Deuteriodifluoromethylation and gem-Difluoroalkenylation of Aldehydes Using ClCF2 H in Continuous Flow.

Abstract

The deuteriodifluoromethyl group (CF2 D) represents a challenging functional group due to difficult deuterium incorporation and unavailability of precursor reagents. Herein, we report the use of chlorodifluoromethane (ClCF2 H) gas in the continuous flow deuteriodifluoromethylation and gem-difluoroalkenylation of aldehydes. Mechanistic studies revealed that the difluorinated oxaphosphetane (OPA) intermediate can proceed via alkaline hydrolysis in the presence of D2 O to provide α-deuteriodifluoromethylated benzyl alcohols or undergo a retro [2+2] cycloaddition under thermal conditions to provide the gem-difluoroalkenylated product.