COREY-KIM Oxidizing Reagent

COREY KIM Oxidizing reagent 79 COREY-WINTERAlkenesynthesis 80 CORNFORTH Rearrangement 81 Crafts 131... 

COREY Oxidizing reagents for alcohols 78 COREY Enantioselective borane reduction 77 COREY Homologatne epaxidation 78 COREY - KIM Oxidizing reagent 79 COREY-WINTERAlkenesynthesis 80 CORNFORTH Rearrangement 81 Crafts 131... 

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). 

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. 

In the last few years fluorous combinatorial chemistry has been extended and augmented by other fluorous techniques developed by analogy with established methods in solid-phase-supported synthesis. Use of fluorous condensation reagents for the Mitsunobu reaction [23] enables easy removal of all condensation reagents except the coupled starting materials after the reaction [24] (Scheme 3.23). A fluorous variant of the Swern [25] and Corey-Kim oxidations [26] enables handling of stoichiometric quantities of malodorous dimethyl sulfide to be avoided [27] (Scheme 3.24). 

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. 

Oxidation of alcohols. This stable reagent, prepared from t-BuNH2 by N,N-dichlorination and then treatment with PhSAc, functions in the same fashion as the reactive species generated in the Swem and Corey-Kim oxidations. With which efficient oxidation of alcohols is performed in dichloromethane in the presence of DBU (11 examples, 90-99%). ... 

Polymeric thioanisole, ( —c HiSCHa. Crosby et al have prepared a polymeric thioanisole reagent from macroreticular polystyrene, (p)-C4H5, and have shown that it can be used in the Corey-Kim oxidation (4, 89) of primary and secondary alcohols. Yields are somewhat lower than those obtained with CI2 — C6H5SCH3. The main advantages of the polymeric reagent are ease of work-up with recovery of the reagent for reuse and freedom from odor. 

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-... 

N-Protected a-amino ketones.1 N-(-Phenylfluorenyl)alaninal (2) is readily converted to a variety of N-PhFl-a-amino ketones (3) by reaction of a Grignard reagent (excess) followed by oxidation with NCS and S(CH3)2 (Corey-Kim re-... 

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. 

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... 

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. 

---