Synthesis of Prolines by Enantioselective 1,3-Dipolar Cycloaddition of Azomethine Ylides and Alkenes Catalyzed by Chiral Phosphoramidite-Silver(I) Complexes

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.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009) The enantioselective 1,3‐dipolar cycloaddition reaction of azomethine ylides and electrophilic alkenes is efficiently catalysed by chiral phosphoramidite–AgI complexes.This methodology was applied to the synthesis of enantiomerically enriched key compounds in the total synthesis of the inhibitors of the hepatitis C virus (HCV).