Diastereoselective Rotaxane Synthesis with Pillar[5]arenes via Co-crystallization and Solid-State Mechanochemical Processes.

Chiral rotaxanes have attracted much attention in recent decades for their unique chirality based on their interlocked structures. Thus, selective synthesis methods of chiral rotaxanes have been developed. The introduction of substituents with chiral centers to produce diastereomers is a powerful strategy for the construction of chiral rotaxanes. However, in case of a small energy difference between the diastereomers, diastereoselective synthesis is extremely difficult. Herein, we report a new diastereoselective rotaxane synthesis method using solid-phase diastereoselective [3]pseudorotaxane formation and mechanochemical solid-phase end-capping reactions of the [3]pseudorotaxanes. By co-crystallization of stereodynamic planar chiral pillar[5]arene with stereogenic carbons at both rims and axles with suitable end groups and lengths, the [3]pseudorotaxane with a high diastereomeric excess (ca. 92% de) was generated in the solid state because of higher effective molarity with aid by packing effects and significant energy differences between [3]pseudorotaxane diastereomers. In contrast, the de of the pillar[5]arene was low in solution (ca. 10% de) because of a small energy difference between diastereomers. Subsequent end-capping reactions of the polycrystalline [3]pseudorotaxane with high de in solvent-free conditions successfully yielded rotaxanes while maintaining the high de generated by the co-crystallization.