Copper-Catalyzed Selective Electron Transfer Enables Switchable Divergent Synthesis of 3-Functionalized Oxindoles

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 (O2) 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.

Automated summary

We report a copper-catalyzed selective single-electron transfer strategy for the oxidative rearrangement of 3-substituted indoles using air as the terminal oxidant. This method provides a streamlined approach to access 3-hydroxyl-, 3-alkoxyl-, and 3-hygrogenous-2-oxindoles via a 3-radical-2-hydroxyl indoline intermediate. The protocol demonstrates high chemoselectivity, good functional group tolerance, and broad application potential in the modular synthesis of biologically 3-functionalized oxindole derivatives.