Acid Switchable Reaction of CF 3 -Ynones with Hydroxylamine To Form Selectively 3- and 5-CF 3 -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.