Organocatalytic Asymmetric Construction of Spirooxazines via Chemoselective Cascade Addition of N-Substituted Hydroxylamine with Keto-bis-enone.

Abstract

Spirooxazines represent a privileged heterocyclic scaffold having pronounced biological importance. Herein, we introduce a chiral bifunctional squaramide catalyzed highly chemoselective cascade reaction involving aza-Michael/1,2-addition/oxa-Michael addition of N-substituted hydroxylamine with keto-bis-enones. This strategy enables the synthesis of highly enantioenriched oxa-spirooxazines with a broad substrate tolerance. Scalability and synthetic transformation have demonstrated the feasibility of the protocol. Furthermore, control experiments provided insights into the reaction mechanism.