<i>A priori</i> Design of [Mn( <scp>i</scp> )-Cinchona] catalyst for Asymmetric Hydrogenation of Ketones and β-Keto carbonyl Derivatives

Herein, we report an efficient [Mncinchona] chiral catalytic system for the asymmetric hydrogenation of ketones, demonstrating a broad substrate scope and high chemoselectivity. The catalyst selectively reduces ketones, while leaving other reducible functional groups, such as olefins, alkynes, nitriles, nitro groups, and esters, unaffected. The solid-state structure of [Mncinchona] complex revealed that the cinchona ligand acts as bi-dentate ligand, providing valuable insights into its coordination environment and reaction mechanism. DFT calculations suggest that hydrogen molecule activation assisted by water molecules occurs <i>via</i> a six-membered transition state, with enantioselectivity driven by preferential hydride transfer to the <i>si</i> face of the prochiral substrate, resulting in the <i>R</i> configuration. This robust catalytic system shows potential for expansion to the reduction of β-ketoesters and γ-ketoamines and is expected to contribute to further advancements in asymmetric hydrogenation.