Palladium Catalyzed ortho-C(sp2)–H Activation/Cyclization of Aryl Amines Assisted by Imine Directing Group and Vinylacetic Acid

Abstract

Abstract Palladium-catalyzed directed C − H functionalization/cyclization is an effective approach for synthesizing nitrogen heterocycles. Imine, known for its ease of installation/removal, has been extensively used in the C–H activation of aldehydes, ketones and alkylamines. Nevertheless, it been rarely explored in the C(sp2)–H activation of aryl amines because of the generation of a strained four-membered palladacycle. Herein, an imine directed palladium catalyzed C(sp2)–H functionalization of aryl amines assisted by vinylacetic acid has been established, providing access to a variety of γ-lactone fused tetrahydroquinolines under mild reaction conditions. The methodology demonstrates broad substrate scope and good functional group tolerance, representing notable advancement in organic synthesis. Mechanistic experiments were performed to clarify how the C(sp2)–H activation occurred, indicating the crucial role of vinylacetic acid. DFT calculations supported the observations, elucidating the strained four-membered ring C–H activation barrier was overcome via coordination and hydrogen bond interaction of vinylacetic acid.