Chemoselective direct reductive trifluoromethylation of amides: a flexible access to functionalized α-trifluoromethylamines

Abstract

The direct transformation of amides is an emerging area in organic synthesis. Starting from common secondary amides, a novel and flexible approach to α-trifluoromethylamines is described. This one-pot method consists of the in situ activation of amides with triflic anhydride (Tf₂O), partial reduction with 1,1,3,3-tetramethyldisiloxane (TMDS), and nucleophilic trifluoromethylation with trifluoromethyltrimethylsilane (TMSCF₃). Thanks to the mild conditions, the reaction exhibited high chemoselectivity and good functional group tolerance.