Combinatorial chemistry solid support catalysts

One of the most exciting applications of this copper-mediated reaction is in solid-phase synthesis and combinatorial chemistry. Two approaches have been reported solid-supported catalyst and resin-supported substrates. 

The field of synthetic enzyme models encompasses attempts to prepare enzymelike functional macromolecules by chemical synthesis [30]. One particularly relevant approach to such enzyme mimics concerns dendrimers, which are treelike synthetic macromolecules with a globular shape similar to a folded protein, and useful in a range of applications including catalysis [31]. Peptide dendrimers, which, like proteins, are composed of amino acids, are particularly well suited as mimics for proteins and enzymes [32]. These dendrimers can be prepared using combinatorial chemistry methods on solid support [33], similar to those used in the context of catalyst and ligand discovery programs in chemistry [34]. Peptide dendrimers used multivalency effects at the dendrimer surface to trigger cooperativity between amino acids, as has been observed in various esterase enzyme models [35]. 

Immobilized catalysts on solid supports inherently have benefits because of their easy separation from the products and the possibility of recycling. They are also expected to be useful for combinatorial chemistry and high-throughput experimentation. The polystyrene-bound BINAP/DPEN-Ru complex (beads) in the presence of (CH3)3COK catalyzes the hydrogenation of l -acetonaphthone with an SCR of 12 300 in a 2-propanol-DMF mixture (1 1, v/v) to afford the chiral alcohol in 97% ee (Fig. 32.35) [113]. This supported complex is separable... 

Solid-phase synthesis is of importance in combinatorial chemistry. As already mentioned RuH2(PPh3)4 catalyst can be used as an alternative to the conventional Lewis acid or base catalyst. When one uses polymer-supported cyanoacetate 37, which can be readily obtained from the commercially available polystyrene Wang resin and cyanoacetic acid, the ruthenium-catalyzed Knoevenagel and Michael reactions can be performed successively [27]. The effectiveness of this reaction is demonstrated by the sequential four-component reaction on solid phase as shown in Scheme 11 [27]. The ruthenium-catalyzed condensation of 37 with propanal and subsequent addition of diethyl malonate and methyl vinyl ketone in TH F at 50 °C gave the adduct 40 diastereoselectively in 40 % yield (de= 90 10). 

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... 

Solid-phase supports used in combinatorial chemistry were used to prepare a cross-linked polystyrene bead containing a tetraethylene glycol spacer. The p-nitrosulfonate derivative of the polymer was substituted with NaCsHMesEt to form a supported cyclopentadiene, which was allowed to react with CpTiCls, making a tethered titanocene (Scheme 26). ° With MAO, this polymerizes ethylene with relatively low activity (41 g/mmol catalyst h) forming polymer with a noodle-like morphology. 

As early as 1984 Pd on graphite was reported as a catalyst in the alkylation of malonate diester " and few other examples of Pd in solid phases have followed.f f ° Anchoring the nucleophile to the solid support under conventional catalysis has been reported in connection with combinatorial chemistry. 

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