Ace Your Next Organic Chemistry

With the MOC Membership

Join Here

The Nucleophile Adds Twice (to the ester)

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