Stereodivergent Macrocyclization in Dynamic Chiral Confinement

The absolute and relative configurations of a macrocyclic natural product bearing multiple chirality have a crucial influence on its physical and biological properties. Nevertheless, their preparation with full stereocontrol remains largely unexplored in synthetic community. Here, we show a stereodivergent macrocyclization under dynamic chiral confinement in which the stepwise chirality switching of a chiral space directs complete stereocontrol. To confine a substrate in a dynamic chiral space, we used a chiral capsule enclosing a substrate which is collectively switchable in the chirality in response to external stimuli, but their conformations are firmly fixed by subsequent self-assembly. The consecutive chirality switching enables the confined reactions of an enclosed achiral substrate to sequentially install diverse chirality on a macrocycle product with full stereocontrol in a single pot operation, thus changing only a sequence of physical stimuli enables access to a remarkable stereodivergence in a macrocyclization process.