Construction Of Unsymmetrical Disulfanes And Synthesis And Application Of Novel Disulfide Reagents

Unsymmetrical disulfides are a class of organic sulfur compounds with a disulfide bond(-S-S-)structure and different functional groups attached to the sulfur atoms on both sides of the disulfide bond.They are widely found in natural products,food chemistry,biological molecules,pharmaceutical chemistry,and other fields,which have attracted much attention due to their unique physicochemical and pharmacological properties.Currently,there are two strategies for synthesizing unsymmetrical disulfides: one is to synthesize them by constructing S-S bonds,and the other is to synthesize them by constructing C-S bonds.Traditional methods for synthesizing unsymmetrical disulfides by constructing S-S bonds include oxidative coupling,nucleophilic substitution,and disulfide exchange reactions.However,self-coupling by-products and over-oxidation are inevitably present in these methods.To avoid these circumstances,the rapid development of synthesizing unsymmetrical disulfides has been achieved through reacti ons such as nucleophilic substitution and cross-coupling to construct C-S bonds with the aid of disulfide reagents.In recent years,the effective construction of unsymmetrical disulfides through free radical chemistry under mild conditions has attracted widespread attention,providing a new approach for the efficient synthesis of unsymmetrical disulfides.Additionally,designing and synthesizing novel disulfide reagents and exploring new disulfide reactions have also provided new methods for synthesizing unsymmetrical disulfides.Based on these developments,this paper combines free radical chemistry to develop methods for synthesizing unsymmetrical disulfides and designs and synthesizes novel disulfide reagents for preparing these compounds.The main research content is summarized as follows:1)A Co(salen)-catalyzed hydrogenation-disulfidation reaction of non-activated alkenes was developed,using p-toluenesulfonyl disulfide reagent.Unique Markovnikov selectivity products were observed in all cases.This reaction has wide functional group compatibility and provides a practical tool for lat e-stage modification of natural products and drug molecules.2)A visible-light-promoted heteroaryl migration disulfide sulfenylation reaction was developed,using butenyl heteroaryl sulfoxide and arylsulfonyl disulfide reagent to synthesize polysulfides.The reaction undergoes a free radical addition/Smiles rearrangement/free radical substitution process under metal-free conditions,and has the advantages of mild conditions,wide substrate scope,high atom economy,and efficient one-step formation of three chemical bonds.A series of control experiments demonstrated that arylsulfonyl disulfide reagents are both arylsulfonyl radical precursors and sources of tetrasulfur compounds that react with alkyl radicals.Additionally,the heteroaryl migration disulfid e sulfenylation product can be converted into valuable dihydrothiophene and highly conjugated disulfides under alkaline conditions,further increasing the value of this method.3)Two free radical disulfide reactions were developed starting from allylic sulfides.One is a free radical directed substitution disulfidation reaction of alkyl allyl sulfoxides with p-toluenesulfonyl disulfide reagent initiated by a free radical initiator.The other is a free radical substitution reaction of alkyl amine-derived N-allyl sulfonamides with p-toluenesulfonyl disulfide reagent,achieving remote site-specific peroxidation on non-activated alkyl C-H bonds and constructing a series of 5-or 6-alkyl disulfide amide derivatives.4)A new type of peroxide amine disulfide reagent was designed and synthesized,which is simple to prepare without requiring anhydrous or oxygen-free conditions.The structure of the reagent is controllable,and the electrostatics and steric hindrance of the reagent can be changed by regulating the su bstituent on the nitrogen atom.The reagent can be prepared on a large scale,which is advantageous for later-stage transformations.In addition,the transformation of this new peroxide amine disulfide reagent was studied.The reagent can be directly and e fficiently applied to nickelcatalyzed cross-coupling reactions to synthesize aryl alkyl unsymmetrical disulfides.Additionally,the reagent can be used in nickel-catalyzed three-component coupling reactions to achieve 1,2-arylation disulfidation reactions of non-activated alkenes.