A New Preparative Route to Substituted Dibenzofurans by Benzannulation Reaction. An Application to the Synthesis of Cannabifuran

Abstract

A new regioselective pathway to substituted dibenzo­furan derivatives is described here. According to this procedure substituted 1-acetoxy-3-alkoxycarbonyl dibenzofurans are obtained by treatment of 6-(2-methoxyaryl)-3-alkoxycarbonylhex-3-en-5-ynoic acids with acetic anhydride in the presence of sodium acetate. The latter acids are prepared from the easily available substituted o-iodo-anisoles by Sonogashira coupling with propargylic alcohol and Wittig reaction as the key steps. The described benzannulation reaction proceeds in regioselective fashion and a range of sub­stituents are tolerated. Its synthetic utility is demonstrated by a new synthesis of cannabifuran, a naturally occurring dibenzofuran.

annulations - enynes - benzofurans - phenols - natural products

References

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All new compounds were fully characterized. Selected analytical data:
12: Anal. Calcd for C₁₄H₁₈O₂: C, 77.03; H, 8.31. Found: C, 77.15; H, 8.35. Bp 150 °C/0.5 mmHg. ¹H NMR (250 MHz, CDCl₃): δ = 1.22 (6 H, d, J = 6.9 Hz), 2.23 (3 H, s), 2.50-2.85 (1 H, bs), 3.38 (1 H, m), 3.86 (3 H, s), 4.58 (2 H, s), 6.93 (1 H, d, J = 8.0 Hz), 7.10 (1 H, d, J = 8.0 Hz). EI-MS: m/z = 219 (M⁺ + 1), 218 (M⁺), 203, 187, 172, 159, 141, 128, 115, 105, 91, 77. FT-IR (film): ν = 813, 1029, 1077, 1237, 1273, 1405, 1459, 1481, 1571, 2225, 2929, 3407 cm^-1.
13: Anal. Calcd for C₂₀H₂₄O₅: C, 69.75; H, 7.02. Found: C, 69.60; H, 7.10. Mp 59-60 °C (hexane). ¹H NMR (250 MHz, CDCl₃): δ = 1.22 (6 H, d, J = 6.9 Hz), 1.31 (3 H, t, J = 7.1 Hz), 2.24 (3 H, s), 3.34 (1 H, m), 3.77 (2 H, s), 3.83 (3 H, s), 4.26 (2 H, q, J = 7.1 Hz), 6.95 (1 H, d, J = 8.0 Hz), 7.15 (1 H, d, J = 8.0 Hz), 7.15 (1 H, s). EI-MS: m/z = 345 (M⁺ + 1), 344 (M⁺), 316, 300, 285, 270, 255, 239, 225, 209, 195, 173, 165, 152, 128, 115, 97. FT-IR (nujol): ν = 762, 1031, 1093, 1212, 1265, 1376, 1459, 1619, 1699, 1719, 2193 cm^-1.
14: Anal. Calcd for C₂₁H₂₂O₅: C, 71.17; H, 6.26. Found: C, 71.10; H, 6.25. Mp 113-114 °C (isopropyl ether). ¹H NMR (250 MHz, CDCl₃): δ = 1.36 (6 H, d, J = 6.9 Hz), 1.42 (3 H, t, J = 7.2 Hz), 2.45 (3 H, s), 2.54 (3 H, s), 3.99 (1 H, m), 4.42 (2 H, q, J = 7.2 Hz), 7.19 (1 H, d, J = 7.7 Hz), 7.30 (1 H, d, J = 7.7 Hz), 7.75 (1 H, d, J = 1.2 Hz), 8.16 (1 H, d, J = 1.2 Hz). EI-MS: m/z = 355 (M⁺ + 1), 354 (M⁺), 312, 297, 283, 267, 255, 239, 224, 205, 195, 178, 165, 152, 139, 128, 115, 102, 89. FT-IR(nujol): ν = 770, 1065, 1195, 1229, 1310, 1368, 1411, 1463, 1510, 1571, 1712, 1771 cm^-1.
Cannabifuran 15: Anal. Calcd for C₂₁H₂₆O₂: C, 81.25; H, 8.44. Found: C, 81.00; H, 8.45. Mp 79-80 °C (hexane). ¹H NMR (250 MHz, CDCl₃): δ = 0.89 (3 H, t, J = 6.6 Hz), 1.34 (6 H, d, J = 6.8 Hz), 1.20-1.46 (4 H, m), 1.55-1.81 (2 H, m), 2.53 (3 H, s), 2.66 (2 H, t, J = 7.5 Hz), 4.41 (1 H, m), 5.55
(1 H, bs), 6.46 (1 H, s), 7.01 (1 H, s), 7.17 (2 H, m). EI-MS: m/z = 311 (M⁺ + 1), 310 (M⁺), 295, 281, 267, 254, 238, 225, 211, 191, 178, 165, 152, 139, 119, 105, 89. FT-IR (nujol):
ν = 760, 815, 1048, 1061, 1219, 1252, 1426, 1514, 1588, 1618, 1635, 3500 cm^-1.

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