Efficient synthesis of bulky 4-substituted-isatins via microwave-promoted Suzuki cross-coupling reaction

Article abstract of DOI:10.1016/j.tetlet.2012.12.021

Indoline-2,3-diones (isatins) and their derivatives are important heterocycles found in nature and present in numerous bioactive compounds. Very few examples related to the synthesis of 4-substituted-arylisatins have been reported before. Utilizing microwave irradiation, the synthesis of bulky 4-substituted-arylisatins via a Suzuki cross-coupling has been developed with a wide range of substrates. All the reactions proceeded smoothly and afforded moderate to excellent yields of products, which indicating that electronic effects and steric modifications have little effect on this reaction.

Full text of DOI:10.1016/j.tetlet.2012.12.021

Tetrahedron Letters 54 (2013) 949–955
Contents lists available at SciVerse ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Efficient synthesis of bulky 4-substituted-isatins via microwave-promoted
Suzuki cross-coupling reaction
⇑
⇑
Yu-Chao Liu, Chen-Jin Ye, Qiong Chen , Guang-Fu Yang
Key Laboratory of Pesticide & Chemical Biology, Ministry of Education, College of Chemistry, Central China Normal University, 152 Luoyu Road, Wuhan, Hubei 430079, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Indoline-2,3-diones (isatins) and their derivatives are important heterocycles found in nature and present
in numerous bioactive compounds. Very few examples related to the synthesis of 4-substituted-arylisa-
tins have been reported before. Utilizing microwave irradiation, the synthesis of bulky 4-substituted-ary-
lisatins via a Suzuki cross-coupling has been developed with a wide range of substrates. All the reactions
proceeded smoothly and afforded moderate to excellent yields of products, which indicating that elec-
tronic effects and steric modifications have little effect on this reaction.
Received 19 October 2012
Revised 30 November 2012
Accepted 7 December 2012
Available online 17 December 2012
Keywords:
Ó 2012 Elsevier Ltd. All rights reserved.
4-(Het)arylisatins
Suzuki cross-coupling reactions
Steric effect
Electronic effect
Microwave irradiation
Introduction
harsh reaction conditions, narrow range of substrates, and poor
yields. Recently, modern synthetic protocols for the syntheses of
Indoline-2,3-diones (isatins) and their derivatives are important
heterocycles found in nature and present in numerous bioactive
compounds which can act as inhibitors of apoptosis,1a,b anticonvul-
sants,1c and other antiviral,1d,e anti-bacterial, and anti-fungal
agents.1f For example, as shown in Figure 1 and 5-(30-methylb-
uten-20-yl)isatin and 6-(30-methylbuten-20-yl)isatin, isolated
respectively from Chaetomium globosum and Streptomyces albus,
have been described as novel antifungal compounds.2 Indirubin
is the active ingredient of Danggui Longhui Wan, a mixture of
plants that is used in traditional Chinese medicine to treat chronic
diseases. It is also found in Chinese medicinal herbs Isatis indigotica
and Strobilanthes cusia.3 Methisazone and the b-thiosemicarbazone
of N-methyl isatin (IBT) have also been described as smallpox che-
moprophylactic agents.1d,3a In addition, the isatins are broadly
used as an important intermediate in organic synthesis and techni-
cal supramolecular applications.4,5
Two traditional methods have been developed for the synthesis
of isatins.4,6–9 The first one involves a strong acid- or base-medi-
ated condensation of aniline with diethyl ketomalonate,6 oxalyl
chloride,7 or chloral hydrate.8 The other method involves the
functionalization of preexisting aromatic rings.9 Although these
approaches provided useful access to substituted indoline-
2,3-diones, they suffered from some drawbacks, such as relatively
isatin and its derivatives have been established, including C–H oxi-
dation/acylation of formyl-N-arylformamides10a and Suzuki cross-
coupling reaction from iodoisatins.10b However, these methods
could be used to synthesize only 5-, 6-, or 7-substituted-isa-
tins,10b–h and very few examples related to the synthesis of 4-
substituted-isatins could be found.10b Thus, the development of
an efficient method to prepare 4-substituted-isatins is of great
interest.
Microwave irradiation has emerged as a powerful technique for
promoting a variety of chemical reactions.11 The main benefits of
performing reactions under microwave irradiation conditions are
significant enhancements in rate and higher product yields. During
recent years, we have developed some new methods for efficient
synthesis of heterocyclic compounds under microwave irradia-
tion.12 Herein, as a continuation of our research on the synthesis
of structurally diverse heterocyclic compounds, we report the syn-
thesis of isatin derivatives bearing bulky substituents on position-4
via a Suzuki cross-coupling under microwave irradiation.
Result and discussion
The 4-iodoindoline-2,3-dione derivatives were prepared by
using a previously reported synthetic strategy.13 Then, the reaction
between 4-iodoindoline-2,3-dione (1) and phenylboronic acid (3a)
was selected as a model to optimize the conditions for the palla-
dium-catalyzed cross-coupling reaction. As shown in Table 1, as
compared to the conventional heating methods, microwave
⇑
Corresponding authors. Tel.: +86 27 67867800; fax: +86 27 67867141.
E-mail addresses: qchen@mail.ccnu.edu.cn (Q. Chen), gfyang@ccnu.edu.cn (G.-F.
Yang).
0040-4039/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2012.12.021

950
Y.-C. Liu et al. / Tetrahedron Letters 54 (2013) 949–955
O
O
O
4
7
3
5
6
R
2
O
O
O
N
N
1
N
H
H
H
Indoline-2,3-diones (isatins)
5-(3'-methylbuten-2'-yl) isatin
6-(3'-methylbuten-2'-yl) isatin
H
H
OH
O
N
NH2
N
NH2
N
N
NH
S
S
N
O
O
H
N
N
H
Indirubin
Methisazone
IBT
Figure 1. Pharmacologically active indoline-2,3-diones (isatins) and their derivatives.
irradiation can dramatically accelerate the reactions and increase
the reaction yields. In addition, the temperature showed a marked
effect on the reaction. The yield was notably increased to 92% when
the reaction was carried out at 130 °C under microwave irradiation
(Table 1, entries 2, 3 and 5).
Next, we investigated the effect of the stoichiometric ratio of
the reactants was investigated. If the ratio of 4-iodoindoline-2,3-
dione to phenylboronic acid was decreased from 1:1.2 to 1:1, it
was necessary to increase the reaction temperature to maintain
shorter reaction time and higher yields (Table 1, entries 3–6). Fur-
thermore, the presence of the Pd(PPh3)4 catalyst was critical to the
reaction and without it, no reaction was observed. For the base
additive, NaHCO3 was more effective than K2CO3 (Table 1, entries
6–10).
With the optimized conditions defined, the substrate scope was
further investigated by employing a variety of arylboronic acids
substituted with electron-donating and electron-withdrawing
groups. As shown in Table 2, significant structural variations in
the arylboronic acid components were well tolerated and afforded
the corresponding 4-substituted-isatins in moderate to good
yields. Both electron-rich and electron-poor aryl boronic acids
could be successfully utilized in this transformation. Even poten-
tially problematic groups, such as nitro and trifluoromethyl, did
not show significant effects on the transformation and afforded
acceptable to moderate yields of products (Table 2, 14 and 15). It
should be noted that incorporation of halogen-substituents at the
ortho, meta or para positions in arylboronic acids did not retard
the reaction, demonstrating that steric modification can be accom-
plished without compromising the efficiency of the process (Ta-
ble 2, 5–7 and 11–13). More importantly, the reaction proved to
be tolerant of valuable but unstable substituents, such as formyl
and acetyl (Table 2, compounds 17 and 18).
Very promisingly, polysubstituted phenylboronic acids, furan-
2-ylboronic acid, thiophen-2-ylboronic acid, dibenzofuran-4-ylbo-
ronic acid, naphthalen-1-ylboronic acid, and benzofuran-2-ylbo-
ronic acid also reacted with 4-iodoindoline-2,3-dione very well
and gave moderate to excellent yields of products (Table 2, 19–31).
In order to investigate the effects of steric hindrance on the
reaction, the reaction between 4-iodo-5-methylindoline-2,3-dione
and various boronic acids was examined. As shown in Table 2
(compounds 32–39), all the reaction proceeded smoothly and
afforded moderate to excellent yields of products, which indicating
that the ortho-methyl has little steric effect on the cross-coupling
reaction.
Finally, we also extended the substrates to alkyl and alkenyl
boronic acids. Not surprisingly, the process showed good
functional group compatibility for the alkenyl reagents (Table 2,
compounds 40–42). However, alkyl reagents did not reacted with
4-iodoindoline-2,3-diones under the investigated conditions.
Table 1
Optimization of the reaction conditionsa
Conclusion
I
O
B(OH)2
Ph
O
In summary, we have developed a convenient method for the
synthesis of bulky 4-substituted-isatins from 4-iodoisatins by
using microwave-assisted Suzuki cross-coupling reactions. The
reaction is applicable to a wide range of substrates and produces
a variety of densely functionalized bulky 4-substituted-isatins in
good to excellent yields within a very short time.
+
O
O
N
N
H
H
1
3a
4
Entry
Temp (°C)
1:3a
Catalyst
Base
Time
98 h
Yieldb (%)
1
2
3
4
5
6
7
8
9
10
110c
1:1.2
1:1.2
1:1.2
1:1
1:1.2
1:1
1:1
1:1
1:1
1:1
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
None
NaHCO3
NaHCO3
NaHCO3
NaHCO3
NaHCO3
NaHCO3
Na2CO3
K2CO3
32
54
71
67
92
92
73
59
dMW:110
MW:120
MW:120
MW:130
MW:130
MW:130
MW:130
MW:130
MW:130
65 min
6 min
20 min
3 min
5 min
5 min
5 min
5 min
5 min
Experimental section
General information
Unless otherwise noted, materials were purchased from com-
mercial suppliers and used without further purification. All the sol-
vents were treated according to general methods. Flash column
chromatography (FC) was performed using 200–300 mesh silica
gel.
NaHCO3
None
No reaction
No reaction
Pd(PPh3)4
a
Unless otherwise noted, all the reactions were carried out at 0.2 mmol scale in
the solution of DME (3 mL) and H2O (0.6 mL) with 5 mol % of Pd(PPh3)4, 2 equiv of
base, protected by N2.
1H NMR spectra were recorded on 400/600 (400/600 MHz)
spectrophotometers. Chemical shifts (d) are reported in ppm from
the solvent resonance as the internal standard (CDCl3: 7.26 ppm,
DMSO: 2.50 ppm). Data are reported as follows: chemical shift,
b
Isolated yields.
c
Conventional heating method.
Microwave irradiation.
d

Y.-C. Liu et al. / Tetrahedron Letters 54 (2013) 949–955
951
Table 2
The reaction with various arylboronic acid and 4-iodoisatina
I
R'
O
O
B(OH)2
R
Ar
Pd(PPh3)4 (5 mol%)
R
or
O
+
O
Alkenyl boronic acids
N
H
NaHCO3 (2eq)
DME/H2O = 5:1 (v/v)
MW(130°C), 4~12min
N
H
1
3
. R = H
2. R = CH3
4~39
R = CH3, H
R' = Ar or alkenyl
F
F
Br
F
O
O
O
O
O
O
O
O
O
O
N
N
N
H
O
H
H
O
N
H
N
H
N
4
7
6
H
5
8
5min, 92%
7min, 70%
10min, 89%
9
5min, 84%
6min, 85%
12 min, 94%
CF3
Cl
Cl
NO2
Cl
O
O
O
O
O
O
O
O
O
N
H
O
N
O
O
H
N
H
N
H
N
N
H
H
13
12
10
11
14
15
5min, 70%
9min, 80%
7min, 88%
8min, 84%
8min, 45%
5min, 74%
OCH3
H
O
O
F
Cl
Cl
F
Cl
O
O
O
O
O
O
O
O
N
H
O
O
O
O
N
H
N
N
H
N
H
N
H
H
20
5min, 83%
16
19
21
17
18
5min, 85%
6min, 78%
5min, 82%
6min, 55%
Cl
6min, 82%
F
F
F3C
CF3
O
OCH3
Ph
S
H3CO
OCH3
O
O
F
O
O
O
O
O
O
N
H
N
H
N
H
O
O
O
N
H
N
H
N
27
H
22
24
6min, 69%
23
25
26
6min, 78%
7min, 68%
6min, 95%
6min, 70%
5min, 81%
F
O
O
O
O
O
O
O
O
O
O
O
O
O
N
H
N
H
N
H
O
O
N
N
H
N
H
28
H
30
7min, 96%
32
29
5min, 69%
33
31
5min, 95%
5min, 95%
5min, 80%
6min, 91%
OCH3
Cl
Br
NO2
O
O
O
O
O
O
O
O
O
O
O
O
N
H
N
H
N
N
N
H
N
H
H
H
36
34
35
37
6min, 77%
38
39
5min, 81%
5min, 85%
6min, 83%
6min, 57%
5min, 90%
O
O
O
N
H
O
O
O
N
H
41
4min, 20%b
N
H
40
42
5min, 82%
5min, 93%
a
Unless otherwise noted, all the reactions were carried out at 0.2 mmol scale in the solution of DME (3 mL) and H2O (0.6 mL) with 5 mol % of Pd(PPh3)4, 2 equiv of NaHCO3,
protected by N2.
b
Reacted with vinylboronic acid pinacol ester.

952
Y.-C. Liu et al. / Tetrahedron Letters 54 (2013) 949–955
multiplicity (s = singlet, d = doublet, t = triplet, m = multiplet,
q = quaternary), coupling constants (Hz) and integration. 13C
NMR spectra were recorded on 400/600 (100/150 MHz) spectro-
photometers (CDCl3: 77.0 ppm, DMSO: 39.5 ppm) with complete
proton decoupling. Mass spectra were measured on a Trace MS
spectrometer. Elemental analysis was determined on an elemen-
tary analysis instrument.
4-(2-Fluorophenyl)indoline-2,3-dione (7)
Orange solid, 30.8 mg, 70% yield; mp: 196–197 °C. 1H NMR
(400 MHz, dmso) d 11.20 (s, 1H), 7.65 (t, J = 8.0 Hz, 1H), 7.54–
7.41 (m, 2H), 7.30 (dd, J = 15.6, 8.4 Hz, 2H), 7.01 (d, J = 7.6 Hz,
1H), 6.96 (d, J = 8.0 Hz, 1H). 13C NMR (100 MHz, dmso) d 182.89,
160.39, 158.85, 157.93, 151.11, 138.02, 134.13, 131.17, 130.81,
130.72, 124.76, 124.36, 124.32, 124.21, 115.57, 115.36, 115.00,
111.89. MS: m/z = 241.06 (M+). Anal. Calcd for (C14H8FNO2): C,
69.71; H, 3.34; N, 5.81. Found: C, 69.78; H, 3.20; N, 5.71.
General procedure for the synthesis of compounds 4–39
4-Iodoisatin
0.183 mmol) were dissolved in DME (3 mL) and H2O (0.6 mL) in a
microwave vial under nitrogen atmosphere. Pd(PPh3)4
(5 mmol %, 11 mg) and sodium bicarbonate (30.7 mg, 0.366 mmol)
were added, and the reaction mixture was irradiated in a micro-
wave apparatus at 130 °C for 4–12 min. After the reaction mixture
was cooled to ambient temperature, the product was concentrated,
and the crude mixture was purified by silica gel column chroma-
tography using petroleum ether/acetone (20/1 to 10/1) as eluent
to give the title compound 4.
1
(50.0 mg, 0.183 mmol) and 3a (22.3 mg,
4-(4-Bromophenyl)indoline-2,3-dione (8)
Orange solid, 46.9 mg, 85% yield; mp: 287–288 °C. 1H NMR
(400 MHz, dmso) d 11.15 (s, 1H), 7.69–7.57 (m, 3H), 7.54–7.47
(m, 2H), 7.01 (d, J = 7.6 Hz, 1H), 6.91 (d, J = 8.0 Hz, 1H). 13C NMR
a
(100 MHz, dmso)
d 182.93, 159.01, 151.45, 139.95, 137.91,
135.47, 131.00, 130.98, 124.04, 122.20, 114.18, 111.44. MS: m/
z = 301.11 (M+). Anal. Calcd for (C14H8BrNO2): C, 55.66; H, 2.67;
N, 4.64. Found: C, 55.63; H, 2.81; N, 4.47.
4-(4-(tert-Butyl)phenyl)indoline-2,3-dione (9)
Orange solid, 48.0 mg, 94% yield; mp: 245–246 °C. 1H NMR
(400 MHz, dmso) d 11.12 (s, 1H), 7.59 (t, J = 7.6 Hz, 1H), 7.48 (q,
J = 8.0 Hz, 4H), 7.01 (d, J = 7.6 Hz, 1H), 6.87 (d, J = 7.6 Hz, 1H),
1.33 (s, 9H). 13C NMR (100 MHz, dmso) d 182.97, 159.01, 151.50,
151.19, 141.53, 137.84, 133.45, 128.60, 124.83, 124.34, 114.08,
110.83, 34.43, 31.07. MS: m/z =279.13 (M+). Anal. Calcd for
(C18H17NO2): C, 77.40; H, 6.13; N, 5.01. Found: C, 77.20; H, 6.23;
N, 5.19.
4-Iodoindoline-2,3-dione (1)
Orange solid, mp: 255–256 °C. 1H NMR (400 MHz, dmso) d
11.10 (s, 1H), 7.48 (d, J = 8.0 Hz, 1H), 7.26 (t, J = 8.0 Hz, 1H), 6.91
(d, J = 8.0 Hz, 1H). 13C NMR (100 MHz, dmso) d 182.87, 158.71,
152.74, 138.47, 133.20, 119.17, 111.77, 93.10. MS: m/z = 272.94
(M+). Anal. Calcd for (C8H4INO2): C, 35.19; H, 1.48; N, 5.13. Found:
C, 35.21; H, 1.32; N, 5.10.
4-Iodo-5-methylindoline-2,3-dione (2)
4-(p-Tolyl)indoline-2,3-dione (10)
Orange solid, mp: 230–231 °C. 1H NMR (400 MHz, dmso) d
10.96 (s, 1H), 7.46 (d, J = 8.0 Hz, 1H), 6.81 (d, J = 8.0 Hz, 1H), 2.33
(s, 3H). 13C NMR (100 MHz, dmso) d 183.09, 158.58, 150.77,
137.66, 135.88, 119.56, 111.58, 99.45, 25.86. MS: m/z = 286.95
(M+). Anal. Calcd for (C9H6INO2): C, 37.66; H, 2.11; N, 4.88. Found:
C, 37.67; H, 2.25; N, 4.80.
Orange solid, 38.1 mg, 88% yield; mp: 190–191 °C. 1H NMR
(400 MHz, dmso) d 11.11 (s, 1H), 7.59 (t, J = 8.0 Hz, 1H), 7.44 (d,
J = 8.0 Hz, 2H), 7.25 (d, J = 7.9 Hz, 2H), 6.99 (d, J = 7.7 Hz, 1H),
6.86 (d, J = 7.7 Hz, 1H), 2.37 (s, 3H). 13C NMR (100 MHz, dmso) d
182.99, 159.05, 151.49, 141.65, 138.20, 137.83, 133.44, 128.77,
128.64, 124.23, 114.10, 110.81, 20.89.MS: m/z = 237.07 (M+). Anal.
Calcd for (C15H11NO2): C, 75.94; H, 4.67; N, 5.90. Found: C, 75.78;
H, 4.78; N, 5.94.
4-Phenylindoline-2,3-dione (4)
Orange solid, 37.5 mg, 92% yield; mp: 215–216 °C. 1H NMR
(400 MHz, dmso) d 11.13 (s, 1H), 7.61 (t, J = 8.0 Hz, 1H), 7.54 (s,
2H), 7.45 (d, J = 4.8 Hz, 3H), 7.02 (d, J = 8.0 Hz, 1H), 6.89 (d,
J = 8.0 Hz, 1H). 13C NMR (100 MHz, dmso) d 182.97, 159.03,
151.48, 141.49, 137.86, 136.33,128.85, 128.62, 128.04, 124.33,
114.20, 111.09. MS: m/z = 223.07 (M+). Anal. Calcd for
(C14H9NO2): C, 75.33; H, 4.06; N, 6.27. Found: C, 75.26; H, 4.19;
N, 6.52.
4-(4-Chlorophenyl)indoline-2,3-dione (11)
Orange solid, 39.6 mg, 84% yield; mp: 285–286 °C. 1H NMR
(400 MHz, dmso) d 11.14 (s, 1H), 7.60 (dd, J = 18.4, 8.4 Hz, 3H),
7.52 (d, J = 8.4 Hz, 2H), 7.01 (d, J = 8.0 Hz, 1H), 6.91 (d, J = 8.0 Hz,
1H). 13C NMR (100 MHz, dmso) d 182.94, 159.01, 151.45, 139.93,
137.91, 135.10, 133.50, 130.70, 128.08, 124.10, 114.22, 111.43.
MS: m/z = 257.05 (M+). Anal. Calcd for (C14H8ClNO2): C, 65.26; H,
3.13; N, 5.44. Found: C, 65.17; H, 2.94; N, 5.17.
4-(4-Fluzorophenyl)indoline-2,3-dione (5)
Orange solid, 37.0 mg, 84% yield; mp: 289–290 °C. 1H NMR
(400 MHz, dmso) d 11.13 (s, 1H), 7.60 (dd, J = 8.0, 6.0 Hz, 3H), 7.29
4-(3-Chlorophenyl)indoline-2,3-dione (12)
Orange solid, 37.7 mg, 80% yield; mp: 303–304 °C. 1H NMR
(400 MHz, dmso) d 11.14 (s, 1H), 7.65–7.58 (m, 2H), 7.50 (m,
3H), 7.04 (d, J = 8.0 Hz, 1H), 6.92 (d, J = 8.0 Hz, 1H). 13C NMR
(100 MHz, dmso) d182.90, 159.00, 151.40, 139.49, 138.33, 137.87,
132.67, 129.97, 128.70, 128.42, 127.42, 124.14, 114.33, 111.66.
MS: m/z = 257.03 (M+). Anal. Calcd for (C14H8ClNO2): C, 65.26; H,
3.13; N, 5.44. Found: C, 65.11; H, 3.19; N, 5.46.
(t, J = 8.0 Hz, 2H), 7.01 (d, J = 7.6 Hz, 1H), 6.89 (d, J = 8.0 Hz, 1H). 13
C
NMR (100 MHz, dmso) d 182.97, 163.64, 161.19, 159.04, 151.41,
140.25, 137.86, 132.65, 131.12, 131.03, 124.20, 115.06, 114.85,
114.24, 111.14. MS: m/z = 241.16 (M+). Anal. Calcd for (C14H8FNO2):
C, 69.71; H, 3.34; N, 5.81. Found: C, 69.69; H, 3.52; N, 5.79.
4-(3-Fluorophenyl)indoline-2,3-dione (6)
Orange solid, 39.2 mg, 89% yield; mp: 263–264 °C. 1H NMR
(400 MHz, dmso) d 11.14 (s, 1H), 7.62 (t, J = 8.0 Hz, 1H), 7.50 (dd,
J = 14.0, 8.0 Hz, 1H), 7.39 (t, J = 10.0 Hz, 2H), 7.28 (dd, J = 12.8,
4.4 Hz, 1H), 7.04 (d, J = 7.6 Hz, 1H), 6.92 (d, J = 7.6 Hz, 1H). 13C
NMR (100 MHz, dmso) d 182.88, 162.93, 160.52, 159.00, 151.45,
139.75, 138.64, 138.57, 137.89, 130.11, 130.03, 124.89, 124.17,
115.96, 115.74, 115.49, 114.32, 111.63. MS: m/z = 241.04 (M+).
Anal. Calcd for (C14H8FNO2): C, 69.71; H, 3.34; N, 5.81. Found: C,
69.83; H, 3.06; N, 5.97.
4-(2-Chlorophenyl)indoline-2,3-dione (13)
Orange solid, 33.0 mg, 70% yield; mp: 219–220 °C. 1H NMR
(400 MHz, dmso) d 11.21 (s, 1H), 7.65 (t, J = 8.0 Hz, 1H), 7.56 (d,
J = 8.0 Hz, 1H), 7.48–7.32 (m, 3H), 6.95 (dd, J = 13.6, 8.0 Hz, 2H).
13C NMR (100 MHz, dmso) d 182.95, 158.84, 150.89, 137.92,
137.64, 135.63, 131.69, 131.02, 129.97, 129.26, 126.98, 124.68,
115.17, 111.90. MS: m/z = 257.04 (M+). Anal. Calcd for
(C14H8ClNO2): C, 65.26; H, 3.13; N, 5.44. Found: C, 65.50; H, 3.06;
N, 5.42.

Y.-C. Liu et al. / Tetrahedron Letters 54 (2013) 949–955
953
4-(4-Nitrophenyl)indoline-2,3-dione (14)
137.77, 133.68, 127.94, 127.54, 124.01, 114.42, 112.17. MS: m/
z = 291.11 (M+). Anal. Calcd for (C14H7Cl2NO2): C, 57.56; H, 2.42;
N, 4.79. Found: C, 57.79; H, 2.34; N, 4.91.
Orange solid, 22.0 mg, 45% yield; mp: 307–308 °C. 1H NMR
(400 MHz, dmso) d 11.19 (s, 1H), 8.30 (d, J = 8.8 Hz, 2H), 7.83 (d,
J = 8.8 Hz, 2H), 7.67 (t, J = 8.0 Hz, 1H), 7.08 (d, J = 8.0 Hz, 1H), 6.99
(d, J = 8.0 Hz, 1H). 13C NMR (100 MHz, dmso) d 182.85, 158.97,
151.50, 147.38, 142.93, 138.58, 137.99, 130.28, 124.13, 123.15,
114.42, 112.39. MS: m/z = 268.05 (M+). Anal. Calcd for
(C14H8N2O4): C, 62.69; H, 3.01; N, 10.44. Found: C, 62.77; H,
3.10; N, 10.20.
4-(3-Chloro-4-fluorophenyl)indoline-2,3-dione (21)
Orange solid, 41.3 mg, 82% yield; mp: 266–267 °C. 1H NMR
(400 MHz, dmso) d 11.15 (s, 1H), 7.80 (dd, J = 7.2, 2.0 Hz, 1H),
7.66–7.45 (m, 3H), 7.04 (d, J = 7.6 Hz, 1H), 6.92 (d, J = 8.0 Hz, 1H).
13C NMR (100 MHz, dmso) d 182.92, 159.01, 158.61, 156.15,
151.38, 138.57, 137.86, 133.90, 133.86, 131.07, 129.61, 129.54,
124.09, 119.22, 119.05, 116.68, 116.47, 114.30, 111.68. MS: m/
z = 275.01 (M+). Anal. Calcd for (C14H7ClFNO2): C, 61.00; H, 2.56;
N, 5.08. Found: C, 60.90; H, 2.42; N, 5.09.
4-(4-(Trifluoromethyl)phenyl)indoline-2,3-dione (15)
Orange solid, 39.4 mg, 74% yield; mp: 264–265 °C.1H NMR
(400 MHz, dmso) d 11.17 (s, 1H), 7.79 (dd, J = 23.4, 8.4 Hz, 4H),
7.65 (t, J = 8.0 Hz, 1H), 7.06 (d, J = 7.6 Hz, 1H), 6.96 (d, J = 8.0 Hz,
1H). 13C NMR (100 MHz, dmso) d 182.91, 158.98, 151.49, 140.40,
139.45, 137.96, 129.70, 128.99, 128.68, 125.60, 124.92, 124.88,
124.19, 122.89, 114.36, 111.95. MS: m/z = 291.18 (M+). Anal. Calcd
for (C15H8F3NO2): C, 61.86; H, 2.77; N, 4.81. Found: C, 61.81; H,
2.50; N, 4.95.
4-(3,5-Difluorophenyl)indoline-2,3-dione (22)
Orange solid, 45.0 mg, 95% yield; mp: 290–291 °C. 1H NMR
(400 MHz, dmso) d 11.17 (s, 1H), 7.62 (t, J = 8.0 Hz, 1H), 7.37–
7.24 (m, 3H), 7.07 (d, J = 8.0 Hz, 1H), 6.95 (d, J = 8.0 Hz, 1H). 13C
NMR (100 MHz, dmso) d 182.76, 163.25, 163.12, 160.81, 160.68,
158.95, 151.42, 139.71, 138.38, 137.89, 124.02, 114.39, 112.36,
112.11. MS: m/z = 259.05 (M+). Anal. Calcd for (C14H7F2NO2): C,
64.87; H, 2.72; N, 5.40. Found: C, 64.68; H, 2.67; N, 5.66.
4-(4-Methoxyphenyl)indoline-2,3-dione (16)
Orange solid, 39.3 mg, 85% yield; mp: 209–210 °C. 1H NMR
(400 MHz, dmso) d 11.10 (s, 1H), 7.57 (t, J = 8.0 Hz, 1H), 7.52 (d,
J = 8.4 Hz, 2H), 7.01 (d, J = 8.4 Hz, 3H), 6.83 (d, J = 7.6 Hz, 1H),
3.82 (s, 3H). 13C NMR (100 MHz, dmso) d 182.98, 159.78, 159.10,
151.45, 141.46, 137.78, 130.31, 128.51, 124.11, 113.98, 113.48,
110.42, 55.20. MS: m/z = 253.10 (M+). Anal. Calcd for
(C15H11NO3): C, 71.14; H, 4.38; N, 5.53. Found: C, 71.02; H, 4.53;
N, 5.30.
4-(4-Chloro-2-fluorophenyl)indoline-2,3-dione (23)
Orange solid, 35.3 mg, 70% yield; mp: 250–251 °C. 1H NMR
(400 MHz, dmso) d 11.21 (s, 1H), 7.66 (t, J = 8.0 Hz, 1H), 7.56 (d,
J = 10.0 Hz, 1H), 7.49 (t, J = 8.0 Hz, 1H), 7.39 (d, J = 8.4 Hz, 1H), 7.00
(dd, J = 16.0, 8.0 Hz, 2H). 13C NMR (100 MHz, dmso) d 182.88,
163.69, 160.32, 158.82, 157.82, 151.15, 138.07, 134.33, 134.23,
132.81, 132.42, 124.57, 123.39, 123.23, 116.27, 116.01, 114.94,
112.20. MS: m/z = 275.03 (M+). Anal. Calcd for (C14H7ClFNO2): C,
61.00; H, 2.56; N, 5.08. Found: C, 61.21; H, 2.36; N, 4.99.
4-(2,3-Dioxoindolin-4-yl)benzaldehyde (17)
Orange solid, 25.3 mg, 55% yield; mp: 273–274 °C. 1H NMR
(400 MHz, dmso) d 11.17 (s, 1H), 10.08 (s, 1H), 7.98 (d, J = 8.0 Hz,
2H), 7.77 (d, J = 8.0 Hz, 2H), 7.65 (t, J = 8.0 Hz, 1H), 7.07 (d,
J = 7.6 Hz, 1H), 6.96 (d, J = 8.0 Hz, 1H). 13C NMR (100 MHz, dmso)
d 192.84, 182.89, 158.98, 151.52, 142.18, 139.81, 137.94, 135.89,
129.67, 129.15, 124.18, 114.36, 111.98. MS: m/z = 251.08 (M+).
Anal. Calcd for (C15H9NO3): C, 71.71; H, 3.61; N, 5.58. Found: C,
71.68; H, 3.56; N, 5.47.
4-(3,5-Bis(trifluoromethyl)phenyl)indoline-2,3-dione (24)
Orange solid, 45.3 mg, 69% yield; mp: 232–233 °C. 1H NMR
(400 MHz, dmso) d 11.20 (s, 1H), 8.26 (s, 2H), 8.18 (s, 1H), 7.66
(s, 1H), 7.18 (d, J = 8.0 Hz, 1H), 6.99 (d, J = 8.0 Hz, 1H). 13C NMR
(100 MHz, dmso)
d 182.93, 159.12, 151.42, 138.53, 137.93,
137.27, 130.59, 130.27, 129.94, 129.78, 129.61, 127.40, 124.69,
124.17, 121.97, 119.26, 114.56, 112.55. MS: m/z = 359.06 (M+).
Anal. Calcd for (C16H7F6NO2): C, 53.50; H, 1.96; N, 3.90. Found: C,
53.24; H, 1.97; N, 3.98.
4-(4-Acetylphenyl)indoline-2,3-dione (18)
Orange solid, 39.7 mg, 82% yield; mp: 247–248 °C. 1H NMR
(400 MHz, dmso) d 11.16 (s, 1H), 8.02 (d, J = 8.4 Hz, 2H), 7.72–
7.57 (m, 3H), 7.06 (d, J = 8.0 Hz, 1H), 6.94 (d, J = 8.0 Hz, 1H), 2.64
(s, 3H). 13C NMR (100 MHz, dmso) d 197.63, 182.90, 158.98,
151.50, 140.86, 140.01, 137.90, 136.54, 129.18, 127.89, 124.17,
114.32, 111.80, 26.84. MS: m/z = 265.08 (M+). Anal. Calcd for
(C16H11NO3): C, 72.45; H, 4.18; N, 5.28. Found: C, 72.52; H, 4.27;
N, 5.14.
4-(3,4,5-Trimethoxyphenyl)indoline-2,3-dione (25)
Orange solid, 46.4 mg, 81% yield; mp: 238–239 °C. 1H NMR
(400 MHz, dmso) d 11.12 (s, 1H), 7.58 (t, J = 8.0 Hz, 1H), 7.11 (d,
J = 8.0 Hz, 1H), 6.90 (s, 2H), 6.87 (d, J = 8.0 Hz, 1H), 3.81 (s, 6H),
3.73 (s, 3H). 13C NMR (100 MHz, dmso) d 182.83, 159.03, 152.40,
151.44, 141.54, 137.96, 137.63, 131.54, 124.16, 114.22, 110.91,
106.56, 60.05, 55.94. MS: m/z = 313.12 (M+). Anal. Calcd for
(C17H15NO5): C, 65.17; H, 4.83; N, 4.47. Found: C, 65.36; H, 4.73;
N, 4.57.
4-(4-Fluoro-3-methylphenyl)indoline-2,3-dione (19)
Orange solid, 36.4 mg, 78% yield; mp: 243–244 °C.1H NMR
(400 MHz, dmso) d 11.13 (s, 1H), 7.59 (t, J = 8.0 Hz, 1H), 7.47 (d,
J = 7.2 Hz, 1H), 7.40 (d, J = 5.2 Hz, 1H), 7.21 (t, J = 9.2 Hz, 1H), 7.00
(d, J = 7.6 Hz, 1H), 6.88 (d, J = 8.0 Hz, 1H), 2.28 (s, 3H). 13C NMR
4-([1,10-Biphenyl]-4-yl)indoline-2,3-dione (26)
Orange solid, 42.7 mg, 78% yield; mp: 283–284 °C. 1H NMR
(400 MHz, dmso) d 11.15 (s, 1H), 7.76 (d, J = 8.0 Hz, 4H), 7.64 (dd,
J = 16.4, 8.0 Hz, 3H), 7.51 (t, J = 7.6 Hz, 2H), 7.40 (t, J = 7.2 Hz, 1H),
7.08 (d, J = 8.0 Hz, 1H), 6.91 (d, J = 8.0 Hz, 1H). 13C NMR (100 MHz,
dmso) d 183.00, 159.06, 151.53, 141.02, 140.32, 139.53, 137.89,
135.40, 129.51, 129.01, 127.72, 126.70, 126.28, 124.24, 114.22,
111.14. MS: m/z = 299.10 (M+). Anal. Calcd for (C20H13NO2): C,
80.25; H, 4.38; N, 4.68. Found: C, 80.13; H, 4.22; N, 4.78.
(100 MHz, dmso)
d 182.97, 162.19, 159.75, 159.02, 151.43,
140.53, 137.82, 132.36, 132.21, 128.42, 128.34, 124.20, 123.93,
123.76, 114.66, 114.44, 114.17, 111.05, 14.16. MS: m/z = 255.08
(M+). Anal. Calcd for (C15H10FNO2): C, 70.58; H, 3.95; N, 5.49.
Found: C, 70.70; H, 3.68; N, 5.43.
4-(3,5-Dichlorophenyl)indoline-2,3-dione (20)
Orange solid, 44.3 mg, 83% yield; mp: 310–311 °C. 1H NMR
(400 MHz, dmso) d 11.16 (s, 1H), 7.69 (s, 1H), 7.66–7.57 (m, 3H),
7.07 (d, J = 7.8 Hz, 1H), 6.94 (d, J = 7.8 Hz, 1H). 13C NMR
4-(Thiophen-2-yl)indoline-2,3-dione (27)
Red solid, 28.5 mg, 68% yield; mp: 180–181 °C. 1H NMR
(400 MHz, dmso) d 11.16 (s, 1H), 7.98 (d, J = 3.2 Hz, 1H), 7.74 (d,
(100 MHz, dmso)
d 182.81, 158.96, 151.34, 139.59, 137.86,

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Y.-C. Liu et al. / Tetrahedron Letters 54 (2013) 949–955
J = 4.8 Hz, 1H), 7.58 (t, J = 8.0 Hz, 1H), 7.22 (d, J = 7.2 Hz, 2H), 6.84
(d, J = 7.6 Hz, 1H). 13C NMR (100 MHz, dmso) d 182.57, 158.70,
151.89, 138.22, 138.16, 133.88, 129.65, 128.48, 128.07, 123.29,
113.04, 110.98.MS: m/z = 229.04 (M+). Anal. Calcd for
(C12H7NO2S): C, 62.87; H, 3.08; N, 6.11; S, 13.99. Found: C, 63.01;
H, 3.21; N, 5.82; S, 13.73.
114.77, 111.24, 18.61. MS: m/z = 255.06 (M+). Anal. Calcd for
(C15H10FNO2): C, 70.58; H, 3.95; N, 5.49. Found: C, 70.71; H, 3.83;
N, 5.71.
4-(4-Methoxyphenyl)-5-methylindoline-2,3-dione (34)
Orange solid, 41.5 mg, 85% yield; mp: 189–190 °C. 1H NMR
(400 MHz, dmso) d 11.00 (s, 1H), 7.46 (d, J = 8.0 Hz, 1H), 7.18 (d,
J = 8.4 Hz, 2H), 6.99 (d, J = 8.4 Hz, 2H), 6.80 (d, J = 8.0 Hz, 1H),
3.82 (s, 3H), 2.02 (s, 3H). 13C NMR (100 MHz, dmso) d 183.37,
159.06, 158.80, 149.14, 140.53, 139.13, 130.59, 130.23, 127.60,
115.36, 113.32, 110.76, 55.01, 18.81. MS: m/z = 267.11 (M+). Anal.
Calcd for (C16H13NO3): C, 71.90; H, 4.90; N, 5.24. Found: C, 71.91;
H, 5.01; N, 5.32.
4-(Furan-2-yl)indoline-2,3-dione (28)
Red solid, 26.9 mg, 69% yield; mp: 237–238 °C. 1H NMR
(400 MHz, dmso) d 11.16 (s, 1H), 7.95 (d, J = 3.6 Hz, 1H), 7.91 (s,
1H), 7.63 (t, J = 8.0 Hz, 1H), 7.48 (d, J = 8.0 Hz, 1H), 6.82 (d,
J = 7.6 Hz, 1H), 6.73 (dd, J = 3.2, 1.6 Hz, 1H). 13C NMR (100 MHz,
dmso) d 182.23, 158.62, 151.62, 149.23, 144.65, 138.28, 129.02,
119.23, 114.11, 112.48, 111.40, 110.62. MS: m/z = 213.08 (M+).
Anal. Calcd for (C12H7NO3): C, 67.61; H, 3.31; N, 6.57. Found: C,
67.75; H, 3.48; N, 6.62.
4-(4-Chlorophenyl)-5-methylindoline-2,3-dione (35)
Orange solid, 41.2 mg, 83% yield; mp: 259–260 °C. 1H NMR
(400 MHz, dmso) d 11.02 (s, 1H), 7.50 (d, J = 8.4 Hz, 3H), 7.28 (d,
J = 8.4 Hz, 2H), 6.84 (d, J = 8.0 Hz, 1H), 2.00 (s, 3H). 13C NMR
4-(Dibenzo[b,d]furan-4-yl)indoline-2,3-dione (29)
Orange solid, 54.4 mg, 95% yield; mp: 289–290 °C. 1H NMR
(400 MHz, dmso) d 11.29 (s, 1H), 8.23 (dd, J = 9.6, 8.4 Hz, 2H),
7.74 (d, J = 8.0 Hz, 1H), 7.65 (d, J = 8.4 Hz, 1H), 7.59 (d, J = 7.6 Hz,
1H), 7.51 (dt, J = 9.6, 8.0 Hz, 2H), 7.44 (t, J = 7.6 Hz, 1H), 7.26 (d,
J = 7.6 Hz, 1H), 7.04 (d, J = 8.0 Hz, 1H). 13C NMR (100 MHz, dmso)
d 182.79, 158.93, 155.38, 152.88, 151.34, 138.12, 135.11, 128.12,
127.70, 124.88, 123.74, 123.47, 123.22, 122.93, 121.56, 121.24,
121.16, 115.05, 111.91, 111.74. MS: m/z = 313.07 (M+). Anal. Calcd
for (C20H11NO3): C, 76.67; H, 3.54; N, 4.47. Found: C, 76.45; H, 3.43;
N, 4.19.
(100 MHz, dmso) d 183.34, 158.99, 149.11, 139.25, 138.98,
134.51, 132.59, 130.77, 130.19, 128.04, 115.25, 111.41, 18.55.
MS: m/z = 271.07 (M+). Anal. Calcd for (C15H10ClNO2): C, 66.31;
H, 3.71; N, 5.16. Found: C, 66.53; H, 3.62; N, 5.10.
5-Methyl-4-(p-tolyl)indoline-2,3-dione (36)
Orange solid, 37.2 mg, 81% yield; mp: 221–222 °C. 1H NMR
(400 MHz, dmso) d 10.99 (s, 1H), 7.48 (d, J = 8.0 Hz, 1H), 7.24 (d,
J = 7.6 Hz, 2H), 7.12 (d, J = 7.6 Hz, 2H), 6.81 (d, J = 8.0 Hz, 1H),
2.38 (s, 3H), 2.00 (s, 3H). 13C NMR (100 MHz, dmso) d 183.35,
159.00, 149.11, 140.69, 139.13, 136.91, 132.70, 130.43, 128.67,
128.55, 115.28, 110.91, 20.90, 18.74. MS: m/z = 251.11 (M+). Anal.
Calcd for (C16H13NO2): C, 76.48; H, 5.21; N, 5.57. Found: C, 76.59;
H, 5.19; N, 5.86.
4-(Naphthalen-2-yl)indoline-2,3-dione (30)
Orange solid, 48.0 mg, 96% yield; mp: 264–265 °C. 1H NMR
(400 MHz, dmso) d 11.17 (s, 1H), 8.11 (s, 1H), 7.98 (d, J = 8.0 Hz,
3H), 7.67 (dd, J = 14.8, 7.2 Hz, 2H), 7.61–7.52 (m, 2H), 7.15 (d,
J = 8.0 Hz, 1H), 6.94 (d, J = 8.0 Hz, 1H). 13C NMR (100 MHz, dmso)
d 183.04, 159.11, 151.54, 141.38, 137.91, 134.00, 132.81, 132.62,
128.32, 127.90, 127.54, 127.27, 126.94, 126.69, 126.35, 124.56,
114.43, 111.20. MS: m/z = 273.10 (M+). Anal. Calcd for
(C18H11NO2): C, 79.11; H, 4.06; N, 5.13. Found: C, 79.34; H, 4.16;
N, 4.87.
4-(4-Bromophenyl)-5-methylindoline-2,3-dione (37)
Orange solid, 44.5 mg, 77% yield; mp: 255–256 °C. 1H NMR
(400 MHz, dmso) d 11.02 (s, 1H), 7.63 (d, J = 8.4 Hz, 2H), 7.50 (d,
J = 8.0 Hz, 1H), 7.22 (d, J = 8.4 Hz, 2H), 6.84 (d, J = 8.0 Hz, 1H),
2.00 (s, 3H). 13C NMR (100 MHz, dmso) d 183.32, 158.98, 149.09,
139.25, 138.97, 134.89, 131.07, 130.95, 130.10, 121.24, 115.19,
111.40, 18.56. MS: m/z = 315.05 (M+). Anal. Calcd for
(C15H10BrNO2): C, 56.99; H, 3.19; N, 4.43. Found: C, 56.88; H,
2.97; N, 4.32.
4-(Benzofuran-2-yl)indoline-2,3-dione (31)
Red solid, 43.8 mg, 91% yield; mp: 314–315 °C. 1H NMR
(400 MHz, dmso) d 11.23 (s, 1H), 8.37 (s, 1H), 7.83 (d, J = 7.6 Hz,
1H), 7.77–7.63 (m, 3H), 7.43 (t, J = 7.6 Hz, 1H), 7.32 (t, J = 7.6 Hz,
1H), 6.94 (d, J = 6.8 Hz, 1H). 13C NMR (100 MHz, dmso) d 182.29,
158.50, 153.99, 152.10, 150.85, 138.35, 128.63, 128.27, 126.28,
123.48, 122.29, 120.39, 112.63, 112.13, 111.16, 109.59. MS: m/
z = 263.09 (M+). Anal. Calcd for (C16H9NO3): C, 73.00; H, 3.45; N,
5.32. Found: C, 72.99; H, 3.38; N, 5.36.
5-Methyl-4-(4-nitrophenyl)indoline-2,3-dione (38)
Orange solid, 29.4 mg, 57% yield; mp: 239–240 °C.1H NMR
(400 MHz, dmso) d 11.06 (s, 1H), 8.30 (d, J = 8.4 Hz, 2H), 7.56 (dd,
J = 12.8, 8.4 Hz, 3H), 6.90 (d, J = 8.0 Hz, 1H), 2.01 (s, 3H). 13C NMR
(100 MHz, dmso)
d 183.26, 158.97, 149.14, 147.04, 142.91,
139.41, 137.79, 130.49, 129.81, 123.13, 115.11, 112.05, 18.41.
MS: m/z = 282.08 (M+). Anal. Calcd for (C15H10N2O4): C, 63.83; H,
3.57; N, 9.92. Found: C, 63.71; H, 3.79; N, 9.73.
5-Methyl-4-phenylindoline-2,3-dione (32)
Orange solid, 41.2 mg, 95% yield; mp: 206–207 °C. 1H NMR
(400 MHz, dmso) d 11.01 (s, 1H), 7.49 (d, J = 8.0 Hz, 1H), 7.43 (d,
J = 7.2 Hz, 3H), 7.24 (d, J = 6.4 Hz, 2H), 6.83 (d, J = 7.6 Hz, 1H),
2.00 (s, 3H). 13C NMR (100 MHz, dmso) d 183.34, 158.99, 149.08,
140.52, 139.17, 135.71, 130.29, 128.71, 127.96, 127.71, 115.25,
111.10, 18.67. MS: m/z = 237.09 (M+). Anal. Calcd for
(C15H11NO2): C, 75.94; H, 4.67; N, 5.90. Found: C, 75.93; H, 4.57;
N, 6.03.
5-Methyl-4-(naphthalen-2-yl)indoline-2,3-dione (39)
Orange solid, 47.3 mg, 90% yield; mp: 210–211 °C.1H NMR
(400 MHz, dmso) d 11.04 (s, 1H), 7.98 (t, J = 6.8 Hz, 2H), 7.92 (d,
J = 7.2 Hz, 1H), 7.80 (s, 1H), 7.62–7.50 (m, 3H), 7.38 (d, J = 8.4 Hz,
1H), 6.87 (d, J = 8.0 Hz, 1H), 2.05 (s, 3H). 13C NMR (100 MHz, dmso)
d 183.43, 160.33, 159.05, 149.16, 140.35, 139.25, 133.34, 132.65,
132.37, 130.47, 128.01, 127.64, 127.34, 126.96, 126.29, 126.16,
115.44, 111.22, 18.71. MS: m/z = 287.13 (M+). Anal. Calcd for
(C19H13NO2): C, 79.43; H, 4.56; N, 4.88. Found: C, 79.20; H, 4.71;
N, 4.73.
4-(4-Fluorophenyl)-5-methylindoline-2,3-dione (33)
Orange solid, 37.3 mg, 80% yield; mp: 241–242 °C. 1H NMR
(400 MHz, dmso) d 11.01 (s, 1H), 7.50 (d, J = 7.2 Hz, 1H), 7.28 (d,
J = 8.8 Hz, 4H), 6.83 (d, J = 6.8 Hz, 1H), 2.01 (s, 3H). 13C NMR
(E)-4-(Pent-1-en-1-yl)indoline-2,3-dione (40)
(101 MHz, dmso)
d
183.36, 162.97, 160.54, 159.00, 149.09,
Orange solid, 33.8 mg, 82% yield; mp: 158–159 °C. 1H NMR
(600 MHz, dmso) d 11.04 (s, 1H), 7.46 (t, J = 7.8 Hz, 1H), 7.32 (d,
139.37, 139.20, 131.85, 131.04, 130.95, 130.37, 115.38, 114.98,

Y.-C. Liu et al. / Tetrahedron Letters 54 (2013) 949–955
955
Breinholt, J.; Demuth, H.; Heide, M.; Jensen, G. W.; Moller, I. L.; Nielsen, R. I.;
Olsen, C. E.; Rosendahl, C. N. Acta Chem. Scand. 1996, 50, 443–445.
J = 8.4 Hz, 1H), 7.20 (d, J = 16.2 Hz, 1H), 6.73–6.65 (m, 2H), 2.23 (q,
J = 7.2 Hz, 2H), 1.48 (dd, J = 14.4, 7.2 Hz, 2H), 0.93 (t, J = 7.2 Hz, 3H).
13C NMR (150 MHz, dmso) d 184.62, 159.04, 150.47, 137.83,
137.70, 137.67, 123.90, 118.62, 113.39, 109.90, 34.89, 21.73,
13.62. MS: m/z = 215.06 (M+). Anal. Calcd for (C13H13NO2): C,
72.54; H, 6.09; N, 6.51. Found: C, 72.57; H, 6.04; N, 6.72.
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M.; Matsuda, H.; Kubo, M. Chem. Pharm. Bull. 1998, 46, 886–888; (b) Gil-
Turners, M. S.; Hay, M. E.; Fenical, W. Science 1989, 246, 116–118; (c)
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6313–6316; (e) Franz, A. K.; Dreyfuss, P. D.; Schreiber, S. L. J. Am. Chem. Soc.
2007, 129, 1020–1021; (f) Matos, M. A. R.; Margarida, S. M.; Victor, M. F. M.;
Joel, F. L. Org. Biomol. Chem. 2003, 1, 2566–2571; (g) Dirk, B.; Jan, H. P.
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Jocelyn, W. J. Org. Chem. 2008, 73, 9151–9154; (i) Parvathaneni, S. P.; Keesara,
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4-Vinylindoline-2,3-dione (41)
Orange solid, 6.3 mg, 20% yield; mp: 160–161 °C. 1H NMR
(600 MHz, dmso) d 11.06 (s, 1H), 7.52 (t, J = 7.8 Hz, 1H), 7.47 (dd,
J = 18.0, 11.4 Hz, 1H), 7.37 (d, J = 7.8 Hz, 1H), 6.79 (d, J = 7.8 Hz,
1H), 6.14 (d, J = 18.0 Hz, 1H), 5.59 (d, J = 10.8 Hz, 1H). 13C NMR
(100 MHz, dmso)
d 184.70, 158.96, 150.60, 137.83, 137.11,
130.64, 120.43, 118.59, 113.99, 111.03. MS: m/z = 173.01 (M+).
Anal. Calcd for (C10H7NO2): C, 69.36; H, 4.07; N, 8.09. Found: C,
69.45; H, 4.11; N,8.08.
(E)-4-Styrylindoline-2,3-dione (42)
Orange solid, 42.3 mg, 93% yield; mp: 230–231 °C. 1H NMR
(400 MHz, dmso) d 9.01 (s, 1H), 5.88 (d, J = 16.8 Hz, 1H), 5.57–
5.50 (m, 3H), 5.45 (dd, J = 6.8, 4.0 Hz, 2H), 5.37 (t, J = 7.6 Hz, 2H),
5.28 (t, J = 7.2 Hz, 1H), 4.68 (dd, J = 5.6, 2.8 Hz, 1H). 13C NMR
6. (a) Guyot, A.; Martinet J. Compt. Rend. 1913, 166, 1625; (b) Martinet J. Compt.
Rend. 1918, 166, 851–853; (c) Bonnefoy, J.; Martinet J. Compt. Rend. 1921, 172,
220.
(100 MHz, dmso)
d 184.69, 159.08, 150.65, 137.73, 137.37,
´
´
7. (a) Stolle, R. J. Prakt. Chem. 1922, 104, 137; (b) Stolle, R.; Ber, B. D. Chemistry
1913, 46, 3915.
136.22, 134.26, 129.00, 128.91, 127.11, 121.98, 118.75, 113.98,
110.52. MS: m/z = 287.13 (M+). Anal. Calcd for (C16H11NO2): C,
77.10; H, 4.45; N, 5.62. Found: C, 77.18; H, 4.38; N, 5.40.
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9. Yadav, J. S.; B.V. Subba, R. B. V.; Suresh, R. C.; Krishna, A. D. Synthesis 2007, 5,
693–696.
Acknowledgments
10. (a) Tang, B. X.; Song, R. J.; Wu, C. Y.; Liu, Y.; Zhou, M. B.; Wei, W. T.; Deng, G. B.;
Yin, D. L.; Li, J. H. J. Am. Chem. Soc. 2010, 132, 8900–8902; (b) Ge´rard, A. L.;
Vincent, L.; Sylvain, R. Tetrahedron 2005, 61, 6082–6087; (c) Smet, M.; Schacht,
E.; Dehaen, W. Angew. Chem., Int. Ed. 2002, 41, 4547–4550; (d) Martinez, F.;
Naarman, H. Synth. Met. 1990, 39, 195–203; (e) Vincent, L.; Max, R.; Sylvain, R. J.
Org. Chem. 2000, 65, 4193–4194; (f) Allan, B. G.; Paul, A. K. Chem. Commun.
2010, 46, 4076–4078; (g) Jan, H. P.; Dirk, B. J. Mater. Chem. 2010, 20, 2956–
2958; (h) Neelu, K.; Kristin, J.; Silvano, D.; Patricia, W. B.; Raymond, T. C.; Steve,
T.; Desirée, H. H. T.; James, C. K.; Cheryl, N. N.; Adam, S.; Ruth, Y. S.; Wang, Q. J.
Med. Chem. 2007, 50, 21–39.
The research was supported in part by the National Basic Re-
search Program of China (No. 2010CB126103), the NSFC (No.
20902034, 20925206 and 21172091), and the National Key Tech-
nologies R&D Program (2011BAE06B05).
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