Visible-Light-Induced Dearomative Annulation of Indoles toward Stereoselective Formation of Fused- and Spiro Indolines

Abstract

Dearomatization approaches are attractive for their abilities to transform simple, planar arenes into complex, three-dimensional architectures. In particular, visible-light driven dearomatization strategies are significant because of their mild, green, and sustainable nature, enabling the fabrication of new chemical bonds via an electron transfer or energy transfer process. Indole compounds, being potentially bioactive and readily accessible, can be employed efficiently as building blocks for constructing diverse annulated frameworks under photocatalysis. Highly stereoselective radical cascade reactions of appropriate indole systems can provide complex cyclic scaffolds bearing multiple stereocenters. In fact, the past few years have witnessed the renaissance of dearomative cycloadditions of indoles via visible-light-induced photocatalysis. The present review highlights recent advances (2019-mid 2024) in visible-light-driven dearomative annulation of indoles leading to formation of polycyclic indolines, including angularly fused and spiro indolines. Most of the reactions described in this review are simple, providing quick access to the desired products. Additionally, characteristic reaction mechanisms are offered to provide an understand of how indole scaffolds show distinctive reactivity under photocatalytic conditions.

Figure 1

Representative examples of natural products containing an indoline skeleton.

Figure 2

Visible-light-induced formation of fused, angularly fused, and spiro-indolines from indole derivatives.

Scheme 1. Visible-Light-Driven Reaction between Tryptamines and Alkynyl Sulfones to Afford Pyrroloindoline Scaffolds in the Presence of Ir-Photocatalyst

Scheme 2. Light-Induced Assembly of Electron-Deficient Indoles and Glycines toward Lactam-Fused Indolines in the Presence of an Organic Photocatalyst

Scheme 3. Visible-Light Photocatalyzed Intermolecular Α-Aminomethyl/Carboxylative Dearomatization of Indoles with CO₂ and Radical Precursors

Scheme 4. Photocatalytic Synthesis of Prenylated Indolines from α-Silylamines and Indoles

Scheme 5. Rapid Access to Pyrroloindolines from N-Propargylindoles and Acyl Chlorides under Photocatalysis

Scheme 6. Tunable Photocatalytic C-H Functionalization and Dearomative Annulation Involving Indole-Tethered Ketones

Scheme 7. Visible-Light-Promoted Palladium-Catalysis of N-(2-Bromobenzoyl)indoles and Alkenes to Access Fused Indolines

Scheme 8. Photocatalytic Dearomative Arylcarboxylation of Indoles for Accessing Indoline-3-Carboxylic Acid Derivatives

Scheme 9. Direct Photoinduced Reductive Heck Cyclization of Indoles to Obtain Indolino-Isoindolones

Scheme 10. Dearomative Photoredox Radical–Polar Crossover Reaction of Pyridine-Tethered Indoles toward Fused Indoline Motifs

Scheme 11. Visible-Light-Assisted Dearomatization of N-(o-Haloarylformyl)indoles in an EDA Complex of Thiophenol for Accessing Indoline Derivatives

Scheme 12. Metallophotoredox Dearomatization of Indoles for Facile Entry to Indolo[2,3-c]isoquinolin-5-ones

Scheme 13. Intermolecular Aza-Paternò–Büchi Reaction of Indoles and N-Sulfonylimines Leading to Azetidine-Fused Pentacyclic Indolines

Scheme 14. Photocatalyst-Free Paternò–Büchi Reaction of Indoles and Aromatic Ketones for Affording Oxeto[2,3-b]indoles

Scheme 15. Visible-Light Excited Ag₃PO₄ (NPs) Assisted Synthesis of Benzofuroindolines

Scheme 16. Photoredox Asymmetric Dearomatization of Indole Derivatives with N-Hydroxycarbamates Promoted by Ir/CPA Dual Catalysis

Scheme 17. Imidazoacridine-Based Photosensitizer (ACR-IMAC) for [2 + 2] Photocycloaddition of Indoles and Olefins Resulting in Cyclobutane-Fused Indolines

Scheme 18. [2π + 2σ]-Photocycloaddition Reaction of Indoles with Bicyclo[1,1,0]butanes Affording Bicyclo[2,1,1]hexanes

Scheme 19. Cr^III-Photocatalyzed Dearomative [3 + 2] Cycloaddition between Indoles and Vinyldiazo Compounds to Afford Cyclopentene Fused Indolines

Scheme 20. Gd(III)-Photocatalysis Enabled a Dearomative [2 + 2] Cycloaddition/Ring Expansion Sequence with Indoles toward Cyclopenta[b]indolines

Scheme 21. Ir-Photoredox Catalyzed Stereoselective Synthesis of Hexahydrocarbazoles from Tryptophans and Acrylamides

Scheme 22. Synthesis of Cyclobutane-Fused Indolines via Photocatalytic Divergent Dearomatization of Indoles

Scheme 23. Visible-Light-Induced Intramolecular Dearomatization of Indole Derivatives to Access Cyclobutane-Fused Angular Tetracyclic Indolines

Scheme 24. [2 + 2] Photocyclization of 3-(Hexa-4,5-dienyl)indoles Sensitized by 3,4-Dimethoxy Acetophenone to Form Methylenecyclobutane Fused Angular Tetracyclic Indolines

Scheme 25. Intramolecular [2 + 2] Photocycloaddition of Indole Derivatives toward Indoline Embedded Cyclobutane-Fused Pyrrolidinones Using Ir(dFppy)₃ or Organic Photosensitizer

Scheme 26. Photoredox-Catalyzed [2 + 2] Cycloaddition of Enaminone Tethered Indoles to Furnish Cyclohepta[b]indoles

Scheme 27. Photocatalytic Cyclization of Indole-Alkyne Compounds with NaHSO₃ Leading to Indoline Fused Sulfonyl Polycycles

Scheme 28. Photochemical Transformation of Allene Tethered Indoles into Tetracyclic Cyclobutane-Fused Indoline Scaffolds Using an Aromatic Ketone Photosensitizer

Scheme 29. Visible-Light-Promoted Dearomative Cyclization of Olefin-Tethered Indoles Process to Prepare Cyclobutane Fused Polycyclic Indolines

Scheme 30. Dearomative [2 + 2] Cycloaddition of Indole-Tethered Alkynes with an Ir-Based Photosensitizer for the Synthesis of Cyclobutene-Fused Indolizidines

Scheme 31. Photocatalytic [2 + 2] Cycloaddition of Aliphatic Amine Bearing Indoles toward Strained Indolines

Scheme 32. Photocatalytic Dearomative [2 + 2] Cycloaddition of Indole-Tethered O-Methyl Oximes to Achieve Indoline-Fused Azetidines

Scheme 33. Visible-Light-Mediated [5 + 2]/[2 + 2] Cycloaddition Involving Indole-Tethered VCPs toward Cycloheptane/Cyclobutane-Fused Indolines

Scheme 34. Visible-Light-Driven Double Dearomative Cycloaddition of Arene-Tethered Indoles for the Construction of Bridged Cyclic Indolines

Scheme 35. Light-Induced Dearomative Spirocyclization of Indoles toward Spiroazetidine/Spiroindane Indolines

Scheme 36. Photoredox-Catalyzed Reaction of Indole-Substituted Bromodifluoroacetamide and Phosphine Oxide toward Synthesis of Spiroindolines

Scheme 37. Light-Promoted Catalyst-Free Dearomative Spirocyclization of Indole-Tethered Ynones and Thiols to Access Sulfur-Containing Spirocyclic Indolines

Scheme 38. Visible-Light-Mediated Spirocyclization of Indole Ynones with Diselenides to Obtain 3-Selenospiroindolines

Scheme 39. Photocatalytic Intermolecular Dearomative Cyclization of Indole-Derived Bromides with Alkynes Affording Spiroindolines

Scheme 40. Visible-Light-Initiated Dearomative Oxamination Reaction of Anilide-Tethered Indoles toward Spiroindolines

Scheme 41. Red-Light-Induced Cascade Trifluoromethylation and Dearomatization of Indole Derivatives with Umemoto’s Reagent to Access 3,3′-Spirocyclic Indolines

Scheme 42. Photocatalytic Radical Insertion Reaction of 3-(2-Isocyanobenzyl)-Indoles and Bromodifluoroacetates to Offer Spiro[indole-3,3′-quinoline] Derivatives

Scheme 43. Visible-Light-Induced Spirocyclization of 3-(2-Isocyanobenzyl)-Indoles with Diselenides, Affording Selenyl Spiro[indole-3,3′-quinoline] Derivatives

Scheme 44. Synthesis of Spiropiperidino Indolines via Blue LED Driven Cyclopropanation of Tryptamine Derivatives