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Also known as: Conjugate Addition, 1,4-Addition
Discovered by Arthur Michael (1887)
Conjugate (1,4-) addition of a stabilized nucleophile (Michael donor) to an α,β-unsaturated carbonyl (Michael acceptor). The nucleophile adds to the β-carbon rather than the carbonyl carbon, giving a 1,5-dicarbonyl relationship.
Enolate formation: Base deprotonates the Michael donor (malonate, acetoacetate, or ketone) to form the nucleophilic enolate.
Conjugate addition: The enolate attacks the β-carbon (not the carbonyl C) of the α,β-unsaturated carbonyl, forming an enolate intermediate.
1,4-addition (to β-carbon), not 1,2-addition (to C=O)
Protonation of the enolate intermediate gives the 1,5-dicarbonyl product.
Diethyl malonate + Methyl vinyl ketone
NaOEt, EtOH
Diethyl 2-(3-oxobutyl)malonate
Acetoacetic ester + Acrylonitrile
NaOEt, EtOH
2-Acetyl-4-cyanoglutarate
Powerful C-C bond-forming reaction. The 1,5-dicarbonyl products are ideal for further cyclization (Robinson annulation). Extremely common in total synthesis.