Asymmetric epoxidation of trans-chalcones organocatalyzed by β-amino alcohols

Article abstract of DOI:10.1002/ejoc.200800140

Cyclic and acyclic β-amino alcohols were examined as organocatalysts in the epoxidation of trans-chalcones with tert-butyl hydroperoxide as the oxidant. Primary, secondary, and tertiary β-amino alcohols are able to promote the reaction with variable activity and level of asymmetric induction. Subtle modifications to the structures of simple primary β-amino alcohol strongly influenced their efficiency in the epoxidation. They are promising catalysts that afford trans-chalcone epoxides in up to 52%ee at room temperature. Wiley-VCH Verlag GmbH & Co. KGaA, 2008.

Full text of DOI:10.1002/ejoc.200800140

FULL PAPER
DOI: 10.1002/ejoc.200800140
Asymmetric Epoxidation of trans-Chalcones Organocatalyzed by β-Amino
Alcohols
Alessio Russo[a] and Alessandra Lattanzi*[a]
Keywords: Asymmetric synthesis / Epoxidation / Organocatalysis / Amino alcohols
Cyclic and acyclic β-amino alcohols were examined as or- alcohol strongly influenced their efficiency in the epoxid-
ganocatalysts in the epoxidation of trans-chalcones with tert-
butyl hydroperoxide as the oxidant. Primary, secondary, and
tertiary β-amino alcohols are able to promote the reaction
with variable activity and level of asymmetric induction. Sub-
tle modifications to the structures of simple primary β-amino
ation. They are promising catalysts that afford trans-chalcone
epoxides in up to 52%ee at room temperature.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2008)
O-protected diaryl-2-pyrrolidinemethanols in the presence
of aqueous H2O2 as the oxidant.[12] At the same time, we
found that diaryl-2-pyrrolidinemethanols 2, which are read-
ily accessible from -proline, catalyzed the asymmetric
epoxidation of α,β-enones by using tert-butyl hydroperoxide
(TBHP) as the oxidant (Scheme 1).[13] The epoxy ketones
were isolated in good yields and high ee values (up to
94%ee). Improvements in the activity and the enantio-
selectivity of the original promoter α,α-diphenyl--prolinol
(2a) were achieved by employing modified derivatives. In-
deed, higher conversions and ee values were achieved by
using electron-rich phenyl-substituted compounds 2[13b,13c]
at a significantly reduced loading (10 mol-%) with respect
to commercially available 2a employed at 30 mol-% load-
ing.[13a]
Introduction
The development of new methodologies, characterized
by operational simplicity and the use of easily available cat-
alysts, is the main target of modern organic synthesis.
Asymmetric organocatalysis offers most of these advan-
tages, as metal-free and environmentally friendly conditions
have been developed for many transformations by using
small organic molecules as chiral promoters.[1] Because of
the great synthetic versatility and the pharmaceutical im-
portance of enantiomerically enriched epoxides, different
approaches have been disclosed to access these compounds.
The asymmetric epoxidation of alkenes has been the privi-
leged route to epoxides.[2] Most of the methods are based
on metal complexes and chiral ligands such as the well-
known Ti–tartrate-mediated epoxidation of allylic
alcohols[3] and the chiral manganese salen catalyzed epoxid-
ation of cis alkenes.[4] Organocatalyzed enantioselective
epoxidation of unfunctionalized alkenes with oxazirid-
ines,[5] chiral dioxiranes,[6] oxaziridinium salts,[7] and
amines[8] were also reported. The Juliá–Colonna reaction,
which was discovered more than two decades ago, can be
considered one of the most efficient ways to epoxidize elec-
tron-poor alkenes.[9] Over the years, this reaction, which is
promoted by homo-oligopeptides, has been intensively in-
vestigated by different groups and significant improvements
have been reached in terms of practicality[10] as well as in
the understanding of the mechanism of asymmetric induc-
tion.[11] Recently, notable results have been achieved in the
asymmetric epoxidation of α,β-unsaturated aldehydes, a
challenging transformation, which was promoted by simple
Scheme 1. Diaryl-2-pyrrolidinmethanol-catalyzed asymmetric
epoxidations of α,β-enones.
Although modifications at the phenyl ring of 2a led to
appreciable results in the epoxidation, the β-amino alcohol
framework deserved a more in-depth investigation. Here,
we report the study on the employment of easily available
and differently substituted primary, secondary, and tertiary
cyclic and acyclic β-amino alcohols as organocatalysts in
the asymmetric epoxidation of chalcones. This investigation
helped to shed more light on the structural requirements of
[a] Dipartimento di Chimica, Università di Salerno,
Via Ponte don Melillo, 84084, Fisciano, Italy
Fax: +39-089-969603
E-mail: lattanzi@unisa.it
Supporting information for this article is available on the
WWW under http://www.eurjoc.org/ or from the author.
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A. Russo, A. Lattanzi
FULL PAPER
the β-amino alcohol that is important for the catalysis, and trans-chalcones (Table 2). In all the examples,[15] catalyst 4a
the results provide clues for further developments and proved to be rather less effective than 2b, but the enantio-
mechanistic interpretation of this oxidative system.
selectivity was marginally decreased.
Table 2. Epoxidation of 1 with catalyst 4a and TBHP.[a]
Results and Discussion
In our previous studies, organocatalyst 2b was identified
as the most effective promoter (Figure 1).[13c] The aromatic
substitution pattern was maintained and the aliphatic ring
was modified for the synthesis of cyclic compounds 4a and
5a, which were obtained as reported in the literature,[13c,14]
starting from the corresponding commercially available -
amino acids.
Entry
R
R1
Time [h] Yield 3 [%][b] ee 3 [%][c]
1
2
3
4
5
6
Ph
4-BrC6H4
3-CH3C6H4 Ph
Ph
Ph
Ph
Ph
Ph
112
165
142
144
141
117
33 (93)
45 (98)
46 (87)
21 (65)
22 (80)
10 (70)[d]
85 (89)
82 (86)
86 (89)
85 (86)
82 (86)
60 (69)[d]
4-CNC6H4
4-CH3C6H4
2-ClC6H4
[a] Molar ratios: 1/4a/TBHP, 1:0.10:1.4. [b] Isolated products after
flash chromatography. Yields in parenthesis refer to those reported
in ref.[13c] by using catalyst 2b. [c] Determined by HPLC analysis
on Chiralcel OD and Chiralpack AD columns. The ee values in
parentheses refer to those reported in ref.[13c] by using catalyst 2b.
Absolute configuration (αR,βS) was determined by comparison of
the HPLC retention times with those in the literature. [d] The reac-
tion was carried out by using catalyst 2b (15 mol-%).[13c]
Figure 1. Modified cyclic amino alcohols employed in the epoxid-
ation.
The ability to catalyze the epoxidation of 1a by a variety
of commercially available primary β-amino alcohols, and
among them, acyclic compounds structurally retaining the
The epoxidation of model compound trans-chalcone (1a; gem-diphenyl carbinol group, was then studied (Table 3).
R = R1 = Ph) was carried out by employing compounds 4a
and 5a under standard conditions[13c] (Table 1).
In order to compare the activity of the organocatalysts
with that of compound 2a, the reactions were carried out
by using 30 mol-% of the promoter. β-Amino alcohols hav-
ing one chiral center, respectively bearing the amino or the
hydroxy groups (Table 3, Entries 1 and 2), led to the forma-
tion of the epoxide in low yield and ee. The substitution at
the chiral carbon center binding the amino group played a
major role in controlling the asymmetric induction. When
two chiral centers were present in the amino alcohol
(Table 3, Entries 3–5), a sterically rigid scaffold as in cata-
lysts 9 and 10 is necessary to assure a beneficial effect in
the conversion and more importantly in the ee with respect
to compound 8. Moreover, trans-10 proved to be signifi-
cantly more enantioselective than cis-9. Acyclic catalysts
11a–d bearing the diphenyl carbinol group afforded
(αR,βS)-3a in low-to-modest yield and low ee, although a
moderate influence on the asymmetric induction was dis-
played by the substituent at the chiral center (Table 3, En-
tries 6–9). It is interesting to note that catalyst activity was
reduced in the absence of the hydroxy group as in the case
Table 1. Epoxidation of 1a with catalysts 2b, 4a, and 5a and
TBHP.[a]
Entry
Catalyst
Time [h]
Yield 3a [%][b] ee 3a [%][c]
1[d]
2
3
2b
4a
5a
110
112
118
93
33
48
89
85
75
[a] Molar ratios: 1a/catalyst/TBHP, 1:0.10:1.4. [b] Isolated products
after flash chromatography. [c] Determined by HPLC analysis on
Chiralcel OD column. Absolute configuration (αR,βS) was deter-
mined by comparison of the HPLC retention times with those in
the literature. [d] Yield and ee values as reported in ref.[13c]
.
Azetidinol derivative 4a afforded (αR,βS)-3a in low yield of compound 11e (Table 3, Entry 10), which was signifi-
but in fairly good enantioselectivity (Table 1, Entry 2). Six- cantly less active than catalyst 11a (Table 3, Entry 6). This
membered ring catalyst 5a proved to be more active than result confirmed the importance of the OH group in the
4a but significantly less enantioselective (Table 1, Entry 3). catalysis as previously observed for diaryl pyrrolidinemeth-
These results clearly showed that ring size is crucial for the anols.[13] Then, trifluoroacetic acid was added as a cocata-
epoxidation to proceed and the pyrrolidine ring ensured the lyst with the use of 11e, but the epoxidation did not proceed
highest conversion and asymmetric induction.
(Table 3, Entry 11). A similar result was achieved in the
Although less active compound, 4a yielded 3a in good presence of 15 mol-% of p-toluensulfonic acid (Table 3, En-
asymmetric induction (Table 1, Entry 2). Further experi- try 12). These findings suggest that even in the presence of
ments were then carried out to better ascertain the perform- a primary amine as a catalyst, the epoxidations of chalcones
ance of 4a with respect to 2b in the epoxidation of different do not seem to proceed through iminium formation,[16] as
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Asymmetric Epoxidation of trans-Chalcones
Table 3. Epoxidation of 1a with primary β-amino alcohols and
Table 4. Epoxidation of 1a with modified catalysts of type 11b and
TBHP.[a]
TBHP.[a]
[a] Molar ratios: 1a/catalyst/TBHP, 1:0.30:1.4. [b] Isolated products
after flash chromatography. [c] Determined by HPLC analysis on
Chiralcel OD column. Absolute configuration (αR,βS) was deter-
mined by comparison of the HPLC retention times with those in
the literature.
bearing p-tert-butyl groups, which was scarcely soluble in
the reaction mixture, had a comparable performance to un-
modified compound 11b (Table 4, Entry 4). It appears that
in the series of acyclic primary β-amino alcohols 12a–d,
which are structurally similar to secondary cyclic catalysts
2, the type of substitution at the phenyl ring remarkably
affected the level of enantiocontrol. Both meta and para
substituents seem to equally influence the asymmetric in-
duction, but in a less predictable way as previously observed
in modified catalyst of type 2.
[a] Molar ratios: 1a/catalyst/TBHP, 1:0.30:1.4. [b] Isolated products
after flash chromatography. [c] Determined by HPLC analysis on
Chiralcel OD column. Absolute configuration (αR,βS) was deter-
mined by comparison of the HPLC retention times with those in
the literature. [d] TFA (30 mol-%) was added. [e] p-Toluensulfonic
acid (15 mol-%) was added.
Some secondary β-amino alcohols were examined in the
epoxidation of 1a (Table 5). The introduction of a methyl
or a benzyl group in compound 13 and 14 was detrimental
reported for the epoxidation of enals organocatalyzed by for the activity and the enantioselectivity (Table 5, Entries 1
secondary amines[12,17] and anilines.[18,19] The most efficient and 2). Cycloesan N-benzylated catalyst 15, which is a γ-
catalyst 11b was then modified at the phenyl ring to study amino alcohol, was slightly more active and enantioselec-
the impact on the activity (Table 4).
tive than 13 and 14 (Table 5, Entry 3). It is important to
Promoter 12a bearing the previously optimized aromatic point out how acyclic secondary compounds 13 and 14 are
moiety, when used in the epoxidation, afforded the epoxide very poor catalysts relative to structurally similar cyclic sec-
in low yield but greatly enhanced ee (Table 4, Entry 1).[20] ondary α,α--diphenyl prolinol (2a; Table 5, Entry 4).
Compound 12b lacking the p-methoxy groups proved to be Moreover, their performance is significantly inferior to that
far more active, and the epoxide was isolated in satisfactory of parent primary amino alcohol 11b (Table 3, entry 7).
yield and improved ee relative to those of compound 11b Then, O-methylated catalyst 2c was employed in the epoxid-
(Table 4, Entry 2). Catalyst 12c having sterically hindered ation of 1a to afford the product in poor yield, but satisfac-
tert-butyl groups in the meta positions of the phenyl rings tory ee (Table 5, Entry 5).
led to a poor result (Table 4, Entry 3). Thus, the size of the
Finally, some tertiary β-amino alcohols were employed
substituents in the meta positions plays a relevant role in as catalysts in the epoxidation of 1a (Table 6). N-Methyl -
the control of the enantioselectivity. Finally, catalyst 12d pyrrolidinol (16) gave epoxide 3a in 17% yield and 7%ee
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A. Russo, A. Lattanzi
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Table 5. Epoxidation of 1a with secondary β-amino alcohols and
Upon analysis of the data in Tables 1–6, a picture
emerges in which the epoxidation of trans-chalcone can be
promoted with variable efficiency by primary, secondary,
and tertiary β-amino alcohols. In addition to these observa-
tions, epoxidation was prevented in the presence of a pri-
mary amine and an acid as cocatalyst (Table 3, Entries 11
and 12). These data further confirm and generalize our hy-
pothesis that the β-amino alcohol plays the role of a bifunc-
tional catalyst according to the catalytic cycle proposed in
Figure 2.
TBHP.[a]
[a] Molar ratios: 1/4a/TBHP, 1:0.30:1.4. [b] Isolated products after
flash chromatography. [c] Determined by HPLC analysis on Chi-
ralcel OD column. [d] Yields and ee values refer to those reported
in ref.[13a]
Figure 2. Proposed catalytic cycle for β-amino alcohols catalyzed
epoxidation.
(Table 6, Entry 1). More sterically hindered tertiary amino
alcohol 17 proved to be inactive under the same conditions
(Table 6, Entry 2). Although compound 18, the N,N-di-
methyl derivative of catalyst 8, furnished traces of the prod-
uct, it proved to be slightly more enantioselective than pri-
mary amino alcohol 8 (Table 6, Entry 3). (–)-N-methyl eph-
edrine (19) afforded a similar result in comparison to cata-
lyst 18 (Table 6, Entry 4). Finally, acyclic compound 20 gave
the product in slightly better yield but in racemic form
(Table 6, Entry 5).
TBHP first undergoes deprotonation by the β-amino
alcohol, which thus generates the active catalytic species,
that is, the ammonium A/tert-butyl peroxyanion ion pair.
The hydroxy group of the promoter then activates and ori-
entates trans-chalcone through hydrogen bonding with its
carbonyl group for the nucleophilic 1,4-addition of the tert-
butyl peroxy anion according to the accepted mechanism
for the Weitz–Scheffer epoxidation.[21] On the basis of the
proposed catalytic cycle, the basicity of the amine and hy-
drogen bonding interactions are fundamental in regulating
the activity of the promoters.
Solvation effects are of reduced importance in the stabili-
zation of charged and polar species when hexane is used as
the solvent. A more realistic idea on the basicity of second-
ary cyclic amines would be gained by considering the intrin-
sic basicity rather than the solution basicity. Intrinsic basic-
ity of cyclic amines has been estimated by experimental and
calculated gas-phase proton affinities.[22] Solvent leveling
effects on the pKBH+ measured in water (Table 7) for the
four-, five-, and six-membered cyclic amines would not be
expected in hexane. As a result, meaningful differences in
the basicities of the amines can be predicted by evaluation
of the proton affinities, and the four-membered ring amine
is the least basic. Detectable differences in calculated pKBH+
values were estimated in aprotic acetonitrile, which is a less
polar solvent than water (Table 7).[23]
Table 6. Epoxidation of 1a with tertiary β-amino alcohols and
TBHP.[a]
By taking this into account, the data reported in Tables 1
and 2 are more easily rationalized. Indeed, four-membered
catalyst 4a appeared significantly less active than catalysts
2b and 5a, whereas better performances are displayed by
compounds 2b and 5a, whose basic properties become
closer (Table 7).
[a] Molar ratios: 1/4a/TBHP, 1:0.30:1.4. [b] Isolated products after
flash chromatography. [c] Determined by HPLC analysis on Chi-
ralcel OD column.
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Asymmetric Epoxidation of trans-Chalcones
Table 7. Calculated and experimental gas-phase proton affinities of primary β-amino alcohols as catalysts in the epoxidation
+
and pKBH values for cyclic amines.
of trans-chalcone could be ascribed to the intramolecular
hydrogen bonding formed in the corresponding β-hydroxy
ammonium ions. Indeed, it has been proved, both experi-
mentally and by calculations, that gas-phase proton affin-
ities in structurally different primary β-amino alcohols are
related to the dihedral θ angle (CO–CN) with a maximum
value for θ = 0° and a minimum value for θ = 180°.[26] This
has been interpreted as the change in the internal hydrogen-
bonding interaction of the β-hydroxy ammonium ion.[27]
Therefore, to serve as active and enantioselective pro-
[a] Values given in kJ/mol as reported in ref.[22] [b] Values given in
moters basicity, electrostatic interactions, as well as intra-
kJ/mol as reported in ref.[22] [c] Values in water as reported in ref.[22]
and intermolecular hydrogen-bonding interactions, have to
be considered in the catalysis provided by β-amino alcohols.
To better understand the structure of the ammonium ions
+
[d] Calculated pKBH in acetonitrile.
In solution, direct interactions between functional involved in the ion pair, we then investigated the gas-phase
groups in a molecule are generally masked by the interfer- ammonium conformers of promoters 2b, 4a, 5a, 12a by
ing presence of functional groups of the solvent. Apart using B3LYP density functional theory (Gaussian 03W, 6-
from the gas phase, hexane can be considered an inert me- 31G* basis set).[28]
dium, where intra- and intermolecular hydrogen bonding
The lowest-energy conformers I and II of the most enan-
interactions of a functionalized molecule are exalted and tioselective catalysts 2b and 4a show the intramolecular hy-
play a decisive role in affecting physical properties and drogen bond between the oxygen atom of the OH group
eventually chemical activity. In the present study, we dis- with the N–H bond from the same side of the ring plane.
closed that simple primary β-amino alcohols catalyze the Conformers III and IV, where the hydrogen bonding is with
epoxidation of trans-chalcone and the enantioselectivity can the N–H bond on the opposite side of the ring plane,
be tuned to achieve an encouraging level.
proved to be 3.6 and 8.5 kJ/mol less stable than I and II,
The formation of the ion pair in hexane as the active respectively (Figure 3). The energetic differences observed
species (Figure 2) deserves some considerations: (i) On go- suggest that conformers I and II are likely involved in the
ing from tertiary to primary amino alcohols, ion-pairing ion pair during the epoxidation, which thus leads to a high
interactions increase as stronger localized charged ammo- level of enantioselectivity.
nium ions are formed that can better stabilize the unsol-
vated tert-butyl peroxyanion. (ii) Increasing alkyl substitu-
tion at the ammonium ion would preclude an optimized
electrostatic interaction with the anion and give rise to a
steric destabilization of the ion pair. This would explain the
higher activity generally assured by primary and secondary
cyclic amino alcohols with respect to acyclic secondary and
tertiary amino alcohols, which form a looser and more ste-
rically crowded ion pair. Moreover, the possibility of intra-
molecular hydrogen-bonding interactions between charged
N–H and the vicinal oxygen atom of the hydroxy group
would block the conformation of the β-hydroxy ammonium
ion and impart steric rigidity to the ion pair, which thus
influences the level of enantioselectivity. This would ac-
count for the remarkable difference observed in the enantio-
selectivities for the epoxidation of 1a by promoters 2c and
2d (Table 5, Entries 5 and 6).[24] Finally, the key role of the
hydroxy group in the catalyst is consistent with an intermo-
lecular hydrogen-bonding interaction with the oxygen atom
of the enone carbonyl group, which activates the enone
towards 1,4-addition of the peroxyanion while directing and
placing the partners in close proximity to react. Indeed, 2a
Figure 3. Calculated ammonium conformers of 2b (I–III) and 4a
(II–IV).
is the most active and enantioselective catalyst in compari-
son to 2c,d (Table 5, Entry 4).[25]
Again, catalysts 5a shows the most stable conformer V
Although primary amines are expected to be poorer pro- to have hydrogen bonding between the oxygen atom of the
moters on the basis of pKBH+ values, their activity can be OH group with the N–H bond on the same side of the ring
significantly modulated by structural modifications plane, but a smaller energy difference of 1.4 kJ/mol with the
(Tables 3 and 4). A contribution to the changeable activity less stable conformer VII is observed (Figure 4).
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A. Russo, A. Lattanzi
FULL PAPER
performed on Merck silica gel (60, particle size: 0.040–0.063 mm).
1H and 13C NMR spectra were recorded with Bruker DRX 400
and 300 spectrometers at room temperature in CDCl3 as solvent.
Chemical shifts for protons are reported by using residual CHCl3
as internal reference (δ = 7.26 ppm). Carbon spectra were refer-
enced to the shift of the 13C signal of CDCl3 (δ = 77.0 ppm). Op-
tical rotations were performed with a Jasco Dip-1000 digital polari-
meter by using the Na lamp. FTIR spectra were recorded as a thin
film on KBr plates by using Bruker Vector 22 spectrometer and
absorption maxima are reported in wavenumber (cm–1). MS (ESI)
was performed by using a Bio-Q triple quadrupole mass spectrome-
ter (Micromass, Manchester, UK) equipped with an electrospray
ion source. Melting points are uncorrected. All commercially avail-
able reagents were purchased from Aldrich. Petroleum ether (PE)
refers to light petroleum ether. trans-Chalcones that were not com-
mercially available were prepared by aldol condensation by using
standard conditions. Hexane of HPLC grade, stored under preacti-
vated molecular sieves (4 Å), was used as solvent for the epoxid-
ation. Compound 5a was prepared according to the literature.[29]
Compounds 13, 14, and 18 were synthesized and characterized by
comparison of NMR spectra with previously reported data.[30] Ab-
solute configuration of the predominant enantiomer of epoxides
was determined by comparison with the HPLC retention times by
using Daicel Chiralcel OD and Daicel Chiralpak AD columns, as
reported in the literature.[13,31]
Figure 4. Calculated ammonium conformers of 5a (V–VII) and 12a
(VI–VIII).
Finally, conformers VI and VIII of the flexible acyclic
catalyst 12a are almost comparable, as they have an energy
difference of 0.6 kJ/mol. In the case of catalysts 5a and 12a,
all ammonium conformers V–VIII are reasonably active in
the epoxidation, which thus affords an average result in
terms of asymmetric induction.
General Procedure for the Epoxidation of trans-Chalcone: TBHP
(5–6  decane solution, 37 µL, 0.21 mmol) was added to a stirred
solution of the β-amino alcohol (0.045 mmol) and trans-chalcone
(31.2 mg, 0.150 mmol) in hexane (0.300 mL) at room temperature.
Strirring was maintained for the indicated time (monitoring by
TLC) in the Tables. The crude reaction mixture was directly puri-
fied by flash chromatography on silica gel (PE/diethyl ether, 99:1)
to provide the epoxy ketone.
Conclusions
Supporting Information (see footnote on the first page of this arti-
cle): Experimental procedures and characterization of products 4a,
5a, 12a–d; computational data of conformers I–VIII.
We studied the catalytic performance of easily accessible
primary, secondary, and tertiary β-amino alcohols in the
asymmetric epoxidation of trans-chalcones. They are able
to catalyze the transformation with variable efficiency. In
terms of activity and enantioselectivity, we confirmed that
secondary pyrrolidine-based compounds are the best pro-
moters in comparison to four- and six-membered ring ana-
logues. Moreover, we disclosed that primary β-amino
alcohols, straightforwardly available in one step from -
amino acid esters, are able to catalyze the epoxidation. Sub-
tle modifications to the substitution pattern of the skeleton
of primary β-amino alcohols were found to deeply influence
the outcome of the reaction and encouraging levels of
asymmetric induction were achieved. The influence of tun-
able properties such as hydrogen-bonding interactions and
steric and electronic effects has been recognized; hence,
these factors will have to be carefully taken into account
for future catalyst development.
Acknowledgments
Ministero Italiano dell’Università e Ricerca Scientifica (MIUR) is
gratefully acknowledged for financial support. We thank Prof. Ric-
cardo Zanasi and Dr. Amedeo Capobianco for helpful suggestions
in DFT calculations, Maria Lamberti for experimental support,
and Dr. Patrizia Iannece for MS analyses.
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Experimental Section
General Details: All reactions requiring dry or inert conditions were
conducted in flame-dried glassware under a positive pressure of
argon. THF was freshly distilled before use from LiAlH4. Reactions
were monitored by thin-layer chromatography (TLC) on Merck sil-
ica gel plates (0.25 mm) and visualized by UV light or by phos-
phomolybdic acid/ethanol spray test. Flash chromatography was
[5] a) F. A. Davies, M. E. Haracal, S. B. Awad, J. Am. Chem. Soc.
1983, 105, 3123; b) F. A. Davies, R. Thimma Reddy, M. C.
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Asymmetric Epoxidation of trans-Chalcones
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Received: February 5, 2008
Published Online: April 15, 2008
Eur. J. Org. Chem. 2008, 2767–2773
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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