Highly pH-Mediated Chemoselective Ir-Catalyzed Cascade Reductive Cyclization of 2-Ethynylbenzaldehyde with Arylamines

Isoindolines and 1,2-dihydroisoquinolines are important building blocks in drug molecules, agrochemicals, and materials. Herein, a novel and efficient pH-mediated selective Ir-catalyzed cascade reductive cyclization of 2-ethynylbenzaldehyde by coupling with aryl amines was realized. Using HCOOH as the hydride donor at low pH (1-2) in H2O media, the isoindoline products were obtained exclusively, while 1,2-dihydroisoquinoline products were formed preferentially by employing HCOONa as the hydride donor at high pH (9-10) using DMF as solvent. A wide range of functional groups, including electron-rich as well as electron-poor substituents on the aryl group of 2-ethynylbenzaldehyde and aryl amines, can be tolerated, affording the corresponding products in moderate to good yields. The practicality of this sustainable process was evidenced by large-scale experiment. Our mechanistic investigations indicate that the pH value is critical to the chemoselectivity.