Nickel-Catalyzed Asymmetric Hydrogenation of γ-Keto Acids, Esters, and Amides to Chiral γ-Lactones and γ-Hydroxy Acid Derivatives.

Abstract

A highly efficient asymmetric hydrogenation of a series of γ-keto acid derivatives, including γ-keto acids, esters, and amides, using a Ni-(R,R)-QuinoxP* complex as the catalyst has been developed to afford chiral γ-hydroxy acid derivatives with excellent enantioselectivities, up to 99.9% ee. This method provides not only an economical one-pot approach for the synthesis of chiral γ-lactones but also access to (S)-norfluoxetine, an inhibitor of neural serotonin reuptake and an essential intermediate for pharmaceutical synthesis.