Convenient, two-step synthesis of 2-styrylquinolines: an application of the CAN-catalyzed vinylogous type-II Povarov reaction

Article abstract of DOI:10.1016/j.tet.2008.12.077

A new, experimentally simple, synthesis of 2-styrylquinolines was developed using a two-step sequence based on a CAN-catalyzed three-component type-II vinylogous Povarov reaction from arylamines, cinnamaldehydes, and electron-rich cyclic and noncyclic vin

Full text of DOI:10.1016/j.tet.2008.12.077

Tetrahedron 65 (2009) 2087–2096
Contents lists available at ScienceDirect
Tetrahedron
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Convenient, two-step synthesis of 2-styrylquinolines: an application
of the CAN-catalyzed vinylogous type-II Povarov reaction
*
´
Vellaisamy Sridharan, Carmen Avendan˜o, J. Carlos Menendez
´
´
Departamento de Qu´ımica Organica y Farmaceutica, Facultad de Farmacia, Universidad Complutense, 28040 Madrid, Spain
a r t i c l e i n f o
a b s t r a c t
Article history:
A new, experimentally simple, synthesis of 2-styrylquinolines was developed using a two-step sequence
based on a CAN-catalyzed three-component type-II vinylogous Povarov reaction from arylamines, cin-
namaldehydes, and electron-rich cyclic and noncyclic vinyl ethers. The tetrahydroquinolines thus ob-
tained were subsequently aromatized to styrylquinolines by DDQ-promoted dehydrogenation.
Ó 2009 Elsevier Ltd. All rights reserved.
Received 19 November 2008
Received in revised form 22 December 2008
Accepted 26 December 2008
Available online 8 January 2009
1. Introduction
functionalized tetrahydroquinolines11 and also report our studies
on their aromatization to styrylquinolines. This methodology is
The quinoline ring system1 is an essential structural fragment of
a large number of natural and unnatural compounds possessing
a wide variety of pharmacological actions,2,3 in addition to their
application in materials science.4,5 Amongst quinoline derivatives,
there is much current interest in 2-styrylquinolines (SQLs), exem-
plified by FZ41 and KHD161 (Fig. 1). These compounds are normally
devoid of significant cytotoxicity and provide a novel and promis-
ing strategy for AIDS therapy6 due to their ability to act as HIV
integrase inhibitors7 by a previously unknown mechanism.8
The available methods for the synthesis of styrylquinolines are
based on the synthesis of 2-methylquinolines followed by an acid
or base catalyzed condensation with suitable aromatic aldehy-
des,7a–d,9 in which the final step is not a facile one and gives
moderate yields in many cases. Syntheses of the key intermediate
2-methylquinolines have been normally achieved by traditional
methods like the Friedla¨nder, Doebner–von Miller, Combes, and
Pfitzinger reactions. In spite of their simplicity, these methods have
considerable drawbacks such as low yields and the use of harsh
reaction conditions and highly acidic reaction media, although
some new procedures and improvements of the classical reactions
have been reported.10 Consequently, it is still important to develop
a simple and efficient alternative synthetic route to the valuable
styrylquinolines.
based on a novel three-component reaction between arylamines,
vinyl ethers, and cinnamaldehyde catalyzed by cerium(IV) am-
monium nitrate (CAN), which is a nontoxic, inexpensive, and
water-tolerant reagent that has found widespread use in carbon–
carbon and carbon–heteroatom bond forming reactions12 but has
received relatively little attention as a catalyst.13 The first step in
our protocol (Scheme 1) is a type-II vinylogous Povarov reaction11
between an arylamine and cinnamaldehyde. This reaction involves
the formation of an a,b-unsaturated imine as an intermediate, and
this mechanism is the origin of the main potential drawback of our
planned approach, namely the fact that cinnamaldehyde aryl-
imines possess an exocyclic
a,b-unsaturated imine system that
may act as a diene in inverse electron demand Diels–Alder
reactions with electron-rich dienophiles, leading to 1,4-dihydro-
pyridines.14 On the other hand, some nucleophilic 1,2-additions of
ketene silyl ketals and thioketals to
a,b-unsaturated arylimines
have been described,15 providing an encouraging, although re-
mote, precedent because such an addition can be considered to be
the first step of our proposed transformation (Scheme 1), as it is
now generally accepted that the Povarov reaction normally pro-
ceeds stepwise.13e,16,17
R1
HO2C
N
2. Results and discussion
OH
OH
In this context, we extend and generalize here the results in
our recent preliminary communication on the synthesis of 2-
OR
R = CH3; R1 = OH
FZ41
KHD161 R = H; R1 = H
* Corresponding author. Tel.: þ34 91 3941840; fax: þ34 91 3941822.
´
Figure 1.
E-mail address: josecm@farm.ucm.es (J. Carlos Menendez).
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.12.077

2088
V. Sridharan et al. / Tetrahedron 65 (2009) 2087–2096
Table 1
D
CAN-catalyzed synthesis of 3,3a,4,5,9b-hexahydro-4-styrylfuro[3,2-c]quinolines
R
R
R
Compd
R1
R2
R3
R4
Reaction
time (h)
Yield (%)
4/5 Ratioa
N
H
Ar
N
Ar
a
b
c
d
e
f
H
H
H
H
H
H
CH3
H
H
H
H
H
CH3
H
H
Cl
CH3
Br
F
H
H
H
H
H
CH3
H
2
2
4
1.5
4
83
80
68
79
70
75
85
57:43
54:46
60:40
53:47
54:46
55:45
53:47
Type II vinylogous
Povarov reaction
D
Required
Ar
H
CH3
2
6
NH2
O
g
R
a
Ar
N
This product ratio was calculated from the 1H NMR spectrum of the crude re-
action mixture and both products were subsequently separated by column
chromatography.
Scheme 1.
postulated in the above mentioned stepwise mechanism. Indeed,
when the reaction starting from p-chloroaniline, cinnamaldehyde,
and butyl vinyl ether was carried out in ethanol, a nucleophilic
solvent, tetrahydroquinoline 7f was accompanied by an almost
equimolecular amount of acetal 9, arising from a four-component
process involving trapping of the oxonium intermediate by a sol-
vent molecule (Scheme 5). This behavior was similar to the one
previously found by us for the non-vinylogous CAN-catalyzed
Povarov reaction.13b
Finally, in an effort to clarify whether CAN exerts its role in our
2-styryl-1,2,3,4-tetrahydroquinoline synthesis through an oxida-
tive pathway, as might be expected from a powerful one-electron
oxidant, we performed the reaction between cinnamaldehyde,
aniline, and ethyl vinyl ether (entry 1 in Table 2) in the presence of
a large amount of 1,1-diphenylethylene, a well-known radical trap,
finding no noticeable loss in yield. This result indicates that a radi-
cal mechanism is not in operation under our conditions and that
therefore in this case CAN acts as a Lewis acid, a behavior that has
some precedent in the literature.13a–d,20
With an efficient methodology for the synthesis of the in-
termediate tetrahydroquinolines in hand, we next examined their
dehydrogenation into styrylquinolines. While the literature con-
tains some examples of aromatization of 4-alkoxy-1,2,3,4-tetra-
hydroquinolines in acidic media, we had previously obtained
product mixtures using this approach.10 Therefore, anchored in our
previous experience in the aromatization of 2-methyl-1,2,3,4-tet-
rahydroquinolines to the corresponding 2-methylquinolines,10 we
initially employed 10% activated Pd/C for the aromatization process.
When some mixtures of compounds 4 and 5 were refluxed in
methanol containing suspended 10% Pd/C, only the endo isomers 4
were converted into styrylquinolines 10, with concomitant opening
of the furan ring, whereas the exo isomers 5 remained unreacted
(Scheme 6, Table 3). An increase of the Pd/C load and reaction time
did not improve these results.
In the event, our starting hypothesis turned out to be correct and
the desired vinylogous reaction could be carried out efficiently by
mixing together anilines 1, cinnamaldehyde 3 and 2,3-dihydrofuran 2
as a prototype cyclic ether in acetonitrile with a catalytic amount of
CAN (5%), and led to 2,3,3a,4,5,9b-hexahydro-4-styrylfuro[3,2-
c]quinoline derivatives (compounds 4 and 5) in good to excellent
yields, as almost equimolecular mixtures of diastereomers. The re-
actions proceeded well with both electron donating and withdrawing
groups in the arylamine component (Scheme 2 and Table 1), although
some substituents (specially alkoxy groups) disappointingly led to
complex mixtures. These reactions have no significant stereo-
selectivity, as expected from literature precedent on straightforward
Povarov reactions of cyclic vinyl ethers.13b,18 The stereochemistry of
the products was unambiguously determined by the combined use of
coupling constant values and NOESY experiments.
In order to generalize the new synthesis of 2-styryl-1,2,3,4-tetra-
hydroquinolines, we explored the use of noncyclic vinyl ethers 6,
which so far has received little attention in Povarov chemistry
(Scheme 3, Table 2). It is interesting to note that the reaction was
completely diastereoselective and gave only 2-styryl-1,2,3,4-tetra-
hydroquinolines 7 with a cis arrangement between H-2 and H-4.
The yields were lower than in the reactions involving cyclic vinyl
ethers due to the formation of side product identified as 2-methyl-
1,2,3,4-tetrahydroquinolines 8, which can be explained by a CAN-
catalyzed three-component reaction between arylamines and two
molecules of vinyl ether.10
The complete diastereoselectivity found for the reactions
starting from noncyclic vinyl ethers 6 can be explained by assuming
a stepwise mechanism for the vinylogous Povarov reaction, where
a cis arrangement between the alkoxy and styryl groups leads to
minimum interactions between these bulky substituents and the
axial protons in the chair-like transition state of the cyclization step
leading to the tetrahydroquinoline system (Scheme 4).
In order to provide further support for this explanation, we
considered it relevant to confirm whether our imino Diels–Alder
reaction took place in a concerted or stepwise manner since, al-
though the mechanism of the Povarov reaction is normally ac-
cepted to be stepwise,16 there is also evidence pointing at concerted
pathways in some cases.19 For this reason, we wished to verify the
generation of the putative intermediate oxonium species
The stereoselective dehydrogenation of the endo isomer 4 can be
explained by admitting that coordination to palladium takes place
preferentially on the less hindered H-3a and H-4 hydrogens and that
this coordination is expected to be more favorable in 4 than 5, where
both hydrogens have a trans relationship. A subsequent elimination
reaction involving the oxygen atom of the tetrahydrofuran ring as
a leaving group explains the isolation of compounds 10 (Scheme 7).
O
R4
O
R4
R1
O
H
H
R3
R2
R4
R3
R2
2
H
R3
R2
CAN (5 mol%), CH3CN, rt
H
H
+
N
Ph
N
Ph
H
O
H
R1
5 (exo)
H
H
NH2
R1
1
4 (endo)
3
Scheme 2.

V. Sridharan et al. / Tetrahedron 65 (2009) 2087–2096
2089
OR4
OR4
OR4
R2
R3
R2
6
H
R2
R3
CAN (5-15%), CH3CN
+
O
NH2
N
H
N
H
CH3
R1
R1
R1
2
1
7
8
Scheme 3.
R1
Table 2
Type-II vinylogous Pavarov reaction with noncyclic vinyl ethers
O
H
R2
R3
R1
R2
R3
R4
CAN (mol %)
Time (h)
Yield (%)
H
Comp
R1
N
Ph
O
7
8
H
H
H
R2
R3
Pd/C
MeOH, reflux
5
a
b
c
d
e
f
g
h
i
H
H
H
H
H
H
H
H
H
H
OCH3
H
H
H
H
Cl
Cl
Cl
F
H
H
H
H
H
H
H
H
H
H
H
NO2
Et
Pr
Bu
Et
Pr
Bu
Et
Bu
Et
Et
Et
Et
5
5
5
5
5
3
3
3
2
2
2
2
2
60
63
65
48
55
49
40
41
46
60
53
41
6
5
3
H
+
R1
N
Ph
H
R2
R3
OH
Ph
13
13
15
16
18
16
4 + 5
5
N
10
15
15
5
15
15
5
F
Br
CH3
H
1.5
5
1
Scheme 6. Aromatization of endo/exo mixtures of furo[3,2-c]quinolines 4 and 5 in the
j
k
l
3a
presence of Pd/C.
32
5
H
1
Table 3
Results obtained in the aromatization of mixtures of 4 and 5 in the presence of Pd/C
a
Together with 15% of the corresponding aromatized styrylquinoline.
Compd
R1
R2
R3
Initial 4/5
Reaction
time (h)
Final 5/10
ratio
ratioa
a
c
f
H
H
CH3
H
CH3
H
H
H
CH3
57:43
60:40
55:45
6
6
6
46:54
36:64
43:57
OR2
6
R1
Product ratio was determined from the crude 1H NMR spectrum of the reaction
a
Ce (IV)
1
+
3
mixture.
N
3
Ce (IV)
2
9b
H
O
1
3a
5
4
O
9a
9
7
- Ce (IV)
H
Ph
N
H
8
10
Pd
5a
R2O
- H2
R2O
6
H
N
Ph
H
N
H
R1
4 (endo)
N
R1
H
H
H
H
Scheme 7. Explanation for the stereospecific dehydrogenation of the endo isomer of
compound 4.
7
Scheme 4. Stepwise mechanism proposed for the type-II vinylogous Povarov reaction.
In an effort to improve these results, we investigated the aro-
matization reaction in the presence of the well-known oxidizing
agent DDQ (Scheme 8, Table 4). Treatment of diastereomeric mix-
tures of 4 and 5 in benzene with 2 equiv of DDQ under mild con-
ditions (room temperature) afforded mixtures of isomeric
styrylquinolines 10 and 11 in excellent overall yields and in ca. 2:1
ratios, in a reaction that proceeded very well irrespectively of the
nature of the substituents.
OCH2CH2CH2CH3
Cl
O
+
NH2
H
DDQ was also employed for the aromatization of tetrahy-
droquinolines 7. As expected, the reaction proceeded smoothly to
give styrylquinolines 12 in excellent yields and under mild
CAN (5 mol %), C2H5OH
OCH2CH2CH2CH3
Cl
R4
R3
R2
OH
Ph
N
H
C2H5OH
N
R1
10
DDQ (2 eq.)
benzene, r.t.
OCH2CH2CH2CH3
+
H3CH2CO
OCH2CH2CH2CH3
4 + 5
Cl
R4
Cl
O
R3
R2
N
H
N
H
N
Ph
7f (41%)
9 (30%)
R1
11
Scheme 8. Aromatization of mixtures of compounds 4 and 5 in the presence of DDQ.
Scheme 5. CAN-catalyzed one-pot reaction of 4-chloroaniline, cinnamaldehyde, and
butyl vinyl ether in ethanol.

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V. Sridharan et al. / Tetrahedron 65 (2009) 2087–2096
Table 4
R
DDQ-mediated aromatization of mixtures of compounds 4 and 5
OEt
N
12
Ph
Compd
R1
R2
R3
R4
Yield (%)
10/11 Ratioa
R
a
b
c
d
e
f
H
H
H
H
H
H
H
H
H
H
H
CH3
H
H
H
H
H
H
CH3
97
96
94
96
97
95
68:32
66:34
68:32
61:39
68:32
70:30
CAN (2.5 eq.)
Ph
CH3CN, 0 °C
Cl
CH3
Br
F
+
N
H
R
7
N
Ph
H
NO2
a
Product ratio was calculated from the 1H NMR spectrum of the crude reaction
13
mixture and products were separated by column chromatography.
Scheme 10. Exploratory study of the CAN-mediated aromatization of compounds 7.
conditions (Scheme 9, Table 5). In two cases (entries 9 and 10) we
used the crude tetrahydroquinolines, obtained in the previous re-
action, for the second aromatization step. Products were isolated
without any significant loss of yield with regard to the cases where
pure tetrahydroquinolines were used as starting materials.
Table 6
Results obtained in the CAN-mediated aromatization of 7
Entry
Starting compd
R
Yield of 12 (%)
Yield of 13 (%)
1
2
3
4
7d
7d
7g
7j
Cl
C
F
95
45
94
35
0
0a
0
R4
R4 OR5
R3
R2
R3
R2
CH3
59
DDQ (2 eq.)
benzene, r.t.
a
This reaction was performed in a one-pot procedure from 4-chloroaniline, cin-
namaldehyde, and ethyl vinyl ether.
N
N
H
R1
R1
R6
R6
12
7
Scheme 9. Aromatization of tetrahydroquinolines 7 in the presence of DDQ.
the preparation of 8-nitroquinolines, which are important in-
termediates in the preparation of several families of bioactive
quinoline systems.24
Table 5
Results obtained in the DDQ-mediated aromatization of 7
3. Conclusion
Entry
R1
R2
R3
R4
R5
R6
Yield (%)
Product
1
2
3
4
5
6
7
8
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
Cl
Br
F
CH3
H
H
H
H
H
H
H
H
H
Et
Pr
Bu
Et
Et
Et
Et
Et
Et
Et
H
H
H
H
H
H
H
NO2
H
96
95
94
97
95
94
90
94
87b
84b
12a
12a
12a
12b
12c
12d
12e
12f
In conclusion, we have developed an efficient two-reaction se-
quence that provides synthetic entry into biologically relevant 2-
styrylquinolines based on a new CAN-catalyzed type-II vinylogous
Povarov reaction and a DDQ-mediated aromatization. This meth-
odology requires mild conditions and employs very simple starting
materials and inexpensive and easily handled catalysts.
9a
10a
H
CH3
CH3
H
H
CH3
CH3
H
12g
12h
4. Experimental
4.1. General
H
a
Tetrahydroquinoline 7 was not separated. The crude obtained in the previous
reaction, containing a mixture of quinoline and tetrahydroquinoline, was directly
treated with 1 equiv of DDQ.
b
Overall yield from the corresponding anilines.
All reagents (Aldrich, Fluka, SDS, Probus) and solvents (SDS,
Scharlau) were of commercial quality and were used as received.
Reactions were monitored by TLC on aluminum plates coated with
silica gel with fluorescent indicator (SDS CCM221254). Separations
by flash chromatography were performed on silica gel (SDS 60 ACC
40–63 mm). Melting points were measured on a Reichert 723 hot
stage microscope and are uncorrected. Infrared spectra were
recorded on a Perkin Elmer Paragon 1000 FT-IR spectrophotometer
with all compounds examined as thin films on NaCl disks. NMR
spectra were obtained on a Bruker Avance 250 spectrometer op-
erating at 250 and 62.9 MHz for 1H and 13C NMR spectra, re-
Finally, and due to the existence of a literature precedent for
a CAN-mediated aromatization of tetrahydroquinolines,21 we set
out to study the use of this reagent to achieve the aromatization
step because, if successful, this reaction would pave the way for
a one-pot synthesis of 2-styrylquinolines from simple acyclic pre-
cursors. We carried out some exploratory experiments involving
treatment of 2-styryltetrahydroquinolines with 2.5 equiv of CAN in
acetonitrile at 0 ꢀC, and found that compounds containing electron-
withdrawing groups (7d and 7g) afforded the expected
styrylquinolines (12b and 12d) in excellent yields. However, com-
pounds with an electron-donating group (7j) gave a 1:2 mixture of
the expected styrylquinoline 12 and its 8-nitro derivative (13)
(Scheme 10, Table 6). Interestingly, since both the aza Diels–Alder
and the aromatization reactions are promoted by CAN, they can be
performed in a one-pot procedure without any noticeable loss of
yield (entry 2 of Table 6).
´
spectively (CAI de Resonancia Magnetica Nuclear, Universidad
Complutense), with the signal of the residual non-deuterated sol-
vent as an internal standard. Combustion elemental analyses were
´
determined by the CAI de Microanalisis Elemental, Universidad
Complutense, using a Leco 932 CHNS microanalyzer.
4.2. General procedure for the CAN-catalyzed synthesis of
2,3,3a,4,5,9b-hexahydro-4-styrylfuro[3,2-c]quinolines (4, 5)
While CAN is a relatively well-known reagent for the nitration of
electron-rich aromatic substrates,22 very often in acidic media or on
solid supports,23 this regioselective nitration of a quinoline de-
rivative at its C-8 position is remarkable, and can be probably at-
tributed to coordination of Ce(IV) to the quinoline nitrogen. We are
currently studying the scope of this reaction as a new method for
An equimolar (3 mmol) mixture of arylamine (1) and cinna-
maldehyde (2) was dissolved in acetonitrile (20 mL) and stirred at
room temperature. To this stirred solution, dihydrofuran,
3
(4.5 mmol), and 5 mol % of CAN were added, and stirring was
continued for the time period specified in Table 1. After completion

V. Sridharan et al. / Tetrahedron 65 (2009) 2087–2096
2091
of the reaction, as indicated by TLC, the mixture was extracted with
dichloromethane (2ꢁ20 mL), dried (anhydrous Na2SO4), and
evaporated. The ratio of endo and exo 2,3,3a,4,5,9b-hexahydro-2-
styrylfuro[3,2-c]quinolines (4, 5) was calculated from the 1H NMR
spectrum of the crude reaction mixture, and the products were
separated through silica column using petroleum ether/ethyl ace-
tate mixture (98:2 to 95:5, v/v).
131.1, 131.7, 137.1, 142.4. Anal. Calcd for C20H21NO: C, 82.44; H, 7.26;
N, 4.81. Found: C, 82.19; H, 7.11; N, 4.70.
4.2.6. exo-2,3,3a,4,5,9b-Hexahydro-8-methyl-4-styrylfuro-
[3,2-c]quinoline 5c
Viscous liquid. IR (neat) 3334.4, 3016.9, 2862.0, 1621.2, 1508.0,
1353.4, 1264.4, 1128.1, 1042.6 cmꢂ1 1H NMR (CDCl3, 250 MHz)
.
d
1.95–2.00 (m, 1H), 2.13–2.29 (m, 2H), 2.34 (s, 3H), 3.44 (dd, J¼10.0,
4.2.1. endo-2,3,3a,4,5,9b-Hexahydro-4-styrylfuro[3,2-c]quinoline 4a
8.7 Hz, 1H), 3.85–4.06 (m, 3H), 4.60 (d, J¼5.0 Hz, 1H), 6.24 (dd,
J¼15.8, 8.5 Hz, 1H), 6.61 (d, J¼8.1 Hz, 1H), 6.69 (d, J¼15.8 Hz, 1H),
6.98 (dd, J¼8.1, 1.8 Hz, 1H), 7.23 (d, J¼1.8 Hz, 1H), 7.29–7.49 (m, 5H).
Viscous liquid. IR (neat) 3327.2, 3024.0, 2875.2, 1609.3, 1484.2,
1364.6, 1259.6, 1063.4 cmꢂ1. 1H NMR (CDCl3, 250 MHz)
d 2.03–2.22
(m, 2H), 2.73–2.84 (m, 1H), 3.82–3.88 (m, 3H), 4.19 (dd, J¼7.8,
3.5 Hz,1H), 5.13 (d, J¼7.3 Hz,1H), 6.35 (dd, J¼15.8, 7.8 Hz,1H), 6.61–
6.71 (m, 2H), 6.85 (td, J¼7.5, 0.9 Hz, 1H), 7.14 (td, J¼7.5, 0.9 Hz, 1H),
13C NMR (CDCl3, 62.9 MHz)
d 20.9, 29.4, 42.2, 56.7, 65.7, 76.2, 115.3,
120.7, 126.9, 128.2, 128.4, 129.1, 130.2, 130.3, 131.7, 133.8, 136.8,
142.7. Anal. Calcd for C20H21NO: C, 82.44; H, 7.26; N, 4.81. Found: C,
82.28; H, 7.25; N, 4.75.
7.27–7.47 (m, 6H). 13C NMR (CDCl3, 62.9 MHz)
d 26.1, 43.1, 56.2, 66.9,
75.9, 115.4, 119.4, 122.3, 126.9, 128.3, 129.0, 129.2, 130.2, 130.8, 131.8,
137.1, 144.7. Anal. Calcd for C19H19NO: C, 82.28; H, 6.90; N, 5.05.
Found: C, 81.92; H, 6.78; N, 5.00.
4.2.7. endo-8-Bromo-2,3,3a,4,5,9b-hexahydro-4-styrylfuro-
[3,2-c]quinoline 4d
Viscous liquid. IR (neat) 3328.0, 3024.8, 2873.8, 1597.8, 1486.4,
4.2.2. exo-2,3,3a,4,5,9b-Hexahydro-4-styrylfuro[3,2-c]quinoline 5a
1333.6, 1295.5, 1259.0, 1178.8, 1063.4 cmꢂ1 1H NMR (CDCl3,
.
Viscous liquid. IR (neat) 3333.8, 3024.6, 2861.3, 1611.3, 1482.8,
250 MHz) d 2.04–2.21 (m, 2H), 2.72–2.76 (m, 1H), 3.81–3.87 (m,
1363.1, 1264.0, 1127.0, 1042.2 cmꢂ1
d
.
1H NMR (CDCl3, 250 MHz)
2H), 4.16 (dd, J¼7.8, 3.5 Hz, 1H), 5.04 (d, J¼7.3 Hz, 1H), 6.29 (dd,
J¼15.8, 7.9 Hz, 1H), 6.48 (d, J¼8.6 Hz, 1H), 6.66 (d, J¼15.8 Hz, 1H),
7.19 (dd, J¼8.6, 2.3 Hz, 1H), 7.27–7.49 (m, 6H). 13C NMR (CDCl3,
1.91–2.01 (m, 1H), 2.20–2.35 (m, 2H), 3.48 (dd, J¼9.7, 8.9 Hz, 1H),
3.84–3.94 (m, 1H), 4.01–4.11 (m, 2H), 4.64 (d, J¼4.8 Hz, 1H), 6.24
(dd, J¼15.8, 8.5 Hz, 1H), 6.67–6.73 (m, 2H), 6.84 (td, J¼7.4, 0.8 Hz,
1H), 7.17 (td, J¼7.4, 0.8 Hz, 1H), 7.28–7.49 (m, 6H). 13C NMR (CDCl3,
62.9 MHz)
d 25.8, 42.8, 55.9, 67.0, 75.3, 110.9, 116.9, 124.3, 126.9,
128.4, 129.1, 129.5, 131.7, 132.2, 133.2, 136.8, 143.6. Anal. Calcd for
C19H18BrNO: C, 64.06; H, 5.09; N, 3.93. Found: C, 63.78; H, 5.00; N,
3.81.
62.9 MHz)
d 29.4, 41.9, 56.3, 65.7, 76.2, 115.4, 118.9, 120.6, 127.0,
128.5, 129.2, 129.5, 130.2, 131.7, 133.9, 136.8, 145.2. Anal. Calcd for
C19H19NO: C, 82.28; H, 6.90; N, 5.05. Found: C, 82.01; H, 6.81; N,
4.96.
4.2.8. exo-8-Bromo-2,3,3a,4,5,9b-hexahydro-4-styrylfuro-
[3,2-c]quinoline 5d
4.2.3. endo-8-Chloro-2,3,3a,4,5,9b-hexahydro-4-styrylfuro[3,2-c]-
quinoline 4b
Viscous liquid. IR (neat) 3384.8, 3024.8, 2875.7, 1601.2, 1488.4,
1351.8, 1265.4, 1128.0, 1043.0 cmꢂ1 1H NMR (CDCl3, 250 MHz)
.
Viscous liquid. IR (neat) 3327.9, 3023.3, 2877.6, 1603.8, 1489.3,
d
1.92–1.99 (m, 1H), 2.13–2.32 (m, 2H), 3.44 (dd, J¼9.4, 9.1 Hz, 1H),
1295.5, 1259.4, 1063.9 cmꢂ1. 1H NMR (CDCl3, 250 MHz)
d
2.01–2.21
3.81–4.10 (m, 3H), 4.56 (d, J¼4.8 Hz, 1H), 6.20 (dd, J¼15.8, 8.5 Hz,
1H), 6.55 (d, J¼8.6 Hz, 1H), 6.69 (d, J¼15.8 Hz, 1H), 7.22 (dd, J¼8.6,
(m, 2H), 2.69–2.80 (m, 1H), 3.81–3.87 (m, 3H), 4.17 (dd, J¼7.9,
3.6 Hz, 1H), 5.04 (d, J¼7.3 Hz, 1H), 6.30 (dd, J¼15.8, 7.9 Hz, 1H), 6.53
(d, J¼8.6 Hz, 1H), 6.67 (d, J¼15.8 Hz,1H), 7.06 (dd, J¼8.6, 2.4 Hz,1H),
2.3 Hz, 1H), 7.28–7.51 (m, 6H). 13C NMR (CDCl3, 62.9 MHz)
d 29.3,
41.7, 56.3, 65.7, 75.6, 110.3, 116.9, 122.6, 126.9, 128.5, 129.2, 129.6,
132.2, 134.1, 134.3, 136.6, 144.1. Anal. Calcd for C19H18BrNO: C,
64.06; H, 5.09; N, 3.93. Found: C, 63.90; H, 5.01; N, 3.88.
7.26–7.45 (m, 6H). 13C NMR (CDCl3, 62.9 MHz)
d 25.8, 42.8, 56.0,
67.0, 75.4, 116.5, 123.7, 123.8, 126.9, 128.4, 128.9, 129.1, 129.6, 130.3,
132.2, 136.8, 143.1. Anal. Calcd for C19H18ClNO: C, 73.19; H, 5.82; N,
4.49. Found: C, 73.02; H, 5.67; N, 4.30.
4.2.9. endo-8-Fluoro-2,3,3a,4,5,9b-hexahydro-4-styrylfuro-
[3,2-c]quinoline 4e
4.2.4. exo-8-Chloro-2,3,3a,4,5,9b-hexahydro-4-styrylfuro[3,2-c]-
quinoline 5b
Viscous liquid. IR (neat) 3332.1, 3027.3, 2876.1, 1598.5, 1499.5,
1315.3, 1247.6, 1151.7, 1062.9 cmꢂ1 1H NMR (CDCl3, 250 MHz)
.
Viscous liquid. IR (neat) 3330.3, 3025.3, 2875.7, 1606.9, 1491.1,
d 2.01–2.23 (m, 2H), 2.70–2.81 (m, 1H), 3.77–3.88 (m, 3H), 4.16 (dd,
1351.9, 1264.9, 1127.8, 1043.2 cmꢂ1
d
.
1H NMR (CDCl3, 250 MHz)
J¼7.8, 3.5 Hz, 1H), 5.07 (d, J¼7.4 Hz, 1H), 6.32 (dd, J¼15.8, 7.8 Hz,
1H), 6.55 (dd, J¼8.8, 4.7 Hz, 1H), 6.68 (d, J¼15.8 Hz, 1H), 6.85 (td,
J¼8.6, 2.9 Hz, 1H), 7.10 (dd, J¼9.1, 2.9 Hz, 1H), 7.27–7.46 (m, 5H). 13C
1.95–2.02 (m, 1H), 2.16–2.32 (m, 2H), 3.43 (dd, J¼9.5, 9.0 Hz, 1H),
3.81–3.92 (m, 1H), 3.99–4.15 (m, 1H), 4.18 (br s, 1H), 4.56 (d,
J¼4.8 Hz, 1H), 6.21 (dd, J¼15.8, 8.5 Hz, 1H), 6.60 (d, J¼8.6 Hz, 1H),
6.69 (d, J¼15.8 Hz, 1H), 7.11 (dd, J¼8.6, 2.4 Hz, 1H), 7.29–7.49 (m,
NMR (CDCl3, 62.9 MHz)
d
25.5, 42.7, 56.1, 66.8, 75.4 (d, J¼1.0 Hz),
115.7 (d, J¼19.1 Hz), 116.0 (d, J¼3.6 Hz), 116.3 (d, J¼21.7 Hz), 123.3
(d, J¼6.3 Hz), 126.6, 128.1, 128.9, 129.6, 131.7, 136.7, 140.6 (d,
J¼1.8 Hz),156.1 (d, J¼236.5 Hz). Anal. Calcd for C19H18FNO: C, 77.27;
H, 6.14; N, 4.74. Found: C, 77.01; H, 6.03; N, 4.62.
6H). 13C NMR (CDCl3, 62.9 MHz)
d 29.3, 41.8, 56.4, 65.7, 75.7, 116.5,
122.1, 123.2, 126.9, 128.6, 129.2, 129.4, 129.7, 131.2, 134.2, 136.7,
143.7. Anal. Calcd for C19H18ClNO: C, 73.19; H, 5.82; N, 4.49. Found:
C, 72.88; H, 5.64; N, 4.40.
4.2.10. exo-8-Fluoro-2,3,3a,4,5,9b-hexahydro-4-styrylfuro-
[3,2-c]quinoline 5e
4.2.5. endo-2,3,3a,4,5,9b-Hexahydro-8-methyl-4-styrylfuro[3,2-c]-
quinoline 4c
Viscous liquid. IR (neat) 3329.4, 3029.7, 2872.1, 1598.5, 1501.7,
Viscous liquid. IR (neat) 3324.0, 3022.9, 2869.4, 1619.1, 1506.5,
1352.8, 1256.0, 1149.9, 1043.8 cmꢂ1 1H NMR (CDCl3, 250 MHz)
.
1308.3, 1255.9, 1159.8, 1063.4 cmꢂ1
.
1H NMR (CDCl3, 250 MHz)
d
1.92–2.00 (m, 1H), 2.16–2.35 (m, 2H), 3.42 (dd, J¼9.9, 8.7 Hz, 1H),
d
2.06–2.28 (m, 2H), 2.33 (s, 3H), 2.74–2.85 (m, 1H), 3.77 (br s, 1H),
3.81–4.08 (m, 3H), 4.58 (d, J¼5.1 Hz, 1H), 6.22 (dd, J¼15.8, 8.4 Hz,
1H), 6.62 (dd, J¼8.8, 4.7 Hz, 1H), 6.69 (d, J¼15.8 Hz, 1H), 6.89 (td,
J¼8.5, 2.9 Hz, 1H), 7.13 (dd, J¼9.0, 2.9 Hz, 1H), 7.29–7.48 (m, 5H). 13C
3.81–3.90 (m, 2H), 4.15 (dd, J¼7.8, 3.5 Hz, 1H), 5.12 (d, J¼7.4 Hz, 1H),
6.37 (dd, J¼15.8, 7.9 Hz, 1H), 6.57 (d, J¼8.1 Hz, 1H), 6.68 (d,
J¼15.8 Hz, 1H), 6.98 (dd, J¼8.1, 1.8 Hz, 1H), 7.25 (d, J¼1.8 Hz, 1H),
NMR (CDCl3, 62.9 MHz)
d
29.3, 41.9, 56.8, 65.8, 75.9 (d, J¼1.0 Hz),
7.28–7.49 (m, 5H). 13C NMR (CDCl3, 62.9 MHz)
d
21.0, 26.2, 43.2,
116.2 (d, J¼7.6 Hz),116.4 (d, J¼22.9 Hz),117.3 (d, J¼21.7 Hz),121.9 (d,
J¼6.8 Hz), 126.9, 128.5, 129.2, 129.9, 134.1, 136.7, 141.4 (d, J¼1.8 Hz),
56.5, 67.0, 75.9, 115.5, 122.4, 126.9, 128.2, 128.7, 129.1, 129.8, 130.3,

2092
V. Sridharan et al. / Tetrahedron 65 (2009) 2087–2096
156.5 (d, J¼236.6 Hz). Anal. Calcd for C19H18FNO: C, 77.27; H, 6.14;
and 1,2,3,4-tetrahydro-2-methylquinolines 8 were separated
N, 4.74. Found: C, 76.96; H, 5.99; N, 4.69.
through silica column using petroleum ether/ethyl acetate mixture
(96:4, v/v). When the reaction starting from p-chloroaniline, cin-
namaldehyde, and butyl vinyl ether was performed in ethanol,
a mixture of compounds 7f and 9 was obtained. Data for com-
pounds 7 and 9 follow. Compounds 8 had been previously
described.10
4.2.11. endo-2,3,3a,4,5,9b-Hexahydro-7,9-dimethyl-4-
styrylfuro[3,2-c]quinoline 4f
Viscous liquid. IR (neat) 3360.8, 3025.4, 2869.6, 1614.5, 1586.1,
1468.9, 1356.0, 1299.3, 1164.7, 1037.0 cmꢂ1 1H NMR (CDCl3,
.
250 MHz)
d 2.08–2.23 (m, 2H), 2.28 (s, 3H), 2.46 (s, 3H), 2.76–2.85
(m, 1H), 3.80–3.94 (m, 3H), 4.05 (dd, J¼8.2, 4.0 Hz, 1H), 5.09 (d,
J¼7.1 Hz, 1H), 6.34 (d, J¼1.4 Hz, 1H), 6.39 (dd, J¼15.8, 8.2 Hz, 1H),
6.55 (d, J¼1.4 Hz, 1H), 6.63 (d, J¼15.8 Hz, 1H), 7.27–7.52 (m, 5H). 13C
4.3.1. 4-Ethoxy-1,2,3,4-tetrahydro-2-styrylquinoline 7a
Viscous liquid. IR (neat) 3384.4, 2972.7, 2859.2, 1608.3, 1482.3,
1311.1, 1254.3, 1094.5 cmꢂ1 1H NMR (CDCl3, 250 MHz)
. d 1.33 (t,
NMR (CDCl3, 62.9 MHz)
d
19.7, 21.6, 27.2, 42.8, 56.9, 66.6, 74.1, 113.9,
J¼6.9 Hz, 3H), 1.95–2.08 (m, 1H), 2.38 (ddd, J¼12.5, 5.2, 3.3 Hz, 1H),
3.59–3.80 (m, 2H), 3.93 (br s, 1H), 4.11–4.19 (m, 1H), 4.73 (dd, J¼9.2,
5.2 Hz, 1H), 6.40 (dd, J¼15.8, 7.8 Hz, 1H), 6.56 (d, J¼8.0 Hz, 1H), 6.63
(d, J¼15.8 Hz, 1H), 6.77 (td, J¼8.2, 0.9 Hz, 1H), 7.10 (td, J¼8.2, 1.2 Hz,
117.8, 122.5, 126.9, 128.1, 129.1, 130.2, 131.7, 137.2, 138.7, 140.3, 145.0.
Anal. Calcd for C21H23NO: C, 82.58; H, 7.59; N, 4.59. Found: C, 82.32;
H, 7.42; N, 4.45.
1H), 7.26–7.46 (m, 6H). 13C NMR (CDCl3, 62.9 MHz)
d 16.2, 34.6, 54.1,
4.2.12. exo-2,3,3a,4,5,9b-Hexahydro-7,9-dimethyl-4-styrylfuro-
[3,2-c]quinoline 5f
63.9, 73.7, 114.6, 118.1, 122.7, 126.8, 128.1, 128.2, 128.9, 129.1, 130.8,
132.3, 137.1, 144.2. Anal. Calcd for C19H21NO: C, 81.68; H, 7.58; N,
5.01. Found: C, 81.44; H, 7.49; N, 4.92.
Viscous liquid. IR (neat) 3358.2, 3025.5, 2856.2, 1615.1, 1587.8,
1469.4, 1358.3, 1290.7, 1136.2, 1036.3 cmꢂ1 1H NMR (CDCl3,
.
250 MHz)
d
1.94–2.01 (m, 1H), 2.15–2.25 (m, 2H), 2.27 (s, 3H), 2.43
4.3.2. 1,2,3,4-Tetrahydro-4-propoxy-2-styrylquinoline 7b
(s, 3H), 3.45 (dd, J¼10.0, 8.7 Hz, 1H), 3.81–4.09 (m, 3H), 4.64 (d,
J¼4.3 Hz, 1H), 6.24 (dd, J¼15.8, 8.5 Hz, 1H), 6.36 (d, J¼1.5 Hz, 1H),
6.52 (d, J¼1.5 Hz, 1H), 6.71 (d, J¼15.8 Hz, 1H), 7.33–7.51 (m, 5H). 13C
Viscous liquid. IR (neat) 3378.8, 2960.2, 2874.4, 1608.1, 1493.7,
1311.3, 1255.0, 1093.1 cmꢂ1 1H NMR (CDCl3, 250 MHz)
. d 1.03 (t,
J¼7.5 Hz, 3H), 1.65–1.76 (m, 2H), 1.94–2.06 (m, 1H), 2.39 (ddd,
J¼12.6, 5.3, 3.3 Hz, 1H), 3.48–3.72 (m, 2H), 3.93 (br s, 1H), 4.11–4.19
(m, 1H), 4.71 (dd, J¼9.3, 5.3 Hz, 1H), 6.40 (dd, J¼15.8, 7.8 Hz, 1H),
6.56 (dd, J¼8.0, 1.0 Hz, 1H), 6.63 (d, J¼15.8 Hz, 1H), 6.77 (td, J¼8.2,
1.0 Hz, 1H), 7.10 (td, J¼8.0, 1.0 Hz, 1H), 7.26–7.46 (m, 6H). 13C NMR
NMR (CDCl3, 62.9 MHz) d 19.2, 21.7, 28.9, 42.1, 55.8, 65.2, 74.3, 113.5,
116.2, 121.9, 126.9, 128.4, 129.1, 130.5, 133.9, 136.9, 139.0, 140.3,
145.2. Anal. Calcd for C21H23NO: C, 82.58; H, 7.59; N, 4.59. Found: C,
82.34; H, 7.45; N, 4.51.
(CDCl3, 62.9 MHz)
d 11.3, 23.9, 34.6, 54.1, 70.5, 73.8, 114.6, 118.1,
4.2.13. endo-2,3,3a,4,5,9b-Hexahydro-6,8-dimethyl-4-
styrylfuro[3,2-c]quinoline 4g
122.8, 126.8, 128.1, 128.2, 128.8, 129.1, 130.8, 132.3, 137.1, 144.2. Anal.
Calcd for C20H23NO: C, 81.87; H, 7.90; N, 4.77. Found: C, 81.60; H,
7.88; N, 4.70.
Viscous liquid. IR (neat) 3391.8, 3021.6, 2867.5, 1617.3, 1488.4,
1311.3, 1250.0, 1163.3, 1051.4 cmꢂ1 1H NMR (CDCl3, 250 MHz)
.
d
2.07–2.21 (m, 2H), 2.24 (s, 3H), 2.31 (s, 3H), 2.74–2.84 (m,1H), 3.64
4.3.3. 4-Butoxy-1,2,3,4-tetrahydro-2-styrylquinoline 7c
(br s, 1H), 3.84–3.90 (m, 2H), 4.18 (dd, J¼7.9, 3.6 Hz, 1H), 5.14 (d,
J¼7.4 Hz, 1H), 6.41 (dd, J¼15.8, 8.0 Hz, 1H), 6.71 (d, J¼15.8 Hz, 1H),
6.90 (d, J¼1.5 Hz, 1H), 7.13 (d, J¼1.5 Hz, 1H), 7.29–7.50 (m, 5H). 13C
Viscous liquid. IR (neat) 3387.1, 2956.4, 2859.2, 1608.6, 1481.6,
1310.8, 1254.2, 1093.8 cmꢂ1 1H NMR (CDCl3, 250 MHz)
. d 0.97 (t,
J¼7.2 Hz, 3H), 1.43–1.52 (m, 2H), 1.62–1.71 (m, 2H), 1.93–2.06 (m,
1H), 2.38 (ddd, J¼12.6, 5.2, 3.3 Hz, 1H), 3.51–3.75 (m, 2H), 3.93 (br s,
1H), 4.11–4.19 (m, 1H), 4.70 (dd, J¼9.2, 5.3 Hz, 1H), 6.40 (dd, J¼15.8,
7.8 Hz, 1H), 6.55 (dd, J¼8.0, 1.0 Hz, 1H), 6.63 (d, J¼15.8 Hz, 1H), 6.76
(td, J¼8.0, 1.0 Hz, 1H), 7.09 (td, J¼8.0, 1.0 Hz, 1H), 7.28–7.45 (m, 6H).
NMR (CDCl3, 62.9 MHz) d 17.7, 20.9, 26.1, 43.1, 56.6, 66.9, 76.2, 121.8,
122.4, 126.9, 127.9, 128.3, 128.7, 129.1, 130.4, 131.0, 131.8, 137.1, 140.5.
Anal. Calcd for C21H23NO: C, 82.58; H, 7.59; N, 4.59. Found: C, 82.35;
H, 7.48; N, 4.48.
13C NMR (CDCl3, 62.9 MHz)
d 14.4, 19.9, 32.7, 34.6, 54.1, 68.5, 73.8,
4.2.14. exo-2,3,3a,4,5,9b-Hexahydro-6,8-dimethyl-4-styrylfuro-
[3,2-c]quinoline 5g
114.6, 118.1, 122.8, 126.8, 128.1, 128.2, 128.8, 129.0, 130.8, 132.3, 137.1,
144.2. Anal. Calcd for C21H25NO: C, 82.06; H, 8.11; N, 4.80. Found: C,
81.81; H, 8.00; N, 4.71.
Viscous liquid. IR (neat) 3398.0, 3025.1, 2858.4, 1619.0, 1491.8,
1316.6, 1257.9, 1161.7, 1055.1 cmꢂ1 1H NMR (CDCl3, 250 MHz)
.
d
1.97–2.04 (m, 1H), 2.19 (s, 3H), 2.16–2.26 (m, 2H), 2.32 (s, 3H), 3.49
4.3.4. 6-Chloro-4-ethoxy-1,2,3,4-tetrahydro-2-styrylquinoline 7d
(dd, J¼10.2, 8.7 Hz, 1H), 3.84–3.95 (m, 3H), 4.03–4.12 (m, 1H), 4.64
(d, J¼4.8 Hz, 1H), 6.33 (dd, J¼15.8, 8.6 Hz, 1H), 6.75 (d, J¼15.8 Hz,
1H), 6.94 (d, J¼1.5 Hz, 1H), 7.16 (d, J¼1.5 Hz, 1H), 7.32–7.55 (m, 5H).
Viscous liquid. IR (neat) 3386.9, 2972.4, 2866.9, 1602.9, 1488.0,
1300.8, 1249.1, 1100.1 cmꢂ1 1H NMR (CDCl3, 250 MHz)
. d 1.34 (t,
J¼7.0 Hz, 3H), 1.87–2.00 (m, 1H), 2.37 (ddd, J¼12.6, 5.2, 3.3 Hz, 1H),
3.56–3.84 (m, 2H), 3.94 (br s, 1H), 4.08–4.16 (m, 1H), 4.64 (dd, J¼9.5,
5.2 Hz, 1H), 6.35 (dd, J¼15.8, 8.0 Hz, 1H), 6.46 (d, J¼8.6 Hz, 1H), 6.64
(d, J¼15.8 Hz, 1H), 7.03 (dd, J¼8.5, 2.4 Hz,1H), 7.29–7.45 (m, 6H). 13C
13C NMR (CDCl3, 62.9 MHz)
d 17.7, 20.9, 29.5, 41.9, 56.8, 65.6, 76.6,
120.1, 122.4, 127.0, 127.5, 128.5, 129.2, 129.6, 130.5, 131.4, 133.9,
136.8, 140.8. Anal. Calcd for C21H23NO: C, 82.58; H, 7.59; N, 4.59.
Found: C, 82.29; H, 7.42; N, 4.43.
NMR (CDCl3, 62.9 MHz)
d 16.1, 34.3, 53.9, 64.4, 73.4, 115.7, 122.6,
124.2, 126.9, 127.8, 128.3, 128.7, 129.1, 131.2, 131.7, 136.9, 142.7. Anal.
Calcd for C19H20ClNO: C, 72.72; H, 6.42; N, 4.46. Found: C, 72.45; H,
6.33; N, 4.30.
4.3. General procedure for the CAN-catalyzed synthesis
of 1,2,3,4-tetrahydro-2-styrylquinolines (7)
An equimolar (3 mmol) mixture of the suitable arylamine (1)
and cinnamaldehyde (2) was dissolved in acetonitrile (20 mL) and
stirred at room temperature. To this stirred solution, the suitable
alkyl vinyl ether 6 (4.5 mmol) and 5–15 mol % of CAN were added,
and stirring was continued for the time period specified in Table 2.
After completion of the reaction, as indicated by TLC, the mixture
was extracted with dichloromethane (2ꢁ20 mL), dried (anhydrous
Na2SO4), and evaporated. 1,2,3,4-Tetrahydro-2-styrylquinolines 7
4.3.5. 6-Chloro-1,2,3,4-tetrahydro-4-propoxy-2-styrylquinoline 7e
Viscous liquid. IR (neat) 3401.9, 2960.1, 2873.0, 1602.4, 1488.0,
1300.2, 1250.4, 1098.8 cmꢂ1 1H NMR (CDCl3, 250 MHz)
. d 1.03 (t,
J¼7.4 Hz, 3H), 1.65–1.77 (m, 2H), 1.86–1.99 (m, 1H), 2.38 (ddd,
J¼12.5, 5.2, 3.3 Hz, 1H), 3.47–3.72 (m, 2H), 3.92 (br s, 1H), 4.08–4.17
(m, 1H), 4.63 (dd, J¼9.5, 5.2 Hz, 1H), 6.34 (dd, J¼15.8, 7.9 Hz, 1H),
6.46 (d, J¼8.5 Hz,1H), 6.63 (d, J¼15.8 Hz,1H), 7.02 (dd, J¼8.5, 2.4 Hz,
1H), 7.26–7.45 (m, 6H). 13C NMR (CDCl3, 62.9 MHz)
d 11.3, 23.8, 34.3,

V. Sridharan et al. / Tetrahedron 65 (2009) 2087–2096
2093
54.0, 70.8, 73.6, 115.6, 122.6, 124.3, 126.8, 127.7, 128.2, 128.6, 129.0,
131.3, 131.7, 136.9, 142.7. Anal. Calcd for C20H22ClNO: C, 73.27; H,
6.76; N, 4.27. Found: C, 72.92; H, 6.66; N, 4.27.
132.5, 137.2, 141.9. Anal. Calcd for C20H23NO: C, 81.87; H, 7.90; N,
4.77. Found: C, 81.67; H, 7.82; N, 4.71.
4.3.11. 4-Ethoxy-1,2,3,4-tetrahydro-8-methoxy-2-styrylquinoline 7k
4.3.6. 4-Butoxy-6-chloro-1,2,3,4-tetrahydro-2-styrylquinoline 7f
Viscous liquid. IR (neat) 3419.3, 2970.4, 2865.6, 1588.4, 1493.2,
Viscous liquid. IR (neat) 3386.1, 2956.3, 2862.0, 1601.5, 1488.2,
1324.7, 1249.6, 1082.9 cmꢂ1 1H NMR (CDCl3, 250 MHz)
. d 1.32 (t,
1300.6, 1246.9, 1098.9 cmꢂ1
.
1H NMR (CDCl3, 250 MHz)
d
0.99 (t,
J¼7.0 Hz, 3H), 2.00–2.12 (m, 1H), 2.38 (ddd, J¼12.5, 5.2, 3.2 Hz, 1H),
3.56–3.82 (m, 2H), 3.87 (s, 3H), 4.12–4.21 (m, 1H), 4.42 (br s, 1H),
4.78 (dd, J¼9.1, 5.4 Hz, 1H), 6.46 (dd, J¼15.8, 7.8 Hz, 1H), 6.65 (d,
J¼15.8 Hz, 1H), 6.73–6.78 (m, 2H), 7.04–7.08 (m, 1H), 7.25–7.49 (m,
J¼7.2 Hz, 3H), 1.45–1.54 (m, 2H), 1.64–1.73 (m, 2H), 1.86–1.99 (m,
1H), 2.38 (ddd, J¼12.5, 5.2, 3.3 Hz, 1H), 3.52–3.77 (m, 2H), 3.94 (br s,
1H), 4.08–4.17 (m, 1H), 4.62 (dd, J¼9.5, 5.2 Hz, 1H), 6.35 (dd, J¼15.8,
7.8 Hz, 1H), 6.46 (d, J¼8.5 Hz, 1H), 6.63 (d, J¼15.8 Hz, 1H), 7.04 (dd,
J¼8.5, 2.4 Hz, 1H), 7.29–7.46 (m, 6H). 13C NMR (CDCl3, 62.9 MHz)
5H). 13C NMR (CDCl3, 62.9 MHz)
d 16.2, 34.5, 53.8, 55.9, 63.9, 73.7,
109.0, 116.9, 120.2, 122.6, 126.8, 128.0, 129.0, 130.7, 132.5, 134.2,
137.2, 146.5. Anal. Calcd for C20H23NO2: C, 77.64; H, 7.49; N, 4.53.
Found: C, 77.55; H, 7.33; N, 4.44.
d
14.3, 19.9, 32.7, 34.3, 53.9, 68.9, 73.5, 115.7, 122.6, 124.3, 126.9,
127.8, 128.2, 128.6, 129.1, 131.2, 131.8, 136.9, 142.7. Anal. Calcd for
C21H24ClNO: C, 73.78; H, 7.08; N, 4.10. Found: C, 73.65; H, 7.00; N,
4.01.
4.3.12. 2-(2-Nitrostyryl)-4-ethoxy-1,2,3,4-tetrahydroquinoline 7l
Viscous liquid. IR (KBr) 3336.0, 2963.1, 2861.2, 1608.3, 1519.8,
4.3.7. 4-Ethoxy-6-fluoro-1,2,3,4-tetrahydro-2-styrylquinoline 7g
1485.2, 1304.2, 1255.0, 1082.3, 1032.1 cmꢂ1 1H NMR (CDCl3,
.
Viscous liquid. IR (neat) 3384.2, 2971.4, 2857.0, 1600.2, 1496.5,
250 MHz)
d
1.29 (t, J¼7.0 Hz, 3H), 2.04–2.15 (m,1H), 2.36 (ddd, J¼12.8,
1304.3, 1252.6, 1094.4 cmꢂ1
.
1H NMR (CDCl3, 250 MHz)
d
1.33 (t,
4.7, 4.1 Hz, 1H), 3.59–3.77 (m, 2H), 4.19–4.27 (m, 1H), 4.66 (dd, J¼7.7,
4.9 Hz, 1H), 6.47 (dd, J¼15.6, 8.0 Hz, 1H), 6.57 (dd, J¼8.0, 0.8 Hz, 1H),
6.75 (td, J¼7.5,1.0 Hz,1H), 7.04–7.15 (m, 2H), 7.32–7.44 (m, 2H), 7.54–
J¼7.0 Hz, 3H), 1.87–2.00 (m, 1H), 2.39 (ddd, J¼12.5, 5.3, 3.0 Hz, 1H),
3.58–3.84 (m, 2H), 3.81 (br s, 1H), 4.07–4.15 (m, 1H), 4.68 (dd, J¼9.4,
5.5 Hz, 1H), 6.35 (dd, J¼15.8, 7.8 Hz, 1H), 6.48 (dd, J¼8.8, 4.7 Hz, 1H),
6.64 (d, J¼15.8 Hz, 1H), 6.81 (td, J¼8.7, 3.0 Hz, 1H), 7.13 (ddd, J¼9.5,
2.9, 0.7 Hz, 1H), 7.26–7.45 (m, 5H). 13C NMR (CDCl3, 62.9 MHz)
7.67 (m, 2H), 7.96 (dd, J¼8.1,1.3 Hz).13C NMR (CDCl3, 62.9 MHz)
d 16.1,
34.0, 53.5, 64.1, 73.3,114.8,118.1,122.2,125.0,125.4,128.5,128.8,129.0,
129.1, 133.0, 133.5, 138.2, 143.7, 148.2. Anal. Calcd for C19H20N2O3: C,
70.35; H, 6.21; N, 8.64. Found: C, 70.01; H, 6.09; N, 8.58.
d
13.8, 32.3, 51.9, 61.9, 71.3, 111.9 (d, J¼22.7 Hz), 113.1 (d, J¼7.3 Hz),
113.2 (d, J¼22.9 Hz), 121.9 (d, J¼6.3 Hz), 124.6, 125.9, 126.8, 128.8,
129.6, 134.7, 138.1 (d, J¼1.8 Hz), 154.3 (d, J¼232.7 Hz). Anal. Calcd
for C19H20FNO: C, 76.74; H, 6.78; N, 4.71. Found: C, 76.30; H, 6.70; N,
4.59.
4.3.13. N-[(E)-5-Butoxy-5-ethoxy-1-phenylpent-1-en-3-yl]-4-
chloroaniline 9
Viscous liquid. IR (neat) 3395.9, 3025.5, 2958.7, 2871.7, 1599.7,
1498.2, 1315.9, 1122.0, 1063.8 cmꢂ1 1H NMR (250 MHz, CDCl3)
.
4.3.8. 4-Butoxy-6-fluoro-1,2,3,4-tetrahydro-2-styrylquinoline 7h
d
1.00 (t, J¼7.0 Hz, 3H),1.31 (t, J¼7.1 Hz, 3H),1.43–1.53 (m, 2H),1.60–
Viscous liquid. IR (neat) 3388.3, 2957.6, 2869.1, 1599.6, 1497.1,
1.69 (m, 2H), 2.06–2.11 (m, 2H), 3.47–3.80 (m, 4H), 4.17 (br q,
J¼5.8 Hz, 1H), 4.61 (br s, 1H), 4.76 (t, J¼5.5 Hz, 1H), 6.21 (dd, J¼16.0,
6.0 Hz, 1H), 6.60–6.67 (m, 3H), 7.15 (d, J¼9.0 Hz, 2H), 7.27–7.43 (m,
1304.3, 1252.4, 1098.0 cmꢂ1 1H NMR (CDCl3, 250 MHz)
. d 1.00 (t,
J¼7.2 Hz, 3H), 1.46–1.58 (m, 2H), 1.64–1.75 (m, 2H), 1.86–1.99 (m,
1H), 2.40 (ddd, J¼12.3, 5.1, 3.0 Hz, 1H), 3.52–3.78 (m, 2H), 3.82 (br s,
1H), 4.07–4.16 (m, 1H), 4.67 (dd, J¼9.6, 5.3 Hz, 1H), 6.36 (dd, J¼15.8,
7.8 Hz, 1H), 6.49 (dd, J¼8.7, 4.7 Hz, 1H), 6.64 (d, J¼15.8 Hz, 1H), 6.82
(td, J¼8.4, 2.8 Hz, 1H), 7.15 (dd, J¼9.5, 2.7 Hz, 1H), 7.29–7.46 (m, 5H).
5H). 13C NMR (63 MHz, CDCl3)
d 14.4,15.9,19.9, 32.5, 40.0, 53.4, 62.1,
66.5, 101.7, 114.8, 122.1, 126.8, 128.0, 129.0, 129.4, 130.8, 131.4, 137.1,
146.7. Anal. Calcd for C23H30ClNO2: C, 71.21; H, 7.79; N, 3.61. Found
C, 71.17; H, 7.56; N, 3.86.
13C NMR (CDCl3, 62.9 MHz)
d 14.4, 19.9, 32.7, 34.5, 54.2, 68.7, 73.7,
114.2 (d, J¼22.8 Hz), 115.4 (d, J¼7.6 Hz), 115.5 (d, J¼21.5 Hz), 124.3
(d, J¼6.3 Hz), 126.9, 128.2, 129.1, 131.1, 131.9, 137.0, 140.4 (d,
J¼1.7 Hz),156.4 (d, J¼234.9 Hz). Anal. Calcd for C21H24FNO: C, 77.51;
H, 7.43; N, 4.30. Found: C, 77.22; H, 7.32; N, 4.25.
4.4. General procedure for the DDQ-mediated aromatization
of mixtures of compounds (4) and (5): synthesis of 2-
styrylquinolines (10) and 2,3-dihydro-4-styrylfuro[3,2-c]-
quinolines (11)
4.3.9. 6-Bromo-4-ethoxy-1,2,3,4-tetrahydro-2-styrylquinoline 7i
To a stirred solution of a mixture of endo and exo 2,3,3a,4,5,9b-
hexahydro-4-styrylfuro[3,2-c]quinolines (4 and 5, 1 mmol) in
benzene (15 mL), DDQ (2 mmol) was added slowly and stirring was
continued for 2 h. After completion of the reaction, CH2Cl2 and
water were added, and shaken well with saturated NaHCO3 solu-
tion to get clear layers. Organic layer was separated, aqueous layer
was again extracted with CH2Cl2, the combined organic layer was
dried (anhydrous Na2SO4), and evaporated. The reaction products,
namely 2-styrylquinolines 10 and 2,3-dihydro-4-styrylfuro[3,2-
c]quinolines 11 were separated through silica gel column using
petroleum ether/ethyl acetate mixture (80:20, v/v).
Viscous liquid. IR (neat) 3406.0, 2972.0, 2858.0, 1598.8, 1485.0,
1300.5, 1247.0, 1098.1 cmꢂ1 1H NMR (CDCl3, 250 MHz)
. d 1.34 (t,
J¼7.0 Hz, 3H), 1.91–1.99 (m, 1H), 2.36 (ddd, J¼12.4, 4.8, 3.5 Hz, 1H),
3.58–3.80 (m, 2H), 3.94 (br s, 1H), 4.08–4.16 (m, 1H), 4.63 (dd, J¼9.3,
5.1 Hz, 1H), 6.34 (dd, J¼15.8, 7.8 Hz, 1H), 6.42 (d, J¼8.6 Hz, 1H), 6.62
(d, J¼15.8 Hz, 1H), 7.15 (dd, J¼8.6, 2.2 Hz, 1H), 7.26–7.48 (m, 6H). 13C
NMR (CDCl3, 62.9 MHz)
d 16.0, 34.2, 53.9, 64.4, 73.3, 109.7, 116.1,
124.6, 126.8, 128.2, 129.1, 130.6, 131.3, 131.5, 131.7, 136.9, 143.1. Anal.
Calcd for C19H20BrNO: C, 63.70; H, 5.63; N, 3.91. Found: C, 63.45; H,
5.60; N, 3.88.
4.3.10. 4-Ethoxy-1,2,3,4-tetrahydro-6-methyl-2-styrylquinoline 7j
4.4.1. 2-(2-Styrylquinolin-3-yl)ethanol 10a
Viscous liquid. IR (neat) 3373.6, 2972.5, 2864.9, 1619.2, 1504.8,
IR (KBr) 3299.5, 3026.2, 2920.4, 1595.9, 1493.8, 1417.7, 1321.5,
1301.2, 1251.2, 1095.9 cmꢂ1
.
1H NMR (CDCl3, 250 MHz)
d
1.35 (t,
1211.3, 1066.1 cmꢂ1. 1H NMR (CDCl3, 250 MHz)
d
3.06 (t, J¼6.2 Hz,
J¼7.0 Hz, 3H), 1.95–2.08 (m, 1H), 2.31 (s, 3H), 2.39 (ddd, J¼12.6, 5.3,
3.2 Hz, 1H), 3.58–3.85 (m, 2H), 3.83 (br s, 1H), 4.08–4.16 (m, 1H),
4.71 (dd, J¼9.1, 5.3 Hz, 1H), 6.42 (dd, J¼15.8, 7.8 Hz, 1H), 6.51 (d,
J¼8.1 Hz, 1H), 6.63 (d, J¼15.8 Hz, 1H), 6.93 (dd, J¼8.1, 2.0 Hz, 1H),
2H), 4.01 (t, J¼6.2 Hz, 2H), 4.01 (br s, 1H), 7.28–7.45 (m, 6H), 7.55–
7.62 (m, 3H), 7.70 (s, 1H), 7.85 (d, J¼15.6 Hz, 1H), 7.95 (d, J¼8.4 Hz,
1H). 13C NMR (CDCl3, 62.9 MHz)
d 36.6, 62.6, 124.5, 126.4, 127.4,
127.6,127.9,128.7,129.0,129.2,129.4,130.6,136.5,137.1,137.8,146.9,
154.9. Anal. Calcd for C19H17NO: C, 82.88; H, 6.22; N, 5.09. Found: C,
82.60; H, 6.08; N, 5.00.
7.22–7.45 (m, 6H). 13C NMR (CDCl3, 62.9 MHz)
d 16.2, 21.1, 34.8, 54.2,
64.0, 73.8, 114.9, 122.7, 126.8, 127.4, 128.1, 128.6, 129.1, 129.5, 130.7,

2094
V. Sridharan et al. / Tetrahedron 65 (2009) 2087–2096
4.4.2. 2-(6-Chloro-2-styrylquinolin-3-yl)ethanol 10b
(t, J¼9.0 Hz, 2H), 7.19 (d, J¼16.1 Hz, 1H), 7.34–7.44 (m, 3H), 7.56 (dd,
J¼9.1, 2.4 Hz, 1H), 7.62–7.65 (m, 2H), 7.80 (d, J¼16.1 Hz, 1H), 7.83 (d,
IR (KBr) 3240.3, 3021.5, 2949.5, 1634.4, 1595.7, 1480.3, 1403.2,
1343.8, 1207.7, 1051.0 cmꢂ1. 1H NMR (DMSO-d6, 250 MHz)
d
3.12 (t,
J¼2.4 Hz, 1H), 7.96 (d, J¼9.1 Hz, 1H). 13C NMR (CDCl3, 62.9 MHz)
*
J¼6.6 Hz, 2H), 3.72 (q, J¼6.6 Hz, 2H), 4.92 (t, J¼5.3 Hz,1H), 7.36–7.47
d 29.1, 73.6, 116.8, 116.9, 120.8, 126.2, 127.8, 129.2, 130.8, 130.9, 131.0,
(m, 3H), 7.64–7.78 (m, 4H), 7.90–8.10 (m, 4H). 13C NMR (DMSO-d6,
135.6, 136.9, 147.9, 152.9, 163.4. Anal. Calcd for C19H14ClNO: C, 74.15;
H, 4.58; N, 4.55. Found: C, 74.00; H, 4.47; N, 4.50. *One carbon signal
is merged with others.
62.9 MHz)
d 35.8, 61.6, 124.3, 126.2, 127.9, 128.3, 129.1, 129.2, 129.9,
130.6, 130.9, 132.8, 135.5, 136.3, 136.7, 145.0, 154.9. Anal. Calcd for
C19H16ClNO: C, 73.66; H, 5.21; N, 4.52. Found: C, 73.38; H, 5.08; N,
4.41.
4.4.9. 2,3-Dihydro-8-methyl-4-styrylfuro[3,2-c]quinoline 11c
IR (neat) 3024.7, 2917.6, 1597.9, 1552.9, 1500.5, 1447.6, 1332.2,
4.4.3. 2-(6-Methyl-2-styrylquinolin-3-yl)ethanol 10c
1193.7, 1061.2 cmꢂ1. 1H NMR (CDCl3, 250 MHz)
d 2.51 (s, 3H), 3.50 (t,
IR (KBr) 3231.3, 3021.0, 2947.3, 1636.5, 1598.3, 1494.1, 1347.9,
J¼8.9 Hz, 2H), 4.87 (t, J¼8.9 Hz, 2H), 7.26 (d, J¼16.1 Hz, 1H), 7.33–
7.44 (m, 3H), 7.49 (dd, J¼8.7, 2.0 Hz, 1H), 7.63–7.66 (m, 3H), 7.78 (d,
J¼16.1 Hz, 1H), 7.97 (d, J¼8.7 Hz, 1H). 13C NMR (CDCl3, 62.9 MHz)
1219.5,1051.4 cmꢂ1. 1H NMR (CDCl3, 250 MHz)
d 2.42 (s, 3H), 2.96 (t,
J¼6.0 Hz, 2H), 3.98 (t, J¼6.0 Hz, 2H), 4.66 (br s, 1H), 6.98 (s, 1H),
7.29–7.37 (m, 5H), 7.48–7.56 (m, 3H), 7.73 (d, J¼15.8 Hz, 1H), 7.78 (d,
d
22.0, 29.2, 73.3, 115.9, 116.4, 120.5, 126.9, 127.7, 128.8, 128.9, 129.1,
J¼8.7 Hz, 1H). 13C NMR (CDCl3, 62.9 MHz)
*
d
22.1, 36.7, 62.5, 124.6,
132.4, 134.8, 135.4, 137.2, 148.2, 151.9, 163.6. Anal. Calcd for
C20H17NO: C, 83.59; H, 5.96; N, 4.87. Found: C, 83.32; H, 5.88; N,
4.81.
126.2, 127.5,127.8,128.1,128.9, 129.2, 130.7, 131.5,135.9,137.2,145.2,
153.9. Anal. Calcd for C20H19NO: C, 83.01; H, 6.62; N, 4.84. Found: C,
82.71; H, 6.52; N, 4.77. *Two carbon signals are merged with others.
4.4.10. 8-Bromo-2,3-dihydro-4-styrylfuro[3,2-c]quinoline 11d
4.4.4. 2-(6-Bromo-2-styrylquinolin-3-yl)ethanol 10d
IR (neat) 3026.2, 2911.4, 1616.0, 1587.0, 1492.6, 1328.9, 1276.2,
IR (KBr) 3242.6, 3021.8, 2948.2, 1633.9, 1592.3, 1478.3, 1401.7,
1076.3 cmꢂ1. 1H NMR (CDCl3, 250 MHz)
d
3.46 (t, J¼9.0 Hz, 2H), 4.86
1342.3, 1208.8, 1050.2 cmꢂ1. 1H NMR (DMSO-d6, 250 MHz)
d
3.12 (t,
(t, J¼9.0 Hz, 2H), 7.17 (d, J¼16.0 Hz, 1H), 7.34–7.44 (m, 3H), 7.61–
J¼6.5 Hz, 2H), 3.72 (q, J¼6.5 Hz, 2H), 4.92 (t, J¼5.3 Hz,1H), 7.33–7.47
7.70 (m, 3H), 7.80 (d, J¼16.0 Hz, 1H), 7.88 (d, J¼9.1 Hz, 1H), 8.00 (d,
(m, 3H), 7.63–7.78 (m, 4H), 7.90–7.97 (m, 2H), 8.09–8.12 (m, 2H). 13C
J¼2.1 Hz, 1H). 13C NMR (CDCl3, 62.9 MHz)
*
d 29.1, 73.6, 116.8, 117.5,
NMR (DMSO-d6, 62.9 MHz)
d
35.8, 61.2, 119.2, 124.3, 127.9, 128.9,
119.1,124.2,126.2,127.8,129.2,130.9,133.4,135.7,136.9,148.1,153.0,
163.2. Anal. Calcd for C19H14BrNO: C, 64.79; H, 4.01; N, 3.98. Found:
C, 64.48; H, 3.82; N, 3.90. *One carbon signal is merged with others.
129.1, 129.2, 129.5, 130.9, 132.5, 132.8, 135.6, 136.3, 136.7, 145.2,
155.0. Anal. Calcd for C19H16BrNO: C, 64.42; H, 4.55; N, 3.95. Found:
C, 64.22; H, 4.43; N, 3.80.
4.4.11. 8-Fluoro-2,3-dihydro-4-styrylfuro[3,2-c]quinoline 11e
4.4.5. 2-(6-Fluoro-2-styrylquinolin-3-yl)ethanol 10e
IR (neat) 3024.7, 2919.5, 1604.7, 1509.1, 1401.8, 1333.0, 1227.7,
IR (KBr) 3181.2, 3030.7, 2929.5, 1605.8, 1561.1, 1494.7, 1355.2,
1184.5, 1052.4 cmꢂ1. 1H NMR (CDCl3, 250 MHz)
d
3.53 (t, J¼9.0 Hz,
1223.6, 1138.2, 1062.8 cmꢂ1
.
1H NMR (CDCl3, 250 MHz)
d
3.12 (t,
2H), 4.90 (t, J¼9.0 Hz, 2H), 7.23 (d, J¼16.1 Hz,1H), 7.34–7.50 (m, 5H),
J¼6.3 Hz, 2H), 4.02 (t, J¼6.3 Hz, 2H), 7.12 (dd, J¼8.9, 2.8 Hz, 1H),
7.62–7.67 (m, 2H), 7.80 (d, J¼16.1 Hz, 1H), 8.04 (dd, J¼9.2, 5.2 Hz,
7.35–7.46 (m, 5H), 7.58–7.62 (m, 2H), 7.75 (s, 1H), 7.87 (d, J¼15.8 Hz,
1H). 13C NMR (CDCl3, 62.9 MHz)
d
29.2, 73.5, 105.3 (d, J¼23.0 Hz),
1H), 7.97 (dd, J¼9.3, 5.3 Hz, 1H). 13C NMR (CDCl3, 62.9 MHz)
d
36.4,
116.5, 116.7 (d, J¼10.1 Hz), 120.3 (d, J¼25.8 Hz), 126.4, 127.7, 129.1,
129.2, 131.8 (d, J¼9.0 Hz), 135.3, 136.9, 146.8, 152.1 (d, J¼2.6 Hz),
160.0 (d, J¼246.9 Hz), 163.9 (d, J¼5.4 Hz). Anal. Calcd for
C19H14FNO: C, 78.33; H, 4.84; N, 4.81. Found: C, 78.00; H, 4.72; N,
4.71.
62.6, 110.3 (d, J¼21.8 Hz), 119.7 (d, J¼25.8 Hz), 124.0, 127.9, 128.2 (d,
J¼10.0 Hz), 129.1, 129.2, 131.3, 131.4 (d, J¼9.1 Hz), 136.5, 137.0 (d,
J¼5.3 Hz), 137.1, 144.2, 154.4 (d, J¼2.9 Hz), 160.6 (d, J¼244.7 Hz).
Anal. Calcd for C19H16FNO: C, 77.80; H, 5.50; N, 4.77. Found: C,
77.55; H, 5.38; N, 4.61.
4.4.12. 2,3-Dihydro-7,9-dimethyl-4-styrylfuro[3,2-c]quinoline 11f
4.4.6. 2-(5,7-Dimethyl-2-styrylquinolin-3-yl)ethanol 10f
IR (neat) 3020.1, 2915.7, 1620.0, 1593.7, 1507.4, 1448.1, 1323.0,
IR (KBr) 3354.0, 3021.9, 2933.5, 1596.8, 1493.5, 1447.6, 1370.5,
1274.0,1167.6,1067.7 cmꢂ1. 1H NMR (CDCl3, 250 MHz)
d 2.48 (s, 3H),
1182.5, 1050.3 cmꢂ1
.
1H NMR (DMSO-d6, 250 MHz)
d
2.46 (s, 3H),
2.76 (s, 3H), 3.42 (t, J¼9.1 Hz, 2H), 4.80 (t, J¼9.1 Hz, 2H), 6.98 (s, 1H),
2.59 (s, 3H), 3.14 (t, J¼6.8 Hz, 2H), 3.71 (q, J¼6.8 Hz, 2H), 4.89 (t,
7.22 (d, J¼16.1 Hz, 1H), 7.33–7.41 (m, 3H), 7.63–7.68 (m, 3H), 7.81 (d,
J¼5.4 Hz, 1H), 7.19 (s, 1H), 7.36–7.47 (m, 3H), 7.63–7.79 (m, 4H), 7.92
J¼16.1 Hz, 1H). 13C NMR (CDCl3, 62.9 MHz)
d 20.7, 21.3, 27.1, 71.5,
(d, J¼15.6 Hz,1H), 8.16 (s,1H). 13C NMR (DMSO-d6, 62.9 MHz)
d
18.9,
113.4,114.5,124.9,125.2,126.3,127.5,127.7,127.8,132.8,133.4,135.8,
138.2, 149.9, 150.6, 164.0. Anal. Calcd for C21H19NO: C, 83.69; H,
6.35; N, 4.65. Found: C, 83.44; H, 6.21; N, 4.55.
22.2, 36.6, 62.6, 125.2, 125.5, 126.5, 128.3, 129.4, 129.5, 129.7, 130.8,
134.3, 134.4, 134.9, 137.4, 139.1, 147.7, 154.1. Anal. Calcd for
C21H21NO: C, 83.13; H, 6.98; N, 4.62. Found: C, 82.92; H, 6.86; N,
4.51.
4.5. General procedure for the DDQ-mediated aromatization
of 1,2,3,4-tetrahydro-2-styrylquinolines (7):
synthesis of 2-styrylquinolines (12)
4.4.7. 2,3-Dihydro-4-styrylfuro[3,2-c]quinoline 11a
IR (neat) 3058.3, 2911.4, 1623.6, 1592.0, 1505.7, 1410.5, 1314.3,
1068.1 cmꢂ1. 1H NMR (CDCl3, 250 MHz)
d
3.53 (t, J¼8.9 Hz, 2H), 4.90
(t, J¼8.9 Hz, 2H), 7.28 (d, J¼16.1 Hz, 1H), 7.34–7.46 (m, 4H), 7.63–
7.70 (m, 3H), 7.83 (d, J¼16.1 Hz, 1H), 7.91 (dd, J¼8.3, 1.0 Hz, 1H), 8.07
A solution of the suitable 1,2,3,4-tetrahydro-2-styrylquinoline 7
(1 mmol) in benzene (15 mL) was stirred at room temperature.
DDQ (2 mmol) was added slowly, and stirring was continued for
2 h. After completion of the reaction, CH2Cl2 and water were added,
and shaken well with saturated NaHCO3 solution to get clear layers.
The organic layer was separated, aqueous layer was again extracted
with CH2Cl2, and the combined organic layer was dried (anhydrous
Na2SO4), and evaporated. The crude product was purified
through silica column using petroleum ether/ethyl acetate mixture
(90:10, v/v).
(d, J¼8.6 Hz, 1H). 13C NMR (CDCl3, 62.9 MHz)
d 29.2, 73.5, 115.9,
116.5, 121.8, 125.5, 126.8, 127.7, 129.0, 129.2, 129.3, 130.1, 135.3, 137.1,
149.7, 152.8, 164.2. Anal. Calcd for C19H15NO: C, 83.49; H, 5.53; N,
5.12. Found: C, 83.23; H, 5.38; N, 5.00.
4.4.8. 8-Chloro-2,3-dihydro-4-styrylfuro[3,2-c]quinoline 11b
IR (neat) 3028.2, 2916.9, 1618.5, 1591.3, 1496.2, 1329.6,
1086.8 cmꢂ1. 1H NMR (CDCl3, 250 MHz)
d
3.49 (t, J¼9.0 Hz, 2H), 4.88

V. Sridharan et al. / Tetrahedron 65 (2009) 2087–2096
2095
4.5.1. 2-Styrylquinoline 12a
(s, 3H), 7.35–7.47 (m, 6H), 7.60–7.79 (m, 4H), 8.02 (d, J¼8.5 Hz, 1H).
13C NMR (CDCl3, 62.9 MHz)
18.2, 22.0, 119.7, 124.8, 127.6, 127.8,
128.7, 129.1, 130.0, 132.5, 133.6, 136.0, 136.2, 137.2, 137.3, 146.3,
154.2. Anal. Calcd for C19H17N: C, 87.99; H, 6.61; N, 5.40. Found: C,
87.65; H, 6.54; N, 5.56.
IR (neat) 3056.3, 3030.8, 1611.5, 1595.5, 1503.8, 1445.8, 1316.1,
d
1204.0, 1118.4 cmꢂ1. 1H NMR (CDCl3, 250 MHz)
d
7.32–7.55 (m, 5H),
7.65–7.82 (m, 6H), 8.13 (d, J¼8.4 Hz, 2H). 13C NMR (CDCl3, 62.9 MHz)
d
119.7, 126.6, 127.7, 127.8, 127.9, 129.1, 129.2, 129.4, 129.6, 130.2,
134.8, 136.8, 136.9, 148.7, 156.4. Anal. Calcd for C17H13N: C, 88.28; H,
5.67; N, 6.06. Found: C, 87.95; H, 5.58; N, 6.00.
4.6. General procedure for the CAN-mediated aromatization
of 1,2,3,4-tetrahydro-2-styrylquinolines (7)
4.5.2. 6-Chloro-2-styrylquinoline 12b
IR (neat) 3042.1, 2998.9, 1630.6, 1592.9, 1491.8, 1447.3, 1390.2,
To a stirred solution of the suitable 1,2,3,4-tetrahydro-2-styr-
ylquinoline 7 (1 mmol) in acetonitrile (10 mL) at 0 ꢀC was added
dropwise a solution of CAN (2.5 mmol) in acetonitrile (15 mL).
Stirring was continued for further 30 min at the same temperature,
and water (50 mL) was added. The solution thus obtained was
extracted with CH2Cl2 (3ꢁ20 mL), dried (anhydrous Na2SO4), and
evaporated. The crude products were separated through silica
column using petroleum ether/ethyl acetate mixture (90:10, v/v).
1327.8, 1186.3, 1073.7 cmꢂ1. 1H NMR (CDCl3, 250 MHz)
d
7.33–7.47
(m, 4H), 7.63–7.78 (m, 6H), 8.01–8.06 (m, 2H). 13C NMR (CDCl3,
62.9 MHz) 120.6,126.6,127.7,128.3,128.9,129.2,129.3,131.0,131.2,
d
132.2, 135.3, 135.8, 136.7, 147.0, 156.9. Anal. Calcd for C17H12ClN: C,
76.84; H, 4.55; N, 5.27. Found: C, 76.55; H, 4.40; N, 5.21.
4.5.3. 6-Bromo-2-styrylquinoline 12c
IR (KBr) 3039.7, 2996.6, 1630.1, 1589.0, 1544.6, 1489.6, 1386.5,
1313.3, 1189.2 cmꢂ1. 1H NMR (CDCl3, 250 MHz)
d 7.34–7.46 (m, 4H),
4.6.1. 6-Methyl-8-nitro-2-styrylquinoline 13
7.64–7.80 (m, 5H), 7.93–7.97 (m, 2H), 8.01 (d, J¼8.7 Hz,1H). 13C NMR
IR (neat) 3033.6, 2913.3, 1631.9, 1598.9, 1497.0, 1444.9, 1325.6,
1201.3,1071.3 cmꢂ1. 1H NMR (CDCl3, 250 MHz)
d 2.67 (s, 3H), 7.14 (d,
(CDCl3, 62.9 MHz) d 120.3, 120.6, 127.7, 128.8, 128.9, 129.3, 129.9,
*
131.3, 133.6, 135.4, 135.7, 136.7, 147.2, 156.7. Anal. Calcd for
C17H12BrN: C, 65.83; H, 3.90; N, 4.52. Found: C, 65.71; H, 3.81; N,
4.47. *One carbon signal is merged with others.
J¼16.1 Hz, 1H), 7.22–7.35 (m, 4H), 7.40–7.43 (m, 2H), 7.57
(d, J¼8.5 Hz, 1H), 7.68 (d, J¼2.0 Hz, 1H), 7.92 (d, J¼2.0 Hz, 1H), 8.15
(d, J¼8.5 Hz, 1H). 13C NMR (CDCl3, 62.9 MHz)
d 22.3, 119.8, 126.7,
127.5,128.1,128.5,128.9,129.8,133.7,135.4,135.6,136.1,137.3,138.4,
146.0, 154.4. Anal. Calcd for C18H14N2O2: C, 74.47; H, 4.86; N, 9.65.
Found: C, 74.17; H, 4.80; N, 9.55.
4.5.4. 6-Fluoro-2-styrylquinoline 12d
IR (KBr) 3030.7, 2920.8, 1634.4, 1601.4, 1554.4, 1503.0, 1449.8,
1347.5, 1218.9, 1138.4, 1108.1 cmꢂ1 1H NMR (CDCl3, 250 MHz)
.
d
7.36–7.54 (m, 6H), 7.65–7.73 (m, 4H), 8.07–8.12 (m, 2H). 13C NMR
Acknowledgements
(CDCl3, 62.9 MHz)
d
111.1 (d, J¼21.7 Hz), 120.2 (d, J¼23.6 Hz), 120.5,
127.7, 128.2 (d, J¼9.8 Hz), 129.0, 129.1, 129.2, 132.0 (d, J¼9.1 Hz),
134.8, 136.1 (d, J¼5.2 Hz), 136.8, 145.7, 155.8 (d, J¼2.9 Hz), 160.7 (d,
J¼252.8 Hz). Anal. Calcd for C17H12FN: C, 81.91; H, 4.85; N, 5.62.
Found: C, 81.67; H, 4.76; N, 5.52.
We thank MEC (grant CTQ2006-10930) and UCM-CAM (Grupos
´
de Investigacion, grant 920234) for financial support.
Supplementary data
4.5.5. 6-Methyl-2-styrylquinoline 12e
Supplementary data associated with this article can be found in
the online version, at doi:10.1016/j.tet.2008.12.077.
IR (KBr) 3028.0, 2909.4, 1634.1, 1589.9, 1495.9, 1445.2, 1371.4,
1122.0 cmꢂ1. 1H NMR (CDCl3, 250 MHz)
d 2.56 (s, 3H), 7.34–7.45 (m,
4H), 7.54–7.58 (m, 2H), 7.64–7.71 (m, 4H), 8.01 (d, J¼9.2 Hz, 1H),
References and notes
8.06 (d, J¼8.6 Hz, 1H). 13C NMR (CDCl3, 62.9 MHz)
d 22.0, 119.7,
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126.9, 127.6, 127.8, 128.9, 129.2, 129.3, 129.5, 132.4, 134.3, 136.1,
136.5, 137.0, 147.2, 155.6. Anal. Calcd for C18H15N: C, 88.13; H, 6.16;
N, 5.71. Found: C, 87.96; H, 6.08; N, 5.60.
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4.5.6. 2-(2-Nitrostyryl)quinoline 12f
IR (neat) 3057.7, 1594.3, 1519.6, 1426.9, 1342.7, 1304.6, 1140.0,
1119.5 cmꢂ1
.
1H NMR (CDCl3, 250 MHz)
d
7.41 (d, J¼16.1 Hz, 1H),
7.47–7.57 (m, 2H), 7.63–7.91 (m, 5H), 8.01–8.08 (m, 2H), 8.12–8.19
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119.4, 125.3, 127.1, 127.9,
*
d
128.9, 129.3, 129.6, 129.8, 130.3, 132.7, 133.7, 134.6, 137.0, 148.5,
148.6, 155.6. Anal. Calcd for C17H12N2O2: C, 73.90; H, 4.38; N, 10.14.
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*
with others.
4.5.7. 5,7-Dimethyl-2-styrylquinoline 12g
IR (neat) 3031.8, 2919.9, 1620.1, 1596.0, 1508.7, 1447.8, 1404.8,
1379.6, 1202.6, 1175.0, 1031.9 cmꢂ1 1H NMR (CDCl3, 250 MHz)
.
d
2.54 (s, 3H), 2.64 (s, 3H), 7.18 (s, 1H), 7.34–7.45 (m, 4H), 7.59–7.76
(m, 5H), 8.21 (d, J¼8.7 Hz, 1H). 13C NMR (CDCl3, 62.9 MHz)
d 18.9,
22.3, 118.4, 125.1, 126.9, 127.6, 128.9, 129.2, 129.5, 129.6, 132.9, 134.3,
134.4, 137.0, 139.9, 149.2, 155.8. Anal. Calcd for C19H17N: C, 87.99; H,
6.61; N, 5.40. Found: C, 87.77; H, 6.58; N, 5.32.
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´
7. For some examples, see: (a) Normand-Bayle, M.; Benard, C.; Zouhiri, F.;
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2.52 (s, 3H), 2.88
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