Resolving Conformational Chirality in a Stereolabile Macrocycle

Conformational chirality is widespread in principle, yet often inaccessible in practice because rapid stereochemical averaging can preclude both enantiomeric resolution and chiroptical characterization. Here we show that a stereolabile pillar[5]arene-based macrocycle, though dynamically racemic in solution, undergoes spontaneous resolution upon crystallization to form a conglomerate. Single-crystal X-ray diffraction shows that individual crystals contain one of the two enantiomeric conformers, while solid-state electronic and vibrational circular dichroism, supported by density functional theory calculations, establish their absolute configurations. Notably, this handedness is also expressed in distinguishable hemihedral facets, enabling manual sorting by external morphology. The same conglomerate packing motif can be retained across related solvomorphs, while a chiral guest can bias crystallization toward a single-handed form. These results establish a direct link among molecular structure, solid-state chiroptical response, crystal morphology, and absolute configuration within a dynamically racemic system, and illustrate how crystallization can render otherwise averaged conformational chirality structurally, spectroscopically, and even visually legible.