Synthesis of the functionalized spiro[indoline-3,5′-pyrroline]-2, 2′-diones via three-component reactions of arylamines, acetylenedicarboxylates, and isatins

Article abstract of DOI:10.1016/j.tet.2012.08.030

In the presence of p-toluenesulfonic acid as the catalyst the three-component reactions of arylamines, acetylenedicarboxylates, and isatins showed very interesting molecular diversity. When equal amount of arylamine was used, the three-component reaction

Full text of DOI:10.1016/j.tet.2012.08.030

Tetrahedron 68 (2012) 8539e8544
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Synthesis of the functionalized spiro[indoline-3,50-pyrroline]-2,20-diones via
three-component reactions of arylamines, acetylenedicarboxylates, and isatins
*
Ying Han, Qun Wu, 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 5 May 2012
Received in revised form 14 July 2012
Accepted 10 August 2012
Available online 16 August 2012
In the presence of p-toluenesulfonic acid as the catalyst the three-component reactions of arylamines,
acetylenedicarboxylates, and isatins showed very interesting molecular diversity. When equal amount of
arylamine was used, the three-component reaction resulted in the high yields of functionalized 30-hy-
droxyspiro[indoline-3,50-pyrroline]-2,20-dione derivatives. On the other hand the functionalized 30-N-
arylaminospiro[indoline-3,50-pyrroline]-2,20-diones were also successfully prepared in satisfactory yields
by using 2 M arylamine in the reaction.
Keywords:
Ó 2012 Elsevier Ltd. All rights reserved.
Multicomponent reaction
Domino reaction
Electron-deficient alkyne
Isatin
Spiro compound
1. Introduction
methods resulted in a different class of spirocycles that may show
promise as biologically active compounds. As part of our program
Spiro compounds represent an important class of naturally oc-
curring substances characterized by highly pronounced biological
properties. Spirocyclic oxindole systems are found in a number of
alkaloids.1,2 As a consequence, versatile efficient methods have
been reported for the preparation of spirooxindole-fused hetero-
cycles.3,4 Recent synthetic methods to access spirocyclic oxindoles
include formal cycloaddition,5e7 MoritaeBayliseHillman reac-
tion,7a,8,9 and other cyclization reactions.10 Isatin derivatives are
useful precursors in the synthesis of wide number of spirocyclic
oxindoles.11,12 In the past few years the multicomponent reactions
or domino reactions based on the versatile reactivity of isatin de-
rivatives have become the most widely efficient synthetic methods
for various spirooxindoles.13e16 It has been known that the domino
reactions of isatins with Huisgen’s zwitterions formed in situ from
the reaction of pyridine, quinoline or isoquinoline with electron-
deficient alkynes have become the efficient synthetic procedures
for constructing versatile spirooxindole systems.17,18 Perumal and
co-workers successfully reported the synthesis of spiro[indole-3,40-
pyridines] by the four-component reaction of arylamine, acetyle-
nedicarboxylate, malononitrile, and isatin.19 We found that the
four-component reactions of arylamines, dimethyl acetylenedi-
carboxylate, isatins, and dimedone in acetic acid gave novel spiro
[indoline-3,20-quinoline] derivatives.20 Each of the aforementioned
on the study of developing new multicomponent reactions for the
synthesis of heterocyclic compounds,21 herein we wish to report
the efficient synthesis of the hydroxyl and arylamino substituted
functionalized spiro[indoline-3,50-pyrroline]-2,20-diones from the
three-component reactions of arylamines, acetylenedicarboxylate,
and isatins.
2. Results and discussions
Very recently we reported that the three-component reaction of
arylamines, aromatic aldehydes, and acetylenedicarboxylates to
give the novel polysubstituted 3-hydroxy-2-pyrrolidinones.21d We
envisioned that a spiro compound would be formed if isatin was
utilized in the reaction to replace aromatic aldehydes. Thus our
investigation began with the reaction of p-methoxyaniline, di-
methyl acetylenedicarboxylate, and isatin in ethanol with a catalytic
amount of p-toluensulfonic acid according to the previously estab-
lished reaction conditions. After workup we are pleased to find that
the reaction resulted in a functionalized 30-hydroxyspiro[indoline-
3,50-pyrroline]-2,20-dione 1a in 83% yield. This result clearly in-
dicated that isatin can be used as the third component to provide
a three-component reaction for the synthesis of spiro compounds.
Then under similar reaction conditions various arylamines and
5-methyl, 5-chloro, 5-fluoroisatins were successfully used in
the three-component reaction to give the corresponding poly-
substituted 30-hydroxyspiro[indoline-3,50-pyrroline]-2,20-diones
* 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.2012.08.030

8540
Y. Han et al. / Tetrahedron 68 (2012) 8539e8544
1be1j in good yields (Table 1). The structures of the prepared spiro
[indole-3,50-pyrrole] 1ae1j were fully characterized by 1H and 13C
NMR, HRMS, IR spectra and were further confirmed by single-
crystal X-ray diffraction study performed for compound 1g
(Fig. 1). In the 1H NMR spectra of the spiro compounds 1ae1j the
hydroxyl group displays a broad singlet at about 12.40 ppm and the
cyclic NH unit showed a singlet at about 10.60 ppm.
Analyzing the molecular structures of spiro compounds 1ae1j,
it is very clearly seen that the amino group of arylamine unit was
bridged between the molecules of isatin and carbonyl group of
acetylenedicaroboxylate, which indicates arylamine did not react
with acetylenedicarboxylate to give the expected active in-
termediate b-enamino ester in the reaction. Thus further reaction
of dimethyl acetylenedicarboxylate, isatin, and 2 M equiv of p-to-
Table 1
Synthesis of 30-hydroxyspiro[indoline-3,50-pyrroline]-2,20-diones 1ae1j
R
O
CO2CH3
R
CO2CH3
p-TsOH
EtOH
ArNH2
+
+
O
HN
OH
N
CO2CH3
H
N
O
O
Ar
Entry
Compd
Ar0
R
Yield (%)
1
2
3
4
5
6
7
8
9
1a
1b
1c
1d
1e
1f
1g
1h
1i
p-CH3OC6H4
p-CH3C6H4
p-CH3OC6H4
p-C2H5OC6H4
p-ClC6H4
p-CH3C6H4
p-CH3OC6H4
p-ClC6H4
H
83
79
86
84
74
81
84
71
73
70
Me
Me
Me
Me
F
F
F
F
Cl
p-BrC6H4
p-ClC6H4
10
1j
luidine in ethanol with p-toluensulfonic acid as acid catalyst was
carried out. After workup, we found that instead of isolating the
hydroxyl substituted spiro compound,
a
30-N-arylaminospiro
[indoline-3,50-pyrroline]-2,20-dione was successfully obtained as
main product. In order to increase the yields and selectivity the
reaction conditions of this acid-catalyzed three-component re-
action were carefully examined. It is better to let isatin react with
2 M p-toluidine in ethanol at room temperature with 20% molar
ratio of p-toluensulfonic acid as acid catalyst for about 1 h. Then
dimethyl acetylenedicarboxylate was introduced and the reaction
was furnished on reflux in 6 h to give the expected 30-N-p-meth-
ylphenylaminospiro[indoline-3,50-pyrroline]-2,20-dione 2a in 86%
yield (Table 2). Afterward, with the optimized conditions in hand,
we turned our attention to examine the scope of the reaction.
Under this optimized reaction conditions, other arylamines and 5-
methyl, 5-chloro, 5-fluoroisatins reacted smoothly with dimethyl
or diethyl acetylenedicarboxylate to give the corresponding 30-N-p-
Fig. 1. Molecular structure of spiro[indoline-3,50-pyrroline]-2,20-dione 1g.
Table 2
Synthesis of 30-N-arylaminospiro[indoline-3,50-pyrroline]-2,20-diones 2ae2j
R'
CO R
O
2
'
CO R
R
2
p-TsOH
+
+
2 ArNH
HN
2
O
NHAr
EtOH
N
CO R
N
2
H
O
O
Ar
Entry
Compd
Ar0
R
R0
Yield (%)
1
2
3
4
5
6
7
8
9
10
2a
2b
2c
2d
2e
2f
2g
2h
2i
p-CH3C6H4
m-NO2C6H4
Me
H
H
H
Me
Me
F
Cl
Cl
Me
Cl
86
89
72
85
87
84
81
82
69
64
Me
Me
Me
Me
Me
Me
Me
Et
a
-Naph
p-CH3C6H4
m-NO2C6H4
p-CH3C6H4
p-CH3C6H4
p-CH3OC6H4
p-CH3C6H4
p-CH3C6H4
2j
Et

Y. Han et al. / Tetrahedron 68 (2012) 8539e8544
8541
methylphenylaminospiro[indoline-3,50-pyrroline]-2,20-diones
2be2j in good yields (Table 2, entries 2e10). The structures of the
prepared 30-N-arylaminospiro[indoline-3,50-pyrroline]-2,20-diones
2ae2j were established by 1H and 13C NMR, HRMS, IR spectra. The
molecular structure of spiro compound 2f was successfully de-
termined by X-ray single-crystal diffraction method (Fig. 2). In 1H
NMR spectra of 30-N-arylaminospiro[indoline-3,50-pyrroline]-2,20-
diones 2ae2j the amino group usually show a singlet at about
9.20 ppm and the cyclic NH unit displays a singlet at about
10.60 ppm.
in the system as the nucleophile adds to acetylenedicarboxylate to
give a 1,3-dipolar intermediate (C).21d Then the 1,3-dipolar in-
termediate (C) reacts with 3-N-aryliminoisatin (A) to give an ad-
dition intermediate (D). The intramolecular ammonolysis of one
esteric carbonyl group forms the final 30-hydroxyspiro[indoline-
3,50-pyrroline]-2,20-dione 1. In this reaction process the key step is
the formation of active b-enamino ester (B) and its hydroxyl analog
(C), which controls the selective formation of the arylamino and
hydroxyl substituted spiro[indoline-3,50-pyrroline] derivatives. It
should be pointed out that the in situ formation of b-enamino ester
(B) is supported by many reactions containing arylamine and
acetylenedicarboxylate,17e20 while at present the generation of its
hydroxyl analog (C) from the addition of water to acetylenedi-
carboxylate was only our tentative proposal based on the previous
similar reaction21d and more stronger experimental supports are
needed.
In summary we have developed the efficient procedures for
the selective synthesis of two kinds of the functionalized [indo-
line-3,50-pyrroline]-2,20-diones
via
acid-catalyzed
three-
component reactions of arylamine, acetylenedicarboxylate, and
isatin under different conditions. The advantages of the reactions
are using common starting material, mild reaction conditions,
operational simplicity, and wide variety of substrates. The po-
tential uses of the reaction in synthetic and medicinal chemistry
might be quite significant. Further expansion of the reaction scope
and synthetic applications of this methodology are in progress in
our laboratory.
Fig. 2. Molecular structure of spiro[indoline-3,50-pyrroline]-2,20-dione 2f.
On the basis of the above experimental results together with the
related reactions,20e22 a plausible reaction mechanism for this
three-component reaction to give the two kinds of spiro[indoline-
3,50-pyrroline]-2,20-diones is outlined in Scheme 1. The first step in
the reaction is the formation of 3-N-aryliminoisatin (A) from the
condensation of arylamine and isatin with the catalysis of p-tol-
uenesulfonic acid. When 2 M arylamine was used, the second step
is the reaction of remaining arylamine with acetylenedicarboxylate
3. Experimental section
3.1. Reagents and apparatus
Reagents and solvents were commercial available with ana-
lytical grade. Melting points were determined on a hot-plate
microscope apparatus and were uncorrected. Analytical thin-
layer chromatography (TLC) was performed on silica gel plates
with GF-254 indicator, visualized by irradiation with UV light. IR
spectra were obtained on a Bruker Tensor27 spectrometer (KBr
disc). 1H NMR and 13C NMR spectra were measured with a Bruker
to form the active intermediate
b-enamino ester (B). Then the ad-
dition of -enamino ester (B) to 3-N-aryliminoisatin (A) resulted in
b
an adduct (E). The intramolecular reaction of arylamino group with
the ester group with the elimination of methanol gave the final 30-
N-arylaminospiro[indoline-3,50-pyrroline]-2,20-dione 2. On the
other hand if only 1 M arylamine was used, it is believed that water
CO2R
CO2R
OH
CO2R
RO2C
ArHN
+
H2O
+
+
ArNH2
RO2C
(C)
CO2R
(B)
CO2R
CO2R
O
b
HO
RO2C
a
Ar
N
O
OR
Ar
O
H
N
b
O
O
ArNH2
ArHN
N
N
N
H
_
H
H
(A)
(D)
ROH
a
O
ArHN
RO2C
HO
RO2C
O
O
N
OR
Ar
O
RO2C
H
N
_
N
Ar
O
ROH
Ar
O
N
H
N
H
N
H
2
(E)
1
Scheme 1. Proposed formation mechanism of spiro[indoline-3,50-pyrroline]-2,20-dione.

8542
Y. Han et al. / Tetrahedron 68 (2012) 8539e8544
AV-600 spectrometer. High-resolution mass (ESI) spectra were
obtained with a Bruker MicroTOF spectrometer. X-ray data were
collected on a Bruker Smart APEX-2 CCD diffractometer.
799, 781, 767 cmꢁ1; HRMS (ESI) calcd for C22H19N2O6 ([MꢁH]ꢁ):
407.1249. Found: 407.1248.
3.2.5. 10-p-Chlororphenyl-30-hydroxy-40-methoxycarbonyl-5-
3.2. General procedure for the synthesis of the functionalized
methylspiro[indoline-3,50-pyrroline]-2,20-dione (1e). White solid,
spiro[indoline-3,50-pyrroline]-2,20-diones 1ae1j
74%, mp 242e244 ꢀC; 1H NMR (600 MHz, DMSO-d6)
d: 12.48 (br s,
1H, OH), 10.77 (s, 1H, NH), 7.38 (d, J¼8.4 Hz, 2H, ArH), 7.14 (s, 1H,
A solution of arylamine (2.0 mmol) and acetylenedicarboxylate
(2.0 mmol, 0.284 g) in 10 mL ethanol was stirred at room tem-
perature for 10 min. Then isatin (2.0 mmol) and p-toluenesulfonic
acid (2.0 mmol) were added to it and the mixture was stirred at
about 40e50 ꢀC for about 24 h. The solution was then concen-
trated to half the volume. The resulting precipitates were col-
lected and washed with ethanol to give the pure product for
analysis.
ArH), 7.02e7.00 (m, 3H, ArH), 6.68 (d, J¼7.8 Hz, 1H, ArH), 3.56 (s,
3H, OCH3), 2.18 (s, 3H, CH3); 13C NMR (150 MHz, DMSO-d6)
d:
173.2, 165.3, 161.6, 154.5, 140.7, 133.8, 132.4, 131.3, 130.6, 129.2,
128.2, 124.8, 124.6, 110.1, 109.8, 69.7, 51.3, 20.5; IR(KBr) : 3276,
2992, 2948, 1725, 1625, 1496, 1463, 1419, 1355, 1322, 1238, 1197,
n
1149, 1089, 1019, 966, 951, 891, 848, 817, 797, 767, 752 cmꢁ1
;
HRMS (ESI) calcd for C20H14ClN2O5 ([MꢁH]ꢁ): 397.0597. Found:
397.0593.
3.2.1. 30-Hydroxy-40-methoxycarbonyl-10-p-methoxyphenylspiro[in-
3.2.6. 5-Fluoro-30-hydroxy-40-methoxycarbonyl-10-p-methyl-
doline-3,50-pyrroline]-2,20-dione (1a). Yellow solid, 83%, mp
phenylspiro[indoline-3,50-pyrroline]-2,20-dione (1f). White solid,
222e224 ꢀC; 1H NMR (600 MHz, DMSO-d6)
d: 12.40 (br s, 1H, OH),
81%, mp 246e248 ꢀC; 1H NMR (600 MHz, DMSO-d6)
d: 12.46 (br s,
10.77 (s, 1H, NH), 7.30 (d, J¼7.8 Hz, 1H, ArH), 7.18 (t, J¼7.8 Hz, 1H,
ArH), 6.93 (t, J¼7.2 Hz, 1H, ArH), 6.88 (d, J¼9.0 Hz, 2H, ArH), 6.82 (d,
J¼9.0 Hz, 2H, ArH), 6.75 (d, J¼7.2 Hz, 1H, ArH), 3.66 (s, 3H, OCH3),
1H, OH), 10.80 (s, 1H, NH), 7.37 (d, J¼6.0 Hz, 1H, ArH), 7.10 (d,
J¼7.8 Hz, 2H, ArH), 7.00 (t, J¼7.8 Hz, 1H, ArH), 6.90 (d, J¼7.8 Hz, 2H,
ArH), 6.74e6.72 (m, 1H, ArH), 3.57 (s, 3H, OCH3), 2.21 (s, 3H, CH3);
3.55 (s, 3H, OCH3); 13C NMR (150 MHz, DMSO-d6)
d
: 173.5, 165.4,
13C NMR (150 MHz, DMSO-d6)
d
: 173.6, 165.2, 161.8, 158.9, 157.3,
155.2, 139.4, 137.8, 132.0, 129.6, 126.9, 126.8, 126.7, 116.5, 116.4,
112.6, 112.5, 111.0, 110.9, 109.0, 69.9, 51.3, 20.5; IR (KBr) : 3259,
161.8, 158.7, 154.9, 143.3, 130.1, 128.6, 127.0, 124.9, 124.4, 122.1, 114.2,
110.2, 109.4, 70.0, 55.1, 51.2; IR (KBr) : 3290, 2956, 2844, 1721, 1619,
1585, 1516, 1459, 1419, 1360, 1331, 1302, 1280, 1256, 1205, 1179,
n
n
3045, 2962, 1722, 1629, 1515, 1490, 1463, 1421, 1351, 1319, 1266,
1244, 1210, 1172, 1130, 1083, 1025, 1015, 979, 948, 937, 882, 858,
844, 825, 805, 765 cmꢁ1; HRMS (ESI) calcd for C20H14FN2O5
([MꢁH]ꢁ): 381.0892. Found: 381.0891.
1160, 1132, 1112, 1089, 1027, 943, 924, 881, 790, 765, 755 cmꢁ1
;
HRMS (ESI) calcd for C20H15N2O6 ([MꢁH]ꢁ): 379.0936. Found:
379.0936.
3.2.2. 30-hydroxy-40-methoxycarbonyl-5-methyl-10-p-methyl-
3.2.7. 5-Fluoro-30-hydroxy-40-methoxycarbonyl-10-p-methox-
phenylspiro[indoline-3,50-pyrroline]-2,20-dione (1b). white solid,
yphenylspiro[indoline-3,50-pyrroline]-2,20-dione (1g). Yellow solid,
79%, mp 239e241 ꢀC; 1H NMR (600 MHz, DMSO-d6)
d
: 12.39 (br s,
84%, mp 250e252 ꢀC; 1H NMR (600 MHz, DMSO-d6)
d: 12.47 (br s,
1H, OH), 10.68 (s, 1H, NH), 7.10e6.98 (m, 4H, ArH), 6.87 (s, 2H, ArH),
1H, OH), 10.79 (s, 1H, NH), 7.39 (d, J¼7.8 Hz, 1H, ArH), 7.03e6.99 (m,
1H, ArH), 6.93 (d, J¼8.4 Hz, 2H, ArH), 6.86 (d, J¼8.4 Hz, 2H, ArH),
6.74e6.72 (m, 1H, ArH), 3.68 (s, 3H, OCH3), 3.57 (s, 3H, OCH3); 13C
6.65 (s, 1H, ArH), 3.55 (s, 3H, OCH3), 2.19 (s, 6H, CH3); 13C NMR
(150 MHz, DMSO-d6)
131.1, 130.4, 129.5, 126.6, 124.9, 124.7, 109.9, 109.5, 69.8, 51.2, 20.5;
IR(KBr) : 3281, 2957, 2923, 1735, 1653, 1625, 1515, 1495, 1458, 1417,
d: 173.4, 165.2, 161.7, 154.8, 140.8, 137.5, 132.2,
NMR (150 MHz, DMSO-d6)
155.2, 139.4, 128.7, 126.9, 126.8, 116.5, 116.4, 114.3, 112.7, 112.5, 110.9,
110.8,108.9, 70.1, 55.1, 51.3; IR (KBr) : 3273, 3046, 2962, 2842,1720,
d: 173.6, 165.3, 161.8, 158.9, 158.8, 157.3,
n
1353, 1267, 1239, 1201, 1151, 1093, 1025, 1014, 967, 946, 936, 924,
886, 846, 826, 811, 764 cmꢁ1; HRMS (ESI) calcd for C21H17N2O5
([MꢁH]ꢁ): 377.1143. Found: 377.1141.
n
1628,1612,1584,1515,1490,1461,1446,1421,1360,1325,1303,1281,
1257, 1208, 1172, 1128, 1084, 1028, 982, 952, 933, 890, 881, 846, 822,
804, 765 cmꢁ1
397.0841. Found: 397.0840.
;
HRMS (ESI) calcd for C20H14FN2O6([MꢁH]ꢁ):
3.2.3. 30-Hydroxy-40-methoxycarbonyl-10-p-methoxyphenyl-5-
methylspiro[indoline-3,50-pyrroline]-2,20-dione (1c). White solid,
86%, mp 241e242 ꢀC; 1H NMR (600 MHz, DMSO-d6)
d: 12.34 (br s,
3.2.8. 10-p-Chlorophenyl-5-fluoro-30-hydroxy-40-methox-
ycarbonylspiro[indoline-3,50-pyrroline]-2,20-dione (1h). White solid,
1H, OH), 10.63 (s, 1H, NH), 7.12 (s, 1H, ArH), 6.99 (d, J¼7.8 Hz, 1H,
ArH), 6.87e6.82 (m, 4H, ArH), 6.63 (d, J¼7.8 Hz, 1H, ArH), 3.68 (s,
3H, OCH3), 3.56 (s, 3H, OCH3), 2.21 (s, 3H, CH3); 13C NMR (150 MHz,
71%, mp 216e218 ꢀC; 1H NMR (600 MHz, DMSO-d6)
d: 12.59 (br s,
1H, OH), 10.90 (s, 1H, NH), 7.41 (d, J¼9.0 Hz, 3H, ArH), 7.06e7.01 (m,
DMSO-d6)
128.5, 127.1, 124.9, 124.8, 114.2, 109.9, 109.4, 70.0, 55.2, 51.2, 20.5; IR
(KBr) : 3296, 2960, 2842, 1720, 1651, 1625, 1611, 1584, 1514, 1495,
d: 173.4, 165.3, 161.7, 158.6, 154.8, 140.8, 131.1, 130.4,
3H, ArH), 6.77e6.75 (m, 1H, ArH), 3.57 (s, 3H, OCH3); 13C NMR
(150 MHz, DMSO-d6)
132.6, 129.3, 128.6, 126.5, 116.8, 116.6, 112.7, 112.6, 111.1, 111.0, 109.2,
69.8, 51.4; IR(KBr) : 3256, 2961, 1731, 1491, 1465, 1423, 1351, 1318,
d: 173.4, 165.2, 161.7, 157.3, 154.9, 139.4, 133.6,
n
1457, 1418, 1361, 1255, 1206, 1173, 1150, 1112, 1095, 1028, 970, 953,
942, 932, 885, 848, 822, 791, 763 cmꢁ1; HRMS (ESI) calcd for
C21H17N2O6 ([MꢁH]ꢁ): 393.1092. Found: 393.1092.
n
1265, 1212, 1171, 1127, 1093, 1048, 1019, 980, 947, 935, 890, 877, 847,
827, 804, 766, 753 cmꢁ1; HRMS (ESI) calcd for C19H11ClFN2O5
([MꢁH]ꢁ): 401.0346. Found: 401.0345.
3.2.4. 10-p-Ethoxyphenyl-30-hydroxy-40-methoxycarbonyl-5-
methylspiro[indoline-3,50-pyrroline]-2,20-dione (1d). Yellow solid,
3.2.9. 10-p-Bromophenyl-5-fluoro-30-hydroxy-40-methox-
ycarbonylspiro[indoline-3,50-pyrroline]-2,30-dione (1i). White solid,
84%, mp 239e240 ꢀC; 1H NMR (600 MHz, DMSO-d6)
d: 12.33 (br s,
1H, OH), 10.63 (s, 1H, NH), 7.11 (s, 1H, ArH), 6.99 (d, J¼6.6 Hz, 1H,
73%, mp 230e232 ꢀC; 1H NMR (600 MHz, DMSO-d6)
d: 12.59 (br s,
ArH), 6.86e6.81 (m, 4H, ArH), 6.64 (d, J¼6.6 Hz, 1H, ArH), 3.93 (br s,
1H, OH), 10.92 (s, 1H, NH), 7.53 (d, J¼8.4 Hz, 2H, ArH), 7.41 (d,
2H, OCH2), 3.55 (s, 3H, OCH3), 2.20 (s, 3H, CH3), 1.26 (s, 3H, CH3); 13
C
J¼8.4 Hz, 1H, ArH), 7.02 (d, J¼8.4 Hz, 3H, ArH), 6.78 (d, J¼8.4 Hz, 1H,
NMR (150 MHz, DMSO-d6)
131.1, 130.4, 128.4, 127.0, 124.9, 124.8, 114.6, 114.5, 109.9, 109.4, 70.0,
63.1, 51.2, 20.5, 14.5; IR (KBr) : 3359, 2988, 2956, 2906, 1724, 1650,
d
: 173.4, 165.3, 161.7, 158.0, 154.9, 140.8,
ArH), 3.57 (s, 3H, OCH3); 13C NMR (150 MHz, DMSO-d6)
d: 173.5,
165.2, 161.7, 158.9, 157.3, 154.9, 139.4, 134.0, 132.2, 128.8, 126.5,
126.4, 121.2, 116.8, 116.6, 112.7, 112.5, 111.1, 111.0, 109.3, 69.7, 51.3; IR
n
1624, 1610, 1586, 1513, 1493, 1457, 1421, 1366, 1310, 1236, 1198, 1175,
1146, 1113, 1095, 1044, 1018, 968, 952, 927, 902, 890, 845, 827, 817,
(KBr)
n: 3256, 3092, 2961, 1722, 1490, 1465, 1423, 1350, 1317, 1266,
1211, 1171, 1127, 1074, 1047, 1017, 980, 947, 934, 890, 877, 846, 826,

Y. Han et al. / Tetrahedron 68 (2012) 8539e8544
8543
814, 804, 766 cmꢁ1; HRMS (ESI) calcd for C19H11BrFN2O5 ([MꢁH]ꢁ):
1375, 1308, 1254, 1194, 1173, 1128, 1096, 1074, 1037, 898, 881, 847,
808, 795 cmꢁ1; HRMS (ESI) calcd for C33H24N3O4 ([MꢁH]ꢁ):
526.1761. Found: 526.1760.
444.9841. Found: 444.9841.
3.2.10. 5-Chloro-10-p-chlorophenyl-30-hydroxy-40-methox-
ycarbonylspiro[indoline-3,50-pyrroline]-2,20-dione (1j). Yellow solid,
3.3.4. 40-methoxycarbonyl-5-methyl-10-p-methylphenyl-30-N-p-
methylphenylaminospiro[indoline-3,50-pyrroline]-2,20-dione
(2d). Yellow solid, 85%, mp 249e250 ꢀC; 1H NMR (600 MHz,
70%, mp 248e250 ꢀC; 1H NMR (600 MHz, DMSO-d6)
d
: 12.60 (br s,
1H, OH), 11.03 (s, 1H, NH), 7.57e6.81 (m, 7H, ArH), 3.57 (br s, 3H,
OCH3); 13C NMR (150 MHz, DMSO-d6)
: 173.3, 165.2, 161.7, 155.0,
142.1, 133.6, 132.6, 130.2, 129.3, 128.3, 126.8, 126.4, 124.9, 111.7,
109.2, 69.5, 51.3; IR(KBr) : 3259, 2972, 1723, 1620, 1496, 1480, 1460,
d
DMSO-d6) d: 10.62 (s, 1H, NH), 9.05 (s, 1H, NH), 7.14 (s, 1H, ArH),
7.11e7.07 (m, 4H, ArH), 7.03 (d, J¼7.8 Hz, 2H, ArH), 6.98 (d, J¼7.8 Hz,
1H, ArH), 6.87 (d, J¼7.8 Hz, 2H, ArH), 6.64 (d, J¼7.8 Hz, 1H, ArH),
3.22 (s, 3H, OCH3), 2.28 (s, 3H, CH3), 2.21 (s, 6H, CH3); 13C NMR
n
1419, 1354, 1316, 1231, 1208, 1159, 1092, 1041, 1017, 964, 949, 919,
883, 835, 818, 767, 752 cmꢁ1; HRMS (ESI) calcd for C19H11Cl2N2O5
([MꢁH]ꢁ): 417.0051. Found: 417.0049.
(150 MHz, DMSO-d6)
132.9, 132.4, 131.1, 130.3, 129.5, 128.5, 126.8, 125.7, 124.7, 122.1,
109.8,105.9, 71.0, 50.7, 20.5, 20.4; IR (KBr) : 3365, 3278, 3028, 2951,
2918, 1671, 1638, 1544, 1514, 1495, 1439, 1395, 1355, 1294, 1253,
d: 174.0, 165.5, 162.3, 141.8, 140.8, 137.4, 137.1,
n
3.3. General procedure for the synthesis of the functionalized
spiro[indoline-3,50-pyrroline]-2,20-dione
1230, 1196, 1101, 1034, 972, 932, 888, 852, 813, 780, 766 cmꢁ1
;
HRMS (ESI) calcd for C28H24N3O4 ([MꢁH]ꢁ): 466.1772. Found:
A solution of arylamine (4.0 mmol) and isatin (2.0 mmol) and p-
toluenesulfonic acid (0.5 mmol) in 10 mL ethanol was stirred at
room temperature for about 2 h. Then acetylenedicarboxylate
(2.0 mmol) was added to it and the whole mixture was refluxed for
about 6 h. After cooling to room temperature, the resulting pre-
cipitates were collected and washed with ethanol to give the pure
product for analysis.
466.1770.
3.3.5. 40-Methoxycarbonyl-5-methyl-10-m-nitrophenyl-30-N-m-ni-
trophenylaminospiro[indoline-3,50-pyrroline]-2,20-dione (2e). Yellow
solid, 87%, mp 221e223 ꢀC; 1H NMR (600 MHz, DMSO-d6)
d: 10.96
(s, 1H, NH), 9.67 (s, 1H, NH), 8.10 (d, J¼7.8 Hz, 1H, ArH), 7.99e7.92
(m, 3H, ArH), 7.66e7.53 (m, 4H, ArH), 7.35 (s, 1H, ArH), 7.04 (d,
J¼7.8 Hz, 1H, ArH), 6.73 (d, J¼7.8 Hz, 1H, ArH), 3.33 (s, 3H, OCH3),
3.3.1. 40-Methoxycarbonyl-10-p-methylphenyl-30-N-p-methyl-
2.21 (s, 3H, CH3); 13C NMR (150 MHz, DMSO-d6)
d: 173.4, 165.4,
phenylaminospiro[indoline-3,50-pyrroline]-2,20-dione (2a). Yellow
161.7, 147.8, 147.6, 140.9, 140.7, 140.4, 136.1, 132.2, 131.6, 130.9, 130.7,
129.2, 127.9, 125.2, 124.5, 122.4, 120.3, 117.9, 115.9, 110.3, 110.0, 70.9,
solid, 86%, mp 229e231 ꢀC; 1H NMR (600 MHz, DMSO-d6)
d: 10.74
(s, 1H, NH), 9.08 (s, 1H, NH), 7.31 (d, J¼7.2 Hz, 1H, ArH), 7.18 (t,
J¼7.8 Hz, 1H, ArH), 7.11e7.07 (m, 4H, ArH), 7.02 (d, J¼8.4 Hz, 2H,
ArH), 6.94 (t, J¼7.8 Hz, 1H, ArH), 6.87 (d, J¼8.4 Hz, 2H, ArH), 6.74 (d,
J¼7.8 Hz, 1H, ArH), 3.19 (s, 3H, OCH3), 2.28 (s, 3H, CH3), 2.21 (s, 3H,
51.2, 20.5; IR (KBr) n: 3360, 3269, 2958, 1727, 1630, 1513, 1489, 1462,
1421, 1359, 1301, 1252, 1212, 1171, 1123, 1085, 1031, 933, 890, 824,
803, 764 cmꢁ1; HRMS (ESI) calcd for C26H18N5O8 ([MꢁH]ꢁ):
528.1161. Found: 528.1156.
CH3); 13C NMR (150 MHz, DMSO-d6)
d: 174.1, 165.6, 162.2, 143.2,
141.7,137.5,137.2,132.9,132.3,129.9,129.5,128.5,127.0,125.7,124.3,
122.1, 122.0, 110.1, 105.7, 71.0, 50.6, 20.5; IR (KBr) : 3298, 3195,
3.3.6. 5-Fluoro-40-methoxycarbonyl-10-p-methylphenyl-30-N-p-
methylphenylaminospiro[indoline-3,50-pyrroline]-2,20-dione
(2f). Yellow solid, 84%, mp 264e266 ꢀC; 1H NMR (600 MHz, DMSO-
n
3092, 2949, 1718, 1676, 1625, 1515, 1472, 1417, 1384, 1357, 1330,
1305, 1247, 1215, 1160, 1128, 1110, 1031, 966, 951, 936, 920, 886, 866,
d6)
d
: 10.76 (s, 1H, NH), 9.11 (s, 1H, NH), 7.41 (d, J¼8.4 Hz, 1H, ArH),
824, 811, 789, 762 cmꢁ1
;
HRMS (ESI) calcd for C27H22N3O4
7.11e6.98 (m, 7H, ArH), 6.91 (d, J¼8.4 Hz, 2H, ArH), 6.72 (d,
J¼8.4 Hz, 1H, ArH), 3.22 (s, 3H, OCH3), 2.28 (s, 3H, CH3), 2.22 (s, 3H,
([MꢁH]ꢁ): 452.1616. Found: 452.1613.
CH3); 13C NMR (150 MHz, DMSO-d6)
d: 174.3, 165.4, 162.2, 158.9,
3.3.2. 40-Methoxycarbonyl-10-m-nitrophenyl-30-N-m-nitro-
157.3, 142.1,139.4, 137.6, 137.0, 133.0, 132.2, 129.6, 129.5, 128.4, 127.7,
127.6, 127.1, 126.9, 122.3, 116.3, 116.2, 112.5, 112.4, 110.8, 110.7, 105.0,
71.1, 50.7, 20.5; IR (KBr) n: 3352, 3267, 3035, 2956, 1743, 1706, 1667,
phenylaminospiro[indoline-3,50-pyrroline]-2,20-dione (2b). Yellow
solid, 89%, mp 238e240 ꢀC; 1H NMR (600 MHz, DMSO-d6)
d: 11.07
(s, 1H, NH), 9.71 (s, 1H, NH), 8.10 (d, J¼8.4 Hz, 1H, ArH), 7.99e7.91
(m, 3H, ArH), 7.65 (t, J¼8.4 Hz, 1H, ArH), 7.59e7.52 (m, 4H, ArH),
7.24 (t, J¼7.8 Hz, 1H, ArH), 6.97 (t, J¼7.8 Hz, 1H, ArH), 6.84 (d,
J¼7.8 Hz, 1H, ArH), 3.31 (s, 3H, OCH3); 13C NMR (150 MHz, DMSO-
1639, 1609, 1546, 1514, 1489, 1443, 1399, 1361, 1296, 1277, 1258,
1234, 1203, 1174, 1121, 1089, 1034, 981, 969, 934, 892, 869, 850, 815,
801, 782, 768 cmꢁ1; HRMS (ESI) calcd for C27H21FN3O4 ([MꢁH]ꢁ):
470.1522. Found: 470.1514.
d6) d: 173.5, 165.5, 161.7, 147.9, 147.6, 143.2, 141.0, 140.5, 136.0, 132.5,
130.7,130.6,129.2,127.8,124.8,124.5,122.5,120.6,117.9,115.8,110.5,
109.8, 70.9, 51.2; IR (KBr) : 3342, 3271, 3110, 2949,1723,1694,1650,
3.3.7. 5-Chloro-40-methoxycarbonyl-10-p-methylphenyl-30-N-p-
methylphenylaminospiro[indoline-3,50-pyrroline]-2,20-dione
(2g). Yellow solid, 81%, mp 258e260 ꢀC; 1H NMR (600 MHz,
n
1619, 1596, 1527, 1484, 1470,1437, 1392, 1347, 1266, 1222, 1197, 1159,
1141,1094,1030, 981, 934, 914, 892, 848, 802, 764 cmꢁ1; HRMS (ESI)
calcd for C25H16N5O8 ([MꢁH]ꢁ): 514.1004. Found: 514.1004.
DMSO-d6) d: 10.87 (s, 1H, NH), 9.11 (s, 1H, NH), 7.58 (br s, 1H, ArH),
7.22 (d, J¼8.4 Hz,1H, ArH), 7.11e7.05 (m, 6H, ArH), 6.90 (d, J¼8.4 Hz,
2H, ArH), 6.75 (d, J¼7.8 Hz, 1H, ArH), 3.24 (s, 3H, OCH3), 2.28 (s, 3H,
3.3.3. 40-Methoxycarbonyl-10-
thylaminospiro[indoline-3,50-pyrroline]-2,30-dione
solid, 72%, mp 258e260 ꢀC; 1H NMR (600 MHz, DMSO-d6)
a
-naphthyl-30-N-
(2c). Yellow
: 11.22
a
-naph-
CH3), 2.22 (s, 3H, CH3); 13C NMR (150 MHz, DMSO-d6)
d: 174.1,
165.3, 162.3, 142.2, 142.1,137.6,137.0,133.1,132.2, 129.8, 129.7,129.6,
128.4, 128.0, 126.9, 126.2, 124.7, 122.4, 111.4, 104.8, 70.8, 50.7, 20.5;
d
(s, 1H, NH), 9.26 (s, 1H, NH), 8.55 (d, J¼8.4 Hz, 1H, ArH), 8.26 (d,
J¼7.8 Hz, 1H, ArH), 7.93 (d, J¼8.4 Hz, 1H, ArH), 7.77 (d, J¼7.8 Hz, 1H,
ArH), 7.63e7.51 (m, 6H, ArH), 7.39 (d, J¼8.4 Hz, 1H, ArH), 7.20e7.14
(m, 4H, ArH), 6.70 (t, J¼7.2 Hz, 1H, ArH), 6.54 (d, J¼8.4 Hz, 1H, ArH),
6.49 (d, J¼7.2 Hz, 1H, ArH), 3.36 (s, 3H, OCH3); 13C NMR (150 MHz,
IR (KBr) n: 3353, 3276, 3033, 2953, 2919, 1705, 1545, 1514, 1478,
1441, 1357, 1291, 1256, 1197, 1158, 1108, 1065, 1034, 971, 956, 931,
876, 851, 815, 771 cmꢁ1; HRMS (ESI) calcd for C27H21ClN3O4
([MꢁH]ꢁ): 486.1226. Found: 486.1223.
DMSO-d6)
d
: 181.7, 138.7, 137.2, 134.2, 133.3, 133.2, 133.1, 128.5,
3.3.8. 5-Chloro-40-methoxycarbonyl-10-p-methoxyphenyl-30-N-p-
methoxyphenylaminospiro[indoline-3,50-pyrroline]-2,20-dione
(2h). Yellow solid, 82%, mp 254e256 ꢀC; 1H NMR (600 MHz,
128.1, 128.0, 127.1, 126.2, 126.0, 125.3, 125.2, 122.6, 122.5, 121.9,
121.6, 120.7, 119.6, 119.3, 119.2, 115.7, 112.7, 56.4; IR (KBr) : 3356,
3192, 3060, 1683, 1639, 1607, 1574, 1526, 1493, 1469, 1449, 1412,
n
DMSO-d6) d: 10.83 (s, 1H, NH), 9.04 (s, 1H, NH), 7.59 (s, 1H, ArH),

8544
Y. Han et al. / Tetrahedron 68 (2012) 8539e8544
7.23 (s,1H, ArH), 7.13 (br s, 2H, ArH), 6.92e6.87 (m, 6H, ArH), 6.75 (s,
with this article can be found in the online version, at http://
dx.doi.org/10.1016/j.tet.2012.08.030.
1H, ArH), 3.74 (s, 3H, OCH3), 3.68 (s, 3H, OCH3), 3.26 (s, 3H, OCH3);
13C NMR (150 MHz, DMSO-d6)
d: 174.2, 165.4, 162.4, 158.7, 156.3,
142.7, 142.1, 132.4, 129.8, 128.7, 128.6, 128.2, 127.2, 126.2, 124.7,
124.4, 114.3, 114.2, 113.2, 111.4, 103.5, 70.8, 55.2, 55.1, 50.8; IR (KBr)
References and notes
n
: 3333, 3251, 2955, 2838, 1731, 1627, 1512, 1477, 1363, 1300, 1248,
1. (a) Sundberg, R. J. The Chemistry of Indoles; Academic: New York, NY, 1996; (b)
Abdel-Rahman, A. H.; Keshk, E. M.; Hanna, M. A.; El-Bady, Sh. M Bioorg. Med.
Chem. 2004, 12, 2483e2488.
2. (a) Marti, C.; Carreia, E. M. Eur. J. Org. Chem. 2003, 2209e2219; (b) Ashimori, A.;
Bachand, B.; Overman, L. E.; Poon, D. J. J. Am. Chem. Soc. 1998, 120, 6477e6487.
3. (a) Zhu, S. L.; Jia, S. J.; Zhang, Y. Tetrahedron 2007, 63, 9365e9372; (b) Kumar, R.
S.; Perumal, S. Tetrahedron Lett. 2007, 48, 7164e7168.
4. (a) Shanthi, G.; Subbulakshmi, G.; Perumal, P. T. Tetrahedron 2007, 63,
2057e2063; (b) Mohammadi, A. A.; Dabiri, M.; Qaraat, H. Tetrahedron 2009, 65,
3804e3808.
5. (a) Basavaiah, D.; Reddy, R. K. Org. Lett. 2007, 9, 57e60; (b) Kumar, R. R.; Pe-
rumal, S.; Senthilkumar, P.; Yogeeswari, P.; Sriram, D. Eur. J. Med. Chem. 2009,
44, 3821e3829.
1107, 1067, 1032, 960, 932, 918, 890, 861, 824, 789, 765 cmꢁ1; HRMS
(ESI) calcd for C27H21ClN3O6 ([MꢁH]ꢁ): 518.1124. Found: 518.1123.
3.3.9. 40-Ethoxycarbonyl-5-methyl-10-p-methylphenyl-30-N-p-meth-
ylphenylaminospiro[indoline-3,50-pyrroline]-2,20-dione (2i). Yellow
solid, 69%, mp 235e237 ꢀC; 1H NMR (600 MHz, DMSO-d6)
d: 10.61
(s, 1H, NH), 9.05 (s, 1H, NH), 7.14 (s, 1H, ArH), 7.09 (d, J¼7.2 Hz, 4H,
ArH), 7.02e6.98 (m, 3H, ArH), 6.88e6.85 (m, 2H, ArH), 6.63 (d,
J¼7.8 Hz, 1H, ArH), 3.72e3.64 (m, 2H, OCH2), 2.27 (s, 3H, CH3), 2.21
(s, 6H, CH3), 0.66 (t, J¼7.2 Hz, 3H, CH3); 13C NMR (150 MHz, DMSO-
6. (a) Liu, H.; Dou, D. L.; Shi, D. Q. J. Comb. Chem. 2010, 12, 633e637; (b) Liu, H.;
Dou, G. L.; Shi, D. Q. J. Comb. Chem. 2010, 12, 292e294.
7. (a) Shanmugam, P.; Viswambharan, B.; Madhavan, S. Org. Lett. 2007, 9,
4095e4098; (b) Badillo, J. J.; Arevalo, G. E.; Fettinger, J. C.; Franz, A. K. Org. Lett.
2011, 13, 418e421.
d6) d: 179.3, 170.9, 167.1, 146.6, 146.1, 142.6, 142.4, 137.8, 137.7, 136.3,
135.4, 134.8, 134.7, 133.7, 132.0, 131.9, 131.1, 130.0, 126.8, 115.0, 111.4,
76.4, 64.7, 61.3, 25.8, 25.7, 23.8, 18.9, 18.2; IR (KBr) : 3349, 3289,
2918, 1736, 1698, 1666, 1640, 1611, 1545, 1515, 1495, 1473, 1449,
1374, 1343, 1293, 1251, 1230, 1186, 1099, 1034, 967, 872, 853, 813,
763 cmꢁ1; HRMS (ESI) calcd for C29H26N3O4 ([MꢁH]ꢁ): 480.1929.
Found: 480.1924.
n
8. Shanmugam, P.; Viswambharan, B.; Selvakumar, K.; Madhavan, S. Tetrahedron
Lett. 2008, 49, 2611e2615.
9. (a) Zhang, X. C.; Cao, S. H.; Wei, Y.; Shi, M. Org. Lett. 2011, 13, 1142e1145; (b)
Deng, H. P.; Wei, Y.; Shi, M. Org. Lett. 2011, 13, 3348e3351.
10. (a) Wang, L.; Zhang, Y.; Hu, H. Y.; Fun, H. K.; Xu, J. H. J. Org. Chem. 2005, 70,
3850e3858; (b) Viswambharan, B.; Selvakumar, K.; Madhavan, S.; Shanmugam,
P. Org. Lett. 2010, 12, 2108e2111.
11. (a) Bazgir, A.; Noroozi Tisseh, Z.; Mirzaei, P. Tetrahedron Lett. 2008, 49,
5165e5168; (b) Jadidi, K.; Ghahremanzadeh, R.; Bazgir, A. Tetrahedron 2009, 65,
2005e2009.
3.3.10. 5-Chloro-40-ethoxycarbonyl-10-p-methylphenyl-30-N-p-meth-
ylphenylaminospiro[indoline-3,50-pyrroline]-2,20-dione (2j). Yellow
solid, 64%, mp 247e249 ꢀC; 1H NMR (600 MHz, DMSO-d6)
d: 10.88
12. (a) Gao, S. J.; Tsai, C. H.; Tseng, C.; Yao, C. F. Tetrahedron 2008, 64, 9143e9149;
(b) Chen, W. B.; Wu, Z. J.; Pei, Q. L.; Cun, N. F.; Zhang, X. M.; Yuan, W. C. Org. Lett.
2010, 12, 3132e3135.
(s, 1H, NH), 9.13 (s, 1H, NH), 7.59 (s, 1H, ArH), 7.23 (d, J¼8.4 Hz, 1H,
ArH), 7.12e7.04 (m, 6H, ArH), 6.92 (d, J¼8.4 Hz, 2H, ArH), 6.75 (d,
J¼8.4 Hz, 1H, ArH), 3.73e3.67 (m, 2H, OCH2), 2.27 (s, 3H, CH3), 2.22
(s, 3H, CH3), 0.67 (t, J¼7.2 Hz, 3H, CH3); 13C NMR (150 MHz, DMSO-
13. (a) Mokhtari, J.; Alizadeh, A. Helv. Chim. Acta 2011, 94, 1315e1319; (b) Quiroga,
ꢀ
ꢀ
J.; Portillo, S.; Perez, A.; Galvez, J.; Abonia, R.; Insuasty, B. Tetrahedron Lett. 2011,
52, 2664e2666.
14. (a) Ghahremanzadeh, R.; Sayyafi, M.; Ahadi, S.; Bazgir, A. J. Comb. Chem. 2009,
11, 393e396; (b) Shakibaei, G. I.; Feiz, A.; Khavasi, H. R.; Soorki, A. A.; Bazgir, A.
ACS Comb. Sci. 2011, 13, 96e99.
15. (a) Nair, V.; Menon, R. S.; Sreekanth, A.; Abhilash, N.; Biju, A. T. Acc. Chem. Res.
2006, 39, 520e530; (b) Shaabani, A.; Maleki, A.; Rezayan, A. H.; Sarvary, A. Mol.
Divers. 2011, 15, 41e68.
16. (a) Yadav, J. S.; Reddy, B. V. S.; Yadav, N. N.; Gupta, M. K.; Sridhar, B. J. Org. Chem.
2008, 73, 6857e6859; (b) Alizadeh, A.; Rostamnia, S.; Zhu, L. G. Tetrahedron Lett.
2010, 51, 4750e4754.
d6) d: 174.1, 165.5, 161.8, 142.2, 142.0, 137.6, 137.0, 132.8, 132.3, 129.8,
129.6, 128.4, 128.1, 126.9, 126.1, 124.7, 121.9, 111.4, 105.1, 70.9, 59.6,
20.5, 20.4, 13.0; IR (KBr) : 3338, 3287, 3035, 2919, 1701, 1545, 1514,
1477, 1441, 1374, 1344, 1291, 1253, 1191, 1106, 1065, 1033, 1006, 962,
885, 868, 853, 813, 773 cmꢁ1; HRMS (ESI) calcd for C28H23ClN3O4
([MꢁH]ꢁ): 500.1383. Found: 500.1381.
n
17. (a) Esmaili, A. A.; Bodaghi, A. Tetrahedron 2003, 59, 1169e1171; (b) Esmaeili, A.
A.; Darbanian, M. Tetrahedron 2003, 59, 5545e5548; (c) Nair, V.; Vinod, A. U.;
Abhilash, N.; Menon, R. S.; Santhi, V.; Varma, R. L.; Viji, S.; Mathewa, S.; Srinivas,
R. Tetrahedron 2003, 59, 10279e10286; (d) Nair, V.; Devipriya, S.; Suresh, E.
Tetrahedron 2008, 64, 3567e3577.
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Acknowledgements
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
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available free of charge. Crystallographic data of 1g (CCDC 879517)
and 2f (CCDC 879518) have been deposited at the Cambridge
Crystallographic Database Centre. Supplementary data associated
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