From Established to Emerging: Evolution of Cross-Coupling Reactions

InfoMetricsFiguresRef. The Journal of Organic ChemistryVol 89/Issue 22Article This publication is free to access through this site. Learn More CiteCitationCitation and abstractCitation and referencesMore citation options ShareShare onFacebookX (Twitter)WeChatLinkedInRedditEmailJump toExpandCollapse EditorialNovember 15, 2024From Established to Emerging: Evolution of Cross-Coupling ReactionsClick to copy article linkArticle link copied!Mark R. BiscoeMark R. BiscoeDepartment of Chemistry and Biochemistry, The City College of New York (CCNY), New York, New York 10031, United StatesThe Graduate Center of the City University of New York (CUNY), 365 Fifth Avenue, New York, New York 10016, United StatesMore by Mark R. Biscoehttps://orcid.org/0000-0003-1257-6288Josep CornellaJosep CornellaMax-Planck-Institut für Kohlenforschung, Kaiser-Wilhelm-Platz 1, 45470, Mülheim an der Ruhr, GermanyMore by Josep Cornellahttps://orcid.org/0000-0003-4152-7098Dipannita KalyaniDipannita KalyaniDiscovery Chemistry, Merck & Co., Inc., Rahway, New Jersey 07065, United StatesMore by Dipannita Kalyanihttps://orcid.org/0000-0003-4349-8016Sharon Neufeldt*Sharon NeufeldtDepartment of Chemistry and Biochemistry, Montana State University, Bozeman, Montana 59717, United States*[email protected]More by Sharon Neufeldthttps://orcid.org/0000-0001-7995-3995Open PDFThe Journal of Organic ChemistryCite this: J. Org. Chem. 2024, 89, 22, 16065–16069Click to copy citationCitation copied!https://pubs.acs.org/doi/10.1021/acs.joc.4c02573https://doi.org/10.1021/acs.joc.4c02573Published November 15, 2024 Publication History Received 17 October 2024Published online 15 November 2024Published in issue 15 November 2024editorialCopyright © Published 2024 by American Chemical Society. This publication is available under these Terms of Use. Request reuse permissionsThis publication is licensed for personal use by The American Chemical Society. ACS PublicationsCopyright © Published 2024 by American Chemical SocietySubjectswhat are subjectsArticle subjects are automatically applied from the ACS Subject Taxonomy and describe the scientific concepts and themes of the article.AlkylsCross coupling reactionElectrophilesOrganometallic reactionsSubstitution reactionsSPECIAL ISSUEThis article is part of the Next-Generation Cross-Coupling Chemistry special issue.The construction of bonds between C atoms and biologically relevant elements such as C, O, N, S, and P (among others) is a fundamental goal of synthetic organic chemists. Despite early advances in C–C bond forming reactions (e.g., aldol chemistry, reactions of Grignard reagents), in the 1960s a key challenge remained: the efficient construction of C–C bonds between two C(sp2) atoms (Figure 1A). By the late 1970s, the work of multiple chemists converged on a solution involving the coupling of alkenes or aryl nucleophiles derived from main group organometallic species [C(sp2)–M; M = B, Sn, Zn, or Mg] with aryl electrophiles [C(sp2)–X; X = I, Br, Cl, OTf] in the presence of a Ni or Pd catalyst. (1−8) With these discoveries, a new paradigm for the formation of chemical bonds emerged. The importance and impact of the C–C cross-coupling reaction catapulted it to a venerable place in the field of synthesis, together with amide bond formation and nucleophilic substitution. (9) In 2010, the Nobel Prize in Chemistry was awarded to contributors who spearheaded this revolution, namely, Akira Suzuki, Ei-ichi Negishi, and Richard F. Heck. (10)Figure 1Figure 1. (A) Pd-catalyzed cross-coupling reaction. (B) Canonical mechanism of cross-couplings involving organometallic nucleophiles.High Resolution ImageDownload MS PowerPoint SlideAlthough the origin of the term "cross-coupling" is commonly associated with the development of the Suzuki–Miyaura, Stille, Kumada, and Negishi reactions (named after their inventors), earlier examples existed from Glaser, (11) Ullman, (12) or Kharasch (13) involving reactions between organometallic reagents and aryl halides catalyzed by transition metal salts. However, the low selectivity and yields and the lack of mechanistic understanding limited the widespread adoption of such strategies. On the other hand, Pd-catalyzed cross-coupling reactions offered high yields, broadened substrate scope, and the possibility to isolate and study stable organometallic intermediates. Over the years, numerous mechanistic investigations of transition-metal-catalyzed cross-coupling reactions have appeared in the literature. Based on these studies, the community reached an agreement that the catalytic manifold for cross-couplings involving organometallic nucleophiles includes three main organometallic steps: oxidative addition, transmetalation, and reductive elimination (Figure 1B). Although each mechanistic step has its own intricacies and complications, this general picture has served organic chemists as a guiding principle by which to understand and predict reactivity, selectivity, and other features to advance the field of cross-coupling.From the continuous evolution of cross-coupling strategies, a dizzying diversity of mechanisms, reagent classes, and product structures characterizes modern cross-couplings. As these reactions stray from the traditional characteristics of canonical cross-couplings, the term "cross-coupling" has evolved to represent a synthetic philosophy rather than a mechanistic or reactant-bound definition. (14) In a general sense, cross-coupling reactions can be simply illustrated as merging two (or more) building blocks together to construct new bond(s). The reactions are mediated by a third party, an entity that is traditionally a transition metal catalyst, but is occasionally very different (e.g., photons, (15) a main group element (16)). Reactions that cannot be easily placed into a different well-defined category can often be good candidates for inclusion in the broader "cross-coupling" framework.Inspired by the creative reports in this Special Issue, here we attempt to identify some of the research themes that have characterized the field of cross-coupling. Along the left side of the timeline in Figure 2, points are marked to indicate seminal publication(s) for each theme. (1,3,10−12,17−33) In more ambiguous cases, landmark publications were chosen based on the resemblance between the products and those of canonical cross-couplings. For example, Périchon's synthesis of biaryls in 1993 was selected to represent the beginning of the era of electrochemical cross-coupling. (24) For many themes, multiple years─or even decades─passed before a relative flurry of activity on the theme began to appear in the literature. The points along the right side of the timeline represent some publications that contributed to the inflection period in popularity of a theme. (2,4−8,13,34−48) For brevity, we selected a minimal number of examples, but this list of key contributions is certainly incomplete and numerous other papers represent important strides within the research areas. Many of the reports in this Special Issue fall into one or more of the research themes illustrated in the timeline. Other articles, such as those by Li and Sun (DOI: 10.1021/acs.joc.3c02417), Lv and Li (DOI: 10.1021/acs.joc.3c00744), Shenvi (DOI: 10.1021/acs.joc.4c00260), and co-workers, branch out even further and highlight the idea of cross-coupling as a synthetic philosophy.Figure 2Figure 2. Timeline of selected research themes in the area of cross-coupling (XC): seminal work (left side) and approximate inflection periods (right side).High Resolution ImageDownload MS PowerPoint SlideWhile cross-coupling reactions were initially largely dominated by the use of aryl iodides and bromides, the desire to broaden the scope to include more challenging electrophiles, such as Ar–Cl and phenolic derivatives like Ar–OTs and Ar–OMs, sparked innovations in ligand design and in Ni-catalyzed cross-couplings. Since the original reports from Wenkert demonstrating Ni-catalyzed Kumada cross-couplings with Ar–OMe and Ar–OCOR, (20) a diversity of methods have been reported for employing challenging electrophiles, typically mediated by highly nucleophilic Ni catalysts (44) or by Pd supported by bulky ligands. In this issue, reports by Johnson and Stradiotto (DOI: 10.1021/acs.joc.3c01584) and by Szostak (DOI: 10.1021/acs.joc.4c00103) represent examples of cross-couplings that involve activation of strong bonds. As more classes of electrophiles have become viable coupling partners for cross-coupling reactions, issues of chemo- and site-selectivity needed to be addressed, (28,45) as exemplified in a report by So et al. (DOI: 10.1021/acs.joc.3c02345).Fundamental mechanistic studies on single organometallic catalytic steps, such as an article in this issue from Denmark et al. (DOI: 10.1021/acs.joc.3c02629), continue to fuel advances in cross-couplings. Concurrent with establishment of the canonical mechanism in Figure 1B, Heck and Sonogashira cross-couplings emerged, illustrating that deviations from the standard pathway are also possible. (1,2,19,38) These mechanistic variations spurred the creativity of synthetic chemists, resulting in several modifications of the classical cross-coupling paradigm. For example, replacing prefunctionalized nucleophiles with simple C–H nucleophiles has led to a major revolution in the field of organic synthesis. (22,40) A contribution in this issue by Hruszkewycz, Leitch, and co-workers exploits this theme for the direct alkenylation of heterocycles (DOI: 10.1021/acs.joc.3c02311). Even more drastic deviations from the canonical mechanism have arisen from the recognition that cross-coupling can be achieved through single-electron transfer (SET) chemistry. Such processes perhaps represent one of the most active research areas in cross-coupling currently, and can be achieved through chemical, photochemical, or electrochemical methods. In this Special Issue, a majority of manuscripts fit into one of these themes characterized by radical species, including Perspectives by Bahamonde (DOI: 10.1021/acs.joc.3c02353), Gesmundo (DOI: 10.1021/acs.joc.3c02351), and co-workers.Though early studies of metal-catalyzed cross-coupling reactions focused on the formation of C(sp2)–C(sp2) bonds, successful incorporation of C(sp3) nucleophiles and electrophiles into cross-coupling methods has more recently enabled researchers to develop a broad array of strategies to elaborate three-dimensional organic molecules via C(sp3)–C(sp2) or C(sp3)–C(sp3) bond-forming processes. (17,25,36,43) To circumvent the inherent challenge of alkyl transmetalation and oxidative addition, the development of new approaches to efficiently transfer alkyl groups to transition metal catalysts is required. Because alkyl nucleophiles and alkyl electrophiles can each be incorporated into the catalytic cycle via one-electron or two-electron mechanisms, a wide array of cross-coupling approaches can be envisioned using a variety of transition metal catalysts and cross-coupling mediators. Modern strategies capitalizing on SET mechanisms have been particularly impactful in facilitating the development of new C(sp3)–C(sp2) and C(sp3)–C(sp3) bond-forming reactions. Collectively, these new approaches are well represented in the current issue where numerous cross-coupling studies feature reactions involving at least one alkyl partner. In this Special Issue, Denmark (DOI: 10.1021/acs.joc.4c00089) describes a Pd-catalyzed C(sp3)–C(sp2) bond-forming Suzuki–Miyaura reaction involving primary alkylboronic esters that undergo transmetalation via a two-electron mechanism. Noël and Watson each report studies involving the use of Ni-catalyzed alkyl deamination to access alkyl radicals for use in cross-coupling reactions. Noël (DOI: 10.1021/acs.joc.3c00859) incorporates alkyl groups into a Ni-catalyzed cross-electrophile reaction via a SET deamination pathway enabled by electrocatalysis. In contrast, Watson (DOI: 10.1021/acs.joc.3c00665) employs a Ni-catalyzed approach that selectively couples alkylzinc nucleophiles with alkyl partners generated by deamination. Both Waldvogel and Rousseaux describe new Ni-catalyzed cross-coupling reactions in which generation of alkyl radicals is achieved through the use of redox-active esters. Waldvogel (DOI: 10.1021/acs.joc.4c00428) combines Ni catalysis and electrocatalysis to generate primary alkyl radicals from redox-active esters for use in the synthesis of sitagliptin. Rousseaux (DOI: 10.1021/acs.joc.3c02354) employs reductive Ni-catalyzed cross-coupling of redox-active esters and aryl iodides for the preparation of α-aryl nitriles. The works of Xiao, Shen, and Roberts all engage alkyl radicals in cross-coupling reactions through the merger of transition metal catalysis and visible light catalysis. In the work of Xiao (DOI: 10.1021/acs.joc.3c02348), tertiary alkyl radicals are generated photocatalytically from alkylgermanium nucleophiles and incorporated into subsequent Ni-catalyzed acylation reactions. Shen (DOI: 10.1021/acs.joc.3c02293) merges Ni-catalysis and photocatalysis in a stereoconvergent reductive coupling that enables the formation of highly enantioenriched benzylic alcohols. Roberts (DOI: 10.1021/acs.joc.3c00872), in a conceptually novel approach to the formation of alkyl radicals, merges alkyl decarboxylation and alkyl desulfonylation in a photocatalyzed Cu-mediated cross-coupling approach toward benzylic trifluoromethylation. Finally, Giri (DOI: 10.1021/acs.joc.3c02548) describes a process for the dibenzylation of styrenes that proceeds via the iron-promoted formation of benzylic radicals.SET pathways are also useful for next-generation cross-couplings not involving alkyl coupling partners. For example, in this issue Li, Sun, and Ding (DOI: 10.1021/acs.joc.4c00021) employ electrochemical cross-coupling to access biaryl products. Kakiuchi (DOI: 10.1021/acs.joc.3c02601) describes the use of electrochemistry in combination with palladium catalysis to achieve C–H iodination.Alongside the evolution of diverse paradigms, new technologies such as High-Throughput Experimentation (HTE) emerged to best leverage the potential of cross-couplings. (29,49) HTE has become a mainstay in process and medicinal chemistry campaigns, enabling rapid reaction optimization and exploration of chemical space through parallel library synthesis. HTE can be leveraged for multiparameter optimization of reaction conditions for one combination of coupling partners, as illustrated in a report in this issue by Bock and Denmark (DOI: 10.1021/acs.joc.4c00089). Alternatively, HTE can be used for the simultaneous screen of reaction conditions for a diverse range of coupling partners, as discussed by Gesmundo and co-workers at AbbVie (DOI: 10.1021/acs.joc.3c02351) and by Leitch (DOI: 10.1021/acs.joc.3c02311) in partnership with researchers at GSK. The latter screens often reveal a set of reaction conditions that collectively enable access to a broader chemical space than any singular method. While HTE has been leveraged for exploring thermal reactions for over a decade, its adoption for photochemical and electrochemical transformations have only surfaced in recent years. As illustrated in the Perspective by Gesmundo et al. (DOI: 10.1021/acs.joc.3c02351), the widespread adoption of HTE for photochemical transformations required systematic exploration of both equipment and reaction conditions to identify processes that are user-friendly, robust, and lead to high success rates with a broad range of coupling partners. With the advent of HTE equipment for electrochemistry, a similar systematic approach will likely be necessary for the seamless adoption of high-throughput electrochemical transformations across industry and academia. While HTE has enabled the expedited exploration of chemical space, screening remains time and resource intensive. Hence a forward-looking approach entails the use of HTE data to build and apply predictive ML models for synthetic transformations. (32)The earliest paradigms of cross-coupling transformations have inspired over a century of innovations spanning diverse directions. Even as modern chemists continue to advance the more established cross-coupling research themes, these progressively branch into new directions. In parallel, the past few decades have witnessed innovations in technologies such as HTE to accelerate the optimization and discovery of the next generation of cross-couplings across academia and industry, often in partnership. We anticipate that future innovations, including data science and discoveries of new mechanistic manifolds, will continue to expand the diversity of cross-coupling chemistry.Author InformationClick to copy section linkSection link copied!Corresponding AuthorSharon Neufeldt, Department of Chemistry and Biochemistry, Montana State University, Bozeman, Montana 59717, United States, https://orcid.org/0000-0001-7995-3995, Email: [email protected]AuthorsMark R. Biscoe, Department of Chemistry and Biochemistry, The City College of New York (CCNY), New York, New York 10031, United States; The Graduate Center of the City University of New York (CUNY), 365 Fifth Avenue, New York, New York 10016, United States, https://orcid.org/0000-0003-1257-6288Josep Cornella, Max-Planck-Institut für Kohlenforschung, Kaiser-Wilhelm-Platz 1, 45470, Mülheim an der Ruhr, Germany, https://orcid.org/0000-0003-4152-7098Dipannita Kalyani, Discovery Chemistry, Merck & Co., Inc., Rahway, New Jersey 07065, United States, https://orcid.org/0000-0003-4349-8016NotesViews expressed in this editorial are those of the authors and not necessarily the views of the ACS.ReferencesClick to copy section linkSection link copied! This article references 49 other publications. 1(a) Heck, R. F. Arylation, Methylation, and Carboxyalkylation of Olefins by Group VIII Metal Derivatives. J. Am. Chem. Soc. 1968, 90, 5518– 5526, DOI: 10.1021/ja01022a034 Google Scholar1aAcylation, methylation, and carboxyalkylation of olefins by Group VIII metal derivativesHeck, Richard F.Journal of the American Chemical Society (1968), 90 (20), 5518-26CODEN: JACSAT; ISSN:0002-7863. Aryl, methyl, and carboxyalkyl derivatives of Group VIII metal salts, particularly Pd, Rh, and Ru salts, react with olefins to produce aryl-, methyl-, or carboxyalkyl-substituted olefins and reduced metal salt or metal. The reaction may be made catalytic with respect to the metal salt by employing CuCl2 or CuCl2, air, and HCl as reoxidants. The reaction is insensitive to O and water and, therefore, provides an extremely convenient method for the synthesis of a wide variety of olefinic compds. >> More from SciFinder ®https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaF1MXjsVOl&md5=b39805173fa8bbdd1dacd871a6123926(b) Heck, R. F. The Arylation of Allylic Alcohols with Organopalladium Compounds. A New Synthesis of 3-Aryl Aldehydes and Ketones. J. Am. Chem. Soc. 1968, 90, 5526– 5531, DOI: 10.1021/ja01022a035 Google Scholar1bThe arylation of allylic alcohols with organopalladium compounds. A new synthesis of 3-aryl aldehydes and ketonesHeck, Richard F.Journal of the American Chemical Society (1968), 90 (20), 5526-31CODEN: JACSAT; ISSN:0002-7863. Arylpalladium salts, prepd. in situ from arylmercuric salts and a palladium salt, react with primary or secondary allylic alcs. to produce 3-aryl aldehydes or ketones in low to high yields depending upon the mercurial and allylic alc. used. Since the reaction is tolerant of most substituents, it provides a very convenient and useful new method for prepg. a wide variety of 3-aryl aldehydes and ketones. >> More from SciFinder ®https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaF1MXjsVGi&md5=ea2d4e45c3256a975029f256caad1f12(c) Heck, R. F. Allylation of Aromatic Compounds with Organopalladium salts. J. Am. Chem. Soc. 1968, 90, 5531– 5534, DOI: 10.1021/ja01022a036 Google Scholar1cAllylation of aromatic compounds with organopalladium saltsHeck, Richard F.Journal of the American Chemical Society (1968), 90 (20), 5531-4CODEN: JACSAT; ISSN:0002-7863. Arylpalladium salts, prepd. in situ from arylmercuric salts and palladium(II) compds., react with allylic halides at room temp. to produce allylaromatic derivs. Moderate yields were obtained with a wide variety of aromatic compds.; even nitro, ester, and aldehyde groups could be present in the arylmercury compds. >> More from SciFinder ®https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaF1MXjtlOh&md5=3d2ffd908248cce9afda69c4ca269738(d) Heck, R. F. The Palladium-Catalyzed Arylation of Enol Esters, Ethers, and Halides. A New Synthesis of 2-Aryl Aldehydes and Ketones. J. Am. Chem. Soc. 1968, 90, 5535– 5538, DOI: 10.1021/ja01022a037 Google Scholar1dThe palladium-catalyzed arylation of enol esters, ethers, and halides. A new synthesis of 2-aryl aldehydes and ketonesHeck, Richard F.Journal of the American Chemical Society (1968), 90 (20), 5535-8CODEN: JACSAT; ISSN:0002-7863. Arylpalladium salts, generated in situ from arylmercury salts and palladium salts, react with aldehyde enol esters to form arylacetaldehyde derivs., arylacetaldehyde enol ester derivs., arylethylenes, and stilbenes. Vinyl ethers and halides react also, forming stilbenes. Ketone enol esters and arylpalladium salts form α-aryl ketones as the major products. Yields have been generally low but, nonetheless, the reactions provide very simple and convenient methods for obtaining numerous substituted 2-arylaldehydes and ketones. >> More from SciFinder ®https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaF1MXjsVGn&md5=02c16088835e3e2fa3075601b3d9fb09(e) Heck, R. F. Aromatic aloethylation with Palladium and Copper Halides. J. Am. Chem. Soc. 1968, 90, 5538– 5542, DOI: 10.1021/ja01022a038 Google Scholar1eAromatic haloethylation with palladium and copper halidesHeck, Richard F.Journal of the American Chemical Society (1968), 90 (20), 5538-42CODEN: JACSAT; ISSN:0002-7863. Aryl derivs. of Group VIII metal compds., prepd. from Group VIII metal salts and mercury, tin, or lead aryls, react with olefins in the presence of cupric halides to form 2-arylethyl halides. Chlorides are formed in higher yields than bromides. The most generally useful and readily obtainable reactants were arylmercuric halides, with lithium palladium chloride as the Group VIII metal compd. Since only catalytic amts. of the palladium salt are required, this reaction provides a convenient method for introducing 2-haloethyl group into aromatic systems. >> More from SciFinder ®https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaF1MXjtlOj&md5=f5d92733a0d009834d01aabebbecfba6(f) Heck, R. F. The Addition of Alkyl- and Arylpalladium Chlorides to Conjugated Dienes. J. Am. Chem. Soc. 1968, 90, 5542– 5546, DOI: 10.1021/ja01022a039 Google Scholar1fThe addition of alkyl- and arylpalladium chlorides to conjugated dienesHeck, Richard F.Journal of the American Chemical Society (1968), 90 (20), 5542-6CODEN: JACSAT; ISSN:0002-7863. Aryl- and certain alkylpalladium chlorides, prepd. in situ from aryl-or alkylmercury or -tin compds. and lithium palladium chloride, react readily with conjugated dienes to form 1-arylmethyl or 1-alkyl-π-allylpalladium chloride dimers, in low to moderate yields. A catalytic synthesis of arylbutenyl acetates from a conjugated diene, an arylmercuric salt, and lead tetraacetate with a catalytic amt. of palladium acetate is also reported. >> More from SciFinder ®https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaF1MXivFSgtA%253D%253D&md5=513534c0db453e5481b30cd90e0d9729(g) Heck, R. F. A Synthesis of Diaryl Ketones from Arylmercuric Salts. J. Am. Chem. Soc. 1968, 90, 5546– 5548, DOI: 10.1021/ja01022a040 Google Scholar1gA synthesis of diaryl ketones from arylmercuric saltsHeck, Richard F.Journal of the American Chemical Society (1968), 90 (20), 5546-8CODEN: JACSAT; ISSN:0002-7863. Arylmercuric chlorides react with CO and Pd or Rh halide catalysts to form diaryl ketones in fair yields. >> More from SciFinder ®https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaF1MXjslersA%253D%253D&md5=0711a4698230bb289434b32fc9df82532Mizoroki, T.; Mori, K.; Ozaki, A. Arylation of Olefin with Aryl Iodide Catalyzed by Palladium. Bull. Chem. Soc. Jpn. 1971, 44, 581, DOI: 10.1246/bcsj.44.581 Google Scholar2Arylation of olefin with aryl iodide catalyzed by palladiumMizoroki, Tsutomu; Mori, Kunio; Ozaki, AtsumuBulletin of the Chemical Society of Japan (1971), 44 (2), 581CODEN: BCSJA8; ISSN:0009-2673. The arylation of C2H4, CH2:CHMe, CH2:CHCO2Me, and PhCH:CH2 with PhI over PdCl2 or Pd proceeded smoothly in the presence of KOAc (as an HI-acceptor) without polymn. to give the arylated products, styrene, α- and β-methylstyrene, PhCH:CHCO2Me, and trans-stilbene-Ph2C:CH2, resp., in >74% yields. >> More from SciFinder ®https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaE3MXht1Gjsrs%253D&md5=9f31146079d6978e1bb0e6d66bb8b4c63(a) Corriu, R. J. P.; Masse, J. P. Activation of Grignard Reagents by Transition-Metal Complexes. A New and Simple Synthesis of trans-Stilbenes and Polyphenyl. J. Chem. Soc., Chem. Commun. 1972, 144a– 144a, DOI: 10.1039/c3972000144a Google ScholarThere is no corresponding record for this reference.(b) Tamao, K.; Sumitani, K.; Kumada, M. Selective Carbon-Carbon Bond Formation by Cross-Coupling of Grignard Reagents with Organic Halides. Catalysis by Nickel-Phosphine Complexes. J. Am. Chem. Soc. 1972, 94, 4374– 4376, DOI: 10.1021/ja00767a075 Google Scholar3bSelective carbon-carbon bond formation by cross-coupling of Grignard reagents with organic halides. Catalysis by nickel-phosphine complexesTamao, Kohei; Sumitani, Koji; Kumada, MakotoJournal of the American Chemical Society (1972), 94 (12), 4374-6CODEN: JACSAT; ISSN:0002-7863. The reaction of a Grignard reagent with vinyl and aryl halides is catalyzed by a dihalodiphosphinenickel(II) to give cross-coupling products in very high yield. This method can be employed for a variety of Grignard reagents, including those with normal alkyl groups contg. β-hydrogens, and those derived from vinylic and aromatic chlorides. Use of a bidentate diphosphine as a ligand and Et2O as a solvent affords excellent results. m-Dibutylbenzene was obtained in 84% yield by refluxing m-dichlorobenzene and BuMgBr in ether in the presence of a catalytic amt. of [NiCl2(Ph2PCH2CH2PPh2)]. Eleven representative results are given. >> More from SciFinder ®https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaE38Xks1Wgu7g%253D&md5=16baa16277d1c027c493efe58baadecb4Azarian, D.; Dua, S. S.; Eaborn, C.; Walton, D. R. M. Reactions of Organic Halides with R3 MMR3 Compounds (M = Si, Ge, Sn) in the Presence of Tetrakis(triarylphosphine)palladium. J. Organomet. Chem. 1976, 117, C55– C57, DOI: 10.1016/S0022-328X(00)91902-8 Google Scholar4Reactions of organic halides with R3MMR3 compounds (M = silicon, germanium, tin) in the presence of tetrakis(triarylphosphine)palladiumAzarian, Davoud; Dua, Sujan S.; Eaborn, Colin; Walton, David R. M.Journal of Organometallic Chemistry (1976), 117 (3), C55-C57CODEN: JORCAI; ISSN:0022-328X. Reaction of R1X (R1 = Ph, substituted phenyl, PhCH2, substituted benzyl; X = Cl, Br) with R3MMR3 (R = Me, Et, Bu; M = Sn, Ge, Si) in the presence of (R23P)4Pd [R2 = e.g., p-MeOC6H4 (I)] gave 5-98% R3MR1. Thus, reaction of p-NCC6H4CH2Br with Me2SiSiMe3 at 140° 10 hr the in presence of I gave 98% Me3SiCH2C6H4CN-p. Variation of the R2 group in the Pd catalyst has a significant influence on the yield of product. >> More from SciFinder ®https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaE28XlvFarsbo%253D&md5=191b2bcd33bf220ed30326b79a212cd05Baba, S.; Negishi, E. A Novel Stereospecific Alkenyl-Alkenyl Cross-Coupling by a Palladium- or Nickel-Catalyzed Reaction of Alkenylalanes with Alkenyl Halides. J. Am. Chem. Soc. 1976, 98, 6729– 6731, DOI: 10.1021/ja00437a067 Google Scholar5A novel stereospecific alkenyl-alkenyl cross-coupling by a palladium- or nickel-catalyzed reaction of alkenylalanes with alkenyl halidesBaba, Shigeru; Negishi, EiichiJournal of the American Chemical Society (1976), 98 (21), 6729-31CODEN: JACSAT; ISSN:0002-7863. The reaction of (E)-alkenylalanes (I), readily obtainable via hydroalumination of alkynes, with 1-alkenyl halides in the presence of palladium or nickel complexes gave the resp. conjugated (E,E)- and (E,Z)-dienes. >> More from SciFinder ®https://chemport.cas.org/services/resolver?origin=ACS&resolution=optio