Shi Asymmetric Epoxidation

There had been many previous attempts to create an efficient non-metal catalyst for asymmetric epoxidations. In 1996, Yian Shi of Colorado State University developed a fructose-derived ketone catalyst that demonstrated excellent enantioselectivity. Since this discovery, the use of Shi’s catalyst has become known as the Shi asymmetric epoxidation.

The Shi epoxidation involves treating alkenes with oxone (potassium peroxymonosulfate) in the presence of the Shi catalyst. The reaction is believed to proceed via a dioxirane intermediate generated from the ketone catalyst by the oxone. One potential side reaction that can occur is the Baeyer-Villiger oxidation, where rearrangement of the peroxy group results in the formation of an ester. However, this can be mitigated by maintaining the pH at an optimum value of approximately 10.5.

The Shi epoxidation has been used in the key step of several total synthesis campaigns, including the synthesis of glabrescol, a chiral C2-symmetric pentacyclic oxasqualenoid, by Elias J. Corey and colleagues.