Novel Use of Selectfluor for the Synthesis of cis-Fused Pyrano- and Furanotetrahydroquinolines

Article abstract of DOI:10.1002/adsc.200303101

Aryl imines formed in situ from aryl aldehydes and aromatic amines undergo smooth [4 + 2] cycloaddition reactions with cyclic enol ethers such as 3,4-dihydro-2H-pyran and 2,3-dihydrofuran in the presence of 10 mol % Selectfluor in acetonitrile at room tem

Full text of DOI:10.1002/adsc.200303101

COMMUNICATIONS
TM
Novel Use of Selectfluor for the Synthesis of cis-Fused Pyrano-
and Furanotetrahydroquinolines
J. S. Yadav,* B. V. S. Reddy, V. Sunitha, K. S. Reddy
Division of Organic Chemistry, Indian Institute of ChemicalTechno ol gy, Hyderabad-500 007 India
Fax: ( ‡ 91)-40-27160512, e-mail: yadav@iict.ap.nic.in
Received: May 26, 2003; Accepted: August 15, 2003
and also retains its activity even in the presence of
[
8a]
TM
Abstract: Arylimines formed in situ from aryl
aldehydes and aromatic amines undergo smooth
amines. More recently, Selectfluor has been em-
ployed as an efficient Lewis acid for the one-pot
allylation reactions of imines and for the hydrolysis of
acetals, dithioacetals and tetrahydropyranyl ethers.[
However, there are no precedents of the use of Select-
[
4 ‡ 2] cycloaddition reactions with cyclic enol ethers
8b]
such as 3,4-dihydro-2H-pyran and 2,3-dihydrofuran
in the presence of 10 mol% Se le ctf lu or
TM
in aceto-
TM
nitrile at room temperature to afford pyrano- and
furanotetrahydroquinoline derivatives in excellent
yields with high endo-selectivity.
fluor as promoter for [4 ‡ 2] cycloaddition reactions.
In this report, we wish to describe the synthesis of
tetrahydroquinolines in a one-pot operation using a
TM
substoichiometric amount of Selectfluor under mild
Keywords: arylimines; SelectfluorTM; tetrahydroqui-
nolines
conditions. The treatment of benzaldehyde and aniline
with 2,3-dihydrofuran in the presence of 10 mol% of
TM
Selectfluor in acetonitrile afforded the corresponding
furanoquinolines 2 and 3 in 91% yield (Scheme 1).
In a similar manner, various aromatic imines (formed
in situ from aromatic aldehydes and anilines in acetoni-
The aza-Diels±Alder reaction is becoming a mainstay trile) reacted smoothly with 2,3-dihydrofuran to afford
[
1]
for heterocycles and natural product synthesis. Pyr- the corresponding furano[3,2-c]quinolines in 87 ± 94%
anoquinoline derivatives have been found to possess a yield. In most of the cases, the product was obtained as a
wide spectrum of biological actions such as psychotrop- mixture of 2 endo- and 3 exo-isomers favoring the endo-
[
5b]
ic, anti-allergeric, anti-inflammatory and estrogenic diastereomer.
The diastereomers could be easily
activities.[ Arylimines derived from aromatic amines
2]
separated by column chromatography on silica gel and
can act as heterodienes and undergo imino-Diels±Alder also characterized by NMR spectroscopy. Encouraged
reaction with various dienophiles in the presence of acid by the results obtained with 2,3-dihydrofuran, we turned
[
3±5]
catalysts leading to tetrahydroquinoline derivatives.
our attention to 3,4-dihydro-2H-pyran and various
Generally, more than stoichiometric amounts of the arylimines. Interestingly, a wide range of arylimines
Lewis acids are required because the acids are trapped reacted smoothly with 3,4-dihydro-2H-pyran under
by nitrogen of both reactant and product.[ However, similar reaction conditions to produce pyrano[3,2-c]-
many of these reactions cannot be carried out in a one- quinolines 4 and 5 in excellent yields (Scheme 2).
1]
pot operation with a carbonylcompound, amine and
enolether because the amines and water produced
during imine formation can decompose or deactivate
the Lewis acids. Furthermore, most of the imines are
hygroscopic, unstable at high temperatures and difficult
to purify either by distillation or by column chromatog-
raphy. Subsequently, one-pot procedures have been
Like the five-membered cyclic enol ether (DHF), the
reaction of six-membered 3,4-dihydro-2H-pyran with
developed for this transformation using lanthanide
triflates.[6] In fact, these procedures do not require the
Scheme 1.
isolation of unstable imines prior to the reactions, but
metal triflates are strongly acidic in nature and so thTMe
development of milder alternatives like Selectfluor
would extend the scope of this transformation.
Recently, SelectfluorTM has been introduced commer-
cially as a user-friendly electrophilic fluorinating
[7]
TM
agent. Selectfluor is readily available, easy to handle Scheme 2.
Adv. Synth. Catal. 2003, 345, 1203 ± 1206
DOI: 10.1002/adsc.200303101
¹ 2003 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
1203

COMMUNICATIONS
J. S. Yadav et al.
Table 1. Deprotection of the N-Boc group from aromatic
In conclusion, we describe a simple and efficient
method for the synthesis of cis-fused pyrano- and
furanoquinolines through three-component one-pot
coupling of aldehydes, amines and cyclic enol ethers
amines.[
a]
TM
using Selectfluor as a substoichiometric reagent. The
method offers several advantages including mild reac-
tion conditions, high conversions, greater endo-selectiv-
ity, short reaction times, cleaner reaction profiles, ease of
handling and easy availability of the reagent which make
it attractive and a usefuladdition to the existing
processes for the synthesis of functionalized tetrahy-
droquinolines.
Experimental Section
Melting points were recorded on a Buchi R-535 apparatus and
are uncorrected. IR spectra were recorded on a Perkin-Elmer
1
FT-IR 240-c spectrophotometer using KBr optics. H NMR
spectra were recorded on Gemini-200 spectrometer in CDCl3
using TMS as internalstandard. Mass spectra were recorded on
a Finnigan MAT 1020 mass spectrometer operating at 70 eV.
General Procedure
A mixture of aldehyde (1 mmol), arylamine (1 mmol), 3,4-
dihydro-2H-pyran or 2,3-dihydrofuran (2 mmol) and Select-
TM
fluor (0.1 mmol) in acetonitrile (10 mL) was stirred at 278C
for the appropriate time (Table 1). After completion of the
reaction, as indicated by TLC, the reaction mixture was diluted
with water and extracted with ethylacetate (2 Â 10 mL). The
combined organic extracts were dried and concentrated under
vacuum and the resulting product was purified by column
chromatography on silica gel (Merck, 100 ± 200 mesh, eluted
with a mixture of ethylacetate: n-hexane, 2:8) to afford pure
arylimines also gave the products as a mixture of 4 endo-
and 5 exo-isomers, favoring the endo-diastereomer 4.
1
tetrahydroquinoline. All products were characterized by H,
1
3
C NMR, IR and mass spectroscopy and also by comparison
These three-component coupling reactions proceeded with authentic compounds. The spectroscopic data of products
efficiently at room temperature with high endo-selec- were identicalwith the data reported in the li terature. [
4±6]
cis-4-Phenyl-2,3,3a,4,5,9b-hexahydrofuro[3,2-c]quino-
tivity. In particular, 2,3-dihydrofuran afforded higher
line[ (2a): Solid, m.p. 93 ± 958C; H NMR (CDCl ): d ˆ 1.55
5b]
1
endo-selectivity when compared to 3,4-dihydro-2H-
pyran (Table 1). Among various solvents such as
dichloromethane, tetrahydrofuran and acetonitrile
3
(
m, 1H), 2.25 (m, 1H), 2.75 (m, 1H), 3.80 (m, 3H), 4.70 (d, J ˆ
2
6
6
1
.8 Hz, 1H), 5.25 (d, J ˆ 8.0 Hz, 1H), 6.58 (d, J ˆ 8.0 Hz, 1H),
.80 (t, J ˆ 8.0 Hz, 1H), 7.05 (t, J ˆ 8.0 Hz, 1H), 7.35 ± 7.55 (m,
used for this reaction, CH CN was found to give the
13
3
H); C NMR (CDCl ): d ˆ 24.5, 45.8, 57.3, 66.6, 75.9, 114.9,
3
highest endo-selectivity. However, in the absence of
catalyst, the reactions did not proceed even after long
19.0, 122.5, 126.3, 127.6, 128.2, 128.6, 130.0, 142.3, 144.8;
‡
EIMS: m/z ˆ 251 M , 220, 206, 174, 130, 91; IR (KBr): n
ˆ
max
À1
reaction times (8 ± 12 h). Arylimines show enhanced 3348, 2975, 2855, 1615, 1480, 1039 cm .
TM
reactivity in an acetonitrile solution of Selectfluor
cis-4-(4-Chlorophenyl)-8-methyl-2,3,3a,4,5,9b-hexahydro-
[
4d]
thereby reducing the reaction times, and improving the furo[3,2-c]quinoline
(2b): White solid, m.p. 148 ± 1498C;
1
H NMR (CDCl ): d ˆ 1.50 (m, 1H), 2.20 (m, 1H), 2.35 (s, 3H),
yields and endo-selectivity significantly. As a solvent,
acetonitrile appears to give the best results. This method
is equally effective for both electron-rich as well as
electron-deficient arylimines. The reaction conditions
are mild enough to perform the reactions in the presence
3
2
.64 (m, 1H), 3.60 (brs, NH, 1H), 3.72 (m, 1H), 3.80 (m, 1H),
.60 (d, J ˆ 2.1 Hz, 1H), 5.20 (d, J ˆ 8.0 Hz, 1H), 6.50 (d, J ˆ
.0 Hz, 1H), 6.85 (dd, J ˆ 8.0 and 2.1 Hz, 1H), 7.10 (d, J ˆ
4
8
2
.1 Hz, 1H), 7.35 (d, J ˆ 8.0 Hz, 2H), 7.40 (d, J ˆ 8.0 Hz, 2H);
‡
EIMS: m/z ˆ 299 M , 254, 188, 160, 144, 115, 77; IR (KBr):
TM
of either acid- or base-sensitive aldehydes. Selectfluor
À1
n
ˆ 3345, 2991, 2878, 1610, 1493, 1145, 1041 cm .
max
is a mild Lewis acid, retains its activity even in the
cis-7-Chloro-4-phenyl-2,3,3a,4,5,9b-hexahydrofuro[3,2-
presence of amines and provides a convenient proce- c]quinoline[ (2c): Solid, m.p. 154 ± 1568C; H NMR (CDCl ):
4d]
1
3
dure to perform these reactions.
d ˆ 1.50 (m, 1H), 2.18 (m, 1H), 2.75 (m, 1H), 3.70 ± 3.85 (m,
1204
¹ 2003 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
Adv. Synth. Catal. 2003, 345, 1203 ± 1206

Synthesis of cis-Fused Pyrano- and Furanotetrahydroquinolines
COMMUNICATIONS
3
H), 4.65 (d, J ˆ 2.8 Hz, 1H), 5.20 (d, J ˆ 8.0 Hz, 1H), 6.50 (d,
(CDCl ): d ˆ 1.25 (m, 1H), 1.50 (m, 3H), 2.10 (m, 1H) 3.45 (m,
3
J ˆ 8.2 Hz, 1H), 7.05 (dd, J ˆ 8.2, 3.1 Hz, 1H), 7.25 ± 7.45 (m,
1H), 3.60 (m, 1H), 3.85 (brs, 1H), 4.65 (d, J ˆ 2.7 Hz, 1H), 5.25
(d, J ˆ 5.7 Hz, 1H), 6.50 (d, J ˆ 8.0 Hz, 1H), 7.05 (dd, J ˆ 8.0,
‡
6
3
H); EIMS: m/z ˆ 285 M , 240, 226, 194, 91; IR (KBr): n
ˆ
max
À1
‡2
340, 2965, 2840, 1621, 1500, 1137, 1045 cm .
0.8 Hz, 1H), 7.30 ± 7.40 (m, 6H); EIMS: m/z ˆ 301 M ,298, 240,
cis-4-(4-Fluorophenyl)-2,3,3a,4,5,9b-hexahydrofuro[3,2-
220, 191, 165, 131, 119, 69; IR (KBr): n ˆ 3325, 2965, 2858, 1605,
c]quinoline[ (2d): White solid, m.p. 173 ± 1758C; H NMR
5e]
1
1498, 1247, 1051 cm .
À1
(
CDCl ): d ˆ 1.50 (m, 1H), 2.10 ± 2.15 (m, 1H), 2.60 ± 2.80 (m,
trans-9-Chloro-5-phenyl-3,4,4a,5,6,10b-hexahydro-2H-pyr-
3
ano[3,2-c]quinoline[ (5i): Solid, m.p.124 ± 1268C; H NMR
5b]
1
1
8
7
2
2
H), 3.65 ± 3.80 (m, 3H), 4.64 (d, J ˆ 2.5 Hz, 1H), 5.20 (d, J ˆ
.0 Hz, 1H), 6.50 (d, J ˆ 8.0 Hz, 1H), 6.78 (t, J ˆ 8.0 Hz, 1H),
(CDCl ): d ˆ 1.30 (m, 1H), 1.45 (m, 1H), 1.65 (m, 1H), 1.75 (m,
3
‡
.05 (m, 3H), 7.30 (m, 1H), 7.40 (m, 2H); EIMS: m/z ˆ 269 M ,
1H), 2.05 (m, 1H), 3.65 (dt, J ˆ 11.0, 2.3 Hz, 1H), 4.05 (m, 2H),
4.35 (d, J ˆ 2.7 Hz, 1H), 4.65 (d, J ˆ 10.8 Hz, 1H), 6.45 (d, J ˆ
8.0 Hz ,1H), 7.05 (dd, J ˆ 8.0, 2.0 Hz, 1H), 7.20 (d, J ˆ 2.2 Hz,
40, 224, 198, 174, 130, 117, 77, 39; IR (KBr): n ˆ 3315, 2976,
max
À1
880, 1606, 1508, 1223, 1155, 1049 cm .
cis-4-Phenyl-8-methyl-2,3,3a,4,5,9b-hexahydrofuro[3,2-
0H), 7.25 ± 7.40 (m, 5H); IR (KBr): n ˆ 3325, 2945, 2860,
max
c]quinoline[ (2e): Solid, m.p. 101 ± 1028C; H NMR (CDCl ):
4d]
1
1608, 1495, 1250, 1049 cm .
À1
3
d ˆ 1.45 (m, 1H), 2.15 (m, 1H), 2.30 (s, 3H), 2.75 (m, 1H), 3.60
cis-5-(4-Fluorophenyl)-3,4,4a,5,6,10b-hexahydro-2H-pyra-
[5e]
(
brs, NH, 1H), 3.70 (m, 1H), 3.80 (m, 1H), 4.65 (d, J ˆ 2.8 Hz,
no[3,2-c]quinoline
(4j): White solid, m.p. 174 ± 1758C;
1
1
7
H), 5.30 (d, J ˆ 8.0 Hz, 1H), 6.70 (t, J ˆ 7.8 Hz, 1H), 7.0 (d, J ˆ
H NMR (CDCl ): d ˆ 1.30 (m, 1H), 1.45 ± 1.60 (m, 3H), 2.12
3
.8 Hz, 1H), 7.25 (d, J ˆ 7.8 Hz, 1H), 7.35 ± 7.50 (m, 5H); EIMS:
(m, 1H), 3.40 (dt, J ˆ 11.5 and 2.5 Hz, 1H), 3.56 (dd, J ˆ 11.5
and 2.5 Hz, 1H), 3.75 (brs, 1H, NH), 4.65 (d, J ˆ 2.7 Hz, 1H),
5.28 (d, J ˆ 5.7 Hz, 1H), 6.52 (d, J ˆ 8.0 Hz, 1H), 6.75 (dd, J ˆ
‡
m/z ˆ 265 M , 206, 174, 130, 91; IR (KBr): n ˆ 3348, 2975,
max
À1
2
856, 1615, 1480, 1225, 1045 cm .
cis-4-(4-Methoxyphenyl)-2,3,3a,4,5,9b-hexahydrofuro[3,2-
8.0 and 2.5 Hz, 1H), 7.05 (m, 3H), 7.40 (m, 3H); EIMS: m/z ˆ
[
5e]
‡
c]quinoline
(2f): Pale yellow solid, m.p. 155 ± 1568C,
3
283 M , 239, 225, 198, 150, 148, 91; IR (KBr): n ˆ 3325, 2947,
max
1
À1
H NMR (CDCl ): d ˆ 1.58 (m, 1H), 2.20 (m, 1H), 2.70 (m,
2860, 1608, 1493, 1252, 1045 cm .
1
H), 3.70 ± 3.80 (m, 3H), 3.85 (s, 3H), 4.62 (d, J ˆ 2.2 Hz, 1H),
.22 (d, J ˆ 8.0 Hz, 1H), 6.54 (d, J ˆ 8.0 Hz, 1H), 6.78 (t, J ˆ
.0 Hz, 1H), 6.90 (t, J ˆ 8.0 Hz, 1H), 7.05 (d, J ˆ 8.0 Hz, 2H),
trans-5-(4-Fluorophenyl)-3,4,4a,5,6,10b-hexahydro-2H-
[5e]
5
8
7
1
1
pyrano[3,2-c]quinoline (5j): White solid, m.p. 143 ± 1448C;
1
H NMR (CDCl ): d ˆ 1.30 ± 1.35 (m, 1H), 1.40 ± 1.45 (m, 1H),
3
‡
.40 (m, 3H); EIMS: m/z ˆ 281 M , 252, 236, 224, 167, 155, 141,
1.60 ± 1.70 (m, 1H), 1.75 ± 1.85 (m, 1H), 2.05 (m, 1H), 3.70 (dt,
J ˆ 11.5 and J ˆ 2.5 Hz, 1H), 3.95 (brs, 1H, NH), 4.10 (d, J ˆ
2.5 Hz, 1H), 4.35 (d, J ˆ 2.7 Hz, 1H), 4.70 (d, J ˆ 10.8 Hz, 1H),
6.48 (d, J ˆ 8.0 Hz, 1H), 6.68 (dd, J ˆ 8.0 and 2.5 Hz, 1H), 7.05
21, 91, 69, 43; IR (KBr): n ˆ 3340, 2990, 2870, 1605, 1520,
max
À1
135 cm .
cis-8-Methoxy-4-phenyl-2,3,3a,4,5,9b-hexahydrofuro[3,2-
c]quinoline[ (2g): Pale yellow solid, m.p. 132 ± 1338C, H
5b]
1
(m, 3H), 7.18 (m, 1H), 7.38 (m, 2H); IR (KBr): n ˆ 3327,
max
À1
NMR (CDCl ): d ˆ 1.55 (m, 1H), 2.20 (m, 1H), 2.75 (m, 1H),
2950, 2870, 1610, 1495, 1250, 1049 cm .
3
3
.65 ± 3.85 (m, 3H), 3.78 (s, 3H), 4.62 (d, J ˆ 2.8 Hz, 1H), 5.22 (d,
cis-9-Fluoro-5-phenyl-3,4,4a,5,6,10b-hexahydro-2H-pyra-
no[3,2-c]quinoline[ (4k):; H NMR (CDCl ): d ˆ 1.28 ± 1.40
5e]
1
J ˆ 8.0 Hz, 1H), 6.50 (d, J ˆ 8.6 Hz, 1H), 6.74 (dd, J ˆ 8.6 and
3
2
.8 Hz, 1H), 6.94 (d, J ˆ 2.8 Hz, 1H), 7.25 ± 7.45 (m, 5H);
(m, 1H), 1.40 ± 1.60 (m, 3H), 2.10 ± 2.20 (m, 1H) 3.35 (dt, 1H,
J ˆ 11.7 and 2.6 Hz), 3.55 (dd, 1H, J ˆ 11.7 and 2.6 Hz), 3.65
(brs, 1H, NH), 4.60 (d, J ˆ 2.7 Hz, 1H), 5.20 (d, J ˆ 5.7 Hz, 1H),
6.45 (dd, J ˆ 9.4 and 4.3 Hz, 1H), 6.70 (dt, J ˆ 8.3 and 2.0 Hz,
1H), 7.10 (dd, J ˆ 8.3 and 2.0 Hz, 1H) 7.25 ± 7.45 (m, 5H);
13
C NMR (CDCl ): d ˆ 24.3, 45.8, 55.7, 57.9, 66.7, 76.3, 113.8,
3
115.9, 116.3, 123.5, 126.5, 127.4, 128.6, 139.0, 142.5, 153.0;
‡
EIMS: m/z ˆ 281 M , 236, 206, 160, 141, 115, 91, 41; IR (KBr):
À1
n
ˆ 3305, 2985, 2875, 1611, 1518, 1229, 1049 cm .
max
‡
cis-5-Phenyl-3,4,4a,5,6,10b-hexahydro-2H-pyrano[3,2-
EIMS: m/z ˆ 283 M , 233, 224, 194, 129, 91, 41; IR (KBr):
c]quinoline[ (4h): Solid, m.p. 129 ± 1308C; H NMR (CDCl ):
5b]
1
n
ˆ 3350, 2970, 2860, 1610, 1460, 1051 cm .
À1
3
max
d ˆ 1.25 (m, 1H), 1.50 ± 1.70 (m, 3H), 2.15 ± 2.20 (m, 1H), 3.40
trans-9-Fluoro-5-phenyl-3,4,4a,5,6,10b-hexahydro-2H-pyr-
ano[3,2-c]quinoline[ (5k): Liquid; H NMR (CDCl ): d ˆ
5e]
1
(
3
1
dt, J ˆ 11.3 and 2.4 Hz, 1H), 3.55 (dd, J ˆ 11.3 and 2.4 Hz, 1H),
3
.80 (brs, 1H, NH), 4.70 (d, J ˆ 2.7 Hz, 1H), 5.30 (d, J ˆ 5.6 Hz,
H), 6.55 (d, J ˆ 8.0 Hz, 1H), 6.78 (t, J ˆ 8.0 Hz, 1H), 7.05 (t,
1.30 ± 1.40 (m, 1H), 1.50 ± 1.60 (m, 1H), 1.68 ± 1.70 (m, 1H),
1.80 ± 1.95 (m, 1H), 2.10 ± 2.15 (m, 1H), 3.70 (dt, J ˆ 11.6 and
2.6 Hz, 1H), 3.90 (brs, 1H), 4.10 (dd, J ˆ 11.5 and 2.5 Hz, 1H),
4.30 (d, J ˆ 2.6 Hz, 1H), 4.60 (d, J ˆ 10.7 Hz, 1H), 6.40 (dd, J ˆ
9.4 and 4.3 Hz, 1H), 6.75 (dt, J ˆ 8.3 and 2.0 Hz, 1H), 6.90 (dd,
1
3
J ˆ 7.8 Hz, 1H), 7.25 ± 7.45 (m, 6H); C NMR (CDCl ): d ˆ
3
1
1
1
1
8.2, 25.7, 39.0, 59.3, 60.7, 72.8, 114.4, 118.0, 120.4, 126.9, 127.5,
‡
27.7, 128.0, 128.4, 141.2, 145.2; EIMS: m/z ˆ 265 M , 234, 220,
94, 129, 117, 91, 77; IR (KBr): n ˆ 3340, 2945, 2860, 1610,
J ˆ 8.3 and 2.0 Hz, 1H) 7.25 ± 7.50 (m, 5H); IR (KBr): n
ˆ
max
max
À1
À1
491, 1053 cm .
3350, 2950, 2875, 1608, 1478, 1049 cm .
trans-5-Phenyl-3,4,4a,5,6,10b-hexahydro-2H-pyrano[3,2-
cis-5-(4-Nitrophenyl)-3,4,4a,5,6,10b-hexahydro-2H-pyra-
no[3,2-c]quinoline (4l): Solid; m.p. 189 ± 1908C; H NMR
c]quinoline[ (5h): Pale yellow oil; H NMR (CDCl ): d ˆ
3a]
1
[3a]
1
3
1
3
.25 ± 1.60 (m, 3H), 1.80 ± 1.90 (m, 1H), 2.00 ± 2.10 (m, 1H),
(CDCl ): d ˆ 1.15 ± 1.27 (m, 1H), 1.35 ± 1.60 (m, 3H), 2.10 ± 2.15
3
.75 (dt, J ˆ 11.5 and 2.5 Hz, 1H), 4.00 ± 4.10 (m, 2H), 4.40 (d,
(m, 1H), 3.40 (dt, J ˆ 11.4 and 2.7 Hz, 1H), 3.60 (dd, J ˆ 11.4
and 2.7 Hz, 1H), 3.55 (brs, 1H), 4.80 (d, J ˆ 2.8 Hz, 1H), 5.30 (d,
J ˆ 5.7 Hz, 1H), 6.60 (d, J ˆ 8.0 Hz, 1H), 6.85 (t, J ˆ 7.8 Hz,
1H), 7.10 (t, J ˆ 7.8 Hz, 1H), 7.40 (d, J ˆ 8.0 Hz, 1H), 7.60 (d,
J ˆ 2.5 Hz, 1H), 4.75 (d, J ˆ 10.8 Hz, 1H), 6.50 (d, J ˆ 8.0 Hz,
1
H), 6.70 (t, J ˆ 7.5 Hz, 1H), 7.10 (t, J ˆ 7.5 Hz, 1H), 7.25 (d,
1
3
J ˆ 8.0 Hz, 1H), 7.40 ± 7.55 (m, 5H); C NMR (CDCl ): d ˆ
3
‡
2
1
2
2.3, 24.4, 39.3, 55.0, 69.2, 74.5, 114.2, 117.4, 120.5, 127.7, 127.9,
J ˆ 8.2 Hz, 2H), 8.25 (d, J ˆ 8.2 Hz, 2H); EIMS: m/z ˆ 310 M ,
28.5, 129.4, 130.9, 142.2, 144.5; IR (KBr): n ˆ 3325, 2941,
280, 252, 206, 189, 130, 115, 77; IR (KBr): n ˆ 3347, 2970,
max
max
À1
À1
864, 1607, 1487, 1048 cm .
2845, 1618, 1502, 1047 cm .
cis-9-Chloro-5-phenyl-3,4,4a,5,6,10b-hexahydro-2H-pyra-
trans-5-(4-Nitrophenyl)-3,4,4a,5,6,10b-hexahydro-2H-pyr-
ano[3,2-c]quinoline (5l): Solid; m.p. 169 ± 1708C; H NMR
no[3,2-c]quinoline[ (4i): Solid, m.p. 170 ± 1718C; H NMR
5b]
1
[3a]
1
Adv. Synth. Catal. 2003, 345, 1203 ± 1206
asc.wiley-vch.de
¹ 2003 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
1205

COMMUNICATIONS
J. S. Yadav et al.
(
CDCl ): d ˆ 1.30 ± 1.40 (m, 1H), 1.45 ± 1.50 (m, 1H), 1.60 ± 1.70
J ˆ 2.3 Hz, 1H), 4.50 (d, J ˆ 10.5 Hz, 1H), 6.30 (d, J ˆ 8.0 Hz,
1H), 6.60 (dd, J ˆ 8.0 and 1.8 Hz, 1H), 6.65 (d, J ˆ 1.8 Hz, 1H),
3
(
1
m, 1H), 1.80 ± 1.95 (m, 1H), 2.05 ± 2.15 (m, 1H), 3.70 (t, J ˆ
1.5 Hz, 1H), 4.05 ± 4.15 (m, 2H), 4.40 (d, J ˆ 2.5 Hz, 1H), 4.80
7.10 ± 7.45 (m, 5H); IR (KBr): n ˆ 3353, 2957, 2863, 1621,
max
À1
(
1
d, J ˆ 10.5 Hz, 1H), 6.55 (d, J ˆ 8.0 Hz, 1H), 6.78 (t, J ˆ 7.8 Hz,
1479, 1053 cm .
H), 7.10 (t, J ˆ 7.8 Hz, 1H), 7.20 (d, J ˆ 8.0 Hz, 1H), 7.60 (d,
J ˆ 8.2 Hz, 2H), 8.25 (d, J ˆ 8.2 Hz, 2H); IR (KBr): n ˆ 3350,
max
À1
2
950, 2875, 1623, 1498, 1051 cm .
Acknowledgements
cis-9-Methyl-5-phenyl-3,4,4a,5,6,10b-hexahydro-2H-pyra-
no[3,2-c]quinoline[ (4m): Solid; m.p. 129 ± 1308C; H NMR
3c]
1
BVS, VS and KS thank CSIR, New Delhi, for the award of
fellowships.
(
CDCl ): d ˆ 1.15 ± 1.25 (m, 1H), 1.32 ± 1.60 (m, 3H), 2.05 ± 2.15
3
(
m, 4H), 3.35 (dt, J ˆ 11.4 and 2.7 Hz, 1H), 3.50 (dd, J ˆ 11.4
and 2.7 Hz, 1H), 3.55 (brs, 1H), 4.60 (d, J ˆ 2.7 Hz, 1H), 5.25 (d,
J ˆ 5.6 Hz, 1H), 6.50 (d, J ˆ 8.0 Hz, 1H), 6.85 (d, J ˆ 8.0 Hz,
‡
References and Notes
1
1
1
H), 7.25 ± 7.40 (m, 6H); EIMS: m/z ˆ 279 M , 219, 158, 144,
05, 91; IR (KBr): n ˆ 3345, 2970, 2845, 1610, 1505,
max
À1
[1] a) D. L. Boger, S. M. Weinreb, Hetero-Diels-Alder Meth-
odology in Organic Synthesis, Academic, San Diego, 1987,
Chaps 2 and 9; b) P. Buonora, J. C. Olsen, T. Oh,
Tetrahedron 2001, 57, 6099 ± 6138.
038 cm .
trans-9-Methyl-5-phenyl-3,4,4a,5,6,10b-hexahydro-2H-pyr-
[
3c]
1
ano[3,2-c]quinoline (5m): Oil; H NMR (CDCl ): d ˆ 1.30 ±
3
1
(
3
2
6
.40 (m, 1H), 1.45 ± 1.50 (m, 1H), 1.60 ± 1.70 (m, 1H), 1.80 ± 1.95
[
2] b) N. Yamada, S. Kadowaki, K. Takahashi, K. Umezu,
Biochem. Pharmacol. 1992, 44, 1211 ± 1213; b) K. Faber,
H. Stueckler, T. Kappe, J. Heterocyl. Chem. 1984, 21,
1177 ± 1178; c) J. V. Johnson, S. Rauckman, P. D. Bacca-
nari, B. Roth. J. Med. Chem. 1989, 32, 1942 ± 1949.
m, 1H), 2.05 ± 2.15 (m, 4H), 3.70 (dt, J ˆ 11.5 and 2.4 Hz, 1H),
.90 (brs, 1H), 4.15 (dd, J ˆ 11.5 and 2.4 Hz, 1H), 4.35 (d, J ˆ
.8 Hz, 1H), 4.65(d, J ˆ 10.5 Hz, 1H), 6.40 (d, J ˆ 8.0 Hz, 1H),
.95 (dd, J ˆ 8.0, 1.2 Hz, 1H), 7. 0 (d, J ˆ 1.2 Hz, 1H), 7.30 ± 7.45
(
1
m, 5H); IR (KBr): n ˆ 3350, 2957, 2865, 1611, 1499,
max
À1
041 cm .
[3] a) R. Baudelle, P. Melnyk, B. Deprez, A. Tartar, Tetrahe-
dron 1998, 54, 4125 ± 4140; b) D. F. Worth, S. C. Perricone,
E. F. Elsager, J. Heterocycl. Chem. 1970, 7, 1353 ± 1356;
c) G. Babu, R. Nagarajan, Natarajan, P. T. Perumal,
Synthesis 2000, 661 ± 666.
cis-5-(4-Chlorophenyl)-3,4,4a,5,6,10b-hexahydro-2H-pyra-
no[3,2-c]quinoline[ (4n): Solid, m.p. 169 ± 1708C; H NMR
6d]
1
(
CDCl ): d ˆ 1.23 ± 1.38 (m, 1H), 1.40 ± 1.60 (m, 3H), 2.10 ± 2.20
3
(
m, 1H) 3.45 (dt, J ˆ 11.5 and 2.5 Hz, 1H), 3.60 (dd, J ˆ 11.5 and
2
.5 Hz, 1H), 3.80 (brs, 1H, NH), 4.70 (d, J ˆ 2.8 Hz, 1H), 5.30
[
4] a) L. S. Povarov, Russ. Chem. Rev. 1967, 36, 656 ± 670; b) J.
Cabral, P. Laszlo, Tetrahedron Lett. 1989, 30, 7237 ± 7238;
c) G. Babu, P. T. Perumal, Tetrahedron Lett. 1998, 39,
(
d, J ˆ 5.7 Hz, 1H), 6.60 (d, J ˆ 8.2 Hz, 1H), 6.80 (t, J ˆ 7.8 Hz,
1
2
3
H), 7.10 (t, J ˆ 7.8 Hz, 1H), 7.30 ± 7.45 (m, 5H); EIMS: m/z ˆ
‡
99 M , 268, 240, 229, 188, 156, 130, 115, 77; IR (KBr): n
ˆ
max
3
225 ± 3228; d) J. S. Yadav, B. V. S. Reddy, Ch. Madhuri, G.
À1
354, 2950, 2875, 1630, 1473, 1053 cm .
Sabitha, Synthesis 2001, 1065 ± 1068.
trans-5-(4-Chlorophenyl)-3,4,4a,5,6,10b-hexahydro-2H-
[6dd]
[5] a) B. Crousse, J. P. Begue, D. B. Delpon, Tetrahedron Lett.
1998, 39, 5765 ± 5768; b) Y. Ma, C. Qian, M. Xie, J. Sun, J.
Org. Chem. 1999, 64, 6462 ± 6467; c) M. V. Spanedda, V. D.
Hoang, B. Crousse, D. Bonnet-Delpon, J. P. Begue,
Tetrahedron Lett. 2003, 44, 217 ± 219; e) J. S. Yadav,
B. V. S. Reddy, J. S. S. Reddy, R. S. Rao, Tetrahedron
2003, 59, 1599 ± 1604.
[6] a) Y. Makioka, T. Shindo, Y. Taniguchi, K. Takaki, Y.
Fujwara, Synthesis 1995, 801 ± 804; b) S. Kobayashi, M.
Araki, H. Ishitani, S. Nagayama, I. Hachiya, Synlett 1995,
233 ± 234; c) S. Kobayashi, H. Ishitani, S. Nagayama,
Synthesis 1995, 1195 ± 1202; d) R. Nagarajan, S. Chitra,
P. T. Perumal, Tetrahedron, 2001, 57, 3419 ± 3423.
pyrano[3,2-c]quinoline
(5n): Solid; m.p. 122 ± 1238C;
1
H NMR (CDCl ): d ˆ 1.25 ± 1.50 (m, 2H), 1.60 ± 1.70 (m,
3
1
H), 1.80 ± 190 (m, 1H), 2.0 ± 2.10 (m, 1H), 3.70 (dt, J ˆ 11.5
and 2.5 Hz, 1H), 3.95 (brs, NH, 1H), 4.05 ± 4.10 (m, 1H), 4.35 (d,
J ˆ 2.7 Hz, 1H), 4.70 (d, J ˆ 10.8 Hz, 1H), 6.50 (d, J ˆ 8.2 Hz,
1
H), 6.70 (t, J ˆ 8.0 Hz, 1H), 7.10 (t, J ˆ 8.0 Hz, 1H), 7.20 (d,
J ˆ 8.2 Hz, 1H), 7.30 ± 7.40 (m, 4H); IR (KBr): n ˆ 3351,
max
À1
2
945, 2865, 1628, 1471, 1055 cm .
cis-9-Methoxy-5-phenyl-3,4,4a,5,6,10b-hexahydro-2H-pyr-
[
5b]
1
ano[3,2-c]quinoline (4o): Solid; m.p. 145 ± 1468C; H NMR
(
CDCl ): d ˆ 1.28 ± 1.40 (m, 1H), 1.40 ± 1.60 (m, 3H), 2.10 ± 2.20
3
(
m, 1H) 3.45 (dt, J ˆ 11.8 and 2.7 Hz, 1H), 3.60 (m, 2H), 3.80 (s,
3
H), 4.65 (d, J ˆ 2.7 Hz, 1H), 5.30 (d, J ˆ 5.8 Hz, 1H), 6.50 (d,
J ˆ 8.0 Hz, 1H), 7.0 (d, J ˆ 2.0 Hz, 1H), 7.18 (dd, J ˆ 8.0 and
[
7] a) N. Shibata, E. Suzuki, T. Asahi, M. Shiro, J. Am. Chem.
Soc. 2001, 123, 7001 ± 7009; b) M. D. Burkart, Z. Zhang, S.
‡
2
1
1
.0 Hz, 1H), 7.25 ± 7.50 (m, 5H); EIMS: m/z ˆ 295 M , 237, 225,
60, 142, 117, 91; IR (KBr): n ˆ 3347, 2961, 2868, 1617, 1520,
max
-
C. Hung, C. -H. Wong, J. Am. Chem. Soc. 1997, 119,
1743 ± 11746.
8] a) J. Liu, C.-H. Wong, Tetrahedron Lett. 2002, 43, 3915 ±
À1
476, 1051 cm .
1
trans-9-Methoxy-5-phenyl-3,4,4a,5,6,10b-hexahydro-2H-
[
[5b]
pyrano[3,2-c]quinoline
9
1
(5o): Solid, m.p. 99 ± 1008C (Lit.
3
4
917; b) J. Liu, C.-H. Wong, Tetrahedron Lett. 2002, 43,
037 ± 4039.
1
3 ± 958C); H NMR (CDCl ): d ˆ 1.25 ± 1.50 (m, 3H), 1.60 ±
3
.70 (m, 1H), 1.80 ± 190 (m, 1H), 2.0 ± 2.10 (m, 1H), 3.45 ± 3.70
(
m, 3H), 3.80 (brs, 1H), 4.0 (d, J ˆ 11.0 and 2.3 Hz, 1H), 4.2 (d,
1206
¹ 2003 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
Adv. Synth. Catal. 2003, 345, 1203 ± 1206