By the Favorskii rearrangement

Cycloundecanecarboxylic acid has been prepared by the bromination of cyclododecanone followed by the Favorskii rearrangement of 2-bromocyclo-dodecanone... 

The methyl ester has also been obtained by esterification of cyclopentanecarboxylic acid.8 The acid, in turn, has been prepared by the Favorskii rearrangement,6 7 9-11 by the reaction of cyclopentyl Grignard reagent with carbon dioxide,12 by the carbonylation of cyclopentyl alcohol with nickel carbonyl13 or with formic acid in the presence of sulfuric acid,14 and by the hydrogenation of cyclopentene-1-carboxylic acid prepared from ethyl cyclopentanone-2-carboxylate 15 or from cyclopentanone cyanohydrin.16... 

Another useful route to cyciopentanes is the ring contraction of 2-bromo-cydohexanones by a Favorskii rearrangement to give csrdopcntanecarboxylic acids. If a 0 dibromoketones are used, ring opening of the intermediate cydopropanone leads selectively to, y-unsaturated carboxylic acids (S.A, Achmad, 1963, 1965 J. Wolinsky, 1965). 

The currently accepted mechanism for the Favorskii rearrangement of dihalo ketones involves a cyclopropanone intermediate formed by loss of HX. This is followed by attack of alkoxide synchronous with cyclopropanone fragmentation and departure of halide ion to form the unsaturated ester... 

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 ... 

We see from these examples that many of the carbon nucleophiles we encountered in Chapter 10 are also nucleophiles toward aldehydes and ketones (cf. Reactions 10-104-10-108 and 10-110). As we saw in Chapter 10, the initial products in many of these cases can be converted by relatively simple procedures (hydrolysis, reduction, decarboxylation, etc.) to various other products. In the reaction with terminal acetylenes, sodium acetylides are the most common reagents (when they are used, the reaction is often called the Nef reaction), but lithium, magnesium, and other metallic acetylides have also been used. A particularly convenient reagent is lithium acetylide-ethylenediamine complex, a stable, free-flowing powder that is commercially available. Alternatively, the substrate may be treated with the alkyne itself in the presence of a base, so that the acetylide is generated in situ. This procedure is called the Favorskii reaction, not to be confused with the Favorskii rearrangement (18-7). ... 

Quantum mechanical/molecular mechanical study on the Favorskii rearrangement in aqueous media has been carried out.39 The results obtained by QM/MM methods show that, of the two accepted mechanisms for Favorskii rearrangement, the semibenzilic acid mechanism (a) is favored over the cyclopropanone mechanism (b) for the a-chlorocyclobutanone system (Scheme 6.2). However, the study of the ring-size effects reveals that the cyclopropanone mechanism is the energetically preferred reactive channel for the a-chlorocyclohexanone ring, probably due to the straining effects on bicycle cyclopropanone, an intermediate that does not appear on the semibenzilic acid pathway. These results provide new information on the key factors responsible for the behavior of reactant systems embedded in aqueous media. 

As usual, the key to this problem is numbering correctly. The main question is whether the ester C in the product is C3 or C4. Because a ring contraction from 6- to 5-membered is likely to proceed by a Favorskii rearrangement, where the last step is cleavage of a cyclopropanone, it makes sense to label the... 

Semiempirical calculations on the Favorskii rearrangement of a-chlorocyclobutan-one to cyclopropenecarboxylic acid suggest that it proceeds via a stepwise semibenzilic acid pathway, both in solution and in vacuo, rather than by a cyclopropanone... 

The Favorskii [213] and Ramberg-Backlund [214] rearrangements are mechanistically akin to the above. The first step is deprotonation (although in highly strained systems the Favorskii rearrangement proceeds by donor addition to the carbonyl group) which is followed by internal displacement of the a-halogen. 

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 ... 

Once again the only reasonable way to disconnect such an ester is to reverse the rearrangement in your mind, adding the halide at a reasonable position. So 67 might be made by reversing the Favorskii rearrangement 75 and only when you see the simple starting material 66 can you... 

The synthetic utility of the Favorskii rearrangement is somewhat reduced by side-reactions including substitution of the halogen atom, elimination to form unsaturated ketones and epoxide formation. However, if the starting ketone is polyhalogenated, then... 

This means that it can be used to build up heavily branched esters and carboxylic acids—the sort that are hard to make by alkylation because of the problems of hindered enolates and unreactive secondary alkyl halides. Heavily substituted acids, where CO2H is attached to a tertiary carbon atom, would be hard to make by any other method. And the Favorskii rearrangement is a key step in this synthesis of the powerful painkiller Pethidine. 

So how can the cycloaddition be promoted at the expense of the Favorskii rearrangement Nothing can be done about the equilibrium between the oxyallyl anion and the cyclopropanone— that s a fact of life. The answer is to reduce the nucleophilicity of the alcohol by using trifluoro-ethanol instead of ethanol. Under these conditions the major product is the cycloadduct, which can be isolated in 73% yield. 

Other symmetrical intermediates originaliy identified by radioactive labelling include the cyciopropanone in the Favorskii rearrangement in Chapter 37, p. 990, and a spirocyclic intermediate in electrophilic substitution on an Indole in Chaptar 43, p. 1170. 

Exposure of uvidin A (3.14) or the esters 3.16-3.20 to methanolic KOH led to the new lactone 3.38, arising by a Favorskii rearrangement of the a,P-epoxyketone function (11). The same rearrangement was observed for 11-O-ethoxyethyluvidin A however, in this case the lactone ring involved the tertiary OH group of compound 3.39. Sesquiterpenes 3.38 and 3.39 have a new... 

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