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Understanding the Conformational Behavior of Fluorinated Piperidines: The Origin of the Axial‐F Preference
Author(s) -
Nairoukh Zackaria,
StriethKalthoff Felix,
Bergander Klaus,
Glorius Frank
Publication year - 2020
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.202001355
Subject(s) - chemistry , solvation , hyperconjugation , computational chemistry , piperidine , delocalized electron , dipole , polarity (international relations) , drug discovery , chemical physics , stereochemistry , molecule , organic chemistry , biochemistry , cell
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.