Synthesis of β-Arylbutenolides Mediated by BF₃·OMe₂

Abstract

The reaction of phenols or aryl ethers with tetronic acid mediated by BF₃·OMe₂ was investigated. This strategy allowed for the preparation of β-(hydroxyaryl)butenolides and β-arylbutenolides in a single step in a simpler way than previously reported synthetic methods

Key words

butenolides - aromatic electrophilic substitution - rubrolides - synthons - tetronic acid

Publication History

Received: 26 August 2022

Accepted after revision: 07 October 2022

Article published online:
03 November 2022

• References and Notes

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• 20 Typical Experimental Procedure A mixture of tetronic acid (1.0 mmol), phenol (1.0 mmol) or aryl ether, and BF₃·OMe₂ (2.0 equiv) in CHCl₃ (3 mL) was taken in a reaction flask equipped with a small magnetic stirring bar and the reflux condenser. The mixture was irradiated in a microwave reactor at a power of 220 W. The reaction was monitored by TLC, and after the consumption of the starting materials, it was cooled to room temperature. The solvent was removed under vacuum, and the precipitated crude product was washed with a mixture of hexane-ethyl acetate (8:2). When sesamol was used as phenol, the mixture was maintained at room temperature under stirring for 24 h. The proceeding after the reaction was the same described above. 4-(2-Hydroxy-4,5-dimethoxyphenyl)furan-2(5H)-one (3a) 0.2149 g, 92%; mp 236–237 °C. ¹H NMR (400 MHz, DMSO-d ₆): δ = 10.3 (s, OH), 6.94 (s, 1 H), 6.46 (s, 1 H), 6.40 (s, 1 H), 5.21 (s, 2 H), 3.67 (s, 3 H), 3.64 (s, 3 H). ¹³C NMR (125 MHz, DMSO-d ₆): δ = 174.4, 162.6, 152.8, 152.7, 142.1, 111.3, 109.5, 107.5, 100.4, 72.4, 56.3, 55.4. HRMS (ESI⁺): m/z [M + H]⁺ calcd for C₁₂H₁₂O₅Na: 259.0581; found: 259.0572. 4-(6-Hydroxybenzo[d][1,3]dioxol-5-yl)furan-2(5H)-one (3b) 0.1885 g, 85%; mp 228–230 °C. ¹H NMR (400 MHz, DMSO-d ₆): δ = 10.63 (s, OH), 7.14 (s, 1 H), 6.54 (s, 1 H), 6.46 (s, 1 H), 6,03 (s, 2 H), 5.26 (s, 2 H). ¹³C NMR (125 MHz, DMSO-d ₆): δ = 174.4, 162.5, 154.0, 150.8, 140.7, 109.8, 108.3, 106.4, 101.7, 97.6, 72.5. HRMS (ESI⁺): m/z [M + H]⁺ calcd for C₁₁H₈O₅Na: 243.0268; found: 243.0263. 4-(2,4-Dihydroxyphenyl)furan-2(5H)-one (3c) 0.1825 g, 95%; mp 241–242 °C. ¹H NMR (400 MHz, DMSO-d ₆): δ = 10.56 (s, OH), 10.09 (s, OH), 7.34 (d, 1 H, J = 8.6 Hz), 6.40 (d, 1 H, J = 2.6 Hz), 6.37 (d, 1 H, J = 1.3 Hz), 6.33 (dd, 1 H, J = 2.2, 8.6 Hz), 5.26 (br s, 2 H). ¹³C NMR (125 MHz, DMSO-d ₆): δ = 174.6, 162.4, 161.6, 159.0, 130.0, 109.8, 108.8, 107.8, 102.6, 72.5. HRMS (ESI⁺): m/z [M + H]⁺ calcd for C₁₀H₈O₄Na: 215.0319; found: 215.0313. 4-(2,4-Dimethoxyphenyl)furan-2(5H)-one (3d) 0.2024 g 92%; mp 205–207 °C. ¹H NMR (400 MHz, DMSO-d ₆): δ = 7.52 (d, 1 H, J = 8.66 Hz), 6.69 (d, 1 H, J = 2.33 Hz), 6,64 (dd, 1 H, J = 8.65, 2.33 Hz), 6.50–6.46 (m, 1 H), 5.29 (d, 2 H, J = 1.55 Hz), 3.90 (s, 3 H), 3.84 (s, 3 H). ¹³C NMR (125 MHz, DMSO-d ₆): δ = 174.3, 163.3, 161.1, 160.0, 130.0, 111.2, 111.0, 106.2, 98.6, 72.1, 55.8, 55.6. HRMS (ESI⁺): m/z [M + Na]⁺ calcd for C₁₂H₁₂O₄Na: 243.0633; found: 243.0632.
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