2014-12-01

    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(sp(3)) coupling. PMID:25420218

  17. Mechanistic Studies of Gold and Palladium Cooperative Dual-Catalytic Cross-Coupling Systems

    PubMed Central

    Al-Amin, Mohammad; Roth, Katrina E.; Blum, Suzanne A.

    2014-01-01

    Double-label crossover, modified-substrate, and catalyst comparison experiments in the gold and palladium dual-catalytic rearrangement/cross-coupling of allenoates were performed in order to probe the mechanism of this reaction. The results are consistent with a cooperative catalysis mechanism whereby 1) gold activates the substrate prior to oxidative addition by palladium, 2) gold acts as a carbophilic rather than oxophilic Lewis acid, 3) competing olefin isomerization is avoided, 4) gold participates beyond the first turnover and therefore does not serve simply to generate the active palladium catalyst, and 5) single-electron transfer is not involved. These experiments further demonstrate that the cooperativity of both gold and palladium in the reaction is essential because significantly lower to zero conversion is achieved with either metal alone in comparison studies that examined multiple potential gold, palladium, and silver catalysts and precatalysts. Notably, employment of the optimized cocatalysts, PPh3AuOTf and Pd2dba3, separately (i.e., only Au or only Pd) results in zero conversion to product at all monitored time points compared to quantitative conversion to product when both are present in cocatalytic reactions. PMID:24757581

  18. Iron-Catalyzed C-C Cross-Couplings Using Organometallics.

    PubMed

    Guérinot, Amandine; Cossy, Janine

    2016-08-01

    Over the last decades, iron-catalyzed cross-couplings have emerged as an important tool for the formation of C-C bonds. A wide variety of alkenyl, aryl, and alkyl (pseudo)halides have been coupled to organometallic reagents, the most currently used being Grignard reagents. Particular attention has been devoted to the development of iron catalysts for the functionalization of alkyl halides that are generally challenging substrates in classical cross-couplings. The high functional group tolerance of iron-catalyzed cross-couplings has encouraged organic chemists to use them in the synthesis of bioactive compounds. Even if some points remain obscure, numerous studies have been carried out to investigate the mechanism of iron-catalyzed cross-coupling and several hypotheses have been proposed. PMID:27573401

  19. Pd(II)-Catalyzed C–H Activation/C–C Cross-Coupling Reactions: Versatility and Practicality

    PubMed Central

    Chen, Xiao; Engle, Keary M.; Wang, Dong-Hui; Yu, Jin-Quan

    2009-01-01

    In the past decade, palladium-catalyzed C–H activation/C–C bond forming reactions have emerged as promising new catalytic transformations; however, development in this field is still at an early stage compared to the state of the art in cross-coupling reactions using aryl and alkyl halides. This Review begins with a brief introduction of four extensively investigated modes of catalysis for forming C–C bonds from C–H bonds: Pd(II)/Pd(0), Pd(II)/Pd(IV), Pd(0)/Pd(II)/Pd(IV) and Pd(0)/Pd(II) catalysis. More detailed discussion is then directed towards the recent development of Pd(II)-catalyzed coupling of C–H bonds with organometallic reagents through a Pd(II)/Pd(0) catalytic cycle. Despite much progress made to date, improving the versatility and practicality of this new reaction remains a tremendous challenge. PMID:19557755

  20. Highly convergent, stereospecific synthesis of 11-cis-retinoids by metal-catalyzed cross-coupling reactions of (Z)-1-alkenylmetals.

    PubMed

    López, Susana; Montenegro, Javier; Saá, Carlos

    2007-12-01

    A stereospecific synthesis of 11-cis-retinoids has as its key step the hitherto unexplored palladium-catalyzed cross-coupling of trans-trienyl electrophiles and (1Z,3E)-penta-1,3-dienyl boronates (a Suzuki-Miyaura reaction) or stannanes (a Stille reaction). This highly convergent approach constitutes the first application of cis-organometallic moieties to the synthesis of 11-cis-retinoids and represents a general, straightforward route to the visual chromophore.

  1. Nickel-catalyzed decarboxylative cross-coupling of perfluorobenzoates with aryl halides and sulfonates.

    PubMed

    Sardzinski, Logan W; Wertjes, William C; Schnaith, Abigail M; Kalyani, Dipannita

    2015-03-01

    A Ni-catalyzed method for the coupling of perfluorobenzoates with aryl halides and pseudohalides is described. Aryl iodides, bromides, chlorides, triflates, and tosylates participate in these transformations to afford the products in good yields. Penta-, tetra-, and trifluorinated biaryl compounds are obtained using these newly developed Ni-catalyzed decarboxylative cross-coupling reactions.

  2. Cationic Pd(II)-catalyzed C–H activation/cross-coupling reactions at room temperature: synthetic and mechanistic studies

    PubMed Central

    Nishikata, Takashi; Abela, Alexander R; Huang, Shenlin

    2016-01-01

    Summary Cationic palladium(II) complexes have been found to be highly reactive towards aromatic C–H activation of arylureas at room temperature. A commercially available catalyst [Pd(MeCN)4](BF4)2 or a nitrile-free cationic palladium(II) complex generated in situ from the reaction of Pd(OAc)2 and HBF4, effectively catalyzes C–H activation/cross-coupling reactions between aryl iodides, arylboronic acids and acrylates under milder conditions than those previously reported. The nature of the directing group was found to be critical for achieving room temperature conditions, with the urea moiety the most effective in promoting facile coupling reactions at an ortho C–H position. This methodology has been utilized in a streamlined and efficient synthesis of boscalid, an agent produced on the kiloton scale annually and used to control a range of plant pathogens in broadacre and horticultural crops. Mechanistic investigations led to a proposed catalytic cycle involving three steps: (1) C–H activation to generate a cationic palladacycle; (2) reaction of the cationic palladacycle with an aryl iodide, arylboronic acid or acrylate, and (3) regeneration of the active cationic palladium catalyst. The reaction between a cationic palladium(II) complex and arylurea allowed the formation and isolation of the corresponding palladacycle intermediate, characterized by X-ray analysis. Roles of various additives in the stepwise process have also been studied. PMID:27340491

  3. Room-Temperature Palladium-Catalyzed Direct 2-Arylation of Benzoxazoles with Aryl and Heteroaryl Bromides†

    PubMed Central

    Gao, Feng; Kim, Byeong-Seon; Walsh, Patrick J.

    2014-01-01

    An efficient room-temperature palladium-catalyzed direct 2-arylation of benzoxazoles with aryl bromides is presented. The Pd(OAc)2/NiXantphos-based catalyst enables the introduction of various aryl and heteroaryl groups, via a deprotonative cross-coupling process (DCCP) in good to excellent yields (75–99%). PMID:25078988

  4. Advances in metal-catalyzed cross-coupling reactions of halogenated quinazolinones and their quinazoline derivatives.

    PubMed

    Mphahlele, Malose Jack; Maluleka, Marole Maria

    2014-10-29

    Halogenated quinazolinones and quinazolines are versatile synthetic intermediates for the metal-catalyzed carbon-carbon bond formation reactions such as the Kumada, Stille, Negishi, Sonogashira, Suzuki-Miyaura and Heck cross-coupling reactions or carbon-heteroatom bond formation via the Buchwald-Hartwig cross-coupling to yield novel polysubstituted derivatives. This review presents an overview of the application of these methods on halogenated quinazolin-4-ones and their quinazolines to generate novel polysubstituted derivatives.

  5. Secondary alkyl halides in transition-metal-catalyzed cross-coupling reactions.

    PubMed

    Rudolph, Alena; Lautens, Mark

    2009-01-01

    Enormous effort has gone into the development of metal-catalyzed cross-coupling reactions with alkyl halides as electrophilic coupling partners. Whereas a wide array of primary alkyl halides can now be used effectively in cross-coupling reactions, the synthetic potential of secondary alkyl halides is just beginning to be revealed. This Minireview summarizes selected examples of the use of secondary alkyl halides as electrophiles in cross-coupling reactions. Emphasis is placed on the transition metals employed, the mechanistic pathways involved, and implications in terms of the stereochemical outcome of reactions.

  6. 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

  7. 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

  8. Nickel-Catalyzed Cross-Coupling of Photoredox-Generated Radicals: Uncovering a General Manifold for Stereoconvergence in Nickel-Catalyzed Cross-Couplings

    PubMed Central

    2016-01-01

    The cross-coupling of sp3-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. PMID:25836634

  9. Synthesis of Aryldifluoroamides by Copper-Catalyzed Cross-Coupling.

    PubMed

    Arlow, Sophie I; Hartwig, John F

    2016-03-24

    A copper-catalyzed coupling of aryl, heteroaryl, and vinyl iodides with α-silyldifluoroamides is reported. The reaction forms α,α-difluoro-α-aryl amides from electron-rich, electron-poor, and sterically hindered aryl iodides in high yield and tolerates a variety of functional groups. The aryldifluoroamide products can be transformed further to provide access to a diverse array of difluoroalkylarenes, including compounds of potential biological interest. PMID:26929068

  10. Nickel-Catalyzed Negishi Cross-Coupling of Bromodifluoroacetamides.

    PubMed

    Tarui, Atsushi; Shinohara, Saori; Sato, Kazuyuki; Omote, Masaaki; Ando, Akira

    2016-03-01

    A nickel-catalyzed Negishi coupling of bromodifluoroacetamides with arylzinc reagents has been developed. This reaction allows access to difluoromethylated aromatic compounds containing a variety of aryl groups and amide moieties. Furthermore, highly effective transformation of the functionalized difluoromethyl group (-CF2CONR(1)R(2)) was realized via microwave-assisted reduction under mild conditions. The notable features of this strategy are its generality and its use of a low-cost nickel catalyst and ligand; thus, this reaction provides a facile method for applications in drug discovery and development. PMID:26910536

  11. Nickel 0-catalyzed cross-coupling of alkyl arenesulfonates with aryl Grignard reagents.

    PubMed

    Cho, Chul-Hee; Yun, Hee-Sung; Park, Kwangyong

    2003-04-18

    The nickel-catalyzed cross-coupling reactions of neopentyl arenesulfonates with arylmagnesium bromides, involving nucleophilic aromatic substitution of alkyloxysulfonyl groups by aryl nucleophiles, take place in high yields. Optimal efficiencies are obtained by adding 3 + 2 equiv of the Grignard reagent to a mixture of dppfNiCl(2) and the sulfonate in refluxing THF. Neopentyl arenesulfonates are useful sources of the electrophilic aryl groups in these transition metal-catalyzed cross-coupling reactions. Aryl sulfonates are inappropriate due to their ambident reactivity under the reaction conditions. This new cross-coupling reaction can be used for the creative elimination of alkyloxysulfonyl groups from aromatic compounds and for the preparation of unsymmetric terphenyls and oligophenyls.

  12. Nickel-Catalyzed Suzuki–Miyaura Cross-Coupling in a Green Alcohol Solvent for an Undergraduate Organic Chemistry Laboratory

    PubMed Central

    2015-01-01

    A modern undergraduate organic chemistry laboratory experiment involving the Suzuki–Miyaura coupling is reported. Although Suzuki–Miyaura couplings typically employ palladium catalysts in environmentally harmful solvents, this experiment features the use of inexpensive nickel catalysis, in addition to a “green” alcohol solvent. The experiment employs heterocyclic substrates, which are important pharmaceutical building blocks. Thus, this laboratory procedure exposes students to a variety of contemporary topics in organic chemistry, including transition metal-catalyzed cross-couplings, green chemistry, and the importance of heterocycles in drug discovery, none of which are well represented in typical undergraduate organic chemistry curricula. The experimental protocol uses commercially available reagents and is useful in both organic and inorganic instructional laboratories. PMID:25774064

  13. Towards Efficient and Wide-Scope Metal-Catalyzed Alkyl-Alkyl Cross-Coupling Reactions.

    PubMed

    Cárdenas

    1999-10-18

    The simplest organic fragment, C(sp(3))-C(sp(3)), is unfortunately the most difficult to prepare by metal-catalyzed cross-coupling reactions (shown schematically) in the presence of functional groups. Recent advances show, however, that alkane moieties can be built within functionalized molecules by a careful choice of catalysts and conditions.

  14. 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. PMID:25564373

  15. Copper-catalyzed C-N cross-coupling of sulfondiimines with boronic acids.

    PubMed

    Bohmann, Rebekka Anna; Bolm, Carsten

    2013-09-01

    The copper-catalyzed C-N cross-coupling of sulfondiimines with boronic acids has been developed. The reaction proceeds at room temperature in good to excellent yields and provides access to a variety of N,N'-disubstituted sulfondiimines, including N-(hetero)aryl sulfondiimines and the first reported N-alkenylated sulfondiimine. PMID:23937076

  16. Nickel-Catalyzed Asymmetric Kumada Cross-Coupling of Symmetric Cyclic Sulfates.

    PubMed

    Eno, Meredith S; Lu, Alexander; Morken, James P

    2016-06-29

    Nickel-catalyzed enantioselective cross-couplings between symmetric cyclic sulfates and aromatic Grignard reagents are described. These reactions are effective with a broad range of substituted cyclic sulfates and deliver products with asymmetric tertiary carbon centers. Mechanistic experiments point to a stereoinvertive SN2-like oxidative addition of a nickel complex to the electrophilic substrate. PMID:27276235

  17. Iron-Catalyzed Stereoselective Cross-Coupling Reactions of Stereodefined Enol Carbamates with Grignard Reagents.

    PubMed

    Rivera, Ana Cristina Parra; Still, Raymond; Frantz, Doug E

    2016-06-01

    A practical and highly stereoselective iron-catalyzed cross-coupling reaction of stereodefined enol carbamates and Grignard reagents to yield tri- and tetrasubstituted acrylates is reported. A facile method for the stereoselective generation of these enol carbamates has also been developed. PMID:27088754

  18. Palladium-catalyzed carbene migratory insertion using conjugated ene-yne-ketones as carbene precursors.

    PubMed

    Xia, Ying; Qu, Shuanglin; Xiao, Qing; Wang, Zhi-Xiang; Qu, Peiyuan; Chen, Li; Liu, Zhen; Tian, Leiming; Huang, Zhongxing; Zhang, Yan; Wang, Jianbo

    2013-09-11

    Palladium-catalyzed cross-coupling reactions between benzyl, aryl, or allyl bromides and conjugated ene-yne-ketones lead to the formation of 2-alkenyl-substituted furans. This novel coupling reaction involves oxidative addition, alkyne activation-cyclization, palladium carbene migratory insertion, β-hydride elimination, and catalyst regeneration. Palladium (2-furyl)carbene is proposed as the key intermediate, which is supported by DFT calculations. The palladium carbene character of the key intermediate is validated by three aspects, including bond lengths, Wiberg bond order indices, and molecular orbitals, by comparison to those reported for stable palladium carbene species. Computational studies also revealed that the rate-limiting step is ene-yne-ketone cyclization, which leads to the formation of the palladium (2-furyl)carbene, while the subsequent carbene migratory insertion is a facile process with a low energy barrier (<5 kcal/mol). PMID:23947689

  19. N-tosylhydrazones: versatile reagents for metal-catalyzed and metal-free cross-coupling reactions.

    PubMed

    Shao, Zhihui; Zhang, Hongbin

    2012-01-21

    Transition metal-catalyzed cross-coupling reactions have been established as one of the most powerful tools for the construction of C-C and C-X bonds. In this context, the development of novel metal-catalyzed cross-coupling processes that do not require stoichiometric organometallic reagents is particularly attractive. Recently, N-tosylhydrazones have emerged as a new type of versatile coupling partners for transition metal-catalyzed cross-coupling reactions as well as metal-free cross-coupling reactions, and have attracted increasing attention. This tutorial review summarizes recent important developments in this area with N-tosylhydrazones as versatile coupling partners.

  20. Palladium catalyzed hydrogenation of bio-oils and organic compounds

    DOEpatents

    Elliott, Douglas C.; Hu, Jianli; Hart, Todd R.; Neuenschwander, Gary G.

    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.

  1. 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.

  2. Fast and sequence-specific palladium-mediated cross-coupling reaction identified from phage display.

    PubMed

    Lim, Reyna K V; Li, Nan; Ramil, Carlo P; Lin, Qing

    2014-09-19

    Fast and specific bioorthogonal reactions are highly desirable because they provide efficient tracking of biomolecules that are present in low abundance and/or involved in fast dynamic process in living systems. Toward this end, classic strategy involves the optimization of substrate structures and reaction conditions in test tubes, testing their compatibility with biological systems, devising synthetic biology schemes to introduce the modified substrates into living cells or organisms, and finally validating the superior kinetics for enhanced capacity in tracking biomolecules in vivo--a lengthy process often mired by unexpected results. Here, we report a streamlined approach in which the "microenvironment" of a bioorthogonal chemical reporter is exploited directly in biological systems via phage-assisted interrogation of reactivity (PAIR) to optimize not only reaction kinetics but also specificity. Using the PAIR strategy, we identified a short alkyne-containing peptide sequence showing fast kinetics (k2=13,000±2000 M(-1) s(-1)) in a palladium-mediated cross-coupling reaction. Site-directed mutagenesis studies suggested that the residues surrounding the alkyne moiety facilitate the assembly of a key palladium-alkyne intermediate along the reaction pathway. When this peptide sequence was inserted into the extracellular domain of epidermal growth factor receptor (EGFR), this reactive sequence directed the specific labeling of EGFR in live mammalian cells. PMID:25025771

  3. Zinc-Catalyzed Dehydrogenative Cross-Coupling of Terminal Alkynes with Aldehydes: Access to Ynones.

    PubMed

    Tang, Shan; Zeng, Li; Liu, Yichang; Lei, Aiwen

    2015-12-21

    Because of the lack of redox ability, zinc has seldom been used as a catalyst in dehydrogenative cross-coupling reactions. Herein, a novel zinc-catalyzed dehydrogenative C(sp(2) )H/C(sp)H cross-coupling of terminal alkynes with aldehydes was developed, and provides a simple way to access ynones from readily available materials under mild reaction conditions. Good reaction selectivity can be achieved with a 1:1 ratio of terminal alkyne and aldehyde. Various terminal alkynes and aldehydes are suitable in this transformation. PMID:26564779

  4. Cross-coupling reaction with lithium methyltriolborate.

    PubMed

    Yamamoto, Yasunori; Ikizakura, Kazuya; Ito, Hajime; Miyaura, Norio

    2012-12-28

    We newly developed lithium methyltriolborate as an air-stable white solid that is convenient to handle. The good performance of this triolborate for metal-catalyzed bond-forming reactions was demonstrated in palladium-catalyzed cross-coupling reactions with haloarenes. Cross-coupling reaction of [MeB(OCH₂)₃CCH₃]Li with aryl halides occurred in the presence of Pd(OAc)₂/RuPhos complex in refluxing MeOH/H₂O and the absence of bases.

  5. 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

  6. Nickel-catalyzed dehydrogenative cross-coupling: direct transformation of aldehydes into esters and amides.

    PubMed

    Whittaker, Aaron M; Dong, Vy M

    2015-01-19

    By exploring a new mode of nickel-catalyzed cross-coupling, a method to directly transform both aromatic and aliphatic aldehydes into either esters or amides has been developed. 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. Mechanistic data that supports a catalytic cycle involving oxidative addition into the aldehyde C-H bond is also presented. PMID:25424967

  7. Nickel-Catalyzed Asymmetric Reductive Cross-Coupling between Heteroaryl Iodides and α-Chloronitriles.

    PubMed

    Kadunce, Nathaniel T; Reisman, Sarah E

    2015-08-26

    A Ni-catalyzed asymmetric reductive cross-coupling of heteroaryl iodides and α-chloronitriles has been developed. This method furnishes enantioenriched α,α-disubstituted nitriles from simple organohalide building blocks. The reaction tolerates a variety of heterocyclic coupling partners, including pyridines, pyrimidines, quinolines, thiophenes, and piperidines. The reaction proceeds under mild conditions at room temperature and precludes the need to pregenerate organometallic nucleophiles.

  8. New insights into the mechanism of iron-catalyzed cross-coupling reactions.

    PubMed

    Bekhradnia, Ahmadreza; Norrby, Per-Ola

    2015-03-01

    The mechanism of the iron-catalyzed cross-coupling of alkyl halides with aryl Grignard reagents is studied by a combination of GC monitoring and DFT calculation. Herein, we investigate two possible reaction pathways, the regular oxidative addition (OA) pathway and the atom transfer (AT) pathway that might occur in the rate-limiting step. The computational studies revealed that the AT pathway requires less energy than the regular OA pathway. PMID:25649755

  9. Fast and Sequence-Specific Palladium-Mediated Cross-Coupling Reaction Identified from Phage Display

    PubMed Central

    2015-01-01

    Fast and specific bioorthogonal reactions are highly desirable because they provide efficient tracking of biomolecules that are present in low abundance and/or involved in fast dynamic process in living systems. Toward this end, classic strategy involves the optimization of substrate structures and reaction conditions in test tubes, testing their compatibility with biological systems, devising synthetic biology schemes to introduce the modified substrates into living cells or organisms, and finally validating the superior kinetics for enhanced capacity in tracking biomolecules in vivo—a lengthy process often mired by unexpected results. Here, we report a streamlined approach in which the “microenvironment” of a bioorthogonal chemical reporter is exploited directly in biological systems via phage-assisted interrogation of reactivity (PAIR) to optimize not only reaction kinetics but also specificity. Using the PAIR strategy, we identified a short alkyne-containing peptide sequence showing fast kinetics (k2 = 13 000 ± 2000 M–1 s–1) in a palladium-mediated cross-coupling reaction. Site-directed mutagenesis studies suggested that the residues surrounding the alkyne moiety facilitate the assembly of a key palladium–alkyne intermediate along the reaction pathway. When this peptide sequence was inserted into the extracellular domain of epidermal growth factor receptor (EGFR), this reactive sequence directed the specific labeling of EGFR in live mammalian cells. PMID:25025771

  10. Organogold reactivity with palladium, nickel, and rhodium: transmetalation, cross-coupling, and dual catalysis.

    PubMed

    Hirner, Joshua J; Shi, Yili; Blum, Suzanne A

    2011-08-16

    Using two transition metals to simultaneously catalyze a reaction can offer distinct opportunities for reactivity and selectivity when compared to using single-metal catalyst systems. Creating dual transition metal catalytic systems is complicated, however, by challenges in predicting compatible reactivities and designing turnover pathways for both metals. In this Account, we describe our development of dual-metal catalysis reactions involving gold and a second transition metal. The unique rearrangement intermediates accessible through gold-only catalysis, which exploits the soft Lewis acidity of Au(I), make gold an attractive partner for dual-metal catalysis reactions. Because of the complexity of achieving simultaneous turnover of two catalysts and predicting compatibilities, our approach has been to first gain a fundamental understanding of the reactivity of the two metals with each other, both in stoichiometric and monocatalyzed reactions. To this end, we have investigated the combined reactivity of organogold compounds with palladium, nickel, and rhodium. We narrate the intricacies of turning over two catalysts simultaneously and thereby illuminate the valuable role of fundamental studies in identifying the optimal conditions to promote desirable two-metal reactivity and compatibility. Transmetalation, redox reactivity, and new mechanisms for dual-metal catalytic turnover were probed from this standpoint. We have applied the knowledge gained through these studies to the development of reactions that are dual-catalyzed by gold and palladium, as well as nickel- and rhodium-catalyzed reactions of organogold compounds. More broadly, these new reactions expand the reactivity available to catalytic organogold intermediates via trapping and functionalization reactions with other transition metals. Our investigations reveal strategies useful for designing dual-metal reactions with gold. First, the versatility of gold as a transmetalation partner suggests that many

  11. 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)

  12. Copper-assisted palladium(II)-catalyzed direct arylation of cyclic enaminones with arylboronic acids.

    PubMed

    Kim, Yong Wook; Niphakis, Micah J; Georg, Gunda I

    2012-11-01

    Described herein is a palladium(II)-catalyzed direct arylation of cyclic enaminones with arylboronic acids. The versatility of this method is that both electron-rich and electron-poor boronic acids can be coupled in high yields. A mixture of two Cu(II) additives was crucial for efficient cross-coupling. The role of each Cu(II) reagent appears to be distinct and complementary serving to assist catalyst reoxidation and transmetalation through a putative arylcopper intermediate. PMID:23088256

  13. 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. PMID:25470669

  14. Alkene synthesis through transition metal-catalyzed cross-coupling of N-tosylhydrazones.

    PubMed

    Zhang, Yan; Wang, Jianbo

    2012-01-01

    In this chapter, alkene synthesis based on the reaction of N-tosylhydrazones is described. The reactivity of tosylhydrazones is determined by either the acidity of α-proton and hydrazone proton or the electropositivity of the carbon of C=N bond. This leads to diverse reactivities and a series of N-tosylhydrazone-based olefination methodologies. Both non-catalytic and transition metal-catalyzed olefinations from N-tosylhydrazones are introduced in this chapter. Most of the transition metal-catalyzed reactions proceed via metal carbene transformations. The synthesis of alkenes through Pd-catalyzed cross-coupling reactions of N-tosylhydrazones is particularly attractive and will be discussed in detail.

  15. Silver-Catalyzed Cross-Coupling of Isocyanides and Active Methylene Compounds by a Radical Process.

    PubMed

    Liu, Jianquan; Liu, Zhenhua; Liao, Peiqiu; Zhang, Lin; Tu, Tao; Bi, Xihe

    2015-09-01

    Isocyanides are versatile building blocks, and have been extensively exploited in C-H functionalization reactions. However, transition-metal-catalyzed direct C-H functionalization reactions with isocyanides suffer from over-insertion of isocyanides. Reported herein is a radical coupling/isomerization strategy for the cross-coupling of isocyanides with active methylene compounds through silver-catalysis. The method solves the over-insertion issue and affords a variety of otherwise difficult to synthesize β-aminoenones and tricarbonylmethanes under base- and ligand-free conditions. This report presents a new fundamental C-C bond-forming reaction of two basic chemicals.

  16. On the radical nature of iron-catalyzed cross-coupling reactions.

    PubMed

    Hedström, Anna; Izakian, Zakieh; Vreto, Irma; Wallentin, Carl-Johan; Norrby, Per-Ola

    2015-04-01

    The radical nature of iron-catalyzed cross-coupling between Grignard reagents and alkyl halides has been studied by using a combination of competitive kinetic experiments and DFT calculations. In contrast to the corresponding coupling with aryl halides, which commences through a classical two-electron oxidative addition/reductive elimination sequence, the presented data suggest that alkyl halides react through an atom-transfer-initiated radical pathway. Furthermore, a general iodine-based quenching methodology was developed to enable the determination of highly accurate concentrations of Grignard reagents, a capability that facilitates and increases the information output of kinetic investigations based on these substrates. PMID:25703202

  17. Computational study of gold-catalyzed homo- and cross-coupling reactions.

    PubMed

    Nieto Faza, Olalla; Silva López, Carlos

    2013-05-17

    The role of gold as the organizing metal in homo- and cross-coupling reactions is explored in this paper combining DFT calculations with QTAIM, NBO, and the energetic span model analysis. For the gold(III) complex 7, a key intermediate in the experimental oxidative coupling scheme by Zhang et al., we describe the mechanisms corresponding to a cross-coupling after transmetalation with boron compounds and to a homocoupling after transmetalation with the original gold(I) complex 6, a new example of dual role of this metal in homogeneous catalysis. We predict for the first path a two-step transmetalation with a low energy rate-limiting step characterized by a four-center transition structure, where fluorine plays an essential role, followed by a reductive elimination where the C-C bond formation is coupled to the departure of fluorine from the gold center. The homocoupling path follows a similar mechanism, with a two-step transmetalation with interesting changes in bonding around the Au(I) center and a rate-limiting reductive elimination. Our findings on the competition between mechanisms, and the effect of ligands and solvent, agree with the experimental results and provide new insights into the mechanism of gold-catalyzed cross-coupling reactions. PMID:23597253

  18. Recent advances of transition-metal catalyzed radical oxidative cross-couplings.

    PubMed

    Liu, Chao; Liu, Dong; Lei, Aiwen

    2014-12-16

    CONSPECTUS: Oxidative cross-coupling reactions between two nucleophiles are a powerful synthetic strategy to synthesize various kinds of functional molecules. Along with the development of transition-metal-catalyzed oxidative cross-coupling reactions, chemists are applying more and more first-row transition metal salts (Fe, Co, etc.) as catalysts. Since first-row transition metals often can go through multiple chemical valence changes, those oxidative cross-couplings can involve single electron transfer processes. In the meantime, chemists have developed diverse mechanistic hypotheses of these types of reactions. However, none of these hypotheses have led to conclusive reaction pathways until now. From studying both our own work and that of others in this field, we believe that radical oxidative cross-coupling reactions can be classified into four models based on the final bond formations. In this Account, we categorize and summarize these models. In model I, one of the starting nucleophiles initially loses one electron to generate its corresponding radical under oxidative conditions. Then, bond formations between this radical and another nucleophile create a new radical, [Nu(1)-Nu(2)](•), followed by a further radical oxidation step to generate the cross-coupling product. The radical oxidative alkenylation with olefin, radical oxidative arylative-annulation, and radical oxidative amidation are examples of this model. In model II, one of the starting nucleophiles loses its two electrons via two steps of single-electron-transfer to generate an electrophilic intermediate, followed by a direct bond formation with the other nucleophile. For example, the oxidative C-O coupling of benzylic sp(3) C-H bonds with carboxylic acids and oxidative C-N coupling of aldehydes with amides are members of this model group. For model III, both nucleophiles are oxidized to their corresponding radicals. Then, the radicals combine to form the final coupling product. The dioxygen

  19. 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. PMID:21879127

  20. Toluene derivatives as simple coupling precursors for cascade palladium-catalyzed oxidative C-H bond acylation of acetanilides.

    PubMed

    Wu, Yinuo; Choy, Pui Ying; Mao, Fei; Kwong, Fuk Yee

    2013-01-25

    A palladium-catalyzed cascade cross-coupling of acetanilide and toluene for the synthesis of ortho-acylacetanilide is described. Toluene derivatives can act as effective acyl precursors (upon sp(3)-C-H bond oxidation by a Pd/TBHP system) in the oxidative coupling between two C-H bonds. This dehydrogenative Pd-catalyzed ortho-acylation proceeds under mild reaction conditions. PMID:23230572

  1. Configurationally Stable, Enantioenriched Organometallic Nucleophiles in Stereospecific Pd-Catalyzed Cross-Coupling Reactions: An Alternative Approach to Asymmetric Synthesis

    PubMed Central

    Wang, Chao-Yuan; Derosaa, Joseph

    2015-01-01

    Several research groups have recently developed methods to employ configurationally stable, enantioenriched organometallic nucleophiles in stereospecific Pd-catalyzed cross-coupling reactions. By establishing the absolute configuration of a chiral alkyltin or alkylboron nucleophile prior to its use in cross-coupling reactions, new stereogenic centers may be rapidly and reliably generated with preservation of the known initial stereochemistry. While this area of research is still in its infancy, such stereospecific cross-coupling reactions may emerge as simple, general methods to access diverse, optically active products from common enantioenriched organometallic building blocks. This minireview highlights recent progress towards the development of general, stereospecific Pd-catalyzed cross-coupling reactions using configurationally stable organometallic nucleophiles. PMID:26388985

  2. Stereospecific Nickel-Catalyzed Cross-Coupling Reactions of Benzylic Ethers with Isotopically-Labeled Grignard Reagents

    PubMed Central

    2015-01-01

    In this manuscript we highlight the potential of stereospecific nickel-catalyzed cross-coupling reactions for applications in the pharmaceutical industry. Using an inexpensive and sustainable nickel catalyst, we report a gram-scale Kumada cross-coupling reaction. Reactions are highly stereospecific and proceed with inversion at the benzylic position. We also expand the scope of our reaction to incorporate isotopically labeled substituents. PMID:27458328

  3. Cobalt-Catalyzed Oxidative C-H/C-H Cross-Coupling between Two Heteroarenes.

    PubMed

    Tan, Guangying; He, Shuang; Huang, Xiaolei; Liao, Xingrong; Cheng, Yangyang; You, Jingsong

    2016-08-22

    The first example of cobalt-catalyzed oxidative C-H/C-H cross-coupling between two heteroarenes is reported, which exhibits a broad substrate scope and a high tolerance level for sensitive functional groups. When the amount of Co(OAc)2 ⋅4 H2 O is reduced from 6.0 to 0.5 mol %, an excellent yield is still obtained at an elevated temperature with a prolonged reaction time. The method can be extended to the reaction between an arene and a heteroarene. It is worth noting that the Ag2 CO3 oxidant is renewable. Preliminary mechanistic studies by radical trapping experiments, hydrogen/deuterium exchange experiments, kinetic isotope effect, electron paramagnetic resonance (EPR), and high resolution mass spectrometry (HRMS) suggest that a single electron transfer (SET) pathway is operative, which is distinctly different from the dual C-H bond activation pathway that the well-described oxidative C-H/C-H cross-coupling reactions between two heteroarenes typically undergo. PMID:27460406

  4. Cobalt-Catalyzed Oxidative C-H/C-H Cross-Coupling between Two Heteroarenes.

    PubMed

    Tan, Guangying; He, Shuang; Huang, Xiaolei; Liao, Xingrong; Cheng, Yangyang; You, Jingsong

    2016-08-22

    The first example of cobalt-catalyzed oxidative C-H/C-H cross-coupling between two heteroarenes is reported, which exhibits a broad substrate scope and a high tolerance level for sensitive functional groups. When the amount of Co(OAc)2 ⋅4 H2 O is reduced from 6.0 to 0.5 mol %, an excellent yield is still obtained at an elevated temperature with a prolonged reaction time. The method can be extended to the reaction between an arene and a heteroarene. It is worth noting that the Ag2 CO3 oxidant is renewable. Preliminary mechanistic studies by radical trapping experiments, hydrogen/deuterium exchange experiments, kinetic isotope effect, electron paramagnetic resonance (EPR), and high resolution mass spectrometry (HRMS) suggest that a single electron transfer (SET) pathway is operative, which is distinctly different from the dual C-H bond activation pathway that the well-described oxidative C-H/C-H cross-coupling reactions between two heteroarenes typically undergo.

  5. Melamine and melamine-formaldehyde polymers as ligands for palladium and application to Suzuki-Miyaura cross-coupling reactions in sustainable solvents.

    PubMed

    Edwards, Grant A; Trafford, Mitchell A; Hamilton, Alaina E; Buxton, Audrey M; Bardeaux, Matthew C; Chalker, Justin M

    2014-03-01

    The Suzuki-Miyaura cross-coupling reaction is a foundation stone of modern organic synthesis, as evidenced by its widespread use in the preparation of pharmaceuticals, agrochemicals, polymers, and other functional materials. With the prevalence of this venerable reaction in industrial synthesis, it is prudent to ensure its application adheres to the tenets of green chemistry. The introduction of cross-coupling catalysts that are active in sustainable solvents is therefore an important endeavor. In this report, a melamine-palladium complex is introduced as a versatile catalyst for the Suzuki-Miyaura cross-coupling reaction. This catalyst is soluble and active in both water and the renewable organic solvent ethyl lactate. The melamine-palladium catalyst can also be cross-linked by reaction with formaldehyde to generate an insoluble polymeric catalyst that can be recovered after the cross-coupling. The melamine-palladium system is inexpensive, easy to handle, bench-stable, and effective in catalysis in the presence of a variety of impurities (high cross-coupling yields were obtained in reactions run in unfiltered river water to illustrate this final point). Additionally, investigations reported herein revealed an intriguing relationship between catalytic efficiency and the base employed in the cross-coupling reaction. Implications for the mechanism of transmetalation in aqueous Suzuki-Miyaura cross-coupling reaction are discussed.

  6. More than bystanders: the effect of olefins on transition-metal-catalyzed cross-coupling reactions.

    PubMed

    Johnson, Jeffrey B; Rovis, Tomislav

    2008-01-01

    Olefins and alkynes are ubiquitous in transition-metal catalysis, whether introduced by the substrate, the catalyst, or as an additive. Whereas the impact of metals and ligands is relatively well understood, the effects of olefins in these reactions are generally underappreciated, even though numerous examples of olefins influencing the outcome of a reaction, through increased activity, stability, or selectivity, have been reported. This Review provides an overview of the interaction of olefins with transition metals and documents examples of olefins influencing the outcome of catalytic reactions, in particular cross-coupling reactions. It should thus provide a basis for the improved understanding and further utilization of olefin and alkyne effects in transition-metal-catalyzed reactions.

  7. Mixed-ligand catalysts: a powerful tool in transition-metal- catalyzed cross-coupling reactions.

    PubMed

    Fan, Yuting; Cong, Mei; Peng, Ling

    2014-03-01

    Transition-metal-catalyzed cross-coupling reactions have fundamentally revolutionized organic synthesis, empowering the otherwise difficult to achieve products with rapid and convenient accesses alongside excellent yields. Within these reactions, ligands often play a critical role in specifically and effectively advocating the corresponding catalysis. Consequently, a myriad of ligands have been created and applied to make a fine tuning of electronic and steric effect of catalysts, remarkably promoting catalytic efficiency and applicability. The "mixed-ligand" concept has recently emerged; by combining and capitalizing on the superiority of each individual ligand already available, an expedient way can be achieved to reach a larger extent of catalytic diversity and efficacy. Given the availability of a wealth of ligands, it is reasonable to have great expectations for the original application of mixed-ligand catalytic systems and their important value in organic synthesis.

  8. Theoretical study on the mechanism of Ni-catalyzed alkyl-alkyl Suzuki cross-coupling.

    PubMed

    Li, Zhe; Jiang, Yuan-Ye; Fu, Yao

    2012-04-01

    Ni-catalyzed cross-coupling of unactivated secondary alkyl halides with alkylboranes provides an efficient way to construct alkyl-alkyl bonds. The mechanism of this reaction with the Ni/L1 (L1=trans-N,N'-dimethyl-1,2-cyclohexanediamine) system was examined for the first time by using theoretical calculations. The feasible mechanism was found to involve a Ni(I)-Ni(III) catalytic cycle with three main steps: transmetalation of [Ni(I)(L1)X] (X=Cl, Br) with 9-borabicyclo[3.3.1]nonane (9-BBN)R(1) to produce [Ni(I)(L1)(R(1))], oxidative addition of R(2) X with [Ni(I)(L1)(R(1))] to produce [Ni(III)(L1)(R(1))(R(2))X] through a radical pathway, and C-C reductive elimination to generate the product and [Ni(I)(L1)X]. The transmetalation step is rate-determining for both primary and secondary alkyl bromides. KOiBu decreases the activation barrier of the transmetalation step by forming a potassium alkyl boronate salt with alkyl borane. Tertiary alkyl halides are not reactive because the activation barrier of reductive elimination is too high (+34.7 kcal mol(-1)). On the other hand, the cross-coupling of alkyl chlorides can be catalyzed by Ni/L2 (L2=trans-N,N'-dimethyl-1,2-diphenylethane-1,2-diamine) because the activation barrier of transmetalation with L2 is lower than that with L1. Importantly, the Ni(0)-Ni(II) catalytic cycle is not favored in the present systems because reductive elimination from both singlet and triplet [Ni(II)(L1)(R(1))(R(2))] is very difficult.

  9. Synthesis of marine polyacetylenes callyberynes A-C by transition-metal-catalyzed cross-coupling reactions to sp centers.

    PubMed

    López, Susana; Fernandez-Trillo, Francisco; Midón, Pilar; Castedo, Luis; Saa, Carlos

    2006-03-31

    Efficient total syntheses of the sponge-derived hydrocarbon polyacetylenes callyberynes A-C have been achieved using metal-catalyzed cross-coupling reactions of highly unsaturated 1,3-diyne fragments as the key steps, namely: Cadiot-Chodkiewicz reaction under Alami's optimized conditions (sp-sp), sequential Sonogashira reaction of a cis,cis-divinyl dihalide (sp2-sp), and Kumada-Corriu reaction of an unactivated alkyl iodide (sp3-sp). This last approach constitutes the first application of a metal-catalyzed sp3-sp Kumada-Corriu cross-coupling reaction to the synthesis of a natural product.

  10. 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

  11. 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

  12. Stereospecific Nickel-Catalyzed Cross-Coupling Reactions of Benzylic Ethers and Esters

    PubMed Central

    2015-01-01

    Conspectus 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

  13. 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. PMID:25955413

  14. An efficient copper-catalyzed cross-coupling reaction of alkyl-triflates with alkyl-Grignard reagents

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A highly efficient method for the formation of C-C covalent bonds by cross-coupling reaction between alkyl-triflates and alkyl-Grignard reagents catalyzed by copper catalyst, Li2CuCl4, is described. The reaction works with most primary triflates in diethyl ether at low temperature within 0.5-3 h an...

  15. Selective Nickel- and Manganese-Catalyzed Decarboxylative Cross Coupling of Some α,β-Unsaturated Carboxylic Acids with Cyclic Ethers

    PubMed Central

    Zhang, Jia-Xiang; Wang, Yan-Jing; Zhang, Wei; Wang, Nai-Xing; Bai, Cui-Bing; Xing, Ya-Lan; Li, Yi-He; Wen, Jia-Long

    2014-01-01

    A nickel- and manganese-catalyzed decarboxylative cross coupling of α, β-unsaturated carboxylic acids with cyclic ethers such as tetrahydrofuran and 1, 4-dioxane was developed. Oxyalkylation was achieved when nickel acetate was used as catalyst, while manganese acetate promoted the reaction of alkenylation. PMID:25502282

  16. New efficient ligand for sub-mol % copper-catalyzed C-N cross-coupling reactions running under air.

    PubMed

    Larsson, Per-Fredrik; Astvik, Peter; Norrby, Per-Ola

    2012-01-01

    A new efficient ligand, N,N''-dimethyldiethylene triamine (DMDETA), has been synthesized and evaluated for sub-mol % copper-catalyzed C-N cross-coupling reactions. The efficiency of the ligand was determined by kinetic methods. DMDETA proved to display efficiency similar to DMEDA and, in addition, the resulting catalyst was tolerant to air. PMID:23209530

  17. New efficient ligand for sub-mol % copper-catalyzed C–N cross-coupling reactions running under air

    PubMed Central

    Larsson, Per-Fredrik; Astvik, Peter

    2012-01-01

    Summary A new efficient ligand, N,N’’-dimethyldiethylene triamine (DMDETA), has been synthesized and evaluated for sub-mol % copper-catalyzed C–N cross-coupling reactions. The efficiency of the ligand was determined by kinetic methods. DMDETA proved to display efficiency similar to DMEDA and, in addition, the resulting catalyst was tolerant to air. PMID:23209530

  18. Nickel-Catalyzed Alkylative Cross-Coupling of Anisoles with Grignard Reagents via C-O Bond Activation.

    PubMed

    Tobisu, Mamoru; Takahira, Tsuyoshi; Morioka, Toshifumi; Chatani, Naoto

    2016-06-01

    We report nickel-catalyzed cross-coupling of methoxyarenes with alkylmagnesium halides, in which a methoxy group is eliminated. A wide range of alkyl groups, including those bearing β-hydrogens, can be introduced directly at the ipso position of anisole derivatives. We demonstrate that the robustness of a methoxy group allows this alkylation protocol to be used to synthesize elaborate molecules by combining it with traditional cross-coupling reactions or oxidative transformation. The success of this method is dependent on the use of alkylmagnesium iodides, but not chlorides or bromides, which highlights the importance of the halide used in developing catalytic reactions using Grignard reagents. PMID:27193503

  19. Rapid formation of triarylphosphines by microwave-assisted transition metal-catalyzed C-p cross-coupling reactions.

    PubMed

    Stadler, Alexander; Kappe, C Oliver

    2002-10-01

    Rapid, direct transition metal-catalyzed C-P(III) cross-coupling reactions were performed by microwave dielectric heating, employing diphenylphosphine and aryl halides/triflates as substrates. Depending on the specific aryl halide/triflate precursor, the highest yields were obtained utilizing heterogeneous or homogeneous Pd or Ni catalysts in DMF or NMP in the presence of KOAc or DABCO as a base. [reaction: see text

  20. Copper-catalyzed reductive cross-coupling of nonactivated alkyl tosylates and mesylates with alkyl and aryl bromides.

    PubMed

    Liu, Jing-Hui; Yang, Chu-Ting; Lu, Xiao-Yu; Zhang, Zhen-Qi; Xu, Ling; Cui, Mian; Lu, Xi; Xiao, Bin; Fu, Yao; Liu, Lei

    2014-11-17

    A copper-catalyzed reductive cross-coupling reaction of nonactivated alkyl tosylates and mesylates with alkyl and aryl bromides was developed. It provides a practical method for efficient and cost-effective construction of aryl-alkyl and alkyl-alkyl CC bonds with stereocontrol from readily available substrates. When used in an intramolecular fashion, the reaction enables convenient access to various substituted carbo- or heterocycles, such as 2,3-dihydrobenzofuran and benzochromene derivatives.

  1. Selective formation of secondary amides via the copper-catalyzed cross-coupling of alkylboronic acids with primary amides.

    PubMed

    Rossi, Steven A; Shimkin, Kirk W; Xu, Qun; Mori-Quiroz, Luis M; Watson, Donald A

    2013-05-01

    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 monoalkylation of amides. PMID:23611591

  2. CuBr catalyzed C-N cross coupling reaction of purines and diaryliodonium salts to 9-arylpurines.

    PubMed

    Niu, Hong-Ying; Xia, Chao; Qu, Gui-Rong; Zhang, Qian; Jiang, Yi; Mao, Run-Ze; Li, De-Yang; Guo, Hai-Ming

    2011-07-21

    CuBr was found to be an efficient catalyst for the C-N cross coupling reaction of purine and diaryliodonium salts. 9-Arylpurines were synthesized in excellent yields with short reaction times (2.5 h). The method represents an alternative to the synthesis of 9-arylpurines via Cu(II) catalyzed C-N coupling reaction with arylboronic acids as arylating agents. PMID:21660365

  3. Organo-Iodine(III)-Catalyzed Oxidative Phenol-Arene and Phenol-Phenol Cross-Coupling Reaction.

    PubMed

    Morimoto, Koji; Sakamoto, Kazuma; Ohshika, Takao; Dohi, Toshifumi; Kita, Yasuyuki

    2016-03-01

    The direct oxidative coupling reaction has been an attractive tool for environmentally benign chemistry. Reported herein is that the hypervalent iodine catalyzed oxidative metal-free cross-coupling reaction of phenols can be achieved using Oxone as a terminal oxidant in 1,1,1,3,3,3-hexafluoropropan-2-ol (HFIP). This method features a high efficiency and regioselectivity, as well as functional-group tolerance under very mild reaction conditions without using metal catalysts. PMID:26879796

  4. Iron-Catalyzed Cross-Coupling of Unactivated, Secondary Alkyl Thio Ethers and Sulfones with Aryl Grignard Reagents

    PubMed Central

    Denmark, Scott E.; Cresswell, Alexander J.

    2013-01-01

    The first systematic investigation of unactivated aliphatic sulfur compounds as electrophiles in transition metal-catalyzed cross-coupling are described. Initial studies focused on discerning the structural and electronic features of the organosulfur substrate which enable the challenging oxidative addition to the C(sp3)–S bond. Through extensive optimization efforts, an Fe(acac)3-catalyzed cross-coupling of unactivated alkyl aryl thio ethers with aryl Grignard reagents was realized, in which a nitrogen “directing group” on the S-aryl moiety of the thio ether served a critical role in facilitating the oxidative addition step. In addition, alkyl phenyl sulfones were found to be effective electrophiles in the Fe(acac)3-catalyzed cross-coupling with aryl Grignard reagents. For the latter class of electrophile, a thorough assessment of the various reaction parameters revealed a dramatic enhancement in reaction efficiency with an excess of TMEDA (8.0 equiv). The optimized reaction protocol was used to evaluate the scope of the method with respect to both the organomagnesium nucleophile and sulfone electrophile. PMID:24256193

  5. 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. PMID:25899175

  6. Total Synthesis of Macrocarpines D and E via an Enolate-Driven Copper-Mediated Cross-Coupling Process: Replacement of Catalytic Palladium with Copper Iodide.

    PubMed

    Rahman, M Toufiqur; Deschamps, Jeffrey R; Imler, Gregory H; Schwabacher, Alan W; Cook, James M

    2016-09-01

    An enolate driven copper-mediated cross-coupling process enabled cheaper and greener access to the key pentacyclic intermediates required for the enantiospecific total synthesis of a number of C-19 methyl substituted sarpagine/macroline indole alkaloids. Replacement of palladium (60-68%) with copper iodide (82-89%) resulted in much higher yields. The formation of an unusual 7-membered cross-coupling product was completely inhibited by using TEMPO as a radical scavenger. Further functionalization led to the first enantiospecific total synthesis of macrocarpines D and E. PMID:27526647

  7. Synthesis of α,α-difluoromethylene alkynes by palladium-catalyzed gem-difluoropropargylation of aryl and alkenyl boron reagents.

    PubMed

    Yu, Yan-Bo; He, Guo-Zhen; Zhang, Xingang

    2014-09-22

    gem-Difluoropropargyl bromides are versatile intermediates in organic synthesis, but have rarely been employed in transition-metal-catalyzed cross-coupling reactions. The first palladium-catalyzed gem-difluoropropargylation of organoboron reagents with gem-difluoropropargyl bromides is now reported. The reaction proceeds under mild reaction conditions with high regioselectivity; it features a broad substrate scope and excellent functional-group compatibility and thus provides an attractive approach for the synthesis of complex fluorinated molecules, in particular for drug discovery and development.

  8. Palladium-Catalyzed Direct Cyclopropylation of Heterocycles.

    PubMed

    Wu, Xiaojin; Lei, Chuanhu; Yue, Guizhou; Zhou, Jianrong Steve

    2015-08-10

    Many 1,3-azoles and thiophenes are directly cyclopropylated in the presence of a simple palladium catalyst. The relative configuration on the three-membered rings is retained in the products. Thus, the cyclopropyl-halide bond undergoes concerted oxidative addition to palladium(0) and cyclopropyl radicals are not involved in the productive pathway.

  9. Heterocycle Formation via Palladium-Catalyzed C–H Functionalization

    PubMed Central

    Mei, Tian-Sheng; Kou, Lei; Ma, Sandy; Engle, Keary M.; Yu, Jin-Quan

    2016-01-01

    Heterocyclic compounds are ubiquitous in natural products, pharmaceuticals, and agrochemicals. Therefore, the design of novel protocols to construct heterocycles more efficiently is a major area of focus in the organic chemistry. In the past several years, cyclization reactions based upon palladium-catalyzed C–H activation have received substantial attention due to their capacity for expediting heterocycle synthesis. This review discusses strategies for heterocycle synthesis via palladium-catalyzed C–H bond activation and highlights recent examples from the literature. PMID:27397938

  10. Copper nanoparticle-catalyzed cross-coupling of alkyl halides with Grignard reagents.

    PubMed

    Kim, Ju Hyun; Chung, Young Keun

    2013-12-01

    A cross-coupling reaction between alkyl bromides and chlorides and various Grignard reagents was carried out in the presence of commercially available copper or copper oxide nanoparticles as a catalyst and an alkyne additive. The catalytic system shows high activity, a broad scope, and good functional group tolerance. PMID:24146018

  11. Efficient palladium-catalyzed aminocarbonylation of aryl iodides using palladium nanoparticles dispersed on siliceous mesocellular foam.

    PubMed

    Tinnis, Fredrik; Verho, Oscar; Gustafson, Karl P J; Tai, Cheuk-Wai; Bäckvall, Jan-E; Adolfsson, Hans

    2014-05-12

    A highly dispersed nanopalladium catalyst supported on mesocellular foam (MCF), was successfully used in the heterogeneous catalysis of aminocarbonylation reactions. During the preliminary evaluation of this catalyst it was discovered that the supported palladium nanoparticles exhibited a "release and catch" effect, meaning that a minor amount of the heterogeneous palladium became soluble and catalyzed the reaction, after which it re-deposited onto the support.

  12. Effects of Molecular Oxygen, Solvent, and Light on Iridium-Photoredox/Nickel Dual-Catalyzed Cross-Coupling Reactions.

    PubMed

    Oderinde, Martins S; Varela-Alvarez, Adrian; Aquila, Brian; Robbins, Daniel W; Johannes, Jeffrey W

    2015-08-01

    In order to achieve reproducibility during iridium-photoredox and nickel dual-catalyzed sp(3)-sp(2) carbon-carbon bond-forming reactions, we investigated the role that molecular oxygen (O2), solvent and light-source (CF lamp or blue LED) play in a variety of Ir-photoredox mediated transformations. The presence of O2 was discovered to be important for catalyst activation when air-stable Ni(II) precatalysts were used in DMF under CF lamp irradiation; however, O2 was not required for catalysis when conducted with Ni(COD)2 in the same reaction system. O2 is believed to promote rapid reduction of the Ni(II) precatalyst by Ir(II) to Ni(0). In addition to O2, the effects that solvent and light-source have on the dual-catalyzed decarboxylative cross-coupling reactions will be discussed. These findings have enabled us to develop a more robust dual-catalyzed decarboxylative cross-coupling protocol.

  13. Palladium-catalyzed C–N and C–O bond formation of N-substituted 4-bromo-7-azaindoles with amides, amines, amino acid esters and phenols

    PubMed Central

    Surasani, Rajendra; Rao, A V Dhanunjaya; Chandrasekhar, K B

    2012-01-01

    Summary Simple and efficient procedures for palladium-catalyzed cross-coupling reactions of N-substituted 4-bromo-7-azaindole (1H-pyrrole[2,3-b]pyridine), with amides, amines, amino acid esters and phenols through C–N and C–O bond formation have been developed. The C–N cross-coupling reaction of amides, amines and amino acid esters takes place rapidly by using the combination of Xantphos, Cs2CO3, dioxane and palladium catalyst precursors Pd(OAc)2/Pd2(dba)3. The combination of Pd(OAc)2, Xantphos, K2CO3 and dioxane was found to be crucial for the C–O cross-coupling reaction. This is the first report on coupling of amides, amino acid esters and phenols with N-protected 4-bromo-7-azaindole derivatives. PMID:23209536

  14. Photoredox Catalysis Unlocks Single-Electron Elementary Steps in Transition Metal Catalyzed Cross-Coupling

    PubMed Central

    2016-01-01

    Since initial reports, cross-coupling technologies employing photoredox catalysts to access novel reactivity have developed with increasing pace. In this Outlook, prominent examples from the recent literature are organized on the basis of the elementary transformation enabled by photoredox catalysis and are discussed in the context of relevant historical precedent in stoichiometric organometallic chemistry. This treatment allows mechanistic similarities inherent to odd-electron transition metal reactivity to be generalized to a set of lessons for future reaction development. PMID:27280163

  15. Palladium-Catalyzed Arylation of Alkyl Sulfenate Anions.

    PubMed

    Jia, Tiezheng; Zhang, Mengnan; Jiang, Hui; Wang, Carol Y; Walsh, Patrick J

    2015-11-01

    A unique palladium-catalyzed arylation of alkyl sulfenate anions is introduced that affords aryl alkyl sulfoxides in high yields. Due to the base sensitivity of the starting sulfoxides, sulfenate anion intermediates, and alkyl aryl sulfoxide products, the use of a mild method to generate alkyl sulfenate anions was crucial to the success of this process. Thus, a fluoride triggered elimination strategy was employed with alkyl 2-(trimethylsilyl)ethyl sulfoxides to liberate the requisite alkyl sulfenate anion intermediates. In the presence of palladium catalysts with bulky monodentate phosphines (SPhos and Cy-CarPhos) and aryl bromides or chlorides, alkyl sulfenate anions were readily arylated. Moreover, the thermal fragmentation and the base promoted elimination of alkyl sulfoxides was overridden. The alkyl sulfenate anion arylation exhibited excellent chemoselectivity in the presence of functional groups, such as anilines and phenols, which are also known to undergo palladium catalyzed arylation reactions.

  16. Diversity-oriented approach to macrocyclic cyclophane derivatives by Suzuki-Miyaura cross-coupling and olefin metathesis as key steps.

    PubMed

    Kotha, Sambasivarao; Chavan, Arjun S; Shaikh, Mobin

    2012-01-01

    Palladium-catalyzed Suzuki-Miyaura (SM) cross-coupling reaction with allylboronic acid pinacol ester and titanium assisted cross-metathesis (CM)/ring-closing metathesis (RCM) cascade has been used to synthesize macrocyclic cyclophane derivatives.

  17. Palladium-Catalyzed Enantioselective 1,1-Fluoroarylation of Aminoalkenes

    PubMed Central

    2016-01-01

    The development of an enantioselective palladium-catalyzed 1,1-fluoroarylation of unactivated aminoalkenes is described. The reaction uses arylboronic acids as the arene source and Selectfluor as the fluorine source to generate benzylic fluorides in good yields with excellent enantioselectivities. This transformation, likely proceeding through an oxidative Heck mechanism, affords 1,1-difunctionalized alkene products. PMID:26378886

  18. Palladium-catalyzed direct arylation and cyclization of o-iodobiaryls to a library of tetraphenylenes

    NASA Astrophysics Data System (ADS)

    Zhu, Chendan; Zhao, Yue; Wang, Di; Sun, Wei-Yin; Shi, Zhuangzhi

    2016-09-01

    Aryl–aryl bond formation constitutes one of the most important subjects in organic synthesis. The recent developments in direct arylation reactions forming aryl–aryl bond have emerged as very attractive alternatives to traditional cross-coupling reactions. Here, we describe a general palladium-catalyzed direct arylation and cyclization of o-iodobiaryls to build a library of tetraphenylenes. This transformation represents one of the very few examples of C-H activation process that involves simultaneous formation of two aryl–aryl bonds. Oxygen plays a vital role by ensuring high reactivity, with air as the promoter furnished the best results. We anticipate this ligand-free and aerobic catalytic system will simplify the synthesis of tetraphenylenes as many of the reported methods involve use of preformed organometallic reagents and will lead to the discovery of highly efficient new direct arylation process.

  19. Palladium-catalyzed direct arylation and cyclization of o-iodobiaryls to a library of tetraphenylenes.

    PubMed

    Zhu, Chendan; Zhao, Yue; Wang, Di; Sun, Wei-Yin; Shi, Zhuangzhi

    2016-01-01

    Aryl-aryl bond formation constitutes one of the most important subjects in organic synthesis. The recent developments in direct arylation reactions forming aryl-aryl bond have emerged as very attractive alternatives to traditional cross-coupling reactions. Here, we describe a general palladium-catalyzed direct arylation and cyclization of o-iodobiaryls to build a library of tetraphenylenes. This transformation represents one of the very few examples of C-H activation process that involves simultaneous formation of two aryl-aryl bonds. Oxygen plays a vital role by ensuring high reactivity, with air as the promoter furnished the best results. We anticipate this ligand-free and aerobic catalytic system will simplify the synthesis of tetraphenylenes as many of the reported methods involve use of preformed organometallic reagents and will lead to the discovery of highly efficient new direct arylation process. PMID:27629701

  20. Palladium-catalyzed direct arylation and cyclization of o-iodobiaryls to a library of tetraphenylenes

    PubMed Central

    Zhu, Chendan; Zhao, Yue; Wang, Di; Sun, Wei-Yin; Shi, Zhuangzhi

    2016-01-01

    Aryl–aryl bond formation constitutes one of the most important subjects in organic synthesis. The recent developments in direct arylation reactions forming aryl–aryl bond have emerged as very attractive alternatives to traditional cross-coupling reactions. Here, we describe a general palladium-catalyzed direct arylation and cyclization of o-iodobiaryls to build a library of tetraphenylenes. This transformation represents one of the very few examples of C-H activation process that involves simultaneous formation of two aryl–aryl bonds. Oxygen plays a vital role by ensuring high reactivity, with air as the promoter furnished the best results. We anticipate this ligand-free and aerobic catalytic system will simplify the synthesis of tetraphenylenes as many of the reported methods involve use of preformed organometallic reagents and will lead to the discovery of highly efficient new direct arylation process. PMID:27629701

  1. Synthesis of 5-alkenylated D4T analogues via the Pd-catalyzed cross-coupling reaction.

    PubMed

    Ciurea, A; Fossey, C; Benzaria, S; Gavriliu, D; Delbederi, Z; Lelong, B; Ladurée, D; Aubertin, A M; Kirn, A

    2001-09-01

    The target compounds 5-[N-(6-amino-hexyl)-acrylamide]-2',3'-didehydro-2',3'-dideoxy-uridine (12) and 5-[N-[5-(methoxycarbonyl)-pentyl]-acrylamide]-2',3'-didehydro-2',3'- dideoxy-uridine (15) were prepared by the palladium acetate-triphenylphosphine-catalyzed reaction of the 5'-O-acetyl-5-iodo-d4T analogue (3). These compounds 12 and 15 can be used to prepare nucleotide probes carrying fluorescent labels and were nevertheless screened for their anti-HIV activity. The biological data demonstrated that none of them were active against HIV-1. PMID:11580192

  2. Palladium-Catalyzed Oxidative Domino Carbocyclization–Arylation of Bisallenes

    PubMed Central

    2016-01-01

    Herein we report a highly efficient and site-selective palladium-catalyzed oxidative carbocyclization–arylation reaction of bisallenes and arylboronic acids under operationally simple conditions for the selective synthesis of cyclohexadiene derivatives. The palladium source and the solvent proved to be crucial for the selectivity and the reactivity displayed. Interestingly, in the absence of the nucleophile, an oxidative carbocyclization-β-elimination pathway predominates. The reaction conditions are compatible with a wide range of functional groups, and the reaction exhibits broad substrate scope. Furthermore, key information regarding the mechanism was obtained using control experiments and kinetic studies. PMID:27761298

  3. Formal Direct Cross-Coupling of Phenols with Amines.

    PubMed

    Chen, Zhengwang; Zeng, Huiying; Girard, Simon A; Wang, Feng; Chen, Ning; Li, Chao-Jun

    2015-11-23

    The transition-metal-catalyzed amination of aryl halides has been the most powerful method for the formation of aryl amines over the past decades. Phenols are regarded as ideal alternatives to aryl halides as coupling partners in cross-couplings. An efficient palladium-catalyzed formal cross-coupling of phenols with various amines and anilines has now been developed. A variety of substituted phenols were compatible with the standard reaction conditions. Secondary and tertiary aryl amines could thus be synthesized in moderate to excellent yields. PMID:26531683

  4. New Palladium-Catalyzed Approaches to Heterocycles and Carbocycles

    SciTech Connect

    Qinhua Huang

    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{sub 2}, ICl, PhSeCl, PhSCl and p-O{sub 2}NC{sub 6}H{sub 4}SCl 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 excellent 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

  5. Catalysis in the Service of Green Chemistry: Nobel Prize-Winning Palladium-Catalysed Cross-Couplings, Run in Water at Room Temperature

    PubMed Central

    Lipshutz, Bruce H.; Taft, Benjamin R.; Abela, Alexander R.; Ghorai, Subir; Krasovskiy, Arkady; Duplais, Christophe

    2012-01-01

    Palladium-catalysed cross-couplings, in particular Heck, Suzuki-Miyaura and Negishi reactions developed over three decades ago, are routinely carried out in organic solvents. However, alternative media are currently of considerable interest given an increasing emphasis on making organic processes ‘greener’; for example, by minimising organic waste in the form of organic solvents. Water is the obvious leading candidate in this regard. Hence, this review focuses on the application of micellar catalysis, in which a ‘designer’ surfactant enables these award-winning coupling reactions to be run in water at room temperature. PMID:23555153

  6. TPGS-750-M: a second-generation amphiphile for metal-catalyzed cross-couplings in water at room temperature.

    PubMed

    Lipshutz, Bruce H; Ghorai, Subir; Abela, Alexander R; Moser, Ralph; Nishikata, Takashi; Duplais, Christophe; Krasovskiy, Arkady; Gaston, Ricky D; Gadwood, Robert C

    2011-06-01

    An environmentally benign surfactant (TPGS-750-M), a diester composed of racemic α-tocopherol, MPEG-750, and succinic acid, has been designed and readily prepared as an effective nanomicelle-forming species for general use in metal-catalyzed cross-coupling reactions in water. Several "name" reactions, including Heck, Suzuki-Miyaura, Sonogashira, and Negishi-like couplings, have been studied using this technology, as have aminations, C-H activations, and olefin metathesis reactions. Physical data in the form of DLS and cryo-TEM measurements suggest that particle size and shape are key elements in achieving high levels of conversion and, hence, good isolated yields of products. This new amphiphile will soon be commercially available.

  7. A General Strategy for the Synthesis of Enantiomerically Pure Azetidines and Aziridines through Nickel-Catalyzed Cross-Coupling.

    PubMed

    Jensen, Kim L; Nielsen, Dennis U; Jamison, Timothy F

    2015-05-11

    In this communication, we report a straightforward synthesis of enantiomerically pure 2-alkyl azetidines. The protocol is based on a highly regioselective nickel-catalyzed cross-coupling of aliphatic organozinc reagents with an aziridine that features a tethered thiophenyl group. Activation by methylation transforms the sulfide into an excellent leaving group and triggers the formation of the 2-substituted azetidine core structure by cyclization. In addition, we have expanded this concept to the synthesis of enantiomerically pure, terminal alkyl aziridines. Coupling of a TMS-protected aziridine alcohol, followed by acidic work-up to remove the silyl group, provides 1,2-amino alcohol products that are readily cyclized to aziridines. Both of these sequences display excellent functional group tolerance and deliver the desired azetidine and aziridine products in good to excellent yields. PMID:25820027

  8. Palladium Catalyzed Intramolecular Acylcyanation of Alkenes Using α-Iminonitriles

    PubMed Central

    Rondla, Naveen R.; Ogilvie, Jodi M.; Pan, Zhongda

    2014-01-01

    Reported here is a palladium catalyzed intramolecular acylcyanation of alkenes using α-iminonitriles. Through this method, highly functionalized indanones are synthesized in moderate to high yields using Pd(PPh3)4, without need for any additional ligands, and a common Lewis acid (ZnCl2). Additionally, the reaction tolerates substitution at various positions on the aromatic ring including electron donating, and electron withdrawing groups. PMID:24980625

  9. Stereoselective Synthesis of Trisubstituted Alkenes through Sequential Iron-Catalyzed Reductive anti-Carbozincation of Terminal Alkynes and Base-Metal-Catalyzed Negishi Cross-Coupling.

    PubMed

    Cheung, Chi Wai; Hu, Xile

    2015-12-01

    The stereoselective synthesis of trisubstituted alkenes is challenging. Here, we show that an iron-catalyzed anti-selective carbozincation of terminal alkynes can be combined with a base-metal-catalyzed cross-coupling to prepare trisubstituted alkenes in a one-pot reaction and with high regio- and stereocontrol. Cu-, Ni-, and Co-based catalytic systems are developed for the coupling of sp-, sp(2) -, and sp(3) -hybridized carbon electrophiles, respectively. The method encompasses a large substrate scope, as various alkynyl, aryl, alkenyl, acyl, and alkyl halides are suitable coupling partners. Compared with conventional carbometalation reactions of alkynes, the current method avoids pre-made organometallic reagents and has a distinct stereoselectivity.

  10. Highly efficient palladium precatalysts of homoscorpionate bispyrazolyl ligands for the more challenging Suzuki-Miyaura cross-coupling of aryl chlorides.

    PubMed

    John, Alex; Shaikh, Mobin M; Butcher, Ray J; Ghosh, Prasenjit

    2010-08-21

    Highly efficient palladium precatalysts {[RN{-(CH(2))(n)-pz(3,5-Me)(2)}(2)]PdCl(2)}(m) [m = n = 1; R = 2,6-Me(2)C(6)H(3) (1), 2,4,6-Me(3)C(6)H(2) (2), CH(2)Ph (3) and m = n = 2; R = CH(2)Ph (4)] of a series of homoscorpionate bispyrazolyl ligands for the Suzuki-Miyaura cross-coupling of the more challenging aryl chloride substrates are reported. In particular, the palladium 1-4 precatalysts carried out the Suzuki-Miyaura cross-coupling of a wide variety of aryl chloride substrates bearing electron withdrawing, electron donating and heteroaryl substituents. Remarkably enough, the molecular structure determination of the 1-4 precatalysts by X-ray diffraction studies revealed the presence of anagostic [C-H...Pd] type interactions in the mononuclear 1-3 complexes of methylene bridged bispyrazolyl ligands whereas the ethylene bridged analog 4 yielded an interesting dimeric 20-membered macrometallacyclic complex devoid of any such interaction. PMID:20607167

  11. Highly efficient palladium precatalysts of homoscorpionate bispyrazolyl ligands for the more challenging Suzuki-Miyaura cross-coupling of aryl chlorides.

    PubMed

    John, Alex; Shaikh, Mobin M; Butcher, Ray J; Ghosh, Prasenjit

    2010-08-21

    Highly efficient palladium precatalysts {[RN{-(CH(2))(n)-pz(3,5-Me)(2)}(2)]PdCl(2)}(m) [m = n = 1; R = 2,6-Me(2)C(6)H(3) (1), 2,4,6-Me(3)C(6)H(2) (2), CH(2)Ph (3) and m = n = 2; R = CH(2)Ph (4)] of a series of homoscorpionate bispyrazolyl ligands for the Suzuki-Miyaura cross-coupling of the more challenging aryl chloride substrates are reported. In particular, the palladium 1-4 precatalysts carried out the Suzuki-Miyaura cross-coupling of a wide variety of aryl chloride substrates bearing electron withdrawing, electron donating and heteroaryl substituents. Remarkably enough, the molecular structure determination of the 1-4 precatalysts by X-ray diffraction studies revealed the presence of anagostic [C-H...Pd] type interactions in the mononuclear 1-3 complexes of methylene bridged bispyrazolyl ligands whereas the ethylene bridged analog 4 yielded an interesting dimeric 20-membered macrometallacyclic complex devoid of any such interaction.

  12. Asymmetric copper-catalyzed C-N cross-couplings induced by visible light.

    PubMed

    Kainz, Quirin M; Matier, Carson D; Bartoszewicz, Agnieszka; Zultanski, Susan L; Peters, Jonas C; Fu, Gregory C

    2016-02-12

    Despite a well-developed and growing body of work in copper catalysis, the potential of copper to serve as a photocatalyst remains underexplored. Here we describe a photoinduced copper-catalyzed method for coupling readily available racemic tertiary alkyl chloride electrophiles with amines to generate fully substituted stereocenters with high enantioselectivity. The reaction proceeds at -40°C under excitation by a blue light-emitting diode and benefits from the use of a single, Earth-abundant transition metal acting as both the photocatalyst and the source of asymmetric induction. An enantioconvergent mechanism transforms the racemic starting material into a single product enantiomer. PMID:26912852

  13. Density functional theory investigation on Pd-catalyzed cross-coupling of azoles with aryl thioethers.

    PubMed

    Yang, Yi-Meng; Dang, Zhi-Min; Yu, Hai-Zhu

    2016-05-11

    In the present study, a density functional theory (DFT) study has been carried out on the Pd-catalyzed coupling of azoles with aryl thioethers. Our effort is mainly put into identifying the most feasible catalytic cycle, and especially the origin of chemoselectivity for the exclusive aromatic Csp(2)-S bond activation (in the presence of an alkyl Csp(3)-S bond). The coupling mainly consists of three steps: C-S activation, NaO(t)Bu mediated C-H palladation, and reductive elimination. The Csp(2)-S activation is favored over Csp(3)-S activation, and thus di(hetero)aryls are the predicted products. This conclusion well reproduces Wang's recent experimental observations. The rate- and chemoselectivity determining steps of the C-H/Csp(2)-S activation mechanism are C-H palladation and C-S activation steps, respectively. Analyzing the origin of chemoselectivity, we found that the easiness of Pd catalyzed C-S activation is independent of the C-S bond strengths in thioether substrates. By contrast, d-π* backdonation in Csp(2)-S-Pd intermediates is the main driving force for the favorable Csp(2)-S activation (over the Csp(3)-S activation). PMID:27097907

  14. Palladium-Catalyzed Environmentally Benign Acylation.

    PubMed

    Suchand, Basuli; Satyanarayana, Gedu

    2016-08-01

    Recent trends in research have gained an orientation toward developing efficient strategies using innocuous reagents. The earlier reported transition-metal-catalyzed carbonylations involved either toxic carbon monoxide (CO) gas as carbonylating agent or functional-group-assisted ortho sp(2) C-H activation (i.e., ortho acylation) or carbonylation by activation of the carbonyl group (i.e., via the formation of enamines). Contradicting these methods, here we describe an environmentally benign process, [Pd]-catalyzed direct carbonylation starting from simple and commercially available iodo arenes and aldehydes, for the synthesis of a wide variety of ketones. Moreover, this method comprises direct coupling of iodoarenes with aldehydes without activation of the carbonyl and also without directing group assistance. Significantly, the strategy was successfully applied to the synthesis n-butylphthalide and pitofenone. PMID:27377566

  15. The design, synthesis and validation of recoverable and readily reusable siloxane transfer agents for Pd-catalyzed cross-coupling reactions.

    PubMed

    Martinez-Solorio, Dionicio; Hoye, Adam T; Nguyen, Minh H; Smith, Amos B

    2013-05-17

    The development of competent, recoverable and reusable 1-oxa-2-silacyclopentene (siloxane) transfer agents for Pd-catalyzed cross-coupling reactions (CCRs) of organolithium reagents with aryl and alkenyl iodides has been achieved. Drawbacks of the first-generation siloxane-transfer agent (1), relating to facile recovery for potential recycling, have been addressed.

  16. 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. PMID:24478275

  17. Hydrosilane and bismuth-accelerated palladium catalyzed aerobic oxidative esterification of benzylic alcohols with air.

    PubMed

    Bai, Xing-Feng; Ye, Fei; Zheng, Long-Sheng; Lai, Guo-Qiao; Xia, Chun-Gu; Xu, Li-Wen

    2012-09-01

    In a palladium-catalyzed oxidative esterification, hydrosilane can serve as an activator of palladium catalyst with bismuth, thus leading to a novel ligand- and silver-free palladium catalyst system for facile oxidative esterification of a variety of benzylic alcohols in good yields.

  18. Hydrosilane and bismuth-accelerated palladium catalyzed aerobic oxidative esterification of benzylic alcohols with air.

    PubMed

    Bai, Xing-Feng; Ye, Fei; Zheng, Long-Sheng; Lai, Guo-Qiao; Xia, Chun-Gu; Xu, Li-Wen

    2012-09-01

    In a palladium-catalyzed oxidative esterification, hydrosilane can serve as an activator of palladium catalyst with bismuth, thus leading to a novel ligand- and silver-free palladium catalyst system for facile oxidative esterification of a variety of benzylic alcohols in good yields. PMID:22814568

  19. Palladium-catalyzed cross-coupling of sterically demanding boronic acids with α-bromocarbonyl compounds.

    PubMed

    Zimmermann, Bettina; Dzik, Wojciech I; Himmler, Thomas; Goossen, Lukas J

    2011-10-01

    A catalyst system generated in situ from Pd(dba)(2) and tri(o-tolyl)phosphine mediates the coupling of arylboronic acids with alkyl α-bromoacetates under formation of arylacetic acid esters at unprecedented low loadings. The new protocol, which involves potassium fluoride as the base and catalytic amounts of benzyltriethylammonium bromide as a phase transfer catalyst, is uniquely effective for the synthesis of sterically demanding arylacetic acid derivatives.

  20. Synthesis of Dihydrobenzofurans via Palladium-Catalyzed Heteroannulations

    SciTech Connect

    Roman Vladimirovich Rozhkov

    2004-12-19

    Palladium-catalyzed heteroannulation of 1,3-dienes with 3-iodo-2-alkenols, and 2-iodo-2-alkenols, as well as their amino analogs, affords the corresponding cyclic ethers and amines respectively. The presence of a {beta}-hydrogen in the vinylic halide results in {beta}-hydride elimination giving the corresponding alkyne. The presence of a bulky group in the {alpha}-position of the vinylic halide results in failure or reduced amounts of annulation products. A chloride source, pyridine base and electron-rich phosphine are essential for this reaction.

  1. The Palladium-Catalyzed Trifluoromethylation of Vinyl Sulfonates

    PubMed Central

    Cho, Eun Jin; Buchwald, Stephen L.

    2011-01-01

    A method for the palladium-catalyzed trifluoromethylation of cyclohexenyl sulfonates has been developed. Various cyclohexenyl triflates and nonaflates underwent trifluoromethylation under mild reaction conditions using a catalyst system composed of Pd(dba)2 or [(allyl)PdCl]2 and the monodentate biaryl phosphine ligand tBuXPhos. The trifluoromethyl anion (CF3−) or its equivalent for the process was generated in situ from TMSCF3 in combination with KF or TESCF3 in combintion with RbF. PMID:22111687

  2. Pd-catalyzed steroid reactions.

    PubMed

    Czajkowska-Szczykowska, Dorota; Morzycki, Jacek W; Wojtkielewicz, Agnieszka

    2015-05-01

    We review the most important achievements of the last decade in the field of steroid synthesis in the presence of palladium catalysts. Various palladium-catalyzed cross-coupling reactions, including Heck, Suzuki, Stille, Sonogashira, Negishi and others, are exemplified with steroid transformations.

  3. Iron(II) Active Species in Iron-Bisphosphine Catalyzed Kumada and Suzuki-Miyaura Cross-Couplings of Phenyl Nucleophiles and Secondary Alkyl Halides.

    PubMed

    Daifuku, Stephanie L; Kneebone, Jared L; Snyder, Benjamin E R; Neidig, Michael L

    2015-09-01

    While previous studies have identified FeMes2(SciOPP) as the active catalyst species in iron-SciOPP catalyzed Kumada cross-coupling of mesitylmagnesium bromide and primary alkyl halides, the active catalyst species in cross-couplings with phenyl nucleophiles, where low valent iron species might be prevalent due to accessible reductive elimination pathways, remains undefined. In the present study, in situ Mössbauer and magnetic circular dichroism spectroscopic studies combined with inorganic syntheses and reaction studies are employed to evaluate the in situ formed iron species and identify the active catalytic species in iron-SciOPP catalyzed Suzuki-Miyaura and Kumada cross-couplings of phenyl nucleophiles and secondary alkyl halides. While reductive elimination to form Fe(η(6)-biphenyl)(SciOPP) occurs upon reaction of FeCl2(SciOPP) with phenyl nucleophiles, this iron(0) species is not found to be kinetically competent for catalysis. Importantly, mono- and bis-phenylated iron(II)-SciOPP species that form prior to reductive elimination are identified, where both species are found to be reactive toward electrophile at catalytically relevant rates. The higher selectivity toward the formation of cross-coupled product observed for the monophenylated species combined with the undertransmetalated nature of the in situ iron species in both Kumada and Suzuki-Miyaura reactions indicates that Fe(Ph)X(SciOPP) (X = Br, Cl) is the predominant reactive species in cross-coupling. Overall, these studies demonstrate that low-valent iron is not required for the generation of highly reactive species for effective aryl-alkyl cross-couplings. PMID:26266698

  4. Iron(II) Active Species in Iron-Bisphosphine Catalyzed Kumada and Suzuki-Miyaura Cross-Couplings of Phenyl Nucleophiles and Secondary Alkyl Halides.

    PubMed

    Daifuku, Stephanie L; Kneebone, Jared L; Snyder, Benjamin E R; Neidig, Michael L

    2015-09-01

    While previous studies have identified FeMes2(SciOPP) as the active catalyst species in iron-SciOPP catalyzed Kumada cross-coupling of mesitylmagnesium bromide and primary alkyl halides, the active catalyst species in cross-couplings with phenyl nucleophiles, where low valent iron species might be prevalent due to accessible reductive elimination pathways, remains undefined. In the present study, in situ Mössbauer and magnetic circular dichroism spectroscopic studies combined with inorganic syntheses and reaction studies are employed to evaluate the in situ formed iron species and identify the active catalytic species in iron-SciOPP catalyzed Suzuki-Miyaura and Kumada cross-couplings of phenyl nucleophiles and secondary alkyl halides. While reductive elimination to form Fe(η(6)-biphenyl)(SciOPP) occurs upon reaction of FeCl2(SciOPP) with phenyl nucleophiles, this iron(0) species is not found to be kinetically competent for catalysis. Importantly, mono- and bis-phenylated iron(II)-SciOPP species that form prior to reductive elimination are identified, where both species are found to be reactive toward electrophile at catalytically relevant rates. The higher selectivity toward the formation of cross-coupled product observed for the monophenylated species combined with the undertransmetalated nature of the in situ iron species in both Kumada and Suzuki-Miyaura reactions indicates that Fe(Ph)X(SciOPP) (X = Br, Cl) is the predominant reactive species in cross-coupling. Overall, these studies demonstrate that low-valent iron is not required for the generation of highly reactive species for effective aryl-alkyl cross-couplings.

  5. Iron(II) Active Species in Iron–Bisphosphine Catalyzed Kumada and Suzuki–Miyaura Cross-Couplings of Phenyl Nucleophiles and Secondary Alkyl Halides

    PubMed Central

    2015-01-01

    While previous studies have identified FeMes2(SciOPP) as the active catalyst species in iron–SciOPP catalyzed Kumada cross-coupling of mesitylmagnesium bromide and primary alkyl halides, the active catalyst species in cross-couplings with phenyl nucleophiles, where low valent iron species might be prevalent due to accessible reductive elimination pathways, remains undefined. In the present study, in situ Mössbauer and magnetic circular dichroism spectroscopic studies combined with inorganic syntheses and reaction studies are employed to evaluate the in situ formed iron species and identify the active catalytic species in iron–SciOPP catalyzed Suzuki–Miyaura and Kumada cross-couplings of phenyl nucleophiles and secondary alkyl halides. While reductive elimination to form Fe(η6-biphenyl)(SciOPP) occurs upon reaction of FeCl2(SciOPP) with phenyl nucleophiles, this iron(0) species is not found to be kinetically competent for catalysis. Importantly, mono- and bis-phenylated iron(II)–SciOPP species that form prior to reductive elimination are identified, where both species are found to be reactive toward electrophile at catalytically relevant rates. The higher selectivity toward the formation of cross-coupled product observed for the monophenylated species combined with the undertransmetalated nature of the in situ iron species in both Kumada and Suzuki–Miyaura reactions indicates that Fe(Ph)X(SciOPP) (X = Br, Cl) is the predominant reactive species in cross-coupling. Overall, these studies demonstrate that low-valent iron is not required for the generation of highly reactive species for effective aryl-alkyl cross-couplings. PMID:26266698

  6. Pd-catalyzed arylation of chlorotrifluoroethylene using arylboronic acids.

    PubMed

    Yamamoto, Tetsuya; Yamakawa, Tetsu

    2012-07-01

    The palladium-catalyzed cross-coupling of chlorotrifluoroethylene and arylboronic acids proceeds in the presence of a base and H(2)O to provide α,β,β-trifluorostyrene derivatives in satisfactory yields. PMID:22691065

  7. Nickel-Catalyzed Cross Couplings of Benzylic Ammonium Salts and Boronic Acids: Stereospecific Formation of Diarylethanes via C–N Bond Activation

    PubMed Central

    Maity, Prantik; Shacklady-McAtee, Danielle M.; Yap, Glenn P. A.; Sirianni, Eric R.; Watson, Mary P.

    2014-01-01

    We have developed a nickel-catalyzed cross coupling of benzylic ammonium triflates with aryl boronic acids to afford diarylmethanes and diarylethanes. This reaction proceeds under mild reaction conditions and with exceptional functional group tolerance. Further, it transforms branched benzylic ammonium salts to diarylethanes with excellent chirality transfer, offering a new strategy for the synthesis of highly enantioenriched diarylethanes from readily available chiral benzylic amines. PMID:23268734

  8. Cross-coupling reaction of alkyl halides with grignard reagents catalyzed by Ni, Pd, or Cu complexes with pi-carbon ligand(s).

    PubMed

    Terao, Jun; Kambe, Nobuaki

    2008-11-18

    Transition metal-catalyzed cross-coupling reactions of organic halides and pseudo-halides containing a C-X bond (X = I, Br, Cl, OTf, OTs, etc.) with organometallic reagents are among the most important transformations for carbon-carbon bond formation between a variety of sp, sp(2), and sp(3)-hybridized carbon atoms. In particular, researchers have widely employed Ni- and Pd-catalyzed cross-coupling to synthesize complex organic structures from readily available components. The catalytic cycle of this process comprises oxidative addition, transmetalation, and reductive elimination steps. In these reactions, various organometallic reagents could bear a variety of R groups (alkyl, vinyl, aryl, or allyl), but the coupling partner has been primarily limited to sp and sp(2) carbon compounds: alkynes, alkenes, and arenes. With alkyl coupling partners, these reactions typically run into two problems within the catalytic cycle. First, oxidative addition of alkyl halides to a metal catalyst is generally less efficient than that of aryl or alkenyl compounds. Second, the alkylmetal intermediates formed tend to undergo intramolecular beta-hydrogen elimination. In this Account, we describe our efforts to overcome these problems for Ni and Pd chemistry. We have developed new catalytic systems that do not involve M(0) species but proceed via an anionic complex as the key intermediate. For example, we developed a unique cross-coupling reaction of alkyl halides with organomagnesium or organozinc reagents catalyzed by using a 1,3-butadiene as the additive. This reaction follows a new catalytic pathway: the Ni or Pd catalyst reacts first with R-MgX to form an anionic complex, which then reacts with alkyl halides. Bis-dienes were also effective additives for the Ni-catalyzed cross-coupling reaction of organozinc reagents with alkyl halides. This catalytic system tolerates a wide variety of functional groups, including nitriles, ketones, amides, and esters. In addition, we have extended

  9. Transition-metal-catalyzed carbon-heteroatom three-component cross-coupling reactions: a new concept for carbothiolation of alkynes.

    PubMed

    Kuniyasu, Hitoshi; Kurosawa, Hideo

    2002-06-17

    The deep-seated understanding of flexible ligand behavior of thiolate on transition-metals has paved the way to achieve metal-catalyzed carbothiolations of terminal alkynes. The strategy of the reaction is quite simple: 1) generation of the complex with C-Pt-S fragments formed after the Pd-catalyzed C-S bond-forming cross-coupling reaction, 2) insertion of an alkyne into Pt-S bond to form the complex with a C-Pt-C fragment, and 3) C-C bond-forming reductive elimination.

  10. Palladium-catalyzed Suzuki-Miyaura coupling of amides by carbon-nitrogen cleavage: general strategy for amide N-C bond activation.

    PubMed

    Meng, Guangrong; Szostak, Michal

    2016-06-15

    The first palladium-catalyzed Suzuki-Miyaura cross-coupling of amides with boronic acids for the synthesis of ketones by sterically-controlled N-C bond activation is reported. The transformation is characterized by operational simplicity using bench-stable, commercial reagents and catalysts, and a broad substrate scope, including substrates with electron-donating and withdrawing groups on both coupling partners, steric-hindrance, heterocycles, halides, esters and ketones. The scope and limitations are presented in the synthesis of >60 functionalized ketones. Mechanistic studies provide insight into the catalytic cycle of the cross-coupling, including the first experimental evidence for Pd insertion into the amide N-C bond. The synthetic utility is showcased by a gram-scale cross-coupling and cross-coupling at room temperature. Most importantly, this process provides a blueprint for the development of a plethora of metal catalyzed reactions of typically inert amide bonds via acyl-metal intermediates. A unified strategy for amide bond activation to enable metal insertion into N-C amide bond is outlined ().

  11. Palladium-catalyzed Suzuki-Miyaura coupling of amides by carbon-nitrogen cleavage: general strategy for amide N-C bond activation.

    PubMed

    Meng, Guangrong; Szostak, Michal

    2016-06-15

    The first palladium-catalyzed Suzuki-Miyaura cross-coupling of amides with boronic acids for the synthesis of ketones by sterically-controlled N-C bond activation is reported. The transformation is characterized by operational simplicity using bench-stable, commercial reagents and catalysts, and a broad substrate scope, including substrates with electron-donating and withdrawing groups on both coupling partners, steric-hindrance, heterocycles, halides, esters and ketones. The scope and limitations are presented in the synthesis of >60 functionalized ketones. Mechanistic studies provide insight into the catalytic cycle of the cross-coupling, including the first experimental evidence for Pd insertion into the amide N-C bond. The synthetic utility is showcased by a gram-scale cross-coupling and cross-coupling at room temperature. Most importantly, this process provides a blueprint for the development of a plethora of metal catalyzed reactions of typically inert amide bonds via acyl-metal intermediates. A unified strategy for amide bond activation to enable metal insertion into N-C amide bond is outlined (). PMID:26864384

  12. 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

  13. Palladium-catalyzed direct coupling of 2-vinylanilines and isocyanides: an efficient synthesis of 2-aminoquinolines.

    PubMed

    Wang, Lijie; Ferguson, Jamie; Zeng, Fanlong

    2015-12-21

    Palladium-catalyzed oxidative coupling of 2-vinylanilines and isocyanides constitutes a direct, facile, and efficient approach to 2-aminoquinolines. The procedure, employing palladium acetate and silver carbonate, is attractive in terms of assembly efficiency, functional group tolerance, and operational simplicity. A variety of 2-aminoquinolines were prepared in good to excellent yields. PMID:26455948

  14. 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...

  15. The palladium-catalyzed intermolecular C-H chalcogenation of arenes.

    PubMed

    Qiu, Renhua; Reddy, Vutukuri Prakash; Iwasaki, Takanori; Kambe, Nobuaki

    2015-01-01

    Palladium catalyzes the intermolecular chalcogenation of carbazole, 2-phenylpyridine, benzo[h]quinolone, and indole derivatives with disulfides and diselenides via selective C-H bond cleavage, providing a convenient route to thio and selenoethers. PMID:25437148

  16. Synthesis of 2-indolylphosphines by palladium-catalyzed annulation of 1-alkynylphosphine sulfides with 2-iodoanilines.

    PubMed

    Kondoh, Azusa; Yorimitsu, Hideki; Oshima, Koichiro

    2010-04-01

    Palladium-catalyzed annulation of 1-alkynylphosphine sulfides with 2-iodoanilines followed by desulfidation affords 3-substituted 2-indolylphosphines. This annulation/desulfidation sequential protocol offers a conceptually new approach to bulky heteroarylphosphines.

  17. Palladium-Catalyzed Dearomative Cyclocarbonylation by C-N Bond Activation.

    PubMed

    Yu, Hui; Zhang, Guoying; Huang, Hanmin

    2015-09-01

    A fundamentally novel approach to bioactive quinolizinones is based on the palladium-catalyzed intramolecular cyclocarbonylation of allylamines. [Pd(Xantphos)I2 ], which features a very large bite angle, has been found to facilitate the rapid carbonylation of azaarene-substituted allylamines into bioactive quinolizinones in good to excellent yields. This transformation represents the first dearomative carbonylation and is proposed to proceed by palladium-catalyzed CN bond activation, dearomatization, CO insertion, and a Heck reaction.

  18. An Electron-Poor C64 Nanographene by Palladium-Catalyzed Cascade C-C Bond Formation: One-Pot Synthesis and Single-Crystal Structure Analysis.

    PubMed

    Seifert, Sabine; Shoyama, Kazutaka; Schmidt, David; Würthner, Frank

    2016-05-23

    Herein, we report the one-pot synthesis of an electron-poor nanographene containing dicarboximide groups at the corners. We efficiently combined palladium-catalyzed Suzuki-Miyaura cross-coupling and dehydrohalogenation to synthesize an extended two-dimensional π-scaffold of defined size in a single chemical operation starting from N-(2,6-diisopropylphenyl)-4,5-dibromo-1,8-naphthalimide and a tetrasubstituted pyrene boronic acid ester as readily accessible starting materials. The reaction of these precursors under the conditions commonly used for Suzuki-Miyaura cross-coupling afforded a C64 nanographene through the formation of ten C-C bonds in a one-pot process. Single-crystal X-ray analysis unequivocally confirmed the structure of this unique extended aromatic molecule with a planar geometry. The optical and electrochemical properties of this largest ever synthesized planar electron-poor nanographene skeleton were also analyzed.

  19. Nickel-Catalyzed Reductive Cross-Coupling of Benzyl Chlorides with Aryl Chlorides/Fluorides: A One-Pot Synthesis of Diarylmethanes.

    PubMed

    Zhang, Jie; Lu, Gusheng; Xu, Jin; Sun, Hongmei; Shen, Qi

    2016-06-17

    The first nickel-catalyzed, magnesium-mediated reductive cross-coupling between benzyl chlorides and aryl chlorides or fluorides is reported. A variety of diarylmethanes can be prepared in good to excellent yields in a one-pot manner using easy-to-access mixed PPh3/NHC Ni(II) complexes of Ni(PPh3)(NHC)Br2 (NHC = 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene, IPr, 1a; 1,3-di-tert-butylimidazol-2-ylidene, ItBu, 1b) as catalyst precursors. Activation of polychloroarenes or chemoselective cross-coupling based on the difference in catalytic activity between 1a and 1b is used to construct oligo-diarylmethane motifs. PMID:27268781

  20. Oxidative palladium(II) catalysis: A highly efficient and chemoselective cross-coupling method for carbon-carbon bond formation under base-free and nitrogenous-ligand conditions.

    PubMed

    Yoo, Kyung Soo; Yoon, Cheol Hwan; Mishra, Rajesh K; Jung, Young Chun; Yi, Sung Wook; Jung, Kyung Woon

    2006-12-20

    We report herein the development of a general and mild protocol of oxygen-promoted Pd(II) catalysis resulting in the selective cross-couplings of alkenyl- and arylboron compounds with various olefins. Unlike most cross-coupling reactions, this new methodology works well even in the absence of bases, consequently averting undesired homo-couplings. Nitrogen-based ligands including dimethyl-phenanathroline enhance reactivities and offer a highly efficient and stereoselective methodology to overcome challenging substrate limitations. For instance, oxidative palladium(II) catalysis is effective with highly substituted alkenes and cyclic alkenes, which are known to be incompatible with other known catalytic conditions. Most examined reactions progressed smoothly to completion at low temperatures and in short times. These interesting results provide mechanistic insights and utilities for a new paradigm of palladium catalytic cycles without bases.

  1. 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.

  2. Directing Group in Decarboxylative Cross-Coupling: Copper-Catalyzed Site-Selective C-N Bond Formation from Nonactivated Aliphatic Carboxylic Acids.

    PubMed

    Liu, Zhao-Jing; Lu, Xi; Wang, Guan; Li, Lei; Jiang, Wei-Tao; Wang, Yu-Dong; Xiao, Bin; Fu, Yao

    2016-08-01

    Copper-catalyzed directed decarboxylative amination of nonactivated aliphatic carboxylic acids is described. This intramolecular C-N bond formation reaction provides efficient access to the synthesis of pyrrolidine and piperidine derivatives as well as the modification of complex natural products. Moreover, this reaction presents excellent site-selectivity in the C-N bond formation step through the use of directing group. Our work can be considered as a big step toward controllable radical decarboxylative carbon-heteroatom cross-coupling. PMID:27439145

  3. Synthesis of hexahydropyrrolo[2,1-a]isoquinoline compound libraries through a Pictet-Spengler cyclization/metal-catalyzed cross coupling/amidation sequence.

    PubMed

    Petersen, Rico; Cohrt, A Emil; Petersen, Michael Åxman; Wu, Peng; Clausen, Mads H; Nielsen, Thomas E

    2015-06-01

    Molecular libraries of natural product-like and structurally diverse compounds are attractive in early drug discovery campaigns. In here, we present synthetic methodology for library production of hexahydropyrrolo[2,1-a]isoquinoline (HPIQ) compounds. Two advanced HPIQ intermediates, both incorporating two handles for diversification, were synthesized through an oxidative cleavage/Pictet-Spengler reaction sequence in high overall yields. A subsequent metal-catalyzed cross coupling/amidation protocol was developed and its utility in library synthesis was validated by construction of a 20-membered natural product-like molecular library in good overall yields.

  4. Cp*Rh(III)-Catalyzed Cross-Coupling of Alkyltrifluoroborate with α-Diazomalonates for C(sp(3))-C(sp(3)) Bond Formation.

    PubMed

    Lu, Yin-Suo; Yu, Wing-Yiu

    2016-03-18

    A Cp*Rh(III)-catalyzed cross-coupling of alkyltrifluoroborate with α-diazomalonates was developed; the C(sp(3))-C(sp(3)) bond coupled products were formed in up to 97% yields. The reaction tolerates some useful functional groups, including ketone, ester, amide, ether, sulfonyl, and thiophene. Electrospray ionization mass spectrometry (ESI-MS) analysis revealed the formation of a distinct molecular species corresponding to σ-alkylrhodium(III) complexes. The successful diazo coupling reaction may be attributed to coordination of the amide group that promotes stability of the alkylrhodium(III) complex through the formation of a five-membered metallacycle. PMID:26926387

  5. Synthesis of hexahydropyrrolo[2,1-a]isoquinoline compound libraries through a Pictet-Spengler cyclization/metal-catalyzed cross coupling/amidation sequence.

    PubMed

    Petersen, Rico; Cohrt, A Emil; Petersen, Michael Åxman; Wu, Peng; Clausen, Mads H; Nielsen, Thomas E

    2015-06-01

    Molecular libraries of natural product-like and structurally diverse compounds are attractive in early drug discovery campaigns. In here, we present synthetic methodology for library production of hexahydropyrrolo[2,1-a]isoquinoline (HPIQ) compounds. Two advanced HPIQ intermediates, both incorporating two handles for diversification, were synthesized through an oxidative cleavage/Pictet-Spengler reaction sequence in high overall yields. A subsequent metal-catalyzed cross coupling/amidation protocol was developed and its utility in library synthesis was validated by construction of a 20-membered natural product-like molecular library in good overall yields. PMID:25703308

  6. Hydroxyl-Directed Cross-Coupling: A Scalable Synthesis of Debromohamigeran E and Other Targets of Interest.

    PubMed

    Blaisdell, Thomas P; Morken, James P

    2015-07-15

    A hydroxyl functional group positioned β to a pinacol boronate can serve to direct palladium-catalyzed cross-coupling reactions. This feature can be used to control the reaction site in multiply borylated substrates and can activate boronates for reaction that would otherwise be unreactive.

  7. Nickel-Catalyzed Suzuki-Miyaura Cross-Coupling in a Green Alcohol Solvent for an Undergraduate Organic Chemistry Laboratory

    ERIC Educational Resources Information Center

    Hie, Liana; Chang, Jonah J.; Garg, Neil K.

    2015-01-01

    A modern undergraduate organic chemistry laboratory experiment involving the Suzuki-Miyaura coupling is reported. Although Suzuki-Miyaura couplings typically employ palladium catalysts in environmentally harmful solvents, this experiment features the use of inexpensive nickel catalysis, in addition to a "green" alcohol solvent. The…

  8. Palladium-Catalyzed Intramolecular Carbene Insertion into C(sp(3) )-H Bonds.

    PubMed

    Solé, Daniel; Mariani, Francesco; Bennasar, M-Lluïsa; Fernández, Israel

    2016-05-23

    A palladium-catalyzed carbene insertion into C(sp(3) )-H bonds leading to pyrrolidines was developed. The coupling reaction can be catalyzed by both Pd(0) and Pd(II) , is regioselective, and shows a broad functional group tolerance. This reaction is the first example of palladium-catalyzed C(sp(3) )-C(sp(3) ) bond assembly starting from diazocarbonyl compounds. DFT calculations revealed that this direct C(sp(3) )-H bond functionalization reaction involves an unprecedented concerted metalation-deprotonation step.

  9. New directing groups for metal-catalyzed asymmetric carbon-carbon bond-forming processes: stereoconvergent alkyl-alkyl Suzuki cross-couplings of unactivated electrophiles.

    PubMed

    Wilsily, Ashraf; Tramutola, Francesco; Owston, Nathan A; Fu, Gregory C

    2012-04-01

    The ability of two common protected forms of amines (carbamates and sulfonamides) to serve as directing groups in Ni-catalyzed Suzuki reactions has been exploited in the development of catalytic asymmetric methods for cross-coupling unactivated alkyl electrophiles. Racemic secondary bromides and chlorides undergo C-C bond formation in a stereoconvergent process in good ee at room temperature in the presence of a commercially available Ni complex and chiral ligand. Structure-enantioselectivity studies designed to elucidate the site of binding to Ni (the oxygen of the carbamate and of the sulfonamide) led to the discovery that sulfones also serve as useful directing groups for asymmetric Suzuki cross-couplings of racemic alkyl halides. To our knowledge, this investigation provides the first examples of the use of sulfonamides or sulfones as effective directing groups in metal-catalyzed asymmetric C-C bond-forming reactions. A mechanistic study established that transmetalation occurs with retention of stereochemistry and that the resulting Ni-C bond does not undergo homolysis in subsequent stages of the catalytic cycle.

  10. Copper-catalyzed alkyl-alkyl cross-coupling reactions using hydrocarbon additives: efficiency of catalyst and roles of additives.

    PubMed

    Iwasaki, Takanori; Imanishi, Reiko; Shimizu, Ryohei; Kuniyasu, Hitoshi; Terao, Jun; Kambe, Nobuaki

    2014-09-19

    Cross-coupling of alkyl halides with alkyl Grignard reagents proceeds with extremely high TONs of up to 1230000 using a Cu/unsaturated hydrocarbon catalytic system. Alkyl fluorides, chlorides, bromides, and tosylates are all suitable electrophiles, and a TOF as high as 31200 h(-1) was attained using an alkyl iodide. Side reactions of this catalytic system, i.e., reduction, dehydrohalogenation (elimination), and the homocoupling of alkyl halides, occur in the absence of additives. It appears that the reaction involves the β-hydrogen elimination of alkylcopper intermediates, giving rise to olefins and Cu-H species, and that this process triggers both side reactions and the degradation of the Cu catalyst. The formed Cu-H promotes the reduction of alkyl halides to give alkanes and Cu-X or the generation of Cu(0), probably by disproportionation, which can oxidatively add to alkyl halides to yield olefins and, in some cases, homocoupling products. Unsaturated hydrocarbon additives such as 1,3-butadiene and phenylpropyne play important roles in achieving highly efficient cross-coupling by suppressing β-hydrogen elimination, which inhibits both the degradation of the Cu catalyst and undesirable side reactions.

  11. Copper-catalyzed alkyl-alkyl cross-coupling reactions using hydrocarbon additives: efficiency of catalyst and roles of additives.

    PubMed

    Iwasaki, Takanori; Imanishi, Reiko; Shimizu, Ryohei; Kuniyasu, Hitoshi; Terao, Jun; Kambe, Nobuaki

    2014-09-19

    Cross-coupling of alkyl halides with alkyl Grignard reagents proceeds with extremely high TONs of up to 1230000 using a Cu/unsaturated hydrocarbon catalytic system. Alkyl fluorides, chlorides, bromides, and tosylates are all suitable electrophiles, and a TOF as high as 31200 h(-1) was attained using an alkyl iodide. Side reactions of this catalytic system, i.e., reduction, dehydrohalogenation (elimination), and the homocoupling of alkyl halides, occur in the absence of additives. It appears that the reaction involves the β-hydrogen elimination of alkylcopper intermediates, giving rise to olefins and Cu-H species, and that this process triggers both side reactions and the degradation of the Cu catalyst. The formed Cu-H promotes the reduction of alkyl halides to give alkanes and Cu-X or the generation of Cu(0), probably by disproportionation, which can oxidatively add to alkyl halides to yield olefins and, in some cases, homocoupling products. Unsaturated hydrocarbon additives such as 1,3-butadiene and phenylpropyne play important roles in achieving highly efficient cross-coupling by suppressing β-hydrogen elimination, which inhibits both the degradation of the Cu catalyst and undesirable side reactions. PMID:25010426

  12. Palladium-catalyzed imidoylative cyclization of α-isocyanoacetamides: efficient access to C2-diversified oxazoles.

    PubMed

    Wang, Jian; Luo, Shuang; Huang, Jinbo; Mao, Tingting; Zhu, Qiang

    2014-08-25

    A novel procedure for the synthesis of C2-diversified oxazoles, through palladium-catalyzed imidoylative cyclization of α-isocyanoacetamides with aryl, vinyl, alkynyl halides, or triflates, was developed. Migratory insertion of isocyanide into a Csp3-palladium(II) intermediate in a cascade process was also realized, generating alkyl-substituted oxazoles. Therefore, oxazoles functionalized at the C2 position with sp, sp(2), and sp(3) hybridized carbon atoms are accessible by applying this method.

  13. Palladium(II)-catalyzed direct alkoxylation of arenes: evidence for solvent-assisted concerted metalation deprotonation.

    PubMed

    Anand, Megha; Sunoj, Raghavan B

    2011-09-16

    Density functional theory investigations on the mechanism of palladium acetate catalyzed direct alkoxylation of N-methoxybenzamide in methanol reveal that the key steps involve solvent-assisted N-H as well as C-H bond activations. The transition state for the critical palladium-carbon bond formation through a concerted metalation deprotonation (CMD) process leading to a palladacycle intermediate has been found to be more stable in the methanol-assisted pathway as compared to an unassisted route.

  14. Palladium-catalyzed direct C2 arylation of N-substituted indoles with 1-aryltriazenes.

    PubMed

    Liu, Can; Miao, Tao; Zhang, Lei; Li, Pinhua; Zhang, Yicheng; Wang, Lei

    2014-09-01

    A novel and efficient palladium-catalyzed C2 arylation of N-substituted indoles with 1-aryltriazenes for the synthesis of 2-arylindoles was developed. In the presence of BF3⋅OEt2 and palladium(II) acetate (Pd(OAc)2), N-substituted indoles reacted with 1-aryltriazenes in N,N-dimethylacetamide (DMAC) to afford the corresponding aryl-indole-type products in good to excellent yields.

  15. Functionalization of Hydrogenated Graphene: Transition-Metal-Catalyzed Cross-Coupling Reactions of Allylic C-H Bonds.

    PubMed

    Chua, Chun Kiang; Sofer, Zdeněk; Pumera, Martin

    2016-08-26

    The chemical functionalization of hydrogenated graphene can modify its physical properties and lead to better processability. Herein, we describe the chemical functionalization of hydrogenated graphene through a dehydrogenative cross-coupling reaction between an allylic C-H bond and the α-C-H bond of tetrahydrothiophen-3-one using Cu(OTf)2 as the catalyst and DDQ as the oxidant. The chemical functionalization was confirmed by X-ray photoelectron spectroscopy and Fourier transform infrared spectroscopy and visualized by scanning electron microscopy. The functionalized hydrogenated graphene material demonstrated improved dispersion stability in water, bringing new quality to the elusive hydrogenated graphene (graphane) materials. Hydrogenated graphene provides broad possibilities for chemical modifications owing to its reactivity.

  16. Silylesterification of oxidized multi-wall carbon nanotubes by catalyzed dehydrogenative cross-coupling between carboxylic and hydrosilane functions

    NASA Astrophysics Data System (ADS)

    Seffer, J.-F.; Detriche, S.; Nagy, J. B.; Delhalle, J.; Mekhalif, Z.

    2014-06-01

    Surface modification of oxidized carbon nanotubes (O-CNTs) with silicon based anchoring groups (R-SiR3) is a relatively uncommon approach of the CNTs functionalization. Hydrosilane derivatives constitute an attractive subclass of compounds for silanization reactions on the CNTs surface. In this work, we report on the ZnCl2 catalytically controlled reaction (hydrosilane dehydrogenative cross-coupling, DHCC) of fluorinated hydrosilane probes with the carboxylic functions present on the surface of oxidized multi-wall carbon nanotubes. Carbon nanotubes functionalized with essentially alcohol groups are also used to compare the selectivity of zinc chloride toward carboxylic groups. To assess the efficiency of functionalization, X-ray Photoelectron Spectroscopy is used to determine the qualitative and quantitative composition of the different samples. Solubility tests on the oxidized and silanized MWNTs are also carried out in the framework of the Hansen Solubility Parameters (HSP) theory to apprehend at another scale the effect of DHCC.

  17. Functionalization of Hydrogenated Graphene: Transition-Metal-Catalyzed Cross-Coupling Reactions of Allylic C-H Bonds.

    PubMed

    Chua, Chun Kiang; Sofer, Zdeněk; Pumera, Martin

    2016-08-26

    The chemical functionalization of hydrogenated graphene can modify its physical properties and lead to better processability. Herein, we describe the chemical functionalization of hydrogenated graphene through a dehydrogenative cross-coupling reaction between an allylic C-H bond and the α-C-H bond of tetrahydrothiophen-3-one using Cu(OTf)2 as the catalyst and DDQ as the oxidant. The chemical functionalization was confirmed by X-ray photoelectron spectroscopy and Fourier transform infrared spectroscopy and visualized by scanning electron microscopy. The functionalized hydrogenated graphene material demonstrated improved dispersion stability in water, bringing new quality to the elusive hydrogenated graphene (graphane) materials. Hydrogenated graphene provides broad possibilities for chemical modifications owing to its reactivity. PMID:27496619

  18. Mild Palladium-Catalyzed Cyanation of (Hetero)aryl Halides and Triflates in Aqueous Media

    PubMed Central

    2016-01-01

    A mild, efficient, and low-temperature palladium-catalyzed cyanation of (hetero)aryl halides and triflates is reported. Previous palladium-catalyzed cyanations of (hetero)aryl halides have required higher temperatures to achieve good catalytic activity. This current reaction allows the cyanation of a general scope of (hetero)aryl halides and triflates at 2–5 mol % catalyst loadings with temperatures ranging from rt to 40 °C. This mild method was applied to the synthesis of lersivirine, a reverse transcriptase inhibitor. PMID:25555140

  19. Synthesis of alpha-acyl-functionalized azacycles by Pd-catalyzed cross-coupling reactions of alpha-alkoxyboronates with lactam-derived vinyl triflates.

    PubMed

    Occhiato, Ernesto G; Prandi, Cristina; Ferrali, Alessandro; Guarna, Antonio; Deagostino, Annamaria; Venturello, Paolo

    2002-10-01

    Alkoxydienyl- and alkoxystyrylboronates were used for Pd-catalyzed cross-coupling reactions with lactam-derived vinyl triflates. The hydrolysis of the coupling products with alkoxystyrylboronates provided the corresponding alpha-acyl-substituted 3,4-dihydro-(2H)-pyridines and 2,3,4,5-tetrahydroazepines in good to high yields. The hydrolysis of the coupling products with alkoxydienylboronates, performed in the presence of Amberlyst 15, resulted in a Nazarov-type cyclization that afforded hexahydro[1]pyrindin-7-ones and 3,4,5,6,7,8-hexahydro-(2H)-cyclopenta[b]azepin-8-ones. This methodology represents a novel and efficient procedure for the preparation of these classes of azacyclic compounds. PMID:12354013

  20. Direct N-acylation of azoles via a metal-free catalyzed oxidative cross-coupling strategy.

    PubMed

    Zhao, Jingjing; Li, Pan; Xia, Chungu; Li, Fuwei

    2014-05-11

    The KI-catalyzed N-acylation of azoles via direct oxidative coupling of C-H and N-H bonds has been developed. It could be smoothly scaled up to gram synthesis of acyl azoles. The reaction occurred by the coupling of acyl radicals and azoles to form the acyl azole radical anion, followed by its further oxidation.

  1. Use of a palladium(II)-catalyzed oxidative kinetic resolution in synthetic efforts toward bielschowskysin

    PubMed Central

    Meyer, Michael E.; Phillips, John H.; Ferreira, Eric M.; Stoltz, Brian M.

    2013-01-01

    Progress toward the cyclobutane core of bielshowskysin is reported. The core was thought to arise from a cyclopropane intermediate via a furan-mediated cyclopropane fragmentation, followed by a 1,4-Michael addition. The synthesis of the cyclopropane intermediate utilizes a Suzuki coupling reaction, an esterification with 2-diazoacetoacetic acid, and a copper catalyzed cyclopropanation. An alcohol intermediate within the synthetic route was obtained in high enantiopurity via a highly selective palladium(II)-catalyzed oxidative kinetic resolution (OKR). PMID:23913988

  2. Mechanistic Insights into the Palladium-Catalyzed Aziridination of Aliphatic Amines by C-H Activation.

    PubMed

    Smalley, Adam P; Gaunt, Matthew J

    2015-08-26

    Detailed kinetic studies and computational investigations have been performed to elucidate the mechanism of a palladium-catalyzed C-H activation aziridination. A theoretical rate law has been derived that matches with experimental observations and has led to an improvement in the reaction conditions. Acetic acid was found to be beneficial in controlling the formation of an off-cycle intermediate, allowing a decrease in catalyst loading and improved yields. Density functional theory (DFT) studies were performed to examine the selectivities observed in the reaction. Evidence for electronic-controlled regioselectivity for the cyclopalladation step was obtained by a distortion-interaction analysis, whereas the aziridination product was justified through dissociation of acetic acid from the palladium(IV) intermediate preceding the product-forming reductive elimination step. The understanding of this reaction mechanism under the synthesis conditions should provide valuable assistance in the comprehension and design of palladium-catalyzed reactions on similar systems. PMID:26247373

  3. Mechanistic Insights into the Palladium-Catalyzed Aziridination of Aliphatic Amines by C-H Activation.

    PubMed

    Smalley, Adam P; Gaunt, Matthew J

    2015-08-26

    Detailed kinetic studies and computational investigations have been performed to elucidate the mechanism of a palladium-catalyzed C-H activation aziridination. A theoretical rate law has been derived that matches with experimental observations and has led to an improvement in the reaction conditions. Acetic acid was found to be beneficial in controlling the formation of an off-cycle intermediate, allowing a decrease in catalyst loading and improved yields. Density functional theory (DFT) studies were performed to examine the selectivities observed in the reaction. Evidence for electronic-controlled regioselectivity for the cyclopalladation step was obtained by a distortion-interaction analysis, whereas the aziridination product was justified through dissociation of acetic acid from the palladium(IV) intermediate preceding the product-forming reductive elimination step. The understanding of this reaction mechanism under the synthesis conditions should provide valuable assistance in the comprehension and design of palladium-catalyzed reactions on similar systems.

  4. Palladium-Catalyzed Annulation of Arynes by ortho-Halobenzamides: Synthesis of Phenanthridinones

    PubMed Central

    Lu, Chun; Dubrovskiy, Anton V.

    2012-01-01

    The palladium-catalyzed annulation of arynes by substituted o-halobenzamides produces N-substituted phenanthridinones in good yields. This methodology provides this important heterocyclic ring system in a single step by simultaneous C-C and C-N bond formation, under relatively mild reaction conditions, and tolerates a variety of functional groups. PMID:23013049

  5. Palladium-Catalyzed C–H Arylation of 1,2,3-Triazoles

    PubMed Central

    Zhang, Chengwei; You, Lin; Chen, Chuo

    2016-01-01

    Palladium(II) acetate, in combination with triphenylphosphine, catalyzes direct arylation of 1,4-disubstituted 1,2,3-triazoles effectively. This C–H arylation reaction provides facile access to fully substituted triazoles with well-defined regiochemistry. PMID:27669198

  6. Palladium-catalyzed dehydrogenative coupling of terminal alkynes with secondary phosphine oxides.

    PubMed

    Yang, Jia; Chen, Tieqiao; Zhou, Yongbo; Yin, Shuangfeng; Han, Li-Biao

    2015-02-28

    The dehydrogenative coupling of terminal alkynes with secondary phosphine oxides is developed. In the presence of a silver additive, palladium acetate could efficiently catalyze the dehydrocoupling of secondary phosphine oxides with a variety of terminal alkynes to produce the corresponding alkynylphosphine oxides in high yields. A reaction mechanism is proposed. PMID:25627893

  7. Enantioselective Palladium-Catalyzed Oxidative β,β-Fluoroarylation of α,β-Unsaturated Carbonyl Derivatives.

    PubMed

    Miró, Javier; Del Pozo, Carlos; Toste, F Dean; Fustero, Santos

    2016-07-25

    The site-selective palladium-catalyzed three-component coupling of deactivated alkenes, arylboronic acids, and N-fluorobenzenesulfonimide is disclosed herein. The developed methodology establishes a general, modular, and step-economical approach to the stereoselective β-fluorination of α,β-unsaturated systems. PMID:27272390

  8. Palladium-catalyzed oxidative carbonylation of ethylene and propylene by butyl nitrite and carbon monoxide

    SciTech Connect

    Brechot, P.; Chauvin, Y.; Commereuc, D.; Saussine, L. )

    1990-01-01

    In the oxidative carbonylation of ethylene by carbon monoxide and butyl nitrite catalyzed by PdCl{sub 2}(PhCN){sub 2} in the presence of triphenylphosphine, the pentacoordinated tetravalent palladium complex PdCl{sub 2}(COOBu)NO(PPh{sub 3}) has been isolated and has proved to be an intermediate in the catalytic cycle.

  9. Palladium-Catalyzed C-H Arylation of 1,2,3-Triazoles.

    PubMed

    Zhang, Chengwei; You, Lin; Chen, Chuo

    2016-01-01

    Palladium(II) acetate, in combination with triphenylphosphine, catalyzes direct arylation of 1,4-disubstituted 1,2,3-triazoles effectively. This C-H arylation reaction provides facile access to fully substituted triazoles with well-defined regiochemistry. PMID:27669198

  10. Palladium/copper-catalyzed oxidative C-H alkenylation/N-dealkylative carbonylation of tertiary anilines.

    PubMed

    Shi, Renyi; Lu, Lijun; Zhang, Hua; Chen, Borui; Sha, Yuchen; Liu, Chao; Lei, Aiwen

    2013-09-27

    C-H/C-N activation: The first palladium/copper-catalyzed aerobic oxidative C-H alkenylation/N-dealkylative carbonylation of tertiary anilines has been developed. Various functional groups were tolerated and acrylic ester could also be suitable substrates. This transformation provided efficient and straightforward synthesis of biologically active 3-methyleneindolin-2-one derivatives from cheap and simple substrates.

  11. Transition-metal catalyzed oxidative cross-coupling reactions to form C-C bonds involving organometallic reagents as nucleophiles.

    PubMed

    Shi, Wei; Liu, Chao; Lei, Aiwen

    2011-05-01

    Transition-metal-catalyzed coupling reactions have become a versatile tool for chemical bond formation. From the variation of the coupling partners, coupling reactions can be classified into three models: traditional coupling, reductive coupling and oxidative coupling. The oxidative coupling, which is different from the traditional coupling, occurs between two nucleophiles. This critical review focuses on transition-metal-catalyzed oxidative coupling reactions involving organometallic reagents as nucleophiles. Since the scope of the oxidative coupling is highly diversified, this paper only reviews the oxidative coupling reactions concerning C-C bond formation, including the coupling between organometal reagents and hydrocarbons as well as coupling between two organometal reagents. Since terminal alkynes are normally activated by metal salts and in situ form the alkynyl metal reagents in coupling reactions, they are directly considered as organometal reagents in this review. Intramolecular oxidative couplings and oxidative cyclizations are not included in this critical review. Moreover, there are many examples of oxidative coupling leading to the formation of functional materials, such as the oxidative polymerization of thiophenes. Since several reviews in these areas have been published they are not included in this review either (99 references).

  12. Nickel-catalyzed cross-coupling reactions of o-carboranyl with aryl iodides: facile synthesis of 1-aryl-o-carboranes and 1,2-diaryl-o-carboranes.

    PubMed

    Tang, Cen; Xie, Zuowei

    2015-06-22

    A nickel-catalyzed arylation at the carbon center of o-carborane cages has been developed, thus leading to the preparation of a series of 1-aryl-o-carboranes and 1,2-diaryl-o-carboranes in high yields upon isolation. This method represents the first example of transition metal catalyzed C,C'-diarylation by cross-coupling reactions of o-carboranyl with aryl iodides.

  13. Palladium-catalyzed directing group-assisted C8-triflation of naphthalenes.

    PubMed

    Yang, Zhi-Wei; Zhang, Qi; Jiang, Yuan-Ye; Li, Lei; Xiao, Bin; Fu, Yao

    2016-05-10

    The transition-metal-catalyzed direct triflation of naphthyl amides and naphthyl ketones has been accomplished for the first time. Benzophenone (BP) was found to be a suitable ligand for the cross-coupling reactions. Density functional theory (DFT) calculations revealed that excessive amounts of HOTf inhibit the reductive elimination of the C-F bond to realize the unusual reductive elimination of the C-OTf bond. PMID:27117543

  14. Palladium catalyzed C3-arylation of 4-hydroxy-2-pyridones.

    PubMed

    Anagnostaki, Elissavet E; Fotiadou, Anna D; Demertzidou, Vera; Zografos, Alexandros L

    2014-07-01

    The direct arylation of N-substituted-4-hydroxy-2-pyridones with aryl boronic acids has been achieved under palladium catalysis. The mild reaction conditions applied in this method and the use of a conventional catalytic system offer an attractive protocol for the efficient synthesis of a variety of 3-arylated products.

  15. Palladium-catalyzed intramolecular cyclization of ynamides: synthesis of 4-halo-oxazolones.

    PubMed

    Huang, Hai; He, Guangke; Zhu, Guohao; Zhu, Xiaolin; Qiu, Shineng; Zhu, Hongjun

    2015-04-01

    A mild and efficient methodology involving Pd(PPh3)4-catalyzed intramolecular cyclization of N-alkynyl alkyloxycarbamates with CuCl2 or CuBr2 for the synthesis of 4-halo-oxazolones was developed. This reaction exhibiting good functional tolerance provided a new, efficient, and rapid synthetic process to 4-halo-oxazolones. The resulting 4-halo-oxazolones can serve as great potential precursors for the 3,4,5-trisubstituted oxazolones via a Pd-catalyzed cross-coupling reaction.

  16. Palladium(II)-Catalyzed Enantioselective Synthesis of α-(Trifluoromethyl)arylmethylamines.

    PubMed

    Johnson, Thomas; Luo, Bo; Lautens, Mark

    2016-06-17

    We describe a method for the synthesis of α-(trifluoromethyl)arylmethylamines that consists of the palladium(II)-catalyzed addition of arylboroxines to imines derived from trifluoroacetaldehyde. Palladium acetate is used as a catalyst with electron-neutral or electron-rich arylboroxines, and it was found that addition of an ammonium or silver salt was crucial to promote the reaction of electron-poor boroxines. With (S)-t-Bu-PyOX as the chiral ligand, this method delivers a variety of α-trifluoromethylated amines in 57-91% yield and with greater than 92% ee in most cases. PMID:27246788

  17. Olefin Preparation via Palladium-Catalyzed Oxidative De-Azotative and De-Sulfitative Internal Cross-Coupling of Sulfonylhydrazones.

    PubMed

    Tan, Hongyu; Houpis, Ioannis; Liu, Renmao; Wang, Youchu; Chen, Zhilong

    2015-07-17

    A novel reactivity of sulfonylhydrazones under Pd catalysis is described, where SO2 and N2 are formally extruded to afford the product of an apparent internal coupling reaction. The reaction is effective with both carbocyclic and heterocyclic aromatic precursors.

  18. Palladium-catalyzed cross-coupling of styrenes with aryl methyl ketones in ionic liquids: direct access to cyclopropanes.

    PubMed

    Cotugno, Pietro; Monopoli, Antonio; Ciminale, Francesco; Milella, Antonella; Nacci, Angelo

    2014-12-01

    The combined use of Pd(OAc)2 , Cu(OAc)2 , and dioxygen in molten tetrabutylammonium acetate (TBAA) promotes an unusual cyclopropanation reaction between aryl methyl ketones and styrenes. The process is a dehydrogenative cyclizing coupling that involves a twofold CH activation at the α-position of the ketone. The substrate scope highlights the flexibility of the catalyst; a reaction mechanism is also proposed. PMID:25283684

  19. Methane ignition catalyzed by in situ generated palladium nanoparticles

    SciTech Connect

    Shimizu, T.; Abid, A.D.; Poskrebyshev, G.; Wang, H.; Nabity, J.; Engel, J.; Yu, J.; Wickham, D.; Van Devener, B.; Anderson, S.L.; Williams, S.

    2010-03-15

    Catalytic ignition of methane over the surfaces of freely-suspended and in situ generated palladium nanoparticles was investigated experimentally and numerically. The experiments were conducted in a laminar flow reactor. The palladium precursor was a compound (Pd(THD){sub 2}, THD: 2,2,6,6-tetramethyl-3,5-heptanedione) dissolved in toluene and injected into the flow reactor as a fine aerosol, along with a methane-oxygen-nitrogen mixture. For experimental conditions chosen in this study, non-catalytic, homogeneous ignition was observed at a furnace temperature of {proportional_to}1123 K, whereas ignition of the same mixture with the precursor was found to be {proportional_to}973 K. In situ production of Pd/PdO nanoparticles was confirmed by scanning mobility, transmission electron microscopy and X-ray photoelectron spectroscopy analyses of particles collected at the reactor exit. The catalyst particle size distribution was log-normal. Depending on the precursor loading, the median diameter ranged from 10 to 30 nm. The mechanism behind catalytic ignition was examined using a combined gas-phase and gas-surface reaction model. Simulation results match the experiments closely and suggest that palladium nanocatalyst significantly shortens the ignition delay times of methane-air mixtures over a wide range of conditions. (author)

  20. Amine-Catalyzed Highly Regioselective and Stereoselective C(sp(2) )-C(sp(2) ) Cross-Coupling of Naphthols with trans-α,β-Unsaturated Aldehydes.

    PubMed

    Hu, Yang; Ma, Yueyue; Sun, Rengwei; Yu, Xinhong; Xie, Hexin; Wang, Wei

    2015-09-01

    A metal-free C(sp(2) )-C(sp(2) ) cross-coupling approach to highly congested (E)-α-naphtholylenals from simple naphthols and enals is described. The mild reaction conditions with pyridine hydrobromideperbromide (PHBP) as the bromination reagent in the presence of piperidine or diphenylprolinol trimethylsilyl (TMS) ether as promoters enable the process in good yields and with high chemoselectivity, regioselectivity, and stereoselectivity. The process involves an unprecedented pathway of in situ regioselective 4-bromination of 1-naphthols and the subsequent unusual aromatic nucleophilic substitution of the resulting 4-bromo-1-naphthols with the α-C(sp(2) ) of enals through a Michael-type Friedel-Crafts alkylation-dearomatization followed by a cyclopropanation ring-opening cascade process. The noteworthy features of this strategy are highlighted by the highly efficient creation of a C(sp(2) )-C(sp(2) ) bond from readily available unfunctionalized naphthols and enals catalyzed by non-metal, readily available cyclic secondary amines under mild reaction conditions. PMID:26096893

  1. Enantioselective palladium-catalyzed C-H functionalization of indoles using an axially chiral 2,2'-bipyridine ligand.

    PubMed

    Gao, Xiang; Wu, Bo; Huang, Wen-Xue; Chen, Mu-Wang; Zhou, Yong-Gui

    2015-10-01

    A palladium-catalyzed enantioselective CH functionalization of indoles was achieved with an axially chiral 2,2'-bipyridine ligand, thus providing the desired indol-3-acetate derivatives with up to 98 % ee. Moreover, the reaction protocol was also effective for asymmetric OH insertion reaction of phenols using α-aryl-α-diazoacetates. This represents the first successful application of bipyridine ligands with axial chirality in palladium-catalyzed carbene migratory insertion reactions.

  2. Enhanced catalytic degradation process of o-nitrochlorobenzene by palladium-catalyzed fe0 particles.

    PubMed

    Xu, Xin-hua; Zhou, Hong-yi; Zhou, Mi; Wang, Da-hui

    2005-01-01

    Over Pd/Fe bimetallic catalyst, o-nitrochlorobenzene (o-NCB), at a concentration of 20 mg/L in aqueous solutions, is rapidly converted to o-chloroaniline (o-CAN) first, and then quickly dechlorinated to aniline(AN) and Cl-, without other intermediate reaction products. The aminated and dechlorinated reactions are believed to take place on the surface site of the Pd/Fe. The o-NCB removal efficiency and the next dechlorination rate increase with an increase of bulk loading of palladium and catalysts addition due to the increase of both the surface loading of palladium and the total surface area. These results indicate that reduction, amination and dechlorination of o-NCB by palladium-catalyzed Fe0 particles, can be designed for remediation of contaminated groundwater.

  3. Stereospecific cross-coupling of secondary organotrifluoroborates: potassium 1-(benzyloxy)alkyltrifluoroborates.

    PubMed

    Molander, Gary A; Wisniewski, Steven R

    2012-10-10

    Potassium 1-(alkoxy/acyloxy)alkyltrifluoroborates have been synthesized through a copper-catalyzed diboration of aldehydes and subsequent conversion of the resulting potassium 1-(hydroxy)alkyltrifluoroborates. The palladium-catalyzed Suzuki-Miyaura reaction employing the potassium 1-(benzyloxy)alkyltrifluoroborates with aryl and heteroaryl chlorides provides access to protected secondary alcohols in high yields. The β-hydride elimination pathway is avoided through use of the benzyl protecting group, which is proposed to stabilize the diorganopalladium intermediate by coordination of the arene to the metal center. This cross-coupling is stereospecific with complete retention of stereochemistry. PMID:23025482

  4. Bridging organometallics and quantum chemical topology: Understanding electronic relocalisation during palladium-catalyzed reductive elimination.

    PubMed

    de Courcy, Benoit; Derat, Etienne; Piquemal, Jean-Philip

    2015-06-01

    This article proposes to bridge two fields, namely organometallics and quantum chemical topology. To do so, Palladium-catalyzed reductive elimination is studied. Such reaction is a classical elementary step in organometallic chemistry, where the directionality of electrons delocalization is not well understood. New computational evidences highlighting the accepted mechanism are proposed following a strategy coupling quantum theory of atoms in molecules and electron localization function topological analyses and enabling an extended quantification of donated/back-donated electrons fluxes along reaction paths going beyond the usual Dewar-Chatt-Duncanson model. Indeed, if the ligands coordination mode (phosphine, carbene) is commonly described as dative, it appears that ligands lone pairs stay centered on ligands as electrons are shared between metal and ligand with strong delocalization toward the latter. Overall, through strong trans effects coming from the carbon involved in the reductive elimination, palladium delocalizes its valence electrons not only toward phosphines but interestingly also toward the carbene. As back-donation increases during reductive elimination, one of the reaction key components is the palladium ligands ability to accept electrons. The rationalization of such electronic phenomena gives new directions for the design of palladium-catalyzed systems. PMID:25899703

  5. Bridging organometallics and quantum chemical topology: Understanding electronic relocalisation during palladium-catalyzed reductive elimination.

    PubMed

    de Courcy, Benoit; Derat, Etienne; Piquemal, Jean-Philip

    2015-06-01

    This article proposes to bridge two fields, namely organometallics and quantum chemical topology. To do so, Palladium-catalyzed reductive elimination is studied. Such reaction is a classical elementary step in organometallic chemistry, where the directionality of electrons delocalization is not well understood. New computational evidences highlighting the accepted mechanism are proposed following a strategy coupling quantum theory of atoms in molecules and electron localization function topological analyses and enabling an extended quantification of donated/back-donated electrons fluxes along reaction paths going beyond the usual Dewar-Chatt-Duncanson model. Indeed, if the ligands coordination mode (phosphine, carbene) is commonly described as dative, it appears that ligands lone pairs stay centered on ligands as electrons are shared between metal and ligand with strong delocalization toward the latter. Overall, through strong trans effects coming from the carbon involved in the reductive elimination, palladium delocalizes its valence electrons not only toward phosphines but interestingly also toward the carbene. As back-donation increases during reductive elimination, one of the reaction key components is the palladium ligands ability to accept electrons. The rationalization of such electronic phenomena gives new directions for the design of palladium-catalyzed systems.

  6. Electronic Structure and Bonding in Iron(II) and Iron(I) Complexes Bearing Bisphosphine Ligands of Relevance to Iron-Catalyzed C–C Cross-Coupling

    PubMed Central

    2015-01-01

    Chelating phosphines are effective additives and supporting ligands for a wide array of iron-catalyzed cross-coupling reactions. While recent studies have begun to unravel the nature of the in situ-formed iron species in several of these reactions, including the identification of the active iron species, insight into the origin of the differential effectiveness of bisphosphine ligands in catalysis as a function of their backbone and peripheral steric structures remains elusive. Herein, we report a spectroscopic and computational investigation of well-defined FeCl2(bisphosphine) complexes (bisphosphine = SciOPP, dpbz, tBudppe, or Xantphos) and known iron(I) variants to systematically discern the relative effects of bisphosphine backbone character and steric substitution on the overall electronic structure and bonding within their iron complexes across oxidation states implicated to be relevant in catalysis. Magnetic circular dichroism (MCD) and density functional theory (DFT) studies demonstrate that common o-phenylene and saturated ethyl backbone motifs result in small but non-negligible perturbations to 10Dq(Td) and iron–bisphosphine bonding character at the iron(II) level within isostructural tetrahedra as well as in five-coordinate iron(I) complexes FeCl(dpbz)2 and FeCl(dppe)2. Notably, coordination of Xantphos to FeCl2 results in a ligand field significantly reduced relative to those of its iron(II) partners, where a large bite angle and consequent reduced iron–phosphorus Mayer bond orders (MBOs) could play a role in fostering the unique ability of Xantphos to be an effective additive in Kumada and Suzuki–Miyaura alkyl–alkyl cross-couplings. Furthermore, it has been found that the peripheral steric bulk of the SciOPP ligand does little to perturb the electronic structure of FeCl2(SciOPP) relative to that of the analogous FeCl2(dpbz) complex, potentially suggesting that differences in the steric properties of these ligands might be more important in

  7. 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.

  8. Synthesis of Alkenylphosphonates through Palladium-Catalyzed Coupling of α-Diazo Phosphonates with Benzyl or Allyl Halides.

    PubMed

    Zhou, Yujing; Ye, Fei; Wang, Xi; Xu, Shuai; Zhang, Yan; Wang, Jianbo

    2015-06-19

    An efficient method for the synthesis of organophosphonates through palladium-catalyzed coupling of α-diazo phosphonates with benzyl or allyl halides has been developed. Trisubstituted alkenylphosphonates bearing versatile functional groups can be easily accessed in good yields and with excellent stereoselectivity through this method. Moreover, with similar strategy α-substituted vinylphosphonates can also be attained by the palladium-catalyzed coupling reaction of N-tosylhydrazones and aryl bromides. Migratory insertion of palladium carbene is proposed as the key step in this reaction.

  9. Palladium-catalyzed cross-dehydrogenative functionalization of C(sp(2))-H Bonds.

    PubMed

    Wu, Yinuo; Wang, Jun; Mao, Fei; Kwong, Fuk Yee

    2014-01-01

    The catalytic cross-dehydrogenative coupling (CDC) reaction has received intense attention in recent years. The attractive feature of this coupling process is the formation of a C-C bond from two C-H moieties under oxidative conditions. In this Focus Review, recent advances in the palladium-catalyzed CDC reactions of C(sp(2) )-H bond are summarized, with a focus on the period from 2011 to early 2013. PMID:24123795

  10. Palladium-catalyzed synthesis of N-arylated carbazoles using anilines and cyclic diaryliodonium salts

    PubMed Central

    Riedmüller, Stefan

    2013-01-01

    Summary The direct synthesis of N-arylated carbazoles through a palladium-catalyzed amination of cyclic iodonium salts with anilines is described. In particular, electron-poor aniline derivatives reacted smoothly with only 5 mol % of Pd(OAc)2 as catalyst to give the desired products in up to 71% yield. Furthermore, the reactivity of cyclic iodonium salts is compared with the reactivity of the corresponding cyclic bromonium analogues. PMID:23843915

  11. A Stereoselective Synthesis of Digitoxin and Digitoxigen Monoand Bisdigitoxoside from Digitoxigenin via a Palladium Catalyzed Glycosylation

    PubMed Central

    Zhou, Maoquan; O’Doherty, George A.

    2008-01-01

    A convergent and stereocontrolled route to trisaccharide natural product digitoxin has been developed. The route is amenable to the preparation of both the digitoxigen mono-and bisdigitoxoside. This route featured the iterative application of the palladium catalyzed glycosylation reaction, reductive 1,3-transposition, diastereoselective dihydroxylation and regioselective protection. The natural product digitoxin was fashioned in 15 steps starting from digitoxigenin 2 and pyranone 8a or 18 steps from achiral acylfuran. PMID:16956221

  12. Highly diastereoselective palladium-catalyzed indium-mediated allylation of chiral hydrazones.

    PubMed

    Balasubramanian, Narayanaganesh; Mandal, Tanmay; Cook, Gregory R

    2015-01-16

    The general and efficient palladium-catalyzed indium-mediated allylation of chiral hydrazones was accomplished with excellent yield (72-92%) and diastereoselectivity (up to 99:1). The development of this reaction and the substrate scope are described. The conversion was found to be proportional to the phosphine concentration, which provided insight into the mechanism and competing pathways of the redox transmetalation process.

  13. Palladium-Catalyzed Asymmetric Allylic Alkylations with Toluene Derivatives as Pronucleophiles.

    PubMed

    Mao, Jianyou; Zhang, Jiadi; Jiang, Hui; Bellomo, Ana; Zhang, Mengnan; Gao, Zidong; Dreher, Spencer D; Walsh, Patrick J

    2016-02-12

    The first two highly enantioselective palladium-catalyzed allylic alkylations with benzylic nucleophiles, activated with Cr(CO)3 , have been developed. These methods enable the enantioselective synthesis of α-2-propenyl benzyl motifs, which are important scaffolds in natural products and pharmaceuticals. A variety of cyclic and acyclic allylic carbonates are competent electrophilic partners furnishing the products in excellent enantioselectivity (up to 99 % ee and 92 % yield). This approach was employed to prepare a nonsteroidal anti-inflammatory drug analogue.

  14. Mono- and binuclear cyclometallated palladium(II) complexes containing bridging (N,O-) and terminal (N-) imidate ligands: air stable, thermally robust and recyclable catalysts for cross-coupling processes.

    PubMed

    Fairlamb, Ian J S; Kapdi, Anant R; Lee, Adam F; Sánchez, Gregorio; López, Gregorio; Serrano, José Luis; García, Luis; Pérez, José; Pérez, Eduardo

    2004-12-01

    Novel dinuclear cyclometallated palladium complexes [{Pd(mu-NCO)(C circumflex accent N)}(2)], containing asymmetric imidato -NCO- bridging units have been synthesised [C circumflex accent N = 7,8-benzoquinolyl; -NCO- = succinimidate (1c), phthalimidate (1a-3a) or maleimidate (3c)]. The reaction of these complexes, and the previously reported analogous imidate precursors containing a phenylazophenyl (1a-3a) or 2-pyridylphenyl (1b-3b) backbone, with tertiary phosphines provides novel mononuclear N-bonded imidate derivatives of the general formula [Pd(C circumflex accent N)(imidate)(L)][L = PPh(3), P(4-F-C(6)H(4))(3) or P(4-MeO-C(6)H(4))(3)]. The single crystal structures of [Pd(azb)(phthalimidate)(P(4-MeO-C(6)H(4))(3))](9a) and [Pd(bzq)(phthalimidate)(PPh(3))](7c) have been established. Dinuclear complexes (1a-3a, 1b-3b, 1c-3c) demonstrate outstanding thermal stability in the solid-state, as shown by thermoanalytical techniques. A marked influence of bridging imidate groups on the initial decomposition temperature is observed. The dinuclear and mononuclear derivatives are shown to be active catalysts/precatalysts for the Suzuki-Miyaura cross-coupling reactions of aryl bromides with aryl boronic acids, and the Sonogashira reactions of aryl halides with phenyl acetylene (in the presence and absence of Cu(I) salts). The conversions appear to be dependent, to some extent, on the type of imidate ligand, suggesting a role for these pseudohalides in the catalytic cycle in both cross-coupling processes. Lower catalyst loadings in 'copper-free' Sonogashira cross-couplings favour higher turnover frequencies. We have further determined that these catalysts may be recycled using a poly(ethylene oxide)(PEO)/methanol solvent medium in Suzuki-Miyaura cross-coupling. Once the reaction is complete, product extraction into a hexane/diethyl ether mixture (1 : 1, v/v) gives cross-coupled products in good yields (with purity > 95%). The polar phase can then be re-used several times

  15. Telomerization of amino acids with butadiene, catalyzed by palladium complexes

    SciTech Connect

    Dzhemilev, U.M.; Fakhretdinov, R.N.; Telin, A.G.

    1987-01-10

    The telomerization of ..cap alpha..-, ..beta..-, ..gamma..-, and epsilon-amino acids having various structures with butadiene under the influence of the three-component palladium catalyst Pd(acac)/sub 2/-PPh/sub 3/-AlEt/sub 3/ was investigated in DMSO-toluene solution. The ..cap alpha..- and epsilon-aliphatic and also the ..cap alpha..-, ..beta..-, and ..gamma..-aromatic amino acids react with butadiene, giving the products from octadienylation at the amino group exclusively. Under the conditions of telomerization aliphatic ..beta..-amino acids are cleaved with the formation of unsaturated tertiary amines. In the case of aliphatic ..gamma..-amino acids it is possible to obtain telomers alkylated at the carbonyl group.

  16. Palladium-Catalyzed N-Arylation of 2-Aminothiazoles

    PubMed Central

    McGowan, Meredeth A.; Henderson, Jaclyn L.

    2012-01-01

    A method for the Pd-catalyzed coupling of 2-aminothiazole derivatives with aryl bromides and triflates is described. Significantly, for this class of nucleophiles, the coupling exhibits a broad substrate scope and proceeds with a reasonable catalyst loading. Furthermore, an interesting effect of acetic acid as an additive is uncovered that facilitates catalyst activation. PMID:22394197

  17. Palladium(0)/NHC-Catalyzed Reductive Heck Reaction of Enones: A Detailed Mechanistic Study.

    PubMed

    Raoufmoghaddam, Saeed; Mannathan, Subramaniyan; Minnaard, Adriaan J; de Vries, Johannes G; Reek, Joost N H

    2015-12-14

    We have studied the mechanism of the palladium-catalyzed reductive Heck reaction of para-substituted enones with 4-iodoanisole by using N,N-diisopropylethylamine (DIPEA) as the reductant. Kinetic studies and in situ spectroscopic analysis have provided a detailed insight into the reaction. Progress kinetic analysis demonstrated that neither catalyst decomposition nor product inhibition occurred during the catalysis. The reaction is first order in the palladium and aryl iodide, and zero order in the activated alkene, N-heterocyclic carbene (NHC) ligand, and DIPEA. The experiments with deuterated solvent ([D7]DMF) and deuterated base ([D15]Et3N) supported the role of the amine as a reductant in the reaction. The palladium complex [Pd(0)(NHC)(1)] has been identified as the resting state. The kinetic experiments by stopped-flow UV/Vis also revealed that the presence of the second substrate, benzylideneacetone 1, slows down the oxidative addition of 4-iodoanisole through its competing coordination to the palladium center. The kinetic and mechanistic studies indicated that the oxidative addition of the aryl iodide is the rate-determining step. Various scenarios for the oxidative addition step have been analyzed by using DFT calculations (bp86/def2-TZVP) that supported the inhibiting effect of substrate 1 by formation of resting state [Pd(0)(NHC)(1)] species at the cost of further increase in the energy barrier of the oxidative addition step. PMID:26561034

  18. Palladium-Catalyzed Regioselective Difluoroalkylation and Carbonylation of Alkynes.

    PubMed

    Wang, Qiang; He, Yu-Tao; Zhao, Jia-Hui; Qiu, Yi-Feng; Zheng, Lan; Hu, Jing-Yuan; Yang, Yu-Chen; Liu, Xue-Yuan; Liang, Yong-Min

    2016-06-01

    A novel, four-component synthetic strategy to synthesize a series of β-difluoroalkyl unsaturated esters/amides with high regioslectivity is described. This Pd-catalyzed difluoroalkylation and carbonylation reaction can be carried out with simple starting materials. Through this protocol, two new C-C bonds (including one C-CF2 bond) and one C-O(N) bond are constructed simultaneously in a single step. The synthetic utility of this reaction system has been certified by the applicability to a wide scope of alkynes and nucleophiles. Preliminary mechanistic studies suggest that the difluoroalkyl radical pathway is involved in this reaction. PMID:27191858

  19. Scope of the Palladium-Catalyzed Aryl Borylation Utilizing Bis-Boronic Acid

    PubMed Central

    Molander, Gary A.; Trice, Sarah L. J.; Kennedy, Steven M.; Dreher, Spencer D.; Tudge, Matthew T.

    2012-01-01

    The Suzuki-Miyaura reaction has become one of the more useful tools for synthetic organic chemists. Until recently, there did not exist a direct way to make the most important component in the coupling reaction, namely the boronic acid. Current methods to make boronic acids often employ harsh or wasteful reagents to prepare boronic acid derivatives and require additional steps to afford the desired boronic acid. The scope of the previously reported palladium-catalyzed, direct boronic acid synthesis is unveiled, which includes a wide array of synthetically useful aryl electrophiles. It makes use of the newly available second generation Buchwald XPhos preformed palladium catalyst and bis-boronic acid (BBA). For ease of isolation and to preserve the often sensitive C-B bond, all boronic acids were readily converted to their more stable trifluoroborate counterparts. PMID:22769742

  20. Synthesis of heterocyclic compounds through palladium-catalyzed C-H cyclization processes.

    PubMed

    Inamoto, Kiyofumi

    2013-01-01

    Herein, we describe our development of synthetic methods for heterocyclic compounds based on the palladium-catalyzed carbon-hydrogen bond (C-H) functionalization/intramolecular carbon-heteroatom (nitrogen or sulfur) bond formation process. By this C-H cyclization method, we efficiently prepared various N-heterocycles, including indazoles, indoles, and 2-quinolinones, as well as S-heterocycles such as benzothiazoles and benzo[b]thiophenes. Yields are typically good to high and good functional-group tolerance is observed for each process, thereby indicating that the method provides a novel, highly applicable synthetic route to the abovementioned biologically important heterocyclic frameworks. As an application of this approach, an auto-tandem-type, one-pot process involving the oxidative Heck reaction and subsequent C-H cyclization using cinnamamides and arylboronic acids as starting materials in the presence of a palladium catalyst was also developed for the rapid construction of the 2-quinolinone nucleus. PMID:24088691

  1. Biphasic Palladium-Catalyzed Hydroesterification in a Polyol Phase: Selective Synthesis of Derived Monoesters.

    PubMed

    Pruvost, Romain; Boulanger, Jérôme; Léger, Bastien; Ponchel, Anne; Monflier, Eric; Ibert, Mathias; Mortreux, André; Sauthier, Mathieu

    2015-06-22

    The palladium-catalyzed hydroesterification reaction was performed with polyols and olefins in a liquid/liquid biphasic system composed of unreacted polyol on the one hand and apolar reaction products/organic solvents on the other hand. The palladium-based catalyst was immobilized in the polyol phase thanks to the use of cationic triarylphosphines possessing pendent protonated amino groups in the acidic reaction medium or to the sulfonated phosphine TPPTS (trisodium triphenylphosphine-3,3',3''-trisulfonate). Owing to the insolubility of the products in the catalytic phase, this approach allowed the synthesis of monoesters of polyols with high selectivities as well as the easy separation of the catalyst through simple decantation.

  2. The syn/anti-Dichotomy in the Palladium-Catalyzed Addition of Nucleophiles to Alkenes

    PubMed Central

    Kočovský, Pavel; Bäckvall, Jan-E

    2015-01-01

    In this review the stereochemistry of palladium-catalyzed addition of nucleophiles to alkenes is discussed, and examples of these reactions in organic synthesis are given. Most of the reactions discussed involve oxygen and nitrogen nucleophiles; the Wacker oxidation of ethylene has been reviewed in detail. An anti-hydroxypalladation in the Wacker oxidation has strong support from both experimental and computational studies. From the reviewed material it is clear that anti-addition of oxygen and nitrogen nucleophiles is strongly favored in intermolecular addition to olefin–palladium complexes even if the nucleophile is coordinated to the metal. On the other hand, syn-addition is common in the case of intramolecular oxy- and amidopalladation as a result of the initial coordination of the internal nucleophile to the metal. PMID:25378278

  3. Cross coupling reactions of polyfluoroarenes via C-F activation.

    PubMed

    Sun, Alex D; Love, Jennifer A

    2010-11-21

    This Perspective provides an overview of transition metal-catalyzed cross coupling reactions of polyfluoroarenes. When appropriate, stoichiometric C-F activation and subsequent reaction are briefly covered.

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

    PubMed

    Saadi, Jakub; Bentz, Christoph; Redies, Kai; Lentz, Dieter; Zimmer, Reinhold; Reissig, Hans-Ulrich

    2016-01-01

    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

  5. 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

  6. Palladium-Catalyzed Diastereo- and Enantioselective Formal [3+2]-Cycloadditions of Substituted Vinylcyclopropanes

    PubMed Central

    Trost, Barry M.; Morris, Patrick J.; Sprague, Simon J.

    2012-01-01

    We describe a palladium-catalyzed diastereo- and enantioselective formal [3+2]-cycloaddition between substituted vinyl-cyclopropanes and electron deficient olefins in the form of azlactone- and Meldrum’s acid alkylidenes to give highly-substituted cyclo-pentane products. By modulation of the electronic properties of the vinylcyclopropane and the electron-deficient olefin, high levels of stereoselectivity were obtained. The remote stereoinduction afforded by the catalyst, distal from the chiral pocket generated by the ligand, is proposed to be the result of a new mechanism invoking the Curtin-Hammett principle. PMID:23030714

  7. Switching the Cleavage Sites in Palladium on Carbon-Catalyzed Carbon-Carbon Bond Disconnection.

    PubMed

    Hattori, Tomohiro; Takakura, Ryoya; Ichikawa, Tomohiro; Sawama, Yoshinari; Monguchi, Yasunari; Sajiki, Hironao

    2016-04-01

    We have demonstrated a palladium on carbon-catalyzed approach to regioselectively alter the cleavage sites of the C-C bonds of cinnamaldehyde derivatives by a slight change in the reaction conditions in isopropanol under an O2 atmosphere. Styrene derivatives could be selectively formed by the addition of Na2CO3 in association with the dissociation of carbon monoxide, while benzaldehyde derivatives were generated by the addition of CuCl and morpholine instead of Na2CO3. PMID:26944077

  8. General method for the preparation of active esters by palladium-catalyzed alkoxycarbonylation of aryl bromides.

    PubMed

    de Almeida, Angelina M; Andersen, Thomas L; Lindhardt, Anders T; de Almeida, Mauro V; Skrydstrup, Troels

    2015-02-01

    A useful method was developed for the synthesis of active esters by palladium-catalyzed alkoxycarbonylation of (hetero)aromatic bromides. The protocol was general for a range of oxygen nucleophiles including N-hydroxysuccinimide (NHS), pentafluorophenol (PFP), hexafluoroisopropyl alcohol (HFP), 4-nitrophenol, and N-hydroxyphthalimide. A high functional group tolerance was displayed, and several active esters were prepared with good to excellent isolated yields. The protocol was extended to access an important synthetic precursor to the HIV-protease inhibitor, saquinavir, by formation of an NHS ester followed by acyl substitution.

  9. Palladium-Catalyzed Alkoxycarbonylation of Unactivated Secondary Alkyl Bromides at Low Pressure.

    PubMed

    Sargent, Brendon T; Alexanian, Erik J

    2016-06-22

    Catalytic carbonylations of organohalides are important C-C bond formations in chemical synthesis. Carbonylations of unactivated alkyl halides remain a challenge and currently require the use of alkyl iodides under harsh conditions and high pressures of CO. Herein we report a palladium-catalyzed alkoxycarbonylation of secondary alkyl bromides that proceeds at low pressure (2 atm CO) under mild conditions. Preliminary mechanistic studies are consistent with a hybrid organometallic-radical process. These reactions efficiently deliver esters from unactivated alkyl bromides across a diverse range of substrates and represent the first catalytic carbonylations of alkyl bromides with carbon monoxide.

  10. Palladium-Catalyzed Deaminative Phenanthridinone Synthesis from Aniline via C-H Bond Activation.

    PubMed

    Yedage, Subhash L; Bhanage, Bhalchandra M

    2016-05-20

    This work reports palladium-catalyzed phenanthridinone synthesis using the coupling of aniline and amide by formation of C-C and C-N bonds in a one-pot fashion via dual C-H bond activation. It involves simultaneous cleavage of four bonds and the formation of two new bonds. The present protocol is ligand-free, takes place under mild reaction conditions, and is environmentally benign as nitrogen gas and water are the only side products. This transformation demonstrates a broad range of aniline and amide substrates with different functional groups and has been scaled up to gram level. PMID:27088815

  11. Palladium-Catalyzed Deaminative Phenanthridinone Synthesis from Aniline via C-H Bond Activation.

    PubMed

    Yedage, Subhash L; Bhanage, Bhalchandra M

    2016-05-20

    This work reports palladium-catalyzed phenanthridinone synthesis using the coupling of aniline and amide by formation of C-C and C-N bonds in a one-pot fashion via dual C-H bond activation. It involves simultaneous cleavage of four bonds and the formation of two new bonds. The present protocol is ligand-free, takes place under mild reaction conditions, and is environmentally benign as nitrogen gas and water are the only side products. This transformation demonstrates a broad range of aniline and amide substrates with different functional groups and has been scaled up to gram level.

  12. Assembly of 3-Sulfenylbenzofurans and 3-Sulfenylindoles by Palladium-Catalyzed Cascade Annulation/Arylthiolation Reaction.

    PubMed

    Li, Jianxiao; Li, Chunsheng; Yang, Shaorong; An, Yanni; Wu, Wanqing; Jiang, Huanfeng

    2016-04-01

    A novel and efficient palladium-catalyzed cascade annulation/arylthiolation reaction has been developed to afford functionalized 3-sulfenylbenzofuran and 3-sulfenylindole derivatives in moderate to good yields from readily available 2-alkynylphenols and 2-alkynylamines in ionic liquids. This protocol provides a valuable synthetic tool for the assembly of a wide range of 3-sulfenylbenzofuran and 3-sulfenylindole derivatives with high atom- and step-economy and exceptional functional group tolerance. Moreover, the employment of ionic liquids under mild reaction conditions makes this transformation green and practical. Furthermore, this approach enriched current C-S bond formation chemistry, making a valuable and practical method in synthetic and medicinal chemistry. PMID:26980622

  13. Palladium and platinum catalyzed addition of allylstannanes to aldehydes and imines

    SciTech Connect

    Nakamura, Hiroyuki; Yamamoto, Yoshinori

    1995-12-31

    The reaction of allylstannanes with aldehydes in THF was catalyzed by Pd(II) or Pt(II) complexes (10 mole %) either at room temperature or at reflux, giving the corresponding homoallyl alcohols in high to good yields. Among the catalysts examined, PtCl{sub 2}(PPh{sub 3}){sub 2} gave the best result. Aromatic, aliphatic, and {alpha},{beta}-unsaturated aldehydes can be utilized and even cyclohexanone undergoes the allylation reaction. Allyl and methallyltributylstannane reacted very smoothly. Crotyltributylstannane also reacted with aldehydes to give the branched homoallyl alcohols in good yields, but the reaction speed was slower than that of allylstannane. Detailed mechanistic studies of the Pd(II) catalyzed allylation, using NMR spectra, revealed that bis-{pi}-allyl palladium 5 is a key intermediate for the catalytic cycle and it exhibits nucleophilic reactivity.

  14. Palladium-catalyzed picolinamide-directed iodination of remote ortho-C-H bonds of arenes: Synthesis of tetrahydroquinolines.

    PubMed

    Nack, William A; Wang, Xinmou; Wang, Bo; He, Gang; Chen, Gong

    2016-01-01

    A new palladium-catalyzed picolinamide (PA)-directed ortho-iodination reaction of ε-C(sp(2))-H bonds of γ-arylpropylamine substrates is reported. This reaction proceeds selectively with a variety of γ-arylpropylamines bearing strongly electron-donating or withdrawing substituents, complementing our previously reported PA-directed electrophilic aromatic substitution approach to this transformation. As demonstrated herein, a three step sequence of Pd-catalyzed γ-C(sp(3))-H arylation, Pd-catalyzed ε-C(sp(2))-H iodination, and Cu-catalyzed C-N cyclization enables a streamlined synthesis of tetrahydroquinolines bearing diverse substitution patterns. PMID:27559375

  15. Nickel-Catalyzed Alkyl–Alkyl Cross-Couplings of Fluorinated Secondary Electrophiles: A General Approach to the Synthesis of Compounds that Bear a Perfluoroalkyl Substituent**

    PubMed Central

    Liang, Yufan

    2015-01-01

    Fluorinated organic molecules are of interest in fields ranging from medicinal chemistry to polymer science. Herein, we describe a mild, convenient, and versatile method for the synthesis of compounds that bear a perfluoroalkyl group attached to a tertiary carbon, via an alkyl–alkyl cross-coupling. Thus, a nickel catalyst derived from commercially available components (NiCl2·glyme and a pybox ligand) achieves the coupling of a wide range of fluorinated alkyl halides with alkylzinc reagents at room temperature. A broad array of functional groups (e.g., alkyne, aryl iodide, carbamate, furan, ketone, nitrile, phosphonate, primary alkyl bromide, and primary alkyl tosylate) are compatible with the reaction conditions, and highly selective couplings can be achieved on the basis of differing levels of fluorination. A mechanistic investigation has established that the presence of TEMPO inhibits cross-coupling under these conditions and that a TEMPO–electrophile adduct can be isolated. PMID:26073669

  16. Copper-mediated and copper-catalyzed cross-coupling of indoles and 1,3-azoles: double C-H activation.

    PubMed

    Nishino, Mayuko; Hirano, Koji; Satoh, Tetsuya; Miura, Masahiro

    2012-07-01

    A new bronze age: the described copper-mediated cross-coupling with double C-H activation can provide a convergent access to indole-containing biheteroaryls that are of high interest in pharmaceutical and medicinal chemistry. In this strategy an easily attachable and detachable 2-pyrimidyl directing group is used. Moreover, a variant that is catalytic in copper is achieved by using atmospheric oxygen as an ideal co-oxidant.

  17. Palladium-catalyzed regioselective intramolecular coupling of o-carborane with aromatics via direct cage B-H activation.

    PubMed

    Quan, Yangjian; Xie, Zuowei

    2015-03-18

    Palladium-catalyzed intramolecular coupling of o-carborane with aromatics via direct cage B-H bond activation has been achieved, leading to the synthesis of a series of o-carborane-functionalized aromatics in high yields with excellent regioselectivity. In addition, the site selectivity can also be tuned by the substituents on cage carbon atom.

  18. Kinetic resolution of axially chiral 2,2'-dihydroxy-1,1'-biaryls by palladium-catalyzed alcoholysis.

    PubMed

    Aoyama, Hiroshi; Tokunaga, Makoto; Kiyosu, Junya; Iwasawa, Tetsuo; Obora, Yasushi; Tsuji, Yasushi

    2005-08-01

    Palladium-diamine complexes catalyzed kinetic resolution of axially chiral 2,2'-dihydroxy-1,1'-biaryls by alcoholysis of vinyl ethers. The reaction proceeded with high selectivity for various kinds of biaryls. This process is applicable to not only binaphthols but also biphenols, which have been considered to be difficult for the enantioselective synthesis by known catalytic methods. PMID:16045319

  19. Enantioselective synthesis of 4-substituted tetrahydroisoquinolines via palladium-catalyzed intramolecular Friedel-Crafts type allylic alkylation of phenols.

    PubMed

    Zhao, Zheng-Le; Xu, Qing-Long; Gu, Qing; Wu, Xin-Yan; You, Shu-Li

    2015-03-14

    Palladium-catalyzed asymmetric intramolecular Friedel-Crafts type allylic alkylation reaction of phenols was developed under mild conditions. In the presence of Pd2(dba)3 with (1R,2R)-DACH-phenyl Trost ligand (L2) in toluene at 50 °C, the reaction provides various C4 substituted tetrahydroisoquinolines with moderate to excellent yields, regioselectivity and enantioselectivity. PMID:25625805

  20. A general synthesis of fluoroalkylated alkenes by palladium-catalyzed Heck-type reaction of fluoroalkyl bromides.

    PubMed

    Feng, Zhang; Min, Qiao-Qiao; Zhao, Hai-Yang; Gu, Ji-Wei; Zhang, Xingang

    2015-01-19

    An efficient palladium-catalyzed Heck-type reaction of fluoroalkyl halides, including perfluoroalkyl bromides, trifluoromethyl iodides, and difluoroalkyl bromides, has been developed. The reaction proceeds under mild reaction conditions with high efficiency and broad substrate scope, and provides a general and straightforward access to fluoroalkylated alkenes which are of interest in life and material sciences.

  1. Development of Chiral Bis-hydrazone Ligands for the Enantioselective Cross-Coupling Reactions of Aryldimethylsilanolates

    PubMed Central

    2015-01-01

    A palladium-catalyzed, enantioselective, aryl–aryl cross-coupling reaction using 1-naphthyldimethylsilanolates and chiral bis-hydrazone ligands has been developed. A family of glyoxal bis-hydrazone ligands containing various 2,5-diarylpyrrolidine groups was prepared to evaluate the influence of ligand structure on the rate and enantioselectivity of the cross-coupling. New synthetic routes to the 1-amino-2,5-diarylpyrrolidines were developed to enable the structure/reactivity–selectivity studies. Role reversal experiments of aryldimethylsilanolates and aryl bromides result in biaryl products with the same configuration and similar enantioselectivities implying that reductive elimination is the stereodetermining step. The origin of stereoselectivity is rationalized through computational modeling of diarylpalldium(II) complex which occurs through a conrotatory motion for the two aryl groups undergoing C–C bond formation. PMID:25494058

  2. Palladium-catalyzed through-space C(sp(3))-H and C(sp(2))-H bond activation by 1,4-palladium migration: efficient synthesis of [3,4]-fused oxindoles.

    PubMed

    Piou, Tiffany; Bunescu, Ala; Wang, Qian; Neuville, Luc; Zhu, Jieping

    2013-11-18

    Palladium two step: Linear anilides were converted into the title compounds in good to excellent yields through a palladium-catalyzed domino carbopalladation/1,4-palladium shift sequence. The C(sp(3) )-H activation involves a seven-membered palladacycle, and is chemoselective in the presence of competitive C(sp(2) )H bonds. DMA=N,N-dimethylacetamide, OPiv=pivalate.

  3. 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

  4. 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

  5. Mechanistic insights on platinum- and palladium-pincer catalyzed coupling and cyclopropanation reactions between olefins.

    PubMed

    Rajeev, Ramanan; Sunoj, Raghavan B

    2012-07-21

    The mechanism of M(II)-PNP-pincer catalyzed reaction between (i) ethene, (ii) trans-butene with 2-methylbut-2-ene, 2,3-dimethylbut-2-ene and tert-butylbutene is examined by using density functional theory methods (where M = Pt or Pd). All key intermediates and transition states involved in the reaction are precisely located on the respective potential energy surfaces using the popular DFT functionals such as mPW1K, M06-2X, and B3LYP in conjunction with the 6-31+G** basis set. The reaction between these olefins can lead to a linear coupling product or a substituted cyclopropane. The energetic comparison between coupling as well as cyclopropanation pathways involving four pairs of olefins for both platinum (1-4) and palladium (5-8) catalyzed reactions is performed. The key events in the lower energy pathway in the mechanistic course involves (i) a C-C bond formation between the metal bound olefin (ethene or trans-butene) and a free olefin, and (ii) two successive [1,2] hydrogen migrations in the ensuing carbocationic intermediates (1c-4c, and 1d-4d), toward the formation of the coupling product. The computed barriers for these steps in the reaction of metal bound ethene to free tert-butylbutene (or other butenes) are found to be much lower than the corresponding steps when trans-butene is bound to the metal pincer. The Gibbs free energy differences between the transition states leading to the coupling product (TS(d-e)) and that responsible for cyclopropanated product (TS(d-g)) are found to be diminishingly closer in the case of the platinum pincer as compared to that in the palladium system. The computed energetics indicate that the coupled product prefers to remain as a metal olefin complex, consistent with the earlier experimental reports.

  6. Nickel-catalyzed cross-coupling of phenols and arylboronic acids through an in situ phenol activation mediated by PyBroP.

    PubMed

    Chen, Guo-Jun; Huang, Jie; Gao, Lian-Xun; Han, Fu-She

    2011-03-28

    A new method for the Suzuki-Miyaura cross-coupling of phenols and arylboronic acids through in situ phenol activation mediated by PyBroP is presented. The reaction proceeds efficiently by using cost-effective, markedly stable [NiCl(2)(dppp)] (dppp=1,3-bis(diphenylphosphino)propane) as the catalyst in only 5 mol % loading, as well as in the absence of extra ligands. The method exhibits broad applicability and high efficiency towards a wide range of both phenols and boronic acids, including activated, nonactivated, deactivated, and heteroaromatic coupling partners. In addition, various functional groups, such as ether, amino, cyano, ester, and ketone groups, are compatible with this transformation. Notably, arylboronic acids containing an unprotected NH(2) group and 2-heterocyclic boronic acids, which are generally problematic for coupling under conventional conditions, are also viable substrates, although moderate yields were obtained for sterically hindered substrates. Consequently, the in situ cross-coupling methodology coupled with the use of an inexpensive and stable nickel catalyst provides a rapid and efficient pathway for the assembly of biaryls and heterobiaryls with structural diversity from readily available phenol compounds.

  7. A tandem Mannich addition–palladium catalyzed ring-closing route toward 4-substituted-3(2H)-furanones

    PubMed Central

    John, Jubi; Târcoveanu, Eliza; Jones, Peter G

    2014-01-01

    Summary A facile route towards highly functionalized 3(2H)-furanones via a sequential Mannich addition–palladium catalyzed ring closing has been elaborated. The reaction of 4-chloroacetoacetate esters with imines derived from aliphatic and aromatic aldehydes under palladium catalysis afforded 4-substituted furanones in good to excellent yields. 4-Hydrazino-3(2H)-furanones could also be synthesized from diazo esters in excellent yields by utilising the developed strategy. We could also efficiently transform the substituted furanones to aza-prostaglandin analogues. PMID:24991301

  8. Palladium-Catalyzed Defluorinative Coupling of 1-Aryl-2,2-Difluoroalkenes and Boronic Acids: Stereoselective Synthesis of Monofluorostilbenes.

    PubMed

    Thornbury, Richard T; Toste, F Dean

    2016-09-12

    The palladium-catalyzed defluorinative coupling of 1-aryl-2,2-difluoroalkenes with boronic acids is described. Broad functional-group tolerance arises from a redox-neutral process by a palladium(II) active species which is proposed to undergo a β-fluoride elimination to afford the products. The monofluorostilbene products were formed with excellent diastereoselectivity (≥50:1) in all cases, and it is critical, as traditional chromatographic techniques often fail to separate monofluoroalkene isomers. As a demonstration of this method's unique combination of reactivity and functional-group tolerance, a Gleevec® analogue, using a monofluorostilbene as an amide isostere, was synthesized. PMID:27511868

  9. 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

  10. Palladium-atom catalyzed formic acid decomposition and the switch of reaction mechanism with temperature.

    PubMed

    He, Nan; Li, Zhen Hua

    2016-04-21

    Formic acid decomposition (FAD) reaction has been an innovative way for hydrogen energy. Noble metal catalysts, especially palladium-containing nanoparticles, supported or unsupported, perform well in this reaction. Herein, we considered the simplest model, wherein one Pd atom is used as the FAD catalyst. With high-level theoretical calculations of CCSD(T)/CBS quality, we investigated all possible FAD pathways. The results show that FAD catalyzed by one Pd atom follows a different mechanism compared with that catalyzed by surfaces or larger clusters. At the initial stage of the reaction, FAD follows a dehydration route and is quickly poisoned by CO due to the formation of very stable PdCO. PdCO then becomes the actual catalyst for FAD at temperatures approximately below 1050 K. Beyond 1050 K, there is a switch of catalyst from PdCO to Pd atom. The results also show that dehydration is always favoured over dehydrogenation on either the Pd-atom or PdCO catalyst. On the Pd-atom catalyst, neither dehydrogenation nor dehydration follows the formate mechanism. In contrast, on the PdCO catalyst, dehydrogenation follows the formate mechanism, whereas dehydration does not. We also systematically investigated the performance of 24 density functional theory methods. We found that the performance of the double hybrid mPW2PLYP functional is the best, followed by the B3LYP, B3PW91, N12SX, M11, and B2PLYP functionals.

  11. Palladium-atom catalyzed formic acid decomposition and the switch of reaction mechanism with temperature.

    PubMed

    He, Nan; Li, Zhen Hua

    2016-04-21

    Formic acid decomposition (FAD) reaction has been an innovative way for hydrogen energy. Noble metal catalysts, especially palladium-containing nanoparticles, supported or unsupported, perform well in this reaction. Herein, we considered the simplest model, wherein one Pd atom is used as the FAD catalyst. With high-level theoretical calculations of CCSD(T)/CBS quality, we investigated all possible FAD pathways. The results show that FAD catalyzed by one Pd atom follows a different mechanism compared with that catalyzed by surfaces or larger clusters. At the initial stage of the reaction, FAD follows a dehydration route and is quickly poisoned by CO due to the formation of very stable PdCO. PdCO then becomes the actual catalyst for FAD at temperatures approximately below 1050 K. Beyond 1050 K, there is a switch of catalyst from PdCO to Pd atom. The results also show that dehydration is always favoured over dehydrogenation on either the Pd-atom or PdCO catalyst. On the Pd-atom catalyst, neither dehydrogenation nor dehydration follows the formate mechanism. In contrast, on the PdCO catalyst, dehydrogenation follows the formate mechanism, whereas dehydration does not. We also systematically investigated the performance of 24 density functional theory methods. We found that the performance of the double hybrid mPW2PLYP functional is the best, followed by the B3LYP, B3PW91, N12SX, M11, and B2PLYP functionals. PMID:27005983

  12. Carbon-carbon cross-coupling reactions catalyzed by a two-coordinate nickel(II)-bis(amido) complex via observable Ni(I) , Ni(II) , and Ni(III) intermediates.

    PubMed

    Lipschutz, Michael I; Tilley, T Don

    2014-07-01

    Recently, the development of more sustainable catalytic systems based on abundant first-row metals, especially nickel, for cross-coupling reactions has attracted significant interest. One of the key intermediates invoked in these reactions is a Ni(III) -alkyl species, but no such species that is part of a competent catalytic cycle has yet been isolated. Herein, we report a carbon-carbon cross-coupling system based on a two-coordinate Ni(II) -bis(amido) complex in which a Ni(III) -alkyl species can be isolated and fully characterized. This study details compelling experimental evidence of the role played by this Ni(III) -alkyl species as well as those of other key Ni(I) and Ni(II) intermediates. The catalytic cycle described herein is also one of the first examples of a two-coordinate complex that competently catalyzes an organic transformation, potentially leading to a new class of catalysts based on the unique ability of first-row transition metals to accommodate two-coordinate complexes.

  13. Short Synthesis of Sulfur Analogues of Polyaromatic Hydrocarbons through Three Palladium-Catalyzed C-H Bond Arylations.

    PubMed

    Hagui, Wided; Besbes, Néji; Srasra, Ezzeddine; Roisnel, Thierry; Soulé, Jean-François; Doucet, Henri

    2016-09-01

    An expeditious synthesis of a wide range of phenanthro[9,10-b]thiophene derivatives, which are a class of polyaromatic hydrocarbon (PAH) containing a sulfur atom, is reported. The synthetic scheme involves only two operations from commercially available thiophenes, 2-bromobenzenesulfonyl chlorides and aryl bromides. In the first step, palladium-catalyzed desulfitative arylation using 2-bromobenzenesulfonyl chlorides allows the synthesis of thiophene derivatives, which are substituted at the C4 position by an aryl group containing an ortho-bromo substituent. Then, a palladium-catalyzed one-pot cascade intermolecular C5-arylation of thiophene using aryl bromides followed by intramolecular arylation led to the corresponding phenanthro[9,10-b]thiophenes in a single operation. In addition, PAHs containing two or three sulfur atoms, as well as both sulfur and nitrogen atoms, were also designed by this strategy. PMID:27550151

  14. Cu-catalyzed Fe-driven C(sp)-C(sp) and C(s)p-C(sp2) cross-coupling: an access to 1,3-diynes and 1,3-enynes.

    PubMed

    Ahammed, Sabir; Kundu, Debasish; Ranu, Brindaban C

    2014-08-15

    An efficient Csp-Csp cross-coupling of alkynyl bromide and pinacol ester of alkynyl boronic acid catalyzed by CuFe2O4 nanoparticles has been accomplished in dimethyl carbonate to produce unsymmetric 1,3-diynes. This protocol is also extended for the Csp-Csp2 coupling of alkynyl bromide and alkenyl boronic acid to provide conjugated 1,3-enynes. The aliphatic, aromatic, and heteroaromatic alkynes couple with various substituted alkynyl/alkenyl boronates/boronic acids by this procedure to furnish a library of 1,3-diynes and enynes in high yields. The catalyst was easily separated by an external magnet and recycled 10 times. PMID:25046329

  15. Synthesis of chiral biphenol-based diphosphonite ligands and their application in palladium-catalyzed intermolecular asymmetric allylic amination reactions.

    PubMed

    Shi, Ce; Chien, Chih-Wei; Ojima, Iwao

    2011-02-01

    A library of new 2,2'-bis(diphenylphosphinoyloxy)-1,1'-binaphthyl (binapo)-type chiral diphosphonite ligands was designed and synthesized based on chiral 3,3',5,5',6,6'-hexasubstituted biphenols. These bop ligands have exhibited excellent efficiency in a palladium-catalyzed intermolecular allylic amination reaction, which provides a key intermediate for the total synthesis of Strychnos indole alkaloids with enantiopurities of up to 96% ee. PMID:21254441

  16. A general and practical palladium-catalyzed monoarylation of β-methyl C(sp³)-H of alanine.

    PubMed

    Chen, Kai; Zhang, Shuo-Qing; Xu, Jing-Wen; Hu, Fang; Shi, Bing-Feng

    2014-11-21

    A palladium-catalyzed monoarylation of β-methyl C(sp(3))-H of an alanine derivative with aryl iodides using an 8-aminoquinoline auxiliary is described. The reaction is highly efficient, scalable and compatible with a variety of functional groups with complete retention of chirality, providing a general and practical access to various β-aryl-α-amino acids. The synthetic potential of this protocol is further demonstrated in the sequential synthesis of diverse β-branched α-amino acids.

  17. Aerobic palladium(II)-catalyzed dehydrogenation of cyclohexene-1-carbonyl indole amides: an indole-directed aromatization.

    PubMed

    Kandukuri, Sandeep R; Oestreich, Martin

    2012-10-01

    A palladium(II)-catalyzed oxidative dehydrogenation of cyclohexene-1-carbonyl indole amides yielding the corresponding benzoylindoles is reported. The new aromatization is also applied to functionalized indoles such as tryptamine and tryptophan. The tethered indole is likely acting as a directing group for allylic C-H bond activation, and there is evidence for a mechanism proceeding through 1,3-diene formation followed by aromatization. PMID:22950832

  18. Palladium-Catalyzed Benzylic Arylation of Pyridylmethyl Silyl Ethers: One-Pot Synthesis of Aryl(pyridyl)methanols.

    PubMed

    Rivero, Alexandra R; Kim, Byeong-Seon; Walsh, Patrick J

    2016-04-01

    An efficient palladium-catalyzed direct arylation of pyridylmethyl silyl ethers with aryl bromides is described. A Pd(OAc)2/NIXANTPHOS-based catalyst provides aryl(pyridyl)methyl alcohol derivatives in good to excellent yields (33 examples, 57-100% yield). This protocol is compatible with different silyl ether protecting groups, affording either the protected or the free alcohols in an effective one-pot process. The scalability of the reaction is demonstrated. PMID:27004592

  19. A stereoselective synthesis of digitoxin and digitoxigen mono- and bisdigitoxoside from digitoxigenin via a palladium-catalyzed glycosylation.

    PubMed

    Zhou, Maoquan; O'Doherty, George A

    2006-09-14

    A convergent and stereocontrolled route to trisaccharide natural product digitoxin has been developed. The route is amenable to the preparation of both the digitoxigen mono- and bisdigitoxoside. This route featured the iterative application of the palladium-catalyzed glycosylation reaction, reductive 1,3-transposition, diastereoselective dihydroxylation, and regioselective protection. The natural product digitoxin was fashioned in 15 steps starting from digitoxigenin 2 and pyranone 8a or 18 steps from achiral acylfuran. PMID:16956221

  20. Palladium-Catalyzed Intramolecular C–H Difluoroalkyation: The Synthesis of Substituted 3,3-Difluoro-2-oxindoles**

    PubMed Central

    Shi, Shi-Liang

    2015-01-01

    The synthesis of 3,3-difluoro-2-oxindoles through a robust and efficient palladium-catalyzed C–H difluoroalkylation is described. This process generates a broad range of difluorooxindoles from readily prepared starting materials. The use of BrettPhos as the ligand was crucial for high efficiency. Preliminary mechanistic studies suggest that oxidative addition is the rate-determining step for this process. PMID:25476241

  1. Access to 4-alkylaminopyridazine derivatives via nitrogen-assisted regioselective Pd-catalyzed reactions.

    PubMed

    Blaise, Emilie; Kümmerle, Arthur E; Hammoud, Hassan; de Araújo-Júnior, João Xavier; Bihel, Frédéric; Bourguignon, Jean-Jacques; Schmitt, Martine

    2014-11-01

    3-Substituted, 6-substituted, and unsymmetrical 3,6-disubstituted 4-alkylaminopyridazines were prepared from a sequence of three chemo- and regioselective reactions combining amination and palladium-catalyzed cross-coupling reactions, such as reductive dehalogenation and Suzuki-Miyaura reactions. Extension of the methodology to Sonogashira reaction yielded a novel class of 3-substituted pyrrolopyridazines. PMID:25310174

  2. Reactions of organometallic compounds catalyzed by transition metal complexes. XIII. Comparison of the reactivity of organometallic compounds in aryldemetallation reactions catalyzed by palladium complexes

    SciTech Connect

    Bumagin, N.A.; Ponomarev, A.B.; Beletskaya, I.P.

    1987-12-10

    The effect of the nature of the metal M and the organic group R on the reaction of organometallic compounds RM (R = Ph, PhC triple bond C, C/sub 3/H/sub 7/, Allyl; M = Li, Mg, Zn, Cd, Cu Al), produced in situ from Grignard reagents or organolithium compounds and the respective salts, with p-iodoanisole in the presence of palladium complexes PdCl/sub 2/L/sub 2/ (L = PPh/sub 3/, MeCN, dppf) was studied. The organozinc and organoaluminum compounds react with a high degree of selectivity. In the reactions of C/sub 3/H/sub 7/M with p-MeOC/sub 6/H/sub 4/I the highest yield from cross-coupling is obtained with catalysis by the PdCl/sub 2/ (dppf) complex. The mechanism of the formation of the homocoupling products is discussed.

  3. Catalytic conjunctive cross-coupling enabled by metal-induced metallate rearrangement.

    PubMed

    Zhang, Liang; Lovinger, Gabriel J; Edelstein, Emma K; Szymaniak, Adam A; Chierchia, Matteo P; Morken, James P

    2016-01-01

    Transition metal catalysis plays a central role in contemporary organic synthesis. Considering the tremendously broad array of transition metal-catalyzed transformations, it is remarkable that the underlying elementary reaction steps are relatively few in number. Here, we describe an alternative to the organometallic transmetallation step that is common in many metal-catalyzed reactions, such as Suzuki-Miyaura coupling. Specifically, we demonstrate that vinyl boronic ester ate complexes, prepared by combining organoboronates and organolithium reagents, engage in palladium-induced metallate rearrangement wherein 1,2-migration of an alkyl or aryl group from boron to the vinyl α-carbon occurs concomitantly with C-Pd σ-bond formation. This elementary reaction enables a powerful cross-coupling reaction in which a chiral Pd catalyst merges three simple starting materials-an organolithium, an organoboronic ester, and an organotriflate-into chiral organoboronic esters with high enantioselectivity.

  4. Palladium-catalyzed picolinamide-directed iodination of remote ortho-C−H bonds of arenes: Synthesis of tetrahydroquinolines

    PubMed Central

    Nack, William A; Wang, Xinmou; Wang, Bo

    2016-01-01

    Summary A new palladium-catalyzed picolinamide (PA)-directed ortho-iodination reaction of ε-C(sp2)−H bonds of γ-arylpropylamine substrates is reported. This reaction proceeds selectively with a variety of γ-arylpropylamines bearing strongly electron-donating or withdrawing substituents, complementing our previously reported PA-directed electrophilic aromatic substitution approach to this transformation. As demonstrated herein, a three step sequence of Pd-catalyzed γ-C(sp3)−H arylation, Pd-catalyzed ε-C(sp2)−H iodination, and Cu-catalyzed C−N cyclization enables a streamlined synthesis of tetrahydroquinolines bearing diverse substitution patterns. PMID:27559375

  5. Copper-catalyzed/promoted cross-coupling of gem-diborylalkanes with nonactivated primary alkyl halides: an alternative route to alkylboronic esters.

    PubMed

    Zhang, Zhen-Qi; Yang, Chu-Ting; Liang, Lu-Jun; Xiao, Bin; Lu, Xi; Liu, Jing-Hui; Sun, Yan-Yan; Marder, Todd B; Fu, Yao

    2014-12-19

    The first copper-catalyzed/promoted sp(3)-C Suzuki-Miyaura coupling reaction of gem-diborylalkanes with nonactivated electrophilic reagents is reported. Not only 1, 1-diborylalkanes but also some other gem-diborylalkanes can be coupled with nonactivated primary alkyl halides, offering a new method for sp(3)C-sp(3)C bond formation and, simultaneously, providing a new strategy for the synthesis of alkylboronic esters. PMID:25436511

  6. Transition metal-catalyzed functionalization of pyrazines.

    PubMed

    Nikishkin, Nicolai I; Huskens, Jurriaan; Verboom, Willem

    2013-06-14

    Transition metal-catalyzed reactions are generally used for carbon-carbon bond formation on pyrazines and include, but are not limited to, classical palladium-catalyzed reactions like Sonogashira, Heck, Suzuki, and Stille reactions. Also a few examples of carbon-heteroatom bond formation in pyrazines are known. This perspective reviews recent progress in the field of transition metal-catalyzed cross-coupling reactions on pyrazine systems. It deals with the most important C-C- and C-X-bond formation methodologies.

  7. Catalysis in the Service of Green Chemistry: Nobel Prize-Winning Palladium-Catalysed Cross-Couplings, Run in Water at Room Temperature: Heck, Suzuki-Miyaura and Negishi reactions carried out in the absence of organic solvents, enabled by micellar catalysis.

    PubMed

    Lipshutz, Bruce H; Taft, Benjamin R; Abela, Alexander R; Ghorai, Subir; Krasovskiy, Arkady; Duplais, Christophe

    2012-04-01

    Palladium-catalysed cross-couplings, in particular Heck, Suzuki-Miyaura and Negishi reactions developed over three decades ago, are routinely carried out in organic solvents. However, alternative media are currently of considerable interest given an increasing emphasis on making organic processes 'greener'; for example, by minimising organic waste in the form of organic solvents. Water is the obvious leading candidate in this regard. Hence, this review focuses on the application of micellar catalysis, in which a 'designer' surfactant enables these award-winning coupling reactions to be run in water at room temperature. PMID:23555153

  8. Catalysis in the Service of Green Chemistry: Nobel Prize-Winning Palladium-Catalysed Cross-Couplings, Run in Water at Room Temperature: Heck, Suzuki-Miyaura and Negishi reactions carried out in the absence of organic solvents, enabled by micellar catalysis.

    PubMed

    Lipshutz, Bruce H; Taft, Benjamin R; Abela, Alexander R; Ghorai, Subir; Krasovskiy, Arkady; Duplais, Christophe

    2012-04-01

    Palladium-catalysed cross-couplings, in particular Heck, Suzuki-Miyaura and Negishi reactions developed over three decades ago, are routinely carried out in organic solvents. However, alternative media are currently of considerable interest given an increasing emphasis on making organic processes 'greener'; for example, by minimising organic waste in the form of organic solvents. Water is the obvious leading candidate in this regard. Hence, this review focuses on the application of micellar catalysis, in which a 'designer' surfactant enables these award-winning coupling reactions to be run in water at room temperature.

  9. 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.

  10. Oxidative Cross-Coupling of sp(3)- and sp(2)-Hybridized C-H Bonds: Vanadium-Catalyzed Aminomethylation of Imidazo[1,2-a]pyridines.

    PubMed

    Kaswan, Pinku; Porter, Ashley; Pericherla, Kasiviswanadharaju; Simone, Marissa; Peters, Sean; Kumar, Anil; DeBoef, Brenton

    2015-11-01

    The vanadium-catalyzed oxidative coupling of substituted 2-arylimidiazo[1,2-a]pyridines to N-methylmorpholine oxide, which acts as both a coupling partner and an oxidant, has been achieved. This reaction was applied to various substituted imidiazo[1,2-a]pyridine and indole substrates, resulting in yields as high as 90%. Mechanistic investigations indicate that the reaction may proceed via a Mannich-type process. This work demonstrates how oxidative aminomethylation can be used as a useful method to introduce tertiary amines into heterocycles, thus providing an alternative method for conventional Mannich-type reactions.

  11. 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

  12. Palladium-Based Nanomaterials: A Platform to Produce Reactive Oxygen Species for Catalyzing Oxidation Reactions.

    PubMed

    Long, Ran; Huang, Hao; Li, Yaping; Song, Li; Xiong, Yujie

    2015-11-25

    Oxidation reactions by molecular oxygen (O2 ) over palladium (Pd)-based nanomaterials are a series of processes crucial to the synthesis of fine chemicals. In the past decades, investigations of related catalytic materials have mainly been focused on the synthesis of Pd-based nanomaterials from the angle of tailoring their surface structures, compositions and supporting materials, in efforts to improve their activities in organic reactions. From the perspective of rational materials design, it is imperative to address the fundamental issues associated with catalyst performance, one of which should be oxygen activation by Pd-based nanomaterials. Here, the fundamentals that account for the transformation from O2 to reactive oxygen species over Pd, with a focus on singlet O2 and its analogue, are introduced. Methods for detecting and differentiating species are also presented to facilitate future fundamental research. Key factors for tuning the oxygen activation efficiencies of catalytic materials are then outlined, and recent developments in Pd-catalyzed oxygen-related organic reactions are summarized in alignment with each key factor. To close, we discuss the challenges and opportunities for photocatalysis research at this unique intersection as well as the potential impact on other research fields.

  13. Palladium-Catalyzed Transannular C–H Functionalization of Alicyclic Amines

    PubMed Central

    Saper, Noam I.; Sanford, Melanie S.

    2016-01-01

    The discovery of pharmaceutical candidates is a resource-intensive enterprise that frequently requires the parallel synthesis of hundreds or even thousands of molecules. Carbon-hydrogen bonds are present in almost all pharmaceutical agents. As such, the development of selective, rapid, and efficient methods for converting carbon-hydrogen bonds into new chemical entities has the potential to dramatically streamline pharmaceutical development1,2,3,4. Saturated nitrogen-containing heterocycles (alicyclic amines) feature prominently in pharmaceuticals, including treatments for depression (paroxetine, amitifadine), diabetes (gliclazide), leukemia (alvocidib), schizophrenia (risperidone, belaperidone), and nicotine addiction (cytisine and varenicline)5. However, existing methods for the C–H functionalization of saturated nitrogen heterocycles, particularly at sites remote to nitrogen, remain extremely limited 6,7. Here we report a new approach to selectively manipulate the carbon–hydrogen bonds of alicyclic amines at sites remote to nitrogen. Our reaction leverages the boat conformation of the substrates to achieve the palladium-catalyzed amine-directed conversion of C–H bonds to C–C bonds on various alicyclic amine scaffolds. This approach is applied to the synthesis of novel derivatives of several bioactive molecules, including the top-selling smoking cessation drug varenicline (Chantix®). We anticipate that this method should prove broadly useful in medicinal chemistry. PMID:26886789

  14. Palladium-Based Nanomaterials: A Platform to Produce Reactive Oxygen Species for Catalyzing Oxidation Reactions.

    PubMed

    Long, Ran; Huang, Hao; Li, Yaping; Song, Li; Xiong, Yujie

    2015-11-25

    Oxidation reactions by molecular oxygen (O2 ) over palladium (Pd)-based nanomaterials are a series of processes crucial to the synthesis of fine chemicals. In the past decades, investigations of related catalytic materials have mainly been focused on the synthesis of Pd-based nanomaterials from the angle of tailoring their surface structures, compositions and supporting materials, in efforts to improve their activities in organic reactions. From the perspective of rational materials design, it is imperative to address the fundamental issues associated with catalyst performance, one of which should be oxygen activation by Pd-based nanomaterials. Here, the fundamentals that account for the transformation from O2 to reactive oxygen species over Pd, with a focus on singlet O2 and its analogue, are introduced. Methods for detecting and differentiating species are also presented to facilitate future fundamental research. Key factors for tuning the oxygen activation efficiencies of catalytic materials are then outlined, and recent developments in Pd-catalyzed oxygen-related organic reactions are summarized in alignment with each key factor. To close, we discuss the challenges and opportunities for photocatalysis research at this unique intersection as well as the potential impact on other research fields. PMID:26422795

  15. Palladium-Catalyzed 1,3-Difunctionalization Using Terminal Alkenes with Alkenyl Nonaflates and Aryl Boronic Acids.

    PubMed

    McCammant, Matthew S; Shigeta, Takashi; Sigman, Matthew S

    2016-04-15

    A Pd-catalyzed 1,3-difunctionalization of terminal alkenes using 1,1-disubstituted alkenyl nonaflates and arylboronic acid coupling partners is reported. This transformation affords allylic arene products that are difficult to selectively access using traditional Heck cross-coupling methodologies. The evaluation of seldom employed 1,1-disubstituted alkenyl nonaflate coupling partners led to the elucidation of subtle mechanistic features of π-allyl stabilized Pd-intermediates. Good stereo- and regioselectivity for the formation of 1,3-addition products can be accessed through a minimization of steric interactions that emanate from alkenyl nonaflate substitution.

  16. Efficient and General Aerobic Oxidative Cross-Coupling of THIQs with Organozinc Reagents Catalyzed by CuCl2: Proof of a Radical Intermediate.

    PubMed

    Wang, Tongtong; Schrempp, Michael; Berndhäuser, Andreas; Schiemann, Olav; Menche, Dirk

    2015-08-21

    A general new method for the highly concise synthesis of C-1-alkylated tetrahydroisoquinolines (THIQ) is reported. The CuCl2-catalyzed procedure is based on a coupling of nonfunctionalized THIQs with organozinc reagents under aerobic conditions. It proceeds in high yields and is broadly applicable to a wide range of substrates. It relies on a regioselective sp(3) C-H bond activation allowing for an sp(3)-sp(3) bond union under mild reaction conditions in a rapid and effective manner. Mechanistically it involves an iminium ion intermediate that is formed via an organic radical involving a single-electron-transfer process. For the first time for this type of reaction a radical intermediate has been proven by EPR spectroscopy. PMID:26252357

  17. Palladium-catalyzed Allylic Substitution with (η6-arene–CH2Z)Cr(CO)3-based Nucleophiles

    PubMed Central

    Zhang, Jiadi; Stanciu, Corneliu; Wang, Beibei; Hussain, Mahmud M.; Da, Chao-Shan; Carroll, Patrick J.; Dreher, Spencer D.; Walsh, Patrick J.

    2011-01-01

    Although the palladium-catalyzed Tsuji-Trost allylic substitution reaction has been intensively studied, there is a lack of general methods to employ simple benzylic nucleophiles. Such a method would facilitate access to “α-2-propenyl benzyl” motifs, which are common structural motifs in bioactive compounds and natural products. We report herein the palladium-catalyzed allylation reaction of toluene-derived pronucleophiles activated by tricarbonylchromium. A variety of cyclic and acyclic allylic electrophiles can be employed with in situ generated (η6-C6H5–CHLiR)Cr(CO)3 nucleophiles. Catalyst identification was performed by high throughput experimentation (HTE) and led to the Xantphos/palladium hit, which proved to be a general catalyst for this class of reactions. In addition to η6-toluene complexes, benzyl amine and ether derivatives (η6-C6H5–CH2Z)Cr(CO)3 (Z=NR2, OR) are also viable pronucleophiles, allowing C–C bond-formation alpha to heteroatoms with excellent yields. Finally, a tandem allylic substitution/demetallation procedure is described that affords the corresponding metal-free allylic substitution products. This method will be a valuable complement to the existing arsenal of nucleophiles with applications in allylic substitution reactions. PMID:22047504

  18. Palladium-catalyzed mono-N-allylation of unprotected anthranilic acids with allylic alcohols in aqueous media.

    PubMed

    Hikawa, Hidemasa; Yokoyama, Yuusaku

    2011-10-21

    Palladium-catalyzed N-allylation of anthranilic acids 1a-j with allyl alcohol 2a in the presence of Pd(OAc)(2), sodium diphenylphosphinobenzene-3-sulfonate (TPPMS) in THF-H(2)O at room temperature gave only mono-N-allylated anthranilic acids 3a-j in good yields (70-98%). The reactions of 4-bromoanthranilic acid 1i with 2-methyl-3-buten-2-ol 2b showed complete chemoselectivity in N-allylation (neutral conditions) and C-vinylation (basic conditions). In our catalytic system, the keys to success are use of an unprotected anthranilic acid as a starting material and the presence of water in the reaction medium. The carboxyl group of anthranilic acid and water may play important roles for the smooth generation of the π-allyl palladium species by activation of the hydroxyl group of the allylic alcohol. PMID:21919524

  19. Auxiliary-assisted palladium-catalyzed arylation and alkylation of sp2 and sp3 carbon-hydrogen bonds.

    PubMed

    Shabashov, Dmitry; Daugulis, Olafs

    2010-03-24

    We have developed a method for auxiliary-directed, palladium-catalyzed beta-arylation and alkylation of sp(3) and sp(2) C-H bonds in carboxylic acid derivatives. The method employs a carboxylic acid 2-methylthioaniline- or 8-aminoquinoline amide substrate, aryl or alkyl iodide coupling partner, palladium acetate catalyst, and an inorganic base. By employing 2-methylthioaniline auxiliary, selective monoarylation of primary sp(3) C-H bonds can be achieved. If arylation of secondary sp(3) C-H bonds is desired, 8-aminoquinoline auxiliary may be used. For alkylation of sp(3) and sp(2) C-H bonds, 8-aminoquinoline auxiliary affords the best results. Some functional group tolerance is observed and amino- and hydroxy-acid derivatives can be functionalized. Preliminary mechanistic studies have been performed. A palladacycle intermediate has been isolated, characterized by X-ray crystallography, and its reactions have been studied.

  20. From bis(silylene) and bis(germylene) pincer-type nickel(II) complexes to isolable intermediates of the nickel-catalyzed Sonogashira cross-coupling reaction.

    PubMed

    Gallego, Daniel; Brück, Andreas; Irran, Elisabeth; Meier, Florian; Kaupp, Martin; Driess, Matthias; Hartwig, John F

    2013-10-16

    The first [ECE]Ni(II) pincer complexes with E = Si(II) and E = Ge(II) metallylene donor arms were synthesized via C-X (X = H, Br) oxidative addition, starting from the corresponding [EC(X)E] ligands. These novel complexes were fully characterized (NMR, MS, and XRD) and used as catalyst for Ni-catalyzed Sonogashira reactions. These catalysts allowed detailed information on the elementary steps of this catalytic reaction (transmetalation → oxidative addition → reductive elimination), resulting in the isolation and characterization of an unexpected intermediate in the transmetalation step. This complex, {[ECE]Ni acetylide → CuBr} contains both nickel and copper, with the copper bound to the alkyne π-system. Consistent with these unusual structural features, DFT calculations of the {[ECE]Ni acetylide → CuBr} intermediates revealed an unusual E-Cu-Ni three-center-two-electron bonding scheme. The results reveal a general reaction mechanism for the Ni-based Sonogashira coupling and broaden the application of metallylenes as strong σ-donor ligands for catalytic transformations. PMID:24053603

  1. Palladium-Catalyzed Synthesis of (Hetero)Aryl Alkyl Sulfones from (Hetero)Aryl Boronic Acids, Unactivated Alkyl Halides, and Potassium Metabisulfite.

    PubMed

    Shavnya, Andre; Hesp, Kevin D; Mascitti, Vincent; Smith, Aaron C

    2015-11-01

    A palladium-catalyzed one-step synthesis of (hetero)aryl alkyl sulfones from (hetero)arylboronic acids, potassium metabisulfite, and unactivated or activated alkylhalides is described. This transformation is of broad scope, occurs under mild conditions, and employs readily available reactants. A stoichiometric experiment has led to the isolation of a catalytically active dimeric palladium sulfinate complex, which was characterized by X-ray diffraction analysis.

  2. Pyrrolidine synthesis via palladium-catalyzed trimethylenemethane cycloaddition and related studies

    SciTech Connect

    Marrs, C.M.

    1992-01-01

    The palladium catalyzed trimethylenemethane cycloaddition has been extended to the synthesis of pyrrolidines and azepines. In contrast to previous attempts with N-alkyl and N-aryl imine, successful cycloadditions were recorded with several aromatic and aliphatic electron-deficient imines. Sulfonimines were found to be excellent acceptors, yielding pyrrolidine cycloadducts in excellent yields. Aromatic sulfonimines were observed to undergo cycloaddition very rapidly at or below room temperature. Some aliphatic nitrimine and N-phenyl, C-carbalkoxy imines were also found to be useful acceptors. Azepines were obtained from the cycloaddition of cisoid lockeed [alpha],[beta] unsaturated sulfonimines. In order to support the cycloaddition studies, a novel synthetic method was developed for the synthesis of sulfonimines. bis(Toluene-sulfonylimido)tellurium, Te(=N-Ts)[sub 2], generated from tellurium metal and anhydrous chloramine-t, was found to convert both aromatic and aliphatic aldehydes into the corresponding sulfonimines. Chiral ligands were examined in this cyclization and an enantiomeric excess of 35% was achieved with Hayashi's bidentate ferrocenyl ligand (BPFA). In support of this effort, the total synthesis of [+-] nicotine was accomplished in seven steps starting from pyridine 3-carboxaldehyde using these methodologies in order to verify the enantiomeric excess. Finally, the trimethylenemethane cycloaddition was examined with tropone irontricarbonyl complex. A novel [5+3] cycloaddition was observed to proceed in good yield, which upon decomplexation from the iron tricarbonyl moiety yielded the tricyclo[3.2.0] system. The scope and generality were briefly examined. Extended Huekel calculations were performed in order to help rationalize the unexpected regiochemistry.

  3. Palladium-Catalyzed Heteroarylation and Concomitant ortho-Alkylation of Aryl Iodides.

    PubMed

    Lei, Chuanhu; Jin, Xiaojia; Zhou, Jianrong Steve

    2015-11-01

    Three-component couplings were achieved from common aryl halides, alkyl halides, and heteroarenes under palladium and norbornene co-catalysis. The reaction forges hindered aryl-heteroaryl bonds and introduces ortho-alkyl groups to aryl rings. Various heterocycles such as oxazoles, thiazoles and thiophenes underwent efficient coupling. The heteroarenes were deprotonated in situ by bases without the assistance of palladium catalysts.

  4. Palladium-catalyzed combustion of methane: Simulated gas turbine combustion at atmospheric pressure

    SciTech Connect

    Griffin, T.; Weisenstein, W.; Scherer, V.; Fowles, M.

    1995-04-01

    Atmospheric pressure tests were performed in which a palladium catalyst ignites and stabilizes the homogeneous combustion of methane. Palladium exhibited a reversible deactivation at temperatures above 750 C, which acted to ``self-regulate`` its operating temperature. A properly treated palladium catalyst could be employed to preheat a methane/air mixture to temperatures required for ignition of gaseous combustion (ca. 800 C) without itself being exposed to the mixture adiabatic flame temperature. The operating temperature of the palladium was found to be relatively insensitive to the methane fuel concentration or catalyst inlet temperature over a wide range of conditions. Thus, palladium is well suited for application in the ignition and stabilization of methane combustion.

  5. Palladium-Catalyzed Oxidative Sulfenylation of Indoles and Related Electron-Rich Heteroarenes with Aryl Boronic Acids and Elemental Sulfur.

    PubMed

    Li, Jianxiao; Li, Chunsheng; Yang, Shaorong; An, Yanni; Wu, Wanqing; Jiang, Huanfeng

    2016-09-01

    An efficient and convenient palladium-catalyzed C-H bond oxidative sulfenylation of indoles and related electron-rich heteroarenes with aryl boronic acids and elemental sulfur has been described. This procedure provides a useful and direct approach for the assembly of a wide range of structurally diverse 3-sulfenylheteroarenes with moderate to excellent yields from simple and readily available starting materials. Moreover, this synthetic protocol is suitable for N-protected and unprotected indoles. Notably, the construction of two C-S bonds in one step was also achieved in this transformation. PMID:27500941

  6. Palladium-catalyzed synthesis of endocyclic allenes and their application in stereoselective [2 + 2]cycloaddition with ketenes.

    PubMed

    Ogasawara, Masamichi; Okada, Atsushi; Nakajima, Kiyohiko; Takahashi, Tamotsu

    2009-01-01

    Palladium-catalyzed reactions of various 2-bromo-3-exo-methylenecycloalkenes with a stabilized nucleophile were examined. When the carbocycles were nine-membered or larger, the corresponding endocyclic allenes were isolated in excellent yields. In a reaction of the eight-membered cyclic substrate, initial formation of a cycloocta-1,2-diene derivative was detected; however, it dimerized slowly. The seven-membered carbocycle was inert to the reaction. Using a chiral Pd-catalyst, an axially chiral endocyclic allene was obtained in 65% ee. The cyclic allenes were applied to [2 + 2]cycloaddition with ketenes, and the stereoselectivity was studied.

  7. 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

    2005-11-01

    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.

  8. Synthesis of 1,4:3,6-dianhydrohexitols diesters from the palladium-catalyzed hydroesterification reaction.

    PubMed

    Pruvost, Romain; Boulanger, Jérôme; Léger, Bastien; Ponchel, Anne; Monflier, Eric; Ibert, Mathias; Mortreux, André; Chenal, Thomas; Sauthier, Mathieu

    2014-11-01

    The hydroesterification of alpha olefins has been used to synthesize diesters from bio-based secondary diols: isosorbide, isomannide, and isoidide. The reaction was promoted by 0.2% palladium catalyst generated in situ from palladium acetate/triphenylphosphine/para-toluene sulfonic acid. Optimized reaction conditions allowed the selective synthesis of the diesters with high yields and the reaction conditions could be scaled up to the synthesis of hundred grams of diesters from isosorbide and 1-octene with solvent-free conditions.

  9. Asymmetric Copper-Catalyzed Carbozincation of Cyclopropenes en Route to the Formation of Diastereo- and Enantiomerically Enriched Polysubstituted Cyclopropanes.

    PubMed

    Müller, Daniel S; Marek, Ilan

    2015-12-16

    The enantioselective synthesis of cyclopropylzinc reagents has been achieved via a copper-catalyzed carbozincation of 3,3-disubstituted cyclopropenes with diorganozinc reagents. The obtained organozinc compounds can be easily functionalized with a broad range of electrophiles, including palladium-catalyzed cross-couplings, affording highly substituted cyclopropanes. The operationally simple procedure using very low quantities of a commercially available and inexpensive copper catalyst provides a new tool for the synthesis of highly enantioenriched cyclopropanes as single diastereoisomers. PMID:26624801

  10. Asymmetric Copper-Catalyzed Carbozincation of Cyclopropenes en Route to the Formation of Diastereo- and Enantiomerically Enriched Polysubstituted Cyclopropanes.

    PubMed

    Müller, Daniel S; Marek, Ilan

    2015-12-16

    The enantioselective synthesis of cyclopropylzinc reagents has been achieved via a copper-catalyzed carbozincation of 3,3-disubstituted cyclopropenes with diorganozinc reagents. The obtained organozinc compounds can be easily functionalized with a broad range of electrophiles, including palladium-catalyzed cross-couplings, affording highly substituted cyclopropanes. The operationally simple procedure using very low quantities of a commercially available and inexpensive copper catalyst provides a new tool for the synthesis of highly enantioenriched cyclopropanes as single diastereoisomers.

  11. Silicon-based cross-coupling reaction: an environmentally benign version.

    PubMed

    Nakao, Yoshiaki; Hiyama, Tamejiro

    2011-10-01

    Much attention has been paid to the cross-coupling reaction of organosilicon compounds due to their stability, non-toxicity, and natural abundance of silicon. In addition, the silicon-based cross-coupling has many advantages over other cross-coupling protocols. Successful examples of the silicon-based cross-coupling reaction are reviewed, focusing especially on the advances made in the last decade. Having had a number of highly effective palladium catalysts developed mainly for other cross-coupling reactions, the development of the silicon-based protocol owes heavily to the design of organosilicon reagents which effectively undergo transmetalation, a key elemental step of the silicon-based cross-coupling reaction. This tutorial review thus classifies various organosilicon reagents depending on substituents on silicon and surveys their cross-coupling reactions with various electrophiles.

  12. Total synthesis of protosappanin A and its derivatives via palladium catalyzed ortho C-H activation/C-C cyclization under microwave irradiation.

    PubMed

    Liu, Jiaqi; Zhou, Xuan; Wang, Chenglong; Fu, Wanyong; Chu, Wenyi; Sun, Zhizhong

    2016-04-14

    A total synthesis method for protosappanin A, which is a complex natural product with many biological activities, was developed with 6 linear steps. Dibenzo[b,d]oxepinones as the key intermediates of the synthetic route were prepared by a palladium-catalyzed ortho C-H activation/C-C cyclization under microwave irradiation. 25 derivatives of protosappanin A were obtained. PMID:26997503

  13. Direct conversion of allyl arenes to aryl ethylketones via a TBHP-mediated palladium-catalyzed tandem isomerization-Wacker oxidation of terminal alkenes.

    PubMed

    Zhao, JinWu; Liu, Li; Xiang, ShiJian; Liu, Qiang; Chen, HuoJi

    2015-05-28

    A TBHP-mediated palladium-catalyzed tandem isomerization-Wacker oxidation of terminal alkenes was developed. This methodology provides a new efficient and simple route for conversion of a range of allyl arenes directly into aryl ethylketones in good yields with high chemoselectivity.

  14. C8-Selective Acylation of Quinoline N-Oxides with α-Oxocarboxylic Acids via Palladium-Catalyzed Regioselective C-H Bond Activation.

    PubMed

    Chen, Xiaopei; Cui, Xiuling; Wu, Yangjie

    2016-08-01

    A facile and efficient protocol for palladium-catalyzed C8-selective acylation of quinoline N-oxides with α-oxocarboxylic acids has been developed. In this approach, N-oxide was utilized as a stepping stone for the remote C-H functionalization. The reactions proceeded efficiently under mild reaction conditions with excellent regioselectivity and broad functional group tolerance. PMID:27441527

  15. A Convenient Palladium-Catalyzed Carbonylative Synthesis of Benzofuran-2(3 H)-ones with Formic Acid as the CO Source.

    PubMed

    Qi, Xinxin; Li, Hao-Peng; Wu, Xiao-Feng

    2016-09-01

    A general and convenient palladium-catalyzed carbonylation procedure for the synthesis of benzofuran-2(3 H)-ones from phenols and aldehydes has been developed. With formic acid as the CO source, a variety of benzofuran-2(3 H)-ones were obtained in moderate to good yields. PMID:27539230

  16. Synthesis of steroid-ferrocene conjugates of steroidal 17-carboxamides via a palladium-catalyzed aminocarbonylation--copper-catalyzed azide-alkyne cycloaddition reaction sequence.

    PubMed

    Szánti-Pintér, Eszter; Balogh, János; Csók, Zsolt; Kollár, László; Gömöry, Agnes; Skoda-Földes, Rita

    2011-11-01

    Steroids with the 17-iodo-16-ene functionality were converted to ferrocene labeled steroidal 17-carboxamides via a two step reaction sequence. The first step involved the palladium-catalyzed aminocarbonylation of the alkenyl iodides with prop-2-yn-1-amine as the nucleophile in the presence of the Pd(OAc)(2)/PPh(3) catalyst system. In the second step, the product N-(prop-2-ynyl)-carboxamides underwent a facile azide-alkyne cycloaddition with ferrocenyl azides in the presence of CuSO(4)/sodium ascorbate to produce the steroid-ferrocene conjugates. The new compounds were obtained in good yield and were characterized by (1)H and (13)C NMR, IR, MS and elemental analysis. PMID:21787798

  17. One-pot palladium-catalyzed borrowing hydrogen synthesis of thioethers.

    PubMed

    Corma, Avelino; Navas, Javier; Ródenas, Tania; Sabater, María J

    2013-12-16

    Palladium on magnesium oxide is able to allow a one-pot reaction to synthesize thioethers from thiols and aldehydes formed in situ from the respective alcohol by means of a borrowing hydrogen method. The reaction is initiated by dehydrogenation of the alcohol to give a palladium hydride intermediate and an aldehyde. The latter reacts with a thiol involving most probably the intermediacy of a thionium ion RCH=S(+)R, which can be reduced in situ by the metal hydride to afford thioethers. PMID:24259460

  18. Palladium-catalyzed 2,5-diheteroarylation of 2,5-dibromothiophene derivatives

    PubMed Central

    Belkessam, Fatma; Mohand, Aidene; Soulé, Jean-François

    2014-01-01

    Summary Conditions allowing the one pot 2,5-diheteroarylation of 2,5-dibromothiophene derivatives in the presence of palladium catalysts are reported. Using KOAc as the base, DMA as the solvent and only 0.5–2 mol % palladium catalysts, the target 2,5-diheteroarylated thiophenes were obtained in moderate to good yields and with a wide variety of heteroarenes such as thiazoles, thiophenes, furans, pyrroles, pyrazoles or isoxazoles. Moreover, sequential heteroarylation reactions allow the access to 2,5-diheteroarylated thiophenes bearing two different heteroaryl units. PMID:25550758

  19. General reaction conditions for the palladium-catalyzed vinylation of aryl chlorides with potassium alkenyltrifluoroborates.

    PubMed

    Alacid, Emilio; Nájera, Carmen

    2009-11-01

    Activated and deactivated aryl and heteroaryl chlorides are efficiently cross-coupled with potassium vinyl- and alkenyltrifluoroborates using 4-hydroxyacetophenone oxime derived palladacycle as precatalyst in 1 to 3 mol % Pd loading, Binap as ligand, and Cs(2)CO(3) as base in DMF at 120 degrees C. The reactions can also be performed using Pd(OAc)(2) as Pd(0) source, although with lower efficiency. Bidentate ligands such as Binap and dppp can be used, the former being the best choice. Only in the case of deactivated aryl chlorides should the reaction temperature be increased to 160 degrees C to achieve good yields. The corresponding cross-coupled compounds, such as styrenes, stilbenes, and alkenylarenes, are obtained in good yields and with high regio- and diastereoselectivity.

  20. Palladium-catalyzed aerobic dehydrogenative aromatization of cyclohexanone imines to arylamines.

    PubMed

    Hajra, Alakananda; Wei, Ye; Yoshikai, Naohiko

    2012-11-01

    Dehydrogenative aromatization of cyclohexanone imines to arylamines has been achieved using a palladium catalyst under aerobic conditions. The reaction is applicable to a variety of imines that are either preformed or generated in situ from cyclohexanone derivatives and aryl or alkylamines.

  1. Palladium-catalyzed synthesis of dibenzophosphole oxides via intramolecular dehydrogenative cyclization.

    PubMed

    Kuninobu, Yoichiro; Yoshida, Takuya; Takai, Kazuhiko

    2011-09-16

    Dibenzophosphole oxides were obtained from secondary hydrophosphine oxides with a biphenyl group by dehydrogenation via phosphine-hydrogen and carbon-hydrogen bond cleavage in the presence of a catalytic amount of palladium(II) acetate, Pd(OAc)(2). By using this reaction, a ladder-type dibenzophosphole oxide could also be synthesized by double intramolecular dehydrogenative cyclization. PMID:21819045

  2. PALLADIUM CATALYZED COUPLING OF ARYL HALIDES WITH ARYLHALOSILANES IN AIR AND WATER. (R828129)

    EPA Science Inventory

    In the presence of a palladium catalyst, various aryl halides reacted with arylhalosilanes in aqueous media and under an air atmosphere to give the corresponding unsymmetrical aryl–aryl coupling products conveniently.

    Palladium(II)-Catalyzed Cyclization of Unsaturated Hydroperoxides for the Synthesis of 1,2-Dioxanes

    PubMed Central

    Harris, Jason R.; Waetzig, Shelli R.

    2009-01-01

    The cyclization of γ,δ-unsaturated tertiary hydroperoxides in the presence of a palladium(II) catalyst afforded 1,2-dioxanes resembling biologically active natural products. A variety of substrates were screened, and synthetic manipulations were accomplished to construct compounds with structural similarity to antimalarial targets. PMID:19555089

  3. 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

    2013-09-01

    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.

  4. Regioselective Allene Hydrosilylation Catalyzed by NHC Complexes of Nickel and Palladium

    PubMed Central

    Miller, Zachary D.; Li, Wei; Belderrain, Tomás R.; Montgomery, John

    2013-01-01

    Regioselective methods for allene hydrosilylation have been developed, with regioselectivity being governed primarily by choice of metal. Alkenylsilanes are produced via nickel catalysis with larger N-heterocyclic carbene ligands, and allylsilanes are produced via palladium catalysis with smaller N-heterocyclic carbene ligands. These complementary methods allow either regioisomeric product to be obtained with exceptional regiocontrol. PMID:24079389

  5. Synthesis of N-acylcarbazoles through palladium-catalyzed aryne annulation of 2-haloacetanilides.

    PubMed

    Lu, Chun; Markina, Nataliya A; Larock, Richard C

    2012-12-21

    N-Acylcarbazoles have been synthesized in moderate to good yields by the annulation of in situ generated arynes with 2-haloacetanilides in the presence of a palladium catalyst and CsF. Both C-C and C-N bonds are formed simultaneously, and a variety of functional groups are tolerated in this reaction. PMID:23214463

  6. Cross-coupling/cyclization reactions of two different allenic moieties.

    PubMed

    Alcaide, Benito; Almendros, Pedro; Martínez del Campo, Teresa

    2010-05-25

    The allene moiety represents an excellent building block for allene cross-coupling cyclization reactions, affording heterocyclic skeletons in a single step. This strategy is of particular interest when two different allene derivatives are involved in a series of metal-catalyzed cross-coupling heterocyclization processes. This Concept article is focused on the Pd-catalyzed union of two different allenic moieties, with cyclization of at least one of them by intramolecular cyclometalation. These new, versatile, and highly effective transformations are complex multistep processes leading to potential privileged structures that could find wide applications in related medicinal chemistry.

  7. The Enantioselective Construction of Tetracyclic Diterpene Skeletons with Friedel-Crafts Alkylation and Palladium-catalyzed Cycloalkenylation Reactions

    PubMed Central

    Burke, Sarah J.; Mehta, Sharan K.; Appenteng, Roselyn

    2015-01-01

    Due to the profound extent to which natural products inspire medicinal chemists in drug discovery, there is demand for innovative syntheses of these often complex materials. This article describes the synthesis of tricarbocyclic natural product architectures through an extension of the enantioselective Birch-Cope sequence with intramolecular Friedel-Crafts alkylation reactions. Additionally, palladium-catalyzed enol silane cycloalkenylation of the tricarbocyclic structures afforded the challenging bicyclo[3.2.1]octane C/D ring system found in the gibberellins and the ent-kauranes, two natural products with diverse medicinal value. In the case of the ent-kaurane derivative, an unprecedented alkene rearrangement converted four alkene isomers to one final product. PMID:25598198

  8. Palladium-catalyzed carbonylative coupling of (2-azaaryl)methyl anion equivalents with (hetero)aryl bromides.

    PubMed

    Jusseau, Xavier; Yin, Hongfei; Lindhardt, Anders T; Skrydstrup, Troels

    2014-11-24

    Conditions for the palladium-catalyzed coupling of (2-pyridyl)acetones with aryl bromides have been developed. Followed by an acid-promoted deacetylation step, the desired 1-(het)aryl-2-(2-pyridyl)ethanones were obtained in good to excellent yields with high functional group tolerance. Test reactions revealed that both the addition of MgCl2 and a specifically positioned heteroatom in the heteroaromatic ring were crucial for product formation indicating the importance of a chelated intermediate in the reaction mechanism. The reaction conditions proved suitable for a number of 5- and 6-membered heteroaromatic starting materials affording all products in good yields. The utility of the obtained 1-(het)aryl-2-(2-pyridyl)ethanones was demonstrated by the straightforward synthesis of several multiaromatic derivatives in only few additional steps.

  9. Synthesis of diverse β-quaternary ketones via palladium-catalyzed asymmetric conjugate addition of arylboronic acids to cyclic enones

    PubMed Central

    Holder, Jeffrey C.; Goodman, Emmett D.; Kikushima, Kotaro; Gatti, Michele; Marziale, Alexander N.; Stoltz, Brian M.

    2014-01-01

    The development and optimization of a palladium-catalyzed asymmetric conjugate addition of arylboronic acids to cyclic enone conjugate acceptors is described. These reactions employ air-stable and readily-available reagents in an operationally simple and robust transformation that yields β-quaternary ketones in high yields and enantioselectivities. Notably, the reaction itself is highly tolerant of atmospheric oxygen and moisture and therefore does not require the use of dry or deoxygenated solvents, specially purified reagents, or an inert atmosphere. The ring size and β-substituent of the enone are highly variable, and a wide variety of β-quaternary ketones can be synthesized. More recently, the use of NH4PF6 has further expanded the substrate scope to include heteroatom-containing arylboronic acids and β-acyl enone substrates. PMID:26461082

  10. The enantioselective construction of tetracyclic diterpene skeletons with Friedel-Crafts alkylation and palladium-catalyzed cycloalkenylation reactions.

    PubMed

    Burke, Sarah J; Malachowski, William P; Mehta, Sharan K; Appenteng, Roselyn

    2015-03-01

    Due to the profound extent to which natural products inspire medicinal chemists in drug discovery, there is demand for innovative syntheses of these often complex materials. This article describes the synthesis of tricarbocyclic natural product architectures through an extension of the enantioselective Birch-Cope sequence with intramolecular Friedel-Crafts alkylation reactions. Additionally, palladium-catalyzed enol silane cycloalkenylation of the tricarbocyclic structures afforded the challenging bicyclo[3.2.1]octane C/D ring system found in the gibberellins and the ent-kauranes, two natural products with diverse medicinal value. In the case of the ent-kaurane derivative, an unprecedented alkene rearrangement converted four alkene isomers to one final product. PMID:25598198

  11. Efficient synthesis of frutinone A and its derivatives through palladium-catalyzed C - H activation/carbonylation.

    PubMed

    Shin, Yongje; Yoo, Changho; Moon, Youngtaek; Lee, Yunho; Hong, Sungwoo

    2015-04-01

    Frutinone A, a biologically active ingredient of an antimicrobial herbal extract, demonstrates potent inhibitory activity towards the CYP1A2 enzyme. A three-step total synthesis of frutinone A with an overall yield of 44 % is presented. The construction of the chromone-annelated coumarin core was achieved through palladium-catalyzed CH carbonylation of 2-phenolchromones. The straightforward synthetic route allowed facile substitutions around the frutinone A core and thus rapid exploration of the structure-activity relationship (SAR) profile of the derivatives. The inhibitory activity of the synthesized frutinone A derivatives were determined for CYP1A2, and ten compounds exhibited one-to-two digit nanomolar inhibitory activity towards the CYP1A2 enzyme.

  12. Palladium-catalyzed one pot 2-arylquinazoline formation via hydrogen-transfer strategy.

    PubMed

    Wang, Huamin; Chen, Hui; Chen, Ya; Deng, Guo-Jun

    2014-10-21

    The palladium catalytic system was first applied to 2-arylquinazoline synthesis via hydrogen transfer methodology. Various (E)-2-nitrobenzaldehyde O-methyl oximes reacted easily with alcohols or benzyl amines to provide N-heterocyclic compounds in good to high yields. Similarly, the heterocyclic products could be prepared by the reaction of 1-(2-nitrophenyl)ethanone, urea and benzyl alcohols. In these reactions, the nitro group was reduced in situ by hydrogen generated from the alcohol dehydrogenation step. PMID:25156121

  13. A convenient and selective palladium-catalyzed aerobic oxidation of alcohols.

    PubMed

    Gowrisankar, Saravanan; Neumann, Helfried; Gördes, Dirk; Thurow, Kerstin; Jiao, Haijun; Beller, Matthias

    2013-11-18

    An efficient procedure for the oxidation of primary and secondary alcohols to aldehydes and ketones, respectively, with molecular oxygen under ambient conditions has been achieved. By applying catalytic amounts of Pd(OAc)2 in the presence of tertiary phosphine oxides (O=PR3) as ligands, a variety of substrates are selectively oxidized without formation of ester byproducts. Spectroscopic investigations and DFT calculations suggest stabilization of the active palladium(II) catalyst by phosphine oxide ligands.

  14. Palladium-Catalyzed ipso-Borylation of Aryl Sulfides with Diborons.

    PubMed

    Bhanuchandra, M; Baralle, Alexandre; Otsuka, Shinya; Nogi, Keisuke; Yorimitsu, Hideki; Osuka, Atsuhiro

    2016-06-17

    A catalytic Miyaura-type ipso-borylation of aryl sulfides with diboron reagents has been achieved, providing arylboronate esters of synthetic use. The key conditions to transform inherently reluctant C-S bonds into C-B bonds include a palladium-NHC (N-heterocyclic carbene) precatalyst, bis(pinacolato)diboron, and lithium hexamethyldisilazide. This protocol is applicable to a reasonable range of aryl alkyl sulfides. Twofold borylation was observed in the reaction of diphenyl sulfide. PMID:27267542

  15. Palladium-Catalyzed Aerobic Oxidative Dehydrogenation of Cyclohexenes to Substituted Arene Derivatives

    PubMed Central

    Iosub, Andrei V.; Stahl, Shannon S.

    2015-01-01

    A palladium(II) catalyst system has been identified for aerobic dehydrogenation of substituted cyclohexenes to the corresponding arene derivatives. Use of sodium anthraquinone-2-sulfonate (AMS) as a co-catalyst enhances the product yields. A wide range of functional groups are tolerated in the reactions, and the scope and limitations of the method are described. The catalytic dehydrogenation of cyclohexenes is showcased in an efficient route to a phthalimide-based TRPA1 activity modulator. PMID:25734414

  16. Palladium-Catalyzed ipso-Borylation of Aryl Sulfides with Diborons.

    PubMed

    Bhanuchandra, M; Baralle, Alexandre; Otsuka, Shinya; Nogi, Keisuke; Yorimitsu, Hideki; Osuka, Atsuhiro

    2016-06-17

    A catalytic Miyaura-type ipso-borylation of aryl sulfides with diboron reagents has been achieved, providing arylboronate esters of synthetic use. The key conditions to transform inherently reluctant C-S bonds into C-B bonds include a palladium-NHC (N-heterocyclic carbene) precatalyst, bis(pinacolato)diboron, and lithium hexamethyldisilazide. This protocol is applicable to a reasonable range of aryl alkyl sulfides. Twofold borylation was observed in the reaction of diphenyl sulfide.

  17. Efficient Synthesis of Diaryl Ketones by Nickel-Catalyzed Negishi Cross-Coupling of Amides by Carbon-Nitrogen Bond Cleavage at Room Temperature Accelerated by a Solvent Effect.

    PubMed

    Shi, Shicheng; Szostak, Michal

    2016-07-18

    The first Negishi cross-coupling of amides for the synthesis of versatile diaryl ketones by selective C-N bond activation under exceedingly mild conditions is reported. The cross-coupling was accomplished with bench-stable, inexpensive precatalyst [Ni(PPh3 )2 Cl2 ] that shows high functional-group tolerance and enables the synthesis of highly functionalized diaryl ketone motifs. The coupling occurred with excellent chemoselectivity favoring the ketone (cf. biaryl) products. Notably, this process represents the mildest conditions for amide N-C bond activation accomplished to date (room temperature, <10 min). Considering the versatile role of polyfunctional biaryl ketone linchpins in modern organic synthesis, availability, and excellent functional-group tolerance of organozinc reagents, this strategy provides a new platform for amide N-C bond/organozinc cross-coupling under mild conditions. PMID:27304392

  18. Decarboxylative Alkyl-Alkyl Cross-Coupling Reactions.

    PubMed

    Konev, Mikhail O; Jarvo, Elizabeth R

    2016-09-12

    Alkyl with alkyl: A significant development in alkyl-alkyl cross-coupling reactions, namely the nickel-catalyzed decarboxylative Negishi coupling of N-hydroxyphthalimide esters, was recently reported by Baran and co-workers. This method enables the synthesis of various highly functionalized compounds, including natural product derivatives.

  19. Introduction to Homogeneous Catalysis: Carbon-Carbon Bond Formation Catalyzed by a Defined Palladium Complex

    NASA Astrophysics Data System (ADS)

    Herrmann, Wolfgang A.; Böhm, Volker P. W.; Reisinger, Claus-Peter

    2000-01-01

    In this laboratory experiment students synthesize a phosphine ligand, P(o-tol)3, and with it the corresponding cyclometallated Pd(II) complex. This complex is an extremely active (pre)catalyst for C-C-bond-forming reactions (e.g. the Heck vinylation or the Grignard cross-coupling reaction). Students test the complex for activation in the catalysis of these two reactions using especially economical bromoaromatic compounds. The catalytic mechanisms of these reactions involve basic reaction types in organometallic chemistry such as ligand exchange, cyclometallation, oxidative addition, transmetallation, olefin insertion, reductive elimination and ß-hydride elimination. This experimental sequence combines synthetic organometallic and synthetic organic chemistry to introduce students to the field of catalysis as it appears in daily scientific research laboratory work.

  1. Accessing conjugated polymers with precisely controlled heterobisfunctional chain ends via post-polymerization modification of the OTf group and controlled Pd(0)/t-Bu3P-catalyzed Suzuki cross-coupling polymerization

    SciTech Connect

    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-Bu3P Suzuki cross-coupling polymerization with the post-polymerization modification of the triflate (OTf) group was disclosed.

  2. Accessing conjugated polymers with precisely controlled heterobisfunctional chain ends via post-polymerization modification of the OTf group and controlled Pd(0)/t-Bu3P-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-Bu3P Suzuki cross-coupling polymerization with the post-polymerization modification of the triflate (OTf) group was disclosed.

  3. Highly Efficient Cascade Reaction for Selective Formation of Spirocyclobutenes from Dienallenes via Palladium-Catalyzed Oxidative Double Carbocyclization–Carbonylation–Alkynylation

    PubMed Central

    2016-01-01

    A highly selective cascade reaction that allows the direct transformation of dienallenes to spirocyclobutenes (spiro[3.4]octenes) as single diastereoisomers has been developed. The reaction involves formation of overall four C–C bonds and proceeds via a palladium-catalyzed oxidative transformation with insertion of olefin, olefin, and carbon monoxide. Under slightly different reaction conditions, an additional CO insertion takes place to give spiro[4.4]nonenes with formation of overall five C–C bonds. PMID:27704805

  4. Palladium-Catalyzed Ortho-Selective C-H Oxidative Carbonylation of N-Substituted Anilines with CO and Primary Amines for the Synthesis of o-Aminobenzamides.

    PubMed

    Zhang, Xiaopeng; Dong, Shuxiang; Niu, Xueli; Li, Zhengwei; Fan, Xuesen; Zhang, Guisheng

    2016-09-16

    An efficient, one-pot strategy with high selectivity and high atom economy for the synthesis of o-aminobenzamides has been developed via palladium-catalyzed ortho-selective C-H oxidative carbonylation of N-substituted anilines with CO and primary amines. A wide range of N-substituted anilines and primary amines can be tolerated in this transformation to afford the corresponding o-aminobenzamides in moderate to excellent yields under mild conditions. PMID:27583815

  5. Synthesis of Strained γ-Lactams by Palladium(0)-Catalyzed C(sp(3) )-H Alkenylation and Application to Alkaloid Synthesis.

    PubMed

    Holstein, Philipp M; Dailler, David; Vantourout, Julien; Shaya, Janah; Millet, Anthony; Baudoin, Olivier

    2016-02-18

    A variety of strained α-alkylidene-γ-lactams were synthesized by palladium(0)-catalyzed intramolecular C(sp(3) )-H alkenylation from easily accessible acyclic and monocyclic bromoalkene precursors. These lactams are valuable intermediates for accessing various classes of mono- and bicylic alkaloids containing a pyrrolidine ring, as illustrated with the synthesis of an advanced model of the marine natural product plakoridine A and of the indolizidine alkaloid δ-coniceine.

  6. 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.

  7. Efficient synthesis of π-conjugated molecules incorporating fluorinated phenylene units through palladium-catalyzed iterative C(sp2)–H bond arylations

    PubMed Central

    Abdelmalek, Fatiha; Derridj, Fazia; Djebbar, Safia

    2015-01-01

    Summary We report herein a two or three step synthesis of fluorinated π-conjugated oligomers through iterative C–H bond arylations. Palladium-catalyzed desulfitative arylation of heteroarenes allowed in a first step the synthesis of fluoroaryl-heteroarene units in high yields. Then, the next steps involve direct arylation with aryl bromides catalyzed by PdCl(C3H5)(dppb) to afford triad or tetrad heteroaromatic compounds via regioselective activation of C(sp2)–H bonds. PMID:26664622

  8. Remarkable steric effect in palladium-catalyzed Grignard coupling: region- and stereoselective monoalkylation and -arylation of 1,1-dichloro-1-alkenes

    SciTech Connect

    Minato, A.; Suzuki, K.; Tamao, K.

    1987-02-18

    Functionalized carbon chain elongation has been a central concern in transition-metal complex catalyzed carbon-carbon bond-forming reactions. As part of their continued studies on the palladium-phosphine complex catalyzed selective monoalkylation of organic polyhalides, they report here the first success in the regio- and stereoselective monoalkylation and -arylation of 1,1-dichloro-1-alkenes by Grignard or organozinc reagents in the presence of (PdCl/sub 2/(dppb)), dppb = Ph/sub 2/P(CH/sub 2/)/sub 4/PPh/sub 2/, as a catalyst to produce 1-substituted (Z)-1-chloro-1-alkenes.

  9. Aqueous microwaves assisted cross-coupling reactions applied to unprotected nucleosides.

    NASA Astrophysics Data System (ADS)

    Len, Christophe; Hervé, Gwénaelle

    2015-02-01

    Nucleoside analogues have attracted much attention due to their potential biological activities. Amongst all synthetic nucleosides, C5-modified pyrimidines and C7- or C8-modified purines have mostly been prepared using palladium cross-coupling reactions and then studied as antitumoral and antiviral agents. Our objective is to focus this review on the Suzuki-Miyaura and on the Heck cross-couplings of nucleosides using microwave irradiations which are an alternative technology compatible with green chemistry and sustainable development.

  10. Suzuki-Miyaura cross-coupling reaction on copper-trans-A(2)B corroles with excellent functional group tolerance.

    PubMed

    König, Michael; Reith, Lorenz Michael; Monkowius, Uwe; Knör, Günther; Bretterbauer, Klaus; Schoefberger, Wolfgang

    2011-06-10

    The palladium-catalyzed Suzuki-Miyaura cross-coupling reaction has been investigated on meso-substituted trans-A(2)B-corrole using tailored Pd-catalyst systems.We present the first examples of Suzuki-Miyaura cross-coupling reactions on meso-substituted trans-A(2)B-corrole derivatives with neutral, sterically hindered, inactivated and heteroaromatic boronic acids and esters, alkenylboronic acids, as well as quickly deboronating aryl boronic acids and benzo-condensated five membered heterocyclic boronic acids. In addition, we established a high-yield procedure for the Suzuki-Miyaura cross-coupling reaction of corroles with neutral boronic acids.Due to the lability of the free-base corrole macrocycles, functionalization of the corrole periphery was performed with the corresponding Cu-metallated species. meso-Substituted trans-A(2)B-corrole can hence be regarded as highly versatile platform towards more sophisticated corrole systems.X-ray structure analysis of a functionalized meso-substituted trans-A(2)B copper corrole exhibited the typical features of such a Cu-complex: short N-Cu distances and a saddled corrole configuration.Moreover, we observed a sensitivity of the formal oxidation state of the coordinated copper ions towards Suzuki-Miyaura cross-coupling reaction conditions, where the central copper(III) ion approaches the characteristic features of a copper(II) species. This redox behaviour was examined by UV/vis absorption spectra, nuclear magnetic resonance (NMR) experiments and time-dependent density functional theoretical calculations. PMID:21760646

  11. Crystalline Isotactic Polar Polypropylene from the Palladium-Catalyzed Copolymerization of Propylene and Polar Monomers.

    PubMed

    Ota, Yusuke; Ito, Shingo; Kobayashi, Minoru; Kitade, Shinichi; Sakata, Kazuya; Tayano, Takao; Nozaki, Kyoko

    2016-06-20

    Moderately isospecific homopolymerization of propylene and the copolymerization of propylene and polar monomers have been achieved with palladium complexes bearing a phosphine-sulfonate ligand. Optimization of substituents on the phosphorus atom of the ligand revealed that the presence of bulky alkyl groups (e.g. menthyl) is crucial for the generation of high-molecular-weight polypropylenes (Mw ≈10(4) ), and the substituent at the ortho-position relative to the sulfonate group influences the molecular weight and isotactic regularity of the obtained polypropylenes. Statistical analysis suggested that the introduction of substituents at the ortho-position relative to the sulfonate group favors enantiomorphic site control over chain end control in the chain propagation step. The triad isotacticity could be increased to mm=0.55-0.59, with formation of crystalline polar polypropylenes, as supported by the presence of melting points and sharp peaks in the corresponding X-ray diffraction patterns. PMID:27161896

  12. Palladium-catalyzed direct C-H arylation of cyclic enaminones with aryl iodides.

    PubMed

    Yu, Yi-Yun; Bi, Lei; Georg, Gunda I

    2013-06-21

    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.

  13. On the Triple Role of Fluoride Ions in Palladium-Catalyzed Stille Reactions.

    PubMed

    Hervé, Marius; Lefèvre, Guillaume; Mitchell, Emily A; Maes, Bert U W; Jutand, Anny

    2015-12-01

    The mechanism of Stille reactions (cross-coupling of ArX with Ar'SnnBu3 ) performed in the presence of fluoride ions is established. A triple role for fluoride ions is identified from kinetic data on the rate of the reactions of trans-[ArPdBr(PPh3 )2 ] (Ar=Ph, p-(CN)C6 H4 ) with Ar'SnBu3 (Ar'=2-thiophenyl) in the presence of fluoride ions. Fluoride ions promote the rate-determining transmetallation by formation of trans-[ArPdF(PPh3 )2 ], which reacts with Ar'SnBu3 (Ar'=Ph, 2-thiophenyl) at room temperature, in contrast to trans-[ArPdBr(PPh3 )2 ], which is unreactive. However, the concentration ratio [F(-) ]/[Ar'SnBu3 ] must not be too high, because of the formation of unreactive anionic stannate [Ar'Sn(F)Bu3 ](-) . This rationalises the two kinetically antagonistic roles exerted by the fluoride ions that are observed experimentally, and is found to be in agreement with the kinetic law. In addition, fluoride ions promote reductive elimination from trans-[ArPdAr'(PPh3 )2 ] generated in the transmetallation step. PMID:26548772

  14. Palladium(II)-catalyzed copolymerization of styrenes with carbon monoxide: mechanism of chain propagation and chain transfer.

    PubMed

    Rix, Francis C; Rachita, Michael J; Wagner, Mark I; Brookhart, Maurice; Milani, Barbara; Barborak, James C

    2009-11-01

    A mechanistic interpretation of the [(1,10-phenanthroline)Pd(CH(3))(CH(3)CN)](+)[BArF](-) (1a) and [(2,2'-bipyridine)Pd(CH(3))(CH(3)CN)](+)[BArF](-) (1b) (BArF = 3,5-(CF(3))(2)-C(6)H(3)) catalyzed perfectly alternating copolymerization of styrenes with CO is reported. The copolymerization in CH(2)Cl(2) or chlorobenzene has been found to be first order in styrene and inverse first order in CO concentrations. The microscopic steps involved in the catalytic cycle have been studied via low temperature NMR techniques. Palladium alkyl chelate complex [(2,2'-bipyridine)Pd(CHArCH(2)C(O)CH(3)](+)[BArF](-) (5b sigma) and [(2,2'-bipyridine)Pd(eta(3)-CH(CH(2)C(O)CH(3))Ar)](+)[BArF](-) (5b pi), existing in equilibrium, were prepared. Treatment of 5b sigma,pi with (13)CO followed by 4-tert-butylstyrene at -78 degrees C allowed for (13)C NMR monitoring of the alternating chain growth of a series of palladium acyl carbonyl complexes. The acyl carbonyl species, representing the catalyst resting state, is in equilibrium with a palladium acyl styrene complex. The equilibrium constant, K(4), measured between [(phen)Pd(CO)(C(O)CH(3)](+)[BArF](-) (3a) and [(phen)Pd(C(O)CH(3))-(C(6)H(5)C=CH(2))](+)[BArF](-) (8a), was determined to be 2.84 +/- 2.8 x 10(-7) at -66 degrees C. The barrier to migratory insertion in 8a was determined (DeltaG(double dagger) (-66 degrees C) = 15.6 +/- 0.1 kcal mol(-1)). From the experimentally determined kinetic and thermodynamic data for the copolymerization of styrene with CO a mechanistic model has been constructed. The ability of this model to predict catalyst turnover frequency (TOF) was used as a test of its validity. A series of para-substituted styrenes, p-XC(6)H(4)CH=CH(2) (X = -OCH(3), -CH(3), -H, -Cl), were copolymerized with CO. A Hammett treatment of TOF for the series showed that electron-donating groups increase the rate of copolymerization (rho p = -0.8). The ratio of chain transfer to chain propagation was found to increase with styrene

  15. Palladium-Catalyzed Coupling of Functionalized Primary and Secondary Amines with Aryl and Heteroaryl Halides: Two Ligands Suffice in Most Cases†

    PubMed Central

    Maiti, Debabrata; Fors, Brett P.; Henderson, Jaclyn L.; Nakamura, Yoshinori; Buchwald, Stephen L.

    2012-01-01

    We report our studies on the use of two catalyst systems, based on the ligands BrettPhos (1) and RuPhos (2), which provide the widest scope for Pd-catalyzed C–N cross-coupling reactions to date. Often low catalyst loadings and short reaction times can be used with functionalized aryl and heteroaryl coupling partners. The reactions are highly robust and can be set up and performed without the use of a glovebox. These catalysts should find wide application in the synthesis of complex molecules including pharmaceuticals, natural products and functional materials. PMID:22384311

  16. Palladium-catalyzed allylic alkylation of simple ketones with allylic alcohols and its mechanistic study.

    PubMed

    Huo, Xiaohong; Yang, Guoqiang; Liu, Delong; Liu, Yangang; Gridnev, Ilya D; Zhang, Wanbin

    2014-06-23

    Allylic alcohols were directly used in Pd-catalyzed allylic alkylations of simple ketones under mild reaction conditions. The reaction proceeded smoothly at 20 °C by the concerted action of a Pd catalyst, a pyrrolidine co-catalyst, and a hydrogen-bonding solvent, and does not require any additional reagents. A computational study suggested that methanol plays a crucial role in the formation of the π-allylpalladium complex by lowering the activation barrier. PMID:24848670

  17. Palladium-Catalyzed Alkene Carboamination Reactions of Electron-Poor Nitrogen Nucleophiles

    PubMed Central

    Peterson, Luke J.

    2015-01-01

    Modified reaction conditions that facilitate Pd-catalyzed alkene carboamination reactions of electron-deficient nitrogen nucleophiles are reported. Pent-4-enylamine derivatives bearing N-tosyl or N-trifluoroacetyl groups are coupled with aryl triflates to afford substituted pyrrolidines in good yield. These reactions proceed via a mechanism involving anti-aminopalladation of the alkene, which differs from previously reported analogous reactions of N-aryl and N-boc pentenylamines. The application of these conditions to a formal synthesis of (±)-aphanorphine is also described. PMID:26622222

  18. Synthesis of fused imidazoles, pyrroles, and indoles with a defined stereocenter α to nitrogen utilizing Mitsunobu alkylation followed by palladium-catalyzed cyclization.

    PubMed

    Laha, Joydev K; Cuny, Gregory D

    2011-10-21

    Nitrogen-containing fused heterocycles comprise many compounds that demonstrate interesting biological activities. A new synthetic approach involving Mitsunobu alkylation of imidazoles, pyrroles, and indoles followed by palladium-catalyzed cyclization has been developed providing access to fused heterocycles with a defined stereochemistry α to nitrogen. While ethyl imidazole or indole carboxylates are good substrates for Mitsunobu alkylation with optically pure secondary benzylic alcohols, the corresponding pyrroles are poor substrates presumably due to the increased pK(a) of the NH. The presence of a synthetically versatile trichloroacetyl functional group on the pyrroles significantly reduces the pK(a) and thereby facilitates Mitsunobu alkylation. Subsequent cyclization of the alkylated products mediated by palladium in the presence or absence of a ligand gave fused heterocycles in good to excellent yields. PMID:21913645

  19. Synthesis of fused imidazoles, pyrroles, and indoles with a defined stereocenter α to nitrogen utilizing Mitsunobu alkylation followed by palladium-catalyzed cyclization.

    PubMed

    Laha, Joydev K; Cuny, Gregory D

    2011-10-21

    Nitrogen-containing fused heterocycles comprise many compounds that demonstrate interesting biological activities. A new synthetic approach involving Mitsunobu alkylation of imidazoles, pyrroles, and indoles followed by palladium-catalyzed cyclization has been developed providing access to fused heterocycles with a defined stereochemistry α to nitrogen. While ethyl imidazole or indole carboxylates are good substrates for Mitsunobu alkylation with optically pure secondary benzylic alcohols, the corresponding pyrroles are poor substrates presumably due to the increased pK(a) of the NH. The presence of a synthetically versatile trichloroacetyl functional group on the pyrroles significantly reduces the pK(a) and thereby facilitates Mitsunobu alkylation. Subsequent cyclization of the alkylated products mediated by palladium in the presence or absence of a ligand gave fused heterocycles in good to excellent yields.

  20. Scope and Limitations of Auxiliary-Assisted, Palladium-Catalyzed Arylation and Alkylation of sp2 and sp3 C-H Bonds

    PubMed Central

    Nadres, Enrico T.; Santos, Gerson Ivan Franco; Shabashov, Dmitry; Daugulis, Olafs

    2013-01-01

    The scope of palladium-catalyzed, auxiliary-assisted direct arylation and alkylation of sp2 and sp3 C-H bonds of amine and carboxylic acid derivatives has been investigated. The method employs a palladium acetate catalyst, substrate, aryl, alkyl, benzyl, or allyl halide, and inorganic base in t-amyl alcohol or water solvent at 100-140 °C. Aryl and alkyl iodides as well as benzyl and allyl bromides are competent reagents in this transformation. Picolinic acid auxiliary is used for amine γ-functionalization and 8-aminoquinoline auxiliary is used for carboxylic acid β-functionalization. Some optimization of base, additives, and solvent is required for achieving best results. PMID:24090404

  1. DFT studies on the palladium-catalyzed dearomatization reaction between naphthalene allyl chloride and allyltributylstannane.

    PubMed

    Cao, Wei; Tian, Dongxu; Han, Dongxue

    2015-10-01

    The Pd-catalyzed dearomatization of naphthalene allyl chloride with allyltributylstannane has been investigated using density functional theory (DFT) calculations at the B3LYP level. The calculations indicate that the (ŋ(1)-allyl)(ŋ(3)-allyl)Pd(PH3) complex is responsible for the formation of ortho-dearomatized product. Moreover it is easy to produce the ortho-dearomatized product when reductive elimination starts from (ŋ(3)-allylnaphthalene)(ŋ(1)-allyl)Pd complex 7, while it is easy to form the para-dearomatized product when reductive elimination starts from (ŋ(3)-allylnaphthalene)(ŋ(1)-allyl)Pd complex 9. The Stille coupling products can't be produced due to high reaction energy barrier. Graphical Abstract Two mechanisms of dearomatization are investigated by DFT, and (ŋ(1)-allyl)(ŋ(3)-allyl)Pd(PH3) complexes are the main intermediates for ortho-dearomatized product.

  2. 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

    2011-10-01

    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.

  3. Sulfonyl Azides as Precursors in Ligand-Free Palladium-Catalyzed Synthesis of Sulfonyl Carbamates and Sulfonyl Ureas and Synthesis of Sulfonamides.

    PubMed

    Chow, Shiao Y; Stevens, Marc Y; Odell, Luke R

    2016-04-01

    An efficient synthesis of sulfonyl carbamates and sulfonyl ureas from sulfonyl azides employing a palladium-catalyzed carbonylation protocol has been developed. Using a two-chamber system, sulfonyl azides, PdCl2, and CO gas, released ex situ from Mo(CO)6, were assembled to generate sulfonyl isocyanates in situ, and alcohols and aryl amines were exploited as nucleophiles to afford a broad range of sulfonyl carbamates and sulfonyl ureas. A protocol for the direct formation of substituted sulfonamides from sulfonyl azides and amines via nucleophilic substitution was also developed. PMID:26967791

  4. Palladium-Catalyzed Double C-H Functionalization of Arenes at the Positions ortho and meta to Their Directing Group: Concise Synthesis of Benzocyclobutenes.

    PubMed

    Nanjo, Takeshi; Tsukano, Chihiro; Takemoto, Yoshiji

    2016-01-01

    The synthesis of benzocyclobutenes from simple arenes bearing a directing group was investigated via the palladium-catalyzed cyclization of norbornene derivatives. This approach allowed for the facile construction of benzocyclobutenes along with the double functionalization of the C-H bonds at the positions ortho and meta to the directing group. This result shows that the key palladacyclopentene intermediate in the Catellani reaction can be prepared by the directed double ortho C-H activation of the substrate. The results of this study also revealed that the combination of an N-protected amino acid with benzoquinone (BQ) was effective for this transformation.

  5. Divergent reactivity in palladium-catalyzed annulation with diarylamines and α,β-unsaturated acids: direct access to substituted 2-quinolinones and indoles.

    PubMed

    Kancherla, Rajesh; Naveen, Togati; Maiti, Debabrata

    2015-06-01

    A palladium-catalyzed CH activation strategy has been successfully employed for exclusive synthesis of a variety of 3-substituted indoles. A [3+3] annulation for synthesizing substituted 2-quinolinones was recently developed by reaction of α,β-unsaturated carboxylic acids with diarylamines under acidic conditions. In the present work, an analogous [3+2] annulation is achieved from the same set of starting materials under basic conditions to generate 1,3-disubstituted indoles exclusively. Mechanistic studies revealed an ortho-palladation-π-coordination-β-migratory insertion-β-hydride elimination reaction sequence to be operative under the reaction conditions. PMID:25941155

  6. One-pot, two-step, microwave-assisted palladium-catalyzed conversion of aryl alcohols to aryl fluorides via aryl nonaflates.

    PubMed

    Wannberg, Johan; Wallinder, Charlotta; Ünlüsoy, Meltem; Sköld, Christian; Larhed, Mats

    2013-04-19

    A convenient procedure for converting aryl alcohols to aryl fluorides via aryl nonafluorobutylsulfonates (ArONf) is presented. Moderate to good one-pot, two-step yields were achieved by this nonaflation and microwave-assisted, palladium-catalyzed fluorination sequence. The reductive elimination step was investigated by DFT calculations to compare fluorination with chlorination, proving a larger thermodynamic driving force for the aryl fluoride product. Finally, a key aryl fluoride intermediate for the synthesis of a potent HCV NS3 protease inhibitor was smoothly prepared with the novel protocol.

  7. On the Mechanism of the Palladium-Catalyzed TBHP-Mediated Wacker-Type Oxidation of Alkenes using Quinoline-2-Oxazoline Ligands

    PubMed Central

    Michel, Brian W.; Steffens, Laura D.; Sigman, Matthew S.

    2011-01-01

    The mechanism of the tert-butylhydroperoxide-mediated, Pd(quinox)-catalyzed Wacker-type oxidation was investigated to evaluate the hypothesis that a selective catalyst-controlled oxidation could be achieved by rendering the palladium coordinatively saturated using a bidentate amine ligand. The unique role of the quinox ligand framework was probed via systematic ligand modifications. The modified ligands were evaluated through quantitative Hammett analysis, which supports a “push-pull” relationship between the electronically asymmetric quinoline and oxazoline ligand modules. PMID:21553838

  8. Palladium(II)-catalyzed intramolecular carboxypalladation-olefin insertion cascade: direct access to indeno[1,2-b]furan-2-ones.

    PubMed

    Vinoth, Perumal; Vivekanand, Thavaraj; Suryavanshi, Padmakar A; Menéndez, J Carlos; Sasai, Hiroaki; Sridharan, Vellaisamy

    2015-05-14

    A catalytic, atom-economical, domino 5-endo-dig cyclization-intramolecular olefin insertion sequence was developed under mild conditions. Aryl alkynoic acids bearing a tethered enone partner afforded the indeno[1,2-b]furan-2-ones, the core skeleton present in a number of biologically significant molecules including the natural product solanacol, under ligand-free, palladium-catalyzed reaction conditions in high yields. The competitive β-hydride elimination in the final step leading to the conjugated analogs was avoided by the addition of lithium bromide. A plausible mechanism for this domino sequence is proposed involving intramolecular carboxypalladation and olefin insertion steps.

  9. Copper(II)- and Palladium(II)-Catalyzed Enantioselective Claisen Rearrangement of Allyloxy- and Propargyloxy-Indoles to Quaternary Oxindoles and Spirocyclic Lactones

    PubMed Central

    Cao, Trung; Linton, Elizabeth C.; Deitch, Joshua; Berritt, Simon

    2012-01-01

    In this paper, a strategy to obtain highly enantioselective catalysts for the Claisen rearrangement of allyloxy- and propargyloxy-indoles is outlined. Ultimately, copper BOX and palladium BINAP or PHOX catalysts were discovered as superior in catalyzing Claisen rearrangements of allyloxy- or proparyloxy-substituted indoles to generate oxindoles bearing allyl- or allenyl-substituted quaternary centers. This method proved to be tolerant of a broad range of functional groups. Tandem reactions of the silyl-allene products provide rapid access to a variety of spirocyclic oxindoles in one operation. PMID:23167569

  10. Novel palladium complex-catalyzed reaction of magnesium amides with allylic electrophiles

    SciTech Connect

    Dzhemilev, U.M.; Ibragimov, A.G.; Minsker, D.L.; Muslukhov, R.R.

    1987-08-20

    In order to develop an efficient method for the synthesis of higher order unsaturated tertiary amines, and also to explore a new method for the formation of C-N bonds, they have investigated the transition metal complex-catalyzed reaction of magnesium amides with electrophiles; the electrophiles selected for study included allyl ethers and esters, as well as sulfones, sulfides and quaternized allylamines. The effects of the nature and structure of the catalyst components, as well as of the reaction conditions, on product yield were examined in the case of the reaction of diethyl (bromomagnesium)amine with diallyl ether, and revealed that the highest yield of diethylallyl-amine (I) was achieved using Pd(acac)/sub 2/ (3-5 mole %) and Ph/sub 3/P (1:2) as catalyst in THF solution at 50/sup 0/C for 5 h. Other transition metal (Ni, Fe, Zr, Ti, Cu) compounds were also examined as catalysts, but the yield of (I) did not exceed 15% with these compounds. Bimetallic catalysts based on Zr (Cp/sub 2/ZrCl, Py/sub 2/ZrCl/sub 6/, (RO)/sub 4/Zr) and Ni (Ni(acac)/sub 2/ and NiCl/sub 2/) were successful in forming (I) from diethyl (bromomagnesium)amine and diallyl ether in 60% yield.

  11. Controlling site selectivity in palladium-catalyzed C-H bond functionalization.

    PubMed

    Neufeldt, Sharon R; Sanford, Melanie S

    2012-06-19

    Effective methodology to functionalize C-H bonds requires overcoming the key challenge of differentiating among the multitude of C-H bonds that are present in complex organic molecules. This Account focuses on our work over the past decade toward the development of site-selective Pd-catalyzed C-H functionalization reactions using the following approaches: substrate-based control over selectivity through the use of directing groups (approach 1), substrate control through the use of electronically activated substrates (approach 2), or catalyst-based control (approach 3). In our extensive exploration of the first approach, a number of selectivity trends have emerged for both sp(2) and sp(3) C-H functionalization reactions that hold true for a variety of transformations involving diverse directing groups. Functionalizations tend to occur at the less-hindered sp(2) C-H bond ortho to a directing group, at primary sp(3) C-H bonds that are β to a directing group, and, when multiple directing groups are present, at C-H sites proximal to the most basic directing group. Using approach 2, which exploits electronic biases within a substrate, our group has achieved C-2-selective arylation of indoles and pyrroles using diaryliodonium oxidants. The selectivity of these transformations is altered when the C-2 site of the heterocycle is blocked, leading to C-C bond formation at the C-3 position. While approach 3 (catalyst-based control) is still in its early stages of exploration, we have obtained exciting results demonstrating that site selectivity can be tuned by modifying the structure of the supporting ligands on the Pd catalyst. For example, by modulating the structure of N-N bidentate ligands, we have achieved exquisite levels of selectivity for arylation at the α site of naphthalene. Similarly, we have demonstrated that both the rate and site selectivity of arene acetoxylation depend on the ratio of pyridine (ligand) to Pd. Lastly, by switching the ligand on Pd from an

  12. Controlling Site Selectivity in Palladium-Catalyzed C–H Bond Functionalization

    PubMed Central

    Neufeldt, Sharon R.; Sanford, Melanie S.

    2012-01-01

    Conspectus Effective methodology to functionalize C–H bonds requires overcoming the key challenge of differentiating among the multitude of C–H bonds that are present in complex organic molecules. This Account focuses on our work over the past decade toward the development of site-selective Pd-catalyzed C–H functionalization reactions using the following approaches: substrate-based control over selectivity through the use of directing groups (approach 1), substrate control through the use of electronically activated substrates (approach 2), or catalyst-based control (approach 3). In our extensive exploration of the first approach, a number of selectivity trends have emerged for both sp2 and sp3 C–H functionalization reactions that hold true for a variety of transformations involving diverse directing groups. Functionalizations tend to occur at the less-hindered sp2 C–H bond ortho to a directing group, at primary sp3 C–H bonds that are β to a directing group, and, when multiple directing groups are present, at C–H sites proximal to the most basic directing group. Using approach 2, which exploits electronic biases within a substrate, our group has achieved C-2-selective arylation of indoles and pyrroles using diaryliodonium oxidants. The selectivity of these transformations is altered when the C-2 site of the heterocycle is blocked, leading to C–C bond formation at the C-3 position. While approach 3 (catalyst-based control) is still in its early stages of exploration, we have obtained exciting results demonstrating that site selectivity can be tuned by modifying the structure of the supporting ligands on the Pd catalyst. For example, by modulating the structure of N~N bidentate ligands, we have achieved exquisite levels of selectivity for arylation at the α site of naphthalene. Similarly, we have demonstrated that both the rate and site selectivity of arene acetoxylation depend on the ratio of pyridine (ligand) to Pd. Lastly, by switching the ligand

  13. 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; Hong, Kunlun

    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

  14. 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

    SciTech Connect

    Zhang, Honghai; Xing, Chun-Hui; Hu, Qiao-Sheng; Hong, Kunlun

    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 paved the road to access well-defined conjugated polymers, including conjugated polymers with complex polymer architectures such as block copolymers and branch copolymers.

  15. Palladium-Catalyzed One-Pot Reaction of Hydrazones, Dihaloarenes, and Organoboron Reagents: Synthesis and Cytotoxic Activity of 1,1-Diarylethylene Derivatives.

    PubMed

    Roche, Maxime; Salim, Salim Mmadi; Bignon, Jérôme; Levaique, Hélène; Brion, Jean-Daniel; Alami, Mouad; Hamze, Abdallah

    2015-07-01

    A new three-component assembly reaction between N-tosylhydrazones, dihalogenated arenes, and boronic acids or boronate esters was developed, producing highly substituted 1,1-diarylethylenes in good yields. The two C-C bonds formed through this coupling have been catalyzed by a single Pd-catalyst in a one-pot fashion. It is noted that the one-pot pinacol boronate cross-coupling reaction generally provides products in high yields, offers an expansive substrate scope, and can address a broad range of aryl, styrene, vinyl, and heterocyclic olefinic targets. The scope of this one-pot coupling has been also extended to the synthesis of the 1,1-diarylethylene skeleton of the natural product ratanhine. The new compounds were evaluated for their cytotoxic activity, and this allowed the identification of compound 4ab that exhibits excellent antiproliferative activity in the nanomolar concentration range against HCT116 cancer cell lines. PMID:26036279

  16. Palladium-Catalyzed One-Pot Reaction of Hydrazones, Dihaloarenes, and Organoboron Reagents: Synthesis and Cytotoxic Activity of 1,1-Diarylethylene Derivatives.

    PubMed

    Roche, Maxime; Salim, Salim Mmadi; Bignon, Jérôme; Levaique, Hélène; Brion, Jean-Daniel; Alami, Mouad; Hamze, Abdallah

    2015-07-01

    A new three-component assembly reaction between N-tosylhydrazones, dihalogenated arenes, and boronic acids or boronate esters was developed, producing highly substituted 1,1-diarylethylenes in good yields. The two C-C bonds formed through this coupling have been catalyzed by a single Pd-catalyst in a one-pot fashion. It is noted that the one-pot pinacol boronate cross-coupling reaction generally provides products in high yields, offers an expansive substrate scope, and can address a broad range of aryl, styrene, vinyl, and heterocyclic olefinic targets. The scope of this one-pot coupling has been also extended to the synthesis of the 1,1-diarylethylene skeleton of the natural product ratanhine. The new compounds were evaluated for their cytotoxic activity, and this allowed the identification of compound 4ab that exhibits excellent antiproliferative activity in the nanomolar concentration range against HCT116 cancer cell lines.

  17. Synthesis of E-Alkyl Alkenes from Terminal Alkynes via Ni-Catalyzed Cross-Coupling of Alkyl Halides with B-Alkenyl-9-borabicyclo[3.3.1]nonanes.

    PubMed

    Di Franco, Thomas; Epenoy, Alexandre; Hu, Xile

    2015-10-01

    The first Ni-catalyzed Suzuki-Miyaura coupling of alkyl halides with alkenyl-(9-BBN) reagents is reported. Both primary and secondary alkyl halides including alkyl chlorides can be coupled. The coupling method can be combined with hydroboration of terminal alkynes, allowing the expedited synthesis of functionalized alkyl alkenes from readily available alkynes with complete (E)-selectivity in one pot. The method was applied to the total synthesis of (±)-Recifeiolide, a natural macrolide.

  18. Aqueous microwave-assisted cross-coupling reactions applied to unprotected nucleosides.

    PubMed

    Hervé, Gwénaëlle; Len, Christophe

    2015-01-01

    Metal catalyzed cross-coupling reactions have been the preferred tools to access to modified nucleosides (on the C5-position of pyrimidines and on the C7- or C8-positions of purines). Our objective is to focus this mini-review on the Suzuki-Miyaura and on the Heck cross-couplings of nucleosides using microwave irradiations which is an alternative technology compatible with green chemistry and sustainable development.

  19. Activation of "inert" alkenyl/aryl C-O bond and its application in cross-coupling reactions.

    PubMed

    Li, Bi-Jie; Yu, Da-Gang; Sun, Chang-Liang; Shi, Zhang-Jie

    2011-02-01

    Enol and phenol functionalities are very common in organic molecules. Utilization of these materials is very appealing in organic synthesis because they are important alternatives to organohalides in cross-coupling reactions. In this review, we summarize the transition-metal-catalyzed cross-coupling of enol- and phenol-based electrophiles, including phosphates, sulfonates, ethers, carboxylates, and phenolates.

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

    SciTech Connect

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

    2015-01-01

    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.

  1. A convenient method for palladium-catalyzed reductive deuteration of organic substrates using deuterated hypophosphite in D2O.

    PubMed

    Oba, Makoto

    2015-05-15

    A convenient method for the deuteration of organic substrates using deuterated hypophosphite as the deuterium source was investigated. Transfer deuteration of organic substrates, such as aromatic halides, alkenes, alkynes, epoxides, and O-benzyl derivatives, in the presence of palladium on carbon in deuterium oxide proceeded efficiently to give the corresponding deuterated products in excellent yields with high deuterium contents. PMID:25732435

  2. Preparation of vinylogous 2-sulfonylindolines by the palladium-catalyzed heteroannulation of o-iodoanilines with dienyl sulfones and their further transformation to indoles and carbazoles.

    PubMed

    Back, T G; Bethell, R J; Parvez, M; Taylor, J A

    2001-12-14

    The palladium-catalyzed heteroannulation of o-iodoanilines with dienyl sulfones provides a convenient route to vinylogous 2-sulfonylindolines 3. The reaction proceeds in DMF/water in the presence of potassium carbonate and catalytic palladium(II) acetate and is compatible with both electron-donating and -withdrawing substituents in the para position of the aniline, and with an alkyl substituent at C-2 of the dienyl sulfone. The indolines underwent oxidation with DDQ to afford the corresponding indoles 4. The latter were then employed as dienes in Diels-Alder reactions with dimethyl acetylenedicarboxylate (DMAD), methyl propiolate, or methyl acrylate. In the case of the latter two dienophiles, the cycloadditions were highly regioselective, affording the corresponding 1,3-products (with respect to the relative positions of the sulfone and ester groups), exclusively. The cycloadducts from acetylenic dienophiles were converted to the corresponding carbazoles by elimination of the sulfone moiety with DBU, and that from methyl acrylate was subjected to reductive desulfonylation and oxidation to the corresponding carbazole with DDQ. The method thus provides access to carbazoles with various substituents at the 3-, 4-, and 6-positions. PMID:11735543

  3. Development of Stereocontrolled Palladium(II)-Catalyzed Domino Heck/Suzuki β,α-Diarylation Reactions with Chelating Vinyl Ethers and Arylboronic Acids

    PubMed Central

    Trejos, Alejandro; Odell, Luke R; Larhed, Mats

    2012-01-01

    A stereoselective and 1,4-benzoquinone-mediated palladium(II)-catalyzed Heck/Suzuki domino reaction involving metal coordinating cyclic methylamino vinyl ethers and a number of electronically diverse arylboronic acids has been developed and studied. Diastereomeric ratios up to 39:1 and 78 % isolated yields were obtained. The stereoselectivity of the reaction was found to be highly dependent on the nature of the arylboronic acid and the amount of water present in the reaction mixture. Thus, a domino β,α-diarylation–reduction of chelating vinyl ethers can now be accomplished and stereochemically controlled, given that optimized conditions and an appropriate chiral auxiliary are used. To the best of our knowledge, this represents the first example of a stereoselective, oxidative Heck/Suzuki domino reaction in the literature. PMID:24551492

  4. Double C-H functionalization in sequential order: direct synthesis of polycyclic compounds by a palladium-catalyzed C-H alkenylation-arylation cascade.

    PubMed

    Ohno, Hiroaki; Iuchi, Mutsumi; Kojima, Naoto; Yoshimitsu, Takehiko; Fujii, Nobutaka; Tanaka, Tetsuaki

    2012-04-23

    Palladium-catalyzed cascade C-H alkenylation and arylation provides convenient access to polycyclic aromatic compounds. Treatment of 3-bromoaniline derivatives bearing a bromocinnamyl group on the nitrogen atom with a catalytic amount of [Pd(OAc)(2)] and PCy(3)·HBF(4) in the presence of Cs(2)CO(3) in dioxane affords naphthalene-fused indole derivatives in good yields. This double cyclization reaction is also applicable to heterocyclic substrates, giving fused indoles containing a heteroaromatic ring such as dibenzofuran, dibenzothiophene, carbazole, indole, or benzofuran through heterocyclic C-H arylation. When using a 2,6-unsubstituted aniline derivative, the first C-H arylation preferentially proceeds at the more hindered position of the aniline ring.

  5. Catalysts for cross-coupling reactions with non-activated alkyl halides.

    PubMed

    Frisch, Anja C; Beller, Matthias

    2005-01-21

    Despite the problems inherent to metal-catalyzed cross-coupling reactions with alkyl halides, these reactions have become increasingly important during the last few years. Detailed mechanistic investigations have led to a variety of novel procedures for the selective cross-coupling of non-activated alkyl halides bearing beta hydrogen atoms with a variety of organometallic nucleophiles under mild reaction conditions. This Minireview highlights selected examples of metal-catalyzed coupling methods and is intended to encourage chemists to exploit the potential of these approaches in organic synthesis.

  6. Iron-catalysed cross-coupling of organolithium compounds with organic halides

    PubMed Central

    Jia, Zhenhua; Liu, Qiang; Peng, Xiao-Shui; Wong, Henry N. C.

    2016-01-01

    In past decades, catalytic cross-coupling reactions between organic halides and organometallic reagents to construct carbon–carbon bond have achieved a tremendous progress. However, organolithium reagents have rarely been used in cross-coupling reactions, due mainly to their high reactivity. Another limitation of this transformation using organolithium reagents is how to control reactivity with excellent selectivity. Although palladium catalysis has been applied in this field recently, the development of an approach to replace catalytic systems of noble metals with nonprecious metals is currently in high demand. Herein, we report an efficient synthetic protocol involving iron-catalysed cross-coupling reactions employing organolithium compounds as key coupling partners to unite aryl, alkyl and benzyl fragments and also disclose an efficient iron-catalysed release-capture ethylene coupling with isopropyllithium. PMID:26847602

  7. Iterative protecting group-free cross-coupling leading to chiral multiply arylated structures

    PubMed Central

    Crudden, Cathleen M.; Ziebenhaus, Christopher; Rygus, Jason P. G.; Ghozati, Kazem; Unsworth, Phillip J.; Nambo, Masakazu; Voth, Samantha; Hutchinson, Marieke; Laberge, Veronique S.; Maekawa, Yuuki; Imao, Daisuke

    2016-01-01

    The Suzuki–Miyaura cross-coupling is one of the most often utilized reactions in the synthesis of pharmaceutical compounds and conjugated materials. In its most common form, the reaction joins two sp2-functionalized carbon atoms to make a biaryl or diene/polyene unit. These substructures are widely found in natural products and small molecules and thus the Suzuki–Miyaura cross-coupling has been proposed as the key reaction for the automated assembly of such molecules, using protecting group chemistry to affect iterative coupling. We present herein, a significant advance in this approach, in which multiply functionalized cross-coupling partners can be employed in iterative coupling without the use of protecting groups. To accomplish this, the orthogonal reactivity of different boron substituents towards the boron-to-palladium transmetalation reaction is exploited. The approach is illustrated in the preparation of chiral enantioenriched compounds, which are known to be privileged structures in active pharmaceutical compounds. PMID:27040494

  8. Palladium-catalyzed carbon-monoxide-free aminocarbonylation of aryl halides using N-substituted formamides as an amide source.

    PubMed

    Sawant, Dinesh N; Wagh, Yogesh S; Bhatte, Kushal D; Bhanage, Bhalchandra M

    2011-07-01

    A carbon-monoxide-free aminocarbonylation of various N-substituted formamides with aryl iodides and aryl bromides using palladium acetate and Xantphos is described. The developed methodology is applicable for a wide range of formamides and aryl halides containing different functional groups furnishing good to excellent yield of the corresponding products. N-substituted formamides are used as an amide source wherein a Vilsmeier-type intermediate plays a major role, thus eliminating the need of toxic carbon monoxide gas. PMID:21618964

  9. Palladium-Catalyzed Site-Selective C-H Functionalization of Weakly Coordinating Sulfonamides: Synthesis of Biaryl Sulfonamides.

    PubMed

    Vanjari, Rajeshwer; Guntreddi, Tirumaleswararao; Singh, Krishna Nand

    2016-03-01

    A novel and site selective C-H functionalization of unsubstituted sulfonamides has been developed for the synthesis of ortho aryl sulfonamides. The reaction involves highly regioselective ortho mono arylation of weakly coordinating SO2 NH2 directing group by means of aryl iodides. Palladium acetate in the presence of silver(I) oxide is found to be the most effective catalytic system. PMID:26763530

  10. Intramolecular transfer of {open_quotes}CO{close_quotes} from ({eta}{sup 6}-arene)Cr(CO){sub 3} complexes in stille-type palladium-catalyzed cross coupling reactions

    SciTech Connect

    Caldirola, P.; Chowdhury, R.; Johansson, A.M.; Hacksell, U.

    1995-12-31

    The reaction between [{eta}{sup 6}-(trialkylstannyl)benzene]Cr(CO){sub 3} complexes and different electrophiles such as iodobenzene and aryltriflate and the coupling between (tributylphenyl)stannane and the Cr(CO){sub 3} complex of chlorobenzene have been studied. Products from two different types of reactions were observed: (1) benzophenone along with the alkylarylketone, resulting from a carbonylative coupling, and (2) biphenyl, arising from a direct coupling.

  11. Palladium catalyzed coupling reactions: mechanism of reductive elimination. Progress report, October 1, 1979-September 30, 1980. [Ethane elimination

    SciTech Connect

    Stille, J.K.

    1980-09-01

    The 1,1-reductive elimination of ethane from three cis-bis(phosphine)-dimethylpalladium complexes, L/sub 2/Pd(CH/sub 3/)/sub 2/ (L = PPh/sub 3/, PPh/sub 2/,CH/sub 3/ and L/sub 2/ = Ph/sub 2/PCH/sub 2/CH/sub 2/PPh/sub 2/), and three trans analogs (L = PPh/sub 3/, PPh/sub 2/CH/sub 3/ and L/sub 2/ = 2,11-bis(diphenylphosphinomethyl)benzo(c)phenanthrene (TRANSPHOS)) was carried out. The three cis complexes underwent reductive elimination in the presence of coordinating solvents (DMSO, DMF, and THF). The trans complexes which could isomerize to cis (L = PPh/sub 3/, PPh/sub 2/CH/sub 3/) did so in polar solvents and then underwent reductive elimination. TRANSPHOS dimethylpalladium would not undergo reductive elimination of ethane. The eliminations from the cis isomers were intramolecular and displayed first order kinetics. Although TRANSPHOS dimethylpalladium(II) would not undergo a 1,1-reductive elimination of ethane, the addition of CD/sub 3/I to a DMSO solution of this complex at 25/sup 0/C rapidly produced CD/sub 3/-CH/sub 3/, implicating a transient palladium(IV) intermediate. E- and Z-bromostyrylbis(diphenylmethylphosphine)palladium(0) react with methyl lithium in THF at ambient temperature to give the E- and Z- propenylbenzenes, respectively. At -78/sup 0/C, the intermediate E- and Z-styrylmethylbis(diphenylmethylphosphine)palladium(II) complexes (9a,b) can be isolated. On raising the temperature of solutions of 9a,b in THF, E- and Z-propenylbenzenes are produced. The reductive elimination reaction is intramolecular and first order in dialkylpalladium(II) complex.

  12. 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.

  13. Photoredox-Catalyzed Stereoselective Conversion of Alkynes into Tetrasubstituted Trifluoromethylated Alkenes.

    PubMed

    Tomita, Ren; Koike, Takashi; Akita, Munetaka

    2015-10-26

    A regio- and stereoselective synthesis of trifluoromethylated alkenes bearing four different substituents has been developed. Stereocontrolled sulfonyloxytrifluoromethylation of unsymmetric internal alkynes with an electrophilic CF3 reagent, namely the triflate salt of the Yagupol'skii-Umemoto reagent, in the presence of an Ir photoredox catalyst under visible-light irradiation afforded trifluoromethylalkenyl triflates with well-predictable stereochemistry resulting from anti addition of the trifluoromethyl and triflate groups. Subsequent palladium-catalyzed cross-couplings led to tetrasubstituted trifluoromethylated alkenes in a highly stereoselective manner. The present method is the first example of a facile one-pot synthesis of tetrasubstituted trifluoromethylated alkenes from simple alkynes.

  14. A Novel synthesis of 2-functionalized benzofurans by palladium-catalyzed cycloisomerization of 2-(1-hydroxyprop-2-ynyl)phenols followed by acid-catalyzed allylic isomerization or allylic nucleophilic substitution.

    PubMed

    Gabriele, Bartolo; Mancuso, Raffaella; Salerno, Giuseppe

    2008-09-19

    A novel two-step synthesis of 2-hydroxymethylbenzofurans 3 and 2-alkoxymethylbenzofurans 4-6, based on palladium-catalyzed cycloisomerization of 2-(1-hydroxyprop-2-ynyl)phenols 1 under basic conditions to give 2-methylene-2,3-dihydrobenzofuran-3-ols 2, followed by acid-catalyzed isomerization or allylic nucleophilic substitution with alcohols as nucleophiles, is reported. Cycloisomerization reactions leading to 2 (80-98% yields) were carried out at 40 degrees C in MeOH as the solvent, in the presence of a base and catalytic amounts of PdX2 + 2KX (X = Cl, I). Isomerization reactions of 2 readily occurred at 25-60 degrees C in DME as the solvent, with H2SO4 as the proton source, to give 2-hydroxymethylbenzofurans 3 in 65-90% yields. In a similar manner, allylic nucleophilic substitution reactions of 2 with ROH as nucleophiles [carried out at 25-40 degrees C in ROH (R = Me) or ROH-DME mixtures (R = Bu, Bn) in the presence of H2SO4] afforded 2-alkoxymethylbenzofurans 4, 5, and 6 (R = Me, Bu, and Bn, respectively), in 65-98% yields.

  15. Palladium-Catalyzed Long-Range Deconjugative Isomerization of Highly Substituted α,β-Unsaturated Carbonyl Compounds.

    PubMed

    Lin, Luqing; Romano, Ciro; Mazet, Clément

    2016-08-17

    The long-range deconjugative isomerization of a broad range of α,β-unsaturated amides, esters, and ketones by an in situ generated palladium hydride catalyst is described. This redox-economical process is triggered by a hydrometalation event and is thermodynamically driven by the refunctionalization of a primary or a secondary alcohol into an aldehyde or a ketone. Di-, tri-, and tetrasubstituted carbon-carbon double bonds react with similar efficiency; the system is tolerant toward a variety of functional groups, and olefin migration can be sustained over 30 carbon atoms. The refunctionalized products are usually isolated in good to excellent yield. Mechanistic investigations are in support of a chain-walking process consisting of repeated migratory insertions and β-H eliminations. The bidirectionality of the isomerization reaction was established by isotopic labeling experiments using a substrate with a double bond isolated from both terminal functions. The palladium hydride was also found to be directly involved in the product-forming tautomerization step. The ambiphilic character of the in situ generated [Pd-H] was demonstrated using isomeric trisubstituted α,β-unsaturated esters. Finally, the high levels of enantioselectivity obtained in the isomerization of a small set of α-substituted α,β-unsaturated ketones augur well for the successful development of an enantioselective version of this unconventional isomerization. PMID:27434728

  16. Suzuki-Miyaura cross-coupling of potassium dioxolanylethyltrifluoroborate and aryl/heteroaryl chlorides.

    PubMed

    Fleury-Brégeot, Nicolas; Oehlrich, Daniel; Rombouts, Frederik; Molander, Gary A

    2013-04-01

    A robust and efficient protocol for the introduction of the dioxolanylethyl moiety onto various aryl and heteroaryl halides has been developed, providing cross-coupling yields up to 93%. Copper-catalyzed borylation of 2-(2-bromoethyl)-1,3-dioxolane with bis(pinacolato)diboron followed by treatment with potassium bifluoride provides the key organotrifluoroborate reagent.

  17. Suzuki-Miyaura Cross-Coupling of Potassium Dioxolanylethyltrifluoroborate and Aryl/Heteroaryl Chlorides

    PubMed Central

    Fleury-Brégeot, Nicolas; Oehlrich, Daniel; Rombouts, Frederik

    2013-01-01

    A robust and efficient protocol for the introduction of the dioxolanylethyl moiety onto various aryl and heteroaryl halides has been developed, providing cross-coupling yields up to 93%. Copper-catalyzed borylation of 2-(2-bromoethyl)-1,3-dioxolane with bis(pinacolato)diboron followed by treatment with potassium bifluoride provides the key organotrifluoroborate reagent. PMID:23489071

  18. Suzuki-Miyaura cross-coupling of potassium dioxolanylethyltrifluoroborate and aryl/heteroaryl chlorides.

    PubMed

    Fleury-Brégeot, Nicolas; Oehlrich, Daniel; Rombouts, Frederik; Molander, Gary A

    2013-04-01

    A robust and efficient protocol for the introduction of the dioxolanylethyl moiety onto various aryl and heteroaryl halides has been developed, providing cross-coupling yields up to 93%. Copper-catalyzed borylation of 2-(2-bromoethyl)-1,3-dioxolane with bis(pinacolato)diboron followed by treatment with potassium bifluoride provides the key organotrifluoroborate reagent. PMID:23489071

  19. 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 Ph

  20. Transition-metal-catalyzed C-S bond coupling reaction.

    PubMed

    Lee, Chin-Fa; Liu, Yi-Chen; Badsara, Satpal Singh

    2014-03-01

    Sulfur-containing molecules such as thioethers are commonly found in chemical biology, organic synthesis, and materials chemistry. While many reliable methods have been developed for preparing these compounds, harsh reaction conditions are usually required in the traditional methods. The transition metals have been applied in this field, and the palladium-catalyzed coupling of thiols with aryl halides and pseudo halides is one of the most important methods in the synthesis of thioethers. Other metals have also been used for the same purpose. Here, we summarize recent efforts in metal-catalyzed C-S bond cross-coupling reactions, focusing especially on the coupling of thiols with aryl- and vinyl halides based on different metals.

  1. Palladium-Catalyzed Zinc-Amide-Mediated C-H Arylation of Fluoroarenes and Heteroarenes with Aryl Sulfides.

    PubMed

    Otsuka, Shinya; Yorimitsu, Hideki; Osuka, Atsuhiro

    2015-10-12

    C-H arylation of polyfluoroarenes and heteroarenes with aryl sulfides proceeds smoothly with the aid of a palladium-N-heterocyclic carbene catalyst. A bulky zinc amide, TMPZnCl⋅LiCl, plays a key role as an effective base to generate the corresponding arylzinc species in situ. This arylation protocol is practically much easier to perform than our previous method, which necessitates preparation of the arylzinc reagents in advance from the corresponding aryl halides. Aryl sulfides that are prepared through sulfur-specific reactions, such as SN Ar sulfanylation and extended Pummerer reactions, undergo this direct arylation, offering interesting transformations that are otherwise difficult to achieve with conventional halogen-based organic synthesis. PMID:26235212

  2. Palladium-Catalyzed Zinc-Amide-Mediated C-H Arylation of Fluoroarenes and Heteroarenes with Aryl Sulfides.

    PubMed

    Otsuka, Shinya; Yorimitsu, Hideki; Osuka, Atsuhiro

    2015-10-12

    C-H arylation of polyfluoroarenes and heteroarenes with aryl sulfides proceeds smoothly with the aid of a palladium-N-heterocyclic carbene catalyst. A bulky zinc amide, TMPZnCl⋅LiCl, plays a key role as an effective base to generate the corresponding arylzinc species in situ. This arylation protocol is practically much easier to perform than our previous method, which necessitates preparation of the arylzinc reagents in advance from the corresponding aryl halides. Aryl sulfides that are prepared through sulfur-specific reactions, such as SN Ar sulfanylation and extended Pummerer reactions, undergo this direct arylation, offering interesting transformations that are otherwise difficult to achieve with conventional halogen-based organic synthesis.

  3. Environmentally-Safe Conditions for a Palladium-Catalyzed Direct C3-Arylation with High Turn Over Frequency of Imidazo[1,2-b]pyridazines Using Aryl Bromides and Chlorides.

    PubMed

    Chikhi, Sabah; Djebbar, Safia; Soulé, Jean-François; Doucet, Henri

    2016-09-01

    Pd(OAc)2 was found to catalyze very efficiently the direct arylation of imidazo[1,2-b]pyridazine at C3-position under a very low catalyst loading and phosphine-free conditions. The reaction can be performed in very high TOFs and TONs employing as little as 0.1-0.05 mol % catalyst using a wide range of aryl bromides. In addition, some electron-deficient aryl chlorides were also found to be suitable substrates. Moreover, 31 examples of the cross couplings were reported using green, safe, and renewable solvents, such as pentan-1-ol, diethylcarbonate or cyclopentyl methyl ether, without loss of efficiency. PMID:27380613

  4. Palladium-Catalyzed Carbonylation of β-Arylethylamide Directed by Oxalyl Amide in the Presence of Carbon Monoxide.

    PubMed

    Zhang, Li; Wang, Chao; Han, Jian; Huang, Zhi-Bin; Zhao, Yingsheng

    2016-06-17

    Pd-catalyzed regioselective coupling of β-C(sp(2))-H bonds in aromatic amines protected by oxalyl amide with carbon monoxide is reported. The reaction could tolerate various functional groups and could afford good to excellent yields of the corresponding 3,4-dihydroisoquinolinone derivatives. Remarkably, it could also tolerate β-arylethylamino acid and thiopheneethylamine derivatives, thus showing their potential for producing several important units for bioactive compound synthesis. PMID:27213988

  5. Palladium-Catalyzed Intra- and Intermolecular C–H Arylation Using Mesylates: Synthetic Scope and Mechanistic Studies

    PubMed Central

    2015-01-01

    This paper describes the development of Pd-catalyzed inter- and intramolecular direct arylation using mesylates. Furthermore, a sequential mesylation/arylation protocol using phenols as substrates is described. These transformations are general with respect to the electronics of the C–H substrates and allow for the synthesis of diverse heterocyclic motifs in good yields. Both arenes and heteroarenes efficiently participate in these reactions. Preliminary mechanistic studies are presented for both inter- and intramolecular arylations. PMID:25068072

  6. Total synthesis of resveratrol-based natural products using a palladium-catalyzed decarboxylative arylation and an oxidative Heck reaction.

    PubMed

    Klotter, Felix; Studer, Armido

    2014-02-24

    Controlled access to resveratrol-based natural products is offered by a novel, modular concept. A common building block readily available on a large scale serves as the starting material for the introduction of structurally important aryl groups by a Pd-catalyzed decarboxylative arylation and an oxidative Heck reaction with good yields and high stereoselectivity. The modular approach is convincingly documented by the successful synthesis of three racemic resveratrol-based natural products (quadrangularin A, ampelopsin D, and pallidol).

  7. Palladium Catalyzed Intermolecular Aminoacetoxylation of Alkenes and the Influence of PhI(OAc)2 on Aminopalladation Stereoselectivity

    PubMed Central

    Martínez, Claudio; Wu, Yichen; Weinstein, Adam B.; Stahl, Shannon S.; Liu, Guosheng; Muñiz, Kilian

    2013-01-01

    A modified protocol has been identified for Pd-catalyzed intermolecular aminoacetoxylation of terminal and internal alkenes that enables the alkene to be used as the limiting reagent. The results prompt a reassessment of the stereochemical course of these reactions. X-ray crystallographic characterization of two of the products, together with isotopic labeling studies, show that the amidopalladation step switches from a cis-selective process under aerobic conditions to a trans-selective process in the presence of diacetoxyiodobenzene. PMID:23734834

  8. Distal Stereocontrol Using Guanidinylated Peptides as Multifunctional Ligands: Desymmetrization of Diarylmethanes via Ullman Cross-Coupling.

    PubMed

    Kim, Byoungmoo; Chinn, Alex J; Fandrick, Daniel R; Senanayake, Chris H; Singer, Robert A; Miller, Scott J

    2016-06-29

    We report the development of a new class of guanidine-containing peptides as multifunctional ligands for transition-metal catalysis and its application in the remote desymmetrization of diarylmethanes via copper-catalyzed Ullman cross-coupling. Through design of these peptides, high levels of enantioinduction and good isolated yields were achieved in the long-range asymmetric cross-coupling (up to 93:7 er and 76% yield) between aryl bromides and malonates. Our mechanistic studies suggest that distal stereocontrol is achieved through a Cs-bridged interaction between the Lewis-basic C-terminal carboxylate of the peptides with the distal arene of the substrate. PMID:27254785

  9. Palladium-Catalyzed Oxidative N-Dealkylation/Carbonylation of Tertiary Amines with Alkynes to α,β-Alkynylamides.

    PubMed

    Mane, Rajendra S; Bhanage, Bhalchandra M

    2016-06-17

    The first highly effective Pd/C-catalyzed oxidative N-dealkylation/carbonylation of various aliphatic as well as cyclic tertiary amines with alkynes has been described. The selective sp(3) C-N bond activation of tertiary amines at the less steric side using O2 as a sole oxidant and a plausible reaction pathway for the reaction are discussed. The general and operationally simple methodology provides an alternative for the synthesis of a wide range of alk-2-ynamide derivatives under mild conditions. The present protocol is ecofriendly and practical, and it shows significant recyclability. PMID:27182623

  10. Developing Ligands for Palladium(II)-Catalyzed C–H Functionalization: Intimate Dialogue between Ligand and Substrate

    PubMed Central

    Engle, Keary M.; Yu, Jin-Quan

    2013-01-01

    Homogeneous transition metal–catalyzed reactions are indispensable to all facets of modern chemical synthesis. It is thus difficult to imagine that for much of the early 20th century, the reactivity and selectivity of all known homogeneous metal catalysts paled in comparison to their heterogeneous and biological counterparts. In the intervening decades, advances in ligand design bridged this divide, such that today some of the most demanding bond-forming events are mediated by ligand-supported homogeneous metal species. While ligand design has propelled many areas of homogeneous catalysis, in the field of Pd(II)-catalyzed C–H functionalization, suitable ligand scaffolds are lacking, which has hampered the development of broadly practical transformations based on C–H functionalization logic. In this review, we offer an account of our research employing three ligand scaffolds, mono-N-protected amino acids, 2,6-disubstituted pyridines, and 2,2′-bipyridines, to address challenges posed by several synthetically versatile substrate classes. Drawing on this work, we discuss principles of ligand design, such as the need to match a ligand to a particular substrate class, and how ligand traits such as tunability and modularity can be advantageous in reaction discovery. PMID:23565982

  11. Cross-Coupling Reactions of Aromatic and Heteroaromatic Silanolates with Aromatic and Heteroaromatic Halides

    PubMed Central

    Denmark, Scott E.; Smith, Russell C.; Chang, Wen-Tau T.; Muhuhi, Joseck M.

    2009-01-01

    The alkali-metal salts (potassium and sodium) of a large number of aryl- and heteroarylsilanols undergo efficient cross coupling with a wide range of aromatic bromides and chlorides under mild conditions to form polysubstituted biaryls. The critical feature for the success of these coupling reactions and their considerable scope is the use of bis(tri-tert-butylphosphine)palladium. Under the optimized conditions, electron-rich, electron-poor, and sterically hindered arylsilanolates afford cross-coupling products in good yields. Many functional groups are compatible with the coupling conditions such as esters, ketones, acetals, ethers, silyl ethers, and dimethylamino groups. Two particularly challenging substrates, (2-benzofuranyl)dimethylsilanolate and (2,6-dichlorophenyl)dimethylsilanolate prepared as their sodium salts showed excellent activity in the coupling reactions, in the former case also with aromatic chlorides. General methods for the efficient synthesis of a wide range of aromatic silanols are also described. PMID:19199785

  12. Suzuki-miyaura cross-coupling in acylation reactions, scope and recent developments.

    PubMed

    Blangetti, Marco; Rosso, Heléna; Prandi, Cristina; Deagostino, Annamaria; Venturello, Paolo

    2013-01-17

    Since the first report and due to its handiness and wide scope, the Suzuki-Miyaura (SM) cross coupling reaction has become a routine methodology in many laboratories worldwide. With respect to other common transition metal catalyzed cross couplings, the SM reaction has been so far less exploited as a tool to introduce an acyl function into a specific substrate. In this review, the various approaches found in the literature will be considered, starting from the direct SM acylative coupling to the recent developments of cross coupling between boronates and acyl chlorides or anhydrides. Special attention will be dedicated to the use of masked acyl boronates, alkoxy styryl and alkoxy dienyl boronates as coupling partners. A final section will be then focused on the acyl SM reaction as key synthetic step in the framework of natural products synthesis.

  13. Silicon-based cross-coupling reactions in the total synthesis of natural products.

    PubMed

    Denmark, Scott E; Liu, Jack H-C

    2010-04-12

    Unlike other variants of transition-metal-catalyzed cross-coupling reactions, those based on organosilicon donors have not been used extensively in natural product synthesis. However, recent advances such as: 1) the development of mild reaction conditions, 2) the expansion of substrate scope, 3) the development of methods to stereoselectively and efficiently introduce the silicon-containing moiety, 4) the development of a large number of sequential processes, and 5) the advent of bifunctional bis(silyl) linchpin reagents, signify the coming of age of silicon-based cross-coupling reactions. The following case studies illustrate how silicon-based cross-coupling reactions play a strategic role in constructing carbon-carbon bonds in selected target molecules.

  14. Suzuki-miyaura cross-coupling in acylation reactions, scope and recent developments.

    PubMed

    Blangetti, Marco; Rosso, Heléna; Prandi, Cristina; Deagostino, Annamaria; Venturello, Paolo

    2013-01-01

    Since the first report and due to its handiness and wide scope, the Suzuki-Miyaura (SM) cross coupling reaction has become a routine methodology in many laboratories worldwide. With respect to other common transition metal catalyzed cross couplings, the SM reaction has been so far less exploited as a tool to introduce an acyl function into a specific substrate. In this review, the various approaches found in the literature will be considered, starting from the direct SM acylative coupling to the recent developments of cross coupling between boronates and acyl chlorides or anhydrides. Special attention will be dedicated to the use of masked acyl boronates, alkoxy styryl and alkoxy dienyl boronates as coupling partners. A final section will be then focused on the acyl SM reaction as key synthetic step in the framework of natural products synthesis. PMID:23344208

  15. Exploration of new C-O electrophiles in cross-coupling reactions.

    PubMed

    Yu, Da-Gang; Li, Bi-Jie; Shi, Zhang-Jie

    2010-12-21

    Since their development in the 1970s, cross-coupling reactions catalyzed by transition metals have become one of the most important tools for constructing both carbon-carbon and carbon-heteroatom bonds. Traditionally, organohalides were widely studied and broadly used as the electrophile, both in the laboratory and in industry. Unfortunately, the high cost, environmental toxicity, and sluggish preparation often associated with aryl halides can make them undesirable for the large-scale syntheses of industrial applications. However, with the further development of catalytic systems, and particularly of the ligands contained therein, a variety of electrophiles have now been successfully applied to cross-coupling reactions. Oxygen-based electrophiles have attracted much attention due to their ready availability from phenol and carbonyl compounds. Initially, aryl and alkenyl triflates were used in cross-coupling reactions due to their high reactivity; however, low moisture stability and high cost hampered their application. Later, with the development of highly efficient catalytic systems, the less reactive sulfonates and phosphates were successfully employed in cross-coupling reactions. Although they have higher stability and can be easily prepared, low atom economy remains an obstacle to their broader utility. Our group has worked to directly apply the abundant and readily available oxygen-containing compounds, such as phenols, alcohols, ethers, and carbonyl compounds, to cross-coupling reactions. In this Account, we describe our recent efforts in transition-metal-catalyzed cross-coupling reactions of new O-based electrophiles via C-O bond activation. We began by developing the methylation of aryl methyl ethers and benzyl methyl ethers via Ni-catalyzed selective C-O bond cleavage. With the refined Ni-based catalytic system, we further applied aryl/alkenyl carboxylates and carbamates to Suzuki-Miyaura, Negishi, and Kumada-Tamao-Corriu reactions to construct various

  16. Completely N1-Selective Palladium-Catalyzed Arylation of Unsymmetric Imidazoles: Application to the Synthesis of Nilotinib

    PubMed Central

    Ueda, Satoshi; Su, Mingjuan; Buchwald, Stephen L.

    2011-01-01

    The completely N1-selective Pd-catalyzed arylation of unsymmetric imidazoles with aryl halides and triflates is described. This study showed that imidazoles have a strong inhibitory effect on the in situ formation of catalytically-active Pd(0)-ligand complex. The efficacy of the N-arylation reaction was improved drastically by the use of pre-activated solution of Pd2(dba)3 and L1. From these findings it is clear that while imidazoles can prevent binding of L1 to the Pd, once the ligand is bound to the metal, these heterocycles do not displace it. The utility of the present catalytic system was demonstrated by the regioselective synthesis of clinically important tyrosine kinase inhibitor nilotinib. PMID:22126442

  17. Syntheses and Transformations of α-Amino Acids via Palladium-Catalyzed Auxiliary-Directed sp(3) C-H Functionalization.

    PubMed

    He, Gang; Wang, Bo; Nack, William A; Chen, Gong

    2016-04-19

    α-Amino acids (αAA) are one of the most useful chiral building blocks for synthesis. There are numerous general strategies that have commonly been used for αAA synthesis, many of which employ de novo synthesis focused on enantioselective bond construction around the Cα center and others that consider conversion of existing αAA precursors carrying suitable functional groups on side chains (e.g., serine and aspartic acid). Despite significant advances in synthetic methodology, the efficient synthesis of enantiopure αAAs carrying complex side chains, as seen in numerous peptide natural products, remains challenging. Complementary to these "conventional" strategies, a strategy based on the selective functionalization of side chain C-H bonds, particularly sp(3) hybridized C-H bonds, of various readily available αAA precursors may provide a more straightforward and broadly applicable means for the synthesis and transformation of αAAs. However, many hurdles related to the low reactivity of C(sp(3))-H bonds and the difficulty of controlling selectivity must be overcome to realize the potential of C-H functionalization chemistry in this synthetic application. Over the past few years, we have carried out a systematic investigation of palladium-catalyzed bidentate auxiliary-directed C-H functionalization reactions for αAA substrates. Our strategies utilize two different types of amide-linked auxiliary groups, attached at the N or C terminus of αAA substrates, to exert complementary regio- and stereocontrol on C-H functionalization reactions through palladacycle intermediates. A variety of αAA precursors can undergo multiple modes of C(sp(3))-H functionalization, including arylation, alkenylation, alkynylation, alkylation, alkoxylation, and intramolecular aminations, at the β, γ, and even δ positions to form new αAA products with diverse structures. In addition to transforming αAAs at previously unreachable positions, these palladium-catalyzed C

  18. Suzuki-Miyaura cross-coupling of 3-pyridyl triflates with 1-alkenyl-2-pinacol boronates

    PubMed Central

    Vyvyan, James R.; Dell (née Meyer), Jennifer A.; Ligon, Toby J.; Motanic, Kelsey K.; Wall, Hayley S.

    2010-01-01

    Palladium-catalyzed Suzuki-type couplings of 3-pyridyl triflates with alkenyl pinacol boronates proceed in good to excellent yield. Optimized conditions use Pd(PPh3)4 (10 mol %) as catalyst with K3PO4 (3 equiv) as base in dioxane. PMID:21516181

  19. 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

  20. Highly Stereospecific Cross-Coupling Reactions of Anomeric Stannanes for the Synthesis of C-Aryl Glycosides.

    PubMed

    Zhu, Feng; Rourke, Michael J; Yang, Tianyi; Rodriguez, Jacob; Walczak, Maciej A

    2016-09-21

    We demonstrate that configurationally stable anomeric stannanes undergo a stereospecific cross-coupling reaction with aromatic halides in the presence of a palladium catalyst with exceptionally high levels of stereocontrol. In addition to a broad substrate scope (>40 examples), this reaction eliminates critical problems inherent to nucleophilic displacement methods and is applicable to (hetero)aromatics, peptides, pharmaceuticals, common monosaccharides, and saccharides containing free hydroxyl groups. PMID:27612008

  1. A Macroscopic Reaction: Direct Covalent Bond Formation between Materials Using a Suzuki-Miyaura Cross-Coupling Reaction

    PubMed Central

    Sekine, Tomoko; Kakuta, Takahiro; Nakamura, Takashi; Kobayashi, Yuichiro; Takashima, Yoshinori; Harada, Akira

    2014-01-01

    Cross-coupling reactions are important to form C–C covalent bonds using metal catalysts. Although many different cross-coupling reactions have been developed and applied to synthesize complex molecules or polymers (macromolecules), if cross-coupling reactions are realized in the macroscopic real world, the scope of materials should be dramatically broadened. Here, Suzuki-Miyaura coupling reactions are realized between macroscopic objects. When acrylamide gel modified with an iodophenyl group (I-gel) reacts with a gel possessing a phenylboronic group (PB-gel) using a palladium catalyst, the gels bond to form a single object. This concept can also be adapted for bonding between soft and hard materials. I-gel or PB-gel selectively bonds to the glass substrates whose surfaces are modified with an electrophile or nucleophile, respectively. PMID:25231557

  2. Chiral Ferrocenyl P,N-Ligands for Palladium-Catalyzed Asymmetric Formal [3 + 2] Cycloaddition of Propargylic Esters with β-Ketoesters: Access to Functionalized Chiral 2,3-Dihydrofurans.

    PubMed

    Zhou, Yong; Zhu, Fu-Lin; Liu, Zhen-Ting; Zhou, Xiao-Mao; Hu, Xiang-Ping

    2016-06-01

    A highly enantioselective palladium-catalyzed [3 + 2] cycloaddition of propargylic esters with β-ketoesters has been realized by employing a newly developed chiral ferrocene/benzimidazole-based P,N-ligand. This protocol features a good tolerance of functional groups in both propargylic esters and β-ketoesters, thereby delivering a variety of highly functionalized chiral 2,3-dihydrofurans bearing an exocyclic double bond at the 3-position in good yields and with high enantioselectivities (up to 98% ee). PMID:27194080

  3. Facile preparation of Pd nanoparticles supported on single-layer graphene oxide and application for the Suzuki-Miyaura cross-coupling reaction.

    PubMed

    Yamamoto, Shun-ichi; Kinoshita, Hiroshi; Hashimoto, Hideki; Nishina, Yuta

    2014-06-21

    Pd nanoparticles supported on single layer graphene oxide (Pd-slGO) were prepared by gentle heating of palladium(ii) acetate (Pd(OAc)2) and GO in ethanol that served as a mild reductant of the Pd precursor. Pd-slGO showed a high catalytic performance (TON and TOF = 237 000) in the Suzuki-Miyaura cross-coupling reaction.

  4. Ionic liquid acceleration of solid-phase suzuki-miyaura cross-coupling reactions.

    PubMed

    Revell, Jefferson D; Ganesan, A

    2002-09-01

    [reaction: see text] Room-temperature ionic liquids promote various transition metal-catalyzed reactions in the solution phase. Here, for the first time, we show that these effects are translatable to solid-phase reactions. The Suzuki-Miyaura cross-coupling of 4-iodophenol immobilized on polystyrene-Wang resin with various arylboronic acids was significantly accelerated by the ionic liquid 1-butyl-3-methylimidazolium tetrafluoroborate ([bmim][BF(4)(-)]).

  5. Palladium-Catalyzed C-H Arylation of α,β-Unsaturated Imines: Catalyst-Controlled Synthesis of Enamine and Allylic Amine Derivatives.

    PubMed

    Li, Minyan; González-Esguevillas, María; Berritt, Simon; Yang, Xiaodong; Bellomo, Ana; Walsh, Patrick J

    2016-02-18

    A unique chemo- and regioselective α- and γ-arylation of palladium azapentadienyl intermediates is presented. Two distinct catalysts and sets of conditions successfully controlled the regioselectivity of the arylation. These methods provide the first umpolung C-H functionalization of azapentadienyl palladium intermediates and enable the divergent synthesis of allylic amine and enamine derivatives, which are of significant interest in the pharmaceutical industry. PMID:26846375

  6. Integrated cross-coupling strategy for an α-carboline-based Aurora B kinase inhibitor.

    PubMed

    Mineno, Masahiro; Sera, Misayo; Ueda, Tsuyoshi; Mizufune, Hideya; Zanka, Atsuhiko; O'Bryan, Colin; Brown, Jason; Scorah, Nick

    2015-02-01

    An efficient and practical synthetic process for an α-carboline-based Aurora B kinase inhibitor was achieved using an integrated Pd-catalyzed cross-coupling strategy. The process features a mild and efficient method for construction of the α-carboline core by employing a Pd-catalyzed sequence of Buchwald-Hartwig amination and intramolecular direct C-H arylation at the ortho position of an unsubstituted aniline moiety, which is a key functionality for further derivatization with a Suzuki coupling via Sandmeyer iodination. The process has eliminated expensive starting materials and column chromatography purifications and enabled considerable enhancement of the total yield from 11% to 48%.

  7. Unparalleled Ease of Access to a Library of Biheteroaryl Fluorophores via Oxidative Cross-Coupling Reactions: Discovery of Photostable NIR Probe for Mitochondria.

    PubMed

    Cheng, Yangyang; Li, Gaocan; Liu, Yang; Shi, Yang; Gao, Ge; Wu, Di; Lan, Jingbo; You, Jingsong

    2016-04-13

    The development of straightforward accesses to organic functional materials through C-H activation is a revolutionary trend in organic synthesis. In this article, we propose a concise strategy to construct a large library of donor-acceptor-type biheteroaryl fluorophores via the palladium-catalyzed oxidative C-H/C-H cross-coupling of electron-deficient 2H-indazoles with electron-rich heteroarenes. The directly coupled biheteroaryl fluorophores, named Indazo-Fluors, exhibit continuously tunable full-color emissions with quantum yields up to 93% and large Stokes shifts up to 8705 cm(-1) in CH2Cl2. By further fine-tuning of the substituent on the core skeleton, Indazo-Fluor 3l (FW = 274; λem = 725 nm) is obtained as the lowest molecular weight near-infrared (NIR) fluorophore with emission wavelength over 720 nm in the solid state. The NIR dye 5h specifically lights up mitochondria in living cells with bright red luminescence. Typically, commercially available mitochondria trackers suffer from poor photostability. Indazo-Fluor 5h exhibits superior photostability and very low cytotoxicity, which would be a prominent reagent for in vivo mitochondria imaging. PMID:26854564

  8. Surface oxygen triggered size change of palladium nano-crystals impedes catalytic efficacy.

    PubMed

    Zou, Jianli; Stewart, Scott G; Raston, Colin L; Iyer, K Swaminathan

    2011-02-14

    Palladium nano-crystals increase in size during the initial recycling in Heck cross coupling reactions. We demonstrate that oxygen adsorbed on the surface of palladium nano-crystals plays a pivotal role in driving the ripening. This in turn is associated with a loss in catalytic activity.

  9. One-shot access to α,β-difunctionalized azepenes and dehydropiperidines by reductive cross-coupling of α-selenonyl-β-selenyl enamides with organic bromides.

    PubMed

    Beng, Timothy K; Silaire, Ann Wens V; Alwali, Amir; Bassler, Daniel P

    2015-08-01

    The synthesis of α- and α,β-functionalized azepenes and dehydropiperidines from readily prepared α-selenonyl eneformamides or enecarbamates has been achieved through Fe-catalyzed α-substitutive deselenonation, β-regioselective lithiation/trapping, and Co-catalyzed reductive cross-coupling protocols.

  10. Palladium-catalyzed Reppe carbonylation.

    PubMed

    Kiss, G

    2001-11-01

    PdX2L2/L/HA (A = weakly coordinating anion, L = phosphine) complexes are active catalysts in the hydroesterification of alkenes, alkynes, and conjugated dienes. Shell, the only major corporate player in the field, recently developed two very active catalyst systems tailored to the hydroesterification of either alkenes or alkynes. The hydroesterification of propyne with their Pd(OAc)2/PN/HA (PN = (2-pyridyl)diphenylphosphine, HA = strong acid with weakly coordinating anion, like methanesulfonic acid) catalyst has been declared commercially ready. However, despite the significant progress in the activity of Pd-hydroesterification catalysts, further improvements are warranted. Thus, for example, activity maintenance still seems to be an issue. Homogeneous Pd catalysts are prone to a number of deactivation reactions. Activity and stability promoters are often corrosive and add to the complexity of the system, making it less attractive. Nonetheless, the versatility of the process and its tolerance toward the functional groups of substrates should appeal especially to the makers of specialty products. Although hydroesterification yields esters from alkenes, alkynes, and dienes in fewer steps than hydroformylation does, the latter has some advantages at the current state of the art. (1) Hydroformylation catalysts, particularly some recently published phosphine-modified Rh systems, can achieve very high regioselectivity for the linear product that hydroesterification catalysts cannot match yet. By analogy with hydroformylation, bulkier ligands ought to be tested in hydroesterification to increase normal-ester selectivity. (2) Hydroformylation is proven, commercial. Hydroesterification can only replace it if it can provide significant economic incentives. Similar or just marginally better performance could not justify the cost of development of a new technology. (3) Hydroesterification requires pure CO while hydroformylation uses syngas, a mixture of CO and H2. The latter is typically more available and less expensive (for industrial applications CO is most often separated from syngas). (4) The acid component of the hydroesterification catalyst makes the process corrosive. It would be desirable to develop new hydroesterification catalysts that do not require acid stabilizer/activity booster. Clearly, any new hydroesterification technology will directly compete with the hydroformylation route. This is especially true for olefin feeds, since both processes add one CO to the olefin, yielding oxygenates that can be converted into identical products. For some niche applications, like the production of MMA from propyne, hydroesterification seems to have an advantage as compared to hydroformylation due to the high activity and selectivity of the Pd(OAc)2/(2-pyridyl)diphenylphosphine catalyst. Since hydroesterification is an emerging technology, it is reasonable to assume that the potential for improvement is greater than in the mature hydroformylation. It is therefore possible that hydroesterification will become competitive in the future; thus, continued effort in the field is warranted.

  11. An efficient protocol for the stereoselective construction of multisubstituted fluorine-containing alkenes. A palladium-catalyzed bisstannylation of fluorinated internal alkynes.

    PubMed

    Konno, Tsutomu; Kinugawa, Ryoko; Morigaki, Atsunori; Ishihara, Takashi

    2009-11-01

    On treatment of various fluorinated internal alkynes with 1.2 equiv of hexabutylditin under the influence of 2.5 mol % of Pd(t-BuNC)(2)Cl(2) in THF at room temperature for 4 h, the bisstannylation proceeded smoothly to afford the corresponding bisstannylated cis-adducts in high yields. Thus obtained adducts were subjected to the Stille cross-coupling reaction to give the corresponding tetrasubstituted fluorine-containing alkenes with defined stereochemistry in good yields.

  12. Microwave-assisted C-C bond forming cross-coupling reactions: an overview.

    PubMed

    Mehta, Vaibhav P; Van der Eycken, Erik V

    2011-10-01

    Among the fundamental transformations in the field of synthetic organic chemistry, transition-metal-catalyzed reactions provide some of the most attractive methodologies for the formation of C-C and C-heteroatom bonds. As a result, the application of these reactions has increased tremendously during the past decades and cross-coupling reactions became a standard tool for synthetic organic chemists. Furthermore, a tremendous upsurge in the development of new catalysts and ligands, as well as an increased understanding of the mechanisms, has contributed substantially to recent advances in the field. Traditionally, organic reactions are carried out by conductive heating with an external heat source (for example, an oil bath). However, the application of microwave irradiation is a steadily gaining field as an alternative heating mode since its dawn at the end of the last century. This tutorial review focuses on some of the recent developments in the field of cross-coupling reactions assisted by microwave irradiation.

  13. Palladium-Catalyzed Intermolecular Controlled Insertion of Benzyne-Benzyne-Alkene and Benzyne-Alkyne-Alkene-Synthesis of Phenanthrene and Naphthalene Derivatives.

    PubMed

    Yoshikawa; Yamamoto

    2000-01-01

    Aryne reagents, unlike alkynes, undergo insertion by allyl palladium complexes. The verification of the conversion described here is shown using Equation (1) as an example. The reaction proceeds in a few hours in refluxing acetonitrile to give the phenanthrene derivative in up to 71 % yield.

  14. Iron-mediated inter- and intramolecular reductive cross-coupling of unactivated alkyl chlorides with aryl bromides.

    PubMed

    Li, Zhuang; Sun, Hong-Mei; Shen, Qi

    2016-03-28

    An efficient one-pot intermolecular reductive cross-coupling of unactivated primary and secondary alkyl chlorides bearing β-hydrogens with aryl bromides is described. A combination of magnesium turnings and a catalytic amount of the commercially available iron(iii) complex Fe(PPh3)2Cl3 was used, and the conditions were also successfully extended to an intramolecular reaction for the first time. Both types of cross-coupling reactions proceed under mild conditions, involving the in situ generation of aryl Grignard reagents, and show good applicability to a variety of readily available unactivated alkyl chlorides, which have previously been challenging substrates in iron-catalyzed reductive cross-coupling reactions. PMID:26940697

  15. Palladium-catalyzed synthesis of ammonium sulfinates from aryl halides and a sulfur dioxide surrogate: a gas- and reductant-free process.

    PubMed

    Emmett, Edward J; Hayter, Barry R; Willis, Michael C

    2014-09-15

    Sulfonyl-derived functional groups populate a broad range of useful molecules and materials, and despite a variety of preparative methods being available, processes which introduce the most basic sulfonyl building block, sulfur dioxide, using catalytic methods, are rare. Described herein is a simple reaction system consisting of the sulfur dioxide surrogate DABSO, triethylamine, and a palladium(0) catalyst for effective convertion of a broad range of aryl and heteroaryl halides into the corresponding ammonium sulfinates. Key features of this gas- and reductant-free reaction include the low loadings of palladium (1 mol%) and ligand (1.5 mol%) which can be employed, and the use of isopropyl alcohol as both a solvent and formal reductant. The ammonium sulfinate products are converted in situ into a variety of sulfonyl-containing functional groups, including sulfones, sulfonyl chlorides, and sulfonamides.

  16. Multimetallic catalysed cross-coupling of aryl bromides with aryl triflates

    NASA Astrophysics Data System (ADS)

    Ackerman, Laura K. G.; Lovell, Matthew M.; Weix, Daniel J.

    2015-08-01

    The advent of transition-metal catalysed strategies for forming new carbon-carbon bonds has revolutionized the field of organic chemistry, enabling the efficient synthesis of ligands, materials, and biologically active molecules. In cases where a single metal fails to promote a selective or efficient transformation, the synergistic cooperation of two distinct catalysts--multimetallic catalysis--can be used instead. Many important reactions rely on multimetallic catalysis, such as the Wacker oxidation of olefins and the Sonogashira coupling of alkynes with aryl halides, but this approach has largely been limited to the use of metals with distinct reactivities, with only one metal catalyst undergoing oxidative addition. Here, we demonstrate that cooperativity between two group 10 metal catalysts--(bipyridine)nickel and (1,3-bis(diphenylphosphino)propane)palladium--enables a general cross-Ullmann reaction (the cross-coupling of two different aryl electrophiles). Our method couples aryl bromides with aryl triflates directly, eliminating the use of arylmetal reagents and avoiding the challenge of differentiating between multiple carbon-hydrogen bonds that is required for direct arylation methods. Selectivity can be achieved without an excess of either substrate and originates from the orthogonal reactivity of the two catalysts and the relative stability of the two arylmetal intermediates. While (1,3-bis(diphenylphosphino)propane)palladium reacts preferentially with aryl triflates to afford a persistent intermediate, (bipyridine)nickel reacts preferentially with aryl bromides to form a transient, reactive intermediate. Although each catalyst forms less than 5 per cent cross-coupled product in isolation, together they are able to achieve a yield of up to 94 per cent. Our results reveal a new method for the synthesis of biaryls, heteroaryls, and dienes, as well as a general mechanism for the selective transfer of ligands between two metal catalysts. We anticipate that this

  17. Stereodivergent hydrogermylations of α-trifluoromethylated alkynes and their applications in cross-coupling reactions.

    PubMed

    Schweizer, Stéphane; Tresse, Cédric; Bisseret, Philippe; Lalevée, Jacques; Evano, Gwilherm; Blanchard, Nicolas

    2015-04-01

    The hydrometalation of alkynes with group 14 elements such as tin- or silyl hydrides is a classical transformation in organic synthesis. Strangely, among the group 14 elements, the use of germanium hydrides is rarely seen. Two efficient, stereodivergent, and broadly applicable routes to (Z)- and (E)-α-CF3-vinylgermanes by regio- and stereoselective hydrogermylation of α-trifluoromethylated alkynes under radical or transition-metal-catalyzed conditions are reported. Furthermore, we demonstrate that the resulting stereodefined fluorinated building blocks are remarkable cross-coupling partners, provided that the vinylgermane is appropriately tuned electronically, as demonstrated by the synthesis of trisubstituted (Z)- and (E)-α-trifluoromethylated alkenes.

  18. Direct Synthesis of Polyaryls by Consecutive Oxidative Cross-Coupling of Phenols with Arenes.

    PubMed

    Dyadyuk, Alina; Sudheendran, Kavitha; Vainer, Yulia; Vershinin, Vlada; Shames, Alexander I; Pappo, Doron

    2016-09-01

    A bioinspired iron-catalyzed consecutive oxidative cross-coupling reaction between a single phenolic unit and nucleophilic arenes was developed. This sustainable transformation offers a selective synthetic strategy for the preparation of complex polyaryl compounds directly from readily available phenols. With the aid of electron paramagnetic resonance spectroscopy, it was demonstrated that the groups ortho to the phenolic functionality (whether hydrogen, methyl, or methoxy) direct the regioselectivity (ortho, para, or meta via dienone-phenol rearrangement) and chemoselectivity (C-C coupling or C-O coupling) in this multistep process. PMID:27529128

  19. 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. PMID:26507477

  20. Metallaphotoredox-catalysed sp(3)-sp(3) cross-coupling of carboxylic acids with alkyl halides.

    PubMed

    Johnston, Craig P; Smith, Russell T; Allmendinger, Simon; MacMillan, David W C

    2016-08-18

    In the past 50 years, cross-coupling reactions mediated by transition metals have changed the way in which complex organic molecules are synthesized. The predictable and chemoselective nature of these transformations has led to their widespread adoption across many areas of chemical research. However, the construction of a bond between two sp(3)-hybridized carbon atoms, a fundamental unit of organic chemistry, remains an important yet elusive objective for engineering cross-coupling reactions. In comparison to related procedures with sp(2)-hybridized species, the development of methods for sp(3)-sp(3) bond formation via transition metal catalysis has been hampered historically by deleterious side-reactions, such as β-hydride elimination with palladium catalysis or the reluctance of alkyl halides to undergo oxidative addition. To address this issue, nickel-catalysed cross-coupling processes can be used to form sp(3)-sp(3) bonds that utilize organometallic nucleophiles and alkyl electrophiles. In particular, the coupling of alkyl halides with pre-generated organozinc, Grignard and organoborane species has been used to furnish diverse molecular structures. However, the manipulations required to produce these activated structures is inefficient, leading to poor step- and atom-economies. Moreover, the operational difficulties associated with making and using these reactive coupling partners, and preserving them through a synthetic sequence, has hindered their widespread adoption. A generically useful sp(3)-sp(3) coupling technology that uses bench-stable, native organic functional groups, without the need for pre-functionalization or substrate derivatization, would therefore be valuable. Here we demonstrate that the synergistic merger of photoredox and nickel catalysis enables the direct formation of sp(3)-sp(3) bonds using only simple carboxylic acids and alkyl halides as the nucleophilic and electrophilic coupling partners, respectively. This metallaphotoredox

  1. Metallaphotoredox-catalysed sp(3)-sp(3) cross-coupling of carboxylic acids with alkyl halides.

    PubMed

    Johnston, Craig P; Smith, Russell T; Allmendinger, Simon; MacMillan, David W C

    2016-08-18

    In the past 50 years, cross-coupling reactions mediated by transition metals have changed the way in which complex organic molecules are synthesized. The predictable and chemoselective nature of these transformations has led to their widespread adoption across many areas of chemical research. However, the construction of a bond between two sp(3)-hybridized carbon atoms, a fundamental unit of organic chemistry, remains an important yet elusive objective for engineering cross-coupling reactions. In comparison to related procedures with sp(2)-hybridized species, the development of methods for sp(3)-sp(3) bond formation via transition metal catalysis has been hampered historically by deleterious side-reactions, such as β-hydride elimination with palladium catalysis or the reluctance of alkyl halides to undergo oxidative addition. To address this issue, nickel-catalysed cross-coupling processes can be used to form sp(3)-sp(3) bonds that utilize organometallic nucleophiles and alkyl electrophiles. In particular, the coupling of alkyl halides with pre-generated organozinc, Grignard and organoborane species has been used to furnish diverse molecular structures. However, the manipulations required to produce these activated structures is inefficient, leading to poor step- and atom-economies. Moreover, the operational difficulties associated with making and using these reactive coupling partners, and preserving them through a synthetic sequence, has hindered their widespread adoption. A generically useful sp(3)-sp(3) coupling technology that uses bench-stable, native organic functional groups, without the need for pre-functionalization or substrate derivatization, would therefore be valuable. Here we demonstrate that the synergistic merger of photoredox and nickel catalysis enables the direct formation of sp(3)-sp(3) bonds using only simple carboxylic acids and alkyl halides as the nucleophilic and electrophilic coupling partners, respectively. This metallaphotoredox

  2. Metallaphotoredox-catalysed sp3-sp3 cross-coupling of carboxylic acids with alkyl halides

    NASA Astrophysics Data System (ADS)

    Johnston, Craig P.; Smith, Russell T.; Allmendinger, Simon; MacMillan, David W. C.

    2016-08-01

    In the past 50 years, cross-coupling reactions mediated by transition metals have changed the way in which complex organic molecules are synthesized. The predictable and chemoselective nature of these transformations has led to their widespread adoption across many areas of chemical research. However, the construction of a bond between two sp3-hybridized carbon atoms, a fundamental unit of organic chemistry, remains an important yet elusive objective for engineering cross-coupling reactions. In comparison to related procedures with sp2-hybridized species, the development of methods for sp3-sp3 bond formation via transition metal catalysis has been hampered historically by deleterious side-reactions, such as β-hydride elimination with palladium catalysis or the reluctance of alkyl halides to undergo oxidative addition. To address this issue, nickel-catalysed cross-coupling processes can be used to form sp3-sp3 bonds that utilize organometallic nucleophiles and alkyl electrophiles. In particular, the coupling of alkyl halides with pre-generated organozinc, Grignard and organoborane species has been used to furnish diverse molecular structures. However, the manipulations required to produce these activated structures is inefficient, leading to poor step- and atom-economies. Moreover, the operational difficulties associated with making and using these reactive coupling partners, and preserving them through a synthetic sequence, has hindered their widespread adoption. A generically useful sp3-sp3 coupling technology that uses bench-stable, native organic functional groups, without the need for pre-functionalization or substrate derivatization, would therefore be valuable. Here we demonstrate that the synergistic merger of photoredox and nickel catalysis enables the direct formation of sp3-sp3 bonds using only simple carboxylic acids and alkyl halides as the nucleophilic and electrophilic coupling partners, respectively. This metallaphotoredox protocol is suitable for

  3. Asymmetric synthesis of chiral β-alkynyl carbonyl and sulfonyl derivatives via sequential palladium and copper catalysis† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c6sc01724j Click here for additional data file.

    PubMed Central

    Masters, James T.; Taft, Benjamin R.; Lumb, Jean-Philip

    2016-01-01

    We present a full account detailing the development of a sequential catalysis strategy for the synthesis of chiral β-alkynyl carbonyl and sulfonyl derivatives. A palladium-catalyzed cross coupling of terminal alkyne donors with acetylenic ester, ketone, and sulfone acceptors generates stereodefined enynes in high yield. These compounds are engaged in an unprecedented, regio- and enantioselective copper-catalyzed conjugate reduction. The process exhibits a high functional group tolerance, and this enables the synthesis of a broad range of chiral products from simple, readily available alkyne precursors. The utility of the method is demonstrated through the elaboration of the chiral β-alkynyl products into a variety of different molecular scaffolds. Its value in complex molecule synthesis is further validated through a concise, enantioselective synthesis of AMG 837, a potent GPR40 receptor agonist. PMID:27746892

  4. Highly Efficient and Selective Synthesis of Conjugated Triynes and Higher Oligoynes of Biological and Materials Chemical Interest via Palladium-Catalyzed Alkynyl-Alkenyl Coupling†

    PubMed Central

    Métay, Estelle; Hu, Qian

    2013-01-01

    Iteration of Pd-catalyzed reaction of alkynyl- and oligoynylzincs with (E)-ICH=CHCl followed by metalation-termination with electrophiles(E) has provided a linear route to conjugated tri- and tetraynes, while Pd-catalyzed monoalkynylation of 1,1-dibromoenynes accompanied by dehydrobromination has provided a convergent route to conjugated tri-, tetra-, and pentaynes. Both display unprecedent high efficiency and selectivity. PMID:17134269

  5. Direct catalytic cross-coupling of organolithium compounds

    NASA Astrophysics Data System (ADS)

    Giannerini, Massimo; Fañanás-Mastral, Martín; Feringa, Ben L.

    2013-08-01

    Catalytic carbon-carbon bond formation based on cross-coupling reactions plays a central role in the production of natural products, pharmaceuticals, agrochemicals and organic materials. Coupling reactions of a variety of organometallic reagents and organic halides have changed the face of modern synthetic chemistry. However, the high reactivity and poor selectivity of common organolithium reagents have largely prohibited their use as a viable partner in direct catalytic cross-coupling. Here we report that in the presence of a Pd-phosphine catalyst, a wide range of alkyl-, aryl- and heteroaryl-lithium reagents undergo selective cross-coupling with aryl- and alkenyl-bromides. The process proceeds quickly under mild conditions (room temperature) and avoids the notorious lithium halogen exchange and homocoupling. The preparation of key alkyl-, aryl- and heterobiaryl intermediates reported here highlights the potential of these cross-coupling reactions for medicinal chemistry and material science.

  6. Ordered Mesoporous Polymers for Biomass Conversions and Cross-Coupling Reactions.

    PubMed

    Liu, Fujian; Wu, Qin; Liu, Chen; Qi, Chenze; Huang, Kuan; Zheng, Anmin; Dai, Sheng

    2016-09-01

    Amino group-functionalized, ordered mesoporous polymers (OMP-NH2 ) were prepared using a solvent-free synthesis by grinding mixtures of solid raw precursors (aminophenol, terephthaldehyde), using block copolymer templates, and curing at 140-180 °C. OMP-NH2 was functionalized with acidic sites and incorporated with palladium, giving multifunctional solid catalysts with large Brunauer-Emmett-Teller (BET) surface areas, abundant and ordered mesopores, good thermal stabilities, controllable concentrations, and good dispersion of active centers. The resultant solid catalysts showed excellent catalytic activities and good reusability in biomass conversions and cross-coupling reactions-much superior to those of various reported solid catalysts such as Amberlyst 15, SBA-15-SO3 H, and Pd/C and comparable to those of homogeneous catalysts such as heteropoly acid, HCl, and palladium acetate. A facile green approach was developed for the synthesis of ordered mesoporous polymeric solid catalysts with excellent activities for conversion of low-cost feedstocks into useful chemicals and clean biofuels. PMID:27529676

  7. Tetrahydroxydiboron-Mediated Palladium-Catalyzed Transfer Hydrogenation and Deuteriation of Alkenes and Alkynes Using Water as the Stoichiometric H or D Atom Donor.

    PubMed

    Cummings, Steven P; Le, Thanh-Ngoc; Fernandez, Gilberto E; Quiambao, Lorenzo G; Stokes, Benjamin J

    2016-05-18

    There are few examples of catalytic transfer hydrogenations of simple alkenes and alkynes that use water as a stoichiometric H or D atom donor. We have found that diboron reagents efficiently mediate the transfer of H or D atoms from water directly onto unsaturated C-C bonds using a palladium catalyst. This reaction is conducted on a broad variety of alkenes and alkynes at ambient temperature, and boric acid is the sole byproduct. Mechanistic experiments suggest that this reaction is made possible by a hydrogen atom transfer from water that generates a Pd-hydride intermediate. Importantly, complete deuterium incorporation from stoichiometric D2O has also been achieved. PMID:27135185

  8. Palladium(II)-Catalyzed Annulation between ortho-Alkenylphenols and Allenes. Key Role of the Metal Geometry in Determining the Reaction Outcome

    PubMed Central

    2016-01-01

    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. PMID:27807509

  9. Coriolis cross-coupling effects: disorienting and nauseogenic or not?

    PubMed

    Guedry, F E; Benson, A J

    1978-01-01

    Nausea and disorientation are sometimes produced by head movements during turning maneuvers in aircraft. These responses are usually attributed to Coriolis cross-coupling stimulation of the vestibular system, although it has been indicated recently that many turning maneuvers of aircraft have insufficient angular velocity to generate such effects. The purpose of the present study was to further distinguish conditions in which Coriolis cross-coupling effects are disorienting and nauseogenic from conditions in which they are neither.

  10. Review on palladium-containing perovskites: synthesis, physico-chemical properties and applications in catalysis.

    PubMed

    Essoumhi, Abdellatif; El Kazzouli, Saïd; Bousmina, Mosto

    2014-02-01

    This review reports on the recent advances in the synthesis and physico-chemical properties of palladium-containing perovskites. Initially, the perovskite structure is briefly reviewed, then palladium-containing perovskites synthesis and physico-chemical properties are detailed. The applications of palladium-containing perovskites in catalysis; namely, NO reduction, methane combustion, methanol as well as ethanol oxidation, are briefly highlighted. The involvement and the important contribution of palladium-containing perovskites in cross-coupling reactions, especially Suzuki-Miyaura, Sonogashira, Ulmann and Grignard, are discussed. PMID:24749470

  11. Stereospecific cross-coupling reactions of aryl-substituted tetrahydrofurans, tetrahydropyrans, and lactones.

    PubMed

    Tollefson, Emily J; Dawson, David D; Osborne, Charlotte A; Jarvo, Elizabeth R

    2014-10-22

    The stereospecific ring-opening of O-heterocycles to provide acyclic alcohols and carboxylic acids with controlled formation of a new C-C bond is reported. These reactions provide new methods for synthesis of acyclic polyketide analogs with complex stereochemical arrays. Stereoselective synthesis of the cyclic template is utilized to control relative configuration; subsequent stereospecific nickel-catalyzed ring-opening affords the acyclic product. Aryl-substituted tetrahydrofurans and tetrahydropyrans undergo nickel-catalyzed Kumada-type coupling with a range of Grignard reagents to furnish acyclic alcohols with high diastereoselectivity. Enantioenriched lactones undergo Negishi-type cross-coupling with dimethylzinc to afford enantioenriched carboxylic acids. Application in a two-step enantioselective synthesis of an anti-dyslipidemia agent is demonstrated. PMID:25308512

  12. Scalable production of Cu@C composites for cross-coupling catalysis

    SciTech Connect

    Bu, Lijuan; Ming, Hai

    2015-10-15

    Highlights: • Cu@C core–shell composite was prepared by reduction of [Cu(NH{sub 3}){sub 4}]{sup 2+} with glucose. • The carbon shell in Cu@C can be tuned to the different degree of carbonization. • The Cu@C composites were utilized to catalyze the C−N cross coupling reaction. • The catalytic ability of Cu@C depends on the degree of shell-carbonization. - Abstract: A novel Cu@C core–shell microstructure was prepared by reduction of [Cu(NH{sub 3}){sub 4}]{sup 2+} with glucose using a mild hydrothermal process. The carbon shell of such Cu@C composite can be tuned to different carbonization degrees just through varying the calcination conditions. The structural properties of as-prepared Cu@C were investigated in detail by scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), transmission electron micrographs (TEM) and Raman spectra. In addition, these Cu@C composites were firstly used to catalyze the C−N cross coupling of amines with iodobenzene. Among them, the catalytic ability of Cu@C composites increased as their surface carbon’s carburization degree improved.

  13. Palladium(II) Catalyzed Cyclization-Carbonylation-Cyclization Coupling Reaction of (ortho-Alkynyl Phenyl) (Methoxymethyl) Sulfides Using Molecular Oxygen as the Terminal Oxidant.

    PubMed

    Shen, Rong; Kusakabe, Taichi; Yatsu, Tomofumi; Kanno, Yuichiro; Takahashi, Keisuke; Nemoto, Kiyomitsu; Kato, Keisuke

    2016-01-01

    An efficient Pd(II)/Pd⁰-p-benzoquinone/hydroquinone-CuCl₂/CuCl catalyst system was developed that uses environmentally friendly molecular oxygen as the terminal oxidant to catalyze the cyclization-carbonylation-cyclization coupling reaction (CCC-coupling reaction) of (o-alkynyl phenyl) (methoxymethyl) sulfides. PMID:27607997

  14. Palladium(II) Catalyzed Cyclization-Carbonylation-Cyclization Coupling Reaction of (ortho-Alkynyl Phenyl) (Methoxymethyl) Sulfides Using Molecular Oxygen as the Terminal Oxidant.

    PubMed

    Shen, Rong; Kusakabe, Taichi; Yatsu, Tomofumi; Kanno, Yuichiro; Takahashi, Keisuke; Nemoto, Kiyomitsu; Kato, Keisuke

    2016-09-05

    An efficient Pd(II)/Pd⁰-p-benzoquinone/hydroquinone-CuCl₂/CuCl catalyst system was developed that uses environmentally friendly molecular oxygen as the terminal oxidant to catalyze the cyclization-carbonylation-cyclization coupling reaction (CCC-coupling reaction) of (o-alkynyl phenyl) (methoxymethyl) sulfides.

  15. A new color of the synthetic chameleon methoxyallene: synthesis of trifluoromethyl-substituted pyridinol derivatives: an unusual reaction mechanism, a remarkable crystal packing, and first palladium-catalyzed coupling reactions.

    PubMed

    Flögel, Oliver; Dash, Jyotirmayee; Brüdgam, Irene; Hartl, Hans; Reissig, Hans-Ulrich

    2004-09-01

    Addition of lithiated methoxyallene to pivalonitrile afforded after aqueous workup the expected iminoallene 1 in excellent yield. Treatment of this intermediate with silver nitrate accomplished the desired cyclization to the electron-rich pyrrole derivative 2 in moderate yield. Surprisingly, trifluoroacetic acid converted iminoallene 1 to a mixture of enamide 3 and trifluoromethyl-substituted pyridinol 4 (together with its tautomer 5). A plausible mechanism proposed for this intriguing transformation involves addition of trifluoroacetate to the central allene carbon atom of an allenyl iminium intermediate as crucial step. Enamide 3 is converted to pyridinol 4 by an intramolecular aldol-type process. A practical direct synthesis of trifluoromethyl-substituted pyridinols 4, 10, 11, and 12 starting from typical nitriles and methoxyallene was established. Pyridinol 10 shows an interesting crystal packing with three molecules in the elementary cell and a remarkable helical supramolecular arrangement. Trifluoromethyl-substituted pyridinol 4 was converted to the corresponding pyridyl nonaflate 13, which is an excellent precursor for palladium-catalyzed reactions leading to pyridine derivatives 14-16 in good to excellent yields. The new synthesis of trifluoromethyl-substituted pyridines disclosed here demonstrates a novel reactivity pattern of lithiated methoxyallene which is incorporated into the products as the unusual tripolar synthon B. PMID:15352110

  16. A new color of the synthetic chameleon methoxyallene: synthesis of trifluoromethyl-substituted pyridinol derivatives: an unusual reaction mechanism, a remarkable crystal packing, and first palladium-catalyzed coupling reactions.

    PubMed

    Flögel, Oliver; Dash, Jyotirmayee; Brüdgam, Irene; Hartl, Hans; Reissig, Hans-Ulrich

    2004-09-01

    Addition of lithiated methoxyallene to pivalonitrile afforded after aqueous workup the expected iminoallene 1 in excellent yield. Treatment of this intermediate with silver nitrate accomplished the desired cyclization to the electron-rich pyrrole derivative 2 in moderate yield. Surprisingly, trifluoroacetic acid converted iminoallene 1 to a mixture of enamide 3 and trifluoromethyl-substituted pyridinol 4 (together with its tautomer 5). A plausible mechanism proposed for this intriguing transformation involves addition of trifluoroacetate to the central allene carbon atom of an allenyl iminium intermediate as crucial step. Enamide 3 is converted to pyridinol 4 by an intramolecular aldol-type process. A practical direct synthesis of trifluoromethyl-substituted pyridinols 4, 10, 11, and 12 starting from typical nitriles and methoxyallene was established. Pyridinol 10 shows an interesting crystal packing with three molecules in the elementary cell and a remarkable helical supramolecular arrangement. Trifluoromethyl-substituted pyridinol 4 was converted to the corresponding pyridyl nonaflate 13, which is an excellent precursor for palladium-catalyzed reactions leading to pyridine derivatives 14-16 in good to excellent yields. The new synthesis of trifluoromethyl-substituted pyridines disclosed here demonstrates a novel reactivity pattern of lithiated methoxyallene which is incorporated into the products as the unusual tripolar synthon B.

  17. Microstructure-stability relations studies of porous chitosan microspheres supported palladium catalysts.

    PubMed

    Zeng, Minfeng; Zhang, Xin; Qi, Chenze; Zhang, Xian-Man

    2012-12-01

    In this study, polyethylene glycol (PEG) with different molecular weight, polyvinyl pyrrolidone (PVP), and polyvinyl alcohol (PVA), are chosen as porogens for preparing chitosan base porous microsphere supported palladium catalyst for coupling reactions. The pore structure of the microspheres was controlled by the compatibility of chitosan and counterpart polymers. The prepared porous chitosan microspheres supported palladium heterogeneous catalysts have been evaluated using the well-established Ullmann reductive homocoupling and the Heck cross-coupling reactions. The activities, stabilities and recyclability of the porous chitosan microspheres supported palladium catalysts are not only highly dependent upon the surface areas of the solid supports, but also upon the chemical properties of the water-soluble polymers. The degradation of the prepared heterogeneous palladium catalysts is mainly caused by a combination of the palladium leaching and the morphological transformation of the palladium species from the amorphous into the crystals.

  18. A general synthesis of alkenyl-substituted benzofurans, indoles, and isoquinolones by cascade palladium-catalyzed heterocyclization/oxidative Heck coupling.

    PubMed

    Alvarez, Rosana; Martínez, Claudio; Madich, Youssef; Denis, J Gabriel; Aurrecoechea, José M; de Lera, Angel R

    2010-11-01

    Structurally diverse C3-alkenylbenzofurans, C3-alkenylindoles, and C4-alkenylisoquinolones are efficiently prepared by using consecutive Sonogashira and cascade Pd-catalyzed heterocyclization/oxidative Heck couplings from readily available ortho-iodosubstituted phenol, aniline, and benzamide substrates, alkynes, and functionalized olefins. The cyclization of O- and N-heteronucleophiles follows regioselective 5-endo-dig- or 6-endo-dig-cyclization modes, whereas the subsequent Heck-type coupling with both mono- and disubstituted olefins takes place stereoselectively with exclusive formation of the E isomers in most cases.

  19. Application of a Palladium-Catalyzed C-H Functionalization/Indolization Method to Syntheses of cis-Trikentrin A and Herbindole B.

    PubMed

    Leal, Raul A; Bischof, Caroline; Lee, Youjin V; Sawano, Shota; McAtee, Christopher C; Latimer, Luke N; Russ, Zachary N; Dueber, John E; Yu, Jin-Quan; Sarpong, Richmond

    2016-09-19

    We describe herein formal syntheses of the indole alkaloids cis-trikentrin A and herbindole B from a common meso-hydroquinone intermediate prepared by a ruthenium-catalyzed [2+2+1+1] cycloaddition that has not been used previously in natural product synthesis. Key steps include a sterically demanding Buchwald-Hartwig amination as well as a unique C(sp(3) )-H amination/indole formation. Studies toward a selective desymmetrization of the meso-hydroquinone are also reported. PMID:27570932

  20. Cross-coupling reactions as valuable tool for the preparation of PET radiotracers.

    PubMed

    Pretze, Marc; Grosse-Gehling, Philipp; Mamat, Constantin

    2011-01-26

    The increasing application of positron emission tomography (PET) in nuclear medicine has stimulated the extensive development of a multitude of new radiotracers and novel radiolabeling procedures with the most prominent short-lived positron emitters carbon-11 and fluorine-18. Radiolabeling with these radionuclides represents a remarkable challenge. Special attention has to be paid to synthesis time and specific labeling techniques due to the short physical half life of the respective radionuclides ¹¹C (t(½) = 20.4 min) and ¹⁸F (t½) = 109.8 min). In the past, numerous transition metal-catalyzed reactions were employed in organic chemistry, even though only a handful of these coupling reactions were adopted in radiochemical practice. Thus, the implementation of modern synthesis methods like cross-coupling reactions offers the possibility to develop a wide variety of novel radiotracers. The introduction of catalysts based on transition metal complexes bears a high potential for rapid, efficient, highly selective and functional group-tolerating incorporation of carbon-11 and fluorine-18 into target molecules. This review deals with design, application and improvement of transition metal-mediated carbon-carbon as well as carbon-heteroatom cross-coupling reactions as a labeling feature with the focus on the preparation of radiolabeled compounds for molecular imaging.

  1. Protecting group-free, selective cross-coupling of alkyltrifluoroborates with borylated aryl bromides via photoredox/nickel dual catalysis.

    PubMed

    Yamashita, Yohei; Tellis, John C; Molander, Gary A

    2015-09-29

    Orthogonal reactivity modes offer substantial opportunities for rapid construction of complex small molecules. However, most strategies for imparting orthogonality to cross-coupling reactions rely on differential protection of reactive sites, greatly reducing both atom and step economies. Reported here is a strategy for orthogonal cross-coupling wherein a mechanistically distinct activation mode for transmetalation of sp(3)-hybridized organoboron reagents enables C-C bond formation in the presence of various protected and unprotected sp(2)-hybridized organoborons. This manifold has the potential for broad application, because orthogonality is inherent to the activation mode itself. The diversification potential of this platform is shown in the rapid elaboration of a trifunctional lynchpin through various transition metal-catalyzed processes without nonproductive deprotection or functional group manipulation steps.

  2. Protecting group-free, selective cross-coupling of alkyltrifluoroborates with borylated aryl bromides via photoredox/nickel dual catalysis

    PubMed Central

    Yamashita, Yohei; Tellis, John C.; Molander, Gary A.

    2015-01-01

    Orthogonal reactivity modes offer substantial opportunities for rapid construction of complex small molecules. However, most strategies for imparting orthogonality to cross-coupling reactions rely on differential protection of reactive sites, greatly reducing both atom and step economies. Reported here is a strategy for orthogonal cross-coupling wherein a mechanistically distinct activation mode for transmetalation of sp3-hybridized organoboron reagents enables C-C bond formation in the presence of various protected and unprotected sp2-hybridized organoborons. This manifold has the potential for broad application, because orthogonality is inherent to the activation mode itself. The diversification potential of this platform is shown in the rapid elaboration of a trifunctional lynchpin through various transition metal-catalyzed processes without nonproductive deprotection or functional group manipulation steps. PMID:26371299

  3. Native functionality in triple catalytic cross-coupling: sp³ C-H bonds as latent nucleophiles.

    PubMed

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

    2016-06-10

    The use of sp(3) C-H bonds--which are ubiquitous in organic molecules--as latent nucleophile equivalents for transition metal-catalyzed cross-coupling reactions has the potential to substantially streamline synthetic efforts in organic chemistry while bypassing substrate activation steps. Through the combination of photoredox-mediated hydrogen atom transfer (HAT) and nickel catalysis, we have developed a highly selective and general C-H arylation protocol that activates a wide array of C-H bonds as native functional handles for cross-coupling. This mild approach takes advantage of a tunable HAT catalyst that exhibits predictable reactivity patterns based on enthalpic and bond polarity considerations to selectively functionalize α-amino and α-oxy sp(3) C-H bonds in both cyclic and acyclic systems.

  4. Native functionality in triple catalytic cross-coupling: sp³ C-H bonds as latent nucleophiles.

    PubMed

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

    2016-06-10

    The use of sp(3) C-H bonds--which are ubiquitous in organic molecules--as latent nucleophile equivalents for transition metal-catalyzed cross-coupling reactions has the potential to substantially streamline synthetic efforts in organic chemistry while bypassing substrate activation steps. Through the combination of photoredox-mediated hydrogen atom transfer (HAT) and nickel catalysis, we have developed a highly selective and general C-H arylation protocol that activates a wide array of C-H bonds as native functional handles for cross-coupling. This mild approach takes advantage of a tunable HAT catalyst that exhibits predictable reactivity patterns based on enthalpic and bond polarity considerations to selectively functionalize α-amino and α-oxy sp(3) C-H bonds in both cyclic and acyclic systems. PMID:27127237

  5. Stereospecific Cross Couplings To Set Benzylic, All-Carbon Quaternary Stereocenters in High Enantiopurity.

    PubMed

    Zhou, Qi; Cobb, Kelsey M; Tan, Tianyu; Watson, Mary P

    2016-09-21

    Asymmetric preparation of all-carbon quaternary stereocenters is an important goal. Despite advances in formation of highly enantioenriched products with quaternary stereocenters proximal to a functional group, methods to install quaternary stereocenters isolated from functional groups are limited. Transition metal catalysis offers a potential solution, but prior cross couplings are limited to allylic substrates or deliver little to no enantiomeric enrichment. We report a stereospecific, nickel-catalyzed Suzuki-Miyaura arylation of tertiary benzylic acetates to deliver products with diaryl and triaryl quaternary stereocenters in high yields and ee's. This reaction employs an inexpensive, air-stable Ni(II) salt and commercially available phosphine ligand to transform tertiary alcohol derivatives, which are easily available in exceptional ee, into valuable products with stereoretention. PMID:27610831

  6. Asymmetric Suzuki Cross-Couplings of Activated Secondary Alkyl Electrophiles: Arylations of Racemic α-Chloroamides

    PubMed Central

    Lundin, Pamela M.; Fu, Gregory C.

    2010-01-01

    A nickel-catalyzed stereoconvergent method for the enantioselective Suzuki arylation of racemic α-chloroamides has been developed. This process represents the first example of an asymmetric arylation of an α-haloamide, of an enantioselective arylation of an α-chlorocarbonyl compound, and of an asymmetric Suzuki reaction with an activated alkyl electrophile or an arylboron reagent. The method is also applicable to the corresponding enantioselective cross-coupling of α-bromoamides. The coupling products can be transformed without racemization into useful enantioenriched α-arylcarboxylic acids and primary alcohols. An unprecedented (and modest) kinetic resolution of the α-chloroamide has been observed; a mechanistic study indicates that the selectivity likely reflects the discrimination by the chiral catalyst of the two enantiomeric α-chloroamides in an irreversible oxidative-addition process. PMID:20698665

  7. Decarbonylative organoboron cross-coupling of esters by nickel catalysis.

    PubMed

    Muto, Kei; Yamaguchi, Junichiro; Musaev, Djamaladdin G; Itami, Kenichiro

    2015-01-01

    The Suzuki-Miyaura cross-coupling is a metal-catalysed reaction in which boron-based nucleophiles and halide-based electrophiles are reacted to form a single molecule. This is one of the most reliable tools in synthetic chemistry, and is extensively used in the synthesis of pharmaceuticals, agrochemicals and organic materials. Herein, we report a significant advance in the choice of electrophilic coupling partner in this reaction. With a user-friendly and inexpensive nickel catalyst, a range of phenyl esters of aromatic, heteroaromatic and aliphatic carboxylic acids react with boronic acids in a decarbonylative manner. Overall, phenyl ester moieties function as leaving groups. Theoretical calculations uncovered key mechanistic features of this unusual decarbonylative coupling. Since extraordinary numbers of ester-containing molecules are available both commercially and synthetically, this new 'ester' cross-coupling should find significant use in synthetic chemistry as an alternative to the standard halide-based Suzuki-Miyaura coupling. PMID:26118733

  8. Decarbonylative organoboron cross-coupling of esters by nickel catalysis

    PubMed Central

    Muto, Kei; Yamaguchi, Junichiro; Musaev, Djamaladdin G.; Itami, Kenichiro

    2015-01-01

    The Suzuki–Miyaura cross-coupling is a metal-catalysed reaction in which boron-based nucleophiles and halide-based electrophiles are reacted to form a single molecule. This is one of the most reliable tools in synthetic chemistry, and is extensively used in the synthesis of pharmaceuticals, agrochemicals and organic materials. Herein, we report a significant advance in the choice of electrophilic coupling partner in this reaction. With a user-friendly and inexpensive nickel catalyst, a range of phenyl esters of aromatic, heteroaromatic and aliphatic carboxylic acids react with boronic acids in a decarbonylative manner. Overall, phenyl ester moieties function as leaving groups. Theoretical calculations uncovered key mechanistic features of this unusual decarbonylative coupling. Since extraordinary numbers of ester-containing molecules are available both commercially and synthetically, this new ‘ester' cross-coupling should find significant use in synthetic chemistry as an alternative to the standard halide-based Suzuki–Miyaura coupling. PMID:26118733

  9. Organoaluminum-mediated direct cross-coupling reactions.

    PubMed

    Minami, Hiroki; Saito, Tatsuo; Wang, Chao; Uchiyama, Masanobu

    2015-04-01

    We present a direct cross-coupling reaction between arylaluminum compounds (ArAlMe2 ⋅LiCl) and organic halides RX (R=aryl, alkenyl, alkynyl; X=I, Br, and Cl) without any external catalyst. The reaction takes place smoothly, simply upon heating, thereby enabling the efficient and chemo-/stereoselective formation of biaryl, alkene, and alkyne coupling products with broad functional group compatibility.

  10. The role of flavon cross couplings in leptonic flavour mixing

    NASA Astrophysics Data System (ADS)

    Pascoli, Silvia; Zhou, Ye-Ling

    2016-06-01

    In models with discrete flavour symmetries, flavons are critical to realise specific flavour structures. Leptonic flavour mixing originates from the misalignment of flavon vacuum expectation values which respect different residual symmetries in the charged lepton and neutrino sectors. Flavon cross couplings are usually forbidden, in order to protect these symmetries. Contrary to this approach, we show that cross couplings can play a key role and give raise to necessary corrections to flavour-mixing patterns, including a non-zero value for the reactor angle and CP violation. For definiteness, we present two models based on A 4. In the first model, all flavons are assumed to be real or pseudo-real, with 7 real degrees of freedom in the flavon sector in total. A sizable reactor angle associated with nearly maximal CP violation is achieved, and, as both originate from the same cross coupling, a sum rule results with a precise prediction for the value of the Dirac CP-violating phase. In the second model, the flavons are taken to be complex scalars, which can be connected with supersymmetric models and multi-Higgs models. The complexity properties of flavons provide new sources for generating the reactor angle. Models in this new approach introduce very few degrees of freedom beyond the Standard Model and can be more economical than those in the framework of extra dimension or supersymmetry.

  11. Cross-Couplings Using Aryl Ethers via C-O Bond Activation Enabled by Nickel Catalysts.

    PubMed

    Tobisu, Mamoru; Chatani, Naoto

    2015-06-16

    Arene synthesis has been revolutionized by the invention of catalytic cross-coupling reactions, wherein aryl halides can be coupled with organometallic and organic nucleophiles. Although the replacement of aryl halides with phenol derivatives would lead to more economical and ecological methods, success has been primarily limited to activated phenol derivatives such as triflates. Aryl ethers arguably represent one of the most ideal substrates in terms of availability, cost, safety, and atom efficiency. However, the robust nature of the C(aryl)-O bonds of aryl ethers renders it extremely difficult to use them in catalytic reactions among the phenol derivatives. In 1979, Wenkert reported a seminal work on the nickel-catalyzed cross-coupling of aryl ethers with Grignard reagents. However, it was not until 2004 that the unique ability of a low-valent nickel species to activate otherwise unreactive C(aryl)-O bonds was appreciated with Dankwardt's identification of the Ni(0)/PCy3 system, which significantly expanded the efficiency of the Wenkert reaction. Application of the nickel catalyst to cross-couplings with other nucleophiles was first accomplished in 2008 by our group using organoboron reagents. Later on, several other nucleophiles, including organozinc reagents, amines, hydrosilane, and hydrogen were shown to be coupled with aryl ethers under nickel catalysis. Despite these advances, progress in this field is relatively slow because of the low reactivity of benzene derivatives (e.g., anisole) compared with polyaromatic substrates (e.g., methoxynaphthalene), particularly when less reactive and synthetically useful nucleophiles are used. The "naphthalene problem" has been overcome by the use of N-heterocyclic carbene (NHC) ligands bearing bulky N-alkyl substituents, which enables a wide range of aryl ethers to be coupled with organoboron nucleophiles. Moreover, the use of N-alkyl-substituted NHC ligands allows the use of alkynylmagnesium reagents, thereby realizing

  12. Preparation of 2-BF3-substituted 1,3-dienes and their Diels-Alder/cross-coupling reactions.

    PubMed

    De, Subhasis; Welker, Mark E

    2005-06-01

    [reaction: see text] 2-BF3-substituted 1,3-butadienes with potassium and tetrabutylammonium counterions have been prepared in gram quantities from chloroprene via a simple synthetic procedure. The potassium salt of this new main group element substituted diene has been characterized by 1H, 13C, 11B, and 19F NMR. Diels-Alder reactions of these dienes with ethyl acrylate and methyl vinyl ketone are reported, as well as subsequent Pd-catalyzed cross-coupling reactions of those Diels-Alder adducts. PMID:15932228

  13. Development of a General, Sequential, Ring Closing Metathesis/Intramolecular Cross-Coupling Reaction for the Synthesis of Polyunsaturated Macrolactones

    PubMed Central

    Denmark, Scott E.; Muhuhi, Joseck M.

    2010-01-01

    A general strategy for the construction of macrocyclic lactones containing conjugated Z,Z-1,3-diene subunits has been is described. The centerpiece of the strategy is a sequential ring-closing metathesis that forms an unsaturated siloxane ring followed by an intramolecular cross-coupling reaction with a pendant alkenyl iodide. A highly modular assembly of the various precursors allowed the preparation of unsaturated macrolactones containing 11-, 12-, 13- and 14-membered rings. Although the ring closing metathesis process proceeded uneventfully, the intramolecular cross-coupling required extensive optimization of palladium source, solvent, fluoride source and particularly fluoride hydration level. Under the optimal conditions (including syringe pump high dilution), the macrolactones were produced in 53-78% yield as single stereoisomers. A benzo fused 12-membered ring macrolactone containing an E,Z-1,3-diene unit was also prepared by the same general strategy. The E-2-styryl iodide was prepared by a novel Heck reaction of an aryl nonaflate with vinyltrimethylsilane followed by iododesilylation with ICl. PMID:20666473

  14. Palladium contamination in silicon

    NASA Astrophysics Data System (ADS)

    Polignano, M. L.; Mica, I.; Ceresoli, M.; Codegoni, D.; Somaini, F.; Bianchi, I.; Volonghi, D.

    2015-04-01

    In this work palladium is characterized as a silicon contaminant by recombination lifetime, DLTS, C-V and C-t measurements of palladium-implanted wafers. Palladium introduced by ion implantation is found to remain in the solid solution in silicon after rapid thermal treatments, and to be a very effective recombination center. For this reason recombination lifetime measurements are the most sensitive method to detect palladium in silicon. Two palladium-related levels were found by DLTS in p-type material. One of these levels corresponds to a level reported in the literature as the single donor level of substitutional palladium. For what concerns MOS capacitors, palladium is responsible for negative oxide charge and for degradation of the generation lifetime. In addition, palladium is confirmed to be a very fast diffuser, which segregates at the wafer surface even with low temperature treatments (250 °C). Microscopy inspections showed that palladium precipitates and surface defects were formed upon segregation.

  15. Single-Electron Transmetalation: An Enabling Technology for Secondary Alkylboron Cross-Coupling

    PubMed Central

    Primer, David N.; Karakaya, Idris; Tellis, John C.; Molander, Gary A.

    2015-01-01

    Single-electron-mediated alkyl transfer affords a novel mechanism for transmetalation, enabling cross-coupling under mild conditions. Here, general conditions are reported for cross-coupling of secondary alkyltrifluoroborates with an array of aryl bromides mediated by an Ir photoredox catalyst and a Ni cross-coupling catalyst. PMID:25650892

  16. Asymmetric synthesis from terminal alkenes by diboration/cross-coupling cascades

    PubMed Central

    Mlynarski, Scott N.; Schuster, Christopher H.; Morken, James P.

    2013-01-01

    Amongst prospective starting materials for organic synthesis, terminal (monosubstituted) alkenes are ideal. In the form of α-olefins, they are manufactured on enormous scale and they are the core product features from many organic chemical reactions. While their latent reactivity can easily enable hydrocarbon chain extension, alkenes also have the attractive feature of being stable in the presence of many acids, bases, oxidants and reductants. In spite of these impressive attributes, relatively few catalytic enantioselective transformations have been developed that transform aliphatic α-olefins in >90% ee and, with the exception of site-controlled isotactic polymerization of α-olefins,1 none of these processes result in chain-extending C-C bond formation to the terminal carbon.2, 3, 4, 5, 6 Herein, we describe a strategy that directly addresses this gap in synthetic methodology and present a single-flask catalytic enantioselective conversion of terminal alkenes into a range of chiral products. These reactions are enabled by an unusual neighboring group participation effect that accelerates Pd-catalyzed cross-coupling of 1,2-bis(boronates) relative to nonfunctionalized alkyl boronate analogs. In tandem with enantioselective diboration, this reactivity feature connects abundant alkene starting materials to a diverse array of chiral products. Importantly with respect to synthesis utility, the tandem diboration/cross-coupling reaction (DCC reaction) generally provides products in high yield and high selectivity (>95:5 enantiomer ratio), employs low loadings (1–2 mol %) of commercially available catalysts and reagents, it offers an expansive substrate scope, and can address a broad range of alcohol and amine synthesis targets, many of which cannot be easily addressed with current technology. PMID:24352229

  17. INDIUM CHLORIDE CATALYZED CROSS-COUPLING OF DIHYDROPYRAN AND DIHYDROFURANS WITH ANILINES IN WATER. (R828129)

    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...

  18. Practical Ni-Catalyzed Aryl–Alkyl Cross-Coupling of Secondary Redox-Active Esters

    PubMed Central

    2016-01-01

    A new transformation is presented that enables chemists to couple simple alkyl carboxylic acids with aryl zinc reagents under Ni-catalysis. The success of this reaction hinges on the unique use of redox-active esters that allow one to employ such derivatives as alkyl halides surrogates. The chemistry exhibits broad substrate scope and features a high degree of practicality. The simple procedure and extremely inexpensive nature of both the substrates and pre-catalyst (NiCl2·6H2O, ca. $9.5/mol) bode well for the immediate widespread adoption of this method. PMID:26835704

  19. CuO hollow nanosphere-catalyzed cross-coupling of aryl iodides with thiols

    NASA Astrophysics Data System (ADS)

    Woo, Hyunje; Mohan, Balaji; Heo, Eunjung; Park, Ji Chan; Song, Hyunjoon; Park, Kang Hyun

    2013-09-01

    New functionalized CuO hollow nanospheres on acetylene black (CuO/AB) and on charcoal (CuO/C) have been found to be effective catalysts for C-S bond formation under microwave irradiation. CuO catalysts showed high catalytic activity with a wide variety of substituents which include electron-rich and electron-poor aryl iodides with thiophenols by the addition of two equivalents of K2CO3 as base in the absence of ligands.

  20. Cross-coupled control for all-terrain rovers.

    PubMed

    Reina, Giulio

    2013-01-01

    Mobile robots are increasingly being used in challenging outdoor environments for applications that include construction, mining, agriculture, military and planetary exploration. In order to accomplish the planned task, it is critical that the motion control system ensure accuracy and robustness. The achievement of high performance on rough terrain is tightly connected with the minimization of vehicle-terrain dynamics effects such as slipping and skidding. This paper presents a cross-coupled controller for a 4-wheel-drive/4-wheel-steer robot, which optimizes the wheel motors' control algorithm to reduce synchronization errors that would otherwise result in wheel slip with conventional controllers. Experimental results, obtained with an all-terrain rover operating on agricultural terrain, are presented to validate the system. It is shown that the proposed approach is effective in reducing slippage and vehicle posture errors. PMID:23299625

  1. Cross-coupled control for all-terrain rovers.

    PubMed

    Reina, Giulio

    2013-01-08

    Mobile robots are increasingly being used in challenging outdoor environments for applications that include construction, mining, agriculture, military and planetary exploration. In order to accomplish the planned task, it is critical that the motion control system ensure accuracy and robustness. The achievement of high performance on rough terrain is tightly connected with the minimization of vehicle-terrain dynamics effects such as slipping and skidding. This paper presents a cross-coupled controller for a 4-wheel-drive/4-wheel-steer robot, which optimizes the wheel motors' control algorithm to reduce synchronization errors that would otherwise result in wheel slip with conventional controllers. Experimental results, obtained with an all-terrain rover operating on agricultural terrain, are presented to validate the system. It is shown that the proposed approach is effective in reducing slippage and vehicle posture errors.

  2. Cross-Coupled Control for All-Terrain Rovers

    PubMed Central

    Reina, Giulio

    2013-01-01

    Mobile robots are increasingly being used in challenging outdoor environments for applications that include construction, mining, agriculture, military and planetary exploration. In order to accomplish the planned task, it is critical that the motion control system ensure accuracy and robustness. The achievement of high performance on rough terrain is tightly connected with the minimization of vehicle-terrain dynamics effects such as slipping and skidding. This paper presents a cross-coupled controller for a 4-wheel-drive/4-wheel-steer robot, which optimizes the wheel motors' control algorithm to reduce synchronization errors that would otherwise result in wheel slip with conventional controllers. Experimental results, obtained with an all-terrain rover operating on agricultural terrain, are presented to validate the system. It is shown that the proposed approach is effective in reducing slippage and vehicle posture errors. PMID:23299625

  3. Sample Characterization of Palladium Supported on Tetraphenylborate

    SciTech Connect

    Barnes, M.J.

    2001-04-04

    The primary objective of this research was to use XAFS spectroscopic techniques such as SANES and EXAFS to obtain information on Pd and Hg in samples that were potentially supported on KTPB and had been reacted with dissolved TPB and TPB decomposition products. This work was performed in support of the Small Tank Tetraphenylborate Salt Disposition Alternative program seeking to better understand the mechanism of palladium catalyzed tetraphenylborate decomposition.

  4. Highly selective and sensitive fluorescence chemosensor for the detection of palladium species based on Tsuji-Trost reaction.

    PubMed

    Xu, Zhong-Yong; Li, Jing; Guan, Su; Zhang, Lei; Dong, Chang-Zhi

    2015-09-01

    A new chemosensor 7-nitro-2,1,3-benzoxadiazole-4-allyl-N-(thiophen-2-ylmethyl)carbamate (NBDTC) was synthesized and utilized for palladium detection based on the Tsuji-Trost reaction. NBDTC displayed specific and ratiometric fluorescent responses toward palladium species. The chemosensor showed more than 50-fold enhancement in fluorescence intensity with the presence of PEG400 and palladium because NBDTC can be transformed to NBDT under palladium-catalyzing Tsuji-Trost reaction. NBDTC displayed high selectivity and sensitivity for palladium species with the detection limit of 1.13×10(-9) M.

  5. Organosulfur compounds: electrophilic reagents in transition-metal-catalyzed carbon-carbon bond-forming reactions.

    PubMed

    Dubbaka, Srinivas Reddy; Vogel, Pierre

    2005-12-01

    Transition-metal-catalyzed carbon-carbon bond-forming reactions are among the most powerful methods in organic synthesis and play a crucial role in modern materials science and medicinal chemistry. Recent developments in the area of ligands and additives permit the cross-coupling of a large variety of reactants, including inexpensive and readily available sulfonyl chlorides. Their desulfitative carbon-carbon cross-coupling reactions (Negishi, Stille, carbonylative Stille, Suzuki-Miyaura, and Sonogashira-Hagihara-type cross-couplings and Mizoroki-Heck-type arylations) are reviewed together with carbon-carbon cross-coupling reactions with other organosulfur compounds as electrophilic reagents.

  6. Photoredox Cross-Coupling: Ir/Ni Dual Catalysis for the Synthesis of Benzylic Ethers

    PubMed Central

    2015-01-01

    Single-electron transmetalation has emerged as an enabling paradigm for the cross-coupling of Csp3 hybridized organotrifluoroborates. Cross-coupling of α-alkoxymethyltrifluoroborates with aryl and heteroaryl bromides has been demonstrated by employing dual catalysis with a combination of an iridium photoredox catalyst and a Ni cross-coupling catalyst. The resulting method enables the alkoxymethylation of diverse (hetero)arenes under mild, room-temperature conditions. PMID:26079182

  7. Synthesis of Indeno[1',2':4,5]imidazo[1,2-a]pyridin-11-ones and Chromeno[4',3':4,5]imidazo[1,2-a]pyridin-6-ones through Palladium-Catalyzed Cascade Reactions of 2-(2-Bromophenyl)imidazo[1,2-a]pyridines.

    PubMed

    Zhang, Ju; Zhang, Xinying; Fan, Xuesen

    2016-04-15

    A novel and efficient synthesis of 11H-indeno[1',2':4,5]imidazo[1,2-a]pyridin-11-one, a hybrid structure of indenone with imidazo[1,2-a]pyridine, from the reaction of 2-(2-bromophenyl)imidazo[1,2-a]pyridine with carbon monoxide through palladium-catalyzed CO insertion and C-H bond activation, has been developed. Intriguingly, under similar conditions but in the presence of Cu(OAc)2, the reaction selectively afforded 6H-chromeno[4',3':4,5]imidazo[1,2-a]pyridin-6-one, a hybrid structure of chromenone with imidazo[1,2-a]pyridine, via a more sophisticated cascade process including acetoxylation, deacetylation, CO insertion, and C-H bond activation. PMID:26980482

  8. Metallaphotoredox-catalysed sp3–sp3 cross-coupling of carboxylic acids with alkyl halides

    NASA Astrophysics Data System (ADS)

    Johnston, Craig P.; Smith, Russell T.; Allmendinger, Simon; MacMillan, David W. C.

    2016-08-01

    In the past 50 years, cross-coupling reactions mediated by transition metals have changed the way in which complex organic molecules are synthesized. The predictable and chemoselective nature of these transformations has led to their widespread adoption across many areas of chemical research. However, the construction of a bond between two sp3-hybridized carbon atoms, a fundamental unit of organic chemistry, remains an important yet elusive objective for engineering cross-coupling reactions. In comparison to related procedures with sp2-hybridized species, the development of methods for sp3–sp3 bond formation via transition metal catalysis has been hampered historically by deleterious side-reactions, such as β-hydride elimination with palladium catalysis or the reluctance of alkyl halides to undergo oxidative addition. To address this issue, nickel-catalysed cross-coupling processes can be used to form sp3–sp3 bonds that utilize organometallic nucleophiles and alkyl electrophiles. In particular, the coupling of alkyl halides with pre-generated organozinc, Grignard and organoborane species has been used to furnish diverse molecular structures. However, the manipulations required to produce these activated structures is inefficient, leading to poor step- and atom-economies. Moreover, the operational difficulties associated with making and using these reactive coupling partners, and preserving them through a synthetic sequence, has hindered their widespread adoption. A generically useful sp3–sp3 coupling technology that uses bench-stable, native organic functional groups, without the need for pre-functionalization or substrate derivatization, would therefore be valuable. Here we demonstrate that the synergistic merger of photoredox and nickel catalysis enables the direct formation of sp3–sp3 bonds using only simple carboxylic acids and alkyl halides as the nucleophilic and electrophilic coupling partners, respectively. This metallaphotoredox protocol is

  9. Ruthenium-catalyzed cycloadditions of 1-haloalkynes with nitrile oxides and organic azides: synthesis of 4-haloisoxazoles and 5-halotriazoles.

    PubMed

    Oakdale, James S; Sit, Rakesh K; Fokin, Valery V

    2014-08-25

    (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 equivalents 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 by using palladium-catalyzed cross-coupling reactions and by manipulation of reactive amide groups. The lack of catalysis observed with [Cp*RuCl(cod)] (Cp* = pentamethylcyclopentadienyl) is attributed to steric demands of the Cp* (η(5)-C5Me5) ligand in comparison to the parent Cp (η(5)-C5H5). This hypothesis is supported by the poor reactivity of [(η(5)-C5Me4CF3)RuCl(cod)], which serves as a an isosteric mimic of Cp* and as an isoelectronic analogue of Cp. PMID:25059647

  10. Surface-plasmon cross coupling in molecular fluorescence near a corrugated thin metal film

    NASA Technical Reports Server (NTRS)

    Gruhlke, R. W.; Holland, W. R.; Hall, D. G.

    1968-01-01

    Surface plasmons on opposite sides of a thin metal film can cross couple in the presence of a surface corrugation, or grating. The observation of this cross-coupling phenomenon as a radiative-decay mechanism for molecules near a corrugated thin metal film is reported.

  11. Gold/Palladium Alloy for Carbon-Halogen Bond Activation: An Unprecedented Halide Dependence.

    PubMed

    Dhital, Raghu Nath; Bobuatong, Karan; Ehara, Masahiro; Sakurai, Hidehiro

    2015-12-01

    New catalytic activity of gold/palladium alloy nanoclusters (NCs) for carbon-halogen bond activation is demonstrated. In the case of an aryl chloride, the inclusion of gold in a bimetallic catalyst is indispensable to achieve the coupling reactions. Gold has the unique effect of stabilizing palladium, such that Pd(2+) leached from clusters by means of spillover of chloride during oxidative addition. The thus-formed spillover intermediate further reacts heterogeneously in both Ullmann and Suzuki-type coupling reactions through a new type of mechanism. In the case of an aryl bromide, Ullmann coupling occurs through the spillover of bromide, similar to that of aryl chloride. However, a significant fraction of palladium also leached, which diminished the Ullmann coupling activity of the aryl bromide and, as a result, the order of reactivity was ArCl>ArBr. With regard to the activation of the C-Br bond towards a Suzuki-type reaction, the inclusion of a higher gold content in gold/palladium clusters stabilized palladium to prevent the leaching of Pd(2+) from the clusters by means of spillover of bromide. The spillover intermediate reacts heterogeneously with PhB(OH)2, palladium-rich gold/palladium, or pure palladium clusters; the oxidative addition of ArBr favors the extraction of palladium from the clusters, yielding Pd(2+) intermediates. The extracted intermediates react homogenously (Pd(2+/)Pd(0) catalysis) with PhB(OH)2, which results in the higher selectivity of the cross-coupling product. An initial step to observe such unprecedented halide dependency, together with the dynamic behavior of palladium on the surface of gold is the oxidative addition of Ar-X. A detailed insight into the first oxidative addition process was also examined by quantum chemical calculations.

  12. 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

  13. Oxidative β-Csp(3) -H Functionalization of tBuOH: A Selective Radical/Radical Cross-Coupling Access to β-Hydroxy Thioethers.

    PubMed

    Li, Yuxiu; Liu, Dong; Liu, Chao; Lei, Aiwen

    2016-08-19

    An oxidative β-Csp(3) -H functionalization of tert-butanol (tBuOH) for the construction of C-S bonds through an iodine-catalyzed Csp(3) -H/S-H coupling was successfully achieved. Different kinds of mercaptans were shown to be good coupling partners, affording the desired products in good yields. This protocol not only offers a novel method for the synthesis of β-hydroxy thioethers, but also provides an effective strategy for selective radical/radical cross-coupling. PMID:27378452

  14. 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

  15. One pot synthesis of diarylfurans from aryl esters and PhI(OAc)2 via palladium-associated iodonium ylides.

    PubMed

    Bao, Yong-Sheng; Agula, Bao; Zhaorigetu, Bao; Jia, Meilin; Baiyin, Menghe

    2015-04-14

    The example of palladium-catalyzed intermolecular cyclization for the synthesis of various diarylfurans in which one of the aromatic rings originates from the phenolic part of the starting ester and the other one from PhI(OAc)2 has been reported. The reaction is carried out through two steps: the rearrangement of palladium-associated iodonium ylides to form o-iodo diaryl ether and then palladium catalyzed intramolecular direct arylation. This reaction can tolerate a variety of functional groups and is alternative or complementary to the previous methods for the synthesis of diarylfurans.

  16. Total Synthesis of Enantiopure (+)-γ -Lycorane Using Highly Efficient Pd-Catalyzed Asymmetric Allylic Alkylation

    PubMed Central

    Chapsal, Bruno D.; Ojima, Iwao

    2008-01-01

    Highly efficient short total synthesis of γ -lycorane (>99% ee, 41% overall yield) was achieved by using the asymmetric allylic alkylation in the key step catalyzed by palladium complexes with novel chiral biphenol-based monodentate phosphoramidite ligands. PMID:16562900

  17. A novel ratiometric sensor for the fast detection of palladium species with large red-shift and high resolution both in aqueous solution and solid state.

    PubMed

    Cui, Lei; Zhu, Weiping; Xu, Yufang; Qian, Xuhong

    2013-07-01

    A highly selective fluorescent probe (OHBT) was designed and synthesized by linking the ESIPT fluorophore N-(3-(benzo[d]thiazol-2-yl)-4-(hydroxyphenyl) benzamide) (HBTBC) to the palladium specificity response group, allyl group, for the detection of palladium species in aqueous solution. The allyl group can be hydrolyzed by Pd(0) species through the Pd(0)-catalyzed Tsuji-Trost reaction and thus release the fluorophore HBTBC, which shows two emission bands. The maximum emission spectra originated from the enol and keto forms at 415 and 555 nm respectively and with no overlap, which implies the high resolution of the palladium detection. The palladium species can also be detected by paper strip because of the solid-state fluorescence of probe HOBT catalyzed by palladium. This method was successfully applied in the palladium related Suzuki-Miyaura coupling reaction and the detection limit is lower than 1 μM.

  18. A palladium-nanoparticle and silicon-nanowire-array hybrid: a platform for catalytic heterogeneous reactions.

    PubMed

    Yamada, Yoichi M A; Yuyama, Yoshinari; Sato, Takuma; Fujikawa, Shigenori; Uozumi, Yasuhiro

    2014-01-01

    We report the development of a silicon nanowire array-stabilized palladium nanoparticle catalyst, SiNA-Pd. Its use in the palladium-catalyzed Mizoroki-Heck reaction, the hydrogenation of an alkene, the hydrogenolysis of nitrobenzene, the hydrosilylation of an α,β-unsaturated ketone, and the C-H bond functionalization reactions of thiophenes and indoles achieved a quantitative production with high reusability. The catalytic activity reached several hundred-mol ppb of palladium, reaching a TON of 2 000 000.

  19. Pd-NHC-Catalyzed Alkynylation of General Aryl Sulfides with Alkynyl Grignard Reagents.

    PubMed

    Baralle, Alexandre; Yorimitsu, Hideki; Osuka, Atsuhiro

    2016-07-25

    Cross-coupling reactions of unactivated aryl sulfides with alkynylmagnesium chloride have been invented to afford 1-aryl-1-alkynes with the aid of a palladium/N-heterocyclic carbene complex. This reaction has by far the widest scope of all transformations utilizing aryl sulfides and alkynes, while known cross-coupling alkynylations of aryl-sulfur electrophiles require activated azaaryl sulfides, thiolactams, or arenesulfonyl chlorides. The alkynylation of aryl sulfides is compatible with typical protecting functional groups. The alkynylation is applied to the synthesis of benzofuran-based fluorescent molecules by taking advantage of characteristic organosulfur chemistry.

  20. Pd-NHC-Catalyzed Alkynylation of General Aryl Sulfides with Alkynyl Grignard Reagents.

    PubMed

    Baralle, Alexandre; Yorimitsu, Hideki; Osuka, Atsuhiro

    2016-07-25

    Cross-coupling reactions of unactivated aryl sulfides with alkynylmagnesium chloride have been invented to afford 1-aryl-1-alkynes with the aid of a palladium/N-heterocyclic carbene complex. This reaction has by far the widest scope of all transformations utilizing aryl sulfides and alkynes, while known cross-coupling alkynylations of aryl-sulfur electrophiles require activated azaaryl sulfides, thiolactams, or arenesulfonyl chlorides. The alkynylation of aryl sulfides is compatible with typical protecting functional groups. The alkynylation is applied to the synthesis of benzofuran-based fluorescent molecules by taking advantage of characteristic organosulfur chemistry. PMID:27223101