The New Clayden pp. 852 – 876

This is a great chapter, showing what I think are state of the art stereochemical control mechanisms in actual natural product syntheses in the literature.  It’s exactly why I’m reading the new Clayden before trying to read blogs like Totally Synthetic (to get up to speed with what’s going on now after reading the first edition). Probably the syntheses presented at chapter’s end are at the graduate level, but they use nothing that hasn’t already been discussed.

One of my musician friends asked, what I was going to use the math I’m reading for.  We’d just finished playing a great Dvorak piano trio and I told her the same thing we used the trio for.   To me, at least, it’s all the same.  I get esthetic kicks from music, math and clever organic syntheses.  The quality of esthetic pleasure is differs among the three, but it’s esthetic nonetheless.

p. 854 — “For a stereospecific alkene transformation, choose the right geometry of the starting material to get the right diasteroisomer of the product.   Don’t try to follow any ‘rules’ just work through the mechanism.”   Amen.  Let it be a sign on the doorposts of thy house.

p. 856 – 857 — I’m not trying to be obnoxious, but the discussion of prochirality seems to embed what is simple stereochemistry in a plethora of unnecessary terms. 

p 859 – 860 — It’s clear from the level of discussion of the conformations of phenyl methyl acetaldehyde, that the book was written by multiple authors.  This particular author is addressing the first time student (or at least this part is).  Nothing wrong with a little hand holding in an elementary textbook. 

p. 861 — ALthough Dolastatin is said to be ‘one of the most powerful anticancer agents known’  it isn’t in clinical use.  It inhibits mitosis, so probably side effects kept it away from the bedside. 

pp. 858 – 865 — The discussion of stereoselectivity, Felkin Anh, chelation, electron donating substituents on the alpha carbon next to the ketone is elegant.  You don’t have to memorize anything — just think.  However, all is so well explained, that it’s unlikely that there is further research to be done on the subject, except when you’re trying to make something new.  

p. 865 — Any ideas why the lowest energy conformation of the carbon next to a double bond has one of the atoms attached to this carbon in the plane of the double bond (e. g. eclipsing the double bond).  Ken Houk was impressive as an undergraduate, and was already solving problems in the (subsequently legendary) Woodward seminars.

p. 872 — The synthesis of methyl mycaminoside with 5 asymmetric centers in a 6 membered ring, and reminds me of Woodward’s synthesis of reserpine, which also has 5 asymmetric centers in a 6 membered ring.   Particularly nice the way the synthesis used many of the stereochemical principles seen earlier in the chapter. 

p. 875 — I don’t see how the stereochemistry of L-isoleucine is preserved when the NH2 group is diazotized and then replaced by OH.   Well, I didn’t see it at first reading, but a few paragraphs later it was explained.  Shows that I’m still conscious I guess. 
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  • Curious Wavefunction  On September 18, 2012 at 12:25 pm

    “Any ideas why the lowest energy conformation of the carbon next to a double bond has one of the atoms attached to this carbon in the plane of the double bond”

    The reason, while not entirely unambiguous, has to do with the fact that two C-H bonds would be gauche to the C=C orbitals in the “intuitive”, non-eclipsed conformation. This destabilizes this conformation relative to the one which eclipses the C=C with a hydrogen but otherwise avoids the two C-H – C=C interactions. The difference between the two conformers is not trivial, about 2 kcal/mol. I think Ken Wiberg at Yale has looked into these calculations in some detail.

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