Late-Stage Chemo- and Enantioselective Oxidation of Indoles to C3-Monosubstituted Oxindoles

Song Li, Xigong Liu*, Chen-Ho Tung, Lei Liu*

*School of Chemistry and Chemical Engineering, Shandong University, Jinan 250100, China, Email: xigongliusdu.edu.cn, leiliusdu.edu.cn

S. Li, X. Liu, C.-H. Tung, L. Liu, J. Am. Chem. Soc., 2023, 145, 27120-27130.

DOI: 10.1021/jacs.3c11742

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Abstract

The synthesis of chiral 3-monosubstituted oxindoles is a significant challenge due to the ease of racemization. A mild titanium-catalyzed chemo- and enantioselective indole oxidation provides a diverse set of chiral 3-monosubstituted oxindoles with excellent yields and ees in the presence of H₂O₂ as green terminal oxidant. The reaction tolerates a broad range of functional groups.

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proposed mechanism

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General procedure for asymmetric indole oxidation

To a solution of indole (1 equiv, 0.1 mmol) in EtOAc (1.0 mL) was added 30% aqueous H₂O₂ (1.2 equiv) and catalyst (0.1 mmol %) at room temperature. The reaction was stirred for 12-24 h, and monitored by TLC analysis. Then the reaction was concentrated under reduced pressure and directly purified by silica gel chromatography (EtOAc/petroleum ether) to give the desired product.

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Key Words

oxindoles, hydrogen peroxide

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ID: J48-Y2023