One-pot synthesis of 2-(trifluoromethyl)pyridines from N-silyl-1-aza-allyl anions with trifluoroacetylketene diethyl ketal or (E )-1,1,1-trifluoro-4-phenylbut-3-en-2-one

Abstract

The reaction of N-silyl-1-aza-allyl anions with trifluoroacetylketene diethyl ketal and (E )-1,1,1-trifluoro-4-phenylbut-3-en-2-one are described. The anions, which were prepared from an α-silyl carbanion of 3-methyl-5-(trimethylsilylmethyl)isoxazole [or 3-methyl-2-(trimethylsilylmethyl)pyridine] and para-substituted benzonitriles (R = H, p-Me, p-OMe, p-Cl, p-CF₃), reacted with a slight excess of trifluoroacetylketene diethyl ketal or (E)-1,1,1-trifluoro-4-phenylbut-3-en-2-one in dry tetrahydrofuran to afford the corresponding 2-(trifluoromethyl)pyridine derivatives in 75, 71, 78, 48, 46, 60, 83% yield, respectively.

References

1. J. K. Whitesell and M. A. Whitesell, Synthesis, 1983, 517 for earlier work, see: D. A. Evans, J. Am. Chem. Soc., 1970, 92, 7593; G. Wittig, R. Roderer and S. Fischer, Tetrahedron Lett., 1973, 3517.
2. R. T. Courts and A. F. Casy, in Pyridine and its Derivatives, Supplement IV, ed. R. A. Abramovitch, Wiley, New York, 1975, p. 445.
3. Organofluorine Compounds in Medical Applications, ed. R. Filler, Y. Kobayashi and L. M. Yagupoloskii, Elsevier, Amsterdam, 1993.
4. H. Yoshioka, C. Takayama and N. Matsuo, J. Synth. Org. Chem. Jpn., 1984, 42, 809.
5. T. Konakahara and K. Sato, Bull. Chem. Soc. Jpn., 1983, 56, 1241.
6. T. Konakahara and Y. Takagi, Heterocycles, 1980, 14, 393.
7. T. Konakahara and Y. Kurosaki, J. Chem. Res., 1989, (S) 130, (M) 1068.
8. T. Konakahara, N. Sugama and K. Sato, Heterocycles, 1992, 33, 157.
9. T. Konakahara, M. Hojahmat and K. Sujimoto, Heterocycles, 1997, 45, 271.
10. T. Konakahara, A. Watanabe and K. Sato, Heterocycles, 1985, 23, 383.
11. T. Konakahara, A. Watanabe, K. Maehara, M. Nagata and M. Hojahmat, Heterocycles, 1993, 35, 1171.
12. T. Konakahara, M. Sato, T. Haruyama and K. Sato, Nippon Kagaku Kaishi, 1990, 466.
13. O. Tsuge, K. Matsuda and S. Kanemasa, Heterocycles, 1983, 20, 593.
14. M. Hojo, R. Masuda and E. Okada, Synthesis, 1986, 1013.
15. D. Mead, R. Loh, A. E. Asato and R. S. H. Liu, Tetrahedron Lett., 1985, 26, 2873.
16. I. I. Gerus, A. V. Kropachev, M. G. Gorbonova, A. Ya. Ilchenko and V. P. Kukhar, Ukr. Khim. Zh. (Russ. Ed.), 1993, 59, 408 (Ukr. Chem. J. (Engl. Ed.), 1993, 59, 76).
17. W. F. Goure, J. Heterocycl. Chem., 1993, 30, 71.
18. I. Katsuyama, S. Ogawa, Y. Yamaguchi, K. Funabiki, M. Matsui, H. Muramatsu and K. Shibata, Synthesis, 1997, 1321.
19. M. T. Cocco, C. Congiu, V. Onnis, A. M. Bernard and P. P. Piras, J. Heterocycl. Chem., 1997, 34, 1283.