Pd-Catalyzed Aerobic Oxidative Heck Cross-Coupling for the Straightforward Construction of Indole δ-Lactams

The [6.5.6]-tricyclic indole δ-lactam represents a common key intermediate for the synthesis of a broad variety of structurally intriguing indole alkaloids. The development of a method for the versatile and straightforward construction of such structural motif is of great importance for potential synthetic applications. Herein, we present a co-ligand-prompted Pd-catalyzed 6-exo-trig intramolecular cyclization of indolyl amides via the aerobic oxidative Heck cross-coupling. The method provided a general and efficient way for the construction of [6.5.6]-tricyclic indole δ-lactams. A mechanistic study suggests that a Pd((I))/Pd((III)) catalytic cycle should be responsible for effective coupling, which represents a mechanistically alternative pathway when compared with the Pd((0))/Pd((II)) cycle proposed for other related coupling reactions.