Vanadium(V)-Catalyzed Oxidation of (3R)-Linalool - The Selective Formation of Furanoid Linalool Oxides and their Conversion into Isocyclocapitelline Derivatives

Abstract

Oxidation of (3R)-linalool (2) with tert-butyl hydroperoxide (TBHP) occurs at the 6,7-position to selectively afford linalool oxide cis-1, if catalyzed by vanadium(V) Schiff base complexes 4. Substituted tetrahydrofuran cis-1 and its isomer trans-1 served as starting materials for short concise syntheses of β-carbolines cis-3 and trans-3 which are lower homologues of alkaloids (-)-isocyclocapitelline and (+)-cyclocapitelline.

Key words

tert-butyl hydroperoxide - linalool oxide - oxidation - Schiff base complex - vanadium

References

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Hartung, J.; Drees, S.; Greb, M.; Schmidt, P.; Svoboda, I.; Fuess, H.; Murso, A.; Stalke, D. Eur. J. Org. Chem., submitted.

16

A solution of (3R)-linalool (2) (154 mg, 1.00 mmol) in CHCl₃ (5 mL) and vanadium(V) complex 4b (36.3 mg, 0.10 mmol) was stirred for 5 min at 25 °C. Subsequently, TBHP (273 µL, 5.5 M in nonane, 1.50 mmol) was added and the deep red reaction mixture was stirred for additional 12 h at 25 °C. Afterwards, the solvent was removed at 250 mbar/40 °C to afford a dark brown residue which was filtered through a short pad of Al₂O₃ in order to remove the catalyst. The product was washed with Et₂O (75 mL) from the column. Combined filtrate and eluate were concentrated in vacuo to provide an oil which was distilled under reduced pressure. The distillate was purified by column chromatography [SiO₂, petroleum ether-Et₂O-acetone, 5:2:1 (v/v/v); R_f cis-1 = 0.48; R_f trans-1 = 0.45] to provide 111 mg (65%) linalool oxide 1: colourless liquid, bp 80 °C/10 mbar (Kugelrohr, Lit. 78 °C/13 Torr), cis:trans = 61:39. cis-1: [α]_D ²⁵ +29.1 (c 1.1, CHCl₃), ref. [17] : [α]_D ²⁵ +11.7 (c = 0.1, CH₃OH). ¹H NMR (250 MHz, CDCl₃): δ = 1.11 (s, 3 H), 1.20 (s, 3 H), 1.29 (s, 3 H), 1.75-1.89 (m, 4 H), 2.05 (s br, 1 H, OH), 3.84 (dd, J = 8, 7 Hz, 1 H), 4.97 (dd, J = 11, 2 Hz, 1 H), 5.17 (dd, J = 17, 2 Hz, 1 H), 5.96 (dd, J = 17, 11 Hz, 1 H). trans-1: [α]_D ²⁵ -13.1 ( c 1.0, CHCl₃), ref. [17] : [α]_D ²⁵ -10.1 (c 0.1, CH₃OH). ¹H NMR (250 MHz, CDCl₃): δ = 1.10 (s, 3 H), 1.21 (s, 3 H), 1.29 (s, 3 H), 1.66-1.74 (m_c, 1 H), 1.75-1.93 (m, 3 H), 2.05 (s, br., 1 H, OH), 3.78 (t, J = 7 Hz, 1 H), 4.98 (dd, J = 11, 2 Hz, 1 H), 5.18 (dd, J = 17, 2 Hz, 1 H), 5.85 (dd, J = 17, 11 Hz, 1 H).

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Control experiments [14] indicated that vanadium(V) complex 4b catalyzes oxidation of racemic mixtures of chiral bishomoallylic alcohols without kinetic resolution.

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cis-1-[5-(1-Hydroxy-1-methylethyl)-2-methyltetrahydro-furan-2-yl]-1,2,3,4-tetrahydro-9H-β-carboline: colorless crystals, mp 119 °C; [α]_D ²⁵ -22.9 (c 0.82, CHCl₃). ¹H NMR (250 MHz, CDCl₃): δ = 1.08 (s, 3 H), 1.24 (s, 3 H), 1.38 (s, 3 H), 1.80-2.16 (m, 4 H), 2.78 (ddd, J = 12.1, 7.9, 5.5 Hz, 2 H), 3.21 (ddd, J = 12.5, 9.8, 5.5 Hz, 2 H), 4.02 (t, J = 7.0 Hz, 1 H), 4.06 (s, 1 H), 7.00-7.19 (m, 2 H), 7.24-7.36 (m, 1 H), 7.49 (m_c, J = 7.0 Hz, 1 H), 8.75 (s, 1 H), 10.23 (s, 1 H). ¹³C NMR (63 MHz, CDCl₃): δ = 20.5, 22.6, 25.0, 25.8, 27.4, 36.0, 43.9, 61.2, 71.2, 83.0, 85.6, 110.9, 112.8, 118.0, 119.0, 121.4, 135.4, 156.7, 175.5. MS (EI, 70 eV,): m/z (%) = 314 (3) [M⁺], 171 (100) [C₁₁H₁₁N₂ ⁺], 143 (6) [C₈H₁₅O₂ ⁺], 84 (11) [C₅H₈O⁺], 43 (10) [C₃H₆ ⁺]. UV/Vis (EtOH): λ_max (lg ε): 232 nm (3.76), 282 (3.81), 373 (2.46). C₁₉H₂₆N₂O₂ (314.4): Calcd C, 72.58; H, 8.33; N, 8.91. Found: C, 67.25; H, 8.26; N, 7.99. trans-1-[5-(1-Hydroxy-1-methylethyl)-2-methyltetrahydrofuran-2-yl]-1,2,3,4-tetrahydro-9H-β-carboline: colorless solid, mp 113 °C. [α]_D ²⁵ -19.5 (c 0.63, CHCl₃). ¹H NMR (250 MHz, CDCl₃): δ = 1.08 (s, 3 H), 1.22 (s, 3 H), 1.40 (s, 3 H), 1.89-2.22 (m, 4 H), 2.68-2.90 (m, 2 H), 3.22 (ddd, J = 15.0, 9.8, 5.2 Hz, 2 H), 3.99 (dd, J = 8.2, 5.4 Hz, 1 H), 4.08-4.12 (m, 1 H), 7.05-7.20 (m, 2 H), 7.33 (m_c, 1 H), 7.50 (m_c, 1 H), 8.60 (s, 1 H). ¹³C NMR (63 MHz, CDCl₃): δ = 21.6, 22.6, 24.6, 26.1, 28.8, 36.8, 43.0, 60.6, 70.4, 77.0, 86.6, 110.1, 110.9, 118.0, 119.0, 121.5, 142.3, 153.4, 174.1. MS (EI, 70 eV): m/z (%) = 314(3) [M⁺], 171(100) [C₁₁H₁₁N₂ ⁺], 143(6) [C₈H₁₅O₂ ⁺], 84(11) [C₅H₈O⁺], 43(10) [C₃H₆ ⁺]. UV/Vis (EtOH): λ_max (lg ε): 242 nm (4.52), 282 (3.85), 371 (2.57). C₁₉H₂₂N₂O₂ (314.4): Calcd C, 72.58; H, 8.33; N, 8.91. Found: C, 67.94; H, 8.06; N, 7.78.

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cis-1-[5-(1-Hydroxy-1-methylethyl)-2-methyltetrahydro-furan-2-yl]-9H-β-carboline cis-3: colorless solid, mp 161 °C. [α]_D ²⁵ -32.9 (c 0.57, CHCl₃). ¹H NMR (250 MHz, CDCl₃): δ = 1.23 (s, 3 H), 1.45 (s, 3 H), 1.78 (s, 3 H), 1.75-3.08 (m, 4 H), 4.15 (t, J = 7.3 Hz, 1 H), 7.24 (ddd, J = 7.8, 6.1, 1.8 Hz, 1 H), 7.52 (m_c, 2 H), 7.86 (d, J = 5.5 Hz, 1 H), 8.13 (d, J = 7.9 Hz, 1 H), 8.39 (d, J = 5.5 Hz, 1 H), 9.53 (s, 1 H). ¹³C NMR (63 MHz, CDCl₃): δ = 24.2, 26.2, 27.6, 27.9, 37.3, 73.3, 88.4, 90.2, 111.5, 113.4, 119.7, 121.6, 121.7, 128.3, 133.2, 136.1, 138.0, 143.2, 148.0. MS (EI, 70 eV):
m/z (%) = 310(17) [M⁺], 151(24) [C₁₆H₁₅N₂O⁺], 209 (100) [C₁₄H₁₂N₂ ⁺], 182 (11) [C₁₀H₁₆NO₂ ⁺], 43 (9) [C₂H₄O⁺]. UV/Vis (EtOH): λ_max (lg ε): 242 nm (4.52), 288 (4.26), 348 (3.77). C₁₉H₂₂N₂O₂ (310.4): Calcd C, 73.52; H, 7.14; N, 9.03. Found: C, 72.86; H, 7.11; N, 8.68. trans-1-[5-(1-Hydroxy-1-methylethyl)-2-methyltetrahydrofuran-2-yl]-9H-β-carboline trans-3: colorless solid, mp 158 °C. [α]_D ²⁵
-50.5 (c 0.5, CHCl₃). ¹H NMR (250 MHz, CDCl₃): δ = 1.25 (s, 3 H), 1.38 (s, 3 H), 1.72 (s, 3 H), 1.75-2.10 (m, 4 H), 4.15 (t, J = 7.6 Hz, 1 H), 7.22 (ddd, J = 7.9, 6.4, 1.5 Hz, 1 H), 7.48 (m_c, 2 H), 7.86 (d, J = 5.2 Hz, 1 H), 8.11 (d, J = 7.5 Hz, 1 H), 8.36 (d, J = 5.2 Hz, 1 H), 10.48 (s, 1 H). ¹³C NMR (63 MHz, CDCl₃): δ = 26.2, 26.7, 26.8, 28.4, 38.6, 72.6, 86.0, 88.2, 111.9, 114.1, 119.7, 121.5, 121.9, 128.4, 132.6, 133.0, 137.7, 142.9, 148.9. MS (EI, 70 eV): m/z (%) = 310 (17) [M⁺], 151 (24) [C₁₆H₁₅N₂O⁺], 209 (100) [C₁₄H₁₂N₂ ⁺], 182 (11) [C₁₀H₁₆NO₂ ⁺], 43(9) [C₂H₄O⁺]. UV/Vis (EtOH): λ_max (lg ε): 227 nm (4.09), 289 (4.03), 340 (3.57). C₁₉H₂₂N₂O₂ (310.4): Calcd C, 73.52; H, 7.14; N, 9.03. Found: C, 72.86; H, 7.11; N, 8.68.