Electrophilic Aromatic Trifluoromethylthiolation with the Second Generation of Trifluoromethanesulfenamide

Abstract

Direct trifluoromethylthiolation of various aromatic and heteroaromatic compounds, variously substituted, can be performed with the second generation of trifluoromethanesulfenamide via a 'FriedelCrafts-like reaction'. This reaction requires mild conditions with a catalytic amount of protic or Lewis acid. Good results have been obtained, even with aromatic compounds bearing deactivating substituents.

Trifluoromethyl Sulfoxides: Reagents for Metal‐Free C−H Trifluoromethylthiolation

“…This triggered a push to develop shelf‐stable, easy‐to‐handle trifluoromethylthiolating agents (Scheme A) . Despite the advantages of these reagents, they are generally limited to the C−H trifluoromethylthiolation of highly electron‐rich (hetero)arenes, such as indoles and phenols, whereas reactions involving less nucleophilic arenes, such as anisole and toluene, are scarce . Furthermore, few reports describe the use of these reagents for the late‐stage trifluoromethylthiolation of complex molecules …”

“…In comparison to heteroarenes, the trifluoromethylthiolation of arenes has received less attention . Initial results using 1 a gave poor yields of the desired trifluoromethylthiolated arenes, however, a novel ester‐derived trifluoromethyl sulfoxide, 1 b , showed good reactivity (Scheme ).…”

Trifluoromethylthiolation of Arenes Using Lewis Acid and Lewis Base Dual Catalysis

“…A direct approach is the trifluoromethylthiolation of arene C–H bonds using electrophilic reagents. Since the development of the first electrophilic reagent, trifluoromethylsulfenyl chloride, which is gaseous and toxic, a wide range of more readily available, bench-stable CF 3 S-transfer reagents have been reported for trifluoromethylthiolation of arenes (Figure a). − Although many of these reagents are effective, methods involving N -trifluoromethylthiosaccharin ( 4 ) have been widely used for (hetero)­arene trifluoromethylthiolation. , The synthesis and application of N -trifluoromethylthiosaccharin ( 4 ) was first reported by Shen and co-workers, who demonstrated efficient trifluoromethylthiolation of N -heterocycles and electron-rich arenes using either trimethylsilyl chloride or triflic acid as an activator (Figure b) . Since this first report, modifications to accelerate the reaction or lower the temperature have been described using Lewis base catalysis or trifluoroethanol as a solvent .…”

Benzothiazolium salts as reagents for the deoxygenative perfluoroalkylthiolation of alcohols

“…In recent years, however, a selection of mostly electrophilic and radical sources has been introduced [27]. Nucleophilic perfluoroalkylthiolation is especially challenging due to the low nucleophilicity of heavily fluorinated thiolate anions and the potential for deleterious side-reactions resulting from β-fluoride elimination [28][29][30][31][32][33][34]. Only a handful of perfluoroalkylthiolate salts are known and, to the best of our knowledge, only one general direct nucleophilic perfluoroalkylthiolation of an alkyl electrophile has been reported to date [35].…”