Anomalous behavior of rigid cinchona alkaloids in the enantioselective hydrogenation of ethyl pyruvate in an aprotic solvent Original Research Article

The enantio-differentiation (ED) ability of rigid cinchona alkaloids, such as α- and β-isocinchonines (α-ICN, β-ICN), was investigated in the asymmetric hydrogenation of ethyl pyruvate (EtPy) in toluene at low modifier (M) concentration ([M]0 = 1.2 × 10−5 M). The isocinchonines showed anomalous kinetic behavior, i.e., lack of rate acceleration (α-ICN), low ee values, monotonic decrease-type ee - conversion dependencies, independence of the ee on modifier concentration and reaction temperature. When α-ICN was co-injected with either cinchonidine (CD) or cinchonine (CN) the ee-conversion dependencies observed in the presence of pure CD or CN were not altered. The new results indicate that in aprotic solvent the ED ability of flexible and rigid cinchona alkaloids, such as CD, CN and α-ICN, β-ICN should have different origin. It is suggested that ED can take place either in the liquid phase (CD, CN, β-ICN) or at the Pt surface (α-ICN). The formation of substrate–modifier complex in the liquid phase furnishes pronounced rate acceleration for cinchonidine (CD), cinchonine (CN) and β-ICN, but high ee values were obtained only for CD and CN. However, interactions taking place at the Pt surface (α-ICN) result in low ee values and no rate acceleration. Results presented in this study show that both α-ICN and β-ICN only partly resemble the properties of CD or CN, the flexible alkaloids. No RA was also observed when other rigid modifiers, such as (−)-sparteine and (+)-dihydrovinpocetine, were used. These modifiers show similar kinetic patterns as α-ICN.