Photochemical Reactions in Organic Synthesis

Photochemical reactions harness the energy of light to drive the formation and manipulation of organic molecules. By accessing excited‐state intermediates, chemists can initiate bond‐forming processes that are often challenging or unachievable under thermal conditions. Visible‐light photochemistry in particular has revolutionised the field by employing low‐energy, readily available light sources alongside organic or transition‐metal photocatalysts. This approach enables a variety of transformations—cycloadditions, hydrogen abstractions, electron‐transfer events and cascade sequences—under mild conditions with high regio- and stereocontrol. Recent advances have expanded the toolkit for constructing complex, three-dimensional frameworks and heterocycles, offering new solutions for pharmaceutical synthesis, agrochemical development and material science while adhering to principles of green chemistry.

Research from Nature Portfolio

Intermolecular aza-[2+2] photocycloaddition of indole derivatives has emerged as a powerful route to ladder-shaped azetidine-fused indoline pentacycles, enabling rapid assembly of rigid, three-dimensional scaffolds with contiguous quaternary centres under visible-light energy-transfer conditions. Mechanistic studies revealed that distortion-controlled C–N coupling governs regio- and stereoselectivity, broadening the repertoire of complex molecular architectures accessible by photochemistry. Cascade dearomative [2+2] cycloaddition/rearrangement of quinolines with alkenes has further demonstrated straightforward access to hybrid 2D/3D fused ring systems featuring multiple ring sizes and excellent diastereoselectivity via energy-transfer processes, with substitution patterns dictating divergence between cyclopropanation and cyclobutane rearrangement. Complementing these advances, chromophore activation strategies using chiral Brønsted acid organocatalysts have enabled enantio- and diastereoselective [2+2] photocycloadditions of simple substrates, showcasing stereocontrolled bond formation directly from excited states under mild, operationally simple conditions.

Photochemical Reactions in Organic Synthesis publication trend

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

Technical terms

Photocatalyst: A substance that absorbs light and facilitates a chemical reaction without being consumed.

Energy transfer: Transfer of excited-state energy from a photocatalyst to a substrate to initiate a reaction.

Photoredox catalysis: A mechanism involving light-induced electron transfer to activate substrates and form radicals or ions.

[2+2] photocycloaddition: A light-driven reaction that joins two π-bonds to form a four-membered ring.

Chromophore activation: Coordination or interaction of a catalyst with a substrate’s light-absorbing unit to alter its photophysical properties.

Enantioselectivity: The preferential formation of one enantiomer over its mirror image in a chiral reaction.

Diastereoselectivity: The preferential formation of one diastereomer over another when multiple stereoisomers are possible.

Triplet state: An excited electronic state of a molecule characterised by two unpaired electrons with parallel spins.

References

1. Accessing ladder-shape azetidine-fused indoline pentacycles through intermolecular regiodivergent aza-Paternò–Büchi reactions. Nature Communications (2024).
2. Facile access to fused 2D/3D rings via intermolecular cascade dearomative [2 + 2] cycloaddition/rearrangement reactions of quinolines with alkenes. Nature Catalysis (2022).
3. Chiral Brønsted acid-controlled intermolecular asymmetric [2 + 2] photocycloadditions. Nature Communications (2021).
4. Visible Light Photocatalysis of 6π Heterocyclization. Angewandte Chemie International Edition (2017).
5. Photo‐Organocatalytic Enantioselective Radical Cascade Reactions of Unactivated Olefins. Angewandte Chemie International Edition (2018).
6. Recent advances in visible-light-driven organic reactions. National Science Review (2017).