Catalyst development combinatorial approaches

We successfully developed combinatorial approaches for the discovery of industrial ligands and/or catalysts [Scheme l].1 Air-stable phosphine oxides with formal valence five in the presence of transition metals undergo tautomerization to the less stable phosphinous acids, which subsequently and... 

Maier, W. Kirsten, G. Orschel, M. WeiB, P.-A. Holzwarth, A. Klein, J., Combinatorial chemistry of materials, polymers, and catalysts, In Combinatorial Approaches to Materials Development, Malhotra, R., Ed. American Chemical Sodety Washington, DC, 2002 Vol. 814 1-21... 

Another synthetic area which has experienced the advantageous introduction of sol-gel encapsulation is that of combinatorial chemistry. The recently developed combinatorial approach to many complex synthetic efforts may benefit from sol-gel encapsulation in so-called one-pot reactions. Different reagents such as multiple catalysts may be encapsulated ( site-isolated ) in a sol-gel matrix, thereby offering the possibility of performing two or more successive or simultaneous reactions in a single vessel. One-pot synthesis may result in more sustainable synthetic routes as long as catalyst selectivity can be maintained at a level sufficient to allow good control over the succession of the different reactions [105]. 

This chapter will primarily cover combinatorial and parallel efforts to develop transition metal complexes as new catalysts. The considerable effort to use combinatorial approaches to make new inorganic materials will not be addressed (15-17). Additionally, the efforts to develop screens for combinatorial approaches to catalyst development will be addressed only in situations where they are used in the development of new catalysts. 

To date, the most frequently used ligand for combinatorial approaches to catalyst development have been imine-type ligands. From a synthetic point of view this is logical, since imines are readily accessible from the reaction of aldehydes with primary or secondary amines. Since there are large numbers of aldehydes and amines that are commercially available the synthesis of a variety of imine ligands with different electronic and steric properties is easily achieved. Additionally, catalysts based on imine ligands are useful in a number of different catalytic processes. Libraries of imine ligands have been used in catalysts of the Strecker reaction, the aza-Diels-Alder reaction, diethylzinc addition, epoxidation, carbene insertions, and alkene polymerizations. 

The last work pertaining to the discovery of new catalysts is perhaps the most novel approach to be reported thus far. In one of the earliest approaches taken toward catalyst development, Menger et al. (61) attempted to find catalysts for phosphate ester hydrolysis. A series of eight functionalized carboxylic acids were attached to polyallylamine in various combinations. Each of these polymers were then treated with one of three metals, Mg2+, Zn2+, or Fe3+. The different members of each library were identified by the relative percentages of each carboxylic acid attached to the polyamine. For example, one polymer possessed 15% Oct, 15% Imi, 15% Phe, and 5% Fe3+. There is no attempt to identify the location of the various carboxylic acids in a given polymer. This approach is novel since each system consists of an ensemble of different ligands with the carboxylic acids positioned in various locations. Each polymer within a given ratio of carboxylic acids consists of a combinatorial library of potential catalysts. 

The research described herein bears testimony to the fact that use of combinatorial protocols is becoming increasingly popular with researchers in the important field of chiral catalyst discovery. The majority of the above examples represent cases in which combinatorial approaches have led to the development of a new method in organic synthesis. There are numerous other disclosures involving optimization of established protocols that benefited from diversity-based approaches as well [23]. 

Combinatorial approaches to catalyst development with multichannel detectors... 

A very interesting solid phase combinatorial approach was developed by Jacobsen in 1998 for the identification and optimization of catalysts for the hydrocyana-... 

The peptide-based phosphine ligand 105 was identified from a polymer-supported phosphine library of 75 members [154]. Enantioposition-selective desymmetrization of the meso-cyclopentenediol derivative 100 was promoted by a palladium complex of 105 to afford the cyclic carbamate 101 with 76% ee. This result demonstrated that the combinatorial approach is effective in the lead-generation stage of stereoselective catalyst development [155, 156]. The resin-supported palladium complex of Ac-D-Phg-Pro-D-Val-Pps-D-Leu-NH resin 106, which has also been developed through the combinatorial approach. 

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