The New Clayden pp. 1102 – 1133


In general, very good to see referrals to previously discussed material given as page numbers rather than chapter numbers as it was in the previous edition.  Also good to see that the Harvard and Princeton chemistry departments have people who have done very good work (Evans, MacMillan, Jacobsen).  

p. 1108 The top face of cyclopentadiene is shielded by the ethyl groups attached to Al.  In the second example, the Al isn’t attached to anything, presumably something like AlCl3.  

1110 — The trans enolate in the top line  would be less stable regardless of the orientation of the isopropyl group.  Once this is established, the orientation of the isopropyl group gives an incoming electrophile just one way to attack.  Essentially the oxazolidinone gives you a twofer.  A pleasure to see exquisite stereochemistry re-emerge after the previous chapter on organometallic chemistry. 

p. 1111 —  “less than a milligram of a chiral compound can be passed down a narrow column containing silica modified which  a chiral additive.”

1113 — The 3 dimensional visualization tools for sparteine given by the book’s web link is incredibly helpful, particularly since I don’t have a set of molecular models.  I used to use something called Dreiding models which were very good.  Apparently Aldrich still sells them, but I had trouble with their catalog.  Does anyone know if they’re still available?

1115 How is Tosyl 1,2 phenylendiamine (TsDPEN) actually made so that you get one enantiomer.  What is the chiral starting material. Or do they just crystallize it using an enantiomerically pure chiral compound?

1118 — Why does using ruthenium instead of rhodium broaden the number of substrates undergoing asymmetric hydrogenation.

1123 — What is the geometry of the salen complex of Mn shown at the top of the page.

1124 — It isn’t clear just where the Oso4 sits in DHQD2PHAL or DHQ2PHAL.  Perhaps this isn’t known?

1127 — If you use a different diastereomer of the chiral amino alcohol, do you get a different enantiomer of the product of the aldehyde with diethyl zinc? 

Out of order, but there are 3 great papers in the 26 Oct Science (vol. 338 pp. 479 – 480, 500 – 503, 504 – 506 ’12) on selective formation of one diastereomer or enantiomer using an asymmetric organometallic catalyst.  The first is particularly interesting as it puts a transition metal catalyst catalytic site of a protein.  Here’s some more about it

Streptavidin is protein produced by a microorganism (Streptomyces avidini) which binds biotin very tightly (Kd is 10^-15}. The binding pocket for biotin is large, and the authors hooked a Rhodium complex to the biotin via derivatizing a Rhodium pentamethyl cyclopentadiene ligand so it was covalently attached to the biotin. Then they threw a benzamide derivative + acrylamide at the protein metalloenzyme complex. Apparently everything fit within binding site for biotin within the streptavidin so they actually got out a dihydroisoquinolone. They achieved a 100 fold acceleration in rate (compared to the activity of the isolated rhodium complex) and even better the enantiomeric ratio was ‘as high as ’93:7. So this is aromatic C-H activation within the confines of a protein. Slick

The second paper is more general in that it uses a derivatized cyclopentadiene Rhodium L1, L2 system.  The cyclopentadiene is fused to a saturated cyclohexane ring with substituents hanging off it to create a steric environment such that the L1 (large) and L2 (small) are forced to lie in particular directions.  Then the reaction begins.

Very pleasant to realize, that after some 1100 pages of Clayden, I can read and understand very current research literature. 
Again, it’s worthwhile comparing this to what premeds are up against.  See

1128 — Organocatalysis — so that’s what MacMillian did to become chemistry chief at Princeton ! Clever stuff.

1130 — Showing that chiral auxiliaries aren’t just stereochemical navel gazing (although they certainly are elegant and worthy to gaze at), they were used 4 times in the synthesis of discodermolide.
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  • Aspirin  On November 12, 2012 at 3:13 pm

    Princeton has always lagged behind Harvard, Caltech, Stanford, Scripps and others in chemistry, and their current lineup and plans don’t inspire much confidence. To a lesser extent than MIT, Princeton has always managed to lose their star chemists to other institutions; examples would be Schleyer, Kahn and Walker.

    • luysii  On November 12, 2012 at 5:48 pm

      Possibly true. I haven’t followed the academic to and fro of the last 50 years. But it was a great place to get an undergraduate chemistry education. Schleyer was my undergraduate advisor, and I’d guess that all of his advisees had hours of contact with him each week — not necessarily sit down and one to one, but being within a few yards of him in his lab, asking questions as they arose, working late in the lab and going out for pizza when done. It was an environment where you lived and breathed chemistry. Hopefully this is still true.

      The department (as well as the university) is incredibly rich now so hopefully they’ll keep their newly purchased stars. For why please see

  • John Wayne  On November 13, 2012 at 11:01 am

    Looks like Aldrich doesn’t sell the Dreiding models anymore (they are discontinued). I have been pretty happy with the GHS models; not quite as good as Dreiding, but much better than those crappy ball and stick ones.

    • John Wayne  On November 13, 2012 at 11:02 am

      Make that ‘HGS’, they are manufactured by Maruzen.

  • Aspirin  On November 13, 2012 at 2:59 pm

    Being rich may not make a big difference since the university may have its own priorities. MIT is the classic case of a school that managed to lose one outstanding chemist after another to other universities – Roberts, Sharpless, Whitesides, and now Dan Nocera (to Harvard) – in spite of having ample funding. The simple explanation is that chemistry was just never as big a priority for MIT and Princeton as were other disciplines like math, physics etc.

    • luysii  On November 13, 2012 at 5:09 pm

      Aspirin — You really should look at the link. It’s my understanding that Taylor donated all the royalties from his work to the P. U. Chemistry department, so it won’t go anywhere else.

      I do recall the links between MIT and Harvard chemistry being pretty strong back then. Buchi would always come over to the Woodward seminars, bringing a bunch of MIT grad students along.

      Thanks for commenting

  • Aspirin  On November 14, 2012 at 3:24 pm

    Do you know what they are going to do with the money? They may well spend it on fancy new equipment rather than on hiring faculty. Not a bad thing by any means, but not the best strategy if you want to make Princeton competitive with Harvard and Stanford. The links between Harvard and MIT are strong indeed; that’s why so many MIT professors move to Harvard…

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