Homogeneous asymmetric hydrogenation reactions

Homogeneous asymmetric hydrogenation reactions have been studied intensively with amino acid precursors in aqueous micellar solutions. In early work only stabilising effects of added amphiphiles were observed [53, 54]. However, for the hydrogenation of Z-a-acetamidocinnamic acid methyl ester (Fig. 5.10) with an optically active rhodium-phosphane complex (Fig. 5.11) in the presence of micelles a significant increase in activity and enantioselectivity was found in comparison to reaction in pure water [55]. 

Process Evaluation and Improvement. As homogeneous asymmetric hydrogenation processes are scaled up, one major concern is cost because the catalyst is usually expensive. Hence, several criteria for a commercially viable process (2), including selectively, conversion, catalyst loading (S/C, the molar ratio of substrate to catalyst), reaction time, and TOF (turnover frequency, the ratio of catalyst loading to reaction time), should be considered to evaluate the process and provide a guide for improvement. 

Homogeneous asymmetric hydrogenation is a practical synthetic method (27). The DIPAMP-Rh-catalyzed reaction has been used for the commercial production of (S)-DOPA [(5)-3-(3,4-dihydroxy-phenyl) alanine] used to treat Parkinson s disease (Monsanto Co. and VES Isis-Chemie) (Scheme 12) (27, 28). (S)-Phenylalanine, a component of the nonnutritive sweetener aspartame, is also prepared by en-antioselective hydrogenation (Anic S.p.A. and Enichem Synthesis) (29). A cationic PNNP-Rh(nbd) complex appears to be the best catalyst for this purpose (15c) (see Scheme 5 in Chapter 1). 

Historically, reaction of simple olefins in the presence of chiral phosphine-Rh complexes in 1968 marked the first examples of homogeneous asymmetric hydrogenation [6], However, only a few successful results have been reported for asymmetric hydrogenation of unfunctionalized olefins. Some examples with late and early transition-metal complexes are illustrated in Schemes 1.27-28 and Schemes 1.29-30, respectively. 

If some of the ligands bonded to the metal atom in a homogeneous catalyst are chiral, then the hydrogenation can, in theory, produce an excess of one enantiomer of the reduction product. One catalyst that has been found to be effective in such an asymmetric hydrogenation reaction is this chiral rhodium complex ... 

In recent years the synthesis of chiral and achiral tripodal phosphines and their application in homogeneous catalysis has been studied in more detail [2]. Enantiomerically pure tripodal ligands were synthesized from the corresponding trichloro compounds and chiral, cyclic lithio-phosphanes, e.g. 17, (Scheme 6) [21,22], Using a rhodium(I) complex of ligand 18, an enantiomeric excess of 89 % was obtained in the asymmetric hydrogenation reaction of methyl acetami-docinnamate (19). 

Dendrimer based-BINAP polymers have been prepared from 124. A series of soluble dendritic mono-BINAP ligands with Frechet-type polyether wedges like 127 and dendritic poly-BlNAP ligands like 128 have been reported Ruthenium complexes of both classes of dendrimer were prepared and found to be comparable both in catalytic activity and enatioselectivity as homogeneous BINAP analogs in asymmetric hydrogenation reactions. 

Apart from the structure of the chiral phosphine, optical selectivity of homogeneous asymmetric hydrogenation of ketones is strongly influenced by other reaction parameters, such as temperature, pressure, the P/Rh mole ratio with in situ prepared systems, " the quality and quantity of other additives, and the solvent, etc. While the effect of the latter is shown in Table 3, the influence of EtsN on enantioselectivity in different sol-vents " is demonstrated in Figure 10.4. By increasing the EtsN/Rh mole ratio in methanol, there is a maximum in enantioselectivity (ascribed to a HRh(P-P) type catalyst), but further amounts of the base decrease the optical purity of the secondary alcohol considerably. This may be explained... 

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.

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