Wharton rearrangement

Alkene formation also took place upon attempted deoxygenation of ITC derivatives of 2,3-epoxy alcohols. This radical-based alternative to the Wharton rearrangement is shown in equation (17), and is analogous to the rearrangement of cyclopropylcarbinyl radicals. 

Barton, D. H. R., Motherwell, R. S. H., Motherwell, W. B. Radical-induced ring opening of epoxides. A convenient alternative to the Wharton rearrangement. J. Chem. Soc., Perkin Tmns. 11981, 2363-2367. 

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. 

This reaction is related to the Bamford-Stevens Reaction, Grob Fragmentation and Wharton Rearrangement. 

The radical-induced epoxide ring-opening of a,/3-epoxy-0-thiocarbonyl-imidazolides (23) [equation (3)] has been reported to be a convenient alternative to the Wharton rearrangement (action of hydrazine on epoxides of a,/3-unsaturated ketones) for production of allylic alcohols. /3,y-Disubstituted allylic alcohols with Z-conhguration are the major products formed on addition of alkyl-lithiums to the vinyl epoxide (24) [equation (4)]. ... 

Wharton, P. S. Bohlen, D. H. Hydrazine Reduction of Epoxy Ketones to Allylic Alcohols /. Or. Chem. 1961, 26, 3615-3616. For a mechanistic study see Stork, G. Williard, P. G. Five- and Six-Membered-Ring Formation from Olefinic a,j8-Epoxy Ketones and Hydrazine /. Am. Chem. Soe. 1977, 99, 7067-7068. For a recent appUcation of the Wharton rearrangement see Liu, J. Hsung, R. P. Peters, S. D. Total Syntheses of (+)-Cylindricines C-E and (-)-Lepadiformine through a Common Intermediate Derived from an z -Prins Cyclization and Wharton s Rearrangement Oi. Lett. 2004, 6, 3989-3992. 

Next, a three-step sequence was employed to convert diastereomeric spirocycles 415 to epoxy ketone 416. This intermediate was subjected to a Wharton rearrangement using 5.0 equiv hydrazine and 0.5 equiv HO Ac to yield the desired transposed allyl alcohol 417-trans in 66% yield as an inseparable diastereomeric mixture. While we observed this tra/w-allyl alcohol in most trials, we found the c/r-allyl alcohol 417-c/r in 42% yield when using 10 equiv HOAc. 

Scyphostatin (Scheme 57.17) is the most potent reversible inhibitor of neutral sphingomyelinase. Its biological activity is believed to be associated with the polar epoxycy-clohenenone subunit. A precursor of this subunit is the acetyl derivative 68. Hoye et al. have described an interesting stereoselective route toward 68 starting from the L-tyrosine derivative 64. By means of two oxidation steps, compound 64 was selectively transformed into the 5yn-diepox-ide 65, which was converted via a Wharton rearrangement into a 1 1 mixture of diastereomeric epoxycyclohexenols 66 and 67. 

Wharton reaction (1, 439 8, 245). This reaction can also be conducted under free-radical conditions of reduction of thiocarbonylimidazolide derivatives of a,/l-epoxy alcohols with tri-n-butyltin hydride.17 In some cases, inverse addition is necessary to prevent further rearrangement of the allylic alcohol initially formed. Yields are around 50-60%. The modification is not useful in the carbohydrate field, where very complex product mixtures are formed. 

Wharton reaction2 (1, 439-440). This rearrangement of a,3-enones to allylic alcohols via an epoxy hydrazone has seen only occasional use outside of the sterol field because yields can be low. Some expedients have been shown by Dupuy and... 

The same authors [81] performed the transformation of the keto acetate (31) into biologically active warburganal (16) by two convergent pathways, (Scheme 19). According to one of them, compound (31) was epoxidised, and the epoxy ketone (116) was subjected to a Wharton-Bollen rearrangement. The resulting diol (117) was acetylated to give the... 

Three years ago Corey and Broger °" attempted the synthesis of hedycaryol (210) but found that a Cope rearrangement of one of the intermediates could not be prevented under the experimental conditions and thus they achieved a synthesis of elemol. Wharton et using a different approach to generate the... 

Wagnei-Meerwein rearrangement, 450 Wharton reaction, 245 Wieland-Miescher ketone, 423... 

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