Study On The Synthetic Methods Of Sulfur-containing Compounds From Sulfinic Acid Derivatives

Sulfinic acid derivatives are stable,odorless and easy-to-handle sulfur-containing precursor compounds,and thus are desirable sulfur sources for the synthesis of sulfur-containing compounds.In recent years,considering the importance of sulfur-containing compounds in the field of chemistry,biology and pharmaceutical sciences,sulfinic acid derivatives have been paid more attention,and have been widely used in the synthesis of sulfur-containing compounds such as sulfoxides,sulfones,sulfinates and thioethers.In recent years,with the development of the concept of green and sustainable chemistry,how to design a more efficient and milder reaction for the synthesis of target compounds has become a research hotspot in the field of organic synthesis chemistry,which has been widely concerned by researchers.The main topic of this paper is the synthesis and mechanism exploration of sulfinates,sulfoxides and thioethers from sulfinic acid derivatives,which could provide a novel,mild,efficient and promising approach for the synthesis of sulfur-containing natural products.The detail works are described as follows:An efficient sulfination reaction of alcohols with sodium arylsulfinates is described.With the use of TMSCl as the promoter,the reaction went smoothly under metal-free and mild conditions.Various alcohols with sodium arylsulfinates are converted into the corresponding sulfinates in moderate to excellent yields（up to 95%）.¹⁸O-isotope labeling experimental results shows that one oxygen atom of an alcohol acts as the nucleophilic attacking atom in the reaction process.Furthermore,the revised reaction mechanism has been applied to sulfinylation of electron-rich aromatics with sodium arylsulfinates by using TMSOTf as a promoter.Various sulfoxides were obtained in excellent yields（up to 95%）.An efficient sulfinylation reaction of indoles and pyrroles with sulfinamides is developed.The sulfinylation of indoles and pyrroles with sulfinamides using this protocol is oxidant-free and under obviously more feasible conditions（1.2 equiv.of indoles or pyrroles,10 min）in comparison to the precedent procedure（3–20 equiv.of indoles or pyrroles,16–18 h,ammonium persulfate as oxidant,hv）.A variety of functional groups were tolerated,and various C3-thioindoles and C2/3-thiopyrroles were obtained in moderate to excellent yields（up to 94%）.Most importantly,a highly selective C3-or C2-sulfinylation of pyrroles with sulfinamides has been accomplished by controlling the reaction time.A switchable regioselectivity in C–H thiolation reaction by simply swapping the counteranions of TMS is reported here.An exclusive C3–H thiolation of indoles with sodium arylsulfinates was achieved in the presence of TMSCl as promoter.In contrast,with the use of TMSOTf instead of TMSCl under otherwise identical conditions,a regiospecific C2–H thiolation of indoles was realized with the same set of substrates.The reaction went smoothly under metal-free and mild conditions and various indoles with sodium arylsulfinates are converted into the corresponding C3-and C2-thioindoles in moderate to excellent yields（up to 96%）.Experimental evidences were provided to support a mechanism involving a sequence of Friedel–Crafts acylation,interrupted Pummerer reaction and 1,2-migration rearrangement.Indoles appeared to serve the dual role of the substrates and reduction agents in these reactions.In the exploring process of the C–H thiolation reaction mechanis,byproduct chlorinated indoles were also studied,and an efficient chlorination of indoles with chlorine anion as nucleophile is described.With the use of ethyl phenyl sulfoxide as the promoter,the reaction went smoothly under metal-free and mild conditions.A plausible interrupted Pummerer reaction mechanism was proposed without the oxidation of chloride anion.Various indoles are converted into the corresponding chlorinated compounds in moderate to excellent yields（up to 95%）.