Regioselective C-2 or C-5 direct arylation of pyrroles with aryl bromides using a ligand-free palladium Catalyst

Article abstract of DOI:10.1002/adsc.200900196

A simple and atom-economical procedure for the regioselective C-2 or C-S arylation of pyrroles via a C-H bond activation is reported. Only 0.5-0.01 mol% of commercially available and air-stable ligand-free palladium(II) acetate [Pd(OAc)₂] was e

Full text of DOI:10.1002/adsc.200900196

FULL PAPERS
DOI: 10.1002/adsc.200900196
Regioselective C-2 or C-5 Direct Arylation of Pyrroles with Aryl
Bromides using a Ligand-Free Palladium Catalyst
Julien Rogera 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)-(0)2-2323-6939; phone: (+33)-(0)2-2323-6384; e-mail: henri.doucet@univ-rennes1.fr
Received: March 27, 2009; Published online: July 11, 2009
Abstract: A simple and atom-economical procedure This environmentally attractive procedure has also
for the regioselective C-2 or C-5 arylation of pyrroles been found to be tolerant to a very wide variety of
À
via a C H bond activation is reported. Only 0.5–0.01 functional groups on the aryl bromides such as
mol% of commercially available and air-stable formyl, acetyl, propionyl, ester, nitrile, nitro, fluoro,
ligand-free palladium(II) acetate [Pd
ACHTUNGRTENUN(NG OAc)2] was methoxy, amino or trifluoromethyl.
employed as the catalyst. The presence of electron-
withdrawing substituents such as formyl, acetyl or Keywords: aryl bromides; atom-economy; C H
ester at the C-2 position of the pyrrole is tolerated. bond activation; palladium; pyrroles
À
Introduction
phenes, thiazoles, oxazoles or indoles via a palladium-
catalyzed C H bond activation has been largely de-
À
Arylpyrrole derivatives continue to attract the atten- scribed in recent years.[6–11] On the other hand, the re-
tion of synthetic organic chemists, due to their inher- gioselective direct 2- or 5-arylation of pyrroles has at-
ent biological activity. Conventional methods for the tracted less attention. Some examples of regioselec-
synthesis of 2- or 5-arylpyrroles include metal-cata- tive intramolecular cyclization of pyrrole derivatives
lyzed cross-coupling reactions[1] such as Suzuki,[2] have been reported.[12] A few selective intermolecular
Stille,[3] Negishi[4] or Kumada[5] type reactions. They C-2 or C-5 arylation of pyrroles via palladium-cata-
À
make possible either the coupling of aryl halides with lyzed C H bond activation have also been de-
organometallic derivatives of pyrroles or the coupling scribed.[13,14] Some of these couplings employed metal
of
halopyrroles
with
aryl-metal
derivatives pyrrolyl salts as reactants.[13] The use of such salts
(Scheme 1). Nevertheless, these procedures require allows a high regiocontrol of the arylation, but produ-
the preliminary preparation of an organometallic de- ces a metallic salt as waste. Only a few results using
rivative, and produce stoichiometric amounts of met- pyrroles have been reported so far.[14] In 1992 Ohta
allic salts as by-products.
and co-workers described the direct arylation of N-
The direct regioselective couplings of pyrroles with phenylsulfonylpyrrole using 3,6-dialkyl-2-chloropyra-
aryl halides via C H bond activation/functionalization zines as coupling partners.[14a] In the course of these
À
would provide cost-effective and environmentally at- reactions, mixtures of 2- and 3-arylated pyrroles (C-
tractive accesses to arylpyrroles. The selective C-2 or 2:C-3 arylation, ratios from 1:1 to 2:5) were obtained.
C-5 arylation of heteroaromatics such as furans, thio- The coupling reaction of 3-bromopyridine with pyr-
Scheme 1.
Adv. Synth. Catal. 2009, 351, 1977 – 1990
ꢁ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1977

Julien Roger and Henri Doucet
FULL PAPERS
roles, using PdCl
G
First, we studied the coupling of 1-methyl-2-formyl-
gave a mixture of 2-pyridylpyrrole and N-pyridylpyr- pyrrole with 4-bromoacetophenone using 0.01 mol%
role in 46% and 21% yields, respectively.[14b] In 2006, of Pd
AHCTUNGTRENNUNG
Sames and co-workers have reported the direct aryla- 1508C for 17 h. We obtained 1 in only 27% yield
tion of a 3-acetylpyrrole using iodobenzene as cou- (Scheme 2, Table 1, entry 1). The use of other solvents
pling partner. 5 mol% of palladium associated to a
carbene ligand were used as catalyst.[14c] However,
again, a mixture of regioisomers was formed. 5-
Phenyl-3-acetylpyrrole was obtained in 29% yield;
whereas, 2-phenyl-3-acetylpyrrole and 2,5-diphenyl-3-
acetylpyrrole were produced in 7% and 14% yields,
respectively. This group also reported the direct 5-ary-
lation of methyl pyrrole-2-carboxylate with iodoben-
zene using 5 mol% of PdACTHNUTRGNEUNG
(OAc)2 as catalyst.[14d] Again,
the target product was obtained in a low yield of
30%. Very recently, Fagnou and co-workers have re-
ported three examples of 5-arylation of 2-substituted
Scheme 2.
pyrroles. They employed 2 mol% of PdACTHNUTRGNE(NUG OAc)2, such as DMF, NMP or dioxane did not allow us to im-
4 mol% of air-sensitive PCy3 and 30 mol% of pivalic prove the yield (Table 1, entries 2–4). A similar yield
acid as catalytic system.[14e] Using this procedure, the of 26% was obtained using toluene (Table 1, entry 5).
expected products were obtained in 52–69% yields. Then, we increased the catalyst loading to 0.05 mol%
Recently, a palladium ligand-free procedure for the 2- using DMAc or toluene as the solvent. A high yield
arylation of caffeine has also been described.[15] In of 76% of 1 was obtained using DMAc; whereas, tol-
summary, the yields, substrate scope of both coupling uene gave a very low yield of 6% (Table 1, entries 6
partners, regioselectivities and substrate/catalyst and 7). Toluene is apparently not a sufficiently polar
ratios for the direct arylation of pyrroles need to be solvent to stabilize relatively high concentrations of
largely improved in order to provide an environmen- ligand-less palladium species. As expected, lower re-
tally attractive and industrially viable procedure. action temperatures of 130 or 1008C led to lower
Here, we wish to report on the regioselective 2- or 5- yields (Table 1, entries 8 and 9). Then, the influence
arylation of pyrrole derivatives in the presence of low of several bases was investigated using 0.05 mol% of
loadings of a ligand-less palladium catalyst using a Pd
wide variety of aryl bromides.
ACHTUNGRTENUN(NG OAc)2, DMAc, 1508C as reaction conditions. The
reactions performed with Na2CO3, K2CO3 or Cs2CO3
as the base gave 1 in 63–84% yields (Table 1, en-
tries 11–13). KF was found to be an ineffective base
(Table 1, entry 10). The use of NaOAc as the base led
to a lower yield than KOAc: 35% yield instead of
Results and Discussion
We initially directed our efforts towards the palladi- 76% yield (Table 1, entries 6 and 14). In the presence
um-catalyzed direct 5-arylation of 1-methyl-2-formyl- of [PdCl(C3H5)]2 as palladium source, a lower yield of
AHCTUNGTRENNUNG
pyrrole with 4-bromoacetophenone, using the recently 1 was also obtained (Table 1, entry 20). For this reac-
reported ligand-free palladium reaction conditions tion, the presence of ligands such as PPh3 or bidentate
employed for the direct arylation of furans, thio- phosphines did not enable us to increase the yields
phenes or thiazoles.[7e,8g,9e] At elevated temperature, (Table 1, entries 16–19 and 21–23).
according to de Vries,[16] when ligand-free Pd
G
Then, we examined the scope and limitations of
is employed as catalyst precursor, soluble palladi- this ligand-less palladium procedure using a wide vari-
um(0) colloids or nanoparticles are formed. These ety of aryl bromides (Scheme 3, Table 2 and Table 3).
nanoparticles seem to produce monomeric or dimeric In the presence of para-substituted electron-deficient
anionic palladium complexes that are very active cata- aryl bromides such as 4-bromobenzaldehyde, 4-bro-
lysts. For this ligand-free procedure, low catalyst load- mopropiophenone,
4-bromobenzonitrile
or
4-
ings have to be employed (less than 0.5 mol%). In the trifluoromethylbromobenzene, the expected com-
AHCTUNGTRENNUNG
presence of higher palladium loadings (>1 mol%), pounds 2, 3, 5 and 7 were obtained in good yields
so-called “palladium black”, which is generally inac- using only 0.1 mol% catalyst. Even poorly activated
tive for such catalyzed reactions, is produced more 4-fluorobromobenzene gave a good yield of 8 using
rapidly. Consequently, in the absence of stabilizing 0.1 mol% catalyst (Table 2, entry 12). For these reac-
agent, the conversions of the aryl halides and the tions KOAc was employed as the base. It should be
yields of coupling products are generally not in- noted that in the presence of 4-bromopropiophenone,
creased by using a high catalyst loading (5–10 mol%). 4-trifluoromethylbromobenzene or 4-fluorobromo-
benzene, the use of K2CO3 as the base gave low con-
1978
asc.wiley-vch.de
ꢁ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2009, 351, 1977 – 1990

Regioselective C-2 or C-5 Direct Arylation of Pyrroles with Aryl Bromides
FULL PAPERS
Table 1. Pd-catalyzed direct arylation of 1-methyl-2-formylpyrrole (Scheme 2).[a]
Entry
Catalyst
Ratio Substrate/Catalyst
Base
Solvent
Temp. [8C]
Yield. [%]
1
2
3
4
5
6
7
8
Pd
Pd
Pd
Pd
Pd
Pd
Pd
Pd
Pd
Pd
Pd
Pd
Pd
Pd
Pd
Pd
Pd
Pd
Pd
N
10,000
10,000
10,000
10,000
10,000
2000
KOAc
KOAc
KOAc
KOAc
KOAc
KOAc
KOAc
KOAc
KOAc
KF
Cs2CO3
Na2CO3
K2CO3
NaOAc
KOAc
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
DMAc
DMF
NMP
150
150
150
150
150
150
150
130
100
150
150
150
150
150
150
150
150
150
150
150
150
150
150
27
0
2
dioxane
toluene
DMAc
toluene
DMAc
DMAc
DMAc
DMAc
DMAc
DMAc
DMAc
DMAc
DMAc
DMAc
DMAc
DMAc
DMAc
DMAc
DMAc
DMAc
0
26
76
6
8
3
2000
10,000
10,000
2000
2000
2000
2000
2000
1000
2000
2000
2000
2000
2000
2000
2000
2000
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
0
83
63
84
35
100 (90)
36
61
64
67
61
16
3
[Pd
[Pd
[Pd
[Pd
G
E
N
G
38
[a]
Conditions: 4-bromoacetophenone (1 mmol), 1-methyl-2-formylpyrrole (2 mmol), base (2 mmol), solvent (3 mL), 17 h,
GC and NMR yields, yield in parenthesis is isolated.
Scheme 3.
versions of these aryl bromides (Table 2, entries 4, 11 hand, when 0.5 mol% of catalyst was employed, the
and 13). With deactivated aryl bromides, the oxidative use of K2CO3 generally led to similar or higher yields
addition to palladium is generally slower. We ob- than KOAc, especially for the reactions performed
tained satisfactory results using 4-bromotoluene or 4- with deactivated aryl bromides. We believe that
bromoanisole, but on the other hand, with 4-tert-bu- K2CO3 is a more suitable base for stabilizing ligand-
tylbromobenzene or 4-bromo-N,N-dimethylaniline, less palladium species; whereas, KOAc associated to
moderate yields of 10 and 12 were obtained using palladium gives less stable but more active palladium
KOAc as the base (Table 2, entries 14–25). Surprising- species.
ly, with these deactivated aryl bromides good yields
were generally obtained using K2CO3 as the base and substituted aryl bromides and also heteroaryl bro-
0.5 mol% catalyst (Table 2, entries 17 and 23). mides with 1-methyl-2-formylpyrrole (Table 3). The
Next, we studied the reactivity of meta- or ortho-
These results reveal that, as expected, the stability meta-substituted aryl bromides, 3-bromobenzalde-
of the palladium active species largely depends on the hyde, 3-bromobenzonitrile or 2-bromonaphthalene,
palladium concentration. However, it also depends on using KOAc as the base, gave satisfactory results
the nature of the base. In general, when 0.1 mol% using only 0.5–0.1 mol% of catalyst (Table 3, en-
catalyst was employed, the use of KOAc as the base tries 1–6). ortho-Substituents on the aryl bromides
gave higher conversions of the aryl bromides than generally have a more important effect on the reac-
with K2CO3. Under such low palladium concentra- tions rates and yields, for most palladium-catalyzed
tions, the aggregation of palladium into “palladium reactions, due to their steric and/or coordination
black” seems to be relatively slow. On the other properties. However, good yields of coupling products
Adv. Synth. Catal. 2009, 351, 1977 – 1990
ꢁ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
1979

Julien Roger and Henri Doucet
Table 2. Pd-catalyzed direct arylation of 1-methyl-2-formylpyrrole using para-substituted aryl bromides (Scheme 3).[a]
FULL PAPERS
Entry
Aryl Bromide
Major Product
Base
Ratio Substrate/Catalyst
Yield [%]
1
2
KOAc
KOAc
1000
10,000
88 (80)
30
2
3
4
5
6
7
8
9
3
4
KOAc
K2CO3
1000
200
91 (81)
30
5
6
KOAc
KOAc
200
1000
77 (70)
42
7
8
KOAc
KOAc
1000
10,000
90 (81)
14
9
KOAc
1000
68 (61)
10
11
KOAc
K2CO3
1000
1000
93 (84)
31
12
13
KOAc
K2CO3
1000
1000
92 (84)
19
14
15
KOAc
K2CO3
1000
1000
88 (81)
80
16
17
18
19
KOAc
K2CO3
KOAc
K2CO3
200
200
1000
1000
10
81 (73)
50
10
11
12
43
20
21
KOAc
K2CO3
200
200
66
83 (74)
22
23
24
25
KOAc
K2CO3
KOAc
K2CO3
200
200
1000
1000
33
79 (71)
15
43
[a]
Conditions: PdACHTUNGTRENNUNG(OAc)2, aryl bromide (1 mmol), 1-methyl-2-formylpyrrole (2 mmol), K2CO3 or KOAc (2 mmol), DMAc
(3 mL), 1508C, 17 h, GC and NMR yields, yields in parenthesis are isolated.
16, 17 or 20 were obtained in the presence of 2-bro- dines or quinolines are p-electron deficient heterocy-
mobenzonitrile, 2-bromobenzaldehyde or 1-bromo- cles. Therefore, their reactivity is quite similar to that
naphthalene (Table 3, entries 7, 8 and 13). These reac- of the electron-deficient aryl bromides. As expected,
tions were performed using only 0.1 mol% of catalyst. using 3- or 4-bromopyridines, or 3-bromoquinoline,
2-Fluorobromobenzene or 2,4-difluorobromobenzene the coupling products 21–23 were obtained in high
were found to be slightly less reactive substrates. With yields using only 0.5–0.1 mol% of catalyst and KOAc
these reactants, 0.5 mol% of catalyst had to be em- as the base (Table 3, entries 14–19).
ployed. Under this palladium concentration, K2CO3
used as the base gave higher yields than KOAc active coupling partner. Using the PdAHCNUTGTRENNUNG
1-Methyl-2-acetylpyrrole was also found to be a re-
(OAc)2 ligand-
(Table 3, entries 9–12). Then, we examined the reac- less procedure, this pyrrole gave the 5-arylation prod-
tivity of a few heteroaryl bromides. Palladium chemis- ucts in high regioselectivities and yields (Scheme 4,
try involving heterocycles has its unique characteris- table 4). Again, the electron-deficient aryl bromides
tics stemming from the heterocycleꢂs inherently differ- such as 4-trifluoromethylbromobenzene, 4-bromoben-
ent structural and electronic properties in comparison zonitrile or 4-fluorobromobenzene gave satisfactory
to the corresponding carbocyclic aryl compound. Pyri- results using 0.5–0.1 mol% of catalyst and KOAc as
1980
asc.wiley-vch.de
ꢁ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2009, 351, 1977 – 1990

Regioselective C-2 or C-5 Direct Arylation of Pyrroles with Aryl Bromides
FULL PAPERS
Table 3. Pd-catalyzed direct arylation of 1-methyl-2-formylpyrrole using meta-, or ortho-substituted aryl bromides and
hetero
ACHTUNGTRENNUNG
Entry
Major Product
Base
Substrate/Catalyst Ratio
Yield [%]
1
2
KOAc
K2CO3
200
200
67 (60)
66
13
3
4
KOAc
KOAc
200
1000
90 (82)
77
14
15
5
6
KOAc
KOAc
1000
10,000
91 (82)
46
7
8
16
17
18
19
KOAc
KOAc
1000
1000
85 (79)
78 (69)
9
10
KOAc
K2CO3
200
200
52
63 (54)
11
12
KOAc
K2CO3
200
200
63
75 (69)
13
20
KOAc
1000
84 (77)
14
15
KOAc
KOAc
1000
10,000
88 (80)
25
21
22
23
16
17
KOAc
KOAc
200
1000
79 (70)[b]
40[b]
18
19
KOAc
KOAc
1000
10,000
86 (78)
40
[a]
Conditions: PdACHTUNGTRENNUNG(OAc)2, aryl bromide (1 mmol), 1-methyl-2-formylpyrrole (2 mmol), K2CO3 or KOAc (2 mmol), DMAc
(3 mL), 1508C, 17 h, GC and NMR yields, yields in parenthesis are isolated.
KOAc: 3 mmol.
[b]
the base (Table 4, entries 1–8). As expected, in the bromotoluene was found to be less reactive. The best
presence of deactivated aryl bromides, using KOAc as yield was obtained using 0.5 mol% of catalyst and
the base and 0.5 mol% catalyst, quite low conversions KOAc as the base (Table 4, entries 22 and 23). With
were generally obtained (Table 4, entries 9, 11, 13 and this challenging substrate, the use of palladium associ-
17). On the other hand, in the presence of K2CO3 as ated to phosphine ligands would certainly give higher
the base, 4-bromotoluene, 4-tert-butylbromobenzene, yields.[14e] 1-Bromonaphthalene or 3-bromopyridine
4-bromoanisole or 4-N,N-dimethylaminobromoben- have also been reacted with 1-methyl-2-acetylpyrrole.
zene gave the desired coupling products 27–30 in 73– These substrates, in the presence of KOAc as the
82% yields (Table 4, entries 10, 12, 15 and 18). The base, gave 34 and 35 in high yields and high TONs
sterically congested and deactivated aryl bromide, 2- (Table 4, entries 24–31).
Adv. Synth. Catal. 2009, 351, 1977 – 1990
ꢁ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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1981

Julien Roger and Henri Doucet
FULL PAPERS
Scheme 4.
Table 4. Pd-catalyzed direct 5-arylation of 1-methyl-2-acetylpyrrole (Scheme 4).[a]
Entry
Aryl Bromide
Major Product
Base
Substrate/Catalyst Ratio
Yield [%]
1
2
3
4
KOAc
KOAc
K2CO3
K2CO3
200
1000
200
74 (66)
53
74
24
1000
20
5
6
KOAc
KOAc
200
1000
92 (81)
77
25
26
27
28
7
8
KOAc
K2CO3
1000
1000
93 (80)
20
9
10
KOAc
K2CO3
200
200
12
82 (73)
11
12
KOAc
K2CO3
200
200
21
94 (82)
13
14
15
16
KOAc
KOAc
K2CO3
K2CO3
200
1000
200
56
53
88 (80)
23
29
1000
17
18
KOAc
K2CO3
200
200
12
82 (74)
30
31
19
20
KOAc
KOAc
1000
10,000
92 (83)
11
21
32
33
KOAc
1000
77 (70)
22
23
KOAc
K2CO3
200
200
42 (37)
26
24
25
26
27
KOAc
KOAc
KOAc
K2CO3
200
89 (80)
85
71
1000
10,000
200
34
35
85
28
29
30
31
KOAc
KOAc
K2CO3
K2CO3
200
1000
200
92 (84)
74
89
1000
49
[a]
Conditions: Pd
ACHTUNGTRENNUNG(OAc)2, aryl bromide (1 mmol), 1-methyl-2-acetylpyrrole (2 mmol), K2CO3 or KOAc (2 mmol), DMAc
(3 mL), 1508C, 17 h, GC and NMR yields, yields in parenthesis are isolated.
1982
asc.wiley-vch.de
ꢁ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2009, 351, 1977 – 1990

Regioselective C-2 or C-5 Direct Arylation of Pyrroles with Aryl Bromides
FULL PAPERS
Scheme 5.
Table 5. Pd-catalyzed direct 5-arylation of methyl 1-methyl-2-pyrrolecarboxylate (Scheme 5).[a]
Entry
Aryl Bromide
Major Product
Yield [%]
1
36
37
38
92 (83)
2
87 (80)[b]
60 (52)[b]
3
[a]
Conditions: PdACHTUNGTRENNUNG(OAc)2 (0.001 mmol), aryl bromide (1 mmol), methyl 1-methyl-2-pyrrolecarboxylate (2 mmol), KOAc
(2 mmol), DMAc (3 mL), 1508C, 5 h, GC and NMR yields, yields in parenthesis are isolated.
Reaction time 2 h.
[b]
We initially obtained quite disappointing results products 36–38 were obtained in moderate to high
using methyl 1-methyl-2-pyrrolecarboxylate as reac- yields, and only a minor amount of 1-methyl-2-aryl-
tant (Scheme 5, Table 5). With this substrate, when pyrroles was detected. It should be noted that all
the reactions were stopped after 17 h, mixtures of the these reactions were performed using only 0.1 mol%
expected 5-arylated pyrroles 36–38 and 2-arylpyrroles of catalyst.
arising from decarboxylation were obtained. Up to
This procedure is not limited to the use of 2-substi-
50% of these decarboxylated pyrroles could be tuted pyrroles. We observed that the selective 2-aryla-
formed. However, the GC analysis of the reactions tion of 1-methylpyrrole also proceeded nicely
mixtures at 1 h, 2 h and 5 h revealed that this decar- (Scheme 6, Table 6). However, in the course of this
boxylation process was relatively slow, as compared reaction, the formation of 2,5-diarylpyrroles was pos-
to the palladium-catalyzed 5-arylation rate. When the sible. In order to reduce the amount of these 2,5-di-
reactions were stopped after 2 h or 5 h, the target
ACHTUNGTRENaNGNU rylpyrroles, we employed four equivalents of this
coupling partner. Using these reaction conditions, we
observed that the 2-arylation of 1-methylpyrrole with
4-bromobenzonitrile was very fast. This reaction pro-
ceeds nicely to give 39 in 80% yield using only
0.01 mol% of catalyst (Table 6, entry 1). Moreover,
only trace amounts of the diarylated pyrrole side-
product were detected by GC and GC/MS analysis.
As expected, with the more challenging 4-bromoani-
Scheme 6.
Table 6. Pd-catalyzed direct 2-arylation of 1-methylpyrrole (Scheme 6).[a]
Entry
Aryl Bromide
Major Product
Substrate/Catalyst Ratio
10000
Yield [%]
91 (80)
1
39
40
2
1000
78 (70)
[a]
Conditions: Pd
ACHTUNGTRENNUNG(OAc)2, aryl bromide (1 mmol), 1-methylpyrrole (4 mmol), KOAc (2 mmol), DMAc (3 mL), 1508C, 17 h, GC
and NMR yields, yields in parenthesis are isolated.
Adv. Synth. Catal. 2009, 351, 1977 – 1990
ꢁ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
1983

Julien Roger and Henri Doucet
FULL PAPERS
sole, the reaction was slower. In order to obtain a tuted 2,5-diarylpyrroles. As expected, using 39 and 3-
good conversion of this aryl bromide, we had to bromopyridine as coupling partners, 45 was obtained
employ 0.1 mol% of catalyst (Table 6, entry 2). With in 72% yield (Scheme 8). This successive arylation
this substrate, approximately 18% of the diarylated method should allow the synthesis of a very wide vari-
pyrrole was also produced.
ety of 2,5-diarylpyrroles in only two steps.
Quite similar results were obtained using 1-phenyl-
Finally, we studied the regioselectivity of the direct
pyrrole (Scheme 7, Table 7). Electron-deficient aryl arylation of 1-methylindole with 4-bromoacetophe-
bromides were reacted using only 0.01 mol% of cata- none using our ligand-less palladium procedure.
lyst, whereas electron-excessive ones required Sames and co-worker had observed that for the reac-
0.1 mol% of Pd
ACHTUNGTRENNUNG
aryl-1-phenylpyrroles 41–44 were obtained, and only using 0.5 mol% of PdAHCTNUGTRENNNUG
small amounts of diarylpyrroles were formed.
As position C-5 of compounds 39–44 is very reac- obtained in 52% yield.[11a] Using our reaction condi-
tive towards palladium-catalyzed direct arylation, it tions, 4-bromoacetophenone, which is less expensive
should allow the synthesis of unsymmetrically substi- than 4-iodoacetophenone, regioselectively led to the
2-arylated indole 46 in 78% yield (Scheme 9). This re-
action was performed using only 0.1 mol% of Pd-
AHCTUNGRTEG(NNUN OAc)2 as catalyst.
Conclusions
In summary, we report here an atom-economical
method for the direct regioselective C-2 or C-5 aryla-
tion of pyrroles. This procedure employs a low cata-
lyst loading of a commercially available, ligand-less
Scheme 7.
Table 7. Pd-catalyzed direct 2-arylation of 1-phenylpyrrole (Scheme 7).[a]
Entry
Aryl Bromide
Major Product
Substrate/Catalyst Ratio
10,000
Yield [%]
92 (78)
1
41
42
43
44
2
3
10,000
1000
94 (80)
87 (70)
92 (73)
4
1000
[a]
Conditions: Pd
ACHTUNGTRENNUNG(OAc)2, aryl bromide (1 mmol), 1-phenylpyrrole (4 mmol), KOAc (2 mmol), DMAc (3 mL), 1508C, 17 h,
GC and NMR yields, yields in parenthesis are isolated.
Scheme 8.
1984
asc.wiley-vch.de
ꢁ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2009, 351, 1977 – 1990

Regioselective C-2 or C-5 Direct Arylation of Pyrroles with Aryl Bromides
FULL PAPERS
Scheme 9.
bromide. The solvent was removed by heating the reaction
vessel under vacuum and the residue was charged directly
onto a silica gel column. The products were eluted, using an
appropriate ratio of diethyl ether and pentane.
5-(4-Acetylphenyl)-1-methyl-2-formylpyrrole (1): The re-
action of 4-bromoacetophenone (0.200 g, 1 mmol), 1-methyl-
2-formylpyrrole (0.219 g, 2 mmol) and KOAc (0.196 g,
and air-stable palladium source. Therefore, there is no
need to eliminate phosphine derivatives at the end of
the reaction. Under such low catalyst concentrations,
palladium stabilizing agents such as ammonium salts
are useless, thus reducing the amount of wastes.
Moreover, both electron-excessive and electron-defi-
cient aryl bromides can be employed. In the presence
of electron-deficient aryl bromides, K2CO3 should be
employed as the base in some cases; whereas, with
electron-poor aryl bromides, KOAc should be pre-
ferred. This catalytic system has proven to be tolerant
to a variety of functional groups such as ester, formyl,
acetyl, nitrile, nitro, fluoro, methoxy, amino, or tri-
fluoromethyl on the aryl bromide. This reaction can
be performed using as little as 0.1–0.01 mol% of cata-
lyst with several substrates. Finally, this procedure is
environmentally attractive as the major by-products
are AcOK or K2CO3 associated to HBr instead of
metallic salts using more classical coupling proce-
dures.
2 mmol) with PdACTHNUTRGNEUNG(OAc)2 (0.22 mg, 0.001 mmol) affords the
corresponding product 1; isolated yield: 0.205 g (90%).
1H NMR (200 MHz, CDCl3): d=9.60 (s, 1H), 8.05 (d, J=
8.2 Hz, 2H), 7.54 (d, J=8.2 Hz, 2H), 7.00 (d, J=4.0 Hz,
1H), 6.38 (d, J=4.0 Hz, 1H), 3.95 (s, 3H), 2.65 (s, 3H);
13C NMR (50 MHz, CDCl3): d=196.4, 178.8, 141.7, 135.6,
134.5, 132.6, 128.2, 127.6, 123.4, 110.4, 33.5, 25.7; anal. calcd.
for C14H13NO2: C 73.99, H 5.77; found: C 73.87, H 5.71.
5-(4-Formylphenyl)-1-methyl-2-formylpyrrole (2): The re-
action of 4-bromobenzaldehyde (0.187 g, 1 mmol), 1-methyl-
2-formylpyrrole (0.219 g, 2 mmol) and KOAc (0.196 g,
2 mmol) with PdACTHNUTRGNEUNG(OAc)2 (0.22 mg, 0.001 mmol) affords the
corresponding product 2; isolated yield: 0.171 g (80%).
1H NMR (200 MHz, CDCl3): d=10.07 (s, 1H), 9.63 (s, 1H),
7.97 (d, J=8.0 Hz, 2H), 7.61 (d, J=8.0 Hz, 2H), 7.00 (d, J=
4.1 Hz, 1H), 6.40 (d, J=4.1 Hz, 1H), 3.97 (s, 3H); 13C NMR
(50 MHz, CDCl3): d=191.4, 179.9, 142.4, 136.9, 135.9, 133.8,
129.9, 129.6, 124.3, 111.6, 34.6; anal. calcd. for C13H11NO2: C
73.22, H 5.20; found: C 73.30, H 5.41.
5-(4-Propionylphenyl)-1-methyl-2-formylpyrrole (3): The
reaction of 4-bromopropiophenone (0.214 g, 1 mmol), 1-
methyl-2-formylpyrrole (0.219 g, 2 mmol) and KOAc
Experimental Section
General Remarks
All chemical reactants and palladium complexes were ob-
tained from commercial sources and used with out further
purification. DMAc analytical grade (99%) was not distilled
before use. K2CO3 or KOAc (99+%) were employed. All
reactions were run under argon using vacuum lines in
Schlenk tubes in oven-dried glassware. 1H (200 MHz) and
13C NMR (50 MHz) spectra were recorded in CDCl3 solu-
tions. Chemical shifts (d) are reported in ppm relative to
CDCl3. Flash chromatographies were performed on silica
gel (230–400 mesh).
(0.196 g, 2 mmol) with PdACTHNUTRGNE(NUG OAc)2 (0.22 mg, 0.001 mmol) af-
fords the corresponding product 3; isolated yield: 0.195 g
1
(81%). H NMR (200 MHz, CDCl3): d=9.60 (s, 1H), 8.05
(d, J=8.2 Hz, 2H), 7.52 (d, J=8.2 Hz, 2H), 7.00 (d, J=
4.0 Hz, 1H), 6.37 (d, J=4.0 Hz, 1H), 3.95 (s, 3H), 3.03 (q,
J=7.6 Hz, 2H), 1.25 (t, J=7.6 Hz, 3H); 13C NMR (50 MHz,
CDCl3): d=196.4, 179.7, 136.4, 135.2, 133.4, 129.1, 128.1,
124.2, 121.9, 111.2, 34.4, 31.7, 8.1; anal. calcd. for
C15H15NO2: C 74.67, H 6.27; found: C 74.80, H 6.47.
Methyl 4-(5-formyl-1-methylpyrrol-2-yl)-benzoate (4):
The reaction of methyl 4-bromobenzoate (0.216 g, 1 mmol),
1-methyl-2-formylpyrrole (0.219 g, 2 mmol) and KOAc
General Procedure
In a typical experiment, the aryl bromide (1 mmol), pyrrole
derivative (2 mmol) and KOAc or K2CO3 (2 mmol, see
Tables) were introduced in a Schlenk tube, equipped with a
(0.196 g, 2 mmol) with PdACTHNUTRGNE(UNG OAc)2 (1.1 mg, 0.005 mmol) af-
fords the corresponding product 4; isolated yield: 0.170 g
1
(70%). H NMR (200 MHz, CDCl3): d=9.61 (s, 1H), 8.13
magnetic stirring bar. The PdACHTUNRGTNEUNG(OAc)2 (see Tables) and
(d, J=8.2 Hz, 2H), 7.51 (d, J=8.2 Hz, 2H), 7.00 (d, J=
4.0 Hz, 1H), 6.38 (d, J=4.0 Hz, 1H), 3.96 (s, 6H); 13C NMR
(50 MHz, CDCl3): d=179.8, 166.5, 142.8, 135.5, 133.6, 130.0,
129.9, 129.0, 124.4, 111.3, 52.3, 34.5; anal. calcd. for
C14H13NO3: C 69.12, H 5.39; found: C 69.21, H 5.27.
DMAc (3 mL) were added, and the Schlenk tube purged
several times with argon. The Schlenk tube was placed in a
pre-heated oil bath at 1508C and reactants were allowed to
stir for 17 h. Then, the reaction mixture was analyzed by gas
chromatography to determine the conversion of the aryl
Adv. Synth. Catal. 2009, 351, 1977 – 1990
ꢁ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
1985

Julien Roger and Henri Doucet
FULL PAPERS
1
4-(5-Formyl-1-methylpyrrol-2-yl)-benzonitrile (5): The re-
action of 4-bromobenzonitrile (0.182 g, 1 mmol), 1-methyl-2-
formylpyrrole (0.219 g, 2 mmol) and KOAc (0.196 g,
(73%). H NMR (200 MHz, CDCl3): d=9.59 (s, 1H), 7.51
(d, J=8.3 Hz, 2H), 7.38 (d, J=8.3 Hz, 2H), 7.00 (d, J=
4.1 Hz, 1H), 6.32 (d, J=4.1 Hz, 1H), 3.97 (s, 3H), 1.30 (s,
9H); 13C NMR (50 MHz, CDCl3): d=179.4, 151.7, 144.4,
132.8, 128.8, 126.0, 125.5, 124.5, 110.6, 34.7, 34.4, 31.2; anal.
calcd. for C16H19NO: C 79.63, H 7.94; found: C 79.47, H
7.88.
2 mmol) with PdACHTUNGTRENNUNG(OAc)2 (0.22 mg, 0.001 mmol) affords the
corresponding product 5; isolated yield: 0.171 g (81%).
1H NMR (200 MHz, CDCl3): d=9.61 (s, 1H), 7.75 (d, J=
8.2 Hz, 2H), 7.54 (d, J=8.2 Hz, 2H), 7.00 (d, J=4.1 Hz,
1H), 6.37 (d, J=4.1 Hz, 1H), 3.94 (s, 3H); 13C NMR
(50 MHz, CDCl3): d=179.9, 141.6, 135.5, 133.8, 132.4, 129.6,
124.2, 118.3, 112.1, 111.6, 34.5; anal. calcd. for C13H10N2O: C
74.27, H 4.79; found: C 73.98, H 4.61.
5-(4-Methoxylphenyl)-1-methyl-2-formylpyrrole (11): The
reaction of 4-bromoanisole (0.187 g, 1 mmol), 1-methyl-2-
formylpyrrole (0.219 g, 2 mmol) and K2CO3 (0.278 g,
2 mmol) with PdACTHNUTRGNEUNG(OAc)2 (1.1 mg, 0.005 mmol) affords the
5-(4-Nitrophenyl)-1-methyl-2-formylpyrrole (6): The reac-
tion of 4-bromonitrobenzene (0.202 g, 1 mmol), 1-methyl-2-
formylpyrrole (0.219 g, 2 mmol) and KOAc (0.196 g,
corresponding product 11; isolated yield: 0.159 g (74%).
1H NMR (200 MHz, CDCl3): d=9.56 (s, 1H), 7.36 (d, J=
8.3 Hz, 2H), 7.01 (d, J=8.3 Hz, 2H), 6.99 (d, J=4.1 Hz,
1H), 6.27 (d, J=4.1 Hz, 1H), 3.93 (s, 3H), 3.87 (s, 3H);
13C NMR (50 MHz, CDCl3): d=179.2, 159.7, 144.1, 132.6,
130.3, 124.4, 123.2, 113.2, 110.2, 55.2, 34.1; anal. calcd. for
C13H13NO2: C 72.54, H 6.09; found: C 72.37, H 6.01.
5-(4-Dimethylaminophenyl)-1-methyl-2-formylpyrrole
(12):[17] The reaction of 4-bromo-N,N-dimethylaniline
(0.200 g, 1 mmol), 1-methyl-2-formylpyrrole (0.219 g,
2 mmol) with PdACHTUNGTRENNUNG(OAc)2 (0.22 mg, 0.001 mmol) affords the
corresponding product 6; isolated yield: 0.140 g (61%).
1H NMR (200 MHz, CDCl3): d=9.62 (s, 1H), 8.32 (d, J=
8.2 Hz, 2H), 7.60 (d, J=8.2 Hz, 2H), 7.01 (d, J=4.1 Hz,
1H), 6.41 (d, J=4.1 Hz, 1H), 3.96 (s, 3H); 13C NMR
(50 MHz, CDCl3): d=179.6, 147.4, 141.2, 137.4, 134.0, 129.2,
123.8, 123.4, 111.4, 34.1; anal. calcd. for C12H10N2O3: C
62.60, H 4.38; found: C 62.47, H 4.45.
5-(4-Trifluoromethylphenyl)-1-methyl-2-formylpyrrole (7):
The reaction of 4-trifluoromethylbromobenzene (0.225 g,
1 mmol), 1-methyl-2-formylpyrrole (0.219 g, 2 mmol) and
2 mmol) and K2CO3 (0.278 g, 2 mmol) with PdACHTUNGTRENNUNG(OAc)2
(1.1 mg, 0.005 mmol) affords the corresponding product 12;
1
isolated yield: 0.162 g (71%). H NMR (200 MHz, CDCl3):
d=9.54 (s, 1H), 7.32 (d, J=8.3 Hz, 2H), 6.97 (d, J=4.1 Hz,
1H), 6.79 (d, J=8.3 Hz, 2H), 6.26 (d, J=4.1 Hz, 1H), 3.96
(s, 3H), 3.04 (s, 6H).
5-(3-Formylphenyl)-1-methyl-2-formylpyrrole (13): The
reaction of 3-bromobenzaldehyde (0.187 g, 1 mmol), 1-
methyl-2-formylpyrrole (0.219 g, 2 mmol) and KOAc
KOAc (0.196 g, 2 mmol) with PdACTHNUTRGNEUNG(OAc)2 (0.22 mg,
0.001 mmol) affords the corresponding product 7; isolated
1
yield: 0.213 g (84%). H NMR (200 MHz, CDCl3): d=9.64
(s, 1H), 7.75 (d, J=8.2 Hz, 2H), 7.57 (d, J=8.2 Hz, 2H),
7.02 (d, J=4.1 Hz, 1H), 6.38 (d, J=4.1 Hz, 1H), 3.96 (s,
3H); 13C NMR (50 MHz, CDCl3): d=179.8, 134.7, 133.5,
131.1, 129.5, 129.3 (q, J=32.5 Hz), 125.6 (m), 125.5 (q, J=
272.5 Hz), 124.3, 111.3, 34.4; anal. calcd. for C13H10F3NO: C
61.66, H 3.98; found: C 61.90, H 4.14.
5-(4-Fluorophenyl)-1-methyl-2-formylpyrrole (8): The re-
action of 4-bromofluorobenzene (0.175 g, 1 mmol), 1-
methyl-2-formylpyrrole (0.219 g, 2 mmol) and KOAc
(0.196 g, 2 mmol) with PdACTHNUTRGNE(UNG OAc)2 (1.1 mg, 0.005 mmol) af-
fords the corresponding product 13; isolated yield: 0.128 g
1
(60%). H NMR (200 MHz, CDCl3): d=10.07 (s, 1H), 9.61
(s, 1H), 7.98–7.90 (m, 3H), 7.70–7.60 (m, 1H), 7.00 (d, J=
4.1 Hz, 1H), 6.36 (d, J=4.1 Hz, 1H), 3.94 (s, 3H); 13C NMR
(50 MHz, CDCl3): d=191.4, 179.9, 142.4, 136.7, 134.8, 133.4,
132.2, 130.1, 129.8, 129.5, 124.4, 111.2, 34.4; anal. calcd. for
C13H11NO2: C 73.22, H 5.20; found: C 73.41, H 5.37.
3-(5-Formyl-1-methylpyrrol-2-yl)-benzonitrile (14): The
reaction of 3-bromobenzonitrile (0.182 g, 1 mmol), 1-methyl-
2-formylpyrrole (0.219 g, 2 mmol) and KOAc (0.196 g,
(0.196 g, 2 mmol) with PdACTHNUTRGNE(NUG OAc)2 (0.22 mg, 0.001 mmol) af-
fords the corresponding product 8; isolated yield: 0.171 g
1
(84%). H NMR (200 MHz, CDCl3): d=9.59 (s, 1H), 7.42
(dd, J=8.5 and 5.9 Hz, 2H), 7.17 (t, J=8.5 Hz, 2H), 7.00 (d,
J=3.8 Hz, 1H), 6.29 (d, J=3.8 Hz, 1H), 3.92 (s, 3H);
13C NMR (50 MHz, CDCl3): d=179.5, 162.8 (d, J=
249.1 Hz), 143.0, 132.9, 131.0 (d, J=8.2 Hz), 127.1 (m),
124.3, 115.8 (d, J=21.8 Hz), 110.0, 34.1; anal. calcd. for
C12H10FNO: C 70.93, H 4.96; found: C 70.89, H 4.78.
5-(4-Methylphenyl)-1-methyl-2-formylpyrrole (9): The re-
action of 4-bromotoluene (0.171 g, 1 mmol), 1-methyl-2-for-
mylpyrrole (0.219 g, 2 mmol) and KOAc (0.196 g, 2 mmol)
2 mmol) with PdACTHNUTRGNEUNG(OAc)2 (1.1 mg, 0.005 mmol) affords the
corresponding product 14; isolated yield: 0.172 g (82%).
1H NMR (200 MHz, CDCl3): d=9.61 (s, 1H), 7.80–7.60 (m,
4H), 6.99 (d, J=4.1 Hz, 1H), 6.33 (d, J=4.1 Hz, 1H), 3.92
(s, 3H); 13C NMR (50 MHz, CDCl3): d=180.0, 141.2, 133.5,
133.3, 132.5, 132.4, 131.9, 129.6, 124.2, 118.1, 113.2, 111.3,
34.4; anal. calcd. for C13H10N2O: C 74.27, H 4.79; found: C
74.44, H 4.62.
1-Methyl-5-naphthalen-2-ylpyrrole-2-carbaldehyde (15):
The reaction of 2-bromonaphthalene (0.207 g, 1 mmol), 1-
methyl-2-formylpyrrole (0.219 g, 2 mmol) and KOAc
with PdACHTUNGTRENNUNG(OAc)2 (0.22 mg, 0.001 mmol) affords the corre-
1
sponding product 9; isolated yield: 0.162 g (81%). H NMR
(200 MHz, CDCl3): d=9.59 (s, 1H), 7.34 (d, J=8.5 Hz, 2H),
7.28 (d, J=8.5 Hz, 2H), 7.00 (d, J=4.1 Hz, 1H), 6.30 (d, J=
4.1 Hz, 1H), 3.94 (s, 3H), 2.44 (s, 3H); 13C NMR (50 MHz,
CDCl3): d=179.3, 144.3, 138.5, 132.7, 129.2, 126.9, 128.0,
124.4, 110.4, 34.2, 21.2; anal. calcd. for C13H13NO: C 78.36,
H 6.58; found: C 78.39, H 6.68.
(0.196 g, 2 mmol) with PdACTHNUTRGNE(NUG OAc)2 (0.22 mg, 0.001 mmol) af-
fords the corresponding product 15; isolated yield: 0.193 g
1
(82%). H NMR (200 MHz, CDCl3): d=9.65 (s, 1H), 8.00–
7.90 (m, 4H), 7.62–7.40 (m, 3H), 7.05 (d, J=4.1 Hz, 1H),
6.44 (d, J=4.1 Hz, 1H), 4.02 (s, 3H); 13C NMR (50 MHz,
CDCl3): d=179.5, 144.1, 133.0, 132.9, 132.8, 128.5, 128.3,
128.2, 128.1, 127.7, 126.8, 126.7, 126.5, 124.5, 111.0, 34.4;
anal. calcd. for C16H13NO: C 81.68, H 5.57; found: C 81.77,
H 5.41.
5-(4-tert-Butylphenyl)-1-methyl-2-formylpyrrole (10): The
reaction of 4-tert-butylbromobenzene (0.213 g, 1 mmol), 1-
methyl-2-formylpyrrole (0.219 g, 2 mmol) and K2CO3
(0.278 g, 2 mmol) with Pd
ACHTUNGRTEN(NUNG OAc)2 (1.1 mg, 0.005 mmol) af-
fords the corresponding product 10; isolated yield: 0.176 g
1986
asc.wiley-vch.de
ꢁ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2009, 351, 1977 – 1990

Regioselective C-2 or C-5 Direct Arylation of Pyrroles with Aryl Bromides
FULL PAPERS
2-(5-Formyl-1-methylpyrrol-2-yl)-benzonitrile (16): The
reaction of 2-bromobenzonitrile (0.182 g, 1 mmol), 1-methyl-
2-formylpyrrole (0.219 g, 2 mmol) and KOAc (0.196 g,
1-Methyl-5-pyridin-3-ylpyrrole-2-carbaldehyde
(21):[18]
The reaction of 3-bromopyridine (0.158 g, 1 mmol), 1-
methyl-2-formylpyrrole (0.219 g, 2 mmol) and KOAc
(0.196 g, 2 mmol) with PdACTHNUTRGNE(NUG OAc)2 (0.22 mg, 0.001 mmol) af-
2 mmol) with PdACHTUNGTRENNUNG(OAc)2 (0.22 mg, 0.001 mmol) affords the
fords the corresponding product 21; isolated yield: 0.149 g
(80%). H NMR (200 MHz, CDCl3): d=9.78 (s, 1H), 8.70
corresponding product 16; isolated yield: 0.166 g (79%).
1H NMR (200 MHz, CDCl3): d=9.65 (s, 1H), 7.82 (d, J=
8.0 Hz, 1H), 7.69 (d, J=8.0 Hz, 1H), 7.56 (t, J=7.5 Hz,
1H), 7.50 (t, J=7.5 Hz, 1H), 7.03 (d, J=4.1 Hz, 1H), 6.46
(d, J=4.1 Hz, 1H), 3.87 (s, 3H); 13C NMR (50 MHz,
CDCl3): d=180.0, 138.9, 134.5, 133.5, 133.3, 132.6, 131.0,
129.1, 123.8, 117.5, 113.3, 112.3, 34.1; anal. calcd. for
C13H10N2O: C 74.27, H 4.79; found: C 74.40, H 4.60.
1
(m, 2H), 7.72 (d, J=7.5 Hz, 1H), 7.40 (dd, J=7.5 and
4.2 Hz, 1H), 6.98 (d, J=3.9 Hz, 1H), 6.33 (d, J=3.9 Hz,
1H), 3.87 (s, 3H).
1-Methyl-5-pyridin-4-ylpyrrole-2-carbaldehyde (22): The
reaction of 4-bromopyridine hydrochloride (0.194 g,
1 mmol), 1-methyl-2-formylpyrrole (0.219 g, 2 mmol) and
KOAc (0.294 g, 3 mmol) with PdACTHNUTRGNEUNG(OAc)2 (1.1 mg,
5-(2-Formylphenyl)-1-methylpyrrole-2-carbaldehyde (17):
The reaction of 2-bromobenzaldehyde (0.187 g, 1 mmol), 1-
methyl-2-formylpyrrole (0.219 g, 2 mmol) and KOAc
0.005 mmol) affords the corresponding product 22; isolated
1
yield: 0.130 g (70%). H NMR (200 MHz, CDCl3): d=9.62
(s, 1H), 8.70 (d, J=6.0 Hz, 2H), 7.34 (d, J=6.5 Hz, 2H),
6.99 (d, J=3.9 Hz, 1H), 6.40 (d, J=3.9 Hz, 1H), 3.97 (s,
3H); 13C NMR (50 MHz, CDCl3): d=179.9, 150.1, 140.7,
138.6, 133.9, 124.1, 123.2, 111.5, 34.4; anal. calcd. for
C11H10N2O: C, 70.95; H, 5.41; found: C, 70.80; H, 5.57.
1-Methyl-5-quinolin-3-ylpyrrole-2-carbaldehyde (23): The
reaction of 3-bromoquinoline (0.208 g, 1 mmol), 1-methyl-2-
formylpyrrole (0.219 g, 2 mmol) and KOAc (0.196 g,
(0.196 g, 2 mmol) with PdACTHNUTRGNE(NUG OAc)2 (0.22 mg, 0.001 mmol) af-
fords the corresponding product 17; isolated yield: 0.147 g
1
(69%). H NMR (200 MHz, CDCl3): d=9.88 (s, 1H), 9.64 (s,
1H), 8.06 (d, J=8.0 Hz, 1H), 7.70–7.45 (m, 2H), 7.42 (d, J=
8.0 Hz, 1H), 7.03 (d, J=4.1 Hz, 1H), 6.30 (d, J=4.1 Hz,
1H), 3.87 (s, 3H); 13C NMR (50 MHz, CDCl3): d=191.0,
179.9, 139.0, 135.2, 133.9, 133.8, 133.1, 131.5, 129.6, 128.4,
123.8, 113.1, 34.0; anal. calcd. for C13H11NO2: C 73.22, H
5.20; found: C 73.40, H 5.34.
2 mmol) with PdACTHNUTRGNEUNG(OAc)2 (0.22 mg, 0.001 mmol) affords the
corresponding product 23; isolated yield: 0.184 g (78%).
1H NMR (200 MHz, CDCl3): d=9.62 (s, 1H), 8.98 (s, 1H),
8.19 (s, 1H), 8.16 (d, J=8.0 Hz, 1H), 7.87 (d, J=8.0 Hz,
1H), 7.77 (t, J=7.8 Hz, 1H), 7.60 (t, J=7.8 Hz, 1H), 7.03
(d, J=4.1 Hz, 1H), 6.42 (d, J=4.1 Hz, 1H), 3.99 (s, 3H);
13C NMR (50 MHz, CDCl3): d=179.9, 150.3, 147.6, 140.5,
135.8, 133.7, 130.4, 129.4, 128.0, 127.5, 127.3, 124.4, 124.3,
111.7, 34.5; anal. calcd. for C15H12N2O: C 76.25 H 5.12;
found: C 76.40, H 5.23.
5-(2,4-Difluorophenyl)-1-methylpyrrole-2-carbaldehyde
(18): The reaction of 1-bromo-2,4-difluorobenzene (0.193 g,
1 mmol), 1-methyl-2-formylpyrrole (0.219 g, 2 mmol) and
K2CO3 (0.278 g, 2 mmol) with PdACTHUNGRTNE(NUG OAc)2 (1.1 mg,
0.005 mmol) affords the corresponding product 18; isolated
1
yield: 0.120 g (54%). H NMR (200 MHz, CDCl3): d=9.61
(s, 1H), 7.45–7.15 (m, 1H), 7.10–6.95 (m, 3H), 6.30 (d, J=
4.1 Hz, 1H), 3.84 (s, 3H); 13C NMR (50 MHz, CDCl3): d=
179.7, 165.2 (d, J=252.4 Hz), 165.1 (d, J=250.4 Hz), 137.0,
133.1, 132.9 (dd, J=9.6 and 4.2 Hz), 123.9, 115.3 (d, J=
15.5 Hz), 111.9 (dd, J=11.7 and 3.5 Hz), 111.7, 104.0 (dd,
J=26.8 and 25.6 Hz), 34.0; anal. calcd. for C12H9F2NO: C
65.16, H 4.10; found: C 65.00, H 4.24.
5-(2-Fluorophenyl)-1-methylpyrrole-2-carbaldehyde (19):
The reaction of 2-bromofluorobenzene (0.175 g, 1 mmol), 1-
methyl-2-formylpyrrole (0.219 g, 2 mmol) and K2CO3
5-(4-Trifluoromethylphenyl)-1-methyl-2-acetylpyrrole
(24): The reaction of 4-trifluoromethylbromobenzene
(0.225 g,
1 mmol),
1-methyl-2-acetylpyrrole
(0.247 g,
2 mmol) and KOAc (0.196 g, 2 mmol) with PdACHTUNGTRENNUNG
(OAc)2
(1.1 mg, 0.005 mmol) affords the corresponding product 24;
1
isolated yield: 0.176 g (66%). H NMR (200 MHz, CDCl3):
d=7.71 (d, J=8.0 Hz, 2H), 7.52 (d, J=8.0 Hz, 2H), 7.04 (d,
J=4.1 Hz, 1H), 6.27 (d, J=4.1 Hz, 1H), 3.80 (s, 3H), 2.49
(s, 3H); 13C NMR (50 MHz, CDCl3): d=188.8, 141.0, 135.3,
132.5, 130.4 (q, J=32.5 Hz), 129.5, 125.7 (q, J=272.5 Hz),
125.5 (q, J=3.8 Hz), 119.6, 109.9, 35.2, 27.4; anal. calcd. for
C14H12F3NO: C 62.92, H 4.53; found: C 62.87, H 4.65.
4-(5-Acetyl-1-methylpyrrol-2-yl)-benzonitrile (25): The re-
action of 4-bromobenzonitrile (0.182 g, 1 mmol), 1-methyl-2-
acetylpyrrole (0.247 g, 2 mmol) and KOAc (0.196 g, 2 mmol)
(0.278 g, 2 mmol) with PdACTHNUTRGNE(UNG OAc)2 (1.1 mg, 0.005 mmol) af-
fords the corresponding product 19; isolated yield: 0.140 g
1
(69%). H NMR (200 MHz, CDCl3): d=9.62 (s, 1H), 7.60–
7.10 (m, 4H), 7.02 (d, J=4.1 Hz, 1H), 6.33 (d, J=4.1 Hz,
1H), 3.86 (s, 3H); 13C NMR (50 MHz, CDCl3): d=179.7,
159.7 (d, J=249.0 Hz), 138.1, 133.0, 132.0, 131.1 (d, J=
8.3 Hz), 124.4, 124.1, 119.0 (d, J=15.3 Hz), 116.1 (d, J=
22.0 Hz), 111.7, 34.1; anal. calcd. for C12H10FNO: C 70.93, H
4.96; found: C 71.04, H 4.87.
1-Methyl-5-naphthalen-1-ylpyrrole-2-carbaldehyde (20):
The reaction of 1-bromonaphthalene (0.207 g, 1 mmol), 1-
methyl-2-formylpyrrole (0.219 g, 2 mmol) and KOAc
with PdACHTUNTGRNE(UNG OAc)2 (1.1 mg, 0.005 mmol) affords the correspond-
ing product 25; isolated yield: 0.182 g (81%). 1H NMR
(200 MHz, CDCl3): d=7.62 (d, J=8.0 Hz, 2H), 7.43 (d, J=
8.0 Hz, 2H), 6.94 (d, J=4.1 Hz, 1H), 6.20 (d, J=4.1 Hz,
1H), 3.78 (s, 3H), 2.35 (s, 3H); 13C NMR (50 MHz, CDCl3):
d=188.2, 139.9, 135.6, 132.4, 131.8, 129.2, 119.2, 118.0, 111.0,
109.9, 34.8, 26.9; anal. calcd. for C14H12N2O: C 74.98, H
5.39; found: C 74.90, H 5.54.
(0.196 g, 2 mmol) with PdACTHNUTRGNE(NUG OAc)2 (0.22 mg, 0.001 mmol) af-
fords the corresponding product 20; isolated yield: 0.181 g
1
(77%). H NMR (200 MHz, CDCl3): d=9.70 (s, 1H), 8.03–
7.95 (m, 2H), 7.65–7.40 (m, 5H), 7.12 (d, J=4.1 Hz, 1H),
6.40 (d, J=4.1 Hz, 1H), 3.73 (s, 3H); 13C NMR (50 MHz,
CDCl3): d=179.4, 142.3, 133.4, 132.4, 132.2, 129.4, 128.5,
128.3, 128.2, 126.8, 126.2, 125.3, 125.0, 124.1, 111.9, 33.9;
anal. calcd. for C16H13NO: C 81.68, H 5.57; found: C 81.58,
H 5.70.
5-(4-Fluorophenyl)-1-methyl-2-acetylpyrrole (26): The re-
action of 4-bromofluorobenzene (0.175 g, 1 mmol), 1-
methyl-2-acetylpyrrole (0.247 g, 2 mmol) and KOAc
(0.196 g, 2 mmol) with PdACTHNUTRGNE(NUG OAc)2 (0.22 mg, 0.001 mmol) af-
fords the corresponding product 26; isolated yield: 0.174 g
1
(80%). H NMR (200 MHz, CDCl3): d=7.38 (dd, J=8.5 and
Adv. Synth. Catal. 2009, 351, 1977 – 1990
ꢁ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
1987

Julien Roger and Henri Doucet
FULL PAPERS
5.9 Hz, 2H), 7.14 (t, J=8.5 Hz, 2H), 7.02 (d, J=4.1 Hz,
1H), 6.18 (d, J=4.1 Hz, 1H), 3.85 (s, 3H), 2.47 (s, 3H);
13C NMR (50 MHz, CDCl3): d=188.5, 164.3 (d, J=
248.5 Hz), 141.7, 131.9, 131.1 (d, J=8.2 Hz), 127.8 (m),
119.6, 115.7 (d, J=21.7 Hz), 109.2, 35.0, 27.3; anal. calcd. for
C13H12FNO: C 71.87, H 5.57; found: C 71.89, H 5.60.
5-(4-Tolyl)-1-methyl-2-acetylpyrrole (27): The reaction of
4-bromotoluene (0.171 g, 1 mmol), 1-methyl-2-acetylpyrrole
(0.247 g, 2 mmol) and K2CO3 (0.278 g, 2 mmol) with
35.0, 27.3; anal. calcd. for C14H12N2O: C 74.98, H 5.39;
found: C 75.04, H 5.47.
2-(5-Acetyl-1-methylpyrrol-2-yl)-benzonitrile (32): The re-
action of 2-bromobenzonitrile (0.182 g, 1 mmol), 1-methyl-2-
acetylpyrrole (0.247 g, 2 mmol) and KOAc (0.196 g, 2 mmol)
with PdACHTNUGETRN(UNNG OAc)2 (0.22 mg, 0.001 mmol) affords the corre-
1
sponding product 32; isolated yield: 0.157 g (70%). H NMR
(200 MHz, CDCl3): d=7.76 (d, J=7.8 Hz, 1H), 7.64 (t, J=
7.5 Hz, 1H), 7.51 (t, J=7.5 Hz, 1H), 7.44 (d, J=8.0 Hz,
1H), 7.04 (d, J=4.1 Hz, 1H), 6.35 (d, J=4.1 Hz, 1H), 3.80
(s, 3H), 2.46 (s, 3H); 13C NMR (50 MHz, CDCl3): d=188.6,
137.5, 135.1, 133.3, 132.4, 132.2, 131.0, 128.7, 119.1, 117.3,
113.3, 110.8, 34.8, 27.3; anal. calcd. for C14H12N2O: C 74.98,
H 5.39; found: C 74.84, H 5.60.
PdACHTUNGTRENNUNG(OAc)2 (1.1 mg, 0.005 mmol) affords the corresponding
product 27; isolated yield: 0.156 g (73%). 1H NMR
(200 MHz, CDCl3): d=7.40–7.20 (m, 4H), 7.06 (d, J=
4.1 Hz, 1H), 6.22 (d, J=4.1 Hz, 1H), 3.92 (s, 3H), 2.50 (s,
3H), 2.44 (s, 3H); 13C NMR (50 MHz, CDCl3): d=187.9,
142.6, 137.8, 131.3, 128.8, 128.7, 128.4, 119.3, 108.7, 34.7,
26.9, 20.9; anal. calcd. for C14H15NO: C 78.84, H 7.09;
found: C 78.80, H 7.14.
5-(2-Tolyl)-1-methyl-2-acetylpyrrole (33): The reaction of
2-bromotoluene (0.171 g, 1 mmol), 1-methyl-2-acetylpyrrole
(0.247 g, 2 mmol) and KOAc (0.196 g, 2 mmol) with
PdACTHUNTRGENNG(U OAc)2 (1.1 mg, 0.005 mmol) affords the corresponding
5-(4-tert-Butylphenyl)-1-methyl-2-acetylpyrrole (28): The
reaction of 4-tert-butylbromobenzene (0.213 g, 1 mmol), 1-
methyl-2-acetylpyrrole (0.247 g, 2 mmol) and K2CO3
product 33; isolated yield: 0.079 g (37%). 1H NMR
(200 MHz, CDCl3): d=7.50–7.20 (m, 4H), 7.06 (d, J=
4.1 Hz, 1H), 6.12 (d, J=4.1 Hz, 1H), 3.67 (s, 3H), 2.50 (s,
3H), 2.17 (s, 3H); 13C NMR (50 MHz, CDCl3): d=188.4,
142.1, 138.0, 131.6, 130.9, 130.7, 130.1, 128.9, 125.7, 119.4,
109.1, 34.4, 27.2, 19.8; anal. calcd. for C14H15NO: C 78.84, H
7.09; found: C 78.89, H 7.01.
(0.278 g, 2 mmol) with PdACTHNUTRGNE(UNG OAc)2 (1.1 mg, 0.005 mmol) af-
fords the corresponding product 28; isolated yield: 0.209 g
1
(82%). H NMR (200 MHz, CDCl3): d=7.50 (d, J=8.0 Hz,
2H), 7.37 (d, J=8.0 Hz, 2H), 7.06 (d, J=4.1 Hz, 1H), 6.23
(d, J=4.1 Hz, 1H), 3.93 (s, 3H), 2.50 (s, 3H), 1.39 (s, 9H);
13C NMR (50 MHz, CDCl3): d=188.2, 151.2, 142.9, 131.9,
128.8, 128.6, 125.3, 119.6, 109.0, 35.1, 35.0, 31.1, 27.2; anal.
calcd. for C17H21NO: C 79.96, H 8.29; found: C 79.84, H
8.24.
5-(4-Methoxyphenyl)-1-methyl-2-acetylpyrrole (29): The
reaction of 4-bromoanisole (0.187 g, 1 mmol), 1-methyl-2-
acetylpyrrole (0.247 g, 2 mmol) and K2CO3 (0.278 g,
1-(1-Methyl-5-naphthalen-1-ylpyrrol-2-yl)-ethanone (34):
The reaction of 1-bromonaphthalene (0.207 g, 1 mmol), 1-
methyl-2-acetylpyrrole (0.247 g, 2 mmol) and KOAc
(0.196 g, 2 mmol) with PdACTHNUTRGNE(UNG OAc)2 (1.1 mg, 0.005 mmol) af-
fords the corresponding product 34; isolated yield: 0.199 g
1
(80%). H NMR (200 MHz, CDCl3): d=8.00–7.83 (m, 2H),
7.65–7.40 (m, 5H), 7.17 (d, J=4.1 Hz, 1H), 6.32 (d, J=
4.1 Hz, 1H), 3.70 (s, 3H), 2.56 (s, 3H); 13C NMR (50 MHz,
CDCl3): d=188.4, 140.8, 133.4, 132.5, 131.3, 129.5, 129.2,
128.6, 128.3, 126.7, 126.1, 125.5, 125.0, 119.4, 110.4, 34.7,
27.2; anal. calcd. for C17H15NO: C 81.90, H 6.06; found: C
82.04, H 6.00.
2 mmol) with PdACHTUNGTRENNUNG(OAc)2 (1.1 mg, 0.005 mmol) affords the
corresponding product 29; isolated yield: 0.183 g (80%).
1H NMR (200 MHz, CDCl3): d=7.34 (d, J=8.3 Hz, 2H),
7.04 (d, J=4.1 Hz, 1H), 7.00 (d, J=8.3 Hz, 2H), 6.19 (d, J=
4.1 Hz, 1H), 3.89 (s, 3H), 3.87 (s, 3H), 2.48 (s, 3H);
13C NMR (50 MHz, CDCl3): d=188.0, 159.3, 142.5, 131.3,
130.0, 123.7, 119.4, 113.7, 108.6, 55.0, 34.8, 26.9; anal. calcd.
for C14H15NO2: C 73.34, H 6.59; found: C 73.39, H 6.47.
5-(4-Dimethylaminophenyl)-1-methyl-2-acetylpyrrole
1-(1-Methyl-5-pyridin-3-ylpyrrol-2-yl)-ethanone
(35):[19]
The reaction of 3-bromopyridine (0.158 g, 1 mmol), 1-
methyl-2-acetylpyrrole (0.247 g, 2 mmol) and KOAc
(0.196 g, 2 mmol) with PdACTHNUTRGNE(UNG OAc)2 (1.1 mg, 0.005 mmol) af-
fords the corresponding product 35; isolated yield: 0.168 g
1
(30): The reaction of 4-bromo-N,N-dimethylaniline (0.200 g,
1 mmol), 1-methyl-2-acetylpyrrole (0.247 g, 2 mmol) and
K2CO3 (0.278 g, 2 mmol) with PdACTHUNGRTNE(NUG OAc)2 (1.1 mg,
(84%). H NMR (200 MHz, CDCl3): d=8.65 (m, 2H), 7.70
(d, J=7.2 Hz, 1H), 7.38 (dd, J=7.2 and 4.2 Hz, 1H), 7.03
(d, J=4.2 Hz, 1H), 6.26 (d, J=4.2 Hz, 1H), 3.87 (s, 3H),
2.47 (s, 3H).
Methyl 5-(4-cyanophenyl)-1-methylpyrrole-2-carboxylate
(36): The reaction of 4-bromobenzonitrile (0.182 g, 1 mmol),
methyl 1-methyl-2-pyrrolecarboxylate (0.278 g, 2 mmol) and
0.005 mmol) affords the corresponding product 30; isolated
1
yield: 0.179 g (74%). H NMR (200 MHz, CDCl3): d=7.50
(d, J=8.3 Hz, 2H), 7.36 (d, J=8.3 Hz, 2H), 7.06 (d, J=
4.1 Hz, 1H), 6.23 (d, J=4.1 Hz, 1H), 3.93 (s, 3H), 2.50 (s,
3H), 1.38 (s, 6H); 13C NMR (50 MHz, CDCl3): d=187.5,
149.8, 143.5, 130.9, 129.7, 119.5, 118.7, 111.5, 106.1, 39.9,
34.7, 26.8; anal. calcd. for C15H18N2O: C 74.35, H 7.49;
found: C 74.30, H 7.43.
3-(5-Acetyl-1-methylpyrrol-2-yl)-benzonitrile (31): The re-
action of 3-bromobenzonitrile (0.182 g, 1 mmol), 1-methyl-2-
acetylpyrrole (0.247 g, 2 mmol) and KOAc (0.196 g, 2 mmol)
KOAc (0.196 g, 2 mmol) with PdACTHNUTRGNEUNG(OAc)2 (0.22 mg,
0.001 mmol) affords the corresponding product 36; isolated
1
yield: 0.200 g (83%). H NMR (200 MHz, CDCl3): d=7.65
(d, J=8.0 Hz, 2H), 7.44 (d, J=8.0 Hz, 2H), 6.95 (d, J=
4.1 Hz, 1H), 6.20 (d, J=4.1 Hz, 1H), 3.83 (s, 3H), 3.78 (s,
3H); 13C NMR (50 MHz, CDCl3): d=161.5, 139.1, 136.4,
132.2, 129.4, 124.7, 118.4, 117.6, 111.3, 110.2, 51.1, 34.4; anal.
calcd. for C14H12N2O2: C 69.99, H 5.03; found: C 70.11, H
4.87.
Methyl 1-methyl-5-(4-propionylphenyl)-pyrrole-2-carbox-
ylate (37): The reaction of 4-bromopropiophenone (0.214 g,
1 mmol), methyl 1-methyl-2-pyrrolecarboxylate (0.278 g,
with PdACHTUNGTRENNUNG(OAc)2 (0.22 mg, 0.001 mmol) affords the corre-
1
sponding product 31; isolated yield: 0.186 g (83%). H NMR
(200 MHz, CDCl3): d=7.75–7.55 (m, 4H), 7.01 (d, J=
4.1 Hz, 1H), 6.23 (d, J=4.1 Hz, 1H), 3.85 (s, 3H), 2.45 (s,
3H); 13C NMR (50 MHz, CDCl3): d=188.6, 139.7, 133.2,
132.9, 132.4, 132.3, 131.4, 129.3, 119.4, 118.1, 112.8, 109.9,
2 mmol) and KOAc (0.196 g, 2 mmol) with PdACHTUNGTRENNUNG(OAc)2
1988
asc.wiley-vch.de
ꢁ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2009, 351, 1977 – 1990

Regioselective C-2 or C-5 Direct Arylation of Pyrroles with Aryl Bromides
FULL PAPERS
(0.22 mg, 0.001 mmol) affords the corresponding product 37;
isolated yield: 0.217 g (80%). H NMR (200 MHz, CDCl3):
product 43; isolated yield: (0.175 g (70%). 1H NMR
(200 MHz, CDCl3): d=7.50–7.15 (m, 5H), 7.10 (d, J=
8.4 Hz, 2H), 6.95 (m, 1H), 6.81 (d, J=8.4 Hz, 2H), 6.40 (m,
2H), 3.81 (s, 3H).
1
d=8.03 (d, J=8.3 Hz, 2H), 7.50 (d, J=8.3 Hz, 2H), 7.03 (d,
J=4.1 Hz, 1H), 6.27 (d, J=4.1 Hz, 1H), 3.91 (s, 3H), 3.85
(s, 3H), 3.03 (q, J=7.5 Hz, 2H), 1.25 (t, J=7.5 Hz, 3H);
13C NMR (50 MHz, CDCl3): d=199.9, 161.6, 140.2, 136.3,
135.9, 129.1, 128.1, 124.2, 117.7, 109.8, 51.0, 34.5, 31.7, 8.1;
anal. calcd. for C16H17N2O3: C 70.83, H 6.32; found: C 70.68,
H 6.40.
Methyl 1-methyl-5-p-tolylpyrrole-2-carboxylate (38): The
reaction of 4-bromotoluene (0.171 g, 1 mmol), methyl 1-
methyl-2-pyrrolecarboxylate (0.278 g, 2 mmol) and KOAc
2-(4-Methylphenyl)-1-phenylpyrrole (44):[22] The reaction
of 4-bromotoluene (0.171 g, 1 mmol), 1-phenylpyrrole
(0.536 g, 4 mmol) and KOAc (0.196 g, 2 mmol) with
PdACTHNUGTRENNG(U OAc)2 (0.22 mg, 0.001 mmol) affords the corresponding
product 44; isolated yield: 0.170 g (73%). 1H NMR
(200 MHz, CDCl3): d=7.50–6.90 (m, 10H), 6.52–6.35 (m,
2H), 2.35 (s, 3H).
2-(4-Cyanophenyl)-5-(3-pyridyl)-1-methylpyrrole
(45):
The reaction of 3-bromopyridine (0.158 g, 1 mmol), 2-(4-cya-
nophenyl)-1-methylpyrrole 39 (0.364 g, 2 mmol) and KOAc
(0.196 g, 2 mmol) with PdACTHNUTRGNE(NUG OAc)2 (0.22 mg, 0.001 mmol) af-
(0.196 g, 2 mmol) with PdACTHNUTRGNE(NUG OAc)2 (0.22 mg, 0.001 mmol) af-
fords the corresponding product 38; isolated yield: 0.120 g
1
(52%). H NMR (200 MHz, CDCl3): d=7.35–7.10 (m, 4H),
fords the corresponding product 45; isolated yield: 0.187 g
7.04 (d, J=4.1 Hz, 1H), 6.20 (d, J=4.1 Hz, 1H), 3.90 (s,
3H), 3.86 (s, 3H), 2.43 (s, 3H); 13C NMR (50 MHz, CDCl3):
d=161.7, 141.6, 137.7, 129.0, 128.9, 128.8, 122.9, 117.7, 108.7,
50.8, 34.1, 21.0; anal. calcd. for C14H15NO2: C 73.34, H 6.59;
found: C 73.10, H 6.62.
1
(72%). H NMR (200 MHz, CDCl3): d=8.75 (m, 1H), 8.58
(m, 1H), 7.77 (d, J=8.0 Hz, 1H), 7.71(d, J=8.4 Hz, 2H),
7.56 (d, J=8.4 Hz, 2H), 7.38 (m, 1H), 6.44 (m, 1H), 6.40
(m, 1H), 3.64 (s, 3H); 13C NMR (50 MHz, CDCl3): d=
149.4, 148.3, 137.6, 135.9, 135.7, 135.0, 132.3, 128.5, 123.6,
118.9, 111.0, 110.4, 110.1, 34.5; anal. calcd. for C17H13N3: C
78.74, H 5.05; found: C 78.80, H 5.14.
2-(4-Cyanophenyl)-1-methylpyrrole (39):[20] The reaction
of 4-bromobenzonitrile (0.182 g, 1 mmol), 1-methylpyrrole
(0.324 g, 4 mmol) and KOAc (0.196 g, 2 mmol) with
2-(4-Acetylphenyl)-1-methylindole (46):[11a] The reaction
of 4-bromoacetophenone (0.200 g, 1 mmol), 1-methylindole
(0.262 g, 2 mmol) and K2CO3 (0.278 g, 2 mmol) with
PdACHTUNGTRENNUNG(OAc)2 (0.022 mg, 0.0001 mmol) affords the correspond-
ing product 39; isolated yield: 0.146 g (80%). 1H NMR
(200 MHz, CDCl3): d=7.69 (d, J=8.0 Hz, 2H), 7.52 (d, J=
8.0 Hz, 2H), 6.81 (m, 1H), 6.37 (m, 1H), 6.26 (m, 1H), 3.74
(s, 3H).
PdACTHNUGTRENNG(U OAc)2 (0.22 mg, 0.001 mmol) affords the corresponding
product 46; isolated yield: 0.195 g (78%). 1H NMR
(200 MHz, CDCl3): d=8.10 (d, J=8.3 Hz, 2H), 7.80–7.60
(m, 3H), 7.50–7.10 (m, 3H), 6.69 (s, 1H), 3.85 (s, 3H), 2.70
(s, 3H).
2-(4-Methoxyphenyl)-1-methylpyrrole (40):[21] The reac-
tion of 4-bromoanisole (0.187 g, 1 mmol), 1-methylpyrrole
(0.324 g, 4 mmol) and KOAc (0.196 g, 2 mmol) with
PdACHTUNGTRENNUNG(OAc)2 (0.22 mg, 0.001 mmol) affords the corresponding
product 40; isolated yield: 0.131 g (70%). 1H NMR
(200 MHz, CDCl3): d=7.37 (d, J=8.6 Hz, 2H), 7.00 (d, J=
8.6 Hz, 2H), 6.75 (m, 1H), 6.23 (m, 2H), 3.89 (s, 3H), 3.68
(s, 3H).
2-(4-Cyanophenyl)-1-phenylpyrrole (41): The reaction of
4-bromobenzonitrile (0.182 g, 1 mmol), 1-phenylpyrrole
(0.536 g, 4 mmol) and KOAc (0.196 g, 2 mmol) with
Acknowledgements
J. R. is grateful to “Ministꢀre de l’enseignement supꢁrieur”
for a grant. We thank the Centre National de la Recherche
Scientifique and “Rennes Metropole” for providing financial
support.
PdACHTUNGTRENNUNG(OAc)2 (0.022 mg, 0.0001 mmol) affords the correspond-
ing product 41; isolated yield: 0.191 g (78%). 1H NMR
(200 MHz, CDCl3): d=7.49 (d, J=8.0 Hz, 2H), 7.45–7.35
(m, 3H), 7.30–7.15 (m, 4H), 7.02 (m, 1H), 6.60 (m, 1H),
6.43 (m, 1H); 13C NMR (50 MHz, CDCl3): d=139.7, 137.1,
131.8, 131.6, 129.2, 127.8, 127.2, 126.3, 125.6, 118.9, 112.6,
109.8, 109.1; anal. calcd. for C17H12N2: C 83.58, H 4.95;
found: C 83.47, H 5.10.
2-(4-Acetylphenyl)-1-phenylpyrrole (42): The reaction of
4-bromoacetophenone (0.199 g, 1 mmol), 1-phenylpyrrole
(0.536 g, 4 mmol) and KOAc (0.196 g, 2 mmol) with
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ing product 42; isolated yield: 0.209 g (80%). 1H NMR
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125.7, 125.5, 112.1, 109.6; anal. calcd. for C18H15NO: C
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PdACHTUNGTRENNUNG(OAc)2 (0.22 mg, 0.001 mmol) affords the corresponding
Adv. Synth. Catal. 2009, 351, 1977 – 1990
ꢁ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
1989

Julien Roger and Henri Doucet
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Adv. Synth. Catal. 2009, 351, 1977 – 1990