The enantioselective hydrogenation of 2,2,2-trifluoroacetophenone (1) on cinchona-modified Pt, combined with the diastereoselective hydrogenation of cinchonidine and NMR analysis of the modifier-substrate-product interactions, revealed the key role of the product (S)-1-phenyl-2,2,2-trifluoroethanol (2) in enantioselection. We propose a multiple cycle mechanism including a racemic route (a) on the unmodified sites and three enantioselective routes. In the enantioselective cycles, there is an N-H-O type interaction between the quinuclidine N and the carbonyl O-atom of the substrate. At low conversion, the alkaloid alone is the source of chiral information (route b). With increasing conversion, the weakly acidic minor product (S)-2 forms an adduct with the alkaloid and this complex controls the enantioselection (route c, lower ee). The frequently applied strong acid additive TFA replaces (S)-2 and the alkaloid-TFA complex gives the highest ee (route d). The diastereoselective hydrogenation of cinchonidine disproves a former mechanistic model proposed in the literature. (C) 2011 Elsevier Inc. All rights reserved.