I2-Mediated Cross-Dehydrogenative Coupling and Amidation of 3-Aryl Benzofuranones with Aryl Amines for the Synthesis of 3,3-Diaryl Indolin-2-ones

Article abstract of DOI:10.1021/acs.joc.0c02846

We have developed a protocol for efficient synthesis of indolin-2-ones from benzofuranones and aryl amines using iodine as a mediator. A diverse range of benzofuranones and aryl amines undergo cross-dehydrogenative coupling and amidation of 3-aryl benzofuranones for the cascade reaction to generate products in 24-93% yields. This reaction can be easily scaled-up to give an indolin-2-one in a gram scale. Further chemical manipulation of the products enabled useful transformations of the phenol ring including alkylation, arylation, etc.

Full text of DOI:10.1021/acs.joc.0c02846

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Article
I2‑Mediated Cross-Dehydrogenative Coupling and Amidation of
3‑Aryl Benzofuranones with Aryl Amines for the Synthesis of 3,3-
Diaryl Indolin-2-ones
Zhi Tang, Zhiqing Wang, Zhihong Peng,* Qinghua Yang, Shuang-Feng Yin, and Renhua Qiu*
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ABSTRACT: We have developed a protocol for efficient synthesis of
indolin-2-ones from benzofuranones and aryl amines using iodine as a
mediator. A diverse range of benzofuranones and aryl amines undergo
cross-dehydrogenative coupling and amidation of 3-aryl benzofur-
anones for the cascade reaction to generate products in 24−93%
yields. This reaction can be easily scaled-up to give an indolin-2-one in
a gram scale. Further chemical manipulation of the products enabled
useful transformations of the phenol ring including alkylation,
arylation, etc.
route is intramolecular Heck reaction of o-iodophenylacryla-
mides.10
INTRODUCTION
■
The indolin-2-one rings are a very important class of
compounds due to their existence in numerous natural
products, which display a wide range of physiological activities
(Figure 1).1 For example, oxyphenisatin (A) has been
Despite the great progress that has been made, the concise
and efficient synthesis of large sterically 3,3-diaryl indolin-2-
ones from easily available substrates under mild conditions still
remains a major challenge. There are only about ten papers
which can be divided into four routes. The first is acidic
activation of Isatin with an electrophilic substitution at
benzene which yielded 3,3-diaryl indolin-2-ones (Scheme
1a).11 The second is Friedel−Crafts alkylations to afford a
variety of 2-oxindoles with an all-carbon quaternary center
(Scheme 1b).12 Rearrangement reactions are also a good
strategy to obtain 3,3-diaryl indolin-2-ones (Scheme 1c).13
The last route is intramolecular or intermolecular cyclization
reaction (Scheme 1d).14 We are interested in the unique
capabilities and mechanistic features of benzofuranoness in C−
H functionalization.15 However, recently, much attention has
been focused toward the cross-dehydrogenative coupling
(CDC) reaction as an ideal, practical, and straightforward
strategy for carbon−carbon bond formation.16 Herein, we
disclose the first example for synthesizing 3,3-diaryl indolin-2-
ones from benzofuranones and aryl amines mediated by iodine
(Scheme 1e).
Figure 1. 3,3-Diaryl indolin-2-ones for medicines.
extensively used in humans as a laxative. TOP216 (B) is a
substituted derivative of oxyphenisatin, which was shown to be
a potent inhibitor of cell proliferation.2 Various indolin-2-ones
have been identified as pharmacologically active compounds in
extracts of the traditional anti-inflammatory herb. Furthermore,
it has been shown that they inhibit mast cell degranulation in
vitro (C).3,4
In order to fulfill the increasing demands of indolin-2-ones
in industries and biological research, a number of reactions
were developed, which are classified into several types of
transformations. The first and classical approach to synthesize
indolin-2-one relies on oxidation reactions of Boc-indoles in
the presence of oxidants.5 The reduction of indole-2,3-diones
with hydrazine is also a reliable approach to synthesize indolin-
2-ones.6 Transition-metal-catalyzed intramolecular amidation
reactions have emerged as another alternative method
providing structurally diverse indolin-2-ones.7−9 The fourth
Received: November 30, 2020
Published: January 25, 2021
https://dx.doi.org/10.1021/acs.joc.0c02846
© 2021 American Chemical Society
J. Org. Chem. 2021, 86, 2965−2973
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Article
a
Scheme 1. Synthesis of 3,3-Diaryl Indolin-2-ones
Table 1. Formation of 3a under Different Conditions
Entry
Oxidant
Solvent
Temp [°C] Isolated Yield [%]
1
2
3
4
5
6
7
8
I2
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
DMF
DMSO
toluene
THF
DMAC
1,4-dioxane
PhCN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
80
80
80
80
80
80
80
80
160
160
160
160
140
100
60
120
100
60
82
46
0
13
69
0
Ag2CO3
DTBP
TBHP
H2O2
m-CPBA
BPO
TBPB
I2
I2
I2
I2
I2
I2
I2
I2
I2
26
31
39
21
42
28
0
24
37
80
79
65
32
58
35
N.R.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
I2
I2
40
80
80
80
RESULTS AND DISCUSSION
I2 (50 mol%)
I2 (10 mol%)
−
■
First, the model reaction of 5-methyl-3-phenylbenzofuran-
2(3H)-one (1a) and naphthalen-2-amine (2a) was conducted
in CH3CN in the presence of I2 at 80 °C for 12 h (Table 1),
and the desired product 3a was obtained in 82% yield (entry
1).
a
Unless otherwise noted, all reactions were carried out with 1a (0.2
mmol), 2a (0.4 mmol), oxidant (1.0 equiv), and solvent (2.0 mL) in a
sealed tube for 12 h.
The starting material 1a was synthesized from phenols and
mandelic acids via our previous reported precedure.15a Various
oxidants could be used (entries 2−8), but I2 gave 3a in higher
yields. Among the solvents tested, CH3CN was found to be the
best solvent (entries 9−15). When the reaction was conducted
at higher temperatures, the yield did not increase, but when the
reaction was conducted at lower temperatures, the yield
decreased (entries 16−19). When the loading of I2 was
reduced to 0.5 equiv or 0.1 equiv, the yield of 3a sharply
decreased to 58% or 35%, respectively (entries 20−21). If the
reaction was conducted in the absence of I2, there is no
reaction; just starting materials would be recovered (entry 22).
Adopting the optimized reaction conditions, we investigated
the reactions of a variety of 3-arylbenzofuran-2(3H)-ones
(Scheme 2). We extended the substrate scope to 3-
arylbenzofuran-2(3H)-ones bearing methyl, ethyl, tert-butyl,
and phenyl substituents and obtained good yields (3a−3f).
The structure of 3a was confirmed by X-ray crystallography.17
The halide-substituted substrates can also react to form the
desired product 3g and 3h, which indicates high potential for
further transformation using traditional Suzuki−Miyaura cross-
coupling reactions. To our delight, the multisubstituted
substrate antioxidant HP-13618 gave 3i in 67% yield. Other
bromo- and chloro- substituents can also afford the target
products in good yields (3j−3n).
phenyl naphthylamine can be also easily transformed to the
indoline-2-ones 4c in 81% yield. Anilines with electron-
donating and electron-withdrawing substituents, including CN,
Me, Bn, AcNH, etc., reacted smoothly with benzofuranone to
afford the corresponding indolin-2-ones in good to high yields
(4d−4f, 4h), and N-methyl aniline gave 4g in 79% yield. Other
aniline derivatives having an electron-donating or a halide
group were also tolerant (4i−4o).
The present model reaction can be easily scaled-up. For
example, 1.42 g of 3a were synthesized in 78% yield from 1a
and 2a in the presence of 1.0 equiv of I2 in CH3CN at 80 °C
for 4 h (5.0 mmol) (Scheme 4). Aiming at the synthetic
application of the products, we performed further arylation and
alkylation transformation of 3a as demonstrated in Scheme 4.
Aromatic substitution of 3a with 1-fluoro-4-nitrobenzene
proceeded efficiently,19 to give diaryl ether 5 in 99% yield, in
the presence of cesium carbonate under mild conditions. The
classical alkylation of the OH group gave 6 in 93% yield.
To gain insights into the reaction mechanism, we conducted
several control experiments (Scheme 5). First, we added 2.0
equiv of a radical scavenger, such as TEMPO, which largely,
but not completely, suppressed the reaction (Scheme 5a).
Also, in the model reaction, we obtained the dimerization
product 7 of 1a in 8% yield (Scheme 5b). Furthermore, when
2a was reacted with 1.0 equiv of 7 under standard conditions,
3a was formed in 83% yield (Scheme 5c). A similar reaction of
7 with 2a in the presence of 1b afforded 3a and 3d in 82% and
56% yields, respectively (Scheme 5d).
Next, we applied the present method to a variety of
naphthylamines or anilines (Scheme 3). As for the hydroxyl
and bromo- groups attached to the naphthylamines, the target
products of indolin-2-ones 4a and 4b were produced in good
to excellent yields (47%, 88%), respectively. The secondary N-
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Scheme 2. Substrates Scope with Respect to Benzofuran-
2(3H)-ones
Scheme 3. Substrates Scope with Respect to
Naphthylamines or Anilines
a
a
a
a
Reaction conditions: 1 (0.2 mmol), 2a (0.4 mmol), I2 (1.0 equiv),
Reaction conditions: 1a (0.2 mmol), 2 (0.4 mmol), I2 (1.0 equiv),
CH3CN (2.0 mL), 80 °C, 12 h, in a sealed tube, isolated yield.
CH3CN (2.0 mL), 80 °C, 12 h, in a sealed tube, isolated yield.
a
Scheme 4. Gram Scale Synthesis and Applications
These results suggest that the present reaction involves a
radical process and that 7 would be a possible intermediate or
a resting state, as proposed in ref 20. However, when
benzofuranone without Ph group 8 reacted with 2a under
standard conditions, we cannot obtain the desired indolin-2-
one product but instead amidation product 9 in 83% yield,
indicating that the Ph group can stabilize the benzofuranone
radical (Scheme 5e). The structure of 9 was confirmed by X-
ray crystallography.17 When the loading of I2 was reduced to
10 mol % and 2 equiv of TBPB were added, the yield of 3a was
84%, indicating that iodine works as a catalyst and an oxidant
together (Scheme 5f).
Although the detailed reaction mechanism is still unclear, we
proposed a possible catalytic pathway in Scheme 6 according
to the above results and literature.12b,14a,21 The initial reaction
of iodine leads to the formation of an iodine radical under heat,
which can easily generate radical A and HI. Compound 7,
formed from radical A, can be a resting state of the present
reaction. Then radical A reacts with 2a and the iodine radical
to form the possible intermediate B. Intermediate B undergoes
ring-opening reaction to afford desired product 3a eventually.
a
Reaction conditions: (a) 3a (0.2 mmol), 1-fluoro-4-nitrobenzene
(0.4 mmol), Cs2CO3 (1.0 equiv), DMSO (1.0 mL), 40 °C, 4 h, in a
sealed tube, isolated yield. (b) 3a (0.2 mmol), 1-iodooctane (0.4
mmol), Cs2CO3 (1.0 equiv), DMSO (1.0 mL), 40 °C, 4 h, in a sealed
tube, isolated yield.
CONCLUSIONS
■
In summary, we developed an efficient and convenient method
for the synthesis of 3,3-diaryl indolin-2-ones via cross-
dehydrogenative coupling and amidation of 3-aryl benzofur-
anones form the cascade reaction of benzofuranones and aryl
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zero, AtlasS2 diffractometer. The crystal was kept at 100.01(19) K
during data collection.
Scheme 5. Control Experiments
General Procedure for Synthesis of Substrates. A 10 mL
oven-dried Schlenk tube equipped with a magnetic stirring bar,
benzofuran-2(3H)-ones 1 (0.20 mmol, 1.0 equiv), naphthylamines or
anilines 2 (0.4 mmol, 2.0 equiv), I2 (0.2 mmol, 1 equiv), and CH3CN
(2.0 mL) was vigorously stirred at 80 °C (oil bath) for 12 h. Then the
mixture was cooled to room temperature, and water (15 mL) was
added, followed by extraction with EtOAc (15 mL × 3). The
combined organic phases were dried over anhydrous Na2SO4, filtered,
and concentrated in vacuo. Further purification by flash column
chromatography on silica gel (eluting with petroleum ether/ethyl
acetate) provided the desired product 3 or 4.
1-(2-Hydroxy-5-methylphenyl)-1-phenyl-1,3-dihydro-2H-
benzo[e]indol-2-one (3a). The representative general procedure
mentioned above was followed. Purification by PTLC on silica gel
(petroleum ether/ethyl acetate = 5/1) afforded the title compound 3a
in 82% yield (59.9 mg) as a yellow solid; mp: 247−248 °C; Rf = 0.32
(petroleum ether/ethyl acetate = 5/1); 1H NMR (400 MHz, DMSO-
d6) δ 10.51 (s, 1H), 9.16 (s, 1H), 7.89 (t, J = 8.3 Hz, 2H), 7.30−7.20
(m, 9H), 6.95−6.83 (m, 2H), 6.52 (d, J = 8.0 Hz, 1H), 2.15 (s, 3H).
13C{1H} NMR (100 MHz, DMSO-d6) δ 181.3, 153.8, 141.3, 138.7,
131.4, 130.8, 123.0, 129.8, 129.7, 129.1, 128.9, 128.4, 127.9, 127.1,
127.0, 123.3, 123.0, 122.7, 116.0, 112.1, 61.1, 21.0. HRMS (EI) m/z:
[M + Na]+ calcd for C25H19NO2Na 388.1308, found 388.1297.
1-(5-Ethyl-2-hydroxyphenyl)-1-phenyl-1,3-dihydro-2H-
benzo[e]indol-2-one (3b). The representative general procedure
mentioned above was followed. Purification by PTLC on silica gel
(petroleum ether/ethyl acetate = 3/1) afforded the title compound 3b
in 51% yield (38.7 mg) as a yellow solid; mp: 200−202 °C; Rf = 0.42
(petroleum ether/ethyl acetate = 3/1); 1H NMR (400 MHz, DMSO-
d6) δ 10.53 (s, 1H), 9.18 (s, 1H), 7.89 (t, J = 8.9 Hz, 2H), 7.37−7.25
(m, 6H), 7.20 (dd, J = 16.9, 7.8 Hz, 3H), 6.91 (d, J = 11.1 Hz, 2H),
6.54 (d, J = 7.9 Hz, 1H), 2.43 (dd, J = 14.7, 7.3 Hz, 2H), 1.06 (t, J =
7.5 Hz, 3H). 13C{1H} NMR (100 MHz, DMSO-d6) δ 181.3, 154.0,
141.3, 138.8, 133.8, 130.7, 130.4, 130.0, 129.8, 129.8, 128.8, 128.4,
127.9, 127.9, 126.7, 123.2, 122.9, 122.7, 116.0, 112.1, 61.2, 28.1, 16.7.
HRMS (EI) m/z: [M + Na]+ calcd for C26H21NO2Na 402.1464,
found 402.1452.
Scheme 6. A Plausible Reaction Pathway
1-(2-Hydroxy-3,5-dimethylphenyl)-1-phenyl-1,3-dihydro-
2H-benzo[e]indol-2-one (3c). The representative general proce-
dure mentioned above was followed. Purification by PTLC on silica
gel (petroleum ether/ethyl acetate = 3/1) afforded the title
compound 3c in 93% yield (70.5 mg) as a yellow solid; mp: 83−84
amines in the presence of iodine under metal-free conditions.
The present reaction proceeds site selectively with respect to
both reactants to give 3,3-diaryl indolin-2-ones, which would
be candidates as potential synthetic pharmaceutical and
agrochemical ingredients. Preliminary mechanistic studies
indicate that this reaction involves a radical process. Phenol
ring groups in the products will allow useful further
transformations leading to functionalized indolin-2-ones.
1
°C; Rf = 0.45 (petroleum ether/ethyl acetate = 3/1); H NMR (400
MHz, DMSO-d6) δ 10.65 (s, 1H), 8.44 (s, 1H), 7.98−7.81 (m, 2H),
7.30 (dd, J = 8.6, 5.5 Hz, 6H), 7.25−7.14 (m, 3H), 6.83 (s, 1H), 6.64
(s, 1H), 2.09 (s, 3H), 2.02 (s, 3H).13C{1H} NMR (100 MHz,
DMSO-d6) δ 181.9, 152.0, 140.9, 139.0, 131.1, 130.8, 130.1, 129.9,
129.8, 129.2, 128.4, 127.8, 127.6, 127.0, 125.3, 123.9, 123.1, 122.8,
112.2, 61.8, 21.0, 17.0. HRMS (EI) m/z: [M + H]+ calcd for
C26H22NO2 380.1645, found 380.1631.
EXPERIMENTAL SECTION
■
General Information. All commercially available reagents were
used without further purification. The starting material 1 series was
synthesized from phenols and mandelic acids via our previous
reported precedure.15a The 2 series and 8 were purchased from
Energy. The dehydrated solvents were purchased and redistilled
before use. Nuclear magnetic resonance (NMR) spectra were
acquired at 298 K on a 400 MHz Bruker NMR spectrometer with
the sample dissolved in DMSO-d6 or CDCl3 (unless stated
otherwise). All values of chemical shift were reported in parts per
million (ppm) relative to the solvent signal with the coupling constant
(J) reported in hertz. All compounds were characterized by 1H NMR,
13C NMR, and EI (or HRMS (double focusing mass analyzer)).
HRMS data were collected on a Bruker solanX 70 FT-MS and Agilent
6224 TOF mass spectrometer. For substrates and products that
contained F, selected ones were also characterized by 19F NMR.
Column chromatography was performed on silica gel (300−400
mesh) using petroleum ether (PE)/ethyl acetate (EA) as developing
solvent. The crystal measurement utilized a SuperNova, Dual, Cu at
1-(2-Hydroxy-4,6-dimethylphenyl)-1-phenyl-1,3-dihydro-
2H-benzo[e]indol-2-one (3d). The representative general proce-
dure mentioned above was followed. Purification by PTLC on silica
gel (petroleum ether/ethyl acetate = 1/1) afforded the title
compound 3d in 77% yield (58.4 mg) as a yellow solid; mp: 212−
1
213 °C; Rf = 0.40 (petroleum ether/ethyl acetate = 1/1); H NMR
(400 MHz, DMSO-d6) δ 10.33 (s, 1H), 9.32 (s, 1H), 8.11−7.78 (m,
3H), 7.31 (d, J = 48.6 Hz, 6H), 7.03 (s, 1H), 6.42 (dd, J = 41.9, 25.5
Hz, 3H), 2.11 (s, 3H), 1.70 (s, 3H).13C{1H} NMR (100 MHz,
DMSO-d6) δ 182.3, 156.5, 141.2, 141.11, 139.1, 138.4, 137.0, 131.8,
131.0, 130.1, 129.9, 129.4, 128.4, 127.8, 127.4, 127.2, 125.1, 124.2,
122.8, 122.3, 114.8, 112.1, 61.3, 23.3, 20.8. HRMS (EI) m/z: [M +
Na]+ calcd for C26H21NO2Na 402.1464, found 402.1452.
1-(3-(tert-Butyl)-2-hydroxyphenyl)-1-phenyl-1,3-dihydro-
2H-benzo[e]indol-2-one (3e). The representative general proce-
dure mentioned above was followed. Purification by PTLC on silica
gel (petroleum ether/ethyl acetate = 3/1) afforded the title
compound 3e in 56% yield (45.6 mg) as a yellow solid; mp: 299−
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1
300 °C; Rf = 0.35 (petroleum ether/ethyl acetate = 3/1); H NMR
(400 MHz, DMSO-d6) δ 10.55 (s, 1H), 9.21 (s, 1H), 7.89 (dd, J =
11.4, 8.7 Hz, 2H), 7.40−7.25 (m, 6H), 7.24−7.15 (m, 5H), 6.56 (d, J
= 8.3 Hz, 1H), 1.15 (s, 9H).13C{1H} NMR (100 MHz, DMSO-d6) δ
181.3, 153.8, 141.3, 140.6, 138.9, 130.6, 130.0, 129.8, 129.8, 128.6,
128.3, 128.2, 127.9, 126.7, 125.0, 123.1, 122.9, 122.6, 115.5, 112.1,
61.4, 34.1, 31.7. HRMS (EI) m/z: [M + H]+ calcd for C28H26NO2
408.1958, found 408.1948.
= 7.6 Hz, 1H), 6.75 (t, J = 7.6 Hz, 1H), 2.05 (s, 3H). 13C{1H} NMR
(100 MHz, DMSO-d6) δ 181.0, 153.7, 140.7, 138.2, 131.1, 130.3,
130.2, 129.8, 129.5, 128.4, 126.8, 125.2, 122.8, 122.7, 122.1, 121.0,
119.1, 111.91, 61.0, 16.7. HRMS (EI) m/z: [M]+ calcd for
C25H18BrNO2 443.051, found 443.052.
1-(4-Bromophenyl)-1-(2-hydroxy-3,5-dimethylphenyl)-1H-
benzo[e]indol-2(3H)-one (3k). The representative general proce-
dure mentioned above was followed. Purification by PTLC on silica
gel (petroleum ether/ethyl acetate = 5/1) afforded the title
compound 3k in 53% yield (48.4 mg) as a white solid; mp: 209−
1-(4-Hydroxy-[1,1′-biphenyl]-3-yl)-1-phenyl-1,3-dihydro-
2H-benzo[e]indol-2-one (3f). The representative general proce-
dure mentioned above was followed. Purification by PTLC on silica
gel (petroleum ether/ethyl acetate = 3/1) afforded the title
compound 3f in 53% yield (45.3 mg) as a yellow solid; mp: 240−
1
210 °C; Rf = 0.33 (petroleum ether/ethyl acetate = 5/1); H NMR
(400 MHz, CDCl3) δ 10.50 (s, 1H), 9.25 (s, 1H), 7.83−7.74 (m,
2H), 7.35−7.26 (m, 4H), 7.25−7.16 (m, 2H), 7.10 (d, J = 5.0 Hz,
2H), 6.95 (s, 1H), 6.46 (s, 1H), 2.25 (s, 3H), 1.95 (s, 3H). 13C{1H}
NMR (100 MHz, CDCl3) δ 185.2, 152.7, 137.4, 136.5, 132.5, 131.7,
131.1, 131.0, 130.2, 130.0, 129.5, 129.2, 129.1, 128.3, 127.4, 125.8,
124.2, 123.3, 122.0, 121.8, 111.8, 63.9, 20.6, 16.6. HRMS (EI) m/z:
[M]+ calcd for C26H20BrNO2 457.0666, found 457.0677.
1
241 °C; Rf = 0.32 (petroleum ether/ethyl acetate = 3/1); H NMR
(400 MHz, DMSO-d6) δ 10.61 (s, 1H), 9.66 (s, 1H), 7.96−7.85 (m,
2H), 7.40 (t, J = 7.3 Hz, 6H), 7.32 (t, J = 9.5 Hz, 6H), 7.29−7.12 (m,
4H), 6.74 (d, J = 8.3 Hz, 1H).13C{1H} NMR (100 MHz, DMSO-d6)
δ 181.1, 155.9, 141.5, 140.9, 138.5, 131.0, 130.7, 130.1, 129.9, 129.7,
129.5, 129.4, 128.6, 128.1, 127.3, 127.1, 127.0, 126.4, 123.0, 122.9,
122.5, 116.7, 112.2, 61.2. HRMS (EI) m/z: [M + Na]+ calcd for
C30H21NO2Na 450.1464, found 450.1454.
1-(4-Chlorophenyl)-1-(2-hydroxy-3,5-dimethylphenyl)-1H-
benzo[e]indol-2(3H)-one (3l). The representative general proce-
dure mentioned above was followed. Purification by PTLC on silica
gel (petroleum ether/ethyl acetate = 5/1) afforded the title
compound 3l in 83% yield (68 mg) as a white solid; mp: 230−231
1-(5-Chloro-2-hydroxyphenyl)-1-phenyl-1,3-dihydro-2H-
benzo[e]indol-2-one (3g). The representative general procedure
mentioned above was followed. Purification by PTLC on silica gel
(petroleum ether/ethyl acetate = 3/1) afforded the title compound 3g
in 77% yield (59.3 mg) as a yellow solid; mp: 224−225 °C; Rf = 0.38
(petroleum ether/ethyl acetate = 3/1); 1H NMR (400 MHz, DMSO-
d6) δ 10.62 (s, 1H), 9.78 (s, 1H), 7.91 (dd, J = 13.2, 5.4 Hz, 2H),
7.40−7.28 (m, 10H), 7.16 (dd, J = 8.6, 2.2 Hz, 1H), 6.97 (d, J = 2.1
Hz, 1H), 6.64 (d, J = 8.6 Hz, 1H).13C{1H} NMR (100 MHz, DMSO-
d6) δ 180.5, 155.1, 141.6, 137.9, 131.5, 130.6, 130.4, 130.1, 130.0,
130.0, 129.7, 129.7, 128.8, 128.6, 128.3, 127.3, 123.1, 122.4, 122.2,
117.7, 112.2, 60.8.HRMS (EI) m/z: [M + Na]+ calcd for
C24H16ClNO2Na 408.0762, found 408.0758.
1
°C; Rf = 0.35 (petroleum ether/ethyl acetate = 5/1); H NMR (400
MHz, CDCl3) δ 9.72 (s, 1H), 8.77 (s, 1H), 7.85−7.77 (m, 2H), 7.33
(d, J = 8.3 Hz, 1H), 7.31−7.26 (m, 1H), 7.22 (d, J = 8.1 Hz, 3H),
7.18 (s, 3H), 6.97 (s, 1H), 6.46 (s, 1H), 2.25 (s, 3H), 1.98 (s, 3H).
13C{1H} NMR (100 MHz, CDCl3) δ 185.4, 152.6, 137.5, 135.9,
133.5, 132.4, 131.0, 130.9, 130.2, 129.7, 129.5, 129.2, 129.1, 128.7,
128.2, 127.3, 125.8, 124.2, 123.3, 111.8, 63.9, 20.6, 16.6. HRMS (EI)
m/z: [M]+ calcd for C26H20ClNO2 413.1179, found 413.1183.
1-(4-Chlorophenyl)-1-(2-hydroxy-5-methylphenyl)-1H-
benzo[e]indol-2(3H)-one (3m). The representative general proce-
dure mentioned above was followed. Purification by PTLC on silica
gel (petroleum ether/ethyl acetate = 5/1) afforded the title
compound 3m in 51% yield (40.3 mg) as a yellow solid; mp: 181−
1-(4-Bromophenyl)-1-(2-hydroxy-5-methylphenyl)-1,3-di-
hydro-2H-benzo[e]indol-2-one (3h). The representative general
procedure mentioned above was followed. Purification by PTLC on
silica gel (petroleum ether/ethyl acetate = 3/1) afforded the title
compound 3h in 63% yield (55.8 mg) as a yellow solid; mp: 112−113
1
182 °C; Rf = 0.43 (petroleum ether/ethyl acetate = 5/1); H NMR
(400 MHz, CDCl3) δ 9.94 (s, 1H), 9.19 (s, 1H), 7.87−7.78 (m, 2H),
7.34−7.16 (m, 8H), 7.04 (d, J = 7.8 Hz, 1H), 6.93 (d, J = 8.1 Hz,
1H), 6.65 (s, 1H), 2.02 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3) δ
185.0, 154.4, 137.5, 135.8, 133.6, 131.4, 131.0, 131.0, 130.9, 130.2,
129.9, 129.7, 129.5, 128.8, 127.5, 125.4, 124.2, 123.2, 119.6, 111.8,
63.7, 20.7. HRMS (EI) m/z: [M]+ calcd for C25H18ClNO2 399.1019,
found 399.1026.
1
°C; Rf = 0.30 (petroleum ether/ethyl acetate = 3/1); H NMR (400
MHz, DMSO-d6) δ 10.60 (s, 1H), 9.21 (s, 1H), 7.95−7.84 (m, 2H),
7.53 (d, J = 6.0 Hz, 2H), 7.29−7.21 (m, 6H), 6.94−6.84 (m, 2H),
6.53 (d, J = 7.9 Hz, 1H), 2.17 (s, 3H). 13C{1H} NMR (100 MHz,
DMSO-d6) δ 180.9, 153.7, 141.4, 138.3, 131.5, 131.2, 130.6, 130.1,
123.0, 129.9, 129.3, 128.5, 127.3, 127.2, 123.1, 122.7, 122.5, 121.5,
116.1, 112.2, 60.8, 21.0. HRMS (EI) m/z: [M + H]+ calcd for
C25H19NO2Br 444.0594, found 444.0582.
1-(4-Bromophenyl)-1-(2-hydroxy-4,6-dimethylphenyl)-1H-
benzo[e]indol-2(3H)-one (3n). The representative general proce-
dure mentioned above was followed. Purification by PTLC on silica
gel (petroleum ether/ethyl acetate = 3/1) afforded the title
compound 3n in 25% yield (23 mg) as a yellow solid; mp: 219−
1-(3,5-Di-tert-butyl-2-hydroxyphenyl)-1-(3,4-dimethylphen-
yl)-1,3-dihydro-2H-benzo[e]indol-2-one (3i). The representative
general procedure mentioned above was followed. Purification by
PTLC on silica gel (petroleum ether/ethyl acetate = 5/1) afforded the
title compound 3f in 67% yield (65.8 mg) as a yellow solid; mp: 146−
1
220 °C; Rf = 0.32 (petroleum ether/ethyl acetate = 3/1); H NMR
(400 MHz, CDCl3) δ 9.27 (s, 1H), 8.91 (s, 1H), 8.08 (s, 1H), 7.75
(d, J = 6.7 Hz, 1H), 7.55 (s, 2H), 7.32 (s, 2H), 7.07 (d, J = 6.6 Hz,
1H), 6.94 (s, 1H), 6.73 (s, 1H), 6.52 (s, 1H), 6.31 (d, J = 5.8 Hz,
1H), 6.15 (s, 1H), 2.06 (s, 3H), 1.85 (s, 3H). 13C{1H} NMR (100
MHz, CDCl3) δ 186.6, 155.0, 139.1, 138.8, 138.4, 133.4, 131.5, 131.3,
130.5, 130.4, 129.6, 129.4, 127.1, 126.3, 123.5, 123.3, 123.1, 122.4,
122.2, 114.9, 112.0, 62.1, 23.5, 20.8. HRMS (EI) m/z: [M]+ calcd for
C26H20BrNO2 457.0677, found 457.0674.
1-(2-Hydroxy-5-isopropylphenyl)-1-phenyl-1H-benzo[e]-
indol-2(3H)-one (3o). The representative general procedure
mentioned above was followed. Purification by PTLC on silica gel
(petroleum ether/ethyl acetate = 5/1) afforded the title compound 3o
in 81% yield (63.2 mg) as a yellow solid; mp: 202−203 °C; Rf = 0.35
(petroleum ether/ethyl acetate = 5/1); 1H NMR (400 MHz, DMSO-
d6) δ 10.58 (s, 1H), 9.25 (s, 1H), 7.95−7.88 (m, 2H), 7.32 (d, J = 8.3
Hz, 6H), 7.26−7.13 (m, 3H), 6.98 (s, 2H), 6.58 (d, J = 8.6 Hz, 1H),
2.78−2.68 (m, 1H), 1.15−1.08 (m, 6H). 13C{1H} NMR (100 MHz,
DMSO-d6) δ 180.9, 153.7, 140.9, 138.5, 138.0, 130.3, 129.6, 129.4,
129.4, 128.8, 128.2, 128.0, 127.5, 126.4, 125.8, 122.8, 122.5, 122.2,
1
147 °C; Rf = 0.51 (petroleum ether/ethyl acetate = 5/1); H NMR
(400 MHz, DMSO-d6) δ 11.60 (s, 1H), 10.06 (s, 1H), 8.00 (d, J = 8.6
Hz, 1H), 7.90 (d, J = 8.1 Hz, 1H), 7.45 (d, J = 8.6 Hz, 1H), 7.25 (d, J
= 8.0 Hz, 2H), 7.20 (d, J = 3.8 Hz, 2H), 6.99 (d, J = 8.0 Hz, 1H), 6.85
(s, 2H), 6.54 (d, J = 1.8 Hz, 1H), 2.10 (s, 3H), 2.05 (s, 3H), 1.42 (s,
9H), 0.84 (s, 9H).13C{1H} NMR (100 MHz, DMSO-d6) δ 185.4,
154.2, 140.6, 138.8, 138.1, 136.3, 135.6, 135.4, 131.0, 130.7, 130.0,
129.8, 129.7, 128.7, 127.1, 126.7, 126.0, 125.4, 124.0, 123.8, 123.6,
122.1, 112.8, 64.7, 35.4, 34.1, 31.4, 30.1, 20.0, 19.4. HRMS (EI) m/z:
[M + Na]+ calcd for C34H37NO2Na514.2716, found 514.2697.
1-(4-Bromophenyl)-1-(2-hydroxy-3-methylphenyl)-1H-
benzo[e]indol-2(3H)-one (3j). The representative general proce-
dure mentioned above was followed. Purification by PTLC on silica
gel (petroleum ether/ethyl acetate = 3/1) afforded the title
compound 3j in 24% yield (21 mg) as a green solid; mp: 101−102
1
°C; Rf = 0.32 (petroleum ether/ethyl acetate = 5/1); H NMR (400
MHz, DMSO-d6) δ 10.74 (s, 1H), 8.70 (s, 1H), 7.96−7.87 (m, 2H),
7.51 (s, 2H), 7.38−7.15 (m, 6H), 7.02 (d, J = 7.2 Hz, 1H), 6.85 (d, J
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115.5, 111.7, 60.9, 40.2, 40.0, 24.3, 24.2. HRMS (EI) m/z: [M]+ calcd
for C27H23NO2 393.1726, found 393.1729.
5-Benzoyl-3-(2-hydroxy-5-methylphenyl)-3-phenylindolin-
2-one (4f). The representative general procedure mentioned above
was followed. Purification by PTLC on silica gel (petroleum ether/
ethyl acetate = 3/1) afforded the title compound 4f in 74% yield (62.0
mg) as a yellow solid; mp: 232−233 °C; Rf = 0.40 (petroleum ether/
4-Hydroxy-1-(2-hydroxy-5-methylphenyl)-1-phenyl-1,3-di-
hydro-2H-benzo[e]indol-2-one (4a). The representative general
procedure mentioned above was followed. Purification by PTLC on
silica gel (petroleum ether/ethyl acetate = 2/1) afforded the title
compound 4a in 47% yield (35.8 mg) as a green solid; mp: 276−277
1
ethyl acetate = 3/1); H NMR (400 MHz, CDCl3) δ 9.09 (s, 1H),
8.36 (s, 1H), 7.80 (dd, J = 8.2, 1.2 Hz, 1H), 7.71 (d, J = 7.4 Hz, 2H),
7.65 (s, 1H), 7.59 (t, J = 7.4 Hz, 1H), 7.46 (t, J = 7.6 Hz, 2H), 7.30 (t,
J = 6.6 Hz, 3H), 7.24−7.15 (m, 2H), 7.14−7.04 (m, 2H), 6.90 (d, J =
8.1 Hz, 1H), 6.83 (s, 1H), 2.24 (s, 3H). 13C{1H} NMR (100 MHz,
CDCl3) δ 195.5, 183.3, 153.8, 143.5, 139.3, 137.7, 133.0, 132.7, 132.3,
132.0, 130.7, 129.8, 129.6, 129.6, 129.2, 129.0, 128.3, 127.9, 126.7,
124.7, 119.6, 110.5, 62.3, 20.7. HRMS (EI) m/z: [M + H]+ calcd for
C28H22NO3 420.1584, found 420.1583.
3-(2-Hydroxy-5-methylphenyl)-1-methyl-3-phenylindolin-
2-one (4g). The representative general procedure mentioned above
was followed. Purification by PTLC on silica gel (petroleum ether/
ethyl acetate = 3/1) afforded the title compound 4g in 79% yield
(52.0 mg) as a yellow solid; mp: 153−154 °C; Rf = 0.45 (petroleum
ether/ethyl acetate = 3/1); 1H NMR (400 MHz, CDCl3) δ 7.35−7.25
(m, 5H), 7.13−7.01 (m, 5H), 6.54 (d, J = 8.6 Hz, 2H), 3.79 (s, 1H),
2.81 (s, 3H), 2.33 (s, 3H).13C{1H} NMR (100 MHz, CDCl3) δ 177.8,
150.5, 148.8, 141.5, 134.0, 131.7, 129.4, 129.2, 128.7, 128.6, 128.1,
127.6, 126.4, 112.3, 110.6, 60.8, 30.6, 21.2.HRMS (EI) m/z: [M +
Na]+ calcd for C22H19NO2Na 352.1308, found 352.1320.
N-(3-(2-Hydroxy-5-methylphenyl)-2-oxo-3-phenylindolin-5-
yl)acetamide (4h). The representative general procedure mentioned
above was followed. Purification by PTLC on silica gel (petroleum
ether/ethyl acetate = 1/1) afforded the title compound 4g in 64%
yield (47.6 mg) as a white solid; mp: 148−149 °C; Rf = 0.35
(petroleum ether/ethyl acetate = 1/1); 1H NMR (400 MHz, DMSO-
d6) δ 10.31 (s, 1H), 9.77 (s, 1H), 9.29 (s, 1H), 7.50 (d, J = 8.3 Hz,
1H), 7.33−7.25 (m, 6H), 6.90 (d, J = 8.1 Hz, 1H), 6.82 (d, J = 8.3
Hz, 1H), 6.62 (d, J = 8.0 Hz, 1H), 6.50 (s, 1H), 2.09 (s, 3H), 1.96 (s,
3H). 13C{1H} NMR (100 MHz, DMSO-d6) δ 179.9, 168.2, 153.5,
139.8, 138.4, 133.8, 133.5, 130.5, 129.3, 129.1, 128.8, 128.5, 127.7,
127.2, 119.3, 117.9, 116.1, 109.5, 60.5, 40.5, 40.3, 40.1, 39.9, 39.7,
39.5, 39.3, 24.2, 20.9. HRMS (EI) m/z: [M + Na]+ calcd for
C23H20N2O3Na 395.1366, found 395.1361.
5-Ethoxy-3-(2-hydroxy-5-methylphenyl)-3-phenylindolin-2-
one (4i). The representative general procedure mentioned above was
followed. Purification by PTLC on silica gel (petroleum ether/ethyl
acetate = 5/1) afforded the title compound 4i in 48% yield (34 mg) as
a yellow solid; mp: 166−167 °C; Rf = 0.35 (petroleum ether/ethyl
acetate = 5/1); 1H NMR (400 MHz, DMSO-d6) δ 10.27 (s, 1H), 9.27
(s, 1H), 7.31−7.25 (m, 5H), 6.89 (d, J = 8.1 Hz, 1H), 6.78 (s, 1H),
6.72 (s, 1H), 6.64−6.55 (m, 2H), 3.89 (q, J = 6.9 Hz, 2H), 2.09 (s,
3H), 1.25 (t, J = 6.9 Hz, 3H). 13C{1H} NMR (100 MHz, DMSO-d6)
δ 179.6, 154.2, 153.5, 140.3, 136.1, 134.8, 130.5, 129.1, 129.0, 128.6,
128.4, 127.4, 127.3, 116.3, 114.0, 113.2, 110.0, 63.9, 61.0, 20.8, 15.2.
HRMS (EI) m/z: [M]+ calcd for C23H21NO3 359.1518, found
359.1521.
1
°C; Rf = 0.50 (petroleum ether/ethyl acetate = 2/1); H NMR (400
MHz, DMSO-d6) δ 10.37 (s, 1H), 10.13 (s, 1H), 9.14 (s, 1H), 7.67
(d, J = 8.1 Hz, 1H), 7.30 (s, 4H), 7.24−7.07 (m, 4H), 6.97 (t, J = 7.4
Hz, 1H), 6.88 (d, J = 7.9 Hz, 1H), 6.83 (s, 1H), 6.51 (d, J = 7.9 Hz,
1H), 2.14 (s, 3H). 13C{1H} NMR (100 MHz, DMSO-d6) δ 181.1,
153.8, 143.0, 138.8, 133.3, 131.4, 131.1, 129.1, 128.8, 128.4, 127.8,
127.0, 125.6, 124.5, 123.6, 123.2, 122.6, 116.0, 110.4, 61.7, 21.0.
HRMS (EI) m/z: [M + Na]+ calcd for C25H19NO3Na404.1257, found
404.1246.
7-Bromo-1-(2-hydroxy-5-methylphenyl)-1-phenyl-1,3-dihy-
dro-2H-benzo[e]indol-2-one (4b). The representative general
procedure mentioned above was followed. Purification by PTLC on
silica gel (petroleum ether/ethyl acetate = 3/1) afforded the title
compound 4b in 88% yield (78.0 mg) as a yellow solid; mp: 177−178
1
°C; Rf = 0.25 (petroleum ether/ethyl acetate = 3/1); H NMR (400
MHz, DMSO-d6) δ 10.64 (s, 1H), 9.24 (s, 1H), 8.20 (s, 1H), 7.93 (d,
J = 8.5 Hz, 1H), 7.49−7.17 (m, 8H), 6.92 (d, J = 7.9 Hz, 1H), 6.86 (s,
1H), 6.54 (d, J = 7.9 Hz, 1H), 2.17 (s, 3H).13C{1H} NMR (100 MHz,
DMSO-d6) δ 181.1, 153.7, 142.0, 138.4, 131.5, 131.2, 129.9, 129.3,
129.2, 129.1, 128.7, 128.6, 128.0, 127.2, 124.8, 123.6, 116.0, 115.8,
113.2, 61.0, 21.0. HRMS (EI) m/z: [M + Na]+ calcd for
C25H18NO2BrNa 466.0413, found 466.0412.
1-(2-Hydroxy-5-methylphenyl)-1,3-diphenyl-1,3-dihydro-
2H-benzo[e]indol-2-one (4c). The representative general proce-
dure mentioned above was followed. Purification by PTLC on silica
gel (petroleum ether/ethyl acetate = 5/1) afforded the title
compound 4c in 81% yield (71.4 mg) as a yellow solid; mp: 289−
1
290 °C; Rf = 0.30 (petroleum ether/ethyl acetate = 5/1); H NMR
(400 MHz, CDCl3) δ 9.06 (s, 1H), 7.88 (dd, J = 18.6, 8.4 Hz, 2H),
7.63−7.48 (m, 6H), 7.37−7.22 (m, 8H), 7.13 (d, J = 8.8 Hz, 1H),
7.04 (d, J = 8.1 Hz, 1H), 6.72 (s, 1H), 2.07 (s, 3H).13C{1H} NMR
(100 MHz, CDCl3) δ 182.4, 155.1, 140.2, 137.6, 133.8, 131.4, 131.3,
130.7, 130.5, 130.2, 129.8, 129.3, 129.3, 128.8, 128.5, 128.0, 127.7,
127.3, 126.9, 125.6, 124.3, 123.9, 122.3, 119.8, 111.0, 63.8, 20.6.
HRMS (EI) m/z: [M + H]+ calcd for C31H24NO2 442.1802, found
442.1792.
3-(2-Hydroxy-5-methylphenyl)-5,7-dimethyl-3-phenylindo-
lin-2-one (4d). The representative general procedure mentioned
above was followed. Purification by PTLC on silica gel (petroleum
ether/ethyl acetate = 3/1) afforded the title compound 4d in 78%
yield (53.5 mg) as a yellow solid; mp: 91−92 °C; Rf = 0.40
(petroleum ether/ethyl acetate = 3/1); 1H NMR (400 MHz, CDCl3)
δ 10.15 (s, 1H), 9.03 (s, 1H), 7.29 (d, J = 7.6 Hz, 3H), 7.18 (d, J = 7.2
Hz, 2H), 7.09 (d, J = 8.1 Hz, 1H), 6.96−6.90 (m, 2H), 6.86 (s, 1H),
6.74 (s, 1H), 2.28 (s, 6H), 2.23 (s, 3H). 13C{1H} NMR (100 MHz,
CDCl3) δ 184.3, 154.6, 140.4, 135.7, 133.0, 132.7, 130.6, 130.6, 129.8,
129.2, 128.8, 127.4, 126.5, 125.1, 125.0, 120.6, 119.9, 63.6, 21.3, 20.8,
16.4. HRMS (EI) m/z: [M + Na]+ calcd for C23H21NO2Na 366.1464,
found 366.1478.
3-(2-Hydroxy-5-methylphenyl)-2-oxo-3-phenylindoline-5-
carbonitrile (4e). The representative general procedure mentioned
above was followed. Purification by PTLC on silica gel (petroleum
ether/ethyl acetate = 3/1) afforded the title compound 4e in 30%
yield (20.4 mg) as a white solid; mp: 253−254 °C; Rf = 0.30
(petroleum ether/ethyl acetate = 3/1); 1H NMR (400 MHz, DMSO-
d6) δ 10.90 (s, 1H), 9.39 (s, 1H), 7.70 (d, J = 8.1 Hz, 1H), 7.50 (s,
1H), 7.40−7.27 (m, 5H), 7.03 (d, J = 8.1 Hz, 1H), 6.92 (d, J = 8.0
Hz, 1H), 6.61 (d, J = 8.1 Hz, 1H), 6.51 (s, 1H), 2.09 (s, 3H).
13C{1H} NMR (100 MHz, DMSO-d6) δ 179.6, 153.2, 147.4, 138.4,
3-(2-Hydroxy-5-methylphenyl)-5-methyl-3-phenylindolin-
2-one (4j). The representative general procedure mentioned above
was followed. Purification by PTLC on silica gel (petroleum ether/
ethyl acetate = 5/1) afforded the title compound 4j in 45% yield (29.6
mg) as a yellow solid; mp: 103−104 °C; Rf = 0.32 (petroleum ether/
1
ethyl acetate = 5/1); H NMR (400 MHz, CDCl3) δ 9.48 (s, 1H),
8.95 (s, 1H), 7.27−7.23 (m, 3H), 7.16 (d, J = 6.8 Hz, 2H), 7.08−6.99
(m, 2H), 6.93−6.83 (m, 3H), 6.80 (s, 1H), 2.28 (s, 3H), 2.19 (s, 3H).
13C{1H} NMR (100 MHz, CDCl3) δ 183.7, 154.3, 140.3, 137.0,
133.0, 130.5, 129.8, 129.3, 129.0, 128.9, 127.7, 127.5, 126.6, 125.2,
119.8, 111.0, 63.0, 21.4, 20.8. HRMS (EI) m/z: [M]+ calcd for
C22H19NO2 329.1408, found 329.1416.
3-(2-Hydroxy-5-methylphenyl)-5-methoxy-3-phenylindo-
lin-2-one (4k). The representative general procedure mentioned
above was followed. Purification by PTLC on silica gel (petroleum
ether/ethyl acetate = 5/1) afforded the title compound 4k in 84%
yield (57.5 mg) as a yellow solid; mp: 175−176 °C; Rf = 0.42
(petroleum ether/ethyl acetate = 5/1); 1H NMR (400 MHz, DMSO-
134.6, 133.8, 130.7, 129.5, 129.1, 128.8, 128.8, 128.4, 128.0, 127.5,
119.9, 115.9, 110.5, 103.6, 59.8, 20.8. HRMS (EI) m/z: [M + H]+
calcd for C22H17N2O2 341.1284, found 341.1279.
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d6) δ 10.32 (s, 1H), 9.30 (s, 1H), 8.35 (s, 1H), 7.37−7.28 (m, 5H),
6.93 (d, J = 8.1 Hz, 1H), 6.87−6.80 (m, 2H), 6.77 (s, 1H), 6.67−6.61
(m, 2H), 3.68 (s, 3H), 2.12 (s, 3H). 13C{1H} NMR (100 MHz,
DMSO-d6) δ 179.3, 154.6, 153.1, 139.8, 135.8, 134.4, 130.2, 128.8,
128.6, 128.2, 128.1, 127.1, 126.9, 115.9, 113.0, 112.2, 109.7, 60.6,
55.5, 20.5. HRMS (EI) m/z: [M]+ calcd for C22H19NO3 345.1356,
found 345.1365.
= 8.6 Hz, 1H), 7.37 (s, 4H), 7.32−7.14 (m, 6H), 6.95 (d, J = 8.5 Hz,
1H), 6.89 (d, J = 8.0 Hz, 1H), 6.33 (d, J = 9.1 Hz, 2H), 2.33 (s, 3H).
13C{1H} NMR (100 MHz, DMSO-d6) δ 180.2, 162.0, 150.2, 142.0,
141.0, 137.5, 135.4, 135.1, 132.4, 130.5, 130.3, 130.1, 130.1, 129.8,
128.7, 128.4, 127.5, 125.3, 123.2, 122.3, 122.0, 122.0, 115.7, 112.1,
60.6, 21.3. HRMS (ESI) m/z: [M + Na]+ calcd for C31H22N2O4Na
509.1472, found 509.1470.
3-(2-Hydroxy-5-methylphenyl)-5-iodo-3-phenylindolin-2-
one (4l). The representative general procedure mentioned above was
followed. Purification by PTLC on silica gel (petroleum ether/ethyl
acetate = 5/1) afforded the title compound 4l in 24% yield (21 mg) as
a yellow solid; mp: 141−142 °C; Rf = 0.33 (petroleum ether/ethyl
acetate = 3/1); 1H NMR (400 MHz, CDCl3) δ 9.01 (s, 1H), 8.38 (s,
1H), 7.54 (d, J = 8.2 Hz, 1H), 7.36 (s, 1H), 7.30 (d, J = 6.5 Hz, 3H),
7.17−7.13 (m, 2H), 7.09−7.03 (m, 1H), 6.86 (d, J = 8.1 Hz, 1H),
6.74 (d, J = 8.7 Hz, 2H), 2.22 (s, 3H). 13C{1H} NMR (100 MHz,
CDCl3) δ 182.6, 153.8, 139.3, 137.5, 135.7, 135.2, 130.8, 129.7, 129.6,
129.1, 128.0, 126.8, 124.9, 119.7, 113.0, 86.1, 62.5, 20.8. HRMS (EI)
m/z: [M]+ calcd for C21H16INO2 441.0219, found 441.0226.
5-Chloro-3-(2-hydroxy-5-methylphenyl)-3-phenylindolin-2-
one (4m). The representative general procedure mentioned above
was followed. Purification by PTLC on silica gel (petroleum ether/
ethyl acetate = 5/1) afforded the title compound 4n in 83.0% yield
(58 mg) as a white solid; mp: 144−145 °C; Rf = 0.35 (petroleum
1-(5-Methyl-2-(octyloxy)phenyl)-1-phenyl-1,3-dihydro-2H-
benzo[e]indol-2-one (6). A 10 mL oven-dried Schlenk tube
equipped with a magnetic stirring bar, 3a (0.1 mmol, 1.0 equiv,
36.5 mg), 1-iodooctane (0.2 mmol, 2.0 equiv, 48 mg), Cs2CO3 (0.1
mmol, 1.0 equiv, 32.5 mg), and DMSO (1.0 mL) was vigorously
stirred at 40 °C for 4 h. Then the mixture was cooled to room
temperature, added water (5 mL), extracted with EtOAc (5 mL × 3).
The combined organic phases were dried over anhydrous Na2SO4,
filtered and concentrated in vacuo. Purification by PTLC on silica gel
(petroleum ether/ethyl acetate = 10/1) afforded the title compound 6
in 93% yield (44.3 mg) as a white solid; mp: 88−89 °C; Rf = 0.40
(petroleum ether/ethyl acetate = 10/1); 1H NMR (400 MHz,
CDCl3) δ 9.63 (s, 1H), 8.02 (d, J = 8.6 Hz, 1H), 7.88 (d, J = 8.1 Hz,
1H), 7.42 (dd, J = 18.1, 8.5 Hz, 2H), 7.34 (t, J = 7.4 Hz, 1H), 7.27−
7.19 (m, 6H), 7.13−7.06 (m, 2H), 6.59 (s, 1H), 4.02−3.89 (m, 2H),
2.03 (s, 3H), 1.89−1.84 (m, 2H), 1.50−1.28 (m, 10H), 0.92 (t, J =
6.7 Hz, 3H). 13C{1H} NMR (100 MHz, CDCl3) δ 182.9, 155.3,
139.5, 137.6, 131.1, 130.9, 130.7, 130.6, 130.2, 129.2, 129.1, 128.4,
127.8, 127.5, 127.2, 126.1, 124.1, 123.7, 122.1, 119.9, 110.2, 63.8,
40.9, 31.7, 29.2, 29.2, 27.8, 26.9, 22.6, 20.6, 14.1. HRMS (ESI) m/z:
[M + Na]+ calcd for C33H35NO2Na 500.2560, found 500.2553.
5,5′-Dimethyl-3,3′-diphenyl-[3,3′-bibenzofuran]-
2,2′(3H,3′H)-dione (7).15b The representative general procedure
mentioned above was followed. Purification by PTLC on silica gel
(petroleum ether/ethyl acetate = 5/1) afforded the title compound 7
1
ether/ethyl acetate = 5/1); H NMR (400 MHz, CDCl3) δ 9.23 (s,
1H), 8.46 (s, 1H), 7.29 (d, J = 5.9 Hz, 3H), 7.22−7.13 (m, 3H), 7.05
(s, 2H), 6.87 (t, J = 7.6 Hz, 2H), 6.73 (s, 1H), 2.21 (s, 3H). 13C{1H}
NMR (100 MHz, CDCl3) δ 183.1, 153.8, 139.2, 138.0, 134.5, 130.7,
129.6, 129.5, 129.0, 128.8, 128.7, 127.9, 127.3, 126.7, 124.8, 119.6,
112.0, 62.8, 20.8. HRMS (EI) m/z: [M]+ calcd for
C21H16ClNO2349.0868, found 349.0870.
5-Bromo-3-(2-hydroxy-5-methylphenyl)-3-phenylindolin-2-
one (4n). The representative general procedure mentioned above was
followed. Purification by PTLC on silica gel (petroleum ether/ethyl
acetate = 5/1) afforded the title compound 4o in 63.6% yield (50.0
mg) as a yellow solid; mp: 227−228 °C; Rf = 0.37 (petroleum ether/
1
in 8% yield as a white solid; H NMR (400 MHz, CDCl3) δ 7.49−
7.25 (m, 6H), 7.20 (d, J = 8.1 Hz, 1H), 7.01 (d, J = 8.2 Hz, 1H), 2.27
(s, 3H). 13C{1H} NMR (100 MHz, CDCl3) δ 173.7, 151.4, 133.0,
131.2, 130.8, 130.6, 130.6, 130.2, 128.8, 128.6, 128.0, 127.5, 127.3,
126.9, 126.2, 110.7, 110.3, 21.4.
1
ethyl acetate = 5/1); H NMR (400 MHz, CDCl3) δ 9.44 (s, 1H),
2-(2-Hydroxyphenyl)-N-(naphthalen-2-yl)acetamide (9).20
A
9.00 (s, 1H), 7.27−7.20 (m, 3H), 7.15 (d, J = 7.7 Hz, 2H), 7.05 (t, J =
8.8 Hz, 2H), 6.92−6.85 (m, 3H), 6.78 (s, 1H), 2.82 (dt, J = 13.7, 6.8
Hz, 1H), 2.16 (s, 3H), 1.17 (dd, J = 8.9, 7.2 Hz, 6H). 13C{1H} NMR
(100 MHz, CDCl3) δ 183.2, 153.5, 139.1, 138.8, 134.9, 131.6, 130.7,
129.9, 129.8, 129.7, 129.0, 128.0, 127.0, 125.2, 119.4, 116.0, 112.6,
62.6, 20.8. HRMS (EI) m/z: [M]+ calcd for C21H16BrNO2349.0364,
found 393.0364.
3-(2-Hydroxy-5-methylphenyl)-5-isopropyl-3-phenylindo-
lin-2-one (4o). The representative general procedure mentioned
above was followed. Purification by PTLC on silica gel (petroleum
ether/ethyl acetate = 5/1) afforded the title compound 4p in 54%
yield (38.0 mg) as a yellow solid; mp: 75−76 °C; Rf = 0.37
(petroleum ether/ethyl acetate = 5/1); 1H NMR (400 MHz, CDCl3)
δ 9.45 (s, 1H), 9.01 (s, 1H), 7.28−7.22 (m, 3H), 7.16 (d, J = 7.7 Hz,
2H), 7.06 (t, J = 8.8 Hz, 2H), 6.93−6.85 (m, 3H), 6.79 (s, 1H),
2.88−2.79 (m, 1H), 2.18 (s, 3H), 1.18 (dd, J = 8.9, 7.2 Hz, 6H).
13C{1H} NMR (100 MHz, CDCl3) δ 183.8, 154.4, 144.3, 140.3,
10 mL Schlenk tube was charged with 8 (26.8 mg, 0.20 mmol), 2a
(57.2 mg, 0.40 mmol), and I2 (50.6 mg, 0.20 mmol), under standard
reaction conditions. The vial stirred at 80 °C for 12 h. The mixture
was then cooled to room temperature, diluted with CH2Cl2 (2 mL),
filtered through a Celite pad, and concentrated in vacuo. The residue
was purified by flash column chromatography on silica gel, eluting
with EtOAc/hexane (1:5, v/v), to afford the product 9 in 83% yield.
1H NMR (400 MHz, DMSO) δ 10.26 (s, 1H), 9.52 (s, 1H), 8.31 (s,
1H), 7.90−7.72 (m, 3H), 7.61 (d, J = 8.8 Hz, 1H), 7.42 (dt, J = 14.7,
7.2 Hz, 2H), 7.18 (d, J = 7.4 Hz, 1H), 7.08 (t, J = 7.6 Hz, 1H), 6.88−
6.67 (m, 2H), 3.67 (s, 2H). 13C{1H} NMR (100 MHz, DMSO) δ
170.3, 155.8, 137.4, 133.9, 131.4, 130.1, 128.8, 128.2, 127.9, 127.7,
126.8, 124.9, 122.9, 120.4, 119.3, 115.5, 115.4, 38.5.
Control Experiments.
(a) Radical trapping experiment. A 10 mL Schlenk tube was
charged with 1a (44.8 mg, 0.20 mmol), 2a (57.2 mg, 0.40
mmol) I2 (50.6 mg, 0.20 mmol), and TEMPO (62.4 mg, 0.4
mmol, 2.0 equiv) under standard reaction conditions. The vial
was evacuated and filled with N2, and stirred at 80 °C for 12 h.
The mixture was then cooled to room temperature, diluted
with CH2Cl2 (2 mL), filtered through a Celite pad, analyzed by
GCMS, and concentrated in vacuo. The residue was purified
by flash column chromatography on silica gel, eluting with
EtOAc/hexane (1:5, v/v), to afford the product 3a (yield =
12%).
(b) A 10 mL Schlenk tube was charged with 7 (44.6 mg, 0.10
mmol), 2a (57.2 mg, 0.40 mmol), and I2 (50.6 mg, 0.20
mmol), under standard reaction conditions. The vial stirred at
80 °C for 12 h. The mixture was then cooled to room
temperature, diluted with CH2Cl2 (2 mL), filtered through a
Celite pad, and concentrated in vacuo. The residue was
purified by flash column chromatography on silica gel, eluting
137.2, 132.9, 130.5, 129.9, 129.2, 128.9, 127.5, 126.6, 126.2, 125.5,
125.1, 119.8, 111.0, 63.1, 33.9, 24.5, 23.9, 20.8. HRMS (EI) m/z:
[M]+ calcd for C24H23NO2 357.1728, found 357.1729.
1-(5-Methyl-2-(4-nitrophenoxy)phenyl)-1-phenyl-1,3-dihy-
dro-2H-benzo[e]indol-2-one (5). A 10 mL oven-dried Schlenk
tube equipped with a magnetic stirring bar, 3a (0.1 mmol, 1.0 equiv,
36.5 mg), 1-fluoro-4-nitrobenzene (0.2 mmol, 2.0 equiv, 28.2 mg),
Cs2CO3 (0.1 mmol, 1.0 equiv, 32.5 mg), and DMSO (1.0 mL) was
vigorously stirred at 40 °C for 4 h. Then the mixture was cooled to
room temperature, added water (5 mL), extracted with EtOAc (5 mL
× 3). The combined organic phases were dried over anhydrous
Na2SO4, filtered and concentrated in vacuo. Purification by PTLC on
silica gel (petroleum ether/ethyl acetate = 5/1) afforded the title
compound 5 in 99% yield (48.1 mg) as a white solid; mp: 197−198
1
°C; Rf = 0.45 (petroleum ether/ethyl acetate = 5/1); H NMR (400
MHz, DMSO-d6) δ 10.71 (s, 1H), 7.76 (d, J = 9.0 Hz, 3H), 7.60 (d, J
2971
https://dx.doi.org/10.1021/acs.joc.0c02846
J. Org. Chem. 2021, 86, 2965−2973

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
Qinghua Yang − State Key Laboratory of Chemo/Biosensing
and Chemometrics, Advanced Catalytic Engineering Research
Center of the Ministry of Education, College of Chemistry and
Chemical Engineering, Hunan University, Changsha 410082,
P. R. China
Shuang-Feng Yin − State Key Laboratory of Chemo/
Biosensing and Chemometrics, Advanced Catalytic
Engineering Research Center of the Ministry of Education,
College of Chemistry and Chemical Engineering, Hunan
University, Changsha 410082, P. R. China
with EtOAc/hexane (1:5, v/v), to afford the product 3a 83%
yield.
(c) A 10 mL Schlenk tube was charged with 7 (22.3 mg, 0.05
mmol), 1d (23.8 mg, 0.10 mmol), 2a (57.2 mg, 0.40 mmol),
and I2 (50.6 mg, 0.20 mmol), under standard reaction
conditions. The vial stirred at 80 °C for 12 h. The mixture
was then cooled to room temperature, diluted with CH2Cl2 (2
mL), filtered through a Celite pad, and concentrated in vacuo.
The residue was purified by flash column chromatography on
silica gel, eluting with EtOAc/hexane (1:5, v/v), to afford the
product 3a and 3d in 82% and 56% yields, respectively.
(d) A 10 mL Schlenk tube was charged with 1a (44.8 mg, 0.20
mmol), 2a (57.2 mg, 0.40 mmol), TBPB (77.6 mg, 0.40
mmol), and I2 (5.0 mg, 0.02 mmol) under standard reaction
conditions. The vial was stirred at 80 °C for 12 h. The mixture
was then cooled to room temperature, diluted with CH2Cl2 (2
mL), filtered through a Celite pad, and concentrated in vacuo.
The residue was purified by flash column chromatography on
silica gel, eluting with EtOAc/hexane (1:5, v/v), to afford the
product 3a (yield = 84%).
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.joc.0c02846
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
The authors thank the Natural Science Foundation of China
(21676076, 21878071, and 21971060), Hu-Xiang High Talent
in Hunan Province (2018RS3042), and Recruitment Program
for Foreign Experts of China (WQ20164300353) for financial
support. R.Q. thanks Prof. Nobuaki Kambe (Osaka University)
for helpful discussion.
ASSOCIATED CONTENT
■
sı
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.joc.0c02846.
Detailed experimental procedures, characterization data,
REFERENCES
■
1
copies of the H, 13C NMR spectra (PDF)
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CCDC 2003926 and 2010035 contain the supplementary
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AUTHOR INFORMATION
Corresponding Authors
■
Zhihong Peng − State Key Laboratory of Chemo/Biosensing
and Chemometrics, Advanced Catalytic Engineering Research
Center of the Ministry of Education, College of Chemistry and
Chemical Engineering, Hunan University, Changsha 410082,
P. R. China; Email: pzh7251@hnu.edu.cn
Renhua Qiu − State Key Laboratory of Chemo/Biosensing
and Chemometrics, Advanced Catalytic Engineering Research
Center of the Ministry of Education, College of Chemistry and
Chemical Engineering, Hunan University, Changsha 410082,
P. R. China; orcid.org/0000-0002-8423-9988;
Email: renhuaqiu1@hnu.edu.cn
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Center of the Ministry of Education, College of Chemistry and
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Provincial Key Lab of Fine Chem, Hainan University,
Haikou 570228, China
Zhiqing Wang − State Key Laboratory of Chemo/Biosensing
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Center of the Ministry of Education, College of Chemistry and
Chemical Engineering, Hunan University, Changsha 410082,
P. R. China
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