Radical Chemistry Applications in Organic Synthesis

Radical chemistry has transformed the way complex molecules are assembled by exploiting open-shell intermediates that engage in single-electron transfers under mild conditions. Modern strategies harness photoredox, electrochemical or catalytic activation to generate carbon-, nitrogen- and heteroatom-centred radicals with precise temporal and spatial control. These reactive species enable otherwise challenging bond formations, including difunctionalisation of alkenes and alkynes, remote C–H functionalisation, asymmetric radical cascades and ring-expansion processes. By obviating the need for strong oxidants or preactivated substrates, radical methods offer streamlined access to bioactive compounds, agrochemicals and advanced materials. The global significance of these approaches lies in their operational simplicity, sustainability and broad functional-group tolerance, which continue to expand the synthetic repertoire available to chemists.

Research from Nature Portfolio

Recent studies have demonstrated an electrochemical strategy that generates alkyl radicals directly from unactivated alkyl iodides via α-aminoalkyl radical-mediated halogen-atom transfer under mild, electricity-driven conditions. This protocol avoids sacrificial electrodes and external oxidants, exhibits excellent functional-group tolerance and is readily applied to the late-stage modification of complex biomolecules. In a complementary advance, enantioenriched arylsulfinylamides have been introduced as bifunctional reagents for visible-light-mediated asymmetric aminoarylation of internal alkenes. Under photoredox conditions, nitrogen addition and aromatic translocation occur in one operation to furnish β,β-diarylethylamines and related chiral amines with high regio-, diastereo- and enantiocontrol, while the sulfinyl auxiliary is eliminated in situ, streamlining the synthesis of pharmaceutically relevant motifs.

Radical Chemistry Applications in Organic Synthesis publication trend

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

Technical terms

Radical: A reactive intermediate bearing one or more unpaired electrons, capable of rapid single-electron transfers.

Photoredox catalysis: The use of light-activated catalysts to mediate single-electron transfer events for controlled radical generation and turnover.

Halogen-atom transfer (XAT): A mechanism in which a radical abstracts a halogen atom from an organic halide, generating a new radical species and a halogen-free by-product.

Radical-polar crossover: A transition from a radical intermediate to an ionic species, enabling subsequent nucleophilic or electrophilic reactions within a single sequence.

Enantiomeric enrichment: The selective formation or separation of one enantiomer over its mirror image, yielding an optically enriched product.

References

1. Electrochemical halogen-atom transfer alkylation via α-aminoalkyl radical activation of alkyl iodides. Nature Communications (2023).
2. Chiral arylsulfinylamides as reagents for visible light-mediated asymmetric alkene aminoarylations. Nature Chemistry (2024).
3. E‐Selective Radical Difunctionalization of Unactivated Alkynes: Preparation of Functionalized Allyl Alcohols from Aliphatic Alkynes. Advanced Science (2024).
4. Nitrogen-Centered Radicals in Functionalization of sp2 Systems: Generation, Reactivity, and Applications in Synthesis. Chemical Reviews (2022).