Direct Synthesis of Trifluoromethylated 1,2,4-Triazole-acyl-hydrazones via a One-Pot [3 + 2] Cycloaddition/Substitution Cascade between N-Tosyl-N-aryl Cyanamides and Trifluoromethylated Hydrazonoyl Chlorides.

Herein, an efficient and convenient method for the synthesis of trifluoromethylated 1,2,4-triazole-acyl-hydrazones through a chemoselective [3 + 2] cycloaddition/substitution cascade between trifluoromethylated hydrazonoyl chlorides (TFHCs) and N-tosyl-N-aryl cyanamides (NCTS) is reported. Remarkable features of this reaction include mild conditions, simple operation, and a broad scope, enabling the efficient synthesis of structurally diverse trifluoromethylated 1,2,4-triazole-acyl-hydrazones in good yields. Moreover, the corresponding products could be easily transformed into bis-heterocyclic scaffolds containing triazole and oxadiazole via anion-driven C-F bond activation. Experimental results and DFT calculations converge in supporting the idea that the CF3 group and temperature play a crucial role in the chemoselectivity switch.