Organic Achievement of 2006: Pd(IV) Intermediates Might Not Be That Rare

April 27th, 2007

The Chemmy Award for Organic Achievement of the Year goes to:

Melanie Sanford (Michigan) for establishing that Pd(IV) intermediates are important in at least one class of catalytic C–H bond activation reactions

I had decided on the recipient of this Chemmy a long time ago but procrastinated on writing the citation. This weekend, commenter “tuna fish” mentioned that Dr. Sanford might be moving to Yale or Caltech, and while I have no idea if this is true, the comment reminded me of my fondness for her work and that now is as good a time as any to write about it.

First off, trying to “contain” the Chemmy achievement awards in the various chemical disciplines to one year (here: 2006) is going to be difficult, because cool discoveries often take time to develop and get noticed. In this case, Sanford’s C–H activation work can be traced back to 2004. It was only last year, however, that the picture became clear (at least, clear to me).

When I learned organometallic chemistry—way back in 2002—we were essentially taught never to invoke Pd(IV) intermediates in our mechanisms.  Pd(IV) was simply too energetically-inaccessible to be relevant in most cases. Along these lines, I witnessed the merciless ridicule of more than one student by the teaching staff for using Pd(IV). Instead, good boys and girls used the Pd(0)/Pd(II) couple in their mechanisms.

In 2004, Sanford came along and published a simple case of catalytic, chelate-directed C–H bond oxidation:

Instead of outlining a mechanism that shuttled back and forth between Pd(0) and Pd(II), Sanford proposed a mechanism involving Pd(IV):

Naughty!  Or so I thought.  A subsequent study essentially extinguished all doubt that the Pd(IV) mechanism was correct. In this 2005 JACS comm., the Sanford crew hypothesized they could change the system to stabilize the Pd(IV) intermediate, found they could actually isolate it, got a crystal structure showing that it was indeed a Pd(IV) species, and then showed that heating it gave the same types of products that they saw in reactions where the intermediate could not be isolated. Crystal structures are the closest thing we can get to having incontrovertible photographic evidence of what molecules are actually doing, so you can’t really argue this one.  Score one for Pd(IV).

I know a lot of the hardcore synthesis crowd isn’t enamored with this sort of C–H activation chemistry because it is chelate-directed, which limits the scope of the reaction. That’s true, but what makes this batch of work so interesting is not the synthetic utility as much as the scientific value. We gained a new appreciation for the mechanism at play in these reactions and had to reassess a long-held notion of what isn’t reasonable.

So, congratulations to Dr. Sanford and coworkers. Enjoy your Chemmy and keep the good work coming.  And if any of you donkeys out there thinks there was someone else more deserving of this award, feel free to register chemmeow.com and start your own damn blog.

Previous Comments

  1. ZAL Says:
    April 27th, 2007 at 3:02 am I remember having attended a talk of her at my old university, a couple of years ago, which was very good. When she presented the Pd (IV) intermediate many people, in particular those unfamiliar with her work (including myself…at that time), were quite shocked, and you bet many questions were asked at the end of the talk. She gave convincing answers, though, and I could just imagine how proud of that crystal structure she was. True, she needs directing groups to do the chemistry, but world’s still not perfect. IMHO, a well-deserved award!
  2. Matt J. Says:
    April 27th, 2007 at 8:20 am Absolutely well-deserved. I briefly flirted with the idea of going back to grad school and working for Dr. Sanford. But then I decided I REALLY didn’t want to go to Michigan, nor did I want to go back to grad school.Congratulations to her group. Good pick, Paul.
  3. provocateur Says:
    April 27th, 2007 at 8:47 am SN2 on a sp2 center….kemistry has changed…
  4. Paul Says:
    April 27th, 2007 at 9:34 am To be precise, I should have put “SN2-like”, which is the term used in the paper.Edit to add: Done.  And going back to the paper again, I agree with you in that I’m a little surprised that they didn’t call attention to the idea that the orbital geometry would presumably not be optimal for any sort of concerted nucleophilic attack, considering all of the molecules in the substrate table were aromatic.  By the time the 2005 paper was written, they exlcuded the nucleophilic attack from their mechanism, favoring reductive elimination either directly from the octahedral complex or from the complex where the nitrogen ligand had dissociated first.
  5. Uncle Al Says:
    April 27th, 2007 at 12:30 pm If Pd(IV) organic mechanism is dogmatically and politically unacceptable, how is a supportive crystal structure consequential? Pd-catalyzed displacive chemistry on sp2 centers is heresy given 19th century eternal truths. It should be purged from the literature under Homeland Severity imprimature.Empirical evidence cannot dictate limits upon faith! “Poenitentiam agite adpropinquavit enim regnum caelorum”! Be small or God will crush you smaller.

    (Uncle Al just freaked two Mormon missionaries by answering the door in a Halloween mask. Feelin’ good!)

  6. aa Says:
    April 27th, 2007 at 7:51 pm hahaha the aversion to Pd(IV) has always struck me as a little strange… i remember once when a group mate presented a weird reaction he had found to a visiting professor of some renown. My friend was in the process of ruling out some mechanisms and put a few of the possible ones on the board. As he was drawing the intermediate involving Pd(IV) (this was in early 2005 if i remember correctly)the prof said “Ummmmm, you just drew Pd(IV) you know?” in the same tone of voice someone at a party would use to let you know you left your fly open. Discreet embarassment. As it turned out, it seems the Pd(IV) mech was incorrect, but hopefully now thanks to Sanford (and Daugulis) these intermediates will be more socially acceptable haha
  7. eugene Says:
    April 27th, 2007 at 8:59 pm This is a little similar to the whole Schrock/Katz dispute about Fisher carbenes and their participation in metathesis. Schrock had more dirt to throw and it stuck. However, he turned out to be wrong later. But in the end, Katz doesn’t have the Nobel. Personally, I’m not going to be satisfied until some sort of public apology from the Schrock camp.The whole thing about Pd(IV) is a little strange to me since if you start off with Pd acetate and you have oxidation, anyone who knows any organometallic chemistry of platinum which is just below palladium, shouldn’t have trouble accepting Pd(IV). The intermolecular nucleophilic attack is taken directly from that as well. Really, we should be thanking Bercaw/Labinger and Shilov for this one as well. Before Sanford, Pd(IV) was proposed as an intermediate by people in the groups of (or perhaps the great ones themselves) Trost and Canty and by others informally.
  8. provocateur Says:
    April 27th, 2007 at 10:36 pm i am not sure trost likes Pd(IV).I hv heard tht sanford got smirked at when she had submitted her proposals for these directed functionalizations.But I really find all this made-up hostilities towards mechanisms.We draw so many dotted lines as we please on transition states models to explain all those reactivities/selectivities.It seems when you draw dotted lines , you escape and when you draw a bold line you get screwed…
  9. eugene Says:
    April 28th, 2007 at 12:51 am Oh, you mean like “fuzzy bond theory”. When you draw a lot of dotted lines to cover up for the fact that you don’t know what the hell you’re talking about?
  10. milkshake Says:
    April 28th, 2007 at 7:07 am I think Milstein was invoking Pd(IV) in his pincer tridentate complexes catalyzing Heck long time ago (the argument was that there is no way these stablecomplexes fall apart to form underligated Pd species)
  11. Cat Herder Says:
    April 28th, 2007 at 10:24 am The term “tentatively propose” can go a long way in these instances, even if it IS a total cop-out. One has to walk a fine line between having people read and consider your work and being the subject of academic ridicule.
  12. Anonymous 10 Says:
    April 28th, 2007 at 3:32 pm God will have the last laugh Al.
  13. Wolfie Says:
    April 28th, 2007 at 8:43 pm How about Pd-Pd triple bonds ? Are there any ? What impact will they have on your girl-friend, Paul ?shit, i forgot he has no published record there
  14. Paul Says:
    April 28th, 2007 at 8:57 pm Wolfie, what have you been smoking tonight? Your comments are making less sense than usual.
  15. Wolfie Says:
    April 28th, 2007 at 9:19 pm i don’t comment anymore to any failed Harvard student, except he can name the right winethis one was Domaine Weinbach, Sylvaner 2005, bought at 67th wines in NYC, just a block away from the Met

    Weinbach has three stars in Bettanes et Dessauves, it’s like the Michelin guide for wine

    do you know Michelin ? except for tires, of course

  16. Wolfie Says:
    April 28th, 2007 at 10:45 pm na denn eben nich, geh halt ins Bett, lieber Paul und trink keinen schlechten Whiskey mehr
  17. Wolfie Says:
    April 28th, 2007 at 10:46 pm it’s a strange world, isn’t it ?
  18. eugene Says:
    April 29th, 2007 at 12:11 am Kind of hard to get drunk on crappy German white wine, but Wolfie managed to do it. Who the hell drinks Sylvaner anymore anyways?
  19. Shrug Says:
    April 29th, 2007 at 10:22 am I’m actually starting to wonder whether Paul is the man behind the Wolfie mask… ;-)
  20. eugene Says:
    April 29th, 2007 at 12:58 pm Nah, Paul can’t speak German, so there is that. For some reason, Wolfie is a really good troll that gets people to respond to him and derails the thread. I tried not responding to Wolfie, but he’s a little fun and it’s hard to ignore the troll when the blog chief doesn’t do so as well.Speaking of the thread, I’ll have to search for Milstein’s Pd(IV) proposal in Heck coupling. Thanks Milkshake!
  21. inside Says:
    April 29th, 2007 at 4:33 pm Pd(IV) species known for years. Crystal structures and all. she doesn’t reference them.
  22. excimer Says:
    April 29th, 2007 at 7:01 pm Inside,Such as? Inquiring minds are dying to know. Put up or shut up.
  23. excimer Says:
    April 29th, 2007 at 7:06 pm and other cliches as well
  24. Paul Says:
    April 29th, 2007 at 7:52 pm A line from the first paper reads:“While the Pd(0)/Pd(II) couple is more common in catalysis (refs), Pd(II)/Pd(IV) cycles have been implicated in benzene acetoxylation reactions (2 refs-a book by P.M. Henry and a paper by Crabtree).”

    And in fairness, this Chemmy is not for the discovery of Pd(IV), but for providing evidence that it is not as rare as previously thought.

  25. excimer Says:
    April 29th, 2007 at 8:15 pm A breezethrough of the Crabtree paper implicates Pd(IV) reasonably but makes no mention of isolating a Pd(IV) intermediate. (I don’t have access to the book right now.) I was wondering who else has isolated and characterized Pd(IV) complexes.From Eugene’s comment, I’m also curious why Pd(IV) is so rare (or is it?) but Pt(IV) is not. I could do some handwaving but does anyone have a good, like, thermodynamic reason why?
  26. eugene Says:
    April 29th, 2007 at 8:43 pm I don’t think Pd(IV) is rare. It’s probably an intermediate in many a catalytic cycle. I’d like to hear your hand-waving reasons though. Mine is that the atom has more inner electrons to shield the nucleus and it’s easier to stabilize the higher positive charge. Just one that I can think of off the top of my head. However that trend doesn’t hold throughout the periodic table so… Pt(II) is definitely a lot easier to oxidize with all other ligands being equal, but the resulting species is also a lot harder to reduce. Pd is really easy to reduce. Which is why, if you start with Pd(II), you’re screwed. The experience of walking into the lab next day to find fine black particulate floating in your reaction mixture can be very depressing if it happens with regularity as it does for Pd chemists. I don’t speak from personal experience of course. Just some people I know…But in defense of the ‘inside’ poster, I remember doing a literature search earlier and seeing examples of Pd(IV). However, these were synthetic organometallic references and had nothing to do with a proposed catalytic mechanism. There is no reason why Sanford should have to reference them. On the other hand, they would only back up her claim and not weaken it. There was even a reference to Pd(VI) that I found with strongly electron withdrawing ligands. Obviously, I don’t have access to SciFinder right now from the ‘Casa of Chemistry Nerdity’ and I don’t want to use remote desktop in case anyone might still be in the lab.
  27. bostoner Says:
    April 30th, 2007 at 12:40 am inside is right. look into jin yu papers at brandeis. he did this at the same time as sanford and gives all refs for pd-4 crystal structures. several were published before, can’t find them referenced in sanford paepr.
  28. provocateur Says:
    April 30th, 2007 at 8:25 am prof. sanford’s case is weakening for the chemmy…i think she shd hv referenced previous crystal structures of Pd(IV)if tht was her sellin point.
  29. bad wolf Says:
    April 30th, 2007 at 8:13 pm Dr. Sanford may be the answer to a rumor I heard ages ago. My old faculty was doing a candidate search 2002-2003 and I heard that a (unnamed) female candidate at the time had an absolutely SUPERLATIVE recommendation from Grubbs.I expected someone at a top-10 school but the time and pedigree match. So maybe its no surprise to the ‘powers that be’ that she’s such an up-and-comer.
  30. eugene Says:
    May 1st, 2007 at 7:45 pm Okay you tossers (#27 and 28), here are just two of many references to Pd(IV) crystal structures before 2004:http://pubs.acs.org/cgi-bin/ar…..30170v.pdf

    http://www3.interscience.wiley…..3/PDFSTART

    The point is, they are irrelevant unless you’re proposing that they they are catalytic intermediates. If you can isolate a Pd(IV) that sort of looks like what you would have in an actual catalytic reaction… then you have basically what the Sanford group has accomplished. Reference number 2 from Andjewandte actually mentions that Milstein proposed Pd(IV) intermediates in some catalytic reactions when he was a post-doc with Stille. Probably he proposed it for the so called ‘Milstein’ oops… I mean ‘Stille’ coupling. Still, the evidence he obtained back in the late seventies wasn’t that convincing. Which is why Sanford had a bit of a hard time of it at the beginning.

    The only thing I’ll give you is that probably Jin Quan Yu would have won the chemmy for this if he had started a couple of years earlier. But he didn’t.

  31. eugene Says:
    May 1st, 2007 at 9:02 pm Er… I didn’t mean ‘you tossers’. I meant to say “you t…wo”, um… “you two”. Yeah, I gotta watch my language. Sorry about that.If you must know, it’s because I’m re-playing Fallout 2 (after I heard the news that Fallout 3 was going to be released) so until I finish, unseemly language might crop up into my posts. Just wait until I start doing jobs for the mob in New Reno and get all of post nuclear war North California addicted to Jet though. What a great game.
  32. excimer Says:
    May 1st, 2007 at 11:37 pm I never really got into Fallout. Maybe I should play it again.Thanks for those refs, eugene.
  33. Pavs Says:
    May 18th, 2007 at 10:37 am MS is great, really enjoyed her presentation at Imperial :) Pd(IV) is like Cu(III), although stable Cu(III) was recently observed by RI-NMR in JACS
  34. eugene Says:
    May 18th, 2007 at 3:08 pm I’m not that sure exactly how these two metallic ions are similar since they have a completely different electron count, and are located in different rows (not to mention columns) of the periodic table. First row metals can adopt some really high oxidation states however. I’d like a reference to that JACS article too please. I guess I could go SciFind it as well.
  35. Anonymous Says:
    May 18th, 2007 at 3:12 pm The Cu(III) article is on JACS ASAPS (posted yesterday, I believe)
  36. Pavs Says:
    May 19th, 2007 at 5:15 am Well what I actually meant was that the stories of Pd(IV) and Cu(III) are kinda alike (properties etc R different). Although around 30-40 Cu(III) complexes are outthere, Cu(III)species in “organocopper” variant are only to be unravelled. the link: http://dx.doi.org/10.1021/ja067533d.Concerning Dr Sanford: I mean it takes real courage to have several works published b4 she eventually shows that Pd2/4 is the right thing with Pd(IV)complex structure. Anyway UMich is her first post. CONGRADS
  37. ChemBark » Blog Archive » Wrap Up: The Princeton News and Related Issues Says:
    August 2nd, 2007 at 12:02 pm […] Finally, let me also point out that there are plenty of positive posts on ChemBark, too (1 2 3 4 5). A lot of people conveniently forget that. […]

One Response to “Organic Achievement of 2006: Pd(IV) Intermediates Might Not Be That Rare”

  1. Organometallic chemist Says:

    As an organometallic chemist, I was always confused why some organic chemists make such a big fuss over Sanford’s Pd(IV) mechanism. Now it seems clear to me that some of you were taught that it’s ridiculous to propose any Pd(IV) mechanism. Well, perhaps the teachers should be blamed for their lack knowledge in organometallic chemistry.


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