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7940088 
Journal Article 
Fluorine-Induced Pseudo-Anomeric Effects in Methoxycyclohexanes through Electrostatic 1,3-Diaxial Interactions 
Piscelli, BA; Sanders, W; Yu, C; Al Maharik, N; Lebl, T; Cormanich, RA; O'Hagan, D 
2020 
Yes 
Chemistry: A European Journal
ISSN: 0947-6539
EISSN: 1521-3765 
26 
52 
11989-11994 
English 
32588927 
WOS:000560363700001 
We report counter-intuitive axial preferences in non-stereochemically biased, selectively fluorinated methoxycyclohexanes. These pseudo-anomeric effects are apparent when electronegative CF2 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. 
anomeric effects; computational chemistry; conformational analysis; fluorination; medicinal chemistry