Research On The C-S Bond Construction Based On Organic Thiosulfate

Sulfur-containing compounds have important application value in the fields of synthesis,medicine and materials.Although employing thiols and their derivatives to synthesize organic sulfur compounds via transition-metal-catalyzed coupling reaction is very useful,these reactions still have obvious shortcomings and deficiencies.Therefore,we need to find an odorless,inexpensive,easily available,stable and efficient sulfur source to replace thiols and their derivatives to safely and efficiently synthesize organic sulfur-containing compounds.In this paper,the odorless,stable,cheap and easy-to-obtain Bunte salt(organic sodium thiosulfate)is used as a sulfur source to study its application in the construction of C-S bonds.On this basis,combined with the fluorine chemistry,the synthesis method of fluorine-containing organic sulfur compounds was studied.In addition,based on the Bunte salt synthesis route,the synthesis and application of Bunte salt disulfide reagents were further studied.Firstly,the copper-catalyzed decarboxylative cross-coupling reaction of alkynyl carboxylic acids with Bunte salt was studied.was studied.Mechanism studies show that the copper-silver bimetallic catalytic system can activate the corresponding alkynyl carboxylic acids,through decarboxylating to form an active metal-alkynyl intermediate,and then react with different Bunte salts under optimized conditions with the releasing of sulfur trioxide.Finally the reductive elimination of intermediate gives the corresponding alkyne-sulfur compounds.Under the same system,the selenium Bunte salt can also react with acetylenic acid,and the yield of the target product obtained can reach 87%.Then the application of one type of the Bunte salts,sodium methyl thiosulfate,was also studied in the methionylation reaction.This Bunte salt can react with various compounds,such as alkynes,β-dicarbonyl compounds,benzaldehydes,thiols,phosphorous oxygen compounds and amines to obtain corresponding thiomethylated products.The advantages,such as high efficiency,widely substrate scope,and avoid of thiols and their derivatives demonstrate the potential of this reagent.Secondly,combining the characteristics of fluorine chemistry,a new synthetic route of fluorine-containing Bunte salt,sodium S-(fluoromethyl)sulfurothioate was described.And a reaction that employed this reagent as a monofluoromethylthiolation reagent was also developed.Sodium S-(fluoromethyl)sulfurothioate be efficiently synthesized through mild reaction conditions and simple operation from monofluoromethyl iodide and sodium thiosulfate.Under the catalysis of copper,the diazonium salt generated in situ by the aromatic amine can react with this reagent through the steps of oxidative addition,ligand exchange and reduction elimination to remove the amino group and introduce a monofluoromethylthio group to generate the corresponding monofluoromethylthiolating product.Among them,the drug molecule,mosapride can obtain a product modified with a fluoromethylthio group with a yield of 44%.In addition,thiols could also react with this reagent to obtain an unsymmetric disulfide compound containing a fluoromethyl group.The reaction is simple and no catalyst is required.Finally,the synthetic route of the new disulfide reagent based on the structure of Bunte salt and its application as a direct disulfide reagent are described.The disulfide Bunte salt,S-substituted sulphenylthiosulphates can be synthesized from cheap and available sodium thiosulfate and sulfenyl chloride,which was generated in situ from sulfonyl chloride and triphenylphosphine or thiol and N-chlorosuccinimide.There are two competitive procducts in this reaction.After screening conditions,it is found that the addition of acid can control the selectivity of these two products,due to stability of the intermediate.In the presence of acetic acid,3-isopropyldisulfide substituted indole was obtained with 91/9 selectivity and 71% yield.By changing different solvents,a variety of S-aryl and S-alkyl sulphenylthiosulphates and indoles can be applied.The use of transition metal catalysts is avoided.