Asymmetric hydrogenation of Dimethyl itaconate

The catalyst was made in situ by mixing phosphinite (8.6 mg, 0.011 mmol) with [Rh(cod)2]BE4 (4.1 mg, O.Olmmol) in 10mL of CH2CI2 under argon. The solution was stirred for 15 min and then the substrate was added. The mixture was transferred into the autoclave under an argon atmosphere. 

The autoclave was pressurized with H2 and then shaken at a frequency of 180min, 75° from the upright position, with horizontal amphtude of 3 cm. The reaction was monitored by the change in pressure. 

The reaction mixture was analyzed by gas chromatography (GC) and was distilled under vacuum (1 mmHg) to remove the catalyst. The enantiomeric excess of the distilled product was determined by GC analysis. 

Entry Substrate Reaction time (min) Pressure (atm) Conversion (%) ee (configuration) (%) 

General conditions substrate catalyst = 500, room temperature, 2 mmol of B was used. 

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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). 

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

If Q-symmetric ligands are employed in asymmetric hydrogenation instead of the corresponding C2-symmetric ligands, there coexist principally four stereoiso-meric substrate complexes, namely two pairs of each diastereomeric substrate complex. Furthermore, it has been shown that, for particular catalytic systems, intramolecular exchange processes between the diastereomeric substrate complexes should in principle be taken into account [57]. Finally, the possibility of non-estab-hshed pre-equilibria must be considered [58]. The consideration of four intermediates, with possible intramolecular equilibria and disturbed pre-equihbria, results in the reaction sequence shown in Scheme 10.3. This is an example of the asymmetric hydrogenation of dimethyl itaconate with a Rh-complex, which contains a Q-symmetrical aminophosphine phosphinite as the chiral ligand. 

The hydrogen consumption and enantioselectivities for the asymmetric hydrogenation of dimethyl itaconate with various substituted catalysts of the basic type [Rh(PROPRAPHOS)COD]BF4 are illustrated in Figure 10.13 [61]. The systems are especially suitable for kinetic measurements because of the rapid hydrogenation of COD in the precatalyst. There are, in practice, no disturbances due to the occurrence of induction periods. 

Table 10.2 Kinetic analysis of the asymmetric hydrogenation of dimethyl itaconate with derivatives of [Rh(PROPRAPHOS)-COD]BF4 (see Fig. 10.13).

Fig. 10.17 Asymmetric hydrogenation of dimethyl itaconate with [Rh(Ph-j8-glup-OH)(MeOH)2]BF4 comparison between first-order fit (x-axis) and experimental values. Conditions 0.01 mmol catalyst 1.0 mmol substrate 15.0 mL MeOH 1.013 bar total pressure.

An unusual carbene-thioether hybrid ligand 174 was synthesized and applied in the rhodium-catalyzed asymmetric hydrogenation of dimethyl itaconate by Chung and co-workers however, the selectivity and activity were low (Table 27.7, entry 34) [135]. 

When a commercially available C2-symmetric l,4 3,6-dianhydro-D-mannite 29 is chosen as the backbone, reaction of this diol compound with chlorophos-phoric acid diaryl ester gives a series of phosphorate ligands 30. These were tested using the asymmetric hydrogenation of dimethyl itaconate as a model... 

The dynamic behavior of the model intermediate rhodium-phosphine 99, for the asymmetric hydrogenation of dimethyl itaconate by cationic rhodium complexes, has been studied by variable temperature NMR LSA [167]. The line shape analysis provides rates of exchange and activation parameters in favor of an intermo-lecular process, in agreement with the mechanism already described for bis(pho-sphinite) chelates by Brown and coworkers [168], These authors describe a dynamic behavior where two diastereoisomeric enamide complexes exchange via olefin dissociation, subsequent rotation about the N-C(olefinic) bond and recoordination. These studies provide insight into the electronic and steric factors that affect the activity and stereoselectivity for the asymmetric hydrogenation of amino acid precursors. 

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... 

Table 2.1 Asymmetric hydrogenation of dimethyl itaconate (A) and methyl (Z)-ot-acetamido cinnamate (B)...

Asymmetric hydrogenation of dimethyl itaconate and methyl (Z)-a-acetamido cinnamate with in situ formed rhodium(I)-diphosphinite catalyst system gave the desired products with high activity and enantioselectivity (Table 2.1). The asymmetric hydrogenation may be applied to a wide range of substrates. 

Figure 8.12 U rea functionalized phosphate ligands for asymmetric hydrogenation of dimethyl itaconate (DMI), N-(3,4-dihydronaphthalen-2-yl)acetamide (DNA) and methyl 2-acetamidoacrylate (MAA).

Rhodium-Catalyzed Asymmetric Hydrogenation of Dimethyl Itaconate 11 Using Biphenyl-Based Phosphite Ligands3... 

The asymmetric hydrogenation of dimethyl itaconate catalyzed by Ru-complexes of 21 and 23 in MeOH as a solvent was reported by Stuart and coworkers [48]. As... 

Table 7.16 Catalytic asymmetric hydrogenation of dimethyl itaconate using chiral perfluoronated phosphorus ligands in scCO,.

Ferrocene dendrimers are also of interest for reasons other than their redox activity. For example, metalloden-drimer 242 possesses planar chiral ferrocene units that make the bidentate phosphine ligation sites of potential interest for applications in asymmetric catalysis. Indeed, asymmetric hydrogenations of dimethyl itaconate catalyzed by Rh complexes of 242 showed impressive ee values of 98%. " ... 

Stuart and co-workers reported the first synthesis of a light fluorous BINAP, (R)-6,6 -bis(lH,lH,2H,2H-perfluorooctyl)-2,2 -bis(diphenylphosphino)-l,l -bi-naphthyl (F content = 38%), and its application to a Ru complex catalyzed asymmetric hydrogenation of dimethyl itaconate [Eq. (2)] [10). The reaction was carried out at ambient temperature under the same reaction conditions as those reported by Noyori [11). The chemical yield (83%) and enantioselectivity (95.7% ee) were similar to those reported (88% and 95.4% ee, respectively). However, there was no description of the recovery of the catalyst or ligand. 

Hydrogenations to produce enantiomerically pure compounds are particularly interesting for pharmaceutical and fine chemicals production. Stephenson and co-workers (102,103) have examined the continuous asymmetric hydrogenation of dimethyl itaconate using a supported chiral Rh catalyst in SCCO2. The process occurs under mild conditions with minimal catalyst leaching and can achieve high enantiomeric excess (83%) of the desired product. 

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