InCl₃-Catalyzed Alkylation of Indoles with Epoxides

Abstract

Indoles react smoothly with terminal epoxides in the presence of catalytic amount of InCl₃ under mild conditions to afford the corresponding 3-alkyl indole derivatives in high yields with high regioselectivity.

Key words

indium reagents - epoxides - indoles - tryptophol derivatives

References

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8

Experimental procedure: A mixture of epoxide (5 mmol), indole (5 mmol) and InCl₃ (10 mol%) in dichloromethane (15 mL) was stirred at ambient temperature for an appropriate time (Table). After completion of the reaction, as indicated by TLC, the reaction mixture was diluted with water (2 × 10 mL) and extracted with dichloromethane (2 × 15 mL). The aqueous layer was concentrated in vacuo to recover the catalyst. The combined organic layers were dried over anhydrous Na₂SO₄, concentrated in vacuo and purified by column chromatography on silica gel (Merck, 100-200 mesh, ethyl acetate-hexane 2:8) to afford pure product. Spectral data for selected compounds 3a : Solid, mp 121-122 °C; IR (KBr): 3520, 3050, 1640, 1500, 1240, 700 cm^-1; ¹H NMR (200 MHz, CDCl₃): δ 2.13 (br s, 1 H, OH), 4.10 (dd, J = 10.5, 6.7 Hz, 1 H), 4.20 (dd, J = 10.5, 6.7 Hz, 1 H), 4.45 (t, 1 H, J = 6.7 Hz), 7.03 (dd, J = 8.0, 1.8 Hz, 1 H), 7.07 (d, J = 1.8 Hz, 1 H), 7.16 (dd, J = 8.0, 1.8 Hz, 1 H), 7.21 (m, 1 H), 7.26-7.36 (m, 5 H), 7.44 (d, J = 8.0 Hz, 1 H), 8.05 (brs, NH, 1 H); EIMS m/z: 237 (M⁺); Anal. Calcd for C₁₆H₁₅NO (237.30): C, 80.98; H, 6.37; N, 5.90. Found: C, 80.95; H, 6.44; N, 5.95.
4f : Solid, mp 83-84 °C; IR (KBr): 3420, 2980, 1597, 1481,1240, 770 cm^-1; ¹H NMR (200 MHz, CDCl₃): δ 2.35 (br s, 1 H, OH), 3.10 (d, J = 6.4 Hz, 2 H), 3.90 (dd, J = 13.5, 6.2 Hz, 1 H), 3.97 (dd, J = 13.5, 4.0 Hz, 1 H), 4.30 (m, 1 H), 6.80-7.35 (m, 9 H), 7.60 (d, J = 8.1 Hz, 1 H), 8.10 (br s, 1 H, NH); EIMS m/z: 267 (M⁺); Anal. Calcd for C₁₇H₁₇NO₂ (267.32): C, 76.38; H, 6.41; N, 5.24. Found: C, 76.41; H, 6.43; N, 5.30.