Iodine-Catalyzed Highly Efficient Synthesis of 3-Alkylated/3-Alkenylated Indoles from 1,3-Dicarbonyl Compounds

Abstract

Molecular iodine has been found to be an efficient and inexpensive catalyst for the synthesis of 3-alkylated/3-alkenylated indoles in excellent yields by using different indoles and 1,3-dicarbonyl compounds at room temperature.

Key words

iodine - 3-alkenylated indoles - 1,3-dicarbonyl compounds - solvent-free - bis(indolyl)carbonyl compounds

• References and Notes

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• 9e Allam BK, Singh KN. Tetrahedron Lett. 2011; 52: 5851 General Experimental Procedure for the 3-Alkenylation/3-Alkylation of Indoles (Table 2) A mixture of indole (1 mmol), 1,3-dicarbonyl compound (1 mmol) and I₂ (10 mol%) was taken in a round-bottom flask and stirred at r.t. for the appropriate time (Table 2). After the completion of reaction as indicated by TLC, a sat. aq solution of Na₂S₂O₃ (2 × 5 mL) was added, and the mixture was extracted with EtOAc (3 × 5 mL). The combined organic phases were dried over anhyd Na₂SO₄, filtered, and evaporated under reduced pressure to furnish the crude product which was purified by column chromatography. Spectral Data of some Representative Products (E)-Ethyl-3-(2-methyl-1H-3-indolyl)-2-butenoate (3b) IR (KBr): 3411, 2933, 1718 cm^–1. ¹H NMR (300 MHz, CDCl₃): δ = 7.99 (br s, 1 H), 7.65 (d, 1 H, J = 7.5 Hz), 7.29–7.25 (m, 1 H), 7.17–7.09 (m, 2 H), 5.92 (s, 1 H), 4.25 (q, 2 H, J = 7.2 Hz), 2.66 (s, 3 H), 2.51 (s, 3 H), 1.35 (t, 3 H, J = 7.2 Hz). ¹³C NMR (75 MHz, CDCl₃): δ = 167.3, 152.0, 135.0, 132.7, 127.0, 121.7, 120.3, 119.5, 117.1, 116.8, 110.4, 59.5, 20.4, 14.4,13.4. Anal. Calcd for C₁₅H₁₇NO₂: C, 74.05; H, 7.04; N, 5.76. Found: C, 73.99; H, 7.06; N, 5.68. Ethyl 3,3-Bis(1H-3-indolyl)butanoate (4b) IR (KBr): 3406, 3351, 3056, 2938, 1724 cm^–1. ¹H NMR (300 MHz, CDCl₃): δ = 7.95 (br s, 2 H), 7.35–7.28 (m, 4 H), 7.10–7.03 (m, 4 H), 6.88 (t, 2 H, J = 7.5 Hz), 3.86 (q, 2 H, J = 7.2 Hz), 3.37 (s, 2 H), 2.08 (s, 3 H), 0.86 (t, 3 H, J = 7.2 Hz). Anal. Calcd for C₂₂H₂₂N₂O₂: C, 76.28; H, 6.40; N, 8.09. Found: C, 76.21; H, 6.25; N, 8.01. 4,4-Bis(5-bromo-1H-3-indolyl)pentan-2-one (4c) IR: 3342, 3321, 2966, 1680 cm^–1. ¹H NMR (300 MHz, CDCl₃): δ = 8.08 (br s, 2 H), 7.37 (m, 2 H), 7.20–7.13 (m, 6 H), 3.42 (s, 2 H), 1.95 (s, 3 H), 1.60 (s, 3 H). Anal. Calcd for C₂₁H₁₈Br₂N₂O: C, 53.19; H, 3.83; N, 5.91. Found: C, 53.11; H, 3.70; N, 5.84. Ethyl 3,3-Bis(5-bromo-1H-3-indolyl)butanoate (4d) IR (KBr): 3423, 3360, 2976, 1713 cm^–1. ¹H NMR (300 MHz, CDCl₃): δ = 8.06 (br s, 2 H), 7.37 (m, 2 H), 7.20–7.14 (m, 6 H), 3.89 (q, 2 H, J = 7.2 Hz), 3.28 (s, 2 H), 2.02 (s, 3 H), 0.91 (t, 3 H, J = 7.2 Hz). Anal. Calcd for C₂₂H₂₀Br₂N₂O₂: C, 52.41; H, 4.00; N, 5.56. Found: C, 53.33; H, 4.05; N, 5.51. 4,4-Bis(5-methoxy-1H-3-indolyl)pentan-2-one (4e) IR (KBr): 3408, 3360, 2934, 1695 cm^–1. ¹H NMR (300 MHz, CDCl₃): δ = 7.90 (br s, 2 H), 7.22–7.07 (m, 4 H), 6.76–6.73 (m, 4 H), 3.61 (s, 6 H), 3.46 (s, 2 H), 1.95 (s, 3 H), 1.57 (s, 3 H). Anal. Calcd for C₂₃H₂₄N₂O₃: C, 73.38; H, 6.43; N, 7.44. Found: C, 73.22; H, 6.43; N, 7.35. Ethyl 3,3-Bis(5-methoxy-1H-3-indolyl)butanoate (4f) IR (KBr): 3409, 3365, 2978, 1719 cm^–1. ¹H NMR (300 MHz, CDCl₃): δ = 7.87(br s, 2 H), 7.19–7.10 (m, 4 H), 6.74–6.71 (m, 4 H), 3.89 (q, 2 H, J = 7.2 Hz), 3.61 (s, 6 H), 3.33 (s, 2 H), 2.04 (s, 3 H), 0.90 (t, 3 H, J = 7.2 Hz). Anal. Calcd for C₂₄H₂₆N₂O₄: C, 70.92; H, 6.45; N, 6.89. Found: C, 70.83; H, 6.28; N, 6.78