Lewis acid-mediated nucleophilic substitution reactions of substituted tetrahydropyran acetates reveal that the conformational preferences of six-membered-ring cations depend significantly upon the electronic nature of the substituent. Nucleophilic substitutions of C-3 and C-4 alkyl-substituted tetrahydropyran acetates proceeded via pseudoequatorially substituted oxocarbenium ions, as would be expected by consideration of steric effects. Substitutions of C-3 and C-4 alkoxy-substituted tetrahydropyran acetates, however, proceeded via pseudoaxially oriented oxocarbenium ions. The unusual selectivities controlled by the alkoxy groups were demonstrated for a range of other heteroatom substituents, including nitrogen, fluorine, chlorine, and bromine. It is believed that the pseudoaxial conformation is preferred in the ground state of the cation because of an electrostatic attraction between the cationic carbon center of the oxocarbenium ion and the heteroatom substituent. This analysis is supported by the observation that selectivity diminishes down the halogen series, which is inconsistent with electron donation as might be expected during anchimeric assistance. The C-2 heteroatom-substituted systems gave moderately high 1,2-cis selectivity, while small alkyl substituents showed no selectivity. Only in the case of the tert-butyl group at C-2 was high 1,2-trans selectivity observed. These studies reinforce the idea that ground-state conformational effects need to be considered along with steric approach considerations.