:Favorskii rearrangement

The reaction is named for the Russian chemist Alexei Yevgrafovich Favorskii.{{cite journal | last1 = Favorskii | first1 = A. E. | author-link = Alexei Yevgrafovich Favorskii | year = 1894 | journal = J. Russ. Phys. Chem. Soc. | volume = 26 | page = 590 | title = none }}{{cite journal | last1 = Favorskii | first1 = A. E. | author-link = Alexei Yevgrafovich Favorskii | year = 1905 | journal = J. Russ. Phys. Chem. Soc. | volume = 37 | page = 643 | title = none }}{{cite journal|author-link = Alexei Yevgrafovich Favorskii|first = A. Y.|last = Faworsky|title = Über die Einwirkung von Phosphorhalogenverbindungen auf Ketone, Bromketone und Ketonalkohole|journal = J. Prakt. Chem.|year = 1913|volume = 88|issue = 1|pages = 641–698|doi = 10.1002/prac.19130880148|language = de|url = https://zenodo.org/record/1428054}}

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. Its formation can otherwise be viewed as a 2-electron electrocyclization of a 1,3-dipole, which can be captured in Diels Alder reactions. The cyclopropanone intermediate is opened to yield the more stable carbanion, which is quickly protonated.{{Cite book |last=Kurti 1 Czako 2 |first=Laszlo 1 Barbara 2 |title=Strategic Applications of Named Reactions in Organic Synthesis |date=15 September 2005 |publisher=Elsevier |isbn=0-12-429785-4 |pages=164–165}}

File:Favorskii rearrangement.png

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.{{Cite journal|last1=Akhrem|first1=A A|last2=Ustynyuk|first2=T K|last3=Titov|first3=Yu A|date=1970-09-30|title=The Favorskii Rearrangement|journal=Russian Chemical Reviews|volume=39|issue=9|pages=732–746|doi=10.1070/rc1970v039n09abeh002019|bibcode=1970RuCRv..39..732A|issn=0036-021X}}

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 or quazi-Favorskii rearrangement, although previous to labeling studies, it was thought that all Favorskii rearrangements proceeded through this mechanism.

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{{cite journal|title = Zur Kenntnis der Terpene und der ätherischen Öle. Über das Verhalten zweifach gebromter hexacyclischer Ketone in Abhängigkeit von der Stellung der Bromatome|journal = Justus Liebigs Ann. Chem.|language = de|volume = 414|issue = 3|pages = 271–296|first = O.|last = Wallach|author-link = Otto Wallach|year = 1918|doi = 10.1002/jlac.19184140303|url = https://zenodo.org/record/1427647}}{{cite journal|title = Zur Kenntnis der Terpene und der ätherischen Öle|language = de|first = O.|last = Wallach|author-link = Otto Wallach|journal = Justus Liebigs Ann. Chem.|volume = 414|issue = 3|pages = 296–366|year = 1918|doi = 10.1002/jlac.19184140304|url = https://zenodo.org/record/1427599}}

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 p-hydroxyphenacyl groups.{{cite journal|title = New Photoactivated Protecting Groups. 6. p-Hydroxyphenacyl: A Phototrigger for Chemical and Biochemical Probes|first1 = Chan-Ho|last1 = Park|first2 = Richard S.|last2 = Givens|journal = J. Am. Chem. Soc.|year = 1997|volume = 119|issue = 10|pages = 2453–2463|doi = 10.1021/ja9635589}} The deprotection proceeds through a triplet diradical (3) and a dione spiro intermediate (4) although the latter has thus far eluded detection.{{cite journal|title = The Photo-Favorskii Reaction of p-Hydroxyphenacyl Compounds is Initiated by Water-Assisted, Adiabatic Extrusion of a Triplet Biradical|first1 = Richard S.|last1 = Givens|first2 = Dominik|last2 = Heger|first3 = Bruno|last3 = Hellrung|first4 = Yavor|last4 = Kamdzhilov|first5 = Marek|last5 = Mac|first6 = Peter G.|last6 = Conrad|first7 = Elizabeth|last7 = Cope|first8 = Jong I.|last8 = Lee|first9 = Julio F.|last9 = Mata-Segreda|first10 = Richard L.|last10 = Schowen|first11 = Jakob|last11 = Wirz|journal = J. Am. Chem. Soc.|year = 2008|volume = 130|issue = 11|pages = 3307–3309|doi = 10.1021/ja7109579|pmc = 3739295|pmid=18290649}}

:Image:PhotoFavorskiiGivens2008.svg

• Syntheses of cubane proceed by Favorskii rearrangements:Eaton, Philip E.; Cole, Thomas W. (1964). "Cubane". [http://J.%20Am.%20Chem.%20Soc. J. Am. Chem. Soc.] 86 (15): 3157–3158. [https://doi.org/10.1021%2Fja01069a041 doi:10.1021/ja01069a041].

:File:Cuban3.svg

• 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

{{Reflist}}

• {{cite journal |doi=10.1021/ed055p286|title=Favorskii rearrangement in bridged polycyclic compounds|year=1978|last1=Chenier|first1=Philip J.|journal=Journal of Chemical Education|volume=55|issue=5|page=286|bibcode=1978JChEd..55..286C}}

Category:Rearrangement reactions

Category:Name reactions

Category:Ring contraction reactions