Johnson-Corey-Chaykovsky reaction

The Johnson-Corey-Chaykovsky reaction is a chemical reaction in which a carbonyl is converted to an epoxide by the action of a sulfonium ylide. The reaction can be viewed as a methylene transfer.

The original publication by Johnson in 1961 concerned the reaction of 9-dimethylsulfonium fluorenylide with benzaldehyde. The attempted Wittig reaction failed and a benzalfluorene oxide was obtained instead.Ref|Johnson

Variations

Dimethyloxosulfonium methylide, (CH₃)₂SOCH₂, is known as the Corey-Chaykovsky reagent, or CCR for short. CCR is a sulfoxide-ylide and used as a methylene-transfer reagent. Since it is stable for only short periods, it is typically generated in situ.Ref|CoreyRef|Corey2

Trimethyl sulfoxonium iodide, obtained by reaction of DMSO and methyl iodide, can be reacted with a strong base such as sodium hydride to generate the Corey-Chaykovsky reagent.Ref|OrgSyn1969 An alternative procedure for in situ ylide formation is by reaction of trimethylsulfonium iodide, Me₃SO⁺I^-, and NaHMDS. CCR was first demonstrated with benzophenone as a substrate.

The reaction mechanism for this reaction type consists of nucleophilic addition of the ylide to the carbonyl group. A negative charge is transferred to the oxygen carbonyl anion and because the sulfonium cation is a good leaving group it gets expelled forming the oxirane. In the related Wittig reaction, the formation of the much stronger phosphorus oxygen double bond prevents oxirane formation and instead olefination takes place through a 4-membered cyclic intermediate.

References

# "The Chemistry of Ylids. VI. Dimethylsulfonium Fluorenylide-A Synthesis of Epoxides" A. William Johnson, Robert B. LaCount; "J. Am. Chem. Soc." 1961, "83(2)", 417-423. (DOI|10.1021/ja01463a040)
# "Dimethylsulfoxonium Methylide" E. J. Corey, Michael Chaykovsky; "J. Am. Chem. Soc." 1962, "84(5)", 867-868. (DOI|10.1021/ja00864a040)
# "Dimethyloxosulfonium Methylide ((CH3)2SOCH2) and Dimethylsulfonium Methylide ((CH3)2SCH2). Formation and Application to Organic Synthesis" E. J. Corey, Michael Chaykovsky; "J. Am. Chem. Soc." 1965, "87(6)", 1353-1364. (DOI|10.1021/ja01084a034)
# Corey, E. J.; Chaykovsky, M. "Organic Syntheses", Coll. Vol. 5, p.755 (1973); Vol. 49, p.78 (1969). ( [http://www.orgsyn.org/orgsyn/prep.asp?prep=cv5p0755 Article] )

Further reading

* Myllymäki, Vesa, "Design, synthesis and testing of new chiral sulfide catalysts for the Corey-Chaykovsky reaction" [http://herkules.oulu.fi/isbn9514265718/isbn9514265718.pdf T