Epoxy ketones, hydrogenation

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-... 

Treatment of an or.jS-unsaturated ketone with basic aqueous hydrogen peroxide yields an epoxy ketone. The reaction is specific to unsatnrated ketones isolated alkene double bonds do not react. Propose a mechanism. 

Pyrazoles were synthesized in the authors laboratory by Le Blanc et al. from the epoxy-ketone as already stated in Sect. 3.1.1a, Scheme 35 [80]. The synthetic strategy employed by Le Blanc et al. [80] was based upon that the strategy published by Bhat et al. [81] who also described the synthesis of pyrazoles but did not report cytotoxic evaluation on the synthesized compounds. Scheme 48 shows the synthesis of the most active compound (178). Dissolution of the epoxide (179) with a xylenes followed by treatment with p-toluenesulfonic acid and hydrazine hydrate produced the pure nitro-pyrazole 180 in good yield (60%). Catalytic hydrogenation with palladium on activated carbon allowed the amino-pyrazole (178) to be obtained in a pure form. This synthesis allowed relatively large numbers of compounds to be produced as the crude product was sufficiently pure. Yield, reaction time, and purification compared to reported approaches were improved [50, 61, and 81]. Cytotoxicity of these pyrazole analogs was disappointing. The planarity of these compounds may account for this, as CA-4, 7 is a twisted molecule. 

As a, (3-unsaturated ketones are electron-poor alkenes, they do not generally give epoxides when treated with peracids. They can be epoxidized with hydrogen peroxide which involves nucleophilic attack by HOO- to give the epoxy ketone (Figure 4.1). 

Hydrogenation of the a -epoxy ketone shown in Eq. 365) over platinum in ethyl aoet te was found by Reese1441 to leave the epoxide ring intact. Tetrasubstituted ethylene oxides are notoriously unremaivc toward most reagents, and catalytic reduction proves to be unexceptional in this respect. 

Waaserman and Aubrey1 extended this type of investigation lo include the cw- and trans-isomers of dypnone oxide. Chtarohydrins obtained on treatment of these ,j9-epoxy ketones with hydrogen chloride in aoetic acid could be recydized into dypnone oxides of... 

A modest assortment of storoidal e -epoxy ketones (EqB. 737-740) have been subjected to the action of hydrogen halides, among them... 

Epoxidation of enones on treatment with basic hydrogen peroxide or /-butyl hydroperoxide, or with bleach, might be viewed as another form of trapping the initially produced anion.99 In this case the enol-ate, e.g. (425 Scheme 57), attacks the oxygen of the hydroperoxide to eject hydroxide and yield the epoxy ketone (426)." Finally, the initial anion can also be trapped by a sigmatropic rearrangement, as in... 

These reactions become more realistic if derivatives of a,/3-epoxy ketones are used. These can be easily prepared by oxidation of the corresponding a,/3-unsa-turated ketones with peracids or hydrogen peroxide (Scheme VIII/13). The driving force in studying this kind of reactions is the importance of the economic synthesis of the natural 15-membered ketones, muscone and cyclopentadeca-none, from cyclododecanone, an easy available and inexpensive starting material (Scheme VIII/14) [35] [36]. 

Epoxy ketone 10 was prepared from the enone 9 by the action of alkaline hydrogen peroxide and used for the synthesis of arglanine71. 

Epoxy ketones are prepared by the action of hydrogen peroxide on unsaturated ketones in alkaline medium. In this manner, dlbenzoyl-ethylene oxide (86%) is prepared from both cis- and traws-dlbenzoyl-ethylene. ... 

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 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. 

Under irradiation conditions, imidazolines are excellent hydrogen donors. For example l,3-dimethyl-2-phenylben-zyimidazoline 639 reduces a,(3-epoxy ketones in the presence of proton donors (Scheme 152) <2001S1248>). 

The Eschenmoser fragmentation uses a tosyl hydrazone of an cr,/S-epoxy-ketone (p. 1008). epoxide can be made with alkaline hydrogen peroxide and the tosylhydrazone needs tosylhydrazine to form what is simply an imine. Then the fiin can begin. The stereochem y doesn t matter for once. 

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