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S-trifluoromethylation of thiols by hypervalent iodine reagents: a joint experimental and computational study


Sala, Oliver; Santschi, Nico; Jungen, Stefan; Lüthi, Hans Peter; Iannuzzi, Marcella; Hauser, Nicole; Togni, Antonio (2016). S-trifluoromethylation of thiols by hypervalent iodine reagents: a joint experimental and computational study. Chemistry - A European Journal, 22(5):1704-1713.

Abstract

The radical trifluoromethylation of thiophenol in condensed phase applying reagent 1 (3,3-dimethyl-1-(trifluoromethyl)-1λ(3),2-benziodoxol) has been examined by both theoretical and experimental methodologies. On the basis of ab initio molecular dynamics and metadynamics we show that radical reaction mechanisms favourably compete with polar ones involving the S-centred nucleophile thiophenol, their free energies of activation, ΔF(≠), lying between 9 and 15 kcal mol(-1). We further show that the origin of the proton activating the reagent is important. Hammett plot analysis reveals intramolecular protonation of 1, thus generating negative charge on the sulfur atom in the rate-determining step. The formation of a CF3 radical can be thermally induced by internal dissociative electron transfer, its activation energy, ΔF(≠), amounting to as little as 10.8 and 2.8 kcal mol(-1) for reagent 1 and its protonated form 2, respectively. The reduction of the iodine atom by thiophenol occurs either subsequently or in a concerted fashion.

Abstract

The radical trifluoromethylation of thiophenol in condensed phase applying reagent 1 (3,3-dimethyl-1-(trifluoromethyl)-1λ(3),2-benziodoxol) has been examined by both theoretical and experimental methodologies. On the basis of ab initio molecular dynamics and metadynamics we show that radical reaction mechanisms favourably compete with polar ones involving the S-centred nucleophile thiophenol, their free energies of activation, ΔF(≠), lying between 9 and 15 kcal mol(-1). We further show that the origin of the proton activating the reagent is important. Hammett plot analysis reveals intramolecular protonation of 1, thus generating negative charge on the sulfur atom in the rate-determining step. The formation of a CF3 radical can be thermally induced by internal dissociative electron transfer, its activation energy, ΔF(≠), amounting to as little as 10.8 and 2.8 kcal mol(-1) for reagent 1 and its protonated form 2, respectively. The reduction of the iodine atom by thiophenol occurs either subsequently or in a concerted fashion.

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8 citations in Web of Science®
7 citations in Scopus®
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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:07 Faculty of Science > Department of Chemistry
Dewey Decimal Classification:540 Chemistry
Language:English
Date:2016
Deposited On:16 Dec 2016 10:07
Last Modified:16 Dec 2016 11:32
Publisher:Wiley-VCH Verlag
ISSN:0947-6539
Publisher DOI:https://doi.org/10.1002/chem.201503774
PubMed ID:26742657

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