Stereoselective Synthesis of Exocyclic Alkenes
FULL PAPER
sieves. The other commercial reagents were used as received. 1H (2E)-2-Allyl-1-(tert-butyldimethylsiloxy)-3,7-dimethyl-2,6-octadiene:
and 13C NMR spectra were recorded in CDCl3 on Varian Gemini-
To a solution of dry ZnBr2 (4.49 g, 19.9 mmol) in THF (25 mL) at
200 (200 MHz) and Innova-300 NMR (300 MHz) spectrometers 0 °C was added a solution of methylmagnesium bromide (3 in
using CDCl3 as an internal standard, unless otherwise noted.
Et2O, 5.3 mL, 16 mmol). The reaction mixture was stirred at 23 °C
for 30 min., and then a mixture of [Pd(PPh3)4] (277 mg, 0.24 mmol)
and (2Z)-2-allyl-1-(tert-butyldimethylsiloxy)-3-iodo-2-methyl-2,6-
octadiene (5.04 g, 12 mmol) in THF (12 mL) was added by cannula
at 0 °C. The reaction mixture was stirred for 18 h, diluted with
Et2O, washed with aqueous NH4Cl and then with aqueous
NaHCO3, dried over MgSO4, filtered, and concentrated. Filtration
on a pad of silica (pentane) gave (2E)-2-allyl-1-(tert-butyldimethyl-
siloxy)-3,7-dimethyl-2,6-octadiene (3.51 g, 95%): 1H NMR (CDCl3)
δ ϭ 0.16 (s, 6 H), 0.90 (s, 9 H), 1.70 (s, 3 H), 1.77 (s, 3 H),
2.15Ϫ2.25 (m, 2 H), 2.45Ϫ2.5 (m, 2H) 3.01 (d, J ϭ 6.0 Hz, 2 H),
4.23 (s, 2 H), 5.0Ϫ5.2 (m, 3 H), 5.85Ϫ5.9 (m, 1 H). Ϫ 13C NMR
(CDCl3): δ ϭ Ϫ5.28 (2 C), 17.55, 17.82, 18.36, 25.66, 25.96 (3 C),
26.71, 33.68, 34.71, 61.69, 114.42, 124.28, 130.19, 131.40, 132.54,
137.13.
Synthesis of (Z)-γ-Bisabolene
7-Methyl-6-octen-2-yn-1-ol (2a):[14] To a mixture of Mg turnings
(8.7 g, 360 mmol), I2 (one crystal) and HgCl2 (50 mg, 0.1 mmol) in
THF (20 mL) was added a solution of propargyl bromide (9 mL,
120 mmol) dissolved in THF (100 mL). After the addition of the
first 10 mL, the reaction mixture was heated to reflux to initiate
the reaction, and the remaining part of the solution of propargyl
bromide in THF was added at such a rate as to maintain a slight
reflux. After the addition was complete, the reaction mixture was
refluxed for 30 min., and then added to a solution of 1-bromo-3-
methyl-2-butene (6.67 g, 5.2 mL, 44 mmol) in THF (40 mL) at 23
°C. The resulting reaction mixture was refluxed for 2 h, quenched
with aqueous NH4Cl, extracted with pentane, washed with aqueous
NaHCO3, dried over MgSO4, and filtered. Evaporation of the solv-
ent followed by distillation afforded 3.5 g (74%) of 6-methyl-5-
hepten-1-yne. To a solution of this enyne (2.80 g, 25.9 mmol) in
THF (65 mL) at Ϫ78 °C were added successively a solution of
nBuLi (2.5 in hexanes, 11.4 mL, 28.5 mmol) and, after 1 h, par-
aformaldehyde (1.17 g, 38.8 mmol). The reaction mixture was then
warmed to 23 °C, quenched with aqueous NH4Cl, extracted with
Et2O, washed with aqueous NaHCO3, dried over MgSO4, filtered,
and concentrated. Chromatography on silica gel (pentane/Et2O,
70:30 v/v) afforded 4.1 g (68%) of 7-methyl-6-octen-2-yn-1-ol: 1H
NMR (CDCl3) δ ϭ 1.62 (s, 3 H), 1.70 (s, 3 H), 1.72 (s, 1 H),
2.15Ϫ2.25 (m, 4 H), 4.25 (s, 2 H), 5.15Ϫ5.2 (m, 1 H).
(2E)-2-Allyl-3,7-dimethyl-2,6-octadien-1-ol (4a): To a solution of
(2Z)-2-allyl-1-(tert-butyldimethylsiloxy)-2,3-dimethyl-2,6-octadiene
(3.51 g, 11.38 mmol) in THF (8 mL) was added tetrabutylammo-
nium fluoride (1 in THF, 14 mL, 14 mmol) at 23 °C. After 5 h,
the reaction mixture was diluted with Et2O, washed with aqueous
NH4Cl and then with aqueous NaHCO3, dried over MgSO4, fil-
tered, and concentrated to afford (2E)-2-allyl-3,7-dimethyl-2,6-
octadien-1-ol (2.0 g, 92%): 1H NMR (CDCl3) δ ϭ 1.57 (s, 3 H),
1.65 (s, 3 H), 1.74 (s, 3 H), 2.03 (br. s, 4 H), 2.89 (d, J ϭ 6.0 Hz, 2
H), 4.07 (s, 2 H), 4.95Ϫ5.1 (m, 3 H), 5.7Ϫ5.8 (m, 1 H). Ϫ 13C
NMR (CDCl3) δ ϭ 17.46, 17.78, 25.54, 26.66, 34.55, 34.61, 61.75,
114.90, 123.95, 129.82, 131.57, 134.86, 136.93.
(2Z)-2-Allyl-3-iodo-7-methyl-2,6-octadien-1-ol (3a):[15] To a solution
of 7-methyl-6-octen-2-yn-1-ol (3.45 g, 25 mmol) and copper(I) iod-
ide (0.475 g, 2.5 mmol) in dry Et2O (25 mL) was added allylmag-
nesium bromide (1 in Et2O, 75 mL, 75 mmol) dropwise at 0 °C.
After the addition was complete, the reaction mixture was stirred
at 23 °C for 20 h, and then cooled to Ϫ78 °C. A solution of I2
(19 g, 75 mmol) in THF (50 mL) was added by cannula, and the
reaction mixture was slowly warmed to 23 °C, stirred for 1 h, and
washed successively with aqueous NH4Cl, aqueous NaHCO3, and
aqueous Na2S2O3. Drying over MgSO4, filtration, concentration,
and purification by chromatography (pentane/Et2O, 90:10 v/v) pro-
vided (2Z)-2-allyl-3-iodo-7-methyl-2,6-octadien-1-ol (4.5 g, 59%,
(5Z)-5-Allyl-2,6,10-trimethyl-1,5,9-undecatriene (5a): To a solution
of n-bromosuccinimide (804 mg, 4.5 mmol) in CH2Cl2 (15 mL) was
added dimethyl sulfide (5.4 mmol, 0.40 mL) dropwise at 0 °C.[18]
To this reaction mixture was added (2E)-2-allyl-3,7-dimethyl-2,6-
octadien-1-ol (582 mg, 3 mmol) in CH2Cl2 (6 mL) dropwise at Ϫ78
°C. After stirring at 0 °C for 5 h and then at 23 °C for 18 h, the
reaction mixture was diluted with pentane, and poured into cold
water (4 mL). The organic layer was separated, washed with cold
brine, filtered quickly on a pad of silica, and concentrated to give
(2E)-2-allyl-3,7-dimethyl-2,6-octadienyl bromide, which was used
immediately without purification, as described below. To a solution
of (2E)-2-allyl-3,7-dimethyl-2,6-octadienyl bromide in THF (8 mL)
was added methallylmagnesium chloride (0.5 in THF, 12 mL,
6 mmol) at 0 °C, and the resultant mixture was stirred overnight at
23 °C. It was then diluted with pentane, poured onto ice, washed
with aqueous NH4Cl and then with aqueous NaHCO3, dried over
MgSO4, filtered, and concentrated. Chromatography on silica gel
(pentane) gave (5Z)-5-allyl-2,6,10-dimethyl-1,5,9-undecatriene (4a)
1
with a stereoselectivity Ͼ98%[16]): H NMR (CDCl3) δ ϭ 1.54 (s,
3 H), 1.60 (s, 3 H), 2.17 (apparent q, J ϭ 7.0 Hz, 2 H), 2.53 (t, J ϭ
7.0 Hz, 2 H), 3.02 (d, J ϭ 6.0 Hz, 2 H), 4.19 (s, 2 H), 5.0Ϫ5.1 (m,
3 H), 5.65Ϫ5.8 (m, 1 H). Ϫ 13C NMR (CDCl3) δ ϭ 17.79, 25.60,
27.82, 34.29, 41.57, 71.42, 107.13, 116.16, 122.07, 132.93, 134.84,
140.06.
(2Z)-2-Allyl-1-(tert-butyldimethylsiloxy)-3-iodo-7-methyl-2,6-oc-
tadiene: To a solution of (2Z)-2-allyl-3-iodo-2-methyl-2,6-octadien-
1-ol (3.43 g, 11.2 mmol) in DMF (15 mL) were added imidazole
(1.53 g, 22.4 mmol) and tert-butyldimethylsilyl chloride (2.04 g,
13.5 mmol) at 23 °C. The reaction mixture was stirred overnight,
poured into pentane, washed with aqueous NH4Cl and then with
aqueous NaHCO3, dried over MgSO4, filtered, and concentrated.
Chromatography (pentane/Et2O, 90:10 v/v) provided (2Z)-2-allyl-
1
(390 mg, 56%): H NMR (CDCl3) δ ϭ 1.62 (s, 3 H), 1.70 (s, 6 H),
1.76 (s, 3 H), 2.05Ϫ2.15 (m, 8 H), 2.80 (d, J ϭ 6.0 Hz, 2 H), 4.71
(s, 2H), 4.95Ϫ5.15 (m, 3 H), 5.7Ϫ5.8 (m, 1 H). Ϫ 13C NMR
(CDCl3) δ ϭ 17.60, 17.99, 22.54, 25.69, 27.08, 30.84, 34.47, 36.52,
36.55, 109.48, 114.66, 124.43, 130.18, 130.27, 131.35, 137.23,
146.30. Ϫ HRMS calcd. for C17H28 [M ϩ 1]: 233.2269; found
233.2270.
1-(tert-butyldimethylsiloxy)-3-iodo-7-methyl-2,6-octadiene (4.3 g, (Z)-γ-Bisabolene (1a): To a solution of (5Z)-5-allyl-2,6,10-dimethyl-
1
92%): H NMR (CDCl3) δ ϭ 0.08 (s, 6 H), 0.88 (s, 9 H), 1.63 (s, 3 1,5,9-undecatriene (116 mg, 0.5 mmol) in benzene (30 mL) was ad-
H), 1.67 (s, 3H), 2.23 (q, J ϭ 7.0 Hz, 2 H), 2.57 (t, J ϭ 7.0 Hz, 2 ded [Cl2(PCy3)2RuϭCHPh] (44 mg, 0.05 mmol, 10% mmol).[19] The
H), 3.05 (d, J ϭ 6.0 Hz, 2 H), 4.25 (s, 2 H), 5.0Ϫ5.1 (m, 3 H),
reaction mixture turned dark purple, and an evolution of gas, pre-
5.6Ϫ5.8 (m, 1 H). Ϫ 13C NMR (CDCl3): δ ϭ Ϫ5.19, 17.86, 18.25, sumably ethylene, was observed. After 1 day, the reaction mixture
25.70, 25.93, 27.87, 33.36, 41.54, 71.95, 104.32, 115.52, 122.39, was exposed to air for 5 h to destroy the catalyst. The reaction
132.78, 135.23, 140.32.
mixture was then concentrated. No aqueous workup was necessary,
Eur. J. Org. Chem. 2001, 3039Ϫ3043
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