Quaternary ammonium derivatives of cinchonidine as new chiral modifiers for platinum

The mechanistic models developed for the enantioselective hydrogenation of ethyl pyruvate are based on the fundamental observation that transformation of the basic quinuclidine N atom of cinchonidine to quaternary cinchonidinium salts results in the complete loss of enantioselectivity. Astonishingly, the N-methyl, N-benzyl, and N,O-dimethyl derivatives of cinchonidine are effective chiral modifiers of Pt in the hydrogenation of a cyclic α-ketoester, ketopantolactone. All three alkaloid derivatives gave (S)-pantolactone in excess, the configuration that is the opposite of that provided by cinchonidine, O-methyl cinchonidine, and cinchonidinium hydrochloride. Under mild conditions at 3 bar, Pt/Al2O3 modified by N,O-dimethyl-cinchonidinium chloride afforded 44.5% ee, which is comparable to the performance of cinchonidine (51.5% ee). A mechanistic model is proposed that is based on an electrostatic interaction between the cinchonidinium cation and the free electrons of the keto group of the reactant. The observations highlight the importance of the structural rigidity of the reactant in the enantioselection and the frequently reported substrate specificity of chirally modified Pt. Under certain conditions (dichloromethane, N,O-dimethyl-cinchonidinium chloride as modifier), doubling of the ee with conversion was observed. The reason for this phenomenon could not be clarified, but it may be due to some restructuring of the nanoparticle surfaces on the atomic scale.