Tandem Diels-Alder aromatization reactions of furans under unconventional reaction conditions - Experimental and theoretical studies

Article abstract of DOI:10.1002/1099-0690(200108)2001:15<2891::AID-EJOC2891>3.0.CO;2-M

Silica-supported Lewis acids are good catalysts for Diels-Alder reactions between furan and acrylonitrile and methyl acrylate at room temperature. When 2,5-dimethylfuran is used as the diene, yields of the Diels-Alder adducts with methyl acrylate are lower, due in part to the appearance of aromatization products. The use of microwave activation results in some cases in good yields of aromatic products and, as such, constitutes a good synthetic route to polysubstituted aromatic compounds. Computational studies on the reaction mechanism and the role of the catalyst on the product distribution show that "hard" Lewis acids, such as aluminum derivatives, make ring-opening of the adduct much easier, affording aromatic products. The theoretical results are in excellent agreement with the relative reactivity observed for the different dienes and dienophiles.

Full text of DOI:10.1002/1099-0690(200108)2001:15<2891::AID-EJOC2891>3.0.CO;2-M

FULL PAPER
Tandem Diels؊Alder Aromatization Reactions of Furans under Unconventional
Reaction Conditions ؊ Experimental and Theoretical Studies
[a]
[a]
[a]
[b]
´
´
´
´
´
Jose M. Fraile, Jose I. Garcıa, Marıa A. Gomez, Antonio de la Hoz,*
[a]
[b]
[b]
[a]
´
´
Jose A. Mayoral,* Andres Moreno, Pilar Prieto, Luis Salvatella, and
[b]
´
Ester Vazquez
Dedicated to Prof. Luis Oro[‡]
Keywords: Cycloadditions / Density functional calculations / Furans / Heterogeneous catalysis / Lewis acids / Microwaves
Silica-supported Lewis acids are good catalysts for
Diels−Alder reactions between furan and acrylonitrile and
methyl acrylate at room temperature. When 2,5-dimethylfu-
aromatic compounds. Computational studies on the reaction
mechanism and the role of the catalyst on the product distri-
bution show that ‘‘hard’’ Lewis acids, such as aluminum de-
ran is used as the diene, yields of the Diels−Alder adducts rivatives, make ring-opening of the adduct much easier, af-
with methyl acrylate are lower, due in part to the appearance fording aromatic products. The theoretical results are in ex-
of aromatization products. The use of microwave activation
cellent agreement with the relative reactivity observed for
results in some cases in good yields of aromatic products and, the different dienes and dienophiles.
as such, constitutes a good synthetic route to polysubstituted
Introduction
AlCl[12,13] supported on silica gel are suitable catalysts for
DielsϪAlder reactions between furan and a number of di-
enophiles,[14] including chiral acrylates,[15] under mild but
unconventional reaction conditions (use of a solid catalyst
in the absence of a solvent). In view of these results, we
considered it interesting to explore the use of silica-sup-
ported Lewis acids as catalysts in DielsϪAlder reactions of
2,5-dimethylfuran.
DielsϪAlder reactions of furan and its derivatives have
received a great deal of attention; this interest is for two
main reasons. Firstly, furan and some of its derivatives are
inexpensive compounds obtained from agricultural by-
products.[1] Secondly, the cycloadducts are versatile inter-
mediates in the preparation of carbohydrates and other bio-
logically active compounds.[2]
The use of furans as dienes has resulted in some problems
related to their sensitivity to the most common Lewis acid
catalysts, the ease of reversibility of their reactions, and the
formation of by-products. In view of these drawbacks, a
range of special reaction conditions has been developed in-
cluding, for instance, very long reaction times,[3] high pres-
sure,[4,5] ZnI2 in sealed tubes,[6] cupric fluoroborate and
long reaction times,[7] cation-exchanged K10 clays,[8] Y ze-
olite,[9] and, more recently, chiral bis(oxazoline)copper cata-
lysts.[10] We have shown that ZnCl2,[11] TiCl4, and Et2-
Results and Discussion
Experimental Reactivity Results
Firstly, we compared the behavior of furan (1) and 2,5-
dimethylfuran (2) in their reactions with methyl acrylate
(3a) and acrylonitrile (3b), catalyzed by silica and by three
silica-supported Lewis acids (Scheme 1 and Table 1). The
catalysts were obtained by treatment of silica with ZnCl2,
Et2AlCl, and TiCl4, and are henceforth denoted as Zn(Si),
Al(Si), and Ti(Si), respectively.
The results obtained depend on the nature both of the
diene and of the dienophile. As previously reported,[16]
Zn(Si) is a better catalyst than Al(Si) and Ti(Si) for
DielsϪAlder reactions involving α,β-unsaturated nitriles
such as acrylonitrile, and good yields of the corresponding
cycloadducts were obtained with this catalyst. With this di-
enophile, the reactions carried out using furan as the diene
produced the endo cycloadduct (4bn) as the major product,
the situation being reversed in the case of 2,5-dimethylfu-
ran, with which the exo cycloadduct (5bx) was the major
product. Any catalysis due to the support can be ruled out,
because the reaction is not promoted by silica gel (Table 1).
[a]
´
Instituto de Ciencia de Materiales de Aragon, Departamento
´
´
de Quımica Organica, Universidad de ZaragozaϪCSIC,
Facultad de Ciencias,
Pedro Cerbuna 12, 50009 Zaragoza, Spain
Fax: (internat.) ϩ 34-976/762077
E-mail: mayoral@posta.unizar.es
[b]
[‡]
´
´
´
´
Departamento de Quımica Inorganica, Organica y Bioquımica,
Facultad de Ciencias Quımicas, Universidad de Castilla-La
´
Mancha,
Campus Universitario, 13071 Ciudad Real, Spain
Fax: (internat.) ϩ 34-926/295318
E-mail: adlh@qino-cr.uclm.es
Aragon Award winner 2001
Supporting information for this article is available on the
WWW under http://www.wiley-vch.de/home/eurjoc or from
the author.
Eur. J. Org. Chem. 2001, 2891Ϫ2899
WILEY-VCH Verlag GmbH, 69451 Weinheim, 2001
1434Ϫ193X/01/0815Ϫ2891 $ 17.50ϩ.50/0
2891

A. de la Hoz, J. A. Mayoral et al.
FULL PAPER
Table 1. Results obtained on treatment of furan (1) and 2,5-dimethylfuran (2) with methyl acrylate (3a) and acrylonitrile (3b), carried
out at room temperature; n ϭ endo, x ϭ exo
Diene
Dienophile
Catalyst
t [h]
Yield of 4 or 5 (%)[a]
n/x[a]
Yield of 6 (%)[a]
1
3a
SiO2
24
24
24
3
24
24
24
24
2
24
3
3
3
3
75
75
71
78
Ϫ
24
25
32
8
Ϫ
Ϫ
79
Ϫ
15
86:14
81:19
73:27
67:33
Ϫ
66:34
63:37
75:25
62:38
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
6
Ϫ
14
Ϫ
Ϫ
Ϫ
Ϫ
Zn(Si)[b]
Ti(Si)[c]
Zn(Si)
Ti(Si)
1
2
3b
3a
SiO2
Zn(Si)
Al(Si)[c]
Ti(Si)
2
3b
SiO2
Ϫ
37:63
Ϫ
Zn(Si)
Al(Si)
Ti(Si)
38:62
[a]
[b]
[c]
Determined by NMR. Ϫ Ref.[11]. Ϫ Ref.[12,13]
The second competing reaction, not observed in the case
of acrylonitrile, is ring-opening of the cycloadducts, fol-
lowed by aromatization to yield methyl 2,5-dimethylbenzo-
ate (6a).
In order to modify the results, we decided to assess the
effect of temperature on the reactions. However, we found
that the use of conventional heating gave irreproducible re-
sults. It is known that mineral oxides are poor heat con-
ductors and that conventional methods result in inhomo-
geneous heating and even in overheating. Microwave irradi-
ation is an unconventional source of energy, the usefulness
of which in synthetic organic chemistry has been increas-
ingly recognized in recent years.[19,20] This energy source is
particularly suitable for reactions carried out with a solid
catalyst in the absence of a solvent.[21] In fact, metal oxides
do absorb microwaves efficiently and this phenomenon re-
sults in rapid and homogeneous heating of the reaction
mixture. In this manner, microwave activation in the pres-
ence of silica gel has enabled a furan derivative to undergo
successful intramolecular DielsϪAlder reaction even
though failing to undergo the reaction under normal ther-
mal treatment.[22] Microwave activation has also recently
been employed to carry out DielsϪAlder reactions of
furans promoted by K10[23] or without a catalyst.[24]
First of all, we used microwave activation in the treat-
ment of 2,5-dimethylfuran with methyl acrylate and acry-
lonitrile, using a focused microwave reactor, and the results
obtained in these experiments are collected in Table 2.
In agreement with previous studies, silica gel was not very
Scheme 1
In the reactions carried out with methyl acrylate as the
dienophile, the use of silica-supported Lewis acids resulted
in good yields of the corresponding cycloadducts 4an and
4ax when furan was used as the diene,[14,15] but the yields
obtained with this dienophile and 2,5-dimethylfuran were
much lower. These results do not indicate that 2,5-dimethyl-
furan is necessarily less reactive than furan, but more that
the difficulty in obtaining good yields was due to competi-
tion from other reactions.
The first of these reactions is the retro DielsϪAlder reac-
tion. The equilibrium position changes from one diene and efficient in the promotion of the reactions. With methyl ac-
one dienophile to another. Cook and Cracknell have de- rylate, an increase in the amount of aromatic product was
scribed[17] reactions of fumaronitrile in which there was a observed, probably accompanied by an increase in the retro
greater yield of cycloadducts with 2,5-dimethylfuran than DielsϪAlder reaction. In fact, a small amount of cycload-
with furan. On the other hand, Dewar and Pierini[18] have duct was only obtained when the Zn(Si) catalyst was used.
reported that this behavior was reversed when maleic an- In the reactions involving acrylonitrile, the corresponding
hydride (a dienophile more similar to methyl acrylate) is aromatic product was not obtained. Nevertheless, the reac-
used as a dienophile. Furthermore, both the forward and tion results were not noticeably improved and only with
reverse reactions are faster with 2,5-dimethylfuran, meaning Zn(Si) were cycloadducts achieved, in a yield of 80%, in
that equilibrium is also reached more quickly.
this case using a relatively low temperature and a reaction
2892
Eur. J. Org. Chem. 2001, 2891Ϫ2899

Tandem DielsϪAlder Aromatization Reactions of Furans
FULL PAPER
Table 2. Results obtained on treatment of 2,5-dimethylfuran (2) with methyl acrylate (3a) and with acrylonitrile (3b), carried out in a
focused microwave reactor under argon pressure; n ϭ endo, x ϭ exo
Dienophile
Catalyst
T [°C]
p [bar]
t [min]
Yield of 5 (%)[a]
5n/5x[a]
Yield of 6 (%)
3a
SiO2
SiO2
90
70
85
70
50
70
70
70
70
70
40
3
3
Ϫ
Ϫ
Ϫ
Ϫ
3
3
3
3
3
15
30
45
45
15
15
15
15
15
15
7
8
9
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
67:33
65:35
48:52
50:50
50:50
50:50
48:52
Ϫ
Ϫ
[b]
Ti(Si)
Al(Si)
Zn(Si)
Zn(Si)
SiO2
Ti(Si)
Al(Si)
Zn(Si)
Zn(Si)
[b]
Ϫ
10
29
24
11
15
65
80
Ϫ
[b]
3b
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
[a]
[b]
Determined by NMR. Ϫ The appearance of more than 20% of 6a was observed, but the appearance of other by-products did not
allow accurate determination.
time of only 7 min. We also used a domestic microwave
oven, permitting the use of a closed vessel in which high
pressures are probably reached. Under these conditions,
aromatic compounds were the only products obtained. The
best yields were obtained with the aluminum- and titanium-
immobilized catalysts, Al(Si) and Ti(Si). With regard to the
reagents, aromatization was achieved more easily with the
methyl acrylate adducts than with the acrylonitrile ad-
ducts (Table 3).
Table 3. Results obtained on treatment of 2,5-dimethylfuran (2)
with methyl acrylate (3a) and with acrylonitrile (3b), carried out in
a domestic microwave oven at 780 W in a closed Teflon vessel
Scheme 2
Dienophile
Catalyst
t [min][a]
Yield of 6 (%)[b]
have studied the reaction between 2,5-dimethylfuran and N-
methylmaleimide under microwave activation conditions in
the presence of K10-montmorillonite, and they did not ob-
serve any aromatization product.[23] It is important to note
the clear differences between a solid with strong Brønsted
acid properties, such as the K10, and the immobilized Lewis
acids used in this work. Surprisingly, with fumaronitrile the
aromatic product was not obtained, and the DielsϪAlder
cycloadduct 10 was the only product observed with all three
immobilized Lewis acids. Whereas the aromatization of the
corresponding cycloadduct was easily effected in the pres-
ence of a strong base, as described previously,[17] the same
reaction was not facile when an acid catalyst was used.
The observed differences between carbonyl and nitrile
compounds are not easy to explain, and we therefore con-
sidered it interesting to carry out some theoretical calcula-
tions on the aromatization process.
3a
SiO2
45
45
35
45
45
45
35
45
Ϫ
Zn(Si)
Al(Si)
Ti(Si)
SiO2
Zn(Si)
Al(Si)
Ti(Si)
24
64
80
Ϫ
23
50
50
3b
[a]
[b]
Final temperature: 120 °C. Ϫ
Determined by NMR using
CH2Br2 as the internal standard.
The different behavior of nitrile and carbonyl compounds
is rather surprising. We therefore decided to explore this
area further by investigating the reactions with 2,5-di-
methylfuran of a dicarbonyl dienophile, namely N-methyl-
maleimide (7), and of a dinitrile dienophile, namely fuma-
ronitrile (9) (Scheme 2), using the same immobilized Lewis
acids under microwave activation conditions. The results
obtained in these experiments are collected in Table 4.
The differences found in these reactions were very signi-
ficant. With N-methylmaleimide, high yields of the aromatic
Computational Results
The first step of the mechanism proposed for the aroma-
compound 8 were obtained, with Al(Si) and Ti(Si) once tization of the DielsϪAlder adducts consists of the
again proving to be more efficient catalysts than Zn(Si). It breaking of one of the OϪC bonds of the CϪOϪC bridge
can be seen that the differences between the two kinds of to give an intermediate zwitterion (Scheme 3). Given the
microwave activation are not due to the reaction temper- electron-withdrawing character of the CN and COOMe
ature reached, because with the focused microwave reactor groups, it would seem logical to conclude that the CϪO
lower yields were obtained even at 150 °C. Cintas et al. bond broken should be that producing the most stable zwit-
Eur. J. Org. Chem. 2001, 2891Ϫ2899
2893

A. de la Hoz, J. A. Mayoral et al.
FULL PAPER
Table 4. Results obtained on treatment of 2,5-dimethylfuran (1b) with N-methylmaleimide (7) and with fumaronitrile (9), under microwave
activation conditions
Dienophile
Catalyst
E [W] (T [°C])
t [min]
Yield of 8 (%)[a]
Yield of 10[b] (%)
7
Ti(Si)
Ti(Si)
Ti(Si)
Al(Si)
Zn(Si)
Ti(Si)
Al(Si)
Zn(Si)
780 (120)[c]
240 (90)[d]
270 (150)[d]
780 (120)[c]
780 (120)[c]
780 (120)[c]
780 (120)[c]
780 (120)[c]
45
45
45
45
45
45
45
45
80
11
55
83
50
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
60
50
20
9
Ϫ
Ϫ
[a]
[b]
Determined by NMR using CH2Br2 as the internal standard. Ϫ Determined by NMR using fumaronitrile as the internal standard.
[c]
Ϫ
Reactions carried out in a domestic microwave oven in a closed Teflon vessel; the temperature refers to the final temperature
[d]
measured. Ϫ Reactions carried out in a focused microwave reactor under 3 bar of argon.
terion, namely the one with the greater separation between of these structures were found to be higher than those cor-
the positive charge and the electron-withdrawing group responding to the DielsϪAlder cycloadduct with the Lewis
(Scheme 3). However, in the case of the acrylonitrile cyclo- acid coordinated to the cyano or carbonyl groups. Thus,
adducts, we calculated both ring-opening possibilities in or- because of the CurtinϪHammett principle,[25] these latter
der to confirm this hypothesis.
structures and energies were taken as starting points to cal-
As shown in Scheme 3, the ring-opening should be fav- culate the activation barriers of the aromatization reactions
ored by the coordination of the Lewis acid to the bridge provided that a rapid preequilibrium exists between both
oxygen atom, as should the stabilization of the final zwitter- types of complexes. In the case of the ester group, both
ion. Consequently, we calculated the structures and energies the syn and anti conformations of the carbonyl group were
of the DielsϪAlder adducts with the Lewis acid coordin- considered in the search of the corresponding transition
ated to that oxygen atom. However, in all cases the energies structures.
Structural features of the Lewis acids supported on silica
are not easy to elucidate. However, it is generally accepted
that ZnCl2 supported on silica mainly consists of very small
isolated particles of ZnCl2 dispersed on the silica surface.
On the other hand, when the silica is treated with Et2AlCl,
attachment of the Al onto the surface through reaction of
the silanol groups and displacement of the alkyl and/or
chlorine groups takes place. A recent theoretical and experi-
mental study[26] has shown that the acidity of the resulting
aluminum centers is at least as high as, if not superior to,
that of aluminum trichloride. We therefore decided to use
two simple models for the Lewis acid, namely the molecules
of ZnCl2 and AlCl3 coordinated to the corresponding cyclo-
adducts. This approach has previously been used success-
fully.[27]
Given the high number of stationary points (minima and
transition structures) that must be considered throughout
the work (see below), we explored the possibility of using a
mixed scheme of calculations. Thus, the stationary points
in the potential energy reaction surface were located at the
HF/3-21G(d) theoretical level, which has been found to be
suitable for the description of common DielsϪAlder reac-
tions.[28] Next, single point calculations were carried out at
the B3LYP/6-31G(d) theoretical level, which is known to
provide good estimates for activation barriers.[29] This
scheme has proven to give results similar to those found at
the full B3LYP/6-31G(d) theoretical level for the
DielsϪAlder reaction between 1,3-butadiene and acrolein,
both uncatalyzed and catalyzed by BF3.[30] In order to test
the validity of this scheme, some calculations were also per-
Scheme 3
2894
formed at the full B3LYP/6-31G(d) theoretical level.
Eur. J. Org. Chem. 2001, 2891Ϫ2899

Tandem DielsϪAlder Aromatization Reactions of Furans
FULL PAPER
Figure 1 and 2 show some selected structures and Table 5
collects calculated activation and relative TS energies to-
gether with some selected geometrical parameters (full de-
scription of the energy results can be obtained as Sup-
porting Information for this paper) for the ring-opening re-
actions of the cycloadducts 5a and 5b. Compounds 5a and
5b were formed from DielsϪAlder reactions between 2,5-
dimethylfuran (2) and methyl acrylate (3a) and acrylonitrile
(3b), respectively, catalyzed by ZnCl2 and AlCl3.
Figure 2. Some geometrical parameters of the transition structures
in the ring-opening reactions of cycloadducts 5b, catalyzed by
AlCl3, calculated at the HF/3-21G(d) (normal typeface) and
B3LYP/6-31G(d) (bold) theoretical levels
the cyano group is disfavored by ca. 3 kcal molϪ1 in both
cases, as one would expect from the predicted destabiliza-
tion of the incipient positive charge (Scheme 3). We will
therefore henceforth consider only the ring-opening reac-
tion through the CϪO bond situated on the side opposite
to the electron-withdrawing group.
From a structural viewpoint, it can be seen that the CϪO
distance, corresponding to the breaking bond (Table 5), is
always shorter in the case of the aluminum-catalyzed pro-
cesses than in that of the zinc-catalyzed ones. This indicates
that the TSs are earlier in the former cases, and so the cata-
lytic effect is greater with the aluminum catalyst. This trend
is also corroborated by examination of the metalϪoxygen
(MϪO) bond length (Table 5), which is always shorter for
aluminum complexes and gives rise to stronger Lewis acid
activation.
Figure 1. Some geometrical parameters of the transition structures
in the ring-opening reactions of cycloadducts 5a, catalyzed by
AlCl3, calculated at the HF/3-21G(d) (normal typeface) and
B3LYP/6-31G(d) (bold) theoretical levels
First of all, it is necessary to verify our starting hypo-
These observations are in line with the calculated energy
theses. As far as the theoretical level is concerned, it can profiles. Thus, activation barriers are always lower for alum-
easily be seen that the full B3LYP/6-31G(d) calculations inum-catalyzed reactions, a situation in agreement with the
produce activation energies very similar to those obtained experimental results and showing that aromatization reac-
at the B3LYP/6-31G(d)//HF/3-21G(d) level. Furthermore, tions are easier with Al(Si) than with Zn(Si). If one com-
the transition structures (TSs) do not display any significant pares the behavior of the two dienophiles, it can be seen
differences from a geometrical point of view. In any case, that barriers to the aromatization of ester adducts are al-
the slight geometrical differences do not result in any no- ways lower than those for nitrile adducts, a fact that is also
ticeable energy differences, as shown by the calculated relat- in good agreement with the experimental observations.
ive TS energies. We thus confirmed that the mixed scheme
proposed works well, and it was consequently used and 2,5-dimethylfuran cycloadducts, the transition struc-
throughout the work described here. tures of the aromatization reactions of the DielsϪAlder ad-
In order to compare the relative reactivity of the furan
From the mechanistic point of view, the two possibilities ducts of furan with methyl acrylates were also calculated,
for ring-opening were considered in the case of the ring- and the results are collected in Table 5. As expected, the
opening reactions of the acrylonitrile endo and exo cycload- activation barriers for the furan adducts are much higher
ducts. As can be seen, ring-opening by the CϪO bond near than those for their 2,5-dimethylfuran counterparts and are
Eur. J. Org. Chem. 2001, 2891Ϫ2899
2895

A. de la Hoz, J. A. Mayoral et al.
FULL PAPER
Table 5. Activation and relative TS energies [kcal molϪ1] along with some geometrical parameters for the Lewis acid catalyzed ring-
opening reactions of the DielsϪAlder cycloadducts of furan (1) and 2,5-dimethylfuran (2) with methyl acrylate (3a) and acrylonitrile
(3b), calculated at the B3LYP/6-31G(d)//HF/3-21G(d) and full B3LYP/6-31G(d) theoretical levels
Diene
Dienophile
Catalyst
TS
dCOϪC
dCMϪO
∆E‡ [a]
∆∆E‡
HF/3-21G(d)
B3LYP/6-31G(d)//
HF/3-21G(d)
B3LYP/6-31G(d)
B3LYP/6-31G(d)//
HF/3-21G(d)
B3LYP/6-31G(d)
2
3a
AlCl3
AlCl3
AlCl3
AlCl3
ZnCl2
ZnCl2
ZnCl2
ZnCl2
AlCl3
AlCl3
AlCl3
AlCl3
ZnCl2
ZnCl2
AlCl3
AlCl3
endo s-cis
endo s-trans 2.290
exo s-cis
exo s-trans
endo s-cis
2.346
1.756
19.1
19.1
22.1
21.9
31.9
25.5
31.1
24.7
22.5
25.8
24.0
26.8
32.4
33.6
23.3
27.7
19.0
19.7
21.1
20.6
31.4
26.2
32.1
24.8
21.9
25.2
23.3
26.1
31.3
32.1
Ϫ
0.0
0.0
2.2
2.0
4.5
5.0
0.0
2.8
0.0
2.8
2.6
2.8
0.0
2.3
0.0
2.3
0.0
0.7
1.7
2.0
4.8
4.9
0.0
2.2
0.0
3.3
2.4
3.3
0.0
2.1
Ϫ
1.759
1.746
1.744
1.821
1.819
1.885
1.858
1.763
1.761
1.763
1.824
1.823
1.822
1.760
1.757
2.403
2.378
2.507
endo s-trans 2.447
exo s-cis
exo s-trans
endo
2.574
2.554
2.322
2.354
2.329
2.416
2.485
2.498
2
3b
3a
endo[b]
exo
exo[b]
endo
exo
1
endo s-trans 2.331
exo s-trans 2.374
Ϫ
Ϫ
[a]
[b]
Values in italics correspond to the lower activation energy for a given final configuration. Ϫ Ring-opening takes place at the CϪO
bond adjacent to the CN group.
even higher than those for the adducts of 2,5-dimethylfuran
with acrylonitrile. This is in good agreement with the lack
of aromatic products observed in the reactions of the furan
adducts, and can be ascribed to the lower stabilization of
the incipient positive charge created during the ring-open-
ing process.
The next step was to compare these reactivities with
those found in the cases of N-methylmaleimide (7) and fum-
aronitrile (9). To this end, the corresponding TSs were loc-
ated at the same theoretical level for the corresponding
cycloadducts. These calculations were only performed for
catalysis by AlCl3, given that this catalyst is more active
than ZnCl2. Figure 3 shows some selected structures and
Table 6 gathers the calculated activation energies, together
with some selected geometrical parameters (full description
of the energy results can be obtained as Supporting In-
formation for this paper).
From a structural viewpoint, it can be seen that the CϪO
distance, corresponding to the breaking bond, in the case
of the N-methylmaleimide exo cycloadduct is shorter than
that calculated for the methyl acrylate exo cycloadduct, but
the reverse holds for the endo cycloadducts. The activation
barrier calculated for the endo cycloadduct is similar to
those found for the methyl acrylate cycloadducts, which is
in agreement with an easy aromatization reaction. The ac-
tivation barrier for the exo cycloadduct is slightly higher
and is similar to those found in the case of the acrylonitrile
cycloadducts Ϫ hence this is still compatible with a direct
aromatization reaction. Given the reversibility of the
Figure 3. Some geometrical parameters of the transition structures
DielsϪAlder reaction, and the irreversibility of the aroma-
tization reaction, aromatization of the exo cycloadduct by
cycloreversion and formation of the endo cycloadduct can-
not be completely discounted.
in the ring-opening reactions of the cycloadducts corresponding to
the DielsϪAlder reactions between 2,5-dimethylfuran (2) and N-
methylmaleimide (7) or fumaronitrile (9), catalyzed by AlCl3, calcu-
lated at the HF/3-21G(d) (normal typeface) and B3LYP/6-31G(d)
(bold) theoretical levels
2896
Eur. J. Org. Chem. 2001, 2891Ϫ2899

Tandem DielsϪAlder Aromatization Reactions of Furans
FULL PAPER
Table 6. Activation energies [kcal molϪ1] and some geometrical parameters for the Lewis acid catalyzed ring-opening reactions of the
DielsϪAlder cycloadducts of 2,5-dimethylfuran (2) with N-methylmaleimide (7) and fumaronitrile (9), calculated at the B3LYP/6-31G(d)//
HF/3-21G(d) and (in part) full B3LYP/6-31G(d) theoretical levels
Dienophile
Catalyst
TS
dCOϪC
HF/3-21G(d)
dCMϪO
∆E‡
B3LYP/6-31G(d)//
HF/3-21G(d)
B3LYP/6-31G(d)
7
9
AlCl3
AlCl3
AlCl3
AlCl3
endo
exo
2.405
2.369
2.350
2.408
1.754
1.761
1.770
1.767
21.6
24.8
28.7
27.8
Ϫ
Ϫ
27.8
27.0
endo[a]
exo[b]
[a] Ring-opening takes place at the CϪO bond adjacent to the endo-CN group. Ϫ [b] Ring-opening takes place at the CϪO bond adjacent
to the exo-CN group.
In the case of the ring-opening reactions of fumaronitrile Experimental Section
cycloadducts, there are two possible TSs; that in which the
cleaved CϪO bond is on the side of the endo-cyano group,
and that in which this bond is on the side of the exo-cyano
group. In neither case is there any great benefit from the
point of view of the stabilization of the transient positive
charge being formed during the bond-breaking. From the
1
General Remarks: H NMR spectra were recorded at 299.94 MHz
and 13C NMR spectra at 75.429 MHz with a Varian Unity 300
spectrometer. Chemical shifts (δ) are reported in ppm using Me4Si
as the standard internal reference, and coupling constants J are
given in Hz. Complete assignment was achieved by acquisition of
NOE difference spectra and 2D NMR correlation experiments such
geometrical point of view, if we compare the CϪO distances
corresponding to the breaking bond with those calculated
for the ring-opening of the acrylonitrile cycloadducts, it can
be seen that they are closer to those calculated for the cases
in which ring-opening takes place at the same side as the
cyano group. As a consequence, the activation barriers are
the highest calculated in this work, at 28.0 and 28.7 kcal
molϪ1, respectively. This result is in excellent agreement
with the experimental observations in terms of the experi-
mentally found difference between carbonyl and cyano
groups.
as COSY and HETCOR. Ϫ Column chromatography was carried
out with SiO2 (silica gel, Merck type 60 230Ϫ240 mesh). Ϫ Micro-
wave irradiation was conducted in a Miele Electronic M720 do-
mestic oven or a focused microwave reactor (Prolabo MX350) with
measurement and control of power and temperature by infrared
detection. Ϫ Catalysts modified with Lewis acids were obtained by
treating silica gel with 1  solutions of ZnCl2, AlEt2Cl, or TiCl4,
following the previously described method.[11Ϫ13] The silicas con-
tained 1.5 mmol of Zn gϪ1, 1.4 mmol of Al gϪ1, or 1.2 mmol of Ti
g
Ϫ1, respectively. For Zn(Si) catalyst an activation of 2 h at 150 °C
under vacuum was necessary before use. In all the reactions a diene/
dienophile molar ratio of 6:1 was used. Reagents were purchased
from commercial suppliers.
Diels؊Alder Reactions at Room Temperature: The dienophile 3a
or 3b (0.25 mmol) and the corresponding amount of furan (1) or
dimethylfuran (2) were added to the catalyst (250 mg) under argon
in a Schlenk tube. The reaction mixtures were stirred for the times
and temperatures indicated (Table 1, 3 and 4). CDCl3 (2 mL) was
added in all cases, and the catalyst was separated by filtration. The
Conclusion
Silica-supported Lewis acids are good catalysts for
DielsϪAlder reactions between furan and acrylonitrile and
methyl acrylate at room temperature. When 2,5-dimethylfu-
ran is used as a diene the yields of acrylonitrile DielsϪAlder
adducts are also very good. However, the corresponding
yields are lower with methyl acrylate and this is in part due
to the appearance of aromatization products that are not
observed with furan. The use of microwave activation in
some cases results in good yields of aromatic products and
thus constitutes a good synthetic route to polysubstituted
aromatic compounds.
Computational studies of the reaction mechanism and
the role of the catalyst on the product distribution show
that ‘‘hard’’ Lewis acids, such as aluminum derivatives,
make ring-opening of the adduct easier and result in aro-
matic products. The theoretical results are in excellent
agreement with the relative reactivities observed for the dif-
ferent cycloadducts. In particular, the different reactivities
towards aromatization exhibited by carbonyl and cyano
cycloadducts can easily be interpreted on the basis on the
energies of the corresponding transition structures for the
ring-opening reactions.
1
crude reaction mixtures were analyzed by H and 13C NMR spec-
troscopy. Yields and selectivities were determined by integration of
1
the H NMR signal of the vinyl protons [3a: δ ϭ 6.39 (Hcis); 5an:
δ ϭ 6.25 (5-H); 5ax: δ ϭ 6.32 (5-H) for reactions with methyl acryl-
ate; 3b: δ ϭ 5.63 (Hgem); 5bn: δ ϭ 6.12 (6-H); 5bx: δ ϭ 6.38 (6-H)
for reactions with acrylonitrile]. A pure mixture of endo and exo
cycloadducts was obtained by extraction of the reaction mixture
with CH2Cl2, filtration, and removal of the solvent and unchanged
reagents under reduced pressure. For reactions with methyl acryl-
ate, chromatographic separation using ‘‘end-capped’’ silica gel[15] as
a stationary phase and hexane/ethyl ether (7:3) as an eluent was
necessary.
Diels؊Alder Reactions in a Domestic Microwave Reactor: A Teflon
vessel was charged with the dienophile (3a, 3b, 7 or 9, 1.5 mmol),
the corresponding amount of dimethylfuran (2), and the catalyst
(500 mg) and then closed. The reaction mixture was irradiated in
a domestic microwave oven at 780 W for the indicated time (Table 3
and 4). In all cases, CH2Cl2 (50 mL) was added and the catalyst
was separated by filtration. The solvent was removed under re-
duced pressure and the crude reaction mixtures were analyzed by
Eur. J. Org. Chem. 2001, 2891Ϫ2899
2897

A. de la Hoz, J. A. Mayoral et al.
FULL PAPER
1H and 13C NMR spectroscopy in CDCl3. Yields were determined
by H NMR spectroscopy using CH2Br2 (δ ϭ 4.93) as an internal
6), 131.6 (C-4), 132.7 (C-3), 135.2 (C-5), 137.0 (C-2), 168.2 (COO).
1
2,5-Dimethylbenzonitrile (6b): This product was separated from the
reaction mixture as described above. Ϫ 1H NMR (CDCl3): δ ϭ
2.34 (s, 3 H, 2-CH3), 2.50 (s, 3 H, 5-CH3), 7.21 (d, J ϭ 8.3 Hz, 1
H, 3-H), 7.27 (d, J ϭ 8.3 Hz, 1 H, 4-H), 7.40 (s, 1 H, 6-H). Ϫ 13C
NMR (CDCl3): δ ϭ 19.7 (2-CH3), 20.4 (5-CH3), 112.3 (C-1), 118.1
(CN), 129.9 (C-3), 132.5 (C-6), 133.4 (C-4), 135.9 (C-5), 138.6 (C-
2).
standard. For reactions involving fumaronitrile (9) the degree of
conversion was determined using the signal at δ ϭ 6.31 from fuma-
ronitrile as the internal standard and the signal at δ ϭ 6.45 (6-H)
from the cycloadduct (10). The crude reaction mixture was purified
by flash chromatography using hexane/ethyl acetate (9:1) as eluent.
Diels؊Alder Reactions in a Focused Microwave Reactor with Tem-
perature Control: A modified FischerϪPorter reaction vessel was
charged with a mixture of the dienophile (3a or 3b, 0.25 mmol),
the corresponding amount of furan (1) or 2,5-dimethylfuran (2),
and the catalyst (250 mg). The vessel was then closed and placed
under pressure with argon (3 bar). The reaction mixtures were irra-
diated in a focused microwave reactor (Prolabo) for the time and
temperature indicated (Table 3 and 4). In all cases, CDCl3 (2 mL)
was added and the catalyst was separated by filtration. The crude
reaction mixtures were analyzed by 1H and 13C NMR spectroscopy.
Yields and selectivities were determined by integration of the 1H
NMR signals of the vinyl protons as described above.
2,4,7-Trimethylisoindole-1,3-dione (8): M.p. 168Ϫ169 °C (from hex-
1
ane). Ϫ H NMR (CDCl3): δ ϭ 2.63 (s, 6 H, 3-CH3, 6-CH3), 3.12
(s, 3 H, NCH3), 7.28 (s, 2 H, 4-H, 5-H). Ϫ 13C NMR (CDCl3): δ ϭ
17.3 (3-CH3, 6-CH3), 23.4 (NCH3), 129.0 (C-5, C-4), 135.1 (C-3,
C-6), 135.8 (8-C, 9-C), 169.2 (2 ϫ CO).
2-endo,3-exo-1,4-Dimethyl-7-oxabicyclo[2.2.1]hept-5-ene-2,3-
1
dicarbonitrile (10): Yellow oil. Ϫ H NMR (CDCl3): δ ϭ 1.79 (s, 3
H, 1-CH3), 1.80 (s, 3 H, 4-CH3), 2.89 (d, J ϭ 11.48 Hz, 1 H, Hax),
3.05 (d, J ϭ 9.28 Hz, 1 H, Heq), 6.39 (d, J ϭ 5.6 Hz, 1 H, 5-H),
6.45 (d, J ϭ 5.6 Hz, 1 H, 6-H). Ϫ 13C NMR (CDCl3): δ ϭ 16.0 (4-
CH3), 16.9 (1-CH3), 41.6 (C-2), 42.1 (C-3), 88.3 and 88.4 (C-1 and
C-4), 117.3 (2 ϫ CN), 138.9 (C-6), 139.7 (C-5).
Methyl 2-endo-1,4-Dimethyl-7-oxabicyclo[2.2.1]hept-5-ene-2-carb-
oxylate (5an): The data for this product were obtained from a mix-
ture of 5an and 5ax. Ϫ 1H NMR (CDCl3): δ ϭ 1.59 (s, 3 H, 4-
CH3), 1.73 (s, 3 H, 1-CH3), 1.83 (dd, J ϭ 11.47 and 3.91 Hz, 1 H,
3-Hax), 1.99 (dd, J ϭ 11.47 and 9.03 Hz, 1 H, 3-Heq), 2.92 (dd, J ϭ
9.03 and 3.91 Hz, 1 H, 2-H), 3.64 (s, 3 H, OCH3), 6.07 (d, J ϭ
5.61 Hz, 1 H, 6-H), 6.25 (d, J ϭ 5.61 Hz, 1 H, 5-H). Ϫ 13C NMR
(CDCl3): δ ϭ 18.5 (1-CH3), 18.7 (4-CH3), 38.3 (C-3), 51.0 (C-2),
51.6 (OCH3), 85.9 (C-4), 87.1 (C-1), 136.2 (C-6), 140.1 (C-5),
172.8 (COO).
Theoretical Calculations: Theoretical calculations were carried out
using the Gaussian 94[31] and Gaussian 98[32] programs. Geomet-
rical optimizations (minima and transition structure searches) were
performed at the HartreeϪFock theory level, using the standard 3-
21G(d) basis set and, in some cases, using a Density Functional
Theory (DFT) method based on the three-parameter hybrid cor-
relation functional developed by Becke[33] plus the
LeeϪYangϪParr[34] exchange functional (B3LYP) as implemented
in the Gaussian program, with the standard 6-31G(d) basis set. In
the case of the transition structures, frequency calculations were
carried out in order to ensure the presence on only one negative
eigenvalue of the Hessian matrix. The vibration associated with the
imaginary frequency was checked to correspond to a movement in
the direction of the reaction coordinate. Single point energy calcu-
lations were performed on the HF/3-21G(d)-optimized structures
at the B3LYP/6-31G(d) theoretical level.
Methyl
2-exo-1,4-Dimethyl-7-oxabicyclo[2.2.1]hept-5-ene-2-carb-
oxylate (5ax): The data for this product were obtained from a mix-
ture of 5ax and 5an. Ϫ 1H NMR (CDCl3): δ ϭ 1.53 (s, 3 H, 1-
CH3), 1.67 (s, 3 H, 4-CH3), 1.62Ϫ1.75 (m, 1 H, 3-Hax), 1.98Ϫ2.07
(m, 1 H, 3-Heq), 2.55 (dd, J ϭ 7.81 and 3.66 Hz, 1 H, 2-H), 3.72
(s, 3 H, OCH3), 6.15 (d, J ϭ 5.61 Hz, 1 H, 6-H), 6.21 (d, J ϭ
5.61 Hz, 1 H, 5-H). Ϫ 13C NMR (CDCl3): δ ϭ 16.3 (1-CH3), 18.5
(4-CH3), 38.3 (C-3), 49.7 (C-2), 51.6 (OCH3), 85.7 (C-4), 87.9 (C-
1), 139.1, 140.5 (C-5 and C-6), 173.9 (COO).
2-endo-1,4-Dimethyl-7-oxabicyclo[2.2.1]hept-5-ene-2-carbonitrile
(5bn): The data for this product were obtained from a mixture of
5bn and 5bx. Ϫ H NMR (CDCl3): δ ϭ 1.62 (s, 3 H, 1-CH3), 1.74
(s, 3 H, 4-CH3), 1.78 (br. s, 1 H, 3-Hax), 2.15 (dd, J ϭ 11.48 and
9.28 Hz, 3-Heq), 2.77 (dd, J ϭ 9.28 and 3.91 Hz, 1 H, 2-H), 6.31
(d, J ϭ 5.62 Hz, 1 H, 5-H), 6.38 (d, J ϭ 5.62 Hz, 1 H, 6-H). Ϫ 13C
NMR (CDCl3): δ ϭ 17.6 (4-CH3), 18.1 (1-CH3), 35.3 (C-2), 40.2
(C-3), 86.7 (C-4), 87.3 (C-1), 120.4 (CN), 136.4 (C-5), 141.0 (C-6).
Acknowledgments
This work was made possible by the generous financial support
1
´
´
of the Comision Interministerial de Ciencia y Tecnologıa (Projects
MAT99-1176 and PB97-0429). Technical assistance from Mr. Al-
fonso Saiz is also acknowledged.
[1]
R. M. Dean, Adv. Heterocycl. Chem. 1982, 30, 169.
[2]
2-exo-1,4-Dimethyl-7-oxabicyclo[2.2.1]hept-5-ene-2-carbonitrile
(5bx): The data for this product were obtained from a mixture of
P. Vogel, J. Cossy, J. Plumet, O. Arjona, Tetrahedron 1999, 55,
13521, and references cited therein.
[3]
1
W. L. Nelson, D. R. Allen, J. Heterocycl. Chem. 1972, 9, 561.
5bx and 5bn. Ϫ H NMR (CDCl3): δ ϭ 1.65 (s, 3 H, 4-CH3), 1.78
[4]
W. G. Dauben, H. O. Krabbenhoft, J. Am. Chem. Soc. 1976,
(s, 3 H, 1-CH3), 1.97Ϫ1.99 (m, 2 H, 3-Hax and 3-Heq), 2.55 (dd,
J ϭ 7.08 and 5.61 Hz, 1 H, 2-H), 6.12 (d, J ϭ 5.62 Hz, 1 H, 6-H),
6.25 (d, J ϭ 5.62 Hz, 1 H, 5-H). Ϫ 13C NMR (CDCl3): δ ϭ 16.5
(1-CH3), 18.2 (4-CH3), 35.5 (C-2), 40.3 (C-3), 85.9 (C-4), 86.8 (C-
1), 120.5 (CN), 137.3 (C-6), 140.8 (C-5).
98, 1992.
[5]
H. Kotsuki, H. Nishizawa, M. Ochi, K. Matsuoka, Bull. Chem.
Soc. Jpn. 1982, 55, 496.
[6]
F. Brion, Tetrahedron Lett. 1982, 23, 5299.
[7]
J. A. Moore, A. M. Partain III, J. Org. Chem. 1983, 48, 1105.
[8]
P. Laszlo, J. Luchetti, Tetrahedron Lett. 1984, 25, 4367.
Methyl 2,5-Dimethylbenzoate (6a): This product was separated
from the reaction mixture as described above. Ϫ 1H NMR
(CDCl3): δ ϭ 2.34 (s, 3 H, 2-CH3), 2.54 (s, 3 H, 5-CH3), 3.88 (s, 3
H, OCH3), 7.12 (d, J ϭ 7.8 Hz, 1 H, 4-H), 7.21 (dd, J ϭ 7.8 and
1.7 Hz, 1 H, 3-H), 7.70 (d, J ϭ 1.7 Hz, 1 H, 6-H). Ϫ 13C NMR
(CDCl3): δ ϭ 20.8 (2-CH3), 21.2 (5-CH3), 51.7 (OCH3), 131.0 (C-
[9]
Y. V. S. Narayama Murthi, C. N. Pillai, Synth. Commun. 1991,
21, 783.
[10]
D. A. Evans, D. M. Barnes, Tetrahedron Lett. 1997, 38, 57.
C. N. Rhodes, D. R. Brown, J. Chem. Soc., Faraday Trans.
[11]
1993, 89, 1387.
[12]
´
C. Cativiela, J. M. Fraile, J. I. Garcıa, J. A. Mayoral, E. Pires,
2898
Eur. J. Org. Chem. 2001, 2891Ϫ2899

Tandem DielsϪAlder Aromatization Reactions of Furans
FULL PAPER
[29]
[30]
[31]
`
´
´
A. J. Royo, F. Figueras, L. C. De Menorval, Tetrahedron 1993,
J. I. Garcıa, V. Martınez-Merino, J. A. Mayoral, L. Salvatella,
43, 4073.
J. Am. Chem. Soc. 1998, 120, 2415.
[13]
[14]
[15]
[16]
´
´
´
C. Cativiela, F. Figueras, J. I. Garcıa, J. A. Mayoral, E. Pires,
J. I. Garcıa, V. Martınez-Merino, J. A. Mayoral, L. Salvatella,
unpublished results.
A. J. Royo, Tetrahedron: Asymmetry 1993, 4, 621.
J. M. Fraile, J. I. Garcıa, J. Massam, J. A. Mayoral, E. Pires, J.
´
M. J. Frisch, G. W. Trucks, H. B. Schlegel, P. M. W. Gill, B. G.
Johnson, M. A. Robb, J. R. Cheeseman, T. Keith, G. A.
Petersson, J. A. Montgomery, K. Raghavachari, M. A. Al-La-
ham, V. G. Zakrzewski, J. V. Ortiz, J. B. Foresman, J. Cioslow-
ski, B. B. Stefanov, A. Nanayakkara, M. Challacombe, C. Y.
Mol. Catal. A 1997, 123, 43.
´
J. M. Fraile, J. I. Garcıa, D. Gracia, J. A. Mayoral, E. Pires, J.
Org. Chem. 1996, 61, 9479.
´
J. I. Garcıa, J. A. Mayoral, E. Pires, D. R. Brown, J. Massam,
´
Catal. Lett. 1996, 37, 261.
Peng, P. Y. Ayala, W. Chen, M. W. Wong, J. L. Andres, E. S.
[17]
[18]
[19]
M. J. Cook, S. J. Cracknell, Tetrahedron 1994, 50, 12125.
M. J. S. Dewar, A. B. Pierini, J. Am. Chem. Soc. 1984, 106, 203.
D. P. M. Mingos, A. G. Whittaker, Microwave Dielectric Heat-
ing Effects in Chemical Synthesis in Chemistry under Extreme
or Non-Classical Conditions (Eds.: R. Eldik, C. D. Hubbard),
John Wiley & Sons, New York, 1987.
F. Langa, P. de la Cruz, A. de la Hoz, A. Dıaz-Ortiz, E. Dıez-
Barra, Contemp. Org. Synth. 1997, 373.
A. Loupy, A. Petit, J. Hamelin, F. Texier-Boullet, P. Jacquault,
Replogle, R. Gomperts, R. L. Martin, D. J. Fox, J. S. Binkley,
D. J. Defrees, J. Baker, J. P. Stewart, M. Head-Gordon, C. Gon-
zalez, J. A. Pople, Gaussian 94, Revision D.3, Gaussian, Inc.,
Pittsburgh PA, 1995.
[32]
M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria, M.
A. Robb, J. R. Cheeseman, V. G. Zakrzewski, J. A. Montgom-
ery Jr., R. E. Stratmann, J. C. Burant, S. Dapprich, J. M. Mil-
lam, A. D. Daniels, K. N. Kudin, M. C. Strain, O. Farkas, J.
Tomasi, V. Barone, M. Cossi, R. Cammi, B. Mennucci, C. Po-
melli, C. Adamo, S. Clifford, J. Ochterski, G. A. Petersson, P.
Y. Ayala, Q. Cui, K. Morokuma, D. K. Malick, A. D. Rabuck,
K. Raghavachari, J. B. Foresman, J. Cioslowski, J. V. Ortiz, B.
B. Stefanov, G. Liu, A. Liashenko, P. Piskorz, I. Komaromi, R.
Gomperts, R. L. Martin, D. J. Fox, T. Keith, M. A. Al-Laham,
C. Y. Peng, A. Nanayakkara, C. Gonzalez, M. Challacombe,
[20]
[21]
´
´
´
D. Mathe, Synthesis 1998, 1213.
[22]
[23]
W. B. Wang, E. J. Roskamp, Tetrahedron Lett. 1992, 33, 7631.
M. Avalos, R. Babiano, J. L. Bravo, P. Cintas, J. L. Jimenez, J.
C. Palacios, Tetrahedron Lett. 1998, 39, 9301.
M. Sridar, K. L. Krishna, K. Srinira, J. M. Rao, Tetrahedron
Lett. 1998, 39, 6529.
D. Y. Curtin, Rec. Chem. Prog. 1954, 15, 111.
J. M. Fraile, J. I. Garcıa, J. A. Mayoral, E. Pires, L. Salvatella,
M. Ten, J. Phys. Chem. B 1999, 103, 1664.
J. M. Fraile, J. I. Garcıa, J. A. Mayoral, E. Pires, T. Tarnai,
´
[24]
[25]
[26]
´
P. M. W. Gill, B. Johnson, W. Chen, M. W. Wong, J. L. Andres,
´
M. Head-Gordon, E. S. Replogle, J. A. Pople, Gaussian 98,
Revision A.6, Gaussian, Inc., Pittsburgh PA, 1998.
A. D. Becke, J. Chem. Phys. 1993, 98, 5648.
C. Lee, W. Yang, R. Parr, Phys. Rev. B 1988, 37, 785.
Received February 20, 2001
[27]
[28]
[33]
[34]
´
Catal. Lett. 1998, 51, 235.
K. N. Houk, Y. Li, J. Evanseck, Angew. Chem. Int. Ed. Engl.
1992, 31, 682.
[O01084]
Eur. J. Org. Chem. 2001, 2891Ϫ2899
2899