furoquinolines especially the dihydrofuroquinolines which
are widely distributed in quinoline alkaloids.8 Herein, we
present a useful single step reaction involving the reduc-
tionꢀcyclizationꢀrearrangement process to new dihydro-
furoquinolines starting from azido-cyclopropyl ketones 1.
Azides9 and cyclopropyl ketones,10 as useful building
blocks for the construction of nitrogen- or oxygen-containing
heterocyclic compounds, have been studied extensively.
However, to the best of our knowledge, few studies on the
synthetic utility of substrates bearing both azide and cyclo-
propyl ketone groups have been reported. For the purpose of
constructing the dihydrofuroquinoline skeleton, we designed
azido-cyclopropyl ketone and anticipated that when the
azido group was reduced to an amine, it subsequently
condensed with ketone to give the active intermediate
which might be converted to the dihydrofuroquinoline 2
(Scheme 1). Starting with the readily available material
of triazene 1-1, the azido-cyclopropyl ketone 1 was easily
achieved in three classic and functional group tolerant steps:
(1) the Claisen reaction to give triazene-1,3-diketone, (2) the
K2CO3-mediated cyclopropanation of triazene-1,3-diketone
with 1,2-dibromoethane to afford the triazene-cyclopropyl
ketone 1-2, (3) the reaction of triazene-cyclopropyl ketone
Scheme 1. Our Strategy for the Synthesis of Dihydrofuroquinolines
However, when the reaction was carried out under H2
(1 atm) in the presence of Pd/C, the 4-quinolone11 3a was
obtained instead of dihydrofuroquinoline 2a in 95% yield
(Scheme 2). The substrates of 1k and 1r can also be
converted to their corresponding 4-quinolone 3k and 3r
in high yields (90ꢀ91%) under H2 reduction conditions
(Scheme 2).
1-2 with NaN3 in the presence of BF3 OEt2/TFA to give
azido-cyclopropyl ketone 1 (Scheme 1 and Supporting
Information).
To test our hypothesis, we initially treated the azido-
cyclopropyl ketone 1a with PPh3 in THF. We indeed
achieved the desired product 2a in 28% yield. Although
various conditions, including solvents and reaction tem-
peratures, were tested, the yield could not be increased.
3
Scheme 2. Reducing Azido-cyclopropyl Ketone 1 with PPh3 and
Pd/CꢀH2
€
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Chem., Int. Ed. 2011, 50, 1702. (j) Lu, B.; Luo, Y.; Liu, L.; Ye, L.; Wang,
Y.; Zhang, L. Angew. Chem., Int. Ed. 2011, 50, 8358. (k) Huo, Z.; Gridnev,
I. D.; Yamamoto, Y. J. Org. Chem. 2010, 75, 1266. (l) Wang, Y.-F.; Toh,
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Wang, K.; Dong, D. J. Org. Chem. 2008, 73, 8089. (c) Ma, S.; Lu, L.;
Zhang, J. J. Am. Chem. Soc. 2004, 126, 9645. (d) Bowman, R. K.;
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Q.; Liang, F. Chem. Commun. 2011, 47, 12394. (h) Hu, B.; Xing, S.;
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To improve the yield of the dihydrofuroquinoline, other
reaction conditions were tried. Upon treating azido-cyclo-
propyl ketone 1a with AuPPh3Cl in CH2Cl2 at 50 °C, the
starting material was recovered in 90% yield, and no trace
of the desired quinoline compound was obtained (entry 1,
Table 1). Further screening among various metal catalysts
revealed that both Rh2(O2CCH3)4 and InCl3 gave full
recovery of the starting material (entries 2 and 3). To our
delight, heating the substrate 1a with FeCl2 in CH2Cl2
at 50 °C afforded the desired quinoline 2a in 10% yield
(entry 4). When the reaction was carried out using
Ru(PPh3)3Cl2 as the catalyst in CH2Cl2 at 50 °C, the yield
increased to 20% (entry 5). To optimize the result, the
effect of the solvents was further investigated. Changing
the solvent to toluene, DMF, CH3CN, and EtOH did
improve the yield from 20% to 30%, 55%, 64%, and 56%,
respectively (entries 6ꢀ9). Interestingly, when the reaction
was carried out in EtOH, the byproduct 2a0 (35% yield)
was obtained with the desired product 2a (56% yield).
ꢀꢁ
ꢁ
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Y.; Kurahashi, T.; Matsubara, S. J. Am. Chem. Soc. 2009, 131, 7494.
Org. Lett., Vol. 15, No. 6, 2013
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