Abstract
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 (19F{1H}‐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.
Highlights
We report counter-intuitive axial preferences in non-stereochemically biased, selectively fluorinated methoxycyclohexanes
A ‘double bond/no bond’ analysis emerged a decade later which was in line with bond lengths emerging from crystallography and theory.[6]. This argued, for example, that in pyran 1ax, hyperconjugative interactions between a lone pair of the ring oxygen and the s*CÀO antibonding orbital of the methoxyl group stabilises 1ax
Takahashi et al.,[10,11] have recognised the importance of coloumbic/electrostatic 1,3-diaxial CH···n(lone pair) interactions stabilising 1ax and the axial conformers of 1,3-dioxolanes such as 2ax, and have argued that such effects contribute to anomeric stabilisation in carbohydrates too
Summary
We report counter-intuitive axial preferences in non-stereochemically biased, selectively fluorinated methoxycyclohexanes. A ‘double bond/no bond’ analysis emerged a decade later which was in line with bond lengths emerging from crystallography and theory.[6] This argued, for example, that in pyran 1ax, hyperconjugative interactions between a lone pair of the ring oxygen and the s*CÀO antibonding orbital of the methoxyl group (endo anomeric effect) stabilises 1ax.
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