Electrophilic Thiolation Reaction Based On Benzenethiosulfonate

Organosulfur compounds,especially thioethers and sulfones,are a kind of plentiful and important organic compounds,which widely present in a variety of amino acids,proteins,vitamins,antibiotics and other natural products.They play a decisive role in the metabolism of human,other animals,plants,and maintenance of vital activity.Due to its special properties,organosulfur has been widely used in polymer materials,organic chemistry,pharmaceutical,pesticide and other fields.According to statistics,about one fifth of new drugs contain sulfur element,so the synthesis of organic sulfur compounds and the construction of C-S bond is of great significance to organic chemistry,material chemistry and pharmaceutical chemistry.The traditional C-S formation reaction is usually the nucleophilic substitution reaction of the nucleophilic stink RSH to the C?+ compound.This kind of coupling substrate is limited to the substances with leaving group,such as halogenated hydrocarbon,trifluoromethylsulfonate,etc.In this paper,four new reactions for the construction of C-S bonds have been developed about electrophilic thiolation:(1)Scandium-catalyzed highly selective atom transfer addition of electrophilic thiolation reagent ArSO2SR to aromatic/aliphatic olefins.Sc(OTf)3 is used for the first time in the reaction of olefin sulfonation and thiolation/selenization.The olefins undergo sulfonation and thiolation in one-step to form two C-S bonds,and achieve 100%atomic economy.The starting materials are cheap and easy to prepare with a wide range of substrates.Compared with the previous olefin disulfide reactions,the regioselectivity of thiosulfonylation has achieved complete inversion and the cycloene has achieved highly efficient trans-addition.The reaction undergoes Lewis acid assisted ionic reaction mode.(2)The first copper-catalyzed trifunctionalization of alkenes to synthesize functionalied ?-keto thiosulfones through radical addition.Under mild conditions,CuTc catalyzes the formation of benzenesulfonyl radicals without other oxidants.The benzenesulfonyl radical and olefin undergo the relay process of radical addition/oxygen oxidation/thiolation in the air.We can construct two C-S bonds and one C=O double bond in single operation to achieve the tandem sulfonation/oxidative/thiolation reaction of olefins.The whole process is green and efficient,which provides a simple path for the synthesis of ?-thioketone bioactive compounds.(3)Novel trifluoroethylthiobenzene sulfonate reagent PhSO2SCH2CF3:an electrophilic trifluoroethylthiolation of ?-ketoester.Fluoroalkylthiolation is an important reaction in pharmaceutical industry.We use trifluoroethylamine hydrochloride and tert-butyl nitrite to generate trifluoroethyldiazo compounds in situ,which react with PhSO2SNa to synthesize a new type of PhSO2SCH2CF3 reagent for the first time under mild conditions.This reagent can react with a variety of ?-ketoester to achieve electrophilic trifluoroethylthiolation through metal-free approach.(4)Copper-catalyzed interrupted Click reaction/tandem thiolation process:one-pot synthesis of sulfur heterocycle fused 1,2,3-triazoles.Through the mechanism study,we think that cuprate-triazole formed in situ by CuAAC reaction of the alkynes and azides compounds,which is intramolecular intercepted by the benzenethiosulfonate.Five-/six-/seven-sulfur hetercycle fused 1,2,3-triazoles were synthesized through electrophilic thiolation.The substrate is widely applicable to many alkynes derived from amino acids,glucose,vitamin E,estrone and other natural products.