Favorskii rearrangement

The Favorskii rearrangement, named for the Russian chemist Alexei Yevgrafovich Favorskii, is most principally a rearrangement of cyclopropanones and α-halo ketones which leads to carboxylic acid derivatives. In the case of cyclic α-halo ketones, the Favorskii rearrangement constitutes a ring contraction. This rearrangement takes place in the presence of a base, sometimes hydroxide, to yield a carboxylic acid but most of the time either an alkoxide base or an amine to yield an ester or an amide, respectively. α,α’-Dihaloketones eliminate HX under the reaction conditions to give α,β-unsaturated carbonyl compounds.^{[1][2][3][4][5][6][7][8]}

Reaction mechanism

The reaction mechanism is thought to involve the formation of an enolate on the side of the ketone away from the chlorine atom. This enolate cyclizes to a cyclopropanone intermediate which is then attacked by the hydroxide nucleophile.

Usage of alkoxide anions such as sodium methoxide, instead of sodium hydroxide, yields the ring-contracted ester product.

An animation of the reaction mechanism

Wallach degradation

In the related Wallach degradation (Otto Wallach, 1918) not one but two halogen atoms flank the ketone resulting in a new contracted ketone after oxidation and decarboxylation^[9][10]

Photo-Favorskii reaction

The reaction type also exists as a photochemical reaction. The photo-Favorskii reaction has been used in the photochemical unlocking of certain phosphates (for instance those of ATP) protected by so-called p-hydroxyphenacyl groups.^[11] The deprotection proceeds through a triplet diradical (3) and a dione spiro intermediate (4) although the latter has thus far eluded detection.^[12]

See also

• A classic cubane synthesis contains two Favorskii rearrangements.
• Trimethylenemethane cycloaddition which can proceed via a similar mechanism

References