Scale-up Synthesis of (<i>R</i>)- and (<i>S</i>)‑<i>N</i>‑(2-Benzoyl-4-chlorophenyl)-1-(3,4-dichlorobenzyl)pyrrolidine-2-carboxamide Hydrochloride, A Versatile Reagent for the Preparation of Tailor-Made α- and β‑Amino Acids in an Enantiomerically Pure Form

Unusual amino acids are of crucial importance to the synthesis of bioactive peptides and new chemical entities. Innovative methodology is always needed for the preparation of enantiomerically pure amino acids that does not rely on tedious resolution procedures. The proline-derived ligands (<i>R</i>)- and (<i>S</i>)-<i>N</i>-(2-benzoyl-4-chlorophenyl)-1-(3,4-dichlorobenzyl)­pyrrolidine-2-carboxamide are outstanding, versatile, and recyclable reagents for the synthesis of tailor-made α- and β-amino acids. Here we report initial studies of the scale-up synthesis of the HCl salt of these reagents on the 100 g scale. The results demonstrate an increased efficiency and environmental friendliness of the bench-scale procedure and provides a firm foundation for the manufacture on multikilogram and larger scales

Chemical Dynamic Thermodynamic Resolution and <i>S</i>/<i>R</i> Interconversion of Unprotected Unnatural Tailor-made α‑Amino Acids

Described here is an advanced, general method for purely chemical dynamic thermodynamic resolution and <i>S</i>/<i>R</i> interconversion of unprotected tailor-made α-amino acids (α-AAs) through intermediate formation of the corresponding nickel­(II)-chelated Schiff bases. The method features virtually complete stereochemical outcome, broad substrate generality (35 examples), and operationally convenient conditions allowing for large-scale preparation of the target α-AAs in enantiomerically pure form. Furthermore, the new type of nonracemizable axially chiral ligands can be quantitatively recycled and reused, rendering the whole process economically and synthetically attractive

Chemical Dynamic Thermodynamic Resolution and <i>S</i>/<i>R</i> Interconversion of Unprotected Unnatural Tailor-made α‑Amino Acids

Described here is an advanced, general method for purely chemical dynamic thermodynamic resolution and <i>S</i>/<i>R</i> interconversion of unprotected tailor-made α-amino acids (α-AAs) through intermediate formation of the corresponding nickel­(II)-chelated Schiff bases. The method features virtually complete stereochemical outcome, broad substrate generality (35 examples), and operationally convenient conditions allowing for large-scale preparation of the target α-AAs in enantiomerically pure form. Furthermore, the new type of nonracemizable axially chiral ligands can be quantitatively recycled and reused, rendering the whole process economically and synthetically attractive

Purely Chemical Approach for Preparation of d‑α-Amino Acids via (<i>S</i>)‑to‑(<i>R</i>)‑Interconversion of Unprotected Tailor-Made α‑Amino Acids

Unnatural (<i>R</i>)-α-amino acids (α-AAs) are in growing demand in the biomedical research and pharmaceutical industries. In this work, we present development of a purely chemical approach for preparation of (<i>R</i>)-α-AAs via (<i>S</i>)-to-(<i>R</i>)-interconversion of natural and tailor-made (<i>S</i>)-α-AAs. The method can be used on free, unprotected α-AAs and features a remarkable structural generality including substrates bearing tertiary alkyl chains and reactive functional groups. These attractive characteristics, combined with simplicity of reaction conditions and virtually complete stereochemical outcome, constitute a true methodological advance in this area, rivaling previously reported chemical and biocatalytic approaches