Hypervalent Iodine Chemistry in Organic Synthesis

Hypervalent iodine chemistry has emerged as a versatile and environmentally benign platform for the construction of carbon–carbon and carbon–heteroatom bonds in modern organic synthesis. At the heart of this field are iodine(III) and iodine(V) reagents, whose three-centred four-electron bonds afford high reactivity toward electrophilic functionalisation, oxidative rearrangements and group-transfer processes. Iodonium salts, benziodoxoles and related frameworks serve both as stoichiometric oxidants and catalytic mediators, enabling halogenation, amination, azidation and alkynylation under mild conditions. The unique electronic structure of hypervalent iodine species confers selectivity that is often unattainable with conventional reagents, while their low toxicity and ready availability enhance sustainability. Recent advances have focused on chiral hypervalent iodine catalysts for enantioselective transformations, the design of polymer- or nanoparticle-supported reagents for recyclability and the integration of photochemical or electrochemical activation modes. These innovations not only streamline classical two-electron redox pathways but also uncover alternative single-electron and open-shell mechanisms. Collectively, hypervalent iodine chemistry continues to expand the synthetic toolbox, delivering practical solutions for complex molecule construction in both academic and industrial settings across the globe.

Research from Nature Portfolio

Recent studies have demonstrated the utility of iodine(I/III) electrocatalysis in continuous-flow systems for regioselective chlorination and cyclisation reactions. By coupling electrochemical oxidation of iodoarenes with in situ formation of dichloroiodoarene mediators, mono- and dichlorination of alkenes can be achieved under milder conditions and with enhanced throughput. This approach exploits the tunable redox potential of hypervalent iodine species, minimises waste and enables scalable production of chlorinated building blocks for pharmaceutical and agrochemical targets.

Hypervalent Iodine Chemistry in Organic Synthesis publication trend

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

Technical terms

Hypervalent iodine: A class of iodine compounds with more than eight electrons around the iodine centre, exhibiting expanded valence shells.

Iodonium salt: A positively charged iodine(III) species with two organic ligands, often used for arylation or alkynylation reactions.

Iodanyl radical: A transient open-shell iodine(II) intermediate formed by single-electron processes, involved in novel catalytic cycles.

Group-transfer reagent: A compound that delivers functional groups (e.g., azido, alkynyl) to organic substrates through polar or radical pathways.

Three-centred four-electron (3c-4e) bond: A bonding arrangement in hypervalent iodine compounds where one iodine atom shares electrons with two ligands in a delocalised framework.

References

1. Recent Progress in Synthetic Applications of Hypervalent Iodine(III) Reagents. Chemical Reviews (2024).
2. Iodanyl Radical Catalysis. Accounts of Chemical Research (2023).
3. Electrocatalytic continuous flow chlorinations with iodine(I/III) mediators. Nature Communications (2024).
4. Progress in organocatalysis with hypervalent iodine catalysts. Chemical Society Reviews (2022).