Stereoselective Total Synthesis of the Sesquiterpene (±)-β-Isocomene

Abstract

Application of the Lewis acid mediated [3+2] cycloaddition of allyl-tert-butyldiphenylsilane combined with a modified Fleming-Tamao oxidation provides a stereoselective route to the triquinane sesquiterpene (±)-β-isocomene.

Key words

cycloadditions - Lewis acids - silicon - stereoselective synthesis - terpenoids

References and Notes

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17

Characteristic Spectroscopic Data of 10, 11, (±)-1, and (±)-2:
Compound 10: colorless crystals, mp 112 °C. ¹³C NMR and DEPT (125 MHz, CDCl₃): δ = 18.60 (C), 19.83 (CH₃), 21.64 (CH), 23.23 (CH₂), 23.72 (CH₃), 28.47 (3 CH₃), 35.46 (CH₂), 40.17 (CH₂), 43.21 (CH₂), 44.92 (CH₂), 45.83 (C), 53.14 (CH₂), 59.61 (C), 62.43 (C), 127.48 (4 CH), 129.11 (2 CH), 133.76 (C), 134.12 (C), 136.47 (2 CH), 136.53 (2 CH), 223.74 (C=O). Anal. Calcd (%) for C₂₉H₃₈OSi: C, 80.87; H, 8.89. Found: C, 80.64; H, 8.26.
Compound 11: colorless oil. ¹³C NMR and DEPT (125 MHz, CDCl₃): δ = 21.12 (CH₃), 22.96 (CH₂), 23.00 (CH₃), 35.58 (CH₂), 41.29 (CH₂), 45.48 (CH₂), 46.23 (C), 49.07 (CH₂), 50.19 (CH₂), 57.46 (C), 61.44 (C), 71.76 (CH), 223.43 (C=O).
(±)-β-Isocomene [(±)-1]: colorless crystals, mp 76-82 °C. IR (ATR): ν = 3073, 2925, 2869, 2854, 1655, 1460, 1376, 1260, 1106, 1024, 878 cm^-1. ¹H NMR (500 MHz, CD₂Cl₂): δ = 0.92 (d, J = 7.0 Hz, 3 H), 0.99 (s, 3 H), 1.10 (s, 3 H), 1.22-1.68 (m, 10 H), 2.00 (m, 1 H), 2.10 (d, J = 14.4 Hz, 1 H), 2.34 (dt, J = 14.4, 2.4 Hz, 1 H), 4.60 (m, 1 H), 4.63 (m, 1 H). ¹³C NMR and DEPT (125 MHz, CD₂Cl₂): δ = 18.08 (CH₃), 23.53 (CH₃), 24.27 (CH₃), 24.33 (CH₂), 30.55 (CH₂), 34.87 (CH₂), 40.83 (CH), 41.95 (CH₂), 43.15 (CH₂), 48.23 (CH₂), 49.68 (C), 55.14 (C), 67.01 (C), 100.79 (CH₂), 162.76 (C). MS (EI): m/z (%) = 204 (21) [M⁺], 189 (68), 175 (12), 162 (15), 161 (35), 149 (22), 148 (29), 147 (49), 134 (28), 133 (42), 122 (29), 121 (44), 120 (31), 119 (40), 109 (68), 108 (100), 107 (60). Anal. Calcd (%): for C₁₅H₂₄O: C, 88.16; H, 11.84. Found: C, 88.27; H, 11.98.
(±)-Isocomene [(±)-2]: colorless oil. IR (ATR): ν = 3020, 2927, 2866, 2853, 1672, 1458, 1443, 1375, 1002, 940, 845 cm^-1. ¹H NMR (500 MHz, CDCl₃): δ = 0.85 (d, J = 7.2 Hz, 3 H), 1.026 (s, 3 H), 1.030 (s, 3 H), 1.14-1.43 (m, 5 H), 1.48-1.58 (m, 4 H), 1.55 (d, J = 1.3 Hz, 3 H), 1.70-1.73 (m, 1 H), 1.99 (m, 1 H), 4.85 (m, 1 H). ¹³C NMR and DEPT (125 MHz, CDCl₃): δ = 13.00 (CH₃), 17.27 (CH₃), 23.16 (CH₃), 23.71 (CH₃), 24.01 (CH₂), 31.91 (CH₂), 33.62 (CH₂), 37.22 (CH₂), 39.88 (CH), 42.60 (CH₂), 56.61 (C), 59.86 (C), 63.75 (C), 132.66 (CH), 142.81 (C). MS (EI): m/z (%) = 204 (10) [M⁺], 189 (16), 175 (7), 162 (100), 161 (17), 147 (49), 134 (18), 133 (19), 119 (31), 105 (20), 91 (18). Anal. Calcd (%) for C₁₅H₂₄O: C, 88.16; H, 11.84. Found: C, 88.20; H, 11.80.

18

Crystal data for 10: C₂₉H₃₈OSi, crystal size: 0.60 × 0.40 × 0.40 mm³, M _r = 430.68 g mol^-1, monoclinic, space group P2₁/c, λ = 0.71073 Å, a = 13.4071(14), b = 12.1653(9), c = 16.2492(17) Å, β = 109.414(11)°, V = 2499.6(4) ų, Z = 4, ρ _calcd = 1.144 g cm^-3, µ = 0.112 mm^-1, T = 200(2) K, θ range = 2.14°-25.85°; reflections collected: 18979, independent: 4787 (R _int = 0.0393). The structure was solved by direct methods and refined by full-matrix least-squares on F ²; R ₁ = 0.0481, wR ₂ = 0.1275 [I > 2σ(I)]; maximal residual electron density: 0.424 e Å^-3. CCDC 646230 contains the supplementary crystallographic data for this structure. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.

22

Ratio of compound 15/monoalkylated isomer 1/monoalkylated isomer 2/dialkylated product 1/dialkylated product 2 = 78.2:14.0:3.6:2.2:2.0.