Palladium-Catalysed Direct Polyarylation of Pyrrole Derivatives

Article abstract of DOI:10.1002/cctc.201200521

The palladium-catalysed direct polyarylation of 1-methylpyrrole and 1-phenylpyrrole was studied. As the C2 and C5 positions of pyrroles are more reactive for C-H bond functionalisation than the C3 and C4 positions, the formation of 2,5-diarylpyrroles was

Full text of DOI:10.1002/cctc.201200521

CHEMCATCHEM
FULL PAPERS
DOI: 10.1002/cctc.201200521
Palladium-Catalysed Direct Polyarylation of Pyrrole
Derivatives
Liqin Zhao, Christian Bruneau, and Henri Doucet*[a]
The palladium-catalysed direct polyarylation of 1-methylpyrrole
and 1-phenylpyrrole was studied. As the C2 and C5 positions
of pyrroles are more reactive for CÀH bond functionalisation
than the C3 and C4 positions, the formation of 2,5-diarylpyr-
roles was found to proceed selectively in the presence of
3 equiv. of a variety of aryl bromides. The sequential C2 aryla-
tion followed by C5 arylation to prepare non-symmetrically
substituted 2,5-diarylpyrroles was also studied. For the synthe-
sis of such pyrroles, higher yields were obtained for the cou-
plings with electron-deficient aryl bromides. The tetraarylation
of 1-methylpyrrole was also achieved. From 4 equiv. of 3,5-bis-
(trifluoromethyl)bromobenzene, the 2,3,4,5-tetraarylated pyr-
role was obtained in good yield.
Introduction
The classical palladium-catalysed reactions such as Stille,
Suzuki or Negishi couplings allow the formation of a wide vari-
ety of polyaryls.[1] However, for these couplings a prior synthe-
sis of (poly)organometallic derivatives is required, which might
be difficult, especially with heteroarenes. Moreover, these reac-
tions provide a stoichiometric amount of metallic side prod-
ucts, from which undesired contamination could be harmful
for pharmaceutical, agrochemical and related biological appli-
cations. As early as 1985, Ohta and co-workers reported that
the arylations of several heteroaromatics,[2] including pyrroles,
with aryl halides proceed in moderate to good yields through
CÀH bond activation,[3,4] using Pd(PPh3)4 as the catalyst. Since
these results, the palladium-catalysed direct arylation of pyr-
roles with aryl halides has proved to be a very powerful
method for the synthesis of a wide variety of arylated
pyrroles.[5–9]
Figure 1. Regioselectivity of the arylation of pyrroles.
ported an elegant regioselective 2,5-diarylation of an N-pyridyl-
pyrrole and also of an N-pyrimidylpyrrole using a ruthenium
catalyst.[11] For these reactions, the pyridyl or pyrimidyl sub-
stituent on the nitrogen atom acted as a directing group to
favour the regioselective arylations at both C2 and C5 posi-
tions of the pyrrole. However, the Suzuki, Stille and Negishi
coupling reactions remain the most classic methods to prepare
polyarylated pyrrole derivatives.[12] For example, in 2009
Dauban and co-workers described the 2,5-diarylation of a 2,5-
dibromopyrrole through Suzuki coupling.[12d]
In palladium-catalysed direct arylation of pyrroles, the most
reactive positions are generally the carbons C2 and C5, where-
as the positions C3 and C4 display
(Figure 1).[3g]
a poor reactivity
In most cases, intramolecular arylations[5] or intermolecular
C5-arylations of C2-substituted pyrroles have been reported.[7,8]
The monoarylation at C2 of some non-substituted 1-alkylpyr-
roles or 1-arylpyrroles has also been described.[9] On the other
hand, to our knowledge only one example of a palladium-cata-
lysed diarylation of a pyrrole has been reported.[10] From 1-
methylpyrrole and 4-(trifluoromethyl)phenyliodide, Shibahara
and co-workers obtained the 2,5-diarylated 1-methylpyrrole in
79% yield by using Pd(1,10-phenanthroline)2(PF6)2 (5 mol%) as
the catalyst. Notably, Ackermann and co-workers have also re-
As only one example of a palladium-catalysed direct diaryla-
tion of pyrrole derivatives has been reported, the discovery of
a procedure allowing a more general access to symmetrically
or non-symmetrically substituted 2,5-diarylpyrroles is desirable.
Recently we have reported that the reaction of pyrroles with
various substituents at C2 with aryl bromides using KOAc as
the base, N,N-dimethylacetamide (DMAc) as the solvent and
Pd(OAc)2 as the catalyst led to the C5 arylated heteroaromatics
in high yield.[13] We have also reported a few examples of mon-
oarylation of 1-methylpyrrole.
[a] L. Zhao, C. Bruneau, Dr. H. Doucet
Institut Sciences Chimiques de Rennes, UMR 6226
CNRS-Universitꢀ de Rennes 1. “Organomꢀtalliques: Matꢀriaux et Catalyse”
Campus de Beaulieu, 35042 Rennes (France)
Fax: (+33)0223236939
Herein, starting from 1-methylpyrrole or 1-phenylpyrrole as
the reactants, we report on a catalytic system based on palladi-
um which gives access to 1) symmetrically 2,5-diarylated pyr-
E-mail: henri.doucet@univ-rennes1.fr
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ChemCatChem 2013, 5, 255 – 262 255

CHEMCATCHEM
FULL PAPERS
www.chemcatchem.org
roles with a set of aryl bromides, 2) 2,3,4,5-tetraarylated pyr-
roles and 3) unsymmetrically 2,5-diarylated pyrroles through
sequential C2 catalytic arylation followed by C5 catalytic
arylation.
42% of 1b was obtained if 2.5 equivalents of 4-bromoaceto-
phenone were employed with this catalyst (Table 1, entry 3).
Then, we employed a larger excess of 4-bromoacetophenone.
With 3 equivalents of this aryl bromide, a yield of 46% of 1b
was obtained, whereas the use of 4 equivalents led to a lower
yield of 30% (Table 1, entries 4 and 5).
Results and Discussion
Then, we examined the scope of this procedure using para-,
meta- or ortho-substituted aryl bromides and also heteroaryl
bromides (Scheme 2, Table 2). The electron-deficient para-sub-
Firstly, we considered the reaction of 1-methylpyrrole with 4-
bromoacetophenone to form the 2,5-diarylated pyrrole 1b
(Scheme 1). We observed that from 4-bromoacetophenone
(2.2 equiv.) and 1-methylpyrrole (1 equiv.) with KOAc (4 equiv.)
Scheme 2. Palladium-catalysed 2,5-diarylation of 1-methylpyrrole.
stituted aryl bromides, 4-bromobenzaldehyde, 4-bromopropio-
phenone, 4-bromobenzophenone, 4-bromonitrobenzene or 4-
bromobenzonitrile reacted with 1-methylpyrrole to give the ex-
pected products 2–6 in 58–69% yields (Table 2, entries 1–5). A
high yield of 81% of 7 was obtained with ethyl 4-bromoben-
zoate (Table 2, entry 6). From 4-chlorobromobenzene, 9 was
obtained in 62% yield (Table 2, entry 8). In the course of this
reaction no cleavage of the CÀCl bond was observed, which
allows for further transformations. Surprisingly, even the elec-
tron-rich aryl bromide, 4-tert-butylbromobenzene was success-
fully coupled with 1-methylpyrrole to give 10 in 52% yield
(Table 2, entry 9). A set of meta-substituted aryl bromides was
also employed. The best yields were obtained from 3-bromoa-
cetophenone and 3-bromonitrobenzene to give 11 and 12 in
78 and 80% yields, respectively (Table 2, entries 10 and 11).
Lower yields of 13–15 were obtained in the presence of 3-bro-
mobenzonitrile, 3-chlorobromobenzene and 3-bromotoluene,
respectively (Table 2, entries 12–14). 1- and 2-bromonaphtha-
lenes also gave the desired products 16 and 17 in 65 and 68%
yields, respectively (Table 2, entries 15 and 16). We also em-
ployed heteroaryl bromides. The first attempt to prepare 18
from 3-bromopyridine led to a mixture of di- and triarylated
pyrroles, and 18 was isolated in only 41% yield (Table 2,
entry 17). However, the use of only 2.3 equivalents instead of
3 equivalents of 3-bromopyridine allowed us to obtain 18 in
a higher yield of 62% (Table 2, entry 18). A more selective reac-
tion was observed in the presence of 5-bromopyrimidine,
which gave 19 in 71% yield (Table 2, entry 19).
Scheme 1. Palladium-catalysed 2,5-diarylation of 1-methylpyrrole with
4-bromoacetophenone.
as the base, DMAc as the solvent and a catalyst loading of
only 0.1 mol% Pd(OAc)2, the 2,5-diarylated pyrrole 1b was ob-
tained only in low yield because of the formation of a mixture
of mono- and diarylated pyrroles 1a and 1b (Table 1, entry 1).
The use of a higher Pd(OAc)2 load (1 mol%, Table 1, entry 2)
did not improve the yield. These results reveal that the con-
centration of active Pd species is relatively similar across these
two different concentrations of Pd(OAc)2. In this ligand-free
procedure with relatively high palladium concentrations, so-
called “palladium black” forms rapidly, which is inactive in such
catalyses. Consequently, the conversions of aryl bromides and
the yields of coupling products are not increased by a higher
catalyst loading.
Table 1. Influence of the reaction conditions on the palladium-catalysed
direct 2,5-diarylation of 1-methylpyrrole with 4-bromoacetophenone
(Scheme 1).[a]
Entry
Catalyst
[mol%]
4-bromoacetophenone
[equiv.]
Yield of 1b
[%]
1
2
3
4
5
Pd(OAc)2 (0.1)
Pd(OAc)2 (1)
PdCl(C3H5)(dppb) (1)
PdCl(C3H5)(dppb) (1)
PdCl(C3H5)(dppb) (1)
2.2
2.5
2.5
3
27
21
42
46
30
4
Then, arylation reactions of 1-phenylpyrrole with aryl bro-
mides were examined (Scheme 3, Table 3). With this reactant,
again only the C2 and C5 diarylated pyrroles 20–24 were iso-
lated; however, in lower yield than with 1-methylpyrrole. First-
ly, we studied the reactivity of two para-substituted aryl bro-
mides. In the presence of 4-chlorobromobenzene or 4-bromo-
toluene, the products 20 and 21 were obtained in 35 and 33%
yields, respectively (Table 3, entries 1 and 2). Higher yields of
54 and 52% were obtained in the presence of the meta-substi-
tuted aryl bromides, 3-bromobenzonitrile or 3-chlorobromo-
[a] 1-methylpyrrole (1 equiv.), KOAc (4 equiv.), DMAc, T=1508C, t=16 h,
isolated yields of 1b.
Therefore, we employed PdCl(C3H5)(dppb) [dppb=1,4-bis(di-
phenylphosphino)butane] 1 mol% as the catalyst, which forms
palladium black less rapidly. Moreover, we have recently dem-
onstrated that this catalyst was among the best catalyst for
the direct arylation of some thiophenes.[4b] A higher yield of
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ChemCatChem 2013, 5, 255 – 262 256

CHEMCATCHEM
FULL PAPERS
www.chemcatchem.org
Table 2. Scope of the palladium-catalysed direct 2,5-diarylation of
1-methylpyrrole (Scheme 2).[a]
Entry Aryl bromide
Product
Yield
[%]
1
2
2
3
69
60
Scheme 3. Palladium-catalysed 2,5-diarylation of 1-phenylpyrrole.
Table 3. Scope of the palladium-catalysed direct 2,5-diarylation of
1-phenylpyrrole (Scheme 3).[a]
3
4
62
Entry
Aryl bromide
Product
Yield
[%]
4
5
5
6
67
58
1
2
3
4
5
20
21
22
23
24
35
33
54
52
51
6
7
81
7
8
9
8
9
69
62
10 52
11 78
[a] PdCl(C3H5)(dppb) (0.01 equiv.), aryl bromide (3 equiv.), 1-phenylpyrrole
(1 equiv.), KOAc (4 equiv.), DMAc, T=1508C, t=16 h, isolated yields.
10
The reactivity of 3,5-bis(trifluoromethyl)bromobenzene with
1-methylpyrrole was unusual compared to that of the other
aryl bromides. The reaction of 3 equivalents of this aryl bro-
mide with 1-methylpyrrole led to a mixture of di-, tri- and even
some tetraarylated pyrroles according to GC–MS analysis.
Therefore, to obtain the 2,3,4,5-tetraarylated pyrrole 25 more
selectively, we employed 4 equivalents of this aryl bromide.
Under these conditions, 25 was the major product with 85%
selectivity and 62% yield (Scheme 4).
11
12
12 80
13 61
13
14
15
14 63
15 62
16 65
16
17 68
41
17
18
18
62[b]
19
19 71
Scheme 4. Palladium-catalysed tetraarylation of 1-methylpyrrole.
[a] PdCl(C3H5)(dppb) (0.01 equiv.), aryl bromide (3 equiv.), 1-methylpyrrole
(1 equiv.), KOAc (4 equiv.), DMAc, T=1508C, t=16 h, isolated yields. [b] 3-
bromopyridine (2.3 equiv.).
Then, we studied the sequential C2 arylation followed by
a C5 different arylation of pyrroles to prepare non-symmetrical
2,5-diarylpyrroles (Scheme 5, Table 4). The yields of the palladi-
um-catalysed C5 direct arylations of 2-arylpyrroles were as-
sumed to depend on the electronic properties of the aryl sub-
benzene, respectively (Table 3, entries 3 and 4). Finally, from 5-
bromopyrimidine, 24 was formed in 51% yield.
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ChemCatChem 2013, 5, 255 – 262 257

CHEMCATCHEM
FULL PAPERS
www.chemcatchem.org
such phosphine-free conditions allows efficient direct monoar-
ylation of some pyrrole derivatives.[13]
For the first reaction step (Scheme 5, top), the electron-defi-
cient aryl bromides, 4-bromobenzonitrile and 4-bromonitro-
benzene, gave the C2 monoarylated products 26, 30 and 31
very selectively. The C2,C5 diarylated pyrroles were only pro-
duced as traces. A high yield of 29 was also obtained from 2-
bromonaphthalene. On the other hand, the reactions with 4-
bromotoluene and 4-tert-butylbromobenzene surprisingly gave
mixtures of mono- and diarylated pyrroles (mono-/diarylation
ratio of 75:25), although we employed a 1:4 ratio of aryl bro-
mide and pyrrole derivative. The second arylation step of pyr-
roles appeared to be favoured by the presence of electron-do-
nating groups on the aryl substituent of 2-arylpyrroles.
For the C5 arylation step, we observed that the reaction of
4-bromotoluene with 26 gave 33 in 52% yield, whereas the re-
action of 4-bromobenzonitrile with 27 led to 33 in 71% yield
(Table 4, entries 1 and 2). Product 34 was also obtained in
much higher yield by coupling of 4-bromobenzonitrile with 28
than by using 4-tert-butylbromobenzene and 26 (Table 4, en-
tries 3 and 4). On the other hand, very similar yields in 35 were
obtained by both reaction pathways (Table 4, entries 5 and 6).
For the synthesis of 36 and 37, again the best yields were ob-
tained by using the most electron-deficient aryl bromide in the
second step (Table 4, entries 7–
Scheme 5. Palladium-catalysed sequential 2,5-diarylation of 1-methylpyrrole.
stituents both on the pyrrole and the aryl bromide. Therefore,
we initially compared the reaction yields by using the two pos-
sible combinations of starting materials to prepare a specific
2,5-diarylpyrrole. For both steps we employed 0.5 mol%
Pd(OAc)2 as the catalyst because we previously observed that
10). In summary, for the synthe-
sis of non-symmetrical 2,5-diary-
Table 4. Scope of the palladium-catalysed direct sequential 2,5-diarylation of 1-methyl- or 1-phenyl-2-arylpyr-
lpyrroles, high yields were ob-
tained for both reaction steps
with electron-deficient aryl bro-
mides. On the other hand, with
roles (Scheme 5).[a]
Entry
Pyrrole
Aryl bromide
Product
Yield
[%]
electron-rich
aryl
bromides,
1
2
3
4
5
6
7
8
9
26
27
26
28
26
29
30
28
31
33
33
34
34
35
35
36
36
37
52
71
32
74
87
90
42
80
55
moderate yields were obtained
because of the formation of
some 2,5-diarylpyrroles in the re-
action with 1-methylpyrrole or
the poor reactivity of the aryl
bromides in the C5 arylation of
some 2-arylpyrroles.
Finally, the 4,4’-diheteroaryla-
tion of 4,4’-dibromobiphenyl
was studied (Scheme 6). From 1-
methylpyrrole (3 equiv.) and 4,4’-
dibromobiphenyl (1 equiv.) in
the presence of 1 mol% PdCl-
(C3H5)(dppb), the desired prod-
uct 38 was produced in 81%
yield (Scheme 6).
Conclusions
We have demonstrated that the
palladium-catalysed direct diary-
lation at C2 and C5 of 1-methyl-
pyrrole or 1-phenylpyrrole using
10
32
37
86
[a] Pd(OAc)2 (0.005 equiv.), aryl bromide (1.5 equiv.), 1-methyl- or 1-phenyl-2-arylpyrrole (1 equiv.), KOAc
(2 equiv.), DMAc, T=1508C, t=16 h, isolated yields.
PdCl(C3H5)(dppb)
[dppb=1,4-
bis(diphenylphosphino)butane]
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ChemCatChem 2013, 5, 255 – 262 258

CHEMCATCHEM
FULL PAPERS
www.chemcatchem.org
26.6 ppm. Elemental analysis: calcd (%) for C21H19NO2 (317.38): C
79.47, H 6.03, N 4.41; found: C 79.69, H 6.09, N 4.31.
2,5-Bis(4-formylphenyl)-1-methylpyrrole 2: From 4-bromobenzal-
dehyde (0.555 g, 3 mmol) and 1-methylpyrrole (0.081 g, 1 mmol), 2
was obtained in 69% (0.200 g) yield. 1H NMR (400 MHz, CDCl3,
258C): d=9.96 (s, 2H), 7.87 (d, J=7.0 Hz, 4H), 7.57 (d, J=7.0 Hz,
4H), 6.43 (s, 2H), 3.63 ppm (s, 3H). 13C NMR (100 MHz, CDCl3,
258C): d=191.6, 138.7, 137.6, 134.7, 130.1, 128.6, 111.4, 35.2 ppm.
Elemental analysis: calcd (%) for C19H15NO2 (289.33): C 78.87, H
5.23, N 4.84; found: C 78.96, H 5.35, N 4.89.
Scheme 6. Palladium-catalysed arylation of 1-methylpyrrole with
4,4’-dibromobiphenyl.
2,5-Bis(4-propionylphenyl)-1-methylpyrrole 3: From 4-bromopro-
1 mol% as the catalyst and KOAc as the base proceeds with
electron-poor and some electron-rich aryl bromides. A variety
of substituents on the aryl bromide such as ester, acetyl,
formyl, propionyl, benzoyl, nitro, nitrile, chloro, fluoro or tert-
butyl is tolerated. The sequential C2 arylation of 1-methylpyr-
role or 1-phenylpyrrole followed by C5 arylation reveals that
electron-deficient aryl bromides should be employed prefera-
bly. Notably, from 3,5-bis(trifluoromethyl)bromobenzene and 1-
methylpyrrole, the 2,3,4,5-tetrarylated product was formed in
good yield. To our knowledge, this is the first example of a cat-
alysed direct tetraarylation of a pyrrole. Moreover, these aryla-
tions were performed with only 0.5–1 mol% of air-stable cata-
lysts. The major by-products of these reactions are a base asso-
ciated to HBr, and the method does not require the initial
preparation of a requisite (poly)organometallic compound,
thus reducing the number of reaction steps. For these reasons,
this process gives an economically viable and environmentally
attractive access to polyarylated pyrrole derivatives.
piophenone (0.639 g, 3 mmol) and 1-methylpyrrole (0.081 g,
1 mmol), 3 was obtained in 60% (0.207 g) yield. H NMR (400 MHz,
1
CDCl3, 258C): d=7.96 (d, J=7.0 Hz, 4H), 7.50 (d, J=7.0 Hz, 4H),
6.38 (s, 2H), 3.61 (s, 3H), 2.96 (q, J=7.5 Hz, 4H), 1.19 ppm (t, J=
7.5 Hz, 6H). 13C NMR (100 MHz, CDCl3, 258C): d=200.2, 137.4,
137.3, 135.1, 128.4, 128.3, 110.6, 34.9, 31.7, 8.3 ppm. Elemental anal-
ysis: calcd (%) for C23H23NO2 (345.43): C 79.97, H 6.71, N 4.05;
found: C 80.11, H 6.64, N 3.89.
{4-[5-(4-Benzoyl-phenyl)-1-methylpyrrol-2-yl]-phenyl}-phenyl-
methanone 4: From 4-bromobenzophenone (0.783 g, 3 mmol) and
1-methylpyrrole (0.081 g, 1 mmol),
4 was obtained in 62%
(0.273 g) yield. 1H NMR (400 MHz, CDCl3, 258C): d=7.83 (d, J=
7.6 Hz, 4H), 7.78 (d, J=7.6 Hz, 4H), 7.60–7.50 (m, 6H), 7.44 (t, J=
7.6 Hz, 4H), 6.42 (s, 2H), 3.67 ppm (s, 3H). 13C NMR (100 MHz,
CDCl3, 258C): d=196.1, 137.7, 137.3, 137.1, 135.7, 132.4, 130.6,
130.0, 128.3, 128.0, 110.7, 35.0 ppm. Elemental analysis: calcd (%)
for C31H23NO2 (441.52): C 84.33, H 5.25, 3.17; found: C 84.21, H 5.01,
N 3.28.
2,5-Bis(4-nitrophenyl)-1-methylpyrrole 5:[15] From 4-bromonitro-
benzene (0.606 g, 3 mmol) and 1-methylpyrrole (0.081 g, 1 mmol),
5 was obtained in 67% (0.216 g) yield.
2,5-Bis(4-cyanophenyl)-1-methylpyrrole 6:[5g] From 4-bromoben-
zonitrile (0.546 g, 3 mmol) and 1-methylpyrrole (0.081 g, 1 mmol),
6 was obtained in 58% (0.164 g) yield.
Experimental Section
DMAc (N,N-dimethylacetamide) (99%) was purchased from Acros.
KOAc (99%), [Pd(C3H5)Cl]2 (56.5%) and dppb [1,4-bis(diphenylphos-
phino)butane] (98%) were purchased from Alfa Aesar. These com-
pounds were not purified before use.
2,5-Bis(ethyl 4-benzoate)-1-methylpyrrole 7: From ethyl 4-bromo-
benzoate (0.687 g, 3 mmol) and 1-methylpyrrole (0.081 g, 1 mmol),
7 was obtained in 81% (0.305 g) yield. 1H NMR (400 MHz, CDCl3,
258C): d=8.03 (d, J=7.0 Hz, 4H), 7.47 (d, J=7.0 Hz, 4H), 6.37 (s,
2H), 4.33 (q, J=7.5 Hz, 4H), 3.59 (s, 3H), 1.34 ppm (t, J=7.5 Hz,
6H). 13C NMR (100 MHz, CDCl3, 258C): d=166.4, 137.3, 137.2, 129.8,
128.7, 128.1, 110.4, 61.0, 34.9, 14.4 ppm. Elemental analysis: calcd
(%) for C23H23NO4 (377.43): C 73.19, H 6.14, N 3.71; found: C 73.04,
H 6.10, N 3.88.
Preparation of the PdCl(C3H5)(dppb) catalyst:[14] 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 dppb (426 mg, 1 mmol). Anhydrous dichlorome-
thane (10 mL) was added and the solution was stirred at RT for
20 min. The solvent was removed in vacuum. The yellow powder
was used without purification. 31P NMR (81 MHz, CDCl3): d=
19.3 ppm (s).
2,5-Bis(4-fluorophenyl)-1-methylpyrrole 8: From 4-fluorobromo-
benzene (0.525 g, 3 mmol) and 1-methylpyrrole (0.081 g, 1 mmol),
8 was obtained in 69% (0.186 g) yield. 1H NMR (400 MHz, CDCl3,
258C): d=7.34 (dd, J=8.6, 5.4 Hz, 4H), 7.04 (t, J=8.6 Hz, 4H), 6.19
(s, 2H), 3.47 ppm (s, 3H). 13C NMR (100 MHz, CDCl3, 258C): d=
162.0 (d, J=246.8 Hz), 135.7, 130.4 (d, J=8.0 Hz), 129.6, 115.4 (d,
J=21.5 Hz), 108.6, 33.9 ppm. Elemental analysis: calcd (%) for
C17H13F2N (269.29): C 75.82, H 4.87, N 5.20; found: C 75.90, H 4.74,
N 5.39.
General procedure for syntheses of 1–24: As a typical experi-
ment, reaction of the aryl bromide (3 mmol), 1-methylpyrrole
(0.081 g, 1 mmol) or 1-phenylpyrrole (0.143 g, 1 mmol), and KOAc
(0.392 g, 4 mmol) at 1508C during 16 h in DMAc (3 mL) in the pres-
ence of PdCl(C3H5)(dppb) (6.1 mg, 0.01 mmol) under argon afford-
ed the corresponding diarylation product after extraction with di-
chloromethane, evaporation and filtration on silica gel.
2,5-Bis(4-acetylphenyl)-1-methylpyrrole 1b: From 4-bromoaceto-
phenone (0.597 g, 3 mmol) and 1-methylpyrrole (0.081 g, 1 mmol),
1 was obtained in 46% (0.146 g) yield. 1H NMR (400 MHz, CDCl3,
258C): d=7.95 (d, J=7.8 Hz, 4H), 7.50 (d, J=7.8 Hz, 4H), 6.39 (s,
2H), 3.61 (s, 3H), 2.56 ppm (s, 6H). 13C NMR (100 MHz, CDCl3,
258C): d=197.5, 137.5, 137.3, 135.3, 128.7, 128.2, 110.7, 35.0,
2,5-Bis(4-chlorophenyl)-1-methylpyrrole 9: From 4-bromochloro-
benzene (0.574 g, 3 mmol) and 1-methylpyrrole (0.081 g, 1 mmol),
9 was obtained in 62% (0.187 g) yield. 1H NMR (400 MHz, CDCl3,
258C): d=7.30 (s, 8H), 6.22 (s, 2H), 3.48 ppm (s, 3H). 13C NMR
(100 MHz, CDCl3, 258C): d=136.1, 132.9, 131.8, 129.9, 128.7, 109.2,
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ChemCatChem 2013, 5, 255 – 262 259

CHEMCATCHEM
FULL PAPERS
www.chemcatchem.org
34.3 ppm. Elemental analysis: calcd (%) for C17H13Cl2N (302.20): C
67.57, H 4.34, N 4.63; found: C 67.47, H 4.30, N 4.50.
sis: calcd (%) for C25H19N (333.43): C 90.06, H 5.74, N 4.20; found: C
90.11, H 5.60, N 4.11.
1-Methyl-2,5-dinaphthalen-1-ylpyrrole 17:[16] From 1-bromonaph-
thalene (0.621 g, 3 mmol) and 1-methylpyrrole (0.081 g, 1 mmol),
17 was obtained in 68% (0.227 g) yield.
2,5-Bis(4-tert-butylphenyl)-1-methylpyrrole 10: From 4-tert-butyl-
bromobenzene (0.639 g, 3 mmol) and 1-methylpyrrole (0.081 g,
1 mmol), 10 was obtained in 52% (0.179 g) yield. 1H NMR
(400 MHz, CDCl3, 258C): d=7.36 (d, J=7.0 Hz, 4H), 7.33 (d, J=
7.0 Hz, 4H), 6.21 (s, 2H), 3.54 (s, 3H), 1.29 ppm (s, 18H). 13C NMR
(100 MHz, CDCl3, 258C): d=149.7, 136.6, 130.8, 128.4, 125.3, 108.3,
34.6, 34.3, 31.4 ppm. Elemental analysis: calcd (%) for C25H31N
(345.52): C 86.90, H 9.04, N 4.05; found: C 86.98, H 9.18, N 4.23.
2,5-Bis(pyridin-3-yl)-1-methylpyrrole 18: From 3-bromopyridine
(0.363 g, 2.3 mmol) and 1-methylpyrrole (0.081 g, 1 mmol), 18 was
obtained in 62% (0.146 g) yield. 1H NMR (400 MHz, CDCl3, 258C):
d=8.69 (s, 2H), 8.50 (d, J=4.9 Hz, 2H), 7.70 (d, J=7.7 Hz, 2H), 7.30
(dd, J=7.7, 4.9 Hz, 2H), 6.34 (s, 2H), 3.56 ppm (s, 3H). 13C NMR
(100 MHz, CDCl3, 258C): d=149.5, 148.2, 135.7, 134.0, 129.1, 123.4,
110.2, 34.1 ppm. Elemental analysis: calcd (%) for C15H13N3 (235.28):
C 76.57, H 5.57, N 17.86; found: C 76.69, H 5.40, N 17.69.
2,5-Bis(3-acetylphenyl)-1-methylpyrrole 11: From 3-bromoaceto-
phenone (0.597 g, 3 mmol) and 1-methylpyrrole (0.081 g, 1 mmol),
1
11 was obtained in 78% (0.247 g) yield. H NMR (400 MHz, CDCl3,
258C): d=7.99 (s, 2H), 7.83 (d, J=7.5 Hz, 2H), 7.60 (d, J=7.5 Hz,
2H), 7.46 (t, J=7.5 Hz, 2H), 6.31 (s, 2H), 3.55 (s, 3H), 2.58 ppm (s,
6H). 13C NMR (100 MHz, CDCl3, 258C): d=198.0, 137.4, 136.4, 133.8,
133.1, 128.9, 128.4, 126.8, 109.5, 34.3, 26.7 ppm. Elemental analysis:
calcd (%) for C21H19NO2 (317.38): C 79.47, H 6.03, N 4.41; found: C
79.35, H 6.11, N 4.65.
2,5-Bis(pyrimidin-5-yl)-1-methylpyrrole 19: From 5-bromopyrimi-
dine (0.477 g, 3 mmol) and 1-methylpyrrole (0.081 g, 1 mmol), 19
was obtained in 71% (0.168 g) yield. 1H NMR (400 MHz, CDCl3,
258C): d=9.12 (s, 2H), 8.80 (s, 4H), 6.44 (s, 2H), 3.60 ppm (s, 3H).
13C NMR (100 MHz, CDCl3, 258C): d=157.2, 155.8, 131.1, 127.1,
111.5, 34.0 ppm. Elemental analysis: calcd (%) for C13H11N5 (237.26):
C 65.81, H 4.67, N 29.52; found: C 65.79, H 4.79, N 29.68.
2,5-Bis(3-nitrophenyl)-1-methylpyrrole 12: From 3-bromonitro-
benzene (0.606 g, 3 mmol) and 1-methylpyrrole (0.081 g, 1 mmol),
1
2,5-Bis(4-chlorophenyl)-1-phenylpyrrole 20: From 4-bromochloro-
12 was obtained in 80% (0.258 g) yield. H NMR (400 MHz, CDCl3,
benzene (0.574 g, 3 mmol) and 1-phenylpyrrole (0.143 g, 1 mmol),
20 was obtained in 35% (0.127 g) yield. H NMR (400 MHz, CDCl3,
258C): d=8.27 (s, 2H), 8.12 (d, J=7.9 Hz, 2H), 7.74 (d, J=7.9 Hz,
2H), 7.55 (t, J=7.5 Hz, 2H), 6.39 (s, 2H), 3.61 ppm (s, 3H). 13C NMR
(100 MHz, CDCl3, 258C): d=148.5, 135.7, 134.5, 134.2, 129.6, 123.1,
121.8, 110.7, 34.5 ppm. Elemental analysis: calcd (%) for C17H13N3O4
(323.30): C 63.15, H 4.05, N 13.00; found: C 63.31, H 4.14, N 12.89.
1
258C): d=7.25–7.15 (m, 5H), 7.07 (d, J=7.9 Hz, 4H), 6.89 (d, J=
7.9 Hz, 4H), 6.39 ppm (s, 2H). 13C NMR (100 MHz, CDCl3, 258C): d=
138.5, 134.9, 132.3, 131.5, 129.8, 129.1, 128.8, 128.2, 127.7,
110.3 ppm. Elemental analysis: calcd (%) for C22H15Cl2N (364.27): C
72.54, H 4.15, N 3.85; found: C 72.39, H 4.07, N 4.02.
2,5-Bis(3-cyanophenyl)-1-methylpyrrole 13: From 3-bromobenzo-
nitrile (0.546 g, 3 mmol) and 1-methylpyrrole (0.081 g, 1 mmol), 13
was obtained in 61% (0.172 g) yield. 1H NMR (400 MHz, CDCl3,
258C): d=7.67 (s, 2H), 7.62 (d, J=7.9 Hz, 2H), 7.52 (d, J=7.9 Hz,
2H), 7.48 (t, J=7.5 Hz, 2H), 6.31 (s, 2H), 3.53 ppm (s, 3H). 13C NMR
(100 MHz, CDCl3, 258C): d=135.6, 134.3, 132.7, 131.8, 130.5, 129.5,
118.6, 113.0, 110.5, 34.4 ppm. Elemental analysis: calcd (%) for
C19H13N3 (283.33): C 80.54, H 4.62, N 14.83; found: C 80.68, H 4.78,
N 14.99.
2,5-Bis(4-methylphenyl)-1-phenylpyrrole 21: From 4-bromoto-
luene (0.513 g, 3 mmol) and 1-phenylpyrrole (0.143 g, 1 mmol), 21
was obtained in 33% (0.107 g) yield. 1H NMR (400 MHz, CDCl3,
258C): d=7.17–7.10 (m, 3H), 7.00–6.92 (m, 2H), 6.90–6.80 (m, 8H),
6.35 (s, 2H), 2.18 ppm (s, 6H). 13C NMR (100 MHz, CDCl3, 258C): d=
139.2, 135.8, 135.7, 130.5, 129.0, 128.7, 128.6, 128.5, 127.1, 109.5,
21.1 ppm. Elemental analysis: calcd (%) for C24H21N (323.43): C
89.12, H 6.54, N 4.33; found: C 89.20, H 6.68, N 4.25.
2,5-Bis(3-chlorophenyl)-1-methylpyrrole 14: From 3-bromochlor-
2,5-Bis(3-cyanophenyl)-1-phenylpyrrole 22: From 3-bromobenzo-
nitrile (0.546 g, 3 mmol) and 1-phenylpyrrole (0.143 g, 1 mmol), 22
was obtained in 54% (0.186 g) yield. 1H NMR (400 MHz, CDCl3,
258C): d=7.40–7.10 (m, 10H), 6.97–6.90 (m, 3H), 6.48 ppm (s, 2H).
13C NMR (100 MHz, CDCl3, 258C): d=137.7, 134.3, 134.0, 132.6,
131.8, 129.9, 129.5, 128.8, 128.6, 128.5, 118.6, 112.4, 111.4 ppm. Ele-
mental analysis: calcd (%) for C24H15N3 (345.40): C 83.46, H 4.38, N
12.17; found: C 83.61, H 4.17, N 12.35.
obenzene (0.574 g, 3 mmol) and 1-methylpyrrole (0.081 g, 1 mmol),
14 was obtained in 63% (0.190 g) yield. H NMR (400 MHz, CDCl3,
1
258C): d=7.36 (s, 2H), 7.30–7.22 (m, 4H), 7.19 (t, J=7.5 Hz, 2H),
6.24 (s, 2H), 3.51 ppm (s, 3H). 13C NMR (100 MHz, CDCl3, 258C): d=
136.0, 135.0, 134.4, 129.8, 128.6, 127.0, 126.7, 109.6, 34.4 ppm. Ele-
mental analysis: calcd (%) for C17H13Cl2N (302.20): C 67.57, H 4.34, N
4.63; found: C 67.69, H 4.48, N 4.82.
2,5-Bis(m-tolyl)-1-methylpyrrole 15: From 3-bromotoluene
(0.513 g, 3 mmol) and 1-methylpyrrole (0.081 g, 1 mmol), 15 was
obtained in 62% (0.162 g) yield. 1H NMR (400 MHz, CDCl3, 258C):
d=7.30–7.15 (m, 6H), 7.05 (d, J=7.8 Hz, 2H), 6.22 (s, 2H), 3.51 (s,
3H), 2.33 ppm (s, 6H). 13C NMR (100 MHz, CDCl3, 258C): d=138.0,
136.9, 133.6, 129.5, 128.3, 127.6, 125.8, 108.6, 34.3, 21.5 ppm. Ele-
mental analysis: calcd (%) for C19H19N (261.36): C 87.31, H 7.33, N
5.36; found: C 87.47, H 7.14, N 5.47.
2,5-Bis(3-chlorophenyl)-1-phenylpyrrole 23: From 3-bromochloro-
benzene (0.574 g, 3 mmol) and 1-phenylpyrrole (0.143 g, 1 mmol),
1
23 was obtained in 52% (0.189 g) yield. H NMR (400 MHz, CDCl3,
258C): d=7.25–7.15 (m, 3H), 7.05–6.90 (m, 8H), 6.77 (d, J=7.9 Hz,
2H), 6.42 ppm (s, 2H). 13C NMR (100 MHz, CDCl3, 258C): d=138.3,
134.8, 134.7, 133.8, 129.1, 129.0, 128.8, 128.5, 127.9, 126.7, 126.4,
110.7 ppm. Elemental analysis: calcd (%) for C22H15Cl2N (364.27): C
72.54, H 4.15, N 3.85; found: C 72.66, H 4.25, N 3.64.
1-Methyl-2,5-dinaphthalen-2-ylpyrrole 16: From 2-bromonaph-
thalene (0.621 g, 3 mmol) and 1-methylpyrrole (0.081 g, 1 mmol),
16 was obtained in 65% (0.216 g) yield. H NMR (400 MHz, CDCl3,
258C): d=7.88 (s, 2H), 7.85–7.80 (m, 6H), 7.60 (d, J=7.8 Hz, 2H),
7.45–7.40 (m, 4H), 6.41 (s, 2H), 3.69 ppm (s, 3H). 13C NMR
(100 MHz, CDCl3, 258C): d=137.3, 133.5, 132.3, 130.9, 128.0, 127.9,
127.7, 127.1, 127.0, 126.4, 125.9, 109.5, 34.7 ppm. Elemental analy-
2,5-Bis(pyrimidin-5-yl)-1-phenylpyrrole 24: From 5-bromopyrimi-
dine (0.477 g, 3 mmol) and 1-phenylpyrrole (0.143 g, 1 mmol), 24
was obtained in 51% (0.152 g) yield. 1H NMR (400 MHz, CDCl3,
258C): d=8.93 (s, 2H), 8.35 (s, 4H), 7.40–7.28 (m, 3H), 7.03 (d, J=
7.8 Hz, 2H), 6.62 ppm (s, 2H). 13C NMR (100 MHz, CDCl3, 258C): d=
156.5, 155.4, 137.0, 130.7, 130.1, 129.3, 128.6, 126.8, 112.1 ppm. Ele-
1
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ChemCatChem 2013, 5, 255 – 262 260

CHEMCATCHEM
FULL PAPERS
www.chemcatchem.org
mental analysis: calcd (%) for C18H13N5 (299.33): C 72.23, H 4.38, N
23.40; found: C 72.31, H 4.24, N 23.19.
tive (1 mmol) and KOAc (0.196 g, 2 mmol) at 1508C during 16 h in
DMAc (3 mL) in the presence of PdOAc)2 (1.12 mg, 0.005 mmol)
under argon afforded the corresponding arylation product after ex-
traction with dichloromethane, evaporation and filtration on silica
gel.
2,3,4,5-Tetrakis-(3,5-bis-trifluoromethylphenyl)-1-methylpyrrole
25: The reaction of 3,5-bis-(trifluoromethyl)bromobenzene (1.172 g,
4 mmol), 1-methylpyrrole (0.081 g, 1 mmol) and KOAc (0.392 g,
4 mmol) at 1508C during 16 h in DMAc (3 mL) in the presence of
PdCl(C3H5)(dppb) (6.1 mg, 0.01 mmol) under argon affords after ex-
traction with dichloromethane, evaporation and filtration on silica
gel the tetraarylation product 25 in 62% (0.576) yield. 1H NMR
(400 MHz, CDCl3, 258C): d=7.84 (s, 2H), 7.11 (s, 4H), 7.56 (s, 2H),
7.26 (s, 4H), 3.46 ppm (s, 3H). 13C NMR (100 MHz, CDCl3, 258C): d=
135.1, 132.7, 132.6 (q, J=33.9 Hz), 131.9 (q, J=33.5 Hz), 131.3,
130.9 (m), 130.2 (m), 122.6 (q, J=272.7 Hz), 122.5 (q, J=272.7 Hz),
122.4 (m), 121.8, 120.5 (m), 33.8 ppm. Elemental analysis: calcd (%)
for C37H15F24N (929.48): C 47.81, H 1.63, N 1.51; found: C 47.99, H
1.97, N 1.36.
4-(1-Methyl-5-p-tolylpyrrol-2-yl)-benzonitrile 33: From 4-bromo-
benzonitrile (0.273 g, 1.5 mmol) and 1-methyl-2-p-tolylpyrrole 27
1
(0.171 g, 1 mmol), 33 was obtained in 71% (0.223 g) yield. H NMR
(400 MHz, CDCl3, 258C): d=7.61 (d, J=7.8 Hz, 2H), 7.49 (d, J=
7.8 Hz, 2H), 7.28 (d, J=7.8 Hz, 2H), 7.18 (d, J=7.8 Hz, 2H), 6.36 (d,
J=3.7 Hz, 1H), 6.24 (d, J=3.7 Hz, 1H), 3.55 (s, 3H), 2.34 ppm (s,
3H). 13C NMR (100 MHz, CDCl3, 258C): d=139.2, 137.9, 137.3, 134.7,
132.3, 130.0, 129.3, 128.8, 128.3, 119.1, 110.8, 109.5, 109.1, 34.6,
21.2 ppm. Elemental analysis: calcd (%) for C19H16N2 (272.34): C
83.79, H 5.92, N 10.29; found: C 83.97, H 5.99, N 10.36.
4-[5-(4-tert-Butylphenyl)-1-methylpyrrol-2-yl]-benzonitrile
34:
General procedure for the synthesis of 26–32: As a typical experi-
ment, the reaction of the aryl bromide (1 mmol), 1-methylpyrrole
(0.324 g, 4 mmol) or 1-phenylpyrrole (0.572 g, 4 mmol), and KOAc
(0.196 g, 2 mmol) at 1508C during 16 h in DMAc (3 mL) in the pres-
ence of Pd(OAc)2 (1.1 mg, 0.005 mmol) under argon afforded the
corresponding arylation product after extraction with dichlorome-
thane, evaporation and filtration on silica gel.
From 4-bromobenzonitrile (0.273 g, 1.5 mmol) and 2-(4-tert-butyl-
phenyl)-1-methylpyrrole 28 (0.213 g, 1 mmol), 34 was obtained in
74% (0.232 g) yield. 1H NMR (400 MHz, CDCl3, 258C): d=7.61 (d,
J=7.8 Hz, 2H), 7.49 (d, J=7.8 Hz, 2H), 7.39 (d, J=7.8 Hz, 2H), 7.32
(d, J=7.8 Hz, 2H), 6.36 (d, J=3.7 Hz, 1H), 6.24 (d, J=3.7 Hz, 1H),
3.56 (s, 3H), 1.29 ppm (s, 9H). 13C NMR (100 MHz, CDCl3, 258C): d=
150.5, 139.2, 137.9, 134.6, 132.3, 130.0, 128.6, 128.2, 125.5, 119.1,
110.8, 109.5, 109.2, 34.7, 31.3 ppm. Elemental analysis: calcd (%) for
C22H22N2 (314.42): C 84.04, H 7.05, N 8.91; found: C 83.89, H 7.18, N
8.67.
4-(1-Methylpyrrol-2-yl)-benzonitrile 26:[13] From 4-bromobenzoni-
trile (0.182 g, 1 mmol) and 1-methylpyrrole (0.324 g, 4 mmol), 26
was obtained in 83% (0.151 g) yield.
1-Methyl-2-p-tolylpyrrole 27:[17] From 4-bromotoluene (0.171 g,
1 mmol) and 1-methylpyrrole (0.324 g, 4 mmol), 27 was obtained
in 66% (0.113 g) yield.
4-(1-Methyl-5-naphthalen-2-ylpyrrol-2-yl)-benzonitrile 35: From
4-bromobenzonitrile (0.273 g, 1.5 mmol) and 1-methyl-2-naphtha-
len-2-ylpyrrole 29 (0.207 g, 1 mmol), 35 was obtained in 90%
(0.277 g) yield. 1H NMR (400 MHz, CDCl3, 258C): d=7.89–7.78 (m,
4H), 7.63 (d, J=7.8 Hz, 2H), 7.55–7.50 (m, 3H), 7.50–7.40 (m, 2H),
6.41 (d, J=3.7 Hz, 1H), 6.39 (d, J=3.7 Hz, 1H), 3.63 ppm (s, 3H).
13C NMR (100 MHz, CDCl3, 258C): d=139.2, 137.8, 135.3, 133.4,
132.5, 132.4, 130.2, 128.4, 128.2, 128.0, 127.7, 127.5, 126.9, 126.6,
126.2, 119.1, 111.1, 110.0, 109.7, 34.9 ppm. Elemental analysis: calcd
(%) for C22H16N2 (308.38): C 85.69, H 5.23, N 9.08; found: C 85.88, H
5.41, 8.98.
2-(4-tert-Butylphenyl)-1-methylpyrrole 28: From 4-tert-butylbro-
mobenzene (0.213 g, 1 mmol) and 1-methylpyrrole (0.324 g,
4 mmol), 28 was obtained in 56% (0.119 g) yield. 1H NMR
(400 MHz, CDCl3, 258C): d=7.33 (d, J=8.3 Hz, 2H), 7.25 (d, J=
8.3 Hz, 2H), 6.61 (s, 1H), 6.15–6.06 (m, 2H), 3.57 (s, 3H), 1.27 ppm
(s, 9H). 13C NMR (100 MHz, CDCl3, 258C): d=149.7, 134.6, 130.5,
128.4, 125.3, 123.3, 108.4, 107.7, 35.1, 34.6, 31.4 ppm. Elemental
analysis: calcd (%) for C15H19N (213.32): C 84.46, H 8.98, N 6.57;
found: C 84.5, H 8.79, N 6.40.
2-(4-tert-Butylphenyl)-1-methyl-5-(4-nitrophenyl)-pyrrole
36:
1-Methyl-2-naphthalen-2-ylpyrrole 29: From 2-bromonaphthalene
(0.207 g, 1 mmol) and 1-methylpyrrole (0.324 g, 4 mmol), 29 was
obtained in 89% (0.184 g) yield. 1H NMR (400 MHz, CDCl3, 258C):
d=8.07–8.00 (m, 4H), 7.77 (d, J=7.8 Hz, 1H), 7.71–7.62 (m, 2H),
6.94 (m, 1H), 6.61 (m, 1H), 6.50 (m, 1H), 3.86 ppm (s, 3H). 13C NMR
(100 MHz, CDCl3, 258C): d=134.6, 133.5, 132.2, 130.8, 128.0, 127.9,
127.7, 127.2, 127.0, 126.4, 125.9, 124.0, 109.2, 108.0, 35.3 ppm. Ele-
mental analysis: calcd (%) for C15H13N (207.27): C 86.92, H 6.32, N
6.76; found: C 86.99, H 6.24, N 6.64.
From 4-bromonitrobenzene (0.303 g, 1.5 mmol) and 2-(4-tert-butyl-
phenyl)-1-methylpyrrole 28 (0.213 g, 1 mmol), 36 was obtained in
80% (0.267 g) yield. 1H NMR (400 MHz, CDCl3, 258C): d=8.18 (d,
J=7.8 Hz, 2H), 7.52 (d, J=7.8 Hz, 2H), 7.39 (d, J=7.8 Hz, 2H), 7.32
(d, J=7.8 Hz, 2H), 6.42 (d, J=3.7 Hz, 1H), 6.26 (d, J=3.7 Hz, 1H),
3.58 (s, 3H), 1.29 ppm (s, 9H). 13C NMR (100 MHz, CDCl3, 258C): d=
150.6, 145.8, 139.9, 139.8, 134.4, 129.8, 128.6, 127.9, 125.5, 124.0,
111.6, 109.5, 34.8, 34.7, 31.3 ppm. Elemental analysis: calcd (%) for
C21H22N2O2 (334.41): C 75.42, H 6.63, N 8.38; found: C 75.58, H 6.54,
N 8.24.
1-Methyl-2-(4-nitrophenyl)-pyrrole 30:[17] From 4-bromonitroben-
zene (0.202 g, 1 mmol) and 1-methylpyrrole (0.324 g, 4 mmol), 30
was obtained in 81% (0.164 g) yield.
4-(1-Phenyl-5-p-tolylpyrrol-2-yl)-benzonitrile 37: From 4-bromo-
benzonitrile (0.273 g, 1.5 mmol) and 1-phenyl-2-p-tolyl-1-pyrrole 32
(0.233 g, 1 mmol), 37 was obtained in 86% (0.287 g) yield. H NMR
4-(1-Phenylpyrrol-2-yl)-benzonitrile 31:[13] From 4-bromobenzoni-
trile (0.182 g, 1 mmol) and 1-phenylpyrrole (0.536 g, 4 mmol), 31
was obtained in 80% (0.195 g) yield.
1
(400 MHz, CDCl3, 258C): d=7.34 (d, J=7.8 Hz, 2H), 7.25–7.15 (m,
3H), 7.02 (d, J=7.8 Hz, 2H), 7.00–6.96 (m, 2H), 6.92 (d, J=7.8 Hz,
2H), 6.86 (d, J=7.8 Hz, 2H), 6.52 (d, J=3.7 Hz, 1H), 6.86 (d, J=
3.7 Hz, 1H), 2.21 ppm (s, 3H). 13C NMR (100 MHz, CDCl3, 258C): d=
138.6, 137.9, 137.7, 136.6, 133.3, 131.7, 129.7, 129.1, 128.8, 128.7,
128.6, 128.2, 127.8, 119.1, 111.9, 110.3, 109.0, 21.1 ppm. Elemental
analysis: calcd (%) for C24H18N2 (334.41): C 86.20, H 5.43, N 8.38;
found: C 86.01, H 5.59, N 8.40.
1-Phenyl-2-p-tolylpyrrole 32:[13] From 4-bromotoluene (0.171 g,
1 mmol) and 1-phenylpyrrole (0.536 g, 4 mmol), 32 was obtained
in 52% (0.121 g) yield.
General procedure for the synthesis of 33–37: As a typical experi-
ment, the reaction of the aryl bromide (1.5 mmol), pyrrole deriva-
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ChemCatChem 2013, 5, 255 – 262 261

CHEMCATCHEM
FULL PAPERS
www.chemcatchem.org
Mitani, A. Mori, Synlett 2006, 3170; e) L. Joucla, F. Popowycz, O. Lozach,
L. Meijer, B. Joseph, Helv. Chim. Acta 2007, 90, 753; f) S. Lage, U. Marti-
nez-Estibalez, N. Sotomayor, E. Lete, Adv. Synth. Catal. 2009, 351, 2460;
g) J. K. Laha, G. D. Cuny, J. Org. Chem. 2011, 76, 8477.
4,4’-Bis(1-methylpyrrol-2-yl)-biphenyl 38: From 4,4’-dibromobi-
phenyl (0.312 g, 1 mmol), 1-methylpyrrole (0.243 g, 3 mmol) and
KOAc (0.392 g, 4 mmol) at 1508C during 16 h in DMAc (3 mL) in
the presence of PdCl(C3H5)(dppb) (6.1 mg, 0.01 mmol), 38 was ob-
[6] For examples of palladium-catalysed direct intermolecular 2- or 5-aryla-
tions of pyrrolyl salts, see: a) L. Filippini, M. Gusmeroli, P. Riva, Tetrahe-
dron Lett. 1992, 33, 1755; b) R. D. Rieth, N. P. Mankad, E. Calimano, J. P.
Sadighi, Org. Lett. 2004, 6, 3981; c) D. L. Swartz, A. L. Odom, Organome-
tallics 2006, 25, 6125.
[7] For examples of palladium-catalysed direct intermolecular 5-arylations
of substituted pyrroles: a) M. Romero, Y. Harrak, J. Basset, L. Ginet, P.
Constans, M. D. Pujol, Tetrahedron 2006, 62, 9010; b) B. B. Tourꢁ, B. S.
Lane, D. Sames, Org. Lett. 2006, 8, 1979; c) X. Wang, D. V. Gribkov, D.
Sames, J. Org. Chem. 2007, 72, 1476; d) B. Liꢁgaut, D. Lapointe, L.
Caron, A. Vlassova, K. Fagnou, J. Org. Chem. 2009, 74, 1826; e) J. J.
Dong, J. Roger, C. Verrier, T. Martin, R. Le Goff, C. Hoarau, H. Doucet,
Green Chem. 2010, 12, 2053; f) O. Renꢁ, K. Fagnou, Adv. Synth. Catal.
2010, 352, 2116; g) N. Laidaoui, J. Roger, A. Miloudi, D. El Abed, H.
Doucet, Eur. J. Org. Chem. 2011, 4373.
1
tained in 81% (0.253 g) yield. H NMR (400 MHz, CDCl3, 258C): d=
7.59 (d, J=8.2 Hz, 4H), 7.42 (d, J=8.2 Hz, 4H), 6.67 (m, 2H), 6.22
(m, 2H), 6.16 (m, 2H), 3.65 ppm (s, 6H). 13C NMR (100 MHz, CDCl3,
258C): d=138.9, 134.2, 132.3, 128.9, 126.9, 123.9, 108.9, 107.9,
35.2 ppm. Elemental analysis: calcd (%) for C22H20N2 (312.41): C
84.58, H 6.45, N 8.97; found: C 84.69, H 6.69, N 8.79.
Acknowledgements
We thank the CNRS and “Rennes Metropole” for providing finan-
cial support. The authors are grateful to the Chinese Scholarship
Council for a grant to L.Z.
[8] For examples of iridium-catalysed direct intermolecular arylations of
pyrroles, see: B. Join, T. Yamamoto, K. Itami, Angew. Chem. 2009, 121,
3698; Angew. Chem. Int. Ed. 2009, 48, 3644.
Keywords: aryl bromides · CÀH activation · direct arylation ·
palladium · pyrroles
[9] For examples of palladium-catalysed direct intermolecular 2-arylations
of non-substituted pyrroles, see: a) Y. Aoyagi, A. Inoue, I. Koizumi, R. Ha-
shimoto, K. Tokunaga, K. Gohma, J. Komatsu, K. Sekine, A. Miyafuji, J.
Kunoh, R. Honma, Y. Akita, A. Ohta, Heterocycles 1992, 33, 257; b) D. T.
Gryko, O. Vakuliuk, D. Gryko, B. Koszarna, J. Org. Chem. 2009, 74, 9517;
c) B. Liꢁgault, I. Petrov, S. I. Gorelsky, K. Fagnou, J. Org. Chem. 2010, 75,
1047; d) F. Jafarpour, S. Rahiminejadan, H. Hazrati, J. Org. Chem. 2010,
75, 3109; e) A. Lazareva, O. Daugulis, J. Org. Chem. 2011, 76, 471; f) C. B.
Bheeter, J. K. Bera, H. Doucet, Tetrahedron Lett. 2012, 53, 509.
[10] For an example of palladium-catalysed direct intermolecular 2,5-diaryla-
tion of a pyrrole, see: F. Shibahara, E. Yamaguchi, T. Murai, Chem.
Commun. 2010, 46, 2471.
[1] a) J. J. Li, G. W. Gribble, Palladium in Heterocyclic Chemistry, Pergamon,
Amsterdam, 2000; b) Handbook of Organopalladium Chemistry for Or-
ganic Synthesis (Ed.: E. Negishi), Wiley, New York, 2002, Part III, p. 213.
[2] a) Y. Akita, A. Inoue, K. Yamamoto, A. Ohta, T. Kurihara, M. Shimizu, Het-
erocycles 1985, 23, 2327; b) A. Ohta, Y. Akita, T. Ohkuwa, M. Chiba, R. Fu-
kunaga, A. Miyafuji, T. Nakata, N. Tani, Y. Aoyagi, Heterocycles 1990, 31,
1951.
[3] a) T. Satoh, M. Miura, Chem. Lett. 2007, 36, 200; b) L.-C. Campeau, D. R.
Stuart, K. Fagnou, Aldrichim. Acta 2007, 40, 35; c) I. V. Seregin, V. Ge-
vorgyan, Chem. Soc. Rev. 2007, 36, 1173; d) B.-J. Li, S.-D. Yang, Z.-J. Shi,
Synlett 2008, 949; e) F. Bellina, R. Rossi, Tetrahedron 2009, 65, 10269;
f) L. Ackermann, R. Vicente, A. Kapdi, Angew. Chem. 2009, 121, 9976;
Angew. Chem. Int. Ed. 2009, 48, 9792; g) J. Roger, A. L. Gottumukkala, H.
Doucet, ChemCatChem 2010, 2, 20; h) C.-L. Sun, B.-J. Li, Z.-J. Shi, Chem.
Commun. 2010, 46, 677; i) C. Fischmeister, H. Doucet, Green Chem. 2011,
13, 741.
[4] For selected recent examples of palladium-catalysed direct arylations of
heteroaromatics from our laboratory, see: a) R. V. Smaliy, M. Beaupꢁrin,
H. Cattey, P. Meunier, J.-C. Hierso, J. Roger, H. Doucet, Y. Coppel, Orga-
nometallics 2009, 28, 3152; b) F. Derridj, J. Roger, S. Djebbar, H. Doucet,
Org. Lett. 2010, 12, 4320; c) J. Roger, F. Pozgan, H. Doucet, Adv. Synth.
Catal. 2010, 352, 696; d) L. Chen, J. Roger, C. Bruneau, P. H. Dixneuf, H.
Doucet, Chem. Commun. 2011, 47, 1872; e) K. Beydoun, H. Doucet,
ChemSusChem 2011, 4, 526; f) K. Si Larbi, H. Y. Fu, N. Laidaoui, K. Bey-
doun, A. Miloudi, D. El Abed, S. Djabbar, H. Doucet, ChemCatChem
2012, 4, 815.
[5] For examples of palladium-catalysed intramolecular direct 2- or 5-aryla-
tions of pyrroles, see: a) T. Honma, K. Hayashi, T. Aoyama, N. Hashimoto,
T. Machida, K. Fukasawa, T. Iwama, C. Ikeura, M. Ikuta, I. Suzuki-Takaha-
shi, Y. Iwasawa, T. Hayama, S. Nishimura, H. Morishima, J. Med. Chem.
2001, 44, 4615; b) C. A. Olsen, N. Parera, F. Albericio, M. Alvarez, Tetrahe-
dron Lett. 2005, 46, 2041; c) D. Pla, A. Marchal, C. O. Olsen, F. Albericio,
M. Alvarez, J. Org. Chem. 2005, 70, 8231; d) N. Arai, M. Takahashi, M.
[11] For examples of ruthenium-catalysed direct intermolecular 2,5-diaryla-
tions of pyrroles, see: L. Ackermann, A. V. Lygin, Org. Lett. 2011, 13,
3332.
[12] For examples of palladium-catalysed 2,5-diarylations of pyrroles via
Suzuki, Negishi or Stille couplings, see: a) A. Dhanabalan, J. Knol, J. C.
Hummelen, R. A. J. Janssen, Synth. Met. 2001, 119, 519; b) H. Gour, S.
Jain, S. K. Arora, N. Sinha, Bioorg. Med. Chem. Lett. 2005, 15, 3592; c) T. T.
Dang, R. Ahmad, T. T. Dang, H. Reinke, P. Langer, Tetrahedron Lett. 2008,
49, 1698; d) F. Beaumard, P. Dauban, R. H. Dodd, Org. Lett. 2009, 11,
1801; e) S.-M. T. Toguem, O. Fatunsin, A. Villinger, P. Langer, Tetrahedron
Lett. 2011, 52, 3732.
[13] J. Roger, H. Doucet, Adv. Synth. Catal. 2009, 351, 1977.
[14] T. Cantat, E. Gꢁnin, C. Giroud, G. Meyer, A. Jutand, J. Organomet. Chem.
2003, 687, 365.
[15] R. K. Arafa, R. Brun, K. A. Werbovetz, F. A. Tanious, W. D. Wilson, D. W.
Boykin, Heterocycl. Commun. 2004, 10, 423.
[16] Y. V. Shurukhin, N. A. Klyuev, I. I. Grandberg, Zh. Org. Khim. 1985, 21,
2057.
[17] F. Bilodeau, M.-C. Brochu, N. Guimond, K. H. Thesen, P. Forgione, J. Org.
Chem. 2010, 75, 1550.
Received: July 31, 2012
Published online on November 19, 2012
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ChemCatChem 2013, 5, 255 – 262 262