Anionic Domino C-O-Heterocyclization Approach for the Synthesis of 5-Vinyl Isoxazolines

Abstract: 5-Vinyl isoxazolines were isolated in high yields throughdomino nucleophilic addition–anionic C–O-heterocyclization,when allyl organometallics derived from trans-1,4-dihalobutenewere reacted with nitrile oxides. Key words: 1, 4-dihalobutene, nitrile oxide, 5-vinyl isoxazoline,organometallic addition 2-Isoxazolines are valuable heterocycles with a broadspectrum of pharmacological activities. They are alsouseful because of their potential as masked aldols, theunmasking of which can lead to useful synthetic interme-diates including b-amino alcohols or b-keto alcohols. 1 2-Isoxazolines are obtained mainly through the 1,3-dipolarcycloaddition of olefins to nitrile oxides and silylnitronates and to a lesser extent through the nitrosation ofcyclopropane accompanied by ring cleavage and cycliza-tion. 1d Of particular interest would be the synthesis of 5-vinyl isoxazolines which are valuable intermediates in thegeneration of a variety of biologically active molecules in-cluding D , L