Inversion of enantio selectivity in the hydrogenation of ketopantolactone on a Pt-β-ICN chiral catalyst

The enantioselective hydrogenation of ketopantolactone (KPL) both in AcOH and in toluene was studied oil a Pt-alumina catalyst modified by alpha-isocinchonine (alpha-ICN) and beta-isocinchonine (beta-ICN). The effects of the modifier concentration, temperature, solvents, and mixtures of modifiers on the reaction rate and enantioselectivity were examined under illild experimental conditions (253-298 K, 1 bar H-2 pressure, 0.001-0.1 mM/L modifier concentration). Formation of excess (S)-PL was observed in the presence of alpha-ICN in both solvents (ee(max) 37%). In the enantioselective hydrogenation of KPL over a Pt-alumina-beta-ICN chiral catalyst, the major enantiomer was (R)-PL (eemax, 60%) in toluene, whereas in AcOH, (S)-PL (ee, 5%) was formed. The (R) configuration was opposite to what was expected from the absolute configuration of the cinchonine backbone; namely, inversion of enantioselectivity occurred. The conformational rigidity of both chiral modifier and reactant provides new insight into the possible structure of intermediate complexes in the enantioselective hydrogenation of activated ketones. The proposed structure of the intermediate responsible for the inversion of enantioselectivity is all adsorbed 1: 1 beta-ICN-KPL surface complex [C1 pro(R) and C2 pro(R)] in which the beta-ICN acts as a nucleophile and binds KPL. (c) 2006 Elsevier Inc. All rights reserved.