Stereospecific synthesis of all four isomeric 6,8-heneicosadien-11-ones: Sex pheromone components of the painted apple moth Teia anartoides

Article abstract of DOI:10.1016/j.tetlet.2004.08.095

All four isomeric 6,8-heneicosadien-11-ones were synthesised using a Suzuki-coupling strategy.

Full text of DOI:10.1016/j.tetlet.2004.08.095

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 7651–7654
Stereospecific synthesis of all four isomeric
6,8-heneicosadien-11-ones: sex pheromone components of
the painted apple moth Teia anartoides
Daniel J. Comeskey,a Barry J. Bunna,* and Simon Fielderb
aHortResearch, Tennet Drive, Private Bag 11030, Palmerston North, New Zealand
bSilverbrook Research Pty Ltd, Unit C, 6-8 Lyon Park Road, North Ryde 2113, Sydney, Australia
Received 5 July 2004; revised 10 August 2004; accepted 17 August 2004
Abstract—The stereospecific synthesis of all four isomeric 6,8-heneicosadien-11-ones, sex pheromone components of the painted
apple moth, Teia anartoides, is reported using the Suzuki-coupling of vinyl boronic acid and vinyl iodide intermediates.
ꢀ 2004 Elsevier Ltd. All rights reserved.
The painted apple moth Teia anartoides1 occurs natu-
rally in the south-eastern States of Australia but was
accidentally introduced to New Zealand in 1999 where
it poses a significant threat to the native fauna as well
as to commercial plant species. The potential economic
cost of this pest prompted the New Zealand government
to initiate a spray campaign to eradicate the insect. As
part of an ongoing study into the monitoring the popu-
lation and spread of this pest, we became interested in
identifying its sex pheromone. Previously, 6Z,8E-hene-
icosadien-11-one 1 has been reported as one component
of a complex pheromone blend.2,3 In an effort to identify
further unknown components, we decided to synthesise
the other possible isomers of 6,8-heneicosadien-11-ones.
Catecholborane was reacted with 1-heptyne at 70ꢁC to
give boronic acid 9 in 55% yield as an off-white solid.5
Boronic acid 9 was readily converted to E-1-iodohept-
1-ene 8 by reaction with iodine in the presence of base,6
while Z-1-iodohept-1-ene 7 was obtained by addition of
iodine to a solution of boronic acid 9 in a mixture of
THF and Et2O7 (Scheme 2). Both these iodides were
somewhat light sensitive.
Preparation of 6Z,8Z-heneicosadien-11-one 4 requires
access to Z-heptenylboronic acid 10. Thus, 1-heptyne
was converted to 1-bromo-1-heptyne using NBS and
catalytic AgNO3 in acetone.8 Subsequent treatment with
HBBr2 DMS complex followed by potassium triisoprop-
oxyborohydride and then methanol (Scheme 3) afforded
the Z-heptenylboronic acid 10 as a viscous oil.9
To prepare all four isomers of 6,8-heneicosadien-11-one
(1, 2, 3 and 4), we needed a route that was diastereospe-
cific and gave swift access to reasonable quantities of
material for wind-tunnel and field testing. We decided
on a Suzuki-coupling4 strategy as one, which would uti-
lise some common intermediates and thus be more effi-
cient in cost and time. This required access to C7
iodides 7 and 8 and boronic acids 9 and 10, as well as
the C14 boronic acid 5 and C14 iodide 6. The proposed
syntheses of all the isomers by this method are illus-
trated in Scheme 1.
Starting from epoxydodecane, ring opening with lithium
acetylide–EDA complex afforded tetradec-1-yn-4-ol
11.2,10 Treatment of tetradec-1-yn-4-ol 11 with cate-
cholborane gave E-tetradec-1-en-4-ol-1-boronic acid
12, which in turn could be readily converted to Z-1-
iodotetradec-1-en-4-ol 13 by reaction with I2 in THF
and Et2O (Scheme 4).
With access to all intermediates needed to prepare the
target dienes, we now investigated the Suzuki-coupling
reaction. Treatment of a mixture of the boronic acid
12 with each of the iodides 7 and 8 with tetrakis-triphen-
ylphosphine palladium(0) followed by 2equiv of base
(NaOEt) and heating to 70ꢁC in benzene, gave reasona-
bly clean conversion to the dienes 14 and 15. GCMS and
Keywords: 6,8-Heneicosadien-11-ones; Sex pheromone; Painted apple
moth.
*
Corresponding author. Tel.: +64 6 356 8080 7798; fax: +64 6 351
7004; e-mail: bjbunn@hotmail.com
0040-4039/$ - see front matter ꢀ 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.08.095

7652
D. J. Comeskeyet al. / Tetrahedron Letters 45 (2004) 7651–7654
O
I
(i),(ii)
9
4
OH
4
1
7
8
B(OH)2
+
O
9
(i),(ii)
(i),(ii)
5
I
4
4
9
O
2
3
B(OH)2
4
OH
4
4
9
9
+
I
B(OH)2
9
O
(i),(ii)
6
4
9
4
10
Scheme 1. Proposed syntheses of 6,8-heneicosadien-11-one isomers by Suzuki-coupling. Reagents and conditions: (i) Pd(PPh3)4, NaOEt; (ii) Dess–
Martin periodinane.
I
4
(ii)
(i)
8
7
B(OH)2
I
4
4
(iii)
9
4
Scheme 2. Preparation of E-1-iodohept-1-ene, Z-1-iodohept-1-ene and E-hept-1-enyl-1-boronic acid. Reagents and conditions: (i) catecholborane
70ꢁC (55%); (ii) Et2O, NaOH, I2 (53%); (iii) Et2O, THF, I2 (37%).
B(OH)2
Br
(i)
(ii)
4
4
4
10
Scheme 3. Preparation of Z-hept-1-enyl-1-boronic acid. Reagents and conditions: (i) AgNO3, acetone, NBS (46%); (ii) HBBr2 then KIPBH (78%).
OH
OH
OH
O
(ii)
(iii)
(i)
B(OH)2
I
9
9
9
9
12
11
13
Scheme 4. Preparation of E-tetradec-1-en-4-ol-1-boronic acid and Z-1-iodotetradec-1-en-4-ol. Reagents and conditions: (i) lithium acetylide–EDA
complex, DMSO (82%); (ii) catecholborane, 70ꢁC (29%); (iii) Et2O, THF, I2 (46%).
NMR analysis of the dienes showed that the stereo-
chemical integrity of the starting materials had been pre-
served in the product.
The final step in the synthesis was to oxidise the alcohols
to the ketones. Previously, chromium(VI)9 and the Dess-
Martin periodinane11 have been used to prepare 1. A typi-
cal reaction using chromium(VI) needed several hours
for completion, whereas use of the Dess–Martin reagent
gave rapid conversion to the ketone in good yield with no
side products.14 In particular, we found the 6Z,8Z-iso-
mer 4 to be degraded during the course of an oxidation
using chromium(VI). We now had a reliable method,
which gave access to all four 6,8-heneicosadien-11-ones.
Despite the low yields overall, particularly in the case of
The coupling reactions between Z-1-iodotetradec-1-en-
4-ol 13 and the two C7 boronic acids 9 and 10 did
not, however, proceed as cleanly as hoped. In both
cases, separation of the product from side-products
was troublesome, and in the case of the 6Z,8Z-isomer
the yield was only 8%. The results of all the coupling
reactions are summarised in Table 1.13

D. J. Comeskeyet al. / Tetrahedron Letters 45 (2004) 7651–7654
Table 1. Suzuki-coupling reactions between C14 boronic acids and C7 iodides
7653
C14 fragment
C7 fragment
Product
OH
Yield/%
OH
I
B(OH)2
B(OH)2
36
4
4
9
9
7
12
14
OH
OH
OH
OH
OH
I
66
40
8
4
8
9
9
9
9
4
12
15
16
17
B(OH)2
4
I
I
4
4
9
9
9
13
13
OH
B(OH)2
4
10
Table 2. Oxidation of 6,8-heneicosadien-11-ols to 6,8-heneicosadien-11-ones using Dess–Martin periodinane
Dienol
OH
Dienone
Yield/%
72
O
4
4
9
9
14
15
16
17
2
1
3
4
OH
OH
O
66
64
78
9
9
4
4
O
4
4
4
4
9
9
OH
O
9
9
2. Jury, J.; Fielder, S.; Vigneswaran, M. Tetrahedron Lett.
2003, 44, 27–28.
the 6Z,8Z-isomer, we were able to prepare sufficient
quantities of all compounds to carry out extensive
wind-tunnel and field testing12 (Table 2).
3. Gries, G.; Slessor, K. N.; Khaskin, G.; Priyantha, D. C.;
Wimalaratne, P. D. C.; Gray, T. D.; Grant, G. G.; Tracey,
A. S.; Hulme, M. J. Chem. Ecol. 1997, 23, 19–34.
4. Miyaura, M.; Suzuki, A. Chem. Commun. 1979,
866.
In summary, we have synthesised all four isomeric 6,8-
heneicosadien-11-ones from readily accessible interme-
diates using 4 Suzuki-coupling reactions.
5. Brown, H. C.; Gupta, S. K. J. Am. Chem. Soc. 1972, 94,
4370–4371.
Acknowledgements
6. Brown, H. C.; Hamaoka, T.; Ravindran, N. J. Am. Chem.
Soc. 1973, 95, 5786–5788.
7. Brown, H. C.; Subrahmanyam, C.; Hamaoka, T.; Ravin-
dran, N.; Bowman, D.; Misumi, S.; Unni, M.; Somayaji,
V.; Bhat, N. J. Org. Chem. 1989, 54, 6068–6075.
8. Hofmeister, H.; Annen, K.; Laurent, H.; Wiechert, R.
Angew. Chem., Int. Ed. Engl. 1984, 23, 727–728.
9. Brown, H. C.; Imai, T. Organometallics 1984, 3, 1392–
1395.
This work was carried out with the financial support of
MAF, New Zealand. We would also like to thank Dr.
Pat Edwards of Massey University for NMR support
and Adam Matich and Martin Hunt of HortResearch
for help with mass spectra.
References and notes
10. Buist, P.; Adeney, R. J. Org. Chem. 1991, 56, 3449–
3452.
1. Common, I. F. B. Moths of Australia; Melbourne
University Press, ISBN 0522843263, 1990.
11. Dess, D. B.; Martin, J. C. J. Org. Chem. 1983, 48, 4155–
4156.

7654
D. J. Comeskeyet al. / Tetrahedron Letters 45 (2004) 7651–7654
12. The pheromone components synthesised in this paper
have been utilised in field and wind-tunnel testing. El-
Sayed, A. J. Chem. Ecol., in press.
J = 6.8Hz); 13C NMR (CDCl3, 100MHz) 136.3, 131.9,
125.3, 124.8, 71.6, 36.9, 35.8, 32.9, 31.9, 31.5, 29.7, 29.6,
29.6, 29.6, 29.4, 29.0, 25.8, 22.7, 22.5, 14.1, 14.0ppm.
14. Experimental details and selected data for compounds 1–
4. Preparation of 6Z,8E-heneicosadien-11-one. Dess–Mar-
tin periodinane (671mg, 1.63mmol) was added to solution
of 6Z,8E-heneicosadien-11-ol (180mg, 0.58mmol) in
CH2Cl2 (12mL) at room temperature. After 1h, NaHCO3
(10mL, satd aq) was added. The aqueous phase was
extracted with CH2Cl2 (3 · 10mL) and the combined
organics were dried over MgSO4. Column chromatogra-
phy using 5% EtOAc/95% petroleum ether as the eluant
gave compound 1 as a colourless oil. 119mg, 66%.
Spectral data were consistent with those reported in the
literature.2,3 6E,8E-Heneicosadien-11-one: 72%. Found M+
13. Experimental details and selected data for compounds 14–
17. Preparation of 6Z,8E heneicosadien-11-ol. A mixture of
E-tetradec-1-en-4-ol-1-boronic acid (250mg, 0.97mmol)
and Z-1-iodohept-1-ene (237mg, 1.06mmol) was stirred in
dry benzene (3.9mL) at room temperature under N2.
Tetrakis-triphenylphosphine palladium (56mg, 0.046
mmol) was added, immediately followed by NaOEt
(0.97mL of a 2M solution in EtOH, 1.94mmol). The
reaction mixture was heated to 70ꢁC for 45min. After
cooling to room temperature, Et2O (15mL) was added
followed by water (10mL). The aqueous phase was
extracted with Et2O (3 · 10mL) and the combined organ-
ics dried over MgSO4. The solvent was removed in vacuo.
Column chromatography using 5% EtOAc/95% petroleum
ether as the eluant gave compound 15 as a colourless oil.
158mg, 53%. NMR data were consistent with those
reported in the literature.2,3 6E,8E-Heneicosadien-11-ol:
36%. Found M+ÀH2O 290.2975, requires 290.2974; 1H
NMR (CDCl3, 400MHz) 6.04–5.98 (2H, m), 5.66–5.53
(2H, m), 3.62 (1H, br), 2.20–2.00 (4H, m), 1.50–1.20 (24H,
m), 0.90–0.70 (6H, m) ppm; 13C NMR (CDCl3, 100MHz)
134.2, 134.2, 130.2, 127.6, 71.5, 41.1, 37.2, 32.9, 32.2, 31.7,
30.0, 30.0, 30.0, 30.0, 29.3, 26.0, 22.3, 22.8, 14.4, 14.3ppm.
6Z,8Z-Heneicosadien-11-ol: 8%. Found M+ÀH2O
290.2983, requires 290.2974; 1H NMR (CDCl3,
400MHz) 6.42 (1H, dd, J = 11.3, 7.6Hz), 6.24 (1H, m),
5.52–5.47 (2H, m), 3.65 (1H, d, J = 6Hz), 2.35 (2H, m),
2.17 (2H, m), 1.50–1.20 (24H, m), 0.88 (3H, t, J = 6.4Hz),
0.87 (3H, t, J = 7.2Hz) ppm; 13C NMR (CDCl3, 100MHz)
133.8, 127.3, 127.0, 123.6, 72.0, 37.3, 35.9, 32.3, 31.9, 30.0,
29.7, 29.6, 29.6, 29.6, 29.6, 27.9, 26.1, 23.0, 22.9, 14.5,
14.4ppm. 6E,8Z-Heneicosadien-11-ol: 40%. Found
1
306.2924, requires 306.2923; H NMR (CDCl3, 400MHz)
6.10–5.99 (2H, m), 5.74–5.59 (2H, m), 3.15 (2H, d,
J = 7.2Hz), 2.42 (2H, t, J = 7.4Hz), 2.06 (2H, m), 1.70–
1.60 (2H, m), 1.40–1.20 (20H, m), 0.89 (3H, t, J = 6.6Hz),
0.88 (3H, t, J = 6.7Hz); 13C NMR (CDCl3, 100MHz)
209.3, 134.7, 134.2, 129.6, 122.8, 46.7, 42.3, 32.5, 31.9,
31.4, 29.5, 29.4, 29.4, 29.3, 29.2, 28.9, 23.7, 22.6, 22.5, 14.1,
14.0ppm. 6E,8Z-Heneicosadien-11-one: 64%. Found M+
1
306.2931, requires 306.2923; H NMR (CDCl3, 400MHz)
6.24–6.09 (2H, m), 5.78–5.71 (1H, m), 5.48–5.42 (1H, m),
3.26 (2H, dd, J = 7.5, 1.2Hz), 2.43 (2H, t, J = 7.3Hz), 2.11
(2H, m), 1.70–1.60 (2H, m), 1.50–1.30 (20H, m), 0.88 (3H,
t, J = 6.8Hz), 0.87 (3H, t, J = 6.8Hz) ppm; 13C NMR
(CDCl3, 100MHz) 208.9, 137.1, 131.7, 124.8, 120.0, 42.3,
42.0, 32.0, 31.9, 31.4, 29.5, 29.4, 29.4, 29.3, 29.2, 28.9, 23.8,
22.7, 22.5, 14.1, 14.0ppm. 6Z,8Z-Heneicosadien-11-one:
78%. Found M+ 306.2920, requires 306.2923; 1H NMR
(CDCl3, 400MHz) 6.44 (1H, m), 6.17 (1H, m), 5.61–5.54
(2H, m), 3.29 (2H, dd, J = 7.5, 1.4Hz), 2.43 (2H, t,
J = 7.5Hz), 2.17 (2H, m), 1.60–1.40 (2H, m), 1.50–1.20
(20H, m), 0.88 (3H, t, J = 6.8Hz), 0.88 (3H, t, J = 6.2Hz)
ppm; 13C NMR (CDCl3, 100MHz) 208.8, 134.3, 126.5,
122.8, 122.1, 42.4, 41.7, 31.9, 31.4, 29.5, 29.4, 29.4, 29.3,
29.2, 27.5, 23.8, 22.6, 22.5, 14.1, 14.0ppm.
1
M+ÀH2O 290.2973, requires 290.2974; H NMR (CDCl3,
400MHz) 6.30 (1H, m), 6.12 (1H, m), 5.71 (1H, m), 5.33
(1H, m), 3.64 (1H, br), 2.33 (2H, m), 2.10 (2H, m), 1.50–
1.20 (24H, m), 0.88 (3H, t, J = 6.8Hz), 0.87 (3H, t,