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

S. Ranjit, R. Lee, D. Heryadi, C. Shen, J. Wu, P. Zhang, K.-W. Huang, X. Liu
J. Org. Chem., 76, pp. 8999-9007, (2011)

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

Keywords

CH bond activation

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 Na2CO3. 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.

Code

DOI: 10.1021/jo2017444

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