Preparation of α-amino-carboxylic acid derivatives via diastereoselective reactions of glycine enolate equivalents

Protected glycine analogues tethered to an imidazolidinone auxiliary undergo diastereoselective alkylation and acylation reactions in moderate to good yields (9–91%) with high levels of stereocontrol (generally >95% de). Subsequent alkylation of these derivatives has been demonstrated for the production of non-racemic α,α-disubstituted amino acid precursors. Diastereoselective aldol reactions are also found to proceed with good yields and excellent stereocontrol (62–84%, 93–95% de). Chiral auxiliary cleavage and hydrogenolysis of these adducts affords the β-hydroxy-α-amino acid derivatives with no observed erosion of optical purity.