Conformational equilibria involving 2-amino-1,3-dioxans: Steric control of the anomeric effect

Although N,N,1-trimethylcyclohexamine exists in two equilibrating conformations, with the NMe2 group axial and equatorial in comparable amounts, in N,N,2-trimethyl-2-amino-1,3-dioxane the conformation with the amine equatorial could not be detected; evidence for an anomeric effect for the NMe2 group of >3 kJ mol(-1). When the NMe2 group is axial in the dioxane, there can be no exo-anomeric effect (this would mean placing a methyl group over the ring), but the endo-anomeric effect is unaffected. Calculations show that when the NMe2 group is equatorial, the rotamer lowest in energy is one in which an exo-anomeric effect is possible, despite the steric demands involved. Thus the endo-anomeric effect in N,N,2-trimethyl-2-amino-1,3-dioxane is greater than the exo-anomeric effect, even though amine nitrogen is generally a better electron-pair donor than oxygen.