Electrostatic CH-π Interactions Can Override Fluorine Gauche Effects To Exert Conformational Control

Fluorine gauche effects are conformational properties of 2-fluoroethanes often applied in modern molecular designs. However, the physical origins of fluorine gauche effects are not well understood, with the consensus favoring the established hyperconjugation theory over an emerging electrostatic model. Using a series of model systems, we show that a shift to fluorine gauche effects can be influenced by intramolecular CH center dot center dot center dot pi aromatic interactions, a through-space event. Modulating the pi-ring (forming the aromatic interaction) with substituent groups resulted in a linear Hammett relationship, thus indicating that the CH center dot center dot center dot pi interaction has electrostatic features. For instance, attaching a nitro group (an electron-withdrawing substituent) to the pi-ring weakened the CH center dot center dot center dot pi interaction and led to a gauche preference, whereas an anti conformer is preferred with amine as substituent. The experimental results performed by using proton NMR spectroscopy are corroborated by gas-phase DFT calculations and solid-state X-ray crystallography.

Automated summary

This study investigates the physical origins of fluorine gauche effects and reveals that the intramolecular CH center dot center dot center dot pi aromatic interactions play a significant role in inducing these effects. The experimental results demonstrate that the CH center dot center dot center dot pi interaction has electrostatic features.