The Application Of NFSI In The Construction Of Unsymmetrical Disulfides

Unsymmetrical disulfide compounds are very important branch of organic sulfur-containing compounds,which widely exist in various natural product chemistry,medicinal chemistry,food chemistry,chemical biology and materials science.The synthesis methods of unsymmetric disulfide compounds are mainly divided into two categories: one is to synthesize unsymmetric disulfide compounds by constructing S-S bonds,and the other is to synthesize unsymmetric disulfide compounds by constructing C-S bonds.The synthesis of unsymmetric disulfide compounds by constructing S-S bonds mainly includes dehydrocoupling between two thiols,substitution reactions between thiols and thiol derivatives,and exchange reactions between two symmetrical disulfide compounds.In addition,unsymmetric disulfide derivatives can also be synthesized by activation,cleavage,and reorganization of prefunctionalized disulfide C-S bonds.Generally,thiol dehydrocoupling and thiol substitution reactions inevitably use odorous thiols and generate self-coupling by-products.The exchange reaction of S-S bonds and the construction of C-S bonds generally require the use of transition metal catalysts.Therefore,it remains a great challenge to develop green and efficient methods to obtain various unsymmetric disulfides without the involvement of transition metals.N-Fluorobisbenzenesulfonamide(NFSI)is widely used in organic synthesis.NFSI can participate in the fluorination reaction not only as a fluorine source,but also as a "fluorine-free" functionalizing reagent.This paper reports the synthesis of unsymmetric disulfide compounds using NFSI as a catalyst or additive.The main content includes the following three parts:Part Ⅰ: The synthetic methods of several common unsymmetric disulfide compounds and the application of NFSI in organic synthesis are introduced in detail.Part II: We developed a NFSI-catalyzed exchange reaction between symmetric disulfide compounds to construct various important unsymmetric disulfide compounds and their derivatives.This method uses NFSI as a catalyst and two different symmetric disulfide compounds as the starting materials to synthesize a series of unsymmetric disulfides in high yields(up to 90%)in 1,2-dichloroethane(DCE).The method realizes the synthesis of aryl-alkyl,alkyl-alkyl and aryl-aryl unsymmetric disulfide compound substrates without transition metal catalyst.This method has not only been successfully applied to the modification of natural products but also enriched the synthesis of unsymmetric disulfide compounds.Part III: We developed equivalent NFSI to promote the substitution reaction between sulfide compounds and symmetric disulfide compounds to realize the synthesis of unsymmetric disulfide compounds and their derivatives.In this reaction,thioether compounds and symmetrical disulfide compounds are used as reaction raw materials,and under the action of equivalent NFSI,the cleavage of the C-S bond of the thioether compound and the cleavage of the S–S bond of the symmetrical disulfide compound to construct a new S-S bond,and finally realize the synthesis of unsymmetric disulfide compounds.The method successfully realizes the conversion of sulfide compounds into unsymmetric disulfide compounds,which provides a new idea for the synthesis of unsymmetric disulfide compounds.