Probing the Anomeric Effect. Trimethylsilyloxy and tert-Butoxy Substituents in 1,4-Dioxane Derivatives: Theory vs. Experiment¹

A conformational analytical study of a series of trimethylsilyloxy- (TMSO) and tert-butoxy- (TBO) substituted 1,4-dioxanes was performed using NMR techniques. It was found that the TMSO and TBO groups (in contrast to MeO, AcO, and PhO substituents²) alleviate the anomeric effect. Arguments based on molecular mechanics (MM2-parametrized for the anomeric effect) and MO ab initio calculations of ROCOR/ (R = CH₃, H; R' = SiH₃) at various levels help rationalize this behavior, by isolating and identifying steric and electronic contributions. The electronic factors are (i) strong attractive nonbonded OSi…-0 interactions within the R-O-C-O-Si system, which reduce considerably the O-C-O-Si dihedral angle (down to 0°) and the energy of the “ag” (equatorial) form vs. the “g⁺g⁺” one and (ii) inductive electron donation by SiMe₃(or CMe₃) which lowers the electronegativity of TMSO (or TBO). Steric factors and (p →d)π bonding are negligible. A single-crystal X-ray analysis of 2,5-di-tert-butoxy-l,4-dioxane revealed structural data in line with all the above.