Nucleophilic conjugate addition
Reaction mechanismConjugate addition is the vinylogous counterpart of direct nucleophilic addition. A nucleophile reacts with a α,β-unsaturated carbonyl compound in the β position. The negative charge carried by the nucleophile is now delocalized in the alkoxide anion and the α carbon carbanion by resonance. Protonation leads through Keto-enol tautomerism to the saturated carbonyl compound. In vicinal difunctionalization the proton is replaced by another electrophile.
- Conjugated carbonyls react with secondary amines to form 3-aminocarbonyls (3-ketoamines). For example, the conjugate addition of methylamine to 2-cyclohexenone gives the compound 3-(N-methylamino)-cyclohexanone.
- Conjugated carbonyls react with hydrogen cyanide to 1,4-keto-nitriles. See hydrocyanation of unsaturated carbonyls. In the Nagata reaction the cyanide source is diethylaluminum cyanide.
- The Gilman reagent is an effective nucleophile for 1,4-additions to conjugated carbonyls.
- The Michael reaction involves conjugate additions of enolates to conjugated carbonyls.
- The Stork enamine reaction involves the conjugate addition of enamines to conjugated carbonyls.