[Sach]

I am currently working on a project of organic chemistry (like some of you already know). I got the task to make a large molecule by coupling thiophenes. Molecule 1, the protected aminothiophene,(in the attachment) is what I start with. In the attachment you can also find the proposal I have (making 2-bromo thiophene, followed my preparation of a grignard reagens and then coupling the thiophenes to each other).
Any remarks, advice or other proposals are more than welcome.

[wildfyr]

Can't make a grignard in the presence of that carbamate. Pathway is no good.

[rolnor]

You could substitute  the 2,5-dibromothiophene with thiophene-2,5- di-boronic acid and use the 2-bromo-3-Cbz-amino-thiophene as is using Pd(0) catalysis. I dont know if you can buy thiophene-2,5-di-boronic acid.

[wildfyr]

Rolnor, you're better than that

http://www.sigmaaldrich.com/catalog/product/aldrich/470317?lang=en&region=US

first thing that popped up for googling "thiophene-2,5-di-boronic acid." It can also be made without too much trouble I bet (scifinder away).

[Sach]

Thank you for the quick reply guys.
Rolnor, do you mean the reaction I attached in the attachment?
Wildfyr, why is the making of a grignard not possible in presence of that carbamate?

[wildfyr]

Grignards react with carbonyls. A carbamate has a carbonyl.

And to fill in for Rolnor, you are missing a bromine at the 1 position on your thiophene-2-carbamate to do the proposed Suzuki coupling.

[Sach]

Ooh ok, thank you.
Do you have a proposal by which I can couple thiophene to thiophene-2-carbamate?

[wildfyr]

... rolnor just proposed a method. Suzuki coupling.

[Sach]

Ooh ok but I don't understand why the reaction I proposed isn't correct?
I actually didn't understood your comment 'you are missing a bromine at the 1 position on your thiophene-2-carbamate to do the proposed Suzuki coupling.'
Thank you for your understanding.

[wildfyr]

Well what two partners do the coupling in a Suzuki coupling? Do you have those in the scheme you drew just now?

[Sach]

Ooh yeah I get it. The thiophene carbamate needs a bromine.

[rolnor]

Yes, thats what I suggest. One problem could be steric hindrance from the Cbz-aminogroup, the reaction can be slow or you need to heat.

[Sach]

Ok, I will search for a complete procedure for bromination first.
And for suzuki reaction, would I need an excess of thiophene-carbamate or would 1eq of both be sufficient?

[rolnor]

If you want the desired product you need 2 eq. of the thiophene-carbamate, not?

[Sach]

Ooh yeah you are right.
I also have a question about bromination of thiophene carbamate. I have seen in some articles that thiophenes are brominated using NBS and using THF (of glacial acidic acid) as solvent. I don't know the mechanism by which this reaction takes place so I don't know if thiophene-carbamate can be brominated like I propose in the attachment.