Thermal-mediated catalyst-free heterolytic cleavage of 3-halooxindoles: rapid access to 3-functionalized-2-oxindoles

Abstract

Herein a previously unreported catalyst-free S_N1 reaction of the 3-halooxindoles to build 3-functionalized-2-oxindoles is described. The present protocol utilizes the thermal-mediated heterolytic cleavage of the 3-halooxindoles to generate a highly electrophilic 1-H-o-azaxylylene-1-ium A or 1-alkyl-o-azaxylylene-1-ium B intermediate as the Michael acceptor, avoiding the utilization of an additional base and metal as promoters, and providing a diversity-oriented approach to a series of 3-functionalized-2-oxindoles bearing a tetrasubstituted center in high yields (up to 93% yield). This method could provide libraries of structurally diverse and medicinally important small molecules that could aid the search for new bioactive molecules.