Pd cats. for Suzuki microwave rxn.

gravenewworld

I was wondering if any pro chemists on here have a decent amount of experience doing suzuki coupling reactions. Currently I am trying to couple alkyl boronic acids to a bromo pyridine in the microwave, but seem to be having a lot of trouble. The only thing that I am observing so far is removal of the bromo, but no addition of my alkyl chain to the pyridine ring. I was wondering if anyone has any suggestions for what types of palladium catalysts/ligands/bases/temperature/or solvents I should be using for this type of reaction. I make sure before every reaction that I degas the vial with nitrogen to remove any oxygen from the solvent.

chemisttree

What kind of catalyst system are you using?
What alkyl boronate are you trying to add?

What solvent are you using? Water/THF?

Palladium acetate will work as will palladium tetrakis(triphenylphosphine). don't forget to use the alkali base...

gravenewworld

Thanks for the reply. We ended up getting around the problem by using the alkene version of the boronate ester and ended up getting around near quantitative yields for the suzuki couplings. Introducing the double bond seemed to work miracles.

we were using tetrakis/potassium carb/dioxane+water as our system.

chemisttree

I have heard that coupling alkyl groups by the Suzuki-Miyaura method needs very forcing conditions. I've seen very strong non-nucleophilic bases like t-BuOK used with halide scavengers like silver triflate (obviously no water) applied with only modest yields. Perhaps the pi system is overlapping into empty d orbital of palladium in the unsaturated versions of this reaction and the much higher energy antibonding orbitals are employed in the alkyl systems.

gravenewworld

Interesting. So far I have never had success at coupling alkyl groups via Suzuki rxns. They always have to be the alkene versions of what I want. What is great with the alkene version is that it only usually takes me 15 minutes at 155 C to get quanitative yields. Work up is a cinch too.

chemisttree

Suzuki reactions are nice that way. Have you ever thought to try making aryl silanes by this method. Current methods use grignards and is a obviously a batch process. Suzuki conditions lend themselves well to continuous processing. Have you seen anyone use Suzuki conditions to make polymers?

gravenewworld

Nah I have never seen anyone do Suzukis to make polymers, that is not the type of thing we do where I am. The only draw back that I have come across is the fact that if my molecule doesn't have any basic nitrogens I can exploit to make HCl salts of, getting rid of the triphenylphosphine oxide is a BEAR of a problem. the TPP oxide always sticks to the columns in the LCMS, makes you get terrible chromatograms when doing a silica column, and trace amounts give you terrible looking NMRs. I can remove a lot of the catalyst by dissolving the product up in DCM and filtering out the catalyst that crashes out, but it doesn't get rid of all of it. If a suzuki rxn is needed, usually I have to tailor my compound so that it will have a basic nitrogen in it.

chemisttree

You might be confusing Wittig with Grignard...

gravenewworld

_______________huh?

chemisttree

Does the small amount from the catalyst cause all of those problems?