Synthetic Methodologies for Indenone Derivatives

The indenone core, characterised by a fused benzene and cyclopentenone system, has garnered attention due to its presence in natural products, pharmaceuticals and materials. Synthetic access to indenones and their derivatives has evolved from classical Friedel–Crafts acylations and transition-metal-catalysed cyclisation strategies to modern radical, photoredox and organocatalytic methods. Recent advances emphasise mild conditions, operational simplicity and broad functional-group tolerance, enabling the construction of highly substituted and enantioenriched indenones. These methodologies often invoke intramolecular annulation of alkynyl or alkenyl precursors, radical-triggered cyclisations, C–H activation and decarboxylative couplings. Acid-mediated protocols and Lewis or Brønsted acid catalysis continue to deliver diverse substitution patterns, including trifluoromethylated and cyano-incorporated frameworks. Photochemical processes, leveraging visible-light-driven electron transfers, have further enhanced atom- and step-economy, opening routes to complex indenone architectures under ambient conditions. Collectively, this toolbox facilitates rapid access to core structures for drug discovery, agrochemistry and organic electronics, underscoring the global significance of indenone synthesis.

Research from Nature Portfolio

Recent studies have introduced a hydrogen radical-shuttle-enabled photoredox decarboxylative annulation for the construction of indenone analogues. This strategy employs visible-light photocatalysis to generate carbon radicals from carboxylic acid derivatives. Water acts as both radical shuttle and hydrogen source, promoting intramolecular hydrogen atom transfer over challenging 1,2- or 1,3-distances. The protocol proceeds under mild conditions, displays broad substrate scope and delivers functionalised indenones with high atom- and step-economy.

Synthetic Methodologies for Indenone Derivatives publication trend

The graph below shows the total number of articles in synthetic methodologies for indenone derivatives across all publications each year (not limited to Nature Index journals).

Technical terms

Indenone: A bicyclic compound comprising a benzene ring fused to a cyclopentenone moiety.

Photoredox catalysis: A process using visible-light-absorbing catalysts to drive redox reactions via photoexcited electron transfer.

Hydrogen atom transfer (HAT): A mechanism in which a hydrogen atom, including its electron, is transferred between molecular species, often mediated by radicals.

Decarboxylative annulation: A cyclisation reaction that forms a ring by coupling fragments with concurrent loss of carbon dioxide.

Lewis acid: An electron-pair acceptor that activates substrates for electrophilic reactions.

Trichloromethylation: Introduction of a CCl₃ group, often via radical or electrophilic pathways, to impart strong electron-withdrawing character.

References

1. Lewis acid-mediated transformations of 5-acyl- N -fluoroalkyl-1,2,3-triazoles to cyclopentenones, indenones, or oxazoles. RSC Advances (2024).
2. Hydrogen radical-shuttle (HRS)-enabled photoredox synthesis of indanones via decarboxylative annulation. Nature Communications (2021).
3. Copper-Catalyzed Annulation–Cyanotrifluoromethylation of 1,6-Enynes Toward 1-Indanones via a Radical Process. Frontiers in Chemistry (2020).
4. Cyclization of 1-aryl-4,4,4-trichlorobut-2-en-1-ones into 3-trichloromethylindan-1-ones in triflic acid. Beilstein Journal of Organic Chemistry (2023).