Enantioselective and Diastereoselective Ir-Catalyzed Hydrogenation of α-Substituted ß-Ketoesters via Dynamic Kinetic Resolution.

An iridium/f-amphol catalytic system for the enantioselective hydrogenation of α-substituted ß-ketoesters via dynamic kinetic resolution is reported. The desired anti products were obtained in high yields (up to 98%) with good diastereoselectivity (up to 96:4 diastereometic ratio (dr)) and excellent enantioselectivity (up to >99% enantiomeric excess (ee)). A catalytic model is proposed to explain the stereoselectivity.

Enantioselective Iridium-Catalyzed Hydrogenation of α-Keto Amides to α-Hydroxy Amides.

A highly enantioselective iridium-catalyzed hydrogenation of α-keto amides to form α-hydroxy amides has been achieved with excellent results (up to >99% conversion and up to >99% ee, TON up to 100 000). As an example, this protocol was applied to the synthesis of (S)-4-(2-amino-1-hydroxyethyl)benzene-1,2-diol, the enantiomer of norepinephrine, which is widely used as an injectable drug for the treatment of critically low blood pressure. Density functional theory (DFT) calculations were also carried out to reveal the reaction mechanism.