Direct Cα-heteroarylation of structurally diverse ethers via a mild N -hydroxysuccinimide mediated cross-dehydrogenative coupling reaction

Chemical Science
Shihui LiuWei Wang

Abstract

An important challenge in the Cα-heteroarylation of ethers is the requirement of a large excess amount of ethers (that are used as solvents in many cases) to achieve effective transformations. This drawback has significantly restricted the Cα-heteroarylation of ethers to the use of simple and easily accessible ether substrates. To overcome this limitation, a new, efficient, N-hydroxysuccinimide (NHS) mediated, mild and metal-free CDC strategy for the direct Cα-heteroarylation of diverse ethers has been developed. Different to our previous benzaldehyde mediated photoredox Cα-heteroarylation, we have identified NHS as a new and efficient mediator without using light. A distinct non-photoredox engaged hydrogen-atom-transfer (HAT) mechanism that used a nitrogen-centered radical cation produced from NHS is initially revealed. Notably, only 5-10 equivalents of ethers as coupling partners are used, which allows for structurally diverse and complex ethers to engage in this process, to create highly medicinally relevant Cα-heteroarylated ethers. Furthermore, more structurally diverse heterocyclics can serve as reactants for this process.

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Aug 15, 2018·Angewandte Chemie·Gwilherm Evano, Cédric Theunissen
Apr 16, 2019·Chemistry : a European Journal·Yueteng ZhangWei Wang
Feb 23, 2020·Organic & Biomolecular Chemistry·Linhua ShenYusheng Wu
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Mar 7, 2018·The Journal of Organic Chemistry·Zheng LuoDongen Lin
Jan 16, 2019·The Journal of Organic Chemistry·Kishor D ManeGurunath Suryavanshi
Sep 25, 2017·Organic Letters·Marcos San SegundoArkaitz Correa
Nov 29, 2017·Organic Letters·Bingyu LiangZhong-Quan Liu
Aug 26, 2021·Organic Letters·Manotosh BhakatJoyram Guin
Jan 7, 2020·Journal of the American Chemical Society·He HuangTristan H Lambert
Aug 24, 2019·The Journal of Organic Chemistry·Chia-Yu HuangChao-Jun Li

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