Inverted metal-free active template synthesis of rotaxanes via axle‑mediated macrocyclization

Rotaxane synthesis generally requires the macrocycle to contain recognition sites for the threaded axle or its building blocks. Here we show that flexible oligo(ethylene glycol) axles can instead promote the formation of macrocycles around themselves, enabling an inverted, metal-free active-template route to rotaxanes from simple building blocks. The axle accelerates amide-bond-forming macrocyclization through hydrogen bonding, giving [2]rotaxanes in up to 70% yield. Longer axles enable the iterative assembly of higher-order [n]rotaxanes, with up to four macrocycles threaded onto an octa(ethylene glycol) chain. The X-ray crystal structure of such a [5]rotaxane reveals a crowded helical stack of rings stabilized by aromatic stacking and hydrogen bonding, explaining the enhanced efficacy of the later macrocyclizations. Subsequent deletion of the newly formed amides gives structurally minimalist rotaxanes comprising an oligo(ethylene glycol) axle threaded through a cyclohydrocarbon. Removing the requirement for particular functional groups and structural motifs in rotaxane macrocycles increases the accessible structures of mechanically interlocked molecules.