Divergent synthesis of unique trifluoromethyl alcohols through Lewis acid-catalyzed anti-Meinwald rearrangement

Abstract

Meinwald rearrangement is a well-established transformation that converts epoxides into aldehydes or ketones via carbocation-mediated rearrangement. In contrast, the anti-Meinwald rearrangement remains challenging due to the inherent preference for carbocation rearrangement and the limited availability of suitable epoxide substrates. Herein, we report the unprecedented synthesis of trifluoromethyl alcohols from in situ generated epoxides via carbocation-mediated elimination or nucleophilic addition pathways, which deviate fundamentally from the conventional Meinwald mechanism.Furthermore, a one-pot synthesis of trifluoromethyl ketones from readily available N-tosylhydrazones and trifluoroacetophenone has also been developed. In addition, a potential pseudo-natural product library was constructed, and the anti-tumor activities of the resulting compounds were evaluated using CCK-8 assays.