Synthesis and Applications of Organosulfur Compounds

Organosulfur compounds encompass a broad class of molecules in which carbon–sulfur bonds confer unique chemical and biological properties. The versatility of sulfur manifests in thiols, disulfides, polysulfides, sulfonamides and related derivatives, each offering distinct reactivity profiles. Synthetic strategies have evolved from classical oxidative couplings of thiols to advanced catalytic methods that enable selective formation of S–S, S–N and S–C bonds under mild, sustainable conditions. Photochemical, nickel-catalysed and copper-mediated protocols permit site-selective functionalisation of aliphatic or aromatic substrates, often in aqueous or solvent-free media. Applications span drug discovery, polymer design, materials chemistry and environmental protection. Disulfide linkages serve as dynamic covalent connectors in responsive materials and bioconjugation, while polysulfides and sulfenamides function as scaffolds in pharmaceutical chemistry. Recent advances emphasise green reaction design, late-stage modification of complex molecules and scalable reagent synthesis, reinforcing the global significance of organosulfur chemistry in both fundamental research and industrial practice.

Research from Nature Portfolio

Recent studies have introduced a decatungstate-catalysed approach for direct C–H functionalisation, enabling the conversion of aliphatic and aldehydic C–H bonds into unsymmetrical disulfides with tetrasulfide reagents under visible-light irradiation. This protocol operates at ambient temperature, employs a readily available photocatalyst and tolerates complex drug-like substrates for late-stage diversification. In parallel, a nickel-catalysed reductive cross-electrophile coupling has been developed to assemble unsymmetrical disulfides from simple alkyl bromides and tetrasulfides. This method utilises inexpensive nickel catalysts to achieve regioselective S–S bond formation without pre-activated sulfur reagents, offering scalability and mechanistic clarity. Complementing these advances, copper-catalysed nitrene-mediated S-amidation provides access to N-acyl sulfenamides from thiols and dioxazolones. The resulting sulfenamides serve as efficient S-sulfenylating agents for the synthesis of sterically demanding disulfides under mild conditions, expanding the toolkit for late-stage modification of bioactive molecules.

Synthesis and Applications of Organosulfur Compounds publication trend

The graph below shows the total number of articles in synthesis and applications of organosulfur compounds across all publications each year (not limited to Nature Index journals).

Technical terms

Thiol: An organosulfur compound containing an –SH functional group, analogous to alcohols.

Disulfide: A compound featuring an –S–S– linkage, often used in reversible covalent chemistry.

Polysulfide: A molecule containing chains of sulfur atoms (–Sₙ–), where n > 2, with applications in materials and biology.

Sulfenamide: An organosulfur species bearing an S–N bond, useful as a masked sulfenylating reagent.

Photocatalysis: Activation of chemical transformations by light in the presence of a catalyst, enabling mild and selective reactions.

References

1. Decatungstate-catalyzed radical disulfuration through direct C-H functionalization for the preparation of unsymmetrical disulfides. Nature Communications (2022).
2. Efficient preparation of unsymmetrical disulfides by nickel-catalyzed reductive coupling strategy. Nature Communications (2022).
3. Synthesis of N-acyl sulfenamides via copper catalysis and their use as S-sulfenylating reagents of thiols. Nature Communications (2022).
4. Visible Light‐Driven Photocatalytic Transformation of Thiols to Disulfides in Water Catalyzed by Bi2S3. Advanced Energy and Sustainability Research (2023).
5. Facile Synthesis of Sulfonyl Chlorides/Bromides from Sulfonyl Hydrazides. Molecules (2021).
6. Application of Bulky NHC–Rhodium Complexes in Efficient S–Si and S–S Bond Forming Reactions. Inorganic Chemistry (2021).