Design and synthesis of a heterogeneous asymmetric catalyst

Abstract

The need for enantiomerically pure pharmaceuticals and insecticides drives the search for new catalysts that can perform asymmetric reactions with high enantiomeric selectivity. Many chiral transformations are accomplished using homogeneous catalysts. Recently we reported a heterogeneous catalyst for asymmetric hydrogenation reactions, in which an organometallic catalytic complex is held in a film of water on a porous hydrophilic support, while the reactants and products remain within a hydrophobic organic phase. Such systems provide a large interfacial area between the catalytic phase and the solvent, and should facilitate the separation of product from catalyst. Our previous system gave selectivities of only about 70% enantiomeric excess, however, whereas values of at least 95% are needed for practical utility. Here we describe a modified process in which an enantiomeric excess of 96% is obtained for the asymmetric reduction of 2-(6′-methoxy-2′-naphthyl)acrylic acid to the commercially important anti-inflammatory agent naproxen. We use ethylene glycol as the hydrophilic liquid phase containing the chiral catalyst, which effectively prevents the leaching of the complex into the organic phase. Our results show that these supported-phase asymmetric catalytic systems have the potential to become commercially viable.