The New Clayden pp. 931 – 969

p. 935 — I don’t understand why neighboring group participation is less common using 4 membered rings than it is using  3 and 5 membered rings.  It may be entropy and the enthalpy of strain balancing out.  I think they’ve said this elsewhere (or in the previous edition).   Actually — looking at the side bar, they did say exactly that in Ch. 31.

As we used to say, when scooped in the literature — at least we were thinking well.

p. 935 — “During the 1950’s and 1960’s, this sort of question provoked a prolonged and acrimonious debate”  — you better believe it.  Schleyer worked on norbornane, but I don’t think he got into the dust up.  Sol Winstein (who Schleyer called solvolysis Sol) was one of the participants along with H. C. Brown (HydroBoration Brown).

p. 936 — The elegance of Cram’s work.  Reading math has changed the way I’m reading organic chemistry.  What you want in math is an understanding of what is being said, and subsequently an ability to reconstruct a given proof.  You don’t have to have the proof at the tip of your tongue ready to spew out, but you should be able to reconstruct it given a bit of time.   The hard thing is remembering the definitions of the elements of a proof precisely, because precise they are and quite arbitrary in order to make things work properly.  It’s why I always leave a blank page next to my notes on a proof — to contain the definitions I’ve usually forgotten (or not remembered precisely).

I also find it much easier to remember mathematical definitions if I write them out (as opposed to reading them as sentences) as logical statements.  This means using ==> for implies | for such that, upside down A for ‘for all’, backwards E for ‘there exists, etc. etc. There’s too much linguistic fog in my mind when I read them as English sentences.

So just knowing some general principles will be enough to reconstruct Cram’s elegant work described here.  There’s no point in trying to remember it exactly (although there used to be for me).   It think this is where beginning students get trapped — at first it seems that you can remember it all.  But then the inundation starts.  What should save them, is understanding and applying the principles, which are relatively few.  Again, this is similar to what happens in medicine — and why passing organic chemistry sets up the premed for this style of thinking.

p. 938 – In the example of the Payne rearrangement, why doesn’t OH attack the epoxide rather than deprotonating the primary alcohol (which is much less acidic than OH itself).

p. 955 – Although the orbitals in the explanation of why stereochemistry is retained in 1,2 migrations are called  molecular orbitals (e.g. HOMO, LUMO) they look awfully like atomic orbitals just forming localized bonds between two atoms to me.  In fact the whole notion of molecular orbital has disappeared in most of the explanations (except linguistically).  The notions of 50 years ago retain their explanatory power.

p. 956 — How did Eschenmoser ever think of the reaction bearing his name?  Did he stumble into it by accident?

p. 956 — The starting material for the synthesis of juvenile hormone looks nothing like it.  I suppose you could say its the disconnection approach writ large, but the authors don’t take the opportunity.   The use of fragmentation to control double bond stereochemistry is extremely clever.   This is really the first stuff in the book that I think I’d have had trouble coming up with.  The fragmentation syntheses at the end of the chapter are elegant and delicious.

On a more philosophical note, the use of stereochemistry and orbitals to make molecules is exactly what I mean by explanatory power.  Anti-syn periplanar is a very general concept, which I doubt was brought into being to explain the stereochemistry of fragmentation reactions (yet it does).  It appears over and over throughout the book in various guises.