Divergent Chiral Self‐Sorting of Covalent Organic Pillars Switched by Subtle Conformational Preferences

Chiral self-sorting enables molecular systems to translate stereochemical information from small building blocks into highly organized architectures across length scales, echoing the hierarchical expression of chirality in biological systems. However, predicting whether a system will favor homochiral or heterochiral organization, let alone rationally controlling the sorting outcome, remains challenging. Here we show that the chiral self-sorting of covalent organic pillars (COPs) can be selectively switched through minimal structural variation in the linker units. Two diamine linkers, 2,6-bis(aminomethyl)pyridine and m-xylylenediamine, were used to connect pairs of stereolabile penta-aldehyde tiara[5]arene macrocycles through dynamic covalent [2+5] imine condensation. Despite their close resemblance, these linkers lead to divergent outcomes. Whereas 2,6-bis(aminomethyl)pyridine directs social chiral self-sorting to give a meso COP, m-xylylenediamine promotes narcissistic chiral self-sorting to afford enantiomeric COPs. In both cases, the products form cleanly without detectable stereoisomeric byproducts, and their stereochemical assignments are confirmed by X-ray crystallography. Computational analyses support the view that distinct linker conformational preferences provide a rationale for the divergent sorting pathways. This work establishes COPs as a model platform for understanding chiral self-sorting and provides a conceptual basis for selecting, amplifying, and expressing stereochemical information in complex molecular architectures.