11.13: Base-Catalyzed Ring-Opening of Epoxides
Due to their highly strained structures, epoxides can readily undergo ring-opening reactions through nucleophilic substitution, either in the presence of an acid or a base. The nucleophilic substitution reactions in the presence of acid are called acid-catalyzed ring-opening reactions, and nucleophilic substitution reactions in the presence of a base are called base-catalyzed ring-opening reactions. Epoxides undergo base-catalyzed ring-opening reactions in the presence of a strong nucleophile or a base. A variety of nucleophiles like sodium hydroxide, sodium alkoxide, sodium hydrosulfide, sodium cyanide, lithium aluminum hydride, and Grignard reagent can open the epoxide ring. The nucleophilic attack on the epoxide ring proceeds via an SN2 mechanism and involves an alkoxide intermediate. The product formed in base-catalyzed reactions shows SN2-like stereoselectivity and regioselectivity. The nucleophile attacks at the less-hindered carbon and anti to the leaving group, leading to the inversion of configuration at a chiral center. In contrast to epoxides, acyclic ethers do not undergo direct nucleophilic substitutions, as the reaction is thermodynamically unfavorable.