Perfluoroalkylation of Thiosulfonates: Synthesis of Perfluoroalkyl Sulfides

Abstract

A practical synthesis of perfluoroalkyl sulfides is described. The method employs stable and readily accessible thiosulfonates as new electrophiles with commercial nucleophilic perfluoroalkylating reagents. The mild reaction conditions allow access to a wide variety of both aryl-and alkyl-substituted perfluoroalkyl sulfides amenable to pharmaceutical development. Furthermore, the reaction operation is straightforward, odorless, does not produce toxic wastes, and, therefore should appeal to practitioners in industrial-scale productions.

Transition‐Metal‐Free Synthesis of Unsymmetrical Disulfides via Three‐Component Reaction of Thiosulfonates, Thiourea and Alkyl halides

“…Conversely, S‐benzylisothiouronium salt was detected after mixing thiourea and 2 a together, and then the formed salt attacked the electrophilic thiosulfonate 1 a to release the product 3 aa in the presence of K 2 CO 3 (Figure 2, c). These empirical results as well as previously reported literatures [16a,17] support the rationality of our reaction design (Figure 1).…”

Synthesis of Symmetrical Thiosulfonates via Cu(OTf)2‐Catalyzed Reductive Homocoupling of Arenesulfonyl Chlorides

“…Besides, fluorination of thiosulfonate 2 a gave rise to the sulfonyl fluoride 3 c , [12c] which represents the latest and is also one of the most powerful tool for the next generation of click chemistry based on sulfur(VI)‐fluoride exchange (SuFEx) [13] . In addition, the SCF 3 ‐containing product 3 d , a type of important and useful motif widely occurs in numerous pharmaceuticals and other bioactive compounds, [14] could be smoothly got by selective mild‐condition thiotrifluoromethylation [12d] …”

Pentafluoroethylation of Carbonyl Compounds by HFC-125 via the Encapsulation of the K Cation with Glymes

“…The development of the incorporation of the pentafluoroethyl (C 2 F 5 ) group into small molecules has generally followed a similar trend as the trifluoromethyl (CF 3 ) group. For instance, examples using trifluoromethyl trimethylsilane (CF 3 SiMe 3 ) and pentafluoroethyl trialkylsilanes (C 2 F 5 SiR 3 ) have been widely studied, and their use directly as reagents or trapped as cuprate salts has increased, although the trifluoromethyl analogues are much more extended. Pentafluoroethyl iodide (C 2 F 5 I) as a reagent for the radical reaction, or a precursor of organometallic complexes, follows the trialkylsilane-based reagents as the next most used.…”