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Deuteriodifluoromethylation and gem ‐Difluoroalkenylation of Aldehydes Using ClCF 2 H in Continuous Flow
Author(s) -
Fu Wai Chung,
Jamison Timothy F.
Publication year - 2020
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.202004260
Subject(s) - cycloaddition , chemistry , reagent , unavailability , continuous flow , hydrolysis , deuterium , flow chemistry , functional group , nitrile , organic chemistry , medicinal chemistry , combinatorial chemistry , catalysis , polymer , physics , quantum mechanics , mechanics , engineering , reliability engineering
The deuteriodifluoromethyl group (CF 2 D) represents a challenging functional group due to difficult deuterium incorporation and unavailability of precursor reagents. Herein, we report the use of chlorodifluoromethane (ClCF 2 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 D 2 O to provide α‐deuteriodifluoromethylated benzyl alcohols or undergo a retro [2+2] cycloaddition under thermal conditions to provide the gem ‐difluoroalkenylated product.