Microwave-assisted synthesis of a [3+2] cycloaddition library

Abstract

A novel method for the synthesis of a library of substituted prolines utilizing microwave-assisted synthesis is described. The process involves rapid microwave irradiation of α-aminoesters and aldehydes to generate imines followed by the addition of a dipolarophile and subsequent irradiation to produce the [3+2] cycloadducts. The decrease in reaction time afforded by microwave irradiation allowed for the production of an 800-membered solution-phase library in twofold less time than by traditional thermal methods. These products were purified by solid-supported reagent scavenging to furnish the desired products in high yields and purity.