Visible-Light-Promoted Indole C-3 Formylation Using Eosin Y as a Photoredox Catalyst

Abstract

A visible-light-mediated C-3 formylation of indole catalyzed by eosin Y has been developed using tetramethylethylenediamine as a carbon source and air as an oxidant. This protocol shows high tolerance to a large quantity of functional groups under mild conditions and provides 3-formylated indoles with good yields. This method is a highly attractive alternative to the approach of traditional formylation.

Key words

visible light - eosin Y - air oxidant - indole formylation - photoredox

Publication History

Received: 30 January 2022

Accepted after revision: 18 February 2022

Accepted Manuscript online:
21 February 2022

Article published online:
25 March 2022

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• 20 General Procedure for Indole FormylationThe substrate 1 (0.5 mmol), TMEDA (2 equiv, 1 mmol), EY (0.1 equiv, 0.05 mmol), KI (4 equiv, 2 mmol), MeCN (5 mL), and H₂O (1 mL) were successively added to a 10 mL reaction bottle. The reaction was irradiated by two 450 nm blue LED lamps and stirred at room temperature under air. After a certain time period, the end of the reaction was confirmed by TLC. The desired product 3 was concentrated under vacuum and purified by silica gel chromatography with petroleum ether–ethyl acetate.1-Methyl-1-H-indole-3-formaldehyde (3b)Prepared according to the general procedure. Purification by column chromatography (petroleum ether–ethyl acetate, 3:2) gave 3b in 54% yield as a yellow solid (mp 154.7–156.6 °C). ¹H NMR (400 MHz, CDCl₃): δ = 9.95 (s, 1 H), 8.38–8.26 (m, 1 H), 7.62 (s, 1 H), 7.36–7.30 (m, 3 H), 3.83 (s, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 184.30, 139.18, 137.81, 125.19, 123.93, 122.83, 121.93, 117.98, 109.79, 33.55.