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Synlett 2025; 36(14): 2049-2051
DOI: 10.1055/s-0043-1773528
DOI: 10.1055/s-0043-1773528
letter
Overcoming Substrate Bias in Radical Addition: Selective C3-Functionalisation of Indoles
Yizhe Lou and Maud Tregear acknowledge funding from AstraZeneca for a summer internship before their pursuit of a PhD.
Abstract
Radical chemistry provides complementary methods to traditional 2-electron mechanisms for indole functionalisation. Radical addition of electron-poor radicals to indoles is generally C2-selective. We hereby report that this substrate bias can be overcome through installing a bulky silyl group at the indole N–H bond, leading to a strategy for selective addition of electron-poor carbon-centred radicals at the 3-position.
Supporting Information
- Supporting information for this article is available online at https://doi.org/10.1055/s-0043-1773528.
- Supporting Information
Publication History
Received: 09 January 2025
Accepted after revision: 14 February 2025
Article published online:
01 April 2025
© 2025. Thieme. All rights reserved
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References and Notes
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- 13 Please refer to the Supporting Information for details of optimisation.
- 14 General Procedure Lutidine (0.116 mL, 1.0 mmol, 2.0 equiv.), diethyl 2-bromolalonate (85 mL, 0.50 mmol, 1.0 equiv.), and CHCl3 (0.5 mL) were added to the indole (0.50 mmol, 1.0 equiv.) under a nitrogen atmosphere. The mixture was illuminated with a PennOC M2 photoreactor (365 nm, 100% LED strength, stirring rate: 500 rpm, 30 °C) for 24 h. The mixture was diluted with EtOAc (10 mL), washed with 2 M HCl (10 mL), brine (10 mL), dried over Na2SO4, filtered, and concentrated. The crude product was purified by column chromatography.
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Examples: