Operationally Convenient and Scalable Asymmetric Synthesis of (2S)- and (2R)-α-(Methyl)cysteine Derivatives through Alkylation of Chiral Alanine Schiff Base Ni^IIComplexes

This research demonstrates that the methylation of N-benzyl cysteine Schiff bases derived Ni(II) complexes leads to the formation of the corresponding dehydroalanine containing products and cannot be used for preparation of the target -(methyl)cysteine. In sharp contrast, the alternative strategy involving the thiomethylation of the Ni(II) complexes of alanine Schiff bases, is viable and practically attractive approach affording the desired -(methyl)cysteine containing derivatives. This work also reveals a significant, and rather unexpected, difference in the stereochemical performance of proline and 3,5-dihydro-4H-dinaphth[2,1-c:1',2'-e]azepine derived chiral ligands, showing a clear superiority of the former in terms of chemical yields and diastereoselectivity of the -(methyl)cysteine products formation.