Cu(I)-Catalyzed Enantioselective Epoxidation of Aldehydes with α-Trifluoromethyl Diazosilanes

Abstract

Catalytic epoxidation of readily available aldehydes with diazo compounds is an atom economical strategy to synthesize epoxides. However, the asymmetric epoxidation reaction of aldehydes and fluorinated diazo compounds is challenging, because of the severe racemic background reaction. Herein, we report the first Cu(I)-catalyzed enantioselective epoxidation reaction between aldehydes and α-trifluoromethyl diazosilanes for the synthesis of chiral trifluoromethyl epoxides. This reaction features mild conditions, broad substrate scope, excellent diastereoselectivity and enantioselectivity. The observed positive nonlinear effect supports the ligand acceleration and the achievement of high enantioselectivity with a chiral ligand possessing lower enantiopurity. The gram scale reaction and down-stream transformation based on the removable silyl group demonstrated the synthetic potential of the reaction.