TADDOL dendritic

Not unexpectedly, a chiral TADDOL dendritic catalyst292 demonstrated a slight reduction in enan-... 

To increase efficiency and ease of product separation from reaction mixtures, we also prepared styryl-substituted TADDOL-dendrimers that can act as crosslinkers in styrene suspension polymerizations, and thus lead to beads with intimately incorporated TADDOL sites [106,107]. Due to the presence of the con-formationally flexible dendritic spacers between the chiral ligand and the poly-... 

Fig. 30. Dendritic TADDOL derivatives carrying the catalytically active site either at the periphery (84) or in the center (85) [105,106]...

Following a procedure previously employed for simple styryl TADDOLs [105], dendritic styryl-substituted TADDOLs were copolymerized with styrene... 

Employing 0.2 equiv. of polymer-bound dendritic Ti-TADDOLates of type 89 (1st and 2nd generation) enantioselectivities up to 98 2 were observed (Fig. 31). This value is comparable to those obtained in heterogeneous reactions using non-dendritic, polymer-bound analogs 88 (er up to 98,5 1,5 [ 105 ]) and with the... 

Fig. 31. Selectivity comparison for the enantioselective addition of Et2Zn to benzaldehyde using different dendritic and non-dendritic homogeneous and heterogeneous Ti-TADDOLates as chiral catalysts [107,110], (S)-.(R) ratios refer to the 1-phenyl-propanol formed...

A comparison of the rates showed that the polymer-bound Ti-TADDOLate 88 and the dendritic polymer 89 catalyze the Et2Zn-to-PhCHO addition at a similar fast rate as the monomeric TADDOLate 86 and the dendritic TADDOLate 87 in homogeneous solution [107,112]. Further experiments also with other ligands are being carried out in our laboratories. 

Seebach and co-workers copolymerized a dendritically modified TADDOL ligand with styrene (Figure 9). When associated with Ti(OiPr)4, the immobilized catalyst gave a very high ee (98%) for more than 20 runs in the enantioselective addition of diethylzinc to benzaldehyde95 96... 

So far, few data are available which allow the comparison of differences in efficacy and selectivity of one catalytic system attached to different supports. As far as the TADDOLate complexes are concerned, no clear rules can be drawn. Polystyrene-based catalysts derived from (8) and (10) show similar enantioselectivities and reaction rates. Differences appear, however, when comparing them with a polystyrene-embedded dendritic ligand system, generated by co-polymerization from TADDOL-derivative (32) (Scheme 4.18) which is described in Section 4.3.2.1. Re-cydabihty seems to be easier for the dendritic catalyst and the enantioselectivity. 

As has been described in Section 4.2.3, immobilized TADDOL-derivatives are particularly important catalytic species which can be applied to asymmetric synthesis in many ways. Seebach et al. developed a dendritic elongated TADDOL-deri-vative (32) that could be embedded in polystyrene by copolymerization (Scheme 4.18). Upon treatment with Ti(OiPr)4 the chiral polymeric diisopropoxy-Ti-TAD-... 

Since the pioneering studies of asymmetric catalysis with core-functionalized dendrimers reported by Brunner (88) and Bolm (89), several noteworthy investigations have been described in this field. Some examples of the dendritic effects observed in enantioselective catalysis with dendrimers having active sites in the core were discussed in Section II, such as the catalytic experiments with TADDOL-cored dendrimers described by Seebach et al. (59) the asymmetric addition of Et2Zn to aldehydes catalyzed by core-functionalized phenylacetylene-containing dendrimers reported by Hu et al (42)-, the asymmetric hydrogenation investigations with (R)-BINAP core-functionalized dendrimers synthesized by Fan et al. (36) or the results... 

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]. 

A dendritic catalyst 9, which like 7 and 8 has a chiral metal complex as core, was synthesised by Seebach et al. [54, 55]. The core building block was a,a,a ,a -tetraaryl-l,3-dioxolan-4,5-dimethanof (TADDOL), to which both chiral and achiral dendrons and those with peripheral octyl groups can be linked (Fig. 6.36, cf. Section 4.2.3, Fig. 4.62). 

On use as homogeneous catalysts in the asymmetric reductive alkylation of benzaldehyde with diethylzinc to form secondary alcohols, the corresponding dendritic titanium-TADDOL complexes having either chiral or achiral dendrons gave enantiomeric excesses (ee) of up to 98.5 1.5 at a conversion of 98.7% (for the catalyst with GO dendrons). With larger dendrons the reduction of the ee to 94.5 5.5 (G4) remained within reasonable limits, while the drop in conversion to 46.8% (G4) proved to be drastic. In comparison, the unsubstituted Ti-TAD-DOL complex gave an ee of 99 1 with complete conversion. This negative den-... 

Brunner s concept of attaching dendritic wedges to a catalytically active metal complex represented the first example of asymmetric catalysis with metal complex fragments located at the core of a dendritic structure [5,6]. Important early examples of catalysts in core positions were Seebach s TAD-DOL systems (TADDOL = 2,2-dimethyl-a,a,a/,a/-tetraphenyl-l,3-dioxolane-4,5-dimethanol) [38,39]. In general, the catalytic performance of such systems was either unchanged with respect to the simple mononuclear reference system or significantly lower. In no case has the potential analogy of this core fixation and the existence of efficient reactive pockets in enzymes been vindicated. This may be due to the absence of defined secondary structures in the dendrimers that have been employed to date. 

Scheme 9 Dendronized TADDOL ligands which are cross-linked to form a dendritic network [58]...

Ar = polystyrene supported dendritic TADDOL with aromatic tether Ref. 25 ... 

Several researchers have reported synthetic approaches based on asymmetric Diels-Alder reactions catalyzed by TADDOL-Ti complexes [117-120]. Dendritic [121] and polymer-supported TADDOL-Ti complexes [122] have also been employed as recoverable and reusable catalysts to give comparatively high enantioselectivity. Transition-state models have been proposed independently by several groups for TADDOL-type titanium catalysis [121,123]. 

Hyperbranched and dendritic macromolecules have recently been the subject of considerable interest. Bolm developed chiral hyperbranched macromolecules 57 that catalyzed the enantioselective addition of diethylzinc to benzaldehyde [75]. The enan-tiocontrol of the hyperbranched chiral catalysts was slightly lower than for the low-molecular-weight catalyst. TADDOLs linked with dendritic molecules have been synthesized [59]. For example, use of the first generation dendrimer 58 with six terminal TADDOL units resulted in high enantioselectivity. 

Convergent dendrimers, with their versatile three-dimensional scaffold, may be tailored to mimic, perhaps crudely, some elements of enzymatic structures. Numerous catalytic moieties, including manganese porphyrins,253,254 bis(oxazoline) copper complexes,304 305 tertiary amines,306 binaphthol titanium complexes,285 307 titanium taddolates,292,308 thiazolio-cyclophanes,309 and fullerene-bound bisoxazoline copper complexes,310 have been incorporated at the core of dendritic molecules to determine the effect of dendritic encapsulation on their catalytic activity. 

Nonracemic Ti-BINOLate (BINOL = l,l -bi-2-naplilli()l) and Ti-TADDOLate (TADDOL = a,a,a, a -tetraaryl-2,2-dimethyl-l,3-dioxolan-4,5-dimethanol) complexes are also effechve chiral catalysts for the asymmetric alkylation of aldehydes [9-11]. Seebach developed polystyrene beads with dendritically embedded BINOL [9] or TADDOL derivatives 11 [10, 11]. As the chiral ligand is located in the core of the dendritic polymer, less steric congeshon around the catalyhc center was achieved after the treatment with Ti(OiPr)4. This polymer-supported TiTADDOLate 14 was then used for the ZnEt2 addition to benzaldehyde. Chiral 1-phenylpropanol was obtained in quantitahve yield with 96% ee (Scheme 3.3), while the polymeric catalyst could be recycled many times. 

Brunner s concept (dendrizyme) of attaching dendrihc chiral wedges to a catalytically achve achiral metal complex represents the first example of asymmetric catalysis using a core-funchonalized dendrimer catalyst [21]. In view of the extremely poor asymmetric induction effected by the chiral dendritic shucture, the bulk of the attenhon has been focused on the immobilizahon of the well-established chiral hgands and/or their metal complexes into an achiral dendrimer core. The important early examples included TADDOL-centered chiral dendrimers, which were reported by Seebach et al. in 1999 [28]. In this section, we ahempt to summarize the recently reported chiral core-funchonalized dendrimers with special emphasis on their applications in asymmetric synthesis. 

Styryl-terminated Frechet-type dendrimers have been introduced as novel polymer crosslinkers by Seebach et al. [43-45]. They are constituted of four to 16 peripheral styryl units attached to aryl end branches of dendritic TADDOL, BINOL or Salen ligands and were copolymerised with styrene by suspension polymerisation. The catalytic performance of the polymer-bound catalyst was identical to that of the homogeneous analogues however, the supported catalysts could be used in many consecutive catalytic runs with only small loss in catalytic activity. A major drawback of fixing the catalytic unit in the core of the crosslinker is the poor loading capacity of the final polymer (0.13-0.20 mmol g 0> especially when high amounts of catalysts (10-20 mol%) are needed. 

Very recently, Seebach and coworkers reported a different approach for the immobilisation of TADEXDL derivatives. Dendritically substituted TADDOLs (90) were co-polymerised with styrene in a suspension polymerisation procedure and subsequently transformed into their titanium complexes. 

A polymer-bound catalyst of type 86 gave also quantitative conversion and 96% e.e. whereas the reaction rate was much smaller. The dendritically substituted TADDOLate seems more accessible for the substrates than the traditionally linked derivatives. 

Scheme 13. Comparison of Two Polymer-Bound Ti-TADDOLates Generated after Cross-Linking Polymerization of Styrene with Styryl-Substituted TADDOL Monomers (see Scheme 12). Best reproducibility is observed vdth materials of low loading degree (0.10 mmol/g). According to elemental analysis (and rate measurements), ca. 90% of the TADDOL moieties introduced into the polymer (with the monomeric, cross-linking styryl-TADDOLs) carry a Ti-atom [78] [79] and are thus not buried inaccessibly in the cross-linked polymer The dendritic polymer performs better, as far as enantioselectivity of the Et2Zn addition to PhCHO is concerned there is no erratic up and down, and the value obtained in the 20th run is identical to that of the first run (within experimental error) [79].

Again, the variability of TADDOL synthesis was instrumental for preparing the necessary precursors Scheme 12). It turned out that it was worthwhile to learn the technique of suspension polymerization [21] for the preparation of self-made beads loaded with TADDOLs multiple applications [83] with dendritically embedded TADDOL disclosed unique material properties of this new type of cross-linked polystyrene Scheme 13). The enantioselectiv-ity, the rate of reactions e.g., in the Ti-TADDOLate-catalyzed addition of Et2Zn to PhCHO), and the swelling properties of the material remained constant after 20 and more runs (with the same batch of beads) (see Scheme 14). 

Also, while the dendritic TADDOL polymer gave a somewhat slower tita-nate catalyst for the above mentioned reaction than the simple copolymerized TADDOL, a unique feature emerged with the former Scheme 14) the monomeric, dendritically substituted Ti-TADDOLate was found to be slower than the polymeric one (under diffusion-controlled conditions) Thus, our investigations on chiral dendrimers (review [84]) have fertilized the TADDOL work, and they may lead to a new type of high-performance polymer-bound reagents, beyond the TADDOLs. 

In 2002, the authors evaluated dendritically crosslinked catalyst 45b,c (see Figure 7.3) prepared from a 1 1 mixture of dendritic TADDOL derivatives and corresponding X2Ti(OiPr)2 (Scheme 7.52). Even though the performance was slightly lower than homogeneous conditions, the dendritic catalysts 45b,c showed to be very competitive and catalysed the reaction with... 

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