Enhanced Helical Folding of <i>ortho</i>-Phenylenes through the Control of Aromatic Stacking Interactions

Abstract

The <i>ortho</i>-phenylenes are a simple class of foldamers, with the formation of helices driven by offset aromatic stacking interactions parallel to the helical axis. For the majority of reported <i>o</i>-phenylene oligomers, the perfectly folded conformer comprises perhaps 50–75% of the total population. Given the hundreds or thousands of possible conformers for even short oligomers, this distribution represents a substantial bias toward the folded state. However, “next-generation” <i>o</i>-phenylenes with better folding properties are needed if these structures are to be exploited as functional units within more complex architectures. Here, we report several new series of <i>o</i>-phenylene oligomers, varying both the nature and orientation of the substituents on every repeat unit. The conformational behavior was probed using a combination of NMR spectroscopy, DFT calculations, and X-ray crystallography. We find that increasing the electron-withdrawing character of the substituents gives oligomers with substantially improved folding properties. With moderately electron-withdrawing groups (acetoxy), we observe >90% of the perfectly folded conformer, and stronger electron withdrawing groups (triflate, cyano) give oligomers for which misfolded states are undetectable by NMR. The folding of these oligomers is only weakly solvent-dependent. General guidelines for the assessment of <i>o</i>-phenylene folding by NMR and UV–vis spectroscopy are also discussed