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Cross-Electrophile Coupling to Form Sterically Hindered C(sp<sup>2</sup>)–C(sp<sup>3</sup>) Bonds: Ni and Co Afford Complementary Reactivity

Tung-Kung Wu, Anthony J. Castro, Kasturi Ganguli, Madeline E. Rotella, Ning Ye, Fabrice Gallou, Bin Wu, Daniel J. Weix

2025Journal of the American Chemical Society14 citationsDOIOpen Access PDF

Abstract

The formation of sterically hindered C(sp 2 )–C(sp 3 ) bonds could be a useful synthetic tool but has been understudied in cross-electrophile coupling. Here, we report two methods that couple secondary alkyl bromides with aryl halides that contain sterically hindered C–X bonds: 1) ortho -substituted aryl bromides with nickel catalysts and 2) di- ortho -substituted aryl iodides with cobalt catalysts. Stoichiometric experiments and deuterium labeling studies show that 1) [Co] is better than [Ni] for oxidative addition of di- ortho -substituted Ar–I and 2) [Co] is better than [Ni] for radical capture/reductive elimination steps with di- ortho -substituted arenes. For both metals, Ar–H side products observed in reactions with low-yielding di- ortho -substituted aryl iodides appear to arise from Ar• formation and hydrogen-atom transfer from the solvent. While the origins of the differences in scope are not yet understood, these studies demonstrate a previously unknown complementarity between nickel and cobalt in cross-electrophile coupling.

Topics & Concepts

ChemistrySteric effectsElectrophileReactivity (psychology)Coupling (piping)Carbon-13StereochemistryComputational chemistryCrystallographyOrganic chemistryNuclear physicsCatalysisPhysicsAlternative medicineMedicineMechanical engineeringEngineeringPathologyCatalytic Cross-Coupling ReactionsCatalytic C–H Functionalization MethodsAsymmetric Hydrogenation and Catalysis