Copper-mediated C-H activation/C-S cross-coupling of heterocycles with thiols
KAUST DepartmentPhysical Sciences and Engineering (PSE) Division
Chemical Science Program
KAUST Supercomputing Laboratory (KSL)
KAUST Catalysis Center (KCC)
Biological and Environmental Sciences and Engineering (BESE) Division
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AbstractWe 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.
SponsorsThis 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.
PublisherAmerican Chemical Society (ACS)
JournalThe Journal of Organic Chemistry
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