One-Pot Formation of CC and ON Bonds through Palladium-Catalyzed Dual C-H Activation: Synthesis of Phenanthridinones

摘要

Palladium-catalyzed OH activation has emerged in recent years as one of the most sustainable and intriguing protocols to construct OC, OO, ON, OS, and OX (X = halogen) bonds, and has been employed in the synthesis of pharmaceuticals and natural products. A directing group is commonly required to achieve high regioselectivity in a C-H activation reaction. Among the directing groups, the utilization of the CONHOMe group in the arylation of sp~3 C-H bonds through palladium-catalyzed C-C bond formation was first discovered by Yu and co-workers.Subsequently, Wasa and Yu exploited the same directing group in intramolecular cyclization reactions, thus affording lactam derivatives through the palladium-catalyzed formation of ON bonds. Nevertheless, the cascade formation of C-C and ON bonds through palladium-catalyzed C-H activation in one pot is quite challenging. In continuation of our interest in the OH activation of N-methoxybenzamides, we envision that a palladium-catalyzed intermolecular C-C bond formation could be coupled with another palladium-catalyzed intramolecular C-N bond formation for a rapid synthesis of biologically important phenanthridinones (Scheme 1). Herein we report the one-pot cascade synthesis of phenanthridinones by the palladium-catalyzed reaction of N-methoxybenza-mides and aryl iodides with this strategy. This reaction results in the breaking of four bonds and formation of two bonds.