Tert-butyl nitrite-mediated domino synthesis of isoxazolines and isoxazoles from terminal aryl alkenes and alkynes

Abstract

A sequential construction of C–C, C–O, C = N, and C = O bonds from alkenes leading to the direct synthesis of isoxazolines in the presence of tert-butyl nitrite, quinoline and the Sc(OTf)₃ catalyst in DCE at 80°C has been accomplished. An unprecedented three consecutive C–H functionalizations of two styrenes are involved in this isoxazoline synthesis. In this radical-mediated reaction, one-half of the aryl alkene is converted into an intermediate 2-nitroketone, which serves as a 1,3-dipolarophile and undergoes cycloaddition with the other half of the unreacted aromatic terminal alkene. The use of an alkyne in lieu of an alkene leads to the formation of isoxazole under identical reaction conditions.