Copper-Catalyzed 1,2-Difunctionalization Trifluoromethylamidation of Alkynes Assisted by a Coordinating Group

The radical 1,2-difunctionalization reaction of alkynes has evolved into a versatile approach to multisubstituted alkylenes. However, robust catalytic strategies to perform carboamination are lacking, despite the ubiquity of resulting enamines in natural molecules, bioactive and pharmaceutical compounds. Herein, we show that a bidentate coordinating group judiciously installed on amines could act as an efficient tool for enabling radical trifluoromethylamidation of alkynes. This strategy exhibits a broad substrate scope with good functional group compatibility and is amenable for late-stage functionalization of natural compounds and biologically relevant motifs, allowing a straightforward synthesis of a large library of CF3-containing enamides, the high-value pharmacophores, in a single step from readily accessible amides, Langlois’ reagent, and alkynes. The current methodology can also be successfully extended to difluoromethylamidation of alkynes. Additionally, various mechanistic experiments, such as competition experiments, H/D isotopic exchanging experiments, radical trap experiments, Hammett studies, and kinetic studies, have been performed for a better understanding of the reaction mechanism.