Substitution reactions using carbon nucleophiles occur with high diastereoselectivity with cyclic acetals, hemiacetals, and carbohydrates. Limited selectivity has been observed with sterically bulky linear acetals, however, many attempts to apply neighboring-group participation or contact-ion pairing to substitution reactions of acyclic acetals have not afforded consistent selectivity results. We observed that neighboring-group participation by a nearby carbonyl group will form a rigid intermediate such as a <i>trans</i>-fused five-membered cyclic dioxolenium ion. This intermediate would then undergo an S<sub>N</sub>2-like substitution reaction at the acetal center to afford the product with high diastereoselectivity. Neighboring-group participation was confirmed by isolating dioxolane products resulting from nucleophilic addition into the dioxolenium ion intermediate. Using a pivaloate ester as the participating group and strong nucleophiles produced substitution products with diastereoselectivities higher than 90:10.

Diastereoselective nucleophilic substitution reactions of acyclic acetals

2019 Fall National Meeting

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