Carboxylic acids as double aryl group donors for biaryl synthesis

Abstract

The synthesis of biaryl compounds by employing carboxylic acids as double aryl group donors is reported. Naturally present and benign carboxylic acids have been applied as double aryl group donors by sequential decarbonylations for the construction of unsymmetrical biaryls. This method represents an orthogonal approach for the synthesis of valuable biaryl compounds. Aryl carboxylic acids were first converted into aryl boronic esters via palladium-catalyzed decarbonylative borylation. Next, aryl boronic esters were transformed into aryl boronic acids via hydrolysis. Biaryl compounds were generated through decarbonylative coupling between aryl carboxylic acids and aryl boronic acids. A broad substrate scope and excellent functional group tolerance have been demonstrated. Furthermore, a range of pharmaceutical motifs can be readily used in this approach with excellent yields. The present method successfully achieves the synthesis of highly valuable biaryls using readily available and inexpensive carboxylic acids as a single class of precursors to access cross-coupling synthons of central importance to the synthetic community.