Design of New Modifiers for the Enantioselective Hydrogenation of Ethyl Pyruvate

Abstract

All efficient chiral modifiers for Pt in the enantioselective hydrogenation of α-ketoesters possess a basic, secondary or tertiary N atom for interacting with the carbonyl group of the reactant and an aromatic ring system for adsorptive anchoring of the activated complex on Pt. Analysis of the available data suggested that an enlargement of the naphthalene or quinoline anchoring moiety should improve the enantioselection. Accordingly, 1-(9-anthracenyl)-2- (1-pyrrolidinyl)ethanol (10) has been synthesized and tested in the hydrogenation of ethyl pyruvate. The best enantiomeric excess achieved with the new modifier was 87%, which is 12% higher than the optimized value obtained with the corresponding naphthalene derivative (4). A further advantage of the new modifier is the higher stability against self-hydrogenation. Hydrogenation of ethyl pyruvate in the presence of modifier mixtures indicated the following order of adsorption strength on Pt: cinchonidine>10>4. This ranking correlates with the best enantiomeric excesses obtained with these modifiers. Compared with the other modifiers, the number of possible conformations for 10 is reduced because of the symmetry of the anthracenyl ring system. Molecular mechanics calculations suggest that the energy and geometry of the transition complexes between ethyl pyruvate and 10 or 4 are similar. Accordingly, the better efficiency of 10 should be due to its stronger adsorption on Pt and higher acceleration of the modified reaction compared with the competing nonenantioselective (unmodified) reaction. Substituting the 9-anthracenyl group of 10 with a 9-triptycenyl moiety led to a complete loss of enantiodifferentiation, demonstrating that the extendedflataromatic ring system is a crucial structural element of efficient modifiers for α-ketoester hydrogenation.