Nucleophilic epoxidation is the formation of epoxides from electron-deficient double bonds through the action of nucleophilic oxidants. Nucleophilic epoxidation methods represent a viable alternative to electrophilic methods, many of which do not epoxidize electron-poor double bonds efficiently.
Although the most commonly used asymmetric epoxidation methods (the Sharpless-Katsuki, and Jacobsen epoxidations) rely on the catalytic reactivity of electrophilic oxidants, nucleophilic oxygen sources substituted with a suitable leaving group can also act as epoxidation reagents. The classic example, the Weitz-Scheffer reaction employs hydrogen peroxide under basic conditions (Z = OH below). Other notable examples have employed hypochlorites (Z = Cl) and chiral peroxides (Z = OR*).
Asymmetric versions of the above reaction have taken advantage of a number of strategies for achieving asymmetric induction. The highest yielding and most enantioselective methods include:
* Use of stoichiometric chiral oxidant
* Use of stoichiometric metal peroxides substituted with chiral ligands
* Use of stoichiometric chiral base
* Use of polypeptides
Although the mechanisms of each of these reactions differ somewhat, in each case the chiral catalyst or reagent must be involved in the [https://en.wiktionary.org/wiki/enantio- enantio] determining conjugate addition step. Cis-epoxides are difficult to access using nucleophilic epoxidation methods. Nearly all nucleophilic epoxidations of cis olefins afford trans epoxides.