PdCl₂/DMSO-Catalyzed Thiol–Disulfide Exchange: Synthesis of Unsymmetrical Disulfide

Abstract

Unsymmetrical disulfides have been effectively prepared through thiol exchange with symmetrical disulfides employing a simple PdCl 2 /DMSO catalytic system. The given method features excellent functional group tolerance, a broad substrate scope, and operational simplicity. This reaction is especially useful for late-stage functionalization of bioactive scaffolds such as peptides and pharmaceuticals. Disulfidecontaining organic dyes have also been prepared. This transformation could be extended to thiol−diselenide or thiol− ditelluride exchange affording RS−SeR′ or RS−TeR′.

Decatungstate-catalyzed radical disulfuration through direct C-H functionalization for the preparation of unsymmetrical disulfides

“…Considering C-SS bond formation, that approach has benefited from the development of electrophilic and nucleophilic “masked” disulfuration reagents 25 , 26 . These transformations proceed through metal-catalyzed cross-coupling 27 , 28 or substitution reactions 15 , 29 – 31 . It is worth mentioning that in these disulfuration processes, one reaction component carries both sulfur atoms rendering such methods valuable for the preparation of unsymmetrical disulfides.…”

Efficient Synthesis of Symmetrical and Unsymmetrical Disulfides Using a Continuous Flow Method

“…In this context, a series of synthetic methodologies were disclosed in the literature including cross‐coupling reaction of thiols, [5] aerial oxidation with electricity [6] and photo‐organo catalysis, [7,8] of disulfide. In base‐catalyzed reactions, aerobic oxidative hetero‐coupling of thiols has also been described for synthesizing unsymmetrical disulfide using carbonate salts as catalysts [9,10] . Although this system has advantages, it also suffers some drawbacks including the presence of two symmetrical disulfides and the requirement of excess oxidants.…”

“…In base-catalyzed reactions, aerobic oxidative hetero-coupling of thiols has also been described for synthesizing unsymmetrical disulfide using carbonate salts as catalysts. [9,10] Although this system has advantages, it also suffers some drawbacks including the presence of two symmetrical disulfides and the requirement of excess oxidants. Upon visible light irradiation, riboflavin-based catalyst [8] promoted the formation of unsymmetrical disulfide by chemoselective cross-coupling.…”

An (NH4)2S2O8-promoted cross-coupling of thiols/diselenides and sulfoxides for the synthesis of unsymmetrical disulfides/selenosulfides

“…9 An alternative approach to constructing unsymmetrical disulfides involved transition metal-catalyzed disulfide-disulfide 10 or thiol-disulfide exchange reactions (Scheme 1, paths c and d). 11 Recently, various nucleophilic or electrophilic disulfurating reagents have been prepared and applied in the synthesis of unsymmetrical disulfides through metal-catalyzed cross-coupling or substitution reactions (Scheme 1, path e). 12 Despite these advances, some limitations such as the use of unavailable starting materials, the need for noble metals, and complicated manipulations have persisted.…”