[tom25138]

After a few synthetic steps I arrive at an aryl chloride, my literature method (over three papers) proceeds to lithiate then iodate my compound to end up with an aryl iodide. This Cl to I conversion has a yield 68%. By this point my working compound is neither trivial nor cheap.

The next step is a Sonogashira coupling to an ethynyl pyridine.

So here is my question, why go through the bother of changing the chlorine to an iodine (two part reaction which includes t-BuLi, working under an inert atmosphere and at -78C, when Sonogashira works with all aryl halides?

I suspect the answer is of course that iodine offers superior rates, but i can find no literature on the matter.

Thanks in advance,

Tom (i'm an inorganic chemist really!)

[MissPhosgene]

   It is possible to do Sonogashira couplings with the chloro instead of iodo. Look at J. Org. Chem. 2000,65,7110-7113. My guess is that your yields will go down.

You could look into Negishi cross-couplings as well. I think that is the best alternative to Sonogashira. Stille, Suzuki, and Kumada cross-couplings are also other options. I am not really sure what you are working with...

I am not sure if it will be any easier or better to go to a different coupling method. Try the Sonogashira on a very small scale with the chloro?

[Doc Oc]

I agree with MissPhosgene, the aryliodide is FAR more reactive than the arylchloride and that is an important component of the coupling.

Perhaps you could modify the starting material synthesis to attach the iodide instead of the chloride?  Of course, I can't say whether this is feasible without knowing exactly what you're doing to make the arylchloride.

t-BuLi halide exchanges are finicky in my experience, that could be a serious factor in your yield.  Don't necessarily trust the concentration of your t-BuLi either, especially if the bottle is somewhat old.  You can titrate it if you want to be very rigorous, but that can be somewhat time consuming (and unnecessary if you can re-design the SM synthesis).

[MissPhosgene]

Hello

Another thing you could do is modify the synthesis to get a phenol instead of a halide and then make that into a triflate. Just as good or better than an iodide....Depending on what you are doing, the phenol may be cheap.

[superg]

Hi,

the sonogashra coupling is more easy if you use an aryl iodide. reaction goes down from I>OTf>Br>>Cl. chloride compounds are quite unreactive, unless using specific palladium reagents, which are quite often expensive, no easy to make and somewhat sensitive.

usually the coupling is performed wit PdCl2(PPh3)2, becaue it's a stable solid. but you can have problem with some substrate to do the coupling with the acetylene, especially if the aryl halide substrate have some electron releasing substituants (ether, amines...). it can only work with the iodo compounds in some case.

another factor for iodo substrate is it can give better yields than the bromo one, due to the better reacticity (oxdative addition is facilitated with the iodo).

i hope this will helps

[g-bones]

Fu has looked a lot at these coupling reactions with aryl chlorides, I suggest you look at his work.  it can be efficient (more efficient than introducing an extra step in the synthesis) when bulky, monodentate, e- rich ligands are used such as PBu3.  This is a very reactive phosphine so you should only handle it in the box.  similar ligands are things like tricyclohexylphosphine, which you may be able to handle in air.  hope this helps.