Copper-catalyzed cross-coupling of (Z)-allyl phenyl ethers with Grignard compounds in the synthesis of insect pheromones

Article abstract of DOI:10.1134/S1070363208100125

(8Z)-Dodec-8-en-1-yl acetate (pheromone of oriental fruit moth Grapholita molesta) and (9Z)-dodec-9-en-1-yl acetate (pheromone of grape berry moth Paralobesia viteana) containing impurities of isomeric structures were synthesized via copper-catalyzed cross-coupling of (Z)-1-phenoxyhex-2-ene and (Z)-1-phenoxypent-2-ene, respectively, with Grignard compounds in the key stage.

Full text of DOI:10.1134/S1070363208100125

ISSN 1070-3632, Russian Journal of General Chemistry, 2008, Vol. 78, No. 10, pp. 1897–1899. © Pleiades Publishing, Ltd., 2008.
Original Russian Text © E.A. Petrushkina, V.N. Kalinin, 2008, published in Zhurnal Obshchei Khimii, 2008, Vol. 78, No. 10, pp. 1659–1661.
Copper-Catalyzed Cross-Coupling of (Z)-Allyl Phenyl Ethers
with Grignard Compounds in the Synthesis of Insect Pheromones
E. A. Petrushkina and V. N. Kalinin
Nesmeyanov Institute of Organometallic Compounds, Russian Academy of Sciences,
ul. Vavilova 28, Moscow, 119991 Russia
e-mail: petrushkina@rambler.ru
Received October 25, 2007
Abstract— (8Z)-Dodec-8-en-1-yl acetate (pheromone of oriental fruit moth Grapholita molesta) and (9Z)-
dodec-9-en-1-yl acetate (pheromone of grape berry moth Paralobesia viteana) containing impurities of
isomeric structures were synthesized via copper-catalyzed cross-coupling of (Z)-1-phenoxyhex-2-ene and (Z)-
1-phenoxypent-2-ene, respectively, with Grignard compounds in the key stage.
DOI: 10.1134/S1070363208100125
Copper-catalyzed cross-coupling of allyl com-
pounds with Grignard reagents provides a useful tool
for building up carbon–carbon bond [1]. We previously
showed that this procedure ensures highly selective
preparation of pheromones having an E-alkene moiety
from (2E)-1-phenoxyocta-2,7-diene [2, 3]. However,
isomerization of Z-double bond in the synthesis of
some conjugated diene alcohols and acetates has also
been reported [4, 5]. We made an attempt to effect
copper-catalyzed cross-coupling of Z-alkenyl phenyl
ethers with an isolated double bond with a view to
obtain known (8Z)- and (9Z)-dodecenyl acetates I and
II that are pheromones of Lepidoptera insects, oriental
fruit moth Grapholita molesta [6] and grape berry
moth Paralobesia viteana [7], respectively (Sche-
me 1).
The required hydrocarbon chains containing a Z-
configured double bond were built up by reacting (Z)-
1-phenoxyhex-2-ene (IIIa) and (Z)-1-phenoxypent-2-
ene (IIIb) (Scheme 1) with the Grignard compounds
obtained from 6-bromohexan-1-ol and 7-chloroheptan-
1-ol (which were preliminarily protected at the
hydroxy group). The reactions were carried out in the
presence of Li2CuCl4 as catalyst. The latter is rapidly
reduced in situ to copper(I) salt (CuCl·2LiCl) by the
action of Grignard compound [8, 9]. The mechanism
of this reaction remains a matter of extensive
discussions. Up to now, two main reaction paths have
been proposed [10–12]. The first of these involves
intermediate π-allyl CuIII complexes and leads to the
formation of three products: cis- and trans-isomeric α-
substitution products and γ-substitution product. The
Scheme 1.
(1) BrMg(CH2)6OSiMe3, Li2CuCl4
OAc
OPh
R
(2) HCl, EtOH
(3) AcCl, AcOH
IIIa, IIIb
I
O
O
(1) ClMg(CH2)7
(2) AcCl, AcOH
, Li2CuCl4
OAc
II
III, R = Pr (a), Et (b).
1897

1898
PETRUSHKINA, KALININ
second path implies direct replacement in intermediate
σ-allyl CuI complexes to give only two products: α-
substitution product with the same geometry of the
double bond and γ-substitution product. Conditions
ensuring selective substitution at the α- or γ-position
were found, and structural factors in the substrate
responsible for the reaction direction were determined
[10–12]. In keeping with published data on the use of
the above reaction in the synthesis of natural
compounds, trans-configured double bond as a rule
does not change during the process, while cis-double
bond may undergo isomerization or not depending on
the substrate structure. The presence of a conjugated
system favors isomerization of Z-double bond [4, 5,
13, 14], whereas in the alkylation with dialkylcuprates
(LiCuMe2) of allyl carboxylates with an isolated
double bond, in particular geranyl or neryl acetates, the
corresponding α-substituted derivatives are formed
without change in the double bond configuration [15].
As allylating agents we used phenyl ethers in which
the departing group is inactive. In this case the
corresponding α-substituted products are formed
preferentially [11, 12]. To a solution of Li2CuCl4 and
compound IIIa or IIIb in THF, cooled to –20°C, a
solution of the corresponding Grignard reagent in THF
was quickly added to exclude formation of γ-
substituted product. The Grignard reagents were
prepared from 6-bromo-1-trimethylsilyloxyhexane
[16] and acetaldehyde 6-chloroheptyl ethyl acetal [17].
To reduce the number of steps in the synthesis of
compound II, the hydroxy group in 7-chloroheptan-1-
ol was protected by conversion into mixed acetal,
taking into account that the subsequent reaction of the
acetal with acetyl chloride in acetic acid could directly
produce the desired acetate. However, the
transformation of the acetal into acetate II required
severe conditions, heating in boiling acetic acid.
Compounds I and II were formed with different
selectivities. Compound I was isolated as a single
isomer which was identified by GLC using an
authentic sample. In the synthesis of II, the acetylation
stage gave a mixture of three isomers at a ratio of
1:15:2, the major isomer being the target product
(GLC). Predominant formation of the α-substituted
products in the synthesis of I and II indicates that the
reaction involves mainly CuI complexes as
intermediates. The presence of an insignificant amount
of the trans isomer of II implies some contribution of
the reaction path involving intermediate CuIII
complexes. Thus the selectivity of copper-catalyzed
cross-coupling of alkenyl phenyl ethers with alkyl
Grignard compounds is determined not only by
reaction conditions but also by the structure of both
reactants. Presumably, C6+C6 alkyl chain coupling is
preferred to C5+C7.
Esters IIIa and IIIb were synthesized according to
Scheme 2, via transformation of prop-2-yn-1-yl bro-
mide into 3-phenoxyprop-1-yne (V) [18], alkylation of
the latter with propyl bromide or ethyl iodide, and
subsequent reduction of the triple bond in ethers VIa
and VIb with hydrogen over Lindlar catalyst poisoned
with quinoline.
In the synthesis of compound I, the hydroxy group
was protected via conversion into trimethylsiloxy
group which was readily removed by heating in boiling
ethanol. The subsequent treatment with acetyl chloride
in acetic acid at 40°C gave the corresponding acetate.
Scheme 2.
(1) NaNH2
H2
(2) PrBr or EtI
PhONa
CH
CCH2Br
CH
CCH2OPh
RC
CCH2OPh
IIIa, IIIb
[Pd]
V
VIa, VIb
R = Pr (a), Et (b).
column, 2000×3 mm, packed with 15% of SKTFT-50
on Chromaton N-AW; carrier gas helium. The IR
spectra were recorded from thin films on an UR-20
spectrometer.
EXPERIMENTAL
The reagents used had a purity of 99%; solvents
and liquid reagents were distilled prior to use and were
stored under argon. All reactions were carried out
under argon. GLC analysis was performed on an
LKhM-8MD (5) chromatograph equipped with a steel
1-Phenoxyhex-2-yne (VIa). 3-Phenoxyprop-1-yne
(V), 22.7 g, was treated with an equimolar amounr of
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 78 No. 10 2008

COPPER-CATALYZED CROSS-COUPLING OF (Z)-ALLYL PHENYL ETHERS
1899
metallic sodium in 150 ml of liquid ammonia at –60 to
–63°C. The resulting sodium derivative was alkylated
with 21.2 g of propyl bromide at –40 to –45°C. Yield
12.3 g (41%), bp 80°C (1 mm Hg). Found, %: C 82.21;
H 8.07. C12H14O. Calculated, %: C 82.71; H 8.09.
poured into dilute hydrochloric acid, the organic phase
was separated and dried over Na2SO4, the solvent
(THF) was distilled off under reduced pressure, the
residue was diluted with hexane and washed with a
solution of sodium hydroxide, and the hexane layer
was dried over Na2SO4 and evaporated to obtain 4.5 g
(76%) of (Z)-12-[1-(ethoxy)ethoxy]dodec-3-ene. The
product was mixed with 1.7 g of acetyl chloride and 24 g
of glacial acetic acid, and the mixture was heated for
4 h at 40°C and then heated for 3 h under reflux.
Analysis by GLC showed the presence of three
compounds.
(Z)-1-Phenoxyhex-2-ene (IIIa). Compound VIa,
6.57 g, was hydrogenated at room temperature over
Lindlar catalyst poisoned with 1 ml of quinoline. Yield
6.62 g (99%), bp 125–127°C (12 mm Hg). Found, %:
C 82.00; H 9.09. C12H16O. Calculated, %: C 81.77; H
9.15.
1-Phenoxypent-2-yne (VIb) was synthesized as
described above for compound VIa from 32.18 g of
ether V and 31.3 g of ethyl iodide. Yield 16.31 g
(42%), bp 115–116°C (8 mm Hg). Found, %: C 82.72;
H 7.49. C11H12O. Calculated, %: C 82.46; H 7.55.
REFERENCES
1. Knochel, P. and Betzemeier, B., Modern Organocopper
Chemistry, Krause, N., Ed., Weinheim: Wiley, 2002, p. 45.
2. Zakharkin, L.I. and Petrushkina, E.A., Izv. Akad. Nauk
SSSR, Ser. Khim., 1982, no. 5, p. 1181.
3. Zakharkin, L.I. and Petrushkina, E.A., Russ. J. Org.
Chem., 1982, vol. 18, no. 8, p. 1623.
4. Descoins, C.E. and Henrick, C.A., Tetrahedron Lett.,
1972, vol. 13, no. 30, p. 2999.
5. Gassani, G., Massardo, P., and Piccardi, P., Tetrahedron
Lett., 1980, vol. 21, no. 36, p. 3497.
6. Holman, G. and O’Keefe, D.F., Tetrahedron Lett., 1973,
vol. 14, no. 9, p. 673.
7. Roelofs, W.L., Tette, J.P., Taschenberg, E.F., Comeau, A.,
Insect Physiol., 1971, vol. 17, no. 12, p. 2235.
8. Tamura, M. and Kochi, J.K., Synthesis, 1971, no. 4,
p. 303.
9. Kochi, J.K., Organometallic Mechanisms and Catalysis,
New York: Academic, 1978, p. 381.
10. Karlström, A.S.E. and Bäckvall, J.-E., Chem. Eur. J.,
2001, vol. 7, no. 9, p. 1981.
(Z)-1-Phenoxypent-2-ene (IIIb). Hydrogenation of
16.31 g of compound VIb in 90 ml of hexane over 1 g
of Lindlar catalyst poisoned with 1 ml of quinoline
gave 11.54 g (68%) of Z-alkene IIIb with bp 116–117°C
(23 mm Hg). Found, %: C 81.21; H 8.49. C11H14O.
Calculated, %: C 81.44; H 8.70.
(8Z)-Dodec-8-en-1-yl acetate (I). The Grignard
compound prepared from 3.9 g of 1-bromo-6-
trimethylsiloxyhexane in 10 ml of THF was added at
–20°C to a solution of 2.5 g of phenoxyalkene IIIa and
0.6 g of Li2CuCl4 in 20 ml of THF, and the mixture
was stirred for 2 h at –5 to 0°C. The solvent was
distilled off, 50 ml of 80% ethanol was added to the
residue, the mixture was heated for 1 h under reflux,
0.4 ml of concentrated hydrochloric acid was added,
and the mixture was stirred for 8 h at 20°C, diluted
with 30 ml of water, and extracted with diethyl ether.
The extract was dried over MgSO4 and evaporated,
and the residue was distilled under reduced pressure.
Yield of (8Z)-dodec-8-en-1-ol 2.1 g (81%), bp 88–90°C
(1 mm Hg). IR spectrum, ν, cm–1: 1660 (C=C); 1520,
1615 (C=Carom); 2960, 2990, 3070 br (C–Harom); 3440
(NH); 700 (δC=CH2). Found, %: C 77.72; H 12.80.
C12H24O. Calculated, %: C 78.19; H 13.13. The
product was converted into acetate I according to
standard procedure (Ac2O, AcOH).
11. Bäckvall, J.-E., Selén, M., and Grant, B., J. Am. Chem.
Soc., 1990, vol. 112, no. 19, p. 6615.
12. Bäckvall, J.-E. and Sellén, M., J. Chem. Soc., Chem.
Commun., 1987, no. 11, p. 827.
13. Goering, H.L. and Kantner, S.S., J. Org. Chem., 1983,
vol. 48, no. 5, p. 721.
14. Samain, D., Descoins, C.E., and Langlois, J., Nouv. J.
Chim., 1978, vol. 2, no. 3, p. 249.
15. Levisalles, J., Rudler-Chauvin, M., and Rudler, H., J.
Organomet. Chem., 1977, vol. 136, no. 1, p. 103.
(Z)-Dodec-9-en-1-yl acetate (II). The Grignard
compound prepared from 5.2 g of 7-chloro-1-[1-
(ethoxy)ethoxy]heptane in 20 ml of THF was added at
–20°C to a solution of 3.7 g of phenoxyalkene IIIb and
0.99 g of Li2CuCl4 in 20 ml of THF, and the mixture
was stirred for 2 h at –5 to 0°C. The mixture was then
16. Mattes, H. and Benezra, C., J. Org. Chem., 1988, vol. 53,
no. 12, p. 2732.
17. Caplin, J. and Tyman, J.H.P., J. Chem. Res., Miniprint,
1982, no. 1, p. 321.
18. Gaudemar, P.M., Ann. Chim., 1956, vol. 13, no. 1, p. 161.
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