Sulfonium-based oxidations of alcohols to aldehydes summarizes a group of organic reactions that transform a primary alcohol to the corresponding aldehyde (and a secondary alcohol to the corresponding ketone). 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 (RO−SMe+
2X-, e.g. compound 6) as detailed here. Since most of these methods employ dimethylsulfoxide (DMSO) 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.[1]
The sulfonium oxidations can be categorized into two groups: The methods discovered earliest rely on activated alcohols like alkyl tosylates (Kornblum oxidation)[2] or alkyl chloroformates (from reaction of alcohols with phosgene: Barton-Kornblum)[3] that react as electrophiles when treated with DMSO, liberating an oxygenated leaving group (e.g. 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.
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 (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
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.[4]