CsOH-Promoted Regiospecific Sulfenylation, Selenylation, and Telluration of Indoles in H₂O

Abstract

Various indole-containing compounds have shown impressive pharmaceutical activities against a variety of diseases. However, the functionalization of indoles usually relies on systems that use organic solvents, which do not meet the criteria for green and sustainable chemical development. To address this issue, regiospecific sulfenylation, selenylation, and telluration of indoles were developed using H₂O as solvent. The highly efficient chalcogenylation of indoles was achieved utilizing CsOH as a promoter, thus avoiding the use of expensive transition-metal catalysts. This newly developed protocol is characterized by its outstanding features including simple operation, mild conditions, wide substrate scope, excellent functional group tolerance, and recyclability, leading to the convenient synthesis of 3-chalcogenyl-indoles.

Key words

indole - regiospecific - chalcogenation - H₂O

Publication History

Received: 07 April 2022

Accepted after revision: 20 June 2022

Accepted Manuscript online:
20 June 2022

Article published online:
20 July 2022

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• 22 Typical Procedure for the Synthesis of 3-(Phenylthio)-1H-indole Indole (0.5 mmol), diphenyl disulfide (0.25 mmol), CsOH·H₂O (0.75 mmol), and H₂O (0.2 mL) were added. Then the mixture was stirred at 70 °C, under air for 5 h. After the reaction finished, the mixture was extracted with ethyl acetate (3 × 3.0 mL). The upper layer of the organic phase is slowly drawn out with a syringe. The remaining trace water phase is used for the next cycle. The organic phase was dried over Na₂SO₄ and concentrated under vacuum. The residue was purified by flash chromatography on silica gel to afford give a white solid 3a;^18a 104.7 mg, 93% yield. ¹H NMR (400 MHz, CDCl₃): δ = 8.39 (s, 1 H), 7.61 (d, J= 7.6 Hz, 1 H), 7.46 (d, J= 2.4 Hz, 1 H), 7.42 (d, J= 8.4 Hz, 1 H), 7.28–7.24 (m, 1 H), 7.18–7.13 (m, 3 H), 7.10 (d, J = 7.6 Hz, 2 H), 7.06–7.03 (m, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 139.3, 136.5, 130.7, 129.1, 128.7, 125.9, 124.8, 123.1, 120.9, 119.7, 111.6, 102.8. MS: m/z = 225.3 [M⁺].