Copper(II)-Catalyzed Direct C3 Chalcogenylation of Indoles

3-Chalcogenylindoles serve as crucial building blocks in organic synthesis and pharmaceutical chemistry. Herein, we describe a simple and general synthesis of 3-chalcogenylindoles through the direct C–H chalcogenation of indoles using <i>N</i>-selenophthalimide and <i>N</i>-s...

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Main Authors: Liuyan Pan, Shengwei Chen, Dongfang Wu, Jian Shao, Xiaofeng Bao, Gong-Qing Liu
Format: Article
Language:English
Published: MDPI AG 2025-04-01
Series:Molecules
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Online Access:https://www.mdpi.com/1420-3049/30/9/1870
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author Liuyan Pan
Shengwei Chen
Dongfang Wu
Jian Shao
Xiaofeng Bao
Gong-Qing Liu
author_facet Liuyan Pan
Shengwei Chen
Dongfang Wu
Jian Shao
Xiaofeng Bao
Gong-Qing Liu
author_sort Liuyan Pan
collection DOAJ
description 3-Chalcogenylindoles serve as crucial building blocks in organic synthesis and pharmaceutical chemistry. Herein, we describe a simple and general synthesis of 3-chalcogenylindoles through the direct C–H chalcogenation of indoles using <i>N</i>-selenophthalimide and <i>N</i>-sulfenylsuccinimide as chalcogenation reagents in the presence of CuBr<sub>2</sub> as the catalyst. The reactions were carried out in CH<sub>2</sub>Cl<sub>2</sub> at room temperature under an air atmosphere with a low loading of catalyst, and a wide range of 3-selenylindoles and 3-thioindoles were obtained in good yields. Various functionalities, namely, methyl, methoxy, halo, ester, cyano, trifluoromethyl, and formyl groups on indoles, have shown amenability to the developed reaction. A mechanism involving the activation of the chalcogenation agent through CuBr<sub>2</sub> coordination with the amide carbonyl group is proposed.
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issn 1420-3049
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series Molecules
spelling doaj-art-6184d5c2536146db93155c7d149fdc602025-08-20T02:58:47ZengMDPI AGMolecules1420-30492025-04-01309187010.3390/molecules30091870Copper(II)-Catalyzed Direct C3 Chalcogenylation of IndolesLiuyan Pan0Shengwei Chen1Dongfang Wu2Jian Shao3Xiaofeng Bao4Gong-Qing Liu5Nantong Key Laboratory of Small Molecular Drug Innovation, School of Pharmacy, Nantong University, Nantong 226019, ChinaNantong Key Laboratory of Small Molecular Drug Innovation, School of Pharmacy, Nantong University, Nantong 226019, ChinaNantong Key Laboratory of Small Molecular Drug Innovation, School of Pharmacy, Nantong University, Nantong 226019, ChinaNantong Key Laboratory of Small Molecular Drug Innovation, School of Pharmacy, Nantong University, Nantong 226019, ChinaNantong Key Laboratory of Small Molecular Drug Innovation, School of Pharmacy, Nantong University, Nantong 226019, ChinaNantong Key Laboratory of Small Molecular Drug Innovation, School of Pharmacy, Nantong University, Nantong 226019, China3-Chalcogenylindoles serve as crucial building blocks in organic synthesis and pharmaceutical chemistry. Herein, we describe a simple and general synthesis of 3-chalcogenylindoles through the direct C–H chalcogenation of indoles using <i>N</i>-selenophthalimide and <i>N</i>-sulfenylsuccinimide as chalcogenation reagents in the presence of CuBr<sub>2</sub> as the catalyst. The reactions were carried out in CH<sub>2</sub>Cl<sub>2</sub> at room temperature under an air atmosphere with a low loading of catalyst, and a wide range of 3-selenylindoles and 3-thioindoles were obtained in good yields. Various functionalities, namely, methyl, methoxy, halo, ester, cyano, trifluoromethyl, and formyl groups on indoles, have shown amenability to the developed reaction. A mechanism involving the activation of the chalcogenation agent through CuBr<sub>2</sub> coordination with the amide carbonyl group is proposed.https://www.mdpi.com/1420-3049/30/9/1870chalcogenationindolesselenylindolessulfenylindolesCuBr<sub>2</sub>
spellingShingle Liuyan Pan
Shengwei Chen
Dongfang Wu
Jian Shao
Xiaofeng Bao
Gong-Qing Liu
Copper(II)-Catalyzed Direct C3 Chalcogenylation of Indoles
Molecules
chalcogenation
indoles
selenylindoles
sulfenylindoles
CuBr<sub>2</sub>
title Copper(II)-Catalyzed Direct C3 Chalcogenylation of Indoles
title_full Copper(II)-Catalyzed Direct C3 Chalcogenylation of Indoles
title_fullStr Copper(II)-Catalyzed Direct C3 Chalcogenylation of Indoles
title_full_unstemmed Copper(II)-Catalyzed Direct C3 Chalcogenylation of Indoles
title_short Copper(II)-Catalyzed Direct C3 Chalcogenylation of Indoles
title_sort copper ii catalyzed direct c3 chalcogenylation of indoles
topic chalcogenation
indoles
selenylindoles
sulfenylindoles
CuBr<sub>2</sub>
url https://www.mdpi.com/1420-3049/30/9/1870
work_keys_str_mv AT liuyanpan copperiicatalyzeddirectc3chalcogenylationofindoles
AT shengweichen copperiicatalyzeddirectc3chalcogenylationofindoles
AT dongfangwu copperiicatalyzeddirectc3chalcogenylationofindoles
AT jianshao copperiicatalyzeddirectc3chalcogenylationofindoles
AT xiaofengbao copperiicatalyzeddirectc3chalcogenylationofindoles
AT gongqingliu copperiicatalyzeddirectc3chalcogenylationofindoles