The dual role of thiourea in the thiotrifluoromethylation of alkenes

被引:41
作者
Ricci, Paolo [1 ]
Khotavivattana, Tanatorn [1 ]
Pfeifer, Lukas [1 ]
Medebielle, Maurice [2 ]
Morphy, John Richard [3 ]
Gouverneur, Veronique [1 ]
机构
[1] Univ Oxford, Dept Chem, Chem Res Lab, Oxford OX1 2JD, England
[2] Univ Claude Bernard Lyon I, CNRS, UMR, F-69622 Villeurbanne, France
[3] Eli Lilly & Co Ltd, Med Chem, Windlesham GU206PH, Surrey, England
关键词
COPPER-CATALYZED TRIFLUOROMETHYLATION; UNACTIVATED ALKENES; ELECTROPHILIC TRIFLUOROMETHYLATION; OLEFINIC TRIFLUOROMETHYLATION; RADICAL TRIFLUOROMETHYLATION; BIOLOGICAL EVALUATION; MEDICINAL CHEMISTRY; SALT SYSTEM; HYDROTRIFLUOROMETHYLATION; OXYTRIFLUOROMETHYLATION;
D O I
10.1039/c6sc02790c
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
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.
引用
收藏
页码:1195 / 1199
页数:5
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