Synthesis of Bis(heteroaryl) Ketones by Removal of Benzylic CHR and CO Groups

Abstract

A copper-catalyzed method for synthesis of diaryl ketones (Ar-CO-Ar') through removal of benzylic -CH2-, -CO-, and -CHR- groups from Ar-CO-CXR-Ar' has been discovered. A number of symmetrical and unsymmetrical heterocyclic ketones, which are usually difficult to synthesize, can be prepared in good to excellent yields. This method was applied to the synthesis of the nonsteroidal anti-inflammatory drug suprofen (47% yield over three steps). Based on preliminary mechanistic and kinetic studies, an active Cu/O2 species is proposed to mediate the rearrangement reaction.