Alcohols, allylic epoxy ketones

Conversion of a-haloketones to olefins using hydrazine (via enedlitnides C-C-N NH). Also reduction of o,3-epoxy ketones to allyl alcohols. 

Wohf-Kishner reductions of a,jS-epoxy ketones give allylic alcohols, thus providing a means of reversing the arrangement in a,jS-unsaturated ketones or allylic alcohols. The reaction as first described by Wharton proceeds very readily (at room temperature in some instances) and the addition of strong base is unnecessary for example, the reduction of the epoxy ketone 143. 

Through a short sequence of functional group manipulations, compound 6 could be elaborated from allylic alcohol 7, the projected product of a Wharton fragmentation4 of epoxy ketone 8 (vide infra). In turn, compound 8 could be derived from enone 9. In the synthetic direction, a Michael addition5 of hydroperoxide anion to enone 9 would be expected to take place from the less hindered side of the molecule. Epoxy ketone 8 would fhen form upon collapse of the intermediate enolate with concomitant expulsion of hydroxide ion (see arrows, Scheme 2). 

Reduction of a,(3-epoxy ketones by hydrazine to allylic alcohols. 

The initially formed allylic chromate ester equilibrates with an isomeric chromate ester Both allylic chromate esters produce the epoxidation of the alkene. The resulting epoxy alcohols are oxidized to epoxy ketones A and B in a 5 3 ratio. Starting from an equatorial alcohol instead of an axial one, an uneventful oxidation to enone occurs without transposition. 

PCC reacts with tertiary allylic alcohols, forming an intermediate chromate ester that evolves giving a conjugated enone or enal. Sometimes, the isomeric chromate ester produces the epoxidation of the alkene, giving an epoxy alcohol that can be further oxidized to an epoxy ketone. 

A novel approach to the asymmetric synthesis of epoxides, allylic alcohols, a-amino ketones, and a-amino aldehydes from carbonyl compounds through a,/i-epoxy sulfoxides using the optically active p-tolylsulfmyl group to induce chirality./. Org. Chem. 1989, 54, 3130-3136. 

Epoxides will fragment if carbanions are formed adjacent to the epoxide ring. Decomposition of the hydrazone of an epoxy ketone in the presence of base may lead to an allylic alcohol (Scheme 2.24). Since the epoxy ketone may be prepared from an unsaturated ketone, this can form part of a sequence for the 1- 3 transposition of an oxygen function. 

A useful reduction reaction takes place with hydrazine in the presence of a strong base. In the Wolff-Kishner reduction a carbonyl group is reduced to a methylene. If the hydrazone is formed from an epoxy ketone, the decomposition takes place easily with the formation of an allylic alcohol. 

This system found another application—the oxidation of secondary alcohols into ketones in excellent yield. It is worthy of note that the oxidation procedure tolerates other functional groups including iodide, ester, terminal alkyne, aromatic ether, and 1,3-dioxolane. Certain secondary allylic alcohol such as 2-cyclododecen-l-ol (31) produced the corresponding epoxy ketone 32 in one pot, as exemplified in Sch. 17. 

Samarium iodide is a reagent capable of highly selective reduction of epoxy ketones and esters to the corresponding alcohols (Table 12). Diene monoepoxides are converted with high regio- and stereo-selectivity to the ( )-allylic alcohols, and the reaction can be carried out at -90 C under neutral conditions. As a result functional groups such as alkoxycarbonyl, carbonyl and cyano survive. 

This transformation has found extensive use in converting cyclopentenone and cyclohexenone ring systems to the rearranged allylic alcohols during the course of the total syntheses of natural products. In the preparation of ( )-quadrone (Scheme 12), the tricyclic enone was epoxidized and the resulting a,P-epoxy ketone treated with hydrazine to afford the allylic alcohol. The cyclopropane-directed epoxidation shown in Scheme 13 gives an allylic alcohol that is taken on to (-)- and (+)-carenones. In the total syn-... 

A novel reaction discovered by Wharton is the reduction of a,j8-epoxy ketones by hydrazine to allylic alcohols. When a suspension of the steroid (1) in excess 64% CHj CH,... 

The Wharton reaction is the transformation of a,(3-epoxy ketones 1 by hydrazine to allylic alcohols 2. It is also known as the Wharton transposition, Wharton rearrangement, and Wharton reduction. 

Reaction with a, -epoxy ketones. Swiss chemists have reported a case in which the Wharton reaction (1,, 439-440) led not only to the expected allylic alcohol but also to a product of cyclization. Stork and Williard have investigated this reaction in detail and have observed several more examples of the formation of cyclized allylic alcohols in the Wharton reaction as shown in the examples. On the other hand, several related systems were converted only into the products expected from a Wharton reaction. At the present time, the subtle factors that lead to cyclization are not well understood. 

The Wharton reaction converts an epoxy ketone to an allylic alcohol by reaction with hydrazine. Propose a mechanism. (Hint Review the Wolff-Kishner reaction in Section 19.9.)... 

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