Unveiling the Singular Conformation of the 3‐Fluoropyrrolidinium Cation

Abstract

AbstractThe pyrrolidine ring is a 5‐membered ring that holds significant importance in biological chemistry. The introduction of fluorine at position 3 of pyrrolidine results in pseudo‐axial and pseudo‐equatorial C−F bonds. However, both quantum‐chemical calculations and infrared spectroscopy reveal that the 3‐fluoropyrrolidinium cation only adopts one conformation, with the C−F bond in the pseudo‐axial orientation. Upon deprotonation of 3‐fluoropyrrolidinium, leading to the formation of 3‐fluoropyrrolidine, four conformations are predicted based on CCSD/DGTZVP quantum‐chemical calculations. Among these, the conformation favoring an N−H⋅⋅⋅F−C interaction emerges as the most stable, both in the gas phase and within an implicit DMSO medium. The heightened ring puckering observed in 3‐fluoropyrrolidinium compared to the most stable conformation of 3‐fluoropyrrolidine suggests that the singular conformation of the cation arises from a robust attractive electrostatic interaction resembling hydrogen bonding, rather than a charge‐dipole gauche effect as previously assumed.