The influence of acetic acid (AcOH) and trifluoroacetic acid (TFA) on the hydrogenation of ethyl-4,4,4-trifluoroacetoacetate has been investigated by using Pt/Al₂O₃ modified by cinchonidine and O-methylcinchonidine. We have shown that the sometimes dramatic changes in enantioselectivity and rate cannot simply be interpreted by protonation of the alkaloid modifier. We propose a new three-step reaction pathway, involving interaction of the carboxylic acid with the reactant and the chiral modifier. The mechanism is supported by IR spectroscopic identification of cyclic TFA–modifier ion pairs. This new approach can rationalise the poorly understood role of acids in the enantioselective hydrogenation of activated ketones over cinchona-modified platinum metals.

The relation between the electronic structure of α-substituted ketones and their reactivity in the racemic and enantioselective platinum-catalyzed hydrogenation has been investigated using a combined theoretical and experimental approach. A correlation between the keto carbonyl orbital energy and the hydrogenation rate has been found, which rationalizes the effect of the substituent on the rate of hydrogenation. The uncovered relationship between the keto carbonyl orbital energy and the hydrogenation rate provides a rational explanation for the often observed rate acceleration that occurs when cinchona-modified platinum is used as a enantioselective hydrogenation catalyst. The previously suggested model for enantiodiscrimination based on the different stability of the diastereomeric complexes formed between the reactant and the cinchona modifier is discussed in the light of the new kinetic findings.