Chiral macrocycles are commonly found in nature and have strong binding affinity to their targets. Thus, the development of efficient macrocyclization strategies is an important goal in the synthetic community. However, macrocyclization with chirality induction remains a great challenge because of the large entropic penalty associated with ring closure while maintaining the chiral conformation. Here, we report a highly efficient chiral macrocyclization with controlling enantioselectivity using a chiral confinement strategy. A linear substrate is encapsulated by a host precursor molecule through the formation of chiral capsule structures, which subsequently self-assemble into a robust two-dimensional structure entrapping the substrate with a folded chiral conformation. Then, the reaction under confinement generates an enantiopure macrocycle product. Furthermore, the chirality of the capsule assembly can switch into an opposite form using sonication, capable of controlling enantioselectivity. The substrate-encapsulating process is amenable to a substrate change, thus enabling diverse chirality induction in macrocycle formation. This macrocyclization method works with substrates decorated with a wide range of functional groups at high levels of precision and efficiency.

手性大环化合物在自然界中常见，对其靶标具有很强的结合亲和力。因此，开发有效的大环化策略是合成界的一个重要目标。然而，手性诱导的大环化仍然是一个巨大的挑战，因为在保持手性构象的同时与闭环相关的大熵损失。在这里，我们报告了使用手性限制策略控制对映选择性的高效手性大环化。线性基质通过形成手性胶囊结构被主体前体分子封装，随后自组装成坚固的二维结构，以折叠的手性构象捕获基质。然后，限制下的反应生成对映体纯大环产物。此外，胶囊组件的手性可以使用超声处理转变为相反的形式，能够控制对映选择性。底物封装过程适合底物变化，从而在大环形成中实现不同的手性诱导。这种大环化方法适用于装饰有多种官能团的基材，具有高精度和高效率。