Michael addition
Summary
A Michael addition is the conjugate (1,4) addition of a nucleophile, usually a stabilized enolate, to the β carbon of an α,β-unsaturated carbonyl, forming a new C–C bond. Test point: attack is at the β carbon, not the carbonyl carbon, though strong nucleophiles can add 1,2.
Detail
Meaning: A Michael addition is the conjugate (1,4) addition of a nucleophile (the Michael donor) to an α,β-unsaturated carbonyl (the Michael acceptor). The carbonyl pulls electron density through resonance, so the β carbon carries partial positive charge and is electrophilic. The nucleophile bonds there, the C=C electrons shift onto the oxygen to give an enolate, and protonation gives the saturated carbonyl. Common donors are stabilized enolates from β-diketones or malonate esters. An enolate donor plus an enone acceptor gives a 1,5-dicarbonyl product.
On the MCAT: A passage shows an enone, a base, and an enolate precursor. You may be asked for the product, which carbon is attacked, or why the β carbon is electrophilic (draw the resonance form). Michael addition is also the first step of the Robinson annulation: Michael addition, then intramolecular aldol condensation, builds a new six-membered ring.
Common confusion: Students attack the carbonyl carbon (1,2-addition) by habit. Both modes exist. Softer, resonance-stabilized nucleophiles such as enolates, Gilman reagents, amines and thiols usually add 1,4. Very reactive nucleophiles such as Grignard and organolithium reagents often add 1,2. The 1,4 product keeps the strong C=O and loses a weaker C=C, which favors it thermodynamically.
Sources
- Organic Chemistry (Clayden)
- Organic Chemistry (Wade)
- Organic Chemistry (McMurry)
Written for the MCAT and checked before it was published. For study reference only. Spotted an error? Let us know.