Asymmetric reduction of a-keto esters

Asymmetric reduction of a-keto esters The chromium-complexed a-keto ester 1 is reduced to the carbinol by sodium borohydride with surprisingly high... 

The reagent is also useful for asymmetric reduction of a-keto esters, particularly a-keto /-butyl esters. Thus /-butyl pyruvate is reduced to (S)-/-butyl lactate in 100% ee.1... 

Asymmetric reduction of a-keto esters. / lkyl pyruvates are rapidly reduced by this borane to alkyl (S)-lactates (equation I). The jxtent of asymmetric induction depends to some extent on the temperature and the size if the ester group. Quantitative optical... 

Asymmetric reduction of a-keto esters, typically pyruvates and phenylglyoxylates, is effected by chiral rhodium complex-catalyzed hydrosilylation . Optical yields of lactates are higher than those obtained for simple prochiral ketones. The ester group as well as the hydrosilane used effects the extent of asymmetric induction. A high optical yield is attained for M-propyl pyruvate using a-naphthylphenylsilane (85.4% e.e.p ... 

II. Asymmetric Reduction of a-Keto Esters and a-Keto Acids. . 151... 

Fig. 3. Examples of asymmetric reduction of a-keto esters (Prelog et al., 1954).

Fukuzumi S, Kondo Y, Tanaka T (1983c) Evidence for a single electron transfer activation in the hydride transfer from an NADH model compound to tetracyanoethylene. Chem Lett 751-754 Fushimi M, Baba N, Oda J, Inouye Y (1980) Asymmetric reduction of a-keto-esters and trifluoroacetophenone with N-anionized Hantzsch ester. Bull Inst Chem Res Kyoto Univ 58 357-365 Gase RA, Boxhoorn G, Pandit UK (1976) Metal-complex mediated catalysis of reduction of 2-benzoylpyridine by an NADH-model. 

The asymmetric reduction of a-keto-esters has been achieved via catalytic hydro-silylation followed by hydrolysis (Scheme 20). The rhodium catalysts used in these... 

Pennachio, A., Giordano, A., Rossi, M., and Raia, C.A. (2011) Asymmetric reduction of a-keto esters with Thermus thermophilus NADH-dependent carbonyl reductase using glucose dehydrogenase and alcohol dehydrogenase for cofactor regeneration. Eur. J. Org. Chem., 2011 (23), 4361-4366. 

Yamada, H., Shimizu, S., Kataoka, M., Sakai, H., and Miyoshi, T. 1990. A novel NADPH-dependent aldehyde reductase, catalyzing asymmetric reduction of (1-keto esters, from Sporobolomyces salmonicolor. Purification and characterization. FEMS Microbiol. Lett., 70, 45 18. 

Asymmetric reactions of a-keto esters of (-)-l.2 Reduction of the a-keto ester (2) of (- )-8-phenylmenthol (1) with potassium triisopropoxyborohydride proceeds in 90% de to give the lactate ester (R)-3 with chirality opposite to that obtained by reaction of... 

Baker s yeast offers the synthetic chemist an enzymatic method for the asymmetric reduction of p-keto esters, a-hydroxyaldehydes and ketones, and p-diketones. Reviews (a) Rene Csuk, R. Glaenzer, B. 1. Chem. Rev. 1991, 91, 49-97. (b) Servi, S. Synthesis, 1990, 1-25. 

A considerable amount of work has been carried out on the animation with azodicarboxylic esters of p-hydroxy esters, a class of compounds where both enantiomers are readily available by asymmetric reduction of 3-keto esters. Yields are in the range of 50-70% for lithium115,415-417 (Eq. 115),417 magnesium,416 zinc,416,418-424 and titanium enolates,416 but diastereoselectivities are highest with zinc enolates (Eq. 116)416 Attack from the less hindered side of zinc enolate 57 accounts for the observed anti selectivity. Similar results are obtained with the other enantiomer 416 The lithium enolate of the rigidized derivative of ester 56 gives higher yields with a somewhat reduced anti selectivity (Eq. 117). 416... 

The asymmetric reduction of various keto-esters has been reported. The hydrogenation of a-keto-esters to chiral lactates is catalysed by rhodium(l) complexes of the ligand (2) [equation (3)] the lactates are obtained quantitatively with optical yields of up to 76%. 

Hydroxy-esters. - Once again, most contributions to this area involve the synthesis of chiral hydroxy-esters. Almost complete enantioselectivity is achieved in the reduction of a-keto-esters to a-hydroxy-esters using Alpine-Borane (B-(3-pinanyl)-9-BBN) derived from either (+)- or (-)-a-pinene when the reactions are carried out at relatively high concentrations (>2M). Many other types of prochiral ketones are also reduced with excellent asymmetric inductions although 3-keto-esters may not be particularly suitable substrates as ethyl acetoacetate is reduced to ethyl 3-hydroxybutanoate with an enantiomeric excess of only... 

Ogura K, Fujita M, lida H (1980) A two-phase reaction catalyzed by a protein. Asymmetric oxidation of formaldehyde dithioacetals with aqueous sodium metaperiodate. Tetrahedron Lett 21 2233-2236 Ohnishi Y, Kagami M, Ohno A (1975a) Reduction by a model of NAD(P)H. Effect of metal ion and stereochemistry on the reduction of a-keto esters by 1,4-dihydronicotinamide derivatives. J Am Chem Soc 97 4766-4768... 

However, unlike Eapine-Borane and Alpine-Borane Prapine-Borane fails to provide improved asymmetric induction in the reduction of a-keto esters (Table 26.19) [1]. 

The intermolecular asymmetric reduction of various keto esters with (-)-DIP-Cl has also been investigated. Interestingly, the opposite stereochemistry is observed for the products from the reduction of aromatic and aliphatic a-keto esters (Scheme 23.55). Due to facile enolization, reductions of P-keto esters are unsuccessful. 

B. Asymmetric Reduction of p-Keto Esters and a p-Keto Sulfide... 

A. Chemical Methods 1. Asymmetrical Reduction of p-Keto Esters... 

Further examples, albeit with somewhat lower e.e. values, have been reported [237,240-245]. The course of the reduction of a-keto esters 199 (Fig. 51) can be altered and controlled by using organic solvents instead of water. In addition, it has been found that a-hydroxy esters 200 produced by the yeast reduction are decomposed enzymically in water, and this asymmetrical decomposition does not take place during the reduction in an organic solvent such as benzene [246-248]. 

The Ni/tartaric acid/NaBr catalyst system has been extensively studied. A variety of ketone substrates have been reduced with Ni/tartaric acid/NaBr catalysts with variable enantioselectivities, but the highest (>85% ee) are obtained for the reductions of P-keto esters and P-diketones (Schemes 12.60 and 12.61).5 Asymmetric reduction of diketones results in the formation of mesa and chiral diols. The highest meso chiral diol ratio of 2 98 and enantioselectivities of 98% ee are obtained with modified Raney nickel catalysts treated by sonication.5... 

Asymmetric oxidoreductions performed in isopropyl ether allow syntheses of optically active alcohols with ee >95% on a 1-10 mmol scale. Nakamura et al. investigated the effect of organic solvents on the reduction of ot-keto esters mediated by bakers yeast [140]. The reduction of ethyl 2-oxoheptanoate was tested in various solvents. Best results were achieved with benzene so further experiments were performed with benzene. Conversion only takes place in the presence of small amounts of water. The reduction of six ot-keto esters was examined regarding the stereoselectivity of the corresponding ot-hydroxy esters. The reactions were performed in aqueous systems as well as in benzene. In aqueous systems, the formed hydroxy esters show (S)-stereoselectivity while the stereochemistry of the reaction shifts markedly towards the production of (/ )-ot-hydroxy esters in benzene. 

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