Reactions Corey-Chaykovsky

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.  

In 1962, Corey and Chaykovsky described the generation and synthetic utility of 

Similar to phosphur ylides, sulfur ylides 1 and 2 possess the nucleophilic site at the carbon atom and the pendant leaving group at the heteroatom (sulfur). Different from the Wittig reaction, the Corey-Chaykovsky reaction does not lead to olefins. 

Sulfur ylides 1 and 2 are usually prepared by treatment of either trimethylsulfoxonium 

In addition, NaOMe, and NaNH2, have also been employed. Applieation of phase-transfer conditions with tetra-n-butylammonium iodide showed marked improvement for the epoxide formation. Furthermore, many complex substituted sulfur ylides have been synthesized and utilized. For instance, stabilized ylide 20 was prepared and treated with a-D-a/lo-pyranoside 19 to furnish a-D-cyclopropanyl-pyranoside 21. Other examples of substituted sulfur ylides include 22-25, among which aminosulfoxonium ylide 25, sometimes known as Johnson s ylide, belongs to another category. The aminosulfoxonium ylides possess the configurational stability and thermal stability not enjoyed by the sulfonium and sulfoxonium ylides, thereby are more suitable for asymmetric synthesis. 

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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... 

In addition to the synthesis of heterocycles, the Corey-Chaykovsky reaction bestows an entry to carbocycles as well. The reaction of (trialkylsilyl)vinylketene 89 with substituted ylide 90 led exclusively to rrans-4,5-dimethyl cyclopentenone 91. The substituted ylide 90 here serves as a nucleophilic carbenoid reagent in the formal [4 +1] annulation reaction. 

Notably, some substrates possess enough steric bias to exert sterospecificity for the Bucherer-Bergs reaction. For instance, ketone 21, derived from enone 20 via a Corey-Chaykovsky reaction, underwent a Bucherer-Bergs reaction to fashion spirohydantoin 22 as a single isomer. 

Organometallic betaines of type I can be considered as the closest structural analogs of carbon betaines of the (+ )P-C-C-X( ) type (IV), which were regarded for a long time as possible intermediates in classical reactions of carbonyl and thiocarbonyl compounds with phosphorus ylides (Wittig and Corey-Chaykovsky reactions and related processes,5,6 Scheme 1). Vedejs and coworkers7,8 proved unambiguously that oxapho-sphetanes (III) are true intermediates in the reactions of nonstabilized phosphorus ylides with carbonyl compounds. The formation of oxabetaines (+)p-c-c-o(-> was detected only in the form of their adducts with lithium salts.9,10... 

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). 

Aziridines can also be synthesized enantioselectively from imines and alkyl halides using a camphor-derived chiral sulfide mediator 640 in a one-pot procedure via the imino Corey-Chaykovsky reaction. Thus, benzyl bromide 641 and tosyl imine 642 provide aziridine 643 in practically quantitative yield as a 3 1 mixture of ( /Z)-isomers and in 92% ee ((i4)-isomer) (Scheme 157). An electron-withdrawing substituent on the imine nitrogen is necessary to activate the 7t-system for nucleophilic attack <2001TL5451>. 

The most commonly used reagents to effect the addition of a methylene group to an aldehyde or ketone are sulfur ylides such as dimethylsulfonium methylide (1) or dimethyloxosulfonium methylide (2) (Corey-Chaykovsky reaction). This reaction is well reviewed in standard treatises of organic synthesis - and several useful monographs. - This update will concentrate on progress attained from 1975. The reader is also encouraged to consult reviews on the chemistry of the related sulfoximine-derived ylides such as (3). -"... 

Salto, T., Sakairi, M., Akiba, D. Enantioselective synthesis of aziridines from imines and alkyl halides using a camphor-derived chiral sulfide mediator via the imino Corey-Chaykovsky reaction. Tetrahedron Lett. 2001,42, 5451-5454. 

Volatron, F., Eisenstein, O. Wittig versus Corey-Chaykovsky Reaction. Theoretical study of the reactivity of phosphonium methylide and sulfonium methylide with formaldehyde. J. Am. Chem. Soc. 1987, 109, 1-4. 

Das, G. K. Substituent effect on transition structure of Corey-Chaykovsky reaction a semiempirical study. Indian J. Chem., Sect. A Inorg., Bio-inorg., Phys., Theor. Anal. Chem. 2001, 40A, 23-29. 

Ohno, F., Kawashima, T., Okazaki, R. Synthesis, Crystal Structure, and Thermolysis of a Pentacoordinate 1,2> 6-Oxathietane An Intermediate of the Corey-Chaykovsky Reaction of Oxosulfonium Ylides J. Am. Chem. Soc. 1996, 118, 697-698. 

Lindvall, M. K., Koskinen, A. M. P. Origins of Stereoselectivity in the Corey-Chaykovsky Reaction. Insights from Quantum Chemistry. J. 

In the case of the sulfur analogues, the reaction of sulfiir ylides with carbonyl compounds, known as the Corey-Chaykovsky reaction, is a well-established procedure for the synthesis of oxiranes This reaction is usually considered to involve the formation of an a/ift -betaine (205) followed by a back side attack of an oxido anion on the p-carbon. (Scheme 3.29)... 

Meyers and coworkers [327, 1494] have applied the Corey-Chaykovsky reaction to chiral bicyclic lactams 1.92. The face selectivity of the reaction of CH2=S(0)Me2 with this Michael acceptor depends upon the nature of the angular substituent R When R1 = H, the cyclopropane is introduced selectively on the exo... 

The corresponding stable sulfurane oxide 71 was prepared by the oxidation of 72 with raCPBA in the presence of Na2HP04, as shown in Scheme 34 [74] and Fig. 6. The molecular structure of 71 was also determined by X-ray crystallography. In contrast, the thermolysis of 71 gave the corresponding oxirane 73 in almost quantitative yield, but the expected olefin was not obtained at all. These results suggest that 1,2-oxathietane derivatives are in fact the intermediates of Corey-Chaykovsky reaction of the sulfonium and oxosulfonium ylids. 

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. 

Methylene insertion o-Hydroxydiaryl ketones give 3-aiylbenzofurans, which are apparently derived from a normal Corey-Chaykovsky reaction. Additionally, insertion of a CH2 group between the carbonyl and one of the aryl residues also occurs. 

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