A novel method for the construction of (Z,E)- or (Z,Z)-conjugated alkadienyl carboxylates

Article abstract of DOI:10.1021/ol026286p

(Matrix presented) The stereocontrolled dehydrobromination of 1,2-dibromoethyl carboxylates giving (Z)-2-bromovinyl carboxylates could readily be approached by using DBU and a catalytic amount of hydroquinone as a base at -78°C. The first investigation on

Full text of DOI:10.1021/ol026286p

ORGANIC
LETTERS
2002
Vol. 4, No. 16
2759-2762
A Novel Method for the Construction of
(Z,E)- or (Z,Z)-Conjugated Alkadienyl
Carboxylates
Rong He and Min-Zhi Deng*
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic
Chemistry, Academy of Sciences, 354 Fenglin Lu, Shanghai 200032, P.R. China
dengmz@pub.sioc.ac.cn
Received June 3, 2002
ABSTRACT
The stereocontrolled dehydrobromination of 1,2-dibromoethyl carboxylates giving (Z)-2-bromovinyl carboxylates could readily be approached
by using DBU and a catalytic amount of hydroquinone as a base at −78 °C. The first investigation on the Suzuki-type cross-coupling of
(Z)-2-bromovinyl carboxylates as electrophiles with stereodefined alkenylboronic acids provides a novel method for the construction of (Z,E)-
or (Z,Z)-conjugated alkadienyl carboxylate moieties, which are often present in a range of natural products.
Conjugated alkadienyl carboxylate moieties not only are
found in a growing class of natural products isolated from a
wide spectrum of marine organisms with important physi-
ological properties1 but also are recognized to be important
precursors to prepare a wide range of natural products by
Diels-Alder reaction.2 Among the methods for the prepara-
tion of conjugated alkadienyl carboxylates, the traditional
enolacetylation of trans-2-alkenylal with acetic anhydride
in the presence of base led to a mixture of all four isomers
of alkadienyl acetate.3a It was found that stereodefined (E,E)-
or (E,Z)-conjugated alkadienyl carboxylates could be pre-
pared in a few steps from pyridine1d and (E,Z)-alkadienyl
carboxylates also could be obtained by the stereocontrolled
hydrogenation of (E)-alkynylvinyl carboxylates.1c Bruneau
reported that ruthenium-catalyzed addition of carboxylates
to terminal alkynes can afford (Z)-alk-1-en-yl esters including
conjugated dienyl esters.3b However, to the best of our
knowledge, the general method for the stereodefined prepa-
ration of (Z,E)- or (Z,Z)-conjugated alkadienyl carboxylates
has not been reported, perhaps becuase of its thermodynamic
instability.1d,4 So, it seems important to develop an effective
method for the construction of (Z,E)- or (Z,Z)-conjugated
alkadienyl carboxylates. In this communication, we wish to
report a novel approach to (Z,E)- or (Z,Z)-conjugated
alkadienyl carboxylates.
* To whom correspondence should be addressed. Fax: 86-21-64166128.
(1) (a) Gerwick, W. H.; Sitachitta, N. J. Nat. Prod. 1998, 61, 681-684.
(b) Fu¨rstenberger, G.; Hecker, E. Tetrahedron Lett. 1977, 925-928. (c)
Corey, E. J.; Wright, S. W. J. Org. Chem. 1990, 55, 1670-1673. (d) Becher,
J. Synthesis 1980, 589-612. (e) Leete, E.; Mueller, M. E. J. Am. Chem.
Soc. 1982, 104, 6440-6444.
(2) (a) Barrett, A. G. M.; Barta, T. E.; Flygare, J. A.; Sabat, M.; Spilling,
C. D. J. Org. Chem. 1990, 55, 2409-2414. (b) Shibata, J.; Shiina, I.;
Mukaiyama, T. Chem. Lett. 1999, 313-314. (c) Hirsenkorn, R.; Haag-zeino,
B.; Schmidt, R. R. Tetrahedron Lett. 1990, 31, 4433-4436.
(3) (a) Cecchi, R.; Favara, D.; Omodei-sale´, A.; Depaoli, A.; Consonni,
P. Gazz. Chim. Ital. 1984, 114, 225-231. (b) Doucet, H.; Derrien, N.;
Kabouche, Z.; Bruneau, C.; Dixneuf, P. H. J. Organomet. Chem. 1997,
551, 151-157.
As is well-known, the transition metal catalyzed Suzuki
cross-coupling reaction is one of the most efficient methods
for the construction of carbon-carbon bonds, especially for
the formation of general dienes.5 Apparently, it is a reason-
able route to synthesis of (Z,E)- or (Z,Z)-conjugated alka-
(4) (a) So¨derberg, B. C.; O’Neil, S. N.; Chisnell, A. C.; Liu, J.
Tetrahedron 2000, 56, 5037-5044. (b) So¨derberg, B. C.; Liu, J.; Ball, T.
W.; Turbeville, M. J. J. Org. Chem. 1997, 62, 5945-5952.
10.1021/ol026286p CCC: $22.00 © 2002 American Chemical Society
Published on Web 07/16/2002

dienyl carboxylates by the Suzuki-type coupling reaction of
(Z)-2-bromovinyl carboxylates as electrophiles with alkenyl-
boron reagents. Accordingly, the successful preparation of
(Z)-2-bromovinyl carboxylates and the selection of coupling
conditions are the key to realize the route. Although many
reports regarding cross-coupling reactions6 of general alkenyl
halides, including enol acetates of 2-bromo ketones,6c with
aryl and alkenylboron reagents exist, the cross-coupling of
(Z)-2-bromovinyl carboxylate as a special electrophile has
not appeared in the literature, perhaps owing to its difficult
availability. We improved the synthesis process of (Z)-2-
bromovinyl carboxylate and first investigated its Suzuki-type
cross-coupling reaction. Herein, we wish to report the
experiment results.
It was reported that (Z)-2-bromovinyl acetate could be
obtained with 6.8% yield by the dehydrobromination of 1,2-
dibromoethyl acetate using N,N-diethylaniline as a base.7
Widlanski et al. described only one example of the synthesis
of (Z)-2-bromovinyl benzoate with moderate yield.8 The
interest in (Z)-2-bromovinyl carboxylates as coupling precur-
sors led us to improve the dehydrobromination of 1,2-
dibromoethyl carboxylates. Fortunately, we found that DBU
with a catalytic amount of hydroquinone at -78 °C could
stereospecifically dehydrobrominate 1,2-dibromoethyl car-
boxylates to afford (Z)-2-bromovinyl carboxylates in moder-
ate yields (Scheme 1).
Table 1. Effect of Bases and Solvents on the Coupling
Reaction of trans-Heptenylboronic Acid with (Z)-2-bromovinyl
Octanoatea
entry
conditions
yield (%)b
1
2
3
4
5
6
7
8
9
10
11
12
13
dioxane, K3PO4‚3H2O, PdCl2dppf
dioxane, Tl2CO3, Pd(PPh3)4
nr
32
14
33
47
3
43
18
32
40
64
84
86
dioxane, NBu4I, K3PO4‚3H2O, Pd(PPh3)4
toluene, K3PO4‚3H2O, Pd(PPh3)4
dioxane, Ag2O/Cs2CO3, Pd(PPh3)4
dioxane, Cu2O/K2CO3, Pd(PPh3)4
dioxane, K2CO3, PdCl2(MeCN)2, PPh3
dioxane, K3PO4‚3H2O, PdCl2(PPh)3
THF, K2CO3, Pd(PPh3)4
dioxane, Ag2O/K2CO3, Pd(PPh3)4
dioxane, K3PO4‚3H2O, Pd(PPh3)4
dioxane, KF‚2H2O, Pd(PPh3)4
dioxane, K2CO3, Pd(PPh3)4
a All reactions were carried out using a mixture of trans-heptenylboronic
acid (1.2 mmol), (Z)-2-bromovinyl octanoate (1 mmol), 3% catalyst, and
base (3 equiv) in 4 mL of solvent, for 10 h, at 90 °C (except for entry 9,
the reaction was carried out under reflux). b Yields of isolated product based
on the amount of (Z)-2-bromovinyl octanoate used.
coupling reaction of alkylboronic esters with alkenyl or aryl
halides.10 The combinations of Ag2O and Cu2O with some
bases could also dramatically enhance the rates of the
coupling of some substrates.11 Unfortunately, in this case,
the special bases mentioned above did not make the coupling
yields increase (entries 2, 5, 6, and 10). Further studies
showed that KF‚2H2O and K2CO3 effectively promoted the
cross-coupling reaction (entries 12 and 13). The satisfactory
coupling yields of 84%and 86% could be achieved by
carrying out the reaction in dioxane at 90 °C using Pd(PPh3)4
as the catalyst and KF‚2H2O or K2CO3 as a base.
Scheme 1
With the (Z)-2-bromovinyl carboxylates in hand, we
optimized the coupling reaction conditions using trans-
heptenylboronic acid and (Z)-2-bromovinyl octanoate as
reactants. The results are shown in Table 1 and demonstrate
that Pd(0) catalyst was superior to Pd(II) catalyst for the
reaction (entry 11 vs 1, 8 and 13 vs 7) and dioxane appeared
to be a better solvent than THF or toluene (entry 13 vs 9
and 11 vs 4). It was reported that the use of phase transfer
catalysts benefited the occurrence of some coupling reac-
tions,9 but the addition of phase transfer catalyst NBu4I failed
to improve the yield in the reaction (entry 3). Suzuki et al.
reported that thallium(I) salts effectively promoted the
The reactions of various alkenylboronic acids with (Z)-
2-bromovinyl carboxylates were explored under optimized
conditions. The results are collected in Table 2.
As shown in Table 2, the cross-coupling reaction of trans-
or cis-alkenyl boronic acids with various (Z)-2-bromo-vinyl
carboxylates proceeded readily to give the corresponding
(Z,E)- or (Z,Z)-conjugated alkadienyl carboxylates in satis-
1
1
factory yields. The H NMR and H-1H COSY spectra of
the coupling products confirmed that the configurations of
both double bonds of the products were the same as that of
the starting materials. When phenylboronic acid as a coupling
partner was coupled with (Z)-2-bromovinyl octanoate, it was
found that the reaction afforded a part of (E)-phenylvinyl
carboxylate except the major (Z)-phenylvinyl carboxylate
(5) (a) Cassani, G.; Massardo, P.; Piccardi, P. Tetrahedron Lett. 1983,
24, 2513-2516. (b) Roush, W. R.; Warmus, J. S.; Works, A. B. Tetrahedron
Lett. 1993, 4427-4430. (c) Miyaura, N.; Suginome, H. Tetrahedron 1983,
39, 3271-3277.
(6) (a) Miyaura, N.; Suzuki, A. Chem. ReV. 1995, 95, 2457-2483. (b)
Suzuki, A. J. Organomet. Chem. 1999, 576, 147-168. (c) Abe, S.; Miyaura,
N.; Suzuki, A. Bull. Chem. Soc. Jpn. 1992, 65, 2863-2865.
(7) Izumi, M.; Aiko, I.; Yokoo, M.; Kimoto, H. J. Pharm. Soc. Jpn.
1952, 72, 21-26.
(8) Stowell, J. K.; Widlanski, T. S. J. Am. Chem. Soc. 1994, 116, 789-
790.
(9) Chow, H. F.; Wan, C. W.; Low, K. H.; Yeung, Y. Y. J. Org. Chem.
2001, 66, 1910-1913.
(10) Sato, M.; Miyaura, N.; Suzuki, A. Chem. Lett. 1989, 1405-1408.
(11) (a) Uenishi, J.; Beau, J. M.; Armstrong, R. W.; Kishi, Y. J. Am.
Chem. Soc. 1987, 109, 4756-4758. (b) Hirabayashi, K.; Kawashima, J.;
Nishihara, Y.; Mori, A.; Hiyama, T. Org. Lett. 1999, 1, 299-301. (c) Chen,
H.; Deng, M.-Z. Org. Lett. 2000, 2, 1649-1651. (d) Liu, X.-X.; Deng,
M.-Z. Chem. Commun. 2002, 622-623.
2760
Org. Lett., Vol. 4, No. 16, 2002

Table 2. Palladium-Catalyzed Cross-Coupling Reactions of Organoboronic Acids with Various (Z)-2-Bromovinyl Carboxylatesa
a All reactions were carried out using a mixture of alkenylboronic acids (1.2 mmol) and (Z)-2-bromovinyl carboxylates (1 mmol), 3 equiv of K2CO3, and
3% Pd(PPh3)4 in 4 mL of dioxane at 90 °C under a nitrogen atmosphere for 10 h. All products were identified by 1H NMR, 13C NMR, IR, and mass spectra
1
and HRMS. b When the reaction was carried out at 90 and 60 °C, H NMR spectra showed that the corresponding Z/E ratios of the coupling product were
83:17 and 96:4, respectively.
(entry 10). The 1H NMR spectra of the products showed the
Z/E ratio to be 83:17, when the reaction was carried out at
90 °C. When the reaction took place at 60 °C, the Z/E ratio
was 96:4. It seems that lower reaction temperature benefits
the formation and the configuration retention of (Z)-form
product.
Org. Lett., Vol. 4, No. 16, 2002
2761

In summary, the dehydrobromination conditions of 1,2-
dibromoalkyl carboxylates were improved, and high stereo-
selective (Z)-2-bromoalkenyl carboxylates could be easily
obtained in moderate yield. The palladium-catalyzed cross-
coupling reaction of (Z)-2-bromoalkenyl carboxylates and
alkenylboronic acids to give (Z,E)- or (Z,Z)-conjugated
alkadienyl carboxylates has been first achieved. Thus, a novel
practical method for the stereocontrollable construction of
(Z,E)- or (Z,Z)-conjugated alkadienyl carboxylate moieties
is provided. The present method has opened the door to the
synthesis of some natural products having the interesting
structure moieties. Further study on the scope of the reaction
is currently underway in our laboratory.
Acknowledgment. We thank the NNSF of China and
State Key Laboratory of Organometallic Chemistry, Shanghai
Institute of Organic Chemistry, Chinese Academy of Sci-
ences, for financial support.
Supporting Information Available: Experimental details
and spectra. This material is available free of charge via the
Internet at http://pubs.acs.org.
OL026286P
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Org. Lett., Vol. 4, No. 16, 2002