Study of Various Aspects of the Mechanism of Cα-Alkylation of α-Amino Acids under Phase-Transfer Salen Catalysis Conditions

Abstract

The stereodifferentiating ability of salen complexes of Cu(II), Ni(II), and Zn(II) ions in Cα-alkylation reactions of amino acids as phase-transfer catalysts (PTC) has been investigated. We found that substituents in the 3-position of the aromatic ring of the salicylidene moiety of the complexes have a particularly strong effect on catalytic activity. The highest efficiency was observed for the 3-methoxy-substituted salen complex of the Zn (II) — ee > 90%. DFT calculations showed that the stereodifferentiating ability of the catalyst depends on the ratio of propeller-like and cross-like conformational structures of dimeric binuclear salen complex molecules in the alkylation transition state. It was demonstrated that propeller-like conformational isomers, which predominate in the dimeric binuclear structure of 3-allyl-substituted salen complexes, correspond to the catalytically inactive form and inhibit asymmetric catalysis. In contrast, cross-like isomers, which dominate in the dimeric binuclear structure of 3-methoxy-substituted salen complexes, ensure high stereodifferentiating activity and promote asymmetric catalysis. The DFT calculation data correlates clearly with the experimental results.