Visible-light-mediated catalyst-free synthesis of trifluoromethyl(spiro)-epoxides bearing contiguous quaternary centers

Abstract

Epoxides are regarded as important pharmacophores that can have a huge effect on improving drug activity. However, epoxides with continuous quaternary centers are challenging to construct due to steric hindrance. Herein, we report a visible-light-induced cycloaddition reaction of N-tosylhydrazones with trifluoromethyl ketones to synthesize trifluoromethyl(spiro)-epoxides bearing contiguous quaternary centers under metal-free and catalyst-free conditions. This strategy could be adapted to a variety of groups and a wide range of applications, including the modification of drug derivatives and gram-scale synthesis. Furthermore, the obtained epoxides could be efficiently converted into other valuable building blocks, such as trifluoroacetone analogues.