Concise stereoselective synthesis of 1-perfluoroalkyl enamines via the addition of N-lithiated amines to enol ethers and their subsequent metalation to form new functionalized enamines

Abstract

Addition of lithium amides derived from a range of cyclic, sterically demanding, and chiral amines, to trifluoromethyl (Z )-enol ethers 1 and 4, provides stereoselectively the corresponding (Z )-enamines 3a–e and 7 in good yields. This reaction has been extended to the perfluoroalkyl and chlorofluoroalkyl enol ethers (CF₂Cl, C₂F₅). The enamines can react with Bu^tLi to give vinylic anions and, after quenching with aldehydes and ethyl chloroformate, provide new functionalized enamines 12–16.

References

1. Organofluorine Chemicals and their Industrial Applications, ed. R. E. Banks, Halsted Press, New York, 1979; M. Hudlicky, in Chemistry of Organic Fluorine Compounds, Ellis Horwood, London, 1992; Organofluorine Compounds in Medicinal Chemistry and Biomedical Applications, ed. R. Fuller, Y. Kobayashi and L. Yagupolski, Elsevier, Amsterdam, 1993; Selective Fluorination in Organic and Bioorganic Chemistry, ed. J. T. Welch, ACS Symposium Series 456, Washington DC, 1991, pp. 164–173; P. N. Edwards, in Organofluorine chemistry: Principles and Commercial Applications, ed. R. E. Banks, B. E. Smart and J. C. Tatlow, Plenum Press, New York, 1994, pp. 501–541.
2. K. Brady, A. Wei, D. Ringe and R. H. Abeles, Biochemistry, 1990, 29, 7600; R. P. Dunlap, P. J. Stone and R. H. Abeles, Biochem. Biophys. Res. Commun., 1987, 145, 509; R. L. Stein, A. M. Strimpler, P. D. Edwards, J. J. Lewis, R. C. Mauger, J. A. Schwartz, M. M. Stein, D. A. Trainor, R. A. Wildonger and M. A. Zottola, Biochemistry, 1987, 26, 2682; C. A. Veale, J. R. Damewood, G. B. Steelman, C. Bryant, B. Gomes and J. C. Williams, J. Med. Chem., 1995, 38, 86; N. P. Peet, J. P. Burkhart, M. R. Angelastro, E. L. Giroux, S. Mehdi, P. Bey, M. Kolb, B. Neises and D. Schirlin, J. Med. Chem., 1990, 33, 394; T. Ueda, C. M. Kam and J. C. Powers, Biochem. J., 1990, 265, 539; H. L. Sham, H. Stein, C. A. Rempel, J. Cohen and J. J. Plattner, FEBS Lett., 1987, 220, 229; C. Tarnus, M. J. Jung, J. M. Rémy, S. Baltzer and D. Schirlin, FEBS Lett., 1989, 249, 47; D. V. Patel, K. Rielly-Gauvin, D. E. Ryono, C. A. Free, S. A. Smith and E. W. Petrillo Jr, J. Med. Chem., 1993, 36, 2431.
3. M. A. McClinton and D. A. McClinton, Tetrahedron, 1992, 48, 6555; R. Krishnamurti and G. K. S. Prakash, J. Org. Chem., 1991, 56, 984.
4. D. J. Burton, Z. Y. Yang and W. Qiu, Chem. Rev., 1996, 96, 1641; K. J. Uneyama, Synth. Org. Chem. Jpn, 1991, 49, 612; J. M. Percy, Contemp. Org. Synth., 1995, 251.
5. (a) J. P. Bégué and D. Mesureur, Synthesis, 1989, 309; (b) J. P. Bégué, D. Bonnet-Delpon, D. Mesureur, G. Née and S. W. Wu, J. Org. Chem., 1992, 57, 3807.
6. V. A. Soloshonok and T. Ono, Synlett, 1996, 919; P. Bravo, M. Crucianelli and M. Zanda, Tetrahedron Lett., 1995, 36, 3043.
7. R. D. Chambers, S. Partington and D. B. Speight, J. Chem. Soc., Perkin Trans. 1, 1974, 2673; W. Cen, Y. Ni and Y. Shen, J. Fluorine Chem., 1995, 73, 161.
8. W. Dmowski, J. Fluorine Chem., 1984, 26, 379; C. Portella and M. Iznaden, J. Fluorine Chem., 1991, 51, 1; W. Y. Huang, Y. S. Liu and L. Lu, J. Fluorine Chem., 1994, 66, 209; L. F. Jalander and J. E. Lönnqvist, Synth. Commun., 1996, 26, 3549.
9. H. Bürger, T. Dittmar and G. Pawelke, J. Fluorine Chem., 1995, 70, 89.
10. J. P. Bégué, F. Benayoud and D. Bonnet-Delpon, J. Org. Chem., 1995, 60, 5029; J. P. Bégué, D. Bonnet-Delpon, N. Fischer-Durand, A. Amour and M. Reboud-Ravaux, Tetrahedron: Asymmetry, 1994, 5, 1094; J. P. Bégué, D. Bonnet-Delpon and A. Kornilov, Synthesis, 1996, 4, 529.
11. D. Bonnet-Delpon, D. Bouvet, M. Ourévitch and M. H. Rock, Synthesis, 1998, 288.
12. J. P. Bégué, D. Bonnet-Delpon and M. H. Rock, J. Chem. Soc., Perkin Trans. 1, 1996, 1409.
13. J. P. Bégué, D. Bonnet-Delpon, D. Bouvet and M. H. Rock, J. Org. Chem., 1996, 61, 9111.
14. J. P. Bégué, D. Bonnet-Delpon, D. Mesureur and M. Ourévitch, Magn. Reson. Chem., 1991, 29, 675.
15. For preparation of enol ethers and enamine 3f see ref. 5(b).