Design, Synthesis, and Evaluation of N‐(tert‐Butyl)‐Alanine‐Derived Chiral Ligands – Aspects of Reactivity and Diastereoselectivity in the Reactions with α‐Amino Acids

Abstract

N‐(2‐Benzoylphenyl)‐2‐(tert‐butylamino)propanamide has been designed as an advanced chiral auxiliary for the general asymmetric synthesis of α‐amino acids by in situ formation of the corresponding Schiff bases with amino acids followed by complexation with NiII ions and base‐catalyzed thermodynamic equilibrium. The first discovery stage described in this work has been focused on the exploration of stereocontrolling properties of the compound as a function of the reaction conditions and structural facets of various α‐amino acids. By using reactions with unprotected α‐amino acids as a model process, it was found that the corresponding Schiff base–NiII complexes were formed in a straightforward manner with both good to excellent chemical yields (73–99 %) and diastereoselectivity (74–26 to >98–2). The observed stereochemical outcome bodes well with the wide synthetic applications of this new type of 2‐(tert‐butylamino)propanamide‐derived chiral auxiliary.