S. Suntornchashwej et al. / Tetrahedron 63 (2007) 3217–3226
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dry two-neck flask at ꢀ78 ꢁC condensing approximately
80 ml of liq. NH3. Acetone–dry ice bath was, then, replaced
with acetonitrile–dry ice (temp ꢀ35 to ꢀ40 ꢁC). A solution
of 15 (2.0 g, 6.4 mmol) in 3 ml of tBuOH and 10 ml of THF
was added via syringe. Small piece of Li wire was added to
the stirred solution until deep blue solution persists for more
than 1 h. Solid NH4Cl of 1 g was then added to neutralize
tBuOLi; ammonia was allowed to evaporate overnight. The
mixture was diluted with ice-water and extracted with
Et2O. Combined organic extracts were washed with aq
NH4Cl, brine, dried (Na2SO4), and concentrated. The pale
yellow oily residue, 1.8 g, was subjected to SiO2 column
(0–10% EtOAc–Hex) yielding 1.64 g of 16a (81% yield).
(CH2-2), 36.4 (CH2-6), 56.5 (7-OCH3), 83.8 (CH-7), 127.9
(CH-5), 130.1 (CH-4), 177.5 (C-1); IR (KBr): n 2927,
2856, 1713, 1457, 1183, 970 cmꢀ1; HRMS (EI) C15H28O3
[M]+ calcd: 256.2038, found: 256.2032.
4.1.7. (S,E)-1-(Tetrahydro-2H-pyran-2-yloxy)tetradec-4-
en-7-ol, 18. Using the same procedure as described for 14a,
compound 14b (2.16 g, 77% in three steps) was obtained
from 6b. To a solution of 14b, 2.16 g (7.0 mmol), in 60 ml
THF was added 1.5 g (27.8 mmol) of NaOMe powder. The
resulting slurry was heated at 40 ꢁC for 1 h and LiAlH4 pow-
der, 580 mg (14.0 mmol), in 20 ml dry THF was then added
at this temperature in several portion via syringe. The flask
was heated to reflux at 80 ꢁC under N2 atmosphere for
24 h. The excess LiAlH4 was quenched by slowly dropping
80 ml of wet Et2O at room temperature. The mixture was
poured into 40 ml cold Na–K tartrate and stirred for 1 h.
The precipitate was filtered through a pad of Celite and
washed with Et2O. The filtrate was partitioned with cold
Et2O. The combined organic extracts were washed with
brine, dried (Na2SO4), and concentrated. The residual oil,
2.5 g, was subjected to SiO2 column (20% EtOAc–Hex)
yielding 1.66 g of 18 (76% yield).
Compound 16a: pale yellow oil; Rf 0.34, EtOAc–hexane
(1:4); [a]2D8 +10.4 (c 2.28, CHCl3); 1H NMR (CDCl3,
400 MHz) dH 0.88 (3H, dist. t, 7.2), 1.20–1.34 (10H, br s),
1.40–1.95 (10H, m), 2.05–2.40 (4H, m), 3.16 (1H, m),
3.35 (3H, s), 3.40–4.00 (4H, m), 4.60 (1H, t, 4.4), 5.38–
5.54 (2H, dd, 15.2, 6.4); IR (KBr): n 2923, 2858, 1456,
1353, 1101, 1036 cmꢀ1; elemental analysis calcd for
C20H38O3: C 73.57, H 11.73; found: C 73.57, H 11.94.
4.1.5. (R,E)-7-Methoxytetradec-4-en-1-ol, 17a. p-Toluene
sulfonic acid (PTS) monohydrate, 4.3 g, was added in
several portions to a solution of 16a, 1.5 g (4.59 mmol), in
25 ml of MeOH (pH 3). The reaction mixture was stirred
at 40 ꢁC for 3 h. The reaction was neutralized with 90 ml
of satd NaHCO3. The aqueous phase was partitioned with
cold Et2O (ꢂ2). The combined organic extracts were washed
with brine and dried (Na2SO4). After removal of solvent by
rotary evaporation and purification by SiO2 column (10–
20% EtOAc–hexane), 17a was obtained (1.31 g, quant.
yield).
Compound 14b: colorless oil; Rf 0.23, EtOAc–Hex (1:4);
1
[a]2D7 ꢀ2.25 (c 0.5, CHCl3); H NMR (CDCl3, 400 MHz)
and 13C NMR (CDCl3, 100 MHz) spectra were identical to
14a; MS (EI) C19H33O3 [MꢀH]ꢀ calcd: 309.24, found:
309.24.
Compound 18: pale yellow oil; Rf 0.23, EtOAc–Hex (1:4);
1
[a]2D8 +1.75 (c 0.5, CHCl3); H NMR (CDCl3, 400 MHz)
dH 0.79 (3H, dist. t, 6.4), 1.30–1.90 (20H, br s), 1.95–2.30
(4H, m), 3.30.3.90 (5H, m), 4.55 (1H, m), 5.35–5.60 (2H,
m); IR (KBr): n 3452, 2943, 2857, 1456, 1353, 1120,
1035, 812 cmꢀ1; HRMS (EI) C19H36O3 [M]+ calcd:
312.2664, found: 312.2694.
Compound 17a: pale yellow oil; Rf 0.17, EtOAc–hexane
(1:4); [a]2D8 +11.3 (c 1.28, CHCl3); 1H NMR (CDCl3,
400 MHz) dH 0.89 (3H, dist. t, 7.2), 1.20–1.40 (10H, br s),
1.45 (2H, m), 1.65 (2H, m), 2.12 (2H, q, 6.8), 2.20 (2H, t,
5.6), 3.17 (1H, pent, 6.0), 3.33 (3H, s), 3.66 (2H, t, 8.8),
5.35–5.541 (2H, dd, 15.2, 6.4); IR (KBr): n 3364, 2928,
2858, 1457, 1366, 1097, 969 cmꢀ1; elemental analysis calcd
for C15H30O2: C 74.32, H 12.47; found: C 74.33, H 12.43.
4.1.8. 2-((S,E)-7-Methoxytetradec-4-enyloxy)-tetra-
hydro-2H-pyran, 16b. A suspension of 50–70% sodium
hydride suspension in oil, 1.0 g (18.3 mmol), in 10 ml
DMSO was transferred to a solution of 18 (1.60 g,
6.1 mmol) in 40 ml dry THF at room temperature. Methyl
iodide, 1.25 ml (18.3 mmol), was introduced into the result-
ing white suspension. The mixture was heated to reflux for
overnight. Pre-cooled Et2O, 10 ml, was cautiously added
in flask and the mixture was poured into crushed ice. The
aqueous layer was extracted with cold Et2O (ꢂ2). The com-
bined organic extracts were washed with satd NH4Cl, brine,
dried (Na2SO4), and concentrated. The residual oil was sub-
jected to SiO2 column (10% EtOAc–Hex) yielding 1.62 g of
16b (82% yield).
4.1.6. (R,E)-7-Methoxytetradec-4-enoic acid, 2a. To a so-
lution of 17a, 850 mg (3.50 mmol), in 50 ml acetone was
added Jone’s reagent at 0 ꢁC until reaction color remain.
Excess Jone’s reagent was destroyed by slowly adding iso-
propanol. Top layer was decanted, and the lower layer was
extracted with cold Et2O. Combined organic extracts were
washed with brine, dried (Na2SO4), and concentrated. The
crude product was purified by SiO2 column using 1% acetic
acid in EtOAc as eluting solvent giving 830 mg of 2a (93%
yield).
Compound 16b: pale yellow oil; Rf 0.34, EtOAc–hexane
(1:4); [a]2D8 ꢀ10.34 (c 0.5, CHCl3); 1H NMR (CDCl3,
400 MHz) and 13C NMR (CDCl3, 100 MHz) spectra were
identical to 16a; HRMS (EI) C20H38O3 [M]+ calcd:
326.2821, found: 326.2802.
Compound 2a: pale yellow oil; Rf 0.43, EtOAc–hexane
(1:1); [a]2D8 +11.2 (c 1.30, CHCl3); 1H NMR (CDCl3,
400 MHz) dH 0.89 (3H, dist. t, 7.2), 1.20–1.40 (10H, br s),
1.45 (2H, m), 2.21 (2H, t, 6.0), 2.36 (2H, m), 2.39 (2H,
m), 3.17 (1H, pent, 6.0), 3.33 (3H, s), 5.35–5.541 (2H, dd,
15.2, 6.4); 13C NMR (CDCl3, 100 MHz) dC 14.1 (CH3-14),
22.6 (CH2-13), 25.3 (CH2-9), 27.7 (CH2-3), 29.3 (CH2-
10), 29.7 (CH2-11), 31.8 (CH2-12), 33.4 (CH2-8), 33.7
4.1.9. (R,E)-7-Methoxytetradec-4-en-1-ol, 17b. Using the
same procedure as described for 17a, compound 17b
(1.0 g, 89% yield) was obtained from 16b (1.5 g,
4.60 mmol).