Base-promoted formation of enolates from ketones
Description: When ketones (or aldehydes) are treated with strong base, they form their conjugate bases, called enolates.
Notes: Enolates are excellent nucleophiles and are used in many important reactions, such as the Aldol, Claisen, Michael, and many other reactions.
Notes: A base such as NaOH is strong, but not strong enough to irreversibly deprotonate an aldehyde or ketone. Thus the enolate that is formed is in equilibrium with the aldehyde or ketone (example 1). If the ketone is non-symmetrical and has two different carbons which can be deprotonated, a mixture of enolates will form (example 2). To avoid this, the strong bulky base lithium di-isopropyl amide (LDA) can be used to irreversibly deprotonate the less hindered side of the ketone (example 3). In addition to aldehydes and ketones, the enolates of esters can also be formed (example 4).
Example 5 shows an application of enolate formation, in the alkylation of enolates
Mechanism: Strong base simply removes a proton from the carbon adjacent to the carbonyl (the “alpha carbon”) (Step 1, arrows A and B). This results in the conjugate base (the “enolate”) which is resonance stabilized.
Notes: Note here that LDA preferentially removes the proton from the less hindered alpha carbon.