15.35 : Conjugate Addition to α,β-Unsaturated Carbonyl Compounds

α,β-Unsaturated carbonyl compounds are molecules bearing a carbonyl and alkene functionality in conjugation with each other. The conjugation in the molecule leads to three resonance structures. The hybrid form exhibits two probable electrophilic sites: the carbonyl carbon and the β carbon.

A simple nucleophilic attack at the carbonyl center results in an alkoxy intermediate, which gives the direct or 1,2-addition product upon further protonation.

When the nucleophile attacks the β carbon, it generates an enolate ion intermediate. The protonation of the intermediate results in an enol molecule. Because the addition of hydrogen takes place at the fourth position (counting from the site of nucleophilic attack),the process is called conjugate or 1,4-addition. Finally, the enol tautomerizes to the more stable keto-form.

Addition reactions in α,β-unsaturated carbonyl compounds depend on the nature of the nucleophile. While stronger nucleophiles like lithium aluminum hydride, Grignard reagents, and organolithium compounds favor 1,2-addition;weaker nucleophiles such as organocopper reagents, amines, alcohols, and thiols prefer 1,4-addition.