Asymmetric Synthesis of Functionalized 2-Isoxazolines

Abstract

The asymmetric synthesis of the isoxazoline skeleton was achieved by the oxidation of hydroxylaminoalkyl furan prepared from simple starting materials: 2-methylfuran and (S)-epichlorohydrin. The synthesis features an NBS-mediated oxidation of hydroxylaminoalkyl furan to give an alpha,beta-unsaturated ketone intermediate which cyclized to the isoxazoline. The alpha,beta-unsaturated double bond was successfully cleaved with RuCl3xH2O catalysis en route to the isoxazoline skeleton bearing alcohol, aldehyde, and carboxylic acid functionalities.