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I've done a very similar reaction to the one below but by TLC I observe only starting materials. It's super clear that nothing else is going on. Conditions: K3PO4, Pd(dppf)Cl2, dioxane/water, heat to 100 deg.C.

enter image description here

What thoughts do you have on why this doesn't work?

  1. I imagine the alkyne chelating to the Pd and potentially 'poisoning' it? I currently lack the words and technical lingo to put this into a formal explanation.

  2. A competing Sonogashira perhaps? Unlikely given the aqueous conditions.

  3. Any other issues?

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  • $\begingroup$ I don't see the alkyne interacting with the Pd being an issue. Any competing Sonogashira will be dependent on your choice of catalyst, base and solvent. $\endgroup$ – Waylander Apr 28 '17 at 9:28
  • $\begingroup$ @Waylander Assume fairly ordinary conditions: dioxane/water, K3PO4 as a base and a slight excess of the boronic acid. Heat to 100 deg. C. I've actually done a similar reaction and did not see any coupling product. By TLC it was literally just starting material. What would you propose as the issue? $\endgroup$ – Hazinga Apr 28 '17 at 11:11
  • $\begingroup$ @Waylander I've updated the reaction to more closely align with what I did. I can't show the exact structure for confidentiality reasons. NOTE: I have carried this out in the lab to no avail. $\endgroup$ – Hazinga Apr 28 '17 at 12:36
  • $\begingroup$ What catalyst did you use? $\endgroup$ – Waylander Apr 28 '17 at 14:01
  • $\begingroup$ Try Fu's standard 'wet' Suzuki conditions of tricyclohexyl phosphine, Pd(dba)2Cl2, K3PO4, in dioxane/water as described in Tet. Letts (2001) 4295 $\endgroup$ – Waylander Apr 28 '17 at 14:15
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If TLC is the only analysis we have, it may be difficult to determine exactly what is happening (or not happening). Other things that might be happening include homocoupling (biaryl formation), proteo-deborylation, and debromination. These may be hard to discern by TLC alone.

If there is no reaction of starting materials this might be due to:

  • Failure to reduce Pd(II) precatalyst to active Pd(0) species: your catalytic cycle never initiates. Consult chapter 1 of Negishi's Handbook of Organopalladium Chemistry for Organic Synthesis. Consider adding a catalytic amount of exogenous reducing agent, changing the solvent to EtOH/PhMe/H2O, increasing the temperature, switching to a Pd(0) catalyst system, or a system that is more easily reduced to Pd(0) like Pd(OAc)2 + xs phosphine ligand.
  • Stalling in the catalytic cycle: there is insufficient energy to get over the activation barrier in the oxidative addition, transmetallation, or reductive elimination step. Try increasing the temperature.
  • Catalyst destruction by oxidation: did you degas your system with N2 or Ar?

Alkyne poisoning of the homogeneous Pd catalyst seems unlikely since there are plenty of examples with Sonogashira coupling of terminal alkynes involving dppfPdCl2 that work just fine.

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