Determination of stereochemistry by spectroscopic methods

From time to time throughout the book we have spread before your eyes some wonderful structures. Some have been very large and complicated (such as palytoxin, p. 19) and some small but difficult to believe (such as tetra-f-butyl tetrahedrane, p. 373). They all have one thing in common. Their structures were determined by spectroscopic methods and everyone believes them to be true. Among the most important organic molecules today is Taxol, an anticancer compound from yew trees. Though it is a modern compound, in that chemists became interested in it only in the 1990s, its structure was actually determined in 1971. 

No one argued with this structure because it was determined by reliable spectroscopic methods— NMR plus an X-ray crystal structure of a derivative. This was not always the case. Go back another 25 years to 1946 and chemists argued about structures all the time. An undergraduate and an NMR spectrometer can solve in a few minutes structural problems that challenged teams of chemists for years half a century ago. In this chapter we will combine the knowledge presented systematically in Chapters 3,11, and 15, add your more recently acquired knowledge of stereochemistry (Chapters 16, 18, and 31), and show you how structures are actually determined in all their stereochemical detail using all the evidence available. 

It would be wise to review Chapter 18 now if what we said there is not fresh In your mind. 

The stereochemistry at two of the stereogenic centres of chlorocarolide was unknown when this structure was published—stereochemistry is one of the hardest aspects of structure to determine. Nonetheless, NMR is second only to X-ray in what it tells us of stereochemistry, and we shall look at what coupling constants (/ values) reveal about configuration, conformation, and reactivity. The first aspect we consider is the determination of conformation in six-membered rings. 

In the last chapter, we looked at some stereospecific eliminations to give double bonds, and you know that E2 elimination reactions occur best when there is an anti-periplanar arrangement between the proton and the leaving group, largest -Ufrom parallel orbitals 

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