15.37:
Conjugate Addition of Enolates: Michael Addition
Recall conjugate addition in an α,β-unsaturated carbonyl compound where the nucleophile adds to the β carbon of the C=C bond.
Michael addition is a type of conjugate addition involving nucleophiles containing activated methylene flanked by electron-withdrawing groups.
The reaction is catalyzed by a base that deprotonates the acidic methylene proton. This generates a doubly-stabilized enolate ion that serves as the nucleophile or the Michael donor on account of its lone pair.
Compounds comprising a methylene group with two adjoining electron-withdrawing substituents are effective Michael donors compared to normal enolates with a single electron-withdrawing neighbor.
The enolate attacks the β carbon of the α,β-unsaturated carbonyl compound. This conjugated system acts as the electrophile or the Michael acceptor.
The resulting compound has a new C–C σ bond, which, upon subsequent protonation, gives the Michael-addition product.
15.37:
Conjugate Addition of Enolates: Michael Addition
The attack of a nucleophile at the β carbon of an α,β-unsaturated carbonyl compound is called conjugate addition. Conjugate addition reactions of active methylene compounds, such as β-diketones, β-keto esters, β-keto nitriles, and α-nitro ketones, are called Michael addition reactions.
The reaction is catalyzed by a base that abstracts the acidic methylene hydrogen, generating a doubly-stabilized enolate ion that serves as the nucleophile or the Michael donor. The base employed depends on the nature and strength of the electron-withdrawing group in the nucleophile.
The enolate attacks the β carbon of the conjugated system, which acts as the electrophile or the Michael acceptor. These molecules contain double bonds in conjugation with carbonyl, cyano, or nitro groups. Following the nucleophilic attack, a new C–C bond results in the formation of another enolate ion.
Finally, protonation of the enolate, either by the solvent or the starting substrate, gives the Michael-addition product.
