Practical, metal-free remote heteroarylation of amides via unactivated C(sp3 )-H bond functionalization

Chemical Science
Nana TangChen Zhu

Abstract

Development of practical methods for the production of multi-functionalized amides is one of the most important topics in both synthetic chemistry and drug discovery. Disclosed herein is a new, efficient, site-selective heteroarylation of amides via C(sp3)-H bond functionalization. Amidyl radicals are directly generated from the amide N-H bonds under mild conditions, which trigger the subsequent 1,5-HAT process. A wide scope of aliphatic amides including carboxamides, sulfonamides, and phosphoramides are readily modified at remote C(sp3)-H bonds by installing diverse heteroaryl groups. Borne out of pragmatic consideration, this protocol can be used for the late-stage functionalization of amides.

References

Jul 24, 2008·Chemical Society Reviews·Samir Z Zard
Jan 19, 2010·Chemical Reviews·Thomas W Lyons, Melanie S Sanford
Mar 18, 2011·Angewandte Chemie·Timothy Newhouse, Phil S Baran
Apr 21, 2011·Journal of Medicinal Chemistry·Stephen D Roughley, Allan M Jordan
Aug 14, 2012·Angewandte Chemie·Junichiro YamaguchiKenichiro Itami
Mar 20, 2013·Journal of the American Chemical Society·Zhaodong LiChaozhong Li
Apr 26, 2013·Beilstein Journal of Organic Chemistry·Béatrice Quiclet-Sire, Samir Z Zard
Mar 11, 2015·Accounts of Chemical Research·Olafs DaugulisLy Dieu Tran
May 29, 2015·Angewandte Chemie·Claudio Martínez, Kilian Muñiz
Jun 3, 2015·Journal of the American Chemical Society·Chendan ZhuZhuangzhi Shi
Jul 8, 2016·Angewandte Chemie·Ethan A WappesDavid A Nagib
Sep 16, 2016·Journal of the American Chemical Society·Ming YanPhil S Baran
Sep 28, 2016·Journal of the American Chemical Society·Brian J GroendykeSilas P Cook
Jan 21, 2017·Angewandte Chemie·Xiao-Qiang HuWen-Jing Xiao
Jun 22, 2017·Accounts of Chemical Research·Xi Wang, Armido Studer
Jul 13, 2017·Chemical Reviews·Jian HeJin-Quan Yu
Jul 26, 2017·Journal of the American Chemical Society·Ethan A WappesDavid A Nagib
Oct 13, 2017·Journal of the American Chemical Society·Dian-Feng ChenTomislav Rovis
May 15, 2018·Synthesis·Leah M StatemanDavid A Nagib
May 23, 2018·Chemistry : a European Journal·Jacob DaviesDaniele Leonori
Aug 8, 2018·Angewandte Chemie·Christina G Na, Erik J Alexanian
Apr 18, 2017·European Journal of Organic Chemistry·Luca Capaldo, Davide Ravelli
Feb 19, 2019·Chemical Science·Zuxiao ZhangDavid A Nagib
Apr 19, 2019·Chemical Science·Leah M StatemanDavid A Nagib

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Citations

Feb 6, 2020·Chemistry, an Asian Journal·Gautam KumarIndranil Chatterjee
Mar 21, 2020·Nature Communications·Quanping GuoZhaoqing Xu
Jan 18, 2020·Chemical Communications : Chem Comm·Zengqiang SongGuang Liang
Dec 23, 2020·Chemical Society Reviews·Rolando CannalireMariateresa Giustiniano
Jan 31, 2020·Chemical Science·Andrew D ChenDavid A Nagib
Jun 12, 2021·Angewandte Chemie·Lin WangArmido Studer
Dec 6, 2019·The Journal of Organic Chemistry·Zhiqiang DengGong Chen
Mar 25, 2020·Organic Letters·Qing-Qiang MinFeng Liu
Aug 24, 2019·The Journal of Organic Chemistry·Matthew M TierneyErik J Alexanian
Jul 3, 2020·Journal of the American Chemical Society·Yonghoon MoonSungwoo Hong
Sep 30, 2021·Chemical Reviews·Natalie Holmberg-Douglas, David A Nicewicz
Oct 1, 2021·Chemistry : a European Journal·Yong XiaArmido Studer

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Methods Mentioned

BETA
column chromatography

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