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.

indium reagents - epoxides - indoles - tryptophol derivatives

References

1a Parker RE. Isaacs NS. Chem. Rev.  1959,  59:  737 

1b Bonini C. Righi G. Synthesis  1994,  225 

2a Rao AS. Paknikar SK. Kirtane JG. Tetrahedron  1983,  39:  2323 

2b Smith JG. Synthesis  1984,  629 

2c Hirose T. Sunazuka T. Zhi-ming T. Handa M. Vchida R. Shiomi K. Harigaya Y. Omura S. Heterocycles  2000,  53:  777 

3 Kotsuki H. Teraguchi M. Shimomoto N. Ochi M. Tetrahedron Lett.  1996,  37:  3727 

4a Kotsuki H. Hayashida K. Shimanouchi T. Nishizawa H. J. Org. Chem.  1996,  61:  984 

4b Kotsuki H. Nishiuchi M. Kobayashi S. Nishizawa H. J. Org. Chem.  1990,  55:  2969 

5 Dirlam JP. Clark DA. Hecker SJ. J. Org. Chem.  1986,  51:  4920 

6a Li CJ. Chan TH. Tetrahedron  1999,  55:  11149 

6b Babu G. Perumal PT. Aldrichimica Acta  2000,  33:  16 

6c Ghosh R. Indian J. Chem.  2001,  40B:  550 

7a Yadav JS. Reddy BVS. Kumar GM. Synlett  2001,  1417 

7b Yadav JS. Sunny A. Reddy BVS. Sabitha G. Synthesis  2001,  2165 

7c Yadav JS. Sunny A. Reddy BVS. Sabitha G. Tetrahedron Lett.  2001,  42:  8063 

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.