New formal (3+3) cycloaddition of enaminones for forming tetracyclic indolo[2,3-b]quinolines under microwave irradiation

Article abstract of DOI:10.1016/j.tet.2013.11.022

Concise and efficient base-promoted domino formal (3+3) cycloaddition has been established for the formation of tetracyclic indolo[2,3-b]quinoline derivatives under microwave heating. The present methodology shows attractive properties, such as the maximum efficiency of a process, short reaction periods, and operational simplicity, and it can avoid time-consuming and costly syntheses, tedious work-up and isolation of intermediate. This chemistry provides a facile and promising synthetic strategy to construction of tetracyclic indolo[2,3-b]quinoline skeleton.

Full text of DOI:10.1016/j.tet.2013.11.022

Tetrahedron 70 (2014) 1004e1010
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
New formal (3þ3) cycloaddition of enaminones for forming
tetracyclic indolo[2,3-b]quinolines under microwave irradiation
*
Meng-Yuan Li, Hai-Wei Xu, Wei Fan, Qin Ye, Xue Wang, Bo Jiang , Shu-Liang Wang,
*
Shu-Jiang Tu
School of Chemistry and Chemical Engineering, and Jiangsu Key Laboratory of Green Synthetic Chemistry for Functional Materials,
Jiangsu Normal University, Xuzhou 221116, Jiangsu, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
Concise and efficient base-promoted domino formal (3þ3) cycloaddition has been established for the
formation of tetracyclic indolo[2,3-b]quinoline derivatives under microwave heating. The present
methodology shows attractive properties, such as the maximum efficiency of a process, short reaction
periods, and operational simplicity, and it can avoid time-consuming and costly syntheses, tedious work-
up and isolation of intermediate. This chemistry provides a facile and promising synthetic strategy to
construction of tetracyclic indolo[2,3-b]quinoline skeleton.
Received 7 September 2013
Received in revised form 30 October 2013
Accepted 7 November 2013
Available online 15 November 2013
Keywords:
Ó 2013 Elsevier Ltd. All rights reserved.
Formal (3þ3) cycloaddition
Indolo[2,3-b]quinoline
Microwave heating
Enaminones
1. Introduction
The efficient construction of multicyclic skeletons with chemical
and biomedical importance is an active theme in organic synthesis.
Among these skeletons, the structurally diverse pyrido[2,3-b]in-
dole (a
-carboline I, Fig. 1) commonly exist in nature,1e3 represented
by grossularine-1 (II), grossularine-2 (III), mescengricin (IV), which
exhibit a broad range of biological activities.4 Furthermore, indolo
[2,3-b]quinoline unit is the precursor to cryptotakieine (V) (also
known as neocryptolepine) alkaloid,5 one of the major metabolites
out of the thirteen characterized alkaloids from Cryptolepis san-
guinolenta,6 which exhibited antitumor activity and DNA binding
properties.7 Because of their unique chemical and biological char-
acteristics, many methodologies for the synthesis of indolo[2,3-b]
quinolines have been developed. Most of them involved reduction
cyclization of o,o0-dinitro- -cyanodibenzyl,8 thermal de-
a
composition of adequate triazole,9 annelation of indoles10 and
other methods.11 Despite these limited indolo[2,3-b]quinoline
syntheses, an exploration of a facile protocol for the direct forma-
tion of the indolo[2,3-b]quinoline skeleton and its multi-
functionalizations would be highly favorable.
Modern organic synthesis has benefited from the development
of high-efficient synthetic strategy for the selective construction of
potentially useful target compounds. Domino reactions, being one
Fig. 1. Natural products with indole subunits.
of the most effective methods to improve chemical efficiency, can
implement reaction cascades and generate the structural diversity
of biologically important molecules by simultaneous combination
of multiple transformations in a single pot.12 Often mild and envi-
ronmentally friendly, domino reactions also provide a shortened
and atom-economical synthesis, thereby minimizing the genera-
tion of waste and rendering the transformations green.13 In recent
years, various domino reactions toward the formation of polycyclic
fused azaheterocycles have been extensively studied.14 In the past
* Corresponding authors. E-mail address: laotu@jsnu.edu.cn (S.-J. Tu).
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.11.022

M.-Y. Li et al. / Tetrahedron 70 (2014) 1004e1010
1005
Table 1
several years, we have developed a series of domino reactions for
Optimization of the catalysts for compound 3a
the construction of multiple functional ring structures of chemical
and pharmaceutical importance.15,16 As a continue of our works on
this project, we now developed domino [3þ3] heterocyclization of
3-aroylidene-2-oxindoles 1 with enaminones 2 leading to the for-
mation of polyfunctionalized indolo[2,3-b]quinoline derivatives 3
in good yields (Scheme 1). The present work represents the special
example for selective construction of these types of tetracyclic
indolo[2,3-b]quinolines through decarbonylation of lactams.
Entry
Base/equiv
T/ꢀC
Time/min
Yield/%
1
2
3
4
5
6
7
8
K2CO3 (1.0)
NaOH (1.0)
t-BuOK (1.0)
EtONa (1.0)
EtONa (1.0)
EtONa (1.0)
EtONa (1.0)
EtONa (1.0)
80
80
80
12
12
12
12
12
12
12
2 ha
43
52
32
68
75
85
83
72
80
100
110
120
110
a
Conventional heating.
7). Subsequently, the same reaction was investigated under classi-
cal heating (CH) conditions at 110 ꢀC for 120 min, providing the
product 3a in 72% yield (Table 1, entry 8).
With this result in hand, a library of new multi-functionalized
indolo[2,3-b]quinoline derivatives 3 was synthesized in order to
evaluate the scope of the protocol (Table 2). The effect of different
groups bound to enaminones was evaluated at first, reacting 1a
with structurally diverse enaminones. The electronic characteris-
tics of the substituent attached to the para position of the aromatic
ring (electron-donating or electron-withdrawing) did not affect
performance of the transformation, and the corresponding indolo
[2,3-b]quinolines were obtained in very high yield. Notably, when
N-aryl enaminones with two MeO groups at the 3,4-positions was
employed, the respective product was obtained in 73% yield. Fur-
thermore, steric effects did not significantly affect the reaction.
Using ortho-bromo- and ortho-iodophenyl enaminones, the corre-
sponding products 3h and 3j were delivered in good yield,
Scheme 1. Domino synthesis of indolo[2,3-b]quinoline derivatives.
2. Results and discussion
3-Aroylidene-2-oxindoles are versatile and readily obtainable
reagents, and their chemistry has received considerable attention
in recent years.17 It has been reported that when a mixture of 3-
aroylidene-2-oxindoles and in situ generated
was refluxed in HOAc, pentasubstituted pyrroles were produced
(Scheme 2).18 During this project, we found that when
-enamino
b-enamino ester
b
ester employed in the above literature were replaced by enami-
nones 2 at 110 ꢀC used HOAc as a promoter under microwave ir-
radiation, the reaction did not proceed. When the reaction
condition was changed to basic condition, the reaction occurred in
another direction to form multifunctionalized indolo[2,3-b]quino-
lines that are important scaffolds for organic synthesis and drug
design in pharmaceutical sciences (Scheme 2).19 Encouraged by this
initial result, we then made many efforts on optimizing reaction
conditions.
Table 2
Domino synthesis of indolo[2,3-b]quinoline 3 under MWa
Entry
3
Ar1
R
Ar2
R1 Time/ Yield/%b
min
1
2
3
4
5
6
7
8
3a 4-MeOC6H4 (1a)
3b 4-MeOC6H4 (1a)
3c 4-MeOC6H4 (1a)
3d 4-MeOC6H4 (1a)
3e 4-MeOC6H4 (1a)
3f 4-MeOC6H4 (1a)
3g 4-MeOC6H4 (1a)
3h 4-MeOC6H4 (1a)
3i 4-MeOC6H4 (1a)
3j 4-MeC6H4 (1b)
3k 4-MeC6H4 (1b)
3l 4-MeC6H4 (1b)
H
H
H
H
H
H
H
H
H
H
H
H
4-MeC6H4 (2a)
4-MeOC6H4 (2b)
3,4-(MeO)2C6H3 (2c) Me 16
C6H5 (2d)
4-FC6H4 (2e)
4-ClC6H4 (2f)
4-BrC6H4 (2g)
2-BrC6H4 (2h)
2-IC6H4 (2i)
4-BrC6H4 (2g)
2-BrC6H4 (2h)
2-IC6H4 (2i)
Me 12
Me
85
83
73
75
80
81
86
83
81
85
78
76
80
84
82
86
81
83
84
76
78
73
83
78
80
79
8
Me 15
Me
Me
Me
9
8
8
Me 10
Me 12
Me 12
Me 10
Me 15
Me 10
9
Scheme 2. The reaction of 3-aroylidene-2-oxindoles.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
3m 4-MeC6H4 (1c) 5-Me 4-MeC6H4 (2a)
3n 4-MeC6H4 (1c) 5-Me 4-BrC6H4 (2g)
We started this study by subjecting a preformed 3-p-methox-
yphenacylideneoxindole 1a and 5,5-dimethyl-3-(4-methylpheny
lamino)cyclohex-2-enone 2a in ethanol at 80 ꢀC under micro-
wave irradiation, using different bases (1.0 equiv). The incomplete
reaction was observed using various bases, such as K2CO3, NaOH, t-
BuOK, and EtONa as a base catalyst. Sodium ethylate (EtONa) was
proven to be the best base (Table 1, entry 4). Subsequently, the
reaction catalyzed by NaOEt was performed and repeated many
times in different temperatures in a sealed vessel under microwave
irradiation for 12 min. The best yield of product 3a (85%) was ob-
tained in ethanol as the reaction temperature was increased to
110 ꢀC (Table 1, entry 6). A further increase in reaction temperature
failed to improve the yield of the desired product 3a (Table 1, entry
Me
9
3o 4-FC6H4 (1d)
3p 4-FC6H4 (1d)
3q 4-FC6H4 (1d)
3r 4-ClC6H4 (1e)
3s 4-ClC6H4 (1e)
3t 4-MeC6H4 (1b)
3u 4-MeC6H4 (1b)
H
H
H
H
H
H
H
4-ClC6H4 (2f)
4-BrC6H4(2g)
2-IC6H4 (2i)
4-MeC6H4 (2a)
4-BrC6H4 (2g)
4-ClC6H4 (2j)
4-BrC6H4 (2k)
Me 11
Me 10
Me 10
Me 13
Me 11
H
H
H
H
H
H
H
14
14
16
11
13
12
14
3v 4-MeC6H4 (1c) 5-Me 4-BrC6H4 (2k)
3w 4-MeOC6H4 (1a)
3x 4-MeOC6H4 (1a)
3y 4-MeOC6H4 (1a)
3z 4-MeOC6H4 (1a)
H
H
H
H
4-FC6H4 (2l)
4-ClC6H4 (2j)
4-BrC6H4 (2k)
2-IC6H4 (2m)
a
Reagents and conditions: 110 ꢀC, EtOH (1.5 mL) microwave heating.
Isolated yield.
b

1006
M.-Y. Li et al. / Tetrahedron 70 (2014) 1004e1010
respectively. Next, the influence of the 3-aroylidene-2-oxindoles
was evaluated, employing 2 with different functionalities at-
tached at the para position of the phenyl ring, including methyl,
fluoro, and chloro groups. The results indicated that both electron-
withdrawing and electron-donating groups are suitable substrates,
affording the corresponding products 3jes in 76e86% yield. As an
extension of the above study, 5,5-unsubstituted enaminones was
subjected with diverse 3-aroylidene-2-oxindoles to investigate the
possibility of this transformation. Substituents on the phenyl ring of
1 and 2 were all successfully engaged in this reaction, leading to the
final products with good yields (3tez). Furthermore, groups like
bromide and chloride were well tolerated. These functional groups
provide ample opportunity for further functional group manipu-
lations, for example, such as modern cross-coupling reactions. It
can be noted that the results exhibit the scope and generality of the
domino reaction with respect to a range of enaminone and 3-
aroylidene-2-oxindole substrates.
initial Michael addition (1 to A), tautomerism (A to B), intra-
molecular cyclization (C to D), and subsequent dehydration and
aromatization (D to 3). This type of hydrogen loss is well
precedented.21
3. Conclusion
In summary, an operationally simple and highly efficient base-
promoted formal (3þ3) cycloaddition strategy for the formation
of tetracyclic indolo[2,3-b]quinoline derivatives has been de-
veloped in this work. The mild conditions, the maximum efficiency
of a process and short reaction periods as well as operational
simplicity are clearly represented in this one-pot transformation
that provides an elegant methodology for the synthesis of highly
functionalized indolo[2,3-b]quinolines. Further investigations to
evaluate the applicability of this process to a broad range of sub-
strates, synthesizing more complex products and testing their bi-
ological activity is an ongoing goal of research in our laboratory.
The structures of the indolo[2,3-b]quinolin were fully charac-
terized by 1H and 13C NMR, HRMS, IR spectra, and the structure of
compound 3w was further confirmed by single crystal X-ray dif-
fraction (Fig. 2).
4. Experimental section
4.1. General
Microwave irradiation was carried out with Initiator from
Biotage Company, Sweden. Melting points were determined in
open capillaries and were uncorrected. IR spectra were taken on
a FT-IR-Tensor 27 spectrometer in KBr pellets and reported in cmꢁ1
.
1H NMR spectra were measured on a Bruker DPX 400 MHz spec-
trometer in DMSO-d6 with chemical shift ( ) given in parts per
d
million relative to TMS as internal standard. HRMS (ESI) was de-
termined by using microTOF-Q II HRMS/MS instrument (Bruker). X-
ray crystallographic analysis was performed with a Siemens SMART
CCD and a Siemens P4 diffractometer.
4.2. Typical procedure for the preparation of 11-(4-methoxy
benzoyl)-3,3-dimethyl-5-(p-tolyl)-2,3,4,5-tetrahydro-1H-in-
dolo[2,3-b]quinolin-1-one (3a)
Fig. 2. ORTEP drawing of 3w.20
Typically,
5,5-dimethyl-3-(4-methylphenylamino)cyclohex-2-
enone (2a, 1.1 mmol, 1.1 equiv) was introduced in a 10-mL InitiatorÔ
reaction vial, 3-p-methoxyphenacylideneoxindole (1a, 1.0 mmol,
1.0 equiv), EtONa (1.0 mmol, 1.0 equiv), and EtOH (1.5 mL) were suc-
cessively added. Subsequently, the reaction vial was capped and then
pre-stirred for 20 s. The mixture was irradiated (Time: 12 min, Tem-
perature: 110 ꢀC; Absorption Level: High; Fixed Hold Time) until TLC
(petroleum ether: acetic ether 3:1) revealed that conversion of the
starting material 1awas complete. The reaction mixturewas cooled to
room temperature. Next, the system was diluted with cold water
(20 mL) and neutralized by diluted acidic solution. The resulting
precipitate was collected by filtration and was purified by flash col-
umn chromatography to afford the desired pure product 3a.
Yellow solid; mp: >300 ꢀC.
On the basis of literature reports18 and observations of the above
results, a possible mechanism has been proposed for the formation
of indolo[2,3-b]quinoline derivatives as shown in Scheme 3. The
reaction involves the ring closure cascade reactions that consist of
IR (KBr, v, cmꢁ1): 2957, 1671, 1668, 1600, 1510, 1415, 1304, 1261,
1246, 1166, 1075, 1020, 856, 793, 622 cmꢁ1
;
1H NMR (400 MHz, CDCl3) (
d
ppm): 7.94 (d, J¼7.2 Hz, 1H, ArH),
7.78e7.62 (m, 1H, ArH), 7.50 (d, J¼8.0 Hz, 1H, ArH), 7.39 (s, 1H, ArH),
7.23 (s,1H, ArH), 7.03 (s,1H, ArH), 6.95 (d, J¼7.4 Hz,1H, ArH), 3.85 (s,
3H, OCH3), 2.74 (s, 2H, CH2), 2.53 (s, 3H, CH3), 2.49 (s, 2H, CH2), 1.10
(s, 6H, CH3).
13CNMR(100MHz, CDCl3)(
dppm)194.0,193.9,163.8,160.5,155.8,
154.4, 151.2, 140.5, 135.2, 131.4, 131.2, 130.9, 129.4, 128.7, 127.1, 126.9,
122.8, 121.2, 119.2, 114.3, 113.4, 55.5, 50.5, 42.5, 33.1, 28.4, 27.9, 21.5.
HRMS (ESI) m/z: calcd for C32H29N2O3: 489.2178 [MþH]þ;
found: 489.2173.
Scheme 3. The reasonable mechanism for the formation of 3.

M.-Y. Li et al. / Tetrahedron 70 (2014) 1004e1010
1007
4.3. 11-(4-Methoxybenzoyl)-5-(4-methoxyphenyl)-3,3-dime
(s, 2H, 2H, CH2), 2.61e2.33 (m, 2H, CH2), 1.11 (s, 3H, CH3), 1.09 (s, 3H,
thyl-2,3,4,5-tetrahydro-1H-indolo[2,3-b]quinolin-1-one (3b)
CH3).
13C NMR (100 MHz, CDCl3) (
d ppm): 193.8, 193.7, 163.9,
Yellow solid; mp: >300 ꢀC.
163.2(1JCF¼249.5 Hz), 155.8, 154.4, 150.8, 140.9, 130.9,
129.5(3JCF¼8.8 Hz), 129.4, 129.2, 129.0, 123.1, 122.9 (4JCF¼2.1 Hz),
121.5, 119.2, 118.0 (2JCF¼22.9 Hz), 117.9, 117.7, 114.3, 113.5, 55.5, 50.4,
42.6, 33.1, 28.5, 27.9.
IR (KBr, v, cmꢁ1): 3415, 2956, 1673, 1656, 1599, 1511, 1412, 1304,
1264, 1231, 1144, 1022, 857, 826, 741 cmꢁ1
;
1H NMR (400 MHz, CDCl3) (
d
ppm): 7.94 (d, J¼8.4 Hz, 2H, ArH),
7.69 (d, J¼8.0 Hz,1H, ArH), 7.49 (d, J¼7.6 Hz, 1H, ArH), 7.45e7.34 (m,
2H, ArH), 7.28 (s, 1H, ArH), 7.18 (t, J¼8.0 Hz, 2H, ArH), 7.02 (t,
J¼6.4 Hz, 1H, ArH), 6.94 (d, J¼8.4 Hz, 2H, ArH), 3.94 (s, 3H, OCH3),
3.85 (s, 3H, OCH3), 2.74 (s, 2H, CH2), 2.48 (d, J¼7.2 Hz, 2H, CH2), 1.10
(s, 3H, CH3), 1.08 (s, 3H, CH3).
HRMS (ESI) m/z: calcd for C31H26FN2O3: 493.1927 [MþH]þ;
found: 493.1954.
4.7. 5-(4-Fluorophenyl)-11-(4-methoxybenzoyl)-3,3-
dimethyl-2,3,4,5-tetrahydro-1H-indolo[2,3-b]quinolin-1-one
(3f)
13C NMR (100 MHz, CDCl3) (
d ppm): 194.0, 193.9, 163.9, 160.6,
151.5, 130.9, 130.3, 130.2, 129.4, 128.8, 128.5, 128.3, 125.5, 125.1,
122.8, 121.4, 119.1, 115.9, 114.3, 55.7, 55.5, 50.5, 42.6, 33.1, 28.5, 27.9.
HRMS (ESI) m/z: calcd for C32H29N2O4: 505.2127 [MþH]þ;
found: 505.2126.
Yellow solid, mp: >300 ꢀC.
IR (KBr, v, cmꢁ1): 2957, 2871, 1672, 1624, 1602, 1520, 1510, 1432,
1305, 1245, 1109, 1016, 855, 821, 770 cmꢁ1
.
1H NMR (400 MHz, CDCl3) (
d
ppm): 7.92 (d, J¼8.4 Hz, 2H, ArH),
7.67 (t, J¼8.0 Hz, 3H, ArH), 7.48 (d, J¼7.6 Hz, 1H, ArH), 7.44 (d,
J¼8.4 Hz, 1H, ArH), 7.39 (t, J¼7.6 Hz, 1H, ArH), 7.32 (d, J¼8.4 Hz, 1H,
ArH), 7.03 (t, J¼7.6 Hz, 1H, ArH), 6.92 (d, J¼8.4 Hz, 2H, ArH), 3.83 (s,
3H, OCH3), 2.70 (s, 2H, CH2), 2.44 (d, J¼7.2 Hz, 2H, CH2), 1.08 (s, 3H,
CH3), 1.06 (s, 3H, CH3).
4.4. 5-(3,4-Dimethoxyphenyl)-11-(4-methoxybenzoyl)-3,3-
dimethyl-2,3,4,5-tetrahydro-1H-indolo[2,3-b]quinolin-1-one
(3c)
Yellow solid; mp: >300 ꢀC.
13C NMR (100 MHz, CDCl3) (
d ppm): 193.9, 193.7, 163.9, 155.6,
IR (KBr, v, cmꢁ1): 3069, 2956, 1666, 1619, 1600, 1518, 1441, 1305,
1264, 1161, 1015, 871, 763 cmꢁ1
;
154.4, 150.6, 140.9, 136.5, 136.1, 131.1, 131.0, 130.9, 129.4, 129.0,
129.0, 128.8, 123.1, 122.9, 122.9, 121.5, 119.2, 114.3, 113.6, 55.5, 50.4,
42.6, 33.2, 28.5, 27.9.
1H NMR (400 MHz, CDCl3) (
d ppm): 7.94 (d, c 2H, ArH), 7.71 (d,
J¼8.4 Hz, 1H, ArH), 7.49 (d, J¼6.8 Hz, 1H, ArH), 7.39 (t, J¼8.0 Hz, 1H,
ArH), 7.13 (t, J¼8.0 Hz, 1H, ArH), 7.13e6.97 (m, 2H, ArH), 6.94 (d,
J¼7.6 Hz, 3H, ArH), 4.03 (s, 3H, OCH3), 3.93 (s, 3H, OCH3), 3.85 (s, 3H,
OCH3), 2.76 (d, J¼10.4 Hz, 2H, CH2), 2.48 (d, J¼8.4 Hz, 2H, CH2), 1.11
(s, 3H, CH3), 1.09 (s, 3H, CH3).
HRMS (ESI) m/z: calcd for C31H26ClN2O3: 509.1632 [MþH]þ;
found: 509.1628.
4.8. 5-(4-Bromophenyl)-11-(4-methoxybenzoyl)-3,3-
dimethyl-2,3,4,5-tetrahydro-1H-indolo[2,3-b]quinolin-1-one
(3g)
13C NMR (100 MHz, CDCl3) (
d ppm): 194.0, 193.8, 163.9, 155.9,
154.5, 151.5, 150.4, 140.9, 130.9, 130.4, 129.4, 128.8, 122.8, 121.3,
119.8, 119.5, 119.2, 114.3, 114.3, 113.4, 112.0, 111.8, 110.2, 110.1, 56.2,
56.2, 55.5, 50.5, 42.4, 33.0, 28.5, 27.7.
Yellow solid, mp: >300 ꢀC.
IR (KBr, v, cmꢁ1): 2957, 1671, 1624, 1602, 1518, 1510, 1409, 1304,
HRMS (ESI) m/z: calcd for C33H31N2O5: 535.2227 [MþH]þ;
found: 535.2215.
1227, 1148, 1013, 854, 821 cmꢁ1
;
1H NMR (400 MHz, CDCl3) (
d
ppm): 7.93 (d, J¼8.4 Hz, 2H, ArH),
7.85(t, J¼8.4 Hz,2H,ArH), 7.66 (d, J¼8.0 Hz,1H,ArH), 7.48(d, J¼7.6Hz,
1H, ArH), 7.39 (t, J¼8.4 Hz, 2H, ArH), 7.24 (s,1H, ArH), 7.03 (t, J¼8.0 Hz,
1H, ArH), 6.94 (d, J¼8.4 Hz, 2H, ArH), 3.85 (s, 3H, OCH3), 2.71 (s, 2H,
CH2), 2.48 (d, J¼8.8 Hz, 2H, CH2), 1.11 (s, 3H, CH3), 1.09 (s, 3H, CH3).
4.5. 11-(4-Methoxybenzoyl)-3,3-dimethyl-5-phenyl-2,3,4,5-
tetrahydro-1H-indolo[2,3-b]quinolin-1-one (3d)
Yellow solid; mp: >300 ꢀC.
13C NMR (100 MHz, CDCl3) (
d ppm): 193.9, 193.7, 163.9, 155.5,
IR (KBr, v, cmꢁ1): 2950, 1670, 1621, 1599, 1523, 1505, 1412, 1337,
154.4, 150.6, 141.0, 136.7, 134.1, 133.9, 130.9, 129.3, 129.1, 129.03,
124.7, 123.1, 122.9, 121.5, 119.2, 114.3, 113.6, 55.5, 50.4, 42.6, 33.2,
28.5, 27.9.
1293, 1246, 1166, 1024, 857, 766 cmꢁ1
;
1H NMR (400 MHz, CDCl3) (
d
ppm): 7.95 (d, J¼7.2 Hz, 2H, ArH),
HRMS (ESI) m/z: calcd for C31H26BrN2O3: 553.1121 [MþH]þ;
found: 553.1159.
7.80e7.69 (m, 2H, ArH), 7.66 (d, J¼7.6 Hz, 2H, ArH), 7.50 (s, 2H, ArH),
7.38 (s, 2H, ArH), 7.04 (t, J¼7.6 Hz, 1H, ArH), 6.95 (d, J¼8.4 Hz, 2H,
ArH), 3.86 (s, 3H, OCH3), 2.71 (s, 2H, CH2), 2.48 (d, J¼8.4 Hz, 2H,
CH2), 1.10 (s, 3H, CH3), 1.08 (s, 3H, CH3).
4.9. 5-(2-Bromophenyl)-11-(4-methoxybenzoyl)-3,3-
dimethyl-2,3,4,5-tetrahydro-1H-indolo[2,3-b]quinolin-1-one
(3h)
13C NMR (100 MHz, CDCl3) (
d ppm): 193.9, 193.8, 163.9, 155.7,
154.5,150.9,141.0, 137.9, 130.9,130.8,130.6,130.3,129.5, 128.8,127.6,
127.4, 122.8, 121.3, 119.2, 114.3, 113.5, 55.5, 50.5, 42.6, 33.1, 28.5, 27.9.
HRMS (ESI) m/z: calcd for C31H27N2O3: 475.2022 [MþH]þ;
found: 475.2029.
Yellow solid; mp: >300 ꢀC.
IR (KBr, v, cmꢁ1): 2948, 1667, 1624, 1599, 1509, 1439, 1412, 1305,
1257, 1222, 1166, 1022, 856, 774, 765 cmꢁ1
;
4.6. 5-(4-Fluorophenyl)-11-(4-methoxybenzoyl)-3,3-
dimethyl-2,3,4,5-tetrahydro-1H-indolo[2,3-b]quinolin-1-one
(3e)
1H NMR (400 MHz, CDCl3) (
d
ppm): 7.92 (t, J¼7.2 Hz, 3H, ArH),
7.71e7.63 (m, 2H, ArH), 7.61e7.46 (m, 3H, ArH), 7.39 (t, J¼7.6 Hz, 1H,
ArH), 7.04 (t, J¼7.6 Hz, 1H, ArH), 6.94 (t, J¼7.6 Hz, 2H, ArH), 3.85 (s,
3H, OCH3), 2.71e2.55 (m, 2H, CH2), 2.49 (d, J¼9.6 Hz, 2H, CH2), 1.12
(s, 3H, CH3), 1.10 (s, 3H, CH3).
Yellow solid, mp: >300 ꢀC.
IR (KBr, v, cmꢁ1): 3416, 2951, 1671, 1620, 1601, 1575, 1510, 1411,
13C NMR (100 MHz, CDCl3) (
d ppm) 193.8, 193.7, 163.9, 163.8,
1248, 1153, 1026, 860, 848, 764, 625 cmꢁ1
.
150.7,140.8,137.1,134.7,134.5,131.9,130.9,129.9,129.6,129.4,129.2,
129.0,122.9,121.4,119.2,114.4,114.3, 55.5, 50.6, 42.0, 33.0, 29.2, 27.5.
HRMS (ESI) m/z: calcd for C31H26BrN2O3: 553.1121 [MþH]þ;
found: 553.1113.
1H NMR (400 MHz, CDCl3) (
d
ppm): 7.94 (d, J¼7.7 Hz, 1H, ArH),
7.66 (d, J¼8.2 Hz, 1H, ArH), 7.50 (s, 1H, ArH), 7.46e7.33 (m, 2H, ArH),
7.03 (s, 1H, ArH), 6.95 (d, J¼8.2 Hz, 1H, ArH), 3.86 (s, 3H, OCH3), 2.71

1008
M.-Y. Li et al. / Tetrahedron 70 (2014) 1004e1010
4.10. 5-(2-Iodophenyl)-11-(4-methoxybenzoyl)-3,3-dimethyl-
2,3,4,5-tetrahydro-1H-indolo[2,3-b]quinolin-1-one (3i)
(d, J¼8.4 Hz, 2H, CH2), 2.39 (s, 3H, CH3), 1.14 (s, 3H, CH3), 1.12 (s,
3H, CH3).
13C NMR (100 MHz, CDCl3) (
d ppm): 194.7, 193.9, 154.6, 150.4,
Yellow solid; mp>300 ꢀC.
150.3, 144.4, 140.8, 133.9, 131.8, 130.7, 130.5, 129.8, 129.7, 129.0,
128.7, 128.7, 128.6, 123.0, 122.8, 121.4, 119.3, 113.8, 97.5, 50.5, 42.2,
33.0, 29.2, 28.8, 28.2, 27.8, 21.8.
IR (KBr, v, cmꢁ1): 2948, 1668, 1623, 1600, 1523, 1507, 1412, 1338,
1294, 1242, 1166, 1022, 856, 743 cmꢁ1
.
1H NMR (400 MHz, CDCl3) (
d
, ppm): 8.16 (d, J¼7.2 Hz, 1H, ArH),
HRMS (ESI) m/z: calcd for C31H26IN2O2: 585.1039 [MþH]þ;
found: 585.1038.
7.98e7.86 (m, 2H, ArH), 7.75e7.65 (m, 2H, ArH), 7.50 (m, 2H, ArH),
7.40 (s, 2H, ArH), 7.05 (d, J¼6.8 Hz, 1H, ArH), 6.93 (t, J¼7.4 Hz, 2H,
ArH), 3.84 (s, 3H, OCH3), 2.63 (m, 2H, CH2), 2.49 (d, J¼10.0 Hz, 2H,
CH2), 1.15 (s, 3H, CH3), 1.13 (s, 3H, CH3).
4.14. 3,3,8-Trimethyl-11-(4-methylbenzoyl)-5-(p-tolyl)-
2,3,4,5-tetrahydro-1H-indolo[2,3-b]quinolin-1-one (3m)
13C NMR (100 MHz, CDCl3) (
d ppm): 193.9, 193.7, 163.9, 163.8,
Yellow solid; mp: >300 ꢀC.
154.7, 154.6, 150.5, 141.1, 140.8, 131.8, 130.9, 130.5, 129.0, 128.8,
128.6, 122.9, 121.4, 119.3, 114.4, 114.2, 97.5, 55.5, 50.6, 42.2, 32.96,
29.3, 27.8.
IR (KBr, v, cmꢁ1): 2957, 1670, 1664, 1621, 1604, 1524, 1468, 1416,
1370, 1317, 1239, 1152, 1012, 820, 753 cmꢁ1
.
HRMS (ESI) m/z: calcd for C31H26IN2O3: 601.0988 [MþH]þ;
found: 601.0963.
1H NMR (400 MHz, CDCl3) (
d
, ppm): 7.86 (d, J¼7.6 Hz, 2H, ArH),
7.56 (d, J¼8.4 Hz, 1H, ArH), 7.49 (t, J¼8.4 Hz, 2H, ArH), 7.37 (d,
J¼8.4 Hz, 1H, ArH), 7.28 (s, 2H, ArH), 7.25e7.15 (m, 3H, ArH), 2.71 (s,
2H, CH2), 2.52 (s, 3H, CH3), 2.45 (d, J¼5.6 Hz, 2H, CH2), 2.40 (s, 3H,
CH3), 2.27 (s, 3H, CH3), 1.09 (s, 3H, CH3), 1.07 (s, 3H, CH3).
HRMS (ESI) m/z: calcd for C33H31N2O3: 487.2386 [MþH]þ;
found: 487.2384.
4.11. 5-(4-Bromophenyl)-3,3-dimethyl-11-(4-methylbenzoyl)-
2,3,4,5-tetrahydro-1H-indolo[2,3-b]quinolin-1-one (3j)
Yellow solid; mp: >300 ꢀC.
IR (KBr, v, cmꢁ1): 2949, 1665, 1620, 1579, 1567, 1487, 1366, 1327,
1280, 1109, 885, 825, 758 cmꢁ1
.
4.15. 5-(4-Bromophenyl)-3,3,8-trimethyl-11-(4-
methylbenzoyl)-2,3,4,5-tetrahydro-1H-indolo[2,3-b]quinolin-
1-one (3n)
1H NMR (400 MHz, CDCl3) (
d
ppm): 7.86 (d, J¼8.0 Hz, 2H,
ArH), 7.74e7.61 (m, 3H, ArH), 7.53e7.43 (m, 2H, ArH), 7.40 (t,
J¼7.2 Hz, 1H, ArH), 7.35e7.30 (m, 1H, ArH), 7.27 (s, 1H, ArH), 7.25
(s, 1H, ArH), 7.03 (t, J¼7.6 Hz, 1H, ArH), 2.71 (s, 2H, CH2), 2.48 (d,
J¼7.6 Hz, 2H, CH2), 2.41 (s, 3H, CH3), 1.11 (s, 3H, CH3), 1.09 (s, 3H,
CH3).
Yellow solid; mp: >300 ꢀC.
IR (KBr, v, cmꢁ1): 2952, 1674, 1671, 1620, 1604, 1514, 1440, 1402,
1336, 1224, 1142, 1012, 848, 846, 776, 763 cmꢁ1
.
13C NMR (100 MHz, CDCl3) (
d ppm): 194.7, 193.8, 155.5, 154.4,
1HNMR(400MHz, CDCl3)(
d
, ppm):7.84(t,J¼7.2Hz, 4H,ArH), 7.57
150.4, 144.5, 140.8, 136.6, 134.1, 133.9, 133.8, 129.7, 129.3, 129.1,
128.6, 124.7, 123.2, 122.8, 121.5, 119.2, 113.6, 50.3, 42.6, 33.2, 28.5,
27.9, 21.8.
(d, J¼8.4 Hz, 1H, ArH), 7.41 (d, J¼8.4 Hz, 1H, ArH), 7.27 (s, 2H, ArH),
7.26e7.18 (m, 3H, ArH), 2.70 (s, 2H, CH2), 2.46 (d, J¼¼5.2 Hz, 2H, CH2),
2.41 (s, 3H, CH3), 2.27 (s, 3H, CH3), 1.10 (s, 3H, CH3), 1.08 (s, 3H, CH3).
HRMS (ESI) m/z: calcd for C31H26BrN2O2: 537.1178 [MþH]þ;
found: 537.1187.
13C NMR (100 MHz, CDCl3)(
d ppm):194.8,193.7,155.2,152.5,150.2,
144.4, 140.5, 136.7, 134.0, 133.9, 131.0, 130.5, 129.7, 129.3, 129.1, 128.7,
124.6, 123.2, 122.8, 118.8, 113.5, 50.4, 42.6, 33.1, 28.5, 27.9, 21.8, 21.5.
HRMS (ESI) m/z: calcd for C32H28BrN2O2: 551.1334 [MþH]þ;
found: 551.1349.
4.12. 5-(2-Bromophenyl)-3,3-dimethyl-11-(4-methylbenzoyl)-
2,3,4,5-tetrahydro-1H-indolo[2,3-b]quinolin-1-one (3k)
Yellow solid; mp: >300 ꢀC.
IR (KBr, v, cmꢁ1): 2952, 1674, 1669, 1620, 1604, 1513, 1440, 1404,
4.16. 5-(4-Chlorophenyl)-11-(4-fluorobenzoyl)-3,3-dimethyl-
2,3,4,5-tetrahydro-1H-indolo[2,3-b]quinolin-1-one (3o)
1336, 1224, 1144, 1012, 856, 846, 776, 763 cmꢁ1
.
1H NMR (400 MHz, CDCl3) (
d, ppm): 7.92 (t, J¼6.8 Hz, 1H, ArH),
Yellow solid; mp: >300 ꢀC.
7.88e7.79 (m, 2H, ArH), 7.68 (t, J¼8.8 Hz, 2H, ArH), 7.57 (t, J¼8.0 Hz,
1H, ArH), 7.54e7.45 (m, 2H, ArH), 7.40 (t, J¼7.6 Hz, 1H, ArH), 7.28 (s,
1H, ArH), 7.24 (s, 1H, ArH), 7.04 (t, J¼7.6 Hz, 1H, ArH), 2.77e2.54 (m,
2H, CH2), 2.48 (d, J¼7.2 Hz, 2H, CH2), 2.40 (s, 3H, CH3), 1.12 (s, 3H,
CH3), 1.10 (s, 3H, CH3).
IR (KBr, v, cmꢁ1): 2959, 1672, 1619, 1597, 1521, 1505, 1434, 1412,
1305, 1292, 1228, 1147, 1075, 858, 765, 751 cmꢁ1
.
1H NMR (400 MHz, CDCl3) (
d, ppm): 7.99 (m, 2H, ArH), 7.72 (d,
J¼7.6 Hz, 1H, ArH), 7.50 (t, J¼7.2 Hz, 2H, ArH), 7.47e7.34 (m, 3H,
ArH), 7.24 (s, 1H, ArH), 7.15 (t, J¼8.4 Hz, 2H, ArH), 7.05 (t, J¼7.6 Hz,
1H, ArH), 2.75 (d, J¼4.4 Hz, 2H, CH2), 2.49 (d, J¼6.4 Hz, 2H, CH2),1.10
(s, 3H, CH3), 1.08 (s, 3H, CH3).
13C NMR (100 MHz, CDCl3) (
d ppm): 194.7, 193.9, 150.7, 144.5,
134.7, 134.5, 133.8, 131.9, 129.9, 129.8, 129.7, 129.4, 129.2, 129.0,
128.6, 122.9, 122.8, 121.6, 121.4, 119.2, 50.5, 41.9, 41.8, 33.0, 30.9,
29.1, 28.7, 27.9, 27.5, 21.8.
HRMS (ESI) m/z: calcd for C30H23ClFN2O2: 497.1432 [MþH]þ;
found: 497.1431.
HRMS (ESI) m/z: calcd for C31H26BrN2O2: 537.1178 [MþH]þ;
found: 537.1179.
4.17. 5-(4-Bromophenyl)-11-(4-fluorobenzoyl)-3,3-dimethyl-
2,3,4,5-tetrahydro-1H-indolo[2,3-b]quinolin-1-one (3p)
4.13. 5-(2-Iodophenyl)-3,3-dimethyl-11-(4-methylbenzoyl)-
2,3,4,5-tetrahydro-1H-indolo[2,3-b]quinolin-1-one (3l)
Yellow solid; mp: >300 ꢀC.
Yellow solid; mp: >300 ꢀC.
IR (KBr, v, cmꢁ1): 2959, 1671, 1619, 1597, 1522, 1505, 1434, 1412,
IR (KBr, v, cmꢁ1): 2951, 1671, 1662, 1620, 1603, 1519, 1440, 1403,
1304, 1292, 1224, 1147, 1075, 859, 765, 755 cmꢁ1
.
1292, 1224, 1178, 1145, 1024, 856, 774, 761 cmꢁ1
.
1H NMR (400 MHz, CDCl3) (
d, ppm) :8.06e7.89 (m, 2H, ArH), 7.85
1H NMR (400 MHz, CDCl3) (
d
, ppm): 8.14 (d, J¼7.6 Hz, 1H, ArH),
(t, J¼7.6 Hz, 2H, ArH), 7.67 (d, J¼8.0 Hz, 1H, ArH), 7.49e7.32 (m, 4H,
ArH), 7.14 (t, J¼7.6 Hz, 1H, ArH), 7.09e6.99 (m, 2H, ArH), 2.72 (s, 2H,
CH2), 2.49 (d, J¼7.2 Hz, 2H, CH2), 1.10 (s, 6H, CH3). HRMS (ESI) m/z:
calcd for C30H23BrF2N2O2: 541.0927 [MþH]þ; found: 541.0901.
7.84 (t, J¼8.8 Hz, 2H, ArH), 7.69 (s, 2H, ArH), 7.58e7.44 (m, 2H,
ArH), 7.39 (d, J¼5.6 Hz, 2H, ArH), 7.27 (s, 1H, ArH), 7.24e7.16 (m,
1H, ArH), 7.04 (t, J¼7.2 Hz, 1H, ArH), 2.77e2.52 (m, 2H, CH2), 2.47

M.-Y. Li et al. / Tetrahedron 70 (2014) 1004e1010
1009
4.18. 11-(4-Fluorobenzoyl)-5-(2-iodophenyl)-3,3-dimethyl-
4.22. 5-(4-Bromophenyl)-11-(4-methylbenzoyl)-2,3,4,5-
2,3,4,5-tetrahydro-1H-indolo[2,3-b]quinolin-1-one (3q)
tetrahydro-1H-indolo[2,3-b]quinolin-1-one (3u)
Yellow solid; mp: >300 ꢀC.
Yellow solid; mp: >300 ꢀC.
IR (KBr, v, cmꢁ1): 2957, 1670, 1614, 1597, 1524, 1505, 1434, 1416,
IR (KBr, v, cmꢁ1): 2963, 1667, 1638, 1619, 1604, 1520, 1505, 1413,
1304, 1290, 1224, 1147, 1075, 859, 765, 748 cmꢁ1
.
1340, 1287, 1228, 1174, 1069, 1008, 839, 762 cmꢁ1
1H NMR (400 MHz, CDCl3) (
, ppm) 7.93e7.77 (m, 4H, ArH), 7.66
.
1H NMR (400 MHz, CDCl3) (
d
, ppm): 8.15 (d, J¼7.6 Hz, 1H, ArH),
d
8.03e7.87 (m, 2H, ArH), 7.79e7.63 (m, 2H, ArH), 7.61e7.45 (m, 2H,
ArH), 7.45e7.36 (m, 2H, ArH), 7.20e7.10 (m, 1H, ArH), 7.06 (t,
J¼8.0 Hz, 1H, ArH), 6.94 (d, J¼8.0 Hz, 1H, ArH), 2.76e2.55 (m, 2H,
CH2), 2.55e2.42 (m, 2H, CH2), 1.15 (s, 3H, CH3), 1.13 (s, 3H, CH3).
HRMS (ESI) m/z: calcd for C30H23FIN2O2: 589.0788 [MþH]þ;
found: 589.0781.
(d, J¼8.0 Hz, 1H, ArH), 7.46 (d, J¼7.6 Hz, 1H, ArH), 7.44e7.35 (m, 2H,
ArH), 7.33e7.28 (m, 2H, ArH), 7.25 (s, 1H, ArH), 7.02 (t, J¼7.6 Hz, 1H,
ArH), 2.85 (m, 2H, CH2), 2.60 (m, 2H, CH2), 2.40 (s, 3H, CH3),
2.25e1.94 (m, 2H, CH2).
13C NMR (100 MHz, CDCl3) (
d ppm): 194.7, 193.8, 155.2, 154.5,
152.0, 144.5, 141.2, 136.7, 134.0, 133.8, 129.7, 129.3, 129.1, 128.8,
124.7, 123.4, 122.9, 122.8, 121.5, 119.2, 114.6, 36.9, 29.2, 21.8, 21.5.
HRMS (ESI) m/z: calcd for C29H22BrN2O2: 509.0865 [MþH]þ;
found: 509.0848.
4.19. 11-(4-Chlorobenzoyl)-3,3-dimethyl-5-(p-tolyl)-2,3,4,5-
tetrahydro-1H-indolo[2,3-b]quinolin-1-one (3r)
4.23. 5-(4-Bromophenyl)-8-methyl-11-(4-methylbenzoyl)-
2,3,4,5-tetrahydro-1H-indolo[2,3-b]quinolin-1-one (3v)
Yellow solid; mp: >300 ꢀC.
IR (KBr, v, cmꢁ1): 2950, 1676, 1664, 1623, 1604, 1513, 1440, 1404,
1359, 1304, 1231, 1176, 1104, 1012, 846, 776 cmꢁ1
.
Yellow solid; mp: >300 ꢀC.
1H NMR (400 MHz, CDCl3) (
d, ppm): 7.90 (d, J¼8.0 Hz, 2H, ArH),
IR (KBr, v, cmꢁ1): 2950, 1672, 1668, 1605, 1520, 1487, 1467, 1409,
7.69 (d, J¼8.0 Hz, 1H, ArH), 7.50 (t, J¼8.4 Hz, 2H, ArH), 7.48e7.42 (m,
3H, ArH), 7.41e7.34 (m, 2H, ArH), 7.24 (d, J¼7.6 Hz, 1H, ArH), 7.04 (t,
J¼7.6 Hz, 1H, ArH), 2.73 (s, 2H, CH2), 2.53 (s, 3H, CH3), 2.47 (d,
J¼7.2 Hz, 2H, CH2), 1.09 (s, 3H, CH3), 1.07 (s, 3H, CH3).
1327, 1285, 1237, 1199, 1124, 1045, 856, 830, 773 cmꢁ1
.
1H NMR (400 MHz, CDCl3) (
d, ppm): 7.95e7.75 (m, 4H, ArH), 7.55
(d, J¼8.0 Hz, 1H, ArH), 7.42 (d, J¼8.0 Hz, 1H, ArH), 7.30 (s, 2H, ArH),
7.26e7.15 (m, 3H, ArH), 2.84 (d, J¼5.6 Hz, 2H, CH2), 2.60 (d,
J¼6.4 Hz, 2H, CH2), 2.41 (s, 3H, CH3), 2.27 (s, 3H, CH3), 2.17 (s, 2H,
CH2).
13C NMR (100 MHz, CDCl3) (
d ppm): 194.1, 194.0, 155.8, 154.6,
151.3, 140.6, 139.9, 135.1, 134.8, 131.5, 131.3, 129.9, 129.4, 129.1, 127.1,
126.9,123.1,122.5,121.4,119.5,113.3, 50.3, 42.5, 33.2, 28.4, 28.0, 21.5.
HRMS (ESI) m/z: calcd for C29H38NO8: 528.2597 [MþH]þ; found:
528.2546.
HRMS (ESI) m/z: calcd for C30H24BrN2O2: 523.1016 [MþH]þ;
found: 523.0997.
4.24. 5-(4-Fluorophenyl)-11-(4-methoxybenzoyl)-2,3,4,5-
tetrahydro-1H-indolo[2,3-b]quinolin-1-one (3w)
4.20. 5-(4-Bromophenyl)-11-(4-chlorobenzoyl)-3,3-dimethyl-
2,3,4,5-tetrahydro-1H-indolo[2,3-b]quinolin-1-one (3s)
Yellow solid; mp: >300 ꢀC.
Yellow solid; mp: >300 ꢀC.
IR (KBr, v, cmꢁ1): 2957, 1670, 1600, 1573, 1521, 1510, 1442, 1409,
IR (KBr, v, cmꢁ1): 2952, 1674, 1664, 1620, 1604, 1514, 1440, 1412,
1275, 1228, 1169, 857, 763 cmꢁ1
.
1354, 1304, 1230, 1176, 1104, 1012, 864, 776 cmꢁ1
.
1H NMR (400 MHz, CDCl3) (
d
, ppm): 7.95 (d, J¼8.0 Hz, 2H, ArH),
1H NMR (400 MHz, CDCl3) (
d, ppm): 7.93e7.79 (m, 4H, ArH),
7.68 (d, J¼8.0 Hz, 1H, ArH), 7.52 (s, 1H, ArH), 7.46 (d, J¼7.6 Hz, 1H,
ArH), 7.40 (s, 4H, ArH), 7.03 (t, J¼7.6 Hz, 1H, ArH), 6.95 (d, J¼8.4 Hz,
1H, ArH), 3.86 (s, 3H, OCH3), 2.86 (d, J¼5.6 Hz, 2H, CH2), 2.62 (d,
J¼8.0 Hz, 2H, CH2), 2.31e2.07 (m, 2H, CH2).
7.68 (d, J¼8.0 Hz, 1H, ArH), 7.44 (d, J¼8.4 Hz, 3H, ArH), 7.41e7.36
(m, 2H, ArH), 7.25 (s, 1H, ArH), 7.06 (t, J¼7.6 Hz, 1H, ArH), 2.71 (s,
2H, CH2), 2.47 (d, J¼8.0 Hz, 2H, CH2), 1.10 (s, 3H, CH3), 1.08 (s, 3H,
CH3).
HRMS (ESI) m/z: calcd for C29H22FN2O3: 465.1614 [MþH]þ;
found: 465.1613.
13C NMR (100 MHz, CDCl3) (
d ppm): 193.9, 193.8, 155.4, 154.5,
150.6, 140.0, 139.8, 136.5, 134.6, 134.1, 134.0, 129.8, 129.4, 129.2,
129.0, 124.8, 123.3, 122.6, 121.7, 119.4, 113.5, 50.3, 42.5, 33.2, 28.4,
27.9.
4.25. 5-(4-Chlorophenyl)-11-(4-methoxybenzoyl)-2,3,4,5-
tetrahydro-1H-indolo[2,3-b]quinolin-1-one (3x)
HRMS (ESI) m/z: calcd for C30H23BrClN2O2: 557.0626 [MþH]þ;
found: 557.0624.
Yellow solid; mp: >300 ꢀC.
IR (KBr, v, cmꢁ1): 2957, 1672, 1600, 1573, 1521, 1514, 1442, 1400,
4.21. 5-(4-Chlorophenyl)-11-(4-methylbenzoyl)-2,3,4,5-
tetrahydro-1H-indolo[2,3-b]quinolin-1-one (3t)
1276, 1230, 1169, 857, 768 cmꢁ1
.
1H NMR (400 MHz, CDCl3) (
d
, ppm): 7.94 (d, J¼8.4 Hz, 2H), 7.67
(t, J¼7.2 Hz, 3H), 7.47 (t, J¼7.2 Hz, 2H), 7.43e7.31 (m, 2H), 7.03 (t,
J¼7.2 Hz, 1H), 6.94 (d, J¼8.4 Hz, 2H), 3.85 (s, 3H), 2.86 (s, 2H), 2.62
(d, J¼8.0 Hz, 2H), 2.17 (s, 2H).
Yellow solid; mp: >300 ꢀC.
IR (KBr, v, cmꢁ1): 2952, 1674, 1668, 1619, 1604, 1513, 1440, 1404,
1367, 1304, 1224, 1176, 1144, 1012, 846, 776 cmꢁ1
.
HRMS (ESI) m/z: calcd for C29H22ClN2O3: 481.1319 [MþH]þ;
found: 481.1330.
1H NMR (400 MHz, CDCl3) (
d, ppm): 7.87 (d, J¼8.0 Hz, 2H, ArH),
7.75e7.58 (m, 3H, ArH), 7.53e7.43 (m, 2H, ArH), 7.44e7.32 (m, 2H,
ArH), 7.27 (s, 1H, ArH), 7.25 (s, 1H, ArH), 7.03 (t, J¼7.6 Hz, 1H, ArH),
2.86 (m, 2H, CH2), 2.61 (m, 2H, CH2), 2.40 (s, 3H, CH3), 2.17 (t,
J¼7.6 Hz, 2H, CH2).
4.26. 5-(4-Bromophenyl)-11-(4-methoxybenzoyl)-2,3,4,5-
tetrahydro-1H-indolo[2,3-b]quinolin-1-one (3y)
13C NMR (100 MHz, CDCl3) (
d
ppm): 194.8, 193.8, 152.1, 144.5,
Yellow solid; mp: >300 ꢀC.
141.2, 136.6,136.1, 133.8, 131.0, 130.8, 129.7, 129.1, 129.0,128.8,128.7,
123.4, 122.9, 122.8, 121.5, 119.2, 114.6, 36.9, 29.2, 21.8, 21.5.
HRMS (ESI) m/z: calcd for C29H22ClN2O2: 465.1370 [MþH]þ;
found: 465.1374.
IR (KBr, v, cmꢁ1): 2957, 1670, 1609, 1573, 1525, 1520, 1442, 1407,
1268, 1232, 1172, 855, 768 cmꢁ1
.
1H NMR (400 MHz, CDCl3) (
d, ppm): 7.94 (d, J¼8.4 Hz, 2H, ArH),
7.82e7.56 (m, 3H, ArH), 7.54e7.43 (m, 2H, ArH), 7.42e7.30 (m, 2H,

1010
M.-Y. Li et al. / Tetrahedron 70 (2014) 1004e1010
7. (a) Chen, Y. L.; Chung, C. H.; Chen, I. L.; Chen, P. H.; Jeng, H. Y. Bioorg. Med. Chem.
2001, 10, 2705e2712; (b) Alajarin, M.; Molina, P.; Vidal, A. J. Nat. Prod. 1997, 60,
747e748; (c) Peczynska-Czoch, W.; Pognan, F.; Kaczmarek, L.; Boratynski, J. J.
Med. Chem. 1994, 37, 3503e3510.
ArH), 7.03(t, J¼7.6Hz,1H,ArH), 6.94 (d, J¼8.8Hz,2H,ArH),3.85(s, 3H,
OCH3), 2.86 (m, 2H, CH2), 2.62 (m, 2H, CH2), 2.39e1.95 (m, 2H, CH2).
13C NMR (100 MHz, CDCl3) (
d ppm): 193.7, 193.7, 163.9, 155.1,
8. Gabriel, S.; Eschenbach, G. Ber. Dtsch. Chem. Ges. 1897, 30, 3022e3037.
9. (a) Lawson, W.; Perkin, W. H.; Robinson, R. J. Chem. Soc. Trans. 1924, 125,
626e657; (b) Holt, S. J.; Petrov, V. J. Chem. Soc. 1948, 922e924.
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53, 4751e4753.
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Sayed, I.; Egan, T. J.; Inokuchi, T. Eur. J. Med. Chem. 2013, 64, 498e511; (b) Ka-
dam, H. K.; Parvatkar, P. T.; Tilve, S. G. Synthesis 2012, 1339e1342; (c) Parvatkar,
P. T.; Ajay, A. K.; Bhat, M. K.; Parameswaran, P. S.; Tilve, S. G. Med. Chem. Res.
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Bioorg. Med. Chem. 2004, 12, 6539e6546.
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Sridharan, V.; Ribelles, P.; Estevez, V.; Villacampa, M.; Ramos, M. T.; Perumal, P.
T.; Menendez, J. C. Chem.dEur. J. 2012, 18, 5056e5063; (c) Rajkumar, S.;
Shankland, K.; Brown, G. D.; Cobb, A. J. A. Chem. Sci. 2012, 3, 584e588; (d) Hong,
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152.0, 136.6, 134.0, 133.8, 131.0, 129.4, 129.3, 129.1, 124.7, 122.98,
122.8, 121.6, 119.2, 114.6, 114.3, 55.5, 37.0, 32.9, 29.2, 21.5.
HRMS (ESI) m/z: calcd for C29H22BrN2O3: 525.0808 [MþH]þ;
found: 525.0798.
4.27. 5-(2-Iodophenyl)-11-(4-methoxybenzoyl)-2,3,4,5-
tetrahydro-1H-indolo[2,3-b]quinolin-1-one (3z)
Yellow solid; mp: >300 ꢀC.
IR (KBr, v, cmꢁ1): 2957, 1672, 1610, 1573, 1527, 1520, 1486, 1407,
1258, 1232, 1172, 855, 744 cmꢁ1
.
d
1H NMR (400 MHz, CDCl3) (
, ppm): 8.14 (d, J¼7.2 Hz, 1H, ArH),
7.94 (s, 2H, ArH), 7.77e7.60 (m, 2H, ArH), 7.51 (s, 2H, ArH), 7.39 (d,
J¼7.2 Hz, 2H, ArH), 7.05 (d, J¼7.2 Hz,1H, ArH), 6.94 (s, 2H, ArH), 3.85
(s, 3H, OCH3), 2.78 (s, 2H, CH2), 2.64 (s, 2H, CH2), 2.18 (s, 2H, CH2).
13C NMR(100 MHz,CDCl3)(
dppm):194.0,193.8,163.9,154.7,154.3,
152.1, 141.1, 141.0, 140.7, 131.8, 131.7, 131.0, 130.7, 129.4, 129.0, 128.8,
128.6, 122.9, 121.4, 119.3, 114.4, 114.2, 97.5, 55.5, 37.1, 31.0, 28.7, 21.6.
HRMS (ESI) m/z: calcd for C29H22IN2O3: 573.0675 [MþH]þ;
found: 573.0663.
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Domling, A.; Wang, W.; Wang, K. Chem. Rev. 2012, 112, 3083e3135; (c) Fustero, S.;
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Sanchez-Rosello, M.; Barrio, P.; Simon-Fuentes, A. Chem. Rev. 2011, 111,
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Acknowledgements
15. (a) Jiang, B.; Li, C.; Shi, F.; Tu, S.-J.; Kaur, P.; Wever, W.; Li, G. J. Org. Chem. 2010,
75, 2862e2865; (b) Jiang, B.; Tu, S.-J.; Kaur, P.; Wever, W.; Li, G. J. Am. Chem. Soc.
2009, 131, 11660e11661; (c) Jiang, B.; Yi, M.-S.; Tu, M.-S.; Wang, S.-L.; Tu, S.-J.
Adv. Synth. Catal. 2012, 354, 2504e2510.
16. (a) Ma, N.; Jiang, B.; Zhang, G.; Tu, S.-J.; Wever, W.; Li, G. Green. Chem. 2010, 12,
1357e1361; (b) Jiang, B.; Yi, M.-S.; Shi, F.; Tu, S.-J.; Pindi, S.; McDowell, P.; Li, G.
Chem. Commun. 2012, 808e810; (c) Jiang, B.; Feng, B.-M.; Wang, S.-L.; Tu, S.-J.;
Li, G. Chem.dEur. J. 2012, 18, 9823e9826.
We are grateful for financial support from the National Science
Foundation of China (21072163, 21232004, 21272095, and
21102124), PAPD of Jiangsu Higher Education Institutions, the NSF
of Jiangsu Education Committee (11KJB150016), and Doctoral Re-
search Foundation of Xuzhou Normal Univ. (XZNU, No. 10XLR20).
17. (a) Suresh Babu, A. R.; Raghunathan, R. Tetrahedron Lett. 2007, 48, 6809e6813;
(b) Suresh Babu, A. R.; Raghunathan, R. Synth. Commun. 2008, 38, 1433e1438;
(c) Natarajan, A.; Raghavachary, R. Synth. Commun. 2011, 41, 2747e2755; (d)
Paponov, B. V.; Shishkin, O. V.; Shishkina, S. V.; Zubatyuk, R. I.; Kalyuzhny, A. L.;
Musatov, V. I. Russ. Chem. Bull. 2008, 57, 622e631.
Supplementary data
Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.tet.2013.11.022.
18. Han, Y.; Sun, Y.; Sun, J.; Yan, C.-G. Tetrahedron 2012, 68, 8256e8260.
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tinck, A. J. J. Nat. Prod. 1997, 60, 688e691; (c) Peczynska-Czoch, W.; Pognan, F.;
Kaczmarek, L.; Boratynski, J. J. Med. Chem. 1994, 37, 3503e3510; (d) Kaczmarek,
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References and notes
1. Moquin, C.; Guyot, M. Tetrahedron Lett. 1984, 25, 5047e5048.
2. Moquin-Pattey, C.; Guyot, M. Tetrahedron 1989, 45, 3445e3450.
3. Abas, S. A.; Hossain, M. B.; van der Helm, D.; Schmitz, F. J.; Laney, M.; Cabuslay,
R.; Schatzman, R. C. J. Org. Chem. 1996, 61, 2709e2712.
4. Kim, J. S.; Shin-ya, K.; Furihata, K.; Hayakawa, Y.; Seto, H. Tetrahedron Lett. 1997,
38, 3431e3434.
5. (a) Molina, P.; Alajarin, M.; Vidal, A. J. Chem. Soc., Chem. Commun. 1990,
1277e1279; (b) Molina, P.; Alajarin, M.; Vidal, A.; Sanchez-Andrada, P. J. Org.
Chem. 1992, 57, 929e939; (c) Wang, T.-C.; Lee, K.-H.; Chen, Y.-L.; Liou, S.-S.;
Tzeng, C.-C. Bioorg. Med. Chem. 1998, 8, 2773e2776; (d) Sundaram, G. S. M.;
Venkatesh, C.; Syam Kumar, U. K.; Junjappa, H.; Ila, H. J. Org. Chem. 2004, 69,
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6. (a) Cimanga, K.; de Bruyne, T.; Pieters, L.; Claeys, M.; Vlietinck, A. Tetrahedron
Lett. 1996, 37, 1703e1706; (b) Sharaf, M. H. M.; Schiff, P. L.; Tackie, A. N.; Phoebe,
C. H.; Martin, G. E. J. Heterocycl. Chem. 1996, 33, 239e243.
20. Crystal data for 3w:
C
32H28FN3O4, crystal dimension 0.42ꢂ0.18ꢂ0.14 mm,
ꢁ ꢁ ꢁ
3
Monoclinic, space group Cc, a¼14.4352(13) A, b¼26.027(3) A, c¼9.3423(8) A,
ꢀ
ꢁ
a
¼90ꢀ,
b
¼129.925(2)ꢀ,
g
¼90 , V¼2691.7(4) A , Mr¼537.57, Z¼4, Dc¼1.327 Mg/
m3,
g
¼0.71073 A,
m
(Mo Ka)¼0.093 mmꢁ1, F(000)¼1128, R¼0.0631, wR2¼0.1535,
ꢁ
3
ꢁ
S¼1.044, largest diff. Peak and hole: 0.346 and ꢁ0.245 e/A
21. (a) Yoneda, F.; Yano, T.; Higuchi, M.; Koshiro, A. Chem. Lett. 1979, 155e158; (b)
Devi, I.; Kumarb, B. S. D.; Bhuyana, P. J. Tetrahedron Lett. 2003, 44, 8307e8310;
(c) Evdokimov, N. M.; Magedov, I. V.; Kireev, A. S.; Kornienko, A. Org. Lett. 2006,
8, 899e902; (d) Tu, S.; Jiang, B.; Zhang, Y.; Jia, R.; Zhang, J.; Yao, C.; Shi, F. Org.
Biomol. Chem. 2007, 5, 355e359.