Ring contraction reactions Favorskii rearrangement

With cyclic a-halo ketones, e.g. 2-chloro cyclohexanone 6, the Favorskii rearrangement leads to a ring contraction by one carbon atom. This type of reaction has for example found application as a key step in the synthesis of cubane by Eaton and Cole for the construction of the cubic carbon skeleton ... 

The rearrangement with ring contraction probably is the most important synthetic application of the Favorskii reaction it is for example used in the synthesis of steroids. Yields can vary from good to moderate. As solvents diethyl ether or alcohols are often used. With acyclic a-halo ketones bearing voluminous substituents in a -position, yields can be low a tcrt-butyl substituent will prevent the rearrangement. 

This reaction is known as the Favorskii rearrangement,37 If the ketone is cyclic, a ring contraction occurs. 

The Favorskii reaction has been used to effect ring contraction in the synthesis of strained ring compounds. Entry 4 in Scheme 10.3 illustrates this application of the reaction. With 7,7 -dihalo ketones, the rearrangement is accompanied by dehydrohalo-genation to yield an a,/ -unsaturated ester, as illustrated by entry 3 in Scheme 10.3. 

The acid hydrolysis of cyclopropanone ethylene ketals to the corresponding esters appears to be a facile, high yield reaction (75—90%) which may be of synthetic importance. Thus, as shown in Scheme 29, a ring contraction similar to a Favorskii rearrangement may be achieved under mildly acidic conditions.107)... 

Favorskii rearrangement of cyclic 2-bromoketones leads to ring contraction and this has become one of the most fruitful uses of the rearrangement in synthesis. Bromination of cyclohexanone is a simple reaction (Chapter 21) and treatment with methoxide gives the methyl ester of cyclopentane carboxylic acid in good yield. 

This reaction is called the Favorskii rearrangement. Again, there are many variations for example, instead of an alkoxide anion, a hydroxide anion or even an amine may be used, in which case the salt of the carboxylic acid or the amide will be formed, respectively. This reaction may also be used so as to result in a ring contraction. Write down the mechanism for the reaction between an alkoxide anion and 2-chlorocyclohexanone. 

In the benzil-benzilic acid rearrangement, an a-diketone is treated with a base to give the sodium salt of an a-hydroxy carboxylic acid. In the Favorskii rearrangement, an a-halogenoketone is treated with an alkoxide anion to give the a-alkyl ester. This reaction may also be used to effect a ring contraction. 

In order to distinguish between a mechanism proceeding via a symmetrical cyclopropanone intermediate (Favorskii reaction) and a mechanism closely related to the benzilic acid rearrangement and called semibenzilic (or quasi-Favorskii) rearrangement, the ring contraction of 2-bromocyclobutanone was studied in deuterium oxide using sodium carbonate as base (50 C) or in boiling deuterium oxide only. 

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. 

Two groups have reported that reaction of 2-bromobicyclo[3,2,l]octan-3-one (557) under Favorskii rearrangement conditions (NaOMe-MeOH) gives mainly the substitution products (558) and (559) and very little of the ring-contraction products, the methyl 2-norbornanecarboxylates (largely exo-isomer). In... 

Contrary to what is observed in the Favorskii rearrangement, such a substitution product is seldom observed in the Ramberg-Backlund reaction, as cyclic a-halogenated sulfones generally give only the ring-contracted alkene under basic conditions. The sulfone which has a skeleton similar to the diene 37... 

---