Visible-Light-Mediated Cyclopropanation Reactions of 3-Diazooxindoles with Arenes

Article abstract of DOI:10.1021/acs.joc.1c00418

The cyclopropanation reaction of 3-diazooxindoles with arenes was first accomplished using visible-light irradiation. A series of spiro[norcaradiene-7,3′-indolin]-2′-ones were synthesized for the first time in high yields and with excellent diastereoselectivities. The synthetic usefulness of this catalyst-free photochemical methodology is illustrated by the further controllable rearrangement and epoxidation reactions.

Full text of DOI:10.1021/acs.joc.1c00418

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Article
Visible-Light-Mediated Cyclopropanation Reactions of
3‑Diazooxindoles with Arenes
Shuai Zhao,‡ Xiang-Xiang Chen,‡ Nan Gao, Mingcheng Qian, and Xin Chen*
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ABSTRACT: The cyclopropanation reaction of 3-diazooxindoles with arenes was first accomplished using visible-light irradiation. A
series of spiro[norcaradiene-7,3′-indolin]-2′-ones were synthesized for the first time in high yields and with excellent
diastereoselectivities. The synthetic usefulness of this catalyst-free photochemical methodology is illustrated by the further
controllable rearrangement and epoxidation reactions.
then, the norcaradiene−cycloheptatriene (NCD−CHT) equi-
librium has been extensively studied to understand its
mechanism and the factors that influence the ratio of the
two tautomers (Scheme 1a).6 The Buchner reaction represents
one of the most powerful methods of transforming stable
aromatic rings to much more reactive systems.7 Typically,
precious transition-metal catalysts are required to access a
metal carbene intermediate, which then undergoes a cyclo-
propanation reaction with arenes.8 In contrast, the visible-light-
mediated metal-free Buchner reaction has remained vastly
underexplored until very recently. Koenigs and co-workers
reported the metal-free visible light photolysis of aryl
diazoacetates with arenes as the solvents (Scheme 1b).3b
The norcaradiene-type products could be obtained in
moderate yields and with excellent diastereoselectivities.
According to the literature, the slow addition of the diazo
components is crucial to obtain satisfactory results,3d−f which
is probably due to the side reactions caused by the photolysis
of aryl diazoacetates. We wonder whether norcaradiene
INTRODUCTION
■
Carbenes represent some of the most important synthetic
intermediates in modern organic chemistry. The multifarious
transformations of carbenes, including cycloaddition reactions
and C−H and X−H bond insertion reactions, provide an
efficient way to construct complex molecules. Transition-
metal-catalyzed carbene transfer reactions have made great
progress over the past few decades.1 However, the develop-
ment of practical, sustainable, and environment-friendly metal-
free carbene transfer reactions is in high demand today.
Recently, visible-light-mediated metal-free carbene transfer
reactions have attracted a lot of attention due to their simple
operation and tolerance for moisture and oxygen.2 Typical
carbene transfer reactions, such as cycloaddition, C−H and X−
H bond insertion, olefination, and rearrangement reactions,
have been successfully accomplished under visible-light
irradiation.3 Compared to the conventional metal-free carbene
transfer reactions mediated by UV light irradiation,4 these
approaches could decompose the diazo compound under mild
conditions without side reactions related to the high-energy
UV light. Nevertheless, visible-light-mediated carbene transfer
reactions are so far mainly limited to the application of aryl
diazoacetates,3a thus restricting their application in the
construction of complex scaffolds.
Received: February 20, 2021
The addition of diazo compounds to arenes, providing
monocyclic cycloheptatriene via the ring expansion of bicyclic
norcaradiene, was first described by Buchner in 1885.5 Since
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A

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Scheme 1. Cyclopropanation Reactions of Diazo Compounds with Arenes
a
products could be obtained in higher yields and in a one-pot
approach if more stable diazoalkanes, such as cyclic 3-
diazooxindole 1, were used.9 Novel and interesting spiro-
[norcaradiene-7,3′-indolin]-2′-one will be identified for the
first time (Scheme 1c). Recently, Koenigs and co-workers
described the photochemical O−H functionalization reaction
of acidic alcohols with 3-diazooxindoles, which was the first
application of this cyclic diazoamide in a visible-light-mediated
carbene transfer reaction.3a
Spiro cyclopropyl oxindoles have stimulated intense research
interest10 for their potentially interesting biological activities11
and utilities as synthetic intermediates.12 3-Diazooxindoles
have been used in different metal-catalyzed carbene transfer
reactions to give spirooxindoles.13 However, the cyclo-
propanation reactions between 3-diazooxindoles and arenes
have never been studied before. With our strong interest in
developing practical methods to construct spirooxindoles14
and inspiration from the fast growth of visible-light-mediated
carbene transfer reactions, we began to study the visible-light-
mediated cyclopropanation reaction between 3-diazooxindoles
and arenes.
Table 1. Optimization of Reaction Conditions
b
entry
concentration (mol/L)
t (h)
yield (%)
c
1
0.1
0.1
0.2
0.05
0.02
0.01
0.01
0.01
0.1
24
12
12
12
12
12
24
24
24
24
NR
23
19
32
59
64
82
84
27
NR
2
3
4
5
6
7
d
8
e
9
f
10
0.01
a
Unless otherwise noted, 1a (0.1 mmol) was dissolved in benzene
(2a), and the mixture was stirred at room temperature under
irradiation of blue LEDs (470 nm, 6 W). Isolated yield. The
reaction was carried out with 1a (0.1 mmol) and benzene (2a, 0.5
mmol) in 1 mL of CH2Cl2. The reaction was carried out under a N2
atmosphere. The reaction was carried out with a slow addition of 1a
(0.1 mmol in 0.5 mL benzene) to benzene (0.5 mL) for 3 h. The
b
c
Herein we report the first example of a cyclopropanation
reaction of 3-diazooxindole with an arene. The spiro-
[norcaradiene-7,3′-indolin]-2′-ones were synthesized by visi-
ble-light-mediated carbene transfer reactions in moderate to
high yields and with excellent diastereoselectivities. The ring-
expansion products, cycloheptatrienes, could not be detected
in this methodology.
d
e
f
reaction was carried out in the dark.
was detected, and most of the diazooxindole was recovered.
Then, we tried to use benzene 2a both as the reactant and the
solvent. The cyclopropanation product 3a was successfully
obtained, albeit in a low yield, when the concentration of 1a
was 0.1 M (Table 1, entry 2). This novel spiro[norcaradiene-
7,3′-indolin]-2′-one was synthesized for the first time, and the
diastereoselectivity was very high. Then, different concen-
RESULTS AND DISCUSSION
■
We initiated the study by investigating the reaction of 3-
diazooxindole 1a with 5 equiv of benzene 2a in CH2Cl2 under
the irradiation of blue LEDs (470 nm) at room temperature
(Table 1, entry 1). After 24 h, no cyclopropanation product
B
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a
Scheme 2. Scope of 3-Diazooxindoles
a
Reaction conditions are as follows: 1 (0.1 mmol) was dissolved in benzene (2a, 10 mL), and the mixture was stirred at room temperature under
b
irradiation of blue LEDs (470 nm, 6 W). Yields refer to isolated products. Yield of 72 h.
trations of 1a were screened to increase the yield. It was found
that a lower concentration was more suitable for the
cyclopropanation reaction, and 3a could be isolated in 64%
yield after 12 h when 0.01 M of 1a was used (Table 1, entry 6).
This is probably because of the higher equivalent of benzene at
a lower concentration of 3a. Extending the reaction time to 24
h gave 3a in 82% yield and with an excellent diastereose-
lectivity (Table 1, entry 7). Notably, the norcaradiene-type
product 3a was the sole reaction product, and no cyclo-
heptatriene formation was observed. The competing sp2 C−H
insertion product was also not detected. For comparison, the
reaction was also conducted under a N2 atmosphere (Table 1,
entry 8). The desired product was isolated in almost the same
yield with the reaction under air, which showed that this
cyclopropanation reaction had a good tolerance for air and
moisture. We also tried Koenigs’ conditions3b by adding the
diazo 1a to benzene for 3 h (Table 1, entry 9). The yield was
very low after another 21 h stirring. Importantly, the control
experiment showed that no product was detected when the
reaction was conducted in the dark (Table 1, entry 10).
With the optimal reaction conditions established, the
substrate scope of this photochemical cyclopropanation
reaction was investigated. The reaction time was set to 24 h
for comparison unless otherwise noted, although the reaction
could not go to completion in some cases. The N-substituents
of the 3-diazooxindoles 1 have a great impact on the reaction.
Substrates with electron-donating N-substituents gave much
higher yields than those with electron-withdrawing ones (3a
and 3c versus 3d and 3e). The best yield was obtained using
the N-methyl substrate (3a). With this substrate, a 1 mmol
scale reaction was conducted. The desired product could be
obtained in 89% yield, although a longer reaction time was
needed. 3-Diazooxindole without any N-substituent gave only
a 22% yield of the cyclopropanation product after 72 h due to
the massive amount of diazo substrate left (3b). The absolute
configuration of this novel spiro[norcaradiene-7,3′-indolin]-2′-
C
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a
Scheme 3. Scope and Limitations of Arenes
a
Reaction conditions are as follows: 1a (0.1 mmol) was dissolved in the arene (2, 10 mL), and the mixture stirred at room temperature under
irradiation of blue LEDs (470 nm, 6 W). Yields refer to isolated products, and rr is short for regioisomer ratio, which was determined by 1H NMR.
b
The reaction was carried out with 1a (0.1 mmol) and arene (2, 0.5 mmol) in 1 mL of CH2Cl2 for 72 h.
one was unambiguously determined by X-ray crystallography
(Scheme 2). Then 3-diazooxindoles with different substituents
on the phenyl ring were investigated under the optimal
reaction conditions. Substituents on the 5, 6, or 7 position of 3-
diazooxindoles 1 had little influence on the cyclopropanation
reaction (3f−3p). Additionally, the norcaradiene-type prod-
ucts were obtained in high yields and with excellent
diastereoselectivities. However, when 4-substituted diazoox-
indoles were used, the desired cyclopropanation products
could not be detected (3q−3s). This is probably because of
the large steric hindrance from 4-substituents, which could be
easily predicted from the X-ray crystallography of 3a.
Then, the scope of the arenes was investigated with 3-
diazooxindole 1a (Scheme 3). The substituents of the arenes
have significant effects on the regioselectivity of this photo-
chemical carbene transfer reaction. Moreover, competing C−H
insertion reactions can also occur. When alkyl-substituted
benzenes were used, the cyclopropanation products could be
obtained in moderate to high yields and with excellent
diastereoselectivities (3t−3w). However, the regioselectivity of
this reaction was very low, except for p-xylene (3v). Halo-
substituted substrates also gave the desired products in high
yields, albeit with no regioselectivity (3x and 3y). Interestingly,
when anisole was used, the C−H insertion product 4z was
obtained instead of the cyclopropanation product 3z. This is
probably due to the activation effect of the methoxy group
toward the electrophile. However, we could not completely
rule out the possibility that cyclopropane 3z was indeed
formed and rearranged to 4z under the reaction conditions.
Notably, no cycloheptatriene formation was observed for any
of the substrates.
Next, other arenes besides benzene were examined (Scheme
3). Because they were all solid at room temperature, CH2Cl2
was used as the reaction solvent. The cyclopropanation of
diazooxindole 1a with naphthalene furnished the desired
product 3aa in moderate yield with an excellent diaster-
eoselectivity and regioselectivity after 72 h. However, none of
the tested heteroaromatic substrates could give the expected
norcaradiene type products, and most of them remained intact
under the reaction conditions. Only a small amount of the C−
H insertion product 4ac was isolated. In contrast, Davies and
co-workers have reported the cyclopropanation or C−H
insertion reactions of aryldiazoacetate with these heteroar-
omatic substrates in CH2Cl2 under blue light irradiation.3g
These results suggest that diazooxindoles are less reactive
carbene precursors than aryldiazoacetate under photochemical
catalysis.
D
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Then, the stability and synthetic utility of these novel
spiro[norcaradiene-7,3′-indolin]-2′-ones were studied. Norcar-
adiene is well-known for undergoing a Buchner ring-expansion
reaction to give cycloheptatriene. However, substituents with a
strong π-acceptor at C-7 tend to shift this equilibrium to the
norcaradiene side.6 In this work, all the norcaradiene-type
products 3 are quite stable, and no cycloheptatriene was
detected. In addition, norcaradiene has been reported to
rearrange to the C−H insertion product in thermal, photo-
chemical, or acid conditions.15 We have noticed that
norcaradiene 3n was partially converted to the C−H insertion
product 4n in the process of silica gel column chromatography
purification.15c This result indicates that silica gel might assist
the cyclopropane opening. Additionally, the subsequent proton
transfer gave the product. Therefore, the silica gel-promoted
cyclopropane-opening reaction of selected norcaradienes was
studied in detail, and the results are outlined in Scheme 4. The
which is an unproductive and reversible pathway. Then, the
electrophilic singlet carbene A is trapped by an aromatic ring
to produce norcaradiene 3a.
1
CONCLUSIONS
■
In conclusion, we have developed the first examples of
cyclopropanation reactions of 3-diazooxindoles with arenes. A
series of novel spiro[norcaradiene-7,3′-indolin]-2′-ones were
produced in moderate to high yields and with excellent
diastereoselectivities by visible light irradiation. The synthetic
application of this methodology is well demonstrated by the
controllable rearrangement and epoxidation reactions. More-
over, this work will broaden the application of visible-light-
mediated carbene transfer reactions.
EXPERIMENTAL SECTION
■
General Information. All glassware was thoroughly oven-dried.
Chemicals and solvents were either purchased from commercial
suppliers or purified by standard techniques. Thin-layer chromatog-
raphy plates were visualized by exposure to ultraviolet light or staining
with phosphomolybdic acid, followed by heating on a hot plate. Flash
chromatography was carried out using silica gel (160−200 mesh). 1H
NMR and 13C NMR spectra were recorded using Bruker AV-300, AV-
400, and AV-500 spectrometers. Chemical shifts (δ)are given in parts
per million relative to tetramethylsilane (TMS). Data for 1H NMR are
reported as follows: chemical shift (δ ppm), multiplicity (s = singlet, d
= doublet, t = triplet, q = quartet, m = multiplet, dd = doublet of
doublet, td = triplet of doublet), integration, coupling constant (Hz),
and assignment. The spectra were recorded in either CDCl3 or
(CD3)2SO as the solvent at room temperature. TMS served as
internal standard (δ = 0 ppm) for 1H NMR, and CDCl3 served as an
internal standard (δ = 77.00 ppm) for 13C{H} NMR. High-resolution
mass spectra were acquired on a Thermo Orbitrap Elite instrument
(Agilent, Palo Alto, CA).
Scheme 4. (a) Silica Gel-Promoted Cyclopropane-Opening
Reaction of Norcaradienes and (b) Monoepoxidation of
Norcaradiene 3a
Synthesis of Diazo Substrates 1. Diazo substrates 1 were
prepared with modified methods according to the literatures.17
A
mixture of isatin (147 mg, 1 mmol) and TsNHNH2 (205 mg, 1.1
mmol, 1.1 equiv) in THF (5 mL) was stirred at 60 °C (oil bath) for 2
h. Then, the mixture was filtered. The filter cake was stirred in a 0.2 N
NaOH aqueous solution at 60 °C (oil bath) for 1 h. The reaction
mixture was extracted with EtOAc. The combined organic layers were
dried by Na2SO4 and then concentrated in vacuo. The crude product
was purified by flash column chromatography (eluted with EtOAc/
petroleum ether 1:3) to afford 3-diazoindolin-2-one.
To a stirred solution of 3-diazoindolin-2-one (159 mg, 1 mmol) in
CH3CN (5 mL) was added K2CO3 (414 mg, 3 mmol, 3 equiv) at
room temperature. After 5 min, CH3I (156 mg, 1.1 mmol, 1.1 equiv)
was added via syringe. The reaction mixture was stirred at room
temperature until 3-diazoindolin-2-one was fully consumed (moni-
tored by TLC). The reaction was then diluted with EtOAc and H2O.
The aqueous layer was extracted three times with EtOAc. The
combined organic layers were washed with water and brine, dried over
Na2SO4, and concentrated in vacuo. The resulting residue was purified
by flash column chromatography (eluted with EtOAc/petroleum
ether 1:5) to give N-methyl-3-diazoindolin-2-one 1.
C−H insertion product 4a was obtained in quantitative yield
after 29 h. Unsurprisingly, norcaradiene 3n was the most
unstable substrate under this condition and gave the C−H
insertion product 4n in 82% yield after 12 h. Obviously, the
substituents of the norcaradienes 3 have a great impact on this
silica gel-promoted cyclopropane-opening reaction. Moreover,
treating 3a with the Camps condition16 (m-CPBA/KF) gave
the monoepoxidation product 5a as a single diastereomer.8g By
using this nonacidic epoxidation condition, possible rearrange-
ment reactions of norcaradiene 3a and epoxide 5a were
avoided.
1a−1m, 1p, 1r, and 1s are known compounds, and their spectra are
all consistent with literature values.
3-Diazo-1-methyl-7-nitroindolin-2-one (1n). Yellow solid, 73%
1
yield (159.7 mg), Rf = 0.3 (EtOAc/petroleum ether 1:5). H NMR
(400 MHz, CDCl3): δ 7.60 (dd, J1 = 8.32 Hz, J2 = 0.9 Hz, 1H), 7.37
(dd, J1 = 7.6 Hz, J2 = 0.9 Hz, 1H), 7.15 (t, J = 8.0 Hz, 1H), 3.36 (s,
3H). 13C{1H} NMR (75 MHz, CDCl3): δ 166.6, 135.6, 127.6, 121.6,
121.5, 121.4, 120.6, 120.5, 30.5. HRMS (ESI) m/z: calcd for
C9H7N4O3 [M + H]+ 219.0513, found 219.0511.
3-Diazo-1-methyl-7-(trifluoromethyl)indolin-2-one (1o). Yellow
solid, 76% yield (183.3 mg), Rf = 0.2 (EtOAc/petroleum ether 1:5).
1H NMR (400 MHz, CDCl3): δ 7.48 (d, J = 8.0 Hz, 1H), 7.34 (d, J =
7.5 Hz, 1H), 7.14 (t, J = 7.8 Hz, 1H), 3.50 (d, J = 2.4 Hz, 3H).
Finally, based on the experimental results and literature
reports,3d,g,h a plausible mechanism for this cyclopropanation
reaction is postulated in Scheme 5. The irradiation of 3-
diazooxindole 1a with blue LEDs gives excited state 1a*, which
expels dinitrogen to afford a singlet carbene 1A. The
1
3
intersystem crossing (ISC) of A gives a triplet carbene A,
E
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Scheme 5. Postulated Mechanism of the Cyclopropanation Reaction
13C{1H} NMR (100 MHz, CDCl3): δ 166.9, 131.8, 123.6, 123.5,
123.4, 123.3, 122.3, 121.4, 119.1, 113.3, 112.9, 29.5, 29.4. HRMS
(ESI) m/z: calcd for C10H7F3N3O [M + H]+ 242.0536, found
242.0534.
121.5, 109.5, 41.1, 16.4. HRMS (ESI) m/z: calcd for C14H12NO [M +
H]+ 210.0913, found 210.0915.
1′-Benzylspiro[bicyclo[4.1.0]heptane-7,3′-indoline]-2,4-dien-2′-
one (3c). Procedure A, red solid, 80% yield (23.9 mg), Rf = 0.3
(EtOAc/petroleum ether 1:5). 1H NMR (400 MHz, CDCl3): δ 7.35−
7.24 (m, 5H), 7.11 (t, J = 7.7 Hz, 1H), 6.87 (t, J = 7.8 Hz, 1H), 6.81
(d, J = 7.8 Hz, 1H), 6.69 (d, J = 7.6 Hz, 1H), 6.49 (dd, J1 = 7.3 Hz, J2
= 2.9 Hz, 2H), 6.16−6.12 (m, 2H), 5.02 (s, 2H), 3.29 (t, J = 3.0 Hz,
2H). 13C{1H} NMR (125 MHz, CDCl3): δ 179.4, 143.8, 136.4, 128.8,
127.6, 127.5, 126.3, 126.2, 126.1, 124.0, 122.9, 121.6, 108.6, 44.5,
41.5, 15.9. HRMS (ESI) m/z: calcd for C21H18NO [M + H]+
300.1383, found 300.1384
3-Diazo-4-fluoro-1-methylindolin-2-one (1q). Red solid, 85%
1
yield (162.9 mg), Rf = 0.3 (EtOAc/petroleum ether 1:5). H NMR
(400 MHz, (CD3)2SO): δ 7.22 (dd, J1 = 13.9 Hz, J2 = 8.0 Hz, 1H),
7.01−6.93 (m, 2H), 3.25 (s, 3H). 13C{1H} NMR (75 MHz,
(CD3)2SO): δ 165.7, 156.9, 136.4, 136.3, 126.8, 126.7, 108.8,
108.5, 105.9, 105.8, 103.1, 102.9, 27.2. HRMS (ESI) m/z: calcd for
C9H7FN3O [M + H]+ 192.0568, found 192.0567.
General Procedure for the Visible-Light-Mediated Cyclo-
propanation Reactions of 3-Diazooxindoles with Arenes.
Procedure A. In a test tube and under air, 3-diazooxindole 1 (0.1
mmol) was dissolved in benzene 2 (10 mL), and the reaction mixture
stirred at room temperature under irradiation of blue LEDs (470 nm,
6W) for 24 h. Then, the reaction mixture was concentrated and
directly purified by flash column chromatography (eluted with
EtOAc/petroleum ether 1:5) to give products 3 or 4.
Procedure B. In a test tube and under air, 3-diazooxindole 1 (0.1
mmol) and arene 2 (0.5 mmol, 5 equiv) were dissolved in DCM (1
mL), and the reaction mixture was stirred at room temperature under
irradiation of blue LEDs (470 nm, 6W) for 24 h. Then, the reaction
mixture was concentrated and directly purified by flash column
chromatography (eluted with EtOAc/petroleum ether 1:5) to give
products 3 or 4.
The procedure for the 1 mmol scale reaction is as follows: in a 250
mL round-bottomed flask and under air, 3-diazooxindole 1a (1
mmol) was dissolved in benzene 2 (100 mL), and the reaction
mixture was stirred at room temperature under irradiation of blue
LEDs (470 nm, 6W) for 72 h. Then, the reaction mixture was
concentrated and directly purified by flash column chromatography
(eluted with EtOAc/petroleum ether 1:5) to give product 3a (89%
yield, 189.7 mg).
1′-Acetylspiro[bicyclo[4.1.0]heptane-7,3′-indoline]-2,4-dien-2′-
one (3d). Procedure A, white solid, 37% yield (9.3 mg), Rf = 0.4
1
(EtOAc/petroleum ether 1:5). H NMR (400 MHz, CDCl3): δ 8.35
(d, J = 8.2 Hz, 1H), 7.25 (t, J = 7.9 Hz, 1H), 7.04 (t, J = 7.7 Hz, 1H),
6.55 (dd, J1 = 7.4 Hz, J2 = 2.9 Hz, 2H), 6.16−6.12 (m, 2H), 3.28 (t, J
= 2.6 Hz, 2H), 2.73 (s, 3H). 13C{1H} NMR (125 MHz, CDCl3): δ
180.3, 170.8, 140.8, 127.2, 126.7, 125.6, 124.4, 123.8, 122.3,115.9,
42.4, 26.9, 15.9. HRMS (ESI) m/z: calcd for C16H14NO2 [M + H]+
252.1019, found 252.1018.
tert-Butyl 2′-Oxospiro[bicyclo[4.1.0]heptane-7,3′-indoline]-2,4-
diene-1′-carboxylate (3e). Procedure A, red solid, 42% yield (13.0
1
mg), Rf = 0.3 (EtOAc/petroleum ether 1:5). H NMR (400 MHz,
CDCl3): δ 7.95 (d, J = 8.2 Hz, 1H), 7.26−7.22 (m, 1H), 7.00 (t, J =
7.7 Hz, 1H), 6.67 (d, J = 7.7 Hz, 1H), 6.52 (dd, J1 = 7.4 Hz, J2 = 2.9
Hz, 2H), 6.13−6.09 (m, 2H), 3.26 (t, J = 3.0 Hz, 2H), 1.66 (s, 9H).
13C{1H} NMR (125 MHz, CDCl3): δ 178.1, 149.3, 140.5, 126.9,
126.4, 125.4, 123.9, 123.6, 122.6, 84.3, 42.1, 28.3, 15.6. HRMS (ESI)
m/z: calcd for C19H19NNaO3 [M + Na]+ 332.1257, found 332.1254.
1′,5′-Dimethylspiro[bicyclo[4.1.0]heptane-7,3′-indoline]-2,4-
dien-2′-one (3f). Procedure A, red solid, 99% yield (23.5 mg), Rf =
1
0.3 (EtOAc/petroleum ether 1:5). H NMR (500 MHz, CDCl3): δ
7.03 (dd, J1 = 7.9 Hz, J2 = 0.8 Hz, 1H), 6.79 (d, J = 7.9 Hz, 1H), 6.52
(s, 1H), 6.48 (dd, J1 = 7.3 Hz, J2 = 2.9 Hz, 2H), 6.13−6.09 (m, 2H),
3.3 (s, 3H), 3.22 (dd, J1 = 3.6 Hz, J2 = 2.6 Hz, 2H), 2.26 (s, 3H).
13C{1H} NMR (125 MHz, CDCl3): δ 179.2, 142.3, 130.9, 126.5,
1′-Methylspiro[bicyclo[4.1.0]heptane-7,3′-indoline]-2,4-dien-2′-
one (3a). Procedure A, red solid, 82% yield (18.3 mg), Rf = 0.4
1
(EtOAc/petroleum ether 1:5). H NMR (500 MHz, CDCl3): δ 7.23
(t, J = 7.7 Hz, 1H), 6.93−6.90 (m, 2H), 6.70 (d, J = 7.8 Hz, 1H), 6.48
(dd, J1 = 2.9 Hz, J2 = 7.3 Hz, 2H), 6.13−6.09 (m, 2H), 3.33 (s, 3H),
3.23 (t, J = 3.0 Hz, 2H). 13C{1H} NMR (100 MHz CDCl3): δ 179.2,
144.6, 126.3, 126.2, 126.1, 123.9, 122.9, 121.5, 107.6, 41.4, 27.0, 16.0.
HRMS (ESI) m/z: calcd for C15H13NNaO [M + Na]+ 246.0899,
found 246.0904.
126.4, 126.3, 124.0, 123.8, 107.3, 41.9, 21.1, 21.5, 16.2. HRMS (ESI)
m/z: calcd for C16H15NNaO [M + Na]+ 260.1046, found 260.1060.
5′-Chloro-1′-methylspiro[bicyclo[4.1.0]heptane-7,3′-indoline]-
2,4-dien-2′-one (3g). Procedure A, red solid, 82% yield (21.1 mg), Rf
= 0.3 (EtOAc/petroleum ether 1:5). 1H NMR (400 MHz, CDCl3): δ
7.19 (dd, J1 = 8.3 Hz, J2 = 2.1 Hz, 1H), 6.80 (d, J = 8.3 Hz, 1H), 6.62
(d, J = 2.0 Hz, 1H), 6.51 (dd, J1 = 7.4 Hz, J2 = 2.9 Hz, 2H), 6.13−6.09
(m, 2H), 3.31 (s, 3H), 3.24 (t, J = 3.0 Hz, 2H). 13C{1H} NMR (100
MHz, CDCl3): δ 178.7, 143.2, 127.6, 126.9, 126.5, 125.9, 123.8,
123.2, 108.2, 41.3, 27.1, 15.5. HRMS (ESI) m/z: calcd for
C15H12ClNNaO [M + Na]+ 280.0500, found 280.0506.
Spiro[bicyclo[4.1.0]heptane-7,3′-indoline]-2,4-dien-2′-one (3b).
Procedure A, red solid, 22% yield (4.6 mg), Rf = 0.4 (EtOAc/
1
petroleum ether 1:5). H NMR (400 MHz, CDCl3): δ 8.87 (s, 1H),
7.16 (t, J = 7.6 Hz, 1H), 6.99 (d, J = 7.7 Hz, 1H), 6.88 (t, J = 7.6 Hz,
1H), 6.66 (d, J = 7.6 Hz, 1H), 6.50 (dd, J1 = 7.4 Hz, J2 = 2.8 Hz, 2H),
6.15−6.11 (m, 2H), 3.25 (t, J = 2.9 Hz, 2H). 13C{1H} NMR (125
MHz, CDCl3): δ 181.7, 141.8, 126.5, 126.4, 126.2, 123.9, 123.2,
1′-Methyl-5′-(trifluoromethoxy)spiro[bicyclo[4.1.0]heptane-7,3′-
indoline]-2,4-dien-2′-one (3h). Procedure A, colorless oil, 93% yield
F
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1
(28.6 mg), Rf = 0.4 (EtOAc/petroleum ether 1:5). H NMR (500
MHz, CDCl3): δ 7.09 (dd, J1 = 8.5 Hz, J2 = 1.4 Hz, 1H), 6.85 (d, J =
8.5 Hz, 1H), 6.56 (d, J = 1.0 Hz, 1H), 6.50 (dd, J1 = 5.9 Hz, J2 = 2.4
Hz, 2H), 6.13−6.10 (m, 2H), 3.33 (s, 3H), 3.26 (t, J = 2.4 Hz, 2H).
13C{1H} NMR (125 MHz, CDCl3): δ 178.9, 144.0, 143.9, 143.2,
7′-Bromo-1′-methylspiro[bicyclo[4.1.0]heptane-7,3′-indoline]-
2,4-dien-2′-one (3p). Procedure A, white solid, 69% yield (20.8 mg),
Rf = 0.3 (EtOAc/petroleum ether 1:5). 1H NMR (400 MHz, CDCl3):
δ 7.32 (d, J = 8.2 Hz, 1H), 6.73 (t, J = 7.9 Hz, 1H), 6.58 (d, J = 7.6
Hz, 1H), 6.49 (dd, J1 = 7.5 Hz, J2 = 2.5 Hz, 2H), 6.11−6.09 (m, 2H),
3.73 (s, 3H), 3.25 (s, 2H). 13C{1H} NMR (100 MHz, CDCl3): δ
179.6, 141.7, 131.8, 129.2, 126.7, 123.9, 122.6, 121.6, 102.0, 42.1,
30.8, 14.9. HRMS (ESI) m/z: calcd for C15H13BrNO [M + H]+
302.0175, found 302.0174.
127.2, 126.4, 123.8, 118.9, 116.9, 107.4, 40.9, 27.1, 15.4. HRMS (ESI)
m/z: calcd for C16H13F3NO2 [M + H]+ 308.0893, found 308.0895.
1′-Methyl-5′-nitrospiro[bicyclo[4.1.0]heptane-7,3′-indoline]-2,4-
dien-2′-one (3i). Procedure A, yellow solid, 70% yield (18.8 mg), Rf =
1
1′,3-Dimethylspiro[bicyclo[4.1.0]heptane-7,3′-indoline]-2,4-
0.4 (EtOAc/petroleum ether 1:5). H NMR (400 MHz, CDCl3): δ
dien-2′-one (3t). Procedure A, colorless oil, 88% yield (20.9 mg), Rf =
8.20 (dd, J1 = 8.6 Hz, J2 = 2.2 Hz, 1H), 7.49 (d, J = 2.1 Hz, 1H), 6.94
(d, J = 8.6 Hz, 1H), 6.62 (dd, J1 = 7.4 Hz, J2 = 2.8 Hz, 2H), 6.18−6.14
(m, 2H), 3.39 (s, 3H), 3.34 (t, J = 2.8 Hz, 2H). 13C{1H} NMR (75
MHz, CDCl3): δ 179.4, 150.1, 142.7, 127.1, 126.3, 123.7, 123.4,
118.5, 106.8, 41.2, 27.4, 15.2. HRMS (ESI) m/z: calcd for
C15H13N2O3 [M + H]+ 269.0921, found 269.0913.
6′-Chloro-1′-methylspiro[bicyclo[4.1.0]heptane-7,3′-indoline]-
2,4-dien-2′-one (3j). Procedure A, red solid, 90% yield (23.2 mg), Rf
= 0.3 (EtOAc/petroleum ether 1:5). 1H NMR (500 MHz, CDCl3): δ
6.87 (td, J1 = 9.2 Hz, J2 = 2.3 Hz, 2H), 6.56 (d, J = 8.08 Hz, 1H), 6.47
(dd, J1 = 9.2 Hz, J2 = 3.6 Hz, 2H), 6.13−6.08 (m, 2H), 3.30 (s, 3H),
3.22 (t, J = 3.8 Hz, 2H). 13C{1H} NMR (125 MHz, CDCl3): δ 179.2,
145.8, 132.4, 126.3, 124.4, 123.9, 123.6, 121.3, 108.3, 41.1, 27.1, 15.8.
HRMS (ESI) m/z: calcd for C15H12ClNNaO [M + Na]+ 280.0500,
found 280.0504.
6′-Bromo-1′-methylspiro[bicyclo[4.1.0]heptane-7,3′-indoline]-
2,4-dien-2′-one (3k). Procedure A, white solid, 81% yield (24.5 mg),
Rf = 0.3 (EtOAc/petroleum ether 1:5). 1H NMR (400 MHz, CDCl3):
δ 7.02 (d, J = 11.0 Hz, 2H), 6.48 (t, J = 9.7 Hz, 3H), 6.10 (d, J = 4.0
Hz, 2H), 3.30 (s, 3H), 3.22 (s, 2H). 13C{1H} NMR (100 MHz,
CDCl3): δ 178.9, 145.9, 126.3, 124.9, 124.2, 124.0, 123.9, 120.2,
111.0, 40.9, 27.1, 15.7. HRMS (ESI) m/z: calcd for C15H13BrNO [M
+ H]+ 302.0174, found 302.0173.
1
0.3 (EtOAc/petroleum ether 1:5), regioisomer ratio 2:1. H NMR
(500 MHz, CDCl3): δ 7.22 (td, J1 = 7.8 Hz, J2 = 1.2 Hz, 1H), 6.93−
6.89 (m, 3H), 6.66 (d, J = 7.4 Hz, 1H), 6.50 (dd, J1 = 8.0 Hz, J2 = 1.1
Hz, 0.5H), 6.4 (dd, J1 = 9.4 Hz, J2 = 6.1 Hz, 1H), 6.33 (dd, J1 = 9.5
Hz, J2 = 1.1 Hz, 0.5H), 6.24 (d, J = 6 Hz, 1H), 6.09 (dd, J1 = 9.4 Hz,
J2 = 5.1 Hz, 0.5H), 5.94 (dd, J1 = 9.3 Hz, J2 = 5.4 Hz, 1H), 5.83−5.82
(m, 0.5 H), 3.34 (s, 3H), 3.32 (s, 1.5H). 13C{1H} NMR (125 MHz,
CDCl3): δ 179.4, 179.0, 144.6, 144.5, 134.3, 133.6, 130.1, 126.9,
126.2, 126.1, 126.0, 125.6, 124.0, 122.6, 122.5, 121.7, 121.6, 121.5,
120.6, 119.1, 107.6, 107.5, 41.8, 40.3, 40.0, 39.3, 27.0, 26.9, 23.7, 21.8,
17.5, 16.2. HRMS (ESI) m/z: calcd for C16H15NNaO [M + Na]+
260.1046, found 260.1061.
1′,2,3-Trimethylspiro[bicyclo[4.1.0]heptane-7,3′-indoline]-2,4-
dien-2′-one (3u). Procedure A, white solid, 77% yield (19.4 mg), Rf =
1
0.3 (EtOAc/petroleum ether 1:5), regioisomer ratio 3:1. H NMR
(400 MHz, CDCl3): δ 7.21 (t, J = 7.7 Hz, 1.3H), 6.91−6.88 (m,
2.7H), 6.46 (d, J = 7.5 Hz, 1H), 6.34 (d, J = 7.4 Hz, 0.3H), 6.30 (d, J
= 9.4 Hz, 1H), 5.92−5.86 (m, 1.6H), 3.33 (s, 3H), 3.32 (s, 1H),
3.15−3.12 (m, 1.6H), 3.06 (d, J = 8.7 Hz, 1H), 2.03 (s, 2H), 1.99 (s,
3H), 1.82 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3): δ 179.3,
179.1, 144.6, 144.5, 136.1, 132.0, 127.7, 126.6, 126.3, 125.8, 122.3,
122.2, 121.5, 121.4, 120.4, 107.6, 107.5, 43.1, 39.9, 39.4, 26.9, 20.0,
19.9, 18.4, 17.8, 17.6. HRMS (ESI) m/z: calcd for C17H18NO [M +
H]+ 252.1383, found 252.1384.
1′,7′-Dimethylspiro[bicyclo[4.1.0]heptane-7,3′-indoline]-2,4-
dien-2′-one (3l). Procedure A, red solid, 90% yield (21.4 mg), Rf =
1′,2,5-Trimethylspiro[bicyclo[4.1.0]heptane-7,3′-indoline]-2,4-
1
0.3 (EtOAc/petroleum ether 1:5). H NMR (400 MHz, CDCl3): δ
dien-2′-one (3v). Procedure A, red solid, 64% yield (16.1 mg), Rf =
1
6.95 (d, J = 7.7 Hz, 1H), 6.79 (t, J = 7.7 Hz, 1H), 6.55 (d, J = 7.4 Hz,
1H), 6.47 (dd, J1 = 7.3 Hz, J2 = 2.9 Hz, 2H), 6.12−6.06 (m, 2H), 3.62
(s, 3H), 3.22 (dd, J1 = 3.6 Hz, J2 = 2.6 Hz, 2H), 2.62 (s, 3H). 13C{1H}
NMR (100 MHz, CDCl3): δ 179.9, 142.4, 130.1, 126.9, 126.4, 124.0,
121.4, 120.7, 119.2, 42.5, 30.6, 19.5, 15.2. HRMS (ESI) m/z: calcd for
C16H16NO [M + H]+ 238.1227, found 238.1228.
0.4 (EtOAc/petroleum ether 1:5). H NMR (400 MHz, CDCl3): δ
7.21 (td, J1 = 7.7 Hz, J2 = 0.8 Hz, 1H), 6.92−6.87 (m, 2H), 6.63 (d, J
= 7.5 Hz, 1H), 6.2 (s, 2H), 3.84 (s, 3H), 3.01 (s, 2H), 1.84 (s, 6H).
13C{1H} NMR (125 MHz, CDCl3): δ 179.6, 144.4, 130.1, 125.9,
125.3, 122.4, 122.3, 121.6, 107.5, 42.5, 27.0, 23.2, 17.0. HRMS (ESI)
m/z: calcd for C17H18NO [M + H]+ 252.1383, found 252.1385.
3-(tert-Butyl) 1′-Methylspiro[bicyclo[4.1.0]heptane-7,3′-indo-
line]-2,4-dien-2′-one (3w). Procedure A, colorless oil, 85% yield
(23.7 mg), Rf = 0.3 (EtOAc/petroleum ether 1:5), regioisomer ratio
7′-Chloro-1′-methylspiro[bicyclo[4.1.0]heptane-7,3′-indoline]-
2,4-dien-2′-one (3m). Procedure A, yellow solid, 69% yield (17.8
1
mg), Rf = 0.3 (EtOAc/petroleum ether 1:5). H NMR (400 MHz,
1
CDCl3): δ 7.14 (d, J = 8.2 Hz, 1H), 6.79 (t, J = 7.9 Hz, 1H), 6.55 (d, J
= 7.6 Hz, 1H), 6.49 (dd, J1 = 7.4 Hz, J2 = 2.9 Hz, 2H), 6.12−6.09 (m,
2H), 3.71 (s, 3H), 3.24 (t, J = 3.0 Hz, 2H). 13C{1H} NMR (100
MHz, CDCl3): δ 179.4, 140.3, 128.8, 128.5, 126.6, 123.9, 122.1,
121.1, 115.1, 42.0, 30.5, 15.1. HRMS (ESI) m/z: calcd for
C15H13ClNO [M + H]+ 258.0680, found 258.0681.
1′-Methyl-7′-nitrospiro[bicyclo[4.1.0]heptane-7,3′-indoline]-2,4-
dien-2′-one (3n). Procedure A, colorless oil, 92% yield (24.7 mg), Rf
= 0.4 (EtOAc/petroleum ether 1:5). 1H NMR (400 MHz, CDCl3): δ
7.55 (d, J = 8.2 Hz, 1H), 6.93 (t, J = 8.0 Hz, 1H), 6.79 (d, J = 7.2 Hz,
1H), 6.53 (dd, J1 = 7.4 Hz, J2 = 2.4 Hz, 2H), 6.16−6.12 (m, 2H), 3.23
(s, 3H), 3.32−3.28 (m, 2H). 13C{1H} NMR (100 MHz, CDCl3): δ
179.74, 138.0, 135.1, 129.5, 126.9, 126.2, 123.9, 121.7, 121.0, 41.9,
30.5, 14.3. HRMS (ESI) m/z: calcd for C15H13N2O3 [M + H]+
269.0921, found 269.0920.
1.5:1. H NMR (400 MHz, CDCl3): δ 7.26−7.18 (m, 2.5H), 6.91−
6.86 (m, 5H), 6.64−6.60 (m, 2.5H), 6.55 (d, J = 7.4 Hz, 1H), 6.44
(dd, J1 = 9.2 Hz, J2 = 6.3 Hz, 1.5H), 6.28 (d, J = 6.3 Hz, 1.5H), 6.12
(dd, J1 = 9.8 Hz, J2 = 5.1 Hz, 1H), 5.92 (dd, J1 = 9.2 Hz, J2 = 5.0 Hz,
1.5H), 5.88 (d, J = 5.5 Hz, 1H), 3.34 (s, 4.5H), 3.32 (s, 3H), 3.24−
3.21 (m, 2H), 3.20−3.11 (m, 3H), 1.21 (s, 9H), 0.96 (s, 14H).
13C{1H} NMR (100 MHz, CDCl3): δ 179.4, 179.0, 146.3, 144.6,
146.4, 144.3, 127.2, 127.1, 126.2, 125.9, 125.8, 123.9, 122.9, 122.6,
121.5, 121.1, 120.9, 117.6, 115.3, 107.5, 107.4, 39.6, 38.4, 35.8, 34.8,
29.3, 28.0, 27.0, 26.9, 16.9, 16.5. HRMS (ESI) m/z: calcd for
C19H21NNaO [M + Na]+ 302.1515, found 302.1520.
3-Fluoro-1′-methylspiro[bicyclo[4.1.0]heptane-7,3′-indoline]-
2,4-dien-2′-one (3x). Procedure A, colorless oil, 86% yield (20.7 mg),
Rf = 0.3 (EtOAc/petroleum ether 1:5), regioisomer ratio 1:1. 1H
NMR (500 MHz, CDCl3): δ 7.28−7.24 (m, 2H), 6.97−6.91 (m, 4H),
6.75 (dd, J1 = 7.2 Hz, J2 = 5.2 Hz, 2H), 6.44−6.37 (m, 2H), 6.25−
6.26 (m, 1H), 6.06−6.02 (m, 1H), 5.89 (dd, J1 = 9.3 Hz, J2 = 5.2 Hz,
1H), 5.68−5.65 (m, 1H), 3.40−3.34 (m, 2H), 3.33 (s, 3H), 3.31 (s,
3H), 3.29−3.22 (m, 2H). 13C{1H} NMR (125 MHz, CDCl3): δ
178.4, 177.9, 160.5, 159.6, 158.6, 157.5, 144.6, 144.4, 128.0, 127.9,
126.8, 126.3, 126.2, 126.1, 125.5, 122.7, 122.6, 122.2, 122.0, 121.9,
121.4, 121.1, 119.3, 119.2, 1183, 108.7, 107.9, 103.9, 103.8, 102.5,
102.3, 27.1, 26.9. HRMS (ESI) m/z: calcd for C15H12FNNaO [M +
Na]+ 264.0795, found 264.0797.
1′-Methyl-7′-(trifluoromethyl)spiro[bicyclo[4.1.0]heptane-7,3′-
indoline]-2,4-dien-2′-one (3o). Procedure A, red solid, 83% yield
1
(24.2 mg), Rf = 0.3 (EtOAc/petroleum ether 1:5). H NMR (400
MHz, CDCl3): δ 7.49 (d, J = 8.1 Hz, 1H), 6.95 (t, J = 7.9 Hz, 1H),
6.82 (d, J = 7.6 Hz, 1H), 6.52 (dd, J1 = 7.4 Hz, J2 = 2.8 Hz, 2H),
6.15−6.12 (m, 2H), 3.54 (d, J = 2.2 Hz, 3H), 3.28 (t, J = 2.9 Hz, 2H).
13C{1H} NMR (100 MHz, CDCl3): δ 179.9, 128.5, 126.8, 125.9,
124.0, 123.8, 123.7, 120.7, 112.1, 42.2, 29.8, 29.7, 13.9. HRMS (ESI)
m/z: calcd for C16H13F3NO [M + H]+ 292.0944, found 292.0945.
G
https://doi.org/10.1021/acs.joc.1c00418
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3-Chloro-1′-methylspiro[bicyclo[4.1.0]heptane-7,3′-indoline]-
2,4-dien-2′-one (3y). Procedure A, red solid, 74% yield (19.1 mg), Rf
135.4, 135.3, 132.6, 129.3, 129.0, 128.5, 128.3, 124.5, 122.4, 50.9,
30.1. HRMS (ESI) m/z: calcd for C15H13N2O3 [M + H]+ 269.0921,
found 269.0915.
1
= 0.3 (EtOAc/petroleum ether 1:5), regioisomer ratio 1:1. H NMR
(400 MHz, CDCl3): δ 7.26 (t, J = 7.6 Hz, 2H), 6.98−6.91 (m, 4H),
6.65 (dd, J1 = 13.4 Hz, J2 = 7.5 Hz, 2H), 6.53 (d, J = 6.5 Hz, 1H),
6.43−6.38 (m, 2H), 6.19−6.14 (m, 2H), 6.04 (dd, J1 = 9.3 Hz, J2 =
5.3 Hz, 1H), 3.34 (s, 3H), 3.32 (s, 3H), 3.28−3.19 (m, 4H). 13C{1H}
NMR (100 MHz, CDCl3): δ 178.0, 177.9, 144.7, 144.6, 131.1, 130.9,
128.7, 126.7, 126.6, 126.5, 126.1,125.6, 124.6, 123.0, 122.6, 122.4,
122.1, 122.0, 121.9, 120.4, 107.9, 107.8, 42.4, 42.0, 40.6, 40.3, 27.1,
27.0, 18.2, 15.5. HRMS (ESI) m/z: calcd for C15H13ClNO [M + H]+
258.0680, found 258.0679.
3-(4-Methoxyphenyl)-1-methylindolin-2-one (4z). Procedure A,
colorless oil, 77% yield (19.5 mg), Rf = 0.3 (EtOAc/petroleum ether
1:5), regioisomer ratio 1:1. 1H NMR (400 MHz, CDCl3): δ 7.32 (t, J
= 7.7 Hz, 1H), 7.29−7.24 (m, 2H), 7.16 (d, J = 7.3 Hz, 1H), 7.12 (d,
J = 7.9 Hz, 2H), 7.09−7.05 (m, 3H), 6.97 (t, J = 7.5 Hz, 1H), 6.93−
6.84 (m, 6H), 4.88 (s, 1H), 4.55 (s, 1H), 3.78 (s, 3H), 3.73 (s, 3H),
3.29 (s, 3H), 3.24 (s, 3H). 13C{1H} NMR (75 MHz, CDCl3): δ
176.9, 176.4, 159.1, 157.6, 144.5, 144.4, 130.1, 129.9, 129.6, 129.2,
129.0, 128.7, 128.4, 127.9, 126.1, 125.1, 124.2, 122.8, 122.5, 121.1,
114.4, 111.5, 108.2, 107.8, 55.9, 55.4, 51.3, 48.0, 26.6, 26.5. HRMS
(ESI) m/z: calcd for C16H16NO2 [M + H]+ 254.1176, found
254.1176.
1′-Methyl-1a,7b-dihydrospiro[cyclopropa[a]naphthalene-1,3′-
indolin]-2′-one (3aa). Procedure B, red solid, 40% yield (10.9 mg),
Rf = 0.3 (EtOAc/petroleum ether 1:5). 1H NMR (400 MHz, CDCl3):
δ 7.35−7.29 (m, 3H), 7.26−7.22 (m, 2H), 7.15 (t, J = 7.7 Hz, 1H),
6.89−6.86 (m, 2H), 6.72 (t, J = 7.8 Hz, 1H), 6.27 (d, J = 7.6 Hz, 1H),
6.11 (dd, J1 = 9.5 Hz, J2 = 5.2 Hz, 1H), 3.66 (d, J = 8.6 Hz, 1H), 3.34
(s, 3H), 3.22 (dd, J1 = 8.7 Hz, J2 = 5.3 Hz, 1H). 13C{1H} NMR (125
MHz, CDCl3): δ 178.4, 144.6, 132.6, 130.5, 129.6, 129.4, 128.7,
128.0, 127.9, 126.4, 124.9, 122.4, 122.0, 121.7, 107.8, 37.6, 36.7, 27.0,
21.6. HRMS (ESI) m/z: calcd for C19H16NO [M + H]+ 274.1226,
found 274.1229.
3-(4-(tert-Butyl)phenyl)-1-methylindolin-2-one (4w). Colorless
oil, 73% yield (72 h, 20.4 mg), Rf = 0.3 (EtOAc/petroleum ether
1:5), regioisomer ratio 3:3:1. 1H NMR (400 MHz, CDCl3): δ 7.46 (d,
J = 8.0 Hz, 1H), 7.35−7.28 (m, 5.2H), 7.19−7.12 (m, 4.5 H), 7.07−
6.99 (m, 4.3H), 6.90 (dd, J1 = 11.1 Hz, J2 = 7.9 Hz, 2.6H), 6.52 (d, J =
7.6 Hz, 1H), 5.42 (s, 1H), 4.61 (s, 0.3H), 4.58 (s, 1H), 3.29 (s, 3H),
3.25 (s, 1H), 3.24 (s, 3H), 1.59 (s, 9H), 1.30 (s, 3H), 1.29 (s, 9H).
13C{1H} NMR (75 MHz, CDCl3): δ 177.1, 176.3, 176.2, 151.7, 150.4,
148.9, 144.6, 144.5, 136.3, 136.2, 133.5, 131.9, 130.2, 129.0, 128.6,
128.4, 128.2, 128.1, 127.3, 126.8, 126.5, 126.3, 125.9, 125.2, 125.2,
125.1, 124.7, 124.6, 122.9, 122.8, 108.2, 108.1, 107.6, 60.5, 52.3, 51.6,
49.7, 35.4, 34.8, 34.6, 32.4, 31.5, 31.4, 29,8, 26.5, 21.2, 14.3. HRMS
(ESI) m/z: calcd for C19H22NO [M + H]+ 280.1696, found 280.1695.
Procedure for the Monoepoxidation of Norcaradiene 3a. A
dram vial was charged with m-CPBA (27 mg, 0.12 mmol, 1.2 equiv),
KF (7 mg, 0.12 mmol, 1.2 equiv), and CH2Cl2 (500 μL). The
resulting mixture was stirred for 20 min before adding 3a (23 mg, 0.1
mmol) as a solution in 1 mL of CH2Cl2. The reaction mixture was
stirred at ambient temperature for 59 h. Then, the reaction mixture
was concentrated in vacuo. The residue was purified by flash column
chromatography (eluted with EtOAc/petroleum ether 1:5) to afford
the product 5a.
1-Methyl-8′-oxaspiro[indoline-3,3′-tricyclo[5.1.0.02,4]octan]-5′-
en-2-on (5a). Red solid, 52% yield (12.4 mg), Rf = 0.4 (EtOAc/
petroleum ether 1:5). 1H NMR (400 MHz, CDCl3): δ 7.32 (t, J = 7.7
Hz, 1H), 7.12 (d, J = 7.5 Hz, 1H), 7.01 (t, J = 7.6 Hz, 1H), 6.95 (d, J
= 7.8 Hz, 1H), 6.16 (dd, J1 = 9.6 Hz, J2 = 3.7 Hz, 1H), 5.85 (dd, J1 =
9.5 Hz, J2 = 4.6, 1H), 3.49 (d, J = 2.5 Hz, 1H), 3.35 (s, 1H), 3.29 (s,
3H). 13C{1H} NMR (75 MHz, CDCl3): δ 174.6, 144.7, 128.0, 127.5,
124.9, 124.5, 122.4, 121.8, 108.5, 51.5, 47.9, 37.8, 29.8, 29.4, 26.8.
HRMS (ESI) m/z: calcd for C15H14NO2 [M + H]+ 240.1019, found
240.1016.
1-Methyl-3-(1-methyl-1H-pyrrol-2-yl)indolin-2-one (4ac). Proce-
dure B, colorless oil, 18% yield (4.1 mg), Rf = 0.4 (EtOAc/petroleum
ether 1:5). 1H NMR (400 MHz, CDCl3): δ 7.33 (t, J = 7.7 Hz, 1H),
7.27 (d, J = 7.5 Hz, 1H), 7.08 (t, J = 7.5 Hz, 1H), 6.87 (d, J = 7.8 Hz,
1H), 6.63 (t, J = 2.1 Hz, 1H), 6.03 (t, J = 3.1 Hz, 1H), 5.78−5.77 (m,
1H), 4.74 (s, 1H), 3.69 (s, 3H), 3.22 (s, 3H). 13C{1H} NMR (75
MHz, CDCl3): δ 175.0, 144.4, 128.6, 127.6, 126.6, 125.2, 123.7,
122.9, 108.5, 108.3, 107.0, 44.8, 34.6, 26.5. HRMS (ESI) m/z: calcd
for C14H15N2O [M + H]+ 227.1179, found 227.1181.
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.joc.1c00418.
■
sı
Copies of NMR spectra and crystal data (PDF)
Accession Codes
General Procedure for Silica Gel-Promoted Ring Opening
of Norcaradiene 3. Silica gel (160−200 mesh, 40 mg) was added
into a solution of norcaradiene 3 (0.1 mmol) in CHCl3 (2 mL). The
mixture was heated to 50 °C (oil bath) for specific time. Then, the
mixture was filtered and concentrated to give product 4 in a pure
form.
CCDC 2052276 contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge
via www.ccdc.cam.ac.uk/data_request/cif, or by emailing
data_request@ccdc.cam.ac.uk, or by contacting The Cam-
bridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
1-Methyl-3-phenylindolin-2-one (4a). Red solid, quantitative yield
1
(29 h, 22.3 mg), Rf = 0.3 (EtOAc/petroleum ether 1:5). H NMR
(400 MHz, CDCl3): δ 7.34−7.24 (m, 4H), 7.21−7.05 (m, 3H), 7.05
(t, J = 7.4 Hz, 1H), 6.85 (d, J = 7.8 Hz, 1H), 4.60 (s, 1H), 3.24 (s,
3H). 13C{1H} NMR (75 MHz, CDCl3): δ 176.1, 144.6, 136.7, 129.0,
128.9, 128.5, 127.6, 125.1, 122.8, 108.3, 52.1, 26.6. HRMS (ESI) m/z:
calcd for C15H14NO [M + H]+ 224.1070, found 224.1069.
AUTHOR INFORMATION
Corresponding Author
■
Xin Chen − School of Pharmacy, Changzhou University,
Changzhou, Jiangsu 213164, China; orcid.org/0000-
0002-5189-5647; Email: xinchen@cczu.edu.cn
6-Chloro-1-methyl-3-phenylindolin-2-one (4j). Colorless oil, 59%
1
yield (72 h, 15.2 mg), Rf = 0.4 (EtOAc/petroleum ether 1:5). H
Authors
NMR (400 MHz, CDCl3): δ 7.36−7.26 (m, 3H), 7.17 (d, J = 6.8 Hz,
2H), 7.09−7.03 (m, 2H), 6.90 (d, J = 1.3 Hz, 1H), 4.57 (s, 1H), 3.23
(s, 3H). 13C{1H} NMR (75 MHz, CDCl3): δ 176.03, 145.8, 136.1,
134.3, 129.1, 128.5, 127.9, 127.2, 126.1, 122.7, 109.0, 51.7, 26.7.
HRMS (ESI) m/z: calcd for C15H13ClNO [M + H]+ 258.0680, found
258.0678.
Shuai Zhao − School of Pharmacy, Changzhou University,
Changzhou, Jiangsu 213164, China
Xiang-Xiang Chen − School of Pharmacy, Changzhou
University, Changzhou, Jiangsu 213164, China
Nan Gao − School of Pharmacy, Changzhou University,
Changzhou, Jiangsu 213164, China
1-Methyl-7-nitro-3-phenylindolin-2-one (4n). Colorless oil, 82%
1
yield (12 h, 22.0 mg), Rf = 0.3 (EtOAc/petroleum ether 1:5). H
Mingcheng Qian − School of Pharmacy, Changzhou
University, Changzhou, Jiangsu 213164, China
NMR (400 MHz, CDCl3): δ 7.71 (d, J = 8.3 Hz, 1H), 7.38−7.30 (m,
4H), 7.17 (d, J = 6.6 Hz, 2H), 7.11 (t, J = 7.9 Hz, 1H), 4.65 (s, 1H),
3.28 (s, 3H). 13C{1H} NMR (75 MHz, CDCl3): δ 176.5, 138.0,
Complete contact information is available at:
H
https://doi.org/10.1021/acs.joc.1c00418
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
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https://pubs.acs.org/10.1021/acs.joc.1c00418
Author Contributions
‡These authors contributed equally.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We gratefully acknowledge the financial support from the
National Natural Science Foundation of China (21602018 and
22077012) and the Postgraduate Research & Practice
Innovation Program of Jiangsu Province.
(5) (a) Buchner, E.; Curtius, T. Ueber die Einwirkung von
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