Sterically Diversified C(sp ³ )–C(sp ³ ) Coupling between Ketone and Carboxylic Acid-Derived Radical Precursors via Ni/Photoredox Catalysis

We report a synergistic photoredox and nickel-catalyzed strategy for sterically diversified fragment coupling between preactivated ketones and carboxylic acids. By employing prearomatic intermediates and redox-active esters, distinct alkyl radicals generated via a photoredox-neutral process undergo nickel-catalyzed S H 2 homolytic substitution to achieve heteroselective radical–radical coupling. This synthetic platform features optimal steric diversification, as both ketones and acids can orthogonally serve as primary, secondary, and tertiary radical precursors, enabling facile access to construct diverse C(sp 3 )–C(sp 3 ) linkages, including the particularly challenging all-carbon quaternary centers.