Aldol-like Reactions Michael reaction

Aldol-like Reactions

Michael reaction

Aldol condensations and aldol-like condensations yield α,β-unsaturated carbonyl compounds.

 As they enable a nucleophilic attack on the polarized double bond, α,β-unsaturated carbonyl compounds are critical starting products in many syntheses. 

A nucleophilic attack on the double bond may be possible because of the double bond's polarization by the carbonyl group and the resonance stabilization of the α carbanion, which is generated by a nucleophilic attack on the β carbon, by conjugation with the carbonyl group. 

The intermediate α carbanion is actually an enolate that is subsequently protonated to the enol. The enol is in equilibrium with the ketone or aldehyde through keto-enol tautomerism.

 All in all, the reaction is a 1,4-addition to an α,β-unsaturated carbonyl compound. It is called Michael reaction (after Arthur Michael).

Fig.1

Michael re­ac­tion.

The original, classical Michael reaction is the addition of an enolate to an α,β-unsaturated carbonyl compound. In this case, the product of a Michael reaction is a 1,5-dicarbonyl compound. However, a variety of further nucleophiles may be applied.

Fig.2

Michael re­ac­tions with dif­fer­ent nu­cle­ophiles

If the nucleophile's nucleophilicity is low, the Michael reaction may occasionally be made possible through acid catalysis.

Theoretically, the Michael acceptor (the α,β-unsaturated carbonyl compound) contains two electrophilic positions, the β carbon and the carbonyl carbon. However, the product of the 1,4-addition usually exceeds the product of the 1,2-addition, as ...

• ... Michael reaction is reversible, and, thus, the thermodynamically more stable product, which contains the strong carbon-oxygen double bond, is favored.
• ... due to the Michael reaction's reversibility, the less stable 1,2-addition product is reconverted into the starting products and consequently into the more stable 1,4-addition product.

If extremely strong nucleophiles, such as hydrides or an alkyllithium compound, are applied to the Michael reaction, the reversibility is restricted. The reaction is then kinetically controlled. As a result, the 1,2-addition exceeds the 1,4-addition.