DESIGN OF NEW MODIFIERS FOR THE ENANTIOSELECTIVE HYDROGENATION OF ETHYL PYRUVATE

All efficient chiral modifiers for Pt in the enantioselective hydrogen ation of alpha-ketoesters possess a basic, secondary or tertiary N ato m for interacting with the carbonyl group of the reactant and an aroma tic ring system for adsorptive anchoring of the activated complex on P t. Analysis of the available data suggested that an enlargement of the naphthalene or quinoline anchoring moiety should improve the enantios election. Accordingly, 1-(9-anthracenyl)-2-(1-pyrrolidinyl)ethanol (10 ) has been synthesized and tested in the hydrogenation of ethyl pyruva te. The best enantiomeric excess achieved with the new modifier was 87 %, which is 12% higher than the optimized value obtained with the corr esponding naphthalene derivative (4). A further advantage of the new m odifier is the higher stability against self-hydrogenation. Hydrogenat ion of ethyl pyruvate in the presence of modifier mixtures indicated t he 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 o f 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 accele ration of the modified reaction compared with the competing nonenantio selective (unmodified) reaction. Substituting the 9-anthracenyl group of 10 with a 9-triptycenyl moiety led to a complete loss of enantiodif ferentiation, demonstrating that the extended flat aromatic ring syste m is a crucial structural element of efficient modifiers for alpha-ket oester hydrogenation. (C) 1998 Academic Press.