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DBL%20Hendrix%20small.png College chemistry, 1983

Derek Lowe The 2002 Model

Dbl%20new%20portrait%20B%26W.png After 10 years of blogging. . .

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek email him directly: derekb.lowe@gmail.com Twitter: Dereklowe

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December 17, 2007

Le Dernier Cri

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Posted by Derek

There are plenty of chemical reagents and reactions that go in and out of fashion over the years, and even entire elements. For the last couple of years, it’s been gold – ten years ago, gold-catalyzed reactions were a backwater, and now they’re all over the literature. (Catalysts are the way to go; reactions that need excess gold to run are unlikely to catch on). Hardly an issue of Organic Letters goes by these days without some gold-catalyzed cyclization in it. But there are some elements that have never been in fashion, and odds are that they’re never going to be.

Tellurium comes to mind. It does some interesting reactions, and if it wasn’t rather poisonous and if its compounds didn’t stink beyond the ability of anyone to stand them, I’m sure that we would have discovered even more. But it is and they do, and there’s no way to stop either one, so no one’s going to make the effort any time soon. It’s the stench that really seals the deal, actually. Poisonous we work with all the time, but you don’t come across stuff that smells like organotelluriums very often, or so I hear. I’ve never had the pleasure myself.

And as for lab fashions, it’s also safe to say the day of the heavy metals is past. Mercury has a long, long pedigree in both organic and inorganic chemistry – back to the alchemists, actually. Everyone figured that there must be something special and/or magical about a metal that’s liquid at room temperature. They were right, in a way. Mercury does a lot of interesting reactions which are still taught in sophomore organic classes and are still run once in a while. I’ve done a few organomercurations myself, but most of them were years ago in grad school. I’ve only reached for the mercuric chloride once or twice in the last twenty years. That’s doubtless because I’m in the drug industry, but I think that the general use of the element has been trending down because of waste disposal issues. Lead, for its part, never had as much use in the art as mercury, and will probably never get the chance.

It’s not just the heavy metals, either. Beryllium is probably one of the most underused elements in the whole periodic table, as far as organic chemistry is concerned. Considering its spot up near the light end of the periodic table, where all its neighbors are on every lab shelf, you’d think that there’d at least be something you could do with the stuff. But I can’t think of a single reaction I’ve ever seen that uses it. The element’s peculiar toxicity (which mostly seems to be a problem by inhalation) helps keep it out of the spotlight: no organic chemist has ever found a need for it that outweighs its disadvantages, and not many are motivated to try.

None of these are going to be the next hot thing. But what is? Gold’s turn in the organic chemistry spotlight will end at some point – for all I know, things are already slowing down. If I had to guess, I’d pick another candidate from the precious-metal crowd, and I’ll nominate iridium. There are plenty of iridium-based catalysts, but none of them are the absolute first thing a chemist reaches for. It wouldn’t surprise me a bit if the element turned out to have a number of tricks in it that haven’t been discovered yet. They should at least be worth some JACS and Org Lett papers, that’s for sure. . .

Comments (20) + TrackBacks (0) | Category: Chemical News | The Scientific Literature


COMMENTS

1. As You Lean on December 17, 2007 10:57 AM writes...

Its always seemed sort of cruel that the precious metals are the really useful ones.

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2. Iridium on December 17, 2007 11:07 AM writes...

I agree on the iridium front, although I think currently Crabtree's catalyst is generally the first choice for directed hydrogenations.

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3. eugene on December 17, 2007 11:45 AM writes...

Iridium already has plenty of JACS comms. It's the best metal for activating CH bonds -- the activation barriers are the lowest for a good range of ligands. Unfortunately, not much after that. Still, because of that, it's a really good metal to use in transfer dehydrogenation and transferless dehydrogenation (work of Alan Goldman from Rutgers).

It is a bit expensive to be used on an industrial scale though. Right now it's second to Rhodium, which passed it by and left it in the dust a few years ago.

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4. Plum Bum on December 17, 2007 12:56 PM writes...

Welcome to the MWRA, Derek. The drain limit for mercury in the greater Boston area is 1 ppm. The allowable level of mercury in the tap water is - wait for it - 2 ppm. Ta da! Running the tap could put you in violation.

Needless to say, we no longer use mercury reagents under any circumstances.

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5. MTK on December 17, 2007 1:47 PM writes...

Indium seemed to be in fashion a few years back, but not so much anymore. In = MySpace, Au = Facebook.

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6. frenchchemist on December 17, 2007 2:09 PM writes...

What about iron???

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7. Jose on December 17, 2007 2:20 PM writes...

Furstner published some really slick Fe couplings a few years ago, but I haven't seen anyone use it in T.S....

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8. Hap on December 17, 2007 2:33 PM writes...

Other than Furstner? (I think he's used it in amphidinolide syntheses). I think there was a JACS comm. in the last month with catalytic iron and Grignards, but I can't remember what reaction it is.

Iron seems like a good choice - people don't like copper, the coinage metals are too expensive, and heavy metals are out. Manganese chemistry might be interesting too.

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9. Hap on December 17, 2007 3:21 PM writes...

You mentioned it before in one of the responses (to the above post, I think) but I thought that the use of tellurium is a showstopper not only because of its stink and toxicity but because of its persistence upon human exposure - if running a reaction with an aryltellurium reagent might get me 3-6 months on long-term disability (if I'm fortunate), I might think hard about alternative methods. Since no one else is going to want to make the target that way if the compound works, there doesn't seem like much of a point to using it.

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10. milkshake on December 17, 2007 4:52 PM writes...

organoberylium compounds can do some useful things: like allyl tin and alkyl indiums they work even in water.

The problems are: 1) Berylium is too expensive to be used as stoechiometric reagent 2) Berylium compounds are super-nasty contact allergents. The beryliosis you mention was typical for the nuke industry where people have been machining bulk quantities of metallic Be. The metal looks like "nicely behaved" light steel - it does not catch on fire and like with asbestos it takes long time for the symptoms of inhaling Be dust to show up, in a progressive lung damage. But I heard the nasty poison-ivy like reactions from soluble Be salts can develop rather quickly.

Oh, and the soluble Be salts have a pleasant sweet taste

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11. Jose on December 17, 2007 6:02 PM writes...

There is a research group in Brazil (Joao Comasseto in Sao Paulo) that does tons of organo-Te and Se chemistry. Some cool transformations, but why develop manifolds that *no-one* will ever use?

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12. processchemist on December 18, 2007 4:35 AM writes...

Mercury! A nightmare! The stinkiest reaction I performed on kilolab scale was using 2 Kg of yellow mercury oxide...

I'd like to see more work about iron, and I hope to see a Suzuki-based project coming to Phase I with the C-C couplig changed in an Iron catalyzed coupling of a grignard reagent.

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13. Stroom on December 18, 2007 6:25 AM writes...

There was an interesting review in Curr. Opion. Drug Disc. Dev. recently discussing the use of silicon moieties as structural elements in bioactive molecules (Franz, A. CODD&D, 2007, 10, 654-671.

Organosilicons are, of course, already very ubiquitous as protecting groups, as parts of synthetic intermediates, etc. Not too many companies that have had the stomach to push organosilicon compounds into the clinic though.

Sure there are plenty of elements which still need to find there place in catalysis...but for a medicinal chemist, it would also be nice with a few more building blocks to work with...C, H, N, O, S, P, X is starting to get boring!

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14. David on December 18, 2007 5:58 PM writes...

Reminds me of all the studies on various metals for anticancer drugs. After the success in platinum drugs for cancer (Carboplatin, Cisplatin and now Oxaloplatin and maybe Satroplatin), a number of other metal elements were tried in anticancer investigational agents. Tin, Titanium, Rheuthinium (SP?)and others. What was interesting to me is that every article and poster came from Germany. Seems they had a real interest in this..... But nothing has come of it.

David

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15. Carl Spackler on December 18, 2007 8:20 PM writes...

Re: 9

A lot of people don't know about things like manganese ....and chinch bugs.

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16. iChemist on December 19, 2007 12:35 AM writes...

I think both Derek and Jose (answer #11) got this one wrong. Yes, low molecular weight organotellurium compounds do stink, but the truth of the matter is that the most useful organotellurium reagents are pretty much odorless, and some even smell nice (I made several of these). These compounds undergo a variety of very interesting transformations, that would otherwise go unnoticed if weren't for the efforts of a few brave academic groups, Comasseto's included.

Just my 2 cents worth!

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17. jose on December 19, 2007 1:29 PM writes...

So, the stink goes away with increasing mw; does the tox also? If so, then I should reconsider my opinion!

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18. iChemist on December 19, 2007 9:17 PM writes...

H2Te and Na2Te are probably the most toxic tellurium compounds out there. If you ingest an organic telluride you may have a 'garlicky' breath for a few days or weeks. But as Derek pointed out, we work with poisonous compounds on a daily basis...

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19. Jonadab the Unsightly One on December 28, 2007 11:58 AM writes...

Chemists also work with sulfur all the time without batting an eye, because it has proven its usefulness many times over. I think, although they might complain about it, that they would brave the toxicity, the stink, and other hazards (explosiveness, radioactivity, whatever) if they had a general expectation of significant positive results from tellurium compounds.

But if nobody's really broken the ground, you sort of tell yourself that you don't know whether there's necessarily anything to be gained by such bravado. That's a large part of the difference between courage and foolhardiness: a fool takes chances for no very good reason.

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20. Jose on January 16, 2008 10:58 AM writes...

More Furstner Fe goodness just out.

J. Am. Chem. Soc., ASAP Article 10.1021/ja0777180 S0002-7863(07)07718-9
Web Release Date: January 16, 2008
Copyright © 2008 American Chemical Society

A Cheap Metal for a "Noble" Task: Preparative and Mechanistic Aspects of Cycloisomerization and Cycloaddition Reactions Catalyzed by Low-Valent Iron Complexes

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