Blog Carnival: What the Cope Rearrangement Taught Me About Chemistry

by James

in Organic Reactions

Note: to celebrate the International Year of Chemistry 2011, there’s a blog carnival going on. This is my contribution. If you can’t follow the structural details, hopefully the story tells itself without the pictures. You can find the other entries by searching the #chemcarnival hashtag on Twitter – JAA

One day in the mid 1990’s at some random undergraduate institution, a bespectacled, soft-spoken organic chemistry instructor wrote this reaction on the board.

“This is called the Cope rearrangement”, said the instructor. “It’s a rearrangement of 1,5- dienes.” I’m slouching in the front row of this class and to be honest I don’t see the point of this reaction.  To me, this looks like the most useless transformation ever: the product and the starting material are exactly the same.  This is not even flash-card worthy. Little did I know that this “useless” transformation had a lesson to teach me.

Flash forward several years later : working as a research assistant in an organic chemistry lab. We pack up in a car and drive across town to see a talk by a prominent organic chemistry professor. I’ve been an organic chemist for like, two weeks, and I’m not getting most of it. After the intro, the lecturer begins by saying,  “We just discovered a new oxy-Cope reaction. Now, I know what you’re thinking – “wait a second – didn’t Leo Paquette do all of those?”. Uproarious laughter from the crowd.  Killin ’em!   I don’t get the joke,  but I got the implication: I was now a part of a community where everyone spoke the same language and had the same background knowledge, and to fit in, I should know as much about  organic chemistry as possible so I can understand what the hell these people are laughing about. And I needed to learn about this Leo Paquette guy.

Leo Paquette, rocking the anionic oxy-Cope

Several months later, after some courses and a lot of reading,  the beauty of the Cope rearrangement was becoming apparent to me.  The reaction we were fed back in undergrad was only boring because the ends were the same, leading to a degenerate reaction of two molecules in equilibrium.  Where the Cope rearrangement can find use is in systems with a lot of ring strain, which means that one variant will be favored.

There’s even a molecule called Bullvalene, which doesn’t have a fixed structure: it spends eternity Cope-ing with itself. Wild.

What’s particularly useful is the oxy-Cope variation, where an oxygen is bonded on the 3-position of the 1,5 diene. Rearrangement in this case leads to the formation of an enol, which tautomerizes to the ketone. This gives you about 7 kcal/mol or so, enough to drive the equilibrium forward. The oxy-Cope can be used together two complex fragments: you can start with an alpha-beta unsaturated ketone, add a vinyl Grignard to it, allow to warm, and you’re done (versions like this where the oxygen is anionic are particularly fast). One of the coolest variations is when it’s combined with the Diels-Alder reaction to transform bicyclic ring systems into fused rings.

For several years, the Cope rearrangement  was something I’d only read about in a textbook and the chemical literature. I knew all about it but had never done one: like an exquisite wine that I’d read about but never tasted. About 3 years into my Ph.D. project, I was working with a funky ring system that was behaving strangely. As I left it in the NMR tube overnight, its peaks slowly disappeared, to be replaced by new ones.  The whole process screamed out “unimolecular rearrangement”. And to make a long story short, that turned out to be the case.

Wanting to know more about this process, so I measured the integration of the signals by NMR. And I got this graph.

It’s hard for me to explain what a tremendous feeling it was to plug in the numbers and get a graph like this, a beautiful curve.   I know, I know – it’s what you’re supposed to get – unimolecular decay, everyone learns it in gen chem.  But to get data, fit it in a curve, and get a half-life out of it, that was extremely rewarding. Something abstract, which I’d read about in a textbook, had become concrete – and I wasn’t following any lab manual or procedure. It was the natural pattern of the data I was collecting.

I don’t think any number of lectures, lab sections, videos, or inspiring lecturers can ever truly capture what it’s like to have an experience like this. It’s something you just have to discover for yourself. The Cope rearrangement drove home for me that there is a beautiful order in the way that nature works, and we can uncover it through recording and charting our observations. And it also inspired me to know more about organic chemistry so that I wouldn’t be left out of the inside jokes.

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{ 3 comments… read them below or add one }

Curious Wavefunction

What a great post! The Cope is indeed a deceptively simple reaction which hides surprising riches.



Thanks! I was actually going to do combustion, but you beat me to it. Leave it to you to write a post about the big picture.


Shreya B.

Thanks James, this is super helpful! Fun fact: Maitland Jones (who named Bullvalene, which you referenced above) is my current orgo professor. My final is on Tuesday… pray for me (your reaction guide has been hugely useful this week)! SB


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