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Synthesis 2025; 57(02): 362-379
DOI: 10.1055/a-2383-7416
DOI: 10.1055/a-2383-7416
short review
Special Topic Dedicated to Prof. H. Ila
Catalytic Intermolecular [4+2]-Cycloaddition toward the Stereoselective C2–C3 Annulation of Indoles
We are grateful for financial support from the Science and Engineering Research Board – Promoting Opportunities for Women in Exploratory Research (SERB – POWER) (SPG/2023/000022) and for a SERB-Core Research Grant (CRG/2023/007151). S.P. thanks the Council of Scientific & Industrial Research (CSIR), New Delhi for a Senior Research Fellowship (SRF). CDRI Communication No. 10856.
Abstract
Catalytic dearomative cycloaddition involving the C2–C3 bond of indoles is a powerful strategy for the synthesis of fused indoline scaffolds. Through dearomative cycloaddition/annulation, planar indole substrates can be readily transformed into rigid, three-dimensional polycyclic complex structures in one step. Molecules with architectural complexity are generally considered to have drug-like properties. Hence, annulation products have tremendous potential for discovering therapeutic properties, and this strategy has become an important part of the medicinal chemistry toolbox. Using appropriate catalyst control, desirable stereoselectivity can be achieved. Previous literature reports reveal that [3+2]-cycloadditions of indoles have been extensively studied. In contrast, the catalytic [4+2]-cycloaddition/dearomatization of indoles has been much less investigated. In this short review, we focus specifically on six-membered ring annulations via [4+2]-cycloaddition with the C2–C3 bond of indoles and discuss the various catalytic methods that have been developed toward this objective.
1 Introduction
2 [4+2]-Cycloaddition/Annulation of Indoles
2.1 Electron-Rich Indoles
2.1.1 Transition-Metal Catalysis
2.1.2 Organocatalysis
2.2 Electron-Deficient Indoles
2.2.1 Transition-Metal Catalysis
2.2.2 Organocatalysis
3 Summary and Outlook
Key words
cycloaddition - indoles - six-membered-ring annulation - transition-metal catalysis - organocatalysisPublication History
Received: 31 May 2024
Accepted after revision: 09 August 2024
Accepted Manuscript online:
09 August 2024
Article published online:
25 September 2024
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For selected reviews, see:
For selected papers on iminium catalysis, see:
For recent reviews on using iminium-enamine chemistry in cascade reactions, see:
For selected recent reviews, see: