Stereodefined Improbable [3]Rotaxane by Post-Interlocking Ring Editing

The synthesis of higher-order mechanically interlocked molecules is challenging when targeting so-called improbable rotaxanes-statistically disfavored architectures whose ring and axle components lack mutual recognition. This challenge becomes more severe when the rings are racemic or stereolabile, as any successful assembly will inevitably produce a stereoisomeric mixture rather than a well-defined product. Herein, we demonstrate a post-interlocking ring editing strategy using covalent organic pillar COP-1 as the ring component. Nanotubular COP-1 is assembled by dynamic covalent imine condensation of two inherently chiral yet stereolabile macrocyclic building blocks that exhibit negligible binding towards long n-alkyl threads. Preorganization within COP-1 renders the duplex scaffold stereostable, enabling its chiral resolution and switching on ring-axle recognition. Using the resolved COP-1, a threading-followed-by-stoppering protocol furnishes enantiopure [2]rotaxanes. Subsequent imine hydrolysis edits the interlocked COP-1 duplex into its two parent macrocycles, converting each [2]rotaxane into the corresponding improbable [3]rotaxane. The mechanical bond preserves the stereochemical configuration inherited from COP-1, without loss of enantiopurity. This post-interlocking ring editing strategy circumvents the statistical limitations of direct multiring interlocking, providing a programmable route to stereodefined improbable rotaxanes and design principles for higher-order chiral mechanically interlocked architectures.