Non-natural, tailor-made amino acids are of crucial importance to the synthesis of bioactive peptides and new chemical entities. Innovative methodology is always needed for the preparation of enantiomerically pure amino acids that does not rely on tedious resolution procedures. We report here the multikilogram scale synthesis of the chiral nucleophilic glycine equivalent Ni(II) complexes (S)-19 and (R)-19 derived from (S)- and (R)-N-(2-benzoyl-4-chlorophenyl)-1-[(3,4-dichlorophenyl)methyl]-2-pyrrolidinecarboxamide. Replacement of the traditional carbonate bases with the soluble organic base DBU for synthesis resulted in improved process efficiency, safety, and yield. The issue of partial racemization of the proline moiety is critically addressed, and enantiomeric purities in excess of 99.5% ee are routinely achieved in this manufacture.

中文翻译：

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（S）-和（R）-N-（2-苄基-4-氯苯基）-1-[（3,4-二氯苯基）甲基]-衍生的甘氨酸席夫碱Ni（II）配合物的大规模合成2-吡咯烷羧酰胺

非天然，量身定制的氨基酸对于生物活性肽和新化学实体的合成至关重要。制备不依赖乏味拆分程序的对映体纯氨基酸始终需要创新的方法。我们在这里报告的手性亲核甘氨酸当量Ni（II）配合物（S）-19和（R）-19的多千克级合成，衍生自（S）-和（R）-N-（2-苯甲酰基-4-氯苯基）-1-[（（3,4-二氯苯基）甲基] -2-吡咯烷甲酰胺。用可溶的有机碱DBU代替传统的碳酸盐碱进行合成可提高工艺效率，安全性和产量。脯氨酸部分的部分外消旋化的问题得到了关键解决，在该制备中常规地获得超过99.5％ee的对映体纯度。