The Nucleophile Adds Twice (to the ester)

by Kiley Lynch

With ketones and aldehydes, things were pretty simple. Nucleophiles added to them (remember: the “addition” mechanism), we add acid, and things stopped there. Two steps: Addition, then protonation

With esters, reaction mechanisms are going to become a little longer. But hopefully not much more complex.

It’s all going to come back to the two key mechanisms in carbonyl chemistry: addition, and elimination.

  • With addition, the rate depends on how electron-poor (electrophilic) is the carbonyl carbon.
  • With elimination, the rate depends on leaving group ability – the weaker the base, the better the leaving group. 

Let’s focus on elimination today – and compare the reactions of Grignards with aldehydes and esters.

The first step in both reactions is the same: addition.

But the two products after the first step are different.

  • In both cases we have an O(-).
  • In the case of the aldehyde, every other group on the carbon is now H or R – and H(-) and R(-) are both terrible leaving groups, much stronger bases than O(-).
  • (Remember: we never start with a weak base and have a much stronger base as a leaving group)
  • In the case of the ester, we also have an OR. And RO(-) is comparable in base strength to O(-), which makes it a plausible leaving group. 

And that’s what happens next: elimination. This means we make a new ketone, which can then perform a second addition. Now, we’re at the same point we were when we added a Grignard to the aldehyde: no good leaving groups. So it sits there until we add acid.

Addition – Elimination – Addition – Protonation

It’s the same mechanism as that for addition of LiAlH4 to esters. Here’s a little graphic comparing the two.


 

Tomorrow: let’s talk about some other addition-elimination reactions.
Thanks for reading! James