Dendrimers enantioselective complexation

Pu et al.158,159 have used 4,4, 6,6 -tetrabromo-l,l -bi-2-naphthol to construct a novel series of rigid and cross-conjugated optically active dendrimers. Following complexation with Ti(0 Pr)4, the chiral dendrimer exhibited high enantioselectivity in the catalysis of the reaction of 1-naphthaldehyde with diethylzinc notably, the system catalyzed this reaction with 100% conversion and 90% ee in 5 hours without side products. The advantage of this metalloden-drimer over BINOL was that it could be easily removed from the reaction mixture by simple precipitation with MeOFl. 

Seebach et al. met the challenge of synthesizing chiral dendrimers to investigate the influence of chiral building blocks on the chirality of the whole molecule and to determine whether enantioselective complexation was possible. [45] They achieved dendrimers with a chiral nucleus as well as dendrimers with additional chiral branches. The optical activity of dendrimers with only a chiral nucleus decreases with increasing... 

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. 

Brunner et al. [26] synthesized and applied so-called dendrizymes in enan-tioselective catalysis. These catalysts are based on dendrimers which have a functionalized periphery that carries chiral subunits, (e.g. dendrons functionalized with chiral menthol or borneol ligands). The core phosphine donor atoms can be complexed to (transition) metal salts. The resultant dendron-enlarged 1,2-diphosphino-ethane (e.g. 16, see Scheme 17) Rh1 complexes were used as catalysts in the hydrogenation of acetamidocinnamic acid to yield iV-acetyl-phenylalanine (Scheme 17) [26]. A small retardation of the hydrogenation of the substrate was encountered, pointing to an effect of the meta-positioned dendron substituents. No significantly enantiomerically enriched products were isolated. However, a somewhat improved enantioselectivity (up to 10-11% e.e.) was... 

Kollner et al. (29) prepared a Josiphos derivative containing an amine functionality that was reacted with benzene-1,3,5-tricarboxylic acid trichloride (11) and adamantane-l,3,5,7-tetracarboxylic acid tetrachloride (12). The second generation of these two types of dendrimers (13 and 14) were synthesized convergently through esterification of benzene-1,3,5-tricarboxylic acid trichloride and adamantane-1,3,5,7-tetracarboxylic acid with a phenol bearing the Josiphos derivative in the 1,3 positions. The rhodium complexes of the dendrimers were used as chiral dendritic catalysts in the asymmetric hydrogenation of dimethyl itaconate in methanol (1 mol% catalyst, 1 bar H2 partial pressure). The enantioselectivities were only... 

Does the chiral core unit permit enantioselective (dendrimer) host/(substrate) guest complexation in the interior of the dendrimer scaffold ... 

Measurement of circular dichroism can even permit elucidation of relatively small structural changes. CD spectroscopy is also suitable for the solution of specific application-relevant questions. Studies of the sensor properties of chiral dendrimers make use of the fact that complexation of chiral guest molecules induces changes in the CD bands of the host dendrimers. Thus guest-selective chiroptical effects observed in titration experiments with enantiomeric guest molecules give an indication of the potential of the chiral dendrimer to act as an enantioselective sensor [87]. 

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. 

Chan et al. synthesized first- and second-generation dendrimers containing up to 12 chiral diamines at the periphery (Fig. 8) [29]. Their ruthe-nium(II) complexes displayed high catalytic activity and enantioselectivity in the asymmetric transfer hydrogenation of ketones and imines. Quantitative yields, and in some cases a slightly higher enantioselectivity compared to those of the monomeric systems (up to 98.7% ee), were obtained. 

Seebach introduced a novel concept for the immobilization of chiral ligands in PS. The ligand of choice was placed in the core of a styryl-substituted dendrimer 134, which was copolymerized with styrene under suspension polymerization conditions to give the polymeric chiral ligand 135 [74]. The corresponding polymeric (salen) Mn complexes were used to catalyze the enantioselective epoxidation of alkene (Scheme 3.38), with the polymeric complexes being recycled ten times... 

Seebach et al.150,151 synthesized a hexa-armed dendrimer attached the C2 symmetry ligand, TADDOL (a,a,a, a -tetraaryl-l,3-dioxolane-4,5-dimethanol), complexing withTi(OCHMe2)4 at the periphery. Using this chiral metallodendrimer, the enantiomeric addition152 of diethylzinc to benzaldehyde proceeded with the same enantioselectivity (ee, 97%) as that of the monomeric chiral catalyst. Since this metallodendrimer had a molecular weight of only 3833 Da, its recovery... 

One of the first applications of dendrimers as organometallic hosts was their use as enantioselective catalysts. Indeed, dendrimers that are functionalized with transition metals in the core potentially can mimic the properties of enzymes. Brunner introduced the term dendrizymes for core-functionalized transition metal catalysts which might be used in enantioselective catalysis. The dendrimeric organometallic complex shown in Figure 34 is an example of such a dendrizyme inside which the chiral dendritic branches create a chiral pocket around the transition metal. 

A number of catalysts with the catalytic site in the dendrimer core has also been used in asymmetric hydrogenation. A rhodium complex with dendrimer diphos-phine with menthyl groups in its branches as a catalyst in acetamidocinnamic acid hydrogenation exhibited low enantioselectivity. For a catalyst where dendrimers were at the meta positions of phosphine, the reaction rate was substantially higher than that for a low molecular weight analogue and for a catalyst where dendrimers were at positions 2 and 5 of phosphine, the reaction rate was much lower [134-137],... 

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