Ru-BINAP

Reaction Characteristics of Immobilized Ru-BINAP Catalysts in Asymmetric Hydrogenation of Dimethyl itaconate... 

In this work, various Ru-BINAP catalysts immobilized on the phosphotungstic acid(PTA) modified alumina were prepared and the effects of the reaction variables (temperature, H2 pressure, solvent and content of triethylamine) on the catalytic performance of the prepared catalysts were investigated in the asymmetric hydrogenation of dimethyl itaconate (DMIT). 

Fig. 1. shows the P MAS NMR chemical shifts for the immobilized and homogeneous catalyst. The chemical shifts at the -15.2 and -13.7 ppm correspond to PTA while the chemical shifts in the range from 20 and 40 ppm correspond to phosphine oxide. The chemical shifts at the 66 and 118 ppm seems to be those of BINAP ligand, which is confirmed by the spectrum of Ru-BINAP catalyst. This spectrum shows that PTA exist in large amount on the surface of immobilized catalyst and that BINAP ligand is intact after immobilization. 

Fig. 1. P MAS NMR spectrum of (a)Ru-BrNAP/PTA/y-Al203, and (b)Ru-BINAP crt rlex In order to find the characteristics of the immobilized catalyst, asymmetric hydrogenation of the prochiral C=C bond was performed as a model reaction. Firstly, three different homogeneous Ru-BINAP complexes including [RuCl2((R)-BINAP)], [RuCl((R)-BINAP)(p-cymene)]Cl and [RuCl((R)-BINAP)(Benzene)]Cl were immobilized on the PTA-modified alumina. Reaction test of immobilized catalysts showed that [RuCl2((R)-BINAP)] was the most active and selective so all the experiment were done using this catalyst afterwards.

Reaction experiments were performed at the substrate to catalyst ratios between 250 and 5000 (Table 1). The immobilized catalyst showed a rather constant values of TOP and enantioselectivity in spite of the increase in the S/C ratio, even though these values were slightly lower than those of the homogeneous Ru-BINAP catalyst. After the reaction, the Ru content in the reaction mixture was measured by ICP-AES and was found to be under 2 ppm, the detecting limit of the instrument, indicating the at Ru metal didn t leach significantly during the reaction. These results show that the immobilized Ru-BINAP catalyst had stable activity and enantioselectivity and that the Ru metal complex formed a stable species on the alumina support. 

Effect of reaction conditions on the asymmetric hydrogenation of dimethyl itaconate over immobilized Ru-BINAP catalyst... 

Asymmetric hydrogenation of 2- Ru-BINAP-chiral S-Naprt)xen Pharma... 

The mechanism of such reactions using unsaturated carboxylic acids and Ru(BINAP)(02CCH3)2 is consistent with the idea that coordination of the carboxy group establishes the geometry at the metal ion.26 The configuration of the new stereocenter is then established by the hydride transfer. In this particular mechanism, the second hydrogen is introduced by protonolysis, but in other cases a second hydride transfer step occurs. 

The great selectivity of Ru-BINAP species is also evident when they are used in kinetic resolution of enantiomers. When a racemic allylic alcohol reacts with H2 in the presence of Ru-(A)-BINAP, the (R)-alcohol reacts preferentially, thus leaving the (S)-enantiomer unreacted (Equation (7)).71... 

Using unmodified Ru-BINAP and Rh-Et-DUPHOS catalysts Jacobs et al. performed hydrogenation reactions of dimethylitaconate (DMI) and methyl-2-acetamidoacrylate (MAA), respectively. [11,47] The continuous hydrogenation reaction was performed in a 100 mL stirred autoclave containing an MPF-60 membrane at the bottom, which also acts as a dead-end membrane reactor. The hydrogenation reactions will be discussed in paragraph 4.6.1. 

Dense membranes are a special type of polymeric membranes. Jacobs et al. published on the use of polydimethylsiloxane (PDMS) dense membranes in the hydrogenation of dimethylitaconate and acetophenone using standard homogeneous catalysts (see Section 4.6.1)[48]. The membranes were homemade from a PDMS solution in hexane, which was cross-linked in a vacuum oven at 100°C. The membranes were able almost completely to retain unmodified Ru-BINAP dissolved in isopropanol. However, as mentioned earlier, these applications will strongly depend on the size, i.e. molecular weight, of the substrate to be converted in order to guarantee a sufficient difference in size of the product and the catalyst to be retained. 

Another setup used for the hydrogenation of DMI with Ru-BINAP was equipped with dense PDMS elastomer membranes (Jacobs et al. [48]). The catalyst solution was present in a submerged membrane system, prepared as a sealed PDMS capsule . The catalytically active complex was retained by the membrane while substrate and products, dissolved in the bulk phase, could cross the membrane under the influence of the concentration difference without the need for mechanical pressure. 

A series of /3-keto phosphonates have been hydrogenated with the Ru-BINAP system to give various chiral /3-hydroxyl phosphonates (Equation (75)).286 An Ru-MeO-BIPHEP catalyst is also effective for this transformation.287 /3-Keto thiophosphonates can also be smoothly transformed into /3-hydroxyl thiophosphonates with high ee.287... 

An efficient dynamic kinetic resolution is observed when an a-bromo- or a-acetylamino-/3-keto phosphate is subjected to the hydrogenation with an Ru-BINAP catalyst under suitable conditions. With RuC12[(A)-BINAP](DMF) (0.18 mM) as the catalyst, a racemic a-bromo-/3-keto phosphonate is hydrogenated at 25 °G under... 

In the hydrogenation of diketones by Ru-binap-type catalysts, the degree of anti-selectivity is different between a-diketones and / -diketones [Eqs (13) and (14)]. A variety of /1-diketones are reduced by Ru-atropisomeric diphosphine catalysts to indicate admirable anti-selectivity, and the enantiopurity of the obtained anti-diol is almost 100% (Table 21.17) [105, 106, 110-112]. In this two-step consecutive hydrogenation of diketones, the overall stereochemical outcome is determined by both the efficiency of the chirality transfer by the catalyst (catalyst-control) and the structure of the initially formed hydroxyketones having a stereogenic center (substrate-control). The hydrogenation of monohydrogenated product ((R)-hydroxy ketone) with the antipode catalyst ((S)-binap catalyst) (mis-... 

With an increase of conversion, the enantiopurity of unreacted (S)-substrate increases and the diastereoselectivity of the product decreases. Using Ru-((S)-binap)(OAc)2, unreacted (S)-substrate was obtained in more than 99% ee and a 49 1 mixture of anti-product (37% ee (2R,iR)) at 76% conversion with a higher kR ks ratio of 16 1 [46]. In the case of a racemic cyclic allyl alcohol 24, high enantiopurity of the unreacted alcohol was obtained using Ru-binap catalyst with a high kR ks ratio of more than 70 1 [Eq. (16)] [46]. In these two cases, the transition state structure is considered to be different since the sense of dia-stereoface selection with the (S)- or the (R)-catalysts is opposite if a similar OH/ C=C bond spatial relationship is assumed. 

Kinetic resolution results of ketone and imine derivatives are indicated in Table 21.19. In the kinetic resolution of cyclic ketones or keto esters, ruthenium atrop-isomeric diphosphine catalysts 25 induced high enantiomer-discriminating ability, and high enantiopurity is realized at near 50% conversion [116, 117]. In the case of a bicyclic keto ester, the presence of hydrogen chloride in methanol served to raise the enantiomer-discriminating ability of the Ru-binap catalyst (entry 1) [116]. 

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