Scandium Triflate Catalyzed Nazarov Cyclization of Arylvinyl Epoxides Derived from Alkoxides and Chloro(aryl)carbenes: A Facile Access to Resveratrol-Derived Natural Products

Abstract

The reaction of arylvinyl alkoxides with chloro(aryl)carbenes provided the corresponding arylvinyl epoxides that underwent Nazarov cyclization in a catalytic amount of scandium triflate, providing easy access to several highly substituted indenes, including some resveratrol-derived natural products.

Key words

Nazarov cyclization - arylvinyl alcohol - arylvinyl epoxides - indenes - resveratrol-derived natural products - scandium triflate - chloro(aryl)carbenes

• References and Notes

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• 16 Typical Procedure for the Synthesis of 2 To a mixed suspension of potassium hydride (2.5 equiv) and potassium tert-butoxide (2.5 equiv) in THF was added a THF (2.5 mL) solution of 8 (1.0 equiv), and the mixture was stirred at 0 °C under an argon atmosphere for 5 min after that was added a THF (2.5 mL) solution of benzal chloride (2.5 equiv). After completing the starting material, the reaction was quenched with aq NH₄Cl and extracted with EtOAc. The organic layer was washed with aq NaCl, dried over Na₂SO₄, and concentrated under reduced pressure. The crude product was purified by using basic Al₂O₃ column chromatography to isolate 2. Characterization Data of 2a 123.5 mg, 90% yield, dr 1:1 based on ¹H NMR spectroscopy. ¹H NMR (500 MHz, CDCl₃): δ = 7.25–7.14 (m, 5 H), 6.41 (d, J = 2.3 Hz, 2 H), 6.22 (t, J = 2.3 Hz, 1 H), 4.37 (s, 1 H), 3.66 (s, 6 H), 2.08 (s, 3 H), 1.76 (s, 3 H), 1.74 (s, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 160.0, 139.1, 135.3, 128.9, 128.7, 127.8, 127.5, 126.7, 105.8, 99.2, 69.6, 68.3, 55.2, 22.5, 20.3, 15.0. IR (neat): ν_max = 2927, 1594, 1454, 1425, 1345, 1202, 1152, 1063, 842, 737, 697. HRMS (ESI): m/z calcd for C₂₁H₂₅O₃ [M + H]: 325.1798; found: 325.1791. Typical Procedure for the Synthesis of 3 To a stirred solution of above-obtained 2 (1.0 equiv) in dry CH₂Cl₂ (3.7 mL) was added Sc(OTf)₃ (0.1 equiv) at 0 °C, and stirring was continued at the same temperature. After completing the starting material, the reaction was quenched with water or saturated aq NaHCO₃ solution and extracted with CH₂Cl₂. The organic layer was washed with aq NaCl solution, dried over Na₂SO₄, filtered, and concentrated under reduced pressure. The crude product was purified by using silica gel column chromatography (EtOAc/hexanes) to give 3. Characterization Data of 3a 118 mg, 96% yield. ¹H NMR (400 MHz, CDCl₃): δ = 7.44 (d, J = 7.6 Hz, 2 H), 7.3 (t, J = 7.6 Hz, 2 H), 7.2 (t, J = 7.6 Hz, 1 H), 6.34 (d, J = 2.0 Hz, 1 H), 6.15 (d, J = 2.0 Hz, 1 H), 5.93 (s, 1 H), 3.73 (s, 3 H), 3.58 (s, 3 H), 2.1 (br s, 1 H), 1.92 (s, 3 H), 1.32 (s, 3 H), 1.30 (s, 3 H). ¹³C NMR (125 MHz, CDCl₃): δ = 159.9, 155.7, 153.2, 143.2, 142.4, 134.2, 131.5, 128.3, 126.9, 125.7, 98.5, 95.2, 69.4, 55.4, 55.1, 50.3, 21.8, 21.2, 9.9. IR (neat): ν_max = 3395, 2956, 2925, 2855, 1595, 1454, 1349, 1203, 1152, 1090, 699. HRMS (ESI): m/z calcd for C₂₁H₂₃O₂ [M – OH]: 307.1698; found: 307.1692.
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