Phosphine-free palladium catalytic system for the selective direct arylation of furans or thiophenes bearing alkenes and inhibition of heck-type reaction

Article abstract of DOI:10.1002/adsc.201100193

Palladium acetate associated to potassium carbonate as catalytic system has been found to efficiently catalyse the direct 5-arylation of furans or thiophenes bearing enal, enone or acrylate functions at carbon C-2, and to inhibit the Heck-type reaction. The nature of the base is crucial to control the selectivity of the arylation. In the presence of electron-deficient aryl bromides and potassium carbonate as the base, the direct arylation is favoured, whereas the use of potassium fluoride gave selectively the Heck-type product, and tri-n-butylamine the reductive addition product. Copyright

Full text of DOI:10.1002/adsc.201100193

FULL PAPERS
DOI: 10.1002/adsc.201100193
Phosphine-Free Palladium Catalytic System for the Selective
Direct Arylation of Furans or Thiophenes bearing Alkenes and
Inhibition of Heck-Type Reaction
Lu Chen,a Julien Roger,a Christian Bruneau,a Pierre H. Dixneuf,a
and Henri Douceta,*
a
Institut Sciences Chimiques de Rennes, UMR 6226 CNRS, Universitꢀ de Rennes, “Catalyse et Organometalliques”,
Campus de Beaulieu, 35042 Rennes, France
Fax : (+33)-2-2323-6939; phone: (+33)-2-2323-6384; e-mail: henri.doucet@univ-rennes1.fr
Received: March 17, 2011; Revised: May 11, 2011; Published online: August 30, 2011
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adcs.201100193.
Abstract: Palladium acetate associated to potassium base, the direct arylation is favoured, whereas the
carbonate as catalytic system has been found to effi- use of potassium fluoride gave selectively the Heck-
ciently catalyse the direct 5-arylation of furans or type product, and tri-n-butylamine the reductive ad-
thioACHTUNGTRENNUNGphenes bearing enal, enone or acrylate functions dition product.
at carbon C-2, and to inhibit the Heck-type reaction.
The nature of the base is crucial to control the selec-
tivity of the arylation. In the presence of electron-de- Keywords: atom-economy; catalysis; C H activa-
À
ficient aryl bromides and potassium carbonate as the tion; heteroarenes; palladium
Introduction
competitive Heck reaction[11,12c] or the reductive addi-
tion on the alkene in the presence of amines[12]
Mixed biACHTUNGTRENNUNG(hetero)aryl derivatives display a set of bio- (Scheme 1). Heck reactions with benzalacetone, cin-
active or physical properties and their preparation namates or chalcone, proceed nicely in the presence
constitutes an active field of research in organic of carbonates as the base in DMF (a);[13–17] whereas
chemistry.[1] Several methods for the preparation of tertiary amines produces the reductive addition prod-
these products have been described. The palladium- ucts (b).[12d]
catalysed direct arylation of some heteroaromatics via
À
a C H bond activation using aryl halides has led to
successes in recent years.[2] For such direct coupling
reactions, no preparation of an organometallic deriva-
tive is required, and this is a tremendous advantage as
compared to the more classical cross-coupling proce-
dures arising from more costly Suzuki–Miyaura, Stille,
or Negishi reactions. Moreover, the direct arylation
reaction provides only an acid (HX) associated to a
required base as by-product and therefore presents
advantages both in terms of atom-economy and rela-
tively inert wastes. However, although this procedure
has been widely applied in recent years for the syn-
thesis of arylthiophenes,[3] arylfurans,[4] arylpyrroles,[5]
or other arylated heteroaromatics,[6–8] relatively few
arylated heteroaromatics bearing a functional alkene
À
as substituent have been prepared by direct C H
bond functionalisation.[9,10] This is due to the possible Scheme 1.
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Lu Chen et al.
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The control of the direct arylation of heteroaromat-
We first explored the activity of PdClACTHNGUTREN(NUG C3H5)ACHTUNGTRENNUNG(dppb)
ics bearing an alkene, without formation of competi- as we recently demonstrated that it was one of the
tive Heck-type products, would offer a strong poten- best catalysts for the direct arylation of some furans,
tial in organic synthesis since it would provide a more thiophenes or thiazoles.[3c,h] Using 1 mol% of
environmentally and economically attractive access to PdClACTHNUTGRENN(UG C3H5)ACHTUNGTNER(NUGN dppb) as the catalyst precursor, DMAc
conjugated compounds useful as materials due to as the solvent and KOAc or CsOAc as the base at
their optical properties such as for dye sensitized 1308C, the desired 5-arylation product 1a was ob-
solar cells.[18] So far, only a few examples of palladi- tained in 96% selectivity (Scheme 2, Table 1, entries 2
um-catalysed intramolecular cyclisations of 2-alkenyl- and 3). The Heck type product 1b was only produced
substituted N-(o-iodobenzyl)pyrroles employing thal- in 4% selectivity, and the reductive addition product
lium acetate as the base,[9] and the direct arylation of 1c was not detected. On the other hand, surprisingly
thiophenes bearing trisubstituted alkenes [2-(2,2-di- the use of NaOAc led mostly to the Heck-type prod-
ACHTUNGTRENNUNG
arylvinyl)-thiophenes][10] have been reported. To the uct 1b (Table 1, entry 1). This difference of selectivity
best of our knowledge, the general intermolecular might come from a stronger interaction of the acetate
direct arylation of heteroaromatics such as thiophenes anion with Na+ cation than with K+ or Cs+ in DMAc.
or furans bearing enal, enone or acrylate functions Consequently, the transfer of the acetate to the
has not been described.
palladiACTHNGUETRNNUuG m(II) would be faster with KOAc or CsOAc
We now report that PdACTHGUNTRNE(NUG OAc)2 catalyst in the pres- than with NaOAc and this should favour a concerted
ence of KOAc as the base controls the intermolecular metallation deprotonation mechanism.[19b] In the pres-
direct 5-arylation with aryl bromides of furans or thio- ence of carbonates as the bases, complete conversions
phenes bearing enal, enone or acrylate functions at of 4-bromobenzonitrile were observed, but only
carbon C-2 with inhibition of Heck-type reactions.
traces of product 1a were detected (Table 1, entries 4–
6). As KF was shown to favour Heck-type reactions
and to inhibit reductive addition,[12c] it has also been
evaluated. With this base, the Heck-type product 1b
was predominantly formed and isolated in 40% yield
Results and Discussion
As the nature of the base has been found in recent (Table 1, entry 7).
years to be a crucial factor to promote efficiently pal-
The nature of the solvent often modifies the cata-
ladium-[9,19] or ruthenium-catalysed[20] direct aryla- lyst activity in cross-coupling reactions, thus we ob-
tions, we could expect a drastic influence of the served that DMF gave 1a in high selectivity, but the
nature of the base, associated with that of the ligand, formation of 15% of biphenyl-4,4’-dicarbonitrile was
on the selectivity for the reaction of heteroaromatics also observed (Table 1, entry 8). NMP gave a mixture
bearing electron-poor alkenes with aryl bromides.
of several unidentified products (Table 1, entry 9),
First, we have considered the reaction of (E)-4- and dioxane and toluene led to poor conversions of 4-
furan-2-ylbut-3-en-2-one for the palladium-catalysed bromobenzonitrile and to equimolar mixtures of
coupling reaction with 4-bromobenzonitrile to reach products 1a and 1b (Table 1, entries 10 and 11). We
the formation of C-5 arylated product 1a (Scheme 2). then evaluated the influence of the palladium source.
As this substrate is similar to benzalacetone,[13] the Interestingly, Pd
ACTHUNRGTNENUG(OAc)2 and [PdClACHTUNGTNERN(UGN C3H5)]2 gave very
formation of Heck-type product 1b is possible.
selectively 1a (Table 1, entries 13 and 14). A few reac-
tions were also performed using palladium associated
to other phosphine ligands, and showed that the pres-
ence of such phosphines for the coupling with 4-bro-
mobenzonitrile was found to be useless, as the selec-
tivities in favour of the formation of 1a and the con-
versions of 4-bromobenzonitrile were not improved
(Table 1, entries 15–19). It should be noted that the
use of (n-Bu)3N as the base led to the predominant
formation of the reductive addition product 1c in
moderate yield (Table 1, entry 20). Thus it clearly ap-
pears that although PdCl
with KOAc in DMAc (Table 1, entry 3) to a decent
yield of 1a, the phosphine-free Pd(OAc)2 catalyst
ACHUTGTNRENUN(G C3H5)ACHTUGNTREN(NUGN dppb) 1 mol% leads
AHCTUNGTRENNUNG
(1 mol%) appears to be the most efficient for the pro-
duction of 1a. Moreover, the use of only 0.1 mol%
Pd
ACHTUNGRTENUN(NG OAc)2 gave 1a in 96% selectivity and in 74% yield
(Table 1, entry 21).
Scheme 2.
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Phosphine-Free Palladium Catalytic System for the Selective Direct Arylation of Furans or Thiophenes
Table 1. Influence of the reaction conditions for palladium-catalysed coupling of (E)-4-furan-2-ylbut-3-en-2-one with 4-bro-
mobenzonitrile (Scheme 2).[a]
Entry
[Pd] (mol%)
Temp. [8C]
Solvent
Base
Conv. [%]
Ratio 1a:1b
Yield in 1a [%]
1
2
3
4
5
6
7
8
PdCl
PdCl
PdCl
PdCl
PdCl
PdCl
PdCl
PdCl
PdCl
PdCl
PdCl
PdCl
N
G
130
130
130
130
130
130
130
130
130
130
130
100
130
130
130
130
130
130
130
150
130
DMAc
DMAc
DMAc
DMAc
DMAc
DMAc
DMAc
DMF
NaOAc
CsOAc
KOAc
Na2CO3
K2CO3
Cs2CO3
KF
KOAc
KOAc
KOAc
KOAc
KOAc
KOAc
KOAc
KOAc
KOAc
KOAc
KOAc
KOAc
100
100
100
100
100
100
100
100
57
29:71
96:4[b]
96:4
–
–
72
–
–
5:95[b]
mixture[c,d]
mixture[c,d]
3:97[b,c]
96:4[b]
mixture[c]
50:50
48:52
93:7
–
40[e]
–
9
NMP
–
–
–
–
–
–
–
–
10
11
12
13
14
15
16
17
18
19
20
21
dioxane
toluene
DMAc
DMAc
DMAc
DMAc
DMAc
DMAc
DMAc
DMAc
DMAc
DMAc
46
41
48
Pd
N
100
100
100
100
100
100
100
88
96:4
0.5 [PdCl
0.5 [PdCl
N
E
96:4[d]
92:8[d]
96:4[d]
78:22
94:6[d]
92:8
Pd
Pd(OAc)2/dppm
Pd(OAc)2/dppb
A
N
T
–
–
PdCl
PdCl
N
A
–
96:4
47[f]
74
Pd
N
100
[a]
Conditions: 4-bromobenzonitrile (1 equiv.), (E)-4-furan-2-ylbut-3-en-2-one (2 equiv.), base (2 equiv.), 17 h, GC and NMR
conversion of 4-bromobenzonitrile, yields of isolated product.
The formation of 10–20% of biphenyl-4,4’-dicarbonitrile was also observed.
The formation of several products was observed.
The formation of more than 20% of biphenyl-4,4’-dicarbonitrile was also observed.
Product 1b was isolated in 40% yield.
[b]
[c]
[d]
[e]
[f]
1a not detected, product 1c was isolated in 47% yield.
The scope of the coupling of (E)-4-furan-2-ylbut-3- bromides, 3-bromoacetophenone, 3-bromonitroben-
en-2-one using other aryl bromides was investigated zene or 3-bromobenzonitrile. With these aryl bro-
using low amounts of Pd(OAc)2 catalyst (Scheme 3, mides, the direct arylation products 4a–6a were pro-
Table 2). These reactions were performed using duced in 83–90% selectivity and isolated in 49–73%
DMAc, AcOK, 1308C and 0.5–0.1 mol% Pd(OAc)2. yields (Table 2, entries 4–6). On the other hand, in the
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
First, we studied the reactivity of para-substituted aryl presence of the electron-rich aryl bromide, 4-bromoa-
bromides. In the presence of electron-deficient aryl nisole, an inversion of the regioselectivity of the aryla-
bromides such as ethyl 4-bromobenzoate or 4-bromo- tion in favour of the Heck-type coupling product 8b
nitrobenzene, the products 2a and 3a were isolated in was observed (Table 2, entry 8). It is likely that with
52% and 57% yields, respectively (Table 2, entries 1 donating groups on arenes, the more nucleophilic aryl
and 2). A similar reactivity and regioselectivity was group interacts first with the electrophilic carbon of
observed in the presence of the meta-substituted aryl the enone. By contrast, with electrophilic ArPdACHTUNGTRENNUNG(OAc)
moieties, the interaction with the furan HC-5=C-4
À
bond is favoured to lead to the C H bond deprotona-
tion by acetate.[19] Although an electrophilic aromatic-
type substitution cannot be ruled out,[2b] however, the
assistance of carboxylate ligand on palladium for the
arylation of heterocycles has been demonstrated by
Fagnou.[19b] As we have observed a strong influence of
the acetate with very small amounts of PdACTHNURGTNEUNG(OAc)2, the
concerted metallation deprotonation mechanism is
preferred in these examples.
The influence of the nature of the double bond sub-
stituents on the selectivity and activity also needed to
be evaluated. The reactivity of cinnamaldehyde in the
Scheme 3.
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Table 2. Palladium-catalysed direct coupling of (E)-4-furan- Table 3. Palladium-catalysed direct coupling of (E)-3-furan-2-yl-
2-ylbut-3-en-2-one with aryl bromides (Scheme 3).[a]
propenal with aryl bromides (Scheme 3).[a]
Entry Ratio Major product
Yield of a Entry Base
Ratio Major product
Yield of
a:b
[%]
a:b
a (%)
1
KOAc
96:4
64
1
77:23
52
2
3
4
5
6
7
KOAc
KOAc
KOAc
KOAc
KOAc
KOAc
96:4
97:3
96:4
78:22
93:7
95:5
68
2
3
4
91:9
57[b]
75[c]
51
92:8
83:17
74
66
5
6
7
90:10
88:12
94:6
73
52
49[b]
70
71
73[b]
8
–
25[d]
8
KOAc
0:100
35[c]
41[d]
[a]
Conditions: PdCAHTUNGTRENNUNG
(1 equiv.),
(E)-4-furan-2-ylbut-3-en-2-one
9
NaHCO3 0:100
Conditions: Pd
(E)-3-furan-2-ylpropenal (2 equiv.), AcOK or NaHCO3
(2 equiv.), DMAc, 17 h, 1308C.
PdClACHTUNTRGENN(UG C3H5)ACHUTNGTREN(NUGN dppb) (0.01 equiv.).
41 h, Ratio of Heck-type products Z:E 19:81, yield of 16b.
Ratio of Heck-type products Z:E 22:78, yield of 16b.
AcOK (2 equiv.), DMAc, 17 h, 1308C.
[b]
[c]
[d]
Pd
PdCl
Yield of isomer 8b.
ACHTUNGTRENNUNG
[a]
(OAc)2 (0.001 equiv.), aryl bromide (1 equiv.),
A
ACHTUNGTRENNUNG
[b]
[c]
[d]
presence of aryl halides has already been described,
and in that case, the Heck-type products were easily
obtained.[14] We observed that the coupling of (E)-3-
furan-2-ylpropenal with electron-deficient aryl bro-
mides, under the activation by Pd
ACHTUNGRTEN(NGNU OAc)2/KOAc, gave
the direct arylation products 9a–12a, 14a and 15a with
The reaction of methyl (E)-3-furan-2-yl acrylate
high selectivities, and that in several cases, higher se- with aryl bromides in the presence of PdACHTUNRGTNEUNG(OAc)2 was
lectivities than for the coupling with (E)-4-furan-2- found to give the direct arylation products 17a–22a in
ylbut-3-en-2-one were observed (Table 3). Again, the extremely high selectivity in several cases. This result
electron-rich aryl bromide, 4-bromoanisole, gave the was quite surprising as the Heck reaction with cinna-
Heck type product 16b selectively (Table 3, entries 8 mates is known to be relatively easy. For example, the
and 9). From the E isomer, a mixture of Z and E iso- reaction of ethyl cinnamate with 4-bromotoluene in
mers was obtained in 22:78 ratio.
the presence of only 0.1 mol% of [PdClACTHNGUTERNNU(G C3H5)]2/tetra-
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Phosphine-Free Palladium Catalytic System for the Selective Direct Arylation of Furans or Thiophenes
Table 4. Palladium-catalysed direct coupling of methyl (E)-
3-furan-2-yl acrylate with aryl bromides (Scheme 3).[a]
Entry Ratio Major product
Yield of a
a:b
[%]
1
2
3
95:5
91:9
97:3
81
67
82
Scheme 4.
4
5
86:14
83:17
65
62
66
Scheme 5.
6
96:4
fully employed. Even 1-bromonaphthalene was found
to be a suitable reactant for this reaction (Table 5,
entry 10). It is noteworthy that 3-bromopyridine, 3-
bromoisoquinoline or 4-bromoisoquinoline led to 73–
83% of direct arylation products 33a–35a without poi-
soning of the catalyst by coordination of the pyridine
group (Table 5, entries 11–13). However, with these
[a]
Conditions: PdACHTNUTRGNE(NUG OAc)2 (0.005 equiv.), aryl bromide
(1 equiv.), methyl (E)-3-furan-2-yl acrylate (2 equiv.),
AcOK (2 equiv.), DMAc, 17 h, 1508C.
phosphine as the catalyst, K2CO3 as the base in DMF three substrates 0.5 mol% catalyst had to be em-
gives the Heck product in 91% yield.[13b] In the pres- ployed in order to reach full conversions of these aryl
ence of methyl (E)-3-furan-2-yl acrylate, and bromides.
0.5 mol% Pd
G
On the other hand, the coupling of 2-bromobenzo-
zene, 2- or 4-bromobenzonitrile or 1-bromobenzalde- nitrile with (E)-4-thien-2-ylbut-3-en-2-one gave the
hyde gave more than 90% of the 5-arylated furans target compound 36a in only 58% yield due to the
17a–19a and 22a, and only traces of the Heck-type formation of unidentified products (Scheme 5).
products were detected (Table 4, entries 1–3 and 6).
Four aryl bromides have been reacted with (E)-3-
With 3-bromonitrobenzene or 1-bromonaphthalene, thiophen-2-yl-1-p-tolylpropenone (Scheme 6). The ar-
the arylated furans 20a and 21a were obtained in 86% ylation took place selectively at C-5 of thiophene. The
and 83% selectivities, respectively (Table 4, entries 4 use of only 0.5 mol% catalyst led to a complete con-
and 5). Again, the phosphine-free Pd
ACHTUNGRTEN(NNUG OAc)2/KOAc version of the aryl bromides and the desired com-
system with electron-deficient aryl bromides appears pounds 37a–40a were obtained in good yields.
to be the best catalyst to prevent the Heck-type reac-
tion to the profit of C-5 arylation.
The use of a furan bearing a trisubstituted alkene
led only to the direct arylation products (Scheme 7).
The reaction is not limited to the direct arylation of The Heck reaction with similar trisubstituted alkenes
furans. Three thiophenes bearing electron-deficient al- is known to be very challenging due to a slow inser-
À
kenes have also been successfully arylated (Scheme 4 tion of such congested alkenes into the Ar Pd
and Scheme 5 and Table 5). Methyl (E)-3-thiophen-2- bonds.[17] A wide range of aryl bromides has been em-
yl acrylate was arylated at carbon 5 of thiophene with ployed, and in all cases, using only 0.1 mol%
very high regioselectivities and yields (Table 5). More- Pd
over, the reaction proceeded using only 0.1 mol% carbon 5 of furan was observed. Moreover, from the
Pd(OAc)2 as the catalyst. Thus, alkenyl-furans and (E)-3-furan-2-yl-2-methylpropenal, the (E)-3-(5-aryl-
ACHTUNGRTEN(NUNG OAc)2 as the catalyst, a regioselective arylation at
ACHTUNGTRENNUNG
thiophenes react similarly towards direct arylation at furan-2-yl)-2-methylpropenals 41–60 were obtained
C-5 in the presence of phosphine-free catalyst. A without isomerisation of the alkenyl bond. It should
range of electron-deficient aryl bromides was success- be noted that with this reactant, the coupling with the
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Table 5. Palladium-catalysed direct coupling of methyl (E)-
electron-rich 4-bromoanisole also proceeded nicely to
give only the arylated furan at C-5 47a in 83% yield.
Thus, the trisubstituted alkene itself disfavours the
Heck-type reaction. This property should be used to
prevent the Heck type reaction with electron-rich aryl
bromides.
3-thiophen-2-yl acrylate with aryl bromides (Scheme 4).[a]
Entry Ratio Major product
Yield of a
a:b
[%]
1
2
3
4
5
98:2
98:2
99:1
98:2
91:9
80
81
79
77
70
Conclusions
We have shown that the PdACHTNUGRTENUNG(OAc)2/KOAc catalyst
system without any phosphine ligand, promotes the
direct arylation of heteroaromatics and inhibits the
Heck reaction with 1,2-disubstituted alkenes. The
nature of the base was found to be crucial to control
the selectivity in favour of the arylation. This reaction
allows the synthesis in one step of a wide variety of 5-
arylated five-membered heteroarenes bearing enone,
enal or acrylates at carbon 2. These couplings can be
performed using low catalyst loadings (0.5–0.1 mol%)
of a commercially available, air-stable and phosphine-
free catalyst. A wide range of functions such as acetyl,
formyl, ester, nitro, trifluoromethyl, fluoro or nitrile
on the aryl bromide is tolerated. It should be noted
6
7
8
9
98:2
90:10
94:6
98:2
77
68
68
84
that a variety of new bisACTHNUTRGNEU(GN hetero)aryl derivatives have
been prepared, indicating that this procedure provides
a convenient access to compounds which cannot be
very easily synthesised using more classical coupling
methods. Finally, due to environmental considera-
tions, the advantage of such an inert wastes procedure
(formation of acetic acid and potassium bromide)
should become increasingly important for industrial
processes.
Experimental Section
10
98:2
81[b]
General Remarks
All reactions were run under argon in Schlenk tubes using
vacuum lines. DMAc analytical grade was not distilled
before use. Potassium acetate (99%) was used. Commercial
aryl halides and heteroarene derivatives were used without
11
12
97:3
97:3
78[b]
73[c]
1
purification. H and 13C NMR spectra were recorded with a
Bruker 300 or 500 MHz spectrometer in CDCl3 solutions.
Chemical shifts are reported in ppm relative to CDCl3 (7.25
1
for H NMR and 77.0 for 13C NMR). Flash chromatography
was performed on silica gel (230–400 mesh).
13
98:2
83[d]
General Procedure for Coupling Reactions
In a typical experiment, the aryl bromide (1 mmol), hetero-
aryl derivative (2 mmol), base (2 mmol) and [Pd] (see
Tables) were dissolved in DMAc (3 mL) under an argon at-
mosphere. The reaction mixture was stirred at 130–1508C
(see Tables) for 17–46 h. Then, the solvent was evaporated
and the isomeric products were separated by silica gel
column chromatography.
[a]
Conditions: PdACHTNUTRGNE(NUG OAc)2 (0.001 equiv.), aryl bromide
(1 equiv.), methyl (E)-3-thiophen-2-yl acrylate (2 equiv.),
AcOK (2 equiv.), DMAc, 17 h, 1308C.
[b]
[c]
[d]
Pd
Pd
Pd
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
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Phosphine-Free Palladium Catalytic System for the Selective Direct Arylation of Furans or Thiophenes
Scheme 6.
Scheme 7.
4-{5-[(E)-3-Oxobut-1-enyl]-furan-2-yl}-benzonitrile (1a):
From 4-bromobenzonitrile (0.182 g, 1 mmol), (E)-4-furan-2-
ylbut-3-en-2-one (0.272 g, 2 mmol) and AcOK (0.196 g,
2 mmol) at 1308C in DMAc (3 mL) for 17 h in the presence
Ethyl
4-{5-[(E)-3-oxobut-1-enyl]-furan-2-yl}-benzoate
(2a): From ethyl 4-bromobenzoate (0.229 g, 1 mmol), (E)-4-
furan-2-ylbut-3-en-2-one (0.272 g, 2 mmol) and AcOK
(0.196 g, 2 mmol) at 1308C in DMAc (3 mL) for 17 h in the
of Pd
G
presence of PdACHTNGUTERNNU(G OAc)2 (0.22 mg, 0.001 mmol) product 2a was
tained; yield: 0.176 g (74%).
obtained; yield: 0.148 g (52%).
(E)-4-(1-Furan-2-yl-3-oxobut-1-enyl)-benzonitrile
(1b):
(E)-4-[5-(4-Nitrophenyl)-furan-2-yl]-but-3-en-2-one (3a):
From 4-bromonitrobenzene (0.202 g, 1 mmol), (E)-4-furan-
2-ylbut-3-en-2-one (0.272 g, 2 mmol) and AcOK (0.196 g,
2 mmol) at 1308C in DMAc (3 mL) for 17 h in the presence
From 4-bromobenzonitrile (0.182 g, 1 mmol), (E)-4-furan-2-
ylbut-3-en-2-one (0.272 g, 2 mmol) and KF (0.116 g, 2 mmol)
at 1308C in DMAc (3 mL) for 17 h in the presence of PdCl-
A
E
of PdClACTHGUNTRENN(UG C3H5)ACHTUNGTRENN(UNG dppb) (6.1 mg, 0.01 mmol) product 3a was
yield: 0.095 g (40%).
obtained; yield: 0.193 g (75%).
4-(1-Furan-2-yl-3-oxobutyl)-benzonitrile (1c): From 4-bro-
mobenzonitrile (0.182 g, 1 mmol), (E)-4-furan-2-ylbut-3-en-
2-one (0.272 g, 2 mmol) and (n-Bu)3N (0.740 g, 4 mmol) at
1508C in DMAc (3 mL) for 17 h in the presence of PdCl-
(E)-4-[5-(3-Acetylphenyl)-furan-2-yl]-but-3-en-2-one (4a):
From 3-bromoacetophenone (0.199 g, 1 mmol), (E)-4-furan-
2-ylbut-3-en-2-one (0.272 g, 2 mmol) and AcOK (0.196 g,
2 mmol) at 1308C in DMAc (3 mL) for 17 h in the presence
A
E
of PdACTHNGUETRNU(NG OAc)2 (0.22 mg, 0.001 mmol) product 4a was ob-
tained; yield: 0.112 g (47%).
tained; yield: (0.130 g (51%).
Adv. Synth. Catal. 2011, 353, 2749 – 2760
ꢁ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
2755

Lu Chen et al.
FULL PAPERS
(E)-4-[5-(3-Nitrophenyl)-furan-2-yl]-but-3-en-2-one (5a):
From 3-bromonitrobenzene (0.202 g, 1 mmol), (E)-4-furan-
2-ylbut-3-en-2-one (0.272 g, 2 mmol) and AcOK (0.196 g,
2 mmol) at 1308C in DMAc (3 mL) for 17 h in the presence
of PdACHTUNGTRENNUNG(OAc)2 (0.22 mg, 0.001 mmol) product 5a was ob-
tained; yield: 0.188 g (73%).
3-{5-[(E)-3-Oxobut-1-enyl]-furan-2-yl}-benzonitrile (6a):
From 3-bromobenzonitrile (0.182 g, 1 mmol), (E)-4-furan-2-
ylbut-3-en-2-one (0.272 g, 2 mmol) and AcOK (0.196 g,
2 mmol) at 1308C in DMAc (3 mL) for 17 h in the presence
of PdACHTUNGTRENNUNG(OAc)2 (1.1 mg, 0.005 mmol) product 6a was obtained;
yield: 0.116 g (40%).
2-{5-[(E)-3-Oxobut-1-enyl]-furan-2-yl}-benzonitrile (7a):
From 2-bromobenzonitrile (0.182 g, 1 mmol), (E)-4-furan-2-
ylbut-3-en-2-one (0.272 g, 2 mmol) and AcOK (0.196 g,
2 mmol) at 1308C in DMAc (3 mL) for 17 h in the presence
of PdACHTUNGTRENNUNG(OAc)2 (0.22 mg, 0.001 mmol) product 7a was ob-
tained; yield: 0.168 g (71%).
(E)-4-Furan-2-yl-4-(4-methoxyphenyl)-but-3-en-2-one
(8b): From 4-bromoanisole (0.187 g, 1 mmol), (E)-4-furan-2-
ylbut-3-en-2-one (0.272 g, 2 mmol) and AcOK (0.196 g,
2 mmol) at 1308C in DMAc (3 mL) for 17 h in the presence
of PdACHTUNGTRENNUNG(OAc)2 (0.22 mg, 0.001 mmol) product 8b was ob-
tained; yield: 0.060 g (25%). The formation of Heck-type Z
2-{5-[(E)-3-Oxopropenyl]-furan-2-yl}-benzonitrile (15a):
From 2-bromobenzonitrile (0.182 g, 1 mmol), (E)-3-furan-2-
ylpropenal (0.244 g, 2 mmol) and AcOK (0.196 g, 2 mmol)
at 1308C in DMAc (3 mL) for 17 h in the presence of
PdClACHTUNTRGENNUG(C3H5)ACHTUGNTREN(NNGU dppb) (6.1 mg, 0.01 mmol) product 15a was ob-
tained; yield: 0.163 g (73%).
(E)-3-Furan-2-yl-3-(4-methoxyphenyl)-propenal
(16b):
From 4-bromoanisole (0.187 g, 1 mmol), (E)-3-furan-2-ylpro-
penal (0.244 g, 2 mmol) and NaHCO3 (0.168 g, 2 mmol) at
1308C in DMAc (3 mL) for 17 h in the presence of
Pd
ACHTUNGRTEN(NUNG OAc)2 (0.22 mg, 0.001 mmol) product 16b was obtained;
yield: 0.93 g (41%).
Methyl
(E)-3-[5-(4-cyanophenyl)-furan-2-yl]-acrylate
(17a): From 4-bromobenzonitrile (0.182 g, 1 mmol), methyl
(E)-3-furan-2-yl acrylate (0.304 g, 2 mmol) and AcOK
(0.196 g, 2 mmol) at 1508C in DMAc (3 mL) for 17 h in the
presence of Pd
ACHTUNGRTENN(UNG OAc)2 (1.1 mg, 0.005 mmol) product 17a was
obtained; yield: 0.205 g (81%).
Methyl
(E)-3-[5-(4-formylphenyl)-furan-2-yl]-acrylate
(18a): From 4-bromobenzaldehyde (0.185 g, 1 mmol),
methyl (E)-3-furan-2-yl acrylate (0.304 g, 2 mmol) and
AcOK (0.196 g, 2 mmol) at 1508C in DMAc (3 mL) for 17 h
in the presence of PdACHTNUGTRNEUNG(OAc)2 (1.1 mg, 0.005 mmol) product
18a was obtained; yield: 0.172 g (67%).
Methyl (E)-3-[5-(4-nitrophenyl)-furan-2-yl]-acrylate (19a):
From 4-bromonitrobenzene (0.202 g, 1 mmol), methyl (E)-3-
furan-2-yl acrylate (0.304 g, 2 mmol) and AcOK (0.196 g,
2 mmol) at 1508C in DMAc (3 mL) for 17 h in the presence
of PdACTHNUTRGNE(UNG OAc)2 (1.1 mg, 0.005 mmol) product 19a was ob-
tained; yield: 0.224 g (82%).
Methyl (E)-3-[5-(3-nitrophenyl)-furan-2-yl]-acrylate (20a):
From 3-bromonitrobenzene (0.202 g, 1 mmol), methyl (E)-3-
furan-2-yl acrylate (0.304 g, 2 mmol) and AcOK (0.196 g,
2 mmol) at 1508C in DMAc (3 mL) for 17 h in the presence
of PdACTHNUTRGNE(UNG OAc)2 (1.1 mg, 0.005 mmol) product 20a was ob-
tained; yield: 0.178 g (65%).
Methyl (E)-3-(5-naphthalen-2-ylfuran-2-yl)-acrylate (21a):
From 2-bromonaphthalene (0.207 g, 1 mmol), methyl (E)-3-
furan-2-yl acrylate (0.304 g, 2 mmol) and AcOK (0.196 g,
2 mmol) at 1508C in DMAc (3 mL) for 17 h in the presence
isomer was also observed.
4-{5-[(E)-3-Oxopropenyl]-furan-2-yl}-benzonitrile
(9a):
From 4-bromobenzonitrile (0.182 g, 1 mmol), (E)-3-furan-2-
ylpropenal (0.244 g, 2 mmol) and AcOK (0.196 g, 2 mmol)
at 1308C in DMAc (3 mL) for 17 h in the presence of
PdACHTUNGTRENNUNG(OAc)2 (0.22 mg, 0.001 mmol) product 9a was obtained;
yield: 0.143 g (64%).
4-{5-[(E)-3-Oxopropenyl]-furan-2-yl}-benzaldehyde (10a):
From 4-bromobenzaldehyde (0.185 g, 1 mmol), (E)-3-furan-
2-ylpropenal (0.244 g, 2 mmol) and AcOK (0.196 g, 2 mmol)
at 1308C in DMAc (3 mL) for 17 h in the presence of
PdACHTUNGTRENNUNG(OAc)2 (0.22 mg, 0.001 mmol) product 10a was obtained;
yield: 0.154 g (68%).
(E)-3-[5-(4-Nitrophenyl)-furan-2-yl]-propenal (11a): From
4-bromonitrobenzene (0.202 g, 1 mmol), (E)-3-furan-2-ylpro-
penal (0.244 g, 2 mmol) and AcOK (0.196 g, 2 mmol) at
1308C in DMAc (3 mL) for 17 h in the presence of Pd-
ACHTUNGTRENNUNG(OAc)2 (0.22 mg, 0.001 mmol) product 11a was obtained;
yield: 0.180 g (74%).
3-{5-[(E)-3-Oxopropenyl]-furan-2-yl}-benzonitrile (12a):
From 3-bromobenzonitrile (0.182 g, 1 mmol), (E)-3-furan-2-
ylpropenal (0.244 g, 2 mmol) and AcOK (0.196 g, 2 mmol)
at 1308C in DMAc (3 mL) for 17 h in the presence of
PdACHTUNGTRENNUNG(OAc)2 (0.22 mg, 0.001 mmol) product 12a was obtained;
yield: 0.147 g (66%).
of Pd
ACHTUNGRTENN(UNG OAc)2 (1.1 mg, 0.005 mmol) product 21a was ob-
tained; yield: (0.172 g (62%).
Methyl
(E)-3-[5-(2-cyanophenyl)-furan-2-yl]-acrylate
(22a): From 2-bromobenzonitrile (0.182 g, 1 mmol), methyl
(E)-3-furan-2-yl acrylate (0.304 g, 2 mmol) and AcOK
(0.196 g, 2 mmol) at 1508C in DMAc (3 mL) for 17 h in the
presence of PdACHTNUTRGNEUNG(OAc)2 (1.1 mg, 0.005 mmol) product 22a was
obtained; yield: (66%).
Methyl (E)-3-[5-(4-cyanophenyl)-thiophen-2-yl]-acrylate
(23a): From 4-bromobenzonitrile (0.182 g, 1 mmol), methyl
(E)-3-thiophen-2-yl acrylate (0.336 g, 2 mmol) and AcOK
(0.196 g, 2 mmol) at 1308C in DMAc (3 mL) for 17 h in the
presence of PdACTHNUTRGNEUNG(OAc)2 (0.22 mg, 0.001 mmol) product 23a
was obtained; yield: 0.215 g (80%).
(E)-3-[5-(3-Acetylphenyl)-furan-2-yl]-propenal
(13a):
From 3-bromoacetophenone (0.199 g, 1 mmol), (E)-3-furan-
2-ylpropenal (0.244 g, 2 mmol) and AcOK (0.196 g, 2 mmol)
at 1308C in DMAc (3 mL) for 17 h in the presence of
PdACHTUNGTRENNUNG(OAc)2 (0.22 mg, 0.001 mmol) product 13a was obtained;
yield: (0.125 g (52%).
(E)-3-[5-(3-Nitrophenyl)-furan-2-yl]-propenal (14a): From
3-bromonitrobenzene (0.202 g, 1 mmol), (E)-3-furan-2-ylpro-
penal (0.244 g, 2 mmol) and AcOK (0.196 g, 2 mmol) at
1308C in DMAc (3 mL) for 17 h in the presence of
Methyl (E)-3-[5-(4-formylphenyl)-thiophen-2-yl]-acrylate
(24a): From 4-bromobenzaldehyde (0.185 g, 1 mmol),
methyl (E)-3-thiophen-2-yl acrylate (0.336 g, 2 mmol) and
AcOK (0.196 g, 2 mmol) at 1308C in DMAc (3 mL) for 17 h
in the presence of Pd
ACHTUNGERTN(NUNG OAc)2 (0.22 mg, 0.001 mmol) product
24a was obtained; yield: 0.220 g (81%).
Pd
ACHTUNGTRENNUNG(OAc)2 (0.22 mg, 0.001 mmol) product 14a was obtained;
Methyl
(E)-3-[5-(4-nitrophenyl)-thiophen-2-yl]-acrylate
yield: 0.170 g (70%).
(25a): From 4-bromonitrobenzene (0.202 g, 1 mmol), methyl
2756
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ꢁ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2011, 353, 2749 – 2760

Phosphine-Free Palladium Catalytic System for the Selective Direct Arylation of Furans or Thiophenes
(E)-3-thiophen-2-yl acrylate (0.336 g, 2 mmol) and AcOK
(0.196 g, 2 mmol) at 1308C in DMAc (3 mL) for 17 h in the
presence of PdACHTUNGTRENNUNG(OAc)2 (0.22 mg, 0.001 mmol) product 25a
Methyl (E)-3-(5-isoquinolin-4-yl-thiophen-2-yl)-acrylate
(35a): From 4-bromoisoquinoline (0.208 g, 1 mmol), methyl
(E)-3-thiophen-2-yl acrylate (0.336 g, 2 mmol) and AcOK
(0.196 g, 2 mmol) at 1508C in DMAc (3 mL) for 46 h in the
was obtained; yield: 0.228 g (79%).
Methyl (E)-3-[5-(4-trifluoromethylphenyl)-thiophen-2-yl]-
acrylate (26a): From the reaction of 4-trifluoromethylbro-
mobenzene (0.225 g, 1 mmol), methyl (E)-3-thiophen-2-yl
acrylate (0.336 g, 2 mmol) and AcOK (0.196 g, 2 mmol) at
1308C in DMAc (3 mL) for 17 h in the presence of
presence of PdACHTNGUTERNNU(G OAc)2 (1.1 mg, 0.005 mmol) product 35a was
obtained; yield: 0.245 g (83%).
2-[5-((E)-3-Oxobut-1-enyl)-thiophen-2-yl]-benzonitrile
(36a): From 2-bromobenzonitrile (0.182 g, 1 mmol), (E)-4-
thien-2-ylbut-3-en-2-one (0.304 g, 2 mmol) and AcOK
(0.196 g, 2 mmol) at 1308C in DMAc (3 mL) for 17 h in the
PdACHTUNGTRENNUNG(OAc)2 (0.22 mg, 0.001 mmol) product 26a was obtained;
yiield: (0.240 g (77%).
presence of PdACHTNGUTERNNU(G OAc)2 (0.22 mg, 0.001 mmol) product 36a
Methyl (E)-3-[5-(4-chlorophenyl)-thiophen-2-yl]-acrylate
(27a): The reaction of 4-chlorobromobenzene (0.191 g,
1 mmol), methyl (E)-3-thiophen-2-yl acrylate (0.336 g,
2 mmol) and AcOK (0.196 g, 2 mmol) at 1308C in DMAc
was obtained; yield: 0.147 g (58%).
(E)-4-[5-(3-Oxo-3-p-tolylpropenyl)-thiophen-2-yl]-benzal-
dehyde (37a): From 4-bromobenzaldehyde (0.185 g,
1 mmol), (E)-3-thiophen-2-yl-1-p-tolylpropenone (0.256 g,
2 mmol) and AcOK (0.196 g, 2 mmol) at 1508C in DMAc
(3 mL) for 17 h in the presence of PdACTHNUTRGENUG(N OAc)2 (1.1 mg,
0.005 mmol) product 27a was obtained; yield: 0.195 g
(70%).
Methyl (E)-3-[5-(3-cyanophenyl)-thiophen-2-yl]-acrylate
(28a): From 3-bromobenzonitrile (0.182 g, 1 mmol), methyl
(E)-3-thiophen-2-yl acrylate (0.336 g, 2 mmol) and AcOK
(0.196 g, 2 mmol) at 1308C in DMAc (3 mL) for 17 h in the
(3 mL) for 17 h in the presence of PdACTHNGURETNNU(G OAc)2 (1.1 mg,
0.005 mmol) product 37a was obtained; yield: 0.226 g
(68%).
(E)-3-[5-(3-Oxo-3-p-tolylpropenyl)-thiophen-2-yl]-benzo-
nitrile (38a): From 3-bromobenzonitrile (0.182 g, 1 mmol),
(E)-3-thiophen-2-yl-1-p-tolylpropenone (0.256 g, 2 mmol)
and AcOK (0.196 g, 2 mmol) at 1508C in DMAc (3 mL) for
presence of PdACHTUNGTRENNUNG(OAc)2 (0.22 mg, 0.001 mmol) product 28a
was obtained; yield: 0.207 g (77%).
17 h in the presence of PdACTHUNGTRENNU(G OAc)2 (1.1 mg, 0.005 mmol)
Methyl (E)-3-[5-(3-formylphenyl)-thiophen-2-yl]-acrylate
(29a):From 3-bromobenzaldehyde (0.185 g, 1 mmol), methyl
(E)-3-thiophen-2-yl acrylate (0.336 g, 2 mmol) and AcOK
(0.196 g, 2 mmol) at 1308C in DMAc (3 mL) for 17 h in the
product 38a was obtained; yield: 0.253 g (77%).
(E)-2-[5-(3-Oxo-3-p-tolylpropenyl)-thiophen-2-yl]-benzo-
nitrile (39a): From 2-bromobenzonitrile (0.182 g, 1 mmol),
(E)-3-thiophen-2-yl-1-p-tolylpropenone (0.256 g, 2 mmol)
and AcOK (0.196 g, 2 mmol) at 1508C in DMAc (3 mL) for
presence of PdACHTUNGTRENNUNG(OAc)2 (0.22 mg, 0.001 mmol) product 29a
was obtained; yield: 0.185 g (68%).
17 h in the presence of PdACTHUNGTRENNU(G OAc)2 (1.1 mg, 0.005 mmol)
Methyl (E)-3-[5-(3-chlorophenyl)-thiophen-2-yl]-acrylate
(30a): The reaction of 3-chlorobromobenzene (0.191 g,
1 mmol), methyl (E)-3-thiophen-2-yl acrylate (0.336 g,
2 mmol) and AcOK (0.196 g, 2 mmol) at 1308C in DMAc
product 39a was obtained; yield: 0.247 g (75%).
(E)-3-(5-Pyridin-3-ylthiophen-2-yl)-1-p-tolylpropenone
(40a): From 3-bromopyridine (0.158 g, 1 mmol), (E)-3-thio-
phen-2-yl-1-p-tolylpropenone (0.256 g, 2 mmol) and AcOK
(0.196 g, 2 mmol) at 1508C in DMAc (3 mL) for 17 h in the
(3 mL) for 17 h in the presence of PdACTHNUTRGENUG(N OAc)2 (1.1 mg,
0.005 mmol) product 30a was obtained; yield: 0.189 g
(68%).
presence of PdACHTNGUTERNNU(G OAc)2 (1.1 mg, 0.005 mmol) product 40a was
obtained; yield: 0.213 g (70%).
Methyl (E)-3-[5-(2-cyanophenyl)-thiophen-2-yl]-acrylate
(31a): From 2-bromobenzonitrile (0.182 g, 1 mmol), methyl
(E)-3-thiophen-2-yl acrylate (0.336 g, 2 mmol) and AcOK
(0.196 g, 2 mmol) at 1308C in DMAc (3 mL) for 17 h in the
(E)-4-[5-(2-Methyl-3-oxopropenyl)-furan-2-yl]-benzoni-
trile (41a): From 4-bromobenzonitrile (0.182 g, 1 mmol),
(E)-3-furan-2-yl-2-methylpropenal (0.272 g, 2 mmol) and
AcOK (0.196 g, 2 mmol) at 1308C in DMAc (3 mL) for 17 h
presence of Pd
G
in the presence of PdACTHNGUTERNNU(G OAc)2 (0.22 mg, 0.001 mmol) product
was obtained; yield: 0.226 g (84%).
41a was obtained; yield: 0.206 g (87%).
Methyl (E)-3-(5-naphthalen-1-yl-thiophen-2-yl)-acrylate
(32a): From 1-bromonaphthalene (0.207 g, 1 mmol), methyl
(E)-3-thiophen-2-yl acrylate (0.336 g, 2 mmol) and AcOK
(0.196 g, 2 mmol) at 1508C in DMAc (3 mL) for 27 h in the
(E)-4-[5-(2-Methyl-3-oxopropenyl)-furan-2-yl]-benzalde-
hyde (42a): From 4-bromobenzaldehyde (0.185 g, 1 mmol),
(E)-3-furan-2-yl-2-methylpropenal (0.272 g, 2 mmol) and
AcOK (0.196 g, 2 mmol) at 1308C in DMAc (3 mL) for 17 h
presence of Pd
G
in the presence of PdACTHNGUTERNNU(G OAc)2 (0.22 mg, 0.001 mmol) product
obtained; yield: 0.238 g (81%).
42a was obtained; yield: 0.216 g (90%).
Methyl (E)-3-(5-pyridin-3-ylthiophen-2-yl)-acrylate (33a):
From 3-bromopyridine (0.158 g, 1 mmol), methyl (E)-3-thio-
phen-2-yl acrylate (0.336 g, 2 mmol) and AcOK (0.196 g,
2 mmol) at 1508C in DMAc (3 mL) for 27 h in the presence
Ethyl (E)-4-[5-(2-methyl-3-oxopropenyl)-furan-2-yl]-ben-
zoate (43a): From ethyl 4-bromobenzoate (0.229 g, 1 mmol),
(E)-3-furan-2-yl-2-methylpropenal (0.272 g, 2 mmol) and
AcOK (0.196 g, 2 mmol) at 1308C in DMAc (3 mL) for 17 h
of Pd
G
in the presence of PdACTHNGUTERNNU(G OAc)2 (0.22 mg, 0.001 mmol) product
tained; yield: 0.191 g (78%).
43a was obtained; yield: 0.259 g (91%).
Methyl
(E)-3-(5-quinolin-3-ylthiophen-2-yl)-acrylate
(E)-2-Methyl-3-[5-(4-nitrophenyl)-furan-2-yl]-propenal
(44a): From 4-bromonitrobenzene (0.202 g, 1 mmol), (E)-3-
furan-2-yl-2-methylpropenal (0.272 g, 2 mmol) and AcOK
(0.196 g, 2 mmol) at 1308C in DMAc (3 mL) for 17 h in the
(34a): From 3-bromoquinoline (0.208 g, 1 mmol), methyl
(E)-3-thiophen-2-yl acrylate (0.336 g, 2 mmol) and AcOK
(0.196 g, 2 mmol) at 1508C in DMAc (3 mL) for 41 h in the
presence of Pd
(OAc)2 (1.1 mg, 0.005 mmol) product 34a was
presence of PdCATHUNGTREN(NNUG OAc)2 (0.22 mg, 0.001 mmol) product 44a
obtained; yield: 0.215 g (73%).
was obtained; yield: 0.211 g (82%).
Adv. Synth. Catal. 2011, 353, 2749 – 2760
ꢁ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
2757

Lu Chen et al.
FULL PAPERS
(E)-3-[5-(4-Fluorophenyl)-furan-2-yl]-2-methylpropenal
(45a): From 4-bromofluorobenzene (0.175 g, 1 mmol), (E)-3-
furan-2-yl-2-methylpropenal (0.272 g, 2 mmol) and AcOK
(0.196 g, 2 mmol) at 1308C in DMAc (3 mL) for 17 h in the
presence of PdACHTUNGTRENNUNG(OAc)2 (0.22 mg, 0.001 mmol) product 45a
was obtained; yield: 0.189 g (82%).
(E)-3-[5-(4-Chlorophenyl)-furan-2-yl]-2-methylpropenal
(46a): From 4-chlorobromobenzene (0.191 g, 1 mmol), (E)-
3-furan-2-yl-2-methylpropenal (0.272 g, 2 mmol) and AcOK
(0.196 g, 2 mmol) at 1308C in DMAc (3 mL) for 17 h in the
presence of PdACHTUNGTRENNUNG(OAc)2 (0.22 mg, 0.001 mmol) product 46a
was obtained; yield: 0.222 g (90%).
(E)-3-[5-(4-Methoxyphenyl)-furan-2-yl]-2-methylpropenal
(47a): From 4-bromoanisole (0.187 g, 1 mmol), (E)-3-furan-
2-yl-2-methylpropenal (0.272 g, 2 mmol) and AcOK (0.196 g,
2 mmol) at 1308C in DMAc (3 mL) for 17 h in the presence
of PdACHTUNGTRENNUNG(OAc)2 (0.22 mg, 0.001 mmol) product 47a was ob-
tained; yield: 0.201 g (83%).
(E)-3-[5-(2-Methyl-3-oxopropenyl)-furan-2-yl]-benzoni-
trile (48a): From 3-bromobenzonitrile (0.182 g, 1 mmol),
(E)-3-furan-2-yl-2-methylpropenal (0.272 g, 2 mmol) and
AcOK (0.196 g, 2 mmol) at 1308C in DMAc (3 mL) for 17 h
in the presence of PdACHTNUGTRNEUNG(OAc)2 (0.22 mg, 0.001 mmol) product
48a was obtained; yield: 0.209 g (88%).
(E)-3-[5-(6-Methoxynaphthalen-2-yl)-furan-2-yl]-2-meth-
ylpropenal (55a): From 2-bromo-6-methoxynaphthalene
(0.237 g,
(0.272 g, 2 mmol) and AcOK (0.196 g, 2 mmol) at 1308C in
DMAc (3 mL) for 17 h in the presence of Pd(OAc)2
1 mmol),
(E)-3-furan-2-yl-2-methylpropenal
ACHTUNGTRENNUNG
(0.22 mg, 0.001 mmol) product 55a was obtained; yield:
0.263 g (90%).
(E)-2-[5-(2-Methyl-3-oxopropenyl)-furan-2-yl]-benzoni-
trile (56a): From 2-bromobenzonitrile (0.182 g, 1 mmol),
(E)-3-furan-2-yl-2-methylpropenal (0.272 g, 2 mmol) and
AcOK (0.196 g, 2 mmol) at 1308C in DMAc (3 mL) for 17 h
in the presence of PdACHTNUGTRNEUNG(OAc)2 (0.22 mg, 0.001 mmol) product
56a was obtained; yield: (0.197 g (83%).
(E)-2-Methyl-3-(5-naphthalen-1-ylfuran-2-yl)-propenal
(57a): From 1-bromonaphthalene (0.207 g, 1 mmol), (E)-3-
furan-2-yl-2-methylpropenal (0.272 g, 2 mmol) and AcOK
(0.196 g, 2 mmol) at 1308C in DMAc (3 mL) for 17 h in the
presence of PdACTHNUTRGNEUNG(OAc)2 (0.22 mg, 0.001 mmol) product 57a
was obtained; yield: 0.223 g (85%).
(E)-2-Methyl-3-(5-pyridin-3-ylfuran-2-yl)-propenal (58a):
From 3-bromopyridine (0.158 g, 1 mmol), (E)-3-furan-2-yl-2-
methylpropenal (0.272 g, 2 mmol) and AcOK (0.196 g,
2 mmol) at 1308C in DMAc (3 mL) for 17 h in the presence
of PdACTHNUTRGNE(UNG OAc)2 (0.22 mg, 0.001 mmol) product 58a was ob-
tained; yield: 0.166 g (78%).
(E)-2-Methyl-3-(5-quinolin-3-ylfuran-2-yl)-propenal (59a):
From 3-bromoquinoline (0.208 g, 1 mmol), (E)-3-furan-2-yl-
2-methylpropenal (0.272 g, 2 mmol) and AcOK (0.196 g,
2 mmol) at 1308C in DMAc (3 mL) for 17 h in the presence
(E)-3-[5-(3-Acetylphenyl)-furan-2-yl]-2-methylpropenal
(49a): From 3-bromoacetophenone (0.199 g, 1 mmol), (E)-3-
furan-2-yl-2-methylpropenal (0.272 g, 2 mmol) and AcOK
(0.196 g, 2 mmol) at 1308C in DMAc (3 mL) for 17 h in the
presence of PdACHTUNGTRENNUNG(OAc)2 (0.22 mg, 0.001 mmol) product 49a
was obtained; yield: 0.231 g (91%).
of PdACTHNUTRGNE(UNG OAc)2 (0.22 mg, 0.001 mmol) product 59a was ob-
tained; yield: 0.224 g (85%).
(E)-3-[5-(2-Methyl-3-oxopropenyl)-furan-2-yl]-benzalde-
hyde (50a): From 3-bromobenzaldehyde (0.185 g, 1 mmol),
(E)-3-furan-2-yl-2-methylpropenal (0.272 g, 2 mmol) and
AcOK (0.196 g, 2 mmol) at 1308C in DMAc (3 mL) for 17 h
(E)-3-(5-Isoquinolin-5-ylfuran-2-yl)-2-methylpropenal
(60a): From 4-bromoisoquinoline (0.208 g, 1 mmol), (E)-3-
furan-2-yl-2-methylpropenal (0.272 g, 2 mmol) and AcOK
(0.196 g, 2 mmol) at 1308C in DMAc (3 mL) for 17 h in the
in the presence of PdACHTNUGTRNEUNG(OAc)2 (0.22 mg, 0.001 mmol) product
presence of PdACTHNUTRGNEUNG(OAc)2 (0.22 mg, 0.001 mmol) product 60a
50a was obtained; yield: 0.144 g (60%).
was obtained; yield: 0.226 g (86%).
(E)-2-Methyl-3-[5-(3-nitrophenyl)-furan-2-yl]-propenal
(51a): From 3-bromonitrobenzene (0.202 g, 1 mmol), (E)-3-
furan-2-yl-2-methylpropenal (0.272 g, 2 mmol) and AcOK
(0.196 g, 2 mmol) at 1308C in DMAc (3 mL) for 17 h in the
Acknowledgements
presence of PdACHTUNGTRENNUNG(OAc)2 (0.22 mg, 0.001 mmol) product 51a
L. C. is grateful to the Chinese Scholarship Council for a
PhD grant. J. R. is grateful to “Ministꢀre de la Recherche”
for a grant. We thank the Centre National de la Recherche
Scientifique and “Rennes Metropole” for providing financial
support.
was obtained; yield: 0.234 g (91%).
(E)-3-[5-(3-Chlorophenyl)-furan-2-yl]-2-methylpropenal
(52a): The reaction of 3-chlorobromobenzene (0.191 g,
1 mmol),
2 mmol) and AcOK (0.196 g, 2 mmol) at 1308C in DMAc
(3 mL) for 17 h in the presence of Pd(OAc)2 (0.22 mg,
(E)-3-furan-2-yl-2-methylpropenal
(0.272 g,
AHCTUNGTRENNUNG
0.001 mmol) product 52a was obtained; yield: 0.222 g
(90%).
(E)-3-[5-(3-Fluorophenyl)-furan-2-yl]-2-methylpropenal
(53a): From 3-bromofluorobenzene (0.175 g, 1 mmol), (E)-3-
furan-2-yl-2-methylpropenal (0.272 g, 2 mmol) and AcOK
(0.196 g, 2 mmol) at 1508C in DMAc (3 mL) for 17 h in the
presence of PdACHTUNGTRENNUNG(OAc)2 (1.1 mg, 0.005 mmol) product 53a was
obtained; yield: 0.163 g (71%).
(E)-2-Methyl-3-(5-naphthalen-2-ylfuran-2-yl)-propenal
(54a): From 2-bromonaphthalene (0.207 g, 1 mmol), (E)-3-
furan-2-yl-2-methylpropenal (0.272 g, 2 mmol) and AcOK
(0.196 g, 2 mmol) at 1308C in DMAc (3 mL) for 17 h in the
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2758
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Adv. Synth. Catal. 2011, 353, 2749 – 2760

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Adv. Synth. Catal. 2011, 353, 2749 – 2760