Chiral dendritic catalysts reactions

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. 

Recently, Majoral et al. described the synthesis of a third-generation phosphorus-containing dendrimer possessing 24 chiral iminophosphine end groups derived from (2S)-2-amino-l-(diphenylphosphinyl)-3-methylbutane (Fig. 11) [32]. The dendritic catalyst was tested in allylic substitution reactions, using rac-(.E)-diphenyl-2-propenyl acetate or pivalate as substrates. The observed enantioselectivities were good to excellent (max. 95% ee) in all reactions. After completion of the catalytic reaction, the catalyst could be reused at least twice after precipitation and filtration. A slight decrease... 

The first reported example using macromolecule-supported catalysts in latent biphasic systems was work by Chan s group that employed a dendrimer-bound BINAP 127 that was used to form a chiral ruthenium hydrogenation catalyst [164]. The dendritic Ru-BINAP complex formed from the reaction of [RuCl2(benzene)2]2 and 127 was successfully used in four cycles in the hydrogenation of 2-phenylacrylic acid (Eq. 65) in a 1 1 (vol/vol) ethanol/hexane mixture. Addition of 2.5 vol% water to this mixture produced a biphasic mixture where >99% of the dendritic catalyst was in the hexane phase. Addition of a fresh ethanolic substrate solution to this hexane phase produced another miscible solution of catalyst and substrate. The second and subsequent cycles of hydrogenation carried out in this manner led to consistent conversions of substrate with synthetic yields of >91% with e.e. values of 90%. 

Bohn and co-workers also studied diethylzinc addition to benzaldehyde with soluble polymeric catalysts [10]. Dendritic chiral catalysts consisting of poly(benzyl ethers) and chiral pyridyl alcohols (3) were used as organocatalysts for the asymmetric C-C linkage reaction. The enantiocontrol by the dendritic systems was slightly lower than that of the parent pyridyl alcohols (2-3% drop in ee) but the conversion toward the chiral secondary alcohol was actually slightly higher for the largest dendritic catalyst (84% versus 80% yield after 3 h of reaction time). In more... 

Pan et al. give an extensive review of immobilized asymmetric catalysts according to reaction classes and the land of support [9]. Saluzzo and Lemaire reviewed the use of polymer-supported BINAP for hydrogenation and hydrogen-transfer reduction with diamines or amino alcohols, respectively [10]. The immobilization and recycling of chiral catalysts was the topic of a recent book [11]. Dendritic catalysts... 

Portnoy and coworkers immobilized chiral hydroxyproline derivatives on polystyrene support functionalized with polyether dendrons (Scheme 15.45).These catalysts promoted the aldol addition of acetone to aromatic aldehydes with excellent enantioselec-tivities, significantly superior to those achieved in the same reaction with analogous catalyst lacking the dendritic interface. The same group prepared polymer-supported chiral bifunctional aminocarbamate and aminourea catalysts for nitro-Michael reaction (Scheme 15.46). However, in this case the dendritic catalysts were inferior to their simpler dendron-lacking analogues. 

Brunner et al. attached chiral branches to non-chiral catalytically active sites. With the aim to influence the enantioselectivity of transition metal catalyzed reactions they synthesized several dendritically enlarged diphosphines such as 81 [101] (Fig. 29). In situ prepared catalysts from [Rh(cod)Cl]2and81 have been tested in the hydrogenation of (a)-N-acetamidocinnamic acid. After 20 hours at 20 bar H2-pressure (Rh/substrate ratio 1 50) the desired product was obtained with an enantiomer ratio of 51 49. 

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). 

Transfer hydrogenation of ketones using metal complexes with a chiral water-soluble [97,98] and a dendritic ligand [99] was investigated for use in recycling catalysts. The reaction with immobilized catalysts has also been reported [100]. 

Measurements of molar rotation showed that this parameter is almost proportional to the number of chiral binaphthyl units and the molar rotation per binaphthyl unit varies only slightly. On catalysis of the Diels-Alder reaction of cyclopentadiene with 3-[(E)-but-2-enoyl]oxazolidin-2-one the branched catalysts 7 and 8 showed an approximately 25% higher reactivity than the monofunctional catalyst 6 however, the former led to just a slight improvement of ee and endo-selectivity compared to 6. It is thus inappropriate to speak of a dendritic effect on catalysis, although one does indeed exist in relation to the chiroptical properties. 

In the dendritic [Co(salen)] complexes prepared by Breinbauer and Jacobsen the dendrimer again serves as - covalent - support material for the catalytic entities attached to the periphery [62]. These dendritic Jacobsen catalysts were obtained by reaction of the corresponding PAMAM dendrimers with active ester derivates of chiral ]Co(II)-(salen)] units according to standard peptide coupling methods. In hydrolytic kinetic resolution of vinylcyclohexane oxide the dendrimer 14 (Fig. 6.40) showed a dramatically increased reactivity compared to the commercially available monomeric Jacobsen catalyst [63-67]. Whereas the latter merely gave a conversion of less than 1% with an indeterminable ee, 14 afforded a conversion of 50% with an ee of 98 2. 

In 2002, Sasai et al. reported the synthesis of dendritic heterobimetal-lic multi-functional chiral catalysts, containing up to 12 l,l/-bi-2-naphthol (BINOL) units at their terminal positions (Fig. 9) [30]. On treating these functionalized dendrimers with AlMe3 and n-Buli, insoluble metallated Al-Ii-bis(binaphthoxide) generation x (GX-ALB) catalysts were obtained, which showed moderate catalytic activity in the asymmetric Michael reaction of 2-cyclohexenone with dibenzyl malonate (Scheme 4). 

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