Nickel-Catalyzed Asymmetric Reductive Couplings of Ketones for the Synthesis of Enantioenriched Tertiary Alcohols

Nickel-catalyzed asymmetric reductive coupling has emerged as a direct strategy for converting ketones into enantioenriched tertiary alcohols without the prior preparation of organometallic nucleophiles. In this review, we summarize recent advances in reductive arylation and alkenylation with aryl and alkenyl halides, intermolecular and cascade couplings involving alkenes and alkynes, reductive annulations, and intramolecular reductive cyclizations. The discussion focuses on reactions conducted under chemically or electrochemically reducing conditions in which the ketone carbonyl carbon becomes a stereogenic tertiary alcohol center, including transformations that initially afford protected alcohols or lactones. Particular emphasis is placed on reaction design, catalyst and ligand selection, reductant effects, substrate scope, and mechanistic differences among organonickel addition to ketones, oxidative cyclization, and Ni-H mediated hydrometallation. The current limitations and remaining opportunities for expanding the substrate scope and developing general intermolecular reactions are also discussed.