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 π–π stacking interaction between the
catalyst and the substrate plays an important role.