- Mixtures of chiral monodentate phosphites, phosphonites and phosphines as ligands in Rh-catalyzed hydrogenation of N-acyl enamines: Extension of the combinatorial approach
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Mixtures of BINOL-derived monodentate phosphites and phosphonites have been reacted with Rh-salts to form three (pre)catalysts, which are in equilibrium; two homo-combinations MLaLa and MLbL b as well as the het
- Reetz, Manfred T.,Mehler, Gerlinde,Meiswinkel, Andreas
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- Efficient dynamic kinetic resolution of secondary amines with Pd on alkaline earth salts and a lipase
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Combination of Pd, supported on alkaline earth type supports with a lipase results in a selective catalytic system for dynamic kinetic resolution of benzylic amines. The Royal Society of Chemistry 2005.
- Parvulescu, Andrei,De Vos, Dirk,Jacobs, Pierre
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- Platinum-encapsulated zeolitically microcapsular catalyst for one-pot dynamic kinetic resolution of phenylethylamine
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The platinum-encapsulated zeolitically microcapsular catalyst, associated with the immobilized Candida antartica lipase B (Novozyme435), is successfully employed in the dynamic kinetic resolution of phenylethylamine. A conversion of 80% and a selectivity of 95% are achieved, and negligible loss of activity is detected even after reaction of 5 runs. It is found that the existence of the silicalite-1 shell not only effectively prevents the deactivation of both enzyme and Pt by isolating them in different regions of reaction system, but also significantly reduces the formation of by-products on the Pt nanoparticles within the protected space of zeolitic microcapsule. Such features of zeolitic shell should further promote the designing of various catalysts for multistep reaction network.
- Shi, Jing,Li, Xiang,Wang, Quanrui,Zhang, Yahong,Tang, Yi
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- ASYMMETRIC SYNTHESIS OF N-ACETYL-PHENYLETHYLAMINE
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The chromium tricarbonyl complex of the benzaldehyde acetale derived from R,R-butane-2,3-diol undergoes completely stereoselective displacement, with retention of configuration, of the pro-R acetal oxygen on treatment with titanium tetrachloride and trimethyl aluminum: A subsequent Ritter reaction releases the RR-butane-2,3-diol intact and generates stereospeciphically after decomplexation R-N-acetyl-phenylethylamine.
- Davies, Stephen G.,Newton, Roger F.,Williams, Jonathan M.J.
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- Challenging the major/minor concept in Rh-catalyzed asymmetric hydrogenation
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Herein, we provide evidence showing that the long-held major-minor concept for catalytic asymmetric reactions needs to be readdressed. The asymmetric hydrogenation of enamide 1 catalyzed by the chiral Rh(I) complex of (R,R)-BenzP quantitatively yields the
- Gridnev, Ilya D.,Imamoto, Tsuneo
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- Homochiral Porous Framework as a Platform for Durability Enhancement of Molecular Catalysts
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Self-quenching and vulnerability of active sites are major issues posed for practical applications of highly efficient chiral organometallic catalysts. Here, we demonstrate an effective strategy to address these challenges by constructing them into homoch
- Sun, Qi,Dai, Zhifeng,Meng, Xiangju,Xiao, Feng-Shou
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- Biocatalytic, Intermolecular C?H Bond Functionalization for the Synthesis of Enantioenriched Amides
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Directed evolution of heme proteins has opened access to new-to-nature enzymatic activity that can be harnessed to tackle synthetic challenges. Among these, reactions resulting from active site iron-nitrenoid intermediates present a powerful strategy to forge C?N bonds with high site- and stereoselectivity. Here we report a biocatalytic, intermolecular benzylic C?H amidation reaction operating at mild and scalable conditions. With hydroxamate esters as nitrene precursors, feedstock aromatic compounds can be converted to chiral amides with excellent enantioselectivity (up to >99 % ee) and high yields (up to 87 %). Kinetic and computational analysis of the enzymatic reaction reveals rate-determining nitrenoid formation followed by stepwise hydrogen atom transfer-mediated C?H functionalization.
- Arnold, Frances H.,Athavale, Soumitra V.,Gao, Shilong,Hirschi, Jennifer S.,Liu, Zhen,Mallojjala, Sharath Chandra
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supporting information
p. 24864 - 24869
(2021/10/15)
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- Metal coordination compound, intermediate, preparation method and applications thereof
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The invention discloses a metal coordination compound, an intermediate, a preparation method and applications thereof. According to the invention, the metal coordination compound represented by a formula I can be used as a catalyst for an asymmetric catalytic hydrogenation reaction to efficiently and catalytically synthesize a series of chiral beta-aryl amides with high optical purity (ee value ofmore than 99%) particularly to asymmetrically and catalytically hydrogenate a tetra-substituted alkenyl amide compound to synthesize a chiral amide with high optical purity (ee value of more than 60%), wherein the ligand bearing capacity (s/c) can reach 100000.
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Paragraph 0398-0403
(2020/05/01)
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- Diaza-Crown Ether-Bridged Chiral Diphosphoramidite Ligands: Synthesis and Applications in Asymmetric Catalysis
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A small library of diaza-crown ether-bridged chiral diphosphoramidite ligands was prepared. In the rhodium-catalyzed asymmetric hydrogenation and hydroformylation reactions, these ligands exhibited distinct properties in catalytic activity and/or enantioselectivity. Hydrogenated products with opposite absolute configurations could be obtained in high yields with excellent ee values by utilizing (S,S)-L1 and (S,S)-L3, respectively. Meanwhile, the addition of alkali metal cations caused variations in catalytic outcomes, showing the supramolecular tunability of these Rh/diphosphoramidite catalytic systems.
- Luo, Yier,Ouyang, Guanghui,Tang, Yuping,He, Yan-Mei,Fan, Qing-Hua
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p. 8176 - 8184
(2020/07/15)
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- Development of robust heterogeneous chiral rhodium catalysts utilizing acid?base and electrostatic interactions for efficient continuous-flow asymmetric hydrogenations
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Heterogeneous chiral Rh catalysts based on acid?base and electrostatic interactions have been developed. The robust catalysts demonstrate high activity and selectivity in the continuous-flow asymmetric hydrogenation of a wide variety of enamides and dehyd
- Saito, Yuki,Kobayashi, Shu
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supporting information
p. 16546 - 16551
(2020/11/09)
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- N-acetylation of amines in continuous-flow with acetonitrile—no need for hazardous and toxic carboxylic acid derivatives
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A continuous-flow acetylation reaction was developed, applying cheap and safe reagent, acetonitrile as acetylation agent and alumina as catalyst. The method developed utilizes milder reagent than those used conventionally. The reaction was tested on various aromatic and aliphatic amines with good conversion. The catalyst showed excellent reusability and a scale-up was also carried out. Furthermore, a drug substance (paracetamol) was also synthesized with good conversion and yield.
- Fül?p, Ferenc,Mándity, István M.,Orsy, Gy?rgy
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- A Bulky Three-Hindered Quadrant Bisphosphine Ligand: Synthesis and Application in Rhodium-Catalyzed Asymmetric Hydrogenation of Functionalized Alkenes
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A bulky three-hindered quadrant bisphosphine ligand, di-1-adamantylphosphino(tert-butylmethylphosphino)methane, named BulkyP*, has been synthesized via a convergent short pathway with chromatography-free procedures. The ligand is a crystalline solid and can be readily handled in air. Its rhodium(I) complex exhibits very high enantioselectivities and catalytic activities in the asymmetric hydrogenation of functionalized alkenes.
- Sawatsugawa, Yuuki,Tamura, Ken,Sano, Natsuhiro,Imamoto, Tsuneo
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supporting information
p. 8874 - 8878
(2019/11/03)
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- Generation of amine dehydrogenases with increased catalytic performance and substrate scope from ε-deaminating L-Lysine dehydrogenase
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Amine dehydrogenases (AmDHs) catalyse the conversion of ketones into enantiomerically pure amines at the sole expense of ammonia and hydride source. Guided by structural information from computational models, we create AmDHs that can convert pharmaceutically relevant aromatic ketones with conversions up to quantitative and perfect chemical and optical purities. These AmDHs are created from an unconventional enzyme scaffold that apparently does not operate any asymmetric transformation in its natural reaction. Additionally, the best variant (LE-AmDH-v1) displays a unique substrate-dependent switch of enantioselectivity, affording S- or R-configured amine products with up to >99.9% enantiomeric excess. These findings are explained by in silico studies. LE-AmDH-v1 is highly thermostable (Tm of 69 °C), retains almost entirely its catalytic activity upon incubation up to 50 °C for several days, and operates preferentially at 50 °C and pH 9.0. This study also demonstrates that product inhibition can be a critical factor in AmDH-catalysed reductive amination.
- Tseliou, Vasilis,Knaus, Tanja,Masman, Marcelo F.,Corrado, Maria L.,Mutti, Francesco G.
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- Structural Investigations on Enantiopure P–OP Ligands: A High-Performing P–OP Ligand for Rhodium-Catalysed Hydrogenations
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A second generation of phosphine–phosphite (P–OP) ligands, incorporating a more sterically bulky phosphite group than previous P–OP ligand designs, gave very efficient catalysts for the Rh-catalysed asymmetric hydrogenation of a diverse array of substrate
- Fernández-Pérez, Héctor,Balakrishna, Bugga,Vidal-Ferran, Anton
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p. 1525 - 1532
(2018/04/20)
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- Imidazolium chloride: An efficient catalyst for transamidation of primary amines
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A highly efficient and convenient protocol of imidazolium chloride (30 mol %) catalyzed amidation of amines with moderate to excellent yields was reported. The protocol shows broad substrate scope for aromatic, aliphatic, and heterocyclic primary amines.
- Tian, Qingqiang,Gan, Zongjie,Wang, Xuetong,Li, Dan,Luo, Wen,Wang, Huajun,Dai, Zeshu,Yuan, Jianyong
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supporting information
(2018/09/10)
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- Asymmetric Synthesis of Chiral Primary Amines by Ruthenium-Catalyzed Direct Reductive Amination of Alkyl Aryl Ketones with Ammonium Salts and Molecular H2
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A ruthenium/C3-TunePhos catalytic system has been identified for highly efficient direct reductive amination of simple ketones. The strategy makes use of ammonium acetate as the amine source and H2 as the reductant and is a user-friendly and operatively simple access to industrially relevant primary amines. Excellent enantiocontrol (>90% ee for most cases) was achieved with a wide range of alkyl aryl ketones. The practicability of this methodology has been highlighted by scalable synthesis of key intermediates of three drug molecules. Moreover, an improved synthetic route to the optimal diphosphine ligand C3-TunePhos is also presented.
- Tan, Xuefeng,Gao, Shuang,Zeng, Weijun,Xin, Shan,Yin, Qin,Zhang, Xumu
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p. 2024 - 2027
(2018/02/19)
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- Method for synthesis of (R)-1-(4-methyl phenyl) ethylamine
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The invention discloses a method for synthesis of (R)-1-(4-methyl phenyl) ethylamine. The method includes: subjecting a compound 3 to deacylation to obtain (R)-1-(4-methyl phenyl) ethylamine in a C4-C10 monoalcohol solvent and in the presence of alkali metal hydroxide, wherein R refers to ethanoyl, propionyl or butyryl. The method is low in synthesis cost, simple in step, safe in operation, low inby-products, simple in aftertreatment, easy to purify intermediate products and final products, high in whole yield, high in final product purity and easy in industrialization.
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Paragraph 0103; 0105-0106
(2018/11/03)
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- Asymmetric Allylic Alkylation and Hydrogenation with Transition Metal Complexes of Diphosphite Ligands Based on (1S,2S)-Trans-1,2-cyclohexanediol
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Abstract: The preparation of new palladium complexes in situ that were composed of a series of chiral diphosphite ligands, which were derived from (1S,2S)-trans-1,2-cyclohexanediol, have been described. It was found that (1S,2S)-bis[(S)-1,1′-binaphthyl-2,
- Pang, Zengbo,Tian, Mi,Li, Haifeng,Wang, Lailai
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p. 893 - 899
(2017/03/24)
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- P-Stereogenic bisphosphines with a hydrazine backbone: From N-N atropoisomerism to double nitrogen inversion
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The synthesis of P-stereogenic bisphosphine ligands starting from a phosphinous acid chiral synthon and hydrazine is reported. The dialkylation of the hydrazine backbone yielded atropo- and nitrogen inversion isomers which are in slow exchange. The crysta
- Prades, Amparo,Nú?ez-Pertí?ez, Samuel,Riera, Antoni,Verdaguer, Xavier
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supporting information
p. 4605 - 4608
(2017/04/28)
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- Bidentate Phosphine–Phosphoramidite Ligands of the BettiPhos Family for Rh-Catalyzed Asymmetric Hydrogenation
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Phosphine–phosphoramidites comprising a stereogenic phosphorus atom at the phosphoramidite moiety and a Betti base as chiral backbone have been synthesized. Individual diastereomers have been benchmarked as ligands in the Rh-catalyzed asymmetric hydrogenation of dimethyl itaconate to study the interplay of the different elements of chirality. The privileged diastereomer was applied to Rh-catalyzed asymmetric hydrogenation of several functionalized olefins, leading to high enantioselectivities between 91 and 97 % ee, which confirms the effectiveness of the BettiPhos ligand family in asymmetric catalysis.
- Schmitz, Christian,Holthusen, Katharina,Leitner, Walter,Franciò, Giancarlo
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p. 4111 - 4116
(2017/08/07)
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- Amine dehydrogenases: Efficient biocatalysts for the reductive amination of carbonyl compounds
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Amines constitute the major targets for the production of a plethora of chemical compounds that have applications in the pharmaceutical, agrochemical and bulk chemical industries. However, the asymmetric synthesis of α-chiral amines with elevated catalytic efficiency and atom economy is still a very challenging synthetic problem. Here, we investigated the biocatalytic reductive amination of carbonyl compounds employing a rising class of enzymes for amine synthesis: amine dehydrogenases (AmDHs). The three AmDHs from this study-operating in tandem with a formate dehydrogenase from Candida boidinii (Cb-FDH) for the recycling of the nicotinamide coenzyme-performed the efficient amination of a range of diverse aromatic and aliphatic ketones and aldehydes with up to quantitative conversion and elevated turnover numbers (TONs). Moreover, the reductive amination of prochiral ketones proceeded with perfect stereoselectivity, always affording the (R)-configured amines with more than 99% enantiomeric excess. The most suitable amine dehydrogenase, the optimised catalyst loading and the required reaction time were determined for each substrate. The biocatalytic reductive amination with this dual-enzyme system (AmDH-Cb-FDH) possesses elevated atom efficiency as it utilizes the ammonium formate buffer as the source of both nitrogen and reducing equivalents. Inorganic carbonate is the sole by-product.
- Knaus, Tanja,B?hmer, Wesley,Mutti, Francesco G.
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p. 453 - 463
(2017/08/14)
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- Isopropyl 2-ethoxyacetate—an efficient acylating agent for lipase-catalyzed kinetic resolution of amines in batch and continuous-flow modes
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Productivity [conversion (c) and specific reaction rate (rbatchor rflow)] and enantiomer selectivity [enantiomeric ratio (E) and enantiomeric excess (ee) of the products] of ethyl and isopropyl esters of acetic, 2-methoxyacetic and 2-ethoxyacetic acids as acylating agents were compared in the N-acylation of (±)-1-phenylethanamine rac-1 catalyzed by variously immobilized forms of Candida antarctica lipase B (CaLB) using shake flasks and continuous-flow reactors. The effect of the temperature in the 0–80 °C range on productivity and enantiomer selectivity in KRs of rac-1 was investigated with the isopropyl esters in continuous-flow mode using CaLB-filled minireactors. Isopropyl 2-ethoxyacetate surpassed the performance of ethyl 2-methoxyacetate in terms of both productivity (1.9–2.9 times higher rate in batch mode) and enantiomeric selectivity (ee(R)-amide>99.9% compared to 99.8%) providing at 40 °C high volumetric productivity (2.22 kg L?1h?1), specific reaction rate and enantiomeric excess (rflow=783 μmol min?1g?1, ee(R)-2c>99.9%).
- Oláh, Márk,Boros, Zoltán,Hornyánszky, Gábor,Poppe, László
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p. 7249 - 7255
(2016/10/26)
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- Organocatalytic Kinetic Resolution of Sulfoximines
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An efficient kinetic resolution of sulfoximines with enals was realized using chiral N-heterocyclic carbene (NHC) catalysts. The stereoselective amidation proceeds without additional acyl transfer agent. Both enantiomers of the sulfoximines can be obtaine
- Dong, Shunxi,Frings, Marcus,Cheng, Hanchao,Wen, Jian,Zhang, Duo,Raabe, Gerhard,Bolm, Carsten
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supporting information
p. 2166 - 2169
(2016/03/05)
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- Chiroptical Asymmetric Reaction Screening via Multicomponent Self-Assembly
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Self-assembly of a stereodynamic phosphine ligand, Pd(II), and a chiral amine, amino alcohol, or amino acid generates characteristic UV and CD signals that can be used for quantitative stereochemical analysis of the bound substrate. A robust mix-and-measure chiroptical sensing protocol has been developed and used to determine the absolute configuration, ee, and yield of an amine produced by Ir-catalyzed asymmetric hydrogenation of an iminium salt. The analysis requires only 1 mg of the crude reaction mixture and minimizes cost, labor, time, and waste.
- De Los Santos, Zeus A.,Wolf, Christian
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p. 13517 - 13520
(2016/10/31)
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- A Single Lipase-Catalysed One-Pot Protocol Combining Aminolysis Resolution and Aza-Michael Addition: An Easy and Efficient Way to Synthesise β-Amino Acid Esters
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A novel one-pot protocol combining aza-Michael addition and aminolysis resolution was developed to obtain chiral β-amino acid esters with lipase B from Candida antarctica (CAL-B) as the only catalyst. This method is conducted under mild reaction conditions and is very easy to handle. After a series of detailed optimization studies, ten racemic aromatic or aliphatic amines were subjected to this one-pot procedure, and twelve chiral β-amino acid esters and ten chiral amides were successfully synthesised with excellent ee values in theoretical yields. Scaled-up procedures also worked without apparent reduction in reaction rate or enantioselectivity, which makes this method suitable for large-scale production of chiral β-amino acid esters. A one-pot protocol for simultaneous synthesis of chiral β-amino acid esters and amides was developed by combining single lipase B from Candida antarctica (CAL-B) catalysed aza-Michael addition and aminolysis resolution. This method requires mild reaction conditions and is very easy to handle. Chiral β-amino acid esters and chiral amides were obtained with excellent ee values and in theoretical yields.
- Xu, Fan,Wu, Qiongsi,Chen, Xiaoyang,Lin, Xianfu,Wu, Qi
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supporting information
p. 5393 - 5401
(2015/08/24)
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- Chiral diphosphites derived from (1R,2R)-trans-1,2-cyclohexanediol: A new class of ligands for asymmetric hydrogenations
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A series of novel chiral diphosphite ligands was easily prepared in a few steps from commercial (1R,2R)-trans-1,2-cyclohexanediol as the chiral source, and successfully employed in the Rh-catalyzed asymmetric hydrogenation of α,β-unsaturated carboxylic ac
- Pang, Zeng-Bo,Li, Hai-Feng,Tian, Mi,Wang, Lai-Lai
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p. 1389 - 1393
(2015/12/09)
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- Enantiomeric enrichments via the self-disproportionation of enantiomers (SDE) by achiral, gravity-driven column chromatography: A case study using N-(1-phenylethyl)acetamide for optimizing the enantiomerically pure yield and magnitude of the SDE
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This work explores the self-disproportionation of enantiomers (SDE) via achiral, gravity-driven column chromatography as typically used in laboratory settings for the purpose of enantiomeric enrichment using N-(1-phenylethyl)acetamide (PEA) as a case stud
- Wzorek, Alicja,Sato, Azusa,Drabowicz, J?zef,Soloshonok, Vadim A.,Klika, Karel D.
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p. 1147 - 1159
(2015/08/24)
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- Carbohydrate base co-polymers as an efficient immobilization matrix to enhance lipase activity for potential biocatalytic applications
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In the present study, we have synthesized biocompatible hybrid blend of cellulosic polymers of hydroxypropyl-methyl-cellulose (HPMC) and chitosan (CHY) for the immobilization of Candida rugosa lipase (CRL). The immobilized biocatalyst HPMC:CHY:CRL was subjected for characterization such as SEM, TGA, water content analysis, lipase activity, specific activity and protein content analysis. The kinetic parameter study (Rmax/Km) demonstrated improved biocatalytic activity of lipase after immobilization on carbohydrate co-polymers of HPMC:CHY. This biocatalyst was then employed to study practical biocatalytic applications for kinetic resolution which provided 50% conversion and >94% enantiomeric excess of substrate/product (ees/eep). The protocol demonstrated excellent recyclability upto five cycles. Finally, we studied influence of immobilization on cellulosic polymers for substrate, structure and reactivity for kinetic resolution. Hence, we investigated R0 (initial reaction rate), E-value (enantioselectivity) and Ea (activation energy). This study confirms that, lipase immobilized on carbohydrate polymers had 3-4 folds higher biocatalytic activity as compared to crude CRL.
- Badgujar, Kirtikumar Chandulal,Bhanage, Bhalchandra Mahadeo
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p. 709 - 717
(2015/09/02)
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- A dual-catalysis anion-binding approach to the kinetic resolution of amines: Insights into the mechanism via a combined experimental and computational study
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Racemic benzylic amines undergo kinetic resolution via benzoylation with benzoic anhydride in the presence of a dual catalyst system consisting of a readily available amide-thiourea catalyst and 4-dimethylaminopyridine (DMAP). An evaluation of various exp
- Mittal, Nisha,Lippert, Katharina M.,De, Chandra Kanta,Klauber, Eric G.,Emge, Thomas J.,Schreiner, Peter R.,Seidel, Daniel
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supporting information
p. 5748 - 5758
(2015/05/20)
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- Sporopollenin as an efficient green support for covalent immobilization of a lipase
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Sporopollenin exine capsules (SECs), derived from the spores of Lycopodium clavatum, have been functionalised with 1,n-diamines and the resulting aminoalkyl microcapsules used to immobilize Candida antarctica lipase B (Cal B) via a glutaradehyde-based diimine covalent linker. The supported enzyme efficiently catalyzes the esterification of oleic acid with ethanol. Initial rates using the SEC-CalBs were comparable to the commercial enzyme Novozym 435, but displayed up to 20-fold higher specific activity. The supported enzymes could also be recycled and after four cycles displayed only a modest decrease in conversions. In a kinetic resolution the SEC-CalBs efficiently acetylated rac-1-phenylethanol, with conversions up to 37% after 5 hours and product enantiomeric excesses of >99%. Related to this, the dynamic resolution of rac-1-phenylethylamine, in the presence of Pd-BaSO4 and ammonium formate, led to the acetylated amine with a 94% conversion and >99% ee.
- De Souza, Stefania P.,Bassut, Jonathan,Marquez, Heiddy V.,Junior, Ivaldo I.,Miranda, Leandro S. M.,Huang, Youkui,Mackenzie, Grahame,Boa, Andrew N.,De Souza, Rodrigo O. M. A.
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p. 3130 - 3136
(2015/06/08)
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- An organocatalytic biomimetic approach to α-aminophosphonates
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A novel biomimetic approach to optically active α-aminophosphonates utilizing readily available acylphosphonates and 2-chlorobenzylamine as starting materials has been described. The enantioselective protonation constitutes the main enantiodifferentiating step in the developed strategy. This nature-inspired approach proceeds efficiently and in a highly stereoselective manner. This journal is
- Kowalczyk, Dorota,Albrecht, Lukasz
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supporting information
p. 3981 - 3984
(2015/03/30)
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- 1,1-P-OP ligands with P-stereogenic phosphino groups in asymmetric hydrogenations and hydroformylations
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A new series of narrow-bite-angle phosphine-phosphite (1,1-P-OP) ligands (3a-d) has been efficiently prepared from the enantiopure (SP)-tert- butyl(hydroxymethyl)methylphosphino borane complex 1, a crucial intermediate. The catalytic performance of the ligands in Rh-mediated asymmetric hydrogenations and hydroformylations is described. The corresponding rhodium complexes provided excellent efficiencies (full conversion in all cases) and high enantioselectivities (up to 98% ee) for the asymmetric hydrogenation of structurally diverse functionalized alkenes. Furthermore, rhodium catalysts derived from these 1,1-P-OP ligands were highly active and gave excellent regioselectivities (branched/linear product ratios of up to 97/3) and moderate enantioselectivities in the hydroformylation of different terminal olefins.
- Lao, Joan R.,Benet-Buchholz,Vidal-Ferran, Anton
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p. 2960 - 2963
(2014/07/08)
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- Enantiopure narrow bite-angle P-OP ligands: Synthesis and catalytic performance in asymmetric hydroformylations and hydrogenations
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Herein is reported the preparation of a set of narrow bite-angle P-OP ligands the backbone of which contains a stereogenic carbon atom. The synthesis was based on a Corey-Bakshi-Shibata (CBS)-catalyzed asymmetric reduction of phosphomides. The structure of the resulting 1,1-P-OP ligands, which was selectively tuned through adequate combination of the configuration of the stereogenic carbon atom, its substituent, and the phosphite fragment, proved crucial for providing a rigid environment around the metal center, as evidenced by X-ray crystallography. These new ligands enabled very good catalytic properties in the Rh-mediated enantioselective hydrogenation and hydroformylation of challenging and model substrates (up to 99 % ee). Whereas for asymmetric hydrogenation the optimal P-OP ligand depended on the substrate, for hydroformylation, a single ligand was the highest-performing one for almost all studied substrates: it contains an R-configured stereogenic carbon atom between the two phosphorus ligating groups, and an S-configured 3,3′-diphenyl-substituted biaryl unit. Ligand design: Narrow-bite-angle P-OP ligands incorporating a stereogenic carbon atom in their backbone have been synthesized by Corey-Bakshi-Shibata (CBS)-catalyzed asymmetric reduction of the corresponding intermediates followed by O-phosphorylation. Rhodium complexes of these ligands provided very good catalytic performance in hydroformylations and hydrogenations (see scheme).
- Fernández-Pérez, Héctor,Benet-Buchholz, Jordi,Vidal-Ferran, Anton
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p. 15375 - 15384
(2016/02/18)
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- Rh-catalyzed asymmetric hydrogenation using a furanoside monophosphite second-generation ligand library: Scope and limitations
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The ligand design of one of the most successful monophosphite ligand classes in Rh-catalyzed hydrogenation was expanded upon by introducing several substituents at the C-3 position of the furanoside backbone. A small but structurally important library of
- Alegre, Sabina,Alberico, Elisabetta,Pamies, Oscar,Dieguez, Montserrat
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p. 258 - 262
(2014/03/21)
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- Transaminases applied to the synthesis of high added-value enantiopure amines
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Critical parameters affecting the stereoselective amination of (hetero)aromatic ketones using transaminases have been studied, such as temperature, pH, substrate concentration, cosolvent, and source and percentage of amino donor, to further optimize the production of enantiopure amines using both (S)- and (R)-selective biocatalysts from commercial suppliers. Interesting enantiopure amino building blocks have been obtained, overcoming some limitations of traditional chemical synthetic methods. Representative processes were scaled up, affording halogenated and heteroaromatic amines in enantiomerically pure form and good isolated yields.
- Paul, Caroline E.,Rodriguez-Mata, Maria,Busto, Eduardo,Lavandera, Ivan,Gotor-Fernandez, Vicente,Gotor, Vicente,Garcia-Cerrada, Susana,Mendiola, Javier,De Frutos, Oscar,Collado, Ivan
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p. 788 - 792
(2014/07/08)
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- Enantioselective synthesis of (R)-2-arylpropanenitriles catalysed by ene-reductases in aqueous media and in biphasic ionic liquid-water systems
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The enantioselective reduction of α-methylene nitrile derivatives catalysed by ene-reductases affords the corresponding (R)-2-arylpropanenitriles with high conversion values. The reaction is investigated either in aqueous medium (with an organic cosolvent or by loading the substrate onto hydrophobic resins) or in a biphasic ionic liquid-water system. The use of ionic liquids, herein with isolated ene-reductases, is found to improve the work-up and the substrate recovery method. The synthetic manipulation of the final chiral nitrile derivatives indicates how this biocatalysed method can be exploited for the preparation of a wide range of chiral compounds.
- Brenna, Elisabetta,Crotti, Michele,Gatti, Francesco G.,Manfredi, Alessia,Monti, Daniela,Parmeggiani, Fabio,Santangelo, Sara,Zampieri, Davila
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p. 2425 - 2431
(2014/08/18)
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- How the mode of Candida antarctica lipase B immobilization affects the continuous-flow kinetic resolution of racemic amines at various temperatures
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The effect of temperature on enantiomeric ratio (E) and specific reaction rate (rflow) in the continuous-flow mode acetylation of (±)-1-phenylethanamine (rac-1a), (±)-4-phenylbutan-2-amine (rac-1b) and (±)-1,2,3,4-tetrahydro-1-naphthalenamine (rac-1c) by variously immobilized Candida antarctica lipase B biocatalysts was studied in the 0-70 °C range. In the continuous-flow kinetic resolutions with differently immobilized CaLB biocatalysts, the character of temperature effect depended significantly both on the substrate and on the mode of immobilization. Alteration of E in the kinetic resolutions of three differently flexible amines rac-1a-c as a function of temperature was rationalized by the various flexibility of the lipase in its different forms. Our results indicated that the optimal method of immobilization depended both on the nature of the substrate and the reaction conditions.
- Boros, Zoltán,Falus, Péter,Márkus, Mária,Weiser, Diána,Oláh, Márk,Hornyánszky, Gábor,Nagy, József,Poppe, László
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p. 119 - 125
(2013/01/15)
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- Small bite-angle P-OP ligands for asymmetric hydroformylation and hydrogenation
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A series of small bite-angle phosphine-phosphite (P-OP) ligands have been synthesized by a two-step method. The key intermediate was prepared by an unprecedented asymmetric carbonyl reduction of a phosphamide using the CBS (Corey-Bakshi-Shibata) catalyst. The topology of these ligands (a configurationally stable stereogenic carbon with two heteroatom substituents) and their small bite-angle (created by the close proximity of the two ligating groups to the metal center) together provide a rigid asymmetric environment around this center, enabling high stereoselectivity in hydroformylations and hydrogenations of standard substrates.
- Fernandez-Perez, Hector,Benet-Buchholz,Vidal-Ferran, Anton
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supporting information
p. 3634 - 3637
(2013/08/23)
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- Rhodium-catalyzed asymmetric olefin hydrogenation by easily accessible aniline- and pyridine-derived chiral phosphites
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An aniline- and two pyridine-derived (R)-BINOL-based P,N-containing phosphite ligands have been synthesized via a one-pot procedure. Treatment of the aniline-derived ligand with 1 equiv of [Rh(COD)2]BF4 yielded a mixture of a P,N-che
- Vallianatou, Kalliopi A.,Frank, Dominik J.,Antonopoulou, Georgia,Georgakopoulos, Spyros,Siapi, Eleni,Zervou, Maria,Kostas, Ioannis D.
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p. 397 - 401
(2013/02/23)
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- Ph-tetrame-bithienine, the first member of the class of chiral heterophosphepines: Synthesis, electronic and steric properties, metal complexes and catalytic activity
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Unknown 1H-2,7-dihydro-1-phenylphosphepine, containing a 2,2,5,5-tetramethyl-3,3-bithiophene atropisomeric scaffold (Ph-tetraMe- Bithienine), and its oxide have been synthesized and structurally characterized by single-crystal X-ray diffraction analysis.
- Vaghi, Luca,Benincori, Tiziana,Cirilli, Roberto,Alberico, Elisabetta,Mussini, Patrizia Romana,Pierini, Marco,Pilati, Tullio,Rizzo, Simona,Sannicolo, Francesco
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p. 8174 - 8184
(2014/01/06)
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- Synthesis of heterogeneous enzyme-metal nanoparticle biohybrids in aqueous media and their applications in C-C bond formation and tandem catalysis
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The straightforward synthesis of novel enzyme-metalNP nanobiohybrids in aqueous medium was developed. These new nanobiohybrids were excellent multivalent catalysts combining both activities in various sets of synthetic reactions even at ultra-low concentrations (ppb amount).
- Filice, Marco,Marciello, Marzia,Morales, Maria Del Puerto,Palomo, Jose M.
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p. 6876 - 6878
(2013/07/26)
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- Shvo's catalyst in chemoenzymatic dynamic kinetic resolution of amines-inner or outer sphere mechanism?
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Evidence is provided for the inner-sphere mechanism with actual metal coordination of the racemic amine in the crucial hydrogen transfer step promoted by Shvo's catalyst of the chemoenzymatic dynamic kinetic resolution (DKR) of amines. Key intermediates i
- Vaz, Boniek G.,Milagre, Cintia D. F.,Eberlin, Marcos N.,Milagre, Humberto M. S.
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supporting information
p. 6695 - 6698
(2013/10/01)
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- Ethyl acetate as an acyl donor in the continuous flow kinetic resolution of (±)-1-phenylethylamine catalyzed by lipases
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The synthesis of chiral amines is still a challenge for organic synthesis since optically pure amines are of great importance for the pharmaceutical and agrochemical industries. Among all the methodologies developed until now, chemoenzymatic dynamic kinetic resolution has proven to be useful for the preparation of enantioenriched primary chiral amines. In our continuous efforts toward the development of a continuous flow process, herein we report our results on the continuous flow kinetic resolution of (±)-1- phenylethylamine leading to the desired products with high enantiomeric ratios (>200) and short residence times (40 minutes) using ethyl acetate as the acyl donor.
- De Miranda, Amanda S.,Miranda, Leandro S. M.,De Souza, Rodrigo O. M. A.
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supporting information
p. 3332 - 3336
(2013/06/05)
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- Asymmetric synthesis of nonracemic primary amines via spiroborate-catalyzed reduction of pure (E)- and (Z)-O-benzyloximes: Applications toward the synthesis of calcimimetic agents
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Highly enantiopure (1-aryl)- and (1-naphthyl)-1-ethylamines were synthesized by the borane-mediated reduction of single-isomeric (E)- and (Z)-O-benzyloxime ethers using the stable spiroborate ester derived from (S)-diphenyl valinol and ethylene glycol as the chiral catalyst. Primary (R)-arylethylamines were prepared by the reduction of pure (Z)-ethanone oxime ethers in up to 99% ee using 15% of catalyst. Two convenient and facile approaches to the synthesis of new and known calcimimetic analogues employing enantiopure (1-naphthalen-1-yl)ethylamine as chiral precursor are described.
- Ou, Wenhua,Espinosa, Sandraliz,Meléndez, Héctor J.,Farré, Silvia M.,Alvarez, Jaime L.,Torres, Valerie,Martínez, Ileanne,Santiago, Kiara M.,Ortiz-Marciales, Margarita
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p. 5314 - 5327
(2013/07/25)
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- Chiral phosphoric acid-catalyzed oxidative kinetic resolution of indolines based on transfer hydrogenation to imines
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The oxidative kinetic resolution of 2-substituted indoline derivatives was achieved by hydrogen transfer to imines by means of a chiral phosphoric acid catalyst. The oxidative kinetic resolution was applicable to racemic alkyl- or aryl-substituted indolines, and the remaining indolines were obtained in good yields with excellent enantioselectivities.
- Saito, Kodai,Shibata, Yukihiro,Yamanaka, Masahiro,Akiyama, Takahiko
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p. 11740 - 11743
(2013/09/02)
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- Hydrophobic adsorption and covalent immobilization of Candida antarctica lipase B on mixed-function-grafted silica gel supports for continuous-flow biotransformations
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Adsorption onto solid supports has proven to be an easy and effective way to improve the mechanical and catalytic properties of lipases. Covalent binding of lipases onto the support surface enhances the active lifetime of the immobilized biocatalysts. Our study indicates that mesoporous silica gels grafted with various functions are ideal supports for both adsorptive and covalent binding for lipase B from Candida antarctica (CaLB). Adsorption of CaLB on phenyl-functionalized silica gels improved in particular its specific activity, whereas adsorption on aminoalkyl-modified silica gels enabling covalent binding with the proper reagents resulted in only moderate specific activity. In addition, adsorption on silica gels modified by mixtures of phenyl- and aminoalkyl silanes significantly increased the productivity of CaLB. Furthermore, CaLB adsorbed onto a phenyl/aminoalkyl-modified surface and then treated with glutardialdehyde (GDA) as cross-linking agent provided a biocatalyst of enhanced durability. Adsorbed and cross-linked CaLB was resistant to detergent washing that would otherwise physically deactivate adsorbed CaLB preparations. The catalytic properties of our best immobilized CaLB variants, including temperature-dependent behavior were compared between 0 and 70 C with those of two commercial CaLB biocatalysts in the continuous-flow kinetic resolutions of racemic 1-phenylethanol rac-1a and 1-phenylethanamine rac-1b.
- Boros, Zoltán,Weiser, Diána,Márkus, Mária,Abaháziová, Emese,Magyar, ágnes,Tomin, Anna,Koczka, Béla,Kovács, Péter,Poppe, László
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p. 1039 - 1047
(2013/07/26)
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- Nickel nanoparticles as racemization catalysts for primary amines
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By combining bases that are known to racemize benzylic amines with a nickel(II) salt, active nickel nanoparticles were obtained that can be used as catalysts in the racemization of both aliphatic and benzylic primary amines. The nanoparticles are stable in the ionic liquid tetrabutylammonium bromide and can complete most racemizations within a few hours with excellent selectivity. The problem of the incompatibility of the strongly reducing racemization catalyst and the enzymatic amine resolution catalyst was overcome by using a two-pot system with a biphasic racemization step. Consecutive contact of a nonane layer that contained the amine with the acylating enzyme and with the racemizing Ni nanoparticles in the ionic liquid allowed the 50 % amide yield limit of a kinetic resolution to be successfully surpassed. Copyright
- Geukens, Inge,Plessers, Eva,Seo, Jin Won,De Vos, Dirk E.
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supporting information
p. 2623 - 2628
(2013/07/11)
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- Rhodium-catalyzed enantioselective hydrogenation of oxime acetates
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Rh-catalyzed enantioselective hydrogenation of oxime acetates was first reported, which afforded a new approach for chiral amine synthesis.
- Huang, Kexuan,Li, Shengkun,Chang, Mingxin,Zhang, Xumu
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supporting information
p. 484 - 487
(2013/03/29)
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- Efficient enzymatic amine resolution at high substrate input using diethyl malonate as an acyl donor of low hazard potential
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Diethyl malonate turned out to be both a green and highly efficient acyl donor in the lipase-catalyzed resolution of amines, thus representing an attractive alternative to currently applied acyl donors. By means of this acyl donor a highly efficient enzymatic process for the resolution of amines, running at high substrate input of up to 200 g/L in an organic solvent classified as usable according to the Pfizer Solvent Selection Guide, is presented.
- Simon, Sabine,Groeger, Harald,Osswald, Steffen,Roos, Juergen
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p. 1123 - 1126,4
(2020/09/16)
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- Rigid P-chiral phosphine ligands with tert -butylmethylphosphino groups for rhodium-catalyzed asymmetric hydrogenation of functionalized alkenes
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Both enantiomers of 2,3-bis(tert-butylmethylphosphino)quinoxaline (QuinoxP*), 1,2-bis(tert-butylmethylphosphino)benzene (BenzP*), and 1,2-bis(tert-butylmethylphosphino)-4,5-(methylenedioxy)benzene (DioxyBenzP*) were prepared in short steps from enantiopure (S)- and (R)-tert-butylmethylphosphine-boranes as the key intermediates. All of these ligands were crystalline solids and were not readily oxidized on exposure to air. Their rhodium complexes exhibited excellent enantioselectivities and high catalytic activities in the asymmetric hydrogenation of functionalized alkenes, such as dehydroamino acid derivatives and enamides. The practical utility of these catalysts was demonstrated by the efficient preparation of several chiral pharmaceutical ingredients having an amino acid or a secondary amine component. A rhodium complex of the structurally simple ligand BenzP* was used for the mechanistic study of asymmetric hydrogenation. Low-temperature NMR studies together with DFT calculations using methyl α-acetamidocinnamate as the standard model substrate revealed new aspects of the reaction pathways and the enantioselection mechanism.
- Imamoto, Tsuneo,Tamura, Ken,Zhang, Zhenfeng,Horiuchi, Yumi,Sugiya, Masashi,Yoshida, Kazuhiro,Yanagisawa, Akira,Gridnev, Ilya D.
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supporting information; experimental part
p. 1754 - 1769
(2012/03/11)
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- Rhodium-catalyzed asymmetric hydrogenation of olefins with PhthalaPhos, a new class of chiral supramolecular ligands
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A library of 19 binol-derived chiral monophosphites that contain a phthalic acid diamide group (Phthala- Phos) has been designed and synthesized in four steps. These new ligands were screened in the rhodium-catalyzed enantioselective hydrogenation of prochiral dehydroamino esters and enamides. Several members of the library showed excellent enantioselectivity with methyl 2-acetamido acrylate (6 ligands gave >97% ee), methyl (Z)-2- acetamido cinnamate (6 ligands gave >94% ee), and N-(1-phenylvinyl)acetamide (9 ligands gave >95% ee), whilst only a few representatives afforded high enantioselectivities for challenging and industrially relevant substrates N-(3,4-dihydronaphthalen-1- yl)-acetamide (96% ee in one case) and methyl (E)-2-(acetamidomethyl)-3- phenylacrylate (99% ee in one case). In most cases, the new ligands were more active and more stereoselective than their structurally related monodentate phosphites (which are devoid of functional groups that are capable of hydrogen-bonding interactions). Control experiments and kinetic studies were carried out that allowed us to demonstrate that hydrogen-bonding interactions involving the diamide group of the PhthalaPhos ligands strongly contribute to their outstanding catalytic properties. Computational studies carried out on a rhodium precatalyst and on a conceivable intermediate in the hydrogenation catalytic cycle shed some light on the role played by hydrogen bonding, which is likely to act in a substrate-orientation effect.
- Pignataro, Luca,Boghi, Michele,Civera, Monica,Carboni, Stefano,Piarulli, Umberto,Gennari, Cesare
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supporting information; experimental part
p. 1383 - 1400
(2012/03/27)
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- A library approach to the development of BenzaPhos: Highly efficient chiral supramolecular ligands for asymmetric hydrogenation
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A library of chiral supramolecular ligands, named BenzaPhos, of straightforward preparation (two steps from commercially or readily available starting materials) and modular structure, was designed and synthesized. The ligands were screened in the search for new rhodium catalysts for the enantioselective hydrogenation of several benchmark and industrially relevant substrates. Once a series of hits were identified, structural modifications were introduced on three of the best ligands and a small second-generation library was created. Members of the latter library showed outstanding levels of activity and enantioselectivity in the hydrogenation of challenging olefins, such as enamide S4 and β-dehydroamino ester S5 (>99 % ee: best value ever reported in both cases). A series of control experiments were undertaken to clarify the role of hydrogen bonding in determining the catalytic properties of the new ligands. The results of these experiments, together with those of computational studies carried out on four dihydride complexes involved in the catalytic hydrogenation of substrate S4, strongly suggest that a substrate orientation takes place in the catalytic cycle by formation of a hydrogen bond between the ligand amide oxygen atom and the substrate amide NH atom. As simple as selective: BenzaPhos ligands, benzamide-containing chiral monophosphites of modular structure and trivial synthesis, have been screened in the Rh-catalyzed hydrogenation of olefins (see scheme), giving excellent enantioselectivities with three benchmark and two industrially relevant substrates. Control experiments and computational studies suggest an important role of ligand-substrate hydrogen bonding in the stereodiscriminating step of the catalytic cycle. Copyright
- Pignataro, Luca,Bovio, Chiara,Civera, Monica,Piarulli, Umberto,Gennari, Cesare
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supporting information; experimental part
p. 10368 - 10381
(2012/10/08)
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- Modular P-OP ligands in rhodium-mediated asymmetric hydrogenation: A comparative catalysis study
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Highly efficient and enantioselective hydrogenation reactions for α-(acylamino)acrylates, itaconic acid derivatives and analogues, α-substituted enol ester derivatives, and α-arylenamides (25 substrates) catalyzed by chiral cationic rhodium complexes of a set of P-OP ligands have been developed. The catalytic systems derived from these P-OP ligands provided a straightforward access to enantiomerically enriched α-amino acid, carboxylic acid, amine, and alcohol derivatives that are valuable chiral building blocks. Excellent efficiencies (full conversion in all cases) and extremely high enantiomeric excesses (94-99% ee) were achieved for a wide range of α-substituted enol ester derivatives, regardless of the substitution pattern. The R-oxy group of the ligand (methoxy or triphenylmethoxy) strongly influences the enantioselectivity and catalytic activity. Greater steric bulk around the metal centre correlated to greater (or similar) enantioselectivity, but also to slower hydrogenation. Furthermore, the hydrogenation rates observed with the four model substrates follow the same trend, independently of the R-oxy group of the ligand: methyl 2-acetamidoacrylate>dimethyl itaconate>1-phenylvinyl acetate>N-(1- phenylvinyl)acetamide. A substrate-to-catalyst ratio (S/C) of up to 10,000:1 was sufficient for total hydrogenation of a model substrate of intermediate reactivity (dimethyl itaconate), and did not imply any loss in conversion or enantioselectivity. Copyright
- Nunez-Rico, Jose L.,Etayo, Pablo,Fernandez-Perez, Hector,Vidal-Ferran, Anton
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supporting information
p. 3025 - 3035
(2013/01/15)
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- Asymmetric Rh-catalyzed hydrogenation using a furanoside phosphite-phosphoroamidite and diphosphoroamidite ligand library
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A furanoside phosphite-phosphoroamidite and diphosphoroamidite ligand library L1-L5a-f was tested in the asymmetric Rh-catalyzed hydrogenation of α,β-unsaturated carboxylic acid derivatives and enamides. Enantioselectivity depended strongly on the ligand
- Coll, Mercedes,Pamies, Oscar,Dieguez, Montserrat
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experimental part
p. 3038 - 3045
(2012/04/10)
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