Corey-Kim

Nakagawa devised a concise synthetic route to physostigimine (169) where the key step involves the alkylative cyclization of 1,3-dimethylindole (167) with (Z)-aziridine catalyzed by Sc(OTf)3 and TMSC1 to give 168, which, in turn, can be converted into 169 . A similar asymmetric approach to this natural product was also developed by these authors via treatment of tryptophan carbamates with the Corey-Kim reagent so as to induce intramolecular cyclization to the pyrrolo-indole skeleton . 

Oxidation of p-hydroxy ketones. Reaction of the Corey-Kim reagent with these substrates can result in dimethylsulfonium dicarbonylmethylides in 80-98% yield. These S-ylides are desulfurized to p-diketones by zinc in acetic acid, p-... 

The IR, NMR, and NMR spectra of this material are identical with those for distilled geranyl chloride (bp 49-51 C at 0.2 mm). Distillation on a small scale significantly reduces the yield, and there is no improvement in the yield of the phosphorylation reaction using distilled material. A synthesis of geranyl chloride was reported earlier in this series. We find, however, that the procedure of Corey, Kim, and Takeda is more convenient. 

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... 

In fact, Corey-Kim conditions offer a good method for the regioselec-tive transformation of allylic and benzylic alcohols into chlorides, in the presence of other alcohols.252 The use of A-bromosuccinimide in spite of /V-chIorosuccini mide, quite expectedly, allows the preparation of allylic and benzylic bromides. It must be mentioned that when the transformation of alcohols into chlorides is desired, the activated alcohol is allowed to decompose in the absence of triethylamine whereas, when an oxidation is desired, triethylamine must be added as soon as the alcohol is activated. That is why, some benzylic alcohols can be efficiently oxidized under Corey Kim conditions,253 while others can be transformed into benzylic bromides with NBS and Me2S.252... 

The Corey Kim procedure is the oxidation method of choice for the transformation of (3-hydroxycarbonyl compounds into 1,3-dicarbonyl compounds. Treatment of (3-hydroxycarbonyl compounds under Corey Kim conditions leads to an intermediate 1,3-dicarbonyl compound 33 that reacts in situ with activated DMSO, resulting in the generation of a stable sulfur ylide 34. This sulfur compound can be transformed into the desired 1,3-dicarbonyl compound by reduction with zinc in acetic acid.254... 

General Procedure for Oxidation of Alcohols Using Corey-Kim Method... 

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. 

Similar to other Moffatt oxidations, the Corey-Kim method results sometimes in the generation of methylthiomethyl ethers by reaction of alcohols with H2C=S(+)-Me, resulting from decomposition of activated DMSO.259... 

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... 

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