Ricci Paolo, Khotavivattana Tanatorn, Pfeifer Lukas, Médebielle Maurice, Morphy John Richard, Gouverneur Véronique
Chemistry Research Laboratory , Department of Chemistry , Oxford University , OX1 3TA , UK . Email:
Université de Lyon , Université Claude Bernard Lyon I , ICBMS UMR CNRS - UCBL - CPE - INSA 5246 , Equipe Synthèse de Molécules d'Intérêt Thérapeutique (SMITh) , 43 bd du 11 Novembre 1918 , Villeurbanne 69622 , France.
Chem Sci. 2017 Feb 1;8(2):1195-1199. doi: 10.1039/c6sc02790c. Epub 2016 Sep 30.
Alkenes substituted with a thiourea undergo C-CF 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 CF radical, and affords CF-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 CF radical from the Togni reagent, and to orchestrate trifluoromethylation followed by -cyclization with both activated and unactivated alkenes.
被硫脲取代的烯烃在室温下与托格尼试剂和三氟乙酸（TFA）发生碳-碳氟键形成反应，随后发生分子内碳-硫键形成；硫醇和硫代酰胺不适用于此反应的硫源。这种反加成过程涉及一个碳氟自由基，并为药物应用提供碳氟取代的噻唑啉和噻嗪。不需要金属或光氧化还原催化剂，因为硫脲既作为还原剂，又作为能够加成到碳中心自由基上的硫源。在烯烃三氟甲基化的背景下比较硫脲、尿素、硫代酰胺和硫醇反应性的机理研究表明，在这个系列中，硫脲因其能够从托格尼试剂中释放碳氟自由基，并能协调三氟甲基化反应，随后与活化和未活化的烯烃进行环化反应而独具特色。
