Photocatalyzed Dearomative [2 + 2] Cycloaddition of Indoles with Alkynes to Access Cyclobutene-Fused Indolines
Yuanqi Luo1, Chaoyu Wang1, Zeng Han1
1Engineering Research Centre of Molecular Medicine of Ministry of Education, Key Laboratory of Fujian Molecular Medicine, Key Laboratory of Precision Medicine and Molecular Diagnosis of Fujian Universities, Key Laboratory of Xiamen Marine and Gene Drugs, Medical School, Huaqiao University, Xiamen, 361021, P. R. China.
Abstract:
Recently, energy-transfer-based photocatalytic cycloaddition has developed as an elegant strategy to overcome aromatic stabilization and achieve dearomatization of indole. However, these procedures mainly focus on the [2 + 2] cycloadditions of indoles with alkenes to build cyclobutane-fused indolines. The intermolecular [2 + 2] cycloaddition between indoles and internal alkynes remains less explored due to their potentially higher ring strain and thermodynamic instability. Herein, a general and efficient strategy has been developed via thioxanthone-catalyzed energy-transfer-driven [2 + 2] cycloaddition of indoles and alkynes. Various cyclobutene-fused indolines were provided in up to 95% yield for 25 examples with excellent stereoselectivity (>20:1 dr) under the mild reaction conditions. This protocol demonstrates remarkable features with simplicity of operation, broad substrate compatibility, high efficiency, excellent stereoselectivity, and exceptional atom and step economy. This study expands a previously underexplored energy-transfer-catalyzed intermolecular dearomative [2 + 2] cycloaddition of indoles with internal alkynes, enriching the compound library of strained-ring molecules.
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