Beware of Rationalization

It has been almost a year since the start of this blog.  In this, the one hundredth, post I want to draw attention to one of the things I encountered during my sabbatical and its bigger picture lessons which don't fit neatly into the paper I am working on.  I won’t go into the specifics as I am working on the paper and my point here is bigger picture than this specific case, however illustrative.

The research I have engaged in involves a stereoselective condensation reaction to form a heterocycle.  A number of years ago the major player in the field proposed a mechanism for the condensation as a rationalization of the observed stereochemistry in one of their papers.  That mechanism has since been used, or more commonly the proposed stereo-setting transition state geometry has used, by many others to rationalize observed stereochemistry in this type of heterocycle formation.   The systems to which the mechanism has been applied have become increasingly complex and people have generally added groups onto the original transition state structure without revisiting the mechanism itself.  

In our study we found that the proposed transition state geometry not only fails to predict the major isomers observed but also predicts that our major product isomer can not be formed.  This made me reconsider a number of the prior studies.  It appears that the transition state of the rationalized mechanism was applied by many without considering other transition states in that original mechanism, or other mechanisms.  When I looked at the other transitions states available in the original mechanism in the more complex systems it was clear that the energy differences of the various transitions states don't justify the observed stereoselectivity.  Over the last two decades authors appear to have never gone back to the point of considering all the possible transition states, or to reconsidering the mechanism in the face of additional data and systems.  For my part I am proposing a different mechanism for the reaction.  Of course this is the nature of the scientific method in practice.  

The author of the original mechanism did not suggest that the mechanism was more than a rationalization to explain the observed stereochemisty.  The point of this story in the context of today's blog is that while the original rationalization was reasonable in the context of the original work, the practice of assuming that it was correct as the system became more complex passed muster with authors and reviewers over the past twenty odd years.  People have made their names on this work and earned major awards.  No-one appears to ever have asked if the original rationalized mechanism still held in the face of additional data.  The rationalization became dogma for reasons that may have more to do with lethargy and bowing to authority (the name of the author of the original mechanism) than because the scientific method was applied.  The original author did no in depth study to support the proposal.  It was only a rationalization, yet over the last couple of decades it has become so much more.  As research scientist and educators we must question what we believe and ask ourselves if we believe because it is dogma and to do otherwise is to blaspheme, or if on reconsideration in light of all currently available data we should revise some of the base assumptions of our field.

T.S. Hall