Asymmetric hydrogenation kinetic studies

Both reactions were carried out under two-phase conditions with the help of an additional organic solvent (such as iPrOH). The catalyst could be reused with the same activity and enantioselectivity after decantation of the hydrogenation products. A more recent example, again by de Souza and Dupont, has been reported. They made a detailed study of the asymmetric hydrogenation of a-acetamidocin-namic acid and the kinetic resolution of methyl ( )-3-hydroxy-2-methylenebu-tanoate with chiral Rh(I) and Ru(II) complexes in [BMIM][BF4] and [BMIM][PFg] [55]. The authors described the remarkable effects of the molecular hydrogen concentration in the ionic catalyst layer on the conversion and enantioselectivity of these reactions. The solubility of hydrogen in [BMIM][BF4] was found to be almost four times higher than in [BMIM][PFg]. 

Based upon the above-mentioned assumptions, the reaction scheme in Figure 3.1 is reduced to the scheme shown in Figure 3.2A. It should be noted that active catalyst is used in the reaction scheme in Figure 3.1 while most asymmetric hydrogenation processes use a pre-catalyst (11). Hence, the relationship between the precatalyst and active catalyst needs to be established for the kinetic model. The precatalyst used in this study is [Et-Rh(DuPhos)(COD)]BF4 where COD is cyclooctadiene. The active catalyst (Xq) in Figure 3.2A is formed by removal of COD via hydrogenation, which is irreversible. We assume that the precatalyst is completely converted to the active catalyst Xq before the start of catalytic reaction. Hence, the kinetic model derived here does not include the formation of the active catalyst from precatalyst. 

We note that there are NMR-based kinetic studies on zirconocene-catalyzed pro-pene polymerization [32], Rh-catalyzed asymmetric hydrogenation of olefins [33], titanocene-catalyzed hydroboration of alkenes and alkynes [34], Pd-catalyzed olefin polymerizations [35], ethylene and CO copolymerization [36] and phosphine dissociation from a Ru-carbene metathesis catalyst [37], just to mention a few. 

The detailed pathways of asymmetric induction during catalysis are not well understood even for the more widely studied hydrogenations (8, 22), and matching substrates with the most suitable transition-metal chiral catalyst remains very much an empirical art. We are not aware of kinetic studies except our own on catalyzed asymmetric hydrogenations, although they usually are assumed to follow well-studied nonchiral analogs for example, RhClP3 systems, where... 

Dynamic Resolution of Chirally Labile Racemic Compounds. In ordinary kinetic resolution processes, however, the maximum yield of one enantiomer is 50%, and the ee value is affected by the extent of conversion. On the other hand, racemic compounds with a chirally labile stereogenic center may, under certain conditions, be converted to one major stereoisomer, for which the chemical yield may be 100% and the ee independent of conversion. As shown in Scheme 62, asymmetric hydrogenation of 2-substituted 3-oxo carboxylic esters provides the opportunity to produce one stereoisomer among four possible isomers in a diastereoselective and enantioselective manner. To accomplish this ideal second-order stereoselective synthesis, three conditions must be satisfied (1) racemization of the ketonic substrates must be sufficiently fast with respect to hydrogenation, (2) stereochemical control by chiral metal catalysts must be efficient, and (3) the C(2) stereogenic center must clearly differentiate between the syn and anti transition states. Systematic study has revealed that the efficiency of the dynamic kinetic resolution in the BINAP-Ru(H)-catalyzed hydrogenation is markedly influenced by the structures of the substrates and the reaction conditions, including choice of solvents. 

The mechanism of asymmetric hydrogenation of dehydroaminoacids has been studied by a combination of kinetic and spectroscopic methods, mainly by Halpern et al. [38] and Brown et al. [39]. It was proved that the substrate bound by both the double bond and the amide group. It was surprising to see that the major diastereomeric rhodium-alkene complex detected in solution was the less reactive one towards hydrogen. This showed the inaccuracy of previous models of the lock and key type between the prochiral double bond and the chiral... 

The real catalytic species 42 and key reactive intermediate 43 in asymmetric transfer hydrogenation with a chiral ligand 13-Ru(II) complex were isolated and characterized (Scheme 35) [120]. Examination of the reactivities of the two complexes as well as the kinetic study fully revealed the reaction mechanism. When the purple complex 42 is treated with 2-propanol at room temperature in the absence of any base, rapid elimination of acetone took place to produce the yellow Ru hydride species 43. The treatment of this 18-electron species 43 with... 

There are only two controlled kinetic studies of asymmetric hydrogenation, one of which was carried out using neutral diop complexes before the significance of ionization in polar solvents was fully appreciated, and, hence, the pathway studied is not necessarily the most efficient one. In the second, Halpern and Chan demonstrate that the kinetic form of the hydrogenation of methyl z-a-acetamidocinnamate catalyzed by the 1,2- /5(diphenylphosphino)-ethane rhodium cation in methanol is ... 

Some of the earliest mechanistic studies on homogeneous catalysis in organic solvents were reported by Halpem on the hydrogenation of olefins with Wilkmson s catalyst and on the mechanism of the asymmetric hydrogenation of dehydroamino acids by Knowles rhodium-DIPAMP system. Two important general conclusions were drawn from these stud-igg 19,20,66-69 gg noted in Chapter 14, the species in a catalytic system that accumulate in sufficient concentration to be identified spectroscopically may or may not lie directly on the catalytic cycle. In some cases, these species are connected to the catalytic cycle by equilibria, while in other cases they are unproductive species formed irreversibly. By associating particular complexes with the kinetic behavior of the catalytic reaction, one can assess whether the observed complex contributes positively or negatively to the rate of the catalytic process. 

However, based on structural, NMR, and kinetic studies, Halpern found that at room temperature the ratio of diastereoisomeric olefin-phosphine complexes does not influence the optical yield of the product. Formation of an excess of one of the enantiomeric reaction products depends on the rate of hydrogenation of olefin-phosphine complexes A and B. The rate of reaction of isomer A, which occurs in the reaction mixture in a considerably lesser amount, is so great that the main product is formed from this isomer. The mechanism of asymmetric hydrogenation of (Z)-PhCH = C(NHAc)COOEt may be represented by scheme (13.49). 

Mechanistic study of asymmetric hydrogenation showed that the reaction of the major isomer of the alkene-metal complex gave the minor isomer of the product. This paradox was resolved when it was found that the minor isomer reacts far faster with H2. A useful general point emerges from this work catalysis is a kinetic phenomenon and so the activity of a system may rely on a minor, even miniscule component of a catalyst. This emphasizes the danger on relying too much on spectroscopic methods in studying catalysts. The fact that a series of plausible intermediates can all be seen by, say, NMR in the catalytic mixtures does not mean these are the true intermediates. What we need to do is to show that each of the proposed intermediates react sufficiently fast to account for the formation of products, that is, that they are kinetically competent to do the reaction. 

Chen and Gerdes [69] performed a combination of ESI-MS and kinetic studies in the Pt"-catalyzed H/D exchange (Scheme 5.17) and Ir-basedhydrogenations [70]. Noyori used ESI( + )-MS to intercept the active species of the asymmetric hydrogenation reaction of acetophenone with chiral Ru-complex to give (R)-phenylethanol in 82% ee [71], Scheme 5.18. 

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