Metal-Free Electrophilic Trifluoroethylthiolation with NaSO₂CH₂CF₃

Abstract

Metal-free trifluoroethylthiolation with fluorinated sulfinate salt NaSOCHCF under reductive conditions has been developed. The strategy enables the installation of the SCHCF moiety efficiently to form a number of unexplored stable trifluoroethylthiolated heterocycles, arenes, and thiols, which have the potential to be a new series of fluorine-containing chemical entities for medicinal chemists.

Methylthiolation for Electron‐Rich Heteroarenes with DMSO‐TsCl

“…It was found that 64 % yield of the product was achieved when 1.0 equiv. of TsCl was utilized (entries [5][6][7][8]. The effects of different solvents in the reaction were then investigated and cyclohexane was selected as the most suitable solvent for this transformation (entries 9-12).…”

“…[1] Especially heteroaromatic sulfides and their derivatives play significant roles in medicinal chemistry and drug development ( Figure 1). [2] Additionally, heteroaromatic sulfides can be further transformed into thiols, [3] sulfoxides, [4] sulfones, [5] and applied to cross-coupling reaction. [6] The formation of CÀ S bond has attracted extensive attention from chemists in recent ten years.…”

Copper(II)-Catalyzed Direct C–H Trifluoroethylation of Heteroarenes

“…12 Yi and co-workers reported the synthesis of CF 3 CH 2 SO 2 Na first and used this reagent for trifluoroethylthiolation at the C-3 position of indoles in 2018. 13 On the basis of Yi's research, we tried to use the reagent to achieve trifluoroethylation of the C-2 position of indoles (Figure 2f). Herein, we reported a new method to synthesize CF 3 CH 2 SO 2 Na, which could be prepared simply from 2mercaptobenzothiazole and CF 3 CH 2 I on a large scale in 58% yield [eq 1].…”

“…In the same year, Weng and co-workers developed a simple method for the synthesis of 2-(2,2,2-trifluoroethyl)-substituted indoles through a one-pot sequence (Figure e) . Yi and co-workers reported the synthesis of CF 3 CH 2 SO 2 Na first and used this reagent for trifluoroethylthiolation at the C-3 position of indoles in 2018 . On the basis of Yi’s research, we tried to use the reagent to achieve trifluoroethylation of the C-2 position of indoles (Figure f). …”

Bunte Salt CH2FSSO3Na: An Efficient and Odorless Reagent for Monofluoromethylthiolation

“…Due to the masked effect and their high stability and being odorless, they have been widely used in the development of sulfides as sulfur sources . Inspired by these seminal works and our continuous research interests in fluorine-containing sodium salts, we decided to disclose a typical Bunte salt, sodium S -(fluoromethyl) sulfurothioate, that could be a potential monofluoro­methyl­thiolating reagent.…”