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Cercosporin-Photocatalyzed [4+1]- and [4+2]-Annulations of Azoalkenes Under Mild Conditions
Published on: July 17, 2020
Synthesis of Semi-Saturated Heterocycles via Photocatalytic Intramolecular [2 + 2] Cycloaddition/Dearomatization
Zeng Han1, Jiayin Wang1, Hong Zhang1
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, School of Biomedical Sciences, Huaqiao University, Xiamen 361021, P. R. China.
Abstract:
Intramolecular [2 + 2] cycloaddition/dearomatization could be an ideal pathway to construct semi-saturated polycycles in a "one-pot" manner. However, such a reaction is considered as thermodynamically infeasible due to the instability of the cyclobutane-fused rings and the higher triplet-excited-energy barrier of substrates. Herein, we successfully achieved an array of semi-saturated alkaloid analogues─cyclobutane-fused indolizidines─in up to 98% yield for 33 examples through intramolecular [2 + 2] cycloaddition of indoles via high-energy diradical intermediates. This reaction was initiated by a visible-light-induced energy transfer strategy, exhibited excellent chem-, regio-, and stereoselectivity (>99:1 dr), and provided an easy access for rapid late-stage saturation of pharmaceutical indole-containing molecules.
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