Cobalt‐Catalyzed Asymmetric Hydrogenation of α‐Hydroxy Ketones Enabled by a Carboxylic Acid Additive Promotion Strategy

Highly enantioselective hydrogenation of α‐hydroxy ketones was achieved by applying the catalytic combination of cobalt acetate and chiral Ph‐BPE ligand, supplemented by a carboxylic acid additive promotion strategy. The carboxylic acid additive significantly increases both reactivity and enantioselectivity, allowing for the highly efficient generation of chiral 1,2‐diols with up to 99% ee. The application utility is proved through derivations and a total synthesis of (R)‐(‐)‐Eliprodil. Mechanistic studies including control experiments and DFT calculations support the proposed catalytic mechanism and explain the origin of enantioselectivity.