Development of a polymer bound Wittig reaction and use in multi-step organic synthesis for the overall conversion of alcohols to β-hydroxyamines

Abstract

An efficient combinatorial access to β-hydroxyamines suitable for automation is achieved by the mild oxidation of alcohols to aldehydes by polymer supported perruthenate (PSP), the subsequent clean olefination of the obtained aldehydes by polymer supported Wittig reagents followed by the epoxidation of the olefins by dimethyldioxirane (DMDO), and the final aminolysis of the epoxides with various amines is described.

References

1. (a) F. Haunert, M. H. Bolli, B. Hinzen and S. V. Ley, J. Chem. Soc., Perkin Trans. 1, 1998, 2235; (b) S. V. Ley, M. H. Bolli, B. Hinzen, A.-G. Gervois and B. J. Hall, J. Chem. Soc., Perkin Trans. 1, 1998, 2239.
2. (a) F. Camps, J. Castells, J. Font and F. Vela, Tetrahedron Lett., 1971, 1715; (b) S. C. McKinley and J. W. Rakshys, jun, J. Chem. Soc., Chem. Commun., 1972, 134; (c) W. Heitz and R. Michels, Angew. Chem., Int. Ed. Engl., 1972, 11, 298; (d) W. Heitz and R. Michels, Liebigs Ann. Chem., 1973, 227; (e) W. T. Ford, in ACS Symposium Series 308: Polymeric Reagents and Catalysts, ed. W. T. Ford, ACS Washington, 1986, p. 155.
3. (a) B. Hinzen and S. V. Ley, J. Chem. Soc., Perkin Trans. 1, 1997, 1907; (b) B. Hinzen and S. V. Ley, J. Chem. Soc., Perkin Trans. 1, 1998, 1; (c) B. Hinzen, R. Lenz and S. V. Ley, Synthesis, 1998, in the press.
4. R. Curci, M. Fiorentino, L. Troisi, J. O. Edwards and R. H. Pater, J. Org. Chem., 1980, 45, 4758; W. Adam, R. Curci and J. O. Edwards, Acc. Chem. Res., 1989, 22, 205; W. Adam, J. Bialas and L. Hadjiarapoglou, Chem. Ber., 1991, 124, 2377.
5. I. Hughes, Tetrahedron Lett., 1996, 37, 7595.
6. M. Bernard and W. T. Ford, J. Org. Chem., 1983, 48, 326.
7. For homogenous Wittig reactions see e.g.H. J. Bestmann and O. Vostrowsky, in Topics in Current Chemistry, Wittig Chemistry, ed. F. L. Boschke, Springer-Verlag, Berlin, Heidelberg, New York, 1983, vol. 109, p. 85.
8. Deiodination is also observed in homogenous Wittig reactions with iodomethyltriphenylphosphonium iodide: D. Seyferth, J. K. Heeren, G. Singh, S. O. Grim and W. B. Hughes, J. Organomet. Chem., 1966, 5, 267; G. Stork and K. Zhao, Tetrahedron Lett., 1989, 30, 2173; H. J. Bestmann, H. C. Rippel and R. Dostalek, Tetrahedron Lett., 1989, 30, 5261.