上海交通大学张万斌课题组在有机合成研究中取得进展。他们开发了一种镍/铜共催化的醛亚胺酯的不对称苄基化反应，用于对映选择性合成α-季碳氨基酸。2022年3月23日出版的《德国应用化学》杂志发表了这项成果。

在该研究中，课题组报道了首个不对称Ni/Cu共催化醛亚胺酯的苄基化反应。利用该反应，团队合成了一系列苄基取代的α-季碳氨基酸，并具有高收率和高对映选择性（收率达90%，ee值99%）。实验和理论计算结果表明，η3-苄基镍中间体的强亲电性是使反应在无碱条件下进行的关键。

在进一步研究中，团队应用该方法合成了细胞黏附抑制剂BIRT-377类似物，以及NK1受体拮抗剂PD154075和CCK-B受体拮抗剂CI-988的关键中间体。

附：英文原文

Title: Nickel/Copper-Cocatalyzed Asymmetric Benzylation of Aldimine Esters for the Enantioselective Synthesis of α-Quaternary Amino Acids

Author: Wanbin Zhang, Youbin Peng, Chongyu Han, Yicong Luo, Guanlin Li, Xiaohong Huo

Issue&Volume: 2022-03-23

Abstract: The first asymmetric Ni/Cu cocatalyzed benzylation of aldimine esters is reported. A series of benzyl substituted α-quaternary amino acids could be synthesized in high yield and with high levels of enantioselectivity (up to 90% yield and 99% ee). The experimental and theoretical calculation results suggested that the strong electrophilicity of the  η3-benzylnickel intermediate is crucial for the high reactivity, enabling the reaction under base-free conditions. Furthermore, this method has been applied to the synthesis of the cell adhesion inhibitor BIRT-377 analogues, and the key intermediate of NK1 receptor antagonist PD154075 and CCK-B receptor antagonist CI-988.

DOI: 10.1002/anie.202203448

Source: https://onlinelibrary.wiley.com/doi/10.1002/anie.202203448