Favorskii rearrangement, natural product synthesis

Cyclopropanone cleavage with elimination 72 can also lead to ring contraction as in the synthesis of the trans acid 74 from natural pulegone13 70. Bromination gives the unstable dibromide 71 that is immediately treated with ethoxide to initiate the Favorskii rearrangement. The product is a mixture of cis and trans isomers of the ester 73 but hydrolysis under vigorous conditions (reflux in aqueous ethanol) epimerises the ester centre and gives exclusively the trans acid 74. 

In the presence of base, a-haloketones rearrange to give acid derivatives depending upon the reaction conditions (equation 180). This very versatile reaction, the Favorskii rearrangement, has been the subject of several reviews966-968. The reaction was used in the synthesis of natural products, particularly steroids969-971, and the reader is referred to the reference sources for in-depth information. 

White and coworkers used a Favorskii rearranjgement in their synthesis of the natural product ( )-byssochlamic acid 17. 4-Ethylcyclohexanone 18 synthesized by Jones oxidation of the corresponding alcohol, was carboxylated to 19 and then dibrominated to 20. The Favorskii rearrangement was carried out with NaOMe to form the unsaturated diester... 

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