In conclusion, we have developed a novel protocol for the
efficient synthesis of megatomic acid in overall 45% yield with
97% stereoselectivity (as determined by GC analysis) and this
new method appears to be an alternative to previously report-
ed methods.
6.82 Hz). HR-MS m/z [M]`: calc. for C
found: 208.1815.
H
O: 208.1827,
14 24
(3E,5Z)-Tetradecadien-1-ol (6). To a solution of 5 (1.0 g, 4.8
mmol) in THF (40 ml) at [10 ¡C was added over a period of
30 min a solution of disiamylborane (23.4 mmol) [prepared
from 2-methyl-2-butene (2.98 ml, 28.2 mmol), THF (100 ml),
Experimental
BH É THF (1.0 M in THF, 23.4 ml, 23.4 mmol), 0 ¡C, 30 min].
3
The reaction mixture was stirred for 20 min at [10 ¡C, then
General procedures
warmed up to 0 ¡C and left for 4 h. Acetic acid (6.2 ml) was
added and the reaction was heated at 60 ¡C for 6 h, then
cooled to room temperature and stirred for an additional 12
h. The reaction was quenched by the addition of NaOH (6 M,
20 ml) at [5 ¡C, followed by dropwise addition of hydrogen
peroxide (30% aq, 5 ml) and warmed to 40 ¡C for 30 min. The
reaction was cooled to room temperature and diluted with
diethyl ether (30 ml) and water (30 ml). The layers were
separated and the aqueous layer was extracted with diethyl
ether; the combined organic layers were washed with saturat-
ed brine (2 ] 30 ml) and dried over anhydrous Na SO . The
IR spectra were measured as Ðlms with a Nicolet FT/IR-740
spectrometer and 1H-NMR spectra were recorded with TMS
as an internal standard in CDCl with a Varian Gemini 200
3
MHz instrument. High-resolution mass spectra (70 eV) were
measured with a VG Micromass 7070 H apparatus. Gas chro-
matography was performed with a Shimadzu GC-17A instru-
ment, using a Neutrabond-1 capillary column (0.25 mm ] 15
m; GL Sciences) operated with a temperature program of 2
min at 80 ¡C, then ramping from 80 to 220 ¡C at 6 ¡C min~1;
splint vent closed for 1 min, injection at 250 ¡C; N gas at 1.0
2
kg cm~2 at inlet and recorded as t . The olfactory sensitivity
R
2
4
solvent was removed in vacuo at reduced pressure; the
residual product was puriÐed by column chromatography on
silica gel using hexaneÈethyl acetate (90 : 10) as the eluent, to
was recorded on an EAG, Syntech (Hillversum, The
Netherlands).
1-Decyne and 3-butyn-1-ol were commercially available
and used without further puriÐcation. Diethyl ether and THF
were dried and distilled according to literature procedures.19
a†ord 850 mg of 6 (85%). IR (Ðlm) l /cm~1: 3345 (OH),
max
2980 (CÈH), 2960 (CÈH), 1640 (C2C), trans def. 980 (CÈH), cis
def. 723 (CÈH). 1H NMR (CDCl ) d: 0.90 (3H, distorted t,
3
J \ 7.0), 1.10È1.55 (13H, mult), 2.15 (2H, quart, J \ 6.9), 2.35
Syntheses
(2H, quart, J \ 6.9), 3.70 (2H, t, J \ 6.8), 5.35 (1H, dt,
J \ 10.9, 7.6), 5.60 (1H, dt, J \ 15.0, 7.5), 5.90 (1H, dd,
J \ 11.0, 10.9), 6.35 (1H, ddd, J \ 15.3, 11.0, 1.3 Hz). HR-MS
3,5-Tetradecadiyn-1-ol (4). A solution of hydroxylamine
hydrochloride (1.25 g, 18 mmol) in water (5 ml), 70% aqueous
ethylamine (10 ml), and copper(I) chloride (187 mg, 1.7 mmol)
in methanol (12 ml) were placed in a round-bottom Ñask. Air
was completely replaced by nitrogen and, while stirring, 1-
decyne (2, 3.5 g, 25 mmol) was added in one portion. To the
resulting yellow suspension, 4-bromo-3-butyn-1-ol (3, 3.75 g,
25 mmol) was added over a period of 30 min while main-
taining the temperature between 30È35 ¡C. After an additional
15 min at 40 ¡C, a solution of KCN (0.65 g, 10 mmol) and
m/z [M]`: calc. for C
H
O: 210.1984, found: 210.1973.
14 26
(3E,5Z)-Tetradecadienoic acid (1). To a stirred solution of
chromium trioxide (190 mg, 1.90 mmol) in 1.5 M H SO (1.25
2
4
ml), maintained between 5 and 10 ¡C, was added a solution of
6 (400 mg, 1.90 mmol) in acetone (23 ml) over a period of 30
min. The mixture was stirred for another 2 h at room tem-
perature; isopropanol (2 ml) and diethyl ether (100 ml) were
then added. The organic layer was decanted, washed with
brine (3 ] 50 ml) and solvent removed in vacuo. The residue
was diluted with diethyl ether and treated with 1 M NaOH
(2 ] 10 ml). The layers were separated and the aqueous layer
acidiÐed with 6 M H SO and back-extracted with diethyl
NH Cl (2.5 g, 46.7 mmol) in water (40 ml) was added and the
4
mixture stirred for 20 min. The product was isolated by
extraction with diethyl ether (3 ] 100 mL). The combined
organic extracts were washed with aqueous NH Cl solution,
4
dried over Na SO and evaporated to a†ord the crude com-
2
4
ether (3 ] 10 ml). The organic layer was washed with water,
2
4
pound, which was puriÐed by column chromatography on
brine, dried over anhydrous Na SO and the solvent was
silica gel, using hexaneÈethyl acetate (90 : 10) as the eluent to
2
4
removed in vacuo. Final puriÐcation was accomplished by
column chromatography on silica gel, using hexaneÈethyl
acetate (2 : 1) as the eluent to a†ord 350 mg of megatomic acid
(1) as an oily liquid (83%). The retention time by GC analysis
matched that of an authentic sample.5 IR (Ðlm) l /cm~1:
3450 (COOH), 2980 (CÈH), 2960 (CÈH), 1640 (C2C), trans def.
a†ord 4.6 g of compound 4 (92%). IR (Ðlm) l /cm~1: 3345
max
(OH), 2930 (CÈH), 2160 (C3 C). 1H NMR (CDCl ) d: 0.90 (3H,
3
distorted t, J \ 7.0), 1.20È1.60 (12H, mult), 1.80È1.90 (1H,
OH), 2.10 (2H, t, J \ 6.0), 2.50 (2H, t, J \ 6.0), 3.30 (2H, t,
J \ 6.0 Hz). HR-MS: m/z [M]`: calc. for
206.1670, found: 206.1663.
C
H
O:
max
14 22
980 (CÈH), cis def. 723 (CÈH). 1H NMR (CDCl ) d: 0.90 (3H,
3
distorted t, J \ 7.0), 1.25 (12H, mult), 2.05 (2H, distorted
(E)-Tetradeca-3-en-5-yn-1-ol (5). To a suspension of lithium
aluminum hydride (210 mg, 5.5 mmol) in diethyl ether (15 ml)
at [5 ¡C under nitrogen, was added a solution of 4 (2.30 g,
11.15 mmol) in diethyl ether (10 ml) dropwise over a period of
15 min. The reaction mixture was stirred for 2 h at 35 ¡C and
then cooled to 0 ¡C. The reaction mixture was diluted with
diethyl ether (20 ml) and quenched with 2 N HCl. The layers
were separated and the aqueous layer was extracted with
ether; the combined organic layers were washed with saturat-
ed brine and dried over anhydrous Na SO . The solvent was
quart, J \ 6.9), 3.00 (2H, d, J \ 6.9), 5.35 (1H, dt, J \ 10.9,
7.6), 5.60 (1H, dt, J \ 15.0, 7.5), 5.90 (1H, dd, J \ 11.0, 10.9),
6.35 (1H, ddd, J \ 15.3, 11.0, 1.3 Hz). HR-MS m/z [M]`:
calc. for C
H
O : 224.1776, found; 224.1768.
14 24
2
EAG recording
The olfactory sensitivity of a male black carpet beetle to (3E,
5Z)-tetradecadienoic acid was recorded by the electro-
antennegram recording technique. 10 ll of a 0.1% solution of
the synthetic compound in hexane were placed on a Ðlter
paper (8 ] 60 mm); after complete evaporation of the solvent
the Ðlter paper was carefully inserted into a Pasteur pipette
and air pu†ed onto a beetle antenna Ðxed between two silver
electrodes. At the same time, air from a pipette with a Ðlter
paper of the same size treated with 10 ll of hexane was pu†ed
2
4
removed in vacuo. The product was puriÐed by column chro-
matography using hexaneÈethyl acetate (90 : 10) as the eluent
to a†ord 1.6 g of 5 (70%). IR (Ðlm) l /cm~1: 3345 (OH),
max
2930 (CÈH), 2160 (C3 C), 1660 (C2C), trans def. 975 (CÈH). 1H
NMR (CDCl ) d: 0.95 (3H, distorted t, J \ 7.0), 1.20È1.60
3
(13H, mult), 2.25 (2H, quart, J \ 6.8), 2.50 (2H, t, J \ 6.8), 3.65
(2H, t, J \ 6.8, 5.55 (1H, d, J \ 15.9), 6.00 (1H, dt, J \ 15.9,
224
New J. Chem., 2001, 25, 223È225
Yadav
