Chiral hydrogeneation catalysts

Catalytic asymmetric hydrogenation was one of the first enantioselective synthetic methods used industrially (82). 2,2 -Bis(diarylphosphino)-l,l -binaphthyl (BINAP) is a chiral ligand which possesses a Cg plane of symmetry (Fig. 9). Steric interactions prevent interconversion of the (R)- and (3)-BINAP. Coordination of BINAP with a transition metal such as mthenium or rhodium produces a chiral hydrogenation catalyst capable of inducing a high degree of enantiofacial selectivity (83). Naproxen (41) is produced in 97% ee by... 

William Knowles at the Monsanto Company discovered some years ago that u-amino acids can be prepared enantioselectively by hydrogenation of a Z enam-ido acid with a chiral hydrogenation catalyst. (S)-Phenylalanine, for instance, is prepared in 98.7% purity contaminated by only 1.3% of the (H) enantiomer when a chiral rhodium catalyst is used. For this discovery, Knowles shared the 2001 Nobel Prize in chemistry. 

Amino acids can be synthesized in racemic form by several methods, including ammonolysis of an a-bromo acid, alkylation of diethyl acetamido-malonate, and reductive amination of an cv-keto acid. Alternatively, an enantio-selective synthesis of amino acids can be carried out using a chiral hydrogenation catalyst. 

An example of the use of PGSE NMR spectroscopy can be found in the studies of Selke et al. [33], who investigated the dependence of enantioselectivity on the distribution of a chiral hydrogenation catalyst between aqueous and micellar phases. When a compound is incorporated into a micelle, its mobility is much lower compared to its mobility in solution. This effect is exactly what is probed with PGSE NMR. The calculated diffusion coefficient is a time-averaged value of the lower diffusion coefficient of the catalyst incorporated into the micelles, and of the diffusion coefficient of the free catalyst. An increased amount of micelle-embedded catalyst was found to lead to an increased enantioselectivity. 

The development of chiral hydrogenation catalysts for unfunctionalized alkenes also allows enantioselective hydrogenation of functionalized olefins where the functionality in the molecule is remote from the double bond. A series of oxazoline-, imidazoline- and pyridine-derived catalysts have been screened for the hydrogenation of unsaturated derivatives of vitamin E (Scheme 30.3). Hy-... 

In the meantime, a rather large and multifaceted number of chiral hydrogenation catalysts based on rhodium have entered the chemical literature. In Figure... 

Chiral hydrogenation catalysts. Rhodium and ruthenium phosphines are effective homogeneous catalysts for hydrogenation. Chiral ligands can be attached to accomplish asymmetric induction, the creation of a new asymmetric carbon as mostly one enantiomer. 

Enantiopure alcohols can be produced using chiral hydrogenation catalysts for the reduction of ketones. A major breakthrough in this area was achieved in the mid-1980s by Takaya and Noyori, following the initial work of Ikariya s group... 

Knowles amino acid synthesis (Section 26.3) an enantioselective method of amino acid synthesis by hydrogenation of a Z enamido acid with a chiral hydrogenation catalyst. 

Investigation of heterogeneous chiral hydrogenation catalysts started in the late fifties in Japan and has seen a renaissance in the last few years [2,4,6]. In spite of many efforts, only two classes of modified catalyst systems have been found that are of synthetic use at this time nickel catalysts modified with tartaric acid... 

Pore size, effect on isomerisation 25-P-08 Pt/MCM-41 chiral hydrogenation catalyst 23-P-25 ... 

Attempts to improve the solubility and immobilization of chiral hydrogenation catalysts in ionic liquids were presented by Lee and coworkers [112]. They synthesized a chiral Rh-complex carrying the dicationic bisphosphine ligand depicted in Fig. 5.3-7. Immobilization of the tricationic complex in [BMIM][SbFe] showed better immobilization results in contact with iPrOH compared to the non-modified complex Me-BDPMI in the Rh-catalyzed asymmetric hydrogenation of N-acetylphenylethenamine (Scheme 5.3-11). The ionic catalyst solution was reused three times without loss of activity. In the fourth mn conversion decreased but high conversions could still be realized by increasing the reaction time. 

Titanium complexes with asymmetrically substituted cyclopentadienyl ligands can be used as chiral hydrogenation catalysts. The complexes [LfTiCl2] (L = 15,16) were prepared. A [(15)2(TiCl2]/BuLi catalyst under 1 atm H2 reduces 2-phenylbut-l-ene in up to 33% ee. The hydrogenation was used as a test reaction to measure the asymmetric induction achieved by the new ligands. ... 

Within the last three decades, chemists have discovered ways to embed transition metal hydrogenation catalysts in chiral molecules with the result that hydrogen can be delivered to only one face of the alkene. In catalytic reductions where a new chiral center is formed, a large enantiomeric excess of one enantiomer may be formed, and the reaction is said to be enantioselective. The most widely used of these chiral hydrogenation catalysts involve the chiral ligand... 

Enantioseiective Reduction (Section 6.7) The most useful chiral hydrogenation catalysts involve a chiral phosphorus-containing ligand complexed with either ruthenium or rhodium. 

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