Mechanism Switch Between Radical‐Polar Crossover and Radical Buffering

Radical-polar crossover (RPC) is a classic concept that bridges one- and two-electron chemistry. It has been widely used in Cr-catalyzed carbonyl addition reactions to clarify the formation of alkyl chromium(III) intermediate and subsequent carbonyl insertion. Herein, we proposed an orthogonal bonding model, the radical buffering scenario, for Cr-catalyzed carbonyl alkylation. This radical bonding model features the radical dissociation from the alkyl chromium(III) complex followed by the Cr(II)-carbonyl-coupled radical addition to form the C─C bond. The mechanism switch between the radical and polar bonding models is affected by the radical stability, radical nucleophilicity, radical size, and the presence of an α-heteroatom or α-π bond. The collaborative computational and experimental studies have verified the reliability of the radical mechanism. More importantly, we demonstrated that this radical buffering scenario possesses a different stereoselectivity control model from that in the RPC scenario. A general enantioselectivity and diastereoselectivity control model derived from the multiple ligand-radical interactions is thus established for CrCl₂/bisoxazoline-catalyzed asymmetric radical addition.