Wen Wei, Chen Lei, Luo Ming-Jing, Zhang Yan, Chen Ying-Chun, Ouyang Qin, Guo Qi-Xiang
Key Laboratory of Applied Chemistry of Chongqing Municipality, School of Chemistry and Chemical Engineering , Southwest University , Chongqing 400715 , China.
College of Pharmacy , Third Military Medical University , Chongqing 400038 , China.
J Am Chem Soc. 2018 Aug 1;140(30):9774-9780. doi: 10.1021/jacs.8b06676. Epub 2018 Jul 20.
Chiral aldehyde catalysis is uniquely suitable for the direct asymmetric α-functionalization of N-unprotected amino acids, because aldehydes can reversibly form imines. However, there have been few successful reports of these transformations. In fact, only chiral aldehyde catalyzed aldol reactions of amino acids and alkylation of 2-amino malonates have been reported with good chiral induction. Here, we report a novel type of chiral aldehyde catalyst based on face control of the enolate intermediates. The resulting chiral aldehyde is the first efficient nonpyridoxal-dependent catalyst that can promote the direct asymmetric α-functionalization of N-unprotected glycine esters. Possible transition states and the proton transfer process were investigated by density functional theory calculations.
手性醛催化特别适用于N-未保护氨基酸的直接不对称α-官能团化反应，因为醛可以可逆地形成亚胺。然而，关于这些转化反应的成功报道很少。事实上，仅有手性醛催化氨基酸的羟醛反应以及2-氨基丙二酸酯的烷基化反应的手性诱导效果较好的报道。在此，我们报道了一种基于烯醇盐中间体的面控制的新型手性醛催化剂。所得的手性醛是第一种有效的非吡哆醛依赖性催化剂，它能够促进N-未保护甘氨酸酯的直接不对称α-官能团化反应。通过密度泛函理论计算研究了可能的过渡态和质子转移过程。
