[Reddart]

I'm following a procedure from Tet Lett 47 (2006) 4225-4229 "An improved protocol for ligandless Suzuki-Miyaura coupling in water" by D. N. Korolev and N. A. Bumagin. It is a coupling of a 3-substituted arylboronic acid and 3-iodobenzoic acid (and KOH, water, Pd(OAc)₂, under Ar).

It works pretty well, although I am getting a little of the homo coupled boronic acid product (1-3%) and a bit of the unreacted 3-iodobenzoic acid (~15-20%) with the product (before recrystallization), even with running 5% excess of the arylboronic acid (per lit. proceedure).


Besides using a greater excess of arylboronic acid (which I plan on doing, maybe at least 10% excess), could anyone suggest other changes that might help achieve a higher yield of the desired biphenylcaboxylic acid (but mainly, I want to minimize the leftover iodobenzoic acid starting material). The homocoupled sideproduct is less of a concern, though it would be nice to reduce that of course.

More dilute conditions? Higher or lower catalyst loading?  I have run them at ~0.2M with 0.1mol% Pd cat. per the proceedure. The reaction is run at RT -> 75C over a few hours.


Thanks

[Markov]

I try to go for the fastest reaction conditions I can find. In my experience, a faster Suzuki reaction tends to give higher yields and less side-reactions.

Also, 5% excess of the boronic acid is not much at all. Using 1.1-1.4 equiv might make quite some  difference.

Also, try and double the amount of catalyst and see what happens. 0.2% Pd is still pretty low.

Sometimes aqueous Suzukis are accelerated by ethanol or isopropanol as a co-solvent (10-50%). But if your partners are well soluble in H2O this might not make much difference here.

Tell us how it turns out for you.
 

[alphahydroxy]

Yeah, I would try a larger excess of the boronic acid, as Markov said - perhaps 2 eqv. assuming it is not too expensive...

I would also try using maybe 5 mol% Pd(OAc)₂, unless you are specifically trying to use minimal catalyst for your work.

If the time and materials required for a few extra reactions is not a major issue, I would try these (changing one thing at a time of course!) to get a feel for the influence of the variables, which should allow you to fully optimise the reaction and be a useful benchmark for future work.

Also, is it necessary to run the reactions under argon if you are using water as solvent? I'm not well up on aqueous Suzuki reactions - perhaps you are using de-gassed water etc?