Ketones, unsaturated with alkaline hydrogen peroxide

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-... 

Epoxidation of a, -Unsaturated Ketones with Alkaline Hydrogen Peroxide ... 

Reports have appeared claiming that triperoxo vanadates behave as nucleophilic oxidants. In particular, triperoxo vanadium complexes, A[V(02)3]3H20 (A=Na or K), are proposed as efficient oxidants of a,-unsaturated ketones to the corresponding epoxide, benzonitrile to benzamide and benzil to benzoic acid, reactions which are usually carried out with alkaline hydrogen peroxide. Subsequent studies concerning the oxidation of cyclobutanone to 4-hydroxybutanoic acid, carried out with the above-cited triperoxo vanadium compound, in alcohol/water mixtures, clearly indicated that such a complex does not act as nucleophilic oxidant, but only as a source of HOO anion. 

Epoxldation of a, -uusaturated ketones. Some years ago, /-butyl hydroperoxide in the presence of a basic catalyst (Triton B) was reported to epoxidize unhindered a,/3-unsaturated ketones in yields comparable to those obtained with alkaline hydrogen peroxide (1, 88). This reaction results in Michael adducts in the case of acrylonitrile or methyl acrylate. 

The double bond of an unsaturated ketone is deactivated towards electrophilic attack by the electron-withdrawing carbonyl group but is susceptible to nucleophilic addition. Base-catalysed epoxidation with alkaline hydrogen peroxide provides a useful method for the synthesis of a,P-epoxy ketones. 

The most dependable reagent for the epoxidation of unsaturated ketones is hydrogen peroxide, especially in alkaline media [142, 143, 149, 151]. Because the Baeyer-Villiger reaction is acid-catalyzed, it does not take place during epoxidations with alkaline hydrogen peroxide or its neutral derivatives, such as fe/ t-butyl hydroperoxide [220]. Most examples of epoxidation involve unsaturated ketones with conjugated double bonds. 

Oxidation of a,P-unsaturated ketones with alkaline hydrogen peroxide produces the corresponding keto epoxides in good yields. This nucleophilic epoxidation proceeds via an initial Michael-type addition of the hydroperoxide anion to the enone system, which is then followed by elimination of HO. It should be noted that the inductive electron-withdrawing effect of the neighboring oxygen in HOO makes it a weaker base than HO" but a better nucleophile than hydroxide. 

In contrast to the stereospecific epoxidation of acyclic alkenes with peroxy acids, oxidation of acyclic a,(3-unsaturated ketones with alkaline hydrogen peroxide is stereoselective in that only one stereoisomer is formed from cis- and trans-enones ... 

C.A. Bunton, G.J. Minkoff (1949). Oxidation of a,/S-unsaturated ketones with alkaline hydrogen peroxide. J. Chem. Soc., 665-670. 

Alkaline Hydrogen Peroxide. ajS-Unsaturated ketones (123) were epoxidized with alkaline hydrogen peroxide to form 4/5,5/ -epoxyandrostane-6,17-diones (124). The presence of a 3j -hydroxy-group was found to be advantageous during epoxidation. Initial attempts to epoxidize zerumbone (125)... 

Although used predominantly with a,j5-unsaturated ketones thus far, the alkaline hydrogen peroxide reagent has also been found to react with., j3-unsaturated nitriles110 131Si 1117 and. more recently with 3-uiwattiratod aldehydes " 1311 and esters.1210 131 ... 

As previously mentioned, 1-alkynyltrialkylborates (18) have become increasingly important in the formation of carbon-carbon bonds via attack of electrophiles. However, such complexes cannot react with simple Qc,P-unsaturated carbonyl compounds such as methyl vinyl ketone, because of their weak electrophilicity. Recently it was ascertained that ,P-unsaturated carbonyl compounds react with 18 via a Michael-type reaction in the presence of titanium tetrachloride, and the usual alkaline hydrogen peroxide oxidation leads to the synthesis of 5-dicarbonyl compounds... 

Alkaline hydrogen peroxide reacts with a jS-unsaturated ketones by a different reaction sequence, exemplified by the behaviour of "A-nor-testosterone 27) [7 ]. The reagent first converts the steroid into the corresponding epoxy-ketone 28) by the mechanism discussed on p. 201, and only then brings about a Baeyer-Villiger oxidation of the ketone function to give the epoxy-lactone (29) as the major product. 

The epoxidation of electron deficient alkenes such as methyl methacrylate has also been carried out using reaction conditions similar to those shown in Eq. (15), and with a,p-unsaturated ketones alkaline hydrogen peroxide has been generated from UHP and affords good yields of epoxides. Pulegone gave a 50% yield of the epoxide and the result obtained with isophorone is shown in Eq. (16). 

Synthetic polypeptides were found, by Julia, to epoxidize a, i-unsaturated ketones with high enantioselectivity [12], The Julih process can be easily performed at O C, and using a triphasic system comprising of toluene, water and polyalanine in the presence of alkaline hydrogen peroxide, chalcone oxide was produced in 97% ee (Scheme 1.7). The Julia process has become the method of choice for the epoxidation of fran.y-l,3-diarylenones. However, this methodology is extremely substrate-specific, and enones with enolisable a-protons are usually poor substrates. 

However, as Weitz and Scheffer found,43 <%,/ -unsaturated ketones give epoxy ketones in reaction with hydrogen peroxide in alkaline solution. 

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