Synthesis of trifluoromethyl substituted nucleophilic glycine equivalents and the investigation of their potential for the preparation of α-amino acids

The synthetic preparation of several Ni(II) complexed Schiff Bases of glycine will be introduced, as well as investigations into their reactivity and utility. Key to these investigations is the incorporation of electron-withdrawing trifluoromethyl groups within the framework of the conjugated system that stabilizes the enolate derived from the glycine component. Reactivity was evaluated for each of the complexes under phase transfer catalyzed alkylations with hydroxide bases, as well as the DBU catalyzed Michael Additions of optically active 3′-substituted-2-oxazoladinone amides of unsaturated carboxylic acids. It was found that the trifluoromethyl containing nucleophilic glycine equivalents were more reactive than their non-trifluoromethyl analogues in both reaction types. Therefore, the application of these modified Ni(II) complexes of glycine Schiff Bases are useful for the preparation of α-amino acids through phase transfer catalyzed alkylation as well as the preparation of optically pure β-substituted pyroglutamic acid precursors. [Display omitted] •Synthesis of trifluoromethyl substituted nucleophilic glycine equivalents.•Reactivity profile of Ni(II) complexes of glycine Schiff bases.•Alkylation of glycine.•Preparation of β-substituted pyroglutamic acids.•Increased C–H activity.