sulfonium-based oxidation of alcohols to aldehydes

In comparisons, sulfonium-based methods are popular because reactions are efficient (high yields, comparably fast, no over-oxidation, few side reactions, reproducible results), reaction conditions are mild (low temperature, no strong acids or bases), reactions are operationally simple (no specialized equipment or uncommon and/or costly reagents necessary, byproducts often easily separated, tolerant of oxygen and moisture,) and they generally avoid highly toxic starting materials and toxic waste disposal. However, the reactions are not too popular with many undergraduate chemistry students in the laboratory since the common byproduct dimethylsulfide is a strong odorant, reminiscent of fouling eggs, that requires a well-ventilated fume hood. Other drawbacks might include excess of base, handling of the dehydrating agent, limited choice of solvent or side reactions at elevated temperature, e.g. Pummerer rearrangement or elimination of the sulfonium intermediate to the reactive H₂C=(S+)-CH₃-species that form methylthiomethyl ethers with alcohols. In consequence this means that the activity of the oxidation can not be tuned at will by increasing the reaction temperature, e.g. to force oxidation of an unreactive alcohol.

Common alternatives to these sulfonium-based methods are oxidations with

• hypervalent iodine (e.g., Dess-Martin periodinane, 2-Iodoxybenzoic acid)
• chromium reagents (e.g., Pyridinium chlorochromate, Collins reagent)
• ruthenium oxides (e.g., Tetrapropylammonium perruthenate)
• oxoammonium species (e.g., TEMPO)
• transfer hydrogenation or hydride transfer (e.g., Oppenauer oxidation)
• MnO₂, Barium manganate, 2,3-Dichloro-5,6-dicyano-1,4-benzoquinone for allylic alcohols

The sulfonium oxidations can be categorized into two groups: The methods discovered earliest rely on activated alcohols like alkyl tosylates (Kornblum oxidation){{cite journal|last=Kornblum|first=N.|author2=Jones, W. J.|author3=Anderson, G. J.|year=1959|title=A new and selective method of oxidation. The conversion of alkyl halides and alkyl tosylates to aldehydes|journal=J. Am. Chem. Soc.|volume=81|issue=15|pages=4113–4114|doi=10.1021/ja01524a080}} or alkyl chloroformates (from reaction of alcohols with phosgene: Barton-Kornblum){{cite journal|last=Barton|first=D. H. R.|author2=Garner, B. J.|author3=Whightman, R. H.|year=1964|title=A New Procedure for the Oxidation of Alcohols|journal=J. Chem. Soc.|pages=1855–1857|doi=10.1039/JR9640001847}} that react as electrophiles when treated with DMSO, liberating an oxygenated leaving group (e.g. {{chem|OTs−}}). However, the additional step for pre-activation of the alcohol and sometimes harsh reaction conditions for the nucleophilic displacement proved less convenient. Therefore, methods generating activated sulfoxides have been developed later. Depicted below is the activated sulfoxide generated during Swern oxidation 4 reacting with a secondary alcohol 5 to form alkoxysulfonium species 6. File:Swern Oxidation Mechanism.png These activated sulfoxides react as electrophiles when treated with an alcohol, expelling a leaving group that might simultaneously function as counter-ion to the alkoxysulfonium species ({{chem|RO−SMe|2|+}}) generated. Upon deprotonation – usually assisted by a mild base like triethylamine – the alkoxysulfonium species decomposes, yielding the aldehyde and dimethylsulfide. The latter collection contains popular oxidations like

• Swern,
• Corey-Kim,
• Parikh-Doering,
• Pfitzner-Moffatt

and also includes Albright-Goldman, Albright-Onodera (DMSO/P₂O₅), TFAA/DMSO (Swern) and Me₂S/Cl₂. Recently, SO₂F₂ has been proposed for generating the activated sulfoxide from DMSO.{{cite journal|last=Zha|first=G.-F.|author2=Fang, W.-Y.|author3=Leng, J.|author4=Qin, H.-L.|year=2019|title=A Simple, Mild and General Oxidation of Alcohols to Aldehydes or Ketones by SO₂F₂/K₂CO₂ Using DMSO as Solvent and Oxidant|journal=Adv. Synth. Catal.|volume=361|issue=10|pages=2262–2267|doi=10.1002/adsc.201900104}}

• Alcohol oxidation
• Oxidation with chromium(VI)-amine complexes
• Oxoammonium-catalyzed oxidation
• Dess–Martin oxidation

{{reflist}}

Category:Organic oxidation reactions