Visible Light-Driven Radical Reactivity in Organic Synthesis

Visible light-driven radical processes have transformed the landscape of organic synthesis by enabling mild, selective and sustainable bond‐forming reactions. By harnessing photons in the visible region, photocatalysts—ranging from transition‐metal complexes to organic dyes—are promoted to excited states that facilitate single‐electron transfer events. Such activation generates carbon‐, nitrogen‐ and oxygen‐centred radicals under ambient conditions, obviating the need for harsh reagents or high temperatures. The resultant radicals engage in diverse pathways, including radical addition to unsaturated bonds, cascade cyclisations, remote functionalisation via intramolecular hydrogen atom transfer (HAT) and β-scission, and cross‐coupling with external partners. These approaches afford rapid access to complex scaffolds, support late‐stage modification of bioactive molecules and reduce the environmental footprint of traditional methodologies. Recent advances have extended the scope to heterocycle assembly, site-selective C–H bond activation and umpolung strategies in alkene functionalisation, underscoring the global significance and wide applicability of visible light-mediated radical reactivity in modern synthesis.

Research from Nature Portfolio

Researchers have developed a copper-catalysed protocol for remote sp³ C–H alkynylation that proceeds through visible light-induced generation of an iminyl radical from an O-acyloxime precursor. Photoexcitation of a Cu(I)–terpyridine complex triggers reductive cleavage of the N–O bond, forming an iminyl radical that undergoes either β-scission or 1,5-HAT to yield a distal carbon radical. Subsequent copper-catalysed coupling with terminal alkynes furnishes γ- and δ-alkynyl nitriles or ketones in a single pot. The method tolerates complex natural product frameworks and offers a general route to alkynylated building blocks under mild conditions.

Visible Light-Driven Radical Reactivity in Organic Synthesis publication trend

The graph below shows the total number of articles in visible light-driven radical reactivity in organic synthesis across all publications each year (not limited to Nature Index journals).

Technical terms

Photocatalysis: Use of light‐absorbing catalysts to mediate chemical transformations via photoexcited states.

Radical translocation: Intramolecular shift of a radical centre along a molecular chain, often via hydrogen atom transfer.

Iminyl radical: Nitrogen‐centred radical species derived from cleavage of an oxime or related N–O bond.

Hydrogen atom transfer (HAT): Radical process in which a hydrogen atom (proton plus electron) moves between two species.

β-Scission: Fragmentation of a radical intermediate at the carbon atom adjacent to the radical centre, yielding a new radical and a neutral fragment.

References

1. Photoinduced Remote Functionalisations by Iminyl Radical Promoted C−C and C−H Bond Cleavage Cascades. Angewandte Chemie International Edition (2017).
2. Visible‐Light‐Mediated Generation of Nitrogen‐Centered Radicals: Metal‐Free Hydroimination and Iminohydroxylation Cyclization Reactions. Angewandte Chemie International Edition (2015).
3. Photoredox Imino Functionalizations of Olefins. Angewandte Chemie International Edition (2017).
4. Functionalization of remote C(sp3)-H bonds enabled by copper-catalyzed coupling of O-acyloximes with terminal alkynes. Nature Communications (2020).