Improved synthesis of (9Z)-9,13-tetradecadien-11-ynal, the sex pheromone of the avocado seed moth, Stenoma catenifer

Article abstract of DOI:10.1016/j.tetlet.2010.01.010

The terminal dienyne of (9Z)-9,13-tetradecadien-11-ynal, the sex pheromone of the avocado seed moth, Stenoma catenifer, was constructed by coupling a vinyl iodide precursor with commercially available 1-buten-3-yne with Pd catalysis, resulting in a short and efficient synthesis of the pheromone.

Full text of DOI:10.1016/j.tetlet.2010.01.010

Tetrahedron Letters 51 (2010) 1336–1337
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Tetrahedron Letters
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Improved synthesis of (9Z)-9,13-tetradecadien-11-ynal, the sex pheromone
of the avocado seed moth, Stenoma catenifer
*
Yunfan Zou, Jocelyn G. Millar
Department of Entomology, University of California, Riverside, CA 92521, USA
a r t i c l e i n f o
a b s t r a c t
Article history:
The terminal dienyne of (9Z)-9,13-tetradecadien-11-ynal, the sex pheromone of the avocado seed moth,
Stenoma catenifer, was constructed by coupling a vinyl iodide precursor with commercially available 1-
buten-3-yne with Pd catalysis, resulting in a short and efficient synthesis of the pheromone.
Ó 2010 Elsevier Ltd. All rights reserved.
Received 26 November 2009
Revised 5 January 2010
Accepted 6 January 2010
Available online 11 January 2010
Keywords:
(9Z)-9,13-Tetradecadien-11-ynal
1-Buten-3-yne
Sonogashira coupling
Conjugated dienyne
The avocado seed moth, Stenoma catenifer, is a major pest of
commercial avocado production in South and Central America,
with damage in some areas being so severe that the insect limits
or even prevents commercial cultivation of avocadoes.1 However,
the seed moth has not yet become established in avocado produc-
tion areas of the United States, although United States Department
of Agriculture risk assessments have identified S. catenifer as one of
the most serious threats to the US avocado industry.2
As part of an ongoing project to provide growers, exporters, and
regulatory agencies with a method for detection of S. catenifer, we
recently identified (9Z)-9,13-tetradecadien-11-ynal 1 as the sex
attractant pheromone of the seed moth.3 Field trials have now ver-
ified the biological activity of the pheromone, and protocols for its
use have been worked out.4 However, commercialization of the
pheromone has been slowed by the relatively inefficient synthesis
used for its production, particularly the multistep construction of
the terminal dienyne unit. Because we did not initially know the
relative positions or stereochemistry of the alkene and alkyne
bonds in the pheromone, our original synthesis3 was designed to
be flexible so that each of the two alkenes and the alkyne in the
conjugated system could be installed in any one of the three
possible positions. This requirement for flexibility resulted in the
synthesis being longer than might be required for a single specific
target. Improvements in the efficiency of several steps increased
the overall yield, but still required a three-step sequence to assem-
ble the terminal dienyne (Sonogashira coupling of an alkenyl
iodide with propargyl alcohol, oxidation of the resulting propargyl
alcohol to the aldehyde, and installation of the terminal double
bond with a Wittig reaction).3 It occurred to us that it might be
possible to install the terminal enyne in a single step via a
Sonogashira coupling between the vinyl iodide 4 and commercially
available 1-buten-3-yne (vinyl acetylene). A survey of the litera-
ture revealed only a single report of this type of coupling.
Specifically, De Meijere and co-workers showed that various 1,5-
dien-3-ynes could be prepared by Sonogashira coupling of an alke-
nyl halide with a substituted enyne.5 However, when 1-buten-3-
yne was used, the yield was low and styrene was identified as
the major product from a palladium-catalyzed formal [4+2] cyclo-
addition between two vinyl acetylene molecules.5 In addition to
this undesired side reaction, a further concern that became appar-
ent for our particular application was that 4 and 5 have almost the
same TLC Rf value and GC retention time. Therefore, if the reaction
did not go to completion, separation of the product from unreacted
starting material would be difficult, particularly on the larger
scales required for commercially useful s\yntheses. After some
experimentation with various ratios of the vinyl iodide 4 and vinyl
acetylene, we found that the desired Sonogashira coupling pro-
ceeded cleanly to give the desired dienyne product, with complete
consumption of the starting material, using 2.5 or more equiva-
lents6 of commercial 1-buten-3-yne (41.1 wt % in xylene; GFS
Chemicals), producing dienynal 1 in five steps from the readily
available starting material 2 (Fig. 1).
Thus, deprotonation of a THF solution of THP-protected 9-de-
cyn-1-ol 27 with BuLi at À78 °C, followed by the addition of a solu-
tion of iodine in THF gave iodoalkyne 3.4,8 Stereospecific reduction
with dicyclohexylborane in THF followed by protonolysis gave
Z-iodoalkene 4.4,9 Sonogashira coupling of the iodoalkene with
* Corresponding author. Tel.: +1 951 827 5821; fax: +1 951 827 3086.
E-mail address: Jocelyn.millar@ucr.edu (J.G. Millar).
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.01.010

Y. Zou, J. G. Millar / Tetrahedron Letters 51 (2010) 1336–1337
1337
I
1) BuLi
OTHP
OTHP
2) I2
2
3, 95%
1) BH3-DMS, cyclohexene
2) HOAc
OTHP
Pd(PPh3)2Cl2, CuI, pyrrolidine
I
4, 50%
OTHP
OH
PTSA, MeOH
5, 81%
6, 90%
O
H
PCC, 4Å MS
CH2Cl2
1, 71%
Figure 1. Synthesis of (9Z)-9,13-tetradecadien-11-ynal.
7. 2-(9-Decynyloxy)-tetrahydropyran 2 was prepared from 8-chloro-octan-1-ol in
2.5 equiv of vinyl acetylene in pyrrolidine at 0 °C resulted in com-
plete consumption of the starting material, yielding the pure dien-
yne 5 in 81% isolated yield.10 The synthesis was completed by
straightforward removal of the THP-protecting group (PTSA in
MeOH; 90% purified yield), and pyridinium chlorochromate oxida-
tion of the resulting alcohol 6 to yield the target aldehyde 1
(71%).11 This short and efficient synthesis is now under commercial
development to produce the pheromone for use throughout Cen-
tral America, South America, and California.
two steps.
DHP, PTSA
Et2O
Cl
Li
Cl
OH
OTHP
C
C
H.EDA, NaI (cat.)
DMSO
OTHP
2, 65% for 2 steps
8. Hutzinger, M. E.; Oehlschlager, A. C. J. Org. Chem. 1995, 60, 4595–4601.
9. Denmark, S. E.; Wang, Z. Org. Synth. 2004, 81, 42–53.
10. (9Z)-Tetradeca-9,13-dien-11-yn-1-ol (6): A dry two-necked flask under Ar was
loaded with bis(triphenyl-phosphine)palladium(II) dichloride (0.069 g,
0.098 mmol), CuI (0.037 g, 0.19 mmol), and pyrrolidine (5 mL), and the
Acknowledgments
mixture was cooled to 0 °C. Iodide
4 (1.43 g, 3.91 mmol) in pyrrolidine
We thank the California Avocado Commission and the Hansen
Trust for financial support of this work.
(3 mL) was added dropwise, followed by dropwise addition of 1-buten-3-yne
(1.24 g of a 41.1% xylene solution, 9.79 mmol; GFS Chemicals, Powell, OH). The
reaction mixture was stirred for 3 h while gradually warming to room
temperature, then poured into ice-cold 1 M KH2PO4 solution and extracted
with hexanes. The combined organic layer was washed with water and brine,
dried, and concentrated. The crude product was purified by flash
chromatography on silica gel (hexanes/Et2O = 95/5) to give 0.92 g (81%) of 2-
(tetradeca-9,13-dien-11-yn-1-yloxy)tetrahydro-2H-pyran 5 as a light yellow
oil, which was dissolved in MeOH (8 mL) and stirred with PTSA (0.030 g,
0.16 mmol) for 2.5 h. The mixture was diluted with hexanes, washed with
saturated aqueous NaHCO3 and brine, then dried and concentrated. The crude
product was purified by vacuum flash chromatography on silica gel (hexanes/
EtOAc = 9/1 to 5/1) to give 0.59 g (90%) of 6 as a colorless oil. The 1H NMR
spectrum was consistent with that described previously.3
References and notes
1. (a) Ebeling, W. Subtropical Fruit Pests. Division of Agricultural and Natural
Resources, University of California, Berkeley; 1959.; (b) Boscan de Martinez, N.;
Godoy, F. J. Agron. Trop. 1985, 34, 205–208; (c) Miller, C. E.; Green, A. S.;
Harabin, V.; Stewart, R. D. Risk analysis of a systems approach for Mexican
avocados. US Dept. of Agriculture-Animal and Plant Health Inspection Service,
Riverdale MD; 1995.; (d) Ventura, M. U.; Destro, D.; Lopes, E. C. A.; Montalvan,
R. Fl. Entomol. 1999, 82, 625–631.
2. Miller, C. E. 1995. Risk Management Analysis: A Systems Approach for Mexican
Avocado. Animal and Plant Health Inspection Service, US Dept. of Agriculture,
Riverdale, MD.
3. Millar, J. G.; Hoddle, M.; McElfresh, J. S.; Zou, Y.; Hoddle, C. Tetrahedron Lett.
2008, 49, 4820–4823.
4. Hoddle, M. S.; Millar, J. G.; Hoddle, C. D.; Zou, Y.; McElfresh, J. S. J. Econ. Entomol.
2009, 102, 1460–1467.
5. Wu, Y.-T.; Noltemeyer, M.; de Meijere, A. Eur. J. Org. Chem. 2005, 2802–2810.
6. With 2 equiv of 1-buten-3-yne (41.1 wt % in xylene), the product was obtained
in moderate yield with some unreacted starting material.
11. Spectral data for (9Z)-9,13-tetradecadien-11-ynal (1): 1H NMR:
d 9.75 (t,
J = 2.0 Hz, 1H), 5.92 (m, 2H), 5.60 (dd, J = 17.6, 2.4 Hz, 1H), 5.56 (dd, J = 11.2,
1.6 Hz, 1H), 5.45 (dd, J = 11.2, 1.6 Hz, 1H), 2.41 (td, J = 7.4, 2.0 Hz, 2H), 2.30 (qd,
J = 7.3, 1.6 Hz, 2H), 1.62 (m, 2H), 1.44–1.28 (m, 8H). 13C NMR: d 203.0 (CH),
144.4 (CH), 126.2 (CH2), 117.6 (CH), 109.1 (CH), 92.4 (C), 87.2 (C), 44.1 (CH2),
30.4 (CH2), 29.3 (CH2), 29.2 (CH2), 29.0 (CH2), 28.8 (CH2), 22.2 (CH2). IR (neat):
3018, 2928, 2856, 2719, 1724, 1599, 1464, 1414, 1392, 1164, 971, 917, 738,
. HRMS (ESI/APCI) calcd for C14H21O
674 cmÀ1 [M+H]+: 205.1592, found
205.1589.