Retro-diels-alder reactions of masked cyclopentadienones catalyzed by heterogeneous Bronsted acids

Article abstract of DOI:10.1002/adsc.201000571

The zeolite H-Beta catalyzes the retro-Diels-Alder reaction of a range of cyclopentadiene cyclo-adducts at moderate temperatures and ambient pressure, in the presence of an active dienophile. The active catalyst was identified and optimum reaction conditions established after screening a range of zeolites in the retro-Diels-Alder reaction of the cyclopentadiene adduct of cyclopentenone. Our results suggest that retro-Diels-Alder reactions of tricyclodecadienones are catalyzed by Bronsted acids and the high catalytic performance of H-Beta catalysts can be ascribed to the optimal balance between the number of acid sites and their strength as well as to the accessibility of these sites. The methodology was then applied to a series of alkyl derivatives of cyclopentadienylcyclopentenones to provide a viable alternative synthetic route to 4-alkylcyclopentenones and the versatility of the approach was demonstrated by the successful cycloreversion of N-cyclohexyl-2-azanorborn-5-ene. Copyright

Full text of DOI:10.1002/adsc.201000571

FULL PAPERS
DOI: 10.1002/adsc.201000571
Retro-Diels–Alder Reactions of Masked Cyclopentadienones
Catalyzed by Heterogeneous Brønsted Acids
Anneleen L. W. Demuynck,a Pieter Levecque,a,b Aklilu Kidane,c
David W. Gammon,b,* Eugene Sickle,d Pierre A. Jacobs,a Dirk E. De Vos,a
and Bert F. Selsa,*
a
Centre for Surface Chemistry and Catalysis, K. U. Leuven, Kasteelpark Arenberg 23, 3001 Heverlee, Belgium
Fax : (+32)-16-321-1998; e-mail: bert.sels@biw.kuleuven.be
Department of Chemistry, University of Cape Town, Private Bag, Rondebosch, 7701, South Africa
b
Fax : (+27)-21-689-7499; e-mail: david.gammon@uct.ac.za
Present address: PowerVision, 298 Harbor Blvd., Belmont, CA 94002, USA
Present address: Reproductive Health and HIV Research Unit, University of the Witwatersrand, Hillbrow, 2001,
c
d
South Africa
Received: July 21, 2010; Revised: October 13, 2010; Published online: December 7, 2010
Abstract: The zeolite H-Beta catalyzes the retro- number of acid sites and their strength as well as to
Diels–Alder reaction of a range of cyclopentadiene the accessibility of these sites. The methodology was
cyclo-adducts at moderate temperatures and ambient then applied to a series of alkyl derivatives of cyclo-
pressure, in the presence of an active dienophile. The pentadienylcyclopentenones to provide a viable al-
active catalyst was identified and optimum reaction ternative synthetic route to 4-alkylcyclopentenones
conditions established after screening a range of zeo- and the versatility of the approach was demonstrated
lites in the retro-Diels–Alder reaction of the cyclo- by the successful cycloreversion of N-cyclohexyl-2-
pentadiene adduct of cyclopentenone. Our results azanorborn-5-ene.
suggest that retro-Diels–Alder reactions of tricyclo-
decadienones are catalyzed by Brønsted acids and
the high catalytic performance of H-Beta catalysts Keywords: cyclopentenones; heterogeneous cataly-
can be ascribed to the optimal balance between the sis; retro-Diels–Alder reaction; zeolites
Introduction
sis of kinetically unstable compounds. The literature
is replete with examples of cycloreversion using
The retro-Diels–Alder reaction is a valuable, if little FVP,[2] but the technique has limitations associated
used, synthetic tool for unmasking an alkene moiety. with the harsh conditions, and reliance on the thermo-
The synthetic strategy generally involves a [4+2]cy- stability and volatility of the adducts.
cloaddition, followed by further synthetic modifica-
An alternative method to accomplish cyclorever-
tion of the cyclo-adduct, and finally a retro-Diels– sions utilizes Lewis acids. In particular, MeAlCl2 or
Alder reaction to regenerate the olefin. Klunder EtAlCl2 in the presence of a competing reactive
et al.[1] have highlighted the utility of this strategy, in- dieno
phile has been frequently employed,[3] with the
ACHTUNGTRENNUNG
cluding considerations of the face selectivity of the dienoCATHNUGTRNEpGUN hile present to trap the released diene. The use
Diels–Alder reaction to achieve stereochemical con- of MeAlCl2 is associated with mild reaction condi-
trol in the synthesis of functionalized cycloalkenes: tions, typically involving temperatures around 558C
masking of the substrate not only protects the double and atmospheric pressure, although there are limita-
bond, but can simultaneously convert a non-chiral cy- tions in terms of the range of substrates amenable to
cloalkadienone into a structure with stereoheterotopic this approach.[4] Microwave conditions have been em-
faces.
ployed to achieve shorter reaction times.[5] Other
Several methods have been developed to effect methods to effect cycloreversions under rather moder-
retro-Diels–Alder reactions. Among them, the use of ate conditions include the use of solid supports,[6] the
flash vacuum pyrolysis (FVP) has been the procedure adsorption of substrates on graphite under micro-
of choice. The short reaction times prevent the occur- waves,[7] and photochemical retro-Diels–Alder reac-
rence of secondary reactions and allow for the synthe- tions,[8] all with varying results.
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As the stability of the Diels–Alder adduct is depen-
dent on the nature of the diene and dienophile, an-
other strategy to facilitate the cycloreversion is to in-
troduce modifications to either component. For exam-
ple, Stꢁyer et al. constructed Diels–Alder adducts
based on furan instead of cyclopentadiene with the
expectation of subsequent easier removal of the
diene.[9] As is the case for the Diels–Alder cycloaddi-
tion, electron-withdrawing substituents on the dieno-
phile component accelerate the cycloreversion, as
confirmed by Czarnik et al. in an investigation of the
Scheme 1. Retro-Diels–Alder reaction of 2,3,3a,4,7,7a-hexa-
hydro-4,7-methano-1H-inden-1-one (1) in the presence of
maleic anhydride (2) as reactive dienophile.
cycloreversion of cycloadducts of anthracene.[10] There 608C, and a range of catalysts was screened for activi-
are also reports of fast retro-Diels–Alder reactions of ty (Table 1).
alcoholates,[11] although the major drawback of this
In the absence of catalyst, no reaction occurs in
technique is the potential for rapid racemization due CHCl3 at 608C, indicating that the cycloreversion of
to the basic conditions in which these cycloreversions adduct 1 requires considerable activation energy
proceed.[12]
(entry 1). Hence, different heterogeneous Brønsted
An important application of the retro-Diels–Alder acids were evaluated as potential catalysts, with %
reaction can be found in the synthesis of functional- yield of cyclopentenone assessed after 2.5 h and 18 h
ized cyclopentenones and cyclopentanones.[1,13] These in order to provide a broad overview of activity. In a
form an important group of structural entities present first attempt, the model reaction was accomplished
in various naturally occurring compounds, most nota- with a commercial sulfonated polymer, Nafionꢂ
bly in the prostaglandins, a class of autocrine and NR50, in hydrogen ion form (entry 2). Unfortunately,
paracrine lipid mediators which, together with their this polymer has low catalytic performance in the cy-
analogues, have a range of important pharmacological cloreversion of adduct 1. Next, we considered the use
activities.[14] Considerable effort has been devoted to of inorganic materials containing Brønsted acid sites
their synthesis[15] and where the strategies have in- as effective cycloreversion catalysts. Zeolites are crys-
volved the retro-Diels–Alder step it has been accom- talline inorganic solids with well-defined structures
plished by FVP[16] or the use of Lewis acids.[3,17] In ad- consisting of channels and cavities with molecular di-
dition, although Grieco et al. reported use of mensions. Hydrogen-exchanged zeolites, the frame-
CF3SO3H in the cycloreversion of norbornene deriva- work-bound protons of which give rise to Brønsted
tives,[17a] no further studies on the use of Brønsted acid sites, have been frequently used as catalysts in
acids in cycloreversions of this type of substrates have liquid phase conditions in the synthesis of fine chemi-
been published to date. Moreover, the application of cals.[19] Recent examples are, for instance, the cycliza-
heterogeneous catalysts in retro-Diels–Alder reac-
tions has only rarely been considered,[18] and it is thus
Table 1. Initial screening of commercial heterogeneous cata-
evident that a more general and convenient strategy
for effecting retro-Diels–Alder reactions under mild
conditions is desirable. This work therefore presents
the investigation of the use of zeolitic materials as
heterogeneous catalysts for the cycloreversion of
masked cyclopentenones.
lysts with different SiO2/Al2O3.[a]
Entry Catalyst[b]
Topology Bulk SiO2/
Al2O3
Yield
[%][c]
2.5 h 18 h
1
2
–
–
–
–
–
0
7
0
7
NafionꢂNR
50
Results and Discussion
3
4
5
6
7
8
9
10
ZF 510
Mordenite
H-BEA 25
SP6 103
CBV-720
MCM-22
CBV-760
SP6 104
FAU
8.5
10
25
26
30
30
55
82
6
7
6
7
MOR
*BEA
FAU
FAU
MWW
FAU
In the first instance, the application of heterogeneous
catalysis in retro-Diels–Alder approaches to function-
alized cyclopentenones, potential substrates for pros-
taglandin (PG) precursors, was examined (Scheme 1).
The cyclopentadiene-adduct 1 was prepared by reac-
tion of cyclopent-2-enone with cyclopentadiene in the
presence of AlCl3, and its cycloreversion to regener-
ate cyclopentenone 3 in the presence of maleic anhy-
dride (2) was investigated as a model reaction
(Scheme 1). Reactions were performed in CHCl3 at
59
12
8
10
12
9
83
45
27
26
58
22
FAU
[a]
[b]
See Experimental Section for details.
For commercial sources of zeolites, see Experimental Sec-
tion, Table 4. Note: catalysts were not dried before use.
Determined by GC with toluene as internal standard
(1 vol%); only products 3 and 4 are observed.
[c]
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Retro-Diels–Alder Reactions of Masked Cyclopentadienones
tion of small terpenoids,[19d,e] the Ferrier rearrange-
From the preliminary screening, the H-Beta zeolite
ment of protected glycals[19g] and alkyl lactate forma- H-BEA 25 appears the most promising catalyst
tion from trioses.[21c] Thus, a series of commercial zeo- (entry 5). Here, the large external surface area, origi-
lites with different SiO2/Al2O3 and different topolo- nating from the very fine crystallites (10–20 nm, for
gies, viz. FAU, *BEA, MOR and MWW was applied XRD and SEM see Experimental Section), provides
in the model reaction (entries 3–10). The ultrastable good accessibility of the catalytic sites with less mass
Y zeolite ZF 510 (entry 3) and mordenite (entry 4), transport limitations, leading to high and stable activi-
both with relatively low SiO2/Al2O3 ratios, exhibit ty in the model reaction.
some initial activity but with no increase in yield at
Our presumption that the cycloreversion of adduct
18 h of reaction. Nevertheless, with ultrastable Y zeo- 1 is catalyzed by Brønsted acids stems from Griecoꢃs
lites of the CBV and SP6 series, the yield of 2-cyclo- observation (vide supra) and other reports of cyclore-
pentenone after 18 h is significantly higher compared versions catalyzed by Brønsted acids.[20] In order to
to 2.5 h of reaction (entries 6, 7, 9, 10). This is not un- support our hypothesis and obtain more insight into
expected considering the mesoporosity in ultrastable the role of the acid strength required for efficient cy-
Y zeolite particles. Indeed, in zeolite-catalyzed syn- cloreversion of 1, the model reaction was catalyzed by
thesis of fine chemicals, diffusion limitations are often a selection of H-USY zeolites (CBV series) with in-
encountered due to the localization of active sites in creasing SiO2/Al2O3 ratios and known structural data,
micropores with dimensions too small to be reached provided by our group from previous research.[21a,c]
by bulky organic molecules. Therefore, zeolites with For subsequent experiments, all zeolites were dried at
mesopores like ultrastable Y, are likely to perform 4508C in air prior to use. As depicted in Figure 1, the
better in reactions with such molecules.
zeolites, generally show better activity in the model
reaction after drying.
More detailed results for the dried CBV series are
summarized in Table 2 (entries 1–5). In general, the
earlier observation of low activity for zeolites with
low SiO2/Al2O3 ratios is confirmed and the highest in-
itial activity is observed for CBV 720, its SiO2/Al2O3
ratio being intermediate in the range investigated. Ul-
trastable zeolites Y are prepared by hydrothermal
treatment of zeolites Y (FAU structure), resulting in
partial dealumination of the framework.[21] According
to the duration of dealumination and the nature of
subsequent washing steps, the H-USY zeolites of the
CBV series contain different SiO2/Al2O3 ratios. In
general, the higher the SiO2/Al2O3 ratio, the less
Brønsted acid sites associated with framework alumi-
nium are present in the framework, but the stronger
Figure 1. Comparison of yield of product 3 for non-dried
and dried H-USY CBV catalysts after 2.5 h reaction.
Table 2. Comparison of activity of H-USY and H-BEA zeolites with varying SiO2/Al2O3.[a]
Entry H-US Y[b]
Bulk SiO2/Al2O3 Alframework [%][c] #H+ [mmolgÀ1] Product formation rate [mmolhÀ1][d] Yield [%][d]
after 18 h
1
2
3
4
5
CBV 600
CBV 712
CBV 720
CBV 760
CBV 780
5.2
11.6
30
55
80
27
35
68
99
99
1.30
0.88
0.71
0.58
0.40
0.01
0.03
0.05
0.03
0.01
30
68
56
47
58
after 3 h
84
72
6
7
8
H-BEA 25 25
H-BEA 30 30
H-BEA 150 150
76
76
99
0.95
0.80
0.22
1.48
1.45
0.84
73
[a]
[b]
[c]
[d]
See Experimental Section for details.
For commercial sources of zeolites, see Experimental Section, Table 4. All zeolites were dried at 4508C in air prior to use.
Data available from references.[20a,c]
Determined by GC with toluene as internal standard (1 vol%); only products 3 and 4 are observed. For CBV series: aver-
age product formation rate, calculated at 2.5 h of reaction; for H-BEA series: initial product forming rate, calculated
from the linear part of the kinetic curve.
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Anneleen L. W. Demuynck et al.
FULL PAPERS
the acidity of these sites and the smaller the popula- this study. In the screening experiments, 5 mol equiva-
tion of Al species in extra-framework positions, which lents of MA were added to the reaction mixture, and
are associated with Lewis acid properties.
Figure 2 (upper panel) shows that the initial rate of
As shown in Table 2, H-USY zeolite CBV 600 the cycloreversion drops significantly when the MA/
(entry 1), with low SiO2/Al2O3 and a high proportion substrate is lowered to an equimolar ratio. Similarly,
of extra-framework aluminium, appears the least reducing the wt% of added catalyst decreases the ini-
active in the model reaction, minimizing a prominent tial rate of the cycloreversion (Figure 2, lower panel).
role of Lewis acid sites as catalytic centres. For CBV
712 and CBV 720, with decreasing number of Lewis
acid species, but increasing strength of the Brønsted
acid sites, increasing activity is observed reaching a
maximum product forming rate for CBV 720. These
observations strengthen our hypothesis of a Brønsted
acid-catalyzed model reaction and indicate that cata-
lytic sites with relatively strong Brønsted acidity are
required for efficient cycloreversion of adduct 1. For
CBV 760 and CBV 780, both with high SiO2/Al2O3
and almost no extra-framework aluminium, the initial
activity drops in comparison to CBV 720 as the
number of strong Brønsted acid sites is reduced.
The results for the H-Beta catalyst H-BEA 25
(Table 1) are consistent with our findings for the CBV
series. This catalyst, with a SiO2/Al2O3 ratio of 25 and
containing Brønsted acid sites in its micropores as
well as on the relatively large external surface,[22] dis-
plays the highest activity in the cycloreversion of
adduct 1. The H-Beta catalytic system was further ex-
plored by investigating a range of commercially avail-
able zeolites including H-BEA 25, H-BEA 30 and H-
BEA 150 (Sꢄd Chemie), where the number in each
refers to the SiO2/Al2O3 ratio (Table 2, entries 6–8).
For all H-Beta catalysts, excellent activity and high
yields are obtained. As expected from the SiO2/Al2O3
ratio, the initial product formation rates for H-BEA
25 and H-BEA 30 are significantly higher than for H-
BEA 150. Furthermore, the H-Beta series exhibits
much higher activity in the model reaction in compar-
ison with the H-USY zeolites, suggesting that a large
Figure 2. Influence of MA/1 and wt% of catalyst on the re-
action kinetics of H-BEA 25 in the model reaction.
external surface area is more beneficial to the accessi-
bility of the active sites than the presence of meso- order to guarantee that catalysis with H-BEA 25 pro-
pores. ceeds heterogeneously (see Experimental section for
Furthermore, we performed a simple experiment in
Based on this series of investigations, zeolite H- details). Regeneration of the catalyst was easily per-
BEA 25 emerged as the most promising catalyst for formed by calcination in air at 4508C.
the model reaction. Further experiments were con-
To evaluate whether part of the reagents or prod-
ducted in order to optimize the reaction parameters, ucts are strongly adsorbed in the porous catalyst, the
including the choice of solvent, the MA/substrate percentage disappearance of adduct 1 from the liquid
ratio and the wt % of catalyst required. The activity phase was compared to the percentage yield of the
of the H-Beta catalytic system in the cycloreversion product 2-cyclopentenone 3 recovered in the liquid
of adduct 1 in a range of solvents with varying polari- (Figure 3). Using GC and GC-MS analysis with tolu-
ty was thus investigated (Experimental Section, ene as internal standard, it is found that the disap-
Table 5). It was clear from these experiments that the pearance of 1 in each sample was on average about
use of apolar solvents, such as octane or toluene, was 14% higher than the yield of 3. At the same time only
detrimental to the catalytic performance of H-BEA traces (1.5% after 3 h) of the dimer of cyclopente-
25 in this reaction. With more polar solvents such as none, which is a side product, could be detected. Fur-
dioxane and ethyl acetate, better yields were ob- ther confirmation of strong adsorption on the catalyst
tained, but optimal activity was achieved in chloro- was obtained from TGA analysis on the applied cata-
form, which was thus the solvent of choice throughout lyst (60 mg), which reveals that ca. 7 mg of carbona-
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Retro-Diels–Alder Reactions of Masked Cyclopentadienones
crude reaction products by comparison of selected
signals from residual starting material and the cyclo-
pentenone product. Excellent yields in the range 92–
100% are obtained (Table 3), although, as found earli-
er in the test reaction, TGA of the used catalyst re-
veals that between 11 and 14% of reaction compo-
nents adsorbs on the catalysts.
In a further exploration of the scope of the zeolite-
catalyzed retro-Diels–Alder reactions, the cyclorever-
sion of N-alkylazanorbornenes to effect deprotection
of an amine (Scheme 3) was investigated. The imino
variant of the retro-Diels–Alder reaction has received
little attention, probably due to the harsh conditions
that are required to unmask azanorbornenes.[24] In a
notable exception, Grieco et al. introduced strategies
using moderate conditions by the use of both Brøn-
Figure 3. Comparison of the disappearance of adduct 1 (%)
from the liquid phase and the yield of 2-cyclopentenone 3
(%) in the model reaction with H-BEA 25, as determined
by GC.
AHCTUNGTRENNUNG
ceous material irreversibly adsorbs on the catalysts
after 4 h.
The foregoing results suggest that the use of H- ed solvents to facilitate direct examination of reaction
BEA 25 represents a feasible strategy in the synthesis outcomes by NMR. It was found that without addi-
of substituted cyclopentenones from suitably substi- tion of H-BEA 25 no reaction occurs in either CDCl3
tuted tricyclic ketones. A series of racemic 5-exo-sub- or dioxane-d8. However, with H-BEA 25 present in
stituted tricyclodecadienones (9a–d) was consequently CDCl3, a 51% yield of the imine (cyclohexylidene-
prepared following
a
literature procedure[23]
ACHTUNGTERNaNUNG mine) is observed, while in dioxane-d8, an acceptable
(Scheme 2) by conjugate alkylation of bicyclic enone yield (62%) of the desired amine is obtained after 3 h
8, itself prepared from dicyclopentadiene 5 via forma- of reaction at 508C, accompanied by a small amount
tion of the allylic acetate 6, followed by hydrolysis to of imine (13%). Note that in the presence of H-BEA
alcohol 7 and finally oxidation.
25, no diene-consuming agent is required to accom-
The cycloreversions of 9a–d to the corresponding 4- plish the cycloreversion of this substrate.
substituted-2-cyclopentenones 10a–d were carried out
using H-BEA 25 under optimal reaction conditions
established earlier (Table 3). The reactions were Conclusions
monitored by TLC, and when this showed no further
consumption of starting material, the relative % In summary, we have demonstrated that H-Beta zeo-
1
yields were estimated from the H NMR spectra of lites are effective heterogeneous catalysts for retro-
Scheme 2. Reaction conditions: (a) MnACTHNUTRGNE(UNG OAc)2, AcOH, Ac2O, reflux 1108C, 20 min.; then KMnO4, reflux 1108C, 30 min.;
then 5, KBr (71%), 708C, 1 h. (b) K2CO3, MeOH, room temperature, 20 h (90%). (c) PCC/alumina, hexane (90%). (d) Mg,
RBr , CuI in THF, À788C (see Experimental Section for % yields). (e) 9, maleic anhydride, zeolite, CHCl3, 608C (see Exper-
imental Section for % yields).
Adv. Synth. Catal. 2010, 352, 3419 – 3430
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Anneleen L. W. Demuynck et al.
Table 3. RDA reaction of 5-exo-substitued tricyclodecadienones 9a–d using H-BEA 25 as catalyst.[a]
FULL PAPERS
Substrate
Time [h] Product
Yield [%][b] Carbonaceous material adsorbed (mg)[c]
1
3
3
84
7.9 (66)
9a
9b
9c
8
10a
95
8.6 (78)
5
10b
10c
10d
86
11.0 (92)
16.9 (130)
16.8 (120)
5
100
92
9d
11
[a]
See Experimental Section for details, 100 wt% of catalyst was used. H-BEA 25 was dried at 4508C in air prior to use.
Determined from H NMR of product mixtures by comparison of selected signals from residual starting materials and
[b]
1
products, that is, not taking into account the material adsorbed on the zeolite surface. Note that no products other than
10a–d and MA-adduct 4 were observed.
[c]
Determined by TGA: reflects amount of carbon-containing compounds from the reaction mixture that irreversibly
adsorb on the zeolite (mg of zeolite used in parenthesis).
and 0.15M substrate. Deactivation of the catalyst ob-
served at longer reaction times is attributed to sorp-
tion limitations, but the catalyst can be regenerated
upon calcination in air. H-BEA 25 also proves active
in the imino variant of the retro-Diels–Alder reaction.
It is clear that heterogeneous catalysts are a promis-
ing alternative in selected retro-Diels–Alder reactions,
Scheme 3. Heterocycloreversion of masked primary amines.
Diels–Alder reactions of a variety of substrates under thus representing an environmentally benign alterna-
moderate conditions. The successful cycloreversion of tive to existing procedures such as FVP and the use
masked analogues of PG precursors under these con- of homogeneous Lewis acids.
ditions underlines the synthetic utility of this ap-
proach. Our results appear to support the contentions
that retro-Diels–Alder reactions can be catalyzed by
Experimental Section
Brønsted acids,[17,20] and the success of H-Beta cata-
lysts in the cycloreversion of tricyclodecadienones can
General
be ascribed to the optimal balance between the
Commercially obtained compounds were used as received.
number of active sites and the level of acidity of these
Solvents used were AR grade or dried according to
sites. The given data indicate that relatively strong
common procedures. Reaction progress was monitored by
Brønsted acidity is required for efficient catalysis. Be-
TLC. Conversions and yields were determined by integra-
sides, sufficient accessibility of these Brønsted acid
sites is also essential for good catalytic activity. Here,
the large external surface area of the small H-Beta
crystallites plays a prominent role. Excellent reaction
tion of selected signals from the 1H NMR spectra. NMR
spectra were recorded on a Bruker AMX 300 or a Varian
Mercury 300 (300 MHz) and a Varian Unity 400 (400 MHz).
MS was determined with an Agilent Technologies 6890N
rates are obtained with the use of 60 wt% H-BEA 25 GC-MS with a 30 m HP5MS column, and HR-MS was re-
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Retro-Diels–Alder Reactions of Masked Cyclopentadienones
corded on a Kratos MS50TC VG70-SEQ Micromass Mass
Spectrometer. Melting points were measured on a Reichert-
Jung Thermovar apparatus. XRD measurements were per-
formed on a STOE stadi P diffractometer using CuKa1 ra-
diation and an image plate detector covering an angular
range of 808 2q. SEM was performed on a Philips XL
FEG30 equipment.
5.7 Hz, H-8 or H-9), 5.77 (m, 1H), 5.60 (td, 1H, J=2.0 Hz,
J=5.6 Hz), 4.07 (m, 1H, H-3), 3.38 (tt, 1H, J=2.1 Hz, J=
7.0 Hz, H-6), 3.06 (m, 1H, H-1), 2.79 (m, 1H, H-7) , 2.53
(m, 1H, H-2), 1.57 (td, 1H, J=1.8 Hz, J=8.1 Hz , H-10a or
H-10b), 1.41 (s, 1H, OH), 1.39 (td, 1H, J=1.1 Hz, J=
2.0 Hz, H-10a or H-10b)
Step IIIa: Preparation of PCC: Pyridine (9.5 g) was added
over a period of 10 min to a solution of CrO3 (12 g) in 10M
HCl (22 mL) at 408C. The mixture was cooled to 108C and
stirred until a yellow-orange solid formed. The mixture was
then warmed again to 408C, whereupon the solid partly dis-
solved, and addition of a small portion of acetone achieved
complete dissolution. Alumina (100 g) was then added at
408C, the solvent evaporated under reduced pressure and
the resulting solid dried for 2 h under vacuum. The capacity
of the reagent was determined as 1.22 mmol PCC/g alumina.
Step IIIb: The alcohol 7 from step (II) was added to a
flask containing n-hexane (40 mL). PCC-alumina (35.6 g)
was then added, with the resulting mixture stirred at room
temperature until TLC analysis showed complete consump-
tion of the alcohol. The mixture was filtered over Celite, the
solid washed with n-hexane and the filtrate concentrated
under reduced pressure to give a white solid. The crude
product was purified by column chromatography on silica
gel with hexane:EtOAc (9:1) as eluent to give 8 as a white
solid; yield: 1.67 g (57%); mp 74–758C (from hexane)
(lit.[21a] mp 768C); IR: n=1692 cmÀ1 (C=O); 1H NMR
(400 MHz): d=7.36 (dd, 1H, J=2.6 Hz, J=5.7 Hz, H-5),
5.94–5.93 (m, 2H, H-8 or H-9), 5.76 (dd, 1H, J=3.0 Hz, J=
5.6 Hz, H-4), 3.39 (m, 1H, H-6), 3.20 (br m, 1H, H-7), 2.95
(br m, 1H, H-1), 2.78 (t, 1H, J=5.1 Hz, H-2), 1.74 (td, 1H,
J=1.6 Hz, J=8.4 Hz, H-10a or H-10b), 1.61 (td, 1H, J=
1.4 Hz, J=8.4 Hz); 13C NMR (100 MHz, CDCl3): d=210.5
(CO), 164.4 (C-5), 136.8 (C-4), 132.5 (C-8 or C-9), 132.3 (C-
8 or C-9), 52.6 (C-10), 50.1 (CH), 48.2 (CH), 44.9 (CH), 43.9
(CH); HR-MS: m/z=146.0737 [M+], calcd. for C10H10O:
146.0732.
Synthesis and Characterization of Substrates and
Products: 2,3,3a,4,7,7a-Hexahydro-4,7-methano-1H-
indene-1-one (1)[27]
AlCl3 (0.4 g) was introduced into a reaction flask under an
N2 atmosphere. After cooling to 08C, 2-cyclopentenone
(9.21 mL, 115 mmol) was added dropwise and then stirred
vigorously while freshly prepared cyclopentadiene (6.74 mL,
52 mmol) was added. The mixture was allowed to warm to
room temperature and stirred for 6 h. The bright yellow
mixture was then extracted with diethyl ether (2ꢅ30 mL)
and the combined organic layers were washed successively
with water, 5% aqueous NaHCO3 and brine. The organic
layer was dried over Na2SO4 and concentrated under re-
duced pressure. The crude product was purified by column
chromatography on silica gel using n-hexane/EtOAc mix-
tures (1:0 to 4:1) as eluent, to give 1 as a yellow oil; yield:
2.07 g (14%). 1H NMR (300 MHz): d=6.21 (dd, J=5.5,
2.7 Hz, 1H, H-8 or H-9), 6.12 (dd, J=5.5, 2.7 Hz, 1H, H-8
or H-9), 3.47 (dd, J=6.9, 14.1 Hz, 2H, H-7 and H-1), 3.19 (s,
1H, H-2), 2.98 (m, 1H, H-6), 2.31–1.98 (m, 3H, H-4a, H-5a,
H-10a), 1.54–1.43 (m, 2H, H-4b, H-5b), 1.23 (m, 1H, H-
10b). MS: m/z=148, 91, 83, 77, 66.
endo-Tricyclo[5.2.1.02,6]deca-4,8-diene-3-one (8)[23a,b]
Step I: Acetic anhydride (30 mL) was added to a solution of
MnACHTUNGTRENNUNG(OAc)2·4H2O (20 g) in acetic acid (80 mL). The mixture
was heated under reflux (1108C) for 20 min. KMnO4
(3.22 g) was then added portionwise to the warm solution
and the resulting mixture heated at 1108C for 30 min. After
cooling to 708C, dicyclopentadiene 5 (9.8 mL) and KBr
(1.46 g) were added with vigorous stirring and the reaction
was stirred for 1 h at 708C when the dark brown colour of
Mn(IV) had disappeared. The mixture was then cooled to
room temperature and filtered through Celite, then the fil-
trate extracted with n-hexane (100 mL) and the organic
phase washed several times with 5% aqueous NaHCO3 until
it was no longer acidic. After washing with brine the organic
phase was dried with MgSO4 and the solvent evaporated
under reduced pressure to give exo-3-acetoxydicyclopenta-
diene 6 as a colourless oil; yield: 9.4 g (68%).
Step II: K2CO3 (34.13 g) and MeOH (47 mL) were added
to 6, and the mixture was stirred at room temperature for
20 h. The resulting mixture was filtered through Celite and
the Celite washed with MeOH (50 mL), and the filtrate then
concentrated under reduced pressure. The residue was taken
up in water (50 mL), extracted with EtOAc (3ꢅ50 mL), and
the combined organic phases dried and concentrated under
reduced pressure. The crude alcohol was purified by column
chromatography on silica gel using n-hexane/EtOAc (4:1) as
eluent to give pure exo-3-hydroxydicyclopentadiene 7; yield:
3.13 g (43%). 1H NMR (400 MHz): d=5.93 (dd, 1H, J=
3.0 Hz, J=5.7 Hz, H-8 or H-9), 5.84 (dd, 1H, J=3.0 Hz, J=
exo-5-Ethyl-endo-tricyclo[5.2.1.02,6]dec-8-en-3-one
(9a)
Bromoethane (0.9 mL) was added gradually to magnesium
turnings (235 mg, 9.7 mmol) in dry THF and the mixture
was stirred until the magnesium had been consumed. Dry
CuI (60 mg, 0.32 mmol) was added to the turbid solution
and the resultant mixture stirred at 08C for 30 min, then
cooled to À788C and a solution of 8 (300 mg, 2 mmol) in
dry THF (5 mL) was added over 5 min. The mixture was
stirred for 1.5 h, then the reaction quenched by addition of
saturated NH4Cl and the product recovered by extraction
with EtOAc (3ꢅ). The combined organic phases were dried
over MgSO4 and the solvent was removed under reduced
pressure. The crude product was purified by column chro-
matography on silica gel using n-hexane:EtOAc (95:5 to
9:1) as eluent to obtain 9a as a colourless oil; yield: 270 mg
(75%). IR: n=1725 cmÀ1 (C=O); 1H NMR (400 MHz,
CDCl3): d=6.15 (m, 2H, H-8 and H-9), 3.18–3.14 (m, 1H,
H-1), 3.04–3.01 (m, 1H, H-7), 2.92 (ddd, 1H, J=2.0 Hz, J=
4.7 Hz, J=9.4 Hz, H-2), 2.62 (td, 1H, J=4.1 Hz, J=6.7 Hz,
H-6), 2.20 (dd, 1H, J=9.0 Hz, J=18.6 Hz, H-4endo), 1.92
(ddd, 1H, J=2.0 Hz, J=6.7 Hz, J=18.6 Hz, H-4exo), 1.66–
1.60 (m, 1H, H5), 1.55 (dd, 1H, J=1.6 Hz, J=8.2 Hz, H-10a
Adv. Synth. Catal. 2010, 352, 3419 – 3430
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Anneleen L. W. Demuynck et al.
FULL PAPERS
exo-5-(3-Phenylpropyl)-endo-tricyclo[5.2.1.02,6]dec-8-
en-3-one (9d)
or H-10b), 1.43 (m, 2H, CH2), 0.91 (t, 3H, J=7.3 Hz, CH3);
13C NMR (100 MHz, CDCl3): d=220.9 (CO), 136.0 (C-8 or
C-9), 135.2 (C-8 or C-9), 54.9 (C-10), 52.3 (CH), 48.5 (CH),
47.9 (CH), 47.2 (CH), 46.2 (CH), 38.5 (CH2), 30.5 (CH2),
11.9 (CH3); HR-MS: m/z=176.1201 [M+], calcd. for
C12H16O: 176.1201.
A procedure analogous to that for preparation of 9a was
used, using 1-bromo-3-phenylpropane (3.65 mL, 24 mmol),
Mg turnings (470 mg, 19 mmol), CuI (126 mg, 0.67 mmol)
and 8 (300 mg, 2 mmol). The crude product was purified by
column chromatography over silica gel with n-hexane:E-
tOAc (1:0 to 9:1) as eluent and pure 9d was obtained as a
exo-5-n-Butyl-endo-tricyclo[5.2.1.02,6]dec-8-en-3-one
light yellow oil; yield: 262 mg (48%). IR: n 1731 cmÀ1
ACHTUNGTRENNUNG(C=
O); 1H NMR (400 MHz, CDCl3): d=7.32–7.15 (m, 5H,
phenyl), 6.17 (dd, 1H, J=3.62; J=5.72, H-13a or H-13b),
5.85 (dd, 1H, J=3.23; J=5.65, H-13a or H-13b), 5.5 (dd,
1H, J=1.96; J=5.66; H-8 or H-9), 5.44 (dd, 1H, J=1.66;
J=5.66; H-8 or H-9), 3.19–3.13 (m, 1H, H-1), 3.04–2.98 (m,
1H, H-7), 2.94 (dd, 1H, J=1.88; J=4.65; H-2), 2.90 (ddd,
1H, J=1.82; J=4.66; J=4.62; H-6), 2.66–2.57 (m, 1H, H-
5); 1.96 (dd, 1H, J=1.94; J=7.02, H-4a or H-4b), 1.90 (dd,
1H, J=1.94; J=7.04; H-4a or H-4b), 1.77–1.35 (m, 6H, incl.
H-10a, H-10b, H-11a, H-11b, H-12a, H-12b); 13C NMR
(100.6 MHz, CDCl3): d=220.9 (CO), 136.2 (C-8 or C-9),
135.2 (C-8 or C-9), 128.5 (C ar.), 128.42 (C ar.), 128.37 (C
ar.), 128.3 (C ar.), 125.8 (C ar.), 54.8 (C-2), 52.3 (C-4), 48.7-
(9b)
Dry THF (10 mL) was added to a flask with CuI (817 mg,
4.3 mmol). The mixture was cooled to À58C and butyllithi-
um (5.2 mL, 1.6M in n-hexane) was added. The resulting
mixture was stirred at À58C for 15 min, after which the
flask was cooled to À788C and a solution of 8 (300 mg,
2 mmol) in dry THF (5 mL) was added slowly and the solu-
tion stirred for 2 h at À788C. The reaction was quenched by
addition of saturated aqueous NH4Cl, and the product re-
covered by extraction with ether (3ꢅ), drying of the com-
bined ether extracts over MgSO4, and removal of solvent
under reduced pressure. The crude product was purified by
column chromatography on silica gel using n-hexane:EtOAc
(9:1) as eluent to obtain 9b as a light yellow oil; yield:
357 mg (85%). IR: n=1718 cmÀ1 (C=O); 1H NMR
(400 MHz, CDCl3): d=6.14 (m, 2H, H-8 and H-9), 3.16 (m,
1H, H-1), 3.02 (m, 1H, H-7), 2.93 (ddd, 1H, J=1.9 Hz, J=
4.6 Hz, J=9.6 Hz, H-2), 2.62 (td, 1H, J=4.1 Hz, J=9.6 Hz,
H-6), 2.21 (dd, 1H, J=9.0 Hz, J=18.5 Hz, H-4endo), 1.93
(ddd, 1H, J=2.0 Hz, J=7.0 Hz, J=18.5 Hz, H-4exo), 1.71–
1.64 (m, 1H, H-5), 1.55 (d, 1H, J=8.2 Hz, H-10a), 1.41 (d,
1H, J=7.9 Hz, H-10b), 1.46–1.25 (m, 6H, (3ꢅCH2), 0.91 (t,
3H, J=6.9 Hz, (CH3); 13C NMR (100 MHz, CDCl3): d=
220.9 (CO), 136.1 (C-8 or C-9), 135.2 (C-8 or C-9), 55.6 (C-
10), 52.4 (CH), 48.2 (CH), 48.1 (CH), 46.0 (CH), 44.0 (CH),
43.9 (CH2), 33.2 (C-11), 27.1 (3ꢅCH3); HR-MS: m/z=
204.1517 [M+], calcd. for C14H20O: 204.1514.
AHCTUNGTRENG(NUN C-1), 48.3 (C-7), 47.1 (C-6), 46.1 (C-5), 37.5 (CH2), 36.8
(CH2), 35.9 (CH2), 29.4 (CH2); HR-MS: m/z=266.1708
[M+], calcd. for C19H22O: 266.1671.
4-Ethylcyclopent-2-enone (10a)[28]
A solution of 9a (200 mg, 1.14 mmol) and maleic anhydride
(0.25 g, 2.53 mmol) in 1,2-dichloroethane (5.4 mL) was treat-
ed with ethylaluminium dichloride (1.3 mL of a 1.0M solu-
tion in hexane) at ambient temperature. The solution was
stirred at 558C for 1.5 h, cooled to room temperature and
quenched with saturated aqueous NaHCO3. The solution
was extracted with ether, the solvent evaporated under re-
duced pressure, and the residue purified on silica gel (15 g,
1:9 EtOAc/hexane) to give 10a as a colourless oil; yield:
87.5 mg (60%). IR: n=1740 cmÀ1 (C=O); 1H NMR
(400 MHz, CDCl3): d=7.64 (dd, 1H, J=2.5 Hz, J=5.7 Hz,
H3), 6.15 (dd, 1H, J=2.0 Hz, 5.6 Hz, H-2), 2.88 (m, 1H, H-
4), 2.52 (dd, 1H, J=6.3 Hz, 18.8 Hz, H-5a), 2.01 (dd, 1H,
J=2.2 Hz, J=18.7 Hz, H-5b), 1.7–1.4 (m, 2H, CH2), 0.99 (t,
3H, J=7.4 Hz, CH3); 13C NMR (100 MHz, CDCl3): d=
197.6 (CO), 146.7 (C-3), 125.6 (C-2), 49.9 (C-5), 34.8 (C-4),
27.0 (CH2), 11.6 (CH3); HR-MS: m/z=110.0729 [M+], calcd.
for C7H10O: 110.0732.
exo-5-Decyl-endo-tricyclo[5.2.1.02,6]dec-8-en-3-one
(9c)
A procedure analogous to that for preparation of 9a was
used, using 1-bromodecane (6.2 mL, 28 mmol), Mg turnings
(587 mg, 24 mmol), CuI (157 mg, 0.82 mmol) and 8 (300 mg,
2 mmol). The crude product was purified by column chro-
matography over silica gel with n-hexane:EtOAc (1:0 to
95:5) as eluent and pure 9c was obtained as a light yellow
4-Butylcyclopent-2-enone (10b)
1
oil; yield: 538 mg (91%). IR: n=1734 cmÀ1
(C=O); H NMR
(400 MHz, CDCl3): d=6.15 (m, 2H, H-8 and H-9), 3.17 (m,
1H, H-1), 3.03 (m, 1H, H-7), 2.93 (ddd, 1H, J=1.9 Hz, J=
4.7 Hz, J=9.6 Hz, H-2), 2.62 (td, 1H, J=4.1 Hz, J=9.7 Hz,
H-6), 2.21 (dd, 1H, J=9.0 Hz, J=18.6 Hz, H-4endo), 1.93
(ddd, 1H, J=2.0 Hz, J=6.7 Hz, J=18.6 Hz, H-4exo), 1.63
(m, 1H, H5), 1.56 (d, 1H, J=8.2 Hz, H-10a), 1.26 (dd, 1H,
J=6.3 Hz, J=7.9 Hz, H-10b), 1.44 (m, 18H, 9ꢅCH2), 0.92
(t, 3H, J=7.3 Hz, CH3); 13C NMR (100 MHz, CDCl3): d=
136.2 (C-8 or C-9), 135.3 (C-8 or C-9), 54.9 (C-2), 52.4 (C-
4), 48.9 (C-1), 48.4 (C-7), 47.2 (C-6), 46.2 (C-5), 38.0 (CH2),
36.9 (CH2), 31.9 (CH2), 29.7 (CH2), 29.6 (CH2), 29.6 (CH2),
29.4 (CH2), 27.6 (CH2), 22.7 (CH2), 14.1 (CH3); m/z=
288.2447 [M+], calcd. for C20H32O: 288.2453.
A solution of 9b (200 mg, 0.98 mmol) and maleic anhydride
(0.15 g, 1.47 mmol) in 1,2-dichloroethane (10 mL) was treat-
ed with ethylaluminium dichloride (1.1 mL of a 1.0M solu-
tion in hexane) at ambient temperature. The solution was
stirred at 558C for 1.5 h, cooled to room temperature and
quenched with saturated aqueous NaHCO3. The solution
was extracted with ether, the solvent evaporated under re-
duced pressure, and the residue purified on silica gel (10 g,
1:20 EtOAc/hexane) to give 10b as a light yellow oil; yield:
108 mg (80%). IR: n=1750 cmÀ1 (C=O); 1H NMR
(400 MHz, CDCl3): d=7.64 (dd, 1H, J=2.5 Hz, J=5.7 Hz,
H3), 6.14 (dd, 1H, J=2.0 Hz, J=5.7 Hz, H-2), 2.96–2.88 (m,
1H, H-4), 2.53 (dd, 1H, J=6.3 Hz, J=18.8 Hz, H-5a), 2.01
3426
asc.wiley-vch.de
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2010, 352, 3419 – 3430

Retro-Diels–Alder Reactions of Masked Cyclopentadienones
(dd, 1H, J=2.2 Hz, J=18.8 Hz, H-5b), 1.65–1.25 (m, 6H,
3ꢅCH2), 0.92 (t, 3H, J=7.2 Hz, CH3); 13C NMR (100 MHz,
CDCl3): d=209.9 (CO), 168.5 (C-3), 133.5 (C-2), 41.4 (C-4),
40.9 (C-5), 34.4 (CH2), 29.7 (CH2), 22.6 (CH2), 13.8 (CH3);
HR-MS: m/z=138.1035, [M+], calcd. for C9H14O: 138.1045.
acid present. The yellow solution was extracted once more
with Et2O (3ꢅ25 mL). The combined organic layers were
dried with K2CO3 and the solvent was evaporated under re-
duced pressure to obtain 11 as a yellow oil; yield: 3.53 g
1
(78%). H NMR (300 MHz): d=6.27 (d, J=5.5, 1H, H-3),
5.95 (d, J=5.5, 1H, H-4), 4.08 (s, 1H, H-5), 3.18–3.14 (dd,
J=8.2, J=2.8, 1H, H-1a), 2.88 (s, 1H, H-2), 2.04–1.97 (m,
1H, H-1b), 1.76–1.13 (m, 13H, H-6, H-8, H-9, H-10, H-11,
H-12), 1.54 (d, J=8.2, 1H, H-7).
4-Decylcyclopent-2-enone (10c)
A solution of 9c (200 mg, 0.69 mmol) and maleic anhydride
(0.33 g, 3.35 mmol) in 1,2-dichloroethane (10 mL) was treat-
ed with ethylaluminium dichloride (1.0 mL of a 1.0M solu-
tion in hexane) at ambient temperature. The solution was
stirred at 558C for 1.5 h, cooled to room temperature and
quenched with saturated aqueous NaHCO3. The solution
was extracted with ether, the solvent evaporated under re-
duced pressure, and the residue purified on silica gel (10 g,
1:20 EtOAc/hexane) to give 10c as a colourless oil; yield:
122 mg (80%). IR: n=1717 cmÀ1 (C=O); 1H NMR
(400 MHz): d=7,63 (dd, 1H, J=2.5 Hz, J=5.7 Hz, H-3),
6,14 (dd, 1H, J=2.0 Hz, J=5.7 Hz, H-2), 2.91 (m, 1H, H-4),
2.53 (dd, 1H, J=6.3 Hz, J=18.8 Hz, H-5a), 2.00 (dd, 1H,
J=2.2 Hz, J=18.8 Hz, H-5b), 1.35 (m, 18H, 9ꢅCH2), 0.89
(t, 3H, J=6.9 Hz, CH3); 13C NMR (100 MHz, CDCl3): d=
210.0 (CO), 168.6 (C-3), 133.6 (C-2), 41.6 (C-4), 41.1 (C-5),
34.8 (CH2), 31.9 (CH2), 29.7 (CH2), 29.6 (CH2), 29.5 (CH2),
29.3 (CH2), 27.7 (CH2), 22.7 (CH2), 14.1 (CH3); HR-MS:
m/z=222.2006 [M+], calcd. for C15H26O: 222.1984.
Heterogeneous Catalysis; Commercial Sources of
Zeolites (Table 4)
Procedure for preparation of MCM-22: Into a 1-L beaker
were charged 1.21 g NaOH and 1.01 g Na-aluminate. 257.8 g
of distilled water were added and the mixture was stirred.
Then 11.17 g hexamethyleneimine and 19.10 g aerosil 200
were added and the mixture was stirred for ca. 30 min. The
gel was charged into an autoclave. The gel was rotated at
1508C during 9 to 10 days and then removed from the auto-
clave. The gel was filtered on a Buchner filter. After drying
at 608C and calcination at 5808C until the powder was
white, it was refluxed for ca. 4 h as a solution of ca. 3 g
powder, 15 g NH4Cl and 500 mL water. The mixture was
centrifuged, the powder dissolved in 500 mL water, 15 g
NH4Cl were added and the mixture was refluxed again.
After centrifugation and drying at 608C the resulting zeolite
was calcined for about 16 h at 4508C (18CminÀ1, O2 gas)
and cooled down.
4-(3-Phenylpropyl)-cyclopent-2-enone (10d)
A solution of 9d (200 mg, 0.75 mmol) and maleic anhydride
(0.40 g, 4.05 mmol) in 1,2-dichloroethane (10 mL) was treat-
ed with ethylaluminium dichloride (0.8 mL of a 1.0M solu-
tion in hexane) at ambient temperature. The solution was
stirred at 558C for 1.5 h, cooled to room temperature and
quenched with saturated aqueous NaHCO3. The solution
was extracted with ether, the solvent evaporated under re-
duced pressure, and the residue purified on silica gel (10 g,
1:20 EtOAc/hexane) to give 10d as a pale yellow oil; yield:
100 mg (67%). IR: n=1713 cmÀ1 (C=O); 1H NMR
(400 MHz, CDCl3): d=7.61 (dd, 1H, J=2.5 Hz, 5.7 Hz, H-
3), 7.29 (dd, 2H, J=5.5 Hz, 13.0 Hz, ar. H m), 7.19 (dd, 3H,
J=7.4 Hz, 14.1 Hz, ar. H p and o), 6.14 (dd, 1H, J=2.0 Hz,
J=5.7 Hz, H-2), 2.94 (m, 1H, H-4), 2.66 (t, 2H, J=7.4 Hz,
-CH2Ph), 2.53 (dd, 1H, J=6.3 Hz, 18.8 Hz, H5a), 2.00 (dd,
1H, J=2.2 Hz, 18.8 Hz, H-5b), 1.58 (m, 4H, 2ꢅCH2);
13C NMR (100 MHz, CDCl3): d=168.2 (C-3), 133.8 (C-2),
128.5 (C ar.), 128.4 (C ar.), 126.0 (C ar.), 41.4 (C-5), 41.0 (C-
4), 35.9 (CH2), 34.3 (CH2), 29.4 (CH2); HR-MS: m/z=
200.1192 [M+], calcd. for C14H16O: 200.1201.
Screening Reactions
(a) Screening reactions with adduct (1) and tricyclodecadi-
enones (9a–d): Ketone (0.45 mmol), maleic anhydride
(5 equiv), CHCl3 (3 mL) and catalyst were combined in a
10-mL screwcap vial. The vial was closed tightly and heated
with stirring at 608C.
(b) Reactions of N-cyclohexyl-2-azanorborn-5-ene (11) in
deuterated solvents: Adduct 11 (0.25M), CDCl3 or dioxane-
d8 (3 mL) and catalyst (dried at 4508C in air, 100 wt%
against substrate) were combined in a 10-mL screwcap vial.
The vial was closed tightly and the mixture stirred at 508C.
(c) Solvent screening: (see Table 5).
Table 4. Commercial sources of used zeolites.
Name
Topology SiO2/Al2O3 Commercial source
CBV-600
CBV-712
CBV-720
CBV-760
CBV-780
ZF 510
SP6 103
SP6 104
H-BEA 25
H-BEA 30
FAU
FAU
FAU
FAU
FAU
FAU
FAU
FAU
*BEA
*BEA
5.2
11.6
30
55
80
8.5
26
82
25
30
PQ zeolites
PQ zeolites
PQ zeolites
PQ zeolites
PQ zeolites
Zꢆocat
N-Cyclohexyl-2-azanorborn-5-ene (11)[29]
Cyclohexylamine was mixed with EtOH followed by addi-
tion of HCl. Upon dropwise addition of THF, cyclohexyl-
ACHTUNGTRENNUNGamine hydrochloride precipitated as white crystals and THF
and EtOH were removed under reduced pressure. The crys-
tals (3.46 g) were dissolved in H2O (10 mL) and formalde-
hyde (2.7 mL) was added followed by the addition of cyclo-
pentadiene (3.5 mL). The mixture was stirred for 5 h at
room temperature, diluted with H2O (20 mL) and extracted
with Et2O (2ꢅ20 mL). The pH of the aqueous layer was in-
creased by addition of KOH (4 g) in order to neutralize the
Grace Ghmb
Grace Ghmb
Sꢄd Chemie
Sꢄd Chemie
Sꢄd Chemie
Zeolon
H-BEA 150 *BEA
150
10
30
Mordenite
MCM-22
MOR
MWW
See procedure[a]
[a]
Procedure for preparation of MCM-22.
Adv. Synth. Catal. 2010, 352, 3419 – 3430
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
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Anneleen L. W. Demuynck et al.
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Table 5. Cycloreversion of the adduct 1 in different sol-
ACHTUNGTRENNUNG
vents.[a]
Solvent
Yield [%][b]
2.5 h
18 h
chloroform
dioxane
ethyl acetate
acetonitrille
THF
59
40
29
45
7
28
3
12
83
54
55
20
28
26
20
7
ethanol
toluene[c]
octane[d]
[a]
Reaction conditions: 0.45 mmol adduct 1, 5 mol equiva-
lents maleic acid anhydride, 60 mg catalyst (non-dried),
608C.
Determined by GC with 1 vol% toluene as internal stan-
dard.
[b]
[c]
[d]
Dioxane as internal standard.
Substrate only partly dissolves in octane.
X-Ray Diffraction (XRD) (Figure 4)
XRD measurements were performed on a STOE stadi P dif-
fractometer using CuKa1 radiation and an image plate de-
tector covering an angular range of 808 2q. A small amount
of H-Beta crystals were put on a mylar film. Measurement
times were 500 s.
The H-Beta crystallite size was estimated from the peak
at 22.358 2q using the Debye-Sherrer relationship: (i) k=
shape factor=~0.9; (ii) l=X-ray wavelength=1.54 Ang-
strçm; (iii) b=FWHM; (iv) q=Bragg angle=11.1798. For
calculation of b, a correction of 0.15 degrees is required due
to the geometrical set up of the equipment. For H-BEA 25
an average crystallite size of 16.8 nm was obtained.
Figure 5. SEM photographs of H-BEA 25.
Test for Heterogeneous Catalysis
In order to guarantee that catalysis with H-BEA 25 pro-
ceeds heterogeneously, the following experiment was per-
formed. Adduct
1 (0.45 mmol) and maleic anhydride
(5 equiv.) were added to H-BEA 25 (60 mg) in CHCl3
(3 mL). The resulting mixture was stirred at 608C for a
couple of minutes. Then, the mixture was centrifuged to de-
posit the solid catalyst. The supernatant solution was filtered
(Ø 200 nm) and analyzed by GC (product yield 3, 17%).
The filtrate was further stirred at 608C and samples were
taken after 1, 2 and 5 h. GC analysis of these samples
showed that the yield of product 3 was not further in-
creased. Therefore, we can conclude that catalysis with H-
BEA 25 occurs heterogeneously.
Scanning Electron Microscopy (SEM) (Figure 5)
SEM was performed on a Philips XL FEG30 equipment to
visualize the morphology of the H-Beta zeolites samples.
Acknowledgements
This research was supported by the National Research Foun-
dation (South Africa) and the Flemish Government (Bilateral
Scientific Cooperation). The authors also acknowledge a Me-
thusalem grant for long term support by the Flemish Govern-
ment, IAP project 6/27 (Belgian Federal Government), the
Claude Leon Foundation (South Africa), and the University
of Cape Town for funding.
Figure 4. XRD measurement of H-BEA 25.
3428
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ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2010, 352, 3419 – 3430

Retro-Diels–Alder Reactions of Masked Cyclopentadienones
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