Prochiral olefins, hydrogenation

The origin of the remarkable stereoselectivities displayed by chiral homogeneous catalysts has occasioned much interest and speculation. It has been generally assumed, using a lock-and-key concept, that the major product enantiomer arose from a rigid preferred initial binding of the prochiral olefin with the chiral catalyst. Halpren 48) on the basis of considerable evidence, reached the opposite conclusion the predominant product enantiomer arises from the minor, less stable diastereomer of the olefin-catalyst adduct, which frequently does not accumulate in sufficient concentration to be detected. The predominant adduct is in essence a dead-end complex for it hydrogenates at a much slower rate than does the minor adduct. 

In general, of the mixed phosphorus-thioether ligands that have been used in the asymmetric hydrogenation of prochiral olefins, the thioether-phosphinite ligands have provided some of the best results. As an example, a new class of thioether-phosphinite ligands developed by Evans et al. has recently proved to be very efficient for the rhodium-catalysed asymmetric hydrogenation of a... 

Several S/N ligands have also been investigated for the asymmetric hydrogenation of prochiral olefins. Thus, asymmetric enamide hydrogenations have been performed in the presence of S/N ligands and rhodium or ruthenium catalysts by Lemaire et al., giving enantioselectivities of up to 70% ee. Two... 

In addition, several S/S ligands were also investigated for the asymmetric hydrogenation of olefins. In 1977, James and McMillan reported the synthesis of various disulfoxide ligands, which were applied to the asymmetric ruthenium-catalysed hydrogenation of prochiral olefinic acid derivatives, such as itaconic acid. These ligands, depicted in Scheme 8.16, were active to provide... 

In recent years, the asymmetric hydrogenation of prochiral olefins have been developed in the presence of various chiral sulfur-containing ligands combined with rhodium, iridium or more rarely ruthenium catalysts. The best results have been obtained by using S/P ligands, with enantioselectivities of up to 99% ee in... 

The tetradentate ligands (340) and (341) form 1 1 metakligand complexes with [IrCl(cod)]2.548 The complexes were tested in the asymmetric hydrogenation of prochiral olefins, providing enantioselectivities up to 36%. The multitopic ligands L, (342) and (343), bind to Ir1 to form [IrL] species which have been characterized by elemental analysis, mass spectrometry, IR and NMR spectroscopy.549 The complexes show enantioselectivities of up to 30% for the hydrogenation of prochiral olefins under mild reaction conditions. 

The bis-DIOP complex HRh[(+)-DIOP]2 has been used under mild conditions for catalytic asymmetric hydrogenation of several prochiral olefinic carboxylic acids (273-275). Optical yields for reduction of N-acetamidoacrylic acid (56% ee) and atropic acid (37% ee) are much lower than those obtained using the mono-DIOP catalysts (10, II, 225). The rates in the bis-DIOP systems, however, are much slower, and the hydrogenations are complicated by slow formation of the cationic complex Rh(DIOP)2+ (271, 273, 274) through reaction of the starting hydride with protons from the substrate under H2 the cationic dihydride is maintained [cf. Eq. (25)] ... 

The development of chiral phosphorus ligands has made undoubtedly significant impact on the asymmetric hydrogenation. Transition metal catalysts with efficient chiral phosphorus ligands have enabled the synthesis of a variety of chiral products from prochiral olefins, ketones, and imines in a very efficient manner, and many practical hydrogenation processes have been exploited in industry for the synthesis of chiral drugs and fine chemicals. 

The catalytic asymmetric hydrogenation with cationic Rh(I)-complexes is one of the best-understood selection processes, the reaction sequence having been elucidated by Halpern, Landis and colleagues [21a, b], as well as by Brown et al. [55]. Diastereomeric substrate complexes are formed in pre-equilibria from the solvent complex, as the active species, and the prochiral olefin. They react in a series of elementary steps - oxidative addition of hydrogen, insertion, and reductive elimination - to yield the enantiomeric products (cf. Scheme 10.2) [56]. 

In this chapter, we review the growing family of phospholane-based chiral ligands, and specifically examine their applications in the field of enantioselective hydrogenation. In general, this ligand class has found its broadest applicability in the reduction of prochiral olefins and, to a significantly lesser extent, ketones and imines this is reflected in the composition of the chapter. Several analogous phosphacycle systems have also been included, where appropriate. 

Table 27.2 Asymmetric hydrogenation of other prochiral olefins. 

For details, see Koenig, K. E. Asymmetric Hydrogenation of Prochiral Olefins in Kosak, J. R. ed. Catalysis of Organic Reactions, Marcel Dekker, New York, 1984, Chap. 3. 

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. 

Effect of amphiphiles on the enantioselective hydrogenation of prochiral olefins in water... 

The maximum enantioselectivity of 18 % achieved so far in aqueous hydroformylations may not seem very promising. However, the history of asymmetric hydrogenation of prochiral olefins and ketones demonstrates that such a situation may change fast if there is a strong drive behind the case. 

These heterogeneous catalysts have shown excellent reactivity in the enantioselective hydrogenation of prochiral olefins with enantiomeric excess (ee s) > 92% and regioselectivities (>99%) with quantitative conversion. 

Asymmetric catalytic hydrogenation is unquestionably one of the most significant transformations for academic and industrial-scale synthesis. The development of tunable chiral phosphorous ligands, and of their ability to control enantioselectivity and reactivity, has allowed asymmetric catalytic hydrogenation to become a reaction of unparalleled versatility and synthetic utility. This is exemplified in the ability to prepare en-antiomerically enriched intermediates from prochiral olefins, ketones, and imines through asymmetric hydrogenation, which has been exploited in industry for the synthesis of enantiomerically enriched drugs and fine chemicals. 

An excellent review of the problems of the enantioselective heterocatalytic hydrogenation of prochiral double bonds, covering the literature up to 1970, has been compiled by Izumi57). Raney nickel catalysts modified with chiral amino acids or dipeptides gave only very moderate enantiomeric excesses of between 0 and 10% in the hydrogenation of olefins, carbonyl compounds or oximes 57). Only Raney nickel modified with (S)-tyrosine furnished a higher enantiomeric excess in the products58). 

Goncalves et have compared the amine (V) and the iminium salt (W) for the enantioselective epoxidation of some prochiral olefins in acetonitrile/water and found that the yields and ees are nearly the same for the epoxidation of a selection of olefins. The amines of type (X) are less well developed. Armstrong has summarized the developments in this field and suggested mechanisms based on hydrogen bonded species, one of which is shown in Figure 1.49. Typical yield and ee data for the epoxidation of 1-phenylcyclohexene for these catalysts are also shown in Figure 1.49. 

Enantioselective Hydrogenation of Prochiral Olefins - The presence of SDS increased both the rate and the enantioselectivity of hydrogenation of prochiral dehydroaminoacid derivatives using rhodium catalysts modified with the diphosphine 75a (Table 4) in aqueous media.500 For example, addition of 0.13 mmol of SDS to the Rh/75a catalyst shortened the reaction half time (tj/2) from... 

Hanson et a/.149 hydrogenated the prochiral olefin methyl a-acetamidocinna-mate using rhodium catalysts modified with the tenside chiral sulfonated diphosphine 34 (Table 2) in an ethylacetate/H20 micellar system at 25° C and 1 bar H2. The yield (100%) and enantiomeric excess (69%) were considerably higher than with the tetrasulfonated diphosphine 31 (Table 2 m=0, n=0) which gave 32% yield and 20% e.e. and the reaction time was shorter (1.5 versus 20h). Rh/34 and Rh/31 (m=0, n=0) gave nearly the same results (100% yield and 72-75% e.e. within < lh) in homogeneous methanol solutions.149... 

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