Due to the electron-richness of the C3/C2 positions of the indole moiety, direct nucleophilic bromination at the C5-position of tryptophol and tryptamine derivatives is difficult and remains unexplored. Herein, we...

The first example of cyclization cross-coupling of tryptophols and tryptamines has been realized by copper catalysis with air or oxone as the terminal oxidant, resulting in the direct construction of a new class of heterocyclic 3a,3a′-bisindolines in moderate to good yields with high chemoselectivities. A series of mechanistic control experiments were also conducted, indicating that the copper catalyst selectively coordinates with the nitrogen moiety of the tryptamine to initiate the oxidation, and a nucleophilic-alkylation process is proposed for the carbon−carbon bond-forming in the reaction. The novel synthetic strategies and molecular skeletons outlined in this work provide new ideas and concepts for the design of other useful reaction and potential drugs.

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....