Configurationally Stable ( S )‐ and ( R )‐α‐Methylproline‐Derived Ligands for the Direct Chemical Resolution of Free Unprotected β 3 ‐Amino Acids

Reported herein is a chemical method for the direct resolution of unprotected racemic β‐substituted‐β‐amino acids (β 3 ‐AAs) that uses specially designed, stable, and recyclable α‐methylproline‐derived chiral ligands. The versatility of this methodology is unmatched by biocatalytic approaches. The method shows a broad synthetic generality for various aryl‐ or alkyl‐substituted β 3 ‐AAs, and the new nonracemizable ligands can be accessed readily. Furthermore, the presented method produces an excellent stereochemical outcome and has a fully recyclable source of chirality, and the reaction conditions are operationally simple and convenient. The procedure has also been successfully applied to the scalable synthesis of the anti‐HIV drug maraviroc.