Cycloheptyl-fused-PNN-manganese catalyzed asymmetric transfer hydrogenation of ketones

A family of Mn(I) catalysts containing ferrocene-based chiral PNN tridentate ligands with "aliphatic cyclic" groups is described and tested in the asymmetric transfer hydrogenations of ketones. Various ketones (52 examples), including phenylacetones, phenylpropanones, and heterocyclic substrates could be enantioselectively hydrogenated to the corresponding chiral alcohols with conversions up to 99 % and ee values up to 98 % under mild conditions. A high turnover number of 860 was achieved with a low catalyst loading (S/C = 2000). DFT calculations and control experiments highlighted the significance of remotely polar group (C = O) and cycloheptanyl groups in the catalyst, resulting in enhanced activities and enantiomeric excess (up to 98 % ee), and disclosed the stereocontrol with the assistance of an attractive aromatic pi-pi stacking interaction between the phenyl of a0 and ligand pyridyl rings in the catalytic process. The potential manganese intermediates involved in the catalytic cycle were analyzed. Notably, this catalytic protocol operates under mild conditions, employing low catalyst loading, and shows a potential application in the efficient synthesis of chiral alcohol pharmacophores.