The contribution of non-classical CHaxOC hydrogen bonds to the anomeric effect in fluoro and oxa-methoxycyclohexanes

Abstract

In this theory study we demonstrate the dominance of non-classical 1,3-diaxial CH_axOC hydrogen bonds (NCHBs) dictating a 'pseudo' anomeric effect in selectively fluorinated methoxycyclohexanes and also influencing the axial preference in the classical anomeric exhibitor 2-methoxytetrahydropyran, a phenomenon which is most often described as a consequence of hyperconjugation. Analogues of methoxycyclohexane where ring CH₂'s are replaced by CF₂ can switch to an axial preference and theory methods (NBO, QTAIM, NCI) indicate the dominance of 1,3-CH_axOMe interactions over hyperconjugation. For 2-methoxytetrahydropyran, it is revealed that the global contribution to the anomeric effect is from electrostatic interactions including NCHBs, not hyperconjugation, although hyperconjugation (n_O→σ*_CO or n_O→σ*_CC) remains the main contributor to the exo-anomeric phenomenon. When two and three ether oxygens are introduced into the ring, then both the NCHB interactions and hyperconjugative contributions become weaker, not stronger as might have been anticipated, and the equatorial anomers progressively dominate.