Asymmetric Metal‐Templated Approach to Amino Acids with a CF3‐Containing 3,2’‐Pyrrolidinyl Spirooxindole Core via a Michael/Mannich [3+2]‐Cycloaddition Reaction

Abstract

AbstractWe report here a practical protocol for the asymmetric synthesis of amino acids (AAs) with a CF3‐containing 3,2’‐pyrrolidinyl spirooxindole skeleton with three defined carbon stereocenters via a sequential Michael/Mannich [3+2]‐cycloaddition reaction. The coupling of a robust and stereochemically stable chiral dehydroalanine Ni(II) complex with various N‐2,2,2‐trifluoroethylisatin ketimines in the presence of triethylamine afforded a library of single diastereomeric complexes with a 3,2’‐pyrrolidinyl spirooxindole moiety in 36–71% yields. In particular, the change of base to LiOH allowed to obtain predominantly the Michael addition product in 76% yield. Finally, the decomposition of the obtained Ni(II) complexes with 3 N HCl provided the target complex AA with a 3,2’‐pyrrolidinyl spirooxindole core and (2S,4R)‐2,4‐diamino‐5,5,5‐trifluoropentanoic acid – an (S)‐norvaline derivative, together with easy recovery of the chiral auxiliary ligand for the synthesis of the starting dehydroalanine complex.