Dendrimer-supported synthesis

The different carbosilane dendrimer supports (generation 0, 1 R=H, Me) were then used for the synthesis of the / -lactam (13). As shown in Scheme 7.2, the first step was again an immobilization of a carboxylic acid via ester bond formation. Treatment with LDA and ZnCl2 yielded in situ the corresponding zinc ester enolate (11) which reacts with N-(trimethylsilyl)phenylimine (12) to form the final four membered lactam ring (13). The last reaction step includes several intermediates. The last one is a supported /9-amino ester which undergoes spontaneous... 

The same authors recently described the synthesis of similar rhodium-complexed dendrimers supported on a resin having both interior and exterior functional groups. These were tested as catalysts for the hydroformylation of aryl alkenes and vinyl esters (52). The results show that the reactions proceeded with high selectivity for the branched aldehydes, with excellent yields, even up to the tenth cycle. The hydroformylation experiments were carried out with first- and a second-generation rhodium-complexed dendrimers as catalysts, with a mixture of 34.5 bar of CO and 34.5 bar of H2 in dichloromethane at room temperature. Each catalyst was easily recovered by simple filtration and was reusable for at least six more cycles without... 

The chemistry of carbonylation has long been known and widely applied in organic synthesis as a convenient, versatile, and powerful method [153-205]. Recently, Lu and Alper [206] investigated the catalytic efficiency of dendrimer-supported... 

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. 

It has been shown that dendrimer supports do not need to be perfect ligands for this application, which would make the synthesis costly. Highly branched polymers will give the same performance in catalysis, and their synthesis is much easier 126,127). 

Kim et al. (294) reported the synthesis of a small, 6-member array of discretes L25 and of a small 27-member pool indole library L26 using a commercially available, polyamide-based dendrimer support (8.107, Fig. 8.50) in which eight amino reaction sites per dendritic unit are present. The synthetic route for the preparation of the indole nuclei is reported in Fig. 8.51. Dendrimer 8.107 was first coupled to the base-labile... 

The thermal conversion of arylhydrazones in the presence of a protic acid or a Lewis acid to form an indole ring. See OweUen, R.J., Fitzgerald, J.A., Fitzgerald, B.M. et al.. The cyclization phase of the Fischer indole synthesis. The structure and significance of Pleininger s intermediate. Tetrahedron Lett. 18, 1741-1746, 1967 Kim, R.M., Manna, M., Hutchins, S.M. et al., Dendrimer-supported combinatorial chemistry, Proc. Natl. Acad. Sci. USA 93, 10012-10017, 1996 Brase, S., Gil, C., and Knepper, K., The recent impact of solid-phase synthesis on medicinally relevant... 

It is clear tliat the attachment of chiral catalysts to dendrimer supports offers a potential combination of the advantages of homogeneous and heterogeneous asymmetric catalysis, and provides a very promising solution to the catalyst-product separation problem. However, one major problem which limits the practical application of these complicated macromolecules is their tedious synthesis. Thus, the development of more efficient ways to access enantioselective dendritic catalysts with high activity and reusability remains a major challenge in the near future. 

Recently, Soai et al. reported the synthesis of series of chiral dendrimer amino alcohol ligands based on PAMAM, hydrocarbon and carbosilane dendritic backbones (Figure 4.31) [99-102]. These chiral dendrimers were used as catalysts for the enantioselective addition of dialkylzincs to aldehydes and N-diphenylphosphi-nylimines (Scheme 4.25). The molecular structures of the dendrimer supports were shown to have a significant influence on the catalytic properties. The negative dendrimer effect for the PAMAM-bound catalysts was considered due to the fact that the nitrogen and oxygen atoms on the dendrimer skeleton could coordinate to zinc. 

In 2002, Sasai et al. reported the synthesis of dendrimer heterobimetallic multi-funchonal chiral catalysts, containing up to 12 chiral BINOL units at the periphery (Figure 4.36) [107]. The insoluble dendrihc heterobimetallic mulhfunchonal chiral AlLibis(binaphthoxide) (ALB) complexes were obtained by treahng these dendrimer ligands with AlMcj and n-BuIi. The resulhng dendrimer-supported ALB... 

Concerning future work, an improvement might be the extension of the asymmetric catalytic nitroaldol reaction to the field of solid-support synthesis. An interesting contribution concerning the use of dendritic catalysts in the Henry reaction was reported very recently by Cossio et al. [48], who demonstrated that dendrimers based on achiral triethanolamine exhibit catalytic properties. Several nitroalkanols were synthesized with syn/anti ratio up to 2 1 (racemic syn- and anti-products). The design of enantiomerically pure dendrimers and their application to the field of asymmetric catalytic nitroaldol reaction should be of high interest. 

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... 

First investigations with cell cultures showed that certain dendrimers support the transfection of mammalian cells by plasmids. The controlled synthesis, low toxicity, and pH buffering eflect of dendrimers are the main criteria for dendrimers suitable for gene-transfer experiments. [44]... 

P. R. L. Malenfant, M. Jayaraman and J. M. J. Frdchet, Dendrimer-supported ohgothiophene synthesis aliphatic ether dendrimers in the preparation of ohgothiophenes with minimal substitution, Chem. Mater., 11, 3420-3422... 

Scheme 25 Synthesis of the dendrimer-supported phosphine catalyst synthesized by Reek, Meijer and coworkCTs. ...

Siani A, et al. Dendrimer-mediated synthesis of subnanometer-sized Rh particles supported on ZrOj. J Catal 2009 266 331-12. 

Hyperbranched Macromolecules. Because of their close structural and synthetic similarities to dendrimers, the comparison of hyperbranched macromolecules with their dendritic analogs has been studied by a number of groups. Ihre and Hult(7i) have recently reported the synthesis and characterization of the dendritic analogs of the commercially available hyperbranched polyesters, Boltron(D(7, based on 2,2-bis(hydroxymethyl)propionic acid, while Moor iJ) has reported a novel solid-supported synthesis of hyperbranched poly(phenylacetylenes) which are the hyperbranched analogs of Moore s well studied phaiylacetylene dendrimers(id). An intriguing study was also reported by Feast into the synthesis and physical properties of hyperbranched analogues of Tomalia s poly(amidoamine) dendrimers (77). 

Lu X, Imae T (2007) Dendrimer-mediated synthesis of water-dispersible carbon-nanotube-supported oxide nanoparticles. J Phys Chem C 111 8459... 

Huang W, Kuhn IN, Tsung C-K, Zhang Y, Habas SE, Yang P, Somorjai GA (2008) Dendrimer templated synthesis of one nanometer Rh and Pt particles supported on mesoporous silica catalytic activity for ethylene and pyrrole hydrogenation. Nano Lett 8 2027... 

A novel approach for the parallel synthesis of glycopeptides was suggested by Matsushita et al. (2013) by combining solid-phase peptide synthesis and dendrimer-supported enzymatic modifications. 

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]. 

Many opportunities conversely are supported by reversible reactions of QM despite the noted complications. One example includes the synthesis and chiral resolution of binaphthol derivatives by two cycles of QM formation and alkylation.77 The reversibility of QM reaction may also be integrated in future design of self-assembling systems to provide covalent strength to the ultimate thermodynamic product. To date, QMs have already demonstrated great success in supporting the opposite process, spontaneous disassembly of dendrimers (Chapter 5). 

Since the pioneering work on dendritic structures by Vogtle et al.,[28] dendrimers have attracted much attention. The synthesis and investigation of their structural properties became a new field in science. The application of dendrimers as support molecules for homogeneous catalysts was first reported by Van Koten et al. in 1994.[29] Dendrimers have the advantage of having perfect structures unlike polymeric structures and are... 

The authors thank the National Science Foundation (DMR) for the continued support of research in the field of dendrimer synthesis. Additional support by the ARO (MURI program) is also acknowledged with thanks. 

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. 

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