Stereoselective asymmetric hydrogenation

BINAP-Ru(II) halide complexes highly efficient catalysts for stereoselective asymmetric hydrogenation of a- and P-functionalized ketones. J. Org. Chem. 1994 59 3064-3076. 

SCHEME 30.18. Chemo- and stereoselective asymmetric hydrogenation of C=0 bonds conjugated with C=C linkages application to the syntheses of (ff)-carvone, (S)-a-damascone, and... 

Halpern J 1982 Mechanism and stereoselectivity of asymmetric hydrogenation Soienoe 217 401-7... 

Asymmetric hydrogenation has been achieved with dissolved Wilkinson type catalysts (A. J. Birch, 1976 D. Valentine, Jr., 1978 H.B. Kagan, 1978). The (R)- and (S)-[l,l -binaph-thalene]-2,2 -diylblsCdiphenylphosphine] (= binap ) complexes of ruthenium (A. Miyashita, 1980) and rhodium (A. Miyashita, 1984 R. Noyori, 1987) have been prepared as pure atrop-isomers and used for the stereoselective Noyori hydrogenation of a-(acylamino) acrylic acids and, more significantly, -keto carboxylic esters. In the latter reaction enantiomeric excesses of more than 99% are often achieved (see also M. Nakatsuka, 1990, p. 5586). 

Enantiomencally pure (+)- and (-)-diphenylethylenediamines have recently been used for highly stereoselective Dlels-Alder, aldol,8 allylation,9 osmylation,10 and epoxidafion11 reactions. Other synthetic applications involve enantioselective Michael addition12 and asymmetric hydrogenation.13... 

When a chiral ansa-type zirconocene/MAO system was used as the catalyst precursor for polymerization of 1,5-hexadiene, an main-chain optically active polymer (68% trans rings) was obtained84-86. The enantioselectivity for this cyclopolymerization can be explained by the fact that the same prochiral face of the olefins was selected by the chiral zirconium center (Eq. 12) [209-211]. Asymmetric hydrogenation, as well as C-C bond formation catalyzed by chiral ansa-metallocene 144, has recently been developed to achieve high enantioselectivity88-90. This parallels to the high stereoselectivity in the polymerization. 

In asymmetric hydrogenation, the pressure of hydrogen may have a substantial impact on both the rates and the stereoselectivities of the reaction. These effects may be attributed either to the formation of different catalytically competing species in solution or to the operation of kinetically distinct catalytic cycles at different pressures. 

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. 

Asymmetric hydrogenation of a,fi-unsa turated acids.1 2- Aryl-3-methyl-2-bu-tenoic acids (2) undergo highly stereoselective hydrogenation catalyzed by a complex of rhodium with the chiral (aminoalkyl)ferrocenylphosphine (1), but not with... 

The dynamic behavior of the model intermediate rhodium-phosphine 99, for the asymmetric hydrogenation of dimethyl itaconate by cationic rhodium complexes, has been studied by variable temperature NMR LSA [167]. The line shape analysis provides rates of exchange and activation parameters in favor of an intermo-lecular process, in agreement with the mechanism already described for bis(pho-sphinite) chelates by Brown and coworkers [168], These authors describe a dynamic behavior where two diastereoisomeric enamide complexes exchange via olefin dissociation, subsequent rotation about the N-C(olefinic) bond and recoordination. These studies provide insight into the electronic and steric factors that affect the activity and stereoselectivity for the asymmetric hydrogenation of amino acid precursors. 

Dehydropeptides (21) were employed for the asymmetric hydrogenation, catalyzed by chiral rhodium complexes of the hydroxyproline derivative (13). It was reported that the stereoselectivity is satisfying (ds = 90-95 %)50). 

R)-(—)-Pantolactone (22), a key intermediate for the preparation of the vitamin pantothenic acid, has been obtained with high stereoselectivity (e.e. = 87 %) by the asymmetric hydrogenation of the corresponding ketopantotyllactone in the presence of a rhodium complex of BPPM (13) 54). 

Nickel and other transition metal catalysts, when modified with a chiral compound such as (R,R)-tartaric acid 5S), become enantioselective. All attempts to modify solid surfaces with optically active substances have so far resulted in catalysts of only low stereoselectivity. This is due to the fact that too many active centers of different structures are present on the surface of the catalysts. Consequently, in asymmetric hydrogenations the technique of homogeneous catalysis is superior to heterogeneous catalysis56). However, some carbonyl compounds have been hydrogenated in the presence of tartaric-acid-supported nickel catalysts in up to 92% optical purity55 . 

If an asymmetric hydrogenation of C=C bonds is desired in the presence of achiral catalysts, chiral information is required to be present in the substrate. Peptides and cyclopeptides containing dehydroaminos acid units are very good substrates achieving quite high stereoselectivities upon asymmetric hydogenation on 10% Pd-C or other achiral catalysts 49 841. 

In the asymmetric hydrogenation of the (R)-phenylglycine derivative (54) in the presence of an achiral catalyst the stereoselectivity was reported 89) to be low. The lactone (55) could subsequently be converted into (S)-aspartic acid 89). This reaction sequence is an example of the intramolecular transfer of chirality with subsequent disappearance of the original chiral center. 

Asymmetric hydrogenation-based processes using a highly active and stereoselective catalyst generate relatively little waste. The asymmetric hydrogenation of readily preparable a-hydroxycarbonyl- or tz-alkoxycarbonyl-suInstituted enamrdes has frequently been applied to the preparation of unnatural a-amrno acids with a wide variety of side chains since the successful application of L-Dopa (Scheme 9.4) [13h]. 

P is an optically active tertiary phosphine, likely will resemble the RhCl(PPh3)3 system (23). However, even in this exhaustively studied system, both hydride and/or unsaturate routes are feasible (23, 24) by varying conditions, the choice of route could affect stereoselectivity. Most asymmetric hydrogenations have used prochiral olefinic acid substrates, and these systems have not been thoroughly studied even with nonchiral catalysts. 

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. 

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