One-Pot Synthesis of Novel Highly Functionalized Furan-Based Polyphenolics

Abstract

Novel, highly functionalized furan-based polyphenolics were prepared. The employed methodology involves a one-pot 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) catalyzed 1,4-conjugate addition of 1,3-dicarbonyl compounds on 3-bromochromones, furan heterocyclization, and chromanone ring opening.

Key words

furan - polyphenols - 1,3-dicarbonyl compounds - 1,4-conjugate addition - ring transformation

• References and Notes

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• 15 Synthesis of Furan-Based Polyphenolics 3a–i; General Procedure: 3-Bromo-4H-chromen-4-ones 1a,b and 1,3-dicarbonyl compounds 2b–h were prepared by following previously reported methods.^14,19 3-Bromochromone 1a,b (1.0 mmol) and 1,3-dicarbonyl compound 2a–h (1.1 mmol) were dissolved in THF (40 mL). DBU (1 drop per 50 mg of starting material) was then added and the resulting reaction mixture was stirred vigorously and heated to reflux. After 48 h, the solvent was evaporated under reduced pressure and the residue was purified by short plug silica gel column chromatography using dichloromethane as eluent. The purified products 3a–i were recrystallized from hexane/dichloromethane (1:1) by slow evaporation at 6 °C.
• 16 Typical Analytical Data: (4-Acetyl-5-methylfuran-2-yl)(2-hydroxyphenyl)methanone (3a): Yield: 171 mg (70%); yellow crystals; mp 99–100 °C (Lit.¹³ mp 98–100 °C). ¹H NMR (300.13 MHz, CDCl₃): δ = 11.94 (s, 1 H, 3′-OH), 8.19 (dd, J = 8.2, 1.6 Hz, 1 H, H-7′), 7.58 (s, 1 H, H-3), 7.54 (ddd, J = 8.5, 7.3, 1.6 Hz, 1 H, H-5′), 7.06 (dd, J = 8.5, 1.1 Hz, 1 H, H-4′), 6.99 (ddd, J = 8.2, 7.3, 1.1 Hz, 1 H, H-6′), 2.77 (s, 1 H, 5-CH₃), 2.50 (s, 1 H, 2′′-CH₃). ¹³C NMR (75.47 MHz, CDCl₃): δ = 193.2 (C-1′′), 184.4 (C-1′), 163.3 (C-3′), 163.2 (C-5), 149.2 (C-2), 136.4 (C-5′), 131.1 (C-7′), 123.4 (C-4), 121.1 (C-3), 119.2 (C-6′), 118.6 (C-4′), 118.5 (C-2′), 29.1 (2′′-CH₃), 15.1 (5-CH₃). HRMS (ESI⁺): m/z calcd for [C₁₄H₁₂O₄+H]⁺: 245.0808; found: 245.0821. (E)-[4-(2-Hydroxy-4-methoxybenzoyl)-5-(3,4-dimethoxystyryl)furan-2-yl](2-hydroxyphenyl)methanone (3b): Yield: 240 mg (48%); orange solid; mp 134–135 °C. ¹H NMR (500.13 MHz, CDCl₃): δ = 12.59 (s, 1 H, 3′′-OH), 11.95 (s, 1 H, 3′-OH), 8.22 (dd, J = 8.2, 1.6 Hz, 1 H, H-7′), 7.64 (d, J = 9.0 Hz, 1 H, H-7′′), 7.59 (s, 1 H, H-3), 7.57 (d, J = 16.5 Hz, 1 H, H-β), 7.56 (ddd, J = 8.4, 7.2, 1.6 Hz, 1 H, H-5′), 7.22 (d, J = 16.5 Hz, 1 H, H-α), 7.16 (dd, J = 8.4, 1.9 Hz, 1 H, H-6′′′), 7.10 (dd, J = 8.4, 1.0 Hz, 1 H, H-4′), 7.08 (d, J = 1.9 Hz, 1 H, H-2′′′), 7.02 (ddd, J = 8.2, 7.2, 1.0 Hz, 1 H, H-6′), 6.89 (d, J = 8.4 Hz, 1 H, H-5′′′), 6.54 (d, J = 2.5 Hz, 1 H, H-4′′), 6.49 (dd, J = 9.0, 2.5 Hz, 1 H, H-6′′), 3.95 (s, 3 H, 3′′′-OCH₃), 3.93 (s, 3 H, 4′′′-OCH₃), 3.89 (s, 3 H, 5′′-OCH₃). ¹³C NMR (125.77 MHz, CDCl₃): δ = 191.9 (C-1′′), 184.3 (C-1′), 166.6 (C-5′′), 166.2 (C-3′′), 163.3 (C-3′), 159.6 (C-5), 150.8 (C-4′′′), 149.3 (C-3′′′), 148.9 (C-2), 136.6 (C-β), 136.4 (C-5′), 133.7 (C-7′′), 131.0 (C-7′), 128.6 (C-1′′′), 123.0 (C-3), 122.0 (C-6′′′), 121.9 (C-4), 119.3 (C-6′), 118.8 (C-2′), 118.7 (C-4′), 114.0 (C-2′′), 112.1 (C-α), 111.2 (C-5′′′), 109.3 (C-2′′′), 108.0 (C-6′′), 101.3 (C-4′′), 56.02, 56.00 (3′′′, 4′′′-OCH₃), 55.77 (5′′-OCH₃). HRMS (ESI⁺): m/z calcd for [C₂₉H₂₄O₈+Na]⁺: 523.1363; found: 523.1344. (E)-[5-(4-Chlorostyryl)furan-2,4-diyl]bis[(2-hydroxyphenyl)-methanone] (3c): Yield: 249 mg (56%); yellow solid; mp 193–194 °C. ¹H NMR (300.13 MHz, CDCl₃): δ = 11.90 (s, 1 H, 3′-OH), 11.86 (s, 1 H, 3′′-OH), 8.21 (dd, J = 8.2, 1.5 Hz, 1 H, H-7′), 7.72 (dd, J = 8.1, 1.6 Hz, 1 H, H-7′′), 7.61 (s, 1 H, H-3), 7.60–7.49 (m, 4 H, H-5′,5′′, H-3′′′,5′′′), 7.53 (d, J = 16.3 Hz, 1 H, H-β), 7.38 (d, J = 8.6 Hz, 2 H, H-2′′′,6′′′), 7.37 (d, J = 16.3 Hz, 1 H, H-α), 7.12–7.09 (m, 2 H, H-4′,4′′), 7.03 (ddd, J = 8.1, 7.2, 1.2 Hz, 1 H, H-6′′), 6.96 (ddd, J = 8.2, 7.3, 1.1 Hz, 1 H, H-6′). ¹³C NMR (75.47 MHz, CDCl₃): δ = 193.5 (C-1′′), 184.4 (C-1′), 163.4 (C-3′), 163.0 (C-3′′), 159.2 (C-5), 149.3 (C-2), 137.0 (C-5′′), 136.6 (C-5′), 135.6 (C-1′′′), 135.5 (C-β), 133.9 (C-4′′′), 131.9 (C-7′′), 131.0 (C-7′), 129.3 (C-2′′′,6′′′), 128.8 (C-3′′′,5′′′), 122.7 (C-3), 122.5 (C-4), 119.9 (C-2′′), 119.4 (C-6′), 119.3 (C-6′′), 118.8 (C-4′,4′′), 118.7 (C-2′), 114.5 (C-α). HRMS (ESI⁺): m/z calcd for [C₂₆H₁₇O₅Cl+H]⁺: 445.0837; found: 445.0833.
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