deprotonation of ketones with LDA to make enolates

deprotonation of ketones with LDA to make enolates


Hello from Chem Help ASAP. Let’s see how we use LDA to make enolates
from ketones. [turn page]
We have two reactions on the screen. The top one is how we make LDA. The bottom one is how we use LDA to make an
enolate. OK, when chemists use LDA, they can’t just
pull a bottle of LDA from the stockroom. LDA is made fresh every time it is used. How do you make LDA? Funny you should ask. Our top reaction shows this process. We start with diisopropylamine and treat it
with butyllithium, which most people write as BuLi and many people call “booli” or
“buli”. Butyllithium is a super strong base that deprotonates
diisopropylamine. The conjugate base that’s formed is lithium
diisopropylamide, or LDA. The conjugate acid is butane (from butyllithium),
which just hangs out in the flask. This deprotonation is normally performed in
an etherial solvent like THF (tetrahydrofuran). The solution is normally kept cold, often
0 degrees or lower. The end result of this reaction is a fresh
solution of LDA in THF, which can then be used for making enolates. That brings us to the lower reaction. To make an enolate, we start with a ketone. This ketone needs to have a hydrogen off of
the alpha carbon relative to the carbonyl. This ketone is called an “enolizable ketone”. For example, if we look to the upper right
of the screen, I’ve drawn a ketone. It’s called benzophenone. Benzophenone does not have any hydrogens on
its alpha carbons (the carbons on either side of the carbonyl), so you can’t make an enolate
from benzophenone. This is non-enolizable. Back to our lower reaction, LDA is a strong
base, removes an alpha-proton, and forms an enolate, which is stabilized by resonance
through delocalization of the charge onto the carbonyl oxygen. Final comments. On the bottom right, I am drawing an aldehyde. Aldehydes have this beautiful hydrogen off
the carbonyl. It’s so tempting to think this might be
an acidic proton. It’s not. Do NOT touch this hydrogen. When dealing with carbonyls, the acidic proton
is always on the alpha-carbon. Another point with aldehydes… Enolates of aldehydes are tricky, even with
LDA. Aldehyde carbonyls are so unhindered that
LDA – even bulky LDA – tends to attack the aldehyde instead of removing an alpha-hydrogen. Enolates of aldehydes are possible, but I
personally do not cover them in organic chemistry. When dealing with enolates in reactions, we
will only make ketone enolates. Alright, that’s how we use LDA to make enolates. We don’t need to worry about making LDA. We’ll just put LDA over the arrow as a reagent
for making the enolate from a ketone – just like we see in this bottom reaction.

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