An efficient one-pot synthesis of tetra-substituted pyrroles

Article abstract of DOI:10.1016/j.tet.2011.05.076

The three-component reaction of primary amines, dialkyl acetylenedicarboxylates and β-nitrostyrene derivatives in the presence of Iron(III) chloride afforded 1,2,3,4-tetra-substituted pyrroles in high yields. These reactions could precede via domino Micha

Full text of DOI:10.1016/j.tet.2011.05.076

Tetrahedron 67 (2011) 5415e5420
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
An efficient one-pot synthesis of tetra-substituted pyrroles
,
a
b
c
Elmira Ghabraie a, Saeed Balalaie a , Morteza Bararjanian , Hamid Reza Bijanzadeh , Frank Rominger
*
a Peptide Chemistry Research Center, K.N. Toosi University of Technology, PO Box 15875-4416, Tehran, Iran
b Department of Chemistry, Tarbiat Modares University, PO Box 141115-175, Tehran, Iran
c
€
Organisch-Chemisches Institut der Universitat Heidelberg, Im Neuenheimer Feld 270, D-69120 Heidelberg, Germany
a r t i c l e i n f o
a b s t r a c t
Article history:
The three-component reaction of primary amines, dialkyl acetylenedicarboxylates and
b
-nitrostyrene
Received 10 March 2011
Received in revised form 1 May 2011
Accepted 16 May 2011
derivatives in the presence of Iron(III) chloride afforded 1,2,3,4-tetra-substituted pyrroles in high yields.
These reactions could precede via domino Michael addition/cyclization process.
Ó 2011 Elsevier Ltd. All rights reserved.
Available online 25 May 2011
Dedicated to Prof. A. Rustaiyan on the
occasion of his 85th birthday
Keywords:
Tetra-substituted pyrrole
Iron(III) chloride
b
-Nitrostyrene
One-pot three-component reaction
Enaminone
1. Introduction
chloride to synthesis of 1,2,3,5-tetra-substituted pyrroles.18 Mean-
while, there are various pyrrole synthesis in the litratures.19e24
Pyrroles and their derivatives are one of the most important class
of heterocyclic compounds.1 They have extensive biological activities
and pharmacological properties.2 Many pyrrole derivatives exhibit
interesting biological properties, such as anti-bacterial,3 anti-in-
flammatory,4 anti-oxidant,5 anti-tumor, anti-fungal,6 and immune
suppressant activities.7 Highly functionalized pyrroles are subunits
However a number of methods have some drawbacks, such as
harsh reaction conditions, tedious experimental procedures, long
reaction time, and low yields.25 Although a number of methods are
available as cited above, the search for newer, more efficient
methods for the synthesis of pyrroles is currently being pursued.
b-Nitrostyrene and its derivatives are useful synthetic in-
of considerable importance in heme, chlorophyll, bile pigments, vi-
termediates and starting materials for the synthesis of a variety of
useful building blocks.26 According to their high potential for the
synthesis, and in continuation of our research toward novel mul-
ticomponent reactions for the synthesis of heterocyclic skeletons,27
we wish to report herein, the efficient one-pot three-component
8
tamin B12
,
and marine source-derived pyrrole alkaloids. Some
characteristic examples of these compounds with their biological
activities are shown in Fig. 1.9,10 Atrovastatin (Lipitor) is a drug for
lowering the cholesterol.11
There have been considerable studies on the effects of sub-
stituents and the design of the pyrrole skeleton, which contain
active substituents. The development of new and efficient methods
for their synthesis remains an area of current interest. Many syn-
thetic methods have been employed for the synthesis of pyrroles
including Knorr,12 PaaleKnorr,13 Hantzsch synthesis,14 1,3-dipolar
cycloaddition reactions,15 reductive coupling,16 and aza-Wittig re-
actions.17 Recently, Das et al. reported three-component reaction of
amines, DMAD, and phenacyl bromide catalyzed by Iron(III)
reaction of primary amines, dialkyl acetylenedicarboxylates, and b-
nitrostyrene derivatives in the presence of FeCl3, which leads to
1,2,3,4-tetra-substituted pyrroles in high yields (Scheme 1).
2. Results and discussions
We began our investigation with b-nitrostyrene 3a, which was
synthesized according to the reported method.28 The reaction of 3a
with benzylamine and dimethyl acetylenedicarboxylate was se-
lected as the model reaction. Heating of the mixture in toluene in
the presence of 40 (mol %) CuI for 72 h did not provide our goal and
the mixture of E and Z of enaminones was obtained. After this
* Corresponding author. E-mail address: balalaie@kntu.ac.ir (S. Balalaie).
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.05.076

5416
E. Ghabraie et al. / Tetrahedron 67 (2011) 5415e5420
Atorvastatin (Lipitor)
Chlorfenapyr (insecticide)
Pentaboromopseudilin
(antibacterial)
Fig. 1. Molecular structure of some biologically active compounds contained pyrrole skeleton.
CO2R2
Ar
CO2R2
CO2R2
in the model reaction. The reaction was checked without FeCl3 as
NO2
catalyst, and we did not get any product. In the presence of 10, 20,
30, and 40% of FeCl3, the yield of tetra-substituted pyrrole 4a
obtained was 40, 48, 70, and 85%, respectively. This shows the
important role of FeCl3 in this reaction. The optimum reaction
condition used of 40% FeCl3 and boiling toluene as reaction
medium.
FeCl3 (40 mol%)
Toluene, Reflux
R1
NH2
CO2R2
N
R
Ar
R = Me, Et
1 a-e
3 a-g
Scheme 1.
2 a, b
4 a-p
(75-95%)
In an attempt to investigate the range of solvents compatible
with this reaction, b-nitrostyrene 3a and enaminone from reaction
of benzylamine and dimethyl acetylendicarboxylate were chosen
for a model system, and this reaction was performed in various
solvents. A change in the solvent to dichloromethane, ethanol,
acetonitrile, and toluene gave pyrrole 4a in 16e85% yield. In eth-
anol and acetonitrile, the reaction had low yield. The best yield for
reaction model was obtained in toluene.
After finding suitable conditions, the three-component reaction
of b-nitrostyrenes, dialkyl acetylenes, and also primary amines for
the synthesis of tetra-substituted pyrroles were studied. The results
summarized in Table 1.
failure, we tried various Lewis acids; such as ZrO2, ZrCl4, and the
desired product did not achieved. Recently, Iron(III) chloride was
used as an efficient catalyst for the synthesis of carboneheteroatom
and heteroatomeheteroatom linkages with high valuable advan-
tages.29 We only got satisfactory results ZnCl2 and FeCl3. The best
result was obtained with FeCl3. According to this result, FeCl3 was
selected as the best catalyst for the synthesis of tetra-substituted
pyrroles. Then the catalytic amount of this catalyst was examined
Table 1
Synthesis of tetra-substituted pyrroles using b-nitrostyrene
Amine
b
-Nitrostyrene
Product
Amine
b
-Nitrostyrene
Product
BneNH2
1a
BneNH2
1a
BneNH2
1a

E. Ghabraie et al. / Tetrahedron 67 (2011) 5415e5420
5417
Table 1 (continued )
Amine
b-Nitrostyrene
Product
Amine
b
-Nitrostyrene
Product
BneNH2
1a
BneNH2
1a
BneNH2
1a
BneNH2
1a
a
Isolated yields.
Reaction condition: b-nitrostyrene (1.0 mmol), amine (1.4 mmol), dialkyl acetylenedicarboxylate (1.4 mmol), FeCl3 (40%), and PhMe (reflux).
The structures of the products 4aep were deduced from their
HR-mass spectrometry and NMR spectroscopic data. The scope and
limitations of this three-component reaction were explored by
Iron(III) chloride could facilitate the remove of nitro group and also
formation of pyrrole moiety. Meanwhile, Fe(III) has an essential role
for the oxidation process to obtain the final product 3. Because of
kinetic facility, formation of five-membered ring is observed
(Scheme 2).
In conclusion, an efficient approach for the one-pot synthesis of
tetra-substituted polyfunctional pyrroles catalyzed by FeCl3 has
been developed. Easy work-up, synthesis of polyfunctional com-
pounds, which are ready for further reactions, and an easily avail-
able and less expensive catalyst, good to high yields are advantages
of the present method.
using primary amines and also different b-nitrostyrene derivatives.
Meanwhile, the structure of the products was confirmed according
to the X-ray crystallographic data. Fig. 2 shows the ORTEP structure
of the compound 4g.
The possible mechanism of this conversion was shown in
Scheme 2. This conversion involves the initial reaction of primary
amines with dimethyl acetylenedicarboxylate to form the desired
enaminone, then b-nitrostyrene could be activated by FeCl3 and
undergo the nucleophilic addition. The subsequent cyclization of
intermediate B followed by the elimination of the nitro group leads
to C. On the basis of the established chemistry of Iron(III) chemis-
try,30 it is reasonable to assume that Iron(III) chloride has an es-
3. Experimental section
Commercially available materials were used without further
purification. Melting points were determined on an Electrothermal
9100 apparatus and were uncorrected. IR spectra were obtained on
sential role in the addition of enaminone to
b-nitrostyrene via
coordination with oxygen lone pairs. Meanwhile, the presence of

5418
E. Ghabraie et al. / Tetrahedron 67 (2011) 5415e5420
3.1.1. Dimethyl 1-benzyl-4-phenyl-1H-pyrrole-2,3-dicarboxylate
(4a). Yellow oil (290 mg, 83%); Rf (25% EtOAC/hexane) 0.51; nmax
(neat): 1715 cmꢀ1
dH (500 MHz, CDCl3): 3.81 (3H, s, eCO2CH3), 3.85
;
(3H, s, eCO2CH3), 5.53 (2H, s, eCH2N), 6.97 (1H, s, ]CHpyrrole), 7.20
(2H, d, J 7.2 Hz, HeAr), 7.30 (2H, t, J 7.5 Hz, HeAr), 7.36 (4H, t, J
7.0 Hz, HeAr), 7.43 (2H, d, J 8.5 Hz, HeAr); dC (125 MHz, CDCl3):
51.8, 52.3, 52.4, 121.2, 122.3, 124.0, 125.7, 127.0, 127.2, 127.4, 127.9,
128.06, 128.8, 133.3, 137.1, 160.6, 167.2; HR-Mass (ESI) calcd for
C21H20NO4 [Mþ1]þ 350.1387, found 350.1387.
3.1.2. Diethyl 1-benzyl-4-phenyl-1H-pyrrole-2,3-dicarboxylate
(4b). Yellow oil (328 mg, 87%); Rf (25% EtOAC/hexane) 0.52; nmax
(neat): 1605, 1701, 1725, 2984 cmꢀ1
; dH (500 MHz, CDCl3): 1.30 (6H,
t, J 7.1 Hz, 2CH3), 4.27 (2H, q, J 7.1 Hz, eCH2), 4.32 (2H, q, J 7.1 Hz,
eCH2), 5.53 (2H, s, eCH2N), 6.95 (1H, s, ]CHpyrrole), 7.20 (2H, d, J
7.5 Hz, HeAr), 7.25e7.36 (6H, m, HeAr), 7.42 (2H, d, J 7.5 Hz, HeAr);
dC (125 MHz, CDCl3): 14.1, 52.4, 60.7, 61.3, 121.2, 122.6, 123.9, 125.5,
126.9, 127.3, 127.5, 127.8, 128.5, 128.8, 133.5, 137.1, 160.3, 166.8; HR-
Mass (ESI) calcd for C23H24NO4 [Mþ1]þ 378.1702, found 378.1701.
3.1.3. Dimethyl 1-benzyl-4-(4-bromophenyl)-1H-pyrrole-2,3-
dicarboxylate (4c). Yellow solid (378 mg, 83%); mp: 90e94 ꢁC; Rf
Fig. 2. ORTEP Structure of compound 4g.
(25% EtOAC/hexane) 0.45; nmax (neat): 1714 cmꢀ1
; dH (500 MHz,
R2O2C
HN
CO2R2
CO2R2
CO2R2
R2O2C
H
R1 NH2
NO2
R1
N
Ar
R1
CO2R2
N
O
O
FeCl3
B
CO2R2
CO2R2
CO2R2
Oxidation
Aromatization
CO2R2
N
R1
N
R1
Scheme 2. Possible mechanism for the synthesis of tetra-substituted pyrroles 4a.
an ABB FT-IR FTLA 2000 spectrometer. 1H NMR and 13C NMR
spectra were run on Bruker DRX-500 AVANCE spectrometers at
500 MHz for 1H NMR, and 125 MHz for 13C NMR. CDCl3 was used as
solvents. High resolution mass spectra were recorded on HR-MS
was recorded on Mass-ESI-POS (Apex Qe-FT- ICR instrument)
spectrometer.
CDCl3): 3.80 (3H, s, eOCH3), 3.82 (3H, s, eOCH3), 5.52 (2H, s,
eCH2N), 6.91 (1H, s, ]CHpyrrole), 7.19 (2H, d, J 7.5 Hz, HeAr), 7.25
(2H, d, J 7.0 Hz, HeAr), 7.29e7.36 (3H, m, HeAr), 7.46 (2H, d, J 7.0 Hz,
HeAr); dC (125 MHz, CDCl3): 51.8, 52.3, 52.5, 103.0, 121.6, 121.9,
123.0, 125.4, 127.3, 128.0, 128.8, 129.1, 131.6, 132.3, 136.7, 160.6,
166.8; HR-Mass (ESI) calcd for C21H1979BrNO4 [Mþ1]þ 428.0495,
found 428.0494; calcd for C21H1981BrNO4 [Mþ1]þ 430.0475, found
430.0474.
3.1. General procedure for the synthesis of dimethyl 1-alkyl-
4-aryl-1H-pyrrole-2,3-dicarboxylate (4aek)
3.1.4. Dimethyl 1-benzyl-4-(4-chlorophenyl)-1H-pyrrole-2,3-
dicarboxylate (4d). Yellow solid (386 mg, 94%); mp: 85e90 ꢁC; Rf
In a round bottom flask equipped with a magnetic stirrer, dialkyl
acetylenedicarboxylate (1.4 mmol) and primary amine (1.4 mmol)
in toluene (10 ml) were charged and the mixture was stirred vig-
(25% EtOAC/hexane) 0.47; nmax (KBr): 1703 cmꢀ1
; dH (500 MHz,
CDCl3): 3.80 (3H, s, eCO2CH3), 3.83 (3H, s, eCO2CH3), 5.52 (2H, s,
eCH2N), 6.92 (1H, s, ]CHpyrrole), 7.19 (2H, d, J 7.5 Hz, HeAr),
7.26e7.36 (7H, m, HeAr); dC (125 MHz, CDCl3): 51.8, 52.3, 52.5,
121.6, 122.0, 123.0, 125.4, 127.3, 128.0, 128.7, 128.8, 128.9, 131.8,
132.9, 136.7, 160.6, 166.9; HR-Mass (ESI) calcd for C21H19 35ClNO4
[Mþ1]þ 384.0998, found 384.0998; calcd for C21H1937ClNO4
[Mþ1]þ 386.0968, found 386.0968.
orously at room temperature. Then,
b-nitrostyrene derivatives
(1 mmol) and FeCl3 (40 mol %) were added to the mixture and the
mixture was heated under reflux conditions. The reaction was
completed after 5 h. The mixture was filtered and the solvent was
removed under reduced pressure. Further purification was done
using preparative TLC (eluent: hexane/EtOAc 3:1). In some cases,
further purification was done using recrystallization with mixture
of petroleum ether/dichloromethane.
3.1.5. Dimethyl 1-benzyl-4-(4-methoxyphenyl)-1H-pyrrole-2,3-
dicarboxylate (4e). Yellow oil (355 mg, 87%); Rf (25% EtOAC/

E. Ghabraie et al. / Tetrahedron 67 (2011) 5415e5420
5419
hexane) 0.43; nmax (neat): 1735 cmꢀ1
;
dH (500 MHz, CDCl3): 3.80
121.6, 123.3, 123.4, 124.1, 126.3, 127.1, 127.7, 127.8, 128.6, 128.7, 131.7,
132.7, 134.8, 141.7, 161.4, 165.6; HR-Mass (ESI) calcd for
(6H, s, eCO2CH3), 3.83 (3H, s, eOCH3), 5.51 (2H, s, eCH2N), 6.89 (1H,
s, ]CHpyrrole), 7.18 (2H, d, J 7.1 Hz, HeAr), 7.26e7.34 (5H, m,
HeAr); dC (125 MHz, CDCl3): 51.7, 53.0, 55.2, 114.1, 122.1, 123.8,
125.3, 125.8, 127.2, 127.8, 128.2, 128.6, 128.8, 129.0, 137.1, 158.8,
160.7, 167.3; HR-Mass (ESI) calcd for C22H22NO5 [Mþ1]þ 380.1494,
found 380.1494.
C
22H2179BrNO4 [Mþ1]þ 442.0653, found 442.0652; HR-Mass (ESI)
calcd for C22H2181BrNO4 [Mþ1]þ 442.0632, found 442.0631.
3.1.10. Dimethyl 4-(4-chlorophenyl)-1-(1-phenylethyl)-1H-pyrrole-
2,3-dicarboxylate (4j). Yellow oil (424 mg, 93%); Rf (25% EtOAC/
hexane) 0.46; nmax (neat): 1719 cmꢀ1
; dH (500 MHz, CDCl3): 1.83
3.1.6. Dimethyl 1-benzyl-4-p-tolyl-1H-pyrrole-2,3-dicarboxylate
(3H, d, J 7.0 Hz, eCH3), 3.80 (3H, s, eOCH3), 3.81 (3H, s, eOCH3), 6.45
(1H, q, J 7.0 Hz, eCHN), 7.0 (1H, s, ]CHpyrrole), 7.30 (4H, d, J 5.0 Hz,
HeAr), 7.20e7.40 (5H, m, HeAr); dC (125 MHz, CDCl3): 21.9, 39.5,
53.0, 53.4, 121.6, 122.2, 122.9, 126.4, 127.6, 127.7, 127.8, 128.7, 128.8,
128.9, 132.1, 132.8, 141.4, 160.8, 166.9; HR-Mass (ESI) calcd for
C22H2135ClNO4 [Mþ1]þ 398.1155, found 398.1154; calcd for
C22H2137ClNO4 [Mþ1]þ 400.1127, found 400.1126.
(4f). Yellow oil (345 mg, 95%); Rf (25% EtOAC/hexane) 0.54; nmax
(neat): 1714 cmꢀ1
; dH (500 MHz, CDCl3): 2.37 (3H, s, eCH3), 3.81
(3H, s, eCO2CH3), 3.85 (3H, s, eCO2CH3), 5.52 (2H, s, eCH2N), 6.95
(1H, s, ]CHpyrrole), 7.18 (2H, d, J 8.5 Hz, HeAr), 7.20 (2H, d, J 8.5 Hz,
HeAr), 7.29e7.36 (5H, m, HeAr); dC (125 MHz, CDCl3): 21.1, 51.7,
52.3, 52.4, 121.1, 122.3, 124.0, 125.6, 127.2, 127.3, 127.8, 128.8, 129.3,
130.4, 136.6, 137.1, 160.7, 167.3; HR-Mass (ESI) calcd for C22H22NO4
[Mþ1]þ 364.1545, found 364.1544.
3.1.11. Dimethyl 4-(4-methoxyphenyl)-1-(1-phenylethyl)-1H-pyrrole-
2,3-dicarboxylate (4k). Yellow oil (326 mg, 80%); Rf (25% EtOAC/
3.1.7. Dimethyl 1-benzyl-4-(3-nitrophenyl)-1H-pyrrole-2,3-
hexane) 0.41; nmax (neat): 1707 cmꢀ1
; dH (500 MHz, CDCl3): 1.84
dicarboxylate (4g). Yellow solid (323 mg, 82%); mp: 100e109 ꢁC;
(3H, d, J 7.0 Hz, eCH3), 3.80 (6H, s, eCO2CH3), 3.82 (3H, s, eCO2CH3),
6.47 (1H, q, J 7.0 Hz, eCHN), 6.90 (2H, d, J 6.0 Hz, HeAr), 6.97 (1H, s,
]CHpyrrole), 7.24 (2H, d, J 7.5 Hz, HeAr), 7.26e7.35 (5H, m, HeAr);
dC (125 MHz, CDCl3): 21.9, 51.7, 52.2, 55.2, 55.9, 114.0, 121.4, 121.8,
121.9, 123.8, 126.0, 126.4, 127.7, 128.6, 128.7, 141.6, 158.7, 160.9,
167.3; HR-Mass (ESI) calcd for C23H24NO5 [Mþ1]þ 394.1645, found
394.1646.
Rf (25% EtOAC/hexane) 0.44; nmax (KBr): 1727 cmꢀ1
; dH (500 MHz,
CDCl3): 3.82 (3H, s, eOCH3), 3.86 (3H, s, eOCH3), 5.54 (2H, s,
eCH2N), 7.02 (1H, s, ]CHpyrrole), 7.20 (2H, d, J 7.0 Hz, HeAr),
7.30e7.40 (3H, m, HeAr), 7.50 (1H, t, J 8.0 Hz, HeAr), 7.70 (1H, dd, J
8.0, 1.0 Hz, HeAr), 8.10 (1H, dt, J 7.0, 1.5 Hz, HeAr); dC (125 MHz,
CDCl3): 52.0, 52.4, 52.6, 121.6, 121.9, 122.3, 122.4, 122.5, 125.6, 127.3,
128.1, 128.9, 129.4, 133.4, 135.1, 136.4, 148.5, 160.6, 166.4; HR-Mass
(ESI) calcd for C21H19N2O6 [Mþ1]þ 395.1237, found 395.1237. Yel-
low crystal (plate), dimensions 0.36ꢂ0.20ꢂ0.06 mm3, crystal sys-
3.1.12. Dimethyl 1-(1-phenylethyl)-4-p-tolyl-1H-pyrrole-2,3-
dicarboxylate (4l). Yellow oil (313 mg, 80%); Rf (25% EtOAC/hex-
tem triclinic, space group P1, Z¼2, a¼9.0976 (2) A, b¼9.2228 (2) A,
ane) 0.52; nmax (neat): 1709 cmꢀ1
; dH (500 MHz, CDCl3): 1.85 (3H, d,
ꢀ
ꢀ
ꢀ
c¼11.7610 (1) A,
a
¼90.524 (1)ꢁ,
b
¼110.998 (1)ꢁ,
g
¼94.304 (1)ꢁ,
J 7.0 Hz, eCH3), 2.36 (3H, s, eCH3), 3.77 (3H, s, eCO2CH3), 3.84 (3H, s,
eCO2CH3), 6.50 (1H, q, J 7.0 Hz, eCH), 7.02 (1H, s, ]CHpyrrole), 7.17
(2H, d, J 7.5 Hz, HeAr), 7.22 (2H, d, J 7.5 Hz, HeAr), 7.30 (3H, t, J
7.5 Hz, HeAr), 7.34 (2H, dd, J 7.5 Hz, HeAr); dC (125 MHz, CDCl3):
21.1, 21.9, 39.5, 53.1, 53.5, 55.9, 122.1, 122.2, 124.1, 126.5, 127.3, 127.7,
128.7, 129.3, 130.6, 136.6, 141.7, 160.9, 167.3; HR-Mass (ESI) calcd for
C23H24NO4 [Mþ1]þ 378.1702, found 378.1701.
3
V¼917.99(3) A ,
r
¼1.427ꢁg/cm3, T¼200(2) K, qmax¼27.49ꢁ, radiation
ꢀ
ꢀ
Mo K
a
,
l
¼0.71073 A, 0.3
u
-scans with CCD area detector, covering
a whole sphere in reciprocal space, 9415 reflections measured, 4191
(I)), intensities were
unique (R(int)¼0.0758), 2818 observed (I>2
s
corrected for Lorentz and polarization effects, an empirical ab-
sorption correction was applied using SADABS1 based on the Laue
symmetry of the reciprocal space,
m
¼0.11 mmꢀ1
Tmin¼0.96,
,
Tmax¼0.99, structure solved by direct methods and refined against
F2 with a Full-matrix least-squares algorithm using the SHELXTL
(Version 2008/4) software package,2 264 parameters refined, hy-
drogen atoms were treated using appropriate riding models,
goodness of fit 1.00 for observed reflections, final residual values
R1(F)¼0.053, wR(F2)¼0.128 for observed reflections, residual elec-
3.1.13. 2-Ethyl 3-methyl1-allyl-4-phenyl-1H-pyrrole-2,3-
dicarboxylate (4m). Yellow oil (254 mg, 85%); Rf (25% EtOAC/hex-
ane) 0.55; nmax (neat): 1606 cmꢀ1, 1730, 2946, 3083; dH (500 MHz,
CDCl3): 3.82 (3H, s, eCO2CH3), 3.83 (3H, s, eCO2CH3), 4.92 (2H, d, J
5.5 Hz, eCH2N), 5.11 (1H, d, J 17.1 Hz, ]CH), 5.20 (1H, d, J 10.25 Hz,
]CH2), 6.0 (m, 1H, ]CH2), 6.93 (1H, s, ]CHpyrrole), 7.25 (1H, t, J
7.3 Hz, HeAr), 7.33 (2H, t, J 7.5 Hz, HeAr), 7.38 (2H, d, J 7.8 Hz,
HeAr); dC (125 MHz, CDCl3): 51.4, 51.8, 52.4, 117.7, 120.8, 122.1,
123.9, 125.3, 126.9, 127.3, 128.6, 133.3, 133.7, 160.6, 167.3; HR-Mass
(ESI) calcd for C19H22NO4 [Mþ1]þ 300.1230, found 300.1230.
ꢀꢀ3
tron density ꢀ0.28 to 0.27 e A . CCDC 808923 contains the sup-
plementary crystallographic data for this paper. These data can be
obtained free of charge from The Cambridge Crystallographic Data
Centre via www.ccdc.cam.ac.uk/data_request/cif.
3.1.8. Dimethyl 4-phenyl-1-(1-phenylethyl)-1H-pyrrole-2,3-
3.1.14. Diethyl 1-allyl-4-phenyl-1H-pyrrole-2,3-dicarboxylate
(4n). Yellow oil (284 mg, 87%); Rf (25% EtOAC/hexane) 0.51; nmax
(neat): 1602 cmꢀ1, 1713, 2976, 3079; dH (500 MHz, CDCl3): 1.27 (3H,
t, J 7.0 Hz, eCH3), 1.33 (3H, t, J 7.0 Hz, eCH3), 4.28 (4H, q, J 7.0 Hz, 2-
CH2), 4.92 (2H, d, J 5.5 Hz, eCH2N), 5.12 (1H, dd, J 18.1 Hz, ]CHa),
5.20 (1H, d, J 10.5 Hz, ]CHb), 5.99 (1H, m,), 6.92 (1H, s, ]CHpyr-
role), 7.25 (1H, t, J 8.5 Hz, HeAr), 7.34 (2H, t, J 7.5 Hz, HeAr), 7.40
(2H, d, J 7.5 Hz, HeAr); dC (125 MHz, CDCl3): 14.0, 14.1, 51.3, 60.7,
61.2, 117.7, 120.8, 122.4, 123.7, 125.1, 126.8, 127.4, 128.5, 133.5, 133.8,
160.2, 166.8; HR-Mass (ESI) calcd for C19H22NO4 [Mþ1]þ 328.1545,
found 328.1545.
dicarboxylate (4h). Yellow oil (309 mg, 82%); Rf (25% EtOAC/hex-
ane) 0.58; nmax (neat): 1711 cmꢀ1
; dH (500 MHz, CDCl3): 1.85 (3H, d,
J 7.0 Hz, eCH3), 3.80 (3H, s, eCO2CH3), 3.83 (3H, s, eCO2CH3), 6.50
(1H, q, J 7.0 Hz, eCH), 7.05 (1H, s, ]CHpyrrole), 7.21e7.30 (4H, m,
HeAr), 7.34 (4H, t, J 7.5 Hz, HeAr), 7.4 (2H, d, J 7.5 Hz, HeAr); dC
(125 MHz, CDCl3): 22.0, 52.2, 53.1, 56.0, 122.3, 126.4, 126.5, 126.9,
127.0, 127.4, 127.7, 128.5, 128.7, 128.8, 133.5, 141.6, 160.8, 167.3; HR-
Mass (ESI) calcd for C22H22NO4 [Mþ1]þ 364.1544, found 364.1544.
3.1.9. Dimethyl 4-(2-bromophenyl)-1-(1-phenylethyl)-1H-pyrrole-
2,3-dicarboxylate (4i). Yellow oil (396 mg, 87%); Rf (25% EtOAC/
hexane) 0.48; nmax (neat): 1715 cmꢀ1
;
dH (500 MHz, CDCl3): 1.84
3.1.15. 2-Ethyl 3-methyl 1,4-diphenyl-1H-pyrrole-2,3-dicarboxylate
(3H, d, J 7.0 Hz, eCH3), 3.68 (3H, s, eOCH3), 3.87 (3H, s, eOCH3), 6.31
(1H, q, J 7.0 Hz, eCHN), 7.02 (1H, s, ]CHpyrrole), 7.15 (1H, t, J 8.5 Hz,
HeAr), 7.22 (2H, d, J 7.5 Hz, HeAr), 7.25e7.37 (5H, m, HeAr), 7.61
(2H, d, J 7.5 Hz, HeAr); dC (125 MHz, CDCl3): 22.0, 51.8, 51.9, 56.2,
(4o). Yellow oil (251 mg, 75%); Rf (25% EtOAC/hexane) 0.48; nmax
(neat): 1605, 1701, 1725, 2984 cmꢀ1
; dH (500 MHz, CDCl3): 3.71 (3H,
s, eCO2CH3), 3.84 (3H, s, eCO2CH3), 7.0 (1H, s, ]CHpyrrole),
7.25e7.45 (m, 10H, HeAr); dC (125 MHz, CDCl3): 51.9, 52.3, 120.8,

5420
E. Ghabraie et al. / Tetrahedron 67 (2011) 5415e5420
4. (a) Kimura, T.; Kawara, A.; Nakao, A.; Ushiyama, S.; Shimozato, T.; Suzuki, K. PCt
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121.8, 125.9, 126.1, 127.1, 127.7, 128.5, 128.6, 128.9, 129.1, 133.1, 139.5,
160.4, 166.6; HR-Mass (ESI) calcd for C20H17NO4 [Mþ1]þ 336.1231,
found 336.1231.
3.1.16. 2-Ethyl 3-methyl 1-(4-methoxyphenyl)-4-phenyl-1H-pyrrole-
2,3-dicarboxylate (4p). Yellow oil (285 mg, 78%); Rf (25% EtOAC/
hexane) 0.41; nmax (neat): 1456, 1717, 2925, 2951 cmꢀ1
; dH
(500 MHz, CDCl3): 3.72 (3H, s, CO2CH3), 3.83 (3H, s, eCO2CH3), 3.82
(3H, s, eCO2CH3), 3.83 (3H, s, eCO2CH3), 6.95 (2H, d, J 8.5 Hz, HeAr),
6.97 (1H, s, ]CHpyrrole), 7.27 (2H, d, J 8.8 Hz, HeAr), 7.29 (1H, t, J
7.5 Hz, HeAr), 7.37 (2H, t, J 7.5 Hz, HeAr), 7.44 (2H, d, J 8.5 Hz,
HeAr); dC (125 MHz, CDCl3): 51.9, 52.3, 55.5, 114.0, 120.8, 124.6,
126.2, 127.0, 127.3, 127.4, 127.7, 128.5, 132.4, 133.3, 159.6, 160.4,
166.7; HR-Mass (ESI) calcd for C21H20NO5 [Mþ1]þ 366.1338, found
366.1338.
12. Cheng, L.; Lightner, D. A. Synthesis 1999, 1, 46.
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Acknowledgements
S.B. gratefully acknowledges Alexander von Humboldt founda-
tion for research fellowship. We are also grateful to Prof. R. Gleiter
for fruitful helpful discussions. We express our gratitude to Mr. M.
Jalilevand, managing director of Kimia Exir Company for chemical
donation and financial support.
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Patterson, J. M. Synthesis 1976, 281.
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Chem. 1999, 64, 1630.
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eimanifard, B. Helv. Chim. Acta 2009, 92, 932; (d) Khoshkholgh, M. J.; Lotfi, M.;
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Supplementary data
Supplementary data associated with this article can be found in
the online version at doi:10.1016/j.tet.2011.05.076.
References and notes
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