K. C. Majumdar et al. / Tetrahedron Letters 52 (2011) 411–414
413
and to the CSIR (New Delhi) (S.S.) for their research fellowships.
We also thank the DST (New Delhi) for providing NMR, CHN-
analyzer, and IR spectrometers under the DST-FIST program.
I
R
I
R
R
H
N
TsN
N
Ts
Ts
6-endo
X
O
X
O
X
O
11
References and notes
3
10
X = NMe; O
R = Aryl group
5-exo
Base
1. (a) Murray, R. D. H.; Mendez, J.; Brown, S. A. The Natural Coumarins: Occurrence,
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O’Kennedy, R.; Thornes, R. D. Coumarins: Biology, Applications and Mode of
I
I
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R
R
Action; J. Wiley
& Sons: Chichester, UK, 1997; (c) Fylaktakidou, K. C.;
R
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H
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7
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I2
N
HN
N
H
NaHCO3
O
X
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5a: X = NMe; R = Me 13a: X = NMe; R = Me
9a: X=NMe;R=Me
9b: X=O;R=Me
5b:
13b:
X = O; R = Me
X = O; R = Me
Scheme 3. Plausible mechanism for the formation of 6-endo cyclized products.
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3 equiv of I2, 3 equiv of NaHCO3, and the use of CH3CN as the
solvent at room temperature afford the best result.
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were subjected to the molecular iodine-mediated cyclization at
optimized reaction condition to afford the cyclized products 7a–g
and 9a,b in 60–95% yields. An introduction of a substituent at
the terminal position of the alkyne part has a considerable effect
on the yield of the reaction. Substituents were first introduced onto
the aromatic ring attached to the alkyne. Electron-donating groups,
like Me and OMe in the para position, gave good yields while an
electron-withdrawing group, a Cl group, gave relatively poor yield
of 60%. The results are summarized in Table 2.
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bond, followed by nucleophilic attack of the aromatic p-electrons
on the activated triple bond. Loss of a proton from the intermediate
11 in the presence of NaHCO3 may give the 7,8-dihydropyridoqui-
nolone and pyridocoumarin derivatives 7 (Scheme 3). In case of the
substrates 5a,b, initially formed 7,8-dihydro derivatives 13a,b
might have got oxidized in the presence of I2 to afford the pyr-
idoquinolone 9a and pyridocoumarin 9b derivatives, respectively.
Linear-pyridoquinoline derivatives have been synthesized by
several methods14–20 which are expensive as well as multistep
reactions but angular-pyridoquinoline derivatives are not reported.
On the other hand, different methods including transition metal-
catalyzed reactions are available13 for the formation of the pyrido-
coumarin derivatives. However, organotin-mediated protocols
suffer from toxicity11 as well as separation problems12 and
palladium-mediated reactions need high temperature.13a,b In this
regard the iodine-mediated protocol seems to be superior to the
above methods as this involves very simple reaction conditions
and occurs at room temperature.
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25. Majumdar, K. C.; Sinha, B.; Ansary, I.; Chakravorty, S. Synlett 2010, 1407–1411.
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In conclusion we have developed an easy and efficient method
for the synthesis of angularly fused pyridoquinolone and pyrido-
coumarin derivatives with potential bioactivity. The reaction con-
dition is mild, and the products are easily isolable in good to
excellent yields. Moreover an iodine atom is introduced in the final
product which offers scope for further functionalization.
Acknowledgments
We thank the CSIR (New Delhi) and DST (New Delhi) for finan-
cial assistance. Two of us are grateful to the UGC (New Delhi) (I.A.)