Weak Functional Group Interactions Revealed Through Metal-Free Active Template Rotaxane Synthesis

Modest functional group interactions can play important roles in molecular recognition, catalysis and self-assembly. However, weakly associated binding motifs are often difficult to characterize. Here we report on the metal-free active template synthesis of [2]rotaxanes in one step, in up to 95 % yield with >100:1 rotaxane:axle selectivity, from primary amines, crown ethers and a range of C=O, C=S, S(=O)2 and P=O electrophiles. In addition to being a simple and effective route to a broad range of rotaxanes, the strategy enables 1:1 interactions of crown ethers with various functional groups to be characterized in solution and the solid state, several of which are too weak—or are disfavored compared to other binding modes—to be observed in typical host-guest complexes. The approach may be broadly applicable to the kinetic stabilization and characterization of other weak functional group interactions.