Pd-Catalyzed Direct Deoxygenative Arylation of Non-π-Extended Benzyl Alcohols with Boronic Acids via Transient Formation of Non-Innocent Isoureas

Abstract

We report the direct arylation of non-derivatized alcohols with boronic acids and demonstrate that a Pd catalyst, in combination with a carbodiimide, can be used to forge a C–C bond via the transient formation of non-innocent isoureas from the corresponding alcohols. Besides further polarizing the C–O bond, the transiently generated isourea contains a masked base that is released during the reaction to enable catalytic turnover under exogenous base-free conditions. The developed concept was benchmarked against the coupling of non-π-extended benzyl alcohols and boronic acids and led to the formation of a C–C bond between differently decorated coupling partners. Notably, the strategic generation of non-innocent isoureas endows this C–O cleavage reaction with high orthogonality over conventional electrophiles and enables the employment of highly base-sensitive boronic acids. Additionally, the preformed isoureas can be leveraged for rapid (5 min reaction time) exogenous base-free coupling reactions, which work under conventional thermal conditions and do not rely on customized catalysts or specialized equipment. The synthetic investigations were also complemented by preliminary mechanistic studies. More broadly, the presented work bridges a conceptual gap between two important research areas, that is, carbodiimide-mediated alcohol activation and deoxygenative transition metal-catalyzed coupling chemistry, providing a promising blueprint for direct catalytic deoxygenative reactions.