Deuteriodifluoromethylation and gem-Difluoroalkenylation of Aldehydes Using ClCF2 H in Continuous Flow
Wai Chung Fu1, Timothy F Jamison1
1Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA, 02139, USA.
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.
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