[phth]

Why not use/make boc bromoaniline (moderately priced or easy to make) and do a test reaction? I bet it is somewhere in the literature though.

+1

Cbz should go off.  The thiophene α position is extremely easy to modify, and there are multiple ways reported in the literature.

[wildfyr]

I expect I can find the answer in the literature in less than an hour, this a fairly obvious protecting group to have to deal with. I really think you should check again yourself  before wasting money,  time and energy, albeit on an easy test reaxtion. I will look tomorrow when I can use a PC, but if it's easy to find I may shame you

[wildfyr]

I spent some time searching, and I could not find an example of a direct arylation using Pd(0) in the presence of a tBoc group. However I found many examples using Pd(OAc)₂ such as http://pubs.acs.org/doi/abs/10.1021/ja058141u, http://pubs.acs.org/doi/abs/10.1021/ja0605265 or http://pubs.rsc.org/en/content/articlelanding/2013/sc/c3sc50428j#!divAbstract. So, in light of that, my suggestion is to put another few hours into scifinder/google scholar seeing if you can find an answer, and if not, give the test reaction a shot.

P.S. A subtlety, all the examples I found with palladium acetate had boc protected alkyl amines, for whatever that is worth.

[Sach]

I did find an example where SO2-ph is used as protecting group (see scheme 184 p214) using the same conditions while performing direct arylation reaction:
http://pubs.acs.org/doi/abs/10.1021/cr0509760

p-toluenesulfonyl chloride is is sometimes used as protecting group but this is the first time I have seen benzenesulfonyl chloride (SO2-ph) as protecting group. Is it possible that any one of those two could be used as protecting group?

[Sach]

And thnx a lot for the help.
I have actually finished my research in the lab, now I have to look for possible reasons for obtained results while writing my thesis. So I won't be able to actually work with the protecting group I chose, but i still need to give an alternative protecting group (for people who would want to do similar research in the future).

[rolnor]

It could work, I think you remove it with Na/NH3? I think I have seen that, att least for the tosylgroup, the benzenesulphonylgroup should should be similar. Its i pity you have no more time in the lab, this is interesting chemistry.

[Sach]

Yes I wanted more time as well but it was a relatively short project. So I am going to propose P-toluenesulfonyl chloride as alternative protecting group instead of benzyl carbamate. It is reasonable to propose this, right?

[rolnor]

Maybe there could happen something with the thiophene-ring if you deprotect with Na/NH3 and the DA can be slower because the Tos-NH- is less activating then Cbz-NH- but the tosylgroup is more stable to basic and acidic conditions.

[wildfyr]

You can probably n hydrolyze tosyl with aqueous KOH. I don't know at all how thiophene would handle that

[rolnor]

The thiophene is aromatic and will not react with acid or base but the method using Na/liquidNH3 to remove tosylgroups is more of electron transfer or free radical type of reaction so the sulfur in the thiophene-ring can somehow react perhaps. If it is OK to not de-protect after DA this is of course no problem.

[rolnor]

I found this link, they use Li and naphtalene to cleave tosylamides, I think this is similar to Na/NH3.
http://www.organic-chemistry.org/protectivegroups/amino/toluenesulfonamides.htm

[Sach]

I also saw that it is cleaved by  Li and naphtalene. Can it be cleaved with using KOH like wildfyr said? Because thiophene can certainly withstand KOH.
If the organic linker is succesfully designed, a metal organic framework will be synthesized with it. The target is to deprotect it after the direct arylation but if that is not possible, the alternative is to deprotect is after the metal organic framework has been synthsized but that would be more difficult i imagine.

[kriggy]

You could use nosyl instead of tosyl and cleave it using thiol (mercaptoethanol or thiophenol AFAIK) at mild conditions. It smells but might be better than refluxing it with KOH or H2SO4

[Sach]

Ok thnx