[dainnius]

Hi,

Could you please give some tips how to couple these 3 babies into one terthiophene (see picture below)? I have performed so many reactions, but it does not work properly (Pd[0] catalyst, various solvents, Cu(I) additives and CzF additives)..the yields are ridiculous and the purification is a one real bloody hell!!!

Thank you for your help....hope someone knows how to couple these electron-rich, sterically hindered bastards...

Waiting for your answers...please free me from this hell....

[OC pro]

Have you tried Suzuki coupling instead? This worked really well for us on a 2-bromothiophene. Moreover, we also did a pinacol boronate from a 2-bromothiophene. This will work. For making aryl-aryl couplings, Suzuki coupling is the method of choice.

[dainnius]

I tried suzuki. Made a pinacol boronate and then used toluene/Na2CO3 aq as a base and Pd0 as a catalyst. did not work (no reaction at all!). then tried in DMF with the same  base and catalyst...no reaction....grignard and kumada failed also (since it is too hindered)...

could you please give me a procedure of that coupling? please note, that the tings I want to couple are very very stericaly hindered and very electron rich and I need to perform a double coupling.... guess it is my bad luck

anyway, thanks for your answer.

[OC pro]

I will look for it tomorrow in our in-house database. What are the R´s? I hope not something like isopropyl or tert butyl? Your result from Suzuki doesn´t sound too bad. At least you have no decomposition. I think you can give a second try on this one. With a more reactive catalyst or a higher catalyst loading you should at least get some material. There should be some special procedure in the literature for Suzuki couplings with sterically hindered aryl bromides. I assume a yield of 30% is the maximum what you can achieve in this reaction.

[nox]

Above posters pretty much said what I would've said. Though I guess if you can afford it, try to make the iodo analog and see if that works better. Also maybe try the boronic acid instead of the pinacol ester and see if that does any good.

Also maybe try using P(tBu)3 as a ligand in your reactions. I've gotten a couple of tricky Sonogashiras to work (very electron-rich/hindered aryl bromides) which otherwise failed if I didn't have P(tBu)3 in there.