- Amino alcohol effects on the ruthenium(II)-catalysed asymmetric transfer hydrogenation of ketones in propan-2-ol
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A ruthenium(II) complex generated in situ from [{RuCl2(η6-C6Me6)}2], (1S,2S)-2-methylamino-1,2-diphenylethanol and KOH serves as an efficient catalyst for asymmetric transfer hydrogenation of acetophe
- Takehara, Jun,Hashiguchi, Shohei,Fujii, Akio,Inoue, Shin-Ichi,Ikariya, Takao,Noyori, Ryoji
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- Asymmetric reduction of ketones by the acetone powder of Geotrichum candidum
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Reduction of ketones with a reductant, 2-alkanol, by the acetone powder of Geotrichum candidum affords the corresponding (S)-alcohols of excellent ee in high yield.
- Nakamura, Kaoru,Kitano, Kazutada,Matsuda, Tomoko,Ohno, Atsuyoshi
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- Pushing the limits: Cyclodextrin-based intensification of bioreductions
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The asymmetric reduction of ketones is a frequently used synthesis route towards chiral alcohols. Amongst available chemo- and biocatalysts the latter stand out in terms of product enantiopurity. Their application is, however, restricted by low reaction output, often rooted in limited enzyme stability under operational conditions. Here, addition of 2-hydroxypropyl-β-cyclodextrin to bioreductions of o-chloroacetophenone enabled product concentrations of up to 29 % w/v at full conversion and 99.97 % e.e. The catalyst was an E. coli strain co-expressing NADH-dependent Candida tenuis xylose reductase and a yeast formate dehydrogenase for coenzyme recycling. Analysis of the lyophilized biocatalyst showed that E. coli cells were leaky with catalytic activity found as free-floating enzymes and associated with the biomass. The biocatalyst was stabilized and activated in the reaction mixture by 2-hydroxypropyl-β-cyclodextrin. Substitution of the wild-type xylose reductase by a D51A mutant further improved bioreductions. In previous optimization strategies, hexane was added as second phase to protect the labile catalyst from adverse effects of hydrophobic substrate and product. The addition of 2-hydroxypropyl-β-cyclodextrin (11 % w/v) instead of hexane (20 % v/v) increased the yield on biocatalyst 6.3-fold. A literature survey suggests that bioreduction enhancement by addition of cyclodextrins is not restricted to specific enzyme classes, catalyst forms or substrates.
- Rapp, Christian,Nidetzky, Bernd,Kratzer, Regina
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- B-Chlorodiiso-2-ethylapopinocampheylborane: An extremely efficient chiral reducing agent for the reduction of prochiral ketones of intermediate steric requirements
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B-Chlorodiiso-2-ethylapopinocampheylborane, Eap2BCl, prepared from 2-ethylapopinene and chloroborane-methyl sulfide reduces prochiral ketones of intermediate steric requirements to the product alcohols in very high ee.
- Brown,Veeraraghavan Ramachandran,Teodorovic,Swaminathan
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- Chiral Ru complex immobilized on mesoporous materials by ionic liquids as heterogeneous catalysts for hydrogenation of aromatic ketones
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Four kinds of mesoporous material-supported ionic liquid phase catalysts containing chiral Ru complex were synthesized using mesoporous MCM-41, MCM-48, SBA-15 and amorphous SiO2, respectively. The results of N2 sorption and XRD indicated the successful immobilization of chiral Ru complex inside the channels of the mesoporous materials. These immobilized catalysts were evaluated in the asymmetric hydrogenation of aromatic ketones and the reaction conditions were optimized. Comparable catalytic activities and enantioselectivities to those of nonimmobilized counterpart were obtained. Moreover, all the four catalysts were stable and could be easily recovered for reuse for at least four times without obvious decrease in conversions and ee values. Especially, the SiO2-based catalyst still preserved high activity and enantioselectivity in the fifth run. The comparison experiments indicated that the two kinds of ionic liquids in the heterogeneous catalyst were beneficial to the enhancement of the stability of active species.
- Lou, Lan-Lan,Dong, Yanling,Yu, Kai,Jiang, Shu,Song, Yang,Cao, Song,Liu, Shuangxi
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- Asymmetric reduction of ketones with a germinated plant
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A germinated radish sprout was used as a novel type of biocatalyst for the asymmetric reduction of ketones. The reactions proceeded with high enantioselectivities (>99% ee). The biocatalyst is easily obtainable from commercially available vegetable seeds and is very easy to use.
- Matsuo, Kiyoko,Kawabe, Sei-ichiro,Tokuda, Yosuke,Eguchi, Takashi,Yamanaka, Rio,Nakamura, Kaoru
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- Stereoselective Reduction of Prochiral Ketones, Using Aluminum Hydride Reagents Prepared from LiAlH4 and Chiral Diethanolamines
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The asymmetric reduction of prochiral ketones to chiral secondary alcohols by LiAlH4, modified with optically active diethanolamines, was studied.Asymmetric inductions of up to 94percent were obtained with these reagents.The stereoselectivity of the reaction was found to depend both upon the temperature at which the reduction was performed and upon the conditions under which the chiral aluminum hydride reagent had been prepared.By changing the substituents at the carbon atom α to nitrogen in the chiral auxiliary, either the (R)- and (S)-enantiomer of the secondary alcohol could be obtained in excess.
- Vries, Erik F.J. de,Brussee, Johannes,Kruse, Chris G.,Gen, Arne van der
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- Synthesis of a fluorous ligand and its application for asymmetric addition of dimethylzinc to aldehydes
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A new fluorous ligand was synthesized from the acetonide of dimethyl tartarate, which showed excellent asymmetric induction on the addition of dimethylzinc to aldehydes. This ligand will be useful for synthesis of bioactive compounds with a methyl carbinol moiety. It could be recycled without using a fluorous solvent or a fluorous column.
- Sokeirik, Yasser S.,Mori, Hiroyuki,Omote, Masaaki,Sato, Kazuyuki,Tarai, Atsushi,Kumadaki, Itsumaro,Ando, Akira
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- Enantioselective transfer hydrogenation of ketones with planar chiral?ruthenocene-based phosphinooxazoline ligands
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1,2-Disubstituted planar chiral ruthenocene-based phosphinooxazoline ligands (Rc-PHOX, 3 and 4) were synthesized easily and applied in the transfer hydrogenation of ketones to chiral alcohols using 2-propanol as a source of hydrogen with excellent enantio
- Liu, Delong,Xie, Fang,Zhao, Xiaohu,Zhang, Wanbin
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- Asymmetric transfer hydrogenation of aromatic ketones catalyzed by SBA-15 supported Ir(I) complex under mild conditions
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A heterogeneous catalyst of Ir(I)-9-amino epi-cinchonine complex immobilized on the surface of mesoporous SBA-15 was firstly synthesized and used in the asymmetric transfer hydrogenation of aromatic ketones. Enhanced enantioselectivity compared with homog
- Shen, Yanbin,Chen, Qiu,Lou, Lan-Lan,Yu, Kai,Ding, Fei,Liu, Shuangxi
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- Oxidative kinetic resolution of secondary alcohols with salen-Mn(III)/NBS/NaClO system
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The oxidative kinetic resolution of racemic secondary alcohols was efficiently catalyzed by a chiral Mn(III)-salen complex using sodium hypochlorite (NaClO) as an oxidant in the presence of 8 mol% N-bromosuccinimide (NBS) in a dichloromethylene-water mixture solvent at room temperature. Excellent ee's (up to 99 %) of chiral secondary alcohols were achieved in most cases.
- Zhang, Yuecheng,Gao, Baosheng,Zhou, Qiao,Zhao, Jiquan
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- Enhancing cofactor regeneration of cyanobacteria for the light-powered synthesis of chiral alcohols
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Cyanobacteria Synechocystis sp. PCC 6803 was exploited as green cell factory for light-powered asymmetric synthesis of aromatic chiral alcohols. The effect of temperature, light, substrate and cell concentration on substrate conversions were investigated. Under the optimal condition, a series of chiral alcohols were synthesized with conversions up to 95% and enantiomer excess (ee) > 99%. We found that the addition of Na2S2O3 and Angeli's Salt increased the NADPH content by 20% and 25%, respectively. As a result, the time to reach 95% substrate conversion was shortened by 12 h, which demonstrated that the NADPH regeneration and hence the reaction rates can be regulated in cyanobacteria. This blue-green algae based biocatalysis showed its potential for chiral compounds production in future.
- Fan, Jianhua,Zhang, Yinghui,Wu, Ping,Zhang, Xiaoyan,Bai, Yunpeng
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- Cinchona-Alkaloid-Derived NNP Ligand for Iridium-Catalyzed Asymmetric Hydrogenation of Ketones
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Most ligands applied for asymmetric hydrogenation are synthesized via multistep reactions with expensive chemical reagents. Herein, a series of novel and easily accessed cinchona-alkaloid-based NNP ligands have been developed in two steps. By combining [Ir(COD)Cl]2, 39 ketones including aromatic, heteroaryl, and alkyl ketones have been hydrogenated, all affording valuable chiral alcohols with 96.0-99.9% ee. A plausible reaction mechanism was discussed by NMR, HRMS, and DFT, and an activating model involving trihydride was verified.
- Zhang, Lin,Zhang, Ling,Chen, Qian,Li, Linlin,Jiang, Jian,Sun, Hao,Zhao, Chong,Yang, Yuanyong,Li, Chun
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supporting information
p. 415 - 419
(2022/01/12)
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- Highly Active Cooperative Lewis Acid—Ammonium Salt Catalyst for the Enantioselective Hydroboration of Ketones
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Enantiopure secondary alcohols are fundamental high-value synthetic building blocks. One of the most attractive ways to get access to this compound class is the catalytic hydroboration. We describe a new concept for this reaction type that allowed for exceptional catalytic turnover numbers (up to 15 400), which were increased by around 1.5–3 orders of magnitude compared to the most active catalysts previously reported. In our concept an aprotic ammonium halide moiety cooperates with an oxophilic Lewis acid within the same catalyst molecule. Control experiments reveal that both catalytic centers are essential for the observed activity. Kinetic, spectroscopic and computational studies show that the hydride transfer is rate limiting and proceeds via a concerted mechanism, in which hydride at Boron is continuously displaced by iodide, reminiscent to an SN2 reaction. The catalyst, which is accessible in high yields in few steps, was found to be stable during catalysis, readily recyclable and could be reused 10 times still efficiently working.
- Titze, Marvin,Heitk?mper, Juliane,Junge, Thorsten,K?stner, Johannes,Peters, René
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supporting information
p. 5544 - 5553
(2021/02/05)
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- Single-Point Mutant Inverts the Stereoselectivity of a Carbonyl Reductase toward β-Ketoesters with Enhanced Activity
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Enzyme stereoselectivity control is still a major challenge. To gain insight into the molecular basis of enzyme stereo-recognition and expand the source of antiPrelog carbonyl reductase toward β-ketoesters, rational enzyme design aiming at stereoselectivity inversion was performed. The designed variant Q139G switched the enzyme stereoselectivity toward β-ketoesters from Prelog to antiPrelog, providing corresponding alcohols in high enantiomeric purity (89.1–99.1 % ee). More importantly, the well-known trade-off between stereoselectivity and activity was not found. Q139G exhibited higher catalytic activity than the wildtype enzyme, the enhancement of the catalytic efficiency (kcat/Km) varied from 1.1- to 27.1-fold. Interestingly, the mutant Q139G did not lead to reversed stereoselectivity toward aromatic ketones. Analysis of enzyme–substrate complexes showed that the structural flexibility of β-ketoesters and a newly formed cave together facilitated the formation of the antiPrelog-preferred conformation. In contrast, the relatively large and rigid structure of the aromatic ketones prevents them from forming the antiPrelog-preferred conformation.
- Li, Aipeng,Wang, Ting,Tian, Qing,Yang, Xiaohong,Yin, Dongming,Qin, Yong,Zhang, Lianbing
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p. 6283 - 6294
(2021/03/16)
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- Ruthenium-catalyzed hydrogenation of aromatic ketones using chiral diamine and monodentate achiral phosphine ligands
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The Ru-catalyzed asymmetric hydrogenation of ketones with chiral diamine and monodentate achiral phosphine has been developed. A wide range of ketones were hydrogenated to afford the corresponding chiral secondary alcohols in good to excellent enantioselectivities (up to 98.1% ee). In addition, an appropriate mechanism for the asymmetric hydrogenation was proposed and verified by NMR spectroscopy.
- Wang, Mengna,Zhang, Ling,Sun, Hao,Chen, Qian,Jiang, Jian,Li, Linlin,Zhang, Lin,Li, Li,Li, Chun
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- Biocatalytic preparation of a key intermediate of antifungal drugs using an alcohol dehydrogenase with high organic tolerance
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In this study, an alcohol dehydrogenase derived from Lactobacillus kefir (LkADH) was engineered and a simple and practical bioreduction system was developed for the preparation of (R)-2-chloro-1-(2, 4-dichlorophenyl) ethanol ((R)-CDPO), a key intermediate for the synthesis of antifungal drugs. Through active pocket iterative saturation mutagenesis, mutant LkADH-D18 (Y190C/V196L/M206H/D150H) was obtained with high stereoselectivity (99% ee, R vs 87% ee, S) and increased activity (0.44 μmol·min?1·mg?1). LkADH-D18 demonstrated NAD(P)H regeneration capability using a high concentration of isopropanol (IPA) as a co-substrate. Using 40% IPA (v/v), 400 mM of (R)-CDPO (90.1 g·L-1) was obtained via complete substrate conversion using 40 mg·mL?1 LkADH-D18 wet cells. The biocatalytic process catalyzed at constant pH with the cheap co-solvent IPA contributed to improved isolated yield of (R)-CDPO (97%), lower reaction cost, and simpler downstream purification, indicating the potential utility of LkADH-D18 in future industrial applications.
- Yan, Jinrong,Wang, Xiaojing,Li, Fangling,Yang, Lei,Shi, Guixiang,Sun, Weihang,Shao, Lei,Huang, Junhai,Wu, Kai
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supporting information
(2021/10/20)
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- Tridentate nitrogen phosphine ligand containing arylamine NH as well as preparation method and application thereof
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The invention discloses a tridentate nitrogen phosphine ligand containing arylamine NH as well as a preparation method and application thereof, and belongs to the technical field of organic synthesis. The tridentate nitrogen phosphine ligand disclosed by the invention is the first case of tridentate nitrogen phosphine ligand containing not only a quinoline amine structure but also chiral ferrocene at present, a noble metal complex of the type of ligand shows good selectivity and extremely high catalytic activity in an asymmetric hydrogenation reaction, meanwhile, a cheap metal complex of the ligand can also show good selectivity and catalytic activity in the asymmetric hydrogenation reaction, and is very easy to modify in the aspects of electronic effect and space structure, so that the ligand has huge potential application value. A catalyst formed by the ligand and a transition metal complex can be used for catalyzing various reactions, can be used for synthesizing various drugs, and has important industrial application value.
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Paragraph 0095-0102; 0105-0109
(2021/06/26)
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- RETRACTED ARTICLE: The Manganese(I)-Catalyzed Asymmetric Transfer Hydrogenation of Ketones: Disclosing the Macrocylic Privilege
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The bis(carbonyl) manganese(I) complex [Mn(CO)2(1)]Br (2) with a chiral (NH)2P2 macrocyclic ligand (1) catalyzes the asymmetric transfer hydrogenation of polar double bonds with 2-propanol as the hydrogen source. Ketones (43 substrates) are reduced to alcohols in high yields (up to >99 %) and with excellent enantioselectivities (90–99 % ee). A stereochemical model based on attractive CH–π interactions is proposed.
- Passera, Alessandro,Mezzetti, Antonio
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supporting information
p. 187 - 191
(2019/12/11)
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- Asymmetric Catalytic Meerwein-Ponndorf-Verley Reduction of Ketones with Aluminum(III)-VANOL Catalysts
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We report herein an efficient aluminum-catalyzed asymmetric MPV reduction of ketones with broad substrate scope and excellent yields and enantiomeric inductions. A variety of aromatic (both electron-poor and electron-rich) and aliphatic ketones were converted to chiral alcohols in good yields with high enantioselectivities (26 examples, 70-98percent yield and 82-99percent ee). This method operates under mild conditions (-10 °C) and low catalyst loading (1-5 mol percent). Furthermore, this process is catalyzed by the earth-abundant main-group element aluminum and employs 2-propanol as the hydride source.
- Guan, Yong,Mohammadlou, Aliakbar,Staples, Richard,Sullivan, Ryan P.,Wulff, William D.,Yin, Xiaopeng,Zheng, Li
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p. 7188 - 7194
(2020/07/21)
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- Porous Organic Frameworks Featured by Distinct Confining Fields for the Selective Hydrogenation of Biomass-Derived Ketones
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The asymmetric hydrogenation of biomass-derived molecules for the preparation of single enantiomer compounds is an effective method to reduce the rapid consumption of fossil resources. Porous organic frameworks (POFs) with pure organic surfaces may provide unusual confinement effects for organic substrates in chiral catalysis. Here, a series of POF catalysts are designed with chiral active centers decorated into sharply defined one-dimensional channels with diameters in the range of 1.2–2.9 nm. Due to the synergistic effect originating from the conjugated inner wall, the POF material (aperture size 2.4 nm) concentrates over 90% of aromatic species into the porous architecture, and its affinity is one or two orders of magnitude higher than those of classical porous solids. As determined by PBE+D3 calculation, the phenyl fragment reveals strong π–π interaction for steric hindrance around the metal active site to achieve stronger asymmetric induction. Therefore, this POF catalyst achieves high conversion (>99% yield) and enantioselectivity (>99% ee) for various substrates. The advantages of using the POF platform as a chiral catalyst can provide new perspectives on POF-based solid-state host–guest chemistry and asymmetric heterogeneous catalysis.
- Yang, Yajie,Deng, Dan,Zhang, Shenli,Meng, Qinghao,Li, Zhangnan,Wang, Zeyu,Sha, Haoyan,Faller, Roland,Bian, Zheng,Zou, Xiaoqin,Zhu, Guangshan,Yuan, Ye
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- An iron variant of the Noyori hydrogenation catalyst for the asymmetric transfer hydrogenation of ketones
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We report the design of a new iron catalyst for the asymmetric transfer hydrogenation of ketones. This type of iron catalyst combines the structural characteristics of the Noyori hydrogenation catalyst (an axially chiral 2,2′-bis(phosphino)-1,1′-binaphthyl fragment and the metal-ligand bifunctional motif) and an ene(amido) group that can activate the iron center. After activation by 8 equivalents of potassiumtert-butoxide, (SA,RP,SS)-7aand (SA,RP,SS)-7bare active but nonenantioselective catalysts for the transfer hydrogenation of acetophenone and α,β-unsaturated aldehydes at room temperature in isopropanol. A maximum turnover number of 14480 was observed for (SA,RP,SS)-7ain the reduction of acetophenone. The right combination of the stereochemistry of the axially chiral 2,2′-bis(phosphino)-1,1′-binaphthyl group and the carbon-centered chiral amine-imine moiety in (SA,RP,RR)-7b′afforded an enantioselective catalyst for the preparation of chiral alcohols with moderate to good yields and a broad functional group tolerance.
- Huo, Shangfei,Wang, Qingwei,Zuo, Weiwei
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supporting information
p. 7959 - 7967
(2020/06/26)
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- Enantioselective Hydroboration of Ketones Catalyzed by Rare-Earth Metal Complexes Containing Trost Ligands
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Four chiral dinuclear rare-earth metal complexes [REL1]2 (RE = Y(1), Eu(2), Nd(3), La (4)) stabilized by Trost proligand H3L1 (H3L1 = (S,S)-2,6-bis[2-(hydroxydiphenylmethyl)pyrrolidin-1-ylmethyl]-4-methylphenol) were first prepared, and all were characterized by X-ray diffraction. Complex 4 was employed as the catalyst for enantioselective hydroboration reaction of substituted ketones, and the corresponding secondary alcohols with excellent yields and high ee values were obtained using reductant HBpin. The same result was also achieved using the combination of lanthanium amides La[N(SiMe3)2]3 with Trost proligand H3L1 in a 1:1 molar ratio. The experimental findings and DFT calculation revealed the possible mechanism of the enantioselective hydroboration reaction and defined the origin of the enantioselectivity in the current system.
- Lu, Chengrong,Sun, Yuli,Xue, Mingqiang,Zhao, Bei
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p. 10504 - 10513
(2020/09/23)
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- Optimisation, scope and advantages of the synthesis of chiral phenylethanols using whole seeds of Bauhinia variegata L. (Fabaceae) as a new and stereoselective bio-reducer of carbonyl compounds
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With the aim of finding new methods for environmentally friendly synthesis of chiral phenylethanols, a screening was carried out to identify seeds that could be used as a biocatalyst capable of reducing stereoselectively prochiral ketones. As a result, seeds of Bauhinia variegata L. (Fabaceae) were identified as being an efficient and stereoselective biological reducer of acetophenone to produce (S)-1-phenylethanol (conversion of 98% and 99 e.e.%). Then, to optimise the reductive process, the effects of some variables such as temperature, load of substrate, pH, co-solvent, and reuse and storability of the seeds as a function of time were established. Utilising the optimal reaction conditions, nineteen substituted acetophenones were reduced to their corresponding chiral alcohols with a conversion ranging from 30% to 98% and enantiomeric excess of between 65% and >99%, and in addition, useful key intermediates were also obtained by the synthesis of drugs. The scope and advantages of this new biocatalytic synthetic method are also discussed.Research highlights A screening was carried out to identify seeds that could be used as a biocatalyst Seeds of Bauhinia variegata have been identified as an efficient biocatalyst to reduce carbonyl compounds. Acetophenone and substituted acetophenones were reduced with high stereoselectivity. Some key intermediates were synthetised using this methodology. Seeds can be stored for twenty-four months without loss of activity.
- Aimar, Mario L.,Bordón, Daniela L.,Cantero, Juan J.,Decarlini, María F.,Demmel, Gabriela I.,Rossi, Laura I.,Ruiz, Gustavo M.,Vázquez, Ana M.
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- Control of enantioselectivity in the enzymatic reduction of halogenated acetophenone analogs by substituent positions and sizes
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We utilized acetophenone reductase from Geotrichum candidum NBRC 4597 (GcAPRD), wild type and Trp288Ala mutant, to reduce halogenated acetophenone analogs to their corresponding (S)- and (R)-alcohols beneficial as pharmaceutical intermediates. Reduction by wild type resulted in excellent (S)-enantioselectivity for all of the substrates tested. Meanwhile, reduction by Trp288Ala resulted in high (R)-enantioselectivity for the reduction of 4′ substituted acetophenone and 2′-trifluoromethylacetophenone. In addition to that, we were able to control the enantioselectivity of Trp288Ala by the positions and sizes of the halogen substituents.
- Koesoema, Afifa Ayu,Standley, Daron M.,Ohshima, Shusuke,Tamura, Mayumi,Matsuda, Tomoko
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supporting information
(2020/03/23)
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- Fine-tuning of the substrate binding mode to enhance the catalytic efficiency of an: Ortho -haloacetophenone-specific carbonyl reductase
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Carbonyl reductase BaSDR1 has been identified as a potential ortho-haloacetophenone-specific biocatalyst for the synthesis of chiral 1-(2-halophenyl)ethanols due to its excellent stereoselectivity. However, the catalytic efficiency of BaSDR1 is far below the required level for practical applications. Thus, fine-tuning of the substrate binding mode, which aimed at maximum preservation of the positive factors for substrate specificity and stereoselectivity, was proposed as a tentative strategy for enhancing its catalytic efficiency. The designed mutants Q139S, D253Y and Q139S/D253Y showed significantly enhanced catalytic efficiency. Remarkably, the variants Q139S and Q139S/D253Y exhibited a more than 9-fold improvement in catalytic efficiency (kcat/Km) toward substrates 6a and 11a, respectively. More importantly, none of the variants caused activity-stereoselectivity trade-off and all variants exhibited excellent stereoselectivity (99% ee). Analysis of variant-substrate complexes showed that the mutations indeed enable the fine-tuning of the substrate binding mode. New strengthening factors for consolidating the productive conformation were introduced while the original positive factors were preserved. Furthermore, at a substrate concentration of 100 mM, recombinant E. coli whole cells expressing the BaSDR1 mutants were successfully applied to the synthesis of several key intermediates of chiral pharmaceuticals, including (S)-1-(2-chlorophenyl)ethanol, (S)-1-(2,4-difluorophenyl)ethanol and (S)-1-(2,6-difluorophenyl)ethanol, with 99% enantiomeric excess, and the conversion reached over 95% in a certain period of time. These results demonstrated the effectiveness of the strategy involving the fine-tuning of the substrate binding mode and the applicability of the designed mutants in efficient reduction of ortho-haloacetophenones.
- Li, Aipeng,Li, Xue,Pang, Wei,Tian, Qing,Wang, Ting,Zhang, Lianbing
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p. 2462 - 2472
(2020/05/13)
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- Redox-driven deracemization of secondary alcohols by sequential ether/O2-mediated oxidation and Ru-catalyzed asymmetric reduction
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The deracemization of benzylic alcohols has been achieved using a redox-driven one-pot two-step process. The racemic alcohols were oxidized by bis(methoxypropyl) ether and oxygen to give the ketone intermediates, followed by an asymmetric transfer hydrogenation with a chiral ruthenium catalyst. This compatible oxidation/reduction process gave the enantiomerically enriched alcohols with up to 95% ee values.
- Yang, Bing,Cui, Peng,Chen, Yongsheng,Liu, Qixing,Zhou, Haifeng
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- CO2-expanded liquids as solvents to enhance activity of Pseudozyma antarctica lipase B towards ortho-substituted 1-phenylethanols
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Pseudozyma (Candida) antarctica lipase B (CAL-B, Novozym 435) is one of the most widely used and outstanding biocatalysts. However, CAL-B-catalyzed transesterification of ortho-substituted 1-phenylethanol analogs suffers low conversion. In this research, the reactions were accelerated by using CO2-expanded liquids, liquids expanded by dissolving pressurized CO2, such as CO2-expanded hexane or CO2-expanded MeTHF.
- Hoang, Hai Nam,Koesoema, Afifa Ayu,Matsuda, Tomoko,Otsu, Moeko,Suzuki, Yuichi,Tamura, Mayumi
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supporting information
(2020/09/18)
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- SECONDARY ARYL ALCOHOL AND METHOD OF SYNTHESIZING THEREOF
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The present invention relates to secondary aryl alcohol and a method for synthesizing the same and, specifically, to synthesizing secondary aryl alcohol having high optical selectivity through a hydrosilylation reaction using ketone containing an aryl group. In the method for synthesizing secondary aryl alcohol according to an embodiment of the present invention, secondary aryl alcohol is synthesized by making ketone react with hydrosilane under a chiral boron Lewis acid catalyst.COPYRIGHT KIPO 2020
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Paragraph 0032; 0062-0069
(2020/05/13)
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- Thermoregulated ionic liquid-coordinating ruthenium complexes for asymmetric hydrogenation of aromatic ketones
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This work presented the synthesis and characterization of new ionic liquid-coordinating ruthenium complexes. The resulting ruthenium complexes exhibited not only excellent thermoregulated phase-separation behavior but also highly catalytic activity and enantioselectivity for the asymmetric hydrogenation with molecular hydrogen. The thermoregulated ionic liquid catalyst was highly resistant to leaching and was recycled consecutively for six times without significant loss of catalytic activity and enantioselectivity. The presence of Ru–H species revealed that NH and a Ru–H unit, involved in the hydride transfer process, were of great importance in the present catalytic system.
- Tang, Guoping,Chen, Manyu,Fang, Jian,Xu, Zichen,Gong, Honghui,Peng, Qingpo,Hou, Zhenshan
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- What to sacrifice? Fusions of cofactor regenerating enzymes with Baeyer-Villiger monooxygenases and alcohol dehydrogenases for self-sufficient redox biocatalysis
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A collection of fusion biocatalysts has been generated that can be used for self-sufficient oxygenations or ketone reductions. These biocatalysts were created by fusing a Baeyer-Villiger monooxygenase (cyclohexanone monooxygenase from Thermocrispum municipale: TmCHMO) or an alcohol dehydrogenase (alcohol dehydrogenase from Lactobacillus brevis: LbADH) with three different cofactor regeneration enzymes (formate dehydrogenase from Burkholderia stabilis: BsFDH; glucose dehydrogenase from Sulfolobus tokodaii: StGDH, and phosphite dehydrogenase from Pseudomonas stutzeri: PsPTDH). Their tolerance against various organic solvents, including a deep eutectic solvent, and their activity and selectivity with a variety of substrates have been studied. Excellent conversions and enantioselectivities were obtained, demonstrating that these engineered fusion enzymes can be used as biocatalysts for the synthesis of (chiral) valuable compounds.
- Mourelle-Insua, ángela,Aalbers, Friso S.,Lavandera, Iván,Gotor-Fernández, Vicente,Fraaije, Marco W.
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p. 1832 - 1839
(2019/02/24)
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- Enantiocomplementary decarboxylative hydroxylation combining photocatalysis and whole-cell biocatalysis in a one-pot cascade process
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Designing a green, highly efficient and stereoselective catalytic system to generate valuable enantioenriched products is a long-standing goal in green chemistry. Here, we report a one-pot cascade combining photocatalysts with (R)- or (S)-selective ketoreductases for the decarboxylative carbonylation of carboxylic acids and the subsequent bioreduction to generate valuable chiral alcohols. Using this approach, various chiral alcohols with complementary (R)- or (S)-configurations were prepared with good yields (up to 93%) and excellent stereoselectivity (up to 99% ee). Such a photochemo-enzymatic one-pot whole-cell process combines the advantages of both photocatalysts and enzyme catalysts and provides a mild, green, metal-free and highly stereoselective alternative in asymmetric decarboxylative hydroxylation reactions.
- Xu, Jian,Arkin, Mamatjan,Peng, Yongzhen,Xu, Weihua,Yu, Huilei,Lin, Xianfu,Wu, Qi
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supporting information
p. 1907 - 1911
(2019/04/27)
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- Chiral Frustrated Lewis Pairs Catalyzed Highly Enantioselective Hydrosilylations of Ketones
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A highly enantioselective Piers-type hydrosilylation of simple ketones was successfully realized using a chiral frustrated Lewis pair of tri-tert-butylphosphine and chiral diene-derived borane as catalyst. A wide range of optically active secondary alcohols were furnished in 80%—99% yields with 81%—97% ee's under mild reaction conditions.
- Liu, Xiaoqin,Wang, Qiaotian,Han, Caifang,Feng, Xiangqing,Du, Haifeng
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p. 663 - 666
(2019/05/21)
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- Chirality-Economy Catalysis: Asymmetric Transfer Hydrogenation of Ketones by Ru-Catalysts of Minimal Stereogenicity
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This manuscript describes the design and synthesis of Ru catalysts that feature only a single stereogenic element, yet this minimal chirality resource is demonstrated to be competent for effecting high levels of stereoinduction in the asymmetric transfer hydrogenation over a broad range of ketone substrates, including those that are not accommodated by known catalyst systems. The single stereogenic center of the (1-pyridine-2-yl)methanamine) is the only point-chirality in the catalysts, which simplifies this catalyst system relative to existing literature protocols.
- Chen, Fumin,He, Dongxu,Chen, Li,Chang, Xiaoyong,Wang, David Zhigang,Xu, Chen,Xing, Xiangyou
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p. 5562 - 5566
(2019/06/05)
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- Production of enantiomerically enriched chiral carbinols using Weissella paramesenteroides as a novel whole cell biocatalyst
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In this study, four bacterial strains were tested for their ability to reduce acetophenones to its corresponding alcohol. Among these strains Weissella paramesenteroides N7 was found to be the most successful biocatalyst to reduce the ketones to the corresponding alcohols. The reaction conditions were systematically optimized for W. paramesenteroides N7 that resulted in high enantioselectivity and conversion rates for the bioreduction. The scale-up asymmetric reduction of 1-(4-methoxyphenyl) propan-1-one (1r) by W. paramesenteroides N7 gave (R)-1-(4-methoxyphenyl) propan-1-ol (2r) with 94% yield and >99% enantiomeric excess. This is the first report showing the synthesis of (R)-1-(4-methoxyphenyl) propan-1-ol (2r) in enantiopure form using a biocatalyst on a gram scale. The whole cell catalyzed the reductions of ketone substrates on the preparative scale, demonstrating that W. paramesenteroides N7 would be a valuable biocatalyst for the preparation of chiral aromatic alcohols of pharmaceutical interest as a promising and alternative green approach.
- Tozlu, Caner,?ahin, Engin,Serencam, Hüseyin,Dertli, Enes
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p. 388 - 398
(2019/02/14)
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- Iridium-catalyzed asymmetric hydrogenation method for the preparation of chiral alcohols
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The present invention provides one kind of iridium-catalyzed asymmetric hydrogenation method for the preparation of chiral alcohols, the method specifically is: in the glove box filled with nitrogen, the [Ir (COD) Cl]2 With a chiral P, N, N ligand soluble in methanol, stir at room temperature 1 hour, [...] catalyst. Adding substrate alkone and alkali additive, is placed on the high-pressure in the reactor, for a certain reaction under the pressure of the hydrogenation reaction. Slowly release hydrogen, silica gel to remove the solvent and separate the product after the alcohol. The invention states iridium catalyzed alkone asymmetric hydrogenation for the preparation of chiral reaction has mild condition, easy to operate, and the product of the enantioselectivity and the like.
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Paragraph 0095-0103
(2019/06/07)
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- Synthesis of Enantiomerically Pure and Racemic Benzyl-Tethered Ru(II)/TsDPEN Complexes by Direct Arene Substitution: Further Complexes and Applications
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The use of a direct arene-exchange method for the synthesis of benzyl-tethered arene/Ru/TsDPEN complexes for use in asymmetric transfer hydrogenation is reported. A series of complexes tethered through a three-carbon linear chain was also prepared. The arene-exchange approach significantly simplifies the synthetic approach to this class of catalyst and permits the ready formation of modified analogues. The approach also provides a route to racemic catalysts for use in general reductions with either hydrogen or transfer hydrogenation.
- Soni, Rina,Jolley, Katherine E.,Gosiewska, Silvia,Clarkson, Guy J.,Fang, Zhijia,Hall, Thomas H.,Treloar, Ben N.,Knighton, Richard C.,Wills, Martin
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- Asymmetric transfer hydrogenation of acetophenone derivatives using 2-benzyl-tethered ruthenium (II)/TsDPEN complexes bearing η6-(p-OR) (R = H, iPr, Bn, Ph) ligands
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A series of 4′-OR (R = H, iPr, Bn, Ph) substituted ruthenium (II) biphenyl TsDPEN complexes are described; the complexes are accessed via an operationally simple and reliable two-step ligand synthesis followed by ligation to the ruthenium (II) centre. We report the preliminary asymmetric transfer hydrogenation (ATH) results on a range of primarily acetophenone derivatives with these new complexes using FA/TEA (5:2) as a reducing agent; the results confirm that these catalysts are capable of reducing the substrates within 48 h with excellent enantioselectivities.
- Knighton, Richard C.,Vyas, Vijyesh K.,Mailey, Luke H.,Bhanage, Bhalchandra M.,Wills, Martin
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- Immobilized and free cells of geotrichum candidum for asymmetric reduction of ketones: Stability and recyclability
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Marine-derived fungus Geotrichum candidum AS 2.361 was previously reported by our group as an active strain for the enantioselective reduction of ketones. Although some other Geotrichum strains were also found from the terrestrial sources, information on their stability and reusability is scarce. Herein, the stabilities—in terms of pH tolerance, thermostability, and storage stability, and reusability—of G. candidum AS 2.361 were described for the asymmetric reduction of a series of aromatic ketones. Two differently immobilized cells (agar immobilization and calcium alginate immobilization) as well as free cells were prepared. For three substrates (1-(3-bromophenyl) ethan-1-one (1b), 1-(2-chlorophenyl) ethan-1-one (1d), and acetophenone (1g)) immobilized cells on agar showed a great improvement in the bioreduction activities compared to the free cells, increasing yields up to 97% with ee values of 99%. Cells immobilized on agar/calcium alginate could maintain more than 90% of the original activities within the assayed pH ranges of 3.5–11, while free cells were highly sensitive to alkaline and acidic conditions. Concerning thermostability, immobilized cells on agar kept 99% of their original activities after incubation at 60?C for 1 h, while almost no activity was detected for the free cells under the same condition. Immobilized cells were stable at 4?C for 80 days without any activity loss, while free cells started to decrease the activity after storage at 4?C for six days. The immobilized cells retained almost 99% activity after four reuse cycles, while free cells lost almost all the activities at on the third cycle.
- Liu, Hui,de Souza, Fayene Zeferino Ribeiro,Liu, Lan,Chen, Bi-Shuang
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- Ir-catalyzed asymmetric hydrogenation of simple ketones with chiral ferrocenyl P,N,N-ligands
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The Ir-catalyzed asymmetric hydrogenation of simple aromatic ketones with chiral ferrocenyl P,N,N-ligands has been developed. Under the optimized conditions, a wide range of ketones were hydrogenated to afford the corresponding chiral alcohols in good to excellent enantioselectivities (up to 98% ee).
- Qin, Chao,Hou, Chuan-Jin,Liu, Hongzhu,Liu, Yan-Jun,Huang, De-Zhi,Hu, Xiang-Ping
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supporting information
p. 719 - 722
(2018/01/17)
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- Enantioselective Reduction of Ketones Catalyzed by Rare-Earth Metals Complexed with Phenoxy Modified Chiral Prolinols
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Enantioselective reduction of ketones and α,β-unsaturated ketones by pinacolborane (HBpin) has been well-established by using chiral rare-earth metal catalysts with phenoxy modified prolinols. A number of highly optically active alcohols were obtained from reduction of simple ketones catalyzed by ytterbium complex 1 [L4Yb(L4H)] (H2L4 = (S)-2- tert-butyl-6-((2-(hydroxydiphenylmethyl)pyrrolidin-1-yl)methyl)phenol). Moreover, α,β-unsaturated ketones were selectively reduced to a wide range of chiral allylic alcohols with excellent yields, high enantioselectivity, and complete chemoselectivity, catalyzed by a single component chiral ytterbium complex 2 [L1Yb(L1H)] (H2L1 = (S)-2,4-di-tert-butyl-6-((2-(hydroxydiphenylmethyl)pyrrolidin-1-yl)methyl)phenol).
- Song, Peng,Lu, Chengrong,Fei, Zenghui,Zhao, Bei,Yao, Yingming
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p. 6093 - 6100
(2018/05/23)
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- N,O- vs N,C-Chelation in Half-Sandwich Iridium Complexes: A Dramatic Effect on Enantioselectivity in Asymmetric Transfer Hydrogenation of Ketones
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Cyclometalation of [Cp?IrCl2]2 with methyl (S)-2-phenyl-4,5-dihydrooxazole-4-carboxylate in the presence of NaOAc selectively led to a N,C- or N,O-chelated Cp?Ir(III) complex, depending on whether or not water was present in the reaction. While derived from the same precursor, these two complexes behaved in a dramatically different manner in asymmetric transfer hydrogenation (ATH) of ketones by formic acid, with the N,O-chelated complex being much more selective and active. The sense of asymmetric induction is also different, with the N,O-complex affording S while the N,C-analogue R alcohols. Further study revealed that the nature of the base additive considerably impacts the enantioselectivity and the effective HCOOH/amine ratios. These observations show the importance of ligand coordination mode and using the right base for ATH reactions.
- Zhou, Gang,Aboo, Ahmed H.,Robertson, Craig M.,Liu, Ruixia,Li, Zhenhua,Luzyanin, Konstantin,Berry, Neil G.,Chen, Weiping,Xiao, Jianliang
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p. 8020 - 8026
(2018/09/06)
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- Tridentate nitrogen phosphine ligand and complex and application thereof in asymmetric catalytic hydrogenation of ketone
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The invention belongs to the field of organic and medicine synthetic chemistry, and discloses a tridentate nitrogen phosphine ligand. The tridentate nitrogen phosphine ligand has a structure shown ina formula I which is shown in the attached figure, wherein R1 is toluene sulfonyl or 2,4,6-triisopropylbenzenesulfonyl, and R2 is aryl or substituted aryl. The invention also discloses a complex of the tridentate nitrogen phosphine ligand; the complex is prepared by mixing the tridentate nitrogen phosphine ligand and a transition metal complex; the complex is used for asymmetric catalytic hydrogenation of ketone. The tridentate nitrogen phosphine ligand has the advantages that 1, the synthesizing is easy, and the chiral ligand can be prepared by only two to three reaction steps; 2, the ligandis stable, the series of ligand is not sensitive to water and oxygen, and the convenience in storage and use is realized; 3, the catalyzing effect is good, and the catalyst can be used for realizing 100% of conversion and 99% of stereo selectivity on most of suitable primers; 4, the atom economy is high, and the activity of the catalysis system is higher; for most of suitable primers, the conversion number reaches more than 10000, and the maximum conversion number reaches 200000.
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Paragraph 0087; 0088; 0089; 0090
(2018/04/03)
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- Scope and Mechanism on Iridium-f-Amphamide Catalyzed Asymmetric Hydrogenation of Ketones
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A series of novel and easily accessed ferrocene-based amino-phosphine-sulfonamide (f-Amphamide) ligands have been developed and applied in Ir-catalyzed asymmetric hydrogenation of aryl ketones, affording the corresponding chiral secondary alcohols with excellent results (up to >99% conversion, >99% ee and TON up to 200 000). DFT calculations suggest an activating model involving an alkali cation Li+.
- Liang, Zhiqin,Yang, Tilong,Gu, Guoxian,Dang, Li,Zhang, Xumu
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p. 851 - 856
(2018/07/31)
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- Method for direct conversion of aromatic alkyne into chiral alcohol through one-pot process
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The invention relates to a method for direct conversion of aromatic alkyne into chiral alcohol through a one-pot process. The method uses cheap and easily-available alkyne I as a raw material, adoptsa two-step one-pot strategy for direct synthesis of chiral alcohol II, and comprises the following concrete steps: step 1) with fluorine-containing alcohol and water as solvents, allowing the alkyne Ito generate a hydration reaction under the catalysis of trifluoromethanesulfonic acid so as to generate an intermediate namely ketone; and step 2) directly adding a complex of monossulfonyl chiral diamine and metal ruthenium or rhodium or iridium as a catalyst into a reaction system, and with a mixture of a sodium formate aqueous solution or formic acid-triethylamine as a hydrogen source, carrying out an asymmetric transfer hydrogenation reaction so as to obtain a product II. The method provided by the invention has the following advantages: operation is simple and convenient; reaction conditions are mild; and a substrate has wide application range and high enantioselectivity. Concretely, the method provided by the invention has a general reaction formula which is described in the specification.
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Paragraph 0056; 0057; 0058
(2018/06/26)
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- Iridium-Catalyzed Asymmetric Hydrogenation of Ketones with Accessible and Modular Ferrocene-Based Amino-phosphine Acid (f-Ampha) Ligands
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A series of tridentate ferrocene-based amino-phosphine acid (f-Ampha) ligands have been successfully developed. The f-Ampha ligands are extremely air stable and exhibited excellent performance in the Ir-catalyzed asymmetric hydrogenation of ketones (full conversions, up to >99% ee, and 500?000 TON). DFT calculations were performed to elucidate the reaction mechanism and the importance of the COOH group. Control experiments also revealed that the COOH group played a key role in this reaction.
- Yu, Jianfei,Long, Jiao,Yang, Yuhong,Wu, Weilong,Xue, Peng,Chung, Lung Wa,Dong, Xiu-Qin,Zhang, Xumu
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supporting information
p. 690 - 693
(2017/02/10)
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- Highly Enantioselective Hydrosilylation of Ketones Catalyzed by a Chiral Oxazaborolidinium Ion
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A highly enantioselective hydrosilylation of ketones was developed for the synthesis of a variety of chiral secondary alcohols. In the presence of a chiral oxazaborolidinium ion (COBI) catalyst, the reaction proceeded with good yields (up to 99%) with excellent enantioselectivities (up to 99% ee).
- Kang, Byung Chul,Shin, Sung Ho,Yun, Jaesook,Ryu, Do Hyun
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supporting information
p. 6316 - 6319
(2017/12/08)
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- Debaryomyces hansenii as a new biocatalyst in the asymmetric reduction of substituted acetophenones
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Chiral secondary alcohols are convenient mediator for the synthesis of biologically active compounds and natural products. In this study fifteen yeast strains belonging to three food originated yeast species Debaryomyces hansenii, Saccharomyces cerevisiae and Hanseniaspora guilliermondii were tested for their capability for the asymmetric reduction of acetophenone to 1-phenylethanol as biocatalyst microorganisms. Of these strains, Debaryomyces hansenii P1 strain showed an effective asymmetric reduction ability. Under optimized conditions, substituted acetophenones were converted to the corresponding optically active secondary alcohols in up to 99% enantiomeric excess and at high conversion rates. This is the first report on the enantioselective reduction of acetophenone by D. hansenii P1 from past?rma, a fermented Turkish meat product. The preparative scale asymmetric bio reduction of 3-methoxy acetophenone 1g by D. hansenii P1 gave (R)-1-(3-methoxyphenyl) ethanol 2g 82% yield, and >99% enantiomeric excess. Compound 2g can be used for the synthesis of (+)-NPS-R-568 [3-(2-chlorophenyl)-N-[(1R)-1-(3-methoxyphenly) ethyl] propan-1-amine] which have a great potential for the treatment of primary and secondary hyper-parathyroidism. In addition, D. hansenii P1 successfully reduced acetophenone derivatives. This study showed that this yeast can be used industrially to produce enantiomerically pure chiral secondary alcohols, which can be easily converted to different functional groups.
- ?ahin, Engin
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p. 363 - 371
(2017/09/13)
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- Readily Accessible and Highly Efficient Ferrocene-Based Amino-Phosphine-Alcohol (f-Amphol) Ligands for Iridium-Catalyzed Asymmetric Hydrogenation of Simple Ketones
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We have successfully developed a series of novel and modular ferrorence-based amino-phosphine-alcohol (f-Amphol) ligands, and applied them to iridium-catalyzed asymmetric hydrogenation of various simple ketones to afford the corresponding chiral alcohols with excellent enantioselectivities and conversions (98–99.9 % ee, >99 % conversion, turnover number up to 200 000). Control experiments and density functional theory (DFT) calculations have shown that the hydroxyl group of our f-Amphol ligands played a key role in this asymmetric hydrogenation.
- Yu, Jianfei,Duan, Meng,Wu, Weilong,Qi, Xiaotian,Xue, Peng,Lan, Yu,Dong, Xiu-Qin,Zhang, Xumu
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supporting information
p. 970 - 975
(2017/02/05)
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- Highly Enantioselective Production of Chiral Secondary Alcohols with Candida zeylanoides as a New Whole Cell Biocatalyst
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The increasing demand for biocatalysts in synthesizing enantiomerically pure chiral alcohols results from the outstanding characteristics of biocatalysts in reaction, economic, and ecological issues. Herein, fifteen yeast strains belonging to three food originated yeast species Candida zeylanoides, Pichia fermentans, and Saccharomyces uvarum were tested for their capability for asymmetric reduction of acetophenone to 1-phenylethanol as biocatalysts. Of these strains, C.?zeylanoides P1 showed an effective asymmetric reduction ability. Under optimized conditions, substituted acetophenones were converted to corresponding optically active secondary alcohols in up to 99% enantiomeric excess and at high yields. The preparative scale asymmetric bioreduction of 4-nitroacetophenone (1m) by C.?zeylanoides P1 gave (S)-1-(4-nitrophenyl)ethanol (2m) with 89% yield and >?99% enantiomeric excess. Compound 2m has been obtained in an enantiomerically pure and inexpensive form. Additionally, these results indicate that C.?zeylanoides P1 is a promising biocatalyst for the synthesis of chiral alcohols in industry.
- ?ahin, Engin,Dertli, Enes
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- NHTs Effect on the Enantioselectivity of Ru(II) Complex Catalysts Bearing a Chiral Bis(NHTs)-Substituted Imidazolyl-Oxazolinyl-Pyridine Ligand for Asymmetric Transfer Hydrogenation of Ketones
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Pincer-type ruthenium(II)-NNN complex catalysts bearing a chiral bis(NHTs)-substituted imidazolyl-oxazolinyl-pyridine ligand were synthesized and structurally characterized by NMR, IR, elemental analysis, and X-ray single-crystal crystallographic determinations. The two NHTs groups substituted on the imidazolyl moiety of the chiral NNN ligand exhibited a remarkable effect on the enantioselectivity of the Ru(II)-NNN complexes for the asymmetric transfer hydrogenation (ATH) of ketones. The Ru(II)-NNN complex bearing a chiral (NHTs)2-substituted imidazolyl-(isopropyl)oxazolinyl-pyridine ligand exhibited excellent catalytic activity, reaching an enantioselectivity up to 99.9% ee for the target alcohol products.
- Chai, Huining,Liu, Tingting,Yu, Zhengkun
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p. 4136 - 4144
(2017/11/21)
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- Asymmetric Transfer Hydrogenation of Ketones Using New Iron(II) (P-NH-N-P′) Catalysts: Changing the Steric and Electronic Properties at Phosphorus P′
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The asymmetric transfer hydrogenation (ATH) of ketones is an efficient method for producing enantio-enriched alcohols which are used as intermediates in a variety of industrial processes. Here we report the synthesis of new iron ATH precatalysts (S,S)-[FeBr(CO)(Ph2PCH2CH2NHCHPhCHPhNC=CHCH2PR′2)][BPh4] (R′=Et, and ortho-tolyl (o-Tol)) where one of the phosphine groups is modified with small alkyl and large aryl substituents to probe the effect of this change on the activity and selectivity of the catalytic system. A simple reversible equilibrium kinetic model is used to obtain the initial TOF and the inherent enantioselectivity S=kR/kS of these catalysts along with those for the previously reported catalysts with R′=Ph and Cy for the ATH of acetophenone. With an increase in the size of the PR′2 group, the TOF goes through a maximum at PPh2 while the S value goes through a maximum of 510 at R′=Cy. The complex with R′=o-Tol starts with a high S value of 200 but is rapidly changed to a second catalyst with an S value of 28. For the reduction of acetophenone to (R)-1-phenylethanol, turnover numbers of up to 5200 and ee up to 98 % were achieved. The chemotherapeutic pharmaceutical precursor (R)-(3′,5′-bis(trifluoromethyl))-1-phenylethanol is synthesized in up to 95 % ee. Several other alcohols can be prepared in greater than 90 % ee by choosing the precatalyst with the correctly matched steric properties. A hydride complex derived from the catalyst with R′=Cy is characterized by NMR spectroscopy. It is proposed that low concentration trans-hydride carbonyl complexes with the FeH parallel to the NH of the ligand are the active catalysts in all of these systems.
- Smith, Samantha A. M.,Prokopchuk, Demyan E.,Morris, Robert H.
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p. 1204 - 1215
(2017/09/06)
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- Dinuclear zinc complex catalyzed asymmetric methylation and alkynylation of aromatic aldehydes
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A general AzePhenol dinuclear zinc catalytic system has been successfully developed and introduced into the asymmetric addition of dimethylzinc and alkynylzinc to aromatic aldehydes. In this system, an azetidine derived chiral ligand has proven to be an effective enantioselective promoter. Under the optimal reaction conditions, a series of chiral 1-hydroxyethyl (up to 99% ee) and secondary propargylic alcohols (up to 96% ee) were generated with good yields and enantioselectivities. Additionally, this novel catalytic system showed good functional group compatibility. Remarkably, the substituent's electronic nature alone is not sufficient to allow for exclusive enantioselectivity, an additional substituent's location also had an effect. We proposed that the formation of a stable and structural rigid transition state by the chelation of ortho substituted benzaldehydes to the zinc atom was responsible for the observed higher enantioselectivity. The possible catalytic cycles of both transformations accounting for the stereoselectivity were described accordingly.
- Liu, Shanshan,Li, Gao-Wei,Yang, Xiao-Chao,Zhang, De-Yang,Wang, Min-Can
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p. 7147 - 7156
(2017/09/07)
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- Highly Enantioselective Production of Chiral Secondary Alcohols Using Lactobacillus paracasei BD101 as a New Whole Cell Biocatalyst and Evaluation of Their Antimicrobial Effects
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Chiral secondary alcohols are valuable intermediates for many important enantiopure pharmaceuticals and biologically active molecules. In this work, we studied asymmetric reduction of aromatic ketones to produce the corresponding chiral secondary alcohols using lactic acid bacteria (LAB) as new biocatalysts. Seven LAB strains were screened for their ability to reduce acetophenones to their corresponding alcohols. Among these strains, Lactobacillus paracasei BD101 was found to be the most successful at reducing the ketones to the corresponding alcohols. The reaction conditions were further systematically optimized for this strain and high enantioselectivity (99%) and very good yields were obtained. These secondary alcohols were further tested for their antimicrobial activities against important pathogens and significant levels of antimicrobial activities were observed although these activities were altered depending on the secondary alcohols as well as their enantiomeric properties. The current methodology demonstrates a promising and alternative green approach for the synthesis of chiral secondary alcohols of biological importance in a cheap, mild, and environmentally useful process.
- Y?lmaz, Durmu?han,?ahin, Engin,Dertli, Enes
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- Unsymmetrical Iron P-NH-P′ Catalysts for the Asymmetric Pressure Hydrogenation of Aryl Ketones
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The reductive amination of α-dialkylphosphine acetaldehydes with enantiopure β-aminophosphines is a new, versatile route to unsymmetrical tridentate (pincer) ligands P-NH-P′. Four new ligands PR2CH2CH2NHCHR′CHR′′PPh2 (R=iPr, Cy, R′=Ph, CH(CH3)2, R′′=Ph, H) prepared in this way are used to make the iron(II) complexes mer-FeCl2(CO)(P-NH-P′) and mer-FeCl(H)(CO)(P-NH-P′). The hydride complex with the rigid ligand with R′=R′′=Ph is an efficient and highly enantioselective homogeneous asymmetric pressure hydrogenation (APH) catalyst. Prochiral aryl ketones are reduced under mild conditions (THF, 0.1 mol % catalyst, 1 mol % KOtBu, 5–10 bar, 50 °C) to the (S)-alcohols, usually in enantiomeric excess (ee) greater than 90 %. DFT calculations provided transition-state structures for the enantiodetermining hydride-transfer step.
- Smith, Samantha A. M.,Lagaditis, Paraskevi O.,Lüpke, Anne,Lough, Alan J.,Morris, Robert H.
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p. 7212 - 7216
(2017/05/31)
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- Alternatives to Phosphinooxazoline (t-BuPHOX) Ligands in the Metal-Catalyzed Hydrogenation of Minimally Functionalized Olefins and Cyclic β-Enamides
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This study presents a new series of readily accessible iridium- and rhodium-phosphite/oxazoline catalytic systems that can efficiently hydrogenate, for the first time, both minimally functionalized olefins and functionalized olefins (62 examples in total) in high enantioselectivities (ees up to >99%) and conversions. The phosphite-oxazoline ligands, which are readily available in only two synthetic steps, are derived from previous privileged 4-alkyl-2-[2-(diphenylphosphino)phenyl]-2-oxazoline (PHOX) ligands by replacing the phosphine moiety by a biaryl phosphite group and/or the introduction of a methylene spacer between the oxazoline and the phenyl ring. The modular design of the ligands has given us the opportunity not only to overcome the limitations of the iridium-PHOX catalytic systems in the hydrogenation of minimally functionalized Z-olefins and 1,1-disubstituted olefins, but also to expand their use to unfunctionalized olefins containing other challenging scaffolds (e.g., exocyclic benzofused and triaryl-substituted olefins) and also to olefins with poorly coordinative groups (e.g., α,β-unsaturated lactams, lactones, alkenylboronic esters, etc.) with enantioselectivities typically >95% ee. Moreover, both enantiomers of the hydrogenation product could be obtained by simply changing the configuration of the biaryl phosphite moiety. Remarkably, the new catalytic systems also provided excellent enantioselectivities (up to 99% ee) in the asymmetric hydrogenation of another challenging class of olefins – the functionalized cyclic β-enamides. Again, both enantiomers of the reduced amides could be obtained by changing the metal from Ir to Rh. We also demonstrated that environmentally friendly propylene carbonate can be used with no loss of enantioselectivity. Another advantage of the new ligands over the PHOX ligands is that the best ligands are derived from the affordable (S)-phenylglycinol rather than from the expensive (S)-tert-leucinol. (Figure presented.).
- Biosca, Maria,Magre, Marc,Coll, Mercè,Pàmies, Oscar,Diéguez, Montserrat
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supporting information
p. 2801 - 2814
(2017/08/23)
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- Manganese complex-catalyzed oxidation and oxidative kinetic resolution of secondary alcohols by hydrogen peroxide
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The highly efficient catalytic oxidation and oxidative kinetic resolution (OKR) of secondary alcohols has been achieved using a synthetic manganese catalyst with low loading and hydrogen peroxide as an environmentally benign oxidant in the presence of a small amount of sulfuric acid as an additive. The product yields were high (up to 93%) for alcohol oxidation and the enantioselectivity was excellent (>90% ee) for the OKR of secondary alcohols. Mechanistic studies revealed that alcohol oxidation occurs via hydrogen atom (H-atom) abstraction from an α-CH bond of the alcohol substrate and a two-electron process by an electrophilic Mn-oxo species. Density functional theory calculations revealed the difference in reaction energy barriers for H-atom abstraction from the α-CH bonds of R- and S-enantiomers by a chiral high-valent manganese-oxo complex, supporting the experimental result from the OKR of secondary alcohols.
- Miao, Chengxia,Li, Xiao-Xi,Lee, Yong-Min,Xia, Chungu,Wang, Yong,Nam, Wonwoo,Sun, Wei
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p. 7476 - 7482
(2017/10/30)
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- Chiral tridentate phosphonic amine ligand and application thereof in asymmetric catalytic reaction
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The invention relates to a chiral tridentate phosphonic amine ligand and application thereof in an asymmetric catalytic reaction. The novel chiral tridentate phosphonic amine ligand disclosed by the invention is a first case of tridentate phosphonic amine ligand containing ferrocenyl chiral phosphine at present and is successfully applied to high-efficiency and high-selectivity asymmetric hydrogenation and similar reaction thereof for simple aromatic ketone and aliphatic ketone. The type of ligand has the advantages of simple synthetic route, low cost, easiness in large-scale synthesis and stable air; the chiral tridentate phosphonic amine ligand shows high activity and high selectivity for asymmetric hydrogenation reaction of carbon-oxygen double bond, and has a broad industrial application prospect.
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Paragraph 0080; 0081; 0082
(2017/08/29)
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- Highly Enantioselective Transfer Hydrogenation of Polar Double Bonds by Macrocyclic Iron(II)/(NH)2P2 Catalysts
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We describe herein a new protocol for the synthesis of 2,2′-((1S,1′S)-ethane-1,2-diylbis(phenylphosphanediyl))dibenzaldehyde ((SP,SP)-5), which is the key intermediate in the synthesis of macrocyclic iron(II)/(NH)2P2 catalysts for the highly enantioselective transfer hydrogenation of polar double bonds. The dialdehyde (SP,SP)-5 was obtained as a single diastereoisomer and enantiomer from an optically pure H-phosphinate in 33% yield over five steps. It was further converted to afford multigram quantities of the macrocyclic iron(II)/(NH)2P2 complexes, which were tested in the asymmetric transfer hydrogenation of aryl alkyl ketones and imines in 2-propanol on a 100 mmol scale. Ten substrates, including challenging ones such as tert-butyl phenyl ketone and industrially relevant molecules such as 3,5-bis(trifluoromethyl)acetophenone, were reduced in high yield (89.0-99.7%), excellent enantioselectivity (95.8-99.4% ee), and with low catalyst loadings (S/C up to 10 000/1).
- Bigler, Raphael,Mezzetti, Antonio
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supporting information
p. 253 - 261
(2016/03/04)
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- Iridium Catalysts with f-Amphox Ligands: Asymmetric Hydrogenation of Simple Ketones
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A series of modular and rich electronic tridentate ferrocene aminophosphoxazoline ligands (f-amphox) have been successfully developed and used in iridium-catalytic asymmetric hydrogenation of simple ketones to afford corresponding enantiomerically enriched alcohols under mild conditions with superb activities and excellent enantioselectivities (up to 1"000"000 TON, almost all products up to >99% ee, full conversion). The resulting chiral alcohols and their derivatives are important intermediates in pharmaceuticals.
- Wu, Weilong,Liu, Shaodong,Duan, Meng,Tan, Xuefeng,Chen, Caiyou,Xie, Yun,Lan, Yu,Dong, Xiu-Qin,Zhang, Xumu
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supporting information
p. 2938 - 2941
(2016/07/06)
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