Anions Favorskii rearrangement

In order to activate the 21 position to halogenation, it is hrst converted to an oxalate. Condensation of the triketone with ethyl oxalate in the presence of alkoxide proceeds preferentially at the 21 position to give (12-2) due to the well-known enhanced reactivity of methyl ketones. Reaction of the crude sodium enolate with bromine leads to the dibromide (12-3), the oxalate moiety being cleaved under the reaction conditions. The Favorskii rearrangement is then used to, in effect, oxidize the 17 position so as to provide a site for the future hydroxyl group. Thus, treatment of (12-3) with an excess of sodium methoxide hrst provides an anion at the 17 position (12-4). This then cyclizes to the transient cyclopropanone (12-5)... 

However, this is a special case reaction known as the Favorskii rearrangement. As illustrated below using arrow pushing, sodium hydroxide extracts a proton adjacent to the ketone, and the resulting anion displaces the bromide ion, generating a new three-membered ring. 

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. 

Sterically crowded a-haloketones and a-haloketimines cyclize to cyclopropanones and ketiinines, respectively, upon treatment with bases. The reaction of a series of a-haloketones with dialkyl sodiomalonate has been found to give the adducts of the malonate anion to incipient cyclopropanones, i.e. (l-hydroxycyclopropyl)malonic esters, instead of the products of the Favorskii rearrangement . Cyclopropanone aminals and l-alkoxycyclopropylamines have been obtained in the reactions of cyclic a-chloroketones (equation 16) with secondary amines and of a-chloroketimines with... 

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. 

A conceivable mechanism for this reaction considers that malonate anion initially reacts as a base to give an equilibrium mixture of zwitterion 2 and cyclopropanone 3 intermediates, which have been suggested to be involved in the Favorskii rearrangement. ... 

In the conversion of 17 to 18 -17 NaH may form the enolate at the 0=C—C—SePh carbon. Although it may be less favored, it formation of a three-membered ring possible (see Favorskii rearrangement) Can the enolate anion displace the Cl across the ring ... 

Scheme 7.44. A representation of a pathway to cyclopentanecarboxylic acid anion from 2-chlorocyclohexanone (the Faworsky [Favorskii] rearrangement). The path is presumed to take place via y- (or 1,3) elimination of hydrogen chloride (FICl) through a substituted cyclo-propanone intermediate.

The base-catalysed rearrangements of cz-halo ketones are classical examples of the reactions of ambident enolate anions in solution. The extent of each of the two reactions shown in Equations [11] and [12] is principally a function of the type of solvent used. A protic solvent solvates more strongly at the oxygen centre of the ambident anion and thus reaction proceeds through the carbanion centre to yield the Favorskii species as the major product (Eqn [11]). In marked contrast, the Favorskii rearrangement does not occur in the gas phase. Here,... 

Favorskii rearrangement occurs through the formation of a cyclopropanone intermediate, such as 3, which is later cleaved giving the carboxylic acid (or derivative) after protonation. When there is an option, the cleavage occurs to give the most stable anion (cf. Scheme 18.4). This mechanism is illustrated for the reaction of a-chlorocyclohexa-none 1 with methoxide anion in Scheme 18.1. Altonative mechanisms have also been proposed. " ... 

Barbee TR, Guy H, Heeg MJ, Albizati KF. Functional group hybrids. Reactivity of a -nucleofuge a,(3-unsaturated ketones. 2. Reactions with malonate anion. Concerning the mechanism of the Favorskii rearrangement. J. Org. Chem. 1991 56 6773-6781. 

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