Synthetic Applications of Sulfonium Salts in Organic Chemistry

Sulfonium salts, characterised by a trivalent, positively charged sulfur centre attached to three organic substituents, have emerged as versatile reagents in modern synthesis. Their intrinsic thermal stability, tolerance to air and moisture and ease of purification confer practical advantages over many hypervalent iodine analogues. During the past decade, protocols for direct preparation of diverse aryl- and alkyl-sulfonium species on multigram scale have flourished, enabling chemists to exploit these reagents in cross-coupling, C–H activation and radical-mediated bond construction. Advances in photocatalysis and electron donor–acceptor (EDA) complex formation have unlocked new modes of activation under mild, often metal-free conditions.

Key synthetic applications include site-selective C–H thianthrenation to install a sulfonium handle on arenes or alkenes, which can then undergo downstream substitution to forge C–C, C–N, C–O, C–S and C–B bonds with high chemo- and regioselectivity. Parallel developments in photoredox catalysis have harnessed sulfonium salts as precursors to carbon-centred radicals, facilitating radical cross-coupling and late-stage functionalisation of complex molecules. In this context, sulfonium reagents serve as bench-stable surrogates for radical initiators, broadening access to scaffolds of pharmaceutical and materials interest.

Beyond classical polar mechanisms, the formation of EDA complexes between sulfonium acceptors and suitable donors allows visible-light-driven halogen-atom transfer and divergent bond-forming processes. The union of sulfonium chemistry with electrochemical and transition-metal catalysis has further expanded the repertoire of transformations, offering catalytic alternatives to stoichiometric reagents. Collectively, these innovations underscore the global significance of sulfonium salts as sustainable, operationally simple tools for complex molecule assembly and diversify retrosynthetic disconnections previously limited by functional-group sensitivity.

Research from Nature Portfolio

Recent studies have introduced a unified, metal-free protocol for intermolecular Heck-type functionalisation of alkenes via thianthrenation. Under operationally simple conditions at room temperature, cine-selective C–H activation of both aliphatic and aryl alkenes is achieved, enabling C–C, C–N, C–P and C–S bond formation with a range of nucleophiles including sulfinates, cyanides, amines and amides.

Another breakthrough has been the generation of non-stabilised alkyl radicals from S-(alkyl) thianthrenium salts under photoredox conditions. This method delivers controlled C–B bond formation to generate alkylboronates, as well as heteroarylation, alkylation, alkenylation and alkynylation processes. The practical procedure converts C–OH precursors into C–B and C–C bonds, offering a versatile platform for late-stage diversification.

Synthetic Applications of Sulfonium Salts in Organic Chemistry publication trend

The graph below shows the total number of articles in synthetic applications of sulfonium salts in organic chemistry across all publications each year (not limited to Nature Index journals).

Technical terms

Sulfonium salt: Organic compound featuring a positively charged trivalent sulfur atom bonded to three organic groups.

Thianthrenation: Introduction of a thianthrene-derived sulfonium moiety onto an organic substrate to enable subsequent functionalisation.

Electron donor–acceptor (EDA) complex: Non-covalent association between an electron-rich donor and an electron-deficient acceptor that undergoes photoinduced electron transfer.

Photoredox catalysis: Activation of substrates via light-driven single-electron transfer mediated by a photocatalyst.

Site-selective C–H functionalisation: Targeted modification of a specific C–H bond in the presence of multiple, chemically similar C–H bonds.

References

1. Dibenzothiophenium Salts: Practical Alternatives to Hypervalent I(III)-Based Reagents. Accounts of Chemical Research (2025).
2. Unified metal-free intermolecular Heck-type sulfonylation, cyanation, amination, amidation of alkenes by thianthrenation. Nature Communications (2024).
3. Generation of non-stabilized alkyl radicals from thianthrenium salts for C–B and C–C bond formation. Nature Communications (2021).
4. Aryl sulfonium salt electron donor-acceptor complexes for halogen atom transfer: Isocyanides as tunable coupling partners. Chem (2024).
5. Stabilized Carbon Radical‐Mediated Assembly of Arylthianthrenium Salts, Alkenes and Amino Acid/Peptide Derivatives. Advanced Science (2024).
6. Photoinduced Copper-Catalyzed Late-Stage Azidoarylation of Alkenes via Arylthianthrenium Salts. Journal of the American Chemical Society (2023).
7. Radical C−C Bond Formation using Sulfonium Salts and Light. Advanced Synthesis & Catalysis (2020).