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Synlett 2020; 31(04): 363-368
DOI: 10.1055/s-0039-1691567
letter
© Georg Thieme Verlag Stuttgart · New York

Metal-Free Regioselective Alkylation of Imidazo[1,2-a]pyridines with N-Hydroxyphthalimide Esters under Organic Photoredox Catalysis

Bin Sun
a   Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou 310014, P. R. of China
c   National Engineering Research Center for Process Development of Active Pharmaceutical Ingredients, Zhejiang University of Technology, Hangzhou 310014, P. R. of China   Email: jincan@zjut.edu.cn
,
Tengwei Xu
b   College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou 310014, P. R. of China   Email: jincan@zjut.edu.cn
c   National Engineering Research Center for Process Development of Active Pharmaceutical Ingredients, Zhejiang University of Technology, Hangzhou 310014, P. R. of China   Email: jincan@zjut.edu.cn
,
Liang Zhang
b   College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou 310014, P. R. of China   Email: jincan@zjut.edu.cn
c   National Engineering Research Center for Process Development of Active Pharmaceutical Ingredients, Zhejiang University of Technology, Hangzhou 310014, P. R. of China   Email: jincan@zjut.edu.cn
,
Rui Zhu
b   College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou 310014, P. R. of China   Email: jincan@zjut.edu.cn
c   National Engineering Research Center for Process Development of Active Pharmaceutical Ingredients, Zhejiang University of Technology, Hangzhou 310014, P. R. of China   Email: jincan@zjut.edu.cn
,
Jin Yang
b   College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou 310014, P. R. of China   Email: jincan@zjut.edu.cn
c   National Engineering Research Center for Process Development of Active Pharmaceutical Ingredients, Zhejiang University of Technology, Hangzhou 310014, P. R. of China   Email: jincan@zjut.edu.cn
,
Min Xu
a   Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou 310014, P. R. of China
c   National Engineering Research Center for Process Development of Active Pharmaceutical Ingredients, Zhejiang University of Technology, Hangzhou 310014, P. R. of China   Email: jincan@zjut.edu.cn
,
Can Jin∗
a   Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou 310014, P. R. of China
b   College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou 310014, P. R. of China   Email: jincan@zjut.edu.cn
c   National Engineering Research Center for Process Development of Active Pharmaceutical Ingredients, Zhejiang University of Technology, Hangzhou 310014, P. R. of China   Email: jincan@zjut.edu.cn
› Author AffiliationsThis work was supported by the National Natural Science Foundation of China (21606202) and Natural Science Foundation of Zhejiang Province (LY15B060007). We are also grateful to the College of Pharmaceutical Sciences, Zhejiang University of Technology and Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals for the financial help.
Further Information

Publication History

Received: 14 November 2019

Accepted after revision: 29 December 2019

Publication Date:
14 January 2020 (online)

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Abstract

A visible-light-induced direct C–H alkylation of imidazo[1,2-a]pyridines has been developed. It proceeds at room temperature by employing inexpensive Eosin Y as a photocatalyst and alkyl N-hydroxyphthalimide (NHP) esters as alkylation reagents. A variety of NHP esters derived from aliphatic carboxylic acids (primary, secondary, and tertiary) were tolerated in this protocol, giving the corresponding C-5-alkylated products in moderate to excellent yields. Mechanistic studies indicate that a radical decarboxylative coupling pathway was involved in this process.

Key words

photocatalysis - C–H alkylation - NHP esters - regioselectivity - metal-free reactions

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/s-0039-1691567.
  • Supporting Information
 

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