Epoxide-hydroperoxides, nucleophilic

Double bonds in a,/3-unsaturated keto steroids can be selectively oxidized with alkaline hydrogen peroxide to yield epoxy ketones. In contrast to the electrophilic addition mechanism of peracids, the mechanism of alkaline epoxidation involves nucleophilic attack of hydroperoxide ion on the con-... 

Acid-catalyzed intramolecular attack of nucleophilic hydroperoxide function on an oxirane ring results in formation of 3-(l-hydroxyalkyl)endoperoxides. For example, epoxidation of unsaturated hydroperoxide 320 affords oxirane-hydroperoxide 321 (66%), which through acid-catalyzed regioselective cyclization gives 1,2-dioxolane 322 (70%) (Scheme 79) . This type of reaction is applicable also to a more complex epoxide-hydroperoxide such as 323, which cyclizes to polyfunctionalized 5-membered cyclic... 

The reaction between alkyl hydroperoxides and enones has also been carried out using the same catalyst 28c and showing a similar behavior (Scheme 3.31). While the reaction usually leads to the formation of an epoxide as final product, under the optimized conditions and, in particular, by the correct election of the alkyl hydroperoxide nucleophile, the reaction can be directed to the formation of the p-peroxy-substituted ketone product in excellent yields and enantioselectivities. Reduction of these adducts allowed the preparation of the corresponding p-hydroxy ketone, therefore showing that the methodology is suitable for carrying out the formal enantioselective conjugate addition of OH to enones. 

Electron deficient carbon-carbon double bonds are resistant to attack by the electrophilic reagents of Section 5.05.4.2.2(t), and are usually converted to oxiranes by nucleophilic oxidants. The most widely used of these is the hydroperoxide ion (Scheme 79). Since epoxidation by hydroperoxide ion proceeds through an intermediate ct-carbonyl anion, the reaction of acyclic alkenes is not necessarily stereospecific (Scheme 80) (unlike the case of epoxidation with electrophilic agents (Section 5.05.4.2.2(f)) the stereochemical aspects of this and other epoxidations are reviewed at length in (B-73MI50500)). 

A number of reaction variables or parameters have been examined. Catalyst solutions should not be prepared and stored since the resting catalyst is not stable to long term storage. However, the catalyst solution must be aged prior to the addition of allylic alcohol or TBHP. Diethyl tartrate and diisopropyl tartrate are the ligands of choice for most allylic alcohols. TBHP and cumene hydroperoxide are the most commonly used terminal oxidant and are both extremely effective. Methylene chloride is the solvent of choice and Ti(i-OPr)4 is the titanium precatalyst of choice. Titanium (IV) t-butoxide is recommended for those reactions in which the product epoxide is particularly sensitive to ring opening from alkoxide nucleophiles. ... 

Strong evidence has been provided that the photoxygenation proceeds via a hydroperoxide intermediate which is transformed into an epoxide. The epoxide is then opened by the nucleophilic solvent. 

The epoxidation of electon-defident olefins using a nucleophilic oxidant such as an alkyl hydroperoxide is generally nonstereospecific epoxidation of both cis- and /nmv- ,/3-unsatii rated ketones gives the trans-epoxide preferentially. However, the epoxidation of cis-ofi-unsaturated ketones catalyzed by Yb-(40) gives civ-epoxides preferentially, with high enantioselectivity, because the oxidation occurs in the coordination sphere of the ytterbium ion (Scheme 26).132... 

Dialkylzinc reagents combine with BINOL to generate, in situ, a catalyst for homogeneous epoxidation of (/y)-o /3-enoncs to the corresponding f raws-epoxy ketones. TBHP and cumene hydroperoxide (CHP) are effective terminal oxidants for this process ees of up to 96% have been achieved. Mechanistic investigations point towards an electrophilic activation (Scheme 11) of the substrates by the chiral BINOL-zinc catalyst and a subsequent nucleophilic attack of the oxidant227... 

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