Ethynyl Ketene-S,S-acetals: The Highly Reactive
Electron-Rich Dienophiles and Applications in
the Synthesis of 4-Functionalized Quinolines via a
One-Pot Three-Component Reaction
Yu-Long Zhao,* Wei Zhang, Shuang Wang, and Qun Liu*
FIGURE 1. Structures of ketene dithioacetals.
Department of Chemistry, Northeast Normal UniVersity,
Changchun, 130024, People’s Republic of China
workers described a novel approach to tetrahydroquinolines via
the aza-Diels-Alder (Povarov) reaction of ketene dithioacetals
9
B (Figure 1) with N-arylimines.
During the course of our studies on the chemistry of
4
a,b,5a-c,6,8,10
ReceiVed January 12, 2007
functionalized ketene dithioacetals,
a series of
R-ethynyl ketene-S,S-acetals, namely the alkylthio activated 1,3-
enynes (Figure 1, C), were prepared in high yields via a
consecutive Vilsmeier-Haack and dehydrochlorination reaction
1
1
starting from easily available R-acetyl ketene dithioacetals
1
2
under mild conditions. As synthetic applications of these
electron-rich enynes, we have described the self-coupling
reactions of the R-ethynyl ketene cyclic dithioacetals to the
corresponding heteroatom-substituted expanded 1,3-dithiolan-
1
3a
13b
[
5]radialene and alkyne-spaced TTFs. Interestingly, when
An efficient synthetic method for 4-functionalized quinoline
derivatives, 4-((1,3-dithian-2-ylidene)methyl)quinolines, has
been developed. Mediated by trifluoromethanesulfonic acid,
ethynyl ketene-S,S-acetals can react in a one-pot procedure
with various arylamines and aldehydes under mild conditions
to give the corresponding quinoline derivatives in good to
high yields via a consecutive arylimine formation, regiospe-
cific aza-Diels-Alder (Povarov) reaction, and reductive
amination.
the addition reactions of carboxylic acids to R-ethynyl ketene
dithioacetals were conducted in the absence of catalysts, the
addition was found to occur at the carbon-carbon triple bond
in a highly chemo- and regioselective manner. The above
results provided us with a more complete understanding of how
to use the electron-rich carbon-carbon triple bond of the
alkylthio activated 1,3-enynes. In this paper, the aza-Diels-
1
4
(5) For selected examples, see: (a) Dong, D.; Bi, X.; Liu, Q.; Cong, F.
Chem. Commun. 2005, 3580-3582. (b) Bi, X.; Dong, D.; Li, Y.; Liu, Q.
J. Org. Chem. 2005, 70, 10886-10889. (c) Zhao, L.; Liang, F.; Bi, X.;
Sun, S.; Liu, Q. J. Org. Chem. 2006, 71, 1094-1098. (d) Peruncheralathan,
S.; Khan, T. A.; Ila, H.; Junjappa, H. J. Org. Chem. 2005, 70, 10030-
10035. (e) Panda, K.; Suresh, J. R.; Ila, H.; Junjappa, H. J. Org. Chem.
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K.; Ila, H.; Junjappa, H. J. Org. Chem. 2003, 68, 3966-3975. (g) Rao, H.
S. P.; Sivakumar, S. J. Org. Chem. 2006, 71, 8715-8723.
Functionalized ketene dithioacetals, with the general structure
A as shown in Figure 1, are versatile intermediates in organic
1-3
synthesis and R-EWG ketene dithioacetals (EWG ) electron
withdrawing group) have proven to be important building blocks
1,4
in the construction of substituted aromatic and heterocyclic
(6) (a) Yin, Y.; Wang, M.; Liu, Q.; Hu, J.; Sun, S.; Kang, J. Tetrahedron
Lett. 2005, 46, 4399-4402. (b) Sun, S.; Zhang, Q.; Liu, Q.; Kang, J.; Yin,
Y.; Li, D.; Dong, D. Tetrahedron Lett. 2005, 46, 6271-6274. (c) Pan, W.;
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Q.; Li, J.; Sun, S.; Liu, Q. Tetrahedron Lett. 2006, 47, 6071-6074. (e)
Zhang, Q.; Liu, Y.; Wang, M.; Liu, Q.; Hu, J.; Yin, Y. Synthesis 2006,
3009-3014.
compounds.1,5 Some recent research has revealed that the
coupling reaction at the R-carbon of functionalized ketene
dithioacetals is reliable and incorporates a wide variety of
6,7
functionalized ketene dithioacetals and carbon or heteroatom
8
electrophiles. Recently, in a significant report, Beaton and co-
(7) (a) Okauchi, T.; Tanaka, T.; Minami, T. J. Org. Chem. 2001, 66,
3
924-3929. (b) Yahiro, S.; Shibata, K.; Saito, T.; Okauchi, T.; Minami,
(
1) For reviews on R-oxo ketene-S,S-acetals, see: (a) Dieter, R. K.
T. J. Org. Chem. 2003, 68, 4947-4950.
Tetrahedron 1986, 42, 3029-3096. (b) Junjappa, H.; Tla, H.; Asokan, C.
V. Tetrahedron 1990, 46, 5423-5506. (c) Elgemeie, G. H.; Sayed, S. H.
Synthesis 2001, 1747-1771.
(8) (a) Wang, M.; Xu, X. X.; Liu, Q.; Xiong, L.; Yang, B.; Gao, L.
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Zhang, Q.; Xu, X. X. Synth. Commun. 2004, 34, 463-469.
(9) Cheng, D.; Zhou, J.; Saiah, E.; Beaton, G. Org. Lett. 2002, 4, 4411-
4414.
(2) For synthesis and synthetic application of phosphonoketene dithio-
acetals, see: (a) Minami, T.; Okauchi, T.; Matsuki, H.; Nakamura, M.;
Ichikawa, J.; Ishida, M. J. Org. Chem. 1996, 61, 8132-8140. (b) Kouno,
R.; Okauchi, T.; Nakamura, M.; Ichikawa, J.; Minami, T. J. Org. Chem.
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Synth. Catal. 2006, 348, 1986-1990.
1
998, 63, 6239-6246.
3) For synthesis and synthetic applications of fluorinated ketene
dithioacetals, see: (a) Muzard, M.; Portella, C. J. Org. Chem. 1993, 58,
(
2
1
9-31. (b) Pirrung, M. C.; Rowley, E. G.; Holmes, C. P. J. Org. Chem.
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(12) Dong, D.; Liu, Y.; Zhao, Y.-L.; Qi, Y.; Wang, Z.; Liu, Q. Synthesis
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(4) For selected examples, see: (a) Bi, X.; Dong, D.; Liu, Q.; Pan, W.;
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1
(14) Zhao, Y.-L.; Liu, Q.; Zhang, Y.-F.; Sun. S.-G.; Li, Y.-N. Synlett
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0.1021/jo070069q CCC: $37.00 © 2007 American Chemical Society
Published on Web 05/25/2007
J. Org. Chem. 2007, 72, 4985-4988
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