Boron Trifluoride Etherate-Controlled Reactions of Methyl Enol Ethers: Selective Synthesis of Dihydrofuro[3,2-c]chromenone and Furo[3,2-c]chromenone Derivatives

Abstract

A facile one-step synthetic approach to dihydrofuro-[3,2-c]chromenones and furo[3,2-c]chromenones by the reaction of methyl enol ethers with 4-hydroxycoumarins under metal-free conditions is presented. Dihydrofuro[3,2-c]chromenones and furo[3,2-c]-chromenones were selectively obtained by controlling the stoichiometry of boron trifluoride diethyl etherate. An unexpected aryl-group migration followed by aromatization of the furan moiety, leading to a variety of furo[3,2-c]chromenone derivatives in good yields, is reported.

Keywords

methyl enol ethers - furochromenones - Lewis acids - aryl-group migration - tandem reaction - hydroxycoumarin

Publication History

Received: 30 May 2022

Accepted after revision: 28 July 2022

Accepted Manuscript online:
28 July 2022

Article published online:
14 October 2022

• References and Notes

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• 17 Dihydrofuro[3,2-c]chromenones (3a–l); General Procedure A screw-capped reaction tube was charged with the appropriate methyl enol ether 1 (0.25 mmol, 1 equiv) and 4-hydroxycoumarin 2 (0.25 mmol, 1 equiv) in anhyd MeNO₂ (3 mL). BF₃·Et₂O (0.25 mmol, 1 equiv) was added, and the mixture was stirred at 90 °C. When 1 was completely consumed (TLC), the mixture was diluted with H₂O (15 mL) and the organic layer was extracted by EtOAc (3 × 20 mL). The extracts were washed with brine, dried (Na₂SO₄), and concentrated on a rotary evaporator to give a residue that was purified by flash chromatography (silica gel, hexane–EtOAc). 2-Methyl-2-phenyl-2,3-dihydro-4H-furo[3,2-c]chromen-4-one (3b) Yellow solid; yield: 84%; mp 99–101 °C. ¹H NMR (400 MHz, CDCl₃): δ = 7.70 (dd, J = 7.8, 1.5 Hz, 1 H), 7.53–7.45 (m, 1 H), 7.37 (dd, J = 5.5, 3.4 Hz, 2 H), 7.34–7.27 (m, 3 H), 7.26–7.20 (m, 2 H), 3.30 (dd, J = 34.0, 15.1 Hz, 2 H), 1.81 (s, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 165.4, 160.7, 155.1, 144.7, 132.4, 128.7, 127.9, 124.2, 124.0, 122.8, 117.0, 112.7, 101.5, 94.8, 41.6, 29.5. HRMS (ESI-TOF): m/z [M + H]⁺ calcd for C₁₈H₁₅O₃: 279.1016; found: 279.1000.
• 18 Furo[3,2-c]chromenones 4a–j; General Procedure A screw-capped reaction tube was charged with the appropriate methyl enol ether 1 (0.25 mmol, 1 equiv) and 4-hydroxy 2 (0.25 mmol, 1 equiv) in dry MeNO₂ (3 mL); BF₃·Et₂O (0.62 mmol, 2.5 equiv) was added, and the mixture was stirred at 90 °C. When 1 was completely consumed (TLC), the mixture was worked up as described above. 2,3-Bis(4-methylphenyl)-4H-furo[3,2-c]chromen-4-one White solid; yield: 87%; mp 190–192 °C. ¹H NMR (400 MHz, CDCl₃): δ = 7.97 (dd, J = 7.8, 1.4 Hz, 1 H), 7.53–7.48 (m, 1 H), 7.46–7.43 (m, 3 H), 7.40–7.36 (m, 3 H), 7.24 (d, J = 8.2 Hz, 2 H), 7.13 (d, J = 8.1 Hz, 2 H), 2.42 (s, 3 H), 2.35 (s, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 157.7, 156.2, 152.6, 151.5, 138.9, 138.1, 130.5, 130.1, 129.7, 129.3, 129.3, 127.2, 126.6, 124.4, 120.9, 120.2, 117.2, 112.8, 111.4, 21.5, 21.4. HRMS (ESI-TOF): m/z [M + Na]⁺ calcd for C₂₅H₁₈NaO₃: 389.1148; found: 389.1092.
• 19 CCDC 2163920 and 2161897 contain the supplementary crystallographic data for compounds 3b and 4f. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre www.ccdc.cam.ac.uk/structures