Asymmetric hydrogenation methyl cinnamate

Ruthenium complexes of (129) and (130)336 were investigated for the asymmetric hydrogenation of prochiral 2-R-propenoic acids (Scheme 62a) rhodium complexes of these ligands were used for hydrogenation of acetoamido-cinnamic acid methyl ester (Scheme 62c) and hydrogenation of acetophenone-benzylamine (Scheme 62b). The results obtained with these... 

Table 1 Asymmetric hydrogenation of (Z)-2-(acetamido) cinnamic acid, 2-(acetamido) acrylic acid and their methyl esters...

In asymmetric hydrogenation of olefins, the overwhelming majority of the papers and patents deal with hydrogenation of enamides or other appropriately substituted prochiral olefins. The reason is very simple hydrogenation of olefins with no coordination ability other than provided by the C=C double bond, usually gives racemic products. This is a common observation both in non-aqueous and aqueous systems. The most frequently used substrates are shown in Scheme 3.6. These are the same compounds which are used for similar studies in organic solvents salts and esters of Z-a-acetamido-cinnamic, a-acetamidoacrylic and itaconic (methylenesuccinic) acids, and related prochiral substrates. The free acids and the methyl esters usually show appreciable solubility in water only at higher temperatures, while in most cases the alkali metal salts are well soluble. 

The product could be quantitatively separated and the recovered IL catalyst solution recycled several times without any significant change in activity or selectivity. The RTIL [emim][OTf] was employed as the sole reaction solvent for the asymmetric hydrogenation of methyl a-benzamido cinnamate. Near-quantitative conversions were observed At 60 psi hydrogen partial pressure and 50 °C for 24 h, using both the achiral DiPFc-Rh and the chiral EtDuPHOS-Rh catalysts.Enantiomeric excess of 89% was observed for hydrogenations carried out with the chiral catalyst. 

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. 

Fig. 3 Conversion curves for the asymmetric hydrogenation of Z-methyl-a-acetamido-cinnamate for the different catalyst generations...

Recently, Reek et al. published the synthesis of a 9H,9 H- [4,4 ]bicarbazole-3,3r-diol (BICOL)-based chiral monodentate phosphoramidite ligand, which was functionalized with two different third-generation carbosilane dendritic wedges (Fig. 26) [57]. As reference reaction in the catalytic study, the rhodium-catalyzed asymmetric hydrogenation of Z-methyl-a-acetamido-cinnamate was chosen. Using a ligand-to-rhodium ratio of 2.2 led to enantio-selectivities which were comparable to the results obtained using the parent BINOL-derived monodentate phosphoramidite MonoPhos. 

Amphiphilic diblock copolymers based on 2-oxazoline derivatives with chiral diphosphine 187 were prepared (Scheme 3.61) and used in the asymmetric hydrogenation of methyl (Z)-(z-acelarnido cinnamate 188 in water to give the (R)-phenylalanine derivative 189 in 85% ee [124]. The polymeric catalyst could be recycled. This result illustrated the advantages of using amphiphihc copolymers for the efficient transformation of a hydrophobic substrate in water. 

In another example de Souza and Dupont studied the asymmetric hydrogenation of a-acetamido cinnamic acid and the kinetic resolution of ( )-methyl-3-hydroxy-2-methylenebutanoate with chiral Rh(I) and Ru(ii) complexes in [BMIM][BF4] and [BMIM][PFs] [106]. A special focus oftheir work was on the influence of H2 pressure on conversion. They determined the hydrogen solubility in the ionic liquid using... 

Biemer et al. reported the enantioselective behaviors of a Pd catalysts supported on specially prepared silica gels, which have been precipitated from Na silicate wiA HCl in the presence of optically active alkaloids sulfates of quinine (Q), quinidine (Qd ), cinchonine (Cn), or cinchonidine (Cnd). These catalysts proved to be active in the asymmetric hydrogenation of 2-methyl-cinnamic acid (Scheme 3.1.) . 

In the asymmetric hydrogenation of the methyl ester of a-acetamido cinnamic acid, 3.24 cannot be observed by conventional NMR techniques. In situ PHIP-NMR studies in contrast do show two hydride signals at -19 and -2 ppm. Using a C-enriched substrate, the coupling between the asterisk-labeled carbon and the hydride at -2 ppm can also be observed. Based on the NMR data, the actual structure is concluded to be more like 3.25 than 3.24. 

As mentioned earlier, in the asymmetric hydrogenation of methyl a-acetamido cinnamate, in situ PHIP-NMR data suggest structure 335 for the dihydride intermediate. Computational energy calculations based on density functional theory (DFT) are also in agreement with such a structure. In this case, to keep the computational requirements to a manageable level, calculations were carried out on a model complex where PHANEPHOS was approximated by two PH3 ligands. 

The cationic Rh(I) complex was further applied in the asymmetric hydrogenation of dimethyl itaconate and methyl 2-(A -acetylamino)cinnamate, showing turnover frequencies of up to 2500 h and enantioselectivities of up to 79% of... 

In 2001, Engel and Gade [57] prepared a series of chiral phosphine-functionalized poly(propyleneimine) (PPI) dendrimers (29) by the reaction of carboxyl-linked C2-chiral pyrphos ligand (pyrphos, 3,4-bis(diphenylphosphino) pyrrolidine) with commercially available zero- to fourth-generation PPI. The subsequent metallation of multisite phosphines with [Rh(COD)2]-BF4 (COD, 1,5-cyclooctadiene) was in situ generated and carried out in the asymmetric hydrogenation of Z-methyl-a-acetamido cinnamate and dimethyl itaconate (Figure 4.28, Equation 1). In contrast... 

As one of the enzymic reactions, asymmetric synthesis catalyzed by cyclodextrins has been studied in the past, but gave all the products in a low optical yield. We have already found a strong chiral induction for the chlorination of methacrylic acid in the crystalline cyclodextrin complexes. 100 % enantiomeric excess (e.e.) of (-)-2,3-dichloro-2-methyl-propionic acid and 88 % e.e. of its enantiomer were isolated in a- and 3-cyclodextrins, respectively. This paper describes asymmetric addition of gaseous halogens and hydrogen halides in the crystalline complexes comprising trans-cinnamic acid as a reactant and a- or 3-cyclodextrin as chiral matrix. Asymmetric bromination of menthyl cinnamate and of salts from the acid and several chiral amines have been reported, but gave low chiral inductions up to 2 16 % e.e.. 

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