Efficient synthesis of pentasubstituted pyrroles via one-pot reactions of arylamines, acetylenedicarboxylates, and 3-phenacylideneoxindoles

Article abstract of DOI:10.1016/j.tet.2012.07.056

An efficient synthetic method for the pentasubstituted pyrroles was successfully developed via the one-pot domino reactions of arylamines, acetylenedicarboxylates, and 3-phenacylideneoxindoles. The reaction mechanism involved the sequential Michael additi

Full text of DOI:10.1016/j.tet.2012.07.056

Tetrahedron 68 (2012) 8256e8260
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Efficient synthesis of pentasubstituted pyrroles via one-pot reactions of
arylamines, acetylenedicarboxylates, and 3-phenacylideneoxindoles
*
Ying Han, Yan Sun, Jing Sun, Chao-Guo Yan
College of Chemistry & Chemical Engineering, Yangzhou University, Yangzhou 225002, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 8 April 2012
Received in revised form 13 July 2012
Accepted 17 July 2012
Available online 21 July 2012
An efficient synthetic method for the pentasubstituted pyrroles was successfully developed via the one-
pot domino reactions of arylamines, acetylenedicarboxylates, and 3-phenacylideneoxindoles. The re-
action mechanism involved the sequential Michael addition and ring closure of the in situ generated
active enamino ester.
b-
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
One-pot reaction
Domino reaction
Heterocycle
Pyrrole
Isatin
Electron-deficient alkyne
1. Introduction
nitrostyrene.20 Very recently, Jiang reported three-component
reactions of aromatic aldehydes, arylamines, and acetylenedi-
carboxylates to give 3-arylamino-2-pyrrolidinones.21 We found
that this three-component reaction under acid catalyst afforded
novel 3-hydroxy-2-pyrrolidinones.22 Despite numerous diverse
approaches toward the synthesis of pyrroles have been developed so
far, the development of new and efficient methods for their synthesis
remains an area of current interest. As part of our current studies on
investigation of the versatile reactivity of electron-deficient alkynes
and the design of new routes for the preparation of biologically active
heterocyclic compounds,23 Here we wish to report an efficient syn-
thetic method for the functionalized pyrroles containing 3-isatinyl
group from the one-pot domino reactions of arylamines, acetylene-
dicarboxylates, and 3-phenacylideneoxindoles.
The pyrrole ring is widely present in numerous natural products,
synthetic pharmaceuticals, and molecular metarials.1,2 Therefore,
considerable attention has beenpaid to develop efficient methods for
the synthesis of these privileged molecules. Classical methods for the
synthesis of polysubstituted pyrroles included Knorr reaction,
Hantzsch reaction, and PaaleKnorr condensation reaction.3,4
Recently, new approaches based on the multicomponent reactions
and cycloisomerizations have drawn extensive and enduring
attentions.5e8 The multicomponent reactions containing active
Huisgen’s 1,4-dipoles, which were formed in situ from the addition of
nucleophiles to electron-deficient alkynes, have become one of the
most efficient methods for preparation of diverse substituted pyr-
roles. As for some examples, these reactions are included the Huis-
gen’s 1,4-dipoles derived from additions of alkyl(aryl) isocyanides to
dimethyl acetylenedicarboxylate are trapped by succinimide,9
cyclobutene-1,2-diones,10 and benzoyl chloride.11 Triarylphosphine
induced domino reactions of acetylenedicarboxylates with some
unsaturated compounds12e15 and tertiary amines as well as other
catalyst assisted domino reactions16e18 are also efficient synthetic
methods for the functionalized pyrroles. The new approaches toward
the syntheses of polysubstituted pyrroles are FeCl3 catalyzed three-
component reactions of amines, DMAD, and phenacyl bromide19 or
2. Results and discussions
According to our previously established procedure for the
preparation of 3-hydroxy-2-pyrrolidinones by three-component
reactions, firstly p-methylaniline reacted with dimethyl acetyle-
nedicarboxylate in ethanol to give the active
3-p-chlorophenacylideneoxindole was added to the solution of
-enamino ester, but no reaction was observed both at room or at
b-enamino ester. Then
b
reflux temperature. Then we tried various Lewis acids as catalyst for
his reaction and found that iodine and ferric trichloride showed
some catalytic activity. The best result was obtained by using acetic
acid both as catalyst and solvent. Thus p-methylaniline firstly
* Corresponding author. E-mail address: cgyan@yzu.edu.cn (C.-G. Yan).
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2012.07.056

Y. Han et al. / Tetrahedron 68 (2012) 8256e8260
8257
reacted with dimethyl acetylenedicarboxylate in acetic acid at
room temperature for the formation of an active -enamino ester.
b
Then an equal molar of 3-p-chlorophenacylideneoxindole was
added, and the reaction proceeded smoothly in refluxing acetic acid
for 24 h to give the desired pentasubstituted pyrrole 4a in good
yield (74%, Table 1, entry 1). Then various amines and
3-phenacylideneoxindoles with different substituents were uti-
lized under the same reaction conditions. From the results shown
in Table 1, we could see that all of the reactions proceeded smoothly
to afford the corresponding pentasubstituted pyrroles 4be4k in
satisfactory yields (Table 1, entries 2e11). Arylamines with
electron-donating methyl, methoxyl groups and weak electron-
withdrawing chloro groups reacted efficiently to yield the desired
products. The reaction of benzylamine,
a-phenylethylamine, and
b
-phenylamines also resulted in high yields of the pentasubstituted
pyrroles 4le4m (Table 1, entries 12e14). Diethyl acetylenedi-
carboxylate could also be successfully used in the reaction (Table 1,
entries 16 and 17). The structures of the polysubstituted pyrroles
were fully characterized by 1H and 13C NMR, HRMS, IR spectra, and
the structure of compound 4e was further confirmed by single-
crystal X-ray diffraction studies (Fig. 1).
Fig. 1. Molecular structure of polysubstituted pyrrole 4e.
Table 1
Synthesis of pentasubstituted pyrroles via domino reactionsa
H
N
O
Ar'
CO R
2
RO
C
2
O
O
R'
HO Ac
reflux
ArNH
+
+
2
R'
Ar'
N
RO C
CO R
N
2
2
H
Ar
Entry
Compd
Ar
Ar0
R
R0
Yieldb (%)
1
2
3
4
5
6
7
8
4a
4b
4c
4d
4e
4f
4g
4h
4i
4j
4k
4l
4m
4n
4o
4p
4q
p-CH3C6H4
p-ClC6H4
p-ClC6H4
p-CH3C6H4
C6H5
CH3
H
CH3
F
CH3
CH3
Cl
74
85
83
78
80
87
88
76
81
75
72
82
85
81
89c
77
79
p-CH3OC6H4
p-CH3OC6H4
p-CH3C6H4
p-CH3C6H4
p-CH3C6H4
p-CH3C6H4
p-CH3C6H4
p-(CH3)3CC6H4
C6H5
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
p-ClC6H4
p-CH3OC6H4
p-CH3C6H4
C6H5
p-ClC6H4
p-CH3OC6H4
p-ClC6H4
Cl
Cl
9
CH3
Cl
CH3
CH3
Cl
F
Cl
Cl
Cl
10
11
12
13
14
15
16
17
p-ClC6H4
C6H5CH2
p-ClC6H4
C6H5(CH3)CH
C6H5CH2CH2
p-CH3C6H4
p-CH3OC6H4
p-CH3C6H4
p-CH3C6H4
p-CH3C6H4
p-CH3C6H4
p-CH3OC6H4
p-CH3C6H4
CH3CH2
CH3CH2
a
Reactions were performed with arylamine (2.2 mmol), acetylenedicarboxylate (2.2 mmol) in acetic acid (10.0 mL), rt, 12 h; then 3-phenacylideneoxindoles (2.0 mmol),
reflux, 24 h.
b
c
Isolated yields based on 3-phenacylideneoxindole.
1-Benzyl-5-chloro-3-p-methylphenacylideneoxindole was used.
The efficient preparation of the functionalized pyrroles con-
Michael addition of b-enamino ester (A) to the exocyclic carbon
taining 3-isatinyl group by this three-component reaction is very
interesting. First, despite numerous diverse approaches toward the
syntheses of polysubstituted pyrroles with various substituents
have been furnished, only a few reports on the synthesis of isatinyl
pyrroles were documented in literature.24e26 Secondly it is unusual
to obtain the isatinyl substituted products from the reactions of
3-phenacylideneoxindoles since the reactions of isatin and
3-isatinylidene compounds usually gave the spirocyclic oxin-
doles27,28 To explain the mechanism of this one-pot three-compo-
nent reaction, a plausible reaction course was proposed based on
the previously reported reactions, which is illustrated in Scheme 1.
atom of 3-phenacylideneoxindole gives the intermediate (B).
Thirdly the intramolecular nucleophilic addition of amino group to
carbonyl group in adduct (B) produces a cyclic intermediate (C). At
last the dehydration of (C) yields the final isatinyl substituted
pyrroles 4. If
b-enamino ester (A) attacks the carbon atom at
3-position of 3-phenacylideneoxindole, another kind of adduct (D)
would be formed and through its further reactions spiro[oxindole-
3,40-pyridine] derivatives might be finally produced. It might be
due to more steric hindrance at 3-position of oxindole, the selective
reaction of
b-enamino ester at exocyclic carbon atom gives the
desired oxindole substituted pyrrole derivatives.
The first reaction is the formation of active
the addition of arylamine to acetylenedicarboxylate. Secondly
b
-enamino ester (A) by
In conclusion, we have described a one-pot domino reaction of
arylamines, acetylenedicarboxylate, phenacylideneoxindoles and

8258
Y. Han et al. / Tetrahedron 68 (2012) 8256e8260
Ar'
O
HN
CO R
2
O
O
RO
RO
C
C
2
2
Ar'
HO Ac
N
3
ArNH
+
H
2
RO C
2
O
NH
Ar
CO R
2
RO C
N Ar
2
H
1
2
(A)
(B)
H
N
H
N
O
O
HN
_
RO C
RO C
O
H O
2
2
2
Ar'
RO
C
Ar'
OH
2
O
RO
C
Ar'
RO
C
N
2
N
2
RO
C
HN Ar
2
Ar
Ar
4
(C)
(D)
Scheme 1. The proposed formation mechanism of the polysubstituted pyrroles.
found an efficient procedure for the synthesis of polysubstituted
pyrroles, especially with an isatinyl group as substituent. The
reaction mechanism was briefly discussed. Prominent among the
advantages of this new method are operational simplicity, good
yields of products in short reaction times, and easy work-up pro-
cedures. Further expansion of the reaction scope and synthetic
applications of this methodology are in progress in our laboratory.
1618, 1561, 1514, 1473, 1446, 1359, 1332, 1293, 1250, 1231, 1201, 1170,
1131, 1087, 1038,1017, 978, 952, 891, 833, 782 cmꢁ1; MS (m/z): HRMS
(ESI) calcd for C29H22ClN2O5 ([MꢁH]ꢁ): 513.1223. Found: 513.1216.
3.2.2. Compound 4b. White solid, 85%, mp 280e282 ꢀC; 1H NMR
(600 MHz, DMSO-d6) d: 10.31 (s,1H, NH), 7.35 (br s, 3H, ArH), 7.19 (br
s, 2H, ArH), 6.95e6.82 (m, 5H, ArH), 6.68 (br s,1H, ArH), 4.30 (br s,1H,
CH), 3.73 (s, 3H, OCH3), 3.58 (s, 3H, OCH3), 3.35 (s, 3H, OCH3), 2.20 (s,
3H, CH3); 13C NMR (150 MHz, DMSO-d6)
d
: 161.0, 158.9, 140.3, 133.4,
132.6,129.9,129.8,129.4,129.3,129.2,128.1,128.0,127.8,124.2,116.6,
113.7, 109.0, 108.6, 55.2, 52.2, 51.0, 50.8, 20.6; IR (KBr) : 3178, 3078,
3. Experimental section
3.1. General
n
3039, 2999, 2945, 2918, 2839, 1702, 1626, 1608, 1556, 1512, 1484,
1448, 1400, 1364, 1325, 1298, 1247, 1204, 1173, 1139, 1287, 1033, 977,
953, 883, 838, 805, 780 cmꢁ1; MS (m/z): HRMS (ESI) calcd for
C30H24N2O6 ([MꢁH]ꢁ): 543.1328. Found: 543.132.
All reagents and solvents were commercial available with ana-
lytical grade and used as received. Evaporation removal of organic
solvents was carried out with a rotary evaporator in conjunction
with a water aspirator. Melting points were taken on a hot-plate
microscope apparatus and were uncorrected. 1H and 13C NMR
spectra were recorded on a Bruker AV-600 instrument. IR spectra
were obtained on a Bruker Tensor27 spectrometer (KBr disc). HRMS
were measured at AB 5800 MALDI-TOF/TOF instrument. X-ray data
were collected on a Bruker Smart APEX-2 diffractometer.
3.2.3. Compound 4c. White solid, 83%, mp 271e274 ꢀC; 1H NMR
(600 MHz, DMSO-d6) d: 10.42 (s, 1H, NH), 7.18e7.09 (m, 5H, ArH),
6.98e6.77 (m, 6H, ArH), 4.35 (br s,1H, CH), 3.73 (s, 3H, OCH3), 3.57 (s,
3H, OCH3), 3.33 (s, 3H, OCH3), 2.22 (s, 3H, CH3); 13C NMR (150 MHz,
DMSO-d6)
130.8, 130.7, 129.6, 129.2, 128.8, 127.8, 126.2, 115.5, 113.7, 113.5, 111.3,
109.4, 109.3, 55.2, 52.2, 44.6, 20.7; IR (KBr) : 3175, 3132, 3082, 3052,
d: 177.3, 161.1, 158.8, 157.0, 139.0, 137.9, 131.8, 131.7, 130.9,
n
3.2. General procedure for the one-pot reactions of aryl-
amines, acetylenedicarboxylate, and 3-
phenacylideneoxindoles
2995, 2950, 2883,1734,1709,1630,1562,1484,1450,1364,1296,1245,
1191, 1139, 973, 952, 889, 848, 828, 809, 778 cmꢁ1; MS (m/z): HRMS
(ESI) calcd for C30H24FN2O6 ([MꢁH]ꢁ): 527.1624. Found: 527.1616.
A mixture of an arylamine (2.2 mmol) and acetylenedicarbox-
ylate (2.2 mmol) in 10.0 mL acetic acid was stirred at room tem-
perature overnight. Then 3-phenacylideneoxindoles (2.0 mmol)
were added. The reaction mixture was refluxed for about 1 day.
After adding some water (30 mL), the resulting precipitate was
collected by filtration and washed with a small portion of cold
ethanol to give the crude product, which was recrystallized in
ethanol to give pure product for analysis.
3.2.4. Compound 4d. White solid, 78%, mp 267e268 ꢀC; 1H NMR
(600 MHz, DMSO-d6) d: 10.31 (s, 1H, NH), 7.27e7.12 (m, 9H, ArH),
6.94 (d, J¼7.2 Hz,1H, ArH), 6.82 (s,1H, ArH), 6.68 (s,1H, ArH), 4.29 (br
s,1H, CH), 3.57 (s, 3H, OCH3), 3.32(s, 3H, OCH3), 2.26 (s, 3H, CH3), 2.20
(s, 3H, CH3); 13C NMR (150 MHz, DMSO-d6)
d
: 177.4, 163.4, 161.1,
140.3,138.0,134.4,130.9,130.8,129.9,129.1,128.5,128.1,127.7,124.0,
116.4, 116.3, 108.6, 52.2, 50.7, 44.2, 44.0, 20.6, 20.5; IR (KBr) : 3169,
n
3042, 2946, 2921, 2865, 1700, 1628, 1558, 1514, 1489, 1449, 1402,
1360, 1320, 1290, 1251, 1202, 1177, 1138, 1111, 1089, 1040, 1021, 977,
931, 885, 843, 809, 789, 764 cmꢁ1; MS (m/z): HRMS (ESI) calcd for
C30H25N2O5 ([MꢁH]ꢁ): 493.1769. Found: 493.1763.
3.2.1. Compound 4a. White solid, 74%, mp 258e260 ꢀC; 1H NMR
(600 MHz, DMSO-d6) d: 10.45 (s, 1H, NH), 7.37 (br s, 3H, ArH),
7.14e7.00 (m, 7H, ArH), 6.88e6.81 (m, 2H, ArH), 4.36 (br s, 1H, CH),
3.57 (s, 3H, OCH3), 3.34 (s, 3H, OCH3), 2.27 (s, 3H, CH3); 13C NMR
3.2.5. Compound 4e. White solid, 80%, mp 286e287 ꢀC; 1H NMR
(150 MHz, DMSO-d6)
132.6, 129.7, 129.2, 128.2, 128.1, 128.0, 127.7, 127.6, 123.4, 121.0, 116.6,
108.9, 52.2, 50.9, 43.9, 20.5; IR (KBr) : 3190, 3083, 2947, 2885, 1710,
d: 177.2, 163.3, 160.9, 142.7, 138.1, 134.2, 133.4,
(600 MHz, DMSO-d6)
d: 10.32 (s,1H, NH), 7.35 (br s, 3H, ArH), 7.14 (br
s, 5H, ArH), 6.94 (d, J¼7.2 Hz,1H, ArH), 6.82 (s,1H, ArH), 6.68 (br s,1H,
n

Y. Han et al. / Tetrahedron 68 (2012) 8256e8260
8259
ArH), 4.35 (br s,1H, CH), 3.58 (s, 3H, OCH3), 3.33 (s, 3H, OCH3), 2.27 (s,
3H, CH3), 2.20 (s, 3H, CH3); 13C NMR (150 MHz, DMSO-d6)
: 177.3,
177.2,163.4,161.0,140.3,138.2,134.2,133.4,132.6,132.4,129.9,129.8,
129.2, 128.8, 128.2, 128.1, 128.0, 127.8, 127.7, 124.1, 116.8, 116.7, 116.6,
920, 886, 841, 814, 787 cmꢁ1; MS (m/z): HRMS (ESI) calcd for
C29H22ClN2O6 ([MꢁH]ꢁ): 529.1172. Found: 529.1163.
d
3.2.11. Compound 4k. White solid, 72%, mp 297e299 ꢀC; 1H NMR
108.7, 52.2, 50.9, 43.9, 20.6; IR (KBr) n: 3189, 3081, 3033, 2945,1920,
(600 MHz, DMSO-d6)
d
: 10.32 (s, 1H, NH), 7.42 (d, J¼7.2 Hz, 3H,
2865,1701,1625,1558,1154,1483,1447,1363,1325,1294,1253,1204,
1177, 1139, 1088, 1039, 1018, 979, 953, 880, 832, 807, 778 cmꢁ1; MS
(m/z): HRMS (ESI) calcd for C30H24ClN2O5 ([MꢁH]ꢁ): 527.1371.
Found: 527.1374.
ArH), 7.33e7.32 (m, 5H, ArH), 6.95 (d, J¼7.8 Hz, 1H, ArH), 6.83 (s,
1H, ArH), 6.68 (br s, 1H, ArH), 4.40 (br s, 1H, CH), 3.59 (s, 3H,
OCH3), 3.33 (s, 3H, OCH3), 2.20 (s, 3H, CH3); 13C NMR (150 MHz,
DMSO-d6) d: 177.7, 161.0, 160.1, 140.8, 140.6, 139.1, 137.6, 136.4,
134.1, 133.8, 133.7, 133.2, 133.0, 132.9, 131.0, 130.8, 130.5, 130.4,
130.0, 129.2, 128.8, 128.6, 128.5, 128.4, 128.3, 126.9, 125.6, 124.8,
123.7, 119.7, 117.4, 109.6, 109.2, 52.7, 51.6, 44.7, 44.3, 21.1; IR (KBr) n:
3084, 3035, 2945, 1703, 1626, 1557, 1523, 1491, 1446, 1397, 1361,
1324, 1295, 1253, 1239, 1203, 1139, 1085, 1037, 1014, 978, 952, 850,
833, 805 cmꢁ1; MS (m/z): HRMS (ESI) calcd for C29H21Cl2N2O5
([MꢁH]ꢁ): 547.0833. Found: 547.0825.
3.2.6. Compound 4f. White solid, 87%, mp 259e260 ꢀC; 1H NMR
(600 MHz, DMSO-d6) d: 10.53 (s, 1H, NH), 7.20e7.06 (m, 8H, ArH),
6.81 (br s, 3H, ArH), 4.35 (br s, 1H, CH), 3.68 (s, 3H, OCH3), 3.57 (s,
3H, OCH3), 3.33 (s, 3H, OCH3), 2.27 (s, 3H, CH3); 13C NMR (150 MHz,
DMSO-d6)
129.1, 127.7, 127.3, 125.1, 123.4, 123.3, 121.0, 115.6, 113.6, 110.2, 54.9,
52.2, 50.9, 50.8, 50.7, 44.3, 20.5; IR (KBr) : 3191, 3118, 3048, 2946,
d: 177.2, 161.2, 159.2, 141.7, 138.0, 134.5, 132.3, 132.2,
n
2863, 1712, 1616, 1565, 1498, 1477, 1446, 1408, 1362, 1293, 1250,
1204, 1173, 1131, 1112, 1089, 1039, 974, 951, 927, 885, 837, 811,
790 cmꢁ1; MS (m/z): HRMS (ESI) calcd for C30H24ClN2O6 ([MꢁH]ꢁ):
543.1315. Found: 543.1322.
3.2.12. Compound 4l. White solid, 82%, mp 206e208 ꢀC; 1H NMR
(600 MHz, CDCl3) d: 8.82 (s,1H, NH), 7.24e7.16 (m, 7H, ArH), 6.94 (d,
J¼7.8 Hz, 1H, ArH), 6.85 (br s, 3H, ArH), 6.70 (br s, 1H, ArH), 5.32 (s,
2H, CH2), 4.42 (br s, 1H, CH), 3.70 (s, 3H, OCH3), 3.37 (s, 3H, OCH3),
2.25 (s, 3H, CH3); 13C NMR (150 MHz, CDCl3)
d
: 178.8, 164.7, 161.4,
139.0, 137.4, 135.5, 131.7, 128.6, 128.2, 127.7, 127.4, 126.1, 124.9, 124.2,
120.3, 109.2, 52.1, 51.5, 49.7, 44.4, 21.1; IR (KBr) : 3197, 3035, 2952,
1706, 1626, 1555, 1515,,1481, 1459, 1439, 1409, 1347, 1317, 1286,
3.2.7. Compound 4g. White solid, 88%, mp 274e276 ꢀC; 1H NMR
(600 MHz, DMSO-d6)
d: 10.53 (s, 1H, NH), 7.20e7.04 (m, 10H,
n
ArH), 6.80 (br s, 1H, ArH), 4.37 (br s, 1H, CH), 3.57 (s, 3H, OCH3),
3.33 (s, 3H, OCH3), 2.27 (s, 3H, CH3), 2.22 (s, 3H, CH3); 13C NMR
1232, 1161, 1121,1095,1057,1016, 982, 947, 894, 836, 808, 768 cmꢁ1
;
(150 MHz, DMSO-d6)
130.8, 129.1, 128.8, 127.7, 127.4, 126.1, 125.1, 123.3, 115.5, 110.2,
52.2, 50.9, 44.2, 20.7, 20.6; IR (KBr) : 3170, 3040, 2948, 2861,
d: 177.1, 163.4, 161.2, 141.8, 138.0, 134.5, 132.1,
MS (m/z): HRMS (ESI) calcd for C30H24ClN2O5 ([MꢁH]ꢁ): 527.1379.
Found: 527.1372.
n
1711, 1619, 1562, 1514, 1477, 1451, 1403, 1369, 1291, 1252, 1204,
1170, 1131, 1087, 1038, 973, 952, 929, 883, 845, 817, 790 cmꢁ1; MS
(m/z): HRMS (ESI) calcd for C30H24N2O5 ([MꢁH]ꢁ): 527.1379.
Found: 527.1371.
3.2.13. Compound 4m. White solid, 85%, mp 256e257 ꢀC; 1H NMR
(600 MHz, DMSO-d6) d: 10.53 (s, 1H, NH), 7.31e7.27 (m, 6H, ArH),
7.15e7.02 (m, 4H, ArH), 6.91e6.78 (m, 2H, ArH), 5.39 (s, 1H, CH),
4.37e4.11 (m, 1H, CH), 3.36e3.29 (m, 6H, OCH3), 2.32 (s, 3H, CH3),
1.80 (d, J¼48.6 Hz, 3H, CH3); 13C NMR (150 MHz, DMSO-d6)
d:
3.2.8. Compound 4h. White solid, 76%, mp 276e278 ꢀC; 1H NMR
(600 MHz, DMSO-d6) d: 10.54 (s, 1H, NH), 7.28e7.13 (m, 10H, ArH),
177.0, 162.4, 162.3, 141.7, 139.5, 139.4, 138.9, 132.4, 132.1, 131.2,
131.1, 130.9, 129.3, 128.1, 127.4, 127.3, 127.2, 127.1, 126.6, 126.5,
126.4, 126.3, 125.0, 124.9, 123.0, 115.1, 110.1, 110.0, 56.0, 55.5, 52.1,
7.06 (s, 1H, ArH), 6.80 (br s, 1H, ArH), 4.37 (br s, 1H, CH), 3.58 (s,
3H, OCH3), 3.33 (s, 3H, OCH3), 2.30 (s, 3H, CH3); 13C NMR
52.0, 50.5, 50.4, 44.3, 20.8, 19.0, 18.9; IR (KBr) n: 3325, 3027, 2980,
(150 MHz, DMSO-d6)
133.5, 132.3, 130.5, 130.4, 129.9, 129.5, 129.1, 128.8, 126.5, 124.7,
116.9, 111.6, 53.7, 52.3, 45.6, 22.4, 21.9; IR (KBr) : 3160, 3058, 2945,
d: 178.5, 173.4, 162.5, 143.1, 139.4, 135.7,
2947, 1729, 1707, 1619, 1565, 1520, 1480, 1451, 1376, 1352, 1330,
1282, 1231, 1168, 1106, 1063, 968, 927, 885, 817, 788 cmꢁ1; MS (m/
z): HRMS (ESI) calcd for C31H26ClN2O5 ([MꢁH]ꢁ): 541.1536. Found:
541.1527.
n
2751, 1709, 1621, 1556, 1513, 1480, 1451, 1362, 1289, 1251, 1234,
1200, 1169, 1132, 1089, 1039, 1020, 975, 933, 883, 842, 812,
785 cmꢁ1
; MS (m/z): HRMS (ESI) calcd for C29H22ClN2O5
3.2.14. Compound 4n. White solid, 81%, mp 187e188 ꢀC; 1H NMR
(600 MHz, CDCl3) d: 8.50 (s, 1H, NH), 7.22e7.19 (m, 5H, ArH), 7.04
([MꢁH]ꢁ): 513.1223. Found: 513.1218.
(br s, 1H, ArH), 6.89e6.88 (m, 2H, ArH), 6.86e6.83 (m, 2H, ArH),
6.72 (br s, 2H, ArH), 4.44 (br s, 1H, CH), 4.30e4.28 (m, 2H, CH2), 3.84
(s, 3H, OCH3), 3.48 (s, 3H, OCH3), 2.87e2.82 (m, 2H, CH2), 2.36 (s,
3.2.9. Compound 4i. White solid, 81%, mp 266e268 ꢀC; 1H NMR
(600 MHz, DMSO-d6) d: 10.33 (s, 1H, NH), 7.37e7.18 (m, 8H, ArH),
6.94 (d, J¼7.2 Hz, 1H, ArH), 6.81 (s, 1H, ArH), 6.68 (br s, 1H, ArH),
3H, CH3); 13C NMR (150 MHz, CDCl3)
d
: 179.3, 161.7, 159.7, 158.1,
139.3, 137.6, 131.2, 130.4, 129.3, 128.8, 128.6, 126.6, 126.2, 125.5,
114.1, 113.9, 110.0, 109.9, 52.1, 51.4, 47.8, 44.9, 37.7, 21.3; IR (KBr)
4.28 (br s, 1H, CH), 3.56 (s, 3H, OCH3), 3.33 (s, 3H, OCH3), 2.20 (s, 3H,
CH3), 1.29 (s, 9H, CH3); 13C NMR (150 MHz, DMSO-d6)
d: 160.9, 151.1,
n
:
140.3, 135.2, 134.2, 133.4, 132.6, 132.1, 129.9, 129.7, 129.5, 128.2,
128.1, 127.8, 127.5, 126.8, 125.4, 124.1, 116.8, 108.7, 52.3, 52.2, 44.0,
34.4, 30.9, 20.6; IR (KBr) n: 3166, 3034, 2966, 2948, 1708,1627, 1565,
1514,1484,1447,1403,1356,1322,1295,1246,1205,1177,1139,1087,
1039, 1017, 983, 954, 884, 833, 805 cmꢁ1; MS (m/z): HRMS (ESI)
calcd for C33H30N2O5 ([MꢁH]ꢁ): 569.1849. Found: 569.184.
3331, 2949, 2837, 1736, 1691, 1613, 1562, 1496, 1449, 1389, 1356,
1290, 1249, 1219, 1174, 1133, 1111, 1088, 1026, 962, 919, 885, 841,
786 cmꢁ1; MS (m/z): HRMS (ESI) calcd for C31H26FN2O5 ([MꢁH]ꢁ):
525.1831. Found: 525.1825.
3.2.15. Compound 4o. White solid, 89%, mp 177e179 ꢀC; 1H NMR
3.2.10. Compound 4j. White solid, 75%, mp 236e238 ꢀC; 1H NMR
(600 MHz, DMSO-d6) d: 10.63 (s, 1H, NH), 7.33e7.18 (m, 8H, ArH),
(600 MHz, DMSO-d6) d: 7.40 (s, 2H, ArH), 7.32e7.22 (m, 6H, ArH),
7.15 (br s, 7H, ArH), 6.85 (br s, 1H, ArH), 5.00e4.61 (m, 3H, CH2, CH),
3.58 (s, 3H, OCH3), 3.20 (s, 3H, OCH3), 2.27 (s, 3H, CH3), 2.22 (s, 3H,
7.06 (s, 1H, ArH), 6.82 (br s, 3H, ArH), 4.40 (br s, 1H, CH), 3.67 (s, 3H,
CH3); 13C NMR (150 MHz, DMSO-d6)
d
: 176.6, 164.8, 162.5, 143.6,
139.4,137.6,135.8,132.7,132.2,130.5,130.1,129.8,129.1,128.8,128.7,
127.5, 124.7, 116.7, 111.1, 53.6, 52.4, 45.0, 44.7, 22.1, 21.9; IR (KBr)
OCH3), 3.56 (s, 3H, OCH3), 3.35 (s, 3H, OCH3); 13C NMR (150 MHz,
DMSO-d6)
128.6, 128.5, 128.0, 127.4, 125.1, 123.3, 120.9, 115.6, 113.6, 110.3, 55.0,
52.0, 50.9; IR (KBr) : 2949, 2837, 1736, 1691, 1613, 1563, 1525, 1496,
1450, 1390, 1356, 1290, 1249, 1219, 1174, 1133, 1111, 1088, 1027, 963,
d: 161.0, 159.2, 141.8, 137.1, 133.4,,132.3, 132.2, 132.1,
n
:
3027, 2947, 2918, 2888,1711, 1608, 1563, 1515,1492, 456, 1430, 1356,
1302, 1251, 1218, 1189, 1166, 1129, 1089, 1020, 969, 927, 895, 847,
n

8260
Y. Han et al. / Tetrahedron 68 (2012) 8256e8260
816, 775 cmꢁ1; MS (m/z): HRMS (ESI) calcd for C37H30ClN2O5
([MꢁH]ꢁ): 617.1849. Found: 617.1833.
References and notes
1. Trofimov, B. A.; Sobenina, L. N.; Demenev, A. P.; Mikhaleva, A. I. Chem. Rev. 2004,
104, 2481e2506.
2. Gale, P. A. Acc. Chem. Res. 2006, 39, 465e475.
3.2.16. Compound 4p. White solid, 77%, mp 246e248 ꢀC; 1H NMR
(600 MHz, DMSO-d6)
d
: 10.54 (s, 1H, NH), 7.26e7.07 (m, 6H, ArH),
3. Boger, D. L.; Boyce, C. W.; Labroli, M. A.; Sehon, C. A.; Jin, Q. J. Am. Chem. Soc.
1999, 121, 54e62.
4. Nadeau, J. M.; Swager, T. M. Tetrahedron 2004, 60, 7141e7146.
5. (a) Yan, R. L.; Luo, J.; Wang, C. X.; Ma, C. W.; Huang, G. S.; Liang, Y. M. J. Org.
Chem. 2010, 75, 5395e5397; (b) Guan, Z. H.; Yan, Z. Y.; Ren, Z. H.; Liu, X. Y.;
Liang, Y. M. Chem. Commun. 2010, 2823e2825.
6.88e6.79 (m, 5H, ArH), 4.33 (br s, 1H, CH), 4.03e4.00 (m, 2H, CH2),
3.78 (br s, 2H, CH2), 3.73 (s, 3H, OCH3), 3.69(s,3H, OCH3),1.03e0.97(m,
6H, CH3); 13C NMR (150 MHz, DMSO-d6)
d
: 160.5, 159.2, 158.8, 141.8,
141.7, 132.3, 132.1, 129.8, 129.4, 127.6, 127.3, 125.1, 123.4, 121.2, 113.6,
110.2, 60.8, 59.7, 55.2, 55.0, 13.6, 13.5; IR (KBr) : 3166, 2968, 2936,
6. Wrtz, S.; Rakshit; Neumann, S. J. J.; Droge, T.; Glorius, F. Angew. Chem., Int. Ed.
2008, 47, 7230e7233.
n
2838, 1709, 1615, 1569, 1513, 1474, 1449, 1410, 1377, 1297, 1247, 1201,
1173, 1129, 1084, 1032, 941, 909, 886, 835, 810, 790 cmꢁ1; MS (m/z):
HRMS (ESI) calcd for C32H28ClN2O7 ([MꢁH]ꢁ): 587.1591. Found:
587.158.
7. (a) Bernini, R.; Fabrizi, G.; Sferrazza, A.; Cacchi, S. Angew. Chem., Int. Ed. 2009, 48,
8078e8081; (b) Neumann, J. J.; Suri, M.; Glorius, F. Angew. Chem., Int. Ed. 2010,
49, 7790e7794.
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Y.; Zhao, K. Org. Lett. 2009, 11, 2417e2420; (c) Liu, W. B.; Jiang, H. F.; Huang, L. B.
Org. Lett. 2010, 12, 312e315.
3.2.17. Compound 4q. White solid, 79%, mp 258e260 ꢀC; 1H NMR
(600 MHz, DMSO-d6) d: 10.54 (s, 1H, NH), 7.20e7.18 (m, 2H, ArH),
9. Shaabani, A.; Teimouri, M. B.; Arab-Ameri, S. Tetrahedron Lett. 2004, 45,
8409e8413.
10. Nair, V.; Menon, R. S.; Deepthi, A.; Devi, B. R.; Biju, A. T. Tetrahedron Lett. 2005,
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11. Yavari, I.; Mokhtarporyani-Sanandaj, A.; Moradi, L.; Mirzaei, A. Tetrahedron
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2563e2566.
7.14e7.06 (m, 8H, ArH), 6.79 (br s, 1H, ArH), 4.35 (br s, 1H, CH),
4.05e4.00 (m, 2H, CH2), 3.79 (br s, 2H, CH2), 2.26 (s, 3H, CH3), 2.22 (s,
3H, CH3), 1.02e0.98 (m, 6H, CH3); 13C NMR (150 MHz, DMSO-d6)
d:
177.6, 163.6, 161.0, 142.3, 138.4, 135.1, 132.5, 131.3, 131.0, 129.5, 129.3,
129.1,128.3,127.8,126.7,125.5,123.9,116.6,115.7,110.7, 61.4, 60.2, 44.7,
44.6, 21.2, 21.0,14.1,13.9; IR (KBr) n: 3166, 3047, 2977, 2859,1708,1616,
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1824e1827.
1573, 1517, 1499, 1471, 1448, 1411, 1294, 1247, 1200, 1168, 1123, 1081,
1038, 1018, 994, 937, 908, 883, 859, 814, 786 cmꢁ1; MS (m/z): HRMS
(ESI) calcd for C32H28ClN2O5 ([MꢁH]ꢁ): 555.1665. Found: 555.1683.
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Acknowledgements
19. Das, B.; Chinna Reddy, G.; Balasubramanyam, P.; Aneyulu, V. Synthesis 2010,
1625e1628.
This work was financially supported by the National Natural
Science Foundation of China (Grant No. 21172189) and the Priority
Academic Program Development of Jiangsu Higher Education
Institutions.
20. Ghabraie, E.; Balalaie, S.; Bararjanian, M.; Bijanzadeh, H.R.; Rominger, F. Tetrahedron
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Supplementary data
Crystallographic data of 4e (CCDC 869520) have been deposited
at the Cambridge Crystallographic Database Centre. These data can
be obtained free of charge via www.ccdc.ac.ck./data_request/cif.
Supplementary data associated with this article can be found in the
online version, at http://dx.doi.org/10.1016/j.tet.2012.07.056.
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