September 23, 2019, 05:56:27 AM
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Topic: Favorite Protecting Group  (Read 210 times)

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Offline AlphaScent

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Favorite Protecting Group
« on: September 09, 2019, 11:30:47 PM »
Hey All,

What is your favorite protecting group to use for alcohols.  I have become accustom to using THP but they can fall off some times even with mild acid.  A TBS group is fairly robust but taking them off with TBAF is a pain on scale.  I always have the silane left after aqueous work up.  I usually treat with ammonium chloride and let stir for about 30 min and then extract with ether.  Wash with ammonium chloride, water, and brine.  The silane by product is always there.  Does anyone have tricks to remedy this that does not involve chromatography?  IF not, what is the protecting group you use that seems to be easy on and easy off.  PMB? MOM? THP?

Just some random thoughts from a sometimes frustrated chemist!

Cheers!
If you're not part of the solution, then you're part of the precipitate

Offline rolnor

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Re: Favorite Protecting Group
« Reply #1 on: September 10, 2019, 02:39:41 AM »
It depends completely on the conditions used in the following step in the scheme. Bensyloxymethyl can be usefull, this can be removed both with acid hydrolysis and hydrogenolysis.

Offline AlphaScent

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Re: Favorite Protecting Group
« Reply #2 on: September 10, 2019, 07:01:03 PM »
By Bensyloxymethyl do you mean like a PMB group?

So my problem is scale up.  Doing something on 1 gram is all fine and dandy.  You just run a column.  But I do not have the capability, or the desire honestly, to run a large column.  It is really expensive with all the solvent you use. 

In this particular case is would be 11-dodecyn-1-ol to protected 11-dodecyn-1-ol.  Then Sonogashira (Pyrrolidine, CuI, a vinyl bromide, Pd(Ph3)4).  Then I want to attempt a Zn/Cu reduction to give the Z diene.  Deprotection and TEMPO oxidation gives the aldehyde.

That is pretty much it.  I was also thinking if a dimethyl acetal or the glycol acetal of 11-dodecynal would survive those conditions.  I may just have to do it to see.

Anyone have experience with these types of acetals? 
If you're not part of the solution, then you're part of the precipitate

Offline rolnor

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Re: Favorite Protecting Group
« Reply #3 on: September 11, 2019, 03:55:09 AM »
No, a PMB is a p-methoxybenzyl, I mean a BOM-group.
If you are doing large-scale, can you distill att reduced pressure instead of chromatography? A silyl-group is good in this case as you suggest. Is the TEMPO really the best choise for oxidation? Swern seems more compatible with the alkene.

Offline hypervalent_iodine

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Re: Favorite Protecting Group
« Reply #4 on: September 11, 2019, 08:09:36 AM »
No, a PMB is a p-methoxybenzyl, I mean a BOM-group.
If you are doing large-scale, can you distill att reduced pressure instead of chromatography? A silyl-group is good in this case as you suggest. Is the TEMPO really the best choise for oxidation? Swern seems more compatible with the alkene.

Modified Ley Griffith would also work, I believe. For example: https://onlinelibrary.wiley.com/doi/abs/10.1002/chem.201406256

You do need to have good quality TPAP, and making it is better than buying. The stuff you order in is usually poor quality.

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