Large-scale asymmetric synthesis of novel sterically constrained 2′,6′-dimethyl- and α,2′,6′-trimethyltyrosine and -phenylalanine derivatives via alkylation of chiral equivalents of nucleophilic glycine and alanine

Asymmetric synthesis of (S)-2′,6′-dimethyltyrosine (DMT), (S)-2′,6′-dimethylphenylalanine (DMP), (S)-α,2′,6′-trimethyltyrosine (α-TMT) and (S)-α,2′,6′-trimethylphenylalanine (α-TMP) via reactions of 4′-benzyloxy-2′,6′-dimethylbenzyl bromide or 2′,6′-dimethylbenzylbromide with Ni(II)-complexes of the chiral Schiff base of glycine or alanine with (S)-o-[N-(N-benzylprolyl)amino]benzophenone were developed. Inexpensive and readily available reagents and solvents, a recyclable chiral auxiliary, simplicity of the experimental procedures and high chemical yields make this method synthetically attractive for preparing the target amino acids on a multi-gram scale.