[Sach]

I wanted to couple 2 thiophenes (to reactive 2- and 5-positions) to the protected thiophene that you can find in the attachment. First I thought about doing this using Kumada coupling but I in order to perform a Kumada coupling, grignard reagents are required. I could not make Grignard reagent because they react with a carbonyl group and there is a carbonyl group present in my protected thiophene. This was the explanation I had for not using Kumada coupling (because Grignard reagent can't be made). My professor recently told me that there is another reason because of which I can't use Kumada coupling. I did some research but I really can't see another reason (Pd or Ni catalyst is used which is fine I guess).

Thank you in advance

[clarkstill]

The Kumada coupling forms a C-C bond from a grignard and a molecule containing a C-X bond (X=I,Br,Cl; normally aryl-X or alkenyl-X) - I'm not sure exactly how you hope to use it here.

[pgk]

But even being a halothiophene derivative, the amide hydrogen will immediately deactivate the Grignard reagent.

[Sach]

Thnx alot

[Sach]

Is it because the amide is acidic and will protonate the Grignard reagent?

[pgk]

Yes, Grignards are strong bases.

[Sach]

Ok, thank you very much

[rolnor]

You could try a Stille-coupling where you use a tin-derivative instead of a boronic acid. I have done this reaction and you can use PdCl2 as catalyst, I think this is because the tin-derivative reduces it in situ to Pd(0).

https://en.wikipedia.org/wiki/Stille_reaction

[rolnor]

The stannane is cheap;

https://www.sigmaaldrich.com/catalog/search?term=Tributylstannylthiophene&interface=All&N=0&mode=match%20partialmax&lang=en&region=SE&focus=product

[Sach]

Thnx
I can certainly propose this in my thesis as I have no time more left to work in the lab.

[kriggy]

You can use the halothiophene and grignard, just use more of the grignard when the first eq. will be consumed by the amidic proton.

[rolnor]

The Grignard will attack the carbamate-carbonyl?

[pgk]

Alkylmagnesium halide will give trialkylcarbinol + benzyl alcohol + (N-)alkyl 3-thiophenamide.
But usually, low yields are obtained by using excess of Grignard reagents when active (acidic) hydrogens are present; in addition to the vigorous (and dangerous) formation of hydrogen gas (windows must be open during the reaction, in order to avoid any formation of 2/1 explosive mixture).

[rolnor]

If, for example, methylmagnesiumbromide reacts with a acidic hydrogen, does this not form methane, not hydrogen?

[pgk]

Yes, but methane is not a big problem, if the fume’s ventilation is “on”.
The problem is the unreacted magnesium, which is in micro/nanosuspension form and activated by the remaining traces of the preliminary added, iodine crystal that will form magnesium hydride with the “active” hydrogen; which by its turn, will react with another “active” hydrogen and will finally lead to the formation of gaseous hydrogen.
Of course, this problem can be avoided by purchasing pre-prepared methylmagnesium bromide from suppliers.