ABSTRACT
Jason P. Hallett, Pamela Pollet, Charles A. Eckert and Charles L. Liotta
School of Chemistry and Biochemistry School of Chemical & Biomolecular Engineering
Specialty Separations Center Georgia Institute of Technology
Atlanta, GA 30332-0325
charles.liotta@carnegie.gatech.edu Abstract Homogeneous catalysts possess many advantages over heterogeneous catalysts, such as higher activities and selectivities. However, recovery of homogeneous catalysts is often complicated by difficulties in separating these complexes from the reaction products. The expense of these catalysts (particularly asymmetric catalysts) makes their recovery and re-use imperative. We have developed several techniques using CO2 as a “miscibility switch” to turn homogeneity “on” and “off”. The goal is to create a medium for performing homogeneous reactions while maintaining the facile separation of a heterogeneous system. Our approach represents an interdisciplinary effort aimed at designing solvent and catalytic systems whereby a reversible stimulus induces a phase change enabling easy recover of homogeneous catalysts. The purpose is to preserve the high activity of homogeneous catalysts while taking advantage of simple separation techniques, such as filtering and extraction, normally applied to heterogeneous or biphasic catalytic systems. Specific examples include the application of gaseous CO2 as a benign agent in gas-expanded liquids to induce organometallic catalytic recycle of water/organic, fluorous/organic biphasic systems. Additional applications involve the enhancement of solid-liquid phase transfer catalysis with supercritical solvents and improved recovery of phase transfer catalysts from biphasic liquid mixtures using gas-expanded liquids. Specific reaction systems include the hydroformylation of hydrophobic olefins using water-soluble catalysts, the hydrogenation of pro-chiral and achiral substrates using fluorous-modified catalysts captured in a fluorinated solvent or on a fluorous surface phase, the hydrolysis of hydrophobic esters using enzymatic biocatalysts in mixed aqueous/organic media, and nucleophilic substitutions using novel phase transfer catalyzed systems. Introduction Catalytic synthesis can be achieved by a variety of methods, including homogeneous and heterogeneous organometallic complexes, homogeneous enzymatic biocatalysts, phase transfer catalysts, and acid and base catalysts. However, each of these
methods offers advantages and disadvantages that must be balanced cautiously. Homogeneously catalyzed reactions are highly efficient in terms of selectivity (i.e. regioselectivity, enantiomeric excesses) and reaction rates, due to their monomolecular nature. Unfortunately, catalyst recovery can be very difficult (due to the homogeneous nature of the solution) and product contamination by residual catalyst or metal species is a problem. In contrast, heterogeneously catalyzed reactions allow easy and efficient separation of high value products from the catalyst and metal derivatives. However, selectivity and rates are often limited by the multiphasic nature of this system and/or variations in active site distribution from the catalyst preparation. Catalyst separation is crucial for industrial processes – to minimize the waste streams and to develop potential catalyst recycling strategies. Therefore, efforts have been made to improve the recovery of highly selective homogeneous catalysts by developing new multiphasic solvent systems. We have developed several techniques using CO2-expanded liquids and supercritical fluids to create a medium for performing homogeneous reactions while maintaining the facile separation of heterogeneous systems. Results and Discussion One example of a recoverable homogeneous catalytic system involves the addition of CO2 to fluorous biphasic systems (1,2). In fluorous biphasic systems, a fluorous solvent (perfluoroalkane, perfluoroether or perfluoroamine) is employed as an orthogonal phase, immiscible with most common organic solvents and water. An organometallic catalyst can be made preferentially soluble in a fluorous solvent by introduction of one or more fluorous side chains, or “ponytails” (3) with hydrocarbon spacers (4) to mitigate the electron-withdrawing effects of the fluorines. Usually, multiple ponytails are required to impart preferential solubility to most organometallic complexes (5). The mutual immiscibility of fluorous and organic solvents (6) provides an opportunity for facile separation of reaction components and the recycle of the expensive fluorous-derivatized homogeneous catalyst. However, mass transfer limitations in biphasic systems can limit overall reaction rate. In systems containing nonpolar solvents, such as toluene, heating the biphasic reaction mixture to around 90°C will induce miscibility (3). However for more polar or thermally labile substrates this is not a viable option as the consulate point is much higher than 100 °C (7,8). Thus, any polar reactants must be diluted into a nonpolar solvent, introducing an extra volatile organic compound into the process. Instead of heating, a homogenizing agent such as benzotrifluoride (BTF, 9) can be added to mixture. However, BTF is expensive and its recovery is not trivial.
