Foldamers With Two Distinct Helical Motifs Controlled by Solvent

ABSTRACT

Abiotic foldamers that switch between distinct, well‐defined geometries are rare. Here, we report a structurally simple series of oligomers with alternating ortho ‐phenylene and 2,3‐pyrazinylene repeat units. Deconvolution of variable‐temperature ¹ H NMR spectra, with the help of ab initio chemical shift predictions, shows that the oligomers favor a compact, arene‐stacked helix in chloroform but a structurally distinct extended helix in acetone. The longest oligomer investigated, a heptamer, exhibits nearly perfect solvent‐switching behavior at low temperature, effectively doubling its length in acetone compared to chloroform. X‐ray crystallography confirms that the hybrid backbone is capable of both folding motifs. While arene–arene stacking drives folding in chloroform, nonclassical intramolecular C⁠─H⁠⋯⁠N hydrogen bonds appear to be more important in acetone. Both geometries are enthalpically favored in their respective solvents, highlighting how a balance of weak, competing interactions can be harnessed to achieve large‐scale geometry changes in synthetic foldamers.