Fluorine induced pseudo-anomeric effects in methoxycyclohexanes through electrostatic 1,3-diaxial interactions.

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 hydrogens electropositive. The electrostatic interaction between these axial hydrogens 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 o 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.