Asymmetric Synthesis of Bis(alpha-methylamino acid) via a BPB-Ni(II)-Ala Complex

Several bis(alpha-methylamino acid)s were synthesized by using alanine-Ni-2[N'-(N-benzylprolyl)-amino]benzophenone [BPB-Ni(II)-Ala] as chiral auxiliary with alpha,omega-dibromoalkane. The substitution reaction with different carbon chain length of alpha,omega-dibromoalkanes showed the various results. For 1,3-dibromopropane with BPB-Ni(II)-Ala complex, the mono-alkylation and elimination reaction occurred sequentially, then allylic substitution of BPB-Ni(II)-Ala complex was obtained; while 1,4-dibromobutane, 1,5-dibromopentane, and 1,6-dibromohexane were used, bis(alpha-methylamino acid) dimerization complexes were formed after the mono-alkylation reaction. The yields of the dimerzation complex intermediate products were 38%, 36% and 45%. Then 2,7-diamino-2,7-dimethyloctanedioic acid, 2,8-diamino-2,8-dimethyl-nonanedioic acid, and 2,9-diamino-2,9-dimethyldecanedioic acid were obtained by hydroyzing the corresponding bis(alpha-methylamino acid) complexes. The reaction of BPB-Ni(II)-Ala with 1,3-dibromopropane yielded an S-2-amino-2-methyl-4-pentenoic acid complex, which was then hydrolyzed to S-2-amino-2-methyl-4-pentenoic acid. Chiral auxiliary BPB was recovered in a 95% yield.