Understanding the Conformational Behavior of Fluorinated Piperidines: The Origin of the Axial‐F Preference
Zackaria Nairoukh, Felix Strieth‐Kalthoff, Klaus Bergander, Frank Glorius
Abstract
Gaining an understanding of the conformational behavior of fluorinated compounds would allow for expansion of the current molecular design toolbox. In order to facilitate drug discovery efforts, a systematic survey of a series of diversely substituted and protected fluorinated piperidine derivatives has been carried out using NMR spectroscopy. Computational investigations reveal that, in addition to established delocalization forces such as charge-dipole interactions and hyperconjugation, solvation and solvent polarity play a major role. This work codifies a new design principle for conformationally rigid molecular scaffolds.
Topics & Concepts
ChemistrySolvationHyperconjugationComputational chemistryPiperidineDelocalized electronDipolePolarity (international relations)Drug discoveryChemical physicsStereochemistryMoleculeOrganic chemistryCellBiochemistryFluorine in Organic ChemistryOrganic and Inorganic Chemical ReactionsMolecular Spectroscopy and Structure