Asymmetric Hydrogenation of Prochiral Olefins

The use of soluble rhodium catalysts containing chiral ligands to obtain high stereoselectivity in the asymmetric hydrogenation of prochiral olefins represents one of the most important achievements in catalytic selectivity, rivaling the stereoselectivity of enzyme catalysts [J. Halpem, Science, 217 (1982) 401]. Many chiral ligands 

Hydrogenation of MAC catalyzed by a homogeneous Rh catalyst to give R and S enantiomers of N-acetylphenylalanine methyl ester. 

N-acetylphenylalanine methyl ester during MAC hydrogenation in methanol solvent [C. R. Landis and J. Halpern, J. Am. Chem. Soc., 109 (1987) 1746]. The DI-PAMP coordinates to the rhodium through the phosphorus atoms and leaves plenty of space around the Rh cation for other molecules to bind and react. The unique feature of this system is that the chirality of the DIPAMP ligand induces the high stereoselectivity of the product molecules. An analogous nonchiral ligand on the Rh cation produces a catalyst that is not enantioselective. 

Expressions for relative concentrations of the intermediates and products are developed from concepts discussed in earlier chapters, namely, the use of a total catalytic site balance and the application of the steady-state approximation. The total amount of rhodium catalyst in the reactor is considered constant, [ ]q, so that the site balance becomes  

The steady-state approximation indicates that the concentrations of reactive intermediates remain constant with time. In other words, the net rate of MAC binding to the catalyst to form an intermediate must be the same as the rate of hydrogenation (or disappearance) of the intermediate. The steady-state approximation for the coupled catalytic cycles is expressed mathematically as  

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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 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. 

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. 

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. 

In the late sixties, several research groups in the U.S. (6), Europe (7), and Japan (8) initiated studies of homogeneous catalytic asymmetric syntheses. Of these efforts, the catalytic asymmetric hydrogenation of prochiral olefins reported by Knowles, et al. (6,9) attracted most attention. The importance of this technology was shown by its application in the Monsanto L-DOPA process which had since become an industrial flagship in catalytic asymmetric syntheses (Figure 1). 

Using these sugar-based ligands, the Zheng/Chen group has explored a variety of asymmetric hydrogenation of prochiral olefins. Three types of hydrogenation examined are... 

Most recently, these BlNAP-cored dendrimers were further employed in the Ir-catalyzed asymmetric hydrogenation of quinolines by Fan et al. (Scheme 4.3) [33]. Unlike the asymmetric hydrogenation of prochiral olefins, ketones and imines, the hydrogenation of heteroaroniatic compounds proved to be rather difficult [34—37]. All four generations of dendrimer catalysts generated in situ from BlNAP-cored dendrimers and [lr(COD)Cl]2 were found to be effective, even at an extremely high substrate catalyst ratio in the asymmetric hydrogenation of quinaldine with... 

The successful industrial application of the homogeneous catalytic asymmetric hydrogenation of prochiral olefins depends on the ability of the catalyst systems to offer high activity both in terms of reaction rate and efficient utilization of the catalyst (as the molar substrate to catalyst ratio S/C). It is also essential for the reaction to deliver the product with high enantiomeric excess and in good yield under conditions appropriate for industrial manufacture. In addition, the catalysts should be accessible in appropriate quantities for commercial manufacture. 

It should be finally noted that hydroxyphosphines can be converted under very smooth conditions into sulfonated phosphines by acylation with o-sulfobenzoic anhydride, as shown by Borner et al. (Eq. 5) [26]. With this methodology in hand the severe conditions commonly used for the incorporation of sulphonate groups in phosphines can be avoided. Acid-labile functional groups like acetals survive under these conditions. In comparison to the parent hydroxyphosphines the water solubility of the relevant Rh catalysts was strongly enhanced [27]. In the asymmetric hydrogenation of prochiral olefins, moderate enantioselectivities were achieved. 

In comparison to the parent hydroxyphosphines the water solubility of the relevant Rh catalysts was strongly enhanced [23]. In the asymmetric hydrogenation of prochiral olefins, moderate enantioselectivities were achieved. 

Asymmetric Hydrogenation of Prochiral Olefins by Rhodium-DuPhos Catalysts... 

In the DIPAMP diphosphine, the two phosphorus atoms themselves are optically active. Rhodium DIPAMP complexes, discovered by Knowles (recipient of the Nobel Prize in 2001) (120,121), have been used by Monsanto for the commercial synthesis of (S)-3-(3,4-dihydroxyphenyl)alanine,(S)-DOPA, extensively used for the treatment of Parkinson s disease. Cationic rhodium complexes with these chiral diphosphines are very effective for the asymmetric hydrogenation of prochiral olefins, such as the interesting a-acetamidoacrylates, which can bind... 

The sugar phosphines (431) and (432) have been prepared and used as ligands for Wilkinson s catalysts in the asymmetric hydrogenation of prochiral olefins. ... 

By employing a chiral diphosphine such as (R,R)-l,2-bis (o-methoxy-phenyl)phenylphosphino ethane ((R,R)-DIPAMP, 11), (S,S)-2,3-bis(di-phenylphosphino)butane ((S,S)-CHIRAPHOS, 12), and (R,R)-rranj-4,5-bis(diphenylphosphinomethyl)-2,2-dimethyldioxolan ((R,R)-DIOP, 13) as a chelating ligand in catalyst 7, asymmetric hydrogenation of prochiral olefinic substrates such as a-acylaminocinnamates has become possible. 

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