Density Functional Theory Computational Reexamination of the Anomeric Effect in 2-Methoxy- and 2-Cyano-1,3-dioxanes and 1,3-Dithianes. Stereoelectronic Interactions Involving the Cyano (C≡N:) Group Revealed by Natural Bond Orbital (NBO) Analysis

This study reports DFT geometry optimization of the anancomeric (ring conformationally anchored) axial r2-methoxy-trans-4,trans-6-dimethyl- and r-2-cyano-trans-4,trans-6-dimethyl-1,3-dioxanes (1-ax and 3-ax, respectively), the equatorial isomers (2-eq and 4-eq, respectively), the axial r2-methoxy- and r2-cyano-trans-4,trans-6-dimethyl-1,3-dithianes (5-ax and 7-ax, respectively), and the equatorial isomers (6-eq and 8-eq, respectively). The computational results reproduce the anomeric effect in 1–8, and most importantly, Weinhold’s NBO analysis supports the contribution of n(X) → σ*(C–Y) stereoelectronic interactions that stabilize the axial isomers. Furthermore, NBO analysis of delocalization energy E(2) of properly aligned filled/empty orbitals in these isomeric 2-polar-substituted heterocycles reveals that n(O) → σ*(C–Hax) is responsible for the increased charge density at C(2)–Hax in the equatorial isomers, providing an explanation for the computational observation that very recently led Wiberg, Bailey...