Synthesis of Trisubstituted Isoxazoles by Palladium(II)-Catalyzed Cascade Cyclization–Alkenylation of 2-Alkyn-1-one O-Methyl Oximes

A palladium-catalyzed, cascade 5-endo-dig cyclization–alkenylation synthesis of isoxazoles has been developed. The addition of 1 equiv of n-Bu4NBr significantly increases the yield of the desired 4-alkenyl-3,4,5-trisubstituted isoxazoles. A variety of trisubstituted isoxazoles are prepared in moderate to excellent yields. One example of the synthesis of a naphthoisoxazole is reported by a cascade cyclization–alkenylation-Heck reaction.