A simple route to selective Diels-Alder reactions using modified zeolite Y

Article abstract of DOI:10.1246/cl.2000.358

Synthetically useful Diels-Alder reactions of different dienophiles with cyclopentadiene in the presence of chirally modified zeolite Y as simple and accessible medium led to high rate and diastereoselectivity and low to moderate enantioselectivity.

Full text of DOI:10.1246/cl.2000.358

358
Chemistry Letters 2000
A Simple Route to Selective Diels-Alder Reactions Using Modified Zeolite Y
H. Mahmoudi Najafi, M. Ghandi,* and F. Farzaneh†
Department of Chemistry, Faculty of Science, University of Tehran, P.O. Box 14155-6455, Tehran, Iran
† Department of Chemistry, University of Az-Zahra, Tehran, Iran
(Received November 9, 1999; CL-990958)
Synthetically useful Diels-Alder reactions of different
cedure, 1 mmol of the dienophile (methyl vinyl ketone and
methyl acrylate) and 1.2 mmol of freshly distilled cyclopentadi-
ene were added to 20 ml of CH2Cl2 containing 1 g of vacuum
pre-dried zeolite catalyst. The mixture was stirred for 4 h under
dienophiles with cyclopentadiene in the presence of chirally mod-
ified zeolite Y as simple and accessible medium led to high rate
and diastereoselectivity and low to moderate enantioselectivity.
o
nitrogen atmosphere at 0 C. After filtration the filtrate was
concentrated under reduced pressure by a rotary evaporator. We
used the NMR method to analyze the products in the presence
of chiral shift reagent Eu(hfpc)3.14 The results are shown in
Table 1. The reaction in the presence of zeolite loaded with (-)-
ephedrine and (-)-diethyl tartrate could not be conducted since
the chiral compound will immediately diffuse out of the cavi-
ties in moderate to high polar solvents (CH2Cl2).
In the absence of catalyst, the Diels-Alder reactions some-
times require high temperature and/or high pressure. It was
therefore a major breakthrough when it was found that Lewis
acids (e.g. AlCl3) catalyze the Diels-Alder reactions allowing
running in very mild conditions often below 0 °C to afford high
rate and stereoselectivity. In order to enhance the rate and
selectivity, the reaction has been performed using a variety of
catalysts or under specific reaction conditions: 1) by using
homogeneous Lewis acids1 or heterogeneous acids,2 2) under
high pressure,3 3) in aqueous media,4 4) in confined spaces.5
The asymmetric Diels-Alder reaction was first investigated
by introducing a chiral auxiliary on the dienophile and then suc-
cessfully followed by using chiral Lewis acids,6 as the efficient
work of Corey which afforded the ee of 96:4 in the reaction of 2-
bromoacrolein with furan.7 Although, recent work of Itsuno,8
which has used new chiral polymeric catalyst, and the results of
moderate to high ee is remarkable, the method cannot be recom-
mended to organic synthetic chemists due to the complexity of
the catalyst.
We also used the loading method in order to compare the
results of reactions taking place inside the cavities with those
obtained in the aforementioned synthetic procedure (see Table
1).15 Under the synthetic conditions, the diene and dienophile
have a lower chance to condense and form the cycloadduct out-
side the supercages due to lack of the required activation energy
o
available at 0 C. The reaction takes place as soon as the sub-
Combined characters of acidic sites (Lewis and Brønsted)
and shape medium which both enhance the rate and diastereose-
lectivity of Diels-Alder cycloadducts are remarkably present in
the simple system of crystalline microporous solid which is
called zeolite. The reports on the observation of catalysis by zeo-
lite electron acceptors have prompted several investigators to use
the zeolites as catalysts in Diels-Alder reactions.9 It has been
observed that zeolites can dramatically enhance the rate, which is
comparable with the use of elevated pressure.10 Moreover, using
these catalysts have afforded highly regioselective and diastereo-
selective reactions and good to excellent yields.11 Our main goal
of this research was to design a very simple and easily accessible
system, which can promote the asymmetric Diels-Alder reaction.
Since, a part of our recent research group has been concentrated
on zeolite chemistry and its applications,12 and due to a recent
communication which has described using of zeolite Y included
chiral inductor successfully as a remarkable medium for the
intramolecular photocyclization reaction,13 we decided to study
the Diels-Alder reactions using chirally modified zeolite Y. Our
literature survey showed that these chirality inducing systems
have not been used before in Diels-Alder reactions.
strates collide with each other within the supercages, where the
rate enhances due to the presence of Lewis and Brønsted acidic
sites. The product will then be expelled outside with the aim of
solvent molecules and makes the microreactor host available
for reception of the reactant guest molecules. The lower enan-
tioselectivity observed in the synthetic method might be result-
ed either from the change in the reactivity of chirally modified
sites in different solvents or from that part of reactions taking
place outside the supercages. In both methods the best results
obtained with (-)-histidine·HCl as chiral inductor in NaY.
From the results presented in Table 1, we tentatively con-
clude that a three-point interaction between the dienophile mol-
ecule, the chiral inductor and the zeolite interior is necessary to
induce the chirality in the cycloadducts. The fact that low func-
tional chiral inductors fail to yield significant enantioselectivity
supports this idea (compare ephedrine with histidine). The
recognition points in the case of (-)-histidine·HCl are most
likely the carboxyl, amino and the imidazole groups of the chi-
ral inductor, the cations of the zeolite and the carbonyl group of
the dienophile. The cations present in the zeolite help to anchor
the chiral inductor to the interior surface. This arrangement is
expected to favor one of the modes of cycloaddition.
The catalysts were prepared by exchanging (-)-ephedrine
hydrochloride and (-)-histidine hydrochloride within NaY zeolite.
The loading (or exchanging) level of the chiral inductor was
maintained such that every supercage on an average contained
one molecule of the chiral compound. In a typical synthetic pro-
Due to rapid polymerization of such dienophiles and
cyclopentadiene, the yield decreases with longer reaction times
in homogeneous Diels-Alder reactions with or without
catalyst.16 In all of our reactions no trace of dicyclopentadiene
Copyright © 2000 The Chemical Society of Japan

Chemistry Letters 2000
359
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products even after preparative GC separation.17
3
4
5
G. Isaacs, Chem. Ber., 1987 , 47.
In another part of our research, we used alkali metal
exchanged zeolites Y to see the cation size effect on the dia-
stereoselectivity of the Diels-Alder reactions. For this, five dif-
ferent dienophiles have been used which consist of different
functional groups of ketone, ester and nitrile. These dienophiles
were reacted with cyclopentadiene in the presence of zeolites Y
exchanged with alkali metals (Li, Na, K, and Cs) in CH2Cl2 at 0
°C. The results are presented in Table 2.
We observed that by increasing the cation size (ionic radii)
the endo:exo ratio increases. This trend supports the shape
selectivity behavior of zeolite Y resulted in the formation of the
more compact endo adduct which has less molecular volume. It
is evident that even the smallest cation of the group (Li+)
exchanged within zeolite has a dramatic change on the
endo:exo ratio of cycloadducts of MA, MVK and MPK with
cyclopentadiene (see Table 2). CsY shows good to excellent
ratios with the maximum amount of about 99% in the case of
MA. Moreover, the improvement of synthetic yield percentage
compared to the standard procedure is consistent with the acidic
behavior of zeolite Y used in these reactions. Applying the
loading method in these reactions in n-hexane showed slight
diastereoselectivity improvement with respect to the synthetic
method. Therefore, the more diastereoselectivity is the conse-
quence of maximum shape selectivity since the reaction is tak-
ing place totally inside the cavities.
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14 Due to the presence of methyl groups in MA and MVK and their sim-
ple characterization in NMR spectra we used the NMR method to
obtain the endo:exo ratio and the ee of the products using chiral shift
reagent.
15 Loading procedure: The zeolites were exchanged by the chiral com-
pound according to the reported procedure (reference 13). The vacu-
um dried zeolite was added to the dienophile (1 mmol) solution in n-
hexane (zeolite:dienophile weight ratio = 25:1) and the mixture was
stirred at room temperature for 3 h. After filtration and washing with
n-hexane, GC or UV analysis of the hexane layer revealed that no
dienophile was left. To the magnetically stirred slurry of dienophile-
zeolite complex in n-hexane a solution of cyclopentadiene in n-hexane
was added at once (2:1 molar ratio of diene:dienophile) and the mix-
ture stirred for 4 h at room temperature. After filtration and washing
with more n-hexane and small portions of diethyl ether, GC analysis
of the filtrate revealed no product in the filtrate. The product was
readily extracted into the ether layer by stirring the zeolite in diethyl
ether overnight (mass balance ~ 90%). The product was analyzed by
GC (using 10 ft. OV-17 on Chromosorb column with cyclohexanone
as internal standard) and NMR for endo:exo ratio and ee using a chiral
shift reagent. The absolute configuration has not been determined.
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(1976).
In summary we have shown that high rate, diastereoselec-
tivity and low to moderate enantioselectivity have been
obtained using modified zeolite Y as microreactor.
Acknowledgment is made to the Research Council of the
University of Tehran for support of this research.
References and Notes
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2