Selective synthesis of functionalized spiro[indoline-3,2′-pyridines] and spiro[indoline-3,4′-pyridines] by lewis acid catalyzed reactions of acetylenedicarboxylate, arylamines, and isatins

Article abstract of DOI:10.1021/jo500144z

The functionalized spiro[indoline-3,2′-pyridine]-3′,4′, 5′,6′-tetracarboxylates were efficiently synthesized by BF ₃·OEt₂-catalyzed reactions of isatin-3-imines with acetylenedicarboxylates in methylene dichloride. Under similar cond

Full text of DOI:10.1021/jo500144z

Note
pubs.acs.org/joc
Selective Synthesis of Functionalized Spiro[indoline-3,2′-pyridines]
and Spiro[indoline-3,4′-pyridines] by Lewis Acid Catalyzed Reactions
of Acetylenedicarboxylate, Arylamines, and Isatins
Hong Gao, Jing Sun, and Chao-Guo Yan*
College of Chemistry & Chemical Engineering, Yangzhou University, Yangzhou 225002, China
S
* Supporting Information
ABSTRACT: The functionalized spiro[indoline-3,2′-pyri-
dine]-3′,4′,5′,6′-tetracarboxylates were efficiently synthesized
by BF3·OEt2-catalyzed reactions of isatin-3-imines with
acetylenedicarboxylates in methylene dichloride. Under similar
conditions, the BF3·OEt2-catalyzed three-component reactions
of acetylenedicarboxylates, arylamines, and isatins afforded
functionalized spiro[indoline-3,4′-pyridine]-2′,3′,5′,6′-tetracar-
boxylates in moderate yields.
Scheme 1. Synthesis of Various Spirooxindoles via Three-
Component Reaction
n the past decades, multicomponent reactions have attracted
Iparticular attention because of their high efficiency in the
construction of complex molecular framework in a single step
from readily available reagents.1 Compared to traditional
stepwise reactions, multicomponent reactions not only have
the advantages of atom economy, simpler procedures, lower
costs, and high variability but also are often accompanied by
significant increases in molecular diversity and impressive
selectivity.2 Thus, the development of new multicomponent
reactions is one of the hottest research topics in organic
synthetic chemistry.3,4 In recent years, Huisgen 1,4-dipoles,
which can be easily generated from the addition reaction of
nitrogen heterocycles or amines to electron-deficient alkynes,5
has been widely recognized as key component for design
versatile multicomponent reactions for developing efficient
synthetic procedures for many nitrogen-containing heterocyclic
systems.6−12 Practically, the three-component reaction of
arylamine, isatin, and acetylenedicarboxylate showed very
interesting molecular diversity. In the presence of p-
toluenesulfonic acid as the catalyst or in the admicellar catalytic
system, the three-component reaction afforded 3′-hydroxy- or
3′-N-arylaminospiro[indoline-3,5′-pyrrolines].13,14 On the
other hand, the three-component reaction resulted in the
functionalized spirolactones and dispirodihydrofuranyl oxin-
doles when triethylamine was used as base catalyst (Scheme
1).15 Very recently, we reported that the three-component
reaction of acetylenedicarboxylates, arylamines, and aromatic
aldehydes resulted in the polysubstituted 1,4-dihydropyridines
in the acidic system.16 We envisioned that the spiro[indoline-
pyridine] derivatives could also be formed when isatin was used
to replace aromatic aldehyde in above three-component
reactions. In continuation of our efforts to explore the practical
applications of Huisgen 1,4-dipoles in multicomponent
reactions, herein we report the selective synthesis of function-
alized spiro[indoline-3,2′-pyridines] and spiro[indoline-3,4′-
pyridines] by Lewis acid catalyzed reactions of acetylenedi-
carboxylate, arylamines, and isatins.
At first, the reaction of isatin-3-imine with dimethyl
acetylenedicarboxylate was investigated. An equivalomolecular
isatin-3-imine and dimethyl acetylenedicarboxylate in methyl-
ene dichloride in the presence of BF3·OEt2 was stirred at
elevated temperature for 7 h. After workup, the expected
spiro[indoline-3,2′-quinoline] was not obtained, which might
be formed from the imine-Diels−Alder reaction.17 Instead,
spiro[indoline-3,2′-pyridine]-3′,4′,5′,6′-tetracarboxylate 1a was
obtained in 48% yield, in which two moieties of acetylenedi-
carboxylate to take part in to form the skeleton of 1,4-
Received: January 20, 2014
Published: April 2, 2014
© 2014 American Chemical Society
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The Journal of Organic Chemistry
Note
1
dihydropyridine. When 2 equiv of acetylenedicarboxylate was
used, 1a was obtained in 65% yield (Table 1, entry 1). The
pyridine]tetracarboxylates were characterized by H and 13C
NMR, HRMS, and IR spectra. The structures of 1e and 1k
were further confirmed by single-crystal X-ray diffraction
method (Figures s1 and s2, Supporting Information).
Table 1. Synthesis of Spiro[indoline-3,2′-pyridine]-
a
A tentative mechanistic rationale portraying the probable
sequence of events is briefly given in Scheme 2 on the basis of
the previous reported reactions of electron-deficient alkynes
with aldimines.18 The first step is the addition of isatin-3-imine
to the triple bond of acetylenedicarboxylate gives one 1,4-
dipolar intermediate (A) under the catalysis of BF3·OEt2.
Second, the 1,4-dipolar intermediate (A) can react with second
acetylenedicarboxylate to give a double addition intermediate
(B). Third, the intramolecular coupling of the negative charge
with the positive charge affords the spiro[indoline-3,2′-
pyridine] 1 as the final product.
In the light of the operational simplicity and mild conditions
of our spiro[indoline-3,2′-pyridine] synthesis, we intended to
expand the above-described protocol to a three-component
reaction. Thus, a mixture of arylamines, isatins, and two
molecular dimethyl acetylenedicarboxylates in methylene
dichloride in the presence of BF3·OEt2 was refluxed for about
1 day. We were pleased to find that the isomeric spiro[indoline-
3,4′-pyridine]-2′,3′,5′,6′-tetracarboxylates 2a−e were obtained
in moderate yields (Table 2). The structures of the spiro-
3′,4′,5′,6′-tetracarboxylates
b
yield
entry compd
R
R′
R″
Ar
(%)
1
2
1a
1b
CH3
CH3
CH3
H
H
p-CH3CH2OC6H4
65
66
CH3
p-
(CH3)2CHC6H4
3
1c
1d
1e
1f
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
Cl
H
H
H
p-(CH3)3CC6H4
p-(CH3)3CC6H4
p-CH3C6H4
p-(CH3)3CC6H4
p-BrC6H4
62
60
63
66
60
70
63
62
68
58
61
4
5
Bn
Bn
Bn
6
H
7
1g
1h
1i
H
8
CH3 Bn
CH3 Bn
CH3 Bn
CH3 Bn
CH3 Bn
CH3 n-
C6H5
9
p-CH3C6H4
p-CH3OC6H4
p-(CH3)3CC6H4
p-BrC6H4
10
11
12
13
1j
Table 2. Synthesis of Spiro[indoline-3,4′-pyridine]-
1k
1l
a
2′,3′,5′,6′-tetracarboxylates
1m
p-CH3C6H4
C4H9
14
15
16
17
18
1n
1o
1p
1q
1r
CH3
Cl
Cl
Cl
Bn
p-CH3C6H4
p-(CH3)3CC6H4
p-ClC6H4
65
60
50
55
72
CH3
Bn
Bn
CH3
CH2CH3
CH2CH3
CH3 Bn
Cl Bn
C6H5
p-CH3C6H4
a
b
.Reaction conditions: acetylenedicarboxylate (2.0 mmol) and isatin-3-
entry
compd
R
R′
R″
yield (%)
imine (1.0 mmol), BF3·OEt2 (0.5 mmol) in CH2Cl2 (10.0 mL), reflux,
24 h. Isolated yield.
b
1
2
3
4
5
2a
2b
2c
2d
2e
p-CH3C6H4
p-CH3OC6H4
p-CH3CH2OC6H4
C6H5
H
H
45
55
55
48
53
H
H
H
H
CH3
CH3
Bn
Bn
yield of spiro compound 1a could not be increased when excess
dimethyl acetylenedicarboxylate was utilized in the reaction.
Similarly, various isatin-3-imines were used in the reactions
under the same conditions. The results are summarized in
Table 1. Isatin itself and its 5-fluoro, 5-chloro, 5-methyl and 1-
benzyl, 1-butyl derivatives showed similar reactivity and reacted
efficiently to give the spiro products (Table 1, entries 1−16). It
should be pointed out that arylamines with alkyl, alkoxy, and
halo groups proceeded smoothly to afford the corresponding
spiro[indoline-3,2′-pyridine]-3′,4′,5′,6′-tetracarboxylates. Di-
ethyl acetylenedicarboxylate also used in the reactions to give
the corresponding tetraethyl spiro[indoline-3,2′-pyridine]-
3′,4′,5′,6′-tetracarboxylates 1q and 1r in good yields (Table
1, entries 17 and 18). The structures of the spiro[indoline-3,2′-
p-CH3OC6H4
a
.Reaction condition: acetylenedicarboxylate (2.0 mmol), isatin (1.0
mmol), arylamine (1.0 mmol), BF3·OEt2 (0.5 mmol) in CH2Cl2 (10.0
b
mL), reflux, 24 h. Isolated yield.
[indoline-3,4′-pyridine] were established with the spectroscopic
methods and confirmed by X-ray determination of single crystal
2b (Figure s3, Supporting Information). Because there is no
direct connection between the moieties of arylamine and
oxindoles, it can be concluded that the isatin-3-imine did not
form in this reaction and this three-component reaction must
proceed with other reaction mechanisms.
Scheme 2. Formation Mechanism of Spiro[indoline-3,2′-pyridine] 1
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Note
Tetramethyl 1′-(4-ethoxyphenyl)-5-methyl-2-oxo-1′H-spiro-
[indoline-3,2′-pyridine]-3′,4′,5′,6′-tetracarboxylate (1a): yellow
In order to explain the formation mechanism of spiro-
[indoline-3,4′-pyridine] 2, a rational domino reaction mecha-
nism is proposed in Scheme 3 based on the reported similar
1
solid, 0.366 g, 65%; mp 248−250 °C; H NMR (600 MHz, DMSO-
d6) δ 10.27 (s, 1H), 7.32 (s, 1H), 7.12−7.07 (m, 2H), 6.87 (d, J = 7.2
Hz, 1H), 6.60−6.55 (m, 2H), 6.20 (d, J = 7.2 Hz, 1H), 3.93 (d, J = 7.2
Hz, 2H), 3.76 (s, 3H), 3.60 (s, 3H), 3.43 (s, 3H), 3.32 (s, 3H), 2.31 (s,
3H), 1.27 (s, 3H); 13C NMR (150 MHz, DMSO-d6) δ 174.4, 166.4,
162.9(2C), 161.9, 158.9, 152.4, 138.5, 138.4, 131.9, 131.7, 131.6,
131.0, 130.8, 128.8, 124.7, 113.7, 113.5, 111.9, 109.9, 93.8, 70.0, 63.3,
52.6, 52.3, 52.0, 51.8, 20.6, 14.4; IR (KBr) ν 3312, 2954, 1742, 1610,
1500, 1435, 1353, 1307, 1247, 1013, 837, 771 cm−1; HRMS (ESI-
TOF) calcd for C29H28N2NaO10 ([M + Na]+) 587.1636, found
587.1636.
Scheme 3. Formation Mechanism of Spiro[indoline-3,4′-
pyridine] 2
Tetramethyl 1′-(4-isopropylphenyl)-5-methyl-2-oxo-1′H-spiro-
[indoline-3,2′-pyridine]-3′,4′,5′,6′-tetracarboxylate (1b): yellow
1
solid, 0.371 g, 66%, mp 230−232 °C; H NMR (600 MHz, DMSO-
d6) δ 10.30 (s, 1H), 7.32 (s, 1H), 7.24−7.22 (m, 1H), 7.12 (d, J = 7.8
Hz, 1H), 7.09−7.07 (m, 1H), 6.97−6.96 (m, 1H), 6.56 (d, J = 7.8 Hz,
1H), 6.25−6.23 (m, 1H), 3.76 (s, 3H), 3.60 (s, 3H), 3.43 (s, 3H), 3.25
(s, 3H), 2.84−2.79 (m, 1H), 2.31 (s, 3H), 1.12−1.10 (m, 6H); 13C
NMR (150 MHz, DMSO-d6) δ 174.3, 166.4, 162.9(2C), 161.9, 152.2,
150.2, 138.3, 138.2, 134.2, 132.0, 131.8, 130.8, 130.0, 129.5, 126.2,
125.8, 124.6, 112.1, 110.0, 94.2, 69.7, 52.4, 52.3, 52.0, 51.9, 32.9, 23.5,
23.4, 20.6; IR (KBr) ν 3299, 2956, 1746, 1606, 1499, 1438, 1350,
1305, 1234, 1009, 826, 776 cm−1; HRMS (ESI-TOF) calcd for
C30H30N2NaO9 ([M + Na]) 585.1844, found 585.1850.
Tetramethyl 1′-(4-tert-butylphenyl)-5-methyl-2-oxo-1′H-spiro-
[indoline-3,2′-pyridine]-3′,4′,5′,6′-tetracarboxylate (1c): yellow
1
solid, 0.357 g, 62%; mp 248−250 °C; H NMR (600 MHz, DMSO-
reactions of electron-deficient alkynes with arylamines and
aromatic aldehydes.16,19,20 First, the addition of arylamine to
acetylenedicarboxylate gives the expected 1,3-dipolar β-
enamino ester (C). Then the nucleophilic addition of
intermediate (C) to the 3-carbonyl group of isatin affords the
intermediate (D). Third, in the presence of stronger Lewis acid
BF3·OEt2, the intermediate (D) was dehydrated to give a
carbocation intermediate (E), which in turn reacts with second
molecular β-enamino ester (C) to give the intermediate (F).
Finally, the intermediate (F) transforms to spiro[indoline-3,4′-
pyridine] 2 by splitting out of one arylamino group. The last
step has been described in the similar formation of 1,4-
dihydropyridine derivatives by TiCl4-catalyzed trimerization of
β-enamino ester and Sc(OTf)3-catalyzed reaction of methyl
propiolate with aromatic aldimines.19,20
In summary, we have found that the isomeric spiro[indoline-
3,2′-pyridines] and spiro[indoline-3,4′-pyridines] can be
selectively and efficiently prepared by the Lewis acid catalyzed
reactions of acetylenedicarboxylates with isatin-3-imines and
three-component reactions of acetylenedicarboxylates with
isatin and arylamines. The rational formation mechanism for
the two isomeric spirooxindoles was briefly discussed. This
reaction has the advantages of the readily variable substrates,
short reaction time, and easiness of handling. The potential
uses of this reaction in synthetic and medicinal chemistry might
be quite significant.
d6) δ 10.31 (s, 1H), 7.39−7.37 (m, 1H), 7.33 (s, 1H), 7.13−7.08 (m,
3H), 6.58 (d, J = 7.8 Hz, 1H), 6.26−6.24 (m, 1H), 3.76 (s, 3H), 3.60
(s, 3H), 3.44 (s, 3H), 3.23 (s, 3H), 2.31 (s, 3H), 1.19 (s, 9H); 13C
NMR (150 MHz, DMSO-d6) δ 174.3, 166.4, 162.9(2C), 161.9, 152.5,
152.2, 138.3, 138.2, 134.0, 132.0, 131.8, 130.8, 129.8, 129.1, 125.3,
124.7, 124.6, 112.1, 110.0, 94.3, 69.7, 52.4, 52.3, 52.0, 51.9, 34.4, 30.8,
20.6; IR (KBr) ν 3289, 2958, 1745, 1711, 1677, 1604, 1498, 1438,
1352, 1306, 1240, 1160, 1127, 1013, 966, 855, 825, 772 cm−1; HRMS
(ESI-TOF) calcd for C31H32N2NaO9 ([M + Na]+) 599.2000, found
599.2000.
Tetramethyl 1′-(4-tert-butylphenyl)-5-chloro-2-oxo-1′H-spiro-
[indoline-3,2′-pyridine]-3′,4′,5′,6′-tetracarboxylate (1d): yellow
1
solid, 0.358 g, 60%, mp >250 °C; H NMR (600 MHz, DMSO-d6)
δ 10.61 (s, 1H), 7.54 (s, 1H), 7.40−7.38 (m, 2H), 7.17 (d, J = 8.4 Hz,
1H), 7.10 (d, J = 8.4 Hz, 1H), 6.72 (d, J = 7.8 Hz, 1H), 6.36 (d, J = 8.4
Hz, 1H), 3.77(s, 3H), 3.61 (s, 3H), 3.46 (s, 3H), 3.25 (s, 3H), 1.20 (s,
9H); 13C NMR (150 MHz, DMSO-d6) δ 174.0, 166.1, 162.8, 162.7,
161.8, 152.7, 152.0, 139.9, 138.6, 133.9, 132.2, 131.5, 129.7, 129.1,
126.4, 125.5, 124.9, 124.2, 111.8, 111.7, 94.8, 69.5, 52.5, 52.4, 52.2,
51.9, 34.5, 30.8; IR (KBr) ν 3268, 2957, 1749, 1710, 1678, 1606, 1502,
1438, 1354, 1309, 1240, 1146, 1048, 1014, 965, 887, 856, 827, 781
cm−1; HRMS (ESI-TOF) calcd for C30H29ClN2NaO9 ([M + Na]+)
619.1454, found 619.1460.
Tetramethyl 1-benzyl-1′-(4-methylphenyl)-2-oxo-1′H-spiro-
[indoline-3,2′-pyridine]-3′,4′,5′,6′-tetracarboxylate (1e): yellow
1
solid, 0.384 g, 63%; mp 172−174 °C; H NMR (600 MHz, DMSO-
d6) δ 7.63 (s, 1H), 7.32 (s, 1H), 7.21−7.16 (m, 5H), 7.07 (s, 1H), 6.85
(s, 1H), 6.76 (s, 2H), 6.70 (s, 1H), 6.18 (s, 1H), 4.72 (d, J = 15.0 Hz,
1H), 4.45 (d, J = 15.0 Hz, 1H), 3.77(s, 3H), 3.62 (s, 3H), 3.37 (s, 3H),
3.30 (s, 3H), 2.26 (s, 3H); 13C NMR (150 MHz, DMSO-d6) δ 173.1,
166.2, 162.8, 161.7, 152.4, 141.5, 139.8, 138.6, 135.1, 133.7, 131.5,
130.0, 129.8, 129.6, 129.4, 128.7, 128.2, 127.3, 127.1, 124.5, 123.8,
112.0, 109.7, 94.4, 69.4, 52.6, 52.4, 52.1, 51.9, 43.4, 20.8; IR (KBr) ν
3005, 2953, 1743, 1702, 1608, 1501, 1440, 1356, 1311, 1247, 1199,
1139, 1022, 995, 953, 904, 848, 815, 761 cm−1; HRMS (ESI-TOF)
calcd for C34H30N2NaO9 ([M + Na]+) 633.1844, found 633.1859.
Tetramethyl 1-benzyl-1′-(4-tert-butylphenyl)-2-oxo-1′H-spiro-
[indoline-3,2′-pyridine]-3′,4′,5′,6′-tetracarboxylate (1f): yellow
EXPERIMENTAL SECTION
■
1. General Procedure for the Preparation of Spiro[indoline-
3,2′-pyridine]tetracarboxylates 1a−r from Reactions of Di-
methyl Acetylenedicarboxylate with Isatin-3-imines. To a
stirred solution of acetylenedicarboxylate (2.0 mmol) and isatin-3-
imine (1.0 mmol) in methylene dichloride (10.0 mL) was added BF3·
OEt2 (0.5 mmol) at room temperature. Then the mixture was refluxed
for about 1 day. The solvent was removed by evaporation, and the
residue was subjected to preparative thin-layer chromatography (25 ×
15 cm SiO2 plate) with a mixture of light petroleum and ethyl acetate
(V/V = 2:1) as developing reagent to give the pure products 1a−r for
analysis.
1
solid, 0.430 g, 66%; mp 90−92 °C; H NMR (600 MHz, DMSO-
d6) δ 7.63 (d, J = 3.6 Hz, 1H), 7.36 (d, J = 4.8 Hz, 1H), 7.20−7.17 (m,
4H), 7.11 (d, J = 4.8 Hz, 2H), 6.88 (s, 2H), 6.67 (d, J = 4.8 Hz, 1H),
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Note
6.27 (d, J = 4.8 Hz, 1H), 4.67 (d, J = 15.6 Hz, 1H), 4.44 (d, J = 15.6
Hz, 1H), 3.77(s, 3H), 3.61 (s, 3H), 3.36 (s, 3H), 3.24 (s, 3H), 1.20 (s,
9H); 13C NMR (150 MHz, DMSO-d6) δ 173.1, 166.2, 162.8, 161.8,
152.7, 152.4, 141.5, 138.5, 135.2, 133.8, 131.5, 129.8, 129.4, 128.3,
127.3, 127.1, 125.6, 124.8, 124.4, 123.8, 112.1, 109.8, 94.5, 69.2,
52.4(2C), 52.1, 51.9, 43.6, 34.5, 30.8; IR (KBr) ν 2955, 1744, 1609,
1504, 1436, 1348, 1311, 1234, 1138, 1015, 958, 829, 750 cm−1; HRMS
(ESI-TOF) calcd for C37H36N2NaO9 ([M + Na]+) 675.2313, found
675.2296.
DMSO-d6) δ 7.43 (s, 1H), 7.36 (d, J = 4.8 Hz, 1H), 7.18 (s, 3H), 7.12
(s, 3H), 6.85 (s, 2H), 6.53 (d, J = 5.4 Hz, 1H), 6.28 (d, J = 4.8 Hz,
1H), 4.63 (d, J = 15.6 Hz, 1H), 4.38 (d, J = 15.6 Hz, 1H), 3.77(s, 3H),
3.61 (s, 3H), 3.35 (s, 3H), 3.23 (s, 3H), 2.32 (s, 3H), 1.21 (s, 9H); 13C
NMR (150 MHz, DMSO-d6) δ 173.2, 166.4, 162.9, 162.8, 161.8,
152.8, 152.4, 139.2, 138.6, 135.2, 133.7, 133.1, 131.8, 130.0, 129.9,
129.6, 128.3, 127.3, 126.9, 125.6, 124.8, 124.7, 111.9, 109.6, 94.1, 69.4,
52.4(2C), 52.2, 51.9, 43.6, 34.5, 30.8, 20.5; IR (KBr) ν 2956, 1744,
1701, 1602, 1500, 1436, 1344, 1309, 1238, 1201, 1152, 998, 955, 824
cm−1; HRMS (ESI-TOF) calcd for C38H38N2NaO9 ([M + Na]+)
689.2470, found 689.2480.
Tetramethyl 1-benzyl-1′-(4-bromophenyl)-5-methyl-2-oxo-1′H-
spiro[indoline-3,2′-pyridine]-3′,4′,5′,6′-tetracarboxylate (1l): yellow
solid, 0.399 g, 58%; mp 220−222 °C; 1H NMR (600 MHz, CDCl3) δ
7.52 (s, 1H), 7.42−7.41 (m, 1H), 7.29−7.27 (m, 1H), 7.25−7.22 (m,
1H), 7.08−7.03 (m, 2H), 6.96 (d, J = 5.4 Hz, 2H), 6.40−6.39 (m,
1H), 6.20−6.19 (m, 1H), 4.81 (d, J = 15.6 Hz, 1H), 4.24 (d, J = 15.6
Hz, 1H), 3.88 (s, 3H), 3.71 (s, 3H), 3.50 (s, 3H), 3.40 (s, 3H), 2.35 (s,
3H); 13C NMR (150 MHz, CDCl3) δ 173.5, 167.1, 163.6, 163.3,
162.5, 152.1, 139.4, 139.3, 135.9, 134.9, 133.8, 133.0, 132.2, 132.1,
131.8, 131.3, 130.4, 128.6, 127.6, 127.1, 125.7, 124.3, 112.3, 109.2,
95.6, 70.1, 52.6, 52.4, 52.2, 52.0, 44.5, 21.1; IR (KBr) ν 3057, 2990,
2946, 1727, 1609, 1523, 1491, 1438, 1408, 1350, 1243, 1198, 1151,
1074, 1008, 960, 898, 818 cm−1; HRMS (ESI-TOF) calcd for
C34H29BrN2NaO9 ([M + Na]+) 711.0949, found 711.0953.
Tetramethyl 1-n-butyl-1′-(4-methylphenyl)-5-methyl-2-oxo-1′H-
spiro[indoline-3,2′-pyridine]-3′,4′,5′,6′-tetracarboxylate (1m): yel-
low solid, 0.360 g, 61%; mp 156−158 °C; 1H NMR (600 MHz,
CDCl3) δ 7.51 (s, 1H), 7.23 (d, J = 7.2 Hz, 1H), 7.13 (d, J = 7.8 Hz,
1H), 7.07 (d, J = 7.8 Hz, 1H), 6.74 (d, J = 7.8 Hz, 1H), 6.49 (d, J = 7.8
Hz, 1H), 6.15 (d, J = 7.8 Hz, 1H), 3.88 (s, 3H), 3.70 (s, 3H), 3.50 (s,
3H), 3.45−3.40 (m, 1H), 3.37 (s, 3H), 3.08−3.03 (m, 1H), 2.38 (s,
3H), 2.24 (s, 3H), 1.06−0.98 (m, 3H), 0.88−0.85 (m, 1H), 0.77 (t, J =
7.2 Hz, 3H); 13C NMR (150 MHz, CDCl3) δ 173.1, 167.4, 163.8,
163.4, 162.7, 152.9, 139.9, 139.8, 139.5, 134.2, 133.2, 131.6, 131.0,
129.9, 129.1, 128.3, 125.8, 111.4, 108.0, 94.6, 70.0, 52.4, 52.1, 51.9,
39.9, 29.0, 21.1, 20.1, 13.8; IR (KBr) ν 2953, 2872, 1718, 1602, 1501,
1437, 1337, 1209, 1155, 1108, 1010, 878, 823, 763 cm−1; HRMS (ESI-
TOF) calcd for C32H34N2NaO9 ([M + Na]+) 613.2157, found
613.2165.
Tetramethyl 1-benzyl-1′-(4-methylphenyl)-5-chloro-2-oxo-1′H-
spiro[indoline-3,2′-pyridine]-3′,4′,5′,6′-tetracarboxylate (1n): yellow
solid, 0.419 g, 65%; mp 190−192 °C; 1H NMR (600 MHz, CDCl3) δ
7.69 (s, 1H), 7.28 (d, J = 8.4 Hz, 1H), 7.19 (t, J = 7.8 Hz, 2H), 7.14 (t,
J = 7.2 Hz, 2H), 7.10 (d, J = 8.4 Hz, 1H), 6.80 (d, J = 7.8 Hz, 1H),
6.65 (d, J = 7.8 Hz, 2H), 6.36 (d, J = 8.4 Hz, 1H), 6.28 (d, J = 7.8 Hz,
1H), 4.79 (d, J = 15.6 Hz, 1H), 4.26 (d, J = 15.6 Hz, 1H), 3.89 (s, 3H),
3.71 (s, 3H), 3.52 (s, 3H), 3.37 (s, 3H), 2.32 (s, 3H); 13C NMR (150
MHz, CDCl3) δ 173.5, 167.0, 163.6, 163.3, 162.4, 152.9, 140.4, 140.2,
140.1, 134.5, 134.1, 132.0, 131.2, 131.0, 130.1, 129.6, 129.0, 128.8,
128.5, 127.5, 127.1, 125.4, 111.2, 110.5, 94.9, 70.0, 52.5(2C), 52.4,
52.1, 44.5, 21.4; IR (KBr) ν 3070, 3004, 2951, 2850, 1745, 1706, 1608,
1450, 1438, 1349, 1315, 1246, 1201, 1143, 1022, 995, 952, 883, 817,
787 cm−1; HRMS (ESI-TOF) calcd for C34H29ClN2NaO9 ([M +
Na]+) 667.1454, found 667.1453.
Tetramethyl 1-benzyl-1′-(4-bromophenyl)-2-oxo-1′H-spiro-
[indoline-3,2′-pyridine]-3′,4′,5′,6′-tetracarboxylate (1g): yellow
1
solid, 0.403 g, 60%; mp 182−184 °C; H NMR (600 MHz, CDCl3)
δ 7.73 (d, J = 7.8 Hz, 1H), 7.43−7.42 (m, 1H), 7.30−7.28 (m, 1H),
7.25−7.22 (m, 4H), 7.13 (t, J = 7.8 Hz, 1H), 7.07−7.06 (m, 1H), 6.69
(d, J = 7.2 Hz, 2H), 6.51 (d, J = 7.8 Hz, 1H), 6.19−6.17 (m, 1H), 4.86
(d, J = 16.2 Hz, 1H), 4.27 (d, J = 16.2 Hz, 1H), 3.88 (s, 3H), 3.71 (s,
3H), 3.50 (s, 3H), 3.40 (s, 3H); 13C NMR (150 MHz, CDCl3) δ
173.5, 167.0, 163.6, 163.3, 162.4, 152.2, 141.6, 139.4, 135.9, 134.8,
133.0, 132.2, 132.1, 131.5, 131.4, 130.3, 128.7, 127.7, 127.1, 125.1,
124.3, 124.0, 112.3, 109.2, 95.7, 69.9, 52.6, 52.5, 52.3, 52.1, 44.5; IR
(KBr) ν 3029, 2951, 2845, 1740, 1704, 1605, 1513, 1483, 1436, 1343,
1299, 1179, 1134, 1070, 1008, 954, 867, 823, 784 cm−1; HRMS (ESI-
TOF) calcd for C33H27BrN2NaO9 ([M + Na]+) 697.0792, found
697.0799.
Tetramethyl 1-benzyl-1′-phenyl-5-methyl-2-oxo-1′H-spiro-
[indoline-3,2′-pyridine]-3′,4′,5′,6′-tetracarboxylate (1h): yellow
1
solid, 0.427 g, 70%; mp 88−90 °C; H NMR (600 MHz, DMSO-
d6) δ 7.45−7.41 (m, 2H), 7.36 (t, J = 7.2 Hz, 1H), 7.19 (t, J = 7.2 Hz,
2H), 7.17−7.12 (m, 3H), 7.08 (d, J = 7.2 Hz, 1H), 6.66 (d, J = 7.2 Hz,
2H), 6.54 (d, J = 7.8 Hz, 1H), 6.32 (d, J = 7.8 Hz, 1H), 4.65 (d, J =
16.2 Hz, 1H), 4.40 (d, J = 16.2 Hz, 1H), 3.77 (s, 3H), 3.62 (s, 3H),
3.36 (s, 3H), 3.28 (s, 3H), 2.32 (s, 3H); 13C NMR (150 MHz, DMSO-
d6) δ 173.0, 166.2, 162.9, 162.8, 161.7, 152.2, 139.2, 138.6, 136.2,
135.2, 133.1, 131.8, 130.3, 130.1, 130.0, 129.9, 128.9, 128.4,
128.3(2C), 127.2, 126.9, 124.8, 112.0, 109.6, 94.2, 69.5, 52.6, 52.4,
52.1, 52.0, 43.3, 20.6; IR (KBr) ν 3006, 2951, 2852, 1744, 1606, 1495,
1437, 1345, 1313, 1238, 1151, 999, 820, 769 cm−1; HRMS (ESI-TOF)
calcd for C34H30N2NaO9 ([M + Na]+) 633.1844, found 633.1853.
Tetramethyl 1-benzyl-1′-(4-methylphenyl)-5-methyl-2-oxo-1′H-
spiro[indoline-3,2′-pyridine]-3′,4′,5′,6′-tetracarboxylate (1i): yellow
solid, 0.393 g, 63%; mp 182−184 °C; 1H NMR (600 MHz, CDCl3) δ
7.53 (s, 1H), 7.30−7.28 (m, 1H), 7.17 (t, J = 7.2 Hz, 1H), 7.12 (t, J =
7.2 Hz, 2H), 7.09 (d, J = 7.8 Hz, 1H), 7.01 (d, J = 7.8 Hz, 1H), 6.76
(d, J = 7.8 Hz, 1H), 6.67 (d, J = 7.2 Hz, 2H), 6.33 (d, J = 7.8 Hz, 1H),
6.23−6.21 (m, 1H), 4.76 (d, J = 15.6 Hz, 1H), 4.24 (d, J = 15.6 Hz,
1H), 3.89 (s, 3H), 3.71 (s, 3H), 3.48 (s, 3H), 3.37 (s, 3H), 2.35 (s,
3H), 2.31 (s, 3H); 13C NMR (150 MHz, CDCl3) δ 173.7, 167.4,
163.4, 162.7, 153.0, 139.9, 139.7, 139.3, 135.1, 134.3, 133.6, 131.6,
131.0, 130.8, 130.3, 129.4, 128.6, 127.3, 127.1, 125.7, 111.6, 109.1,
94.7, 70.2, 52.5, 52.2, 52.0, 44.4, 21.4, 21.1; IR (KBr) ν 3058, 2989,
2949, 1725, 1608, 1502, 1439, 1350, 1305, 1243, 1198, 1149, 1007,
963, 900, 813 cm−1; HRMS (ESI-TOF) calcd for C35H32N2NaO9 ([M
+ Na]+) 647.2000, found 647.2004.
Tetramethyl 1-benzyl-1′-(4-methoxyphenyl)-5-methyl-2-oxo-
1′H-spiro[indoline-3,2′-pyridine]-3′,4′,5′,6′-tetracarboxylate (1j):
1
yellow solid, 0.397 g, 62%; mp 198−200 °C; H NMR (600 MHz,
Tetramethyl 1-benzyl-1′-(4-tert-butylphenyl)-5-chloro-2-oxo-
DMSO-d6) δ 7.43 (s, 1H), 7.19 (t, J = 7.2 Hz, 1H), 7.14−7.11 (m,
4H), 6.89 (d, J = 7.2 Hz, 1H), 6.67 (d, J = 7.2 Hz, 2H), 6.61−6.56 (m,
2H), 6.19 (d, J = 7.2 Hz, 1H), 4.73 (d, J = 15.6 Hz, 1H), 4.39 (d, J =
15.6 Hz, 1H), 3.77 (s, 3H), 3.71 (s, 3H), 3.62 (s, 3H), 3.38 (s, 3H),
3.32 (s, 3H), 2.32 (s, 3H); 13C NMR (150 MHz, DMSO-d6) δ 173.1,
166.3, 162.8, 161.8, 160.0, 152.8, 139.2, 138.7, 135.2, 133.0, 131.8,
131.7, 131.3, 130.0, 128.7, 128.1, 127.2, 126.9, 124.7, 113.7, 111.7,
109.6, 93.9, 69.7, 55.3, 52.6, 52.3, 52.1, 51.9, 43.3, 20.6; IR (KBr) ν
3003, 2950, 2840, 1724, 1608, 1501, 1437, 1350, 1437, 1350, 1306,
1245, 1200, 1151, 1030, 1007, 961, 825 cm−1; HRMS (ESI-TOF)
calcd for C35H32N2NaO10 ([M + Na]+) 663.1949, found 663.1941.
Tetramethyl 1-benzyl-1′-(4-tert-butylphenyl)-5-methyl-2-oxo-
1′H-spiro[indoline-3,2′-pyridine]-3′,4′,5′,6′-tetracarboxylate (1k):
1′H-spiro[indoline-3,2′-pyridine]-3′,4′,5′,6′-tetracarboxylate (1o):
1
yellow solid, 0.412 g, 60%; mp 106−108 °C; H NMR (600 MHz,
DMSO-d6) δ 7.68 (s, 1H), 7.42 (d, J = 7.8 Hz, 1H), 7.36 (d, J = 8.4
Hz, 1H), 7.23−7.17 (m, 4H), 7.10 (d, J = 7.2 Hz, 1H), 6.88 (d, J = 7.2
Hz, 2H), 6.71 (d, J = 8.4 Hz, 1H), 6.39 (d, J = 7.8 Hz, 1H), 4.68 (d, J
= 15.6 Hz, 1H), 4.46 (d, J = 15.6 Hz, 1H), 3.78(s, 3H), 3.62 (s, 3H),
3.38 (s, 3H), 3.25 (s, 3H), 1.21 (s, 9H); 13C NMR (150 MHz, CDCl3)
δ 173.5, 166.9, 163.5, 163.3, 162.3, 153.4, 152.9, 140.5, 140.1, 134.7,
134.1, 132.2, 131.1, 130.9, 129.9, 129.0, 128.7, 127.6, 127.1, 125.8,
125.3, 124.7, 111.2, 110.6, 95.2, 70.0, 52.4, 52.3(2C), 52.0, 44.8, 34.8,
31.2; IR (KBr) ν 2955, 1746, 1701, 1608, 1504, 1435, 1344, 1312,
1234, 1141, 1018, 956, 878, 823, 787 cm−1; HRMS (ESI-TOF) calcd
for C37H35ClN2NaO9 ([M + Na]+) 709.1923, found 709.1909.
1
yellow solid, 0.453g, 68%; mp 164−166 °C; H NMR (600 MHz,
4134
dx.doi.org/10.1021/jo500144z | J. Org. Chem. 2014, 79, 4131−4136

The Journal of Organic Chemistry
Note
Tetramethyl 1-benzyl-1′-(4-chlorophenyl)-5-chloro-2-oxo-1′H-
spiro[indoline-3,2′-pyridine]-3′,4′,5′,6′-tetracarboxylate (1p): yellow
solid, 0.332 g, 50%; mp 146−148 °C; 1H NMR (600 MHz, CDCl3) δ
7.68 (s, 1H), 7.35 (d, J = 8.4 Hz, 1H), 7.29 (s, 1H), 7.23−7.22 (m,
4H), 6.96 (d, J = 8.4 Hz, 1H), 6.65 (d, J = 4.2 Hz, 2H), 6.43 (d, J = 8.4
Hz, 1H), 6.32 (d, J = 8.4 Hz, 1H), 4.84 (d, J = 15.6 Hz, 1H), 4.25 (d, J
= 15.6 Hz, 1H), 3.89 (s, 3H), 3.72 (s, 3H), 3.54 (s, 3H), 3.41 (s, 3H);
13C NMR (150 MHz, CDCl3) δ 173.2, 166.8, 163.4, 163.2, 162.2,
152.2, 140.3, 139.8, 136.3, 135.1, 134.3, 132.8, 131.8, 131.6, 131.5,
129.4, 129.2, 128.7, 128.5, 127.8, 127.0, 125.4, 111.7, 110.6, 95.7, 69.9,
52.8, 52.6, 52.5, 52.2, 44.6; IR (KBr) ν 3005, 2952, 2849, 1744, 1701,
1606, 1513, 1484, 1435, 1348, 1297, 1246, 1138, 1092, 1014, 956, 888,
821, 787 cm−1; HRMS (ESI-TOF) calcd for C33H26Cl2N2NaO9 ([M +
Na]+) 687.0909, found 687.0917.
Tetramethyl 2-oxo-1′-(4-methoxyphenyl)-1′H-spiro[indoline-
3,4′-pyridine]-2′,3′,5′,6′-tetracarboxylate (2b): yellow solid, 0.295
g, 55%; mp 243−245 °C; 1H NMR (600 MHz, DMSO-d6) δ 10.46 (s,
1H), 7.29 (d, J = 9.0 Hz, 2H), 7.26 (d, J = 7.2 Hz, 1H), 7.20 (t, J = 7.2
Hz, 1H), 7.00 (d, J = 9.0 Hz, 2H), 6.97 (t, J = 7.2 Hz, 1H), 6.78 (d, J =
7.8 Hz, 1H), 3.79 (s, 3H), 3.39 (s, 6H), 3.35 (s, 6H); 13C NMR (150
MHz, DMSO-d6) δ 178.9, 163.8, 162.3, 159.9, 142.4(2C), 135.3,
131.1, 129.1, 129.0, 123.8, 121.7, 114.1, 108.9, 106.3, 55.5, 52.6, 51.8,
49.6; IR (KBr) ν 3195, 3089, 3035, 2956, 2901, 2846, 1716, 1621,
1582, 1511, 1469, 1440, 1330, 1294, 1290, 1152, 1084, 1020, 986, 947,
900, 867, 833 cm−1; HRMS (ESI-TOF) calcd for C27H24N2NaO10
([M + Na]+) 559.1323, found 559.1316.
Tetramethyl 2-oxo-1′-(4-ethoxyphenyl)-1′H-spiro[indoline-3,4′-
pyridine]-2′,3′,5′,6′-tetracarboxylate (2c): yellow solid, 0.303 g,
55%; mp 228−230 °C; 1H NMR (600 MHz, CDCl3) δ 7.89 (s,
1H), 7.34−7.30 (m, 3H), 7.21 (t, J = 7.2 Hz, 1H), 7.04 (t, J = 7.2 Hz,
1H), 6.86−6.82 (m, 3H), 4.05−4.01 (m, 2H), 3.44 (s, 12H), 1.43 (t, J
= 7.2 Hz, 3H); 13C NMR (150 MHz, CDCl3) δ 180.1, 164.5, 162.9,
159.8, 143.4, 141.1, 135.9, 131.7, 129.3, 129.0, 124.6, 122.5, 114.3,
109.0, 105.7, 63.8, 52.5, 51.8, 50.3, 14.6; IR (KBr) ν 3214, 3094, 3035,
2954, 2886, 2845, 1716, 1618, 1584, 1510, 1473, 1439, 1394, 1330,
1294, 1240, 1192, 1151, 1084, 1040, 986, 935, 900, 867, 834 cm−1;
HRMS (ESI-TOF) calcd for C28H26N2NaO10 ([M + Na]+) 573.1480,
found 573.1493.
Tetraethyl 1-benzyl-1′-phenyl-5-methyl-2-oxo-1′H-spiro-
[indoline-3,2′-pyridine]-3′,4′,5′,6′-tetracarboxylate (1q:). yellow
1
solid, 0.366 g, 55%; mp 64−66 °C; H NMR (600 MHz, CDCl3) δ
7.58 (s, 1H), 7.45 (d, J = 7.2 Hz, 1H), 7.31−7.28 (m, 2H), 7.16 (t, J =
7.2 Hz, 2H), 7.11 (t, J = 7.2 Hz, 2H), 7.00 (d, J = 7.8 Hz, 1H), 6.95 (t,
J = 7.2 Hz, 1H), 6.58 (d, J = 7.8 Hz, 2H), 6.37 (d, J = 7.2 Hz, 1H),
6.29 (d, J = 8.4 Hz, 1H), 4.77 (d, J = 15.6 Hz, 1H), 4.38−4.31 (m,
2H), 4.24−4.16 (m, 3H), 4.07−4.01 (m, 1H), 3.95−3.90 (m, 1H),
3.82−3.74 (m, 2H), 2.36 (s, 3H), 1.38 (s, J = 7.2 Hz, 3H), 1.25 (t, J =
7.2 Hz, 3H), 1.04 (t, J = 7.2 Hz, 3H), 0.88 (t, J = 7.2 Hz, 3H); 13C
NMR (150 MHz, CDCl3) δ 173.8, 166.7, 163.4, 163.1, 162.2, 152.3,
139.6, 137.1, 135.1, 133.4, 131.7, 131.4, 131.0(2C), 129.6, 128.7,
128.5, 127.9, 127.3, 127.0, 125.8, 112.2, 109.0, 95.3, 70.4, 61.9, 61.4,
61.1, 60.7, 44.4, 21.1, 14.0, 13.9, 13.7, 13.3; IR (KBr) ν 2983, 1739,
1606 1495, 1410, 1372, 1334, 1303, 1232, 1195, 1026, 857, 806, 769
cm−1; HRMS (ESI-TOF) calcd for C38H38N2NaO9 ([M + Na]+)
689.2470, found 689.2477.
Tetramethyl 1-benzyl-5-methyl-2-oxo-1′-phenyl-1′H-spiro-
[indoline-3,4′-pyridine]-2′,3′,5′,6′-tetracarboxylate (2d): yellow
1
solid, 0.293 g, 48%; mp 86−88 °C; H NMR (600 MHz, CDCl3) δ
7.56 (d, J = 7.2 Hz, 2H), 7.48 (d, J = 7.2 Hz, 1H), 7.44 (d, J = 8.4 Hz,
1H), 7.41 (s, 2H), 7.35 (t, J = 7.2 Hz, 3H), 7.28(s, 1H), 7.15 (s, 1H),
6.97 (d, J = 7.8 Hz, 1H), 6.65 (d, J = 7.8 Hz, 1H), 4.92 (s, 2H), 3.40
(s, 6H), 3.20 (s, 6H), 2.30 (s, 3H); 13C NMR (150 MHz, CDCl3) δ
178.1, 164.6, 163.0, 143.0, 141.2, 136.5, 135.3, 132.2, 130.4, 130.0,
129.2, 128.9, 128.7, 128.6, 128.5, 128.2, 127.6, 125.3, 114.1, 108.3,
107.6, 106.3, 52.5, 51.8, 49.8, 45.1, 21.1; IR (KBr) ν 3025, 2952, 1717,
1591, 1494, 1438, 1325, 1288, 1232, 1194, 1145, 1086, 982, 853, 814
cm−1; HRMS (ESI-TOF) calcd for C34H30N2NaO9 ([M + Na]+)
633.1844, found 633.1836.
Tetraethyl 1-benzyl-1′-(4-methylphenyl)-5-chloro-2-oxo-1′H-
spiro[indoline-3,2′-pyridine]-3′,4′,5′,6′-tetracarboxylate (1r): yellow
1
solid, 0.503 g, 72%; mp 80−82 °C; H NMR (600 MHz, CDCl3) δ
7.73 (d, J = 7.8 Hz, 1H), 7.31−7.29 (m, 1H), 7.20−7.17 (m, 2H), 7.13
(t, J = 7.2 Hz, 2H), 7.08 (d, J = 8.4 Hz, 1H), 6.79 (d, J = 7.2 Hz, 1H),
6.61 (d, J = 7.2 Hz, 2H), 6.33 (d, J = 8.4 Hz, 1H), 6.30−6.29 (m, 1H),
4.85 (d, J = 16.2 Hz, 1H), 4.37−4.30 (m, 2H), 4.24−4.16 (m, 3H),
4.08−4.03 (m, 1H), 3.98−3.93 (m, 1H), 3.83−3.77 (m, 2H), 2.31 (s,
3H), 1.38 (s, J = 7.2 Hz, 3H), 1.25 (t, J = 7.2 Hz, 3H), 1.08 (t, J = 7.2
Hz, 3H), 0.92 (t, J = 7.2 Hz, 3H); 13C NMR (150 MHz, CDCl3) δ
173.6, 166.4, 163.2, 163.0, 161.9, 152.5, 140.5, 140.1, 140.0, 134.6,
134.3, 132.4, 131.3, 131.0, 130.5, 129.4, 128.8, 128.6, 128.4, 127.5,
127.1, 125.5, 111.5, 110.3, 95.3, 70.2, 62.0, 61.5, 61.3, 60.8, 44.6, 21.3,
14.0, 13.9, 13.7, 13.3; IR (KBr) ν 2983, 1741, 1701, 1607, 1502, 1410,
1372, 1334, 1303, 1229, 1192, 1140, 1025, 859, 815, 785 cm−1; HRMS
(ESI-TOF) calcd for C38H37ClN2NaO9 ([M + Na]+) 723.2080, found
723.2078.
Tetramethyl 1-benzyl-5-methyl-2-oxo-1′-(4-methoxyphenyl)-
1′H-spiro[indoline-3,4′-pyridine]-2′,3′,5′,6′-tetracarboxylate (2e:).
1
yellow solid, 0.340 g, 53%; mp 228−230 °C; H NMR (600 MHz,
CDCl3) δ 7.55 (d, J = 7.2 Hz, 2H), 7.36−7.33 (m, 4H), 7.27 (d, J = 7.8
Hz, 1H), 7.13 (s, 1H), 6.96 (d, J = 7.8 Hz, 1H), 6.86 (d, J = 9.0 Hz,
2H), 6.63 (d, J = 7.8 Hz, 1H), 4.91 (s, 2H), 3.81 (s, 3H), 3.44 (s, 6H),
3.20 (s, 6H), 2.29 (s, 3H); 13C NMR (150 MHz, CDCl3) δ 178.1,
164.6, 163.1, 160.3, 143.4, 141.3, 136.6, 135.4, 132.1, 131.8, 129.7,
129.2, 128.6, 128.5, 127.6, 125.3, 113.9, 107.6, 106.2, 55.5, 52.5, 51.8,
49.8, 45.1, 21.1; IR (KBr) ν 3007, 2949, 2843, 1748, 1715, 1641, 1583,
1502, 1439, 1363, 1329, 1290, 1239, 1193, 1142, 1088, 1020, 982, 954,
898, 859, 801 cm−1; HRMS (ESI-TOF) calcd for C35H32N2NaO10
([M + Na]+) 663.1949, found 663.1938.
2. General Procedure for the Preparation of Spiro[indoline-
3,4′-pyridine]tetracarboxylates 2a−e from One-Pot Reactions
of Arylamine, Dimethyl Acetylenedicarboxylate, and Isatins.
To a stirred solution of arylamine (1.0 mmol), dimethyl
acetylenedicarboxylate (2.0 mmol), and isatin (1.0 mmol) in
methylene dichloride (10.0 mL), BF3·OEt2 (0.5 mmol) was added at
room temperature. Then the mixture was refluxed for about 1 day.
Then the solvent was removed by evaporation and the residue was
subjected to preparative thin-layer chromatography (25 × 15 cm SiO2
plate) with a mixture of light petroleum and ethyl acetate (V/V = 1:1)
as developing reagent to give the pure products 2a−e for analysis.
Tetramethyl 2-oxo-1′-(4-methylpheny)-1′H-spiro[indoline-3,4′-
pyridine]-2′,3′,5′,6′-tetracarboxylate (2a): yellow solid, 0.234 g,
45%; mp 228−230 °C; 1H NMR (600 MHz, CDCl3) δ 7.63 (s,
1H), 7.35 (d, J = 7.2 Hz, 1H), 7.28 (d, J = 8.4 Hz, 2H), 7.22 (t, J = 7.2
Hz, 1H), 7.18 (d, J = 8.4 Hz, 2H), 7.05 (t, J = 7.8 Hz, 1H), 6.82 (d, J =
7.8 Hz, 1H), 3.44 (s, 6H), 3.42 (s, 6H), 2.37 (s, 3H); 13C NMR (150
MHz, CDCl3) δ 179.8, 164.5, 162.9, 143.2, 140.8, 140.3, 135.8, 134.4,
130.0, 129.5, 129.1, 124.8, 122.7, 108.8, 105.6, 52.5, 51.9, 50.2, 21.3; IR
(KBr) ν 3204, 3094, 2952, 1752, 1718, 1617, 1582, 1507, 1472, 1439,
1328, 1291, 1234, 1195, 1149, 981, 861 cm−1; HRMS (ESI-TOF)
calcd for C27H24N2NaO9 ([M + Na]+) 543.1374, found 543.1368.
ASSOCIATED CONTENT
■
S
* Supporting Information
1H and 13C NMR spectra for all new compounds. This material
is available free of charge via the Internet at http://pubs.acs.
org/. Crystallographic data for 1e (CCDC 979514), 1k
(CCDC 979515), and 2b (CCDC 979516) been deposited
at the Cambridge Crystallographic Database Centre. These data
can be obtained free of charge via www.ccdc.ac.ck./data_
request/cif.
AUTHOR INFORMATION
■
Corresponding Author
*Tel: 86-514-8797531. Fax: 86-514-87975244. E-mail: cgyan@
yzu.edu.cn.
Notes
The authors declare no competing financial interest.
4135
dx.doi.org/10.1021/jo500144z | J. Org. Chem. 2014, 79, 4131−4136

The Journal of Organic Chemistry
Note
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ACKNOWLEDGMENTS
■
This work was financially supported by the National Natural
Science Foundation of China (Grant No. 21272200) and the
Priority Academic Program Development of Jiangsu Higher
Education Institutions. We also thank the Analysis and Test
Center of Yangzhou University providing instruments for
analysis.
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