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

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. Carbon-carbon bonds constitute the basic foundation of synthetic chemistry. Protocols for the generation and cleavage of such bonds are indispensable for the synthesis of new organic scaffolds. Although carbon-carbon bond-formation techniques have been studied extensively, the cleavage of carbon-carbon bonds is still a difficult objective. The inert nature of the carbon-carbon bond makes its cleavage problematic, and gaining control of it is even more challeng