Catalyst Development, Screening and Optimization

Early on in the development of new organometallic (catalytic) reactions, the isolation and characterization of metal complexes participating in the reaction is often key, as screening and optimization implicitly rely on structure-property relationships. While catalyst precursors are by necessity stable and thus relatively easy to characterize with a variety of spectroscopic (most commonly perhaps infrared (IR), nuclear magnetic resonance (NMR), and ultraviolet/visible (UV-Vis)) and (X-ray) diffraction techniques, the catalytically active/relevant intermediates may only be transient. Nevertheless, careful kinetic measurements to determine the relationships between the concentrations of individual reagents... 

The last two decades have seen enormous developments in catalyst discovery and optimization tools, notably in the area of high-throughput experimentation (HTE) and process optimization (5). However, the basic concept used for exploring the catalyst space in homogeneous catalysis has not changed Once an active catalyst complex is discovered, small modifications are made on the structure to try and screen the activity of neighboring complexes, covering the space much like an ink drop spreads on a sheet of paper. This is not a bad method, but can we do better with the new tools that are available today ... 

With the above considerations in mind, in the past five years, we have prepared and examined numerous chiral Mo-based catalysts for both asymmetric RCM (ARCM) and ROM (AROM) transformations [5]. In this article, we highlight several efficient and enantiose-lective reactions that are catalyzed by these chiral complexes [6], The structural modularity inherent to the Mo-based systems allows screening of catalyst pools, so that optimal reactivity and selectivity levels are identified expeditiously. Initial advances towards the development of chiral Ru-based metathesis catalysts are also discussed. 

The utility of the traditional approach to asymmetric catalysis, involving synthesis and screening of chiral ligands and complexes in catalytic reactions is a powerfiil method for the development and optimization of catalytic asymmetric processes. Such an approach, however, can be cumbersome if the ligands are difficult to synthesize and modify. In these cases, alternative strategies to the generation of asymmetric catalysts provide access to a large number of catalysts with minimal effort. The remainder of this section will focus on these methods. 

B.V., Catalysts and Chemical Division, PO Box 19, 3454 ZG De Meern, The Netherlands Heraeus, Chemical Catalysts, Postfach 1553, D-63450 Hanau 1, Germany Johnson Matthey, Process Catalysts, Orchard Road, Royston, Hertfordshire SG8 5HE, UK. They also have a substantial know-how about which type of catalyst is the most suitable for a specific problem. Our experience has shown that it is of advantage to search for or optimize a suitable catalyst in close collaboration with the catalyst suppliers. This is especially true for the development of technical processes and/or when the development team has little hydrogenation experience. Catalyst screening and development should always be performed with specified catalysts that can be supplied in technical quantities when needed. For laboratory use, Fluka and Aldrich Inorganics offer a wide variety of hydrogenation catalysts that are adequately suited for preparative purposes, although the catalyst manufacturer and the exact type of catalyst is not usually specified. 

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