Substitute for TBAF in Desilylation of TMS

Why doesn't it react with MeOH to give MeO^- and H2 in a vigorous fashion?

Try HF in acetonitrile.

I have NaF, KF, .
Just wonder if these would work in MeOH:H2O

Another case is that I have tetrabutylammonium bromide. Can I use it together with KF, so the ions are.mixed to make it work?

Quote from:

I am shocked that MeOH/KC₂O₃ works for this! But basically any fluoride source will deprotect TMS.

Yup, very nice, clean, chemoselective, cheap reaction.

Here's an entry on chemspider

http://cssp.chemspider.com/article.aspx?id=100

I never bothered with anhydrous MeOH. In fact it is a bit odd that in that entry they claim to have distilled the MeOH over CaH₂ - I would have thought MeOH reacts with CaH₂...

You are quite right that its commonly used to dry alcohols, and I like your hypothesis of why its possible to do it with control. CaH₂ isn't what reacts, its the H^- that is doing the work.

Lets always remember that low alcohols that hang out on the bench can easily be 5% water, so care is definitely still needed when using it in this fashion 

@Dan and @wildfyr

CaH2 is actually very commonly used to dry alcohols like methanol and ethanol. It is one of the standard drying agents for these two solvents suggested in Perrin's Purification of Laboratory Chemicals.

C≡C-TMS can be mildly deprotected using K₂CO₃ in MeOH. It takes a couple of hours in my experience but can be usually be left overnight without detrimental effects. If the alkyne is very lipophilic and insoluble in MeOH, you can run it in 1:1 DCM/MeOH.

HF is a great reagent, but very hazardous, I would try pot carb first.

I am shocked that MeOH/KC₂O₃ works for this! But basically any fluoride source will deprotect TMS.

Either of those fluoride salts should work just fine. Do it in a mixed organic/aqueous solution like MeOH/H2O or MeCN/H2O, then do LL extraction to get your product out. Just a heads up, pick some dedicated glassware for this fluoride chemistry, it will etch your glassware a little. Won't hurt it, but it will look like crap after a couple rounds.

KFHF works well in biphasic systems with the FHF^- sitting at the interface acting with increased nucleophilicity), or F-SiMe₃^-K⁺ as the organic soluble equivalent form mixing KF with TMSF.

@Dan
That must be a typo. That would make a minor fountain

Quote from:

Try HF in acetonitrile.

For oligoribonucleotides, we used 3-TEA:HF.  It was fairly safe to work with, easily cleaned up, and gentle enough in pH to avoid damage to a sensitive molecule.

Quote

HF is a great reagent, but very hazardous, I would try pot carb first.

Definitely worth trying first to see if it works.

It does react with alcohols, but much slower than it does with water. Just brainstorming here... Maybe it has to do with the low surface reactivity of the solid CaH2, so that some of it really needs to be dissolved to react and that the alcohol solubility is very low???

What did you make of what Greene has to say about it in his essential book about protecting groups? In the 2007 version (I don't have the most recent version at hand), there are twelve sets of reaction conditions that are reported for the deprotection a TMS-acetylene.