3
naphthoquinones using iodine as oxidative reagent. Besides the
environmentally benign feature of iodine, the operation of this
iodine mediated conversion is also much simpler than Dudley’s
method which involves additional operations to remove the
mercurous acetate in between the reaction.
Supplementary data
Supplementary data associated with this article can be found in
the online version.
References and notes
The possible reaction mechanism was proposed as shown in
Scheme 1. The reaction was supposed to be initiated by the
nucleophilic attack of the olefinic double bond to iodine to form
the iodonium ion 10. The following decomposition of the
iodonium ion 10 might involve the attack from the neighboring
hydroxyl group to form the unstable iodide intermediate 11
which would automatically eliminate one molecular of HI to give
the angular naphthofuroquinone 8. In this process, one equivalent
of iodine will be consumed. An electron withdrawing R2 group
will decrease the nucleophilic ability of the olefinic double bond,
which might explain the inhibited reactivity of 7j-7l.
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O
O
O
O
O
OH
R1
R2
O
O
R1
R1
I+
R1
R2
I
I
I
OH
O
HO
OH
R2
R2
7
10
11
- H
- HI
O
O
O
O
H+
O
O
R1
R2
R1
R2
R1
R2
O+
O+
H
O
H2O
8
- H+
O
O
O
O
O
O
O
Paal-Knorr
O
R1
R2
R2
R2
O
OH R1
R1
O
12
6. Teimouria, M.B.; Khavasi, H.R. Tetrahedron 2007, 63, 10269-10275.
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13
9
H
Scheme 1. Proposed mechanism for the formation of 8 and 9.
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Synth. Commun. 2002, 32, 3099-3105; (b) Lee, Y.R.; Kim, B.S. Synth.
Commun. 2003, 33, 4123-4135.
Under acidic condition, hemiketal 12 could be formed through
the nucleophilic attack of H2O to the C-2 position of the
protonated angular naphthofuroquinone 8. The following
decomposition of hemiketal 12 would give the 1,4 diketone
intermediate 13, which would finally afford the linear
naphthofuroquinone 9 through a classic Paal-Knorr process.20
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(b) Lee, Y.R.; Kim, B.S. Synth. Commun. 2001, 31, 381-386.
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Tetrahedron Lett. 1997, 38, 837-840.
The
angular naphthofuroquinone 8j with an electron
withdrawing 2-bromophenyl R2 group failed to give the
corresponding linear isomer probably due to its reduced
protonation ability.
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I 1990, 441-445.
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5491.
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659-664.
In summary, a new method for highly regioselective synthesis
of both angular and linear naphthofuroquinones has been
developed via iodine-mediated hetero-annulation. Considering
the very mild reaction condition, high yields, high angular/linear
selectivity and noninvolvement of transitional metals, this
method might find great application in the synthesis of
naphthofuroquinones.
18. General method for the synthesis of 2-substitutednaphtho[1,2-b]furan-
4,5-dione 8: to a solution of 2-hydroxy-3-alkenyl-1,4-naphthoquinone
(0.5 mmol) in 5 mL THF was added iodine (0.5 mmol, 127 mg). The
mixture was stirred for 1-6 hours at room temperature until the full
conversion of the starting material and then diluted with 30 mL of H2O,
extracted with ethyl acetate (15 mL X 3). The combined organic layer
was washed with brine, dried over anhydrous sodium sulfate and
concentrated under vacuum. The residual was applied on a silica column
chromatography, eluting with a mixture of petroleum ether and ethyl
acetate (15:1) to afford the angular naphthofuroquinones 8. 2-
ethylnaphtho[1,2-b]furan-4,5-dione 8a: red solid, yield 89%, mp 136-
138oC, 1H NMR (400 MHz, CDCl3 ) δ 8.08 (d, J = 8.0 Hz, 1H), 7.69 (d, J
= 7.2 Hz, 1H), 7.65 (t, J = 7.2 Hz, 1H), 7.45 (td, J = 7.2, 1.2 Hz, 1H),
6.48 (s), 2.78 (q, J = 7.6 Hz, 2H), 1.34 (t, J = 7.6 Hz, 3H); 13C NMR (100
Acknowledgements
This work was supported by the National Nature Science
Foundation of China (No. 20672147; No. 21472247).