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.
Muzalevskiy et al. (Thu,) studied this question.