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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: Twitter: Dereklowe

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January 17, 2014

A New Olefin Coupling

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Posted by Derek

Baran%20scheme.pngThe Baran group has published a neat olefin-coupling reaction which looks like something pretty useful. Building on heteroatom/olefin couplings from Boger, Carriera, and others, they use an iron catalyst and a silane to form carbon-carbon bonds between olefins, inter- or intra-molecularly. As long as you've got one olefin with an electron-withdrawing group on it, things seem to fall into place (no homocoupling of the other olefin, for example). Update: here are more details from the Baran group blog about how this reaction came to be.

I like several things about this setup: the reagents are easy to come by, for one thing (no nine-step glovebox procedure to make the catalyst). And they've taken care to run it on larger scales (by bench standards) to see if it holds up (that reaction of 14 to 15 was done on gram scale, for example). They've also checked and found that the reaction doesn't mind if it's under nitrogen or not, and that you don't have to dry the solvents. These are exactly the questions that people ask every time a spiffy new reaction comes up, and all too often the answers are "We don't know" or "Well, yeah, about that. . ."

The only thing that worries me, looking over the tables of reactions, is that there's only one with a basic nitrogen (where 3-vinylpyridine was used). Boc-nitrogen seems to be OK, but a lot of the examples are rather alkane-ish. I've no doubt that people will be testing the limits of the system soon, because it looks like a reaction worth running.

Comments (32) + TrackBacks (0) | Category: Chemical News


1. Chemjobber on January 17, 2014 10:47 AM writes...

The latest Baran lab blog post (google Open Flask Baran) is a funny, detailed discussion of the paper.

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2. Carmen on January 17, 2014 10:48 AM writes...

There's chemistry of a similar ilk happening just across the hall from Phil. His former student Ryan Shenvi reports an olefin reduction that gives thermodynamic products. DOI: 10.1021/ja412342g

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3. Henry's cat on January 17, 2014 12:24 PM writes...

That draft abstract is awesome. He's so superhuman and untouchable that he could have got away with submitting it...

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4. weirdo on January 17, 2014 2:45 PM writes...

I think it's somewhat telling that a post on a really cool chemistry paper like this has garnered all of three comments, while any post having to do Pfizer or Merck or jobs garners dozens.

What it's telling depends upon your point of view, I suppose.

Maybe we've forgotten why we studied chemistry in the first place. Kudos to Derek for blogging on this paper.

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5. Hap on January 17, 2014 3:33 PM writes...

Job talk is like politics a lot of the time - there's things held deeply and not necessarily subject to rational thought that motivate it and less (if any) requirement for quantitative analysis. Analyzing papers requires people to have read the paper and understand it. The resultant commentary is probably more like art appreciation than politics, but with added technical barriers and less motivation to anger.

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6. BCS on January 17, 2014 4:26 PM writes...

While I attest Baran's quality, I dont understand why we credit him as "superhuman" "untouchable" etc., We can also do chemistries like these if we are dedicated and pay attention to details.

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7. organichemist on January 17, 2014 5:37 PM writes...

I noticed that both Baran and Shenvi papers were published on the same day. Mn, Co, and Fe all have similar chemistry. Same silane reducing agent. I wonder if they are sharing ideas/projects?

I also question why the word "catalytic" is used in the article title when in most of the substrates not a single turnover would be realized for the yield that is obtained.

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8. Please on January 17, 2014 5:57 PM writes...

I agree. Let's admire Baran without attributing him with superhuman qualities. This is how it begins, this is what leads people to later declare certain individuals as untouchable and beyond the pale of even reasonable criticism. I am sure Baran will be the first one to quell this kind of hero worship.

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9. Ed on January 18, 2014 3:22 AM writes...

Yes, for a 'superhuman'' chemist his drawing skills sure suck!

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10. Anonymous on January 19, 2014 10:18 AM writes...

No doubt, this reaction will enable all us medicinal chemists to meet our drug candidate deadlines. We will use it everyday!

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11. Anonnymous on January 19, 2014 1:55 PM writes...

Very nice transformation, congrats to Baran group.. However, if you look at the SI, you'll see that almost all the reactions were run on very small scales, 10-30 mg, except the two gram-scale reactions. I think emphasizing the "gram-scale" aspect despite this situation is kind of misleading..

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12. Sili on January 19, 2014 3:15 PM writes...


How quaint.

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13. Anonymous on January 19, 2014 7:32 PM writes...

Nice method. Really JACS material? Well name helps.

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14. milkshake on January 20, 2014 3:55 AM writes...

It is definitely JACS grade, well above 90% (of the catchphrase-laden pretentious crap of no practical value that you so often see there). This is a reaction you may actually want to run, even as a medicinal chemist who has been brainwashed into running Suzuki and Buchwald arylations all thetime

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15. I have a Dream on January 20, 2014 9:42 AM writes...

@ Milkshake

Don't understand why you think this is a JACS material. It's a intramolecular Ene-Michael addition, been known since 80's with conventional Lewis Acids. Please refresh your memories with the work of Koichi Mikami and others.

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16. Student on January 20, 2014 10:23 AM writes...

Hey "I have a dream" or should I say ignorant troll. The literature you cite gives a completely different product outcome. This is legitimately a new reaction. If it doesn't belong in jacs please tell me what does.

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17. Anonymous on January 20, 2014 10:32 AM writes...

@ student

Tet. lett.?

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18. I have a Dream on January 20, 2014 10:50 AM writes...

@ Student

Like real innovative work!!!

I know its sounds real odd to talk abt Innovation & Organic chemistry, since these two don't go along very well lately.

For the sake of your time and the money that poor banker lend you for your graduate studies, PLEASE break open a book on GTL (please don't ask me what GTL means) and read abt it.

I really feel sorry for you mate.

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19. Student on January 20, 2014 10:54 AM writes...

Give the citation troll or crawl back in your cave.

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20. I have a Dream on January 20, 2014 11:36 AM writes...

@ Student

I know you are annoyed, You have probably googled GTL and came up with Gym-Tan-Laundry and didn't even bother to scroll down couple of citation to look for something relevant to what you do.

With your kind of attitude, There is no one to save you from ignorance you live in.

Best of luck finding a job...

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21. Derek Lowe on January 20, 2014 12:05 PM writes...

#20, IHAD:

Fine, you know about iron-catalyzed gas-to-liquid technology. For all I know, you used to work for Sasol. But do you have a citation that anticipates a selective bench-scale reaction like Baran's paper?

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22. I have a Dream on January 20, 2014 1:37 PM writes...

@ 21 Derek Lowe

May be May be not. Derek..I know that you know revolutionary technology like these remains Trade secret for most part. I also know that you know in a capitalistic driven society we cant expect someone to release their next billion dollar idea out to public with no incentive in place.

But, There has been significant effort placed by narrow minded individuals and fringe dwellers to redefine the true meaning of innovation. Its unfortunate that the younger generation would have to cope up with all these. Some understand and come out of it in time while most don't.

I use to be a hard core organic chemist. To what ever my word may worth, true opportunity for innovation is most likely to reside outside of organic chemistry NOT inside

btw...Shell & Dow chemicals are way ahead of Sasol.

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23. polybus on January 20, 2014 4:56 PM writes...

There's a heck of a difference between 600 C and 60 C, especially when trying to make chemicals that have to meet a spec better then "can pour from a bottle and burn".

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24. gippgig on January 20, 2014 5:54 PM writes...

Idle thought from a nonexpert: Could the EWG-bearing olefin be replaced by a carbonyl or imine?

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25. Old Timer on January 20, 2014 6:12 PM writes...

I reviewed this paper. It's legit. I was working on very similar chemistry when I received it to review. I was happy to see the interesting reactivity and, at the same time, pissed I didn't see it under very similar conditions!

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26. 92037 on January 23, 2014 11:09 AM writes...

@7 organichemist, I've seen Phil and Shenvi several times at TGI Fridays La Jolla late at night with a portable whiteboard and sharpie, while downing a few black and tans...

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27. milkshake on January 25, 2014 9:10 PM writes...

#15,20 IHAD: If you had actually bothered to read the Baran's paper, you would find out that this is definitely not "intramolecular Ene-Michael addition, been known since 80's with conventional Lewis Acids"

Because they do see this reaction too, in the absence of a good silane, and the product is DIFFERENT (hydroxy-substituted hydrindane, versus cis-decaline). So, please, STFU.

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28. I have a Dream on January 26, 2014 9:27 PM writes...

#27 Milkshack

Allrighty then, Spend rest of your life working on a minute differences between organic reactions. May be, thats all you are capable of doing or Perhaps, thats what you have always been thought as real innovation.

Since you are more than happy to live in your own little cave and obviously get offended by any out of box thinking, I will leave you alone in there to Jer*off

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29. milkcrap on January 26, 2014 9:50 PM writes...

@ 28

Solid reply. Several people writing here have some serious problems when it comes to assess progress made in the field of organic synthesis. Their will always be new reactions to discover. The problem is that it gives nothing of value anymore. Organic chemistry is now a tool and no longer a science. The real problems are in the energy field. The survival of organic chemistry depends on how chemists will be able to bash and criticize themselves not just by aiming at getting your work into jacs.

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30. Cheesecake on January 27, 2014 10:12 AM writes...

15,18,28 & #29. Hats off to you guys. It takes guts to look at your own work and be critical about it.
Its hard, but that's how you find true meaning in your life.

this blog is slowly becoming a hub for organic chemists to sit around, Jer*off each other and feel good about themselves how great the work they are doing. But, the truth is that it has been decades since any real innovation happened in organic chemistry.

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31. Anonymous on January 27, 2014 5:10 PM writes...

# 28,29 and 30

Tune it down dudes. You guys are rough on Milkshake and others. What if one day, perhaps, you are not able to take off a trityl group, or say a THP group. What are you going to do? It's guys like him, with their monumental knowledge and deep understanding of organic chemistry that will provide you an answer such has "have you tried to innovate by screening all possible acids".

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32. Anonymous on January 30, 2014 12:43 PM writes...

My spidey senses are telling me that Cheesecake, milkcrap, #31 Anonymous and Ihaveadream are all the same person wasting away on their computer trying to upset people on the internet.

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