New symmetry-breaking deprotonation reactions of cyclic imides using a chiral lithium amide base

Abstract

Treatment of various N-substituted succinimides, possessing additional three-, four- or five-membered ring-fusion, with a mixture of chiral lithium amide base and Me₃SiCl, enables enantioselective silylation to give products in up to 95% ee.

References

1. For reviews, see P. O'Brien, J. Chem. Soc., Perkin Trans. 1, 1998, 1439; P. J. Cox and N. S. Simpkins, Tetrahedron: Asymmetry, 1991, 2, 1; N. S. Simpkins, Advances in Asymmetric Synthesis, ed. G. R. Stephenson, Blackie Academic, 1996; K. Koga, Pure Appl. Chem., 1994, 66, 1487.
2. For leading references in these two areas, see A. J. Blake, S. M. Westaway and N. S. Simpkins, Synlett, 1997, 919 (sulfoxides) R. A. Ewin, D. A. Price, N. S. Simpkins, A. M. MacLeod and A. P. Watt, J. Chem. Soc., Perkin Trans. 1, 1997, 401 (organometallics).
3. We have recently described an enantioselective elimination reaction akin to the process outlined in Scheme 1, see C. D. Jones, N. S. Simpkins and G. M. P. Giblin, Tetrahedron Lett., 1998, 39, 1023.
4. The starting imide 5 was prepared via reaction of the corresponding anhydride (J. J. Tufariello, A. S. Milowsky, M. Al-Nuri and S. Goldstein, Tetrahedron Lett., 1987, 28, 267) with aniline, see A. L. J. Beckwith and D. R. Boate, J. Org. Chem., 1988, 53, 4339. See also A. Mustafa, S. M. A. D. Zayed and S. Khattab, J. Am. Chem. Soc., 1956, 78, 145 for an alternative synthesis, and ref. 9.
5. In the past we have observed increased rates of metallation by addition of LiCl to lithium amides, see for example D. A. Price, N. S. Simpkins, A. M. MacLeod and A. P. Watt, Tetrahedron Lett., 1994, 35, 6159; B. J. Bunn, N. S. Simpkins, Z. Spavold and M. J. Crimmin, J. Chem. Soc., Perkin Trans. 1, 1993, 3113 Recently, little effect of LiCl on the rate of deprotonation of a simple ketone by LDA was observed, see M. Majewski and P. Nowak, Tetrahedron Lett., 1998, 39, 1661.
6. These reactions were modelled on analogous substitutions of episulfones that we examined previously, see A. P. Dishington, R. E. Douthwaite, A. Mortlock, A. B. Muccioli and N. S. Simpkins, J. Chem. Soc., Perkin Trans. 1, 1997, 323.
7. M. J. Milewska, M. Gdaniec and T. M. Polonski, J. Org. Chem., 1997, 62, 1860.
8. T. Mukaiyama, H. Yamashita and M. Asami, Chem. Lett., 1983, 385.
9. For details of the preparation and enantioselective reduction of these types of meso-imide, see M. Ostendorf, R. Romagnoli, I. C. Pereiro, E. C. Roos, M. J. Moolenaar, W. N. Speckamp and H. Hiemstra, Tetrahedron: Asymmetry, 1997, 8, 1773.