A general palladium-catalyzed carbonylative synthesis of α-CF3-substituted ketones and carboxylic acid derivatives

Abstract

α-CF3-substituted carboxylic acid derivatives have drawn wide attention owing to their importance for both pharmaceutical and synthetic communities. However, methodologies for their construction are still very limited. Herein, we developed a general palladium-catalyzed carbonylative procedure for the synthesis of α-CF3-substituted ketones and carboxylic acid derivatives. With amines, phenols, alcohols, arylboronic acids, and even less-nucleophilic sulfonamides and amides as the reaction partners, the corresponding amides, esters, ketones and imides were obtained in good yields with excellent functional group tolerance. Furthermore, this protocol has also been applied to the late-stage modification of 25 densely functionalized pharmaceutical agents and natural products.