Cobalt-catalyzed vinylation of aromatic halides using β-halostyrene: Experimental and DFT studies

Article abstract of DOI:10.1021/jo3005149

A new protocol for the direct cobalt-catalyzed vinylation of aryl halides using β-halostyrene has been developed in order to form functionalized stilbenes. A variety of aromatic halides featuring different reactive group were employed. This method proceeded smoothly with a total retention of the double bond configuration in the presence of triphenylphosphine as ligand. Preliminary DFT calculations rationnalize these results and proposed a reaction pathway in agreement with the experimental conditions. This procedure offers a new route to the stereoselective synthesis of stilbenes.

Full text of DOI:10.1021/jo3005149

Article
pubs.acs.org/joc
Cobalt-Catalyzed Vinylation of Aromatic Halides Using
β‑Halostyrene: Experimental and DFT Studies
Aurelien Moncomble,† Pascal Le Floch,†,§ Agusti Lledos,‡ and Corinne Gosmini*,†
́
†Laboratoire Het
́
er
́
oel
́
em
́
ents et Coordination, Ecole Polytechnique, CNRS, Route saclay, 91128 Palaiseau Cedex, France
‡Departament de Química, Edifici C.n Universitat Auton
̀
oma de Barcelona, 08193 Bellaterra, Catalonia, Spain
S
* Supporting Information
ABSTRACT: A new protocol for the direct cobalt-catalyzed
vinylation of aryl halides using β-halostyrene has been
developed in order to form functionalized stilbenes. A variety
of aromatic halides featuring different reactive group were
employed. This method proceeded smoothly with a total
retention of the double bond configuration in the presence of
triphenylphosphine as ligand. Preliminary DFT calculations rationnalize these results and proposed a reaction pathway in
agreement with the experimental conditions. This procedure offers a new route to the stereoselective synthesis of stilbenes.
of aromatic halides by electrochemical28 and chemical29 ways
using vinyl acetates.
INTRODUCTION
■
Stilbenes are natural compounds ubiquitous in plants.1 Many
compounds such as resveratrol2 and combretastatin A-43 have
been isolated and are used for their antitumoral,4 anti-
inflammatory,5 neuroprotectiv,e6 and cardioprotective7 proper-
ties. Moreover, structure−activity studies have shown that the
configuration (Z or E) of the compound is essential for their
properties.8
Herein, we report a new Co(II)-mediated cross-coupling
reaction devoted to the generalization of these reactions to the
direct vinylation of aromatic halides using the very reactive β-
bromostyrene. The control of its reactivity and the retention of
the double bond configuration are important problems that
were addressed. Moreover, a mechanism is proposed for this
new cobalt-catalyzed reaction based on the experimental results
and DFT calculations.
Many studies deal with the synthesis of these compounds,
forming either the double bond or one of the two
corresponding single bonds. The double bond was formed by
retro [2 + 2] cycloaddition such as Wittig,9 Peterson,10 or
Julia11 reactions or from an acetylenic compound by
heterogeneous12 or homogeneous13 reduction or hydro/
carbometalation14 or by metathesis reactions.15 One of the
single bond can result from a Mizoroki−Heck reaction16 or a
metal-catalyzed cross-coupling reaction. These last reactions
have been extensively studied with palladium- or nickel-based
catalysts,17 involving a vinyl halide and an aryl metal
compound18 or conversely an aryl halide and a vinyl metal
compound.19 Some other catalysts were used with success:
rhodium,20 iron,21 manganese,22 and cobalt23 especially. All of
the reactions described above deal with the synthetic difficulties
associated with the preparation of the organometallic reagent
especially when its organic precursor bears a reactive group.
Therefore, to avoid this step, some direct cross-coupling
reactions were developed by electrochemical or chemical
processes to form stilbenes, but to the best of our knowledge,
this domain remains under investigated.
RESULTS AND DISCUSSION
■
Experimental Studies. Having successfully developed
methods using CoBr2/PPh3/Mn system for the direct and
selective synthesis of unsymmetrical biaryls, we first inves-
tigated these initial optimized conditions.30 This preliminary
study involving this system in a mixture of DMF/pyridine at 50
°C was highly encouraging (57% GC yield) with 2 equiv of β-
bromostyrene and 1 equiv of phenyl iodide. We then optimized
the reaction conditions: modification of the solvent, addition of
cosolvents such as pyridine, change of the ligand, and the
temperature.
According to all our previous studies, the reaction carried out
in toluene or THF did not work: the reagents were recovered.
The best results were obtained in the presence of
[CoBr2(PPh3)] as catalyst, using acetonitrile in place of DMF
without any pyridine, leading to a 75% isolated yield (Scheme
1).
No improvement was observed in the absence of ligand or in
the presence of 2,2′-bipyridine instead of PPh3. Some other
parameters such as the nature and amount of the reductant and
the relative amounts of reagents were modified but without any
improvement. The same yield was obtained at room temper-
Our team has already encountered some successes in direct
cobalt-catalyzed reactions.24 This cheap and nontoxic metal
allowed us to form organometallic species25 and many kinds of
carbon−carbon bonds26 in a simple manner. Among them, we
have already performed double bond formations using cobalt-
based catalysts such as the Heck reaction27 and the vinylation
Received: March 13, 2012
Published: May 16, 2012
© 2012 American Chemical Society
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Scheme 1. Cobalt-Catalyzed Direct Vinylation of Phenyl
Iodide with β-Bromostyrene
Table 2. Effect of the Ligand on the Vinylation of Ethyl
Bromobenzoate
a
a
a
a
ArH
ArBr
ArVin
(%)
ArAr
entry
ligand
(%)
(%)
(%)
1
2
3
4
5
6
7
12
1
0
0
27
61
44
14
23
0
b
PPh3 (1 equiv)
PPh3 (2 equiv)
dppe
55
c
16
9
40
15
70
0
30
53
16
8
ature instead of 50 °C, but the reaction rate decreased (19 h
instead of 3 h).
Then various aryl iodides reacted in these optimized
conditions (Scheme 2). Results are reported in Table 1. Yields
dppp
18
28
8
bipyridine
64
1
d
diazadiene
41
40
a
b
c
GC yield. Isolated yield. Identical results with a preformed
complex. 1,4-Bis(m-xylyl)-1,3-diazadiene.
d
Scheme 2. Cobalt-Catalyzed Direct Vinylation of Aryl
Iodides with β-Bromostyrene
dimerized (Table 2, entries 4 and 5). This effect is particularly
enforced with dppp. Nitrogen ligands brought no improvement
(Table 2, entries 6 and 7). Under these conditions (1 equiv of
ArBr vs β-bromostyrene), yields were moderate even with PPh3
due to the formation of ArAr. Thus, we have decided to
introduce an excess of aryl halide (2 equiv vs β-bromostyrene),
and we have extended the reaction to various bromides
(Scheme 4, Table 3).
were good except for an activated aryl iodide such as methyl-4-
iodoobenzoate. In this case, the dimerization of the starting
material seems to be too rapid.
Satisfactory to very good yields were rapidly obtained under
these conditions (the reaction was complete at the end of the
addition). Remarkably, ortho-substituted aromatic compounds
are especially well-suited for this reaction: their low reactivity in
the dimerization reaction led to a better availability of this
reagent for the cross-coupling reaction (Table 3, entries 3, 5, 8,
and 12).
In the case of less reactive compounds such as β-
chlorostyrene, diminution of the addition rate was required
to allow reaction (Scheme 5). The cross-coupling of p-
EtOCOC6H4Br or p-MeOC6H4Br with β-chlorostyrene led to
similar isolated yields: 73% of the corresponding coupling
products in 16 min or 72% in 20 min, respectively.
Table 1. Cobalt-Catalyzed Direct Vinylation of Aryl Iodides
with β-Bromostyrene in One Pot: Substrate Scope
a
entry
ArI
yield (%)
duration
1
2
3
p-MeOC6H4I
C6H5I
66
3 h
75
2 h 45
45 min
p-MeOCOC6H4I
(49)
a
Isolated yield (GC yield).
We then envisaged the use of readily available poorly reactive
aryl bromides (as opposed to the corresponding iodides) which
would be a great extension of this reaction. In the previously
optimized conditions with 2 equiv of β-bromostyrene, only
10% GC yield of styrene was detected. The two homocoupling
products were formed in majority.
Satisfactory results were obtained by a dramatic change in the
experimental conditions. In order to limit the dimerization of
the more reactive halide (β-bromostyrene), it was added
dropwise in the reaction mixture. By this procedure, β-
bromostyrene remains in low concentration and cannot
dimerize. Moreover, this allows us to remove the excess of
the vinyl halide.
We then optimized many reaction parameters concerning the
reaction between β-bromostyrene and ethyl 4-bromobenzoate
(among them, the volume of solvent in which the β-
bromostyrene is diluted and the duration of the addition),
the screening of ligands was carried out, and the results are
reported in Table 2.
Under the conditions described in Scheme 3, PPh3 was
replaced by some simple ligands, including 2,2′-bipyridine,
dppp, dppe, and 1,4-bis(m-xylyl)-1,3-diazadiene. However, the
most encouraging results were obtained with PPh3.
Aiming to study the stability of the double bond during the
coupling process, we used the cis-β-bromostyrene prepared
according to a previously described procedure.31 A total
retention of the double bond configuration was observed
under these conditions (Scheme 6).
Mechanistic Studies. After this experimental study, we
wanted to rationalize these results by a mechanistic study. The
study was focused on the typical reaction of trans-β-
bromostyrene (vinylic compound, represented by Vin-Br in
schemes) with bromobenzene (aromatic compound, repre-
sented by Ph-Br in schemes). According to our previous
mechanism on cobalt-catalyzed dimerization of aromatic
halides,32 involving a CoII(PPh3)2Br2, a catalytic cycle for this
new reaction was expected. First, a preliminary reduction step
of the CoII precursor in CoI active species is proposed. This
species is then involved in an oxidative addition of a halide
(either vinylic or aromatic) leading to a CoIII species, which is
reduced in the following step by heterogeneous manganese to
afford a new CoI species that is involved in another oxidative
addition with another halide (respectively with either aromatic
or vinylic). The cycle is closed by a reductive elimination
releasing both the CoI catalytic species and the coupling
product.
The presence of a ligand was necessary (Table 2, entry 1),
and the best one was commercial triphenylphosphine (Table 2,
entry 2). It should be noted that the introduction of 2 equiv of
triphenylphosphine did not lead to any improvement, and there
was no significant difference with the preformed complex
(Table 2 entry 3). With bidentate phosphine ligands, the
aromatic halide reacted more slowly and the β-bromostyrene
This mechanism accounts for the formation of three main
products: the cross-coupling product (obtained by the
consecutive oxidative addition of two different reagents in
any order) and the dimers of each starting materials of the
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Scheme 3. Cobalt-Catalyzed Direct Vinylation of Phenyl Iodide with β-Bromostyrene
obtained by X-ray diffraction for the [CoBr2(PPh3)2] complex34
and the good reproduction of spin states (see the Supporting
Information for more details). A good reproduction of the
geometry was achieved by some GGA exchange-correlation
functionals. However, the best results were obtained by the use
of the OPBE functional (GGA type, using the OPTX exchange
functional35 and the PBE correlation functional36). Moreover,
this functional has given good results in the description of spin
states of metal complexes as described with iron complexes37
validating our choice. To save computation time, a two-level
description procedure was used: optimization were realized
using a D1 description level constituted by the Stuttgart−
Dresden relativistic pseudopotential and associated basis set for
cobalt, 6-31G* for all nonmetallic atoms except carbon and
hydrogen not linked to phosphorus in phenyl rings which have
been described by 3-21G*. Energies were then computed on
the basis of these geometries with single-point computations
using the D2 description level constituted of all-electron Def2-
QZVP basis set for cobalt and 6-311+G** for all non metallic
atoms. The solvent of the reaction (acetonitrile) was taken into
account in single-point computations by a continuum model,
using the C-PCM model as implemented in Gaussian 03 (see
the Supporting Information for more precisions). This
procedure is referred as OPBE/D2//OPBE/D1.
Scheme 4. Cobalt-Catalyzed Direct Vinylation of Aryl
Bromides with β-Bromostyrene
Table 3. Cobalt-Catalyzed Direct Vinylation of Various Aryl
Bromides with β-Bromostyrene
a
entry
ArBr
yield (%)
duration (min)
1
2
p-EtOCOC6H4Br
p-CF3C6H4Br
o-CF3C6H4Br
p-CNC6H4Br
o-CNC6H4Br
p-Me-COC6H4Br
p-FC6H4Br
68
71
84
64
82
69
71
74
69
75
70
73
10
10
30
15
10
15
10
40
20
10
10
15
3
4
5
6
7
8
o-CH3C6H4Br
C6H5Br
9
10
11
12
p-MeOC6H4Br
m-MeOC6H4Br
o-MeOC6H4Br
a
Isolated yield.
The first part of our work consisted of the study of the
catalytic species. Preliminary computations show that opti-
mization of a catalytic entity featuring two phosphines led to
dissociation of one of the phosphine during the aryl bromide
oxidative addition step. On the other hand, the addition of the
vinyl bromide did not lead to the departure of one of the
phosphines. These results lead us to two conclusions.
Scheme 5. Cobalt-Catalyzed Direct Vinylation of Aryl
Bromides with β-Chlorostyrene
First, in the case of the reaction with dppp ligand or with 2
equiv of phosphines vs cobalt (where the two dimers are mostly
obtained), the necessity for cobalt to be linked to two
phosphines slows the oxidative addition of cobalt in the C−
Br bond. Therefore, the vinyl halide dimerizes first, followed by
the aryl halide, decreasing the cross-coupling yield.
Scheme 6. Cobalt-Catalyzed Direct Vinylation of Ethyl 4-
Bromobenzoate with cis-β-Chlorostyrene
Second, in the cases where a cross-coupling reaction takes
place, another catalytic species should be proposed.
The complexity of the reaction mixture (involving both
heterogeneous manganese and paramagnetic species such as
cobalt) forbids an experimental study based on analytical
methods such as NMR. Moreover, these systems are only
sparsely studied. So, the literature did not give any clues to
understand the nature of the species in our conditions. So we
were bound to a purely theoretical investigation of the system.
We proceeded to undertake an exhaustive study of
[CoBrx(PPh3)n(MeCN)m] complexes (with n + m ≤ 3 and x
= 1 or 2) and found that when x = 1 and x = 2 the most stable
complex is the heterobiliganded one: [CoBrx(PPh3)(MeCN)].
It indicates that the reduction of the most stable complex
obtained leads to the most stable catalytic species. Thus, it
seems reasonable to propose the involvement of [CoBr(PPh3)-
(MeCN)] as the catalytic species.
reaction (obtained by the addition of the same reagent twice on
the metal center in a catalytic cycle).
In order to check our proposal, theoretical investigations
were conducted. To achieve a good description of the system, a
DFT-based study was initiated. DFT-based methods present a
good compromise between the computation time required, the
precision and the reliability of the results obtained in the study
of metal-catalyzed reactions.33 Many exchange-correlation
functionals and basis set were evaluated to achieve the best
characterization of our system. Two parameters were especially
investigated such as the good reproduction of the structure
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We then had to rule out some alternative mechanisms. First,
a conceivable mechanism involving a intermediate RMnX
species did not fit with the experimental conditions (the
reaction conducted in the presence of acetic anhydride did not
lead to any measurable amount of ketone),38 which has already
previously been described in our cobalt-catalyzed reductive
process. Second, the possible involvement of radical species was
both experimentally and theoretically investigated. Addition of
galvinoxyl free radical in the medium did not change the
reaction rate, and computation of the reaction energy
(activation energy of this reaction was not computed) shows
that the radical dissociation is about 10 kcal mol−1 over the
activation energy of the oxidative addition proposed in our
mechanism.
With these data in hand, we were able to compute the
catalytic cycle using the previously modelization depicted above
([CoBr(PPh3)(MeCN)] as initial active and PhCHCHBr
and PhBr as substrates). The reduction steps by manganese
were not computed because of the difficult calculation of a
probably heterogeneous process, but these steps are supposed
to be fast and should not therefore be rate determining.
Calculations were carried out both for the triplet and singlet
spin state. The computed data are given for the first oxidative
addition in the cases of bromobenzene and β-bromostyrene
(Figure 1) and a typical example for the reaction involving
Figure 2. Energy profile in acetonitrile (C-PCM) for the second stage
of the reaction from III-Ph to I (release of stilbene).
Figure 3. Schematic representation of the activation energies (C-PCM
model, data in kcal mol−1) for each stage of the reaction.
Figure 1. Energy profile in acetonitrile (C-PCM) for the first oxidative
addition of respectively Ph-Br and Vin-Br on I.
Moreover, the difference between the activation energies for
the steps involving β-bromostyrene (e.g., 19.4 kcal mol−1 for
the first oxidative addition) and bromobenzene (23.2 kcal
mol−1 for the same step), respectively, reflects the difference of
reactivity experimentally observed between these two species.
The second stage of the reaction (second oxidative addition
and reductive elimination) was investigated from the two
reduced products obtained after the first stage. The Figure 3
represents the four possible ways with the activation energies of
each stage (first stage, first oxidative addition; second stage,
second oxidative addition and reductive elimination). More
details are given in the Supporting Information.
successively the addition of bromobenzene and β-bromostyrene
illustrating the second stage of the reaction (second oxidative
addition from III and reductive elimination) (Figure 2).
Converse to what we observed in the case of the dimerization
of aryl halides, spin surfaces are very close to each other. These
results led us to the determination of minimum energy crossing
points (MECP) using the procedure described by Harvey.39
The MECP were determined at the D2 level of description to
ensure a good convergence of the geometry. We have been able
to show that their presence did not have any influence on the
reactivity (see the Supporting Information for more details) so
for clarity they will not be represented in the following
schemes.
Some general features are observed: the oxidative addition
steps are the rate determining steps, the formation of the C−C
bond is nearly barrierless, and it is the driving force of the
reaction. These results are qualitatively the same than those
obtained in our previous studies concerning the formation of
biaryls.
These results allow to explain the formation of the main
products in the reaction conditions.
When all products in the medium are present in comparable
concentrations (one-pot conditions), the most favorable
pathway is the one with the lowest activation energies (upper
pathway on the figure): it leads to the dimerization of the β-
bromostyrene. Once the vinylic compound consumed, the
bromobenzene dimerizes as it is the only reactant in the
medium. This is consistent with our observations: under these
conditions, very small amounts of cross-coupling products are
obtained, the main products being the two dimers.
The energy of the oxidative addition steps (from 7.7 to 23.2
kcal mol−1) (see Figure 3) are low enough to account for the
rapid reaction in the experimental conditions (50 °C).
Conversely, when the vinylic compound is added dropwise,
its concentration in the medium remain low which slows its
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Figure 4. Energy profile in acetonitrile (C-PCM) for the comparative study of the isomerization of III-Vin and its transformation in IV.
oxidative addition. The addition of the aromatic moiety (in very
large excess) on the catalyst is competitive in this case. This
result is in line with the results previously published by
Amatore, Jutand, and Torii40 in the case of palladium-catalyzed
reductive biaryls formation. Two pathways should account for
the formation of the key complex [Co(Vin-trans)(Ph)Br]:
either the consecutive addition of bromobenzene and β-
bromostyrene or the reverse order.
zene and β-bromostyrene is reported in Scheme 7 according to
our experimental and DFT studies.
Scheme 7. Corrected Mechanism for the Cobalt-Catalyzed
Reaction between Bromobenzene and β-Bromostyrene
To discriminate between these two possibilities, we
investigated the trans−cis isomerization of the cobalt−vinylic
species [CoI(Vin-trans)(PPh3)(MeCN)]. If we assume that the
first oxidative addition step entails the addition of bromostyr-
ene, the cobalt−vinylic species [CoI(Vin-trans)(PPh3)-
(MeCN)] (III-vin) should be present after the first oxidative
addition/reduction steps. A trans−cis isomerization could take
place in this intermediate giving an isomer with a cis Co/Ph
arrangement. The transition state for the isomerization of
[CoI(Vin-trans)(PPh3)(MeCN)] to [CoI(Vin-cis)(PPh3)-
(MeCN)] was located. This activation barrier is low enough
to allow isomerization (as for the mechanisms exposed earlier).
Note that MECP were found, but their positions did not
change the relative energies of the reactions involved.
This transition state (central one on the figure 4) is lower
than those corresponding to the oxidative addition for both
compounds and corresponds to a rapid reaction. As we have
shown in the Experimental Section that no isomerization is
observed during this reaction both from cis and trans
compounds, the pathway involving the species allowing this
[CoIVin(PPh3)(MeCN)] complex can be ruled out. It leads us
to the result that in the case of dropwise addition of the vinylic
species, the oxidative addition of the vinylic moiety follows the
addition of the aromatic one, avoiding an intermediate in which
isomerization should take place.
The involved mechanism in the dropwise conditions is then
one of those starting from the III-Ph species. The formation of
the cross-coupling product can be explained by the mechanism
involving the oxidative addition of the aromatic compound and,
in a second step, the addition of the vinylic fragment. The result
involving the [CoIPh(PPh3)(MeCN)] species is consistent with
the presence in the reaction medium of the dimer of the
aromatic species.
CONCLUSIONS
■
In conclusion, we have described a new and simple method for
the preparation of stilbene derivatives by a reductive
heterocoupling under cobalt catalysis. In this protocol, the
procedure of addition of the reagents is crucial in determining
the final coupling products.
The reaction can be carried out under mild conditions and
affords satisfactory to very good yields. The total retention of
the double bond was preserved. Moreover, the modelization of
the reaction by DFT methods allowed us to propose two
reaction pathways compatible with the experimental conditions
depending on the experimental conditions. A good agreement
was found between experimental results and mechanistic
propositions.
A corrected mechanism (involving MeCN instead of PPh3 as
ligand) for the cobalt-catalyzed reaction between bromoben-
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(E)-Stilbene:44 as a colorless solid [CAS no. 103-30-0] (0.311 g,
69%); H NMR (300 MHz, CDCl3) δ 7.62 (dd, 4H, J = 8.5 Hz, 1.3
These new results encourage us to extend cobalt catalysis to
diverse substrates in a near future.
1
Hz), 7.44 (tt, 4H, J = 7.3 Hz, 1.5 Hz), 7.34 (tt, 2H, J = 7.4 Hz, 1.3 Hz),
7.22 (s, 2H); 13C NMR (75 MHz, CDCl3) δ 137.5, 128.8, 128.7,
127.7, 126.7.
EXPERIMENTAL SECTION
■
(E)-4-Methoxystilbene:45 colorless solid [CAS no. 1694-19-5]
Typical procedure for the coupling of halostyrene with aryl bromide:
to a solution of CoBr2 (10 mol %, 0,25 mmol, 55 mg),
triphenylphosphine (10 mol %, 0,25 mmol, 65 mg), and manganese
powder (10 mmol, 550 mg) in acetonitrile (6 mL) was added at 50 °C
aryl bromide (2 equiv, 5 mmol). A solution of bromostyrene (1 equiv,
2,5 mmol, 320 μL) in acetonitrile (2 mL) was added dropwise.
Immediately after the addition began, the reaction mixture was
vigorously stirred and trifluoroacetic acid (100 μL) added, causing a
color change to dark gray. When the addition was over, the reaction
mixture was hydrolyzed by hydrochloric acid (2 M) and extracted with
dichloromethane. The organic layer was filtered and dried over
MgSO4. The amount of the cross-coupling product was measured by
GC using an internal reference (tetradecane, 100 μL). The reaction
was repeated for several addition rates, and the reaction with the best
yield (reported in Table 3) was treated by evaporation of the solvent
and purification by column chromatography on silica gel (petroleum
ether/diethyl ether). The coupling product was characterized by NMR
(1H and 13C).
1
(0.394 g, 75%); H NMR (300 MHz, CDCl3) δ 7.51 (d, 2H, J = 7.2
Hz), 7.46 (d, 2H, J = 8.6 Hz), 7.35 (t, 2H, J = 7.3 Hz), 7.24 (t, 1H, J =
7.2 Hz), 7.18 (d, 1H, J = 16.5 Hz), 6.98 (d, 1H, J = 16.4 Hz), 6.90 (d,
2H, J =8.7 Hz), 3.81 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 159.6,
137.8, 130.3, 128.7, 128.3, 127.8, 127.3, 126.6, 126.2, 114.0, 55.1.
(E)-3-Methoxystilbene:47 colorless solid [CAS no. 14064-41-6]
1
(0.368 g, 70%); H NMR (300 MHz, CDCl3) δ 7.50 (d, 2H, J = 7.2
Hz), 7.40−7.35 (m, 2H), 7.25 (m, 2H), 7.18−7.10 (m, 4H), 6.81 (d,
1H, J = 13.4 Hz), 3.84 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 160.8,
139.4, 137.7, 129.9, 129.0, 128.8, 128.5, 127.9, 126.9, 119.7, 113.8,
112.0, 55.7.
(E)-2-Methoxystilbene:49 colorless oil [CAS no. 52805-92-2]
(0.384 g, 73%); 1H NMR (300 MHz, CDCl3) δ 7.68 (dd, 1H, J = 7.8
Hz, 1.9 Hz), 7.62−7.58 (m, 3H), 7.45−7.29 (m, 4H), 7.17 (d, 1H, J =
16.4 Hz), 7.03 (t, 1H, J = 8.0 Hz), 6.98 (d, 1H, J = 8.1 Hz), 3.92 (s,
3H); 13C NMR (75 MHz, CDCl3) δ 157.5, 139.1, 129.8, 129.3, 129.1,
127.9, 127.0, 126.8, 126.7, 124.1, 121.3, 111.5, 56.1.
(Z)-Ethyl-4-styrylbenzoate:50 colorless solid (0.454 g, 72%): H
1
(E)-Ethyl 4-styrylbenzoate:41 colorless solid [CAS no. 109463-
48-1] (0.429 g, 68%); 1H NMR (300 MHz, CDCl3) δ 8.06 (2H, d, J =
8.4 Hz), 7.59 (2H, d, J = 6.8 Hz), 7.56 (2H, d, J = 7.1 Hz), 7.41 (2H, t,
J = 7.5 Hz), 7.33 (1H, m), 7.25 (1H, d, J = 16.2 Hz), 7.15 (1H, d, J =
16.6 Hz), 4.41 (2H, q, J = 7.1 Hz), 1.43 (3H, t, J = 7.1 Hz); 13C NMR
(75 MHz, CDCl3) δ 167.9, 143.2, 138.2, 132.6, 131.5, 130.7, 130.3,
129.7, 129.1, 128.3, 127.8, 62.4, 15.9.
NMR (300 MHz, CDCl3) δ 7.91 (2H, d, J = 8.3 Hz), 7.35 (2H, d, J =
8.4 Hz), 7.26−7.20 (5H, m,), 6.75 (1H, d, J = 12.6 Hz), 6.64 (1H, d, J
= 12.6 Hz), 4.39 (2H, q, J = 6.9 Hz), 1.43 (3H, t, J = 7.0 Hz); 13C
NMR (75 MHz, CDCl3) δ 166.7, 142.5, 137.1, 132.2, 129.7, 129.4,
129.2, 129.0, 128.8, 128.5, 127.7, 61.3, 14.2.
(E)-4-Trifluoromethylstilbene:42 colorless oil [CAS no. 1149-56-
ASSOCIATED CONTENT
■
1
0] (0.440 g, 71%); H NMR (300 MHz, CDCl3) δ 7.63 (3H, s), 7.56
S
* Supporting Information
Copies of 1H NMR and 13C NMR spectra for all the
compounds and computational details. This material is available
free of charge via the Internet at http://pubs.acs.org.
(2H, d, J = 6.8 Hz), 7.54−7.27 (4H, m), 7.23 (1H, d, J = 16.4 Hz),
7.14 (1H, d, J = 16.4 Hz); 13C NMR (75 MHz, CDCl3) δ 141.2, 137.0,
131.6, 129.6 (q, J = 32.5 Hz), 129.2, 128.7, 127.5, 127.2, 127.0, 126.0
(q, J = 3.8 Hz), 124.7 (q, J = 268.1 Hz).
(E)-3-Trifluoromethylstilbene:43 colorless oil (0.521 g, 84%); 1H
NMR (300 MHz, CDCl3) δ 7.77 (d, 1H, J = 6.5 Hz), 7.66 (d, 1H, J =
6.6 Hz), 7.57−7.44 (m, 4H), 7.40−7.23 (m, 4H), 7.08 (d, 1H, J = 15.8
Hz); 13C NMR (75 MHz, CDCl3) δ 137.1, 136.6 (q, J = 2.4 Hz),
132.8, 132.0, 128.9, 128.3, 127.6 (q, J =29 Hz), 127.3, 127.2, 126.9,
125.8 (q, J = 5.8 Hz), 124.7 (q, J = 270 Hz), 124.5 (q, J = 1.9 Hz).
(E)-4-Styrylbenzonitrile:44 colorless solid [CAS no. 13041-79-7]
AUTHOR INFORMATION
Corresponding Author
*E-mail: corinne.gosmini@polytechnique.edu.
■
Notes
The authors declare no competing financial interest.
§Deceased on March 17, 2010.
1
(0.328 g, 64%); H NMR (300 MHz, CDCl3) δ 7.62 (4H, q, J = 8.6
Hz), 7.56 (2H, d, J = 7.2 Hz), 7.48−7.31 (3H, m),7.24 (1H, d, J = 16.3
Hz), 7.11 (1H, d, J = 16.4 Hz); 13C NMR (75 MHz, CDCl3) δ 142.2,
136.7, 132.9, 132.8, 129.3, 129.1, 127.3, 127.3, 127.1, 119.5, 111.0.
(E)-2-Styrylbenzonitrile:45 colorless oil [38175-96-1] (0.421 g,
82%); 1H NMR (300 MHz, CDCl3) δ 7.82 (d, 1H, J = 8.0 Hz), 7.72−
7.65 (m, 1H), 7.61−7.59 (m, 3H), 7.50−7.32 (m, 6H); 13C NMR (75
MHz, CDCl3) δ 140.8, 136.4, 133.6, 133.3, 133.0, 128.6, 128.5, 127.4,
127.2, 125.5, 124.3, 111.5.
ACKNOWLEDGMENTS
We thank the IDRIS for computational facilities and the
■
Minister
̀
e de l’Enseignement Super
́
ieur et de la Recherche for a
grant. A.L. thanks the Spanish MICINN for financial support
(Project No. CTQ2011-23336).
REFERENCES
(E)-4-Acetylstilbene:46 colorless solid [20488-42-0] (0.383 g,
■
1
(1) (a) Chen, T.; Wang, X. N.; Lou, H. X. Nat. Prod. Rep. 2009, 26,
69%); H NMR (300 MHz, CDCl3) δ 7.98 (2H, d, J = 8.4 Hz), 7.61
916−935. (b) Ferre-
́
Filmon, K.; Delaude, L.; Demonceau, A.; Noels,
A. F. Coord. Chem. Rev. 2004, 248, 2323−2336.
(2H, d, J = 8.6 Hz), 7.57 (2H, d, J = 8.0 Hz), 7.41 (2H, t, J = 7.7 Hz),
7.34 (1H, d, J = 7.2 Hz), 7.26 (1H, d, J = 16.3 Hz), 7.15 (1H, d, J
=16.3 Hz), 2.64 (3H, s); 13C NMR (75 MHz, CDCl3) δ 200.3, 144.7,
139.4, 138.7, 134.2, 131.6, 131.6, 131.1, 130.2, 129.6, 129.2, 29.4.
(E)-4-Fluorostilbene:47 colorless solid [CAS no. 718-25-2 ] (0.32
(2) (a) Takaoka, M. Nippon Kagaku Kaishi 1939, 60, 1090−1100.
(b) Chalal, M.; Vervandier-Fasseur, D.; Meunier, P.; Cattey, H.;
Hierso, J.-C. Tetrahedron 2012, 68, 3899−3907.
1
(3) Pettit, G.; Cragg, G. M.; Herald, D. L.; Schmidt, J. M.;
Lobavanijaya, P. Can. J. Chem. 1982, 60, 1347−1376.
g, 71%); H NMR (300 MHz, CDCl3) δ 7.55−7.46 (m, 4H), 7.39 (t,
2H, J = 7.5 Hz), 7.29 (t, 1H, J = 7.4 Hz), 7.13−6.98 (m, 2H), 7.05 (d,
2H, J = 7.4 Hz); 13C NMR (75 MHz, CDCl3) δ 162.5 (d, J = 242 Hz),
137.3, 133.6, 128.9, 128.6, 128.0 (d, J = 7.7 Hz), 127.7, 127.5, 126.5,
115.8 (d, J = 22 Hz).
(4) (a) Jang, M.; Cai; Udeani, G. O.; Slowing, K. V.; Thomas, C. F.;
Beecher, C. W.; Fong, H. H.; Farnsworth, N. R.; Kinghorn, A. D.;
Mehta, R. G.; Moon, R. C.; Pezzuto, J. M. Science 1997, 275, 218−220.
(b) Pettit, G. R.; Singh, S. B.; Boyd, M. R.; Hamel, E.; Pettit, R. K.;
Schmidt, J. M.; Hogan, F. J. Med. Chem. 1995, 38, 1666−1672.
(5) Elmali, N.; Baysal, O.; Harma, A.; Esenkaya, I.; Mizrak, B.
Inflammation 2007, 30, 1−6.
(E)-2-Methylstilbene:48 colorless oil [CAS no. 22257-16-5]
1
(0.360 g, 74%); H NMR (300 MHz, CDCl3) δ 7.67 (d, 1H, J =
7.0 Hz), 7.59 (d, 2H, J = 7.6 Hz), 7.46−7.38 (m, 3H), 7.33−7.22 (m,
4H), 7.06 (d, 1H, J = 16.2 Hz), 2.48 (s, 3H); 13C NMR (75 MHz,
CDCl3) δ 137.8, 136.8, 136.1, 130.8, 130.3,129.0, 127.7, 127.6, 126.8,
126.5, 125.6, 20.4
(6) Karuppagounder, S. S.; Pinto, J. T.; Xu, H.; Chen, L. H.; Flint
Beal, M.; Gibson, G. E. Neurochem. Int. 2009, 54, 111−118.
5061
dx.doi.org/10.1021/jo3005149 | J. Org. Chem. 2012, 77, 5056−5062

The Journal of Organic Chemistry
Article
(7) Gurusamy, N.; Lekli, I.; Mukherjee, S.; Ray, D.; Ahsan, M. K.;
Gherghiceanu, M.; Popescu, L. M. D.; Das, K. Cardiovasc. Res. 2010,
86, 103−112.
2008, 5019−5021. (d) Amatore, M.; Gosmini, C. Chem.Eur. J.
2010, 16, 5848−5852. (e) Begouin, J. M.; Gosmini, C. J. Org. Chem.
2009, 74, 3221−3224. (f) Begouin, J. M.; Claudel, S.; Gosmini, C.
Synlett 2009, 3192−3194. (g) Begouin, J. M.; Rivard, M.; Gosmini, C.
Chem. Commun. 2010, 5972−5974.
(8) Srivastava, V.; Negi, A. S.; Kumar, J. K.; Gupta, M. M.; Khanuja,
S. P. S. Bioorg. Med. Chem. 2005, 13, 5892−5908.
(27) Gomes, P.; Gosmini, C.; Nedelec, J. Y.; Perichon, J. Tetrahedron
Lett. 2002, 43, 5901−5903.
(9) (a) Wittig, G.; Schollkopf, U. Ber. 1954, 87, 1318−1330.
̈
(b) Wittig, G.; Haag, W. Ber. 1955, 88, 1654−1656. (c) Maryanoff, B.
E.; Reitz, A. B. Chem. Rev. 1989, 89, 863−927.
(28) Gomes, P.; Gosmini, C.; Perichon, J. Tetrahedron 2003, 59,
2999−3002.
(10) (a) Peterson, D. J. J. Org. Chem. 1968, 33, 780−784. (b) Ager,
D. J. Synthesis 1984, 5, 384−398.
(29) Amatore, M.; Gosmini, C.; Perichon, J. Eur. J. Org. Chem. 2005,
989−992.
(11) (a) Julia, M.; Paris, J. M. Tetrahedron Lett. 1973, 14, 4833−4836.
(b) Aïssa, C. Eur. J. Org. Chem. 2009, 1831−1844.
(30) Amatore, M.; Gosmini, C. Angew. Chem., Int. Ed. 2008, 47,
2089−2092.
(12) (a) Lindlar, H. Helv. Chim. Acta 1952, 35, 446−450. (b) Brunet,
J. J.; Gallois, P.; Caubere, P. J. Org. Chem. 1980, 45, 1937−1945.
(13) (a) Schrock, R. R.; Osborn, J. A. J. Am. Chem. Soc. 1976, 98,
2143−2147. (b) Sodeoka, M.; Shibasaki, M. J. Org. Chem. 1985, 50,
1147−1149.
(31) Del Ponte, G.; Arcanjo, F. C.; Botteghi, C. J. Mol. Catal. A:
Chem. 2003, 192, 35−40.
(32) Moncomble, A.; Le Floch, P.; Gosmini, C. Chem.Eur. J. 2009,
15, 4770−4774.
(33) Sameera, W. M. C.; Maseras, F. Wiley Interdiscip. Rev. Comput.
Mol. Sci. 2012, 2, 375−385.
(14) (a) Takacs, J. M. In Comprehensive Organometallic Chemistry II;
Abel, E. W., Stone, F. G. A., Wilkinson, G., Hedgus, L. S., Eds.;
Elsevier: Oxford, 1995; p 39. (b) Normant, J. F.; Alexakis, A. Synthesis
1981, 841−870. (c) Vasil’ev, A. V. Russ. J. Org. Chem. 2009, 45, 1−17.
(34) Carlin, R. L.; Chirico, R. D.; Sinn, E.; Mennenga, G.; de Jongh,
L. J. Inorg. Chem. 1982, 21, 2218−2222.
(35) Hoe, W. M.; Cohen, A.; Handy, N. C. Chem. Phys. Lett. 2001,
341, 319−328.
(d) Den
2366−2447.
́ ̀ ́
es, F.; Perez-Luna, A.; Chemla, F. Chem. Rev. 2010, 110,
(36) Perdew, J. P.; Burke, K.; Ernzerhof, M. Phys. Rev. Lett. 1996, 77,
3865−3868.
(15) (a) Banks, R. L.; Bailey, G. C. Ind. Eng. Chem. Prod. Res. Dev.
1964, 3, 170−173. (b) Grubbs, R. H.; Chang, S. Tetrahedron 1998, 54,
4413−4450. (c) Schrock, R. R.; Murdzek, J. S.; Bazan, G. C.; Robbins,
J.; DiMare, M.; O’Regan, M. J. Am. Chem. Soc. 1990, 112, 3875−3886.
(d) Schwab, P.; Grubbs, R. H.; Ziller, J. W. J. Am. Chem. Soc. 1996,
118, 100−110.
(37) Swart, M.; Groenhof, A. R.; Ehlers, A. W.; Lammertsma, K. J.
Phys. Chem. A 2004, 108, 5479−5483.
(38) Friour, G.; Cahiez, G.; Normant, J. F. Synthesis 1985, 1, 50−54.
(39) Harvey, J. N.; Aschi, M.; Schwarz, H.; Koch, W. Theor. Chem.
Acc. 1998, 99, 95−99.
(16) (a) Mizoroki, T.; Mori, K.; Osaki, A. Bull. Chem. Soc. Jpn. 1971,
44, 581−581. (b) Heck, R. F.; Nolley, J. P. J. Org. Chem. 1972, 37,
2320−2322. (c) Cabri, W.; Candiani, I. Acc. Chem. Res. 1995, 28, 2−7.
(d) Beletskaya, I. P.; Cheprakov, A. V. Chem. Rev. 2000, 100, 3009−
3066.
(17) Denmark, S. E.; Butler, C. R. Chem. Commun. 2009, 20−33.
(18) (a) Tamao, K.; Sumitani, K.; Kumada, M. J. Am. Chem. Soc.
1972, 94, 4374−4376. (b) Shimasaki, T.; Konno, Y.; Tobisu, M.;
Chatani, N. Org. Lett. 2009, 11, 4890−4892. (c) Gauthier, D.;
Beckendorf, S.; Gøgsig, T. M.; Lindhardt, A. T.; Skrydstrup, T. J. Org.
Chem. 2009, 74, 3536−3539.
(19) (a) Hallberg, A.; Westerlund, C. Chem. Lett. 1982, 1993−1994.
(b) Shirakawa, E.; Yamasaki, K.; Hiyama, T. Synthesis 1998, 1544−
1549. (c) Denmark, S. E.; Choi, J. Y. J. Am. Chem. Soc. 1999, 121,
5821−5822.
(20) Yu, J. Y.; Kuwano, R. Angew. Chem., Int. Ed. 2009, 48, 7217−
7220.
́
(40) Amatore, C.; Carre, E.; Jutand, A.; Tanaka, H.; Quinghua, R.;
Torii, S. Chem.Eur. J. 1996, 2, 957−966.
(41) Nakao, Y.; Imanaka, H.; Sahoo, A. K.; Yada, A.; Hiyama, T. J.
Am. Chem. Soc. 2005, 127, 6952−6953.
(42) Selvakumar, K.; Zapf, A.; Beller, M. Org. Lett. 2002, 4, 3031−
3033.
(43) Wang, Z.; Wnuk, S. F. J. Org. Chem. 2005, 70, 3281−3284.
(44) Siamaki, A. R.; El Rahman, A.; Khder, S.; Abdelsayed, V.; El-
Shall, M. S.; Gupton, B. F. J. Catal. 2011, 279, 1−11.
(45) Arvela, R. K.; Leadbeater, N. E.; Sangi, M. S.; Williams, V. A.;
Granados, P.; Singer, R. D. J. Org. Chem. 2005, 70, 161−168.
(46) Solodenko, W.; Mennecke, K.; Vogt, C.; Gruhl, S.; Kirschning,
A. Synthesis 2006, 1873−1881.
(47) Luo, F.; Pan, C.; Wang, W.; Ye, Z.; Cheng, J. Tetrahedron 2010,
66, 1399−1403.
(48) Cella, R.; Stefani, H. A Tetrahedron 2006, 62, 5656−5662.
(49) Srinivas, P.; Srinivas, K.; Likhar, P. R.; Sridhar, B.; Mohan, K. V.;
Bhargava, S.; Kantam, M. L. J. Organomet. Chem. 2011, 206, 795−801.
(50) Nakao, Y.; Imanaka, H.; Chen, J.; Yada, A.; Hiyama, T. J.
Organomet. Chem. 2007, 692, 585−603.
(21) (a) Dohle, W.; Kopp, F.; Cahiez, G.; Knochel, P. Synlett 2001,
1901−1904. (b) Scheiper, B.; Bonnekessel, M.; Krause, H.; Furstner,
̈
A. J. Org. Chem. 2004, 69, 3943−3949. (c) Czaplik, W. M.; Mayer, M.;
Jacobi von Wangelin, A. ChemCatChem 2011, 3, 135−138.
(22) Cahiez, G.; Gager, O.; Lecomte, F. Org. Lett. 2008, 10, 5255−
5256.
(23) (a) Cahiez, G.; Avedissian, H. Tetrahedron Lett. 1998, 39, 6159−
6162. (b) Struzinski, T. H.; von Gohren, L. R.; Roy Mc Arthur, A. H.
Transition Met. Chem. 2009, 34, 637−640.
(24) (a) Gosmini, C.; Begouin, J. M.; Moncomble, A. Chem.
Commun. 2008, 3221−3233. (b) Gosmini, C.; Moncomble, A. Isr. J.
Chem. 2010, 50, 568−576.
(25) (a) Fillon, H.; Gosmini, C.; Perichon, J. J. Am. Chem. Soc. 2003,
125, 3867−3870. (b) Kazmierski, I.; Gosmini, C.; Paris, J. M.;
Perichon, J. Tetrahedron Lett. 2003, 44, 6417−6420. (c) Gosmini, C.;
Amatore, M.; Claudel, S.; Perichon, J. Synlett 2005, 2171−2174.
(d) Kazmierski, I.; Gosmini, C.; Paris, J. M.; Perichon, J. Synlett 2006,
881−884. (e) Gosmini, C.; Perichon, J. Org. Biomol. Chem. 2005, 3,
216−217. (f) Claudel, S.; Gosmini, C. Chem. Commun. 2007, 3667−
3669.
(26) (a) Gomes, P.; Gosmini, C.; Perichon, J. Org. Lett. 2003, 5,
1043−1045. (b) Amatore, M.; Gosmini, C.; Perichon, J. J. Org. Chem.
2006, 71, 6130−6134. (c) Amatore, M.; Gosmini, C. Chem. Commun.
5062
dx.doi.org/10.1021/jo3005149 | J. Org. Chem. 2012, 77, 5056−5062