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Outbyte PC Repair FREERepair Windows errors before they cause bigger problemsFix Now →Outbyte Driver Updater FREEScan for outdated or missing drivers - takes under a minuteDriver Scan →A 2023 method from Patrick Finkelstein, Julia C. Reisenbauer, Bence B. Botlik, Ori Green, Andri Florin and Bill Morandi’s group at ETH Zürich turns indenes into isoquinolines by inserting a nitrogen atom into the existing five-membered carbon ring. The reported reaction uses phenyliodine(III) diacetate (PIDA) and ammonium carbamate; it offers a way to edit a carbocyclic precursor rather than assemble the heterocycle from separate fragments.
What changes in the skeletal edit?
An indene has a fused-ring framework with a five-membered carbon ring. In the reported transformation, a nitrogen atom is inserted into that ring, changing the carbon skeleton into the nitrogen-containing framework of an isoquinoline. The strategic shift is the starting point: instead of constructing the isoquinoline ring system from pre-oxidized building blocks and amines, or oxidizing a di- or tetrahydroisoquinoline, the method modifies an existing carbocyclic scaffold. The authors frame this as an alternative to those approaches, not as a replacement for every route to isoquinolines.
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The study, “Nitrogen atom insertion into indenes to access isoquinolines,” appeared in Chemical Science in 2023. It was submitted on 19 December 2022, accepted on 14 February 2023, and first published on 23 February 2023. Royal Society of Chemistry publication details.
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The authors report using commercially available phenyliodine(III) diacetate (PIDA) and ammonium carbamate. PIDA is the reaction reagent, while ammonium carbamate supplies the nitrogen incorporated into the ring. The reported protocol does not rely on a transition-metal catalyst, a feature the group linked to functional-group tolerance in comments reported by Chemistry World.
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This is a description of the published reaction, not a complete bench procedure: exact quantities, solvent, temperature, work-up and substrate-specific results should be taken from the primary article and its supporting information rather than inferred from the reagent names alone. The Royal Society of Chemistry describes the work as a protocol for nitrogen-atom insertion into indenes to afford isoquinolines: primary article.
What substrate scope did the authors report?
The paper reports isoquinolines with varied substitution patterns and functional groups tolerated across the substrates examined. Chemistry World reports that the team tested 25 indene precursors. That count describes the set reported in this study; it does not establish that every indene, substitution pattern or sensitive functional group will work. Individual outcomes depend on the substrate and should be checked in the paper’s examples.
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The authors also extended the reaction concept beyond indenes: cyclopentadienes were converted into corresponding pyridines. This demonstrates a related ring-system application, but does not by itself establish compatibility with other classes of carbocycles.
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Can the reaction make nitrogen-15-labelled isoquinolines?
Yes. The authors report using 15NH4Cl as a nitrogen-15 source to obtain labelled isoquinolines. This provides a route to introduce an isotope label at the nitrogen atom during skeletal editing. The reported result establishes access to labelled examples; it is not evidence that every substrate or isotopic labelling goal has been demonstrated.
Independent reader supportYour contribution helps us test, update, and keep practical guides available for everyone.How should the method be weighed against other routes?
The distinctive feature is late-stage nitrogen insertion into an indene carbon framework. That can be strategically useful when the corresponding carbocyclic precursor is accessible and a direct edit better fits the synthesis than building the heterocycle from fragments. The paper discusses earlier oxidative-cleavage approaches and other direct approaches with substrate or reagent limitations as context for its contribution. Those comparisons are the authors’ framing, not a comprehensive assessment of every current isoquinoline synthesis.
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- Precursor strategy: starts from an indene rather than prefunctionalized fragments used to assemble the heterocycle.
- Nitrogen installation: introduces nitrogen during the skeletal edit, using ammonium carbamate in the reported indene reaction.
- Demonstrated reach: reported indene examples include varied substitution patterns and tolerated functional groups; the authors also showed cyclopentadiene-to-pyridine conversion and nitrogen-15 labelling.
- Practical boundary: the documented substrate set supports a useful method, not a universal solution. Assess the specific substrate and conditions in the paper before relying on the transformation in a synthesis plan.
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