Favorskii rearrangement

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Not to be confused with Favorskii reaction. ‹See Tfd›

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 Favorski 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]

In the case of cylic α-halo ketones, the rearrangement occurs as depicted below:[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.

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. ^ Favorskii, A. E. J. Prakt. Chem. 1913, 88, 658.
  4. ^ Kende, A. S. Org. React. 1960, 11, 261–316. (Review)
  5. ^ Organic Syntheses, Coll. Vol. 6, p.368 (1988); Vol. 56, p.107 (1977). (Article)
  6. ^ Shioiri, T.; Kawai, N. J. Org. Chem. 1978, 43, 2936.
  7. ^ Organic Syntheses, Coll. Vol. 7, p.135 (1990); Vol. 62, p.191 (1984). (Article)
  8. ^ Organic Syntheses, Coll. Vol. 4, p.594 (1963); Vol. 39, p.37 (1959). (Article)
  9. ^ Zur Kenntnis der Terpene und der ätherischen Öle. Über das Verhalten zweifach gebromter hexacyclischer Ketone in Abhängigkeit von der Stellung der Bromatome Justus Liebig's Annalen der Chemie Volume 414, Issue 3 , Pages 271 – 296 O. Wallach 1918 doi:10.1002/jlac.19184140303
  10. ^ Zur Kenntnis der Terpene und der ätherischen Öle (pp. 296–366) O. Wallach Justus Liebig's Annalen der ChemieVolume 414, Issue 3 , pp. 296–366 1918 doi:10.1002/jlac.19184140304
  11. ^ New Photoactivated Protecting Groups. 6. p-Hydroxyphenacyl: A Phototrigger for Chemical and Biochemical Probes Chan-Ho Park and Richard S. Givens J. Am. Chem. Soc.; 1997; 119(10) pp 2453–63; (Article) doi:10.1021/ja9635589
  12. ^ The Photo-Favorskii Reaction of p-Hydroxyphenacyl Compounds Is Initiated by Water-Assisted, Adiabatic Extrusion of a Triplet Biradical Richard S. Givens, Dominik Heger, Bruno Hellrung, Yavor Kamdzhilov, Marek Mac, Peter G. Conrad, II, Elizabeth Cope, Jong I. Lee, Julio F. Mata-Segreda, Richard L. Schowen and Jakob Wirz J. AM. CHEM. SOC. 2008, 130, 3307–09 doi:10.1021/ja7109579