An efficient methodology for the synthesis of a wide range of N-CF3 imidic acid derivatives is presented. In this reaction, N-CF3 nitrilium ions were generated via N-trifluoromethylation of nitriles using PhICF3Cl under catalysis with DMAP, followed by the capture of N-, O-, or S-centered nucleophiles to give diverse N-CF3 amidines, imidates, and thioimidates. The method provides a platform for preparing N-CF3 compounds with potential applications.

N‐Trifluoromethyl azoles are valuable targets in medicinal chemistry, but their synthesis is challenging. Classical preparation of N‐CF3 azoles relies on the functional group interconversions but suffers from tedious N‐pre‐functionalization and unfriendly agents. Introduction of the CF3 onto the nitrogen of heterocycles provides a direct route to such motifs, but the N‐trifluoromethylation remains underdeveloped. Reported here is an alternative and scalable cyclization strategy based on NCF3‐containing synthons for constructing N‐CF3 azoles. The approach involves the N‐trifluoromethylation of nitriles followed by a [3+2] cyclization between resulting N‐CF3 nitrilium derivatives and 1,3‐dipoles. PhICF3Cl was an effective CF3 source for the transformation. As a result, a generic platform is established to divergently synthesize N‐trifluoromethylated tetrazoles, imidazoles, and 1,2,3‐triazoles by using sodium azide, activated methylene isocyanides, and diazo compounds as dipoles.

N-Trifluoromethyl azoles are valuable targets in medicinal chemistry,b ut their synthesis is challenging.C lassical preparation of N-CF 3 azoles relies on the functional group interconversions but suffers from tedious N-pre-functionalization and unfriendly agents.I ntroduction of the CF 3 onto the nitrogen of heterocycles provides adirect route to such motifs, but the N-trifluoromethylation remains underdeveloped. Reported here is an alternative and scalable cyclization strategy based on NCF 3 -containing synthons for constructing N-CF 3 azoles.T he approach involves the N-trifluoromethylationo f nitriles followed by a[ 3 + +2] cyclization between resulting N-CF 3 nitrilium derivatives and 1,3-dipoles.P hICF 3 Cl was an effective CF 3 source for the transformation. As ar esult, ag eneric platform is established to divergently synthesizeNtrifluoromethylated tetrazoles,i midazoles,a nd 1,2,3-triazoles by using sodium azide,a ctivated methylene isocyanides,a nd diazoc ompounds as dipoles.