Controllable Regioselective [3+2] Cyclizations of -CF Imidoyl Chlorides and PhPNNC: Divergent Synthesis of -CF Triazoles.

Presented herein are two distinct regiodivergent [3+2] cyclization reactions between -CF imidoyl chlorides and -isocyaniminotriphenylphosphorane (NIITP) that include flexible modulation of the electronic properties of NIITP. The regioselectivity of reactions was different in the absence and presence of the Mo catalyst. The approach provides alternative efficient and scalable routes for -CF triazole synthesis, demonstrating a broad substrate scope, excellent functional group tolerance, and practical advantages.

-CF Imidoyl Chlorides: Scalable -CF Nitrilium Precursors for the Construction of -CF Compounds.

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

Synthesis of -CF Amidines/Imidates/Thioimidates -CF Nitrilium Ions.

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

An N-Trifluoromethylation/Cyclization Strategy for Accessing Diverse N-Trifluoromethyl Azoles from Nitriles and 1,3-Dipoles.

N-Trifluoromethyl azoles are valuable targets in medicinal chemistry, but their synthesis is challenging. Classical preparation of N-CF azoles relies on the functional group interconversions but suffers from tedious N-pre-functionalization and unfriendly agents. Introduction of the CF onto the nitrogen of heterocycles provides a direct route to such motifs, but the N-trifluoromethylation remains underdeveloped.