Bridged bicyclic molecule NMR challenge

As the name implies, a bicyclic molecule contains two joined rings. Bridged bicyclic structures occur widely in many biologically important natural molecules such as borneol and camphor. Indeed, such molecules are object of high interest in organic chemistry and drug discovery owing to their attractive pharmacokinetic properties.

A common challenge for NMR scientists concerning bridged bicyclic molecules is the determination of the relative orientation of substituents in such molecules, as shown in Fig. 1.

The standard and likely the most convenient approach to NMR structure elucidation of such substances is the NOESY experiment to observe NOE correlations of protons neighboring the substituent group R with the protons of the nearby CH₂ groups belonging to either the short bridge (for endo isomer) or the long bridge (for exo isomer) of the bicycle.

But there is often a simpler way for the structure elucidation of such molecules, especially if the short bridge contains a heteroatom. In such cases, the spin-coupling picture of the protons located at the bridgehead positions becomes simpler.