Molecular iodine-catalyzed imino-Diels-Alder reactions: Efficient one-pot synthesis of pyrano[3,2-c]quinolines

Article abstract of DOI:10.1055/s-2005-872676

The successful use of molecular iodine as a catalyst in the intermolecular imino-Diels-Alder reaction is described. A one-pot synthesis of pyrano[3,2-c]quinolines was achieved by three-component coupling of aldehydes and anilines with 2,3-dihydropyran cat

Full text of DOI:10.1055/s-2005-872676

LETTER
2357
Molecular Iodine-Catalyzed Imino-Diels–Alder Reactions: Efficient One-Pot
Synthesis of Pyrano[3,2-c]quinolines
Efficient
One-Pot
S
ynt
i
hesis
o
n
f
Pyrano[3,2-
c
]quin
X
olines ia,* Yue-dong Lu
Department of Applied Chemistry, Zhejiang Sci-Tech University, Hangzhou 310033, P. R. China
Fax +86(571)88802212; E-mail: xiamin@zist.edu.cn
Received 15 July 2005
The use of a convergent three-component reaction from
Abstract: The successful use of molecular iodine as a catalyst in
the intermolecular imino-Diels–Alder reaction is described. A one-
pot synthesis of pyrano[3,2-c]quinolines was achieved by three-
component coupling of aldehydes and anilines with 2,3-dihydropy-
aldehydes, anilines, and alkenes in which the heterocycles
are assembled in a one-pot operation is an efficient meth-
od with particularly valuable application in the combina-
ran catalyzed by iodine. The reactions could be carried out smoothly torial synthesis of tetrahydroquinolines. Unfortunately,
at room temperature within three to six hours to offer the target
for many Lewis acids in a one-pot procedure, the presence
products in good yields. We also investigated solvent effect, sub-
stituent effect, and the amount of iodine required.
of amines and water from the formation of imines can de-
compose or deactivate them. Even if the desired reactions
proceed, more than stoichiometric amounts of the cata-
Key words: Iodine, imino-Diels–Alder, one-pot, three-component,
lysts are needed, since they are trapped by nitrogen.18 Al-
tetrahydroquinolines
though the one-pot operation using lanthanide triflate19 as
the catalyst was reported, its strong acidity and high cost
Tetrahydroquinoline derivatives are a significant class of
natural products and exhibit biological activities in vari-
ous fields,1 such as psychotropic,2 antiallergenic,3 anti-
inflammatory4 and estrogenic activity,5 besides, pyrano-
quinoline derivatives are also used as potent pharmaceuti-
cals.6 It has been established that imino-Diels–Alder
reactions of N-arylimines (the heterodienes) with elec-
tron-rich alkenes are one of the most powerful routes to
build the 1,2,3,4-tetrahydroquinoline scaffold.7 Many
prohibited its use as a versatile reagent in the synthesis of
tetrahydroquinolines.
Recently, molecular iodine has received considerable
attention as an inexpensive and readily available catalyst
for various organic transformations.20 Due to its moderate
Lewis acidity reactions catalyzed by iodine effectively
take place in neutral media under very mild conditions.
Moreover, its water-tolerance and weak ability to accept
electrons make it an excellent candidate for reactions like
the one-pot synthesis of tetrahydroquinolines. To the best
of our knowledge, there is no report on the use of iodine
as a catalyst for this type of reaction. Herein, we describe
our first example of the preparation for pyrano[3,2-
c]quinolines by an iodine-catalyzed three-component
reaction of aldehydes, anilines, and 2,3-dihydropyran in a
one-pot operation.
8
Lewis acids such as InCl3 , Yb(OTf)3,9 Sc(OTf)3,10
BF3·OEt2,11 GdCl3,12 LiClO4,13 LiBF4,14 TFA15 etc were
found to catalyze this reaction. Montmorillonite16 and
fluorinated alcohols17 were also reported to be efficient
for the formation of tetrahydroquinolines. However, all
these methods required a lengthy procedure to prepare the
starting materials. Moreover, most imines are hygroscop-
ic, unstable at high temperature, and difficult to purify by
distillation or column chromatography. Therefore, it is
necessary to develop a simple and effective approach to
tetrahydroquinolines under mild conditions.
A remarkable solvent effect was found to exist in our
iodine-catalyzed one-pot protocol. The selected model
reaction was carried out with benzaldehyde, aniline, and
2,3-dihydropyran in several organic solvents (Scheme 1)
and the results are collected in Table 1.
Scheme 1
SYNLETT 2005, No. 15, pp 2357–2361
1
9
.0
9
.2
0
0
5
Advanced online publication: 07.09.2005
DOI: 10.1055/s-2005-872676; Art ID: U22705ST
© Georg Thieme Verlag Stuttgart · New York

2358
M. Xia, Y.-d. Lu
LETTER
Table 1 Solvent Effect on Iodine-Catalyzed One-Pot Synthesis of
Pyrano[3,2-c]quinolines
According to the above facts, the reactions were extended
to other aldehydes and anilines (Scheme 2) and the results
are shown in Table 3.
Entry
Solvent
EtOH
Yield (%)a
3a/4a Ratiob
1
2
trace
81
–
CH2Cl2
CH3CN
Et2O
23:77
3
84
23:77
4
37
25:75
5
EtOAc
CHCl3
THF
21
29:71
6
–
–
–
–
–
–
7
–
8
Benzene
DMF
trace
–
9
Scheme 2
10
CH3COCH3
trace
a Refers to isolated yields by chromatography.
b Determined by 1H NMR spectroscopy.
It was found that each reaction could be carried out
smoothly by iodine catalysis at room temperature, the
products were obtained as cis/trans isomers without any
other isomer detected. There was no substituent effect by
the aldehydes observed, since aldehydes both with elec-
tron-donating groups and electron-withdrawing groups
could be effectively utilized to generate the required com-
pounds in good yields. Moreover, the reaction time for
every aldehyde was approximately the same. However, an
It was found that both CH3CN and CH2Cl2 were the best
solvents for our reaction while Et2O and EtOAc resulted
in poor yields of the required compounds. Other solvents
afforded either trace or no products. In our later experi-
ments, CH3CN was chosen as the organic solvent to carry
out the iodine-catalyzed reactions. Interestingly, there ap-
peared to be no link between the ratio of the two isomers
formed and the solvent; the trans isomer was always the
major product.
Table 3 One-Pot Synthesis of Pyrano[3,2-c]quinolines Catalyzed
by Iodine from Aldehydes and Anilines in CH3CN.22
Apart from solvents, a range of catalytic amounts of
iodine were also considered. The parallel reactions of
benzaldehyde, aniline, and 2,3-dihydropyran in CH3CN
were carried out in the presence of varying amounts of
iodine and the results are included in Table 2.
R1
R2
Time (h)
Yield (%)a 3/4 Ratiob
a
b
c
d
e
f
H
H
3
84
81
95
91
82
77
58
88
81
83
79
84
84
96
23:77
43:57
8: 92
16:84
24:76
–
H
4-Cl
4-CH3O
4-CH3
2-CH3
3-Cl
3-CF3
H
3
H
3
Table 2 Influence of Iodine on the One-Pot Reaction
H
3
Entry
Amount (mol%)
Yield (%)a
H
4
1
2
3
4
5
5
10
20
30
50
56
68
76
84
88
H
5
g
h
i
H
6
–
4-CH3
4-Br
2-Cl
3-NO2
4-CH3O
4-Cl
3
17:83
17:83
24:76
26:74
9: 91
25:75
3: 97
H
4
j
H
3.5
4
a Isolated yield (chromatography).
k
l
H
H
3
It was observed that the yields improved from 56% to
84% as the catalytic amounts of iodine were increased
from 5 mol% to 30 mol%, respectively. However, when
the amount of iodine was enhanced from 30 mol% to 50
mol%, the yields increased only slightly from 84% to
88%. It was decided that 30 mol% amount of iodine was
sufficient to drive the reaction forward.
m
n
4-Cl
3.5
3
4-CH3O 4-CH3O
a Isolated yield (chromatography).
b Determined by 1H NMR spectroscopy.
Synlett 2005, No. 15, 2357–2361 © Thieme Stuttgart · New York

LETTER
Efficient One-Pot Synthesis of Pyrano[3,2-c]quinolines
2359
(4) Faber, K.; Stueckler, H.; Kapper, T. Heterocycl. Chem.
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1995, 123, 9315x.
apparent substituent effect took place on the anilines.
Compared to those with electron-donating groups,
anilines with electron-withdrawing groups resulted in low
yields and a long reaction time was required.
The reaction of benzaldehyde, 3-chloroaniline, and 2,3-
dihydropyran in our case generated a mixture of four iso-
mers 3f, 3f¢, 4f, and 4f¢, in a ratio of 17:14:55:14, respec-
tively, which was determined by 1H NMR spectroscopy;
the four isomers were formed in a combined yield of 77%.
Unfortunately, the four isomers could not be separated as
pure compounds by column chromatography. In addition,
the reaction of 3-trifluoromethylaniline with benzalde-
hyde and 2,3-dihydropyran also produced a mixture of
three isomers 3g, 4g, and 4g¢ in a ratio of 13:40:47, respec-
tively, in a combined yield of 58%; only 4g¢ could be
isolated as a pure compound (Scheme3).
(7) (a) Katritzky, A. R.; Rachwal, S.; Rachwal, B. Tetrahedron
1996, 52, 15031. (b) Jia, X. D.; Lin, H. C.; Huo, C. D.;
Zhang, W.; Lu, J. M.; Yang, L.; Zhao, G. Y.; Liu, Z. L.
Synlett 2003, 1707. (c) Posson, H.; Hurvois, J. P.; Moinet,
C. Synlett 2000, 209. (d) Zhang, W.; Jia, X.; Yang, L.; Zhao,
G.; Liu, Z. L. Tetrahedron Lett. 2002, 43, 9433.
(8) Bau, G.; Perumal, P. T. Tetrahedron Lett. 1998, 39, 3225.
(9) (a) Makioka, Y.; Shindo, T.; Tanigudi, Y.; Takaki, K.;
Fujwara, Y. Synthesis 1995, 801. (b) Annunziata, R.;
Ciquini, M.; Cozzi, F.; Molteni, V.; Schupp, O. Tetrahedron
1997, 53, 9715. (c) Crousse, B.; Begue, J. P.; Bonnet-
Delpon, D. Tetrahedron Lett. 1998, 39, 5765. (d) Ishitani,
H.; Kobayashi, S. Tetrahedron Lett. 1996, 37, 7357.
(10) (a) Kobayashi, S.; Araki, M.; Ishitani, H.; Nagayama, S.;
Hachiya, I. Synlett 1995, 233. (b) Kobayashi, S.;
Nagayama, S. J. Am. Chem. Soc. 1996, 118, 8977.
(c) Yadav, J. S.; Reddy, B. V. S.; Gayathri, K. U.; Prasad, A.
R. Synthesis 2002, 2537.
(11) Povarov, L. S. Russ. Chem. Rev. 1967, 36, 656.
(12) Ma, Y.; Qian, C. T.; Xie, M. H.; Sun, J. J. Org. Chem. 1999,
64, 6462.
(13) Yadav, J. S.; Subba Reddy, B. V.; Srinivas, R.; Madhuri, C.
H.; Ramalingam, T. Synlett 2001, 240.
(14) Yadav, J. S.; Subba Reddy, B. V.; Madhuri, C. H.; Sabitta,
G. Synthesis 2001, 1065.
(15) (a) Grieco, P. A.; Bahsas, A. Tetrahedron Lett. 1988, 29,
5855. (b) Mellor, J. M.; Merriman, G. D.; Rivere, P.
Tetrahedron Lett. 1991, 32, 7103.
(16) Cabral, J.; Laszlo, P.; Montaufier, M. T. Tetrahedron Lett.
1988, 29, 547.
Scheme 3
(17) Spanedda, M. V.; Hoang, V. D.; Crousse, B.; Bonnet-
Delpon, D.; Begue, J. P. Tetrahedron Lett. 2003, 44, 217.
(18) (a) Boger, D. L.; Weinreb, S. M. Hetero Diels–Alder
Methodology in Organic Synthesis; Academic: San Diego,
1987, Chap. 2. (b) Boger, D. L.; Weinreb, S. M. Hetero
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Eds.; Pergamon: Oxford, 1991, Chap. 5, 401.
(19) Powell, D. A.; Batey, R. A. Tetrahedron Lett. 2003, 44,
7569.
In conclusion, molecular iodine was an effective catalyst
in the one-pot three-component reaction of aldehydes and
anilines with 2,3-dihydropyran, providing pyrano[3,2-
c]quinolines in good yields. In comparison with those re-
ported methods, our approach was superior in terms of
cost, operation, temperature, yields, and reaction time.
Further application of this protocol is now in progress.
(20) (a) Chen, W. Y.; Lu, J. Synlett 2005, 1337. (b) Karimi, B.;
Zareuel, D. Synthesis 2003, 1875. (c) Banik, B. K.;
Samajdar, S.; Banik, I. J. Org. Chem. 2004, 69, 213.
(d) Minakata, S.; Kano, D.; Oderaotoshi, Y.; Komatsu, M.
Angew. Chem. Int. Ed. 2004, 43, 79. (e) Yadav, J. B.; Subba
Reddy, B. V.; Venkateswara, C.; Rao, K. V. J. Chem. Soc.,
Perkin Trans. 1 2002, 1401. (f) Ji, S. J.; Wang, S. Y.; Zhang,
Y.; Chandake, S. L.; Benjamin, S. B. Tetrahedron 2004, 60,
2051.
Acknowledgment
We are grateful for the financial support from the NSFC (project
20402013).
References
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(21) Nagarajan, R.; Magesh, C. J.; Perumal, P. T. Synthesis 2004,
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(22) Pyrano[3,2-c]quinolines 3 and 4; General Procedure.
To a mixture of aldehyde 1 (2 mmol), aniline 2 (2 mmol),
and 2,3-dihydropyran (4 mmol) in CH3CN (10 mL) was
added iodine (0.15 g, 30 mol%) and the solution was stirred
at r.t. for the appropriate time (Table 3). To the reaction
mixture was added 10% aq NaS2O3 soln (20 mL) and the
product was extracted with CH2Cl2 (2 × 10 mL). The
combined organic layers were washed with brine, dried
(Na2SO4), filtered, and the solvent was evaporated. The
(3) Yamada, N.; Kadowaki, S.; Takahashi, K.; Umeza, K.
Biochem. Pharmacol. 1992, 41, 1211.
Synlett 2005, No. 15, 2357–2361 © Thieme Stuttgart · New York

2360
M. Xia, Y.-d. Lu
LETTER
residue was purified by silica gel column chromatography
with petroleum ether (60–90 °C)–EtOAc (95:5) as the eluent
to afford the pure compounds.
J = 8.0 Hz), 7.24 (1 H, s), 7.29–7.42 (5 H, m).
MS: m/z (%) = 279 (M+, 100), 220 (30).
4d: white solid; mp 89–91 °C.
3a: white solid; mp 131–133 °C (Lit.12 130–132 °C).
IR (KBr): 3373, 3055, 3027, 2938, 2856, 1610, 1492, 1365,
1306, 1265, 1071, 913, 749, 702 cm–1.
IR (KBr): 3378, 3045, 2967, 2855, 1613, 1505, 1334, 1267,
1078, 826 cm–1.
1H NMR (400 MHz, CDCl3): d = 1.24–1.27 (1 H, m), 1.30–
1.34 (1 H, m), 1.43–1.50 (1 H, m), 1.61–1.69 (1 H, m), 2.06–
2.09 (1 H, m), 2.23 (3 H, s), 3.69–3.74 (1 H, m), 4.08–4.11
(1 H, m), 4.36 (1 H, d, J = 2.7 Hz), 4.68 (1 H, d, J = 10.8 Hz),
6.45 (1 H, d, J = 8.0 Hz), 6.90 (1 H, dd, J = 8.0, 1.7 Hz), 7.04
(1 H, d, J = 1.0 Hz), 7.31–7.43 (5 H, m).
1H NMR (400MHz, CDCl3): d = 1.27–1.53 (4 H, m), 2.18 (1
H, m), 3.61–3.88 (3 H, m), 4.66 (1 H, d, J = 2.6 Hz), 5.33 (1
H, d, J = 5.6 Hz), 6.58 (1 H, d, J = 7.8 Hz), 6.78 (1 H, t,
J = 7.6 Hz), 7.03 (1 H, t, J = 7.6 Hz), 7.28–7.47 (6 H, m).
MS: m/z (%) = 265 (M+, 77), 206 (100).
4a: yellowish viscous liquid.
MS: m/z (%) = 279 (M+, 100), 221 (82).
IR (neat film): 3378, 3061, 2945, 2857, 1612, 1499, 1366,
3e: white solid; mp 147–148 °C (Lit.12 143–144 °C).
IR (KBr): 3338, 3023, 2933, 2864, 1601, 1474, 1348, 1303,
1270, 1086, 1037, 759, 702 cm–1.
1271, 1072, 913, 756, 708 cm–1.
1H NMR (400 MHz, CDCl3): d = 1.27 (1 H, m), 1.58 (1 H,
m), 1.69 (1 H, m), 1.85 (1 H, m), 2.15 (1 H, m), 3.76 (1 H,
dt, J = 2.5, 11.6 Hz), 4.11 (2 H, m), 4.43 (1 H, d, J = 2.7 Hz),
4.76 (1 H, d, J = 10.8 Hz), 6.59 (1 H, d, J = 7.4 Hz), 6.73 (1
H, t, J = 7.2 Hz), 7.11 (1 H, t, J = 7.2 Hz), 7.27 (1 H, d,
J = 7.4 Hz), 7.39–7.46 (5 H, m).
1H NMR (400 MHz, CDCl3): d = 1.24–1.33 (1 H, m), 1.40–
1.55 (3 H, m), 2.14–2.17 (4 H, m), 3.42 (1 H, m), 3.55–3.59
(1 H, m), 3.69 (1 H, br), 4.70 (1 H, d, J = 2.4 Hz), 5.36 (1 H,
d, J = 5.6 Hz), 6.74 (1 H, t, J = 7.2 Hz), 7.00 (1 H, d, J = 7.2
Hz), 7.32–7.47 (6 H, m).
MS: m/z (%) = 265 (M+, 100), 207 (69).
MS: m/z (%) = 279 (M+, 100), 220 (52).
3b: white solid; mp 171–172 °C (Lit.12170–172 °C).
IR (KBr): 3389, 3078, 3027, 2920, 2855, 1605, 1512, 1321,
1277, 818 cm–1.
4e: white solid; mp 128–129 °C (Lit.12 130–132 °C).
IR (KBr): 3387, 3060, 3027, 2933, 2876, 2827, 1601, 1474,
1364, 1254, 1053, 747, 706 cm–1.
1H NMR (400 MHz, CDCl3): d = 1.26–1.31 (1 H, m), 1.42–
1.51 (3 H, m), 2.03–2.13 (1 H, m), 3.37–3.42 (1 H, m), 3.58–
3.61 (1 H, m), 3.81–3.93 (1 H, br), 4.64 (1 H, d, J = 2.4 Hz),
5.25 (1 H, d, J = 5.6 Hz), 6.51 (1 H, d, J = 8 Hz), 7.02 (1 H,
dd, J = 8.0, 2.4 Hz), 7.28–7.38 (6 H, m).
1H NMR (400MHz, CDCl3): d = 1.30–1.36 (1 H, m), 1.44–
1.50 (1 H, m), 1.62–1.69 (1 H, m), 1.82–1.90 (1 H, m), 2.05
(3 H, s), 2.07–2.11 (1 H, m), 3.72 (1 H, dt, J = 2.4, 11.6 Hz),
4.11 (1 H, dt, J = 11.2, 2.2 Hz), 4.39 (1 H, d, J = 2.6 Hz),
4.75 (1 H, d, J = 11.2 Hz), 6.65 (1 H, t, J = 7.2 Hz), 7.00 (1
H, d, J = 7.2 Hz), 7.12 (1 H, d, J = 7.6 Hz), 7.33–7.46 (5 H,
m).
MS: m/z (%) = 299 (M+, 100), 241 (48).
4b: pale solid; mp 129–131 °C (Lit.12 125–126 °C).
IR (KBr): 3383, 3066, 3027, 2921, 2867, 1607, 151, 1366,
1265, 1079, 824 cm–1.
MS: m/z (%) = 279 (M+, 100), 221 (80).
4g¢: white solid; mp 155–156 °C.
1H NMR (400 MHz, CDCl3): d = 1.33–1.37 (1 H, m), 1.45–
1.49 (1 H, m), 1.60–1.68 (1 H, m), 1.81–1.84 (1 H, m), 2.04–
2.08 (1 H, m), 3.71 (1 H, dt, J = 2.6, 7.6 Hz), 4.06–4.10 (1 H,
m), 4.34 (1 H, d, J = 2.8 Hz), 4.67 (1 H, d, J = 10.8 Hz), 6.46
(1 H, d, J = 8.4 Hz), 7.03 (1 H, dt, J = 8.4, 2.4 Hz), 7.21 (1
H, d, J = 2.4 Hz), 7.32–7.41 (5 H, m).
IR (KBr): 3411, 3035, 2937, 2847, 1597, 1499, 1474, 1433,
1307, 1123, 1053, 918, 796, 735, 702 cm–1.
1H NMR (400 MHz, CDCl3): d = 1.33 (1 H, d, J = 13.2 Hz),
1.49 (1 H, dd, J = 13.8, 2 Hz), 1.66–1.73 (1 H, m), 1.89–1.95
(1 H, m), 2.02 (1 H, d, J = 11.5 Hz), 3.73 (1 H, dt, J = 2.4, 12
Hz), 4.13 (1 H, dd, J = 11.6, 4.8 Hz), 4.69 (1 H, s), 4.86 (1
H, d, J = 11.6 Hz), 6.65 (1 H, d, J = 8.0 Hz), 6.98 (1 H, d,
J = 7.6 Hz), 7.13 (1 H, t, J = 8.0 Hz), 7.32–7.43 (5 H, m).
MS: m/z (%) = 333 (M+, 38), 275 (100).
MS: m/z (%) = 299 (M+, 67), 241 (100).
3c: white solid; mp 146–147 °C (Lit.12 144–146 °C).
IR (KBr): 3340, 3051, 2970, 2860, 1610, 1520, 1365, 1270,
1065, 837, 776 cm–1.
3h: white solid; mp 126–128 °C.
1H NMR (400 MHz, CDCl3): d = 1.25–1.33 (1 H, m), 1.45–
1.55 (3 H, m), 2.12–2.18 (1 H, m), 3.41–3.46 (1 H, m), 3.58
(1 H, m), 3.77 (3 H, s), 4.62 (1 H, d, J = 2.4 Hz), 5.30 (1 H,
d, J = 5.6 Hz), 6.57 (1 H, d, J = 9.2 Hz), 6.71 (1 H, dd,
J = 6.4, 1.8 Hz), 7.03 (1 H, dd, J = 2.9, 0.8 Hz), 7.29–7.43 (5
H, m).
IR (KBr): 3366, 3019, 2941, 2859, 1609, 1477, 1352, 1315,
1213, 1090, 1029, 927, 816, 751 cm–1.
1H NMR (400 MHz, CDCl3): d = 1.29–1.34 (1 H, m), 1.42–
1.55 (3 H, m), 2.13 (1 H, m), 2.36 (3 H, s), 3.43 (1 H, m),
3.56–3.60 (1 H, m), 4.65 (1 H, d, J = 2.4 Hz), 5.31 (1 H, d,
J = 5.6 Hz), 6.58 (1 H, d, J = 8.0 Hz), 6.78 (1 H, t, J = 7.6
Hz), 7.08 (1 H, dt, J = 0.6, 8.0 Hz), 7.18 (2 H, d, J = 8.0 Hz),
7.29 (2 H, d, J = 8.0 Hz), 7.41 (1 H, d, J = 7.6 Hz).
MS: m/z (%) = 279 (M+, 100), 221 (73).
MS: m/z (%) = 295 (M+, 100), 237 (33).
4c: pale solid; mp 97–99 °C (Lit.12 98–100 °C).
IR (KBr):3340, 3021, 2975, 2845, 160, 1495, 1260, 1080,
845 cm–1.
4h: white solid; mp 123–125 °C.
1H NMR (400 MHz, CDCl3): d = 1.31–1.35 (1 H, m), 1.45–
1.48 (1 H, m), 1.62–1.67 (1 H, m), 1.78–1.85 (1 H, m), 2.06–
2.11 (1 H, m), 3.46–3.55 (1 H, br), 3.70 (1 H, dt, J = 2.6, 7.0
Hz), 3.75 (3 H, s), 4.10 (1 H, dt, J = 11.2, 2.2 Hz), 4.36 (1 H,
d, J = 2.8 Hz), 4.65 (1 H, d, J = 10.4 Hz), 6.49 (1 H, d,
J = 8.8 Hz), 6.74 (1 H, dd, J = 8.8, 2.9 Hz), 6.81 (1 H, d,
J = 2.8 Hz), 7.30–7.43 (5 H, m).
IR (KBr): 3370, 3019, 2937, 2855, 1609, 1491, 1372, 1307,
1262, 1078, 812, 743 cm–1.
1H NMR (400 MHz, CDCl3): d = 1.33 (1 H, m), 1.50 (1 H,
m), 1.63 (1 H, m), 1.88 (1 H, m), 2.08 (1 H, m), 2.36 (3 H,
s), 3.70 (1 H, dt, J = 2.5, 11.6 Hz), 4.09 (1 H, dt, J = 10.8, 2.6
Hz), 4.37 (1 H, d, J = 2.7 Hz), 4.67 (1 H, d, J = 10.8 Hz),
6.50 (1 H, d, J = 8.0 Hz), 6.69 (1 H, dt, J = 1.0, 7.2 Hz), 7.06
(1 H, dt, J = 1.6, 8.0 Hz), 7.16–7.23 (3 H, m), 7.30 (2 H, d,
J = 8.0 Hz).
MS: m/z (%) = 295 (M+, 58), 237 (100).
3d: white solid; mp 143–144 °C (Lit.21 142–143 °C).
IR (KBr): 3366, 3023, 2933, 2859, 1617, 1499, 1454, 1352,
1307, 1258, 1082, 808, 698 cm–1.
MS: m/z (%) = 279 (M+, 100), 221 (35).
3i: white solid; mp 168–170 °C.
1H NMR (400 MHz, CDCl3): d = 1.27–1.32 (1 H, m), 1.42–
1.55 (3 H, m), 2.15 (1 H, m), 2.27 (3 H, s), 3.44 (1 H, dt,
J = 2.4, 7.0 Hz), 3.60 (1 H, m), 4.64 (1 H, d, J = 2.2 Hz), 5.30
(1 H, d, J = 5.6 Hz), 6.52 (1 H, d, J = 8.0 Hz), 6.91 (1 H, d,
IR (KBr): 3346, 3051, 2941, 2859, 1605, 1482, 1315, 1262,
1060, 755, 620, 489 cm–1.
1H NMR (400 MHz, CDCl3): d = 1.26–1.33 (1 H, m), 1.44–
1.54 (3 H, m), 2.15 (1 H, m), 3.42 (1 H, m), 3.57–3.61 (1 H,
Synlett 2005, No. 15, 2357–2361 © Thieme Stuttgart · New York

LETTER
m), 4.64 (1 H, d, J = 2.4 Hz), 5.30 (1 H, d, J = 5.5 Hz), 6.60
Efficient One-Pot Synthesis of Pyrano[3,2-c]quinolines
2361
IR (KBr): 3417, 3056, 2966, 2887, 1604, 1534, 1491, 1345,
1277, 1080, 874, 778, 702 cm–1.
(1 H, d, J = 7.4 Hz), 6.80 (1 H, dt, J = 0.8, 7.4 Hz), 7.08 (1
H, t, J = 7.4 Hz), 7.29 (2 H, d, J = 8.4 Hz), 7.42 (1 H, d,
J = 8.0 Hz), 7.50 (2 H, dd, J = 6.8, 1.8 Hz).
MS: m/z (%) = 235 (M + 1, 25), 286 (100).
4i: white solid; mp 131–133 °C.
1H NMR (400 MHz, CDCl3): d = 1.40 (2 H, m), 1.67–1.74
(1 H, m), 1.79–1.86 (1 H, m), 2.12 (1 H, m), 3.74 (1 H, t,
J = 11.2 Hz), 4.11 (1 H, d, J = 9.2 Hz), 4.40 (1 H, d, J = 2.5
Hz), 4.83 (1 H, d, J = 10.8 Hz), 6.57 (1 H, d, J = 8.0 Hz),
6.75 (1 H, t, J = 7.6 Hz), 7.12 (1 H, t, J = 7.6 Hz), 7.24 (1 H,
d, J = 7.6 Hz), 7.55 (1 H, t, J = 8.0 Hz), 7.76 (1 H, d, J = 7.3
Hz), 8.18 (1 H, dd, J = 1.9, 8.0 Hz), 8.31 (1 H, s)
MS: m/z (%) = 310 (M+, 52), 251 (100).
IR (KBr): 3358, 3015, 2937, 2847, 1609, 1495, 1364, 1266,
1078, 1033, 1008, 841, 816, 747, 465 cm–1.
1H NMR (400 MHz, CDCl3): d = 1.32–1.36 (1 H, m), 1.41–
1.47 (1 H, m), 1.62–1.68 (1 H, m), 1.74–1.83 (1 H, m), 2.01–
2.05 (1 H, m), 3.71 (1 H, dt, J = 2.4, 11.6 Hz), 4.09 (1 H, dt,
J = 11.2, 2.1 Hz), 4.37 (1 H, d, J = 2.7 Hz), 4.67 (1 H, d,
J = 10.8 Hz), 6.52 (1 H, d, J = 8.0 Hz), 6.71 (1 H, dt, J = 1.0,
7.6 Hz), 7.09 (1 H, t, J = 7.2 Hz), 7.21 (1 H, dd, J = 1.3, 7.6
Hz), 7.29 (2 H, dd, J = 1.6, 8.4 Hz), 7.48 (2 H, dd, J = 1.7,
8.4 Hz).
4l: white solid; mp 134–135 °C.
IR (KBr): 3387, 3039, 2941, 2892, 2835, 1609, 1495, 1368,
1241, 1057, 767 cm–1.
1H NMR (400 MHz, CDCl3): d = 1.30–1.33 (1 H, m), 1.47–
1.52 (1 H, m), 1.61–1.67 (1 H, m), 1.78–1.85 (1 H, m), 2.06
(1 H, m), 3.71 (1 H, dt, J = 2.4, 11.6 Hz), 4.10 (1 H, dt,
J = 11.2, 2.2 Hz), 4.38 (1 H, d, J = 2.6 Hz), 4.68 (1 H, d,
J = 10.8 Hz), 6.51 (1 H, d, J = 8.0 Hz), 6.70 (1 H, t, J = 7.2
Hz), 6.90 (2 H, d, J = 8.4 Hz), 7.08 (1 H, dt, J = 1.4, 8.0 Hz),
7.21 (1, dd, J = 1.1, 7.6 Hz), 7.34 (2 H, d, J = 8.4 Hz)
MS: m/z (%) = 295 (M+, 100), 236 (182).
MS: m/z (%) = 235 (M + 1, 29), 286 (100).
3j: white solid; mp 165–167 °C.
IR (KBr): 3387, 3072, 3011, 2937, 2847, 1605, 1474, 1315,
1258, 1086, 1029, 743, 702 cm–1.
1H NMR (400 MHz, CDCl3): d = 1.20–1.25 (1 H, m), 1.44–
1.49 (1 H, m), 1.52–1.58 (2 H, m), 2.39–2.42 (1 H, m), 3.42
(1 H, dt, J = 2.3, 11.6 Hz), 3.56–3.61 (1 H, m), 5.06 (1 H, d,
J = 2.1 Hz), 5.33 (1 H, d, J = 5.6 Hz), 6.61 (1 H, d, J = 7.6
Hz), 6.80 (1 H, t, J = 7.6 Hz), 7.09 (1 H, t, J = 7.6 Hz), 7.23–
7.29 (2 H, m), 7.38–7.45 (2 H, m), 7.65 (1 H, dd, J = 1.5, 7.6
Hz).
3m: white solid; mp 187–189 °C.
IR (KBr): 3382, 3068, 2941, 2868, 1601, 1486, 1274, 1082,
841, 808 cm–1.
1H NMR (400 MHz, CDCl3): d = 1.25–1.28 (1 H, m), 1.44–
1.50 (3 H, m), 2.10 (1 H, m), 3.40–3.46 (1 H, m), 3.59–3.63
(1 H, m), 4.63 (1 H, d, J = 2.4 Hz), 5.24 (1 H, d, J = 5.6 Hz),
6.53 (1 H, d, J = 8.6 Hz), 7.03 (1 H, dd, J = 2.2, 8.4 Hz),
7.31–7.36 (4 H, m), 7.38 (1 H, d, J = 1.4 Hz).
MS: m/z (%) = 333 (M+, 53), 274 (100).
MS: m/z (%) = 299 (M+, 70), 241 (100).
4j: colorless viscous liquid.
IR (neat film): 3358, 3056, 3019, 2941, 2855, 1613, 1491,
1364, 1319, 1260, 1082, 755 cm–1.
4m: white solid; mp 154–156 °C.
1H NMR (400 MHz, CDCl3): d = 1.40–1.49 (2 H, m), 1.67–
1.74 (1 H, m), 1.86–1.94 (1 H, m), 2.18–2.22 (1 H, m), 3.6
(1 H, dt, J = 2.8, 11.6 Hz), 3.96–4.00 (1 H, m), 4.43 (1 H, d,
J = 3.1 Hz), 5.17 (1 H, d, J = 9.3 Hz), 6.52 (1 H, d, J = 8.0
Hz), 6.73 (1 H, t, J = 7.4 Hz), 7.20 (1 H, t, J = 8.0 Hz), 7.20–
7.25 (3 H, m), 7.36 (1 H, dd, J = 1.2, 7.6 Hz), 7.48 (1 H, d,
J = 7.6 Hz).
IR (KBr): 3346, 2933, 2847, 1613, 1491, 1268, 1033, 882,
812 cm–1.
1H NMR (400 MHz, CDCl3): d = 1.32–1.38 (1 H, m), 1.43–
1.47 (1 H, m), 1.63–1.69 (1 H, m), 1.75–1.82 (1 H, m), 2.04
(1 H, m), 3.70 (1 H, dt, J = 2.4, 11.6 Hz), 4.07 (1 H, d,
J = 11.6 Hz), 4.34 (1 H, d, J = 2.7 Hz), 4.67 (1 H, d, J = 10.8
Hz), 6.46 (1 H, d, J = 8.4 Hz), 7.04 (1 H, dd, J = 2.4, 8.8 Hz),
7.21 (1 H, d, J = 2.3 Hz), 7.35 (4 H, m).
MS: m/z (%) = 299 (M+, 40), 241 (100).
3k: yellow solid; mp 181–183 °C.
MS: m/z (%) = 333 (M+, 55), 274 (100).
IR (KBr): 3407, 3076, 3011, 2987, 2856, 1601, 1530, 1477,
4n: white solid; mp 151–153 °C.
1266, 1078, 886, 784, 698 cm–1.
IR (KBr): 3346, 3035, 3002, 2970, 2941, 2884, 2839, 1609,
1511, 1462, 1298, 1241, 1172, 1045, 890, 824 cm–1.
1H NMR (400 MHz, CDCl3): d = 1.33–1.38 (1 H, m), 1.45–
1.52 (1 H, m), 1.63 (1 H, m), 1.78–1.84 (1 H, m), 2.05–2.11
(1 H, m), 3.71 (1 H, dt, J = 2.4, 11.2 Hz), 3.75 (3 H, s), 3.83
(3 H, s), 4.36 (1 H, d, J = 2.7 Hz), 4.62 (1 H, d, J = 10.8 Hz),
6.48 (1 H, d, J = 8.8 Hz), 6.72 (1 H, dd, J = 2.8, 8.8 Hz), 6.81
(1 H, d, J = 2.8 Hz), 6.90 (2 H, d, J = 8.4 Hz), 7.34 (2 H, d,
J = 8.4 Hz).
1H NMR (400 MHz, CDCl3): d = 1.20 (1 H, m), 1.44–1.60
(3 H, m), 2.19–2.22 (1 H, m), 3.44 (1 H, dt, J = 2.5, 11.2 Hz),
3.60 (1 H, dt, J = 11.6, 2.0 Hz), 3.83 (1 H, br), 4.80 (1 H, d,
J = 2.3 Hz), 5.34 (1 H, d, J = 5.6 Hz), 6.66 (1 H, d, J = 8.0
Hz), 6.85 (1 H, t, J = 8.0 Hz), 7.13 (1 H, t, J = 7.6 Hz), 7.44
(1 H, d, J = 8.0 Hz), 7.56 (1 H, t, J = 8.0 Hz), 7.76 (1 H, d,
J = 8.0 Hz), 8.17 (1 H, dd, J = 1.5, 8.0 Hz), 8.33 (1 H, s).
MS: m/z (%) = 310 (M+, 53), 251 (100).
4k: yellow solid; mp 159–161 °C.
MS: m/z (%) = 325 (M+, 100), 266 (30).
Synlett 2005, No. 15, 2357–2361 © Thieme Stuttgart · New York