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...

Oxidative rearrangement of 3-substituted indoles is a fundamental organic transformation for the synthesis of 2-oxindole scaffolds. However, this time-consuming and complex task produces a single type of product via two-electron oxidation using stoichiometric chemical oxidants. Herein, we report a unified and efficient copper-catalyzed selective single-electron transfer strategy for three oxidation reactions of 3-substituted indoles using air (O 2 ) as the terminal oxidant, providing a streamlined and practical synthetic approach to access 3-hydroxyl-, 3-alkoxyl-, and 3hygrogenous-2-oxindoles via a 3-radical-2-hydroxyl indoline intermediate. This copper catalysis protocol demonstrates high chemoselectivity, good functional group tolerance, and broad application potential in the modular synthesis of biologically 3-functionalized oxindole derivatives.

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.