The Retro-Suzuki Reaction? A Palladium-Catalyzed Carbon-Carbon Decoupling of (Hetero)Biaryls

Abstract: We report the development of a novel C-C decoupling reaction mediated by a palladium/bis(phosphine) catalyst system. This methodology is the first of its kind, and allows for the chemoselective scission of Ar-Ar bonds to give aryl halides and arylboronic esters. Modest to good yields were obtained and the reaction exhibits high functional group tolerance. Notably, our conditions were effective in the late-stage functionalization of a Statin-class HMG-CoA reductase inhibitor. Detailed spectroscopic crystallographic studies were conducted to elucidate the mechanism by which this reaction occurs. These experiments revealed subtle facets of ligand and substrate electrostatics that are vital to the success of the reaction.