[asa029]

Hi,

I'm finally done with this semester's teaching and I'm back in the lab. I'm having problems replicating some results from my last year's research. This is spesifically a Sonogashira-type coupling between a halogenated heterocycle and an alkyne. This is done with NEt₃ and THF with Pd(PPh₃)₄ and CuI as catalyst and cocatalyst respectively.

In general terms, the reaction looks like this:

Ar-X + alkyne  Ar-alkyne

The reaction (that worked in room-temperature using non-dried THF a year ago) now doesn't work at all. The only observed product is the homo-coupled alkyne. The heterocycle can be recyclled. Water and Oxygen can influence the reaction, so I repeated using dried THF under Schlenk conditions. Still only homo-coupled alkynes are observed. Anyone have any experience with this? The copper(I)iodine is a year old. Anyone think it might have oxidized?

[Dan]

Yeah, the Cu(I) may have oxidised - also, check your tetrakis Pd. If it looks like chocolate powder it's Pd(II). All you can do is check the purity of every reagent and try again. NMR ArX and the alkyne.

[Doc Oc]

check your tetrakis Pd.

This.

[nox]

I tend to stick with PdCl₂(PPh₃)₂ for Sonogashira couplings. Works just as well and don't have to worry about stability since it's a Pd(II) pre-catalyst. I've used this and successfully coupled both thiophenes and pyridines.

[asa029]

If it looks like chocolate powder it's Pd(II)

The tetrakis palladium was recently bought from Sigma (the one I had used last year seemed to completely have oxidized over a year and was not used for the reaction). The new tetrakis palladium was clearly crystalline orange/yellow and seemed okay. The problems probably didn't stem from the palladium.

[Honclbrif]

If the only product you're getting is the homocoupled alkyne, it sounds like your copper is the issue.

[g-bones]

if homocoupling is a significant problem, it sounds like oxygen is an issue.  The THF you used, you said you dried it, but is either gas free or sparged with N2 or argon? I also agree that its worth checking out your CuI.  If you have easier access to dry and oxygen free triethylamine, you can try just running it in that.  Just to be extra safe, I typically sparge my reaction mixture for about 15 minutes with N2.  Give that a shot too. 

[nox]

I run all my Sonogashiras in triethylamine. I just use the ">99.5% redistilled" Sigma stuff straight from the bottle. Never bothered with any degassing and I usually get >80% yields. Homocoupling was never an issue for me either.

[Sepelio]

Check the triethylamine. Someone in our lab was doing coupling reactions that wouldn't work. They found out the triethylamine was poisoned with methanol and was ruining the reactions.

[cpncoop]

Degassing is usually the issue when catalyst issues have been ruled out, especially if it worked previously.  I'd sonicate your reaction mixture under a slight vacuum for 30 min prior to catalyst introduction (under schlenk conidtions at that point).

[bunky]

It's most likely an oxygen issue (Grubbs columns do not remove oxygen).  I'd also be careful about the amount of copper that you are using.

I hate THF for Sonogashira conditions; my standard conditions are 30% diisopropylamine in toluene. I make a big batch once a year and store it in an Airfree solvent bomb and using reasonable practices, lasts about that long.  As far as catalyst loads, I use 5% tetrakis and 3% copper(I).  Room temp for iodides and 40-60C for bromides, works every time guaranteed.

[opsomath]

I second the people suggesting toluene as a solvent. I always used Pd(II), not Pd(0), CuI (it should be grey or colorless) and did it under nitrogen with heat in toluene. I sparged with nitrogen for a bit before adding the reagents, just to be sure oxygen was gone. I used Hunig's base or TEA, never noticed a difference between them, but I distilled them from sodium before use. Homocoupling is definitely an oxygen issue, either that or you are using way too much copper and it has copper (II) in it.