Copper-Mediated N-Trifluoromethylation of Alkylamines via an In Situ Oxidative Pathway: Controlling the Ambident Electrophilicity of N-Chloramines

The N-trifluoromethylation of aliphatic amines remains a significant synthetic challenge due to the scarcity of effective methods. Here, we report a one-pot two-step method for synthesizing N-trifluoromethylamines from commercially available amines via an unprecedented oxidative pathway. The process relies on the in situ formation of N-chloramines, followed by their reaction with [(phen)CuCF₃] (1) as the trifluoromethylating reagent. Using complex 1 indeed favors the formation of the N–CF3 bond instead of CF3Cl, thereby controlling the ambident electrophilicity of N-chloramines. The reaction occurs at room temperature within 30-90 minutes, yielding the target products in moderate to excellent yields, up to 100 %. Combining DFT calculations and cyclic voltammetry, we demonstrate that the reaction initially proceeds via a single-electron transfer from Cu(I) to the N-chloramine.