Palladium-acetate catalyst for regioselective direct arylation at C2 of 3-furanyl or 3-thiophenyl acrylates with inhibition of Heck type reaction

Article abstract of DOI:10.1016/j.tet.2012.12.061

Pd(OAc)₂/KOAc was found to be an efficient catalytic system for the direct arylation of thiophene and furan derivatives bearing an acrylate at C3. The selectivity of the reaction strongly depends on the nature of the coordinating base. Na₂

Full text of DOI:10.1016/j.tet.2012.12.061

Tetrahedron 69 (2013) 4381e4388
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Palladium-acetate catalyst for regioselective direct arylation at C2
of 3-furanyl or 3-thiophenyl acrylates with inhibition of Heck type
reaction
*
Lu Chen, Christian Bruneau, Pierre H. Dixneuf, Henri Doucet
ꢀ
ꢀ
ꢀ
Institut des Sciences Chimiques de Rennes, UMR 6226, CNRS-Universite de Rennes, “Organometalliques: Materiaux et Catalyse”, Campus de Beaulieu,
35042 Rennes, France
a r t i c l e i n f o
a b s t r a c t
Article history:
Pd(OAc)2/KOAc was found to be an efficient catalytic system for the direct arylation of thiophene and
furan derivatives bearing an acrylate at C3. The selectivity of the reaction strongly depends on the nature
of the coordinating base. Na2CO3 and Li2CO3 favours the Heck type reaction; whereas the use of KOAc or
CsOAc promotes regioselective arylation at C2 of the heteroarene and inhibits the Heck type reaction. The
direct arylation products were obtained in moderate to good yields using only 0.1 mol % of catalyst.
Electron-withdrawing substituent on aryl bromide, such as acetyl, formyl, ester, nitrile or nitro, favours
the reaction; whereas electron-donating ones are unfavourable.
Received 6 November 2012
Received in revised form 19 December 2012
Accepted 21 December 2012
Available online 5 January 2013
Keywords:
Palladium
Catalysis
Ó 2013 Elsevier Ltd. All rights reserved.
Heteroarenes
Aryl bromides
CeH functionalisation
1. Introduction
HO
CO2H
O
Cl
HO
OH
Orpanoxin
Substituted thiophenes or furans, including arylated or viny-
lated ones, continue to attract the attention of synthetic organic
chemists, due to their inherent biological properties. For example,
Pizotifen is used to reduce migraine headaches, Orpanoxin is
a nonsteroidal anti-inflammatory drug, Nalfurafine a drug for the
treatment of uraemic pruritus, Ketotifen an antihistamine drug, and
Canagliflozin is an experimental drug for the treatment of type two
diabetes (Fig. 1).
Conventional methods for the introduction of aryl substituents
on such heteroaromatics include metal catalysed cross-coupling
reactions, such as Suzuki, Stille or Negishi type reactions,1 which
make possible the coupling of aryl halides with organometallic
derivatives of thiophenes or furans. However, they require the
preliminary preparation of a requisite organometallic species. Ohta
and co-workers reported in 1990 that the direct arylation of several
heteroaromatics with aryl halides via a CeH bond activation pro-
ceed in moderate to good yields using Pd(PPh3)4 as the catalyst.2
Since this report, the palladium-catalysed direct arylation of thio-
phenes or furans derivatives with aryl halides has proven to be
a cost-effective and environmentally attractive method for the
synthesis of a wide variety of arylated heterocycles.3e7
N
O
O
N
N
Nalfurafine
HO
HO
O
HO
S
Pizotifen
N
O
HO
S
F
S
Canagliflozin
Ketotifen
O
Fig. 1. Examples of bioactive furan or thiophene derivatives.
However, so far, the palladium-catalysed regiocontrolled direct
arylation of 3-substituted thiophenes or furans has attracted less
attention.6,7 In 2003 Sharp and co-workers reported conditions that
allowed the regioselective arylation of methyl 3-thiophene carbox-
ylate.7a The use of Pd(PPh3)4 in toluene selectivelygave the 2-arylated
thiophene; whereas, Pd2(dba)3 in NMP gave a mixture of 2- and
* Corresponding author. E-mail address: henri.doucet@univ-rennes1.fr (H. Doucet).
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2012.12.061

4382
L. Chen et al. / Tetrahedron 69 (2013) 4381e4388
5-arylated thiophenes in a 15:51 ratio. Bilodeau and co-workers have
examined the regioselectivity of the arylation of 3-methylthiophene
with bromobenzene using Pd[(P(t-Bu)3)]2 as the catalyst. They ob-
tained a mixture of the 2- and 5-phenylated thiophenes in a 3.3/1
ratio (30% yield of 2-phenylation and 9% yield of the 5-phenylated
thiophene).7b Recently, Fagnou and co-workers have reported the
direct arylation of 3-n-hexylthiophene with 4-bromonitrobenzene.7c
A mixture of C2 and C5 arylation products was obtained in a 1.3:1
ratio. The direct arylation of 3-methoxythiophene has been explored
by Borghese and co-workers.6b With this reactant, the 2-arylated
thiophenes were regioselectively obtained in 28e60% yields. Thus,
for palladium-catalysed direct arylations of 3-substituted thiophenes
or furans, mixtures of C2 and C5 arylated products were often ob-
tained, and the influence of the nature of the C3 substituents on the
regioselectivity remains largely unexplored.
We have recently reported that Pd(OAc)2 associated to potas-
sium carbonate efficiently catalyses the direct 5-arylation of furans
or thiophenes bearing enal, enone or acrylate functions at carbon
C2, with inhibition of the Heck type reaction. The nature of the base
was found to be crucial to control the selectivity of the arylation.15
In the presence of potassium carbonate as the base, the direct
arylation at C5 is favoured; whereas the use of potassium fluoride
selectively gave the Heck type product.
lacrylate with 4-bromobenzonitrile using KOAc as the base gave the
C2-arylated thiophene 1a as the major product in 87% selectivity.
The C5-arylated thiophene 1b was also obtained in 11% selectivity;
whereas, only trace amount of the Heck type products 1c were
observed (Table 1, entry 1). A very similar regioselectivity was ob-
served in the presence of CsOAc as the base (Table 1, entry 2). On the
other hand, NaOAc gave a mixture of C2- and C5-arylated products
1aþ1b and Heck type product 1c in 81:13 ratio (Table 1, entry 3).
This difference of selectivity might arise from a stronger interaction
of the acetate anion with Naþ cation than with Kþ or Csþ in DMAc.
Consequently, the transfer of the acetate to the palladium(II) would
be faster with KOAc or CsOAc than with NaOAc and this should fa-
vour a CeH concerted metallation deprotonation mechanism.17a,b
With nBu4NOAc as the base, 1c was the major product (Table 1,
entry 9). K2CO3, Cs2CO3, KF, and (NH4)2CO3 also led to mixtures of
products (Table 1, entries 4, 5, 8, and 10). It should be noted that the
use of Na2CO3 or Li2CO3 allows the access to the Heck type products
1c (ZþE stereoisomers) in 80% or 83% selectivities. Then, Z isomer of
1c was isolated in 42% or 40% yields, respectively (Table 1, entries 6
and 7). This result seems to confirm a slower transfer of the car-
bonate to palladium(II) with Liþ or Naþ cations than with Kþ or Csþ,
which might be due to the poor solubility of Na2CO3 or Li2CO3 in
DMAc.17c Such slow carbonate transfer favours Heck type reaction.
Then, we examined the influence of the solvent. Both NMP and
DMF led to similar results as DMAc; whereas, poor selectivities
were observed in dioxane, cyclopentyl methyl ether, xylene or
diethyl carbonate (Table 1, entries 11e15 and 17). The use of xylene
associated to Na2CO3 gave a mixture of 1c and 1d in a 9:91 ratio.
Moreover, a very low conversion of 4-bromobenzonitrile was ob-
served (Table 1, entry 16). We also examined the influence of the
nature and loading of the catalyst. The use of only 0.1 mol %
Pd(OAc)2 or ½ [PdCl(C3H5)]2 gave 1a in 88% and 86% selectivity and
in 68% and 66% yields showing that the dppb ligand is not really
needed (Table 1, entries 21 and 22). Finally, the influence of the
reaction temperature was examined. At more elevated or lower
temperatures (110 and 150 ꢀC), very similar selectivities were ob-
served. However, at 110 ꢀC, the conversion of 4-bromobenzonitrile
was only 92% (Table 1, entries 23 and 24).
To our knowledge, the intermolecular palladium-catalysed di-
rect arylation of thiophenes or furans bearing acrylate functions at
carbon C3 has not been reported (Scheme 1, bottom). This is cer-
tainly due to the possible competitive Heck reaction with such
substrates.8e11 Heck reactions with benzalacetone, cinnamates or
chalcone, proceed nicely.12e14 Moreover, an example of Heck type
reaction of 3-thiophen-3-ylacrylamide with iodobenzene has been
described by Park and co-workers (Scheme 1, top).16
Previous work16
O
NH2
Pd(OAc)2 4 mol%
P(o-tol)3
NH2
I
+
O
Then, the scope of the coupling of methyl (E)-3-(thiophen-3-y)
lacrylate using other aryl bromides was investigated (Scheme 3, Table
2). These reactions were performed using DMAc, AcOK, 130 ꢀC, and
DMF, NEt3, 72 h
S
S
51%
0.5e0.1 mol
% Pd(OAc)2 as the catalytic system. From 4-
This work
bromobenzaldehyde and 4-bromoacetophenone, the C2-arylated
thiophenes 2 and 3 were only obtained in moderate yields due to
partial decomposition of the reactants or products (Table 2, entries 1
and 2). On the other hand, good yields of 63% and 69% were obtained
from methyl 4-bromobenzoate and 4-bromonitrobenzene (Table 2,
entries 3 and 4). The reactivity of meta- and ortho-substituted aryl
bromides was also examined. From 3-bromobenzonitrile and 3-
bromonitrobenzene, products 6 and 7 were obtained in 61% and
69% yields, respectively;whereas, fromthemore congested substrate,
2-bromobenzonitrile product 8 was isolated in only 46% yield (Table
2, entries 5e7). It should be noted that, in all cases, a highly regio-
selective reaction in favour of the direct arylation at C2 was observed.
We also extended the scope of the Heck type reaction with
methyl (E)-3-(thiophen-3-y)lacrylate using 4-bromoacetophenone
and 4-bromobenzaldehyde and Na2CO3 as the base (Scheme 2). In
both cases the desired Heck type products were selectively ob-
tained as a mixture of Z and E isomers (Ratio Z:E¼3:2). Purification
on silica gel chromatography gave the Z isomers 9 and 10 in pure
forms. For this reaction, PdCl(C3H5)(dppb) 2 mol % was used as the
catalyst in the presence of Na2CO3 as the base.
CO2Me
CO2Me
Pd(OAc)2
[Pd]
Y
R
KOAc or
+
Na2CO3 or
Li2CO3
CO2Me
Y
CsOAc
R
Y
Br
Y = O or S
Scheme 1.
Here, we wish to report that Pd(OAc)2 in association with KOAc
or CsOAc as the base/ligand provides an efficient catalyst for the
regioselective direct arylation at C2 with inhibition of the non-
desired Heck type reaction of methyl (E)-3-(thiophen-3-yl)acry-
late and methyl (E)-3-(furan-3-yl)acrylate using a variety of aryl
bromides.
2. Results and discussion
For this study, based on previous results,15 DMAc was chosen as
the solvent. The reactions were performed at 130 ꢀC under argon in
the presence 2 mol % of PdCl(C3H5)(dppb) as the catalyst. Using
these conditions, the coupling of methyl (E)-3-(thiophen-3-y)
Then, the reactivity of methyl (E)-3-(furan-3-yl)acrylate was
examined (Table 3). Again, a good yield in C2-arylated furan 11
was obtained in the presence of 4-bromobenzonitrile and 0.1 mol %
Pd(OAc)2/KOAc as the catalytic system (Table 3, entry 1). Similar

L. Chen et al. / Tetrahedron 69 (2013) 4381e4388
4383
Table 1
Influence of the reaction conditions for palladium-catalysed coupling of methyl (E)-3-(thiophen-3-yl)acrylate with 4-bromobenzonitrile
NC
CO2Me
CO2Me
CO2Me
[Pd]
NC
Br
+
130 °C, 17 h
NC
CN
S
S
S
CO2Me
1c
CN
NC
1b
1a
1d
S
Entry
Catalyst (mol %)
Solvent
Base
Conversion of
4-bromobenzonitrile (%)
Ratio
1a:1b:1c:1d (%)
Yield in 1a
or 1c (%)
1
2
3
4
5
6
7
8
PdCl(C3H5)(dppb) (2)
PdCl(C3H5)(dppb) (2)
PdCl(C3H5)(dppb) (2)
PdCl(C3H5)(dppb) (2)
PdCl(C3H5)(dppb) (2)
PdCl(C3H5)(dppb) (2)
PdCl(C3H5)(dppb) (2)
PdCl(C3H5)(dppb) (2)
PdCl(C3H5)(dppb) (2)
PdCl(C3H5)(dppb) (2)
PdCl(C3H5)(dppb) (2)
PdCl(C3H5)(dppb) (2)
PdCl(C3H5)(dppb) (2)
PdCl(C3H5)(dppb) (2)
DMAc
DMAc
DMAc
DMAc
DMAc
DMAc
DMAc
DMAc
DMAc
DMAc
NMP
KOAc
100
85
88
64
97
97
100
30
31
7
87:11:1:1
85:12:1:2
73:10:13:4
37:10:14:39
39:9:26:26
5:1:80:14
2:0:83:15
43:7:35:15
30:0:60:10
0:0:85:15
86:11:1:2
85:10:2:3
64:14:16:6
54:14:28:4
67a
65a
d
CsOAc
NaOAc
Cs2CO3
K2CO3
Na2CO3
Li2CO3
KF
d
d
42b
40b
d
9
nBu4NOAc
(NH4)2CO3
KOAc
KOAc
KOAc
d
10
11
12
13
14
d
100
100
100
100
d
DMF
Dioxane
d
d
Cyclopentyl
methyl ether
Xylene
Xylene
Diethyl
carbonate
DMAc
DMAc
DMAc
DMAc
DMAc
KOAc
d
15
16
17
PdCl(C3H5)(dppb) (2)
PdCl(C3H5)(dppb) (2)
PdCl(C3H5)(dppb) (2)
KOAc
Na2CO3
KOAc
100
11
100
32:7:58:3
0:0:9:91
44:12:37:7
d
d
d
15
16
17
21
22
23
24
Pd(OAc)2 (2)
PdCl2 (2)
KOAc
KOAc
KOAc
KOAc
KOAc
KOAc
KOAc
100
100
100
100
100
100
92
84:10:1:5
84:9:1:6
86:10:1:3
88:11:1:0
86:13:1:0
89:6:1:4
88:6:1:5
d
d
½ [PdCl(C3H5)]2 (2)
Pd(OAc)2 (0.1)
½ [PdCl(C3H5)]2 (0.1)
Pd(OAc)2 (0.1)
Pd(OAc)2 (0.1)
d
71a
69a
dc
dd
DMAc
DMAc
Conditions: methyl (E)-3-(thiophen-3-yl)acrylate (2 equiv), 4-bromobenzonitrile (1 equiv), base (2 equiv), 130 ꢀC, 17 h, yield of 1a.
a
Isolated yield of 1a.
b
Isolated yield of Z isomer of 1c.
c
Reaction temperature 150 ꢀC.
d
Reaction temperature 110 ꢀC.
yields were obtained from 4-bromoacetophenone and 4-bromo-
nitrobenzene (Table 3, entries 3 and 4). On the other hand, from 4-
bromobenzaldehyde, 12 was only obtained in 42% yield due to
some decomposition of the reactants (Table 3, entry 2). A poor yield
in 15 was also obtained in the presence of the electron-rich 4-
bromoanisole due to a partial conversion of this aryl bromide
(Table 3, entry 5). Both 3-bromobenzonitrile and 3-bromo-
nitrobenzene were successfully coupled to methyl (E)-3-furan-3-
ylacrylate to give 16 and 17 in good yields (Table 3, entries 7 and
8). A lower reactivity of 1-bromonaphthalene was observed. With
this reactant, a higher catalyst loading of 0.5 mol % had to be
employed in order to obtain high conversion of the aryl bromide
to produce 20 in 62% yield (Table 3, entry 11). Finally, 3-
bromopyridine was employed as the coupling partner. In the
presence of 0.1 mol % Pd(OAc)2 as the catalyst, only trace of 19 was
detected. On the other hand, the use of 2 mol % PdCl(C3H5)(dppb)
led to 21 in 58% yield (Table 3, entries 12 and 13).
The use of Na2CO3 as the base for the reaction of methyl (E)-3-
(furan-3-yl)acrylate with 4-bromobenzaldehyde also produced
very selectively the Heck type products as a mixture of Z and E
stereoisomers (Z:E ratio¼3:2); whereas, 12 was detected in less
than 2%. The Z isomer 22 could be isolated in 46% yield (Scheme 3).
In summary, we have demonstrated that the selectivity of
palladium-acetate catalysed reaction of 3-thiophen-3-ylacrylate
and 3-furan-3-ylacrylate with aryl bromides strongly depends on
the nature of the coordinating base. The use of Na2CO3 or Li2CO3
selectively led to the Heck type products, whereas, KOAc or CsOAc
promotes regioselective direct arylation at C2 of the heteroarene.
This complete change in selectivity might come from a stronger
interaction of the acetate or carbonate anion with Liþ or Naþ cation
than with Kþ or Csþ in DMAc, thus avoiding the acetate to play its
coordinating ligand/base role for CeH bond deprotonation. These
direct arylations can generally be performed using low catalyst
loadings (0.5e0.1 mol %) of a commercially available air-stable and
phosphine-free catalyst. Electron-withdrawing substituent on the
aryl bromide, such as acetyl or nitrile favours the reaction; whereas
electron-donating substituents are unfavourable. A range of func-
tions, such as acetyl, formyl, ester, nitro or nitrile on the aryl bro-
mide is tolerated. This reaction allows the synthesis in only one step
of a variety of 2-arylated furans or thiophenes bearing acrylates at
carbon 3 without preparation of organometallic derivatives. Finally,
due to environmental considerations, the advantage of such inert
wastes procedure (formation of acetic acid and potassium bromide)
should become increasingly important for industrial processes.
3. Experimental
3.1. General remarks
All reactions were run under argon in Schlenk tubes using
vacuum lines. DMAc (N,N-dimethylacetamide) (99%) was pur-
chased from Acros. KOAc (99%), Pd(OAc)2 (45.9e48.4%), [Pd(C3H5)

4384
L. Chen et al. / Tetrahedron 69 (2013) 4381e4388
Table 2
Table 3
Scope of the palladium-catalysed direct arylation of methyl (E)-3-thiophen-3-yl-
Scope of the palladium-catalysed direct arylation of methyl (E)-3-(furan-3-yl)
acrylate
acrylate
CO2Me
CO2Me
CO2Me
CO2Me
R
Pd(OAc)2
Pd(OAc)2
R
0.1 or 0.5 mol%
0.1 or 0.5 mol%
+
+
Br
Br
R
R
DMAc, KOAc,
130 °C, 17 h
DMAc, KOAc,
130 °C, 17 h
S
O
S
O
2-8
11-21
Entry
1
Aryl bromide
Product
Yield (%)
40
Entry
1
Aryl bromide
Product
CO2Me
Yield (%)
70
CO2Me
Br
CHO
Br
CN
S
O
CHO
CN
2
11
12
13
14
CO2Me
CO2Me
2
3
4
5
46
63
Br
COMe
S
2
3
4
42
73
76
Br
CHO
COMe
NO2
COMe
3
O
CHO
CO2Me
Br
CO2Me
CO2Me
S
CO2Me
4
Br
O
CO2Me
COMe
69
Br
NO2
S
CO2Me
NO2
5
Br
CO2Me
CN
CN
O
NO2
61a
Br
S
6
CO2Me
CO2Me
NO2
NO2
5
6
Trace
16a
Br
OMe
6
7
69
46
O
Br
OMe
S
15
7
CO2Me
CN
CO2Me
CN
NC
7
8
66
75
Br
O
Br
S
16
NC
8
Conditions: Pd(OAc)2 0.1 mol %, methyl (E)-3-(thiophen-3-y)lacrylate (2 equiv), aryl
bromide (1 equiv), KOAc (2 equiv), DMAc, 130 ꢀC, 17 h.
CO2Me
NO2
NO2
a
Pd(OAc)2 0.5 mol %.
Br
O
17
R
CO2Me
COMe
COMe
CO2Me
9
52
57
PdCl(C3H5)(dppb)
2 mol%
Br
O
18
R
Br
+
DMAc, Na2CO3,
130 °C, 17 h
CO2Me
S
CO2Me
S
NC
R
Product Yield (%)
10
COMe
CHO
52
45
9
Br
O
10
NC
19
Scheme 2.

L. Chen et al. / Tetrahedron 69 (2013) 4381e4388
4385
(d, J¼5.1 Hz, 1H), 6.28 (d, J¼15.9 Hz, 1H), 3.70 (s, 3H). 13C NMR
Table 3 (continued )
(75 MHz, CDCl3) d 167.4, 143.3, 137.7, 136.4, 133.9, 132.6, 130.2, 126.7,
Entry
Aryl bromide
Product
CO2Me
Yield (%)
126.6, 119.6, 118.5, 112.0, 51.8. Elemental analysis: calcd (%) for
C15H11NO2S (269.32): C 66.89, H 4.12; found: C 66.70, H 4.01.
3.3.2. Methyl (Z)-3-(4-cyanophenyl)-3-(thiophen-3-yl)acrylate (1c).
From 4-bromobenzonitrile (0.182 g, 1 mmol), methyl (E)-3-(thio-
phen-3-y)lacrylate (0.336 g, 2 mmol), and Na2CO3 as the base
(0.212 g, 2 mmol), product 1c was obtained in 42% (0.113 g) yield.
11
62b
O
Br
Br
20
21
1H NMR (400 MHz, CDCl3)
d
7.66 (d, J¼8.1 Hz, 2H), 7.44 (d,
J¼8.1 Hz, 2H), 7.37 (dd, J¼5.0, 3.0 Hz, 1H), 7.32 (dd, J¼3.0, 1.3 Hz,
CO2Me
12
13
Trace
58a
1H), 7.02 (dd, J¼5.0, 1.3 Hz, 1H), 6.29 (s, 1H), 3.72 (s, 3H). 13C NMR
(100 MHz, CDCl3)
d 165.9, 148.8, 145.7, 137.2, 132.2, 129.0, 128.9,
N
127.0, 125.2, 119.5, 118.4, 112.9, 51.6. Elemental analysis: calcd (%)
for C15H11NO2S (269.32): C 66.89, H 4.12; found: C 66.99, H 4.25.
The formation of methyl (E)-3-[(4-cyanophenyl)-3-thiophen-3-yl]
acrylate was also observed before purification, but was not ob-
O
N
Conditions: Pd(OAc)2 0.1 mol %, methyl (E)-3-(furan-3-yl)acrylate (2 equiv), aryl
bromide (1 equiv), KOAc (2 equiv), DMAc, 130 ꢀC, 17 h.
tained in pure form: 1H NMR (400 MHz, CDCl3)
(s, 3H).
d 6.46 (s, 1H), 3.62
a
PdCl(C3H5)(dppb) 2 mol %, 150 ꢀC.
Pd(OAc)2 0.5 mol %, 150 ꢀC.
b
3.3.3. Methyl (E)-3-[2-(4-formylphenyl)-thiophen-3-yl]acrylate (2).
From 4-bromobenzaldehyde (0.185 g, 1 mmol) and methyl (E)-3-
(thiophen-3-y)lacrylate (0.336 g, 2 mmol), product 2 was obtained
in 40% (0.109 g) yield.
O
CO2Me
PdCl(C3H5)(dppb)
1H NMR (300 MHz, CDCl3)
d
10.09 (s, 1H), 7.98 (d, J¼8.1 Hz, 2H),
O
2 mol%
Br
+
7.69 (d, J¼15.9 Hz, 1H), 7.61 (d, J¼8.1 Hz, 2H), 7.40 (d, J¼5.1 Hz, 1H),
DMAc, Na2CO3,
150 °C, 17 h
CO2Me
22 46%
O
7.38 (d, J¼5.1 Hz, 1H), 6.37 (d, J¼15.9 Hz, 1H), 3.79 (s, 3H). 13C NMR
(75 MHz, CDCl3) d 191.6, 167.5, 144.2, 139.1, 136.8, 135.8, 133.7, 130.3,
O
130.2, 126.5, 126.4, 119.3, 51.7. Elemental analysis: calcd (%) for
C15H12O3S (272.32): C 66.16, H 4.44; found: C 66.04, H 4.59.
Scheme 3.
Cl]2 (56.5%), and dppb [1,4-bis(diphenylphosphino)butane] (98%)
were purchased from Alfa Aesar. Commercial aryl bromides and
heteroarenes were used without purification. The reactions were
followed by GC and NMR spectroscopic analysis. 1H and 13C spectra
were recorded with Bruker 300 or 400 MHz spectrometers.
Chemical shifts are reported in parts per million relative to CDCl3
(7.25 for 1H NMR and 77.0 for 13C NMR). Flash chromatography was
performed on silica gel (230e400 mesh).
3.3.4. Methyl (E)-3-[2-(4-acetylphenyl)-thiophen-3-yl]acrylate (3).
From 4-bromoacetophenone (0.199 g, 1 mmol) and methyl (E)-3-
(thiophen-3-y)lacrylate (0.336 g, 2 mmol), product 3 was obtained
in 46% (0.131 g) yield.
1H NMR (400 MHz, CDCl3)
d
7.97 (d, J¼8.1 Hz, 2H), 7.69 (d,
J¼15.9 Hz,1H), 7.61 (d, J¼8.1 Hz, 2H), 7.28 (s, 2H), 6.27 (d, J¼15.9 Hz,
1H), 3.70 (s, 3H), 2.57 (s, 3H). 13C NMR (75 MHz, CDCl3)
197.4,
d
167.6, 144.6, 137.7, 137.0, 136.6, 133.5, 129.9, 128.8, 126.3, 126.2,
119.0, 51.7, 26.7. Elemental analysis: calcd (%) for C16H14O3S
(286.35): C 67.11, H 4.93; found: C 67.35, H 4.98.
3.2. Preparation of the PdCl(C3H5)(dppb) catalyst18
An oven-dried 40 mL Schlenk tube equipped with a magnetic
stirring bar under argon atmosphere, was charged with [Pd(C3H5)
Cl]2 (182 mg, 0.5 mmol) and ppb (426 mg, 1 mmol). 10 mL of an-
hydrous dichloromethane were added, then, the solution was
stirred at room temperature for 20 min. The solvent was removed
in vacuo. The yellow powder was used without purification. 31P
3.3.5. Methyl (E)-4-[3-(2-methoxycarbonylvinyl)-thiophen-2-yl]ac-
rylate (4). From methyl 4-bromobenzoate (0.215 g, 1 mmol) and
methyl (E)-3-(thiophen-3-y)lacrylate (0.336 g, 2 mmol), product 4
was obtained in 63% (0.190 g) yield.
1H NMR (400 MHz, CDCl3)
d
8.04 (d, J¼8.1 Hz, 2H), 7.60 (d,
J¼15.9 Hz,1H), 7.43 (d, J¼8.1 Hz, 2H), 7.28 (s, 2H), 6.26 (d, J¼15.9 Hz,
1H), 3.88 (s, 3H), 3.69 (s, 3H). 13C NMR (75 MHz, CDCl3)
167.5,
NMR (81 MHz, CDCl3)
d
¼19.3 (s).
d
166.6, 144.7, 137.6, 137.0, 133.4, 130.1, 129.9, 129.7, 126.3, 126.1, 119.0,
52.3, 51.7. Elemental analysis: calcd (%) for C16H14O4S (302.35): C
63.56, H 4.67; found: C 63.68, H 4.50.
3.3. General procedure
In a typical experiment, the aryl bromide (1 mmol), hetero-
aromatic derivative (2 mmol), KOAc (0.196 g, 2 mmol), and
Pd(OAc)2 (0.22 mg, 0.001 mmol) or (1.1 mg, 0.005 mmol) or
PdCl(C3H5)(dppb) (13.6 mg, 0.02 mmol) (see tables), were dissolved
in DMAc (4 mL) under an argon atmosphere. The reaction mixture
was stirred at 130 ꢀC for 17 h. After evaporation of the solvent, the
product was purified by silica gel column chromatography.
3.3.6. Methyl (E)-3-[2-(4-nitrophenyl)-thiophen-3-yl]acrylate (5).
From 4-bromonitrobenzene (0.202 g, 1 mmol) and methyl (E)-3-
(thiophen-3-y)lacrylate (0.336 g, 2 mmol), product 5 was obtained
in 69% (0.199 g) yield.
1H NMR (300 MHz, CDCl3)
d
8.33 (d, J¼8.0 Hz, 2H), 7.63 (d,
J¼15.9 Hz, 1H), 7.61 (d, J¼8.0 Hz, 2H), 7.43 (d, J¼5.1 Hz, 1H), 7.40 (d,
J¼5.1 Hz,1H), 6.38 (d, J¼15.9 Hz,1H), 3.80 (s, 3H). 13C NMR (75 MHz,
3.3.1. Methyl (E)-3-[2-(4-cyanophenyl)thiophen-3-yl]acrylate (1a).
From 4-bromobenzonitrile (0.182 g, 1 mmol), methyl (E)-3-(thio-
phen-3-y)lacrylate (0.336 g, 2 mmol), and KOAc (0.196 g, 2 mmol)
as the base, product 1a was obtained in 71% (0.191 g) yield.
CDCl3) d 167.3, 147.5, 142.8, 139.6, 136.3, 134.2, 130.4, 127.3, 126.6,
124.1, 119.8, 51.8. Elemental analysis: calcd (%) for C14H11NO4S
(289.31): C 58.12, H 3.83; found: C 58.30, H 3.97.
1H NMR (400 MHz, CDCl3)
(d, J¼15.9 Hz, 1H), 7.45 (d, J¼8.1 Hz, 2H), 7.31 (d, J¼5.1 Hz, 1H), 7.28
d
7.66 (d, J¼8.1 Hz, 2H), 7.54
3.3.7. Methyl (E)-3-[2-(3-cyanophenyl)-thiophen-3-yl]acrylate (6).
From 3-bromobenzonitrile (0.182 g,
1 mmol) and methyl

4386
L. Chen et al. / Tetrahedron 69 (2013) 4381e4388
(E)-3-(thiophen-3-y)lacrylate (0.336 g, 2 mmol), product 6 was
(furan-3-yl)acrylate (0.304 g, 2 mmol), product 11 was obtained in
obtained in 61% (0.164 g) yield.
70% (0.177 g) yield.
1H NMR (300 MHz, CDCl3)
d
7.75e7.50 (m, 5H), 7.39 (d, J¼5.1 Hz,
1H NMR (400 MHz, CDCl3)
d
7.73 (d, J¼15.9 Hz, 1H), 7.66 (s, 4H),
1H), 7.37 (d, J¼5.1 Hz, 1H), 6.36 (d, J¼15.9 Hz, 1H), 3.79 (s, 3H). 13C
7.45 (s, 1H), 6.65 (s, 1H), 6.24 (d, J¼15.9 Hz, 1H), 3.73 (s, 3H). 13C
NMR (75 MHz, CDCl3)
d
167.4, 142.9, 136.3, 134.5, 134.0, 133.7, 133.0,
NMR (100 MHz, CDCl3) d 167.1, 151.6, 143.8, 134.4, 134.0, 132.7, 127.2,
131.8, 129.8, 126.4, 126.3, 119.5, 118.2, 113.3, 51.8. Elemental analy-
sis: calcd (%) for C15H11NO2S (269.32): C 66.89, H 4.12; found: C
66.75, H 4.05.
120.2, 120.1, 118.5, 111.8, 110.2, 51.8. Elemental analysis: calcd (%) for
C15H11NO3 (253.25): C 71.14, H 4.38; found: C 71.31, H 4.19.
3.3.13. Methyl (E)-3-[2-(4-formylphenyl)-furan-3-yl]acrylate (12).
From 4-bromobenzaldehyde (0.185 g, 1 mmol) and methyl (E)-3-
(furan-3-yl)acrylate (0.304 g, 2 mmol), product 12 was obtained in
42% (0.108 g) yield.
3.3.8. Methyl (E)-3-[2-(3-nitrophenyl)-thiophen-3-yl]acrylate (7).
From 3-bromonitrobenzene (0.202 g, 1 mmol) and methyl (E)-3-
(thiophen-3-y)lacrylate (0.336 g, 2 mmol), product 7 was obtained
in 69% (0.199 g) yield.
1H NMR (400 MHz, CDCl3)
d
9.99 (s, 1H), 7.91 (d, J¼8.1 Hz, 2H),
1H NMR (400 MHz, CDCl3)
d
8.23 (s, 1H), 8.21 (d, J¼8.0 Hz, 1H),
7.80 (d, J¼15.9 Hz, 1H), 7.74 (d, J¼8.1 Hz, 2H), 7.46 (s, 1H), 6.66 (s,
7.68 (d, J¼7.8 Hz, 1H), 7.59 (t, J¼7.8 Hz, 1H), 7.52 (d, J¼15.9 Hz, 1H),
7.33 (d, J¼5.1 Hz, 1H), 7.30 (d, J¼5.1 Hz, 1H), 6.30 (d, J¼15.9 Hz, 1H),
1H), 6.25 (d, J¼15.9 Hz, 1H), 3.74 (s, 3H). 13C NMR (75 MHz, CDCl3)
d
191.5, 167.2, 152.4, 143.7, 135.7, 135.4, 134.8, 130.2, 127.4, 120.1,
3.70 (s, 3H). 13C NMR (75 MHz, CDCl3)
d
167.4, 142.7, 136.2, 135.6,
119.8, 110.1, 51.8. Elemental analysis: calcd (%) for C15H12O4
(256.25): C 70.31, H 4.72; found: C 70.11, H 4.89.
134.8, 133.9, 129.9, 126.5, 126.3, 124.5, 123.2, 119.6, 51.8. Elemental
analysis: calcd (%) for C14H11NO4S (289.31): C 58.12, H 3.83; found:
C 58.09, H 3.68.
3.3.14. Methyl (E)-3-[2-(4-acetylphenyl)-furan-3-yl]acrylate (13).
From 4-bromoacetophenone (0.199 g, 1 mmol) and methyl (E)-3-
(furan-3-yl)acrylate (0.304 g, 2 mmol), product 13 was obtained in
73% (0.197 g) yield.
3.3.9. Methyl (E)-3-[2-(2-cyanophenyl)-thiophen-3-yl]acrylate (8).
From 2-bromobenzonitrile (0.182 g, 1 mmol) and methyl (E)-3-
(thiophen-3-y)lacrylate (0.336 g, 2 mmol), product 8 was obtained
in 46% (0.124 g) yield.
1H NMR (300 MHz, CDCl3)
d
8.06 (d, J¼8.1 Hz, 2H), 7.87 (d,
J¼15.9 Hz, 1H), 7.74 (d, J¼8.1 Hz, 2H), 7.53 (d, J¼2.0 Hz, 1H), 6.73 (d,
1H NMR (400 MHz, CDCl3)
d
7.73 (d, J¼7.7 Hz, 1H), 7.60 (t,
J¼2.0 Hz, 1H), 6.31 (d, J¼15.9 Hz, 1H), 3.82 (s, 3H), 2.66 (s, 3H). 13C
J¼7.7 Hz, 1H), 7.47 (t, J¼7.7 Hz, 1H), 7.40 (d, J¼7.7 Hz, 1H), 7.36 (d,
NMR (75 MHz, CDCl3) d 197.3, 167.3, 152.8, 143.5, 136.5, 135.0, 134.1,
J¼5.1 Hz, 1H), 7.32 (d, J¼5.1 Hz, 1H), 7.31 (d, J¼15.9 Hz, 1H), 6.25 (d,
128.9, 127.0, 119.6, 119.4, 109.9, 51.8, 26.7. Elemental analysis: calcd
(%) for C16H14O4 (270.28): C 71.10, H 5.22; found: C 71.27, H 5.04.
J¼15.9 Hz, 1H), 3.67 (s, 3H). 13C NMR (75 MHz, CDCl3)
d 167.5, 140.4,
136.4, 136.3, 135.4, 133.7, 132.7, 132.2, 129.2, 127.1, 125.6, 119.2, 117.4,
113.9, 51.7. Elemental analysis: calcd (%) for C15H11NO2S (269.32): C
66.89, H 4.12; found: C 66.99, H 4.21.
3.3.15. Methyl (E)-3-[2-(4-nitrophenyl)-furan-3-yl]acrylate (14).
From 4-bromonitrobenzene (0.202 g, 1 mmol) and methyl (E)-3-
(furan-3-yl)acrylate (0.304 g, 2 mmol), product 14 was obtained in
76% (0.207 g) yield.
3.3.10. Methyl (Z)-3-(4-acetylphenyl)-3-(thiophen-3-yl)acrylate (9).
From 4-bromoacetophenone (0.199 g, 1 mmol), methyl (E)-3-(thi-
1H NMR (300 MHz, CDCl3)
d
8.34 (d, J¼7.5 Hz, 2H), 7.85 (d,
ophen-3-y)lacrylate (0.336 g,
2
mmol), and Na2CO3 as the
J¼15.9 Hz, 1H), 7.82 (d, J¼7.5 Hz, 2H), 7.56 (d, J¼2.0 Hz, 1H), 6.76 (d,
base (0.212 g, 2 mmol), product 9 was obtained in 52% (0.149 g)
J¼2.0 Hz,1H), 6.35 (d, J¼15.9 Hz,1H), 3.83 (s, 3H). 13C NMR (75 MHz,
yield.
CDCl3) d 167.1, 151.2, 144.1, 135.8, 134.3, 127.4, 124.3, 120.8, 120.5,
1H NMR (300 MHz, CDCl3)
d
7.95 (d, J¼8.6 Hz, 2H), 7.42 (d,
110.3, 51.9. Elemental analysis: calcd (%) for C14H11NO5 (273.24): C
61.54, H 4.06; found: C 61.69, H 4.14.
J¼8.6 Hz, 2H), 7.36 (dd, J¼5.0, 3.0 Hz, 1H), 7.32 (dd, J¼3.0, 1.3 Hz,
1H), 7.03 (dd, J¼5.0,1.3 Hz,1H), 6.32 (s,1H), 3.71 (s, 3H), 2.63 (s, 3H).
13C NMR (100 MHz, CDCl3)
d
197.5, 166.2, 149.8, 145.8, 137.7, 137.5,
3.3.16. Methyl (E)-3-[2-(4-methoxyphenyl)-furan-3-yl]acrylate (15).
From 4-bromoanisole (0.187 g, 1 mmol) and methyl (E)-3-(furan-3-
yl)acrylate (0.304 g, 2 mmol), product 15 was obtained in 16%
(0.041 g) yield.
129.1, 128.5, 128.4, 126.8, 124.9, 118.7, 51.5, 26.7. Elemental analysis:
calcd (%) for C16H14O3S (286.35): C 67.11, H 4.93; found: C 67.40, H
4.87. The formation of methyl (E)-3-(4-acetylphenyl)-3-thiophen-3-
ylacrylate was also observed before purification, but was not ob-
1H NMR (400 MHz, CDCl3)
d
7.75 (d, J¼15.9 Hz, 1H), 7.49 (d,
tained in pure form: 1H NMR (400 MHz, CDCl3)
(s, 3H), 2.53 (s, 3H).
d
6.36 (s, 1H), 3.52
J¼8.5 Hz, 2H), 7.34 (s,1H), 6.93 (d, J¼8.5 Hz, 2H), 6.58 (s,1H), 6.14 (d,
J¼15.9 Hz, 1H), 3.79 (s, 3H), 3.71 (s, 3H). 13C NMR (75 MHz, CDCl3)
d
167.7, 160.1, 154.9, 142.1, 136.1, 128.8, 122.7, 117.4, 116.8, 114.4,
3.3.11. Methyl (Z)-3-(4-formylphenyl)-3-(thiophen-3-yl)acrylate (10).
From 4-bromobenzaldehyde (0.185 g, 1 mmol), methyl (E)-3-(thio-
phen-3-y)lacrylate (0.336 g, 2 mmol), and Na2CO3 as the base
(0.212 g, 2 mmol), product 10 was obtained in 45% (0.122 g) yield.
109.2, 55.4, 51.6. Elemental analysis: calcd (%) for C15H14O4
(258.27): C 69.76, H 5.46; found: C 69.89, H 5.60.
3.3.17. Methyl (E)-3-[2-(3-cyanophenyl)-furan-3-yl]acrylate (16).
From 3-bromobenzonitrile (0.182 g, 1 mmol) and methyl (E)-3-
(furan-3-yl)acrylate (0.304 g, 2 mmol), product 16 was obtained in
66% (0.167 g) yield.
1H NMR (400 MHz, CDCl3)
d
9.97 (s, 1H), 7.79 (d, J¼8.6 Hz, 2H),
7.41 (d, J¼8.6 Hz, 2H), 7.28 (dd, J¼5.0, 3.0 Hz, 1H), 7.24 (d, J¼3.0 Hz,
1H), 6.94 (d, J¼5.0 Hz, 1H), 6.24 (s, 1H), 3.63 (s, 3H). 13C NMR
(75 MHz, CDCl3)
d
191.6, 166.0, 149.6, 147.1, 137.6, 136.7, 129.6, 129.0,
1H NMR (400 MHz, CDCl3)
d
7.85 (s, 1H), 7.77 (d, J¼7.6 Hz, 1H),
128.9, 126.8, 125.0, 119.2, 51.6. Elemental analysis: calcd (%) for
C15H12O3S (272.32): C 66.16, H 4.44; found: C 66.41, H 4.64. The
formation of methyl (E)-3-(4-formylphenyl)-3-(thiophen-3-yl)acry-
late was also observed before purification, but was not obtained in
7.70 (d, J¼15.9 Hz, 1H), 7.60 (d, J¼7.6 Hz, 1H), 7.52 (t, J¼7.6 Hz, 1H),
7.44 (s, 1H), 6.64 (s, 1H), 6.23 (d, J¼15.9 Hz, 1H), 3.74 (s, 3H). 13C
NMR (100 MHz, CDCl3) d 167.1, 151.4, 143.5, 134.3, 131.8, 131.3, 131.1,
130.4, 129.8, 119.9, 119.4, 118.2, 113.4, 109.9, 51.8. Elemental analy-
sis: calcd (%) for C15H11NO3 (253.25): C 71.14, H 4.38; found: C 71.08,
H 4.54.
pure form: 1H NMR (400 MHz, CDCl3)
3.52 (s, 3H).
d 10.01 (s, 1H), 6.38 (s, 1H),
3.3.12. Methyl (E)-3-[2-(4-cyanophenyl)-furan-3-yl]acrylate (11).
From 4-bromobenzonitrile (0.182 g, 1 mmol) and methyl (E)-3-
3.3.18. Methyl (E)-3-[2-(3-nitrophenyl)-furan-3-yl]acrylate (17).
From 3-bromonitrobenzene (0.202 g,
1 mmol) and methyl

L. Chen et al. / Tetrahedron 69 (2013) 4381e4388
4387
(E)-3-(furan-3-yl)acrylate (0.304 g, 2 mmol), product 17 was ob-
(m, 1H), 7.44 (d, J¼8.6 Hz, 2H), 7.02 (m, 1H), 6.65 (dd, J¼2.0, 0.9 Hz,
tained in 75% (0.205 g) yield.
1H), 6.30 (s, 1H), 3.61 (s, 3H).
1H NMR (400 MHz, CDCl3)
d
8.44 (s, 1H), 8.17 (d, J¼7.6 Hz, 1H),
7.86 (d, J¼7.6 Hz, 1H), 7.74 (d, J¼15.9 Hz, 1H), 7.59 (t, J¼7.6 Hz, 1H),
Acknowledgements
7.46 (s, 1H), 6.66 (s, 1H), 6.25 (d, J¼15.9 Hz, 1H), 3.74 (s, 3H). 13C
NMR (75 MHz, CDCl3) d 167.1, 151.3, 143.6, 134.2, 132.6, 131.6, 130.0,
We are grateful to the Chinese Scholarship Council for a PhD
grant to L.C. We thank the Centre National de la Recherche Scien-
tifique and ‘Rennes Metropole’ for providing financial support.
123.1,121.8,120.0, 119.7,109.9, 51.8. Elemental analysis: calcd (%) for
C14H11NO5 (273.24): C 61.54, H 4.06; found: C 61.31, H 4.20.
3.3.19. Methyl (E)-3-[2-(3-acetylphenyl)-furan-3-yl]acrylate (18).
From 3-bromoacetophenone (0.199 g, 1 mmol) and methyl (E)-3-
(furan-3-yl)acrylate (0.304 g, 2 mmol), product 18 was obtained in
52% (0.140 g) yield.
References and notes
1. (a) Li, J. J.; Gribble, G. W. Palladium in Heterocyclic Chemistry; Pergamon:
Amsterdam, 2000.
2. (a) Ohta, A.; Akita, Y.; Ohkuwa, T.; Chiba, M.; Fukunaga, R.; Miyafuji, A.; Nakata,
T.; Tani, N.; Aoyagi, Y. Heterocycles 1990, 31, 1951e1958; (b) Aoyagi, Y.; Inoue, A.;
Koizumi, I.; Hashimoto, R.; Miyafuji, A.; Kunoh, J.; Honma, R.; Akita, Y.; Ohta, A.
Heterocycles 1992, 33, 257e272.
1H NMR (400 MHz, CDCl3)
d
8.14 (s, 1H), 7.91 (d, J¼7.6 Hz, 1H),
7.76 (d, J¼15.9 Hz, 1H), 7.73 (d, J¼7.6 Hz, 1H), 7.51 (t, J¼7.6 Hz, 1H),
7.42 (s, 1H), 6.64 (s, 1H), 6.21 (d, J¼15.9 Hz, 1H), 3.73 (s, 3H), 2.59 (s,
3. (a) Satoh, T.; Miura, M. Chem. Lett. 2007, 36, 200e205; (b) Campeau, L.-C.; Stuart,
D. R.; Fagnou, K. Aldrichimica Acta 2007, 40, 35e41; (c) Seregin, I. V.; Gevorgyan, V.
Chem. Soc. Rev. 2007, 36,1173e1193; (d) Li, B.-J.; Yang, S.-D.; Shi, Z.-J. Synlett 2008,
949e957; (e) Bellina, F.; Rossi, R. Tetrahedron 2009, 65, 10269e10310; (f)
Ackermann, L.; Vincente, R.; Kapdi, A. R. Angew. Chem., Int. Ed. 2009, 48,
9792e9826; (g) Roger, J.; Gottumukkala, A. L.; Doucet, H. ChemCatChem 2010, 2,
20e40; (h) Fischmeister, C.; Doucet, H. Green Chem. 2011, 13, 741e753.
4. For recent examples of direct arylations of thiophenes: (a) David, E.; Pellet-
Rostaing, S.; Lemaire, M. Tetrahedron 2007, 63, 8999e9006; (b) Amaladass, P.;
Clement, J. A.; Mohanakrishnan, A. K. Tetrahedron 2007, 63, 10363e10371; (c)
Nakano, M.; Tsurugi, H.; Satoh, T.; Miura, M. Org. Lett. 2008, 10, 1851e1854; (d)
3H). 13C NMR (100 MHz, CDCl3)
d 196.5, 166.3, 152.2, 142.0, 136.7,
134.1, 130.5, 129.5, 128.2, 127.2, 126.1, 117.9, 117.6, 108.6, 50.7, 25.7.
Elemental analysis: calcd (%) for C16H14O4 (270.28): C 71.10, H 5.22;
found: C 71.01, H 5.30.
3.3.20. Methyl (E)-3-[2-(2-cyanophenyl)-furan-3-yl]acrylate (19).
From 2-bromobenzonitrile (0.182 g, 1 mmol) and methyl (E)-3-
(furan-3-yl)acrylate (0.304 g, 2 mmol), product 19 was obtained in
57% (0.144 g) yield.
ꢀ
Liegaut, B.; Lapointe, D.; Caron, L.; Vlassova, A.; Fagnou, K. J. Org. Chem. 2009,
74, 1826e1834; (e) Yanagisawa, S.; Ueda, K.; Sekizawa, H.; Itami, K. J. Am. Chem.
Soc. 2009, 131, 14622e14623; (f) Ueda, K.; Yanagisawa, S.; Yamaguchi, J.; Itami,
K. Angew. Chem., Int. Ed. 2010, 49, 8946e8949; (g) Derridj, F.; Roger, J.; Djebbar,
S.; Doucet, H. Org. Lett. 2010, 12, 4320e4323; (h) Dong, J. J.; Roger, J.; Verrier, C.;
Martin, T.; Le Goff, R.; Hoarau, C.; Doucet, H. Green Chem. 2010, 12, 2053e2063;
(i) Tanaka, S.; Tamba, S.; Tanaka, D.; Sugie, A.; Mori, A. J. Am. Chem. Soc. 2011,
133, 9700e9703; (j) Baghbanzadeh, M.; Pilger, C.; Kappe, C. O. J. Org. Chem.
2011, 76, 8138e8142; (k) Tang, S.-Y.; Guo, Q.-X.; Fu, Y. Chem.dEur. J. 2011, 17,
13866e13876; (l) Beydoun, K.; Zaarour, M.; Williams, J. A. G.; Doucet, H.;
Guerchais, V. Chem. Commun. 2012, 1260e1262; (m) Chen, L.; Bruneau, C.;
Dixneuf, P. H.; Doucet, H. Green Chem. 2012, 14, 1111e1124.
5. For examples of direct arylations of furans: (a) McClure, M. S.; Glover, B.;
McSorley, E.; Millar, A.; Osterhout, M. H.; Roschangar, F. Org. Lett. 2001, 3,
1677e1680; (b) Parisien, M.; Valette, D.; Fagnou, K. J. Org. Chem. 2005, 70,
7578e7584; (c) Lindahl, K.-F.; Carroll, A.; Quinn, R. J.; Ripper, J. A. Tetrahedron Lett.
2006, 47, 7493e7495; (d) Beccalli, E. M.; Broggini, G.; Martinelli, M.; Sottocornola,
1H NMR (400 MHz, CDCl3)
d
7.75 (d, J¼7.6 Hz, 1H), 7.63 (t,
J¼7.6 Hz,1H), 7.55e7.42 (m, 4H), 6.68 (s,1H), 6.23 (d, J¼15.9 Hz,1H),
3.71 (s, 3H). 13C NMR (75 MHz, CDCl3)
167.2, 150.7, 144.2, 134.5,
d
134.3, 132.8, 132.6, 130.5, 129.3, 120.8, 119.5, 117.7, 111.8, 109.3, 51.7.
Elemental analysis: calcd (%) for C15H11NO3 (253.25): C 71.14, H
4.38; found: C 71.19, H 4.58.
3.3.21. Methyl (E)-3-(2-naphthalen-1-ylfuran-3-yl)acrylate (20).
From 1-bromonaphthalene (0.207 g, 1 mmol) and methyl (E)-3-
(furan-3-yl)acrylate (0.304 g, 2 mmol), product 20 was obtained in
62% (0.172 g) yield.
1H NMR (400 MHz, CDCl3)
d 7.90e7.75 (m, 3H), 7.55e7.40 (m,
6H), 6.72 (s, 1H), 6.16 (d, J¼15.9 Hz, 1H), 3.64 (s, 3H). 13C NMR
ꢀ
S. Synthesis 2008, 136e140; (e) Smaliy, R. V.; Beauperin, M.; Cattey, H.; Meunier,
P.; Hierso, J.-C.; Roger, J.; Doucet, H.; Coppel, Y. Organometallics 2009, 28,
3152e3160; (f) Fu, H. Y.; Doucet, H. Eur. J. Org. Chem. 2011, 7163e7173.
6. For intermolecular arylations at C2 of 3-substituted thiophenes: (a) Lavenot, L.;
Gozzi, C.; Ilg, K.; Orlova, I.; Penalva, V.; Lemaire, M. J. Organomet. Chem. 1998,
567, 49e55; (b) Borghese, A.; Geldhof, G.; Antoine, L. Tetrahedron Lett. 2006, 47,
9249e9252; (c) Fournier Dit Chabert, J.; Marquez, B.; Neville, L.; Joucla, L.;
Broussous, S.; Bouhours, P.; David, E.; Pellet-Rostaing, S.; Marquet, B.; Moreau,
N.; Lemaire, M. Bioorg. Med. Chem. 2007, 15, 4482e4497; (d) Rene, O.; Fagnou,
K. Org. Lett. 2010, 9, 2116e2119; (e) Takeda, D.; Yamashita, M.; Hirano, K.; Satoh,
T.; Miura, M. Chem. Lett. 2011, 40, 1015e1017.
(100 MHz, CDCl3)
d 167.5, 155.2, 143.2, 135.8, 133.8, 131.9, 130.2,
129.3, 128.4, 126.9, 126.8, 126.3, 125.7, 125.2, 120.2, 117.6, 108.7, 51.5.
Elemental analysis: calcd (%) for C18H14O3 (278.30): C 77.68, H 5.07;
found: C 77.51, H 4.87.
3.3.22. Methyl (E)-3-(2-pyridin-3-ylfuran-3-yl)acrylate (21). From
3-bromopyridine (0.158 g, 1 mmol) and methyl (E)-3-(furan-3-yl)
acrylate (0.304 g, 2 mmol), product 21 was obtained in 58% (0.133 g)
yield.
7. For intermolecular arylations at C5 of 3-substituted thiophenes or furans: (a)
Glover, B.; Harvey, K. A.; Liu, B.; Sharp, M. J.; Tymoschenko, M. F. Org. Lett. 2003,
5, 301e304; (b) Forgione, P.; Brochu, M.-C.; St-Onge, M.; Thesen, K. H.; Bailey,
1H NMR (400 MHz, CDCl3)
d
8.83 (s, 1H), 8.56 (d, J¼3.9 Hz, 1H),
ꢀ
M. D.; Bilodeau, F. J. Am. Chem. Soc. 2006, 128, 11350e11351; (c) Liegault, B.;
7.85 (d, J¼7.7 Hz, 1H), 7.72 (d, J¼15.9 Hz, 1H), 7.43 (s, 1H), 7.34 (dd,
Petrov, I.; Gorlesky, S. I.; Fagnou, K. J. Org. Chem. 2010, 75, 1047e1060; (d) Dong,
J. J.; Doucet, H. Eur. J. Org. Chem. 2010, 611e615; (e) Dong, J. J.; Roy, D.; Jacob Roy,
R.; Ionita, M.; Doucet, H. Synthesis 2011, 3530e3546; (f) Tanaka, S.; Tamba, S.;
Tanaka, D.; Sugie, A.; Mori, A. J. Am. Chem. Soc. 2011, 133, 16734e16737; (g)
Kamiya, H.; Yanagisawa, S.; Hiroto, S.; Itami, K.; Shinokubo, H. Org. Lett. 2011, 13,
6394e6397.
8. For a review on Heck reaction: Withcombe, N.; Hii, K. K.; Gibson, S. Tetrahedron
2001, 57, 7449e7476.
9. Lage, S.; Martinez-Estibalez, U.; Sotomayor, N.; Lete, E. Adv. Synth. Catal. 2009,
351, 2460e2468.
10. Arai, N.; Miyaoku, T.; Teruya, S.; Mori, A. Tetrahedron Lett. 2008, 49, 1000e1003.
11. For an intramolecular cyclization of a 3-vinyl-substituted benzothiophene:
Ohno, H.; Iuchi, M.; Kojima, N.; Yoshimitsu, T.; Fujii, N.; Tanaka, T. Chem.dEur. J.
2012, 18, 5352e5360.
12. For examples of Heck reactions using benzalacetone or chalcone derivatives:
(a) Amorese, A.; Arcadi, A.; Bernocchi, E.; Cacchi, S.; Cerrini, S.; Fereli, W.; Ortar,
G. Tetrahedron 1989, 45, 813e828; (b) Kondolff, I.; Doucet, H.; Santelli, M.
Tetrahedron Lett. 2003, 44, 8487e8491; (c) Calo, V.; Nacci, A.; Monopoli, A.;
Cotugno, P. Angew. Chem., Int. Ed. 2009, 48, 6101e6103.
13. For examples of Heck reactions using cinnamaldehyde: (a) Bagnell, L.; Kreher,
U.; Strauss, C. R. Chem. Commun. 2001, 29e30; (b) Aggarwal, V. K.; Staubitz, A.
C.; Owen, M. Org. Process Res. Dev. 2006, 10, 64e69; (c) Stadler, M.; List, B.
Synlett 2008, 597e599.
J¼7.7, 3.9 Hz, 1H), 6.65 (s, 1H), 6.23 (d, J¼15.9 Hz, 1H), 3.73 (s, 3H).
13C NMR (75 MHz, CDCl3)
d 167.2, 151.2, 149.5, 148.1, 143.6, 134.5,
134.2, 126.3, 123.6, 119.4, 119.3, 109.7, 51.7. Elemental analysis: calcd
(%) for C13H11NO3 (229.23): C 68.11, H 4.84; found: C 68.23, H 4.71.
3.3.23. Methyl (Z)-3-[(4-formylphenyl)-3-furan-3-yl]acrylate (22).
From 4-bromobenzaldehyde (0.185 g, 1 mmol), methyl (E)-3-(fu-
ran-3-yl)acrylate (0.304 g, 2 mmol), and Na2CO3 as the base
(0.212 g, 2 mmol), product 22 was obtained in 46% (0.118 g) yield.
1H NMR (300 MHz, CDCl3)
d
10.06 (s, 1H), 7.89 (d, J¼8.6 Hz, 2H),
7.65 (m, 1H), 7.56 (d, J¼8.6 Hz, 2H), 7.47 (m, 1H), 7.28 (d, J¼0.6 Hz,
1H), 6.50 (m, 1H), 6.16 (s, 1H), 3.76 (s, 3H). 13C NMR (75 MHz, CDCl3)
d
191.6, 166.0, 147.5, 146.0, 144.9, 142.6, 136.6, 129.6, 129.1, 122.0,
118.7, 112.0, 51.5. Elemental analysis: calcd (%) for C15H12O4
(256.25): C 70.31, H 4.72; found: C 70.51, H 4.60. Methyl (E)-3-[(4-
formylphenyl)-3-furan-3-yl]acrylate was also isolated in low yield:
1H NMR (300 MHz, CDCl3)
d
10.08 (s,1H), 7.95 (d, J¼8.6 Hz, 2H), 7.47

4388
L. Chen et al. / Tetrahedron 69 (2013) 4381e4388
14. For examples of Heck reactions using cinnamates: (a) Busacca, C. A.; Johnson,
R. E. Tetrahedron Lett. 1992, 33, 165e168; (b) Moreno-Manas, M.; Perez, M.;
Pleixats, R. Tetrahedron Lett. 1996, 37, 7449e7452; (c) Gurtler, C.; Buchwald, S.
Chem.dEur. J. 1999, 5, 3107e3112; (d) Cacchi, S.; Fabrizi, G.; Gasparrini, F.; Pace,
P.; Villani, C. Synlett 2000, 650e652; (e) Littke, A.; Fu, G. J. Am. Chem. Soc. 2001,
123, 6989e7000; (f) Calo, V.; Nacci, A.; Monopoli, A.; Lopez, L.; di Cosmo, A.
Tetrahedron 2001, 57, 6071e6077; (g) Botella, L.; Najera, C. J. Org. Chem. 2005,
70, 4360e4369; (h) Johnson, P. D.; Sohn, J.-H.; Rawal, V. H. J. Org. Chem. 2006,
71, 7899e7902.
15. Chen, L.; Roger, J.; Bruneau, C.; Dixneuf, P. H.; Doucet, H. Adv. Synth. Catal. 2011,
353, 2749e2760.
16. Baek, G. H.; Cho, S. J.; Jung, Y. S.; Seong, C.-M.; Lee, C. W.; Park, N.-S. Bull. Korean
Chem. Soc. 1999, 20, 232e236.
17. (a) Davies, D. L.; Donald, S. M. A.; Macgregor, S. A. J. Am. Chem. Soc. 2005, 127,
13754e13755; (b) Lapointe, D.; Fagnou, K. Chem. Lett. 2010, 39, 1118e1126; (c)
Amatore, C.; Jutand, A.; Le Duc, G. Chem.dEur. J. 2012, 18, 6616e6625.
ꢀ
18. Cantat, T.; Genin, E.; Giroud, C.; Meyer, G.; Jutand, A. J. Organomet. Chem. 2003,
687, 365e376.