Deuteriodifluoromethylation and gem-Difluoroalkenylation of Aldehydes Using ClCF2H in Continuous Flow

Publication
Angewandte Chemie 59(33),13885-13890, DOI: 10.1002/anie.202004260

The deuteriodifluoromethyl group (CF2D) represents a challenging functional group due to difficult deuterium incorporation and unavailability of precursor reagents. Herein, we report the use of chlorodifluoromethane (ClCF2H) 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 D2O to provide α-deuteriodifluoromethylated benzyl alcohols or undergo a retro [2+2] cycloaddition under thermal conditions to provide the gem-difluoroalkenylated product."

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