Chemical Dynamic Thermodynamic Resolution and S/R Interconversion of Unprotected Unnatural Tailor-made α‑Amino Acids

Described here is an advanced, general method for purely chemical dynamic thermodynamic resolution and S/R interconversion of unprotected tailor-made α-amino acids (α-AAs) through intermediate formation of the corresponding nickel­(II)-chelated Schiff bases. The method features virtually complete stereochemical outcome, broad substrate generality (35 examples), and operationally convenient conditions allowing for large-scale preparation of the target α-AAs in enantiomerically pure form. Furthermore, the new type of nonracemizable axially chiral ligands can be quantitatively recycled and reused, rendering the whole process economically and synthetically attractive.

本文描述了一种先进的通用方法，可通过生成对应镍(II)螯合席夫碱（nickel­(II)-chelated Schiff base）中间体，实现未保护定制化α-氨基酸（α-amino acids，缩写α-AAs）的纯化学动态热力学拆分与S/R构型互变。该方法具备近乎完全的立体化学选择性结果、宽泛的底物适用范围（涵盖35个反应实例），且操作条件便捷，可实现对映纯形式目标α-氨基酸的大规模制备。此外，该新型不可消旋轴手性配体（axially chiral ligand）可被定量回收复用，使得整个过程在经济性与合成实用性层面均极具吸引力。