Cyclobutanone, homo-Favorskii rearrangement

The key step in the stereocontrolled total synthesis of the tricyclic (+)-kelsoene by M. Koreeda et al. was a base-catalyzed homo-Favorskii rearrangement of a y-keto tosylate to elaborate the 4-5 fused ring portion of the target molecule. The bicyclic 5-6 fused y-keto tosylate was treated with excess potassium fert-butoxide, which effected the desired rearrangement in less than 2 minutes at room temperature. The nucleophilic solvent was too bulky to effect the opening of the cyclobutanone intermediates, making their isolation possible. The mixture of isomeric cyclobutanones was converted to a separable 1 1 mixture of cyclobutanones with p-TsOH, and the ketone functionality was then removed via the corresponding tosylhydrazone. 

In the case of cyclic a-halo ketones, ring contraction occurs. A similar reaction occurs on )0-halo ketones via the elimination of a hydrogen halide to cyclobutanone followed by the scission of cyclobutanone, known as the homo-Favorskii rearrangement.This reaction has been proved to be a useful tool for synthesizing the highly strained esters. 

Transformations that use the initial steps of the homo-Favorskii rearrangement to prepare cyclobutanones are more common. When treated with base, ketone 6 generates cyclobutanone 8 via oxycyclopropane 7. ... 

If the halide is on the P -carbon instead of the a -carbon, then a rearrangement occurs through a cyclobutanone intermediate. This transformation is referred to as the homo-Favorskii rearrangement. Treatment of most P -haloketones with base would produce a, P -unsaturated ketones, so in order for the homo-Favorskii rearrangement to take place the... 

Wenkert and coworkers published the homo-Favorskii rearrangement shown below." Dienone 46 was subjected to Grignard conditions to give the methylated product 47. Acid-catalyzed isomerisation to a, 3-unsaturated ketone 48, followed by homo-Favorskii rearrangement under ethanolic KOH conditions yielded a mixture of chloroolefinic acid 49 and dienoic acid 50 via the cyclobutanone intermediate 51. 

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