Aldehydes and ketones as dipolarophiles: application to the synthesis of oxapenams

Abstract

2-Substituted (6a–e) and 2, 2-disubstituted oxapenams (6f–g) are obtained in one step by thermolysis of the β-lactam-based oxazolidinone 4 in the presence of aldehydes and reactive ketones respectively; the C(6)-substituted oxazolidinone variant 7 reacts with hexafluoroacetone to give the enantiomerically pure oxapenam 8.

References

1. R. D. G. Cooper, in Topics in Antibiotic Chemistry, ed. P. G. Sammes, Ellis Horwood Ltd., Chichester, 1980, vol. 3, p. 39; W. Dürckheimer, J. Blumbach, R. Lattrell and K. H. Scheunemann, Angew. Chem., Int. Ed. Engl., 1985, 24, 180; Recent Advances in the Chemistry and Biology of β-Lactams and β-Lactam Antibiotics, ed. G. I. Georg, Bioorg. Med. Chem. Lett.(Symposia-in-print No 8), 1993, 3, 2159.
2. T. T. Howarth, A. G. Brown and T. J. King, J. Chem. Soc., Chem. Commun., 1976, 266; D. Brown, J. R. Evans and R. A. Fletton, J. Chem. Soc., Chem. Commun., 1979, 282 The latter authors coined the term ‘clavam’..
3. (a) M. Wanning, H. Zähner, B. Krone and A. Zeeck, Tetrahedron Lett., 1981, 22, 2539; (b) D. L. Pruess and M. Kellett, J. Antibiot., 1983, 36, 208; (c) J. E. Baldwin, R. M. Adlington, J. S. Bryans, A. O. Bringhen, J. B. Coates, N. P. Crouch, M. D. Lloyd, C. J. Schofield, S. W. Elson, K. H. Baggaley, R. Cassels and N. Nicholson, Tetrahedron, 1991, 47, 4089.
4. W. Nagata, Pure Appl. Chem., 1989, 61, 325; M. Murakami, T. Aoki, M. Matsuura and W. Nagata, J. Antibiot., 1990, 43, 1441; H. R. Pfaendler, W. Hendel and U. Nagel, Z. Naturforsch. Teil B., 1992, 47, 1037; H. Wild and W. Hartwig, Synthesis, 1992, 1099; H. Wild, Tetrahedron Lett., 1993, 34, 285; H. R. Pfaendler, F. Weisner and K. Metzger, Bioorg. Med. Chem. Lett., 1993, 3, 2211; M. Botta, M. Crucianelli, R. Saladino, C. Mozzetti and R. Nicoletti, Tetrahedron, 1996, 52, 10205; H. R. Pfaendler and C. Medicus, Bioorg. Med. Chem. Lett., 1997, 7, 623; P. Couture and J. Warkentin, Can. J. Chem., 1998, 76, 241.
5. J. Brennan, G. Richardson and R. J. Stoodley, J. Chem. Soc., Chem. Commun., 1980, 49; G. H. Hakimelahi and G. Just, Can. J. Chem., 1981, 59, 941; J. Brennan, G. Richardson and R. J. Stoodley, J. Chem. Soc., Perkin Trans. 1, 1983, 649; D. Häbich, P. Naab and K. Metzger, Tetrahedron Lett., 1983, 24, 2559; B. H. Lee, A. Biswas and M. J. Miller, J. Org. Chem., 1986, 51, 106.
6. Synthetic routes to oxapenams: (a) S. Oida, A. Yoshida and E. Ohki, Chem. Pharm. Bull., 1978, 26, 448; (b) T. Kobayashi, Y. Iwano and K. Hirai, Chem. Pharm. Bull., 1978, 26, 1761; (c) P. H. Bentley and E. Hunt, J. Chem. Soc., Perkin Trans. 1, 1980, 2222; (d) J. C. Müller, V. Toome, D. L. Pruess, J. F. Blount and M. Weigele, J. Antibiot., 1983, 36, 217; (e) A. G. Brown, D. F. Corbett, J. Goodacre, J. B. Harbridge, T. T. Howarth, R. J. Ponsford, I. Stirling and T. J. King, J. Chem. Soc., Perkin Trans. 1, 1984, 635; (f) S. De Bernardo, J. P. Tengi, G. J. Sasso and M. Weigele, J. Org. Chem., 1985, 50, 3457; (g) D. Hoppe and T. Hilpert, Tetrahedron, 1987, 43, 2467; (h) B. Furman, Z. Kaluza and M. Chmielewski, J. Org. Chem., 1997, 62, 3135; (i) O. Neuss, B. Furman, Z. Kaluza and M. Chmielewski, Heterocycles, 1997, 45, 265.
7. O. Tsuge and S. Kanemasa, Advanced Heterocyclic Chemistry, ed. A. R. Katritzky, Academic Press, San Diego, 1989, vol. 45, p. 231.
8. (a) S. R. Martel, R. Wisedale, T. Gallagher, L. D. Hall, M. F. Mahon, R. H. Bradbury and N. J. Hales, J. Am. Chem. Soc., 1997, 119, 2309; (b) D. Planchenault, R. Wisedale, T. Gallagher and N. J. Hales, J. Org. Chem., 1997, 62, 3438; (c) S. R. Martel, D. Planchenault, R. Wisedale, T. Gallagher and N. J. Hales, Chem. Commun., 1997, 1987.
9. B. Furman, P. Krajewski, Z. Urbanczyk-Lipkowska, J. Frelek, Z. Kaluza, L. Kozerski and M. Chmielewski, J. Chem. Soc., Perkin Trans. 2, 1998, 1737.
10. D. A. Fletcher, R. F. McMeeking and D. J. Parkin, J. Chem. Inf. Comput. Sci., 1996, 36, 746.