Favorskii rearrangement

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

In organic chemistry, the Favorskii rearrangement is a reaction of α-halo ketones with a nucleophilic base to acyl derivatives. In the rearrangement, the substrate extrudes the carbonyl carbon to a primary position, which then acylates the base. In the case of cyclic α-halo ketones, the Favorskii rearrangement constitutes a ring contraction:[1]

History

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]

Reaction mechanism

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]

Polyhalogenated substrates

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.

Photo-Favorskii reaction

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]

See also

References

  1. ^ Goheen, D. W.; Vaughan, W. R. (1963). "Cyclopentanecarboxylic acid, methyl ester". Organic Syntheses. 39: 37. doi:10.15227/orgsyn.039.0037; Collected Volumes, vol. 4, p. 594.
  2. ^ Favorskii, A. E. (1894). J. Russ. Phys. Chem. Soc. 26: 590.{{cite journal}}: CS1 maint: untitled periodical (link)
  3. ^ Favorskii, A. E. (1905). J. Russ. Phys. Chem. Soc. 37: 643.{{cite journal}}: CS1 maint: untitled periodical (link)
  4. ^ 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.
  5. ^ Chenier, Philip J. (1978). "Favorskii rearrangement in bridged polycyclic compounds". Journal of Chemical Education. 55 (5): 286. Bibcode:1978JChEd..55..286C. doi:10.1021/ed055p286.
  6. ^ Eaton, Philip E.; Cole, Thomas W. (1964). "Cubane". J. Am. Chem. Soc. 86 (15): 3157–3158. doi:10.1021/ja01069a041.
  7. ^ Akhrem, A A; Ustynyuk, T K; Titov, Yu A (30 September 1970). "The Favorskii Rearrangement". Russian Chemical Reviews. 39 (9): 732–746. Bibcode:1970RuCRv..39..732A. doi:10.1070/rc1970v039n09abeh002019. ISSN 0036-021X.
  8. ^ Kurti 1 Czako 2, Laszlo 1 Barbara 2 (15 September 2005). Strategic Applications of Named Reactions in Organic Synthesis. Elsevier. pp. 164–165. ISBN 0-12-429785-4.{{cite book}}: CS1 maint: numeric names: authors list (link)
  9. ^ a b c Kende, Andrew S. "The Favorskiĭ rearrangement of haloketones". In Cope, Arthur C. (ed.). Organic Reactions. Vol. 11. Wiley. pp. 261–316. doi:10.1002/0471264180.or011.04.
  10. ^ 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.
  11. ^ 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.
  12. ^ Wohllebe, J.; Garbisch, E. W. (1977). "Ring Contraction via a Favorskii-Type Rearrangement: Cycloundecanone". Organic Syntheses. 56: 107. doi:10.15227/orgsyn.056.0107; Collected Volumes, vol. 6, p. 368.
  13. ^ 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.
  14. ^ 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. PMC 3739295. PMID 18290649.
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