Synthesis of prolines by enantioselective 1,3-dipolar cycloaddition of azomethine ylides and alkenes catalyzed by chiral phosphoramidite-silver(I) complexes

Abstract

The endo-diastereo- and enantioselective 1,3-dipolar cycloaddition of azomethine ylides and electrophilic alkenes is efficiently catalysed by chiral phosphoramidite-silver(I) perchlorate complexes. The reaction allows the presence of different types of substituents in the 1,3-dipole and can be applied to the synthesis of enantiomerically enriched, highly substituted prolines. This methodology was applied to the total synthesis of the inhibitors of the hepatitis C virus (HCV). Computational studies support a two-step mechanism predicting exactly the experimental results and the origin of both the diastereo- and enantioselections, as well as a reasonable explanation concerning the different reaction rates observed for some substrates.