Study On Trifluoromethylthiolation And Perfluoroalkylthiolation With R_FSO₂Na

Fluorine-containing compounds have been widely used in pharmaceuticals,agrochemicals,dyes,and materials because of their unique biological activity and physicochemical properties.Among fluorous functional groups,the trifluoromethylthio group?SCF3?and perfluoroalkylthio group?SRF?have attracted great attention from both academic and scientific research due to their strong electron-withdrawing,high lipophilicity and stable C-F chemical bond characters.The incorporation of these special segments onto organic molecules often modulate the properties,leading to changes in acidity,dipole moment,polarity,amphipathy,stability and metabolic rate of the organic molecules.Moreover,perfluoroalkylthio group?SRF?moieties with a fluorous chain can stabilize the parent molecules and change their amphiphilic properties.Herein,simple and effective methodologies for the trifluoromethylthiolation and perfluoroalkylthiolation are of high demand.In this paper,direct electrophilic trifluoromethylthiolation of aromatic compounds,as well as indoles has been developed.After screening,?EtO?2P?O?H was an excellent reductant with CF₃SO₂Na in the presence of Lewis acid,which successefully promoted the trifluoromethylthiolation.Moreover,this method has been extended to perfluoroalkylthiolation reactions using RFSO₂Na.The optimal reaction conditions were as follows:using 1.5 equiv of CF3SO₂Na or RFSO₂Na,2.0 equiv of?Et0?2P?O?H,1.5 equiv of FeCl3,in ClCH2CH2Cl at 95?for 24 hours,giving product in good yields?up to 95%yield?.The aromatic compounds with several electron-donating groups have higher yields than that containing electron-withdrawing groups.And electron-donating groups can also enhance the yields of indole compounds.A series of RFSO₂Na compounds such as C₂F₅SO₂Na,C₄F₉SO₂Na,C6F13SO₂Na,C8F17SO₂Na were successfully synthesized,which were employed for perfluoroalkylthiolation reactions on aromatic compounds and indoles.All synthesized compounds were characterized by 1H NMR,13C NMR,19F NMR,and HRMS.