[Babcock_Hall]

Although I began to discuss this reaction on another thread, I think it is better to start a new topic, to focus on the particulars of this chemistry.  We ran a reaction using TBSOTf/lutidine on a β-aromatic glucoside with the intention of adding four TBDMS groups.  There were two similar protocols in the literature, but we did not strictly follow either one (it ended up being hybrid between the two).  We did not know which spot corresponded to our product by TLC, and because we were unsure whether or not the reaction had gone to completion, we added more of our silylation reagents than one protocol indicated, moving from about 1.5 TBDMSOTf per -OH group to about 2.0.  We washed with aqueous HCl and other aqueous solutions, and we ran a silica gel column using 7% ether in hexanes.

Our product is not pure; in our three pools of fractions, there was only modest separation between what appears to be our product and a colored impurity.  The impurity has strong signals near 0.85 ppm and 0.00 ppm, and the ratio of the two peaks is about 3:2.  Its identity is not yet clear to us, although it would seem to be a derivative from unreacted TBDMSOTf.  We think we can get better separation with a less aggressive mobile phase, and we can also examine other systems.  If we had the reaction to do over again, we would strongly consider adding a copper sulfate wash step.  I am not sure whether HCl or copper sulfate is better at removing lutidine.  Does anyone have any comments on the probable identity of the impurity or on other things we should try?

[Babcock_Hall]

To follow up, we tried staining with PMA and a second spot showed up on our plate, one that was faint under UV light.  We think that by backing off the percentage of ether in the mobile phase, we have a shot at separating our product.

[Babcock_Hall]

https://www.chemicalforums.com/index.php?topic=108042.0

The link above goes back to the first thread on silylation that I mentioned in the opening post.  Because the first thread was a more general discussion of silylation, I started the present thread, but I regret this approach if it was confusing.  Today we ran a column with a lower percentage of diethyl ether.  We are not yet certain that the column worked, but the indications are good.  One major compound eluted quite quickly, and the compound of interest (on the basis of a spot test for a functional group that was present) eluted well behind it.

As an aside, we had some anomalies with following this reaction by TLC.  I think that the problem was that some of the diethyl ether evaporated from the TLC chamber, causing an anomalously low R_f values.  It is entirely possible that our choice of conditions for the first column suffered from the same discrepancy.  Everything eluted from the column much more quickly than we expected that it would.  This problem might be ameliorated by using MTBE, which is slightly less volatile.  Or we could use the freshest possible solvent in the TLC chamber.