Microwave-induced synthesis and regio- and stereoselective epoxidation of 3-styrylchromones

Article abstract of DOI:10.1002/ejoc.200701081

The microwave-assisted solvent-free synthesis of (E)-3-styrylchromones from 3-formylchromones and phenylmalonic acid on sodium acetate support has been developed; the method affords the styryl derivatives in moderate to good yields and with complete diastereoselectivity. Protocols for the highly regioselective epoxidation of (E)- and (Z)-3-styrylchromones have been elaborated. Treatment of the alkenes with dimethyldioxirane led to the exclusive formation of 3-(3-aryloxiran-2-yl)chromones with complete diastereoselectivity, whereas treatment with hydrogen peroxide under alkaline conditions afforded the corresponding 2,3-epoxy-3-styrylchromanones as the only products. Epoxidation performed in the presence of chiral, nonracemic cinchona-alkaloid-based quaternary ammonium salts allowed the synthesis of enantiomerically enriched 2,3-epoxy-3-styrylchromanones, but with only moderate ee values. Wiley-VCH Verlag GmbH & Co. KGaA, 2008.

Full text of DOI:10.1002/ejoc.200701081

FULL PAPER
DOI: 10.1002/ejoc.200701081
Microwave-Induced Synthesis and Regio- and Stereoselective Epoxidation of
3-Styrylchromones
Tamás Patonay,*[a] Attila Kiss-Szikszai,[b] Vera M. L. Silva,[c] Artur M. S. Silva,[c]
[c]
[c]
[d]
˝
Diana C. G. A. Pinto, José A. S. Cavaleiro, and József Jeko
Dedicated to Professor Csaba Szántay on the occasion of his 80th birthday
Keywords: Solvent-free reaction / Microwave-assisted synthesis / Enantioselective epoxidation / O heterocycles
The microwave-assisted solvent-free synthesis of (E)-3-sty-
rylchromones from 3-formylchromones and phenylmalonic
acid on sodium acetate support has been developed; the
method affords the styryl derivatives in moderate to good
yields and with complete diastereoselectivity. Protocols for
the highly regioselective epoxidation of (E)- and (Z)-3-styryl-
chromones have been elaborated. Treatment of the alkenes
with dimethyldioxirane led to the exclusive formation of 3-
(3-aryloxiran-2-yl)chromones with complete diastereoselec-
tivity, whereas treatment with hydrogen peroxide under al-
kaline conditions afforded the corresponding 2,3-epoxy-3-
styrylchromanones as the only products. Epoxidation per-
formed in the presence of chiral, nonracemic cinchona-alka-
loid-based quaternary ammonium salts allowed the synthesis
of
enantiomerically
enriched
2,3-epoxy-3-styrylchro-
manones, but with only moderate ee values.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2008)
Introduction
alkylstyryl)chromones.[5] Another possibility is the discon-
nection of the C-α=C-β double bond; one possible synthetic
path could be the Wittig reaction. (E)-2-Methyl-3-(3Ј,5Ј-di-
hydroxystyryl)chromone has been prepared from the appro-
priate benzaldehyde and a phosphonium salt generated
from 3-(bromomethyl)chromone.[6] The main drawback of
this approach is the troublesome selective monobromin-
ation of 3-methylchromone and the competitive nuclear
bromination in the presence of hydroxy/alkoxy groups on
the A-ring. The alternative Wittig route utilizes 3-formyl-
chromones and benzylidenephosphoranes. These reactions
give mixtures of (Z)- and (E)-3-styrylchromones, which are
separable by chromatography on silica.[7] The major prod-
uct in each case is the (Z) diastereomer, and this protocol
provides the best method to prepare this isomer. The other
synthetic route based on C-α=C-β disconnection is the
Knoevenagel-type condensation of 3-formylchromones
with activated methyl or methylene groups.[8] Recently, we
have published a new and efficient method of this type.
Treatment of 3-formylchromones with phenylacetic acids in
pyridine solution and in the presence of potassium tert-
butoxide either under conventional heating conditions or
under microwave (MW) irradiation conditions resulted in a
wide range of (E)-3-styrylchromones.[9] In this contribution
we wish to disclose our newly developed solvent-free MW
protocol using phenylmalonic acid as the source of the
nucleophile. This method offers rapid and easy access to
the target styryl derivatives.
Chromones with styryl groups at their 2- or 3-positions
represent a small and rare class of naturally occurring chro-
mones. Some of these natural products and their synthetic
analogues show marked biological activities.[1] A series of
radioiodinated 2-styrylchromones as promising β-amyloidal
imaging agents has recently been reported.[2] Syntheses and
transformations including Diels–Alder reactions and 1,3-di-
polar cycloadditions have also been reviewed.[3]
In comparison with the extensively studied methods for
the synthesis of 2-styrylchromones, far fewer procedures
have been developed for 3-styrylchromones. Heck reactions
of 3-bromochromones offer an obvious approach, but up
to now only one paper has been published, presenting the
synthesis of the unsubstituted parent compound.[4] Two-
step oxidative cyclizations of (E,E)-5-aryl-1-(2-hydroxy-
phenyl)-2,4-pentadien-1-ones give the desired backbone,
but this method is limited to the preparation of 3-(α-
[a] Department of Organic Chemistry, University of Debrecen,
4010 Debrecen, Hungary
Fax: +36-52-453-836
E-mail: tpatonay@puma.unideb.hu
[b] Carbohydrate Research Group, Hungarian Academy of Sci-
ences – University of Debrecen,
4010 Debrecen, Hungary
[c] Department of Chemistry, University of Aveiro,
3810-193 Aveiro, Portugal
[d] Department of Chemistry, College of Nyíregyháza,
4440 Nyíregyháza, Hungary
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1937

T. Patonay et al.
FULL PAPER
In continuation of our work on epoxidations of various
oxygen heterocycles and their precursors with dioxiranes
and other oxygen sources and on the use of (salen)manga-
nese(III) complex (Jacobsen’s complex) as a catalyst in these
reactions,[10] we also started detailed studies on the oxi-
dation of styrylchromones. Results on the oxidation of 2-
styrylchromones with dimethyldioxirane (DMD) and also
with hydrogen peroxide and iodosobenzene in the presence
of Jacobsen’s catalyst have recently been reported. Because
of the low reactivities of these substrates and the highly
unstable characters of the epoxides formed, oxidations
should be quenched at low levels of conversion; thus, these
transformations have only limited synthetic value.[11] In
contrast, we have found that the epoxidation of 3-styryl-
chromones can be performed in a regio- and stereoselective
manner and in good yields through the use of DMD or
alkaline hydrogen peroxide (Weitz–Scheffer oxidation).
Moreover, moderate enantioselectivities were observed
when Weitz–Scheffer oxidation was conducted in the pres-
ence of cinchona-based quaternary ammonium salts as
phase-transfer catalysts (Wynberg oxidation). The results of
these experiments are also presented in this contribution.
Scheme 1.
2 equiv. of phenylmalonic acid performed on silica support
could be useful. It was also found that two additional
batches of phenylmalonic acid up to a total of 4 equiv.
should be added to achieve acceptable (80–90%) levels of
conversion and moderate (18–46%) yields. However, these
results were not reproducible in a professional single-mode
MW laboratory instrument, giving a further example of the
drawbacks of the domestic apparatus in synthetic organic
chemistry.[15] Of various supports (silica, sodium sulfate, so-
dium carbonate, sodium acetate, alumina, Montmorillon-
ite K-10) tested in the single-mode MW apparatus, sodium
acetate proved to be optimal. MW irradiation (100 °C inte-
rior temperature for 6 min) gave the desired 3-styrylchro-
mones 3a–g in moderate to good (47–61%) yields and with
complete (E) diastereoselectivities, no (Z) diastereomers be-
ing detectable or isolable (Scheme 1). The simplicity of the
aqueous workup and the fact that only very limited
amounts of organic solvent were needed to provide analyti-
cally pure products (E)-3a–g make this procedure an ef-
ficient and “green” protocol for the synthesis of 3-styryl-
chromones.
Results and Discussion
Synthesis of (E)-Styrylchromones
In continuation of our work on the synthesis of (Z)-3-
styrylchromones through the reactions of 3-formylchro-
mones with phenylacetic acids in pyridine solution and in
the presence of potassium tert-butoxide under microwave
(MW) irradiation conditions[9] we have performed experi-
ments using phenylmalonic acid as the precursor of the sty-
ryl unit. The choice of the reagent was based on the as-
sumption that the incorporation of the second carboxyl
group should enhance the C–H acidity and, therefore, pro-
mote the Knoevenagel condensation. The starting materi-
als, 3-formylchromones 2 (Scheme 1), were prepared by
Vilsmeier–Haack treatment of 2Ј-hydroxyacetophenones 1
according to literature procedures.[12,13] In the cases of ace-
tophenones 1g and 1h, which contain strongly electron-do-
Dimethyldioxirane Oxidation of 3-Styrylchromones
Treatment of dichloromethane (DCM) solutions of the
nating methoxy or benzyloxy groups at their 4Ј-positions, prepared styrylchromones (E)-3a–f with 4 equiv. of di-
the reactions took place with very low yields (7% and 26%, methyldioxirane (DMD) in acetone[16] resulted in fast reac-
respectively). Similarly poor yields for chromone 2g have tions and afforded good to excellent (55–95%) yields of sin-
been reported previously.[13,14] Product 2g was obtained in gle products that were identified as trans-3-(3-phenyloxiran-
better yield (24%) via the boron trifluoride complex of ace- 2-yl)chromones trans-4a–f (Scheme 2). Epoxidation took
tophenone 1g by the modified protocol reported by Zúñiga place with complete regio- and diastereoselectivity in all
and co-workers.[14] This approach was also tested for the cases. The appearance of the α-H and β-H methine proton
development of an improved synthesis of benzyloxy deriva- signals at δ = 3.82–3.84 ppm and δ = 4.13–4.16 ppm,
1
tive 2h, but it failed due to the debenzylation of 4Ј-ben- respectively, in the H NMR spectra, in addition to the ap-
zyloxy-2Ј-hydroxyacetophenone (1h) in the attempted syn- pearance of the C-α and C-β methine carbon atom signals
thesis of the borane intermediate.
at δ = 55.9–56.2 ppm and δ = 54.0–54.6 ppm, respectively,
To develop an environmentally benign approach to the in the 13C NMR spectra, unequivocally confirmed that
MW-induced condensation of formyl derivatives 2 with epoxidation had occurred at the styryl double bonds. The
1
phenylmalonic acid, we wished to investigate solvent-free unchanged 2-H singlets in the H NMR spectra, the C-2
transformations in the presence of various supports. Our and C-3 signals in the 13C NMR spectra and the C=O
first experiments were conducted in a simple domestic MW stretching in the IR spectra clearly show that the C-2=C-3
oven and indicated that reactions between aldehyde 2a and double bonds remained intact.
1938
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Microwave-Induced Synthesis and Selective Epoxidation of 3-Styrylchromones
tivity of the chromone double bond toward DMD had pre-
viously been observed in the cases of the parent compound
and of some derivatives substituted in their A-rings. In the
oxidation of these substrates, very large amounts (12–
25 equiv.) of DMD were required to obtain moderate (43–
51%) levels of conversion in the epoxidation reactions.[20]
Isoflavones (3-phenylchromones) showed somewhat higher
reactivities but still needed large excesses (11–16 equiv.) of
DMD for the completion of their epoxidations.[21] In con-
trast, a styryl group connected to the α-position of an α,β-
enone system has normal or slightly increased electron den-
sity and is therefore sensitive to the attack of the electro-
philic DMD. Similar discrimination has been reported in
the case of methyl 2,6-octadienoate derivatives, in which the
dioxirane exclusively attacked the electron-rich 6,7-double
bond while the electron-poor 2,3-double bond remained in-
tact.[22]
We have pointed out that the combination of DMD and
Jacobsen’s (salen)MnIII complex represents a new, syntheti-
cally valuable enantioselective oxidizing system that works
Scheme 2.
Epoxidation of the (Z) diastereomers gave similar results. under mild and neutral conditions.[10e,10f,10h,23] This combi-
DMD treatment of substrates (Z)-3a, (Z)-3b and (Z)-3i–k nation allowed us to synthesize enantiomerically enriched
led to the formation of the cis-3-(3-phenyloxiran-2-yl)chro- isoflavones in moderate (22–39%) yields, with the enantio-
mones cis-4a, cis-4b and cis-4i–k in excellent (80–96%) meric excesses varying over a wide range (21–90%) de-
yields. Again, the epoxidations took place with complete pending on the substitution patterns. It is noteworthy that
regio- and diastereoselectivity. The relative configurations large amounts of DMD (6–10 equiv.) were again needed to
of the 2,3-disubstituted epoxides 4 were assigned on the ba- achieve these moderate yields. We also tested the DMD/
3
sis of their J2-H,3-H coupling constants: values of 1.5– (salen)MnIII system in the epoxidation of (E)-3-styrylchro-
2.1 Hz were measured for the trans isomers, whereas values mone [(E)-3a]. Unfortunately, the regioselectivity that we
of 3.9–4.3 Hz were found for the cis isomers.
had observed in the reaction of DMD in the absence of
Comparison of the H NMR chemical shifts of the α- MnIII complex was completely lost, and only a mixture of
H and β-H methine proton signals revealed a difference of the monoepoxides trans-4a and (E)-5a and the two dia-
diagnostic value. While the α-H and β-H signals in the spec- stereomers of diepoxide 6a was detected by 1H NMR spec-
tra of the trans isomers appeared at δ = 3.82–3.84 ppm and troscopy. The ratio of the products depended on the
4.13–4.16 ppm, the corresponding signals for the cis iso- amounts of the oxygen source used (Scheme 3). The at-
mers showed marked downfield shifts: the α-H and β-H sig- tempted separation of the epoxides by column chromatog-
nals for these diastereomers were moved to δ = 4.40– raphy on silica failed, due to the complexities of the mix-
4.47 ppm (∆δ ≈ +0.6 ppm) and 4.46–4.57 ppm (∆δ ≈ tures and the labile characters of the diepoxides. This loss
+0.35 ppm), respectively. This phenomenon could be inter- of regioselectivity can be attributed to the enhanced reactiv-
preted in terms of the different conformations. In the domi- ity of the actual oxidizing agent [i.e., the (oxido)MnV com-
nant conformer of the cis isomers, both the α-H and the β- plex formed from the original MnIII catalyst].
H hydrogen atoms are located in proximity to the carbonyl
1
function of the chromone skeleton; thus, the anisotropic
shift of the carbonyl group results in a downfield shift. In
the trans diastereomers both hydrogen atoms are far from
the carbonyl function.
The complete diastereoselectivity is in accordance with
previously made observations during the DMD epoxida-
tions. The (E) Ǟ trans vs. (Z) Ǟ cis selectivity could be
interpreted on the basis of the concerted “butterfly” transi-
tion state of the dioxirane oxidations.[17,18] The exclusive at-
tack of DMD at the styryl double bond can be explained in
terms of the highly electrophilic character of the oxidizing
agent.[18,19] Because of the electron-withdrawing effect of
the C-4 carbonyl group, the C-2=C-3 double bond of the
endocyclic α,β-enone system is electron-deficient; thus, it is
less reactive toward electrophilic oxidants and tends to seek
for nucleophilic oxidizing agents instead. Diminished reac- Scheme 3.
Eur. J. Org. Chem. 2008, 1937–1946
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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T. Patonay et al.
FULL PAPER
Weitz–Scheffer Oxidation of 3-Styrylchromones
ity to the 2-H atom in the (Z) compounds. The C-2, C-3
and C-4 atoms showed the expected chemical shifts (C-2
signal at δ = 61.1–62.4 ppm, C-3 signal at δ = 82.4–
83.9 ppm and C-4 signal at δ = 187.1–188.7 ppm), charac-
teristic of substituted chromanone rings. The C=O stretch-
ing in their IR spectra (1670–1688 cm–1) provided further
evidence of the presence of the chromanone units. The sty-
ryl double bonds and their relative configurations remained
unchanged in all cases, as was confirmed by their chemical
To test the assumed reactivity of the 2,3-double bond of
the chromone ring toward nucleophilic oxidizing agents, we
initiated studies on the reactions of (E)- and (Z)-3-styryl-
chromones with alkaline hydrogen peroxide. Only a very
few results on the Weitz–Scheffer epoxidation of chromones
and isoflavones have so far been reported. In an early paper,
the transformation of 2-methylisoflavone into its epoxide
was reported as the only example.[24] Later, various 2-un-
substituted isoflavones were epoxidized by this methodol-
ogy.[10g,25] The first synthesis of chromone epoxide under
alkaline conditions by treatment either with hydrogen per-
oxide[26] or with cyclohexylidenebis(hydroperoxide)[27] was
reported very recently. Bernini and co-workers[28] found
that the Weitz–Scheffer epoxidation of chromones and iso-
flavones took place more rapidly in ionic liquid than in con-
ventional solvents.
Treatment of 3-stryrylchromones (E)-3a–f and (Z)-
3a,b,i–k with hydrogen peroxide and sodium hydroxide in
various solvents (acetone, methanol, 1,4-dioxane and
[bmim]PF4 ionic liquid) afforded the expected 2,3-epoxy-3-
styrylchromones (E)-5a–f and (Z)-5a,b,j,k, the best isolated
yields [27–63% for the (E) and 69–82% for the (Z) deriva-
tives] being obtained by using acetone or 1,4-dioxane
(Scheme 4). Surprisingly, substrate (Z)-3i failed to give any
oxidation product, with only the unreacted starting material
being recoverable. The epoxidation again took place with
complete regioselectivity, with only 2,3-epoxides being iso-
lable or detectable. We were thus able to develop methods
for the synthesis of either of the monoepoxides of the 3-
styrylchromones simply by changing the electrophilicity/nu-
cleophilicity of the oxidizing reagent. The structures of the
obtained epoxides (E)-5a–f and (Z)-5a,b,j,k were confirmed
by the marked upfield shifts of the 2-H signals to δ = 5.51–
5.54 ppm in the cases of epoxides (E)-5a–f and to δ = 5.21–
5.31 ppm in the cases of epoxides (Z)-5a,b,j,k. The different
shifts can be attributed to the anisotropy effects of the sty-
ryl double bond and of the phenyl ring, which is in proxim-
shifts in the H and 13C NMR spectra and their Jα-H,β-H
coupling constants. The weak cross-peaks in the COSY
spectra between the signals of β-H and 2Ј,6Ј-H of derivative
(E)-5a and of α-H and 2-H of derivative (Z)-5a gave further
support for the stereochemistry. The complete assignment
1
3
1
of the H and 13C NMR signals of isomers (E)- and (Z)-5a
was carried out on the basis of their COSY and HET-
CORR spectra.
To make the assignment of the signals in the 13C NMR
spectra unambiguous we used the so-called J-echo (J-MOD,
J-modulated spin-echo) technique in all cases. J-echo is a
1D method used for multiplicity editing. Through a judi-
cious choice of delay periods in the spin-echo (set by the
coupling constant), the experiment can be tuned to produce
spectra in which different multiplicities produce differing re-
sponses. A typical experiment would provide spectra in
which the quaternary and methylene signals would have the
opposite phase to the methine and methyl resonances. How-
ever, in the 13C NMR spectra of epoxides (E)-5a–f and (Z)-
5a,b,j,k we observed an anomalous behaviour of the C-2
atoms, as they changed their phases and looked like quater-
nary or methylene signals. A probable explanation for this
unique characteristic could be based on the difference in
1
the JC,H coupling constant of C-2 in the epoxide ring and
the average coupling constant (140 Hz) used in the J-echo
experiment to set the measuring parameters. The smallest
1
rings have much larger JC,H values (e.g. J = 160 Hz in cy-
clopropane[29]); thus, the C-2 signal has the opposite phase
at the end of the experiment and appears as a methylene
carbon atom.
Wynberg Oxidation of 3-Styrylchromones
One of the best enantioselective epoxidation methods for
electron-poor alkenes such as α,β-enones and -enoates uti-
lizes hydrogen peroxide or other organic peroxides in alka-
line media and in the presence of chiral, nonracemic quater-
nary ammonium salts.[30] This methodology was invented
and developed by Wynberg and co-workers,[31] who used
ammonium salts derived from the cinchona alkaloids qui-
nine and quinidine as phase-transfer catalysts (PTCs). Cin-
choninium and cinchonidinium salts have also been found
to be effective, although the details on the optimum condi-
tions (substituents in the catalyst, solvent or base) are some-
what controversial.[32] Since we are strongly interested in the
development of enantioselective epoxidation methods for
oxygen-containing heterocycles, studies were commenced to
evaluate the Wynberg oxidation in the 3-styrylchromone
series.
Scheme 4.
1940
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Eur. J. Org. Chem. 2008, 1937–1946

Microwave-Induced Synthesis and Selective Epoxidation of 3-Styrylchromones
We performed our experiments with PTCs Cat 1–Cat 4 that Wynberg oxidation works well only in the series of acy-
prepared from cinchonine and quinidine by standard meth- clic (E)-enones. At the same time, there is no effective
ods using either benzyl bromides with strongly electron- metal-free method for the enantioselective epoxidation of
withdrawing groups (EWGs) in their 4-positions or 1-naph- the (Z) diastereomers or their endocyclic analogues yet.
thylmethyl chloride. The alkylating agents were chosen on
the basis of the results published by Arai and co-
workers;[32a,32b] the former family of catalysts had been
found to be useful in the epoxidation of chalcones, whereas
the latter was the PTC of choice in the case of 2-methyl-
1,4-naphthoquinone (Scheme 5).
Conclusion
Microwave-induced, solvent-free Knoevenagel condensa-
tion of phenylmalonic acid and various 3-formylchromones
on sodium acetate support was found to be a convenient
and environmentally benign method to produce (E)-3-sty-
rylchromones in moderate to good yields and with complete
diastereoselectivity.
Oxidation of 3-styrylchromones by DMD or hydrogen
peroxide in alkaline medium were demonstrated to take
place with complete regioselectivity; the former oxidant
resulted in 3-(3-aryloxiran-2-yl)chromones exclusively,
whereas the latter reagent led to the formation of 2,3-epoxy-
3-styrylchromones as sole products. This selectivity could
be interpreted in terms of the different electron density of
the double bonds. In accordance with the previously pos-
tulated transition state of the dioxirane oxidations, the for-
mation of 3-(3-aryloxiran-2-yl)chromones took place with
complete diastereoselectivity, and the relative configuration
was retained. Weitz–Scheffer oxidation in the presence of
cinchona-based quaternary ammonium salts as phase-
transfer catalysts provided the expected epoxides in poor
enantiomeric excesses; this finding gives a further proof that
this asymmetric oxidation works successfully only in the
case of acyclic 2-alken-1-ones.
Scheme 5.
In the epoxidation of parent compound (E)-3a, two frac-
tions of product (E)-5a were isolated. The first one precipi-
tated directly from the reaction mixture, while the second
was obtained by treatment of the mother liquor with water.
The fractions were analyzed separately. Both were identified
1
as pure epoxide (E)-5a by H NMR spectroscopy, but their
optical purities differed significantly. The first precipitate
(Fraction 1) in all cases proved to be nearly racemic, show-
ing only a marginal ee value, if any, whereas a moderate ee
value was measured in most cases for the precipitate ob-
tained from the mother liquor (Fraction 2) (Table 1). The
best ee value was achieved with catalyst Cat 1, in which the
strongly electron-withdrawing nitro group was attached at
the 4-position of the benzyl group. This seems to support
the observation of Arai and co-workers[32a,32b] on the bene-
ficial effects of these types of substituents, although they
found the bromo substituent to be superior to the nitro
group. In contrast with their results, the incorporation of
the bulkier naphthyl group did not improve the enantio-
selectivity.
Experimental Section
General: Melting points: Boetius hot-stage, uncorrected values. IR:
Perkin–Elmer 16 PC FT-IR; KBr pellets unless otherwise stated.
NMR: Bruker AM 360 (360 MHz for 1H; 90 MHz for 13C). Re-
corded in CDCl3 solution unless otherwise stated. Chemical shifts
are given in δ relative to an internal standard TMS (δ = 0 ppm) or
1
to the residual CHCl3 (δ = 7.26 ppm for H and δ = 77.0 ppm for
13C). 13C NMR assignments were supported by J-echo technique.
MS: VG Trio-2 (EI, 70 eV). Optical rotations: Perkin–Elmer 341 (l
= 1 dm), at 20 °C. Enantiomeric excesses (ee) were determined with
a Jasco HPLC instrument (PU 980 solvent delivery system and
pressure moderator, MD 910 diode array detector), Chiralcel OD
column (hexane/propan-2-ol = 95:5, v = 1 mLmin–1). Elemental
analysis: Carlo Erba. Microwave-induced syntheses: CEM Ex-
plorer. Thin-layer chromatography (TLC): Kieselgel 60 F254
(Merck) sheets, column chromatography: Kieselgel 60. Styrylchro-
mones (Z)-3a,b,i–k[7] and DMD solution in acetone[16] were pre-
pared according to literature procedures. MgSO4 was used as dry-
ing agent.
Table 1. Results for the enantioselective epoxidation of (E)-3-styryl-
chromone [(E)-3a] in the presence of quaternary cinchona-based
catalysts.
Cat
Fraction 1
Fraction 2
Weighted
Yield (%)
ee (%)
Yield (%)
ee (%)
ee (%)[a]
1
2
3
4
33
20
37
31
0.6
0.9
0.9
0.6
31
32
26
42
46
25
33
27
23
16
14
16
Synthesis of 3-Formylchromones: 3-Formylchromones 2a–h were
synthesized by a modified Harnisch procedure.[12] Phosphorus
oxychloride (1.9 mL, 3.126 g, 20.384 mmol) was added dropwise to
a stirred and cooled (0–5 °C) solution of 2Ј-hydroxyacetophenone
1a–h (10 mmol) in abs. DMF (5 mL) over 30 min, and the reaction
mixture was then allowed to warm to room temperature and was
kept at this temperature for 1 h. (If the stirring of the resulting
[a] Defined as (Y1 ϫee1 + Y2 ϫee2)/(Y1 + Y2); Y = Yield (%).
The moderate ee values (14–23%) are comparable with
those (1–34%) found in the case of 2-methyl-1,4-naphtho-
quinone[32b] and provide further evidence for the conclusion slurry became difficult, a further 3–4 mL of abs. DMF was added.)
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1941

T. Patonay et al.
FULL PAPER
3
3
It was then poured onto crushed ice and stirred for 4 h, and the
solid precipitate was filtered off, washed with water, dried and
recrystallized from hexane/ethyl acetate. The products were iden-
tified by their melting points and 1H NMR spectra. Compounds
(yields): 2a[12] (50%), 2b[13] (71%), 2c[13] (74%), 2d[13] (55%), 2e[33]
(53%), 2g[13] (7%).
(d, JH,H = 7.5 Hz, 2 H, 2Ј,6Ј-H), 7.6 (dd, JH,H = 8.9, 2.6 Hz, 1
H, 7-H), 7.7 (d, 3JH,H = 16.4 Hz, 1 H, β-H), 7.8 (d, 3JH,H = 8.9 Hz,
1 H, 8-H), 8.1 (d, 3JH,H = 2.6 Hz, 1 H, 5-H), 8.7 (s, 1 H, 2-H) ppm.
13C NMR ([D6]DMSO): δ = 119.3 (C-8), 120.5 (C-3), 121.0 (C-α),
124.2 (C-β), 124.5 (C-4a), 126.2 (C-2Ј,6Ј), 127.8 (C-4Ј), 128.8 (C-
3Ј,5Ј), 130.0 (C-6), 131.1 (C-5), 133.9 (C-7), 137.1 (C-1Ј), 149.0 (C-
2), 153.8 (C-8a), 174.4 (C-4) ppm. IR: ν = 1642 (C=O), 1608
˜
1
7-Chloro-3-formylchromone (2f): Yield: 64%, m.p. 183–186 °C. H
(C=C), 1556, 1468, 1448, 1272, 1168, 966, 818, 744 cm–1.
C17H11ClO2 (282.72): calcd. C 72.22, H 3.92; found C 72.45, H
4.09.
3
3
NMR: δ = 7.5 (dd, JH,H = 8.5, 1.9 Hz, 1 H, 6-H), 7.6 (d, JH,H
=
3
1.9 Hz, 1 H, 8-H), 8.2 (d, JH,H = 8.5 Hz, 1 H, 5-H), 8.5 (s, 1 H,
2-H), 10.4 (s, 1 H, 3-CHO) ppm. 13C NMR: δ = 118.8 (C-8), 120.6
(C-4a), 123.9 (C-3), 127.6 (C-6), 135.1 (C-5), 141.2 (C-7), 156.4 (C- (E)-6-Bromo-3-styrylchromone [(E)-3e]: Yellow crystals. Yield: 60%,
3
8a), 160.8 (C-2), 175.3 (C-4), 188.4 (CHO) ppm. IR: ν = 3081, 1655
m.p. 192–195 °C. 1H NMR ([D6]DMSO): δ = 7.1 (d, JH,H
=
˜
(C=O), 1610 (C=C), 1554, 1433, 1341, 1300, 891, 780 cm–1. MS:
m/z (%) = 208 (2) [M]+·, 180 (100) [M – CO], 154 (17) [RDA frag-
ment], 138 (25), 126 (12), 110 (7), 89 (14). C10H5ClO3 (208.60):
calcd. C 57.58, H 2.42; found C 57.77, H 2.29.
16.4 Hz, 1 H, α-H), 7.3 (m, 1 H, 4Ј-H), 7.4 (m, 2 H, 3Ј,5Ј-H), 7.6
3
3
(d, JH,H = 7.6 Hz, 2 H, 2Ј,6Ј-H), 7.7 (d, JH,H = 8.9 Hz, 1 H, 8-
H), 7.8 (d, 3JH,H = 16.4 Hz, 1 H, β-H), 8.0 (dd, 3JH,H = 8.9, 2.4 Hz,
1 H, 7-H), 8.2 (d, 3JH,H = 2.4 Hz, 1 H, 5-H), 8.7 (s, 1 H, 2-H) ppm.
13C NMR ([D6]DMSO): δ = 117.9 (C-6), 119.3 (C-8), 120.5 (C-3),
121.1 (C-α), 124.8 (C-4a), 126.2 (C-2Ј,6Ј), 127.3, 127.8 (C-β, C-4Ј),
128.7 (C-3Ј,5Ј), 131.1 (C-5), 136.6 (C-7), 137.0 (C-1Ј), 154.1 (C-8a),
7-Benzyloxy-3-formylchromone (2h): Yield: 26%, m.p. 148–149 °C.
3
1H NMR: δ = 5.2 (s, 2 H, 7-PhCH2O), 7.0 (d, JH,H = 2.4 Hz, 1
3
H, 8-H), 7.1 (dd, JH,H = 8.9, 2.4 Hz, 1 H, 6-H), 7.3–7.4 (m, 5 H,
155.1 (C-2), 174.3 (C-4) ppm. IR: ν = 1604 (C=O), 1606 (C=C),
˜
3
Ph), 8.2 (d, JH,H = 8.9 Hz, 1 H, 5-H), 8.5 (s, 1 H, 2-H), 10.4 (s, 1
1554, 1464, 1436, 1272, 1152, 748 cm–1. C17H11BrO2 (327.17):
calcd. C 62.41, H 3.39; found C 62.64, H 3.32.
H, 3-CHO) ppm. 13C NMR: δ = 70.8 (7-PhCH2O), 102.3 (C-8),
116.3 (C-6), 119.2, 120.4 (C-3, C-4a), 127.6, 127.7, 128.7, 129.0 (C-
5, C-2Ј,6Ј, C-3Ј,5Ј, C-4Ј), 135.5 (C-1Ј), 158.1 (C-8a), 160.4 (C-2),
(E)-7-Chloro-3-styrylchromone [(E)-3f]: Yellow crystals. Yield: 60%,
3
m.p. 192–195 °C. 1H NMR ([D6]DMSO): δ = 7.1 (d, JH,H
=
164.1 (C-7), 177.7 (C-4), 189.1 (CHO) ppm. IR: ν = 1642 (C=O),
˜
1621 (C=C), 1556, 1441, 1303, 1270, 1242 (C–O–C), 994, 763 cm–1.
MS: m/z (%) = 280 (1) [M]+·, 252 (19) [M – CO], 91 (100) [Bn]+,
65 (13). C17H12O4 (280.27): calcd. C 72.85, H 4.32; found C 73.11,
H 4.28.
16.3 Hz, 1 H, α-H), 7.3 (m, 1 H, 4Ј-H), 7.40 (m, 2 H, 3Ј,5Ј-H), 7.5
3
3
(d, JH,H = 8.1 Hz, 2 H, 2Ј,6Ј-H), 7.6 (dd, JH,H = 8.5, 1.9 Hz, 1
H, 6-H), 7.8 (d, 3JH,H = 16.3 Hz, 1 H, β-H), 7.9 (d, 3JH,H = 1.9 Hz,
1 H, 8-H), 8.1 (d, 3JH,H = 8.5 Hz, 1 H, 5-H), 8.7 (s, 1 H, 2-H) ppm.
13C NMR ([D6]acetone): δ = 120.0 (C-8), 121.0 (C-α), 123.4 (C-3),
124.6 (C-4a), 127.7 (C-6), 128.2 (C-2Ј,6Ј), 129.3, 129.6 (C-β, C-4Ј),
130.5 (C-3Ј,5Ј), 133.6 (C-5), 139.5 (C-1Ј), 140.7 (C-7), 156.5 (C-2),
3-Formyl-7-methoxychromone (2g) was also prepared by the pro-
cedure reported by Zúñiga.[14] The 2,2-difluoro-7-methoxy-4-
methyl-4H-1,3,2-benzodioxaborin intermediate was obtained in
67% yield and transformed into chromone 2g. The crude product
was subjected to column chromatography (eluent: hexane/ethyl ace-
tate, 1:1) to give a 24% yield (calculated based on the 1,3,2-di-
oxaborin intermediate).
157.7 (C-8a), 176.8 (C-4) ppm. IR: ν = 1644, 1626 (C=O), 1608
˜
(C=C), 1556, 1428, 1150, 972, 892, 862, 778, 746, 690 cm–1.
C17H11ClO2 (282.72): calcd. C 72.22, H 3.92; found C 72.13, H
3.99.
(E)-7-Methoxy-3-styrylchromone [(E)-3g]: This compound was
Microwave-Induced Synthesis of (E)-3-Styrylchromones. General
Procedure: A 3-formylchromone 2a–f (0.804 mmol), phenylmalonic
acid (288 mg, 1.599 mmol) and anhydrous sodium acetate (65 mg,
0.792 mmol) were thoroughly mixed without the use of any solvent
in an MW tube and irradiated by using the MW program as fol-
lows. Power: 120 W, ramp time: 180 s; hold time: 240 s; tempera-
ture: 100 °C. After completion of the reaction, the mixture was
treated with water (10 mL), and the solidified precipitate was
washed with water (5ϫ50 mL), then with diisopropyl ether
(30 mL) and dried to give pure chromones 3a–f. The known prod-
purified by column chromatography (eluent: hexane/ethyl acetate,
1
1:1). Yellow crystals. Yield: 47%, m.p. 151–152 °C. H NMR: δ =
3.9 (s, 3 H, 7-OMe), 6.8 (d, 3JH,H = 2.2 Hz, 1 H, 8-H), 6.9 (d, 3JH,H
3
= 16.2 Hz, 1 H, α-H), 7.0 (dd, JH,H = 9.2, 2.2 Hz, 1 H, 6-H), 7.3
(m, 1 H, 4Ј-H), 7.4 (m, 2 H, 3Ј,5Ј-H), 7.5 (m, 2 H, 2Ј,6Ј-H), 7.6 (d,
3JH,H = 16.2 Hz, 1 H, β-H), 8.0 (s, 1 H, 2-H), 8.2 (d, 3JH,H = 9.2 Hz,
1 H, 5-H) ppm. 13C NMR: δ = 55.8 (7-OMe), 100.1 (C-8), 114.7
(C-6), 118.3 (C-3), 119.2 (C-α), 121.7 (C-4a), 126.6 (C-2Ј,6Ј), 127.6,
127.8 (C-5, C-4Ј), 128.6 (C-3Ј,5Ј), 131.5 (C-β), 137.4 (C-1Ј), 152.5
(C-2), 157.6 (C-8a), 164.0 (C-7), 176.0 (C-4) ppm. IR: ν = 3060,
˜
1
ucts were identified by their melting points and H NMR spectra.
3003 (epoxide), 2942, 2838 (MeO), 1640 (C=O), 1616 (C=C), 1439,
1402, 1269, 1243, 1201 (C–O–C and epoxide), 1173, 1097, 1026,
970, 834, 747, 695 cm–1. C18H14O3 (278.30): calcd. C 77.68, H 5.07;
found C 77.54, H 4.94.
Compounds (yields): 3a[4] (61%), 3b[7] (55%).
(E)-6-Methoxy-3-styrylchromone [(E)-3c]: Yellow crystals. Yield:
1
50%, m.p. 123–126 °C. H NMR: δ = 3.9 (s, 3 H, 6-OMe), 7.1 (d,
3JH,H = 16.2 Hz, 1 H, α-H), 7.3 (m, 2 H, 3Ј,5Ј-H), 7.3–7.4 (m, 3 H,
Synthesis of 3-(3-Phenyloxiran-2-yl)chromones by Dimethyldi-
oxirane Oxidation of 3-Styrylchromones. General Procedure: Di-
methyldioxirane solution (40 mL, 0.078  in acetone) was added to
a stirred solution of a 3-styrylchromone [(E)-3a–f or (Z)-3a,b,i–k,
0.75 mmol] in dichloromethane (10 mL), and the mixture was al-
lowed to react at room temperature. The reaction was complete
within 2 h. The reaction mixture was concentrated, and the solid
residue was treated with hexane, filtered and recrystallized from a
solvent (indicated in parentheses) or purified by column
chromatography (1,2-dichloroethane). The reactions of (E)-3-sty-
rylchromones resulted in the formation of trans-3-(3-phenyloxiran-
3
2Ј,4Ј,6Ј-H), 7.5 (m, 2 H, 7-H, 8-H), 7.6 (d, JH,H = 16.2 Hz, 1 H,
β-H), 7.6 (d, 3JH,H = 2.7 Hz, 1 H, 5-H), 8.1 (s, 1 H, 2-H) ppm. 13C
NMR: δ = 55.9 (6-OMe), 105.1 (C-5), 119.2, 119.4 (C-7, C-8), 120.9
(C-3), 123.6 (C-α), 124.6 (C-4a), 126.5 (C-2Ј,6Ј), 127.7 (C-4Ј), 128.6
(C-3Ј,5Ј), 131.4 (C-β), 137.3 (C-1Ј), 150.6 (C-8a), 152.8 (C-2), 157.0
(C-6), 176.3 (C-4) ppm. IR: ν = 1636 (C=O), 1620 (C=C), 1484,
˜
1448, 1324, 1280, 1198 (C–O–C), 1144, 714 cm–1. C18H14O3
(278.30): calcd. C 77.68, H 5.07; found C 77.47, H 4.98.
(E)-6-Chloro-3-styrylchromone [(E)-3d]: Yellowish crystals. Yield:
48%, m.p. 198–201 °C. 1H NMR ([D6]DMSO): δ = 7.1 (d, 3JH,H
=
16.4 Hz, 1 H, α-H), 7.3 (m, 1 H, 4Ј-H), 7.4 (m, 2 H, 3Ј,5Ј-H), 7.5 2-yl)chromones trans-3a–f, whereas the oxidation of (Z)-3-styryl-
1942
www.eurjoc.org
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2008, 1937–1946

Microwave-Induced Synthesis and Selective Epoxidation of 3-Styrylchromones
chromones led exclusively to cis-3-(3-phenyloxiran-2-yl)chromones
cis-3a,b,i–k. No other diastereomer was detected in the worked up
reaction mixtures in any case.
1141, 1127, 874, 787, 713 cm–1. C18H14O4 (294.30): calcd. C 73.46,
H 4.79; found C 73.71, H 4.91.
trans-6-Chloro-3-(3-phenyloxiran-2-yl)chromone (trans-4d): This
compound was purified by column chromatography. Off-white
crystals. Yield: 61%, m.p. 144.5–145.5 °C. 1H NMR: δ = 3.8 (d,
trans-3-(3-Phenyloxiran-2-yl)chromone (trans-4a): Off-white crys-
1
tals. Yield: 88%, m.p. 110–112 °C (hexane/EtOAc). H NMR: δ =
3
3JH,H = 1.7 Hz, 1 H, α-H), 4.1 (d, JH,H = 1.7 Hz, 1 H, β-H), 7.3–
3
3
3.8 (d, JH,H = 1.9 Hz, 1 H, α-H), 4.2 (d, JH,H = 1.9 Hz, 1 H, β-
H), 7.3–7.5 (m, 7 H, 6-H, 8-H, Ph), 7.7 (m, 1 H, 7-H), 7.9 (s, 1 H,
3
3
7.4 (m, 5 H, Ph), 7.5 (d, JH,H = 8.6 Hz, 1 H, 8-H), 7.6 (dd, JH,H
3
2-H), 8.2 (d, JH,H = 7.9 Hz, 1 H, 5-H) ppm. 13C NMR: δ = 56.1
3
= 8.6, 2.2 Hz, 1 H, 7-H), 7.9 (s, 1 H, 2-H), 8.2 (d, JH,H = 2.2 Hz,
1 H, 5-H) ppm. 13C NMR: δ = 55.9 (C-α), 62.5 (C-β), 120.0 (C-8),
121.3 (C-4a), 124.5 (C-3), 125.1 (C-4Ј), 125.8 (C-2Ј,6Ј), 128.5 (C-
3Ј,5Ј), 128.6 (C-5), 131.4 (C-6), 134.1 (C-7), 136.1 (C-1Ј), 152.7 (C-
(C-α), 62.4 (C-β), 118.2 (C-8), 121.1 (C-4a), 123.6 (C-3), 125.4,
125.6 (C-6, C-4Ј), 125.7 (C-2Ј,6Ј), 128.5 (C-5, C-3Ј,5Ј), 133.6 (C-7),
133.7 (C-1Ј), 153.4 (C-2), 156.2 (C-8a), 176.8 (C-4) ppm. IR: ν =
˜
2), 154.7 (C-8a), 175.7 (C-4) ppm. IR: ν = 3084 (epoxide), 1650
˜
3066 (epoxide), 1632 (C=O), 1608 (C=C), 1574, 1468, 1432, 1390,
1350, 1318, 1224 (epoxide), 1168, 876, 856, 762, 732 cm–1.
C17H12O3 (264.28): calcd. C 77.26, H 4.58; found C 77.39, H 4.76.
(C=O), 1606 (C=O), 1466, 1446, 1350, 1156, 826, 698 cm–1.
C17H11ClO3 (298.72): calcd. C 68.35, H 3.71; found C 68.12, H
3.96.
cis-3-(3-Phenyloxiran-2-yl)chromone (cis-4a): Off-white crystals.
Yield: 80%, m.p. 175–176.5 °C (hexane). 1H NMR: δ = 4.4 (d,
trans-6-Bromo-3-(3-phenyloxiran-2-yl)chromone (trans-4e): This
compound was purified by column chromatography. Off-white
3
3JH,H = 4.2 Hz, 1 H, α-H), 4.5 (d, JH,H = 4.2 Hz, 1 H, β-H), 7.2–
1
3
crystals. Yield: 95%, m.p. 154–156 °C. H NMR: δ = 3.8 (d, JH,H
7.4 (m, 7 H, 6-H, 8-H, Ph), 7.6 (m, 1 H, 7-H), 7.7 (s, 1 H, 2-H),
= 1.8 Hz, 1 H, α-H), 4.2 (d, 3JH,H = 1.8 Hz, 1 H, β-H), 7.3–7.4 (m,
3
8.1 (d, JH,H = 8.5 Hz, 1 H, 5-H) ppm. 13C NMR: δ = 54.0 (C-α),
3
6 H, 8-H, Ph), 7.8 (dd, JH,H = 9.0, 2.4 Hz, 1 H, 7-H), 7.9 (s, 1 H,
59.5 (C-β), 118.1 (C-8), 118.2 (C-4a), 123.3 (C-3), 125.2, 125.5 (C-
6, C-4Ј), 126.6 (C-2Ј,6Ј), 127.8 (C-5), 128.0 (C-3Ј,5Ј), 133.8 (C-7),
2-H), 8.3 (d, JH,H = 2.4 Hz, 1 H, 5-H) ppm. 13C NMR: δ = 55.9
3
(C-α), 62.5 (C-β), 118.9 (C-6), 120.2 (C-8), 121.5 (C-4a), 124.9 (C-
3), 125.8 (C-2Ј,6Ј), 128.5 (C-3Ј,5Ј), 128.3, 128.6 (C-4Ј, C-5), 136.1
(C-1Ј), 136.8 (C-7), 152.6 (C-2), 155.1 (C-8a), 175.7 (4-C) ppm. IR:
136.3 (C-1Ј), 152.4 (C-2), 156.3 (C-8a), 176.9 (C-4) ppm. IR: ν =
˜
3060 (epoxide), 1654 (C=O), 1612 (C=C), 1466, 1346, 1312, 1218
(epoxide), 1196, 854, 824, 760, 746 cm–1. C17H12O3 (264.28): calcd.
C 77.26, H 4.58; found C 77.12, H 4.54.
ν = 3062 (epoxide), 1648 (C=O), 1604 (C=C), 1460, 1442, 1304,
˜
1210 (epoxide), 1154, 878, 824, 780, 736, 696 746 cm–1. C17H11BrO3
(343.17): calcd. C 59.50, H 3.23; found C 59.55, H 3.40.
trans-6-Methyl-3-(3-phenyloxiran-2-yl)chromone (trans-4b): This
compound was purified by column chromatography. Off-white
crystals. Yield: 55%, m.p. 130–131 °C. H NMR: δ = 2.5 (s, 3 H,
trans-7-Chloro-3-(3-phenyloxiran-2-yl)chromone (trans-4f): Off-
1
1
white crystals. Yield: 74%, m.p. 174–177 °C (hexane). H NMR: δ
3
3
6-Me), 3.8 (d, JH,H = 2.0 Hz, 1 H, α-H), 4.2 (d, JH,H = 2.0 Hz, 1
3
3
= 3.8 (d, JH,H = 1.6 Hz, 1 H, α-H), 4.1 (d, JH,H = 1.6 Hz, 1 H,
β-H), 7.3–7.4 (m, 6 H, 6-H, Ph), 7.5 (d, 3JH,H = 2.0 Hz, 1 H, 8-H),
7.9 (s, 1 H, 2-H), 8.2 (d, 3JH,H = 8.6 Hz, 1 H, 5-H) ppm. 13C NMR:
δ = 55.9 (C-α), 62.5 (C-β), 118.3 (C-8), 121.7 (C-4a), 122.2 (C-3),
125.8 (C-2Ј,6Ј), 126.3 (C-4Ј), 127.1 (C-6), 128.5 (C-3Ј,5Ј), 128.6 (C-
5), 136.1 (C-1Ј), 140.0 (C-7), 152.5 (C-2), 156.5 (C-8a), 176.1 (C-4)
3
H, β-H), 7.3–7.4 (m, 6 H, 8-H, Ph), 7.5 (dd, JH,H = 8.3, 1.4 Hz, 1
3
H, 7-H), 7.9 (s, 1 H, 2-H), 8.0 (d, JH,H = 1.4 Hz, 1 H, 5-H) ppm.
13C NMR: δ = 20.9 (6-Me), 56.2 (C-α), 62.4 (C-β), 117.9 (C-8),
120.9 (C-4a), 123.3 (C-3), 124.9 (C-4Ј), 125.7 (C-2Ј,6Ј), 128.5 (C-5,
C-3Ј,5Ј), 135.1 (C-7), 135.4, 136.9 (C-6, C-1Ј), 152.4 (C-2), 154.6
(C-8a), 176.9 (C-4) ppm. IR: ν = 3072 (epoxide), 1650 (C=O), 1616
˜
ppm. IR: ν = 3076 (epoxide), 1654 (C=O), 1608 (C=C), 1560, 1440,
˜
(C=C), 1576, 1484, 1458, 1420, 1340, 1314, 1232 (epoxide), 1204,
1168, 1144, 870, 836, 782, 716 cm–1. C18H14O3 (278.30): calcd. C
77.68, H 5.07; found C 77.84, H 4.89.
1428, 1356, 1210 (epoxide), 1154, 870, 810, 790, 756, 702 cm–1.
C17H11ClO3 (298.72): calcd. C 68.35, H 3.71; found C 68.49, H
3.77.
cis-6-Methyl-3-(3-phenyloxiran-2-yl)chromone (cis-4b): Off-white
crystals. Yield: 80%, m.p. 146–147 °C (hexane). H NMR: δ = 2.4
cis-3-[3-(4-Ethoxyphenyl)oxiran-2-yl]chromone (cis-4i): Off-white
1
1
crystals. Yield: 92%, m.p. 140–142 °C (iPr2O/hexane). H NMR: δ
3
3
3
3
(s, 3 H, 6-Me), 4.4 (d, JH,H = 3.9 Hz, 1 H, α-H), 4.5 (d, JH,H
=
= 1.4 (t, JH,H = 6.8 Hz, 1 H, Me), 3.9 (q, JH,H = 6.8 Hz, 2 H,
3
3
3
3.9 Hz, 1 H, β-H), 7.1–7.3 (m, 6 H, 8-H, Ph), 7.4 (dd, JH,H = 8.3,
CH2), 4.4 (d, JH,H = 4.0 Hz, 1 H, α-H), 4.5 (d, JH,H = 4.0 Hz, 1
H, β-H), 6.8 (d, JH,H = 8.3 Hz, 2 H, 3Ј,5Ј-H), 7.2 (d, JH,H
3
3
3
1.5 Hz, 1 H, 7-H), 7.7 (s, 1 H, 2-H), 7.9 (d, JH,H = 1.5 Hz, 1 H,
=
5-H) ppm. 13C NMR: δ = 20.8 (6-Me), 54.0 (C-α), 59.5 (C-β), 117.9
(C-8), 118.0 (C-4a), 123.0 (C-3), 124.7 (C-4Ј), 126.7 (C-2Ј,6Ј), 127.7
(C-5), 128.0 (C-3Ј,5Ј), 134.9 (C-7), 133.8, 135.2 (C-6, C-1Ј), 153.4
8.3 Hz, 2 H, 2Ј,6Ј-H), 7.3–7.4 (m, 2 H, 6-H, 8-H), 7.6 (m, 1 H, 7-
3
H), 7.7 (s, 1 H, 2-H), 8.2 (d, JH,H = 7.9 Hz, 1 H, 5-H) ppm. 13C
NMR: δ = 14.7 (Me), 54.0 (C-α), 59.3 (C-β), 63.3 (CH2), 114.1 (C-
2Ј,6Ј), 118.1 (C-8), 118.3 (C-4a), 123.4 (C-3), 125.2, 125.5 (C-5, C-
6), 125.6 (C-1Ј), 127.8 (C-3Ј,5Ј), 133.6 (C-7), 153.5 (C-2), 156.2 (C-
(C-2), 154.5 (C-8a), 176.9 (C-4) ppm. IR: ν = 3030 (epoxide), 1648
˜
(C=O), 1616 (C=C), 1486, 1448, 1438, 1336, 1312, 1234 (epoxide),
1200, 1168, 884, 844, 818, 744, 700 cm–1. C18H14O3 (278.30): calcd.
C 77.68, H 5.07; found C 77.59, H 5.00.
8a), 158.5 (C-4Ј), 176.9 (C-4) ppm. IR: ν = 3074 (epoxide), 2874
˜
(OEt), 1646 (C=O), 1610 (C=C), 1512, 1466, 1348, 1242 (C–O–Et),
1172, 1052 (C–O–Et), 820, 756 cm–1. C19H16O4 (308.33): calcd. C
74.01, H 5.23; found C 74.16, H 5.11.
trans-6-Methoxy-3-(3-phenyloxiran-2-yl)chromone (trans-4c): Off-
1
white crystals. Yield: 71%, m.p. 134–138 °C (hexane). H NMR: δ
3
= 3.8 (d, JH,H = 1.5 Hz, 1 H, α-H), 3.9 (s, 3 H, 6-OMe), 4.2 (d,
cis-3-[3-(4-Nitrophenyl)oxiran-2-yl]chromone (cis-4j): Off-white
3
1
3JH,H = 1.5 Hz, 1 H, β-H), 7.2 (dd, JH,H = 9.0, 2.9 Hz, 1 H, 7-H),
crystals. Yield: 93%, m.p. 185–187 °C (iPr2O/hexane). H NMR: δ
3
3
3
7.3–7.4 (m, 5 H, Ph), 7.5 (d, JH,H = 9.0 Hz, 1 H, 7-H), 7.6 (d,
= 4.5 (d, JH,H = 4.0 Hz, 1 H, α-H), 4.6 (d, JH,H = 4.0 Hz, 1 H,
3JH,H = 2.9 Hz, 1 H, 5-H), 7.9 (s, 1 H, 2-H) ppm. 13C NMR: δ =
55.9, 56.2 (C-α, 6-MeO), 62.4 (C-β), 104.6 (C-5), 119.6 (C-8), 120.3
β-H), 7.4 (m, 2 H, 6-H, 8-H), 7.5 (d, JH,H = 8.3 Hz, 2 H, 2Ј,6Ј-
3
H), 7.6 (m, 1 H, 7-H), 7.8 (s, 1 H, 2-H), 8.1 (overlapping d’s, 3 H,
(C-4a), 124.0 (C-7), 124.2 (C-3), 125.7 (C-2Ј,6Ј), 128.5 (C-3Ј,5Ј), 5-H, 3Ј,5Ј-H) ppm. 13C NMR: δ = 54.6 (C-α), 58.4 (C-β), 117.7 (C-
136.3 (C-1Ј), 151.2 (C-8a), 152.3 (C-2), 157.1 (C-6), 176.7 (C-4)
4a), 118.2 (C-8), 123.2 (C-3), 123.3 (C-2Ј,6Ј), 125.4, 125.5 (C-5, C-
ppm. IR: ν = 3060 (epoxide), 2968, 2943, 2842 (OMe), 1646 (C=O), 6), 127.5 (C-3Ј,5Ј), 134.0 (C-7), 141.2 (C-1Ј), 147.6 (C-4Ј), 153.2 (C-
˜
1612 (C=C), 1484, 1470, 1439, 1313, 1248, 1202 (epoxide), 1183,
2), 156.2 (C-8a), 176.5 (C-4) ppm. IR: ν = 1646 (C=O), 1610
˜
Eur. J. Org. Chem. 2008, 1937–1946
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
1943

T. Patonay et al.
FULL PAPER
(C=C), 1522 (NO2), 1466, 1348 (NO2), 1106, 860, 760 cm–1.
C17H11NO5 (309.27): calcd. C 66.02, H 3.58, N 4.53; found C
65.87, H 3.42, N 4.75.
1
m.p. 93–96 °C (hexane). H NMR: δ = 2.4 (s, 3 H, 6-Me), 5.5 (s, 1
H, 2-H), 6.8 (d, 3JH,H = 16.2 Hz, 1 H, β-H), 6.9 (d, 3JH,H = 16.2 Hz,
1 H, α-H), 7.0 (d, JH,H = 8.7 Hz, 1 H, 8-H), 7.3–7.4 (m, 4 H, 7-
3
3
H, 3Ј,5Ј-H, 4Ј-H), 7.5 (d, JH,H = 7.2 Hz, 2 H, 2Ј,6Ј-H), 7.8 (s, 1
cis-3-[3-(4-Chlorophenyl)oxiran-2-yl]-6-methylchromone
(cis-4k):
H, 5-H) ppm. 13C NMR: δ = 20.5 (6-Me), 62.3 (C-3), 83.6 (C-2),
117.7, 117.8 (C-8, C-4Ј), 119.7 (C-1Ј), 126.9 (C-2Ј,6Ј), 127.2 (C-α),
128.6 (C-β), 128.7 (C-3Ј,5Ј), 133.1 (C-6), 133.7 (C-5), 135.5 (C-4a),
Off-white crystals. Yield: 96%, m.p. 144–147 °C (hexane). 1H
3
NMR: δ = 2.4 (s, 3 H, 6-Me), 4.4 (dd, JH,H = 4.3, 1.1 Hz, 1 H, α-
3
H), 4.5 (d, JH,H = 4.3 Hz, 1 H, β-H), 7.2 (br. s, 4 H, 2Ј,3Ј,5Ј,6Ј-
137.1 (C-7), 153.2 (C-8a), 188.5 (C-4) ppm. IR: ν = 3060, 3026
˜
3
3
H), 7.3 (d, JH,H = 8.5 Hz, 1 H, 8-H), 7.4 (dd, JH,H = 8.6, 2.2 Hz,
1 H, 7-H), 7.7 (d, 3JH,H = 1.1 Hz, 1 H, 2-H), 7.9 (d, 3JH,H = 2.2 Hz,
1 H, 5-H) ppm. 13C NMR: δ = 20.5 (6-Me), 54.1 (C-α), 58.7 (C-
β), 117.9 (C-4a), 118.0 (C-8), 123.1 (C-3), 124.9 (C-5), 128.1, 128.4
(C-2Ј,6Ј, C-3Ј,5Ј), 132.6, 133.8 (C-6, C-4Ј), 135.2 (C-7), 135.5 (C-
(epoxide), 2920 (Me), 1678 (C=O), 1618 (C=C), 1488, 1450, 1424,
1318, 1296, 1216 (epoxide), 1204, 1130, 1104, 966, 922, 826, 800,
738 cm–1. C18H14O3 (278.30): calcd. C 77.68, H 5.07; found C
77.83, H 4.92.
1Ј), 153.6 (C-2), 154.8 (C-8a), 177.2 (C-4) ppm. IR: ν = 1650
˜
(Z)-2,3-Epoxy-6-methyl-3-styrylchroman-4-one [(Z)-5b]: This reac-
(C=O), 1619 (C=C), 1488, 1436, 1424, 1317, 1166, 1088, 843 cm–1.
C18H13ClO3 (312.75): calcd. C 69.13, H 4.19; found C 68.97, H
4.03.
tion was performed in dioxane solution. White crystals. Yield: 69%,
1
m.p. 93–96 °C (hexane). H NMR: δ = 2.3 (s, 3 H, 6-Me), 5.2 (s, 1
H, 2-H), 6.0 (d, 3JH,H = 11.9 Hz, 1 H, α-H), 6.9 (d, 3JH,H = 7.9 Hz,
3
1 H, 8-H), 7.0 (d, JH,H = 11.9 Hz, 1 H, β-H), 7.1–7.3 (m, 5 H,
Synthesis of 2,3-Epoxy-3-styrylchroman-4-ones by Weitz–Scheffer
Oxidation of 3-Styrylchromones. General Procedure: Hydrogen per-
oxide (30%, 0.5 mL) and then sodium hydroxide solution (8%
0.24 mL) were added to a cooled (0 °C) and stirred solution of a
3-styrylchromone [(E)-3a–f or (Z)-3a,b,i–k (0.400 mmol)] in ace-
tone or 1,4-dioxane (5 mL), and the reaction was monitored by
TLC (PhMe). After completion of the reaction (0.25–1.5 h), the
mixture was poured onto crushed ice, and the precipitate was fil-
tered off and crystallized from hexane or hexane/ethyl acetate. The
reactions of (E)-3-styrylchromones resulted in the formation of (E)-
2,3-epoxy-3-styrylchroman-4-ones (E)-5a–f, whereas the oxidation
of (Z)-3-styrylchromones led exclusively to (Z)-2,3-epoxy-3-sty-
rylchroman-4-ones (Z)-5a,b,i–k. No other diastereomer or re-
gioisomer was detected in the worked up reaction mixture in any
case.
3
Ph), 7.4 (3JH,H = 7.9 Hz, 1 H, 7-H), 7.8 (dd, JH,H = 8.0, 1.4 Hz, 1
H, 5-H) ppm. 13C NMR: δ = 20.5 (6-Me), 61.2 (C-3), 82.8 (C-2),
117.8 (C-8), 119.1 (C-1Ј), 120.1 (C-α), 127.2 (C-5), 128.2 (C-2Ј,6Ј),
128.3 (C-4Ј), 128.5 (C-3Ј,5Ј), 133.1 (C-6), 135.4 (C-4a), 137.0, 137.2
(C-7, C-β), 153.3 (C-8a), 188.3 (C-4) ppm. IR: ν = 3066, 3028 (ep-
˜
oxide), 1680 (C=O), 1618 (C=C), 1488, 1312, 1218 (epoxide), 1206,
1132, 1090, 934, 806 cm–1. C18H14O3 (278.30): calcd. C 77.68, H
5.07; found C 77.60, H 5.17.
(E)-2,3-Epoxy-6-methoxy-3-styrylchroman-4-one [(E)-5c]: This reac-
tion was performed in dioxane solution. White crystals. Yield: 34%,
1
m.p. 76–78 °C (hexane). H NMR: δ = 3.8 (s, 3 H, 6-OMe), 5.5 (s,
3
3
1 H, 2-H), 6.8 (d, JH,H = 16.2 Hz, 1 H, β-H), 6.9 (d, JH,H
=
3
16.2 Hz, 1 H, α-H), 7.1 (d, JH,H = 9.0 Hz, 1 H, 8-H), 7.2 (dd,
3JH,H = 9.0, 2.9 Hz, 1 H, 7-H), 7.3–7.4 (m, 4 H, 5-H, 3Ј,5Ј-H, 4Ј-
H), 7.5 (d, 3JH,H = 7.2 Hz, 2 H, 2Ј,6Ј-H) ppm. 13C NMR: δ = 56.2
(6-MeO), 62.4 (C-3), 83.9 (C-2), 108.1 (C-8), 118.1 (C-7), 119.5 (C-
4Ј), 120.5 (C-1Ј), 125.5 (C-α), 127.3 (C-2Ј,6Ј), 128.9 (C-β), 129.0
(C-3Ј,5Ј), 134.1 (C-5), 135.9 (C-4a), 149.9 (C-8a), 155.8 (C-6), 188.7
(E)-2,3-Epoxy-3-styrylchroman-4-one [(E)-5a]: This reaction was
performed in acetone solution. Yellowish crystals. Yield: 52%, m.p.
135–137 °C (hexane/ethyl acetate). 1H NMR: δ = 5.5 (s, 1 H, 2-H),
3
3
6.8 (d, JH,H = 16.2 Hz, 1 H, β-H), 6.9 (d, JH,H = 16.2 Hz, 1 H,
3
(C-4) ppm. IR: ν = 3059, 3027 (epoxide), 2937, 2945, 2834 (MeO),
˜
α-H), 7.1 (d, JH,H = 8.6 Hz, 1 H, 8-H), 7.2 (m, 1 H, 6-H), 7.3–7.4
3
1680 (C=O), 1617 (C=C), 1490, 1443, 1431, 1292, 1274, 1201 (ep-
oxide), 1142, 1077, 1030, 822, 757, 700 cm–1. C18H14O4 (294.30):
calcd. C 73.46, H 4.79; found C 73.51, H 4.75.
(m, 3 H, 3Ј,5Ј-H, 4Ј-H), 7.5 (d, JH,H = 7.6 Hz, 2 H, 2Ј,6Ј-H), 7.6
(m, 1 H, 7-H), 8.0 (d, JH,H = 8.6 Hz, 1 H, 5-H) ppm. 13C NMR:
3
δ = 62.3 (C-3), 83.6 (C-2), 117.5, 117.9 (C-6, C-8), 120.1 (C-1Ј),
123.4 (C-4Ј), 126.9 (C-2Ј,6Ј), 127.6 (C-α), 128.6 (C-β), 128.7 (C-
3Ј,5Ј), 133.8 (C-5), 135.5 (C-4a), 136.0 (C-7), 155.1 (C-8a), 188.3
(E)-6-Chloro-2,3-epoxy-3-styrylchroman-4-one [(E)-5d]: This reac-
tion was performed in acetone solution. Brownish crystals. Yield:
51%, m.p. 119–122 °C (hexane/ethyl acetate). 1H NMR: δ = 5.5 (s,
(C-4) ppm. IR: ν = 3060, 3034 (epoxide), 1678 (C=O), 1654, 1604
˜
(C=C), 1584, 1478, 1464, 1350, 1330, 1304, 1278, 1208 (epoxide),
1148, 1102, 1080, 960, 908, 834, 762, 742 760 cm–1. C17H12O3
(264.28): calcd. C 77.26, H 4.58; found C 77.28, H 4.25. When the
reaction was performed with benzyltrimethylammonium hydroxide
(Triton B, 90 µL of a 40% methanolic solution), (E)-5a was ob-
tained in 63% yield, m.p. 131–134 °C.
3
3
1 H, 2-H), 6.7 (d, JH,H = 16.6 Hz, 1 H, β-H), 6.8 (d, JH,H
=
3
16.6 Hz, 1 H, α-H), 7.1 (d, JH,H = 9.0 Hz, 1 H, 8-H), 7.3–7.4 (m,
3
3 H, 3Ј,5Ј-H, 4Ј-H), 7.5 (d, JH,H = 7.2 Hz, 2 H, 2Ј,6Ј-H), 7.6 (dd,
3JH,H = 9.0, 2.5 Hz, 1 H, 7-H), 7.9 (d, JH,H = 2.5 Hz, 1 H, 5-H)
3
ppm. 13C NMR: δ = 62.1 (C-3), 83.6 (C-2), 116.9 (C-8), 119.6 (C-
4Ј), 121.0 (C-1Ј), 127.0 (C-2Ј,6Ј,α), 128.7 (C-3Ј,5Ј,β), 129.0 (C-6),
134.2 (C-5), 135.3 (C-4a), 135.9 (C-7), 153.5 (C-8a), 187.3 (C-4)
(Z)-2,3-Epoxy-3-styrylchroman-4-one [(Z)-5a]: This reaction was
performed in acetone solution. Yellowish oil. Yield: 81%. 1H
ppm. IR: ν = 3058, 3024 (epoxide), 1684 (C=O), 1608 (C=C), 1472,
˜
3
1428, 1304, 1266, 1204 (epoxide), 1154, 1108, 968, 920, 820, 792,
746 cm–1. C17H11ClO3 (298.72): calcd. C 68.35, H 3.71; found C
68.55, H 3.87.
NMR: δ = 5.2 (s, 1 H, 2-H), 6.0 (d, JH,H = 11.9 Hz, 1 H, α-H),
3
3
7.0 (d, JH,H = 11.9 Hz, 1 H, β-H), 7.1 (d, JH,H = 8.3 Hz, 1 H, 8-
3
H), 7.2 (m, 6 H, 6-H, Ph), 7.6 (m, 1 H, 7-H), 8.0 (dd, JH,H = 8.0,
1.4 Hz, 1 H, 5-H) ppm. 13C NMR: δ = 61.1 (C-3), 82.8 (C-2), 118.0
(C-8), 119.5 (C-1Ј), 120.0 (C-α), 123.4 (C-6), 127.5 (C-5), 128.3 (C-
2Ј,6Ј), 128.4 (C-4Ј), 128.6 (C-3Ј,5Ј), 135.4 (C-4a), 136.2 (C-7), 137.2
(E)-6-Bromo-2,3-epoxy-3-styrylchroman-4-one [(E)-5e]: This reac-
tion was performed in dioxane solution. White crystals. Yield: 58%,
1
m.p. 113–116 °C (hexane/ethyl acetate). H NMR: δ = 5.5 (s, 1 H,
(C-β), 155.2 (C-8a), 188.1 (C-4) ppm. IR: ν = 3028 (epoxide), 1688,
˜
3
3
2-H), 6.7 (d, JH,H = 16.2 Hz, 1 H, β-H), 6.8 (d, JH,H = 16.2 Hz,
1682 (C=O), 1608 (C=C), 1464, 1336, 1208 (epoxide), 1120, 1082,
758, 700 cm–1. C17H12O3 (264.28): calcd. C 77.26, H 4.58; found C
77.39, H 4.43.
1 H, α-H), 7.0 (d, 3JH,H = 8.6 Hz, 1 H, 8-H), 7.3–7.4 (m, 3 H, 3Ј,5Ј-
3
3
H, 4Ј-H), 7.5 (d, JH,H = 7.2 Hz, 2 H, 2Ј,6Ј-H), 7.7 (dd, JH,H
=
8.6, 2.0 Hz, 1 H, 7-H), 8.1 (d, JH,H = 2.0 Hz, 1 H, 5-H) ppm. 13C
NMR: δ = 62.2 (C-3), 83.6 (C-2), 116.2 (C-1Ј), 116.9 (C-8), 120.0
(C-4Ј), 121.5 (C-6), 127.0 (C-2Ј,6Ј), 128.5 (C-3Ј,5Ј,α), 130.0 (C-β),
3
(E)-2,3-Epoxy-6-methyl-3-styrylchroman-4-one [(E)-5b]: This reac-
tion was performed in dioxane solution. White crystals. Yield: 27%,
1944
www.eurjoc.org
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2008, 1937–1946

Microwave-Induced Synthesis and Selective Epoxidation of 3-Styrylchromones
134.2 (C-5), 135.3 (C-4a), 138.7 (C-7), 154.0 (C-8a), 187.1 (C-4) Enantioselective Epoxidation of (E)-3-Styrylchromone in the Pres-
ppm. IR: ν = 3056 (epoxide), 1684 (C=O), 1636, 1602 (C=O), 1470,
ence of Chiral, Nonracemic PTCs. General Procedure: Hydrogen
˜
1422, 1268, 1206 (epoxide), 1154, 1128, 1106, 820, 792, 746,
peroxide (30%, 0.6 mL), then the catalyst (25 mol-%) and finally
692 cm–1. C17H11BrO3 (343.17): calcd. C 59.50, H 3.23; found C sodium hydroxide solution (8%, 0.1 mL) were added to a stirred
59.36, H 3.21.
solution of (E)-3-styrylchromone (E)-3a (100 mg, 0.403 mmol) in
1,4-dioxane (3 mL). The mixture was stirred at room temperature,
and the reaction was monitored by TLC (PhMe). After ca. 20 min,
a solid started to precipitate. When the reaction was complete, the
solid was filtered off and washed with a copious amount of water.
A second fraction of the precipitate was obtained from the mother
liquor by treatment with water. The two precipitates were analyzed
separately; the ee values were determined by CSP-HPLC. The re-
sults are shown in Table 1.
(E)-7-Chloro-2,3-epoxy-3-styrylchroman-4-one [(E)-5f]: This reac-
tion was performed in dioxane solution. White crystals. Yield: 61%,
1
m.p. 75–77 °C (hexane/ethyl acetate). H NMR: δ = 5.5 (s, 1 H, 2-
3
3
H), 6.7 (d, JH,H = 16.3 Hz, 1 H, β-H), 6.8 (d, JH,H = 16.3 Hz, 1
3
H, α-H), 7.1 (s, 1 H, 8-H), 7.2 (d, JH,H = 8.5 Hz, 1 H, 6-H), 7.3–
3
7.4 (m, 3 H, 3Ј,5Ј-H, 4Ј-H), (d, JH,H = 7.2 Hz, 2 H, 2Ј,6Ј-H), 7.9
3
(d, JH,H = 8.5 Hz, 1 H, 5-H) ppm. 13C NMR: δ = 62.1 (C-3), 83.7
(C-2), 117.0, 118.1 (C-6, C-8), 118.6 (C-1Ј), 124.2 (C-4Ј), 127.0 (C-
2Ј,6Ј,α), 128.7 (C-β), 128.8 (C-3Ј,5Ј), 134.2 (C-5), 135.3 (C-7), 142.1
(C-4a), 155.4 (C-8a), 187.3 (C-4) ppm. IR: ν = 3060, 3024 (epox-
˜
Acknowledgments
ide), 2924, 1684 (C=O), 1604 (C=C), 1576, 1428, 1204 (epoxide),
1088, 964, 916, 798, 746 cm–1. C17H11ClO3 (298.72): calcd. C 68.35,
H 3.71; found C 68.29, H 3.54.
Financial support from the Pázmány Péter Programme (NKTH,
RET 006/2004) and the Hungarian Scientific Research Fund
(OTKA, NI61336) is greatly appreciated.
(Z)-2,3-Epoxy-3-(4Ј-nitrostyryl)chroman-4-one [(Z)-5i]: This reac-
tion was performed in dioxane solution. White crystals. Yield: 82%,
1
m.p. 170–173 °C (hexane/ethyl acetate). H NMR: δ = 5.3 (s, 1 H,
[1] a) G. Doria, G. Romeo, A. Forgione, P. Sberze, N. Tibolla,
M. L. Corno, G. Cruzzola, G. Cadelli, Eur. J. Med. Chem.
1979, 14, 347–351; b) W. H. Gerwick, A. Lopez, G. D.
Van Duyne, J. Clardy, W. Ortiz, A. Baez, Tetrahedron Lett.
1986, 27, 1979–1982; c) W. H. Gerwick, J. Nat. Prod. 1989, 52,
252–256; d) J. D. Brion, G. La Baut, F. Zammattio, A. Pierre,
G. Atassi, L. Belachmi, Eur. Pat. Appl. EP454,587, 1991;
Chem. Abstr. 1992, 116, 106092; e) N. Desideri, C. Conti, F.
Mastropaolo, Antiviral Chem. Chemother. 2000, 11, 373–381; f)
F. Peixoto, A. I. R. N. A. Barros, A. M. S. Silva, J. Biochem.
Mol. Toxicol. 2002, 16, 220–226; g) E. Fernandes, M. Carvalho,
F. Carvalho, A. M. S. Silva, C. M. M. Santos, D. C. G. A.
Pinto, J. A. S. Cavaleiro, M. L. Bastos, Arch. Toxicol. 2003, 77,
500–505; h) P. Filipe, A. M. S. Silva, P. Morliere, C. M. Brito,
L. K. Patterson, G. L. Hug, J. N. Silva, J. A. S. Cavaleiro, J. C.
Maziére, J. P. Freitas, R. Santus, Biochem. Pharmacol. 2004, 67,
2207–2218; i) S. Takamatsu, D. G. Nagle, W. H. Gerwick,
Planta Med. 2004, 70, 127–131; j) K. Y. Lee, D. H. Nam, C. S.
Moon, S. H. Seo, J. Y. Lee, Y. S. Lee, Eur. J. Med. Chem. 2006,
41, 991–996.
[2] M. Ono, Y. Maya, M. Haratake, M. Nakayama, Bioorg. Med.
Chem. 2007, 15, 444–450.
[3] a) W. A. Price, A. M. S. Silva, J. A. S. Cavaleiro, Heterocycles
1993, 36, 2601–2612; b) A. M. S. Silva, D. C. G. A. Pinto,
J. A. S. Cavaleiro, A. Lévai, T. Patonay, ARKIVOC 2004, 7,
106–123.
[4] S. G. Davies, B. E. Mobbs, C. J. Goodwin, J. Chem. Soc. Perkin
Trans. 1 1987, 2597–2604.
[5] A. M. S. Silva, J. A. S. Cavaleiro, J. Elguero, Liebigs Ann./Re-
cueil 1997, 2065–2068.
3
3
2-H), 6.2 (d, JH,H = 11.9 Hz, 1 H, α-H), 7.0 (d, JH,H = 11.9 Hz,
3
1 H, β-H), 7.1 (d, JH,H = 8.6 Hz, 1 H, 8-H), 7.2 (m, 1 H, 6-H),
3
7.4 (d, JH,H = 8.3 Hz, 2 H, 2Ј,6Ј-H), 7.6 (m, 1 H, 7-H), 8.0 (d,
3JH,H = 8.6 Hz, 1 H, 5-H), 8.2 (d, JH,H = 8.3 Hz, 2 H, 3Ј,5Ј-H)
3
ppm. 13C NMR: δ = 61.1 (C-3), 82.4 (C-2), 118.0 (C-8), 119.3 (C-
1Ј), 123.6 (C-6), 123.7 (C-2Ј,6Ј,α), 127.7 (C-5), 129.0 (C-3Ј,5Ј),
134.9 (C-β), 136.5 (C-7), 141.9 (C-4a), 147.3 (C-4Ј), 155.0 (C-8a),
187.5 (C-4) ppm. IR: ν = 3054 (epoxide), 1670 (C=O), 1608 (C=C),
˜
1518 (NO2), 1480, 1464 (NO2), 1346, 1314, 1206 (epoxide), 1150,
1100, 878, 856, 758 cm–1. C17H11NO5 (309.27): calcd. C 66.02, H
3.58; found C 65.87, H 3.35.
(Z)-3-(4Ј-Chlorostyryl)-2,3-epoxy-6-methylchroman-4-one [(Z)-5j]:
This reaction was performed in dioxane solution. White crystals.
Yield: 78%, m.p. 98–101 °C (hexane). 1H NMR: δ = 2.4 (s, 3 H, 6-
3
Me), 5.2 (s, 1 H, 2-H), 6.0 (d, JH,H = 11.9 Hz, 1 H, α-H), 6.9 (d,
3
3JH,H = 11.9 Hz, 1 H, β-H), 7.0 (d, JH,H = 8.3 Hz, 1 H, 8-H), 7.1
(d, 3JH,H = 8.3 Hz, 2 H, 2Ј,6Ј-H), 7.2 (d, 3JH,H = 8.3 Hz, 2 H, 3Ј,5Ј-
H), 7.4 (dd, 3JH,H = 8.3, 1.8 Hz, 1 H, 7-H), 7.78 (d, 3JH,H = 1.8 Hz,
1 H, 5-H) ppm. 13C NMR: δ = 20.5 (6-Me), 61.1 (C-3), 82.6 (C-
2), 117.8 (C-8), 119.1 (C-1Ј), 120.8 (C-α), 127.3 (C-5), 128.7, 129.5
(C-2Ј,6Ј, C-3Ј,5Ј), 133.2, 133.9, 134.2 (C-4a, C-6, C-4Ј), 135.8 (C-
β), 137.4 (C-7), 153.2 (C-8a), 188.1 (C-4) ppm. IR: ν = 3064 (epox-
˜
ide), 2920 (Me), 1680 (C=O), 1618 (C=C), 1490, 1432, 1320, 1212
(epoxide), 1136, 1088, 1078, 940, 826, 792 cm–1. C18H13ClO3
(312.75): calcd. C 69.13, H 4.19; found C 68.99, H 4.28.
Synthesis of Quaternary Quinidinium and Cinchoninium Phase-
Transfer Catalysts: Catalysts Cat 1, Cat 2 and Cat 4 were synthe-
sized according to a literature method.[32b] The same synthetic pro-
cedure (THF at reflux with 1 equiv. of alkylating agent) was used
for the synthesis of the new compound Cat 3.
[6] R. Alonso, A. Brossi, Tetrahedron Lett. 1988, 29, 735–738.
[7] A. Sandulache, A. M. S. Silva, D. C. G. A. Pinto, L. M. P. M.
Almeida, J. A. S. Cavaleiro, New J. Chem. 2003, 27, 1592–1598.
[8] a) B. K. Karale, V. P. Chavan, R. V. Hangarge, A. S. Mane,
C. H. Gill, M. S. Shingare, Indian J. Heterocycl. Chem. 2001,
11, 81–82; b) S. A. Sonawane, V. P. Chavan, M. S. Shingare,
B. K. Karale, Indian J. Heterocycl. Chem. 2002, 12, 65–66; c)
B. K. Karale, C. H. Gill, M. S. Shingare, Indian J. Heterocycl.
Chem. 2003, 12, 267–270.
N-(4-Bromobenzyl)quinidinium Bromide (Cat 3): Yield: 62%, m.p.
229–232 °C. [α]D = +164.2 (c = 1.0, MeOH). 1H NMR: δ = 0.9 (m,
1 H, one of 7-H), 1.7–1.9 (m, 2 H, 4-H, 5-H), 2.2–2.4 (m, 2 H, 3-
H, 1 H of 7-H), 2.8 (m, 1 H of 6-H), 3.3 (m, 1 H of 2-H), 3.7 (s, 3
H, 6Ј-OMe), 4.2, 4.3, 4.5 (3ϫm, 2ϫ1 H, 6-H, 8-H, 1 H of 2-H),
5.2 (d, 3JH,H = 16.7 Hz, 1 H, =CH2, Htrans), 5.3 (d, 3JH,H = 9.6 Hz,
[9] V. L. M. Silva, A. M. S. Silva, D. C. G. A. Pinto, J. A. S. Cava-
leiro, T. Patonay, Synlett 2004, 2717–2720.
[10] For reviews see: a) A. Lévai, W. Adam, J. Halász, C. Nemes,
T. Patonay, G. Tóth, Khim. Get. Soedin. 1995, 1345–1349; b)
T. Patonay, W. Adam, J. Halász, A. Lévai, C. Nemes, G. Tóth
in Flavonoids and Bioflavonoids 1995 Proceedings; (Eds: S.
Antus, M. Gábor, K. Vetschera), Akadémiai Kiadó, Budapest,
1996, pp. 167–176. Other selected papers: c) T. Patonay, A.
3
1 H, =CH2, Hcis), 5.6 (d, JH,H = 11.4 Hz, 9-H), 5.8–5.9 (m, 2 H,
3
=CH, 9-OH), 6.4 (br. s, 1 H of CH2), 6.6 (d, JH,H = 4.8 Hz, 1 H
3
3
of CH2), 7.1 (d, JH,H = 9.2 Hz, 1 H, 7Ј-H), 7.4 (d, JH,H = 7.6 Hz,
2ЈЈ,6ЈЈ-H), 7.5–7.6 (m, 3 H, 5Ј-H, 3ЈЈ,5ЈЈ-H), 7.7 (br. s, 1 H, 3Ј-H),
3
7.8 (d, JH,H = 9.2 Hz, 1 H, 8Ј-H), 8.5 (br. s, 1 H, 2Ј-H) ppm.
Eur. J. Org. Chem. 2008, 1937–1946
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
1945

T. Patonay et al.
FULL PAPER
Lévai, C. Nemes, T. Timár, G. Tóth, W. Adam, J. Org. Chem. [20]
L. Gyuricza, A. Kiss-Szikszai, T. Patonay, unpublished results.
1996, 61, 5375–5383; d) W. Adam, J. Jeko˝, A. Lévai, Z. Majer,
C. Nemes, T. Patonay, L. Párkányi, P. Sebo˝k, Tetrahedron:
Asymmetry 1996, 7, 2437–2446; e) W. Adam, R. T. Fell, A.
Lévai, T. Patonay, K. Peters, A. Simon, G. Tóth, Tetrahedron:
Asymmetry 1998, 9, 1121–1124; f) A. Lévai, W. Adam, R. T.
Fell, R. Gessner, T. Patonay, A. Simon, G. Tóth, Tetrahedron
1998, 54, 13105–13114; g) A. Lévai, W. Adam, J. Jeko˝, T. Pa-
tonay, A. Székely, E. B. Vass, J. Heterocycl. Chem. 2000, 37,
1065–1069; h) T. Patonay, J. Jeko˝, A. Kiss-Szikszai, A. Lévai,
Monatsh. Chem. 2004, 135, 743–756; i) C. M. M. Santos,
A. M. S. Silva, J. A. S. Cavaleiro, A. Lévai, T. Patonay, Eur. J.
Org. Chem. 2007, 2877–2887.
[21]
[22]
[23]
[24]
[25]
[26]
W. Adam, L. Hadjiarapoglou, A. Lévai, Synthesis 1992, 436–
438.
A. Messeguer, C. Fusco, R. Curci, Tetrahedron 1993, 49, 6299–
6308.
W. Adam, J. Jeko˝, A. Lévai, C. Nemes, T. Patonay, P. Sebo˝k,
Tetrahedron Lett. 1995, 36, 3669–3672.
J. A. Donnelly, J. R. Keegan, K. Quigley, Tetrahedron 1980, 36,
1671–1680.
B. C. B. Bezuidenhoudt, E. V. Brandt, D. Ferreira, J. Chem.
Soc. Perkin Trans. 1 1987, 1081–1087.
M. G. Constantino, V. Lacerda, G. V. J. da Silva, J. Heterocycl.
Chem. 2003, 40, 369–371.
[11] C. M. M. Santos, A. M. S. Silva, J. A. S. Cavaleiro, T. Patonay,
A. Lévai, J. Heterocycl. Chem. 2006, 43, 1319–1326.
[12] H. Harnisch, Justus Liebigs Ann. Chem. 1972, 765, 8–14.
[13] A. Nohara, T. Umetani, Y. Sanno, Tetrahedron 1974, 30, 3553–
3561.
[14] J. Alderete, J. Belmar, M. Parra, C. Zúñiga, V. Jimenez, Liq.
Cryst. 2003, 30, 1319–1325.
[27] K. Jakka, J. Y. Liu, C. G. Zhao, Tetrahedron Lett. 2007, 48,
1395–1398.
[28] R. Bernini, E. Mincione, A. Coratti, G. Fabrizi, G. Battistuzzi,
Tetrahedron 2004, 60, 967–971.
[29] H.-O. Kalinowski, S. Berger, S. Braun, 13C NMR-Spektrosko-
pie, Thieme Verlag, Stuttgart, New York, 1984.
[15] C. O. Kappe, A. Stadler, Microwaves in Organic and Medicinal [30] A. Berkessel, H. Gröger, Asymmetric Organocatalysis, Wiley-
Chemistry, Wiley-VCH, Weinheim, 2005.
[16] W. Adam, J. Bialas, L. Hadjiarapoglou, Chem. Ber. 1991, 124,
2377.
[17] a) A. L. Baumstark, C. J. McCloskey, Tetrahedron Lett. 1987,
28, 3311–3314; b) A. L. Baumstark, P. C. Vasquez, J. Org.
Chem. 1988, 53, 3437–3439.
[18] For reviews, see: a) R. W. Murray, Chem. Rev. 1989, 89, 1187–
1201; b) W. Adam, A. K. Smerz, Bull. Soc. Chim. Belg. 1996,
105, 581–599; c) V. P. Kazakov, A. I. Voloshin, D. V. Kazakov,
Russ. Chem. Rev. 1999, 68, 253–286; d) W. Adam, C. R. Saha-
Möller, C.-G. Zhao, Org. React. 2002, 61, 219–516.
[19] a) W. Adam, W. Haas, B. B. Lohray, J. Am. Chem. Soc. 1991,
113, 6202–6208; b) W. Adam, D. Golsch, Chem. Ber. 1994, 127,
1111–1113; c) W. Adam, D. Golsch, F. C. Görth, Chem. Eur.
J. 1996, 2, 255–258.
VCH, Weinheim, 2005.
[31] a) R. Helder, J. C. Hummelen, R. W. P. M. Laane, J. S. Wiering,
H. Wynberg, Tetrahedron Lett. 1976, 17, 1831–1834; b) J. C.
Hummelen, H. Wynberg, Tetrahedron Lett. 1978, 19, 1089–
1092; c) H. Wynberg, B. Greijdanus, J. Chem. Soc., Chem.
Commun. 1978, 427–428; d) H. Wynberg, B. Marsman, J. Org.
Chem. 1980, 45, 158–161.
[32] a) S. Arai, H. Tsuge, T. Shioiri, Tetrahedron Lett. 1998, 39,
7563–7566; b) S. Arai, H. Tsuge, M. Oku, M. Miura, T. Shioiri,
Tetrahedron 2002, 58, 1623–1630; c) B. Lygo, P. G. Wainwright,
Tetrahedron Lett. 1998, 39, 1599–1602; d) B. Lygo, D. C. M.
To, Tetrahedron Lett. 2001, 42, 1343–1346.
[33] C. K. Ghosh, J. Indian Chem. Soc. 1978, 55, 52–55.
Received: November 15, 2007
Published Online: February 20, 2008
1946
www.eurjoc.org
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2008, 1937–1946