[AlphaScent]

Does anyone have any literature or experience in monoprotecting diols to yield the THP/alcohol?  Google is not helping much and I do not have access to reaxys ect.

I understand it would be 0.5 eq of DHP to the diol.  But is there anything else to take into consideration?

Thank you in advance, stay cool.

[discodermolide]

Why do you need the THP ether?
Could you get away with something else?

[Archer]

I have published data for extremely good selectivity on using an excess of dihydropyran with pyridinium toluenesulphonate on a diol. It is very substrate dependent, could you give more details about your compound?

[AlphaScent]

Hey guys,

I cannot get away with anything else.  THP ethers are the norm around here.  They are cheap and labile. 

The compound in question is 1,10-decanediol.  I am trying to protect one end and then use swern oxidation to the aldehyde and react the generated aldehyde with vinylmagnesium chloride.  I have looked into other ways of making this and was first trying a grignard on acrolein, but acrolein is hard to come by for some reason.

If you have published on the monoprotection of diols, could you forward me an excerpt if it applies to my chemistry?  Be a big help to have as a reference.

Thanks again!

Cheers!

[Archer]

If you have published on the monoprotection of diols, could you forward me an excerpt if it applies to my chemistry?  Be a big help to have as a reference.

I'm afraid that it doesn't apply here as the two hydroxyls in my molecule were not equivalent.

I also should have checked the paper before I posted this as I didn't use pPTS I used triphenylphosphine hydrobromide as the catalyst.

This is not my paper but this is the method I used http://www.sciencedirect.com/science/article/pii/S0040403900805535
This may help.

The problem with trying to react just one of two equivalent functional groups is that as the reaction proceeds the concentration of mono-THP substance increases so it is more likely to react with the dihydropyran than the diol which is in low concentration.

You will end up with a mixture of mono, di and non protected diol. Having said that as your starting material is relatively cheap and the mono-THP should be the major product (how major I am not sure) you could afford to separate them by chromatography or short path distillation if you have a decent vacuum pump.

[orgopete]

This looks like a shut your eyes and try it. If totally selective, 100% yield (I doubt it). If totally unselective, then a 1:2:1 mixture. If the mono reacts faster, then only di-protected and diol as product. In that case, I'd try oxidation, then protection. If lucky, it would form hemiacetal, skip protection and use two equivalents of vinyl lithium, or just skip protection and use two eq of vinyl lithium.

[opsomath]

I bought acrolein from Alfa Aesar quite cheaply in grad school.

Honestly, your best bet here is to add your DHP slowly into a solution of excess diol, then find a chromatographic separation on which the diol starting material doesn't move at all. You'll need to iodine stain to visualize TLC.

I'd seriously consider an alternate route, though.

[orgopete]

I'd seriously consider an alternate route, though.

If I had the diol in hand, I'd try oxidation with one equivalent, fish out the aldehyde-alcohol, and add two equivalents of your vinyllithium. I'm guessing even with unoptimized yields, you'll have more product, though you will waste some vinyllithium.

[opsomath]

What's the starting material you were going to use with your Grignard/acrolein route? Do you have that on hand?

[AlphaScent]

Soooo i tried this...

I used a large excess of the diol, 0.25 eq of DHP to the diol.  I also had to use THF because the diol would not go into DCM.  Diol was dissolved in warmed THF and added to that was 0.25 eq of DHP followed by a few crystals of PTSA.  A condenser was added (because it is 95 in syracuse and our AC broke) and it is stirred overnight. 

Running TLC the next morning shows a small amount of a new compound.  I rotovaped off the THF and am trying to rinse the solids with hexane to see if the THP ether will go up in hexanes.  That is where I am at. 

Why use iodine stain?  phosphomolybdenic acid works good for what I do.  no problems with it.

[AlphaScent]

The starting material was 1,9-nonanediol.  Treating that with HBr in toluene using a DST resulted in the bromohydrin.  The bromohydrin was then protected, which actually resulted in a mess.  Distilling that THP bromide is tricky and easily can degrade under high temp, even under vacuum.  I was going to make a grignard out of said bromide and react it with acrolein.  But acrolein from any common commercial company is not happening at this time.  Back ordered indefinitely.

[opsomath]

Oh, the Mo stain is a good one. We didn't have that around in my old lab where I did this kind of annoying stuff

It just occurred to me, though, that if you are hoping to do Swern on the next step, it has an inherent problem. Swern makes HCl as a byproduct, like many oxidations.

[opsomath]

What's a DST?

[AlphaScent]

I brought up the same question resulting from swern.  PCC is inherently acidic and my company isnt going to spend for dess-martin or anything.  I think swern should work ok, we will see though.  I will post about my results.

A DST is a Dean-Stark trap used to remove water from the equilibrium to push the reaction to completion.  In using it with toluene it works by removing the water due to the azeotrope formed between water and toluene.

[opsomath]

Oh lol a Dean-Stark trap. Acronym identification fail.