Alpha Carbon Reactions

Conjugate Addition

When an alpha,beta-unsaturated carbonyl reacts with a nucleophile, either 1,2 addition (simple addition) or 1,4 addition (conjugate addition) occurs. A 1,4 addition of an enolate is referred to as a Michael reaction.

A conjugate addition (or 1,4-addition) is a reaction in which a nucleophile reacts with an alpha,beta-unsaturated carbonyl compound in the beta position. For conjugate addition, alpha,beta-unsaturated carbonyls can be prepared using a halogenation reaction on the alpha carbon of the carbonyl, followed by the addition of a weak base (commonly pyridine) to form a double bond. Nucleophiles that are strong bases (for example, Grignard and organolithiums) attack the carbonyl group by 1,2 addition (simple addition) in an irreversible reaction. Nucleophiles that are weaker bases tend to react at the beta carbon of the C=C {\rm{C{=}C}} through 1,4 addition (conjugate addition) in a rapid, though reversible, reaction.

The Michael reaction (or Michael addition) is a 1,4-addition reaction in which a carbanion is added to an alpha,beta-unsaturated carbonyl compound. The Michael reaction involves the nucleophilic addition of a carbanion to an alpha,beta-unsaturated carbonyl, and it is used to form CC {\rm{C{-}C}} bonds.

Michael Reaction

The Michael reaction occurs when a stabilized enolate attacks the beta carbon. The attacking nucleophile is called the Michael donor, and the alpha,beta-unsaturated group is called the Michael acceptor.
The Robinson annulation is a reaction in which a Michael reaction is followed by an intramolecular aldol condensation to form a cyclohexenone ring. The formation of cyclohexenone rings is important for the synthesis of natural products such as antibiotics. The Robinson annulation is named for Sir Robert Robinson, the 1947 Nobel Prize winner in chemistry.

Robinson Annulation

The Robinson annulation involves a Michael reaction, a 1,4-addition of an enolate, followed by an intramolecular aldol condensation to produce a cyclohexenone.