Enantioselective Iridium-Catalyzed Hydrogenation of alpha-Keto Amides to alpha-Hydroxy Amides

A highly enantioselective iridium-catalyzed hydrogenation of alpha-keto amides to form alpha-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-(2amino-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.