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

Shihui Liu, Aoxia Liu, Yongqiang Zhang, Wei Wang

Research output: Contribution to journalArticlepeer-review

58 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)4044-4050
Number of pages7
JournalChemical Science
Volume8
Issue number5
DOIs
StatePublished - 2017
Externally publishedYes

ASJC Scopus subject areas

  • Chemistry(all)

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