LiBF4-Catalyzed Imino-Diels-Alder Reaction: A Facile Synthesis of Pyrano- and Furoquinolines

Article abstract of DOI:10.1055/s-2001-14904

Lithium tetrafluoroborate efficiently catalyzes the imino-Diels-Alder reaction of aldimines with 3,4-dihydro-2H-pyran (DHP) and 2,3-dihydrofuran to afford the corresponding pyrano- and furoquinolines in high yields with high diastereoselectivity.

Full text of DOI:10.1055/s-2001-14904

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1065
LiBF4-Catalyzed Imino-Diels–Alder Reaction: A Facile Synthesis of Pyrano-
and Furoquinolines1
A
Facile
S
h
ynthesis of
P
i
yrano-
l
and Fu
l
roquin
u
olines S. Yadav,* Basi V. Subba Reddy, Chinti Rheddy Madhuri, Gowravaram Sabitha
Organic Chemistry Division I, Indian Institute of Chemical Technology, Hyderabad 500 007, India
Fax +91(040)7170512; E-mail: yadav@iict.ap.nic.in
Received 1 February 2001; revised 12 March 2001
In this report, we describe a novel and highly efficient
Abstract: Lithium tetrafluoroborate efficiently catalyzes the imi-
no-Diels–Alder reaction of aldimines with 3,4-dihydro-2H-pyran
(DHP) and 2,3-dihydrofuran to afford the corresponding pyrano-
and furoquinolines in high yields with high diastereoselectivity.
procedure for the synthesis of the furo(3,2-c)- and pyra-
no(3,2-c)quinolines using a catalytic amount of lithium
tetrafluoroborate in acetonitrile under neutral conditions.
The reaction of benzylideneaniline with 2,3-dihydrofuran
in the presence of catalytic amounts of LiBF4 at room tem-
perature gave the corresponding furo(3,2-c)quinoline in
92% yield (Scheme 1).
Key words: lithium tetrafluoroborate, imino-Diels–Alder reaction,
tetrahydroquinolines
Imino-Diels–Alder reaction is one of the most powerful
synthetic routes for constructing nitrogen-containing six-
membered heterocycles.2 Tetrahydroquinoline deriva-
tives are an important class of compounds in the field of
pharmaceuticals and exhibit a wide spectrum of biological
activities3 including psychotropic, antiallergic, anti-in-
flammatory and estrogenic activity. In addition, pyrano-
quinoline derivatives are found to possess a vast range of
pharmacological activities.4 The imino-Diels–Alder reac-
tion provides an easy access to pyrano- and furoquino-
lines. Imines derived from aromatic amines act as hetero
dienes and undergo imino-Diels–Alder reaction with var-
ious dienophiles. Generally, Lewis acids5–7 are known to
catalyze these reactions. Recently, metal triflates8 were
found to be effective for this transformation. However,
many Lewis acids are deactivated or sometimes decom-
posed by nitrogen-containing reactants. Even when the
desired reactions proceed, more than stoichiometric
amounts of the Lewis acids are required, because the acids
are trapped by nitrogen.2 Furthermore, many imines are
hygroscopic, unstable at high temperatures, and difficult
to purify by distillation or column chromatography.
Therefore, the development of a neutral alternative would
extend the scope of the useful imino-Diels–Alder reac-
tion. Recently, lithium tetrafluoroborate in acetonitrile
(LTAN) has been received as a powerful reaction medium
for effecting various transformations,9 including the hy-
drolysis of acetals, desilylation of ethers, tetrahydropyra-
nylation of alcohols, and glycosidation reactions. Unlike
Scheme 1
Several aldimines (formed in situ from aromatic alde-
hydes and anilines in the presence of Na2SO4 in acetoni-
trile) were treated with 2,3-dihydrofuran to give the
corresponding furoquinolines in 87 93% yield. The reac-
tions proceeded smoothly at ambient temperature under
essentially mild and neutral conditions to give the prod-
ucts in high yields with high diastereoselectivity. The
products were obtained as a mixture of cis and trans iso-
mers, which could be easily separated by column chroma-
tography on silica gel. The product ratio was determined
by 1H NMR spectroscopy of the crude product. Further re-
actions of N-benzylideneanilines with 3,4-dihydro-2H-
pyran (DHP) in the presence of catalytic amounts of lithi-
um tetrafluoroborate resulted in the formation of pyra-
no(3,2-c)quinoline derivatives in 78 90% yield (Scheme
2).
–
ClO4 , the counterion BF4 is non-nucleophilic and non-
oxidizing and hence it provides a convenient procedure to
carry out the reactions under essentially neutral reaction
and workup conditions. These unique catalytic properties
inherent to LiBF4 prompted us to investigate the use of
LiBF4 for the synthesis of tetrahydroquinoline derivatives.
Scheme 2
Synthesis 2001, No. 7, 01 06 2001. Article Identifier:
1437-210X,E;2001,0,07,1065,1068,ftx,en;Z01701SS.pdf.
© Georg Thieme Verlag Stuttgart · New York
ISSN 0039-7881

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as well as neutral reaction and workup conditions. No ad-
ditives or acidic promoters are required and also the reac-
tion conditions are neither acidic nor basic. This method
doesn’t require anhydrous solvents and stringent reaction
conditions. Due to the neutral reaction conditions, this
method is compatible with acid sensitive aldehydes and
unstable imines. The solvent acetonitrile is one of the sol-
vents with best results obtained.
Table LiBF4-catalyzed Synthesis of Pyrano- and Furoquinolines
Entry Imine (1)
Olefin (2) Reaction Yield Product
time (h) (%)a
ratiob
trans:cis
R
R1
H
a
H
1.5
88
85:15
In summary, the present procedure for the synthesis of tet-
rahydroquinoline derivatives is an attractive and alterna-
tive route to the existing ones due to its simplicity, mild
reaction conditions, high yields of products, short reaction
times, greater diastereoseletivity and neutral reaction and
work-up conditions.
b
c
H
H
H
2.0
3.0
92
85
90:10
85:15
4-Cl
d
e
3-Cl
H
H
2.5
3.5
90
87
94:06
75:25
1H NMR spectra were recorded on Varian Gemini 200 at 200 MHz.
2-Me
Synthesis of Compounds 3 and 4; General Procedure
A mixture of aldimine (5 mmol), dihydrofuran or dihydropyran
(7 mmol) and LiBF4 (20% w/w of aldimine) in CH3CN (10 mL) was
stirred at ambient temperature for the appropriate time (Table). Af-
ter completion of the reaction as indicated by TLC, the reaction
mixture was quenched by addition of H2O (15 mL) and extracted
with Et2O (2 20 mL). The combined organic layers were dried
over anhyd Na2SO4, concentrated in vacuo and purified by column
chromatography on silica gel (Merck, 100 200 mesh, EtOAc hex-
ane, 1:9) to afford the pure product.
f
4-Me
H
H
2.0
3.0
93
90
100:0
80:20
g
4-OMe
h
i
3-OMe
H
H
2.5
4.5
89
78
91:09
86:14
3,4-Cl2
3a: solid; mp 129 130 °C.
1
IR (KBr): = 3340, 2970, 2850, 1610, 1490, 1090 cm .
1H NMR (CDCl3): = 1.25 (m, 1H), 1.50 (m, 3H), 2.15 (m, 1H)
3.45 (m, 1H), 3.55 (m, 1H), 3.80 (br s, 1H), 4.70 (d, J = 2.7 Hz, 1H),
5.30 (d, J = 5.6 Hz, 1H), 6.55 (t, J = 8.0 Hz, 1H), 6.75 (t, J = 8.0 Hz,
1H), 7.05 (t, J = 8.0 Hz, 1H), 7.35–7.55 (m, 6H).
j
H
3,4-Cl2
4-Cl
3.0
2.5
87
85
92:08
85:15
k
4-Me
EIMS: m/z (%) = M+ 265 (42), 234 (65), 220 (40), 206 (100), 194
(25), 129 (15), 91 (85), 77 (60).
l
4-Me
H
4-Cl
2.0
2.0
3.0
90
92
84
90:10
90:10
85:15
Anal. Calcd for C18H19NO (265.35): C, 81.48; H, 7.22; N, 5.28.
Found: C, 81.50; H, 7.25; N, 5.30.
m
n
4-Me
4a: viscous liquid.
1H NMR (CDCl3): = 1.25 (m, 1H), 1.50 (m, 1H), 1.65 (m, 1H),
1.85 (m, 1H), 2.15 (m, 1H), 3.75 (dt, J = 11.5 and 2.5 Hz, 1H), 3.95
(m, 2H), 4.40 (d, J = 2.9 Hz, 1H), 4.75 (d, J = 10.7 Hz, 1H), 6.50 (d,
J = 8.1 Hz, 1H), 6.70 (t, J = 8.1 Hz, 1H), 7.10 (t, J = 8.1 Hz, 1H),
7.25 (d, J = 8.1 Hz, 1H), 7.35–7.55 (m, 5H).
H
4-OCH3
o
H
4-OCH3
2.5
91
93:07
3b: solid; mp 93 95 °C.
IR (KBr): = 3315, 2975, 2855, 1615, 1480, 1070 cm .
1
a Isolated and unoptimized yields after column chromatography.
b Product ratio was determined from the 1H NMR spectrum of the
crude product.
1H NMR (CDCl3): = 1.55 (m, 1H), 2.25 (m, 1H), 2.75 (m, 1H)
3.80 (m, 3H), 4.70 (d, J = 2.8 Hz, 1H), 5.25 (d, J = 8.0 Hz, 1H), 6.58
(d, J = 8.0 Hz, 1H), 6.80 (t, J = 8.0 Hz, 1H), 7.05 (t, J = 8.0 Hz, 1H),
7.35–7.55 (m, 6H).
EIMS: m/z (%) = M+ 251 (100), 220 (25), 206 (85), 174 (25), 130
(40), 91 (45).
In all the cases the products were obtained as a mixture of
cis and trans isomers, which were separated by column
chromatography. All the products were characterized
1
from IR, H, 13C NMR and mass spectra. Several exam- Anal. Calcd for C17H17NO (251.33): C, 81.24; H, 6.82; N, 5.57.
Found: C, 81.26; H, 6.83; N, 5.58.
ples illustrating this novel and rapid procedure for the syn-
thesis of tetrahydroquinolines are summarized in the
Table. There are several advantages in the use of lithium
tetrafluoroborate for this transformation, which include
mild reaction conditions, improved yields, enhanced
rates, greater diastereoselectivity, experimental simplicity
4b: colorless liquid.
1H NMR (CDCl3): = 1.70 (m, 1H), 2.05 (m, 1H), 2.45 (m, 1H),
3.80 (m, 3H), 4.05 (m, 1H), 4.60 (d, J = 5.0 Hz, 1H), 6.65 (d, J = 8.0
Hz, 1H), 6.80 (t, J = 8.0 Hz, 1H), 7.15 (t, J = 8.0 Hz, 1H), 7.25–7.45
(m, 6H).
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A Facile Synthesis of Pyrano- and Furoquinolines
1067
3c: solid; mp 170 171 °C.
2.8 Hz, 1H), 5.30 (d, J = 8.0 Hz, 1H), 6.70 (t, J = 7.8 Hz, 1H), 7.0
(d, J = 7.8 Hz, 1H), 7.25 (d, J = 7.8 Hz, 1H), 7.35–7.50 (m, 5H).
IR (KBr): = 3345, 2965, 2855, 1615, 1485, 1075 cm–1.
1H NMR (CDCl3): = 1.25 (m, 1H), 1.50 (m, 3H), 2.10 (m, 1H)
3.45 (m, 1H), 3.60(m, 1H), 3.85 (br s, 1H), 4.65 (d, J = 2.7 Hz, 1H),
5.25 (d, J = 5.7 Hz, 1H), 6.50 (d, J = 8.0 Hz, 1H), 7.05 (dd, J = 8.0
and 0.8 Hz, 1H), 7.30–7.40 (m, 6H).
EIMS: m/z (%) = M+ 265 (75), 206 (100), 174 (35), 130 (60), 91
(85).
Anal. Calcd for C18H19NO (265.35): C, 81.48; H, 7.72; N, 5.28.
Found: C, 81.49; H, 7.76; N, 5.31.
EIMS: m/z (%) = [M + 2] 301 (19), 298 (98), 240 (100), 220 (25),
191 (40), 165 (75), 131 (60), 119 (35), 69 (40).
4f: solid; mp 90–92 °C.
IR (KBr): = 3345, 2960, 2855, 1615, 1509, 1065 cm–1.
Anal. Calcd for C18H18NClO (299.79): C, 72.11; H, 6.05; N, 4.67;
Cl, 11.83. Found: C, 72.15; H, 6.10; N, 4.68; Cl, 11.89.
1H NMR (CDCl3): = 1.65 (m, 1H), 2.05 (m, 1H), 2.35 (s, 3H), 2.45
(m, 1H), 3.80 (m, 2H), 4.05 (m, 2H), 4.60 (d, J = 5.0 Hz, 1H), 6.70
(t, J = 7.8 Hz, 1H), 6.95 (d, J = 7.8 Hz, 1H), 7.25–7.45 (m, 6H).
4c: solid; mp 124 126 °C.
IR (KBr): = 3340, 2975, 2845, 1605, 1495, 1080 cm–1.
3g: solid; mp 145 146 °C.
1H NMR (CDCl3): = 1.30 (m, 1H), 1.45 (m, 1H), 1.65 (m,
1H),1.75 (m, 1H), 2.05 (m, 1H), 3.65 (dt, J = 15.0 and 3.0 Hz, 1H),
4.05 (m, 2H), 4.35 (d, J =2.7 Hz, 1H), 4.65 (d, J = 10.8 Hz, 1H), 6.45
(d, J = 8.0 Hz ,1H), 7.05 (dd, J = 8.0 and 2.0 Hz, 1H), 7.20 (d, J =
2.2 Hz), 7.25–7.40 (m, 5H).
IR (KBr): = 3340, 2970, 2860, 1610, 1520, 1065 cm–1.
1H NMR (CDCl3): = 1.30 1.50 (m, 4H), 2.15 (m, 1H), 3.40 (m,
1H), 3.55 (m, 1H), 3.80 (s, 3H), 4.65 (d, J = 2.0 Hz, 1H), 5.25 (d, J
= 5.2 Hz, 1H), 6.65 (d, J = 8.2 Hz, 1H), 6.88 (dd, J = 8.2 and 2.7 Hz,
1H), 7.05 (d, J = 2.7 Hz, 1H), 7.25 7.40 (m, 5H).
3d: solid; mp154 156 °C.
IR (KBr): = 3340, 2965, 2840, 1620, 1500, 1070 cm .
1H NMR (CDCl3): = 1.50 (m, 1H), 2.18 (m, 1H), 2.75 (m, 1H),
3.70–3.85 (m, 3H), 4.65 (d, J = 2.8 Hz, 1H), 5.20 (d, J = 8.0 Hz, 1H),
6.50 (d, J = 8.2 Hz, 1H), 7.05 (dd, J = 8.2 and 3.1 Hz, 1H), 7.25–
7.45 (m, 6H).
EIMS: m/z = M+ 295 (100), 237 (60), 225 (40), 160 (80), 91 (55).
1
Anal. Calcd for C19H21NO2 (295.38): C, 77.26; H, 7.17; N, 4.74.
Found: C, 77.28; H, 7.20; N, 4.77.
4g: solid; mp 97 99 °C.
IR (KBr): = 3325, 2965, 2865, 1605, 1515, 1070 cm–1.
EIMS: m/z (%) = M+ 285 (73), 240 (100), 226 (85), 194 (25), 91
(50).
1H NMR (CDCl3): = 1.25 (m, 1H), 1.40 (m, 1H), 1.60 (m, 1H),
1.75 (m, 1H), 2.05 (m, 1H), 3.65 (m, 1H), 3.75 (s, 3H), 4.05 (m,
1H), 4.35 (d, J = 2.7 Hz, 1H), 4.60 (d, J = 10.5 Hz, 1H), 6.55 (d, J
= 8.1 Hz, 1H), 6.60 (dd, J = 8.1 and 2.7 Hz, 1H), 6.80 (d, J = 2.7 Hz,
1H), 7.25–7.35 (m, 5H).
Anal. Calcd for C17H16NClO (285.77): C, 71.45; H, 5.64; N, 4.90;
Cl, 12.41. Found: C, 71.47; H, 5.65; N, 4.95; Cl, 12.45.
4d: solid; mp 98 99 °C.
IR (KBr): = 3345, 2960, 2845, 1615, 1505, 1075 cm–1.
3h: solid; mp 131 132 °C.
IR (KBr): = 3340, 2975, 2870, 1615, 1525, 1075 cm–1.
1H NMR (CDCl3): = 1.70 (m, 1H), 2.05 (m, 1H), 2.45 (m, 1H),
3.80 (m, 2H), 3.90–4.15 (m, 2H), 4.50 (d, J = 5.0 Hz, 1H), 6.50 (d,
J = 8.1 Hz, 1H), 7.05 (dd, J = 8.1 and 2.8 Hz, 1H), 7.25–7.40 (m,
6H).
1H NMR (CDCl3): = 1.55 (m, 1H), 2.20 (m, 1H), 2.70 (m, 1H),
3.60–3.75 (m, 3H), 3.85 (s, 3H), 4.65 (d, J = 2.6 Hz, 1H), 5.25 (d, J
= 8.0 Hz, 1H), 6.55 (d, J = 8.0 Hz , 1H), 6.75 (dd, J = 8.0 and 2.6
Hz, 1H), 7.05 (d, J = 2.6 Hz, 1H), 7.30–7.45 (m, 5H).
3e: solid; mp 142 143 °C.
EIMS: m/z (%) = M+ 281 (13), 250 (35), 222 (100), 174 (15), 130
(55), 115 (25), 91 (75).
IR (KBr): = 3345, 2970, 2845, 1610, 1509, 1030 cm–1.
1H NMR (CDCl3): = 1.40 1.60 (m, 4H), 2.10 (m, 1H), 2.35 (s,
3H), 3.40 (m, 1H), 3.55–3.70 (m, 2H), 4.65 (d, J = 2.5 Hz, 1H), 5.25
(d, J = 5.2 Hz, 1H), 6.70 (t, J = 7.8 Hz, 1H), 7.05 (dd, J = 7.8 and
0.7 Hz, 1H), 7.35–7.45 (m, 6H).
Anal. Calcd for C18H19NO2 (281.35): C, 76.84; H, 6.81; N, 4.98.
Found: C, 76.87; H, 6.86; N, 4.99.
4h: solid; mp 95 96 °C.
EIMS: m/z (%) = M+ 279 (40), 219 (100), 158 (35), 144 (60), 105
IR (KBr): = 3345, 2970, 2875, 1610, 1520, 1065 cm–1.
(75), 91 (45).
1H NMR (CDCl3): = 1.25 (m, 1H), 1.70 (m, 1H), 2.05 (m, 1H),
2.50 (br s, NH), 3.75 (m, 1H), 3.80 (s, 3H), 3.85 (m, 1H), 4.05 (m,
1H), 4.65 (d, J = 5.1 Hz, 1H), 6.60 (d, J = 8.1 Hz, 1H), 6.80 (dd, J
= 8.0 and 2.7 Hz, 1H), 7.05 (d, J = 2.7 Hz, 1H), 7.40 7.50 (m, 5H).
Anal. Calcd for C19H21NO (279.38): C, 81.68; H, 7.58; N, 5.01.
Found: C, 81.70; H, 7.61; N, 5.02.
4e: solid; mp 130 131 °C.
IR (KBr): = 3340, 2975, 2840, 1615, 1504, 1080 cm–1.
3i: solid; mp 151 152 °C.
IR (KBr): = 3345, 2975, 2850, 1600, 1490, 1065 cm–1.
1H NMR (CDCl3): = 1.35 (m, 1H), 1.50 (m, 1H), 1.65 (m, 1H),
1.85 (m, 1H), 2.15 (m, 1H), 2.30 (s, 3H), 3.75 (dt, J = 11.5 and 2.5
Hz, 1H), 3.90 (br s, NH), 4.15 (m, 1H), 4.40 (d, J = 2.8 Hz, 1H), 4.70
(d, J = 10.5 Hz, 1H), 6.70 (t, J = 8.0 Hz, 1H), 7.05 (dd, J = 8.0 and
0.8 Hz, 1H), 7.15 (dd, J = 8.0 and 1.5 Hz, 1H), 7.30–7.35 (m, 1H),
7.40–7.45 (m, 1H), 7.50–7.55(m, 2H).
1H NMR (CDCl3): = 1.30 1.55 (m, 4H), 2.15 (m, 1H), 3.40 (m,
1H), 3.60 (m, 1H), 3.75 (br s, NH), 4.60 (d, J = 2.2 Hz, 1H), 5.30 (d,
J = 5.1 Hz, 1H), 6.60 (d, J = 8.0 Hz, 1H), 6.80 (t, J = 8.1 Hz, 1H),
7.05 (t, J = 8.1 Hz, 1H), 7.25 (m, 2H), 7.40 (m, 1H), 7.50 (m, 1H).
EIMS: m/z (%) = M+ 333 (25), 302 (15), 288 (15), 274 (100), 251
(10), 218 (5), 188 (15), 173 (44), 130 (98), 115 (30).
3f: solid; mp 101 102 °C.
IR (KBr): = 3350, 2965, 2850, 1620, 1514, 1085 cm–1.
Anal. Calcd for C18H17NCl2O (334.24): C, 64.68; H, 5.13; N, 4.19;
Cl, 21.21. Found: C, 64.70; H, 5.19; N, 4.2O; Cl, 21.23.
1H NMR (CDCl3): = 1.45 (m, 1H), 2.15 (m, 1H), 2.30 (s, 3H), 2.75
(m, 1H), 3.60 (br s, NH), 3.70 (m, 1H), 3.80 (m, 1H), 4.65 (d, J =
3j: solid; mp 145 146 °C.
1
IR (KBr): = 3342, 2970, 2850, 1610, 1490, 1070 cm .
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J. S. Yadav et al.
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1H NMR (CDCl3): = 1.45 (m, 1H), 2.20 (m, 1H), 2.70 (m, 1H)
3.70 3.85 (m, 2H), 4.65 (d, J = 2.8 Hz, 1H), 5.25 (d, J = 8.0 Hz,
1H), 6.60 (d, J = 8.0 Hz, 1H), 6.80 (t, J = 7.9 Hz, 1H), 7.05 (t, J =
7.9 Hz, 1H), 7.30 (m, 2H), 7.45 (m, 1H), 7.60 (m, 1H).
EIMS: m/z (%) = M+ 295 (88), 264 (12), 236 (100), 224 (75), 193
(10), 167 (12), 121 (85), 115 (10), 77 (25).
Anal. Calcd for C19H21NO2 (295.38): C, 77.26; H, 7.17; N, 4.74.
Found: C, 77.28; H, 7.20; N, 4.77.
EIMS: m/z (%) = M+ 319 (100), 290 (20), 274 (70), 216 (20), 174
(35), 130 (67), 115 (35), 91 (20), 77 (40).
3o: solid; mp 155 156 °C.
IR (KBr): = 3340, 2990, 2870, 1605, 1520, 1135 cm .
1H NMR (CDCl3): = 1.60 (m, 1H), 2.25 (m, 1H), 2.75 (m, 1H)
3.70 3.80 (m, 3H), 3.85 (s, 3H), 4.70 (d, J = 2.2 Hz, 1H), 5.30 (d,
J = 8.0 Hz, 1H), 6.60 (d, J = 8.0 Hz, 1H), 6.80 (t, J = 8.0 Hz, 1H),
6.90 (t, J = 8.1 Hz, 1H), 7.05 (d, J = 8.0 Hz, 2H), 7.40 (m, 3H).
1
Anal. Calcd for C17H15NCl2O (320.22): C, 63.77; H, 4.72; N, 4.37;
Cl, 22.14. Found: C, 63.75; H, 4.73; N, 4.38; Cl, 21.19.
3k: solid; mp 150 152 °C.
IR (KBr): = 3340, 2995, 2880, 1620, 1490, 1143, 1025 cm .
1
1H NMR (CDCl3): = 1.40 1.60 (m, 4H), 2.20 (m, 1H), 2.30 (s,
3H) 3.45 (m, 1H), 3.55-3.65 (m, 2H), 4.60 (d, J = 2.3 Hz, 1H), 5.25
(d, J = 5.5 Hz, 1H), 6.50 (d, J = 8.2 Hz, 1H), 6.85 (dd, J = 8.2 and
2.1 Hz, 1H), 7.20 (d, J = 2.1 Hz, 1H), 7.35 (m, 4H).
EIMS: m/z (%) = M+ 281 (100), 236 (91), 174 (10), 146 (30), 121
(50), 77 (15).
Anal. Calcd for C18H19NO2 (281.35): C, 76.84; H, 6.81; N, 4.98.
Found: C, 76.87; H, 6.86; N, 4.99.
EIMS: m/z (%) = M+ 313 (100), 282 (45), 254 (10), 158 (10), 144
(32), 115 (10).
Acknowledgement
Anal. Calcd for C19H20NClO (313.83): C, 72.72; H, 6.42; N, 4.46;
Cl, 11.30. Found: C, 72.77; H, 6.44; N, 4.49; Cl, 11.33.
BVS & CM thank CSIR New Delhi for the award of fellowships.
3l: solid; mp 148 149 °C.
IR (KBr): = 3343, 2991, 2878, 1610, 1493, 1145, 1031 cm .
1
References
1H NMR (CDCl3): = 1.50 (m, 1H), 2.20 (m, 1H), 2.35 (s, 3H), 2.65
(m, 1H), 3.60 (br s, NH), 3.70 (m, 1H), 3.80 (m, 1H), 4.60 (d, J =
2.1 Hz, 1H), 5.20 (d, J = 8.0 Hz, 1H), 6.50 (d, J = 8.0 Hz, 1H), 6.85
(dd, J = 8.0 and 2.1 Hz, 1H), 7.10 (d, J = 0.8 Hz, 1H), 7.35 (d, J =
8.0 Hz, 2H), 7.40 (d, J = 8.0 Hz, 2H).
EIMS: m/z (%) = M+ 299 (100), 254 (81), 188 (28), 160 (32), 144
(40), 115 (22), 77 (15).
(1) IICT Communication No. 4727.
(2) (a) Weinreb, S. M. In Comprehensive Organic Synthesis,
Vol. 5; Trost, B. M.; Fleming, I., Eds.; Pergamon: Oxford,
1991, 401–449. (b) Boger, D. L.; Weinreb, S. M. Hetero
Diels-Alder Methodology in Organic Synthesis; Academic
Press: San Diego, 1987, Chap. 2 and 9. (c) Tietze, L. F.;
Kettschau, G. Top. Curr. Chem. 1997, 189, 1.
(3) (a) Yamada, N.; Kadowaki, S.; Takahashi, K.; Umezu, K.
Biochem. Pharmacol. 1992, 44, 1211. (b) Faber, K.;
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(c) Johnson, J. V.; Rauckman, S.; Baccanari, P. D.; Roth, B.
J. Med. Chem. 1989, 32, 1942.
(4) (a) Mohammed, E. A. Chem. Pap. 1994, 48, 261. (b)Chem.
Abstr. 1995, 123, 9315x.
(5) (a) Povarov, L. S. Russ. Chem. Rev. 1967, 36, 656.
(b) Babu, G.; Perumal, P. T. Tetrahedron Lett. 1998, 39,
3225.
(6) (a) Cabral, J.; Laszlo, P. Tetrahedron Lett. 1989, 30, 7237.
(b) Crousse, B.; Begue, J. P.; Delpon, D. B. Tetrahedron
Lett. 1998, 39, 5765.
(7) (a) Worth, D. F.; Perricone, S. C.; Elsager, E. F. J.
Heterocycl. Chem. 1970, 7, 1353. (b) Babu, G.; Perumal, P.
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Xie, M.; Sun, J. J. Org. Chem. 1999, 64, 6462.
(8) (a) Hadden, M.; Stevenson, P. J. Tetrahedron Lett. 1999, 40,
1215. (b) Makioka, Y.; Shindo, T.; Taniguchi, Y.; Takaki,
K.; Fujwara, Y. Synthesis 1995, 801.
Anal. Calcd for C18H18NClO (299.79): C, 72.11; H, 6.05; N, 4.67;
Cl, 11.83. Found: C, 72.14; H, 6.09; N, 4.68; Cl, 11.89.
3m: solid; mp 133 134 °C.
IR (KBr): = 3343, 3010, 2970, 2865, 1620, 1485, 1070 cm .
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1H NMR (CDCl3): = 1.50 m, 1H), 2.20 (m, 1H), 2.40 (s, 3H) 2.75
(m, 1H), 3.60 (br s, NH), 3.70 (m, 1H), 3.80 (m, 1H), 4.65 (d, J =
2.6 Hz, 1H), 5.25 (d, J = 8.0 Hz, 1H), 6.55 (d, J = 8.1 Hz, 1H), 6.80
(t, J = 8.0 Hz, 1H), 7.05 (t, J = 8.0 Hz, 1H), 7.20 (m, 2H), 7.25-7.35
(m, 1H).
EIMS: m/z(%) = M+ 265 (98), 234 (15), 220 (100), 174 (20), 130
(30), 105 (35), 91 (15).
Anal. Calcd for C18H19NO (265.35): C, 81.48; H, 7.72; N, 5.28.
Found: C, 81.49; H, 7.76; N, 5.30.
3n: solid; mp 14 146 °C.
IR (KBr): = 3345, 3015, 2985, 2860, 1615, 1490, 1050 cm–1.
1H NMR (CDCl3): = 1.30–1.60 (m, 4H), 2.10 (m, 1H), 3.40 (m,
1H) 3.55 (m, 1H), 3.80 (s, 3H), 4.65 (d, J = 1.8 Hz, 1H), 5.30 (d, J
= 5.6 Hz, 1H), 6.55 (d, J = 8.1 Hz, 1H), 6.75 (t, J = 8.1 Hz, 1H), 6.90
(d, J = 8.3 Hz, 2H), 7.05 (t, J = 8.1 Hz, 1H), 7.30 (d, J = 8.3 Hz, 2H),
7.35 (d, J = 8.3 Hz, 1H).
(9) Babu, B. S.; Balasubramanian, K. K. Acros Organics Acta
2000, 7, 1.
Synthesis 2001, No. 7, 1065–1068 ISSN 0039-7881 © Thieme Stuttgart · New York