Design And Application Of Disulfurating Reagents

Disulfide is a significant functional molecule,which presents broad range of application in chemical biology,pharmaceutical industry and food chemistry.Therefore,development of highly efficient synthetic methods to access sulfur-sulfur bond has been intensively pursued by synthetic community.Symmetrical disulfide can be facilely synthesized via oxidation of thiol,while efficient synthesis for unsymmetrical disulfide have been scarcely reported.Oxidative cross coupling between two different odorous thiols is an alternative pathway,in which homo-coupling products and byproducts of other oxidation state are unavoidable.The exchanging protocol between two distinct symmetrical disulfides to construct unsymmetrical disulfide need to employ nobel metal catalyst.Furthermore,SN2 replacement is a typical method for disulfide construction utilizing prefunctionalization of two thiols,which is carried out under harsh conditions.Therefore,it's urgent to develop the efficient and environmentally friendly disulfurating reagent.During my doctorate reseaches,I focused on designing and developing new disurating regent and appling it to constructing unsymmetrical disulfide.Part one:Using inorganic sulfur sources to synthsize unsymmetrical disulfide via comproportionation.Various kinds of unsymmetric disulfides were constructed efficiently by comproportionation between sulfinates and thiosulfates,which are characterized by odorlessness,economy and practicability.Neither extra oxidant nor reductant was needed in this transition-metal-free reaction,which made this chemistry environmentally friendly and practical.Many functional group can be compatible in the reaction.What's more,methyl disulfide and other significnt disulfide can be afforded smoothly.The key intermediates were isolated and series of control experiments revealed an outline of mechanism of comproportionation.Part two:Design and application of nucleophilic disulfurating reagent.The designed nucleophilic disulfurating reagent has been establishment facilely,which can be utilized to achieve disulfurating strategy via the direct construction of"di-sulfur".The strategy was realized through copper catalyzed oxdative cross coupling with substrates of arylboronic acid and silane.The selective cleavage of C-S bond was achieved by controlling rate of alcoholization under mild conditins.Diverse substrates and biomolecules are well compatible for unsymmetrical disulfide formation through introducing "di-sulfur" in one step.Mask and base effect revealed alcoholysis rate using sodium carbonate matched transmetalation rate perfectly was the key factor of disulfuration.Part three:Design and application of electrophilic disulfurating reagent.The electrophilic disulfurating reagent has been designed and synthsized by umpolung strategy,which can be accomplished gram-scale operation with millimol of catalyst loading.Numerous kinds of nucleophile can be utilized to construct the corresponding disulfide,such as indole,electron-rich arene,dicarbonyl substrate,amine.Significantly,the polysulfides can be constructed by this methodology.The unsymmetrical disulfide and polysulfide has been afforded efficiently without transition metal and base under this mild reaction system.