Favorskii rearrangement

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Not to be confused with Favorskii reaction.

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 is principally a rearrangement of

α-halo ketones that 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 usually 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]

The Favorskii rearrangement
The Favorskii rearrangement

History

The reaction is named for the Russian chemist

Alexei Yevgrafovich Favorskii[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.

Favorskii rearrangement mechanism
Favorskii rearrangement mechanism

The second step has also been proposed to be stepwise process, with chloride anion leaving first to produce a zwitterionic oxyallyl cation before a disrotatory electrocyclic ring closure takes place to afford the cyclopropanone intermediate.[9]

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

When enolate formation is impossible, the Favorskii rearrangement takes place by an alternate mechanism, in which addition to hydroxide to the ketone takes place, followed by concerted collapse of the tetrahedral intermediate and migration of the neighboring carbon with displacement of the halide. This is sometimes known as the pseudo-Favorskii rearrangement, although previous to labeling studies, it was thought that all Favorskii rearrangements proceeded through this mechanism.

An animation of the reaction mechanism of the Favorskii rearrangement
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[10][11]

Photo-Favorskii reaction

The reaction type also exists as a

dione spiro intermediate (4) although the latter has thus far eluded detection.[13]

Photo Favorskii Givens 2008

See also

  • Syntheses of cubane proceed by Favorskii rearrangements:[14]
Steps in one synthesis of cubane.

References

  1. ISBN 9780471171270
    .
  2. doi:10.15227/orgsyn.056.0107
    ; Collected Volumes, vol. 6, p. 368.
  3. doi:10.1021/jo00408a049
    .
  4. doi:10.15227/orgsyn.062.0191
    ; Collected Volumes, vol. 7, p. 135.
  5. doi:10.15227/orgsyn.039.0037
    ; Collected Volumes, vol. 4, p. 594.
  6. Favorskii, A. E. (1894). J. Russ. Phys. Chem. Soc. 26: 590. {{cite journal}}: Missing or empty |title= (help
    )
  7. Favorskii, A. E. (1905). J. Russ. Phys. Chem. Soc. 37: 643. {{cite journal}}: Missing or empty |title= (help
    )
  8. doi:10.1002/prac.19130880148
    .
  9. ISSN 0036-021X
    .
  10. doi:10.1002/jlac.19184140303
    .
  11. doi:10.1002/jlac.19184140304
    .
  12. doi:10.1021/ja9635589
    .
  13. PMID 18290649
    .
  14. ^ Eaton, Philip E.; Cole, Thomas W. (1964). "Cubane". J. Am. Chem. Soc. 86 (15): 3157–3158. doi:10.1021/ja01069a041.

Further reading

  • Chenier, Philip J. (1978). "Favorskii rearrangement in bridged polycyclic compounds". Journal of Chemical Education. 55 (5): 286.
    doi:10.1021/ed055p286
    .
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