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silylation and desilylation reviews or information
Babcock_Hall:
Halmos T et al., "STUDIES OF THE SELECTIVE SILYLATION OF METHYL α-D-AND β-D- ALDOHEXOPYROSIDES: STABILITY OF THE PARTIALLY PROTECTED DERIVATIVES IN POLAR SOLVENTS". Carbohydrate Research 170 1987 57-69.
We would like to add four TBDMS groups to an aromatic glucoside. We have an aldehyde group on the aromatic ring. The paper above was mainly concerned with partially silylated derivatives of four methyl glycosides, two glucose, two galactose, and one mannose derivative. Under their condition A (2 mole of imidazole per mole of TBDMSCl in DMF; 24 hours at room temperature), they varied the ratio of TBDMSCl from 2.2 to 3.2 to 4.3 equivalents. When they used 4.3 equivalents, they saw a variable amount of tetrasilylated product, from undetected (apparently both anomers of methyl galactoside) to 5% (the alpha forms of methyl glucopyranoside and methyl mannopyranoside) to 38% (methyl-β-D-glucopyranoside).
This leads to some questions. The first is whether our change from methyl to an aromatic group at C-1 (the anomeric position) will cause the reaction to speed up or slow down (my prediction is that it will not make much difference either way). The second is how to increase the yield of the tetrasilylated product. There are only a few non-patent references I have found so far on the use of TBDMSCl to react with glucosides, but I may have narrowed my search too much. IIRC I focused on TBDMSCl/imidazole-utilizing reactions, because these are the reagents that we purchased.
Two more things. I found a paper (see below) which turned glycosides into trimethylsilyl derivatives, using bis(trimethylsilyl)trifluoroacetamide with 1% TMSCl in pyridine at 60 °C for 30 minutes. It is fair point that the conditions are different, but could it be that the greater bulk of the tert-butyldimethylsilyl group makes it difficult to obtain fully silylated material?
Finally, is N-methyl-N-(tert-butyldimethylsilyl)-trifluoroacetamide a stronger donor of tert-butyldimethylsilyl groups than the silyl chloride? I will do a search for recipes in the next few days.
Isidorov, VA Journal of Chromatography A, 1521 (2017) 161–166. http://dx.doi.org/10.1016/j.chroma.2017.09.033
Babcock_Hall:
In the 1987 paper that I cited, their Method B used catalytic DMAP (8% by mole), along with 2 equivalents of TBDMSCl, and triethylamine was the base. Their method A used a variable number of equivalents of TBDMSCl. I have not yet compared Methods A and B at the same mole ratio of TBDMSCl to methylglycopyranoside.
I also wanted to draw attention to the failure to observe any tetra-silylation with methyl galactopyranosides as substrates. The three substituents on C3 (-OH), C4(-OH), and C5(-CH2OH) are all on the same side of the ring, in contrast to glucopyranosides, where the substituent at C4 is on the opposite side of the ring. This is consistent with a steric problem, although I would hesitate to call it strong evidence.
rolnor:
You can use TBDSOTf its more powerfull. When you want to protect this many groups in close proximity it does not seem ideal to chose such a large PG because if steric bulk. Have you thought of other PG-s? I think SEM can be similar deprotected with fluoride and has similar stability but much less bulk.
M https://pubchem.ncbi.nlm.nih.gov/compound/2-_Trimethylsilyl_ethoxymethyl-chloride
Babcock_Hall:
One possibility is to add DMAP into the standard conditions (TBDMSCl/imidazole). However, I only found one published example, and the results were not impressive. I did another search, and I found several examples where TBDMS-trifluoromethanesulfonate was used in similar reactions.
EDT
Another possibility is to take our chances with trimethylsilyl as the protecting group.
rolnor:
If you want to do stuff like chromatography or wet workup the TMS will not be stable.
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