11.12: Acid-Catalyzed Ring-Opening of Epoxides
Epoxides that are three-membered ring systems are more reactive than other cyclic and acyclic ethers. The high reactivity of epoxides originates from the strain present in the ring. This ring strain acts as a driving force for epoxides to undergo ring-opening reactions either with halogen acids or weak nucleophiles in the presence of mild acid. The acid catalyst converts the epoxide oxygen, a poor leaving group, into an oxonium ion, a better leaving group, making the reaction feasible. The reaction follows the SN2 mechanism, and the protonated oxygen, unlike other leaving groups, does not detach from the molecule. The regiochemistry of the products formed is governed by either steric or electronic effects. In the case of an asymmetrical epoxide bearing a primary and a secondary carbon, the steric effect dominates and favors the nucleophilic attack at a less-hindered carbon. However, in epoxides where one of the carbons is tertiary, the electronic effect comes into play and favors the attack at a more-hindered carbon. The stereochemistry of the products is similar to an SN2 reaction, where the nucleophile attacks anti to the leaving group. Notably, the anti-attack at a chiral carbon causes an inversion of configuration.