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J . Org. Chem. 1998, 63, 3806-3807
Sch em e 1
Efficien t P r ep a r a tion of F u n ction a lized (E,Z)
Dien es Usin g Acetylen e a s th e Bu ild in g Block
Zhong Wang, Xiyan Lu,* Aiwen Lei, and Zhaoguo Zhang
Shanghai Institute of Organic Chemistry, Chinese Academy of
Sciences, 354 Fenglin Lu, Shanghai 200032, China
Received March 10, 1998
(E,Z)-Diene structures spread widely in the scope of not
only important bioactive natural products,1 but also useful
chemicals applicable in the perfume industry and other
fields.2 The characteristic (E,Z) double-bond configuration
of the molecules, which is usually responsible for the special
functions,3 meanwhile poses great challenges for their
stereoselective synthesis. The advent solutions mainly
reside in the range of Wittig-type olefination4 or transition-
metal-mediated coupling reactions of deliberately function-
alized precursors.5 While the methods of both classes have
been successfully used in a good number of laboratory
syntheses, their intrinsic drawback of low atom economy
causing poor mass conversion greatly limited their applica-
tion in large-scale preparations.
Sch em e 2
Sch em e 3
Sch em e 4
A naive retrosynthetic analysis suggests that two acety-
lene molecules can be added together to form the (E,Z)
double bonds, provided the addition reaction occurs in a
stereoselective manner. Indeed, from the well-documented
organometallic elementary reactions, we could infer that a
tandem addition incorporating two molecules of acetylene
may lead to (E,Z)-conjugated diene structure (Scheme 1).
In this sequence, the stereochemical requirements of
trans-addition and cis-insertion (carbometalation) helped to
establish the otherwise hard-to-access conjugate (E,Z) double-
bond configuration. Despite the extreme efficiency this
sequence may bring about, there was only one precedent in
the literature realizing such a concept: The Pd-catalyzed
cotrimerization reaction of acetylene and allyl chloride
developed by Kaneda et al.,6 but the reaction gave in low
yield a mixture of codimer and cotrimer and the stereochem-
istry of the cotrimer was not established (Scheme 2).
Recently, we have developed the facile synthesis of γ,δ-
unsaturated carbonyl compounds in which a halide-assisted
protonolysis efficiently recycles Pd(II)-catalytic species,7 thus
effecting the tandem addition reaction of halide, an alkyne,
and an R,â-unsaturated carbonyl. In this context, we
attempted the reaction of acetylene with R,â-unsaturated
electron-deficient alkenes in the presence of palladium
catalyst to explore the possibility of developing new methods
for (E,Z)-diene synthesis.
to avoid the excessive polymerization of acetylene. When
acetylene was passed through a mixture of acrolein 1 (20
mL), HOAc (50 mmol), Pd(OAc)2 (0.5 mmol), and LiBr (5
mmol) at 15 °C for 2 h, rapid formation of palladium black
was observed. The reaction afforded the expected dienal 2a
together with the R,â-unsaturated trienal 3a in 220% and
80% yield, respectively (yields are calculated on the basis of
Pd(OAc)2) (Scheme 3).8 Pure 2a could be purified carefully
by column chromatography. The geometry of the two double
bonds in 2a was established by the coupling constants in
1H NMR between related vinylic protons. Thus, J (H6-H7)
of 14 Hz and J (H4-H5) of 11 Hz manifest the (6E) and (4Z)
double bonds, respectively. Further evidence from NOESY
studies of the chloro derivative 2b unambiguously shows the
(E,Z)-configuration of the molecule.9
The formation of 2a and 3a could be explained by Scheme
4, which also rationalizes the stereoselectivity. First, trans-
halopalladation of acetylene gives the (E)-vinylpalladium
intermediate 4, which is inserted by a second molecule of
acetylene to form (E,Z)-dienylpalladium 5; after the insertion
of acrolein, the (2-oxoalkyl)palladium intermediate under-
goes protonolysis (path a) or â-hydride elimination (path b)
to afford 2a or 3a , respectively.
Our previous studies reveal that excess coordinating
halide inhibits â-H elimination and facilitates protonolysis
in acidic conditions.7 A number of reaction conditions were
screened. The results were summarized in Table 1.
Preliminary results showed that polar solvents, high
acetylene and halide concentration, and low temperature
favor the yield of 2a . In most cases, using HOAc as a solvent
and passing acetylene rapidly into the reaction mixture, 2a
was isolated as the main product after chromatography
(entries 3-5, Table 1). A codimerization byproduct of
acetylene and acrolein,10 which could be removed after
purification, could be detected in some cases by 1H NMR
spectra.
Acrolein was first selected to react with acetylene under
the catalysis of Pd(OAc)2. We first used acrolein as solvent
(1) (a) Lalonde, R. T.; Wong, C. F.; Hofstead, S. J .; Morris, C. D.; Gardner,
L. C. J . Chem. Ecol. 1980, 6, 35. (b) Baker, R.; Bradshaw, J . W. S. In
Aliphatic and Related Natural Product Chemistry; Gunstone, F. D., Ed.;
Specialist Periodical Report; Royal Society of Chemistry: London, 1983;
Vol. 3.
(2) Goldbach, M.; J a¨kel, E.; Schneider, M. P. J . Chem. Soc., Chem.
Commun. 1987, 1434.
(3) (a) Bergmann E. D. In Pesticide Chemistry, Vol. 1, Insecticides; Tahori,
A. S., Ed.; Gordon and Breach: New York, 1972; p 1. (b) Rossi, R.; Carpita,
A.; Quirici, M. G.; Gaudenzi, M. L. Tetrahedron 1982, 35, 631. (c) Stille, J .
K.; Simpson, J . H. J . Am. Chem. Soc. 1987, 109, 2138.
(4) Crombie, L.; Fisher, D. Tetrahedron Lett. 1985, 26, 2481.
(5) Alami, M.; Gueugnot, S.; Domingues, E.; Linstrumelle, G. Tetrahedron
1995, 51, 1209.
(6) Kaneda, K.; Uchiyama, T.; Fujuwara, Y.; Imanaka, T.; Taranash, S.
J . Org. Chem. 1979, 44, 55.
(7) (a) Wang, Z.; Lu, X. Chem. Commun. 1996, 535. (b) Wang, Z.; Lu, X.
J . Org. Chem. 1996, 61, 2254.
(8) The ratio of 2a to 3a was determined by the
1H NMR spectra of the
product mixture. The presence of the trienal product 3a was further
supported by GC-MS analysis and UV spectra.
We found that the LiBr-Pd(OAc)2 ratio has a great impact
on the reaction: when the LiBr-Pd(OAc)2 ratio was in-
(9) There is a strong NOE effect between H6 and H3 and no cross-peak
between H5 and H3.
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