Stereoselective Synthesis of Mechanically Planar Chiral Rotaxanes and Mechanical Geometric Isomers From a Macrocyclic...

Rotaxanes, a classical class of mechanically interlocked molecules (MIMs), can exhibit unique mechanical stereochemistry even when their individual components are stereochemically trivial, as exemplified by mechanically planar chiral (MPC) and mechanical geometric isomer (MGI) rotaxanes. However, the facile and stereoselective synthesis of these intriguing rotaxane stereoisomers remains challenging, particularly through catalytic enantioselective methods. We herein describe the design of a macrocyclic ketone-based prochiral rotaxane and the development of stereoselective methods to access both the MPC and MGI rotaxane stereoisomers from this common molecular platform. Specifically, an organocatalyzed asymmetric condensation between arylhydroxylamines and this prochiral rotaxane was developed to break overall molecular symmetry, affording the oxime ether-containing MPC rotaxanes with good to high enantioselectivities. Extensive control experiments were conducted to elucidate the origin of enantioselectivity in this system. Furthermore, the oxime ether-containing MPC rotaxanes underwent a two-step Beckmann rearrangement to provide novel MPC rotaxanes with lactam-containing macrocycles, with their enantiopurity largely retained. On the other hand, by tuning the reduction conditions applied to the same macrocyclic ketone-based rotaxane, we achieved the diastereoselective reduction of the carbonyl group, which led to the formation of both mechanical geometric isomers of Schill-type type 1 MGI rotaxanes, which have been relatively less explored to date.