Synthesis of (E,E)-Tricyclohexaprenol by Reactive Barium-Promoted Coupling of a Geranyl- and an Isocopalenyl Moiety

Abstract

The difficult coupling of a geranyl- and an isocopalenyl moiety to form tricyclohexaprenol could be carried out by allylation of isocopalenal with an 8-geranylbarium chloride followed by ­reduction of the so-formed hindered hydroxy group via a xanthate.

Key words

addition reactions - allylations - barium - cross-coupling - terpenoids

References

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10

Chloride 3: mp 99.5-100 °C (recrystallized from Et₂O-MeOH). ¹H NMR (300 MHz, CDCl₃): δ = 0.80, 0.82, 0.86, 0.88 (4 s, 12 H), 1.05-1.65 (m, 10 H), 1.81 (br s, 3 H), 1.85-2.05 (m, 3 H), 2.21 (m, 1 H), 3.45 (dd, J = 11.5, 6.7 Hz, 1 H), 3.75 (dd, J = 11.5, 2.4 Hz, 1 H), 5.47 (m, 1 H). ¹³C NMR (75 MHz): δ = 15.1, 15.7, 18.5, 18.7, 21.6, 21.7, 22.6, 33.1, 33.4, 37.2, 37.3, 39.8, 41.0, 41.9, 43.1, 54.8, 56.1, 58.1, 123.8, 132.2.

13

NMR data (in CDCl₃).
Ether 13: ¹H NMR (200 MHz): δ = 0.72, 0.82, 0.86, 0.87 (4 s, 12 H), 1.61 (s, 3 H), 1.68 (s, 6 H), 3.32 (s, 3 H), 3.94 (d, J = 6.7 Hz, 2 H), 5.12 (m, 1 H), 5.36 (m, 2 H). ¹³C NMR (50 MHz): δ = 14.4, 15.5, 16.1, 16.5, 18.6, 18.9, 21.8, 22.1, 22.9, 25.8, 26.4, 33.2, 33.5, 36.9, 37.3, 39.7, 39.9, 40.7, 42.0, 42.4, 55.0, 55.2, 56.3, 57.8, 69.0, 120.8, 122.0, 124.0, 135.3, 136.0,140.4.
Tricyclohexaprenol (1): ¹H NMR (500 MHz): δ = 0.72 (s, 3 H), 0.79 (dd, J = 2.0, 12.0 Hz, 2 H), 0.82, 0.86, 0.87 (3 s, 9 H), 1.61, 1.68, 1.70 (3 br s, 9 H), 1.84-1.95 (m, 4 H), 2.02-2.21 (m, 5 H), 4.15 (d, J = 7.0 Hz, 2 H), 5.11 (t, J = 7.0 Hz, 1 H), 5.36 (br s, 1 H), 5.42 (tq, J = 1.3, 7.0 Hz, 1 H). ¹³C NMR (125 MHz): δ = 14.3, 15.5, 16.1, 16.3, 18.5, 18.8, 21.7, 22.1, 22.8, 25.7, 26.2, 33.1, 33.4, 36.8, 37.2, 39.5, 39.8, 40.6, 41.9, 42.2, 54.7, 55.1, 56.3, 59.4, 122.0, 123.3, 123.9, 135.3, 136.0, 139.8.

14

Chloride 11 (138 mg, 0.32 mmol) in dry THF (1.5 mL) at -78 °C was added via a Teflon cannula to freshly prepared reactive barium [9] [12] (0.60 mmol) in dry THF (5 mL) at -78 °C under argon. The reaction was stirred for 1 h at the same temperature. Aldehyde 9 (108 mg, 0.37 mmol) in dry THF (1.5 mL) at -78 °C was then added via a Teflon cannula. After 1 h, the reaction was quenched with aq NH₄Cl, extracted with Et₂O, and worked up.

15

Ratio measured by GC. The E/Z-isomerization could have occurred either in the allylic barium reagent or during the reduction of the xanthate, which proceeds via a homoallylic radical.

16

Semi-preparative Zorbax ODS column (Du Pont). Eluent: MeOH-H₂O, 93:7, v/v. Flow rate: 30 mL/min.