Diastereoselective 1,3‐Dipolar Cycloaddition Reactions between Azomethine Ylides and Chiral Acrylates Derived from Methyl (S)‐ and (R)‐Lactate – Synthesis of Hepatitis C Virus RNA‐Dependent RNA Polymerase Inhibitors

Abstract

AbstractHighly endo‐diastereoselective 1,3‐dipolar cycloadditions between acrylates derived from methyl (R)‐ and (S)‐lactate, as chiral dipolarophiles, and azomethine ylides derived from glycine and α‐substituted amino acids are described. The origins of the observed excellent stereocontrol are interpreted on the basis of computational studies on model systems. This methodology was successfully employed for the first asymmetric synthesis of both enantiomers, as well as of its racemic form, of a biologically active pyrrolidine (hepatitis C virus inhibitor) incorporating a leucine residue and a 2‐thienyl group. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)