Conformationally defined piperazine bis(N-oxides) bearing amino acid derived side chains

Abstract

The preparation of a number of piperazine derivatives bearing amino acid substituents on the nitrogen is described; these compounds undergo oxidation with MCPBA to yield bis(N-oxides) in which both oxygen atoms are axially orientated and hydrogen bonded to the amide NHs, giving highly defined conformations to the molecules; the structure of the valine derivative (8c) was confirmed by X-ray analysis.

References

1. D. H. Appella, L. A. Christianson, I. L. Karle, D. R. Powell and S. H. Gellman, J. Am. Chem. Soc., 1996, 118, 13071; D. H. Appella, L. A. Christianson, D. A. Klein, D. R. Powell, X. Huang, J. J. Barchi Jr and S. H. Gellman, Nature, 1977, 387, 381; D. Seebach, M. Overhand, F. N. M. Kuhnle, B. Martinoni, L. Oberer, U. Hommel and H. Widmer, Helv. Chim. Acta, 1996, 79, 913; D. Seebach, P. E. Ciceri, M. Overhand, B. Jaun, D. Rigo, L. Oberer, U. Hommel and H. Widmer, Helv. Chim. Acta, 1996, 79, 2043.
2. I. A. O'Neil, N. D. Miller, J. Peake, J. V. Barkley, C. M. R. Low and S. B. Kalindjian, Synlett, 1993, 515; D. Miller, J. V. Barkley, C. M. R. Low and S. B. Kalindjian, Synlett, 1995, 617; I. A. O'Neil, N. D. Miller, J. V. Barkley, C. M. R. Low and S. B. Kalindjian, Synlett, 1995, 619; I. A. O'Neil, C. D. Turner and S. B. Kalindjian, Synlett, 1997, 777; I. A. O'Neil and A. J. Potter, Tetrahedron Lett., 1997, 38, 5731; I. A. O'Neil and A. J. Potter, Chem. Commun., 1998, 1487.
3. I. A. O'Neil, C. D. Turner and S. B. Kalindjian, Synlett, 1997, 777; M. Nakajima, M. Saito, M. Shiro and S. Hashimoto, J. Am. Chem. Soc., 1998, 120, 6419; M. B. Diana, M. Marchetti and G. Melloni, Tetrahedron: Asymmetry, 1995, 6, 1175.
4. R. N. Zuckermann, J. M. Kerr, S. B. H. Kent and W. H. Moos, J. Am. Chem. Soc., 1992, 114, 10646; H. Kessler, Angew. Chem., Int. Ed. Engl., 1993, 32, 543.