[KevinChristopher]

EDIT: I can't post the pictures. Even through the file sizes are appropriate, the site crashes every time.

Hey everyone! I am thinking about how to approach this problem & figured I would reach out since I am new to peptide synthesis (I am primarily a materials chemist).I have a large molecule with lots of alcohols, primary amides, secondary amides and one carboxylic acid. The carboxylic acid is where I wish to perform the transformation. I wish to take the carboxylic acid and convert it to a ketone with a small carbon chain that contains a carboxylic acid at the end of it. I have some ideas but here are my main issues:

Organolithiums are great for converting carboxylic acids to ketones. However, the large molecule contains lots of acidic protons, these groups would need to be protected or deprotonated before adding the organolithium component. Another issue, on the organolithium would be an ester and I would expect the organolithium to not be compatible with this! The reason I have the ester is so I can convert it to the carboxylic acid on the final molecule. I know organolithiums are more selective for carboxylic acids than esters but I don't know if a molecule containing an ester and an organolithium would be stable enough to be introduced to the large molecule. My instinct says no. Maybe make the organolithium in situ with the large molecule? Assuming I took the proper precautions with the acidic protons on the large molecule, which doesn't look like a great task in the first place. I guess I could use sodium amide to remove the acidic protons on the alcohols and amides? If you organic savvy people have any advice, it would be appreciated. I HATE posting this with no pictures but maybe someone will be able to decipher.  Thank you!

[Borek]

Posting random file to test.

Edit: definitely works.

Site "crashes" or displays a message that the image can't be posted?

[Borek]

Sadly, this kind of error can be on your side, on our side, or even somewhere in between. Can you try another browser?

[KevinChristopher]

I jumped through some hoops but after trial and error looks like I finally got it!

-Molecule on the first attachment is the large molecule.

-Molecule at the top of the second image is the transformation I wish perform. "R" is the large molecule from the first image.

-The bottom of the second image is a transformation route I had in mind but i see the ester and the organolithium as highly problematic. Maybe if i produce it in situ with the large molecule after removing the necessary acidic protons from the large molecule? It seems like a stretch through.