The Contribution of Hyperconjugation and Inductive Effects to the Pseudo-Anomeric Effect in 4-Substituted Methoxycyclohexanes

The importance of electrostatic non-conventional hydrogen bonds (NCHBs) to the pseudo-anomeric effect of 4-substituted methoxycyclohexanes is evaluated using theory (NBO) to deconvolute electrostatic from other contributing effects. There is an interesting interplay between σCH → σ*CX hyperconjugation and the electropositive charge on the 3,5-axial hydrogens (Hax). In essence better σ*CX (or 𝜋*CO) acceptors increase the charge on 3,5-CHax, which in turn strengthens Cδ⁺Hax···δ⁻OMe NCHB interactions.