Electrochemical dehydrogenative annulation for the synthesis of 4-oxo-oxazolines

Abstract

A metal- and oxidizing reagent-free electrochemical dehydrogenative annulation of enamides with O-nucleophiles has been developed, leading to a series of 4-oxo-oxazolines under environmentally friendly conditions. The present method demonstrates broad substrate scope and wide functional group tolerance. In addition to water, alcohols and carboxylic acids were also competent reaction partners. The merit of this electrochemical protocol has also been demonstrated by the gram-scale reaction and the synthesis of 2-(3,4-dimethoxyphenyl)-5-methyl-4,5-dihydrooxazol-4-ol (an antitumor nature product precursor). The mechanistic results suggest that the formation and homolytic cleavage of the N–Br bond is key to the success of this electrochemical dehydrogenative annulation reaction.