Corey-Chaykovsky epoxidation

The Corey-Chaykovsky reaction entails the reaction of a sulfur ylide, either dimethylsulfoxonium methylide (1, Corey s ylide, sometimes known as DMSY) or dimethylsulfonium methylide (2), with electrophile 3 such as carbonyl, olefin, imine, or thiocarbonyl, to offer 4 as the corresponding epoxide, cyclopropane, aziridine, or thiirane. ... 

Epoxidation of aldehydes and ketones is the most profound utility of the Corey-Chaykovsky reaction. As noted in section 1.1.1, for an a,P-unsaturated carbonyl compound, 1 adds preferentially to the olefin to provide the cyclopropane derivative. On the other hand, the more reactive 2 generally undergoes the methylene transfer to the carbonyl, giving rise to the corresponding epoxide. For instance, treatment of P-ionone (26) with 2, derived from trimethylsulfonium chloride and NaOH in the presence of a phase-transfer catalyst Et4BnNCl, gave rise to vinyl epoxide 27 exclusively. ... 

Isolated carbonyls always give epoxides from the Corey-Chaykovsky reaction. Take the aldehyde substrate as an example. Spiro epoxide 30 was produced from the reaction of trisnorsqualene aldehyde 28 (R20 represents the polyene side-chain with 20 carbons) with substituted sulfur ylide 29, prepared in situ from cyclopropyldiphenylsulfonium tetrafluoroborate and KOH. " For the epoxidation of ketones, the Corey-Chaykovsky reaction works well for diaryl- (31), arylalkyl- (32), ... 

The Corey-Chaykovsky reaction incited some applications in medicinal chemistry. During the synthesis of analogs of fluconazole, an azole antifungal agent, treatment of 49 with 1 led to the corresponding epoxide, which was subsequently... 

A weak base such as glycine added to [HMIMjPFg has also been reported to catalyze a Knoevenagel reaction of malononitrile and benzaldehyde 110). A KOH-treated [BMIMjPFg also provides a suitable medium for the Corey-Chaykovsky epoxidation of enones and cyclopropanation of aldehydes using trimethyl sulfonium iodide (///). 

Scheme 6.30 Typical epoxides obtained from the Corey-Chaykovsky epoxidation of aldehydes catalyzed by urea 16.

Also, the reaction pathways of the Corey-Chaykovsky epoxidation reaction have been compared quantum-chemically <1999JOC4596>. As models for one transition state, 1,3-oxathiane compounds such as 52, suitably substituted to allow comparison with experiment (Equation 3), were calculated and these predicted both the absolute stereochemistry of the main product 53 and the distribution of the other stereoisomers, as supported by experimental results. Thus, this theoretical study was able to identify the transition state which proved to be responsible for the stereoselectivity of the catalytic Corey-Chaykovsky epoxidation reaction. 

The reaction of sulfur ylides with aldehydes and ketones was first reported by Johnson in 1961, but is for some reason better known as the Corey-Chaykovsky reaction. The reaction between sulfur ylides and an electrophilic carbon atom of a C=0 gives a betaine intermediate. The favoured reaction path is therefore an internal Sn2 process which furnishes an epoxide with regeneration of the sulfide (Scheme 3.28). 

A short enantiospecific total synthesis of (+)-aphanamol I and II from limonene was achieved and the absolute stereochemistry of I and II established in the laboratory of B. Wickberg. The key steps were a de Mayo photocycloaddition, a Corey-Chaykovsky epoxidation and finally a base-cataiyzed fragmentation of the j,8-epoxyalcohol intermediate. Upon treating the photocycloadduct with dimethylsulfoxonium methylide, only the endo epoxide diastereomer was formed due to the steric hindrance provided by the methyl and isopropyl groups. 

The conversion of a bicyclo[2.2.1]octenone derivative to the corresponding bicyclo[3.3.0]octenone, a common intermediate in the total synthesis of several iridoid monoterpenes, was achieved by N.C. Chang et al. The target was obtained by sequential application of the Corey-Chaykovsky epoxidation, Demjanov rearrangement and a photochemical [1,3]-acyl shift. 

In the laboratory of J. Mulzer, the total synthesis of laulimalide, a microtubule stabilizing antitumor agent, was accomplished. The C9 stereochemistry of the natural product was introduced using the Jacobsen HKR on a diastereomeric mixture of a terminal epoxide. The epoxide mixture was prepared via the Corey-Chaykovsky epoxidation of citronellal. The HKR proceeded in high yield and high selectivity at room temperature, and the products were easily separated by flash chromatography. The did was converted into the diastereomerically pure epoxide in three steps. 

Corey-Chaykovsky epoxidation Preparation of epoxides from aldehydes and ketones. 102... 

Ng, J. S. Epoxide formation from aldehydes and ketones - a modified method for preparing the Corey-Chaykovsky reagents. Synth. Commun. 1990, 20,1193-1202. 

Related reactions Corey-Chaykovsky epoxidation and cyclopropanation ... 

Methylenation While cyclic ketones undergo Corey-Chaykovsky reaction to deliver epoxides at room temperature, excess amounts of base suppress the transformation and at high temperature the ketones are converted into 1,2-dimethylenecycloalkanes. 

The synthesis of triticonazole is only described in patents as a one-pot sequence [57] Knoevenagel condensation of 4-chlorobenzaldehyde on 2,2-dimethylcyclopentanone gives the a,) -unsaturated ketone, which enters a Corey-Chaykovsky epoxidation reaction to afford the epoxide which in turn is opened with the potassium salt of 1,2,4-triazole (Scheme 17.10). 

The synthesis scheme is described in two process patents [70] Dieckmann condensation applied to ethyl adipate leads to the salt of 2-ethoxycarbonylcyclopenta-none (Scheme 17.12). From this compound, methylation at position 2 followed by a rearrangement under basic medium brings the methyl group to position 5. The salt obtained is directly benzylated with 4-chlorobenzyl chloride. A second methylation then occurs directly at position 5 and a subsequent decarboxylation allows access to the key carbonyl cyclopentanone with all the required substituents present. The last step consists of a one-pot Corey-Chaykovsky epoxidation reaction in which are successively added to the triazolyl sodium formed in situ, the cyclopentanone and the trimethylsulfoxonium bromide. 

Other references related to the Corey-Chaykovsky epoxidation are cited in the literature. 

Corey-Chaykovsky epoxidation—additive oxidation Cyclopropanation [(1 + 2) + (1 + 2)]... 

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