Mechanisms of nickel-catalyzed reductive cross-coupling reactions

Abstract

Nickel-catalyzed reductive cross-coupling (RCC) reactions using two carbon electrophiles as coupling partners provide one of the most reliable and straightforward protocols for facile construction of valuable C-C bonds in the realm of organic chemistry. In recent years, significant progress has been made in the methodological developments and mechanistic studies of these reactions. This review summarizes four widely accepted mechanisms for RCC reactions that have been proposed by experiments or density functional theory calculations. The major difference between these four types of mechanisms lies in the oxidation state of the active catalyst, the change in the valence of nickel during the catalytic cycle, the involvement of carbon radicals, and the form in which the radicals are present. Herein, we focus on covering representative advancements in experimental and theoretical mechanistic studies, aiming to offer vital mechanistic insights into key intermediates, reaction rates, the activation modes of electrophiles, rate- or selectivity-determining steps, and the origin of the cross-selectivity.

Keywords

Mechanisms / nickel catalysis / reductive cross-coupling / C-C bond formation / carbon radicals

References

[1] Lucas EL.Stereospecific and stereoconvergent cross-couplings between alkyl electrophiles.Nat Rev Chem2017;1:0065

[2] Poremba KE,Reisman SE.Nickel-catalyzed enantioselective reductive cross-coupling reactions.ACS Catal2020;10:8237-46 PMCID:PMC7470226

[3] Wang X,Gong H.Nickel-catalyzed reductive couplings.Top Curr Chem2016;374:43

[4] Liu J,Sessler JL.Cross-electrophile couplings of activated and sterically hindered halides and alcohol derivatives.Acc Chem Res2020;53:1833-45.

[5] Ni S,Mao Y.Ni-catalyzed deaminative cross-electrophile coupling of Katritzky salts with halides via C─N bond activation.Sci Adv2019;5:eaaw9516. PMCID:PMC6598763

[6] Xue W,Wang X,Yin Z.Nickel-catalyzed formation of quaternary carbon centers using tertiary alkyl electrophiles.Chem Soc Rev2021;50:4162-84

[7] Pang X,Shu XZ.Reductive cross-coupling of unreactive electrophiles.Acc Chem Res2022;55:2491-509

[8] Yi L,Chen K,Rueping M.Nickel-catalyzed reductive cross-couplings: new opportunities for carbon-carbon bond formations through photochemistry and electrochemistry.CCS Chem2022;4:9-30.

[9] Durandetti M,Périchon J.Ni-catalyzed activation of α-chloroesters: a simple method for the synthesis of α-arylesters and β-hydroxyesters.Tetrahedron2007;63:1146-53

[10] Ye Y,Xu B.Nickel-catalyzed cross-electrophile allylation of vinyl bromides and the modification of anti-tumour natural medicine β-elemene.Chem Sci2022;13:6959-66 PMCID:PMC9200125

[11] Charboneau DJ,Huang H,Zultanski SL.Homogeneous organic electron donors in nickel-catalyzed reductive transformations.J Org Chem2022;87:7589-609 PMCID:PMC9335070

[12] Charboneau DJ,Barth EL.Tunable and practical homogeneous organic reductants for cross-electrophile coupling.J Am Chem Soc2021;143:21024-36 PMCID:PMC8678384

[13] Zhou J,Xu W,Xu T.Enantioselective C(sp³)-C(sp³) reductive cross-electrophile coupling of unactivated alkyl halides with α-Chloroboronates via dual nickel/photoredox catalysis.J Am Chem Soc2023;145:2081-7.

[14] Zhang P,MacMillan DW.Silyl radical activation of alkyl halides in metallaphotoredox catalysis: a unique pathway for cross-electrophile coupling.J Am Chem Soc2016;138:8084-7 PMCID:PMC5103281

[15] Dongbang S.Ni/photoredox-catalyzed C(sp³)-C(sp³) coupling between aziridines and acetals as alcohol-derived alkyl radical precursors.J Am Chem Soc2022;144:20067-77 PMCID:PMC10281197

[16] Bacauanu V,Yamauchi M.Metallaphotoredox difluoromethylation of aryl bromides.Angew Chem Int Ed Engl2018;57:12543-8.

[17] Yang T,Koh MJ.Photoinduced nickel-catalyzed deaminative cross-electrophile coupling for C(sp²)–C(sp³) and C(sp³)–C(sp³) bond formation.ACS Catal2021;11:6519-25

[18] Liu Y,Mao Y.Electrochemical C-N bond activation for deaminative reductive coupling of Katritzky salts.Nat Commun2021;12:6745 PMCID:PMC8604921

[19] Liu D,Wang ZH.Paired electrolysis-enabled nickel-catalyzed enantioselective reductive cross-coupling between α-chloroesters and aryl bromides.Nat Commun2022;13:7318 PMCID:PMC9705544

[20] Zackasee JLS,Truesdell BL.Synergistic catalyst-mediator pairings for electroreductive cross-electrophile coupling reactions.ACS Catal2022;12:1161-6 PMCID:PMC9635435

[21] Perkins RJ,Hansen EC.Electrochemical Nickel Catalysis for Sp²-Sp³ cross-electrophile coupling reactions of unactivated alkyl halides.Org Lett2017;19:3755-8

[22] Hu X,Cuesta-Galisteo S.Nickel-catalyzed enantioselective electrochemical reductive cross-coupling of aryl aziridines with alkenyl bromides.J Am Chem Soc2023;145:6270-9 PMCID:PMC10037331

[23] Zhang B,Hioki Y.Ni-electrocatalytic Csp³-Csp³ doubly decarboxylative coupling.Nature2022;606:313-8 PMCID:PMC9248350

[24] Nohira I.Nickel-catalyzed cross-electrophile coupling between C(sp²)-F and C(sp²)-Cl bonds by the reaction of ortho-fluoro-aromatic amides with aryl chlorides.ACS Catal2021;11:4644-9

[25] Ni S,Mei H,Pan Y.Ni-catalyzed reductive cross-coupling of amides with aryl iodide electrophiles via C-N bond activation.Org Lett2017;19:2536-9.

[26] Zhu Z,Tong W,Gong H.Ni-catalyzed cross-electrophile coupling of aryl triflates with thiocarbonates via C-O/C-O bond cleavage.Org Lett2021;23:2158-63

[27] Zhao C,Wang X.Ni-catalyzed reductive coupling of alkyl acids with unactivated tertiary alkyl and glycosyl halides.J Am Chem Soc2014;136:17645-51.

[28] Kim S,Gilbert MM.Nickel-catalyzed cross-electrophile coupling of aryl chlorides with primary alkyl chlorides.J Am Chem Soc2020;142:9902-7 PMCID:PMC7418462

[29] Guo P,Jin WJ.Dynamic kinetic cross-electrophile arylation of benzyl alcohols by nickel catalysis.J Am Chem Soc2021;143:513-23.

[30] Zhu Z,Xiao J.Nickel-catalyzed stereo- and enantioselective cross-coupling of gem-difluoroalkenes with carbon electrophiles by C-F bond activation.Angew Chem Int Ed Engl2022;61:e202113209

[31] Chi BK,Gilbert MM,Garcia KJ.In-situ bromination enables formal cross-electrophile coupling of alcohols with aryl and alkenyl halides.ACS Catal2022;12:580-6 PMCID:PMC8979542

[32] Lin T,Qian P,Walsh PJ.Nickel-catalyzed reductive coupling of homoenolates and their higher homologues with unactivated alkyl bromides.Nat Commun2020;11:5638 PMCID:PMC7648641

[33] Kang K.Nickel-catalyzed C(sp³)-C(sp³) cross-electrophile coupling of in situ generated nhp esters with unactivated alkyl bromides.Org Lett2022;24:2853-7. PMCID:PMC9126088

[34] Cui N,Wang YE.Nickel-catalyzed reductive coupling of γ-metalated ketones with unactivated alkyl bromides.Org Lett2022;24:3987-92.

[35] Diccianni JB.Mechanisms of nickel-catalyzed cross-coupling reactions.Trends Chem2019;1:830-44.

[36] Hu X.Nickel-catalyzed cross coupling of non-activated alkyl halides: a mechanistic perspective.Chem Sci2011;2:1867-86

[37] Everson DA.Cross-electrophile coupling: principles of reactivity and selectivity.J Org Chem2014;79:4793-8 PMCID:PMC4049235

[38] Weix DJ.Methods and mechanisms for cross-electrophile coupling of Csp² halides with alkyl electrophiles.Acc Chem Res2015;48:1767-75 PMCID:PMC4484513

[39] Diccianni J,Diao T.Mechanisms of nickel-catalyzed coupling reactions and applications in alkene functionalization.Acc Chem Res2020;53:906-19. PMCID:PMC7958188

[40] Yang T,Luo Y,Lan Y.Chemoselective union of olefins, organohalides, and redox-active esters enables regioselective alkene dialkylation.J Am Chem Soc2020;142:21410-9

[41] Duan A,Lan Y.Mechanistic views and computational studies on transition-metal-catalyzed reductive coupling reactions.Chem Soc Rev2022;51:9986-10015

[42] Wang Y.DFT study of the mechanisms of transition-metal-catalyzed reductive coupling reactions.Curr Org Chem2020;24:1367-83.

[43] Gu J,Xue W.Nickel-catalyzed reductive coupling of alkyl halides with other electrophiles: concept and mechanistic considerations.Org Chem Front2015;2:1411-21

[44] Zhang SQ.Mechanism and selectivity control in Ni- and Pd-catalyzed cross-couplings involving carbon-oxygen bond activation.Acc Chem Res2021;54:2158-71.

[45] Gutierrez O,Primer DN,Kozlowski MC.Nickel-catalyzed cross-coupling of photoredox-generated radicals: uncovering a general manifold for stereoconvergence in nickel-catalyzed cross-couplings.J Am Chem Soc2015;137:4896-9. PMCID:PMC4576934

[46] Kolahdouzan K,Grandner JM,Terrett JA.Dual photoredox/nickel-catalyzed conversion of aryl halides to aryl aminooxetanes: computational evidence for a substrate-dependent switch in mechanism.ACS Catal2020;10:405-11

[47] Xu J,Zhao X,Zhang D.DFT mechanistic study of Ir^III/Ni^II-metallaphotoredox-catalyzed difluoromethylation of aryl bromides.Inorg Chem2021;60:8682-91

[48] Biswas S.Mechanism and selectivity in nickel-catalyzed cross-electrophile coupling of aryl halides with alkyl halides.J Am Chem Soc2013;135:16192-7. PMCID:PMC3946589

[49] Everson DA,Weix DJ.Nickel-catalyzed reductive cross-coupling of aryl halides with alkyl halides.J Am Chem Soc2010;132:920-1

[50] Everson DA,Weix DJ.Replacing conventional carbon nucleophiles with electrophiles: nickel-catalyzed reductive alkylation of aryl bromides and chlorides.J Am Chem Soc2012;134:6146-59 PMCID:PMC3324882

[51] Wotal AC,Weix DJ.Stoichiometric reactions of acylnickel^II complexes with electrophiles and the catalytic synthesis of ketones.Organometallics2014;33:5874-81 PMCID:PMC4210159

[52] Sheng J,Zhang HR,Wang YN.Nickel-catalyzed reductive cross-coupling of aryl halides with monofluoroalkyl halides for late-stage monofluoroalkylation.Angew Chem Int Ed Engl2018;57:7634-9

[53] Brauer DJ.Bonding of aromatic hydrocarbons to nickel (0). Structure of bis (tricyclohexylphosphine)(1,2-.eta.2-anthracene) nickel (0)-toluene.Inorg Chem1977;16:884-91

[54] Ren Q,Gong H.DFT study of the single electron transfer mechanisms in Ni-Catalyzed reductive cross-coupling of aryl bromide and alkyl bromide.J Organomet Chem2014;770:130-5

[55] Kumar GS,Brzozowska A,Zhu C.Nickel-catalyzed chain-walking cross-electrophile coupling of alkyl and aryl halides and olefin hydroarylation enabled by electrochemical reduction.Angew Chem Int Ed Engl2020;59:6513-9

[56] Wang X,Peng Y.Ni-catalyzed reductive coupling of electron-rich aryl iodides with tertiary alkyl halides.J Am Chem Soc2018;140:14490-7.

[57] Ji H,Tai L.Nickel-catalyzed enantioselective coupling of acid chlorides with α-bromobenzoates: an asymmetric acyloin synthesis.J Am Chem Soc2022;144:23019-29

[58] Guan H,Walsh PJ.Nickel/photoredox-catalyzed asymmetric reductive cross-coupling of racemic α-chloro esters with aryl iodides.Angew Chem Int Ed Engl2020;59:5172-7

[59] Lau SH,Steiman TJ,Parasram M.Ni/photoredox-catalyzed enantioselective cross-electrophile coupling of styrene oxides with aryl iodides.J Am Chem Soc2021;143:15873-81 PMCID:PMC8667461

[60] Wang H,Wu X,Xu T.Modular and facile access to chiral α-aryl phosphates via dual nickel- and photoredox-catalyzed reductive cross-coupling.J Am Chem Soc2022;144:3989-97

[61] Yuan M,Badir SO,Gutierrez O.On the nature of C(sp³)- C(sp²) bond formation in nickel-catalyzed tertiary radical cross-couplings: a case study of Ni/photoredox catalytic cross-coupling of alkyl radicals and aryl halides.J Am Chem Soc2020;142:7225-34 PMCID:PMC7909746

[62] Paul A,Vannucci AK.Photoredox-assisted reductive cross-coupling: mechanistic insight into catalytic aryl-alkyl cross-couplings.J Org Chem2017;82:1996-2003

[63] Hamby TB,Sevov CS.Controlling Ni redox states by dynamic ligand exchange for electroreductive Csp³-Csp² coupling.Science2022;376:410-6. PMCID:PMC9260526

[64] Li Z,Wang X,Zhang Y.Electrochemically enabled, nickel-catalyzed dehydroxylative cross-coupling of alcohols with aryl halides.J Am Chem Soc2021;143:3536-43

[65] Diccianni JB,Hu C.Mechanistic characterization of (Xantphos)Ni(I)-mediated alkyl bromide activation: oxidative addition, electron transfer, or halogen-atom abstraction.J Am Chem Soc2019;141:1788-96.

[66] Funes-Ardoiz I,Maseras F.halide abstraction competes with oxidative addition in the reactions of aryl halides with [Ni(PMe_n Ph_(3-n))₄].Chemistry2017;23:16728-33 PMCID:PMC5725734

[67] Kehoe R,Manzoor A.Reactions of the Ni(0) Compound Ni(PPh ₃)₄ with unactivated alkyl halides: oxidative addition reactions involving radical processes and nickel(I) intermediates.Organometallics2018;37:2450-67.

[68] Yoo C,Jung Y.Mechanistic study on C-C bond formation of a nickel(I) monocarbonyl species with alkyl iodides: experimental and computational investigations.Organometallics2015;34:4305-11

[69] Lin Q,Liu P.Monovalent nickel-mediated radical formation: a concerted halogen-atom dissociation pathway determined by electroanalytical studies.J Am Chem Soc2021;143:14196-206 PMCID:PMC8820414

[70] Guo L,Zhang Y.General method for enantioselective three-component carboarylation of alkenes enabled by visible-light dual photoredox/nickel catalysis.J Am Chem Soc2020;142:20390-9

[71] Jiang F.Theoretical investigation of the mechanisms of the biphenyl formation in Ni-catalyzed reductive cross-coupling system.J Organomet Chem2014;757:72-8

[72] Liu J,Zhang X.Preparation of vinyl arenes by nickel-catalyzed reductive coupling of aryl halides with vinyl bromides.Angew Chem Int Ed Engl2016;55:15544-8

[73] Long C,Su M,Tan W.Highly chemoselective access to 2,2′-diaminobiaryls via Ni-catalyzed protecting-group-free coupling of 2-haloanilines.ACS Catal2020;10:13641-9

[74] Long CY,Ma C.Highly chemoselective Ni-catalyzed protecting-group-free 2,2'-biphenol synthesis and mechanistic insights.Org Lett2022;24:4155-9.

[75] Yue H,Shen L.Nickel-catalyzed C-N bond activation: activated primary amines as alkylating reagents in reductive cross-coupling.Chem Sci2019;10:4430-5. PMCID:PMC6482441

[76] Lin Q.Mechanism of Ni-catalyzed reductive 1,2-dicarbofunctionalization of alkenes.J Am Chem Soc2019;141:17937-48 PMCID:PMC7058187

[77] Cornella J,Martin R.Combined experimental and theoretical study on the reductive cleavage of inert C-O bonds with silanes: ruling out a classical Ni(0)/Ni(II) catalytic couple and evidence for Ni(I) intermediates.J Am Chem Soc2013;135:1997-2009

[78] Chen H,Zhu C.Reactivity in nickel-catalyzed multi-component sequential reductive cross-coupling reactions.Angew Chem Int Ed Engl2022;61:e202204144

[79] Wang X,Ye J,Cheng R.Theoretical investigation of mechanism on nickel-catalyzed electrochemical cross-coupling of aryl bromides and arylamines.Catal Sci Technol2023;13:1032-40

[80] Tang T,Wild T,Minteer SD.Investigating oxidative addition mechanisms of allylic electrophiles with low-valent Ni/Co catalysts using electroanalytical and data science techniques.J Am Chem Soc2022;144:20056-66.

[81] Ting SI,Doyle AG.Oxidative addition of aryl halides to a Ni(I)-bipyridine complex.J Am Chem Soc2022;144:5575-82

[82] Till NA,MacMillan DWC.The application of pulse radiolysis to the study of Ni(I) intermediates in ni-catalyzed cross-coupling reactions.J Am Chem Soc2021;143:9332-7

[83] Breitenfeld J,Hu X.Bimetallic oxidative addition in nickel-catalyzed alkyl-aryl kumada coupling reactions.Organometallics2014;33:5708-15.

[84] Breitenfeld J,Wodrich MD.Bimetallic oxidative addition involving radical intermediates in nickel-catalyzed alkyl-alkyl kumada coupling reactions.J Am Chem Soc2013;135:12004-12

[85] Laskowski CA,Baldwin SM,Iluc VM.Synthesis and reactivity of two-coordinate Ni(I) alkyl and aryl complexes.J Am Chem Soc2013;135:18272-5

[86] Ju L,LiBretto NJ.Reactivity of (bi-Oxazoline)organonickel complexes and revision of a catalytic mechanism.J Am Chem Soc2021;143:14458-63. PMCID:PMC8883516

[87] Thane TA.Ligand-based control of nickel catalysts: switching chemoselectivity from one-electron to two-electron pathways in competing reactions of 4-halotetrahydropyrans.Org Lett2022;24:5003-8

[88] Shu W,Quirós MT,Cárdenas DJ.Ni-catalyzed reductive dicarbofunctionalization of nonactivated alkenes: scope and mechanistic insights.J Am Chem Soc2019;141:13812-21

[89] Zhu C,Chen H,Rueping M.Reductive cross-coupling of α-oxy halides enabled by thermal catalysis, photocatalysis, electrocatalysis, or mechanochemistry.Angew Chem Int Ed Engl2022;61:e202204212

[90] Day CS,Ton SJ,Gutierrez O.Elucidating electron-transfer events in polypyridine nickel complexes for reductive coupling reactions.Nat Catal2023;6:244-53

[91] Tang T,Min DS.Interrogating the mechanistic features of Ni(I)-mediated aryl iodide oxidative addition using electroanalytical and statistical modeling techniques.J Am Chem Soc2023;145:8689-99

[92] Chen PP,Greene MA.A unified explanation for chemoselectivity and stereospecificity of Ni-catalyzed kumada and cross-electrophile coupling reactions of benzylic ethers: a combined computational and experimental study.J Am Chem Soc2019;141:5835-55

[93] Hewitt KA,Thane TA.Nickel-catalyzed domino cross-electrophile coupling dicarbofunctionalization reaction to afford vinylcyclopropanes.ACS Catal2021;11:14369-80

[94] Lucas EL,Chen PP,Hong X.Engaging sulfonamides: intramolecular cross-electrophile coupling reaction of sulfonamides with alkyl chlorides.J Org Chem2020;85:1775-93

[95] Xu Z,Jiang J.Theoretical investigation on Ni-catalyzed C(sp³)-F activation and ring contraction of tetrahydropyrans: exploration of an S_N2 pathway.Organometallics2018;37:1114-22

[96] Lucas EL,Castro AJ.Nickel-catalyzed cross-electrophile coupling of the difluoromethyl group for fluorinated cyclopropane synthesis.Synlett2021;32:1525-30

[97] Sanford AB,McGinnis TM,Hong X.Nickel-catalyzed alkyl-alkyl cross-electrophile coupling reaction of 1,3-dimesylates for the synthesis of alkylcyclopropanes.J Am Chem Soc2020;142:5017-23 PMCID:PMC7864534