摘要：Tianrui Wu,∇Anthony J. Castro,∇Kasturi Ganguli, Madeline E. Rotella,*Ning Ye, Fabrice Gallou, Bin Wu,*and Daniel J. Weix*

转自：康龙化成

Cross-Electrophile Coupling to FormSterically Hindered C(sp2)−C(sp3) Bonds Niand Co AffordComplementary Reactivity

Tianrui Wu,∇Anthony J. Castro,∇ Kasturi Ganguli, Madeline E. Rotella,*Ning Ye, Fabrice Gallou, Bin Wu,* and Daniel J. Weix*

Department of Chemistry, Roy and Diana VagelosLaboratories, University of Pennsylvania, Philadelphia, Pennsylvania 19104,United States

Chemical & Analytical Development,Suzhou Novartis Technical Development Company Limited, Changshu, Jiangsu215537, China;

Department of Chemistry, UW-Madison,Madison, Wisconsin 53706, United States;

Chemical & Analytical Development,Novartis Pharma AG, Basel 4056, Switzerland;

—J. Am. Chem. Soc., 2025 ,https://doi.org/10.1021/jacs.4c16912

Recommended by Murong Xu_MC3

KEYWORDS: Cross-ElectrophileCoupling, XEC,NiCatalysis, Co Catalysis (反应类型), C(sp2)-C(sp3) (成键类型), secondary alkyl bromides, aryl halides (原料),aryl alkane (产物),Sterically Hindered (其他)

ABSTRACT:Theformation of sterically hindered C(sp2)-C(sp3) bonds could be a useful synthetic toolbut has been understudied in cross-electrophile coupling. Here, we report twomethods that couple secondary alkyl bromides with aryl halides thatcontain sterically hindered C−X bonds: 1) ortho-substituted aryl bromides with nickelcatalysts and 2) di-ortho-substitutedaryl iodides with cobalt catalysts. Stoichiometric experiments and deuteriumlabeling studies show that 1) [Co] is better than [Ni] for oxidative additionof di-ortho-substituted Ar−Iand 2) [Co] is better than [Ni] for radical capture/reductive elimination stepswith di-ortho-substituted arenes. Forboth metals, Ar−Hside products observed in reactions with low-yielding di-ortho-substitutedaryl iodides appear to arise from Ar• formation and hydrogen-atom transferfrom the solvent. While the origins of the differences in scope are not yetunderstood, these studies demonstrate a previously unknown complementaritybetween nickel and cobalt in cross-electrophile coupling.

Substrate Scope and Limitations forHindered Cross-Electrophile Coupling

Proposed Mechanism

Prof.Madeline E. Rotella, Bin Wu and Daniel J. Weix et al haveestablished the current state of the art for hindered C(sp2)−C(sp3)bond formation in both Ni and Co XEC. The cobalt conditions are shown tocomplement the Ni conditions well, allowing the coupling of 2,6-dimethylaryliodides with secondary alkyl bromides under XEC conditions for the first time.Nickel catalysts fail with these more challenging substrates in both theoxidative addition step and the radical capture/reductive elimination step.Cobalt catalysts appear better suited to these steps but begin to fail withgroups larger than methyl. In both cases, Ar−H formation from an Ar•intermediate (likely formed during the oxidative addition step) is the majorside reaction. These conditions should be immediately useful for synthesis, andthe finding that cobalt allows for more hindered coupling reactions shoulddrive further studies in Co XEC.

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