Corey-Kim reagent

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-... 

Cook and co-workers have described a Pd-catalyzed domino reaction for the preparation of the quinuclidine subunit common to a variety of alkaloids, e.g., 146 to 147 <07OL1469>. In a separate report from the same group, enantiospecific total synthesis of 6-epi-vellosimine 148 proceeded with judicious use of the Corey-Kim reagent (NCS/N S/CH Ch EtsN) for mild access to the delicate axial aldehyde of 148 from the corresponding alcohol <07OL295>. 

Copper(I) f-butoxide, 122 Copper(I) chloride, 123 Copper(II) chloride, 123 Copper(I) cyanide, 124 Copper(I) iodide, 124-125 CoppeKil) sulfate, 389, 462 Copper(ll) sulfate-Pyridine, 125-126 Corey-Kim reagent. 111, 365 Crown ethers, 99-100,126, 356, 387, 389, 392... 

Methylthiomethyl esters (4, 84-85). These esters can also be prepared by reaction of the triethylammonium salts of carboxylic acids with the Corey-Kim reagent and excess triethylamine initially at —70° and then at 20° for 30 minutes. Yield 80-85%. 

Enamittones. The usual method for conversion of a S-diketone such as 1 results in low yields (10-40%). The reaction is improved considerably by use of the Corey-Kim reagent in the presence of trifluoroacetic acid. Undoubtedly an intermediate sulfonium salt is involved, as in Corey-Kim oxidation (5, 129-130). 

Phenylselenomethyl ketones. The reagent reacts with Grignard reagents to form /8 -hydroxy selenides (2), generally in 80-90% yield. Oxidation of the selenides to the desired phenylselenomethyl ketones (3) proved to be more difficult than anticipated. In the case of saturated alcohols, the Corey-Kim reagent (4, 87-90) is satisfactory. Allylic alcohols are best oxidized with DDQ. 

The first step of the mechanism of the Corey-Kim oxidation is the reaction of dimethylsulfide with A/-chlorosuccinimide to generate the electrophilic active species, S,S-dimethylsuccinimidosulfonium chloride Corey-Kim reagent) via dimethylsulfonium chloride. The sulfonium salt is then attacked by the nucleophilic alcohol to afford an alkoxysulfonium salt. This alkoxysulfonium salt is deprotonated by triethylamine and the desired carbonyl compound is formed. The dimethylsulfide is regenerated, and it is easily removed from the reaction mixture in vacuo. In the odorless Corey-Kim oxidation instead of dimethylsulfide, dodecylmethylsulfide is used. This sulfide lacks the unpleasant odor of DMS due to its low volatility. 

Katayama, S., Fukuda, K., Watanabe, T., Yamauchi, M. Synthesis of 1,3-dicarbonyl compounds by the oxidation of 3-hydroxycarbonyl compounds with Corey-Kim reagent. Synthesis 1988,178-183. 

In a 1972 communication, E. J. Corey and C. U. Kim described the first example of this mild oxidation method and expressed their hope that this discovery would find widespread use.1 The oxidation of 4-ferf-butylcyclohexanol (6) to corresponding ketone 7, for example, was achieved in 97% yield by the in situ generated sulfonium chloride complex 5. This complex is now commonly referred to as the Corey-Kim Reagent. The complex is not stable at temperatures above 0 °C for extended periods of time and its rate of decay over time has been followed by continuous FT-IR.2... 

While a variety of alcohols are excellent substrates for the traditional Corey-Kim oxidation, alcohols capable of forming stabilized carbocations such as allylic and benzylic alcohols can undergo a side-reaction to form alkyl chlorides. In fact, the Corey-Kim reagent and conditions, with slight modification, have been used to convert allylic and benzylic alcohols to their corresponding chlorides in very high yield as shown below.9 Alkyl bromides can also be prepared if AT-bromosuccinimide is used in place of Af-chlorosuccinimide. 

The Corey-Kim conditions have also been applied to 3-hydroxycarbonyl compounds to afford 1,3-dicarbonyls and this variation is curious in that in some cases stable dimethylsulfonium dicarbonylmethylides are isolated which have to be further treated with zinc-acetic acid to afford the desired dicarbonyl product. In 1988, Yamauchi showed that the outcome of the addition of 3-hydroxycarbonyls to the Corey-Kim reagent varied depending upon the C-2 substitution pattern.10 As illustrated by the examples below, if the C-2 position is unsubstituted such as in 38, the dimethylsulfonium dicarbonylmethylide 39 was isolated whereas the desired oxidation product 42 was produced if there was at least one substituent (Rj or R4) present at C-2. Other cases of non-C-2-substituted 3-hydroxycarbonyls furnishing stable dimethylsulfonium methylides and their conversion to die desired diketones have been reported. 

Noting the greater reactivity of the newly formed dicarbonyl products for the Corey-Kim reagent present in excess, the authors propose the following mechanism in which the C-2 of the dicarbonyl enol ether tautomer attacks the electrophilic sulfonium... 

Methylthiomethylation. The Corey-Kim reagent (NCS-dimethyl sulfide) induces cyclization of tryptamine derivatives while introducing a methylthiomethyl group at C-3. An efficient route to physostigmine is based on this process. 

Alternate Names Corey-Kim reagent dimethyl(succinimido)-sulfonuim chloride. 

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