Construction of chiral N,O-hemiaminals via a copper-catalyzed enantioselective Michael/N-hemiacetalization cascade reaction

Abstract

An efficient Michael/N-hemiacetalization cascade reaction of 5-aminoisoxazoles with β,γ-unsaturated α-ketoesters was developed under the catalysis of a chiral copper complex. A series of optically pure six-membered ring N,O-hemiaminals were obtained with excellent yields (up to 96% yield) and high enantioselectivities (up to 98% ee). The possible transition state was supported by DFT calculations and thereby the corresponding mechanism was proposed.