Beyond Passive Substituents: Tosyl-Directed Self-Templation Enables Selective Pillar[4 + 1]arene Formation and...

Substituents in supramolecular chemistry are usually treated as passive handles that tune solubility or reactivity rather than as active determinants of assembly pathways. Here we show that tosyl groups promote directional noncovalent recognition and thereby control both cocyclization selectivity and postassembly topology in pillararenes. Under otherwise identical conditions, brominated analogues give statistical mixtures in which the pillar[4 + 1]arene product appears at only 1-19% distribution, whereas tosyl-substituted monomers undergo pseudorotaxane-like preassembly that enables highly selective self-templated pillar[4 + 1]arene formation without added external templates. A crystallographic survey of 12 single-crystal structures (N = 12), together with VT NMR, SAXS, molecular dynamics (MD) simulations, and fragment molecular orbital (FMO) analysis, establishes a valency-topology relationship in which increasing tosyl valency drives a progression from discrete monomers to interpenetrated dimers and higher-order aggregates. This substituent-dependent behavior extends across a broader alkoxy series, indicating that the effect is not limited to a single monomer pair. Upon benzoquinone oxidation, the tosyl-containing copillar[4 + 1]arene undergoes temperature-dependent switching between interpenetrated and self-included states, accompanied by changes in aggregation, a charge-transfer spectral shift, and reversible thermochromism quantifiable by ultraviolet-visible (UV-vis) spectroscopy and smartphone colorimetry. These findings establish substituent identity as an active design parameter for constructing reconfigurable and functionally responsive macrocyclic systems.