Neighboring-group participation of an ester enabled stereocontrol in substitution reactions of acyclic acetals. The ester group formed a trans-fused dioxolenium ion intermediate, which underwent a substitution reaction at the acetal carbon atom to afford the product with high diastereoselectivity. Neighboring-group participation was confirmed by isolating dioxolane products resulting from nucleophilic addition at C-2 of a 1,3-dioxolenium ion intermediate. Using a pivaloate ester as the participating group in combination with strong nucleophiles produced substitution products with diastereoselectivities of ≥90:10.