Sulfoxonium Ylide Chemistry in Organic Synthesis

Sulfoxonium ylides have emerged as versatile and stable carbene precursors in organic synthesis, offering safety and operational advantages over diazo compounds. These ylides facilitate diverse transformations including cyclopropanation, C–H insertion, cycloaddition and annulation under metal or photochemical catalysis. Mechanistically, the zwitterionic character enables controlled carbene transfer, while the sulfoxonium group serves as a handle for further functionalisation. Recent developments have expanded enantioselective protocols to deliver chiral building blocks for pharmaceuticals and natural product synthesis. Their bench stability, broad substrate scope and compatibility with green chemistry principles have catalysed global interest, driving applications in the scalable synthesis of heterocycles, amino acid derivatives and complex molecular frameworks for drug discovery and materials science.

Research from Nature Portfolio

Recent studies have introduced a new class of hypervalent iodine reagents bearing transferrable sulfoxonium groups, enabling visible-light-promoted cycloadditions with alkenes, alkynes, allenes and nitriles under mild conditions. These well-defined reagents access two complementary cyclization pathways controlled by substrate substitution, and permit further transformation of the sulfoxonium handle into diverse functionalities via single-electron transfer and transition-metal catalysis. This work broadens the scope of sulfoxonium-ylide-mediated bond constructions, demonstrating excellent functional-group tolerance, operational simplicity and potential for late-stage molecular diversification.

Sulfoxonium Ylide Chemistry in Organic Synthesis publication trend

The graph below shows the total number of articles in sulfoxonium ylide chemistry in organic synthesis across all publications each year (not limited to Nature Index journals).

Technical terms

Sulfoxonium ylide: An organosulfur compound bearing a positive charge on sulfur and an adjacent carbanion, used as a stable precursor for carbene-transfer reactions.

Carbene: A highly reactive species featuring a neutral carbon atom with two non-bonded electrons, capable of undergoing insertions, cycloadditions and rearrangements.

Enantioselectivity: The preferential formation of one enantiomer over another in a chiral reaction, typically quantified by enantiomeric excess.

Cycloaddition: A pericyclic reaction in which two or more unsaturated molecules combine to form a cyclic product, often facilitated by catalysts or light.

C–H activation: A catalytic process in which a carbon–hydrogen bond is cleaved and transformed into a new carbon–carbon or carbon–heteroatom bond, expanding synthetic access to functionalised frameworks.

References

1. Asymmetric transformations from sulfoxonium ylides. Chemical Science (2022).
2. Cooperative copper-squaramide catalysis for the enantioselective N–H insertion reaction with sulfoxonium ylides. Chemical Science (2021).
3. Enantioselective Intramolecular Iridium-Catalyzed Cyclopropanation of α‑Carbonyl Sulfoxonium Ylides. Organic Letters (2022).
4. Synthesis of I(III)/S(VI) reagents and their reactivity in photochemical cycloaddition reactions with unsaturated bonds. Nature Communications (2022).