Scheme 9.1 The Weitz-Scheffer epoxidation.
alkenes requires the formation of nucleophilic oxidative species. The first example of the epoxidation of α,β-unsaturated carbonyl compounds was reported by Weitz and Scheffer in 1921 (Scheme 9.1) [16].
This two-step process first involves the conjugate addition to the α,β-unsaturated ketone 1 of the hydroperoxide anion generated after deprotonation of hydrogen peroxide in an alkaline medium. The anionic intermediate then gives rise to the epoxy ketone 2 by ring closure. Although control of the alkene geometry can, in principle, be problematic, highly diastereoselective and enantioselective epoxidation reactions of electron-poor alkenes have been developed. The metal-based and organocatalyzed methodologies for the asymmetric epoxidation of α,β-unsaturated carbonyl compounds reported over the past two decades will be described in this chapter. Illustrations of the scope and limitations, mechanistic aspects and -whenever possible -the applications of different systems, will be included in an attempt to provide an update for both academic and industrial chemists. 9.2 Metal-Catalyzed Epoxidations 9.2.1 Epoxidation of α,β-Unsaturated Ketones Mediated by Chirally Modified Zn-and Mg-Alkyl Peroxides