Synthetic modifiers for platinum in the enantioselective hydrogenation of ketopantolactone: A test for the mechanistic models of ketone hydrogenation

Various derivatives of (R)-1-(1-naphthyl)ethylamine have been synthesized and tested as chiral modifiers of Pt/alumina in the enantioselective hydrogenation of ketopantolactone. The best modifiers (ee up to 79%) possess an ester function in the alpha-position to the amino group. The modifiers performed far better in AcOH than in toluene, indicating that protonation of the N atom is important in enantioselection. The striking non-linear behaviour of modifier mixtures with cinchonine indicates that the alkaloid adsorbs much stronger on Pt than the naphthylethylamine derivatives. Two mechanistic models are proposed for interpretation of the results, involving an N-H-O or N+-H-O bond between the amine-type modifier and the keto carbonyl O atom of ketopantolactone, in apolar and protic media, respectively. In both cases the H atom originates from the modifier and not from the substrate ("half-hydrogenated-state"). The higher ee achieved in acidic medium is attributed to the better proton donor ability of the protonated amine modifiers. The models are applicable also to the hydrogenation of ethyl pyruvate.