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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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June 4, 2013

The Flip Side: Organic Chemistry That Should Be More Famous

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Posted by Derek

I see that Neil Withers is trying to start up a new discussion in that "Kudzu of Chemistry" comment thread. The main topic is what reactions and chemistry we see too much of, but he's wondering what we should see more of. It's a worthwhile question, but I wonder if it'll be hard to answer. Personally, I'd like to see more reactions that let me attach primary and secondary amines directly into unactivated alkyl CH bonds, but I'm not going to arrange my schedule around that waiting period.

So maybe we should stick with reactions (or reaction types) that have been reported, but don't seem to be used as much as they should. What are the unsung chemistries that should be more famous? What reactions have you seen that you can't figure out why no one's ever followed up on them? I'll try to add some of my own in the comments as the day goes on.

Comments (25) + TrackBacks (0) | Category: Chemical News


COMMENTS

1. See Arr Oh on June 4, 2013 8:22 AM writes...

Air- and moisture-stable versions of highly-active catalysts. Grubbs-Hoveyda and Buchwald ligands are good starts, but let's see the same for Ni, Ag, Pt.

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2. Anonymous on June 4, 2013 8:55 AM writes...

I like organocatalysis, but (like a lot people) I'm tired of seeing papers publishing its use for the same types of reactions.

It would be prefer to read novel reactions that they catalyze rather than another Michael reaction for example.

Maybe the reason is that there are no other reactions they can be used for, but at the same time I'm not so sure people have tried hard enough to try and discover them.

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3. Hap on June 4, 2013 9:18 AM writes...

Enantioselective/stereoselective [3+2] cycloadditions (organocatalytic or otherwise) with reaction partners that aren't functionalized to the hilt or that possess functionality which doesn't take lots of steps to remove.

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4. Hap on June 4, 2013 9:38 AM writes...

It would help if I would read.

I don't know if it's all that good (high-yielding/generlly applicable), but Danishefsky's group's work on alternate Diels-Alder dienophiles is cool, as well as Hoye's enyne D-A (even if the necessary substrates have lots of gorp on them). Dienes that didn't polymerize when you blink at then but which can undergo activated D-A would be cool.

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5. ST on June 4, 2013 9:54 AM writes...

catalytic enantioselective NHKs that work on various substrates. The work out there is not enough and they do not really work yet

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6. Rock on June 4, 2013 10:14 AM writes...

Homogeneous asymmetric hydrogenation catalysts. They have been around for 30 years, work great, but most still require 100 atmospheres of pressure. Same chemistry but with a balloon, or even a Parr would be a huge advance.

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7. Anonymous on June 4, 2013 10:25 AM writes...

my colleague's paper looks like a good candidate for a "click" reaction: http://pubs.acs.org/doi/pdf/10.1021/ja400119t

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8. Hap on June 4, 2013 10:31 AM writes...

As long as the rest of the fluoros don't wander off unpredictably, it would be useful, and it seems cool.

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9. anon123 on June 4, 2013 11:00 AM writes...

'origin of life' chemistry

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10. Flatland on June 4, 2013 11:12 AM writes...

Enantioselective reduction using S. Cerevisiae. The selectivity of the enzymes always amazes me. Plus, it makes your lab smell like bread. I think its not used that often because scale-up and workup can be... interesting (hands down the worst emulsion Ive ever seen, but a big centrifuge and big centrifuge bottles fixed that).

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11. sha on June 4, 2013 11:52 AM writes...

@7 - looks very useful - what's up with that CD spectra though?

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12. Jordan on June 4, 2013 12:56 PM writes...

Organic chemistry that should be more famous? Solvent-free (or low-solvent) chemistry, and catalytic reactions using cheap metals. Both solve practical problems.

I note that both of these were cited as "kudzu" in the previous thread.

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13. Anonymous on June 4, 2013 1:15 PM writes...

@7: The original discoverer of that reaction (Schubert: Macromol. 2009, 42, 2387) did indeed refer to it as a "click" reaction.

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14. CMCguy on June 4, 2013 1:43 PM writes...

Even though there has been a few successful applications IMO it would be great to see much wider and more meaningful usage of enzymes and other biologic catalyst to make organic molecules, especially at large scales. There is a potential tool box there that most people ignore because lack experience and frankly is a large shift from the norm. I may be out of touch as this was a hot topic in the 80s although my impression is that many people working at that interface shifted focus to preparation of Biologic molecules as drugs and not as much on making chemical advances.

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15. Anonymous on June 4, 2013 3:34 PM writes...

@CMC-

Codexis would be quite happy to sell you (and anyone) screening kits to try out different enzymes for transformations (e.g. stereoselective transaminases or ketoreductases). The hope is once you find one that works, you'll be willing to pay to make a better one and/or they can sell you a bunch if/when your molecule scales up. It is hard to get chemists to try, though. Seems like only Merck has really embraced them.

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16. Anonymous on June 4, 2013 3:43 PM writes...

Catalysis and small molecule activation by the alkali earth metals and the actinides. Nice stuff.

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17. Nick K on June 5, 2013 1:18 AM writes...

#6 Rock: I've done many asymmetric reductions at 2 atm in a Parr shaker with Rh and DuPhos ligands. Worked beautifully, with S/C ratios of 5000 or more and ee's of >95%. The only really hard part is getting the reaction mixture totally oxygen-free. This would be on my personal wish list: an oxygen-tolerant asymmetric hydrogenation catalyst.

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18. GG on June 5, 2013 1:48 AM writes...

Truly probing the scope of new catalytic methods.

Most methodology studies are performed with commercial substrates, or ones available in a couple of steps...and then omit the ones that don't work. A method should be subjected to every organic functional group on the planet. This might not even be so hard, one doesn't need a substrate with all FGs; mixtures could also be tested.

Aldrich could sell the "catalyst annihilator kit". It would consist of a few vials: one with acidic functional groups, one basic, one strong chelators...and so on. With this information a catalyst's 'fitness' (in the evolutionary sense) for different chemical environments could be quickly characterized.

This kind of information would help me on a daily basis in my synthetic planning.

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19. sepisp on June 5, 2013 1:55 AM writes...

I never understood why people would use a flimsy balloon setup and a lot of catalyst when you could just set up the reaction in a high-pressure reactor with an industrially realistic catalyst.

Also, my earlier supervisor said that multicomponent reactions like Petasis should be used more.

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20. Anonymous on June 5, 2013 5:37 AM writes...


Oxidations.

In the earlier post about the “The Current Kudzu..” a lot of people were mentioning oxidations. I thought this was amusing because oxidations have been highlighted as a problem for the synthesis of drugs. See Carey et al. Org. Biomol. Chem., 2006, 4, 2337–2347. I realise that paper was from 2006, but they are still a problem.

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21. Secondaire on June 5, 2013 8:18 AM writes...

I second what was See Arr Oh said about air-stable ligands/catalysts. Gloveboxes aren't practical for medicinal/process chemists.

Also; good ways to make differentially functionalized quinolines, naphthalenes, naphthyridines, etc. without fancy gold catalysts or having to heat something to 230 ˚C would be pretty sweet.

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22. Jordan on June 5, 2013 11:02 AM writes...

I'll add another one to the list: flow chemistry. It is getting more attention these days, but probably still less than it deserves (based on its potential).

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23. Alex on June 5, 2013 1:03 PM writes...

Selective and especially not selecetive late stage fluorination. Not selective late stage methylation is also very desirable.

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24. Anonymous on June 5, 2013 1:08 PM writes...

How about anything that is remotely scalable and industrially relevant. Also, if a catalyst is involved, how about using loadings of 0.1 % and not 10-20%.

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25. Sisyphus on June 5, 2013 6:16 PM writes...

1) Organocatalytic cross-coupling reactions (no transitions metals required);
2) "true" iron catalysis;
3) sp3-sp3 cross-coupling reactions.

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