Enol acetates epoxidation

The thermal or zinc bromide-catalysed isomerization of the enol acetate epoxides in the pinane series has been investigated. ... 

Solvolysis of the oxocyclohexylmethyl tosylate (617) gave the bicycloheptanones (618) and (619) (618) was rearranged by acid into the [3,2,0]-system (610). " Somewhat simils results have been reported for the 3,4-benzo-analogue of (617). The zinc bromide-induced isomerization of enol-acetate epoxides in the pinane series gives... 

Me3SiI, CH2CI2, 25°, 15 min, 85-95% yield.Under these cleavage conditions i,3-dithiolanes, alkyl and trimethylsilyl enol ethers, and enol acetates are stable. 1,3-Dioxolanes give complex mixtures. Alcohols, epoxides, trityl, r-butyl, and benzyl ethers and esters are reactive. Most other ethers and esters, amines, amides, ketones, olefins, acetylenes, and halides are expected to be stable. 

A commonly used alternative to the direct bromination of ketones is the halogenation of enol acetates. This can be carried out under basic conditions if necessary. Sodium acetate, pyridine or an epoxide is usually added to buffer the reaction mixture. The direction of enolization is again dependent upon considerations of thermodynamic and kinetic control therefore, the proportion of enol acetates formed can vary markedly with the reaction conditions. Furthermore, halogenation via enol acetates does not necessarily give the same products as direct halogenation of ketones 3. 23... 

Hydroxyl groups are stable to peracids, but oxidation of an allylic alcohol during an attempted epoxidation reaction has been reported." The di-hydroxyacetone side chain is usually protected during the peracid reaction, either by acetylation or by formation of a bismethylenedioxy derivative. To obtain high yields of epoxides it is essential to avoid high reaction temperatures and a strongly acidic medium. The products of epoxidation of enol acetates are especially sensitive to heat or acid and can easily rearrange to keto acetates. 

Three possible mechanisms for the Serini reaction were originally suggested. These proceed via (a) a A -enol acetate, (b) a A -epoxide, or (c) a cyclic orthoester ... 

Epoxidation of the A -enol acetate was originally carried out with per-benzoic acid. Monoperphthalic acid has also been used, but is apparently more susceptible to steric and conformational factors. The commercially available peracetic acid is generally most convenient. Based on the expected backside attack, the derived epoxides have the 17a configuration, and hydrolysis always produces the 17a-hydroxy group. 

C-20 enol acetates react with peracids in the same manner as their C-17(20) counterparts, giving a 20,21-epoxide capable of cleavage to the 21-hydroxy-20-ketone ... 

When this reaction sequence is applied to enol esters or enol ethers, the result is a-oxygenation of the starting carbonyl compound. Enol acetates form epoxides that rearrange to a-acetoxyketones. 

Enol acetates form epoxides which can rearrange to a-acetoxy ketones ... 

EpoxyacetateB have also keen prepared from steroid end aoetatc by Huechmann and Wendler,7 Soloway and co-workers,1801 and Leeds and eo-workers.888 Moffett and Stomp 187 have found, with certain unsatorated steroid enol acetates, that where a choice reaction sites exists perbenzoic add attacks a simple olefinie double bond preferentially. At higher temperatures and with excess l peroxy add, however, there ooouzs epoxidation of the enol acetal... 

In a situation where severe steric hindrance (e.g., 16,16-dimethyl-20-keto-pregnanes) prevents enol acetate formation, an alternate scheme has been devised. Condensation of ethyl oxalate at C-21 produces, after hydrolysis, the 21-glyoxylic acid this on treatment with acetic anhydride and a strong acid catalyst such as perchloric acid gives both A17(20)-enol lactone acetates. Epoxidation with peracid, and mild alkaline hydrolysis proceeds to give the 17a-hydroxy-20-ketone in a high overall yield.257... 

Steroidal enol acetates were similarly epoxidized. This method has undoubted advantages over the tradional epoxidation by peracids. Metal-catalyzed epoxidation of 1-acetoxycyclohexene is a key step in a novel synthesis of catechol from cyclohexanone via the sequence465... 

While enol acetates from saturated ketones were useful a-oxygenation substrates, the corresponding dienol acetates are not. The relatively electron-deficient alkene bearing the acetoxy group is less attractive h> elecm hilic oxygenating agents than the unsubstituted double bond. Thus, for example, peracid treatment leads to epoxidation the unfiinctionalized alkene.However, it would seem likely that re-... 

Epoxides derived from enol acetates undergo rearrangement under quite mild acidic conditions, including chromatography... 

C-7 Ketones are readily available from the aromatic acids such as dehydro-abietic acid. Epoxidation of the enol-acetate derived from the 7-ketones,... 

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