A facile and convenient three-component coupling protocol for the synthesis of pyrano and furoquinolines

Article abstract of DOI:10.1246/cl.2003.222

Ceric ammonium nitrate (CAN) catalyzes efficiently the coupling of anilines, benzaldehydes and 3,4-dihydro-2H-pyran or 2,3-dihydrofuran to form the corresponding pyrano or furoquinolines in short reaction times and in high yields.

Full text of DOI:10.1246/cl.2003.222

222
Chemistry Letters Vol.32, No.3 (2003)
A Facile and Convenient Three-component Coupling Protocol for the Synthesis of Pyrano and
Furoquinolines1
N. Ravindranath, C. Ramesh, M. Ravinder Reddy, and Biswanath Dasꢀ
Organic Chemistry Division-I, Indian Institute of Chemical Technology, Hyderabad 500 007, India
(Received November 22, 2002; CL-020993)
Table 1. CAN catalysed preparation of pyrano and
furoquinolinesa
Ceric ammonium nitrate (CAN) catalyzes efficiently the
coupling of anilines, benzaldehydes and 3,4-dihydro-2H-pyran or
2,3-dihydrofuran to form the corresponding pyrano or furo-
quinolines in short reaction times and in high yields.
Aniline Benzaldehyde Olefine Isolated Product
(3) yield/% ratiob Ref
Entry
(1)
R1
(2)
R2
R3
n
cis:trans
a
b
c
d
e
f
g
h
i
H
H
Cl
H
H
H
H
H
H
H
H
H
H
H
Cl
H
H
H
H
H
Cl
H
H
Cl
OMe
Cl
Br
H
1
1
1
2
2
2
2
2
2
2
2
81
84
89
86
91
86
20:70 4b
25:75
15:85 4b
20:80 4b
30:70 4c
25:75 4c
Pyranoquinoline derivatives are known to possess various
biological properties including antiallergic and anti-inflamma-
tory activities.2 These compounds can be prepared by applying
aza-Diels–Alder reactions between imines and 3,4-dihydro-2H-
pyran (DHP). Generally, Lewis acids3;4 are employed to catalyze
such reactions. However, several Lewis acids are deactivated or
decomposed by nitrogen containing substrates.4c Some of the
Lewis acids are not easily available or expensive, require longer
reaction times and form the products with poor yields.
Recently we have discovered an efficient one-pot method for
the coupling of anilines, benzaldehydes and 3,4-dihydro-2H-
pyran or 2,3-dihydrofuran in the presence of catalytic amount of
ceric ammonium nitrate (CAN) to form the corresponding pyrano
and furoquinolines (Scheme 1, Table 1).
9310:90 4c
89
86
89
80
15:85 4c
CH3
Cl
CH(CH3)2
15:85 4b
30:70 4b
25:75
j
k
H
Cl
aProduct ratios were calculated from crude NMR spectral
values. bAll the products were characterized from their
spectral (1H NMR and MS) data.
Several anilines and benzaldehydes were treated with 3,4-
dihydro-2H-pyran or 2,3-dihydrofuran. CAN was found to
catalyze the reactions efficiently to afford various quinoline
derivatives. The reactions occurred at room temperature in short
reaction times.5 The products were obtained in high yields and
high diasteroselectivity. They were formed as a mixture of exo
and endo isomers which could be separated by column chroma-
tography over silica gel. The product ratio was determined by 1H
NMR spectra of the crude products.
treatment with 3,4-dihydro-2H-pyran or 2,3-dihydrofuran in the
absence of the catalyst. When the former were separately treated
with this pyran or furan derivative using CAN under the present
reaction conditions the desired reaction was found to occur
smoothly. Thus it is obvious that CAN catalyzed the aza-Diels–
Alder reaction between imines and 3,4-dihydro-2H-pyran or 2,3-
dihydrofuran to form the corresponding quinolines. CAN has
previously been employed6 for ring opening of epoxides through
a radical cation intermediate but in this case pyran or furan ring
was not opened. The structures of the products were settled from
their spectroscopic data.5 The spectral properties of the known
compounds were in good agreement with those reported earlier
(references in the Table).
In conclusion, we have developed an efficient one-pot
method for the synthesis of pyrano and furoquinoline derivatives
by applying three-component coupling reaction catalyzed by
CAN. The mild reaction conditions, utilization of an easily
available reagent as catalyst, operational simplicity, short reac-
tion times and high yields and greater diastereoselectivity of the
products are the advantages of the present procedure. This is the
first report of the application of CAN for the synthesis of
tetrahydroquinoline derivatives.
NH2
CHO
R3
CAN, MeCN
)
(
n
,
+
+
r.t., 20 min
O
R2
R1
O
O
R1
( )n
R1
( )n
R2
R3
+
R2
R3
N
N
H
H
4 (cis)
5 (trans)
Scheme 1.
The authors thank UGC and CSIR, New Delhi for financial
assistance.
The reaction proceeded through CAN catalyzed Aza-Diels–
Alder reaction between imines (which were formed in situ from
anilines and benzaldehydes) and 3,4-dihydro-2H-pyran or 2,3-
dihydrofuran. The role of CAN in this reaction is very clear. The
imines were found to be produced directly by the reaction
between anilines and benzaldehydes without the presence of
CAN. However, the imines could not form the products by
References and Notes
1
Part 12 in the series ‘‘Studies on Novel Synthetic Methodol-
ogies,’’ for part 11 see C. Ramesh, N. Ravindranath, and B.
Das, J. Chem. Res., Synop. (2001) (in press). IICT Commu-
Copyright Ó 2003The Chemical Society of Japan

Chemistry Letters Vol.32, No.3 (2003)
nication No. 011206.
223
7.05 (1H, t, J = 7.8 Hz ), 6.68 (1H, t, J = 7.8 Hz ), 6.56 (1H, d,
J = 7.8 Hz), 5.25 (1H, d, J = 8 Hz), 4.65 (1H, d, J = 3Hz),
3.78 (1H, brs), 3.40–3.62 (2H, m), 2.18 (1H, m), 1.56 (2H, m);
EIMS (m=z): 285 (Mþ), 206. Anal. Calcd. for C17H16ClNO:
C, 71.45; H, 5.64; N, 4.90%. Found: C, 71.28; H, 5.52; N,
4.92%. 5b: 1H NMR (200 MHz, CDCl3): ꢀ 7.35 (4H, s), 7.14
(1H, d, J = 7.8 Hz), 7.05 (1H, t, J = 7.8 Hz), 6.64 (1H, d, J =
8.0 Hz), 6.42 (1H, d, J = 8 Hz ) 4.58 (1H, d, J = 5.0 Hz), 4.08
(1H, m), 3.85 (3H, m), 2.45 (1H, m), 2.0 (1H, m), 1.72 (1H,
m); EIMS (m=z): 285 (Mþ), Anal. Calcd. for C17H16ClNO: C,
71.45; H, 5.64; N, 4.90%. Found: C, 71.22; H, 5.62; N, 4.82%.
Spectral and analytical data of the unknown pyranoquinolines
4k: 1H NMR (200 MHz, CDCl3): ꢀ 7.38 (4H, m), 7.15 (1H, s),
6.90 (1H, d, J = 8.0 Hz), 6.54 (1H, d, J = 8.2 Hz), 5.25 (1H, d,
J = 8 Hz), 4.60 (1H, brs), 3.40–3.68 (3H, m), 2.82 (1H, m),
2.10 (1H, m), 1.50 (4H, m), 1.32 (6H, d); EIMS (m=z): 341
(Mþ). Anal. Calcd. for C21H24ClNO: C, 73.77; H, 7.07; N,
2
a) J. V. Johnson, S. Rauckman, P. D. Baccanari, B. and Roth,
J. Med. Chem., 32, 1942 (1997). b) N. Yamada, S. Kadowaki,
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Diego (1987), Chaps. 2 and 9. b) S. M. Weinreb, in
‘‘Comprehensive Organic Synthesis,’’ ed. by B. M. Trost
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4
a) G. Babu and P. T. Perumel, Tetrahedron Lett., 39, 3225
(1998). b) Y. Ma, C. Qian, M. Xie, and J. Sun, J. Org. Chem.,
64, 6462 (1999). c) J. S. Yadav, B. V. S. Reddy, R. Srinivas,
Ch. Madhuri, and T. Ramalingam, Synlett, 2001, 240 and
references cited therein.
5
Preparation of Pyrano and Furanoquinolines: To a stirred
solution of benzaldehyde (1 mmol), aniline (1 mmol) and 3,4-
dihydro-2H-pyran or 2,3-dihydrofuran in acetonitrile
(10 mL) CAN (0.25 mmol) was added. The mixture was
continued to stirr at room temperature for 20 min. On
completion the solvent was removed and the mixture was
extracted with EtOAc (3 ꢁ 20 mL). The concentrated extract
was subjected to column chromatography over silica gel and
product was eluted with hexane–EtOAc (20:1). Spectral and
analytical data of the unknown furoquinolines 4b: 1H NMR
(200 MHz, CDCl3): ꢀ 7.40 (1H, d, J = 7.8 Hz), 7.36 (4H, s),
1
4.09%. Found: C, 73.72; H, 7.22; N, 4.22%. 5k: H NMR
(200 MHz, CDCl3): ꢀ7.40 (4H, m), 7.05 (1H, s), 6.95 (1H, d, J
= 8.0 Hz), 6.44 (1H, d, J = 8.0 Hz), 4.68 (1H, d, J = 5 Hz),
3.70–4.12 (3H, m), 2.82 (1H, m), 2.04 (1H, m), 1.40–1.82
(4H, m), 1.3(6H, d) EIMS ( m=z): (Mþ) 341. Anal. Calcd. for
C21H24ClNO: C, 73.77; H, 7.07; N, 4.09%. Found: C, 73.68;
H, 7.16; N, 4.18%.
6
N. Iranpoor, I. M. Baltork, and F. S. Zardaloo, Tetrahedron,
47, 9861 (1991).