Indium Tribromide Catalyzed Highly Regioselective Ring Opening of
Epoxides and Aziridines with Pyrrole

Abstract

Pyrrole reacts smoothly with terminal epoxides in the presence of a catalytic amount of InBr₃ under very mild conditions to afford the corresponding C-alkylated pyrroles in high yields. Similarly, activated aziridines also opened by pyrrole under the influence of indium tribromide to afford 2- and 3-alkyl pyrrole derivatives in high yields with high regioselectivity.

indium reagents - epoxides - C-alkylation - pyrrole

References

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9

Experimental Procedure: A mixture of epoxide or aziridine (5 mmol), pyrrole (5 mmol) and InBr₃ (10 mol%) in CH₂Cl₂ (10 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 H₂O (2 × 10 mL) and extracted with CH₂Cl₂ (2 × 15 mL). The combined organic layers were dried over anhyd Na₂SO₄, concentrated in vacuo and purified by column chromato-graphy on silica gel (Merck, 100-200 mesh, EtOAc-hexane 2:8) to afford pure product. The aq layer was concentrated in vacuo to recover the catalyst. Spectroscopic data for compounds:
2a: 2-(2-Pyrrolyl)-2-phenylethanol: ¹H NMR (200 MHz, CDCl₃): δ = 8.45 (brs, NH), 7.43-7.18 (m, 5 H), 6.65 (dd, 1 H, J = 2.8, 3.8 Hz), 6.15 (dd, 1 H, J = 2.8, 6.0 Hz), 5.95 (d, 1 H, J = 2.8 Hz), 3.98-4.20 (m, 3 H), 2.05 (brs, OH). MS (EI): m/z = 187 [M⁺]; IR(neat): ν = 3520, 3347, 1620, 1508 1243, 1048, 710 cm^-1.
3a: 2-(3-Pyrrolyl)-2-phenylethanol: ¹H NMR (200 MHz CDCl₃): δ = 8.15 (brs, NH), 7.38-7.20 (m, 5 H), 6.70 (d, 1 H, J = 2.5 Hz), 6.60 (m, 1 H), 6.10 (dd, 1 H, J = 2.5, 3.7 Hz), 3.97-4.18 (m, 3 H), 1.55 (brs, OH). MS (EI): m/z = 187 [M⁺]; IR(neat): ν = 3515, 3347, 1620, 1508, 1243, 1048, 710 cm^-1.
4o: 2-(2-(4-Methylphenylsulfonamido)-1-phenylethyl)-1 H -pyrrole: ¹H NMR (200 MHz, CDCl₃): δ = 7.90 (brs, NH), 7.65 (d, 2 H, J = 8.0 Hz), 7.38-7.20 (m, 5 H), 7.10 (d, 2 H, J = 8.0 Hz) 6.65 (dd, 1 H, J = 2.9, 3.7 Hz), 6.14 (dd, 1 H, J = 2.9, 6.0 Hz), 5.95 (d, 1 H, J = 2.9 Hz), 4.45 (t, 1 H, J = 6.5 Hz), 4.10 (t, 1 H, J = 7.0 Hz), 3.47 (ddd, 1 H, J = 6.5, 7.0, 12.8 Hz), 3.43 (ddd, 1 H, J = 7.0, 7.0, 12.8 Hz), 2.40 (s, 3 H). MS (EI): m/z = 340 [M⁺]; IR(neat): ν = 3375, 3283, 2925, 1714, 1594, 1421, 1312, 1125, 1086, 798, 712 cm^-1.
5o: 3-[2-(4-Methylphenylsulfonamido)-1-phenylethyl]-1 H -pyrrole: ¹H NMR (200 MHz, CDCl₃): δ = 8.15 (brs, NH), 7.65 (d, 2 H, J = 8.0 Hz), 7.30-7.20 (m, 5 H), 7.10 (d, 2 H, J = 8.0 Hz) 6.68 (d, 1 H, J = 2.5 Hz), 6.54 (m, 1 H), 5.97 (dd, 1 H, J = 2.5, 3.7 Hz), 4.38 (t, 1 H, J = 6.5 Hz), 3.98 (t, 1 H, J = 7.3 Hz), 3.38 (ddd, 2 H, J = 6.5, 7.3, 12.8 Hz), 3.43 (ddd, 1 H, J = 7.0, 7.0, 12.8 Hz), 2.40 (s, 3 H). MS (EI): m/z = 340 [M⁺]; IR(neat): ν = 3375, 3283, 2925, 1714, 1594, 1421, 1312, 1125, 1086, 798, 713 cm^-1.