[Grimer]

Hi!

I've just started to dig in to the subject of Transmetalcatalyzed C-H activation in Organotransiation metal chemistry by John Hartwig, and I'm confused about two things:

Is the spot where the C-H-cleavage takes place favoured if it's more of a positive charge character/delta plus unlike uncatalyzed C-H-cleavage where minus is favoured, or is it more complex than that?

(p. 832-835) On directing groups such as functional groups or heteroaromatic systems that bind to the metal, it is written that the directing groups "allow for regioselective functionalization of a C-H by directing the chemistry to the position ortho to the ligating substituent".
They present this example which confuses me a bit:
http://imgur.com/5yne2hh
Since it is ortho to the hetereoaromatic system and not to the methoxy, does this mean it binds stronger to the former than the latter? When it comes to directing the reaction on benzenes, does it have more to do with the binding between the metal and directing group than the electronic effects the directing group has on the ring?

Would be much appreciated if someone could shine just a little bit of light on any of these problems Thanks!

[phth]

references?

[Grimer]

references?

I've tried to check with the reference given in the book, but I can't get a hold of the original litterarute

[k1mng]

DOI: 10.1021/ol060747f

To clarify, the ortho-directed halogenation in the Pd-catalysed scenario is favoured probably due to chelation of the Pd metal centre during its catalytic cycle if it were to insert into the C-H bond. I would think also that nitrogen atoms tend to be better electron donors than oxygen (this is to do with the higher electronegativity of the latter), although it being a heteroatom in an aromatic ring - as with pyridines - may attenuate its ability to act as an e donor.

The ortho-directed halogenation of the anisole by the methoxy group is likely competing with the Pd-catalysed C-H activation, hence the lower relative yield.

[orgopete]

As I looked at this example, it appeared to be well crafted. Aromatic substitution occurred ortho to the methoxyl group. The palladium catalyzed reaction occurred primarily meta to the methoxyl group.  The question becomes what is the mechanism that changed the regiochemistry of the chlorination?

[phth]

Coincidently I was just reading about this type of palladium coupling.  What does the transition state look like?  Tell me and Ill give you another paper to get quant yield with the Pd²⁺ system.  It should lead you to the answer.

[Grimer]

Thanks a lot for the answers!

k1mng: You seem to be spot on. I talked with a professor about it and she pointed out that pyridin-rings are pretty common ligands to Pd-catalysts.

orgopete/phth: They're not to sure about all of the mechanisms since C-H activation is such a broad field and not as general as with most name reactions. But comparing with other reactions that I've read over the last couple of days, Pd probably first binds/coordinates to N, adds in between the C-H because of it being in the proximity (more than any electronic reasons) maybe in the process kicking out H with a ligand (happens in a lot of other cycles), oxidative addition with Cl and then reductive elimination/kicks out the substrate now with a Cl. Seems to add up with AcOH or base to recycle the catalyst.

[phth]

http://dx.doi.org/10.1016/j.molcata.2013.01.011

[k1mng]

I think it's difficult to discern mechanisms for organometallic complex catalysed processes decisively as they often progress reactions in a number of ways, but I think you've got the general idea for what happens Grimer!

One possible mechanism is that, following coordination by the pyridine, the Pd centre also coordinates (η²) to the nearest aromatic C=C on the anisole ring. The palladium centre subsequently oxidatively adds across the C-H bond (Pd[II] Pd[IV] in this step) and then reductively eliminates AcOH immediately to regenerate active Pd[II]. Then we get NCS oxidatively adding (again, Pd[II]  Pd[IV]), and then reductive elimination of the Ar-Cl product (Pd[IV]  [II]). Free acetate can ligand transfer with the succinimide anion (later reprotonated by AcOH) to complete the cycle.

Sorry that I haven't drawn this out, I'm not patient enough to use chemdraw for catalytic cycles..