The highest yielding and most enantioselective methods include: Although the mechanisms of each of these reactions differ somewhat, in each case the chiral catalyst or reagent must be involved in the enantio determining conjugate addition step.
The mechanism of nucleophilic epoxidation begins with conjugate addition of the peroxide (or other O-nucleophilic species) to the enone.
Attack of the enolate on the peroxide oxygen generates the epoxide product and releases a leaving group.
The evolution of ethane gas and uptake of oxygen are evidence for ligand exchange followed by oxidation of the intermediate zinc alkoxide species.
Simple tartrate and pseudoephedrine ligands are effective in combination with these metals; however, little detailed information about the precise mechanisms of these systems is known.
In combination with BINOL ligands and cumene hydroperoxide, lanthanide alkoxides can be used to epoxidize both trans and cis enones with high enantioselectivity.
This section describes asymmetric nucleophilic epoxidation methods, organizing them according to the constitution and configuration of the unsaturated substrate.
Lanthanide catalysts do effectively prevent bond rotation, however,[19] and provide access to cis epoxide products.
(10)With the lone exception of methylidene tetralone substrates,[10] no general methods are available for the asymmetric nucleophilic epoxidation of trisubstituted double bonds.
[22] (11)Epoxidations of other electron-deficient double bonds (substituted by electron-withdrawing groups other than carbonyls) are limited in scope, although a few examples have been reported.
[23][24] The ability of the carbonyl group to coordinate Lewis acidic functionality is critical for most existing methods.
[29] (13)Oxidation of epoxy alcohols generated via Sharpless epoxidation is a third method for the enantioselective synthesis of chiral α,β-epoxy carbonyl compounds.