Catalysts library, synthesis

A more detailed description of heterogeneous catalyst library synthesis (primary and secondary), primary screening, and secondary screening technologies is given in Chapter 3 and references therein. 

Cong, P., Doolen, R., Fan, Q. et al. (1999) High-throughput synthesis and screening of combinatorial heterogeneous catalyst libraries. Angew. Chem. Int. Ed., 38, 484. 

Kobayashi, S. Combinatorial Library Synthesis Using Polymer-supported Catalysts. In Combinatorial Chemistry, Fenniri, H., Ed., Oxford University Press Oxford, U.K., 2000 pp 421-432. 

When the peptide synthesis was complete, the phosphines were deprotected by sequential treatment with MeOTf and HMPT (Scheme 36.9). Addition of the rhodium precursor then created the catalyst library, which was screened, on the pin in the enantioselective hydrogenation of methyl-2-acetamidoacrylate (see Scheme 36.10). Unfortunately, this beautiful concept was poorly rewarded with rather low enantioselectivities. 

We have discussed the structure and synthesis of the library of molecular catalysts for polymerization in Section 11.5.1. In the present section we want to take a closer look at the performance of the catalyst library and discuss the results obtained [87], The entire catalyst library was screened in a parallel autoclave bench with exchangeable autoclave cups and stirrers so as to remove the bottleneck of the entire workflow. Ethylene was the polymerizable monomer that was introduced as a gas, the molecular catalyst was dissolved in toluene and activated by methylalumoxane (MAO), the metal to MAO ratio was 5000. All reactions were carried out at 50°C at a total pressure of 10 bar. The activity of the catalysts was determined by measuring the gas uptake during the reaction and the weight of the obtained polymer. Figure 11.40 gives an overview of the catalytic performance of the entire library of catalysts prepared. It can clearly be seen that different metals display different activities. The following order can be observed for the activity of the different metals Fe(III) > Fe(II) > Cr(II) > Co(II) > Ni(II) > Cr(III). Apparently iron catalysts are far more active than any of the other central metal... 

Kumaravel K, Vasuki G (2009) Four-component catalyst-free reaction in water combinatorial library synthesis of novel 2-amino-4-(5-hydroxy-3-methyl-lH-pyrazol-4-yl) H-chro-mene-3-carbonitrile derivatives. Green Chem 11 1945-1947... 

Here we present an alternative concept for optimizing homogeneous catalysts. Using a virtual synthesis platform, we assemble large catalyst libraries (lO -lO candidates) in silica, and use statistical models, molecular descriptors, and... 

In gas phase reactions the size of catalyst libraries can be over couple of thousands. For instance, in the synthesis of aniline by direct amination of benzene around 25000 samples were screened in about a year [15], however, the optimization method used was not discussed. In contrast, in liquid phase reactions taking place at elevated pressure and temperature, due to technical difficulties the rational approach does not allow testing libraries containing more than 200 250 catalysts. Consequently, the informatic platform and the strategy used to design catalyst libraries for high-pressure liquid phase reactions should have very unique optimization tools. 

However, with relevance to this review, Houpis et a/. " screened over 250 ligands and catalysts from the Lilly catalyst libraries (containing representatives from most commercial ligand families) under their standard conditions to synthesize the key intermediate for Naveghtazar synthesis. They obtained the best results (92% ee) employing WALPHOS as exemplified in Figure 1.13. 

For our microwave-promoted high-throughput library synthesis we decided to use a protocol that utilizes a combination of Lewis acids and Brpnsted acids as catalysts. 

There is still much debate as to whether synthetic operations should be divided into Stage I and Stage II operations. This is because synthetic operations at whatever scale they are performed should be scaleable and translate into the later technical application. It becomes clear from the above that the guideline for Stage II synthetic operations will in general be such that the unit operations employed for the material s synthesis will directly lead to scaleable synthetic operations that closely link to laboratory procedures and later the technical production. In extreme cases one may even employ catalyst libraries that stem completely from commercially produced materials to ensure straightforward production of a material in case it proves to be a hit. 

The design of a combinatorial catalyst library refers to the act of composing a sequence of synthesis steps such that the desired portion of a compositional or process parameter space will be mapped onto the final materials (catalyst) library. 

Serra et al. [122] used an evolutionary strategy for the design of catalyst libraries to evaluate a synthesis route for styrene from toluene. 

Rodemerck, U., Ignaszewski, P., Lucas, A., Claus, P., Parallel synthesis and fast catalytic testing of catalyst libraries for oxidation reactions, Chem. Eng. Technol. 

The advantages of heterogeneous solid phase in combinatorial chemistry, especially in terms of purification procedures, can be obtained also by solution-phase chemistry, using solid support assistance. The resin performs a specific function during the library synthesis and then is simply removed by filtration, leaving the pure library components in solution. A well-known adapted technique uses solid supported reagents or catalysts during a combinatorial synthesis, where the solid phase is filtered off and discarded after the reaction in which it was involved. A new application is represented by solid-phase purification, where one or more solid supports are added to trap the excess of... 

The use of solid supported, recyclable catalysts, is a well-assessed technique in classic organic chemistry, and many exhaustive reviews dealing with this subject are available [105, 115]. The use of solid supported catalysts for library synthesis in solution has also been reported. Among others, Kobayashi et al. presented the use of a new supported scandium catalyst for 3CC reactions leading to solution libraries of amino ketones, esters, and nitriles (24-member model discrete library) [116], or to quinolines (15-member model discrete library) [117], and Jang [118] presented a polymer bound Pd-catalyzed Suzuki coupling of organoboron compounds with halides and triflates. This area was also briefly reviewed recently [119]. 

Holzwarth et al. (51) reported the synthesis and IR thermographic-imaging screening of a 37-member, focused discrete heterogeneous catalyst library L6 for oxidations and reductions. The library was prepared using sol-gel solution synthetic protocols (47, 51) to produce the library individuals as amorphous microporous mixed oxides (AMMs), which have previously shown heterogeneous catalytic properties (54, 55). The scaffolding metal oxides contained either Ti (subset 1, Fig. 11.7) or Si (subset 2), and many active metal components were used. The complete structure of L6 is reported... 

Senkan and Ozturk (52) reported the synthesis and screening of a 66-member discrete heterogeneous catalyst library L7, containing Pt, Pd, and In, for the dehydrogenation of cyclohexane to benzene at 300 °C. The structure of L7 and its synthesis are reported in Fig. 11.8. Sixty-six jxrrous alumina pellets (30 mg each) were shaped into 0.3-cm-diameter, 0.1-cm-high cylinders (step a), then immersed in aqueous HCl solutions containing the 66 appropriate mixtures of InCh, PdCli, and HiPtCle (step... 

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