Epoxidation of (E,E)-cinnamylideneacetophenones with hydrogen peroxide and iodosylbenzene with salen-MnIII as the catalyst

Article abstract of DOI:10.1002/ejoc.200700123

(E,E)-Cinnamylideneacetophenones 3a-j were epoxidized under mild conditions with Jacobsen's catalyst 4 and hydrogen peroxide or iodosylbenzene as oxidants. γ,δ-Monoepoxides and a diastereomeric mixture of α,β:γ,δ-diepoxides were obtained in each case, and

Full text of DOI:10.1002/ejoc.200700123

FULL PAPER
DOI: 10.1002/ejoc.200700123
Epoxidation of (E,E)-Cinnamylideneacetophenones with Hydrogen Peroxide
and Iodosylbenzene with Salen-MnIII as the Catalyst
Clementina M. M. Santos,[a,b] Artur M. S. Silva,*[b] José A. S. Cavaleiro,[b] Albert Lévai,[c]
and Tamás Patonay[c]
Dedicated to Prof. Miguel Yus on the occasion of his 60th birthday
Keywords: Cinnamylideneacetophenones / Epoxidation / Jacobsen’s catalyst / Hydrogen peroxide / Iodosylbenzene
(E,E)-Cinnamylideneacetophenones 3a–j were epoxidized
under mild conditions with Jacobsen’s catalyst 4 and hydro- sponding γ,δ-monoepoxides as well as (E)-2,3-trans-3-hy-
gen peroxide or iodosylbenzene as oxidants. γ,δ-Monoepox- droxy-2-styryl-4-chromanones, which originated from the in
ides and a diastereomeric mixture of α,β:γ,δ-diepoxides were situ cyclisation of 2,3-epoxy-1-(2-hydroxyphenyl)-5-phenyl-
eneacetophenones 3h,j led to the formation of the corre-
obtained in each case, and only the α,β-monoepoxide of 4-
nitrocinnamylideneacetophenone (3d) was isolated. The
presence of a methyl group in the vinylic moiety of substrates
3i,j allowed the formation of two γ,δ-monoepoxide dia-
4-penten-1-ones. The structures of all new compounds and
the stereochemistry of the mono- and diepoxide dia-
stereomers were established by NMR studies.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
stereomers. The epoxidation of (E,E)-2Ј-hydroxycinnamylid- Germany, 2007)
(E,E)-Cinnamylideneacetophenones constitute an impor-
Introduction
tant group of unsaturated ketones that are prepared from
the aldol condensations of appropriate acetophenones and
cinnamaldehydes. Over the last few decades, considerable
attention has been payed to the synthesis of these com-
pounds, and many chemical transformations were ac-
complished with a great number of derivatives.[32–34]
Salen MnIII complexes are efficient catalysts for the epox-
idation of various olefinic compounds.[1–3] Since the pion-
eering work of Kochi et al.,[4] many contributors have re-
viewed a wide range of applications of these powerful and
selective catalysts.[5–7] Several oxidants have been used as
effective oxygen donors in these epoxidations, with iodo-
sylbenzene[8–11] and sodium hypochlorite[12–14] being the
most frequently reported. Among other common olefin oxi-
dants hydrogen peroxide,[15–17] oxone®,[18] dimethyldioxir-
ane (DMD),[19–23] m-chloroperbenzoic acid (MCPBA),[24]
molecular oxygen[25] and more recently also tetrabutylam-
monium monosulfate[24,26,27] and tetrabutylammonium per-
iodate[28] have been used. Alkene epoxidation can also be
achieved with simple co-catalysts such as imidazoles, pyri-
dines and tertiary amine N-oxides, which act as axial li-
gands and, in some cases, as phase-transfer catalysts.[29–31]
Studies on the asymmetric epoxidation reaction devel-
oped by Juliá and Colonna[35] showed that a wide variety
of substrates, such as enones, enediones and unsaturated
keto esters, could be oxidized into optically active epoxides
with basic hydrogen peroxide and poly(amino acids).[36–38]
Later on, the same group[39,40] reported the use of a non-
aqueous variant of the Juliá–Colonna reaction for the epox-
idation of dienones and trienones, which includes the syn-
thesis of α,β-monoepoxides of ketones related to cinnamyli-
deneacetophenones. In 2001, our group reported the oxi-
dation of cinnamylideneacetophenones with dimethyldioxi-
rane,[41] which also led to the formation of α,β-monoepox-
ides as well as diastereomeric mixtures of α,β:γ,δ-diepox-
ides. Since then, as far as we know, no epoxidation studies
have been reported for these kinds of unsaturated deriva-
tives as substrates. On this basis, we launched a new study
of the epoxidation of (E,E)-cinnamylideneacetophenones
3a–j, catalysed by the commercially available Jacobsen’s cat-
alyst 4 [salen MnIII, N,NЈ-bis(3,5-di-tert-butylsalicylidene)-
1,2-cyclohexanediaminomanganese(III) chloride] and with
hydrogen peroxide and iodosylbenzene as oxidants. These
[a] Department of Agro-Industries, Escola Superior Agrária de
Bragança,
5301-855 Bragança, Portugal
Fax: +351-273-325405
E-mail: clems@ipb.pt
[b] Department of Chemistry, University of Aveiro,
3810-193 Aveiro, Portugal
Fax: +351-234-370084
E-mail: arturs@dq.ua.pt
[c] Department of Organic Chemistry, University of Debrecen,
4010 Debrecen, Hungary
Fax: +36-52-453836
E-mail: alevai@puma.unideb.hu
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A. M. S. Silva et al.
FULL PAPER
investigations were the continuation of our previous work tained. When performing the same reaction at higher tem-
on the epoxidation of 2-styrylchromones, a related but cy-
perature (40 °C), TLC showed not only the starting mate-
rial 3a and the γ,δ-monoepoxide 5a but also a new com-
pound with an even lower Rf value. The 1H NMR spectrum
of the isolated new product identified it as a diastereomeric
mixture (nearly 1:1) of 2,3:4,5-diepoxy-1,5-diphenylpentan-
1-ones (α,β:γ,δ-diepoxides, 6a),[45] the stereochemistry of
the diastereomers being established by NOE (Scheme 2, see
NMR spectroscopy discussion).
clic dienone system.[42]
Results and Discussion
Syntheses
(E,E)-Cinnamylideneacetophenones 3a–c,e,f,h–j were
prepared by aqueous base-catalysed aldol reaction of cinnam-
aldehydes and acetophenones in methanolic solutions, ex-
cept for the nitro derivatives, which were prepared under
milder conditions (NaH/THF) to afford the (E,E)-nitrocin-
namylideneacetophenones 3d,g in better yields (Scheme 1).
Since cinnamaldehydes 2b–d are not commercially available,
we have synthesized them by the method developed by Ca-
chi and co-workers,[43] involving a two-step approach,
namely a Heck reaction followed by hydrolysis.
Several attempts were made to improve the yield of the
epoxidation of (E,E)-cinnamylideneacetophenone (3a) by
varying the amount of oxidant, temperature and reaction
time and adding various nitrogen co-catalysts. The best re-
sults were achieved with hydrogen peroxide as the oxidant
(3 equiv.), salen MnIII complex 4 as the catalyst (0.05 equiv.)
and 1-methylimidazole (1-MeIm) as the co-catalyst at 40 °C
for 4 h. These conditions gave a 21% yield of γ,δ-monoe-
poxide 5a, a 10% yield of α,β:γ,δ-diepoxide 6a and 38% of
starting material 3a was recovered (Table 1, Entry 1).
These optimized conditions were applied to the epoxid-
ation of cinnamylideneacetophenones 3b–j, and the results
are presented in Table 1. The epoxidation of cinnamylidene-
acetophenones 3c–g afforded similar results, yielding γ,δ-
monoepoxides 5c–f, α,β:γ,δ-diepoxides 6c–g and some reco-
vered starting material (Table 1). However, in the case of 4-
nitrocinnamylideneacetophenone (3d) it was also possible
to isolate the α,β-monoepoxide 7d (Table 1, Entry 4). This
can be explained by the electron-withdrawing effect of the
nitro group, which overrules the effect of the carbonyl
group, making the Cα=Cβ bond more nucleophilic. TLC
analysis of the epoxidation reaction of 4-methoxycinnamyl-
ideneacetophenone (3b) showed the formation of several
products, and all attempts to isolate them failed (Table 1,
Entry 2). It is very likely that a facile ring opening of the
desired epoxide 5b, due to the stabilization of the benzylic
The first attempt to epoxidise (E,E)-cinnamylideneaceto-
phenone (3a) with hydrogen peroxide in a 1:1 mixture of
dichloromethane/methanol without catalyst according to
the method reported by Lévai et al.[44] failed to give any
epoxide, and only the unreacted starting material was recov-
ered. A similar reaction with 0.05 equiv. of Jacobsen’s cat-
alyst 4 for 4 h at room temperature revealed a new product
(11%) with a lower Rf value in addition to the starting ma-
1
terial 1a. The analysis of the H, 13C, HSQC and HMBC
NMR spectra of this new compound confirmed the forma-
tion of the 4,5-epoxy-1,5-diphenyl-2-penten-1-one (γ,δ-ep-
oxide, 5a)[45]. The formation of this compound can be ex-
plained in terms of the less electrophilic character of the
Cγ=Cδ bond compared with that of the Cα=Cβ bond, since
the epoxidation of alkenes catalysed by salen MnIII com-
plexes has been demonstrated to take place preferentially
on double bonds with higher electron density.[46,47] It is
noteworthy that in the epoxidation of these types of com- cation, and subsequent secondary reactions are responsible
pounds with DMD[41] α,β-monoepoxides have been ob- for this failure.
Scheme 1.
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Epoxidation of Cinnamylideneacetophenones
FULL PAPER
Scheme 2.
Table 1. Yields in the epoxidation reactions of (E,E)-cinnamylid- with the smallest Rf value was assigned as (E)-2,3-trans-3-
eneacetophenones 3a–j.
hydroxy-2-styryl-4-chromanone (8h), the product of the in
[a]
Entry Reactant
Product
H2O2
PhIO[b]
% Yield
situ cyclisation of α,β-epoxide 7h (Scheme 3 and Table 1,
Entry 8). This cyclisation product 8h is different from the
one obtained in the epoxidation of 3h with DMD,[41] where
the cyclisation of a α,β:γ,δ-diepoxide gave a coumaranone
derivative. In the present study, the cyclisation of the α,β-mono-
epoxide 7h gave chromanone 8h, as was reported for 2Ј-
hydroxychalcone epoxides.[48–50] The observed preference of
the attack of the phenolic hydroxy group at Cβ can be ra-
tionalized in terms of the high stability of the allylic Cβ
carbocation and its better solvation by methanol in com-
parison with solvation by the acetone used in the DMD
experiments.
In the epoxidation of γ-methylcinnamylideneaceto-
phenone (3i) with hydrogen peroxide, two isomeric γ,δ-
monoepoxides have been isolated and characterized by
NMR spectroscopy, and no α,β:γ,δ-diepoxide was detected
(Scheme 3 and Table 1, Entry 9). This surprising regioselec-
tivity can be explained in terms of the enhanced nucleophi-
licity of the Cγ=Cδ bond due to the electron-donating effect
of the methyl group, making the double bond more sensi-
tive for the attack of the electrophilic oxidizing species. The
NOESY spectra of these two diastereomers allowed us to
assign their stereochemistry and to identify them as trans-
9i and cis-9i (see the NMR discussion below). The forma-
tion of these two diastereomers can be envisaged by the
mechanistic proposal for the epoxidation reactions of al-
kenes with the salen MnIII catalyst, where the alkenes can
react in a stepwise radical process followed by ring closure
from both sides of the molecule, affording the two possible
diastereomers.[51,52] This means that the incorporation of
the methyl group initiates a shift in the mechanism, since
no diastereomeric γ,δ-monoepoxides 5a,c–g were observed
% Yield % Effective yield[c]
1
2
3
4
3a
3b
3c
3d
5a
6a
5b
21
10
34
17
18
43
see text
6b
5c
13
9
9
18
7
15
9
11
23
22
33
39
18
41
15
55
6c[d]
5d
17
38
15
40
18
19
10
6d[d]
7d
5
3e
3f
3g
3h
3i
5e
25
11
14
7
6e[d]
5f
6
6f[d]
5g
[e]
[e]
[e]
7
–
–
–
6g[d]
5h
10
11
14
16
26
19
13
10
23
14
19
26
43
29
19
15
62
4
2
60
7
13
9
8
8h
9
trans-9i
cis-9i
8j
10
3j
trans-9j
cis-9j
3
[a] H2O2 (3 equiv.), catalyst 4 (0.05 equiv.), 1-MeIm (0.7 equiv.),
40 °C, 4 h, 1:1 MeOH/CH2Cl2. [b] PhIO (2 equiv.), catalyst 4
(0.05 equiv.), PyNO (0.5 equiv.), room temp., 4 h, MeCN. [c] Yield
calculated on the basis of the amount of the reacted cinnamylidene-
acetophenone. [d] Obtained as a diastereomeric mixture (for ratios,
see the Experimental Section). [e] None detected.
TLC analysis of the epoxidation of 2Ј-hydroxy-cinnamyl-
ideneacetophenone (3h) with hydrogen peroxide revealed
the presence of three spots; the one with the largest Rf value
proved to be unreacted starting material 3h, the one with
the next-largest Rf value was identified as 4,5-epoxy-1-(2-
hydroxyphenyl)-5-phenyl-2-penten-1-one (5h) and the one in the reaction of substrates lacking this unit.
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A. M. S. Silva et al.
FULL PAPER
Scheme 3.
Finally, the epoxidation of 2Ј-hydroxy-γ-methylcinnamyl- phenones 3b–j, and the corresponding epoxidation products
ideneacetophenone (3j) afforded the expected products. In were obtained with the yields presented in Table 1
accordance with the reactivity patterns outlined above and (Scheme 2).
due to the presence of the methyl group at Cγ, both γ,δ-
Table 2. Isolated yields in the epoxidation reactions of (E,E)-cinnam-
monoepoxides trans-9j and cis-9j have been obtained. The
ylideneacetophenone (3a) with pyridine N-oxide (PyNO) and 4-
formation of 4-chromanone 8j due to the presence of the
2Ј-hydroxy group (Scheme 3 and Table 1, Entry 10) re-
sembles the formation of 8h.
phenylpyridine N-oxide (PPNO) as co-catalysts and iodosylben-
zene as the oxidant.
Entry
Co-catalyst
t [h]
% Yield
Since the combination of iodosylbenzene and Jacobsen’s
catalyst constitutes an efficient oxidizing system in the case
of (E)-2-styrylchromones,[42] we examined the epoxidation
of (E,E)-cinnamylideneacetophenones 3a–j under the same
conditions. Several reactions were performed to optimize
the conditions. First, an acetonitrile solution of 3a was
treated with 2 equiv. of iodosylbenzene and a catalytic
amount of salen MnIII. After 24 h at room temperature,
preparative TLC analysis revealed the presence of 3 prod-
ucts. The first spot, corresponding to starting material 3a,
in marginal quantity, a second spot with a smaller Rf value,
corresponding to γ,δ-monoepoxide 5a (5%) and the third
spot, corresponding to α,β:γ,δ-diepoxide 6a (4%)
(Scheme 2). This result led us to use co-catalysts, which
5a
6a
1
2
3
4
5
6
7
8
PyNO
PPNO
PyNO
PPNO
PyNO
PPNO
PyNO
PPNO
PyNO
PPNO
PyNO
PPNO
4
18
13
19
15
17
19
13
21
–
43
21
43
35
35
31
32
36
–
12
24
48
72
96
9
10
11
12
17
–
14
41
–
31
The epoxidation of alkenes catalysed by salen MnIII com-
were found to be beneficial in the reaction with hydrogen plexes is usually favoured by the presence of electron-donat-
peroxide, as well. The yields from the epoxidation of cinnam- ing substituents, and the corresponding epoxides are ob-
ylideneacetophenone (3a) were tripled with pyridine N- tained in better yields.[46,47] Our results presented in Table 1
oxide (PyNO) and 4-phenylpyridine N-oxide (PPNO). A (Entries 1–4) seem to indicate the contrary. However, these
study of the influence of reaction time on the epoxidation results cannot be explained by the reactivity of the unsatu-
of 3a with these two co-catalysts was then carried out rated ketones 3a–d, but by the stability of the obtained ep-
(Table 2). With PyNO, only 4 h were necessary to achieve oxides 5a–d and 6a–d. In the presence of electron-with-
the best epoxidation yields (i.e. 18% of γ,δ-monoepoxide drawing substituents, the epoxides 5d, 6d and 7d were ob-
5a and 43% of α,β:γ,δ-diepoxide 6a). After 12 h, the yields tained in good combined yields (34% with H2O2 and 94%
decreased, particularly in the case of 6a. With PPNO, a with PhIO, Table 1, Entry 4), whereas in the case of elec-
gradual increase in the formation of 5a and 6a within the tron-donating substituents, the yields decreased (combined
reaction time was observed, and 72 h was needed to achieve yields of 5c + 6c were 22% with H2O2 and 34% with PhIO,
similar yields to those obtained with PyNO. After 72 h, a in comparison with 31% and 61%, respectively, found in
decrease in the yields of γ,δ-monoepoxide 5a and α,β:γ,δ- the reactions of the parent compound 3a). In the presence
diepoxide 6a was observed. The optimized conditions of a strong electron-donating group we could not isolate
(2 equiv. of iodosylbenzene, 0.05 equiv. of catalyst 4, any epoxide (Table 1, Entry 2). This conclusion was con-
0.5 equiv. of PyNO, acetonitrile, 4 h at room temperature) firmed when the epoxidation of 3b was carried out in deu-
were applied to the other (E,E)-cinnamylideneaceto- terated acetonitrile and monitored by 1H NMR spec-
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Epoxidation of Cinnamylideneacetophenones
FULL PAPER
troscopy. After several minutes of reaction under the condi- in the aliphatic region (δ = 3.59–3.61 ppm and δ = 3.86–
tions presented in Table 1, we observed the signals of γ,δ- 4.01 ppm), which were attributed to the resonances of δ-H
monoepoxide 5b (doublet of doublets at δ = 6.54 ppm, J = and γ-H, respectively. Another main feature of these spectra
15.4 and 7.4 Hz, corresponding to the resonance of β-H) was the doublet of doublets at δ = 6.92–6.95 ppm, corre-
and other small signals in the aliphatic region (δ = 4.12– sponding to the resonance of β-H, which appears at lower
5.01 ppm), which increased with the reaction time, probably frequency values than that of α-H (δ = 7.28–7.33 ppm). The
due to the decomposition of monoepoxide 5b. The charac- 3JαH–βH value of about 15 Hz indicates a trans configura-
teristic signal of monoepoxide 5b did not increase, and no tion of the Cα=Cβ bond of γ,δ-monoepoxides 5a,c–f, as ex-
signals typical of α,β:γ,δ-diepoxide 6b were observed.
pected on the basis of the trans,trans configuration of the
The presence of electron-donating or electron-with- starting (E,E)-cinnamylideneacetophenones 3a,c–f. The
drawing substituents on the A ring of cinnamylideneaceto- structure of monoepoxides 5a,c–f was supported by the
phenones did not affect the yields of the obtained epoxides connectivities found in their HMBC spectra, mainly those
(Table 1, Entries 1 and 5–7), while the presence of a weak of α-H and β-H with the carbonyl C atom (δ = 187.7–
electron-donating substituent on the vinylic moiety slightly 189.5 ppm) and also of the δ-H with C-1 (δ = 133.0–
increased the yield of the epoxidation reaction (Table 1, En- 143.4 ppm) and C-2,6 (δ = 125.5–126.3 ppm) (Figure 1), al-
tries 1 and 9). However, the cis-γ,δ-monoepoxide cis-9i was lowing us to confirm the presence of the epoxy ring in the
obtained in a better yield than the trans-γ,δ-monoepoxide γ,δ-position and the assignments of α-H, β-H, γ-H and δ-
trans-9i with hydrogen peroxide, while the use of iodosyl- H.
benzene resulted in the trans-γ,δ-monoepoxide trans-9i as
the major product with a high trans/cis (8.6:1, Table 1, En-
try 9). This difference can be rationalized in terms of shift-
ing the mechanism of the epoxidation from the stepwise
radical process (vide supra) towards a concerted one in the
less solvating acetonitrile; this solvent can stabilize the radi-
caloid species to a lesser extent. The presence of a 2Ј-hy-
droxy group drastically decreased the total yield of the ob-
tained epoxides, especially with iodosylbenzene as the oxi-
dant (Table 1, Entries 1, 8 and 10).
After the analysis of all the results collected in Table 1
we can conclude that the epoxidation of cinnamylideneace-
tophenones 3a,c–f,i with iodosylbenzene gives the epoxides
5a,c–f,i + 6a,c–f,i in better total yields than did the reaction
with hydrogen peroxide, and this might be due to the insta-
bility of the obtained epoxides, as described above. From
Table 1 one can also notice that the yields of γ,δ-monoepox-
ides 5a,c–f are double those of the α,β:γ,δ-diepoxides 6a,c–
f when the epoxidation was performed with hydrogen per-
oxide as the oxidant, but when iodosylbenzene was the oxi-
dant we observed the inverse, (i.e., the α,β:γ,δ-diepoxides
6a,c–h were obtained in better yields than were the γ,δ-
monoepoxides 5a,c–h.) This difference can be interpreted in
terms of the higher sensitivity of the α,β:γ,δ-diepoxides to-
ward attack of the nucleophilic solvent, decreasing the iso-
lated yields of the diepoxides in the hydrogen peroxide sys-
Figure 1. Important connectivities found in the HMBC spectra of
compounds 5a,c–f,h, 6a,c–g, 7d and 9i.
tems.
The unequivocal assignment of 2,3-epoxy-1-phenyl-5-(4-
Since we used Jacobsen’s catalyst 4 in the described epox- nitrophenyl)-4-penten-1-one (7d) was also based on the
idations, and therefore, the reactions were effected by a chi- connectivities found in its HMBC spectrum. The signal ap-
ral non-racemic MnVoxo species in both methods, it was pearing as a doublet in the aliphatic region (δ = 4.36 ppm)
important to determine the enantiomeric ratio of the ob- correlates with the carbonyl C atom (δ = 193.0 ppm), and
tained monoepoxides. Unfortunately, HPLC analysis mea- thus, was assigned to the resonance of α-H. The corre-
surements of γ,δ-monoepoxide 5a with a chiral column lations of the vinylic protons γ-H and δ-H with C-1 (δ =
(Chiralcel OD) showed that no stereodifferentiation took 141.7 ppm) and C-2,6 (δ = 127.2 ppm), respectively, con-
place, and the product was a racemic mixture of the two firm the structure of α,β-monoepoxide 7d (Figure 1).
enantiomers.
The main feature of the 13C NMR spectra of the γ,δ-
monoepoxides 5a,c–f was the resonance of the carbonyl
carbon, which appeared at high frequency values (δ =
Nuclear Magnetic Resonance Spectroscopy
The 1H NMR spectra of the 1,5-diaryl-4,5-epoxy-2- 187.7–189.5 ppm). The unequivocal assignments of the
penten-1-ones 5a,c–f revealed the presence of two signals other C resonances were made with the aid of HSQC and
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A. M. S. Silva et al.
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HMBC spectra. At lower frequency values it was possible mixture as 51–58% of isomer A and 42–49% of isomer B
to identify the C resonances of C-γ and C-δ at δ = 60.2– was calculated from the integrated area of the correspond-
61.3 ppm and 61.4–61.6 ppm, respectively. The C reso- ing proton signals. This stereochemistry was based on the
nances of C-α and C-β appeared at δ = 127.0–128.0 ppm proximities between α-H and γ-H and between β-H and δ-
and 142.1–143.7 ppm, respectively, and the latter was as- H for diastereomers A and between α-H and δ-H and be-
signed to the higher frequency values on the basis of the tween β-H and γ-H for diastereomers B (Figure 2). In the
mesomeric deshielding effect of the carbonyl group.
HMBC spectra of α,β:γ,δ-diepoxides 6a,c–g, the corre-
1
The H NMR spectra of the γ-methyl-γ,δ-monoepoxides lations between the carbonyl C atom resonances (δ = 191.2–
trans-9i,j and cis-9i,j showed two singlets at δ = 1.31– 193.3 ppm) and the signals appearing as a doublet at δ =
1.74 ppm and 4.05–4.24 ppm, assigned to the proton reso- 3.90–4.08 ppm allowed us to assign these proton resonances
nances of the γ-methyl group and δ-H, respectively. The to α-H (since there are no correlation between C=O and δ-
presence of the γ-methyl group also promoted important H). From the 2D-COSY experiments, all the proton reso-
changes in the resonances of α-H and β-H, with the reso- nances of the α,β:γ,δ-diepoxide system have been assigned:
nance of β-H being the most affected, in contrast to that γ-H (doublet of doublets at δ = 3.18–3.22 ppm), β-H (doub-
of the γ,δ-monoepoxides, which are unsubstituted at the γ- let of doublets at δ = 3.34–3.54 ppm), δ-H (doublet at δ =
position (5a,c–f). Thus, the resonances assigned to α-H (δ 3.90–4.08 ppm) and α-H (doublet at δ = 4.29–4.36 ppm).
= 6.96–7.34 ppm) appeared at higher frequency than those The aromatic region of the 1H NMR spectra of α,β:γ,δ-
assigned to β-H (δ = 6.59–7.19 ppm). The configuration of diepoxides 6a,c–g presents several multiplets, which were
the two diastereomers trans-9i,j and cis-9i,j were established assigned with the aid of 2D NMR spectra and by compari-
by the NOE signals found in their NOESY spectra. For the sons with similar compounds.[41]
cis-9i,j diastereomers, a strong NOE cross peak between the
The 13C NMR spectra of the diastereomeric mixture of
signals of the γ-methyl protons and that of δ-H was ob- α,β:γ,δ-diepoxides 6a,c–g presents a duplication of signals
served; whereas for the trans-9i,j diastereomers, a strong in three distinct zones: those at lower frequency values (δ =
NOE cross peak between the signals of the γ-methyl pro- 53.9–59.8 ppm), assigned to the C resonances of the
tons and that of 2,6-H of the phenyl ring was found (see α,β:γ,δ-diepoxy moiety, those at intermediate frequency val-
Figure 2).
ues (δ = 114.0–164.3 ppm), assigned to the C resonances of
The 1H NMR spectra of 2Ј-hydroxy-cinnamylideneaceto- the aromatic rings and those at higher frequency values (δ
phenone γ,δ-monoepoxides 5j, trans-9j and cis-9j showed a = 191.2–193.1 ppm and 191.4–193.3 ppm), attributed to the
singlet corresponding to the resonance of the hydroxy pro- resonance of the carbonyl C atom of diastereomers A and
ton (2Ј-OH) at δ = 12.38–12.60 ppm. This signal appears at B, respectively. The resonances of the carbonyl carbons of
high frequency values due to an intramolecular hydrogen diastereomers A showed higher frequency values than those
bond with the carbonyl group.
of the diastereomers B, except for the nitro derivatives 6d,g,
1
The H NMR spectra of α,β:γ,δ-diepoxides 6a,c–g are where the resonances of the carbonyl C atoms appeared in
quite complex, presenting two distinct regions (aliphatic reverse order. The C resonances of C-α, C-β, C-γ and C-δ
and aromatic). In the aliphatic region, the presence of two of diastereomers A and B were assigned with the aid of
groups of four signals indicates a diastereomeric mixture of the HSQC spectra, appearing at δ = 54.4–54.7 ppm, 57.2–
these diepoxides. The stereochemistry of both dia- 57.8 ppm, 59.4–59.8 ppm, 56.1–57.3 ppm and δ = 53.9–
stereomers A and B was established by the NOE signals 54.6 ppm, 55.8–56.6 ppm, 58.3–59.1 ppm and 55.3–
found in their NOESY spectra, and the composition of the 56.4 ppm, respectively.
Figure 2. Main NOE cross peaks found in the NOESY spectra of α,β:γ,δ-diepoxides 6a,c–g and γ-methyl-γ,δ-monoepoxides 9i,j.
2882
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Eur. J. Org. Chem. 2007, 2877–2887

Epoxidation of Cinnamylideneacetophenones
FULL PAPER
(300 MHz, CDCl3): δ = 2.37 (s, 3 H, 4-CH3), 6.95–7.06 (m, 2 H,
γ-H and δ-H), 7.07 (d, J = 14.8 Hz, 1 H, α-H), 7.18 (d, J = 8.1 Hz,
2 H, 3,5-H), 7.40 (d, J = 8.1 Hz, 2 H, 2,6-H), 7.49 (dd, J = 8.0 and
7.3 Hz, 2 H, 3Ј,5Ј-H), 7.57 (tt, J = 7.3 and 1.8 Hz, 1 H, 4Ј-H), 7.56–
7.68 (m, 1 H, β-H), 7.98 (dd, J = 8.0 and 1.8 Hz, 2 H, 2Ј,6Ј-H)
ppm. 13C NMR (75 MHz, CDCl3): δ = 21.4 (4-CH3), 124.9 (C-α),
126.0 (C-γ), 127.3 (C-2,6), 128.4 (C-2Ј,6Ј), 128.5 (C-3Ј,5Ј), 129.6
(C-3,5), 132.6 (C-4Ј), 133.4 (C-1), 138.3 (C-1Ј), 139.5 (C-4), 142.1
(C-δ), 145.2 (C-β), 190.6 (C=O) ppm. MS: m/z (%) = 248 (100)
[M]+, 247 (33), 233 (28), 205 (15), 171 (8), 157 (15), 143 (24), 141
(13), 128 (36), 115 (14), 105 (29), 91 (8), 77 (27), 51 (7). C18H16O
(248.32): calcd. C 87.06, H 6.49; found C 86.78, H 6.53.
The assignment of the C resonances of all compounds
was confirmed by the connectivities found in the HMBC
spectra (Figure 1).
Experimental Section
General Remarks: Melting points were measured with a Reichert
Thermovar apparatus fitted with a microscope and are uncor-
rected. NMR spectra were recorded with a Bruker Avance 300
spectrometer (300.13 MHz for 1H and 75.47 MHz for 13C) in
CDCl3. Chemical shifts (δ) are reported in ppm and coupling con-
stants (J) in Hz with TMS as an internal standard. Unequivocal
13C assignments were made with 2D gHSQC and gHMBC (delays
for one-bond and long-range C/H couplings were optimised for 145
and 7 Hz, respectively) experiments. Electron impact (EI, 70 eV)
MS were recorded with VG Autospec Q and M spectrometers. Ele-
mental analyses were obtained with a LECO 932 CHNS analyser.
Synthesis of (E,E)-Nitrocinnamylideneacetophenones 3d,g: Sodium
hydride (1.36 g, 56.5 mmol) was added to a solution of the appro-
priate acetophenone (25.7 mmol) in dry THF (80 mL), and the
mixture was cooled to room temperature. The appropriate cinnam-
aldehyde (30.8 mmol) in dry THF (100 mL) was added, and the
reaction mixture was stirred for 12 and then poured into a mixture
of water (100 mL) and ice (100 g) and acidified with hydrochloric
acid to pH ≈ 2. The solid obtained was filtered, taken up in dichlo-
romethane and washed with water. The organic layer was dried
and concentrated, and the residue was purified by silica gel column
chromatography with a 1:1 mixture of light petroleum/dichloro-
methane as the eluent. The solvent was evaporated, and the residue
was recrystallised from ethanol, giving the cinnamylideneaceto-
phenones 3d,g as yellow crystals.
Preparative TLC was performed with Merck silica gel 60 DGF254
.
Column chromatography was performed with Merck silica gel 60
(70–230 mesh). HPLC was performed with a Chiralcel OD column
with hexane/2-propanol (90:10, v/v) as the eluent and a flow rate
of 0.7 mL/min. Under these conditions, the enantiomers of epoxide
5a were detected at 20 min and 21 min, respectively. All chemicals
and solvents used were obtained from commercial sources and used
as received or dried with standard procedures. Cinnamaldehydes
2b–d have been prepared by a literature method.[43] Iodosylbenzene
was prepared by hydrolysis of the commercially available iodo-
benzene diacetate under basic conditions.[4]
(E,E)-4-Nitrocinnamylideneacetophenone (3d): Yield of 3.44 g
(48%). M.p. 171–173 °C (recrystallised from ethanol). 1H NMR
(300 MHz, CDCl3): δ = 7.05 (d, J = 15.5 Hz, 1 H, δ-H), 7.07–7.21
(m, 1 H, γ-H), 7.22 (d, J = 14.9 Hz, 1 H, α-H), 7.51 (t, J = 7.8 Hz,
2 H, 3Ј,5Ј-H), 7.60 (dd, J = 14.9 and 10.7 Hz, 1 H, β-H), 7.61 (t,
J = 7.3 Hz, 1 H, 4Ј-H), 7.64 (d, J = 8.8 Hz, 2 H, 2,6-H), 7.99 (dd,
J = 7.8 and 1.6 Hz, 2 H, 2Ј,6Ј-H), 8.24 (d, J = 8.8 Hz, 2 H, 3,5-H)
ppm. 13C NMR (75 MHz, CDCl3): δ = 124.2 (C-3,5), 127.7 (C-
2,6), 127.8 (C-α), 128.4 (C-2Ј,6Ј), 128.7 (C-3Ј,5Ј), 131.0 (C-γ), 133.0
(C-4Ј), 137.8 (C-1Ј), 138.5 (C-δ), 142.3 (C-1), 143.1 (C-β), 147.6 (C-
4), 190.1 (C=O) ppm. MS: m/z (%) = 279 (100) [M]+, 278 (21), 232
(17), 204 (17), 202 (16), 157 (36), 128 (39), 127 (21), 115 (21), 105
(48), 102 (13), 91 (6), 89 (7), 83 (8), 77 (63), 63 (7), 51 (22).
C17H13NO3 (279.29): calcd. C 73.11, H 4.69, N 5.02; found C
72.93, H 5.03, N 5.18.
General Procedure for the Synthesis of (E,E)-Cinnamylideneaceto-
phenones 3a–c,e,f,h–j: To a methanolic solution (200 mL) of the
appropriate acetophenone (42.9 mmol) sodium hydroxide (60%
aqueous solution, 200 mL) was slowly added. After cooling the
solution to room temperature, the appropriate cinnamaldehyde
(51.5 mmol) was added. The reaction mixture was stirred at room
temperature for 20 h and then poured into a mixture of water
(100 mL) and ice (100 g), and the pH was adjusted to 2 with dilute
hydrochloric acid. The precipitate obtained was filtered, taken up
in dichloromethane and purified by silica gel column chromatog-
raphy with a 1:1 mixture of light petroleum/dichloromethane as the
eluent. The solvent was removed in vacuo, and the residue was
recrystallised from ethanol to obtain cinnamylideneacetophenones
3a–c,e,f,h–j as yellow crystals. Products 3a,e,f,h–j were shown to
possess spectroscopic and analytical data identical to those pre-
viously reported.[32,33,53]
(E,E)-4Ј-Nitrocinnamylideneacetophenone (3g): Yield of 3.73 g
(52%). M.p. 91–93 °C (recrystallised from ethanol). 1H NMR
(300 MHz, CDCl3): δ = 7.00–7.12 (m, 3 H, α-H, γ-H and δ-H),
7.35–7.43 (m, 3 H, 3,4,5-H), 7.52 (dd, J = 7.9 and 1.6 Hz, 2 H, 2,6-
H), 7.65 (ddd, J = 14.9, 8.5 and 1.9 Hz, 1 H, β-H), 8.10 (d, J =
8.9 Hz, 2 H, 2Ј,6Ј-H), 8.34 (d, J = 8.9 Hz, 2 H, 3Ј,5Ј-H) ppm. 13C
NMR (75 MHz, CDCl3): δ = 123.8 (C-3Ј,5Ј), 124.4 (C-α), 126.4
(C-γ), 127.5 (C-2,6), 128.9 (C-3,5), 129.3 (C-2Ј,6Ј), 129.7 (C-4),
135.7 (C-1), 143.1 (C-1Ј), 143.6 (C-δ), 146.8 (C-β), 149.9 (C-4Ј),
188.9 (C=O) ppm. MS: m/z (%) = 279 (100) [M]+, 278 (35), 233
(10), 232 (19), 215 (10), 203 (15), 202 (30), 178 (7), 157 (16), 156
(8), 150 (13), 129 (51), 128 (46), 127 (25), 115 (16), 104 (18), 102
(10), 91 (11), 83 (8), 77 (19), 76 (21), 63 (13), 51 (15). C17H13NO3
(279.29): calcd. C 73.11, H 4.69, N 5.02; found C 72.94, H 4.68, N
5.10.
(E,E)-4-Methoxycinnamylideneacetophenone (3b): Yield of 6.57 g
(58%). M.p. 113–115 °C (recrystallised from ethanol). 1H NMR
(300 MHz, CDCl3): δ = 3.84 (s, 3 H, 4-OCH3), 6.86–7.01 (m, 2 H,
γ-H and δ-H), 6.90 (d, J = 8.8 Hz, 2 H, 2,6-H), 7.05 (d, J = 14.8 Hz,
1 H, α-H), 7.45 (d, J = 8.8 Hz, 2 H, 3,5-H), 7.48 (dd, J = 7.8 and
7.2 Hz, 2 H, 3Ј,5Ј-H), 7.55 (tt, J = 7.2 and 1.4 Hz, 1 H, 4Ј-H), 7.61
(dd, J = 14.8 and 9.8 Hz, 1 H, β-H). 7.97 (dd, J = 7.8 and 1.4 Hz,
2 H, 2Ј,6Ј-H) ppm. 13C NMR (75 MHz, CDCl3): δ = 55.3 (4-
OCH3), 114.2 (C-2,6), 124.3 (C-α), 124.8 (C-γ), 128.3 (C-2Ј,6Ј),
128.5 (C-3Ј,5Ј), 128.8 (C-3,5), 128.9 (C-1), 132.5 (C-4Ј), 138.4 (C-
1Ј), 141.8 (C-δ), 145.4 (C-β), 160.6 (C-4), 190.5 (C=O) ppm. MS:
m/z (%) = 264 (100) [M]+, 263 (18), 233 (19), 187 (10), 159 (27),
144 (22), 128 (17), 121 (13), 116 (17), 115 (34), 105 (30), 91 (9), 85
(11), 83 (16), 77 (37), 63 (10), 51 (22). C18H16O2 (264.32): calcd. C
81.79, H 6.10; found C 81.59, H 6.16.
General Procedure for the Epoxidation of (E,E)-Cinnamylideneace-
tophenones 3a–j with Hydrogen Peroxide as the Oxidant: H2O2
(30% aqueous solution, 0.17 mL, 5 mmol) was added to a solution
of the appropriate (E,E)-cinnamylideneacetophenone 3a–j
(0.5 mmol), 1-methylimidazole (0.03 mL, 0.35 mmol) and catalyst
(E,E)-4-Methylcinnamylideneacetophenone (3c): Yield of 6.17 g
(58%). M.p. 95–96 °C (recrystallised from ethanol). 1H NMR 4 (0.016 g, 0.025 mmol) in a 1:1 mixture of dichloromethane/meth-
Eur. J. Org. Chem. 2007, 2877–2887
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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2883

A. M. S. Silva et al.
anol (4 mL). The mixture was stirred at 40 °C for 4 h and then MS: m/z (%) = 266 (Ͻ1) [M]+, 250 (1), 237 (2), 207 (5), 174 (4),
FULL PAPER
diluted with dichloromethane (50 mL) and washed with water, and
the organic layer was separated and concentrated. The residue was
purified by preparative silica gel TLC (eluent: a 1:2 mixture of light
petroleum/dichloromethane), leading to the isolation of the unre-
acted starting materials 3a–j and the epoxidation products 5a,c–f,
6a,c–g, 7d, 8h,j, trans-9i,j and cis-9i,j. The yields in the epoxidation
of (E,E)-cinnamylideneacetophenones 3a–j were as follows: 5a
(21%), 6a (10%), 5c (13%), 5c (9%), 5d (9%), 6d (18%), 7d (7%),
5e (25%), 6e (11%), 5f (14%), 6f (7%), 6g (10%), 5h (11%), 8h
(14%), trans-9i (16%), cis-9i (26%), 8j (19%), trans-9j (13%) and
cis-9j (10%).
161 (25), 147 (12), 131 (11), 115 (13), 105 (100), 91 (62), 89 (12),
79 (13), 77 (68), 65 (6), 63 (7), 51 (23). HRMR-EI: calcd. For
C17H14O3 [M]+ 266.0943; found 266.0937.
(4R*,5R*)-4,5-Epoxy-5-(4-methylphenyl)-1-phenyl-2-penten-1-one
(5c): M.p. 101–102 °C. 1H NMR (300 MHz, CDCl3): δ = 2.36 (s, 3
H, 4-CH3), 3.59 (ddd, J = 6.4, 1.8 and 0.6 Hz, 1 H, γ-H), 3.86 (d,
J = 1.8 Hz, 1 H, δ-H), 6.95 (dd, J = 15.4 and 6.4 Hz, 1 H, β-H),
7.19 (d, J = 8.6 Hz, 2 H, 3,5-H), 7.21 (d, J = 8.6 Hz, 2 H, 2,6-H),
7.27 (dd, J = 15.4 and 0.6 Hz, 1 H, α-H), 7.49 (dd, J = 8.0 and
7.5 Hz, 2 H, 3Ј,5Ј-H), 7.59 (tt, J = 7.5 and 1.4 Hz, 1 H, 4Ј-H), 7.97
(dd, J = 8.0 and 1.4 Hz, 2 H, 2Ј,6Ј-H) ppm. 13C NMR (75 MHz,
CDCl3): δ = 21.2 (4-CH3), 61.1 (C-γ), 61.6 (C-δ), 125.5 (C-2,6),
127.0 (C-α), 128.6 (C-2Ј,6Ј), 128.7 (C-3Ј,5Ј), 129.3 (C-3,5), 133.0
(C-1), 133.1 (C-4Ј), 137.3 (C-1Ј), 138.6 (C-4), 143.7 (C-β), 189.5
(C=O) ppm. MS: m/z (%) = 264 (1) [M]+, 248 (1), 235 (4), 159 (3),
145 (15), 144 (100), 119 (8), 116 (15), 115 (37), 105 (21), 91 (11),
89 (3), 77 (26), 65 (4), 63 (2), 51 (7). HRMSEI: calcd. for C18H16O2
[M]+ 264.1150; found 264.1144.
General Procedure for the Epoxidation of (E,E)-Cinnamylideneace-
tophenones 3a–j with Iodosylbenzene as the Oxidant: Catalyst 4
(0.016 g, 0.025 mmol) was added to a solution of the appropriate
(E,E)-cinnamylideneacetophenone 3a–j (0.5 mmol) and pyridine N-
oxide (0.02 g, 0.25 mmol) in acetonitrile (4 mL). Then iodosylben-
zene (0.22 g, 1.0 mmol) was added, and the reaction mixture was
stirred at room temperature for 4 h and then concentrated and sub-
mitted to the same purification and isolation as described above
for the epoxidation with hydrogen peroxide. The yields in the epox-
idation of (E,E)-cinnamylideneacetophenones 3a–j were as follows:
5a (18%), 6a (43%), 5c (11%), 6c (23%), 5d (22%), 6d (33%), 7d
(39%), 5e (18%), 6e (41%), 5f (15%), 6f (55%), 6g (62%), 5h (4%),
8h (2%), trans-9i (60%), cis-9i (7%), 8j (13%), trans-9j (9%) and
cis-9j (3%).
Diastereomeric Mixture (56:44) of 2,3:4,5-Diepoxy-5-(4-meth-
ylphenyl)-1-phenylpentan-1-one (6c): M.p. 55–57 °C.
Diastereomer A. (2R*,3S*,4R*,5S*)-2,3:4,5-Diepoxy-5-(4-meth-
1
ylphenyl)-1-phenylpentan-1-one: H NMR (300 MHz, CDCl3): δ =
2.36 (s, 3 H, 4-CH3), 3.19 (dd, J = 4.6 and 2.0 Hz, 1 H, γ-H), 3.35
(dd, J = 4.6 and 1.9 Hz, 1 H, β-H), 3.90 (d, J = 2.0 Hz, 1 H, δ-H),
4.34 (d, J = 1.9 Hz, 1 H, α-H), 7.18–7.19 (m, 4 H, 2,3,5,6-H), 7.50–
7.55 (m, 2 H, 3Ј,5Ј-H), 7.63–7.69 (m, 1 H, 4Ј-H), 8.04–8.08 (m, 2
H, 2Ј,6Ј-H) ppm. 13C NMR (75 MHz, CDCl3): δ = 21.2 (4-CH3),
54.7 (C-α), 57.2 (C-δ), 57.8 (C-β), 59.6 (C-γ), 125.61 (C-2,6), 128.39
(C-2Ј,6Ј), 128.93 (C-3Ј,5Ј), 129.3 (C-3.5), 132.4 (C-1), 134.2 (C-4Ј),
135.2 (C-1Ј), 138.7 (C-4), 193.1 (C=O) ppm.
(4R*,5R*)-4,5-Epoxy-1,5-diphenyl-2-penten-1-one (5a): M.p. 68–
70 °C. 1H NMR (300 MHz, CDCl3): δ = 3.61 (dd, J = 6.6 and
1.8 Hz, 1 H, γ-H), 3.89 (d, J = 1.8 Hz, 1 H, δ-H), 6.95 (dd, J =
15.4 and 6.6 Hz, 1 H, β-H), 7.28 (d, J = 15.4 Hz, 1 H, α-H), 7.28–
7.42 (m, 5 H, 2,3,4,5,6-H), 7.50 (dd, J = 7.6 and 7.4 Hz, 2 H, 3Ј,5Ј-
H), 7.60 (tt, J = 7.4 and 1.6 Hz, 1 H, 4Ј-H), 7.97 (dd, J = 7.6 and
1.6 Hz, 2 H, 2Ј,6Ј-H) ppm. 13C NMR (75 MHz, CDCl3): δ = 61.2
(C-γ), 61.5 (C-δ), 125.5 (C-2,6), 127.2 (C-α), 128.6 (C-2Ј,6Ј), 128.66
(C-3,4,5), 128.69 (C-3,5Ј), 133.2 (C-4Ј), 136.1 (C-1), 137.3 (C-1Ј),
143.5 (C-β), 189.5 (C=O) ppm. MS: m/z (%) = 250 (3) [M]+, 234
(1), 221 (4), 159 (2), 145 (21), 144 (100), 115 (45), 105 (32), 89
(13), 77 (39), 63 (6), 51 (19). HRMS-EI: calcd. for C17H14O2 [M]+
250.0994; found 250.0986.
Diastereomer B. (2R*,3S*,4S*,5R*)-2,3:4,5-Diepoxy-5-(4-meth-
1
ylphenyl)-1-phenylpentan-1-one: H NMR (300 MHz, CDCl3): δ =
2.36 (s, 3 H, 4-CH3), 3.28 (dd, J = 3.0 and 2.0 Hz, 1 H, γ-H), 3.46
(dd, J = 3.0 and 2.0 Hz, 1 H, β-H), 3.93 (d, J = 2.0 Hz, 1 H, δ-H),
4.36 (d, J = 2.0 Hz, 1 H, α-H), 7.18–7.19 (m, 4 H, 2,3,5,6-H), 7.50–
7.55 (m, 2 H, 3Ј,5Ј-H), 7.63–7.69 (m, 1 H, 4Ј-H), 8.04–8.08 (m, 2
H, 2Ј,6Ј-H) ppm. 13C NMR (75 MHz, CDCl3): δ = 21.2 (4-CH3),
54.2 (C-α), 56.3 (C-δ), 56.5 (C-β), 58.6 (C-γ), 125.64 (C-2,6), 128.43
(C-2Ј,6Ј), 128.91 (C-3Ј,5Ј), 129.3 (C-3,5), 132.6 (C-1), 134.2 (C-4Ј),
135.2 (C-1Ј), 138.6 (C-4), 193.3 (C=O) ppm.
Diastereomeric Mixture (58:42) of 2,3:4,5-Diepoxy-1,5-diphenyl-
pentan-1-one (6a): Yellow oil.
MS: m/z (%) = 280 (1) [M]+, 265 (2), 251 (5), 221 (4), 207 (8), 175
(40), 160 (5), 145 (5), 131 (9), 121 (5), 115 (5), 119 (20), 106 (15),
105 (100), 91 (18), 77 (33), 65 (6), 51 (10). HRMS-EI: calcd. for
C18H16O3 [M]+ 280.1099; found 280.1103.
Diastereomer
A.
(2R*,3S*,4R*,5S*)-2,3:4,5-Diepoxy-1,5-di-
1
phenylpentan-1-one: H NMR (300 MHz, CDCl3): δ = 3.18 (dd, J
= 4.6 and 1.9 Hz, 1 H, γ-H), 3.35 (dd, J = 4.6 and 1.9 Hz, 1 H, β-
H), 3.93 (d, J = 1.9 Hz, 1 H, δ-H), 4.34 (d, J = 1.9 Hz, 1 H, α-H),
7.26–7.39 (m, 5 H, 2,3,4,5,6-H), 7.52 (t, J = 7.4 Hz, 2 H, 3Ј,5Ј-H),
7.65 (t, J = 7.4 Hz, 1 H, 4Ј-H), 8.05 (dd, J = 7.4 and 1.2 Hz, 2 H,
2Ј,6Ј-H) ppm. 13C NMR (75 MHz, CDCl3): δ = 54.7 (C-α), 57.3
(C-δ), 57.7 (C-β), 59.8 (C-γ), 125.66 (C-2,6), 128.4 (C-2Ј,6Ј), 128.69
(C-3,5), 128.80 (C-4), 128.99 (C-3Ј,5Ј), 134.2 (C-4Ј), 135.3 (C-1Ј),
135.5 (C-1), 193.1 (C=O) ppm.
(4R*,5R*)-4,5-Epoxy-5-(4-nitrophenyl)-1-phenyl-2-penten-1-one
1
(5d): M.p. 99–101 °C. H NMR (300 MHz, CDCl3): δ = 3.61 (ddd,
J = 6.6, 1.7 and 0.6 Hz, 1 H, γ-H), 4.01 (d, J = 1.7 Hz, 1 H, δ-H),
6.93 (dd, J = 15.4 and 6.6 Hz, 1 H, β-H), 7.33 (d, J = 15.4 Hz, 1
H, α-H), 7.50 (d, J = 8.8 Hz, 2 H, 2,6-H), 7.51 (dd, J = 7.8 and
7.2 Hz, 2 H, 3Ј,5Ј-H), 7.61 (tt, J = 7.2 and 1.5 Hz, 1 H, 4Ј-H), 7.98
(dd, J = 7.8 and 1.5 Hz, 2 H, 2Ј,6Ј-H), 8.26 (d, J = 8.8 Hz, 2 H,
3,5-H) ppm. 13C NMR (75 MHz, CDCl3): δ = 60.2 (C-δ), 61.5 (C-
γ), 123.9 (C-3,5), 126.3 (C-2,6), 128.0 (C-α), 128.6 (C-2Ј,6Ј), 128.8
(C-3Ј,5Ј), 133.4 (C-4Ј), 137.0 (C-1Ј), 142.1 (C-β), 143.4 (C-1), 148.0
(C-4), 189.1 (C=O) ppm. MS: m/z (%) = 295 (Ͻ1) [M]+, 266 (2),
190 (1), 145 (16), 144 (100), 116 (15), 115 (42), 105 (23), 89 (5), 77
(23), 63 (3), 51 (4). HRMS-EI: C17H13NO4 [M]+ 295.0845; found
295.0854.
Diastereomer B. (2R*,3S*,4S*,5R*)-2,3:4,5-Diepoxy-1,5-diphenyl-
pentan-1-one: H NMR (300 MHz, CDCl3): δ = 3.28 (dd, J = 3.0
1
and 2.0 Hz, 1 H, γ-H), 3.46 (dd, J = 3.0 and 2.0 Hz, 1 H, β-H),
3.96 (d, J = 2.0 Hz, 1 H, δ-H), 4.36 (d, J = 2.0 Hz, 1 H, α-H),
7.26–7.39 (m, 5 H, 2,3,4,5,6-H), 7.52 (t, J = 7.4 Hz, 2 H, 3Ј,5Ј-H),
7.65 (t, J = 7.4 Hz, 1 H, 4Ј-H), 8.05 (dd, J = 7.4 and 1.2 Hz, 2 H,
2Ј,6Ј-H) ppm. 13C NMR (75 MHz, CDCl3): δ = 54.2 (C-α), 56.3
(C-δ), 56.5 (C-β), 58.8 (C-γ), 125.70 (C-2,6), 128.5 (C-2Ј,6Ј), 128.69
(C-3,5), 128.74 (C-4), 128.96 (C-3Ј,5Ј), 134.2 (C-4Ј), 135.3 (C-1Ј), Diastereomeric Mixture (50:50) of 2,3:4,5-Diepoxy-5-(4-ni-
135.8 (C-1), 193.3 (C=O) ppm. trophenyl)-1-phenylpentan-1-one (6d): M.p. 122–124 °C.
2884
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© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2007, 2877–2887

Epoxidation of Cinnamylideneacetophenones
FULL PAPER
Diastereomer A. (2R*,3S*,4R*,5S*)-2,3:4,5-Diepoxy-5-(4-ni-
trophenyl)-1-phenylpentan-1-one: 1H NMR (300 MHz, CDCl3): δ =
3.17 (dd, J = 4.8 and 1.8 Hz, 1 H, γ-H), 3.38 (dd, J = 4.8 and
H, δ-H), 4.29 (d, J = 2.0 Hz, 1 H, α-H), 6.97 (d, J = 8.9 Hz, 2 H,
3Ј,5Ј-H), 7.26–7.30 (m, 2 H, 2,6-H), 7.33–7.36 (m, 3 H, 3,4,5-H),
8.04 (d, J = 8.9 Hz, 2 H, 2Ј,6Ј-H) ppm. 13C NMR (75 MHz,
2.0 Hz, 1 H, β-H), 4.06 (d, J = 1.8 Hz, 1 H, δ-H), 4.36 (d, J = CDCl3): δ = 54.4 (C-α), 55.5 (4Ј-OCH3), 57.1 (C-δ), 57.4 (C-β),
2.0 Hz, 1 H, α-H), 7.48 (d, J = 8.8 Hz, 2 H, 2,6-H), 7.54 (t, J = 59.7 (C-γ), 114.1 (C-3Ј,5Ј), 125.57 (C-2,6), 128.32 (C-1Ј), 128.5 (C-
7.7 Hz, 2 H, 3Ј,5Ј-H), 7.67 (tt, J = 7.4 and 1.5 Hz, 1 H, 4Ј-H), 8.04–
3,5), 128.57 (C-4), 130.75 (C-2Ј,6Ј), 135.5 (C-1), 164.3 (C-4Ј), 191.2
8.09 (m, 2 H, 2Ј,6Ј-H), 8.24 (d, J = 8.8 Hz, 2 H, 3,5-H) ppm. 13C (C=O) ppm.
NMR (75 MHz, CDCl3): δ = 54.7 (C-α), 56.1 (C-δ), 57.2 (C-β),
Diastereomer B. (2R*,3S*,4S*,5R*)-2,3:4,5-Diepoxy-1-(4-meth-
60.4 (C-γ), 123.9 (C-3,5), 126.4 (C-2,6), 128.44 (C-2Ј,6Ј), 128.98 (C-
3Ј,5Ј), 134.4 (C-4Ј), 135.1 (C-1Ј), 143.2 (C-1), 148.1 (C-4), 192.9
(C=O) ppm.
oxyphenyl)-5-phenylpentan-1-one: 1H NMR (300 MHz, CDCl3): δ
= 3.26 (dd, J = 3.2 and 2.0 Hz, 1 H, γ-H), 3.44 (dd, J = 3.2 and
2.0 Hz, 1 H, β-H), 3.88 (s, 3 H, 4Ј-OCH3), 3.94 (d, J = 2.0 Hz, 1
H, δ-H), 4.30 (d, J = 2.0 Hz, 1 H, α-H), 6.98 (d, J = 8,9 Hz, 2 H,
3Ј,5Ј-H), 7.26–7.30 (m, 2 H, 2,6-H), 7.33–7.36 (m, 3 H, 3,4,5-H),
8.05 (d, J = 8.9 Hz, 2 H, 2Ј,6Ј-H) ppm. 13C NMR (75 MHz,
CDCl3): δ = 53.9 (C-α), 55.5 (4Ј-OCH3), 56.2 (C-δ), 56.3 (C-β),
58.8 (C-γ), 114.0 (C-3Ј,5Ј), 125.60 (C-2,6), 128.28 (C-1Ј), 128.5 (C-
3,5), 128.62 (C-4), 130.79 (C-2Ј,6Ј), 135.7 (C-1), 164.3 (C-4Ј), 191.4
(C=O) ppm.
Diastereomer B. (2R*,3S*,4S*,5R*)-2,3:4,5-Diepoxy-5-(4-ni-
trophenyl)-1-phenylpentan-1-one: 1H NMR (300 MHz, CDCl3): δ =
3.32 (dd, J = 2.6 and 1.9 Hz, 1 H, γ-H), 3.54 (dd, J = 2.6 and
2.0 Hz, 1 H, β-H), 4.08 (d, J = 1.9 Hz, 1 H, δ-H), 4.39 (d, J =
2.0 Hz, 1 H, α-H), 7.48 (d, J = 8.8 Hz, 2 H, 2,6-H), 7.54 (t, J =
7.7 Hz, 2 H, 3Ј,5Ј-H), 7.67 (tt, J = 7.4 and 1.5 Hz, 1 H, 4Ј-H), 8.04–
8.09 (m, 2 H, 2Ј,6Ј-H), 8.24 (d, J = 8.8 Hz, 2 H, 3,5-H) ppm. 13C
NMR (75 MHz, CDCl3): δ = 54.1 (C-α), 55.3 (C-δ), 55.8 (C-β),
59.1 (C-γ), 123.9 (C-3,5), 126.4 (C-2,6), 128.40 (C-2Ј,6Ј), 128.96 (C-
3Ј,5Ј), 134.3 (C-4Ј), 135.2 (C-1Ј), 142.9 (C-1), 148.0 (C-4), 192.7
(C=O) ppm.
MS: m/z (%) = 296 (1) [M]+, 280 (2), 238 (3), 209 (2), 190 (3), 174
(3), 161 (11), 147 (2), 136 (16), 135 (100), 131 (3), 121 (4), 115 (4),
107 (11), 105 (13), 92 (10), 91 (28), 79 (9), 77 (31), 65 (5), 51 (9).
HRMS-EI: C18H16O3 [M]+ 296.1049; found 296.1049.
MS: m/z (%) = 311 (1) [M]+, 282 (2), 266 (1), 254 (2), 206 (7), 160
(7), 136 (8), 131 (5), 115 (5), 106 (14), 105 (100), 91 (4), 89 (8), 78
(9), 77 (50), 65 (3), 63 (5), 51 (13). HRMS-EI: C17H13NO5 [M]+
311.0794; found 311.0780.
(4R*,5R*)-4,5-Epoxy-1-(4-methylphenyl)-5-phenyl-2-penten-1-one
1
(5f): Yellowish oil. H NMR (300 MHz, CDCl3): δ = 2.43 (s, 3 H,
4Ј-CH3), 3.60 (ddd, J = 6.5, 1.6 and 0.5 Hz, 1 H, γ-H), 3.89 (d, J
= 1.6 Hz, 1 H, δ-H), 6.93 (dd, J = 15.4 and 6.5 Hz, 1 H, β-H),
7.25–7.41 (m, 8 H, α-H, 2,3,4,5,6-H and 3Ј,5Ј-H), 7.89 (dd, J = 6.5
and 1.7 Hz, 2 H, 2Ј,6Ј-H) ppm. 13C NMR (75 MHz, CDCl3): δ =
21.7 (4Ј-CH3), 61.2 (C-γ), 61.4 (C-δ), 125.5 (C-2,6), 127.2 (C-α),
128.6 (C-3,4,5), 128.7 (C-2Ј,6Ј), 129.4 (C-3Ј,5Ј), 134.7 (C-1Ј), 136.2
(C-1), 143.0 (C-β), 144.1 (C-4Ј), 188.9 (C=O) ppm. MS: m/z (%) =
264 (1) [M]+, 248 (2), 235 (6), 173 (2), 159 (19), 158 (100), 157 (9),
145 (3), 129 (28), 119 (26), 115 (21), 105 (9), 91 (25), 89 (10), 77
(11), 65 (11), 63 (6), 51 (6). HRMS-EI: C18H16O2 [M]+ 264.1150;
found 264.1143.
(2R*,3S*)-2,3-Epoxy-5-(4-nitrophenyl)-1-phenyl-4-penten-1-one
(7d): M.p. 111–113 °C. 1H NMR (300 MHz, CDCl3): δ = 3.79 (dd,
J = 7.7 and 1.8 Hz, 1 H, β-H), 4.36 (d, J = 1.8 Hz, 1 H, α-H), 6.26
(dd, J = 16.0 and 7.7 Hz, 1 H, γ-H), 6.96 (d, J = 16.0 Hz, 1 H, δ-
H), 7.53 (dd, J = 8.2 and 7.6 Hz, 2 H, 3Ј,5Ј-H), 7.56 (d, J = 8.8 Hz,
2 H, 2,6-H), 7.65 (tt, J = 7.6 and 1.4 Hz, 1 H, 4Ј-H), 8.04 (dd, J =
7.2 and 1.4 Hz, 2 H, 2Ј,6Ј-H), 8.21 (d, J = 8.8 Hz, 2 H, 3,5-H) ppm.
13C NMR (75 MHz, CDCl3): δ = 58.2 (C-β), 58.8 (C-α), 124.1 (C-
3,5), 127.2 (C-2,6), 128.3 (C-2Ј,6Ј), 128.9 (C-3Ј,5Ј), 129.3 (C-γ),
133.7 (C-δ), 134.2 (C-4Ј), 135.3 (C-1Ј), 141.7 (C-1), 147.4 (C-4),
193.0 (C=O) ppm. MS: m/z (%) = 295 (1) [M]+, 267 (8), 266 (39),
238 (4), 220 (8), 192 (9), 160 (5), 151 (5), 144 (6), 116 (11), 115
(30), 106 (12), 105 (100), 90 (10), 89 (15), 85 (12), 83 (17), 78 (8),
77 (64), 65 (5), 63 (8), 51 (17). HRMS-EI: C17H13NO4 [M]+
295.0845; found 295.0854.
Diastereomeric Mixture (53:47) of 2,3:4,5-Diepoxy-1-(4-meth-
ylphenyl)-5-phenylpentan-1-one (6f): Yellowish oil.
Diastereomer A. (2R*,3S*,4R*,5S*)-2,3:4,5-Diepoxy-1-(4-meth-
1
ylphenyl)-5-phenylpentan-1-one: H NMR (300 MHz, CDCl3): δ =
2.45 (s, 3 H, 4Ј-CH3), 3.19 (dd, J = 4.6 and 2.0 Hz 1 H, γ-H), 3.35
(dd, J = 4.6 and 2.0 Hz, 1 H, β-H), 3.93 (d, J = 2.0 Hz, 1 H, δ-H),
4.33 (d, J = 2.0 Hz, 1 H, α-H), 7.28–7.38 (m, 7 H, 2,3,4,5,6-H and
3Ј,5Ј-H), 7.96 (d, J = 8.3 Hz, 2 H, 2Ј,6Ј-H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 21.7 (4Ј-CH3), 54.6 (C-α), 57.2 (C-δ), 57.6
(C-β), 59.8 (C-γ), 125.6 (C-2,6), 128.41 (C-2Ј,6Ј), 129.63 (C-3Ј,5Ј),
128.52 (C-3,4,5), 132.8 (C-1Ј), 135.5 (C-1), 145.3 (C-4Ј), 192.6
(C=O) ppm.
(4R*,5R*)-4,5-Epoxy-1-(4-methoxyphenyl)-5-phenyl-2-penten-1-one
1
(5e): M.p. 67–69 °C. H NMR (300 MHz, CDCl3): δ = 3.59 (ddd,
J = 6.5, 1.9 and 0.7 Hz, 1 H, γ-H), 3.88 (s, 3 H, 4Ј-OCH3), 3.89 (d,
J = 1.9 Hz, 1 H, δ-H), 6.92 (dd, J = 15.3 and 6.5 Hz, 1 H, β-H),
6.97 (d, J = 9.0 Hz, 2 H, 3Ј,5Ј-H), 7.28 (d, J = 15.3 Hz, 1 H, α-H),
7.30–7.33 (m, 2 H, 2,6-H), 7.34–7.39 (m, 3 H, 3,4,5-H), 7.98 (d, J
= 9.0 Hz, 2 H, 2Ј,6Ј-H) ppm. 13C NMR (75 MHz, CDCl3): δ =
55.5 (C-δ), 61.3 (C-γ), 61.5 (4Ј-OCH3), 113.9 (C-3Ј,5Ј), 125.5 (C-
2,6), 127.0 (C-α), 128.6 (C-3,4,5), 130.2 (C-1Ј), 131.0 (C-2Ј,6Ј),
136.2 (C-1), 142.5 (C-β), 163.7 (C-4Ј), 187.7 (C=O) ppm. MS: m/z
(%) = 280 (4) [M]+, 264 (2), 263 (2), 251 (8), 189 (3), 175 (19), 174
(100), 160 (6), 159 (43), 145 (8), 135 (58), 131 (17), 121 (3), 115 (9),
107 (6), 105 (16), 92 (17), 89 (10), 77 (34), 63 (8), 57 (3), 51 (1).
HRMS-EI: C18H16O3 [M]+ 280.1099; found 280.1095.
Diastereomer B. (2R*,3S*,4S*,5R*)-2,3:4,5-Diepoxy-1-(4-meth-
1
ylphenyl)-5-phenylpentan-1-one: H NMR (300 MHz, CDCl3): δ =
2.45 (s, 3 H, 4Ј-CH3), 3.28 (dd, J = 3.1 and 2.0 Hz, 1 H, γ-H), 3.46
(dd, J = 3.1 and 2.0 Hz, 1 H, β-H), 3.96 (d, J = 2.0 Hz, 1 H, δ-H),
4.35 (d, J = 2.0 Hz, 1 H, α-H), 7.28–7.38 (m, 7 H, 2,3,4,5,6-H and
3Ј,5Ј-H), 7.97 (d, J = 8.3 Hz, 2 H, 2Ј,6Ј-H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 21.7 (4Ј-CH3), 54.0 (C-α), 56.3 (C-δ), 56.4
(C-β), 58.8 (C-γ), 125.7 (C-2,6), 128.45 (C-2Ј,6Ј), 128.62 (C-3Ј,5Ј),
128.54 (C-4), 128.61 (C-3,5), 132.8 (C-1Ј), 135.8 (C-1), 145.3 (C-
4Ј), 192.8 (C=O) ppm.
Diastereomeric Mixture (52:48) of 2,3:4,5-Diepoxy-1-(4-meth-
oxyphenyl)-5-phenylpentan-1-one (6e): Yellowish oil.
Diastereomer A. (2R*,3S*,4R*,5S*)-2,3:4,5-Diepoxy-1-(4-meth-
oxyphenyl)-5-phenylpentan-1-one: 1H NMR (300 MHz, CDCl3): δ
= 3.18 (dd, J = 4.5 and 2.0 Hz, 1 H, γ-H), 3.34 (dd, J = 4.5 and
1.9 Hz, 1 H, β-H), 3.88 (s, 3 H, 4Ј-OCH3), 3.91 (d, J = 1.9 Hz, 1
MS: m/z (%) = 280 (Ͻ1) [M]+, 251 (2), 221 (3), 193 (1), 174 (3),
161 (18), 131 (6), 119 (100), 105 (12), 91 (63), 79 (6), 77 (10), 65
(11), 51 (3). HRMS-EI: C18H16O3 [M]+ 280.1099; found 280.1090.
Eur. J. Org. Chem. 2007, 2877–2887
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
2885

A. M. S. Silva et al.
FULL PAPER
Diastereomeric Mixture (47:53) of 2,3:4,5-Diepoxy-1-(4-ni-
trophenyl)-5-phenylpentan-1-one (6g): Yellowish oil.
7.22 (d, J = 15.4 Hz, 1 H, α-H), 7.30–7.42 (m, 5 H, 2,3,4,5,6-H),
7.49 (dd, J = 7.9 and 7.4 Hz, 2 H, 3Ј,5Ј-H), 7.59 (tt, J = 7.4 and
1.6 Hz, 1 H, 4Ј-H), 7.99 (dd, J = 7.9 and 1.6 Hz, 2 H, 2Ј,6Ј-H)
ppm. 13C NMR (75 MHz, CDCl3): δ = 14.9 (γ-CH3), 61.8 (C-γ),
66.7 (C-δ), 125.0 (C-α), 126.6 (C-2,6), 128.0 (C-4), 128.2 (C-3,5),
128.60 (C-3Ј,5Ј), 128.64 (C-2Ј,6Ј), 133.1 (C-4Ј), 134.7 (C-1), 137.5
(C-1Ј), 148.9 (C-β), 189.9 (C=O) ppm. MS: m/z (%) = 264 (1)
[M]+, 249 (2), 221 (4), 158 (100), 145 (2), 144 (2), 131 (4), 129 (7),
115 (16), 105 (47), 91 (5), 89 (6), 77 (4), 65 (2), 63 (3), 53 (23), 51
(26). HRMS-EI: C18H16O2 [M]+ 264.1150; found 264.1141.
Diastereomer A. (2R*,3S*,4R*,5S*)-2,3:4,5-Diepoxy-1-(4-ni-
trophenyl)-5-phenylpentan-1-one: 1H NMR (300 MHz, CDCl3): δ =
3.20 (dd, J = 4.6 and 1.9 Hz, 1 H, γ-H), 3.39 (dd, J = 4.6 and
1.9 Hz, 1 H, β-H), 3.94 (d, J = 1.9 Hz, 1 H, δ-H), 4.31 (d, J =
1.9 Hz, 1 H, α-H), 7.26–7.30 (m, 2 H, 2,6-H), 7.34–7.38 (d, 3 H,
3,4,5-H), 8.21 (d, J = 8.8 Hz, 2 H, 2Ј,6Ј-H), 8.34 (d, J = 8.8 Hz, 2
H, 3Ј,5Ј-H) ppm. 13C NMR (75 MHz, CDCl3): δ = 55.1 (C-α), 57.2
(C-δ), 57.8 (C-β), 59.4 (C-γ), 123.99 (C-3Ј,5Ј), 125.57 (C-2,6), 128.6
(C-3,5), 128.82 (C-4), 129.56 (C-2Ј,6Ј), 135.1 (C-1), 139.3 (C-1Ј), (E,4R*,5S*)-4,5-Epoxy-4-methyl-1,5-diphenyl-2-penten-1-one (cis-
1
150.7 (C-4Ј), 192.5 (C=O) ppm.
9i): Yellowish oil. H NMR (300 MHz, CDCl3): δ = 1.72 (s, 3 H,
γ-CH3), 4.22 (s, 1 H, δ-H), 6.59 (d, J = 15.8 Hz, 1 H, β-H), 6.96
(d, J = 15.8 Hz, 1 H, α-H), 7.25–7.35 (m, 5 H, 2,3,4,5,6-H), 7,38
(dd, J = 8.2 and 8.0 Hz, 2 H, 3Ј,5Ј-H), 7.51 (t, J = 8.0 and 1.3 Hz,
1 H, 4Ј-H), 7.68 (dd, J = 8.2 and 1.3 Hz, 2 H, 2Ј,6Ј-H) ppm. 13C
NMR (75 MHz, CDCl3): δ = 21.1 (γ-CH3), 62.4 (C-γ), 66.6 (C-δ),
126.5 (C-2,6), 127.9 (C-3,5), 128.2 (C-α), 128.4 (C-4), 128.5 (C-
3Ј,5Ј), 128.6 (C-2Ј,6Ј), 132.8 (C-4Ј), 134.6 (C-1), 137.3 (C-1Ј), 144.7
(C-β), 190.3 (C=O) ppm. MS: m/z (%) = 264 (1) [M]+, 251 (2), 207
(10), 175 (31), 158 (18), 145 (5), 131 (12), 115 (7), 105 (100), 91
(57), 77 (66), 65 (3), 63 (5), 53 (3), 51 (22). HRMS-EI: C18H16O2
[M]+ 264.1150; found 264.1138.
Diastereomer B. (2R*,3S*,4S*,5R*)-2,3:4,5-Diepoxy-1-(4-ni-
trophenyl)-5-phenylpentan-1-one: 1H NMR (300 MHz, CDCl3): δ =
3.31 (dd, J = 2.9 and 1.9 Hz, 1 H, γ-H), 3.51 (dd, J = 2.9 and
2.0 Hz, 1 H, β-H), 3.96 (d, J = 1.9 Hz, 1 H, δ-H), 4.34 (d, J =
2.0 Hz, 1 H, α-H), 7.26–7.30 (m, 2 H, 2,6-H), 7.34–7.38 (d, 3 H,
3,4,5-H), 8.22 (d, J = 8.9 Hz, 2 H, 2Ј,6Ј-HЈ), 8.34 (d, J = 8.9 Hz, 2
H, 3Ј,5Ј-H) ppm. 13C NMR (75 MHz, CDCl3): δ = 54.6 (C-α), 56.4
(C-δ), 56.6 (C-β), 58.3 (C-γ), 123.97 (C-3Ј,5Ј), 125.60 (C-2,6), 128.6
(C-3,5), 128.76 (C-4), 129.58 (C-2Ј,6Ј), 135.4 (C-1), 139.3 (C-1Ј),
150.7 (C-4Ј), 192.4 (C=O) ppm.
MS: m/z (%) = 311 (1) [M]+, 282 (3), 252 (14), 205 (6), 174 (56),
161 (75), 159 (26), 150 (40), 135 (22), 131 (21), 121 (2), 115 (12),
105 (38), 104 (25), 92 (24), 91 (100), 79 (25), 77 (39), 76 (18), 65
(9), 55 (77), 51 (11). HRMS-EI: C17H13NO5 [M]+ 311.0794; found
311.0787.
(E,2R*,3S*)-3-Hydroxy-α-methyl-2-styryl-4-chromanone (8j): M.p.
122–123 °C. 1H NMR (300 MHz, CDCl3): δ = 2.14 (s, 3 H, α-CH3),
3.70 (br. s, 1 H, 3-OH), 4.60–4.71 (m, 2 H, 2,3-H), 6.75 (d, J =
1.1 Hz, 1 H, β-H), 7.04 (d, J = 8.0 Hz, 1 H, 8-H), 7.08 (dt, J = 7.8
and 0.8 Hz, 1 H, 6-H), 7.25–7.40 (m, 5 H, 2Ј,3Ј,4Ј,5Ј,6Ј-H), 7.55
(dt, J = 8.0 and 1.6 Hz, 1 H, 7-H), 7.90 (dd, J = 7.8 and 1.6 Hz, 1
H, 5-H) ppm. 13C NMR (75 MHz, CDCl3): δ = 13.3 (γ-CH3), 71.1
(C-3), 88.0 (C-2), 118.1 (C-8), 118.4 (C-10), 121.9 (C-6), 127.2 (C-
4Ј), 127.2 (C-5), 128.2 (C-3Ј,5Ј), 129.3 (C-2Ј,6Ј), 132.4 (C-β), 132.6
(C-α), 136.6 (C-1Ј), 136.8 (C-7), 161.9 (C-9), 194.8 (C-4) ppm. MS:
m/z (%) = 280 (52) [M]+, 278 (13), 263 (9), 251 (31), 223 (6), 207
(10), 201 (5), 174 (10), 160 (26), 159 (90), 145 (35), 131 (32), 121
(100), 115 (38), 105 (21), 92 (29), 91 (95), 82 (9), 77 (28), 65 (25),
63 (18), 57 (9), 51 (16). HRMS-EI: C18H16O3 [M]+ 280.1099; found
280.0986.
(4R*,5R*)-4,5-Epoxy-1-(2-hydroxyphenyl)-5-phenyl-2-penten-1-one
1
(5h): M.p. 75–77 °C. H NMR (300 MHz, CDCl3): δ = 3.63 (ddd,
J = 6.2, 1.8 and 0.7 Hz, 1 H, γ-H), 3.90 (d, J = 1.8 Hz, 1 H, δ-H),
6.93 (ddd, J = 7.9, 7.8 and 1.0 Hz, 1 H, 5Ј-H), 7.02 (dd, J = 8.1
and 1.0 Hz, 1 H, 3Ј-H), 7.09 (dd, J = 15.1 and 6.2 Hz, 1 H, β-H),
7.31–7.34 (m, 2 H, 2,6-H), 7.35–7.40 (m, 3 H, 3,4,5-H), 7.40 (d, J
= 15.1 Hz, 1 H, α-H), 7.51 (ddd, J = 8.1, 7.8 and 1.6 Hz, 1 H, 4Ј-
H), 7.82 (dd, J = 7.9 and 1.6 Hz, 1 H, 6Ј-H), 12.55 (s, 1 H, 2Ј-OH)
ppm. 13C NMR (75 MHz, CDCl3): δ = 61.0 (C-γ), 61.8 (C-δ), 118.6
(C-3Ј), 119.0 (C-5Ј), 119.4 (C-1Ј), 125.3 (C-α), 125.5 (C-2,6), 128.7
(C-3,5), 128.8 (C-4), 129.9 (C-6Ј), 135.9 (C-1), 136.8 (C-4Ј), 144.2
(C-β), 163.6 (C-2Ј), 193.0 (C=O) ppm. MS: m/z (%) = 266 (3)
[M]+, 250 (13), 237 (4), 161 (17), 160 (100), 145 (8), 131 (62), 121
(32), 115 (7), 105 (9), 91 (8), 89 (9), 78 (18), 77 (18), 65 (17), 63 (7),
53 (2), 51 (8). HRMS-EI: C17H14O3 [M]+ 266.0943; found
266.0940.
(E,4R*,5R*)-4,5-Epoxy-1-(2-hydroxyphenyl)-4-methyl-5-phenyl-2-
penten-1-one (trans-9j): M.p. 54–55 °C. 1H NMR (300 MHz,
CDCl3): δ = 1.33 (s, 3 H, γ-CH3), 4.06 (s, 1 H, δ-H), 6.93 (ddd, J
= 8.0, 7.9 and 1.0 Hz, 1 H, 5Ј-H), 7.02 (dd, J = 8.1 and 1.0 Hz, 1
H, 3Ј-H), 7.19 (d, J = 15.2 Hz, 1 H, β-H), 7.34 (d, J = 15.2 Hz, 1
H, α-H), 7.32–7.42 (m, 5 H, 2,3,4,5,6-H), 7.50 (ddd, J = 8.1, 7.9
and 1.6 Hz, 1 H, 4Ј-H), 7.85 (dd, J = 8.0 and 1.6 Hz, 2 H, 6Ј-H),
12.60 (s, 1 H, 2Ј-OH) ppm. 13C NMR (75 MHz, CDCl3): δ = 14.9
(γ-CH3), 61.9 (C-γ), 67.0 (C-δ), 118.6 (C-3Ј), 118.9 (C-5Ј), 119.5
(C-1Ј), 123.3 (C-α), 126.6 (C-2,6), 128.1 (C-4), 128.3 (C-3,5), 130.0
(C-6Ј), 134.5 (C-1), 137.0 (C-4Ј), 149.6 (C-β), 163.6 (C-2Ј), 193.5
(C=O) ppm. MS: m/z (%) = 280 (1) [M]+, 264 (2), 237 (3), 174
(100), 159 (37), 147 (7), 145 (6), 131 (53), 121 (38), 115 (8), 105
(11), 93 (12), 91 (10), 77 (20), 65 (24), 53 (19), 51 (11). HRMS-EI:
C18H16O3 [M]+ 280.1099; found 280.1093.
(E,2R*,3S*)-3-Hydroxy-2-styryl-4-chromanone (8h): M.p. 159–
161 °C. 1H NMR (300 MHz, CDCl3): δ = 3.72 (d, J = 1.2 Hz, 1
H, 3-OH), 4.43 (d, J = 12.2 Hz, 1 H, 3-H), 4.80 (ddd, J = 12.2, 6.4
and 1.2 Hz, 1 H, 2-H), 6.52 (dd, J = 16.0 and 6.4 Hz, 1 H, α-H),
6.95 (d, J = 16.0 Hz, 1 H, β-H), 7.07 (d, J = 8.1 Hz, 1 H, 8-H),
7.09 (dt, J = 7.6 and 1.0 Hz, 1 H, 6-H), 7.26–7.38 (m, 3 H, 3Ј,4Ј,5Ј-
H), 7.49 (dd, J = 8.2 and 1.3 Hz, 2 H, 2Ј,6Ј-H), 7.56 (dt, J = 8.1
and 1.7 Hz, 1 H, 7-H), 7.90 (dd, J = 7.6 and 1.7 Hz, 1 H, 5-H)
ppm. 13C NMR (75 MHz, CDCl3): δ = 73.1 (C-3), 82.3 (C-2), 118.1
(C-8), 118.5 (C-10), 122.0 (C-6), 124.0 (C-α), 126.9 (C-2Ј,6Ј), 127.3
(C-5), 128.4 (C-4Ј), 128.6 (C-3Ј,5Ј), 134.9 (C-β), 135.9 (C-1Ј), 136.9
(C-7), 161.5 (C-9), 194.1 (C-4) ppm. MS: m/z (%) = 266 (43) [M]+,
237 (24), 209 (12), 146 (35), 145 (37), 131 (13), 121 (100), 117 (24),
115 (35), 105 (7), 92 (27), 91 (35), 77 (19), 71 (14), 65 (13), 57 (19),
51 (10). HRMS-EI: C17H16O3 [M]+ 280.0943; found 280.0941.
(E,4R*,5S*)-4,5-Epoxy-1-(2-hydroxyphenyl)-4-methyl-5-phenyl-2-
penten-1-one (cis-9j): M.p. 54–55 °C. 1H NMR (300 MHz, CDCl3):
δ = 1.74 (s, 3 H, γ-CH3), 4.24 (s, 1 H, δ-H), 6.75 (d, J = 15.4 Hz,
1 H, β-H), 6.86 (ddd, J = 7.9, 7.8 and 1.0 Hz, 1 H, 5Ј-H), 6.95 (dd,
J = 8.1 and 1.0 Hz, 1 H, 3Ј-H), 7.13 (d, J = 15.4 Hz, 1 H, α-H),
7.27–7.35 (m, 5 H, 2,3,4,5,6-H), 7.46 (ddd, J = 8.1, 7.8 and 1.6 Hz,
(E,4R*,5R*)-4,5-Epoxy-4-methyl-1,5-diphenyl-2-penten-1-one 1 H, 4Ј-H), 7.60 (dd, J = 7.9 and 1.6 Hz, 2 H, 6Ј-H), 12.38 (s, 1 H,
1
(trans-9i): Yellowish oil. H NMR (300 MHz, CDCl3): δ = 1.31 (s,
3 H, γ-CH3), 4.05 (s, 1 H, δ-H), 7.07 (d, J = 15.4 Hz, 1 H, β-H),
2Ј-OH) ppm. 13C NMR (75 MHz, CDCl3): δ = 21.2 (γ-CH3), 62.4
(C-γ), 66.9 (C-δ), 118.5 (C-3Ј), 118.8 (C-5Ј), 119.4 (C-1Ј), 126.4 (C-
2886
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© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2007, 2877–2887

Epoxidation of Cinnamylideneacetophenones
FULL PAPER
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α), 126.5 (C-2,6), 128.1 (C-4), 128.3 (C-3,5), 129.9 (C-6Ј), 134.3 (C-
1), 136.6 (C-4Ј), 144.9 (C-β), 163.4 (C-2Ј), 193.3 (C=O) ppm. MS:
m/z (%) = 280 (7) [M]+, 264 (16), 249 (5), 238 (12), 237 (35), 224
(11), 223 (14), 219 (17), 175 (19), 174 (100), 159 (37), 145 (8), 131
(55), 121 (34), 115 (9), 105 (9), 93 (11), 91 (8), 77 (16), 65 (18), 53
(13), 51 (7). HRMS-EI: C18H16O3 [M]+ 280.1099; found 280.1106.
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Sincere thanks are expressed to the University of Aveiro, Fundação
para a Ciência e a Tecnologia, Portugal, and Fundo Europeu de
Desenvolvimento Regional (FEDER), Portugal, for funding the
Organic Chemistry Research Unit and the project POCTI/QUI/
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(PRODEP 5.3) for financial support.
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Received: February 12, 2007
Published Online: April 18, 2007
Eur. J. Org. Chem. 2007, 2877–2887
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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