Palladium-Polypyrrole Nanocomposites Pd@PPy for Direct C-H Functionalization of Pyrroles and Imidazoles with Bromoarenes

Article abstract of DOI:10.1055/s-0035-1561113

Palladium-polypyrrole nanocomposites (Pd@PPy) with unique combination of high palladium dispersion (nanoparticle size 2.4 nm) and high palladium content (35 wt%) are efficient catalysts for the selective arylation of substituted pyrroles and imidazoles with either activated or deactivated aryl bromides. The performances of the recoverable supported palladium catalyst matches the best performances of homogeneous systems based on Pd(OAc)₂ at 0.5-0.2 mol%, and largely overwhelm the classical Pd/C catalyst.

Full text of DOI:10.1055/s-0035-1561113

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Palladium–Polypyrrole Nanocomposites Pd@PPy for Direct C–H
Functionalization of Pyrroles and Imidazoles with Bromoarenes
Pierre Bizouarda
Christelle Testaa
Direct C–H arylation of N-methyl pyrroles and imidazoles: 14–99%
Pd(0)
Veronika A. Zinovyeva*b
Julien Roger*a
N
R2
N
n
H
R4 R4 = H, (4-COMe)C6H4,
(4-CN)C6H4, (4-OMe)C6H4
Jean-Cyrille Hierso*a,c
R1
R3
N
N
Pd@PPy
R1 = CHO, COMe
2 = 4-CN, 4-OMe, 4-Me,
2-F, 2-Me, 2-CN, 3-Me, etc.
a Institut de Chimie Moléculaire de l’Université de Bourgogne,
ICMUB-UMR CNRS 6302, Université de Bourgogne Franche-
Comté, 9 Avenue Alain Savary, 21078 Dijon Cedex, France
julien.roger@u-bourgogne.fr
R
3 = H, (4-COMe)C6H4
R
jean-cyrille.hierso@u-bourgogne.fr
b Institut de Physique Nucléaire, CNRS-IN2P3, Univ. Paris-Sud,
Université Paris-Saclay, 91406 Orsay Cedex, France
veronika.zinovyeva@u-psud.fr
c Institut Universitaire de France (IUF), 103 Boulevard Saint
Michel, 75005 Paris Cedex, France
Dedicated to the memory of Dr. Guy Lavigne
Received: 10.11.2015
Accepted after revision: 14.12.2015
Published online: 05.01.2016
cient heterogeneous catalytic systems have been reported,
which are mainly based on [Pd/C] and [Pd(OH)2/C].3 Match-
ing the catalytic performances which are obtained under
homogeneous conditions with supported catalysts is diffi-
cult to achieve from metal deposition on elusive carbon ma-
terials. Our group is thus looking for easily recoverable and
potentially recyclable palladium composites ‘NP@support’,
with the need of an accurate and reproducible control of
the heterogeneous catalytic materials formation.
Vasilyeva and Vorotyntsev have reported on the produc-
tion and characterization of an innovative composite mate-
rial under the form of palladium supported on polypyrrole
(Pd@PPy) obtained from a mixture of Pd(OAc)2 and pyr-
role.4 The composite formation occurred via reduction of
Pd2+ cations by oxidized pyrrole monomer in acetonitrile
solvent. The synthetic protocol led to palladium nanoclus-
ters of 2.0–2.5 nm diameters dispersed within spherical
PPy of a few hundred nanometers. Improvements by Zi-
novyeva and Vorotyntsev have led to the formation of
Pd@PPy hybrid catalytic materials in water via redox po-
lymerization reaction of pyrrole with [Pd(NH3)4Cl2]
(Scheme 1).5 The nanocomposites formed were composed
of highly dispersed zero-valent palladium nanoparticles
embedded in spherical polypyrrole globules. A unique com-
bination of high palladium dispersion (NP size: 2.4 nm) and
high palladium content (35 wt%) has been obtained. These
versatile synthesis can give access to supported palladium
with sizes ranging between 1.0–2.0 nm that have been test-
ed for Suzuki–Miyaura coupling,6a phenylacetylene Sono-
gashira arylation,6b and aryl halide cyanation.6c
DOI: 10.1055/s-0035-1561113; Art ID: st-2015-u0883-c
Abstract Palladium–polypyrrole nanocomposites (Pd@PPy) with
unique combination of high palladium dispersion (nanoparticle size 2.4
nm) and high palladium content (35 wt%) are efficient catalysts for the
selective arylation of substituted pyrroles and imidazoles with either ac-
tivated or deactivated aryl bromides. The performances of the recover-
able supported palladium catalyst matches the best performances of
homogeneous systems based on Pd(OAc)2 at 0.5–0.2 mol%, and largely
overwhelm the classical Pd/C catalyst.
Key words palladium, polypyrrole, nanocomposite, C–H arylation,
azoles
Palladium-catalyzed sp2C–sp2C bond formations are
powerful modern synthetic methodologies, which include
reactions between organometallic reagents and organic
electrophiles. While very efficient, these reactions, which
are based on organometallic reagents (for instance organo-
boron, organotin, organomagnesium, organozinc, or orga-
nosilane reagents), generate stoichiometric metallic waste
and require prefunctionalization of aromatic substrates.
Therefore, the research focus has shifted in the last decade
to direct C–H functionalization of aromatic and heteroaro-
matic substrates.1 Homogeneous conditions for these direct
arylation reactions are well-established,2 and the use of
heterogeneous catalysts and stable nanoparticles (NP) is
now a very appealing step forward for industrial applica-
tion. The inertness of the C–H bond has rendered such aus-
picious advances rather difficult, and to date only few effi-
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Screening of appropriate conditions for coupling N-
Pd(0)
H2O (0.5 L), 50 °C
N
[PdII(NH3)4Cl2]
(2.5 mmol)
methylpyrrole-2-carboxaldehyde (1a) to 4-bromoacetophe-
none (2a, Scheme 2) is reported in Table 1. We identified
two main side reactions which are deleterious for the selec-
tivity of C–H arylation: the dehalogenation of 2a to 4, and
its homocoupling to form 5. Using two equivalents of pyr-
role substrate was a practical way to diminish or obliterate
these side reactions.
= Pd@PPy
+
N
H
n
ultrasonic bath
(25 h over 5 d)
H
(150 mmol)
Scheme 1 In-water mild redox polymerization reaction of pyrrole with
[Pd(NH3)4Cl2] to Pd@PPy nanocomposite
Our group has developed application of these novel hy-
brid nanomaterials in the palladium-catalyzed direct aryla-
tion of heteroaromatics.5 High efficiency and perfect selec-
tivity in C–C bond formation has been obtained for furans
and thiophenes C5-arylation by using bromoarenes.
Pd@PPy nanocomposites can efficiently couple n-butyl fu-
ran and n-butyl thiophene with bromobenzene and bromo-
quinoline, as well as with activated or deactivated electron-
poor and electron-rich functionalized bromoarenes. As un-
derlined by Felpin and Fairlamb,3,7 this Pd@PPy nanocom-
posite is a rare example of palladium NP supported on or-
ganic material with a record high metal density.
We now report on the efficiency of these Pd@PPy nano-
composites for the selective arylation of more demanding
azole substrates: pyrroles and imidazoles. We anticipated
two main difficulties for an effective C–H arylation: the
general lower acidity of C5–H (or C2–H) adjacent to nitro-
gen in pyrroles and other azoles,8 and also the fact that het-
eroaromatic substrates and the polymeric organic support
were of a similar nature, with a much higher acidity for
N–H in pyrrole (pKa = 23.0).
The important role of solvent and temperature was first
evidenced since activation temperatures around 150 °C in a
polar solvent were necessary for achieving any conversion
of 1a [Table 1, entries 1–3 using toluene, cyclopentyl meth-
yl ether (CPME), and dimethylformamide (DMF)]. We were
glad to see that dimethylacetamide (DMAc) was very effi-
cient for a full conversion of 1a selectively into 3a (Table 1,
entry 4) despite the foreseen troubles above mentioned.
These conditions (DMAc, 150 °C, 17 h, KOAc) were then se-
lected to pursue our screening since we noted that chang-
ing KOAc base for K2CO3 was deleterious for conversion and
promoted homocoupling of 2a to 5 (Table 1, entry 5). For
comparison we also investigated the efficiency of related
catalytic systems. The use of palladium on activated char-
coal (Pd/C 10 wt%, Aldrich, CAS: 7440-05-03) led to dehalo-
genation of 2a (Table 1, entry 6), and evidenced in contrast
the excellent conversion and high selectivity of Pd@PPy.
The use of soluble Pd(OAc)2 was found fairly efficient for
loading ranging between 0.5 and 0.2% (Table 1, entries 8
and 9). Lower loading Pd(OAc)2 at 0.02% (Table 1, entry 10),
COMe
4
[Pd]
+
H
Br
COMe
COMe
+
N
OHC
N
OHC
base (2.0 equiv)
MeOC
COMe
1a
(2.0 equiv)
solvent, T °C, 17 h
2a
3a
(1.0 equiv)
5
Scheme 2 Palladium arylation of N-methyl-pyrrole-2-carboxaldehyde 1a with 4-bromoacetophenone 2a
Table 1 Screening Conditions to Arylated Pyrrole 3a with Pd@PPy and Comparison with Other Pertinent Palladium-Based Catalystsa
Entry
Catalyst (%)
Solvent
Temp (°C)
Base
KOAc
Conv. (%)
Yield of 3 (%)
Yield of 4 (%) Yield of 5 (%)
1
2
Pd@PPy (2)
Pd@PPy (2)
Pd@PPy (2)
Pd@PPy (2)
Pd@PPy (2)
Pd/C (2)
toluene
CPME
DMF
110
125
150
150
150
150
150
150
150
150
0
0
–
–
–
–
–
KOAc
KOAc
KOAc
K2CO3
KOAc
KOAc
KOAc
KOAc
KOAc
–
3
99
99
99b
99
99
99
99
87
92
99
0
0
2
4
DMAc
DMAc
DMAc
DMAc
DMAc
DMAc
DMAc
0
0
5
0
60
5
6
79
80
88
92
81
16
0
7
Pd(OAc)2 (2)
Pd(OAc)2 (0.5)
Pd(OAc)2 (0.2)
Pd(OAc)2 (0.02)
20
12
2
8
0
9
5
10
1
4
a 1H NMR yields (consistent with GC) from at least 2 runs.
b Unidentified products are formed.
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or higher loading Pd(OAc)2 at 2% (Table 1, entry 7), were
found detrimental to full conversion of 1a and also favored
homocoupling.
CN
N
OHC
COMe
OHC
N
N
OHC
COMe
N
With optimized conditions in hands using the recover-
able catalytic material Pd@PPy (Table 1, entry 4) we exam-
ined the scope of C–H functionalization of pyrroles. We in-
vestigated in parallel the activity achieved under the best
homogeneous conditions using Pd(OAc)2 (Table 1, entries 8
and 9). Roger and Doucet first reported on the efficiency for
pyrroles C–H arylation of the Pd(OAc)2 precatalyst used at
low loading.9 In our case, the coupling of para-substituted
bromoarenes with N-methylpyrrole-2-carboxaldehyde 1a
using Pd@PPy was efficiently achieved under the optimized
conditions (Figure 1, conditions A). Compound 3a was iso-
lated in 58% yield from full conversion of ArBr 2a;10 then re-
cycling of Pd@PPy was achieved with the synthesis of 3a in
93%. The arylation is tolerant to various electron-withdraw-
ing or electron-donating functional groups on aryl bromide,
including cyano (3b, 76%), trifluoromethyl (3c, 75%), me-
thoxy (3d, 92%), and methyl (3e, 90%). The performances of
Pd@PPy for 1a arylation mostly compared well, and even
sometimes outclassed (for instance with electron-rich 3d)
our results under optimized homogeneous conditions using
Pd(OAc)2 at 0.2 mol%. This tendency was confirmed with
the coupling of N-methyl-2-acetylpyrrole 1b to form 6a in
89% with Pd@PPy and only 70% with the homogeneous sys-
tem.
A: 99% (58)a
B: 92%
D: 88%
C: 93%
A: 76% (41)
B: 77%
3a
3a
3b
Me
N
OHC
OMe
CF3
OHC
N
OHC
3c
A: 75% (42)
B: 72%
3d
A: 92% (35)
B: 46%
3e
A: 90% (68)
B: 93%
F
NC
COMe
N
N
N
MeOC
6a
OHC
OHC
7a
7b
A: 89% (28)
B: 70%
A: 79% (57)
B: 91%
D: 84%
A: 75% (26)
B: 74%
D: 85%
Me
Me
MeOC
N
OHC
N
N
OHC
7c
MeOC
A: 85% (35)
B: 79%
D: 81%
7d
A: 83% (41)
B: 89%
D: 76%
8a
A: 14%
B: 32%
D: 17%
Me
N
MeOC
8b
A: 74% (23)
B: 85%
D: 78%
The scope was extended to ortho-substituted bromides,
and good conversions were obtained for coupling pyrroles
1a and 1b to aryl bromides having ortho substituents with
electron-attracting (CN: 7a, 79%; F: 7b, 75%) and electron-
donating properties (Me: 7c, 85%; 8b, 74%). The formation
of 8a which bears a more bulky o-acetyl group was limited
to 15–30% for supported and homogeneous catalytic sys-
tems. This remarkable steric effect has not been reported
before and is supported by the fact that contrary to the case
of para-substituted bromoarenes the nonsupported cata-
lytic system appears significantly more efficient. Thus, yield
improvement (up to 15%) might be attributed to more ac-
cessible catalytic centers in the homogeneous system. The
coupling of a meta-substituted bromide was also achieved
with good yield and led to 7d in 83%. We investigated the
coupling of electron-poor 4-chlorobenzonitrile to 1a. Using
2.0 mol% of Pd@PPy less than 10% yield of 3a was obtained.
This result was improved up to about 30% by addition of ex-
cess of tert-butyl ammonium salt TBAB.
Figure 1 C5-Arylated pyrroles 3a–e, 6a, 7a–d, and 8a,b synthesized
from bromoarenes. Reagents and conditions: pyrrole (2 equiv), bro-
moarene (1 equiv), DMAc (2.5 ml), KOAc (2 equiv), 150 °C, 17 h; condi-
tions A: Pd@PPy (2.0 mol%); conditions B: Pd(OAc)2 0.2 mol%;
conditions C: recycling of conditions A; conditions D: Pd(OAc)2 (0.5
mol%). a NMR and GC yields (consistent); isolated yields are in brackets,
values are diminished due to reactions being carried out on very low
scale (1.0 mmol).
N-methylimidazole to bromoarenes (Scheme 3). In this
type of coupling the competition between C5–H and C2–H
functionalization may occur, leading to mono- and diarylat-
ed compounds.11
Conditions for selective coupling have been reported in
which the control of selectivity is exerted by the base set-
tings.9,12 We examined the performances of the nanocom-
posite Pd@PPy for the arylation of N-methylimidazole 9
with aryl bromides (Figure 2). By using two equivalents of
KOAc (previously optimized conditions A), selective C5-ary-
lation led to 10a (62%), 11a (92%), and 12a (76%) in good to
high yields. These products are para-substituted either
with electron-poor or electron-rich functions. By using two
Encouraged by the good performances associated to
bromoarenes coupling, we then investigated the coupling of
N
N
N
N
[Pd]
Ar
+
H
+ homocoupling
+ debromination
Ar
+
+
H
C5
Br
R
N
N
Ar
N
H
Ar
N
H
C2
base
Scheme 3 Palladium arylation of N-methylimidazole and expected products
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P. Bizouard et al.
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equivalents of Cs2CO3 as a base, with 1.0 equivalents of CuI,
arylation at C2 of N-methylimidazole was favored, and the
use of bromoarene 2a selectively led to 10b in 77% yield.
Again, for imidazoles the supported system compared well
with the best homogeneous palladium catalyst. We previ-
ously reported postcatalysis studies for this Pd@PPy sys-
tem, which suggested releasing of molecular or colloidal
soluble active species, delivered by the nanocomposite and
susceptible to back redeposition and recycling.5 To further
scrutinize this hypothesis we achieved here inductively
coupled plasma atomic emission spectroscopy (ICP-AES)
analysis of the filtrate after synthesis of 3a (Scheme 2). A
residual amount of palladium of 260 ppm which corre-
sponds to 2.7% palladium leaching was detected. In com-
parison to fully insoluble heterogeneous systems (<10
ppm),13 this amount is consistent with our first hypothesis.
References and Notes
(1) (a) Ritleng, V.; Sirlin, C.; Pfeffer, M. Chem. Rev. 2002, 102, 1731.
(b) Parisien, M.; Valette, D.; Fagnou, K. J. Org. Chem. 2005, 70,
7578. (c) Alberico, D.; Scott, M. E.; Lautens, M. Chem. Rev. 2007,
107, 174. (d) Satoh, T.; Miura, M. Chem. Lett. 2007, 36, 200.
(e) Kakiuchi, F. Synthesis 2008, 3013. (f) Bellina, F.; Rossi, R. Tet-
rahedron 2009, 65, 10269. (g) Ackermann, L.; Vicente, R.; Kapdi,
A. R. Angew. Chem. Int. Ed. 2009, 48, 9792. (h) Chen, X.; Engle, K.
M.; Wang, D.-H.; Yu, J.-Q. Angew. Chem. Int. Ed. 2009, 48, 5094.
(i) Roger, J.; Gottumukkala, A. L.; Doucet, H. ChemCatChem 2010,
2, 20. (j) Yamaguchi, J.; Yamaguchi, A. D.; Itami, K. Angew. Chem.
Int. Ed. 2012, 51, 8960. (k) Wencel-Delord, J.; Glorius, F. Nat.
Chem. 2013, 5, 369. (l) Rossi, R.; Bellina, F.; Lessi, M.; Manzini, C.
Adv. Synth. Catal. 2014, 356, 17.
(2) (a) Battace, A.; Lemhadri, M.; Zair, T.; Doucet, H.; Santelli, M.
Organometallics 2007, 26, 472. (b) Fall, Y.; Doucet, H.; Santelli,
M. ChemSusChem 2009, 2, 153. (c) Roy, D.; Mom, S.; Beaupérin,
M.; Doucet, H.; Hierso, J.-C. Angew. Chem. Int. Ed. 2010, 49, 6650.
(d) Roy, D.; Mom, S.; Lucas, D.; Cattey, H.; Hierso, J.-C.; Doucet,
H. Chem. Eur. J. 2011, 17, 6453. For selected examples of Pd-cat-
alyzed pyrrole and imidazole arylations on C2 or C5 with
haloarenes, see: (e) Pivas-Art, S.; Satoh, T.; Kawamura, Y.;
Miura, M.; Nomura, M. Bull. Chem. Soc. Jpn. 1998, 71, 467.
(f) Bellina, F.; Rossi, R. Tetrahedron 2006, 62, 7213. (g) Bellina, F.;
Calandri, C.; Cauteruccio, S.; Rossi, R. Tetrahedron 2007, 63,
1970. (h) Storr, T. E.; Firth, A. G.; Wilson, K.; Darley, K.;
Baumann, C. G.; Fairlamb, I. J. S. Tetrahedron 2008, 64, 6125.
(i) Jafarpour, F.; Rahiminejadan, S.; Hazrati, H. J. Org. Chem.
2010, 75, 3109. (j) Shibahara, F.; Yamaguchi, E.; Murai, T. Chem.
Commun. 2010, 46, 2471. (k) Zhao, L.; Bruneau, C.; Doucet, H.
ChemCatChem 2013, 5, 255. (l) Bellina, F.; Guazzelli, N.; Lessi,
M.; Manzini, C. Tetrahedron 2015, 71, 2298.
(3) Djakovitch, L.; Felpin, F.-X. ChemCatChem 2014, 6, 2175.
(4) Vasilyeva, S. V.; Vorotyntsev, M. A.; Bezverkhyy, I.; Lesniewska,
E.; Heintz, O.; Chassagnon, R. J. Phys. Chem. C 2008, 112, 19878.
(5) Zinovyeva, V. A.; Vorotyntsev, M. A.; Bezverkhyy, I.; Chaumont,
D.; Hierso, J.-C. Adv. Funct. Mater. 2011, 21, 1064.
(6) (a) Magdesieva, T. V.; Nikitin, O. M.; Levitsky, O. A.; Zinovyeva,
V. A.; Bezverkhyy, I.; Zolotukhina, E. V.; Vorotyntsev, M. A. J.
Mol. Catal. A: Chem. 2012, 50, 353. (b) Magdesieva, T. V.; Nikitin,
O. M.; Zolotukhina, E. V.; Zinovyeva, V. A.; Vorotyntsev, M. A.
Mendeleev Commun. 2012, 22, 305. (c) Magdesieva, T. V.;
Nikitin, O. M.; Zolotukhina, E. V.; Vorotyntsev, M. A. Electro-
chim. Acta 2014, 122, 289.
(7) Reay, A. J.; Fairlamb, I. J. S. Chem. Commun. 2015, 51, 16289.
(8) Reported pKa for thiophenes and furans are C5 (or C2)–H = 33–
36, and pKa of C5 (or C2)–H for pyrroles and indoles are in the
range 38–40, see http://www.scripps.edu/baran/heterocy-
cles/Essentials1-2009.pdf.
(9) Roger, J.; Doucet, H. Adv. Synth. Catal. 2009, 351, 1977.
(10) Improved isolated yields can be accessed for synthetic scales
higher than 1.0 mmol. Recycling experiments were limited due
to fractional material loss by paper filtration.
N
N
H
COMe
N
N
H
A: 62%a
D: 67%
E: 77%
D: 77%
MeOC
10b
10a
N
N
OMe
Me
N
N
H
H
A: 92%
D: 93%
A: 76%
D: 90%
11a
12a
Figure 2 C5- and C2-arylated imidazoles 10a,b, 11a, and 12a from
bromoarenes coupled with 9. Reagents and conditions: imidazole (2.0
equiv), bromoarene (1.0 equiv), DMAc (2.5 ml), 150 °C, 17 h; condi-
tions A: Pd@PPy (2.0 mol%), KOAc (2 equiv); conditions D: Pd(OAc)2
(0.5 mol%), KOAc (2.0 equiv); conditions E: Pd@PPy (2.0 mol%), CuI (1.0
equiv), Cs2CO3 (2.0 equiv). a NMR and GC yields.
In summary, palladium nanoparticles of 2 nm size,
highly dispersed on polypyrrole support (35 Pd wt%), pro-
vided an efficient system for the selective direct arylation
of substituted pyrroles and imidazoles by using unactivated
aryl bromides functionalized in para, meta, and ortho posi-
tions.14–16 These performances matches the best homoge-
neous systems known to date. Further works are focused at
improving the recyclability of this recoverable system via
anchoring of Pd@PPy nanocomposite.
Acknowledgment
This work was supported by the Université de Bourgogne (MESR PhD
grant for CT), the Région Bourgogne (PARI II program) and the CNRS
(3MIM-P4 program). We are thankful for support from the Institut
Universitaire de France IUF (JCH).
(11) Bellina, F.; Cauteruccio, S.; Di Fiore, A.; Marchetti, C.; Rossi, R.
Tetrahedron 2008, 64, 6060; see also ref. 2l.
(12) Smari, I.; Youssef, C.; Ben Ammar, H.; Ben Hassine, B.; Soulé, J.-
F.; Doucet, H. Tetrahedron 2015, 71, 6586.
Supporting Information
(13) (a) Beaupérin, M.; Smaliy, R.; Cattey, H.; Meunier, P.; Ou, J.; Toy,
P. H.; Hierso, J.-C. Chem. Commun. 2014, 50, 9505. (b) Beaupérin,
M.; Smaliy, R.; Cattey, H.; Meunier, P.; Ou, J.; Toy, P. H.; Hierso,
J.-C. ChemPlusChem 2015, 80, 119.
Supporting information for this article is available online at
http://dx.doi.org/10.1055/s-0035-1561113.
S
u
p
p
ortioInfgrmoaitn
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(14) Typical Procedure
(15) 1-[4-(5-Acetyl-1-methyl-1H-pyrrol-2-yl)phenyl]ethanone
(6a)
All reactions were run under argon in Schlenk tubes using
vacuum lines. DMAc analytical grade was not distilled before
use. KOAc (99%) was used. Commercial aryl bromides, pyrroles,
and imidazoles were used without purification. The reactions
were followed by GC and NMR spectroscopy. 1H NMR spectra
were recorded with a Bruker 300 MHz spectrometer in CDCl3
solutions. Chemical shifts are reported in ppm relative to CDCl3
(7.25 for 1H NMR). Flash chromatography was performed on
silica gel (230–400 mesh).
In a typical procedure, the aryl bromide (1 mmol), pyrrole (2
mmol), and KOAc (2 mmol) were introduced in a Schlenk tube,
equipped with a magnetic stirring bar. The catalyst [either
Pd@PPy,5 or Pd(OAc)2 at 0.02–2.0 mol%] and DMAc (2.5 ml)
were added, and the Schlenk tube was purged several times
using vacuum/argon flow. The Schlenk tube was placed in a pre-
heated oil bath at 150 °C, and reactants were allowed to stir for
17 h. The reaction mixture was analyzed by GC and NMR to
determine the conversion of aryl bromide. The solvent was then
removed by heating the reaction vessel under vacuum, and the
residue formed was charged directly onto a silica gel column.
The products were eluted, using an appropriate ratio of EtOAc
and heptane. Recycling procedure were based on simple
Pd@PPy powder paper filtration, rinsing with a small portion of
organic solvent, and drying under vacuum at 60 °C for 4 h. Sub-
sequent catalytic tests were conducted using DMAc at 150 °C in
the presence of KOAc and sufficient Pd@PPy collected from
several experiments.
The reaction of 4-bromoacetophenone (0.100 g, 1 mmol), 1-
methyl-2-acetylpyrrole (0.120 mL, 2 mmol), and KOAc (0.098 g,
2 mmol) with Pd@PPy (0.003 g, 2% mol) affords the correspond-
ing product 6a in 28% isolated yield. 1H NMR (200 MHz, CDCl3):
δ = 8.02 (d, J = 8.4 Hz, 2 H), 7.51 (d, J = 8.4 Hz, 2 H), 7.03 (d,
J = 4.0 Hz, 1 H), 6.29 (d, J = 4.0 Hz, 1 H), 3.91 (s, 3 H), 2.64 (s, 3
H), 2.48 (s, 3 H). 13C NMR (75 MHz, CDCl3): δ = 197.4, 188.7,
141.4, 136.4, 136.3, 132.7, 129.3, 128.6, 119.7, 110.1, 35.4, 27.5,
26.7. Anal. Calcd (%) for C15H15NO2: C, 74.67; H, 6.27; 5.81.
Found: C, 73.92; H, 6.33; N, 5.40. HRMS (ESI+): m/z [M + H+]
calcd for C15H15NO2: 242.118; Found: 242.172.
(16) 1-Methyl-5-(m-tolyl)-1H-pyrrole-2-carbaldehyde (7d)
The reaction of 3-bromotoluene (0.060 mL, 1 mmol), 1-methyl-
2-formylpyrrole (0.100 ml, 2 mmol), and KOAc (0.098 g, 2
mmol) with Pd@PPy (0.003 g, 2 mol%) affords the correspond-
ing product 7d in 41% isolated yield. 1H NMR (300 MHz, CDCl3):
δ = 9.57 (s, 1 H), 7.37–7.32 (m, 1 H), 7.26–7.20 (m, 3 H), 6.96
(dd, J = 4.1 Hz, 1 H), 6.29 (d, J = 4.1 Hz, 1 H), 3.93 (s, 3 H), 2.41 (s,
3 H). 13C NMR (75 MHz, CDCl3): δ = 179.5, 144.6, 138.4, 133.0,
131.1, 129.9, 129.4, 128.5, 126.3, 124.5, 110.7, 34.4, 21.5. Anal.
Calcd (%) for C13H13NO: C, 78.36; H, 6.58; N, 7.03. Found: C,
77.93; H, 6.53; N, 6.70. HRMS (ESI+): m/z [M + H+] calcd for
C
13H13NO: 200.107; found: 200.190.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, 1227–1231