[Guitarmaniac86]

I am trying to find the pKa of the proton shown for the compound in the attachment but so far I am unable to. Initially I was trying to do an aldol condensation with formaldehyde on the ribose acetonide with pot carb, however, this reaction has not worked at all. I then attempted to formylate the 2-position after protecting the 5' hydroxy, but this reaction is not working either. I have an idea to do it from the lactone, but I dont know the exact pKa of the proton shown and hence, what base would be ideal. I suspect the pKa for the proton to be between 7 - 12 after consulting pKa tables for lactones, but because I cannot find data for this proton specifically, I am making a big assumption. However, based on this assumption, I am tempted to set up a series of reactions on small scale using different organic bases.

I would like opinions on the bases to use. I am probably going to do five 50 mg reactions simultaneously and monitor the reactions by TLC and NMR with the following bases:

-Pot carb because I have been using it (following a paper) and it will give me a good baseline to compare data
-Triethylamine
-DIPEA (will have to modify a prep to suite the reaction I think)
-Pyridine (I dont think this will work)
-LDA (I think this might be overkill)

If anyone has any advice it would be greatly appreciated. I am trying to save my PhD and I am in panic mode (I still have two years left with no hope of finishing it seems).

[sjb]

I am trying to find the pKa of the proton shown for the compound in the attachment but so far I am unable to. Initially I was trying to do an aldol condensation with formaldehyde on the ribose acetonide with pot carb, however, this reaction has not worked at all. I then attempted to formylate the 2-position after protecting the 5' hydroxy, but this reaction is not working either. I have an idea to do it from the lactone, but I dont know the exact pKa of the proton shown and hence, what base would be ideal. I suspect the pKa for the proton to be between 7 - 12 after consulting pKa tables for lactones, but because I cannot find data for this proton specifically, I am making a big assumption. However, based on this assumption, I am tempted to set up a series of reactions on small scale using different organic bases.

I would like opinions on the bases to use. I am probably going to do five 50 mg reactions simultaneously and monitor the reactions by TLC and NMR with the following bases:

-Pot carb because I have been using it (following a paper) and it will give me a good baseline to compare data
-Triethylamine
-DIPEA (will have to modify a prep to suite the reaction I think)
-Pyridine (I dont think this will work)
-LDA (I think this might be overkill)

If anyone has any advice it would be greatly appreciated. I am trying to save my PhD and I am in panic mode (I still have two years left with no hope of finishing it seems).

I think a pKa of 7-12 might be a bit low, looking at Evans' tables for ketones, has a pKa of ~23, for instance

[clarkstill]

Yeah I'd guess a pKa in the low 20s... I think the LDA will work fine, but the rest will be unreactive.  Maybe LiHMDS, to tone the LDA down a little? Or tert-butoxide?

Good luck... aldols to generate quaternary centres can be tricky!