The New Clayden pp. 1003 – 1028

p. 1004 — The nitrosoureas are known carcinogens.  They form DNA adducts (not sure exactly what they are) and are used experimentally to produce random mutations.  Could they be forming carbenes in vivo?

Also, how do you make N-Methyl N-nitroso urea?  N-methyl, N-nitroso toluene sulfonic acid?  

p. 1007 — I assume you make tosyl azide from tosyl chloride plus sodium azide

p. 1007 Rh2(OAc)4 — presumably the structure will be given in the next chapter. 

p. 1014 “Spin flipping, which can occur only through collision with another molecule (solvent usually) is relatively slow on the time scale of molecular rotations . . . “  Well how slow?  These numbers are known.  Why not give them.  Also why does a collision have to be involved for spin flipping to occur?  I think this question has been answered before.  Sorry about asking it again. How about another link to it. 

p. 1016 Interesting bunch of natural products containing cyclopropanes.  How does Nature actually manage their synthesis? 

p. 1018 — How do you make N2-CO2Et?  Possibly using the tosyl hydrazone?

p. 1023 — Metathesis at last.  When I type it, I have to stop myself from typing an awful word I’ve had to type (and utter) for years — Metastasis. 

p. 1024 — In the mechanism shown — why doesn’t the ‘carbene’ attached to Rh leave the Ru and form a cyclopropane with the other olefin? 

Also, all stereochemistry has vanished ! ! !

The catalyst goes from having 5 bonds to various things, to 6 with the bonds shown coming off the ruthenium atom like quills from a porcupine.  Surely the disposition of the bonds in space must be known?  Doesn’t it matter?   Ditto for the metathesis catalysts on 1025.  This is the way things were drawn (if they were drawn at all), in my orgo book of 54 years ago — English and Cassidy.

Hopefully the chapter on organometallics will be more enlightening about what is going on in metathesis reactions.  The discussion in this chapter takes me back to med school — this is what happens — remember it — never mind why.  At least in med school it was because no one knew why.  Here, perhaps they do but they aren’t telling.
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  • luysii  On November 25, 2012 at 7:15 pm

    Metathesis isn’t just academic. You can rigidify an alpha helix using metathesis [ Proc. Natl. Acad. Sci vol. 109 pp. 17942 – 17497 ’12 ] You place two amino acids containing omega olefinic side chains where you want (a feat in itself), 4 or 7 amino acids apart — so they’re on the same side of the alpha helix and then do a metathesis reaction with them. This locks the alpha helix in place. In this case it was used to make a peptide mimic which interacted with beta-catenin, a central node in the Wnt pathway which is important in many types of cancer.

  • Metathesisfan  On November 26, 2012 at 3:36 pm

    Hi luysii, yes, metathesis isn’t just academic. In our small company here in the Bay Area, we use it to make constrained macrocyclic peptides as enzyme inhibitors. In fact Grubbs would probably have not won the Nobel Prize if metathesis were merely academic; it has really revolutionized the production of polymers and drugs in industry.

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