Synthesis of 3,3′-Disubstituted Indolenines Utilizing the Lewis Acid Catalyzed Alkylation of 2,3-Disubstituted Indoles with Trichloroacetimidates

Arijit A. Adhikari; Léa Radal; John D. Chisholm

doi:10.1055/s-0036-1588491

Synlett, Table of Contents

Synlett 2017; 28(17): 2335-2339
DOI: 10.1055/s-0036-1588491

letter

Synthesis of 3,3′-Disubstituted Indolenines Utilizing the Lewis Acid Catalyzed Alkylation of 2,3-Disubstituted Indoles with Trichloroacetimidates

Authors

Arijit A. Adhikari

Department of Chemistry, Syracuse University, 1-014 Center for Science and Technology, Syracuse, NY 13244-4100, USA Email: jdchisho@syr.edu
Léa Radal

Department of Chemistry, Syracuse University, 1-014 Center for Science and Technology, Syracuse, NY 13244-4100, USA Email: jdchisho@syr.edu
John D. Chisholm *

Department of Chemistry, Syracuse University, 1-014 Center for Science and Technology, Syracuse, NY 13244-4100, USA Email: jdchisho@syr.edu

Abstract

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Abstract

Trichloroacetimidates function as effective electrophiles for the selective C3-alkylation of 2,3-disubstituted indoles to provide 3,3′-disubstituted indolenines. These indolenines are common synthetic intermediates that are often utilized in the synthesis of complex molecules. Effective reaction conditions utilizing Lewis acid catalysts have been determined, and the scope of the reaction with respect to indole and imidate reaction partner has been investigated. This chemistry provides an alternative to base promoted and transition-metal-catalyzed methods that are more commonly utilized to access similar indolenines.

Key words

indole - trichloroacetimidate - alkylation - indolenine - Lewis acid - catalysis

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References

References and Notes

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17 Representative Procedure for C3-Alkylation of 2,3-Disubstituted Indoles with Trichloroacetimidates In a flame-dried flask allyl trichloroacetimidate 7 (121 mg, 0.60 mmol) was dissolved in 4 mL of anhydrous DCE. 2,3-Dimethylindole (6, 130 mg, 0.90 mmol) was then added followed by freshly distilled TMSOTf (20 mol%, 27 μL, 0.12 mmol). After 3 h at rt the reaction mixture was quenched with the addition of 10 mL of 1 M NaOH. The organic layer was separated, and the aqueous layer was extracted with CH₂Cl₂ (2 × 5 mL). The combined organic extracts were dried over Na₂SO₄, filtered, and concentrated. The residue was purified by silica gel chromatography (30% EtOAc/70% hexanes) to provide 2,3-dimethyl-3-(prop-2-en-1-yl)-3H-indole (8) as a yellow oil (82.0 mg, 74%). TLC R_f = 0.11 (10% EtOAc/90% hexanes). IR (neat): 3079, 3009, 2966, 2827, 2869, 1579 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 7.52 (d, J = 8.0 Hz, 1 H), 7.33–7.21 (m, 2 H), 7.19 (td, J = 7.2, 0.8 Hz, 1 H), 5.21–5.11 (m, 1 H), 4.98–4.85 (m, 2 H), 2.66–2.60 (m, 1 H), 2.42 (dd, J = 14.0, 8.0 Hz, 1 H), 2.26 (s, 3 H), 1.31 (s, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 186.6, 154.2, 143.4, 132.5, 127.7, 125.0, 121.8, 119.8, 118.0, 57.5, 41.2, 21.8, 15.9. This compound has been reported previously.^8f

Supplementary Material

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