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

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.

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

References and Notes

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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.

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