Question

What is the advantage of alkylating using enamines instead of the enolate counterpart?

Answer 1

The most important advantages are:

• Enamines are neutral, but enolates are deprotonated, making enamines less prone to over-reaction (i.e. adding more than one alkyl group by accident). We like more control over our reactants.
• Enamines are experimentally easier to prepare since with enolates, you have to force an irreversible reaction using something like lithiumdiisopropyl amide (LDA), but with enamines you don't. (If you use `"OH"^(-)` on a carbonyl compound, the equilibrium is not heavily skewed towards the enolate.)

Enamines are typically made using a Stork reaction, where you react a carbonyl compound with something like pyrrolidine, piperidine, or morpholine, in the presence of acid. I will use pyrrolidine on acetone as an example.

As you can see here, this enamine has nice steric hindrance that inhibits the amount of substitution reactions that the enamine can undergo, making it less reactive.

Now, let's just compare side-by-side how enamines function vs. enolates for alkylation to sum it up.