Wharton reaction mechanisms

The mechanism of the Wharton reaction is analogous to that of the Wolff-Kishner reduction. Addition of hydrazine to a, 3-epoxy ketone 1 gives rise to hydroxyl-hydrazine 6, which dehydrates to afford the intermediate, hydrazone 7. Tautomerization of hydrazone 7 then leads to diazene 8, a common intermediate as the Wolff-Kishner reduction. But different... 

No sooner than Wharton s landmark publications did Dodson of G. D. Searle discover a side reaction of the Wharton reaction.7 Treatment of 16a,17-epoxypregnenolone (9) with hydrazine hydrate resulted in not only the expected allylic alcohol 10 (ca. 25% yield), but also a small amount of pyrazole 11 (ca. 10% yield) as well. It was speculated that the mechanism involved an intramolecular Sn2 displacement of the epoxide by the diazene (the anchimeric process) followed by dehydration.8... 

An interesting reaction has been reported by Stork. Treatment of an unsaturated keto epoxide such as 264 with hydrazine in methanol gives the bicyclic compound 266 in 85% yield instead of the expected allylic alcohol from the Wharton reaction. A concerted mechanism and a free radical mechanism have been considered by Stork and, indeed, a free radical mechanism seems in accord with the other results described. This mechanism... 

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.)... 

Similar fragmentations to produce S-cyclodecen-l-ones and 1,6-cyclodecadienes have employed l-tosyloxy-4a-decalols and 5-mesyloxy-l-decalyl boranes as educts. The ringfusing carbon-carbon bond was smoothly cleaved and new n-bonds were thereby formed in the macrocycle (P.S. Wharton, 1965 J.A. Marshall, 1966). The mechanism of these reactions is probably E2, and the positions of the leaving groups determine the stereochemistry of the olefinic product. 

The mechanism of the Wharton transposition is very simiiar to that of the Woiff-Kishner reaction. The epoxyhydrazone is first deprotonated, which triggers the faciie and irreversible epoxide ring-opening. The C-N bond of the resuiting vinyi diazene is broken upon another deprotonation, releasing N2 and a vinyl anion, which in turn affords the desired aiiyiic aicohoi. Aiternativeiy, the formation of a vinyi radical has been proposed. ... 

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