Corey- Kim oxidation

Corey and Kim described an oxidation,6a in which activated DMSO is not generated by activation of DMSO, but by oxidation of dimethyl sulfide. Although, they described only the use of chlorine and /V-chlorosuccinimidc as dimethyl sulfide oxidants, we propose that the name Corey-Kim oxidations be applied to alcohol oxidations, in which activated DMSO is generated by oxidation of dimethyl sulfide, regardless of the oxidant employed. 

In most Moffatt oxidations, activated DMSO is prepared by the activation of DMSO in a reaction with an electrophile. On the other hand, in a Corey-Kim oxidation, no DMSO is used in the preparation of activated DMSO , which is obtained by oxidation of dimethyl sulfide. 

As operation with gaseous chlorine is dangerous and inconvenient, Corey Kim oxidations are normally performed by oxidation of dimethyl sulfide with /V-chIorosuccinimide rather than with chlorine. This results in the formation of a different kind of active DMSO species, in which a sulfur-nitrogen bond is present. 

Interestingly, it is possible to employ diisopropyl sulfide in the place of dimethyl sulfide in Corey-Kim oxidations, in which case primary alcohols can be oxidized in the presence of secondary ones or vice versa, depending on reaction temperature.250... 

Sometimes, better yields are obtained in Corey-Kim oxidations by using methyl phenyl sulfide in the place of dimethylsulfide, a result that can be related with the greater solubility of the sulfoxonium intermediate.251... 

Although the Corey-Kim oxidation is not used as often as the Swern oxidation—probably because of the bad odour of dimethyl sulfide—it offers the advantage of allowing an operation above -25°C. Typically, NCS (A-chlorosuccinimide) and Me2S are mixed in toluene at 0°C, resulting in the formation of a precipitate of activated DMSO. The reaction mixture is cooled to ca. —25°C and the alcohol is added for activation. This is followed by addition of Et3N and allowing the reaction to reach room temperature. 

As in other Moffatt oxidations, a Corey-Kim oxidation may produce minor amounts of methylthiomethyl ethers. These can be minimized by using a solvent of low polarity, like toluene.248a Nonetheless, very often dichloromethane is used, because of its better solubilizing power. Almost always triethylamine is used as base. 

Because of the high temperature employed in the activation of the alcohols, the Corey-Kim oxidation is not suitable for the oxidation of alcohols, derived from radicals able to stabilize carbocations—particularly allylic and dibenzylic alcohols. In such cases, the activated alcohol is attacked by the chloride anion, resulting in the formation of organic chlorides.248a... 

This oxidation on an apparently very simple substrate fails with PCC, PDC, DCC-DMSO and (F3C-C0)20-DMS0, because of the high sensitivity of the selenium atom to suffer oxidation. On the other hand, a Corey-Kim oxidation delivers a 60% of... 

Functional Group and Protecting Group Sensitivity to Corey-Kim Oxidations... 

As the Corey-Kim oxidation is carried out under almost neutral conditions at low temperature, most functional and protecting groups are expected to remain unaffected. As this method did not find exhaustive use in organic synthesis, no ample data are yet available. 

Interestingly, when a Corey-Kim oxidation (Me2S/NCS) is performed with diisopropyl sulfide, instead of dimethyl sulfide, primary alcohols are selectively oxidized at 0°C, while lowering the temperature to —78°C causes the selective oxidation of secondary alcohols.34... 

Some standard alcohol oxidants that may not have been originally devised for selective oxidations are able, in favourable substrates, to oxidize secondary alcohols in the presence of primary ones.1 Thus, cases are known in which Corey-Kim oxidation,2 TFAA-activated DMSO,lb Collins reagent2 or PDClb show a certain preference for the oxidation of secondary alcohols. 

A classical Corey-Kim oxidation sometimes shows a certain preference for the oxidation of secondary alcohols.2 Additionally, a Corey-Kim oxidation, in which diisopropyl sulfide is employed in the place of dimethyl sulfide, presents a preference for the oxidation of primary alcohols at 0°C and secondary alcohols at -78°C.50... 

The Corey-Kim Oxidation allows the synthesis of aldehydes and ketones from primary alcohols and secondary alcohols, respectively. 

The variation of the Swern oxidation is the Corey-Kim oxidation Treatment of DMS (Me2S) with CI2 or N-chlorosuccinimide (NCS) forms dimethylchlorosulfonium ion (A), which reacts with alcohol to form sulfoxonium complex B. Treatment of sulfoxo-nium complex B with a base Et3N gives the corresponding aldehyde or ketone via ylide C (Scheme 7.8). 

Because of the foul smell of DMS, several odourless versions of Corey-Kim and Swern oxidations have been reported. For example, odourless dodecyl methyl sulfide (Dod-S-Me) is an alternative to DMS in Corey-Kim oxidations. 

---