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Synlett 2007(11): 1775-1779  
DOI: 10.1055/s-2007-982572
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© Georg Thieme Verlag Stuttgart · New York

Gold-Catalyzed Synthesis of 2-Substituted, 2,3-Disubstituted and 1,2,3-Trisubstituted Indoles in [bmim]BF4

Ilaria Ambrogioa, Antonio Arcadib, Sandro Cacchia, Giancarlo Fabrizia, Fabio Marinelli*b
a Dipartimento di Studi di Chimica e Tecnologia delle Sostanze Biologicamente Attive, Università degli Studi ‘La Sapienza’, P. le A. Moro 5, 00185 Rome, Italy
b Dipartimento di Chimica, Ingegneria Chimica e Materiali, Università di L’Aquila, Via Vetoio, Coppito Due, 67010 L’Aquila, Italy
Fax: +39(0862)433753; e-Mail: fmarinel@univaq.it;
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Publication History

Received 1 March 2007
Publication Date:
25 June 2007 (online)

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Abstract

Cyclization of 2-alkynylanilines in the presence of NaAuCl4·H2O using [bmim]BF4 as the reaction medium afforded 2-substituted indoles in high yields. The catalyst system was best recycled using n-Bu4NAuCl4. 2,3-Disubstituted indoles could be prepared from 2-alkynylanilines and 3-buten-2-one through a one-flask annulation-alkylation sequence and 1,2,3-trisubstituted indoles were obtained from the same starting materials via an aza-Michael addition-annulation-alkylation process.

Key words

gold catalysis - ionic liquids - indoles - hydroamination - aza-Michael addition

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[bmim]AuCl4 was prepared as follows: To a magnetically stirred solution of [bmim]Cl (0.0458 g, 0.263 mmol) in CH2Cl2 (5 mL) was added NaAuCl4·H2O (0.100 g, 0.263 mmol) and the reaction was allowed to stand at r.t. for 4 h. Then, the mixture was extracted with CH2Cl2 (100 mL) and H2O (2 × 50 mL). The organic layer was dried (Na2SO4) and evaporated to give [bmim]AuCl4 as a yellow powder (0.120 g).

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Representative Procedure: To 2-(dec-1-ynyl)aniline (1f; 0.059 g, 0.26 mmol) in [bmim]BF4 (1 mL) was added NaAuCl4·2H2O (0.001 g, 1 mol%). The mixture was stirred at 50 °C for 24 h. The mixture was diluted with Et2O (100 mL) and washed with brine. The Et2O layer was dried (Na2SO4) and concentrated in vacuo and the residue was purified by flash chromatography on silica gel giving 2f (54 mg, 92% yield); mp 50-51 °C. IR (KBr): 3413, 2923, 1457, 1408, 774 cm-1. 1H NMR (CDCl3): δ = 7.86 (br s, 1 H), 7.57 (d, J = 7.6 Hz, 1 H), 7.32 (d, J = 7.7 Hz, 1 H), 7.25 (dt, J 1 = 7.7 Hz, J 2 = 1.3 Hz, 1 H), 7.11 (dt, J 1 = 7.6 Hz, J 2 = 1.0 Hz, 1 H), 6.27 (s, 1 H), 2.78 (t, J = 7.6 Hz, 2 H), 1.75 (quin, J = 7.5 Hz, 2 H), 1.23-1.48 (m, 10 H), 0.93 (t, J = 7.6 Hz, 3 H). 13C NMR (CDCl3): δ = 140.1, 136.9, 128.9, 121.0, 119.8, 119.6, 110.3, 99.5, 31.9, 29.5, 29.4, 29.28, 29.26, 28.3, 22.7, 14.2. Anal. Calcd for C16H23N: C, 83.79; H, 10.11; N, 6.11. Found: C, 83.71; H, 10.13; N, 6.15. MS: m/z (%relative intensity) = 229 (50) [M+], 144 (41), 131 (81), 130 (100).

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Recycling Procedure: To a solution of 1a (0.100 g, 0.52 mmol) in [bmim]BF4 (2 mL) was added n-Bu4NAuCl4 (0.003 g, 1 mol%). The mixture was stirred at 50 °C for 24 h. The product was extracted from the reaction mixture by addition of Et2O (5 × 10 mL). The Et2O layer was separated. The ionic liquid layer containing the gold catalyst was pumped for several minutes and reused.