S‐Trifluoromethylation of Thiols by Hypervalent Iodine Reagents: A Joint Experimental and Computational Study. Issue 5 (7th January 2016)

• Record Type: Journal Article
• Authors: Sala, Oliver; Santschi, Nico; Jungen, Stefan; Lüthi, Hans Peter; Iannuzzi, Marcella; Hauser, Nicole; Togni, Antonio
• Is Part Of: Chemistry. Volume 22:Issue 5(2016)
• Page Start: 1704
• Page End: 1713
• Publication Date: 2016-01-07
• Subjects: ab initio calculations -- hypervalent iodines -- linear free energy relationship -- radical reactions -- trifluoromethylation; Chemistry -- Periodicals; 540
• DOI: 10.1002/chem.201503774
• Languages: English
• ISSNs: 0947-6539

Abstract

Abstract: The radical trifluoromethylation of thiophenol in condensed phase applying reagent1 (3, 3‐dimethyl‐1‐(trifluoromethyl)‐1 λ 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, Δ F ≠, 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 of1, 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, Δ F ≠, amounting to as little as 10.8 and 2.8 kcal mol −1 for reagent1 and its protonated form2, respectively. The reduction of the iodine atom by thiophenol occurs either subsequently or in a concerted fashion. Abstract : Radical moves : The radical trifluoromethylation of thiophenol in condensed phase applying 3, 3‐dimethyl‐1‐(trifluoromethyl)‐1 λ 3, 2‐benziodoxol has been examined by theoretical and experimental methodologies. The results show a strong evidence that S ‐trifluoromethylation of thiophenol by λ 3 ‐iodanes follows a radical pathway.