Hydroxylated pyrrolidines. Enantiospecific synthesis of all-cis 2,3,4,5-substituted pyrrolidine derivatives from serine

J Org Chem. 2002 Feb 22;67(4):1314-8. doi: 10.1021/jo011008+.

Abstract

We report the enantiospecific synthesis of the sterically congested all-cis 2,3,4,5-substituted pyrrolidines 4, 5, and 6, from either D- or L-serine. Hemiaminal intermediate 13 is converted to the fully substituted pyrrolidine 15 by way of a tandem Wittig-Michael reaction. The endo stereochemistry of the C-3 methyl group of compound 15 is set by stereoselective reduction of the double bond in 11, driven by a preference for hydrogenation from the rear side of the molecule. The all-cis configuration of these fully substituted pyrrolidines has been established by X-ray analysis of compound 6. Removal of the benzenesulfonyl group from the highly substituted and functionalized intermediate 15 is successfully accomplished by sodium naphthalenide reduction.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Catalysis
  • Crystallography, X-Ray
  • Molecular Conformation
  • Molecular Structure
  • Pyrrolidines / chemical synthesis*
  • Pyrrolidines / chemistry
  • Serine / analogs & derivatives*
  • Serine / chemical synthesis*
  • Serine / chemistry
  • Stereoisomerism

Substances

  • Pyrrolidines
  • Serine