Lecture Notes: Michael Reaction

Introduction to Michael Reaction

• Michael Reaction: A method of forming carbon-carbon bonds.
• Involves a Michael donor and a Michael acceptor.
• Typical Michael donor: Stabilized enolate.
• Base removes the alpha hydrogen to form an enolate.

Electrophilicity in Michael Reaction

• Alpha-beta unsaturated aldehyde is used.
• Beta carbon and carbonyl carbon are electrophilic.
  • Weak bases tend to attack beta carbon (conjugate addition).
  • Strong bases attack carbonyl carbon (direct addition).

Mechanism of Michael Reaction

• Example: Stabilized enolate (Michael donor) reacts with alpha-beta unsaturated aldehyde (Michael acceptor).
• Enolate ion attacks the beta carbon, forming a new bond.
• Anion intermediate then reacts with a weak acid (e.g., water) to form the final product.
  • Product: Typically a 1,5-dicarbonyl compound.

Example Mechanism

1. Base removes alpha hydrogen, forming enolate.
2. Enolate attacks beta carbon in the Michael acceptor.
3. Count carbon chain to ensure correct structure.
4. Use water to stabilize the product.

Conditions for Favorable Michael Reaction

• Stability of enolate ion affects the reaction pathway.
• pKa values give insight into base strength:
  • Diketone alpha hydrogen: pKa ~9.
  • Acetone: pKa ~20.
  • Water: pKa ~15.7.
• Stronger conjugate acids have weaker conjugate bases.
  • Hydroxide is a strong base compared to enolate ion stabilized by carbonyl groups.

Enhancing Michael Reaction Yields

• Adjust the Michael acceptor to favor beta carbon attack.
  • Use a ketone instead of an aldehyde.
  • Add steric hindrance (e.g., tert-butyl group) to make carbonyl carbon less accessible.
• Favor nucleophilic attack at beta carbon over carbonyl carbon.

Additional Example

• React nitroethane with base, followed by a Michael acceptor, then water.
• Nitroethane's alpha hydrogen is acidic, making it a good Michael donor.
• Nitro group stabilizes the negative charge of the enolate.

Final Product Formation

• Negative charge attacks beta carbon in Michael acceptor.
• Reaction sequence:
  1. Form enolate from nitroethane.
  2. Attack beta carbon.
  3. Form intermediate and stabilize with water.
• Major product involves the incorporation of functional groups, preserving the nitrile and nitro functionalities.