Synthesis of N-Fused Seven-Membered Indoline-3-ones via a Palladium-Catalyzed One-Pot Insertion Reaction from 2-Alkynyl Arylazides and Cyclic β-Diketones

Article abstract of DOI:10.1002/ejoc.202000243

A novel strategy to synthesize N-fused seven-membered multifunctional polycyclic indoline-3-one derivatives via insertion of cyclic C-acylimines into cyclic β-diketones has been described. The reaction proceeded well under mild reaction conditions via a one-pot, three-steps method, which has shown good tolerance of various functional groups.

Full text of DOI:10.1002/ejoc.202000243

A Journal of
Accepted Article
Title: Synthesis of N-fused Seven-Membered Indoline-3-ones via
Palladium-Catalyzed One-Pot Insertion Reaction from 2-Alkynyl
Arylazides and Cyclic β-diketones
Authors: Ping Li, Rong Sheng, Zhiqiang Zhou, Guiwen Hu, and
Xiaoxiang Zhang
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10.1002/ejoc.202000243
European Journal of Organic Chemistry
FULL PAPER
Synthesis of N-fused Seven-Membered Indoline-3-ones via
Palladium-Catalyzed One-Pot Insertion Reaction from 2-Alkynyl
Arylazides and Cyclic β-diketones
Ping Li,[a] Rong Sheng,[a] Zhiqiang Zhou,[a] Guiwen Hu,[a] and Xiaoxiang Zhang*[a]
[a]
P. Li, R. Sheng, Z. Zhou, G. Hu, Prof. Dr . X. Zhang
Jiangsu key lab of Biomass-based Green Fuels and Chemicals, College of Chemical Engineering,
Nanjing Forestry University
Nanjing 210037, China
E-mail: zhangxiaoxiang@njfu.edu.cn
Supporting information for this article is given via a link at the end of the document.((Please delete this text if not appropriate))
Abstract: A novel strategy to synthesize N-fused seven-membered
multifunctional polycyclic indoline-3-one derivatives via insertion synthesis of N-fused five- or six-membered indoline-3-ones have
reaction of cyclic C-acylimines into cyclic β -diketones has been been reported, the preparation of N-fused seven-membered
respectively [Scheme 1, (4)]. However, the methods for the
described. The reaction was proceeded well under mild reaction indoline-3-ones has not been studied. Thus, studies on
conditions via one-pot three steps method, which has shown good synthesis of N-fused seven-membered indoline-3-ones have
tolerance of various functional groups.
great necessary.
Recently, the insertion of unsaturated bonds into carbon-
carbon σ-bonds provided an efficient strategy to synthesize
polyfunctional molecules 11. Especially, the cyclic β-diketones
were employed as the key substrates to construct the medium-
Introduction
size ring in various insertion reactions 12. On the basis of
Indolin-3-ones with a N-fused ring as an important kind of
heterocycles have unique biological and pharmaceutical
activities which exist as core scaffold in a number of natural
products 1, such as (-)-isatisine A 2, (-)-melokhanine E
fluorocarpamine
synthesis of indolin-3-ones containing a N-fused ring have been
11-12
previous studies
as well as our ongoing efforts on synthesis
of various indolin-3-ones 13, we envisaged that the N-fused
seven-membered indoline-3-ones could be obtained through
Palladium-catalyzed one-pot insertion reaction of 3H-indol-3-
ones into cyclic β-diketones from 2-alkynyl arylazides [Scheme 1,
(5)].
3
,
4
(Figure 1). Thus, the methods for the
Figure 1. Representative natural products containing N-fused indoline-3-ones.
reported extensively 5. Among those reported reactions, the
6
substituted 2-aryl-3H-indol-3-ones G were used as the key
substrates, which could be attacked easily by various
7
nucleophilic reagents. Recently, Fu’s group demonstrated a
synthetic strategy of imidazo[1,5-a]indol-3-ones by chiral
phosphoric acid catalyzed sequential additions of G, aldehydes
and diethyl 2-aminomalonate [Scheme 1, (1)]. Later, an NHC-
catalyzed [4 + 2] annulation reaction of G with α,β-unsaturated
carboxylic acids to produce N-fused six-membered indoline-3-
8
ones has been developed by Du’s group [Scheme 1, (2)]. In
9
2012, Lavilla and co-workers
reported a method for the
synthesis of dihydropyrimido[1,6-a]indoline-3-ones through
multicomponent reaction between dihydropyran, nitrile and G
with Sc(OTf)3 catalysis [Scheme 1, (3)]. Besides, three different
aza-Diels-Alder cycloaddition methods to generate a series of N-
fused six-membered indoline-3-ones have been described by
Scheme 1. Synthesis of N-fused indoline-3-ones.
10b
10c
Raja’s group 10a, Luque’s group
and Chen’s group
,
1
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10.1002/ejoc.202000243
European Journal of Organic Chemistry
FULL PAPER
Results and Discussion
were investigated (entries 4-7). However, switching Cs2CO3
to K2CO3 was found to result in long reaction time and low
product yield (entry 4). When K3PO4 was used as a base,
the desired product 4a was obtained in 22% yield due to the
Based on our previous work 13, the reaction conditions were
optimized
in
Table
1.
Initially,
the
1-azido-2-
low intermediate conversion of
E to G (entry 5). When
(phenylethynyl)benzene 1a (0.1 mmol) was chosen as a model
substrate under the conditions of Pd(OAc)2 (5 mol%), TsOH (3
equiv) in 1,4-dioxane (1 mL) at room temperature for 10 min to
strong base t-BuOK and organic base DBU were employed,
the desired product was obtained in yields of 19-33%. In
these reactions, many byproducts were detected by TLC
analysis (entries 6-7). The desired product 4a could not be
detected without any base (entry 8). When the amount of
Cs2CO3 was decreased to 2.5 equiv, the desired product 4a
was also obtained in 73% yield after long reaction time
(entry 9).
form
the
intermediate
2-phenyl-1H-indol-3-yl
4-
methylbenzenesulfonate E. Then Cs2CO3 (3.5 equiv) and ethyl
2-oxocyclopentane-1-carboxylate 3a (1.5 equiv) were added into
the reaction, which was stirred at 90 ℃ for 5 h. The desired
product
trans-ethyl
6,11-dioxo-10a-phenyl-7,8,9,10,10a,11-
hexahydro-6H-azepino[1,2-a]indole-10-carboxylate
4a was
With the optimal reaction conditions in hand, we began to
evaluate the generality of this method with a variety of 2-alkynyl
arylazides 1 and cyclic β-diketones 3. As shown in Table 2, 2-
obtained in 81% yield (entry 1). The structure of product 4a was
confirmed by the analysis of H NMR and determination of X-ray
crystal structure (Figure 2).
1
alkynyl arylazides
1 containing an electron-withdrawing or
Subsequently, the reaction was found to accomplish in
0.7 h by adding 3a after the formation of intermediate 2-
electron-donating group on the aromatic ring could be reacted
with ethyl 2-oxocyclopentane-1-carboxylate 3a to produce
corresponding compounds in moderate to good yields of 52-81%
(4a, 4c-4j). When the substituted group CF3 was on the aromatic
ring, the desired product 4k was afforded in slightly low yield of
52%. Substrates with different substituted aryl or hetero aryl
groups on the terminal alkyne carbon were also suitable for the
insertion reaction, which gave the desired products 4l, 4n-4p,
4r-4s and 4u in the yields of 62-77%. However, the yield of 4t
was decreased to 45%. Substrates bearing aliphatic pendant
groups were also examined and provided the desired product 4v
and 4w in yields of 55% and 45%, respectively. In contrast,
substrate with R2 = t-butyl group 1x was failed to the reaction
phenyl-3H-indol-3-one
G, which also provided the desired
product 4a in 81% yield (entry 2). Therefore, all the
reactions were carried out in three steps. When the reaction
was conducted at 60
℃, it took longer time and generated
lower yield of 63% (entry 3). Afterwards, various bases
Table 1. Optimization of the reaction conditions. [a]
and only the first-step intermediate 2-(tert-butyl)-1H-indol-3-yl 4-
13b
Entry
Base
Cs2CO3
Cs2CO3
Cs2CO3
K2CO3
K3PO4
t-BuOK
DBU
T (℃)
90
90
60
90
90
90
90
90
Time (h)
5.0
Yield/%[b]
methylbenzenesulfonate
could be isolated, which was
81[c]
81
probably due to the steric hindrance. Likewise, methyl 2-
oxocyclopentane-1-carboxylate 3b was also proved to be a good
substrate for the insertion reaction to construct N-fused seven-
membered indoline-3-ones (4b, 4m and 4q). Furthermore, the
desired products 4h-4i, 4k and 4v-4w were obtained using two-
step method, which was probably due to the unstability of 3H-
indol-3-ones with strong electron-withdrawing group on the
aromatic ring or aliphatic group on the terminal alkyne carbon.
Under the standard reaction conditions, 1H-indene-1,3(2H)-
dione 3c was next explored for the insertion reaction (Table 3).
However, no desired insertion product was obtained. The
intermolecular addition intermediate 5a was isolated in 44%
yield. When the substituted group R2 was changed from Ph to n-
butyl, the reacion was still afforded the intermediate 5b in 40%
1
2
3
4
5
6
7
8
9
0.7
4.5
2.5
28
1.5
4.0
28
4.5
63
69
22
33
19
----
Cs2CO3
n.r.[d][ e]
73f
90
[a] Reaction conditions: 1a (0.1 mmol), Pd(OAc)2 (5 mol%), 2a (3 equiv), 1,4-
dioxane (1 mL), base (3.5 equiv), and 3a (1.5 equiv) was added after the
formation of 2-phenyl-3H-indol-3-one G. [b] Isolated yield. [c] Cs2CO3 and 3a
were added in the same time after the first step. [d] Without base. [e] No
desired product was detected. [f] 2.5 equiv of Cs2CO3 was used.
yield after 8 h.
13
According to our previous research
and above
experiment results, we proposed a plausible mechanism for the
synthesis of N-fused seven-membered indolin-3-ones in scheme
2. At the outset, the triple bond of 1a was activated by Palladium
catalyst and delivered the complex A. Intramolecular cyclization
of azide group to the activated alkyne led to the formation of
14
complex B. Then the α-imino palladium carbene C generated
in situ by releasing the N2 could be trapped by TsOH to afford
the complex D, which followed by protodemetalation to form 1H-
indole-3-sulfonate E 13b. Basic conditions produce the 2-phenyl-
15
16
3H-indol-3-one G via 1,3-Ts shift of E and further reductive
desulfonation
17
6-10
of α-amino sulfone F. Nucleophilic addition
of 3a to G afforded the complex H, which resulted in a four-
membered ring complex I after intramolecular addition 11. Finally,
Figure 2. ORTEP drawing of 4a with thermal ellipsoids at 50% probability.
2
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10.1002/ejoc.202000243
European Journal of Organic Chemistry
FULL PAPER
the desired product 4aa was obtained by protonation of complex
Table 3. Reactions of 1H-indene-1,3(2H)-dione 3c.[a] [b]
J, which was generated from the ring expansion of I 12
.
Table 2. Exploration of Substrate Scope. [a] [b]
[a] Reaction conditions: 1a (0.1 mmol), Pd(OAc)2 (5 mol%), TsOH (3 equiv),
1,4-dioxane (1 mL), Cs2CO3 (3.5 equiv), and 3c (1.5 equiv) was added after
the formation of 3H-indol-3-ones. [b] Isolated yield. [c] Cs2CO3 and 3c were
added in the same time after the first step.
Scheme 2. A plausible reaction mechanism.
Conclusion
In conclusion, we have disclosed a novel insertion reaction from
2-alkynyl arylazides and cyclic β-diketones in one-pot three
steps. The corresponding N-fused seven-membered indoline-3-
ones were obtained in moderate to good yields under mild
reaction conditions. The results indicate that the reaction can
tolerate various functional groups. Further applications of this
strategy are currently underway and will be reported in future.
Experimental Section
General experimental procedure for the synthesis of 4/5a in three
steps: To a 10 mL of flask was added 2-alkynyl arylazides 1 (0.1 mmol,
1 equiv), TsOH 2 (0.3 mmol, 3 equiv), Pd(OAc)2 (5 mol%), and 1,4-
dioxane (1 mL). The reaction mixture was stirred at room temperature.
After the 2-alkynyl arylazides 1 disappeared monitored by TLC, Cs2CO3
(0.35 mmol, 3.5 equiv) was added to the reaction solution, which was
then stirred at 90 ℃ . When 3H-indol-3-one was completely formed, 3
[a] Reaction conditions: 1a (0.1 mmol), Pd(OAc)2 (5 mol%), TsOH (3 equiv),
1,4-dioxane (1 mL), Cs2CO3 (3.5 equiv), and 3 (1.5 equiv) was added after the
formation of 3H-indol-3-ones. [b] Isolated yield. [c] Cs2CO3 and 3a were added
in the same time after the first step. [d] The first-step product 2-(tert-butyl)-1H-
indol-3-yl 4-methylbenzenesulfonate was isolated.
3
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10.1002/ejoc.202000243
European Journal of Organic Chemistry
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(0.15 mmol, 1.5 equiv) was added into the above mixture at 90 ℃. On
completion monitored by TLC, the reaction mixture was directly subjected
to purification by flash column chromatography on silica gel to give the
desired 4. (eluent: petrol ether: ethyl acetate = 40:1 to 8:1).
yield = 58%; yellow solid; m.p. 158.8-160.2 ℃ ; 1H NMR (CDCl3, 600
MHz): δ = 0.98 (t, J = 7.2 Hz, 3 H), 1.67-1.71 (m, 2 H), 1.79-1.85 (m, 1 H),
2.32 (s, 3 H), 2.37 (s, 3 H), 2.39-2.44 (m, 2 H), 2.63-2.66 (m, 1 H), 3.97-
4.04 (m, 2 H), 4.33 (t, J = 4.2 Hz, 1 H), 7.26-7.28 (m, 1 H), 7.32-7.35 (m,
4 H), 7.43 (d, J = 7.8 Hz, 2 H); 13C NMR (CDCl3, 150 MHz): δ = 12.8,
19.8, 20.1, 20.9, 25.2, 37.4, 48.7, 60.6, 74.3, 120.9, 124.1, 125.1, 127.4,
128.0, 128.5, 134.1, 134.7, 139.3, 150.0, 169.7, 171.1, 197.0; HRMS
(ESI) calcd for C24H26NO4 [M+H]+ 392.1862, found 392.1868.
General experimental procedure for the synthesis of 4/5b in two
steps: To a 10 mL of flask was added 2-alkynyl arylazides 1 (bearing
strong electron-withdrawing group on the aromatic ring or aliphatic group
on the terminal alkyne carbon) (0.1 mmol, 1 equiv), TsOH 2 (0.3 mmol, 3
equiv), Pd(OAc)2 (5 mol%), and 1,4-dioxane (1 mL). The reaction mixture
trans-Ethyl
hexahydro-6H-azepino[1,2-a] indole-10-carboxylate (4f): Isolated
disappeared, Cs2CO3 (0.35 mmol, 3.5 equiv) and 3 (0.15 mmol, 1.5 equiv) yield = 66%; yellow solid; m.p. 152.9-153.8 ℃ ; 1H NMR (CDCl3, 600
2-chloro-6,11-dioxo-10a-phenyl-7,8,9,10,10a,11-
was stirred at room temperature. After the 2-alkynyl arylazides
1
were added to the reaction solution together, which was then stirred at
90 ℃ and monitored by TLC analysis. On completion, the reaction
mixture was directly subjected to purification by flash column
chromatography on silica gel to give the desired 4. (eluent: petrol ether:
ethyl acetate = 40:1 to 8:1).
MHz): δ = 0.99 (t, J = 7.2 Hz, 3 H), 1.73-1.77 (m, 2 H), 1.95-2.01 (m, 1 H),
2.26-2.31 (m, 1 H), 2.46-2.49 (m, 1 H), 2.60-2.64 (m, 1 H), 3.97-4.03 (m,
2 H), 4.30 (t, J = 4.2 Hz, 1 H), 7.25-7.28 (m, 2 H), 7.30-7.33 (m, 1 H),
7.36-7.38 (m, 2 H), 7.63-7.64 (m, 2 H), 8.77 (d, J = 9.6 Hz, 1 H); 13C
NMR (CDCl3, 150 MHz): δ = 12.8, 19.9, 25.4, 38.4, 47.9, 60.7, 74.1,
119.0, 123.2, 123.3, 127.5, 127.8, 128.9, 129.3, 135.6, 151.0, 169.5,
172.6, 194.6; HRMS (ESI) calcd for C22H21ClNO4 [M+H]+ 398.1159, found
398.1164.
trans-Ethyl
6,11-dioxo-10a-phenyl-7,8,9,10,10a,11-hexahydro-6H-
azepino[1,2-a]indole-10- carboxylate (4a): Isolated yield = 81%; yellow
solid; m.p. 133.3-134.2 ℃; 1H NMR (CDCl3, 600 MHz): δ = 0.88 (t, J =
6.6 Hz, 3 H), 1.71-1.83 (m, 2 H), 1.97-2.03 (m, 1 H), 2.28-2.33 (m, 1 H),
2.44-2.47 (m, 1 H), 2.59-2.63 (m, 1 H), 3.92-3.98 (m, 2 H), 4.30 (t, J = 4.2
Hz, 1 H), 7.22-7.31 (m, 4 H), 7.34-7.37 (m, 2 H), 7.68-7.71 (m, 2 H), 8.80
(d, J = 8.4 Hz, 1 H); 13C NMR (CDCl3, 150 MHz): δ = 12.6, 19.9, 25.4,
38.5, 47.6, 60.5, 73.6, 117.8, 121.7, 123.7, 123.8, 127.5, 128.8, 134.0,
135.9, 152.7, 169.4, 172.7, 195.7; HRMS (ESI) calcd for C22H22NO4
[M+H]+ 364.1549, found 364.1555.
trans-Ethyl
2-fluoro-6,11-dioxo-10a-phenyl-7,8,9,10,10a,11-
hexahydro-6H-azepino[1,2-a] indole-10-carboxylate (4g): Isolated
yield = 69%; yellow solid; m.p. 136.3-137.3 ℃ ; 1H NMR (CDCl3, 600
MHz): δ = 0.97 (t, J = 7.2 Hz, 3 H), 1.73-1.82 (m, 2 H), 1.96-2.02 (m, 1 H),
2.26-2.31 (m, 1 H), 2.45-2.48 (m, 1 H), 2.60-2.64 (m, 1 H), 3.97-4.01 (m,
2 H), 4.29 (t, J = 3.6 Hz, 1 H), 7.26-7.29 (m, 2 H), 7.31-7.33 (m, 2 H),
7.36-7.42 (m, 3 H), 8.81-8.83 (dd, J1 = 9.6 Hz, J2 = 4.2 Hz, 1 H); 13C
NMR (CDCl3, 150 MHz): δ = 12.8, 19.9, 25.5, 38.4, 48.0, 60.6, 74.2,
109.1 (d, J = 22.9 Hz), 119.4 (d, J = 6.9 Hz), 122.9, 123.0, 123.3 (d, J =
7.7 Hz), 127.7, 128.9, 133.8, 149.1, 158.6 (d, J = 245.1 Hz), 169.4, 172.4,
194.9; HRMS (ESI) calcd for C22H21FNO4 [M+H]+ 382.1455, found
382.1459.
trans-Methyl
6,11-dioxo-10a-phenyl-7,8,9,10,10a,11-hexahydro-6H-
azepino[1,2-a]indole-10- carboxylate (4b): Isolated yield = 79%; yellow
solid; m.p. 185.6-186.3 ℃; 1H NMR (CDCl3, 600 MHz): δ = 1.71-1.82 (m,
2 H), 1.99-2.05 (m, 1 H), 2.28-2.33 (m, 1 H), 2.43-2.46 (dd, J1 = 14.4 Hz,
J2 = 3.6 Hz, 1 H), 2.60-2.64 (dd, J1 = 14.4 Hz, J2 = 6.6 Hz, 1 H), 3.51 (s, 3
H), 4.33 (t, J = 4.2 Hz, 1 H), 7.22-7.24 (m, 1 H), 7.27-7.31 (m, 3 H), 7.35-
7.37 (m, 2 H), 7.69-7.72 (m, 2 H), 8.81 (d, J = 8.4 Hz, 1 H); 13C NMR
(CDCl3, 150 MHz): δ = 20.1, 25.4, 38.5, 47.8, 51.4, 73.6, 117.8, 121.6,
123.7, 123.9, 127.6, 1288, 133.9, 136.0, 152.6, 170.1, 172.7, 195.8;
HRMS (ESI) calcd for C21H20NO4 [M+H]+ 350.1392, found 350.1397.
trans-Ethyl
7,8,9,10,10a,11-hexahydro-6H-
6,11-dioxo-10a-phenyl-2-(trifluoromethyl)-
azepino[1,2-a]indole-10-carboxylate
(4h): Isolated yield = 67%; yellow solid; m.p. 160.7-161.4 ℃ ; 1H NMR
(CDCl3, 600 MHz): δ = 0.98 (t, J = 7.2 Hz, 3 H), 1.74-1.78 (m, 2 H), 1.97-
2.03 (m, 1 H), 2.29-2.34 (m, 1 H), 2.48-2.51 (m, 1 H), 2.63-2.67 (m, 1 H),
3.98-4.02 (m, 2 H), 4.34 (t, J = 4.2 Hz, 1 H), 7.26-7.29 (m, 2 H), 7.29-7.34
(m, 1 H), 7.37-7.39 (m, 2 H), 7.92-7.95 (m, 2 H), 8.93 (d, J = 8.4 Hz, 1 H);
13C NMR (CDCl3, 150 MHz): δ = 13.4, 20.6, 25.9, 39.0, 48.7, 61.4, 74.9,
118.7, 121.8 (d, J = 3.7 Hz), 122.6, 124.9 (d, J = 185.4 Hz), 126.6 (d, J =
33.3 Hz), 128.5, 129.6, 133.2 (d, J = 3.3 Hz), 133.9, 155.0, 170.1, 173.6,
195.3; HRMS (ESI) calcd for C23H21F3NO4 [M+H]+ 432.1423, found
432.1428.
trans-Ethyl
2-methyl-6,11-dioxo-10a-phenyl-7,8,9,10,10a,11-
hexahydro-6H-azepino[1,2-a] indole-10-carboxylate (4c): Isolated
yield = 70%; yellow solid; m.p. 138.7-139.8 ℃ ; 1H NMR (CDCl3, 600
MHz): δ = 0.93 (t, J = 6.6 Hz, 3 H), 1.70-1.82 (m, 2 H), 1.96-2.02 (m, 1 H),
2.26-2.31 (m, 1 H), 2.37 (s, 3 H), 2.44-2.47 (m, 1 H), 2.58-2.62 (m, 1 H),
3.94-3.99 (m, 2 H), 4.29 (t, J = 3.6 Hz, 1 H), 7.26-7.30 (m, 3 H), 7.34-7.36
(m, 2 H), 7.47 (s, 1 H), 7.51-7.52 (dd, J1 = 9 Hz, J2 = 1.8 Hz, 1 H), 8.68 (d,
J = 8.4 Hz, 1 H); 13C NMR (CDCl3, 150 MHz): δ = 12.7, 19.9, 20.0, 25.4,
38.4, 47.7, 60.5, 73.8, 117.6, 121.8, 123.4, 127.5, 128.7, 133.8, 134.2,
137.1, 150.8, 169.5, 172.5, 195.7; HRMS (ESI) calcd for C23H24NO4
[M+H]+ 378.1705, found 378.1710.
trans-10-Ethyl
2-methyl
6,11-dioxo-10a-phenyl-7,8,9,10,10a,11-
hexahydro-6H-azepino[1,2-a] indole-2,10-dicarboxylate (4i): Isolated
yield = 79%; white solid; m.p. 178.3-190.0 ℃; 1H NMR (CDCl3, 600 MHz):
δ = 0.94 (t, J = 7.2 Hz, 3 H), 1.74-1.78 (m, 2 H), 1.98-2.02 (m, 1 H), 2.28-
2.33 (m, 1 H), 2.46-2.49 (m, 1 H), 2.61-2.65 (m, 1 H), 3.90 (s, 3 H), 3.94-
4.00 (m, 2 H), 4.32 (t, J = 3.6 Hz, 1 H), 7.17-7.26 (m, 2 H), 7.29-7.32 (m,
1 H), 7.35-7.38 (m, 2 H), 8.35-8.38 (m, 2 H), 8.85 (d, J = 8.4 Hz, 1 H); 13C
NMR (CDCl3, 150 MHz): δ = 12.8, 19.9, 25.3, 38.4, 47.8, 51.4, 60.7, 74.3,
117.4, 121.9, 125.6, 125.7, 127.8, 128.9, 133.5, 137.1, 155.3, 164.9,
169.4, 172.9, 194.8; HRMS (ESI) calcd for C24H24NO6 [M+H]+ 422.1604,
found 422.1608.
trans-Ethyl
3-methyl-6,11-dioxo-10a-phenyl-7,8,9,10,10a,11-
hexahydro-6H-azepino[1,2-a] indole-10-carboxylate (4d): Isolated
yield = 67%; yellow solid; m.p. 139.8-140.7 ℃ ; 1H NMR (CDCl3, 600
MHz): δ = 0.92 (t, J = 7.2 Hz, 3 H), 1.71-1.83 (m, 2 H), 1.97-2.03 (m, 1 H),
2.27-2.32 (m, 1 H), 2.43-2.46 (m, 1 H), 2.51 (s, 3 H), 2.58-2.62 (m, 1 H),
3.94-3.98 (m, 2 H), 4.28 (t, J = 3.6 Hz, 1 H), 7.05 (d, J = 7.8 Hz, 1 H),
7.26-7.30 (m, 3 H), 7.34-7.36 (m, 2 H), 7.57 (d, J = 7.8 Hz, 1 H), 8.65 (s,
1 H); 13C NMR (CDCl3, 150 MHz): δ = 12.7, 20.0, 22.0, 25.4, 38.5, 47.4,
60.5, 73.8, 118.1, 119.5, 123.5, 125.2, 127.4, 128.7, 134.3, 147.8, 153.0,
169.5, 172.8, 195.1; HRMS (ESI) calcd for C23H24NO4 [M+H]+ 378.1705,
found 378.1708.
trans-Ethyl
3-chloro-6,11-dioxo-10a-phenyl-7,8,9,10,10a,11-
hexahydro-6H-azepino[1,2-a] indole-10-carboxylate (4j): Isolated yield
= 63%; yellow solid; m.p. 130.8-131.6 ℃; 1H NMR (CDCl3, 600 MHz): δ =
0.98 (t, J = 7.2 Hz, 3 H), 1.73-1.77 (m, 2 H), 1.96-2.02 (m, 1 H), 2.26-2.32
(m, 1 H), 2.45-2.48 (m, 1 H), 2.60-2.64 (m, 1 H), 3.98-4.01 (m, 2 H), 4.29
(t, J = 4.2 Hz, 1 H), 7.21-7.22 (dd, J1 = 8.4 Hz, J2 = 1.8 Hz, 1 H), 7.26-
7.28 (m, 2 H), 7.30-7.33 (m, 1 H), 7.36-7.37 (m, 2 H), 7.61 (d, J = 7.8 Hz,
1 H), 8.87 (d, J = 1.2 Hz, 1 H); 13C NMR (CDCl3, 150 MHz): δ = 12.8,
19.9, 25.4, 38.4, 47.8, 60.7, 74.1, 118.2, 120.2, 124.53, 127.7, 128.9,
trans-Ethyl
2,4-dimethyl-6,11-dioxo-10a-phenyl-7,8,9,10,10a,11-
hexahydro-6H-azepino[1,2-a] indole-10-carboxylate (4e): Isolated
4
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10.1002/ejoc.202000243
European Journal of Organic Chemistry
FULL PAPER
133.7, 142.4, 153.0, 169.5, 172.8, 194.5; HRMS (ESI) calcd for
C22H21ClNO4 [M+H]+ 398.1159, found 398.1163.
7.68-7.72 (m, 2 H), 8.78 (d, J = 9 Hz, 1 H); 13C NMR (CDCl3, 150 MHz): δ
= 12.6, 19.9, 25.4, 38.5, 47.6, 60.7, 73.2, 117.9, 121.5, 123.8, 124.0,
128.9, 132.7, 133.8, 136.2, 152.6, 169.2, 172.5, 195.3; HRMS (ESI)
calcd for C22H21ClNO4 [M+H]+ 398.1159, found 398.1164.
trans-Ethyl
6,11-dioxo-10a-phenyl-3-(trifluoromethyl)-
[1,2-a]indole-10-carboxylate
7,8,9,10,10a,11-hexahydro-6H-azepino
(4k): Isolated yield = 52%; yellow solid; m.p. 140.8-141.6 ℃ ; 1H NMR
(CDCl3, 600 MHz): δ = 0.98 (t, J = 7.2 Hz, 3 H), 1.74-1.78 (m, 2 H), 1.97-
2.03 (m, 1 H), 2.28-2.33 (m, 1 H), 2.48-2.51 (m, 1 H), 2.63-2.67 (m, 1 H),
3.98-4.02 (m, 2 H), 4.34 (t, J = 4.2 Hz, 1 H), 7.21-7.26 (m, 2 H), 7.32-7.34
trans-Methyl
10a-(4-chlorophenyl)-6,11-dioxo-7,8,9,10,10a,11-
hexahydro-6H-azepino[1,2-a] indole-10-carboxylate (4q): Isolated
yield = 70%; yellow solid; m.p. 185.6-186.4 ℃ ; 1H NMR (CDCl3, 600
MHz): δ = 1.75-1.78 (m, 2 H), 1.93-1.98 (m, 1 H), 2.24-2.29 (m, 1 H),
(m, 1 H), 7.37-7.39 (m, 2 H), 7.49 (d, J = 7.8 Hz, 1 H), 7.79 (d, J = 7.8 Hz, 2.44-2.47 (dd, J1 = 14.4 Hz, J2 = 3.0 Hz, 1 H), 2.62-2.66 (m, 1 H), 3.51 (s,
1 H), 9.14 (s, 1 H); 13C NMR (CDCl3, 150 MHz): δ = 12.8, 19.9, 25.4, 38.4, 3 H), 4.27 (t, J = 3.6 Hz, 1 H), 7.21-7.26 (m, 3 H), 7.34 (d, J = 8.4 Hz, 2
48.2, 60.8, 74.2, 115.2 (d, J = 4.2 Hz), 120.6 (d, J = 3.4 Hz), 124.2, 124.3
(d, J = 164.4 Hz), 127.9, 129.0, 133.3, 135.3 (d, J = 31.5 Hz), 152.3,
169.5, 172.9, 195.1; HRMS (ESI) calcd for C23H21F3NO4 [M+H]+
432.1423, found 432.1428.
H), 7.69-7.73 (m, 2 H), 8.80 (d, J = 8.4 Hz, 1 H); 13C NMR (CDCl3, 150
MHz): δ = 20.0, 25.4, 38.5, 47.8, 51.5, 73.2, 117.8, 121.4, 123.8, 124.0,
129.0, 132.6, 133.9, 136.2, 152.6, 169.8, 172.4, 195.4; HRMS (ESI)
calcd for C21H19ClNO4 [M+H]+ 384.1003, found 384.1009.
trans-Ethyl
6,11-dioxo-10a-(p-tolyl)-7,8,9,10,10a,11-hexahydro-6H-
trans-Ethyl
10a-(3-fluorophenyl)-6,11-dioxo-7,8,9,10,10a,11-
azepino[1,2-a]indole-10- carboxylate (4l): Isolated yield = 69%; yellow
solid; m.p. 123.4-124.8 ℃; 1H NMR (CDCl3, 600 MHz): δ = 0.88 (t, J =
6.6 Hz, 3 H), 1.72-1.74 (m, 1 H), 1.77-1.84 (m, 1 H), 1.99-2.05 (m, 1 H),
2.30 (s, 3 H), 2.31-2.36 (m, 1 H), 2.43-2.46 (m, 1 H), 2.58-2.62 (m, 1 H),
3.91-3.97 (m, 2 H), 4.27 (t, J = 4.2 Hz, 1 H), 7.12-7.15 (m, 4 H), 7.21-7.23
(m, 1 H), 7.67-7.70 (m, 2 H), 8.79 (d, J = 8.4 Hz, 1 H); 13C NMR (CDCl3,
150 MHz): δ = 12.6, 20.0, 20.1, 25.4, 38.5, 47.6, 60.5, 73.5, 117.8, 121.9,
123.7, 123.8, 129.5, 131.0, 135.9, 137.6, 152.7, 169.5, 172.8, 195.8;
HRMS (ESI) calcd for C23H24NO4 [M+H]+ 378.1705, found 378.1709.
hexahydro-6H-azepino[1,2-a] indole-10-carboxylate (4r): Isolated
yield = 67%; yellow solid; m.p. 129.7-130.4 ℃ ; 1H NMR (CDCl3, 600
MHz): δ = 0.89 (t, J = 7.2 Hz, 3 H), 1.74-1.83 (m, 2 H), 1.95-2.01 (m, 1 H),
2.27-2.32 (m, 1 H), 2.47-2.49 (m, 1 H), 2.63-2.66 (m, 1 H), 3.92-3.98 (m,
2 H), 4.23 (t, J = 3.6 Hz, 1 H), 6.99-7.07 (m, 3 H), 7.24-7.26 (m, 1 H),
7.33-7.37 (m, 1 H), 7.69-7.73 (m, 2 H), 8.80 (d, J = 8.4 Hz, 1 H); 13C
NMR (CDCl3, 150 MHz): δ = 12.6, 19.9, 25.5, 38.5, 47.7, 60.7, 73.2,
114.6 (d, J = 21.3 Hz), 117.9, 121.5, 123.8, 123.9, 130.3, 136.2, 136.9 (d,
J = 6.9 Hz), 152.6, 160.2 (d, J = 352.6 Hz), 169.1, 172.4, 195.1; HRMS
(ESI) calcd for C22H21FNO4 [M+H]+ 382.1445, found 382.1450.
trans-Methyl 6,11-dioxo-10a-(p-tolyl)-7,8,9,10,10a,11-hexahydro-6H-
azepino[1,2-a]indole-10- carboxylate (4m): Isolated yield
=
72%;
trans-Ethyl
3-chloro-6,11-dioxo-10a-(p-tolyl)-7,8,9,10,10a,11-
yellow solid; m.p. 197.1-198.3 ℃; 1H NMR (CDCl3, 600 MHz): δ = 1.73-
hexahydro-6H-azepino[1,2-a] indole-10-carboxylate (4s): Isolated
yield = 62%; yellow solid; m.p. 209.2-210.7 ℃ ; 1H NMR (CDCl3, 600
1.79 (m, 2 H), 1.99-2.05 (m, 1 H), 2.30 (s, 3 H), 2.32-2.35 (m, 1 H), 2.42-
2.45 (dd, J1 = 13.8 Hz, J2 = 3.0 Hz, 1 H), 2.59-2.62 (m, 1 H), 3.50 (s, 3 H), MHz): δ = 0.97 (t, J = 7.2 Hz, 3 H), 1.72-1.76 (m, 2 H), 1.97-2.03 (m, 1 H),
4.31 (t, J = 3.6 Hz, 1 H), 7.09-7.20 (m, 4 H), 7.21-7.24 (m, 1 H), 7.68-7.71
(m, 2 H), 8.80 (d, J = 8.4 Hz, 1 H); 13C NMR (CDCl3, 150 MHz): δ = 20.1,
25.4, 38.5, 47.7, 51.4, 73.5, 117.7, 121.6, 123.7, 129.5, 130.8, 135.9,
137.6, 152.6, 170.1, 172.7, 195.9; HRMS (ESI) calcd for C22H22NO4
[M+H]+ 364.1549, found 364.1554.
2.29-2.33 (m, 4 H), 2.44-2.47 (m, 1 H), 2.59-2.63 (m, 1 H), 3.97-4.01 (m,
2 H), 4.26 (t, J = 3.6 Hz, 1 H), 7.08-7.17 (m, 4 H), 7.19-7.21 (dd, J1 = 7.8
Hz, J2 = 1.8 Hz, 1 H), 7.60 (d, J = 7.8 Hz, 1 H), 8.87 (d, J = 1.8 Hz, 1 H);
13C NMR (CDCl3, 150 MHz): δ = 12.8, 19.9, 20.1, 25.4, 38.3, 47.7, 60.6,
73.9, 118.2, 120.3, 124.4, 124.5, 139.6, 130.6, 137.8, 142.3, 152.9,
169.5, 172.8, 194.6; HRMS (ESI) calcd for C23H23ClNO4 [M+H]+ 412.1316,
found 412.1320.
trans-Ethyl
10a-(4-ethylphenyl)-6,11-dioxo-7,8,9,10,10a,11-
hexahydro-6H-azepino[1,2-a] indole-10-carboxylate (4n): Isolated
yield = 72%; yellow solid; m.p. 159.8-161.1 ℃ ; 1H NMR (CDCl3, 600
MHz): δ = 0.88 (t, J = 7.2 Hz, 3 H), 1.94 (t, J = 7.8 Hz, 3 H), 1.71-1.75 (m,
1 H), 1.77-1.84 (m, 1 H), 1.99-2.05 (m, 1 H), 2.32-2.36 (m, 1 H), 2.43-
2.46 (m, 1 H), 2.59-2.62 (m, 3 H), 3.90-3.99 (m, 2 H), 4.28 (t, J = 3.6 Hz,
1 H), 7.10-7.17 (m, 4 H), 7.20-7.23 (m, 1 H), 7.67-7.70 (m, 2 H), 8.80 (d,
J = 8.4 Hz, 1 H); 13C NMR (CDCl3, 150 MHz): δ = 12.6, 14.3, 20.0, 25.4,
27.4, 38.5, 47.6, 60.5, 73.5, 117.8, 121.9, 123.7, 123.8, 125.0, 128.3,
131.2, 135.9, 143.8, 152.7, 169.5, 172.8, 195.9; HRMS (ESI) calcd for
C24H26NO4 [M+H]+ 392.1862, found 392.1868.
trans-Ethyl
7,8,9,10,10a,11-hexahydro-6H-azepino
3-chloro-10a-(4-chlorophenyl)-6,11-dioxo-
[1,2-a]indole-10-carboxylate
(4t): Isolated yield = 45%; yellow solid; m.p. 183.8-185.0 ℃ ; 1H NMR
(CDCl3, 600 MHz): δ = 0.98 (t, J = 7.2 Hz, 3 H), 1.74-1.78 (m, 2 H), 1.90-
1.96 (m, 1 H), 2.23-2.28 (m, 1 H), 2.45-2.48 (m, 1 H), 2.62-2.66 (m, 1 H),
3.97-4.01 (m, 2 H), 4.23 (t, J = 3.6 Hz, 1 H), 7.19-7.23 (m, 3 H), 7.35 (d, J
= 8.4 Hz, 2 H), 7.61 (d, J = 7.8 Hz, 1 H), 8.86 (d, J = 1.8 Hz, 1 H); 13C
NMR (CDCl3, 150 MHz): δ = 12.8, 19.9, 25.4, 38.3, 47.8, 60.8, 73.7,
118.2, 120.0, 124.5, 124.6, 129.1, 132.3, 134.0, 142.7, 152.9, 169.2,
172.5, 194.1; HRMS (ESI) calcd for C22H20Cl2NO4 [M+H]+ 432.0769,
found 432.0774.
trans-Ethyl
10a-(4-methoxyphenyl)-6,11-dioxo-7,8,9,10,10a,11-
hexahydro-6H-azepino[1,2-a] indole-10-carboxylate (4o): Isolated
yield = 77%; yellow solid; m.p. 143.3-144.6 ℃ ; 1H NMR (CDCl3, 600
trans-Ethyl
6,11-dioxo-10a-(thiophen-2-yl)-7,8,9,10,10a,11-
MHz): δ = 0.88 (t, J = 7.2 Hz, 3 H), 1.71-1.83 (m, 2 H), 1.98-2.04 (m, 1 H), hexahydro-6H-azepino[1,2-a] indole-10-carboxylate (4u): Isolated
2.32-2.37 (m, 1 H), 2.43-2.46 (m, 1 H), 2.59-2.62 (m, 1 H), 3.76 (s, 3 H),
3.91-3.97 (m, 2 H), 4.24 (t, J = 3.6 Hz, 1 H), 6.87 (d, J = 8.4 Hz, 2 H),
7.10-7.17 (m, 2 H), 7.21-7.24 (m, 1 H), 7.68-7.70 (m, 2 H), 8.79 (d, J =
yield = 66%; brown solid; m.p. 143.7-144.9 ℃ ; 1H NMR (CDCl3, 600
MHz): δ = 0.89 (t, J = 6.6 Hz, 3 H), 1.74-1.78 (m, 2 H), 1.99-2.05 (m, 1 H),
2.42-2.50 (m, 2 H), 2.64-2.68 (m, 1 H), 3.90-3.99 (m, 2 H), 4.18 (t, J = 3.6
8.4 Hz, 1 H); 13C NMR (CDCl3, 150 MHz): δ = 12.6, 20.0, 25.3, 38.4, 47.5, Hz, 1 H), 6.98-6.99 (dd, J1 = 4.8 Hz, J2 = 0.6 Hz, 1 H), 7.08-7.09 (m, 1 H),
54.5, 60.5, 73.1, 114.2, 117.8, 121.8, 123.7, 125.6, 126.3, 135.9, 152.6,
158.8, 169.5, 172.8, 195.9; HRMS (ESI) calcd for C23H24NO5 [M+H]+
394.1654, found 394.1659.
7.22-7.24 (m, 1 H), 7.35-7.36 (m, 1 H), 7.67-7.72 (m, 2 H), 8.76 (d, J =
8.4 Hz, 1 H); 13C NMR (CDCl3, 150 MHz): δ = 12.6, 19.9, 26.0, 38.6, 48.3,
60.6, 72.3, 117.9, 121.5, 121.7, 123.8, 124.4, 127.1, 135.7, 135.9, 152.4,
169.2, 172.6, 195.0; HRMS (ESI) calcd for C20H20NO4 S [M+H]+ 370.1113,
found 370.1117.
trans-Ethyl
10a-(4-chlorophenyl)-6,11-dioxo-7,8,9,10,10a,11-
hexahydro-6H-azepino[1,2-a] indole-10-carboxylate (4p): Isolated
yield = 65%; yellow solid; m.p. 75.2-76.7 ℃; 1H NMR (CDCl3, 600 MHz):
δ = 0.89 (t, J = 7.2 Hz, 3 H), 1.73-1.84 (m, 2 H), 1.91-1.97 (m, 1 H), 2.25-
2.30 (m, 1 H), 2.45-2.48 (m, 1 H), 2.62-2.65 (m, 1 H), 3.92-3.98 (m, 2 H),
4.24 (t, J = 3.6 Hz, 1 H), 7.21-7.26 (m, 3 H), 7.33 (d, J = 7.8 Hz, 2 H),
trans-Ethyl
10a-cyclopropyl-6,11-dioxo-7,8,9,10,10a,11-hexahydro-
6H-azepino[1,2-a]indole- 10-carboxylate (4v): Isolated yield = 55%;
brown solid; m.p. 139.5-141.2 ℃; 1H NMR (CDCl3, 600 MHz): δ = 0.24-
0.28 (m, 1 H), 0.50-0.65 (m, 3 H), 0.88 (t, J = 6.6 Hz, 3 H), 1.51-1.55 (m,
5
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10.1002/ejoc.202000243
European Journal of Organic Chemistry
FULL PAPER
1 H), 1.69-1.76 (m, 1 H), 1.91-1.94 (m, 1 H), 2.31-2.37 (m, 1 H), 2.51-
2.54 (m, 1 H), 2.87-2.90 (m, 1 H), 2.95-3.00 (m, 1 H), 3.60 (t, J = 4.2 Hz,
1 H), 3.88-3.92 (m, 2 H), 7.18-7.20 (m, 1 H), 7.61-7.63 (m, 1 H), 7.70 (d,
J = 7.2 Hz, 1 H), 8.63 (d, J = 8.4 Hz, 1 H); 13C NMR (CDCl3, 150 MHz): δ
= 0.7, 3.7, 13.4, 14.5, 20.9, 26.3, 40.1, 50.1, 61.1, 69.8, 119.2, 123.1,
124.1, 124.2, 136.5, 153.6, 170.5, 172.5, 198.0; HRMS (ESI) calcd for
C19H22NO4 [M+H]+ 328.1549, found 328.1555.
[1]
For selected recent examples, see: a) A. J. Kochanowska-Karamyan, M.
T. Hamann, Chem. Rev. 2010, 110, 4489-4497; b) Y. Yang, Y. Bai, S.
Sun, M. Dai, Org. Lett. 2014, 16, 6216-6219; c) K. Higuchi, S. Suzuki, R.
Ueda, N. Oshima, E. Kobayashi, M. Tayu, T. Kawasaki, Org. Lett. 2015,
17, 154-157; d) R. O. Torres-Ochoa, T. Buyck, Q. Wang, J. Zhu, Angew.
Chem. Int. Ed. 2018, 57, 5679-5683; e) Y. Liu, H. Wang, Chem.
Commun. 2019, 55, 3544-3547; f) G. Li, C. Piemontesi, Q. Wang, J.
Zhu, Angew. Chem. Int. Ed. 2019, 58, 2870-2874.
[2]
For first isolation and characterization of isatisine A, see: J. Liu, Z.
Jiang, R. Wang, Y. Zheng, J. Chen, X. Zhang, Y. Ma, Org. Lett. 2007, 9,
4127-4129; For recent total syntheses of isatisine A, see: a) A.
Karadeolian, M. A. Kerr, Angew. Chem., Int. Ed. 2010, 49, 1133-1135;
b) P. Patel, C. V. Ramana, J. Org. Chem. 2012, 77, 10509-10515; c) J.
Lee, J. S. Panek, J. Org. Chem. 2015, 80, 2959-2971; d) M. Xiao, W.
Wu, L. Wei, X. Jin, X. Yao, Z. Xie, Tetrahedron 2015, 71, 3705-3714.
G. Cheng, D. Li, B. Hou, X. Li, L. Liu, Y. Chen, P. Lunga, A. Khan, Y.
Liu, Z. Zuo, X. Luo, J. Nat. Prod. 2016, 79, 2158-2166.
trans-Ethyl
10a-butyl-6,11-dioxo-7,8,9,10,10a,11-hexahydro-6H-
azepino[1,2-a]indole-10- carboxylate (4w): Isolated yield = 45%; red
solid; m.p. 177.2-178.4 ℃; 1H NMR (CDCl3, 600 MHz): δ = 0.77 (t, J =
7.2 Hz, 3 H), 0.83 (t, J = 7.2 Hz, 3 H), 0.86-0.89 (m, 1 H), 0.96-1.01 (m, 1
H), 1.17-1.25 (m, 4 H), 1.79-1.93 (m, 3 H), 2.14-2.20 (m, 1 H), 2.31-2.37
(m, 1 H), 2.42-2.46 (m, 1 H), 2.80-2.82 (m, 2 H), 3.42 (t, J = 3.6 Hz, 1 H),
3.83-3.87 (m, 2 H), 7.21-7.23 (m, 1 H), 7.63-7.66 (m, 1H), 7.76 (d, J = 7.8
Hz, 1 H), 8.66 (d, J = 8.4 Hz, 1 H); 13C NMR (CDCl3, 150 MHz): δ = 12.6,
12.8, 20.0, 21.9, 23.2, 24.8, 34.7, 38.4, 48.4, 60.3, 70.4, 118.1, 122.1,
123.3, 124.3, 135.9, 153.0, 169.5, 171.7, 200.2; HRMS (ESI) calcd for
C20H26NO4 [M+H]+ 344.1862, found 344.1866.
[3]
[4]
a) A. Rahman; M. Bashir, Planta Med. 1983, 49, 124; b) A. Rahman, A.
Pervin, A. Muzaffar, K. T. D. De Silva, W. S. J. Silva. Phytochemistry
1989, 28, 3221-3225;
[5]
For selected recent examples, see: For selected recent examples, see:
a) Y. Zhao, Y. Wang, J. Cao, Y. Liang, P. Xu, Org. Lett. 2014, 16, 2438-
2441; b) D. A. Petrone, A. Yen, N. Zeidan, M. Lautens, Org. Lett. 2015,
17, 4838-4841; c) B. Prasad, R. Adepu, A. K. Sharma, M. Pal, Chem.
Commun. 2015, 51, 1259-1262; d) K. Higuchi, S. Suzuki, R. Ueda, N.
Oshima, E. Kobayashi, M. Tayu, Tomomi Kawasaki, Org. Lett. 2015, 17,
154-157; e) A. V. Varlamov, N. I. Guranova, R. A. Novikov, V. V.
Ilyushenkova, V. N. Khrustalev, N. S. Baleeva, T. N. Borisova, L. G.
Voskressensky, RSC Adv. 2016, 6, 12642-12646; f) R. Liang, K. Wang,
L. Song, W. Sheng. Y. Jia, RSC Adv. 2019, 9, 13959-13967; g) R. Kim,
A. J. Ferreira, C. M. Beaudry, Angew. Chem., Int. Ed. 2019, 58, 12595-
12598; h) A. D. Marchese, F. Lind, A. E. Mahon, H. Yoon, M. Lautens,
Angew. Chem., Int. Ed. 2019, 58, 5095-5099.
2-(3-Oxo-2-phenylindolin-2-yl)-1H-indene-1,3(2H)-dione (5a): Isolated
yield = 44%; brown solid; m.p. 157.2-158.6 ℃; 1H NMR (DMSO-d6, 600
MHz): δ = 4.81 (s, 1 H), 6.78-6.81 (m, 1 H), 6.86 (d, J = 7.8 Hz, 1 H),
7.32-7.34 (m, 1 H), 7.37-7.39 (m, 2 H), 7.44-7.48 (m, 2 H), 7.52-7.54 (m,
2 H), 7.90-7.92 (m, 1 H), 7.94-7.95 (m, 1 H), 7.98-8.02 (m, 3 H); 13C NMR
(DMSO-d6, 150 MHz): δ = 59.1, 71.3, 112.2, 118.8, 119.0, 123.2, 123.3,
125.0, 126.5, 127.8, 128.6, 136.5, 136.5, 137.1, 137.4, 142.1, 143.4,
161.6, 196.8, 197.6, 198.9; HRMS (ESI) calcd for C23H16NO3 [M+H]+
354.1130, found 354.1134.
2-(2-Butyl-3-oxoindolin-2-yl)-1H-indene-1,3(2H)-dione (5b): Isolated
yield = 40%; red solid; m.p. 163.7-165.1 ℃; 1H NMR (CDCl3, 600 MHz):
δ = 0.84 (t, J = 6.6 Hz, 3 H), 1.09-1.17 (m, 1 H), 1.23-1.31 (m, 3 H), 2.15-
2.28 (m, 2 H), 3.59 (s, 1 H), 4.42 (s, 1 H), 6.73 (d, J = 7.8 Hz, 1 H), 6.87-
6.89 (m, 1 H), 7.38-7.40 (m, 1 H), 7.70 (d, J = 7.8 Hz, 1 H), 7.78-7.82 (m,
2 H), 7.84-7.85 (m, 1 H), 7.94-7.95 (m, 1H); 13C NMR (CDCl3, 150 MHz):
δ = 13.0, 21.9, 23.8, 34.0, 57.1, 68.9, 111.8, 119.2, 121.7, 122.2, 122.5,
123.7, 134.7, 135.0, 136.0, 141.6, 142.2, 159.5, 195.3, 198.1, 200.8;
HRMS (ESI) calcd for C21H20NO3 [M+H]+ 334.1443, found 334.1448.
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Supporting Information
General information, and NMR are presented in the Supporting
Information.
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Acknowledgements
This work was supported by National Natural Science
Foundation of China Grants (21302096), Natural Science
Foundation of Jiangsu Province-Grants (BK20171449), Qing
Lan Project, the National First-class Disciplines (PNFD), China,
and the Priority Academic Program Development of Jiangsu
Higher Education Insitutions (PAPD), China.
Keywords: indolin-3-ones • insertion reaction • N-fused seven-
membered • one-pot • Palladium-catalyzed
6
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Entry for the Table of Contents
Heterocycles Synthesis:
A novel insertion reaction of cyclic C-acylimines into cyclic β-diketones to construct N-fused seven-membered multifunctional
polycyclic indoline-3-one derivatives has been described, which has shown good tolerance of various functional groups. The
corresponding products were obtained in moderate to good yields under mild reaction conditions.
8
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