Electrochemical synthesis of oxazoles via a phosphine-mediated deoxygenative [3 + 2] cycloaddition of carboxylic acids

Abstract

A direct electrochemical phosphine-mediated deoxygenative [3 + 2] cycloaddition strategy for oxazole synthesis is described, employing naturally abundant and inexpensive carboxylic acids as starting materials. This method is performed in a green and sustainable catalytic system, and avoids the use of transition metals and toxic oxidants. Good functional group tolerance, the success of gram-scale experiments and the late-stage modification of drug molecules greatly highlight the potential applicability of our method. Mechanistic studies suggest that an acyloxyphosphonium ion is generated as a key intermediate via anodic oxidation, followed by nucleophilic substitution and cycloaddition with isocyanide.