A simple access to biologically important trans-stilbenes via Ru-catalyzed cross metathesis

Article abstract of DOI:10.1055/s-2005-918506

The cross metathesis of methoxy- or acetoxy-substituted styrenes using the Grubbs II catalyst affords unsymmetrical (mixed) E-stilbenes with astonishingly high selectivity (up to 79% yield). This approach offers a short and flexible synthesis of variously substituted stilbenes, which are derivatives or precursors of biologically important compounds such as resveratrol, piceatannol, and pinostilbene. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2005-918506

PAPER
273
A Simple Access to Biologically Important trans-Stilbenes via Ru-Catalyzed
Cross Metathesis
t
rans-Stilb
a
enes via Ru
n
-CatalyzedC
n
ross Metath
a
esis Velder, Stefanie Ritter, Johann Lex, Hans-Günther Schmalz*
Institute of Organic Chemistry, Universität zu Köln, Greinstrasse 4, 50939 Cologne, Germany
Fax +49(221)4703064; E-mail: schmalz@uni-koeln.de
Received 21 June 2005; revised 27 July 2005
Dedicated to Prof. Herbert Schumann on the occasion of his 70th birthday
pounds, other metal-catalyzed coupling reactions have
Abstract: The cross metathesis of methoxy- or acetoxy-substituted
styrenes using the Grubbs II catalyst affords unsymmetrical (mixed)
E-stilbenes with astonishingly high selectivity (up to 79% yield).
This approach offers a short and flexible synthesis of variously sub-
stituted stilbenes, which are derivatives or precursors of biological-
ly important compounds such as resveratrol, piceatannol, and
pinostilbene.
been evaluated as well.8
Against this background, it is surprising that olefin cross
metathesis9 has, so far, found little application in the syn-
thesis of stilbenes. Using a Mo-based catalyst, Schrock et
al. demonstrated that E-stilbene is formed from styrene in
a highly diastereoselective manner.10 Chang et al. applied
the Ru-based Grubbs II catalyst 211 to the preparation of
symmetrical stilbenes of type 4 (R = Cl, CF3, OAc, OMe)
from the corresponding para-substituted styrenes 3
(Scheme 1).12
Key words: cross metathesis, ruthenium catalysis, resveratrol, stil-
benes
In recent years, polyhydroxylated stilbenes such as resver-
atrol (1a) and piceatannol (1b) have gained tremendous
importance especially due to their potential for the pre-
vention and therapy of cancer.1 Compounds of type 1
(R = OH, OMe, or OGly) have been identified, as metab-
olites in more than 70 different plant species, as phyto-
alexin suppressants, for instance, in the growth of
pathogenic fungi.2 Moreover, these compounds exhibit a
variety of other interesting biological properties including
cardiovascular protecting effects.3 Very recently, com-
pound 1e was found to enhance the activity of antibiotics
by blocking the efflux pumps of bacterial cells.4
N
N
Mes
Cl
Cl
Mes
Ph
Ru
PCy3
R
2
R
R
3
4
Scheme 1 Synthesis of symmetrical stilbenes by cross metathesis
Attempts by Chang et al. to achieve selective cross me-
tathesis between two different styrene derivatives (with
electronically different substituents) were reported to pro-
duce inseparable product mixtures in ‘rather statistical’
ratios, and these authors thus concluded that ‘this ap-
proach is not suitable for obtaining unsymmetrical stil-
benes with practical purposes’.12
R1
R2
R3
R4
R5
1
1a: R1 = R3 = R5 = OH (Resveratrol)
1b: R1 = R3 = R4 = R5 = OH (Piceatannol)
1c: R1 = R5 = OH, R3 = OMe (Pinostilbene)
1d: R1 = R3 = OMe, R5 = OH (Pterostilbene)
1e: R1 = R3 = R5 = OMe
In the course of our own research in the field of bioactive
stilbenes13 we decided to reinvestigate the possibility of
employing cross metathesis (employing the Ru-catalyst 2)
for the synthesis of compounds of type 1 with a special fo-
cus on methoxy-substituted compounds. As a particularly
relevant case, we first studied the reaction between 4-
methoxystyrene (5) and 3,5-dimethoxystyrene (6) to give
the resveratrol derivative 1e (Scheme 2).
Figure 1
Since the first laboratory preparation of resveratrol in
19415 many oxy-functionalized stilbenes have been syn-
thesized, most commonly by exploiting Wittig-type
olefinations6 or Heck couplings of styrenes with aryl ha-
lides.7 Due to the large amount of interest in such com-
When a solution of styrenes 5 and 6 (1:1) in dichlo-
romethane was heated to 40 °C for 1.5 hours in the pres-
ence of 2 mol% of the catalyst 2, we were pleased to find
that the desired (mixed) compound 1e was formed as the
major product (Table 1, entry 3). According to GC-MS
analysis, the crude mixture of metathesis products consist-
ed of 72% of 1e along with 28% of the symmetrical stil-
bene 7 formed from two molecules of 5.
SYNTHESIS 2006, No. 2, pp 0273–0278
x
x
.
x
x
.2
0
0
5
Advanced online publication: 21.12.2005
DOI: 10.1055/s-2005-918506; Art ID: T08805SS
© Georg Thieme Verlag Stuttgart · New York

274
J. Velder et al.
PAPER
MeO
MeO
OMe
R
OMe
9 (R = Me)
10 (R = OAc)
11
1e
7
OMe
OMe
5
2 mol% 2
MeO
MeO
MeO
OMe
CH2Cl2,
40 °C, 1.5 h
chromato-
graphy
OMe
OMe
OMe
OMe
6
12
13
Figure 2 Additional styrenes used in this study.
MeO
8
OMe
olefination, we then evaluated the scope of the methodol-
ogy by trying various combinations (Table 2).
Scheme 2 Synthesis of 1e by cross metathesis
All reactions were performed on a 1 mmol scale under the
proven conditions (2 mol% of 2, CH2Cl2, 40 °C, 1.5
hours). Based on previous experience (Table 1, 1e), the
more electron-rich styrenes, e.g. the bis-methoxy com-
pounds 6 and 13, were generally used in excess (1.5
equivalents). Electronically similar styrenes were reacted
in a 1:1 ratio. The crude reaction mixture was analyzed by
GCMS to determine the product composition before the
main product was isolated by flash chromatography.
In a series of further experiments, we varied the ratio of
the starting materials in order to probe its influence on the
product distribution (Table 1). The best result was ob-
tained when 6 was used in 1.5 fold excess (Table 1, entry
4). As Table 1 also suggests, styrene 5 has a significantly
higher tendency (compared to 6) to undergo homo-me-
tathesis, i.e. to form the symmetrical stilbene 7. In con-
trast, the symmetrical product 8, resulting from
‘dimerization’ of 6, only appeared when this more elec-
tron rich styrene was used in excess. At the same time, the
formation of 7 (as the faster forming symmetrical by-
product) was suppressed in the presence of an excess of 6.
Table 2 Results of Various Cross Metathesis Reactions
Entry Styrene I
(1.5 equiv) (1.0 equiv)
Styrene II Products (% ratio)a
Yieldb
1
2
6
9
14/8/25 (80:11:9)
15/8/26 (60:39:1)
no conversion
79%
74%
Table 1 Cross Metathesis Reactions – Investigation of Product Dis-
tribution
6
10
Productsa
Entry
Equiv of Equiv of
3
6
11
12
13
5
5
6
1e (%)
7 (%)
46
8 (%)
4
6
16/8/27 (79:13:7)
17/8/28 (73:10:17)
18/28/7 (64:24:11)
19/28/25 (67:20:13)
20/28/26 (64:31:5)
no conversion
77%
62%
65%
75%
67%
1
2
3
4
5
2.0
1.5
1.0
1.0
1.0
1.0
1.0
1.0
1.5
2.0
54
47
72
88
57
–
5
6c
53
–
6
13
28
–
7
13
13
13
13
9
5
7
8
10
11
12
9
17
21
9
a Relative product ratios (peak areas) as determined by GCMS.
10
11
12
13
21/28/27 (69:17:14)
22/7/25 (81:7:11)
23/7/26 (62:20:18)
24/25/26 (77:17:5)
67%
75%
60%
65%
5c
The good selectivity observed with 1.5 equivalents of 6
(Table 1, entry 4) and the fact that products 1e, 7, and 8
are easily separable by flash chromatography indicate that
cross metathesis is indeed a very convenient route for the
synthesis of 1e (Scheme 1). Repetition of the reaction on
a preparative scale (using up to 1 g of 5) afforded the de-
sired product 1e in 76% yield after chromatographic puri-
fication.
5c
9c
10
10
a Relative product ratios (peak areas) as determined by GCMS from
the crude reaction mixture.
b Yield of main product after flash chromatography.
c In this case, only 1.0 equiv was used.
This very promising result prompted us to address the
question whether other unsymmetrical stilbenes could
eventually be synthesized in a related fashion. Using a set
of seven different styrenes (5, 6, 9, 10, 11, 12, and 13;
Figure 2), which are either commercially available or eas-
ily prepared from the corresponding aldehydes by Wittig
The structure of the various stilbenes isolated (Figure 3)
was confirmed by NMR spectroscopy and MS. In all
cases, the E-isomer was formed exclusively within the
analytical limits (NMR, GCMS, HPLC). Notably, experi-
ments employing the ortho-methoxy-substituted styrene
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trans-Stilbenes via Ru-Catalyzed Cross Metathesis
275
11 did not give any conversion, probably due to the for- The structure of compounds 8 and 28 was additionally
mation of an inactive chelate carbene complex intermedi- confirmed by X-ray crystal structure analysis (Figures 4
ate.14
and 5). Notably, the methoxy substituents are always po-
sitioned within the arene plane (sp2 hybridized).15
R
OMe
MeO
R
OMe
16 (R = H)
17 (R = OMe)
OMe
14 (R = Me)
15 (R = OAc)
OMe
OMe
OMe
MeO
Figure 5 Structure of compound 28 in the crystalline state.
R
OMe
OMe
21
It should be mentioned that the identity of all products
formed in the reactions listed in Tables 1 and 2 was se-
cured by isolation and characterization, and all signals in
the GCMS spectra (Figure 6) could be unambiguously as-
signed by using authentic samples (and by logical analysis
of reaction mixtures resulting from different pairs of sty-
rene components).
18 (R = OMe)
19 (R = Me)
20 (R = OAc)
Me
R
OAc
24
OMe
22 (R = Me)
23 (R = OAc)
R
OMe
R
MeO
R
27 (R = H)
28 (R = OMe)
R
25 (R = Me)
26 (R = OAc)
Figure 3 Various stilbenes prepared.
Figure 6 GCMS analysis of the crude product mixture obtained ac-
cording to Scheme 2 under the conditions given in Table 1, entry 4.
As the results given in Table 2 clearly demonstrate, the
desired mixed (unsymmetrical) metathesis products were
formed predominantly in all cases and could be isolated in
satisfying yields (62–79%). While the selectivity ob-
served with electronically different starting styrenes was
already surprising, the outcome of the reaction between 6
and 13 (1:1 ratio) is particularly remarkable (Table 2, en-
try 5). Despite the rather small electronic difference be-
tween the two components, i.e. 3,4-dimethoxystyrene (6)
and 3,5-dimethoxystyrene (13), the cross metathesis prod-
uct (17) formed more than 70% of the product mixture
(while the statistical expected yield would be only 50%).
In conclusion, we have shown that Ru-catalyzed cross
metathesis employing the Grubbs-II catalyst opens a very
direct synthetic access to a broad variety of unsymmetri-
cally (and symmetrically) substituted trans-stilbenes.
From an operational point of view, the protocol is partic-
ularly attractive because readily available starting materi-
als (styrenes) are reliably converted into valuable
products in a single step. At this point it may be worth
Figure 4 Structure of compound 8 (two independent molecules) in
the crystalline state.
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276
J. Velder et al.
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13C NMR (75 MHz, CDCl3): d = 55.4 (OCH3), 100.2 (C-4), 104.7
mentioning that the selective cleavage of methoxy groups
is possible as we have previously shown for the high
(C-2, C-6), 129.2 (C-7), 139.2 (C-1), 161.0 (C-3, C-5).
yielding conversion of 1e into 1c.13b Thus we are optimis- HRMS: m/z calcd for C18H20O4 (M+): 300.1361; found: 300.136.
tic that the method described in this paper will find appli-
cation in the search for new oxy-substituted stilbenes with
useful biological properties.
(E)-1-(4¢-Methylphenyl)-2-(3,5-dimethoxyphenyl)ethene (14)
Yield: 79%; mp 51 °C (lit.18 50–52 °C); tR 10.7 min.
1H NMR (300 MHz, CDCl3): d = 3.03 (s, 3 H, CH3), 3.88 (s, 6 H,
OCH3), 6.37 (t, 1 H, J = 2.1, H-4), 6.65 (d, 2 H, J = 2.1 Hz, H-2, H-
6), 6.97 (d, 1 H, J = 16.5 Hz, CH=), 7.06 (d, 1 H, J = 16.5 Hz, =CH),
7.16 (d, 2 H, J = 8.1 Hz, H-3¢, H-5¢), 7.40 (d, 2 H, J = 8.1 Hz, H-2¢,
H-6¢).
All solvents were redistilled. All reactions were carried out under an
inert atmosphere of argon. Reactions were monitored by GC-MS
using an Agilent Technologies gas chromatograph (GC 6890N)
coupled with a mass selective detector (HP 5973N) and an auto-
sampler (HP 7683). Samples were separated on a 30 m × 0.25 mm
HP-5 MS column. The column temperature was initially held at
50 °C for 2 min, then the temperature was increased to 300 °C at a
rate of 25 °C per min and held at 300 °C for 5 min. The total run
time was 17 min. Injector temperature was maintained at 300 °C,
and the injection volume was 1.0 mL in the split mode. MS were
scanned in the m/z range 35–500 by EI at 70 eV. Flash column chro-
matography was performed on silica gel (particle size 40–63 mm,
Merck). The handling of air-sensitive materials was performed in a
glove-box (Labmaster 130, mBraun) under argon. NMR spectra
were acquired on a Bruker DPX 300 spectrometer operating at 300
MHz for 1H NMR and 75 MHz for 13C NMR.
13C NMR (75 MHz, CDCl3): d = 21.2 (CH3), 55.2 (OCH3), 99.8 (C-
4), 104.4 (C-2, C-6), 126.5 (C-3¢, C-5¢), 127.6 (C=), 129.1 (=C),
129.4 (C-2¢, C-6¢), 134.3 (C¢), 137.6 (C-1), 139.5 (C-4¢), 160.9 (C-
3, C-5).
HRMS: m/z calcd for C17H18O2 (M+): 254.1307; found: 254.131.
(E)-1-(4¢-Acethoxyphenyl)-2-(3,5-dimethoxyphenyl)ethene (15)
Yield: 74%; mp 127 °C (lit.19 128 °C); tR 11.8 min.
1H NMR (300 MHz, CDCl3): d = 2.29 (s, 3 H, CH3), 3.82 (s, 6 H,
OCH3), 6.38 (t, 1 H, J = 2.1 Hz, H-4), 6.64 (d, 2 H, J = 2.1 Hz, H-
2, H-6), 6.96 (d, 1 H, J = 16.2 Hz, CH=), 7.04 (d, 1 H, J = 16.2
Hz,=CH), 7.07 (d, 2 H, J = 7.0 Hz, H-3¢, H-5¢), 7.49 (d, 2 H, J = 7.0
Hz, H-2¢, H-6¢).
13C NMR (75 MHz, CDCl3): d = 23.2 (CH3), 55.2 (OCH3), 100.1
(C-4), 104.6 (C-2, C-6), 121.8 (C-3¢, C-5¢), 127.4 (C-2¢, C-6¢), 127.5
(CH=), 128.2 (=CH), 135.1 (C-1¢), 139.2 (C-1), 161.0 (C-3, C-5),
169.5 (C=O).
1e; Typical Procedure
The catalyst (Grubbs-II, 2 mol%) was weighed into a 25 mL
Schlenk tube, in a glove-box, which was then sealed with a rubber
septum. This was then taken out of the box, connected to an argon
vacuum double manifold and equipped with a reflux condenser un-
der argon. A solution of styrenes 5 (1 mmol) and 6 (1.5 mmol) in
CH2Cl2 (10 mL, 0.1 M) was then added via syringe and the resulting
solution was refluxed for 1.5 h under argon. At this point, a sample
was taken for GCMS analysis (via syringe). After allowing the re-
action mixture to cool to r.t., the solvent was evaporated in vacuo
and the crude product was purified by flash chromatography (cyclo-
hexane–EtOAc, 10:1) to give 205 mg (0.76 mol; 76%) of the cross
metathesis product (E)-1-(4¢-methoxyphenyl)-2-(3,5-dimethoxy-
phenyl)ethene (1e) as a white solid.
HRMS: m/z calcd for C18H18O3 (M+): 298.1205; found: 298.120.
(E)-1-(3¢-Methoxyphenyl)-2-(3,5-dimethoxyphenyl)ethene (16)
Yield: 77%; oil; tR 11.3 min.
1H NMR (300 MHz, CDCl3): d = 3.82 (s, 6 H, OCH3), 3.84 (s, 3 H,
OCH3), 6.34 (t, 1 H, J = 2.1 Hz, H-4), 6.61 (d, 2 H, J = 2.1 Hz, H-
2, H-6), 6.77 (dd, 1 H, J = 8.1, 1.5 Hz, H-4¢), 6.98–7.03 (m, 3 H, H-
2¢, H-7, H-8), 7.24 (dd, 1 H, J = 8.1, 7.5 Hz, H-5¢), 7.04 (d, 1 H,
J = 7.5 Hz, H-6¢).
13C NMR (75 MHz, CDCl3): d = 55.2 (OCH3), 55.3 (2 × OCH3),
100.0 (C-4), 104.6 (C-2, C-6), 111.8 (C-2¢), 113.4 (C-4¢), 119.3 (C-
6¢), 128.9 (C-7), 129.0 (C-8), 129.1 (C-5¢), 138.6 (C-1), 139.2 (C-
1¢), 159.9 (C-3¢), 161.0 (C-3, C-5).
Mp 55 °C (lit.15a 55–57 °C); tR 11.4 min.
1H NMR (300 MHz, CDCl3): d = 3.81 (s, 6 H, OCH3), 3.82 (s, 3 H,
OCH3), 6.38 (t, 1 H, J = 2.4 Hz, H-4), 6.65 (d, 2 H, J = 2.4 Hz, H-
2, H-6), 6.89 (d, 2 H, J = 8.7 Hz, H-3¢, H-5¢), 6.90 (d, 1 H, J = 16.2
Hz, HC=), 7.05 (d, 1 H, J = 16.2 Hz, =CH), 7.44 (d, 2 H, J = 8.7 Hz,
H-2¢, H-6¢).
HRMS: m/z calcd for C17H18O3 (M+): 270.1256; found: 270.126.
13C NMR (75 MHz, CDCl3): d = 55.4 (OCH3), 99.7 (C-4), 104.4 (C-
2, C-6), 114.2 (C-3¢, C-5¢), 126.6 (C=), 127.8 (C-2¢, C-6¢), 128.8
(=C), 130.0 (C-1), 139.7 (C-1¢), 159.4 (C-4¢), 161.0 (C-3, C-5).
(E)-1-(3¢,5¢-Dimethoxyphenyl)-2-(3,4-dimethoxyphenyl)ethene
(17)
Yield: 62%; mp 182 °C (lit.20 182–183 °C); tR 12.0 min.
HRMS: m/z calcd for C17H18O3 (M+): 270.1256; found: 270.126.
1H NMR (300 MHz, CDCl3): d = 3.81 (s, 6 H, OCH3), 3.88 (s, 3 H,
OCH3), 3.92 (s, 3 H, OCH3), 6.37 (t, 1 H, J = 2.2 Hz, H-4¢), 6.64 (d,
2 H, J = 2.2 Hz, H-2¢, H-6¢), 6.83 (d, 1 H, J = 7.5 Hz, H-5), 6.88 (d,
1 H, J = 16.0 Hz, H-7), 7.01 (d, 1 H, J = 16.0 Hz, H-8), 7.02 (dd, 1
H, J = 7.5, 1.8 Hz, H-6), 7.04 (d, 1 H, J = 1.8 Hz, H-2).
13C NMR (75 MHz, CDCl3): d = 55.3 (OCH3), 55.8 (OCH3), 55.9
(OCH3), 99.7 (C-4¢), 104.3 (C-2¢, C-6¢), 108.8 (C-2), 111.2 (C-5),
120.0 (C-6), 126.7 (C-7), 128.9 (C-8), 130.9 (C-1), 139.5 (C-1¢),
149.0 (C-3), 149.1 (C-4), 160.9 (C-3¢, C-5¢).
(E)-1,2-(4,4¢-Methoxyphenyl)ethene (7)
Mp 214 °C (lit.16 216 °C); tR 10.6 min.
1H NMR (300 MHz, CDCl3): d = 3.83 (s, 3 H, OCH3), 6.89 (d, 2 H,
J = 8.7 Hz, H-2, H-6), 6.93 (s, 1 H, H-7), 7.43 (d, 2 H, J = 8.7 Hz,
H-3, H-5).
13C NMR (75 MHz, CDCl3): d = 55.3 (OCH3), 114.2 (C-3, C-5),
126.2 (C-7), 127.4 (C-2, C-6), 130.5 (C-1), 159.0 (C-4).
HRMS: m/z calcd for C18H20O4 (M+): 300.1361; found: 300.136.
HRMS: m/z calcd for C16H16O2 (M+): 240.1105; found: 240.115.
(E)-1-(4¢-Methoxyphenyl)-2-(3,4-dimethoxyphenyl)ethene (18)
Yield: 65%; mp 138 °C (lit.21 135 °C); tR 11.4 min.
(E)-1,2-(3,3¢,5,5¢-Dimethoxyphenyl)ethene (8)
Mp 142 °C (lit.17 141–144 °C); tR 12.1 min.
1H NMR (300 MHz, CDCl3): d = 3.81 (s, 3 H, 4¢-COCH3), 3.88 (s,
3 H, 3-COCH3), 3.93 (s, 3 H, 4-COCH3), 6.83 (d, 1 H, J = 8.4 Hz,
H-5), 6.88 (d, 2 H, J = 8.7 Hz, H-3¢, H-5¢), 6.91 (s, 2 H, H-7, H-8),
1H NMR (300 MHz, CDCl3): d = 3.81 (s, 6 H, OCH3), 6.4 (t, 1 H,
J = 2.1 Hz, H-4), 6.67 (d, 2 H, J = 2.1 Hz, H-2, H-6), 7.00 (s, 1 H,
H-7).
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trans-Stilbenes via Ru-Catalyzed Cross Metathesis
277
7.00 (dd, 1 H, J = 8.4, 2.1 Hz, H-6), 7.04 (d, 1 H, J = 2.1 Hz, H-2),
7.42 (d, 2 H, J = 8.7 Hz, H-2¢, H-6¢).
13C NMR (75 MHz, CDCl3): d = 55.3 (OCH3), 55.8 (OCH3), 55.9
(OCH3), 108.6 (C-2), 111.2 (C-5), 114.1 (C-3¢, C-5¢), 119.5 (C-6),
126.4 (C-7, C-8), 127.4 (C-2¢, C-6¢), 130.3 (C-1¢), 130.8 (C-1),
148.6 (C-4), 149.1 (C-3), 159.0 (C-4¢).
1H NMR (300 MHz, CDCl3): d = 2.29 (s, 3 H, CH3), 3.81 (s, 3 H,
OCH3), 6.88 (d, 2 H, J = 8.8 Hz, H-3¢, H-5¢), 6.93 (d, 1 H, J = 16.0
Hz, H-7), 7.00 (d, 1 H, J = 16.0 Hz, H-8), 7.06 (d, 2 H, J = 8.7 Hz,
H-3, H-5), 7.43 (d, 2 H, J = 8.8 Hz, H-2¢, H-6¢), 7.47 (d, 2 H, J = 8.7
Hz, H-2, H-6).
13C NMR (75 MHz, CDCl3): d = 21.1 (CH3), 55.28 (OCH3), 114.1
(C-3¢, C-5¢), 121.7 (C-3, C-5), 125.5 (C-7), 127.1 (C-2, C-6), 128.4
(C-2¢, C-6¢), 128.4 (C-8), 129.9 (C-1), 135.5 (C-1¢), 149.7 (C-4),
159.3 (C-4¢), 169.4 (C=O).
HRMS: m/z calcd for C17H18O3 (M+): 270.1256; found: 270.126.
(E)-1-(4¢-Methylphenyl)-2-(3,4-dimethoxyphenyl)ethene (19)
Yield: 75%; mp 168 °C (lit.22 169 °C); tR 10.8 min.
HRMS: m/z calcd for C17H16O3 (M+): 268.1099; found: 268.110.
1H NMR (300 MHz, CDCl3): d = 2.35 (s, 3 H, CH3), 3.88 (s, 3 H,
OCH3), 3.94 (s, 3 H, OCH3), 6.84 (d, 1 H, J = 8.4 Hz, H-5), 6.94 (d,
1 H, J = 16.2 Hz, H-7), 7.01 (d, 1 H, J = 16.2 Hz, H-8), 7.03 (dd, 1
H, J = 8.4, 1.8 Hz, H-6), 7.06 (d, 1 H, J = 1.8 Hz, H-2), 7.15 (d, 2
H, J = 8.1 Hz, H-3¢, H-5¢), 7.40 (d, 2 H, J = 8.1 Hz, H-2¢, H-6¢).
13C NMR (75 MHz, CDCl3): d = 21.3 (CH3), 55.9 (OCH3), 56.0
(OCH3), 108.7 (C-2), 111.3 (C-5), 119.8 (C-6), 126.2 (C-2¢, C-6¢),
126.8 (C-6), 127.5 (C-7), 129.4 (C-3¢, C-5¢), 130.7 (C-1), 134.8 (C-
1¢), 137.2 (C-4¢), 148.8 (C-4), 149.2 (C-3).
(E)-1-(4¢-Methylphenyl)-2-(4-acethoxyphenyl)ethene (24)
Yield: 65%; mp 144 °C; tR 10.5 min.
1H NMR (300 MHz, CDCl3): d = 2.29 (s, 3 H, CH3), 3.37 (s, 3 H,
O=CCH3), 7.02 (s, 2 H, CH=CH), 7.07 (d, 2 H, J = 8.4 Hz, H-3, H-
5), 7.16 (d, 2 H, J = 7.8 Hz, H-3¢, H-5¢), 7.39 (d, 2 H, J = 7.8 Hz, H-
2¢, H-6¢), 7.49 (d, 2 H, J = 8.4 Hz, H-2, H-6).
13C NMR (75 MHz, CDCl3): d = 21.2 (CH3), 21.2 (CH3), 121.7 (C-
3, C-5), 126.4 (C-2¢, C-6¢), 126.6 (C-7), 127.2 (C-2, C-6), 128.8 (C-
8), 134.3 (C-1¢), 135.3 (C-1), 137.6 (C-4¢), 149.8 (C-4), 169.4
(C=O).
HRMS: m/z calcd for C17H18O2 (M+): 254.1307; found: 254.131.
(E)-1-(4¢-Acethoxyphenyl)-2-(3,4-dimethoxyphenyl)ethene (20)
Yield: 67%; mp 113 °C; tR 11.8 min.
HRMS: m/z calcd for C17H16O2 (M+): 252.1201; found: 252.120.
(E)-1,2-(4,4¢-Methylphenyl)ethene (25)26
Mp 182 °C (lit.27 182 °C); tR 9.4 min.
1H NMR (300 MHz, CDCl3): d = 3.28 (s, 3 H, CH3), 3.88 (s, 3 H, 4-
COCH3), 3.93 (s, 3 H, 3-COCH3), 6.83 (d, 1 H, J = 8.1 Hz, H-5),
6.91 (d, 1 H, J = 16.2 Hz, CH=), 6.99 (d, 1 H, J = 16.2 Hz, =CH),
7.02 (dd, 1 H, J = 8.1, 2.1 Hz, H-6), 7.04 (d, 1 H, J = 2.1 Hz, H-2),
7.05 (d, 2 H, J = 8.7 Hz, H-3¢, H-5¢), 7.47 (d, 2 H, J = 8.7 Hz, H-2¢,
H-6¢).
13C NMR (75 MHz, CDCl3): d = 21.0 (CH3), 55.8 (OCH3), 55.8
(OCH3), 111.1 (C-5), 119.8 (C-6), 121.1 (C-3¢, C-5¢), 125.7 (C-8),
127.1 (C-2¢, C-6¢), 128.6 (C-7),130.2 (C-1), 135.3 (C-1¢), 149.0 (C-
4), 149.0 (C-3), 149.6 (C-4¢), 169.4 (C=O).
(E)-1,2-(4,4¢-Acethoxyphenyl)ethene (26)
Mp 214 °C (lit.28 215–218 °C); tR 11.7 min.
1H NMR (300 MHz, CDCl3): d = 2.29 (s, 3 H, CH3), 7.04 (s, 1 H,
CH=), 7.08 (d, 2 H, J = 8.7 Hz, H-3, H-5), 7.49 (d, 2 H, J = 8.7 Hz,
H-2, H-6).
13C NMR (300 MHz, CDCl3): d = 21.2 (CH3), 121.8 (C-3, C-5),
127.4 (C-2, C-6), 127.9 (C-7), 135.0 (C-1), 150.1 (C-4), 169.5
(C=O).
HRMS: m/z calcd for C18H18O4 (M+): 298.1205; found: 298.120.
HRMS: m/z calcd for C18H16O4 (M+): 296.1048; found: 296.105.
(E)-1-(3¢-Methoxyphenyl)-2-(3,4-dimethoxyphenyl)ethene (21)
Yield: 67%; mp 145 °C (lit.23 145–146 °C); tR 11.2 min.
(E)-1,2-(3,3¢-methoxyphenyl)ethene (27)29
Mp 201 °C; tR 10.5 min.
1H NMR (300 MHz, CDCl3): d = 3.82 (s, 3 H, 3¢-COCH3), 3.87 (s,
3 H, 3-COCH3), 3.92 (s, 3 H, 4-COCH3), 6.79 (dd, 1 H, J = 8.1, 1.5
Hz, H-4¢), 6.84 (d, 1 H, J = 8.1 Hz, H-5), 6.92 (d, 1 H, J = 16.2 Hz,
H-7), 7.01–7.08 (m, 5 H, H-2, H-2¢, H-6, H-6¢, H-8), 7.24 (dd, 1 H,
J = 8.1, 7.8 Hz, H-5¢).
13C NMR (75 MHz, CDCl3): d = 55.3 (OCH3), 55.8 (OCH3), 55.9
(OCH3), 108.7 (C-2¢), 111.2 (C-2), 111.5 (C-4¢), 112.9 (C-5), 119.0
(C-6¢), 120.0 (C-6), 126.6 (C-7), 128.7 (C-8), 129.6 (C-5¢), 130.3
(C-1), 138.9 (C-1¢), 148.9 (C-4), 149.1 (C-3), 159.8 (C-3¢).
(E)-1,2-(3,3¢,4,4¢-Dimethoxyphenyl)ethene (28)
Mp 154 °C (lit.30 155 °C); tR 11.9 min.
1H NMR (300 MHz, CDCl3): d = 3.88 (s, 3 H, OCH3), 3.93 (s, 3 H,
OCH3), 6.83 (d, 1 H, J = 8.1 Hz, H-5), 6.90 (s, 1 H, H-7), 7.02 (dd,
1 H, J = 8.1, 1.8 Hz, H-6), 7.04 (d, 1 H, J = 1.8 Hz, H-2).
13C NMR (75 MHz, CDCl3): d = 55.8 (OCH3), 55.9 (OCH3), 108.6
(C-2), 111.2 (C-5), 119.5 (C-6), 126.6 (C-7), 130.6 (C-1), 149.1 (C-
4), 148.7 (C-3).
HRMS: m/z calcd for C17H18O3 (M+): 270.1256; found: 270.126.
HRMS: m/z calcd for C18H20O4 (M+): 300.1361; found: 300.136.
(E)-1-(4¢-Methylphenyl)-2-(4-methoxyphenyl)ethene (22)
Yield: 75%; mp 123 °C (lit.24 123–124 °C); tR 10.0 min.
1H NMR (300 MHz, CDCl3): d = 2.37 (s, 3 H, CH3), 3.82 (s, 3 H,
OCH3), 6.88 (d, 2 H, J = 8.7 Hz, H-3, H-5), 6.96 (d, 1 H, J = 12.0,
CH=), 7.01 (d, 1 H, J = 12.0 Hz, =CH), 7.15 (d, 2 H, J = 8.1 Hz, H-
3¢, H-5¢), 7.37–7.45 (m, 4 H, H-2, H-2¢, H-6, H-6¢).
Acknowledgement
This work was supported by INTAS. The authors would like to
thank Andreas Adler for technical support concerning GC-MS and
HPLC analyses.
13C NMR (75 MHz, CDCl3): d = 21.2 (CH3), 55.3 (OCH3), 114.1
(C-3, C-5), 119.1 (C-2, C-6), 126.5 (C-8), 127.0 (C-2¢, C-6¢), 127.2
(C-7), 129.3 (C-3¢, C-5¢), 130.3 (C-1¢), 134.2 (C-1), 137.1 (C-4¢),
159.1 (C-4).
Note added in proof
After acceptance of this paper for publication, a related study has
been disclosed: Ferré-Filmon, K.; Delaude, L.; Demonceau, A.; No-
els, A. F. Eur. J. Org. Chem. 2005, 3319–3325.
HRMS: m/z calcd for C16H16O (M+): 224.1201; found: 224.120.
(E)-1-(4¢-Methoxyphenyl)-2-(4-acethoxyphenyl)ethene (23)
Yield: 60%; mp 167 °C (lit.25 167–168 °C); tR 11.1 min.
Synthesis 2006, No. 2, 273–278 © Thieme Stuttgart · New York

278
J. Velder et al.
PAPER
(14 h), and the additional step(s) associated with the
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Synthesis 2006, No. 2, 273–278 © Thieme Stuttgart · New York