6930 J. Agric. Food Chem., Vol. 55, No. 17, 2007
Wang and Zhang
(
9Z,12Z,15Z)-9,12,15-Octadecatrien-1-ol (2). A 250 mL dried flask
t, J ) 5.8 Hz, dC-CH
2
-Cd, C5,8), 5.29-5.41 (6H, m, CHd). 13C
was charged with fresh-prepared anhydrous diethyl ether (60 mL) under
a nitrogen atmosphere and cooled with an ice-salt bath to 0 °C, while
lithium aluminum hydride (681.2 mg, 17.96 mmol, 2.0 equiv) was
added in portions. A solution of 2.50 g (8.98 mmol) of R-linolenic
acid [(9Z,12Z,15Z)-9,12,15-octadecatrienoic acid ethanol solution,
Cayman Chemical Company, Ann Arbor, MI, ethanol was removed
by vacuum at 40 °C in a water bath] in 10 mL of anhydrous diethyl
ether was added in to the flask using a syringe, and the syringe was
washed several times with ∼7 mL of ether. The resulting mixture was
stirred for 30 min at 0 °C and then warmed to room temperature. The
reaction was monitored by GC until the peak of R-linolenic acid
disappeared (∼4 h). The reduction mixture was cooled with ice bath,
and treated by successive dropwise addition of 0.68 mL of water and
stirred for 15 min; 0.68 mL of 15% sodium hydroxide solution and
stirred for 15 min; and then 2.04 mL of water and stirred for 30 min
at room temperature. The dry granular precipitate was removed by
NMR: δ 14.11, 14.26, 20.54, 22.69, 25.52, 25.61, 27.25, 29.33, 29.35,
29.56, 29.64, 29.65, 29.66, 31.92, 127.12, 127.61, 128.23, 128.29,
130.40, 131.93. EI-MS m/z (%): 276 [M] (3), 247 (1), 233 (1), 220
+
(19), 194 (1), 177 (1), 163 (2), 149 (5), 135 (12), 121 (16), 108 (81),
95 (46), 93 (49), 79 (100), 67 (63), 55 (32).
(3Z,6Z,9Z)-3,6,9-Heneicosatriene (1c). The compound 1c (105.14
mg, 0.37 mmol) was prepared in 93% isolated yield by coupling reaction
of the triflate 3 with 2.0 equiv of propyl magnesium chloride (2.0 M
1
ether solution) in the same manner as 1a. H NMR: δ 0.88 (3H, t, J
) 6.8 Hz, CH
(18H, m, CH , C12-20), 2.03-2.10 (4H, m, CH
t, J ) 6.0 Hz, dC-CH
3
, C21), 0.98 (3H, t, J ) 7.4 Hz, CH
3 1
, C ), 1.261-1.367
2
2
-CdC, C2,11), 2.81 (4H,
1
3
2
-Cd, C5,8), 5.32-5.41 (6H, m, CHd).
C
NMR: δ 14.11, 14.27, 20.55, 22.69, 25.53, 25.62, 27.26, 29.33, 29.36,
29.57, 29.64, 29.65, 29.66, 29.68, 31.93, 127.13, 127.62, 128.24, 128.30,
130.42, 131.94. EI-MS m/z (%): 290 [M] (2), 261 (1), 234 (11), 180
(1), 163 (2), 149 (4), 135 (10), 121 (13), 108 (68), 95 (38), 93 (38), 79
(100), 67 (51), 55 (28).
+
2 4 4
filtration, the filtrate was dried over Na SO or MgSO , and the solvent
was evaporated to dryness. The crude material was purified by flash
chromatography on silica gel (60 g) using hexane-ethyl acetate (100:8
v/v) as eluent to provide 2.31 g (8.73 mmol, 97% yield) of (9Z,12Z,-
(3Z,6Z,9Z)-3,6,9-Docosatriene (1d). The compound 1d (110.21 mg,
0.36 mmol) was prepared in 93% isolated yield by coupling reaction
of the triflate 3 with 2.0 equiv of butyl magnesium chloride (2 M THF
1
1
1
0
1
5Z)-9,12,15-octadecatrien-1-ol 2 as a colorless liquid. H NMR: δ
solution) in the same manner as 1a. H NMR: δ 0.87 (3H, t, J ) 6.8
.99 (3H, t, J ) 7.6 Hz, CH
.56 (2H, quintet, J ) 7.2 Hz, CH
-Cd, C8,17), 2.80 (4H, t, J ) 6.0 Hz, dC-CH
11,14), 3.62 (2H, t, J ) 6.8 Hz, CH -O, C ), 5.30-5.41 (6H, m, CHd
3
, C18), 1.26-1.38 (10H, m, CH
, C ), 1.67 (1H, br, OH), 2.03-2.12
-Cd,
2
, C3-7),
Hz, CH , C ), 0.96 (3H, t, J ) 7.4 Hz, CH , C ), 1.25-1.34 (20 H, m,
3
22
3
1
2
2
CH , C
2
12-21
), 2.02-2.10 (4H, m, CH -Cd, C ), 2.80 (4H, t, J )
2
2,11
1
3
(4H, m, CH
2
2
6.0 Hz, dC-CH -Cd, C5,8), 5.27-5.41 (6H, m, CHd). C NMR:
2
C
)
2
1
δ 14.11, 14.26, 20.55, 22.70, 25.52, 25.61, 27.25, 29.33, 29.37, 29.57,
29.65, 29.66, 29.67, 29.68, 29.70, 31.93, 127.12, 127.61, 128.23, 128.29,
. 13C NMR: δ 14.21, 20.49, 25.47, 25.56, 25.69, 27.17, 29.18, 29.35,
+
2
9.44, 29.58, 32.71, 62.92, 127.06, 127.62, 128.20, 130.26, 131.88.
130.40, 131.93. EI-MS m/z (%): 304 [M] (4), 275 (2), 248 (15), 194
+
EI-MS m/z (%): 264 [M] (7), 235 (4), 208 (11), 149 (7), 135 (15),
(1), 163 (2), 149 (6), 135 (12), 121 (16), 108 (82), 95 (42), 93, (39),
79 (100), 67 (50), 55 (27).
1
21 (20), 108 (49), 95 (52), 93 (50), 79 (100), 67 (60), 55 (37).
9Z,12Z,15Z)-9,12,15-Octadecatrienyl Triflate (3). To a solution
of 103.2 mg (0.39 mmol) of (9Z,12Z,15Z)-9,12,15-octadecatrien-1-ol
in 5 mL of CH Cl was added 32 µL (0.39 mmol, 1.0 equiv) of
(
(3Z,6Z,9Z)-3,6,9-tricosatriene (1e). The compound 1e (117.10 mg,
0.37 mmol) was prepared in 94% isolated yield by coupling reaction
of the triflate 3 with 2.0 equiv of pentyl magnesium bromide (2 M,
2
2
2
1
pyridine at dry ice/acetone cooling (-30 °C) followed by 79 µL (0.47
mmol, 1.2 equiv) of triflic anhydride. After 30 min the reaction was
warmed to about -7 °C in an ice-salt bath and stirred for another 2.5
h, diluted with 10 mL of hexane, and filtered through a Celite pad.
The filtrate was then concentrated by a rotor evaporator to remove the
most of solvent, and the afforded crude triflate was directly used for
coupling reaction without further purification.
ether solution) in the same manner as 1a. H NMR: δ 0.86 (3H, t, J
) 6.8 Hz, CH
H, m, CH , C12-22), 2.01-2.10 (4H, m, CH
) 7.0 Hz, dC-CH
3
, C23), 0.96 (3H, t, J ) 7.4 Hz, CH
3
, C
1
), 1.24-1.35 (22
2
2
dC, C2,11), 2.80 (4H, t, J
1
3
2
-Cd, C5,8), 5.26-5.41 (6H, m, CHd).
C
NMR: δ 14.11, 14.26, 20.55, 22.70, 25.53, 25.62, 27.26, 29.34, 29.38,
29.57, 29.65, 29.66, 29.67, 29.68, 29.69, 29.70, 31.94, 127.13, 127.61,
+
128.24, 128.29, 130.41, 131.93. EI-MS m/z (%): 318 [M] (7), 289
(
3Z,6Z,9Z)-3,6,9-Nonadecatriene (1a). The freshly prepared crude
(3), 262 (20), 163 (3), 149 (7), 135 (17), 121 (20), 108 (91), 95 (54),
93 (42), 79 (100), 67 (53), 55 (29).
triflate 3 (0.39 mmol) from above reaction was dissolved in 9 mL of
dry diethyl ether and cooled with a dry ice/acetone bath at -50 °C.
Copper catalyst, Li CuCl (59 µL 0.1 M THF solution, 0.015 equiv),
2 4
RESULTS AND DISCUSSION
was added using a syringe, and the solution was stirred for 20 min.
The solution then was cooled to -78 °C, while 520 µL of methyl
magnesium bromide (3 M ether solution, 1.56 mmol, 4 equiv) was
added slowly. The reaction mixture was stirred at -78 °C for 20 min
and at -10 °C for 1 h and then treated with 1 mL of water. After the
cooling bath was removed, the mixture was diluted with 5 mL of
hexane, followed by the addition of 2 mL of 0.5 N HCl, and stirred
for another 30 min at room temperature, and then the mixture was
extracted with hexane (2 × 5 mL). The combined organic layers were
R-Linolenic acid [(9Z,12Z,15Z)-9,12,15-octadecatrienoic acid]
was selected as starting material because it was commercially
available and contained the required unsaturation and geometric
configurations. The R-linolenic acid was cleanly converted into
the corresponding alcohol, (9Z,12Z,15Z)-9,12,15-octadecatrien-
1-ol 2, in 97% isolated yield by reduction with lithium aluminum
hydride (LAH) in ether under inert atmosphere (18). An
improvement that could be made is to convert the R-linolenic
acid to the methyl ester first and then reduce it with LAH to
the alcohol. Although there is one more step reaction, the
reduction time of methyl ester to the alcohol was usually much
shorter than that of the free acid (19).
It has been noticed that cross-coupling reaction of alkyl
tosylate with Grignard reagents proceeds well (20) in THF in
the presence of a catalytic amount of copper catalyst, Li2CuCl4,
and a primary triflate showed higher activity than that of a
primary tosylate in the alkylation of triflates with alkynyllithium
reagents (21). It seemed that the (9Z,12Z,15Z)-9,12,15-octade-
catrienyl triflate might be a good candidate for sequential
coupling reaction with Grignard reagents. Treatment of the (9Z,-
2 4
washed with water and saturated brine, dried over anhydrous Na SO ,
and concentrated to afford 120 mg of crude product, which was purified
by flash chromatography on silica gel (10 g) using hexanes as an eluent
to provide 96.60 mg (0.37 mmol, 94% isolated yield) of 1a as a
1
colorless liquid. H NMR: δ 0.86 (3H, t, J ) 7.2 Hz, CH
3
, C19), 0.96
, C12-18), 2.01-
-Cd, C2,11), 2.79 (4H, t, J ) 5.9 Hz, dC-CH
(
3H, t, J ) 7.6 Hz, CH
.10 (4H, m, CH
Cd, C5,8), 5.27-5.37 (6H, m, CHd). C NMR: δ 14.10, 14.26, 20.54,
2.68, 25.52, 25.61, 27.25, 29.32, 29.34, 29.56, 29.61, 29.66, 31.91,
27.12, 127.61, 128.23, 128.29, 130.40, 131.93. EI-MS m/z (%): 262
M] (9), 233 (4), 219 (2), 206 (47), 180 (2), 163 (3), 149 (6), 135
13), 121 (16), 108 (72), 95 (41), 93 (43), 79 (100), 67 (45), 55 (21).
3
, C
1
), 1.25-1.33 (14H, m, CH
2
2
2
2
-
13
2
1
[
+
(
(3Z,6Z,9Z)-3,6,9-Eicosatriene (1b). The compound 1b (99.01 mg,
0
.36 mmol) was prepared in 92% isolated yield by coupling reaction
1
2Z,15Z)-9,12,15-octadecatrienyl triflate 3, which was easily
of the triflate 3 with 2.0 equiv of ethyl magnesium bromide (3.0 M
1
prepared from (9Z,12Z,15Z)-9,12,15-octadecatrien-1-ol 2, tri-
fluromethanesulfonic anhydride, and pyridine in dichlo-
romethane (22, 23), with methyl magnesium bromide in the
ether solution) in the same manner as 1a. H NMR: δ 0.86 (3H, t, J
6.8 Hz, CH , C20), 0.96 (3H, t, J ) 7.4 Hz, CH , C ), 1.25-1.35
16H, m, CH , C12-19), 2.01-2.10 (4H, m, CH -Cd, C2,11), 2.79 (4H,
)
(
3
3
1
2
2