ASYMMETRIC-SYNTHESIS OF NAPROXEN BY SUPPORTED AQUEOUS-PHASE CATALYSIS

A supported aqueous-phase, asymmetric, hydrogenation catalyst, SAP-Ru- BINAP-4SO3Na, is synthesized. Impregnation of water from an organic ph ase, ethyl acetate, is used to hydrate the SAP catalyst. Both the acti vity and enantioselectivity for the asymmetric hydrogenation of 2-(6'- methoxy-2'-naphthyl)acrylic acid to naproxen are found to be dependent on the water content. Maximum activity and e.e. are observed when wat er-saturated ethyl acetate is used to hydrate the SAP catalyst, an ini tial turnover frequency of 18.2 hr-1 and a 70.0% e.e. at room temperat ure under approximately 1350 psig of hydrogen pressure. At similar con ditions, initial turnover frequencies of 131 and 0.34 hr-1 are observe d from Ru-BINAP-4SO3Na in homogeneous (methanol as solvent) and two-ph ase (water-ethyl acetate) reaction systems, respectively. Although an excellent 96. 1 % e. e. (at 4-degrees-C and 1230 psig of H-2) iS found in neat methanol (homogeneous), the enantioselectivity of the SAP cat alyst (up to 70% e.e.) is bounded by the intrinsic enantioselectivity limit of the ruthenium complex in water. Recycling of the SAP catalyst is easily achieved without any leaching of ruthenium into the organic phase. (C) 1994 Academic Press, Inc.