Room-temperature, ligand- and base-free heck reactions of aryl diazonium salts at low palladium loading: Sustainable preparation of substituted stilbene derivatives

Article abstract of DOI:10.1002/chem.200903050

The Pd(OAc)₂-catalyzed Heck reaction of aryl diazonium salts with 2-arylacrylates led to cis-stilbenes with good to excellent stereoselectivity. The environmentally friendly protocol developed in this work features low palladium loading in technical-grade methanol at room temperature under base-, additive-, and ligand-free condi-tions. The same protocol applied to simple Heck coupling of aryl diazonium salts with methyl acrylate allows as-tonishingly low palladium loading, down to 0.005 mol %. The stereoselectivity experimentally observed for the synthesis of cis-stilbenes has been rationalized by DFT calculations. Moreover, the role of methanol in promoting the reaction has been clarified by a computational study.

Full text of DOI:10.1002/chem.200903050

FULL PAPER
DOI: 10.1002/chem.200903050
Room-Temperature, Ligand- and Base-Free Heck Reactions of Aryl
Diazonium Salts at Low Palladium Loading: Sustainable Preparation of
Substituted Stilbene Derivatives
FranÅois-Xavier Felpin,*[a] Karinne Miqueu,[b] Jean-Marc Sotiropoulos,*[b]
Eric Fouquet,[a] Oier Ibarguren,[a] and Julia Laudien[a]
Abstract: The Pd
(OAc)2-catalyzed
tions. The same protocol applied to
simple Heck coupling of aryl diazoni-
um salts with methyl acrylate allows as-
tonishingly low palladium loading,
down to 0.005 mol%. The stereoselec-
tivity experimentally observed for the
synthesis of cis-stilbenes has been ra-
tionalized by DFT calculations. More-
over, the role of methanol in promot-
ing the reaction has been clarified by a
computational study.
Heck reaction of aryl diazonium salts
with 2-arylacrylates led to cis-stilbenes
with good to excellent stereoselectivity.
The environmentally friendly protocol
developed in this work features low
palladium loading in technical-grade
methanol at room temperature under
base-, additive-, and ligand-free condi-
Keywords: diazo compounds · den-
sity functional calculations · Heck
reaction · palladium · sustainable
chemistry
Introduction
under mild conditions (25–708C), sometimes under ligand-
free and even base-free conditions.[5]
The Mizoroki–Heck reaction, arguably one of the most im-
portant methods for the creation of carbon–carbon bonds,
allows the coupling of aryl or vinyl halides with olefins.[1]
Since its discovery in the early 1970s,[2] an impressive
amount of work has been devoted to its development that
culminated in industrial applications.[3]
A variant of this coupling, involving the use of aryl diazo-
nium salts as aryl halide surrogates and known as the Mat-
suda–Heck reaction,[4] has been much less explored in spite
of several advantages including energy, cost, and waste ben-
efits. Indeed, the high reactivity of diazonium salts, which
can be classified as “super-electrophiles” allows coupling
We recently reported a novel approach for the prepara-
tion of 3-benzyl-2-oxindoles using a tandem Heck–reduc-
tion–cyclization (HRC) sequence catalyzed with a Pd/C cat-
alyst generated in situ[6] under ligand-, base-, and additive-
free conditions at only 408C. It features a number of advan-
tages to the organic chemist: in particular, the reduced
number of operations results in significant atom-economy
and waste-generation benefits. As a key step, the HRC pro-
cess[7] required coupling of aryl diazonium salts with 2-aryla-
crylates, furnishing functionalized stilbenes. At that time we
were not concerned with the stereoselectivity of the reac-
tion, since the newly created double bond was further re-
duced during the tandem process. Although diazonium salts
have been coupled with a variety of olefins including acryl-
ates, styrenes,[8] heterocycles,[9] and others[10] we were sur-
prised to find that the use of 2-arylacrylates has been largely
ignored even under classical Heck conditions.[11]
Here we present our results on the palladium-catalyzed
coupling of aryl diazonium salts with acrylates with a special
emphasis on 2-arylacrylates. Experimental conditions were
carefully optimized in order to decrease the palladium load-
ing and minimize waste and energy costs according to a sus-
tainable approach.[12] Moreover, theoretical calculations
were conducted to better understand the high stereoselectiv-
ity observed for the formation of cis-stilbenes.[13,14]
[a] Dr. F.-X. Felpin, Prof. E. Fouquet, O. Ibarguren, J. Laudien
Universitꢀ de Bordeaux, CNRS-UMR 5255
Institut des Sciences Molꢀculaires (ISM)
351, Cours de la Libꢀration, Talence, 33405 (France)
E-mail: fx.felpin@ism.u-bordeaux1.fr
[b] Dr. K. Miqueu, Dr. J.-M. Sotiropoulos
Universitꢀ de Pau et des Pays de l’Adour
UMR-CNRS 5254, IPREM
2, Avenue du Prꢀsident Angot
64053 Pau cedex 09 (France)
E-mail: jean-marc.sotiro@univ-pau.fr
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.200903050.
Chem. Eur. J. 2010, 16, 5191 – 5204
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Results and Discussion
decrease of the palladium loading to 0.10 mol% (Table1,
entry 6) and even 0.05 mol% (Table1, entry 7) resulted in
slightly lower but still remarkable yields (88–89%) due to
incomplete conversion (ca. 91–92%). Importantly, we con-
sistently obtained (E)-7a (corresponding to a cis-stilbene) as
During our previous studies on the Heck reactions of diazo-
nium salts with olefins including acrylate and styrene deriva-
tives,[15] we consistently observed perfect control of the
double-bond geometry in favor of the E isomers (Scheme 1,
Eqs. (1) and (2)). When we began this study we were unable
to predict the stereoselectivity of Heck arylation for the syn-
thesis of compounds D (Scheme 1, Eq. (3)).
1
the sole observable isomer in the H NMR spectrum of the
crude product. This unanticipated result opens the way for
stereoselective preparation of stilbene derivatives under
mild conditions (vide infra).
Solvent screening revealed
that methanol is the best sol-
vent for this kind of coupling.
Other solvents tested, including
CH3CN, PhCN, THF, dioxane,
and CH3COOH, proved to in-
hibit completely the reaction
(Table1, entries 8–12). In order
to understand the crucial role
of the solvent, we performed
DFT calculations. We compared
the coordination energy of
PhPd+ with both the solvent
(e.g., MeOH, CH3CN, and
THF) and methyl 2-(2-nitro-
phenyl)acrylate (6a).[15] Indeed,
the solvent should stabilize the
Scheme 1. Heck reactions with aryl diazonium salts.
PhPd+ complex enough by co-
ordination but not too much in
Optimization: Initially, coupling was optimized on a model
reaction involving methyl 2-(2-nitrophenyl)acrylate (6a) and
order to allow reaction with acrylate 6a. Theoretical results
are coherent with the experimental data, since formation of
the PhPd+–acrylate complex is exoergic with MeOH, iso-
4-(methoxycarbonyl)benzenediazonium
(1a) as coupling partners (Table 1). We arbitrarily started
with Pd(OAc)2 as catalyst. With a loading of 1 mol% of pal-
tetrafluoroborate
Table 1. Optimization studies for substrates 1a and 6a: variation of pal-
ladium source and solvent.
ACHTUNGTRENNUNG
ladium at 408C in technical-grade methanol, the reaction
evolved rapidly to give a high yield of the coupled product
7a (Table 1, entry 1). Although not presented here, the
effect of concentration on the reaction outcome was also
evaluated. We found that a concentration of 0.2m is the best
compromise in terms of yield and ease of stirring with
highly crystalline diazonium salts. Indeed, more diluted con-
ditions (0.1m) increased the reaction time and diminished
the yield (<90%), while concentrated solutions (0.5m) were
problematic for magnetic stirring (diazonium salts are highly
crystalline) and would require mechanical stirring.
At 408C the palladium loading could be reduced to
0.50 mol% with consistent activity (Table1, entry 2), but a
further decrease to 0.25 mol% gave incomplete conversion
(Table1, entry 3). Surprisingly, when the temperature was
raised to 608C, the reaction suddenly stopped after 30 min
with formation of palladium black and conversion was in-
complete (Table1, entry 4). We explained that result in
terms of rapid aggregation into large colloids of unstable
palladium(0) nanoparticles under ligand-free conditions.
This assumption was confirmed by the observation that
under milder conditions (258C) a high yield of 7a was ob-
tained with only 0.25 mol% palladium and no observable
formation of palladium black (Table1, entry 5). A further
Entry Pd source
Loading Solvent
[mol%]
T
t
Yield
[%][b]
G
[8C] [h]
1
2
3
4
5
6
7
8
Pd
Pd
Pd
Pd
Pd
Pd
Pd
Pd
Pd
Pd
Pd
Pd
N
1
0.5
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
CH3CN
PhCN
THF
dioxane
CH3COOH 25
MeOH
MeOH
MeOH
MeOH
MeOH
40
40
40
60
25
25
25
25
25
25
25
0.5 95
0.5 98
5
0.25
0.25
0.25
0.10
0.05
0.25
0.25
0.25
0.25
0.25
0.25
0.25
(84)
(63)
98
88
89
0
0
0
0
0
(5)
0
0
85
0
5
12
12
12
12
12
12
12
12
12
12
12
12
12
9
10
11
12
13
14
15
16
17
A
G
25
25
25
25
25
A
[d]
Pd
Pd
0.25
0.10
[a] Arylacrylate 6a (1 mmol) and aryl diazonium salt 1a (1.2 mmol) were
mixed in MeOH (5 mL) with Pd(OAc)2 and stirred at 258C for 12 h.
[b] Yield of isolated product. Conversion in parentheses. [c] dba=trans,-
trans-dibenzylideneacetone. [d] TFA=trifluoroacetate.
AHCTUNGTRENNUNG
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Heck Reactions of Aryl Diazonium Salts
FULL PAPER
energetic with THF, and endoergic with CH3CN,[17] that is,
PhPd+–MeOH can easily dissociate in favor of formation of
the PhPd+–acrylate complex. Solvents having considerable
coordination energy with PhPd+ such as CH3CN stabilize
too much PhPd+ and inhibit the reaction. On the other
hand, we also found that other sources of palladium were
not as effective as PdACHTNUGTRNEUNG(OAc)2 under the developed reaction
conditions (Table1, entries 13–17).
We further studied the influence of various additives for
their ability to stabilize generated palladium nanoparticles
(Table 2). Strong inhibition of coupling was observed when
Table 2. Optimization studies for substrates 1a and 6a: base and ligand
variations.[a]
Scheme 2. Ligands screened in the optimization studies. Fu=Furyl.
effect of the base itself (Table 2, entries 1 and 2) and the
phosphine. Indeed, it has been reported that phosphines and
phosphites give rise to de-diazonization pathway through
formation of aryl free radicals.[20]
In summary: Heck type reactions with diazonium salts are
best performed, in the majority of cases, at room tempera-
ture, under base-, ligand- and additive-free conditions in
methanol.
Entry
Loading
[mol%]
Base
Additive
Ligand
Yield
[%][b]
ACHTUNGTRENNUNG
1
2
3
4
5
6
7
8
0.25
0.25
0.25
0.25
0.25
0.25
0.25
0.25
0.25
0.25
0.25
0.10
0.25
0.10
0.25
0.25
0.25
0.25
CaCO3
NaOAc
–
–
–
–
CaCO3
–
CaCO3
–
–
–
CaCO3
–
–
CaCO3
–
CaCO3
–
–
–
–
–
–
(50)
0
98
88
0
(50)
(30)
83
(5)
(5)
91
81
(50)
80
PEG-400
PEG-400
TBAB
–
–
–
–
–
-
–
–
–
–
–
–
–
–
L1
L1
L2
L2
L3
L4
L4
L4
L5
L6
L6
L7
L7
Scope: Substituted 2-arylacrylates 6a–6k employed in this
study were easily accessed by methylenation of the corre-
sponding methyl phenylacetates (Table 3). These compounds
proved to be stable for months when stored in the freezer
(ꢀ208C), except compound 6i, for which we detected a ten-
dency to polymerization.
Having successfully optimized the coupling on a model re-
action, we next explored its scope with various coupling
partners (Table 4). Initially, we selected 2-arylacrylates
9
10
11
12
13
14
15
16
17
18
0
0
(75)
(5)
[a] 2-Acrylacrylate 6a (1 mmol) and aryl diazonium salt 1a (1.2 mmol)
were mixed in MeOH (5 mL) with Pd(OAc)2 and stirred at 258C for
AHCTUNGTRENNUNG
Table 3. Preparation of 2-arylacrylates.
12 h. [b] Yield of isolated product. Conversion in parentheses.
a base was used to trap the HBF4 liberated by the diazoni-
um salt (Table 2, entries 1 and 2). This observation was in
sharp contrast with usual Heck reactions, for which a base is
mandatory. The use of stabilizing agents for nanosized palla-
dium colloids gave contrasting results.[18] While the use of
tetrabutylammonium bromide (TBAB, 1 equiv) clearly pre-
vented any catalytic activity (Table 2, entry 5), PEG-400
(5% w/w) seemed to act as a spectator on the reaction out-
come (Table 2, entries 3 and 4).
Lastly, we screened a variety of ligands L1–L7 (Scheme 2)
including ferrocenyl phosphines[19] and biphenyl phosphines,
with or without the presence of CaCO3 as base. We ob-
served that ligands were at the best only spectators of the
reaction outcome but more frequently detrimental for the
success of the coupling. We believe that without a base, the
phosphine ligands would be rapidly protonated with genera-
tion of HBF4, resulting in its inability to stabilize palladium
species. In the presence of a base, we consistently observed
decreased activity, which could be attributed to the joint
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F.-X. Felpin, J.-M. Sotiropoulos et al.
Table 4. Preparation of variously substituted stilbenes by Heck-type coupling.[a]
Entry
1
Diazonium salt
Olefin
Product
Pd
(OAc)2 [mol%]
E/Z
Yield [%][b]
98
0.25
0.25
>98:2
2
3
>98:2
>98:2
99
52
0.5
4
5
0.25
0.1
>98:2
>98:2
83
93
6
7
0.5
0.5
>98:2
>98:2
98
81
8
9
0.5
0.5
>98:2
>98:2
92
93
10
11
0.5
0.5
>98:2
>98:2
92
95
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Heck Reactions of Aryl Diazonium Salts
Table 4. (Continued)
FULL PAPER
Entry
Diazonium salt
Olefin
Product
Pd
(OAc)2 [mol%]
E/Z
Yield [%][b]
86
12
0.5
0.5
80:20
13
14
80:20
85:15
81
88
0.5
15
16
17
0.9
>98:2
95:5
73
97
89
0.5
0.25
97:3
18
0.5
85:15
91
19
20
0.5
1.5
96:4
92
74
86:14
[a] 2-Acrylacrylate 6a (1 mmol) and aryl diazonium salt 1a (1.2 mmol) were mixed in MeOH (5 mL) with PdACHTNURTGEN(UNG OAc)2 and stirred at 258C for 12 h.
[b] Yield of isolated product.
having a nitro group on the aromatic ring at C2, since they
are valuable synthetic intermediates for the preparation of
oxindoles and related heterocycles.[6] As anticipated, the
coupling proceeded at low catalyst loading (0.1–0.5 mol%)
under mild conditions (258C) to furnish cis-stilbenes with
perfect control of the double-bond geometry (Table 4, en-
tries 1–10). Interestingly, the high stereoselectivity observed
does not seem to be related to any stereoelectronic effect
on the acrylate or the diazonium salt. Moreover, even highly
congested stilbenes such as 7c were isolated exclusively in
their E form; the modest yield in this case (Table 4, entry 3)
is attributed to the low reactivity of mesityl diazonium salt
1c leading to incomplete conversion. The E geometry of cis-
stilbenes prepared in this study was assigned by means of
1
Figure 1. X-ray crystal structure of 7c.
the H NMR shift of the olefinic proton at ~8 ppm (vs. ca.
7 ppm for the Z isomer). Moreover, this assignment was
confirmed by X-ray analysis of 7c (Figure 1).
To extend the scope of this method, we studied a variety
of 2-arylacrylates that do not bear a nitro group on the aro-
Chem. Eur. J. 2010, 16, 5191 – 5204
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F.-X. Felpin, J.-M. Sotiropoulos et al.
matic ring at C2. We were surprised to find that 2-arylacry-
lates 6e, 6i, and 6k led to a less selective reaction giving an
isomeric mixture of stilbenes (E/Zꢁ80/20) whatever the po-
sition of the substituents on the diazonium salt counterpart
(Table 4, entries 12–14, 18, 20). On the other hand, 2-chloro-,
2-cyano-, 2-methyl-, and 2,5-dimethoxy-2-phenylacrylates
gave cis-stilbenes in high isomeric purity (Table 4, en-
tries 15–17, 19), while reactions of 4-chloro-, and 3-methoxy-
2-phenylacrylates were less selective (Table 4, entries 18 and
20).
A careful analysis of all these couplings led to the estab-
lishment of an unanticipated rule. 2-Arylacrylates having at
least one substituent on the aromatic ring at C2 react with
diazonium salts under palladium catalysis to give almost ex-
clusively cis-stilbenes. Moreover, additional experiments, not
shown in Table 4, showed that the E/Z ratio was not depen-
dent on the palladium loading. These results could be ex-
tremely relevant for medicinal purposes, since compounds
7a–7t can all be viewed as synthetic analogues of the anti-
cancer natural products Combretastatin A1 and A4.[21]
Although the primary interest of this work focused on the
preparation of stilbenes, we also examined our conditions
for simple Heck-type reactions involving methyl acrylate (2)
and diazonium salts for comparison with substrates usually
screened in the literature (Table 5). We were surprised to
find that astonishingly low palladium loading could be used
(0.005–0.05% Pd) at room temperature in methanol. Such
low loadings have no literature precedent under base-,
ligand-, and additive-free conditions.
These results highlight the prodigious reactivity of diazo-
nium salts under palladium catalysis in methanol. This is all
the more relevant since most aryl diazonium tetrafluorobo-
rate salts are very stable in crystalline form (for several
years at ꢀ208C) and many are now commercially available.
Such an approach allows the development of a more envi-
ronmental friendly chemistry with significant atom economy
and waste reduction.
As previously demonstrated,[6] 2-(2-nitrophenyl)acrylates
are valuable synthetic intermediates for the preparation of
oxindoles (Table 6). Indeed, when treated with Pd/C under
H2 (1 atm) stilbenes 7a, 7c, and 7j were smoothly reduced
to give the corresponding oxindoles 9a–9c in good yield.
Table 6. Preparation of oxindoles from stilbenes.
Table 5. Coupling reactions at very low palladium loading.[a]
On the other hand, selective reduction of the nitro group
led to novel arylidenoxindoles with perfect control of the
double-bond geometry (Table 7). A brief survey of literature
precedents showed that these compounds are important syn-
thetic intermediates for the preparation of alkaloids and bio-
logically active compounds, such as those shown in
Scheme 3.[22] Moreover, recent papers testify to the growing
interest in arylidenoxindoles by medicinal chemists in oncol-
ogy.[23]
Entry
1
Product
Pd [mol%]
0.05
Yield [%][b]
98
2
3
4
0.05
0.01
0.005
98
96
93
Table 7. Preparation of arylidenoxindoles from stilbenes
5
6
0.05
0.05
81
93
[a] Methyl acrylate (1 mmol) and aryl diazonium salt (1.2 mmol) were
mixed in MeOH (5 mL) with Pd
[b] Yield of isolated product.
ACHTUNGERTN(NUNG OAc)2 and stirred at 258C for 12 h.
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Heck Reactions of Aryl Diazonium Salts
FULL PAPER
ing step of the reaction with the highest activation barrier.
Whatever the conformation of the phenyl ring bearing the
nitro group, the lower activation barrier is predicted for
structures in the transition state having the two phenyl
groups in a cis relation and leading to the corresponding cis-
stilbene (25.7 vs. 28.2 kcalmolꢀ1 in Figure 2 or 23.0 vs.
26.5 kcalmolꢀ1 in Figure 3). It is also noteworthy that all of
the cationic Pd complexes (minima or TSs) involved in
Figure 3 are far more stable than their analogues presented
in Figure 2, by 12–23 kcalmolꢀ1 (see Table 8 in the Support-
ing Information). This interesting observation can be ex-
Scheme 3. Representative oxindole-containing biologically active com-
pounds.
ꢀ
plained by the short Pd O distance and nO!4d(Pd) stabiliz-
ing interactions in the NBO calculations of conformations
reported in Figure 3 compared to conformations in which
the NO2 group has no influence (Figure 2). Therefore, the
high E selectivity (leading to the cis-stilbene) experimentally
observed with acrylates bearing a NO2 group at the ortho
Computational study: A computational study was undertak-
en on a model reaction to understand the stereoselectivity
observed. We assumed that the arylation of 6a with diazoni-
um salts proceeds in two important steps: 1) cis addition of
PhPd+ (A) to acrylate 6a and 2) rotation around the C1 C2
position can be rationalized by our calculations. The Pd O
ꢀ
ꢀ
bond followed by PdH syn b-elimination to give stilbenes
trans-7b or cis-7b (Scheme 4).
interaction also contributes to favor the discrimination of
2TStNO2 and 2TScNO2 (DG=3.5 kcalmolꢀ1, Figure 3 vs. DG=
2.5 kcalmolꢀ1, Figure 2).
Two energy profiles based on two conformations of inter-
mediate B were studied according to the position of the
NO2 substituent on the phenyl group [ortho (o, Figure 2) or
ortho’ (o’, Figure 3)]. The reaction starts with formation of
Since all of these results were obtained in the gas phase,
the role of methanol in the reaction outcome was also stud-
ied. We carried out PCM calculations considering methanol,
acetonitrile, tetrahydrofuran for the energy profile with the
NO2 group at the ortho’ position (Figure 2). PCM calcula-
tions show clearly that the presence of methanol better pro-
motes the two steps of the reaction (Steps 1 and 2) than ace-
tonitrile and THF (see Figure 6 in the Supporting Informa-
tion) and strongly diminishes the activation barrier of the
second step (by around half), which is the limiting step in
the gas-phase calculations. These data confirm that the sol-
vent helps the reaction to occur. As previously described,
the formation of the palladium acrylate complex is more or
less favored by the solvent.[1,17] Thus, both stabilization of
the palladium acrylate complex and the low activation
energy for H migration from carbon to palladium play a
role in the feasibility of the reaction. For methanol, these
two factors allow the reaction to occur easily.
ꢀ
p-PdPh complex 1NO2 (o and o’), in which the C1 C2 and
ꢀ
Pd C1/C2 bond lengths are respectively about 1.4 and
2.2 ꢂ.[24] We calculated that the first step (Step 1), corre-
sponding to cis addition of A to acrylate 6a has small activa-
tion barriers for 1TSNO2o and 1TSNO2oꢀ of 11.4 kcalmolꢀ1
(Figure 2) and 5.8 kcalmolꢀ1 (Figure 3) to give respectively
ꢀ
2NO2o and 2NO2o’. In complexes 2NO2o and 2NO2oꢀ the C2 C3
ꢀ
bond is definitively formed (C2 C3: 1.5 ꢂ vs. 2.7–3 ꢂ in
1NO2o’). The second step requires either a clockwise or an an-
ꢀ
ticlockwise rotation around the C1 C2 bond followed by
migration of a benzylic hydrogen atom (H or H1) on palladi-
um to give the pro-cis (2TScNO2) or the pro-trans (2TStNO2
)
complex.[25] Our calculations on the two energy profiles (Fig-
ures 2 and 3) unambiguously show that this process (i.e., ro-
ꢀ
tation around C1 C2 followed by H migration) is the limit-
Scheme 4. Mechanistic interpretation leading to cis- and trans-stilbenes
Chem. Eur. J. 2010, 16, 5191 – 5204
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F.-X. Felpin, J.-M. Sotiropoulos et al.
stilbene derivatives prepared in
this work has been evidenced
with the synthesis of oxindoles
and arylidenoxindoles. We be-
lieve that such a simple meth-
odology that fits in with many
principles
of
sustainable
chemistry[12] could be of interest
for synthetic and medicinal
chemists.
Experimental Section
General remarks: Chemical shifts
from proton and carbon NMR spectra
are reported in ppm relative to the
CDCl3 peak at 7.26 ppm (1H) or
77.0 ppm (13C). Infrared (IR) spectra
were recorded as neat samples on
NaCl plates or as KBr pellets. Yields
refer to isolated material determined
to be pure by NMR spectroscopy and
thin layer chromatography (TLC),
unless specified otherwise in the text.
Diazonium salts used in this study
were all known and prepared as de-
scribed in the literature.
General procedure for the methylena-
tion of esters (Table 3): HCHO
(28 mmol,
2.8 equiv),
Bu4NI
(0.2 mmol, 0.04 equiv), and K2CO3
(30 mmol, 3 equiv) were added to a
solution of ester (10 mmol, 1 equiv) in
toluene (13 mL) at room temperature.
The resulting mixture was stirred for
12 h at 508C. After cooling to room
temperature, water (10 mL) was added
and the aqueous phase was extracted
with toluene (2ꢃ20 mL). The collected
organic extracts were dried (MgSO4),
filtered, and concentrated under re-
duced pressure to give the correspond-
ing methylene ester, which was puri-
fied by flash chromatography.
Figure 2. Energy profile in the gas phase (DG in kcalmolꢀ1) of the reaction involving the NO2-substituted 2-
phenyl-2-nitroacrylate (NO2 group in ortho position). Step 1: cis addition of the acrylate on PhPd+; Step 2: ro-
Methyl 2-(2-nitrophenyl)acrylate (6a):
Purification by flash chromatography
(25% EtOAc/petroleum ether) gave
6a as a pale yellow oil (1.76 g, 85%
yield). IR (KBr): n˜ =1608, 1730, 2954,
c
ꢀ
tation around the C1 C2 bond, H migration from C2 to Pd leading to a PdH complex. 3 NO2o can be described
ꢀ
ꢀ
as a palladium complex involving a three-center interaction, consistent with the short Pd C1 and Pd C2 dis-
tances and NBO calculations (4dPd!2ppC2: 30.1 kcalmolꢀ1, 4dPd!2ppC1: 20.1 kcalmolꢀ1, and sC1C2!4dPd
:
6.6 kcalmolꢀ1).
3001 cmꢀ1
;
1H NMR
(CDCl3,
250 MHz): d=3.72 (s, 3H), 5.88 (s,
1H), 6.54 (s, 1H), 7.39 (dd, 1H, J=
1.6, 7.5 Hz), 7.53 (dt, 1H, J=1.6,
Conclusion
8.1 Hz), 7.65 (dt, 1H, J=1.4, 7.5 Hz), 8.12 ppm (dd, 1H, J=1.4, 8.1 Hz);
13C NMR (CDCl3, 75 MHz): d=52.3, 124.6, 127.5, 129.3, 132.1, 132.9,
133.6, 139.8, 147.8, 165.2 ppm; HRMS (electrospray) calcd for
C10H9NO4Na [M+Na]+: 230.0423, found: 230.0427.
We have described highly efficient Heck coupling of aryl di-
azonium salts with 2-arylacrylates leading to cis-stilbenes
with good to excellent E stereoselectivity. The coupling re-
ported herein features extremely mild conditions and a par-
ticularly simple and environmentally friendly experimental
protocol at low palladium loading. The high E stereoselec-
tivity observed has been explained and discussed on the
basis of DFT calculations. Lastly, the synthetic utility of the
Methyl 2-(4,5-dimethoxy-2-nitrophenyl)acrylate (6b): Purification by
flash chromatography (40% EtOAc/petroleum ether) gave 6b as
a
yellow solid (2.40 g, 90% yield). M.p. 1058C; IR (KBr): n˜ =1632, 1726,
1
2950, 3014, 3068 cmꢀ1; H NMR (CDCl3, 250 MHz): d=3.71 (s, 3H), 3.96
(s, 6H), 5.78 (d, 1H, J=1.0 Hz), 6.54 (d, 1H, J=1.0 Hz), 6.73 (s, 1H),
7.71 ppm (s, 1H); 13C NMR (CDCl3, 75 MHz): d=52.2, 56.4, 56.4, 107.7,
5198
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ꢁ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2010, 16, 5191 – 5204

Heck Reactions of Aryl Diazonium Salts
FULL PAPER
Methyl
2-(2-nitro-4-phenylphenyl)a-
crylate (6d): Purification by flash
chromatography (6% EtOAc/toluene)
gave 6d as a colorless oil (2.43 g, 86%
yield). IR (KBr): n˜ =1614, 1732, 2953,
3032, 3062 cmꢀ1
;
1H NMR (CDCl3,
300 MHz): d=3.75 (s, 3H), 5.93 (s,
1H), 6.57 (s, 1H), 7.43–7.53 (m, 4H),
7.62–7.64 (m, 2H), 7.85 (dd, 1H, J=
1.9, 7.9 Hz), 8.33 ppm (d, 1H, J=
1.9 Hz); 13C NMR (CDCl3, 75 MHz):
d=52.3, 128.9, 127.0, 127.5, 128.6,
129.1, 131.3, 131.8, 132.5, 138.0, 139.5,
142.7, 148.2, 165.3 ppm; HRMS (elec-
trospray) calcd for C16H13NO4Na
[M+Na]+: 306.0736, found: 306.0736.
Methyl 2-phenylacrylate (6e): Purifi-
cation by flash chromatography (5%
EtOAc/toluene) gave 6e as a colorless
oil (82% yield). IR (neat): n˜ =1614,
1722, 2953 cmꢀ1
;
1H NMR (CDCl3,
250 MHz): d=3.82 (s, 3H), 5.92 (d,
1H, J=1.2 Hz), 6.41 (d, 1H, J=
1.4 Hz), 7.35–7.50 ppm (m, 5H);
13C NMR (CDCl3, 75 MHz): d=52.1,
126.8, 128.0, 128.1, 128.2, 136.6, 141.3,
167.2 ppm.
Methyl
2-(2-cyanophenyl)acrylate
(6 f): Purification by flash chromatog-
raphy (25% EtOAc/petroleum ether)
gave 6 f as a white solid (1.47 g, 78%
yield). M.p. 578C; IR (KBr): n˜ =1625,
1725, 2228, 2954, 3002, 3069 cmꢀ1
;
1H NMR (CDCl3, 250 MHz): d=3.83
(s, 3H), 5.99 (s, 1H), 6.71 (s, 1H), 7.40
(d, 1H, J=7.7 Hz), 7.44 (app t, 1H,
J=7.5 Hz), 7.60 (app t, 1H, J=
7.7 Hz), 7.69 ppm (d, 1H, J=7.7 Hz);
13C NMR (CDCl3, 75 MHz): d=52.5,
112.4, 117.7, 128.4, 130.1, 131.4, 132.4,
132.8, 138.5, 140.7, 165.6 ppm; HRMS
(electrospray) calcd for C11H9NO2Na
[M+Na]+: 210.0525, found: 210.0528.
Methyl
2-(2-methylphenyl)acrylate
(6g): Purification by flash chromatog-
raphy (5% EtOAc/petroleum ether)
gave 6g as
56% yield);
a
colorless oil (986 mg,
1H NMR
(CDCl3,
200 MHz): d=2.23 (s, 3H), 3.78 (s,
3H), 5.73 (d, 1H, J=1.6 Hz), 6.54 (d,
1H, J=1.6 Hz), 7.13–7.33 ppm (m,
4H); 13C NMR (CDCl3, 50 MHz): d=
19.8, 52.2, 125.6, 128.1, 128.6, 129.4,
129.8, 136.1, 137.1, 141.7, 167.1 ppm;
HRMS (electrospray) calcd for
Figure 3. Energy profile in the gas phase (DG in kcalmolꢀ1) of the reaction involving the NO2-substituted 2-
phenyl-2-nitroacrylate (NO2 group in orthoꢄ position). Step 1: cis addition of the acrylate on PhPd+. Step 2: ro-
ꢀ
tation around the C1 C2 bond, H migration from C2 to Pd leading to a PdH complex. PCM values are given
in parentheses.
C11H12O2Na
found: 199.0735.
[M+Na]+:
199.0734,
113.4, 126.4, 127.5, 140.0, 140.3, 148.7, 153.2, 165.5 ppm; HRMS (electro-
Methyl 2-(2-chlorophenyl)acrylate (6h): Purification by flash chromatog-
raphy (10% EtOAc/petroleum ether) gave 6h as a colorless oil (1.08 g,
55% yield). IR (neat): n˜ =1626, 1728, 2845, 2952, 2998, 3002, 3027,
spray) calcd for C12H13NO6Na [M+Na]+: 290.0635, found: 290.0633.
Methyl 2-(4-methoxycarbonyl-2-nitrophenyl)acrylate (6c): Purification by
flash chromatography (20% EtOAc/petroleum ether) gave 6c as a white
solid (1.75 g, 66% yield). M.p. 558C; IR (KBr): n˜ =1617, 1731, 2956,
1
3060 cmꢀ1; H NMR (CDCl3, 300 MHz): d=3.79 (s, 3H), 5.80 (d, 1H, J=
1.5 Hz), 6.54 (d, 1H, J=1.1 Hz), 7.26–7.32 (m, 3H), 7.39–7.42 ppm (m,
1H); 13C NMR (CDCl3, 75 MHz): d=52.3, 126.7, 129.2, 129.3, 129.5,
130.8, 133.3, 136.5, 140.1, 166.4 ppm; HRMS (electrospray) calcd for
C10H10O2Cl [M+H]+: 197.0369, found: 197.0360.
3004, 3092 cmꢀ1 1H NMR (CDCl3, 300 MHz): d=3.71 (s, 3H), 3.97 (s,
;
3H), 5.93 (s, 1H), 6.59 (s, 1H), 7.48 (d, 1H, J=7.9 Hz), 8.27 (dd, 1H, J=
1.5, 7.9 Hz), 8.71 ppm (d, 1H, J=1.5 Hz); 13C NMR (CDCl3, 75 MHz):
d=52.3, 52.8, 125.6, 128.4, 131.5, 132.4, 134.1, 136.8, 139.0, 147.9, 164.6,
164.7 ppm; HRMS (electrospray) calcd for C12H11NO6Na [M+Na]+:
288.0478, found: 288.0476.
Methyl 2-(4-chlorophenyl)acrylate (6i): Purification by flash chromatog-
raphy (10% EtOAc/petroleum ether) gave 6i as a colorless oil (1.28 g,
65% yield). IR (neat): n˜ =1615, 1724, 2845, 2953, 2999, 3032 cmꢀ1
;
Chem. Eur. J. 2010, 16, 5191 – 5204
ꢁ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
5199

F.-X. Felpin, J.-M. Sotiropoulos et al.
1H NMR (CDCl3, 300 MHz): d=3.82 (s, 3H), 5.90 (s, 1H), 6.39 (s, 1H),
7.31–7.38 ppm (m, 4H); 13C NMR (CDCl3, 75 MHz): d=52.3, 127.3,
128.3, 129.6, 134.2, 135.1, 140.1, 166.8 ppm; HRMS (electrospray) calcd
for C10H9O2NaCl [M+Na]+: 219.0183, found: 219.0182.
Methyl (2E)-2-(2-nitrophenyl)-3-(4-nitrophenyl)acrylate (7e): The crude
product was purified by flash chromatography (25% EtOAc/petroleum
ether) to give 7e as a white solid (305 mg, 93% yield). M.p. 1188C; IR
1
(KBr): n˜ =1520, 1711, 2955 cmꢀ1; H NMR (CDCl3, 300 MHz): d=3.77 (s,
3H), 7.11 (dd, 1H, J=1.9, 7.1 Hz), 7.18 (d, 2H, J=8.7 Hz), 7.52–7.62 (m,
2H), 7.96 (s, 1H), 8.03 (d, 1H, J=9.0 Hz), 8.26 ppm (dd, 1H, J=1.9,
7.9 Hz); 13C NMR (CDCl3, 75 MHz): d=52.8, 123.6, 125.2, 129.9, 130.6,
130.8, 132.3, 133.8, 134.1, 137.1, 140.5, 147.5, 148.7, 165.5 ppm; HRMS
(electrospray) calcd for C16H12N2O6Na [M+Na]+: 351.0587, found:
351.0580.
Methyl 2-(2,5-dimethoxyphenyl)acrylate (6j): Purification by flash chro-
matography (20% EtOAc/petroleum ether) gave 6j as a white solid
(1.69 g, 76% yield). M.p. 528C; IR (KBr): n˜ =1626, 1715, 2835, 2956,
3005 cmꢀ1 1H NMR (CDCl3, 300 MHz): d=3.74 (s, 3H), 3.76 (s, 3H),
;
3.78 (s, 3H), 5.75 (d, 1H, J=1.4 Hz), 6.28 (d, 1H, J=1.4 Hz), 6.78–
6.85 ppm (m, 3H); 13C NMR (CDCl3, 50 MHz): d=52.0, 55.7, 56.3, 111.9,
114.1, 116.0, 126.5, 127.8, 139.6, 151.1, 153.5, 167.7 ppm; HRMS (electro-
spray) calcd for C12H14O4Na [M+Na]+: 245.0784, found: 245.0784.
Methyl (2E)-2-(2-nitro-4,5-dimethoxyphenyl)-3-(4-N,N-diethylaminophe-
nyl)acrylate (7 f): The crude product was purified by flash chromatogra-
phy (30% EtOAc/1% Et3N/petroleum ether) to give 7 f as a yellow solid
(406 mg, 98% yield). M.p. 1698C; IR (KBr): n˜ =1521, 1588, 1702, 2942,
Methyl 2-(3-methoxyphenyl)acrylate (6k): Purification by flash chroma-
tography (10% EtOAc/petroleum ether) gave 6k as a yellow oil (768 mg,
2968 cmꢀ1 1H NMR (CDCl3, 300 MHz): d=1.12 (t, 6H, J=7.2 Hz), 3.31
;
40% yield). IR (neat): n˜ =1600, 1724, 2837, 2952, 3001 cmꢀ1 1H NMR
;
(q, 4H, J=7.2 Hz), 3.71 (s, 3H), 3.82 (s, 3H), 4.02 (s, 3H), 6.42 (d, 2H,
J=9.0 Hz), 6.70 (s, 1H), 6.85 (d, 2H, J=9.0 Hz), 7.76 (s, 1H), 7.83 ppm
(s, 1H); 13C NMR (CDCl3, 75 MHz): d=12.5, 44.3, 52.1, 56.3, 56.4, 107.9,
110.8, 113.8, 120.5, 123.2, 127.7, 132.6, 140.1, 141.0, 148.3, 148.5, 153.5,
167.5 ppm; HRMS (electrospray) calcd for C22H27N2O6 [M+H]+:
415.1863, found: 415.1871.
(CDCl3, 300 MHz): d=3.83 (s, 6H), 5.90 (s, 1H), 6.37 (s, 1H), 6.87–6.91
(m, 1H), 6.96–7.02 (m, 2H), 7.28 ppm (app t, 1H, J=7.9 Hz); 13C NMR
(CDCl3, 75 MHz): d=52.2, 55.2, 113.7, 114.0, 120.7, 127.0, 129.1, 138.0,
141.1, 159.2, 167.1 ppm; HRMS (electrospray) calcd for C11H12O3Na
[M+Na]+: 215.0678, found: 215.0678.
General procedure for the Heck cross-coupling reaction (Table 4): Acry-
late (1 mmol) and PdACHTUNGTRENNUNG(OAc)2 (0.1–1.5 mol%, see Table 4) were added to
a solution of diazonium salt (1.2 mmol) in MeOH (2.5 mL) at 258C. The
resulting mixture was stirred for 12 h at 258C and then concentrated
under reduced pressure. The crude product was purified by flash chroma-
tography to give the corresponding product.
Methyl (2E)-2-(2-nitro-4,5-dimethoxyphenyl)-3-(2-methylphenyl)acrylate
(7g): The crude product was purified by flash chromatography (20%
EtOAc/petroleum ether) to give 7g as a white solid (289 mg, 81% yield).
M.p. 508C; IR (KBr): n˜ =1521, 1718, 2840, 2951 cmꢀ1 1H NMR (CDCl3,
;
300 MHz): d=2.36 (s, 3H), 3.57 (s, 3H), 3.76 (s, 3H), 3.96 (s, 3H), 6.32
(s, 1H), 6.72 (d, 1H, J=7.9 Hz), 6.86–6.91 (m, 1H), 7.08–7.15 (m, 2H),
7.74 (s, 1H), 8.04 ppm (s, 1H); 13C NMR (CDCl3, 75 MHz): d=19.9, 52.4,
56.1, 56.3, 103.6, 114.1, 125.7, 126.2, 128.8, 129.1, 130.1, 132.0, 133.7,
137.2, 138.7, 141.4, 148.4, 152.9, 166.4 ppm; HRMS (electrospray) calcd
for C19H19NO6Na [M+Na]+: 380.1104, found: 380.1111.
Methyl
(2E)-2-(2-nitrophenyl)-3-(4-methoxycarbonylphenyl)acrylate
(7a): The crude product was purified by flash chromatography (30%
EtOAc/petroleum ether) to give 7a as a white solid (334 mg, 98% yield).
M.p. 808C; IR (KBr): n˜ =1633, 1717, 1733, 2846, 2904, 2953, 3001, 3033,
3068 cmꢀ1 1H NMR (CDCl3, 200 MHz): d=3.75 (s, 3H), 3.85 (s, 3H),
;
Methyl (2E)-2-(2-nitro-4-methoxycarbonylphenyl)-3-(4-isopropylpheny-
l)acrylate (7h): The crude product was purified by flash chromatography
(20% EtOAc/petroleum ether) to give 7h as a yellow oil (352 mg, 92%
7.06 (d, 2H, J=8.3 Hz), 7.11–7.15 (m, 1H), 7.46–7.59 (m, 2H), 7.82 (d,
2H, J=8.4 Hz), 7.94 (s, 1H), 8.19–8.27 ppm (m, 1H); 13C NMR (CDCl3,
50 MHz): d=52.2, 52.6, 125.0, 129.5, 129.5, 129.9, 130.3, 131.4, 132.1,
132.5, 133.9, 138.4, 138.7, 148.6, 165.9, 166.3 ppm; HRMS (electrospray)
calcd for C18H15NO6Na [M+Na]+: 364.0791, found: 364.0792.
yield). IR (neat): n˜ =1538, 1732, 2958 cmꢀ1 1H NMR (CDCl3, 300 MHz):
;
d=1.17 (d, 6H, J=7.1 Hz), 2.82 (quint, 1H, J=7.1 Hz), 3.73 (s, 3H), 3.99
(s, 3H), 6.92 (d, 2H, J=8.3 Hz), 7.04 (d, 2H, J=8.3 Hz), 7.33 (d, 1H, J=
7.9 Hz), 7.95 (s, 1H), 8.19 (d, 1H, J=8.6 Hz), 8.85 ppm (s, 1H);
13C NMR (CDCl3, 75 MHz): d=23.6, 33.9, 52.5, 52.8, 126.0, 126.7, 127.7,
130.5, 131.0, 131.3, 133.2, 134.2, 136.7, 141.0, 148.9, 151.1, 164.8,
166.0 ppm; HRMS (electrospray) calcd for C21H21NO6Na [M+Na]+:
406.1261, found: 406.1253.
Methyl
(2E)-2-(2-nitrophenyl)-3-(4-methoxycarbonylphenyl)acrylate
(7b): The crude product was purified by flash chromatography (20%
EtOAc/petroleum ether) to give 7b as a white solid (280 mg, 99% yield).
M.p. 99–1008C; IR (KBr): n˜ =1525, 1628, 1708, 2952, 3023, 3073 cmꢀ1
;
1H NMR (CDCl3, 300 MHz): d=3.75 (s, 3H), 7.00 (d, 2H, J=9.1 Hz),
7.14–7.22 (m, 4H), 7.50–7.56 (m, 2H), 7.94 (s, 1H), 8.19–8.25 ppm (m,
1H); 13C NMR (CDCl3, 75 MHz): d=52.4, 124.9, 128.4, 129.2, 129.3,
129.8, 130.2, 132.0, 132.7, 133.8, 133.9, 140.1, 148.8, 166.4 ppm; HRMS
(electrospray) calcd for C16H13NO4Na [M+Na]+: 306.0736, found:
306.0749.
Methyl (2E)-2-(2-nitro-4-methoxycarbonylphenyl)-3-(4-methoxybipheny-
l)acrylate (7i): The crude product was purified by flash chromatography
(20% EtOAc/petroleum ether) to give 7i as a yellow solid (416 mg, 93%
yield). M.p. 1488C; IR (KBr): n˜ =1533, 1601, 1610, 1717, 1729, 2842,
2955, 3012 cmꢀ1 1H NMR (CDCl3, 300 MHz): d=3.75 (s, 3H), 3.82 (s,
;
Methyl (2E)-2-(2-nitrophenyl)-3-(2,4,6-trimethylphenyl)acrylate (7c):
The crude product was purified by flash chromatography (10% EtOAc/
petroleum ether) to give 7c as a white solid (169 mg, 52% yield). M.p.
3H), 3.99 (s, 3H), 6.93 (d, 2H, J=8.6 Hz), 7.05 (d, 2H, J=8.3 Hz), 7.33–
7.39 (m, 3H), 7.46 (d, 2H, J=8.7 Hz), 8.00 (s, 1H), 8.19 (dd, 1H, J=1.5,
7.9 Hz), 8.87 ppm (d, 1H, J=1.5 Hz); 13C NMR (CDCl3, 75 MHz): d=
52.5, 52.8, 55.3, 114.3, 126.1, 126.6, 128.0, 128.4, 130.8, 131.3, 131.7, 132.1,
133.2, 134.2, 136.6, 140.7, 142.0, 148.9, 159.6, 164.7, 165.9 ppm; HRMS
(electrospray) calcd for C25H21NO7Na [M+Na]+: 470.1210, found:
470.1221.
1738C; IR (KBr): n˜ =1520, 1712, 2855, 2924, 2956 cmꢀ1
;
1H NMR
(CDCl3, 300 MHz): d=2.05 (s, 6H), 2.22 (s, 3H), 3.75 (s, 3H), 6.74 (s,
2H), 6.84 (dd, 1H, J=1.5, 7.5 Hz), 7.30 (dt, 1H, J=1.5, 7.5 Hz), 7.38 (dt,
1H, J=1.5, 7.5 Hz), 8.00 (s, 1H), 8.12 ppm (dd, 1H, J=1.5, 7.9 Hz);
13C NMR (CDCl3, 75 MHz): d=19.9, 20.9, 52.3, 124.7, 128.4, 128.8, 130.4,
131.4, 132.4, 132.7, 133.0, 135.8, 137.8, 140.8, 147.9, 165.9 ppm; HRMS
(electrospray) calcd for C19H19NO4Na [M+Na]+: 348.1206, found:
348.1215.
Methyl (2E)-2-(2-nitro-4-phenylphenyl)-3-phenylacrylate (7j): The crude
product was purified by flash chromatography (10% EtOAc/petroleum)
to give 7j as a cream-colored solid (330 mg, 92% yield). M.p. 1498C; IR
(KBr): n˜ =1527, 1703, 2951, 3030, 3067 cmꢀ1
;
1H NMR (CDCl3,
200 MHz): d=3.78 (s, 3H), 7.07–7.12 (m, 2H), 7.18–7.29 (m, 4H), 7.44–
7.56 (m, 3H), 7.66–7.79 (m, 3H), 7.99 (s, 1H), 8.48 ppm (d, 1H, J=
2.4 Hz); 13C NMR (CDCl3, 50 MHz): d=52.5, 123.2, 127.0, 128.4, 128.7,
129.1, 129.3, 129.5, 130.2, 130.5, 131.9, 133.1, 133.9, 137.9, 140.2, 142.3,
149.1, 166.4 ppm; HRMS (electrospray) calcd for C22H17NO4Na
[M+Na]+: 382.1049, found: 382.1047.
Methyl (2E)-2-(2-nitrophenyl)-3-(2-bromophenyl)acrylate (7d): The
crude product was purified by flash chromatography (15% EtOAc/petro-
leum ether) to give 7d as a white solid (300 mg, 83% yield). M.p. 1438C;
IR (KBr): n˜ =1527, 1709, 2956, 3064 cmꢀ1 1H NMR (CDCl3, 300 MHz):
;
d=3.77 (s, 3H), 6.39 (dd, 1H, J=1.1, 7.5 Hz), 6.95 (t, 1H, J=7.9 Hz),
7.01–7.09 (m, 2H), 7.38–7.48 (m, 2H), 7.56 (d, 1H, J=7.9 Hz), 8.05 (s,
1H), 8.16 ppm (dd, 1H, J=2.3, 6.8 Hz); 13C NMR (CDCl3, 75 MHz): d=
52.5, 124.6, 127.0, 129.1, 130.1, 130.8, 131.2, 132.6, 132.9, 133.6, 135.2,
139.5, 149.0, 165.6 ppm; HRMS (electrospray) calcd for C16H12NO4NaBr
[M+Na]+: 383.9841, found: 383.9848.
Methyl (2E)-2-(2-nitro-4-phenylphenyl)-3-(4-methoxycarbonylphenyl)a-
crylate (7k): The crude product was purified by flash chromatography
(20% EtOAc/petroleum ether then 70% CH2Cl2/petroleum ether) to
give 7k as a white solid (396 mg, 95% yield). M.p. 1698C; IR (KBr): n˜ =
5200
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ꢁ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2010, 16, 5191 – 5204

Heck Reactions of Aryl Diazonium Salts
FULL PAPER
1
1528, 1722, 2951, 2996, 3028, 3047 cmꢀ1; H NMR (CDCl3, 200 MHz): d=
(KBr): n˜ =1605, 1633, 1719, 2844, 2925, 2952, 3001 cmꢀ1 1H NMR
;
3.78 (s, 3H), 3.86 (s, 3H), 7.15 (d, 2H, J=7.9 Hz), 7.19 (d, 1H, J=
7.8 Hz), 7.42–7.54 (m, 3H), 7.65 (dd, 2H, J=1.7, 8.1 Hz), 7.74 (dd, 1H,
J=1.8, 7.9 Hz), 7.86 (d, 2H, J=8.4 Hz), 7.99 (s, 1H), 8.47 ppm (d, 1H,
J=1.8 Hz); 13C NMR (CDCl3, 50 MHz): d=52.2, 52.6, 123.2, 127.0, 128.7,
129.1, 129.6, 129.8, 130.0, 130.3, 131.8, 132.0, 133.0, 137.8, 138.5, 138.8,
142.7, 149.1, 166.0, 166.3 ppm; HRMS (electrospray) calcd for
C24H19NO6Na [M+Na]+: 440.1104, found: 440.1096.
(CDCl3, 300 MHz, major isomer): d=3.79 (s, 3H), 3.86 (s, 3H), 7.08 (d,
2H, J=8.3 Hz), 7.10 (dd, 1H, J=1.5, 7.8 Hz), 7.23 (app dt, 1H, J=1.1,
7.5 Hz), 7.33 (app dt, 1H, J=1.9, 7.5 Hz), 7.47 (dd, 1H, J=1.0, 7.9 Hz),
7.83 (d, 2H, J=8.7 Hz), 7.94 ppm (s, 1H); 13C NMR (CDCl3, 75 MHz,
major isomer): d=52.1, 52.6, 127.2, 129.5, 129.7, 129.7, 129.9, 130.3, 131.0,
132.1, 134.0, 134.7, 138.6, 140.3, 166.3, 167.0 ppm; HRMS (electrospray)
calcd for C18H16O4Cl [M+H]+: 331.0731, found: 331.0734.
Methyl (2E)-2-phenylphenyl-3-(4-methoxycarbonylphenyl)acrylate (7l):
The crude product was purified by flash chromatography (10% EtOAc/
petroleum ether) to give 7l as a white solid (255 mg, 86% yield) in the
form of two inseparable isomers (E/Z: 80/20). M.p. 978C; IR (KBr): n˜ =
Methyl
(2E)-2-(4-chlorophenyl)-3-(4-methoxycarbonylphenyl)acrylate
(7r): The crude product was purified by flash chromatography (10%
EtOAc/petroleum ether) to give 7r as a white solid (301 mg, 91% yield)
in the form of two inseparable isomers (E/Z: 85/15). M.p. 1048C; IR
1717, 2949, 3032 cmꢀ1; H NMR (CDCl3, 300 MHz): d=3.78 (s, 3Hꢃ0.2),
(KBr): n˜ =1608, 1623, 1724, 2842, 2947, 2993 cmꢀ1 1H NMR (CDCl3,
;
1
3.80 (s, 3Hꢃ0.8), 3.86 (s, 3Hꢃ0.8), 3.92 (s, 3Hꢃ0.2), 7.06 (s, 1Hꢃ0.2),
7.09 (d, 2Hꢃ0.8, J=8.3 Hz), 7.18–7.22 (m, 2Hꢃ0.8), 7.34–7.36 (m, 3Hꢃ
0.8), 7.34–7.37 (m, 3Hꢃ0.2), 7.43 (d, 2Hꢃ0.2, J=8.7 Hz), 7.46–7.79 (m,
2Hꢃ0.2), 7.81 (d, 2Hꢃ0.8, J=8.3 Hz), 7.86 (s, 1Hꢃ0.8), 8.03 ppm (d,
2Hꢃ0.2, J=8.3 Hz); 13C NMR (CDCl3, 50 MHz): d=52.1, 52.1, 52.3,
52.5, 126.5, 128.0, 128.1, 128.7, 128.8, 129.3, 129.6, 129.7, 130.0, 130.2,
130.3, 134.6, 135.2, 136.3, 136.8, 139.1, 140.2, 166.4, 166.6, 167.9,
169.6 ppm; HRMS (electrospray) calcd for C18H16O4Na [M+Na]+:
319.0940, found: 319.0940.
300 MHz): d=3.76 (s, 3Hꢃ0.15), 3.80 (s, 3Hꢃ0.85), 3.86 (s, 3Hꢃ0.85),
3.91 (s, 3Hꢃ0.15), 7.04 (s, 1Hꢃ0.15), 7.10 (d, 2Hꢃ0.85, J=8.7 Hz), 7.13
(d, 2Hꢃ0.85, J=8.3 Hz), 7.32 (d, 2Hꢃ1, J=8.3 Hz), 7.38 (d, 2Hꢃ0.15,
J=7.8 Hz), 7.40 (d, 2Hꢃ0.15, J=8.7 Hz), 7.84 (d, 2Hꢃ0.85, J=8.3 Hz),
7.86 (s, 1H), 8.02 ppm (d, 2Hꢃ0.85, J=8.3 Hz); 13C NMR (CDCl3,
75 MHz, E/Z mixture): d=52.2, 52.5, 52.6, 127.2, 127.9, 128.1, 129.0,
129.5, 129.8, 130.2, 130.9, 131.2, 133.4, 133.6, 134.2, 134.7, 134.9, 135.6,
138.8, 139.7, 139.9, 166.4, 167.5, 169.2 ppm; HRMS (electrospray) calcd
for C18H16O4Cl [M+H]+: 331.0731, found: 331.0732.
Methyl (2E)-2-phenylphenyl-3-(3-trifluoromethylphenyl)acrylate (7m):
The crude product was purified by flash chromatography (10% EtOAc/
petroleum ether) to give 7m as a colorless oil (233 mg, 76% yield) in the
form of two inseparable isomers (E/Z: 80/20). IR (neat): n˜ =1717, 2953,
Methyl (2E)-2-(2,5-dimethoxyphenyl)-3-(4-methoxycarbonylphenyl)acry-
late (7s): The crude product was purified by flash chromatography (20%
EtOAc/petroleum ether) to give 7s as a yellow solid (328 mg, 92% yield)
in the form of two inseparable isomers (E/Z: 96/04). M.p. 998C; IR
1
3026, 3060 cmꢀ1
;
1H NMR (CDCl3, 300 MHz): d=3.78 (s, 3Hꢃ0.2), 3.81
(KBr): n˜ =1617, 1709, 2839, 2951, 3079 cmꢀ1; H NMR (CDCl3, 300 MHz,
(s, 3Hꢃ0.8), 7.04 (s, 1Hꢃ0.2), 7.17–7.21 (m, 3Hꢃ0.8), 7.23–7.28 (m,
2Hꢃ0.8), 7.36–7.40 (m, 3Hꢃ0.8), 7.39–7.50 (m, 6Hꢃ0.2), 7.42–7.46 (m,
2Hꢃ0.8), 7.53–7.57 (m, 2Hꢃ0.2), 7.63 (s, 1Hꢃ0.2), 7.85 ppm (s, 1Hꢃ
0.8); HRMS (electrospray) calcd for C17H14O2F3 [M+H]+: 307.0940,
found: 307.0948.
major isomer): d=3.66 (s, 3H), 3.66 (s, 3H), 3.78 (s, 3H), 3.86 (s, 3H),
6.58 (s, 1H), 6.88 (app s, 2H), 7.15 (d, 2H, J=8.3 Hz), 7.81 (s, 1H),
7.83 ppm (d, 2H, J=8.1 Hz); 13C NMR (CDCl3, 75 MHz, major isomer):
d=52.1, 52.4, 55.6, 56.2, 112.4, 114.5, 116.2, 125.3, 129.3, 129.8, 131.5,
139.1, 139.3, 151.5, 153.6, 166.5, 167.9 ppm; HRMS (electrospray) calcd
for C20H20O6Na [M+Na]+: 379.1152, found: 379.1155.
Methyl (2E)-2-phenylphenyl-3-(2-bromophenyl)acrylate (7n): The crude
product was purified by flash chromatography (15% EtOAc/petroleum
ether) to give 7n as a white solid (317 mg, 88% yield). M.p. 1438C; IR
Methyl (2E)-2-(3-methoxyphenyl)-3-(4-methoxycarbonylphenyl)acrylate
(7t): The crude product was purified by flash chromatography (20%
EtOAc/petroleum ether) to give 7t as a colorless oil (261 mg, 80% yield)
in the form of two inseparable isomers (E/Z: 86/14). IR (neat): n˜ =1606,
(KBr): n˜ =1527, 1709, 2957, 3064 cmꢀ1 1H NMR (CDCl3, 300 MHz): d=
;
3.77 (s, 3H), 6.75 (d, 1H, J=7.5 Hz), 6.95 (t, 1H, J=7.9 Hz), 7.02–7.09
(m, 2H), 7.39–7.48 (m, 2H), 7.56 (d, 1H, J=7.9 Hz), 8.05 (s, 1H),
8.16 ppm (dd, 1H, J=2.3, 6.8 Hz); 13C NMR (CDCl3, 75 MHz): d=52.5,
124.6, 127.0, 129.1, 130.1, 130.8, 131.2, 132.6, 132.9, 133.6, 135.2, 139.5,
149.0, 165.6 ppm; HRMS (electrospray) calcd for C16H12NO4NaBr
[M+Na]+: 383.9841, found: 383.9815.
1716, 2839, 2952, 3001 cmꢀ1 1H NMR (CDCl3, 300 MHz, mixture iso-
;
mers): d=3.75 (s, 3Hꢃ0.86), 3.77 (s, 3Hꢃ0.14), 3.80 (s, 3Hꢃ0.86), 3.83
(s, 3Hꢃ0.14), 3.86 (s, 3Hꢃ0.86), 3.92 (s, 3Hꢃ0.14), 6.75 (s, 1Hꢃ0.86),
6.76 (d, 1Hꢃ0.86, J=10.6 Hz), 6.87–6.93 (m, 1Hꢃ0.86, 1Hꢃ0.14), 7.00–
7.09 (m, 3Hꢃ0.14), 7.05 (s, 1Hꢃ0.14), 7.11 (d, 2Hꢃ0.86, J=8.3 Hz), 7.28
(app t, 1Hꢃ0.86, J=7.8 Hz), 7.42 (d, 2Hꢃ0.14, J=8.3 Hz), 7.82 (d, 2Hꢃ
0.86, J=8.3 Hz), 7.83 (s, 1Hꢃ0.86), 8.02 ppm (d, 2Hꢃ0.14, J=8.4 Hz);
13C NMR (CDCl3, 75 MHz, mixture of isomers): d=52.1, 52.4, 52.5, 55.1,
55.3, 104.5, 112.1, 113.6, 114.2, 115.0, 119.0, 121.8, 128.0, 129.3, 129.8,
130.0, 130.3, 134.3, 136.5, 136.7, 137.7, 138.9, 139.1, 140.0, 159.7, 166.4,
167.8, 169.5 ppm; HRMS (electrospray) calcd for C19H18O5Na [M+Na]+:
349.1046, found: 349.1047.
Methyl
(2E)-2-(2-cyanophenyl)-3-(4-methoxycarbonylphenyl)acrylate
(7o): The crude product was purified by flash chromatography (20%
EtOAc/petroleum ether) to give 7o as a yellow oil (234 mg, 73% yield).
IR (neat): n˜ =1631, 1715, 2847, 2952, 2996 cmꢀ1 1H NMR (CDCl3,
;
250 MHz): d=3.82 (s, 3H), 3.86 (s, 3H), 7.03 (d, 2H, J=8.5 Hz), 7.30 (d,
1H, J=7.7 Hz), 7.48 (dt, 1H, J=1.4, 7.7 Hz), 7.59 (dt, 1H, J=1.4,
7.7 Hz), 7.71 (dd, 1H, J=1.4, 7.7 Hz), 7.83 (d, 2H, J=8.5 Hz), 8.07 ppm
(s, 1H); 13C NMR (CDCl3, 75 MHz): d=52.2, 52.7, 113.5, 117.2, 128.7,
129.5, 130.0, 130.7, 130.9, 132.9, 133.2, 138.0, 139.4, 142.2, 166.2 ppm;
HRMS (electrospray) calcd for C19H15NO4Na [M+Na]+: 344.0893,
found: 344.0898.
General procedure for Heck cross-coupling reaction with methyl acrylate
(Table 5): Acrylate (1 mmol) and PdACHTUNRGTNEUNG(OAc)2 (0.005–0.05 mol%, see
Table 5) were added to a solution of diazonium salt (1.2 mmol) in MeOH
(2.5 mL) at 258C. The resulting mixture was stirred for 12 h at 258C and
then concentrated under reduced pressure. The crude product was puri-
fied by flash chromatography to give the corresponding product.
Methyl
(2E)-2-(2-methylphenyl)-3-(4-methoxycarbonylphenyl)acrylate
(7p): The crude product was purified by flash chromatography (10%
EtOAc/petroleum ether) to give 7p as a white solid (301 mg, 97% yield)
in the form of two inseparable isomers (E/Z: 95/05). M.p. 638C; IR
(E)-Methyl 2-nitrocinnamate (8a): Purification by flash chromatography
(70% CH2Cl2/petroleum ether) gave 8a as a yellow solid (203 mg, 98%).
(KBr): n˜ =1721, 2924, 2953, 3006 cmꢀ1
;
1H NMR (CDCl3, 300 MHz,
M.p. 728C (Lit.[26] 71–728C); IR (KBr): n˜ =1637, 1719, 2953, 3024 cmꢀ1
;
major isomer): d=2.12 (s, 3H), 3.79 (s, 3H), 3.86 (s, 3H), 7.04 (d, 2H,
J=8.3 Hz), 7.04–7.07 (m, 1H), 7.18–7.33 (m, 3H), 7.81 (d, 2H, J=
8.3 Hz), 7.90 ppm (s, 1H); 13C NMR (CDCl3, 75 MHz, major isomer): d=
19.5, 52.1, 52.5, 126.4, 128.4, 129.2, 129.4, 130.0, 130.2, 130.4, 133.9, 135.0,
136.3, 139.0, 139.2, 166.4, 167.9 ppm; HRMS (electrospray) calcd for
C19H18O4 [M+H]+: 311.1277, found: 311.1276.
1H NMR (CDCl3, 250 MHz): d=3.80 (s, 3H), 6.34 (d, 1H, J=15.9 Hz),
7.49–7.68 (m, 4H), 8.01 (d, 1H, J=7.9 Hz), 8.08 ppm (d, 1H, J=
15.9 Hz); 13C NMR (CDCl3, 50 MHz): d=51.9, 122.7, 124.8, 129.0, 130.3,
130.4, 133.5, 140.0, 148.2, 166.1 ppm; MS (EI): m/z 207 [M], 176
[MꢀOCH3].
(E)-Methyl 4-bromoocinnamate (8b): Purification by flash chromatogra-
phy (20% AcOEt/petroleum ether) gave 8b as a white solid (235 mg,
98%). M.p. 888C [Lit.[27] 88–938C]; IR (KBr): n˜ =1643, 1711, 1959, 3033,
Methyl
(2E)-2-(2-chlorophenyl)-3-(4-methoxycarbonylphenyl)acrylate
(7q): The crude product was purified by flash chromatography (10%
EtOAc/petroleum ether) to give 7q as a white solid (294 mg, 89% yield)
in the form of two inseparable isomers (E/Z: 97/03). M.p. 918C; IR
1
3049 cmꢀ1; H NMR (CDCl3, 300 MHz): d=3.80 (s, 3H), 6.42 (d, 1H, J=
15.8 Hz), 7.38 (d, 2H, J=8.3 Hz), 7.51 (d, 1H, J=8.6 Hz), 7.62 ppm (d,
Chem. Eur. J. 2010, 16, 5191 – 5204
ꢁ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
5201

F.-X. Felpin, J.-M. Sotiropoulos et al.
1H, J=16.2 Hz); 13C NMR (CDCl3, 75 MHz): d=51.8, 118.5, 124.5,
129.4, 132.1, 133.3, 143.5, 167.1 ppm; MS (EI): m/z 240 [M, 79Br], 242 [M,
81Br], 161 [MꢀBr].
180.3 ppm; HRMS (electrospray) calcd for C23H16NO [M] 322.1226,
found: 322.1219.
General procedure for the preparation of arylidenoxindoles from acryl-
ates (Table 7): Fe (168 mg, 3 mmol) and NH4Cl (32.1 mg, 0.6 mmol) were
added to a solution of the corresponding acrylate (1 mmol) in EtOH
(8 mL) and H2O (2 mL). After being stirred for 4 h at 808C, the resulting
mixture was diluted with water (8 mL) and extracted with CH2Cl2 (3ꢃ).
The collected organic extracts were dried (MgSO4), filtered, and concen-
trated under reduced pressure.
(E)-Methyl 3-trifluoromethylcinnamate (8c): Purification by flash chro-
matography (10% AcOEt/petroleum ether) gave 8c as a white solid
(221 mg, 96%). M.p. 418C [Lit.[28] 36.58C]; IR (KBr): n˜ =1634, 1713,
1
2948, 2997, 3032 cmꢀ1; H NMR (CDCl3, 250 MHz): d=3.82 (s, 3H), 6.50
(d, 1H, J=16.2 Hz), 7.52 (app t, 1H, J=7.9 Hz), 7.62–7.76 (m, 3H),
7.71 ppm (d, 1H, J=16.2 Hz); MS (EI): m/z 230 [M], 161 [MꢀCF3].
(E)-3-(2-Methylbenzylidene)-5,6-dimethoxyoxindole
workup, 10a was obtained as a yellow solid (289 mg, 98%). M.p. 1528C;
IR (KBr): n˜ =1620, 1695, 2836, 2959, 3006, 3164 cmꢀ1 1H NMR (CDCl3,
(10a):
After
(E)-Methyl 4-methoxy-3-nitrocinnamate (8d): Purification by flash chro-
matography (10% AcOEt/petroleum ether) gave 8d as a yellow solid
(220 mg, 93%). M.p. 1288C [Lit.[29] 130–130.58C]; IR (KBr): n˜ =1639,
;
1702, 2952, 2983, 3062 cmꢀ1 1H NMR (CDCl3, 250 MHz): d=3.80 (s,
;
300 MHz): d=2.37 (s, 3H), 3.57 (s, 3H), 3.87 (s, 3H), 6.52 (s, 1H), 6.83
(s, 1H), 7.23–7.35 (m, 3H), 7.60 (d, 1H, J=7.5 Hz), 7.74 (s, 1H),
9.21 ppm (s, 1H); 13C NMR (CDCl3, 75 MHz): d=19.9, 56.1, 56.3, 95.4,
107.6, 112.5, 125.5, 128.5, 128.6, 129.4, 130.5, 133.6, 134.1, 136.5, 137.4,
144.1, 151.1, 171.1 ppm; HRMS (electrospray) calcd for C18H18NO3
[M+H]+: 296.1281, found: 296.1281.
3H), 4.00 (s, 3H), 6.38 (d, 1H, J=16.1 Hz), 7.11 (d, 1H, J=8.5 Hz), 7.61
(d, 1H, J=15.9 Hz), 7.68 (dd, 1H, J=2.1, 8.8 Hz), 8.00 ppm (d, 1H, J=
2.1 Hz); 13C NMR (CDCl3, 50 MHz): d=51.8, 56.7, 113.8, 118.4, 124.9,
127.0, 133.4, 141.7, 154.0, 166.8 ppm; MS (EI): m/z 237 [M], 206
[MꢀOCH3].
(E)-3-(4-methoxycarbonylbenzylidene)oxindole (10b): Purification by
flash chromatography (5% EtOAc/CH2Cl2 then 10% EtOAc/CH2Cl2)
gave 10b (126 mg, 45%) as a yellow solid. M.p. 234–2368C (Lit.[31] 238–
2398C); IR (KBr): n˜ =1609, 1625, 1701, 1715, 2953, 3021, 3077,
(E)-Methyl 2-methylcinnamate (8e): Purification by flash chromatogra-
phy (10% AcOEt- petroleum ether) gave 8e as a colorless oil (143 mg,
81%). IR (neat): n˜ =1634, 1718, 2950 cmꢀ1 1H NMR (CDCl3, 250 MHz):
;
d=2.44 (s, 3H), 3.81 (s, 3H), 6.36 (d, 1H, J=15.9 Hz), 7.18–7.31 (m,
3H), 7.55 (d, 1H, J=7.3 Hz), 7.99 ppm (d, 1H, J=15.9 Hz); 13C NMR
(CDCl3, 50 MHz): d=51.8, 120.6, 125.3, 127.8, 127.7, 131.2, 133.4, 134.4,
143.1, 166.8 ppm; MS (EI): m/z 176 [M], 145 [MꢀOCH3].
3141 cmꢀ1 1H NMR (DMSO, 300 MHz): d=3.88 (s, 3H), 6.81–6.88 (m,
;
2H), 7.24 (app t, 1H, J=7.9 Hz), 7.42 (d, 1H, J=7.5 Hz), 7.64 (s, 1H),
7.81 (d, 2H, J=7.9 Hz), 8.07 (d, 2H, J=8.3 Hz), 10.7 ppm (s, 1H);
13C NMR (DMSO, 75 MHz): d=52.3, 110.3, 120.5, 121.3, 122.7, 129.2,
129.5, 130.0, 130.7, 134.1, 139.3, 143.3, 165.7, 168.3 ppm; HRMS (electro-
spray) calcd for C17H14NO3 [M+H]+: 280.0973, found: 280.0977.
(E)-Methyl 4-methoxycarbonylcinnamate (3): Purification by flash chro-
matography (15% AcOEt/petroleum ether) gave 3 as a white solid
(205 mg, 93%). M.p. 1248C (Lit.[30] 122–1238C). IR (KBr): n˜ =1641,
(E)-3-(2-Bromobenzylidene)oxindole (10c): Purification by flash chroma-
tography (5% EtOAc/CH2Cl2 then 10% EtOAc/CH2Cl2) gave 10c
(180 mg, 60%) as a yellow solid. M.p. 1828C (Lit.[32] 166–1678C); IR
1720, 2958 cmꢀ1 1H NMR (CDCl3, 250 MHz): d=3.81 (s, 3H), 3.92 (s,
;
3H), 6.51 (d, 1H, J=15.9 Hz), 7.57 (d, 2H, J=8.5 Hz), 7.70 (d, 1H, J=
16.1 Hz), 8.04 ppm (d, 1H, J=8.2 Hz); 13C NMR (CDCl3, 75 MHz): d=
51.8, 52.2, 120.1, 127.9, 130.0, 131.3, 138.5, 143.4, 166.4, 166.9 ppm; MS
(EI): m/z 220 [M], 189 [MꢀOCH3].
General procedure for the preparation of oxindoles from acrylates
(Table 6): 10% Pd/C was added to a solution of the corresponding acry-
late (1 mmol) in MeOH (2.5 mL) (5 mol%), and the resulting mixture
stirred at 408C under H2 for 48 h. After filtration, the crude product was
purified by flash chromatography to give the corresponding oxindoles.
(KBr): n˜ =1615, 1714, 2840, 2900, 3006, 3027, 3081, 3145 cmꢀ1 1H NMR
;
(CDCl3, 300 MHz): d=6.82 (app t, 1H, J=7.9 Hz), 6.96 (d, 1H, J=
7.9 Hz), 7.19–7.34 (m, 3H), 7.41 (app t, 1H, J=7.1 Hz), 7.71 (d, 2H, J=
7.9 Hz), 7.82 (s, 1H), 9.37 ppm (s, 1H); 13C NMR (CDCl3, 75 MHz): d=
110.5, 121.3, 121.8, 123.1, 124.2, 127.2, 129.0, 130.2, 130.8, 133.2, 135.4,
135.8, 142.0, 170.1 ppm; HRMS (electrospray) calcd for C15H11NOBr
[M+H]+: 300.0018, found: 300.0013.
Computational details: Calculations were performed with the Gaussi-
an 03 suite of programs[33] using the hybrid functional B3LYP,[34,35] which
is a three-parameter functional developed by Becke that combines the
Becke gradient-corrected exchange functional and the Lee–Yang–Parr
and Vosko–Wilk–Nusair correlation functionals with the exact part of the
HF exchange energy. Pd was treated with a Stuttgart–Dresden pseudopo-
tential in combination with its adapted basis set.[36] Oxygen, nitrogen,
3-(4-Methoxycarbonylbenzyl)oxindole (9a): Purification by flash chroma-
tography (40% EtOAc/petroleum ether) gave 9a as
(228 mg, 81% yield). M.p. 1568C; IR (KBr): n˜ =1701, 1719, 2956, 3035,
3080, 3179 cmꢀ1 1H NMR (CDCl3, 250 MHz): d=3.05 (dd, 1H, J=8.7,
a white solid
;
13.8 Hz), 3.51 (dd, 1H, J=4.8, 13.7 Hz), 3.78 (dd, 1H, J=4.8, 8.7 Hz),
3.89 (s, 3H), 6.76–6.94 (m, 3H), 7.14–7.26 (m, 3H), 7.91 (d, 2H, J=
8.1 Hz), 8.94 ppm (brs, 1H); 13C NMR (CDCl3, 75 MHz): d=36.4, 47.1,
52.0, 109.8, 122.1, 124.6, 128.1, 128.4, 128.6, 129.5, 129.6, 141.4, 143.1,
167.0, 179.2 ppm; HRMS (electrospray) calcd for C17H15NO3Na
[M+Na]+: 304.0944, found: 304.0942.
carbon, and hydrogen atoms were described with a 6-31GACTHNUTRGNE(UNG d,p) double-z
basis set.[37] Geometry optimizations were carried out without any sym-
metry restrictions, the nature of the extrema (minimum or TS) was veri-
fied with analytical frequency calculations. All total energies and Gibbs
free energies were corrected for zero-point energy (ZPE) and tempera-
ture by using unscaled density functional frequencies. The connection be-
tween the transition states and the corresponding minima was confirmed
by IRC calculations.[38] The electronic structure was studied by natural
bond orbital (NBO) analysis.[39] Molecular structures were drawn with
Molekel 4.3.[40] Energies in solution reported in Figure 3 result from
single-point energy calculations with the solvent (methanol) effect taken
into account through the polarisable continuum model (PCM) imple-
mented in Gaussian 03.[41]
3-(2,4,6-Trimethylbenzyl)oxindole (9b): Purification by flash chromatog-
raphy (30% EtOAc/petroleum ether) gave 9b as a white solid (260 mg,
98% yield). M.p. 2068C; IR (KBr): n˜ =1622, 1707, 2961, 3002, 3031,
3079, 3176 cmꢀ1 1H NMR (CDCl3, 300 MHz): d=2.18 (s, 3H), 2.32 (s,
;
3H), 2.90 (dd, 1H, J=11.7, 13.9 Hz), 3.45 (dd, 1H, J=5.6, 13.9 Hz), 3.71
(dd, 1H, J=5.6, 11.7 Hz), 6.33 (d, 1H, J=7.5 Hz), 6.80 (t, 1H, J=
7.5 Hz), 6.89 (s, 2H), 6.95 (t, 1H, J=7.5 Hz), 7.18 (t, 1H, J=7.7 Hz),
9.26 ppm (brs, 1H); 13C NMR (CDCl3, 75 MHz): d=20.2, 20.9, 30.6, 44.8,
109.7, 121.9, 125.0, 127.8, 128.9, 129.2, 131.8, 136.0, 137.0, 141.4,
180.4 ppm; HRMS (electrospray) calcd for C18H19NONa [M+Na]+:
288.1358, found: 288.1356.
X-ray crystallography: CCDC-753309 (7c) contains the crystallographic
data for this paper. These data can be obtained free of charge from The
Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_-
request/cif.
3-Benzyl-6-phenyloxindole (9c): Purification by flash chromatography
(15% EtOAc/CH2Cl2) gave 9c as a white solid (218 mg, 73% yield). M.p.
1558C; IR (KBr): n˜ =1627, 1698, 3027, 3061, 3089, 3159 cmꢀ1 1H NMR
;
(CDCl3, 250 MHz): d=2.95 (dd, 1H, J=9.5, 13.7 Hz), 3.56 (dd, 1H, J=
4.3, 13.9 Hz), 3.81 (dd, 1H, J=4.6, 9.5 Hz), 6.77 (d, 1H, J=7.5 Hz), 7.11–
7.15 (m, 2H), 7.25–7.45 (m, 9H), 7.54 (d, 2H, J=7.9 Hz), 9.05 ppm (brs,
1H); 13C NMR (CDCl3, 75 MHz): d=36.7, 47.5, 108.6, 120.9, 125.0, 126.7,
127.0, 127.4, 128.0, 128.4, 128.7, 129.4, 137.8, 140.7, 141.3, 142.1,
5202
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Chem. Eur. J. 2010, 16, 5191 – 5204

Heck Reactions of Aryl Diazonium Salts
FULL PAPER
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Acknowledgements
This work was supported by the Universitꢀ de Bordeaux and the Centre
National de la Recherche Scientifique (CNRS). The theoretical work was
granted access to the HPC resources of IDRIS under allocation 2009
(i2009080045) made by GENCI (Grand Equipement National de Calcul
Intensif). We also acknowledge Prof. Jean-Cyrille Hierso (ICMUB,
UMR-CNRS 5260, Universitꢀ de Bourgogne) for the gift of ferrocenyl-
phosphine ligands, Dr. Brice Kauffmann (IECB, UMS-CNRS 3033, Uni-
versitꢀ de Bordeaux) for X-ray diffraction studies, and Mrs. Claire
Mouche (CESAMO, Universitꢀ de Bordeaux) for HRMS analyses. Dr.
Marion Zanese (Fluofarma, Bordeaux) is gratefully acknowledged for
fruitful discussions.
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Received: November 5, 2009
Published online: April 1, 2010
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Chem. Eur. J. 2010, 16, 5191 – 5204