Sulfone Synthesis and Functionalization Techniques

Sulfones, characterised by a divalent sulphur atom doubly bonded to oxygen and linked to two carbon centres, are indispensable scaffolds in pharmaceuticals, agrochemicals and advanced materials. Traditional access involves oxidation of thioethers or direct sulfonylation of organometallic reagents, yet these often require harsh oxidants or stoichiometric metal waste. Recent developments embrace metal-free dehydrative cross-coupling, photochemical activation and radical-mediated routes to install sulfonyl motifs under mild, green conditions. Transition-metal catalysis remains a powerful tool for C–S bond formation and late-stage diversification, with emerging protocols exploiting earth-abundant copper, manganese or organic photocatalysts. Biocatalytic cascades further extend functional group tolerance, enabling stereoselective assemblies of β-hydroxy sulfones in aqueous media. Collectively, these advances deliver versatile entry points for structural elaboration, unify radical and ionic paradigms and underscore the global push towards sustainable sulfone chemistry.

Research from Nature Portfolio

Metal-free dehydrative cross-coupling of sulfinic acids with allylic alcohols has been shown to furnish allylic sulfones in high yield and selectivity under ambient aqueous conditions. The protocol proceeds at room temperature without transition-metal catalysts and affords products by simple filtration, with mechanistic studies implicating water-mediated hydrogen-bond networks in the activation of substrates.

A dual radical addition/coupling strategy employing sulfinyl sulfones as precursors has unlocked the long-elusive reactivity of sulfinyl radicals. Sequential generation of sulfonyl and sulfinyl radicals enables the one-step construction of linear and cyclic disulfurised adducts from unsaturated hydrocarbons. Experimental and computational investigations illuminate a cascade of radical additions that broadens the scope of C–S bond disconnections.

Sulfone Synthesis and Functionalization Techniques publication trend

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

Technical terms

Sulfones: Organic compounds featuring a sulphur atom doubly bonded to two oxygens and bonded to two carbon centres, valued for stability and polarity.

Sulfinyl radicals: Reactive S-centred species with an unpaired electron on sulphur, capable of rapid addition to unsaturated substrates.

Dehydrative cross-coupling: Bond-forming reaction that joins two entities with concomitant removal of water, often under mild, metal-free conditions.

Oxosulfonylation: Process where a sulfonyl group and an oxygen atom are simultaneously introduced across a multiple bond or functional group.

Chemoenzymatic cascade: Sequential combination of chemical and enzymatic steps in one pot, avoiding isolation of intermediates and enhancing stereocontrol.

Photochemical activation: Use of light energy to promote bond formation via radical or ionic pathways, enabling milder and more selective transformations.

References

1. Water-promoted C-S bond formation reactions. Nature Communications (2018).
2. Synthetic exploration of sulfinyl radicals using sulfinyl sulfones. Nature Communications (2021).
3. Iodine-mediated photoinduced tuneable disulfonylation and sulfinylsulfonylation of alkynes with sodium arylsulfinates. Chemical Communications (2023).
4. Chemoenzymatic Oxosulfonylation‐Bioreduction Sequence for the Stereoselective Synthesis of β‐Hydroxy Sulfones. ChemSusChem (2021).
5. Copper catalysed oxidative α-sulfonylation of branched aldehydes using the acid enhanced reactivity of manganese( iv ) oxide. Chemical Communications (2020).