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-(<i>R</i>,<i>R</i>)-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 (<i>S</i>)-norfluoxetine, an inhibitor of neural serotonin reuptake and an essential intermediate for pharmaceutical synthesis.