Study on the Influence of Electron-Withdrawing α- and β-Substituents on the Kinetic Resolution of cis-Vinyl Epoxide via Chiral Lewis Base-Catalyzed Ring Opening

Abstract

Vinyl epoxide has a carbon-carbon double bond adjacent to an epoxide. It provides not only the intrinsic properties of both functional groups but also reactivities that cannot be accessed from each moiety. Therefore, vinyl epoxide serves as a versatile precursor to various functional groups in organic synthesis. Consequently, various methods and strategies of vinyl epoxide synthesis have been developed. However, it is still difficult to synthesize enantioenriched vinyl epoxide. Kinetic resolution can be a practical alternative when there is no available enantioselective synthetic method. In the previous work, kinetic resolution of vinyl epoxide with (R,R)-Denmark’s catalyst was successfully developed for the preparation of enantioenriched α,β-dichloro-cis-vinyl epoxide intermediates in the total synthesis of chlorosulfolipids. In this research, cis-vinyl epoxides containing an electron withdrawing α-substituent as well as β-chloro-cis-vinyl epoxide were examined in order to investigate the effect of α- and β-chlorine substituents. Unfortunately, kinetic resolution of cis-vinyl epoxides containing an electron withdrawing α-substituent was considerably less effective than kinetic resolution of α,β-dichloro-cis-vinyl epoxides. Previously, the selectivity was dependent on the configuration of the β-chlorine substituent in the kinetic resolution of α,β-dichloro-cis-vinyl epoxides. Therefore, kinetic resolution of β-chloro-cis-vinyl epoxides was carried out to examine the effects of the β-chlorine substituent on the selectivity of the kinetic resolution of cis-vinyl epoxide. Although kinetic resolution of 1,3-anti-β-chloro-cis-vinyl epoxide proceeded with poor selectivity, kinetic resolution of a diastereomeric 1,3-syn-β-chloro-cis-vinyl epoxide is expected to be more efficient on the basis of the previous studies on α,β-dichloro-cis-vinyl epoxides.