[polyrene]

Hi guys...

There is a question for u. I have a problem in choosing catalysts for stille coupling of thiophene with Boc-N-pyrrole. Which one is best to do: tin compound of pyrrole or of thiophene? which catalyst is better to use Pd(0) or Pd(II)?

Actually there is a confusion with these catalysts. Why in all papers it is written that Pd(0) is usually used with toluene and boiling temperature. And Pd(II) is used in THF and milder temperatures? What if I use Pd(0) in THF? or Pd(0) in toluene but will not boil it (my compound might be unstable).? does anyone have such experience?  which catalysts are more sensitive to oxygen? PD(0) or Pd(II)? I guess Pd(0)? I know the mechanism of stille. Reactive specie is Pd(0)...but still why people then use Pd(II)?

thanx

[polyrene]

oh come on! don't say that no one ever done Stille of pyrrole and thiophene!

[sjb]

oh come on! don't say that no one ever done Stille of pyrrole and thiophene!

Well excuse me for working today. Someone's got to pay the bills you know!

Which positions are you looking at coupling? Is there any similar precedent in the literature? In my experience it's slightly better to have an stannyl thiophene, but very little in it, and I don't have a great deal of examples. Pd(0) is more oxygen sensitive, again in my experience, which is why Pd(II) is sometimes used (it then gets reduced in situ)

How precious are your coupling partners? Why not try Pd(0)/THF and see what happens?

[Arctic-Nation]

Ah, patience.

As sjb pointed out, our help would be better if we knew what positions we were looking at. Stannyl thiophene is probably easier to prepare/buy than stannyl pyrrole. As for the catalyst, trying a few different ones or different conditions is your best bet. Start with Pd(PPh₃)₄ or PdCl₂(PPh₃)₂, keep your reaction dry and free of oxygen and you'll be set.

I've done Stille reactions with Pd(0) in THF without problems, though in the procedure I followed CsF (about 2 equivalents) was also added to the reaction mixture. You'll just have to try and see.

[polyrene]

thanx  probably i will try THF with Pd(0)....thou I would not like to put anything else ther (like CsF)...we will see.

[kiwi]

Both Pd2dba3/Ph3As or Pd2dba3/P(furyl)3 are very active catalyst systems. Both are much better than Ph3P based catalysts, there is a paper out there with a comparison. You probably do want to be adding other things too - eg. both LiCl and CuI can give big improvements.

[polyrene]

could you please send a link to the paper? I am a bit lost: before I was using Cu(II)Oxide (according to experience of my group members)...when I have stopped using it - yields did not improve or decreased.

Thank you,

Poly

[kiwi]

CuI: J. Org. Chem., 1994, 59 (20), pp 5905–5911

Ph3As/P(furyl)3: J. Am. Chem. Soc., 1991, 113 (25), pp 9585–9595

Those should get you started

[polyrene]

but according to this paper....if I have Pd(0) I do not need any additives! It is already active and can participate in reaction.

"This predissociation event is thermodynamically unfavorable for “strong”
ligands such as PPh3, and in this case slow destruction
of the ligand (by air oxidation) is necessary to induce
coupling.2b Another strategy to diminish the concentration
of PPh3 in solution is apparently to allow its
complexation with a second metal, in this case Cu(1)"

So, how it is? That is the main issue. There are a lot of Pd catalysts. But we are using Pd(0). Because of the theory: Pd(II) in the reaction first goes to Pd(0) and then reacts. additives helps in this stage. But we are using already active Pd(0)...so why then put anything else in it? Am I wrong? Also, what can you say about solvents for these reactions? Have you ever seen any paper when Pd(0) is used with THF? Why nobody did this? Is there a reason?

Thank you

[kiwi]

Not entirely sure what you are getting at. You still need ligands for the Pd, what the paper is getting at (without reading it) is the position of this equilibrium:

Pd(PR3)4 (inactive) -> Pd(PR3)2 (active)

Displacing this equilibrium toward the right (and the active Pd species) is comparatively hard for PPh3, but easier for electron-poor ligands like Ph3As and P(furyl)3