Cascade Radical Cyclization in Chroman Derivatives

Cascade radical cyclization in chroman derivatives has emerged as a powerful strategy for the rapid construction of complex oxygen-containing heterocycles. This approach exploits the generation of radical intermediates that undergo sequential intramolecular additions to afford chroman frameworks in a single operation. The methodology enables the simultaneous formation of multiple carbon–carbon and carbon–heteroatom bonds, offering high step economy and functional group tolerance. Radical generation often proceeds under mild, metal-free or photocatalytic conditions, employing oxidants such as persulfates or visible-light-activated catalysts to trigger decarboxylations or initiate radical annulation sequences. The resulting chroman derivatives, including chroman-4-ones and homoisoflavonoid analogues, are of considerable interest due to their prevalence in bioactive natural products and potential applications in medicinal chemistry. Recent innovations have focused on broadening the scope of radical precursors, from oxalates and oxamic acids to cyanoarenes, and on enhancing reaction selectivity through solvent control or catalyst design. Ongoing advances continue to improve sustainability and scalability, underscoring the global significance of this versatile synthetic platform.

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Cascade Radical Cyclization in Chroman Derivatives publication trend

The graph below shows the total number of articles in cascade radical cyclization in chroman derivatives across all publications each year (not limited to Nature Index journals).

Technical terms

Cascade radical cyclization: A sequence of radical-mediated bond-forming steps in which an initial radical generates additional radicals that undergo successive intramolecular cyclisations to build complex ring systems.

Chroman-4-one: An oxygen-containing heterocycle characterised by a bicyclic benzopyranone core, frequently encountered in natural products and pharmaceuticals.

Radical annulation: A process in which a radical species adds to an unsaturated moiety, forming a new ring (annulated structure) in the product.

Decarboxylation: The removal of a carboxyl group from a molecule, releasing carbon dioxide and often generating a reactive radical intermediate.

Photoredox catalysis: A catalytic approach using light-absorbing photocatalysts to promote single-electron transfer events, facilitating radical formation under mild conditions.

References

1. Synthesis of Ester-Containing Chroman-4-Ones via Cascade Radical Annulation of 2-(Allyloxy)Arylaldehydes with Oxalates under Metal Free Conditions. International Journal of Molecular Sciences (2023).
2. Metal-Free Synthesis of Carbamoylated Chroman-4-Ones via Cascade Radical Annulation of 2-(Allyloxy)arylaldehydes with Oxamic Acids. Molecules (2022).
3. Redox-neutral and metal-free synthesis of 3-(arylmethyl)chroman-4-ones via visible-light-driven alkene acylarylation. Frontiers in Chemistry (2022).