Soluble supports dendrimers

A prerequisite for the application of filtration methods is a significant difference in molecular size of the catalyst and the reactants / products. Molecular enlargement, i.e. binding the homogeneous catalyst to soluble supports, is often the method of choice. These supports can be dendrimers, hyper-branched polymers or even simple polymers, giving the opportunity to tailor the support according to the given process. 

A stochiometric approach was applied by Van Koten and co-workers [29], who used chiral carbosilane dendrimers as soluble supports in the in situ ester enolate-imine condensation in the synthesis of /Mactams (e.g. 19, Scheme 20). The formation of the /Mactam products proceeded with high trans selectivity, and with the same level of stereoinduction as was earlier established in reactions without the dendritic supports, (i.e. the use of the enantiopure dendritic support did not affect the enantioselectivity of the C-C bond formation). After the reaction, the dendrimer species could be separated from the product by precipitation or GPC techniques and reused again. 

In 1996, Kim and coworkers reported for the first time on the use of a polyami-doamine (PAMAM) dendrimer [Gl] as a soluble support for organic synthesis (Fig. 7.5) [37]. Advantages of PAMAM are its commercial availability and its high symmetry, which provides uniform site accessibility (in lower generations) and facilitates NMR interpretation. By attaching 4-hydroxymethylbenzoic acid (HMB) to... 

Dendrimers, among other applications, are generating interest as soluble supports thanks to the following intrinsic characteristics (i) the well-defined molecular composition of a dendrimer provides a support with a precisely defined arrangement of the reactive sites, (ii) a high loading of reactive sites is achieved on the dendrimer surface and (iii) nanofiltration techniques are available to separate the dendritic support from products. Dendrimer 143, based on a carbosilane core, possesses 12 ester functionalities on... 

A related approach, termed dendrimer-supported combinatorial chemistry (DCC), has been disclosed by Kim et al. [23], It uses dendrimers as soluble supports (see Fig. 7). In this case the reactions are performed in solution and the dendrimeric intermediates are isolated/purified by size exclusion chromatography. The strategy was validated by the preparation of a 3 x 3 x 3 combinatorial library using the Fischer indole synthesis. 

The use of dendrimers as soluble supports in combinatorial chemistry was recently introduced by Kim et al. [204] for the synthesis of a 27-member pool library of indoles (three pools by nine individuals). The structure of the dendritic support, which was prepared condensing the commercially available starburst polyamidoamine (PAMAM) dendrimer with the 4-hydroxymethyl benzoic acid (HMB) linker, is given in Figure 7.24. 

The use of dendrimers as supports for homogeneous catalysts was first reported by van Leeuwen and coworkers in 1995 (122). Oligo-carbosilane dendrimers were developed for this purpose (123). The open structure and solubility of dendrimers allow the attached catalysts to behave like... 

The class of so-called soluble supports, including PEGs, non-cross-linked PS, and the recently introduced high-loading dendrimers, will be covered in Section 8.5. 

Figure 8.51 Synthesis and purification of the discrete (L25) and the pool (L26) indole libraries using dendrimer soluble supports.

Besides the use of homogeneously soluble polymethacrylates or poylstyrene, as for the examples described above, other soluble supports may be used in order to yield a catalyst which can be retained by ultra- or nanofiltration membranes. Several groups have introduced catalysts (chiral and nonchiral) coupled to dendrimers and dendrimer-like structures [54, 59-76]. Compared with catalysts coupled to polymers, such complexes offer the advantage of a more defined structure. Thus, the number of active sites can be controlled more accurately. As these will be present at the surface of a globular structure they will be easily accessible. 

Dendrimers are a class of macromolecules with highly branched and well-defined structures, and have recently attracted much attention as soluble supports for (chiral) catalyst immobilization [55-65]. As stated above, the catalysts anchored onto or into insoluble supports often possess an uneven catalytic site distribution and partly unknown structures, and generally suffer from diminished activity due to the mass transfer hmitations. Dendrimers, on the other hand, allow for the precise construction of catalyst structures with uniformly distributed catalytic... 

Since the pioneering studies reported by van Koten and coworkers in 1994 [20], dendrimers as catalyst supports have been attracting increasing attention. The metaUodendrimers and their catalytic applications have been frequently reported and reviewed [7-15]. As a novel type of soluble macromolecular support, dendrimers feature homogeneous reaction conditions (faster kinetics, accessibility of the metal site, and so on) and enable the application of common analytical techniques such as thin-layer chromatography (TLC) and nuclear magnetic resonance... 

Based on this concept, Seebach et al. developed the first example of TADDOL-cored dendrimers (Figure 4.41) immobilized in a PS matrix [116]. The resultant internally dendrimer-functionalized polymer beads were loaded with Ti(OiPr)4, leading to a new class of supported Ti-TADDOLate catalysts for the enantioselective addition of diethylzinc to benzaldehyde. Compared to the conventional insoluble polymer-supported Ti-TADDOLate catalysts, these heterogeneous dendrimer catalysts gave much higher catalytic activities, with turnover rates close to those of the soluble analogues. The polymer-supported dendrimer TADDOLs were recovered by simple phase separation and reused for at least 20 runs, with similar catalytic efficiency. 

Soluble dendrimers bearing catalytic centers located at the periphery can be covalently attached onto the surface of conventional solid supports (such as polymer beads or silica gels), leading to another type of solid-supported dendrimer catalyst. It is expected that this type of immobihzed catalysts would combine the advantages of both the traditional supported catalysts and the dendrimer catalysts. First, the catalytically active species at the dendrimer surface are more easily solvated, which makes the catalytic sites more available in the reaction solutions (relative to cross-hnked polymers). Second, the insoluble supported dendrimers are easily removed from the reaction mixtures as precipitates or via filtration (relative to soluble dendrimers). These solid-supported peripheraUy functionalized chiral dendrimer catalysts have attracted much attention over the past few years [12, 113], but their number of applications in asymmetric catalysis is very limited. 

A related technique is based on soluble dendrimers as support (dendrimer-supported combinatorial chemistry, [76]). The feasibility of the approach was demonstrated by the synthesis of a small library of indoles. The synthesis started from an a-amino acid that... 

Reetz and co-workers reported on a DAB dendrimer as a soluble support, functionalized with diphenylphosphine groups at the periphery. The corresponding Pd complexes were used for Pd-catalyzed allylic amination to yield N-[3-phenyl-2-propenyl]morpholine in a continuous membrane reactor (6) [11],... 

Fourth- and fifth-generation phosphine-functionalized DAB dendrimers were applied, for which 100% conversion was obtained at the beginning. A 20% decrease was observed after 100 h, as well as palladium leaching between 0.07 and 0.14% per residence time. The soluble support, on the other hand, was completely retained in the membrane reactor. 

It should be mentioned here that soluble supports are not always innocent systems but can in fact alter the reaction in rather unexpected ways Cole-Hamilton and coworkers reported on dendrimers with 16 PPh2 groups on the periphery. This system was applied in the Rh-catalyzed hydroformylation of 1-octene and linear/branched ratios (l/h) of 13.9 were obtained, while a small-molecule analogue showed an l/b ratio of 3.8 (13) [24]. 

The binding of catalysts to soluble supports has the advantage that the catalytically active sites are uniformly distributed throughout the reaction media, as for the unsupported homogeneous counterparts. Furthermore, supported catalysts -especially dendritic systems - can sometimes show even higher selectivities than their small-molecule counterparts. Dendrimers as soluble supports, however, are not always easy to synthesize and usually require tedious synthetic protocols. 

Dendrimers are of interest as soluble supports for homogeneous catalysis since their large size enables recycling by membrane separation techniques. 

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