Ketones, 2-halo 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 reaction of oc-halo ketones (chloro, bromo, or iodo) with alkoxide ions rearranged esters is called the Favorskii rearrangement. 

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. 

The Favorskii Rearrangement. When treated with base, a-halo ketones undergo a skeletal change that is similar to the pinacol rearrangement. The most commonly used bases are alkoxide ions, which lead to esters as the reaction products. This reaction is known as the Favorskii rearrangement.84... 

When one attempts E2 reactions with a-halo ketones using strong bases such as alkoxides, an interesting rearrangement pathway may occur called the Favorskii rearrangement. In this reaction, the a-halo ketone is converted to an ester. For example, 2-chlorocyclohexanone is converted to the methyl ester of cyclopentanecarboxylic acid by treatment with sodium methoxide in ether ... 

The Favorskii rearrangement results from the action of base on an a-halo ketone. When applied to cyclic ketones, ring contraction results, as shown in the classic case of cyclohexanone formulated below. 

A typical Favorskii rearrangement involves reaction of an a-halo ketone with a base to give an ester or carboxylic acid, as in the following example ... 

The mechanism discussed is in accord with all the facts when the halo ketone contains an a hydrogen on the other side of the carbonyl group. However, ketones that do not have a hydrogen there also rearrange to give the same type of product. This is usually called the quasi-Favorskii rearrangement. An example is found in the preparation of Demerol ... 

Favorskii rearrangement Skeletal rearrangement of a-halo ketones via a cyclopropanone intermediate to give carboxylic acids or carboxylic acid derivatives. 164... 

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. 

The structural equivalence of the starting materials with respect to their common rearrangement product has already been mentioned, and two further examples are illustrated in Scheme 11. ° In practice this often means that the ketone can be halogenated, and the mixture of halo ketones used directly in the Favorskii rearrangement. 

The whole process comprising the conversion of an a-halo ketone into a cyclopropanone, the adduct formation, and subsequent ring opening into carboxylic acid derivatives (carboxylic esters, carboxylic acids or carboxylic amides by using alkoxides in alcohols, hydroxides in water or amines in various solvents, respectively) is known as the Favorskii rearrangement. 

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