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