A Novel Approach for the Synthesis of Dipyrrolyl Alkanols and Dipyrrolyl Alkylamines

Abstract

Pyrrole reacts smoothly with cyclic enol ethers and enecarbamates in the presence of 5 mol% indium tribromide or 10 mol% indium trichloride under mild and convenient conditions to afford the corresponding bis-pyrrolyl-alkanols and alkyl amines, respectively, in high yields with high selectivity.

Key words

enol ethers - enecarbamates - pyrrole - indium reagents - bis-pyrrolyl alkanes

References

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9

Enantiomeric purity of the product 6n (94%) was determined by Chiral HPLC using Chiralcel OJ column; mobile phase 10% isopropanol in n-hexane; flow rate 0.5 mL/min. This clearly indicates that the product 6n was obtained without any racemization under the reaction conditions.

10

General Procedure: A mixture of pyrrole (4 mmol) and enol ether or enecarbamates (2 mmol) and indium tribromide (5 mol%) or indium trichloride (10 mol%) in MeCN (10 mL, Analytical Reagent Grade) was stirred under N₂ atmosphere at r.t. for 4.5-9.5 h. After complete conversion, as indicated by TLC, the reaction mixture was diluted with H₂O (10 mL) and extracted with CH₂Cl₂ (2 × 15 mL). The organic layers were dried over anhyd Na₂SO₄ and purified by column chromatography on silica gel (Merck, 100-200 mesh, ethyl acetate-hexane, 2:8) to afford pure dipyrrolyl alkyl derivative. The aq layer was concentrated in vacuo to recover the catalyst. Spectroscopic data for selected products: 2a: Liquid. ¹H NMR (200 MHz, CDCl₃): δ = 1.40-1.65 (m, 2 H), 1.90-2.05 (m, 2 H), 3.65 (t, 2 H, J = 6.5 Hz), 4.05 (t, 1 H, J = 6.5 Hz), 6.05 (d, 2 H, J = 2.0 Hz), 6.10 (dd, 2 H, J = 2.0, 2.5 Hz), 6.60 (d, 2 H, J = 2.5 Hz), 7.80 (br s, NH, 2 H). IR (KBr): ν = 3450, 3370, 1598, 1445, 1380, 1296, 1226, 1141, 1090, 751 cm^-1. MS (EI): m/z = 204 [M⁺], 186, 155, 141, 128, 77, 81, 51.
3d: Liquid. ¹H NMR (200 MHz, CDCl₃): δ = 1.40-1.70 (m, 3 H), 1.80-2.0 (m, 3 H), 3.45 (dd, 1 H, J = 6.5, 10.3 Hz), 3.90 (d, 1 H, J = 10.3 Hz), 4.10 (t, 1 H, J = 6.5 Hz), 5.10 (q, 2 H, J = 16.5 Hz), 6.0-6.10 (m, 2 H), 6.60 (d, 1 H, J = 2.0 Hz), 7.05 (d, 2 H, J = 8.0 Hz), 7.20-7.40 (m, 3 H). IR (KBr): ν = 3065, 1710, 1568, 1440, 1385, 1299, 1225, 1140, 1090, 750 cm^-1. MS (EI): m/z = 241 [M⁺], 183, 168, 141, 91, 65, 41.
3e: Liquid. ¹H NMR (200 MHz, CDCl₃): δ = 1.60 (s, 9 H), 1.80-2.0 (m, 3 H), 2.20-2.40 (m, 1 H), 3.80-3.85 (m, 1 H), 3.97-4.10 (m, 1 H), 5.38-5.05 (m, 1 H), 6.05 (dd, 1 H, J = 2.0, 2.5 Hz), 6.20 (d, 1 H, J = 2.0 Hz), 7.25 (d, 1 H, J = 2.5 Hz). IR (KBr): ν = 3029, 1575, 1445, 1380, 1297, 1226, 1143, 1091, 752 cm^-1. MS (EI): m/z = 237 [M⁺], 196, 151, 136, 123, 103, 95, 81, 65. 5i: Liquid. ¹H NMR (200 MHz, CDCl₃): δ = 1.40 (s, 9 H), 1.80-2.0 (m, 2 H), 3.0-3.10 (m, 2 H), 3.85 (t, 1 H, J = 7.0 Hz), 4.40 (br s, 1 H, NH), 5.90 (d, 2 H, J = 2.0 Hz), 6.10 (dd, 2 H, J = 1.9, 2.3 Hz), 6.50 (d, 2 H, J = 2.3 Hz), 7.90 (br s, NH, 2 H). IR (KBr): ν = 3385, 3089, 1705, 1620, 1416, 1295, 1108, 963, 777 cm^-1. Mass (FAB): m/z = 303 [M⁺], 260, 246, 237, 202, 181, 154, 145, 137, 120, 81, 39.