Homo-Favorskii rearrangement

Both target compounds discussed in this review, kelsoene (1) and preussin (2), provide a fascinating playground for synthetic organic chemists. The construction of the cyclobutane in kelsoene limits the number of methods and invites the application of photochemical reactions as key steps. Indeed, three out of five completed syntheses are based on an intermolecular enone [2+2]-photocycloaddition and one—our own—is based on an intramolecular Cu-catalyzed [2+2]-photocycloaddition. A unique approach is based on a homo-Favorskii rearrangement as the key step. Contrary to that, the pyrrolidine core of preussin offers a plentitude of synthetic alternatives which is reflected by the large number of syntheses completed to date. The photochemical pathway to preussin has remained unique as it is the only route which does not retrosynthetically disconnect the five-membered heterocycle. The photochemical key step is employed for a stereo- and regioselective carbo-hydroxylation of a dihydropyrrole precursor. 

Full papers on lycoclavanin,135 lycoclavatol,136 the structure and partial synthesis of 16-oxoserratenes,137 the chemistry of serratriol, 21-episerratriol, and lyco-clavanol,138 and a homo-Favorskii rearrangement in the serratene series139 have been published. 

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. 

Zhang, L., Koreeda, M. Stereocontroiied Synthesis of Keisoene by the Homo-Favorskii Rearrangement. Org. Lett. 2002, 4, 3755-3758. 

The Favorskii-type rearrangements of chloroenamines such as (31) have received some investigation, and key results are presented in Scheme 45. Finally, the so-called homo-Favorskii rearrangement has been probed, and an example from the original work of Wenkert and coworkers is illustrated in Scheme 46. A partially successful homo-Favorskii rearrangement carried out on the diterpenoid (32 a derivative of virescenol A) is shown in Scheme 47, but the synthetic potential of this variant of the Favorskii rearrangement remains to be established. 

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. ... 

There are three significant variations on the Favorskii rearrangement, the homo-, quasi-, and photo-Favorskii rearrangements. The homo-Favorskii and quasi-Favorskii rearrangements oecur if the precursor does not possess the classic a-hydrogen and a -halide. The photo-Favorskii is a variation involving a light-induced radical mechanism. 

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. 

Neopentyl , Homo-Favorskii , abed-abde Rearrangements)... 

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