Regiocontrolled syntheses of 3- or 5-fluorinated pyrazoles from 2,2-difluorovinyl ketones

Journal of Organic Chemistry

Volumn 61, Issue 8, 1996, Pages 2763-2769

  Ichikawa, Junji ^a   Kobayashi, Masakuni ^a   Noda, Yasuharu ^a   Yokota, Naoyuki ^a   Amano, Kazuhiro ^a   Minami, Toni ^a  

^a KYUSHU INSTITUTE OF TECHNOLOGY   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

ORGANOFLUORINE DERIVATIVE; PYRAZOLE DERIVATIVE;

ARTICLE; DRUG SYNTHESIS; REACTION ANALYSIS; STEREOCHEMISTRY;

EID: 0029948459     PISSN: 00223263     EISSN: None     Source Type: Journal    
DOI: 10.1021/jo951814e     Document Type: Article

References (42)

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17. For recent reports on the synthesis of 4-fluoropyrazoles, see: (a) Funabiki, K.; Ohtsuki, T.; Ishihara, T.; Yamanaka, H. Chem. Lett. 1995, 239-240. (b) Shi, X.; Ishihara, T.; Yamanaka, H.; Gupton, J. T. Tetrahedron Lett. 1995, 36, 1527-1530. (c) Bumgardner, C. L.; Sloop, J. C. J. Fluorine Chem. 1992, 56, 141-146. (d) Mohnes, H.; Wakselman, C. J. Org. Chem 1989, 54, 5618-5620.
18. For recent reports on the synthesis of 4-fluoropyrazoles, see: (a) Funabiki, K.; Ohtsuki, T.; Ishihara, T.; Yamanaka, H. Chem. Lett. 1995, 239-240. (b) Shi, X.; Ishihara, T.; Yamanaka, H.; Gupton, J. T. Tetrahedron Lett. 1995, 36, 1527-1530. (c) Bumgardner, C. L.; Sloop, J. C. J. Fluorine Chem. 1992, 56, 141-146. (d) Mohnes, H.; Wakselman, C. J. Org. Chem 1989, 54, 5618-5620.
19. For recent reports on the synthesis of 4-fluoropyrazoles, see: (a) Funabiki, K.; Ohtsuki, T.; Ishihara, T.; Yamanaka, H. Chem. Lett. 1995, 239-240. (b) Shi, X.; Ishihara, T.; Yamanaka, H.; Gupton, J. T. Tetrahedron Lett. 1995, 36, 1527-1530. (c) Bumgardner, C. L.; Sloop, J. C. J. Fluorine Chem. 1992, 56, 141-146. (d) Mohnes, H.; Wakselman, C. J. Org. Chem 1989, 54, 5618-5620.
20. For reports on the synthesis of 3- and 5-fluoropyrazoles. see: (a) Fabra, F.; Vilarrasa, J. J. Heterocycl. Chem 1978, 15, 1447-1449. Fabra, F.; Fos, E.; Vilarrasa, J. Tetrahedron Lett. 1979, 3179-3180. (b) Makino, K.; Yoshioka, H. J. Fluorine Chem 1988, 39, 435-440.
21. For reports on the synthesis of 3- and 5-fluoropyrazoles. see: (a) Fabra, F.; Vilarrasa, J. J. Heterocycl. Chem 1978, 15, 1447-1449. Fabra, F.; Fos, E.; Vilarrasa, J. Tetrahedron Lett. 1979, 3179-3180. (b) Makino, K.; Yoshioka, H. J. Fluorine Chem 1988, 39, 435-440.
22. For reports on the synthesis of 3- and 5-fluoropyrazoles. see: (a) Fabra, F.; Vilarrasa, J. J. Heterocycl. Chem 1978, 15, 1447-1449. Fabra, F.; Fos, E.; Vilarrasa, J. Tetrahedron Lett. 1979, 3179-3180. (b) Makino, K.; Yoshioka, H. J. Fluorine Chem 1988, 39, 435-440.
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25. Ichikawa, J.; Kobavashi, M.; Yokota, N.; Noda, Y.; Minami, T. Tetrahedron 1994, 50, 11637-11646.
26. 2 end, formation of a C-N double bond via double dehydrofluorination seems to occur more readily than the cyclization. in consideration of the fact that 1 reacted with primary amines to afford α-oxoketenimines in good yields. See: Ichikawa, J.; Yokota, N.; Kobayashi, M.; Amano, K.; Minami, T. Synlett 1996, in press.
27. Rudorf, W.-D.; Augstin, M. J. Prakt. Chem. 1978, 320, 585-599.
28. α repulsion. See: Chambers, R. D. Fluorine in Organic Chemistry; Antony Rowe: Chippenham, 1973; pp 1-13. Smart, B. E. In Organofluorine Chemistry: Principles and Commercial Applications; Banks, R. E., Smart, B. E., Tatlow, J. C., Eds.; Plenum Press: New York, 1994; pp 57-88. In anion 6, the pyrazole ring structure might depress the effect of anionic hyperconjugation, while causing the electronic repulsion between the fluorine and the β-nitrogen.
29. α repulsion. See: Chambers, R. D. Fluorine in Organic Chemistry; Antony Rowe: Chippenham, 1973; pp 1-13. Smart, B. E. In Organofluorine Chemistry: Principles and Commercial Applications; Banks, R. E., Smart, B. E., Tatlow, J. C., Eds.; Plenum Press: New York, 1994; pp 57-88. In anion 6, the pyrazole ring structure might depress the effect of anionic hyperconjugation, while causing the electronic repulsion between the fluorine and the β-nitrogen.
30. For the regioselective alkylation of N-unsubstituted pyrazoles, see: ref 3. Katritzky, A. R.; Lagowski, J. M. In Comprehensive Heterocyclic Chemistry: Potts, K. T., Ed.; Pergamon Press: Oxford. 1984; Vol. 5, pp 39-110. See also for recent examples: Luo, Y.; Potvin, P. G. J. Org. Chem. 1994, 59, 1761-1765. Valk, P. v. d.; Potvin, P. G. J. Org. Chem. 1994, 55, 1766-1770.
31. For the regioselective alkylation of N-unsubstituted pyrazoles, see: ref 3. Katritzky, A. R.; Lagowski, J. M. In Comprehensive Heterocyclic Chemistry: Potts, K. T., Ed.; Pergamon Press: Oxford. 1984; Vol. 5, pp 39-110. See also for recent examples: Luo, Y.; Potvin, P. G. J. Org. Chem. 1994, 59, 1761-1765. Valk, P. v. d.; Potvin, P. G. J. Org. Chem. 1994, 55, 1766-1770.
32. For the regioselective alkylation of N-unsubstituted pyrazoles, see: ref 3. Katritzky, A. R.; Lagowski, J. M. In Comprehensive Heterocyclic Chemistry: Potts, K. T., Ed.; Pergamon Press: Oxford. 1984; Vol. 5, pp 39-110. See also for recent examples: Luo, Y.; Potvin, P. G. J. Org. Chem. 1994, 59, 1761-1765. Valk, P. v. d.; Potvin, P. G. J. Org. Chem. 1994, 55, 1766-1770.
33. 10
34. For the MNDO and AM1 calculations on 3- and 5-fluoropyrazoles, see: Garcia, J.; Vilarrasa, J. Heterocycles 1988, 27, 1803-1807. Hammadi, A. E.; Mouhtadi, M. E.; Notario, R.; Abboud, J.-L. M.; Elguero, J. J. Chem. Res. (M) 1995, 1080-1096.
35. For the MNDO and AM1 calculations on 3- and 5-fluoropyrazoles, see: Garcia, J.; Vilarrasa, J. Heterocycles 1988, 27, 1803-1807. Hammadi, A. E.; Mouhtadi, M. E.; Notario, R.; Abboud, J.-L. M.; Elguero, J. J. Chem. Res. (M) 1995, 1080-1096.
36. 3: σ 118 8, 134.7. and 144.3) at the average values of both tautomers.
37. 13C chemical shift trends of regioisomeric pyrazoles have been reported for 3- and 5-hydroxypyrazoles and pyrazolecarboxylic esters. See: ref 4h. Sohár, P.; Fehér, O.; Tihanyi, E. Org. Magn. Reson. 1979, 12, 205-208.
38. Begtrup, M.; Boyer, G.; Cabildo, P.; Cativiela, C.; Claramunt, R. M.; Elguero, J.; Garcia, J. I.; Toiron, C.; Vedse, P. Magn. Reson. Chem. 1993, 31, 107-168.
39. γ-O3j).
40. 3 = aryl) are shifted downfieid by the anisotropic effect of the aryl group at the N-1 atom.
41. Ichikawa, J.; Miyazaki, S.; Fujiwara, M.; Minami, T. J. Org Chem. 1990, 60, 2320-2321. Fish, P. V.; Johnson, W. S.; Jones, G. S.; Tham, F. S.; Kullnig, R. K. J. Org. Chem. 1994, 59, 6150-6152.
42. Ichikawa, J.; Miyazaki, S.; Fujiwara, M.; Minami, T. J. Org Chem. 1990, 60, 2320-2321. Fish, P. V.; Johnson, W. S.; Jones, G. S.; Tham, F. S.; Kullnig, R. K. J. Org. Chem. 1994, 59, 6150-6152.