α-Allyl-α-aryl α-amino esters in the asymmetric synthesis of acyclic and cyclic amino acid derivatives by alkene metathesis

J Org Chem. 2014 Jun 6;79(11):5359-64. doi: 10.1021/jo500707t. Epub 2014 May 14.

Abstract

Allylating agents were explored for the asymmetric synthesis of α-allyl-α-aryl α-amino acids by tandem N-alkylation/π-allylation. Cross-metathesis of the tandem product was developed to provide allylic diversity not afforded in the parent reaction; the synthesis of homotyrosine and homoglutamate analogues was completed. Cyclic α-amino acid derivatives could be accessed by ring-closing metathesis presenting a viable strategy to higher ring homologue of enantioenriched α-substituted proline. The eight-membered proline analogue was successfully converted to the pyrrolizidine natural product backbone.

Publication types

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

MeSH terms

  • Alkylation
  • Amino Acids, Cyclic / chemical synthesis*
  • Amino Acids, Cyclic / chemistry
  • Catalysis
  • Cyclization
  • Esters
  • Molecular Structure
  • Proline / analogs & derivatives*
  • Proline / chemistry*
  • Pyrrolizidine Alkaloids / chemical synthesis*
  • Pyrrolizidine Alkaloids / chemistry

Substances

  • Amino Acids, Cyclic
  • Esters
  • Pyrrolizidine Alkaloids
  • Proline