Nickel-Catalyzed Asymmetric Hydrogenation ofγ-Keto Acids, Esters, and Amides to Chiralγ-Lactones andγ-Hydroxy Acid Derivatives

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

Automated summary

A highly efficient asymmetric hydrogenation method has been developed for the synthesis of chiral gamma-hydroxy acid derivatives. The method shows excellent enantioselectivity and has the potential to be applied in the synthesis of chiral compounds and key intermediates for pharmaceutical synthesis.