Three-component coupling synthesis of diversely substituted n-aryl pyrroles catalyzed by iron(III) chloride

Article abstract of DOI:10.1080/00397911.2011.650273

An efficient and operationally simple three-component coupling synthesis of varieties of N-aryl substituted pyrroles is described in the presence of sustainable and environmentally benign metal catalyst, FeCl3. This method provides a straightforward approach for the synthesis of N-aryl substituted pyrroles in good yields from easily accessible starting materials such as nitroalkenes, 1,3-dicarbonyl compounds, and primary aromatic amines. The reaction proceeds through a catalytic sequence of Fe(III)-catalyzed amination/ Michael/cycloisomerization reactions. Supplemental materials are available for this article. Go to the publisher's online edition of Synthetic Communications1 to view the free supplemental file. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397911.2011.650273

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Three-Component Coupling Synthesis
of Diversely Substituted N-Aryl Pyrroles
Catalyzed by Iron(III) Chloride
Soumen Sarkar a , Krishnendu Bera a , Sukhendu Maiti a , Srijit
Biswas a & Umasish Jana a
a Department of Chemistry, Jadavpur University, Kolkata, West
Bengal, India
Accepted author version posted online: 29 May 2012.Version of
record first published: 06 Mar 2013.
To cite this article: Soumen Sarkar , Krishnendu Bera , Sukhendu Maiti , Srijit Biswas & Umasish Jana
(2013): Three-Component Coupling Synthesis of Diversely Substituted N-Aryl Pyrroles Catalyzed by
Iron(III) Chloride, Synthetic Communications: An International Journal for Rapid Communication of
Synthetic Organic Chemistry, 43:11, 1563-1570
To link to this article: http://dx.doi.org/10.1080/00397911.2011.650273
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Synthetic Communications1, 43: 1563–1570, 2013
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2011.650273
THREE-COMPONENT COUPLING SYNTHESIS
OF DIVERSELY SUBSTITUTED N-ARYL PYRROLES
CATALYZED BY IRON(III) CHLORIDE
Soumen Sarkar, Krishnendu Bera, Sukhendu Maiti,
Srijit Biswas, and Umasish Jana
Department of Chemistry, Jadavpur University, Kolkata, West Bengal, India
GRAPHICAL ABSTRACT
Abstract An efficient and operationally simple three-component coupling synthesis of
varieties of N-aryl substituted pyrroles is described in the presence of sustainable and envir-
onmentally benign metal catalyst, FeCl3. This method provides a straightforward approach
for the synthesis of N-aryl substituted pyrroles in good yields from easily accessible starting
materials such as nitroalkenes, 1,3-dicarbonyl compounds, and primary aromatic amines.
The reaction proceeds through a catalytic sequence of Fe(III)-catalyzed amination/
Michael/cycloisomerization reactions.
Supplemental materials are available for this article. Go to the publisher’s online edition
of Synthetic Communications1 to view the free supplemental file.
Keywords Iron; multicomponent; N-aryl pyrrole; sustainable; tandem
INTRODUCTION
Polysubstituted pyrroles are an important class of N-heterocycles that are
frequently found in many natural products,[1] pharmaceutically active compounds,[2]
and various kinds of functional materials.[3] Among the various substitution patterns
of pyrroles, N-aryl pyrrole–containing compounds exhibit a wide array of biological
activities such as antimycobacterial,[4] anticonvulsant,[5] anticancer,[6] anti-HIV,[7]
analgesic, and anti-inflammatory activities.[8] Moreover, N-aryl pyrroles are very
Received August 26, 2011.
Address correspondence to Umasish Jana, Department of Chemistry, Jadavpur University,
Kolkata 700 032, West Bengal, India. E-mail: jumasish2004@yahoo.co.in
1563

1564
S. SARKAR ET AL.
important building blocks for further synthetic transformations[9] and are important
in material and surface chemistry.[10] Therefore, considering their importance in
pharmacology and functional materials, the synthesis of libraries of N-aryl pyrroles
is highly desirable. Although many methods are available for the synthesis of substi-
tuted pyrroles, relatively few methods have been developed for the synthesis of
N-aryl pyrroles. The most common and traditional methods are classical and modi-
fied Paal–Knorr reactions of cyclocondensation of 1,4-diketones with aromatic
amines.[11] Recently, transition metal–catalyzed N-arylation of pyrrole with aryl
halide have received much attention. To date, a few copper-catalyzed Ullmann-type
coupling reactions have been reported.[12] However, these reports generally suffer
from several drawbacks such as high reaction temperatures (often 140 ꢀC or greater)
and poor substrate generality, and they work in the presence of diamine or with
other ligands. Although N-arylation of electron-deficient pyrroles has been reported
by cross-coupling with arylboronic acids at room temperature, in this reaction 1.5
equiv. of Cu(OAc)2 and 2.0 equiv. of pyridine have been used.[13]
Very recently, Liao et al. reported CuI-mediated double N-vinylation of aromatic
amines in the presence of diamine ligands to access N-aryl pyrroles.[14] Yan et al.
reported CuI-catalyzed oxidative cyclization of b-enamino ketones or esters and dialkyl
ethylenedicarboxylate in the presence of oxygen for the synthesis of N-aryl pyrroles.[15]
Galliford and Scheidt demonstrated Rh(II) salt–catalyzed three-component coupling
of an imine, diazoacetonitrile, and dialkyl ethylenedicarboxylate.[16] A convenient
zinc(II) chloride–catalyzed regioselective process for the synthesis of N-aryl pyrrole
derivatives from propargylic acetates, enoxysilanes, and primary amines[17] has been
described by Liu et al. Bian et al. explored Pd(II) salt–catalyzed tandem intermolecular
amination and intermolecular hydroamintion reaction for N-aryl pyrrole.[18]
However, all these methods suffer from generality, unavailability of the starting
materials, and use of toxic and expensive transition metal catalysts. Therefore, to build
up a library of N-aryl-substituted pyrroles for the study of their biological activities, the
development of efficient, selective, sustainable, and operationally simple routes for
rapid access to functionalized N-aryl pyrrole under mild conditions is in high demand.
In this regard, a metal-catalyzed multicomponent reaction (MCR) for the
synthesis of substituted pyrroles is a very appealing strategy,[19] because it offers
rapid and convergent construction of complex molecules without the need of iso-
lation and purifications of any intermediates, resulting in substantial minimization
of waste, labor, time, and cost. As part of our ongoing research program toward
the development of a novel sustainable reaction for the synthesis of heterocycles
catalyzed by iron salts,[19b,20] we describe herein an efficient tandem reaction for
the synthesis of N-aryl-substituted pyrroles, through a one-pot, three-component
coupling reaction of easily accessible starting materials such as nitroalkenes,
1,3-dicarbonyl compounds, and aromatic primary amine. This reaction would pro-
ceed through a tandem amination=Michael=cycloisomerization reaction (Scheme 1).
RESULTS AND DISCUSSION
To optimize the reaction conditions, a set of reactions in different solvents and
temperature was performed using easily accessible nitroalkene 1a, 1,3-dicarbonyl
compound 2a, and aromatic amine 3a in the presence of catalytic FeCl3. The results

IRON-CATALYZED N-ARYL PYRROLE SYNTHESIS
1565
Scheme 1. Strategy for FeCl3-catalyzed three-component coupling synthesis of pyrroles.
Table 1. Optimization of reaction conditions for the iron-salt-catalyzed three-component coupling
reactiona
Entry
Solvent
Catalyst
Time (h)
T (ꢀC)
Yield (%)b
1
2
Dichloromethane
Dichloroethane
Acetonitrile
FeCl3 (5 mol%)
FeCl3 (5 mol%)
FeCl3 (5 mol%)
FeCl3 (5 mol%)
FeCl3 (5 mol%)
FeCl3 (5 mol%)
FeCl3 (5 mol%)
FeCl3 (5 mol%)
FeCl3 (10 mol%)
FeBr3 (5 mol%)
Fe(acac)3 (5 mol%)
Fe(OTf)3 (5 mol%)
8
8
8
8
8
8
8
8
8
8
8
8
8
8
40
85
6
14
41
25
68
52
55
88
88
54
29
44
58
38
3
85
70
4
Tetrahydrofuran
Toluene
Ethanol
5
110
70
6
7
Nitromethane
Nitromethane
Nitromethane
Nitromethane
Nitromethane
Nitromethane
Nitromethane
Nitromethane
75
8
100
100
100
100
100
100
100
9
10
11
12
13
14
.
FeCl3 6H2O (5 mol%)
InCl3 (5 mol%)
aAll reactions were carried out using nitroalkene (1 mmol), 1,3-dicarbonyl compounds (1 mmol), and
aromatic amines (1.5 mmol) with solvent (1 mL).
bYield obtained after column chromatography.
are summarized in Table 1. It was observed that the yield of the desired product was
highly depended on the nature of solvents and the reaction temperatures. The most
effective solvent for this transformation was found to be nitromethane and gave 88%
yield under heating at 100 ꢀC for 8 h in the presence of FeCl3 (5 mol%). The reaction
without FeCl3 only gave 12% of the desired product after refluxing 30 h. This result
clearly indicated the participation of FeCl3 in various steps of this reaction. We have
tested other iron salts, such as FeBr3, Fe(acac)3, FeCl3 Á 6H2O, and Fe(OTf)3, and the
most effective one was anhydrous FeCl3. Under similar reaction conditions InCl3

1566
S. SARKAR ET AL.
gave only 38% of desired product. The optimized reaction condition of this 3CR was
very simple and straightforward. The mixture of nitroalkene (1 mmol), 1,3-dicarbonyl
compound (1 mmol), and aromatic amine (1.5 mmol) in nitromethane solvent (1 mL)
was heated at 100 ꢀC in the presenceof FeCl3(5 mol%) with a certain period of time
without an inert atmosphere. After completion of the reaction (by thin-layer chroma-
tography, TLC), the excess solvent was removed under vacuum and the crude product
was directly subjected to column chromatography to afford the pure substituted N-aryl
pyrrole. To test the versatility of this reaction, a number of substrates were investigated
under these reaction conditions. The results are summarized in Table 2. In general, the
FeCl3-catalyzed 3CR proceeded efficiently with varieties of nitroalkenes, 1,3-dicarbo-
nyl compounds, and aromatic amines in good yields within a few hours, as shown in
Table 2. Substituted aromatic amines bearing electron-donating groups and weakly
electron-withdrawing groups were suitable for this tandem reaction. For example,
p-MeO (3b) and p-Me (3c) proceeded well under this reaction conditions and gave
good yields of the desired pyrroles. Likewise, electron-deficient aromatic amines such
as p-Cl (3 g), o- and p-Br (3d and 3 h), and p-F (3j) anilines underwent smooth reactions
with a wide variety of nitroalkenes and 1,3-dicarbonyl compounds and gave compara-
ble yields. It is noteworthy that this reaction worked even for sterically hindered
aromatic amines such as o-bromoaniline and o-bromo-p-toludine and gave good yields
of the desired products. These halogen-bearing substrates are very useful for further
functionalization, such as these can be used for various cross-coupling reactions.
For example, compound 4f successfully underwent Sonogashira coupling with pheny-
lacetylene and the product 5a was obtained 75% yield (Scheme 2).
Moreover, 2-naphthyl amine 3e also reacted under the optimized condition and
gave good yield of the desired pyrrole. Interestingly, anilines bearing strong
electron-withdrawing groups at the ortho-position such as –CO2Me also participated
in this reaction and gave the expected product in 45% yield. The poor yield of the pro-
duct is attributed to the steroelectronic factor. It is worth mentioning that this substrate
can be further utilized by simple manipulation to synthesize N-bridgehead pyrrole.[9]
With respect to nitroalkene, a wide range of substrates were subjected to the
FeCl3-catalyzed tandem enaminoketone or ester=Michael=cycloisomerization reactions
to furnish the substituted N-aryl pyrroles. The reaction was compatible with varieties
of functional groups such as p-MeO, p-Me, p-Cl, and o-Br on the phenyl ring at the b-
position of nitrostyrene and underwent effective conversion to the desired products. Fur-
thermore, 2-naphthyl nitroalkene 1i, acetylacetone 2a, and aniline 3b were also efficiently
coupled to afford the 2-naphthyl substituted pyrrole (Table 2, entry 25) in good yield.
Remarkably, this tandem reaction was also suitable for disubstituted nitro-
alkene (Table 2, entries 13–15, 23–24, and 26) with different aromatic amines to
give the highly substituted N-aryl pyrroles in good yields without any dificulties.
Moreover, thiophene-substituted nitroalkene 1c (Table 2, entry 12), acetylacetone
2a, and p-toluidine 3c, when reacted under these conditions, gave the desired hybrid
heterocycle 4 l in 71% yield. Thus, this tandem reaction accommodated comfortably
a range of substrates with respect to all of the components.
Although the exact role of iron(III) chloride is not known yet, it probably behaves
as multifunctional Lewis acid catalyst. First it activates the carbonyl groups of
1,3-dicarbonyl compounds for effective generation of b-enaminocarbonyl compounds,
which we have observed as intermediates in this reaction. Then this b-enaminocarbonyl

IRON-CATALYZED N-ARYL PYRROLE SYNTHESIS
1567
Table 2. FeCl3-catalyzed three-component coupling synthesis of N-aryl pyrroles 4 from nitrostyrene 1,
1,3-dicarbonyl compounds 2, and aromatic primary amines 3a
Entry
R1, R2
R3, R4
R5
Time (h)
Products
Yield (%)b
1
2
Ph,H
1a
1a
Me, Me
2a
Ph
3a
8
8
4a
4b
88
81
Me, 0Me
2b
p-0MeC6H4
3b
3b
3
4
1a
1a
Ph, Me
2c
12
9
4c
4d
72
89
Me, 0Et
2d
2a
p-MeC6H4
3c
5
6
1a
1a
3b
o-BrC6H4
9
9
4e
4f
86
74
2a
3d
3d
7
8
1a
1a
2b
2a
9
10
4g
4h
66
70
2-Naphthyl
3e
o-Me0C0-C6H4
9
10
11
1a
2a
2a
9
8
4i
4j
45
78
3f
p-Cl-C6H4
p-Me-C6H4,H
1b
1b
3g
3c
3c
2a
2a
8
8
4k
4l
72
71
12
13
p-0Me-C6H4,Me
1d
2d
3b
11
4m
70
14
15
16
1d
1d
2d
2d
2b
3g
3a
9
9
4n
4o
4p
81
70
78
p-Cl-C6H4,H
1e
p-Br-C6H4
10
3h
3b
3b
3h
17
18
19
1e
1e
2c
2a
2a
9
10
7
4q
4r
4s
69
71
84
p-0Me-C6H4,H
1f
1f
20
21
2a
2a
8
9
4t
67
74
1f
p-F-C6H4
3j
4u
22
23
24
25
o-Br-C6H4,H 1g
Ph,Me 1h
2a
2c
2a
2a
3c
3c
3g
3b
9
10
11
12
4v
4w
4x
4y
73
69
66
70
1h
2-Naphthyl,H
1i
p-Cl-C6H4,Me
1j
26
2a
3c
8
4z
60
aAll reactions were carried out using nitroalkene (1 mmol), 1,3-dicarbonyl compounds (1 mmol), and
aromatic amines (1.5 mmol) in nitromethane (1 mL) at 100 ꢀC.
bYield obtained after column chromatography.

1568
S. SARKAR ET AL.
Scheme 2. Representative example for Sonogashira coupling.
compound undergoes FeCl3-catalyzed Michael and cycloisomerization reactions with
nitroalkenes, leading to pyrrole with loss of water and HNO. To prove this, a b-enam-
inocarbonyl compound of acetylacetone 2a and aniline 3a was prepared and reacted
with nitrostyrene 1a with and without FeCl3. It was observed that with FeCl3 the reac-
tion was completed within 1.5 h with comparable yield; however, without catalyst after
28h only 15% yield of the desired product was obtained.
Although a few related reactions including our work have been developed
earlier, many of them either did not work or were less efficient for the synthesis of
N-aryl pyrrole.[19b,21] Moreover, these reported methods were only suitable for alkyl
substituted pyrroles, but the present method can introduce alkyl, aryl, ketone, and
ester groups onto the pyrrole ring.
CONCLUSIONS
In summary, we have developed an efficient and one-pot FeCl3-catalyzed
three-component coupling synthesis of tri- and tetra-substituted N-aryl pyrroles
through tandem amination=Michael=cycloisomerization reactions. In this protocol
various substituted anilines were suitable for the generation of libraries of various
N-aryl pyrroles. This methodology provides a simple route to synthesize a wide
variety of tri- and tetra-substituted N-aryl pyrroles in good yields from easily access-
ible starting materials. The broad scope and experimental simplicity of this method
have made it a better alternative than the existing methods. Moreover, the use of
sustainable iron-salt makes this methodology highly attractive in modern green
organic synthesis. Further development and application toward the complex
molecule using this methodology is currently under way in our laboratory.
EXPERIMENTAL
Anhydrous FeCl3 (8 mg, 0.05 mmol) was added to a stirred solution of acetyl
acetone 2a (100 mg, 1 mmol), (2-nitrovinyl)benzene 1a (149 mg, 1 mmol), and aniline
3a (139 mg, 1.5 mmol) in nitromethane solvent (1 mL). The mixture was heated to
reflux slowly for a set period of time and then cooled down to room temperature.
The excess solvent was removed under vacuum, and the residue was directly purified
by silica-gel column chromatography to afford the product 4a (242 mg, 0.88 mmol,
88%) as a yellow solid.

IRON-CATALYZED N-ARYL PYRROLE SYNTHESIS
1569
ACKNOWLEDGMENTS
We gratefully acknowledge the financial and infrastructural support from
the University Grants Commission (UGC)–CAS program of the Department of
Chemistry, Jadavpur University. The Department of Science and Technology
(DST)–PURSE program is also gratefully acknowledged. S. S. and K. B. are thank-
ful to the Council of Scientific and Industrial Research (CSIR), New Delhi, India,
for their fellowships. S. M. and S. B. are also thankful to the UGC, New Delhi,
Jadavpur University, New Delhi, India, respectively, for their fellowships.
REFERENCES
1. Fan, H.; Peng, J.; Hamann, M. T.; Hu, J.-F. Lamellarins and related pyrrole-derived
alkaloids from marine organisms. Chem. Rev. 2008, 108, 264–287.
2. (a) Kidwai, M.; Venkataramanan, R.; Mohan, R.; Sapra, P. Cancer chemotherapy and
heterocyclic compounds. Curr. Med. Chem. 2002, 9, 1209–1228; (b) Bode, H. B.; Irschik,
H.; Wenzel, S. C.; Reichenbach, H.; Mueller, R.; Hoefle, G. The leupyrrins: A structurally
unique family of secondary metabolites from the myxobacterium sorangium cellulosum.
J. Nat. Prod. 2003, 66, 1203–1206; (c) Huffman, J. W.; Padgett, L. W. Recent develop-
ments in the medicinal chemistry of cannabimimetic indoles, pyrroles, and indenes. Curr.
Med. Chem. 2005, 12, 1395–1411.
3. Higgins, S. J. Conjugated polymers incorporating pendant functional groups—Synthesis
and characterisation. Chem. Soc. Rev. 1997, 26, 247–257.
4. (a) Biava, M.; Rossella, F.; Giulio, C. P.; Delia, D.; Carlo, M.; Pompei, R. 2-Naphthyl-
carbapenems: Broad-spectrum antibiotics with enhanced potency against MRSA. Bioorg.
Med. Chem. Lett. 1999, 9, 2893–2988; (b) Sorokina, I. K.; Andreeva, N. I.; Golovina, S.
M. Synthesis and anticonvulsant activity of 3-dimethylaminomethyl-8-oxoindeno-
[2,1-b]pyrroles. Pharm. Chem. J. 1989, 23, 975–977.
5. Carson, J. R.; Carmosin, R. J.; Pitis, P. M.; Vaught, J. L.; Almond, H. R.; Stables, J. P.;
Wolf, H. H.; Swinyard, E. A.; White, H. S. Aroyl(aminoacyl)pyrroles, a new class of
anticonvulsant agents. J. Med. Chem. 1997, 40, 1578.
6. Maria, T. C.; Cenzo, C. Valentina, O. Synthesis and in vitro antitumoral activity of new
N-phenyl-3- pyrrolecarbothioamides. Bioorg. Med. Chem. 2003, 11, 495–503.
7. Shibo, J.; Hong, L.; Shuwen, L.; Qian, Z.; Yuxian H.; Asim, K. N-Substituted pyrrole
derivatives as novel human immunodeficiency virus type 1 entry inhibitors that interfere
with the gp41 six-helix bundle formation and block virus fusion. Antimicrob Agents
Chemother. 2004, 48, 4349–4359.
8. (a) Malinka, W.; Dziuba, M. S.; Rajtar, G.; Rubaj, A.; Kleinrok, Z. Synthesis and
pharmacological screening of some N-(4-substituted-piperazin-1-ylalkyl)-3,4-pyrro-
ledicarboximides. Farmaco 1999, 54, 390–401; (b) Malinka, W.; Kaczmarz, M.; Redzicka,
A.; Filipek, B.; Sapa, J. Synthesis and analgesic action of N-(substituted-ethyl)pyrrole-
3,4-dicarboximides. Farmaco 2005, 60, 15–22.
9. (a) Hwang, S. J.; Cho, S. H.; Chang, S. Synthesis of condensed pyrroloindoles via
Pd-catalyzed intramolecular C-H bond functionalization of pyrroles. J. Am. Chem. Soc.
2008, 130, 16158–16159, and reference cited therein.
10. Gallopini, E. Linkers for anchoring sensitizers to semiconductor nanoparticles. Coord.
Chem. Rev. 2004, 248, 1283–1297.
11. (a) Banik, B. K.; Samajder, S.; Banik, I. Simple synthesis of substituted pyrroles. J. Org.
Chem. 2004, 69, 213–216, and reference cited therein; (b) Biavaa, M.; Porrettaa, G. C.;
Giorgia, G.; Sleiterb, G. b-Aminomethylation of N-aryl and N-azaheteroaryl-substituted

1570
S. SARKAR ET AL.
methyl 2,5-dimethylpyrrole-3-carboxylates: Kinetic effect of the N-pyrrole substituent.
Arkivoc 2004, 325–333.
12. (a) Kim, A. Y.; Lee, H. J.; Park, J. C.; Kang, H.; Yang, H.; Song, H.; Park, K. H. Highly
efficient and reusable copper-catalyzed N-arylation of nitrogen-containing heterocycles
with aryl halides. Molecules 2009, 14, 5169–5178; (b) Klapars, A.; Antilla, J. C.; Huang,
X.; Buchwald, S. L. A general and efficient copper catalyst for the amidation of aryl
halides and the N-arylation of nitrogen heterocycles. J. Am. Chem. Soc. 2001, 123,
7727–7729; (c) Ma, H.-C.; Jiang, X.-Z. N-Hydroxyimides as efficient ligands for the
copper-catalyzed N-arylation of pyrrole, imidazole, and indole. J. Org. Chem. 2007, 72,
8943–8946, and reference cited therein; (d) Antilla, J. C.; Baskin, J. M.; Barder T. E.;
Buchwald, S. L. Copper-diamine-catalyzed N-arylation of pyrroles, pyrazoles, indazoles,
imidazoles, and triazoles. J. Org. Chem. 2004, 69, 5578–5587.
13. Yu, S.; Saenz, J. Srirangam, J. K. Facile synthesis of N-aryl pyrroles via Cu(II)-mediated
cross coupling of electron-deficient pyrroles and arylboronic acids. J. Org. Chem. 2002, 67,
1699–1702.
14. Liao, Q.; Zhang, L.; Wang, F.; Li, S.; Xi, C. Copper-catalyzed double N-vinylation of
aromatic amines: An efficient synthesis of various substituted N-arylpyrroles. Eur. J.
Org. Chem. 2010, 1, 5426–5431.
15. Yan, R.-L.; Luo, J.; Wang, C.-X.; Ma, C.-W.; Huang, G.-S.; Liang, Y.-M.
Cu(I)-catalyzed synthesis of polysubstituted pyrroles from dialkyl ethylenedicarboxylates
and b-enamino ketones or esters in the presence of O2. J. Org. Chem. 2010, 75, 5395–5397.
16. Galliford, C. V.; Scheidt, K. A. Catalytic multicomponent reactions for the synthesis of
N-Aryl trisubstituted pyrroles. J. Org. Chem. 2007, 72, 1811–1813.
17. Liu, X.-T.; Hao, L.; Lin, M.; Chen, L. Zhan, Z.-P. One-pot highly efficient synthesis of
substituted pyrroles and N-bridgehead pyrroles by zinc-catalyzed multicomponent
reaction. Org. Biomol. Chem. 2010, 8, 3064–3072.
18. Bian, Y.-J.; Liu, X.-Y.; Ji, K.-G.; Shu, X.-Z.; Guo, L.-N.; Liang, Y.-M. Efficient synthesis
of highly substituted pyrroles based on the tandem reactions: Intermolecular amination
and Pd(II)-catalyzed intramolecular hydroamidation. Tetrahedron 2009, 65, 1424–1429.
´
´
19. (a) For a recent review, see, Estevez, V.; Villacampa, M.; Menendez, J. C. Multicompo-
nent reactions for the synthesis of pyrroles. Chem. Soc. Rev. 2010, 39, 4402–4421, and
references cited therein; (b) Balme, G. Pyrrole synthesis by multicomponent coupling reac-
tions. Angew. Chem. Int. Ed. 2004, 43, 6238–6241; (c) Maiti, S.; Biswas, S.; Jana, U.
Iron(III)-catalyzed four-component coupling reaction of 1,3-dicarbonyl compounds,
amines, aldehydes, and nitroalkanes: A simple and direct synthesis of functionalized
pyrroles. J. Org. Chem. 2010, 75, 1674–1683, and references cited therein.
20. (a) Jana, U.; Maiti, S.; Biswas, S. An FeCl3-catalyzed highly C3-selective Friedel–Crafts alky-
lation of indoles with alcohols. Tetrahedron Lett. 2007, 48, 7160–7163; (b) Bera, K.; Sarkar,
S.; Biswas, S.; Maiti, S.; Jana, U. Iron-catalyzed synthesis of functionalized 2H-chromenes
via intramolecular alkyne carbonyl metathesis. J. Org. Chem. 2011, 76, 3539–3544.
21. (a) Meyer, H. Heterocyclen aus Nitroalkenen, I: Pyrrole durch cyclisierende Michael
addition von Enaminen. Liebigs Ann. Chem. 1981, 1534–1544; (b) Shiraishi, H.; Nishitani,
T.; Sakaguchi, S.; Ishii, Y. Preparation of substituted alkylpyrroles via samarium-
catalyzed three-component coupling reaction of aldehydes, amines, and nitroalkanes.
J. Org. Chem. 1998, 63, 6234–6238; (c) Ranu, B. C., Hajra, A.; Jana, U. Microwave-
assisted synthesis of substituted pyrroles by a three-component coupling of a, b-unsatu-
rated carbonyl compounds, aliphatic amines, and nitroalkanes on the surface of silica
gel. Synlett 2000, 75; (d) Alizadeh, A.; Rezvanian, A.; Bijanzadeh, H. R. synthesis of
highly functionalized pyrrole derivatives via a four-component reaction of two primary
amines and diketene in the presence of nitrostyrene. Synthesis 2008, 725–728.