Palladium-Catalyzed Double Substitution of 3-Aryl-2-fluoroallyl Acetates with Phenols via C–F Bond Activation

Abstract

The double substitution of 3-aryl-2-fluoroallyl acetates with phenols has been accomplished; the Pd(PPh₃)₄ catalyst system has effectively catalyzed the reaction to afford the doubly substituted product via carbon–fluorine bond activation.

Key words

palladium - catalysis - fluorine - phenols - coupling

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For examples of platinum-catalyzed reaction, see:
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• 9 Double Substitution Reaction of 3-Aryl-2-fluoroallyl Acetates 1 with Phenols 2 – Typical Procedure A solution of (Z)-2-fluoro-3-phenylallyl acetate (1a, 25 mg, 0.13 mmol), phenol (2a, 36 mg, 0.39 mmol), Pd(PPh₃)₄ (15 mg, 0.013 mmol), and Cs₂CO₃ (118 mg, 0.361 mmol) in anhydrous toluene (0.6 mL) was stirred at 100 °C for 12 h. The reaction mixture was quenched with 2 N HCl (0.3 mL) and extracted with EtOAc (3 × 2 mL). The combined organic layers were dried over MgSO₄ and concentrated in vacuo. The NMR yield (95%, trioxane as an internal standard), and the ratio of (Z)-3aa to (E)-3aa was determined by 600 MHz ¹H NMR spectroscopy for the crude material. The residue was chromatographed on silica gel (hexane–EtOAc = 9:1) to give 35 mg (90%) of 3aa as a white solid; mp 105–109 °C. ¹H NMR (500 MHz, CDCl₃): δ = 4.58 (s, 2 H), 6.35 (s, 1 H), 6.89–6.96 (m, 3 H), 7.01–7.08 (m, 3 H), 7.18 (m, 1 H), 7.20–7.29 (m, 6 H), 7.58 (d, J = 6.9 Hz, 2 H). Selected ¹H NMR of minor isomer (E)-3aa: δ = 4.75 (s, 2 H), 6.15 (s, 1 H), aromatic region overlaps with major isomer. ¹³C NMR (125 MHz, CDCl₃): δ = 66.9, 114.9, 117.0, 117.6, 121.3, 122.9, 127.5, 128.4, 128.8, 129.4, 129.7, 133.9, 146.9, 155.3, 158.2. IR (KBr): 3089, 3053, 3023, 2927, 2861, 1683, 1588, 1488, 1338, 1162, 1062, 937, 757, 693, 514 cm^–1. ESI-HRMS: m/z calcd for [M + Na]⁺ C₂₁H₁₈NaO₂: 325.1204; found: 325.1197.
• 10 (Z)-3aa: CCDC number 995982.
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