Process intensification with biocatalysts: dynamic kinetic resolution and fluorous phase switch with continuous extraction

Abstract

Kinetic resolution of racemates with the help of enzymes has become a widely adopted method for the synthesis of chiral intermediates and compounds with biological activity. However, the inherent limitation to 50% yield of any one stereoisomer restricts the use of this method in industrial practice, when only one of the stereoisomers is required. The yield can theoretically be improved to 100% through either a chemical reaction, which inverts the stereochemistry at the optical active center, or through racemization of the unwanted isomer, followed by additional enzymatic resolution. The combination of the racemization of the slower reacting stereoisomer with kinetic resolution in a one-pot reaction is termed dynamic resolution. We describe the dynamic resolution of secondary alcohols through enzymatic stereoselective transesterification and heterogeneously catalyzed racemization of the alcohol over several zirconia-containing catalysts. In order to facilitate the separation of the products, we used a fluorous phase-switching technique coupled with fluorous extraction. The continuous extraction in a membrane contactor allows for facile recovery of the fluorous tagged species in a scaleable operation. The unoptimized scheme offers over 90% conversion with ca. 75% enantiomeric excess (e.e.).