The first enantioselective syntheses of vicinal difluoropyrrolidines and the first catalytic asymmetric synthesis mediated by the C₂ symmetry of a –CHFCHF– unit

Abstract

The first enantiopure vicinal difluorides of C₂ symmetry have been prepared by the introduction of fluorine at both centres in a single operation; the first asymmetric synthesis using a catalyst whose chirality depends on organofluorine asymmetry is described.

References

1. (a) V. Aoloshonok, in Biomedical Frontiers of Fluorine Chemistry, ed. I. Ojima, J. R. McCarthy and J. T. Welch, American Chemical Society Symposium Series, Washington, DC, 1996, vol. 639, pp. 26–41; (b) J. R. McCarthy, P. S. Sunkasa, D. P. Matthews, A. J. Bitonti, E. T. Jarvi, J. S. Sabol, R. J. Resvick, E. W. Huber, W. A. van der Donk, G. Yu and J. Stubbe, ibid., pp. 246–264; (c) M. Namchuk, C. Braun, J. D. McCarter and S. G. Withers, ibid., pp. 265–278; M. Namchuk, C. Braun, J. D. McCarter and S. G. Withers, ibid., pp. 279–293.
2. P. Bravo and G. Resnati, Tetrahedron Asymmetry, 1990, 1, 661.
3. D. Bouzard, P. Dicesare, M. Essiz, J. P. Jacquet, J. R. Kiechel, P. Remuzon, A. Weber, T. Oki, M. Masuyoshi, R. E. Kessler, J. Fungtomc and J. Desiderio, J. Med. Chem., 1990, 33, 1344.
4. (a) J. T. Welch and S. Eswarakrishnan, Fluorine in Bio-organic Chemistry, Wiley, New York, 1991; (b) J. A. Wilkinson, Chem. Rev., 1992, 92, 505.
5. E. Kun, E. Kirsten and M. L. Sharma, Proc. Natl. Acad. Sci. USA, 1977, 74, 4942.
6. H. Liu and H. Nohira, Liq. Crystal., 1996, 581.
7. C. K. Chen, Y. L. Hu, M. Spears, J. W. Hodby, B. M. Wanklyn, A. V. Narlikar and S. B. Samanta, J. Mater. Sci. Lett., 1996, 15, 886.
8. H. Plenio, R. Diodone and D. Badura, Angew. Chem., Int. Ed. Engl., 1997, 36, 156.
9. For a single example of a racemic vic-difluoro-2,3-dihydrobenzo[b] furan, see: R. Ruzziconi and G. V. Sebastiani, J. Heterocycl. Chem., 1980, 17, 1147.
10. For meso-difluorides see: (a) M. Hudlicky, J. Fluorine Chem., 1987, 36, 373; (b) A. Baklouti and R. El Gharbi, J. Fluorine Chem., 1979, 13, 297; (c) T. B. Patrick, S. Khazaeli, S. Nadji, K. Hering-Smith and D. Reif, J. Org. Chem., 1993, 58, 705; (d) G. A. Olah, J. T. Welch, Y. D. Vankar, M. Nojima, I. Kerekes and J. A. Olah, J. Org. Chem., 1979, 44, 3872.
11. S. Rozen and M. Brand, J. Org. Chem., 1986, 51, 3607.
12. M. Sato, T. Hirokawa, A. Hattori, A. Toyota and C. Kaneko, Tetrahedron: Asymmetry, 1994, 5, 975.
13. W. J. Middleton, J. Org. Chem., 1975, 40, 574; M. Hudlicky, Org. React., 1988, 35, 513.
14. D. F. Shellhamer, D. T. Austine, K. M. Gallego, B. R. Ganesh, A. A. Hanson, K. A. Hanson, R. D. Henderson, J. M. Prince and V. L. Heasley, J. Chem. Soc., Perkins Trans. 2, 1995, 861.
15. (a) A. I. Burmakov, L. A. Motnyak, B. V. Kunshenko, L. A. Alexeva and L. M. Yagupolskii, J. Fluorine Chem., 1981, 19, 151; (b) for a racemic route to mixtures of difluorosuccinic acid derivatives from maleic anhydride and F₂, see: R. G. Syvret, D. L. Vassilaros, D. M. Parees and G. P. Pez, J. Fluorine Chem., 1994, 67, 277.
16. R. L. Shriner and C. L. Furrow, Org. Synth., 1963, Coll. Vol. IV, 242.
17. Y. Gao, R. M. Hanson, J. M. Klunder, S. Y. Ko, H. Masamune and K. B. Sharpless, J. Am. Chem. Soc., 1987, 109, 5765.
18. R. O. Duthaler and A. Hafner, Angew. Chem., Int. Ed. Engl., 1997, 36, 43.
19. T. Katsuki and K. B. Sharpless, J. Am. Chem. Soc., 1980, 102, 5974.