The First Facile Synthesis of Some 1,2a,3,8b-Tetrahydro-2H-Cyclobuta[c] Chromenes Through Intramolecular Alkylation of an Aromatic Ring by a Cyclobutanone

Abstract

Starting from cyclobutanones several new chromenes containing a cyclobutane ring are prepared. Ring fission of these derivatives gives easy access to functionalized 3-isoflavenes.

Key words

cyclopropanes - cyclobutanones - electrophilic aromatic substitutions - ring opening - kinetic resolution

References

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6

It has not been possible to isolate the oxaspiropentane 2e, as it is transformed to the corresponding cyclobutanone 3e during the epoxidation reaction.

8

Typical procedure for the preparation of chromenes 4a-f: A stirred solution of cyclobutanone 3 (2.7 mmol) and p-toluenesulfonic acid (0.27 mmol, 0.046 g) in benzene (10 mL) was refluxed for 6 h. The reaction mixture was diluted with CH₂Cl₂ and washed with 10% NaHCO₃ and brine, dried (Na₂SO₄) and evaporated to remove the solvent. The residue was purified by chromatography on silica gel with Et₂O-light petroleum (1:1) as eluent.
All new compounds have been fully characterized by ¹H NMR (300 MHz), ¹³C NMR (75.4 MHz) and mass spectra (70 eV). Analytical data for some representative derivatives are reported. 1f: colorless oil; yield: 70%. ¹H NMR (CDCl₃) δ: 1.00-1.22 (m. 4 H), 1.52 (d, 3 H, J = 6.6 Hz), 1.84 (s, 3 H), 5.05 (q, 1 H, J = 6.6 Hz), 6.90-7.28 (m, 5 H). ¹³C NMR (CDCl₃) δ: 1.14, 2.76, 15.10, 19.71, 78.56, 115.65, 118.76, 120.65, 124.74, 129.12, 158.16. 3e: yellow oil; yield: 85%. ¹H NMR (CDCl₃) δ: 2.48-2.58 (m, 1 H), 2.73-2.82 (m, 1 H), 2.98-3.10 (m, 1 H), 3.18-3.30 (m, 1 H), 3.97, 4.23 (AB q, 2 H, J = 9 Hz), 7.22-7.44 (m, 10 H). ¹³C NMR (CDCl₃) δ: 21.09, 44.09, 72.06, 72.54, 114.58, 121.25, 126.58, 127.50, 128.69, 129.43, 137.83, 158.43, 210.17. IR (neat, cm^-1) : 1782. MS m/z: 252 [M⁺ (0.4)], 209(5), 195(9), 159(100), 131(23), 117(60). 4e: yellow oil; yield 60%. ¹H NMR (CDCl₃) δ: 2.13-2.27 (m, 1 H), 2.19 (br s, 1 H), 2.26-2.33 (m, 2 H), 2.54-2.61 (m, 1 H), 4.05,4.14 (AB q, 2 H, J = 11.4 Hz), 6.85-7.65 (m, 9 H). ¹³C NMR (CDCl₃) δ: 19.94, 36.76, 52.91, 71.74, 72.68, 117.29, 122.08, 127.22, 127.32, 127.58, 128.57, 128.79, 129.73, 138.37, 154.17. IR (neat, cm^-1) : 3450. MS m/z: 252 [M⁺(6)], 234(5), 224(8), 121(100). 5e: red oil; yield 56%. ¹H NMR (CDCl₃) δ: 2.41 (s, 3 H), 2.81 (t, 2 H, J = 7.5 Hz), 3.99 (t, 2 H, J = 7.5 Hz), 4.78 (s, 2 H), 6.81-7.64 (m, 10 H). ¹³C NMR (CDCl₃) δ: 21.55, 26.98, 68.19, 69.39, 116.19, 121.51, 122.60, 123.25, 124.00, 127.69, 127.78, 128.02, 128.77, 128.91, 129.69, 132.69, 134.34, 13.44, 144.54, 153.89. IR (neat, cm^-1): 1160,1350.