First Example of Functionalization of Activated Quinolines by Indoles Using CeCl₃·7H₂O [1]

Abstract

Indoles undergo smooth addition to activated quinolines and isoquinolines in the presence of CeCl₃·7H₂O under extremely mild conditions to provide 2-(1H-3indolyl)-1,2-dihydroquinolines and isoquinolines in excellent yields with high selectivity. It is ­entirely a new protocol to functionalize both indoles and quinolines in a single-step operation.

aza-aromatics - indolyl quinolines - cerium compounds

References

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IICT Communication No: 050804.

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General Procedure.
To a stirred solution of quinoline (1 mmol) in of MeCN (3 mL) was added ethyl chloroformate (1.5 mmol) slowly at 0 °C and the mixture stirred at this temperature for 30 min. To the resulting N-acyliminium ion was added CeCl₃·7H₂O (0.3 mmol) and indole (1 mmol) at r.t. and the resulting mixture stirred for the appropriate time (Table [1] ). After complete conversion as indicated by TLC, the reaction mixture was quenched with H₂O (10 mL) and extracted with CH₂Cl₂ (2 × 15 mL). The combined extracts were dried over anhyd Na₂SO₄, and concentrated in vacuo. The resulting product was purified by column chromatography on silica gel (Merck, 100-200 mesh, EtOAc-hexane, 2:8) to afford a pure 2-(3-indolyl)-1,2-dihydroquinoline.

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Spectroscopic Data for Selected Products.
Compound 3a: ¹H NMR (300 MHz, CDCl₃): δ = 7.86 (s, 1 H), 7.78 (d, 1 H, J = 5.9 Hz), 7.32 (br s, 1 H), 7.19 (d, 1 H, J = 7.4 Hz), 7.13-6.98 (m, 5 H), 6.78 (s, 1 H), 6.62 (d, 1 H, J = 9.7 Hz), 6.53 (d, 1 H, J = 4.5 Hz), 6.25 (dd, 1 H, J = 5.9, 2.9 Hz), 4.35 (m, 2 H), 1.40 (t, 3 H, J = 7.4 Hz). IR (KBr): ν = 3334, 3050, 2985, 1684, 1533, 1489, 1394, 1310, 1232, 1119, 1039, 752 cm^-1. FAB-MS: m/z = 318 [M⁺], 289, 273, 245, 218, 202, 158, 130, 103, 77, 57.
Compound 3f: ¹H NMR (300 MHz, CDCl₃): δ = 7.80 (br s, 2 H), 7.25 (s, 1 H), 7.20 (d, 1 H, J = 7.5 Hz), 7.14-7.03 (m, 2 H), 6.91 (s, 1 H), 6.87 (d, 1 H, J = 8.3 Hz), 6.80 (d, 1 H, J = 4.3 Hz), 6.58 (d, 1 H, J = 9.0 Hz), 6.51 (d, 1 H, J = 3.7 Hz), 6.24 (dd, 1 H, J = 6.0, 3.0 Hz), 4.30 (m, 2 H), 2.30 (s, 3 H), 1.40 (t, 3 H, J = 7.4 Hz). IR (KBr): ν = 3325, 3046, 2982, 1664, 1494, 1386, 1321, 1266, 1223, 1110, 1018, 742, 645 cm^-1. FAB-MS: m/z = 332 [M⁺] 287, 259, 216, 172, 154, 136, 107, 69, 55.
Compound 3j: ¹H NMR (300 MHz, CDCl₃): δ = 7.87 (s, 1 H), 7.72 (d, 1 H, J = 5.9 Hz), 7.22 (s, 1 H,), 7.15-7.01 (m, 5 H), 6.98 (s, 1 H), 6.86 (d, 1 H, J = 2.2 Hz), 6.62 (s, 1 H), 4.36 (q, 2 H, J = 14.1, 7.4 Hz), 1.38 (t, 3 H, J = 7.4 Hz). IR (KBr): ν = 3416, 3051, 2987, 1673, 1555, 1481, 1320, 1248, 1119, 1018, 886, 743 cm^-1. FAB-MS: m/z = 398 [M⁺], 351, 323, 317, 279, 244, 207, 154, 136, 117, 107, 90, 78, 70, 56.