Is science sometimes in danger of getting tunnel vision? Recently published ebook author, Ian Miller, looks at other possible theories arising from data that we think we understand. Can looking problems in a different light give scientists a different perspective?

Alternative Theory For Synthetic Chemists

Chris Satterley raised a number of good points in his comment to my last blog, and I shall try to respond to some in the future, however the point I wish to discuss here is, is there a demand for new theory from synthetic chemistry?
I believe there is. When I commenced my PhD, there were a good number of "old" reactions available that a synthetic chemist might use, and the mechanisms of these were "understood"; the quotation marks is because while they were understood in general, I suspect there are still features that require looking into. Since then, however, there have been a bewildering number of new reactions, and these appear to be discovered at quite an alarming rate (unless you are a synthetic chemist that reads about something that unblocks a problem!). I believe that the main difficulty in rationalizing these reactions is that without the salient aspects being identified and ordered by the synthetic chemists, nobody has sufficient information. The problem, in my opinion, is that because the information is so dispersed, and more importantly, will be scattered across a number of specialties, nobody can get at more than a minute fraction of it.
Let me provide an example of what I mean. What I regard as a rather impressive synthetic method recently appeared in JACS 133: 9724-9726, in which indium bromide, or better, indium iodide, was used as a catalyst to condense chiral propargylic alcohols into polycyclic products with high yield and stereoselectivity. Now, the question is, why pick on indium iodide? Would that be one of your picks, if you hadn't read that paper? One of the authors was E. J. Corey, and I am ready to take a bet that he did not go through the store picking on random catalysts. When he wrote "we speculated that . ." I believe his reasoning would be a lot better than that.  What he wrote as a reason was the indium salt might, by virtue of its vacant 5s and 5 p orbitals coordinate with the acetylenic unit through its pi(x) and pi(y) orbitals while also coordinating with the propargylic oxygen. The reason indium was selected was because the s and p orbital energies are closer than, say, aluminium.
 I suspect there is more to it than that. There is no doubt whatsoever that Professor Corey has an incredible knowledge of organic synthesis, and I believe it would also be interesting to know why he focussed on indium. There is little doubt that he recognized that some form of Lewis acid would be desirable, and I would expect that some other possible salts, including indium chloride, might be rejected on solubility grounds.
To me, the reasoning he gives leaves a number of puzzling thoughts. Superficially, he appears to be specifying empty sp2 orbitals, although maybe he is not. However, if so, and if we consider the electrons to have wave characteristics to their motion, there appear to be some strange refractive issues, although since we do not know the configuration he was considering, that may not apply. But even if we put that aside, if Professor Corey's reasoning is correct, surely thallium could possibly be better (if closeness of orbital energies is relevant) or possibly gallium (if Lagrangian density in the orbital is relevant) but while some other elements were mentioned, including silver and gold, these two did not appear to be mentioned. (There is an implication that some further possible catalysts were tried, but were unsuccessful, and these failures were not identified. This is unfortunate, because the failures are also important from a theoretical point of view.) Of course the paper is one describing a synthetic method, and what I am discussing was presumably outside Professor Corey's interest (and no criticism is implied for that). The only point I am trying to make is to address Chris' point: there are theoretical aspects involved in such synthetic methods which, if unravelled explicitly, might permit more general progress to be made in synthetic chemistry, and would certainly help other chemists who have to carry out syntheses to make materials for reasons other than simply specifying synthetic methods.
Posted by Ian Miller on Jul 2, 2011 5:00 AM Europe/London

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