Lecture Notes on Enolate Formation

Overview

• Discussion on the formation of enolates from ketones.
• Focus on unsymmetrical ketones.
• Consideration of base choice and reaction conditions affecting enolate formation.

Definitions

• Alpha Carbon: The carbon adjacent to the carbonyl group.
• Alpha Protons: Protons attached to the alpha carbon.

Enolate Formation

1. Symmetrical vs. Unsymmetrical Ketones

   • Symmetrical ketones have identical alkyl groups on both sides.
   • Unsymmetrical ketones have different groups on each side, affecting enolate formation.

2. Base Selection and Reaction Conditions

   • Strong, Sterically Hindered Base (e.g., LDA)
     • Prefers the less hindered alpha proton.
     • Forms the kinetic enolate.
   • Less Sterically Hindered Base (e.g., NaH, KH)
     • Forms the thermodynamic enolate by taking a more hindered proton.

Kinetic vs. Thermodynamic Enolate

• Kinetic Enolate

  • Forms faster.
  • Predominantly from less hindered side.
  • Favored by strong, bulky bases like LDA at low temperatures.
  • Less stable, less substituted double bond.

• Thermodynamic Enolate

  • More stable, forms more slowly.
  • Favored by hydride anions (e.g., NaH, KH).
  • Forms under higher temperatures and non-hindered conditions.
  • More substituted double bond.

Stability of Enolates

• Double Bond Substitution
  • More substituted double bonds are more stable.
  • Thermodynamic enolate is better substituted, hence more stable than kinetic enolate.

Practical Application

• By choosing the appropriate base and controlling temperature, one can selectively form either the kinetic or thermodynamic enolate.
• LDA and Cold Temperatures
  • Favors kinetic enolate.
• NaH and Elevated Temperatures
  • Favors thermodynamic enolate.

Summary

• Control over enolate formation can be achieved by altering bases and reaction conditions.
• Understanding the differences between kinetic and thermodynamic enolates is crucial for predicting reaction outcomes.