Acid-Switchable Synthesis of Trifluoromethylated Triazoles and Isoxazoles via Reaction of CF(3)-Ynones with NaN(3): DFT Study of the Reaction Mechanism

A detailed study of the reaction of CF(3)-ynones with NaN(3) was performed. It was found that the reaction permits the selective synthesis of either 4-trifluoroacetyltriazoles or 5-CF(3)-isoxazoles. The chemoselectivity of the reaction was switchable via acid catalysis. The reaction of CF(3)-ynones with NaN(3) in EtOH produced high yields of 4-trifluoroacetyltriazoles. In contrast, the formation of 5-CF(3)-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.