[AlphaScent]

So I was thinking today about the synthesis of 1-hexyn-3-ol.  What comes to mind is the reaction of ethynylmagnesium bromide and butyraldehyde (butanal).  I have used ethynylmagnesium bromide before and it is a fickle compound that only comes from suppliers as a 0.5 M solution.  It is also prone to disproportionate.  It is just no fun.  Making it I am told is also a task.  You would add the aldehyde to the  grignard to lower your chances of side reactions (aldol). 

What about the oxidation of propargyl alcohol to the corresponding aldehyde?  Swern can be done on a large scale.  Then an addition of n-propyl lithium at cold temperatures in theory could work.

But, there are issues to be resolved:

Would the acid/base reaction of the acetylenic proton and the n-propyl lithium predominate?

Could that acid/base reaction be mediated by 2 equivalents?

Would the side reaction predominate of the acetylide and aldehyde be too much in competition with wanted product?

Also, why is n-propyl lithium not as predominant as n-butyl lithium?  Is one more carbon that much more stable?

Answer part or whole or none of this, thanks for any input!!!

Cheers!

[AlphaScent]

I think this could work with a silyl group at the acetylenic proton.

[zsinger]

I second Alpha.  Be very careful on those acetylene protons, as they are notably easy to snag off there with a medium-strong base.

[Archer]

Also, why is n-propyl lithium not as predominant as n-butyl lithium?  Is one more carbon that much more stable?

Answer part or whole or none of this, thanks for any input!!!

It's weird, methyllithium, ethyllithium, butyllithium and pentyllithium are all commercially available in various solvents from Aldrich, but no propyllithium.

Maybe it's a stability issue or maybe the reactivity is such thst you get an unpredictable and non reproduceable mixture of base and nucleophillic competition.

Just a guess I'm afraid!

[KeV_In]

This is a "classic" synthetic problem to test one's understanding of C_sp-H acidity, and protecting groups. Hint: what is the pK_A of C≡C-H bond compared to an aliphatic CH bond (as in n-butane).

As for propyl lithium, it helps to know how butyl lithium is made, and the availability/hazards of the feedstocks. If the Li⁰ route is used, the volatility & toxicity of 1-bromopropane makes it more dangerous than 1-bromobutane

[Archer]

As for propyl lithium, it helps to know how butyl lithium is made, and the availability/hazards of the feedstocks. If the Li⁰ route is used, the volatility & toxicity of 1-bromopropane makes it more dangerous than 1-bromobutane

That doesn't explain the commercial availability of methyllithium and ethyllithium.

[AlphaScent]

Kev_in

I understand your point.  But bromopropane is no more dangerous to work with than bromobutane in my opioion.  Though there very well be something I am overlooking.  I understand the nature of protecting groups and have come to the conclusion you would have to protect the proton. I appreciate your response.

You too archer, I think it is all conjecture.  Maybe ill just call and ask ha!

Sorry for the delay; I was in Florida fishing!

Cheers All