Issue 2, 2017

The dual role of thiourea in the thiotrifluoromethylation of alkenes

Abstract

Alkenes substituted with a thiourea undergo C–CF3 followed by intramolecular C–S bond formation with the Togni reagent and trifluoroacetic acid (TFA) at room temperature; thiols and thioamides are not suitable S-sources for this reaction. This anti-addition process involves a CF3 radical, and affords CF3-substituted thiazolines and thiazines for medicinal applications. A metal or photoredox catalyst is not required as the thiourea acts as a reductant, as well as serving as an S-source capable of adding to a C-centered radical. Mechanistic work comparing the reactivity of thiourea, urea, thioamide and thiol in the context of alkene trifluoromethylation demonstrates that in this series, the thiourea is unique for its ability to release CF3 radical from the Togni reagent, and to orchestrate trifluoromethylation followed by S-cyclization with both activated and unactivated alkenes.

Graphical abstract: The dual role of thiourea in the thiotrifluoromethylation of alkenes

Supplementary files

Article information

Article type
Edge Article
Submitted
23 Jun 2016
Accepted
30 Sep 2016
First published
30 Sep 2016
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY license

Chem. Sci., 2017,8, 1195-1199

The dual role of thiourea in the thiotrifluoromethylation of alkenes

P. Ricci, T. Khotavivattana, L. Pfeifer, M. Médebielle, J. R. Morphy and V. Gouverneur, Chem. Sci., 2017, 8, 1195 DOI: 10.1039/C6SC02790C

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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