Monday, October 15, 2012

Stump Your Friends! A Devious Diels-Alder

You may have noticed a lot of chatter about the "turbo-charged" Diels-Alder (Chemistry World, C&EN) recently reported by Prof. Thomas Hoye and colleagues at UMN. With all the fuss, another equally exciting, albeit subtler D-A development might have been overlooked.

Introducing: the metathesis-modified Himbert reaction!

Wait...the what?

Browse on over to Org. Lett. ASAP for a crazy two-stepper you're sure to love. Here's the opening scheme, so sharpen those pencils, and try some electron-pushing before I tell you the secret:


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Give up? I tried all sorts of pi-arene cyclizations, and drew out amide tautomers until my eyes bled. But the real answer, clues author Prof. Chris Vanderwal, lies 30 years in the past. A brief (2/3 page!) 1982 communication in ACIEE related a rare bird indeed: an unactivated benzene ring participating as a diene, with no added metal catalysts, pressure, acids, or bases. Upon heating, the tethered alkyne isomerizes to an allenamide, which gladly serves as the dienophile (somewhere, Richard Hsung is smiling).

Source: Himbert, Henn ACIEE 1982, p. 620
Vanderwal's insight comes next: seeing a strained [2.2.2] diene, he figures he can pop it open with some metathesis magic. A touch of Hoveyda-Grubbs, some ethylene, and a little heat rearrange the strained system to a complex 7-6-5 tricyclic lactam. His group prepares quite a few of these scaffolds, and hopes to utilize them to access several of the Erythrina alkaloids. 

P.S. First one to use this problem for 'mechanisms' group meeting wins!

9 comments:

  1. Hah, I tried doing the Diels-Alder first, retrosynthetically speaking, since the cyclohexene was staring me in the face. Gets back to a polyene that could've come from ring-opening metathesis of the phenyl ring (?!) with ethylene. Whomp. Cool stuff!

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  2. Now you know why I never took Chemistry. However, after taking Physiology and finding out that I was wrong not to study it, I plan to study it now in my old age. I found that I loved what Chemistry I had to study and I was good at it, so, someday, I hope I will understand what the question and answer meant. It is blogs like yours that make me realize Chemistry is fun and since I can only understand things in 3D after translating them from 2D, maybe I won't be so bad at it after all.

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  3. Loved this. Chris and I are both Sorensen lab alums, though we didn't overlap. So great to see him pull a paper from the past to explain cool chemistry. Apropos for the former student of a "Classics" author.

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  4. Is there any reason you couldn't use the same trick to get thiophene to act as a diene with an alkyne in a Diels-Alder?

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    Replies
    1. @Bend - Looks like Prof. Himbert tried these exactly once, in Chem. Comm, 1990
      http://pubs.rsc.org/en/Content/ArticleLanding/1990/C3/c39900000405

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    2. Interesting. Thanks.

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