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ABSTRACT: A series of 3-oxoglutaric acid derivatives have been hydrogenated in different solvents in the presence of [RuCl(benzene)(S)-SunPhos]Cl (SunPhos=(2,2,2',2'-tetramethyl-[4,4'-bibenzo[d][1,3]dioxole]-5,5'-diyl)bis(diphenylphosphine)). Unlike simple β-keto acid derivatives, these advanced analogues can be readily hydrogenated in uncommon solvents such as THF, CH(2) Cl(2) , acetone, and dioxane with high enantioselectivities. Two possible catalytic cycles have been proposed to explain the different reactivities of these 1,3,5-tricarbonyl substrates in the tested solvents. The C-2 and C-4 substituents had notable but irregular influence on the reactivity and enantioselectivity of the reactions. More pronounced solvent effects were observed: the ee values increased from around 20 % in EtOH or THF to 90 % in acetone. Inversion of the product configuration was observed when the solvent was changed from EtOH to THF or acetone, and a mixed solvent system can lead to better enantioselectivity than a single solvent.
Chemistry 10/2012; · 5.93 Impact Factor
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ABSTRACT: Highly effective asymmetric hydrogenation of β-ketophosphonates in the presence of Ru-(S)-SunPhos as catalyst was realized; good to excellent enantioselectivities (up to 99.9% ee) and excellent diastereoselectivities (96:4) were obtained.
The Journal of Organic Chemistry 09/2012; 77(19):8401-9. · 4.45 Impact Factor
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ABSTRACT: By modulating the chelating priorities of the different directing groups in 3,5-diketo amides with the assistance from coordinating solvent, highly chemo- and enantioselective hydrogenation of the C3-carbonyls was achieved in the presence of [RuCl(benzene)(S)-SunPhos]Cl in THF.
Chemical Communications 07/2012; 48(71):8976-8. · 6.17 Impact Factor
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ABSTRACT: Finely-tuned ruthenium-catalyzed highly chemoselective and enantioselective hydrogenation of γ-halo-γ,δ-unsaturated-β-keto esters at the carbonyl group was achieved under neutral reaction conditions (ee up to 97%). Both olefin and alkenyl halogen moieties, which are labile under hydrogenation conditions, remained untouched during the reaction.
Chemical Communications 04/2012; 48(43):5352-4. · 6.17 Impact Factor
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ABSTRACT: A series of acid-labile, optically pure ε-substituted δ-ketal-β-hydroxy esters were obtained by a Ru-SunPhos catalyzed asymmetric hydrogenation of the corresponding ε-substituted δ-ketal-β-keto esters. CaCO(3) played a dual role in the hydrogenation reaction--removing the acid generated during the formation of the catalyst and maintaining the activity of the catalyst.
Chemical Communications 03/2012; 48(35):4247-9. · 6.17 Impact Factor
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ABSTRACT: Chemoselective reduction of the b-carbonyls in b, d-diketo acid derivatives was achieved through RuCl2 (PPh3)3 catalyzed homo-geneous hydrogenation. Tetrahydrofuran (THF) played a key role in the chemoselectivity control. This atom-economical protocol provided b-hydroxy-d-keto esters and amides as useful intermediates in good to excellent yields. The reduction of ketones to alcohols is a very fundamental organic transformation, 1 which has been routinely accomplished by various alumino-or borohydrides. 2 However, large-scale use of these stoichiometric reagents often suffers from safety concerns, high cost and tedious work-up. Besides, common reductants like NaBH 4 and LiAlH4 show hardly any chemoselectivity for poly-carbonyl substrates, 3 especially when the carbonyls are in similar steric and electronic environment. 4 For example, the selective reduction of the b, d-diketo acid derivatives at the desired position is important but difficult to control. As illustrated in Scheme 1, metal hydrides and their modifiers tend to reduce both b-and d-carbonyls and semi-reduction products can rarely be attained except for a few sterically hindered substrates. 5 Even many ketoreductases were unable to give an ideal chemoselectivity. 6 Several recently-developed biocatalysts reduced the d-carbonyls with spectacular chemo-and enantioselectivity, 6c,7 although few of them can reduce b-carbonyls equally well. 6c Moreover, the high costs and narrow substrate scope limited their applications. Until now, no practical reduction methods with good b-selectivity have been reported. Homogeneous hydrogenation has been increasingly employed in the reduction of unsaturated functionalities due to its unique merits. 8 Earlier attempts on the b-selective hydrogenation of b, d-diketo esters failed because the initial hydrogenation products easily underwent further hydrogenation in alcohols. 9 In 1999, Carpentier et al. 9a implemented a b-selective hydrogenation of methyl 3,5-dioxohexanoate with a Ru-BINAP system under the specified conditions (20 to 50 uC, 100 atm of H 2 , CH 2 Cl 2). However, the reactions must be carefully monitored by GLC during the course to avoid over hydrogenation. In our earlier studies on the asymmetric hydrogenation of 3-oxoglutaric acid derivatives, 10 we discovered that a coordinative solvent like THF helped to modulate the coordination ability of carbonyls in b-keto esters and b-keto amides. The latter were hydrogenated much more quickly than the former. Based on these conclusions, we tried the hydrogenation of various b, d-diketo acid derivatives in THF, which was an ineffective solvent for the catalytic hydrogenation of many functionalized ketones. 11 To our pleasure, good to excellent yields were obtained with RuCl 2 (PPh 3) 3 as the catalyst under moderate H 2 pressure (20 bar). Simple optimization of the reaction conditions with 1b and 1m was performed. It took 30 h for 90% conversion of 1m at 50 uC under 5 bar of H 2 with S/C = 100. At 90 uC, the reaction became complex for esters but was still good for amides. Thus we performed hydrogenation reactions at 70 uC and at 20 bar of H 2 . Under such relatively mild conditions, all the tested substrates converted to the desired products in 8 to 15 h. A prolonged reaction time (especially for the amides) after full conversion (8 h for most amides) lead to no over reduction. The resistance to further hydrogenation of the b-hydroxy amides was illustrated by the fact that 2m remained untouched when subjected to harsher conditions (1% mmol of catalyst, 20 bar of H 2 , 95 uC, 8 h). Therefore, cautious monitoring of the hydrogenation process is unnecessary. As listed in Table 1, the esters 1a–e gave the desired products in good yields. The (hetero)aryl substituted esters (entries 3–5, Table 1) gave somewhat higher yields than the alkyl substituted esters (entries 1–2, Table 1), as the latter was partially converted to some
RSC Advances. 02/2012;
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ABSTRACT: Chemoselective reduction of the b-carbonyls in b, d-diketo acid derivatives was achieved through RuCl 2 (PPh 3) 3 catalyzed homo-geneous hydrogenation. Tetrahydrofuran (THF) played a key role in the chemoselectivity control. This atom-economical protocol provided b-hydroxy-d-keto esters and amides as useful intermediates in good to excellent yields.
RSC Advances. 02/2012; 2:3214-3216.
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ABSTRACT: Various substituted aryl-pyridyl ketones were hydrogenated in the presence of Ru-XylSunPhos-Daipen bifunctional catalytic system with enantiomeric excesses up to 99.5%. Upon introduction of a readily removable ortho-bromo atom to the phenyl ring, enantiomerically enriched 4-chlorophenylpyridylmethanol was obtained by hydrogenation method with 97.3% ee, which provided an important chiral intermediate for some histamine H(1) antagonists.
The Journal of Organic Chemistry 11/2011; 77(1):612-6. · 4.45 Impact Factor
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ABSTRACT: A series of enantiomerically pure γ-heteroatom substituted β-hydroxy esters were synthesized with high enantioselectivities (up to 99.1% ee) by hydrogenation of γ-heteroatom substituted β-keto esters in the presence of Ru-(S)-SunPhos catalyst. These asymmetric hydrogenations provide key building blocks for a variety of naturally occurring and biologically active compounds.
The Journal of Organic Chemistry 11/2011; 76(22):9444-51. · 4.45 Impact Factor
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ABSTRACT: Upon comparison of hydrogenation rates of various β-ketocarboxylic acid derivatives, β-ketoamides were found to be hydrogenated slightly faster than β-ketoesters in EtOH in the presence of [RuCl(benzene)(S)-SunPhos]Cl at 70 °C with 20 bar of hydrogen. In THF these differences were so sharpened that β-ketoamides were hydrogenated even faster than in EtOH while the esters were extremely slow. Based on these findings, a series of 3-oxoglutaric acid derived with ester and amide moieties on the two ends were hydrogenated to 3-hydroxyl products with high enantioselectivities.
Organic Letters 08/2011; 13(15):3876-9. · 5.86 Impact Factor
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ABSTRACT: Highly effective asymmetric hydrogenation of protected ethyl 1-(2-aminoaceto)cyclopropane carboxylates in the presence of [RuCl(benzene)(S)-SunPhos]Cl was realized, and high enantioselectivities (up to 98.7% ee) were obtained. This asymmetric hydrogenation provides a key intermediate for the enantioselective synthesis of (S)-7-amino-5-azaspiro[2.4]heptane moiety of quinolone antibacterial agents.
The Journal of Organic Chemistry 03/2011; 76(8):2807-13. · 4.45 Impact Factor
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ABSTRACT: In this study, a new bacterial strain MEL09, which produces acetoin at high concentrations, was isolated from solid cultures of traditional Chinese vinegar. Based on physiological and biochemical characteristics as well as the 16S rDNA gene sequence, strain MEL09 was identified as Bacillus licheniformis. To improve acetoin production by B. licheniformis MEL09, medium composition and culture conditions were optimized by varying one factor at a time and using orthogonal array tests. Under these optimized conditions, the maximum acetoin concentration achieved was 41.26 g l−1, with 41.26% glucose conversion efficiency (84.39% of theoretical glucose conversion efficiency). This increase is 84.86% over the initial condition and is, to our knowledge, the highest acetoin level ever reported using fermentation methods.
Process Biochemistry.
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RSC Advances. 2(8):3214-3216.
