The activation of aromatic diaryl isoxazoles with strong electron-withdrawing groups,
such as the nitro, triflyl, and the phenylsulfonyl groups, at the 4-position has enabled
the first regio- and diastereoselective difluoromethylation at the 5-position of isoxazoles
by nucleophilic addition using (difluoromethyl) trimethylsilane, Me3SiCF2H, to provide difluoromethylated isoxazolines in good yields. Conjugated styryl-4-nitroisoxazoles
were also nicely converted into the corresponding CF2H adducts with high regio- and excellent diastereoselectivities. Since the trifluoromethylated
analogs of the corresponding diaryl-isoxazolines are effective ectoparasiticides,
represented by fluralaner, should a series of difluoromethylated isoxazolines be obtained,
they would be of great importance as promising drug candidates in this field.