Favorskii rearrangement

The reaction is named for the Russian chemist Alexei Yevgrafovich Favorskii.^[2][3][4]

The reaction became popular for the synthesis of strained cyclic compounds in the 1970s.^[5] For example, cubane synthesis proceeds by Favorskii rearrangements:^[6]

The Favorskii rearrangement begins when an enolate forms on the side of the ketone away from the chlorine atom. This enolate cyclizes to a cyclopropanone intermediate. In aprotic solvents, the process is concerted, and thus stereospecific, inverting configuration at the halide-substituted carbon. In protic solvents, the process is stepwise, with chloride anion leaving first. The resulting achiral, cationic oxyallyl 1,3-dipole then undergoes a disrotatory, 2-electron electrocyclization to the cyclopropanone.^{[7]: 733, 741–743} In either case, the base then attacks the cyclopropanone. Finally, the ring opens to yield the more stable carbanion, which is quickly protonated:^[8]

When enolate formation is impossible, harsh reaction conditions can still sometimes induce a similar reaction, called the pseudo- or quasi-Favorskii rearrangement. The alternate reaction pathway probably resembles the benzilic acid rearrangement: base initially adds to the ketone, and the resulting acetal anion collapses in concert with carbon migration and halide expulsion.^[9]

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^[10][11]

α,α'‑Dihaloketones eliminate HX under the reaction conditions to give α,β-unsaturated carbonyl compounds,^{[9]: 262 [12]} but α,α,α'‑trihaloketones generally do not undergo a second elimination to the ynone.^[9]: 262

Trihalomethyl ketone substrates undergo the haloform reaction instead.

Favorskii rearrangements also occur through photochemical excitation. The photo-Favorskii reaction has been used to unlock certain phosphates (for instance those of ATP) protected as para‑hydroxy­phenyl­acetate esters.^[13] The deprotection is believed to proceed through a triplet diradical (3) and a dione spiro intermediate (4), although the latter has thus far eluded detection:^[14]

• Benzilic acid rearrangement — similar carboxylate extrusion
• Trimethylenemethane cycloaddition, which can proceed via a similar mechanism
• Homo-Favorskii rearrangement, the rearrangement of β-halo ketones and cyclobutanones
• Wolff rearrangement - can react similarly
• Dowd-Beckwith ring-expansion reaction — radical analogue (when applied to single-carbon expansions)