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

Abstract

SummaryThe [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.