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Fluorine‐Induced Pseudo ‐Anomeric Effects in Methoxycyclohexanes through Electrostatic 1,3‐Diaxial Interactions
Author(s) -
Piscelli Bruno A.,
Sanders William,
Yu Cihang,
Al Maharik Nawaf,
Lebl Thomas,
Cormanich Rodrigo A.,
O'Hagan David
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.202003058
Subject(s) - anomeric effect , natural bond orbital , fluorine , chemistry , cyclohexane , anomer , ring (chemistry) , computational chemistry , ab initio , electrostatics , hydrogen , hydrogen bond , ab initio quantum chemistry methods , crystallography , stereochemistry , organic chemistry , density functional theory , molecule
We report counter‐intuitive axial preferences in non‐stereochemically biased, selectively fluorinated methoxycyclohexanes. These pseudo‐anomeric effects are apparent when electronegative CF 2 groups are placed at the C‐2, C‐4 and C‐6 positions of the cyclohexane ring to render the C‐3/5 axial hydrogen atoms electropositive. The electrostatic interaction between these axial hydrogen atoms and the ‐OMe oxygen is stabilising. The effect is explored using high‐level ab initio and DFT calculations in the framework of NBO, QTAIM and NCI analysis across a range of derivatives, and experimentally ( 19 F{ 1 H}‐NMR at −80 °C) for some illustrative examples. The effect is significant in energy terms for a weak interaction, and illustrates a new stereoelectronic aspect attributed to selective fluorine substitution in organic chemistry.