Synthesis of enantioenriched aza-proline derivatives through gold(I)-catalyzed cyclization of chiral α-hydrazino esters

J Org Chem. 2013 Jan 18;78(2):427-37. doi: 10.1021/jo302320v. Epub 2012 Dec 17.

Abstract

A selective gold(I)-catalyzed synthesis of chiral aza-proline derivatives has been developed by ring closure of enantioenriched α-hydrazino esters bearing an alkyne group. These are easily prepared through a synthetic strategy involving two key steps: organocatalyzed electrophilic amination of pent-4-ynal with dialkyl azodicarboxylate promoted by l-proline and functionalization of the triple bond by Sonogashira cross-coupling. This strategy allowed the preparation of a range of enantioenriched α-hydrazino esters that underwent ring closure by using Ph(3)PAuCl/AgBF(4) as a catalytic system. Under these conditions, 5-exo-dig cyclization was favored over 6-endo-dig and aza-proline derivatives were obtained in good yields without epimerization at the stereogenic center. Influence of the catalytic system, hydrazine protecting group and alkyne substitution on the cyclization step has also been investigated.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkynes / chemistry*
  • Aza Compounds / chemical synthesis*
  • Aza Compounds / chemistry
  • Catalysis
  • Cyclization
  • Esters
  • Gold / chemistry*
  • Hydrazines / chemical synthesis*
  • Hydrazines / chemistry*
  • Molecular Structure
  • Proline / analogs & derivatives*
  • Proline / chemical synthesis*
  • Proline / chemistry
  • Stereoisomerism

Substances

  • Alkynes
  • Aza Compounds
  • Esters
  • Hydrazines
  • Gold
  • Proline