A novel synthesis of various fused perfluoroalkylated 2,3-dihydroisoxazoles has been achieved via the oxa-Michael-aldol [3+2] annulation between perfluoroalk-2-ynoates and N-hydroxyimides. The reactions were found to undergo a pathway to provide the pyrrolidin-2-one fused perfluoroalkylated 2,3-dihydroisoxazoles. This transformation thus offers a rapid and efficient entry to diverse pharmaceutically attractive polycyclic scaffolds under mild catalyst-free conditions in up to 97% yield.