Pummerer rearrangement

Aside from acetic anhydride, trifluoroacetic anhydride and trifluoromethanesulfonic anhydride have been employed as activators.{{cite journal|last1=Smith|first1=Laura H. S.|last2=Coote|first2=Susannah C.|last3=Sneddon|first3=Helen F.|last4=Procter|first4=David J.|title=Beyond the Pummerer Reaction: Recent Developments in Thionium Ion Chemistry|journal=Angewandte Chemie International Edition |volume=49|issue=34|pages=5832–44|date=2010|pmid=20583014|doi=10.1002/anie.201000517|url=https://www.research.manchester.ac.uk/portal/en/publications/beyond-the-pummerer-reaction-recent-developments-in-thionium-ion-chemistry(eb5e930f-6150-4c8b-8187-ef253b10aa2d).html}} Common nucleophiles besides acetates are arenes, alkenes, amides, and phenols.

The usage of α-acyl sulfoxides and Lewis acids, such as TiCl₄ and SnCl₄, allow the reaction to proceed at lower temperatures (0 °C).{{cite journal|last=Stamos|first=Ioannis K. |journal=Tetrahedron Letters|date=1986|volume=27|issue=51|pages= 6261–6262|doi=10.1016/S0040-4039(00)85447-7|title=Arylation of α-phosphoryl sulfides via their pummerer rearrangement intermediates generated from the corresponding sulfoxides}}

Thionyl chloride can be used in place of acetic anhydride to trigger the elimination for forming the electrophilic intermediate and supplying chloride as the nucleophile to give an α-chloro-thioether:{{cite journal|last1=Kosugi |first1=Hiroshi |last2=Watanabe |first2=Yasuyuki |last3=Uda |first3=Hisashi |title=Lewis Acid-Mediated Carbon-Carbon bond forming reaction using the Pummerer Rearrangement Products from Chiral beta-Hydroxy Sulfoxides|journal=Chemistry Letters |volume=18 | issue=10 |date=1989 |pages=1865–1868 |doi=10.1246/cl.1989.1865}}

Image:Pummerer Ex ThionylChloride.png

Other anhydrides and acyl halides can give similar products. Inorganic acids can also give this reaction. This product can be converted to aldehyde or ketone by hydrolysis.{{cite journal | last1 = Meffre | first1 = Patrick | last2 = Durand | first2 = Philippe | last3 = Le Goffic | first3 = François | title = Methyl (S)-2-phthalimido-4-methylthiobutanoate | journal = Organic Syntheses | volume = 76 | page = 123 | date = 1999 | doi = 10.15227/orgsyn.076.0123 }}

The mechanism of the Pummerer rearrangement begins with the acylation of the sulfoxide (resonance structures 1 and 2) by acetic anhydride to give 3, with acetate as byproduct. The acetate then acts as a catalyst to induce an elimination reaction to produce the cationic-thial structure 4, with acetic acid as byproduct. Finally, acetate attacks the thial to give the final product 5.

Image:Pummerer Rearrangement Mechanism.png

The activated thial electrophile can be trapped by various intramolecular and intermolecular nucleophiles to form carbon–carbon bonds and carbon–heteroatom bonds.

The intermediate is so electrophilic that even neutral nucleophiles can be used, including aromatic rings with electron donating groups such as 1,3-benzodioxole:{{cite journal | last1 = Ishibashi | first1 = Hiroyuki| first2 = Yumiko | last2 = Miki | first3 = Yoshiaki | last3 = Ikeda | first4 = Akiko | last4 = Kiriyama | first5 = Masazumi | last5 = Ikeda | journal = Biological & Pharmaceutical Bulletin | date = 1989 | volume = 37 | issue = 12| pages = 3396–3398 | doi = 10.1248/cpb.37.3396 | title = Synthesis of α-(Methylthio)arylacetamides and Their Conversion into Some Biologically Active Arylethylamines | doi-access = free }}

Image:Pummerer Ex Veratrole.png

It is possible to perform the rearrangement using selenium in the place of sulfur.{{Cite journal | last1 = Gilmour | first1 = Ryan | last2 = Prior | first2 = Timothy J. | last3 = Burton | first3 = Jonathan W. | last4 = Holmes | first4 = Andrew B. | title = An organocatalytic approach to the core of eunicellin | doi = 10.1039/B709322E | journal = Chemical Communications | issue = 38 | pages = 3954–6 | date = 2007 | pmid = 17896044}}

When a substituent on the α position can form a stable carbocation, this group rather than the α-hydrogen atom will eliminate in the intermediate step. This variation is called a Pummerer fragmentation.{{cite journal|title=Pummerer fragmentation vs. Pummerer rearrangement: a mechanistic analysis | first1 = Benoît |last1 = Laleu | first2 = Marco | last2 = Santarém Machado | first3 = Jérôme | last3 = Lacour|journal= Chemical Communications|issue= 26|date = 25 May 2006 | pages = 2786–2788| doi=10.1039/b605187a| pmid = 17009463 }} This reaction type is demonstrated below with a set of sulfoxides and trifluoroacetic anhydride (TFAA):

Image:PummererFragmentation.png

The organic group "R2" shown in the diagram above on the bottom right is the methyl violet carbocation, whose pK_R+ of 9.4 is not sufficient to out-compete loss of H⁺ and therefore a classical Pummerer rearrangement occurs. The reaction on the left is a fragmentation because the leaving group with pK_R+ = 23.7 is particularly stable.

The reaction was discovered by {{Interlanguage link|Rudolf Pummerer|de}}, who reported it in 1909.{{cite journal|last=Pummerer|first=Rudolph |title=Über Phenyl-sulfoxyessigsäure|journal=Chemische Berichte|date=1909|volume=42|issue=2|pages= 2282–2291|doi=10.1002/cber.190904202126|url=https://zenodo.org/record/1426341 }}{{cite journal|last=Pummerer|first=Rudolph |title=Über Phenylsulfoxy-essigsäure. (II.)|journal=Chemische Berichte|date=1910|volume=43|issue=2|pages= 1401–1412|doi=10.1002/cber.19100430241|url=https://zenodo.org/record/1426409 }}

• Organosulfur chemistry
• Polonovski reaction ― similar reaction involving an amine oxide
• Boekelheide reaction ― similar reaction involving a pyridine oxide

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{{DEFAULTSORT:Pummerer Rearrangement}}

Category:Rearrangement reactions

Category:Name reactions