A novel Lewis acid-promoted enyne cycloisomerization of triester-substituted alkenes

Article abstract of DOI:10.1039/b008103p

A novel cycloisomerization reaction of enynes 4 in the presence of ZnBr₂ and THF (1 eq.) in CH₂Cl₂ at -40 °C gave exo-methylenic 1,3-dienes 5 in moderate to good yield.

Full text of DOI:10.1039/b008103p

A novel Lewis acid-promoted enyne cycloisomerization of triester-substituted
alkenes†
Shoko Yamazaki,*a Kuriko Yamada,a Tetsuya Otsubo,a Masayo Haruna,a Emiko Kutsuwaa and
Hatsue Tamurab
a Department of Chemistry, Nara University of Education, Takabatake-cho, Nara 630-8528, Japan.
E-mail: yamazaks@nara-edu.ac.jp
b Department of Applied Chemistry, Graduate School of Engineering, Osaka University, 1-16 Machikaneyama,
Toyonaka, Osaka 560-0043, Japan
Received (in Cambridge, UK) 6th October 2000, Accepted 31st October 2000
First published as an Advance Article on the web 15th December 2000
A novel cycloisomerization reaction of enynes 4 in the
presence of ZnBr2 and THF (1 eq.) in CH2Cl2 at 240 °C gave
exo-methylenic 1,3-dienes 5 in moderate to good yield.
13C-HSQC, HMBC and NOESY spectra were in agreement
with the lactone structure drawn in eqn. (2). The crystal
structure of 5a was elucidated by X-ray diffraction analysis
(Fig. 1).** The diene is slightly twisted from the plane in order
to reduce steric repulsion between the ester and HPhCN groups;
the torsion angle of the diene moiety (•C5-C3-C2-C12) is
21.9°. This cisoid diene may be effective as an acceptor in the
inverse electron demand Diels–Alder reaction (see below).
Lewis acid-promoted reactions are an important part of modern
synthetic chemistry.1 Recently, prototropic cycloisomerization
reactions of enynes and dienes have been recognized as atom-
economic tools to construct rings, and transition metal-
catalyzed cycloisomerizations in particular have received much
attention.2 However, only a few examples of Lewis acid-
promoted cycloisomerizations (intramolecular ene reactions)
have been reported so far.3,4a,b
(2)
The design of a Lewis acid-promoted enyne cyclization
requires that a highly electrophilic alkene (or alkyne) has
coordination sites for a Lewis acid and that the other component
(alkyne or alkene) works as a nucleophile. Alkenes with three
ester groups are considered to be highly electrophilic and very
reactive towards nucleophilic olefins,5 and they may react
intramolecularly with alkynes which are relatively unreactive
nucleophiles.6‡ We thus examined Lewis acid-promoted intra-
molecular cyclization of the designed triester-substituted alkene
1. Reaction of 1 in the presence of ZnBr2 at rt gave cyclized
product 2 and H2O-adduct 3 in 45% and 10% yields,
respectively (eqn. (1)).
(1)
The formation of 2 can be explained as shown in Scheme 1.§
Nucleophilic attack of the alkyne moiety to the electrophilic
olefin complexed with ZnBr2 in A gives intermediate B.¶ A
1,3-hydride shift then leads to complex C, which isomerizes and
then forms diene 2 with Et3N. The formation of hydrated
product 3 is presumed to result from attack by trace amounts of
water on complex A.
If the isomerization step in C is prevented, exo-methylenic
1,3-dienes should be the primary products in this process. The
enyne 4, which is prevented from undergoing isomerization due
to the lack of a proton, was designed and Lewis acid mediated
reactions examined. After several conditions were examined
(see below), reaction of 4 in the presence of ZnBr2 (1.2 eq.) and
THF (1 eq.) in CH2Cl2 at 240 °C for 17–19 h gave exo-
methylenic 1,3-dienes 5 in 29–67% yields (eqn. (2), Table 1).∑
The g-lactone structure of 5 was suggested by the presence of a
characteristic CNO absorption (1771–1779 cm21). 1H, 13C, 1H/
Scheme 1
Table 1 Cycloisomerization of 4 to 5
Substratea R1
R2
Ar
Product (yield)
4a
4b
4c
4d
4e
H
H
H
Me
Et
Et
Et
Et
Et
Ph
p-Tol
5a (67%)
5b (58%)
p-MeO-C6H4 5c (41%)
Ph
Ph
5d (53%)
5e (46%)
(4e recovered 36%)
5f (29%)
5g (50%)b
n-Propyl
4f
4g
H
H
Me
iPr
Ph
Ph
a All reactions were carried out using 0.30–0.58 mmol of 4, 1.2 eq. of
ZnBr2, and 1.0 eq. of THF at 0.41 M for 4 in CH2Cl2 at 240 °C for 17–19
h, unless otherwise noted. b THF was not added. Addition of THF gave 5g
in 40% yield along with recovered 4g (24%).
† Electronic supplementary information (ESI) available: experimental
procedures and spectral data for described compounds and crystallographic
data for 5a. See http://www.rsc.org/suppdata/cc/b0/b008103p/
DOI: 10.1039/b008103p
Chem. Commun., 2001, 69–70
This journal is © The Royal Society of Chemistry 2001
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reaction provides a highly efficient means to prepare electron-
deficient cyclic dienes. The application of this methodology
towards the construction of carbocycles and diverse hetero-
cycles is under investigation.
We are grateful to Dr K. Yamamoto (Osaka University) for
measurement of mass spectra and elemental analysis. We thank
Mr Y. Yanase for experimental assistance.
Fig. 1 ORTEP drawing of 5a (50% probability ellipsoids). Selected bond
lengths (Å) and torsion angle (°): C1–C2 = 1.499(3); C2–C3 = 1.460(2);
C3–C4 = 1.501(2); C1–O1 = 1.344(2); O1–C4 = 1.444(2); C2–C12 =
1.345(2); C3–C5 = 1.344(2); •C5–C3-C2–C12 = 21.9(3). More detailed
structure data are given in the supplementary data.
With 4a,b, the yield of 5 decreased when THF was omitted
from the reaction (for 5a to 11–36%, for 5b to 11–25%).†† The
effect of THF is presumed to be that coordination of THF to Zn
adjusts the strength of the Lewis acid and prevents side
reactions.‡‡ For 4g, the reaction without THF gave a slightly
better yield (see Table 1).
Use of ZnI2–THF instead of ZnBr2–THF gave 5a in 62%
yield. Use of SnCl4 (278 °C) or ZnCl2–THF (240 °C) gave 5a
in lower yield (24–-39% including inseparable complex
mixtures). The reaction of 4a with ZnBr2–THF was also
performed at a higher temperature (0 °C to rt), however, the
yield of 5a decreased (32%), probably because of the instability
of the diene product. The reaction of 4a using 0.3 eq. of ZnBr2–
THF afforded 19% of 5a along with recovered 4a (62%),
therefore the reaction requires a stoichiometric amount of Lewis
acid.§§
Notes and references
‡ Thermal ene reactions6a,b and FeCl3-promoted chlorinated cyclizations6c
of allylic and propargylic esters of ethylenetricarboxylic acid have been
reported.
§ The alternative mechanism is that 1 undergoes an ene reaction initially to
give a cyclic allene that rearranges to 2.
¶ The coordination of a Lewis acid to a C·C bond was reported recently.12
The intermediate A (Scheme 1) can be drawn as shown above.
∑ Cyclizations were also examined using 10a–c as substrates. Using similar
conditions, only starting material was recovered.
** Crystal data: C18H18O6, M = 330.34, monoclinic, a = 8.1206(3), b =
10.5914(3), c = 19.7984(7) Å, b = 100.513(1)°, V = 1674.2(1) Å3, T =
296 K, space group P21/c (no. 14), Z = 4, m(Mo-Ka) = 0.099 mm–1
,
number of reflections measured = 4062, number of independent reflections
= 3845 (Rint = 0.025), R, Rw = 0.047, 0.052 for 2473 observed reflections
(I
> 2s(I)). CCDC 182/1839. See http://www.rsc.org/suppdata/cc/b0/
Thermal reactions of 4a and 1 (CH3CN, 80 °C, 24 h or
toluene, 110 °C, 24 h) without Lewis acid only afforded
complex mixtures along with recovered starting materials
(38–87%). A RuClH(CO)(PPh3)3-catalyzed reaction (toluene,
110 °C, 7 h) of 4a was examined but did not proceed.8
Only a few examples of synthesis of heterocycles by
cycloisomerization using transition metal catalysts have been
reported.9 Therefore, the present method should provide an
efficient alternative to transition metal-catalyzed cycloisomer-
izations. Also, the product cyclic dienes are electron-deficient
and suitable for cycloadditions such as inverse electron demand
Diels–Alder reaction10 and transition metal-catalyzed [4 + 3]
cycloadditions.11 The inverse electron demand Diels–Alder
reactions of 5a with the electron rich dienophiles 6 and 8 were
thus examined (eqn. (3)). C–C bond formation proceeds readily,
however, the observed regio- and stereoselectivity was low.¶¶
b008103p/ for crystallographic files in .cif format.
†† The reaction of 4a in THF as a solvent did not proceed.
‡‡ Use of propylene oxide instead of THF in the reaction of 4a gave 5a in
lower yield (28%), along with recovered 4a (21%). The combination of
Lewis acid and Lewis base is used in some Lewis acid-mediated
reactions.7
§§ Formation of cyclic dienes is in marked contrast with the FeCl3-
promoted reaction of dimethyl ester analog of 1 and 4d giving chlorinated
cyclization products.6c Investigation of the difference in Lewis acids is
underway.
¶¶ The stereochemistries of 7a, 7b and 7bA were tentatively assigned as
shown in the supplementary information by the observed NOE’s.
1 Selectivities in Lewis Acid Promoted Reactions, ed. D. Schinzer, Kluwer
Academic Publishers, Dordrecht, 1989; S. Shambayati and S. L.
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Kitamura, Y. Okada and J. Ichikawa, J. Org. Chem., 1994, 59, 6717.
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5424.
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Roush and T. A. Killinger, J. Am. Chem. Soc., 1979, 101, 6023; (c) B. B.
Snider and D. M. Roush, J. Org. Chem., 1979, 44, 4229.
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8 M. Nishida, N. Adachi, K. Onozuka, H. Matsumura and M. Mori,
J. Org. Chem., 1998, 63, 9158.
(3)
9 B. M. Trost, E. D. Edstrom and M. B. Carter-Petillo, J. Org. Chem.,
1989, 54, 4489.
10 G. J. Bodwell and Z. Pi, Tetrahedron Lett., 1997, 38, 309; H. L.
Gingrich, D. M. Roush and W. A. Van Saun, J. Org. Chem., 1983, 48,
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12 N. Asao, T. Asano, T. Ohishi and Y. Yamamoto, J. Am. Chem. Soc.,
2000, 122, 4817.
In summary, a novel Lewis acid-promoted enyne cycloiso-
merization to give cyclic dienes has been developed. This new
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Chem. Commun., 2001, 69–70