Palladium-Catalyzed Ring-Opening Coupling of Cyclobutenols with Aryl Halides

Published as part of the Cluster C–C Activation

Abstract

A palladium(0)-catalyzed ring-opening cross-coupling reaction between tert-cyclobutenols and aryl halides produces γ-arylated β,γ-unsaturated ketones. In the case of aryl halides bearing functional groups at the ortho position, the resulting ring-opened ketones undergo intramolecular condensation to afford bicyclic aromatic compounds.

Key words

palladium - cyclobutenols - arylation - ring opening - ketones - cross-coupling - condensation - homogeneous catalysis

• References and Notes


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For palladium(0)-catalyzed ring-opening arylation reactions of cyclobutanols, see:
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• 6 Abbreviations: dba = dibenzylideneacetone; DavePhos = 2-di-cyclohexylphosphino-2′-(N,N-dimethylamino)biphenyl; XPhos = 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl.

The site selectivity might be attributed to stabilization by an interaction between palladium(II) and the C=C bond. See:
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Pd–C(sp²) bond is stronger than Pd–C(sp³) bond by 8.7 kcal/mol, see:
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Silver(I) ion abstracts a halide ion to facilitate the generation of a cationic palladium(II) species, see:
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• 10 General Procedure for Palladium(0)-Catalyzed Ring-Opening Cross-Coupling of tert-Cyclobutenols 1 with Organohalides 2 (GP-1) A mixture of Pd₂(dba)₃ (2.3 mg, 2.5 μmol), XPhos (4.7 mg, 9.9 μmol), cyclobutenol 1 (0.120 mmol), organohalide 2 (0.100 mmol), and Ag₂CO₃ (30.3 mg, 0.11 mmol) in toluene (0.50 mL) was heated at 65 °C with stirring. The reaction mixture was filtered through a plug of Florisil^® washing with hexane/AcOEt (3:1), and the filtrate was concentrated. The residue was purified by preparative TLC on silica gel to afford ring-opened enone 3.
• 11 Selected Data for Products
  (E)-1-(4-Methylphenyl)-2-phenyl-1-octen-4-one (3a) The general procedure (GP-1) was followed using 1a (24.3 mg, 0.120 mmol) and 2a (17.1 mg, 0.100 mmol) for 6 h. Purification by preparative TLC on silica gel (hexane/AcOEt/toluene = 60:2:1, 4×) yielded 3a (22.1 mg, 0.076 mmol, 76%) as a yellow oil. The Z isomer (1.0 mg, 0.003 mmol, 3%) and (E)-2-phenyl-2-octen-4-one (4, 2.1 mg, 0.010 mmol, 9%) were also isolated. ¹H NMR (500 MHz, CDCl₃): δ = 0.83 (t, J = 7.3 Hz, 3 H), 1.21 (sext, J = 7.5 Hz, 2 H), 1.44–1.51 (m, 2 H), 2.38 (t, J = 7.5 Hz, 2 H), 2.37 (s, 3 H), 3.78 (s, 2 H), 7.01 (s, 1 H), 7.15–7.22 (m, 4 H), 7.26–7.30 (m, 1 H), 7.33–7.38 (m, 2 H), 7.42–7.46 (m, 2 H). ¹³C NMR (126 MHz, CDCl₃): δ = 13.8, 21.2, 22.2, 25.8, 42.2, 45.6, 126.2, 127.4, 128.45, 128.53, 129.1, 131.3, 134.6, 134.8, 137.0, 142.3, 209.1. IR: ν = 2954, 2931, 2870, 1712, 756, 702 cm^–1. ESI-HRMS: m/z calcd for C₂₁H₂₄NaO [M + Na]⁺: 315.1719; found: 315.1724. (E)-4-(4-Methylphenyl)-1,3-diphenyl-3-buten-1-one (3e) The general procedure (GP-1) was followed using 1e (26.7 mg, 0.120 mmol) and 2a (17.0 mg, 0.099 mmol) for 4 h. Purification by preparative TLC on silica gel (hexane/AcOEt = 60:1, 3×) yielded 3e (18.6 mg, 0.060 mmol, 60%) as a colorless oil. ¹H NMR (500 MHz, CDCl₃): δ = 2.34 (s, 3 H), 4.40 (s, 2 H), 7.11–7.15 (m, 3 H), 7.17–7.21 (m, 2 H), 7.23–7.28 (m, 1 H), 7.30–7.35 (m, 2 H), 7.43–7.49 (m, 4 H), 7.55–7.59 (m, 1 H), 7.94–7.98 (m, 2 H). ¹³C NMR (126 MHz, CDCl₃): δ = 21.2, 41.5, 126.2, 127.3, 128.2, 128.38, 128.43, 128.6, 129.1, 131.3, 133.2, 134.7, 134.8, 136.7, 136.9, 142.2, 197.9. IR: ν = 1682, 1327, 1211, 756, 694 cm^–1. ESI-HRMS: m/z calcd for C₂₃H₂₀NaO [M + Na]⁺: 335.1406; found: 335.1410. (E)-7-Phenyl-7,10-undecadien-5-one (3p) The general procedure (GP-1) was followed using 1a (20.2 mg, 0.100 mmol) and 2j (14.6 mg, 0.121 mmol) for 9 h. Purification by preparative TLC on silica gel (hexane/AcOEt = 30:1, 3×) yielded 3p (11.4 mg, 0.047 mmol, 47%) as a yellow oil. ¹H NMR (500 MHz, CDCl₃): δ = 0.82 (t, J = 7.5 Hz, 3 H), 1.20 (sext, J = 7.4 Hz, 2 H), 1.47 (quint, J = 7.5 Hz, 2 H), 2.35 (t, J = 7.5 Hz, 2 H), 2.88–2.95 (m, 2 H), 3.56 (s, 2 H), 5.02 (dd, J = 10.5, 1.0 Hz, 1 H), 5.09 (dd, J = 17.3, 1.2 Hz, 1 H), 5.85 (ddt, J =17.3,10.2, 6.1 Hz, 1 H), 5.96 (t, J = 7.5 Hz, 1 H), 7.18–7.32 (m, 5 H). ¹³C NMR (126 MHz, CDCl₃): δ = 13.8, 22.2, 25.8, 33.2, 41.7, 45.0, 115.5, 126.0, 127.1, 128.4, 129.2, 134.2, 135.8, 142.2, 208.4. IR: ν = 2954, 1720, 756 cm^–1. ESI-HRMS: m/z calcd for C₁₇H₂₂NaO [M + Na]⁺: 265.1563; found: 265.1559.
• 12 General Procedure for Palladium(0)-Catalyzed Ring-Opening Cross-Coupling of tert-Cyclobutenols 1 with ortho-Functionalized Iodobenzenes 2 (GP-2) A mixture of Pd₂(dba)₃ (2.3 mg, 2.5 μmol), XPhos (4.7 mg, 9.9 μmol), cyclobutenol 1 (0.120 mmol), aryl iodide 2 (0.100 mmol), and Ag₂CO₃ (30.3 mg, 0.11 mmol), in toluene (0.50 mL) was heated at 65 °C with stirring. Then, t-BuOK (2 equiv) was added to the reaction mixture, and the mixture was further heated for 2–4 h. The reaction mixture was filtered through a plug of Florisil^® washing with hexane/AcOEt (3:1), and the filtrate was concentrated. The residue was purified by preparative TLC on silica gel to afford naphthalene 4.
• 13 Selected Data for Products 2-Benzoyl-3-phenylnaphthalene (5c) The general procedure (GP-2) was followed using 1e (26.7 mg, 0.120 mmol) and 2k (23.2 mg, 0.100 mmol) for 21 h. Purification by preparative TLC on silica gel (hexane/AcOEt = 20:1, 2×) yielded 5c (15.3 mg, 0.050 mmol, 50%) as a colorless oil. ¹H NMR (500 MHz, CDCl₃): δ = 7.17–7.38 (m, 7 H), 7.42–7.47 (m, 1 H), 7.54–7.64 (m, 2 H), 7.70–7.73 (m, 2 H), 7.91–7.96 (m, 3 H), 8.04 (s, 1 H). ¹³C NMR (126 MHz, CDCl₃): δ = 126.8, 127.2, 127.8, 127.9, 128.1, 128.3, 128.4, 129.1, 129.2, 129.3, 130.0, 131.5, 132.8, 134.0, 137.4, 137.7, 138.5, 140.3, 198.3. IR: ν = 1666, 1281, 756, 694 cm^–1. ESI-HRMS: m/z calcd for C₂₃H₁₆NaO [M + Na]⁺: 331.1093; found: 331.1096. 1-Amino-2-benzoyl-3-phenylnaphthalene (5f) The general procedure (GP-2) was followed using 1e (26.7 mg, 0.120 mmol) and 2l (22.0 mg, 0.096 mmol) for 14 h. Purification by preparative TLC on silica gel (hexane/AcOEt = 30:1, 2×) yielded 5f (16.3 mg, 0.050 mmol, 52%) as a yellow oil. ¹H NMR (500 MHz, CDCl₃): δ = 5.66 (br s, 2 H), 7.02–7.14 (m, 5 H), 7.21–7.30 (m, 4 H), 7.39–7.43 (m, 2 H), 7.53–7.58 (m, 1 H), 7.59–7.64 (m, 1 H), 7.87 (d, J = 8.0 Hz, 1 H), 7.97 (d, J = 8.5 Hz, 1 H). ¹³C NMR (126 MHz, CDCl₃): δ = 116.5, 118.6, 121.6, 122.6, 125.6, 126.8, 127.6, 128.0, 128.1, 128.8, 129.1, 129.2, 131.7, 134.9, 139.9, 140.3, 141.9, 144.2, 200.4. IR: ν = 1604, 1273, 756, 694 cm^–1. ESI-HRMS: m/z calcd for C₂₃H₁₈NO [M + H]⁺: 324.1383; found: 324.1380.
• 14 Without the addition of a base, the reaction with aldehyde 2k afforded naphthalene 5 in lower yields. In contrast, no condensation was observed in the reaction with nitrile 2l in the absence of base.
• 15 Further studies have been carried out to elucidate the details of this novel oxidative imination.