A comparison of the photosensitized rearrangement and the Lewis-acid-catalyzed rearrangement of spirooxindole epoxides

Article abstract of DOI:10.1002/ejoc.201201020

Spirooxindole epoxides undergo smooth rearrangement either under photosensitization conditions or under Lewis acid catalysis to give different products. The photosensitized rearrangement of spirooxindole epoxides leads to 3-acyl-2-indolones, such as spiro

Full text of DOI:10.1002/ejoc.201201020

FULL PAPER
DOI: 10.1002/ejoc.201201020
A Comparison of the Photosensitized Rearrangement and the Lewis-Acid-
Catalyzed Rearrangement of Spirooxindole Epoxides
Lihong Wang,[a] Yibing Su,[b] Xinmin Xu,[a] and Wei Zhang*[a]
Keywords: Rearrangement / Photochemistry / Regioselectivity / Epoxides / Lewis acids / Nitrogen heterocycles
Spirooxindole epoxides undergo smooth rearrangement
either under photosensitization conditions or under Lewis
acid catalysis to give different products. The photosensitized
rearrangement of spirooxindole epoxides leads to 3-acyl-2-
indolones, such as spiro[cycloalkane-1,3Ј-indolin]-2,2Ј-di-
ones, by cleavage of the Cα–O bond followed by alkyl mi-
gration. The SnCl4-catalyzed rearrangement of spirooxindole
epoxides gives 4,4-dialkylquinolin-2,3-diones, such as spiro-
[cycloalkane-1,4Ј-quinolin]-2Ј,3Ј-diones, by cleavage of the
Cβ–O bond followed by aryl migration.
rearrangement, we found that reports about the rearrange-
ment of α,β-epoxy amides were rare,[13] and we found no
report in the literature about the rearrangement of spiroox-
indole epoxides in which both the aryl and acyl groups were
attached to the α-carbon of an epoxide. Recently, we re-
ported the synthesis of spiro[oxindole–furan] by the [3+2]
reaction of spiro epoxides derived from oxindoles under ir-
radiation.[14] Continuing from the synthesis of the spiroox-
indole, in this paper, we report the rearrangement of spiro-
oxindole epoxides under both photosensitization and Lewis
acid catalysis. It was found the regioselectivity of the two
rearrangements was different. Under photosensitization
conditions, 3-acyl-2-indolones, such as spiro[cycloalkane-
1,3Ј-indolin]-2,2Ј-diones (2), were obtained as the sole prod-
ucts, arising from the cleavage of Cα–O bond and subse-
quent migration of an alkyl group; otherwise, 4,4-dialk-
ylquinolin-2,3-diones, such as spiro[cycloalkane-1,4Ј-quin-
olin]-2Ј,3Ј-diones (3), were obtained as the sole products,
arising from the cleavage of Cβ–O bond and subsequent
migration of an aryl group under SnCl4 catalysis
(Scheme 1).
Introduction
Epoxides are one of the most important and versatile
precursors in organic synthesis, due to their ready availabil-
ity and the ease of their transformation into a wide variety
of functional groups.[1] The rearrangement of epoxides to
carbonyl compounds is a useful synthetic transformation,
and several procedures have been developed for this pur-
pose, for example, the Lewis-acid-catalyzed rearrange-
ment,[2] the Brønsted-acid-catalyzed rearrangement,[3] the
photochemical rearrangement,[4] the electrochemical re-
arrangement,[5] and so on. Of these methods, the Lewis-
acid-catalyzed rearrangement is the most popular, and it
has been studied extensively. Many Lewis acid catalysts
have been identified that catalyze the rearrangement of ep-
oxides with varying degrees of success in terms of regio-
selectivity and stereoselectivity, and these include
BF3·Et2O,[2a]
InCl3,[2b]
Bi(OTf)3,[2c]
Cu(BF4)2,[2d]
tetraphenylpor-
Er(OTf)3,[2e] CrTPP(OTf)2 (TPP
=
phyrin),[2f] SnCl4,[2g] Et2AlCl,[2h] LiClO4,[2i] and Au(PMe3)-
Cl.[2j] Epoxides bearing various substituents have been sub-
jected to the rearrangement, including, for example, aryl-
substituted epoxides,[6] 2,3-epoxy alcohols,[7] epoxy alk-
enes,[8] epoxy alkynes,[9] α,β-epoxy ketones,[10] steroidal ep-
oxides,[11] and terpene epoxides.[12] Despite the fact that so
many epoxides have been examined in the epoxide–ketone
[a] State Key Laboratory of Applied Organic Chemistry and
College of Chemistry and Chemical Engineering, Lanzhou
University,
Lanzhou 730000, P. R. China
E-mail: zhangwei6275@yahoo.com
Homepage: http://sklaoc.lzu.edu.cn/lzupage/2011/08/17/
N20110817004041.html
[b] Instrumental Analysis and Research Center, College of
Chemistry and Chemical Engineering, Lanzhou University,
Lanzhou 730000, P. R. China
Scheme 1. Photosensitized and SnCl4-catalyzed rearrangement of
spirooxindole epoxides.
Spirooxindoles are important structural motifs in biolo-
gically relevant compounds, including natural products and
pharmaceuticals, and have shown an extensive range of bio-
E-mail: suyb@lzu.edu.cn
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201201020.
6606
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2012, 6606–6611

The Rearrangement of Spirooxindole Epoxides
logical effects, including antibacterial, antifungal, anticon- and the results are listed in Table 1. All of the spirooxindole
vulsant, antiviral, and antiproliferative activities.[15] The spi- epoxides gave analogous 3-acyl-2-indolones products (i.e.,
roquinolinone scaffold is also found in alkaloids, and is im- 2a–e), except for 1f–h. The structures of the products were
portant as a characteristic building block for a series of sig- fully identified by 1H and 13C NMR spectroscopy, MS, and
nificant biologically active compounds.[16] Despite the large HRMS.
number of published synthetic routes to spirooxindole and
spiroquinolinone derivatives, there are only a few papers
that describe the synthesis of spiro[cycloalkane-1,3Ј-
indoline] (2) or spiro[cycloalkane-1,4Ј-quinoline] (3). Gen-
erally, two routes have been established to construct the
rings spiro-annulated with cycloalkanes at C-3 of 2-
indolones or at C-4 of 2-quinolinones. One is based on the
cyclization of spirocycloalkanes from functionalized 2-
indolones or 2-quinolinones,[17a,17b] for example, the intra-
molecular Ullmann coupling and Claisen rearrangement 5-
(2-iodioindol-3-yl)penten-3-ols to give spiro[cyclohexene-
1,3Ј-indol]-2Ј-ones.[17a] The other route is to construct oxin-
doles or quinolinones from functionalized cycloalk-
anes,[17c,17g] for example, the aza-oxa [3,3]-sigmatropic re-
arrangement of N-[(cyclohexylcarbonyl)oxy]-N-phenylcarb-
amic acid methyl ester and subsequent cyclocondensation
to give spiro[cyclohexane-1,3Ј-indol]-2Ј-one.[17c]
Table 1. Benzophenone-sensitized rearrangement reactions of spi-
ro[indoline-3,2Ј-oxiran]-2-ones 1a–h.
Entry Epoxide
R1 R2 R3 R4
t
Conv.[a] Product Yield[b]
[h] [%]
[%]
1
2
3
5
6
7
8
1a
1b
1c
1d
1e
1f
H
H
H
Br
CH3 CH3 CH3
CH3 CH3
Ph CH3 CH3
CH3 CH3 CH3
5
5
5
5
ca. 100
2a
2b
2c
2d
2e
–
93
90
96
94
91
–
H
ca. 100
ca. 100
95
NO2 CH3 CH3 CH3
CH3 CH3 CH3 CH3
H
20 98
5
20
ca. 100
0
1g
CH3
H
Ph
–
–
In this paper, we supply a new synthetic route to spiro[cy-
cloalkane-1,3Ј-indol]-2,2Ј-diones by constructing spirocy-
cloalkyl units from spirooxindole epoxides, and to spiro[cy-
cloalkane-1,4Ј-quinolin]-2Ј,3Ј-diones by constructing spiro-
quinolinyl units from spirocycloalkane epoxides.
[a] Conversion was calculated on the basis of substrate 1a–h.
[b] Yield of isolated products was based on consumed substrates
1a–e.
From a comparison of the structures of the epoxide start-
ing materials (i.e., 1a–e) and the products (i.e., 2a–e), it
could be seen that the benzophenone-sensitized ring-open-
ing of 1a–e occurs by a selective Cα–O bond cleavage fol-
lowed by an alkyl group migration from C-β to C-α. This
kind of rearrangement is similar to that of α-aryl epoxides,
which is known to proceed under either photosensitiza-
tion[4d] or Lewis acid catalysis.[2b,2c,6] The photoreaction of
1a–e gave the rearrangement products (i.e., 2a–e) in excel-
lent yields, but for 1f, none of the expected product was
isolated because of the photoreaction of the 5-methylox-
indole unit in 1f with the solvent acetone. No reaction was
detected with 1g–h, even after prolonged irradiation. It
seems that the migration was very difficult for a hydrogen
atom or a phenyl group (probably due to steric hindrance)
after the Cα–O bond cleavage of the epoxide ring.
Next, we turned our attention to the synthesis of two
spiro[cycloalkane-1,3Ј-indol]-2,2Ј-diones by this benzo-
pnenone-sensitized rearrangement of bispiro epoxides 1i–j.
Under the same conditions, the photoreactions of 1i–j gave
spiro[cycloalkane-1,3Ј-indol]-2,2Ј-diones 2f–g in excellent
yields (Table 2).
In order to compare the regioselectivities of the spiroox-
indole epoxide rearrangements under different reaction
conditions, the reaction of 1a was also carried out using
Lewis acids as catalysts. After testing different catalysts,
such as BF3·Et2O, SnCl4, TiCl4, ZnCl2, and TMSOTf, the
best result was obtained in a reaction catalyzed by SnCl4.
In this case, only one product, quinoline-2,3-dione 3a,
which was different from 2a produced under photosensiti-
Results and Discussion
First, spirooxindole epoxide 1a was used as a model sub-
strate to explore the photosensitized rearrangement. After
the simple optimization of the reaction conditions in terms
of the sensitizers (acetone, benzophenone, chloranil, 9,10-
dicyanoanthracene, 2,4,6-triphenylpyrylium tetrafluorobor-
ate), and solvents (acetonitrile, dichloromethane, acetone),
the optimum yield of product 2a was obtained using benzo-
phenone as the photosensitizer in acetone. By irradiation of
a deaerated acetone solution of epoxide 1a and a catalytic
amount of benzophenone (5 mol-%) at λ Ն 350 nm at room
temperature for 5 h, 3-acetyl-3-methyl-2-indolone (2a) was
obtained in 93% yield (98% conversion). It could be specu-
lated that both benzophenone and acetone are effective for
the sensitization of the rearrangement of 1a, because 2a was
also formed in 87% yield (82% conversion) in acetone
alone after irradiation for 48 h, but the addition of benzo-
phenone greatly promoted the photoreaction of 1a.
(Scheme 2).
Scheme 2. Benzophenone-sensitized rearrangement of 1a.
The reaction of other differently substituted spirooxin- zation conditions, was formed in excellent yield (96%) in
dole epoxides 1b–h was examined under these conditions, chloroform at 35 °C (Scheme 3).
Eur. J. Org. Chem. 2012, 6606–6611
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L. Wang, Y. Su, X. Xu, W. Zhang
FULL PAPER
Table 2. Synthesis of spiro[cycloalkane-1,3Ј-indol]-2,2Ј-diones by
benzophenone-sensitized rearrangement of 1i–j.
Table 3. SnCl4-catalyzed rearrangement of spiro[indoline-3,2Ј-oxi-
ran]-2-one 1a–h.
Entry Epoxide
R1 R2 R3 R4
t
[h]
Conv.[a] Product Yield[b]
Entry Epoxide
Time
[h]
Conv.[a]
[%]
Product
Yield[b]
[%]
[%]
[%]
n
1
2
3
5
6
4
8
9
1a
1b
1c
1d
1e
1f
H
H
H
Br
CH3 CH3 CH3
CH3 CH3
Ph CH3 CH3
CH3 CH3 CH3
3
3
3
5
20
3
100
100
100
100
ca. 0
100
100
100
3a
3b
3c
3d
–
3e
4
5
93
91
95
88
–
95
86
75
1
2
1i
1j
1
2
5
5
ca. 100
ca. 100
2f
90
93
H
2g
[a] Conversion was calculated on the basis of substrates 1i–j. [b]
Yield of isolated products was based on consumed substrates 1i–j.
NO2 CH3 CH3 CH3
CH3 CH3 CH3 CH3
H
H
1g
1h
CH3
CH3
H
H
CO2Et
Ph
3
3
[a] Conversion was calculated on the basis of substrate 1a–h.
[b] Yield of isolated products was based on consumed substrates
1a–d and 1f–h.
Scheme 3. SnCl4-catalyzed rearrangement of 1a.
Other spirooxindole epoxides 1b–h were also examined
under the optimized conditions (Table 3). It can be seen
from the results in Table 3 that all the spirooxindole epox-
ides gave the rearrangement products (i.e., 3a–e) in excellent
yields, except for 1e and 1g–h. For epoxides 1a–d,f, doubly
methyl-substituted at C-β, the rearrangement products were
derived from selective Cβ–O bond cleavage and subsequent
aryl group migration from C-α to C-β. This kind of re-
arrangement has not been reported before for α,β-epoxy
ketones or α,β-epoxy lactams, because the Lewis-acid-cata-
lyzed rearrangement of α,β-epoxy ketones[6] and α,β-epoxy
lactams[13a] generally gave the 1,3-dicarbonyl compounds
by Cβ–O bond cleavage and subsequent acyl group shift.
Substituent effects are also apparent from the results in
Table 3. Electron-withdrawing groups, such as bromide or
nitro groups retarded the rearrangement. Indeed, with a ni-
tro group, no reaction could be detected, even after pro-
longed stirring. On the other hand, different products were
obtained from the reactions of 1g and 1h, as shown in
Schemes 4 and 5.
Scheme 4. SnCl4-catalyzed fragmentation of 1g.
Scheme 5. SnCl4-catalyzed ring-opening of 1h.
ones 3f and 3g were obtained in excellent yields after stir-
ring the solutions of 1i or 1j and SnCl4 in chloroform for
1
5 h. The structures of all products were identified by H
and 13C NMR spectroscopy, MS, and HRMS, and the
structure of 3g was further confirmed by X-ray crystal-
lography (Figure 1).
Obviously, both products 4 and 5 are derived from the
SnCl4-catalyzed Cα–O bond cleavage of 1g and 1h, which is
different from the Cβ–O bond cleavage that occurred with
1a–d and 1f under the same condition. A subsequent shift
of the phenyl group from C-β to C-α and decarbonylation
gave product 4. For 1h, trapping of the carbocation with a
chloride ion before the migration of a hydrogen atom could
take place led to product 5. This kind of ring-opening was
also observed in the reaction of ethyl 2,3-epoxy-2,3-di-
phenylpropionate catalyzed by SnCl4.[18]
Table 4. Synthesis of spiro[cycloalkane-1,4Ј-quinoline]-2Ј,3Ј-diones
by the SnCl4-catalyzed rearrangement of epoxides 1i and1j.
Entry Epoxide
t
[h]
Conversion
[%]
Product
Yield
[%]
Next, another two spiro[cycloalkane-1,4Ј-quinolin]-2Ј,3Ј-
diones 3f and 3g were synthesized by the SnCl4-catalyzed
rearrangement of spirooxindole epoxides 1i and 1j
(Table 4). The two spiro[cycloalkane-1,4Ј-quinolin]-2Ј,3Ј-di-
n
1
2
1i
1j
1
2
5
5
100
100
3f
3g
93
91
6608
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The Rearrangement of Spirooxindole Epoxides
product 2a (93%). Further purification was performed by
recrystallization from ethanol.
General Procedure for SnCl4-Catalyzed Reactions: SnCl4 (52 mg,
0.2 mmol) was added slowly to a solution of spiro[indoline-3,2Ј-
oxiran]-2-one (1a, 1.0 mmol) in anhydrous chloroform (25 mL),
whilst stirring. The solution was heated to 35 °C and stirred for 3 h
until the reaction was complete. The reaction was then quenched
by the addition of saturated aqueous NaHCO3 and crushed ice.
The aqueous phase was extracted with chloroform (30ϫ 2 mL).
The combined organic extracts were washed with water, dried with
anhydrous Na2SO4, and concentrated under reduced pressure. The
crude product was purified by flash column chromatography on
silica gel, eluting with hexane and acetone 14:1 (v/v), to give prod-
uct 3a (93%), which was further purified by recrystallization from
ethanol.
3-Acetyl-3-methylindolin-2-one (2a): Yellow solid; m.p. 95–97 °C.
1H NMR (400 MHz, CDCl3): δ = 9.77 (m, 1 H), 7.30 (t, J = 8.0 Hz,
1 H), 7.15 (d, J = 7.6 Hz, 1 H), 7.07 (dd, J = 14.4, 7.6 Hz, 2 H),
2.05 (s, 3 H), 1.62 (s, 3 H) ppm. 13C NMR (400 MHz, CDCl3): δ
= 200.8, 178.8, 141.1, 130.1, 129.2, 123.6, 123.2, 110.6, 62.7, 25.9,
18.7 ppm. EI-MS: m/z (%) = 189 (4), 148 (12), 147 (100), 146 (64),
128 (31), 117 (8), 91 (7), 43 (12). HRMS (ESI): calcd. for
C11H12NO2 [M + H]+ 190.0797; found 190.0795.
3-Acetyl-1,3-dimethylindolin-2-one (2b): Colorless grease. 1H NMR
(400 MHz, CDCl3): δ = 7.36 (td, J = 8.0, 0.8 Hz, 1 H), 7.15 (d, J
= 6.8 Hz, 1 H), 7.09 (t, J = 7.6 Hz, 1 H), 6.94 (d, J = 7.6 Hz, 1 H),
3.31 (s, 3 H), 1.96 (s, 3 H), 1.57 (s, 3 H) ppm. 13C NMR (400 MHz,
CDCl3): δ = 200.8, 175.7, 143.6, 129.3, 129.0, 123.4, 123.1, 108.5,
61.9, 26.5, 25.7, 18.8 ppm. EI-MS: m/z (%) = 203 (3), 161 (61), 160
(100), 132 (11), 117 (12), 43 (14). HRMS (ESI): calcd. for
C12H14NO2 [M + H]+ 204.0953; found 204.0950.
Figure 1. X-ray structure of 3g.
Conclusions
The rearrangement of spirooxindole epoxides was found
to proceed either under photosensitization conditions or
under Lewis acid catalysis. However, two kinds of products
were produced. 3-Acyloxindoles, such as spiro[cycloalkane-
1,3Ј-indol]-2,2Ј-diones, were obtained as the sole products
in a benzophenone-sensitized rearrangement by a selective
Cα–O bond cleavage and subsequent migration of an alkyl
group. 2,3-Quinolindiones, such as spiro[cycloalkane-1,4Ј-
quinolin]-2Ј,3Ј-diones, were produced in excellent yields in
a SnCl4-catalyzed rearrangement by selective Cβ–O bond
cleavage and subsequent migration of an aryl group.
3-Acetyl-1-phenylindolin-2-one (2c): Yellow solid; m.p. 101–103 °C.
1H NMR (400 MHz, CDCl3): δ = 7.56 (t, J = 7.6 Hz, 2 H), 7.46–
7.43 (m, 3 H), 7.28 (td, J = 7.6, 0.8 Hz, 1 H), 7.22 (d, J = 6.8 Hz,
1 H), 7.12 (t, J = 7.6 Hz, 1 H), 6.90 (d, J = 7.6 Hz, 1 H), 2.10 (s,
3 H), 1.70 (s, 3 H) ppm. 13C NMR (400 MHz, CDCl3): δ = 200.5,
175.2, 143.6, 134.0, 129.7 (2 C), 129.6, 129.0, 128.4, 126.3 (2 C),
126.2, 123.8, 123.6, 109.9, 62.0, 25.9, 19.1 ppm. EI-MS: m/z (%) =
265 (7), 224 (17), 223 (100), 222 (53), 194 (12), 117 (5), 77 (6), 43
(7). HRMS (ESI): calcd. for C17H16NO2 [M + H]+ 266.1110; found
266.1107.
Experimental Section
General Methods: All reagents were purchased from commercial
suppliers and were used without further purification. Flash
chromatography was carried out with silica gel (200–300 mesh).
Analytical TLC was performed with silica gel GF254 plates, and
3-Acetyl-5-bromo-1,3-dimethylindolin-2-one (2d): Pale yellow solid;
1
m.p. 109–111 °C. H NMR (400 MHz, CDCl3): δ = 7.48 (dd, J =
8.0, 2.0 Hz, 1 H), 7.29 (d, J = 1.6 Hz, 1 H), 6.81 (d, J = 8.4 Hz, 1
H), 3.29 (s, 3 H), 2.02 (s, 3 H), 1.58 (s, 3 H) ppm. 13C NMR
(400 MHz, CDCl3): δ = 200.2, 175.2, 142.6, 131.9, 131.2, 126.8,
115.7, 109.9, 61.8, 26.7, 26.0, 19.2 ppm. EI-MS: m/z (%) = 281 (11),
242 (10), 241 (95), 240 (56), 239 (100), 238 (48), 160 (15), 159 (22),
131 (19), 130 (23), 117 (13), 116 (9), 43 (30). HRMS (ESI): calcd.
for C12H12BrNO2 + H+: 282.0058; found 282.0061.
3-Acetyl-1,3-dimethyl-5-nitroindolin-2-one (2e): Yellow grease. 1H
NMR (400 MHz, CDCl3): δ = 8.33 (dd, J = 8.4, 2.0 Hz, 1 H), 8.10
(d, J = 2.0 Hz, 1 H), 7.01 (d, J = 8.8 Hz, 1 H), 3.36 (s, 3 H), 2.12
(s, 3 H), 1.67 (s, 3 H) ppm. 13C NMR (400 MHz, CDCl3): δ =
199.5, 175.7, 148.9, 143.8, 130.0, 126.2, 119.9, 108.1, 61.6, 27.2,
26.6, 19.8 ppm. EI-MS m/z (%): = 248 (10), 207 (11), 206 (100),
189 (10), 160 (23), 159 (17), 130 (13), 117 (20), 77 (6), 43 (18).
HRMS (ESI): calcd. for C12H13N2O4 [M + H]+ 249.0804; found
249.0806.
the products were visualized by UV detection. H and 13C NMR
1
(300 or 400 MHz and 75 or 100 MHz, respectively) spectra were
recorded in CDCl3. Chemical shifts (δ) are reported in ppm using
TMS as internal standard, and spin–spin coupling constants (J)
are given in Hz. High-resolution mass spectra (HRMS) were mea-
sured with a Bruker Daltonics APEX-47e spectrometer using the
ESI technique. Compounds 1a–j were prepared according to the
reported methods.[19]
General Procedure for the Photochemical Reactions: Spiro[indoline-
3,2Ј-oxiran]-2-one (1a, 1.0 mmol) and benzophenone (10 mg) were
dissolved in anhydrous acetone (50 mL). The solution was deaer-
ated by bubbling Ar through it for 30 min, and then irradiated at
λ Ն 350 nm with a medium-pressure mercury lamp (500 W) at am-
bient temperature until complete conversion of the starting mate-
rial was observed. Progress of the reaction was monitored by TLC
at regular intervals. The solvent was removed under reduced pres-
sure, and then the residue was separated by flash chromatography
on silica gel, eluting with hexane and acetone 16:1 (v/v), to give
1Ј-Methylspiro[cyclohexane-1,3Ј-indolin]-2,2Ј-dione (2f): Yellow so-
1
lid; m.p. 92–94 °C. H NMR (400 MHz, CDCl3): δ = 7.30 (t, J =
Eur. J. Org. Chem. 2012, 6606–6611
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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L. Wang, Y. Su, X. Xu, W. Zhang
FULL PAPER
7.2 Hz, 2 H), 7.09 (t, J = 7.6 Hz, 1 H), 6.84 (d, J = 8.0 Hz, 1 H),
1Ј-Methylspiro[cyclopentane-1,4Ј-quinolin]-2Ј,3Ј-dione (3f): Gray so-
lid; m.p. 95–98 °C. H NMR (400 MHz, CDCl3): δ = 7.31 (t, J =
1
3.19 (s, 3 H), 3.09–3.01 (m, 1 H), 2.62–2.56 (m, 1 H), 2.46–2.36 (m,
1 H), 2.27–1.83 (m, 5 H) ppm. 13C NMR (400 MHz, CDCl3): δ = 7.6 Hz, 2 H), 7.10 (t, J = 7.6 Hz, 1 H), 6.84 (d, J = 7.2 Hz, 1 H),
204.9, 174.1, 143.1, 129.3, 128.5, 124.4, 122.5, 108.2, 63.5, 39.6,
37.1, 26.7, 26.3, 20.2 ppm. EI-MS: m/z (%) = 229 (37), 201 (18),
200 (18), 174 (12), 173 (100), 160 (25), 158 (11), 130 (17), 117 (11),
3.20 (s, 3 H), 3.09–1.84 (m, 8 H) ppm. 13C NMR (400 MHz,
CDCl3): δ = 205.0, 174.1, 143.1, 129.3, 128.5, 124.4, 122.5, 108.3,
63.5, 39.6, 37.1, 26.8, 26.3, 20.2 ppm. EI-MS: m/z (%) = 229 (37),
77(8). HRMS (ESI): calcd. for C14H16NO2 [M + H]+ 230.1110; 201 (19), 200 (18), 173 (100), 160 (25), 130 (16), 117 (8), 77 (7).
found 230.1107.
HRMS (ESI): calcd. for C14H16NO2 [M + H]+ 230.1110; found
230.1111.
1Ј-Methylspiro[cycloheptane-1,3Ј-indolin]-2,2Ј-dione (2g): Yellow so-
1
1Ј-Methylspiro[cyclohexane-1,4Ј(1ЈH)-quinolin]-2Ј,3Ј-dione
(3g):
lid; m.p. 104–107 °C. H NMR (400 MHz, CDCl3): δ = 7.31–7.25
1
Yellow solid; m.p. 102–104 °C. H NMR (400 MHz, CDCl3): δ =
7.35 (t, J = 8.4 Hz, 2 H), 7.16 (t, J = 7.6 Hz, 1 H), 7.07 (d, J =
8.0 Hz, 1 H), 3.47 (s, 3 H), 3.30 (d, J = 13.2 Hz, 2 H), 1.82–1.63
(m, 7 H), 1.32–1.23 (m, 1 H) ppm. 13C NMR (400 MHz, CDCl3):
δ = 197.7, 158.8, 137.3, 130.8, 128.4, 125.0, 124.6, 115.8, 52.1, 32.0
(2 C), 29.6, 25.5, 22.8 (2 C) ppm. EI-MS: m/z (%) = 243 (30), 215
(14), 189 (8), 161 (12), 160 (100), 159 (17), 147 (16), 130 (12), 77
(7). HRMS (ESI): calcd. for C15H18NO2 [M + H]+ 244.1266; found
244.1269.
(m, 2 H), 7.07 (t, J = 7.6 Hz, 1 H), 6.84 (d, J = 7.6 Hz, 1 H), 3.19
(s, 3 H), 3.08–3.01 (m, 1 H), 2.75–2.71 (m, 1 H), 2.35–1.78 (m, 8
H) ppm. 13C NMR (400 MHz, CDCl3): δ = 207.4, 175.1, 143.3,
130.6, 128.5, 123.4, 122.6, 108.4, 7.37, 42.2, 34.7, 30.7, 26.6, 26.3,
25.2 ppm. EI-MS: m/z (%) = 243 (49), 215 (28), 187 (15), 186 (100),
160 (92), 159 (33), 147 (26), 130 (25), 117 (10), 77 (8). HRMS (ESI):
calcd. for C15H18NO2 [M + H]+ 244.1266; found 244.1264.
4,4-Dimethylquinoline-2,3-dione (3a): Yellow grease. 1H NMR
(400 MHz, CDCl3): δ = 10.46 (s, 1 H), 7.33 (dd, J = 8, 1.2 Hz, 1
H), 7.30–7.26 (m, 1 H), 7.15 (td, J = 7.6, 1.2 Hz, 1 H), 7.09 (dd, J
= 8, 1.2 Hz, 1 H), 1.57 (s, 6 H) ppm; 13C NMR (400 MHz, CDCl3)
δ = 196.3, 156.7, 132.8, 130.7, 128.5, 125.9, 124.8, 117.2, 49.1, 24.8
(2C) ppm. EI-MS: m/z (%) = 190 (8), 189 (64), 161 (29), 146 (100),
133 (12), 132 (25), 128 (36), 118 (17), 117 (14), 91 (15), 77 (8), 65
(8). HRMS (ESI): calcd. for C11H12NO2 [M + H]+ 190.0797; found
190.0795.
Crystal Data for 3g: Recrystallization from ethanol, C15H17NO2,
Mr = 243.30, triclinic, a = 9.071(13) Å, b = 11.312(16) Å, c =
12.524(18) Å, β = 91.457(14)°, V = 1268(3) Å3, yellow block, Dc =
1.275 gcm–3, T = 296(2) K, space group: P21/c, Z = 4, μ (Mo-
Kα) = 0.71073 mm–1, 2θmax = 51.00, 4630 reflection collected, 2778
unique (Rinit = 0.0657) which was used in all calculations. Final
wR(F2) = 0.1636 (all data). CCDC file No. 894241.
1-Methyl-3-phenylindolin-2-one (4): Pale yellow solid; m.p. 113–115
°C. 1H NMR (400 MHz, CDCl3): δ = 7.35–7.25 (m, 4 H), 7.21–
7.15 (m, 3 H), 7.06 (t, J = 7.6 Hz, 1 H), 6.90 (d, J = 7.6 Hz, 1 H),
4.60 (s, 1 H), 3.25 (s, 3 H) ppm. 13C NMR (400 MHz, CDCl3): δ
= 175.9, 144.4, 136.6, 128.8 (2 C), 128.7, 128.4 (2 C), 127.6, 125.0,
122.7, 108.1, 52.0, 26.4 ppm. EI-MS: m/z (%) = 224 (16), 223 (100),
195 (14), 194 (89), 165 (12), 146 (12), 118 (10), 97 (7). HRMS (ESI):
calcd. for C15H14NO [M + H]+ 224.1004; found 224.1002.
1,4,4-Trimethylquinoline-2,3-dione (3b): Pale yellow solid; m.p. 96–
99 °C. H NMR (400 MHz, CDCl3): δ = 7.38–7.35 (m, 2 H), 7.18
1
(t, J = 7.6 Hz, 1 H), 7.10 (d, J = 8 Hz, 1 H), 3.53 (s, 3 H), 1.54 (s,
6 H) ppm. 13C NMR (400 MHz, CDCl3): δ = 195.4, 156.9, 136.5,
130.6, 128.5, 125.5, 124.6, 115.6, 48.2, 30.1, 23.8 (2 C) ppm. EI-
MS: m/z (%) = 203 (44), 175 (27), 161 (10), 160 (100), 132 (28),
130 (9), 117 (18), 115 (6), 77 (8), 44(7). HRMS (ESI): calcd. for
C12H14NO2 [M + H]+ 204.0907; found 204.0909.
Ethyl 2-Hydroxy-2-(3-chloro-1-methyl-2-oxoindolin-3-yl)acetate (5):
Pale yellow solid; m.p. 101–104 °C. H NMR (300 MHz, CDCl3):
4,4-Dimethyl-1-phenylquinoline-2,3-dione (3c): Pale yellow solid;
m.p. 202–204 °C. 1H NMR (400 MHz, CDCl3): δ = 7.58 (t, J =
7.2 Hz, 2 H), 7.50 (t, J = 7.2 Hz, 1 H), 7.41–7.38 (m, 1 H), 7.31 (d,
J = 8.4 Hz, 2 H), 7.16–7.12 (m, 2 H), 6.48–6.46 (m, 1 H), 1.66 (s,
6 H) ppm. 13C NMR (400 MHz, CDCl3): δ = 195.9, 156.6, 137.9,
136.7, 130.4, 130.2 (2 C), 129.0, 128.3 (2 C), 128.2, 125.5, 124.8,
118.2, 48.6, 23.7 (2 C) ppm. EI-MS: m/z (%) = 265 (50), 238 (28),
237 (100), 223 (33), 222 (87), 209 (22), 194 (76), 181 (31), 180 (27),
149 (39), 132 (30), 118 (28), 117 (20), 77 (22), 57 (22), 43 (30).
HRMS (ESI): calcd. for C17H16NO2 [M + H]+ 266.1110; found
266.1111.
1
δ = 7.39 (td, J = 7.5, 1.2 Hz, 1 H), 7.31 (d, J = 7.5 Hz, 1 H), 7.11
(t, J = 7.8 Hz, 1 H), 6.87 (d, J = 7.8 Hz, 1 H), 4.74 (d, J = 9.9 Hz,
1 H), 4.24–4.15 (m, 2 H), 3.72 (d, J = 9.3 Hz, 1 H), 3.25 (s, 3 H),
1.19 (t, J = 7.2 Hz, 3 H) ppm. 13C NMR (300 MHz, CDCl3): δ =
172.4, 170.2, 143.7, 131.0, 125.2, 125.1, 123.3, 108.8, 74.7, 62.5,
62.2, 26.7, 13.9 ppm. EI-MS: m/z (%) = 283 (10), 183 (33), 181
(100), 180 (50), 146 (43), 118 (15), 117 (10), 91 (12), 44 (7). HRMS
(ESI): calcd. for C13H15ClNO4 [M + H]+ 284.0618; found 284.0620.
Supporting Information (see footnote on the first page of this arti-
1
cle): Analytical data of all substrates and copies of the H and 13
C
6-Bromo-1,4,4-trimethylquinoline-2,3-dione (3d): Pale yellow solid;
m.p. 150–152 °C. 1H NMR (400 MHz, CDCl3): δ = 7.48 (d, J =
2.4 Hz, 1 H), 7.46 (s, 1 H), 6.97 (d, J = 8.4 Hz, 1 H), 3.50 (s, 3 H),
1.53 (s, 6 H) ppm. 13C NMR (400 MHz, CDCl3): δ = 194.3, 156.5,
135.8, 132.8, 131.5, 128.7, 117.6, 117.2, 48.4, 30.3, 23.8 (2 C) ppm.
EI-MS: m/z (%) = 283(47), 281 (46), 255 (55), 253 (58), 240 (100),
159 (57), 131 (87), 130 (57), 115 (14), 57 (13), 44 (15). HRMS (ESI):
calcd. for C12H13BrNO2 [M + H]+ 282.0058; found 282.0061.
NMR spectra for all products.
Acknowledgments
We are grateful to the National Nature Science Foundation of
China (NSFC) (grant numbers 20872056 and J1103307) for finan-
cial support.
1,4,4,6-Tetramethylquinoline-2,3-dione (3e): Yellow solid; m.p. 95–
97 °C. H NMR (400 MHz, CDCl3): δ = 7.15 (d, J = 4.8 Hz, 2 H),
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Received: July 30, 2012
Published Online: October 5, 2012
Eur. J. Org. Chem. 2012, 6606–6611
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
6611