Mn(III)-based oxidative cyclization of N-aryl-3-oxobutanamides. facile synthesis and transformation of substituted oxindoles

Article abstract of DOI:10.3987/COM-14-S(K)57

The oxidation of 3-oxo-N-phenylbutanamides 1 with manganese(III) acetate in ethanol afforded dimeric 3,3'-biindoline-2,2'-dione derivatives 3-5. A similar reaction of N,2-disubstituted N-aryl-3-oxobutanamides 6 in acetic acid produced 3-acetylindolin-2-ones 7 bearing various substituents in good to excellent yields. The acetylindolinones 7 were easily deacetylated by treatment using neutral alumina in diethyl ether. Both the acetylindolinones 7 and deacetylated indolinones 8 were transformed by reduction into the substituted 1H-indoles.

Full text of DOI:10.3987/COM-14-S(K)57

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HETEROCYCLES, Vol. 90, No. 1, 2015
HETEROCYCLES, Vol. 90, No. 1, 2015, pp. 540 - 562. © 2015 The Japan Institute of Heterocyclic Chemistry
Received, 30th June, 2014, Accepted, 16th July, 2014, Published online, 22nd July, 2014
DOI: 10.3987/COM-14-S(K)57
Mn(III)-BASED OXIDATIVE CYCLIZATION OF
N-ARYL-3-OXOBUTANAMIDES. FACILE SYNTHESIS AND
TRANSFORMATION OF SUBSTITUTED OXINDOLES†
Nobutaka Kikue, Tetsuya Takahashi, and Hiroshi Nishino*
Department of Chemistry, Graduate School of Science and Technology,
Kumamoto University, Kurokami 2-39-1, Chûou-Ku, Kumamoto 860-8555,
Japan
Fax: +81-96-342-3374; E-mail: nishino@sci.kumamoto-u.ac.jp
†Dedicated to Prof. Dr. Isao Kuwajima, Professor emeritus of Tokyo Institute of
Technology, on his 77th birthday
Abstract – The oxidation of 3-oxo-N-phenylbutanamides 1 with manganese(III)
acetate in ethanol afforded dimeric 3,3'-biindoline-2,2'-dione derivatives 3–5. A
similar reaction of N,2-disubstituted N-aryl-3-oxobutanamides 6 in acetic acid
produced 3-acetylindolin-2-ones 7 bearing various substituents in good to
excellent yields. The acetylindolinones 7 were easily deacetylated by treatment
using neutral alumina in diethyl ether. Both the acetylindolinones 7 and
deacetylated indolinones 8 were transformed by reduction into the substituted
1H-indoles.
INTRODUCTION
Many of the chemistries for indoles and their derivatives have been investigated and reported.1 However,
the synthesis and reaction of these heterocycles are still attractive from the view point of the synthetic
method,2 total synthesis of natural products,3 biological and pharmacological activities,1b,4 and material
science.5 Recently, we reported the Mn(III)-mediated direct substitution of methoxynaphthalenes with
N-aryl-3-oxobutanamides, giving the 3-oxobutanamide-substituted naphthalene I in addition to a small
amount of demethoxylated naphthofuran II and benzoindolinone III (Scheme 1, eq. 1).6 Although the
yield of the heterocyclic compounds II and III was poor, the carbon-carbon bond formation efficiently
occurred during the reaction.7 We also reported the facile synthesis of 3,4-dihydro-2(1H)-quinolinones,

HETEROCYCLES, Vol. 90, No. 1, 2015
541
such as IV, by the Mn(III)-based oxidative cyclization of 2-(2-arylamino-2-oxoethyl)malonates (Scheme
1, eq. 2).8 In the reaction, the formal 6-endo-trig-type cyclization (cyclization at the ortho position) was
superior to the formal 5-exo-trig-type (ipso-cyclization) except for the case of the malonates bearing an
electron-rich aryl group, producing spiro compounds, such as V. It is also known that 2’-hydroxychalcone
undergoes the 5-exo-trig cyclization to afford the aurone.9 In either event, it shows that the construction
of heterocycles using the Mn(III)-based carbon-carbon bond formation is convenient.10 In order to favor
the 5-exo-trig cyclization using the reaction, N-aryl-3-oxobutanamides 1 should be the most appropriate
candidate for the synthesis of nitrogen heterocycles, such as oxindoles (indolin-2-ones). It prompted us to
investigate this reaction. In this paper, we describe the facile synthesis of substituted indolin-2-ones using
the Mn(III)-based oxidation of N-aryl-3-oxobutanamides and transformation into the corresponding
1H-indoles.
Scheme 1. Carbon-Carbon Bond Formation Using Mn(III)-Based Oxidation
RESULTS AND DISCUSSION
We first prepared the 3-oxo-N-phenylbutanamides 1a-c from the reaction of the corresponding anilines
with diketene, and examined the reaction with manganese(III) acetate, Mn(OAc)3 (Scheme 2). The
reaction was carried out in acetic acid at reflux temperature similar to the oxidation of malonates as
shown in Scheme 1, eq. 2.8 Although the oxidation finished within 2-3 minutes along with some recovery
of the unchanged 3-oxobutanamides 1, the reaction was very complicated and none of the desired
indolinones were detected. The formation of the Mn(III)-enolate complex with 1 would possibly be fast

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HETEROCYCLES, Vol. 90, No. 1, 2015
and successive electron transfer should easily occur,10a,11 so that the oxidation would cause a-cleavage of
the amide bond to produce polymeric compounds.12 In order to recognize the oxidative radical reaction,
the reaction was conducted in the presence of 1,1-diphenylethene as a radical trapping reagent, and
2-methyl-N,5,5-triphenyl-4,5-dihydrofuran-3-carboxamide VI could be obtained (Scheme 2 and also see
the Experimental Section). Since the radical trapping product VI was confirmed, we investigated the
reaction of 1b (R = Me) in neutral solvent, such as ethanol, to decrease the reaction rate.10a,13 Although
the reaction did not proceed at room temperature for 2 days, the oxidation occurred at elevated
temperature and the dimeric indolin-2-ones 3, 4, and 5 were obtained (Scheme 2). Unfortunately,
dimerization of the indolinone intermediate 2b could not be controlled under the various reaction
conditions.
Scheme 2. Reaction of 3-Oxo-N-phenylbutanamides 1a–c with Mn(OAc)3
The results suggested that the formation of the Mn(III)-enolate complex with both 1b and 2b was still fast
in ethanol and the indolinone 2b was sufficiently reactive to dimerize under the stated conditions.
However, we were able to isolate the cyclization products 3–5 even in low yields using the Mn(III)-based
oxidation. In order to prevent the dimerization, we next explored the reaction using
3-oxo-N-phenylbutanamides
N,2-dimethyl-N-phenyl-3-oxobutanamide (6a), prepared by the methylation of 1b, and the reaction was
carried out under the above conditions in ethanol, producing the desired
bearing
a
substituent
at
the
2-position.
We
selected
3-acetyl-1,3-dimethylindolin-2-one (7a) (Scheme 3). A stoichiometric amount of the oxidant was
consumed within 12 minutes and the product 7a was obtained in 71% yield (Table 1, Entry 1).
Surprisingly, separation using a neutral alumina column after the reaction led to the deacetylation product
8a (Entries 2, 3) (vide infra). The reaction in propanol did not proceed (Entry 4). However, when the

HETEROCYCLES, Vol. 90, No. 1, 2015
543
reaction was conducted in glacial acetic acid, the oxidant was consumed within 3 minutes and the
acetylindolinone 7a was quantitatively produced (Entry 5). The structure of 7a was easily characterized
by disappearance of the quartet of methine proton and the collapsing of a doublet of the methyl group at
the C-2 position of 6a to a singlet of the corresponding methyl group of 7a in the 1H NMR spectrum (see
Experimental section).
Scheme 3. Oxidation of N,2-Dialkyl-N-aryl-3-oxobutanamides 6a–s with Mn(OAc)3
With the efficient oxidative cyclization in hand, we applied the reaction to various substituted
3-oxobutanamides 6b–s in order to examine the substituent effect (Scheme 3 and Table 1, Entries 6-35).
Introduction of a deactivating group toward an electrophile, such as a halogen atom in R1 on the aromatic
ring, led to prolonging the reaction time (Table 1, Entries 6, 8, 9). On the other hand, an activating group
in R1 tended to be similar or shortened the reaction time (Entries 10–12, 15, 16). In both cases,
indolinones 7b–i were produced in high to quantitative yields. An N-alkyl or N-phenyl- substituent in R2
did not influence the cyclization, but all of 6j–m gave the corresponding indolinones 7j–m in high yields
(Entries 17–20). When butanamide 6n bearing an ethyl group in R3 at the 2-position of the
3-oxobutanamide underwent the reaction under similar conditions, indolinone 7n was obtained in a
moderate yield together with the unchanged 6n (Entry 21). Use of an excess amount of the oxidant led to
the production of 7n in an almost quantitative yield (Entry 23). However, it took a longer reaction time to
consume the oxidant. This tendency was also observed in the reaction of 6o (R3 = propyl), 6p (R3 =
i-propyl), and 6q (R3 = butyl) (Entries 24–30). In the case of butylbutanamide 6q, the use of a large
amount of the oxidant resulted in deacetylation followed by overoxidation to afford
3-acetoxy-3-butyl-1-methylindolin-2-one (9) (Entries 29, 30). N-Naphthylbutanamides 6r and 6s also
produced the corresponding benzoindolinones 7r and 7s in excellent yields (Entries 33, 35).
Most of the reactions proceeded in acetic acid for 3–6 minutes using a stoichiometric amount of
Mn(OAc)3 to give the corresponding indolinones 7. The plausible mechanism for the formation of 7 is
outlined in Scheme 4. The rate-determining step would be the stage (6 ! A) for the formation of the
Mn(III)-enolate complex A.10a,11 Therefore, the bulky alkyl group of substituent R3 made the reaction rate

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HETEROCYCLES, Vol. 90, No. 1, 2015
slower and a steric hindrance derived from the bulkiness inhibited the cyclization affording the
intermediate radical B. In order to accelerate the reaction, an excess amount of the oxidant would be
necessary (Entries 23, 25, 27, 29).
Table 1. Mn(III)-Based Oxidation of N,2-Dialkyl-N-aryl-3-oxobutanamides 6a-sa
ꢀ
ꢀ
ꢀ
b
Entry
1
ꢀ
6a
6a
6a
6a
6a
6b
6c
6c
6d
6e
6f
R1
R2
R3
6:Mn(OAc)3
Solvent
EtOH
Time/min
Product (yield/%)c
Rec. 6d
H
Me
Me
1:2
12
12
45
240
3
7a (71)
2
EtOH
8a (68)e
8a (99)e
3
MeOH
PrOH
4
100
54
5
AcOH
AcOH
EtOH
7a (quant)
7b (99)
6
4-F
4-Cl
4-Cl
2-Cl
4-Me
2-Me
4-MeO
3-MeO
3-MeO
3-MeO
2-MeO
H
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Et
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Et
1:2
1:2
1:2
1:2
1:2
1:2
1:2
1:2
1:2
1:2
1:2
1:2
1:2
1:2
1:2
1:2
1:3
1:4
1:2
1:4
1:2
1:4
1:2
1:4
1:6
1:2
1:2
1:3
1:2
1:3
6
7
30
6
8c (31)e
8
AcOH
AcOH
AcOH
AcOH
AcOH
EtOH
7c (quant)
7d (quant)
7e (quant)
7f (94)
9
6
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
3
3
6g
6h
6h
6h
6i
2
7g (89)
9
8h (53)e
8h (76)e
MeOH
AcOH
AcOH
AcOH
AcOH
AcOH
AcOH
AcOH
40
2
21
7h (83)f
7i (89)
7j (96)
7k (98)
7l (93)
7m (91)
7n (46)
7n (64)
7n (98)
7o (57)
7o (94)
7p (3)
3
6j
3
6k
6l
H
Bu
4
H
i-Pr
Ph
3
6m
6n
6n
6n
6o
6o
6p
6p
6q
6q
6q
6r
6r
6r
6s
H
2
H
Me
3
26
6
4
19
3
H
H
H
Me
Me
Me
Pr
i-Pr
Bu
AcOH
AcOH
AcOH
AcOH
AcOH
40
8
5
53
30
20
13
5
7p (4)
7q (80)
7q (81)
7q (40)
15
60
360
6
9 (10)
9 (60)
1-Naphg
Me
Me
Me
Me
EtOH
AcOH
AcOH
AcOH
AcOH
8r (63)e
7r (73)
7r (96)
7s (79)
7s (99)
23
10
8
2-Naphg
ꢀ
ꢀ
21ꢀ
6s
10
ꢀ
a The reaction of 6 (0.5 mmol) was carried out in solvent (15 mL) at reflux temperature in air.
b Molar ratio.
c The yield was based on the amount of the 3-oxobutanamide 6 used.
d Recovery.
e The separation was performed by neutral Al2O3 eluting with Et2O–hexane (7:3 v/v).
f The regioisomer ratio was 6-MeO-7h:4-MeO-7h = 1.8:1.
g The naphthyl group was represented as N-aryl group substituted by R1 of 6 in Scheme 3.

HETEROCYCLES, Vol. 90, No. 1, 2015
545
Scheme 4. Plausible Mechanism for the Formation of Indolinones 7
We unexpectedly found the deacetylation during the separation and purification of the acetylindolinones 7
through a neutral alumina column (Table 1, Entries 2, 3, 7, 13, 14, 31). We were interested in the facile
deacetylation affording indolinones 8, so that we scrutinized the reaction (Scheme 5). When
acetylindolinone 7a (R1 = H) was treated in aqueous acetic acid, or acetic acid in the presence of
Mn(OAc)2•4H2O, or in diethyl ether alone at 23 °C to reflux temperature, no reaction occurred and 7a
was recovered unchanged (Table 2, Entries 1–3). However, when neutral alumina was added to 7a in
diethyl ether and the mixture was stirred at room temperature in a flask, the deacetylation somewhat
proceeded (Entry 4). After optimizing the reaction, a quantitative yield of 8a was achieved within 1 hour
in diethyl ether (Entry 7). Methanol instead of diethyl ether as the solvent was not effective for the
deacetylation (Entry 8). Other acetylindolinones 7b and 7g also underwent the deacetylation to give
similar results (Entries 9, 10).
Scheme 5. Deacetylation of 3-Actyl-1,3-dimethylindolin-2-ones 7a, b, g

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HETEROCYCLES, Vol. 90, No. 1, 2015
Table 2. Deacetylation of 3-Actyl-1,3-dimethylindolin-2-ones 7a, b, ga
ꢀ
ꢀ
ꢀ
ꢀ
Rec. 7c
100
100
100
82
Entry
ꢀ
R1
Solvent
AcOH
AcOH
Et2O
Additive
H2O
Time/h
Temp
Product (yield/%)b
1
2
7a
7a
7a
7a
7a
7a
7a
7a
7b
7g
H
2 mL
0.25
0.25
1
rt to reflux
Mn(OAc)2
none
0.25 g
rt to reflux
3
rt to reflux
4
Et2O
Al2O3
0.5 g
0.5 g
1.5 g
7 g
1
rt
8a (18)
5
12
1
reflux
8a (51)
49
6
rt
rt
rt
rt
rt
8a (61)
39
7
1
8a (quant)
8
MeOH
Et2O
Al2O3
Al2O3
Al2O3
7 g
1
100
9
5-F
7 g
1
8b (72)
8g (96)
10
5-MeO
Et2O
7 g
1
a The reaction of 7 (0.5 mmol) was carried out in solvent (15 mL).
b The yield was based on the amount of the dimethylindolinone 7 used.
c Recovery.
Although some methods are known for the transformation into indoles,14 we finally investigated the
convenient route to substituted indoles from indolinones. With deacetylated indolinones 8 in hand, we
examined the reduction of 8.15 The reaction using LiAlH4 (LAH) was carried out in dry tetrahydrofuran
(THF) at 0 °C for 1 hour, then at room temperature for 4 hours, giving the desired indole 10a (Scheme 6).
Since the reduction was quite easy, we tried to directly reduce the acetylindolinone 7a under the same
conditions. Fortunately, the reduction efficiently proceeded and the desired indole 10a was produced in
good yield. The reduction of the other indolinones 7b, g and 8b, g also gave similar results (Scheme 6).
Scheme 6. Reduction of Indolin-2-ones 7 and 8 with LAH
CONCLUSION
We demonstrated the facile synthesis of 3-acetylindolin-2-ones 7 using a stoichiometric amount of
Mn(OAc)3 in most cases, with a short reaction time and in high to quantitative yields, and also a simple

HETEROCYCLES, Vol. 90, No. 1, 2015
547
retro-Claisen-like deacetylation of 7 by stirring with neutral alumina in diethyl ether at room temperature.
In addition, both the 3-acetylindolinones 7 and the deacetylated 8 were easily transformed by normal
LAH reduction into the corresponding indoles 10. Although some skillful methods for the synthesis of
indolinones were recently reported,16 to the best of our knowledge, the Mn(III)-based oxidative
cyclization of 3-oxobutanamides is one of the simplest and most convenient methods for the synthesis of
substituted indolinone derivatives.
EXPERIMENTAL
Measurements. Melting points were taken using a Yanagimoto micromelting point apparatus and are
uncorrected. The NMR spectra were recorded using a JNM AL300 or ECX 500 FT-NMR spectrometer at
300 or 500 MHz for 1H and at 75 or 125 MHz for 13C, with tetramethylsilane as the internal standard. The
chemical shifts are reported in ! values (ppm) and the coupling constants in Hz. The IR spectra were
measured in CHCl3 or KBr using a Shimadzu 8400 FT IR spectrometer and expressed in cm!1. The EI
MS spectra were obtained by a Shimadzu QP-5050A gas chromatograph-mass spectrometer at the
ionizing voltage of 70 eV. The high-resolution mass spectra and the elemental analyses were performed at
the Instrumental Analysis Center, Kumamoto University, Kumamoto, Japan.
Materials. Manganese(II) acetate tetrahydrate, Mn(OAc)2•4H2O, was purchased from Wako Pure
Chemical Ind., Ltd. Manganese(III) acetate dihydrate, Mn(OAc)3•2H2O, was prepared according to the
modified method described in the literature (vide infra).17,18 Aniline and the substituted anilines from
Wako Pure Chemical Ind., Ltd., naphthylamines from Kanto Chemical Co., Inc., and diketene and lithium
aluminum hydride from Tokyo Kasei Co., Ltd., were purchased and used as received. The
N-methylanilines were prepared by condensation of the corresponding anilines with paraformaldehyde in
the presence of sodium methoxide in methanol followed by reduction with sodium borohydride. The
other N-alkylanilines were purchased from Sigma-Aldrich Co., LLC. The N,2-dialkyl-3-oxobutanamides
6a-s were prepared by the reaction of neat N-alkylanilines with diketene followed by alkylation of the
alkyl bromides in the presence of sodium hydride in dry tetrahydrofuran (THF). Flash column
chromatography was performed on silica gel 60N (40-50 mm), which was purchased from Kanto
Chemical Co., Inc., and thin layer chromatography (TLC) on Wakogel B-10 (45 mm) from Wako Pure
Chemical Ind., Ltd. The activated neutral aluminum oxide (Al2O3) was purchased from Sigma-Aldrich
Co., LLC.
Modified Preparation of Manganese(III) Acetate Dihydrate.17,18 To a 2 L round-bottomed flask,
Mn(OAc)2•4H2O (66 g, 0.27 mol) and glacial AcOH (660 mL) were added and the mixture was heated at
90 °C to dissolve the components (normally for 10-30 min). The mixture must not be heated under reflux.
After cooling, acetic anhydride (96 mL) was added to the mixture with stirring. Three portions of ground

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HETEROCYCLES, Vol. 90, No. 1, 2015
potassium permanganate, KMnO4, (11 g, 0.07 mol) were then slowly added with stirring. The mixture
was heated under reflux for 1 h (Caution: the added KMnO4 must be dissolved in the reaction mixture.
Otherwise the reaction mixture could be bumpy while cooling on the bench! Very dangerous!). After
cooling, water (110 mL) was added and the mixture was kept at room temperature under dark conditions
until the dark color of the supernatant solution turned transparent normally within for 2 weeks. The
crystalline manganese(III) acetate formed was filtered, washed three times with glacial AcOH, washed
twice with dried Et2O, and dried in a desiccator under reduced pressure using KOH as a drying agent,
resulting in the bright-brown color of Mn(OAc)3•2H2O (67 g, 93% yield).
N,2-Dimethyl-3-oxo-N-phenylbutanamide (6a).16j,19 Yield 96%. Yellow liquid. IR (CHCl3): " 1724
(C=O), 1651 (CONH) cm-1. 1H NMR (300 MHz, CDCl3): ! 7.49-7.36 (3H, m, arom H), 7.27-7.19 (2H, m,
arom H), 3,41 (1H, q, J = 6.9 Hz, CH), 3.31 (3H, s, NMe), 2.02 (3H, s, Ac), 1.27 (3H, d, J = 6.9 Hz, Me)
ppm. 13C NMR (75 MHz, CDCl3): ! 204.9 (C=O), 170.6 (N-C=O), 143.5, 130.1, 128.4, 127.5 (arom C),
51.6 (CH), 37.6 (N-Me), 27.9 (Ac), 13.9 (Me) ppm. HRMS (acetone/NBA) calcd for C12H16NO2
206.1181 (M+H). Found 206.1185.
N-(4-Fluorophenyl)-N,2-dimethyl-3-oxobutanamide (6b). Yield 92%. Orange liquid. IR (CHCl3): "
1719 (C=O), 1653 (CONH) cm-1. 1H NMR (300 MHz, CDCl3): ! 7.22-7.10 (4H, m, arom H), 3.37 (1H, q,
J = 6.9 Hz, CH), 3.28 (3H, s, N-Me), 2.03 (3H, s, Ac), 1.27 (3H, d, J = 6.9 Hz, Me) ppm. 13C NMR (75
MHz, CDCl3): ! 204.9 (C=O), 170.6 (N-C=O), 163.7, 160.4, 139.5, 129.5, 129.4, 117.2, 116.9 (arom C),
51.6 (CH), 37.8 (N-Me), 27.9 (Ac), 14.0 (Me) ppm. FAB HRMS (acetone/NBA) calcd for C12H15FNO2
224.1087 (M+H). Found 224.1089.
N-(4-Chlorophenyl)-N,2-dimethyl-3-oxobutanamide (6c). Yield 91%. Yellow liquid. IR (CHCl3): "
1
1724 (C=O), 1655 (CONH) cm-1. H NMR (300 MHz, CDCl3): ! 7.44-7.41 (2H, m, arom H), 7.17-7.14
(2H, m, arom H), 3.38 (1H, q, J = 7.2 Hz, CH), 3.28 (3H, s, NMe), 2.05 (3H, s, Ac), 1.28 (3H, d, J = 7.2
13
Hz, Me) ppm. C NMR (75 MHz, CDCl3): ! 204.8 (C=O), 170.4 (N-C=O), 142.0, 134.3, 130.3, 128.9
(arom C), 51.6 (CH), 37.7 (N-Me), 27.9 (Ac), 14.0 (Me) ppm. HRMS (acetone/NBA) calcd for
C12H15ClNO2 240.0791 (M+H). Found 240.0797.
N-(2-Chlorophenyl)-N,2-dimethyl-3-oxobutanamide (6d). Rotamer ratio = 1.28:1. Yield quant.
1
Colorless liquid. IR (CHCl3): " 1716 (C=O), 1655 (CONH) cm-1. H NMR (500 MHz, CDCl3): !
7.58-7.53 (1H, m, arom H), 7.42-7.28 (3H, m, arom H), 3.26, 3.25 (3H, s, Me), 3.24-3.16 (1H, m, CH),
13
2.19, 2.01 (3H, s, Ac), 1.33, 1.23 (3H, d, J = 6.9 Hz, Me) ppm. C NMR (125 MHz, CDCl3): ! 205.0,
203.5 (C=O), 171.2, 170.1 (N-C=O), 140.33, 140.32, 132.9, 132.7, 130.9, 130.6, 130.0, 129.9, 129.7,
128.4 (arom C), 51.8, 51.4 (CH), 36.1, 36.0 (N-Me), 28.0, 27.6 (Ac), 13.9, 13.6 (Me) ppm. FAB HRMS
(acetone/NBA) calcd for C12H15ClNO2 240.0791 (M+H). Found 240.0802.

HETEROCYCLES, Vol. 90, No. 1, 2015
549
N-(4-Methylphenyl)-N,2-dimethyl-3-oxobutanamide (6e).16j Yield 73%. Yellow liquid. IR (CHCl3): "
1
1720 (C=O), 1651 (CONH) cm-1. H NMR (300 MHz, CDCl3): ! 7.27-7.23 (2H, m, arom H), 7.09-7.06
(2H, m, arom H), 3.41 (1H, q, J = 6.9 Hz, CH), 3.28 (3H, s, N-Me), 2.39 (3H, s, Me), 2.03 (3H, s, Ac),
13
1.25 (3H, d, J = 6.9 Hz, Me) ppm. C NMR (75 MHz, CDCl3): ! 204.9 (C=O), 170.8 (N-C=O), 140.1,
138.4, 130.7, 127.2 (arom C), 51.5 (CH), 37.7 (N-Me), 27.9 (Ac), 21.1 (Me), 13.9 (Me) ppm. FAB
HRMS (acetone/NBA) calcd for C13H18NO2 220.1338 (M+H). Found 220.1337.
N-(2-Methylphenyl)-N,2-dimethyl-3-oxobutanamide (6f).16j Rotamer ratio = 1.24:1. Yield 84%. Brown
liquid. IR (CHCl3): " 1720 (C=O), 1651 (CONH) cm-1. 1H NMR (500 MHz, CDCl3): ! 7.33-7.24 (3H, m,
arom H), 7.12-7.10 (1H, m, arom H), 3.29-3.18 (1H, m, CH), 3.23, 3,22 (3H, s, NMe), 2.28, 2.23 (3H, s,
13
Me), 2.03, 2.00 (3H, s, Ac), 1.28, 1.26 (3H, d, J = 6.9 Hz, Me) ppm. C NMR (125 MHz, CDCl3): !
205.0, 204.7 (C=O), 171.1, 170.5 (N-C=O), 141.8, 141.7, 135.9, 135.4, 131.9, 131.6, 128.8, 128.7, 128.5,
128.1, 127.6, 127.4 (arom C), 51.54, 51.52 (CH), 36.3 (N-Me), 27.9, 27.8 (Ac), 17.4, 17.3 (Me), 14.3,
14.1 (Me) ppm. Anal. Calcd for C13H17NO2: C, 71.21; H, 7.81; N, 6.39. Found: C, 71.18; H, 8.02; N,
6.27.
N-(4-Methoxylphenyl)-N,2-dimethyl-3-oxobutanamide (6g). Yield 62%. Orange liquid. IR (CHCl3): "
1
1720 (C=O), 1651 (CONH) cm-1. H NMR (300 MHz, CDCl3): ! 7.14-7.09 (2H, m, arom H), 6.96-6.91
(2H, m, arom H), 3.82 (3H, s, OMe), 3.42 (1H, q, J = 6.9 Hz, CH), 3.27 (3H, s, N-Me), 2.03 (3H, s, Ac),
13
1.26 (3H, d, J = 6.9 Hz, Me) ppm. C NMR (75 MHz, CDCl3): ! 205.0 (C=O), 171.0 (N-C=O), 159.3,
136.2, 128.6, 115.1 (arom C), 55.5 (OMe), 51.5 (CH), 37.8 (N-Me), 28.0 (Ac), 13.9 (Me) ppm. FAB
HRMS (acetone/NBA) calcd for C13H18NO3 236.1287 (M+H). Found 236.1288.
N-(3-Methoxyphenyl)-N,2-dimethyl-3-oxobutanamide (6h). Yield 86%. Yellow liquid. IR (CHCl3): "
1
1720 (C=O), 1651 (CONH) cm-1. H NMR (300 MHz, CDCl3): ! 7.38-7.33 (1H, m, arom H), 6.94-6.90
(1H, m, arom H), 6.81-6.73 (2H, m, arom H), 3.83 (3H, s, OMe), 3.46 (1H, q, J = 6.0 Hz, CH), 3.30 (3H,
s, NMe), 2.05 (3H, s, Ac), 1.27 (3H, d, J = 6.0 Hz, Me) ppm. 13C NMR (75 MHz, CDCl3): ! 204.9 (C=O),
170.6 (N-C=O), 160.7, 144.6, 130.8, 119.5, 113.7, 113.4 (arom C), 55.5 (OMe), 51.2 (CH), 37.5 (NMe),
28.0 (Ac), 14.0 (Me) ppm. HRMS (acetone/NBA) calcd for C13H18NO3 236.1287 (M+H). Found
236.1282.
N-(2-Methoxylphenyl)-N,2-dimethyl-3-oxobutanamide (6i). Rotamer ratio = 1.37:1. Yield 58%.
1
Colorless microcrystals (from EtOH), mp 66-67 °C. IR (CHCl3): " 1720 (C=O), 1651 (CONH) cm-1. H
NMR (300 MHz, CDCl3): ! 7.38-7.34 (1H, m, arom H), 7.19-7.17 (1H, m, arom H), 7.16-6.98 (2H, m,
arom H), 3.85, 3.84 (3H, s, OMe), 3.30-3.21 (1H, m, CH), 3.22, 3.21 (3H, s, N-Me), 2.12, 2.02 (3H, s,
Ac), 1.23, 1.21 (3H, d, J = 6.0 Hz, Me) ppm. 13C NMR (75 MHz, CDCl3): ! 205.1, 204.6 (C=O), 171.8,
171.2 (N-C=O), 154.9, 131.8, 129.9, 129.8, 129.5, 128.9, 121.3, 112.0, 11.9 (arom C), 55.4, 55.2 (CH),

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51.6 (OMe), 36.4, 36.3 (N-Me), 27.9, 27.2 (Ac), 14.0, 13.6 (Me) ppm. HRMS (acetone/NBA) calcd for
C13H18NO3 236.1287 (M+H). Found 236.1289.
N-Ethyl-2-methyl-3-oxo-N-phenylbutanamide (6j).16o Yield 95%. Yellow liquid. IR (CHCl3): " 1719
(C=O), 1647 (CONH) cm-1. 1H NMR (300 MHz, CDCl3): ! 7.49-7.37 (3H, m, arom H), 7.20-7.16 (2H, m,
arom H), 3.78 (2H, q, J = 6.0 Hz, N-CH2-Me), 3.32 (1H, q, J = 6.9 Hz, CH), 2.02 (3H, s, Ac), 1.25 (3H,
d, J = 6.9 Hz, Me), 1.15 (3H, t, J = 6.0 Hz, Me) ppm. 13C NMR (75 MHz, CDCl3): ! 204.9 (C=O), 170.1
(N-C=O), 141.9, 130.0, 128.6, 128.4 (arom C), 51.9 (CH), 44.4 (N-CH2), 27.9 (Ac), 13.8 (Me), 12.9 (Me)
ppm. FAB HRMS (acetone/NBA) calcd for C13H18NO2 220.1338 (M+H). Found 220.1335.
N-Butyl-2-methyl-3-oxo-N-phenylbutanamide (6k). Yield 67%. Orange liquid. IR (CHCl3): " 1718
(C=O), 1647 (CONH) cm-1. 1H NMR (300 MHz, CDCl3): ! 7.47-7.36 (3H, m, arom H), 7.19-7.15 (2H, m,
arom H), 3.72 (2H, t, J = 6.0 Hz, N-CH2), 3.32 (1H, q, J = 6.0 Hz, CH), 2.01 (3H, s, Ac), 1.51 (2H, quint,
J = 6.0 Hz, CH2), 1.33 (2H, sext, J = 6.0 Hz, CH2), 1.25 (3H, d, J = 6.0Hz, Me), 0.90 (3H, t, J = 6.0 Hz,
Me) ppm. 13C NMR (75 MHz, CDCl3): ! 204.9 (C=O), 170.3 (N-C=O), 142.1, 130.0, 128.5, 128.4 (arom
C), 51.9 (CH), 49.3 (N-CH2), 29.8 (CH2), 28.0 (Me), 20.0 (CH2), 13.9 (Me), 13.8 (Me ) ppm. FAB HRMS
(acetone/NBA) calcd for C15H22NO2 248.1651 (M+H). Found 248.1642.
N-Isopropyl-2-methyl-3-oxo-N-phenylbutanamide (6l). Yield 90%. Yellow liquid. IR (CHCl3): " 1719
(C=O), 1643 (CONH) cm-1. 1H NMR (300 MHz, CDCl3): ! 7.45-7.7.43 (3H, m, arom H), 7.27-7.12 (2H,
m, arom H), 5.01 (1H, q, J = 6.9 Hz, N-CH), 3.17 (1H, q, J = 9.0 Hz, CH), 1.99 (3H, s, Ac), 1.23 (3H, d, J
13
= 6.9 Hz, Me), 1.12 (3H, d, J = 7.2 Hz, Me), 1.04 (3H, d, J = 7.2 Hz, Me) ppm. C NMR (75 MHz,
CDCl3): ! 205.0 (C=O), 170.0 (N-C=O), 138.2, 130.5, 130.4, 129.5 (arom C), 52.5 (CH), 46.3 (N-CH),
28.0 (Ac), 21.1, 20.8, 13.9 (Me) ppm. FAB HRMS (acetone/NBA) calcd for C14H20NO2 234.1494 (M+H).
Found 234.1488.
2-Methyl-3-oxo-N,N-diphenylbutanamide (6m).20 Yield quant. Colorless prisms (from EtOH), mp
1
73-74 °C. IR (CHCl3): " 1724 (C=O), 1664 (CONH) cm-1. H NMR (500 MHz, CDCl3): ! 7.44-7.19
(10H, m, arom H), 3.63 (1H, q, J = 7.0 Hz, CH), 2.07 (3H, s, Ac), 1.36 (3H, d, J = 7.0 Hz, Me) ppm. 13C
NMR (125 MHz, CDCl3): ! 204.7 (C=O), 170.8 (>N-CO, 1C), 142.4, 130.1, 129.2, 128.9, 128.4, 126.3
(arom C), 52.4 (CH), 28.1 (Ac), 13.9 (Me) ppm.
2-Ethyl-N-methyl-3-oxo-N-phenylbutanamide (6n).19 Yield 48%. Yellow liquid. IR (CHCl3): " 1717
(C=O), 1651 (CONH) cm-1. 1H NMR (300 MHz, CDCl3): ! 7.48-7.36 (3H, m, arom H), 7.20-7.17 (2H, m,
arom H), 3.32 (3H, s, N-Me), 3.27 (1H, t, J = 6.0 Hz, CH), 2.06 (3H, s, Ac), 1.99-1.72 (2H, m, CH2-Me),
13
0.85 (3H, t, J = 7.2 Hz, Me) ppm. C NMR (75 MHz, CDCl3): ! 204.9 (C=O), 169.3 (N-C=O), 143.4,
130.0, 128.3, 127.7 (arom C), 59.2 (CH), 37.7 (N-Me), 28.1 (Ac), 23.0 (CH2), 12.3 (Me) ppm.
N-Methyl-3-oxo-N-phenyl-2-propylbutanamide (6o).19 Yield 47%. Brown liquid. IR (CHCl3): " 1716
(C=O), 1651 (CONH) cm-1. 1H NMR (500 MHz, CDCl3): ! 7.46-7.43 (2H, m, arom H), 7.39-7.37 (1H, m

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arom H), 7.18-7.16 (2H, m, arom H), 3.36-3.33 (1H, m, CH), 3.31 (3H, s, N-Me), 2.02 (3H, s, Ac),
1.94-1.71 (1H, m, H-CH), 1.70-1.64 (1H, m, HC-H), 1.30-1.24 (1H, m, H-CH), 1.20-1.13 (1H, m, HC-H),
13
0.82 (3H, t, J = 7.5 Hz, Me) ppm. C NMR (125 MHz, CDCl3): ! 205.0 (C=O), 169.5 (N-C=O), 143.4,
130.0, 128.3, 127.7 (arom C), 57.6 (CH), 37.7 (N-Me), 31.7, 21.0 (CH2), 28.1 (Ac), 13.9 (Me) ppm.
2-Isopropyl-N-methyl-3-oxo-N-phenylbutanamide (6p). Yield 43%. Brown liquid. IR (CHCl3): " 1717
(C=O), 1651 (CONH) cm-1. 1H NMR (500 MHz, CDCl3): ! 7.46-7.43 (2H, m, arom H), 7.39-7.36 (1H, m
arom H), 7.13-7.11 (2H, m, arom H), 3.30 (3H, s, N-Me), 3.05 (1H, d, J = 10.5 Hz, CH), 2.50 (1H, m,
13
CH), 2.17 (3H, s, Ac), 0.92 (3H, d, J = 7.0 Hz, Me), 0.75 (3H, d, J = 7.0 Hz, Me) ppm. C NMR (125
MHz, CDCl3): ! 205.0 (C=O), 168.7 (N-C=O), 143.3, 129.9, 128.2, 127.9 (arom C), 66.1 (CH), 37.8
(N-Me), 30.3 (Ac), 27.6 (CH), 21.0, 20.1 (Me) ppm. FAB HRMS (acetone/NBA) calcd for C14H20NO2
234.1494 (M+H). Found 234.1499.
2-Butyl-N-methyl-3-oxo-N-phenylbutanamide (6q).19 Yield 33%. Orange liquid. IR (CHCl3): " 1720
(C=O), 1651 (CONH) cm-1. 1H NMR (500 MHz, CDCl3): ! 7.46-7.43 (2H, m, arom H), 7.39-7.36 (1H, m
arom H), 7.18-7.16 (2H, m, arom H), 3.34-3.30 (1H, m, CH), 3.31 (3H, s, N-Me), 2.06 (3H, s, Ac),
1.93-1.87 (1H, m, H-CH), 1.73-1.68 (1H, m, HC-H), 1.26-1.18 (2H, m, CH2), 1.14-1.08 (2H, m, CH2),
13
0.85 (3H, t, J = 7.0 Hz, Me) ppm. C NMR (125 MHz, CDCl3): ! 205.0 (C=O), 169.5 (N-C=O), 143.4,
130.0, 128.3, 127.8 (arom C), 57.8 (CH), 37.7 (N-Me), 28.0 (Ac), 29.8, 29.3, 22.4 (CH2), 13.7 (Me) ppm.
N,2-Dimethyl-N-(1-naphthyl)-3-oxobutanamide (6r). Rotamer ratio = 1.2:1. Yield 77%. Colorless
1
microcystals (from EtOH), mp 79 °C. IR (CHCl3): " 1719 (C=O), 1651 (CONH) cm-1. H NMR (300
MHz, CDCl3): ! 7.92-7.31 (7H, m, arom H), 3.42 (3H, s, NMe), 3.18-3.13 (1H, m, CH), 1.97, 1.95 (3H, s,
Ac), 1.26, 1.19 (3H, d, J = 6.9 Hz, Me) ppm. 13C NMR (75 MHz, CDCl3): ! 205.1, 203.8 (C=O), 171.9,
171.0 (N-C=O), 139.4, 139.2, 134.7, 134.6, 129.9, 129.8, 129.2, 129.0, 128.8, 128.7, 127.7, 127.6, 127.0,
126.9, 126.0, 125.8, 125.7, 125.5, 122.2, 121.8 (arom C), 51.7, 51.4 (CH), 37.2 (N-Me), 28.0, 27.8 (Ac),
14.2, 14.1 (Me) ppm. MS (rel intensity): m/z 255 (45), 157 (100), 128 (40), 112 (80), 70 (45). Anal. Calcd
for C16H17NO2: C, 75.27; H, 6.71; N, 5.49. Found: C, 75.28; H, 6.92; N, 5.52.
N,2-Dimethyl-N-(2-naphthyl)-3-oxobutanamide (6s). Yield 79%. Colorless microcystals (from EtOH),
1
mp 103 °C. IR (CHCl3): " 1726 (C=O), 1654 (CONH) cm-1. H NMR (300 MHz, CDCl3): ! 7.96-7.85
(3H, m, arom H), 7.71 (1H, m, aron H), 7.56-7.53 (2H, m, arom H), 7.35-7.31 (1H, m, arom H), 3.49 (1H,
q, J = 6.9 Hz, CH), 3.39 (3H, s, NMe), 2.00 (3H, s, Ac), 1.28 (3H, d, J = 6.9 Hz, Me) ppm. 13C NMR (75
MHz, CDCl3): ! 204.1 (C=O), 170.3 (N-C=O), 140.3, 133.1, 132.0, 129.9, 127.4, 127.3, 126.7, 126.6,
125.6, 124.6 (arom C), 51.3 (CH), 37.1 (N-Me), 27.6 (Ac), 13.3 (Me) ppm. MS m/z (rel intensity): 255
(55, M+), 157 (100), 127 (35), 112 (30). Anal. Calcd for C16H17NO2: C, 75.27; H, 6.71; N, 5.49. Found: C,
75.11; H, 6.91; N, 5.47.

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Oxidation of 3-Oxo-N-phenylbutanamides 1a-c in Acetic Acid. To a 3-oxo-N-phenylbutanamide 1
(0.5 mmol) dissolved in glacial AcOH (15 mL) was added Mn(OAc)3•2H2O (1 or 2 mmol), and the
mixture was degassed under reduced pressure for 30 min using an ultrasonicator for exchange with an
argon atmosphere. The mixture was heated under reflux in an argon atmosphere until the brown color of
Mn(III) disappeared (normally 1 or 2 min). The mixture was concentrated under reduced pressure and 2M
HCl (20 mL) was added. The aqueous solution was then extracted three times with CHCl3 (20 mL x 3).
The combined extracts were washed with a saturated aqueous solution of NaHCO3 and water, dried over
anhydrous MgSO4, and then concentrated to dryness, giving an intractable mixture and no isolated
products were obtained except for a small amount of unchanged 1.
Mn(III)-Based Oxidation of 3-Oxo-N-phenylbutanamide 1a (R = H) in the Presence of Alkene as a
Radical Trapping Reagent.21 To a mixture of 3-oxobutanamide 1a (0.177 g; 1 mmol) and
1,1-diphenylethene (0.180 g; 1 mmol) in glacial AcOH (15 mL) was added Mn(OAc)3•2H2O (0.992 g; 4
mmol), then the mixture was heated under reflux until the brown color of Mn(III) disappeared (for 1 min).
After the work-up described above, 2-methyl-N,5,5-triphenyl-4,5-dihydrofuran-3-carboxamide (VI) was
obtained in 0.155 g (43% yield) as a colorless solid which was recrystallized using CHCl3–hexane.
2-Methyl-N,5,5-triphenyl-4,5-dihydrofuran-3-carboxamide
(VI).
Colorless
needles
(from
1
CHCl3-hexane), mp 248-251 °C. IR (CHCl3): " 3400-3200 (NH), 1662 (C=O), 1632 (C=C) cm-1. H
NMR (500 MHz, CDCl3): ! 7.50-7.48 (2H, m, arom H), 7.42-7.40 (4H, m, arom H), 7.38-7.34 (4H, m,
arom H), 7.31-7.26 (4H, m, arom H), 7.09-7.06 (1H, m, aron H), 6.84 (1H, s, NH), 3.68 (1H, s, CH2),
2.45 (3H, s, Me) ppm. 13C NMR (125 MHz, CDCl3): ! 163.6 (C=O), 152.6 (C-2), 144.9, 138.0 (arom C),
128.9, 128.5, 127.7, 125.7, 124.0, 120.0 (arom CH), 102.7 (C-3), 90.9 (C-5), 44.7 (C-4), 14.3 (Me) ppm.
MS m/z (rel internsity): 355 (33, M+), 313 (40), 262 (100), 247 (70), 221 (45), 191 (90), 175 (40), 165
(75), 115 (70), 105 (3), 93 (60), 77 (70). Anal. Calcd for C24H21NO2•1/10H2O: C, 80.70; H, 5.93; N, 3.92.
Found: C, 80.58; H, 5.96; N, 3.97.
Oxidation of N-Methyl-3-oxo-N-phenylbutanamide (1b) in Ethanol. A mixture of butanamide 1b (3
mmol) and Mn(OAc)3•2H2O (12 mmol) in EtOH (60 mL) was degassed under reduced pressure for 20
min using an ultrasonicator for exchange with an argon atmosphere and then heated under reflux until the
brown color of Mn(III) disappeared (for 4 min). 2M HCl (25 mL) was added to the reaction mixture and
the aqueous solution was extracted three times with CH2Cl2 (25 mL x 3). The combined extracts were
washed with a saturated aqueous solution of NaHCO3, dried over anhydrous MgSO4, and then
concentrated to dryness. The residue was separated on silica gel TLC (Wako B-10) while eluting with
Et2O, affording the dimeric 3,3'-biindoline-2,2'-dione derivatives 3, 4, and 5. The analytical samples were
further purified by recrystallization from the solvent specified in parentheses and their physical data are
listed below.

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553
3,3'-Diacetyl-1,1'-dimethyl-[3,3'-biindoline]-2,2'-dione (3). Yield 9%. Colorless microcrystals (from
1
EtOH), mp 176-177 °C. IR (KBr): " 1728 (C=O), 1686 (CONH) cm-1. H NMR (300 MHz, CDCl3): !
7.31-7.26 (4H, m, arom H), 7.00-6.95 (2H, m arom H), 6.75-6.72 (2H, m, arom H), 3.19 (6H, s, N-Me),
2.10 (6H, s, Ac) ppm. 13C NMR (75 MHz, CDCl3): ! 199.3 (C=O), 171.9 (N-C=O), 144.4, 129.8, 127.2,
123.7, 122.4, 108.2 (arom C), 69.3 (>C<), 28.5 (N-Me), 26.7 (Ac) ppm. FAB HRMS (acetone/NBA)
calcd for C22H21N2O4 377.1501 (M+H). Found 377.1517.
1,1'-Dimethyl-[3,3'-biindoline]-2,2'-dione (4). A 1:1 diastereomer mixture. Yield 7%. Colorless
1
microcrystals (from EtOH), mp 197-198 °C (lit,22 mp 194-196 °C). IR (KBr): " 1720 (CONH) cm-1. H
NMR (300 MHz, CDCl3): ! 7.29-7.27 (1H, m, arom H), 7.11-7.08 (1H, m arom H), 6.95-6.90 (2H, m,
arom H), 6.82-6.75 (3H, m, arom H), 6.70-6.67 (1H, m, arom H), 4.29 (1H, s, CH), 4.18 (1H, s, CH’),
13
3.28 (3H, s, N-Me), 3.12 (3H, s, N-Me’) ppm. C NMR (75 MHz, CDCl3): ! 175.9, 174.7 (N-C=O),
145.0, 144.2, 128.8, 128.4, 125.8, 124.8, 123.3, 123.2, 122.5, 122.4, 108.3, 108.0 (arom C), 46.2, 46.1
(CH), 26.3, 26.2 (N-Me) ppm. MS m/z (rel intensity): 292 (20, M+), 146 (100), 118 (18), 91 (35), 77 (12),
65 (12), 51 (13).
(E)-1,1'-Dimethyl-[3,3'-biindolinylidene]-2,2'-dione (5).23 Yield 32%. Reddish prisms (from EtOH),
mp 275-276 °C (lit, mp 278 °C, 23a 274-275 °C23d). IR (KBr): " 1680 (CONH) cm-1. 1H NMR (300 MHz,
CDCl3): ! 9.20 (2H, d, J = 7.8 Hz, H-4 and H-4’), 7.4 (2H, t, J = 7.5 Hz, H-6 and H-6’), 7.07 (2H, t, J =
13
7.5 Hz, H-5 and H-5’), 6.79 (2H, d, J = 7.8 Hz, H-7 and H-7’), 3.29 (6H, s, N-Me) ppm. C NMR (75
MHz, CDCl3): ! 168.0 (N-C=O), 145.2, 132.4, 129.8, 122.4, 121.6, 107.7 (arom C), 26.1 (N-Me) ppm.
MS m/z (rel intensity): 290 (100, M+), 262 (45), 233 (50), 218 (30), 146 (20), 117 (25).
Oxidation of N,2-Disubstituted N-Aryl-3-oxobutanamides 6a-s in Acetic Acid. The general
procedure for the reaction of 3-oxobutanamides 6a-s with Mn(OAc)3•2H2O was as follows. To
3-oxobutanamide 6 (0.5 mmol) dissolved in glacial AcOH (15 mL) was added Mn(OAc)3•2H2O (1 mmol).
The mixture was quickly heated under reflux using a pre-heated oil bath at 140 °C until the brown color
of Mn(III) disappeared (normally within 3-5 min). The solvent was removed under reduced pressure and
the residue was triturated with 2M HCl (15 mL). The aqueous mixture was extracted three times with
CHCl3 (20 mL x 3), and the combined extracts were washed with a saturated aqueous solution of
NaHCO3 and water, dried over anhydrous MgSO4, and then concentrated to dryness, giving the desired
acetylindolinone 7. If needed, the obtained acetylindolinone 7 was purified by silica gel TLC eluting with
Et2O–hexane (7:3 v/v) and the solid 7 was recrystallized from the appropriate solvent as mentioned below.
When the separation of the product 7 was performed using neutral Al2O3 eluting with Et2O–hexane (7:3
v/v), deacetylated indolinone 8 was obtained (vide infra).
1
3-Acetyl-1,3-dimethylindolin-2-one (7a).16g,24 Yield quant. IR (CHCl3): " 1720, 1709 (C=O) cm-1. H
NMR (300 MHz, CDCl3): ! 7.35 (1H, t, J = 7.2 Hz, arom H), 7.16 (1H, d, J = 7.2 Hz, arom H), 7.09 (1H,

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t, J = 7.2 Hz, arom H), 6.92 (1H, d, J = 7.2 Hz, arom H), 3.30 (3H, s, Me), 1.97 (3H, s, Ac), 1.58 (3H, s,
Me) ppm. 13C NMR (75 MHz, CDCl3): ! 201.0, 175.9 (C=O), 143.7, 129.4 (arom C), 129.2, 123.5, 123.3,
108.6 (arom CH), 62.0 (C-3), 26.6 (Me), 25.9 (Me), 18.9 (Me) ppm.
3-Acetyl-5-fluoro-1,3-dimethylindolin-2-one (7b). Yield 99%. Yellow liquid. IR (CHCl3): " 1728, 1707
(C=O) cm-1. 1H NMR (500 MHz, CDCl3): ! 6.98 (1H, dt, J = 8.5, 2.5 Hz, arom H), 6.86 (1H, dd, J = 8.5,
2.5 Hz, arom H), 6.77 (1H, dd, J = 8.5, 4.0 Hz, arom H), 3.22 (3H, s, Me), 1.94 (3H, s, Me), 1.51 (3H, s,
Me). 13C NMR (125MHz, CDCl3): ! 200.5, 175.4 (C=O), 159,4 (d, 1J = 242.2 Hz), 139.5, 130.8 (d, 3J =
8.3 Hz) (arom C), 115.4 (d, 2J = 22.8 Hz), 111.9 (d, 2J = 25.2 Hz), 109.0 (d, 3J = 8.4 Hz) (arom CH), 62.2
(C-3), 26.7, 25.9, 19.2 (Me). FAB HRMS (acetone/NBA) calcd for C12H13FNO2 222.0930 (M+H). Found
222.0929.
3-Acetyl-5-chloro-1,3-dimethylindolin-2-one (7c). Yield quant. Colorless microcrystals (from hexane),
mp 80-83 °C. IR (CHCl3): " 1728, 1713 (C=O) cm-1. 1H NMR (300 MHz, CDCl3): ! 7.33 (1H, dd, J = 8.1,
1.8, Hz, H-6), 7.16 (1H, d, J = 1.8 Hz, H-4), 6.84 (1H, d, J = 8.1 Hz, H-7), 3.23 (3H, s, Me), 2.02 (3H, s,
Me), 1.58 (3H, s, Me). 13C NMR (75MHz, CDCl3): ! 200.3, 175.4 (C=O), 142.2, 130.9, 129.1 (arom C),
128.6, 124.2, 109.5 (arom CH), 62.0 (C-3), 26.8, 26.0, 19.3 (Me). Anal. Calcd for C12H12ClNO2: C,
60.49; H, 5.09; N, 5.89. Found: C, 60.41; H, 5.04; N, 5.96.
3-Acetyl-7-chloro-1,3-dimethylindolin-2-one (7d). Yield quant. Orange liquid. IR (CHCl3): " 1717
(C=O) cm-1. 1H NMR (300 MHz, CDCl3): ! 7.29-7.26 (1H, m, arom H), 7.05-6.97 (2H, m, arom H), 3.66
(3H, s, Me), 1.99 (3H, s, Me), 1.57 (3H, s, Me). 13C NMR (75MHz, CDCl3): ! 200.3, 176.1 (C=O), 131.9
(arom C), 131.4, 124.0 (2C), 122.1 (arom CH), 115.9 (arom C), 61.7 (C-3), 30.0, 26.0, 19.5 (Me). FAB
HRMS (acetone/NBA/NaI) calcd for C12H12ClNO2Na 260.0454 (M+Na). Found 260.0454.
3-Acetyl-1,3,5-trimethylindolin-2-one (7e). Yield quant. Colorless prisms (from EtOH), mp 92-95 °C
(lit,16j,24 mp 90-93 °C). IR (CHCl3): " 1724, 1701 (C=O) cm-1. 1H NMR (300 MHz, CDCl3): ! 7.16 (1H,
dd, J = 7.5, 0.6, Hz, H-6), 6.94 (1H, d, J = 0.6 Hz, H-4), 6.80 (1H, d, J = 7.5 Hz, H-7), 3.28 (3H, s, Me),
2.33 (3H, s, Me), 1.94 (3H, s, Me), 1.58 (3H, s, Me). 13C NMR (75MHz, CDCl3): ! 201.2, 175.9 (C=O),
141.3, 132.3 (2C) (arom C), 129.4, 124.3, 108.6 (arom CH), 62.1 (C-3), 26.7, 25.9, 21.1, 18.9 (Me). Anal.
Calcd for C13H15NO2: C, 71.87; H, 6.96; N, 6.45. Found: C, 71.74; H, 7.04; N, 6.55.
3-Acetyl-1,3,7-trimethylindolin-2-one (7f).24 Yield 94%. Colorless microcrystals (from EtOH), mp
1
80-83 °C (lit,16j mp 79-81 °C). IR (CHCl3): " 1724, 1701 (C=O) cm-1. H NMR (300 MHz, CDCl3): !
7.09-7.06 (1H, m, arom H), 6.97-6.95 (2H, m, arom H), 3.58 (3H, s, Me), 2.62 (3H, s, Me), 1.95 (3H, s,
Me), 1.54 (3H, s, Me). 13C NMR (75MHz, CDCl3): ! 201.1, 176.6 (C=O), 141.5, 130.0, 120.2 (arom C),
132.8, 123.1, 121.4 (arom CH), 61.5 (C-3), 29.9, 25.8, 19.3, 19.0 (Me). Anal. Calcd for C13H15NO2: C,
71.87; H, 6.96; N, 6.45. Found: C, 71.73; H, 7.07; N, 6.37.

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3-Acetyl-5-methoxy-1,3-dimethylindolin-2-one (7g). Yield 89%. Colorless microcrystals (from hexane),
mp 89-92 °C. IR (CHCl3): " 1724, 1701 (C=O) cm-1. 1H NMR (300 MHz, CDCl3): ! 6.88 (1H, dd, J = 8.4,
2.1, Hz, H-6), 6.826 (1H, d, J = 8.4 Hz, H-7), 6.764 (1H, d, J = 2.1 Hz, H-4), 3.80 (3H, s, MeO), 3.22 (3H,
13
s, Me), 1.97 (3H, s, Me), 1.57 (3H, s, Me). C NMR (75MHz, CDCl3): ! 201.1, 175.6 (C=O), 156.5,
137.1, 130.6 (arom C), 113.7, 110.6, 109.0 (arom CH), 62.4 (C-3), 55.9 (MeO), 26.7, 25.9, 19.0 (Me).
Anal. Calcd for C13H15NO3: C, 66.94; H, 6.48; N, 6.00. Found: C, 66.80; H, 6.59; N, 6.00.
A
Mixture of 3-Acetyl-6-methoxy-1,3-dimethylindolin-2-one and 3-Acetyl-4-methoxy-1,3-
dimethylindolin-2-one (7h). 6-Mthoxy-7h:4-methoxy-7h = 1.8:1. Yield 83%. Colorless microcrystals
1
(from hexane), mp 100-103 °C. IR (CHCl3): " 1730, 1701 (C=O) cm-1. H NMR (500 MHz, CDCl3): !
7.35-7.30 (m, arom H), 7.04 (d, J = 8.0 Hz, arom H), 6.67 (d, J = 8.0 Hz, arom H), 6.61-6.58 (m, arom H),
6.52 (d, J = 1.5 H, arom H), 3.85, 3.82 (s, MeO), 3.28, 3.27 (s, Me), 1.95, 1.92 (s, Me), 1.61, 1.54 (s, Me).
13C NMR (75MHz, CDCl3): ! 201.1, 200.3, 176.3, 174.9 (C=O), 160.9, 155.6, 145.0, 144.9, 121.1, 116.2
(arom C), 130.3, 124.0, 106.9, 106.1, 101.7, 96.6 (arom CH), 61.5, 61.3 (C-3), 55.5, 55.4 (MeO), 26.8,
26.5, 25.6, 25.5, 18.8, 16.7 (Me). Anal. Calcd for C13H15NO3: C, 66.94; H, 6.48; N, 6.00. Found: C,
66.77; H, 6.54; N, 5.97.
3-Acetyl-7-methoxy-1,3-dimethylindolin-2-one (7i). Yield 89%. Brown liquid. IR (CHCl3): " 1724,
1
1701 (C=O) cm-1. H NMR (300 MHz, CDCl3): ! 7.03 (1H, t, J = 8.1 Hz, H-5), 6.91 (1H, br. d, J = 8.1
Hz, H-6), 6.75 (1H, br. d, J = 7.8 Hz, H-4), 3.89 (3H, s, MeO), 3.56 (3H, s, Me), 1.95 (3H, s, Me), 1.54
13
(3H, s, Me). C NMR (75MHz, CDCl3): ! 201.0, 176.0 (C=O), 145.5, 131.5, 130.9, (arom C), 123.7,
116.0, 112.8 (arom CH), 62.2 (C-3), 56.0 (MeO), 29.9, 25.8, 19.0 (Me). FAB HRMS (acetone/NBA/NaI)
calcd for C13H15NO3Na 256.0950 (M+Na). Found 256.0959.
3-Acetyl-1-ethyl-3-methylindolin-2-one (7j). Yield 96%. Orange liquid. IR (CHCl3): " 1724, 1705
(C=O) cm-1. 1H NMR (300 MHz, CDCl3): ! 7.34 (1H, dd, J = 7.8, 1.2 Hz, arom H), 7.15 (1H, m, arom H),
7.08 (1H, br. t, J = 7.5 Hz, arom H9, 6.94 (1H, br. d, J = 7.8 Hz, arom H), 3.96-3.73 (2H, m, -CH2-CH3),
13
1.95 (3H, s, Me), 1.57 (3H, s, Me), 1.32 (3H, t, J = 7.2 Hz, -CH2-CH3). C NMR (75MHz, CDCl3): !
201.0, 175.5 (C=O), 142.8, 129.7 (arom C), 129.1, 123.7, 123.0, 108.7 (arom CH), 62.0 (C-3), 35.0
(N-CH2), 25.8, 18.7 (Me), 12.5 (N-CH2-CH3). FAB HRMS (acetone/NBA/NaI) calcd for C13H15NO2Na
240.1000 (M+Na). Found 240.1004.
3-Acetyl-1-butyl-3-methylindolin-2-one (7k). Yield 98%. Orange liquid. IR (CHCl3): " 1724, 1705
1
(C=O) cm-1. H NMR (300 MHz, CDCl3): ! 7.36-7.30 (1H, m, arom H), 7.16-7.14 (1H, m, arom H),
7.10-7.05 (1H, m, arom H), 6.92 (1H, br. d, J = 6.6 Hz, arom H), 3.87-3.69 (2H, m, N-CH2-CH2CH2CH3),
1.96 (3H, s, Me), 1.71 (2H, quint, J = 7.2 Hz, N-CH2-CH2-CH2CH3), 1.56 (3H, s, Me), 1.43 (2H, sex, J =
7.2 Hz, N-CH2CH2-CH2-CH3), 0.98 (3H, t, J = 7.2 Hz, N-CH2CH2CH2-CH3). 13C NMR (75MHz, CDCl3):
! 201.1, 175.8 (C=O), 143.2, 129.6 (arom C), 129.1, 123.7, 123.0, 108.9 (arom CH), 61.9 (C-3), 40.1

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(N-CH2-CH2CH2CH3), 29.4 (CH2), 25.9 (Me), 20.2 (CH2), 18.9 (Me), 13.7 (Me). FAB HRMS
(acetone/NBA/NaI) calcd for C15H19NO2Na 268.1313 (M+Na). Found 268.1312.
3-Acetyl-1-isopropyl-3-methylindolin-2-one (7l). Yield 93%. Orange liquid. IR (CHCl3): " 1724, 1701
(C=O) cm-1. 1H NMR (500 MHz, CDCl3): ! 7.31 (1H, br. t, J = 8.0 Hz, arom H), 7.13 (1H, br. d, J = 7.0
Hz, arom H), 7.07 (2H, br. t, J = 7.5 Hz, arom H), 4.68 (1H, sep, J = 7.0 Hz, N-CHMe2), 1.93 (3H, s, Me),
1.55 (3H, s, Me), 1.54 (3H, d, J = 7.0 Hz, Me), 1.53 (3H, d, J = 7.0 Hz, Me). 13C NMR (75MHz, CDCl3):
! 200.9, 175.6 (C=O), 142.5, 129.8 (arom C), 128.8, 123.7, 122.7, 110.2 (arom CH), 61.9 (C-3), 44.2
(CH), 25.6 (Me), 19.3 (Me), 19.2 (Me), 18.7 (Me). FAB HRMS (acetone/NBA/NaI) calcd for
C14H17NO2Na 254.1157 (M+Na). Found 254.1158.
3-Acetyl-3-methyl-1-phenylindolin-2-one (7m). Yield 91%. Colorless needles (from EtOH), mp
112-115 °C (lit,24d) mp 101-103 °C). IR (CHCl3): " 1728, 1710 (C=O) cm-1. 1H NMR (500 MHz, CDCl3):
! 7.56 (2H, d, J = 7.5 Hz, arom H), 7.46-7.44 (3H, m, arom H), 7.28 (1H, t, J = 7.5 Hz, arom H), 7.22
(1H, d, J = 6.5 Hz, arom H), 7.13 (1H, t, J = 8.0 Hz, arom H), 6.90 (1H, d, J = 8.0 Hz, arom H), 2.11 (3H,
13
s, Me), 1.70 (3H, s, Me). C NMR (125MHz, CDCl3): ! 200.7, 175.3 (C=O), 143.7, 134.1, 129.2 (arom
C), 129.8, 129.1, 128.4, 126.4, 123.8, 123.7, 109.9 (arom CH), 62.1 (C-3), 26.0 (Me), 19.2 (Me). Anal.
Calcd for C17H15NO2: C, 76.96; H, 5.70; N, 5.28. Found: C, 76.99; H, 5.68; N, 5.30.
3-Acetyl-3-ethyl-1-methylindolin-2-one (7n).16g Yield 98%. Orange liquid. IR (CHCl3): " 1719, 1705
(C=O) cm-1. 1H NMR (300 MHz, CDCl3): ! 7.30-7.25 (1H, m, arom H), 7.10 (1H, d, J = 7.5 Hz, arom H),
7.03 (1H, t, J = 7.5 Hz, arom H), 6.83 (1H, d, J = 8.0 Hz, arom H), 3.22 (3H, s, Me), 2.21-2.07 (2H, m,
13
CH2-CH3), 1.94 (3H, s, Me), 0.53 (3H, t, J = 7.5 Hz, CH2-CH3). C NMR (75MHz, CDCl3): ! 201.4,
175.0 (C=O), 144.3, 127.2 (arom C), 129.0, 123.9, 123.1, 108.3 (arom CH), 67.3 (C-3), 26.6 (Me x 2),
26.4 (CH2), 8.1 (Me). FAB HRMS (acetone/NBA/NaI) calcd for C13H15NO2Na 240.1000 (M+Na). Found
240.1000.
3-Acetyl-1-methy-3-propylindolin-2-one (7o). Yield 94%. Orange liquid. IR (CHCl3): " 1722, 1705
1
(C=O) cm-1. H NMR (500 MHz, CDCl3): ! 7.35 (1H, t, J = 7.5 Hz, arom H), 7.17 (1H, d, J = 7.5 Hz,
arom H), 7.10 (1H, t, J = 7.5 Hz, arom H), 6.90 (1H, d, J = 7.5 Hz, arom H), 3.29 (3H, s, Me), 2.20-2.08
(2H, m, CH2-CH2CH3), 2.00 (3H, s, Me), 1.05-0.97 (2H, m, CH2-CH2-CH3), 0.82 (3H, t, J = 6.0 Hz,
CH2CH2-CH3). 13C NMR (125MHz, CDCl3): ! 201.3, 175.2 (C=O), 144.2, 127.6 (arom C), 129.0, 123.9,
123.1, 108.4 (arom CH), 66.8 (C-3), 35.5 (CH2), 26.5 (Me), 26.4 (Me), 17.2 (CH2), 14.1 (Me). FAB
HRMS (acetone/NBA/NaI) calcd for C14H17NO2Na 254.1157 (M+Na). Found 254.1157.
3-Acetyl-3-isopropyl-1-methylindolin-2-one (7p). Yield 4%. Orange liquid. IR (CHCl3): " 1722, 1707
1
(C=O) cm-1. H NMR (500 MHz, CDCl3): ! 7.34 (1H, dt, J = 7.5, 1.0 Hz, arom H), 7.28 (1H, d, J = 7.5
Hz, arom H), 7.10 (1H, t, J = 7.5 Hz, arom H9, 6.87 (1H, d, J = 7.5 Hz, arom H), 3.26 (3H, s, Me), 2.84
(1H, sep, J = 7.0 Hz, CHMe2), 2.17 (3H, s, Me), 0.89 (3H, d, J = 7.0 Hz, Me), 0.84 (3H, d, J = 7.0 Hz,

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13
Me). C NMR (125MHz, CDCl3): ! 202.3, 174.3 (C=O), 144.0, 129.5, (arom C), 128.7, 125.2, 122.8,
108.0 (arom CH), 70.4 (C-3), 34.5 (CH), 27.7 (Me), 26.3 (Me), 17.5 (Me), 17.1 (Me). FAB HRMS
(acetone/NBA/NaI) calcd for C14H18NO2 232.1338 (M+H). Found 232.1335.
3-Acetyl-3-butyl-1-methylindolin-2-one (7q). Yield 81%. Colorless liquid. IR (CHCl3): " 1722, 1705
1
(C=O) cm-1. H NMR (500 MHz, CDCl3): ! 7.35 (1H, t, J = 7.5 Hz, arom H), 7.17 (1H, d, J = 7.5 Hz,
arom H), 7.104 (1H, t, J = 7.5 Hz, arom H), 6.91 (1H, d, J = 7.5 Hz, arom H), 3.30 (3H, s, Me), 2.22-2.11
(2H, m, CH2-CH2CH2CH3), 2.00 (3H, s, Me), 1.29-1.17 (2H, m, CH2 x 2), 1,00-0.91 (1H, m, CHH), 0.78
(3H, t, J = 7.5 Hz, N-CH2CH2CH2-CH3), 0.75-0.72 (1H, m, CHH). 13C NMR (125MHz, CDCl3): ! 201.4,
175.2 (C=O), 144.2, 127.6 (arom C), 129.0, 123.9, 123.2, 108.4 (arom CH), 66.7 (C-3), 33.1
(N-CH2-CH2CH2CH3), 26.5 (Me), 26.4 (Me), 25.8 (CH2), 22.7 (CH2), 13.8 (Me). FAB HRMS
(acetone/NBA/NaI) calcd for C15H19NO2Na 268.1313 (M+Na). Found 268.1316.
3-Acetoxy-3-butyl-1-methylindolin-2-one (9). Yield 60%. Colorless liquid. IR (CHCl3): " 1728 (C=O),
1244 (C-O-C) cm-1. 1H NMR (500 MHz, CDCl3): ! 7.32 (1H. t, J = 7.5 Hz, arom H), 7.21 (1H, d, J = 7.5
Hz, arom H), 7.05 (1H, t, J = 7.5 Hz, arom H), 6.84 (1H, d, J = 7.5 Hz, arom H), 3.29 (3H, s, Me), 2.04
(3H, s, Me), 2.00-1.90 (2H, m, N-CH2-CH2CH2CH3), 1.29-1.17 (3H, m, CHH-CH2CH3), 1.14-1.08 (1H,
m, CHH-CH2CH3), 0.83 (3H, t, J = 7.5 Hz, N-CH2CH2CH2-CH3). 13C NMR (125MHz, CDCl3): ! 175.2,
169.0 (C=O), 144.0, 127.9 (arom C), 129.6, 122.6, 122.5 108.3 (arom CH), 80.1 (C-3), 36.4
(N-CH2-CH2CH2CH3), 26.4 (Me), 24.1 (CH2), 22.7 (CH2), 20.7 (Me), 13.8 (Me). FAB HRMS
(acetone/NBA/NaI) calcd for C15H19NO3Na 284.1263 (M+Na). Found 284.1254.
3-Acetyl-1,3-dimethyl-1H-benzo[g]indol-2(3H)-one (7r). Yield 96%. Colorless microcrystals (from
EtOH), mp 128 °C. IR (CHCl3): " 1724, 1647 (C=O) cm-1. 1H NMR (300 MHz, CDCl3): ! 7.79 ( 1H, d, J
= 8.0 Hz, arom H), 7.58 (1H, d , J = 8.0 Hz, arom H), 7.50 (2H, t, J = 7.5 Hz, arom H), 7.15 (1H, d, J =
8.0 Hz, arom H), 7.07 (1H, d, J = 8.0 Hz, arom H), 3.60 (3H, s, Me), 2.05 (3H, s, Me), 1.78 (3H, s, Me).
13C NMR (75MHz, CDCl3): ! 201.3, 169.5 (C=O), 136.4, 133.7, 133.0, 118.8 (arom C), 127.2, 127.1,
126.8, 123.5, 123.0, 109.2 (arom CH), 60.9 (C-3), 29.6 (Me), 27.1 (Me), 26.9 (Me). Anal. Calcd for
C16H15NO2: C, 75.87; H, 5.97; N, 5.53. Found: C, 75.83; H, 6.11; N, 5.60.
1-Acetyl-1,3-dimethyl-1H-benzo[e]indol-2(3H)-one (7s). Yield 99%. Colorless microcrystals (from
EtOH), mp 132 °C. IR (CHCl3): " 1726, 1694 (C=O) cm-1. 1H NMR (300 MHz, CDCl3): ! 7.83 (1H, d, J
= 8.4 Hz, arom H), 7.75 (1H, d, J = 8.1 Hz, arom H), 7.48 (1H, d, J = 8.1 Hz, arom H), 7.35 (1H, t, J =
8.1 Hz, arom H), 7.24 (1H, t, J = 8.1 Hz, arom H), 7.17 (1H, d, J = 8.4 Hz, arom H), 3.30 (3H, s, Me),
1.74 (3H, s, Me), 1.66 (3H, s, Me). 13C NMR (75MHz, CDCl3): ! 201.0, 176.0 (C=O), 141.6, 130.4 (2C),
128.9 (arom C), 130.3, 129.3, 127.8, 124.0, 121.3, 109.5 (arom CH), 63.0 (C-3), 26.7 (Me), 25.7 (Me),
18.4 (Me). Anal. Calcd for C16H15NO2: C, 75.87; H, 5.97; N, 5.53. Found: C, 75.98; H, 6.14; N, 5.77.

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Deacetylation of 3-Actyl-1,3-dimethylindolin-2-ones 7. To the obtained dimethylindolinone 7 (0.5
mmol) in Et2O (30 mL) was added neutral Al2O3 (7 g) in a 100-mL round-bottomed flask, and stirred at
room temperature for 1 h. The reaction mixture was filtered using a 3G2 glass filter, washed with CHCl3,
and concentrated. The residue was again dissolved in CHCl3, washed with a saturated aqueous solution of
NaHCO3, water, dried over anhydrous MgSO4, and then concentrated to dryness. The crude deacetylated
indolinone 8 was separated by silica gel TLC eluting with hexane. The solid product 8 was recrystallized
from the appropriate solvent as mentioned below.
1,3-Dimethylindolin-2-one (8a).16a,16d,16n,25 Yield quant. Colorless prisms (from EtOH), mp 152 °C. IR
(CHCl3): " 1716 (C=O) cm-1. 1H NMR (300 MHz, CDCl3): ! 7.29 (1H, td, J = 7.5, 0.9 Hz, arom H), 7.24
(1H, d, J = 7.8 Hz, arom H), 7.06 (1H, dt, J = 7.5, 0.9 Hz, arom H), 6.83 (1H, d, J = 7.8 Hz, arom H),
3.44 (1H, q, J = 7.8 Hz, >CH-), 3.21 (3H, s, Me), 1.48 (3H, d, J = 7.8 Hz, Me) ppm. 13C NMR (75 MHz,
CDCl3): ! 178.7 (C=O), 143.9, 130.6 (arom C), 127.8, 123.4, 122.3, 107.9 (arom CH), 40.5 (C-3), 26.1
(Me), 15.3 (Me) ppm. MS m/z (rel intensity) 161 (M+, 70), 146 (45), 132 (10), 118 (100), 91 (20).
5-Fluoro-1,3-dimethylindolin-2-one (8b).16d Yield 72%. 1H NMR (500 MHz, CDCl3): ! 6.99-6.95 (2H,
m, arom H), 6.75-6.73 (1H, m, arom H), 3.42 (1H, q, J = 7.5 Hz, >CH-), 3.23 (3H, s, Me), 1.47 (3H, d, J
= 7.5 Hz, Me) ppm. 13C NMR (125 MHz, CDCl3): ! 178.0 (C=O), 159.1 (d, J = 238.5 Hz), 139.8, 132.1
(d, J = 8.4 Hz) (arom C), 113.7 (d, J = 23.9 Hz), 111.5 (d, J = 23.9 Hz), 108.2 (d, J = 8.4 Hz) (arom CH),
40.7 (C-3), 26.2 (Me), 15.1 (Me) ppm.
5-Chloro-1,3-dimethylindolin-2-one (8c).26 Yield 31%. Colorless prisms (from CHCl3-hexane), mp
1
66 °C. IR (CHCl3): " 1705 (C=O) cm-1. H NMR (300 MHz, CDCl3): ! 7.249 (1H, dd, J = 8.1, 2.4 Hz,
arom H), 7.25 (1H, d, J = 2.4 Hz, arom H), 6.74 (1H, d, J = 8.1 Hz, arom H), 3.42 (1H, q, J = 7.8 Hz,
>CH-), 3.19 (3H, s, Me), 1.47 (3H, d, J = 7.8 Hz, Me) ppm. 13C NMR (75 MHz, CDCl3): ! 178.0 (C=O),
142.5, 132.2, 127.7 (arom C), 127.7, 124.0, 108.8 (arom CH), 40.6 (C-3), 26.3 (Me), 15.2 (Me) ppm. MS
m/z (rel intensity) 197 (M+, 30), 195 (M+, 100), 180 (30), 160 (95), 152 (50), 117 (95), 89 (30). Anal.
Calcd for C10H10ClNO: C, 61.39; H, 5.15; N, 7.16. Found: C, 61.22; H, 5.04; N, 7.05.
5-Methoxy-1,3-dimethylindolin-2-one (8g).16d,27 Yield 96%. Yellow liquid. IR (CHCl3): " 1697 (C=O)
cm-1. 1H NMR (300 MHz, CDCl3): ! 6.86 (1H, m, arom H), 6.80 (1H, dd, J = 8.5, 2.5 Hz, arom H), 6.72
(1H, d, J = 8.5, arom H), 3.79 (3H, s, MeO), 3.39 (1H, q, J = 7.5 Hz, >CH-), 3.14 (3H, s, Me), 1.46 (3H, d,
J = 7.5 Hz, Me) ppm. 13C NMR (75 MHz, CDCl3): ! 178.2 (C=O), 155.9, 137.5, 132.0 (arom C), 111.9,
111.2, 108.1 (arom CH), 55.8 (MeO), 40.9 (C-3), 26.2 (Me), 15.4 (Me) ppm.
4-Methoxy-1,3-dimethylindolin-2-one (8h).28 Yield 76%. Colorless prisms (from CHCl3-hexane), mp
70 °C. IR (CHCl3): " 1705 (C=O) cm-1. 1H NMR (300 MHz, CDCl3): ! 7.22 (1H, t, J = 8.4 Hz, arom H),
6.62 (1H, d, J = 8.4 Hz, arom H), 6.47 (1H, d, J = 8.4 Hz, arom H), 3.84 (3H, s, MeO), 3.43 (1H, q, J =
7.5 Hz, >CH-), 3.16 (3H, s, Me), 1.49 (3H, d, J = 7.5 Hz, Me) ppm. 13C NMR (75 MHz, CDCl3): ! 178.6

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559
(C=O), 155.6, 144.8, 116.16 (arom C), 128.8, 105.3, 101.1 (arom CH), 55.0 (MeO), 39.3 (C-3), 26.0 (Me),
14.0 (Me) ppm. MS m/z (rel intensity) 191 (M+, 80), 176 (100), 148 (60), 133 (50), 117 (30), 105 (20), 91
(35), 77 (50).
1,3-Dimethyl-1H-benzo[g]indol-2(3H)-one (8r). Yield 63%. Colorless prisms (from CHCl3-hexane), mp
80-81 °C. IR (CHCl3): " 1665 (C=O) cm-1. 1H NMR (300 MHz, CDCl3): ! 7.71 (1H, d, J = 8.1 Hz, arom
H), 7.52-7.40 (3H, m, arom H), 7.31 (1H, d, J = 7.2 Hz, arom H), 6.94 (1H, d, J = 7.5 Hz, arom H), 4.14
13
(1H, q, J = 7.5 Hz, >CH-), 3.50 (3H, s, Me), 1.65 (3H, d, J = 7.5 Hz, Me) ppm. C NMR (75 MHz,
CDCl3): ! 171.5 (C=O), 137.4, 135.4, 133.3, 119.3 (arom C), 126.9, 126.4, 125.8, 123.7, 122.3, 108.5
(arom CH), 41.2 (C-3), 29.3 (Me), 24.3 (Me) ppm. MS m/z (rel intensity) 211 (M+, 100), 196 (50), 168
(80), 133 (50), 127 (30), 83 (25). FAB HRMS (acetone/NBA) calcd for C14H13NO 211.0997 (M). Found
211.0984.
Reduction of Indolinones 7 and 8. Acetylindolinone 7 or deacetylated indolinone 8 (0.2 mmol) was
dissolved in dry THF (4 mL) and cooled at 0 °C. LiAlH4 (0.4 mmol) was added and the mixture was
stirred at 0 °C for 1 h, then at room temperature for 4 h under an argon atmosphere. The reaction was
quenched by adding EtOAc (1 mL) and a saturated aqueous solution of Rochelle salt (2 mL). The
aqueous solution was filtered through a Celite column, washed with EtOAc, and the filtrate then
concentrated dryness. The residue was separated by silica gel TLC eluting with hexane-EtOAc (95:5 v/v),
giving the corresponding indole 10.
1,3-Dimethyl-1H-indole (10a).15,29 Yield 86%. Yellow liquid. IR (CHCl3): " 1616 (C=C) cm-1. 1H NMR
(500 MHz, CDCl3): ! 7.56 (1H, d, J = 8.5 Hz, arom H), 7.27 (1H, d, J = 8.5 Hz, arom H), 7.21 (1H, t, J =
7.3 Hz, arom H), 7.10 (1H, t, J = 7.3 Hz, arom H), 6.82 (1H, s, H-2), 3.73 (3H, s, Me), 2.32 (3H, s, Me)
13
ppm. C NMR (125 MHz, CDCl3): ! 136.9, 128.6, 110.1 (arom C), 126.5, 121.4, 118.9, 118.4, 109.0
(arom CH), 32.5 (Me), 9.5 (Me) ppm.
5-Fluoro-1,3-dimethyl-1H-indole (10b).30 Yield 69%. Yellow liquid. IR (CHCl3): " 1625 (C=C) cm-1.
1H NMR (500 MHz, CDCl3): ! 7.18 (1H, dd, J = 10.0, 2.5 Hz, arom H), 7.14 (1H, dd, J = 10.0, 4.0 Hz,
arom H), 6.94 (1H, dt, J = 10.0, 2.5 Hz, arom H), 6.83 (1H, s, H-2), 3.69 (3H, s, Me), 2.26 (3H, s, Me)
ppm. 13C NMR (125 MHz, CDCl3): ! 157.5 (d, J = 234.0 Hz), 133.6 (s), 128.8 (d, J = 9.7 Hz), 109.9 (d, J
= 4.8 Hz) (arom C), 128.2 (s), 109.7 (d, J = 15.6 Hz), 109.5 (s), 103.7 (d, J = 22.9 Hz) (arom CH), 32.7
(Me), 9.4 (Me) ppm.
5-Methoxy-1,3-dimethyl-1H-indole (10g).30 Yield 79%. IR (CHCl3): " 1620 (C=C) cm-1. 1H NMR (500
MHz, CDCl3): ! 7.07 (1H, d, J = 8.5 Hz, arom H), 6.92 (1H, d, J = 2.5 Hz, arom H), 6.79 (1H, dd, J = 8.5,
13
2.5 Hz, arom H), 6.70 (1H, s, arom H), 3.79 (3H, s, Me), 3.60 (3H, s, Me), 2.21 (3H, s, Me) ppm. C
NMR (125 MHz, CDCl3): ! 153.6, 132.4, 128.9, 109.4 (arom C), 127.2, 111.6, 109.7, 100.8 (arom CH),
55.9 (Me), 32.6 (Me), 9.5 (Me) ppm.

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ACKNOWLEDGEMENTS
This research was supported by a Grant-in-Aid for Scientific Research (C), No. 25410049, from the Japan
Society for the Promotion of Science, and also by the 2013-Core Research Program, “Integrated Science
for Molecular Chirality in Biology and Chemistry,” Graduate School of Science and Technology,
Kumamoto University, Japan. We gratefully acknowledge Nissan Chemical Industries, Ltd., for financial
support. HN thanks Mr. Shin-tarou Hashimoto and Mr. Shin-ji Tadano, Department of Science, Faculty
of Science, Kumamoto University, Japan, for their technical assistance.
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