Palladium-catalysed direct arylations of NH-free pyrrole and N-tosylpyrrole with aryl bromides

Article abstract of DOI:10.1016/j.tetlet.2011.11.081

The palladium-catalysed direct coupling of aryl halides with pyrroles provides a greener access to arylated pyrroles than more classical couplings such as Suzuki, Stille or Negishi reactions. However, so far, NH-free pyrrole and N-tosylpyrrole gave disappointing results for such couplings either in terms of regioselectivity of the arylation, catalyst loading or substrate scope. The reactivity of both NH-free pyrrole and N-tosylpyrrole was studied, and the tosylated pyrrole led to higher yields of coupling products due to better conversions of the aryl bromides. A range of aryl bromides undergo regioselective coupling at C2 of N-tosylpyrrole in moderate to good yields using 1 mol % [Pd(Cl(C₃H₅)]₂ as the catalyst, KOAc as the base in DMAc.

Full text of DOI:10.1016/j.tetlet.2011.11.081

Tetrahedron Letters 53 (2012) 509–513
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Tetrahedron Letters
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Palladium-catalysed direct arylations of NH-free pyrrole and N-tosylpyrrole
with aryl bromides
Charles Beromeo Bheeter a, Jitendra K. Bera b, Henri Doucet a,
⇑
a Institut Sciences Chimiques de Rennes, UMR 6226 CNRS-Université de Rennes ‘Catalyse et Organometalliques’, Campus de Beaulieu, 35042 Rennes, France
b Department of Chemistry, Indian Institute of Technology Kanpur, 208 016 Kanpur, India
a r t i c l e i n f o
a b s t r a c t
Article history:
The palladium-catalysed direct coupling of aryl halides with pyrroles provides a greener access to
arylated pyrroles than more classical couplings such as Suzuki, Stille or Negishi reactions. However, so
far, NH-free pyrrole and N-tosylpyrrole gave disappointing results for such couplings either in terms of
regioselectivity of the arylation, catalyst loading or substrate scope. The reactivity of both NH-free pyrrole
and N-tosylpyrrole was studied, and the tosylated pyrrole led to higher yields of coupling products due to
better conversions of the aryl bromides. A range of aryl bromides undergo regioselective coupling at C2 of
N-tosylpyrrole in moderate to good yields using 1 mol % [Pd(Cl(C3H5)]2 as the catalyst, KOAc as the base
in DMAc.
Received 5 October 2011
Revised 8 November 2011
Accepted 15 November 2011
Available online 22 November 2011
Keywords:
Pyrroles
Aryl bromides
C–H activation
Catalysis
Ó 2011 Elsevier Ltd. All rights reserved.
Palladium
The arylation of pyrroles is an important field of research in
organic synthesis due to their biological or physical properties.1
The direct regioselective couplings at C2 or C5 of 1-alkyl- or 1-aryl-
pyrroles with aryl halides via palladium-catalysed C–H bond
activation/functionalisation2–4 provides a cost-effective and envi-
ronmentally attractive access to arylpyrroles.5 The direct arylation
of NH-free indoles has also been reported.6 On the other hand, the
direct arylation of NH-free pyrroles has attracted less attention
due to the poor reactivity of this substrate.7–9 Some of these cou-
plings employed metal pyrrolyl salts as reactants.7 The use of such
salts allows a high regiocontrol of the arylation, but produces a
metallic salt as waste. In the absence of metallic salts, high catalyst
loadings were employed, and low regioselectivities and/or yields
were generally obtained.8 For example, Ohta and co-workers have
reported the direct arylation of pyrrole with chloropyrazines.8a
However, the 2-arylpyrroles were isolated in only 25–29% yield.
The coupling reaction of 3-bromopyridine with pyrrole, using
PdCl2[P(o-Tol)3]2/Binap as the catalytic system, gave a mixture of
2-pyridylpyrrole and N-pyridylpyrrole in 46% and 21% yields,
respectively.8b Sames and co-workers have reported the direct
5-arylation of methyl pyrrole-2-carboxylate with iodobenzene
using 5 mol % of Pd(OAc)2 as the catalyst.8c Again, the target prod-
uct was obtained in a low yield of 30%. Recently the regioselective
C2 arylation of pyrrole using 10 mol % of Pd(OH)2/C has been repor-
ted.8d However, the reaction proceeds only with aryl iodides, which
are known to be very reactive, but expensive substrates. Moreover
for many substrates, only moderate yields had been obtained.
Similarly, only a few results using N-tosylpyrrole have been
reported so far.8a,10,11 In 1992, Ohta and co-workers described
the direct arylation of N-phenylsulfonylpyrrole using 3,6-dialkyl-
2-chloropyrazines as coupling partners.8a In the course of these
reactions, mixtures of 2- and 3-arylated pyrroles were obtained
(ratios C2:C3 arylation from 1:1 to 2:5). On the other hand, a reac-
tion between 1-tosylpyrrole and iodobenzene using 5 mol % of an
iridium-catalyst and Ag2CO3 as the base gave regioselectively the
C2 arylated pyrrole in 31% yield.10
In summary, N-alkyl or N-aryl pyrroles have been largely em-
ployed for palladium-catalysed direct arylation; on the other hand,
NH-free pyrroles display a poor reactivity. This might be due to the
poisoning of palladium by coordination of pyrrole. An alternative
reagent to NH-free pyrrole could be N-tosylpyrrole as its deprotec-
tion into NH-free pyrrole is well known.12 However, so far, the
reactivity and especially the regioselectivities (C2 vs C3 aryla-
tion)8a of this reagent for direct arylation remain unclear, and need
to be largely improved in order to provide an attractive and indus-
trially viable access to NH-free arylated pyrroles.
Here, we wish to report on the regioselectivity and reactivity of
NH-free, N-tosyl-, N-mesyl-, and N-methylpyrroles in the presence
of a phosphine-free palladium catalyst. The scope of the direct
arylation of N-tosylpyrrole with a variety of aryl bromides is also
examined.
First, we compared the reactivity of NH-free pyrrole and
N-tosylpyrrole (Scheme 1). In the presence of 1 mol % Pd(OAc)2
as the catalyst, KOAc as the base and 4-bromobenzonitrile as the
⇑
Corresponding author. Tel.: +33 2 23 23 63 84; fax: +33 2 23 23 69 39.
E-mail address: henri.doucet@univ-rennes1.fr (H. Doucet).
0040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2011.11.081

510
C. B. Bheeter et al. / Tetrahedron Letters 53 (2012) 509–513
[Pd]
Br
CN
+
N
R
N
base
CN
R
R = H: 1
R=Ts:
2
Scheme 1. Coupling of pyrrole or 1-(toluene-4-sulfonyl)pyrrole with 4-bromobenzonitrile.
coupling partner, low yields in 1 or 2 were obtained with both
pyrroles (Table 1, entries 1 and 2). However, in both cases, a regio-
selective arylation at C2 was observed. No formation of C3 arylated
pyrroles was detected. On the other hand, in the presence of
1 mol % [PdCl(C3H5)]2 as the catalyst, a better yield in 2 was ob-
tained (Table 1, entries 3 and 4). Then, we examined a few other
reaction conditions using N-tosylpyrrole as the reactant. In the
presence of K2CO3, Cs2CO3 or K3PO4, no formation of the target
compound 2 was detected, and lower yields were obtained with
CsOAc or NaOAc (Table 1, entries 5–9). The use of some phosphine
ligands did not improve the yields of 2 (Table 1, entries 10–13).
Then, we performed a reaction at 150 °C instead of 130 °C. How-
ever, at this temperature, in the presence of KOAc as the base,
DMAc as the solvent and 1 mol % [PdCl(C3H5)]2 as the catalyst, 2
was obtained in a lower yield of 30% (Table 1, entry 14). Low yields
of 2 were also obtained in the presence of NMP or DMF as the sol-
vent (Table 1, entries 15 and 16). Finally, the use of 4-chlorobenzo-
nitrile instead of 4-bromobenzonitrile as the coupling partner gave
no trace of 2 (Table 1, entry 17).
Table 1
Influence of the reaction conditions for palladium-catalysed direct arylation of pyrrole
or 1-(toluene-4-sulfonyl)pyrrole with 4-bromobenzonitrile (Scheme 1)
Entry
R
Catalyst
Solvent
Base
Yield in 2 (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
Ts
H
Ts
H
Pd(OAc)2
Pd(OAc)2
DMAc
DMAc
DMAc
DMAc
DMAc
DMAc
DMAc
DMAc
DMAc
DMAc
DMAc
DMAc
DMAc
DMAc
NMP
KOAc
KOAc
KOAc
KOAc
K2CO3
K3PO4
Cs2CO3
CsOAc
NaOAc
KOAc
KOAc
KOAc
KOAc
KOAc
KOAc
KOAc
KOAc
14
16
75
51
0
[PdCl(C3H5)]2
[PdCl(C3H5)]2
[PdCl(C3H5)]2
[PdCl(C3H5)]2
[PdCl(C3H5)]2
[PdCl(C3H5)]2
[PdCl(C3H5)]2
Pd(OAc)2/dppb
Pd(OAc)2/dppe
Pd(OAc)2/2 PPh3
PdCl(C3H5)(dppb)
[PdCl(C3H5)]2
[PdCl(C3H5)]2
[PdCl(C3H5)]2
[PdCl(C3H5)]2
Ts
Ts
Ts
Ts
Ts
Ts
Ts
Ts
Ts
Ts
Ts
Ts
Ts
0
0
50
32
50
12
55
37
30a
22
26
0b
DMF
DMAc
Conditions: catalyst (0.01 equiv), 4-bromobenzonitrile (1 equiv), N-tosylpyrrole
(1.5 equiv), base (2 equiv), 130 °C, 20 h, under argon.
Then, we employed N-mesylpyrrole and 4-bromobenzonitrile
as coupling partners (Scheme 2). However, this pyrrole, in the pres-
ence of 1 mol % [PdCl(C3H5)]2 as the catalyst at 130 °C, led to a mix-
ture of NH-free pyrrole and biphenyl-4,40-dicarbonitrile; whereas,
a
Reaction temp 150 °C.
b
4-Chlorobenzonitrile instead of 4-bromobenzonitrile.
[PdCl(C3H5)]2 1 mol%
+
Br
CN
N
N
DMAc, KOAc,
130 °C, 20 h
CN
Ms
Ms
3
Scheme 2. Attempt of coupling of N-mesylpyrrole with 4-bromobenzonitrile.
N
H
N
[PdCl(C3H5)]2 1 mol%
H
CN
CN
2 equiv.
1 38%
2 2%
Br
CN
+
DMAc, KOAc,
130 °C, 20 h
1 equiv.
N
N
Ts
Ts
2 equiv.
Scheme 3. Competitive experiment using a mixture of pyrrole and 1-(toluene-4-sulfonyl)pyrrole.
N
N
[PdCl(C3H5)]2 1 mol%
CN
CN
Br
CN
+
2 equiv.
4 67%
2 2%
DMAc, KOAc,
130 °C, 20 h
1 equiv.
N
N
Ts
2 equiv.
Ts
Scheme 4. Competitive experiment using a mixture of N-methylpyrrole and 1-(toluene-4-sulfonyl)pyrrole.

C. B. Bheeter et al. / Tetrahedron Letters 53 (2012) 509–513
511
exclusively the formation of product 1 (Scheme 3). However, only
a partial conversion of the aryl bromide was observed, and 1 was
obtained in only 38% yield. This result seems to indicate that the
coordination of NH-free pyrrole to palladium is faster than the
coordination of N-tosylpyrrole. This easier coordination might par-
tially poison the catalyst resulting in poor conversions of aryl
bromide.
[PdCl(C3H5)]2 1 mol%
R
Br
+
N
N
R
DMAc, KOAc,
130 °C, 20 h
Ts
Ts
1, 5-19
Scheme 5. Scope of the 2-arylation of 1-(toluene-4-sulfonyl)pyrrole.
A similar reaction performed using a mixture of N-methylpyrrole
and N-tosylpyrrole led almost exclusively to product 4 (Scheme 4).
This result was expected, as we had previously observed that with
the desired compound 3 was not detected. This pyrrole appears to
be unstable under these reaction conditions.
In order to have a better insight of the reactivity of NH-free and
N-tosylpyrrole for direct arylation, we performed a competitive
experiment using an equimolar mixture of these two reactants in
the presence of 4-bromobenzonitrile. We observed almost
N-methylpyrrole,
a substrate/catalyst ratio of 1000 could be
employed for the direct arylation with 4-bromobenzonitrile.5c
Therefore, when there is no need of an NH-free function on pyrrole
after the arylation step, 1-alkylpyrroles should be preferred to both
NH-free and N-tosylpyrrole for the direct arylations.
As the tosyl substituent on nitrogen appears to be the best pro-
tecting group for pyrrole, we examined the scope of the reaction of
N-tosylpyrrole with a variety of aryl bromides (Scheme 5, Tables 2
and 3). The reaction of other para-substituted electron-deficient aryl
bromides such as 4-bromobenzaldehyde, 4-bromopropiophenone,
methyl 4-bromobenzoate or 4-trifluoromethylbromobenzene with
N-tosylpyrrole gave the expected products 5–8 in 55–64% yields
(Table 2, entries 1–5). Surprisingly, even the deactivated aryl
bromides, 4-tert-butylbromobenzene and 4-bromotoluene gave
the desired coupling products 11 and 12 in relatively good yields
(Table 2, entries 7 and 8). It should be noted that the use of
4-iodotoluene instead of 4-bromotoluene led to a lower yield of 12
(Table 2, entry 9). As expected, the meta-substituted aryl bromide,
3-bromobenzonitrile, also gave the target compound 13 in good
yield (Table 2, entry 10). The ortho-substituents on aryl halides gen-
erally have a more important influence on the yields of palladium-
catalysed reactions due to their steric and/or coordination
Table 2
Palladium-catalysed 2-arylation of 1-(toluene-4-sulfonyl)pyrrole (Scheme 5)14,15
Entry Aryl bromide
Product
Yield
(%)
O
O
O
O
Br
1
62
61
63
N
5
6
Ts
Br
2
N
Ts
O
O
Br
3
N
OMe
OMe
Ts
7
Br
CF3
CF3
Table 3
4
55
64
62
41
N
Palladium-catalysed 2-arylation of 1-(toluene-4-sulfonyl)pyrrole with heteroaryl
bromides (Scheme 5)14,15
Ts
8
Entry
1
Aryl bromide
Product
Yield (%)
40
Br
F
F
5
N
Br
Ts
9
N
N
N
Ts
15
Br
Cl
Cl
6
N
Br
Br
N, HCl
N
Ts
10
2
3
58
40
N
Ts
16
Br
7
N
Ts
11
8
9
47
N
N
N
N
N
19a
Br
Ts
17
N
Ts
12
Br
4
5
47
46
Br
Br
10
68
60
N
N
CN
CN
Ts
13
Ts
18
19
N
N
N
N
Br
11
N
N
NC
NC
Ts
14
Ts
Conditions: [PdCl(C3H5)]2 (0.01 mmol), aryl bromide (1 mmol), 1-(toluene-4-
sulfonyl)pyrrole (1.5 mmol), KOAc (3 mmol.), DMAc (5 mL), 20 h, 130 °C, isolated
yields.
Conditions: [PdCl(C3H5)]2 (0.01 mmol), heteroaryl bromide (1 mmol), 1-(toluene-4-
sulfonyl)pyrrole (1.5 mmol), KOAc (3 mmol), DMAc (5 mL), 20 h, 130 °C, isolated
yields.
a
4-Iodotoluene instead of 4-bromotoluene.

512
C. B. Bheeter et al. / Tetrahedron Letters 53 (2012) 509–513
1979–1982; (b) Liégaut, B.; Lapointe, D.; Caron, L.; Vlassova, A.; Fagnou, K. J.
NaOH, MeOH
70 °C, 2 h
Org. Chem. 2009, 74, 1826–1834; (c) Roger, J.; Doucet, H. Adv. Synth. Catal. 2009,
351, 1977–1990; (d) Fall, Y.; Doucet, H.; Santelli, M. ChemSusChem 2009, 2,
153–157; (e) Gryko, D. T.; Vakuliuk, O.; Gryko, D.; Koszarna, B. J. Org. Chem.
2009, 74, 9517–9520; (f) Liegault, B.; Petrov, I.; Gorelsky, S. I.; Fagnou, K. J. Org.
Chem. 2010, 75, 1047–1060; (g) Rene, O.; Fagnou, K. Adv. Synth. Catal. 2010, 352,
2116–2120; (h) Nadres, E. T.; Lazareva, A.; Daugulis, O. J. Org. Chem. 2011, 76,
471–483; (i) Vakuliuk, O.; Koszarna, B.; Gryko, D. T. Adv. Synth. Catal. 2011, 353,
925–930.
N
N
N
N
H
Ts
17
20 89%
Scheme 6. Deprotection of 17.
6. For selected examples of direct arylations of NH-free indoles: (a) Bellina, F.;
Cauteruccio, S.; Rossi, R. Eur. J. Org. Chem. 2006, 1379–1382; (b) Bellina, F.;
Calandri, C.; Cauteruccio, S.; Rossi, R. Tetrahedron 2007, 63, 1970–1980; (c)
Joucla, L.; Batail, N.; Djakovitch, L. Adv. Synth. Catal. 2010, 352, 2929–2936.
7. For examples of direct arylations of pyrrolyl salts: (a) Filippini, L.; Gusmeroli,
M.; Riva, P. Tetrahedron Lett. 1992, 33, 1755–1758; (b) Rieth, R. D.; Mankad, N.
P.; Calimano, E.; Sadighi, J. P. Org. Lett. 2004, 6, 3981–3983; (c) Swartz, D. L.;
Odom, A. L. Organometallics 2006, 25, 6125–6133.
8. For examples of palladium-catalysed direct arylations of NH-free pyrroles: (a)
Aoyagi, Y.; Inoue, A.; Koizumi, I.; Hashimoto, R.; Tokunaga, K.; Gohma, K.;
Komatsu, J.; Sekine, K.; Miyafuji, A.; Kunoh, J.; Honma, R.; Akita, Y.; Ohta, A.
Heterocycles 1992, 33, 257–272; (b) Romero, M.; Harrak, Y.; Basset, J.; Ginet, L.;
Constans, P.; Pujol, M. D. Tetrahedron 2006, 62, 9010–9016; (c) Wang, X.;
Gribkov, D. V.; Sames, D. J. Org. Chem. 2007, 72, 1476–1479; (d) Jafarpour, F.;
Rahiminejadan, S.; Hazrati, H. J. Org. Chem. 2010, 75, 3109–3112.
9. For an example of rhodium-catalysed direct arylations of a NH-free pyrrole:
Wang, X.; Lane, B. S.; Sames, D. J. Am. Chem. Soc. 2005, 127, 4996–4997.
10. For examples of iridium-catalysed direct arylations of N-tosylpyrrole: Join, B.;
Yamamoto, T.; Itami, K. Angew. Chem., Int. Ed. 2009, 48, 3644–3647.
11. For examples of palladium-catalysed intramolecular direct arylations of N-
tosylpyrroles: (a) Joucla, L.; Popowycz, F.; Lozach, O.; Meijer, L.; Joseph, B. Helv.
Chim. Acta 2007, 90, 753–763; (b) Kowada, T.; Yamaguchi, S.; Fujinaga, H.; Ohe,
K.-I. Tetrahedron 2011, 67, 3105–3110.
properties.13 However, 2-bromobenzonitrile gave 14 in 60% yield
(Table 1, entry 11).
Pyridines, quinolines or pyrimidines are among the most
common heterocyclic motifs found in pharmaceutically active
compounds. Therefore, preparative methods of biheteroaryl deriv-
atives containing such heterocycles remain an essential research
topic in organic synthesis. The reaction of 3-, 4-bromopyridines,
3-bromoquinoline, 4-bromoisoquinoline or 5-pyrimidine with
1-(toluene-4-sulfonyl)pyrrole gave the expected coupling products
15–19 in 40–58% yields (Table 3).
It should be noted that the deprotection of 17 was found to pro-
ceed nicely in methanol using 2 equiv of NaOH as the base at 70 °C,
and the desired product 20 was obtained in 89% yield (Scheme 6).
In summary, we report here that a range of aryl bromides un-
dergo palladium-catalysed coupling via C–H bond activation/func-
tionalisation reaction with N-tosylpyrrole in moderate to good
yields using 1 mol % [PdCl(C3H5)]2 as the catalyst. Ohta and co-
workers observed the formation of a mixture of C2 and C3 arylated
products for this reaction.8a However, with our reaction conditions,
the arylations were found to be highly regioselective in favour of
carbon C2. The yields obtained using N-tosylpyrrole were found
to be higher than with NH-free pyrrole. However, the reactivity
of these two pyrroles is much lower than N-alkyl pyrroles. As both
pyrrole and tosyl chloride are available on large scale at an
affordable price, and as the protection of pyrrole and deprotection
of N-tosylpyrrole are very easy, this reaction provides a convenient
access to NH-free 2-arylpyrroles. Moreover, it should be noted that
a wide variety of functional groups on the aryl bromide such as
formyl, propionyl, ester, nitrile, trifluoromethyl, chloro or fluoro
are tolerated.
12. For examples of deprotection of N-tosylpyrroles: (a) Merrill, B. A.; LeGoff, E. J.
Org. Chem. 1990, 55, 2904–2908; (b) Settambolo, R.; Lazzaroni, R.; Messeri, T.;
Mazzetti, M.; Salvadori, P. J. Org. Chem. 1993, 58, 7899–7902.
13. (a) Feuerstein, M.; Doucet, H.; Santelli, M. Synlett 2001, 1980–1982; (b)
Feuerstein, M.; Berthiol, F.; Doucet, H.; Santelli, M. Synthesis 2004, 1281–1289.
14. General procedure for coupling reactions: In
a typical experiment, aryl
bromide (1 mmol), heteroaromatic derivative (1.5 mmol), KOAc (0.294 g,
3 mmol) and [PdCl(C3H5)]2 (0.036 g, 0.01 mmol) were dissolved in DMAc
(5 mL) in a Schlenk tube under an argon atmosphere. The reaction mixture was
stirred at 130 °C for 20 h. The solvent was removed in vacuo, then the crude
mixture was purified by silica gel column chromatography.
15. All compounds gave satisfactory 1H, 13C and elementary analysis. 1H NMR
(300 MHz, DMSO-d6) and 13C NMR (75 MHz, DMSO-d6) of new compounds:
Compound 1: 1H NMR d 11.57 (s, 1H), 7.78 (s, 4H), 6.98 (m, 1H), 6.75 (m, 1H),
6.19 (m, 1H). 13C NMR d 137.8, 133.2, 129.9, 123.9, 122.1, 119.8, 110.4, 109.2,
107.3. Compound 2: 1H NMR d 7.84 (d, J = 8.0 Hz, 2H), 7.58 (dd, J = 3.1, 1.8 Hz,
1H), 7.44 (d, J = 8.0 Hz, 2H), 7.32 (s, 4H), 6.50–6.42 (m, 2H), 2.33 (s, 3H). 13C
NMR d 145.5, 135.8, 124.5, 134.1, 131.4, 130.7, 130.0, 126.4, 126.2, 118.7,
118.2, 113.7, 110.6, 21.0. Compound 5: 1H NMR d 10.06 (s, 1H), 7.90 (d,
J = 8.0 Hz, 2H), 7.57 (dd, J = 3.1, 1.8 Hz, 1H), 7.48 (d, J = 8.0 Hz, 2H), 7.32 (s, 4H),
6.50–6.42 (m, 2H), 2.33 (s, 3H). 13C NMR d 192.7, 145.4, 136.9, 135.4, 134.8,
134.7, 130.6, 130.0, 128.6, 126.5, 126.0, 117.9, 113.7, 21.0. Compound 6: 1H
NMR d 7.94 (d, J = 8.0 Hz, 2H), 7.55 (dd, J = 3.1, 1.8 Hz, 1H), 7.38 (d, J = 8.0 Hz,
2H), 7.32 (s, 4H), 6.45 (t, J = 3.1 Hz, 1H), 6.41–6.37 (m, 1H), 3.08 (q, J = 7.5 Hz,
2H), 2.34 (s, 3H), 1.11 (t, J = 7.5 Hz, 3H). 13C NMR d 200.0, 145.3, 135.8, 135.5,
134.9, 134.7, 130.2, 129.9, 127.0, 126.5, 125.7, 117.6, 113.6, 31.3, 21.0, 8.1.
Compound 7: 1H NMR d 7.94 (d, J = 8.0 Hz, 2H), 7.56 (dd, J = 3.1, 1.8 Hz, 1H),
7.37 (d, J = 8.0 Hz, 2H), 7.32 (s, 4H), 6.45 (t, J = 3.1 Hz, 1H), 6.40 (dd, J = 3.3,
1.8 Hz, 1H), 3.88 (s, 3H), 2.34 (s, 3H). 13C NMR d 165.9, 145.3, 135.8, 134.7,
134.6, 130.3, 129.9, 129.0, 128.3, 126.4, 125.8, 117.6, 113.5, 52.2, 21.0.
Compound 8: 1H NMR d 7.73 (d, J = 8.0 Hz, 2H), 7.56 (dd, J = 3.1, 1.8 Hz, 1H),
7.46 (d, J = 8.0 Hz, 2H), 7.32 (s, 4H), 6.46 (t, J = 3.1 Hz, 1H), 6.42 (dd, J = 3.3,
1.8 Hz, 1H), 2.34 (s, 3H). 13C NMR d 145.4, 135.2, 134.6, 134.2, 130.7, 129.9,
128.3 (q, J = 31.8 Hz), 126.5, 125.7, 124.3 (q, J = 3.8 Hz), 124.1 (q, J = 272.1 Hz),
117.7, 113.5, 21.0. Compound 9: 1H NMR d 7.50 (dd, J = 3.1, 1.8 Hz, 1H), 7.35–
7.15 (m, 8H), 6.41 (t, J = 3.1 Hz, 1H), 6.27 (dd, J = 3.3, 1.8 Hz, 1H), 2.34 (s, 3H).
13C NMR d 162.0 (d, J = 245.7 Hz), 145.2, 134.8, 134.4, 132.4 (d, J = 8.5 Hz),
129.9, 127.3 (m), 126.5, 124.5, 116.4, 114.4 (d, J = 21.6 Hz), 112.8, 21.0.
Compound 11: 1H NMR d 7.46 (dd, J = 3.1, 1.8 Hz, 1H), 7.35 (d, J = 8.0 Hz, 2H),
7.26 (s, 4H), 7.12 (d, J = 8.0 Hz, 2H), 6.39 (t, J = 3.1 Hz, 1H), 6.23 (dd, J = 3.3,
1.8 Hz, 1H), 2.34 (s, 3H), 1.31 (s, 9H). 13C NMR d 150.7, 145.0, 135.6, 134.9,
130.0, 129.7, 128.2, 126.6, 124.2, 124.1, 115.9, 112.7, 34.3, 31.1, 21.0.
Compound 12: 1H NMR d 7.44 (dd, J = 3.1, 1.8 Hz, 1H), 7.24 (d, J = 8.0 Hz, 2H),
7.18 (d, J = 8.0 Hz, 2H), 7.12 (d, J = 8.0 Hz, 2H), 7.05 (d, J = 8.0 Hz, 2H), 6.33 (t,
J = 3.1 Hz, 1H), 6.13 (dd, J = 3.3, 1.8 Hz, 1H), 2.38 (s, 3H), 2.36 (s, 3H). 13C NMR d
145.0, 137.9, 136.2, 135.6, 130.5, 129.1, 128.6, 127.6, 126.8, 123.7, 115.2, 111.7,
20.1, 19.9. Compound 13: 1H NMR d 7.90–7.80 (m, 1H), 7.60–7.52 (m, 4H), 7.32
(d, J = 8.0 Hz, 2H), 7.28 (d, J = 8.0 Hz, 2H), 6.45 (t, J = 3.1 Hz, 1H), 6.42 (dd,
J = 3.3, 1.8 Hz, 1H), 2.35 (s, 3H). 13C NMR d 145.5, 134.9, 134.7, 133.4, 133.3,
132.2, 131.8, 130.0, 128.8, 126.5, 125.4, 118.4, 117.6, 113.3, 110.8, 21.0.
Compound 14: 1H NMR d 7.86 (d, J = 7.8 Hz, 1H), 7.71 (t, J = 7.8 Hz, 1H), 7.63 (d,
J = 7.8 Hz, 1H), 7.60 (dd, J = 3.1, 1.8 Hz, 1H), 7.35–7.30 (m, 5H), 6.49 (t,
J = 3.1 Hz, 1H), 6.47 (dd, J = 3.3, 1.8 Hz, 1H), 2.35 (s, 3H). 13C NMR d 145.4,
134.7, 134.3, 132.4, 132.2, 132.1, 130.6, 130.0, 129.4, 126.5, 125.0, 118.0, 117.4,
Acknowledgments
This research was supported by a CEFIPRA fellowship. We thank
the CNRS and ‘Rennes Metropole’ for providing financial support.
References and notes
1. (a) Jones, R. A. Pyrroles; Wiley-Interscience: New York, 1990; (b) Li, J. J.; Gribble,
G. W. Palladium in Heterocyclic Chemistry; Pergamon: Amsterdam, 2000.
2. Ohta, A.; Akita, Y.; Ohkuwa, T.; Chiba, M.; Fukunaga, R.; Miyafuji, A.; Nakata, T.;
Tani, N.; Aoyagi, Y. Heterocycles 1990, 31, 1951–1958.
3. (a) Alberico, D.; Scott, M. E.; Lautens, M. Chem. Rev. 2007, 107, 174–238; (b)
Satoh, T.; Miura, M. Chem. Lett. 2007, 36, 200–205; (c) Campeau, L.-C.; Stuart, D.
R.; Fagnou, K. Aldrichimica Acta 2007, 40, 35–41; (d) Seregin, I. V.; Gevoryan, V.
Chem. Soc. Rev. 2007, 36, 1173–1193; (e) Li, B.-J.; Yang, S.-D.; Shi, Z.-J. Synlett
2008, 949–957; (f) Bellina, F.; Rossi, R. Tetrahedron 2009, 65, 10269–10310; (g)
Ackermann, L.; Vincente, R.; Kapdi, A. R. Angew. Chem., Int. Ed. 2009, 48, 9792–
9826; (h) Roger, J.; Gottumukkala, A. L.; Doucet, H. Chem. Cat. Chem. 2010, 2,
20–40; (i) Fischmeister, C.; Doucet, H. Green Chem. 2011, 13, 741–753.
4. For selected recent examples of direct arylations from our laboratory: (a)
Derridj, F.; Roger, J.; Geneste, F.; Djebbar, S.; Doucet, H. J. Organomet. Chem.
2009, 694, 455–465; (b) Roger, J.; Doucet, H. Tetrahedron 2009, 65, 9772–9781;
ˇ
(c) Dong, J. J.; Roger, J.; Pozgan, F.; Doucet, H. Green Chem. 2009, 11, 1832–1846;
(d) Dong, J. J.; Roger, J.; Doucet, H. Tetrahedron Lett. 2009, 50, 2778–2781; (e)
ˇ
Roger, J.; Pozgan, F.; Doucet, H. Green Chem. 2009, 11, 425–432; (f) Fall, Y.;
Reynaud, C.; Doucet, H.; Santelli, M. Eur. J. Org. Chem. 2009, 4041–4050; (g)
Roger, J.; Verrier, C.; Le Goff, R.; Hoarau, C.; Doucet, H. ChemSusChem 2009, 2,
951–956; (h) Ionita, M.; Roger, J.; Doucet, H. ChemSusChem 2010, 3, 367–376;
(i) Derridj, F.; Roger, J.; Djebbar, S.; Doucet, H. Org. Lett. 2010, 12, 4320–4323; (j)
Roger, J.; Pozgan, F.; Doucet, H. Adv. Synth. Catal. 2010, 352, 696–710.
5. For recent examples of intermolecular direct arylations of N-alkyl- or N-
arylpyrroles: (a) Toure, B. B.; Lane, B. S.; Sames, D. Org. Lett. 2006, 8,

C. B. Bheeter et al. / Tetrahedron Letters 53 (2012) 509–513
513
113.9, 113.1, 21.1. Compound 15: 1H NMR d 7.58 (dd, J = 4.7, 1.3 Hz, 1H), 8.34
(d, J = 1.7 Hz, 1H), 7.67 (dt, J = 8.0, 1.7 Hz, 1H), 7.57 (dd, J = 3.1, 1.8 Hz, 1H), 7.41
(dd, J = 8.0, 4.7 Hz, 1H), 7.33 (d, J = 8.0 Hz, 2H), 7.28 (d, J = 8.0 Hz, 2H), 6.46 (t,
J = 3.1 Hz, 1H), 6.41 (dd, J = 3.3, 1.8 Hz, 1H), 2.34 (s, 3H). 13C NMR d 150.0,
149.1, 145.4, 137.7, 134.7, 132.0, 130.0, 127.2, 126.4, 125.3, 122.6, 117.5, 113.3,
21.0. Compound 16: 1H NMR d 8.57 (d, J = 5.8 Hz, 2H), 7.59 (dd, J = 3.1, 1.8 Hz,
1H), 7.37 (d, J = 8.0 Hz, 2H), 7.29 (d, J = 8.0 Hz, 2H), 7.27 (d, J = 5.8 Hz, 2H), 6.50
(dd, J = 3.3, 1.8 Hz, 1H), 6.47 (t, J = 3.1 Hz, 1H), 2.34 (s, 3H). 13C NMR d 148.9,
145.5, 138.6, 134.5, 133.2, 130.0, 126.5, 126.4, 124.3, 118.5, 113.8, 21.0.
Compound 17: 1H NMR d 8.66 (d, J = 2.0 Hz, 1H), 8.09 (d, J = 2.0 Hz, 1H), 8.05 (d,
J = 8.4 Hz, 1H), 7.88 (d, J = 8.4 Hz, 1H), 7.80 (t, J = 8.0 Hz, 1H), 7.61 (t, J = 8.4 Hz,
1H), 7.58 (dd, J = 3.1, 1.8 Hz, 1H), 7.18 (d, J = 8.4 Hz, 2H), 7.11 (d, J = 8.4 Hz, 2H),
6.45 (t, J = 3.1 Hz, 1H), 6.41 (dd, J = 3.3, 1.8 Hz, 1H), 2.31 (s, 3H). 13C NMR
(MeOD) d 149.7, 144.8, 144.0, 136.2, 133.9, 130.4, 128.8, 127.9, 126.6, 126.1,
125.7, 125.0, 123.7, 123.6, 116.0, 111.0, 18.6. Compound 18: 1H NMR d 8.75 (d,
J = 1.8 Hz, 1H), 8.18 (d, J = 1.8 Hz, 1H), 8.07 (d, J = 8.4 Hz, 1H), 7.99 (d, J = 8.4 Hz,
1H), 7.82 (t, J = 8.0 Hz, 1H), 7.66 (t, J = 8.4 Hz, 1H), 7.62 (dd, J = 3.1, 1.8 Hz, 1H),
7.29 (s, 4H), 6.52 (dd, J = 3.3, 1.8 Hz, 1H), 6.50 (t, J = 3.1 Hz, 1H), 2.32 (s, 3H). 13
C
NMR d 151.2, 146.6, 145.4, 136.3, 134.8, 132.2, 130.1, 130.0, 128.6, 128.3,
127.1, 126.6, 126.4, 125.5, 124.6, 118.1, 113.6, 21.0. Compound 19: 1H NMR d
9.19 (s, 1H), 8.67 (s, 2H), 7.64 (dd, J = 3.1, 1.8 Hz, 1H), 7.33 (s, 4H), 6.57 (dd,
J = 3.3, 1.8 Hz, 1H), 6.52 (t, J = 3.1 Hz, 1H), 2.35 (s, 3H). 13C NMR d 157.6, 156.9,
145.7, 134.6, 130.2, 128.4, 126.3, 126.1, 125.7, 118.7, 113.7, 21.0. Deprotection
of 17 into 20: 1H NMR (MeOD) d 9.10 (d, J = 2.0 Hz, 1H), 8.31 (d, J = 2.0 Hz, 1H),
7.94 (d, J = 8.4 Hz, 1H), 7.84 (d, J = 8.4 Hz, 1H), 7.63 (t, J = 8.0 Hz, 1H), 7.53 (t,
J = 8.4 Hz, 1H), 6.95 (m, 1H), 6.73 (m, 1H), 6.26 (dd, J = 3.5, 2.4 Hz, 1H). 13C NMR
(MeOD) d 147.2, 145.2, 128.9, 128.4, 128.1, 127.9, 127.5, 127.4, 127.0, 126.9,
120.4, 109.4, 107.0.