In an epoxide ring opening under acidic conditions, which carbon is attacked?

• A. The more substituted carbon.
• B. The less substituted carbon.
• C. The carbon adjacent to the oxygen.
• D. It opens randomly.

Answer: (A)

Under acidic conditions, the epoxide oxygen is protonated to give an oxonium ion, which makes the ring more electrophilic. The developing positive charge is best stabilized on the more substituted carbon, so that carbon bears more carbocation-like character in the transition state. A nucleophile therefore attacks that more substituted carbon, opening the ring and attaching the nucleophile to that carbon. If the substrate is chiral, the attack occurs from the backside at that carbon, resulting in inversion at that center. Under basic conditions, the nucleophile would prefer the less substituted carbon due to an SN2 pathway, but with acid catalysis the regiochemistry favors the more substituted carbon.