Multicomponent formation of fused pyrroles through p-TsOH promoted N-arylation

Article abstract of DOI:10.1016/j.tet.2013.02.026

Concise and efficient N-arylation-based domino [3+2] heterocyclization promoted by p-TsOH has been established for the synthesis of 27 examples of 3-arylamino substituted fused pyrrole derivatives in 70-90% yields. The present methodology shows attractive

Full text of DOI:10.1016/j.tet.2013.02.026

Tetrahedron 69 (2013) 2941e2946
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Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Multicomponent formation of fused pyrroles through p-TsOH
promoted N-arylation
*
*
Ying Li, Qiu-Yun Li, Hai-Wei Xu, Wei Fan, Bo Jiang , Shu-Liang Wang, Shu-Jiang Tu
School of Chemistry and Chemical Engineering, and Jiangsu Key Laboratory of Green Synthetic Chemistry for Functional Materials, Jiangsu Normal
University, Xuzhou 221116, Jiangsu, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
Concise and efficient N-arylation-based domino [3þ2] heterocyclization promoted by p-TsOH has been
established for the synthesis of 27 examples of 3-arylamino substituted fused pyrrole derivatives in
70e90% yields. The present methodology shows attractive properties, such as mild reaction conditions,
concise one-pot operation, short reaction periods of 15e30 min, and easy purification. It can avoid time-
consuming and costly syntheses, tedious work-up procedures and isolation of intermediate.
Ó 2013 Elsevier Ltd. All rights reserved.
Received 29 November 2012
Received in revised form 26 January 2013
Accepted 4 February 2013
Available online 14 February 2013
Keywords:
Three-component reactions
3-Arylamino fused pyrrole
Microwave heating
N-arylation
1. Introduction
alkynes in the presence of metal-catalysts,10 and 1,3-dipolar cy-
11
€
cloadditions of muchnone derivatives. The development of al-
The selective direct N-arylation, which provides an appealing
way for the synthesis of valuable nitrogen-containing compounds,
represents one of the formidable challenges in synthetic organic
chemistry.1 For over a century, N-arylation of amines has attracted
wide attention, and the copper-catalyzed Ullmann/Goldberg-type
N-arylations2e4 and palladium-catalyzed BuchwaldeHartwig cou-
plings5 are popular methods known so far. Obviously, there has
been an urgent demand for the design of a green and sustainable N-
arylation cascade, since the transition metals involved in these
procedures are generally thought not to be environmentally
friendly. Therefore, the development of an efficient and broadly
applicable intermolecular N-arylation without the use of metal-
catalysts is more desirable.
ternative step-economical methods for the assembly of these
heterocyclic cores, producing less wastes and by-products, con-
tinues to be of great interest and challenging.
Recently, our group and others have developed a series of multi-
component domino reactions (MDRs) for poly-heterocycles of
chemical and pharmaceutical interest.12e14 We also established
new allylic amination to form fused pyrrole derivatives.12g In this
reaction N-aryl enaminones were converted into the desired allylic
ammoniated products 5 (Scheme 1) whereas N-carboxymethyl
counterparts occurred in N-arylation direction to yield fused pyr-
roles 6. Compared with acidity of acetic acid, N-carboxymethyl
enaminones possess stronger acidity due to the field effect of its
On the other hand, fused pyrroles widely exist in nature. They
often serve as ‘privileged structures’ in many biologically active
molecules and pharmaceutical substances. These compounds have
been widely used as building blocks in total synthesis of many
natural products and have displayed biological activities, such as
powerful antibacterial, antiviral, anti-inflammatory, antitumor, and
antioxidant activities.6 In the past several decades, many method-
ologies for the synthesis of fused pyrroles have been developed.
Most of them involved rearrangement-cyclization of alkynol,7
alkynyl ketones,8 cycloketone annulations,9 cascade cyclization of
* Corresponding authors. Tel./fax: þ86 516 83500065; e-mail addresses:
jiangchem@xznu.edu.cn (B. Jiang), laotu@xznu.edu.cn, laotu2001@263.net
(S.-J. Tu).
Scheme 1. Domino synthesis of fused pyrroles.
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.02.026

2942
Y. Li et al. / Tetrahedron 69 (2013) 2941e2946
amino group.15 Therefore, it can be inferred that the selectivity of
MDR was controlled by the acidity of media. During the continua-
tion of this project, we envisioned that the reaction can be directed
toward N-arylation to form fused pyrrole derivatives using stronger
Brønsted acid catalysts.
Table 2
Domino synthesis of fused pyrroles 4 under MWa
With this notion in mind, the one-pot reaction of arylglyoxal
monohydrate, N-aryl enaminones, and aromatic amines was per-
formed to achieve this type of intermolecular N-arylation. We chose
p-toluene sulphonic acid (p-TsOH) as an acid catalyst to investigate
these N-arylation-based MDRs, due to its stronger acidity and easy
availability and it has been widely used in heterocyclic syntheses.16
Surprisingly to our delight, N-arylation occurred very easily in the
presence of p-TsOH. Herein, we would like to disclose this new N-
arylation-based domino reaction for the synthesis of 3-arylamino
substituted fused pyrroles 4 (Scheme 1). The attractive aspect of the
present domino reaction is shown by the fact that the construction of
pyrrole skeleton and the direct N-arylation of amines were readily
achieved in an intermolecular fashion in a one-pot operation.
Entry 4
Ar
Ar1
Ar2
R1 Time/min Yieldb/%
1
2
3
4
4a 4-MePh (1a) Ph (2a)
4b 4-MePh (1a) Ph (2a)
4c 4-MePh (1a) 4-ClPh (2b)
4d 4-MePh (1a) 4-BrPh (2c)
4-ClPh (3a)
4-BrPh (3b)
4-NO2Ph (3c) Me 16
Me 18
Me 25
79
77
88
84
70
77
75
90
78
72
80
81
78
89
79
78
76
85
74
82
89
86
73
82
74
78
80
4-ClPh (3a)
Me 20
Me 24
Me 22
Me 15
5
4e 4-MePh (1a) 3,4-Cl2Ph (2d) 4-BrPh (3b)
6
7
8
9
4f 4-MeOPh (1b) Ph (2a)
4g 4-MeOPh (1b) Ph (2a)
4h 4-MeOPh (1b) Ph (2a)
4i 4-MeOPh (1b) 4-ClPh (2b)
4j 4-MeOPh (1b) 4-BrPh (2c)
4-ClPh (3a)
4-BrPh (3b)
4-NO2Ph (3c) Me 15
4-BrPh (3b)
4-ClPh (3a)
Me 15
Me 20
Me 25
Me 20
Me 25
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
4k 4-MeOPh (1b) 4-MePh (2e) 4-ClPh (3a)
4l 4-FPh (1c)
4m 4-ClPh (1d)
4n 4-ClPh (1d)
4o 4-ClPh (1d)
4p 4-ClPh (1d)
4q 4-BrPh (1e)
4r 4-BrPh (1e)
4s Ph (1f)
4t Ph (1f)
4u Ph (1f)
4v Ph (1f)
4w Ph (1f)
4-ClPh (2b)
4-ClPh (2b)
4-ClPh (2b)
4-BrPh (2c)
4-BrPh (2c)
Ph (2a)
4-BrPh (3b)
4-BrPh (3b)
4-NO2Ph (3c) Me 22
4-ClPh (3a)
4-BrPh (3b)
4-ClPh (3a)
4-NO2Ph (3c) Me 18
4-BrPh (3b)
4-BrPh (3b)
4-NO2Ph (3c) Me 20
3,4-Cl2Ph (3d) Me 28
4-ClPh (3a)
2. Results and discussion
Me 28
Me 20
Me 30
We devoted our efforts on this study by using the reaction of 4-
tolylglyoxal monohydrate 1a,
a preformed 5,5-dimethyl-3-
4-ClPh (2b)
Ph (2a)
phenylaminocyclohex-2-enone 2a and 4-chlorobenzenamine 3a,
as the model reaction. Experiments were carried out in EtOH using
various catalysts (1.0 equiv), such as p-TsOH, KHSO4, H3PO4, and
Sulfamic acid (NH2SO2H) at 80 ꢀC in search of suitable conditions
under microwave (MW) irradiation. The results of these compara-
tive experiments are summarized in Table 1. From the results it is
obvious that p-TsOH (entry 4) demonstrated superior catalytic ac-
tivity and is the best catalyst among those examined. In order to
further evaluate the influence of p-TsOH concentration, the reaction
was performed in EtOH and repeated many times using different
amounts of p-TsOH in a sealed vessel under microwave irradiation
for 18 min. The yield of 4a was leveled off when more than 1.0 equiv
of p-TsOH was used as a promoter, whereas 0.5 equiv decreased the
yield of 4a.
Me 30
Me 26
4-ClPh (2b)
4-ClPh (2b)
4-ClPh (2b)
4-BrPh (2c)
4-BrPh (2c)
Me 20
4x Ph (1f)
4y 4-MePh (1a) 4-BrPh (2f)
4z 4-ClPh (1d)
4aa 4-BrPh (1e)
4-NO2Ph (3c) Me 25
4-ClPh (3a)
4-ClPh (3a)
4-ClPh (3a)
H
H
H
28
30
26
4-BrPh (2f)
4-BrPh (2f)
a
Reagents and conditions: 80 ꢀC, EtOH (1.5 mL) microwave heating.
Isolated yield.
b
good to excellent yields. The unsubstituted arylglyoxal monohydrate
1f was reacted with different N-aryl enaminones and aromatic
amines and obtained the corresponding fused pyrroles 4sex in
73e89% yields (Table 2, entries 19e24). Next, to further examine the
generality of this reaction system, various amine substrates 3 were
used to give the corresponding arylamino substituted fused pyrroles
through metal-free intermolecular N-arylation. 4-Nitrophenylamine
3c was also suitable for this domino reaction. As an extension of the
above study, 5,5-unsubstituted enaminones 2f was subjected with
3a and diverse arylglyoxal monohydrates to investigate the possi-
bility of this transformation. Substituents on the phenyl ring of
arylglyoxal monohydrates were all successfully engaged in this re-
action, leading to the final products with good yields (4ze4aa)
(Scheme 2). Furthermore, groups like bromide and chloride were
well tolerated. These functional groups provide ample opportunity
for further functional group manipulations, for example, such as
modern cross-coupling reactions. It can be noted that this protocol
provides a straightforward pathway to N-arylation of amines, which
are generally prepared via metal-catalyzed coupling reactions.4,5
Table 1
Optimization of the catalysts for compound 4a
Entry
Catalyst (equiv)
Time (min)
Yield (%)
1
2
3
4
5
6
KHSO4 (1.0)
H3PO4 (1.0)
Sulfamic acid (1.0)
p-TsOH (1.0)
p-TsOH (0.5)
p-TsOH (1.5)
18
18
18
18
18
18
53
68
70
79
65
79
With these optimized conditions in hand, we explored the scope
of this intermolecular N-arylation process by using various easily
available starting materials. The results are summarized in Table 2.
All the reactions were finished in 15e30 min. A series of valuable 3-
arylamino fused pyrroles were synthesized in high yields. The re-
action promoted by p-TsOH is easy to perform simply by heating
a mixture of cyclic enaminones with 1 and 3 in EtOH under micro-
wave irradiation. We found that the reactant can not only be aryl-
glyoxal monohydrate 1cee, which possess electron-withdrawing
substituents, such as fluoro, bromo, and chloro groups at the para
position of the benzene ring, but also be 1a and 1b having electron-
donating substituents, such as methyl and methoxy groups to give
the corresponding 3-arylamino fused pyrrole derivatives 4aer in
Scheme 2. Domino synthesis of fused pyrroles 4ze4aa.
In all the cases, the functional complexity of resulting products
from this new reaction pathway illustrates the remarkable

Y. Li et al. / Tetrahedron 69 (2013) 2941e2946
2943
selectivity of the sequence starting from very common and easily
accessible inexpensive starting materials. The structural elucida-
tion was unequivocally determined by NMR spectroscopic analysis.
In order to further ascertain the structures of the newly synthesized
fused pyrrole derivatives (4), single crystal of 4h was successfully
obtained with its structure unambiguously confirmed by X-ray
diffraction analysis (Fig. 1). Furthermore, water is nearly a sole by-
product, which makes the work-up more convenient. In most cases,
the products were precipitated out after the completion of reaction.
With this process, the formation of pyrrole skeleton and its N-
arylation were readily achieved via p-TsOH promoted three-
component domino reaction in a one-pot operation.
aromatic amines has been developed in this work. The mild condi-
tions, the maximum efficiency of a process and short reaction periods
aswellas operationalsimplicityareclearlyrepresentedinthis one-pot
transformation that provides an elegant methodology for the syn-
thesis of highly functionalized fused pyrroles. Further investigations
to evaluate the applicability of this process to a broad range of sub-
strates, synthesizing more complex products and testing their bi-
ological activity is an ongoing goal of research in our laboratory.
4. Experimental section
4.1. General
Microwave irradiation was carried out with initiator from
Biotage Company, Sweden. Melting points were determined in
open capillaries and were uncorrected. IR spectra were taken on
a FTIR-Tensor 27 spectrometer in KBr pellets and reported in cmꢁ1
.
1H NMR spectra were measured on a Bruker DPX 400 MHz spec-
trometer in CDCl3 with chemical shift ( ) given in parts per million
d
relative to TMS as internal standard. HRMS (ESI) was determined by
using microTOF-Q II HRMS/MS instrument (Bruker). X-ray crystal-
lographic analysis was performed with a Siemens SMART CCD and
a Siemens P4 diffractometer.
4.1.1. Typical procedure for the preparation of 3-((4-chlorophenyl)
amino)-6,6-dimethyl-1-phenyl-2-(p-tolyl)-6,7-dihydro-1H-indol-
4(5H)-one (4a). Typically, 2,2-dihydroxy-1-p-tolyl-ethanone (1a,
1 mmol, 0.166 g, 1.0 equiv) was introduced in a 10-mL InitiatorÔ
reaction vial, 5,5-dimethyl-3-phenylamino-cyclohex-2-enone (2a,
1.0 mmol, 0.215 g, 1.0 equiv), 4-chlorobenzenamine (3a, 1.0 mmol,
0.127 g, 1.0 equiv), and p-TsOH (1.0 mmol, 0.190 g, 1.0 equiv) as well
as EtOH (1.5 mL) were then successively added. Subsequently, the
reaction vial was closed and then pre-stirred for 10 s. The mixture
was irradiated (Time: 18 min, Temperature: 80 ꢀC; Absorption
level: High; Fixed Hold Time) until TLC (petroleum ether/acetone
3:1) revealed that conversion of the starting material 1a was
complete. The reaction mixture was then cooled to room temper-
ature and then diluted with cold water (20 mL). The solid product
Fig. 1. ORTEP drawing of 4h.17
On the basis of all the above results, reasonable mechanism has
been proposed for the formation of multifunctionalized fused
pyrrole 4 as shown in Scheme 3. The reaction involves the ring
closure cascade processes that consist of initial condensation and
protonation of imine (1 to A), intermolecular nucleophilic addition
(A to B), intramolecular proton transfer (B to C), and cyclization (D
to 4). With stronger acidity of the catalyst, the reaction favors
protonation of imine in the presence of p-TsOH (B to C). This would
prevent isomerization to form enamine intermediate and further
give allylic amination product 5.12g
€
was collected by Buchner filtration and was purified by re-
crystallization from 95% EtOH to afford the desired pure fused
pyrroles 4a as a white solid (0.359 g, yield 79%, mp: 205e205.4 ꢀC).
A white solid; mp: 205e205.4 ꢀC; 1H NMR (400 MHz, CDCl3)
d
7.40e7.36 (m, 3H, ArH, 2H and NH, 1H), 7.13e7.11 (m, 2H, ArH),
6.90e6.84 (m, 7H, ArH), 6.53 (d, J¼8.8 Hz, 2H, ArH), 2.50 (s, 2H,
CH2), 2.38 (s, 2H, CH2), 2.19 (s, 3H, CH3), 1.10 (s, 6H, CH3) 13C NMR
(100 MHz, CDCl3)
128.7, 128.2, 128.2, 128.0,128.0,124.3,124.0, 123.3, 116.8,113.0, 52.3,
37.0, 35.5, 28.6, 21.2; IR (KBr,
cmꢁ1): 3313, 1646, 1595, 1557, 1495,
d 194.8, 143.4, 141.6, 137.6, 136.4, 129.2, 128.9,
n
1442, 1367, 1284, 1170, 1069, 1002, 814, 771, 702; HRMS (ESI): m/z
calcd for C29H28ClN2O, 455.1890 [MþH]þ, found: 455.1860.
4.1.2. 3-((4-Bromophenyl)amino)-6,6-dimethyl-1-phenyl-2-(p-
tolyl)-6,7-dihydro-1H-indol-4(5H)-one (4b). A white solid; mp:
208.7e209 ꢀC; 1H NMR (400 MHz, CDCl3)
d 7.45e7.31 (m, 3H, ArH,
2H and NH, 1H), 7.14e7.08 (m, 2H, ArH), 7.03 (d, J¼8.8 Hz, 2H, ArH),
6.84 (s, 5H, ArH), 6.48 (d, J¼8.8 Hz, 2H, ArH), 2.50 (s, 2H, CH2), 2.38 (s,
2H, CH2), 2.19 (s, 3H, CH3), 1.10 (s, 6H, CH3) 13C NMR (100 MHz,
CDCl3)
128.2, 128.0, 127.9, 124.5, 123.8, 117.2, 113.0, 110.6, 52.3, 37.0, 35.5,
28.7, 21.2; IR (KBr,
cmꢁ1): 3301, 2959,1643, 1594, 1582, 1536, 1493,
d 194.8, 143.9, 141.7, 137.5, 136.4, 131.1, 129.2, 128.9, 128.8,
n
Scheme 3. The reasonable mechanism for the formation of 4.
1442,1424,1397,1308,1232,1093,1075,1015, 832, 814; HRMS (ESI):
3. Conclusion
m/z calcd for C29H28BrN2O, 499.1207 [MþH]þ, found: 499.1219.
In summary, an operationally simple and highly efficient p-TsOH
promoted N-arylation strategy for the three-component assembly of
fused pyrroles from enaminones, arylglyoxal monohydrates, and
4.1.3. 1-(4-Chlorophenyl)-6,6-dimethyl-3-((4-nitrophenyl)amino)-2-
(p-tolyl)-6,7-dihydro-1H-indol-4(5H)-one (4c). A yellow solid; mp:
223e224 ꢀC; 1H NMR (400 MHz, CDCl3)
d
7.86 (d, J¼9.2 Hz, 2H),

2944
Y. Li et al. / Tetrahedron 69 (2013) 2941e2946
7.43e7.35 (m, 3H), 7.12 (dd, J¼6.7, 2.9 Hz, 2H), 6.87 (q, J¼8.3 Hz,
4H), 6.63e6.41 (m, 2H), 2.53 (s, 2H), 2.39 (s, 2H), 2.20 (s, 3H), 1.11
HRMS (ESI): m/z calcd for C29H26ClN3O4, 481.2002 M, found:
481.2009.
(s, 6H) 13C NMR (100 MHz, CDCl3)
d
194.7, 150.6, 142.1, 139.0, 137.2,
137.1, 129.4, 129.0, 128.5, 128.0, 127.3, 126.4, 125.4, 121.0, 113.7,
113.3, 52.3, 36.9, 35.6, 28.6, 21.2; IR (KBr,
cmꢁ1): 3303, 2959,
4.1.9. 3-((4-Bromophenyl)amino)-1-(4-chlorophenyl)-2-(4-
methoxyphenyl)-6,6-dimethyl-6,7-dihydro-1H-indol-4(5H)-one
(4i). A white solid; mp: 202.8e203.2 ꢀC; 1H NMR (400 MHz, CDCl3)
n
1663, 1595, 1524, 1497, 1449, 1295, 1276, 1112, 1040, 831, 752, 701;
HRMS (ESI): m/z calcd for C29H27ClN3O3, 500.1741 [MþH]þ, found:
500.1734.
d
7.39e6.37 (m, 3H, ArH, 2H and NH, 1H),7.15e7.08 (m, 2H, ArH),
7.03 (d, J¼8.8 Hz, 2H, ArH), 6.87 (d, J¼8.8 Hz, 2H, ArH), 6.59 (d,
J¼8.8 Hz, 2H, ArH), 6.49 (d, J¼8.8 Hz, 2H, ArH), 2.50 (s, 2H, CH2),
4.1.4. 1-(4-Bromophenyl)-3-((4-chlorophenyl)amino)-6,6-dimethyl-
2.37 (s, 2H, CH2),1.10 (s, 3H, CH3) 13C NMR (100 MHz, CDCl3)
d 194.8,
2-(p-tolyl)-6,7-dihydro-1H-indol-4(5H)-one (4d). A white solid;
158.2, 143.9, 141.4, 137.5, 131.1, 130.4, 129.2, 128.2, 128.1, 124.1, 123.5,
mp: 178e178.3 ꢀC; 1H NMR (400 MHz, CDCl3)
d
7.50 (d, J¼7.6 Hz,
123.3, 117.3, 113.6, 112.9, 110.6, 55.1, 52.3, 37.0, 35.5, 28.6; IR (KBr, n
2H, ArH), 6.99 (d, J¼8.8 Hz, 3H, ArH, 2H and NH, 1H), 6.89e6.81 (m,
6H, ArH), 6.51 (d, J¼8.0 Hz, 2H, ArH), 2.49 (s, 2H, CH2), 2.37 (s, 2H,
cmꢁ1): 3313, 2957, 1659, 1560, 1498, 1444, 1291, 1251, 1178, 1109,
1069, 1028, 814, 771, 702; HRMS (ESI): m/z calcd for
C29H25BrClN2O2, 547.0782 [MꢁH]ꢁ, found: 547.0764.
CH2), 2.21 (s, 3H, CH3),1.10 (s, 6H, CH3); IR (KBr, n
cmꢁ1): 3301, 2959,
1654, 1602, 1585, 1537, 1485, 1444, 1396, 1367, 1302, 1107, 1068,
1013, 823, 814; HRMS (ESI): m/z calcd for C29H25BrClN2O,
533.0814.0422 [MꢁH]ꢁ, found: 533.0791.
4.1.10. 1-(4-Bromophenyl)-3-((4-chlorophenyl)amino)-2-(4-
methoxyphenyl)-6,6-dimethyl-6,7-dihydro-1H-indol-4(5H)-one
(4j). A white solid; mp: 176.1e176.7 ꢀC; 1H NMR (400 MHz, CDCl3)
4.1.5. 3-((4-Bromophenyl)amino)-1-(3,4-dichlorophenyl)-6,6-
d
7.50 (d, J¼7.8 Hz, 2H, ArH), 6.98 (d, J¼7.6 Hz, 2H, ArH), 6.90e6.85
dimethyl-2-(p-tolyl)-6,7-dihydro-1H-indol-4(5H)-one (4e). A white
(m, 5H, ArH, 4H and NH, 1H), 6.61 (d, J¼8.0 Hz, 2H, ArH), 6.52 (d,
J¼8.0 Hz, 2H, ArH), 3.70 (s, 3H, CH3), 2.49 (s, 2H, CH2), 2.37 (s, 2H,
solid; mp: 178.1e178.9 ꢀC; 1H NMR (400 MHz, CDCl3)
d 7.42 (d,
J¼8.5 Hz, 2H), 7.27 (d, J¼2.1 Hz, 2H), 7.02 (q, J¼8.4 Hz, 6H), 6.91
CH2), 1.10 (s, 6H, CH3) 13C NMR (101 MHz, CDCl3)
d 194.8, 158.4,
(dd, J¼8.5, 2.3 Hz, 2H), 2.49 (s, 2H), 2.39 (s, 2H), 2.29 (s, 3H), 1.09 (s,
143.0, 136.6, 132.5, 130.8, 130.4, 129.5, 128.2, 123.1, 117.0, 113.7, 55.1,
52.2, 37.0, 35.5, 28.6, 26.6; IR (KBr,
6H) 13C NMR (100 MHz, CDCl3)
d
192.6, 141.5, 140.5, 137.0, 136.5,
n
cmꢁ1): 3306, 2958, 1645, 1568,
133.1, 132.3, 130.9, 129.5, 129.2, 128.9, 127.3, 126.4, 123.9, 113.0,
1490, 1420, 1289, 1252, 1175, 1070, 1011, 831, 815; HRMS (ESI): m/z
calcd for C29H25BrClN2O2, 547.0782 [MꢁH]ꢁ, found: 547.0783.
70.1, 52.7, 37.2, 35.3, 28.5, 21.2, 15.4; IR (KBr,
n
cmꢁ1): 3305, 2953,
1662, 1560, 1477, 1530, 1420. 1291, 1066, 1051, 875, 831; HRMS
(ESI): m/z calcd for C29H24BrCl2N2O, 567.0422 [MꢁH]ꢁ, found:
567.0420.
4.1.11. 3-((4-Chlorophenyl)amino)-2-(4-methoxyphenyl)-6,6-
dimethyl-1-(p-tolyl)-6,7-dihydro-1H-indol-4(5H)-one (4k). A white
solid; mp: 160e161 ꢀC; 1H NMR (400 MHz, CDCl3)
d 7.28 (s, 1H, NH),
4.1.6. 3-((4-Chlorophenyl)amino)-2-(4-methoxyphenyl)-6,6-
7.19 (d, J¼6.4 Hz, 2H, ArH), 7.01 (d, J¼7.2 Hz, 2H, ArH), 6.91 (d,
J¼7.2 Hz, 4H, ArH), 6.62e6.54 (m, 4H, ArH), 3.71 (s, 3H, CH3), 2.51 (s,
2H, CH2), 2.40 (s, 3H, CH3), 2.19 (s, 2H, CH2), 1.11 (s, 6H, CH3) 13C
dimethyl-1-phenyl-6,7-dihydro-1H-indol-4(5H)-one (4f). A white
solid; mp:158e159 ꢀC; 1H NMR (400 MHz, CDCl3)
d 7.37 (s, 3H, ArH,
2H and NH, 1H), 7.12e7.11 (m, 3H, ArH), 6.90e6.86 (m, 4H, ArH),
6.59e6.53 (m, 4H, ArH), 2.50 (s, 2H, CH2), 2.38 (s, 2H, CH2), 1.10 (s,
NMR (100 MHz, CDCl3)
52.3, 37.0, 35.5, 28.6, 26.6, 21.2; IR (KBr,
1556, 1513, 1445, 1416, 1292, 1182, 1088, 1042, 809; HRMS (ESI): m/z
calcd for C30H28ClN2O2, 483.1833 [MꢁH]ꢁ, found: 483.1866.
d
130.4, 129.8, 128.2, 127.8, 116.8, 113.5, 55.1,
n
cmꢁ1): 3334, 2960, 1666,
6H, CH3) 13C NMR (100 MHz, CDCl3)
d
194.8, 159.3, 158.2, 130.8,
130.4, 129.2, 128.7, 128.7, 128.4, 128.3, 128.2, 128.1, 123.4, 123.4,
117.8, 116.9, 113.6, 112.9, 55.1, 53.6, 52.3, 37.0, 35.5, 28.6, 26.6; IR
(KBr,
n
cmꢁ1): 3316, 2955, 1658, 1559, 1503, 1444, 1369, 1288, 1249,
4.1.12. 3-((4-Bromophenyl)amino)-1-(4-chlorophenyl)-2-(4-
1181, 1025, 834, 817, 769, 700; HRMS (ESI): m/z calcd for
fluorophenyl)-6,6-dimethyl-6,7-dihydro-1H-indol-4(5H)-one (4l). A
C29H26ClN2O2, 469.1677 [MꢁH]ꢁ, found: 469.1690.
white solid; mp: 173.5e173.9 ꢀC; 1H NMR (400 MHz, CDCl3)
d 7.37 (d,
J¼8.0 Hz, 2H), 7.05e7.00 (m, 4H), 6.93e6.88 (m, 2H), 6.79e6.75 (m,
4.1.7. 3-((4-Bromophenyl)amino)-2-(4-methoxyphenyl)-6,6-
2H), 6.45 (d, J¼8.4 Hz, 2H), 2.49 (s, 2H), 2.38 (s, 2H), 1.10 (s, 6H) 13C
dimethyl-1-phenyl-6,7-dihydro-1H-indol-4(5H)-one (4g). A white
NMR (100 MHz, CDCl3)
d
194.96, 161.42 (J1CF¼246.4 Hz), 143.01,
solid; mp: 198e199 ꢀC; 1H NMR (400 MHz, CDCl3)
d
7.37 (s, 4H, ArH,
141.65 (s, 0H), 135.77 (s, 0H), 134.36 (s, 0H), 131.11 (s, 1H), 130.79 (d,
J¼8.1 Hz, 1H), 129.64 (s, 1H), 129.22 (s, 1H), 126.88 (d, J¼3.4 Hz, 0H),
124.66 (s, 0H), 122.18 (s, 0H), 117.58 (s, 1H), 115.32 (J2CF¼21.4 Hz),
3H and NH, 1H), 7.11e7.10 (m, 2H, ArH), 7.03 (d, J¼7.6 Hz, 2H, ArH),
6.87 (d, J¼7.6 Hz, 2H, ArH), 6.59 (d, J¼7.6 Hz, 2H, ArH), 6.49 (d,
J¼7.6 Hz, 2H, ArH), 3.68 (s, 3H, CH3), 2.50 (s, 2H, CH2), 2.37 (s, 2H,
112.96,111.11, 52.19, 36.96, 35.53, 28.64; IR (KBr, n
cmꢁ1): 3335, 2959,
CH2), 1.10 (s, 6H, CH3) 13C NMR (100 MHz, CDCl3)
d
194.8, 158.2,
1654,1584,1537,1515,1445,1367,1257,1068,1013, 815; HRMS (ESI):
143.8, 143.7, 137.5, 131.1, 130.4, 129.2, 128.4, 128.2, 128.1, 123.3, 118.1,
117.3, 113.7, 113.5, 112.9, 110.6, 55.1, 52.3, 37.0 35.5, 28.6, 26.6; IR
m/z calcd for C28H22FClBrN2O, 537.0563 [MꢁH]ꢁ, found: 537.0557.
(KBr,
n
cmꢁ1): 3326, 2957, 1655, 1594, 1480, 1443, 1291, 1360, 1178,
4.1.13. 3-((4-Bromophenyl)amino)-1,2-bis(4-chlorophenyl)-6,6-
1069, 1028, 836, 771; HRMS (ESI): m/z calcd for C29H26BrN2O2,
dimethyl-6,7-dihydro-1H-indol-4(5H)-one (4m). A white solid; mp:
513.1172 [MꢁH]ꢁ, found: 513.1139.
168e170 ꢀC; 1H NMR (400 MHz, CDCl3)
d 7.40 (s, 3H, ArH, 2H and
NH, 1H), 7.11 (s, 2H, ArH), 7.06e6.97 (m, 4H, ArH), 6.87 (d, J¼7.6 Hz,
4.1.8. 2-(4-Methoxyphenyl)-6,6-dimethyl-3-((4-nitrophenyl)amino)-
2H, ArH), 6.47 (d, J¼7.6 Hz, 2H, ArH), 2.49 (s, 2H, CH2), 2.38 (s, 2H,
1-phenyl-6,7-dihydro-1H-indol-4(5H)-one (4h). A yellow solid; mp:
CH2), 1.10 (s, 6H, CH3) 13C NMR (100 MHz, CDCl3)
d 195.0, 137.2,
209e209.3 ꢀC; 1H NMR (400 MHz, CDCl3)
ArH), 7.40 (s, 3H, ArH), 7.13e7.12 (m, 3H, ArH, 2H and NH, 1H), 6.89
(d, J¼8.0 Hz, 2H, ArH), 6.63e6.55 (m, 4H, ArH), 3.68 (s, 3H, CH3),
2.53 (s, 2H, CH2), 2.39 (s, 2H, CH2), 1.11 (s, 6H, CH3) 13C NMR
d
7.87 (d, J¼8.8 Hz, 2H,
132.4, 131.2, 130.1, 129.5, 128.5, 128.2, 128.0, 117.5, 112.8, 52.2, 36.9,
35.5, 28.6; IR (KBr,
n
cmꢁ1): 3353, 2958,1667,1594,1572,1556,1495,
1486, 1443, 1367, 1283, 1170, 1102, 814, 728, 697; HRMS (ESI): m/z
calcd for C28H24Cl2BrN2O, 555.0422 [MþH]þ, found: 555.0425.
(100 MHz, CDCl3)
129.4, 128.5, 128.0, 126.2, 125.4, 122.6, 120.8, 113.9, 113.7, 113.3,
55.1, 52.3, 36.9, 35.6, 28.6; IR (KBr,
cmꢁ1): 3313, 2959, 1661, 1597,
1557, 1502, 1451, 1369, 1325, 1251, 1180, 1113, 1025, 836, 752;
d 194.7, 158.7, 150.6, 141.9, 139.1, 137.1, 130.4,
4.1.14. 1,2-Bis(4-chlorophenyl)-6,6-dimethyl-3-((4-nitrophenyl)
n
amino)-6,7-dihydro-1H-indol-4(5H)-one (4n). A yellow solid; mp:
176e176.4 ꢀC; 1H NMR (400 MHz, CDCl3)
d
7.88 (d, J¼8.4 Hz, 2H,

Y. Li et al. / Tetrahedron 69 (2013) 2941e2946
2945
ArH), 7.42 (s, 3H, ArH, 2H and NH, 1H), 7.17e7.00 (m, 4H, ArH), 6.90
(d, J¼7.6 Hz, 2H, ArH), 6.55 (d, J¼8.4 Hz, 2H, ArH), 2.52 (s, 2H, CH2),
HRMS (ESI): m/z calcd for C28H24BrN2O, 485.1050 [MꢁH]ꢁ, found:
485.1093.
2.40 (s, 2H, CH2),1.11 (s, 6H, CH3) 13C NMR (100 MHz, CDCl3)
d 194.8,
150.1,142.6,139.4,136.8,133.3,130.1,129.6,128.7,127.9,125.5,121.9,
4.1.20. 3-((4-Bromophenyl)amino)-1-(4-chlorophenyl)-6,6-
113.8, 113.3, 52.2, 36.9 35.6, 28.6; IR (KBr,
n
cmꢁ1): 3326, 2942, 1655,
dimethyl-2-phenyl-6,7-dihydro-1H-indol-4(5H)-one (4t). A white
1603, 1577, 1563, 1538, 1496, 1488, 1452, 1420, 1338, 1304, 1260,
1112, 835, 774, 745; HRMS (ESI): m/z calcd for C28H24Cl2N3O3,
520.1195 [MþH]þ, found: 520.1187.
solid; mp: 183e184 ꢀC; 1H NMR (400 MHz, CDCl3)
d 7.35 (d,
J¼8.8 Hz, 2H, ArH), 7.13e7.03 (m, 5H, ArH, 4H and NH, 1H), 7.00 (d,
J¼8.8 Hz, 2H, ArH), 6.96e6.87 (m, 2H, ArH), 6.45 (d, J¼8.8 Hz, 2H,
ArH), 2.50 (s, 2H, CH2), 2.38 (s, 2H, CH2), 1.11 (s, 6H, CH3) 13C NMR
4.1.15. 1-(4-Bromophenyl)-2-(4-chlorophenyl)-3-((4-chlorophenyl)
(100 MHz, CDCl3)
129.5, 129.2, 129.1, 128.2, 126.9, 124.6, 123.4, 117.5, 113.1, 110.9, 52.2,
37.0, 35.5, 28.6; IR (KBr,
cmꢁ1): 3315, 1656, 1596, 1557, 1495, 1442,
d 194.9, 143.2, 141.7, 136.0, 134.2, 131.0, 130.7,
amino)-6,6-dimethyl-6,7-dihydro-1H-indol-4(5H)-one (4o). A white
solid; mp: 153e154 ꢀC; 1H NMR (400 MHz, CDCl3)
d
7.53 (d,
n
J¼6.4 Hz, 2H, ArH), 7.11e6.80 (m, 9H, ArH, 8H and NH, 1H), 6.50 (d,
1408, 1310, 1169, 1111, 1088, 1040, 816, 772, 702; HRMS (ESI): m/z
calcd for C28H23ClBrN2O, 519.0657 [MꢁH]ꢁ, found: 519.0695.
J¼7.2 Hz, 2H, ArH), 2.49 (s, 2H, CH2), 2.38 (s, 2H, CH2), 1.10 (s, 6H,
CH3) 13C NMR (100 MHz, CDCl3)
d 195.0, 142.3, 136.3, 132.7, 132.6,
130.1, 129.5, 129.2, 128.3, 124.1, 122.4, 117.3, 113.0, 52.1, 37.0, 35.5,
4.1.21. 1-(4-Chlorophenyl)-6,6-dimethyl-3-((4-nitrophenyl)amino)-
28.6; IR (KBr,
n
cmꢁ1): 3291, 2956, 1642, 1584, 1540, 1491, 1443,
2-phenyl-6,7-dihydro-1H-indol-4(5H)-one (4u). A white solid; mp:
1422, 1396, 1310, 1094, 1011, 829, 817; HRMS (ESI): m/z calcd for
C28H22Cl2BrN2O, 553.0266 [MꢁH]ꢁ, found: 553.0290.
209e210 ꢀC; 1H NMR (400 MHz, CDCl3)
d
7.84 (d, J¼9.2 Hz, 2H,
ArH), 7.42e7.38 (m, 3H, ArH, 2H and NH, 1H), 7.14e7.12 (m, 2H,
ArH), 7.08e7.06 (m, 3H, ArH), 6.98e6.96 (m, 2H, ArH), 6.54 (d,
J¼9.2 Hz, 2H, ArH), 2.54 (s, 2H, CH2), 2.40 (s, 2H, CH2), 1.12 (s, 6H,
4.1.16. 1-(4-Bromophenyl)-3-((4-bromophenyl)amino)-2-(4-
chlorophenyl)-6,6-dimethyl-6,7-dihydro-1H-indol-4(5H)-one (4p). A
CH3) 13C NMR (100 MHz, CDCl3)
d 194.8, 139.1, 137.0, 130.4, 129.4,
white solid; mp: 188e189 ꢀC; 1H NMR (400 MHz, CDCl3)
d
7.53 (d,
129.1, 128.6, 128.3, 128.0, 127.4, 125.3, 121.5, 113.8, 52.2, 36.9, 35.6,
J¼7.2 Hz, 2H, ArH), 7.12- 6.94 (m, 7H, ArH, 6H and Nh, 1H), 6.86 (d,
28.6; IR (KBr,
n
cmꢁ1): 3304, 2962, 1650, 1593, 1555, 1534, 1492,
J¼7.6 Hz, 2H, ArH), 6.45 (d, J¼7.6 Hz, 2H, ArH), 2.49 (s, 2H, CH2), 2.38
1455, 1404, 1321, 1277, 1110, 1049, 832, 751, 712; HRMS (ESI): m/z
calcd for C28H25ClN3O3, 486.1584 [MþH]þ, found: 486.1595.
(s, 2H, CH2), 1.10 (s, 6H, CH3) 13C NMR (100 MHz, CDCl3)
d 195.0,
142.9, 142.0, 136.2, 132.7, 131.2, 130.1, 129.5, 129.2, 128.4, 125.1,
122.4, 122.0, 117.6, 113.0, 111.3, 52.1, 36.9, 35.5, 28.6; IR (KBr,
n
4.1.22. 1-(4-Chlorophenyl)-3-((3,4-dichlorophenyl)amino)-6,6-
cmꢁ1): 3334, 2956, 1640, 1587, 1529, 1488, 1453, 1392, 1309, 1240,
1114, 1092, 1070, 1012, 812; HRMS (ESI): m/z calcd for
C28H22Br2ClN2O, 596.9762 [MꢁH]ꢁ, found: 596.9788.
dimethyl-2-phenyl-6,7-dihydro-1H-indol-4(5H)-one (4v). A white
solid; mp: 213e213.2 ꢀC; 1H NMR (400 MHz, CDCl3)
d 7.35 (d,
J¼8.6 Hz, 2H, ArH), 7.08e7.05 (m, 5H, ArH, 4H and NH, 1H),
6.99e6.89 (m, 4H, ArH), 6.60 (d, J¼2.8 Hz, 1H, ArH), 6.47e6.44 (m,
1H, ArH), 2.51 (s, 2H, CH2), 2.39 (s, 2H, CH2), 1.11 (s, 6H, CH3) 13C
4.1.17. 2-(4-Bromophenyl)-3-((4-chlorophenyl)amino)-6,6-dimethyl-
1-phenyl-6,7-dihydro-1H-indol-4(5H)-one (4q). A white solid; mp:
NMR (100 MHz, CDCl3)
130.5, 129.7, 129.5, 129.2, 129.1, 128.3, 127.2, 123.9, 123.7, 121.4, 117.1,
115.5, 113.0, 52.2, 37.0, 35.6, 28.6; IR (KBr,
cmꢁ1): 3299, 2957, 1643,
d 195.0, 143.7, 141.8, 135.8, 134.3, 131.9,
204e204.4 ꢀC; 1H NMR (400 MHz, CDCl3)
d 7.40 (s, 3H, ArH, 2H and
NH), 7.16e7.10 (m, 4H, ArH), 6.90 (d, J¼8.4 Hz, 2H, ArH), 6.81 (d,
n
J¼8.4 Hz, 2H, ArH), 6.52 (d, J¼8.4 Hz, 2H, ArH), 2.49 (s, 2H, CH2),
1577, 1467, 1400, 1311, 1129, 1047, 831, 763; HRMS (ESI): m/z calcd
2.38 (s, 2H, CH2),1.10 (s, 6H, CH3) 13C NMR (100 MHz, CDCl3)
d 194.9,
for C28H22Cl3N2O, 509.0767 [MꢁH]ꢁ, found: 509.0774.
142.6, 137.2, 131.1, 130.3, 130.0, 129.5, 128.5, 128.3, 128.0, 123.9,
120.6, 117.1, 52.2, 36.9, 35.5, 28.6; IR (KBr,
n
cmꢁ1): 3316, 2955, 1660,
4.1.23. 1-(4-Bromophenyl)-3-((4-chlorophenyl)amino)-6,6-dimethyl-
1596, 1569, 1553, 1488, 1443, 1406, 1367, 1323, 1284, 1248, 1169,
1115, 1101, 832, 816, 719; HRMS (ESI): m/z calcd for C28H23ClBrN2O,
519.0657 [MꢁH]ꢁ, found: 519.0691.
2-phenyl-6,7-dihydro-1H-indol-4(5H)-one (4w). A white solid; mp:
172e173 ꢀC; 1H NMR (400 MHz, CDCl3)
d
7.50 (d, J¼7.6 Hz, 2H, ArH),
7.05 (s, 3H, ArH, 2H and NH, 1H), 6.99 (d, J¼7.6 Hz, 2H, ArH), 6.93 (d,
J¼4.8 Hz, 3H, ArH), 6.86 (d, J¼7.6 Hz, 2H, ArH), 6.50 (d, J¼7.6 Hz, 2H,
ArH), 2.50 (s, 2H, CH2), 2.38 (s, 2H, CH2), 1.11 (s, 6H, CH3) 13C NMR
4.1.18. 2-(4-Bromophenyl)-1-(4-chlorophenyl)-6,6-dimethyl-3-((4-
nitrophenyl)amino)-6,7-dihydro-1H-indol-4(5H)-one (4r). A white
(100 MHz, CDCl3)
129.1, 128.2, 128.1, 126.8, 124.8, 123.7, 123.2, 122.1, 117.1, 113.1, 52.2,
37.0, 35.5, 28.6; IR (KBr,
cmꢁ1): 3306, 2959, 1645, 1584, 1537, 1593,
d 195.0, 142.7, 141.6, 136.52, 132.5, 130.7, 129.5,
solid; mp: 208e209 ꢀC; 1H NMR (400 MHz, CDCl3)
d 7.89 (d,
J¼9.2 Hz, 2H, ArH), 7.49e7.37 (m, 3H, ArH, 2H and NH, 2H),
7.22e7.20 (m, 3H, ArH), 7.17e7.09 (m, 2H, ArH), 6.84 (d, J¼8.4 Hz,
2H, ArH), 6.55 (d, J¼9.2 Hz, 2H, ArH), 2.52 (s, 2H, CH2), 2.39 (s, 2H,
n
1447, 1397, 1307, 1072, 1012, 817, 762; HRMS (ESI): m/z calcd for
C28H23ClBrN2O, 519.0657 [MꢁH]ꢁ, found: 519.0688.
CH2), 1.11 (s, 6H, CH3); 13C NMR (100 MHz, CDCl3)
d 194.8, 150.1,
142.7, 139.4, 136.8, 131.6, 130.4, 129.6, 129.3, 128.8, 127.9, 125.5,
4.1.24. 1-(4-Bromophenyl)-6,6-dimethyl-3-((4-nitrophenyl)amino)-
124.9, 121.9, 121.5, 113.8, 113.4, 52.2, 36.9, 35.6, 28.6; IR (KBr,
n
2-phenyl-6,7-dihydro-1H-indol-4(5H)-one (4x). A white solid; mp:
cmꢁ1): 3301, 2945, 1663, 1599, 1526, 1489, 1448, 1367, 1325, 1306,
1274, 1113, 1013, 833, 753, 719; HRMS (ESI): m/z calcd for
C28H24ClBrN3O3, 566.0665 [MþH]þ, found: 566.0698.
209e210 ꢀC; 1H NMR (400 MHz, CDCl3)
d
7.84 (d, J¼9.2 Hz, 2H,
ArH), 7.53 (d, J¼8.4 Hz, 2H, ArH), 7.13e7.08 (m, 3H, ArH, 1H and NH,
1H), 7.02e6.95 (m, 5H, ArH), 6.52 (d, J¼9.2 Hz, 2H, ArH), 2.53 (s, 2H,
CH2), 2.40 (s, 2H, CH2), 1.22 (s, 6H, CH3) 13C NMR (100 MHz, CDCl3)
4.1.19. 3-((4-Bromophenyl)amino)-6,6-dimethyl-1,2-diphenyl-6,7-
d
194.7, 150.1, 142.1, 139.2, 136.1, 132.7, 130.1, 129.5, 129.1, 128.6,
127.6125.6, 125.3, 122.5, 121.8, 113.9, 113.5, 52.2, 36.9, 35.6, 28.6; IR
(KBr,
cmꢁ1): 3304, 2945, 1643, 1594, 1583, 1538, 1492, 1446, 1423,
dihydro-1H-indol-4(5H)-one (4s). A white solid; mp: 175e176 ꢀC;
1H NMR (400 MHz, CDCl3)
d
7.41e7.40 (m, 3H, ArH, 2H and NH,
n
1H), 7.19e7.11 (m, 2H, ArH), 7.06e7.05 (m, 5H, ArH), 7.01e6.93 (m,
1397, 1309, 1094, 1075, 833, 813, 762; HRMS (ESI): m/z calcd for
C28H23BrN3O3, 530.0901 [MꢁH]ꢁ, found: 530.0930.
2H, ArH), 2.54 (s, CH2, 2H), 2.41 (s, 2H, CH2), 1.13 (s, 6H, CH3) 13C
NMR (100 MHz, CDCl3)
131.0, 129.3, 129.1, 128.3, 128.0, 128.0, 126.7, 124.3, 123.7, 117.4,
112.9, 110.7, 52.3, 37.0, 35.5, 28.6; IR (KBr,
cmꢁ1): 3304, 2958,
1651, 1591, 1574, 1556, 1492, 1449, 1302, 1246, 1170, 1045, 811, 774;
d 194.9, 194.9, 143.5, 143.5, 141.8, 137.5,
4.1.25. 1-(4-Bromophenyl)-2-(4-chlorophenyl)-3-((4-chlorophenyl)
n
amino)-6,7-dihydro-1H-indol-4(5H)-one (4y). A white solid; mp:
226e228 ꢀC; 1H NMR (400 MHz, CDCl3)
d
7.53 (d, J¼7.6 Hz, 2H,

2946
Y. Li et al. / Tetrahedron 69 (2013) 2941e2946
4315e4317; (f) Gajare, A. S.; Toyota, K.; Yoshifuji, M.; Yoshifuji, F. Chem. Com-
mun. 2004, 1994e1995; (g) Ma, D.; Zhang, Y.; Yao, J.; Wu, S.; Tao, F. J. Am. Chem.
Soc. 1998, 120, 12459e12467; (h) Ma, D.; Cai, Q.; Zhang, H. Org. Lett. 2003, 5,
2453e2455; (i) Zhu, L.; Cheng, L.; Zhang, Y.; Xie, R.; You, J. J. Org. Chem. 2007, 72,
2737e2743.
5. For reviews on Pd-catalyzed N-arylations, see: (a) Hartwig, J. F. Angew. Chem.,
Int. Ed. 1998, 37, 2046e2067; (b) Wolfe, J. P.; Wagaw, S.; Marcoux, J.-F.;
Buchwald, S. L. Acc. Chem. Res. 1998, 31, 805e818; (c) Muci, A. R.; Buchwald, S. L.
Topics in Current Chemistry; Springer GmbH: Germany, 2002; Vol. 219, Chapter
5; (d) Yang, B. H.; Buchwald, S. L. J. Organomet. Chem. 1999, 576, 125e133; (e)
Hartwig, J. F. Acc. Chem. Res. 1998, 31, 852e860.
ArH), 7.05e6.99 (m, 4H, ArH), 6.90e6.85 (m, 4H, ArH), 6.51 (d,
J¼8.0 Hz, 2H, ArH), 2.66e2.63 (m, 2H, CH2), 2.53e2.50 (m, 2H, CH2),
2.20e2.03 (m, 2H, CH2); IR (KBr,
n
cmꢁ1): 3353, 3056, 1636, 1588,
1504, 1444, 1396, 1253, 1020, 821; HRMS (ESI): m/z calcd for
C26H19BrCl2N2O, 548.9928 [MþNa]þ, found: 548.9959.
4.1.26. 1,2-Bis(4-bromophenyl)-3-((4-chlorophenyl)amino)-6,7-
dihydro-1H-indol-4(5H)-one (4z). A white solid; mp: 194e196 ꢀC;
1H NMR (400 MHz, CDCl3)
d
7.50 (d, J¼7.6 Hz, 2H, ArH), 7.01 (d,
6. (a) Pyrroles, The Synthesis, Reactivity, and Physical Properties of Substituted Pyr-
roles, Part II; Jones, R. A., Ed.; Wiley: New York, NY, 1992; (b) Jacobi, P. A.; Coults,
L. D.; Guo, J. S.; Leung, S. I. J. Org. Chem. 2000, 65, 205e213; (c) Furstner, A.
J¼7.6 Hz, 2H, ArH), 6.90e6.81 (m, 6H, ArH), 6.53 (d, J¼8.0 Hz, 2H,
ArH), 2.66e2.64 (m, 2H, CH2), 2.53e2.50 (m, 2H, CH2), 2.22 (s, 3H,
€
Angew. Chem., Int. Ed. 2003, 42, 3528e3603; (d) Furstner, A.; Szillat, H.; Gabor,
CH3), 2.17e2.06 (m, 2H, CH2); IR (KBr,
n
cmꢁ1): 3353, 1651, 1598,
B.; Mynott, R. J. Am. Chem. Soc. 1998, 120, 8305e8314; (e) Jones, R. A.; Bean, G. P.
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1523, 1488, 1446, 1396, 1070, 1010, 824; HRMS (ESI): m/z calcd for
C27H22BrClN2O, 529.0477 [MþNa]þ, found: 529.0493.
4.1.27. 1,2-Bis(4-bromophenyl)-3-((4-chlorophenyl)amino)-6,7-dihy-
8. Schwier, T.; Sromek, A. W.; Yap, D. M. L.; Chernyak, D.; Gevorgyan, V. J. Am.
Chem. Soc. 2007, 129, 9868e9878.
dro-1H-indol-4(5H)-one (4aa). A white solid; mp: 223e224 ꢀC; 1H
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NMR (400 MHz, CDCl3)
d
7.53 (d, J¼7.2 Hz, 2H, ArH), 7.19 (d,
J¼7.2 Hz, 2H, ArH), 7.00 (d, J¼7.6 Hz, 2H, ArH), 6.90 (d, J¼7.6 Hz, 2H,
ArH), 6.79 (d, J¼7.6 Hz, 2H, ArH), 6.51 (d, J¼8.0 Hz, 2H, ArH),
2.65e2.64 (m, 2H, CH2), 2.53e2.50 (m, 2H, CH2), 2.23e2.07 (m, 2H,
CH2); IR (KBr,
n
cmꢁ1): 3351, 3054, 2946, 2360, 1651, 1558, 1457,
1421, 1093, 1013, 825; HRMS (ESI): m/z calcd for C26H19Br2ClN2O,
570.9605 [MþH]þ, found: 570.9563.
Acknowledgements
We are grateful for financial support from the National Science
Foundation of China (21072163, 21232004, 21272095, and
21102124), PAPD of Jiangsu Higher Education Institutions, the NSF
of Jiangsu Education Committee (11KJB150016), Jiangsu Science
and Technology Support Program (No. BE2011045), the Qing Lan
Project (12QLG006), and Doctoral Research Foundation of Xuzhou
Normal Univ. (XZNU, No. 10XLR20).
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Supplementary data
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Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.tet.2013.02.026.
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References and notes
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(d) Goldberg, I. Ber. Dtsch. Chem. Ges. 1906, 39, 1691e1692.
3. For recent reviews on Cu-catalyzed N-arylations, see: (a) Sawyer, J. S. Tetrahedron
2000, 56, 5045e5065; (b) Kunz, K.; Scholz, U.; Ganzer, D. Synlett 2003,
2428e2439; (c) Ley, S. V.; Thomas, A. W. Angew. Chem., Int. Ed. 2003, 42,
5400e5449; (d) Beletskaya, I. P.; Cheprakov, A. V. Coord. Chem. Rev. 2004, 248,
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2011, 745e769 and references cited therein.
Mechanisms, and Structure, 6th ed.; John Wiley & Sons: Hoboken, NJ, 2007;
€
pp 380e382; (b) Brown, H. C.; McDaniel, D. H.; Haflinger, O. In Determination of
Organic Structures by Physical Methods; Braude, E. A., Nachod, F. C., Eds.; Aca-
demic: New York, NY, 1955; Vol. 1, pp 567e662.
ꢀ
16. (a) Perio, B.; Dozias, M. J.; Jacquault, P.; Hamelin, J. Tetrahedron Lett. 1997, 38,
ꢀ
ꢀ
7867e7870; (b) Goncalo, P.; Roussel, C. J.; Melot, M.; Vebrel, J. J. Chem. Soc.,
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17. Crystal data for 4h (CCDC-921882): C29H27N3O4, crystal dimension 0.45ꢂ0.
4. For selected papers on Cu-catalyzed N-arylations: (a) Klapars, A.; Antilla, J. C.;
Huang, X.; Buchwald, S. L. J. Am. Chem. Soc. 2001, 123, 7727e7729; (b) Klapars,
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21ꢂ0.18 mm, Triclinic, space group P-1, a¼6.1780(5), b¼12.9104(11), c¼16.
0678(13),
a
¼100.437(2)ꢀ,
b
¼100.398(2)ꢀ,
g
¼91.4430(10)ꢀ, V¼1237.45(18)3,
Mr¼481.54, Z¼2, Dc¼1.292 Mg/m3,
l
¼0.71073,
m
(Mo Ka)¼0.087 mmꢁ1, F(000)¼
508, R¼0.0593, wR2¼0.1348, S¼1.032, largest diff. peak and hole: 0.235 and ꢁ0.
3
ꢁ
245 e/A .