Complementary regioselective synthesis of 3,5-disubstituted isoxazoles from ynones

Two regioselective synthetic routes towards 3,5-disubstituted isoxazoles from ynones are reported. One route takes place via first converting the ynones to ynone O-methyl oximes, followed by a palladium-catalyzed intramolecular cyclization. The other involves the formation of 5-hydroxy-4,5-dihydroisoxazoles by a cyclocondensation between ynones and hydroxylamine, and subsequent acid mediated dehydration. The two routes are not only both highly regioselective, but also complementary to each other as a pair of regioisomeric 3,5-disubstituted isoxazoles are readily prepared from one single ynone substrate. The efficiency of the two routes are further evaluated and demonstrated in the synthesis of three representative 3,5-disubstituted isoxazoles. (C) 2018 Elsevier Ltd. All rights reserved.