Conformational behavior of cinchonidine in different solvents:: A combined NMR and ab initio investigation

The conformation of cinchonidine in solution has been investigated by NMR techniques as well as theoretically. Three conformers of cinchonidine are shown to be substantially populated at room temperature, Closed(1), Closed(2), and Open(3), with the latter being the most stable in apolar solvents. The stability of the closed conformers relative to that of Open(3), however, increases with solvent polarity. In polar solvents the three conformers have similar energy. The relationship between relative energies and the dielectric constant of the solvent is not linear but resembles the form of an Onsager function. Ab initio and density functional reaction field calculations using cavity shapes determined by an isodensity surface are in good agreement with experiment for solvents which do not show strong specific interaction with cinchonidine. The role of the conformational behavior of cinchonidine is illustrated using the example of the platinum-catalyzed enantioselective hydrogenation of ketopantolactone in different solvents.