Favorskii rearrangement

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Favorskii rearrangement
Named after Alexei Yevgrafovich Favorskii
Reaction type Rearrangement reaction
Identifiers
Organic Chemistry Portal favorsky-reaction
RSC ontology ID RXNO:0000385

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]

The Favorskii rearrangement

Reaction mechanism[edit]

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.

Favorskii rearrangement mechanism

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

An animation of the reaction mechanism of the Favorskii rearrangement
An animation of the reaction mechanism

Wallach degradation[edit]

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[edit]

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]

Photo Favorskii Givens 2008

See also[edit]

References[edit]

  1. ^ Favorskii, A. E. J. Russ. Phys. Chem. Soc. 1894, 26, 590.
  2. ^ Favorskii, A. E. J. Russ. Phys. Chem. Soc. 1905, 37, 643.
  3. ^ Faworsky, A. Y. (1913). "Über die Einwirkung von Phosphorhalogenverbindungen auf Ketone, Bromketone und Ketonalkohole". J. Prakt. Chem. (in German). 88 (1): 641–698. doi:10.1002/prac.19130880148. 
  4. ^ Cope, Arthur (1960). Organic Reaction Volume XI (1 ed.). New York: Wiley-Interscience. doi:10.1002/jps.2600500225. ISBN 9780471171270. 
  5. ^ Wohllebe, J.; Garbisch, E. W. (1977). "Ring Contraction via a Favorskii-Type Rearrangement: Cycloundecanone". Organic Syntheses. 56: 107. doi:10.15227/orgsyn.056.0107. ; Collective Volume, 6, p. 368 
  6. ^ Shioiri, Takayuki; Kawai, Nobutaka (1978). "New methods and reagents in organic synthesis. 2. A facile conversion of alkyl aryl ketones to α-arylalkanoic acids using diphenyl phosphorazidate. Its application to a new synthesis of ibuprofen and naproxen, nonsteroidal antiinflammatory agents". J. Org. Chem. 43 (14): 2936–2938. doi:10.1021/jo00408a049. 
  7. ^ Hamada, Yasumasa; Shioiri, Takayuki (1982). "Cycloundecanecarboxylic Acid". Organic Syntheses. 62: 191. doi:10.15227/orgsyn.062.0191. ; Collective Volume, 7, p. 135 
  8. ^ Goheen, D. W.; Vaughan, W. R. (1963). "Cyclopentanecarboxylic acid, methyl ester". Organic Syntheses. 39: 37. doi:10.15227/orgsyn.039.0037. ; Collective Volume, 4, p. 594 
  9. ^ Wallach, O. (1918). "Zur Kenntnis der Terpene und der ätherischen Öle. Über das Verhalten zweifach gebromter hexacyclischer Ketone in Abhängigkeit von der Stellung der Bromatome". Justus Liebigs Ann. Chem. (in German). 414 (3): 271–296. doi:10.1002/jlac.19184140303. 
  10. ^ Wallach, O. (1918). "Zur Kenntnis der Terpene und der ätherischen Öle". Justus Liebigs Ann. Chem. (in German). 414 (3): 296–366. doi:10.1002/jlac.19184140304. 
  11. ^ Park, Chan-Ho; Givens, Richard S. (1997). "New Photoactivated Protecting Groups. 6. p-Hydroxyphenacyl: A Phototrigger for Chemical and Biochemical Probes". J. Am. Chem. Soc. 119 (10): 2453–2463. doi:10.1021/ja9635589. 
  12. ^ Givens, Richard S.; Heger, Dominik; Hellrung, Bruno; Kamdzhilov, Yavor; Mac, Marek; Conrad, Peter G.; Cope, Elizabeth; Lee, Jong I.; Mata-Segreda, Julio F.; Schowen, Richard L.; Wirz, Jakob (2008). "The Photo-Favorskii Reaction of p-Hydroxyphenacyl Compounds is Initiated by Water-Assisted, Adiabatic Extrusion of a Triplet Biradical". J. Am. Chem. Soc. 130 (11): 3307–3309. doi:10.1021/ja7109579.