Enantioselective Hydrogenation: III. Methyl Pyruvate Hydrogenation Catalyzed by Alkaloid-Modified Iridium

Abstract

Enantioselective hydrogenation of methyl pyruvate, MeCOCOOMe to methyl lactate, MeCH(OH)COOMe, is catalyzed in solution at room temperature by supported iridium catalysts modified with cinchona alkaloids. Modification with cinchonidine or quinine yields R-lactate in excess, whereas modification with cinchonine or quinidine favors S-lactate formation. Ir/SiO 2 catalysts (20%) calcined at 393 to 573 K and reduced at 523 to 593 K were highly active for racemic hydrogenation in the absence of a modifier (rates typically 1.8 mol h −1 g −1 cat) and were comparably active when modified with cinchonidine but gave an enantiomeric excess of about 30%. Use of higher calcination or reduction temperatures led to substantially inferior activity and selectivity. The high rates recorded for both racemic and enantioselective reactions are dependent on the catalysts being activated before use by a procedure involving exposure of the catalyst to air after the initial reduction. Use of a Cl-free precursor gave an Ir/SiO 2 catalyst (20%) of superior activity but inferior enantioselectivity. Ir/CaCO 3 (5%) was more active for racemic hydrogenation than for enantioselective hydrogenation, but provided the highest value of the enantiomeric excess 39%. Kinetics of reaction are reported. Exchange of H for D in 10,11-dihydrocinchonidine at room temperature over Ir/CaCO 3 occurred in the quinoline moiety but not in the quinuclidine ring system, indicating that the alkaloid was adsorbed to the Ir surface via the interaction of its π-electron system. For both silica-supported and calcium carbonate-supported Ir, the presence of chloride ion in the catalyst was advantageous for the achievement of enantioselectivity.