RESUMO
A wide range of N-CF3 imidoyl chlorides were synthesized for the first time via the N-trifluoromethylation of nitriles in DCM by using AlCl3-activated PhICF3Cl as the CF3 source. The reactions of them with N-/O-/S-nucleophiles, as well as with 1,3-dipoles, were carried out to efficiently deliver N-CF3 amidines/imidates/thioimidates and N-CF3 azoles, demonstrating that they are a class of scalable NCF3-containing synthons in the synthesis of N-CF3 compounds.
RESUMO
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.
RESUMO
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. PhICF3 Cl 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.
