Enantioselective direct, base-free hydrogenation of ketones by a manganese amido complex of a homochiral, unsymmetrical P–N–P′ ligand

Abstract

The use of manganese in homogeneous hydrogenation catalysis has been a recent focus in the pursuit of more environmentally benign base metal catalysts. It has great promise with its unique reactivity when coupled with metal–ligand cooperation of aminophosphine pincer ligands. Here, a manganese precatalyst Mn(P–N–P′)(CO)₂, where P–N–P′ is the amido form of the ligand (S,S)-PPh₂CHPhCHPhNHCH₂CH₂PⁱPr₂, has been synthesized and used for base-free ketone hydrogenation. This catalyst shows exceptionally high enantioselectivity and good activity, with tolerance for base-sensitive substrates. NMR structural analysis of intermediates formed by the reaction of the amido complex with hydrogen under pressure identified a reactive hydride with an NOE contact with the syn amine proton. Computational analysis of the catalytic cycle reveals that the heterolytic splitting of dihydrogen across the MnN bond in the amido complex has a low barrier while the hydride transfer to the ketone is the turnover-limiting step. The pro-S transition state is found to be usually much lower in energy than the pro-R transition state depending on the ketone structure, consistent with the high (S) enantiomeric excess in the alcohol products. The energy to reach the transition state is higher for the distortion of the in-coming ketone than that of the hydride complex. In a one-to-one comparison with the similar iron catalyst FeH₂(CO)(P–NH–P′), the manganese catalyst is found to have higher enantioselectivity, often over 95% ee, while the iron catalyst has higher activity and productivity. An explanation of these differences is provided on the basis of the more deformable iron hydride complex due to the smaller hydride ligands.