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Sample records for palladium catalyzed cross-coupling

  1. Palladium-catalyzed cross-coupling reactions of silanolates: a paradigm shift in silicon-based cross-coupling reactions.

    PubMed

    Denmark, Scott E; Baird, John D

    2006-06-23

    This paper chronicles the conceptual development, proof of principle experiments, and recent advances in the palladium-catalyzed cross-coupling reactions of the conjugate bases of organosilanols. The discovery that led to the design and refinement of this process represents a classical illustration of how mechanistic studies can provide a fertile ground for the invention of new reactions. On the basis of a working hypothesis (which ultimately proved to be incorrect) and the desire to effect silicon-based cross-coupling without the agency of fluoride activation, a mild and practical palladium-catalyzed cross-coupling of alkenyl-, aryl-, and heteroaryl silanolates has been developed. The mechanistic underpinnings, methodological extensions, and the successful applications of this technology to the synthesis of complex molecules are described.

  2. Palladium-catalyzed cross-coupling of benzyl chlorides with cyclopropanol-derived ketone homoenolates.

    PubMed

    Nithiy, Nisha; Orellana, Arturo

    2014-11-21

    The palladium-catalyzed cross-coupling reaction of cyclopropanol-derived ketone homoenolates with benzyl chlorides is reported. This reaction proceeds in high yields with electron-neutral and electron-rich benzyl chlorides; however, yields are low with electron-poor benzyl chlorides. In addition, a range of cyclopropanols can be coupled in good yields. The reaction can be conducted with a low catalyst loading (1% Pd) and on a gram scale without reduction in yield.

  3. Palladium-catalyzed cross-coupling of aryl fluorides with N-tosylhydrazones via C-F bond activation.

    PubMed

    Luo, Haiqing; Wu, Guojiao; Xu, Shuai; Wang, Kang; Wu, Chaoqiang; Zhang, Yan; Wang, Jianbo

    2015-09-04

    A palladium-catalyzed cross-coupling reaction of electron-deficient aryl fluorides with aryl N-tosylhydrazones has been reported. Mechanistically, this approach involves C-F bond activation and migratory insertion of palladium carbene as the two key steps.

  4. Palladium-catalyzed cross-coupling reactions of aryl boronic acids with aryl halides in water.

    PubMed

    Wang, Shaoyan; Zhang, Zhiqiang; Hu, Zhizhi; Wang, Yue; Lei, Peng; Chi, Haijun

    2009-01-01

    An efficient Suzuki cross-coupling reaction using a variety of aryl halides in neat water was developed. The Pd-catalyzed reaction between aryl bromides or chlorides and phenyl boronic acids was compatible with various functional groups and affords biphenyls in good to excellent yields without requirement of organic cosolvents. The air stability and solubility in water of the palladium-phosphinous acid complexes were considered to facilitate operation of the coupling reaction and product isolation. The reaction conditions including Pd catalyst selection, temperature, base and catalyst recoverability were also investigated.

  5. Palladium-Catalyzed Cross-Coupling Reactions of Organosilanols and their Salts

    PubMed Central

    Denmark, Scott E.; Regens, Christopher S.

    2009-01-01

    Conspectus 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 that require no activation or the boron-based reactions that 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

  6. Palladium(0)-catalyzed suzuki-miyaura cross-coupling reactions of potassium aryl- and heteroaryltrifluoroborates with alkenyl bromides.

    PubMed

    Molander, Gary A; Fumagalli, Tiziano

    2006-07-21

    Efficient palladium(0)-catalyzed Suzuki-Miyaura cross-couplings are described. The reactions involving potassium aryl- and heteroaryltrifluoroborates with alkenyl bromides can generally be carried out using < or =2 mol % of palladium catalyst and 3 equiv of base in toluene/H2O. When stereodefined alkenyl bromides are employed, the resulting styrene derivatives are accessed stereospecifically. A variety of functional groups are tolerated in both coupling partners.

  7. 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.

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

    PubMed Central

    2015-01-01

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

  9. On the Stereochemical Course of Palladium-Catalyzed Cross-Coupling of Allylic Silanolate Salts with Aromatic Bromides

    PubMed Central

    Denmark, Scott E.; Werner, Nathan S.

    2010-01-01

    The stereochemical course of palladium-catalyzed cross-coupling reactions of an enantioenriched, α-substituted, allylic silanolate salt with aromatic bromides has been investigated. The allylic silanolate salt was prepared in high geometrical (Z/E, 94:6) and high enantiomeric (94:6 er) purity by a copper-catalyzed SN2’ reaction of a resolved allylic carbamate. Eight different aromatic bromides underwent cross-coupling with excellent constitutional site selectivity (γ) and with excellent stereospecificity. Stereochemical correlation established that the transmetalation event proceeds through a syn SE’ mechanism which is interpreted in terms of an intramolecular delivery of the arylpalladium electrophile through a key intermediate that contains a discrete Si–O–Pd linkage. PMID:20163185

  10. Triorganoindium reagents in selective palladium-catalyzed cross-coupling with iodoimidazoles: synthesis of neurodazine.

    PubMed

    Pérez-Caaveiro, Cristina; Pérez Sestelo, José; Martínez, M Montserrat; Sarandeses, Luis A

    2014-10-17

    Triorganoindium reagents (R3In, R = aryl, heteroaryl, alkynyl) react selectively under palladium catalysis with N-benzyl-2,4,5-triiodoimidazole to afford the C-2 monocoupling products. The reaction proceeds efficiently for a variety of aryl- and heteroarylindium reagents with the transfer of all three organic groups attached to the metal. The coupling products can be used in a subsequent two-fold cross-coupling to give trisubstituted imidazoles in good yields. This approach was employed to synthesize neurodazine and analogues in good yields.

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

    PubMed Central

    2016-01-01

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

  12. Palladium-Catalyzed Ullmann Cross-Coupling/Tandem Reductive Cyclization Route to Key Members of the Uleine Alkaloid Family.

    PubMed

    Tang, Fei; Banwell, Martin G; Willis, Anthony C

    2016-04-01

    The trisubstituted cyclohexenone 12, generated through a palladium-catalyzed Ullmann cross-coupling reaction between o-iodonitrobenzene and a 4,5-trans-disubstituted 2-iodo-2-cyclohexen-1-one, engaged in a tandem reductive cyclization process upon exposure to hydrogen gas in the presence of Raney cobalt. As a result, the 1,5-methanoazocino[4,3-b]indole 13 was obtained and this could be readily elaborated to the racemic modifications of the alkaloids uleine, dasycarpidone, noruleine, and nordasycarpidone (1-4, respectively).

  13. Highly Selective Palladium-Catalyzed Cross-Coupling of Secondary Alkylzinc Reagents with Heteroaryl Halides

    PubMed Central

    2015-01-01

    The highly selective palladium-catalyzed Negishi coupling of secondary alkylzinc reagents with heteroaryl halides is described. The development of a series of biarylphosphine ligands has led to the identification of an improved catalyst for the coupling of electron-deficient heterocyclic substrates. Preparation and characterization of oxidative addition complex (L)(Ar)PdBr provided insight into the unique reactivity of catalysts based on CPhos-type ligands in facilitating challenging reductive elimination processes. PMID:25153332

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

    PubMed

    McMahon, Caitlin M; Alexanian, Erik J

    2014-06-02

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

  15. Palladium-catalyzed substitution and cross-coupling of benzylic fluorides.

    PubMed

    Blessley, George; Holden, Patrick; Walker, Matthew; Brown, John M; Gouverneur, Véronique

    2012-06-01

    Benzylic fluorides are suitable substrates for Pd(0)-catalyzed Tsuji-Trost substitution using carbon, nitrogen, oxygen, and sulfur nucleophiles and for cross-coupling with phenylboronic acid. For the bifunctional substrate 4-chlorobenzyl fluoride, fine-tuning of the reaction conditions allows for the regioselective displacement of either the chlorine or fluorine substituent. The leaving group ability of fluoride vs other groups displaced in substitution is CF(3)CO(2) ≈ p-NO(2)C(6)H(4)CO(2) ≈ OCO(2)CH(3) > F > CH(3)CO(2), a ranking similar to allylic fluorides under Pd catalysis.

  16. 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.

  17. Functionalized heteroarylpyridazines and pyridazin-3(2H)-one derivatives via palladium-catalyzed cross-coupling methodology.

    PubMed

    Clapham, Kate M; Batsanov, Andrei S; Greenwood, Ryan D R; Bryce, Martin R; Smith, Amy E; Tarbit, Brian

    2008-03-21

    A general method for the synthesis of functionalized pyridazinylboronic acids/esters is described involving a directed ortho metalation (DoM)--boronation protocol (Schemes 1 and 2). A comprehensive study of the reactivity of the C-B bond in palladium-catalyzed cross-couplings with aryl/heteroaryl halides is presented. Aryl-/heteroarylpyridazines are thereby obtained in synthetically viable yields (typically 40-75%) although in some cases competing protodeboronation has been observed. A series of pyridazin-3(2H)-one derivatives, including 4,6-diaryl/heteroaryl derivatives, have been obtained from the corresponding 3-methoxypyridazines in straightforward procedures (Schemes 3 and 4). Several X-ray crystal structures of aryl-/heteroarylpyridazines and derived pyridazin-3(2H)-one derivatives are reported. These multi-ring systems are of considerable interest in contemporary N-heterocyclic chemistry.

  18. 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.

  19. 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].

  20. Branched/linear selectivity in palladium-catalyzed allyl-allyl cross-couplings: The role of ligands.

    PubMed

    Ardolino, Michael J; Morken, James P

    2015-09-16

    While Pd-catalyzed allyl-allyl cross-couplings in the presence of small-bite-angle bidentate ligands reliably furnish the branched regioisomer with high levels of selectivity, cross-couplings in the presence of large-bite-angle bidentate ligands give varying, often unpredictable, levels of selectivity. In a combined computational and experimental study, we probe the underlying features that govern the regioselectivity in these metal-catalyzed cross-couplings.

  1. Sequential Processes in Palladium-Catalyzed Silicon-Based Cross-Coupling

    PubMed Central

    Denmark, Scott E.; Liu, Jack H.-C.

    2012-01-01

    Although developed somewhat later, silicon-based cross-coupling has become a viable alternative to the more conventional Suzuki-Miyaura, Stille-Kosugi-Migita, and Negishi cross-coupling reactions because of its broad substrate scope, high stability of silicon-containing reagents, and low toxicity of waste streams. An empowering and yet underappreciated feature unique to silicon-based cross-coupling is the wide range of sequential processes available. In these processes, simple precursors are first converted to complex silicon-containing cross-coupling substrates, and the subsequent silicon-based cross-coupling reaction affords an even more highly functionalized product in a stereoselective fashion. In so doing, structurally simple and inexpensive starting materials are quickly transformed into value-added and densely substituted products. Therefore, sequential processes are often useful in constructing the carbon backbones of natural products. In this review, studies of sequential processes involving silicon-based cross-coupling are discussed. Additionally, the total syntheses that utilize these sequential processes are also presented. PMID:23293392

  2. Palladium-catalyzed cross-coupling of cyclopropylmagnesium bromide with aryl bromides mediated by zinc halide additives.

    PubMed

    Shu, Chutian; Sidhu, Kanwar; Zhang, Li; Wang, Xiao-Jun; Krishnamurthy, Dhileepkumar; Senanayake, Chris H

    2010-10-01

    The key Pd-catalyzed cross-coupling of aryl bromides or triflates and cyclopropylmagnesium bromide in the presence of substoichiometric amounts of zinc bromide produces cyclopropyl arenes in good to excellent yields. The cross-coupling of other alkyl, cycloalkyl, and aryl Grignard reagents with aryl bromides under the same conditions gives the corresponding substituted arenes in good yields.

  3. Palladium catalyzed one-pot sequential Suzuki cross-coupling-direct C-H functionalization of imidazo[1,2-a]pyrazines.

    PubMed

    Gembus, Vincent; Bonfanti, Jean-François; Querolle, Olivier; Jubault, Philippe; Levacher, Vincent; Hoarau, Christophe

    2012-12-07

    An efficient "one-pot" selective functionalization at C3/C6 of imidazo[1,2-a]pyrazines has been developed via a palladium-catalyzed sequential Suzuki-Miyaura cross-coupling/direct C-H arylation, vinylation, and benzylation. The procedure remains effective in the presence of a methyl thioether group at C8, which may in turn be successfully engaged in a cross-coupling method to afford 3,6,8-trisubstituted imidazo[1,2-a]pyrazines. This work paves the way for the design of biologically relevant compounds in an imidazo[1,2-a]pyrazine series.

  4. Palladium-catalyzed cross coupling reaction of N-alkoxyimidoyl bromides and its application to one-pot synthesis of N-arylamines.

    PubMed

    Ueda, Masafumi; Sugita, Shoichi; Aoi, Naoki; Sato, Aoi; Ikeda, Yuki; Ito, Yuta; Miyoshi, Tetsuya; Naito, Takeaki; Miyata, Okiko

    2011-01-01

    The synthetic utility of N-alkoxyimidoyl halides is demonstrated using the palladium-catalyzed cross-coupling reaction. The Sonogashira and Suzuki-Miyaura coupling reactions of N-alkoxyimidoyl bromides produced versatile ketoxime ethers in good to excellent yields. A one-pot reaction of the imidoyl bromides with arylboronic acid and allylmagnesium bromide to produce N-arylamines via Suzuki-Miyaura coupling followed by domino reaction involving sequential addition-eliminative rearrangement-addition reactions was developed.

  5. 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.

  6. 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

  7. Palladium-catalyzed cross-coupling reactions of arylsiloxanes with aryl halides: application to solid-supported organic synthesis.

    PubMed

    Traficante, Carla I; Delpiccolo, Carina M L; Mata, Ernesto G

    2014-05-12

    The solid-phase version of the Pd-catalyzed Hiyama reaction between a variety of aryltriethoxysilanes and immobilized aryl halides was developed. Smooth cross-coupling was achieved to afford the corresponding biaryl products in moderate to excellent yields. The described protocol would be particularly useful for the construction of 4'-substituted 1,1'-biphenyl derivatives.

  8. AlAr3(THF): highly efficient reagents for cross-couplings with aryl bromides and chlorides catalyzed by the economic palladium complex of PCy3.

    PubMed

    Ku, Shih-Lun; Hui, Xin-Ping; Chen, Chien-An; Kuo, Yi-Ying; Gau, Han-Mou

    2007-10-07

    Novel and highly efficient cross couplings of aryl bromides and chlorides with AlAr3(THF) (Ar = Ph, 2,4,6-Me3C6H2, 2-naphthyl or 4-Me3SiC6H4) catalyzed by the economic palladium catalyst of PCy3 are reported without the use of a base and under mild reaction conditions at room temperature or temperatures < or = 60 degrees C even for couplings of bulky aryl halides and the Al(2,4,6-Me3C6H2)3(THF) reagent.

  9. Cross-coupling of diarylborinic acids and anhydrides with arylhalides catalyzed by a phosphite/N-heterocyclic carbene co-supported palladium catalyst system.

    PubMed

    Chen, Xiaofeng; Ke, Haihua; Chen, Yao; Guan, Changwei; Zou, Gang

    2012-09-07

    A highly efficient cross-coupling of diarylborinic acids and anhydrides with aryl chlorides and bromides has been effected by using a palladium catalyst system co-supported by a strong σ-donor N-heterocyclic carbene (NHC), N,N'-bis(2,6-diisopropylphenyl) imidazol-2-ylidene, and a strong π-acceptor phosphite, triphenylphosphite, in tert-BuOH in the present of K(3)PO(4)·3H(2)O. Unsymmetrical biaryls with a variety of functional groups could be obtained in good to excellent yields using as low as 0.01, 0.2-0.5, and 1 mol % palladium loadings for aryl bromides and activated and deactivated aryl chlorides, respectively, under mild conditions. A ligand synergy between the σ-donor NHC and the π-acceptor phosphite in the Pd/NHC/P(OPh)(3) catalytic system has been proposed to be responsible for the high efficacy to arylchlorides in the cross-coupling. A scalable and economical process has therefore been developed for synthesis of Sartan biphenyl from the Pd/NHC/P(OPh)(3) catalyzed cross-coupling of di(4-methylphenyl)borinic acid with 2-chlorobenzonitrile.

  10. Palladium-catalyzed cross-coupling reactions of amines with alkenyl bromides: a new method for the synthesis of enamines and imines.

    PubMed

    Barluenga, José; Fernández, M Alejandro; Aznar, Fernando; Valdés, Carlos

    2004-01-23

    The palladium-catalyzed cross-coupling reaction of alkenyl bromides with secondary and primary amines gives rise to enamines and imines, respectively. This new transformation expands the applicability of palladium-catalyzed C-N bond forming reactions (the Buchwald-Hartwig amination), which have mostly been applied to aryl halides. After screening of different ligands, bases, and solvents, the catalytic combination [Pd(2)(dba)(3)]/BINAP in the presence of NaOtBu in toluene gave the best results in the cross-coupling of secondary amines with 1-bromostyrene (dba=dibenzylideneacetone, BINAP=2,2'-bis(diphenylphosphino)-1,1'-binaphthyl). The corresponding enamines are obtained cleanly and in nearly quantitative yields. However, steric hindrance seems to be a limitation of the reaction, as amines carrying large substituents are not well converted. The same methodology can be applied to the coupling of secondary amines with 2-bromostyrene. Moreover, the reaction with substituted 2-bromopropenes allows regioselective synthesis of isomerizable terminal enamines without isomerization of the double bond. The best catalytic conditions for the cross-coupling of 1-bromostyrene with primary amines include again the use of the Pd(0)/BINAP/NaOtBu system. The reaction gives rise to the expected imines in very short times and with low catalyst loadings. A set of structurally diverse imines can be prepared by this methodology through variations in the structure of both coupling partners. However, 2-bromostyrene failed to give good results in this coupling reaction, probably due to product inhibition of the catalytic cycle. Competition experiments of vinyl versus aryl amination reveal that the reaction occurs preferentially on vinyl bromides.

  11. 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

  12. Synthesis of a double helicene by a palladium-catalyzed cross-coupling reaction: structure and physical properties.

    PubMed

    Kashihara, Hitoshi; Asada, Toshio; Kamikawa, Ken

    2015-04-20

    For this study, twisted π-extended helicene 1 and double helicene 2 with a helicene framework were synthesized through palladium-catalyzed C-H arylation or Suzuki-Miyaura coupling reaction. X-ray crystallography revealed grossly twisted structures that were soluble in various conventional organic solvents. Optical properties based on UV/Vis and fluorescence spectra were measured. Electrochemical properties were also studied by measurements of cyclic voltammetry in 1 and 2, which revealed their HOMO and the LUMO energies. Theoretical calculation supports their HOMO and LUMO energies and molecular orbitals. Furthermore, a racemization process of 2 predicted that the activation free energy at 300 K would be 31.8 kcal mol(-1) by DFT calculation, which indicated the static helicity at 300 K.

  13. Theoretical Bond Dissociation Energies of Halo-Heterocycles: Trends and Relationships to Regioselectivity in Palladium-Catalyzed Cross-Coupling Reactions

    PubMed Central

    Garcia, Yeimy; Schoenebeck, Franziska; Legault, Claude Y.; Merlic, Craig A.; Houk, K. N.

    2009-01-01

    Selectivity of the palladium-catalyzed cross-coupling reactions of heterocycles bearing multiple identical halogens is mainly determined by the relative ease of oxidative addition. This is related to both the energy to distort the carbon halogen bond to the transition-state geometry (related to the CX bond-dissociation energy) and to the interaction between the heterocycle π* (LUMO) and PdL2 HOMO (J. Am. Chem. Soc. 2007, 129, 12664). The computed bond dissociation energies of a larger series of halo-heterocycles have been explored with B3LYP and higher accuracy G3B3 calculations. Quantitative trends in bond dissociation energies have been identified for five- and six-membered chloro and bromo substituted heterocycles with N, O, and S heteroatoms. PMID:19368385

  14. Synthesis of dienyl ketones via palladium(II)-catalyzed direct cross-coupling reactions between simple alkenes and vinyl ketones: application to the synthesis of vitamin A1 and bornelone.

    PubMed

    Zhang, Xiang; Wang, Min; Zhang, Ming-Xin; Xu, Yun-He; Loh, Teck-Peng

    2013-11-01

    An efficient and general method for the synthesis of conjugated dienyl ketones via palladium(II) acetate catalyzed direct cross-coupling between simple alkenes and vinyl ketones is reported. This method has been successfully applied for the synthesis of Vitamin A1 and bornelone.

  15. Pyridine sulfinates as general nucleophilic coupling partners in palladium-catalyzed cross-coupling reactions with aryl halides.

    PubMed

    Markovic, Tim; Rocke, Benjamin N; Blakemore, David C; Mascitti, Vincent; Willis, Michael C

    2017-06-01

    Pyridine rings are ubiquitous in drug molecules; however, the pre-eminent reaction used to form carbon-carbon bonds in the pharmaceutical industry, the Suzuki-Miyaura cross-coupling reaction, often fails when applied to these structures. This phenomenon is most pronounced in 2-substituted pyridines, and results from the difficulty in preparing, the poor stability of, and low efficiency in reactions of pyridine-2-boronates. We demonstrate that by replacing these boronates with pyridine-2-sulfinates, a cross-coupling process of unrivalled scope and utility is realized. The corresponding 3- and 4-substituted pyridine variants are also efficient coupling partners. In addition, we apply these sulfinates in a library format to the preparation of medicinally relevant derivatives of the drugs varenicline (Chantix) and mepyramine (Anthisan).

  16. 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.

  17. Synthesis of Functionalized [3], [4], [5] and [6]Dendralenes through Palladium-Catalyzed Cross-Couplings of Substituted Allenoates.

    PubMed

    Lippincott, Daniel J; Linstadt, Roscoe T H; Maser, Michael R; Lipshutz, Bruce H

    2017-01-16

    A mild method for the synthesis of highly functionalized [3]-[6]dendralenes is reported, representing a general strategy to diversely substituted higher homologues of the dendralenes. The methodology utilizes allenoates bearing various substitution patterns, along with a wide range of boron and alkenyl nucleophiles that couple under palladium catalysis leading to sp-, sp(2) -, and sp(3) -substituted arrays. Regioselective transformations of the newly formed unsymmetrical dendralene derivatives are demonstrated. The use of micellar catalysis, where water is the global reaction medium, and room temperature reaction conditions, highlights the green nature of this technology.

  18. 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

  19. Palladium-Catalyzed Chemoselective Allylic Substitution, Suzuki-Miyaura Cross-Coupling, and Allene Formation of Bifunctional 2-B(pin)-Substituted Allylic Acetate Derivatives

    PubMed Central

    Kim, Byeong-Seon; Hussain, Mahmud M.; Hussain, Nusrah

    2014-01-01

    A formidable challenge at the forefront of organic synthesis is the control of chemoselectivity to enable the selective formation of diverse structural motifs from a readily available substrate class. Presented herein is a detailed study of chemoselectivity with palladium-based phosphine catalysts and readily available 2-B(pin)-substituted allylic acetates, benzoates, and carbonates. Depending on the choice of reagents, catalysts and reaction conditions, 2-B(pin)-substituted allylic acetates and derivatives can be steered into one of three reaction manifolds: allylic substitution, Suzuki-Miyaura cross-coupling, or elimination to form allenes, all with excellent chemoselectivity. The studies on chemoselectivity of Pd catalysts in their reactivity with boron-bearing allylic acetate derivatives led to the development of diverse and practical reactions with potential utility in synthetic organic chemistry. PMID:25077980

  20. Investigation of an efficient palladium-catalyzed C(sp)-C(sp) cross-coupling reaction using phosphine-olefin ligand: application and mechanistic aspects.

    PubMed

    Shi, Wei; Luo, Yingdong; Luo, Xiancai; Chao, Lei; Zhang, Heng; Wang, Jian; Lei, Aiwen

    2008-11-05

    A pi-acceptor phosphine-electron-deficient olefin ligand was found effective in promoting Pd-catalyzed C(sp)-C(sp) cross-coupling reactions. The new protocol realized the cross-coupling of a broad scope of terminal alkynes and haloalkynes in good to excellent yields with high selectivities. Electron-rich alkynes, which are normally difficult substrates in Glaser couplings, could be employed as either nucleophiles or electrophiles. Alkynes bearing similar substituents, such as n-C5H11CCBr and n-C4H9CCH, which usually suffer from homocoupling side reactions under Cadiot-Chodkiewicz conditions, were successfully cross-coupled in the system. Preliminary kinetic studies revealed that the reaction rate was zero-order in the concentrations of both haloalkynes and terminal alkynes and first order in the loading of Pd(dba)2 and exhibited no obvious dependence on the loading of the copper salt. Control experiments with other phosphines such as PPh3 and DPPF as the ligand were carried out. All the kinetic evidence indicated that the phosphine-olefin ligand facilitated the reductive elimination in the catalytic cycle.

  1. Mizoroki-Heck Cross-coupling Reactions Catalyzed by Dichloro{bis[1,1',1''-(phosphinetriyl)tripiperidine]}palladium Under Mild Reaction Conditions

    PubMed Central

    Oberholzer, Miriam; Frech, Christian M.

    2014-01-01

    Dichloro-bis(aminophosphine) complexes of palladium with the general formula of [(P{(NC5H10)3-n(C6H11)n})2Pd(Cl)2] (where n = 0-2), belong to a new family of easy accessible, very cheap, and air stable, but highly active and universally applicable C-C cross-coupling catalysts with an excellent functional group tolerance. Dichloro{bis[1,1',1''-(phosphinetriyl)tripiperidine]}palladium [(P(NC5H10)3)2Pd(Cl)2] (1), the least stable complex within this series towards protons; e.g. in the form of water, allows an eased nanoparticle formation and hence, proved to be the most active Heck catalyst within this series at 100 °C and is a very rare example of an effective and versatile catalyst system that efficiently operates under mild reaction conditions. Rapid and complete catalyst degradation under work-up conditions into phosphonates, piperidinium salts and other, palladium-containing decomposition products assure an easy separation of the coupling products from catalyst and ligands. The facile, cheap, and rapid synthesis of 1,1',1"-(phosphinetriyl)tripiperidine and 1 respectively, the simple and convenient use as well as its excellent catalytic performance in the Heck reaction at 100 °C make 1 to one of the most attractive and greenest Heck catalysts available. We provide here the visualized protocols for the ligand and catalyst syntheses as well as the reaction protocol for Heck reactions performed at 10 mmol scale at 100 °C and show that this catalyst is suitable for its use in organic syntheses. PMID:24686532

  2. Development of (trimethylsilyl)ethyl ester protected enolates and applications in palladium-catalyzed enantioselective allylic alkylation: intermolecular cross-coupling of functionalized electrophiles.

    PubMed

    Reeves, Corey M; Behenna, Douglas C; Stoltz, Brian M

    2014-05-02

    The development of (trimethylsilyl)ethyl ester protected enolates is reported. The application of this class of compounds in palladium-catalyzed asymmetric allylic alkylation is explored, yielding a variety of α-quaternary six- and seven-membered ketones and lactams. Independent coupling partner synthesis engenders enhanced allyl substrate scope relative to traditional β-ketoester substrates; highly functionalized α-quaternary ketones generated by the union of (trimethylsilyl)ethyl β-ketoesters and sensitive allylic alkylation coupling partners serve to demonstrate the utility of this method for complex fragment coupling.

  3. 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.

  4. Iodination of carbohydrate-derived 1,2-oxazines to enantiopure 5-iodo-3,6-dihydro-2H-1,2-oxazines and subsequent palladium-catalyzed cross-coupling reactions

    PubMed Central

    Medvecký, Michal; Linder, Igor; Schefzig, Luise

    2016-01-01

    Iodination of carbohydrate-derived 3,6-dihydro-2H-1,2-oxazines of type 3 using iodine and pyridine in DMF furnished 5-iodo-substituted 1,2-oxazine derivatives 4 with high efficacy. The alkenyl iodide moiety of 1,2-oxazine derivatives syn-4 and anti-4 was subsequently exploited for the introduction of new functionalities at the C-5 position by applying palladium-catalyzed carbon–carbon bond-forming reactions such as Sonogashira, Heck, or Suzuki coupling reactions as well as a cyanation reaction. These cross-coupling reactions led to a series of 5-alkynyl-, 5-alkenyl-, 5-aryl- and 5-cyano-substituted 1,2-oxazine derivatives being of considerable interest for further synthetic elaborations. This was exemplarily demonstrated by the hydrogenation of syn-21 and anti-24 and by a click reaction of a 5-alkynyl-substituted precursor. PMID:28144363

  5. Efficient access to β-vinylporphyrin derivatives via palladium cross coupling of β-bromoporphyrins with N-tosylhydrazones.

    PubMed

    Campos, Vinicius R; Gomes, Ana T P C; Cunha, Anna C; Neves, Maria da Graça P M S; Ferreira, Vitor F; Cavaleiro, José A S

    2017-01-01

    This work describes a new approach to obtain new β-vinylporphyrin derivatives through palladium-catalyzed cross-coupling reaction of 2-bromo-5,10,15,20-tetraphenylporphyrinatozinc(II) with N-tosylhydrazones. This is the first report of the use of such synthetic methodology in porphyrin chemistry allowing the synthesis of new derivatives, containing β-arylvinyl substituents.

  6. Efficient access to β-vinylporphyrin derivatives via palladium cross coupling of β-bromoporphyrins with N-tosylhydrazones

    PubMed Central

    Campos, Vinicius R; Neves, Maria da Graça P M S; Ferreira, Vitor F

    2017-01-01

    This work describes a new approach to obtain new β-vinylporphyrin derivatives through palladium-catalyzed cross-coupling reaction of 2-bromo-5,10,15,20-tetraphenylporphyrinatozinc(II) with N-tosylhydrazones. This is the first report of the use of such synthetic methodology in porphyrin chemistry allowing the synthesis of new derivatives, containing β-arylvinyl substituents. PMID:28228860

  7. Pd-Catalyzed Decarbonylative Cross-Couplings of Aroyl Chlorides.

    PubMed

    Malapit, Christian A; Ichiishi, Naoko; Sanford, Melanie S

    2017-08-04

    This report describes a method for Pd-catalyzed decarbonylative cross-coupling that enables the conversion of carboxylic acid derivatives to biaryls, aryl amines, aryl ethers, aryl sulfides, aryl boronate esters, and trifluoromethylated arenes. The success of this transformation leverages the Pd(0)/Brettphos-catalyzed decarbonylative chlorination of aroyl chlorides, which can then participate in diverse cross-coupling reactions in situ using the same Pd catalyst.

  8. Synthesis of 3' '-substituted TSAO derivatives with anti-HIV-1 and anti-HIV-2 activity through an efficient palladium-catalyzed cross-coupling approach.

    PubMed

    Lobatón, Esther; Rodríguez-Barrios, Fátima; Gago, Federico; Pérez-Pérez, María-Jesús; De Clercq, Erik; Balzarini, Jan; Camarasa, María-José; Velázquez, Sonsoles

    2002-08-29

    Various synthetic studies for the introduction of several functional groups at position 3' ' of the spiro moiety of TSAO derivatives have been explored. Among them, Stille cross-coupling of 3' '-iodo-TSAO derivatives with different stannanes provided an efficient and straightforward route for the direct and selective functionalization of the 3' '-position of the sultone spiro moiety via carbon-carbon bond formation. The compounds synthesized were evaluated for their inhibitory effect on HIV-1 and HIV-2 replication in cell culture. The introduction of a bromine and particularly an iodine at the 3' '-position conferred the highest anti-HIV-1 activity. In contrast, the presence at this position of (un)substituted vinyl, alkynyl, phenyl, or thienyl groups markedly diminished the anti-HIV-1 activity. Surprisingly, several of the 3' '-alkenyl-substituted TSAO derivatives also gained anti-HIV-2 activity at subtoxic concentrations, an observation that is very unusual for NNRTIs and never observed before for TSAO derivatives. Finally, the anti-HIV-1 activity of some of the 3' '-substituted TSAO derivatives is discussed in light of our recently proposed molecular model of interaction of TSAO derivatives with the interphase between the two subunits of HIV-1 reverse transcriptase.

  9. Diarylmethanes through an Unprecedented Palladium-Catalyzed C−C Cross-Coupling of 1-(Aryl)methoxy-1 H-Benzotriazoles with Arylboronic Acids

    PubMed Central

    Singh, Manish K.

    2015-01-01

    1-(Aryl)methoxy-1H-benzotriazoles (ArCH2OBt) are bench-stable reagents that are prepared readily from 1H-benzotriazol-1-yl-4-methylbenzenesulfonate (BtOTs) and benzylic alcohols. These compounds, which contain a N–O–C bond, undergo cross-coupling with arylboronic acids by C–O bond scission with catalysts that comprise Pd(OAc)2 and biarylphosphine ligands. Such reactivity of ArCH2OBt derivatives, leading to diarylmethanes, has not been described previously and constitutes a new activation of benzylic alcohols. With regard to the various ligands-metal complexes that support catalytic activity, it appears that those with smaller “percent buried volumes” (%Vbur) provide better outcomes. This factor has been evaluated in the initial optimization studies and in further reactions with difficult coupling partners. Ligand electronics of the biaryl moiety seem to play a lesser role in this type of reaction. The bis-coordinating bis[(2-diphenylphosphino)phenyl]ether appears to be suitable to improve the yields of low-yielding reactions. PMID:27134687

  10. 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%).

  11. Novel method for the synthesis of enamines by palladium catalyzed amination of alkenyl bromides.

    PubMed

    Barluenga, José; Fernández, M Alejandro; Aznar, Fernando; Valdés, Carlos

    2002-10-21

    The intermolecular palladium catalyzed cross-coupling reaction between secondary amines and alkenyl bromides is described for the first time, giving rise to enamines with very high yields and regioselectivity.

  12. 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.

  13. Highly efficient palladium-catalyzed hydrostannation of ethyl ethynyl ether.

    PubMed

    Andrews, Ian P; Kwon, Ohyun

    2008-12-08

    The palladium-catalyzed hydrostannation of acetylenes is widely exploited in organic synthesis as a means of forming vinyl stannanes for use in palladium-catalyzed cross-coupling reactions. Application of this methodology to ethyl ethynyl ether results in an enol ether that is challenging to isolate from the crude reaction mixture because of incompatibility with typical silica gel chromatography. Reported here is a highly efficient procedure for the palladium-catalyzed hydrostannation of ethyl ethynyl ether using 0.1% palladium(0) catalyst and 1.0 equiv of tributyltin hydride. The product obtained is a mixture of regioisomers that can be carried forward with exclusive reaction of the beta-isomer. This method is highly reproducible; relative to previously reported procedures, it is more economical and involves a more facile purification procedure.

  14. 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.

  15. 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

  16. Palladium-Catalyzed Arylation of Fluoroalkylamines.

    PubMed

    Brusoe, Andrew T; Hartwig, John F

    2015-07-08

    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.

  17. Palladium-Catalyzed Synthesis of N-Aryl Carbamates

    PubMed Central

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

    2013-01-01

    An efficient synthesis of aryl carbamates was achieved by introducing alcohols into the reaction of palladium-catalyzed cross-coupling of ArX (X = Cl, OTf) with sodium cyanate. The use of aryl triflates as electrophilic components in this transformation allowed for an expanded substrate scope for direct synthesis of aryl isocyanates. This methodology provides direct access to major carbamate protecting groups, S-thiocarbamates, and diisocyanate precursors to polyurethane materials. PMID:23441814

  18. 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

  19. 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

  20. Mechanism of Cu/Pd-catalyzed decarboxylative cross-couplings: a DFT investigation.

    PubMed

    Fromm, Andreas; van Wüllen, Christoph; Hackenberger, Dagmar; Gooßen, Lukas J

    2014-07-16

    The reaction mechanism of decarboxylative cross-couplings of benzoates with aryl halides to give biaryls, which is cooperatively catalyzed by copper/palladium systems, was investigated with DFT methods. The geometries and energies of all starting materials, products, intermediates, and transition states of the catalytic cycle were calculated for the two model reactions of potassium 2- and 4-fluorobenzoate with bromobenzene in the presence of a catalyst system consisting of copper(I)/1,10-phenanthroline and the anionic monophosphine palladium complex [Pd(PMe3)Br](-). Several neutral and anionic pathways were compared, and a reasonable catalytic cycle was identified. The key finding is that the transmetalation has a comparably high barrier as the decarboxylation, which was previously believed to be solely rate-determining. The electronic activation energy of the transmetalation is rather reasonable, but the free energy loss in the initial Cu/Pd adduct formation is high. These results suggested that research aimed at further improving the catalyst should target potentially bridging bidentate ligands likely to assist in the formation of bimetallic intermediates. Experimental studies confirm this somewhat counterintuitive prediction. With a bidentate, potentially bridging ligand, designed to support the formation of bimetallic adducts, the reaction temperature for decarboxylative couplings was reduced by 70 °C to only 100 °C.

  1. Pd-catalyzed decarboxylative cross coupling of potassium polyfluorobenzoates with aryl bromides, chlorides, and triflates.

    PubMed

    Shang, Rui; Xu, Qing; Jiang, Yuan-Ye; Wang, Yan; Liu, Lei

    2010-03-05

    Pd-catalyzed decarboxylative cross coupling of potassium polyfluorobenzoates with aryl bromides, chlorides, and triflates is achieved by using diglyme as the solvent. The reaction is useful for synthesis of polyfluorobiaryls from readily accessible and nonvolatile polyfluorobenzoate salts. Unlike the Cu-catalyzed decarboxylation cross coupling where oxidative addition is the rate-limiting step, in the Pd-catalyzed version decarboxylation is the rate-limiting step.

  2. Iron-catalyzed cross-coupling reactions of alkyl Grignards with aryl sulfamates and tosylates.

    PubMed

    Agrawal, Toolika; Cook, Silas P

    2013-01-04

    The iron-catalyzed cross-coupling of aryl sulfamates and tosylates has been achieved with primary and secondary alkyl Grignards. This study of iron-catalyzed cross-coupling reactions also examines the isomerization and β-hydride elimination problems that are associated with the use of isopropyl nucleophiles. While a variety of iron sources were competent in the reaction, the use of FeF(3)•3H(2)O was critical to minimize nucleophile isomerization.

  3. Palladium-Catalysed Cross-Coupling Reactions Controlled by Noncovalent Zn⋅⋅⋅N Interactions.

    PubMed

    Kadri, Mohamed; Hou, Jingran; Dorcet, Vincent; Roisnel, Thierry; Bechki, Lazhar; Miloudi, Abdellah; Bruneau, Christian; Gramage-Doria, Rafael

    2017-04-11

    Non-covalent interactions between halopyridine substrates and catalytically inert building blocks, namely zinc(II)-porphyrins and zinc(II)-salphens, influence the catalytic outcome of Suzuki-Miyaura and Mizoroki-Heck palladium-catalysed cross-coupling reactions. The weak Zn⋅⋅⋅N interactions between halopyridine substrates and zinc(II)-containing porphyrins and salphens, respectively, were studied by a combination of (1) H NMR spectroscopy, UV/Vis studies, Job-Plot analysis and, in some cases, X-ray diffraction studies. Additionally, the former studies revealed unique supramolecular polymeric and dimeric rearrangements in the solid state featuring weak Br⋅⋅⋅N (halogen bonding), C-H⋅⋅⋅π, Br⋅⋅⋅π and π⋅⋅⋅π interactions. The reactivity of halopyridine substrates in homogeneous palladium-catalysed cross-coupling reactions was found to correlate with the binding strength between the zinc(II)-containing scaffolds and the corresponding halopyridine. Such observation is explained by the unfavourable formation of inactive over-coordinated halopyridine⋅⋅⋅palladium species. The presented approach is particularly appealing for those cases in which substrates and/or products deactivate (or partially poison) a transition-metal catalyst. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. 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.

  5. Chemoselective and Sequential Palladium-Catalyzed Couplings for the Generation of Stilbene Libraries via Immobilized Substrates.

    PubMed

    Traficante, Carla I; Fagundez, Catherine; Serra, Gloria L; Mata, Ernesto G; Delpiccolo, Carina M L

    2016-05-09

    A versatile palladium-catalyzed tandem synthetic sequence to afford E-stilbenes libraries has been developed. Excellent regio- and stereocontrol have been achieved by means of the sequence of Hiyama and Heck cross-couplings. Undesirable homocoupling byproducts were avoided employing immobilized substrates.

  6. Palladium-catalyzed phosphonylation: synthesis of C3-, C4-, and C5-phosphonylated pyrazoles.

    PubMed

    Tran, Gaël; Gomez Pardo, Domingo; Tsuchiya, Tomoki; Hillebrand, Stefan; Vors, Jean-Pierre; Cossy, Janine

    2013-11-01

    A palladium-catalyzed cross-coupling between 3-, 4-, and 5-halo-pyrazoles and H-phosphonates, H-phosphinates, and secondary phosphine oxides has been developed. This coupling reaction constitutes the first general method allowing the introduction of a great diversity of phosphorus substituents on the different carbons of the pyrazole ring in a one-step process.

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

    PubMed

    Nishikata, Takashi; Abela, Alexander R; Huang, Shenlin; Lipshutz, Bruce H

    2016-01-01

    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.

  8. 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

  9. 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

  10. 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

  11. Palladium-Catalyzed α-Arylation of Aryl Acetic Acid Derivatives via Dienolate Intermediates with Aryl Chlorides and Bromides

    PubMed Central

    2016-01-01

    To date, examples of α-arylation of carboxylic acids remain scarce. Using a deprotonative cross-coupling process (DCCP), a method for palladium-catalyzed γ-arylation of aryl acetic acids with aryl halides has been developed. This protocol is applicable to a wide range of aryl bromides and chlorides. A procedure for the palladium-catalyzed α-arylation of styryl acetic acids is also described. PMID:25582024

  12. 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.

  13. 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.

  14. 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

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

    PubMed

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

    2015-03-10

    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.

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

    PubMed

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

    2012-09-21

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

  17. Iron-catalyzed cross-coupling of imidoyl chlorides with Grignard reagents.

    PubMed

    Ottesen, Lars K; Ek, Fredrik; Olsson, Roger

    2006-04-27

    [reaction: see text] A general, high yielding rapid iron-catalyzed cross-coupling reaction between Grignard reagents and imidoyl chlorides is described. These reactions are typically completed within 5 min, resulting in high yields of 71-96% using 5% iron catalyst in a THF-NMP solvent mixture. Functionalized imidoyl chlorides (e.g., R = CO(2)Me) gave excellent yields (89%).

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

    PubMed Central

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

    2010-01-01

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

  19. Palladium-catalyzed substitution of allylic fluorides.

    PubMed

    Hazari, Amaruka; Gouverneur, Véronique; Brown, John M

    2009-01-01

    As unusual substrates for the Tsuji-Trost allylation reaction, allylic fluorides are responsive to palladium-catalyzed substitution. Their activity towards this reaction fits in the series OCO(2)Me>OBz>F>OAc. The classic stereoretention mechanism that involves sequential inversions does not operate in this case. Several distinct cases are considered.

  20. Intensification of heterogeneously catalyzed Suzuki-Miyaura cross-coupling reaction using ultrasound: Understanding effect of operating parameters.

    PubMed

    Sancheti, Sonam V; Gogate, Parag R

    2017-01-27

    Palladium-catalyzed Suzuki-Miyaura cross-coupling reaction is a significant reaction for obtaining industrially important products. The current research work deals with intensification of reaction of 4-bromoanisole and phenylboronic acid catalyzed with 5wt% Pd/C (5% by weight Pd supported on C available as commercial catalyst) using ultrasound and more importantly, without use of any additional phase transfer catalyst. Heterogeneous catalyst has been selected in the present work so as to harness the benefits of easy separation and the possible limitations of heterogeneous operation are minimized by introducing ultrasonic irradiations. The effect of operating parameters such as ultrasound power, temperature, catalyst loading and molar ratio on the progress of reaction has been investigated. It has been observed that an optimum power, temperature and catalyst loading exist for maximum benefits whereas higher molar ratio was found to be favourable for the progress of the reaction. Also, the use of ultrasound reduced the reaction time from 70min required in conventional approach to only 35min under conditions of frequency of 22kHz, power dissipation of 40W and catalyst loading as 1.5mol% (refers to total quantum of catalyst used in the work) in ethanol-water system under ambient conditions. The work also demonstrated successful results at ten times higher volume as compared to the normally used volumes in the case of simple ultrasonic horn. Overall, the work has successfully demonstrated process intensification benefits obtained due to the use of ultrasound for heterogeneously catalyzed Suzuki-Miyaura cross-coupling reaction.

  1. 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)

  2. 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)

  3. Pd- and Ni-catalyzed cross-coupling reactions in the synthesis of organic electronic materials

    PubMed Central

    Xu, Shiqing; Kim, Eun Hoo; Wei, Alexander; Negishi, Ei-ichi

    2014-01-01

    Organic molecules and polymers with extended π-conjugation are appealing as advanced electronic materials, and have already found practical applications in thin-film transistors, light emitting diodes, and chemical sensors. Transition metal (TM)-catalyzed cross-coupling methodologies have evolved over the past four decades into one of the most powerful and versatile methods for C–C bond formation, enabling the construction of a diverse and sophisticated range of π-conjugated oligomers and polymers. In this review, we focus our discussion on recent synthetic developments of several important classes of π-conjugated systems using TM-catalyzed cross-coupling reactions, with a perspective on their utility for organic electronic materials. PMID:27877696

  4. Pd- and Ni-catalyzed cross-coupling reactions in the synthesis of organic electronic materials.

    PubMed

    Xu, Shiqing; Kim, Eun Hoo; Wei, Alexander; Negishi, Ei-Ichi

    2014-08-01

    Organic molecules and polymers with extended π-conjugation are appealing as advanced electronic materials, and have already found practical applications in thin-film transistors, light emitting diodes, and chemical sensors. Transition metal (TM)-catalyzed cross-coupling methodologies have evolved over the past four decades into one of the most powerful and versatile methods for C-C bond formation, enabling the construction of a diverse and sophisticated range of π-conjugated oligomers and polymers. In this review, we focus our discussion on recent synthetic developments of several important classes of π-conjugated systems using TM-catalyzed cross-coupling reactions, with a perspective on their utility for organic electronic materials.

  5. Pd- and Ni-catalyzed cross-coupling reactions in the synthesis of organic electronic materials

    NASA Astrophysics Data System (ADS)

    Xu, Shiqing; Hoo Kim, Eun; Wei, Alexander; Negishi, Ei-ichi

    2014-08-01

    Organic molecules and polymers with extended π-conjugation are appealing as advanced electronic materials, and have already found practical applications in thin-film transistors, light emitting diodes, and chemical sensors. Transition metal (TM)-catalyzed cross-coupling methodologies have evolved over the past four decades into one of the most powerful and versatile methods for C-C bond formation, enabling the construction of a diverse and sophisticated range of π-conjugated oligomers and polymers. In this review, we focus our discussion on recent synthetic developments of several important classes of π-conjugated systems using TM-catalyzed cross-coupling reactions, with a perspective on their utility for organic electronic materials.

  6. 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

  7. Pentafluorophenyl imidato palladium(II) complexes: catalysts for Suzuki cross-coupling reactions.

    PubMed

    Ruiz, José; Vicente, Consuelo; Cutillas, Natalia; Pérez, José

    2005-06-07

    Novel N-bonded imidato complexes of general formula [Pd(N-N)(C6F5)(imidate)](imidate = maleimidate, succinimidate or phthalimidate; N-N = 2,2'-bipyridine (bipy), 4,4'-dimethyl-2,2'-bipyridine (Me2bipy) or N,N,N',N'-tetramethylethylenediamine (tmeda)), [NBu4][Pd(C6F5)(H2O)(succinimidate)2] and [NBu4][Pd(C6F5)(L)(succinimidate)2](L = PPh3 or t-BuNC) have been synthesised. These complexes are air-, light- and moisture-stable. The crystal structures of [Pd(tmeda)(C6F5)(maleimidate)].H2O.0.5CHCl3, [NBu4][Pd(C6F5)(H2O)(succinimidate)2].H2O and [NBu4][Pd(C6F5)(t-BuNC)(succinimidate)2].2H2O have been determined by X-ray diffraction. Many of these new complexes are shown to be active phosphine-free palladium catalysts/precatalysts for the Suzuki cross-coupling reactions of aryl bromides and aryl chlorides with phenylboronic acid.

  8. Palladium-Catalyzed Fluorosulfonylvinylation of Organic Iodides.

    PubMed

    Zha, Gao-Feng; Zheng, Qinheng; Leng, Jing; Wu, Peng; Qin, Hua-Li; Sharpless, K Barry

    2017-03-29

    A palladium-catalyzed fluorosulfonylvinylation reaction of organic iodides is described. Catalytic Pd(OAc)2 with a stoichiometric amount of silver(I) trifluoroacetate enables the coupling process between either an (hetero)aryl or alkenyl iodide with ethenesulfonyl fluoride (ESF). The method is demonstrated in the successful syntheses of eighty-eight otherwise difficult to access compounds, in up to 99 % yields, including the unprecedented 2-heteroarylethenesulfonyl fluorides and 1,3-dienylsulfonyl fluorides.

  9. QuadraPure-Supported Palladium Nanocatalysts for Microwave-Promoted Suzuki Cross-Coupling Reaction under Aerobic Condition

    PubMed Central

    Loh, Poh Lee; Juan, Joon Ching; Yarmo, Mohd Ambar; Yusop, Rahimi M.

    2014-01-01

    Cross-linked resin-captured palladium (XL-QPPd) was readily prepared by simple physical adsorption onto the high loading QuadraPure macroporous resin and a subsequent reduction process. To enhance the mechanical stability, entrapped palladium nanocatalysts were cross-linked with succinyl chloride. Both transmission electron microscopy images and X-ray diffraction analysis revealed that the palladium nanoparticles were well dispersed with diameters ranging in 4–10 nm. The catalyst performed good catalytic activity in microwave-promoted Suzuki cross-coupling reactions in water under aerobic condition with mild condition by using various aryl halides and phenylboronic acid. In addition, the catalyst showed an excellent recyclability without significant loss of catalytic activity. PMID:25054185

  10. QuadraPure-supported palladium nanocatalysts for microwave-promoted Suzuki cross-coupling reaction under aerobic condition.

    PubMed

    Liew, Kin Hong; Loh, Poh Lee; Juan, Joon Ching; Yarmo, Mohd Ambar; Yusop, Rahimi M

    2014-01-01

    Cross-linked resin-captured palladium (XL-QPPd) was readily prepared by simple physical adsorption onto the high loading QuadraPure macroporous resin and a subsequent reduction process. To enhance the mechanical stability, entrapped palladium nanocatalysts were cross-linked with succinyl chloride. Both transmission electron microscopy images and X-ray diffraction analysis revealed that the palladium nanoparticles were well dispersed with diameters ranging in 4-10 nm. The catalyst performed good catalytic activity in microwave-promoted Suzuki cross-coupling reactions in water under aerobic condition with mild condition by using various aryl halides and phenylboronic acid. In addition, the catalyst showed an excellent recyclability without significant loss of catalytic activity.

  11. Total Synthesis of Piericidin A1. Application of a Modified Negishi Carboalumination-Nickel-Catalyzed Cross-Coupling

    PubMed Central

    Lipshutz, Bruce H.; Amorelli, Benjamin

    2012-01-01

    A total synthesis of the mitochondrial complex I inhibitor piericidin A1 is described. It features a unique strategy for the key disconnection, highlighting a modified Negishi carboalumination/Ni-catalyzed cross-coupling on a polyenyne precursor. PMID:19138148

  12. Palladium mediated intramolecular multiple C-X/C-H cross coupling and C-H activation: synthesis of carbazole alkaloids calothrixin B and murrayaquinone A.

    PubMed

    Kaliyaperumal, Srinivasan A; Banerjee, Shyamapada; U K, Syam Kumar

    2014-08-28

    Straightforward palladium mediated syntheses of calothrixin B and murrayaquinone A are described. Regioselective palladium mediated intramolecular multiple C-X/C-H cross coupling reaction on N-(4-((2-bromophenyl)amino)-2,5-dimethoxybenzyl)-N-(2-iodophenyl)acetamide followed by CAN oxidation afforded calothrixin B in excellent yield in two steps. A linear synthesis has also been developed for calothrixin B. Utilizing C-H functionalization as well as palladium mediated intramolecular C-X/C-H cross coupling reaction, murrayaquinone A synthesis was achieved. Overall, these synthetic methodologies provide an expedient entry to these biologically active alkaloids in a short reaction sequence.

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-02-17

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

  15. Insight into Transmetalation Enables Cobalt-Catalyzed Suzuki–Miyaura Cross Coupling

    PubMed Central

    2016-01-01

    Among the fundamental transformations that comprise a catalytic cycle for cross coupling, transmetalation from the nucleophile to the metal catalyst is perhaps the least understood. Optimizing this elementary step has enabled the first example of a cobalt-catalyzed Suzuki–Miyaura cross coupling between aryl triflate electrophiles and heteroaryl boron nucleophiles. Key to this discovery was the preparation and characterization of a new class of tetrahedral, high-spin bis(phosphino)pyridine cobalt(I) alkoxide and aryloxide complexes, (iPrPNP)CoOR, and optimizing their reactivity with 2-benzofuranylBPin (Pin = pinacolate). Cobalt compounds with small alkoxide substituents such as R = methyl and ethyl underwent swift transmetalation at 23 °C but also proved kinetically unstable toward β–H elimination. Secondary alkoxides such as R = iPr or CH(Ph)Me balanced stability and reactivity. Isolation and structural characterization of the product following transmetalation, (iPrPNP)Co(2-benzofuranyl), established a planar, diamagnetic cobalt(I) complex, demonstrating the high- and low-spin states of cobalt(I) rapidly interconvert during this reaction. The insights from the studies in this elementary step guided selection of appropriate reaction conditions to enable the first examples of cobalt-catalyzed C–C bond formation between neutral boron nucleophiles and aryl triflate electrophiles, and a model for the successful transmetalation reactivity is proposed. PMID:28058283

  16. 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

  17. A Mild, Palladium-Catalyzed Method for the Dehydrohalogenation of Alkyl Bromides: Synthetic and Mechanistic Studies

    PubMed Central

    Bissember, Alex C.; Levina, Anna

    2012-01-01

    We have exploited a typically undesired elementary step in cross-coupling reactions, β-hydride elimination, to accomplish palladium-catalyzed dehydrohalogenations of alkyl bromides to form terminal olefins. We have applied this method, which proceeds in excellent yield at room temperature in the presence of a variety of functional groups, to a formal total synthesis of (R)-mevalonolactone. Our mechanistic studies establish that the rate-determining step can vary with the structure of the alkyl bromide, and, most significantly, that L2PdHBr (L=phosphine), an often-invoked intermediate in palladium-catalyzed processes such as the Heck reaction, is not an intermediate in the active catalytic cycle. PMID:22905894

  18. 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. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. 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

  20. Palladium-Catalyzed Aminocarbonylation of Allylic Alcohols.

    PubMed

    Li, Haoquan; Neumann, Helfried; Beller, Matthias

    2016-07-11

    A benign and efficient palladium-catalyzed aminocarbonylation reaction of allylic alcohols is presented. The generality of this novel process is demonstrated by the synthesis of β,γ-unsaturated amides including aliphatic, cinnamyl, and terpene derivatives. The choice of ligand is crucial for optimal carbonylation processes: Whereas in most cases the combination of PdCl2 with Xantphos (L6) gave best results, sterically hindered substrates performed better in the presence of simple triphenylphosphine (L10), and primary anilines gave the best results using cataCXium® PCy (L8). The reactivity of the respective catalyst system is significantly enhanced by addition of small amounts of water. Mechanistic studies and control experiments revealed a tandem allylic alcohol amination/C-N bond carbonylation reaction sequence.

  1. Combination of Microwave Reactions with Fluorous Separations in the Palladium-Catalyzed Synthesis of Aryl Sulfides

    PubMed Central

    Zhang, Wei; Lu, Yimin; Chen, Christine Hiu-Tung

    2007-01-01

    Coupling of microwave reactions with fluorous separations can dramatically increase the efficiency of high-speed synthesis. Described in this paper is a fluorous synthesis of aryl sulfides by palladium-catalyzed cross-coupling of aryl perfluoroalkylsulfonates (C8F17O2SOAr) with thiols (RSH) under microwave irradiation. Fluorous solid-phase extractions (F-SPE) are employed for the purification of reaction mixtures. No fluorous solvents are involved in reaction and separation processes. The fluorous synthesis is further extended to the multi-step synthesis of substituted hydantoin and amide scaffolds. PMID:14870851

  2. A Bulky Biaryl Phosphine Ligand Allows for Palladium-Catalyzed Amidation of Five-Membered Heterocycles as Electrophiles**

    PubMed Central

    Su, Mingjuan; Buchwald, Stephen L.

    2012-01-01

    Palladium-catalyzed amidation of five-membered heterocyclic bromides that contain multiple heteroatoms was achieved for the first time using the Pd/1 catalyst system. This system allows for efficient access to N-arylated imidazoles, pyrazoles, thiazoles, pyrroles, and thiophenes in moderate to excellent yield. Experimental results and DFT calculations point to the need for electron-rich and especially sterically demanding biaryl phosphine ligand to promote these difficult cross-coupling reactions. PMID:22473747

  3. Efficient and selective synthesis of 6,7-Dehydrostipiamide via Zr-catalyzed asymmetric carboalumination and Pd-catalyzed cross-coupling of organozincs.

    PubMed

    Zeng, Xingzhong; Zeng, Fanxing; Negishi, Ei-ichi

    2004-09-16

    [structure: see text] 6,7-Dehydrostipiamide has been synthesized in 23% yield in 15 steps in the longest linear sequence through the application of the Zr-catalyzed asymmetric carboalumination and the Pd-catalyzed organozinc cross-coupling in addition to the Brown crotylboration, the Corey-Peterson olefination, and the Corey-Fuchs reaction for carbon-carbon bond formation.

  4. Efficient batch and continuous flow Suzuki cross-coupling reactions under mild conditions, catalysed by polyurea-encapsulated palladium (II) acetate and tetra-n-butylammonium salts.

    PubMed

    Lee, Connie K Y; Holmes, Andrew B; Ley, Steven V; McConvey, Ian F; Al-Duri, Bushra; Leeke, Gary A; Santos, Regina C D; Seville, Jonathan P K

    2005-04-28

    Suzuki cross-coupling reactions are effected in both conventional organic solvents, under continuous flow conditions at 70 degree C, and in batch mode in supercritical carbon dioxide (scCO2), at temperatures as low as 40 degrees C in the presence of palladium(II) acetate microencapsulated in polyurea [PdEnCat] and tetra-n-butylammonium salts.

  5. Alkyne Elementometalation–Pd-Catalyzed Cross-Coupling. Towards Synthesis of Various Types of Acyclic Alkenes in High Yields, Efficiently, Selectively, Economically, and Safely—“Green” Way

    PubMed Central

    Wang, Guangwei; Rao, Honghua; Xu, Zhaoqing

    2010-01-01

    Palladium-catalyzed cross-coupling reactions, especially those involving Zn, Al, Zr (Negishi coupling) and B (Suzuki coupling), collectively have brought about “revolutionary” changes in organic synthesis. Thus, two regio- and stereodefined carbon groups generated as R1M (M = Zn, Al, B, Cu, Zr, etc.) and R2X (X = I, Br, OTs, etc.) may now be cross-coupled to give R1–R2 with essentially full retention of all structural features. For alkene syntheses, alkyne elementometalation reactions including hydrometalation (B, Al, Zr, etc.), carbometalation (Cu, Al–Zr, etc.), and haloboration (BX3 where X is Cl, Br, and I) have proven to be critically important. Some representative examples of highly efficient and selective (≥98%) syntheses of di-, tri- and oligoenes containing regio- and stereodefined di- and trisubstituted alkenes of all conceivable types will be discussed with emphasis on those of natural products. Some interesting but undesirable cases involving loss of the initial structural identities of the alkenyl groups are attributable to the formation of allylpalladium species, which must be either tamed or avoided. Some such examples involving the synthesis of 1,3-, 1,4-, and 1,5-dienes will also be discussed. PMID:20465291

  6. Synthesis of zwitterionic palladium complexes and their application as catalysts in cross-coupling reactions of aryl, heteroaryl and benzyl bromides with organoboron reagents in neat water.

    PubMed

    Ramakrishna, V; Dastagiri Reddy, N

    2017-07-04

    N-(3-Chloro-2-quinoxalinyl)-N'-arylimidazolium salts (aryl = 2,6-diisopropylphenyl [HL1Cl]Cl, aryl = mesityl [HL2Cl]Cl) have been synthesized by treating 2,3-dichloroquinoxaline with the corresponding N'-arylimidazole in neat water. Facile reactions of these imidazolium salts with Pd(PPh3)4 and Pd2(dba)3/PPh3 (dba = dibenzyledene acetone) at 50 °C have afforded zwitterionic palladium(ii) complexes [Pd(HL1)(PPh3)Cl2] (I) and [Pd(HL2)(PPh3)Cl2] (II) in excellent yields. I and II have been tested for their ability to catalyze Suzuki-Miyaura cross coupling (SMC) reactions in neat water/K2CO3 and are found to be highly active for carrying out these reactions between aryl bromides and organoboron reagents. Furthermore, the scope of the catalyst I was also examined by employing (hetero)aryl bromides, hydrophilic aryl bromides, benzyl bromides and various organoboron reagents. More than 80 aryl/benzyl bromide-arylboronic acid combinations were screened in neat water/K2CO3 and it was found that I was a versatile catalyst, which produced biaryls/diarylmethanes in excellent yields. A TON of 82 000 was achieved by using I. Studies on the mechanism have also been carried out to investigate the involvement of carbene complexes in the catalytic path. Poison tests and a two-phase test were also conducted and the results are reported.

  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. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Impact of copper-catalyzed cross-coupling reactions in natural product synthesis: the emergence of new retrosynthetic paradigms.

    PubMed

    Evano, Gwilherm; Theunissen, Cédric; Pradal, Alexandre

    2013-12-01

    Copper-catalyzed Ullmann-Goldberg-type cross-coupling reactions have undergone nothing short of a renaissance over the last decade and an impressive number of procedures are now available for the formation of C-N, C-O and C-S bonds with remarkable efficiencies and surgical precision. These reactions have been recently integrated into natural product synthesis, which clearly resulted in the emergence of new retrosynthetic paradigms and bond disconnections. The impact of copper-catalyzed cross-coupling reactions in natural product synthesis will be overviewed in this article with an emphasis on the evolution of strategies due to copper catalysis, mostly by comparison with alternative tactics and their relative efficiencies.

  9. Catalyst activation, deactivation, and degradation in palladium-mediated Negishi cross-coupling reactions.

    PubMed

    Böck, Katharina; Feil, Julia E; Karaghiosoff, Konstantin; Koszinowski, Konrad

    2015-03-27

    Pd-mediated Negishi cross-coupling reactions were studied by a combination of kinetic measurements, electrospray-ionization (ESI) mass spectrometry, (31)P NMR and UV/Vis spectroscopy. The kinetic measurements point to a rate-determining oxidative addition. Surprisingly, this step seems to involve not only the Pd catalyst and the aryl halide substrate, but also the organozinc reagent. In this context, the ESI-mass spectrometric observation of heterobimetallic Pd-Zn complexes [L2 PdZnR](+) (L=S-PHOS, R=Bu, Ph, Bn) is particularly revealing. The inferred presence of these and related neutral complexes with a direct Pd-Zn interaction in solution explains how the organozinc reagent can modulate the reactivity of the Pd catalyst. Previous theoretical calculations by González-Pérez et al. (Organometallics- 2012, 31, 2053) suggest that the complexation by the organozinc reagent lowers the activity of the Pd catalyst. Presumably, a similar effect also causes the rate decrease observed upon addition of ZnBr2 . In contrast, added LiBr apparently counteracts the formation of Pd-Zn complexes and restores the high activity of the Pd catalyst. At longer reaction times, deactivation processes due to degradation of the S-PHOS ligand and aggregation of the Pd catalyst come into play, thus further contributing to the appreciable complexity of the title reaction.

  10. I₂-TBHP-catalyzed oxidative cross-coupling of N-sulfonyl hydrazones and isocyanides to 5-aminopyrazoles.

    PubMed

    Senadi, Gopal Chandru; Hu, Wan-Ping; Lu, Ting-Yi; Garkhedkar, Amol Milind; Vandavasi, Jaya Kishore; Wang, Jeh-Jeng

    2015-03-20

    I2-TBHP-catalyzed oxidative cross coupling of N-sulfonyl hydrazones with isocyanides has been realized for the synthesis of 5-aminopyrazoles through formal [4 + 1] annulation via in situ azoalkene formation. Notable features are the metal/alkyne-free strategy, C-C and C-N bond formation, atom economy, catalytic I2, broad functional group tolerance, good reaction yields, shorter time, and also applicability to one-pot methodology.

  11. Pd(OAc)2-catalyzed fluoride-free cross-coupling reactions of arylsiloxanes with aryl bromides in aqueous medium.

    PubMed

    Shi, Shengyin; Zhang, Yuhong

    2007-07-20

    Mild conditions have been developed to achieve the Pd(OAc)2-catalyzed fluoride-free cross-coupling between the aryl bromides and arylsiloxanes in good to high yields in aqueous medium. The success of the reactions requires the presence of poly(ethylene glycol) (PEG) and 3 equiv of sodium hydroxide. The product was easily separated with ethyl ether extraction, and the catalytic system can be reused eight times with high efficiency.

  12. Ligand-Assisted Gold-Catalyzed Cross-Coupling with Aryldiazonium Salts: Redox Gold Catalysis without an External Oxidant.

    PubMed

    Cai, Rong; Lu, Mei; Aguilera, Ellen Y; Xi, Yumeng; Akhmedov, Novruz G; Petersen, Jeffrey L; Chen, Hao; Shi, Xiaodong

    2015-07-20

    Gold-catalyzed C(sp)-C(sp(2)) and C(sp(2))-C(sp(2)) cross-coupling reactions are accomplished with aryldiazonium salts as the coupling partner. With the assistance of bpy ligand, gold(I) species were oxidized to gold(III) by diazonium without any external oxidants. Monitoring the reaction with NMR and ESI-MS provided strong evidence for the nitrogen extrusion followed by Au(III) reductive elimination as the key step.

  13. Selective Formation of Secondary Amides via the Copper-Catalyzed Cross-Coupling of Alkylboronic Acids with Primary Amides

    PubMed Central

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

    2014-01-01

    For the first time, a general catalytic procedure for the cross coupling of primary amides and alkylboronic acids is demonstrated. The key to the success of this reaction was the identification of a mild base (NaOSiMe3) and oxidant (di-tert-butyl peroxide) to promote the copper-catalyzed reaction in high yield. This transformation provides a facile, high-yielding method for the mono-alkylation of amides. PMID:23611591

  14. 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.

  15. 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

  16. Cobalt-Catalyzed Cross-Coupling of Grignards with Allylic and Vinylic Bromides: Use of Sarcosine as a Natural Ligand.

    PubMed

    Frlan, Rok; Sova, Matej; Gobec, Stanislav; Stavber, Gaj; Časar, Zdenko

    2015-08-07

    Sarcosine was discovered to be an excellent ligand for cobalt-catalyzed carbon-carbon cross-coupling of Grignard reagents with allylic and vinylic bromides. The Co(II)/sarcosine catalytic system is shown to perform efficiently when phenyl and benzyl Grignards are coupled with alkenyl bromides. Notably, previously unachievable Co-catalyzed coupling of allylic bromides with Grignards to linearly coupled α-products was also realized with Co(II)/sarcosine catalyst. This method was used for efficient preparation of the key intermediate in an alternative synthesis of the antihyperglycemic drug sitagliptin.

  17. Nickel-catalyzed cross-coupling of aryl phosphates with arylboronic acids.

    PubMed

    Chen, Hu; Huang, Zhongbin; Hu, Xiaoming; Tang, Guo; Xu, Pengxiang; Zhao, Yufen; Cheng, Chien-Hong

    2011-04-01

    The Suzuki-Miyaura cross-coupling of aryl phosphates using Ni(PCy(3))(2)Cl(2) as an inexpensive, bench-stable catalyst is described. Broad substrate scope and high efficiency are demonstrated by the syntheses of more than 40 biaryls and by constructing complex organic molecules. The poor reactivity of aryl phosphates relative to aryl halides is successfully employed to construct polyarenes by selective cross-coupling using Pd and Ni catalysts.

  18. Carbon-supported palladium and ruthenium nanoparticles: application as catalysts in alcohol oxidation, cross-coupling and hydrogenation reactions.

    PubMed

    García-Suárez, Eduardo J; Lara, Patricia; García, Ana B; Philippot, Karine

    2013-11-01

    In the last fifteen-years, the application of metal nanoparticles as catalysts in organic synthesis has received a renewed interest. Therefore, much attention is currently being paid to the synthesis of metal nanoparticles in order to achieve the control of their characteristics in terms of size, shape and surface chemistry. Besides this, the recyclability as well as the recovery from the reaction medium still remain the major drawbacks to widespread the use of nanoparticles in catalysis. To overcome these problems, the immobilization of metal nanoparticles on solid supports appears as a promising alternative. In that context, carbon materials offer several advantages as solid supports such as availability, relatively low cost, high mechanical strength, chemical stability, and a pore structure along with an attractive surface chemistry which allows easy modifications, such as its functionalization, to suit the nanoparticles immobilization needs. Among the transition metals Palladium and Ruthenium are widely employed as efficient catalysts in many reactions. Herein, the most recent advances, from recent papers and patents, in relation to the preparation of carbon-supported Pd or Ru nanoparticles systems as well as their application as catalysts in alcohol oxidation, cross-coupling or hydrogenation reactions, are reviewed.

  19. Palladium Catalyst Supported on Zeolite for Cross-coupling Reactions: An Overview of Recent Advances.

    PubMed

    Kumbhar, Arjun

    2017-02-01

    Over the last 30-40 years, Pd-catalyzed C-C bond-forming reactions have gained immense importance for their use in synthesis of biologically and pharmaceutically important organic fragments. Heterogeneous Pd catalysts supported on porous materials, especially zeolites, have many advantages as they have high surface area with tunable acidity and basicity, hydrophobic and hydrophilic character, shape and size selectivity, as well as chemical and thermal stability. They also offer very easy recovery and reusability. This review covers the literature published on the synthesis and characterization of Pd catalysts supported on zeolites and their applications in various organic transformations.

  20. 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.

  1. Enantioselective synthesis of chiral isotopomers of 1-alkanols by a ZACA-Cu-catalyzed cross-coupling protocol.

    PubMed

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

    2014-12-01

    Chiral compounds arising from the replacement of hydrogen atoms by deuterium are very important in organic chemistry and biochemistry. Some of these chiral compounds have a non-measurable specific rotation, owing to very small differences between the isotopomeric groups, and exhibit cryptochirality. This particular class of compounds is difficult to synthesize and characterize. Herein, we present a catalytic and highly enantioselective conversion of terminal alkenes to various β and more remote chiral isotopomers of 1-alkanols, with ≥99 % enantiomeric excess (ee), by the Zr-catalyzed asymmetric carboalumination of alkenes (ZACA) and Cu-catalyzed cross-coupling reactions. ZACA-in situ iodinolysis of allyl alcohol and ZACA-in situ oxidation of TBS-protected ω-alkene-1-ols protocols were applied to the synthesis of both (R)- and (S)-difunctional intermediates with 80-90 % ee. These intermediates were readily purified to provide enantiomerically pure (≥99 % ee) compounds by lipase-catalyzed acetylation. These functionally rich intermediates serve as very useful synthons for the construction of various chiral isotopomers of 1-alkanols in excellent enantiomeric purity (≥99 % ee) by introducing deuterium-labeled groups by Cu-catalyzed cross-coupling reactions without epimerization.

  2. Palladium-Catalyzed Arylation of Alkyl Sulfenate Anions.

    PubMed

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

    2015-11-04

    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.

  3. Functional Group Tolerant Nickel-Catalyzed Cross-Coupling Reaction for Enantioselective Construction of 30 Methyl-Bearing Stereocenters

    PubMed Central

    Wisniewska, Hanna M.; Swift, Elizabeth C.; Jarvo, Elizabeth R.

    2013-01-01

    The first Negishi nickel-catalyzed stereospecific cross-coupling reaction of secondary benzylic esters is reported. A series of traceless directing groups are evaluated for ability to promote cross-coupling with dimethylzinc. Esters with a chelating thioether derived from commercially-available 2-(methylthio)acetic acid are most effective. The products are formed in high yield and with excellent stereospecificity. A variety of functional groups are tolerated in the reaction including alkenes, alkynes, esters, amines, imides, and O-, S-, and N-heterocycles. The utility of this transformation is highlighted in the enantioselective synthesis of a retinoic acid receptor (RAR) agonist and a fatty acid amide hydrolase (FAAH) inhibitor. PMID:23751004

  4. Palladium-Catalyzed Synthesis of 9-Fluorenylidenes through Aryne Annulation

    PubMed Central

    Worlikar, Shilpa A.; Larock, Richard C.

    2009-01-01

    The palladium-catalyzed annulation of arynes by substituted ortho-halostyrenes produces substituted 9- fluorenylidenes in good yields. This methodology provides this important carbocyclic ring system in a single step, which involves the generation of two new carbon-carbon bonds, occurs under relatively mild reaction conditions and tolerates a variety of functional groups, including cyano, ester, aldehyde and ketone groups. PMID:19413328

  5. Palladium-catalyzed direct arylation of indoles with cyclohexanones.

    PubMed

    Chen, Shanping; Liao, Yunfeng; Zhao, Feng; Qi, Hongrui; Liu, Saiwen; Deng, Guo-Jun

    2014-03-21

    A novel palladium catalyzed approach to 3-arylindoles was developed from indoles and cyclohexanones. Various cyclohexanones acted as aryl sources via an alkylation and dehydrogenation sequence using molecular oxygen as the hydrogen acceptor. This method showed good regioselectivity and afforded 3-arylindoles as the sole products.

  6. Palladium-catalyzed stereocontrolled vinylation of azoles and phenothiazine.

    PubMed

    Lebedev, Artyom Y; Izmer, Vyatcheslav V; Kazyul'kin, Denis N; Beletskaya, Irina P; Voskoboynikov, Alexander Z

    2002-02-21

    [reaction: see text] Vinylation of various azoles (pyrrole, indole, carbazole, and their derivatives) and phenothiazine with vinyl bromides catalyzed by palladium-phosphine complexes results in the respective N-vinylazoles in 30-99% yields. This reaction with cis- and trans-beta-bromostyrenes is stereospecific giving the respective products with full retention of configuration.

  7. Palladium-catalyzed silylation of aryl chlorides with hexamethyldisilane.

    PubMed

    McNeill, Eric; Barder, Timothy E; Buchwald, Stephen L

    2007-09-13

    A method for the palladium-catalyzed silylation of aryl chlorides has been developed. The method affords desired product in good yield, is tolerant of a variety of functional groups, and provides access to a wide variety of aryltrimethylsilanes from commercially available aryl chlorides. Additionally, a one-pot procedure that converts aryl chlorides into aryl iodides has been developed.

  8. Palladium-catalyzed synthesis of functionalized tetraarylphosphonium salts.

    PubMed

    Marcoux, David; Charette, André B

    2008-01-18

    An efficient method to synthesize functionalized tetraarylphosphonium salts is described. This palladium-catalyzed coupling reaction between aryl iodides, bromides, or triflates and triphenylphosphine generates phosphonium salts in high yields. The coupling is compatible with a variety of functional groups such as alcohols, ketones, aldehydes, phenols, and amides.

  9. Palladium(II)-catalyzed direct alkenylation of nonaromatic enamides.

    PubMed

    Gigant, Nicolas; Gillaizeau, Isabelle

    2012-07-06

    A mild and efficient method for the direct alkenylation of nonaromatic enamides was achieved through a palladium(II)-catalyzed C-H functionalization. The reaction scope includes cyclic and acyclic enamides and a range of activated alkenes. This approach represents the first successful direct C(3)-functionalization of nonaromatic cyclic enamides.

  10. Palladium-catalyzed enantioselective 1,1-fluoroarylation of aminoalkenes.

    PubMed

    He, Ying; Yang, Zhenyu; Thornbury, Richard T; Toste, F Dean

    2015-09-30

    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.

  11. 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

  12. Palladium(III)-Catalyzed Fluorination of Arylboronic Acid Derivatives

    PubMed Central

    Tang, Pingping; Murphy, Jennifer M.; Ritter, Tobias

    2013-01-01

    A practical, palladium-catalyzed synthesis of aryl fluorides from arylboronic acid derivatives is presented. The reaction is operationally simple and amenable to multi-gram-scale synthesis. Evaluation of the reaction mechanism suggests a single-electron-transfer pathway, involving a Pd(III) intermediate that has been isolated and characterized. PMID:24040932

  13. Palladium(III)-catalyzed fluorination of arylboronic acid derivatives.

    PubMed

    Mazzotti, Anthony R; Campbell, Michael G; Tang, Pingping; Murphy, Jennifer M; Ritter, Tobias

    2013-09-25

    A practical, palladium-catalyzed synthesis of aryl fluorides from arylboronic acid derivatives is presented. The reaction is operationally simple and amenable to multigram-scale synthesis. Evaluation of the reaction mechanism suggests a single-electron-transfer pathway, involving a Pd(III) intermediate that has been isolated and characterized.

  14. Palladium catalyzed alkoxy- and aminocarbonylation of vinyl tosylates.

    PubMed

    Reeves, Diana C; Rodriguez, Sonia; Lee, Heewon; Haddad, Nizar; Krishnamurthy, Dhileepkumar; Senanayake, Chris H

    2011-05-06

    The palladium catalyzed alkoxycarbonylation and aminocarbonylation of vinyl tosylates are described. A variety of ketone and aldehyde derived vinyl tosylates may be carbonylated in the presence of primary, secondary, and tertiary alcohols, or primary and secondary amines, to provide the corresponding esters and amides in good yields. The alkoxycarbonylation was applied to a short synthesis of isoguvacine.

  15. Palladium-catalyzed selective acyloxylation using sodium perborate as oxidant.

    PubMed

    Pilarski, Lukasz T; Janson, Pär G; Szabó, Kálmán J

    2011-03-04

    Sodium perborate (SPB), a principal component of washing powders, was employed as an inexpensive and eco-friendly oxidant in the palladium-catalyzed C-H acyloxylation of alkenes in excellent regio- and stereochemistry. The reactions used anhydrides as acyloxy sources. The method applies to both terminal and internal alkenes, and even benzylic C-H oxidation.

  16. 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

    2015-08-07

    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.

  17. Simple, Efficient Protocols for the Pd-Catalyzed Cross-Coupling Reaction of Aryl Chlorides and Dimethylamine

    PubMed Central

    Lee, Brian K.; Biscoe, Mark R.; Buchwald, Stephen L.

    2011-01-01

    Simple and efficient procedures for the Pd-catalyzed cross-coupling reaction of aryl chlorides and dimethylamine are described. At room temperature with a strong base, t-BuXPhos is employed as the supporting ligand; at 110 °C with a weak base, XPhos is employed as the supporting ligand. In each of these cases, commercially available solutions constitute the source of the dimethylamine, and recently disclosed precatalysts constitute the source of the ligand and Pd. This work further expands the utility of these precatalysts in reactions that benefit from an easily activated source of L1Pd(0). PMID:21818164

  18. 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

  19. 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.

  20. Rh(I)-Catalyzed Intermolecular Hydroacylation: Enantioselective Cross-Coupling of Aldehydes and Ketoamides

    PubMed Central

    2015-01-01

    Under Rh(I) catalysis, α-ketoamides undergo intermolecular hydroacylation with aliphatic aldehydes. A newly designed Josiphos ligand enables access to α-acyloxyamides with high atom-economy and enantioselectivity. On the basis of mechanistic and kinetic studies, we propose a pathway in which rhodium plays a dual role in activating the aldehyde for cross-coupling. A stereochemical model is provided to rationalize the sense of enantioinduction observed. PMID:24937681

  1. 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

  2. Synthesis of vinyl sulfides by copper-catalyzed decarboxylative C-S cross-coupling.

    PubMed

    Ranjit, Sadananda; Duan, Zhongyu; Zhang, Pengfei; Liu, Xiaogang

    2010-09-17

    A novel method for the synthesis of vinyl sulfides by the decarboxylative cross-coupling of arylpropiolic acids with thiols using copper(I) salts as catalysts has been developed. In the presence of CuI and Cs(2)CO(3), a variety of thiols reacted with arylpropiolic acids to afford the corresponding vinyl sulfides in good to excellent yields with high stereoselectivity for Z-isomers.

  3. Palladium-Catalyzed Carbonylation of sec- and tert-Alcohols.

    PubMed

    Dong, Kaiwu; Sang, Rui; Liu, Jie; Razzaq, Rauf; Franke, Robert; Jackstell, Ralf; Beller, Matthias

    2017-05-22

    A general palladium-catalyzed synthesis of linear esters directly from sec- and tert-alcohols is described. Compared to the classic Koch-Haaf reaction, which leads to branched products, this new transformation gives the corresponding linear esters in high yields and selectivity. Key for this protocol is the use of an advanced palladium catalyst system with L2 (py(t) bpx) as the ligand. A variety of aliphatic and benzylic alcohols can be directly used and the catalyst efficiency for the benchmark reaction is outstanding (turnover number up to 89 000). © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Palladium-Catalyzed Construction of Heteroatom-Containing π-Conjugated Systems by Intramolecular Oxidative C-H/C-H Coupling Reaction.

    PubMed

    Saito, Kenta; Chikkade, Prasanna Kumara; Kanai, Motomu; Kuninobu, Yoichiro

    2015-06-01

    Synthesis of heteroatom-containing ladder-type π-conjugated molecules was successfully achieved via a palladium-catalyzed intramolecular oxidative C-H/C-H cross-coupling reaction. This reaction provides a variety of π-conjugated molecules bearing heteroatoms, such as nitrogen, oxygen, phosphorus, and sulfur atoms, and a carbonyl group. The π-conjugated molecules were synthesized efficiently, even in gram scale, and larger π-conjugated molecules were also obtained by a double C-H/C-H cross-coupling reaction and successive oxidative cycloaromatization.

  5. New Palladium-Catalyzed Approaches to Heterocycles and Carbocycles

    SciTech Connect

    Huang, Qinhua

    2004-12-19

    The tert-butylimines of o-(1-alkynyl)benzaldehydes and analogous pyridinecarbaldehydes have been cyclized under very mild reaction conditions in the presence of I2, ICl, PhSeCl, PhSCl and p-O2NC6H4SCl 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

  6. Palladium-Catalyzed, Enantioselective Heine Reaction

    PubMed Central

    2016-01-01

    Aziridines are important synthetic intermediates for the generation of nitrogen-containing molecules. N-Acylaziridines undergo rearrangement by ring expansion to produce oxazolines, a process known as the Heine reaction. The first catalytic, enantioselective Heine reaction is reported for meso-N-acylaziridines where a palladium(II)–diphosphine complex is employed. The highly enantioenriched oxazoline products are valuable organic synthons and potential ligands for transition-metal catalysis. PMID:27398262

  7. Palladium-Catalyzed, Enantioselective Heine Reaction.

    PubMed

    Punk, Molly; Merkley, Charlotte; Kennedy, Katlyn; Morgan, Jeremy B

    2016-07-01

    Aziridines are important synthetic intermediates for the generation of nitrogen-containing molecules. N-Acylaziridines undergo rearrangement by ring expansion to produce oxazolines, a process known as the Heine reaction. The first catalytic, enantioselective Heine reaction is reported for meso-N-acylaziridines where a palladium(II)-diphosphine complex is employed. The highly enantioenriched oxazoline products are valuable organic synthons and potential ligands for transition-metal catalysis.

  8. Palladium-catalyzed asymmetric quaternary stereocenter formation.

    PubMed

    Gottumukkala, Aditya L; Matcha, Kiran; Lutz, Martin; de Vries, Johannes G; Minnaard, Adriaan J

    2012-05-29

    An efficient palladium catalyst is presented for the formation of benzylic quaternary stereocenters by conjugate addition of arylboronic acids to a variety of β,β-disubstituted carbocyclic, heterocyclic, and acyclic enones. The catalyst is readily prepared from PdCl(2), PhBOX, and AgSbF(6), and provides products in up to 99% enantiomeric excess, with good yields. Based on this strategy, (-)-α-cuparenone has been prepared in only two steps. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. A New Class of Easily Activated Palladium Precatalysts for Facile C–N Cross-Coupling Reactions and Low Temperature Oxidative Addition of Aryl Chlorides

    PubMed Central

    Biscoe, Mark R.; Fors, Brett P.; Buchwald, Stephen L.

    2008-01-01

    A new class of one-component Pd precatalysts bearing biarylphosphine ligands is described. These precatalysts are air- and thermally-stable, are easily activated under normal reaction conditions at or below room temperature, and ensure the formation of the highly active mono-ligated Pd(0) complex necessary for oxidative addition. The use of these precatalysts as a convenient source of LPd(0) in C-N cross-coupling reactions is explored. The reactivity that is demonstrated in this study is unprecedented in palladium chemistry. PMID:18447360

  10. 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

  11. Asymmetric Palladium-Catalyzed Directed Intermolecular Fluoroarylation of Styrenes

    PubMed Central

    2015-01-01

    A mild catalytic asymmetric direct fluoro-arylation of styrenes has been developed. The palladium-catalyzed three-component coupling of Selectfluor, a styrene and a boronic acid, provides chiral monofluorinated compounds in good yield and in high enantiomeric excess. A mechanism proceeding through a Pd(IV)-fluoride intermediate is proposed for the transformation and synthesis of an sp3 C–F bond. PMID:24617344

  12. Rhodium(III)-catalyzed cross-coupling of alkenylboronic acids and N-pivaloyloxylamides.

    PubMed

    Feng, Chao; Loh, Teck-Peng

    2014-07-03

    Rh(III)-catalyzed umpolung amidation of alkenylboronic acids for the synthesis of enamides is reported. This reaction proceeds readily at room temperature and displays an extremely wide spectrum of functional group tolerance. With cooperation of hydroboration, it enables the formal anti-Markovnikov hydroamidation of terminal alkynes, stereospecifically affording the trans-enamides in excellent yields.

  13. Synthesis of alkenyl sulfides through the iron-catalyzed cross-coupling reaction of vinyl halides with thiols.

    PubMed

    Lin, Yun-Yung; Wang, Yu-Jen; Lin, Che-Hung; Cheng, Jun-Hao; Lee, Chin-Fa

    2012-07-20

    We report here the iron-catalyzed cross-coupling reaction of alkyl vinyl halides with thiols. While many works are devoted to the coupling of thiols with alkyl vinyl iodides, interestingly, the known S-vinylation of vinyl bromides and chlorides is limited to 1-(2-bromovinyl)benzene and 1-(2-chlorovinyl)benzene. Investigation on the coupling reaction of challenging alkyl vinyl bromides and chlorides with thiols is rare. Since the coupling of 1-(2-bromovinyl)benzene and 1-(2-chlorovinyl)benzene with thiols can be performed in the absence of any catalyst, here we focus on the coupling of thiols with alkyl vinyl halides. This system is generally reactive for alkyl vinyl iodides and bromides to provide the products in good yields. 1-(Chloromethylidene)-4-tert-butyl-cyclohexane was also coupled with thiols, giving the targets in moderate yields.

  14. Ni(I) Catalyzes the Regioselective Cross-Coupling of Alkylzinc Halides and Propargyl Bromides to Allenes.

    PubMed

    Soler-Yanes, Rita; Arribas-Álvarez, Iván; Guisán-Ceinos, Manuel; Buñuel, Elena; Cárdenas, Diego J

    2017-01-31

    We describe the unprecedented formation of allenes by Ni-catalyzed cross-coupling of propargyl bromides with alkylzinc halides. The reaction regioselectivity is complementary to the previously reported formation of propargyl-coupled compounds. Experiments support the formation of Ni(I) complexes as the active species and the participation of radical intermediates. Kinetic studies showed that the reaction is first order with respect to the electrophile, zero-order with respect to the nucleophile (fast transmetalation), and one-half order with respect to the metal catalyst. Mechanistic studies support a bimetallic Ni(I) -based pathway that involves fast homolytic cleavage of the C-Br bond by an alkyl-Ni(I) complex, followed by radical coordination to Ni(I) that determines the observed regioselectivity.

  15. 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.

  16. Aluminum-Catalyzed Cross-Coupling of Silylalkynes with Aliphatic C-F Bonds.

    PubMed

    Jaiswal, Amit K; Goh, Kelvin K K; Sung, Simon; Young, Rowan D

    2017-04-07

    We report the generation of aliphatic and benzylic acetylenes via reaction of primary, secondary, and tertiary aliphatic fluorides with various trimethylsilyl acetylides. These reactions are catalyzed by Al and B Lewis acids, most effectively by the extremely fluorophilic tris(pentafluorophenyl)alane, representing the first example of catalytic incorporation of alkynes into aliphatic C-F positions. The fluorophilicity of the catalysts gives rise to fluorine selectivity over other halogens, allowing orthogonal reactivity pathways.

  17. Palladium(ii)-Acetylacetonato Complexes with Mesoionic Carbenes: Synthesis, Structures and Their Application in the Suzuki-Miyaura Cross Coupling Reaction.

    PubMed

    Hettmanczyk, Lara; Schmid, Bianca; Hohloch, Stephan; Sarkar, Biprajit

    2016-11-17

    A series of novel palladium(ii) acetylacetonato complexes bearing mesoionic carbenes (MICs) have been synthesized and characterized. The synthesis of the complexes of type (MIC)Pd(acac)I (MIC = 1-mesityl-3-methyl-4-phenyl-1,2,3-triazol-5-ylidene (1), 1,4-(2,4,6-methyl)-phenyl-3-methyl-1,2,3-triazol-5-ylidene (2), 1,4-(2,6-diisopropyl)-phenyl-3-methyl-1,2,3-triazol-5-ylidene (3); acac = acetylacetonato) via direct metalation starting from the corresponding triazolium iodides and palladium(ii) acetylacetonate is described herein. All complexes were characterized by ¹H- and (13)C-NMR spectroscopy and high resolution mass spectrometry. Additionally, two of the complexes were characterized by single crystal X-ray crystallography confirming a square-planar coordination geometry of the palladium(ii) center. A delocalized bonding situation was observed within the triazolylidene rings as well as for the acac ligand respectively. Complex 2 was found to be an efficient pre-catalyst for the Suzuki-Miyaura cross coupling reaction between aryl-bromides or -chlorides with phenylboronic acid.

  18. Palladium-catalyzed carbonylation of o-iodoanilines for synthesis of isatoic anhydrides.

    PubMed

    Gao, Sha; Chen, Ming; Zhao, Mi-Na; Du, Wei; Ren, Zhi-Hui; Wang, Yao-Yu; Guan, Zheng-Hui

    2014-05-02

    A novel palladium-catalyzed oxidative double carbonylation of o-iodoanilines for the synthesis of isatoic anhydrides has been developed. The reaction employs readily available o-iodoanilines as the starting materials and proceeds under mild conditions. For extension, palladium-catalyzed oxidative carbonylation of anthranilic acids was developed for the synthesis of substituted isatoic anhydrides in high to excellent yields.

  19. Pyrrolodiazines. 6. Palladium-catalyzed arylation, heteroarylation, and amination of 3,4-dihydropyrrolo[1,2-a]pyrazines.

    PubMed

    Castellote, Isabel; Vaquero, Juan J; Fernández-Gadea, Javier; Alvarez-Builla, Julio

    2004-12-10

    The palladium-catalyzed Suzuki cross-coupling reaction of arylboronic acids and 6-bromo- and 6,8-dibromo-3,4-dihydropyrrolo[1,2-a]pyrazines afforded 6-substituted and 6,8-disubstituted 3,4-dihydropyrrolo[1,2-a]pyrazines in good yields. Stille and Negishi coupling reactions have been used to prepare 6-heteroaryl-substituted derivatives in moderate yields by employing heteroaryl halides and 6-metalated 3,4-dihydropyrrolo[1,2-a]pyrazines as reaction partners. A variety of cyclic secondary amines have also been incorporated at position C-6 of 6-bromo-1-phenyl-3,4-dihydropyrrolo[1,2-a]pyrazine in the presence of the palladium catalyst Pd(2)(dba)(3) in conjunction with BINAP as ligand. This amination reaction is one of the few reported examples of such a palladium-catalyzed transformation on a pyrrole ring, although the reaction could not be extended to less nucleophilic amines.

  20. Synthesis of Dihydrobenzofurans via Palladium-Catalyzed Heteroannulations

    SciTech Connect

    Rozhkov, Roman Vladimirovich

    2004-01-01

    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 β-hydrogen in the vinylic halide results in β-hydride elimination giving the corresponding alkyne. The presence of a bulky group in the α-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. Palladium-Catalyzed Enantioselective Decarboxylative Allylic Alkylation of Cyclopentanones.

    PubMed

    Craig, Robert A; Loskot, Steven A; Mohr, Justin T; Behenna, Douglas C; Harned, Andrew M; Stoltz, Brian M

    2015-11-06

    The first general method for the enantioselective construction of all-carbon quaternary centers on cyclopentanones by enantioselective palladium-catalyzed decarboxylative allylic alkylation is described. Employing the electronically modified (S)-(p-CF3)3-t-BuPHOX ligand, α-quaternary cyclopentanones were isolated in yields up to >99% with ee's up to 94%. Additionally, in order to facilitate large-scale application of this method, a low catalyst loading protocol was employed, using as little as 0.15 mol % Pd, furnishing the product without any loss in ee.

  2. nBu4NI-catalyzed oxidative cross-coupling of carbon dioxide, amines, and aryl ketones: access to O-β-oxoalkyl carbamates.

    PubMed

    Peng, Youbin; Liu, Juan; Qi, Chaorong; Yuan, Gaoqing; Li, Jiawei; Jiang, Huanfeng

    2017-02-28

    The first nBu4NI-catalyzed oxidative cross-coupling reaction of carbon dioxide, amines and arylketones has been successfully developed by using TBHP as the oxidant, providing an efficient, atom-economical and metal-free strategy for the synthesis of a range of O-β-oxoalkyl carbamates.

  3. 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.

  4. A Palladium Catalyst System for the Efficient Cross-Coupling Reaction of Aryl Bromides and Chlorides with Phenylboronic Acid: Synthesis and Biological Activity Evaluation.

    PubMed

    Lamia, Boubakri; Chakchouk-Mtibaa, Ahlem; Hallouma, Bilel; Mansour, Lamjed; Mellouli, Lotfi; Özdemir, Ismail; Yaşar, Sedat; Hamdi, Naceur

    2017-03-07

    New benzimidazolium salts 1a-c and their palladium bis-N-heterocyclic carbene complexes 2a-c and palladium PEPPSI-type complexes 3a-c were designed, synthesized and structurally characterized by NMR (1H and 13C), IR, DART-TOF mass spectrometry and elemental analysis. Then these complexes 2-3 were employed in the Suzuki-Miyaura cross-coupling reaction of substituted arenes with phenylboronic acid under mild conditions in toluene and DMF/H2O (1/1) to afford functionalized biaryl derivatives in good to excellent yields. The antibacterial activity of palladium bis-N-heterocyclic carbene complexes 2a-c and palladium PEPPSI-type complexes 3a-c was measured by disc diffusion method against Gram positive and Gram negative bacteria. Compounds 2a, 2c and 3a-c exhibited potential antibacterial activity against four bacterial species among the five used indicator cells. The product 2b inhibits the growth of the all five tested microorganisms. Moreover, the antioxidant activity determination of these complexes 2-3, using 2.2-diphenyl-1-picrylhydrazyl (DPPH) as a reagent, showed that compounds 2a-c and 3b possess DPPH antiradical activity. The higher antioxidant activity was obtained from the product 2b which has radical scavenging activity comparable to that of the two used positive controls (gallic acid "GA" and tutylatedhydroxytoluene "BHT"). Investigation of the anti-acetylcholinesterase activity of the studied complexes showed that compounds 2b, 3a, and 3b exhibited moderate activity at 100 μg/mL and product 2b is the most active.

  5. Combined Theoretical and Experimental Studies of Nickel-Catalyzed Cross-Coupling of Methoxyarenes with Arylboronic Esters via C-O Bond Cleavage.

    PubMed

    Schwarzer, Martin C; Konno, Ryosuke; Hojo, Takayuki; Ohtsuki, Akimichi; Nakamura, Keisuke; Yasutome, Ayaka; Takahashi, Hiroaki; Shimasaki, Toshiaki; Tobisu, Mamoru; Chatani, Naoto; Mori, Seiji

    2017-08-02

    Nickel(0)-catalyzed cross-coupling of methoxyarenes through C-O bond activation has been the subject of considerable research because of their favorable features compared with those of the cross-coupling of aryl halides, such as atom economy and efficiency. In 2008, we have reported nickel/PCy3-catalyzed cross-coupling of methoxyarenes with arylboronic esters in which the addition of a stoichiometric base such as CsF is essential for the reaction to proceed. Recently, we have also found that the scope of the substrate in the Suzuki-Miyaura-type cross-coupling of methoxyarenes can be greatly expanded by using 1,3-dicyclohexylimidazol-2-ylidene (ICy) as the ligand. Interestingly, a stoichiometric amount of external base is not required for the nickel/ICy-catalyzed cross-coupling. For the mechanism and origin of the effect of the external base to be elucidated, density functional theory calculations are conducted. In the nickel/PCy3-catalyzed reactions, the activation energy for the oxidative addition of the C(aryl)-OMe bond is too high to occur under the catalytic conditions. However, the oxidative addition process becomes energetically feasible when CsF and an arylboronic ester interact with a Ni(PCy3)2/methoxyarene fragment to form a quaternary complex. In the nickel/ICy-catalyzed reactions, the oxidative addition of the C(aryl)-OMe bond can proceed more easily without the aid of CsF because the nickel-ligand bonds are stronger and therefore stabilize the transition state. The subsequent transmetalation from an Ar-Ni-OMe intermediate is determined to proceed through a pathway with lower energies than those required for β-hydrogen elimination. The overall driving force of the reaction is the reductive elimination to form the carbon-carbon bond.

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

    PubMed

    Yamamoto, Tetsuya; Yamakawa, Tetsu

    2012-07-06

    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.

  7. Palladium(II)-Catalyzed Enantioselective Reactions Using COP Catalysts.

    PubMed

    Cannon, Jeffrey S; Overman, Larry E

    2016-10-18

    Allylic amides, amines, and esters are key synthetic building blocks. Their enantioselective syntheses under mild conditions is a continuing pursuit of organic synthesis methods development. One opportunity for the synthesis of these building blocks is by functionalization of prochiral double bonds using palladium(II) catalysis. In these reactions, nucleopalladation mediated by a chiral palladium(II) catalyst generates a new heteroatom-substituted chiral center. However, reactions where nucleopalladation occurs with antarafacial stereoselectivity are difficult to render enantioselective because of the challenge of transferring chiral ligand information across the square-planar palladium complex to the incoming nucleophile. In this Account, we describe the development and use of enantiopure palladium(II) catalysts of the COP (chiral cobalt oxazoline palladacyclic) family for the synthesis of enantioenriched products from starting materials derived from prochiral allylic alcohols. We begin with initial studies aimed at rendering catalyzed [3,3]-sigmatropic rearrangements of allylic imidates enantioselective, which ultimately led to the identification of the significant utility of the COP family of Pd(II) catalysts. The first use of an enantioselective COP catalyst was reported by Richards' and our laboratories in 2003 for the enantioselective rearrangement of allylic N-arylimidates. Shortly thereafter, we discovered that the chloride-bridged COP dimer, [COP-Cl]2, was an excellent enantioselective catalyst for the rearrangement of (E)-allylic trichloroacetimidates to enantioenriched allylic trichloroacetamides, this conversion being the most widely used of the allylic imidate rearrangements. We then turn to discuss SN2' reactions catalyzed by the acetate-bridged COP dimer, [COP-OAc]2, which proceed by a unique mechanism to provide branched allylic esters and allylic phenyl ethers in high enantioselectivity. Furthermore, because of the unique nucleopalladation

  8. 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

    2015-09-09

    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.

  9. Crystalline hybrid solid materials of palladium and decamethylcucurbit[5]uril as recoverable precatalysts for Heck cross-coupling reactions.

    PubMed

    Li, Hongfang; Lü, Jian; Lin, Jingxiang; Huang, Yuanbiao; Cao, Minna; Cao, Rong

    2013-11-11

    A series of MPdMe10 CB[5] (M=Li, Na, K, Rb, and Cs; Me10 CB[5]=decamethylcucurbit[5]uril) hybrid solid materials have been successfully synthesized for the first time through a simple diffusion method. These as-prepared hybrid solids have been applied as phosphine-free precatalysts for Heck cross-coupling reactions with excellent catalytic performance and good recyclability. In the processes of the catalytic reactions, the activated Pd(II) species were released from the crystalline hybrid precatalysts and transformed into catalytically active Pd nanoparticles, which have been demonstrated as key to carry on the catalytic reactions for the recoverable precatalysts MPdMe10 CB[5] (M=K, Rb, and Cs). It has also been rationalized that the introduction of different alkali metals afforded crystalline hybrid precatalysts with different crystal structures, which are responsible for their diversified stability and reusability presented in Heck reactions.

  10. 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

  11. A general, efficient, and functional-group-tolerant catalyst system for the palladium-catalyzed thioetherification of aryl bromides and iodides.

    PubMed

    Fernández-Rodríguez, Manuel A; Hartwig, John F

    2009-02-20

    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 2 or 3 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.

  12. Unexpected formation of aryl ketones by palladium-catalyzed coupling of aryl bromides with vinylic acetates.

    PubMed

    Jean, Mickaël; Renault, Jacques; Uriac, Philippe; Capet, Marc; van de Weghe, Pierre

    2007-08-30

    A palladium-catalyzed coupling reaction of aryl bromides with vinylic acetates in the presence of tributyltin methoxide has been described. Unexpected formation of aryl ketones was obtained. Preliminary mechanistic studies indicated that the reaction proceeded by the addition of the aryl moiety in the coordination sphere of palladium to a ketene.

  13. Successive copper(I)-catalyzed cross-couplings in one pot: a novel and efficient starting point for synthesis of carbapenems.

    PubMed

    Jiang, Biao; Tian, Hua; Huang, Zuo-Gang; Xu, Min

    2008-07-03

    An efficient approach for synthesizing a series of 2-sulfide carbapenems has been developed using two successive Cu(I)-catalyzed cross-couplings in a single pot. The method involves highly selective intramolecular coupling of lactam and dihaloalkene using 2,2'-bipyridine as a ligand, followed by intermolecular C-S formation in the presence of another ligand (1,10-phenanthroline, PPh 3) and mercaptan.

  14. Nickel-catalyzed Suzuki-Miyaura type cross-coupling reactions of (2,2-difluorovinyl)benzene derivatives with arylboronic acids.

    PubMed

    Xiong, Yang; Huang, Tao; Ji, Xinfei; Wu, Jingjing; Cao, Song

    2015-07-21

    An unprecedented highly stereoselective example of nickel-catalyzed Suzuki-Miyaura type cross-coupling reactions of (2,2-difluorovinyl)benzene derivatives with arylboronic acids was developed. The reaction proceeded efficiently in the presence of 5 mol% NiCl2(PCy3)2 and K3PO4, affording the Z-fluorostyrene derivatives in good to high yields with excellent regioselectivity.

  15. Sterically Controlled Cu-Catalyzed or Transition-Metal-Free Cross-Coupling of gem-Difluoroalkenes with Tertiary, Secondary, and Primary Alkyl Grignard Reagents.

    PubMed

    Dai, Wenpeng; Shi, Hongyan; Zhao, Xianghu; Cao, Song

    2016-09-02

    A robust copper-catalyzed or transition-metal-free cross-coupling of gem-difluoroalkenes with tertiary, secondary, and primary alkyl Grignard reagents has been developed. Remarkably, the tertiary and secondary alkylation of gem-difluoroalkenes proceeded very smoothly in the presence of 25 mol % of CuCN or under transition-metal-free conditions, affording the tertiary and secondary alkyl-substituted fluoroalkenes in good to excellent yields with excellent Z stereoselectivity.

  16. Nickel-catalyzed cross-coupling reaction of aryl fluorides and chlorides with grignard reagents under nickel/magnesium bimetallic cooperation.

    PubMed

    Yoshikai, Naohiko; Mashima, Hiroko; Nakamura, Eiichi

    2005-12-28

    Nickel-catalyzed cross-coupling of Grignard reagents with aryl (poly)fluorides or (poly)chlorides can be achieved efficiently in the presence of a new triarylphosphine ligand bearing a nearby hydroxy group. The high reactivity and the unique chemoselectivity (ArF > ArOTf > ArSR) of the catalysis have been attributed to synergy of nickel and magnesium atoms preorganized on the ligand, as has been surmised on the basis of theoretical modeling of the reaction mechanism.

  17. Palladium-catalyzed allylic amination: a powerful tool for the enantioselective synthesis of acyclic nucleoside phosphonates.

    PubMed

    Azzouz, Mariam; Soriano, Sébastien; Escudero-Casao, Margarita; Matheu, M Isabel; Castillón, Sergio; Díaz, Yolanda

    2017-08-30

    Acyclic nucleoside phosphonates have been prepared in a straightforward manner and in high yields by an enantioselective palladium-catalyzed allylic substitution involving nucleic bases as nucleophiles followed by cross-metathesis reaction with diethyl allylphosphonate.

  18. 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...

  19. A novel palladium-catalyzed hydroalkoxylation of alkenes with a migration of double bond.

    PubMed

    Tan, Jiajing; Zhang, Zuhui; Wang, Zhiyong

    2008-04-21

    A novel palladium-catalyzed addition of alcohols to olefins was developed, in which a migration of double bond was involved. By this new method, a variety of allylic ethers were prepared with moderate to high yields under mild conditions.

  20. 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...

  1. N-heterocyclic carbene-assisted, bis(phosphine)nickel-catalyzed cross-couplings of diarylborinic acids with aryl chlorides, tosylates, and sulfamates.

    PubMed

    Ke, Haihua; Chen, Xiaofeng; Zou, Gang

    2014-08-01

    Efficient bis(phosphine)nickel-catalyzed cross-couplings of diarylborinic acids with aryl chlorides, tosylates, and sulfamates have been effected with an assistance of N-heterocyclic carbene (NHC) generated in situ from N,N'-dialkylimidazoliums, e.g., N-butyl-N'-methylimidazolium bromide ([Bmim]Br), in toluene using K3PO4·3H2O as base. In contrast to bis(NHC)nickel-catalyzed conventional Suzuki coupling of arylboronic acids, mono(NHC)bis(phosphine)nickel species generated in situ from Ni(PPh3)2Cl2/[Bmim]Br displayed high catalytic activities in the cross-couplings of diarylborinic acids. The structural influences from diarylborinic acids were found to be rather small, while electronic factors from aryl chlorides, tosylates, and sulfamates affected the couplings remarkably. The couplings of electronically activated aryl chlorides, tosylates, and sulfamates could be efficiently effected with 1.5 mol % NiCl2(PPh3)2/[Bmim]Br as catalyst precursor to give the biaryl products in excellent yields, while 3-5 mol % loadings had to be used for the couplings of non- and deactivated ones. A small ortho-substitutent on the aromatic ring of aryl chlorides, tosylates, and sulfamates was tolerable. Applicability of the nickel-catalyzed cross-couplings in practical synthesis of fine chemicals has been demonstrated in process development for a third-generation topical retinoid, Adapalene.

  2. Intermolecular Palladium-Catalyzed Oxidative Fluorocarbonylation of Unactivated Alkenes: Efficient Access to β-Fluorocarboxylic Esters.

    PubMed

    Qi, Xiaoxu; Yu, Feng; Chen, Pinhong; Liu, Guosheng

    2017-10-02

    A novel palladium-catalyzed intermolecular oxidative fluorocarbonylation of alkenes has been developed, in which employment of a cooperative process with electrophilic ArIF2 -meidated alkenes activation and palladium-catalyzed carbonylation is crucial for the successful catalytic transformation. The current transformation presents the first convenient method to generate β-fluorinated carboxylic acid derivatives under mild reaction conditions from simple alkenes with excellent regioselectivity. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

    PubMed

    Yu, Hui; Zhang, Guoying; Huang, Hanmin

    2015-09-07

    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.

  4. Stereoselective synthesis of 2,5-disubstituted morpholines using a palladium-catalyzed hydroamination reaction.

    PubMed

    McGhee, Alicia; Cochran, Brian M; Stenmark, Torrey A; Michael, Forrest E

    2013-08-04

    A palladium-catalyzed hydroamination reaction is the key step in a stereoselective synthesis of 2,5-disubstituted and 2,3,5-trisubsituted morpholines from carbamate-protected aziridines. Aziridines are selectively attacked at the more substituted position by unsaturated alcohol nucleophiles using Lewis acid catalysts. Palladium-catalyzed hydroamination of the resulting aminoalkenes gives morpholines as a single diastereomer in excellent yield.

  5. A highly efficient and aerobic protocol for the synthesis of N-heteroaryl substituted 9-arylcarbazolyl derivatives via a palladium-catalyzed ligand-free Suzuki reaction.

    PubMed

    Rao, Xiaofeng; Liu, Chun; Qiu, Jieshan; Jin, Zilin

    2012-10-21

    A palladium-catalyzed aerobic and ligand-free Suzuki reaction in aqueous ethanol has been developed for the synthesis of N-heteroaryl substituted 9-arylcarbazolyl derivatives. A number of N-heteroaryl halides, namely 2-halogenated pyridines, 2-bromoquinoline, 5-bromopyrimidine and 2-chloropyrazine, were coupled with 4-(9H-carbazol-9-yl)phenylboronic acid (CPBA) or 9-phenyl-9H-carbazol-3-ylboronic acid (PCBA) efficiently to afford good to excellent yields in a short reaction time. Moreover, the catalytic system of Pd(OAc)(2)-EtOH/H(2)O-K(2)CO(3) was successfully extended to the cross-couplings of N-heteroaryl halides with various arylboronic acids. The results demonstrated that the cross-coupling reaction in the present protocol was promoted by oxygen.

  6. 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.

  7. Stabilization of Two Radicals with One Metal: A Stepwise Coupling Model for Copper-Catalyzed Radical–Radical Cross-Coupling

    NASA Astrophysics Data System (ADS)

    Qi, Xiaotian; Zhu, Lei; Bai, Ruopeng; Lan, Yu

    2017-03-01

    Transition metal-catalyzed radical–radical cross-coupling reactions provide innovative methods for C–C and C–heteroatom bond construction. A theoretical study was performed to reveal the mechanism and selectivity of the copper-catalyzed C–N radical–radical cross-coupling reaction. The concerted coupling pathway, in which a C–N bond is formed through the direct nucleophilic addition of a carbon radical to the nitrogen atom of the Cu(II)–N species, is demonstrated to be kinetically unfavorable. The stepwise coupling pathway, which involves the combination of a carbon radical with a Cu(II)–N species before C–N bond formation, is shown to be probable. Both the Mulliken atomic spin density distribution and frontier molecular orbital analysis on the Cu(II)–N intermediate show that the Cu site is more reactive than that of N; thus, the carbon radical preferentially react with the metal center. The chemoselectivity of the cross-coupling is also explained by the differences in electron compatibility of the carbon radical, the nitrogen radical and the Cu(II)–N intermediate. The higher activation free energy for N–N radical–radical homo-coupling is attributed to the mismatch of Cu(II)–N species with the nitrogen radical because the electrophilicity for both is strong.

  8. Stabilization of Two Radicals with One Metal: A Stepwise Coupling Model for Copper-Catalyzed Radical–Radical Cross-Coupling

    PubMed Central

    Qi, Xiaotian; Zhu, Lei; Bai, Ruopeng; Lan, Yu

    2017-01-01

    Transition metal-catalyzed radical–radical cross-coupling reactions provide innovative methods for C–C and C–heteroatom bond construction. A theoretical study was performed to reveal the mechanism and selectivity of the copper-catalyzed C–N radical–radical cross-coupling reaction. The concerted coupling pathway, in which a C–N bond is formed through the direct nucleophilic addition of a carbon radical to the nitrogen atom of the Cu(II)–N species, is demonstrated to be kinetically unfavorable. The stepwise coupling pathway, which involves the combination of a carbon radical with a Cu(II)–N species before C–N bond formation, is shown to be probable. Both the Mulliken atomic spin density distribution and frontier molecular orbital analysis on the Cu(II)–N intermediate show that the Cu site is more reactive than that of N; thus, the carbon radical preferentially react with the metal center. The chemoselectivity of the cross-coupling is also explained by the differences in electron compatibility of the carbon radical, the nitrogen radical and the Cu(II)–N intermediate. The higher activation free energy for N–N radical–radical homo-coupling is attributed to the mismatch of Cu(II)–N species with the nitrogen radical because the electrophilicity for both is strong. PMID:28272407

  9. 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 Central

    Yoo, Kyung Soo; Yoon, Cheol Hwan; Jung, Kyung Woon

    2008-01-01

    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. PMID:17165795

  10. A novel 4-aminoantipyrine-Pd(II) complex catalyzes Suzuki-Miyaura cross-coupling reactions of aryl halides.

    PubMed

    Contreras-Celedón, Claudia Araceli; Mendoza-Rayo, Darío; Rincón-Medina, José A; Chacón-García, Luis

    2014-01-01

    A simple and efficient catalytic system based on a Pd complex of 4-aminoantipyrine, 4-AAP-Pd(II), was found to be highly active for Suzuki-Miyaura cross-coupling of aryl iodides and bromides with phenylboronic acids under mild reaction conditions. Good to excellent product yields from the cross-coupling reaction can be achieved when the reaction is carried out in ethanol, in the open air, using low loading of 4-AAP-Pd(II) as a precatalyst, and in the presence of aqueous K2CO3 as the base. A variety of functional groups are tolerated.

  11. NHC Nickel-Catalyzed Suzuki-Miyaura Cross-Coupling Reactions of Aryl Boronate Esters with Perfluorobenzenes.

    PubMed

    Zhou, Jing; Berthel, Johannes H J; Kuntze-Fechner, Maximilian W; Friedrich, Alexandra; Marder, Todd B; Radius, Udo

    2016-07-01

    An efficient Suzuki-Miyaura cross-coupling reaction of perfluorinated arenes with aryl boronate esters using NHC nickel complexes as catalysts is described. The efficiencies of different boronate esters (p-tolyl-Beg, p-tolyl-Bneop, p-tolyl-Bpin, p-tolyl-Bcat) and the corresponding boronic acid (p-tolyl-B(OH)2) in this type of cross-coupling reaction were evaluated (eg, ethyleneglycolato; neop, neopentylglycolato; pin, pinacolato; cat, catecholato). Aryl-Beg was shown to be the most reactive boronate ester among those studied. The use of CsF as an additive is essential for an efficient reaction of hexafluorobenzene with aryl neopentylglycolboronates.

  12. A novel 4-aminoantipyrine-Pd(II) complex catalyzes Suzuki–Miyaura cross-coupling reactions of aryl halides

    PubMed Central

    Mendoza-Rayo, Darío; Rincón-Medina, José A; Chacón-García, Luis

    2014-01-01

    Summary A simple and efficient catalytic system based on a Pd complex of 4-aminoantipyrine, 4-AAP–Pd(II), was found to be highly active for Suzuki–Miyaura cross-coupling of aryl iodides and bromides with phenylboronic acids under mild reaction conditions. Good to excellent product yields from the cross-coupling reaction can be achieved when the reaction is carried out in ethanol, in the open air, using low loading of 4-AAP–Pd(II) as a precatalyst, and in the presence of aqueous K2CO3 as the base. A variety of functional groups are tolerated. PMID:25550748

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

    PubMed

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

    2014-06-10

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

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

    PubMed Central

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

    2014-01-01

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

  15. Nickel-catalyzed cross-coupling reactions of benzylic zinc reagents with aromatic bromides, chlorides and tosylates.

    PubMed

    Schade, Matthias A; Metzger, Albrecht; Hug, Stephan; Knochel, Paul

    2008-07-14

    Benzylic zinc reagents prepared by direct insertion of zinc to benzylic chlorides in the presence of LiCl undergo smooth cross-coupling reactions with aromatic chlorides, bromides and tosylates using Ni(acac)(2) and PPh(3) as a catalyst system.

  16. Direct access to ketones from aldehydes via rhodium-catalyzed cross-coupling reaction with potassium trifluoro(organo)borates.

    PubMed

    Pucheault, Mathieu; Darses, Sylvain; Genet, Jean-Pierre

    2004-12-01

    A direct cross-coupling reaction of aromatic aldehydes with potassium trifluoro(organo)borates afforded ketones in high yields and under mild conditions in the presence of a rhodium catalyst and acetone. This new reaction, involving a formal aldehyde C-H bond activation, is believed to proceed via a Heck-type mechanism followed by hydride transfer to acetone.

  17. Cross coupling of magnesium diacetylenides with functional allylic and halide-containing compounds catalyzed by transition metal complexes

    SciTech Connect

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

    1986-08-20

    An efficient method has been developed for the synthesis of 1,4-enynes, conjugated acetylenes and aryl acetylenes by the cross coupling of magnesium diacetylenides with allyl ethers and esters, alkyl halides, allyl halides, aryl halides, allyl sulfides, and allylsulfones, using Ni and Pd complexes as the catalyst.

  18. Palladium-Catalyzed Decarboxylative Asymmetric Allylic Alkylation of Enol Carbonates

    PubMed Central

    Trost, Barry M.; Xu, Jiayi; Schmidt, Thomas

    2009-01-01

    Palladium-catalyzed decarboxylative asymmetric allylic alkylation (DAAA) of allyl enol carbonates as a highly chemo-, regio- and enantio-selective process for the synthesis of ketones bearing either a quaternary or a tertiary α-stereogenic center has been investigated in detail. Chiral ligand L4 was found to be optimal in the DAAA of a broad scope of cyclic and acyclic ketones including simple aliphatic ketones with more than one enolizable proton. The allyl moiety of the carbonates has been extended to a variety of cyclic or acyclic di-substituted allyl groups. Our mechanistic studies reveal that, similar to the direct allylation of lithium enolates, the DAAA reaction proceeds through an “outer sphere” SN2 type of attack on the π-allylpalladium complex by the enolate. An important difference between the DAAA reaction and the direct allylation of lithium enolates is that in the DAAA reaction, the nucleophile and the electrophile were generated simultaneously. Since the π-allylpalladium cation must serve as the counterion for the enolate, the enolate probably exists as a tight-ion-pair. This largely prevents the common side reactions of enolates associated with the equilibrium between different enolates. The much milder reaction conditions as well as the much broader substrate scope also represent the advantages of the DAAA reaction over the direct allylation of preformed metal enolates. PMID:19928805

  19. Mild palladium-catalyzed selective monoarylation of nitriles.

    PubMed

    Wu, Lingyun; Hartwig, John F

    2005-11-16

    Two new palladium-catalyzed procedures for the arylation of nitriles under less basic conditions than previously reported have been developed. The selective monoarylation of acetonitrile and primary nitriles has been achieved using alpha-silyl nitriles in the presence of ZnF2. This procedure is compatible with a variety of functional groups, including cyano, keto, nitro, and ester groups, on the aryl bromide. The arylation of secondary nitriles occurred in high yield by conducting reactions with zinc cyanoalkyl reagents. These reaction conditions tolerated base-sensitive functional groups, such as ketones and esters. The combination of these two methods, one with alpha-silyl nitriles and one with zinc cyanoalkyl reagents, provides a catalytic route to a variety of benzylic nitriles, which have not only biological significance but utility as synthetic intermediates. The utility of these new coupling reactions has been demonstrated by a synthesis of verapamil, a clinically used drug for the treatment of heart disease, by a three-step route from commercial materials that allows convenient variation of the aryl group.

  20. 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.

  1. Synthesis of Functionalized Pyrazoles via Vanadium-Catalyzed C-N Dehydrogenative Cross-Coupling and Fluorescence Switch-On Sensing of BSA Protein.

    PubMed

    Sar, Dinabandhu; Bag, Raghunath; Yashmeen, Afsana; Bag, Subhendu Sekhar; Punniyamurthy, Tharmalingam

    2015-11-06

    Vanadium-catalyzed C-N dehydrogenative cross-coupling of alkenyl hydrazones leading to functionalized pyrazoles is described in a 1:1 mixture of toluene/H2O using air as the terminal oxidant. Significant practical features include use of the commercial nontoxic VOSO4 as a recyclable catalyst, mild reaction conditions, scalability, and the broad substrate scope. Some of the product pyrazoles exhibit interesting photophysical properties. Fluorescence light-up sensing of BSA protein by one of the pyrazoles is also highlighted.

  2. 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…

  3. 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…

  4. 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.

  5. Palladium-catalyzed 1,4-difunctionalization of butadiene to form skipped polyenes.

    PubMed

    McCammant, Matthew S; Liao, Longyan; Sigman, Matthew S

    2013-03-20

    A palladium-catalyzed 1,4-addition across the commodity chemical 1,3-butadiene to afford skipped polyene products is reported. Through a palladium σ → π → σ allyl isomerization, two new carbon-carbon bonds are formed with high regioselectivity and trans stereoselectivity of the newly formed alkene. The utility of this method is highlighted by the successful synthesis of the ripostatin A skipped triene core.

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

    PubMed Central

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

    2012-01-01

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

  7. 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.

  8. Palladium-Catalyzed Fluorination of Cyclic Vinyl Triflates: Effect of TESCF3 as an Additive.

    PubMed

    Ye, Yuxuan; Takada, Takashi; Buchwald, Stephen L

    2016-12-12

    A method for the palladium-catalyzed fluorination of cyclic vinyl triflates has been developed. As with several previous palladium-catalyzed fluorination reactions using fluoride salts, controlling the regioselectivity presented a challenge in developing a practical synthetic procedure. The addition of triethyl(trifluoromethyl)silane (TESCF3 ) was found to effectively address this problem and resulted in drastically improved regioselectivities in this palladium-catalyzed fluorination reaction. This discovery, along with the use of a new biarylphosphine ligand, allowed for the development of an efficient and highly regioselective protocol for the fluorination of vinyl triflates. This method is compatible with a range of sensitive functional groups and provides access to five-, six-, and seven-membered cyclic vinyl fluorides.

  9. Synthesis of 1,5-benzothiazepine dipeptide mimetics via two CuI-catalyzed cross coupling reactions.

    PubMed

    Gan, Jiangang; Ma, Dawei

    2009-07-02

    CuI-catalyzed coupling of 4-methylphenyl bromide with amino acids gives N-aryl amino acids, which are converted into linear dipeptides via iodination and condensation with L-cysteine derived acyl chloride. Cyclization is achieved via a CuI/N,N-dimethylglycine catalyzed intramolecular coupling of aryl iodides with the liberated thiol to afford 1,5-benzothiazepine dipeptide mimetics.

  10. New approach to phosphinoalkynes based on Pd- and Ni-catalyzed cross-coupling of terminal alkynes with chlorophosphanes.

    PubMed

    Beletskaya, Irina P; Afanasiev, Vladimir V; Kazankova, Marina A; Efimova, Irina V

    2003-11-13

    [reaction: see text] The first example of direct phosphination of terminal alkynes with chlorophosphanes catalyzed by Ni or Pd complexes is described. Both aromatic and aliphatic terminal acetylenes undergo the coupling reaction to give corresponding coupling product in high yield.

  11. A Synthesis of Substituted α-Allenols via Iron-Catalyzed Cross-Coupling of Propargyl Carboxylates with Grignard Reagents

    PubMed Central

    2016-01-01

    α-Allenols are attractive and versatile compounds whose preparation can be a nontrivial task. In this Letter, we provide a method for the prompt synthesis of substituted α-allenols via a catalytic cross-coupling reaction which makes use of a nontoxic and cost-effective iron catalyst. The catalyst loading is typically as low as 1–5 mol %. The mild reaction conditions (−20 °C) and the short reaction time (15 min) allow for the presence of a variety of functional groups. Moreover, the reaction was shown to be scalable up to gram-scale and the propargyl substrates are readily accessible by a one-pot synthesis. PMID:27840771

  12. 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.

  13. An Iron-Catalyzed Bond-Making/Bond-Breaking Cascade Merges Cycloisomerization and Cross-Coupling Chemistry.

    PubMed

    Echeverria, Pierre-Georges; Fürstner, Alois

    2016-09-05

    Treatment of readily available enynes with alkyl-Grignard reagents in the presence of catalytic amounts of Fe(acac)3 engenders a remarkably facile and efficient reaction cascade that results in the net formation of two new C-C bonds while a C-Z bond in the substrate backbone is broken. Not only does this new manifold lend itself to the extrusion of heteroelements (Z=O, NR), but it can even be used for the cleavage of activated C-C bonds. The reaction likely proceeds via metallacyclic intermediates, the iron center of which gains ate character before reductive elimination occurs. The overall transformation represents a previously unknown merger of cycloisomerization and cross-coupling chemistry. It provides ready access to highly functionalized 1,3-dienes comprising a stereodefined tetrasubstituted alkene unit, which are difficult to make by conventional means.

  14. 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. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Uncovering the Mechanism of the Ag(I)/Persulfate-Catalyzed Cross-Coupling Reaction of Arylboronic Acids and Heteroarenes

    PubMed Central

    Patel, Niki R.; Flowers, Robert A.

    2013-01-01

    The catalytic cross-coupling of arylboronic acids with pyridines through single electron oxidation provides efficient access to substituted heterocycles. Although important, there is very little known about the mechanism of the reaction and as a consequence, it is unclear if the full scope of the transformation has been realized. In this communication we present kinetic and spectroscopic evidence showing a high degree of complexity in the reaction system. The mechanism derived from these studies shows the activation of Ag(I) for reduction of persulfate and an off-cycle protodeboronation by pyridine substrate. These results provide key mechanistic insights that enable control of the off-cycle process thus providing higher efficiency and yield. PMID:23477364

  16. Palladium-catalyzed carbonylative Sonogashira coupling of aryl bromides via tert-butyl isocyanide insertion.

    PubMed

    Tang, Ting; Fei, Xiang-Dong; Ge, Zhi-Yuan; Chen, Zhong; Zhu, Yong-Ming; Ji, Shun-Jun

    2013-04-05

    A simple and efficient palladium-catalyzed carbonylative Sonogashira coupling via tert-butyl isocyanide insertion has been developed, which demonstrates the utility of isocyanides in intermolecular C-C bond construction. This methodology provides a novel pathway for the synthesis of alkynyl imines which can undergo simple silica gel catalyzed hydrolysis to afford alkynones. The approach is tolerant of a wide range of substrates and applicable to library synthesis.

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

    PubMed

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

    2013-09-09

    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).

  18. Suzuki-Miyaura cross-coupling reactions of aryl tellurides with potassium aryltrifluoroborate salts.

    PubMed

    Cella, Rodrigo; Cunha, Rodrigo L O R; Reis, Ana E S; Pimenta, Daniel C; Klitzke, Clécio F; Stefani, Hélio A

    2006-01-06

    [reaction: see text] Palladium(0)-catalyzed cross-coupling between potassium aryltrifluoroborate salts and aryl tellurides proceeds readily to afford the desired biaryls in good to excellent yield. The reaction seems to be unaffected by the presence of electron-withdrawing or electron-donating substituents in both the potassium aryltrifluoroborate salts and aryl tellurides partners. Biaryls containing a variety of functional groups can be prepared. A chemoselectivity study was also carried out using aryl tellurides bearing halogen atoms in the same compound. In addition, this new version of the Suzuki-Miyaura cross-coupling reaction was monitored by electrospray ionization mass spectrometry where some reaction intermediates were detected and analyzed.

  19. Synthesis of a Crushed Fullerene C60H24 through Sixfold Palladium-Catalyzed Arylation.

    PubMed

    Dorel, Ruth; de Mendoza, Paula; Calleja, Pilar; Pascual, Sergio; González-Cantalapiedra, Esther; Cabello, Noemí; Echavarren, Antonio M

    2016-07-01

    The synthesis of a new C3v -symmetric crushed fullerene C60H24 (5) has been accomplished in three steps from truxene through sixfold palladium-catalyzed intramolecular arylation of a syn-trialkylated truxene precursor. Laser irradiation of 5 induces cyclodehydrogenation processes that result in the formation of C60, as detected by LDI-MS.

  20. Efficient palladium-catalyzed coupling reactions of aryl bromides and chlorides with phenols.

    PubMed

    Hu, Tongjie; Schulz, Thomas; Torborg, Christian; Chen, Xiaorong; Wang, Jun; Beller, Matthias; Huang, Jun

    2009-12-21

    A convenient and general palladium-catalyzed coupling reaction of aryl bromides and chlorides with phenols was developed. Various functional groups such as nitriles, aldehydes, ketones and esters are well tolerated and the corresponding products are obtained in good to excellent yield.

  1. Palladium-catalyzed conversion of aryl and vinyl triflates to bromides and chlorides.

    PubMed

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

    2010-10-13

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

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

    PubMed Central

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

    2010-01-01

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

  3. Palladium-catalyzed carbonylation reaction of aryl bromides with 2-hydroxyacetophenones to form flavones.

    PubMed

    Wu, Xiao-Feng; Neumann, Helfried; Beller, Matthias

    2012-10-01

    Flavone of the month: a general and efficient method for the palladium-catalyzed carbonylative synthesis of flavones has been developed. Starting from aryl bromides and 2-hydroxyacetophenones, the corresponding flavones have been isolated in good yields. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Palladium-catalyzed amination of unprotected five-membered heterocyclic bromides.

    PubMed

    Su, Mingjuan; Hoshiya, Naoyuki; Buchwald, Stephen L

    2014-02-07

    An efficient method for the palladium-catalyzed amination of unprotected bromoimidazoles and bromopyrazoles is presented. The transformation is facilitated by the use of our newly developed Pd precatalyst based on the bulky biarylphosphine ligand tBuBrettPhos (L4). The mild reaction conditions employed allow for the preparation of a broad scope of aminoimidazoles and aminopyrazoles in moderate to excellent yields.

  5. Palladium-catalyzed addition of disulfides and diselenides to alkynes under solvent free conditions.

    PubMed

    Ananikov, Valentine P; Beletskaya, Irina P

    2004-02-07

    An efficient methodology was developed for performing palladium-catalyzed E-E (E = S, Se) bond addition to alkynes under solvent free conditions. Compared to reaction in solvent significant enhancement of reaction rate, improved efficiency and remarkable catalyst stability were observed under solvent free conditions. The addition reactions were carried out with high stereoselectivity and yields in a short reaction time.

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

    PubMed

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

    2014-12-07

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

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

    PubMed Central

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

    2014-01-01

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

  8. 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. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Palladium-catalyzed decarboxylative ortho-arylation of 2-pyridyl sulfoxides with benzoyl peroxides.

    PubMed

    Sun, Meng; Wang, Zhe; Wang, Jiaxin; Guo, Peiyu; Chen, Xiangxiang; Li, Ya-Min

    2016-12-07

    A palladium catalyzed efficient strategy for regio-selective ortho-arylation of sulfoxides with benzoyl peroxides via decarboxylation has been developed. This reaction proceeds smoothly, tolerates a variety of functional groups, and provides easy access to the synthesis of different biaryl compounds.

  10. Highly efficient ligands for palladium-catalyzed asymmetric alkylation of ketone enolates.

    PubMed

    You, S L; Hou, X L; Dai, L X; Zhu, X Z

    2001-01-25

    [figure: see text] Ferrocene-modified chiral pocket ligands have been studied in the palladium-catalyzed asymmetric alkylation of simple ketone enolates, in which (R,R,Sp,Sp)-1 containing two pairs of matched chiralities, central chirality and planar chirality, behaved very efficiently in this reaction and up to 95% ee value was achieved.

  11. Palladium complexes with a tridentate PNO ligand. Synthesis of eta1-allyl complexes and cross-coupling reactions promoted by boron compounds.

    PubMed

    Crociani, Bruno; Antonaroli, Simonetta; Burattini, Marcello; Paoli, Paola; Rossi, Patrizia

    2010-04-21

    The iminophosphine 2-(2-Ph(2)P)C(6)H(4)N=CHC(6)H(4)OH (P-N-OH) reacts with [Pd(mu-Cl)(eta(3)-C(3)H(5))](2) yielding [PdCl(P-N-O)] and propene. In the presence of NEt(3), the reaction of P-N-OH with [Pd(mu-Cl)(eta(3)-1-R(1),3-R(2)C(3)H(3))](2) (R(1) = R(2) = H, Ph; R(1) = H, R(2) = Ph) affords the eta(1)-allyl derivatives [Pd(eta(1)-1-R(1),3-R(2)C(3)H(3))](P-N-O)] (R(1) = R(2) = H: 1; R(1) = H, R(2) = Ph: 2; R(1) = R(2) = Ph: 3). In solution, the complexes 1 and 3 undergo a slow dynamic process which interconverts the bonding site of the allyl ligand. The X-ray structural analysis of 1 indicates a square-planar coordination geometry around the palladium centre with a P,N,O,-tridentate ligand and a sigma bonded allyl group. The complexes [PdR(P-N-O)] (R = C(6)H(4)Me-4, C[triple bond]CPh) react slowly with p-bromoanisole in the presence of p-tolylboronic acid to give [PdBr(P-N-O)] and the coupling product RC(6)H(4)OMe-4. The latter reactions also proceed at a low rate under catalytic conditions. The coupling of allyl bromide with p-tolylboronic acid is catalyzed by [PdCl(P-N-O)]/K(2)CO(3) to give 4-allyltoluene.

  12. Exploiting the dual role of ethynylbenziodoxolones in gold-catalyzed C(sp)-C(sp) cross-coupling reactions.

    PubMed

    Banerjee, Somsuvra; Patil, Nitin T

    2017-07-11

    Reported herein is the gold-catalyzed alkynylation of terminal alkynes using ethynylbenziodoxolones (EBXs), where EBXs serve a dual role as oxidants as well as alkyne transfer agents to access unsymmetrical 1,3-diynes. Hence, the catalytic system requires no external oxidants and is compatible with a broad range of substrates, including those with polar functional groups such as NH, OH and B(OH)2.

  13. Palladium-Catalyzed Synthesis of Conjugated Allenynes via Decarboxylative Coupling.

    PubMed

    Smith, Mary K; Tunge, Jon A

    2017-09-29

    A new strategy to access conjugated allenynes via a decarboxylative coupling of propargyl esters of propiolates has been developed. In this process, allenyl-palladium intermediates are coupled with acetylides that are generated in situ to form the conjugated allenynes. Finally, the coupling is demonstrated to be highly stereospecific, providing a route to enantioenriched allenes.

  14. Palladium-Catalyzed α-Arylation of Benzylic Phosphine Oxides

    PubMed Central

    Montel, Sonia; Jia, Tiezheng

    2014-01-01

    A novel approach to prepare diarylmethyl phosphine oxides from benzyl phosphine oxides via deprotonative cross-coupling processes (DCCP) is reported. The optimization of the reaction was guided by High-Throughput Experimentation (HTE) techniques. The Pd(OAc)2/Xantphos-based catalyst enabled the reaction between benzyl diphenyl or dicyclohexyl phosphine oxide derivatives and aryl bromides in good to excellent yields (51–91%). PMID:24295336

  15. 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. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Improved synthesis of aryltriethoxysilanes via palladium(0)-catalyzed silylation of aryl iodides and bromides with triethoxysilane.

    PubMed

    Manoso, A S; DeShong, P

    2001-11-02

    The scope of the palladium-catalyzed silylation of aryl halides with triethoxysilane has been expanded to include aryl bromides. A more general Pd(0) catalyst/ligand system has been developed that activates bromides and iodides: palladium(0) dibenzylideneacetone (Pd(dba)(2)) is activated with 2-(di-tert-butylphosphino)biphenyl (Buchwald's ligand) (1:2 mol ratio of Pd/phosphine). Electron-rich para- and meta-substituted aryl halides (including unprotected aniline and phenol derivatives) undergo silylation to form the corresponding aryltriethoxysilane in fair to excellent yield; however, ortho-substituted aryl halides failed to be silylated.

  17. Synthesis of annulated 2H-indazoles and 1,2,3- and 1,2,4-triazoles via a one-pot palladium-catalyzed alkylation/direct arylation reaction.

    PubMed

    Laleu, Benoît; Lautens, Mark

    2008-11-21

    A variety of six-membered-ring annulated 2H-indazoles and 1,2,3- and 1,2,4-triazoles were synthesized in good to excellent yields from the corresponding bromoethyl azoles and aryl iodides. The annulation process involves a one-pot norbornene-mediated palladium-catalyzed sequence whereby an alkyl-aryl bond and an aryl-heteroaryl bond are successively formed through two C-H bond activations. Subsequent functionalizations of the resulting polycyclic through cross-coupling reactions are also presented.

  18. Highly selective synthesis of conjugated dienoic and trienoic esters via alkyne elementometalation–Pd-catalyzed cross-coupling

    PubMed Central

    Wang, Guangwei; Mohan, Swathi; Negishi, Ei-ichi

    2011-01-01

    All four stereoisomers (7–10) of ethyl undeca-2,4-dienoate were prepared in ≥98% isomeric purity by Pd-catalyzed alkenylation (Negishi coupling) using ethyl (E)- and (Z)-β-bromoacrylates. Although the stereoisomeric purity of the 2Z,4E-isomer (8) prepared by Suzuki coupling using conventional alkoxide and carbonate bases was ≤ 95%, as reported earlier, the use of CsF or nBu4NF as a promoter base has now been found to give all of 7–10 in ≥98% selectivity. Other widely known methods reveal considerable limitations. Heck alkenylation was satisfactory for the syntheses of the 2E,4E and 2E,4Z isomers of ≥98% purity, but the purity of the 2Z,4E isomer was ≤ 95%. Mutually complementary Horner–Wadsworth–Emmons and Still–Gennari (SG) olefinations are also of considerably limited scopes. Neither 2E,4Z nor 2Z,4Z isomer is readily prepared in ≥90% selectivity. In addition to (2Z,4E)-dienoic esters, some (2Z,4E,6E)- and (2Z,4E,6Z)-trienoic esters have been prepared in ≥98% selectivity by a newly devised Pd-catalyzed alkenylation–SG olefination tandem process. As models for conjugated higher oligoenoic esters, all eight stereoisomers for ethyl trideca-2,4,6-trienoate (23–30) have been prepared in ≥98% overall selectivity. PMID:21709262

  19. Highly selective synthesis of conjugated dienoic and trienoic esters via alkyne elementometalation-Pd-catalyzed cross-coupling.

    PubMed

    Wang, Guangwei; Mohan, Swathi; Negishi, Ei-ichi

    2011-07-12

    All four stereoisomers (7-10) of ethyl undeca-2,4-dienoate were prepared in ≥ 98% isomeric purity by Pd-catalyzed alkenylation (Negishi coupling) using ethyl (E)- and (Z)-β-bromoacrylates. Although the stereoisomeric purity of the 2Z,4E-isomer (8) prepared by Suzuki coupling using conventional alkoxide and carbonate bases was ≤ 95%, as reported earlier, the use of CsF or (n)Bu(4)NF as a promoter base has now been found to give all of 7-10 in ≥ 98% selectivity. Other widely known methods reveal considerable limitations. Heck alkenylation was satisfactory for the syntheses of the 2E,4E and 2E,4Z isomers of ≥ 98% purity, but the purity of the 2Z,4E isomer was ≤ 95%. Mutually complementary Horner-Wadsworth-Emmons and Still-Gennari (SG) olefinations are also of considerably limited scopes. Neither 2E,4Z nor 2Z,4Z isomer is readily prepared in ≥ 90% selectivity. In addition to (2Z,4E)-dienoic esters, some (2Z,4E,6E)- and (2Z,4E,6Z)-trienoic esters have been prepared in ≥ 98% selectivity by a newly devised Pd-catalyzed alkenylation-SG olefination tandem process. As models for conjugated higher oligoenoic esters, all eight stereoisomers for ethyl trideca-2,4,6-trienoate (23-30) have been prepared in ≥ 98% overall selectivity.

  20. Palladium- (and nickel-) catalyzed vinylation of aryl halides†

    PubMed Central

    Denmark, Scott E.; Butler, Christopher R.

    2009-01-01

    Functionalized styrenes are extremely useful building blocks for organic synthesis and for functional polymers. One of the most general syntheses of styrenes involves the combination of an aryl halide with a vinyl organometallic reagent under catalysis by palladium or nickel complexes. This Feature Article provides the first comprehensive summary of the vinylation methods currently available along with a critical comparison of the efficiency, cost and scope of the methods. PMID:19081992

  1. 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)

  2. 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

    2015-10-05

    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.

  3. Palladium-catalyzed C-F activation of polyfluoronitrobenzene derivatives in Suzuki-Miyaura coupling reactions.

    PubMed

    Cargill, Matthew R; Sandford, Graham; Tadeusiak, Andrezj J; Yufit, Dmitrii S; Howard, Judith A K; Kilickiran, Pinar; Nelles, Gabrielle

    2010-09-03

    Highly fluorinated nitrobenzene derivatives are suitable substrates for palladium-catalyzed C-F bond arylation using readily available palladium catalysts under both conventional heating and microwave conditions. Arylation occurs ortho to the nitro group offering a synthetic route to polyfluorinated 2-arylnitrobenzene systems. The regiochemistry of the arylation reactions suggests that there is a significant directing interaction between the nitro group and the incoming nucleophilic palladium catalyst which is facilitated by the presence of several fluorine atoms attached the ring. Investigations into the regioselectivity and reactivity of several tetrafluoro- and trifluoronitrobenzene derivatives provides further evidence for the highly nucleophilic character of the oxidative addition step in contrast to the concerted mechanism of more conventional Suzuki-Miyaura coupling reactions involving aryl iodides and bromides.

  4. 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.

  5. 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.

  6. Palladium-Catalyzed Amination of Unprotected Five-Membered Heterocyclic Bromides

    PubMed Central

    2015-01-01

    An efficient method for the palladium-catalyzed amination of unprotected bromoimidazoles and bromopyrazoles is presented. The transformation is facilitated by the use of our newly developed Pd precatalyst based on the bulky biarylphosphine ligand tBuBrettPhos (L4). The mild reaction conditions employed allow for the preparation of a broad scope of aminoimidazoles and aminopyrazoles in moderate to excellent yields. PMID:24417224

  7. Direct Palladium-Catalyzed Carbonylative Transformation of Allylic Alcohols and Related Derivatives.

    PubMed

    Wu, Fu-Peng; Peng, Jin-Bao; Fu, Lu-Yang; Qi, Xinxin; Wu, Xiao-Feng

    2017-09-18

    A direct, palladium-catalyzed, carbonylative transformation of allylic alcohols for the synthesis of β,γ-unsaturated carboxylic acids has been developed. With formic acid as the CO source, various allylic alcohols were conveniently transformed into the corresponding β,γ-unsaturated carboxylic acids with excellent linear and (E)-selectivity. The reaction was performed under mild conditions; toxic CO gas manipulation and high-pressure equipment were avoided in this procedure.

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

    PubMed Central

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

    2012-01-01

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

  9. Enantioselective palladium-catalyzed dearomative cyclization for the efficient synthesis of terpenes and steroids.

    PubMed

    Du, Kang; Guo, Pan; Chen, Yuan; Cao, Zhen; Wang, Zheng; Tang, Wenjun

    2015-03-02

    A novel enantioselective palladium-catalyzed dearomative cyclization has been developed for the efficient construction of a series of chiral phenanthrenone derivatives bearing an all-carbon quaternary center. The effectiveness of this method in the synthesis of terpenes and steroids was demonstrated by a highly efficient synthesis of a kaurene intermediate, the facile construction of the skeleton of the anabolic steroid boldenone, and the enantioselective total synthesis of the antimicrobial diterpene natural product (-)-totaradiol.

  10. Palladium-catalyzed vinylation of aminals with simple alkenes: a new strategy to construct allylamines.

    PubMed

    Xie, Yinjun; Hu, Jianhua; Wang, Yanyu; Xia, Chungu; Huang, Hanmin

    2012-12-26

    A novel, highly selective palladium-catalyzed vinylation reaction for the direct synthesis of allylic amines from styrenes and aminals has been established. The utility of this method was also demonstrated by the rapid synthesis of cinnarizine from aldehydes, amines, and simple alkenes in one-pot manner. Mechanistic studies suggested that the reaction proceeds through a valuable cyclometalated Pd(II) complex generated by the oxidative addition of aminal to a Pd(0) species.

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

    PubMed

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

    2017-02-01

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

  12. Development of a palladium-catalyzed α-arylation of cyclopropyl nitriles.

    PubMed

    McCabe Dunn, Jamie M; Kuethe, Jeffrey T; Orr, Robert K; Tudge, Matthew; Campeau, Louis-Charles

    2014-12-19

    1,1-Disubstituted aryl cyclopropyl nitriles are useful moieties in biologically active compounds and provide access to a range of cyclopropyl derivatives. Herein, we describe the development of a palladium-catalyzed α-arylation of cyclopropyl, cyclobutyl, and cyclopentyl nitriles that affords these functional groups in one step from a variety of aryl bromides in good to excellent yields. Furthermore, we demonstrate the transformation of aryl cyclopropyl nitriles into aryl trifluoromethyl cyclopropanes.

  13. Palladium-catalyzed oxidative carbonylation of N-allylamines for the synthesis of β-lactams.

    PubMed

    Li, Wu; Liu, Chao; Zhang, Heng; Ye, Keyin; Zhang, Guanghui; Zhang, Wangzheng; Duan, Zhengli; You, Shuli; Lei, Aiwen

    2014-02-24

    β-Lactam scaffolds are considered to be ideal building blocks for the synthesis of nitrogen-containing compounds. A new palladium-catalyzed oxidative carbonylation of N-allylamines for the synthesis of α-methylene-β-lactams is reported. DFT calculations suggest that the formation of β-lactams via a four-membered-ring transition state is favorable. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Chelation-assisted palladium-catalyzed direct cyanation of 2-arylpyridine C-H bonds.

    PubMed

    Jia, Xiaofei; Yang, Dongpeng; Zhang, Shouhui; Cheng, Jiang

    2009-10-15

    A chelation-assisted palladium-catalyzed ortho-cyanation of the sp2 C-H bond by CuCN provided aromatic nitriles in moderate to good yields. Notably, the reaction could be conducted on a 10 mmol scale. The key intermediate of the natural product of Menispermum dauricum DC was concisely synthesized by the procedure. This new approach represents an exceedingly practical method for the synthesis of aromatic nitriles and offers an attractive alternative to the traditional Sandmeyer reaction.

  15. Palladium-catalyzed regio- and enantioselective fluorination of acyclic allylic halides.

    PubMed

    Katcher, Matthew H; Sha, Allen; Doyle, Abigail G

    2011-10-12

    This report describes the Pd(0)-catalyzed fluorination of linear allylic chlorides and bromides, yielding branched allylic fluorides in high selectivity. Many of the significant synthetic limitations previously associated with the preparation of these products are overcome by this catalytic method. We also demonstrate that a chiral bisphosphine-ligated palladium catalyst enables highly enantioselective access to a class of branched allylic fluorides that can be readily diversified to valuable fluorinated products.

  16. trans-Chloro(1-naphthyl)bis(triphenylphosphine)nickel(II)/PCy3 catalyzed cross-coupling of aryl and heteroaryl neopentylglycolboronates with aryl and heteroaryl mesylates and sulfamates at room temperature.

    PubMed

    Leowanawat, Pawaret; Zhang, Na; Safi, Mehtap; Hoffman, David J; Fryberger, Miriam C; George, Aiswaria; Percec, Virgil

    2012-03-16

    trans-Chloro(1-naphthyl)bis(triphenylphosphine)nickel(II) complex/PCy(3) system has been successfully applied as catalyst for the Suzuki-Miyaura cross-coupling of aryl and heteroaryl neopentylglycolboronates with aryl and heteroaryl mesylates and sulfamates in THF at room temperature. This cross-coupling reaction tolerates various functional groups, including keto, imino, ester, ether, and cyano. Together with the nickel-catalyzed, one-pot, two-step neopentylglycolborylation, this bench stable and inexpensive Ni(II)-based catalyst can be utilized as an alternative to Ni(COD)(2)/PCy(3) to provide an inexpensive, robust, and convenient synthesis of biaryl and heterobiaryl compounds.

  17. Mechanistic Insight into the Cu-Catalyzed C-S Cross-Coupling of Thioacetate with Aryl Halides. A Joint Experimental-Computational Study.

    PubMed

    Soria-Castro, Silvia M; Andrada, Diego M; Caminos, Daniel A; Argúello, Juan E; Robert, Marc; Peñeñory, Alicia B

    2017-09-29

    The mechanism of the Ullmann-type reaction between potassium thioacetate (KSAc) and iodobenzene (PhI) catalyzed by CuI associated with 1,10-phenanthroline (phen) as a ligand has been explored experimentally and computationally. The study on C-S bond formation has been investigated by UV-visible spectrophotometry, cyclic voltammetry, mass espectrometry and products assessment from radical probes. The results indicate that under experimental conditions the catalytically active species is [Cu(phen)(SAc)] regardless of the copper source. An examination of the aryl halide activation mechanism using radical probes was undertaken. No evidences of the presence of radical species have been found during the reaction process, which is consistent with an oxidative addition cross coupling pathway. The different reaction pathways leading to the experimentally observed reaction products have been studied by DFT calculation. The oxidative addition - reductive elimination mechanism via an unstable CuIII intermediate is energetically more feasible than other possible mechanisms such as Single Electron Transfer, Halogen Atom Transfer and σ-Bond Methatesis.

  18. Density functional theory studies of negishi alkyl-alkyl cross-coupling reactions catalyzed by a methylterpyridyl-Ni(I) complex.

    PubMed

    Lin, Xufeng; Phillips, David Lee

    2008-05-16

    Density functional theory calculations were done to examine the potential energy surfaces of Ni(I)-catalyzed Negishi alkyl-alkyl cross-coupling reactions by using propyl iodide and isopropyl iodide as model alkyl electrophiles and CH 3ZnI as a model alkyl nucleophile. A four-step catalytic cycle involving iodine transfer, radical addition, reductive elimination, and transmetalation steps were characterized structurally and energetically. The reaction mechanism for this catalytic cycle appears feasible based on the calculated free energy profiles for the reactions. The iodine transfer step is the rate-determining step for the Ni(tpy)-CH 3 (tpy = 2,2'6',2''-terpyridine) reactions with alkyl iodides. For secondary alkyl electrophiles, the oxidative addition intermediate, Ni(III), prefers to undergo decomposition over reductive elimination, whereas for the primary alkyl electrophiles, Ni(III) prefers to undergo reductive elimination over decomposition based on comparison of the relative reaction rates for these two types of steps. In addition, thermodynamic data were employed to help explain why the yield of the coupled product is very low from the Ni(II)-alkyl halide reactions with organozinc reagents.

  19. Palladium-Catalyzed Aerobic Dehydrogenation of Substituted Cyclohexanones to Phenols

    PubMed Central

    Izawa, Yusuke; Pun, Doris; Stahl, Shannon S.

    2011-01-01

    Aromatic molecules are key constituents of many pharmaceuticals, electronic materials and commodity plastics. The utility of these molecules directly reflects the identity and pattern of substituents on the aromatic ring. Here, we report the discovery of a palladium(II) catalyst system, incorporating an unconventional ortho-dimethylaminopyridine ligand, for the conversion of substituted cyclohexanones to the corresponding phenols. The reaction proceeds via successive dehydrogenation of two saturated carbon-carbon bonds of the six-membered ring and uses molecular oxygen as the hydrogen acceptor. This reactivity demonstrates a versatile and efficient strategy for the synthesis of substituted aromatic molecules with fundamentally different selectivity constraints from the numerous existing synthetic methods that rely on substitution of a pre-existing aromatic ring. PMID:21659567

  20. Palladium-catalyzed heck coupling reaction of aryl bromides in aqueous media using tetrahydropyrimidinium salts as carbene ligands.

    PubMed

    Yaşar, Sedat; Ozcan, Emine Ozge; Gürbüz, Nevin; Cetinkaya, Bekir; Ozdemir, Ismail

    2010-01-28

    An efficient and stereoselective catalytic system for the Heck cross coupling reaction using novel 1,3-dialkyl-3,4,5,6-tetrahydropyrimidinium salts (1, LHX) and Pd(OAc)2 loading has been reported. The palladium complexes derived from the salts 1a-f prepared in situ exhibit good catalytic activity in the Heck coupling reaction of aryl bromides under mild conditions.

  1. Mechanistic Insights into the Aerobic Cu(I)-Catalyzed Cross-Coupling of S-Acyl Thiosalicylamide Thiol Esters and Boronic Acids

    PubMed Central

    Varela-Álvarez, Adrián; Liebeskind, Lanny S.; Musaev, Djamaladdin G.

    2012-01-01

    The Density Functional Theory (DFT) method is used to elucidate the nature of the active species and the mechanism of the aerobic CuI-catalyzed cross-coupling of S-acyl thiosalicylamide thiol esters and boronic acids reported previously (J. Am. Chem. Soc. 2007, 129, 15734–15735; Angew. Chem., Int. Ed. 2009, 48, 1417-1421). The energetically lowest isomer of the proposed active species [LC(O)R1]Cu-(O2)-Cu[LC(O)R1]2+, 2a, (where L = thiolatosalicylamide) is found to be I1(OO,OO) with a μ-η2:η2-peroxo Cu2O2-core, while its isomers I2(OO,OO) with a bis-(μ-O) Cu2O2-core and I3(OO,OO) with a (μ-η1:η1) Cu2O2-core lie only a few kcal/mol higher and separated by 4–7kcal/mol energy barriers. In all these isomers, the thiol ester is coordinated to the Cu-centers via its two O-ends. Isomers with (SO,OO) and (SO,SO) coordination modes of the thiol esters lie slightly higher and are separated with moderate energy barriers. We found the latter isomers to be vital for the reported CuI-templated cross-coupling of S-acyl thiosalicylamide thiol esters and boronic acids under aerobic conditions. The presence of an anion (halide, carboxylate modeled as formate) in the reaction medium is found to be necessary. Its coordination to the active catalyst I1(SO,SO) is the first step of the proposed anion-assisted transmetalation by boronic acid. Overall the transmetalation reaction requires 34.0 kcal/mol and is 24.0 kcal/mol exergonic. This conclusion is in reasonable agreement with available experiments. The C-C bond formation in the transmetalation product requires a 6.3 kcal/mol lower energy barrier and is highly exergonic. PMID:23565023

  2. 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

  3. Palladium-Catalyzed Reactions of Arylindium Reagents Prepared Directly from Aryl Iodides and Indium Metal

    PubMed Central

    Papoian, Vardan

    2008-01-01

    Treatment of aryl iodides with indium metal in the presence of lithium chloride leads to the formation of an organoindium reagent capable of participating in cross-coupling reactions under transition-metal catalysis. Combination with aryl halides in the presence of 5 mol% Cl2Pd(dppf) furnishes biaryl compounds in good yields; similarly, reaction with acyl halides or allylic acetates/carbonates in the presence of 5–10 mol % palladium catalyst leads to arylketones and allylic substitution products, respectively, in moderate yields. The reactions are tolerant of the presence of protic solvents, and ~85% of the indium metal employed can be recovered by reduction of the residual indium salts with zinc(0). PMID:18722408

  4. Palladium-catalyzed direct ortho C-H arylation of 2-arylpyridine derivatives with aryltrimethoxysilane.

    PubMed

    Li, Wu; Yin, Zhangwei; Jiang, Xiaoqing; Sun, Peipei

    2011-10-21

    A Pd(OAc)(2)-catalyzed cross-coupling reaction between 2-arylpyridine and aryltrimethoxysilane in the presence of AgF and BQ in 1,4-dioxane was studied. After various reaction parameters (catalyst, oxidant, additive, solvent and reaction temperature) were examined, the optimal conditions for the reaction were identified. The synthesis is compatible to aryltrimethoxysilane with both electron-withdrawing and electron-donating groups on the aryl moiety with moderate yields. The kinetic isotope effect (k(H)/k(D)) for the C-H bond activation was provided.

  5. An electrochemical nickel-catalyzed arylation of 3-amino-6-chloropyridazines.

    PubMed

    Sengmany, Stéphane; Vitu-Thiebaud, Arnaud; Le Gall, Erwan; Condon, Sylvie; Léonel, Eric; Thobie-Gautier, Christine; Pipelier, Muriel; Lebreton, Jacques; Dubreuil, Didier

    2013-01-18

    3-Amino-6-aryl- and 3-amino-6-heteroarylpyridazines have been obtained in generally good yield using a nickel-catalyzed electrochemical cross-coupling between 3-amino-6-chloropyridazines and aryl or heteroaryl halides at room temperature. Comparative experiments involving classical palladium-catalyzed reactions, such as Suzuki, Stille, or Negishi cross-couplings, reveal that the electrochemical method can constitute a reliable alternative tool for biaryl formation. A possible reaction mechanism is proposed on the basis of electrochemical analyses.

  6. 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

  7. Role of planar chirality of S,N- and P,N-ferrocene ligands in palladium-catalyzed allylic substitutions.

    PubMed

    You, Shu-Li; Hou, Xue-Long; Dai, Li-Xin; Yu, Yi-Hua; Xia, Wei

    2002-07-12

    Palladium-catalyzed asymmetric allylic substitutions using thioether and phosphino derivatives of ferrocenyloxazoline as ligands have been investigated with a focus on studying the role of planar chirality. In allylic alkylation, up to 98% ee and 95% ee were achieved with S,N- and P,N-ligands, respectively. In allylic amination, 97% ee was realized with P,N-ligands in the presence of TBAF. Several palladium allylic complexes were characterized by X-ray diffraction and/or solution NMR. Thioether derivatives of ferrocenyloxazolines with only planar chirality showed lower enantioselectivity in the allylic alkylation except 5c because of the formation of a new chirality on sulfur atom during the coordination of sulfur with palladium. On the other hand, in the planar chiral P,N-ligands without central chirality, (Sp)-11a-c there was no such disturbance and comparatively higher enantioselectivity in both palladium-catalyzed allylic alkylation and amination was provided.

  8. Palladium-Catalyzed Allylic C-H Bond Functionalization of Olefins

    NASA Astrophysics Data System (ADS)

    Liu, Guosheng; Wu, Yichen

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

  9. 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

  10. Efficient Palladium-Catalyzed Alkoxycarbonylation of Bulk Industrial Olefins Using Ferrocenyl Phosphine Ligands.

    PubMed

    Dong, Kaiwu; Sang, Rui; Fang, Xianjie; Franke, Robert; Spannenberg, Anke; Neumann, Helfried; Jackstell, Ralf; Beller, Matthias

    2017-05-02

    The development of ligands plays a key role and provides important innovations in homogeneous catalysis. In this context, we report a novel class of ferrocenyl phosphines for the alkoxycarbonylation of industrially important alkenes. A basic feature of our ligands is the combination of sterically hindered and amphoteric moieties on the P atoms, which leads to improved activity and productivity for alkoxycarbonylation reactions compared to the current industrial state-of-the-art ligand 1,2-bis((di-tert-butylphosphino)methyl)benzene). Advantageously, palladium catalysts with these novel ligands also enable such transformations without additional acid under milder reaction conditions. The practicability of the optimized ligand was demonstrated by preparation on >10 g scale and its use in palladium-catalyzed carbonylations on kilogram scale. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. 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.

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

    PubMed Central

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

    2013-01-01

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

  13. Palladium-Catalyzed Hydrolytic Cleavage of Aromatic C-O Bonds.

    PubMed

    Wang, Meng; Shi, Hui; Camaioni, Donald M; Lercher, Johannes A

    2017-02-13

    Metallic palladium surfaces are highly selective in promoting the reductive hydrolysis of aromatic ethers in aqueous phase at relatively mild temperatures and pressures of H2 . At quantitative conversions, the selectivity to hydrolysis products of PhOR ethers was observed to range from 50 % (R=Ph) to greater than 90 % (R=n-C4 H9 , cyclohexyl, and PhCH2 CH2 ). By analysis of the evolution of products with and without incorporation of H2(18) O, the pathway was concluded to be initiated by palladium metal catalyzed partial hydrogenation of the phenyl group to an enol ether. Water then rapidly adds to the enol ether to form a hemiacetal, which then undergoes elimination to cyclohexanone and phenol/alkanol products. A remarkable feature of the reaction is that the stronger Ph-O bond is cleaved rather than the weaker aliphatic O-R bond.

  14. Palladium-Catalyzed Fluoroarylation of gem-Difluoroalkenes.

    PubMed

    Tang, Hai-Jun; Lin, Ling-Zhi; Feng, Chao; Loh, Teck-Peng

    2017-08-07

    A Pd-catalyzed fluoroarylation of gem-difluoroalkenes with aryl halides is reported. By taking advantage of the in situ generated α-CF3 -benzylsilver intermediates derived from the nucleophilic addition of silver fluoride to gem-difluoroalkenes, this strategy bypasses the use of a strong base, thus enabling a mild and general synthetic method for ready access to non-symmetric α,α-disubstituted trifluoroethane derivatives. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Enantioselective palladium(0)-catalyzed Nazarov-type cyclization.

    PubMed

    Kitamura, Kei; Shimada, Naoyuki; Stewart, Craig; Atesin, Abdurrahman C; Ateşin, Tülay A; Tius, Marcus A

    2015-05-18

    A Pd(0)-catalyzed asymmetric Nazarov-type cyclization is described. The optimized ligand for the reaction incorporates a weakly coordinating pyridine ring into a TADDOL-derived phosphoramidite (TADDOL=α,α,α,α-tetraaryl-1,3-dioxolane-4,5-dimethanol). The reaction leads to the formation of cyclopentenones as single diastereoisomers that incorporate two contiguous asymmetric centers, one tertiary and one an all-carbon-atom quaternary stereocenter, in high yield and optical purity. It is noteworthy that the reaction does not require that substrates should be activated by aryl substituents. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Palladium-Catalyzed Tandem Carbene Migratory Insertion and Intramolecular Cyclization: Synthesis of Chromeno[4,3-b]chromene Compounds.

    PubMed

    Shang, Xue Song; Li, Nian Tai; Siyang, Hai Xiao; Liu, Pei Nian

    2015-05-01

    Chromeno[4,3-b]chromene is a ubiquitous structural motif found in various pharmaceuticals and biologically active compounds. A concise palladium-catalyzed reaction of vinyl iodides and salicyl N-tosylhydrazones has been achieved to afford a series of compounds containing the chromeno[4,3-b]chromene scaffold in moderate to high yield. This tandem reaction involves palladium(II) carbene migratory insertion and intramolecular cyclization assisted by an O nucleophile and tolerates various functional groups.

  17. An active, general, and long-lived palladium catalyst for cross-couplings of deactivated (hetero)aryl chlorides and bromides with arylboronic acids.

    PubMed

    Hoshi, Takashi; Honma, Tomonobu; Mori, Ayako; Konishi, Maki; Sato, Tsutomu; Hagiwara, Hisahiro; Suzuki, Toshio

    2013-11-15

    An active, general, and long-lived palladium catalyst for Suzuki-Miyaura reactions of aryl and heteroaryl chlorides deactivated by steric hindrance, electron richness, and coordinating functional groups is reported. In reactions of arylbromide bearing two o-tert-butyl substituents, C(sp(3))-H arylation of the tert-butyl group, rather than the Suzuki-Miyaura reaction, proceeded in excellent yield. The key to the success of the reactions was the development of biphenylene-substituted dicyclohexylruthenocenylphosphine (CyR-Phos) as a supporting ligand.

  18. 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

    2015-02-06

    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.

  19. An advantageous route to oxcarbazepine (trileptal) based on palladium-catalyzed arylations free of transmetallating agents.

    PubMed

    Carril, Mónica; SanMartin, Raul; Churruca, Fátima; Tellitu, Imanol; Domínguez, Esther

    2005-10-27

    [reaction: see text] A new route to oxcarbazepine (Trileptal), the most widely prescribed antiepileptic drug, starting from commercially available 2'-aminoacetophenone and 1,2-dibromobenzene, is reported. The sequentially accomplished key steps are palladium-catalyzed intermolecular alpha-arylation of ketone enolates and intramolecular N-arylation reactions. After several experiments to establish the best conditions for both arylation processes, the target oxcarbazepine is obtained in a satisfactory overall yield, minimizing the number of steps and employing scalable catalytic procedures developed in partially aqueous media.

  20. Palladium-catalyzed N-acylation of monosubstituted ureas using near-stoichiometric carbon monoxide.

    PubMed

    Bjerglund, Klaus; Lindhardt, Anders T; Skrydstrup, Troels

    2012-04-20

    The palladium-catalyzed carbonylation of urea derivatives with aryl iodides and bromides afforded N-benzoyl ureas (20 examples) in yields attaining quantitative via the application of near-stoichiometric amounts of carbon monoxide generated from the decarbonylation of the CO precursor, 9-methylfluorene-9-carbonyl chloride. The synthetic protocol displayed good functional group tolerance. The methodology is also highly suitable for (13)C isotope labeling, which was demonstrated through the synthesis of three benzoyl ureas, including the insecticide triflumuron, whereby (13)CO was incorporated into the core structure. © 2012 American Chemical Society

  1. Palladium-Catalyzed Aerobic Acetoxylation of Benzene using NOx-Based Redox Mediators‡

    PubMed Central

    Zultanski, Susan L.; Stahl, Shannon S.

    2015-01-01

    Palladium-catalyzed methods for C–H oxygenation with O2 as the stoichiometric oxidant are limited. Here, we describe the use of nitrite and nitrate sources as NOx-based redox mediators in the acetoxylation of benzene. The conditions completely avoid formation of biphenyl as a side product, and strongly favor formation of phenyl acetate over nitrobenzene (PhOAc:PhNO2 ratios up to 40:1). Under the optimized reaction conditions, with 0.1 mol% Pd(OAc)2, 136 turnovers of Pd are achieved with only 1 atm of O2 pressure. PMID:25843978

  2. Palladium-catalyzed tandem addition/cyclization in aqueous medium: synthesis of 2-arylindoles.

    PubMed

    Yu, Shuling; Hu, Kun; Gong, Julin; Qi, Linjun; Zhu, Jianghe; Zhang, Yetong; Cheng, Tianxing; Chen, Jiuxi

    2017-05-23

    An efficient protocol to construct 2-arylindoles was developed through palladium-catalyzed tandem addition/cyclization of potassium aryltrifluoroborates with aliphatic nitriles in aqueous medium. The use of water as the reaction medium makes the synthesis process environmentally benign. A plausible mechanism for the formation of 2-arylindoles involving sequential nucleophilic addition followed by an intramolecular cyclization is proposed. Moreover, the utility of this catalytic tandem transformation was also demonstrated in an efficient gram-scale synthesis. This method provides an alternative synthetic tool for accessing a more diverse array of 2-arylindoles.

  3. Palladium-catalyzed amination of meso-(bromophenyl)porphyrins with diamines and azamacrocycles.

    PubMed

    Mikhalitsyna, E A; Tyurin, V S; Khrustalev, V N; Lonin, I S; Beletskaya, I P

    2014-03-07

    Novel diamino and azamacrocycle functionalized porphyrins were efficiently synthesized by palladium-catalyzed amination of mono- and bis(meso-(bromophenyl))porphyrins. The optimization of reaction conditions allowed us to achieve high yields of products with substrates of different types. Supramolecular utility of the thus obtained aminoporphyrins was shown by investigations of processes of coordination self-assembly in solution by NMR and UV-Vis spectroscopy. The crystalline 1D-coordination polymer formed via self-assembly of N,N-dimethylethylenediamine substituted zinc porphyrin was characterized by X-ray diffraction.

  4. Palladium-Catalyzed Arylation of Carbasugars Enables the Discovery of Potent and Selective SGLT2 Inhibitors.

    PubMed

    Ng, Wai-Lung; Lau, Kit-Man; Lau, Clara B-S; Shing, Tony K M

    2016-10-24

    Selective inhibition of the transporter protein sodium-glucose cotransporter 2 (SGLT2) has emerged as a promising way to control blood glucose level in diabetes patients. Reported herein is a short and convergent synthetic route towards some small-molecule SGLT2 inhibitors by a chemo- and diastereospecific palladium-catalyzed arylation reaction. This synthetic strategy enabled the discovery of two highly selective and potent SGLT2 inhibitors, thereby paving the way towards the development of carbasugar SGLT2 inhibitors as potential antidiabetic/antitumor agents.

  5. Asymmetric Synthesis of Fluorinated Isoindolinones through Palladium-Catalyzed Carbonylative Amination of Enantioenriched Benzylic Carbamates.

    PubMed

    Barrio, Pablo; Ibáñez, Ignacio; Herrera, Lidia; Román, Raquel; Catalán, Silvia; Fustero, Santos

    2015-08-03

    The asymmetric synthesis of fluorinated isoindolinones has been achieved by a palladium-catalyzed aminocarbonylation reaction of the corresponding α-fluoroalkyl o-iodobenzylamines. A base-mediated anti β-hydride elimination process was suggested to explain the partial erosion of the optical purity observed in some cases. This mechanistic rationale enabled the minimization of this partial racemization by fine-tuning the pKa of the base. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Palladium-catalyzed ring-opening reactions of cyclopropanated 7-oxabenzonorbornadiene with alcohols

    PubMed Central

    Tait, Katrina; Alrifai, Oday; Boutin, Rebecca; Haner, Jamie

    2016-01-01

    Summary Palladium-catalyzed ring-opening reactions of cyclopropanated 7-oxabenzonorbornadiene derivatives using alcohol nucleophiles were investigated. The optimal conditions were found to be 10 mol % PdCl2(CH3CN)2 in methanol, offering yields up to 92%. The reaction was successful using primary, secondary and tertiary alcohol nucleophiles and was compatible with a variety of substituents on cyclopropanated oxabenzonorbornadiene. With unsymmetrical C1-substituted cyclopropanated 7-oxabenzonorbornadienes, the regioselectivity of the reaction was excellent, forming only one regioisomer in all cases. PMID:27829926

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

    PubMed Central

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

    2017-01-01

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

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

    PubMed

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

    2017-08-30

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

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

    PubMed Central

    Alvaro, Elsa

    2010-01-01

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

  10. Palladium-catalyzed asymmetric cycloadditions of vinylcyclopropanes and in situ formed unsaturated imines: construction of structurally and optically enriched spiroindolenines.

    PubMed

    Liu, Ze-Shui; Li, Wen-Ke; Kang, Tai-Ran; He, Long; Liu, Quan-Zhong

    2015-01-02

    A palladium-catalyzed (3 + 2) cycloaddition of vinyl cyclopropane and α,β-unsaturated imines generated in situ from aryl sulfonyl indoles is reported. The reaction proceeds with high diastereoselectivity to provide the optically enriched spirocyclopentane-1,3'-indolenines in up to 74% yield and with up to 97% ee, which contains an all-carbon quaternary center and two tertiary stereocenters. The reaction involves a first conjugate addition of the carbon anion of zwitterionic π-allylpalladium complex from vinyl cyclopropane to the in situ formed unsaturated imine followed by a palladium-catalyzed intramolecular C3-allylation of indole.

  11. Differential Reactivities of Enyne Substrates in Ruthenium- and Palladium-Catalyzed Cycloisomerizations

    PubMed Central

    Trost, Barry M.; Gutierrez, Alicia C.; Ferreira, Eric M.

    2010-01-01

    Complementary methods for the transition metal-catalyzed enyne cycloisomerizations of cyclic olefins have been developed. By using distinct ruthenium and palladium catalysts, decalins and 7,6-bicycles can be obtained with dichotomous stereochemical outcomes. The change in mechanism that accompanies the change in metal affords trans-fused 1,4-dienes with ruthenium and their cis-fused diastereomers under palladium catalysis. In the reactions under ruthenium catalysis, a coordinating group is required, and acts to direct the metal to the same side of the carbocycle, resulting in the observed trans diastereoselectivity. Subtle changes in the carbocyclic substrate led to the discovery of a heretofore-unobserved mechanistic pathway, providing bicyclic cycloisomerization products under palladium catalysis and tricyclic products under ruthenium catalysis in DMA. The differential effect of DMA supports a mechanism in which the coordination requirements of the two paths differ, allowing for the reaction to be shuttled through the metallacycle pathway (generating tricyclic products) when DMA is used as a solvent. PMID:20545356

  12. Nucleophilic substitutions of 1-alkenylcyclopropyl esters and 1-alkynylcyclopropyl chlorides catalyzed by palladium (0)

    SciTech Connect

    Stolle, A. |; Ollivier, J.; Salauen, J.

    1992-05-20

    The 1-ethenylcyclopropylsulfonates 2e,f and 2-cyclopropylideneethyl esters 10b,c, readily available from cyclopropanone hemiacetal 1, undergo regioselective Pd(0) catalyzed nucleophilic substitution via the unsymmetric 1,1-dimethylene-{pi}-allyl complex 23. With stabilized anions (enolates of malonic ester, {beta}-dicarbonyl compounds, {beta}-sulfonyl ester, and Schiff bases as well as acetate anion, sulfonamide anion, etc.) the nucleophilic substitution occurs at the terminal vinylic position exclusively, providing cyclopropylideneethyl derivatives as building blocks of high synthetic potential. Competition experiments have disclosed that 1-ethenylcyclopropyl tosylate (2e) and cyclopropylideneethyl acetate (10b) are more reactive than dimethylallyl acetates 19 and 22, respectively. Use of chiral phosphines as ligands in the palladium catalyst can provide optically active methylenecyclopropane derivatives. With phenyl-, methyl-, and even n-butylzinc chloride as nucleophiles, the reaction apparently proceeds with initial transfer of the organic residue to palladium, followed by reductive elimination entailing tertiary substitution on the cyclopropane ring exclusively; the same type of product is obtained with azide and bis(trimethylsilyl)amide. But the site of hydride attack to yield reduction products depends on the hydride source. 1-Alkynylcyclopropyl chlorides 12, 13, and 14 react only with organozinc chlorides (nonstabilized nucleophiles) to provide mixtures of ethenylidenecyclopropanes 65 and alkynylcyclopropanes 66, via the {sigma}-palladium complexes 69 and 70, while chloride 15 undergoes mainly reduction. Other transition metal catalysts (Ni, Mo) also induce substitutions, but with poorer regioselectivity. 81 refs., 9 figs., 3 tabs.

  13. One-pot hydrothermal synthesis of magnetically recoverable palladium/reduced graphene oxide nanocomposites and its catalytic applications in cross-coupling reactions.

    PubMed

    Fu, Wenzhi; Zhang, Zhuqing; Zhuang, Peiyuan; Shen, Jianfeng; Ye, Mingxin

    2017-07-01

    A facile, green, economical approach was designed to deposit palladium nanoparticles on magnetic reduced graphene oxide nanosheets (Pd-Fe3O4/rGO) via a one-pot hydrothermal synthesis method. The prepared Pd-Fe3O4/rGO nanocomposites were thoroughly characterized by Transmission electron microscopy, Scanning electron microscopy, Fourier-transform infrared spectroscopy, X-ray diffraction, and Raman spectroscopy. Importantly, the highly efficient catalytic property of the as-obtained Pd-Fe3O4/rGO catalyst was demonstrated for the Suzuki-Miyaura coupling reaction and Mizoroki-Heck coupling reaction. Significantly, the Suzuki-Miyaura coupling reactions could be efficiently performed in an environmentally friendly aqueous solution with no need for further additives. Besides, the nanocomposites could be conveniently separated from reaction system with an external permanent magnet for recycling and the inherent catalytic activity of the nanocomposites did not exacerbate after six repeated applications.

  14. Mild and Efficient Palladium-Catalyzed Direct Trifluoroethylation of Aromatic Systems by C-H Activation.

    PubMed

    Tóth, Balázs L; Kovács, Szabolcs; Sályi, Gergő; Novák, Zoltán

    2016-02-05

    The introduction of trifluoroalkyl groups into aromatic molecules is an important transformation in the field of organic and medicinal chemistry. However, the direct installation of fluoroalkyl groups onto aromatic molecules still represents a challenging and highly demanding synthetic task. Herein, a simple trifluoroethylation process that relies on the palladium-catalyzed C-H activation of aromatic compounds is described. With the utilization of a highly active trifluoroethyl(mesityl)iodonium salt, the developed catalytic method enables the first highly efficient and selective trifluoroethylation of aromatic compounds. The robust catalytic procedure provides the desired products in up to 95 % yield at 25 °C in 1.5 to 3 hours and tolerates a broad range of functional groups. The utilization of hypervalent reagents opens new synthetic possibilities for direct alkylations and fluoroalkylations in the field of transition-metal-catalyzed C-H activation.

  15. 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.

  16. Development of Safe and Scalable Continuous-Flow Methods for Palladium-Catalyzed Aerobic Oxidation Reactions†

    PubMed Central

    Ye, Xuan; Diao, Tianning

    2010-01-01

    Summary The synthetic scope and utility of Pd-catalyzed aerobic oxidation reactions has advanced significantly over the past decade, and these reactions have potential to address important green-chemistry challenges in the pharmaceutical industry. This potential has been unrealized, however, because safety concerns and process constraints hinder large-scale applications of this chemistry. These limitations are addressed by the development of a continuous-flow tube reactor, which has been demonstrated on several scales in the aerobic oxidation of alcohols. Use of a dilute oxygen gas source (8% O2 in N2) ensures that the oxygen/organic mixture never enters the explosive regime, and efficient gas-liquid mixing in the reactor minimizes decomposition of the homogeneous catalyst into inactive Pd metal. These results provide the basis for large-scale implementation of palladium-catalyzed (and other) aerobic oxidation reactions for pharmaceutical synthesis. PMID:20694169

  17. Synthesis of triazafluoranthenones via silver(I)-mediated nonoxidative and oxidative intramolecular palladium-catalyzed cyclizations.

    PubMed

    Koutentis, Panayiotis A; Loizou, Georgia; Lo Re, Daniele

    2011-07-15

    Silver(I) fluoride (AgF)-mediated intramolecular nonoxidative and oxidative palladium-catalyzed cyclizations of 1,3-diphenyl- and 8-iodo-1,3-diphenylbenzo[e][1,2,4]triazin-7(1H)-ones 6a (R = H) and 7a (R = I) afford a new 'alkaloid like' ring system 2-phenyl-6H-[1,2,4]triazino[5,6,1-jk]carbazol-6-one 8a (triazafluoranthenone) in 86 and 100% yields, respectively. Furthermore, these cyclization protocols were used to prepare triazafluoranthenone analogues 8b-e bearing dialkylamino, methoxy, and phenylsulfanyl substituents at C-5, which were also independently synthesized from triazafluoranthenone 8a by regioselective nucleophilic addition. Similar AgF-mediated intramolecular nonoxidative and oxidative palladium-catalyzed cyclizations of 8,10-dihydro-1-iodo-10-phenylphenazin-2(7H)-ones 13 gave the new 'alkaloid like' ring system 8H-indolo[1,2,3-mn]phenazin-8-one 14 in 80 and 18% yields, respectively.

  18. Enantioselective Aminomethylamination of Conjugated Dienes with Aminals Enabled by Chiral Palladium Complex-Catalyzed C-N Bond Activation.

    PubMed

    Liu, Yang; Xie, Yinjun; Wang, Hongli; Huang, Hanmin

    2016-04-06

    A novel highly enantioselective aminomethylamination of conjugated dienes with aminals catalyzed by a chiral palladium complex ligated with BINOL-derived chiral diphosphinite has been successfully developed. This reaction proceeds via a Pd-catalyzed cascade C-N bond activation, aminomethylation, and asymmetric allylic amination reaction under mild reaction conditions, providing a unique and efficient strategy for the synthesis of enantiomerically pure allylic 1,3-diamines.

  19. 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.

  20. 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.

  1. An efficient method for the preparation of tertiary esters by palladium-catalyzed alkoxycarbonylation of aryl bromides.

    PubMed

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

    2012-01-06

    The palladium-catalyzed alkoxycarbonylation of aryl bromides is described for the efficient preparation of tertiary esters. The protocol proved compatible with a wide variety of functionalized (hetero)aromatic bromides, as well as several different sterically hindered tertiary alcohols, affording the alkoxycarbonylated products in high yields. Finally, the formation of aromatic trityl esters is discussed. © 2011 American Chemical Society

  2. Direct palladium-catalyzed arylations of aryl bromides with 2/9-substituted pyrimido[5,4-b]indolizines.

    PubMed

    Jiang, Min; Li, Ting; Meng, Linghua; Yang, Chunhao; Xie, Yuyuan; Ding, Jian

    2009-01-01

    C-5 arylated 2/9-substituted pyrimido[5,4-b]indolizines were synthesized via palladium-catalyzed direct arylation. A variety of substituents on both pyrimido[5,4-b]indolizines and aryl/heteroaryl bromides are tolerated, providing rapid access to substituted pyrimido[5,4-b]indolizines in good to excellent yields.

  3. Enantioselective palladium-catalyzed arylation of N-tosylarylimines with arylboronic acids using a chiral 2,2'-bipyridine ligand.

    PubMed

    Gao, Xiang; Wu, Bo; Yan, Zhong; Zhou, Yong-Gui

    2016-01-07

    With the aid of an axially chiral 2,2'-bipyridine ligand, we have successfully developed a palladium-catalyzed method for the enantioselective arylation of N-tosylarylimines, furnishing the chiral diarylmethamines with high yields and enantioselectivities under very mild conditions. An exogenous base was avoided and imine hydrolysis was inhibited in this transformation.

  4. 2-Substituted 3-arylindoles through palladium-catalyzed arylative cyclization of 2-alkynyltrifluoroacetanilides with arylboronic acids under oxidative conditions.

    PubMed

    Arcadi, Antonio; Cacchi, Sandro; Fabrizi, Giancarlo; Goggiamani, Antonella; Iazzetti, Antonia; Marinelli, Fabio

    2013-01-28

    Free NH 2-substituted 3-arylindoles have been prepared usually in good to high yields through the palladium-catalyzed reaction of readily available 2-alkynyltrifluoroacetanilides with arylboronic acids under oxidative conditions. The reaction tolerates a variety of useful functional groups both in the arylboronic acid and in the alkyne, including chloro, formyl, and ester groups.

  5. Synthesis of 3-acylindoles by palladium-catalyzed acylation of free (N-H) indoles with nitriles.

    PubMed

    Jiang, Tao-Shan; Wang, Guan-Wu

    2013-02-15

    An efficient palladium-catalyzed synthesis of 3-acylindoles using free (N-H) indoles and nitriles has been developed. The acylation reaction proceeded well under the Pd(OAc)(2)/2,2'-bipyridine system and with D-(+)-camphorsulfonic acid as the additive. A possible mechanism involving carbopalladation of nitriles and subsequent hydrolysis of ketimines is proposed.

  6. Palladium-catalyzed oxidative amination of alkenes: improved catalyst reoxidation enables the use of alkene as the limiting reagent.

    PubMed

    Rogers, Michelle M; Kotov, Vasily; Chatwichien, Jaruwan; Stahl, Shannon S

    2007-10-11

    Palladium-catalyzed methods for intermolecular aerobic oxidative amination of alkenes have been identified that are compatible with the use of alkene as the limiting reagent. These procedures, which enhance the utility of this reaction with alkenes that are not commercially available, are demonstrated with substrates bearing dialkyl ether, carboxyester, epoxide, and silyl ether groups.

  7. Enantioselective Construction of Acyclic Quaternary Carbon Stereocenters: Palladium-Catalyzed Decarboxylative Allylic Alkylation of Fully Substituted Amide Enolates.

    PubMed

    Starkov, Pavel; Moore, Jared T; Duquette, Douglas C; Stoltz, Brian M; Marek, Ilan

    2017-07-19

    We report a divergent and modular protocol for the preparation of acyclic molecular frameworks containing newly created quaternary carbon stereocenters. Central to this approach is a sequence composed of a (1) regioselective and -retentive preparation of allyloxycarbonyl-trapped fully substituted stereodefined amide enolates and of a (2) enantioselective palladium-catalyzed decarboxylative allylic alkylation reaction using a novel bisphosphine ligand.

  8. Formal synthesis of nitidine and NK109 via palladium-catalyzed domino direct arylation/N-arylation of aryl triflates.

    PubMed

    Blanchot, Mathieu; Candito, David A; Larnaud, Florent; Lautens, Mark

    2011-03-18

    The use of aryl triflates as reaction partners in a palladium-catalyzed domino direct arylation/N-arylation provides a great advantage due to the availability of starting materials. Furthermore, it allows expedient access to biologically interesting benzo[c]phenanthridine alkaloids.

  9. Synthesis of 3-aryl-8-oxo-5,6,7,8-tetrahydroindolizines via a palladium-catalyzed arylation and heteroarylation.

    PubMed

    Gracia, Stéphanie; Cazorla, Clément; Métay, Estelle; Pellet-Rostaing, Stéphane; Lemaire, Marc

    2009-04-17

    A selective palladium-catalyzed arylation and heteroarylation of 8-oxo-5,6,7,8-tetrahydroindolizines has been developed. Mechanistic studies assume an electrophilic substitution pathway for this transformation. This method provides an efficient one-step synthesis of 3-aryl-8-oxo-5,6,7,8-tetrahydroindolizines.

  10. Eco-friendly solvents for palladium-catalyzed desulfitative C-H bond arylation of heteroarenes.

    PubMed

    Hfaiedh, Anoir; Yuan, Kedong; Ben Ammar, Hamed; Ben Hassine, Bechir; Soulé, Jean-François; Doucet, Henri

    2015-05-22

    Herein, we report the Pd-catalyzed regioselective direct arylation of heteroarenes in which benzenesulfonyl chlorides are used as coupling partners through a desulfitative cross-coupling that can be performed in diethyl carbonate (DEC) or cyclopentyl methyl ether (CPME) as green and renewable solvents or even in neat conditions instead of dioxane or dimethylacetamide (DMA). Under these solvent conditions, the reaction proceeds with a wide range of heteroarenes. C2- or C5-arylated products were obtained with furan and pyrrole derivatives. Benzofuran was also arylated regioselectively at the C2-position, whereas the reaction proceeds selectively at the C3- or C4-positions if thiophenes and benzothiophenes are used. Moreover, in some cases, especially with 1-methylindole, solvent-free conditions afforded better regioselectivities and/or yields than the reaction performed in the presence of solvents. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Chemoselective Palladium-Catalyzed Deprotonative Arylation/[1,2]-Wittig Rearrangement of Pyridylmethyl Ethers

    PubMed Central

    Gao, Feng; Kim, Byeong-Seon

    2015-01-01

    Control of chemoselectivity is one of the most challenging problems facing chemists and is particularly important in the synthesis of bioactive compounds and medications. Herein, the first highly chemoselective tandem C(sp3)–H arylation/[1,2]-Wittig rearrangement of pyridylmethyl ethers is presented. The efficient and operationally simple protocols enable generation of either arylation products or tandem arylation/[1,2]-Wittig rearrangement products with remarkable selectivity and good to excellent yields (60–99%). Choice of base, solvent, and reaction temperature play a pivotal role in tuning the reactivity of intermediates and controlling the relative rates of competing processes. The novel arylation step is catalyzed by a Pd(OAc)2/NIXANTPHOS-based system via a deprotonative cross-coupling process. The method provides rapid access to skeletally diverse aryl(pyridyl)methanol core structures, which are central components of several medications. PMID:27014434

  12. Of the ortho effect in palladium/norbornene-catalyzed reactions: a theoretical investigation.

    PubMed

    Maestri, Giovanni; Motti, Elena; Della Ca', Nicola; Malacria, Max; Derat, Etienne; Catellani, Marta

    2011-06-08

    Mechanistic questions concerning palladium and norbornene catalyzed aryl-aryl coupling reactions are treated in this paper: how aryl halides react with the intermediate palladacycles, formed by interaction of the two catalysts with an aryl halide, and what is the rational explanation of the "ortho effect" (caused by an ortho substituent in the starting aryl halide), which leads to aryl-aryl coupling with a second molecule of aryl halide rather than to aryl-norbornyl coupling. Two possible pathways have been proposed, one involving aryl halide oxidative addition to the palladacycle, the other passing through a palladium(II) transmetalation, also involving the palladacycle, as previously proposed by Cardenas and Echavarren. Our DFT calculations using M06 show that, in palladium-catalyzed reaction of aryl halides, not containing ortho substituents, and norbornene, the intermediate palladacycle formed has a good probability to undergo transmetalation, energetically favored over the oxidative addition leading to Pd(IV). The unselective sp(2)-sp(2) and sp(2)-sp(3) coupling, experimentally observed in this case, can be explained in the framework of the transmetalation pathway since the energetic difference between aryl attack onto the aryl or norbornyl carbon of the palladacycle intermediate is quite small. On the other hand, according to the experimentally observed "ortho effect", selective aryl-aryl coupling only occurs in the reactions of ortho-substituted metallacycles. The present work offers the first possible rationalization of this finding. These in situ formed palladacycles containing an ortho substituent could more easily undergo oxidative addition of an aryl halide rather than reductive elimination from the transmetalation intermediate as a result of a steric clash in the transition state of the latter. The now energetically accessible Pd(IV) intermediate, featuring a Y-distorted trigonal bipyramidal structure, can account for the reported selective aryl

  13. Ruthenium-catalyzed cross-coupling of tertiary propargyl alcohols with omega-alkynenitriles: a regio- and stereoselective surrogate for an aldol condensation.

    PubMed

    Trost, Barry M; Maulide, Nuno; Rudd, Michael T

    2009-01-21

    A novel catalytic alkyne cross-coupling reaction is reported which connects tertiary propargyl alcohols with omega-alkynylnitriles with perfect atom economy. This remarkable process generates highly functionalized, stereodefined dienones that are formal aldol products in a single step. Moreover, the specificity of the cyano substituent for this reaction demonstrates the unique and somewhat underappreciated properties of that functional group.

  14. Electron-Poor, Fluoro-Containing Arylboronic Acids as Efficient Coupling Partners for Bis(1,5-cyclooctadiene)nickel(0)/Tricyclohexylphosphine-Catalyzed Cross-Coupling Reactions of Aryl Arenesulfonates.

    PubMed

    Chen, Wen-Bo; Xing, Chun-Hui; Dong, Jie; Hu, Qiao-Sheng

    2016-06-30

    The use of electron-poor, fluoro-containing arylboronic acids as general coupling partners for nickel(0) /tricyclohexylphosphine-catalyzed cross-coupling of aryl arenesulfonates is described. Electron-poor fluoro-containing arylboronic acids were found to react, faster than electron-rich/neutral arylboronic acids, with (4-methoxyphenyl)(4-methylbenzenesulfonato-κO)bis(tricyclohexylphosphine)nickel. Bis(1,5-cyclooctadiene)nickel(0)/tricyclohexylphosphine, (4-methoxyphenyl)(4-methylbenzenesulfonato-κO)bis(tricyclohexylpho sphine)nickel and bis(tricyclohexylphosphine)nickel (II) bromide were all found to be efficient catalysts/catalyst precursors.

  15. 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

  16. Cross-coupling reactions of aryl pivalates with boronic acids.

    PubMed

    Quasdorf, Kyle W; Tian, Xia; Garg, Neil K

    2008-11-05

    The first cross-coupling of acylated phenol derivatives has been achieved. In the presence of an air-stable Ni(II) complex, readily accessible aryl pivalates participate in the Suzuki-Miyaura coupling with arylboronic acids. The process is tolerant of considerable variation in each of the cross-coupling components. In addition, a one-pot acylation/cross-coupling sequence has been developed. The potential to utilize an aryl pivalate as a directing group has also been demonstrated, along with the ability to sequentially cross-couple an aryl bromide followed by an aryl pivalate, using palladium and nickel catalysis, respectively.

  17. [Novel access to indazoles based on palladium-catalyzed amination chemistry].

    PubMed

    Inamoto, Kiyofumi

    2008-07-01

    Two efficient methods to construct the indazole nucleus have been developed, both of which utilize palladium-catalyzed intramolecular carbon-nitrogen bond formation. One is based on intramolecular Buchwald-Hartwig amination reaction of 2-halobenzophenone tosylhydrazones. The catalyst system we developed for this reaction allows the cyclization to proceed under very mild conditions and thus could be applied to a wide range of substrates with acid- or base-sensitive functional groups. Furthermore, this methodology could be applied for the construction of benzoisoxazole ring system. In addition, catalytic C-H activation with palladium followed by intramolecular amination of benzophenone tosylhydrazones was also accomplished with the aid of the catalyst system such as Pd(OAc)(2)/Cu(OAc)(2)/AgOCOCF(3), which gave another route to indazoles. Using this combination, indazoles with various functional groups could be obtained in good to high yields, especially in the case of substrates having electron donating group such as methoxy group on benzene ring. Interesting chemo- and regioselectivity were also observed in this reaction.

  18. 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

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

    NASA Astrophysics Data System (ADS)

    Müller, Thomas J. J.

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

  20. 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

  1. Palladium-Catalyzed Trifluoromethylation of (Hetero)Arenes with CF3 Br.

    PubMed

    Natte, Kishore; Jagadeesh, Rajenahally V; He, Lin; Rabeah, Jabor; Chen, Jianbin; Taeschler, Christoph; Ellinger, Stefan; Zaragoza, Florencio; Neumann, Helfried; Brückner, Angelika; Beller, Matthias

    2016-02-18

    The CF3 group is an omnipresent motif found in many pharmaceuticals, agrochemicals, catalysts, materials, and industrial chemicals. Despite well-established trifluoromethylation methodologies, the straightforward and selective introduction of such groups into (hetero)arenes using available and less expensive sources is still a major challenge. In this regard, the selective synthesis of various trifluoromethyl-substituted (hetero)arenes by palladium-catalyzed C-H functionalization is herein reported. This novel methodology proceeds under comparably mild reaction conditions with good regio- and chemoselectivity. As examples, trifluoromethylations of biologically important molecules, such as melatonin, theophylline, caffeine, and pentoxifylline, are showcased. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Palladium(0)-catalyzed amination, Stille coupling, and Suzuki coupling of electron-deficient aryl fluorides.

    PubMed

    Kim, Young Mi; Yu, Shu

    2003-02-19

    The amination of 2-fluoronitrobenzene was Pd(0) catalyzed at 65 degrees C in DMF, and the effectiveness of the catalysis was ligand-dependent. Among the five catalyst systems investigated, Pd(PPh3)4 was the most effective catalyst. The control experiments revealed that Pd(OAc)2 or PPh3 was not responsible for the catalysis. 4-Fluoro-3-nitro-benzonitrile and 4-fluoro-3-nitro-benzaldehyde also underwent Stille coupling and Suzuki coupling in the presence of Pd(PPh3)4, and the reactions afforded the coupling products in 28-86% yields. The control experiments showed no sign of reaction in the absence of palladium. These results were in agreement with the oxidative addition/reductive elimination pathway, where the oxidative addition could conceivably proceed via the SNAr mechanism.

  3. Palladium-catalyzed asymmetric allylic amination of racemic butadiene monoxide with isatin derivatives.

    PubMed

    Li, Gen; Feng, Xiangqing; Du, Haifeng

    2015-05-28

    Isatins and their derivatives are important functional moities and building blocks in pharmaceutical and synthetic chemistry. Numerous enantioselective transformations at the C-3 carbonyl group have been well developed. However, the asymmetric substitution reaction with isatins and their derivatives as nucleophiles based on the free N-H groups has been less studied due to the relatively weaker nucleophilicity resulting from the two electron-withdrawing carbonyl groups. In this paper, a palladium-catalyzed asymmetric allylic amination of racemic butadiene monoxide with isatin derivatives using a chiral phosphoramidite olefin hybrid ligand has been successfully developed under mild conditions. A variety of chiral amino alcohols were afforded in 55-87% yields with 10/1->20/1 regioselectivity ratios and 80-97% ees.

  4. 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.

  5. Enantioselective amine α-functionalization via palladium catalyzed C–H arylation of thioamides

    PubMed Central

    Jain, Pankaj; Verma, Pritha; Xia, Guoqin; Yu, Jin-Quan

    2016-01-01

    Saturated aza-heterocycles are highly privileged building blocks that are commonly encountered in bioactive compounds and approved therapeutic agents. These N-heterocycles are also incorporated as chiral auxiliaries and ligands in asymmetric synthesis. As such, development of methods to functionalize the α-methylene C–H bonds of these systems enantioselectively is of great importance, especially in drug discovery. Currently, enantioselective lithiation with (–)-sparteine followed by Pd(0) catalyzed cross coupling to prepare α-arylated amines is largely limited to pyrrolidines. Here we report a Pd(II)-catalyzed enantioselective α-C–H coupling of a wide range of amines, including ethyl amines, azetidines, pyrrolidines, piperidines, azepanes, indolines, and tetrahydroisoquinolines. Chiral phosphoric acids are demonstrated as effective anionic ligands for the enantioselective coupling of methylene C–H bonds with aryl boronic acids. This catalytic reaction not only affords high enantioselectivities, but also provides exclusive regioselectivity in the presence of two methylene groups in different steric environments. PMID:28282045

  6. Cross-coupling of aromatic bromides with allylic silanolate salts.

    PubMed

    Denmark, Scott E; Werner, Nathan S

    2008-12-03

    The sodium salts of allyldimethylsilanol and 2-butenyldimethylsilanol undergo palladium-catalyzed cross-coupling with a wide variety of aryl bromides to afford allylated and crotylated arenes. The coupling of both silanolates required extensive optimization to deliver the expected products in high yields. The reaction of the allyldimethylsilanolate takes place at 85 degrees C in 1,2-dimethoxyethane with allylpalladium chloride dimer (2.5 mol %) to afford 73-95% yields of the allylation products. Both electron-rich and sterically hindered bromides reacted smoothly, whereas electron-poor bromides cross-coupled in poor yield because of a secondary isomerization to the 1-propenyl isomer (and subsequent polymerization). The 2-butenyldimethylsilanolate (E/Z, 80:20) required additional optimization to maximize the formation of the branched (gamma-substitution) product. A remarkable influence of added alkenes (dibenzylideneacetone and norbornadiene) led to good selectivities for electron-rich and electron-poor bromides in 40-83% yields. However, bromides containing coordinating groups (particularly in the ortho position) gave lower, and in one case even reversed, selectivity. Configurationally homogeneous (E)-silanolates gave slightly higher gamma-selectivity than the pure (Z)-silanolates. A unified mechanistic picture involving initial gamma-transmetalation followed by direct reductive elimination or sigma-pi isomerization can rationalize all of the observed trends.

  7. Polar, non-coordinating ionic liquids as solvents for the alternating copolymerization of styrene and CO catalyzed by cationic palladium catalysts.

    PubMed

    Klingshirn, Marc A; Broker, Grant A; Holbrey, John D; Shaughnessy, Kevin H; Rogers, Robin D

    2002-07-07

    The palladium-catalyzed copolymerization of styrene and CO in an ionic liquid solvent, 1-hexylpyridinium bis(trifluoromethanesulfonyl)imide, gave improved yields and increased molecular weights compared to polymerizations run in methanol.

  8. Dibenzo[a,c]carbazoles from 2-(2-bromoaryl)-3-arylindoles via a palladium-catalyzed intramolecular C-H functionalization/C-C bond formation process.

    PubMed

    Cacchi, Sandro; Fabrizi, Giancarlo; Goggiamani, Antonella; Iazzetti, Antonia

    2012-12-14

    The palladium-catalyzed cyclization of 2-(2-bromoaryl)-3-arylindoles provides a new versatile approach to dibenzo[a,c]carbazoles. The reaction tolerates a variety of useful substituents including chloro, nitro, ether, cyano, keto, and ester groups.

  9. A convergent synthesis of the C1-C16 segment of goniodomin A via palladium-catalyzed organostannane-thioester coupling.

    PubMed

    Fuwa, Haruhiko; Nakajima, Motohiro; Shi, Jinglu; Takeda, Yoshiyuki; Saito, Tomoyuki; Sasaki, Makoto

    2011-03-04

    A convergent synthesis of the C1-C16 segment of goniodomin A, an actin-targeting marine polyether macrolide natural product, has been achieved via a 2-fold application of palladium-catalyzed organostannane-thioester coupling.

  10. Palladium(II)-catalyzed coupling reactions with a chelating vinyl ether and arylboronic acids: a new Heck/Suzuki domino diarylation reaction.

    PubMed

    Trejos, Alejandro; Fardost, Ashkan; Yahiaoui, Samir; Larhed, Mats

    2009-12-28

    A mild and novel palladium(II)-catalyzed domino Heck/Suzuki alpha,beta-diarylation-reduction of a dimethylaminoethyl substituted chelating vinyl ether was developed by using electron-rich arylboronic acids in combination with p-benzoquinone. Based on the preparative results, a catalytic cycle is proposed. Further, highly regioselective palladium(II)-catalyzed alpha- or beta-monoarylation of the chelating vinyl ether was achieved using either a bidentate ligand or by employing ligand-less conditions.

  11. Palladium(II)-catalyzed desulfitative synthesis of aryl ketones from sodium arylsulfinates and nitriles: scope, limitations, and mechanistic studies.

    PubMed

    Skillinghaug, Bobo; Sköld, Christian; Rydfjord, Jonas; Svensson, Fredrik; Behrends, Malte; Sävmarker, Jonas; Sjöberg, Per J R; Larhed, Mats

    2014-12-19

    A fast and efficient protocol for the palladium(II)-catalyzed production of aryl ketones from sodium arylsulfinates and various organic nitriles under controlled microwave irradiation has been developed. The wide scope of the reaction has been demonstrated by combining 14 sodium arylsulfinates and 21 nitriles to give 55 examples of aryl ketones. One additional example illustrated that, through the choice of the nitrile reactant, benzofurans are also accessible. The reaction mechanism was investigated by electrospray ionization mass spectrometry and DFT calculations. The desulfitative synthesis of aryl ketones from nitriles was also compared to the corresponding transformation starting from benzoic acids. Comparison of the energy profiles indicates that the free energy requirement for decarboxylation of 2,6-dimethoxybenzoic acid and especially benzoic acid is higher than the corresponding desulfitative process for generating the key aryl palladium intermediate. The palladium(II) intermediates detected by ESI-MS and the DFT calculations provide a detailed understanding of the catalytic cycle.

  12. A Highly Active Catalyst for Pd-Catalyzed Amination Reactions: Cross-Coupling Reactions Using Aryl Mesylates and the Highly Selective Monoarylation of Primary Amines Using Aryl Chlorides

    PubMed Central

    Fors, Brett P.; Watson, Donald A.; Biscoe, Mark R.; Buchwald, Stephen L.

    2009-01-01

    A catalyst system based on a new biarylmonophosphine ligand (BrettPhos) that shows excellent reactivity for C–N cross-coupling reactions is reported. This catalyst system enables the use of aryl mesylates as a coupling partner in C–N bond-forming reactions. Additionally, the use of BrettPhos permits the highly selective monoarylation of an array of primary aliphatic amines and anilines at low catalyst loadings and with fast reaction times, including the first monoarylation of methylamine. Lastly, oxidative addition complexes of BrettPhos are included, which provide insight into the origin of reactivity for this system. PMID:18798626

  13. 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.

  14. 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.

  15. Combinatorial synthesis of RGD model cyclic peptides utilizing a palladium-catalyzed carbonylative macrolactamization on a polymer support.

    PubMed

    Kamioka, Seiji; Shimazu, Sayaka; Doi, Takayuki; Takahashi, Takashi

    2008-01-01

    A combinatorial synthesis of 24-member RGD models was accomplished on polymer-support. Ortho-, meta-, and para-iodobenzylamines loaded on an aldehyde linker by reductive amination were coupled with RGD sequences and various omega-amino acids by a split-and-pool method. Palladium-catalyzed carbonylative macrolactamization of the polymer-supported cyclization precursors, followed by acid cleavage, provided conformationally restricted RGD model cyclic peptides.

  16. 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. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Palladium-catalyzed arylation of ketone enolates: an expeditious entry to tamoxifen-related 1,2,2-triarylethanones.

    PubMed

    Churruca, Fátima; SanMartin, Raul; Tellitu, Imanol; Domínguez, Esther

    2002-05-02

    [reaction: see text]. After a rigorous study on the effect of several catalytic systems, a simple, high yielding procedure for the preparation of 1,2,2-triarylethanones, skeletal analogues of tamoxifen, is presented. Apart from the economic and environmental advantages involved, this palladium-catalyzed arylation of deoxybenzoin enolates features a lack of ortho-arylation side reactions. In addition, an alternative approach from acetophenones to the target triarylethanone system is also announced.

  18. An approach to the synthesis of dimeric resveratrol natural products via a palladium-catalyzed domino reaction

    PubMed Central

    Jeffrey, Jenna L.; Sarpong, Richmond

    2009-01-01

    A route for the rapid assembly of the carbon framework of several resveratrol natural products is presented. A palladium-catalyzed domino reaction of bromostilbene derivative 6 and tolane 7, involving two sequential Heck coupling reactions, provides access to the benzofulvene-based core of various resveratrol-derived natural products. The carbon skeleton of pallidol and its congeners is achieved by a Lewis acid-induced Nazarov-type oxidative cyclization of 9. PMID:20161322

  19. Synthesis of Highly Functionalized Triarylbismuthines by Functional Group Manipulation and Use in Palladium- and Copper-Catalyzed Arylation Reactions.

    PubMed

    Hébert, Martin; Petiot, Pauline; Benoit, Emeline; Dansereau, Julien; Ahmad, Tabinda; Le Roch, Adrien; Ottenwaelder, Xavier; Gagnon, Alexandre

    2016-07-01

    Organobismuthines are an attractive class of organometallic reagents that can be accessed from inexpensive and nontoxic bismuth salts. Triarylbismuthines are particularly interesting due to their air and moisture stability and high functional group tolerance. We report herein a detailed study on the preparation of highly functionalized triarylbismuth reagents by triple functional group manipulation and their use in palladium- and copper-catalyzed C-, N-, and O-arylation reactions.

  20. Palladium-Catalyzed C-2 C-H Heteroarylation of Chiral Oxazolines: Diverse Synthesis of Chiral Oxazoline Ligands.

    PubMed

    Xi, Tuo; Mei, Yuncai; Lu, Zhan

    2015-12-18

    A direct, efficient, and practical protocol to install a chiral oxazoline unit onto aryl/heteroaryl rings via palladium-catalyzed C-H functionalization of 2-positions of oxazolines with a variety of halides using dppe as the ligand has been developed. Various chiral oxazoline ligands could be synthesized, even in a 10-g scale process. This protocol is a good supplement to traditional methods and for diverse synthesis of chiral oxazoline ligands.

  1. Ligand bite angle-dependent palladium-catalyzed cyclization of propargylic carbonates to 2-alkynyl azacycles or cyclic dienamides.

    PubMed

    Daniels, David S B; Jones, Alison S; Thompson, Amber L; Paton, Robert S; Anderson, Edward A

    2014-02-10

    The regioselectivity of the palladium-catalyzed cyclization of propargylic carbonates with sulfonamide nucleophiles is critically dependent on the bite angle of the bidentate phosphine ligand. Ligands with small bite angles favor attack on the central carbon atom of an allenylpalladium intermediate to afford cyclic dienamide products, whereas the use of those with large bite angles leads to alkynyl azacycles, with high stereoselectivity. A computational analysis of the reaction pathway is also presented.

  2. 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.

  3. Palladium-catalyzed carbonylation reactions of aryl bromides at atmospheric pressure: a general system based on Xantphos.

    PubMed

    Martinelli, Joseph R; Watson, Donald A; Freckmann, Dominique M M; Barder, Timothy E; Buchwald, Stephen L

    2008-09-19

    A method for the Pd-catalyzed carbonylation of aryl bromides has been developed using Xantphos as the ligand. This method is effective for the direct synthesis of Weinreb amides, primary and secondary benzamides, and methyl esters from the corresponding aryl bromides at atmospheric pressure. In addition, a putative catalytic intermediate, (Xanphos)Pd(Br)benzoyl, was prepared and an X-ray crystal structure was obtained revealing an unusual cis-coordination mode of Xantphos in this palladium-acyl complex.

  4. Expanding insight into asymmetric palladium-catalyzed allylic alkylation of N-heterocyclic molecules and cyclic ketones.

    PubMed

    Bennett, Nathan B; Duquette, Douglas C; Kim, Jimin; Liu, Wen-Bo; Marziale, Alexander N; Behenna, Douglas C; Virgil, Scott C; Stoltz, Brian M

    2013-04-02

    Eeny, meeny, miny ... enaminones! Lactams and imides have been shown to consistently provide enantioselectivities substantially higher than other substrate classes previously investigated in the palladium-catalyzed asymmetric decarboxylative allylic alkylation. Several new substrates have been designed to probe the contributions of electronic, steric, and stereoelectronic factors that distinguish the lactam/imide series as superior alkylation substrates (see scheme). These studies culminated in marked improvements on carbocyclic allylic alkylation substrates.

  5. A palladium-catalyzed three-component-coupling strategy for the differential vicinal diarylation of terminal 1,3-dienes.

    PubMed

    Stokes, Benjamin J; Liao, Longyan; de Andrade, Aline Mendes; Wang, Qiaofeng; Sigman, Matthew S

    2014-09-05

    A palladium-catalyzed intermolecular vicinal diarylation of terminal 1,3-dienes using aryldiazonium tetrafluoroborates and arylboronic acids is reported. Using this technology, two different arenes are regioselectively introduced in a vicinal fashion across the terminal alkene of a variety of terminal 1,3-dienes at ambient temperature. Through the action of a chiral bicyclo[2.2.2]octadienyl ligand at -20 °C, good enantioselectivity has also been achieved.

  6. A novel synthesis of 2-aryl-2H-indazoles via a palladium-catalyzed intramolecular amination reaction.

    PubMed

    Song, J J; Yee, N K

    2000-02-24

    [reaction: see text] A variety of 2-aryl-2H-indazoles were synthesized by the palladium-catalyzed intramolecular amination of the corresponding N-aryl-N(o-bromobenzyl)hydrazines. Of several sets of reaction conditions surveyed, the combination of Pd(OAc)2/dppf/tBuONa gave the best results. This method applies to a wide scope of substrates containing electron-donating and electron-withdrawing substituents.

  7. 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

  8. 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

    2014-07-07

    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. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. 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

  10. 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

  11. Mechanism, reactivity, and selectivity in palladium-catalyzed redox-relay Heck arylations of alkenyl alcohols.

    PubMed

    Xu, Liping; Hilton, Margaret J; Zhang, Xinhao; Norrby, Per-Ola; Wu, Yun-Dong; Sigman, Matthew S; Wiest, Olaf

    2014-02-05

    The enantioselective Pd-catalyzed redox-relay Heck arylation of acyclic alkenyl alcohols allows access to various useful chiral building blocks from simple olefinic substrates. Mechanistically, after the initial migratory insertion, a succession of β-hydride elimination and migratory insertion steps yields a saturated carbonyl product instead of the more general Heck product, an unsaturated alcohol. Here, we investigate the reaction mechanism, including the relay function, yielding the final carbonyl group transformation. M06 calculations predict a ΔΔG(‡) of 1 kcal/mol for the site selectivity and 2.5 kcal/mol for the enantioselectivity, in quantitative agreement with experimental results. The site selectivity is controlled by a remote electronic effect, where the developing polarization of the alkene in the migratory insertion transition state is stabilized by the C-O dipole of the alcohol moiety. The enantioselectivity is controlled by steric repulsion between the oxazoline substituent and the alcohol-bearing alkene substituent. The relay efficiency is due to an unusually smooth potential energy surface without high barriers, where the hydroxyalkyl-palladium species acts as a thermodynamic sink, driving the reaction toward the carbonyl product. Computational predictions of the relative reactivity and selectivity of the double bond isomers are validated experimentally.

  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. Possible intermediates of Cu(phen)-catalyzed C-O cross-coupling of phenol with an aryl bromide by in situ ESI-MS and EPR studies.

    PubMed

    Chen, Hong-Jie; Hsu, I-Jui; Tseng, Mei-Chun; Shyu, Shin-Guang

    2014-08-07

    The C-O coupling reaction between 2,4-dimethylphenol and 4-bromotoluene catalyzed by the CuI/K2CO3/phen system can be inhibited by the radical scavenger cumene. Complexes [Cu(i)(phen)(1-(2,4-dimethylphenoxy)-4-methylbenzene)](+) (denoted as A), {H[Cu(i)(phen)(2,4-dimethylphenoxy)]}(+) and [Cu(i)(2,4-dimethylphenoxy)2](-) (denoted as B) were observed by in situ electrospray ionization mass spectrometry (ESI-MS) analysis of the copper(i)-catalyzed C-O coupling reaction under the catalytic reaction conditions indicating that they could be intermediates in the reaction. The in situ EPR study of the reaction solution detected the Cu(ii) species with a fitted g value of 2.188. A catalytic cycle with a single electron transfer (SET) step was proposed based on these observations.

  14. 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

  15. Palladium(II)-catalyzed enantioselective C(sp³)-H activation using a chiral hydroxamic acid ligand.

    PubMed

    Xiao, Kai-Jiong; Lin, David W; Miura, Motofumi; Zhu, Ru-Yi; Gong, Wei; Wasa, Masayuki; Yu, Jin-Quan

    2014-06-04

    An enantioselective method for Pd(II)-catalyzed cross-coupling of methylene β-C(sp(3))-H bonds in cyclobutanecarboxylic acid derivatives with arylboron reagents is described. High yields and enantioselectivities were achieved through the development of chiral mono-N-protected α-amino-O-methylhydroxamic acid (MPAHA) ligands, which form a chiral complex with the Pd(II) center. This reaction provides an alternative approach to the enantioselective synthesis of cyclobutanecarboxylates containing α-chiral quaternary stereocenters. This new class of chiral catalysts also show promises for enantioselective β-C(sp(3))-H activation of acyclic amides.

  16. New insights on the mechanism of palladium-catalyzed hydrolysis of sodium borohydride from 11B NMR measurements.

    PubMed

    Guella, G; Zanchetta, C; Patton, B; Miotello, A

    2006-08-31

    To gain insight on the mechanistic aspects of the palladium-catalyzed hydrolysis of NaBH(4) in alkaline media, the kinetics of the reaction has been investigated by (11)B NMR (nuclear magnetic resonance) measurements taken at different times during the reaction course. Working with BH(4)(-) concentration in the range 0.05-0.1 M and with a [substrate]/[catalyst] molar ratio of 0.03-0.11, hydrolysis has been found to follow a first-order kinetic dependence from concentration of both the substrate and the catalyst (Pd/C 10 wt %). We followed the reaction of NaBH(4) and its perdeuterated analogue NaBD(4) in H(2)O, in D(2)O and H(2)O/D(2)O mixtures. When the process was carried out in D(2)O, deuterium incorporation in BH(4)(-) afforded BH(4)(-)(n)D(n)(-) (n = 1, 2, 3, 4) species, and a competition between hydrolysis and hydrogen/deuterium exchange processes was observed. By fitting the kinetics NMR data by nonlinear least-squares regression techniques, the rate constants of the elementary steps involved in the palladium-catalyzed borohydride hydrolysis have been evaluated. Such a regression analysis was performed on a reaction scheme wherein the starting reactant BH(4)(-) is allowed both to reversibly exchange hydrogen with deuterium atoms of D(2)O and to irreversibly hydrolyze into borohydroxy species B(OD)(4)(-). In contrast to acid-catalyzed hydrolysis of sodium borohydride, our results indicate that in the palladium-catalyzed process the rate constants of the exchange processes are higher than those of the corresponding hydrolysis reactions.

  17. 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.

  18. Non-innocent additives in a palladium(II)-catalyzed C-H bond activation reaction: insights into multimetallic active catalysts.

    PubMed

    Anand, Megha; Sunoj, Raghavan B; Schaefer, Henry F

    2014-04-16

    The role of a widely employed additive (AgOAc) in a palladium acetate-catalyzed ortho-C-H bond activation reaction has been examined using the M06 density functional theory. A new hetero-bimetallic Pd-(μ-OAc)3-Ag is identified as the most likely active species. This finding could have far-reaching implications with respect to the notion of the active species in palladium catalysis in the presence of other metal salt additives.

  19. 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

    2015-11-09

    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.

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

    PubMed

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

    2015-11-02

    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.

  1. Palladium-catalyzed allylation of acidic and less nucleophilic anilines using allylic alcohols directly.

    PubMed

    Hsu, Yi-Chun; Gan, Kim-Hong; Yang, Shyh-Chyun

    2005-10-01

    The direct activation of C-O bonds in allylic alcohols by palladium complexes has been accelerated by carrying out the reactions in the presence of titanium(IV) isoproxide and 4 A molecular sieves. The acidic and less nucleophilic anilines such as diphenylamine, phenothiazine, 4-cyanoaniline, and nitroanilines are efficiently allylated under palladium catalysis using allylic alcohols as allylating reagents.

  2. Palladium-catalyzed decarboxylative, decarbonylative and dehydrogenative C(sp(2))-H acylation at room temperature.

    PubMed

    Hossian, Asik; Manna, Manash Kumar; Manna, Kartic; Jana, Ranjan

    2017-08-09

    Over the past few decades, an impressive array of C-H activation methodology has been developed for organic synthesis. However, due to the inherent inertness of the C-H bonds (e.g. ∼110 kcal mol(-1) for the cleavage of C(aryl)-H bonds) harsh reaction conditions have been realized to overcome high energetic transition states resulting in a limited substrate scope and functional group tolerance. Therefore, the development of mild C-H functionalization protocols is in high demand to exploit the full potential of the C-H activation strategy in the synthesis of a complex molecular framework. Although, electron-rich substrates undergo electrophilic metalation under relatively mild conditions, electron-deficient substrates proceed through a rate-limiting C-H insertion under forcing conditions at high temperature. In addition, a stoichiometric amount of toxic silver salt is frequently used in palladium catalysis to facilitate the C-H activation process which is not acceptable from the environmental and industrial standpoint. We report herein, a Pd(ii)-catalyzed decarboxylative C-H acylation of 2-arylpyridines with α-ketocarboxylic acids under mild conditions. The present protocol does not require stoichiometric silver(i) salts as additives and proceeds smoothly at ambient temperature. A novel decarbonylative C-H acylation reaction has also been accomplished using aryl glyoxals as acyl surrogates. Finally, a practical C-H acylation via a dehydrogenative pathway has been demonstrated using commercially available benzaldehydes and aqueous hydroperoxides. We also disclose that acetonitrile solvent is optimal for the acylation reaction at room temperature and has a prominent role in the reaction outcome. Control experiments suggest that the acylation reaction via decarboxylative, decarbonylative and dehydrogenative proceeds through a radical pathway. Thus we disclose a practical protocol for the sp(2) C-H acylation reaction.

  3. 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.

  4. Palladium-catalyzed arylation of 2H-chromene: a new entry to pyrano[2,3-c]carbazoles.

    PubMed

    Ranjith Reddy, K; Siva Reddy, A; Dhaked, Devendra K; Rasheed, S K; Pathania, Anup Singh; Shankar, Ravi; Malik, Fayaz; Das, Parthasarathi

    2015-09-21

    Pyrano[2,3-c]carbazoles which are biologically valuable and synthetically challenging frameworks are synthesized in high yields over five steps from commercially available resorcinol. Palladium-catalyzed arylation remains a key step in this novel strategy. The versatility of this protocol has been demonstrated by the synthesis of naturally occurring alkaloid clauraila C and 7-methoxyglycomaurin. The anti-proliferative activity of these designed compounds (5a, 5f, and 5l) has been evaluated in a cancer cell line (MOLT-4). The molecular docking study revealed that this pyrano[2,3-c]carbazole class of molecules selectively occupies the colchicine binding site of the tubulin-polymer.

  5. Palladium-catalyzed intramolecular coupling of 2-[(2-pyrrolyl)silyl]aryl triflates through 1,2-silicon migration.

    PubMed

    Mochida, Kenji; Shimizu, Masaki; Hiyama, Tamejiro

    2009-06-24

    Palladium-catalyzed intramolecular direct arylation of 2-[(2-pyrrolyl)silyl]aryl triflates gives 3,2'-silicon-bridged 2-arylindoles and -pyrroles in good to high yields. The reaction proceeds through cleavage of C-OTf, C-Si, and C-H bonds to result in the formation of C-C and C-Si bonds. Various kinds of functional groups such as OMe, CN, Cl, F, and SiMe(3) tolerated the conditions. The new reaction allows synthesis of functionalized Si-bridged 2-arylindoles that emit intense and efficient blue fluorescence in the solid state.

  6. Palladium-catalyzed annulation of diarylamines with olefins through C-H activation: direct access to N-arylindoles.

    PubMed

    Sharma, Upendra; Kancherla, Rajesh; Naveen, Togati; Agasti, Soumitra; Maiti, Debabrata

    2014-10-27

    A palladium-catalyzed dehydrogenative coupling between diarylamines and olefins has been discovered for the synthesis of substituted indoles. This intermolecular annulation approach incorporates readily available olefins for the first time and obviates the need of any additional directing group. An ortho palladation, olefin coordination, and β-migratory insertion sequence has been proposed for the generation of olefinated intermediate, which is found to produce the expected indole moiety. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Synthesis of diarylmethylamines via palladium-catalyzed regioselective arylation of 1,1,3-triaryl-2-azaallyl anions†

    PubMed Central

    Li, Minyan; Yücel, Baris; Adrio, Javier; Bellomo, Ana

    2014-01-01

    Diarylmethylamines are of great interest due to their prevalence in pharmaceutical chemistry. As a result, new methods for their synthesis are in demand. Herein, we report a versatile protocol for the synthesis of diarylmethylamine derivatives involving palladium-catalyzed arylation of in situ generated 2-azaallyl anion intermediates. The 2-azaallyl anions are generated by reversible deprotonation of readily available aldimine and ketimine precursors. Importantly, the arylated aldimine and ketimine products do not undergo isomerization under the reaction conditions. Scale-up of the arylation and hydrolysis of the resulting products to furnish diarylmethylamines were also successfully performed. PMID:25396041

  8. The Development of a Palladium-Catalyzed Tandem Addition/Cyclization for Direct Construction of Indole Skeletons.

    PubMed

    Yu, Shuling; Qi, Linjun; Hu, Kun; Gong, Julin; Cheng, Tianxing; Wang, Qingzong; Chen, Jiuxi; Wu, Huayue

    2017-03-13

    A palladium-catalyzed tandem addition/cyclization of 2-(2-aminoaryl)acetonitriles with arylboronic acids has been developed for the first time, achieving a new strategy for direct construction of indole skeletons. This system shows good functional group tolerance and remarkable chemoselectivity. Especially, the halogen (e.g. bromo and iodo) substituents are amenable for further synthetic elaborations thereby broadening the diversity of the products. Preliminary mechanistic experiments indicate that this transformation involves sequential nucleophilic addition followed by an intramolecular cyclization.

  9. Palladium-Catalyzed Carbonylation Reactions of Aryl Bromides at Atmospheric Pressure: A General System Based on Xantphos

    PubMed Central

    Martinelli, Joseph R.; Watson, Donald A.; Freckmann, Dominique M. M.; Barder, Timothy E.; Buchwald, Stephen L.

    2009-01-01

    A method for the Pd-catalyzed carbonylation of aryl bromides has been developed using Xantphos as the ligand. This method is effective for the direct synthesis of Weinreb amides, 1° and 2° benzamides and methyl esters from the corresponding aryl bromides at atmospheric pressure. In addition, a putative catalytic intermediate, (Xanphos)Pd(Br)benzoyl, was prepared and an X-ray crystal structure was obtained revealing an unusual cis-coordination mode of Xantphos in this palladium-acyl complex. PMID:18720970

  10. Palladium(II)-catalyzed ortho-C-H arylation/alkylation of N-benzoyl α-amino ester derivatives.

    PubMed

    Misal Castro, Luis C; Chatani, Naoto

    2014-04-14

    The palladium-catalyzed arylation/alkylation of ortho-C-H bonds in N-benzoyl α-amino ester derivatives is described. In such a system both the NH-amido and the CO2R groups in the α-amino ester moieties play a role in successful C-H activation/C-C bond formation using iodoaryl coupling partners. A wide variety of functional groups and electron-rich/deficient iodoarenes are tolerated. The yields obtained range from 20 to 95%.

  11. Synthesis of aza-fused isoquinolines through domino cross-aldol condensation and palladium-catalyzed intramolecular direct arylation.

    PubMed

    Dhiman, Shiv; Pericherla, Kasiviswanadharaju; Nandwana, Nitesh K; Kumar, Dalip; Kumar, Anil

    2014-08-15

    A straightforward method has been developed for the synthesis of aroyl-substituted imidazo-/benzimidazo-fused isoquinolines. The cascade reaction proceeds via a cross-aldol condensation of 2-(1H-imidazol-1-yl/benzimidazolyl-1-yl)-1-arylethanones and 2-bromobenzaldehyde followed by palladium-catalyzed intramolecular C-H functionalization. This approach offers a simple and efficient alternative one-pot protocol for the assembly of imidazo/benzimidazo[2,1-a]isoquinolines in moderate to good yields.

  12. Palladium-Catalyzed Oxidative Direct C3- and C7-Alkenylations of Indazoles: Application to the Synthesis of Gamendazole.

    PubMed

    Naas, Mohammed; El Kazzouli, Saïd; Essassi, El Mokhtar; Bousmina, Mosto; Guillaumet, Gérald

    2015-09-04

    The first palladium-catalyzed oxidative alkenylation of (1H)- and (2H)-indazole derivatives with various olefins is described. The use of Pd(OAc)2 as the catalyst and Ag2CO3 as the oxidant promoted the selective C3-monoalkenylation of (1H)-indazoles and (2H)-indazoles, affording the desired products in good yields. An original oxidative C7-alkenylation of 3-substituted (1H)-indazoles was also developed. The oxidative alkenylation of (1H)-indazole was successfully applied to the total synthesis of the drug candidate gamendazole in a step- and atom-economical fashion.

  13. Palladium-Catalyzed Synthesis of 2,3-Disubstituted Benzofurans: An Approach Towards the Synthesis of Deuterium Labeled Compounds

    PubMed Central

    Agasti, Soumitra; Maity, Soham; Szabo, Kalman J; Maiti, Debabrata

    2015-01-01

    Palladium-catalyzed oxidative annulations between phenols and alkenylcarboxylic acids produced a library of benzofuran compounds. Depending on the nature of the substitution of the phenol precursor, either 2,3-dialkylbenzofurans or 2-alkyl-3-methylene-2,3-dihydrobenzofurans can be synthesized with excellent regioselectivity. Reactions between conjugated 5-phenylpenta-2,4-dienoic acids and phenol gave 3-alkylidenedihydrobenzofuran alkaloid motifs while biologically active 7-arylbenzofuran derivatives were prepared by starting from 2-phenylphenols. More interestingly, selective incorporation of deuterium from D2O has been discovered, which offers an attractive one-step method to access deuterated compounds. PMID:26347405

  14. Continuous-Flow Synthesis and Derivatization of Aziridines through Palladium-Catalyzed C(sp(3) )-H Activation.

    PubMed

    Zakrzewski, Jacek; Smalley, Adam P; Kabeshov, Mikhail A; Gaunt, Matthew J; Lapkin, Alexei A

    2016-07-25

    A continuous-flow synthesis of aziridines by palladium-catalyzed C(sp(3) )-H activation is described. The new flow reaction could be combined with an aziridine-ring-opening reaction to give highly functionalized aliphatic amines through a consecutive process. A predictive mechanistic model was developed and used to design the C-H activation flow process and illustrates an approach towards first-principles design based on novel catalytic reactions. © 2016 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

  15. Palladium-catalyzed cyclization/Heck- and cyclization/conjugate-addition-type sequences in the preparation of polysubstituted furans.

    PubMed

    Aurrecoechea, José M; Durana, Aritz; Pérez, Elena

    2008-05-02

    Palladium-catalyzed heterocyclization-coupling sequences have been developed starting from buta-1,2,3-trienyl carbinols and electron-deficient alkenes. Polysubstituted furans are formed where the heterocyclic ring originates from the elements of the butatrienyl carbinol while the electron-deficient olefin is incorporated as a C-3 substituent. In most cases, the reaction proceeds via a Heck-type pathway leading to the efficient formation of 3-vinylfurans. However, couplings with methyl vinyl ketone display a divergent behavior to afford selectively either Heck- or hydroarylation-type products depending on reaction conditions.

  16. Palladium-catalyzed domino C-H/N-H functionalization: an efficient approach to nitrogen-bridged heteroacenes.

    PubMed

    Kamimoto, Natsuyo; Schollmeyer, Dieter; Mitsudo, Koichi; Suga, Seiji; Waldvogel, Siegfried R

    2015-05-26

    Palladium-catalyzed domino C-H/N-H functionalization for the synthesis of novel nitrogen-bridged thienoacenes and 10H-benzo[4,5]thieno[3,2-b]indole derivatives from dihaloarene is reported. This domino sequence consists of initial C-H functionalization of the benzo[b]thiophene moiety, followed by Buchwald-Hartwig coupling. This transformation is also useful for the synthesis of highly π-extended compounds. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Palladium(0)-Catalyzed Benzylic C(sp(3))-H Functionalization for the Concise Synthesis of Heterocycles and Its Applications.

    PubMed

    Tsukano, Chihiro

    2017-01-01

    C-H functionalization reactions involve the activation of otherwise unreactive C-H bonds, and represent atom economical methods for the direct transformation of simple substrates to complex molecules. While transition metal-catalyzed C(sp(2))-H functionalization reactions are regularly used in synthesis, C(sp(3))-H functionalization is rarely applied to the synthesis of complex natural products because of the difficulties associated with controlling selectivity. With this in mind, we focused on the development of new palladium (Pd)(0)-catalyzed C(sp(3))-H functionalization reactions for the synthesis of complex molecules, resulting in several new methods capable of solving these problems. We initially developed a concise synthetic method for the facile construction of oxindoles and spirooxindoles via a Pd-catalyzed benzylic C(sp(3))-H functionalization reaction. This method was subsequently extended to the synthesis of various heterocycles, including 2-arylindoles, benzocarbazole, indolocarbazole, indoloquinazolinone, and indoloquinazolinedione, as well as the total synthesis of several pyrrolophenanthridine alkaloids without the need for any protecting groups. This method was also successfully applied to the synthesis of the right-hand fragment of benzohopane from tetrahydro-2H-fluorene, which was constructed by a Pd-catalyzed benzylic C(sp(3))-H functionalization. In this review, we provide a detailed discussion of our most recent investigations pertaining to Pd(0)-catalyzed benzylic C(sp(3))-H functionalization.

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

    PubMed

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

    2005-11-09

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

  19. Stereoselective synthesis of stannyl enones via palladium-catalyzed and free radical hydrostannation of alkynyl ketones with trineophyltin hydride.

    PubMed

    Dodero, Verónica I; Koll, Liliana C; Faraoni, M Belén; Mitchell, Terence N; Podestá, Julio C

    2003-12-26

    A study on the addition of trineophyltin hydride (1) to alkynones under free radical (AIBN and Et3B) and palladium-catalyzed [(PPh3)2PdCl2] conditions is reported. The results obtained indicate that the addition of 1 to eight ynones catalyzed by bis(triphenylphosphine)palladium(II) chloride led in all cases to addition products in very high yields (80-96%). These additions take place with excellent regio- and stereochemistry, leading to the alpha adducts as major products in seven out of the eight cases studied. Also the E adducts, resulting from a syn attack, were the only (seven cases) or the predominant (one case) products. The radical hydrostannations initiated by AIBN of ynones 2-5 with 1 led to addition products in good yields (60-88%); with the more hindered ketones 6 and 7-9 the yields obtained were lower. The radical additions initiated by triethylboron to ynones 2-6 follow a similar pattern but with lower yields; no addition products in the hydrostannation of ynones 7-9 were detected. The new acyl-substituted vinylstannanes, owing to their greater stability compared with that of their tributyl- and trimethylstannyl analogues, can be purified by column chromatography using neutral alumina (in all cases) or silica gel 60 (in most cases) as adsorbents. Full 1H, 13C, and 119Sn NMR data are given.

  20. Efficient synthesis of π-conjugated molecules incorporating fluorinated phenylene units through palladium-catalyzed iterative C(sp(2))-H bond arylations.

    PubMed

    Abdelmalek, Fatiha; Derridj, Fazia; Djebbar, Safia; Soulé, Jean-François; Doucet, Henri

    2015-01-01

    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(sp(2))-H bonds.

  1. Cross-coupling of C(sp)-H Bonds with Organometallic Reagents via Pd(II)/Pd(0) Catalysis**

    PubMed

    Wasa, Masayuki; Engle, Keary M; Yu, Jin-Quan

    2010-12-01

    Palladium-catalyzed C-H activation/C-C bond-forming reactions have emerged as a promising class of synthetic tools in organic chemistry. Among the many different means of forging C-C bonds using Pd-mediated C-H activation, a new horizon in this field is Pd(II)-catalyzed cross-coupling of C-H bonds with organometallic reagents via a Pd(II)/Pd(0) catalytic cycle. While this type of reaction has proven to be effective for the selective functionalization of aryl C(sp(2))-H bonds, the focus of this review is on Pd(II)-catalyzed C(sp(3))-H activation/C-C cross-coupling, a topic of particular importance because reactions of this type enable fundamentally new methods for bond construction. Since our laboratory's initial report on cross-coupling of C-H bonds in 2006, this area has expanded rapidly, and the unique ability of Pd(II) catalysts to cleave and functionalize alkyl C(sp(3))-H bonds has been exploited to develop protocols for forming an array of C(sp(3))-C(sp(2)) and C(sp(3))-C(sp(3)) bonds. Furthermore, enantioselective C(sp(3))-H activation/C-C cross-coupling has been achieved through the use of chiral amino acid-derived ligands, offering a novel technique for producing enantioenriched molecules. Although this nascent field remains at an early stage of development, further investigations hold the potential to revolutionalize the way in which chiral molecules are synthesized in industrial and academic laboratories.

  2. Mechanistic Considerations in the Development and Use of Azine, Diazine and Azole N-Oxides in Palladium-Catalyzed Direct Arylation

    NASA Astrophysics Data System (ADS)

    Fagnou, Keith

    Azines, diazines or thiazole N-oxides are highly reactive substrates in palladium-catalyzed direct arylation reaction. For these reactions, the results are inconsistent with an SEAr reaction pathway and may best fit with a concerted metalation-deprotonation-like (CMD) mechanism.

  3. Palladium-catalyzed oxidative cyclization of aniline-tethered alkylidenecyclopropanes with O2: a facile protocol to selectively synthesize 2- and 3-vinylindoles.

    PubMed

    Cao, Bo; Simaan, Marwan; Marek, Ilan; Wei, Yin; Shi, Min

    2016-12-20

    A novel palladium-catalyzed oxidative cyclization of aniline-tethered alkylidenecyclopropanes using molecular oxygen as the terminal oxidant through β-carbon elimination of aminopalladation intermediates is disclosed. The reaction opens up an effective way to obtain a series of 2- and 3-vinylindoles which are important synthetic intermediates in many natural indole derivatives.

  4. Nucleophilic addition of benzimidazoles to alkynyl bromides/palladium-catalyzed intramolecular C-H vinylation: synthesis of benzo[4,5]imidazo[2,1-a]isoquinolines.

    PubMed

    Peng, Jinsong; Shang, Guoning; Chen, Chunxia; Miao, Zhongshuo; Li, Bin

    2013-02-01

    An efficient "one-pot" route for the synthesis of benzo[4,5]imidazo[2,1-a] isoquinolines has been developed via nucleophilic addition of 2-aryl benzimidazoles to alkynyl bromides and subsequent palladium-catalyzed intramolecular C-H vinylation.

  5. Palladium-Catalyzed One-Step Synthesis of Isoindole-1,3-diones by Carbonylative Cyclization of o-Halobenzoates and Primary Amines

    PubMed Central

    Worlikar, Shilpa A.; Larock, Richard C.

    2013-01-01

    The palladium-catalyzed aminocarbonylation of o-halobenzoates produces 2-substituted isoindole-1,3-diones in good yields. This methodology provides a good one-step approach to this important class of heterocycles and tolerates a variety of functional groups, including methoxy, alcohol, ketone, and nitro groups. PMID:18712929

  6. A Highly Substituted Lactone/Ester-Containing Furan Library by the Palladium-Catalyzed Carbonylation of Hydroxyl-Substituted 3-Iodofurans

    PubMed Central

    Cho, Chul-Hee; Larock, Richard C.

    2011-01-01

    Highly substituted lactone- and ester-containing furans have been prepared by the efficient palladium-catalyzed intramolecular cyclocarbonylation or intermolecular carboalkoxylation, respectively, of hydroxyl-containing 3-iodofurans, readily prepared by the iodocyclization of 2-(1-alkynyl)-2-alken-1-ones in the presence of various diols. PMID:21434604

  7. Palladium-catalyzed/norbornene-mediated ortho-amination/N-tosylhydrazone insertion reaction: an approach to the synthesis of ortho-aminated vinylarenes.

    PubMed

    Zhou, Ping-Xin; Ye, Yu-Ying; Ma, Jun-Wei; Zheng, Lan; Tang, Qian; Qiu, Yi-Feng; Song, Bo; Qiu, Zi-Hang; Xu, Peng-Fei; Liang, Yong-Min

    2014-07-18

    ortho-Aminated vinylarene derivatives were obtained via a reaction of aryl iodides, N-benzoyloxyamines, and N-tosylhydrazones. This approach involves a palladium-catalyzed, norbornene-mediated ortho-amination/N-tosylhydrazone insertion reaction. In this transformation, one C-N bond and one C-C bond are formed and an amine group is introduced at the ortho position successfully.

  8. Synthesis of 1H-indole-3-sulfonates via palladium-catalyzed tandem reactions of 2-alkynyl arylazides with sulfonic acids.

    PubMed

    Zhang, Xiaoxiang; Li, Ping; Lyu, Chang; Yong, Wanxiong; Li, Jing; Zhu, Xinbao; Rao, Weidong

    2017-07-26

    An efficient method for the synthesis of 1H-indole-3-sulfonates via palladium-catalyzed tandem reactions of 2-alkynyl arylazides with sulfonic acids has been developed. The desired products were obtained in good to excellent yields under mild reaction conditions. The reactions were shown to proceed very fast, in most cases, within 10 min.

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

    PubMed Central

    Abidi, Ahlem; Oueslati, Yosra

    2016-01-01

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

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

    PubMed

    Abidi, Ahlem; Oueslati, Yosra; Rezgui, Farhat

    2016-01-01

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

  11. Bench-Stable 5-Stannyl Triazoles by a Copper(I)-Catalyzed Interrupted Click Reaction: Bridge to Trifluoromethyltriazoles and Trifluoromethylthiotriazoles.

    PubMed

    Wei, Fang; Zhou, Tong; Ma, Yudao; Tung, Chen-Ho; Xu, Zhenghu

    2017-04-21

    Metalated triazoles are the key reactive intermediate of the current click reaction (CuAAC). Bench-stable 5-stannyl triazoles are obtained by a copper-catalyzed interrupted click reaction of easily available terminal alkynes. Subsequent palladium-catalyzed cross-coupling reactions, electrophilic trifluoromethylthiolation and trifluoromethylation, generate diverse 1,4,5-trisubstituted triazoles efficiently, which the traditional click reaction is unable to do.

  12. γ-Selective Cross-Coupling of Allylic Silanolate Salts with Aromatic Bromides Using Trialkylphosphonium Tetrafluoroborate Salts Prepared Directly from Phosphine•Borane Adducts

    PubMed Central

    Denmark, Scott E.; Werner, Nathan S.

    2011-01-01

    The γ-selective, palladium-catalyzed cross-coupling of sodium (Z)-2-butenyldiethylsilanolate with a variety of aromatic bromides is reported. The protocol provides high yields (73–94%) and site-selectivity (γ/α, 25:1–>99:1) in the coupling of electron-rich, electron-poor, sterically hindered, and heteroaromatic bromides. The use of a configurationally homogeneous (Z)-silanolate, nontransferable ethyl groups, and a sterically bulky trialkylphosphonium tetrafluoroborate salt (t-BuCy2PH+BF4−) prepared directly from the corresponding air-stable phosphine•borane adduct are critical to the success of the method. PMID:21830766

  13. 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.

  14. Enantioselective Palladium-Catalyzed Carbene Insertion into the N-H Bonds of Aromatic Heterocycles.

    PubMed

    Arredondo, Vanessa; Hiew, Stanley C; Gutman, Eugene S; Premachandra, Ilandari Dewage Udara Anulal; Van Vranken, David L

    2017-03-15

    C3-substituted indoles and carbazoles react with α-aryl-α-diazoesters under palladium catalysis to form α-(N-indolyl)-α-arylesters and α-(N-carbazolyl)-α-arylesters. The products result from insertion of a palladium-carbene ligand into the N-H bond of the aromatic N-heterocycles. Enantioselection was achieved using a chiral bis(oxazoline) ligand, in many cases with high enantioselectivity (up to 99 % ee). The method was applied to synthesize the core of a bioactive carbazole derivative in a concise manner.

  15. 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.

  16. Hydrogen-bond-assisted activation of allylic alcohols for palladium-catalyzed coupling reactions.

    PubMed

    Gumrukcu, Yasemin; de Bruin, Bas; Reek, Joost N H

    2014-03-01

    We report direct activation of allylic alcohols using a hydrogen-bond-assisted palladium catalyst and use this for alkylation and amination reactions. The novel catalyst comprises a palladium complex based on a functionalized monodentate phosphoramidite ligand in combination with urea additives and affords linear alkylated and aminated allylic products selectively. Detailed kinetic analysis show that oxidative addition of the allyl alcohol is the rate-determining step, which is facilitated by hydrogen bonds between the alcohol, the ligand functional group, and the additional urea additive.

  17. Construction of Nine-Membered Heterocycles through Palladium-Catalyzed Formal [5+4] Cycloaddition.

    PubMed

    Yang, Li-Cheng; Rong, Zi-Qiang; Wang, Ya-Nong; Tan, Zher Yin; Wang, Min; Zhao, Yu

    2017-03-06

    The first catalytic formal [5+4] cycloaddition to prepare nine-membered heterocycles is presented. Under palladium catalysis, the reaction of N-tosyl azadienes and substituted vinylethylene carbonates (VECs) proceeds smoothly to produce benzofuran-fused heterocycles in uniformly high efficiency. Highly diastereoselective functionalization of the nine-membered heterocycles through peripheral attack is also demonstrated.

  18. Palladium-catalyzed carbonylative synthesis of quinazolinones from 2-aminobenzamide and aryl bromides.

    PubMed

    Wu, Xiao-Feng; He, Lin; Neumann, Helfried; Beller, Matthias

    2013-09-16

    C from CO! A straightforward procedure for the carbonylative synthesis of quinazolinones from readily available 2-aminobenzamide and aryl bromides has been developed. In the presence of a palladium catalyst, various quinazolinones were produced in moderate to excellent yields. Remarkably, no chromatography was needed for purification (see scheme).

  19. Regiospecific and stereospecific palladium-catalyzed cycloaddition of azetidines and carbodiimides

    SciTech Connect

    Baeg, Jin-Ook; Bensimon, C.; Alper, H.

    1995-01-13

    Acetidines react with carbodiimides in the presence of bis(benzonitrile)palladium dischloride to form tetrahydrophyrimidin-2-imines in 64-97% yields. The reaction is both regio- and stereospecific, the cycloaddition occurring with retention of configuration of the carbon centers bearing the substitutent groups. 2 figs.

  20. 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.

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

    PubMed

    Hajra, Alakananda; Wei, Ye; Yoshikai, Naohiko

    2012-11-02

    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.

  2. 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

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

    PubMed

    Alacid, Emilio; Nájera, Carmen

    2009-11-06

    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.

  4. Palladium(II)-Catalyzed Annulation of Alkynes with 2-(Cyanomethyl)phenylboronates Leading to 3,4-Disubstituted 2-Naphthalenamines.

    PubMed

    Tsukamoto, Hirokazu; Ikeda, Taishi; Doi, Takayuki

    2016-03-04

    1,2-Bis(diphenylphosphino)ethane (dppe)-ligated palladium(II) complexes catalyze the annulation of internal alkynes with 2-(cyanomethyl)phenylboronates to provide 3,4-disubstituted-2-naphthalenamines in good yields. The annulation reaction proceeds under mild and neutral conditions and requires methanol as an essential solvent. In addition to symmetrical alkynes, unsymmetrical alkynes substituted by aryl, alkyl, and alkynyl groups participate in the annulation to afford the corresponding 2-naphthalenamines with electron-withdrawing sp(2)- and sp-carbons preferentially located at the C-3 position. Substituents including an alkyl or alkoxy group on the cyanomethyl moiety and a halogen atom on the benzene ring in the boronates are compatible with the reaction conditions. The annulation proceeds through the transmetalation of the palladium(II) complexes with the boronates and alkyne insertion followed by nucleophilic addition of the generated alkenylpalladium(II) species to the intramolecular cyano group. Stoichiometric reactions revealed that the methanol solvent was effective for both transmetalation and catalyst regeneration.

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

    PubMed Central

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

    2012-01-01

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

  6. 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

    2015-03-07

    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.

  7. Direct palladium-catalyzed C-3 arylation of free (NH)-indoles with aryl bromides under ligandless conditions.

    PubMed

    Bellina, Fabio; Benelli, Francesca; Rossi, Renzo

    2008-07-18

    A new method for the efficient, practical, and highly regioselective direct palladium-catalyzed C-3 arylation of free (NH)-indole and its electron-rich 1-unsubstituted derivatives under ligandless conditions is described. The reactions, which are run outside a glovebox without purification of solvent and reagents, involve treatment of free (NH)-indoles with activated, unactivated, and deactivated aryl bromides in refluxing toluene in the presence of K2CO3 as the base and a catalyst system consisting of a combination of Pd(OAc)2 and benzyl(tributyl)ammonium chloride. The experimental results are consistent with a catalytic cycle based on an electrophilic palladation pathway at the 3-position of 1-indolyl potassium salts.

  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. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Synthesis of indoles by intermolecular cyclization of unfunctionalized nitroarenes and alkynes, catalyzed by palladium-phenanthroline complexes.

    PubMed

    Ragaini, Fabio; Rapetti, Andrea; Visentin, Elena; Monzani, Michela; Caselli, Alessandro; Cenini, Sergio

    2006-05-12

    Palladium-phenanthroline complexes efficiently catalyze the reaction of nitroarenes with arylalkynes and CO to give 3-arylindoles by an ortho-C-H functionalization of the nitroarene ring. Both electron-withdrawing and electron-donating substituents are tolerated on the nitroarene, except for bromide and activated chloride. Nitroarenes bearing electron-withdrawing substituents react faster, but the selectivity of the reaction depends on both polar and radical stabilization effects. Among those tested, only arylalkynes afforded indoles under the investigated conditions. The reaction mechanism was partly investigated. The kinetics is first order in nitroarene concentration and the rate-determining step of the cycle is the initial nitroarene reduction. No primary isotope effect is observed on either rate or selectivity, implying that the cyclization step is fast.

  10. 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

  11. Enantioselective synthesis of α-quaternary Mannich adducts by palladium-catalyzed allylic alkylation: total synthesis of (+)-sibirinine.

    PubMed

    Numajiri, Yoshitaka; Pritchett, Beau P; Chiyoda, Koji; Stoltz, Brian M

    2015-01-28

    A catalytic enantioselective method for the synthesis of α-quaternary Mannich-type products is reported. The two-step sequence of (1) Mannich reaction followed by (2) decarboxylative enantioselective allylic alkylation serves as a novel strategy to in effect access asymmetric Mannich-type products of "thermodynamic" enolates of substrates possessing additional enolizable positions and acidic protons. Palladium-catalyzed decarboxylative allylic alkylation enables the enantioselective synthesis of five-, six-, and seven-membered ketone, lactam, and other heterocyclic systems. The mild reaction conditions are notable given the acidic free N-H groups and high functional group tolerance in each of the substrates. The utility of this method is highlighted in the first total synthesis of (+)-sibirinine.

  12. 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.

  13. Dehydrative cross-coupling reactions of allylic alcohols with olefins.

    PubMed

    Gumrukcu, Yasemin; de Bruin, Bas; Reek, Joost N H

    2014-08-25

    The direct dehydrative activation of allylic alcohols and subsequent cross-coupling with alkenes by using palladium catalyst containing a phosphoramidite ligand is described. The activation of the allyl alcohol does not require stoichiometric additives, thus allowing clean, waste-free reactions. The scope is demonstrated by application of the protocol to a series allylic alcohols and vinyl arenes, leading to variety of 1,4-diene products. Based on kinetic studies, a mechanism is proposed that involves a palladium hydride species that activates the allyl alcohol to form the allyl intermediate.

  14. Experimental and theoretical study on palladium-catalyzed C-P bond formation via direct coupling of triarylbismuths with P(O)-H compounds.

    PubMed

    Wang, Tao; Sang, Shuai; Liu, Liu; Qiao, Hongwei; Gao, Yuxing; Zhao, Yufen

    2014-01-17

    A novel and highly efficient Pd-catalyzed cross-coupling of triarylbismuths with a variety of P(O)-H compounds has been developed that proceeds smoothly without exclusion of moisture or air and provides a general and powerful tool for the preparation of various valuable arylphosphonates, arylphosphinates, and arylphosphine oxides, with high atom-economy, operational simplicity of the procedure, and good to high yield. The coupling reaction is the first example of transition-metal-catalyzed C-P bond construction using triarylbismuth compounds as substrates. DFT calculations reveal that C-P bond formation is the rate-determing step.

  15. Palladium Catalyzed Regiocontrolled α-Arylation of Trimethylsilyl Enol Ethers with Aryl Halides

    PubMed Central

    Iwama, Tetsuo

    2008-01-01

    Inter- and intramolecular arylations of trimethylsilyl enol ethers with aryl halides are accomplished regiospecifically in the presence of a palladium catalyst and tributyltin fluoride in refluxing benzene or toluene. The optimal catalyst system called for the use of Pd2(dba)3 and tri-tert-butylphosphine in ca. 1:2 ratio. Aryl iodides, bromides and chlorides are all effective arylation partners in this reaction. PMID:17134257

  16. P-chiral phosphine-sulfonate/palladium-catalyzed asymmetric copolymerization of vinyl acetate with carbon monoxide.

    PubMed

    Nakamura, Akifumi; Kageyama, Takeharu; Goto, Hiroki; Carrow, Brad P; Ito, Shingo; Nozaki, Kyoko

    2012-08-01

    Utilization of palladium catalysts bearing a P-chiral phosphine-sulfonate ligand enabled asymmetric copolymerization of vinyl acetate with carbon monoxide. The obtained γ-polyketones have head-to-tail and isotactic polymer structures. The origin of the regio- and stereoregularities was elucidated by stoichiometric reactions of acylpalladium complexes with vinyl acetate. The present report for the first time demonstrates successful asymmetric coordination-insertion (co)polymerization of vinyl acetate.

  17. A general palladium-catalyzed carbonylative synthesis of chromenones from salicylic aldehydes and benzyl chlorides.

    PubMed

    Wu, Xiao-Feng; Wu, Lipeng; Jackstell, Ralf; Neumann, Helfried; Beller, Matthias

    2013-09-09

    Cute CO! An interesting and straightforward procedure for the carbonylative synthesis of chromenones from readily available salicylic aldehydes and benzyl chlorides has been developed (see scheme; DPPP = 1,3-bis(diphenylphosphino)propane). In the presence of a palladium catalyst, various coumarins were produced in good to excellent yields. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Regioselective hydrothiolation of alkenes bearing heteroatoms with thiols catalyzed by palladium diacetate.

    PubMed

    Tamai, Taichi; Ogawa, Akiya

    2014-06-06

    In sharp contrast to many examples of transition-metal-catalyzed hydrothiolation of alkynes, the corresponding catalytic addition of thiols to alkenes has remained undeveloped. However, a novel Pd-catalyzed addition of thiols to alkenes bearing a heteroatom, such as oxygen and nitrogen, is found to proceed under mild conditions to give the corresponding Markovnikov adducts, regioselectively, in good yields.

  19. Role of Lewis acid additives in a palladium catalyzed directed C-H functionalization reaction of benzohydroxamic acid to isoxazolone.

    PubMed

    Athira, C; Sunoj, Raghavan B

    2016-12-20

    Metallic salts as well as protic additives are widely employed in transition metal catalyzed C-H bond functionalization reactions to improve the efficiency of catalytic protocols. In one such example, ZnCl2 and pivalic acid are used as additives in a palladium catalyzed synthesis of isoxazolone from a readily available benzohydroxamic acid under one pot conditions. In this article, we present some important mechanistic insights into the role of ZnCl2 and pivalic acid, gained by using density functional theory (M06) computations. Two interesting modes of action of ZnCl2 are identified in various catalytic steps involved in the formation of isoxazolone. The conventional Lewis acid coordination wherein zinc chloride (ZnCl2·(DMA)) binds to the carbonyl group is found to be more favored in the C-H activation step. However, the participation of a hetero-bimetallic Pd-Zn species is preferred in reductive elimination leading to Caryl-N bond formation. Pivalic acid helps in relay proton transfer in C-H bond activation through a cyclometallation deprotonation (CMD) process. The explicit inclusion of ZnCl2 and solvent N,N-dimethyl acetamide (DMA) stabilizes the transition state and also helps reduce the activation barrier for the C-H bond activation step. The electronic communication between the two metal species is playing a crucial role in stabilizing the Caryl-N bond formation transition state through a Pd-Zn hetero-bimetallic interaction.

  20. A Genetically Encoded Alkyne Directs Palladium-Mediated Protein Labeling on Live Mammalian Cell Surface

    PubMed Central

    2015-01-01

    The merging of site-specific incorporation of small bioorthogonal functional groups into proteins via amber codon suppression with bioorthogonal chemistry has created exciting opportunities to extend the power of organic reactions to living systems. Here we show that a new alkyne amino acid can be site-selectively incorporated into mammalian proteins via a known orthogonal pyrrolysyl-tRNA synthetase/tRNACUA pair and directs an unprecedented, palladium-mediated cross-coupling reaction-driven protein labeling on live mammalian cell surface. A comparison study with the alkyne-encoded proteins in vitro indicated that this terminal alkyne is better suited for the palladium-mediated cross-coupling reaction than the copper-catalyzed click chemistry. PMID:25347611

  1. Palladium-catalyzed α-arylation of carbonyls in the de novo synthesis of aromatic heterocycles

    PubMed Central

    Potukuchi, Harish K.; Spork, Anatol P.

    2015-01-01

    Aromatic heterocycles are a very well represented motif in natural products and have found various applications in chemistry and material science, as well as being commonly found in pharmaceutical agents. Thus, new and efficient routes towards this class of compound are always desirable, particularly if they expand the scope of chemical methodology or facilitate more effective pathways to complex substitution patterns. This perspective covers recent developments in the de novo synthesis of aromatic heterocycles via palladium-catalysed α-arylation reactions of carbonyls, which is itself a powerful transformation that has undergone significant development in recent years. PMID:25789887

  2. Mechanistic aspects of the alternating copolymerization of carbon monoxide with olefins catalyzed by cationic palladium complexes

    SciTech Connect

    Batistini, A.; Consiglio, G.

    1992-05-01

    The copolymerization of propylene with carbon monoxide using a catalytic system based on palladium acetate, modified with the atropisomeric chiral ligand (S)-(6,6{prime}-dimethylbiphenyl-2,2{prime}-diyl)bis(dicyclohexylphosphine), gives poly[spiro-2,5-(3-methyltetrahydrofuran)]. This material is transformed into the isomeric poly(1-oxo-2-methyltrimethylene) by dissolution in hexafluoro-2-propanol and precipitation with methanol. A mechanism based on a carbene intermediate is proposed in order to account for the formation of the polyketone material in the spiroketal form. 22 refs., 1 fig.

  3. Aerobic, Palladium-Catalyzed Dioxygenation of Alkenes Enabled by Catalytic Nitrite**

    PubMed Central

    Wickens, Zachary K.; Guzmán, Pablo E.; Grubbs, Robert H.

    2014-01-01

    Catalytic nitrite was found to enable carbon-oxygen bond-forming reductive elimination from unstable alkyl palladium intermediates, providing dioxygenated products from alkenes. A variety of functional groups are tolerated and high yields (up to 94%) are observed with many substrates, including a multi-gram scale reaction. Nitrogen dioxide, which could form from nitrite under the reaction conditions, was shown to be kinetically competent in the dioxygenation of alkenes. Furthermore, the reductive elimination event was probed with 18 O-labeling experiments, which demonstrated that both oxygen atoms in the difunctionalized products are derived from one molecule of acetic acid. PMID:25376666

  4. Proximity effects in the palladium-catalyzed substitution of aryl fluorides.

    PubMed

    Bahmanyar, S; Borer, Bennett C; Kim, Young Mi; Kurtz, David M; Yu, Shu

    2005-03-17

    [reaction: see text] The aryl fluoride bond has long been considered inert toward Pd-catalyzed insertion reactions. This paper reports for the first time that aryl fluorides bearing an o-carboxylate group can undergo Pd-catalyzed couplings. On the basis of this computational study and subsequent experimental verifications of its predictions, we herein report that such reactions are facilitated by stabilization of the transition state by proximal oxyanions.

  5. One-pot synthesis of 2-amino-4(3H)-quinazolinones via ring-opening of isatoic anhydride and palladium-catalyzed oxidative isocyanide-insertion.

    PubMed

    Ji, Fei; Lv, Mei-Fang; Yi, Wen-Bin; Cai, Chun

    2014-08-14

    An efficient and practical two-step process has been developed for the synthesis of 2-amino-4(3H)-quinazolinones via ring-opening of isatoic anhydride and palladium-catalyzed oxidative isocyanide-insertion in one pot. This regioselective procedure could construct a wide range of 2-amino-4(3H)-quinazolinones in moderate to excellent yields. Furthermore, the methodology also had distinct advantages of easily accessible starting materials and operational simplicity.

  6. Experimental and Mechanistic Analysis of the Palladium-Catalyzed Oxidative C8-Selective C–H Homocoupling of Quinoline N-Oxides

    PubMed Central

    Stephens, David E.; Lakey-Beitia, Johant; Chavez, Gabriel; Ilie, Carla; Arman, Hadi D.

    2016-01-01

    A novel site-selective palladium-catalyzed oxidative C8–H homocoupling reaction of quinoline N-oxides has been developed. The reaction affords substituted 8,8'-biquinolyl N,N'-dioxides that can be readily converted to a variety of functionalized 8,8'-biquinolyls. Mechanistic studies point to the crucial role of the oxidant and a non-innocent behavior of acetic acid as a solvent. PMID:25966913

  7. Synthesis of D-abrines by palladium-catalyzed reaction of ortho-iodoanilines with N-Boc-N-methylalanyl-substituted acetaldehyde and acetylene.

    PubMed

    Danner, Paulami; Morkunas, Marius; Maier, Martin E

    2013-05-17

    A novel strategy to N-Boc-N-methyl--tryptophans (abrine derivatives) was developed that relies on the palladium-catalyzed annulation of ortho-iodoanilines 12 with either N-Boc-N-methyl-propargylglycine 16 or aldehyde 11. Both 11 and 16 can be prepared from d-serine. An alternative route to propargylglycine 16 utilizes an enantioselective propargylation reaction of glycine imine 17.

  8. Palladium(II)-Catalyzed C-H Bond Activation/C-C and C-O Bond Formation Reaction Cascade: Direct Synthesis of Coumestans.

    PubMed

    Neog, Kashmiri; Borah, Ashwini; Gogoi, Pranjal

    2016-12-02

    A palladium catalyzed cascade reaction of 4-hydroxycoumarins and in situ generated arynes has been developed for the direct synthesis of coumestans. This cascade strategy proceeds via C-H bond activation/C-O and C-C bond formations in a single reaction vessel. This methodology affords moderate to good yields of coumestans and is tolerant of a variety of functional groups including halide. The methodology was applied to the synthesis of natural product flemichapparin C.

  9. Palladium-catalyzed synthesis of 2-alkenyl-3-arylindoles via a dual α-arylation strategy: formal synthesis of the antilipemic drug fluvastatin.

    PubMed

    Kale, Ajit Prabhakar; Kumar, Gangam Srikanth; Kapur, Manmohan

    2015-12-07

    A new approach has been developed for the synthesis of substituted 2-alkenyl-3-arylindoles. The strategy comprises palladium-catalyzed dual α-arylation of TES-enol ethers of enones as the key step. This methodology results in products with very good yields and the regioselectivity is exclusive. We have also successfully used this dual α-arylation methodology in the formal synthesis of the cholesterol-lowering drug fluvastatin.

  10. Palladium(II)-Catalyzed, Heteroatom-Directed, Regioselective C-H Nitration of Anilines Using Pyrimidine as a Removable Directing Group.

    PubMed

    Pawar, Govind Goroba; Brahmanandan, Abhilashamole; Kapur, Manmohan

    2016-02-05

    A new palladium-catalyzed, heteroatom-directed strategy for C-H nitration of anilines is described. This C-H functionalization reaction is highly ortho-selective and results in very good yields. The highlight of the work is the use of pyrimidine as the removable directing group. This approach constitutes one of the rare methods of ortho-nitration of anilines, a reaction that is normally very difficult to achieve via traditional approaches.

  11. Palladium-catalyzed sequential one-pot reaction of aryl bromides with O-homoallylhydroxylamines: synthesis of N-aryl-beta-amino alcohols.

    PubMed

    Peng, Jinsong; Jiang, Dahong; Lin, Wenqing; Chen, Yuanwei

    2007-05-07

    The palladium-catalyzed sequential one-pot N-arylation-carbo-amination-C-arylation of O-homoallylhydroxylamines with two different aryl bromides provides rapid entry to differentially arylated N-aryl-3-arylmethylisoxazolidines in good yields with excellent diastereoselectivity. The obtained isoxazolidines can be reductively cleaved to cis-N-aryl-beta-amino alcohols in short times and in high yields at room temperature.

  12. Synthesis of Benzo[c]silole Derivatives Bearing a Tetrasubstituted Exocyclic C=C Double Bond by Palladium-Catalyzed Domino Reactions.

    PubMed

    Wagner, Patrick; Gulea, Mihaela; Suffert, Jean; Donnard, Morgan

    2017-06-01

    The synthesis of diversely substituted 2,3-dihydro-benzo[c]siloles through an unprecedented palladium-catalyzed domino sequence is reported, involving a cyclocarbopalladation of an internal silylalkyne. This reaction proceeds with complete stereoselectivity to lead to a fully substituted exocyclic C=C double bond. Notably, the overall domino sequence appears to be crucial to obtain the desired cyclic vinylsilanes. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Palladium-catalyzed synthesis of uridines on polystyrene-based solid supports.

    PubMed

    Aucagne, Vincent; Berteina-Raboin, Sabine; Guenot, Pierre; Agrofoglio, Luigi A

    2004-01-01

    In this paper, the solid-phase synthesis of various substituted pyrimidine nucleosides is described starting from 2'-deoxyuridine, which has been attached through a base labile linker to polystyrene resins. The utility of the Pd(0) cross-coupling to functionalized pyrimidine nucleosides is expanded herein to include reactions of resin-supported 5-iodo-2'-deoxyuridine under Sonogashira, Stille, Heck, and Suzuki conditions. Upon cleavage with MeONa, a library of 5-substituted pyrimidine nucleosides was obtained in good (under Sonogashira and Stille conditions) to moderate (under Heck or Suzuki conditions) yields and high purity. Except the Suzuki-type reactions, the presented methods exhibit a significant improvement and facilitate the synthetic procedure with respect to purification and yields (determined after filtration over silica gel).

  14. Selenide-Catalyzed Stereoselective Construction of Tetrasubstituted Trifluoromethylthiolated Alkenes with Alkynes.

    PubMed

    Wu, Jin-Ji; Xu, Jia; Zhao, Xiaodan

    2016-10-17

    The efficient regio- and stereoselective construction of tetrasubstituted alkenes is challenging and very important. For this purpose, we have developed an efficient approach to synthesize tetrasubstituted trifluoromethylthiolated alkenes from simple alkynes in excellent regio- and stereoselectivities by selenide-catalyzed multicomponent coupling. Using this method, trifluoromethylthiolated alkenyl triflates and arenes were achieved. In particular, the triflates could be further converted into carbofunctionalized alkenes by palladium-catalyzed cross-coupling reactions. Our method provides a new pathway for the construction of trifluoromethylthiolated tricarboalkenes. This work presents the first example of selenide-catalyzed trifluoromethylthiolation of alkynes and enables the challenging functionalizations of alkynes.

  15. Silver-catalyzed late-stage fluorination.

    PubMed

    Tang, Pingping; Furuya, Takeru; Ritter, Tobias

    2010-09-01

    Carbon-fluorine bond formation by transition metal catalysis is difficult, and only a few methods for the synthesis of aryl fluorides have been developed. All reported transition-metal-catalyzed fluorination reactions for the synthesis of functionalized arenes are based on palladium. Here we present silver catalysis for carbon-fluorine bond formation. Our report is the first example of the use of the transition metal silver to form carbon-heteroatom bonds by cross-coupling catalysis. The functional group tolerance and substrate scope presented here have not been demonstrated for any other fluorination reaction to date.

  16. An improved palladium-catalyzed conversion of aryl and vinyl triflates to bromides and chlorides.

    PubMed

    Pan, Jun; Wang, Xinyan; Zhang, Yong; Buchwald, Stephen L

    2011-09-16

    A facile Pd-catalyzed conversion of aryl and vinyl triflates to aryl and vinyl halides (bromides and chlorides) is described. This method allows convenient access to a variety of aryl, heteroaryl, and vinyl halides in good to excellent yields and with greatly simplified conditions relative to our previous report. © 2011 American Chemical Society

  17. An Improved Palladium-Catalyzed Conversion of Aryl and Vinyl Triflates to Bromides and Chlorides

    PubMed Central

    Pan, Jun; Wang, Xinyan; Zhang, Yong; Buchwald, Stephen L.

    2011-01-01

    A facile Pd-catalyzed conversion of aryl and vinyl triflates to aryl and vinyl halides (bromides and chlorides) is described. This method allows convenient access to a variety of aryl, heteroaryl, and vinyl halides in good to excellent yields and with greatly simplified conditions relative to our previous report. PMID:21863838

  18. A Palladium-Catalyzed Asymmetric Allylic Alkylation Approach to α-Quaternary γ-Butyrolactones.

    PubMed

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

    2017-01-06

    The Pd-catalyzed asymmetric allylic alkylation (Pd-AAA) of enol carbonates derived from γ-butyrolactones is reported, affording the corresponding enantioenriched α,α'-disubstituted γ-butyrolactones in both high yields and high enantioselectivities (up to 94% ee). This method was eventually applied to the synthesis of chiral spirocyclic compounds.

  19. Enantioselective synthesis of planar chiral ferrocenes via palladium-catalyzed direct coupling with arylboronic acids.

    PubMed

    Gao, De-Wei; Shi, Yan-Chao; Gu, Qing; Zhao, Zheng-Le; You, Shu-Li

    2013-01-09

    Enantioselective Pd(II)-catalyzed direct coupling of aminomethylferrocene derivatives with boronic acids was realized. With commercially available Boc-L-Val-OH as a ligand, planar-chiral ferrocenes could be synthesized in yields of 14-81% with up to 99% ee under mild conditions.

  20. Enantioselective synthesis of planar chiral ferrocenes via palladium-catalyzed annulation with diarylethynes.

    PubMed

    Shi, Yan-Chao; Yang, Rong-Fei; Gao, De-Wei; You, Shu-Li

    2013-01-01

    When Boc-L-Val-OH was used as a ligand for the enantioselective Pd(II)-catalyzed annulation of N,N-substituted aminomethyl ferrocene derivatives with diarylethynes, ferrocenes with planar chirality could be achieved with excellent enantioselectivity (up to 99% ee).

  1. Enantioselective synthesis of planar chiral ferrocenes via palladium-catalyzed annulation with diarylethynes

    PubMed Central

    Shi, Yan-Chao; Yang, Rong-Fei; Gao, De-Wei

    2013-01-01

    Summary When Boc-L-Val-OH was used as a ligand for the enantioselective Pd(II)-catalyzed annulation of N,N-substituted aminomethyl ferrocene derivatives with diarylethynes, ferrocenes with planar chirality could be achieved with excellent enantioselectivity (up to 99% ee). PMID:24062858

  2. Synthesis and evaluation of the substrate activity of C-6 substituted purine ribosides with E. coli purine nucleoside phosphorylase: palladium mediated cross-coupling of organozinc halides with 6-chloropurine nucleosides.

    PubMed

    Hassan, Abdalla E A; Abou-Elkhair, Reham A I; Riordan, James M; Allan, Paula W; Parker, William B; Khare, Rashmi; Waud, William R; Montgomery, John A; Secrist, John A

    2012-01-01

    A series of C-6 alkyl, cycloalkyl, and aryl-9-(β-d-ribofuranosyl)purines were synthesized and their substrate activities with Escherichia coli purine nucleoside phosphorylase (E. coli PNP) were evaluated. (Ph(3)P)(4)Pd-mediated cross-coupling reactions of 6-chloro-9-(2,3,5-tri-O-acetyl-β-d-ribofuranosyl)-purine (6) with primary alkyl (Me, Et, n-Pr, n-Bu, isoBu) zinc halides followed by treatment with NH(3)/MeOH gave the corresponding 6-alkyl-9-(β-d-ribofuranosyl)purine derivatives 7-11, respectively, in good yields. Reactions of 6 with cycloalkyl(propyl, butyl, pentyl)zinc halides and aryl (phenyl, 2-thienyl)zinc halides gave under similar conditions the corresponding 6-cyclopropyl, cyclobutyl, cyclopentyl, phenyl, and thienyl -9-(β-d-ribofuranosyl)purine derivatives 12-16, respectively in high yields. E. coli PNP showed a high tolerance to the steric and hydrophobic environment at the 6-position of the synthesized purine ribonucleosides. Significant cytotoxic activity was observed for 8, 12, 15, and 16. Evaluation of 12 and 16 against human tumor xenografts in mice did not demonstrate any selective antitumor activity. In addition, 6-methyl-9-(β-d-arabinofuranosyl)purine (18) was prepared and evaluated. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  3. 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.

  4. 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.

  5. 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.

  6. One-Pot Three-Step Synthesis of 1,2,3-Triazoles by Copper-Catalyzed Cycloaddition of Azides with Alkynes formed by a Sonogashira Cross-Coupling and Desilylation

    PubMed Central

    Friscourt, Frédéric; Boons, Geert-Jan

    2010-01-01

    A microwave-assisted one-pot, three-step Sonogashira cross coupling-desilylation-cycloaddition sequence was developed for the convenient preparation of 1,4-disubstituted 1,2,3-triazoles starting from a range of halides, acyl chlorides, ethynyltrimethylsilane and azides. PMID:20942390

  7. A remarkable regiocontrol in the palladium-catalyzed silylstannylation of fluoroalkylated alkynes--highly regio- and stereoselective synthesis of multi-substituted fluorine-containing alkenes.

    PubMed

    Konno, Tsutomu; Kinugawa, Ryoko; Ishihara, Takashi; Yamada, Shigeyuki

    2014-03-14

    On treating fluorine-containing internal alkynes with 1.2 equiv. of (trimethylsilyl)tributyltin in the presence of 2.5 mol% of Pd(PPh3)2Cl2 in THF at the reflux temperature for 6 h, the silylstannylation reaction proceeded smoothly to afford the corresponding silylstannylated adducts in high yields in a highly regio- and cis-selective manner. Switching the palladium catalyst from Pd(PPh3)2Cl2 to Pd(t-BuNC)2Cl2 promoted the formation of silylstannylated adducts with opposite regioselectivity. The thus obtained silylstannylated adducts were subjected to Stille cross-coupling reactions to furnish the corresponding fluoroalkylated vinylsilanes whose C-Si bond was converted to a C-C bond by treating with aldehyde in the presence of TBAF and Zn(OTf)2, the corresponding fluoroalkylated tetra-substituted alkenes being afforded in moderate to good yields with a defined stereochemistry.

  8. Silver-mediated palladium-catalyzed direct C-H arylation of 3-bromoisothiazole-4-carbonitrile.

    PubMed

    Ioannidou, Heraklidia A; Koutentis, Panayiotis A

    2011-03-18

    Silver(I) fluoride-mediated Pd-catalyzed C-H direct arylation/heteroarylation of 3-bromoisothiazole-4-carbonitrile (1a) gives twenty-four 5-aryl/heteroaryl-3-bromoisothiazole-4-carbonitriles. The reaction was partially optimized with respect to catalyst, ligand, and base. During this study 3,3'-dibromo-5,5'-biisothiazole-4,4'-dicarbonitrile (3a) was isolated as a byproduct and subsequently prepared via the silver-mediated Pd-catalyzed oxidative dimerization of 3-bromoisothiazole-4-carbonitrile in 67% yield. The analogous phenylation and oxidative dimerization of 3-chloroisothiazole-4-carbonitrile (1b) gave 3-chloro-5-phenylisothiazole-4-carbonitrile (4) and 3,3'-dichloro-5,5'-biisothiazole-4,4'-dicarbonitrile (3b) in 96% and 69% yields, respectively.

  9. Facile synthesis of fluoroalkenes by palladium-catalyzed reductive defluorination of allylic gem-difluorides.

    PubMed

    Narumi, Tetsuo; Tomita, Kenji; Inokuchi, Eriko; Kobayashi, Kazuya; Oishi, Shinya; Ohno, Hiroaki; Fujii, Nobutaka

    2007-08-16

    Chemo- and stereoselective synthesis of fluoroalkenes was achieved in excellent yields via Pd-catalyzed C-F bond activation. In this transformation, Et3N plays a crucial role to produce reactive hydride species such as Ph(EtO)SiH2 and Ph(EtO)2SiH by promoting dehydrogenative coupling. The reaction proceeds efficiently at 50 degrees C with a variety of substrates and is also useful for the synthesis of fluoroalkene peptidomimetics.

  10. Indole synthesis by palladium-catalyzed tandem allylic isomerization - furan Diels-Alder reaction.

    PubMed

    Xu, Jie; Wipf, Peter

    2017-08-30

    A Pd(0)-catalyzed elimination of an allylic acetate generates a π-allyl complex that is postulated to initiate a novel intramolecular Diels-Alder cycloaddition to a tethered furan (IMDAF). Under the reaction conditions, this convergent, microwave-accelerated cascade process provides substituted indoles in moderate to good yields after Pd-hydride elimination, aromatization by dehydration, and in situ N-Boc cleavage.

  11. Palladium-catalyzed oxidative diffusion for tritium extraction from breeder-blanket fluids at low concentrations

    NASA Astrophysics Data System (ADS)

    Hsu, Cheazone; Buxbaum, Robert E.

    1986-11-01

    Oxidative diffusion can extract hydrogen from metal solutions at extremely low partial pressures. The hydrogen diffuses through a metal membrane and is oxidized to water. The oxidation reaction produces the very low downstream pressures that drive the flux. This method is attractive because the flux can be proportional to the square-root of upstream pressure. For fusion reactors with liquid lithium or lithium-lead alloy breeder blankets, permeation windows provide a simple, cheap tritium extraction method. Interdiffusion rates, separation flux, window size, helium contents, tritium holdup costs, and overall costs are calculated for membranes of palladium-coated zirconium, niobium, vanadium, nickel and stainless-steel. For extracting tritium from liquid lithium using the cheapest windows, Zr-Pd, the material and labor cost is 8.0 M at 1 wppm, and is inversely proportional to tritium concentration in the lithium. The tritium holdup cost for the windows is 4.8 M, and for the blanket it is proportional to the blanket volume and concentration. An overall economic optimization suggests that 1 to 1.5 wppm in lithium is optimal. For extracting tritium from 17Li83Pb at 0.26 wppb, the cheapest window is V-Pd; the cost is 2.6 M$, and the tritium holdup is negligible.

  12. Palladium-indium catalyzed reduction of N-nitrosodimethylamine: indium as a promoter metal.

    PubMed

    Davie, Matthew G; Shih, Kaimin; Pacheco, Federico A; Leckie, James O; Reinhard, Martin

    2008-04-15

    An emerging technology for the removal of N-nitrosodimethylamine (NDMA) from drinking and groundwater is reductive destruction using noble metal catalysts and hydrogen gas as a reducing agent. Bimetallic palladium-indium (Pd-In) supported on alumina combines the ability of Into activate NDMA with the hydrogen activating properties of Pd. This study examined the effect of In addition to a commercial 5% Pd by weight on gamma-Al2O3 catalyst on the efficacy of NDMA reduction. The pseudo-first-order rate constant increased proportionately to In loading from 0.057 h(-1) for 0% In to a maximum of 0.25 h(-1) for 1% In and then decreased with additional in loading. Data suggest that hydrogen activation occurred only on Pd surfaces and In activated NDMA 20 times more effectively than Pd on a mass basis. The rate-limiting factor was NDMA activation for In loadings below 1%. The decrease at higher loadings is interpreted as In blocking pore spaces and limiting access to Pd sites, suggesting monatomic hydrogen limitation. The only products detected were dimethylamine and ammonium with carbon and nitrogen balances in excess of 92%, consistent with a mechanism involving reductive N-N bond cleavage. Results from this study serve as a basis for optimizing bimetallic catalysts for treating NDMA contaminated waters.

  13. (Ni,Mg)3Si2O5(OH)4 solid-solution nanotubes supported by sub-0.06 wt % palladium as a robust high-efficiency catalyst for Suzuki-Miyaura cross-coupling reactions.

    PubMed

    Zhu, Wancheng; Yang, Yan; Hu, Shi; Xiang, Guolei; Xu, Biao; Zhuang, Jing; Wang, Xun

    2012-06-04

    (Ni(1-x),Mg(x))(3)Si(2)O(5)(OH)(4) solid-solution nanotubes (NTs) with tunable compositions were hydrothermally synthesized by altering the molar ratio of Mg(2+) to Ni(2+). The as-synthesized NTs were loaded with sub-0.06 wt % palladium (Pd; ∼0.045 wt %) for Suzuki-Miyaura (SM) coupling reactions between iodobenzene or 4-iodotoluene and phenylboronic acid. The (Ni,Mg)(3)Si(2)O(5)(OH)(4) (Mg(2+):Ni(2+) = 1.0:1.0) NTs supported by 0.045 wt % Pd promoted the iodobenzene-participated coupling reaction with a high yield of >99%, an excellent recycling catalytic performance during 10 cycles of catalysis with yields of ∼99%, and also an extremely low Pd releasing level of ∼0.02 ppm. High-activity Pd and PdO clusters, multitudes of dislocations, and defects and terraces contained within the NTs should contribute to the (Ni,Mg)(3)Si(2)O(5)(OH)(4) (Mg(2+):Ni(2+) = 1.0:1.0) NTs supported by 0.045 wt % Pd as a robust, reusable, and high-efficiency catalyst for SM coupling reactions with an extremely low Pd releasing level. The present hydrothermally stable (Ni,Mg)(3)Si(2)O(5)(OH)(4) (Mg(2+):Ni(2+) = 1.0:1.0) solid-solution silicate NTs provided an ideal alternative tubular-structured support for noble- or transition-metal catalysts with low Pd loading, good recycling, and extremely low ppb levels of Pd release, which could also be extended to some other SM coupling reactions.

  14. Palladium-Catalyzed, tert-Butyllithium-Mediated Dimerization of Aryl Halides and Its Application in the Atropselective Total Synthesis of Mastigophorene A.

    PubMed

    Buter, Jeffrey; Heijnen, Dorus; Vila, Carlos; Hornillos, Valentín; Otten, Edwin; Giannerini, Massimo; Minnaard, Adriaan J; Feringa, Ben L

    2016-03-07

    A palladium-catalyzed direct synthesis of symmetric biaryl compounds from aryl halides in the presence of tBuLi is described. In situ lithium-halogen exchange generates the corresponding aryl lithium reagent, which undergoes a homocoupling reaction with a second molecule of the aryl halide in the presence of the palladium catalyst (1 mol %). The reaction takes place at room temperature, is fast (1 h), and affords the corresponding biaryl compounds in good to excellent yields. The application of the method is demonstrated in an efficient asymmetric total synthesis of mastigophorene A. The chiral biaryl axis is constructed with an atropselectivity of 9:1 owing to catalyst-induced remote point-to-axial chirality transfer.

  15. 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.

  16. Palladium-catalyzed carbonylative couplings of vinylogous enolates: application to statin structures.

    PubMed

    Makarov, Ilya S; Kuwahara, Takashi; Jusseau, Xavier; Ryu, Ilhyong; Lindhardt, Anders T; Skrydstrup, Troels

    2015-11-11

    The first Pd-catalyzed carbonylative couplings of aryl and vinyl halides with vinylogous enolates are reported generating products derived from C-C bond formation exclusively at the γ-position. Good results were obtained with a dienolate derivative of acetoacetate (1,3-dioxin-4-one). These transformations occurred at room temperature and importantly with only stoichiometric carbon monoxide in a two-chamber reactor. The methodology was applied to the synthesis of two members of the statin family generating the cis-3,5-diol acid motif by a γ-selective carbonylation followed by a cis-stereoselective reduction of the 3,5-dicarbonyl acid intermediates.

  17. Palladium-Catalyzed Regioselective Synthesis of 3-Arylindoles from N-Ts-Anilines and Styrenes.

    PubMed

    Youn, So Won; Ko, Tae Yun; Jang, Young Ho

    2017-06-01

    A Pd-catalyzed intermolecular oxidative annulation between N-Ts-anilines and styrenes was developed. This method offers a straightforward and robust approach to a wide range of 3-arylindoles using readily available starting materials with good functional-group tolerance and high regioselectivity and efficiency. Further elaboration of the products obtained from this process provided access to highly functionalized and structurally diverse indoles, for example, 3-(indol-3-yl)carbazoles, 1,9-dihydropyrrolo-[2,3-b]carbazoles, and 3'-aryl-3,5'-biindoles. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Asymmetric Palladium-Catalyzed Alkene Carboamination Reactions for the Synthesis of Cyclic Sulfamides.

    PubMed

    Garlets, Zachary J; Parenti, Kaia R; Wolfe, John P

    2016-04-18

    The synthesis of cyclic sulfamides by enantioselective Pd-catalyzed alkene carboamination reactions between N-allylsulfamides and aryl or alkenyl bromides is described. High levels of asymmetric induction (up to 95:5 e.r.) are achieved using a catalyst composed of [Pd2 (dba)3 ] and (S)-Siphos-PE. Deuterium-labelling studies indicate the reactions proceed through syn-aminopalladation of the alkene and suggest that the control of syn- versus anti-aminopalladation pathways is important for asymmetric induction. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. In-Depth Assessment of the Palladium-Catalyzed Fluorination of Five-Membered Heteroaryl Bromides

    PubMed Central

    2015-01-01

    A thorough investigation of the challenging Pd-catalyzed fluorination of five-membered heteroaryl bromides is presented. Crystallographic studies and density functional theory (DFT) calculations suggest that the challenging step of this transformation is C–F reductive elimination of five-membered heteroaryl fluorides from Pd(II) complexes. On the basis of these studies, we have found that various heteroaryl bromides bearing phenyl groups in the ortho position can be effectively fluorinated under catalytic conditions. Highly activated 2-bromoazoles, such as 8-bromocaffeine, are also viable substrates for this reaction. PMID:27056379

  20. In-Depth Assessment of the Palladium-Catalyzed Fluorination of Five-Membered Heteroaryl Bromides.

    PubMed

    Milner, Phillip J; Yang, Yang; Buchwald, Stephen L

    2015-10-12

    A thorough investigation of the challenging Pd-catalyzed fluorination of five-membered heteroaryl bromides is presented. Crystallographic studies and density functional theory (DFT) calculations suggest that the challenging step of this transformation is C-F reductive elimination of five-membered heteroaryl fluorides from Pd(II) complexes. On the basis of these studies, we have found that various heteroaryl bromides bearing phenyl groups in the ortho position can be effectively fluorinated under catalytic conditions. Highly activated 2-bromoazoles, such as 8-bromocaffeine, are also viable substrates for this reaction.

  1. Access to β-lactams by enantioselective palladium(0)-catalyzed C(sp3)-H alkylation.

    PubMed

    Pedroni, Julia; Boghi, Michele; Saget, Tanguy; Cramer, Nicolai

    2014-08-18

    β-Lactams are very important structural motifs because of their broad biological activities as well as their propensity to engage in ring-opening reactions. Transition-metal-catalyzed C-H functionalizations have emerged as strategy enabling yet uncommon highly efficient disconnections. In contrast to the significant progress of Pd(0)-catalyzed C-H functionalization for aryl-aryl couplings, related reactions involving the formation of saturated C(sp(3))-C(sp(3)) bonds are elusive. Reported here is an asymmetric C-H functionalization approach to β-lactams using readily accessible chloroacetamide substrates. Important aspects of this transformation are challenging C(sp(3))-C(sp(3)) and strain-building reductive eliminations to for the four-membered ring. In general, the β-lactams are formed in excellent yields and enantioselectivities using a bulky taddol phosphoramidite ligand in combination with adamantyl carboxylic acid as cocatalyst. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Palladium-Catalyzed Oxidative Arylhalogenation of Alkenes: Synthetic Scope and Mechanistic Insights

    PubMed Central

    Kalyani, Dipannita; Satterfield, Andrew D.

    2010-01-01

    This article describes the development of a Pd-catalyzed reaction for the arylhalogenation (halogen = Cl or Br) of diverse α-olefins by oxidatively intercepting Mizoroki-Heck intermediates. These transformations afford synthetically useful 1,2- and 1,1-arylhalogenated products in good yields with good to excellent selectivities that can be modulated by changing the nature of the halogenating reagent and/or the reaction conditions. The selectivity of these reactions can be rationally tuned by: (i) controlling the relative rates of oxidative functionalization versus β-hydride elimination from equilibrating PdII-alkyl species and (ii) stabilization of organometallic PdII intermediates through the formation of π-benzyl adducts. These arylhalogenations exhibit modest to excellent levels of stereospecificity, and the key carbon-halogen bond-forming step proceeds with predominant retention of stereochemistry at carbon. PMID:20515033

  3. Palladium-catalyzed amination of dichloroquinolines with adamantane-containing amines.

    PubMed

    Abel, Anton S; Averin, Alexei D; Maloshitskaya, Olga A; Savelyev, Evgenii N; Orlinson, Boris S; Novakov, Ivan A; Beletskaya, Irina P

    2013-02-06

    Pd-catalyzed amination of isomeric 2,6-, 2,8-, 4,8- and 4,7-dichloroquinolines was studied using adamantane-containing amines in which substituents at the nitrogen atom differ in bulkiness. The selectivity of the amination of 2,6-dichloroquinoline was very low, substantially better results were obtained with 2,8-dichloroquinoline, and 4,8- and 4,7-dichloroquinolines provided the best yields of the amination products. Diamination of 4,8- and 4,7-dichloroquinolines was carried out with two amines which differ strongly in the bulkiness of the alkyl group. In the majority of cases BINAP ligand was successfully applied, however, it had to be replaced with DavePhos in certain reactions when using the most sterically hindered amine as well as for the diamination reactions.

  4. Organic carbonates as alternative solvents for palladium-catalyzed substitution reactions.

    PubMed

    Schäffner, Benjamin; Holz, Jens; Verevkin, Sergey P; Börner, Armin

    2008-01-01

    Organic carbonates, such as propylene carbonate, butylene carbonate, and diethyl carbonate, were tested in the Pd-catalyzed asymmetric allylic substitution reactions of rac-1,3-diphenyl-3-acetoxy-prop-1-ene with dimethyl malonate or benzylamine as nucleophiles. Bidentate diphosphanes were used as chiral ligands. The application of monodentate phosphanes capable of self-assembling with the metal was likewise tested. In the substitution reaction with dimethyl malonate, enantioselectivities up to 98% were achieved. In the amination reaction, the chiral product was obtained with up to 83% ee. The results confirm that these "green solvents" can be advantageously used for this catalytic transformation as an alternative to those solvents usually employed which run some risk of being harmful to the environment.

  5. Silver-Free Direct Synthesis of Alkynylphosphine Oxides via spC-H/P(O)-H Dehydrogenative Coupling Catalyzed by Palladium.

    PubMed

    Zhang, Jian-Qiu; Chen, Tieqiao; Zhang, Ji-Shu; Han, Li-Biao

    2017-09-01

    A silver-free palladium-catalyzed dehydrogenative phosphorylation of terminal alkynes with hydrogen phosphine oxides has been developed. Both aromatic and aliphatic terminal alkynes including those bearing functional groups coupled readily with hydrogen phosphine oxides, producing the corresponding value-added alkynylphosphine oxides in good to excellent yields. This reaction could be easily conducted at gram scales (10 mmol) without any decrease of the reaction efficiency, showing highly potential synthetic value in organic synthesis. A plausible Pd(0)/Pd(II) mechanism is proposed.

  6. Palladium-catalyzed stereoconvergent formylation of (E/Z)-β-bromo-β-fluorostyrenes: straightforward access to (Z)-α-fluorocinnamic aldehydes and (Z)-β-fluorocinnamic alcohols.

    PubMed

    Zemmouri, Rajae; Kajjout, Mohammed; Castanet, Yves; Eddarir, Said; Rolando, Christian

    2011-10-07

    We report here the stereoconvergent formylation of (E/Z)-β-bromo-β-fluorostyrene mixtures with carbon monoxide and sodium formate catalyzed by palladium. Optimization of reaction conditions leads to the corresponding pure (Z)-α-fluorocinnamaldehydes in good yields. The reaction was extended to styrenes bearing electro-attracting or electro-donating groups. The obtained α-fluoroaldehydes were smoothly reduced to the corresponding (Z)-β-fluorocinnamic alcohol by NaBH(4). The reaction could be performed on functionalized substrates as demonstrated by the access to the glucoside of β-fluoroconiferyl alcohol, (Z)-β-fluoroconiferin, a strong inhibitor of lignin polymerization.

  7. Palladium-catalyzed direct heck arylation of dual pi-deficient/pi-excessive heteroaromatics. Synthesis of C-5 arylated imidazo[1,5-a]pyrazines.

    PubMed

    Wang, Jian-Xin; McCubbin, J Adam; Jin, Meizhong; Laufer, Radoslaw S; Mao, Yunyu; Crew, Andrew P; Mulvihill, Mark J; Snieckus, Victor

    2008-07-17

    A general and efficient synthesis of 5-aryl imidazo[1,5- a]pyrazines by palladium-catalyzed coupling of the corresponding 8-substituted derivatives with aryl halides is described. The scope of this new reaction for the imidazo[1,5- a]pyrazine ring system was explored using three readily available 8-substituted precursors, X = NH2, NMe2, and OMe, as well as 8-aryl derivatives, X = Ar'. On the basis of these results as well as studies using a deuterated derivative, a Heck-like mechanism is proposed for this transformation.

  8. Highly regioselective palladium-catalyzed direct arylation of oxazole at C-2 or C-5 with aryl bromides, chlorides, and triflates.

    PubMed

    Strotman, Neil A; Chobanian, Harry R; Guo, Yan; He, Jiafang; Wilson, Jonathan E

    2010-08-20

    Complementary palladium-catalyzed methods for direct arylation of oxazole with high regioselectivity (>100:1) at both C-5 and C-2 have been developed for a wide range of aryl and heteroaryl bromides, chlorides, iodides, and triflates. C-5 arylation is preferred in polar solvents with phosphines 5 or 6, whereas C-2 arylation is preferred by nonpolar solvents and phosphine 3. This represents the first general method for C-5 selective arylation of oxazole and should see broad applicability in the synthesis of biologically active molecules. Additionally, potential mechanisms for these two competing arylation processes are proposed on the basis of mechanistic observations.

  9. Synthesis of 2-Azulenyltetrathiafulvalenes by Palladium-Catalyzed Direct Arylation of 2-Chloroazulenes with Tetrathiafulvalene and Their Optical and Electrochemical Properties.

    PubMed

    Shoji, Taku; Araki, Takanori; Sugiyama, Shuhei; Ohta, Akira; Sekiguchi, Ryuta; Ito, Shunji; Okujima, Tetsuo; Toyota, Kozo

    2017-02-03

    Tetrathiafulvalene (TTF) derivatives with 2-azulenyl substituents 5-11 were prepared by the palladium-catalyzed direct arylation reaction of 2-chloroazulenes with TTF in good yield. Photophysical properties of these compounds were investigated by UV-vis spectroscopy and theoretical calculations. Redox behavior of the novel azulene-substituted TTFs was examined by using cyclic voltammetry and differential pulse voltammetry, which revealed their multistep electrochemical oxidation and/or reduction properties. Moreover, these TTF derivatives showed significant spectral change in the visible region under the redox conditions.

  10. 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

  11. Palladium-catalyzed difluoroalkylation of aryl boronic acids: a new method for the synthesis of aryldifluoromethylated phosphonates and carboxylic acid derivatives.

    PubMed

    Feng, Zhang; Min, Qiao-Qiao; Xiao, Yu-Lan; Zhang, Bo; Zhang, Xingang

    2014-02-03

    The palladium-catalyzed difluoroalkylation of aryl boronic acids with bromodifluoromethylphosphonate, bromodifluoroacetate, and further derivatives has been developed. This method provides a facile and useful access to a series of functionalized difluoromethylated arenes (ArCF2 PO(OEt)2 , ArCF2 CO2 Et, and ArCF2 CONR(1) R(2) ) that have important applications in drug discovery and development. Preliminary mechanistic studies reveal that a single electron transfer (SET) pathway may be involved in the catalytic cycle.

  12. Cobryketone derived from vitamin B12 via palladium-catalyzed cleavage of the sp3-sp3 carbon-carbon bond.

    PubMed

    Kurcoń, Sylwester; Proinsias, Keith ó; Gryko, Dorota

    2013-04-19

    Heptamethyl cobyrinate was transformed into hexamethyl 8-nor-cobyrinate. The crucial step involved the synthesis of new, vitamin B12 derived cobryketone via palladium-catalyzed cleavage of the sp(3)-sp(3) carbon-carbon bond with the liberation of the ketone. The replacement of sp(3) carbon atom with sp(2) (C═O) at the 8-position produces a bathochromic shift of all absorption bands and makes α and β bands equal as a consequence of the expansion of the existing conjugated system of double bonds.

  13. Palladium-catalyzed addition of potassium aryltrifluoroborates to aliphatic nitriles: synthesis of alkyl aryl ketones, diketone compounds, and 2-arylbenzo[b]furans.

    PubMed

    Wang, Xingyong; Liu, Miaochang; Xu, Long; Wang, Qingzong; Chen, Jiuxi; Ding, Jinchang; Wu, Huayue

    2013-06-07

    A palladium-catalyzed addition of potassium aryltrifluoroborates to aliphatic nitriles has been developed, leading to a wide range of alkyl aryl ketones with moderate to excellent yields. Moreover, several dinitriles (e.g., malononitrile, glutaronitrile, and adiponitrile) were applicable to this process for the construction of 1,3-, 1,5-, or 1,6-dicarbonyl compounds. The scope of the developed approach is successfully explored toward the one-step synthesis of 2-arylbenzo[b]furans via sequential addition and intramolecular annulation reactions. The methodology accepted a wide range of substrates and is applicable to library synthesis.

  14. Regioselective palladium-catalyzed ring-opening reactions of C1-substituted oxabicyclo[2,2,1]hepta-2,5-diene-2,3-dicarboxylates

    PubMed Central

    Edmunds, Michael; Raheem, Mohammed Abdul; Boutin, Rebecca; Tait, Katrina

    2016-01-01

    Summary Palladium-catalyzed ring-opening reactions of C1 substituted 7-oxanorbornadiene derivatives with aryl iodides were investigated. The optimal conditions for this reaction were found to be PdCl2(PPh3)2, ZnCl2, Et3N and Zn in THF. Both steric and electronic factors played a role in the outcome of the reaction as increasing the steric bulk on the bridgehead carbon decreased the yield. These reactions were found to be highly regioselective, giving only one of the two possible regioisomers in all cases. A diverse collection of novel, highly substituted biphenyl derivatives were obtained. PMID:26977182

  15. 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.

  16. Palladium(II)‐Catalyzed Synthesis of Sulfinates from Boronic Acids and DABSO: A Redox‐Neutral, Phosphine‐Free Transformation

    PubMed Central

    Deeming, Alex S.; Russell, Claire J.

    2015-01-01

    Abstract A redox‐neutral palladium(II)‐catalyzed conversion of aryl, heteroaryl, and alkenyl boronic acids into sulfinate intermediates, and onwards to sulfones and sulfonamides, has been realized. A simple Pd(OAc)2 catalyst, in combination with the sulfur dioxide surrogate 1,4‐diazabicyclo[2.2.2]octane bis(sulfur dioxide) (DABSO), is sufficient to achieve rapid and high‐yielding conversion of the boronic acids into the corresponding sulfinates. Addition of C‐ or N‐based electrophiles then allows conversion into sulfones and sulfonamides, respectively, in a one‐pot, two‐step process. PMID:26596861

  17. Palladium-Catalyzed Decarbonylative Dehydration for the Synthesis of α-Vinyl Carbonyl Compounds and Total Synthesis of (−)-Aspewentin A, B, and C

    PubMed Central

    Liu, Yiyang; Virgil, Scott C.; Grubbs, Robert H.; Stoltz, Brian M.

    2015-01-01

    The direct α-vinylation of carbonyl compounds that forms a quaternary stereocenter is a challenging transformation. We discovered that δ-oxocarboxylic acids can serve as masked vinyl compounds and be unveiled by palladium-catalyzed decarbonylative dehydration. The carboxylic acids are readily available through enantioselective acrylate addition or asymmetric allylic alkylation. A variety of α-vinyl quaternary carbonyl compounds are obtained in good yields, and an application in the first enantioselective total synthesis of (−)-aspewentin A, B, and C is demonstrated. PMID:26230413

  18. Transition-metal-free Sonogashira-type cross-coupling of alkynes with fluoroarenes.

    PubMed

    Jin, Guanyi; Zhang, Xuxue; Cao, Song

    2013-06-21

    A novel, inexpensive, and efficient palladium-, copper-, ligand-, and amine-free Sonogashira-type cross-coupling reaction of terminal alkynes with unreactive aryl fluorides in the presence of sodium, sodium methoxide, and calcium hydroxide under the assistance of a Grignard reagent was developed. A plausible mechanism was also suggested.

  19. 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.

  20. Relative reactivity of alkenyl alcohols in the palladium-catalyzed redox-relay Heck reaction.

    PubMed

    Hilton, Margaret J; Cheng, Bin; Buckley, Benjamin R; Xu, Liping; Wiest, Olaf; Sigman, Matthew S

    2015-09-16

    The relative rates of alkenyl alcohols in the Pd-catalyzed redox-relay Heck reaction were measured in order to examine the effect of their steric and electronic properties on the rate-determining step. Competition experiments between an allylic alkenyl alcohol and two substrates with differing chain lengths revealed that the allylic alcohol reacts 3-4 times faster in either case. Competition between di- and trisubstituted alkenyl alcohols provided an interesting scenario, in which the disubstituted alkene was consumed first followed by reaction of the trisubstituted alkene. Consistent with this observation, the transition structures for the migratory insertion of the aryl group into the di- and trisubstituted alkenes were calculated with a lower barrier for the former. An internal competition between a substrate containing two alcohols with differing chain lengths demonstrated the catalyst's preference for migrating towards the closest alcohol. Additionally, it was observed that increasing the electron density in the arene boronic acid promotes a faster reaction, which correlates with Hammett σp values to give a ρ of -0.87.

  1. Synthesis of styrenes by palladium(II)-catalyzed vinylation of arylboronic acids and aryltrifluoroborates by using vinyl acetate.

    PubMed

    Lindh, Jonas; Sävmarker, Jonas; Nilsson, Peter; Sjöberg, Per J R; Larhed, Mats

    2009-01-01

    One Heck of a reaction: Treatment of arylboronic acids or aryltrifluoroborates with vinyl acetate by using a palladium(II) catalyst gives the corresponding styrenes (see scheme). No palladium reoxidant is needed and the vinylation is performed under non-inert conditionsReactions of aromatic and heteroaromatic boronic acids or aryltrifluoroborate salts with vinyl acetate in the presence of a palladium(II) catalyst give the corresponding styrenes in good yields. This Heck reaction proceeds with microwave heating in less than 30 min at 140 degrees C in the absence of base and tolerates a variety of substituents. No palladium reoxidant is needed and the vinylation is performed under non-inert conditions. Mass spectrometry (electrospray ionization mass spectrometry (ESIMS) and tandem mass spectrometry (MS/MS)) was used to identify cationic palladium-containing complexes in ongoing reactions. The key intermediates that have been detected, together with experiments that used deuterated vinyl acetate, support the existence of catalytically active palladium hydride species, and that it is the arylation of ethylene, not vinyl acetate, which generates the styrene product. The mechanism of the reaction is discussed in terms of the palladium(II) intermediates mentioned above.

  2. Efficient Decarbonylation of Furfural to Furan Catalyzed by Zirconia-Supported Palladium Clusters with Low Atomicity.

    PubMed

    Ishida, Tamao; Kume, Kurumi; Kinjo, Kota; Honma, Tetsuo; Nakada, Kengo; Ohashi, Hironori; Yokoyama, Takushi; Hamasaki, Akiyuki; Murayama, Haruno; Izawa, Yusuke; Utsunomiya, Masaru; Tokunaga, Makoto

    2016-12-20

    Decarbonylation of furfural to furan was efficiently catalyzed by ZrO2 -supported Pd clusters in the liquid phase under a N2 atmosphere without additives. Although Pd/C and Pd/Al2 O3 have frequently been used for decarbonylation, Pd/ZrO2 exhibited superior catalytic performance compared with these conventional catalysts. Transmission electron microscopy and X-ray absorption fine structure measurements revealed that the size of the Pd particles decreased with an increase in the specific surface area of ZrO2 . ZrO2 with a high surface area immobilized Pd as clusters consisting of several (three to five) Pd atoms, whereas Pd aggregated to form nanoparticles on other supports such as carbon and Al2 O3 despite their high surface areas. The catalytic activity of Pd/ZrO2 was enhanced with a decrease in particle size, and the smallest Pd/ZrO2 was the most active catalyst for decarbonylation. When CeO2 was used as the support, a decrease in Pd particle size with an increase in surface area was also observed. Single Pd atoms were deposited on CeO2 with a high surface area, with a strong interaction through the formation of a Pd-O-Ce bond, which led to a lower catalytic activity than that of Pd/ZrO2 . This result suggests that zero-valent small Pd clusters consisting of more than one Pd atom are the active species for the decarbonylation reaction. Recycling tests proved that Pd/ZrO2 maintained its catalytic activity until its sixth use. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Synthesis and antituberculosis activity of novel 5-styryl-4-(hetero)aryl-pyrimidines via combination of the Pd-catalyzed Suzuki cross-coupling and S(N)(H) reactions.

    PubMed

    Kravchenko, Marionella A; Verbitskiy, Egor V; Medvinskiy, Igor D; Rusinov, Gennady L; Charushin, Valery N

    2014-07-15

    Combination of the Suzuki cross-coupling and nucleophilic aromatic substitution of hydrogen (SN(H)) reactions proved to be a convenient method for the synthesis of 5-styryl-4-(hetero)aryl substituted pyrimidines from commercially available 5-bromopyrimidine. All intermediate 5-bromo-4-(hetero)aryl substituted pyrimidines and also the targeted 5-styryl-4-(hetero)arylpyrimidines were found to be active in micromolar concentrations in vitro against Mycobacterium tuberculosis H37Rv, avium, terrae, and multi-drug-resistant strain isolated from tuberculosis patients in Ural region (Russia). It has been found that some of these compounds possess a low toxicity and have a bacteriostatic effect, comparable and even higher with that of first-line antituberculosis drugs. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Microwave-enhanced cross-coupling reactions involving alkynyltrifluoroborates with aryl bromides.

    PubMed

    Coltuclu, Vitali; Dadush, Eric; Naravane, Abhijit; Kabalka, George W

    2013-01-29

    Palladium-catalyzed alkynylation has emerged as one of the most reliable methods for the synthesis of alkynes which are often used in natural product syntheses and material science. An efficient method for coupling alkynyltrifluoroborates with various aryl bromides in the presence of a palladium catalyst has been developed using microwave irradiation. The microwave reactions are rapid and efficient.

  5. Three-step synthesis of 2,5,7-trisubstituted indoles from N-acetyl-2,4,6-trichloroaniline using Pd-catalyzed site-selective cross-coupling.

    PubMed

    Yamaguchi, Miyuki; Manabe, Kei

    2017-08-09

    We report a facile three-step synthesis of 2,5,7-trisubstituted indoles from N-acetyl-2,4,6-trichloroaniline, with the first step featuring Pd/dihydroxyterphenylphosphine (DHTP)-catalyzed ortho-selective Sonogashira coupling followed by cyclization to afford 2-substituted 5,7-dichloroindoles. Subsequent introduction of aryl or alkenyl groups at the C7 position was achieved by Pd/DHTP-catalyzed site-selective Kumada-Tamao-Corriu coupling, with further substitution of the chlorine at the C5 position (Suzuki-Miyaura coupling or Buchwald-Hartwig amination) affording 2,5,7-trisubstituted indoles.

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

    DOE PAGES

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

    2015-02-05

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

  7. 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.

  8. A facile route to 5-methyl-5H-indeno[1,2-c]quinolones via palladium-catalyzed cyclization of 2-alkynylbromobenzenes with N,N-dimethyl-2-alkynylanilines.

    PubMed

    Pan, Xiaolin; Luo, Yong; Kuang, Yunyan; Li, Guangming

    2014-08-21

    A tandem reaction catalyzed by palladium is developed to provide a facile and simple route for the synthesis of 5-methyl-5H-indeno[1,2-c]quinolones, which can introduce diversity and complexity into the products from readily available starting materials. This transformation proceeds well with good functional group tolerance.

  9. Raising the pKa Limit of “Soft” Nucleophiles in Palladium-Catalyzed Allylic Substitutions. Application of Diarylmethane Pronucleophiles

    PubMed Central

    Sha, Sheng-Chun; Zhang, Jiadi; Carroll, Patrick J.

    2013-01-01

    The Tsuji-Trost allylic substitution reaction provides a useful and efficient approach to construct C-C bonds between sp3-hybridized carbons. The widely accepted paradigm for classifying the mode of attack of nucleophiles on palladium π-allyl intermediates in the Tsuji-Trost reaction is based on the pKa of the pronucleophile: (1) stabilized or “soft” carbon nucleophiles and heteroatom nucleophiles (e.g., pronucleophiles with pKa’s < 25), and (2) unstabilized or “hard” nucleophiles (those from pronucleophiles with pKa’s > 25). One of the keys to the continuing development of allylic substitution processes remains broadening the scope of “soft” nucleophiles. Herein we report a general method for the room temperature Pd-catalyzed allylic substitution with diarylmethane derivatives (pKa’s up to 32). The synthetic significance of the method is that it provides a rapid access to products containing allylated diarylmethyl motifs. The method is general for a wide range of nucleophiles derived from diarylmethanes and heterocyclic derivatives. A procedure for the Pd-catalyzed allylic substitutions to afford diallylation products with quaternary centers is also described. With triarylmethanes and, alkylated diarylmethanes the corresponding allylated products are isolated. We anticipate that the described method will be a valuable complement to the existing arsenal of nucleophiles in Pd-catalyzed allylic substitutions. Mechanistic studies show that the nucleophile derived from diphenylmethane undergoes external attack on π-allyl palladium species under our reaction conditions. This unexpected observation indicates that diarylmethane derivatives behave as “soft” or stabilized nucleophiles. The results of this study indicate that the cutoff between “soft” and “hard” nucleophiles should be raised from a pronucleophile pKa of 25 to at least 32. PMID:24147620

  10. Partial Hydrogenation of Sunflower Oil-derived FAMEs Catalyzed by the Efficient and Recyclable Palladium Nanoparticles in Polyethylene Glycol.

    PubMed

    Liu, Wei; Lu, Guanghui

    2017-10-01

    One approach to improve the oxidative stability of biodiesel is the partial hydrogenation of carbon-carbon double bonds. In the current work, an efficient catalytic system using Pd(OAc)2 dissolved in polyethylene glycol (PEG) which in situ generates palladium nanoparticles was developed in order to promote a selective partial hydrogenation reaction of sunflower oil FAMEs into mono-hydrogenated products avoiding the formation of saturated compounds or trans-isomers. High content of methyl oleate (85.0±1.4%) was obtained by hydrogenation of sunflower oil biodiesel with only 7.0±0.2% stearic acid. Through evaluating the palladium nanoparticles by TEM analysis, it is observed that 4 nm palladium nanoparticles generated in situ in PEG4000 are highly selective for the partial hydrogenation of sunflower oil biodiesel. And the Pd-PEG4000 catalyst can be resued for five times without obvious loss of activity or methyl oleate selectivity.

  11. Cu(i)/Fe(iii)-Catalyzed C-P cross-coupling of styrenes with H-phosphine oxides: a facile and selective synthesis of alkenylphosphine oxides and β-ketophosphonates.

    PubMed

    Gu, Jian; Cai, Chun

    2017-05-16

    Cu(i)/Fe(iii)-Catalyzed phosphorylation and oxyphosphorylation of styrenes with H-phosphonates which can be controlled by varying the reaction temperature are developed. This study offers a new and expedient strategy for the synthesis of useful alkenylphosphine oxides and β-ketophosphonates in satisfactory yields. Moreover, the transformation is proposed to proceed via a radical process and exhibits a broad substrate scope and good functional group tolerance.

  12. Regio- and stereoselective palladium-pincer complex catalyzed allylation of sulfonylimines with trifluoro(allyl)borates and allylstannanes: a combined experimental and theoretical study.

    PubMed

    Wallner, Olov A; Szabó, Kálmán J

    2006-09-06

    Regio- and stereoselective palladium-pincer complex catalyzed allylation of sulfonylimines has been performed by using substituted trifluoro(allyl)borates and trimethylallylstannanes. The reactions provide the corresponding branched allylic products with excellent regioselectivity. The stereoselectivity of these processes is very high when trifluoro(cinnamyl)borate and trimethyl cinnamyl stannane are employed as allylic precursors; however, the reaction with trifluoro(crotyl)borate results in poor stereoselectivity. The major diastereomer formed in these reactions was the syn isomer, while the (previously reported) reactions with aldehyde electrophiles afforded the anti products, indicating that the mechanism of the stereoselection is dependent on the applied electrophile. Therefore, we have studied the mechanistic aspects of the allylation reactions by experimental studies and DFT modeling. The experimental mechanistic studies have clearly shown that potassium trifluoro(allyl)borate undergoes transmetallation with palladium-pincer complex 1 a affording an eta(1)-allylpalladium-pincer complex (1 e). The mechanism of the transfer of the allyl moiety from palladium to the sulfonylimine substrate was studied by DFT calculations at the B3PW91/LANL2DZ+P level of theory. These calculations have shown that the electrophilic substitution of sulfonylimines proceeds in a one-step process with a relatively low activation energy. The topology of the potential energy surface in the vicinity of the transition-state structure proved to be rather complicated as nine different geometries with similar energies were located as first order saddle points. Our studies have also shown that the high stereoselectivity with cinnamyl metal reagents stems from steric interactions in the TS structure of the allylation reaction. In addition, these studies have revealed that the mechanism of the stereoselection in the allylation of aldehydes and sulfonylimines is fundamentally different.

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

    DOE PAGES

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

    2015-01-01

    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.

  14. Palladium-catalyzed microwave-assisted direct arylation of imidazo[2,1-b]thiazoles with aryl bromides: synthesis and mechanistic study.

    PubMed

    Zhu, Yi-Shuo; Shi, Benyi; Fang, Ran; Wang, Xiaoxuan; Jing, Huanwang

    2014-08-14

    A palladium-catalyzed direct C-H arylation of various imidazo[2,1-b]thiazoles with a range of aryl bromides under microwave irradiation is described. 6-Phenyl substituted imidazo[2,1-b]thiazoles could be regioselectively C-5 arylated using the developed protocol. The utility of this method enables the representative coupling product to be achieved by a sequential one-pot reaction. Density functional theory (DFT) calculations show that this arylation proceeds via a concerted metalation-deprotonation (CMD) pathway, which is in agreement with our experimental results. This work provides a convenient access to a variety of biologically active imidazo[2,1-b]thiazole derivatives. Also, it enriches the mechanism study of site-selective C-H arylation in fused heterocycles, and offers a valuable guide to design highly efficient catalytic systems for the preparation of similar compounds.

  15. The Development of Versatile Methods for Palladium-Catalyzed Coupling Reactions of Aryl Electrophiles Through the Use of P(t-Bu)3 and PCy3 as Ligands

    PubMed Central

    FU, GREGORY C.

    2009-01-01

    CONSPECTUS Metal-catalyzed coupling reactions of aryl electrophiles with organometallics and with olefins serve as unusually effective tools for forming new carbon-carbon bonds. By 1998, researchers had developed catalysts that achieved reactions of aryl iodides, bromides, and triflates. Nevertheless, many noteworthy challenges remained, among them: couplings of aryl iodides, bromides, and triflates under mild conditions (at room temperature, for example); couplings of hindered reaction partners; and, couplings of inexpensive aryl chlorides. This Account highlights some of the progress that has been made over the past decade, largely through the appropriate choice of ligand, in achieving these synthetic objectives. In particular, we have established that palladium in combination with a bulky trialkylphosphine accomplishes a broad spectrum of coupling processes, including Suzuki, Stille, Negishi, and Heck reactions. These methods have been applied in a wide array of settings, such as natural-product synthesis, materials science, and bioorganic chemistry. PMID:18947239

  16. Rapid Access to 2,2'-Bithiazole-Based Copolymers via Sequential Palladium-Catalyzed C-H/C-X and C-H/C-H Coupling Reactions.

    PubMed

    Guo, Qiang; Jiang, Ruyong; Wu, Di; You, Jingsong

    2016-05-01

    A rapid access to 2,2'-bithiazole-based copolymers has been developed on the basis of the sequential palladium-catalyzed CH/CX and CH/CH coupling reactions. To assemble a "copolymer" through homopolymerization, a type of symmetric A-B-A-type building block is designed as the monomer and prepared via the regioselective C5H arylation of thiazole. A PdCl2 /CuCl-cocatalyzed oxidative CH/CH homopolymerization has been established to afford the 2,2'-bithiazole-based copolymers with high Mn (up to 69400). The current protocol features atom- and step-economy and exhibits a potential in the highly efficient construction of conjugated copolymers.

  17. Merging C-H activation and alkene difunctionalization at room temperature: a palladium-catalyzed divergent synthesis of indoles and indolines.

    PubMed

    Manna, Manash Kumar; Hossian, Asik; Jana, Ranjan

    2015-02-06

    A palladium-catalyzed 1,2-carboamination through C-H activation at room temperature is reported for the synthesis of 2-arylindoles, and indolines from readily available, inexpensive aryl ureas and vinyl arenes. The reaction initiates with a urea-directed electrophilic ortho palladation, alkene insertion, and β-hydride elimination sequences to provide the Fujiwara-Moritani arylation product. Subsequently, aza-Wacker cyclization, and β-hydride elimination provide the 2-arylindoles in high yields. Intercepting the common σ-alkyl-Pd intermediate, corresponding indolines are also achieved. The indoline formation is attributed to the generation of stabilized, cationic π-benzyl-Pd species to suppress β-hydride elimination.

  18. 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.

  19. Palladium-Catalyzed Directed C(sp(3))-H Arylation of Saturated Heterocycles at C-3 Using a Concise Optimization Approach.

    PubMed

    Affron, Dominic P; Bull, James A

    2016-01-01

    Saturated heterocycles, such as THFs, pyrrolidines, piperidines and THPs, are essential components of many biologically active compounds. Examples of C-H functionalization on these important ring systems remain scarce, especially at unactivated positions. Here we report the development of conditions for the palladium-catalyzed stereoselective C(sp(3))-H arylation at unactivated 3-positions of 5- and 6-membered N- and O-heterocycles with aminoquinoline directing groups. Subtle differences in substrate structures altered their reactivity significantly; and different conditions were required to achieve high yields in each case. Successful conditions were developed using a short empirical optimization approach to cover reaction space with a limited set of variables. Excellent cis-selectivity was achieved in all cases, except for the THP substrate where minor trans-products were formed through a different palladacyclic intermediate. Here, differences in reactivity and selectivity with other directing groups were examined.

  20. Development of Stereocontrolled Palladium(II)-Catalyzed Domino Heck/Suzuki β,α-Diarylation Reactions with Chelating Vinyl Ethers and Arylboronic Acids.

    PubMed

    Trejos, Alejandro; Odell, Luke R; Larhed, Mats

    2012-02-01

    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.