An Overview of Recent Advances in the Synthesis of Organic Unsymmetrical Disulfides

Abstract

Organic unsymmetrical disulfides have been extensively applied in various academic and industrial fields including intermediates in organic synthesis, agriculture, and food science, natural materials, biochemistry, pharmaceutical and medicine chemistry, polymers, material engineering, etc. They play a crucial role in the fabrication of various biological active sulfur heterocycles. Due to broad and extensive applications, many methods have been developed for the synthesis of unsymmetrical S−S and efforts have been made to improve some issues such as cost, energy efficiency, green chemistry, avoid or minimizing waste generation. Several outstanding review articles have been previously published highlighting the advances of S−S bond formation, in general, using various reagents under different conditions in the absence or presence of oxidants/catalysts. In 2020, a review paper was published by our group focusing on recent developments since 2014 in the synthesis of organic symmetrical disulfides. However, investigations on new catalytic methods are being regularly reported and new types of unsymmetrical disulfides are synthesized. The present overview has attempted to systematically summarize recent advances in the process of unsymmetrical S−S bond formation with a major focus since 2010, highlighting mechanistic considerations, substrate scope, advantages, and limitations. The patents are not studied in this overview.

N‐Iodosuccinimide (NIS) Promoted Synthesis of Unsymmetrical Disulfides Starting from Isothiocyanates Under Transition‐Metal‐Free Conditions

“…Based on the control experiments and related literatures, [10,14d,20] we proposed a possible mechanism for this reaction (Scheme 3). Initially, compound 1 a reacted with CH 3 OH under the action of base to form A , and A was isomerized into B in the presence of base.…”

“…Due to the important role of disulfides in various fields, the synthesis of disulfides has attracted the interest of many chemists [10,11] . Though a couple of ways to synthesize symmetrical disulfides have been developed previously, the synthesis of unsymmetrical disulfides is comparatively undeveloped.…”

“…[9] Due to the important role of disulfides in various fields, the synthesis of disulfides has attracted the interest of many chemists. [10,11] Though a couple of ways to synthesize symmetrical disulfides have been developed previously, the synthesis of unsymmetrical disulfides is comparatively undeveloped. Among these various strategies (Scheme 1), the most traditional and common method to give unsymmetrical disulfides is the construction of SÀ S bonds by cross-coupling between different thiols.…”

Photocatalytic C–H Disulfuration for the Preparation of Indolizine-3-disulfides

“…In recent decades, chemists have worked on designing and synthesizing various asymmetric disulfides. However, most of the literature reported that the reaction was carried out using thiol as a substrate, with a bad smell and low commercial value . Thus, considerable efforts had been spent to develop alternative reagents as S-S sources to synthesize disulfides, for example, RSSSSR, RSSLG, NuSSNu, RSSAc, and RSSTs (Scheme b).…”

Practical synthesis of unsymmetrical disulfides promoted by bromodimethylsulfonium bromide

“…In this context, the main challenge is avoiding the generation of significant amounts of symmetrical by-products. Therefore, known procedures generally employ two thiols with obvious difference in the abilities to be oxidized, 22–28 or pre-converting one thiol to stable electrophilic agents, such as sulfenamides, 29,30 thiosulfonates 31 and organophosphorus sulfenyl derivatives. 32,33 Sulfenyl chloride intermediates have been investigated in situ and used for asymmetrical disulfides synthesis.…”