[Babcock_Hall]

We have been trying to follow literature models, including the order of addition, as closely as possible.  However we did communicate with a carbohydrate chemist yesterday who suggested adding TMSOTf before adding the alcohol as an option.  There are a great number of variables to explore.

[rolnor]

Sounds good.

[Babcock_Hall]

You can mix the protected methylglucopyranoside with TMSBr to get the bromo-sugar and then react this with the alcohol+1,1eqv. TEA in DCM.

This is starting to look more attractive, but I have not searched it via SciFinder yet.  One can buy tetra acetyl 1-bromoglycosides, and I found one supplier that is particularly inexpensive.

[rolnor]

That sounds great if you can buy the bromosugar. Its like putting on a MEM-group on a alcohol.
It can be a bit slow because you have bulk but it should be OK. I know people use additives such as silver perchlorate. I think TEA makes a triethylammonium species with MEM-chloride so its a catalyst. Silver triflate could be very effective also for speeding things up. Solvent acetonitrile I think.

[Babcock_Hall]

Rituparna Das and Balaram Mukhopadhyay "Chemical O-Glycosylations: An Overview," ChemistryOpen 2016, 5:401–433.  DOI:10.1002/open.201600043
This is a good review at moderate depth.

[rolnor]

I had 3,5-O-p-Toluylribofuranosyl chloride and dissolved this in MeOH+TEA, I got a very nice yield of the 1-O-Methyl ribofunanoside. The bromosugar is more reactive than chloro.