Combination of asymmetric hydrogenation

Combination of Asymmetric Hydrogenation with Enzymatic Hydrolysis 401... 

The approach can be coupled with other methods to prepare amino acids, such as to access [3-substituted a-amino acids. The methodology gives a way to prepare all four possible isomers of (3-aryl a-amino acids by a combination of asymmetric hydrogenation and the use of the deracem-ization process to invert the a-center (Scheme 9.36)." "°... 

The solvent employed in asymmetric catalytic reactions may also have a dramatic influence on the reaction rate as well as the enantioselectivity, possibly because the solvent molecule is also involved in the catalytic cycle. Furthermore, the reaction temperature also has a profound influence on stereoselectivity. The goal of asymmetric hydrogenation or transfer hydrogenation studies is to find an optimal condition with a combination of chiral ligand, counterion, metal, solvent, hydrogen pressure, and reaction temperature under which the reactivity and the stereoselectivity of the reaction will be jointly maximized. 

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... 

FIGURE 5. Symmetry-adapted combinations of two Is hydrogen AOs (labelled symmetric or asymmetric with respect to the plane perpendicular to the HSH plane) and of the p orbitals of oxygens, where the labels are with respect to planes CSC and... 

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 use of rhodium catalysts for the synthesis of a-amino acids by asymmetric hydrogenation of V-acyl dehydro amino acids, frequently in combination with the use of a biocatalyst to upgrade the enantioselectivity and cleave the acyl group which acts as a secondary binding site for the catalyst, has been well-documented. While DuPhos and BPE derived catalysts are suitable for a broad array of dehydroamino acid substrates, a particular challenge posed by a hydrogenation approach to 3,3-diphenylalanine is that the olefin substrate is tetra-substituted and therefore would be expected to have a much lower activity compared to substrates which have been previously examined. 

The asymmetric organosilane reduction of prochiral ketones has been studied as an alternative to the asymmetric hydrogenation approach. A wide variety of chiral ligand systems in combination with transition metals can be employed for this purpose. The majority of these result in good to excellent chemical yields of the corresponding alcohols along with a trend for better ee results with aryl alkyl ketones than with prochiral dialkyl ketones. 

The Rh(I)/136 or Rh(I)/137 combination can be used in the asymmetric hydrogenation of 1-arylenamides in 90-99% ee, with Rh(I)/137 being the better of the two.676 Me-DuPHOS and related ligands with rhodium reduce 1-aryl-2-alkylenamides in >90% ee677 whereas the Rh(I)/DIOP combination carries this out in 97.3-99% ee selectivity.678 Finally, the Rh(I)/138 system reduces /3-substituted-a-arylenamides in 95-99% ee, and a-substituted acetamidoethylenes in 75.7-90% ee.674... 

Reetz and Goossen et al. reported recently the asymmetric hydrogenation of a series of enol esters using monodentate phosphite ligands 17 and 24 based on a combination of BINOL and carbohydrates or simple alcohols the results of these studies are shown in Table 28.6. 

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