Amino Acid Derived Chiral Aminobenzimidazole Manganese Catalysts for Asymmetric Transfer Hydrogenation of Ketones

A series of Mn(I) catalysts with chiral bidentate benzimidazoles derived from easily available amino acids has been developed. These types of phosphine-free chiral Mn catalysts demonstrate high activity and enantioselectivity in asymmetric transfer hydrogenation (ATH) for a broad range of ketone substrates. A bulkier substrate, such as 2,6-dichloro-3-fluoroacetophenone, can be converted into the drug intermediate alcohol with up to 90% yield and 92% ee (e.g., crizotinib). On the basis of experimental and DFT studies, a possible mechanism for this Mn-catalyzed ATH is also proposed. DFT calculations further render a plausible model for enantiocontrol in ketone hydrogenation, in which the pi-pi stacking interaction between the catalyst and the substrate plays an important role.