Dendrimers as soluble supports

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. 

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 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, 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... 

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... 

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

In addition to dendrimers, hyperbranched polymers have been used by several groups as soluble supports for catalysts [7, 17]. These supports are polydisperse and randomly branched, and, since they are prepared in a single reaction step, are generally much cheaper materials. Nevertheless, it has been shown that catalysts immobilized on hyperbranched polymers may possess similar properties as dendritic systems [18]. Therefore, dendritic catalysts serve as ideal model systems for catalysts attached to hyperbranched polymers. We functionalized several hyperbranched polyethyleneimines (PEIs) employing the peptide coupling protocol in reactions with the pyrphos linker system. The pyrphos-rhodium complexes bound to the hyperbranched polymers were also found to be active catalysts for the hydrogenation ofZ-methyl-a-acetamidocinnamate [16]. As observed for the... 

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... 

The supramolecular guest—Pd—dendrimer complex was found to have a retention of 99.4% in a CFMR and was investigated as a catalyst for the allylic ami-nation reaction. A solution of crotyl acetate and piperidine in dichloromethane was pumped through the reactor. The conversion reached its maximum ca. 80%) after approximately 1.5 h (which is equivalent to 2—3 reactor volumes of substrate solution pumped through the reactor). The conversion remained fairly constant during the course of the experiment (Fig. 8). A small decrease in conversion was observed, which was attributed to the slow deactivation of the catalyst. This experiment, however, clearly demonstrated that the non-covalently functionalized dendrimers are suitable as soluble and recyclable supports for catalysts. 

Abstract Enantioselection in a stoichiometric or catalytic reaction is governed by small increments of free enthalpy of activation, and such transformations are thus in principle suited to assessing dendrimer effects which result from the immobilization of molecular catalysts. Chiral dendrimer catalysts, which possess a high level of structural regularity, molecular monodispersity and well-defined catalytic sites, have been generated either by attachment of achiral complexes to chiral dendrimer structures or by immobilization of chiral catalysts to non-chiral dendrimers. As monodispersed macromolecular supports they provide ideal model systems for less regularly structured but commercially more viable supports such as hyperbranched polymers, and have been successfully employed in continuous-flow membrane reactors. The combination of an efficient control over the environment of the active sites of multi-functional catalysts and their immobilization on an insoluble macromolecular support has resulted in the synthesis of catalytic dendronized polymers. In these, the catalysts are attached in a well-defined way to the dendritic sections, thus ensuring a well-defined microenvironment which is similar to that of the soluble molecular species or at least closely related to the dendrimer catalysts themselves. 

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... 

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. 

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. 

As shown in Scheme 12.16, Josiphos ligands have been covalently attached to dendrimers [60], inorganic supports or organic polymers [45], as well as to vehicles which renders them soluble in ionic liquids [58] or water [61]. 

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... 

Poly(ethylene oxide) (PEO) has been employed frequently as a water-soluble catalyst support [9]. Further water-soluble polymers investigated include other linear polymers such as poly(acrylic acid) [10], poly(N-alkylacrylamide)s [11], and copolymers of maleic anhydride and methylvinylether [12], as well as dendritic materials such as poly(ethyleneimin) [10a, c] or PEO derivatives of polyaryl ethers [13]. The term dendritic refers to a highly branched, tree-like structure and includes perfectly branched dendrimers as well as statistically branched, hyperbranched macromolecules. 

The use of soluble polymers or dendrimers as chiral catalyst supports is another interesting way for catalyst separation [13]. Behaving like a homogeneous catalyst during the reaction, the catalyst can easily be separated by precipitation at the end of the reaction. High catalytic activities were reported using this approach. In addition, even use in membrane reactors may be possible using the ball-shaped dendrimers. 

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