Asymmetric hydrogenation oximes

Catalytic asymmetric hydrogenation is a relatively developed process compared to other asymmetric processes practised today. Efforts in this direction have already been made. The first report in this respect is the use of Pd on natural silk for hydrogenating oximes and oxazolones with optical yields of about 36%. Izumi and Sachtler have shown that a Ni catalyst modified with (i ,.R)-tartaric acid can be used for the hydrogenation of methylacetoacetate to methyl-3-hydroxybutyrate. The group of Orito in Japan (1979) and Blaser and co-workers at Ciba-Geigy (1988) have reported the use of a cinchona alkaloid modified Pt/AlaO.i catalyst for the enantioselective hydrogenation of a-keto-esters such as methylpyruvate and ethylpyruvate to optically active (/f)-methylacetate and (7 )-ethylacetate. 

Keywords Asymmetric hydrogenation, Asymmetric transfer hydrogenation, Ketimines, Oxime, Nitrones... 

Asymmetric hydrogenation offers a useful synthetic route to chiral amines. Although the mechanism is unknown, only the (7%/V-acetyl-1 -arvlalkylamine 21 with 95% ee was obtained by the hydrogenation of a mixture of ( )- and (Z)-enamides 20a and 20b using Rh-Me-DuPHOS (XI). The A-acetvl enamines 20a,b are prepared by the reduction of oximes with Fe powder in acetic anhydride [21]. Also the acetamide 23 was obtained from 22 [22]. 

Comparatively with these metals, ruthenium is less investigated, even some data about the asymmetric hydrogenation of oximes, allytic alcohols or p-keto esters using BINAP, DIOP or BIPHEM... 

While several general methods for the asymmetric hydrogenation of C=0 bonds have been developed, to generalize the methods for the enantioselective hydrogenation of pro-chiral compounds with C=N double bonds as imines, oximes, or hydrazones, and so on, to the corresponding chiral amines is still a challenging task, and this is mostly because of the following reasons ... 

Asymmetric catalytic reduction reactions represent one of the most efficient and convenient methods to prepare a wide range of enantiomerically pure compounds (i.e. a-amino acids can be prepared from a-enamides, alcohols from ketones and amines from oximes or imines). The chirality transfer can be accomplished by different types of chiral catalysts metallic catalysts are very efficient for the hydrogenation of olefins, some ketones and oximes, while nonmetallic catalysts provide a complementary method for ketone and oxime hydrogenation. 

Organometallic compounds asymmetric catalysis, 11, 255 chiral auxiliaries, 266 enantioselectivity, 255 see also specific compounds Organozinc chemistry, 260 amino alcohols, 261, 355 chirality amplification, 273 efficiency origins, 273 ligand acceleration, 260 molecular structures, 276 reaction mechanism, 269 transition state models, 264 turnover-limiting step, 271 Orthohydroxylation, naphthol, 230 Osmium, olefin dihydroxylation, 150 Oxametallacycle intermediates, 150, 152 Oxazaborolidines, 134 Oxazoline, 356 Oxidation amines, 155 olefins, 137, 150 reduction, 5 sulfides, 155 Oxidative addition, 5 amine isomerization, 111 hydrogen molecule, 16 Oxidative dimerization, chiral phenols, 287 Oximes, borane reduction, 135 Oxindole alkylation, 338 Oxiranes, enantioselective synthesis, 137, 289, 326, 333, 349, 361 Oxonium polymerization, 332 Oxo process, 162 Oxovanadium complexes, 220 Oxygenation, C—H bonds, 149... 

Numerous asymmetric catalytic hydrogenations of carbon-nitrogen double bonds have been carried out. Some of the substrates used are oximes and hydrazones, but most of the reactions were carried out using Schiff s bases of ketones. a-Keto acids are precursors of a-amino acids in biosynthesis, and therefore a-keto acids have been used for the asymmetric syntheses of a-amino acids. ... 

There are some reports on the asymmetric catalytic hydrogenation of C=N double bonds. Rhodium phosphine complexes do not have high activity, and the stereoselectivity is low. - Homogeneous hydrogenation of oximes, Schiff s bases and cyclic imines " have been reported. A cyano cobalt complex has been used for the homogeneous catalytic hydrogenation of oximes and Schiff s bases but the degree of asymmetric induction is unknown. 

Halpem [8] described the reaction of cyclic ketones containing an asymmetric carbon a to the carbonyl function with (- -)-2,2,2-trifluoro-l-phenylethylhydra-zine (47) (see Section 4.4.2 for structures of numbered reagents) to form diastereomeric hydrazones, which were resolved by GC. However, some racemization was noted and it was recommended that the reaction should not be considered for ketones containing a hydrogen a to the asymmetric carbon. The enantiomers of cyclic ketones have also been separated as diastereomeric oximes by Pappo [114] in this reaction the racemic ketone was treated with R-2-amino-oxy-4-methylvaleric acid (48) in methanol/pyridine (10 1) at room temperature for 18 h. The diastereomers were separated on silica... 

Chiral oxazaborolidine catalysts were applied in various enantioselective transformations including reduction of highly functionalized ketones/ oximes or imines/ Diels-Alder reactions/ cycloadditions/ Michael additions, and other reactions. These catalysts are surprisingly small molecules compared to the practically efficient chiral phosphoric acids, cinchona alkaloids, or (thio)ureas hence, their effectiveness in asymmetric catalysis demonstrates that huge substituents or extensive hydrogen bond networks are not absolutely essential for successful as5unmetric organocatalysis. 

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