Polymer backbone disassembly: polymerisable templates and vanishing supports in high loading parallel synthesis

Abstract

In the synthesis of a library of N-alkyl-3-aza-8-oxabicyclo[3.2.1]octane-6,7-dimethanol derivatives, prepared from an 7-oxabicyclo[2.2.1]hept-2-ene-5,6-dimethanol derivative via ring opening metathesis polymerisation using Cl₂(Cy₃P)₂Ru[double bond, length half m-dash]CHPh, selective alkylation, ozonolytic scission of the polymer backbone and reductive alkylation, purification was facilitated by the differential solubility of the polymer intermediates.

References

1. N. K. Terrett, M. Gardner, D. W. Gordon, R. J. Kobylecki and J. Steele, Tetrahedron, 1995, 51, 8135; E. M. Gordon, R. W. Barrett, W. J. Dower, S. P. A. Fodor and M. A. Gallop, J. Med. Chem., 1994, 37, 1385; L. A. Thompson and J. A. Ellman, Chem. Rev., 1996, 96, 555; J. S. Früchtel and G. Jung, Angew. Chem., Int. Ed. Engl., 1996, 35, 17; D. J. Gravert and K. D. Janda, Chem. Rev., 1997, 97, 489.
2. V. Swali, N. J. Wells, G. J. Langley and M. Bradley, J. Org. Chem., 1997, 62, 4902.
3. V. C. Gibson, Adv. Mater., 1994, 6, 37; B. M. Novak and R. H. Grubbs, J. Am. Chem. Soc., 1988, 110, 960; B. M. Novak and R. H. Grubbs, J. Am. Chem. Soc., 1988, 110, 7542; R. H. Schrock, Acc. Chem. Res., 1990, 23, 158; D. S. Breslow, Prog. Polym. Sci., 1993, 18, 1141.
4. H. Han, M. M. Wolfe, S. Brenner and K. D. Janda, Proc. Natl. Acad. Sci. U.S.A., 1995, 92, 6419.
5. M. M. Shemyakin, Y. A. Ovchinnikov, A. A. Kinyushkin and I. V. Kozhevnikova, Tet. Lett., 1965, 2323; M. Mutter and E. Bayer, Angew. Chem., Int. Ed. Engl., 1974, 13, 88; E. Bayer, I. Gatfield, H. Mutter and M. Mutter, Tetrahedron, 1978, 34, 1829; M. Mutter, Tetrahedron Lett., 1978, 31, 2839 and 2843.
6. T. W. Greene and P. G. M. Wuts, Protective Groups in Organic Synthesis, 2nd edn., Wiley, 1991.
7. P. Schwab, M. B. France, Z. W. Ziller and R. H. Grubbs, Angew. Chem., Int. Ed. Engl., 1995, 34, 2039.
8. A. D. Benedicto, B. M. Novak and R. H. Grubbs, Macromolecules, 1992, 25, 5893.
9. A. F. Abdel-Magid, C. A. Maryanoff and K. G. Carson, Tetrahedron Lett., 1990, 31, 5595.