Catalyst library

The reaction was first tested with these substances as ligands but the organic molecule, in the absence of any added metal ion, proved to be the most enantioselective catalyst (library 1 19% ee vs. less than 13% ee for the best metal catalyst). The effects of selective variations of the amino acid nature and of the salicylidene moiety on the diamine structure were investigated for urea and thiourea derivatives via HTS (library 2 48 urea compounds and... 

Snively, C.M., Oskarsdottir, G. and Lauterbach, J. (2001) Parallel analysis of the reaction products from combinatorial catalyst libraries. Angew. Chem. Int. Ed., 40, 3028. 

Senkan, S., Krantz, K., Ozturk, S. et al. (1999) High-throughput testing of heterogeneous catalyst libraries using array microreactors and mass spectrometry. Angew. Chem. Int. Ed., 38, 2794. 

Senkan, S.M. (1998) High-throughput screening of solid-state catalyst libraries. Nature, 394, 350. 

A given ligand system was first prepared on the solid support, and a small collection of catalysts (library 1) generated by adding 11 different metals and in one case no metal (Scheme 23).119 It turned out that the best ee-value (19%) was in fact obtained in the metal-free system. Based on this... 

Thirteen different chiral diol ligands were used (Scheme 25), leading to a catalyst library of 104 members.121 In a model reaction benzaldehyde (51), (R = Ph) was used as the carbonyl component, HPLC being used to ascertain the enantiopurity of (92). Initially 1 mol.% of catalyst was used. In the primary screening catalysts modified by L4, L5, L6, and L7 turned out to be excellent (77-96% ee yields 63-100%). Thereafter the catalyst loading of Lm/Ti/Lra (m, n = A-l) was decreased to 0.1 mol.%, but this led to only trace amounts of product. Finally, the solvent was... 

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... 

The asymmetric hetero-Diels-Alder reaction of aldehydes with Danishefsky s diene catalyzed by Ti catalysts generated from a library of 13 chiral ligands or activators has also been reported (Scheme 8.18). The catalyst library contains 104 members. The Ti catalysts bearing L, L , L, and J are found to have a remarkable effect on both enantioselectivity (76.7-95.7% ee) and yield (63-100%). On the other hand, ligands bearing sterically demanding substituents at the 3,3 -positions are found to be detrimental to the reaction. The optimized catalysts, both L /Ti/L and L /Ti/L , are the most efficient for the reaction of a variety of aldehydes, including aromatic, olefinic, and aliphatic derivatives. 

Figure 6.11 Typical tridentate ligand structure incorporating a chiral amino alcohol and modified diamine-based tridentate ligand structure attached to the solid support for parallel catalyst library strategy.

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... 

A full discussion of all the issues related to this concept is out of the scope of this preliminary communication. Instead, we present here the basics of the general approach, as well as a specific example illustrating one iteration in the optimization of Pd-catalyzed Heck reactions using bidentate ligands, which demonstrate higher catalytic activities and lifetimes than monodentates (6). The full technical details of the algorithms and the theoretical treatment of the catalyst library diversity will be published elsewhere (7). 

Catalyst Library Design for Fine Cnemistry Applications... 

The methods used for catalyst library design are quite divers. Industrial companies, like Symix, Avantium, hte GmbH, Bayer AG are using their own proprietary methods. In academic research the Genetic Algorithm (GA) is widely applied [11,12]. Recently Artificial Neural Networks (ANNs) and its combination with GA has been reported [13,14]. In these studies ANNs have been used for the establishment of composition-activity relationships. 

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. 

The lack of the use of catalyst library design tools in the field of heterogeneous catalytic hydrogenation inspired us to describe our approach used in this area. In this presentation we shall depict our complex approach to design, optimize and mapping catalyst libraries. 

The design and optimization of a catalyst library for selective hydrogenation is based on the knowledge accumulated in the patent and open literature. In this study we shall focus on catalysts libraries related to supported metals. The catalyst library optimization is performed in an iterative way. First a rough experimental space is created, tested and optimized by HRS. 

Catalyst library design is considered as an optimization procedure in a multidimensional experimental space. The variables in the multi-dimensional space can be differentiated as follows (i) compositional variables, and (ii) process variables. The term compositional variables have already been discussed. 

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