Dendrimer chiral

Chiral dendrimers based on oligonaphthyl cores and Fr chet-type poly(aryl ether) dendrons have been investigated [44]. The absolute configuration of these dendrimers remains the same as that of their chiral cores. Both the nature of the core and the generation play a role in determining the fluorescence quantum yield. 

The synthesis of chiral dendrimers from various building blocks, their - difficult - structure determinations, and their - potential - use in physiological applications, in bioassays, and in enantioselective catalysis are reviewed. 

Keywords Chiral dendrimers, dendrimers, asymmetric synthesis, asymmetric catalysis. 

Chiral Dendrimers Containing Oligo-(3-Hydroxybutanoate) Units. .139... 

Chiral dendrimers are a class of compounds which offer the possibility to investigate the impact of chirality in macromolecular systems. Their specific properties are based on their well defined highly ordered structures with nano-scopic dimension (in this report we refer to dendrimers if the molecule has a core with at least three branches attached and a defined structure otherwise we will use the term dendritic compound). 

Fig. 1. Introduction of one or more than one stereogenic elements (center, axis, plane or helix) leads to different types of chiral dendrimers...

Chiral Dendrimers and Dendritic Compounds Containing Unaltered Natural Building Blocks... 

The molar ellipticity of these dendrimers was found to increase proportional to the number of chiral end groups. This is to be expected, in the absence of interactions between the terminal tryptophane moieties. No higher-generation dendrimers of this type have been reported. Other amino-acid-containing chiral dendrimers have been described by Meijer et al. who attached various amino acid derivatives to the periphery of poly(propylene imine) dendrimers (see Sect. 3) and more recently by Liskamp et al. (modification of polyamide dendra) [22] and Ritter et al. (synthesis of grafted polymerizable dendrimers containing L-aspartic acid components) [23]. 

The latter is an interesting example of self-organizing chiral dendrimers. The construction of the dendrimer is based on the natural property of nucleic acids to recognize and specifically bind to complementary sequences. Pairwise hybridization of two designed DNA strands results in the formation of large monomers which have four single stranded arms and a double stranded waist (24, Fig. 12). 

Fig. 13. Chiral dendrimers of 2nd generation from trimesic and (i )-3-hydroxy-butanoic acid [56,57]...

The stereogenic centers of chiral dendrimers synthesized so far are either generated by asymmetric synthesis, or they are derived from molecules of the pool of chiral building blocks. The only investigation on chiral dendrimers, consisting of achiral building blocks exclusively, was published by Meijer et al., who synthesized dendrimers such as 31 [61] (Fig. 14). This compound ows its chiral-... 

Fig. 14. Chiral dendrimers 31 (prepared as racemic mixture) with a core chirality center. Compounds 32 and 34 are derived from (S)-solketal 33 as enantiopure precursor [61,64,66]...

At the beginning of investigations on chiral dendrimers in our own group was the question of how to synthesize chiral, non-racemic derivatives of tris(hydroxymethyl)-methane [82], which we wanted to use as dendrimer center pieces. We have developed efficient diastereoselective syntheses of such triols [83-85] from ( R)-3-hydroxybutanoic acid, readily available from the biopolymer PHB [59,60] (cf. Sect. 2.4). To this end, the acid is converted to the dioxanone 52 [86, 87], from which various alkylation products and different aldol adducts of type 53 were obtained selectively, via the enolate (Fig. 20). These compounds have been reduced to give a variety of enantiopure chiral building blocks for dendrimers, such as the core unit 54, triply branching units 55a and 55b or doubly branching unit 56 [1,88]. 

In 1994 we published the first chiral dendrimers built from chiral cores and achiral branches [ 1,89], see for instance dendrimer 57 with a core from hydroxy-butanoic acid and diphenyl-acetaldehyde and with twelve nitro-groups at the periphery (Fig. 21). As had already been observed with starburst dendrimers, compound 57 formed stable clathrates with many polar solvent molecules, and it could actually only be isolated and characterized as a complex [2 (57- EtO-Ac (8 H20))]. Because no enantioselective guest-host complex formation could be found, and since compounds of type 57 were poorly soluble, and could thus not be easily handled, we have moved on and developed other systems to investigate how the chirality of the core might be influencing the structure of achiral dendritic elongation units. 

Another possibility to find out more about the structure of these dendrimers was chosen by incorporating fluorine atoms. The use of 19F-NMR spectroscopy offered an additional tool to study the conformation of the dendrimer, especially with the fluorines attached close to the stereogenic centers [91 ]. Following our previously developed methods [92], fluorine-containing 1st- and 2nd-genera-tion chiral dendrimers such as 76 were synthesized (Fig. 24). 

Fig. 27. CD spectra of fully chiral dendrimers (Oth up to 4th generation of type 77) in CH2Cl and in CH3CN [94]...

In conclusion, we have learned a lot from studying chiral dendrimers, about the behavior of such large chiral molecules and about the contributions of the different building blocks to the whole structure. It remains a great challenge to rationalize the origin of the dramatic diastereoselectivity effects observed in the synthesis of certain chiral dendrimers. 

D. Seebach, P. B. Rheiner, G. Greiveldinger, T. Butz, H. Sellner, Chiral Dendrimers , Top. Curr. Chem, Vol 197 Dendrimers (Ed. F. Vogtle), Springer-Verlag, Berlin, Heidelberg 1998,125-164. 

A number of groups have reported the preparation and in situ application of several types of dendrimers with chiral auxiliaries at their periphery in asymmetric catalysis. These chiral dendrimer ligands can be subdivided into three different classes based on the specific position of the chiral auxiliary in the dendrimer structure. The chiral positions may be located at, (1) the periphery, (2) the dendritic core (in the case of a dendron), or (3) throughout the structure. An example of the first class was reported by Meijer et al. [22] who prepared different generations of polypropylene imine) dendrimers which were substituted at the periphery of the dendrimer with chiral aminoalcohols. These surface functionalities act as chiral ligand sites from which chiral alkylzinc aminoalcoholate catalysts can be generated in situ at the dendrimer periphery. These dendrimer systems were tested as catalyst precursors in the catalytic 1,2-addition of diethylzinc to benzaldehyde (see e.g. 13, Scheme 14). 

In a subsequent paper, the authors developed another type of silica-supported dendritic chiral catalyst that was anticipated to suppress the background racemic reaction caused by the surface silanol groups, and to diminish the multiple interactions between chiral groups at the periphery of the dendrimer 91). The silica-supported chiral dendrimers were synthesized in four steps (1) grafting of an epoxide linker on a silica support, (2) immobilization of the nth generation PAMAM dendrimer, (3) introduction of a long alkyl spacer, and (4) introduction of chiral auxiliaries at the periphery of the dendrimer with (IR, 2R)-( + )-l-phenyl-propene oxide. Two families of dendritic chiral catalysts with different spacer lengths were prepared (nG-104 and nG-105). 

Recently, dendrimers, which are hyperbranched macromolecules, were found to be an appropriate support for polymer catalysts, because chiral sites can be designed at the peripheral region of the dendrimers (Scheme 5). Seebach synthesized chiral dendrimer 14, which has TADDOLs on its periphery and used an efficient chiral ligand in the Ti(IV)-promoted enantioselective alkylation [21]. We developed chiral hyperbranched hydrocarbon chain 15 which has six p-ami-no alcohols [22], It catalyzes the enantioselective addition of diethylzinc to aldehydes. We also reported dendritic chiral catalysts with flexible carbosilane backbones [23]. 

Mention of chirality in dendritic architectures can be traced back to patents of Denkewalter et al., which describe the construction of peptide-like dendritic structures from L-lysine units [1]. In spite of the demanding nature of some of these syntheses, numerous chiral dendritic structures have meanwhile been prepared and characterised [2]. This cannot be explained solely by the somewhat academic interest in the effect of chiral monomeric building blocks on the chirality of the overall molecule. The prospect of using chiral dendrimers as model... 

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