Stereodivergent Synthesis of Epoxides and Oxazolidinones via the Halohydrin Dehalogenase-Catalyzed Desymmetrization Strategy

Abstract

Catalytic stereoselective desymmetrization of prochiral compounds to valuable chiral molecules is of interest in asymmetric synthesis. Here, we report the development of an efficient biocatalytic desymmetrization strategy for the stereodivergent synthesis of various chiral epoxides and oxazolidinones by the identification and engineering of halohydrin dehalogenases. The use of stereocomplementary halohydrin dehalogenases for the desymmetrization of 2-substituted-1,3-dichloro-2-propanols generates chiral epoxides in up to 95% yield and 99% ee by a single-step dehalogenation reaction, as well as chiral oxazolidinones in up to 88% yield and >99% ee via a dehalogenation and cyanate-mediated epoxide ring-opening cascade reaction. We also propose a probable mechanism for stereoselectivity control in the halohydrin dehalogenase-catalyzed desymmetrization reaction.