Theoretical Mechanistic Investigation of the Dynamic Kinetic Resolution of N-Protected Amino Acid Esters using Phase-Transfer Catalysts
Theoretical Mechanistic Investigation of the Dynamic Kinetic Resolution of N-Protected Amino Acid Esters using Phase-Transfer Catalysts
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使用相转移催化剂动态动力学拆分 N-保护氨基酸酯的理论机理研究
DOI：
10.1021/acs.joc.2c02352
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Tokunaga Makoto
中科院分区：
文献类型：
--
作者：
Yamamoto Eiji;Kobayashi Kaoru;Wakafuji Kodai;Kamachi Takashi;Tokunaga Makoto
用相转移催化剂对N-保护氨基酸酯的动态动力学拆分进行了详细的理论机理研究。利用ConFinder程序和伪TS构象搜索(PTSCS)方法对类过渡态(TS)结构进行半自动穷举构象搜索。该构象搜索方法成功地为确定六氟异丙酯(HFIP)不对称碱解的立体选择性和消旋机理提供了合理的TS结构。此外，对TS结构的独立梯度模型分析表明，氢键与氧阴离子空穴的相互作用和π堆积作用是所提出的TS结构的共同重要特征，它们决定了立体选择性。
A detailed theoretical mechanistic investigation on the dynamic kinetic resolution of N-protected amino acid esters using phase-transfer catalysts is described. Semiautomatic exhaustive conformation search of transition state (TS)-like structures were carried out using the ConFinder program and the pseudo-TS conformational search (PTSCS) method. This conformational search method successfully provided reasonable TS structures for determining the stereoselectivity in the asymmetric base hydrolysis of hexafluoroisopropyl (HFIP) esters as well as the racemization mechanism. Furthermore, the independent gradient model (IGM) analysis of the TS structures suggested that the H-bonding interactions with the oxyanion hole and π-stacking interactions are the common important features of the proposed TS structures that determine the stereoselectivity.