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 attention^1,2,3,4,5. 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 demonstrated^6,7,8, 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.

分子手性的控制是有机合成中的一个基本挑战。虽然对映选择性构建碳立体中心的方法已经确立，但合成富集杂原子立体中心的途径却很少受到关注^1,2,3,4,5。在有机分子中通常存在的那些原子中，氮是最难在立体化学上控制的。尽管已经证明了数量有限的解决过程^6,7,8，不存在对映选择性制备氮立体中心的通用方法。在这里，我们表明通过超分子识别过程很容易实现对铵阳离子手性的控制。通过将由 1,1'-bi-2-naphthol 支架介导的对映选择性铵识别与允许氮立体中心外消旋的条件相结合，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，热力学驱动的加合结晶过程是观察到的选择性的原因。与基于动态和动力学分辨率的过程不同，这些过程在动力学控制下，这允许通过自校正过程随时间增加选择性。金鸡纳生物碱。随着对铵阳离子的对映体形式的实际访问，这个以前被忽视的立体中心现在可以被探索。