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Synthesis 2017; 49(22): 5017-5024
DOI: 10.1055/s-0036-1589073
paper
© Georg Thieme Verlag Stuttgart · New York

K2S2O8-Activated Friedel–Crafts Type Alkylation of Indoles with α-Amido Sulfones

Xiaoyan Wu
Innovative Drug Research Centre, School of Pharmaceutical Sciences, Chongqing University, No.55 Daxuecheng, South Rd., Shapingba, Chongqing 401331, P. R. of China   Email: wenling.qin@cqu.edu.cn
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Lu Xue
Innovative Drug Research Centre, School of Pharmaceutical Sciences, Chongqing University, No.55 Daxuecheng, South Rd., Shapingba, Chongqing 401331, P. R. of China   Email: wenling.qin@cqu.edu.cn
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Shilong Luo
Innovative Drug Research Centre, School of Pharmaceutical Sciences, Chongqing University, No.55 Daxuecheng, South Rd., Shapingba, Chongqing 401331, P. R. of China   Email: wenling.qin@cqu.edu.cn
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Shiqi Jia
Innovative Drug Research Centre, School of Pharmaceutical Sciences, Chongqing University, No.55 Daxuecheng, South Rd., Shapingba, Chongqing 401331, P. R. of China   Email: wenling.qin@cqu.edu.cn
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Jun Ao
Innovative Drug Research Centre, School of Pharmaceutical Sciences, Chongqing University, No.55 Daxuecheng, South Rd., Shapingba, Chongqing 401331, P. R. of China   Email: wenling.qin@cqu.edu.cn
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Wenling Qin*
Innovative Drug Research Centre, School of Pharmaceutical Sciences, Chongqing University, No.55 Daxuecheng, South Rd., Shapingba, Chongqing 401331, P. R. of China   Email: wenling.qin@cqu.edu.cn
› Author AffiliationsThis work was supported by the Fundamental Research Funds for the Central Universities (Grant No. 0903005203479), NSFC (21402016).
Further Information

Publication History

Received: 20 April 2017

Accepted after revision: 14 June 2017

Publication Date:
25 July 2017 (online)

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Abstract

A K2S2O8-activated regioselective alkylation of α-amido sulfones at the C-3 position of indoles is reported. The protocol developed herein provides an alternative new strategy to the previous approach by using Lewis acid, clay, and resin as catalyst for this Friedel–Crafts type alkylation of indoles with α-amido sulfones. The formed product bears a versatile transformable sulfone group and an amino group. The reaction condition is tolerant to a wide range of substrates, including a series of indoles with electron-withdrawing and electron-donating groups at different positions. Moreover, a variety of α-substituted phenylamido sulfones and some α-aliphatic amido sulfones also give the desired products in modest yield. Furthermore, a preliminary mechanism study was performed and the plausible reaction mechanism is discussed.

Key words

K2S2O8 - indole alkylation - α-amido sulfone - Friedel–Crafts reaction