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Aldol Reactions and 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.

Fig.3
Reactions of α,β-unsaturated carbonyl compounds with extremely strong nucleophiles.
Hint
In other words, soft bases tend to add to the β carbon (1,4-addition), while hard bases tend to attack the carbonyl carbon (1,2-addition) of α,β-unsaturated carbonyl compounds.

Exercise

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