Johnson–Corey–Chaykovsky reaction

Johnson–Corey–Chaykovsky reaction is a series of chemical reactions used in organic chemistry to synthesize epoxides, cyclopropanes, and other cyclic compounds from aldehydes, ketones, and imines through the use of sulfonium ylides. It was independently discovered by William S. Johnson and Elias James Corey with Michael Chaykovsky in the 1960s. This reaction is notable for its ability to form three-membered rings with high stereoselectivity.

Mechanism

The Johnson–Corey–Chaykovsky reaction involves the generation of a sulfonium ylide from a sulfonium salt. The ylide then undergoes a nucleophilic addition to a carbonyl compound (aldehyde or ketone) or an imine to form an intermediate which quickly undergoes a cycloaddition to form the cyclic product. The choice of sulfonium ylide determines the size of the ring formed. For example, using dimethylsulfonium methylide typically leads to the formation of epoxides, while using higher-order ylides can lead to the formation of cyclopropanes or larger rings.

Applications

The Johnson–Corey–Chaykovsky reaction has been widely applied in the synthesis of complex natural products and in the development of pharmaceuticals. Its ability to efficiently construct three-membered rings makes it a valuable tool in the synthesis of epoxides and cyclopropanes, which are common motifs in bioactive molecules.

Variants

Several variants of the Johnson–Corey–Chaykovsky reaction have been developed to expand its utility. These include the use of different sulfonium ylides, the application to various substrates beyond aldehydes and ketones, and modifications to the reaction conditions to improve yield and selectivity.

Limitations

While the Johnson–Corey–Chaykovsky reaction is a powerful synthetic tool, it does have limitations. The reaction conditions can be sensitive to the nature of the substrate, and the generation of the sulfonium ylide requires careful handling due to its reactivity. Additionally, the reaction may not always proceed with high diastereoselectivity, particularly when applied to complex molecules.

See also

• Epoxide
• Cyclopropane
• Sulfonium
• Ylide
• Stereochemistry