A stereoselective Povarov reaction leading to exo-tetrahydroindolo[3,2-c] quinoline derivatives catalyzed by iodine

Article abstract of DOI:10.1002/ejoc.201200551

We report an iodine-catalyzed Povarov reaction using indole as dienophile carried out in toluene at room temperature. This three-component reaction, coupling an aldehyde, an amine, and an indole, proved to be an efficient method for synthesizing exo-indol

Full text of DOI:10.1002/ejoc.201200551

Job/Unit: O20551
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FULL PAPER
DOI: 10.1002/ejoc.201200551
A Stereoselective Povarov Reaction Leading to exo-Tetrahydroindolo-
[3,2-c]quinoline Derivatives Catalyzed by Iodine
Xiang-Shan Wang,*[a] Ming-Yue Yin,[a] Wei Wang,[a] and Shu-Jiang Tu[a]
Keywords: Multicomponent reactions / Homogeneous catalysis / Iodine / Diastereoselectivity / Heterocycles
We report an iodine-catalyzed Povarov reaction using indole
as dienophile carried out in toluene at room temperature.
This three-component reaction, coupling an aldehyde, an
amine, and an indole, proved to be an efficient method for
synthesizing exo-indolo[3,2-c]quinoline derivatives related
to the alkaloid isocryptolepine (cryptosanguinolentine) in
good yield and with high stereoselectivity.
Alder reaction, also called the Povarov reaction, provides,
in the presence of acid catalysts, easy access to quinoline
derivatives.[9–13] Imines derived from aromatic amines act as
heterodienes and undergo Povarov reactions with various
dienophiles. Generally, the electron-rich dienophiles are 2,3-
dihydrofurans, 3,4-dihydro-2H-pyrans, vinyl ethers, and en-
ols from aldehydes or ketones; seldom have indoles been
used.[14] However, the known reactions all give endo- and
exo-quinoline derivatives with poor stereoselectivity. There-
fore, the major task for the Povarov reaction is to improve
its stereoselectivity, and the one-pot synthesis of a single
exo-indoloquinoline is still a challenge.
Introduction
Cryptolepine (Figure 1, left) is one of a class of indol-
oquinoline alkaloids isolated from the roots of the West Af-
rican plant Cryptolepis sanguinolenta, which is an active
pharmaceutical ingredient in the roots used traditionally by
Ghanaian healers to treat a variety of health disorders in-
cluding clinical therapy of rheumatism, urinary-tract infec-
tions, malaria, and other diseases.[1] In addition, iso-crypto-
lepine (Figure 1, right), which is another major metabolite
out of 13 alkaloids isolated from this plant,[2] also shows
strong antiplasmodial activity.[3] Accordingly, novel strate-
gies for the synthesis of indoloquinolines continue to re-
ceive considerable attention in the field of synthetic organic
chemistry.[4,5]
Results and Discussion
Towards this goal, we tried to reduce the reaction tem-
perature of the Povarov reaction of 4-fluorobenzaldehyde,
3,4-(methylenedioxy)aniline, and indole in the presence of
various Lewis acids. Unfortunately, the desired product was
not formed at room temperature. Next, an amine with
higher reactivity, naphthalen-2-amine (2a) was selected in
order to promote the reaction, which has resulted in good
stereoselectivity in the past.[15] It first reacted with 4-fluoro-
benzaldehyde (1a) to produce a Schiff base, then indole was
introduced to the reaction mixture at room temperature in
the presence of iodine (5 mol-%) in toluene. Surprisingly,
the reaction proceeded smoothly, and the corresponding
exo-indolo[3,2-c]quinoline derivative (i.e., 4a) was obtained
in moderate yields and with high stereoselectivity
(Scheme 1). No other stereoisomers were detected based on
TLC and NMR spectroscopic analysis.
Figure 1. Cryptolepine and isocryptolepine.
Previously reported methods[6–8] for the synthesis of
indoloquinolines involve building an indole ring onto a
quinoline precursor. It is well known that the imino-Diels–
[a] School of Chemistry and Chemical Engineering, Jiangsu Key
Laboratory of Green Synthetic Chemistry for Functional
Materials, Xuzhou Normal University,
Subsequently, the reaction of 4-fluorobenzaldehyde (1a),
naphthalen-2-amine (2a) and indole (3a) was used as a
model reaction to optimize the experimental conditions.
The reaction was first carried out in toluene in the absence
of I2, and no reaction occurred under reflux conditions
(Table 1, Entry 1). However, when I2 (1, 5, or 10 mol-%)
Xuzhou Jiangsu 221116, P. R. China
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E-mail: xswang1974@yahoo.com
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Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201200551.
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X.-S. Wang, M.-Y. Yin, W. Wang, S.-J. Tu
FULL PAPER
aldehydes, including ethyl glyoxylate, butanal, heptanal, and
cyclohexanecarbaldehyde, all resulted in complex mixtures,
which were difficult to separate by column chromatography.
Substituted indoles, 5-bromoindole (3b) and 7-methylindole
(3c), were also chosen as dienophiles to react with 2a and
aldehydes, and they also gave satisfactory results (Table 2,
Entries 14–17). Aniline derivatives, for example, aniline, 3,4-
dimethoxyaniline, and 3,4-(methylenedioxy)aniline were se-
lected for this reaction, but the desired products were not
obtained. Therefore, only reactive amines, for instance,
naphthalen-2-amine (2a), 1H-indazol-5-amine (2b) and 9-
ethyl-9H-carbazol-3-amine (2c), could be included in this
reaction to give the products with high stereoselectivity. All
products were characterized by IR spectroscopy, 1H and
Scheme 1. Model reaction.
was added to the mixture, the reaction occurred, giving the
product in different yields, as shown in Table 1 (Entries 2–
4). A catalyst loading of 5 mol-% I2 at room temperature in
toluene gave the highest yield, while higher catalyst loading
resulted in no significant improvement in the yield. Other
Lewis acid catalysts, such as CuI, AlCl3, ZnCl2, AgOTf,
Yb(OTf)3, Fe(OTf)2, Bi(OTf)3, and Sc(OTf)3 (Table 1, En-
tries 9–16), were also tested in an attempt to further im-
prove the reaction, but none of them could produce a
higher yield than that obtained with iodine. In addition, the
effects of different solvents such as CH3CN, benzene, DMF,
and THF (Table 1, Entries 5–8) were compared; of these
solvents CH3CN was found to give the highest yield. How-
ever, in these cases, product 4a was formed in slightly lower
yields (Table 1, Entries 5–8) than with toluene.
Table 1. Synthetic results of 4a under different reaction condi-
tions.[a]
Entry
Catalyst
Amount
[mol-%]
Solvent
Yield[b]
[%]
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
–
I2
I2
I2
I2
I2
I2
I2
CuI
0
1
5
10
5
5
5
5
5
5
5
5
5
5
5
5
toluene
toluene
toluene
toluene
CH3CN
benzene
DMF
–
52
72
68
60
58
41
59
–
–
–
44
62
42
59
65
Scheme 2. Reaction of aldehyde, amine and indole.
THF
Table 2. Synthesis of 4 catalyzed by iodine.[a]
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
AlCl3
ZnCl2
AgOTf
Yb(OTf)3
Fe(OTf)2
Bi(OTf)3
Sc(OTf)3
Entry
Ar
2
3
4
Time Yield[b]
[h]
[%]
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
4-FC6H4
3-BrC6H4
3-O2NC6H4
2-ClC6H4
3-thienyl
4-MeC6H4
C6H5
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2b
2b
2b
2c
3a
3a
3a
3a
3a
3a
3a
3a
3a
3a
3a
3a
3a
3b
3b
3c
3c
3a
3a
3a
3a
4a
4b
4c
4d
4e
4f
4g
4h
4i
18
22
16
18
20
20
20
24
16
24
24
22
19
18
20
22
24
24
20
24
48
72
68
76
72
58
62
70
76
68
65
59
76
70
67
72
76
68
78
72
59
55
[a] Reagents and conditions: 4-fluorobenzaldehyde (1a; 0.124 g,
1.0 mmol), 2a (0.143 g, 1.0 mmol), 3a (0.117 g, 1.0 mmol), solvent
(10 mL). [b] Isolated yields.
piperonyl
4-O2NC6H4
3,5-(MeO)2C6H3
4-Me2NC6H4
4-MeOC6H4
3,4-Cl2C6H3
4-ClC6H4
4-CH3C6H4
4-ClC6H4
C6H5
Based on the optimized reaction conditions, we explored
variations in the structures of the aldehyde (i.e., 1), amine
(i.e., 2), and indole (i.e., 3) (Scheme 2 and Table 2).
Naphthalen-2-amine (2a) and indole (3a) were used as the
standard substrates initially. Entries 1–13 in Table 2 demon-
strate that the reaction also tolerates significant functionali-
zation of the aromatic aldehydes (i.e., 1); both electron-do-
nating groups (such as alkyl or alkoxy) and electron-with-
drawing groups (such as halo and nitro) can be accommo-
dated, and the aromatic ring may bear substituents in the
ortho, meta, or para positions. These aldehydes all reacted
well to provide a library of exo-indolo[3,2-c]quinoline deriv-
4j
4k
4l
4m
4n
4o
4p
4q
4r
4s
4t
4-ClC6H4
4-BrC6H4
4-FC6H4
4-BrC6H4
4u
[a] Reagents and conditions:
(1.0 mmol), I2 (0.05 mmol, 0.013 g), toluene (10 mL). [b] Isolated
1 (1.0 mmol), 2 (1.0 mmol), 3
atives 4a–m (Table 2). However, the reactions of aliphatic yields.
2
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A Stereoselective Povarov Reaction
13C NMR spectroscopy, and HRMS. The exo configura- was also confirmed by X-ray diffraction analysis, and its
tions of 4k and 4q were further confirmed by X-ray diffrac- crystal structure is shown in Figure 4.
tion analysis, and their crystal structures are shown in Fig-
ures 2 and 3, respectively.
According to literature precedent,[17] we believe that
iodine catalyzes the reaction as a mild Lewis acid. A tenta-
tively proposed mechanism is shown in Scheme 4. Schiff
base I may be formed first by the reaction of the aromatic
aldehyde and the amine, losing a molecule of H2O. Then
the Povarov reaction between iodine-activated Schiff base
II and the indole takes place stereoselectively to form inter-
mediate III, in which the larger aryl and indole groups are
on opposite faces of the quinoline ring, followed by tauto-
merization to give the final product (i.e., 4).
Figure 2. The crystal structure of product 4k.
Figure 4. The crystal structure of product 5a.
Figure 3. The crystal structure of product 4q.
An N-protected indole, N-methylindole (3d) was also
chosen as a dienophile to react with aldehyde 1 and
naphthalen-2-amine (2a), catalyzed by iodine in toluene at
room temperature. To our surprise, the above reaction gave
3-[(aryl)(1-methyl-1H-indol-3-yl)methyl]-1-methyl-1H-
indole derivatives 5a–c in high yields (based on the N-meth-
ylindole, Scheme 3). Furthermore, it gave the same results
when the corresponding Schiff base was used as reactant.
The structures of products 5 are in good agreement with
the structures of products of similar reactions reported in
the literature[16] by using aldehyde and N-methylindole as
starting materials and without amines. The structure of 5a Scheme 4. Possible reaction mechanism.
Scheme 3. Reaction of aldehyde and N-methylindole.
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X.-S. Wang, M.-Y. Yin, W. Wang, S.-J. Tu
FULL PAPER
Scheme 5. Reaction of Schiff base and indole.
(d, J = 8.8 Hz, 1 H), 7.74 (d, J = 8.0 Hz, 1 H), 7.93 (d, J = 8.4 Hz,
1 H) ppm. 13C NMR ([D6]DMSO, 100 MHz): δC = 45.4, 55.9, 56.4,
109.7, 110.3, 116.8, 118.3, 121.3, 121.4, 121.8, 125.0, 126.7, 127.2,
127.8, 128.0, 128.3, 129.0, 130.2, 130.6, 131.4, 133.7, 143.2, 144.1,
150.8 ppm. HRMS (ESI): calcd. for C25H20BrN2 [M + H]+
427.0810; found 427.0829.
The reaction of a preprepared Schiff base and indole 3a
was also carried out to verify the mechanism. It gave 4a in
81% yield (Scheme 5).
Conclusions
exo-8-(3-Nitrophenyl)-8,8a,13,13a-tetrahydro-7H-indolo[3,2-c]-
benzo[f]quinoline (4c): Yield 76 % (299 mg). Orange-yellow solid,
We have discovered a facile method to synthesize exo-
tetrahydroindolo[3,2-c]quinoline derivatives in a three-com-
ponent reaction between an aromatic aldehyde, a reactive
amine, and an indole, with iodine as catalyst. The advan-
tages of this method include mild reaction conditions, mod-
erate yields, high stereoselectivity, metal-free catalyst, and
operational simplicity.
m.p. 254–256 °C. IR (KBr): ν = 3389, 3365, 3045, 2834, 1625, 1613,
˜
1519, 1480, 1397, 1331, 1269, 1244, 1094, 1079, 920, 904, 819,
749 cm–1. 1H NMR ([D6]DMSO, 400 MHz): δH = 3.24 (dd, J =
10.0, J = 7.2 Hz, 1 H), 4.13 (d, J = 10.4 Hz, 1 H), 5.17 (dd, J =
6.4, J = 4.0 Hz, 1 H), 6.02 (d, J = 7.6 Hz, 1 H), 6.36–6.40 (m, 1
H), 6.44 (d, J = 2.8 Hz, 1 H), 6.71 (d, J = 8.0 Hz, 1 H), 6.77 (s, 1
H), 6.99 (t, J = 7.6 Hz, 1 H), 7.09 (d, J = 8.8 Hz, 1 H), 7.23–7.27
(m, 1 H), 7.48 (t, J = 7.6 Hz, 1 H), 7.66–7.77 (m, 4 H), 7.95 (d, J
= 8.4 Hz, 1 H), 8.17 (s, 1 H), 8.27 (d, J = 8.0 Hz, 1 H) ppm. 13C
NMR ([D6]DMSO, 100 MHz): δC = 45.6, 55.7, 56.4, 109.8, 110.5,
116.8, 118.3, 121.5, 121.9, 122.8, 123.3, 125.0, 126.7, 127.3, 127.9,
128.3, 128.4, 128.7, 129.6, 133.6, 135.8, 143.1, 143.8, 147.5,
150.8 ppm. HRMS (ESI): calcd. for C25H20N3O2 [M + H]+
394.1556; found 394.1565.
Experimental Section
General Procedure for the Synthesis of Indolo[3,2-c]quinoline Deriva-
tives 4: Aromatic aldehyde (1.0 mmol), amine (1.0 mmol), and tolu-
ene (10 mL) were added to a 50 mL flask, and the mixture was
stirred at room temperature for 30 min. Then, indole (1.0 mmol)
and I2 (0.013 g, 0.05 mmol) were added to the mixture, which was
stirred at room temperature for another 16–48 h until it reached
completion. Reaction progress was monitored by TLC. Products 4
were purified by column chromatography using ethyl acetate/petro-
leum ether (1:5) as eluent.
exo-8-(2-Chlorophenyl)-8,8a,13,13a-tetrahydro-7H-indolo[3,2-c]-
benzo[f]quinoline (4d): Yield 72% (276 mg). Pale green solid, m.p.
229–230 °C. IR (KBr): ν = 3343, 3170, 3057, 1625, 1561, 1524,
˜
1490, 1467, 1439, 1400, 1355, 1337, 1273, 1247, 1226, 1100, 1056,
1
1037, 917, 814, 744 cm–1. H NMR ([D6]DMSO, 400 MHz): δH
=
exo-8-(4-Fluorophenyl)-8,8a,13,13a-tetrahydro-7H-indolo[3,2-c]-
benzo[f]quinoline (4a): Yield 72% (264 mg). Pink solid, m.p. 214–
3.26 (dd, J = 10.4, J = 6.8 Hz, 1 H), 4.61 (d, J = 10.4 Hz, 1 H),
5.15 (dd, J = 6.4, J = 3.6 Hz, 1 H), 6.05 (d, J = 7.2 Hz, 1 H), 6.36–
6.40 (m, 2 H), 6.61 (s, 1 H), 6.67 (d, J = 8.0 Hz, 1 H), 6.94–6.98
(m, 1 H), 7.08 (d, J = 8.8 Hz, 1 H), 7.22–7.25 (m, 1 H), 7.38–7.39
(m, 2 H), 7.45–7.52 (m, 2 H), 7.64 (d, J = 8.8 Hz, 1 H), 7.74 (d, J
= 8.0 Hz, 1 H), 7.81 (d, J = 7.0 Hz, 1 H), 7.94 (d, J = 8.4 Hz, 1 H)
ppm. 13C NMR (CDCl3, 100 MHz): δC = 46.7, 52.4, 56.9, 110.1,
118.2, 119.1, 121.3, 121.8, 122.3, 125.1, 127.2, 127.3, 128.3, 128.4,
129.0, 129.2, 129.3, 129.4, 129.5, 131.7, 133.9, 135.1, 138.5, 142.8,
149.8 ppm. HRMS (ESI): calcd. for C25H19ClN2Na [M + Na]+
405.1134; found 405.1148.
216 °C. IR (KBr): ν = 3401, 3376, 3039, 2843, 1667, 1628, 1604,
˜
1522, 1506, 1482, 1405, 1337, 1308, 1274, 1247, 1209, 1192, 1155,
1
1093, 1014, 831, 813, 743 cm–1. H NMR ([D6]DMSO, 400 MHz):
δH = = 3.18 (dd, J = 10.4, J = 7.2 Hz, 1 H), 3.94 (d, J = 10.4 Hz,
1 H), 5.14 (dd, J = 7.2, J = 3.2 Hz, 1 H), 6.02 (d, J = 7.2 Hz, 1
H), 6.36–6.41 (m, 2 H), 6.60 (s, 1 H), 6.68 (d, J = 8.0 Hz, 1 H),
6.96 (t, J = 7.6 Hz, 1 H), 7.09 (d, J = 8.8 Hz, 1 H), 7.20–7.22 (m,
3 H), 7.34–7.37 (m, 2 H), 7.44–7.48 (m, 1 H), 7.63 (d, J = 8.8 Hz,
1 H), 7.73 (d, J = 8.0 Hz, 1 H), 7.93 (d, J = 8.4 Hz, 1 H) ppm. 13C
NMR ([D6]DMSO, 100 MHz): δC = 45.6, 55.6, 56.5, 109.6, 110.2,
114.6, 114.8, 116.8, 118.3, 121.3, 121.9, 125.0, 126.6, 127.1, 127.7,
128.2, 128.3, 129.2, 130.7, 130.8, 133.8, 137.6, 143.4, 150.8 ppm.
HRMS (ESI): calcd. for C25H20FN2 [M + H]+ 367.1611; found
367.1611.
exo-8-(2-Thienyl)-8,8a,13,13a-tetrahydro-7H-indolo[3,2-c]benzo[f]-
quinoline (4e): Yield 58% (205 mg). Silver-white solid, m.p. 232–
233 °C. IR (KBr): ν = 3366, 3090, 3054, 3032, 2842, 1622, 1519,
˜
1484, 1398, 1297, 1270, 1249, 1095, 918, 818, 757, 749, 717 cm–1.
1H NMR (CDCl3, 400 MHz): δH = 3.34 (dd, J = 10.4, J = 6.8 Hz,
1 H), 4.49 (d, J = 10.4 Hz, 1 H), 4.54 (s, 1 H), 4.73 (s, 1 H), 5.38
exo-8-(3-Bromophenyl)-8,8a,13,13a-tetrahydro-7H-indolo[3,2-c]-
benzo[f]quinoline (4b): Yield 68% (290 mg). Cream solid, m.p. 184–
186 °C. IR (KBr): ν = 3373, 3043, 2840, 1667, 1624, 1569, 1518, (d, J = 6.8 Hz, 1 H), 6.45 (d, J = 7.2 Hz, 1 H), 6.62 (t, J = 7.2 Hz,
˜
1479, 1427, 1397, 1334, 1294, 1269, 1242, 1085, 1070, 887, 816,
1 H), 6.75 (d, J = 8.0 Hz, 1 H), 6.85 (d, J = 2.8 Hz, 1 H), 6.91 (d,
J = 8.8 Hz, 1 H), 6.98–7.00 (m, 1 H), 7.09–7.12 (m, 1 H), 7.28–
7.31 (m, 1 H), 7.36 (d, J = 5.2 Hz, 1 H),7.50–7.54 (m, 1 H), 7.65
(d, J = 8.8 Hz, 1 H), 7.76 (d, J = 8.0 Hz, 1 H), 7.86 (d, J = 8.4 Hz,
1
784, 751 cm–1. H NMR ([D6]DMSO, 400 MHz): δH = 3.21 (dd, J
= 10.4, J = 6.8 Hz, 1 H), 3.93 (d, J = 10.4 Hz, 1 H), 5.13 (dd, J =
6.8 Hz, 1 H), 6.05 (d, J = 7.2 Hz, 1 H), 6.39–6.42 (m, 2 H), 6.67–
6.70 (m, 2 H), 6.96–6.99 (m, 1 H), 7.08 (d, J = 8.8 Hz, 1 H), 7.21– 1 H) ppm. 13C NMR ([D6]DMSO, 100 MHz): δC = 47.5, 52.0, 56.4,
7.25 (m, 1 H), 7.29 (d, J = 8.0 Hz, 1 H), 7.34–7.38 (m, 1 H), 7.47 109.6, 110.6, 116.9, 118.3, 121.5, 122.0, 125.0, 125.4, 126.2, 126.6,
(d, J = 7.2 Hz, 1 H), 7.52 (s, 1 H), 7.58 (d, J = 8.0 Hz, 1 H), 7.64
127.3, 127.8, 128.26, 128.29, 129.2, 133.6, 142.9, 145.1, 150.7 ppm.
4
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A Stereoselective Povarov Reaction
HRMS (ESI): calcd. for C23H19N2S [M + H]+ 355.1269; found
355.1275.
127.9, 128.3, 128.4, 128.7, 130.2, 133.7, 143.0, 147.1, 149.4,
150.8 ppm. HRMS (ESI): calcd. for C25H20N3O2 [M + H]+
394.1556; found 394.1527.
exo-8-(4-Methylphenyl)-8,8a,13,13a-tetrahydro-7H-indolo[3,2-c]-
benzo[f]quinoline (4f): Yield 62% (225 mg). Cream-colored solid,
exo-8-(3,5-Dimethoxyphenyl)-8,8a,13,13a-tetrahydro-7H-indolo-
[3,2-c]benzo[f]quinoline (4j): Yield 65% (266 mg). Pink solid, m.p.
m.p. 197–198 °C. IR (KBr): ν = 3388, 3355, 3055, 2927, 2822, 1660,
˜
1624, 1608, 1516, 1478, 1461, 1398, 1328, 1266, 1242, 1179, 1091,
213-214 °C. IR (KBr): ν = 3356, 3056, 3030, 3007, 2940, 2835,
˜
1
1018, 811, 752, 739 cm–1. H NMR (CDCl3, 400 MHz): δH = 2.41
1626, 1606, 1519, 1471, 1428, 1402, 1344, 1290, 1245, 1203, 1150,
1
(s, 3 H), 3.31 (dd, J = 10.4, J = 7.2 Hz, 1 H), 4.12 (d, J = 10.4 Hz,
1 H), 4,36 (s, 1 H), 4.71 (s, 1 H),5.36 (dd, J = 6.8 Hz, 1 H), 6.24
(d, J = 7.6 Hz, 1 H), 6.53–6.57 (m, 1 H), 6.75 (d, J = 7.6 Hz, 1 H),
1062, 995, 927, 826, 817, 745 cm–1. H NMR (CDCl3, 400 MHz):
δH = 3.29 (dd, J = 10.4, J = 7.2 Hz, 1 H), 3.77 (s, 6 H), 4.09 (d, J
= 10.4 Hz, 1 H), 4.40 (s, 1 H), 4.73 (s, 1 H), 5.36 (d, J = 6.8 Hz, 1
6.88 (t, J = 8.8 Hz, 1 H), 7.07 (t, J = 7.6 Hz, 1 H), 7.17–7.22 (m, H), 6.38 (d, J = 6.8 Hz, 1 H), 6.48 (s, 3 H), 6.57–6.61 (m, 1 H),
4 H), 7.29 (d, J = 7.6 Hz, 1 H), 7.49–7.53 (m, 1 H), 7.64 (d, J = 6.75 (d, J = 8.0 Hz, 1 H), 6.90 (d, J = 8.8 Hz, 1 H), 7.08 (t, J =
8.8 Hz, 1 H), 7.75 (d, J = 8.0 Hz, 1 H), 7.86 (d, J = 8.0 Hz, 1 H)
ppm. 13C NMR (CDCl3, 100 MHz): δC = 21.3, 46.8, 56.9, 57.0,
110.0, 111.2, 113.2, 118.1, 118.5, 121.2, 122.1, 126.2, 127.3, 128.2,
7.6 Hz, 1 H), 7.27–7.30 (m, 1 H), 7.49–7.53 (m, 1 H), 7.65 (d, J =
8.8 Hz, 1 H), 7.75 (d, J = 8.0 Hz, 1 H), 7.86 (d, J = 8.4 Hz, 1 H)
ppm. 13C NMR ([D6]DMSO, 100 MHz): δC = 46.8, 55.4, 57.0, 57.5,
128.3, 128.6, 129.0, 129.1, 129.2, 129.9, 134.0, 137.8, 138.0, 100.4, 106.5, 110.1, 111.1, 118.1, 118.6, 118.7, 121.2, 122.2, 126.5,
142.8 ppm. HRMS (ESI): calcd. for C26H23N2 [M + H]+ 363.1861;
found 363.1843.
127.3, 128.3, 129.0, 129.3, 129.7, 133.9, 142.6, 143.5, 160.7 ppm.
HRMS (ESI): calcd. for C27H25N2O2 [M + H]+ 409.1916; found
409.1919.
exo-8-Phenyl-8,8a,13,13a-tetrahydro-7H-indolo[3,2-c]benzo[f]quino-
line (4g): Yield 70% (244 mg). Pale yellow solid, m.p. 197–199 °C.
exo-8-[4-(Dimethylamino)phenyl]-8,8a,13,13a-tetrahydro-7H-
indolo[3,2-c]benzo[f]quinoline (4k): Yield 59% (231 mg). Green so-
IR (KBr): ν = 3369, 3051, 3029, 2950, 2848, 1623, 1518, 1428, 1397,
˜
1
1330, 1298, 1271, 1241, 1096, 1077, 813, 750, 706 cm–1. H NMR
lid, m.p. 224–225 °C. IR (KBr): ν = 3354, 3038, 2930, 2817, 1625,
˜
([D6]DMSO, 400 MHz): δH = 3.20 (dd, J = 10.4, J = 7.2 Hz, 1 H),
1610, 1520, 1479, 1460, 1441, 1401, 1359, 1329, 1267, 1240, 1185,
1
3.93 (d, J = 10.4 Hz, 1 H), 5.14 (dd, J = 7.2, J = 3.6 Hz, 1 H), 5.98 1164, 1089, 811, 756, 744 cm–1. H NMR ([D6]DMSO, 400 MHz):
(d, J = 7.2 Hz, 1 H), 6.34–6.38 (m, 2 H), 6.60 (s, 1 H), 6.69 (d, J
= 7.6 Hz, 1 H), 6.95 (t, J = 7.6 Hz, 1 H), 7.11 (d, J = 8.8 Hz, 1 H),
7.21–7.24 (m, 1 H), 7.31–7.33 (m, 2 H), 7.38–7.42 (m, 3 H), 7.45–
7.48 (m, 1 H), 7.63 (d, J = 8.8 Hz, 1 H), 7.73 (d, J = 8.0 Hz, 1 H),
7.94 (d, J = 8.4 Hz, 1 H) ppm. 13C NMR ([D6]DMSO, 100 MHz):
δC = 45.6, 56.3, 56.5, 109.6, 110.1, 116.7, 118.4, 121.2, 121.8, 125.0,
126.6, 127.1, 127.6, 127.7, 128.0, 128.2, 128.3, 128.9, 129.4,133.8,
141.3, 143.4, 150.7 ppm. HRMS (ESI): calcd. for C25H21N2 [M +
H]+ 349.1705; found 349.1709.
δH = 2.92 (s, 6 H), 3.16 (dd, J = 10.0, J = 4.8 Hz, 1 H), 3.81 (d, J
= 10.4 Hz, 1 H), 5.11–5.12 (m, 1 H), 6.09 (d, J = 7.6 Hz, 1 H), 6.31
(s, 1 H), 6.36–6.39 (m, 1 H), 6.42 (s, 1 H), 6.66 (d, J = 8.0 Hz, 1
H), 6.74 (d, J = 8.4 Hz, 2 H), 6.94 (t, J = 7.6 Hz, 1 H), 7.08–7.14
(m, 3 H), 7.19–7.22 (m, 1 H), 7.43–7.47 (m, 1 H), 7.60 (d, J =
8.8 Hz, 1 H), 7.71 (d, J = 8.0 Hz, 1 H), 7.92 (d, J = 8.4 Hz, 1 H)
ppm. 13C NMR ([D6]DMSO, 100 MHz): δC = 40.2, 45.4, 55.6, 56.5,
109.5, 110.0, 111.9, 116.8, 118.4, 121.1, 121.8, 125.2, 126.6, 127.0,
127.4, 128.1, 128.3, 128.6, 129.3, 129.9, 133.8, 143.6, 150.1,
150.7 ppm. HRMS (ESI): calcd. for C27H26N3 [M + H]+ 392.2127;
found 392.2134.
exo-8-Piperonyl-8,8a,13,13a-tetrahydro-7H-indolo[3,2-c]benzo[f]-
quinoline (4h): Yield 76% (298 mg). Pink solid, m.p. 209–211 °C.
IR (KBr): ν = 3401, 3372, 3036, 2892, 2829, 2781, 1625, 1607, 1517,
exo-8-(4-Methoxyhenyl)-8,8a,13,13a-tetrahydro-7H-indolo[3,2-c]-
benzo[f]quinoline (4l): Yield 76 % (288 mg). Cream-colored solid,
˜
1496, 1481, 1440, 1398, 1378, 1330, 1267, 1244, 1205, 1185, 1098,
1035, 928, 886, 822, 806, 745 cm–1
.
1H NMR ([D6]DMSO,
m.p. 226–228 °C. IR (KBr): ν = 3402, 3353, 3030, 3003, 2932, 2834,
˜
400 MHz): δH = 3.18 (dd, J = 10.0, J = 7.2 Hz, 1 H), 3.86 (d, J =
10.4 Hz, 1 H), 5.12–5.13 (m, 1 H), 6.07 (d, J = 4.0 Hz, 2 H), 6.15
(d, J = 7.2 Hz, 1 H), 6.35 (s, 1 H), 6.42 (d, J = 7.2 Hz, 1 H), 6.53
(s, 1 H), 6.68 (d, J = 7.6 Hz, 2 H), 6.89 (d, J = 8.0 Hz, 1 H), 6.94–
1624, 1608, 1510, 1479, 1464, 1400, 1299, 1267, 1246, 1173, 1112,
1092, 1033, 826, 820, 755, 746 cm–1 1H NMR ([D6]DMSO,
.
400 MHz): δH = 3.16 (dd, J = 10.4, J = 7.2 Hz, 1 H), 3.79 (s, 3 H),
3.87 (d, J = 10.4 Hz, 1 H), 5.12 (d, J = 7.2 Hz, 1 H), 6.03 (d, J =
7.00 (m, 2 H), 7.09 (dd, J = 8.8, J = 1.6 Hz, 1 H), 7.20–7.24 (m, 1 7.2 Hz, 1 H), 6.36–6.39 (m, 2 H), 6.51 (s, 1 H), 6.67 (d, J = 8.0 Hz,
H), 7.44–7.48 (m, 1 H), 7.62 (d, J = 8.8 Hz, 1 H), 7.73 (d, J = 1 H), 6.94–6.96 (m, 3 H), 7.09 (d, J = 8.8 Hz, 1 H), 7.22–7.24 (m,
8.0 Hz, 1 H), 7.93 (d, J = 8.4 Hz, 1 H) ppm. 13C NMR (CDCl3,
100 MHz): δC = 46.8, 57.0, 77.24, 101.1, 107.9, 108.5, 110.1, 111.1,
3 H), 7.44–7.47 (m, 1 H), 7.61 (d, J = 8.8 Hz, 1 H), 7.71 (d, J =
7.6 Hz, 1 H), 7.92 (d, J = 8.4 Hz, 1 H) ppm. 13C NMR ([D6]-
118.1, 118.7, 121.2, 122.2, 122.5, 126.2, 127.3, 128.26, 128.30, DMSO, 100 MHz): δC = 45.6, 55.1, 55.6, 56.5, 109.5, 110.1, 113.4,
129.0, 129.3, 129.9, 133.9, 134.9, 142.7, 147.4, 147.8 ppm. HRMS
116.8, 118.4, 121.2, 121.8, 125.1, 126.6, 127.1, 127.6, 128.2, 128.3,
129.6, 129.9, 133.3, 133.8, 143.5, 150.7, 158.8 ppm. HRMS (ESI):
calcd. for C26H22N2ONa [M + Na]+ 401.1630; found 401.1632.
(ESI): calcd. for C26H21N2O2 [M + H]+ 393.1603; found 393.1600.
exo-8-(4-Nitrophenyl)-8,8a,13,13a-tetrahydro-7H-indolo[3,2-c]-
benzo[f]quinoline (4i): Yield 68% (267 mg). Yellow solid, m.p. 228– exo-8-(3,4-Dichlorophenyl)-8,8a,13,13a-tetrahydro-7H-indolo[3,2-c]-
230 °C. IR (KBr): ν = 3401, 3382, 3055, 3039, 2830, 1624, 1609, benzo[f]quinoline (4m): Yield 70% (292 mg). Pink solid, m.p. 231–
˜
1597, 1516, 1480, 1466, 1393, 1345, 1325, 1291, 1266, 1249, 1238,
1147, 1110, 1090, 1062, 1016, 852, 821, 752, 700 cm–1. 1H NMR
(CDCl3, 400 MHz): δH = 3.29 (dd, J = 10.4, J HzЈ = 6.8 Hz, 1 H),
233 °C. IR (KBr): ν = 3396, 3368, 3053, 3031, 2926, 2850, 1624,
˜
1611, 1560, 1520, 1475, 1463, 1396, 1328, 1269, 1241, 1186, 1149,
1093, 1064, 1049, 877, 814, 780, 753, 741 cm–1. 1H NMR ([D6]
4.32 (d, J = 10.4 Hz, 1 H), 4.39 (s, 1 H), 4.78 (s, 1 H), 5.39 (d, J = DMSO, 400 MHz): δH = 3.24 (dd, J = 10.0, J = 7.2 Hz, 1 H), 4.57
7.2 Hz, 1 H), 6.15–6.17 (m, 1 H), 6.55–6.58 (m, 1 H), 6.77 (d, J = (d, J = 10.4 Hz, 1 H), 5.14 (d, J = 6.0 Hz, 1 H), 6.12 (d, J = 7.6 Hz,
7.6 Hz, 1 H), 6.94 (d, J = 8.8 Hz, 1 H), 7.09–7.13 (m, 1 H), 7.30–
1 H), 6.41–6.44 (m, 2 H), 6.63 (s, 1 H), 6.68 (d, J = 7.6 Hz, 1 H),
7.34 (m, 1 H), 7.50–7.56 (m, 3 H), 7.69 (d, J = 8.8 Hz, 1 H), 7.78 6.97 (t, J = 7.6 Hz, 1 H), 7.06 (d, J = 8.8 Hz, 1 H), 7.24 (t, J =
(d, J = 8.0 Hz, 1 H), 7.87 (d, J = 8.4 Hz, 1 H), 8.25 (d, J = 8.8 Hz,
2 H). 13C NMR ([D6]DMSO, 100 MHz): δC = 45.6, 55.9, 56.4,
109.8, 110.4, 116.9, 118.3, 121.5, 121.9, 123.1, 124.9, 126.7, 127.3,
7.2 Hz, 1 H), 7.46–7.49 (m, 1 H), 7.56–7.60 (m, 2 H), 7.65 (d, J =
8.8 Hz, 1 H), 7.75 (d, J = 8.0 Hz, 1 H), 8.83 (d, J = 8.4 Hz, 1 H),
7.94 (d, J = 8.8 Hz, 1 H) ppm. 13C NMR ([D6]DMSO, 100 MHz):
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5

Job/Unit: O20551
/KAP1
Date: 18-07-12 17:48:54
Pages: 9
X.-S. Wang, M.-Y. Yin, W. Wang, S.-J. Tu
FULL PAPER
δC = 45.3, 51.0, 56.5, 109.6, 110.4, 117.3, 118.3, 119.8, 121.5, 121.9,
124.1, 126.7, 127.2, 127.7, 127.8, 128.2, 128.3, 128.5, 131.6, 132.6,
133.7, 135.0, 137.9, 143.3, 150.9 ppm. HRMS (ESI): calcd. for
C25H19Cl2N2 [M + H]+ 417.0925; found 417.0912.
HRMS (ESI): calcd. for C26H22N2 [M – H]+ 361.1703; found
361.1730.
exo-7-(4-Chlorophenyl)-3,6,7,7a,12,12a-hexahydroindolo[3,2-c]pyr-
azolo[4,3-f]quinoline (4r): Yield 78% (291 mg). White solid, m.p.
exo-10-Bromo-8-(4-chlorophenyl)-8,8a,13,13a-tetrahydro-13H-benzo-
[f]indolo[3,2-c]quinoline (4n): Yield 67% (309 mg). Pale yellow solid,
262–264 °C. IR (KBr): ν = 3343, 3279, 3178, 3050, 2969, 2845,
˜
1629, 1609, 1483, 1439, 1344, 1329, 1273, 1245, 1162, 1090, 1080,
1046, 1016, 941, 885, 835, 795, 753 cm–1. 1H NMR ([D6]DMSO,
400 MHz): δH = 3.26–3.31 (m, 1 H), 3.79 (d, J = 10.4 Hz, 1 H),
4.97 (dd, J = 7.6, J = 4.0 Hz, 1 H), 5.95 (d, J = 7.2 Hz, 1 H), 5.99
(s, 1 H), 6.36 (d, J = 7.8 Hz, 1 H), 6.39 (s, 1 H), 6.64 (d, J = 8.0 Hz,
1 H), 6.91–6.97 (m, 2 H), 7.28 (d, J = 8.4 Hz, 1 H), 7.35 (d, J =
8.4 Hz, 2 H), 7.45 (d, J = 8.4 Hz, 2 H), 8.18 (s, 1 H), 12.78 (s, 1
H) ppm. 13C NMR ([D6]DMSO, 100 MHz): δC = 46.5, 56.0, 57.0,
109.4, 109.7, 112.7, 116.8, 117.9, 123.3, 125.2, 127.7, 127.9, 128.8,
130.7, 131.3, 132.0, 134.9, 139.1, 140.7, 151.2 ppm. HRMS (ESI):
calcd. for C22H17ClN4Na [M + Na]+ 395.1039; found 395.1085.
m.p. 235–238 °C. IR (KBr): ν = 3370, 3061, 2932, 2844, 1625, 1604,
˜
1520, 1476, 1427, 1407, 1336, 1308, 1300, 1281, 1250, 1187, 1104,
1094, 1066, 1015, 876, 810, 747 cm–1 1H NMR ([D6]DMSO,
.
400 MHz): δH = 3.21 (dd, J = 10.0, J = 7.2 Hz, 1 H), 3.94 (d, J =
10.0 Hz, 1 H), 5.17 (d, J = 7.2 Hz, 1 H), 6.07 (d, J = 1.6 Hz, 1 H),
6.61–6.66 (m, 3 H), 7.07 (d, J = 8.8 Hz, 1 H), 7.11 (dd, J = 8.4, J
= 7.0 Hz, 1 H), 7.20–7.24 (m, 1 H), 7.33 (d, J = 8.4 Hz, 2 H), 7.45–
7.49 (m, 3 H), 7.64 (d, J = 8.4 Hz, 1 H), 7.74 (d, J = 8.0 Hz, 1 H),
7.88 (d, J = 8.4 Hz, 1 H) ppm. 13C NMR ([D6]DMSO, 100 MHz):
δC = 45.5, 55.4, 56.6, 107.2, 109.7, 111.1, 118.3, 121.5, 121.7, 126.7,
127.2, 127.6, 128.0, 128.35, 128.44, 130.2, 130.7, 131.8, 132.3,
133.6, 140.0, 143.4, 150.1 ppm. HRMS (ESI): calcd. for
C25H19BrClN2 [M + H]+ 461.0420; found 461.0395.
exo-7-(4-Bromophenyl)-3,6,7,7a,12,12a-hexahydroindolo[3,2-c]pyr-
azolo[4,3-f]quinoline (4s): Yield 72% (301 mg). Cream-colored so-
lid, m.p. 184–186 °C. IR (KBr): ν = 3373, 3043, 2840, 1667, 1624,
˜
exo-10-Bromo-8-(p-tolyl)-8,8a,13,13a-tetrahydro-13H-benzo[f]ind-
olo[3,2-c]quinoline (4o): Yield 72% (317 mg). White solid, m.p. 236–
1569, 1518, 1479, 1427, 1397, 1334, 1294, 1269, 1242, 1085, 1070,
887, 816, 784, 751 cm–1. 1H NMR ([D6]DMSO, 400 MHz): δH
=
238 °C. IR (KBr): ν = 3373, 3058, 3029, 2914, 2846, 1625, 1605,
˜
3.26–3.31 (m, 1 H), 3.78 (d, J = 10.8 Hz, 1 H), 4.97 (d, J = 4.4 Hz,
1 H), 5.96 (d, J = 7.2 Hz, 1 H), 5.99 (s, 1 H), 6.37 (d, J = 7.6 Hz,
1 H), 6.40 (s, 1 H), 6.64 (d, J = 7.6 Hz, 1 H), 6.91–6.97 (m, 2 H),
7.28 (d, J = 8.0 Hz, 3 H), 7.58 (d, J = 8.0 Hz, 2 H), 8.18 (s, 1 H),
12.79 (s, 1 H) ppm. 13C NMR ([D6]DMSO, 100 MHz): δC = 46.4,
56.0, 57.0, 109.4, 109.8, 116.8, 117.0, 120.5, 124.0, 125.2, 127.7,
128.8, 130.8, 131.1, 131.2, 134.8, 138.6, 139.1, 141.1, 151.2 ppm.
HRMS (ESI): calcd. for C22H17BrN4Na [M + Na]+ 439.0543;
found 439.0573.
1519, 1476, 1427, 1406, 1338, 1302, 1251, 1104, 1092, 877, 817,
807, 746 cm–1. 1H NMR (CDCl3, 400 MHz): δH = 2.42 (s, 3 H),
3.26 (dd, J = 10.4, J = 7.2, 1 H), 4.08 (d, J = 10.4 Hz, 1 H), 4.37
(s, 1 H), 4.73 (s, 1 H), 5.36 (d, J = 7.2 Hz, 1 H), 6.28 (d, J = 1.6 Hz,
1 H), 6.60 (d, J = 8.0 Hz, 1 H), 6.87 (d, J = 8.8 Hz, 1 H), 7.15–
7.20 (m, 5 H), 7.28–7.30 (m, 1 H), 7.49–7.53 (m, 1 H), 7.64 (d, J
= 8.4 Hz, 1 H), 7.75 (d, J = 8.0 Hz, 1 H), 7.83 (d, J = 8.4 Hz, 1 H)
ppm. 13C NMR ([D6]DMSO, 100 MHz): δC = 20.8, 45.5, 55.7, 56.3,
107.1, 109.5, 110.9, 113.8, 118.4, 121.3, 121.7, 126.6, 127.1, 127.7,
128.3, 128.6, 128.7, 130.0, 132.2, 133.7, 137.0, 137.9, 143.4,
150.1 ppm. HRMS (ESI): calcd. for C26H22BrN2 [M + H]+
441.0966; found 441.0943.
exo-7-(4-Fluorophenyl)-3,6,7,7a,12,12a-hexahydroindolo[3,2-c]pyr-
azolo[4,3-f]quinoline (4t): Yield 59 % (210 mg). White solid, m.p.
254–256 °C. IR (KBr): ν = 3308, 3284, 3108, 3032, 2925, 2874,
˜
1628, 1608, 1591, 1536, 1507, 1434, 1388, 1356, 1325, 1258, 1220,
1156, 1106, 1093, 1004, 950, 846, 820, 808, 746 cm–1. 1H NMR
([D6]DMSO, 400 MHz): δH = 3.26–3.31 (m, 1 H), 3.80 (d, J =
10.4 Hz, 1 H), 4.96 (s, 1 H), 5.93 (s, 1 H), 5.94 (d, J = 6.4 Hz, 1
H), 6.36 (s, 2 H), 6.64 (d, J = 7.6 Hz, 1 H), 6.93–6.96 (m, 2 H),
7.21 (t, J = 8.4 Hz, 2 H), 7.28 (d, J = 8.4 Hz, 1 H), 7.34–7.37 (m,
2 H), 8.18 (s, 1 H), 12.77 (s, 1 H) ppm. 13C NMR ([D6]DMSO,
100 MHz): δC = 46.7, 56.0, 57.0, 109.37, 109.40, 109.7, 114.5, 114.8,
116.8, 123.3, 125.2, 127.7, 129.0, 130.7, 130.8, 131.3, 134.9, 137.89,
137.92, 139.2, 151.2, 160.4 ppm. HRMS (ESI): calcd. for
C22H17FN4Na [M + Na]+ 379.1335; found 379.1325.
exo-8-(4-Chlorophenyl)-12-methyl-8,8a,13,13a-tetrahydro-13H-
benzo[f]indolo[3,2-c]quinoline (4p): Yield 76% (302 mg). Pale yellow
solid, m.p. 229–231 °C. IR (KBr): ν = 3392, 3346, 3046, 2931, 2845,
˜
1627, 1604, 1519, 1489, 1404, 1332, 1311, 1271, 1239, 1095, 922,
1
856, 812, 770, 751, 734 cm–1. H NMR (CDCl3, 400 MHz): δH
=
2.19 (s, 3 H), 3.28 (dd, J = 10.4, J = 7.2 Hz, 1 H), 4.15 (d, J =
10.4 Hz, 1 H), 4.35 (s, 1 H), 4.54 (s, 1 H), 5.36 (d, J = 7.2 Hz, 1
H), 6.10 (d, J = 7.2 Hz, 1 H), 6.50–6.54 (m, 1 H), 6.90 (d, J =
8.4 Hz, 1 H), 6.93 (d, J = 7.6 Hz, 1 H), 7.24–7.36 (m, 5 H), 7.51–
7.55 (m, 1 H), 7.65 (d, J = 8.8 Hz, 1 H), 7.74 (d, J = 8.0 Hz, 1 H),
7.88 (d, J = 8.8 Hz, 1 H) ppm. 13C NMR ([D6]DMSO, 100 MHz):
δC = 20.8, 45.5, 55.7, 56.6, 107.1, 109.5, 111.0, 113.7, 118.4, 121.3,
121.7, 126.6, 127.1, 127.7, 128.3, 128.6, 128.7, 130.0, 132.2, 133.7,
137.0, 137.9, 143.4, 150.1 ppm. HRMS (ESI): calcd. for
C26H20ClN2 [M – H]+ 395.1314; found 395.1278.
exo-9-(4-Bromophenyl)-5-ethyl-5,8,9,9a,14,14a-hexahydroindolo-
[2Ј,3Ј:4,5]pyrido[2,3-c]carbazole (4u): Yield 55% (272 mg). Pale yel-
low solid, m.p. 255–257 °C. IR (KBr): ν = 3340, 3263, 3051, 2974,
˜
2932, 2824, 1609, 1590, 1505, 1472, 1456, 1403, 1383, 1328, 1260,
1185, 1152, 1091, 1069, 1011, 830, 796, 752, 739 cm–1. 1H NMR
([D6]DMSO, 400 MHz): δH = 1.28 (t, J = 6.8 Hz, 3 H), 3.25 (dd, J
exo-12-Methyl-8-phenyl-8,8a,13,13a-tetrahydro-13H-benzo[f]ind-
olo[3,2-c]quinoline (4q): Yield 68% (246 mg). Pink solid, m.p. 206–
208 °C. IR (KBr): ν = 3394, 3362, 3035, 2975, 2925, 2828, 1621, = 9.6, J = 7.2 Hz, 1 H), 3.94 (d, J = 10.0 Hz, 1 H), 4.42 (q, J =
˜
1605, 1518, 1466, 1394, 1357, 1332, 1267, 1238, 1178, 1162, 1094,
1069, 1030, 992, 853, 809, 774, 760, 744 cm–1 1H NMR ([D6]
DMSO, 400 MHz): δH = 2.16 (s, 3 H), 3.20–3.24 (m, 1 H), 3.89 (d,
6.8 Hz, 2 H), 5.39 (d, J = 5.6 Hz, 1 H), 6.02 (s, 1 H), 6.03 (s, 1 H),
6.12 (d, J = 7.2 Hz, 1 H), 6.40–6.43 (m, 1 H), 6.74 (d, J = 7.6 Hz,
1 H), 6.96 (t, J = 7.6 Hz, 1 H), 7.01 (d, J = 8.8 Hz, 1 H), 7.15–7.19
.
J = 10.4 Hz, 1 H), 5.15 (s, 1 H), 5.53 (s, 1 H), 5.85 (d, J = 6.8 Hz, (m, 1 H), 7.27 (d, J = 8.0 Hz, 2 H), 7.40–7.44 (m, 2 H), 7.56–7.58
1 H), 6.32–6.36 (m, 1 H), 6.59 (s, 1 H), 6.81 (d, J = 6.8 Hz, 1 H),
(m, 3 H), 8.12 (d, J = 8.0 Hz, 1 H) ppm. 13C NMR ([D6]DMSO,
7.10 (d, J = 8.8 Hz, 1 H), 7.21–7.49 (m, 7 H), 7.63 (d, J = 8.8 Hz, 100 MHz): δC = 13.6, 36.7, 46.4, 56.2, 57.1, 108.7, 109.1, 109.7,
1 H), 7.73 (d, J = 7.6 Hz, 1 H), 8.09 (d, J = 8.0 Hz, 1 H) ppm. 13C
NMR ([D6]DMSO, 100 MHz): δC = 17.0, 46.0, 56.2, 56.7, 110.0,
117.4, 118.3, 119.3, 121.2, 122.3, 122.6, 126.6, 127.1, 127.7, 128.0,
128.2, 128.7, 128.9, 129.4, 134.0, 141.2, 143.5, 145.6, 148.9 ppm.
113.2, 115.3, 116.8, 118.2, 120.4, 121.0, 121.3, 122.3, 124.7, 125.0,
127.7, 129.5, 130.8, 131.0, 133.2, 139.6, 141.5, 150.2, 159.6 ppm.
HRMS (ESI): calcd. for C29H25BrN3 [M + H]+ 494.1232; found
494.1214.
6
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A Stereoselective Povarov Reaction
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General Procedure for the Synthesis of 3-[(Aryl)(1-methyl-1H-indol-
3-yl)methyl]-1-methyl-1H-indole Derivatives 5: Aromatic aldehyde
(1.0 mmol), naphthalen-2-amine (0.143 g, 1.0 mmol), indole
(1.0 mmol), I2 (0.013 g, 0.05 mmol), and toluene (10 mL) were
added to a 50 mL flask. The reaction mixture was stirred at room
temperature until it reached completion. Reaction progress was
monitored by TLC. Products 5 were purified by column
chromatography using ethyl acetate/petroleum ether (1:6) as eluent.
[3]
[4]
3-[(4-Methoxyphenyl)(1-methyl-1H-indol-3-yl)methyl]-1-methyl-1H-
indole (5a): Yield 92% (350 mg). Pale yellow solid, m.p. 215–216 °C
(Lit.[16a]: 218–219 °C). 1H NMR ([D6]DMSO, 400 MHz): δH = 3.69
(s, 6 H), 3.71 (s, 3 H), 5.78 (s, 1 H), 6.79 (s, 2 H), 6.84 (d, J =
8.0 Hz, 2 H), 6.89–6.93 (m, 2 H), 7.11 (t, J = 7.6 Hz, 2 H), 7.26 (d,
J = 7.6 Hz, 2 H), 7.30 (d, J = 8.0 Hz, 2 H), 7.37 (d, J = 8.0 Hz, 2
H) ppm. 13C NMR ([D6]DMSO, 100 MHz): δC = 32.2, 38.5, 54.9,
109.5, 113.4, 117.7, 118.2, 119.2, 121.0, 126.9, 127.8, 129.1, 136.7,
137.0, 157.3 ppm. HRMS (ESI): calcd. for C26H24N2ONa [M +
Na]+ 403.1786; found 403.1797.
[5]
[6]
3-[(4-Chlorophenyl)(1-methyl-1H-indol-3-yl)methyl]-1-methyl-1H-
indole (5b): Yield 90% (347 mg). Pale yellow solid, m.p. 206–208 °C
(Lit.[16a]: 208–209 °C). 1H NMR ([D6]DMSO, 400 MHz): δH = 3.70
(s, 6 H), 5.87 (s, 1 H), 6.83 (s, 2 H), 6.91–6.94 (m, 2 H), 7.12 (t, J
= 7.6 Hz, 2 H), 7.29–7.39 (m, 8 H) ppm. 13C NMR ([D6]DMSO,
100 MHz): δC = 32.2, 38.6, 109.6, 116.8, 118.4, 119.1, 121.1, 126.7,
127.9, 128.0, 130.0, 130.4, 137.0, 143.8 ppm. HRMS (ESI): calcd.
for C25H21ClN2Na [M + Na]+ 407.1291; found 407.1297.
3-[(4-Fluorophenyl)(1-methyl-1H-indol-3-yl)methyl]-1-methyl-1H-
indole (5c): Yield 89% (328 mg). Pale yellow solid, m.p. 198–200 °C.
1H NMR ([D6]DMSO, 400 MHz): δH = 3.70 (s, 6 H), 5.87 (s, 1 H),
6.82 (s, 2 H), 6.90–6.94 (m, 2 H), 7.08 (d, J = 9.2 Hz, 2 H), 7.12
(d, J = 8.0 Hz, 2 H), 7.30 (d, J = 8.0 Hz, 2 H), 7.36–7.39 (m, 4 H)
ppm. 13C NMR ([D6]DMSO, 100 MHz): δC = 32.2, 38.5, 54.9,
109.5, 113.4, 117.7, 118.2, 119.2, 121.0, 126.9, 127.8, 129.1, 136.7,
137.0, 157.3 ppm. HRMS (ESI): calcd. for C25H21FN2Na [M +
Na]+ 391.1586; found 391.1582.
[7]
[8]
Supporting Information (see footnote on the first page of this arti-
cle): NMR spectra of compounds 4a–u and 5a–c.
Acknowledgments
We are grateful to the Priority Academic Program Development of
Jiangsu Higher Education Institutions, the National Natural Sci-
ence Foundation of China (20802061), and a Qing Lan Project of
the Jiangsu Education Committee (08QLT001 and (10QLD008) for
financial support.
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X.-S. Wang, M.-Y. Yin, W. Wang, S.-J. Tu
FULL PAPER
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Received: April 26, 2012
Published Online: ᭿
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Date: 18-07-12 17:48:54
Pages: 9
A Stereoselective Povarov Reaction
Three-Component Reactions
X.-S. Wang,* M.-Y. Yin, W. Wang,
S.-J. Tu ............................................. 1–9
A Stereoselective Povarov Reaction Lead-
ing to exo-Tetrahydroindolo[3,2-c]quinol-
ine Derivatives Catalyzed by Iodine
Keywords: Multicomponent reactions
Homogeneous catalysis / Iodine / Dia-
stereoselectivity / Heterocycles
/
exo-Indolo[3,2-c]quinoline derivatives re-
lated to the alkaloid isocryptolepine
(cryptosanguinolentine) were synthesized
by an iodine-catalyzed Povarov reaction.
This procedure has the advantages of good
yield and high stereoselectivity.
Eur. J. Org. Chem. 0000, 0–0
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