Sulfonium-based oxidation of alcohols to aldehydes
Sulfonium-based oxidations of alcohols to aldehydes summarizes a group of organic reactions that transform a primary alcohol to the corresponding aldehyde. Selective oxidation of alcohols to aldehydes requires circumventing over-oxidation to the carboxylic acid. One popular approach are methods that proceed through intermediate alkoxysulfonium species as detailed here. Since most of these methods employ dimethylsulfoxide as oxidant and generate dimethylsulfide, these are often colloquially summarized as DMSO-oxidations. Conceptually, generating an aldehyde and dimethylsulfide from an alcohol and DMSO requires a dehydrating agent for removal of H2O, ideally an electrophile simultaneously activating DMSO. In contrast, methods generating the sulfonium intermediate from dimethylsulfide do not require a dehydrating agent. Closely related are oxidations mediated by dimethyl selenoxide and by dimethyl selenide.
Comparison with related methods
In comparisons, sulfonium-based methods are popular because reactions are efficient, reaction conditions are mild, reactions are operationally simple 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=-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
- chromium reagents
- ruthenium oxides
- oxoammonium species
- transfer hydrogenation or hydride transfer
- MnO2, Barium manganate, 2,3-Dichloro-5,6-dicyano-1,4-benzoquinone for allylic alcohols
Categories
The sulfonium oxidations can be categorized into two groups: The methods discovered earliest rely on activated alcohols like alkyl tosylates or alkyl chloroformates that react as electrophiles when treated with DMSO, liberating an oxygenated leaving group. 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. 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 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 likeand also includes Albright-Goldman, Albright-Onodera, TFAA/DMSO and Me2S/Cl2. Recently, SO2F2 has been proposed for generating the activated sulfoxide from DMSO.