Favorskii rearrangement Subject

The subjects of this section are two reactions that do not actually involve carbo-cation intermediates. They do, however, result in carbon to carbon rearrangements that are structurally similar to the pinacol rearrangement. In both reactions cyclic intermediates are formed, at least under some circumstances. In the Favorskii rearrangement, an a-halo ketone rearranges to a carboxylic acid or ester. In the Ramberg-Backlund reaction, an a-halo sulfone gives an alkene. 

Through the years, the mechanism147 of the Favorskii rearrangement has been the subject of much investigation at least five different mechanisms have been proposed. However, the finding148 that 54 and 55 both give 56 (this behavior is typical) shows that any mechanism... 

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. 

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. 

The rearrangement of a-halo ketones under the influence of base was first described by Favorskii in 1892, and the general scope of the reaction and the mechanistic implications have been the subject of a number of reviews. In its most generally useful form, a-halo ketones undergo skeletal rearrangement when treated with a nucleophilic base (hydroxide, alkoxide or amine) to produce salts, esters and amides respectively (Scheme 1). With polyhalogenated ketones unsaturated acid derivatives are prcxluced, as shown in Scheme 2. 

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