BPB-Ni(II)-Ala复合物法不对称合成双-α-甲基氨基酸

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

以2-N-(N'-苄基脯氨酰)-氨基二苯甲酮-镍(II)-丙基酸复合物为手性助剂,与不同碳链长度的二溴烷烃反应制备双-α-甲基氨基酸.其中,BPB-Ni(II)-Ala复合物与1,3-二溴丙烷发生取代-消除反应后生成烯丙基取代复合物中间体,产率高达90%,水解生成2-甲基-2-氨基-4-烯-戊酸;与1,4-二溴丁烷、1,5-二溴戊烷、1,6-二溴己烷可以实现双取代反应,但所得的主要产物为单取代的BPB-Ni(II)-Ala复合物,双-α-甲基氨基酸复合物中间体收率分别为38%,36%,45%,经过水解后生成相应的双-α-甲基氨基酸,分别为2,7-二氨基-2,7-二甲基辛二酸、2,8-二氨基-2,8-二甲基壬二酸、2,9-二氨基-2,9-二甲基癸二酸.手性助剂2-N-(N'-苄基脯氨酰)-氨基二苯甲酮的回收率可高达95%.

Several bis（α-methylamino acid）s were synthesized by using alanine-Ni-2[N＇-（N-benzylprolyl）- amino]benzophenone [BPB-Ni（Ⅱ）-Ala] as chiral auxiliary with a,α-dibromoalkane. The substitution reaction with different carbon chain length of a,α-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（α-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（α-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.