| α-Amino acids are important for their biological uses as the backbone of peptides, protein and various activities in physiology and pharmacy. The research of amino acids was focused on the asymmetric synthesis of optically active α-amino acids due to their prominent values as intermediates of organic synthesis and starting materials for many chiral drugs. Glycine equivalent approach is one of the major asymmetric synthesis methods of α-amino acids. Several types of optically active non-proteinogenic α-amino acids were synthesized with Ni (II) complexes of glycine Shiff base by the electrophilic alkylation and Aldol reactions of the complexes. The process of the preparation of the chiral auxiliary 2-[N-(N'-benzylprolyl)-aminobenzo-phenone (BPB) were reinvestigated in detail. By reaction of proline and benzyl chloride under potassium hydroxide mediation in isopropyl alcohol, excellent yield (88-94%) of N-benzylproline (BP) was obtained. The BP was subsequently condensed with 2-aminobenzophenone in dichloromethane with thionyl chloride as activating reagent, thus the BPB was prepared in good yield (71-75%). Finally, the Ni (II) complexes of the Shiff base of glycine and alanine with BPB was synthesized in excellent yield of 90-95%. The whole process is reliable and practical. With the Ni (II) complexes in hand, extensive alkylation and Aldol reactions on the amino acid moieties were investigated. For the fairly strong C-H acidity on the α-C on the glycine or alanine, enolates were easily formed under mild base circumstances. The enolates may attack on electrophilic carbon of alkyl halide to afford α-alkylated glycine and alanine; attack on the carbonyl groups resulted β-hydroxy amino acids. In both cases, the chiral center on the α-C was efficiently controlled by the BPB auxiliary. The reactions on the Ni (II) complex of the Schiff base of glycine and alanine with BPB New Ni(II) complexes were formed by an Aldol reaction between the Ni(II) complexes of glycine Shiff base and formaldehyde or 2-furaldehyde. Acidolysis of Ni(II) complexes of serine Shiff base with hydrochloric acid and seperation by ion-exchange resin, the optically active serine was collected and the yield is more than 60% while the e.e. value is higher than 98%. Chiral auxiliary BPB was recovered in a 65-80% yield without any lose in optical purity. Electrophilic alkylation reactions of Ni(II) complexes of glycine Shiff base with 1-butyl bromide, 1-octyl bromide, 1-dodecyl bromide, benzyl bromide, phenethyl bromide, allyl bromide, 4-chloro-beznyl chloride, piperonyl bromide was used to produce another eight amino acids with a yield of 50-90% while e.e. value is over than 91%. The recovery yield of BPB is 60-71%. Twenty-six compounds was synthesized in this article. Among these compounds, four are new and unreported according to Chemical Abstract(CA). IR, MS, Elemental Analysis, 1H NMR spectra and X-rays single-crystal diffraction were used to identify the molecular structure and absolute configuration of the Ni(II) complexes and final amino acids. Two-demensional H-H NOESY NMR spectra was utilized in structural analysis of (S)-BPB-Ni-GLY for the first time to give support to following research of this system.
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