Acid Switchable Reaction of CF₃-Ynones with Hydroxylamine To Form Selectively 3- and 5-CF₃-Isoxazoles

Efficient regioselective one-pot approaches toward 5- and 3-CF₃-isoxazoles were elaborated using reaction of hydroxylamine and its hydrochloride in ethanol. The reaction direction is easily switched by the acidity of the reaction media. In acidic conditions 3-CF₃-isoxazoles are formed while 5-CF₃-isoxazoles can be synthesized in basic media. High (up to 99%) yields, mild conditions, and simplicity of the reaction protocol are the advantages of the proposed methods. The reaction mechanism and regioselectivity were explained by DFT calculations.