Copper-Catalyzed Selective Oxidative Cross-Coupling of Tryptophols and Tryptamines To Access Heterocyclic 3a,3a′-Bisindolines

Thefirst example of cyclization cross-coupling oftryptophols and tryptamines has been realized by copper catalysiswith air or oxone as the terminal oxidant, resulting in the directconstruction of a new class of heterocyclic 3a,3a '-bisindolines inmoderate to good yields with high chemoselectivities. A series ofmechanistic control experiments were also conducted, indicatingthat the copper catalyst selectively coordinates with the nitrogenmoiety of the tryptamine to initiate the oxidation, and anucleophilic-alkylation process is proposed for the carbon-carbonbond-forming in the reaction. The novel synthetic strategies andmolecular skeletons outlined in this work provide new ideas and concepts for the design of other useful reaction and potential drugs.

Automated summary

The first example of cyclization cross-coupling of tryptophols and tryptamines has been achieved by copper catalysis, resulting in the direct construction of a new class of heterocyclic 3a,3a'-bisindolines. Mechanistic control experiments revealed that the copper catalyst selectively coordinates with the nitrogen moiety of the tryptamine, initiating the oxidation, and a nucleophilic-alkylation process is proposed for the carbon-carbon bond formation.