Copper-catalyzed oxidative selective cyclization/C-N cross-coupling of two tryptamines to access 3a-tryptamine-pyrroloindolines

Transition-metal-catalyzed C-N bond formation reactions have been widely studied in recent decades, but site-selective intermolecular C-N cross-coupling between the carbon and nitrogen sites of two identical molecules is less explored. Herein, we report the highly selective copper-catalyzed oxidative cyclization/C-N cross-coupling of two tryptamines with O-2 as the terminal oxidant, which provides practical and direct access to a new class of indole-linked-pyrroloindoline compounds in moderate to good yields. Mechanistic studies suggested that the coordination between the copper catalyst and the tryptamine substrate is key for chemoselectivity control.

Automated summary

Transition-metal-catalyzed C-N bond formation reactions have been extensively studied, but the site-selective intermolecular C-N cross-coupling between identical molecules is relatively unexplored. In this study, we present a highly selective copper-catalyzed oxidative cyclization/C-N cross-coupling of two tryptamines using O-2 as the terminal oxidant, providing a practical and direct route to a new class of indole-linked-pyrroloindoline compounds in moderate to good yields. Mechanistic studies revealed that the coordination between the copper catalyst and the tryptamine substrate is crucial for controlling chemoselectivity.