Stereoselective synthesis of functionalized cyclic amino acid derivatives via a [2,3]-Stevens rearrangement and ring-closing metathesis

Org Lett. 2013 Sep 20;15(18):4770-3. doi: 10.1021/ol402129h. Epub 2013 Sep 3.

Abstract

Unnatural cyclic amino acids are valuable tools in biomedical research and drug discovery. A two-step stereoselective strategy for converting simple glycine-derived aminoesters into unnatural cyclic amino acid derivatives has been developed. The process includes a palladium-catalyzed tandem allylic amination/[2,3]-Stevens rearrangement followed by a ruthenium-catalyzed ring-closing metathesis. The [2,3]-rearrangement proceeds with high diastereoselectivity through an exo transition state. Oppolzer's chiral auxiliary was utilized to access an enantiopure cyclic amino acid by this approach, which will enable future biological applications.

Publication types

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

MeSH terms

  • Amination
  • Amino Acids, Cyclic / chemical synthesis*
  • Amino Acids, Cyclic / chemistry
  • Catalysis
  • Combinatorial Chemistry Techniques
  • Glycine / analogs & derivatives
  • Glycine / chemistry
  • Molecular Structure
  • Palladium / chemistry*
  • Ruthenium / chemistry*
  • Stereoisomerism

Substances

  • Amino Acids, Cyclic
  • Palladium
  • Ruthenium
  • Glycine