LDA
/ ell-dee-AY /
LDA stands for lithium diisopropylamide, a base that is the workhorse of enolate chemistry. Its structure is a nitrogen carrying a negative charge with a lithium counterion, flanked by two bulky isopropyl groups: (i-Pr)2N(minus) Li(plus). It is made on the spot by treating diisopropylamine with butyllithium. The two big isopropyl groups crowd the nitrogen, and that bulkiness is the whole point.
LDA has three properties that make it ideal for forming enolates. First, it is a very strong base — its conjugate acid, diisopropylamine, has a pKa around 36, far higher than a ketone's alpha-hydrogen (~20), so LDA deprotonates the carbonyl essentially completely and irreversibly. Second, it is too bulky to act as a nucleophile; it will pluck off a proton but will not itself add to the carbonyl carbon, so you make the enolate cleanly without competing addition. Third, that same bulk steers it toward the less hindered alpha-proton, giving the kinetic enolate.
Why does this matter? Mild bases like hydroxide or alkoxide only partially deprotonate a simple ketone, leaving an equilibrium with lots of unreacted ketone around — which causes problems like self-condensation and over-reaction. LDA, used cold (typically -78 C) in an aprotic solvent like THF, converts the ketone fully and quickly to a single, well-defined enolate before you add the electrophile. That clean, complete, regioselective enolate is exactly what directed alkylations and crossed aldol reactions need.
To alkylate a ketone cleanly: add the ketone to LDA in THF at -78 C to form the kinetic lithium enolate completely, then add the alkyl halide. Using NaOH instead would leave most of the ketone unreacted and invite side reactions.
LDA: strong enough to fully deprotonate, too bulky to add — the ideal enolate base.
LDA is the tool for COMPLETE, irreversible deprotonation of a weakly acidic ketone. For doubly-activated substrates (malonic/acetoacetic esters, pKa ~11), a mild alkoxide already deprotonates fully, so LDA is unnecessary there.