Circular dichroism spectra of trans-chalcone epoxides

Article abstract of DOI:10.1016/j.tetasy.2007.06.034

The electronic absorption and CD spectra of (-)-trans-chalcone epoxide and its derivatives with methyl and alkoxy substituents at the ortho-positions of the aromatic rings have been measured. The spectra have been assigned with help of the energies, oscillatory strengths, and rotatory strengths of the singlet transitions obtained from DFT calculations. The features of the CD spectra, indicative of the absolute configuration, are the carbonyl n-π^* band and two further strong bands assigned to the overlapping signals of π-π^* and n_epoxy-π^* excitations.

Full text of DOI:10.1016/j.tetasy.2007.06.034

Tetrahedron: Asymmetry 18 (2007) 1521–1528
Circular dichroism spectra of trans-chalcone epoxides
a
b
a,b,
c
c
*
´
´
´
´
´ ´ ´
Peter Bako and Attila Mako
Krisztina Pal, Mihaly Kallay, Miklos Kubinyi,
aInstitute of Structural Chemistry, Chemical Research Center, Hungarian Academy of Sciences, PO Box 17, 1525 Budapest, Hungary
bDepartment of Physical Chemistry, Budapest University of Technology and Economics, 1521 Budapest, Hungary
cDepartment of Organic Chemical Technology, Budapest University of Technology and Economics, 1521 Budapest, Hungary
Received 9 March 2007; revised 23 June 2007; accepted 28 June 2007
Abstract—The electronic absorption and CD spectra of (ꢀ)-trans-chalcone epoxide and its derivatives with methyl and alkoxy substi-
tuents at the ortho-positions of the aromatic rings have been measured. The spectra have been assigned with help of the energies,
oscillatory strengths, and rotatory strengths of the singlet transitions obtained from DFT calculations. The features of the CD spectra,
indicative of the absolute configuration, are the carbonyl n–p* band and two further strong bands assigned to the overlapping signals of
p–p* and nepoxy–p* excitations.
ꢀ 2007 Elsevier Ltd. All rights reserved.
1. Introduction
The catalytic epoxidation of chalcone, leading to trans-chal-
cone epoxide has been used many times for characteriz-
ing the enantioselectivity of various types of chiral
catalysts.1a–k In several cases, the scope of the studies was
extended to substituted chalcones.2a–f Chiral chalcone
epoxides are also of great importance as intermediates for
the synthesis of natural products and pharmaceuticals, pri-
marily enantiomeric flavonoid monomers.3a–e
OCH3
O
O
O
O
O
N
(CH2)3-OH
O
O
1
The absolute configuration of chalcone epoxide was
deduced by chemical correlation,4 and the absolute config-
urations of some derivatives were determined by single
crystal X-ray diffraction2d and CD spectroscopy.2d,f,3b,d
The assignment of the CD spectra of trans-chalcone epox-
ides has so far been restricted to the band belonging to the
n–p* transition of the carbonyl group. Herein, we under-
took the analysis of the CD spectra of trans-chalcone epox-
ide 3 and its substituted derivatives 3a–e (see Scheme 1),
involving the lower wavelength range of the spectra, where
the bands associated with the p–p* transitions of the phenyl
and benzoyl groups are expected. Our aim has been to
identify the features of the CD spectra, which are indicative
of the absolute configurations of such molecules.
catalyst 1
-BuOOH
O
H
O
t
O
1
Ar1
Ar2 20%aq.NaOH
toluene
∗
Ar
Ar2
∗
H
2a-e
3, 3a-e
3
Ar1 = Ar2 = Ph
1
2
,
Ar = 2-CH3-Ph Ar = Ph
2a, 3a
2b, 3b
2c, 3c
2d, 3d
2e, 3e
1
2
,
Ar = 2-CH3O-Ph Ar = Ph
1
2
,
Ar = 2-EtOCH2O-Ph Ar = Ph
1
2
,
Ar = 2-CH(CH3)2O-Ph Ar = Ph
1
2
,
Ar = Ph Ar = 2-CH3-Ph
*
Corresponding author. Tel.: +36 1 438 1120; fax: +36 1 438 1143;
e-mail: kubinyi@mail.bme.hu
Scheme 1. The enantioselective epoxidation of chalcones.
0957-4166/$ - see front matter ꢀ 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2007.06.034

1522
K. Pa´l et al. / Tetrahedron: Asymmetry 18 (2007) 1521–1528
The CD spectra of various chalcone epoxides with substit-
uents in the para-position of their aromatic rings have been
published in our previous papers.2d,f The present study
concerns, primarily the substituent effects on the CD spec-
trum of chalcone epoxide caused by substituents at the
ortho-positions of its aromatic rings.
ods for the enantioselective epoxidation of trans-chalcones
were reported in the literature,12a–c whereas 3c and 3d are
novel compounds.
The requisite trans-(E)-chalcones having a methyl- or
methoxy group 2a and 2b were obtained by base-catalyzed
condensation of benzaldehyde with 20-methyl acetophe-
none13 or 20-methoxy acetophenone,14 respectively. The
reaction of acetophenone with ortho-tolualdehyde15 gave
compound 2e. Preparation of the novel analogues substi-
tuted with an ethoxymethyl group (EtOCH2O) 2c and 2d
having an isopropyl group were performed in two steps
(Scheme 2).
To achieve a reliable assignment of the spectra, quantum
chemical calculations were carried out to yield the equilib-
rium geometries, and the characteristics of the electronic
absorption and CD spectra. Whereas the calculations of
molecular geometries and absorption spectra are nowadays
well established, the computation of chiroptical spectra still
remains a difficult task. In recent years, significant progress
has been made in this field. Currently, implementations are
available at the semi-empirical level,5 for the ab initio con-
figuration interaction singles (CIS) and random phase
approximation (RPA) methods,6a,b the multireference
configuration interaction (MRCI),7a–c coupled cluster
(CC),8a–d and time-dependent density functional theory
(TD-DFT)9a–f approaches. Very recently, the inclusion of
vibrational effects in the calculation of CD spectra has been
considered and found to be vital in certain cases.10 It
has also been demonstrated that the vibronic coupling
can have additional, unusually strong effects on the CD
spectrum.11
20-Hydroxyacetophenone 4 was treated with chloromethyl
ethyl ether in a mixture of aq potassium hydroxide and
dichloromethane in the presence of tricaprylylmethyl
ammonium chloride3b to give compound 5c after column
chromatography with a yield of 47%. We obtained 20-iso-
propoxyacetophenone 5d in the reaction of compound 4
with isopropyl bromide (K2CO3, KI) in acetone16 with a
yield of 32%. The condensation of the substituted aceto-
phenones 5c and 5d with benzaldehyde gave chalcone
derivatives 2c (67%) and 2d (59%), respectively.
The epoxidation of chalcones with tert-butylhydroperoxide
(TBHP, 2 equiv) was carried out in a liquid–liquid two-
phase system in toluene, employing 20% aq NaOH
(3.5 equiv) as the base and 7 mol % of chiral crown catalyst
1 at a temperature of 2–5 ꢁC (Scheme 1). After the usual
work-up procedure, the product was isolated by prepara-
tive TLC. The asymmetric induction, expressed in terms
of the enantiomeric excess (ee), was monitored by 1H
NMR analysis using (+)-Eu(hfc)3 as a chiral shift reagent.
The trans-epoxyketones 3a–e were formed in all experi-
ments with excesses of the enantiomers with negative spe-
cific rotations. Table 1 summarizes the results obtained
2. Results and discussion
2.1. Synthesis of chalcone epoxides
The chiral trans-epoxyketones 3a–e were synthesized by the
enantioselective epoxidation of the corresponding trans-
chalcones 2a–e with tert-butylhydroperoxide using a phase
transfer catalyst, the chiral crown ether 1,2d (Scheme 1).
The preparations of 3a, 3b, and 3e using alternative meth-
O
OH
O
O
O
R
X
R
O
benzaldehyde
R
CH3
EtOH - aq. NaOH
CH3
aq. KOH
or
K2CO3
5
2c
2d
4
5c R = CH3CH2OCH2, X = Cl
5d R = CH(CH3)2, X = Br
Scheme 2.
Table 1. Epoxidation of substituted chalcones by t-BuOOH in the presence of catalyst 1 at 2–5 ꢁC
Ar1
Ar2
Epoxides
Time (h)
Yielda (%)
[a]D
eec (%)
b
Chalcones
2a
2b
2c
2d
2e
2-CH3–Ph
Ph
Ph
Ph
Ph
3a
3b
3c
3d
3e
4
8
8
12
4
52
49
46
53
55
ꢀ166.9
ꢀ98.5
ꢀ102.3
ꢀ131
71
83
70
79
76
2-CH3O–Ph
2-EtOCH2O–Ph
2-CH(CH3)2O–Ph
Ph
2-CH3–Ph
ꢀ75.7
a Based on isolation by preparative TLC.
b In CH2Cl2 at 22 ꢁC.
c Determined by 1H NMR spectroscopy in the presence of Eu(hfc)3 as a chiral shift reagent.

K. Pa´l et al. / Tetrahedron: Asymmetry 18 (2007) 1521–1528
1523
with the differently substituted ketones. As can be seen, the
20
15
10
5
0.24
0.18
0.12
0.06
0.00
yields are between 46% and 55%, the enantioselectivities
are significant (70–83% ee) and do not depend much on
the substituent on the aromatic ring.
a
2.2. Quantum chemical calculations
0
In order to reveal the effect of substitution on the CD spec-
tra, quantum chemical calculations have been performed
for (ꢀ)-3 and for two methyl and one methoxy derivatives,
3a, 3b, and 3e.
6
4
b
2
First, a conformational analysis was carried out for 3 based
on molecular mechanics calculations employing the
MMFF94 force field17 and simulated annealing algorithm.
Molecular mechanics calculations were carried out by the
SPARTAN’02 package.18 The analysis concluded that two
low-lying conformers existed. In the case of the lower-
energy conformer, the phenyl rings are approximately at a
right angle to one another, while they are roughly coplanar
for the other conformer. In order to determine the accurate
energy difference between the two conformers, geometry
optimizations were performed at the second-order Møl-
ler–Plesset (MP2) level using the resolution of identity
approximation (RI)19 and the TZPP basis set.20 The MP2
calculations were performed by the TURBOMOLE package.21
The results of the MP2 calculations suggest that the first
conformer is about 6 kJ/mol more stable than the other
one, which means that about 90% of the molecules are
twisted at room temperature. As a result the calculations
were restricted to the twisted form of the compounds.
The molecular geometries for the lowest-energy conformers
of the substituted derivatives have been optimized with the
aid of density functional theory (DFT) using the Becke 3-
parameter-Lee–Yang–Parr (B3LYP) functional22a,b and
Pople’s 6-311++G**-basis set.23
0
-2
-4
25
20
15
10
5
60
50
40
30
20
10
0
c
0
-10
-20
-5
-10
200
250
300
350
400
wavelength [nm]
Figure 1. Experimental and calculated spectra of trans-chalcone epoxide
(ꢀ)-3: (a) UV absorption spectrum and calculated oscillator strengths, (b)
experimental CD spectrum, (c) calculated rotatory powers and CD
spectrum.
30000
25000
After the geometry optimization, the absorption and CD
spectra of the compounds have been calculated with a
time-dependent DFT (TD-DFT) method24 using the above
functional and basis set. The rotatory strengths have been
calculated in the velocity gauge, which guarantees the
gauge origin independence of the calculated rotatory
strengths. For the treatment of the solvent effects, in a fur-
ther calculation the polarized continuum model (PCM)25a,b
method was used with ethanol as the solvent. The calcula-
tions have been carried out by the GAUSSIAN 03 suite of
quantum chemical programs.26
20000
(-)-3
15000
10000
5000
0
3e
3b
3d
3c
3a
250
200
300
wavelength [nm]
350
400
2.3. UV–vis absorption spectra
Figure 2. Absorption spectrum of trans-chalcone epoxide (ꢀ)-3 and its
derivatives 3a–e.
The UV–vis absorption and CD spectra of the unsubsti-
tuted compound 3 can be seen in Figure 1, where the
theoretically calculated electronic transitions are also
marked. The absorption spectrum of 3 is compared to
those of its derivatives 3a–e in Figure 2. The data of the ob-
served UV and CD spectra of 3, 3a, 3b, and 3e are listed in
Table 2, together with the wavelengths, oscillator strengths,
and rotatory strengths obtained in the quantum chemical
calculations for the isolated molecules. The calculations
carried out with the PCM method indicated that the sol-
vent effects are insignificant, for example, the theoretically
estimated solvent shifts fell between 1 and 15 nm.
2.3.1. Spectrum of trans-chalcone epoxide 3. The spectrum
of 3 (see Fig. 1a) can be assigned with help of the calculated
molecular orbitals, which are displayed in Figure 3 and
of the TD-DFT vector coefficients characterizing the

1524
K. Pa´l et al. / Tetrahedron: Asymmetry 18 (2007) 1521–1528
Table 2. The data of the observed UV and CD spectra of 3, 3a, 3b, and 3e,
together with the wavelengths, oscillator strengths and rotatory strengths
obtained in the quantum chemical calculations
Compound
Observed
CD spectra
kmax [nm]
Calculated
UV spectra
kmax [nm]
Electronic transitions
k [nm] (osc. strength)
(e [Mꢀ1 cmꢀ1]) (De [Mꢀ1 cmꢀ1]) {rot. strength}
3
330 (600)
290 sh
275 sh
324 (ꢀ2.007)
347 (0.012) {ꢀ15.7}
290 (0.165) {+6.8}
273 (0.003) {+3.3}
272 (0.018) {ꢀ4.2}
250 (0.239) {+7.9}
249 (0.021) {ꢀ11.7}
258 (ꢀ4.229)
250 (12,900)
203 (20,590)
235 (+5.425)
3a
3b
3e
335 sh (600)
295 sh (2000)
323 (ꢀ2.190)
346 (0.010) {ꢀ20.7}
285 (0.208) {ꢀ9.1}
281 (0.017) {+0.9}
266 (0.002) {ꢀ0.7}
250 (0.171) {+29.5}
244 (0.009) {ꢀ12.1}
257 (ꢀ2.990)
250 (12,500)
205 (25,200)
234 (+4.035)
360 sh
313 (4460)
270 sh
349 (0.014) {ꢀ17.9}
308 (0.150) {ꢀ9.8}
276 (0.112) {ꢀ2.7}
260 (0.002) {ꢀ1.1}
248 (0.075) {+23.5}
240 (0.008) {ꢀ7.8}
308 (ꢀ4.402)
265 (ꢀ1.877)
255 (11,500)
210 (24,060)
237 (+8.021)
332 (700)
290 sh
282 (2790)
270 sh
324 (ꢀ1.841)
279 (+1.944)
259 (ꢀ1.687)
239 (+4.151)
345 (0.002) {ꢀ4.2}
298 (0.018) {ꢀ2.4}
282 (0.023) {+3.6}
271 (0.017) {+3.6}
258 (0.008) {ꢀ12.5}
250 (0.319) {ꢀ5.6}
Figure 3. Molecular orbitals involved in the six lowest-energy transitions
of compound 3. The transitions are: (1) (HOMO)!(LUMO), (2)
(HOMOꢀ2)!(LUMO), (3) (HOMOꢀ1)!(LUMO), (4) (HOMOꢀ3)!
(LUMO), (5) (HOMOꢀ4)!(LUMO), and (6) (HOMOꢀ5)!(LUMO).
250 (14,020)
204 (24,060)
contributions of the individual single electron promotions
to the excited-state wave functions (not given here).
der at 290 nm corresponds to another combination of the
HOMO!LUMO and HOMOꢀ2!LUMO excitations.
It is a common feature of the lowest-energy transitions that
they all involve the LUMO as the unoccupied orbital, the
excitations to LUMO+1 start at relatively high energies.
The LUMO can be considered as the p* orbital of the car-
The strong band at 250 nm probably covers at least four
electronic transitions. The weak shoulder at around
275 nm can be assigned to the 3rd and 4th transitions in
Table 2 (in order of increasing energy), which are nearly
degenerate and have pPh ! pꢁCO character. For the 3rd
transition the HOMOꢀ1!LUMO excitation is predomi-
nant, while in the other the HOMOꢀ3!LUMO is pre-
dominant. The HOMOꢀ1 and HOMOꢀ3 are p orbitals
of the two benzene rings, by shape they are the analogues
of the HOMOs of toluene27 and benzaldehyde,28 respec-
tively. The peak at 250 nm also seems to be associated with
two closely lying transitions. One of them, the 5th in Table
2, is dominated by the HOMOꢀ4!LUMO, the other (6th
in Table 2) by the HOMOꢀ5!LUMO single electron pro-
motion. The HOMOꢀ4 is a p orbital of the Ph1 unit, while
HOMOꢀ5 is an n-orbital of the epoxy oxygen, O2, thus
the 5th transition is of pPh1 ! pꢁCO character, the 6th one
is a nO2 ! pꢁCO type charge transfer (CT) transition.
bonyl moiety, pꢁCO
.
The weak band at 330 nm belongs to the lowest-energy
transition, which is a mixture of the HOMO!LUMO
and the HOMOꢀ2!LUMO single electron promotions.
Empirically this band would be described as a carbonyl
n!p* transition. In fact, by the calculations none of the
occupied MO-s can be visualized as a ‘clear’ n-orbital of
the carbonyl oxygen, O1. In the HOMO the nO1 orbitals
are combined with the p orbitals of Ph2, the phenyl group
attached to the epoxy ring, in the HOMOꢀ2 they are com-
bined with the p orbitals of Ph1, the phenyl group of the
benzoyl moiety, thus this transition has
a mixed
nO1 ! pꢁCO, pPh1 ! pCꢁ O, pPh2 ! pCꢁ O character. The shoul-

K. Pa´l et al. / Tetrahedron: Asymmetry 18 (2007) 1521–1528
1525
2.3.2. Substituent effects. As can be seen in Figure 2, the
15
10
5
experimental spectra of the methyl derivatives 3a and 3e
show a close resemblance to the spectrum of the unsubsti-
tuted compound 3, whereas the spectra of the alkoxy deriv-
atives 3b–d differ markedly: the two strong bands of 3 shift
to lower wavelengths and a third intense band appears
around 320 nm. The analysis of the theoretical results leads
to a plausible explanation.
3e
3b
0
-5
3c
Although the effect of methyl-substitution on the experi-
mental spectrum is modest, the assignment of the spectrum
is somewhat different. The methyl substituent in the Ph2
group induces a shift of the transition corresponding to
the 3rd ðpPh2 ! pꢁCOÞ one of 3 to lower energies. Hence,
the shoulder at 290 nm is assigned to the 3rd transition
of 3, while the shoulders at 282 and 270 nm likely corre-
spond to the 2nd and 4th transitions of the unsubstituted
compound, respectively. In addition, the methyl substitu-
tion results in a change in the energy of the nO2 ! pꢁCO tran-
sition (6th of 3): it shifts to the higher energies, thus the 5th
and 6th transitions of 3 are reversed and their quasi-degen-
eracy is broken.
-10
-15
-20
3a
(-)-3
3d
220
240
260
280
300
320
340
360
380
400
wavelength [nm]
Figure 4. CD-spectra of trans-chalcone epoxide (ꢀ)-3 and its substituted
derivatives 3a–e. The spectra are normalized to the same height at the
maximum of the highest energy band to facilitate comparison.
2.4.1. The signal of the carbonyl group. In the CD spec-
trum of (ꢀ)-3, the lowest-energy transition gives rise to a
negative Cotton effect around 320 nm. In case of saturated
ketones the sign of this n–p* carbonyl band correlates with
the absolute configuration according to the octant rule.30
For predicting the sign of the carbonyl band of unsaturated
ketones modified versions of the octant rule have been
proposed, such as the ‘helicity rule’ for a,b-unsaturated
ketones and the ‘extended octant rule’ for b,c-unsaturated
ones.31
The influence of the methoxy substituent is even more
pronounced. The HOMO, HOMOꢀ1, HOMOꢀ2, and
HOMOꢀ3 orbitals, which determine the low-energy part
of the spectrum, are strongly perturbed. The introduction
of the methoxy substituent into the Ph1 group is accompa-
nied by a decrease in the energy of the pPh1 ! pꢁCO transi-
tion, which is the analogue of the 4th transition of 3.
Due to this shift, the above p!p* transition of 3b will be
the second in order of increasing energy and the quasi-
degeneracy of the 3rd and 4th transitions of 3 is again
lifted. The shift manifests in the appearance of a strong
peak at 313 nm corresponding to the 4th transition of 3.
Furthermore, the 6th transition of 3b shifts to lower ener-
gies, and thus the 5th and 6th transitions of this molecule
will be more separated.
To decide if the octant rule applies to the chalcone epoxide,
the octant projection diagram of the (2R,3S)-enantiomer
was prepared by rotating the calculated equilibrium struc-
ture into the appropriate position. The diagram is shown in
Figure 5. The octant rule for such an arrangement predicts
a negative Cotton effect, since the chiral disturbance of the
carbonyl group arises primarily from the atoms lying in the
2.4. Stereostructures and CD spectra
The experimental CD spectrum of (ꢀ)-3, which is shown in
Figure 1b, proves that (ꢀ)-3 is identical to the (2R,3S)-
enantiomer since this spectrum agrees with the one
obtained for this isomer by Marsman and Wynberg who
determined the absolute configuration by chemical correla-
tion.4 The calculated CD spectrum of (ꢀ)-3 obtained from
the theoretically computed wavelengths and rotatory
strengths in Table 2, presuming Gaussian band shapes of
widths r = 0.2 eV,29 can be seen in Figure 1c. The observed
spectra of the substituted compounds are shown in
Figure 4.
The source of the chirality in case of trans-chalcone epox-
ides is the strained epoxide ring that involves two stereo-
centers. Since the epoxide ring is not a chromophoric
unit, the Cotton effects in the CD spectra of chalcone epox-
ides originate from inherently symmetric chromophores
that are asymmetrically perturbed by these stereocenters.
These chromophore units are the carbonyl group and the
chirally fixed phenyl rings of the molecule.
Figure 5. Octant projection diagram for the lowest-energy conformer of
trans-chalcone epoxide (ꢀ)-3.

1526
K. Pa´l et al. / Tetrahedron: Asymmetry 18 (2007) 1521–1528
lower back left octant. Consequently, the negative sign of
the carbonyl band in the CD spectrum of (2R,3S)-3 is in
accordance with the octant rule. Thus, the conjugation
between the carbonyl group and the phenyl ring, which
are quasi-coplanar in our molecule, leads to a red shift of
the n–p* carbonyl band but not to the reversion of its sign.
be assigned to the 3rd and 4th, the negative band around
260 nm to the 5th and 6th transitions.
3. Conclusion
There are three main features in the CD spectrum of the
parent compound, a carbonyl band around 320 nm, and
two further strong bands, at 260 nm and 235 nm, which
can be assigned to the overlapping signals of several tran-
sitions. The analogous bands appear in the spectra of deriv-
atives with substituents in the ortho and, as reported in our
previous papers, in para-positions of the aromatic rings,
facilitating a simple method for the determination of their
absolute configuration. The theoretical calculations with
the TD-DFT method led to a plausible assignment of the
UV and CD spectra.
Since the rotatory strengths of the (2R,3S)-isomer have
been calculated, the absolute configuration can also be
obtained by a direct comparison of the signs of the
observed and calculated carbonyl signals. The calculated
negative rotatory strength confirms the (2R,3S) configura-
tion of the stereocenters in (ꢀ)-3.
Comparing the k >300 nm ranges of the CD spectra of the
substituted derivatives to that of the unsubstituted com-
pound, noticeable differences can be seen in the spectra
of the alkoxy derivatives 3b–d. These spectra contain a
band at ꢂ310 nm with a shoulder around 330 nm. The neg-
ative signs of these features are in accordance with the sign
of the calculated rotatory strengths of the first and second
transitions of 3b. Taking into account the descriptions of
the two transitions, the shoulder may be assigned as the
‘carbonyl signal’.
4. Experimental
4.1. Instrumentation
Melting points were determined using a Buchi 510 appara-
¨
tus and are uncorrected. The optical rotations were mea-
sured on a Perkin–Elmer 241 polarimeter at 22 ꢁC, while
the IR spectra were recorded on a Perkin–Elmer 237 spec-
trophotometer. NMR spectra were obtained on a Brucker
300 and a Brucker DRX-500 instrument in CDC13. Mass
spectra were obtained on a Varian MAT312 instrument.
Analytical and preparative thin layer chromatography
was performed on silica gel plates (60 GF-254, Merck),
while column chromatography was carried out using 70–
230 mesh silica gel (Merck). The shift reagent was Eu(hfc)3
(Aldrich Chem. Co.).
2.4.2. The CD-spectra between 220 and 300 nm. In the CD
spectrum of (ꢀ)-3, there is a positive band at 235 nm and a
negative one at 259 nm—the latter with two shoulders—in
the wavelength range of the strong UV absorption band
around 250 nm. They resemble an exciton couplet,32 while
the inflection point between them almost coincides with the
maximum of the UV band. If it is a couplet its appearance
can be due to the coupling between two singlet transi-
tions—the 5th and 6th in Table 2, which was described
qualitatively as a p!p* excitation of the benzoyl moiety,
and as a CT type n!p* transition with the involvement
of the epoxy and carbonyl unit. It is more likely, however,
that the negative band is associated with two pairs of
closely lying transitions—3rd and 4th, 5th and 6th—in
which the component with the negative rotating power is
dominant. In the lower wavelength range of the spectrum,
the density of transitions increases substantially, making
the assignment of the strong positive band difficult. The
calculations suggest that in this feature the contribution
of the 12th transition is dominant. This transition, which
can be described as a mixture of pPh1 ! pꢁPh1 and
pPh1 ! pꢁPh2 excitations, has a very high positive rotating
power.
UV–vis absorption spectra of chalcone epoxides were re-
corded on an Agilent 8453 diode array spectrometer, their
CD spectra were recorded on a Jasco J-810 spectropolari-
meter. The solvent was of HPLC grade ethanol from
Merck.
4.2. Preparation of alkoxymethyl acetophenon, 5c
A
solution of the 2-hydroxyacetophenone 4 (7.0 g,
51 mmol) in 15% (m/v) aq KOH (70 ml) was stirred for
2 h. CH2Cl2 (70 ml) and Aliquat 336 phase transfer catalyst
(5.25 g, 15.6 mmol) were added and stirring was continued
for 10 min. Chloromethyl ethyl ether (6.53 g, 69 mmol) was
added dropwise and the mixture stirred for 50 min at ambi-
ent temperatures. Removal of the organic phase and
extraction of the aqueous layer with CH2Cl2 (2 · 20 ml)
gave the crude product after drying over Na2SO4 and evap-
oration of the solvent. Flash chromatography with CHCl3
eluent yielded 4.65 g of the pure product 5c as an oil (47%).
1H NMR (500 MHz, CDCl3) d ppm: 1.25 (t, 3H); 2.63 (s,
3H); 3.76 (q, 2H); 5.33 (s, 2H); 7.04 (t, 1H); 7.21 (d, 1H);
7.44 (t, 1H); 7.70 (d, 1H). 13C NMR (300 MHz, CDCl3)
d ppm: 15.22; 31.90; 64.92; 93.32; 115.03; 121.70; 129.21;
130.27; 133.61; 156.70; 200.06. HRMS calcd for
C11H14O3 (M+): 194.0943, found: 194.0955.
In the spectra of 3a–d, derivatives with ortho-substituted
benzoyl rings, the negative bands around 260 nm are weak-
er than in the spectrum of the parent compound. Calcula-
tions predict a positive band for 3a and 3b in the position
of the 260 nm negative one of (ꢀ)-3. The experimental
spectra do not show such a dramatic change, but the
respective negative bands are much weaker than in the
spectrum of the parent compound.
The observed and calculated spectra of 3e, the derivative
with a methyl group in the o-position of the Ph2 ring, are
in good agreement. The positive band around 280 nm can

K. Pa´l et al. / Tetrahedron: Asymmetry 18 (2007) 1521–1528
1527
4.3. Preparation of chalcones
1H); 6.93 (d, 1H); 7.05 (t, 1H); 7.36–7.40 (m, 5H); 7.52
(t, 1H); 7.83 (d, 1H). HRMS calcd for C16H14O3 (M+):
254.0943, found: 254.0940.
To a solution of the appropriate acetophenone (36 mmol)
in ethanol (10 ml) was added a solution of NaOH
(46 mmol) in water (16 ml) and the mixture was stirred at
room temperature for 30–40 min. Excess benzaldehyde
(37.8 mmol in 10 ml EtOH) was added dropwise and the
reaction was monitored by TLC (hexane–EtOAc 10:1).
After the disappearance of the acetophenone (4–36 h),
water (40 ml) was added and the products extracted with
CHCl3 (2 · 50 ml). The combined extracts were washed
with aq HCl (30 ml) and water (2 · 50 ml). Drying of the
extracts over Na2SO4 followed by evaporation and flash
column chromatography, gave the pure chalcones as an
oil, 2a (90%),1f 2b (68%),1g 2c (67%) 2d (59%), 2e
(65%).1c The data are given only for the novel analogues,
2c and 2d.
4.4.3. (2R,3S)-2,3-Epoxy-1-(2-ethoxymethyloxyphenyl)-3-
phenylpropan-1-one, 3c. Yield: 46% (white crystals); mp:
22
1
81–82 ꢁC; ½aꢃD ¼ ꢀ102:3 (c 1, CH2Cl2); 70% ee; H NMR
(500 MHz, CDCl3) d ppm: 1.03 (t, 3H); 3.30 (q, 2H); 4.01
(d, J = 2 Hz, 1H); 4.30 (d, J = 1.5 Hz, 1H); 4.90 (d, 1H);
4.97 (d, 1H); 7.09 (t, 1H); 7.19 (d, 1H); 7.35–7.41 (m,
5H); 7.49 (t, 1H); 7.81 (d, 1H). HRMS calcd for
C18H18O4 (M+): 298.1205, found: 298.1209.
4.4.4. (2R,3S)-2,3-Epoxy-1-(2-isopropoxyphenyl)-3-phenyl-
propan-1-one, 3d. Yield: 53% (yellow crystals); mp: 116–
22
118 ꢁC ; ½aꢃD ¼ ꢀ131 (c 1, CH2Cl2); 79% ee; 1H NMR
(500 MHz, CDCl3)
d ppm: 0.93 (t, 6H); 4.01 (d,
J = 1.5 Hz, 1H); 4.44 (d, J = 1.5 Hz, 1H); 4.57 (m, 1H);
6.93 (d, 1H); 7.01 (t, 1H); 7.33–7.40 (m, 5H); 7.48 (t,
1H); 7.85 (d, 1H). HRMS calcd for C18H18O3 (M+):
282.1256, found: 282.1260.
4.3.1. 20-O-Ethoxymethylchalcone, 2c. Yield: 67% (yellow
oil); 1H NMR (500 MHz, CDCl3) d ppm: 1.20 (t, 3H); 3.71
(q, 2H); 5.28 (s, 2H); 7.08 (t, 1H); 7.23 (d, 1H); 7.32–7.47
(m, 5H); 7.57–7.62 (m, 4H). 13C NMR (500 MHz, CDCl3)
d ppm: 15.25; 64.91; 93.77; 115.51; 122.05; 127.34; 128.54
(2·); 129.11 (2·); 130.25; 130.42; 130.51; 132.81; 135.24;
143.71; 155.88; 193.50. HRMS calcd for C18H18O3 (M+):
282.1256, found: 282.1264.
4.4.5. (2R,3S)-2,3-Epoxy-1-phenyl-3-(2-tolyl)-propan-1-one,
22
3e. Yield: 55% (yellow oil); ½aꢃD ¼ ꢀ75:7 (c 1, CH2Cl2);
76% ee; 1H NMR (500 MHz, CDCl3) d ppm: 2.37 (s,
3H); 4.22 (d, J = 1.5 Hz, 2H); 7.20 (t, 1H); 7.26–7.28 (m,
2H); 7.34 (t, 1H); 7.51 (t, 2H); 7.64 (t, 1H); 8.05 (d, 1H).
HRMS calcd for C16H14O2 (M+): 238.0994, found:
238.0983.
4.3.2. 20-O-Isopropylchalcone, 2d. Yield: 59% (yellow oil);
1H NMR (300 MHz, CDCl3) d ppm: 1.35 (d, 6H); 3.71 (q,
2H); 4.64 (m, 1H); 6.97–7.04 (m, 2H); 7.38–7.67 (m, 9H).
13C NMR (300 MHz, CDCl3) d ppm: 22.14; 29.70; 71.18;
114.31; 120.62; 127.34; 128.25 (2·); 128.88 (2·); 130.06;
130.47; 130.72; 132.80; 135.31; 142.25; 155.65; 193.05.
HRMS calcd for C18H18O2 (M+): 266.1307, found:
266.1302.
Acknowledgment
This work was supported by Grants T42546, T42514, and
D 48583 from the Hungarian Research Foundation. The
authors are grateful to Dr. Thorsten Metzroth (University
of Mainz) for his help in the conformational analysis and
MP2 calculations.
4.4. Epoxidation of chalcones
A solution of chalcone (1.44 mmol) and the chiral catalyst
1 (0.1 mmol) in toluene (3 ml) containing sodium hydrox-
ide (1 ml 20% aq) was treated with 50% tert-butylhydroper-
oxide in decane (0.5 ml, 2.88 mmol) and the mixture stirred
at 0–4 ꢁC. After a reaction time of 4–12 h, a new portion of
toluene (7 ml) and water (10 ml) were added. The organic
phase was washed twice with 10% aq hydrochloric acid
(10 ml) and then with (10 ml) water. The organic phase
was dried over Na2CO3. The crude product obtained after
evaporating the solvent was purified by preparative TLC
(silica gel, hexane–ethylacetate, 10:1, eluant) to give epoxy
ketones 3a–e in pure form.
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