Conjugate Addition

Most Nuc can undergo conjugate addition when given the right circumstances.

Conjugate additions can also be called Miachel additions or 1,4 additions

Alkenes are nucleophilic but when conjugated together with another alkene or a carbonyl, they become electrophilic

Both the carbonyl carbon and the beta carbon receive partial positive charges

Conjugate addition reactions have enolates or enols as intermediates

Amines are very good for conjugate addition due to their neutrality and the proton available to attach to the alpha carbon

Often conjugate addition involves acid as it makes the alkene even more nucleophilic

Kinetic product - 1,2 addition, forms faster, hard nucleophiles

Thermodynamic product - 1,4 addition, forms more stable, soft nucleophiles

Conjugate addition reaction speed inverts carbonyl reaction speed

Hard molecules are governed by charges and electrostatic effects

Soft molecules are governed by orbital effects

Hard reacts well with hard and soft with soft

Organocopper reagents undergo conjugate addition

• Reagents: 2 RLi and CuI

• Products: R group

• Regioselectivity: Beta carbon

• Stereoselectivity: None

If there is a good leaving group on the beta carbon, the electrophile will undergo alkene substitution rather than addition, kicking the leaving group. The intermediate will act as an extended tertiary intermediate

Nucleophilic epoxidation

• Reagents: H₂O₂

• Products: Epoxide group

• Regioselectivity: Alpha and beta carbons

• Stereoselectivity: None