Bridging homogeneous and heterogeneous catalysis with CAN·SiO2 as a solid catalyst for four-component reactions for the synthesis of tetrasubstituted pyrroles

Article abstract of DOI:10.1039/c4nj01234h

An efficient and expeditious method has been developed for the synthesis of tetrasubstituted pyrroles via a four component, one-pot cyclocondensation reaction of amines, aldehydes, dialkyl acetylenedicarboxylates and nitroalkanes using silica supported ceric ammonium nitrate as a heterogeneous catalyst for the first time. Reusable silica supported ceric ammonium nitrate was found to be a highly efficient and renewable heterogeneous catalyst for the rapid and convenient synthesis of tetrasubstituted pyrrole derivatives. The advantageous features of this novel methodology are high atom-economy, operational simplicity, shorter reaction times, convergence, and facile automation.

Full text of DOI:10.1039/c4nj01234h

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Bridging homogeneous and heterogeneous
catalysis with CANÁSiO as a solid catalyst for
2
Cite this: New J. Chem., 2015,
four-component reactions for the synthesis
3
9, 396
of tetrasubstituted pyrroles†
Amol B. Atar, Jong Su Kim, Kwon Taek Lim and Yeon Tae Jeong*
An efficient and expeditious method has been developed for the synthesis of tetrasubstituted pyrroles via a
four component, one-pot cyclocondensation reaction of amines, aldehydes, dialkyl acetylenedicarboxylates
and nitroalkanes using silica supported ceric ammonium nitrate as a heterogeneous catalyst for the first
time. Reusable silica supported ceric ammonium nitrate was found to be a highly efficient and renewable
heterogeneous catalyst for the rapid and convenient synthesis of tetrasubstituted pyrrole derivatives. The
advantageous features of this novel methodology are high atom-economy, operational simplicity, shorter
reaction times, convergence, and facile automation.
Received (in Montpellier, France)
4th July 2014,
Accepted 16th October 2014
2
DOI: 10.1039/c4nj01234h
www.rsc.org/njc
In the midst of them, multicomponent processes have received
great attention from the chemical community because they
1
. Introduction
Polysubstituted pyrroles represent some of the most important address fundamental principles of synthetic efficiency and reac-
1
4
classes of heterocyclic molecules found in numerous natural tion processing. Multicomponent coupling reactions (MCRs)
1
and biologically active compounds. Polysubstituted pyrroles are known as powerful tools for the construction of novel and
have received considerable attention in the field of synthetic structurally complex molecules in a single pot ensuring high
organic chemistry due to their numerous applications in the atom economy, good overall yields and high selectivity, lower
2
pharmaceutical industry. Functionalized pyrroles have shown costs, shorter reaction times, minimizing waste, labor, energy,
3
15
interesting biological properties such as antibacterial, anti- and avoidance of expensive purification processes.
4
5
6
inflammatory, antioxidant, antitumor, antifungal and immune
suppressant activities. Highly functionalized pyrroles are subunits dialkyl acetylenedicarboxylates and nitroalkanes is reported to
of heme, chlorophyll, bile pigments, vitamin B12 and pyrrole give diversity oriented pyrroles by using iodine as a catalyst.
alkaloids isolated from the marine source. Furthermore, sub- But unfortunately, they used homogenous catalysts and are not
Recently, a four-component reaction of amines, aldehydes,
7
1
6
8
stituted pyrroles are widely used as synthetic building blocks, recyclable. The use of homogeneous catalysts has received little
9
pharmacophores, and various kinds of functional materials.
attention as alternatives in alleviating some of the limitations.
These compounds have many applications as chemosensors, for Thus, the search for an inexpensive, readily available, and
1
0
laser manufacture, and image diagnosis.
convenient catalyst is desirable. The use of heterogeneous
1
7
The importance of chemical and pharmacological properties catalysts has received considerable importance in organic
of pyrrole derivatives and the development of synthetic methods, synthesis because of their ease of handling, enhanced reaction
which enable a facile access to these heterocyclic compounds, rates, greater selectivity, simple work-up, and recoverability
are desirable. Recently, many efforts have been devoted to of catalysts. Among the various heterogeneous catalysts, parti-
develop novel and highly efficient synthetic protocols for the cularly, silica gel-supported ceric ammonium nitrate has
synthesis of functionalized pyrroles such as multicomponent the advantages of low cost, ease of preparation and catalyst
coupling, tandem reactions, transition-metal-catalyzed cycliza- recycling. It is evident from the previous literature that silica gel
tion, and catalytic C–H bond functionalization strategies have supported ceric ammonium nitrate has invoked enormous
been developed and drawn extensive and enduring attention.
1
8
1
1
1
2
1
3
interest as a green and a potential acid catalyst to construct
carbon–carbon and carbon–heteroatom bonds in various
1
9
organic transformations.
Department of Image Science and Engineering, Pukyong National University,
Busan 608-737, Republic of Korea. E-mail: ytjeong@pknu.ac.kr; Fax: +82 51 629 6408
Electronic supplementary information (ESI) available. See DOI: 10.1039/
c4nj01234h
As part of our ongoing research program for the develop-
ment of new environmentally benign methodology for the
synthesis of a useful precursor in the field of biology, industry,
†
396 | New J. Chem., 2015, 39, 396--402
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Scheme 1 Synthesis of fully substituted tetrasubstituted pyrrole functionalities catalyzed by CANÁSiO
2
.
2
0–23
and a key intermediate for the multistep synthesis,
we pyrroles, a test reaction was performed without catalysts using
decided to investigate the efficiency of a silica gel supported the model reaction under reflux conditions. It was found that
ceric ammonium nitrate catalyst for the synthesis of function- only a trace amount of product was obtained in the absence of a
alized pyrroles. The reaction is easy to perform and allows catalyst even after 24 h (Table 1, entry 1).
synthesizing various multi functionalized derivatives. These
In search of an effective, eco-friendly, and efficient reusable
reaction workup procedures are simple and we can isolate catalytic system for this reaction, the same test reaction was
products with high purity and yields. So herein, we wish to performed with different metal Lewis acid catalysts such as
report a tandem synthesis of tetrasubstituted pyrrole deriva- SiO
tives by using CANÁSiO as an expeditious reusable catalyst in SiO
an excellent yield (Scheme 1).
2
, BF
3
ÁSiO
2
, Cu(OTf)
, Zn(OTf)
, the reaction was tested with SiO
100 mg) only, and we observed a good yield as compared to the
catalyst free reaction (Table 1, entry 2). Among all screened
gave the best results in view of yield
2
ÁSiO
2
, FeCl
3
ÁSiO
2
, TiO
2
ÁSiO
2
, ZnCl
(Table 1).
2
Á
2
2
, CAN, CANÁSiO
2
2
ÁSiO
2
and P
2
O
5
ÁSiO
2
To study the role of SiO
2
2
(
2
. Results and discussion
catalysts CAN and CANÁSiO
To identify the suitable conditions for the four-component and reaction times (Table 1, entries 8 and 9). In contrast, BF
annulation process, a series of catalysts and solvents were Cu(OTf) , FeCl ÁSiO , TiO ÁSiO , ZnCl ÁSiO , Zn(OTf)
ÁSiO
screened (Table 1). Initially, in search of the best catalytic and P
ÁSiO
system for this one-pot synthesis, optimization of various (Table 1, entries 3–7, 10 and 11). The supported Lewis acid
reaction parameters like different metal Lewis acid catalysts, catalyst, FeCl , is effective, but it required more time for
ÁSiO
2
3
ÁSiO
2
,
2
2
3
2
2
2
2
2
2
ÁSiO
2
O
2 5
2
did not afford the desired product in good yields
3
2
temperature, and solvents was carried out (Table 1) with the the completion of the reaction as compared with a CANÁSiO
2
standard reaction of benzaldehyde, aniline, dimethyl acetylene- catalyst to slightly lower the yield (Table 1, entries 5, 9 and 12).
dicarboxylates, and nitromethane. In order to establish the real The reaction was also studied in various solvents such as tetra-
effectiveness of the catalyst for the synthesis of tetra substituted hydrofuran, dichloromethane, dichloroethane, and toluene; how-
ever, the yield of the desired product was decreased. So, in this
reaction nitromethane was used both as a solvent and as one of
the reactants as well.
a
Table 1 Optimization of the formation of tetrasubstituted pyrroles
Once we found CANÁSiO
2
as the best catalyst for this system,
the optimization of catalyst loading was done (Table 1,
entries 14–17). Consequently, the optimum 10 mol% loading
of CANÁSiO
2
provided the maximum yield in minimum time
Table 1, entry 9), but while loading a high amount of catalyst,
(
b
the reaction proceeded quite slowly with a lower yield (Table 2,
entries 16 and 17), on the other hand, a decrease in the yield
was observed by lowering the amount of catalyst (Table 1, entries
14 and 15). So, 10 mol% of the catalyst were found to be the
optimal quantity and sufficient to push the reaction forward.
To explore the scope of this novel methodology, reactions of
several of amines, aldehydes, dialkyl acetylenedicarboxylates
Entry
Catalyst (10 mol%)
—
Time (h)
Yield (%)
1
2
3
4
5
6
7
8
9
24
12
10
12
8
12
8
4
4
9
12
24
24
4
4
6
Traces
24
SiO
BF
Cu(OTf)
FeCl
ÁSiO
TiO
ÁSiO
ÁSiO
2
3
ÁSiO
2
48
51
75
52
60
91
93
65
55
85
90
85
88
90
89
2
ÁSiO
2
3
2
2
2
ZnCl
CAN
2
2
and nitromethane in the presence of 10 mol% of CANÁSiO
2
were
CANÁSiO
Zn(OTf)
ÁSiO
2
conducted. The results are summarized in Table 2. Thus,
we selected the optimized reaction condition to examine the
universality of this catalyst application with different electron
rich and deficient substrates. It was gratifying to observe that most
of the tested substrates exhibited satisfactory reactivity profiles, in
all cases leading to a heterocyclization sequence that readily
afforded the target structures (Table 2). But, with an aliphatic
aldehyde only a trace amount of product was detected (Table 2,
entry 29). On the other hand, in the case of amines, both aromatic
and aliphatic substrates underwent the conversion smoothly.
10
11
12
13
14
15
16
17
2
ÁSiO
2
P
FeCl
2
O
5
2
3
ÁSiO
2
CANÁSiO
CANÁSiO
CANÁSiO
CANÁSiO
CANÁSiO
2
2
2
2
2
(5 mol%)
(7 mol%)
(15 mol%)
(20 mol%)
5
a
All reactions were carried out using benzaldehyde (1 mmol), aniline
1 mmol), dimethyl acetylenedicarboxylates (1 mmol) and nitromethane
1 mL) under reflux conditions. Yields obtained after column chromato-
(
(
b
graphy.
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Table 2 Synthesis of tetrasubstituted pyrroles by four-component coupling
Table 3 Recycling and reuse of CANÁSiO
2
a
2
reactions using CANÁSiO as a catalyst
a
Entry
Reaction cycle
Yield (%)
1
2
3
4
First (fresh run)
Second cycle
Third cycle
93
93
91
90
Fourth cycle
b
Entry
compound)
Time Yield
a
Isolated yield.
(
R
1
R
2
R
3
(h)
(%)
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
Ph
2-CH
4-OCH
3-CH
4-CH
3-OCH
4-CH
4-OCH
PhCH
2-OCH
4-ClC
4-BrC
4-OCH
3,5-OCH
3,4-CH
PhCH
PhCH
4-OCH
3,5-CH
2,5-CH
3,4-CH
Ph
PhCH
3,4-OCH
PhCH
5-Amino indane Ph
4-OCH 2,3-FC
2,4,6-CH
Ph
Ph
Ph
2-CH
Ph
Ph
Ph
4-OHC
Ph
4-OEtC
Ph
Ph
Ph
4-FC
Ph
Ph
4-BrC
3-FC
3,4-FC
Ph
Ph
Ph
Me
Et
Et
Et
Et
Et
Me
Et
Me
Et
Et
4
5
5
4
5
6
5
4
4
6
5
4
5
6
5
4
5
4
5
6
4
6
4
4
4
6
6
6
93
92
91
93
90
89
88
90
96
85
87
88
92
86
90
94
95
93
89
86
92
62
95
92
90
88
85
82
The reusability of the CANÁSiO
2
catalyst was also examined.
3
C
3
6
H
4
6
C H
4
3
C
6
H
4
The catalyst was reused four times and the results show that
silica supported ceric ammonium nitrate can be reused as such
without a significant loss in yield (Table 3). The recyclability of
the catalyst was checked with the model reaction (Table 3,
entries 1–4). Accordingly, after the first fresh run with a 93%
yield, the catalyst was removed by filtration. The recovered
catalyst was dried under vacuum at 120 1C for 12 h and tested
up to three more reaction cycles. Recycling and reuse of the
catalyst showed a minimal decrease in yields. The product was
obtained in 93%, 93%, 91%, and 90% yields after successive
cycles (Table 3, entries 1–4), thus proving the catalyst reusability.
The catalyst showed excellent recyclability in all these reactions
(Table 3), as the reaction times and yields remained almost the
same without having a loss of catalytic activity.
3
C
C
6
H
H
4
3
6
4
3
6
C H
4
4
4
3
C
6
H
4
6
H
4
3
C
6
6
H
2
6
H
4
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
C
H
6
H
4
6
H
4
Et
Me
Et
3
C
3
6
H
C
4
H
6
H
4
6
H
3
3
C
6
3
Et
2
6
H
4
Me
Me
Me
Et
Et
Me
2
6
H
4
3
6
C H
4
6 3
H
3
3
3
C
6
C
6
C
6
H
H
H
3
3
3
The reported as well as synthesized novel compounds were
further characterized by their spectral properties ( H, C NMR,
and HRMS).
Thiophene Me
4-CH
Ph
3-FC
1
13
2
3
C
6
H
4
Me
Et
Et
Me
Me
Et
3
C
6
H
3
2
6
H
4
3
C
3
6
H
C
4
6
H
3
6
H
2
Ph
CH
Ph
3. Conclusion
3
CH
2
Me 24
Traces
75
89
H
2
CQCH–CH
PhCH
5-Amino indane Ph
2
Et
Et
Et
4
5
4
In summary, an efficient, expeditious, operationally simple,
economical, and environmentally friendly method has been
developed for the synthesis of tetra-substituted pyrroles via a
four component; one-pot reaction of amines, aldehydes, dialkyl
acetylenedicarboxylates, and nitromethane using silica sup-
ported ceric ammonium nitrate as a heterogeneous catalyst.
The main advantage of this present methodology is the simple
2
4-BrC
6
H
4
84
a
All reactions were carried out using amines (1 mmol), aldehydes
(
(
1 mmol), dialkyl acetylenedicarboxylates (1 mmol) and nitromethane
1 mL) under reflux conditions. Isolated yield.
b
A possible mechanism of this one-pot reaction is expected on work-up, easy recovery of catalysts, no need for anhydrous condi-
1
7
the basis of the reported literature. A possible mechanism for tions, and no base or any additional activator required. To the best
the tetrasubstituted pyrrole ring formation of four-component of our knowledge this is the first report for the synthesis of tetra-
coupling reactions using CANÁSiO
2
as a catalyst is outlined in substituted pyrroles by using silica supported ceric ammonium
nitrate as a heterogeneous catalyst. Shorter reaction times,
Scheme 2.
Scheme 2 Plausible mechanism for the formation of substituted pyrrole derivatives.
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excellent yields, and more importantly, the recyclability without
losing catalytic activity make this protocol good and attractive. pyrrole-2,3-dicarboxylate. Yellow sticky liquid;
4.3.3. Diethyl 1-(4-methoxyphenyl)-4-(2-methyphenyl)-1H-
1
H NMR
(
400 MHz, CDCl ) d (ppm) 7.27–7.22 (m, 5H), 7.09 (d, J =
3
4
Hz, 1H), 6.95–6.92 (m, 3H), 4.35–4.29 (m, 2H), 4.19–4.13
(
(
m, 2H), 3.83 (s, 3H), 2.35 (s, 3H), 1.30 (d, J = 12 Hz, 3H), 1.17
d, J = 12 Hz, 3H); C NMR (CDCl , 100 MHz) d (ppm) 166.41,
3
4
. Experimental
13
4.1 Material and methods
159.89, 159.48, 138.00, 133.19, 132.55, 128.43, 127.78, 127.45,
1
5
26.10, 124.77, 124.48, 123.17, 121.95, 113.90, 61.25, 60.70,
5.50, 21.45, 14.09, 13.95; HRMS m/z calcd for C24 25NO
5
Chemicals were purchased from Aldrich and Alfa Aesar
chemical companies and used as it is. The NMR spectra were
recorded in CDCl3 on a Jeol JNMECP 400 NMR instrument
using TMS as an internal standard. The HRMS was recorded on
a Jeol JMS-700 mass spectrometer.
H
+
[M ] 407.1733, found 407.1736.
4
.3.4. Diethyl 1-(3-methylphenyl)-4-phenyl-1H-pyrrole-2,3-
1
dicarboxylate. Yellow sticky liquid; H NMR (400 MHz, CDCl )
d (ppm) 7.44 (d, J = 8 Hz, 2H), 7.29 (t, J = 8 Hz, 2H), 7.22 (t, J =
3
1
2 Hz, 2H), 7.15 (d, J = 8 Hz, 1H), 7.09 (t, J = 12 Hz, 2H), 6.90
4
.2 General procedure for the synthesis of a silica supported
(
(
s, 1H), 4.29–4.26 (m, 2H), 4.14–4.11 (m, 2H), 2.32 (s, 3H), 1.24
t, J = 12 Hz, 3H), 1.11 (t, J = 12 Hz, 3H); C NMR (CDCl , 100
3
ceric ammonium nitrate catalyst
13
A silica supported ceric ammonium nitrate catalyst was MHz) d (ppm) 166.01, 159.91, 139.42, 138.77, 133.29, 129.05,
2
4
prepared by adopting the literature procedure. Neutral silica 128.58, 128.38, 127.74, 126.95, 126.60, 125.50, 124.66, 123.10,
gel (9.01 g, Merck Kieselgel 60, particle size 0.063–0.200 mm, 121.71, 61.09, 60.70, 21.14, 13.99, 13.82; HRMS m/z calcd for
+
7
0–230 mesh) was mixed with a solution of CAN (1.02 g) in C H NO [M ] 377.1627, found 377.1629.
2
3
23
4
water (2.0 mL). Evaporation of water under reduced pressure
gave a dry yellowish powder, which contained 10% (by weight) dicarboxylate. Yellow sticky liquid; H NMR (400 MHz, CDCl
4.3.5. Diethyl 1-(4-methylphenyl)-4-phenyl-1H-pyrrole-2,3-
1
3
)
of CAN. According to Hwu et al., this reagent was found active d (ppm) 7.43 (t, J = 12 Hz, 2H), 7.28–7.19 (m, 3H), 7.12 (t, J =
2
4
for at least six months by storing in a well-capped bottle.
.3 General procedure for the synthesis of fully substituted (s, 3H), 1.23 (t, J = 12 Hz, 3H), 1.11 (t, J = 12 Hz, 3H); C NMR
pyrrole functionalities. To a mixture of amines (1 mmol), (CDCl , 100 MHz) d (ppm) 166.03, 159.87, 138.17, 136.99,
8 Hz, 4H), 6.87 (s, 1H), 4.2–4.25 (m, 2H), 4.13–4.10 (m, 2H), 2.29
1
3
4
3
aldehydes (1 mmol), dialkyl acetylenedicarboxylates (1 mmol) 133.33, 129.36, 128.39, 127.71, 126.94, 125.80, 125.63, 124.56,
and nitromethane (1 mL) was added 10 mol% CANÁSiO and 123.58, 121.76, 61.06, 60.67, 20.97, 14.00, 13.84; HRMS m/z
2
+
the reaction mixture was kept for refluxing in a heated oil-bath calcd for C H NO [M ] 377.1627, found 377.1629.
2
3
23
4
with constant stirring. After completion of the reaction as
monitored by TLC, the reaction mixture was brought to room dicarboxylate. Yellow sticky liquid; H NMR (400 MHz, CDCl
4.3.6. Diethyl 1-(3-methoxyphenyl)-4-phenyl-1H-pyrrole-2,3-
1
3
)
temperature and the excess nitroalkane was removed using d (ppm) 7.46–7.44 (m, 2H), 7.37–7.32 (m, 2H), 7.30–7.24 (m, 2H),
a rotary evaporator. Then, the crude residue was dissolved in 6.98 (s, 1H), 9.96–6.92 (m, 2H), 6.89 (t, J = 12 Hz, 1H), 4.33–4.28
1
0 mL of dichloromethane and the solid particle was removed (m, 2H), 4.20–4.14 (m, 2H), 3.80 (s, 3H), 1.27 (t, J = 12 Hz, 3H),
1
3
by filtration. The precipitate was further washed with 2 mL of 1.16 (t, J = 12 Hz, 3H); C NMR (CDCl , 100 MHz) d (ppm)
3
dichloromethane. The filtrate was washed with water and dried 166.09, 159.93, 159.85, 140.58, 133.25, 129.55, 128.45, 127.81,
over anhydrous sodium sulfate. The organic extract was con- 127.06, 125.51, 124.79, 123.64, 121.76, 118.38, 114.19, 112.03,
centrated and the crude residue was finally purified through 61.25, 60.86, 55.44, 14.03, 13.89; HRMS m/z calcd for C23
a silica gel column chromatography. The final product was [M ] 393.4324, found 393.4321.
H
23NO
5
+
obtained by eluting with an ethyl acetate and hexane mixture.
4.3.7. Dimethyl
1-(4-methylphenyl)-4-(4-hydroxyphenyl)-
1
4
.3.1. Dimethyl 4-(phenyl)-1-phenyl-1H-pyrrole-2,3-dicarboxyl- 1H-pyrrole-2,3-dicarboxylate. Brown sticky liquid; H NMR
1
3 3
ate. Brown sticky liquid; H NMR (400 MHz, CDCl ) d (ppm) (400 MHz, CDCl ) d (ppm) 7.24–7.22 (m, 3H), 7.20–7.15
7
.48–7.32 (m, 5H), 7.26–7.15 (m, 5H), 7.02 (s, 1H), 3.82 (s, 3H), (m, 4H), 6.87 (s, 1H), 6.76 (d, J = 8 Hz, 2H), 3.81 (s, 3H), 3.67
13
13
3.74 (s, 3H); C NMR (CDCl , 100 MHz) d (ppm) 166.52, 160.12, (s, 3H), 2.34 (s, 3H); C NMR (CDCl , 100 MHz) d (ppm) 167.48,
3
3
1
38.12, 133.20, 129.32, 128.56, 127.66, 127.09, 126.58, 125.45, 160.74, 155.72, 138.41, 136.80, 129.48, 128.90, 125.80, 125.71,
+
1
3
21.23, 120.73, 55.23, 53.26; HRMS m/z calcd for C20
35.1158, found 335.1153.
.3.2. Diethyl 1-(2-methylphenyl)-4-phenyl-1H-pyrrole-2,3-
H
17NO
4
[M ] 124.84, 124.78, 122.93, 121.24, 115.62, 52.50, 51.99, 21.05;
+
HRMS m/z calcd for C21
H19NO
5
[M ] 365.1263, found 365.1264.
4
4.3.8. Diethyl 1-(4-methoxyphenyl)-4-phenyl-1H-pyrrole-2,3-
dicarboxylate. Yellow sticky liquid; H NMR (400 MHz, CDCl )
3
1
1
dicarboxylate. Yellow sticky liquid; H NMR (400 MHz, CDCl
3
)
d (ppm) 7.47–7.45 (m, 2H), 7.36–7.32 (m, 3H), 7.30–7.20 d (ppm) 7.46–7.43 (m, 2H), 7.35 (t, J = 12 Hz, 2H), 7.29–7.24
(
2
m, 4H), 6.88 (s, 1H), 4.34–4.32 (m, 2H), 4.11–4.08 (m, 2H), (m, 3H), 6.96–6.92 (m, 3H), 4.34–4.28 (m, 2H), 4.19–4.14 (m, 2H),
1
3
13
.11 (s, 3H), 1.29 (t, J = 12 Hz, 3H), 1.09 (t, J = 12 Hz, 3H);
C
3.83 (s, 3H), 1.28 (t, J = 12 Hz, 3H), 1.17 (t, J = 12 Hz, 3H);
C
NMR (CDCl , 100 MHz) d (ppm) 166.47, 159.52, 139.11, 135.46, NMR (CDCl , 100 MHz) d (ppm) 166.31, 159.92, 159.49, 133.33,
3
3
133.31, 130.42, 128.91, 128.52, 127.58, 127.35, 126.99, 126.30, 132.49, 128.47, 127.74, 127.42, 127.00, 126.04, 124.46, 123.41,
1
25.35, 124.60, 123.29, 121.85, 61.32, 60.55, 17.36, 14.06, 13.80; 121.77, 61.26, 60.74, 55.50, 14.05, 13.95; HRMS m/z calcd for
+
+
HRMS m/z calcd for C21
H19NO
4
[M ] 349.1314, found 349.1315.
23 5
C H23NO [M ] 393.4324, found 393.4321.
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Paper
4
.3.9. Dimethyl 1-(benzyl)-4-(4-ethoxyphenyl)-1H-pyrrole-
4.3.15. Diethyl 1-(3,4-dimethylphenyl)-4-phenyl-1H-pyrrole-
1
1
2
,3-dicarboxylate. Brown sticky liquid; H NMR (400 MHz, 2,3-dicarboxylate. Yellow sticky liquid; H NMR (400 MHz,
CDCl ) d (ppm) 7.30–7.22 (m, 5H), 7.14 (d, J = 8 Hz, 2H), 6.85 CDCl ) d (ppm) 7.44 (d, J = 8 Hz, 2H), 7.28 (t, J = 12 Hz, 2H),
3
3
(
d, J = 12 Hz, 2H), 6.83 (s, 1H), 5.46 (s, 2H), 4.01–3.96 (m, 2H), 7.21–7.17 (m, 1H), 7.10–7.05 (m, 2H), 7.00 (d, J = 8 Hz, 1H), 6.89
1
3
3
1
1
1
.79 (s, 3H), 3.75 (s, 3H), 1.37 (t, J = 12 Hz, 3H); C NMR (CDCl3, (s, 1H), 4.28–4.26 (m, 2H), 4.16–4.11 (m, 2H), 2.21 (s, 6H), 1.23
1
3
3
00 MHz) d (ppm) 167.35, 160.64, 158.12, 137.10, 128.74, (t, J = 12 Hz, 3H), 1.15 (t, J = 12 Hz, 3H); C NMR (CDCl ,
28.53, 127.79, 127.17, 125.62, 125.35, 123.82, 122.07, 120.90, 100 MHz) d (ppm) 166.04, 159.98, 137.21, 137.16, 136.83, 133.39,
15.35, 114.59, 63.39, 52.31, 51.71, 14.82; HRMS m/z calcd for 129.83, 128.37, 127.75, 126.94, 125.60, 124.55, 123.26, 121.50,
+
C
23
H
4
23NO
5
[M ] 393.4324, found 393.4323.
61.03, 60.68, 19.65, 19.33, 14.01, 13.87; HRMS m/z calcd for
+
.3.10. Diethyl 1-(2-methoxyphenyl)-4-phenyl-1H-pyrrole-
,3-dicarboxylate. Yellow sticky liquid; H NMR (400 MHz,
C
24
H
25NO
4
[M ] 391.4596, found 391.4595.
1
2
4.3.16. Dimethyl 1-(benzyl)-4-(4-bromophenyl)-1H-pyrrole-
1
CDCl ) d (ppm) 7.43 (d, J = 8 Hz, 2H), 7.32–7.27 (m, 3H), 2,3-dicarboxylate. Yellow sticky liquid; H NMR (400 MHz,
3
7
.21–7.18 (m, 2H), 6.95–6.91 (m, 2H), 6.83 (s, 1H), 4.29–4.26 CDCl ) d (ppm) 7.40–7.37 (m, 2H), 7.27–7.19 (m, 5H), 7.11
3
(
m, 2H), 4.10–4.06 (m, 2H), 3.64 (s, 3H), 1.24 (t, J = 12 Hz, 3H), (d, J = 8 Hz, 2H), 6.88 (s, 1H), 5.40 (s, 2H), 3.77 (s, 3H), 3.71
.07 (t, J = 12 Hz, 3H); C NMR (CDCl , 100 MHz) d (ppm) (s, 3H); C NMR (CDCl , 100 MHz) d (ppm) 166.82, 160.41,
3 3
66.36, 159.64, 154.42, 133.46, 129.71, 128.79, 128.40, 127.57, 136.84, 132.21, 131.56, 128.92, 128.70, 127.80, 127.05, 125.57,
1
3
13
1
1
1
6
3
26.81, 125.56, 124.27, 124.00, 121.51, 120.33, 111.56, 61.10, 122.68, 121.83, 121.52, 120.80, 52.27, 51.74; HRMS m/z calcd for
+
+
0.34, 55.48, 14.00, 13.83; HRMS m/z calcd for C23
H23NO
5
[M ]
C
21
H
18BrNO
4
[M ] 427.0419, found 427.0416.
93.4324, found 393.4321.
4.3.17. Dimethyl 1-(benzyl)-4-(3-fluorophenyl)-1H-pyrrole-
1
4.3.11. Diethyl 1-(4-chlorophenyl)-4-phenyl-1H-pyrrole-2,3- 2,3-dicarboxylate. Brown sticky liquid; H NMR (400 MHz,
1
dicarboxylate. Yellow sticky liquid; H NMR (400 MHz, CDCl ) d CDCl ) d (ppm) 7.32–7.22 (m, 5H), 7.16–7.12 (m, 3H), 7.09–
3
3
(
(
(
ppm) 7.45–7.40 (m, 4H), 7.35 (t, J = 12 Hz, 2H), 7.29–7.24 7.06 (m, 1H), 6.93 (s, 1H), 5.47 (s, 2H), 3.81 (s, 3H), 3.76 (s, 3H);
1
3
m, 3H), 6.95 (s, 1H), 4.34–4.28 (m, 2H), 4.20–4.14 (m, 2H), 1.28
C NMR (CDCl
3
, 100 MHz) d (ppm) 166.96, 164.11, 161.67,
1
3
t, J = 12 Hz, 3H), 1.18 (t, J = 12 Hz, 3H); C NMR (CDCl
3
, 100 160.53, 136.82, 135.51, 130.12, 130.04, 128.82, 127.93, 127.22,
MHz) d (ppm) 166.11, 159.67, 138.07, 134.37, 132.97, 129.02, 125.77, 122.99, 122.76, 122.13, 121.46, 114.29, 114.07, 113.84,
+
1
1
28.54, 127.66, 127.61, 127.19, 125.70, 125.70, 124.94, 122.99, 113.63, 52.43, 51.84; HRMS m/z calcd for C21
H
18FNO
4
[M ]
22.66, 61.38, 60.91, 14.03, 13.91; HRMS m/z calcd for 367.3703, found 367.3705.
+
C H ClNO [M ] 397.8515, found 397.8519.
4.3.18. Dimethyl 1-(4-methoxyphenyl)-4-(3,4-difluorophenyl)-
2
2
20
4
1
4
.3.12. Diethyl 1-(4-bromophenyl)-4-phenyl-1H-pyrrole-2,3- 1H-pyrrole-2,3-dicarboxylate. Brown sticky liquid;
H
NMR
1
dicarboxylate. Yellow sticky liquid; H NMR (400 MHz, CDCl
3 3
) d (400 MHz, CDCl ) d (ppm) 8.06 (d, J = 8 Hz, 1H), 7.56–7.47
(
1
ppm) 7.48 (d, J = 8 Hz, 2H), 7.41 (d, J = 8 Hz, 2H), 7.29 (t, J = (m, 3H), 7.37–7.32 (m, 2H), 7.27–7.21 (m, 2H), 4.03 (s, 3H), 3.95
13
3
2 Hz, 2H), 7.22 (d, J = 8 Hz, 1H), 7.13 (d, J = 12 Hz, 2H), 6.90 (s, 3H), 3.76 (s, 3H); C NMR (CDCl , 100 MHz) d (ppm) 167.99,
(
3
1
s, 1H), 4.29–4.26 (m, 2H), 4.14–4.10 (m, 2H), 1.25 (t, J = 12 Hz, 166.47, 159.52, 151.47, 144.69, 137.10, 131.45, 124.89, 124.69,
1
3
H), 1.14 (t, J = 12 Hz, 3H); C NMR (CDCl
3
, 100 MHz) d (ppm) 123.69, 117.96, 117.76, 117.36, 117.19, 102.69, 55.72, 53.22, 52.90;
+
65.92, 159.52, 138.44, 132.88, 131.87, 128.48, 127.80, 127.54, HRMS m/z calcd for C H F NO [M ] 401.3601, found 401.3603.
21
17
2
5
1
27.10, 125.56, 124.82, 122.93, 122.63, 122.12, 61.25, 60.82,
4.3.19. Diethyl 1-(3,5-dimethylphenyl)-4-phenyl-1H-pyrrole-
+
1
13.98, 13.84; HRMS m/z calcd for C H BrNO [M ] 442.3025, 2,3-dicarboxylate. Yellow sticky liquid; H NMR (400 MHz, CDCl )
2
2
20
4
3
found 442.3028.
d (ppm) 7.43 (d, J = 8 Hz, 2H), 7.27 (t, J = 12 Hz, 2H), 7.18 (t, J =
4
.3.13. Dimethyl 1-(4-methoxyphenyl)-4-(4-fluorophenyl)- 12 Hz, 1H), 6.97 (s, 1H), 6.85 (d, J = 8 Hz, 3H), 4.28–4.23 (m, 2H),
1
1
H-pyrrole-2,3-dicarboxylate. Brown sticky liquid; H NMR 4.15–4.10 (m, 2H), 2.26 (s, 6H), 1.22 (t, J = 12 Hz, 3H), 1.17 (t, J =
400 MHz, CDCl ) d (ppm) 8.05 (d, J = 8 Hz, 1H), 7.46–7.61 12 Hz, 3H); C NMR (CDCl , 100 MHz) d (ppm) 165.92, 160.01,
3 3
m, 2H), 7.47–7.44 (m, 1H), 7.36 (d, J = 4 Hz, 1H), 7.17–7.02 139.36, 138.52, 133.40, 129.91, 128.36, 127.80, 126.91, 125.37,
m, 3H), 6.95–6.91 (m, 1H), 4.02 (s, 3H), 3.93 (m, 3H), 3.72 124.65, 123.68, 121.45, 60.99, 60.68, 21.03, 13.99, 13.84; HRMS
13
(
(
(
13
+
(
s, 3H); C NMR (CDCl , 100 MHz) d (ppm) 168.25, 166.59, 159.26, m/z calcd for C H NO [M ] 391.4596, found 391.4597.
3
24 25
4
1
52.73, 144.71, 136.93, 131.40, 130.36, 130.27, 127.22, 124.89,
4.3.20. Diethyl 1-(2,5-dimethylphenyl)-4-phenyl-1H-pyrrole-
1
3
124.62, 123.45, 115.59, 115.36, 114.03, 55.66, 53.17, 52.78; HRMS 2,3-dicarboxylate. Yellow sticky liquid; H NMR (400 MHz, CDCl )
+
m/z calcd for C21
H
18FNO
5
[M ] 383.1669, found 383.1167.
d (ppm) 7.44 (d, J = 8 Hz, 2H), 7.27 (t, J = 12 Hz, 2H), 7.17 (t, J =
4
.3.14. Diethyl 1-(3,5-dimethoxyphenyl)-4-phenyl-1H-pyrrole- 12 Hz, 1H), 7.08 (s, 2H), 6.96 (s, 1H), 6.77 (s, 1H), 4.30–4.25
1
2
,3-dicarboxylate. Yellow sticky liquid; H NMR (400 MHz, CDCl
d (ppm) 7.44 (d, J = 8 Hz, 2H), 7.33 (t, J = 12 Hz, 2H), 7.28–7.23 12 Hz, 3H), 1.04 (t, J = 12 Hz, 3H); C NMR (CDCl
m, 1H), 6.97 (s, 1H), 6.50 (s, 3H), 4.32–4.27 (m, 2H), 4.21–4.16 (ppm) 166.26, 159.43, 138.88, 135.94, 133.37, 132.09, 130.47,
3
)
(m, 2H), 4.08–4.03 (m, 2H), 2.26 (s, 3H), 2.00 (s, 3H), 1.23 (t, J =
13
3
, 100 MHz) d
(
(
m, 2H), 3.75 (s, 6H), 1.26 (t, J = 12 Hz, 3H), 1.18 (t, J = 12 Hz, 3H); 130.17, 129.56, 128.45, 127.82, 127.53, 126.89, 125.30, 124.46,
1
3
C NMR (CDCl , 100 MHz) d (ppm) 165.94, 160.74, 159.99, 123.53, 121.71, 61.09, 60.41, 20.59, 16.75, 14.00, 13.75; HRMS
3
+
1
4
41.05, 133.26, 128.42, 127.86, 127.05, 125.29, 124.82, 123.91, m/z calcd for C24H25NO [M ] 391.1718, found 391.1786.
1
21.45, 104.60, 100.46, 61.19, 60.91, 55.49, 14.02, 13.92; HRMS
4.3.21. Dimethyl 1-(3,4-dimethylphenyl)-4-phenyl-1H-pyrrole-
2,3-dicarboxylate. Brown sticky liquid; H NMR (400 MHz, CDCl )
3
+
1
m/z calcd for C24
H
25NO
6
[M ] 423.4584, found 423.4582.
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+
17 2 5
d (ppm) 7.41 (d, J = 8 Hz, 2H), 7.29 (t, J = 8 Hz, 2H), 7.22–7.19 HRMS m/z calcd for C21H F NO [M ] 401.3602, found
(
6
m, 1H), 7.11 (d, J = 8 Hz, 1H), 7.06 (s, 1H), 7.00 (d, J = 8 Hz, 1H), 401.3605.
13
.90 (s, 1H), 3.78 (s, 3H), 3.66 (s, 3H), 2.23 (s, 6H); C NMR
4.3.28. Diethyl 1-(2,4,6-trimethylphenyl)-4-phenyl-1H-pyrrole-
1
(CDCl , 100 MHz) d (ppm) 166.54, 160.45, 137.29, 137.06, 136.96, 2,3-dicarboxylate. Yellow sticky liquid; H NMR (400 MHz, CDCl )
3
3
133.24, 129.88, 128.46, 127.65, 126.99, 126.80, 125.85, 124.62, d (ppm) 7.45 (d, J = 8 Hz, 2H), 7.33 (t, J = 12 Hz, 2H), 7.25 (d, J =
1
23.45, 123.19, 121.22, 52.12, 51.78, 19.69, 19.36; HRMS m/z calcd 8 Hz, 1H), 6.92 (s, 2H), 6.76 (s, 1H), 4.34–4.28 (m, 2H), 4.13–4.08
+
for C24
H
25NO
4
[M ] 391.4596, found 391.4598.
(m, 2H), 2.30 (s, 3H), 2.00 (s, 6H), 1.27 (t, J = 12 Hz, 3H), 1.10
13
4
.3.22. Dimethyl 1-(phenyl)-4-(thiophene)-1H-pyrrole-2,3- (t, J = 12 Hz, 3H); C NMR (CDCl
3
, 100 MHz) d (ppm) 166.37,
1
dicarboxylate. Brown sticky liquid; H NMR (400 MHz, CDCl
3
)
159.60, 138.31, 135.91, 135.25, 134.63, 133.47, 129.49, 128.58,
d (ppm) 7.42–7.32 (m, 4H), 7.26–7.15 (m, 4H), 6.99 (s, 1H), 3.75 128.43, 127.64, 126.88, 125.03, 124.52, 123.20, 121.30, 61.16,
1
3
(
1
1
s, 3H), 3.67 (s, 3H); C NMR (CDCl , 100 MHz) d (ppm) 165.42, 60.50, 20.89, 17.41, 14.04, 13.79; HRMS m/z calcd for C H NO
3
2
5
2
7
4
+
61.34, 139.54, 136.21, 129.57, 129.19, 128.71, 127.93, 126.44, [M ] 405.4862, found 405.4865.
25.86, 124.56, 124.21, 52.89, 52.21; HRMS m/z calcd for 4.3.29. Dimethyl 1-allyl-4-phenyl-1H-pyrrole-2,3-dicarboxylate.
+
1
C
18
H15NO
4
S [M ] 341.3810, found 341.3812.
3
Brown sticky liquid; H NMR (400 MHz, CDCl ) d (ppm) 7.43 (d, J =
4
.3.23. Dimethyl 1-(benzyl)-4-(4-methylphenyl)-1H-pyrrole- 8 Hz, 2H), 7.25 (t, J = 12 Hz, 2H), 7.20 (d, J = 8Hz, 1H), 6.91 (s, 1H),
1
2
,3-dicarboxylate. Yellow sticky liquid; H NMR (400 MHz, 6.02 (m, 1H), 5.22 (d, J = 10 Hz, 1H), 5.13 (d, J = 16 Hz, 1H), 5.01
CDCl ) d (ppm) 7.27–7.17 (m, 5H), 7.14–7.09 (m, 4H), 6.86 (d, J = 5 Hz, 2H), 3.82 (s, 3H), 3.76 (s, 3H); C NMR (CDCl ,
3 3
s, 1H), 5.41 (s, 2H), 3.76 (s, 3H), 3.70 (s, 3H), 2.28 (s, 3H);
13
1
3
(
C
100 MHz) d (ppm) 166.32, 160.51, 133.74, 126.56, 127.21, 126.85,
NMR (CDCl , 100 MHz) d (ppm) 167.30, 160.56, 137.11, 136.55, 125.32, 123.87, 122.12, 120.85, 118.75, 53.21, 51.36, 51.01; HRMS
3
+
1
1
C
30.33, 129.28, 128.68, 127.73, 127.16, 127.08, 125.60, 123.90, m/z calcd for C H NO [M ] 299.3212, found 299.3215.
17 17 4
22.19, 120.93, 52.24, 51.64, 21.03; HRMS m/z calcd for
4.3.30. Diethyl 1-(benzyl)-4-(4-bromophenyl)-1H-pyrrole-
2,3-dicarboxylate. Yellow sticky liquid; H NMR (400 MHz,
+
1
22
H21NO
4
[M ] 363.4064, found 363.4066.
4
.3.24. Diethyl 1-(3,4-dimethoxyphenyl)-4-phenyl-1H-pyrrole- CDCl
3
) d (ppm) 7.50 (d, J = 8 Hz, 2H), 7.41 (d, J = 8 Hz, 1H),
1
2
,3-dicarboxylate. Yellow sticky liquid; H NMR (400 MHz, CDCl
3
)
7.34 (m, 4H), 7.15 (d, J = 4 Hz, 2H), 6.90 (s, 1H), 5.47 (s, 2H),
1
3
d (ppm) 7.45 (d, J = 8 Hz, 2H), 7.34 (t, J = 12 Hz, 2H), 7.27 (t, J = 4.30–4.21 (m, 4H), 1.30–1.22 (m, 6H); C NMR (CDCl
3
, 100 MHz)
Hz, 1H), 6.97 (s, 1H), 6.92–6.86 (m, 3H),4.33–4.28 (m, 2H), 4.19– d (ppm) 166.44, 160.11, 137.62, 137.45, 136.91, 132.53, 131.50,
.14 (m, 2H), 3.88 (s, 3H), 3.84 (s, 3H), 1.28 (t, J = 12 Hz, 3H), 1.18 130.43, 129.01, 128.71, 127.80, 127.19, 126.54, 125.34, 122.58,
8
4
(
1
1
6
3
13
t, J = 12 Hz, 3H); C NMR (CDCl , 100 MHz) d (ppm) 166.03, 122.12, 121.57, 120.76, 61.29, 60.75, 52.27, 14.03, 13.98; HRMS
59.82, 148.95, 148.69, 133.13, 132.41, 128.30, 127.60, 126.87, m/z calcd for C H BrNO [M ] 456.3291, found 456.3292.
25.80, 124.35, 123.56, 121.39, 118.14, 110.49, 110.00, 61.09,
0.66, 55.88, 13.89, 13.82; HRMS m/z calcd for C22
3
+
23 22 4
4.3.31. Diethyl 1-(5-indane)-4-phenyl-1H-pyrrole-2,3-dicarboxy-
[M ] late. Yellow sticky liquid; H NMR (400 MHz, CDCl
+
1
H
21NO
6
3
) d 7.44 (d, J =
95.4052, found 395.4055.
4 Hz, 2H), 7.28 (t, J = 12 Hz, 2H), 7.21–7.15 (m, 2H), 7.11 (s, 1H),
4
.3.25. Diethyl 1-(benzyl)-4-(3-fluorophenyl)-1H-pyrrole-2,3- 7.03–7.00 (m, 1H), 6.91 (s, 1H), 4.30–4.25 (m, 2H), 4.17–4.11
1
dicarboxylate. Yellow sticky liquid; H NMR (400 MHz, CDCl
d (ppm) 7.30–7.20 (m, 5H), 7.16–1.09 (m, 4H), 6.92 (s, 1H), 5.46 12 Hz, 3H), 1.13 (t, J = 12 Hz, 3H); C NMR (CDCl , 100 MHz) d
s, 2H), 4.30–4.21 (m, 4H), 1.29–1.21 (m, 6H); C NMR (CDCl3, (ppm) 166.04, 159.97, 144.94, 144.43, 137.65, 133.39, 128.46, 128.36,
3
)
(m, 2H), 2.86 (t, J = 12 Hz, 4H), 2.07–2.01 (m, 2H), 1.24 (t, J =
13
3
1
3
(
1
1
1
00 MHz) d (ppm) 166.51, 164.08, 161.64, 160.14, 137.01, 130.05, 128.21, 127.71, 126.88, 125.72, 124.30, 123.90, 121.99, 121.48,
29.96, 128.75, 127.22, 125.66, 123.09, 122.44, 121.51, 114.34, 119.07, 61.02, 60.66, 32.73, 32.47, 25.56, 14.00, 13.86; HRMS m/z
+
13.50, 61.35, 60.77, 52.31, 14.01, 13.99; HRMS m/z calcd for calcd for C25
H
25NO
4
[M ] 403.4703, found 403.4706.
+
C
23 4
H22FNO [M ] 395.4235, found 395.4237.
4
.3.26. Dimethyl 1-(5-indane)-4-phenyl-1H-pyrrole-2,3-dicarb-
1
oxylate. Brown sticky liquid; H NMR (400 MHz, CDCl
3
) d (ppm)
References
7.41 (d, J = 8 Hz, 2H), 7.29 (t, J = 12 Hz, 2H), 7.22–7.16 (m, 2H), 7.11
(
s, 1H), 7.01 (d, J = 8 Hz, 1H), 6.91 (s, 1H), 3.77 (s, 3H), 3.66 (s, 3H),
1 (a) Pyrroles, Part II, ed. R. A. Jones, Wiley, New York, 1992;
(b) Comprehensive Heterocyclic Chemistry II, ed. R. J.
Sundberg, A. R. Katritzky, C. W. Rees and E. F. V. Scriven,
Pergamon Press, Oxford, UK, 1996, vol. 2, p. 119; (c) A. H.
Lipkus, Q. Yuan, K. A. Lucas, S. A. Funk, W. F. Bartelt,
R. J. Schenck and A. J. Trippe, J. Org. Chem., 2008, 73, 4443;
(d) H. Fan, J. Peng, M. T. Hamann and J.-F. Hu, Chem. Rev.,
2008, 108, 264; (e) C. T. Walsh, S. Garneau-Tsodikova and
A. R. Howard-Jones, Nat. Prod. Rep., 2006, 23, 517; ( f ) I. S.
Young, P. D. Thornton and A. Thompson, Nat. Prod. Rep.,
2010, 27, 1801.
13
2
1
1
1
.87 (t, J = 12 Hz, 4H), 2.08–2.03 (m, 2H); C NMR (CDCl3,
00 MHz) d (ppm) 166.53, 160.44, 145.06, 144.55, 137.49, 133.23,
28.39, 127.62, 126.96, 125.96, 124.55, 124.37, 123.82, 121.85,
21.18, 119.13, 52.11, 51.77, 32.74, 32.48, 25.52; HRMS m/z calcd
+
for C23
H
21NO
4
[M ] 375.4171, found 375.4173.
4
.3.27. Dimethyl 1-(4-methoxyphenyl)-4-(2,3-fluorophenyl)-
1
1
H-pyrrole-2,3-dicarboxylate. Yellow sticky liquid; H NMR
(400 MHz, CDCl ) d (ppm) 8.07 (d, J = 8 Hz, 1H), 7.50–7.47
3
(
m, 1H), 7.40 (t, J = 12 Hz, 1H), 7.28–7.16 (m, 5H), 4.04 (s, 3H),
1
3
3
1
1
3
.94 (s, 3H), 3.77 (s, 3H); C NMR (CDCl , 100 MHz) d (ppm)
66.83, 166.76, 159.62, 144.96, 138.31, 131.50, 125.94, 125.07,
24.36, 123.97, 117.83, 117.67, 102.72, 55.73, 53.19, 52.84;
2 E. Bellur, I. Freifeld and P. Langer, Tetrahedron Lett., 2005,
47, 2151–2154.
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3
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G. Daidone, B. Maggio and D. Schillaci, Pharmazie, 1990, 45,
41–442.
(a) A. Kimura, T. Kawara, A. Nakao, A. Ushiyama, S. Shimozato
and T. K. Suzuki, PCT Int Appl. CODEN:PIXXD2, WO 2000001688
ed. J. Q. Yu and Z. J. Shi, Springer, Berlin, 2010, vol. 292;
(m) A. S. Dudnik and V. Gevorgyan, Angew. Chem., Int. Ed., 2010,
49, 2096; (n) B. Li, N. Wang, Y. Liang, S. Xu and B. Wang, Org.
Lett., 2013, 15, 136.
4
A1, 200001132000, 2000, p. 173; (b) D. G. Kaiser and E. M. Glenn, 14 (a) J. Zhu and H. Bienyame, Multicomponent Reactions,
J. Pharm. Sci., 1972, 61, 1908–1911.
A. S. Demir, I. M. Akhmedov and O. Sesenoglu, Tetrahedron,
Wiley-VCH, Weinheim, 2005; (b) I. Nakamura and
Y. Yamamoto, Chem. Rev., 2004, 104, 2127; (c) T. Vlaar,
E. Ruijter, B. U. W. Maes and R. V. A. Orru, Angew. Chem.,
Int. Ed., 2013, 52, 7084; (d) H. Pellissier, Adv. Synth. Catal.,
2012, 354, 237; (e) H. Clavier and H. Pellissier, Adv. Synth.
Catal., 2012, 354, 3347; ( f ) E. Ruijter, R. Scheffelaar and
R. V. A. Orru, Angew. Chem., Int. Ed., 2011, 50, 6234;
(g) B. Jiang, T. Rajale, W. Wever, S. J. Tu and G. Li, Chem. –
Asian J., 2010, 5, 2318; (h) L. A. Wessjohann, D. G. Rivera and
O. E. Vercillo, Chem. Rev., 2009, 109, 796; (i) B. B. Toure
and D. G. Hall, Chem. Rev., 2009, 109, 4439; ( j) D. J. Ramon
and M. Yus, Angew. Chem., Int. Ed., 2005, 44, 1602.
5
6
7
2002, 58, 9793–9799.
H. M. Meshram, B. R. V. Prasad and D. A. Kumar, Tetra-
hedron Lett., 2010, 51, 3477–3480.
F. A. Davis, K. Bowen, H. Xu, V. Velvadapu and C. Ballard,
Tetrahedron, 2008, 64, 4174–4182.
M. Reisser and G. Maas, J. Org. Chem., 2004, 69, 4913–4924.
(a) B. A. Trofimov and N. A. Nedolya, in Comprehensive Hetero-
cyclic Chemistry III, ed. A. R. Katritzky, C. A. Ramsden, E. F. V.
Scriven and R. J. K. Taylor, Elsevier, Oxford, UK, 2008, vol. 3,
p. 45; (b) X. L. Hou, Z. Yang and H. N. C. Wong, Prog. Heterocycl.
8
9
Chem., 2003, 15, 167; (c) S. Yamaguchi and K. Tamao, 15 (a) P. T. Parvatkar, P. S. Parameswaran and S. G. Tilve, Chem. –
J. Organomet. Chem., 2002, 653, 223; (d) V. M. Domingo,
C. Aleman, E. Brillas and L. Julia, J. Org. Chem., 2001,
Eur. J., 2012, 18, 5460; (b) D. Tejedor, D. Gonzalez-Cruz,
A. Santos-Exposito, J. J. Marrero-Tellado, P. de Armas and
F. Garcia-Tellado, Chem. – Eur. J., 2005, 11, 3502; (c) D. L.
Priebbenow, F. M. Pfeffer and S. G. Stewart, Eur. J. Org. Chem.,
2011, 1632; (d) M. J. Bouma, G. Masson and J. Zhu, Eur. J. Org.
Chem., 2012, 475; (e) Y. Liu and J. P. Wan, Chem. – Asian J., 2012,
7, 1488; ( f ) B. Jiang, Q. Y. Li, S. J. Tu and G. Li, Org. Lett., 2012,
14, 5210; (g) M. Presset, Y. Coquerel and Rodriguez, Org. Lett.,
2009, 11, 5706; (h) Y. Ohta, H. Chiba, S. Oishi, N. Fujii and
H. Ohno, J. Org. Chem., 2009, 74, 7052; (i) J. Sun, Y. Sun, H. Gong,
Y. J. Xie and C. G. Yan, Org. Lett., 2012, 14, 5172; ( j) S. Chowdhury,
G. C. Nandi, S. Samai and M. S. Singh, Org. Lett., 2011, 13, 3762;
(k) A. Moyano and R. Rios, Chem. Rev., 2011, 111, 4703.
66, 4058; (e) P. A. Gale, Acc. Chem. Res., 2006, 39, 465;
(
(
f ) S. Michlik and R. Kempe, Nat. Chem., 2013, 5, 140;
g) D. Srimani, Y. Ben-David and D. Milstein, Angew. Chem.,
Int. Ed., 2013, 52, 4012; (h) M. Gao, C. He, H. Chen, R. Bai,
B. Cheng and A. Lei, Angew. Chem., Int. Ed., 2013, 52, 6958.
0 A. Loudet and K. Burgess, Chem. Rev., 2007, 107, 4891.
1 (a) X. Liu, L. Huang, F. Zheng and Z. Zhan, Adv. Synth. Catal.,
1
1
2008, 350, 2778; (b) D. J. Cyr and B. A. Arndtsen, J. Am. Chem.
Soc., 2007, 129, 12366; (c) Y. Lu and B. A. Arndtsen, Angew.
Chem., Int. Ed., 2008, 47, 5430; (d) W. Liu, H. Jiang and
L. Huang, Org. Lett., 2010, 12, 312; (e) S. Maiti, S. Biswas and
U. Jana, J. Org. Chem., 2010, 75, 1674.
16 B. Das, N. Bhunia and M. Lingaiah, Synthesis, 2011, 3471.
12 (a) H. Y. Wang, D. S. Mueller, R. M. Sachwani, R. Kapadia, 17 (a) S. P. Andrews, A. F. Stepan, H. Tanaka, S. V. Ley and
H. N. Londino and L. L. Anderson, J. Org. Chem., 2011,
6, 3203; (b) A. S. Dudnik, A. W. Scromek, M. Rubina,
J. T. Kim, A. V. Kelin and V. Gevorgyan, J. Am. Chem. Soc.,
008, 130, 1440; (c) F. Chen, T. Shen, Y. Cui and N. Jiao, Org.
Lett., 2012, 14, 4926; (d) W. Liu, H. Jiang and L. Huang, Org.
Lett., 2010, 12, 312; (e) H. Dong, M. Shen, J. E. Redford,
B. J. Stokes, A. L. Pumphrey and T. G. Driver, Org. Lett., 2007,
M. D. Smith, Adv. Synth. Catal., 2005, 347, 647; (b) T. Miao
and L. Wang, Tetrahedron Lett., 2007, 48, 95; (c) A. J. Amali and
K. R. Rana, Green Chem., 2009, 11, 1781; (d) M. Cai, G. Zheng,
L. Zha and J. Peng, Eur. J. Org. Chem., 2009, 1585; (e) A. M.
Trzeciak, E. Mieczynska, J. J. Ziolkowski, W. Bukowski,
A. Bukowska, J. Noworol and J. Okal, New J. Chem., 2008,
32, 1124; ( f ) X. Ma, Y. Zhou, J. Zhang, A. Zhu, T. Jiang and
B. Han, Green Chem., 2008, 10, 59; (g) K. Mennecke and
A. Kirschning, Beilstein J. Org. Chem., 2009, 5, 3762.
7
2
9, 5191; ( f ) B. Gabriele, G. Salerno and A. Fazio, J. Org.
Chem., 2003, 68, 7853.
1
3 (a) P. B. Arockiam, C. Bruneau and P. H. Dixneuf, Chem. 18 J. R. Hwu, M. L. Jain, F. Y. Tsai, S. C. Tsay, A. Balakumar and
Rev., 2012, 112, 5879; (b) M. K. Engle, T. S. Mei, M. Wasa and G. H. Hakimelahi, J. Org. Chem., 2000, 65, 5077.
J. Q. Yu, Acc. Chem. Res., 2012, 45, 788; (c) D. A. Colby, 19 (a) V. Nair and A. Deepthi, Chem. Rev., 2007, 107, 1862;
A. S. Tsai, R. G. Bergman and J. A. Ellman, Acc. Chem. Res.,
012, 45, 814; (d) G. Song, F. Wang and X. Li, Chem. Soc.
(b) S. Vellaisamy and J. C. Meneendez, Org. Lett., 2008, 10, 4303;
(c) K. T. Pradip and M. Chhanda, ARKIVOC, 2011, 10, 287.
2
Rev., 2012, 41, 3651; (e) L. Ackermann, Chem. Rev., 2011, 20 A. B. Atar, S. D. Dindulkar and Y. T. Jeong, Monatsh. Chem.,
11, 1315; ( f ) J. Wencel-Delord, T. Droge, F. Liu and F. Glorius, 2013, 144, 695.
Chem. Soc. Rev., 2011, 40, 4740; (g) A. E. Wendlandt, A. M. Suess 21 A. B. Atar, Y. S. Jeong and Y. T. Jeong, Tetrahedron, 2014,
and S. S. Stahl, Angew. Chem., Int. Ed., 2011, 50, 11062; 70, 5207.
h) C. L. Sun, B. J. Li and Z. J. Shi, Chem. Rev., 2011, 22 A. B. Atar and Y. T. Jeong, Mol. Diversity, 2014, 18, 389.
11, 1293; (i) P. Herrmann and T. Bach, Chem. Soc. Rev., 23 A. B. Atar, J. Oh, J. T. Kim and Y. T. Jeong, Monatsh. Chem.,
011, 40, 2022; ( j) C. S. Yeung and V. M. Dong, Chem. Rev., 2014, 145, 329.
011, 111, 1215; (k) S. H. Cho, J. Y. Kim, J. Kwak and S. Chang, 24 R. H. Jih, L. J. Moti, T. Fu-Yuan, T. Shwu-Chen, B. Arumugham
Chem. Soc. Rev., 2011, 40, 5068; (l) Topics in Current Chemistry, and H. H. Gholam, J. Org. Chem., 2000, 65, 5077.
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