近日，德国马克斯·普朗克研究所Benjamin List团队研究了一种非环N-叔胺的不对称合成。相关论文于2025年11月19日发表在《自然》杂志上。

化学与生物学中的大多数分子都具有手性，从而产生镜像变异体——即所谓的对映异构体。然而，尽管由碳原子产生立体中心的选择性化学合成方法已相当成熟，但氮手性分子的对映选择性合成路径却远为罕见；尤其对于无环氮手性胺类化合物，由于其快速的锥形翻转特性，相关合成方法更是难以实现。

研究组通过烯醇硅醚与硝鎓离子的加成反应，实现了稳定无环氮手性胺的催化不对称合成，该反应中硝鎓离子与受限手性阴离子形成离子对。在所制备的所谓异头胺中，两个氮-氧取代基有效阻碍了氮翻转，从而显著减缓了通常观察到的异构化现象。该关键立体生成步骤对以往确立的对映区分立体化学描述符提出了挑战。计算化学研究为观测到的立体控制来源提供了进一步阐释。该工作为探索具有光学纯度的异头胺这一迷人且尚未被充分开发的化学领域开辟了新途径。

附：英文原文

Title: The Asymmetric Synthesis of an Acyclic N-Stereogenic Amine

Author: Zhu, Chendan, Das, Sayantani, Sterling, Marie Sophie, Tsuji, Nobuya, Lger, Spencer J., Neese, Frank, De, Chandra Kanta, List, Benjamin

Issue&Volume: 2025-11-19

Abstract: Most molecules of chemistry and biology are chiral, leading to mirror image variants, so called enantiomers. However, while the selective chemical synthesis of molecules where the stereogenicity arises from a carbon atom is well-established, enantioselective approaches to nitrogen-stereogenic molecules are much less common,1-3 and in case of acyclic, N-stereogenic amines, even elusive, due to their rapid pyramidal inversion. We describe here the catalytic asymmetric synthesis of stable, acyclic N-stereogenic amines by the addition of enol silanes to nitronium ions that ion pair to a confined chiral anion. In the produced so-called anomeric amines, the commonly observed isomerization is slowed down by two N-oxy-substituents, which hamper nitrogen inversion. The critical stereogenicity creating step challenges previously established stereochemical descriptors of enantiodifferentiation. Computational studies provide additional insight into the origin of the observed stereocontrol. Our work opens up a new avenue to investigate the fascinating and previously underexplored chemistry of enantiopure anomeric amines.

DOI: 10.1038/s41586-025-09905-z

Source: https://www.nature.com/articles/s41586-025-09905-z