Synthesis of Tetracyclic Flavonoids via Palladium-Catalyzed Intramolecular Oxidative Cyclization

Dedicated to Professors Charles J. Kelley and Scott D. Rychnovsky

Abstract

Palladium-catalyzed oxidative cyclization of terminal-olefin-tethered phenols was achieved in good yields (61–90% yields). The reaction was optimized and White catalyst {[1,2-bis-(phenylsulfinyl)ethane]palladium(II)acetate} provided the best yield in the presence of benzoquinone as an oxidant. The reaction tolerated both electron-donating and electron-withdrawing substituents on the substrates, and the structure of the tetracyclic flavonoids was confirmed using single-crystal X-ray analysis. The study represents the first example of successful allylic C–H activation/ C–O bond formation using terminal-olefin-tethered phenols.

Key words

allylic C–H activation - palladium - phenol - flavonoids - C–O bond formation

• References and Notes

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• 13 General Procedure for Compound 7f A dry two-neck round-bottom flask was charged with White catalyst (0.027 g, 0.053 mmol, 0.2 equiv) and benzoquinone (0.059 g, 0.55 mmol, 2 equiv). Compound 6f (0.09 g, 0.27 mmol, 1 equiv) and AcOH (0.018 g, 0.29 mmol, 1.1 equiv) in CH₂Cl₂ (5 mL) was added dropwise to the above mixture and refluxed for 5 h. To the reaction mixture, sat. NH₄Cl was added, and the mixture was extracted with CH₂Cl₂. The organic phase was washed with brine, dried over Na₂SO₄, and evaporated. The crude product was purified by silica gel column chromatography by eluting with EtOAc–hexanes (5%) to afford 7f (79 mg, 87%). Spectral Data White solid; yield 79 mg (87%); mp 171–172 °C. IR (KBr): 3020 (w), 1635 (s), 1612 (s), 1216 (s), 832 (m), 772 (s) cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 2.51 (s, 3 H), 5.16 (dt, J = 10.4, 1.3 Hz, 1 H), 5.34 (dt, J = 17.1, 1.2 Hz, 1 H), 5.99 (ddd, J = 17.1, 10.5, 5.0 Hz, 1 H), 6.15 (dt, J = 5.0, 1.5 Hz, 1 H), 7.01 (dd, J = 8.3, 0.7 Hz, 1 H), 7.07 (td, J = 7.6, 1.0 Hz, 1 H), 7.41 (ddd, J = 8.3, 7.4, 1.7 Hz, 1 H), 7.44 (s, 1 H), 7.78 (dd, J = 7.8, 1.5 Hz, 1 H), 8.16 (s, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 20.8, 72.9, 111.9, 115.6, 117.0, 117.7, 119.9, 121.7, 123.2, 123.7, 125.5, 131.9, 134.0 (2×), 142.9, 153.9, 154.9, 156.1, 173.5. ESI-MS: m/z = 325.1 [M + H]⁺.
• 14 CCDC 1017874.