A new synthetic route to 1,3,5-undecatrienes and fucoserratene

Article abstract of DOI:10.1134/S1070427208030221

A new procedure for preparing natural alkatrienes, fucoserratene and 1,3,5-undecatrienes, was developed. The key step of both syntheses is stereoselective formation of double bonds by the Wittig reaction starting from (E)-4,4-dimethoxy-2-butenal.

Full text of DOI:10.1134/S1070427208030221

ISSN 1070-4272, Russian Journal of Applied Chemistry, 2008, Vol. 81, No. 3, pp. 455 458. Pleiades Publishing, Ltd., 2008.
Original Russian Text O.A. Garibyan, A.L. Ovanesyan, G.M. Makaryan, Zh.A. Chobanyan, 2008, published in Zhurnal Prikladnoi Khimii, 2008,
Vol. 81, No. 3, pp. 470 473.
ORGANIC SYNTHESIS
AND INDUSTRIAL ORGANIC CHEMISTRY
A New Synthetic Route to 1,3,5-Undecatrienes
and Fucoserratene
O. A. Garibyan, A. L. Ovanesyan, G. M. Makaryan, and Zh. A. Chobanyan
Institute of Organic Chemistry, National Academy of Sciences of the Republic of Armenia, Yerevan, Armenia
Received May 15, 2007
Abstract A new procedure for preparing natural alkatrienes, fucoserratene and 1,3,5-undecatrienes, was
developed. The key step of both syntheses is stereoselective formation of double bonds by the Wittig reaction
starting from (E)-4,4-dimethoxy-2-butenal.
DOI: 10.1134/S1070427208030221
Conjugated trienes containing terminal vinyl group
widely occur in the nature. trans,cis- and trans,trans-
Ha
Hb
p-TSA, 20 C
C=CHCH=CHCHO
1,3,5-undecatrienes I and II were isolated from essen-
tial oils of Galbanum gum of various origins [1].
They were also found in essential oils of various algae
[2, 3] and are components of various perfume com-
pounds. In addition, triene I is one of the components
of the odor of parsley, mandarins, apples, and pears
[4]; it acts as sex pheromone on gametes of Australian
kelps [5]. (3E,5Z)-1,3,5-Octatriene III (fucoserratene)
is a pheromone isolated from fertilized ovums of
some insect species [6]. These compounds are a sub-
ject of numerous studies. They are synthesized by
heterolytic fragmentation of unsaturated 1,5-diols [6],
stereo- and regioselective palladium-catalyzed syn-
thesis [7], alkylation of terminal acetylene compounds
[8], Wittig reation [9, 10], and also using -haloalkyl-
sulfonyl bromides [11], pentadienyl dithiocarbamates
[12], and pyridazine N-oxides [13].
VI
_
+
(C H ) PC H Br,
11
6
5 3
6
Ha
NaNH , 67%
2
C=CHCH=CHCH=CH(CH2)4CH3
Hb
I
_
+
(C H ) PC H Br,
7
6
5 3
3
Ha
Hb
NaNH , 58%
2
C=CHCH=CHCH=CHCH2CH3
III
In the second route, the same reactions are per-
formed in the reverse order (Scheme 2).
Scheme 2.
RCH=CHCH=CHCH(OCH3)2
VIIa, VIIb
Here we suggest two alternative routes to the target
products, (3E,5Z)-1,3,5-undecatriene I and fucoserra-
tene III, starting from (E)-4,4-dimethoxy-2-butenal
IV. The first route is the sequence of two Wittig reac-
tions: first with triphenylmethylidenephosphorane and
then with triphenylpropylidenephosphorane or triphen-
ylhexylidenephosphorane (Scheme 1).
p-TSA, 20 C
RCH=CHCH=CHCHO
VIIIa, VIIIb
I, 34%
+
(C H ) PCH I, NaNH
2
6
5 3
3
III, 33%
Scheme 1.
(CH3O)2CHCH=CHCHO
where R = Et (VIIa, VIIIa), Am (VIIb, VIIIb).
_
+
IV
(C H ) PCH Br, BuLi
Olefination with triphenylmethylidenephosphorane
(Scheme 1) was performed at 0 C in tetrahydrofuran
(THF) in the presence of butyllithium. Since the yield
of (3E)-5,5-dimethoxy-1,1-pentadiene V did not ex-
ceed 30%, butyllithium was replaced by sodium
amide. By so doing, the yield of acetal V was in-
6
5 3
3
or
(C H ) PCH I, NaNH
3
_
+
6
5 3
3
Ha
Hb
C=CHCH=CHCH(OCH3)2
V
455

456
GARIBYAN et al.
creased to 62%. After deprotection of the carbonyl
group (20 C, acetone water, 2 : 1) in the presence of
catalytic amounts of p-toluenesulfonic acid (p-TSA),
(2E)-penta-2,4-dienal VI was prepared in 93% yield.
The second Wittig reaction with dienal VI was also
performed in THF at 0 C. The phosphonium salts
were deprotonated with sodium amide. Mixtures of
stereoisomers of 1,3,5-undecatriene I and fucoserra-
tene III were obtained in 67 and 58% yields, respec-
tively. The content of the (3E,5Z) isomers in the iso-
meric mixtures exceeded 80%.
V followed by the Wittig reaction yielded undecatri-
ene II containing 87% (E,E) isomer.
EXPERIMENTAL
1
The H NMR spectra were recorded on a Varian
VXR-300 spectrometer (300 MHz) in (CD ) CO or
3 2
CDCl . The chemical shifts ( , ppm) are given rela-
3
tive to TMS. The IR spectra were recorded on a UR-
20 spectrophotometer from thin films. GLC analysis
was performed with a Chrom-5 chromatograph (flame
ionization detector, 25 m 0.25 mm glass capillary
column, liquid phase SE-30, carrier gas nitrogen, flow
1
The isomer ratio was determined by H NMR spec-
6
troscopy from the chemical shift of the H atom.
1
6
rate 3 ml min ). Column chromatography was per-
In the (E,Z) isomer, the H signal is shifted upfield
formed on silica gel L 40/100. Thin-layer chromatog-
raphy was performed on Silufol UV-254 plates; the
chromatograms were developed by treatment with
(5.50 ppm) relative to the (E,E) isomer (5.75 ppm)
[8]. In the case of undecatriene I, the isomer ratio was
also determined by GLC on a capillary column coated
with SE-30.
iodine vapor or KMnO solution. Compound IV was
4
prepared as described in [15], and phosphonium salts,
as described in [16].
By Wittig olefination of butenal IV with triphenyl-
propylidenephosphorane and triphenylhexylidenephos-
phorane, we previously prepared mixtures of isomers
of acetals VIIa and VIIb, respectively, with more
than 95% content of (2E,4Z) isomers. The acetal pro-
tection was removed at 0 C in acetone water (2 : 1)
in the presence of catalytic amount of p-toluenesul-
fonic acid to obtain the corresponding dienals VIIIa
and VIIIb, with the configuration of (4Z) double bond
being almost fully retained [14]. Then, by the Wittig
reaction, we prepared the desired trienes: (3E,5Z)-
1,3,5-undecatriene I and fucoserratene III (Scheme 2).
(3E)-5,5-Dimethoxy-1,3-pentadiene V. a. A 1.45 N
solution of butyllithium (16.8 ml) was added dropwise
at room temperature to 8.9 g of methyltriphenylphos-
phonium bromide in 35 ml of THF. Then the mixture
was cooled to a temperature from 0 to 5 C, and a
solution of 3.0 g of butenal IV in 5 ml of THF was
added dropwise. The mixture was allowed to stand for
1 h, after which it was poured onto ice and extracted
with ether. The extract was dried over sodium sulfate.
The solvent was distilled off, and the residue was dis-
tilled in a vacuum to obtain 1.3 g (30%) of (3E)-5,5-
dimethoxy-1,3-pentadiene V, bp 72 73 C (12 mm
By choosing appropriate deprotection conditions,
from acetal VIIb we prepared (E,Z)- and (E,E)-deca-
dienals IX with the prevalence of the (E,E) isomer.
For example, at 20 C in the presence of catalytic
amounts of p-toluenesulfonic acid and equimolar
amounts of water in acetone, we prepared decadienal
IX with 81% content of the (E,E) isomer [14], which
was converted by the Wittig reaction into (3E,5E)-
1,3,5-undecatriene II with 34% yield:
1
Hg). IR spectrum, , cm : 1116 (CH O C OCH ),
3
3
1
1600 (C=C). H NMR spectrum [(CD ) CO], , ppm
(J, Hz): 3.2 s (6H, OCH ), 4.8 d (1H, H , J 5.0 ),
3 2
5
3
5,4
1b
1a
5.12 d (1H, H , J
10.5), 5.28 d (1H, H , J
1a,2
1b,2
4
16.0), 5.61 d.d (1H, H , J 15.5, J 5.0), 6.07 d.d.d
4,3
4,5
2
3
(1H, H , J
10.5, J
11.2, J
16.0, J 11.2), 6.67 d.d
2,1a
2,1b
3,4
2,3
(1H, H , J
15.5).
3,2
Found, %: C 65.56, H 9.41.
CH3(CH2)4CH=CHCH=CHCHO
C7H12O2. Calculated, %: C 65.60, H 9.44.
IX
+
(C H ) PCH I, NaNH
2
6
5 3
3
b. Methyltriphenylphosphonium iodide (28.7 g)
was added to 3.6 g of sodium amide in 40 ml of THF
under nitrogen. The mixture was refluxed for 1 h,
after which it was cooled to a temperature from 0 to
10 C, and a solution of 9.2 g of aldehyde IV in
10 ml of THF was added dropwise. The mixture was
allowed to stand dor 1 h, after which 50 ml of water
was added, and the mixture was extracted with ether.
The extract was dried over sodium sulfate, the solv-
Ha
CH3(CH2)4CH=CHCH=CHCH=C
Hb
II
Undecatriene II was also synthesized by the
Schlosser reaction. (2E,4E)-1,1-Dimethoxy-2,4-deca-
diene V was prepared in 57% yield form butenal IV
and hexyltriphenylphosphonium bromide; the product
contained 90% (E,E) isomer [14]. Deacetalization of
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A NEW SYNTHETIC ROUTE TO 1,3,5-UNDECATRIENES
457
ents were removed, and the residue was distilled in
a vacuum. Dimethoxy diene V was obtained, bp 72
73 C (12 mm Hg); yield 5.6 g (62%).
um sulfate. After removing the solvent, the crude mix-
ture was purified on a column (silica gel, hexane :
ether from 19 : 1 to 10 : 1) to obtain 0.13 g (34%)
of undecatriene I with 84% content of the (3E,5Z)
isomer.
(2E)-2,4-Pentadienal VI. p-Toluenesulfonic acid
(36 mg) was added to a mixture of 0.9 g of dimethoxy
diene V in 10 ml of acetone and 5 ml of water. The
mixture was stirred for 10 min at 20 C and neutra-
lized with Na CO , after which acetone was removed
(3E,5Z)-1,3,5-Octatriene III. a. Propyltriphenyl-
phosphonium bromide (1.4 g) was added to 0.185 g of
sodium amide in 2 ml of THF. The mixture was re-
fluxed for 1 h, after which it was cooled to a tempera-
ture from 0 to 10 C, and a solution of 0.3 g of alde-
hyde VI in 1 ml of THF was added dropwise. One
hour later, 3 ml of water was added, and the mixture
was extracted with ether. The extract was dried over
sodium sulfate. After distilling off the solvents, the
crude mixture was purified on a column (silica gel,
hexane : ether from 19 : 1 to 10 : 1) to obtain 0.23 g
(58%) of octatriene III with 85% content of the (3E,
2
3
and the residue was extracted with ether. The extract
was dried over sodium sulfate, and the crude mixture
after removing the solvent was purified on a column
(silica gel, hexane : ether = 10 : 1). (2E)-2,4-Pentadi-
enal VI was isolated; yield 534 mg (93%). IR spec-
1
1
trum, , cm : 1620 (C=C), 1675, 2720 (C=O). H
NMR spectrum [(CD ) CO], , ppm (J, Hz): 5.64 d
3 2
5a
5b
(1H, H , J
10.5), 5.81 d (1H, H , J
16.0),
5a,4
5b,4
2
6.05 d.d (1H, H , J
8.5, J 15.3), 6.40 m (1H,
2,1
2,3
1
4
3
5Z) isomer. IR spectrum, , cm : 840 [(Z)-C=C], 935
H ), 7.12 d.d (1H, H , J 15.3, J 10.3), 9.55 d
3,2
3,4
1
1
[(E)-C=C], 1560 (C=C), 3100 (CH =CH). H NMR
2
(1H, H , J
8.5) [17].
1,2
8
spectrum (CDCl ), , ppm (J, Hz): 0.9 t (3H, H , J
3
8,7
1.2,
16.0),
7
1a
(3E,5Z)-1,3,5-Undecatriene I. a. Hexyltriphenyl-
phosphonium bromide (1.6 g) was added to 0.185 g
of sodium amide in 2 ml of THF. The mixture was
refluxed for 1 h and cooled to a temperature from 0 to
10 C, and a solution of 0.3 g of dienal VI in 1 ml of
THF was added dropwise. After keeping for 1 h, 3 ml
of water was added, and the mixture was extracted
with ether and dried over sodium sulfate. After re-
moving the solvents, the crude mixture was purified
on a column (silica gel, hexane : ether from 19 : 1 to
10 : 1) to obtain 0.37 g (67%) of (3E,5Z)-1,3,5-un-
decatriene I [relative content of the (3E,5Z) isomer
7.0), 2.16 m (2H, H ), 5.10 d.d (1H, H , J
1a,1b
1b
J
10.0), 5.22 d.d (1H, H , J
1.2, J
1a,2
1b,1a
1b,2
6
5.48 d.t (1H, H , J 10.0, J 7.0), 5.96 6.56 m
6,5
6,7
2
3
4
5
(4H, H , H , H , H ). Along with these signals, we
found a signal at 5.78 d.t (1H, J 15.0, J 7.0), be-
6,5
6,7
6
longing to the H atom of (3E,5E)-1,3,5-octatriene III.
b. Methyltriphenylphosphonium iodide (6.2 g) was
added to 0.85 g of sodium amide in 6 ml of THF, and
the mixture was refluxed for 1 h. After cooling to a
temperature from 0 to 10 C, a solution of 1.7 g of
(2E,4Z)-2,4-heptadienal VIII was added dropwise.
The mixture was allowed to stand for 1 h, treated with
water, and extracted with ether. The extract was dried
over sodium sulfate. The residue after removing the
solvents was chromatographed on a column (silica
gel, hexane : ether = 20 : 1) to obtain 0.55 g (33%) of
octatriene III with 89% content of the (3E,5Z) isomer.
1
86%]. IR spectrum, , cm : 840 (C=C), 935 [(E)-
1
C=C], 1560 (C=C), 3100 (CH =CH). H NMR spec-
2
11
trum (CDCl ), , ppm (J, Hz): 0.91 t (3H, H , J
3
11,10
8
9
10
7
7.0) 1.28 1.46 m (6H, H , H , H ), 2.20 q (2H, H ,
1a
J
= J = 7.2), 5.08 d.d (1H, H , J
1.2, J
16.0), 5.50
7,6
7,8
1a,1b 1a,2
1b
10.0), 5.22 d.d (1H, H , J
1.2, J
1b,1a
1b,2
6
2
(3E,5E)-1,3,5-Undecatriene II. Methyltriphenyl-
phosphonium iodide was added to 0.13 g of sodium
amide in 2 ml of THF. The mixture was refluxed for
1 h. After cooling to a temperature from 0 to 10 C,
a solution of 0.4 g of dienal IX in 1 ml of THF was
added dropwise. One hour later, 3 ml of water was
added, and the mixture was extracted with ether. The
extract was dried over sodium sulfate. The residue
after removing the solvents was chromatographed on
a column (silica gel, hexane : ether = 20 : 1) to obtain
0.13 g (34%) of undecatriene II with 87% content of
d.t (1H, H , J 10.0, J 7.0), 5.98 6.56 m (4H, H ,
H , H , H ). Signals belonging to (3E,5E)-1,3,5-un-
decatriene II were also present: 2.14 q (2H, H , J
6,5
6,7
3
4
5
7
=
7,6
1a
J
= 7.4), 5.05 d.d (1H, H , J
1.2, J
16.0), 5.74 d.t
10.0),
7,8
1a,1b
1a,2
1b
5.19 d.d (1H, H , J
(1H, H , J
1.2, J
7.0) [9].
1b,1a
1b,2
6
15.0, J
6,5
6,7
b. Methyltriphenylphosphonium iodide (0.94 g)
was added to 0.13 g of sodium amide in 4 ml of THF,
and the mixture was refluxed for 1 h. After cooling to
a temperature from 0 to 10 C, a solution of 0.4 g of
aldehyde VIII in 1 ml of THF was added. One hour
later, 3 ml of water was added, the mixture was ex-
tracted with ether, and the extract was dried over sodi-
1
the (3E,5E) isomer. IR spectrum, , cm : 965 [(E)-
1
C=C], 1585 (C=C), 3080 (C=C). H NMR spectrum
11
[(CD ) CO], , ppm (J, Hz): 0.91 t (3H, H , J
3 2
11,10
RUSSIAN JOURNAL OF APPLIED CHEMISTRY Vol. 81 No. 3 2008

458
GARIBYAN et al.
7
8
9
10
7.0), 1.23 1.46 m (6H, H , H , H ), 2.14 q (2H, H ,
7. Teller, F., Descoins, C., and Sauvetre, R., Tetrahed-
ron, 1991, vol. 47, no. 37, p. 7767.
1a
J
7.2), 5.05 d.d (1H, H , J
1.3, J
10.0),
7,8
1a,1b
1b,2
1a,2
1b
5.19 d.d (1H, H , J
1.3, J
6.0), 5.74 d.t (1H,
8. Alami, A., Gueugnot, S., Domingues, S., and Lin-
strumelle, E., Tetrahedron, 1995, vol. 51, no. 9,
p. 1209.
1a,1b
6
2
3
H , J
14.5, J
7.2), 5.98 6.58 m (4H, H , H ,
6,5
5
6,7
4
H , H ).
9. Naf, F., Decorzant, R., Thommen, W., et al., Helv.
Chim. Acta, 1975, vol. 58, no. 4, p. 1016.
CONCLUSION
10. Goldbach, M., Takel, E., and Schneider, M.P.,
A stereoselective procedure for preparing conju-
gated alkatrienes by the Wittig reaction with (E)-4,4-
dimethoxy-2-butenal was developed.
J. Chem. Soc., Chem. Commun., 1987, no. 19, p. 1434.
11. Block, E., Aslam, M., Eswarakrishnan, V., et al.,
J. Am. Chem. Soc., 1986, vol. 108, no. 18, p. 4568.
12. Hayashi, T., Yanagida, M., Matsuda, Y., and Oishi, T.,
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