Acid-Switchable Synthesis of Trifluoromethylated Triazoles and Isoxazoles via Reaction of CF3-Ynones with NaN3: DFT Study of the Reaction Mechanism

A detailed study of the reaction of CF3-ynones with NaN3 was performed. It was found that the reaction permits the selective synthesis of either 4-trifluoroacetyltriazoles or 5-CF3-isoxazoles. The chemoselectivity of the reaction was switchable via acid catalysis. The reaction of CF3-ynones with NaN3 in EtOH produced high yields of 4-trifluoroacetyltriazoles. In contrast, the formation of 5-CF3-isoxazoles was observed under catalysis by acids. This acid-switchable procedure can be performed at sub-gram scale. The possible reaction mechanism was supported by DFT calculations. The synthetic utility of the prepared 4-trifluoroacetyltriazoles was demonstrated.

Automated summary

A detailed study on the reaction of CF3-ynones with NaN3 was conducted, and it was found that the reaction can selectively synthesize different products through acid catalysis. High yields of 4-trifluoroacetyltriazoles were obtained when CF3-ynones reacted with NaN3 in ethanol, while 5-CF3-isoxazoles were formed under acid catalysis. Possible reaction mechanism was supported by DFT calculations, and the synthetic utility of the prepared products was demonstrated.