Stereoselective synthesis of (E)-hydroxystilbenoids by ruthenium-catalyzed cross-metathesis

Article abstract of DOI:10.1002/ejoc.200500068

An efficient and highly stereoselective synthetic procedure is reported for the construction of symmetrical and unsymmetrical (E)-polymethoxystilbene and (E)-polyhydroxystilbene derivatives. The strategy rests on a cross-metathesis reaction catalyzed by stable, well-defined (alkylidene)ruthenium complexes, in particular the second-generation Grubbs catalyst [RuCl₂(=CHPh)(SIMes) (PCy₃)] [SIMes = 1,3-bis(2,4,6-trimethylphenyl)imidazolidin-2- ylidene]. The metathesis of unprotected phenolic styrenes is illustrated by the synthesis of the important phytoalexins (E)-3,4′,5-trihydroxystilbene (resveratrol) and (E)-3,3′,4,5′-tetrahydroxystilbene (piceatannol). Wiley-VCH Verlag GmbH & Co. KGaA, 2005.

Full text of DOI:10.1002/ejoc.200500068

FULL PAPER
Stereoselective Synthesis of (E)-Hydroxystilbenoids by Ruthenium-Catalyzed
Cross-Metathesis
Karine Ferré-Filmon,[a][‡] Lionel Delaude,[a] Albert Demonceau,[a] and Alfred F. Noels*[a]
Keywords: Alkenes / Homogeneous catalysis / Natural products / Resveratrol / Ruthenium
An efficient and highly stereoselective synthetic procedure
is reported for the construction of symmetrical and unsym-
metrical (E)-polymethoxystilbene and (E)-polyhydroxystil-
bene derivatives. The strategy rests on a cross-metathesis re-
action catalyzed by stable, well-defined (alkylidene)ruthe-
nium complexes, in particular the second-generation Grubbs
bis(2,4,6-trimethylphenyl)imidazolidin-2-ylidene]. The me-
tathesis of unprotected phenolic styrenes is illustrated by the
synthesis of the important phytoalexins (E)-3,4Ј,5-trihydroxy-
stilbene (resveratrol) and (E)-3,3Ј,4,5Ј-tetrahydroxystilbene
(piceatannol).
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2005)
catalyst [RuCl2(=CHPh)(SIMes)(PCy3)] [SIMes
=
1,3-
Introduction
Naturally occurring stilbenoid compounds usually dis-
play significant biological activities. Among them, resvera-
trol (3,4Ј,5-trihydroxystilbene) and its derivatives have re-
cently attracted a great deal of attention because of their
physiological properties and potential therapeutic values.[1]
Resveratrol is part of a class of molecules called phytoalex-
ins, which are defense compounds produced by higher
plants in response to pathogens and stresses (Figure 1).
Phytoalexins are present, inter alia, in grape skins and in
peanuts, but only in minute amounts that vary widely with
the growth conditions. For these reasons, they cannot be
obtained in large quantities by extractive procedures.
Hence, the search for reliable and efficient chemical synthe-
ses of resveratrol and related stilbene derivatives has
sparked an ongoing research effort in the organic chemistry
community.
Figure 1. Structures of selected phytoalexins.
From a historical point of view, Wittig or Horner–Wads-
worth–Emmons reactions were the initial methods of choice
for assembling a stilbenoid unit from two appropriately
functionalized aromatic building blocks.[2] However, these
reactions are not catalytic and usually afford poor control
over the configuration of the newly formed C=C double
bonds, thereby yielding mixtures of (E)- and (Z)-alkenes.
Owing to the development of transition-metal-assisted or-
ganic synthesis, several catalytic approaches have been pro-
posed to achieve better selectivities in the preparation of
stilbene derivatives.[3] Most strategies developed so far in-
volve palladium-mediated coupling reactions. Among them,
methods based on the Heck[4,5] and Suzuki[6] reactions
stand out for their synthetic versatility and efficiency. Other
transition-metal-promoted stilbene syntheses rely on the
McMurry coupling of aldehydes and ketones upon treat-
ment with low-valent titanium species[7,8] or on olefin me-
tathesis.[9,10] Thanks to the development of well-defined (al-
kylidene)metal complexes based on ruthenium (see struc-
tures 1–4 in Figure 2), this latter reaction has emerged as a
powerful tool for exchanging substituents across carbon–
carbon double bonds in the presence of many other func-
tional groups.[11]
Alkene cross-metathesis (CM) can, indeed, provide a
convenient access to stilbenoid compounds (Scheme 1). The
reaction has attracted much attention recently,[12] although
it has not yet attained the same level of synthetic usefulness
as ring-closing metathesis (RCM) or ring-opening metathe-
[a] Center for Education and Research on Macromolecules
(CERM), Institut de Chimie (B6a), Université de Liège,
Sart-Tilman par 4000 Liège, Belgium
Fax: +32-4-3663497
E-mail: af.noels@ulg.ac.be
[‡] Present address: DRECAM-SPCSI,
Bâtiment 462, CEA-Saclay, 91191 Gif sur Yvette, France
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DOI: 10.1002/ejoc.200500068
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K. Ferré-Filmon, L. Delaude, A. Demonceau, A. F. Noels
FULL PAPER
of unprotected phenolic styrenes into the important phyto-
alexin resveratrol.
Results and Discussion
To begin our investigations, we first examined the homo-
coupling of styrene and 4-methoxystyrene catalyzed by
complexes 1[14] and 2.[15] With the second-generation
Grubbs catalyst 1 (5 mol-%), the reactions in toluene at
110 °C were quantitative after 15 min and afforded 99.8%
of (E)-stilbene and 98.9% of (E)-4,4Ј-dimethoxystilbene,
respectively. The kinetics were slower with the first-genera-
tion Grubbs catalyst 2, leading to partial conversions, i.e.,
about 85% for both substrates, after 72 h under the same
experimental conditions. These results are in line with the
olefin categorization recently proposed by Grubbs et al. for
predicting reactivity in CM.[13] Indeed, styrenes bearing no
large ortho substituents are classified as olefins of type I
(rapid homodimerization, secondary metathesis on homo-
dimers) with catalyst 1, and as olefins of type II (slow
homodimerization, homodimers sparingly consumable)
with complex 2.
Figure 2. Structures of the ruthenium catalysts used in this study.
sis polymerization (ROMP). This is largely due to inherent
difficulties in controlling selectivities toward cross-coupling
instead of homodimerization in a process that is not favored
either by a strong enthalpic driving force (like ROMP) or
by entropic factors (like RCM).[13] Thus, to the best of our
knowledge, reports of stilbene formation by cross-metathe-
sis are still scarce in the literature.[9,10]
It is noteworthy that catalyst 1 does not promote the me-
tathesis of 2-methoxystyrene under the same experimental
conditions. This may be due to the formation of a less active
carbene species possessing a chelated methoxy ligand. To
probe the validity of this hypothesis, we prepared the che-
lated methoxy complex [(PCy3)Cl2Ru{=CH(C6H4-o-OMe)}]
(4), which has previously been described by Hoveyda and
co-workers,[16] and assessed its catalytic efficiency toward
styrene CM. It was found to be a very poor catalyst, since
only 10% of styrene was consumed after 24 h in refluxing
Scheme 1. Olefin cross-metathesis reaction.
The coupling of terminal alkenes into symmetrical in- toluene.
ternal olefins has been investigated by Schrock and co-
Next, the cross-metathesis of 4-methoxystyrene and 3,5-
workers using a range of (alkylidene)(imido)molybde- dimethoxystyrene was investigated using a 1:1 mixture of
num(vi) complexes as catalysts.[9] Only (E)-stilbene was ob- the two olefins in the presence of catalyst 1 (Scheme 2). As
tained when styrene was used as substrate, but the yields expected, the time required to reach completion was shorter
remained low except when [Mo(CHCMe2Ph)(N-2,6- when the reaction was carried out in refluxing toluene than
Me2C6H3){OCMe2(CF3)}2] was employed as catalyst under in refluxing dichloromethane. In both solvents, however, the
carefully adjusted conditions.
reaction mixtures had the same final composition. With a
In 2002, Chang et al. reported that the cross-metathesis 5 mol-% catalyst loading, complete conversion occurred
of a polymer-grafted styrenyl ether with substituted sty- within 1 h in refluxing toluene and the three coupling prod-
renes affords stilbenoid derivatives in good yields and with ucts were obtained in a close to statistical distribution, i.e.,
complete (E)-selectivity using complex 1 as catalyst.[10] The about 50% of the cross-product (E)-3,4Ј,5-trimethoxystil-
advantages of this solid-phase metathesis approach lie in bene (6) and 25% each of homoproducts 5 and 7 (Table 1).
the expected inhibition of the supported substrate self- In refluxing dichloromethane under the same conditions,
coupling, as well as the ease of product separation from the 24 h were needed to fully consume the starting materials.
reaction mixture. However, the reaction rates are signifi- When the proportion of complex 1 was reduced to 1 mol-
cantly lower than under homogeneous conditions, despite %, conversion levelled off at 85% after 2 h in refluxing tolu-
the fact that 20 mol-% of the expensive catalyst 1 was used. ene and did not further increase when the reaction time was
We have recently launched a study of the formation of extended to 24 h. Rather similar kinetics and proportions
stilbenoid derivatives by ruthenium-catalyzed cross-metath- of products 5–7 were obtained when the Hoveyda–Grubbs
esis of styrene derivatives. Herein, we disclose our results catalyst 3[17] (5 mol-%) was substituted for its parent 1
demonstrating the ability of ruthenium complexes 1–3 to (Table 1). Complex 2, on the other hand, did not lead to
act as catalysts for the preparation of polyhydroxy- and po- any reaction in dichloromethane, even at reflux. In toluene,
lymethoxystilbenes by CM. The underlying objective that it eventually promoted CM between 4-methoxystyrene and
guided us in this research was to achieve the mixed coupling 3,5-dimethoxystyrene, but full conversion of the substrates
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Stereoselective Synthesis of (E)-Hydroxystilbenoids
FULL PAPER
could not be achieved, even when the reaction time and the reagent[19] cleanly afforded pure resveratrol in 80% overall
proportion of catalyst were increased. Therefore, we de- yield.
cided to carry out all further experiments with 3–5 mol-%
of complex 1 in refluxing toluene (or THF, vide infra).
A more direct access to resveratrol, and to polyhy-
droxystilbene derivatives in general, would be available if
cross-metathesis could be accomplished without protection/
deprotection of the styrenyl substrate hydroxy groups. This
would constitute a significant advance since, to the best of
our knowledge, all the synthetic routes devised so far in-
volve a preliminary etherification and a subsequent cleavage
step.[3] A quick survey of the literature revealed that the
second-generation Grubbs catalyst might be suitable for the
task. Indeed, compared to its predecessor 2, complex 1 tol-
erates a wider range of functional groups, including amines,
sulfides, and phenols.[20] It has been successfully used for
the preparation of oxazolylphenol ligands by CM,[20] for
the cross-coupling of eugenol with (Z)-1,4-butenediol,[21]
and for the total synthesis of resorcylic macrocycles by
RCM.[22] We therefore investigated the reactions of several
(poly)hydroxystyrenes in the presence of this (carbene)ru-
thenium complex. The homocouplings of 4-hydroxystyrene,
3,5-dihydroxystyrene, and 3,4-dihydroxystyrene were first
examined using 3–5 mol-% of catalyst 1 (Scheme 3). To our
great satisfaction, the reactions proceeded very cleanly, and
Scheme 2. Cross-metathesis of 4-methoxystyrene and 3,5-dimeth-
oxystyrene catalyzed by ruthenium complexes 1–3.
Table 1. Cross-metathesis of 4-methoxystyrene and 3,5-dimeth- quantitative conversions were achieved within 1 h in re-
oxystyrene catalyzed by ruthenium complexes 1–3 (5 mol-%) in re-
fluxing toluene for 1 h.
fluxing THF. Recourse to this solvent as the reaction me-
dium was dictated by the poor solubility of the polar phe-
Catalyst
Isolated yield [%]
Product distribution 5/6/7 [%]
nolic substrates in toluene. After purification by flash
chromatography, (E)-hydroxystilbenes 8–10 were isolated in
high yields (Table 2).
1
2
3
83
78[a]
81
19:63:18
22:62:16
20:52:28
[a] GC yield after 2 h of reaction.
Although ruthenium complexes 1–3 afford only (E)-
double bonds, they obviously lack selectivity by giving a
close to statistical mixture of three different coupling prod-
ucts. This is probably due to their ability to perform second-
ary metathesis on the newly formed C=C double bond of
the stilbenoid compounds.[13] In order to confirm this hy-
pothesis, pure trimethoxylated compound 6 was mixed with
5 mol-% of complex 1. After about 1 h in refluxing toluene,
Scheme 3. Homocoupling of various (poly)hydroxystyrene deriva-
tives catalyzed by ruthenium complex 1.
Additionally, the ruthenium-catalyzed homocouplings of
the reaction mixture contained the three substituted (E)- 4-hydroxy-3-methoxystyrene and of 3,4-bis(trimethylsily-
stilbenes 5–7 in an 18:55:27 ratio. Additional unidentified loxy)styrene were carried out in refluxing toluene with
products were also detected by gas chromatography and ac- 5 mol-% of complex 1. The consumption of both alkoxy
counted for 9% of the mass balance.
and silyloxy derivatives was total after 30–60 min and led to
A way to improve the selectivity for the unsymmetrical (E)-4,4Ј-dihydroxy-3,3Ј-dimethoxystilbene (11) and to (E)-
cross-product is to introduce one substrate in excess. Thus, 3,3Ј,4,4Ј-tetrakis(trimethylsilyloxy)stilbene (12), respec-
when the coupling of 3,5-dimethoxystyrene with 10 equiv. tively, in close to quantitative yields (Table 2).
of commercially available 4-methoxystyrene was performed
In another experiment designed to obtain stilbene deriva-
in toluene at 110 °C using 5 mol-% of complex 1, cross- tives bearing both hydroxy and methoxy functional groups,
product 6 was isolated in 94% yield. The workup was par- the ruthenium-catalyzed heterocoupling of 4-hydroxysty-
ticularly easy to carry out, since the (E)-4,4Ј-dimethoxystil- rene and 4-methoxystyrene was carried out in refluxing tol-
bene (5) present as a side-product precipitated from the re- uene. The two coupling partners were introduced in 1:1
action mixture upon cooling to room temperature. Pro- stoichiometric proportions together with 5 mol-% of com-
tected resveratrol 6 could therefore be obtained by a simple plex 1. The consumption of both substituted styrenes was
filtration followed by flash-chromatographic purification. total after 30 min and led to a mixture of the three products
Demethylation of (E)-3,4Ј,5-trimethoxystilbene by treat- 5, 13, and 8 in 13:65:22 molar proportions (Scheme 4).
ment with boron tribromide[18] or with the recently de- These products were easily separated by column
scribed boron trichloride/tetra-n-butylammonium iodide chromatography. Thus, a recycling process involving ruthe-
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K. Ferré-Filmon, L. Delaude, A. Demonceau, A. F. Noels
Table 2. Homocoupling of various (poly)hydroxystyrene derivatives catalyzed by ruthenium complex 1.
FULL PAPER
Substrate
Product
Isolated yield [%]
4-Hydroxystyrene
3,5-Dihydroxystyrene
3,4-Dihydroxystyrene
4-Hydroxy-3-methoxystyrene
3,4-Bis(trimethylsilyloxy)styrene
(E)-4,4Ј-dihydroxystilbene (8)
70[a]
89[b]
92[b]
89[c]
97[c]
(E)-3,3Ј,5,5Ј-tetrahydroxystilbene (9)
(E)-3,3Ј,4,4Ј-tetrahydroxystilbene (10)
(E)-4,4Ј-dihydroxy-3,3Ј-dimethoxystilbene (11)
(E)-3,3Ј,4,4Ј-tetrakis(trimethylsilyloxy)stilbene (12)
[a] 1 h reaction in refluxing THF using 5 mol-% of Ru catalyst 1. [b] 1 h reaction in refluxing THF using 3 mol-% of Ru catalyst 1. [c]
1 h reaction in refluxing toluene using 5 mol-% of Ru catalyst 1.
nium-catalyzed cleavage of the homodimers 5 and 8 with
ethylene or their direct re-equilibration into cross-product
13 is conceivable. We examined these two options using stil-
bene 5 as a model substrate, since it is the main by-product
formed when an excess of 4-methoxystyrene was used in
cross-coupling experiments (vide supra).
Scheme 5. Ethenolysis of (E)-stilbene and (E)-4,4Ј-dimethoxystil-
bene (5) catalyzed by ruthenium complex 1.
Finally, since all the indicators were favorable, we exam-
ined the direct synthesis of two important phytoalexins
starting from unprotected phenolic styrenes (Scheme 6).
The cross-metathesis of 1 equiv. of p-hydroxystyrene and
1 equiv. of 3,5-dihydroxystyrene in THF led to the forma-
tion of resveratrol (14) in a close to statistical equilibrium
Scheme 4. Cross-metathesis of 4-hydroxystyrene and 4-methoxysty-
rene catalyzed by ruthenium complex 1.
with the two homocoupling products 8 and 9 (Table 3). Un-
der the same conditions, (E)-3,3Ј,4,5Ј-tetrahydroxystilbene
(15; piceatannol) was isolated in 45% yield after chromato-
graphic separation from the symmetrical stilbenes 9 and 10.
First, we carried out the ethenolysis of compound 5 in
the presence of complex 1 (Scheme 5). Irrespective of the
ethylene pressure applied (1–5 bar) and the solvent used
(toluene or THF), large amounts of unconverted starting
material were always recovered and the yield of 4-meth-
oxystyrene did not exceed 24% after 2 h at 110 °C. A con-
trol experiment with unsubstituted (E)-stilbene gave similar
results, indicating that the poor solubility of the dimethoxy
derivative 5 in organic solvents is not solely responsible for
the low reactivity observed. A more likely explanation is the
rapid deactivation of the catalyst in the presence of ethyl-
ene. Indeed, mechanistic studies by Grubbs and co-workers
have shown that (methylidene)ruthenium species are the le-
ast stable intermediates in most metathesis reactions initi-
ated by 1 and 2.[23] Other authors have also pointed out the
difficulty in achieving satisfactory conversions in the ethen-
olysis of methyl oleate using Grubbs’ catalysts.[24] In the
light of these results, we decided to switch our attention
to the recycling of homodimer 5 by CM. Thus, (E)-4,4Ј-
dimethoxystilbene was treated with 1 equiv. of 3,5-dimeth-
Scheme 6. Synthesis of resveratrol (14) and piceatannol (15) by
cross-metathesis catalyzed by ruthenium complex 1.
In order to obtain resveratrol with a high selectivity com-
oxystyrene in refluxing toluene containing 5 mol-% of cata- pared to the corresponding homoproducts, we performed a
lyst 1. After 1 h, equilibrium was reached and we were ple- cross-metathesis of 3,5-dihydroxystyrene catalyzed by com-
ased to note that protected resveratrol 6 was the major pro- plex 1 using a tenfold excess of p-hydroxystyrene (Table 3).
duct in the reaction mixture (55%), together with 4-meth- This reaction afforded a 94% overall yield of coupling
oxystyrene (12%) and starting materials (26% and 7% of products, out of which resveratrol (14) contributed to the
the stilbene and the styrene, respectively).
remarkable extent of 95% and was therefore isolated in
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Stereoselective Synthesis of (E)-Hydroxystilbenoids
Table 3. Synthesis of resveratrol (14) and piceatannol (15) by cross-metathesis catalyzed by ruthenium complex 1.
FULL PAPER
Styrenes
Equiv.
Cross-product
Isolated yield
[%]
Product distribution
[%]
4-Hydroxystyrene
3,5-Dihydroxystyrene
1
1
14
14
15
87
94
86
8/14/9
23:60:17
4-Hydroxystyrene
3,5-Dihydroxystyrene
10
1
8/14/9
0:95:5
3,4-Dihydroxystyrene
3,5-Dihydroxystyrene
1
1
10/15/9
26:52:22
of ruthenium catalyst 1 (0.03 mmol) in dry toluene or THF (1 mL)
under an inert gas. The mixture was refluxed under Ar for 1 h. It
was then cooled to room temperature and filtered through Celite®.
The filtrate was concentrated under vacuum and purified by flash
column chromatography on silica gel using acetone as eluent. The
structure of the resulting pure stilbene product was confirmed by
1H NMR spectroscopy.
89% yield after purification. (E)-3,3Ј,5,5Ј-Tetrahydroxystil-
bene (9) accounted for the remaining 5% of the product
distribution, while the formation of (E)-4,4Ј-dihydroxystil-
bene (8) was totally suppressed.
Conclusion
Typical Procedure for Heterocoupling: A solution of styrene A
(1 mmol) and styrene B (1 mmol) in dry toluene or THF (2 mL)
was added to a solution of ruthenium catalyst 1 (0.03 mmol) in dry
toluene or THF (1 mL) under an inert gas. The mixture was re-
fluxed under Ar for 1 h. It was then cooled to room temperature
In this study we have shown that the (N-heterocyclic car-
bene)ruthenium complex 1 efficiently catalyzes the cross-
coupling of various substituted styrenes into polymethoxy-
and polyhydroxystilbenes with an excellent (E)-selectivity
for the newly formed C=C double bonds. Selectivity toward and filtered through Celite®. The filtrate was concentrated under
vacuum and fractioned by column chromatography on silica gel
using a 98:2 (v/v) n-heptane/acetone mixture as eluent. The struc-
tures of the pure homocoupling and cross-coupling products were
the mixed-coupling products can be enhanced by introduc-
ing one of the reaction partners in excess. Although the
homodimer by-products display interesting biological ac-
tivities on their own, we have examined the possibility of
recycling them. We have also established that the presence
of phenolic functions does not hinder the metathesis
reaction, thereby allowing the direct synthesis of polyhy-
droxystilbenes with no preliminary protection step. These
results are a good foundation for future developments, and
we are currently searching for new catalysts that should be
more selective toward the mixed cross-products.
1
confirmed by H NMR spectroscopy.
Typical Procedure for Ethenolysis: A glass pressure reactor was
charged with
a
stilbene (1 mmol), ruthenium catalyst
1
(0.03 mmol), and dry toluene (2 mL) under an inert gas. It was
then pressurized with ethylene (5 bar). The mixture was stirred in
an oil bath at 110 °C for 2 h and then cooled to room temperature
and filtered by suction. The filtrate was analyzed by GC using n-
dodecane as an internal standard.
(E)-4,4Ј-Dimethoxystilbene (5):[27,28] White powder. 1H NMR
3
(250 MHz, [D6]acetone, 25 °C): δ = 7.64 (d, JH,H = 8.8 Hz, 4 H,
3
Ar), 7.19 (s, 2 H, =CH), 7.07 (d, JH,H = 8.8 Hz, 4 H, Ar), 3.95 (s,
Experimental Section
6 H, OMe) ppm.
General Information: All reactions were performed under argon
using standard Schlenk techniques. Solvents were freshly distilled
from standard drying agents and kept under argon. NMR spectra
1
(E)-3,4Ј,5-Trimethoxystilbene (6):[5,7,29,30] White powder. H NMR
3
(250 MHz, [D6]acetone, 25 °C): δ = 7.66 (d, JH,H = 8.7 Hz, 2 H,
3
3
1
Ar), 7.34 [d, JH,H (E) = 16.4 Hz, 1 H, =CH], 7.16 [d, JH,H (E) =
were recorded with a Bruker AM250 or DSX400 spectrometer. H
3
16.3 Hz, 1 H, =CH], 7.07 (d, JH,H = 8.8 Hz, 2 H, Ar), 6.91 (d,
NMR chemical shifts are listed in ppm downfield from TMS. Gas
chromatography (GC) was carried out with a Varian 3900 system
equipped with a Chrompack CP-Sil 5 CB capillary column (15 m
length, 0.25 mm diameter, 0.25 μm film thickness). Microanalyses
were performed by the “Centre de Microanalyse du CNRS” at Ver-
naison, France.
4JH,H = 2.2 Hz, 2 H, Ar), 6.57 (t, JH,H = 2.2 Hz, 1 H, Ar), 3.96
4
(s, 6 H, OMe), 3.93 (s, 3 H, OMe) ppm.
(E)-3,3Ј,5,5Ј-Tetramethoxystilbene (7):[7,27,31] White powder. 1H
NMR (250 MHz, [D6]acetone, 25 °C): δ = 7.32 (s, 2 H, =CH), 6.91
(d, 4JH,H = 2.2 Hz, 4 H, Ar), 6.56 (t, 4JH,H = 2.1 Hz, 2 H, Ar), 3.95
(s, 12 H, OMe) ppm.
Starting Materials: The ruthenium complexes [RuCl2(=CHPh)(SI-
Mes)(PCy3)] [second-generation Grubbs catalyst 1; SIMes = 1,3-
bis(2,4,6-trimethylphenyl)imidazolidin-2-ylidene], [RuCl2(=CHPh)-
(PCy3)2] (Grubbs catalyst, 2), and [RuCl2{=C(H)C6H4(OiPr)}-
(SIMes)] (Hoveyda–Grubbs catalyst, 3) were purchased from
Strem. 4-Hydroxystyrene was obtained by demethylation of 4-
methoxystyrene with ethanethiol/sodium hydride in DMF.[25] Other
substituted styrene derivatives were obtained by Wittig reaction be-
tween the corresponding benzaldehyde and methyltriphenylphos-
phonium bromide.[26]
(E)-4,4Ј-Dihydroxystilbene (8):[7] White powder. 1H NMR
(250 MHz, [D6]acetone, 25 °C): δ = 8.74 (s, 2 H, OH), 7.53 (d, 3JH,H
3
= 8.6 Hz, 4 H, Ar), 7.10 (s, 2 H, =CH), 6.97 (d, JH,H = 8.6 Hz, 4
H, Ar) ppm.
(E)-3,3Ј,5,5Ј-Tetrahydroxystilbene (9):[7,31,32] Pale-pink powder. 1H
NMR (400 MHz, [D6]acetone, 25 °C): δ = 8.27 (br. s, OH), 6.92 (s,
4
4
2 H, =CH), 6.54 (d, JH,H = 2.1 Hz, 4 H, Ar), 6.28 (t, JHH
=
2.1 Hz, 2 H, Ar) ppm.
Typical Procedure for Homocoupling:
(1 mmol) in dry toluene or THF (2 mL) was added to a solution
A
solution of styrene
(E)-3,3Ј,4,4Ј-Tetrahydroxystilbene (10):[32] White powder. 1H NMR
(400 MHz, [D6]acetone, 25 °C): δ = 8.35 (br. s, OH), 7.04 (d, JH,H
4
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K. Ferré-Filmon, L. Delaude, A. Demonceau, A. F. Noels
FULL PAPER
= 2.0 Hz, 2 H, Ar), 6.91 (s, 2 H, =CH), 6.85 (dd, 3JH,H = 8.0, 4JH,H
= 2.1 Hz, 2 H, Ar), 6.79 (d, JH,H = 8.1 Hz, 2 H, Ar) ppm.
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3
(E)-4,4Ј-Dihydroxy-3,3Ј-dimethoxystilbene (11):[33] Colorless crys-
tals from CH2Cl2/MeOH. 1H NMR (400 MHz, CDCl3, 25 °C): δ
4
3
= 7.02 (d, JH,H = 2 Hz, 2 H, Ar), 7.00 (dd, JH,H = 8.2 Hz, 2 H,
3
Ar), 6.90 (d, JH,H = 8 Hz, 2 H, Ar), 6.89 (s, 2 H, =CH), 5.61 (s, 2
H, OH), 3.95 (s, 6 H, OMe) ppm.
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(E)-3,3Ј,4,4Ј-Tetrakis(trimethylsilyloxy)stilbene (12): Pale-green so-
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1130–1136.
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3
6.79 (d, JH,H = 8.8 Hz, 2 H, Ar), 6.76 (s, 2 H, =CH), 1.01 (s, 18
H, SiMe3), 0.99 (s, 18 H, SiMe3) ppm. 13C NMR (100 MHz, [9] a) R. R. Schrock, J. S. Murdzek, G. C. Bazan, J. Robbins, M.
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CDCl3, 25 °C): δ = 146.9, 145.6, 131.5, 126.7, 121.2, 119.8, 118.9,
26.03 (SiMe3), 26.00 (SiMe3) ppm. C26H44O4Si4 (532.97): calcd. C
58.59, H 8.32; found C 58.51, H 8.36.
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1
(E)-4-Hydroxy-4Ј-methoxystilbene (13):[34] Pink powder. H NMR
3
(250 MHz, [D6]acetone, 25 °C): δ = 8.51 (br. s, OH), 7.62 (d, JH,H
= 8.8 Hz, 2 H, Ar), 7.55 (d, 3JH,H = 8.7 Hz, 2 H, Ar), 7.20 [d, 3JH,H
(E) = 16.2 Hz, 1 H, =CH], 7.08 [d, 3JH,H (E) = 16.1 Hz, 1 H, =CH],
3
3
7.05 (d, JH,H = 8.8 Hz, 2 H, Ar), 7.00 (d, JH,H = 8.7 Hz, 2 H,
Ar), 3.94 (s, 3 H, OMe) ppm.
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powder. H NMR (400 MHz, [D6]acetone, 25 °C): δ = 8.45 (br. s,
3
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(E)-3,3Ј,4,5Ј-Tetrahydroxystilbene (Piceatannol, 15):[29,35] Pale-yel-
low powder. 1H NMR (400 MHz, [D6]acetone, 25 °C): δ = 8.20 (br.
4
3
s, OH), 7.07 (d, JH,H = 2.1 Hz, 1 H, Ar), 6.95 [d, JH,H (E) =
3
4
16.2 Hz, 1 H, =CH], 6.90 (dd, JH,H = 8.1, JH,H = 2.1 Hz, 1 H,
Ar), 6.82 [d, JH,H (E) = 16.2 Hz, 1 H, =CH], 6.80 (d, JH,H
8.1 Hz, 1 H, Ar), 6.52 (dd, JH,H = 2.1, JH,H = 1.0 Hz, 2 H, Ar),
6.25 (dd, JH,H = 2.1, JH,H = 1.1 Hz, 1 H, Ar) ppm.
3
3
=
4
4
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4
4
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Acknowledgments
The financial support of the EU, through grant TMR-HPRN CT
2000-10 “Polycat”, is gratefully acknowledged.
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