A study on the origin of rate enhancement and enantiodifferentiation in the enantioselective hydrogenation of 2,2,2-trifluoroacetophenone (TFAP) over a Pt/alumina catalyst modified by cinchona alkaloids in toluene/acetic acid (AcOH) solvent mixture with and without trifluoroacetic acid (TFA) using continuous-flow fixed-bed reactor system is presented. The experimental data of the racemic - cinchona 1-cinchona 2-cinchona 1 hydrogenation series confirm the intrinsic nature of rate enhancement, namely the so-called "ligand acceleration" phenomenon. Hydrogenation in the presence of 0.1% (v/v) TFA follows the general rule of the Onto reaction, according to which the products formed in excess are (R)-alcohols on Pt-cinchonidine and Pt-quinine and (5)-alcohols on Pt-cinchonine and Pt-quinidine chiral catalysts. In toluene/AcOH mixture without TFA, unexpected inversion took place on the Pt-cinchonine and Pt-quinidine catalysts since the (R)-product formed in excess instead of the (S)-product. The observed unexpected inversion can be interpreted on the basis of the nucleophilic intermediate complex. Based on these observations we propose that in the hydrogenation of TFAP the reaction route involves the equilibrium of electrophilic and nucleophilic intermediate complexes, which was found to be dependent on the acid strength and concentration. (c) 2010 Elsevier B.V. All rights reserved.