Copper-mediated C-H activation/C-S cross-coupling of heterocycles with thiols

Sadananda Ranjit, Richmond Lee, Dodi Heryadi, Chao Shen, Jien Wu, Pengfei Zhang, Kuo-Wei Huang, Xiaogang Liu

Research output: Contribution to journalArticlepeer-review

230 Scopus citations

Abstract

We report the synthesis of a series of aryl- or alkyl-substituted 2-mercaptobenzothiazoles by direct thiolation of benzothiazoles with aryl or alkyl thiols via copper-mediated aerobic C-H bond activation in the presence of stoichiometric CuI, 2,2′-bipyridine and Na 2CO 3. We also show that the approach can be extended to thiazole, benzimidazole, and indole substrates. In addition, we present detailed mechanistic investigations on the Cu(I)-mediated direct thiolation reactions. Both computational studies and experimental results reveal that the copper-thiolate complex [(L)Cu(SR)] (L: nitrogen-based bidentate ligand such as 2,2′-bipyridine; R: aryl or alkyl group) is the first reactive intermediate responsible for the observed organic transformation. Furthermore, our computational studies suggest a stepwise reaction mechanism based on a hydrogen atom abstraction pathway, which is more energetically feasible than many other possible pathways including β-hydride elimination, single electron transfer, hydrogen atom transfer, oxidative addition/reductive elimination, and σ-bond metathesis. © 2011 American Chemical Society.
Original languageEnglish (US)
Pages (from-to)8999-9007
Number of pages9
JournalThe Journal of Organic Chemistry
Volume76
Issue number21
DOIs
StatePublished - Nov 4 2011

Bibliographical note

KAUST Repository Item: Exported on 2020-10-01
Acknowledgements: This study was supported in part by the Ministry of Education (MOE2010-T2-083), the Singapore Peking Oxford Research Enterprise (SPORE), the Science and Technology Plan of Zhejiang Province (2011C24004), and the Singapore-MIT alliance. X.L. is grateful to the National University of Singapore for the Young Research Award (C-143-000-022). R.L., D.H., and K.-W.H. are grateful for funding from KAUST and computing time from the NOOR computer cluster managed by the KAUST supercomputing team.

ASJC Scopus subject areas

  • Organic Chemistry

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