[AlphaScent]

I am trying to form a carbon-carbon bond between a terminal acetylene/alcohol and a homopropargylic bromide.

11-undecyn-1-OTHP and 1-bromo-3-pentyne.

The procedure is to make the acetylenic grignard from ethylmagnesium bromide.  Add copper iodide and then the bromide to that at reduced temperature.

Is the copper needed?  I know the grignard can add to vinyl and aryl halides with no copper.  But this is homopropargylic , we have to worry about elimination side product.  That is why we reduce the temperature.

I have done this with copper and had about 50% conversion.  I am trying it today with no copper.  I just want to know what you think will happen?  Is copper going to be needed? My boss thinks it does not.  I think we do.  I think we will get minimal conversion.

Cheers All

[clarkstill]

I imagine the copper makes a reasonable difference; it will make the nucleophile much softer, so more nucleophilic (for the attack on a soft C-Br sigma*) and less basic.  Otherwise, I would guess that the grignard is basic enough to deprotonate at the propargylic position and give the elimination product, as you said.  What was the outcome?

[AlphaScent]

My professor was adamant that the copper would not be needed.  He was wrong.  There is maybe 1% conversion, with almost full recovery of starting material 1, the alkyne.  I believe, though cannot prove totally, that elimination is dominating.  I did it at -50 deg C.  Maybe -78 would have been better, but I am not wasting time to find out.  Copper is needed. 

[opsomath]

Does it work with stoichiometric copper only, or can you use catalytic? Not only does the copper make a softer nucleophile, it is pretty much a metal-mediated cross coupling reaction.

[AlphaScent]

100% opsmath.  It is indeed a cross coupling of sorts. When I was first looking at it I was thinking Sn2, but it is not that chemistry.  I tried 1 eq of Cu(I)I and it worked to about 35% conversion.  Also tried 0.1 eq and only was able to get around 10 % conversion.   I arbitrarily tried 0.55 and got 55% conversion.  I repeated two more times on 0.5 g and it worked.  The last reaction I did yesterday was using 0.55 eq on 9 grams and it showed 53% conversion.  So good for me.  It was a quick synthesis for the target compound.  Hydrolysis of THP; column to separate starting material, birch reduction and then Swern, I have my material.  Easy.  Just not the best yields.  All of the conversion percentages are from GC-FID print outs.

[James7364]

These reactions can be very finicky and the reactive intermediates are pretty poorly defined. I would try pre-forming the cuprate reagent if you're not already doing that.  Also what solvent?  I've found doing the reaction in Et2O instead of THF can improve many copper reactions due to the change in lewis basicity of the solvent.   Depending on how desperate you get you can also use CuCN as your copper source (note: copper cyanide is very toxic and should avoid exposure to strong acids).  CN has a very strong bond to Cu and will not be transferred and leaves the cuprate as a more reactive Cu(II) instead of Cu(I); I have had very good luck with this Cu source when others failed.

I suspect you require a full eq. of Cu because you have an alkyne present in your electrophile.  The copper will complex this part of the molecule even if you don't observe addition to it (although I would expect to see some).

Some of your conversion issues may be resulting from the CuI purity.  CuI goes bad through aerobic oxidation of the iodide to iodine which discolors the reagent to a darker brown/red. (see below on purification method).  You can also use CuBr-Me2S complex which is a more stable Cu(I) source which works great with grignard transmetallations.

Conversion can also be due to any moisture around will protonate your alkyne, and cuprates are known to add to alkynes giving the SP2 vinyl anion intermediate. So you will kill off two eq. of your grignard for every proton you have in the RXN.

You can purify CuI by dissolving CuI in boiling aq. KI, filter, and crashing out in d.i. water and washing with water, EtOH, acetone, Et2O, pentane sequentially.  Then dry it overnight on hi-vacuum while increasing the T to 100deg over 8 hrs (go too fast and you'll suck HI into your pump). Keep this in the dry box and I also wrap foil around it to prevent any iodine dissociation due to light.

Nice copper link:
http://traxanh.free.fr/Download/Modern%20Organocopper%20Chemistry/Chapter10%20Mechanisms%20of%20Copper-mediated%20Addition%20and%20Substit.pdf