Tadao Harada

Recent developments in asymmetric reduction of ketones with biocatalysts

Herein we review recent advances in the asymmetric reduction of ketones by biocatalysts. Included are discussions on recent developments in methodologies to control enantioselectivities of catalytic reactions, and examples of practical applications that reduce various types of ketones are also shown.

Reactions of supercritical alcohols with unsaturated hydrocarbons

Abstract The reactions of some supercritical alcohols were investigated using 1,1-diphenylethylene, styrene, allylbenzene, and diphenylacetylene as the reaction partners. 1,1-Diphenylethylene in supercritical methanol was hydroxymethylated to afford 3,3-diphenyl-1-propanol as the major product. The alkenes containing a single and no conjugate phenyl group were also hydroxymethylated in supercritical methanol, but the reaction rates were significantly reduced when compared with that for 1,1-diphenylethylene. Styrene was converted to the hydroxyalkylated products in supercritical ethanol and 2-propanol as well as in supercritical methanol. The rates of the hydroxyalkylation of styrene were strongly dependent on the structures of the supercritical alcohols; the order of reactivity was 2-propanol>ethanol>methanol. The relation between the structures of the alcohols and the rates of hydroxyalkylation suggests that the reaction begins with an attack on the electrophile ( + CR 2 OH or δ+ CR 2 OH) by the pi electrons of the styrene double bond. All the examined alkenes afforded their hydrogenated derivatives other than the hydroxyalkylated ones. In addition, supercritical alcohols acted as hydroxyalkylating or hydrogenating reagents for the triple bond in the reaction with diphenylacetylene.

Enantio-differentiating hydrogenation of prochiral ketones over modified nickel

Abstract This article reviews the enantio-differentiating hydrogenation of prochiral ketones over a asymmetrically modified catalyst, focusing on the hydrogenation of simple prochiral alkanones. The parameters affecting catalytic activity and enantiodifferentiating ability are considerable in number, and each parameter should be optimized in order to attain a highperformance enantio-differentiating catalyst. Optimization of the parameters and the mode of enantio-differentiation are discussed and compared with the enantio-differentiating hydrogenation of β-ketoesters.

Progress of enantio-differentiating hydrogenation of prochiral ketones over asymmetrically modified nickel catalysts and a newly proposed enantio-differentiation model

This article reviews the enantio-differentiating hydrogenation of various prochiral ketones over asymmetrically modified Ni catalysts. Development from the discovery to the state of the art of the modified Ni catalyst is surveyed. Understanding and interpretation of this catalyst is discussed and new enantio-differentiation models are proposed.

Control on enantioselectivity with pressure for lipase-catalyzed esterification in supercritical carbon dioxide

Abstract The enantioselectivity of lipase-catalyzed esterification of 1-( p -chlorophenyl)-2,2,2-trifluoroethanol in supercritical carbon dioxide changed continuously from E =10 to 50 by decreasing the pressure at 55°C. The effect of the solvent on enantioselectivity was examined without changing the kind of solvent.

Organic synthesis using enzymes in supercritical carbon dioxide

Enzymes have been used in supercritical carbon dioxide (scCO2) rather than in the conventional media to make enzyme reactions greener. This review introduces some enzymatic asymmetric synthesis in scCO2 such as esterification by a lipase and reduction by an alcohol dehydrogenase. A carboxylation by a decarboxylase is also described.

Asymmetric synthesis of (R)-2-chloro-1-(m-chlorophenyl)ethanol using acetone powder of Geotrichum candidum

The asymmetric synthesis of (R)-2-chloro-1-(m-chlorophenyl)ethanol, a precursor for a key intermediate of an important class of drugs, was achieved by reduction of the corresponding ketone using an acetone powder of Geotrichum candidum with 98% ee and 94% yield based on the starting amount of ketone.

Asymmetric reduction of simple aliphatic ketones with dried cells of Geotrichum candidum

Simple aliphatic ketones such as 2-pentanone, 2-butanone, 3-hexanone, etc., were reduced with high yield and excellent enantioselectivity to the corresponding (S)-alcohols using dried cells of Geotrichum candidum.

Mode of enantioface-differentiation in the hydrogenation of 2-alkanone over an asymmetrically modified nickel catalyst

Abstract The enantioface-differentiating hydrogenation of 2-alkanone over tartaric acid-NaBr-modified Raney nickel (TA-NaBr-MRNi) gave an excellent optical yield when an appreciable amount of pivalic acid coexisted with the substrate. The function of tartaric acid and pivalic acid in the reaction process is as follows. (1) Tartrate adsorbed on the catalyst makes an associative complex with pivalic acid and 2-alkalone through hydrogen bonding by sharing its two hydroxyl groups with the CO group of pivalic acid and that of the 2-alkanone. (2) The repulsion between the alkyl group of pivalic acid and that of 2-alkanone in the associative complex fixes the adsorption mode of 2-alkanone on the catalyst in such a way that one enantioface of the substrate faces the nickel surface. The experimental results, which included stereochemistry and optical yield of the reaction, were in good agreement with the prediction from the proposed reaction model.

Application of an in situ modification of nickel catalysts to the enantio-differentiating hydrogenation of methyl acetoacetate

Abstract In situ modification (( R , R )-tartaric acid and NaBr were directly added to the reaction media) of fine Ni powder (FNiP) and reduced Ni catalysts was applied to the enantio-differentiating hydrogenation of methyl acetoacetate (MAA). The high optical yield of 89% was attained by the reduced Ni catalyst. This is the highest value reported so far for the hydrogenation of methyl acetoacetate using the in situ modification. The addition of a small amount of NaBr to the reaction media increased both the optical yield and hydrogenation rate, while the hydrogenation rate decreased with the addition of NaBr to the modification solution for the conventional modification method. NaBr added to the reaction media for the in situ modification would have both of the following roles: (i) Na + increased the optical yield and the hydrogenation rate; and (ii) Br − increased the optical yield and decreased the hydrogenation rate.