A General and Scalable Chiral Surrogate Rotaxane Strategy for Highly Enantioenriched Mechanically Planar Chiral Rotaxanes

Abstract

ABSTRACT We report a general and modular chiral surrogate rotaxane (CSR) strategy for the synthesis of mechanically planar chiral rotaxanes (MPCRs) of high optical purity ( ca . 99.6% ee). A diastereomeric CSR, readily separable by column chromatography, is first generated through an S N 2 interlocking process in which a Na + ‐templated directional macrocycle encircling a chiral nucleophilic auxiliary is captured by a semidumbbell‐shaped electrophile. Subsequent displacement of the auxiliary with a semidumbbell‐shaped nucleophile furnishes the target MPCR with complete stereochemical fidelity and quantitative recovery of the auxiliary. This scalable approach avoids reliance on preparative chiral stationary phase HPLC and supports stereochemical assignment by correlation, reducing the need for product‐by‐product x‐ray crystallographic analysis. Moreover, the strategy provided access to all three stereoisomers of a co‐conformationally mechanically planar chiral [3]rotaxane, each in 99.8% stereoisomeric purity. These results establish a practical platform for accessing stereochemically well defined mechanically chiral rotaxanes for systematic study and future functional applications.