Disulfide Compounds Mediated Functionalization Of Aromatic/Heterocycle

Disulfide compounds mediated functionalization of aromatic/heterocycle has attracted widespread attention.In recent years,the interrupted-Pummerer reactions of sulfoxide and other sulfinic acid derivatives such as sulfinamides and sulfinate esters have been wildly explored.In this thesis,two types of disulfides compounds,thiosulfinates and disulfides,were investigated as a novel thiolation reagent for the functionalization of aromatic/heterocycle.The interrupted-Pummerer reaction of activated thiosulfinate and the cross-dehydrogenative coupling reaction between disulfides and purine have been developed.In the first chapter,the properties,preparation methods and applications in synthesis of thiosulfinates and disulfides were introduced.The interrupted-Pummerer reactions of sulfoxide and other sulfinic acid derivatives were summarized.Under the activation of electrophiles,sulfinic acid derivatives became a strong electrophilic,which could conduct electrophilic attack on aromatic rings,nitrogen heterocycles and alkenes and could be connected with various reactions.The cross-dehydrogenative coupling reactions of thioether or ether were introduced.After the ortho-position hydrogen of sulfur and oxygen atom was activated,it could realize functionalization of aromatic/heterocyclic compounds.In the second chapter,the interrupted-Pummerer reaction of thiosulfinate was studied.Based on Pummerer-type conditions,functionalization reaction of indole has been achieved with thiosulfinate.The activated thiosulfinate had strong electrophilic ability and could undergo secondary electrophilic substitution with thiolation products,hence dithio-products were mainly obtained.Even indoles with EWG afforeded dithioindoles.Indoles with EDG gave tri-thioindoles.The monothiolation product could not be selectively obtained with optimized conditions.In the mechanism study,control experiments proved that the intermediate was activated thiosulfinate,ruling out the previous view that mixed acid anhydrides were used as electrophiles.Dithio-products were obtained by secondary substitution of monothio products.The process of secondary substitution proceeds in two ways:three-membered ring rearrangement and direct substitution.This reaction provides a novel method functionalization of indole.In the third chapter,a method for synthesizing alkyl aryl sulfide and diaryl sulfide by interrupted-Pummerer reaction of activated thiosulfinate was developed,which was another application of thiosulfinate.Activated thiosulfinate acted as an electrophilic reagent to conducted electrophilic attack on electron-rich benzene ring,naphthalene ring and phenol to achieve direct C-H functionalization.The selectivity of the reaction was determined by the substituents of the thiosulfinate.Thiosulfinates with EWG afforded dithio-products.For unstable aryl thiosulfinates,a one-pot synthesis method from disulfide was developed.In particular,when the bulky isopropyl,tert-butyl thiosulfinates participated in the reaction,a chlorination reaction was observed,which was used as a new chlorination method after optimization.Mechanistic studies applied that activated thiosulfinate was the main electrophile in the thiolation reaction,while sulfenyl chloride was the main electrophile in the chlorination reaction.In the fourth chapter,the cross-dehydrogenative coupling reaction between purine and C(sp~3)-H of disulfide was developed.Symmetric disulfide was successfully constructed from asymmetric disulfide in this procedure.Disulfide was used as solvent in this reaction,so that the fragile disulfide bond was maintained,and the role of disulfide in this type of reaction was successfully reversed.It was found that the reactivity of methylene hydrogen was better than that of methyl hydrogen,while the allylic and benzylic hydrogens failed to undergo this reaction.The formation and decomposition of thiosulfinate were found in the reaction,whereas control experiments showed that it did not participate in this proccdure.The reaction of asymmetric disulfides was investigated and four crossed products were obtained.Mechanistic studies showed that there was a sulfur exchange reaction in the reaction.In conclusion,novel reactions with activated thiosulfinates as thiolation reagent were developed in this thesis,to achieve bis-alkane thiolation of indole,alkane/aryl thiolation and chlorination of electron-rich aromatic rings.At the same time,the cross-dehydrogenative coupling reaction of purine and disulfide was explored.These new reactions provide powerful tools for the synthesis of complex thioproducts.