Chromium Catalyzed Asymmetric Reformatsky Reaction

Abstract This study describes an unprecedented chromium‐catalyzed asymmetric Reformatsky reaction, enabling the synthesis of chiral β ‐hydroxy carbonyl compounds from α ‐chlorinated or α ‐brominated esters and amides. By employing a chiral chromium/diarylamine bis(oxazoline) catalyst, we achieved relatively broad functional group tolerance. Distinct from known reports, the protocol operates under both classical and photoredox conditions, facilitated by the in situ formation of a nucleophilic chiral chromium intermediate through a radical‐polar crossover mechanism. Preliminary mechanistic insights, supported by DFT calculations, identify the nucleophilic aldehyde addition as the key stereo‐determining step. This approach not only overcomes the limitations of existing Reformatsky reactions but also provides a versatile strategy for accessing complex chiral molecules.