[GSK]

No matter how much degassing I do, I always get huge amounts of alkyne dimer whenever I do a Sonogashira. My conditions are: dienyl iodide in benzene, add tetrakis-triphenylphoshpine palladium, then 45 min later add BuNH2, followed by CuI, flush well with nitrogen, then slowly add alkyne. With newly opened, high-purity reagents, I still get at least 40-50% dimer. Everytime. What am I doing wrong?

[Ψ×Ψ]

What's the alkyne?

[GSK]

it's a short chain propargyl alcohol (hydroxyl protected as silyl ether), terminating in an ester or amide

[Mitch]

Prepping the catalyst is all the rage these days. It usually involves allowing the CuI and Pd catalyst to mix with the halide for 20 minutes before you do the slow addition of alkyne. Also, are you using a syringe pump to really make sure your doing a slow addition.

Also remember, I believe the amount of material lost to dimer is 2:1 ratio of the amount of Pd you add. So, if your using 50 mole percent of catalyst, you just chewed up 100 mole percent of your alkyne. Actually, I thought sonogashiras typically use Pd(II)bistriphenylphosphinedichloride. This paragraph might be more relevant for the dichloride prep actually...

[Ψ×Ψ]

Mitch: There's no super-specific requirement for the catalyst.  I ran one just yesterday using tetrakis.
Usually it's a degassing issue, AFAIK.  Perhaps the reaction faeries just have it in for you.

[GSK]

I use 5% [PPh3]4Pd and 10% CuI. Never get a yield above 60% with no unreacted alkyne-it either forms product or dimer. I will try more rigorous degassing this week and report back on the results. thanks

[wintermute]

did you go through orgsyn.org? there is load of sonogashira couplings.

[GSK]

By TLC it appeared that I had very minimal dimerization, but my yield was only about 64%, with no starting materials recovered. I will repeat it with the same level of degassing (handling of Pd catalyst in glove box, anhydrous, degassed solvents, protected from light, etc)

[PRIYA1022]

 I have done a bunch of Sonagashira couplings with TMSA and aromatic Iodides.I used Pd(II) bistriphenylphosphinedichloride(1% to 10%)and CuI(10%),and triethylamine.However for one compound,(methyl-2-iodo-3-nitrobenzoate) my yields were bad, and I had the dimer of the alkyne and the starting material.How many equivalents of the alkyne did you use?and is there a lit.ref for your reaction?
Do you mind giving the chemical equation for your reaction?

[GSK]

I dont have the lit references right now (Nicolaou has published some similar couplings), but it's an alkyl diene iodide (1 equiv) + a propargyl alkyne (1.5 equiv), n-BuNH2, [Ph3P]4Pd (5% mol), CuI (10% mol) in benzene. I'm getting acceptable yields now (65% is about typical) but the dimerization of alkyne is a signigicant loss because I have a series of derivatized alkynes that are not simple to make, so I don't want to waste them to non-productive side reactions.