ORGANIC
LETTERS
2008
Vol. 10, No. 2
173-175
A Facile Synthesis of 2-Methylquinolines
via Pd-Catalyzed Aza-Wacker Oxidative
Cyclization
Zuhui Zhang, Jiajing Tan, and Zhiyong Wang*
Hefei National Laboratory for Physical Science at Microscale, Joint Laboratory of
Green Synthetic Chemistry and Department of Chemistry, UniVersity of Science and
Technology of China, Hefei, Anhui, 230026, People’s Republic of China
Received September 19, 2007
ABSTRACT
A novel Pd-catalyzed Wacker-type oxidative cyclization under air is described. By using this cyclization, a series of 2-methylquinolines are
readily prepared with good yields under mild conditions.
Quinoline derivatives exist in many natural products,1 and
most of them exhibit various biological activities.2,3 Many
methods have been developed for the construction of
quinolines due to their great importance.2 Among various
synthetic routines, transition metal-catalyzed processes are
highly attractive.4 Metal-free paths to quinolines have also
been reported recently.5 Despite this progress, the develop-
ment of novel approaches to quinoline derivatives is still
desired because of their extreme significance.
Palladium-catalyzed processes play a vital role in the
synthesis of heterocycles.6 Recently, we reported a palladium-
catalyzed intramolecular oxypalladation of phenol derivatives
to synthesize 2-methylchromanones.7 In light of the success
of this Wacker-type oxidative cyclization, we turned our
attention to a more challenging aza-Wacker oxidative
cyclization.8-9 Compared to the previous report,7 the unusual
1,5-hydride alkyl to palladium migration is not observed in
this aza-Wacker reaction, but a dehydration process is
(4) For cobalt complex, see: Li, L.; Jones, W. D. J. Am. Chem. Soc.
2007, 129, 10707-10713. For rhodium complex, see: Beller, M.; Thiel,
O. R.; Trauthwein, H.; Hartung, C. G. Chem. Eur. J. 2000, 6, 2513-2522.
For titanium complex, see: Basuli, F.; Aneetha, H.; Huffman, J. C.;
Mindiola, D. J. J. Am. Chem. Soc. 2005, 127, 17992-17993. For gold
complex, see: Liu, X.-Y.; Ding, P.; Huang, J.-S.; Che, C.-M. Org. Lett.
2007, 9, 2645-2648. For palladium complexes, see: (a) Gabriele, B.;
Mancuso, R.; Salerno, G.; Ruffolo, G.; Plastina, P. J. Org. Chem. 2007,
72, 6873-6877. (b) Banwell, M. G.; Lupton, D. W.; Ma, X. H.; Renner,
J.; Sydnes, M. O. Org. Lett. 2004, 6, 2741-2744. (c) Hegedus, L. S.; Allen,
G. F.; Bozell, J. J.; Waterman, E. L. J. Am. Chem. Soc. 1978, 100, 5800-
5807. For iron complex, see: O’Dell, D. K.; Nicholas, K. M. J. Org. Chem.
2003, 68, 6427-6430. For nickel complex, see: Korivi, R. P.; Cheng, C.-
H. J. Org. Chem. 2006, 71, 7079-7082. For indium complex, see: Sakai,
N.; Annaka, K.; Konakahara, T. J. Org. Chem. 2006, 71, 3653-3655. For
zinc complex, see: Jiang, B.; Si, Y.-G. J. Org. Chem. 2002, 67, 9449-
9451. For tungsten complex, see: Sangu, K.; Fuchibe, K.; Akiyama, T.
Org. Lett. 2004, 6, 353-355.
(5) For recent publications, see: (a) Sandelier, M. J.; DeShong, P. Org.
Lett. 2007, 9, 3209-3212. (b) Tanaka, S.-y.; Yasuda, M.; Baba, A. J. Org.
Chem. 2006, 71, 800-803. (c) Wu, Y.-C.; Liu, L.; Li, H.-J.; Wang, D.;
Chen, Y.-J. J. Org. Chem. 2006, 71, 6592-6595. (d) Zhao, Y.-L.; Zhang,
W.; Wang, S.; Liu, Q. J. Org. Chem. 2007, 72, 4985-4988. (e) Hessian,
K. O.; Flynn, B. L. Org. Lett. 2006, 8, 243-246. (f Zhang, X. X.; Campo,
M. A.; Yao, T. L.; Larock, R. C. Org. Lett. 2005, 7, 763-766. (g) Janza,
B.; Studer, A. Org. Lett. 2006, 8, 1875-1878. (h) Zhang, Q.; Zhang, Z.
G.; Yan, Z. H.; Liu, Q.; Wang, T. Y. Org. Lett. 2007, 9, 3651-3653.
(6) See, for recent reviews: (a) Zeni, G.; Larock, R. C. Chem. ReV. 2006,
106, 4644-4680. (b) Zeni, G.; Larock, R. C. Chem. ReV. 2004, 104, 2285-
2310. (c) Nakamura, I.; Yamamoto, Y. Chem. ReV. 2004, 104, 2127-2198.
(d) Stoltz, B. M. Chem. Lett. 2004, 33, 362-367. (e) Wolfe, J. P.; Thomas,
J. S. Curr. Org. Chem. 2005, 9, 625-655.
(1) For representative reviews, see: (a) Michael, J. P. Nat. Prod. Rep.
2007, 24, 223-246. (b) Michael, J. P. Nat. Prod. Rep. 2005, 22, 627-646.
(c) Michael, J. P. Nat. Prod. Rep. 2004, 21, 650-668.
(2) For a review, see: Balasubramanian, M.; Keay, J. G. In Compre-
hensiVe Heterocyclic Chemistry II; Katritzky, A. R., Rees, C. W., Scriven,
E. F. V., Eds.; Pergamon Press: Oxford, UK, 1996; Vol. 5, p 245.
(3) For recent reports, see: (a) Ho¨glund, I. P. J.; Silver, S.; Engstro¨m,
M. T.; Salo, H.; Tauber, A.; Kyyro¨nen, H.-K.; Saarenketo, P.; Hoffre´n,
A.-M.; Kokko, K.; Pohjanoksa, K.; Sallinen, J.; Savola, J.-M.; Wurster, S.;
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K.; DeBernardo, S.; Bedard, P. W.; Camphausen, R. T.; Tam, S.; Tsao, D.
H. H.; Keith, J. C., Jr.; Nickerson-Nutter, C.; Shilling, A.; Young-Sciame,
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5300-5308.
10.1021/ol702153x CCC: $40.75
© 2008 American Chemical Society
Published on Web 12/15/2007