Catalyst supports chiral

Keywords Asymmetric synthesis, Chiral catalysis, Mo-based catalysts, Natural product synthesis, Olefin metathesis, Recyclable catalysts, Ru-based catalysts, Supported chiral catalysts... 

The polymer-supported chiral oxazaborolidinone catalyst 5 prepared from valine was found by Ituno and coworkers to be a practical catalyst of the asymmetric Diels-Alder reaction [7] (Scheme 1.12). Of the several cross-linked polymers with a... 

Keywords acrylates, acrylamides, fumarates, a, -unsaturated ketones, vinyl ethers, vinyl sulphoxides, chiral dienophiles, chiral dienes, chiral catalysts polymer-supported chiral Lewis acids... 

Some attempts to obtain a polymer-supported catalyst for chiral asymmetric allylic alkylation have been reported with some success in respect of catalyst recycling on activity, but with unsatisfactory results concerning enantioselectivity.188,189... 

Asymmetric catalysis provides access to several synthetically important compounds, and immobilized catalysts together with solid-supported chiral ligands have been equally instrumental. Chiral ligands immobilized on a solid support provide the advantage of being rapidly removable post-reaction while retaining their activity for further applications [139]. 

Kragl and Dreisbach reported on the asymmetric diethylzinc addition to benzaldehyde using a chiral homogeneous catalyst supported on a soluble polymethacrylate.[55] l, L-Diphenyl-L-prolinol was bound to a copolymer from 2-hydroxyethylmethacrylate and octadecylmethacrylate forming a soluble catalyst with a Mw of 96 000 (Figure 4.39). 

Scheme 39.7 Continuous-flow hydrogenation of dimethyl itaconate (15) using a solid-supported chiral catalyst and scC02 as the mobile phase (PTA= H3P40PW12).

The preparation of this type of catalyst is quite simple. HPAs such as phos-photungstic acid were adsorbed onto inorganic supports such as clays, alumina, and active carbon. Subsequently, the metal complex was added to form the immobilized catalyst. If necessary, the catalyst can be pre-reduced. These types of catalysts were developed mainly for enantioselective hydrogenations. For instance, a supported chiral catalyst that was based on a cationic Rh(DIPAMP) complex, phosphotungstic acid and alumina showed an ee-value of 93% with a TOF of about 100 IT1 in the hydrogenation of 2-acetamidoacrylic acid methyl ester (Fig. 42.4 Table 42.2). 

The polymer-supported chiral phosphine obtained (Fig. 42.15) was treated with an Rh precursor and used for the enantioselective hydrogenation of dehydroamino acid derivatives. The obtained catalyst gave up to 82% ee, albeit with still low activity. Stille has developed this immobilization technique further by even more careful tuning of the polarity of the support with that of the reaction medium. For example, he introduced DIOP to a monomer vinylbenzalde-hyde in reactions analogous to those shown for the polymer in Figure 42.11. 

Method B (catalysed by polymer-supported chiral fl-hydroxyamines) The aldehyde (1 mmol) is added to the polymer-supported catalyst (0.298 g) in n-C6Hu (2 ml) at 0°C and the mixture is stirred for 15 min. The dialkylzinc (1M in rt-C6H 4, 2.2 ml) is added and the mixture is stirred for 1-8 days at 0°C. The reaction is quenched with aqueous HCI (1M, 5 ml) and the mixture is filtered and extracted with CH2C12 (3x10 ml). The dried (Na2S04) extracts are evaporated to yield the chiral secondary alcohol. 

Other examples involved the use of chiral Schiff base-zinc complexes as catalysts [33 a] and polymer-supported chiral N-tritylaziridino alcohols as catalysts. The stereoselectivity was reported to be up to 97% ee for aUphatic and up to 96% ee for aromatic aldehydes [103]. 

Asymmetric Diels-Alder reactions have also been achieved in the presence of poly(ethylene glycol)-supported chiral imidazohdin-4-one [113] and copper-loaded silica-grafted bis(oxazolines) [114]. Polymer-bound, camphor-based polysiloxane-fixed metal 1,3-diketonates (chirasil-metals) (37) have proven to catalyze the hetero Diels-Alder reaction of benzaldehyde and Danishefsky s diene. Best catalysts were obtained when oxovanadium(lV) and europium(III) where employed as coordinating metals. Despite excellent chemical yields the resulting pyran-4-ones were reported to be formed with only moderate stereoselectivity (Scheme 4.22). The polymeric catalysts are soluble in hexane and could be precipitated by addition of methanol. Interestingly, the polymeric oxovanadium(III)-catalysts invoke opposite enantioselectivities compared with their monomeric counterparts [115]. 

Tab. 11.13 Catalytic asymmetric olefin metathesis reactions promoted by supported chiral catalyst (81). >...

The polymer-supported chiral catalyst is recyclable. The catalytic AROM/CM example shown in Scheme 11.12 is representative. Excellent enantioselection and ef... 

This tethered ferrocenyl-based Pd complex on MCM-41 (17) was then used for the catalytic amination reaction between cinnamyl acetate and benzylamine (40 °C, THF) [59]. In this case, confinement of the catalyst results in profound changes in regio- and enantioselectivity. When the homogeneous equivalent is used to catalyze the reaction, the straight chained derivative is the sole product. Similar results (only 2% of the branched product) were obtained when the catalyst was tethered to the surface of the non-porous silica Cabosil. When tethered inside the pores of MCM-41 a major change occurred in that now the branched product accounts for about 50% and a change in e.e. from 49% e.e. when anchored to the Cabosil support to +99% when anchored inside the MCM-41 pore could be observed. If the catalyst s chirality was reversed in the MCM-41 immobihzed case, so was the chirality of the product (measured at 93% e.e.) [60]. 

A chiral polymer-bound metathesis catalyst has been developed. The supported chiral complex 75d shows appreciable levels of reactivity and excellent enantios-electivity. " This complex 75d can be recycled and easily removed from unpurified mixtures. In the first and second cycles of the recycle experiment, almost the same reactivity has been shown. In the third cycle, high enantioselection and conversion are still obtained, but catalyst activity is notably diminished ... 

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). 

Enantioselective reduction of jS-keto nitriles to optically active 1,3-amino alcohols has been carried out in one step using an excess of borane-dimethyl sulfide complex as a reductant and a polymer-supported chiral sulfonamide as a catalyst with moderate to high enantioselectivity (Figure 3.11). The facile and enantioselective method to prepare optically active 1,3-amino alcohols has been used to prepare 3-aryloxy-3-arylpropylamine type antidepressant drugs, for example (l )-fluoxetine. 

Preparation of nonracemic epoxides has been extensively studied in recent years since these compounds represent useful building blocks in stereoselective synthesis, and the epoxide functionality constitutes the essential framework of various namrally occurring and biologically active compounds. The enantiomericaUy enriched a-fluorotropinone was anchored onto amorphous KG-60 silica (Figure 6.6) this supported chiral catalyst (KG-60-FT ) promoted the stereoselective epoxidation of several trans- and trisubstituted alkenes with ees up to 80% and was perfectly reusable with the same performance for at least three catalytic cycles. 

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]. 

Although the main focus of our programs have been on issues of reactivity and enantioselectivity, we have recently begun to address the important issue of practicality in Mo-catalyzed asymmetric metathesis. Two key advances have been reported in this connection (1) The availability of a general chiral Mo catalyst that can be prepared in situ from commercially available compounds. (2) The synthesis of a recyclable polymer-supported chiral Mo catalyst. These advances are summarized below. 

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