Monday, September 26, 2011

My favorite reaction: Grubbs' metathesis chemistry


Yet another chance to critique my structures...
It's pretty difficult to think of a reaction that's my "favorite", but if there's one that I think is pretty wonderful, it's the Grubbs' ring-closing metathesis. A few reasons:

Conceptual simplicity: While ruthenium-catalyzed metathesis (cross-metathesis or ring closing) is fairly mechanistically complex, the reaction (concept and retrosynthesis) is simple enough to teach to a sophomore. I suspect that its simplicity may be overly tempting to chemists; I've found myself led astray when planning syntheses in attempts to incorporate a RCM into routes.

Operational simplicity: It's pretty hard to think of an easier reaction -- degas, dump, dump, stir and heat. Filter through a silica gel pad, bam, there's your pure product.

Web 2.0: Olefin metathesis may be the only reaction that not only has a company, but it has a blog. All Things Metathesis is a great resources for, uh, all things metathesis.

Silly personal reasons: Like just about every other natural product synthetic route during the time that I graduated, there was a RCM in my thesis research. But there's a much more personal reason I feel a certain bond with Grubbs chemistry -- I found out that Professor Grubbs won the Nobel Prize while I was preparing to get married. (Earlier that month, I remember idly speculating about whether or not olefin metathesis had been around long enough to garner attention for a Nobel.) For some reason, it made my wedding and honeymoon just that much sweeter knowing that an organic (oh, okay) an organometallic chemist had won the chemistry Nobel.

If I could think of a single word to sum up Grubbs' metathesis chemistry, it would be "cool." And that's why I chose it for my favorite reaction.

Runners up: Haufe halofluorination, Fu's sp2-sp3 catalysts, the Finkelstein.

4 comments:

  1. @CJ: Better get used to running all of Fu's reactions on Pacific Standard Time....

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  2. For some reason, it made my wedding and honeymoon just that much sweeter knowing that an organic (oh, okay) an organometallic chemist had won the chemistry Nobel.

    Your wife must be a saint, or a chemist...

    ;)

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  3. I have a lot affection for the Grubbs olefin metathesis because Grubbs is from my hometown and went to my high school (years apart, of course). Plus olefin metathesis was the subject of the last cume I needed to finish with those (and I scored better than members of Chuck Casey's organometallic group).

    If I had to name my favorite reaction though I'd have to say Grignard - so useful, so easy. Diels-Alder for usefulness though it gave me fits in Synthesis class in grad school.

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  4. One of my most gratifying moments in grad school was when I finally tamed my cross methathesis (intermolecular, not ring-closing) reaction to form a trisubstituted olefin.

    Long story short, I needed to benzoate protect my homo-homo-allylic alcohol (not allylic alcohol, not homoallylic alcohol, but one more carbon away). This is known to help XM giving trisub olefins. Starting with the monosub olefin in solution led to dimerization with slow consumption. Starting with the G2 catalyst in solution led to catalyst decomp before the reaction completed.

    So the final reaction conditions were: G2 in toluene @ 80 degC. 5-fold excess of 1,1-disub olefin. Dropwise addition of both the monosub olefin AND the catalyst from separate syringes. Excess 1,1-disub olefin was recovered along with clean coupled product in a 45% yield and 2:1 mixture of cis/trans alkene isomers (separable by HPLC).

    All this on advanced material a dozen or so steps in.

    Man was I thrilled when that reaction worked.

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