- A model for the enatioselective hydrogenation of pyruvate catalysed by alkaloid-modified platinum
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A LEED and XPS study of the adsorption of naphthalene, quinoline, and 10,11-dihydrocinchonidine on Pt(111) at 300K has shown that only naphthalene forms an ordered ad-layer, and that quinoline and the alkaloid adsorb in a disordered state and without decomposition.These experiments do not support the hypothesis of ordered adsorption of alkaloid that forms the basis of the template model for the interpretation of enantioselectivity in Pt-catalysed pyruvate hydrogenation.The model is accordingly reviewed.Molecular modelling studies show that a highly specific 1:1 interaction between cinchonidine (or cinchonine) and pyruvate interprets the observed sense of the enantioselectivity, provided relative energy relationships derived for purely intermolecular interactions are valid for the same molecules in the absorbed state.Moreover, the 'product' of this 1:1 interaction is a satisfactory precursor to the H-bonded state considered responsible for the greatly enhanced rate that always accompanies enantioselective reaction over cinchona-modified Pt.The previously published dependencies of optical yield on (a) surface concentration of adsorbed cinchonidine modifier, and (b) modifier composition for mixtures of quinine and quinidine, are shown to be in quantitative agreement with the proposed 1:1 interaction model and at variance with the ordered adsorption model.Catalysts modified and used under strictly anaerobic conditions show negligible activity and enantioselectivity demonstrating that oxygen plays a crucial role in successful catalyst preparation.XPS experiments confirm that adsorption of cinchonidine from air-saturated ethanolic solution on Pt(111) provides an adlayer containing both alkaloid and adsorbed oxygen. (S)-(-)-1-benzyl-pyrrolidine-2-methanol, various configurations of ephedrine, D- and L-histidine and the methyl esters of D- and L-tryptophan have been examined as modifiers for supported Pt.Although there is evidence that these compounds can provide chiral direction to pyruvate hydrogenation, rate enhancement is slight and enantioselectivity is correspondingly low.
- Simons, K. E.,Meheux, P. A.,Griffiths, S. P.,Sutherland, I. M.,Johnston, P.,et al.
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- Chirally modified platinum nanoparticles stabilized by dendritic core-multishell architectures for the asymmetric hydrogenation of ethyl pyruvate
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In this paper we present the asymmetric hydrogenation of α-keto esters with platinum nanoparticles homogeneously stabilized in dendritic coremultishell architectures. The main focus lies on recycling and metal leaching, because little is reported so far a
- Keilitz, Juliane,Nowag, Sabrina,Marty, Jean-Daniel,Haag, Rainer
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- High enantioselectivity in the asymmetric hydrogenation of ketones by a supported Pt nanocatalyst on a mesoporous modified MCM-41 support
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Catalysts containing metal nanotubes were prepared by the adsorption of platinum metal nanotubes onto functionalized and modified silica surfaces (MCM-41 and fumed silica). (3-Chloropropyl)trimethoxysilane and cinchonidine were used for functionalization and modification, respectively. Potassium chloroplatinate was used as the metal precursor to impregnate platinum metal nanotubes on the pretreated functionalized and modified silica surfaces. The solid catalysts were characterized by ESEM, TEM, EDAX, and XPS. The MCM-41 supported platinum nanotube catalyst showed >98% to ~100% enantioselectivity towards the hydrogenation of a range of pharmaceutically important chemicals such as methyl pyruvate, ethyl pyruvate, and acetophenone with nearly full conversion.
- Basu, Susmit
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- Platinum functionalized multiwall carbon nanotube composites as recyclable catalyst for highly efficient asymmetric hydrogenation of methyl pyruvate
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Platinum functionalized carbon materials such as carbon fibres, graphene, MWNTs (multiwalled carbon nanotubes) and activated carbon were used as heterogeneous catalytic systems for asymmetric hydrogenation of α-ketoester i.e. methyl pyruvate using cinchonidine (CD) as a chiral modifier. Interestingly, the MWNTs exhibited excellent enantioselectivity (>99% ee) and conversion (99%) in comparison to other Pt/C systems due to their high surface area. Furthermore, in the case of Pt/MWNTs, Pt nanoparticles are found to be uniformly dispersed and bound to the MWNTs acting like a single atom catalyst. Time-dependent nuclear magnetic resonance (NMR) studies, cyclic voltammetry (CV) and diffuse reflectance spectroscopy (DRS) have been carried out to study substrate-modifier-catalyst interactions. Recyclability of the catalyst was also tested up to ten cycles without losing any significant catalytic activity.
- Sharma, Poonam,Sharma, Rakesh K.
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p. 102481 - 102487
(2015)
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- Asymmetric hydrogenation of α-ketoesters over finely dispersed polymer-stabilized platinum clusters
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Finely dispersed polyvinylpyrrolidone-stabilized platinum clusters (PVP-Pt) modified with cinchonidine catalyze the asymmetric hydrogenation of α-ketoesters, giving enantiomeric excesses in favour of R-(+)-methyl lactate up to 97.6%. The reaction is demonstrated to be structure insensitive and runs best over a tiny cluster with a mean size of 1.4 nm, which is quite different from conventional supported catalysts.
- Zuo, Xiaobin,Liu, Hanfan,Liu, Manhong
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- Enantioselective Hydrogenation. III. Methyl Pyruvate Hydrogenation Catalyzed by Alkaloid-Modified Iridium
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Enantioselective hydrogenation of methyl pyruvate, MeCOCOOMe to methyl lactate, MeCH(OH)COOMe, is catalyzed in solution at room temperature by supported iridium catalysts modified with cinchona alkaloids.Modification with cinchonidine or quinine yields R-lactate in excess, whereas modification with cinchonine or quinidine favors S-lactate formation.Ir/SiO2 catalysts (20percent) calcined at 393 to 573 K and reduced at 523 to 593 K were highly active for racemic hydrogenation in the absence of a modifier (rates typically 1.8 mol h-1 gcat-1) and were comparably active when modified with cinchonidine but gave an enantiomeric excess of about 30percent.Use of higher calcination or reduction temperatures led to substantially inferior activity and selectivity.The high rates recorded for both racemic and enantioselective reactions are dependent on the catalysts being activated before use by a procedure involving exposure of the catalyst to air after the initial reduction.Use of a Cl-free precursor gave an Ir/SiO2 catalyst (20percent) of superior activity but inferior enantioselectivity.Ir/CaCO3 (5percent) was more active for racemic hydrogenation than for enantioselective hydrogenation, but provided the highest value of the enantiomeric excess 39percent.Kinetics of reaction are reported.Exchange of H for D in 10,11-dihydrocinchonidine at room temperature over Ir/CaCO3 occurred in the quinoline moiety byt not in the quinuclidine ring system, indicating that the alkaloid was adsorbed to the Ir surface via the interaction of its ?-electron system.For both silica-supported and calcium carbonate-supported Ir, the presence of chloride ion in the catalyst was advantageous for the achievement of enantioselectivity.
- Simons, K. E.,Ibbotson, A.,Johnston, P.,Plum, H.,Wells, P. B.
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- Synthesis of alkyl (R)-lactates and alkyl (S,S)-O-lactyllactates by alcoholysis of rac-lactide using Novozym 435
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Enzymatic alcoholysis of rac-lactide for kinetic resolution was carried out in organic solvents. Effects of organic solvent, reaction temperature, and alcohol as a nucleophile were also investigated in Novozym 435-catalyzed alcoholysis of rac-lactide. Both alkyl (R)-lactate and alkyl (S,S)-O-lactyllactate were simultaneously obtained in high yields (>45%) and high enantiopurities (>97% ee) through Novozym 435-catalyzed ring-opening of rac-lactide and subsequent enantioselective alcoholysis of the resultant alkyl O-lactyllactate.
- Jeon, Nan Young,Ko, Sung-Jin,Won, Keehoon,Kang, Han-Young,Kim, Bum Tae,Lee, Yeon Soo,Lee, Hyuk
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- Carbonyl Cluster Derived Polystyrene Supported Platinum for Asymmetric Hydrogenation of α-Ketoesters
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Ion-pairing of anionic carbonyl clusters with cinchona alkaloid groups on cross-linked polystyrene is a viable method for the synthesis of asymmetric catalysts for the hydrogenation of methyl pyruvate.
- Bhaduri, Sumit,Darshane, Vishnu S.,Sharma, Krishna,Mukesh, Doble
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- New insights into the relationship between conversion and enantioselectivity for the asymmetric hydrogenation of alkyl pyruvate
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The initial transient period in the enantioselective hydrogenation of alkyl pyruvate esters is probed using the sequential reactions of ethyl and methyl pyruvate. The reaction of methyl pyruvate, subsequent to the hydrogenation of ethyl pyruvate, led to a higher e.e. when compared to the coreaction of these reactants, or prehydrogenation with methyl pyruvate followed by reaction of ethyl pyruvate. The initial transient effect, in which e.e. increases with conversion, is observed in both periods of the sequential reaction and the origin of this effect is discussed.
- Li, Xiabao,Wells, Richard P.K.,Wells, Peter B.,Hutchings, Graham J.
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- Solvent and substituent effects on the sense of the enantioselective hydrogenation of pyruvate esters catalysed by Pd and Pt in colloidal and supported forms
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The outcome of the enantioselective hydrogenation of pyruvate esters using cinchona alkaloid-modified palladium catalysts is dependent on the choice of solvent/substituent; the sense of the enantioselectivity can be switched from S to R whilst maintaining the magnitude of the enantiomeric excess.
- Collier, Paul J.,Hall, Tracey J.,Iggo, Jonathan A.,Johnston, Peter,Slipszenko, J. Anton,Wells, Peter B.,Whyman, Robin
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- New diphosphinite ligands derived from mannitol for rhodium catalyzed enantioselective hydrogenation of ketones
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We have developed new electron rich chiral bisphosphinites from mannitol. The new ligands have been found to be efficient chiral auxiliaries for rhodium catalyzed hydrogenation of functionalized ketones leading to hydroxy compounds in up to 86% ee. (C) 2000 Elsevier Science Ltd.
- Naili, Said,Suisse, Isabelle,Mortreux, André,Agbossou, Francine,Ait Ali, Mustapha,Karim, Abdallah
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- Novel Alkaloid Modifiers for Enantioselective Heterogeneous Catalysis
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The alkaloids codeine, 7,8-dihydrocodeine, brucine and strychnine, when adsorbed on Pt/silica (EUROPT-1) induce enantioselectivity and enhance the rate of hydrogenation of the carbonyl function in methyl pyruvate and in butane-2,3-dione.
- Griffiths, Stephen P.,Johnston, Peter,Vermeer, Wilhelmus A. H.,Wells, Peter B.
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- Enhancing Effect of Residual Capping Agents in Heterogeneous Enantioselective Hydrogenation of α-keto Esters over Polymer-Capped Pt/Al2O3
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Heterogeneous enantioselective catalysis is considered a promising strategy for the large-scale production of enantiopure chemicals. In this work, polymer-capped Pt nanocatalysts having a uniform size were synthesized using poly(vinyl pyrrolidone) (PVP) and poly(vinyl alcohol) and supported on γ-Al2O3. After a facile heat treatment process, their catalytic performance for enantioselective hydrogenation of α-keto esters, a structure-sensitive reaction, was investigated. The presence of residual capping agents on the Pt surface often perturbs the adsorption of reacting species and reduces performance in structure-sensitive reactions. However, the 1 wt % PVP-Pt/Al2O3 catalyst exhibited an enhancement in both activity and enantioselectivity compared to a reference Pt/Al2O3 catalyst prepared by wet impregnation. Under optimized reaction conditions, the cinchonidine-modified PVP-Pt/Al2O3 gave an enantiomeric excess of 95% for the enantioselective hydrogenation of methyl pyruvate despite the low Pt loading. We demonstrate that depending on the type of polymers, the residual capping agents can lead to site-selective blockage of the Pt surface, that is, defects or terraces. Quantitative and qualitative analyses also show that the noticeable improvement in enantioselectivity is attributed to the stable adsorption of chiral modifiers on selectively exposed Pt terrace sites. The findings of this work provide a promising strategy to prepare metal nanoparticles having selectively exposed sites and offer insights into the enhancing effect of residual capping agents on the catalytic properties in structure-sensitive reactions.
- Chung, Iljun,Song, Byeongju,Kim, Jeongmyeong,Yun, Yongju
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- Efficient Asymmetric Synthesis of Ethyl (S)-4-Chloro-3-hydroxybutyrate Using Alcohol Dehydrogenase SmADH31 with High Tolerance of Substrate and Product in a Monophasic Aqueous System
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Bioreductions catalyzed by alcohol dehydrogenases (ADHs) play an important role in the synthesis of chiral alcohols. However, the synthesis of ethyl (S)-4-chloro-3-hydroxybutyrate [(S)-CHBE], an important drug intermediate, has significant challenges concerning high substrate or product inhibition toward ADHs, which complicates its production. Herein, we evaluated a novel ADH, SmADH31, obtained from the Stenotrophomonas maltophilia genome, which can tolerate extremely high concentrations (6 M) of both substrate and product. The coexpression of SmADH31 and glucose dehydrogenase from Bacillus subtilis in Escherichia coli meant that as much as 660 g L-1 (4.0 M) ethyl 4-chloroacetoacetate was completely converted into (S)-CHBE in a monophasic aqueous system with a >99.9% ee value and a high space-time yield (2664 g L-1 d-1). Molecular dynamics simulation shed light on the high activity and stereoselectivity of SmADH31. Moreover, five other optically pure chiral alcohols were synthesized at high concentrations (100-462 g L-1) as a result of the broad substrate spectrum of SmADH31. All these compounds act as important drug intermediates, demonstrating the industrial potential of SmADH31-mediated bioreductions.
- Chen, Rong,Liu, Qinghai,Wang, Hualei,Wei, Dongzhi,Xie, Youyu,Yang, Zeyu,Ye, Wenjie
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p. 1068 - 1076
(2020/07/06)
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- Molecular Insights into the Ligand-Reactant Interactions of Pt Nanoparticles Functionalized with α-Amino Acids as Asymmetric Catalysts for β-Keto Esters
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The asymmetric hydrogenation of ?-keto esters over α-amino acid-functionalized Pt nanoparticles was explored in order to expand our understanding of ligand-reactant interactions underlying the chiral induction. A comprehensive investigation aimed at the quantification of the nonlinear effects demonstrated that for most of the ligands and reactants enantiodifferentiation is determined by 1 : 1 ligand-reactant interaction. However, attachment of phenyl substituents to the ligands or reactants likely involves the formation of more intricate intermediate complexes. We have shown that the asymmetric bias is sensitive to even small changes in the geometry of the ligand. Additionally, we have found that alkali metal cations, which balance the negative charge of the ligand's carboxyl group and originate from the metal hydroxide used for ligand functionalization, play a key role in the process of chiral induction. As the nature of the cation can be varied by simply changing the metal hydroxide used during functionalization, this finding opens an additional possibility to control the stereoselectivity by tuning the ligand-reactant interaction.
- ?ulce, Anda,Mitschke, Nico,Azov, Vladimir,Kunz, Sebastian
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p. 2732 - 2742
(2019/05/15)
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- Enantioselective hydrogenation of α-ketoesters catalyzed by cinchona alkaloid stabilized Rh nanoparticles in ionic liquid
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The heterogeneous enantioselective hydrogenation of α-ketoesters catalyzed by rhodium nanoparticles (Rh NPs) in ionic liquid was studied with the stabilization and modification of cinchona alkaloids. TEM characterization showed that well-dispersed Rh NPs of about 1.96?nm were obtained in ionic liquid. The results showed that cinchona alkaloids not only had good enantiodifferentiating ability but also accelerated the catalytic reaction. Under the optimum reaction conditions, the enantiomeric excess in ethyl benzoylformate hydrogenation could reach as high as 60.9%.
- Jiang, He-yan,Xu, Jie,Sun, Bin
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p. 818 - 823
(2019/08/07)
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- One-Pot Absolute Stereochemical Identification of Alcohols via Guanidinium Sulfate Crystallization
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A novel technique for the absolute stereochemical determination of alcohols has been developed that uses crystallization of guanidinium salts of organosulfates. The simple one-pot, two-step process leverages facile formation of guandinium organosulfate single crystals for the straightforward determination of the absolute stereochemistry of enantiopure alcohols by means of X-ray crystallography. The strong hydrogen bonding network drives the stability of the crystal lattice and allows for a diverse range of organic alcohol substrates to be analyzed.
- Brummel, Beau R.,Lee, Kinsey G.,McMillen, Colin D.,Kolis, Joseph W.,Whitehead, Daniel C.
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supporting information
p. 9622 - 9627
(2019/12/02)
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- Chiron approach towards optically pure γ-valerolactone from alanine
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A concise synthesis of both enantiomers of γ-valerolactone has been developed from commercially available Alanine. The key steps in the synthesis of these γ-Lactones are DIBAL-H reduction of ester (9) followed by in situ Wittig reaction with EtO2CCH = PPh3 ylide (13) (Z/E = 1: 3.5) and one pot lactonization triggered by deprotection of O-TBS ether (14).
- Datrika, Rajender,Kallam, Srinivasa Reddy,Katta, Rambabu,Siddaiah, Vidavalur,Pratap
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supporting information
p. 2801 - 2808
(2018/12/04)
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- Hydrogenation of Ketones on Dispersed Chiral-Modified Palladium Nanoparticles
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Hydrogenation of acetophenone and esters of ketoacids with molecular hydrogen in the presence of the Pd(acac)2-cinchonidine–H2 catalytic system has been studied. The dependence of the molar ratio of (–)-cinchonidine/Pd on size and shape of palladium nanoparticles, formed in the system, also on reaction rate and enantioselectivity has been established. The nature of the regularities observed for the Pd(acac)2-cinchonidine–H2 catalytic system was discussed.
- Nindakova,Strakhov,Kolesnikov
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p. 199 - 207
(2018/03/26)
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- A thermoregulated phase-separable chiral Pt nanocatalyst for recyclable asymmetric hydrogenation of α-ketoesters
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The design and preparation of a chiral Pt nanocatalyst system possessing thermoregulated phase-separation property and its application in recyclable asymmetric hydrogenation of α-ketoesters are presented.
- Xue, Xiuru,Wang, Yanhua,Han, Fu-She
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supporting information
p. 3346 - 3349
(2017/03/22)
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- Acyclic 1,4-Stereocontrol via the Allylic Diazene Rearrangement: Development, Applications, and the Essential Role of Kinetic e Stereoselectivity in Tosylhydrazone Formation
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We report full details of a method for 1,3-reductive transposition of α-alkoxy-α,β-unsaturated hydrazones to provide E-alkenes with high 1,4-stereocontrol between the two respective allylic stereocenters. The process couples a chelation-controlled reduction of the hydrazone with an in situ allylic strain controlled retro-ene reaction of an allyl diazene, i.e., an allylic diazene rearrangement. Such stereotriads are frequently observed motifs in natural products. We observed a fortuitous kinetic preference for the E-hydrazone geometry during the hydrazonation reaction, as only the E-isomers could undergo chelation-controlled reduction.
- Shrestha, Maha L.,Qi, Wei,McIntosh, Matthias C.
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p. 8359 - 8370
(2017/08/23)
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- Esterification technique of D-methyl lactate
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The invention relates to an esterification technique of D-butyl lactate. The technique comprises the following operation steps: 1. material addition: adding methanol, D-lactic acid and a novel catalyst into a reaction kettle by using a 3.6L centrifugal pump; 2. heating: heating to 110-120 DEG C by using steam with esterification safety; 3. stirring: stirring by using a 316L self-made stirrer; 4. dropwise addition: dropwisely adding 400L/h methanol of esterification reaction by using a centrifugal pump; 5. water carrying: carrying out water carrying by using a novel water-carrying agent; and 6. carrying out esterification at the esterification temperature of 110-120 DEG C for 6 hours, thereby finishing the esterification. In general, the technique has the advantages of simple technique, low operating cost and higher extraction purity, and is convenient and quick for manufacturing.
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Paragraph 0013-0017
(2017/05/27)
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- Characterization of a novel marine microbial esterase and its use to make D-methyl lactate
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A novel marine microbial esterase PHE14 was cloned from the genome of Pseudomonas oryzihabitans HUP022 isolated from the deep sea of the western Pacific Ocean. Esterase PHE14 exhibited very good tolerance to most organic solvents, surfactants and metal ions tested, thus making it a good esterase candidate for organic synthesis that requires an organic solvent, surfactants or metal ions. Esterase PHE14 was utilized as a biocatalyst in the asymmetric synthesis of D-methyl lactate by enzymatic kinetic resolution. D-methyl lactate is a key chiral chemical. Contrary to some previous reports, the addition of an organic solvent and surfactants in the enzymatic reaction did not have a beneficial effect on the kinetic resolution catalyzed by esterase PHE14. Our study is the first report on the preparation of the enantiomerically enriched product D-methyl lactate by enzymatic kinetic resolution. The desired enantiomerically enriched product D-methyl lactate was obtained with a high enantiomeric excess of 99% and yield of 88.7% after process optimization. The deep sea microbial esterase PHE14 is a green biocatalyst with very good potential in asymmetric synthesis in industry and can replace the traditional organic synthesis that causes pollution to the environment.
- Wang, Yilong,Zhang, Yun,Sun, Aijun,Hu, Yunfeng
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p. 1396 - 1402
(2016/09/07)
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- On-Column Reaction Set-Up for High-Throughput Screenings and Mechanistic Investigations
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A screening platform, which offers a high-throughput approach as well as an easy investigation of kinetic isotope effects, applicable to a wide range of reactions is presented. To illustrate the high potential of this approach, the asymmetric transfer hydrogenation of methyl benzoylformate with copper(II) bis(oxazoline) and Hantzsch ester was examined. Accordingly, the enantioselectivities of the reaction performed on-column in a microcapillary were comparable to standard reaction conditions, however, we were able achieve catalysis and analysis in a single step in less than 30 min. The throughput can be increased by simultaneous investigation of different substrates without increasing the overall analysis time. Use of di-deuterated Hantzsch ester allowed us to investigate the kinetic isotope effect of the transfer hydrogenation reaction only requiring a minute amount of the deuterated transfer hydrogenation reagent. Hence we were able to get further insights into the mechanism of the asymmetric transfer hydrogenation using Hantzsch ester as hydrogen source. The here presented technique is broadly applicable to study isotope effects on a very small scale, which is a rapid and an inexpensive alternative compared to conventional experiments.
- Stockinger, Skrollan,Troendlin, Johannes,Rominger, Frank,Trapp, Oliver
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p. 3513 - 3520
(2016/01/25)
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- Macrocyclic inhibitors of flaviviridae viruses
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Provided are compounds of Formula I: and pharmaceutically acceptable salts and esters thereof. The compounds, compositions, and methods provided are useful for the treatment of virus infections, particularly hepatitis C infections.
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Page/Page column
(2015/08/03)
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- Integration of rigid and flexible organic parts for the construction of a homochiral metal-organic framework with high porosity
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Presented is a pair of homochiral metal-organic frameworks built from mixed ligands integrating rigid and flexible organic parts, and each compound shows high porosity and can be used for enantioselective separation of racemic 1-phenethylalcohol and methyl lactate. This journal is
- Xu, Zhong-Xuan,Tan, Yan-Xi,Fu, Hong-Ru,Kang, Yao,Zhang, Jian
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supporting information
p. 2565 - 2568
(2015/03/05)
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- Size-Dependent Enantioselective Adsorption of Racemic Molecules through Homochiral Metal-Organic Frameworks Embedding Helicity
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Homochiral metal-organic frameworks (HMOFs) are efficient materials for enantioselective adsorption. However, the combination of size selectivity and enantioselectivity is still a major challenge in the field of HMOFs. Herein, two enantiomorphic HMOFs built from predesigned proline-derived ligands are presented. Both of them show multiple homochiral features: they contain four different helical chains and three types of helical channels. Due to the size effect of the helical channels, each HMOF can enantioselectively adsorb methyl lactate with high ee. The results reveal a new approach toward size-dependent enantioselective separation of racemic compounds by using HMOFs built from inexpensive proline derivatives.
- Xu, Zhong-Xuan,Fu, Hong-Ru,Wu, Xin,Kang, Yao,Zhang, Jian
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p. 10236 - 10240
(2015/07/07)
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- Altering the substrate specificity of reductase CgKR1 from Candida glabrata by protein engineering for bioreduction of aromatic α-keto esters
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A versatile keto ester reductase CgKR1, exhibiting a broad substrate spectrum, was obtained from Candida glabrata by genome data mining. It showed the highest activity toward an aliphatic β-keto ester, ethyl 4-chloro-3-oxobutanoate (COBE), but much lower activity toward bulkier α-keto esters with an aromatic group, such as methyl ortho- chlorobenzoylformate (CBFM) and ethyl 2-oxo-4-phenylbutyrate (OPBE). By rational design of the active pocket, the substrate specificity of the reductase was significantly altered and this tailor-made reductase showed a much higher activity toward aromatic α-keto esters (~7-fold increase in k cat/Km toward CBFM) and lower activity toward aliphatic keto esters (~12-fold decrease in kcat/Km toward COBE). Meanwhile, the thermostability of the reductase was enhanced by a consensus approach. Such improvements may yield practical catalysts for the asymmetric bioreduction of these aromatic α-keto esters
- Huang, Lei,Ma, Hong-Min,Yu, Hui-Lei,Xu, Jian-He
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p. 1943 - 1948
(2014/07/07)
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- Solid-phase synthesis of tetrahydropyridazinedione-constrained peptides
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The design and solid-phase synthesis of tetrahydropyridazine-3,6-dione (Tpd) peptidomimetics derived from backbone-aminated peptides is reported. The described protocol features the synthesis of chiral α-hydrazino acids suitable for chemoselective incorporation into growing peptide chains. Acid-catalyzed cyclization to form the Tpd ring during cleavage affords the target peptidomimetics in good yield and purity. The scope of Tpd incorporation is demonstrated through the synthesis of constrained peptides featuring nucleophilic/electrophilic side chains and sterically encumbered α-substituted hydrazino acid residues. (Chemical Equation Presented).
- Kang, Chang Won,Ranatunga, Sujeewa,Sarnowski, Matthew P.,Del Valle, Juan R.
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supporting information
p. 5434 - 5437
(2015/02/19)
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- Bare histidine-serine models: Implication and impact of hydrogen bonding on nucleophilicity
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A new family of 2-hydroxyalk(en/yn)ylimidazoles has been evaluated as serine-histidine bare dyad models for the ring-opening reaction of L-lacOCA, a cyclic O-carboxyanhydride. These models were selected to unravel the implication of intramolecular hydrogen bonding and to substantiate its influence on the nucleophilicity of the alcohol moiety, as it is suspected to occur in enzyme active sites. Although designed to exclusively facilitate the preliminary step of proton transfer during the studied ring-opening reaction, these minimalistic models depicted a measureable increase in reactivity relative to the isolated fragments. A couple of reliable experimental and theoretical methods have been developed to readily monitor the strength of the intramolecular hydrogen bond in dilute solution. Results show that the folded conformers are the most nucleophilic species because of the intramolecular hydrogen bond. Copyright
- Leclaire, Julien,Mazari, Messaoud,Zhang, Yuan,Bonduelle, Colin,Thillaye Du Boullay, Olivier,Martin-Vaca, Blanca,Bourissou, Didier,De Riggi, Innocenzo,Fortrie, Rémy,Fotiadu, Frédéric,Buono, Gérard
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supporting information
p. 11301 - 11309
(2013/09/02)
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- Bridging racemic lactate esters with stereoselective polylactic acid using commercial lipase catalysis
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A productive and enantioselective hydrolysis of racemic mixtures of lactate esters with commercial Candida rugosa lipase was performed. This step contributes to a novel envisioned route for stereoselective PLA production by combining recent chemocatalytic developments with this biocatalytic contribution, foreseeing two separate l- and d-lactate enantiomer streams. A study of the hydrolysis kinetics identified an unexpected rate determining step at the origin of an unprecedented ester reactivity order.
- Van Wouwe, Pieter,Dusselier, Michiel,Basic, Aurelie,Sels, Bert F.
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supporting information
p. 2817 - 2824
(2013/10/08)
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- Cyclodextrin-based ionic liquids as enantioselective stationary phases in gas chromatography
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New permethylated mono-6-deoxy-6-pyridin-1-ium and mono-6-deoxy-6-(1-vinyl- 1H-imidazol-3-ium)-α- and -β-cyclodextrin trifluoromethanesulfonate ionic liquids were synthesized from the corresponding permethylated mono-6-hydroxycyclodextrins in a one-pot reaction and solvent-free procedure. Regioselective transformation of native α- and β-cyclodextrins with the use of a bulky tert-butyldiphenylsilyl protecting group afforded the desired 6-monosubstituted permethylated cyclodextrin derivatives in moderate yields. The new ionic liquids were tested as stationary phases in capillary GC columns towards chiral discrimination in enantio-GC analysis of racemic mixtures. The permethylated 6-deoxy-6-pyridin-1-ium-α-cyclodextrin trifluoromethanesulfonate displayed good enantiomeric separations for some racemic esters and lactones, as well as epoxides. In particular, for both the racemic whiskey lactone and the high boiling point menthyl laurate, not successfully separated in a commercial cyclodextrin phase, the enantiomeric separations were achieved isothermally at 140 °C. In phase: Permethylated mono-6-hydroxy-α- and -β-cyclodextrins react with pyridine or 1-vinylimidazole in the presence of triflic anhydride in a solvent-free procedure to yield new roomerature ionic liquids (ILs). These ILs have been used as stationary phases in gas chromatography; enantiomeric separations are achieved (see figure for whiskey lactone) with permethylated mono-6-deoxy-6-(pyridin-1-ium)-α-cyclodextrin trifluoromethanesulfonate. Copyright
- Costa, Nuno,Matos, Sara,Da Silva, Marco D. R. Gomes,Pereira, M. Manuela A.
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p. 1466 - 1474
(2014/01/06)
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- Total syntheses of the gregatins A-D and aspertetronin A: Structure revisions of these compounds and of aspertetronin B, together with plausible structure revisions of gregatin E, cyclogregatin, graminin A, the penicilliols A and B, and the huaspenones A and B
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Comprehensive comparisons of 1H and 13C NMR chemical shift values in the furanone cores a, b, and c provide plausible support for a reassessment of the furanone nuclei of the title compounds from b to c. Total syntheses via enantiomerically pure lactic esters were based on the Seebach-Frater "self-reproduction of stereocenters" methodology. Attachment of the hexadienyl side-chain in a trans,trans-selective manner was achieved by addition of the Seebach-Frater enolate to trans-hex-4-en-1-al rather than to trans-hex-3-en-1-al. The type-c furanone cores of the synthetic materials were reached by single or double acylation of a model γ-hydroxy-β-oxo ester (compound 50) and its hexadiene-containing counterpart 29. Our syntheses confirmed the novel connectivities in six compounds. In addition, they required revision of the configuration of a quaternary carbon atom in five cases. Moreover, they allowed elucidation of the configurations of four previously unassigned stereocenters. Hindsight analyses of why the furanone cores of the title compounds had been misinterpreted as a and/or b instead of c are given. Why the stereocenters in the heterocycles had been incorrectly configured, on the bases (a) of relay studies in the 1960s, and (b) of a 1984 total synthesis of gregatin B, is also discussed.
- Burghart-Stoll, Heike,Brueckner, Reinhard
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supporting information; experimental part
p. 3978 - 4017
(2012/10/18)
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- Enhancement of the performance of a platinum nanocatalyst confined within carbon nanotubes for asymmetric hydrogenation
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Going through the proper channels: A highly active and enantioselective heterogeneous asymmetric catalyst was fabricated by confining Pt nanoparticles that are modified with cinchonidine within the channels of carbon nanotubes. A high turnover frequency (TOF) and enantioselectivity are achieved when using this catalyst for the asymmetric hydrogenation of α-ketoesters. Copyright
- Chen, Zhijian,Guan, Zaihong,Li, Mingrun,Yang, Qihua,Li, Can
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supporting information; experimental part
p. 4913 - 4917
(2011/06/23)
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- Novel anti-Prelog stereospecific carbonyl reductases from Candida parapsilosis for asymmetric reduction of prochiral ketones
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The application of biocatalysis to the synthesis of chiral molecules is one of the greenest technologies for the replacement of chemical routes due to its environmentally benign reaction conditions and unparalleled chemo-, regio- and stereoselectivities. We have been interested in searching for carbonyl reductase enzymes and assessing their substrate specificity and stereoselectivity. We now report a gene cluster identified in Candida parapsilosis that consists of four open reading frames including three putative stereospecific carbonyl reductases (scr1, scr2, and scr3) and an alcohol dehydrogenase (cpadh). These newly identified three stereospecific carbonyl reductases (SCRs) showed high catalytic activities for producing (S)-1-phenyl-1,2-ethanediol from 2-hydroxyacetophenone with NADPH as the coenzyme. Together with CPADH, all four enzymes from this cluster are carbonyl reductases with novel anti-Prelog stereoselectivity. SCR1 and SCR3 exhibited distinct specificities to acetophenone derivatives and chloro-substituted 2-hydroxyacetophenones, and especially very high activities towards ethyl 4-chloro-3-oxobutyrate, a β-ketoester with important pharmaceutical potential. Our study also showed that genomic mining is a powerful tool for the discovery of new enzymes.
- Nie, Yao,Xiao, Rong,Xu, Yan,Montelione, Gaetano T.
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experimental part
p. 4070 - 4078
(2011/07/08)
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- Organosoluble zirconium phosphonate nanocomposites and their supported chiral ruthenium catalysts: The first example of homogenization of inorganic-supported catalyst in asymmetric hydrogenation
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In this article, we report the synthesis, structure, morphologies, and asymmetric catalytic properties of a series of novel organosoluble zirconium phosphonate nanocomposites and their supported chiral ruthenium catalysts, which have a good organosolubility (0.1-0.5 g mL-1) in various solvents and mesoporous, filiform, and layered structures. Due to the organosoluble properties in various organic solvents, the first homogenization of zirconium phosphonate-supported catalyst was realized in the field of catalysis. In the asymmetric hydrogenation of substituted α-ketoesters, enantioselectivities (74.3-84.7% ee) and isolated yields (86.7-93.6%) were higher than the corresponding homogeneous Ru(p-cymene)(S-BINAP)Cl2 due to the confinement effect caused by the remaining mesopores in the backbone of the zirconium phosphonate. After completing the reaction, the supported catalyst can be readily recovered in quantitative yield by adding cyclohexane and centrifugation, and reused for five consecutive runs without significant loss in catalytic activity.
- Chen, Taotao,Ma, Xuebing,Wang, Xiaojia,Wang, Qiang,Zhou, Jinqin,Tang, Qian
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experimental part
p. 3325 - 3335
(2011/05/13)
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- METHOD FOR PRODUCING OPTICALLY ACTIVE 2-HYDROXY ESTER AND NOVEL INTERMEDIATE COMPOUND
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Disclosed is a method for producing an optically active 2-hydroxy ester, comprising selectively esterifying one enantiomer of a racemic 2-hydroxy ester in a solvent containing a catalyst such as tetramisole or benzotetramisole, and a carboxylic acid anhydride, or a carboxylic acid anhydride and a carboxylic acid. In particular, in the case where the solvent contains a carboxylic acid anhydride, but does not contain a carboxylic acid, as the carboxylic acid anhydride, a carboxylic acid anhydride containing a tertiary or quaternary carbon atom in the a-position is used. On the other hand, in the case where the solvent contains a carboxylic acid anhydride and a carboxylic acid, as the carboxylic acid, a carboxylic acid containing a tertiary or quaternary carbon atom in the a-position is used.
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Page/Page column 11
(2012/01/13)
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- Kinetic resolution of the racemic 2-hydroxyalkanoates using the enantioselective mixed-anhydride method with pivalic anhydride and a chiral acyl-transfer catalyst
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A variety of optically active 2-hydroxyalkanoates and the corresponding 2-acyloxyalkanoates are produced by the kinetic resolution of racemic 2-hydroxyalkanoates by using achiral 2,2-diarylacetic acid with hindered carboxylic anhydrides as the coupling reagents. The combined use of diphenylacetic acid, pivalic anhydride, and (+)-(R)-benzotetramisole ((R)-BTM) effectively produces (S)-2-hydroxyalkanoates and (R)-2-acyloxyalkanoates from the racemic 2-hydroxyalkanoates (s-values = 47-202). This protocol directly provides the desired chiral 2-hydroxyalkanoate derivatives from achiral diarylacetic acid and racemic secondary alcohols that do not include the sec-phenethyl alcohol moiety by using the transacylation process to generate the mixed anhydrides from the acid components with bulky carboxylic anhydrides under the influence of the chiral acyl-transfer catalyst. The transition state that provides the desired (R)-2-acyloxyalkanoate from (R)-2-hydroxyalkanoate included in the racemic mixture is disclosed by DFT calculations, and the structural features of the transition form are also discussed.
- Shiina, Isamu,Nakata, Kenya,Ono, Keisuke,Sugimoto, Masuhiro,Sekiguchi, Akihiro
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supporting information; experimental part
p. 167 - 172
(2010/03/26)
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- Sulfonate Catalyst and Method of Producing Alcohol Compound Using the Same
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A sulfonate catalyst represented by the formula below and a ketone compound are placed in a solvent, and the ketone compound is hydrogenated by mixing in the presence of hydrogen to produce an optically active alcohol.
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Page/Page column 10
(2008/12/07)
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- A surprising mechanistic "switch" in Lewis acid activation: A bifunctional, asymmetric approach to α-hydroxy acid derivatives
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We report a detailed synthetic and mechanistic study of an unusual bifunctional, sequential hetero-Diels-Alder/ring-opening reaction in which chiral, metal complexed ketene enolates react with o-quinones to afford highly enantioenriched, α-hydroxylated carbonyl derivatives in excellent yield. A number of Lewis acids were screened in tandem with cinchona alkaloid derivatives; surprisingly, trans-(Ph3P)2PdCl2 was found to afford the most dramatic increase in yield and rate of reaction. A series of Lewis acid binding motifs were explored through molecular modeling, as well as IR, UV, and NMR spectroscopy. Our observations document a fundamental mechanistic "switch", namely the formation of a tandem Lewis base/Lewis acid activated metal enolate in preference to a metal-coordinated quinone species (as observed in other reactions of o-quinone derivatives). This new method was applied to the syntheses of several pharmaceutical targets, each of which was obtained in high yield and enantioselectivity.
- Abraham, Ciby J.,Paull, Daniel H.,Bekele, Tefsit,Scerba, Michael T.,Dudding, Travis,Lectka, Thomas
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supporting information; experimental part
p. 17085 - 17094
(2009/04/13)
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- Catalytic asymmetric hydrogenation of α-ketoesters and quinoline using electronically enriched BINAP
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Electronically enriched chiral BINAP derivatives were synthesized incorporating electron-donating substituents at the para-phenyl position and evaluated for the Ru-catalyzed homogeneous asymmetric hydrogenation of α-ketoesters with up to 92% ee. These diphophosphines were also excellent ligands for the iridium-catalyzed asymmetric hydrogenation of quinolines.
- Jahjah, Mohamad,Alame, Mohamad,Pellet-Rostaing, Stephane,Lemaire, Marc
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p. 2305 - 2312
(2008/03/12)
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- A new class of versatile chiral-bridged atropisomeric diphosphine ligands: Remarkably efficient ligand syntheses and their applications in highly enantioselective hydrogenation reactions
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A series of chiral diphosphine ligands denoted as PQ-Phos was prepared by atropdiastereoselective Ullmann coupling and ring-closure reactions. The Ullmann coupling reaction of the biaryl diphosphine dioxides is featured by highly efficient central-to-axial chirality transfer with diastereomeric excess >99%. This substrate-directed diastereomeric biaryl coupling reaction is unprecedented for the preparation of chiral diphosphine dioxides, and our method precludes the tedious resolution procedures usually required for preparing enantiomerically pure diphosphine ligands. The effect of chiral recognition was also revealed in a relevant asymmetric ring-closure reaction. The chiral tether bridging the two aryl units creates a conformationally rigid scaffold essential for enantiofacial differentiation; fine-tuning of the ligand scaffold (e.g., dihedral angles) can be achieved by varying the chain length of the chiral tether. The enantiomerically pure Ru- and Ir-PQ-Phos complexes have been prepared and applied to the catalytic enantioselective hydrogenations of α- and β-ketoesters (C=O bond reduction), 2-(6′-methoxy- 2′-naphthyl)-propenoic acid, alkyl-substituted β-dehydroamino acids (C=C bond reduction), and N-heteroaromatic compounds (C=N bond reduction). An excellent level of enantioselection (up to 99.9% ee) has been attained for the catalytic reactions. In addition, the significant ligand dihedral angle effects on the Ir-catalyzed asymmetric hydrogenation of N-heteroaromatic compounds were also revealed.
- Qiu, Liqin,Kwong, Fuk Yee,Wu, Jing,Lam, Wai Har,Chan, Shusun,Yu, Wing-Yiu,Li, Yue-Ming,Guo, Rongwei,Zhou, Zhongyuan,Chan, Albert S. C.
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p. 5955 - 5965
(2007/10/03)
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- Highly enantioselective hydrogenation of α-keto esters catalyzed by Ru-tunephos complexes
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Various enantiomerically pure α-hydroxy esters were synthesized by asymmetric hydrogenation of α-keto esters catalyzed by Ru-C n-Tunephos complex. Up to 97.1% ee has been achieved for both α-aryl and α-alkyl substituted α-keto esters. Georg Thieme Verlag Stuttgart.
- Wang, Chun-Jiang,Sun, Xianfeng,Zhang, Xumu
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p. 1169 - 1172
(2007/10/03)
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- Preparation of aminophosphines
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Disclosed is a process for the preparation of phosphine-aminophosphines that are useful in the formation of catalysts useful in carrying out a wide variety of reactions such as asymmetric hydrogenations, asymmetric reductions, asymmetric hydroborations, asymmetric olefin isomerizations, asymmetric hydrosilations, asymmetric allylations, asymmetric conjugate additions, and asymmetric organometallic additions. The process comprises the steps of (1) contacting a compound of formula 2 [in-line-formulae]R2P—L—NHR3??2[/in-line-formulae] with phosphorus trihalide PX3 in the presence of an inert, organic solvent and an acid acceptor to produce intermediate compound having formula 3 (2) contacting intermediate compound 3 with a reactant having the formula R1—M1, R2—M1 or a mixture thereof.
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Page/Page column 15
(2010/02/11)
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- Synthesis and application of phosphinoferrocenylaminophosphine ligands for asymmetric catalysis
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(Chemical Equation Presented) A new class of bidentate ligands utilizing a phosphine-aminophosphine structure has been prepared on a ferrocenylethyl backbone in a straightforward and scalable fashion from acetylferrocene. The unique property of the α-ferrocenyl carbonium ion that allows the replacement of a variety of "leaving groups" with retention of configuration greatly facilitates the synthesis, and a number of ligands have been prepared by varying the nitrogen and phosphorus substituents on the aminophosphine. These readily prepared phosphinoferrocenylaminophosphines, known as BoPhoz ligands, show surprising hydrolytic and air stability, with no degradation after 3 years open to the air. The rhodium complexes of these ligands show exceedingly high enantioselectivities (generally > 95% ee) and activities often in excess of 50 000 catalyst turnovers per hour for the asymmetric hydrogenation of a wide variety of dehydro-α-amino acid and itaconic acid derivatives. They also show high activity and good to excellent enantioselectivity for the hydrogenation of a number of α-ketoesters.
- Boaz, Neil W.,Mackenzie, Elaine B.,Debenham, Sheryl D.,Large, Shannon E.,Ponasik Jr., James A.
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p. 1872 - 1880
(2007/10/03)
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- Ruthenium catalyzed asymmetric hydrogenation of α- and β-keto esters in ionic liquids using chiral P-Phos ligand
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Chiral dipyridylphosphine ligand P-Phos was used in the Ru catalyzed asymmetric hydrogenation of α- and β-keto esters in room temperature ionic liquids (RTILs) with high conversions and good to excellent enantioselectivities. The catalyst was recycled by simple extraction and reused five times without loss of activity and enantioselectivity.
- Lam, Kim Hung,Xu, Lijin,Feng, Lichun,Ruan, Jiwu,Fan, Qinghua,Chan, Albert S.C.
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p. 903 - 908
(2007/10/03)
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- PROCESS FOR PRODUCING OPTICALLY ACTIVE ALCOHOL IN THE PRESENCE OF RHODIUM, A CHIRAL FERROCENYLDIPHOSPHINE AND AN OPTICALLY ACTIVE DIAMINE
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A novel process for producing optically active alcohols through asymmetric hydrogenation of prochiral carbonyl compounds allows high-yield, industrially favorable production of an optically active alcohol at a high enantiomeric excess. The process is charaterized in that the asymmetric hydrogenation is carried out in the absence of a base and in the presence of a rhodium complex or a salt thereof; an optically active ferrocenyl diphosphine; and an optically active diamine.
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- Vitamin D analogues
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Vitamin D compounds formula I wherein R represents hydrogen, or R represents (C1-C6)alkyl, phenyl, or (C7-C9)aralkyl, optionally substituted with one or more groups selected from (C1-C3)alkyl, F, phenyl; n is an integer having the value 0, 1, or 2; and X represents hydroxy or halogen.
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- Observation of high enantioselectivity for the gas phase hydrogenation of methyl pyruvate using supported Pt catalysts pre-modified with cinchonidine
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Pt supported on α-Al2O3, γ-Al2O3 and SiO2 pre-modified with cinchonidine gives over 50% ee in the hydrogenation of methyl pyruvate to methyl lactate using gas phase reactants at 40°C giving the first clear observation of high enantioselection at the gas/solid interface.
- Von Arx, Matthias,Dummer, Nicholas,Willock, David J.,Taylor, Stuart H.,Wells, Richard P. K.,Wells, Peter B.,Hutchings, Graham J.
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p. 1926 - 1927
(2007/10/03)
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- Phosphinoferrocenylaminophosphines as novel and practical ligands for asymmetric catalysis
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(Matrix Presented) A new series of ligands with a novel phosphine-aminophosphine ligation design as depicted in structure 1 has been prepared on a ferrocenylethyl backbone. These BoPhoz ligands of structure 2 have afforded exceedingly high activity and enantioselectivity in the rhodium-catalyzed asymmetric hydrogenation of dehydro-α-amino acid derivatives, itaconic acids, and α-ketoesters. These air-stable ligands are readily prepared from cost-effective and non-pyrophoric intermediates.
- Boaz, Neil W.,Debenham, Sheryl D.,Mackenzie, Elaine B.,Large, Shannon E.
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p. 2421 - 2424
(2007/10/03)
-
- Enantiomeric inclusion of α-hydroxy esters by (R)-(1-naphthyl)glycyl- (R)-phenylglycine and the crystal structures of the inclusion cavities
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A simple dipeptide, (R)-(1-naphthyl)glycyl-(R)-phenylglycine [(R,R)-1], formed inclusion compounds with several α-hydroxy esters (2) with high enantioselectivity. By crystallization of a mixture of the dipeptide [(R,R)- 1] and racemic 2a [MeCH(OH)COOMe] from methanol, asymmetric recognition occurred to give an inclusion compound that contains the S form of 2a in 89% ee. X-ray crystallographic study of the inclusion compound elucidated that the dipeptide molecules arrange in a 'folded antiparallel' β-sheetlike structure to accommodate the α-hydroxy ester in the pocket-type cavity surrounded by naphthyl and phenyl groups on the sheet. Similarly, 2b [MeCH(OH)-COOEt] and 2f [dihydro-3-hydroxy-4,4-dimethyl-2(3H)-furanone] were included with high enantioselectivity of the S form. When bulkier 21 [t- BuCH(OH)COOMe] was used as a guest molecule, the arrangement of dipeptide molecules changed to an 'extended antiparallel' mode, where the naphthyl and phenyl groups arranged in a 'parallel stacked and displaced' mode and a channel-type cavity was constructed. The guest molecules were accommodated via hydrogen bonding in the channel-type cavity with high enantioselectivity of the S form (82% ee). In the case of 2k [i-PrCH-(OH)COOMe], optically pure (S)-2k formed the dipeptide sheet with the 'folded antiparallel' structure by cocrystallization with (R,R)-1, while the 'extended antiparallel' structure appeared in the inclusion of racemic 2k.
- Akazome,Takahashi,Ogura
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p. 2293 - 2300
(2007/10/03)
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- Enantioselective hydrogenation of pyruvates over polymer-stabilized and supported platinum nanoclusters
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The cinchonidine-modified enantioselective hydrogenation of pyruvates has been studied over polyvinylpyrrolidone-stabilized platinum (PVP-Pt) and the corresponding alumina-supported platinum (Al2O3-Pt) clusters. It is shown that the catalysts with particle size less than 2.0 nm demonstrate >90% enantioselectivity in favor of (R)-lactates. The solvent effect is similar to that over the conventional supported platinum catalyst except for tetrahydrofuran. These colloidal and supported clusters are stable with no obvious loss of activity and enantioselectivity even after 18 months standing in air at room temperature. Molecular mechanics calculations of the modifier- reactant interaction on the platinum surface suggest that it is possible to obtain good enantioselectivity on the small clusters.
- Zuo, Xiaobin,Liu, Hanfan,Guo, Dawei,Yang, Xiaozhen
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p. 7787 - 7804
(2007/10/03)
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- Baker's Yeast-Mediated Reductions of α-Keto Esters and an α-Keto-β-Lactam. Two Routes to the Paclitaxel Side Chain
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Baker's yeast (Saccharomyces cerevisiae) has been used to reduce a series of alkyl esters derived from pyruvate and benzoylformate. Both the yield and enantioselectivities of these reductions were maximized when methyl esters were used, and the (R)-alcohols were isolated in all instances. Yeast-mediated ester hydrolysis was a significant side reaction for products derived from long-chain alcohols. In the case of ethyl benzoylformate, the addition of methyl vinyl ketone increased the enantioselectivity of the reduction. These reductions were applied to two syntheses of the paclitaxel C13 side chain [(2R,3S)-N-benzoyl-3-phenylisoserine]. In the first, a racemic α-keto-β-azido ester was reduced by whole cells of Baker's yeast to afford a diastereomeric mixture in which the desired product predominated and could be isolated chromatographically. In the second, an easily synthesized α-keto-β-lactam was reduced by yeast cells to afford the desired eis isomer as well as the undesired trans diastereomer. Substituting a yeast strain deficient in fatty acid synthase in this reduction suppressed formation of the trans diastereomer. These results suggest that a single enzyme is responsible for both the D- and L-cis-alcohols resulting from reduction of the α-keto-β-lactam. All of the yeast strains used in this project are available commercially, and these biocatalytic reductions require only common laboratory equipment.
- Kayser, Margaret M.,Mihovilovic, Marko D.,Kearns, Jeff,Feicht, Anton,Stewart, Jon D.
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p. 6603 - 6608
(2007/10/03)
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- Asymmetric reactions of α-ketoacid-derived hemiacetals: Stereoselective synthesis of α-hydroxy acids
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N-Acylation of prolinol with α-ketoacid chlorides results in concomitant hemiacetalization of the α-keto amide by the prolinol hydroxyl group. (R) or (S) α-hydroxy acids are obtained with good enantiomeric excess by stereodivergent reduction of these hemiacetals. Reaction with Grignard reagents at ambient temperature furnishes (R) α-alkyl mandelic acids with good stereoselectivity.
- Pansare, Sunil V.,Ravi, R. Gnana
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p. 14549 - 14564
(2007/10/03)
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