Molecular interaction between cinchonidine and acetic acid studied by NMR,FTIR and ab initio methods

Cinchona alkaloids play a major role as chiral auxiliaries in asymmetric ca talysis. Acetic acid is known to be an excellent solvent in the enantiosele ctive hydrogenation over chirally modified platinum metals. The crucial int eraction between the chiral auxiliary and the solvent has been investigated using the cinchonidine-acetic acid pair. Solutions containing cinchonidine and acetic acid were studied by means of NMR and IR spectroscopy as well a s by ab initio Hartree-Fock calculations. In the presence of the acid cinch onidine is protonated at the quinuclidine N and adopts an open conformation where the quinuclidine N points away from the quinoline moiety. In the mos t stable 1 :1 and 2: I acetic acid-cinchonidine complexes both the N-H+ and O-H groups of cinchonidine are involved in hydrogen bonding. The most stab le 1 : 1 complex is found to be cyclic. The relative arrangement of the N-H + and O-H groups of protonated cinchonidine is ideally suited to bind an ac etate anion, and the interaction hardly affects the cinchonidine conformati on. Several 2: 1 acid-base complexes coexist in solution. The IR spectra gi ve evidence for the existence of a 2: 1 cyclic complex. Calculated structur es, relative energies and vibrational frequencies are in good agreement wit h the experiment. The findings rationalise the importance of the O-H group of cinchonidine for the enantiodifferentiation in the enantioselective hydr ogenation of alpha,beta-unsaturated carboxylic acids over cinchonidine-modi fied Pd.