Lecture Notes: Formation of Enolates from Non-Symmetrical Ketones

Introduction

• Discusses formation of enolates from ketones
• Focuses on non-symmetrical ketones and their behavior

Non-Symmetrical Ketone Structure

• Ketone with different groups on each side of the carbonyl
• Right side: methyl group
• Left side: CH2 and an alkyl R group
• Alpha carbons are adjacent to the carbonyl
  • Right side: 3 alpha protons
  • Left side: 2 alpha protons

Base Selection and Reaction Conditions

• Choice of base and reaction conditions influence which alpha proton is removed
• Two main bases discussed: LDA (Lithium diisopropylamide) and Sodium Hydride

LDA (Lithium Diisopropylamide)

• Strong, sterically hindered base
• Prefers less hindered side (right side) due to bulkiness
• Removes proton on right alpha carbon
• Forms kinetic enolate
  • Faster formation
  • Less stable
  • Has a double bond and oxygen with a negative charge

Sodium Hydride

• Source of hydride anions
• Removes proton on left alpha carbon
• Forms thermodynamic enolate
  • More stable
  • More substituted double bond

Kinetic vs. Thermodynamic Enolates

• Kinetic Enolate

  • Forms faster
  • Formed using LDA
  • Less stable, less substituted

• Thermodynamic Enolate

  • More stable
  • Formed using bases like sodium hydride
  • More substituted double bond

Practical Application

• Control of enolate formation through base and conditions
• Example problem: ketone with sodium hydride or LDA
  • Sodium hydride leads to thermodynamic control
  • LDA at low temperatures favors kinetic enolate

Example Analysis

• Identify alpha carbons and protons
• Evaluate substitution level for stability
• Influence of temperature and base sterics on enolate formation

Conclusion

• Control of enolate type through base selection and reaction conditions
• Understanding enolate formation important for strategic organic synthesis