[willug]

Hello all.

I'm currently trying to do a sonogashira coupling -so it should be easy! - but the problem is I have an azide elsewhere in my molecule which seems to be getting reduced (Staudinger type reduction with the phosphines I guess) under the reaction conditions (I do get some, ca. 15%, non-reduced product out). But ideally for the synthesis that should not happen!

I guess the answer is a ligand/phosphine free catalyst, but I was curious if anyone else had had this sort of problem or come across any papers describing any solutions? I've found (surprisingly?) little searching SciFinder unfortunatley...

[Dan]

What conditions are you using? Do you see any click chemistry (if you're using Cu)? Have you tried a Cu-free variant?

[willug]

I actually hadn't thought of that, so thanks for pointing it out. I did start with just Pd(PPh3)4, CuI and DIPEA, but didn't see any click products... Just my product with the azide intact, amine (I think), and homocoupled alkyne.

Tried a couple of copper and ligand-free variants (Pd/C, PdEncat) but haven't been able to get anything to go yet (starting materials recovered).

I'm starting to think doing the coupling earlier in the synthesis might be the answer now 

[opsomath]

Please keep in mind that cross-coupling reactions can happen with azide as a coupling partner (pseudohalogen) if it is aromatic or unsaturated.