Lewis acid catalyzed conjugate addition and the formation of heterocycles using Michael acceptors under solvent-free conditions

Article abstract of DOI:10.1002/ejoc.200500923

Conjugate addition and conjugate-addition-initiated ring closure (CAIRC) reactions of β-dicarbonyl compounds with Michael acceptors have been studied using several Lewis acid catalysts under solvent-free conditions. Excellent chemoselectivity was obtained when various Michael acceptors were treated with several β-dicarbonyl compounds. On the other hand, 2-bromo-2-cyclopentenone and 3-bromo-3-vinyl methyl ketone furnished 2,3-dihydrofurans instead of the 1,4-adducts when treated with the same reagents. Wiley-VCH Verlag GmbH & Co. KGaA, 2006.

Full text of DOI:10.1002/ejoc.200500923

FULL PAPER
DOI: 10.1002/ejoc.200500923
Lewis Acid Catalyzed Conjugate Addition and the Formation of Heterocycles
using Michael Acceptors under Solvent-Free Conditions
[a]
[a]
Alemayehu Mekonnen and Rolf Carlson*
Keywords: β-Dicarbonyl compounds / Dihydrofurans / Conjugate addition / Lewis acid catalysis / Dionato complexes
Conjugate addition and conjugate-addition-initiated ring
closure (CAIRC) reactions of β-dicarbonyl compounds with
Michael acceptors have been studied using several Lewis
acid catalysts under solvent-free conditions. Excellent
chemoselectivity was obtained when various Michael ac-
ceptors were treated with several β-dicarbonyl compounds.
On the other hand, 2-bromo-2-cyclopentenone and 3-bromo-
3-vinyl methyl ketone furnished 2,3-dihydrofurans instead of
the 1,4-adducts when treated with the same reagents.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2006)
cluding ultrasound and microwaves.[17] However, to the best
of our knowledge, there are very few studies on the Lewis
acid catalyzed addition of β-dicarbonyl compounds to
Michael acceptors under solvent-free conditions. Besides,
most of these Lewis acids rarely show a wide range of effi-
ciency over various β-dicarbonyl compounds. In most cases,
surveys were carried out on β-keto esters, and application
to other functionalities such as β-diesters and β-diketones
Introduction
The conjugate addition of β-dicarbonyl compounds to
activated π-systems is one of the most useful C–C bond-
forming methods in organic synthesis.[1] Traditionally, these
reactions have been catalyzed by bases such as alkali metal
alkoxides or hydroxides that may generate byproducts due
to competing side reactions.[ Therefore, the catalysis by
transition metals or lanthanides, which work under neutral
2]
have not been extensively investigated. For instance, Kot-
and mild conditions, has attracted the attention of the
[18]
suki et al.
reported the TfOH-catalyzed 1,4-addition re-
chemical community.[
3,4]
Conjugate addition of β-dicar-
actions of β-keto esters with Michael acceptors under neat
conditions. Microwave-irradiation-assisted 1,4-additions of
bonyl compounds, especially β-keto esters, to several ac-
[
2]
[5]
ceptors catalyzed by LiI, zeolite, non-ionic bases such
β-dicarbonyl compounds to enones mediated by BiCl ,
3
as phosphazenes and guanidines,[ indium metal/TMSCl,
6]
[7]
[19,20]
EuCl or CdI have also been investigated.
More re-
3
2
[
8–10]
some copper and nickel compounds,
Yb(OTf)3 in
[17]
cently, Yadav et al. reported the conjugate addition of β-
[
11]
[12]
H O
or silica gel support,
and Lewis acid/surfactant systems have been re-
clay-supported NiCl /
2
2
keto esters to Michael acceptors mediated by InCl .
3
[
13]
[14]
FeCl3
[21]
Christoffers
also developed an FeCl ·6H O-catalyzed
3 2
ported. As a consequence of the ever-increasing demand for
optically active compounds, asymmetric versions have also
been investigated using either chiral complexes of metal cat-
ions or organo-catalysts.[
Michael addition of β-keto esters to enones without sol-
[22]
vent. In a paper by Bartoli et al.
β-dicarbonyl com-
pounds were treated with Michael acceptors in the presence
15,16]
of CeCl ·7H O/NaI to afford effectively 1,4-addition under
3
2
However, most conjugate-addition and conjugate-ad-
dition-initiated ring-closure (CAIRC) reactions reported so
far are performed in solution, either in aqueous or non-
aqueous media. Recently, for environmental and economic
reasons, attention has focused on catalytic reactions under
solvent-free conditions. The reactions carried out either in
water or under solvent-free methods are much sought for,
as they can also be employed with noticeable increase in
reactivity and selectivity.[ Solventless techniques represent
clean, economical, efficient and safe procedure that can be
efficiently coupled to nonclassical methods of activation in-
solvent-free conditions.
However, catalysts that display broad functional group
tolerance, enhanced reaction rates and high turnover num-
[23]
bers for an intermolecular addition are rare.
Thus, the
metal-catalyzed conjugate addition of nucleophiles to acti-
vated olefins is still a largely unsolved, but synthetically im-
portant problem. In this paper we report our findings on
Lewis acid catalyzed conjugate-addition and CAIRC reac-
tions with the use of Michael acceptors (Figure 1). The first
part will describe a mild and efficient strategy for conjugate
addition of β-dicarbonyl compounds (Figure 2) to 2-cyclo-
pentenone (1a). A plausible reaction mechanism which is
consistent with our experimental data will be suggested. Fi-
nally, the second part will discuss the application of this
catalytic process in the formation of heterocycles from β-
17]
[
a] Department of Chemistry, University of Tromsø,
9
037 Tromsø, Norway
Fax: +47-776-44737
E-mail: rolf.carlson@chem.uit.no
Eur. J. Org. Chem. 2006, 2005–2013
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2005

A. Mekonnen, R. Carlson
FULL PAPER
dicarbonyl compounds to 2-bromoalkenones under the β-dicarbonyl compounds and 1a in the presence of
same reaction conditions.
FeCl ·6H O gave good results under solvent-free condi-
3 2
tions. For instance, when 1a was treated with 2a in the pres-
ence of FeCl ·6H O, 3a was isolated in 69% yield.
3
2
Figure 1. α,β-Unsaturated ketones 1a–1e used as Michael ac-
ceptors.
Scheme 2.
With these inspiring results in hand, we decided to survey
other types of Lewis acids under the same reaction condi-
tions. In these experiments, 1a, 1d and 2a were selected as
model reactants. A series of commercially available Lewis
acids with different complexation ability, such as Sc(OTf)3,
Cu(OTf) , In(OTf) , Zn(OTf) , FeCl ·6H O, Bi(NO ) ·
2
3
2
3
2
3 3
5
H O, AgOTf, CoCl ·6H O, Ni(NO ) ·6H O and MnCl ,
2 2 2 3 2 2 2
were surveyed for their ability to induce conjugate addition
Figure 2. Michael donors 2 used in conjugate-addition and CAIRC
reactions.
of β-dicarbonyl compounds to 1a. In the screening experi-
II
III
III
II
ments, the triflates of Cu , Sc , In , Zn and Bi(NO ) ·
3
3
5
H O were found to be extraordinarily effective catalysts
2
(
Table 1). On the other hand, none or only trace amounts of
the expected products were detected when AgOTf, MnCl2,
Ni(NO ) ·6H O and CoCl ·6H O were used. So far, there
Result and Discussion
As part of a project on the synthetic use of α-donor-α,β-
unsaturated ketones, 2-bromo-2-cyclopentenone (1d) has
been of particular interest as a potentially useful synthetic
intermediate. Therefore, this study was primarily designed
to investigate the effect of Lewis acid catalysts on the reac-
tion of β-dicarbonyl compounds with the α-bromoalk-
enones 1d and 1e under solvent-free reaction conditions, so
that an environmentally benign procedure could be ob-
tained. As an initial attempt, we treated 1d with 2a in the
3 2
2
2
2
is no report on the conjugate addition reactions of β-dicar-
bonyl compounds with Michael acceptors mediated by tri-
II
III
III
II
flates of Cu , Sc , In , Zn and Bi(NO ) ·5H O under
3 3
2
solvent-free conditions.
Following a screening experiment, further investigations
were done to identify the appropriate reaction conditions
with the model reactants 1a and 2a. The results indicated
that the donor/acceptor ratio as well as the catalysts used,
strongly influenced the yields of the desired products. For
each of the reactions studied, the yields of the Lewis acid
catalyzed reaction fluctuates in a surprisingly consistent
fashion as the reactant ratios and metal catalysts were var-
ied. Although, from a mechanistic point of view, little is
known about the real catalytic function of the Lewis acids,
during our investigation we have found that the highest
catalytic activity was achieved when 10 mol-% of metal ion
was employed. Consequently, the effect of the stoichiomet-
ric amount of reactants on the yield of 3a was also investi-
gated in the presence of 10 mol-% of Lewis acid. When an
presence of Zn(OTf) (Scheme 1, path A), and we obtained
2
significant amounts of the corresponding dihydrofuran ad-
ducts through the CAIRC reaction.
Scheme 1.
However, when we searched for further information on acceptor/donor ratio of 1:3 was used, the conversion rate
this type of reaction, we found reports stating that the con- was retarded and the yield was decreased. On the other
jugate addition of β-keto esters to enones catalyzed by hand, when equimolar amounts of 1a and 2a were used,
FeCl ·6H O is only possible if the enone could adopt the excess 1a was recovered (Scheme 2). Both conversion rate
3
2
cisoid conformation.[ According to these papers, com- and yield improved significantly when an acceptor/donor
21]
pounds such as 2-cyclopentenone (1a), which can not adopt ratio of 1:2 was employed.
a favorable conformation, should therefore be reluctant to
On the basis of the above results, we also examined the
undergo Lewis acid catalyzed reactions (Scheme 1, path B). generality of our Lewis acid catalyzed version in the context
Thus, these reports forced us to change our strategy and of the 1,4-addition of several β-dicarbonyl compounds such
also to include 1a in our study. Nevertheless, as indicated as β-keto esters, β-diketones and β-diesters to 1a using the
in Scheme 2 and Table 1, the reaction between several above-mentioned conditions. Several examples that demon-
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Heterocycles by Catalyzed Conjugate Addition using Michael Acceptors
FULL PAPER
Table 1. Solvent-free Lewis acid catalyzed conjugate-addition reaction of the β-dicarbonyl compounds 2a–l with the Michael acceptor 1a
at room temperature.
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2007

A. Mekonnen, R. Carlson
FULL PAPER
Table 1. (continued).
[a] n.d.: not determined.
strate the general feasibility of the present method are
Generally, the metal triflates showed strong and almost
shown in Table 1. For instance, 1a reacted with various acy- unvarying reactivity to a wide range of β-dicarbonyl com-
III
clic β-dicarbonyl compounds in high yields (Table 1, En- pounds. In also showed a similar catalytic behavior to
III
III
tries 1–5), and even with cyclic β-dicarbonyl compounds, that of the transition metal triflates, whereas Fe and Bi
reasonable yields of the desired products were obtained were variable. For instance, as it is indicated in Table 1 (En-
III
(
Table 1, Entries 6–10). Some interesting compounds such tries 9 and 10), Bi showed a strong catalytic activity
as 3k and 3l were also isolated from the 1,2-diketone 2k towards the reactions of 2i and 2j with 1a, whereas it was
and the lactone 2l, respectively. These results clearly reflect a relatively poor catalyst for the reaction of other β-dicar-
the general and remarkable activity of these catalysts, espe- bonyl compounds. This clearly suggested that the mode of
II
II
III
III
III
cially the triflates of Cu , Zn , Sc and In . Although interaction of the Bi -mediated process is different from
FeCl ·6H O is generally regarded as good catalyst, it is not that of other catalysts. Furthermore, the failure of other
3
2
as effective as other Lewis acids in terms of reactivity and salts to promote an effective Michael reaction also indicates
selectivity. their inability to produce a precise coordinating complex or
The β-diketones showed slightly lesser reactivity than the other intermediates that are critical for the success of the
β-keto esters. Particularly when 2h, 2i and 2j were used reaction. This can be connected with the charge/size ratio
[
24]
(
Table 1, Entries 8, 9 and 10), a large amount of starting and hydrolysis constants of the metal ions. For instance,
I
material remained unreacted, even after prolonged reaction the oxophilicity of Ag is significantly lower than that of
times. The generality of the catalytic process was also fur- other ions, as a result of a lower charge/size ratio of the ion.
ther demonstrated by carrying out the Michael addition of Ni(NO ) ·6H O and CoCl ·6H O were found to loose their
3
2
2
2
2
β-diesters such as 2d and 2e to 1a (Table 1, Entries 4 and activity possibly because of the hydrolytic decomposition in
). Though the catalysts display a wide range of structural the presence of trace amounts of moisture, which indicates
variations of β-dicarbonyl compounds, the reaction be- the sensitivity of these ions to non-anhydrous conditions.
comes slower and needs a longer time for completion when We have also found that the catalytic activity is highly
5
β-diesters were used. Moreover, no or trace amounts of dependent upon the purity of the Lewis acids used. Another
products were observed when the reaction was catalyzed by observation was that there was no reaction at all or only
Bi(NO ) ·5H O (Table 1, Entries 4 and 5). When β-keto es- trace amounts of products could be isolated when the reac-
3
3
2
ters or β-diesters were treated with 1a in the presence of tion was performed in the presence of a solvent such as
FeCl ·6H O and Bi(NO ) ·5H O, the desired products were CH CN. The loss of catalytic activity in the presence of a
3
2
3 3
2
3
isolated along with decarboxylated side products as de- solvent is possibly due to the competitive coordination of
tected by GC-MS. the solvent to the catalyst which hinders the formation of
2008
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Heterocycles by Catalyzed Conjugate Addition using Michael Acceptors
FULL PAPER
the complex. This competition could also mask the weak of special selectivities. In this catalytic process stirring has
interactions that lead to further consequences on the reac- no significant effect on the rate of conversion.
tivity and selectivity. In other words, the interaction be-
The mechanism for the addition of metal enolates to
tween the reactants could be increased when solvent-free or Michael acceptors has been investigated by several au-
[
6,8,21b]
aggregated charged species are involved, which results in a thors.
It has been suggested that metal enolates of β-
decrease in molecular dynamics and subsequent induction dicarbonyl compounds of the general structure I (Figure 3),
formed in situ, are the actual nucleophilic species.[ Al-
6]
though the formation of the dionato complex I is a gen-
Figure 3. Possible structures of metal enolate intermediates.
Scheme 3.
Table 2. Solvent-free Lewis acid catalyzed conjugate addition reaction of β-dicarbonyl compounds with Michael acceptors 1b and 1c to
give 4 and 5, respectively, at room temperature.
[a] n.d.: not determined.
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A. Mekonnen, R. Carlson
FULL PAPER
erally accepted principle for transition- and main-group-
[
6,8]
metal cations,
the attack on the Michael acceptor by the
complex is yet an unresolved issue and requires further re-
search.
However, the simultaneous coordination of both reac-
tants to the metal center has been suggested.[
21b,21c]
This
proposal gives great emphasis to the conformation of the
Michael acceptor. If both reagents are simultaneously coor-
dinated in the intermolecular reaction, the Michael ac-
ceptor should adopt an s-cis conformation as in II (Fig-
ure 3). This automatically excludes some enones that can
not form this favorable conformation.
In order to shed some light on the role of the substrate
structure upon the Lewis acid catalysis, other acceptors
such as 1b and 1c were also included in our study as shown
in Scheme 3 and Table 2. Comparison of the results of
Table 1 with those of Table 2 help us to propose some struc-
ture–reactivity relationships among different Michael ac-
ceptors. The fact that there was a small difference among
the acceptors in terms of isolated yields, we do not consider
this to be chemically significant. Particularly, 1a, which was
considered to be inactive, showed a similar reactivity to-
ward 2-cyclohexenone (1b) and the acyclic enone 1c. In this
respect, our findings do not support the criterion of the
cisoid conformation required from the Michael acceptor.
From our experimental results, therefore, it is possible to
predict that the efficiency of the catalytic process is strongly
dependent on the nature of the β-dicarbonyl compounds
and the metal ion to form a complex, which can be a dion-
ato complex I or some other undefined complex. According
to our observation, an important part of the mechanism of
this reaction could be that the proton released during the
formation of the dionato complex protonates the carbonyl
oxygen atom of the acceptor (in situ protonation) and pre-
vents the coordination of the oxygen atom to the metal cen-
ter. On the other hand, the extent of the protonation de-
pends on the nature of the counteranion in the Lewis acid
and the Michael donor used. In this respect, the metal salts
of strong protic acids having high negative standard en-
thalpy values, such as TfOH should have a more pro-
nounced in situ protonation effect and make them highly
Scheme 4.
stituted dihydrofurans is of practical importance. Indeed, it
is only recently that CAIRC has been proved as a synthetic
path to dihydrofurans using α-haloalkenones.
the above-mentioned and some other reports of the success-
[26]
Though
[27]
ful synthesis of dihydrofurans
have been available for
quite some time, the CAIRC reaction of β-dicarbonyl com-
pounds with α-halo-substituted Michael acceptors medi-
ated by Lewis acids has not hitherto been exploited.
Therefore, the above-mentioned metal salts together with
FeCl ·6H O were surveyed for the reactions of β-dicarbonyl
3
2
compounds with 2-bromo enones for the synthesis of
heterocycles through CAIRC reaction. Cu(OTf) , Sc(OTf) ,
2
3
In(OTf) , Zn(OTf) and FeCl ·6H O gave moderate yields
3
2
3
2
of 2,3-dihydrofuran derivatives and some selected examples,
which demonstrate the general feasibility of the present
method for the reaction of β-dicarbonyl compounds with
1d and 1e, are summarized in Scheme 5 and Table 3. Al-
III
though the strong tendency of Fe to form dionato com-
plexes to perform the conjugate addition is well
[21b,23]
known,
catalysis of CAIRC reactions by FeCl ·6H O
3 2
has not yet been explored. This catalytic transformation ap-
peared to be specific as β-keto esters and acyclic β-dike-
tones are the only reactive nucleophiles giving moderate
yields. Besides, the CAIRC transformation is not as efficient
as the corresponding conjugate-addition reaction, both in
reactivity and yields. This is because the bromide ion traps
the proton before it coordinates to the carbonyl oxygen
atom and then the metal enolate is protonated by HBr.
However, the present procedure is highly selective com-
pared with a base-mediated phase-transfer-catalyzed reac-
tion, which gives a single product. For example, when β-
[
18]
efficient catalysts for the formation of stable complexes.
Therefore, the “dual activation” of the reacting species
possibly determines the rate of addition (Scheme 4). In ad-
dition, a dionato complex I has a planar structure and is
stabilized by π-delocalization. Therefore, the power of π-
delocalization could affect the energy of the O–M+ bond
which is then responsible for the transfer of the enolate to
the acceptor. Thus, these factors may also well explain the
lesser reactivity of β-diesters in this catalytic process.
n
Finally, this work directed our next efforts to develop a
strategy for the synthesis of heterocycles through CAIRC
reaction using the same reaction conditions. During the last
decades, several methods have been developed for the syn-
thesis of dihydrofurans. However, the synthesis of polysub-
stituted dihydrofuran derivatives is much more difficult
than the synthesis of less substituted systems.[ Therefore,
25]
a mild and efficient method for the preparation of polysub- Scheme 5.
2010
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Heterocycles by Catalyzed Conjugate Addition using Michael Acceptors
Table 3. Solvent-free Lewis acid catalyzed CAIRC reaction of the β-dicarbonyl compounds 2a–c with Michael acceptors 1d and 1e.
FULL PAPER
[a] n.d.: not determined.
keto esters were treated with acyclic 2-haloalkenones such transfer-catalyzed CAIRC reaction route, in which the out-
as 1e in a base-mediated phase-transfer-catalyzed reaction, come of the reaction for the synthesis of rings is crucially
the cyclopropanes 8 are unavoidable byproducts along with dependent on the choice of the appropriate bases, phase-
the dihydrofurans 7.[
26a]
However, only dihydrofurans were transfer catalyst and solvent. We also believe that the pres-
isolated in Lewis acid catalyzed reactions (Scheme 6).
ent method offers considerable advantages in view of its
high efficiency, experimental simplicity, wide range of appli-
cability, catalysts stability and convenient workup pro-
cedure. The observed selectivity of the conjugate addition
and CAIRC reactions may also be of value in the synthesis
of polyfunctional molecules.
Scheme 6.
Experimental Section
General Methods: All H and 13C NMR spectra were recorded with
1
3
a JEOI JNM-EX 400 FT-NMR system using CDCl as a solvent
at room temperature. Chemical shifts are given in ppm and J values
in Hz. Analytical TLC was carried out on precoated (0.25 mm)
Merck silica gel F-254 plates. Flash chromatography was carried
out using granular silica (Si-60A° 35–70 µm). GLC analysis was
performed with a Varian 3300 chromatograph equipped with a split
injector, FID detector and a Varian 4400 integrator. IR spectra
were recorded with an FT-IR spectrometer and are reported as
wave numbers. GC-MS spectra were registered with a Hewlett
Packard 5890 series II CP Sil 5 CB column (25 m) followed by VG
Conclusion
We have presented a novel Lewis acid mediated pro-
cedure for the conjugate addition of β-dicarbonyl com-
pounds to enones as well as the CAIRC reaction of α-
bromo enones under mild conditions. The method expands
the applicability of conjugate-addition reactions in the pres-
ence of Lewis acids and offers a practical alternative to the
existing procedures. Furthermore, this protocol is also a Quattro mass spectrometer. Fison Prosoec-Q was used to obtain
complement and an alternative to the base-mediated phase- HREIMS data and the spectra were obtained at 250 °C and 70 eV.
Eur. J. Org. Chem. 2006, 2005–2013
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A. Mekonnen, R. Carlson
FULL PAPER
Melting points are uncorrected and are determined in open capil-
laries with a Büchi 535 apparatus. All reagents and solvents, except
H), 6.16–6.25 (m, 1 H), 7.45–7.58 (m, 1 H), 7.60–7.70 (m, 2 H),
7.95–8.10 (m, 2 H) ppm. C NMR: δ = 217.3, 203.0, 195.2
(–COPh), 165.5 (C), 134.3 (CH), 129.5 (CH), 129.0 (CH), 69.6
1
3
2
-bromocyclopentenone (1d) and 3-bromo-3-vinyl methyl ketone
1e), were obtained from commercial sources and used as received
without further purification. The compounds 1d and 1e were pre-
(
(CH), 43.0 (CH
ppm. HRMS: calcd. for C15
2
), 38.6 (CH
2
), 37.3 (CH), 38.1 (CH
244.10994; found 244.10988.
-Hydroxy-6-(3-oxocyclopentyl)cyclohex-2-enone (3k): Yield 0.06–
.14 g, 31–72%, brown oil, R = 0.53 (EtOAc/pentane, 3:7). IR
2 3
), 27.4 (CH )
16 3
H O
[29]
pared according to a literature procedure. All compounds were
identified by their DEPT, 1H, and C NMR and HRMS data.
Relevant references are given for known compounds.
2
0
13
f
(
1
6
neat, NaCl plates): ν˜ max = 3084, 2940, 2248, 1738, 1706, 1402,
–
1 1
381, 1181 cm . H NMR: δ = 1.52–2.20 (m, 4 H), 2.30–2.65 (m,
H), 2.75–3.05 (m, 2 H), 6.20 (s, 1 H), 7.72–7.75 (m, CH=C–)
General Experimental Procedure for the Synthesis of Compounds 3,
4
and 5: A mixture of the enone 1a, 1b or 1c (1.0 mmol), a Lewis
1
3
ppm. C NMR: δ = 210.4, 204.3, 165.5 (CH=C–), 134.6 (C), 47.5
CH), 39.6 (CH), 39.0 (CH ), 34.2 (CH ), 34.0 (CH ), 29.3 (CH ),
) ppm. HRMS: calcd. for C11 194.0943; found
acid (0.1 mmol) and a β-dicarbonyl compound 2 (2.0 mmol) was
allowed to stand at room temperature until the reaction was com-
pleted. Then the reaction mixture was diluted with a suitable sol-
(
2
1
2
2
2
2
8.7 (CH
94.0939.
2
14 3
H O
2 2 2
vent (usually Et O/CH Cl ), and the desired products were ob-
tained in high chemical purity after a simple filtration through a
short pad of silica gel. In some cases, the crude mixtures were di-
rectly chromatographed on silica gel using appropriate solvents
3-Acetyl-3-(3-oxocyclopentyl)dihydrofuran-2-one (3l): Yield 0.11–
0.18 g, 54–87%, yellow oil, R = 0.56 (EtOAc/pentane, 3:7). IR
f
(neat, NaCl plates): ν
˜
max
= 2966, 2919, 1743, 1712, 1405, 1376,
(
solvents used to determine R
f
values).
1173, 1027 cm–1
.
1
H NMR: δ = 1.85–2.10 (m, 2 H), 2.10–2.25 (m,
2
3
H), 2.30–2.45 (m, 1 H), 2.34 (s, 3 H), 2.82 (t, J = 10.0 Hz, 2 H),
Methyl 2,3Ј-Dioxo-1,1Ј-bi(cyclopentyl)-1-carboxylate (3f): Yield
1
3
.07 (d, J = 6.4 Hz, 2 H), 4.15 (t, J = 8.0 Hz, 2 H) ppm. C NMR:
O–), 64.0 (C), 40.1 (CH), 39.9
), 25.3 (CH ), 24.4 (CH ) ppm.
210.0892; found 210.0895.
0
3
1
1
2
.15–0.20 g, 67–90%, white crystals, R
f
= 0.42 (EtOAc/pentane,
δ = 216.5, 202.0, 174.8, 66.2 (CH
(CH ), 38.2 (CH ), 25.6 (CH
HRMS: calcd. for C11
2
:7); m.p. 60–61 °C. IR (neat, NaCl plates): ν˜ max = 3053, 2858,
–1
1
2
2
2
3
2
740, 1695, 1421, 1264 cm . H NMR: δ = 1.60–1.78 (m, 2 H),
.90–2.05 (m, 2 H), 2.10–2.23 (m, 2 H), 2.32–2.39 (m, 2 H), 2.44–
14 4
H O
.55 (m, 4 H), 2.82–2.9 (m, 1 H), 3.72 (d, J = 6.8 Hz, 2 H), 3.74 Typical Experimental Procedure for the Synthesis of Compounds 6
(
(
(
s, 3 H) ppm. 13C NMR: δ = 216.5 (–CO), 214.2 (–CO), 172.3
and 7: A mixture of the 2-bromo enone 1d or 1e (1.0 mmol), a
), 41.0 (CH), 39.5 Lewis acid (0.1 mmol) and a β-dicarbonyl compound 2 (2.0 mmol)
–COO–), 61.8 (C), 52.7 (–OCH
CH ), 31.0 (CH ), 30.6 (CH ), 24.6 (CH
224.1049; found 224.1049.
3
), 41.9 (CH
2
2
2
2
2
), 19.8 (CH
2
) ppm.
was kept at room temperature without stirring for several hours to
ensure complete conversion. The reaction mixture was diluted with
16 4
HRMS: calcd. for C12H O
Et
raphy (Et
Methyl 2-Methyl-6-oxo-4,5,6,6a-tetrahydro-3aH-cyclopenta[b]furan-
3-carboxylate (6a): Yield 0.06–0.15 g, 29–77%, yellow oil; R = 0.34
2
O, concentrated and purified using silica gel column chromatog-
Ethyl 2-Oxo-1-(3-oxocyclopentyl)cyclohexane-1-carboxylate (3g):
Yield 0.01–0.21 g, 13–84%, colorless oil, R = 0.37 (EtOAc/pentane,
:7). IR (neat, NaCl plates): ν˜ max = 2940, 2866, 1740, 1710, 1447,
240, 1206 cm . H NMR: δ = 1.26 and 1.30 (t, J = 7 Hz, 3 H),
.51–1.72 (m, 2 H), 1.80–2.08 (m, 4 H), 2.05–2.25 (m, 2 H), 2.30–
.42 (m, 4 H), 2.43–2.58 (m, 2 H), 2.65–2.80 (m, 1 H), 4.20–4.34
2
O/pentane, 30:70) to obtain the desired adducts.
f
3
1
1
2
–1 1
f
(
1
Et
732, 1585, 1321, 1193 cm . H NMR: δ = 2.17 (s, 3 H), 2.18–2.35
(m, 2 H), 2.28–2.41 (m, 2 H), 3.96 (s, 3 H), 4.23 (t, J = 8.0 Hz, 1
2
O/pentane, 3:7). IR (neat, NaCl plates): ν˜ max = 3010, 2992,
–
1 1
m, 2 H) ppm. 1 C NMR: δ = 217.7, 207.5, 171.5, 66.0 (–OCH
3
(
2
),
), 34.6
) ppm.
1
3
H), 4.84 (d, J = 9.6 Hz, 1 H) ppm. C NMR: δ = 15.4 (CH
CH ), 34.5 (CH ), 44.3 (CH), 52.4 (CH ), 84.0 (CH), 105.5 (C),
25.6 (C), 165, 202 ppm. HRMS: calcd. for C10 196.0733;
3
), 25.6
6
2.5 (C), 61.8 (CH
CH ), 27.4 (CH ), 24.3 (CH
HRMS: calcd. for C14 252.1362; found 252.1358.
2
), 42.3 (CH
2
), 41.2 (CH), 38.5 (CH
2
(
2
2
3
(
2
2
2
), 22.5 (CH
2
), 14.3 (CH
3
1
12 4
H O
20 4
H O
found 196.0735. The signal (δ = 4.23 ppm) of the proton, which
coupled to one proton along the ring junction and to two geminal
protons on the ring, appeared as a triplet instead of a multiplet
2
-Acetyl-2-(3-oxocyclopentyl)cyclohexanone (3h): Yiels trace–0.13 g,
trace–58%, colorless oil, R = 0.40 (EtOAc/pentane, 3:7). IR (neat,
NaCl plates): ν˜ max = 2956, 1742, 1404, 1265, 1230 cm . H NMR:
δ = 1.52–1.74 (m, 2 H), 1.78–1.92 (m, 4 H), 1.98–2.14 (m, 2 H),
2
2
f
–1 1
(
ddd). The same was true for compounds 6b and 6c. This is because
of the effect of dihedral angles and similar values of the coupling
constants among the coupled protons. The same phenomenon was
.16 and 2.17 (s, 3 H), 2.20–2.44 (m, 4 H), 2.46–2.54 (dt, 1 H),
.86–2.98 (m, 2 H) ppm. 13C NMR: δ = 217.6, 214.5, 203.6, 67.6
[30]
also observed for the cyclopropanated adducts.
(C), 42.3 (CH
2
), 40.9 (CH), 40.0 (CH
), 26.2 (CH ), 24.5 (CH ), 22.2 (CH
222.1256; found 222.1254.
2
), 39.7 (CH
2 2
), 38.6 (CH ),
Ethyl 2-Methyl-6-oxo-4,5,6,6a-tetrahydro-3aH-cyclopenta[b]furan-
3
0.4 (CH
3
2
2
2
) ppm. HRMS:
3
-carboxylate (6b): Yield 0.03–0.14 g, 15–68%, yellow oil; R
f
=0.34
O/pentane, 3:7). H NMR: δ = 1.24 (t, J = 7.0 Hz, 3 H), 2.15
s, 3 H), 2.10–2.36 (m, 2 H), 2.34–2.51 (m, 2 H), 4.17 (q, J = 7.0 Hz,
18 3
calcd. for C13H O
1
(Et
2
2
1
-(3-Oxocyclopentyl)cyclohexane-1,3-dione (3i): Yield 0.02–0.14 g,
(
2–72%, yellow crystals, R = 0.51 (EtOAc/pentane, 3:7). IR (neat,
f
13
2
H), 4.30 (t, J = 7.6 Hz, 1 H), 4.80 (d, J = 9.6 Hz, 1 H) ppm.
NMR: δ = 15.0 (CH ), 20.12 (CH ), 25.4 (CH ), 34.0 (CH ), 44.8
CH), 53.0 (CH ), 84.6 (CH), 104.7 (C), 125.0 (C), 166.5, 201.5
ppm. HRMS: calcd. for C11 210.0888; found 210.0892.
-Acetyl-2-methyl-3a,4,5,6a-tetrahydro-cyclopenta[b]furan-6-one
6c): Yield 0.03–0.16 g, 18–89%, light yellow oil; R = 0.37 (Et O/
pentane, 3:7). IR (neat, NaCl plates): ν˜ max = 2998, 1736, 1645,
C
–1
NaCl plates): ν˜ max = 2960, 1732, 1601, 1386,1328 cm . M.p. 136–
3
3
2
2
1
136.9 °C. H NMR: δ = 1.70–1.95 (m, 2 H), 2.05–2.30 (m, 2 H),
2.32–2.42 (m, 2 H), 2.46 (t, J = 6.4 Hz, 2 H), 2.55–2.80 (m, 4 H),
2
.90–2.98 (m, 1 H), 3.63 (d, J = 7.6 Hz, 2 H) ppm. 13C NMR: δ =
2
(
2
14 4
H O
3
(
04.0 (CO), 71.8 (CH), 42.8 (CH
2
), 40.6 (CH), 39.0 (CH
), 21.0 (CH ) ppm. HRMS: calcd. for
14 3
O 194.0943; found 194.0944.
2
), 38.4
f
2
(CH
2
), 33.7 (CH
2
), 27.3 (CH
2
2
C
11
H
–
1 1
1335, 1261, 1167 cm . H NMR: δ = 2.15–2.40 (m, 2 H), 2.30 (s,
2
-(3-Oxocyclopentyl)-1-phenylbutane-1,3-dione (3j): Yield 0.12–
3 H), 2.38 (s, 3 H) 2.48–2.57 (m, 2 H), 4.16 (t, J = 8.0 Hz, 1 H),
1
3
0
.22 g, 49–91%, brown oil, R = 0.29 (EtOAc/pentane, 3:7). IR
f
4.68 (d, J = 9.6 Hz, 1 H) ppm. C NMR: δ = 16.7 (CH
), 30.0 (CH ), 36.3 (CH ), 44.4 (CH), 83.5 (CH), 116.2 (C),
NMR: δ = 2.15 and 2.18 (s, 3 H), 2.20–2.50 (m, 2 H), 2.72 (t, J = 128.0 (C), 194.8 (C=O), 214.3 (C=O) ppm. HRMS: calcd. for
3
), 26.2
–
1 1
(neat, NaCl plates): ν˜ max = 2964, 1740, 1675, 1359, 1183 cm . H (CH
2
3
2
4.8 Hz, 2 H), 3.15–3.24 (m, 1 H), 4.44 (dd, J = 6.0 and 4.0 Hz, 2
10 12 3
C H O 180.0783; found 180.0786.
2012
www.eurjoc.org
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2006, 2005–2013

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Received: November 25, 2005
Published Online: February 9, 2006
Eur. J. Org. Chem. 2006, 2005–2013
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
2013