Reaction Of Azodicarboxylates With Sulfur-containing Unsaturated Double Bonds

Azodicarboxylates have strong electrophilicity due to theirs electron-withdrawing ester groups,and nucleophilicty because of the lone pair electrons of nitrogen atoms,so they have been widely used as functional reagents in organic synthesis,especially as Huisgen zwitterion's precursors.From early Mitsunobu reaction,which builds a carbon-heteroatom bond mildly and diversely,to the situation that Huisgen zwitterions can be used as nitrogen sources reacted with a series of electrophilic carbon-carbon double bonds,carbon-nitrogen double bonds,and carbon-oxygen double bonds,constructing nitrogen heterocyclic rings.This kind of compounds exhibit various reactivities and wide applications.However,the reaction of azodicarboxylates with unsaturated double bonds containing sulfur atom still remains underdeveloped.In this dissertation,reactions of azodicarboxylates with three sulfur-containing unsaturated double bond compounds were carried out.The main contents and conclusions are as following:(1)Based on[2+2]annulation of azodicarboxylates with ketenes and[2+2]/[2+2+2]annulation of sulfenes with unsaturated double bond compounds.Reaction of azodicarboxylates with sulfenes which generated in situ from sulfonyl chlorides with ?-hydrogen under basic conditions has been studied.Different from the above annulation reactions,the annulation products were not obtained as a result of the large steric hindrance of the sulfonyl group and low energy of nitrogen-nitrogen bond,a-chloroalkanesulfonyl hydrazines were obtained.A mechanism was proposed that Huisgen zwitterions nucleophilically added to sulfenes followed by substitution of a chloride ion,leaving nucleophile to participate in the catalytic cycle.This reaction provides a novel method to synthesize ?-chloroalkanesulfonyl hydrazines via sulfene intermediates without adding any other chloride sources by one-step,avoiding the drawbacks of chlorination with chlorine and reducing the reaction steps compared with traditional methods.It also extends the reaction system of sulfenes and compounds with unsaturated double bonds(aldehydes,ketones,imines,and electron-rich olefins).(2)Synthesis of sulfonyl hydrazine compounds from thiols and azodicarboxylates followed by oxidation was realized.This is a novel preparation method for sulfonyl hydrazines with advantages of a wide range of substrates,good functional group tolerance,and high yields.Addition reaction of thiols to azodicarboxylates gave sulfinyl hydrazines and the following oxidation reaction with m-CPBA completed the conversion of sulfinyl hydrazine compounds to sulfonyl hydrazine compounds efficiently.A series of alkyl,aryl,and pyridyl sulfonyl hydrazines were achieved,the case of gram-scale reaction was also available.In addition,the addition reaction of thiols to azodicarboxylates also reflected the nucleophilic abilities of various thiol compounds,which provided a reference for future design on their nucleophilic additions.(3)Reaction of azodicarboxylates with sulfur ylides as sulfur-containing unsaturated double bond compounds instead of sulfenes was investigated.A new method for the preparation of hydrazones and hexahydrotetrazine-1,2,4,5-tetracarboxylates without additives or metal-catalysts was developed.The major products of the reaction were effectively controlled by changing reaction temperature.Tetrazine compounds acted as the major products at room temperature,while hydrazone compounds can be obtained only under high temperature conditions.Tetrazine compounds decomposed into more stable hydrazones due to their instability,indicating that heating is the major factor to promote the decomposition of tetrazine compounds.Reactions of sulfur ylides with azodicarboxylates catalyzed by metal catalysts were also carried out with the same results.In terms of mechanism,the additive-free method utilizes the nucleophilicity of sulfur ylides to complete the reaction by ion pairing mechanism.Under the metal catalytic conditions,the product were obtained through the metal carbene intermediates which proved by the carbene dimerization by-products.These two reaction mechanisms reflected the electrophilicity and nucleophilicity of azodicarboxylates,respectively,revealing the diverse reactivities of such compounds.(4)Reaction of azodicarboxylates with 1,2,3-thiadiazoles as carbene precursors was explored,giving no satisfied results.Rhodium-catalyzed[3+3]annulation reaction of thioacylcarbenes generated from 1,2,3-thiadiazoles with 2-alky-2-ynals was achieved when using alk-2-ynals instead of azodicarboxylates.The reaction has good functional group tolerance,phenylpropynyl aldehydes containing electron-withdrawing,electron-donating group,alkyl,and heterocyclic 2-ynals can complete the reaction,realizing effective synthesis of a series of monoaryl monoalkyl,diaryl,and dialkyl 4H-thiopyran-4-ones.Derivatization of the products was carried out,affording the molecules that acted as a functional material.It was proposed that the oxidative addition of alky-2-ynals gave the acyl hydrides as the key intermediates of the reaction,followed by the reaction mechanism of the l,1-hydroacylation of the thioacylearbenes formed from thiadiazoles.The kinetic isotope effect revealed that the oxidative addition step is the rate-determining step of the reaction,and structural modifications of the natural product estrone were also achieved by this method.