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Author Topic: Acetylide Formation  (Read 441 times)

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AlphaScent

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Acetylide Formation
« on: February 08, 2017, 12:10:00 PM »

Any tips on forming the acetylide of 3-butyn-1-OTHP?  It will then be reacted with (4Z,7Z)-1-bromodecadiene in an SN2 type fashion.   I tried lithium amide in THF (3 ml/mmol) at 0 degrees C with the bromide being added in HMPA at 0.25 ml/mmol. There was no reaction.  I suspect a solubility issue with lithium amide.  I want to try the reaction in liquid ammonia and then maybe DMF.  What do you all think? 

It should be noted that the reaction worked marginally (40% conversion by GC) when n-butyl lithium in hexanes was used as the base in THF at -78 then up to -30 then back to -78 for bromide addition.  Side products resulted.
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rolnor

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Re: Acetylide Formation
« Reply #1 on: February 08, 2017, 01:18:31 PM »

I feel that the 40% conversion with BuLi in THF is a good start. Do you use HMPA in that case also?
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AlphaScent

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Re: Acetylide Formation
« Reply #2 on: February 09, 2017, 05:27:48 AM »

rolnor,

Yes. HMPA is used. 

The issue is the THP comes off when the nBuLi is used.  The other issue is I was given 900 g of the 3-butyn-1-OTHP; I am not making that into TBS or anything.  I have done many alkylations in liquid ammonia.  Tomorrow I will do the following:

Lithium Amide (from Aldrich, I should make it fresh though) will be placed in flask and then liquid ammonia collected.  Dropwise addition of acetylene in anydrous THF.  Let stir for 45 min.  Add bromide drop wise with minimal dry THF.  Let stir for 3 hours.  Add some dry ether and let the ammonia evaporate over night.

Ill let y'all know.

Cheers
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orgopete

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Re: Acetylide Formation
« Reply #3 on: February 09, 2017, 08:07:19 AM »

I don't think basicity is the issue. I think allene and elimination are likely and consistent with the loss of the THP.
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rolnor

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Re: Acetylide Formation
« Reply #4 on: February 09, 2017, 09:02:04 AM »

Maby LDA in HMPA att low temperature? I would use a fresh bottle of LDA or make it myself from fresh BuLi and diisopropylamine.
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AlphaScent

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Re: Acetylide Formation
« Reply #5 on: February 09, 2017, 11:07:36 AM »

I do not think basicity is an issue either.  If it gets too warm I think elimination is certainly a possibility.  I think the solubility of lithium amide in THF was a big issue.  No acetylide formation.

I recovered Both SM
 
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química brasileira

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Re: Acetylide Formation
« Reply #6 on: February 10, 2017, 07:43:36 AM »

Hello my friend,

i think your trying to remove a acetylide proton right? instead of lithium bases i would suggest that you use TMP MgCl-LiCl (2,2,6,6-Tetramethylpiperidinylmagnesium chloride lithium chloride complex solution) http://www.sigmaaldrich.com/catalog/product/aldrich/703540?lang=pt&region=BR, or even use a commun gringard generated BuMgBr, and then add your alkynyl compound, this way u will generate the acetilide MgBr and most likely will have the addition.

i can provide the proceaddure, its quite easy and u can do it at r.t.

PS: sonogashira coupling is ALWAYS a solution. u wont need to protect with THP.
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AlphaScent

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Re: Acetylide Formation
« Reply #7 on: February 13, 2017, 11:26:31 AM »

Hey All,

The reaction worked great under the conditions I gave!!  Thanks for all the help.  The issue is still that it worked well with 10% mole excess THP protected alcohol.  Have to do the next two steps (deprotection, dissolved metal reduction) and then will distill.  Thanks again for all the help.

Quimica,

The story here is that I am doing some contract work for my old job and somebody took a teacahing gig half way through a synthesis of 300 g of a material.  I already had the THP ether and need to just go forward with it.  But....DO NOT GET ME STARTED on palladium cross couplings.  I have been for years trying to get my bosses to do this type of chemistry as opposed to "old school" SN2 type reactions that may or may not work.....trust me I know that it is ALWAYS a solution.....especially nowadays.

Kind Regards
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