Alkylation with LDA (kinetic enolate): practice and mechanism
LDA is a bulky, very strong base. At −78 °C it quickly removes the H from the less substituted α-side (kinetic enolate). Methylation happens there.
Example
LDA is a very strong, bulky base. At −78 °C it quickly and irreversibly removes the most accessible α H, at the less substituted α carbon (kinetic enolate). Methyl iodide alkylates exactly there.
Mechanism step by step
- 1
LDA at −78 °C quickly and irreversibly removes the most accessible α-H: kinetic enolate.
- 2
In the cold there is no equilibration to the more stable, more substituted enolate.
- 3
The enolate attacks CH₃I via SN2: the methyl group goes to the less substituted α-position.
Practice tasks
Which product forms, which reagent is needed? After each answer you see the explanation.
Which main product forms?
Typical mistakes
- The more substituted (thermodynamic) enolate forms with small bases at higher temperature. LDA in the cold deprotonates the less hindered side.
- In a methyl ketone the CH₃ group is the less hindered side. The bulky LDA removes the proton there, not from the CH₂.
Often confused with: α-Bromination of ketones (acidic) · Acetoacetic ester synthesis
Frequently asked questions
Kinetic or thermodynamic enolate?
Kinetic: bulky strong base (LDA), −78 °C, short time → less substituted. Thermodynamic: smaller base (NaOEt, NaH), room temperature, equilibrium → more substituted.
Why must LDA deprotonate completely?
Otherwise the enolate reacts with leftover ketone (aldol reaction). LDA (pKa of diisopropylamine ≈ 36) deprotonates the ketone (≈ 20) quantitatively.