[AlphaScent]

Hey all,

I have just tried to couple a tosylate, 3-pentyn-1-oTs and a THP protected terminal alkyne/alcohol.  10-undecyn-1-oTHP.  I used butyl lithium at -78 to rip the proton off the terminal alkyne.  Then added the tosylate in HMPA dropwise.  NMR shows minimal product and seems as though elimination predominated to the ene/yne product for the 3-pentyn-1-oTs. 

This in theory seemed to be a good reaction, but in practice was not. 

What do you all think I can do differently?

My ideas are:

Make the bromide instead of the tosylate?

Make the grignard from ethylmagnesium bromide instead of using butyl lithium?

Does anyone have any experience with this?

Thanks for your thoughts

Cheers!

[discodermolide]

Why not try inverse addition, add the base to the tosylate.

[AlphaScent]

Thats an idea for sure.  I think I may try making a grignard.  A colleague of mine gave me a procedure that he did in a similar reaction and got 60% yield.  Not too bad, but not great.  I think on a small scale disco I am going to try an inverse addition though to test that theory.

[orgopete]

I agree that an ene-yne product might compete in this reaction. Conventional wisdom is that elimination is the primary product with an acetylide and a secondary halide. This is how I rationalize this occurring. In an SN2 reaction, I think of it as though the nucleophile must hit the carbon to force the loss of the halide, like a que ball striking two balls to drive the ball not struck by it. Protons enable attack and electron donors interfere with it. If elimination is occurring, then I think the C-X bond is being stretched and neighboring electron are competing for this backside attack. If that is the case, the pKa of the hydrogens decreases and it's electrons are interfering, both of which enable an elimination.

I think the triple bond does the same thing, though in a paradoxical way.  Triple bonds are more electron withdrawing and are subject to isomerization. I think of this as due to the triple bond pulling electrons towards it and thus increasing the acidity of the alpha protons. However, in this case there would be two groups attracting the electrons of this bond. The net result would be an increased acidity and enable elimination.

I agree with trying a Grignard as magnesium is a better Lewis acid and may reduce the competing deprotonation. The other way would be to use a metal to do the coupling. I'm guessing other forum contributors will have greater practical knowledge than I and can probably make a good suggestion. I think this will prove to be the more successful strategy.