英国杜伦大学Kitching, Matthew O.团队报道了铵离子的对映选择性合成。相关研究成果发表在2021年9月1日出版的《自然》。

控制分子的手性是有机合成中的一个基本挑战。尽管对映选择性地构建碳立体中心的方法已经很成熟，但合成富集的杂原子立体中心的路线却很少受到关注。在有机分子中普遍存在的原子中，氮是最难进行立体化学控制的。虽然已经证明了有限数量的拆分过程，但未发现对映选择性制备氮立体中心的通用方法。

该文中，研究人员表明通过超分子识别过程很容易控制铵离子的手性。通过将1,1′-联-2-萘酚支架介导的对映选择性铵识别与允许氮立体中心外消旋化的条件相结合，可以以优异的产率和选择性产生手性铵阳离子。机理研究表明，通过溶液和固相识别的结合，热力学驱动的加成结晶过程负责观察到的选择性。

与基于动态和动力学分辨率的过程不同，动态和动力学分辨率受动力学控制，其允许通过自校正过程随时间增加选择性。氮立体中心的重要性可以通过立体选择性超分子识别来揭示，这在天然存在的伪对映体金鸡纳生物碱中是不可能的。随着铵离子对映体形式的实际获得，这个以前被忽视的立体中心现在可以被探索。

附：英文原文

Title: Enantioselective synthesis of ammonium cations

Author: Walsh, Mark P., Phelps, Joseph M., Lennon, Marc E., Yufit, Dmitry S., Kitching, Matthew O.

Issue&Volume: 2021-09-01

Abstract: Control of molecular chirality is a fundamental challenge in organic synthesis. Whereas methods to construct carbon stereocentres enantioselectively are well established, routes to synthesize enriched heteroatomic stereocentres have garnered less attention1,2,3,4,5. Of those atoms commonly present in organic molecules, nitrogen is the most difficult to control stereochemically. Although a limited number of resolution processes have been demonstrated6,7,8, no general methodology exists to enantioselectively prepare a nitrogen stereocentre. Here we show that control of the chirality of ammonium cations is easily achieved through a supramolecular recognition process. By combining enantioselective ammonium recognition mediated by 1,1′-bi-2-naphthol scaffolds with conditions that allow the nitrogen stereocentre to racemize, chiral ammonium cations can be produced in excellent yields and selectivities. Mechanistic investigations demonstrate that, through a combination of solution and solid-phase recognition, a thermodynamically driven adductive crystallization process is responsible for the observed selectivity. Distinct from processes based on dynamic and kinetic resolution, which are under kinetic control, this allows for increased selectivity over time by a self-corrective process. The importance of nitrogen stereocentres can be revealed through a stereoselective supramolecular recognition, which is not possible with naturally occurring pseudoenantiomeric Cinchona alkaloids. With practical access to the enantiomeric forms of ammonium cations, this previously ignored stereocentre is now available to be explored.

DOI: 10.1038/s41586-021-03735-5

Source: https://www.nature.com/articles/s41586-021-03735-5