Dioxirane epoxidations, electrophilic reactivities

A high catalyst loading (typically 20-30 mol%) is usually required for the epoxidation with ketone 26 because Baeyer-Vilhger oxidation presumably decomposes the catalyst during the epoxidation. The fused ketal moiety in ketone 26 was replaced by a more electron-withdrawing oxazohdinone (32) and acetates (33) with the anticipation that these replacements would decrease the amount of decomposition via Baeyer-Villiger oxidation (Fig. 8) [71, 72]. Only 5 mol% (1 mol% in some cases) of ketone 32 was needed to get comparable reactivity and enantioselectivity with 20-30 mol% of ketone 26 [71]. Since dioxiranes are electrophilic reagents, they show low reactivity toward electron-deficient olefins, such as a, 3-unsaturated esters. Ketone 33, readily available from ketone 26, was found to be an effective catalyst towards the epoxidation of a, 3-unsaturated esters [72]. 

Electron-rich alkenes are the more reactive jr-bond snbstrates towards epoxidation by the electrophilic dioxiranes Some typical examples of these oxidations are snm-marized in Scheme 2. Since the resnlting epoxides are nsnally hydrolytically and ther-molytically qnite labile, snch oxidations are best carried ont with isolated dioxiranes. For example, the 8,9 epoxide of the well-known aflatoxin B, postnlated as potent carcinogen in the oxidative metabolism of this natural product, escaped numerous efforts to prepare it by conventional epoxidations because of its sensitivity towards hydrolysis . The synthesis of this labile epoxide was readily accomplished by employing a solution of the isolated DMD at room temperature (equation 2), and its mutagenicity unequivocally... 

The chemical reactivity most associated with dioxiranes is the electrophilic transfer of oxygen to electron-rich substrates (e.g., epoxidation, N-oxidation) as well as oxygen insertion reactions into unactivated C-H bonds. The reactivity-selectivity relationships among these types of reactions has been examined in depth by Curci. The reaction kinetics are dependent upon a variety of factors, including electron-donor power of the substrate, electrophilicity of the dioxirane, and steric influences (95PAC811]. 

The chemoselectivity of the dioxirane oxyfunctionalization usually follows the reactivity sequence heteroatom (lone-pair electrons) oxidation > JT-bond epoxida-tion > C-H insertion, as expected of an electrophilic oxidant. Because of this chemoselectivity order, heteroatoms in a substrate will be selectively oxidized in the presence of C-H bonds and even C-C double bonds. In allylic alcohols, however, C-H oxidation of the allylic C-H bond to a,/ -unsaturated ketones may compete efficaciously with epoxidation, especially when steric factors hinder the dioxirane attack on the Jt bond. To circumvent the preferred heteroatom oxidation and thereby alter the chemoselectivity order in favor of the C-H insertion, tedious protection methodology must be used. For example, amines may be protected in the form of amides [46], ammonium salts [50], or BF3 complexes [51] however, much work must still be expended on the development of effective procedures which avoid the oxidation of heteroatoms and C-C multiple bonds. 

Ketones other than acetone can be used for the formation of dioxiranes. Methyl(trilluoromethyl)dioxirane, formed from KHSO5 and the more electrophilic ketone trilluoroacetone, is a reactive dioxirane. This reagent can be used for the epoxidation of electron-poor a,p-unsaturated carbonyl compounds. Trifluoroace-tone can be used as a catalyst in combination with, for example, hydrogen peroxide... 

Ketone 25 has shown to provide high ee s and good yields for epoxidation of a number of electron-deficient a,p-unsaturated esters, whereas ketone 2 epoxidizes a,P-unsaturated esters sluggishly due to the low reactivity of its dioxirane as an electrophilic reagent toward electron-deficient olefins. 

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