- Cinchona-Alkaloid-Derived NNP Ligand for Iridium-Catalyzed Asymmetric Hydrogenation of Ketones
-
Most ligands applied for asymmetric hydrogenation are synthesized via multistep reactions with expensive chemical reagents. Herein, a series of novel and easily accessed cinchona-alkaloid-based NNP ligands have been developed in two steps. By combining [Ir(COD)Cl]2, 39 ketones including aromatic, heteroaryl, and alkyl ketones have been hydrogenated, all affording valuable chiral alcohols with 96.0-99.9% ee. A plausible reaction mechanism was discussed by NMR, HRMS, and DFT, and an activating model involving trihydride was verified.
- Zhang, Lin,Zhang, Ling,Chen, Qian,Li, Linlin,Jiang, Jian,Sun, Hao,Zhao, Chong,Yang, Yuanyong,Li, Chun
-
supporting information
p. 415 - 419
(2022/01/12)
-
- Ferrocene derivative metal organic complex as well as preparation method and application thereof
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The invention relates to the technical field of organic synthesis, in particular to a ferrocene derivative metal organic complex and a preparation method and application thereof. The ferrocene derivative metal organic complex disclosed by the invention is shown I, contains a pincerlike ligand in the structure, and therefore has high stability and long service life. , The ferrocene derivative type metal organic complex has high catalytic activity, and only 0.001 μM % - 0.01 μM % is used, so that the chiral compound can be efficiently and rapidly prepared. The ferrocene derivative metal organic complex central metal is ruthenium, the economic cost is low, and the method has the prospect of industrial popularization.
- -
-
Paragraph 0147-0157
(2021/12/07)
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- Dynamic Kinetic Resolution of Alcohols by Enantioselective Silylation Enabled by Two Orthogonal Transition-Metal Catalysts
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A nonenzymatic dynamic kinetic resolution of acyclic and cyclic benzylic alcohols is reported. The approach merges rapid transition-metal-catalyzed alcohol racemization and enantioselective Cu-H-catalyzed dehydrogenative Si-O coupling of alcohols and hydrosilanes. The catalytic processes are orthogonal, and the racemization catalyst does not promote any background reactions such as the racemization of the silyl ether and its unselective formation. Often-used ruthenium half-sandwich complexes are not suitable but a bifunctional ruthenium pincer complex perfectly fulfills this purpose. By this, enantioselective silylation of racemic alcohol mixtures is achieved in high yields and with good levels of enantioselection.
- Oestreich, Martin,Seliger, Jan
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p. 247 - 251
(2020/10/29)
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- Ruthenium-catalyzed hydrogenation of aromatic ketones using chiral diamine and monodentate achiral phosphine ligands
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The Ru-catalyzed asymmetric hydrogenation of ketones with chiral diamine and monodentate achiral phosphine has been developed. A wide range of ketones were hydrogenated to afford the corresponding chiral secondary alcohols in good to excellent enantioselectivities (up to 98.1% ee). In addition, an appropriate mechanism for the asymmetric hydrogenation was proposed and verified by NMR spectroscopy.
- Wang, Mengna,Zhang, Ling,Sun, Hao,Chen, Qian,Jiang, Jian,Li, Linlin,Zhang, Lin,Li, Li,Li, Chun
-
-
- Abiotic reduction of ketones with silanes catalysed by carbonic anhydrase through an enzymatic zinc hydride
-
Enzymatic reactions through mononuclear metal hydrides are unknown in nature, despite the prevalence of such intermediates in the reactions of synthetic transition-metal catalysts. If metalloenzymes could react through abiotic intermediates like these, then the scope of enzyme-catalysed reactions would expand. Here we show that zinc-containing carbonic anhydrase enzymes catalyse hydride transfers from silanes to ketones with high enantioselectivity. We report mechanistic data providing strong evidence that the process involves a mononuclear zinc hydride. This work shows that abiotic silanes can act as reducing equivalents in an enzyme-catalysed process and that monomeric hydrides of electropositive metals, which are typically unstable in protic environments, can be catalytic intermediates in enzymatic processes. Overall, this work bridges a gap between the types of transformation in molecular catalysis and biocatalysis. [Figure not available: see fulltext.]
- Ji, Pengfei,Park, Jeeyoung,Gu, Yang,Clark, Douglas S.,Hartwig, John F.
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p. 312 - 318
(2021/02/26)
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- An Enantioconvergent Benzylic Hydroxylation Using a Chiral Aryl Iodide in a Dual Activation Mode
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The application of a triazole-substituted chiral iodoarene in a direct enantioselective hydroxylation of alkyl arenes is reported. This method allows the rapid synthesis of chiral benzyl alcohols in high yields and stereocontrol, despite its nontemplated nature. In a cascade activation consisting of an initial irradiation-induced radical C-H-bromination and a consecutive enantioconvergent hydroxylation, the iodoarene catalyst has a dual role. It initiates the radical bromination in its oxidized state through an in-situ-formed bromoiodane and in the second, Cu-catalyzed step, it acts as a chiral ligand. This work demonstrates the ability of a chiral aryl iodide catalyst acting both as an oxidant and as a chiral ligand in a highly enantioselective C-H-activating transformation. Furthermore, this concept presents an enantioconvergent hydroxylation with high selectivity using a synthetic catalyst.
- Abazid, Ayham H.,Clamor, Nils,Nachtsheim, Boris J.
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p. 8042 - 8048
(2020/09/21)
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- Chiral Imidazo[1,5- a]pyridine-Oxazolines: A Versatile Family of NHC Ligands for the Highly Enantioselective Hydrosilylation of Ketones
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Herein we report the synthesis and application of a versatile class of N-heterocyclic carbene ligands based on an imidazo[1,5-a]pyridine-3-ylidine backbone that is fused to a chiral oxazoline auxiliary. The key step in the synthesis of these ligands involves the installation of the oxazoline functionality via a microwave-assisted condensation of a cyano-azolium salt with a wide variety of 2-amino alcohols. The resulting chiral bidentate NHC-oxazoline ligands form stable complexes with rhodium(I) that are efficient catalysts for the enantioselective hydrosilylation of structurally diverse ketones. The corresponding secondary alcohols are isolated in good yields (typically >90%) with good to excellent enantioselectivities (80-93% ee). The reported hydrosilylation occurs at ambient temperatures (40 °C), with excellent functional group tolerability. Even ketones bearing heterocyclic substituents (e.g., pyridine or thiophene) or complex organic architectures are hydrosilylated efficiently, which is discussed further in this report.
- Chinna Ayya Swamy,Varenikov, Andrii,Ruiter, Graham De
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supporting information
p. 247 - 257
(2020/02/04)
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- Asymmetric transfer hydrogenation of ketones promoted by manganese(I) pre-catalysts supported by bidentate aminophosphines
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A series of commercially available chiral amino-phosphines, in combination with Mn(CO)5Br, has been evaluated for the asymmetric reduction of ketones, using isopropanol as hydrogen source. With the most selective ligand, the corresponding manga
- Azouzi, Karim,Bruneau-Voisine, Antoine,Vendier, Laure,Sortais, Jean-Baptiste,Bastin, Stéphanie
-
-
- A simple and efficient asymmetric hydrogenation of heteroaromatic ketones with iridium catalyst composed of chiral diamines and achiral phosphines
-
An efficient iridium catalyst composed of a simple and commercially available o-methoxytriphenylphosphine and 9-Amino (9-deoxy) epi-cinchonine was applied to the asymmetric hydrogenation of heteroaromatic ketones. A range of simple heteroaromatic ketones could be hydrogenated with good to excellent enantioselectivities and high activities. In particular, thiophene ketones and furyl ketones furnished 98.6% ee with up to 2.18 × 104(1/h) TOF. This catalytic system can be of practical value.
- Li, Chun,Lu, Xunhua,Wang, Mengna,Zhang, Ling,Jiang, Jian,Yan, Shunfa,Yang, Yuanyong,Zhao, Yonglong,Zhang, Lin
-
-
- Enhanced activity and modified substrate-favoritism of Burkholderia cepacia lipase by the treatment with a pyridinium alkyl-PEG sulfate ionic liquid
-
Three types of pyridinium salts, i.e., 1-ethylpyridin-1-ium cetyl-PEG10 sulfate (PYET), 1-butylpyridin-1-ium cetyl-PEG10 sulfate (PYBU), and 1-(3-methoxypropyl)pyridin-1-ium cetyl-PEG10 sulfate (PYMP), have been prepared and evaluated for their activation property of Burkholderia cepacia lipase by comparison to the control IL-coated enzymes, 1-butyl-2,3-dimethylimidazolium cetyl-PEG10 sulfate-coated lipase PS (IL1-PS). Among the tested pyridinium salt-coated lipases, the PYET-coated lipase PS (PYET-PS) exhibited the best results; the transesterification of 1-(pyridin-2-yl)ethanol, 1-(pyridin-3-yl)ethanol, 1-(pyridin-4-yl)ethanol, or 4-phenylbut-3-en-2-ol proceeded faster than those of the IL1-PS-catalyzed reaction while maintaining an excellent enantioselectivity (E > 200). This improved efficiency was found to be dependent on the increased Kcat value.
- Kadotani, Shiho,Nokami, Toshiki,Itoh, Toshiyuki
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p. 441 - 447
(2019/01/04)
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- Manganese Catalyzed Asymmetric Transfer Hydrogenation of Ketones Using Chiral Oxamide Ligands
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The asymmetric transfer hydrogenation of ketones using isopropyl alcohol (IPA) as hydrogen donor in the presence of novel manganese catalysts is explored. The selective and active systems are easily generated in situ from [MnBr(CO)5] and inexpensive C2-symmeric bisoxalamide ligands. Under the optimized reaction conditions, the Mn-derived catalyst gave higher enantioselectivity compared with the related ruthenium catalyst.
- Schneek?nig, Jacob,Junge, Kathrin,Beller, Matthias
-
supporting information
p. 503 - 507
(2019/02/26)
-
- Ruthenium(II)-Chitosan, an Enantioselective Catalyst for the Transfer Hydrogenation of N-Heterocyclic Ketones
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The present study aimed at extending the applicability of a recently developed stereoselective catalytic system to the preparation of optically enriched N-heterocyclic alcohols. Chiral ruthenium catalyst formed in situ using the chitosan biopolymer as ligand, which provided good results in the transfer hydrogenation of heterobicyclic compounds, such as 4-chromanone and 4-thiochromanone, was used in reactions of various N-containing prochiral ketones. High enantioselectivities were reached in transfer hydrogenations of bicyclic compounds bearing nitrogen either in aromatic or cycloaliphatic moieties, provided that the amino group was protected or shielded by a nearby substituent. Results were rationalized by interactions of the nitrogen with the metal and/or ligand. N-containing bicyclic compounds having heteroatoms in both rings were also prepared and tested. The detrimental effect of the pyridyl moiety was compensated by the beneficial influence of the heteroatom in the cycloaliphatic ring, as indicated by high rates and good enantioselectivities obtained in reactions of these compounds. Preparation of several N-heterocyclic alcohols, in good yields and high optical purities was achieved using Ru(II)-chitosan complex.
- Kolcsár, Vanessza Judit,Fül?p, Ferenc,Sz?ll?si, Gy?rgy
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p. 2725 - 2731
(2019/05/24)
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- Hydroclassified Combinatorial Saturation Mutagenesis: Reshaping Substrate Binding Pockets of KpADH for Enantioselective Reduction of Bulky-Bulky Ketones
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A hydroclassified combinatorial saturation mutagenesis (HCSM) strategy was proposed for reshaping the substrate binding pocket by dividing 20 amino acids into four groups based on their hydrophobicity and size. These smart HCSM libraries could significantly reduce screening effort especially for the simultaneous mutagenesis of three or more residues and lacking high throughput screening methods. Employing HCSM strategy, the stereoselectivity of KpADH, an alcohol dehydrogenase from Kluyveromyces polysporus, was efficiently improved to 99.4% ee. (4-Chlorophenyl)(pyridin-2-yl)methanone (CPMK), generally regarded as a "hard-to-reduce" ketone, was used as a model substrate, and its corresponding chiral alcohol products could be utilized as antihistamine precursors. The best variant 50C10 displayed higher binding affinity and catalytic efficiency toward CPMK with KM/kcat of 59.3 s-1·mM-1, 3.51-fold that of KpADH. Based on MD simulations, increased difference between two binding pockets, enhanced hydrophobicity, and π-π and halogen-alkyl interactions were proposed to favor the enantioselective recognition and substrate binding in 50C10. Substrate spectrum analysis revealed that 50C10 exhibited improved enantioselectivity toward diaryl ketones especially with halo- or other electron-withdrawing groups. As much as 500 mM CPMK could be asymmetrically reduced into chiral diaryl alcohols with ee of 99.4% and a space-time yield of 194 g·L-1·d-1 without addition of external NADP+. This study provides an effective mutagenesis strategy for the protein engineering of substrate specificity and enantioselectivity.
- Xu, Guo-Chao,Wang, Yue,Tang, Ming-Hui,Zhou, Jie-Yu,Zhao, Jing,Han, Rui-Zhi,Ni, Ye
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p. 8336 - 8345
(2018/09/18)
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- Remarkably improved stability and enhanced activity of a: Burkholderia cepacia lipase by coating with a triazolium alkyl-PEG sulfate ionic liquid
-
Three types of triazolium cetyl-PEG10 sulfate ionic liquid were synthesized and their activation of Burkholderia cepacia lipase was investigated; both the reaction rate and enantioselectivity depended on the cationic part of the coating ILs and 1-butyl-3-methyl-1,2,3-triazolium cetyl-PEG10 sulfate (Tz1)-coated lipase PS, which is especially suitable for the transesterification of 1-(pyridin-2-yl)ethanol, 1-(pyridin-3-yl)ethanol, and 1-(pyridin-4-yl)ethanol, among 12 types of tested secondary alcohol. The most important result was obtained when these enzymes were stored in an IL ([N221MEM][Tf2N]) solvent: Tz1-PS showed an amazing stability and it exhibited an excellent activity after 2 years when the enzyme was stored in [N221MEM][Tf2N].
- Nishihara,Shiomi,Kadotani,Nokami,Itoh
-
supporting information
p. 5250 - 5256
(2017/11/09)
-
- One-pot synthesis of (R)-1-(pyridin-4-yl)ethyl acetate using tandem catalyst prepared by co-immobilization of palladium and lipase on mesoporous foam: Optimization and kinetic modeling
-
The synthesis of (R)-1-(pyridin-4-yl)ethyl acetate was achieved over tandem palladium-lipase catalyst with 100% selectivity using 4-acetyl pyridine as a reactant. The 2% w/w palladium and lipase catalyst was successfully co-immobilized in the microenvironment of the mesocellular foam and characterized by various techniques. The palladium metal from catalyst hydrogenated 4-acetyl pyridine to form 1-(pyridin-4-yl)ethanol. The generated intermediate product then underwent kinetic resolution over lipase and selectively gave (R)-1-(pyridin-4- yl)ethyl acetate. The catalytic conditions were then studied for optimal performance of both steps. The reaction conditions were optimized to 50?°C and toluene as a solvent. Both chemical and enzymatic kinetic models of the reaction were developed for a given set of reaction conditions and kinetic parameters were predicted. At optimal conditions, the obtained selectivity of intermediate (1-(pyridin-4-yl)ethanol) was 51.38%. The final product yield of ((R)-1-(pyridin-4-yl)ethyl acetate) was 48.62%.
- Magadum, Deepali B.,Yadav, Ganapati D.
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p. 811 - 823
(2017/10/09)
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- Mechanochemical Enzymatic Kinetic Resolution of Secondary Alcohols under Ball-Milling Conditions
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Mechanosynthesis is a valuable technique, offering attractive alternatives for the preparation of organic, inorganic, and organometallic products. Surprisingly, mechanochemical enzymatic transformations have only scarcely been studied until now. Here, we demonstrate the use of lipase B from Candida antarctica (CALB) in acylative kinetic resolutions of secondary alcohols in mixer and planetary mills. Despite the mechanical stress caused by the high-speed ball milling, the biocatalyst proved highly effective, stable, and, in part, recyclable under the applied mechanochemical conditions. Best milling practice: The compatibility of lipase B from Candida antarctica (CALB) in acylative kinetic resolutions of secondary alcohols in mixer and planetary mills has been explored. Despite the mechanical stress caused by the high-speed ball milling, the biocatalyst was found to be very effective, stable, and, in part, recyclable under the applied mechanochemical conditions.
- Hernández, José G.,Frings, Marcus,Bolm, Carsten
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p. 1769 - 1772
(2016/06/01)
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- Third-Generation Amino Acid Furanoside-Based Ligands from d-Mannose for the Asymmetric Transfer Hydrogenation of Ketones: Catalysts with an Exceptionally Wide Substrate Scope
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A modular ligand library of α-amino acid hydroxyamides and thioamides was prepared from 10 different N-tert-butyloxycarbonyl-protected α-amino acids and three different amino alcohols derived from 2,3-O-isopropylidene-α-d-mannofuranoside. The ligand library was evaluated in the half-sandwich ruthenium- and rhodium-catalyzed asymmetric transfer hydrogenation of a wide array of ketone substrates, including simple as well as sterically demanding aryl alkyl ketones, aryl fluoroalkyl ketones, heteroaromatic alkyl ketones, aliphatic, conjugated and propargylic ketones. Under the optimized reaction conditions, secondary alcohols were obtained in high yields and in enantioselectivities up to >99%. The choice of ligand/catalyst allowed for the generation of both enantiomers of the secondary alcohols, where the ruthenium-hydroxyamide and the rhodium-thioamide catalysts act complementarily towards each other. The catalytic systems were also evaluated in the tandem isomerization/asymmetric transfer hydrogenation of racemic allylic alcohols to yield enantiomerically enriched saturated secondary alcohols in up to 98% ee. Furthermore, the catalytic tandem α-alkylation/asymmetric transfer hydrogenation of acetophenones and 3-acetylpyridine with primary alcohols as alkylating and reducing agents was studied. Secondary alcohols containing an elongated alkyl chain were obtained in up to 92% ee. (Figure presented.).
- Margalef, Jèssica,Slagbrand, Tove,Tinnis, Fredrik,Adolfsson, Hans,Diéguez, Montserrat,Pàmies, Oscar
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p. 4006 - 4018
(2016/12/30)
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- Synthesis of enantiopure epoxide by 'one pot' chemoenzymatic approach using a highly enantioselective dehydrogenase
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Enantiopure α-phenethyl alcohols, including aromatic halohydrins, are important chiral building blocks. One of the best approaches to synthesise α-phenethyl alcohols is asymmetric reduction of prochiral ketones by alcohol dehydrogenases (ADHs). The obtained enantiopure halohydrin could be directly used to produce enantiopure epoxide through a base-induced ring-closure reaction, which is an attractive 'one pot' chemoenzymatic method for producing high-yield epoxide. In this study, a novel medium-chain dehydrogenase (KcDH) from Kuraishia capsulate CBS1993 was identified and characterised to show its broad substrate scope and excellent enantioselectivity. KcDH showed activities on 25 substrates of the 26 tested aromatic ketones and heteroaryl ketones, with an enantiomeric excess (ee) >99% and the highest relative activity observed with para-nitro acetophenone. Due to its high enantioselectivity for α-haloketones, a chemoenzymatic method for the synthesis of enantiopure styrene oxide (SO) and phenyl glycidyl ether (PGE) was developed through a base-induced ring-closure reaction on enantiopure halohydrin obtained with KcDH. (R)-SO and (S)-PGE were obtained in 86% and 94% analytical yield, respectively, and both epoxides were obtained with ee >99%. Thus, our results suggested that KcDH may be a promising biocatalyst for the production of multiple enantiopure α-phenethyl alcohols and epoxides.
- Wu, Kai,Chen, Lifeng,Fan, Haiyang,Zhao, Zhiqiang,Wang, Hualei,Wei, Dongzhi
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p. 899 - 904
(2016/02/05)
-
- Development of Large-Scale Routes to Potent GPR119 Receptor Agonists
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Practical and scalable syntheses were developed that were used to prepare multikilogram batches of GSK1292263A (1) and GSK2041706A (15), two potent G protein-coupled receptor 119 (GPR119) agonists. Both syntheses employed relatively cheap and readily avai
- Matsuoka, Richard T.,Boros, Eric E.,Brown, Andrew D.,Bullock, Kae M.,Canoy, Will L.,Carpenter, Andrew J.,Cobb, Jeremy D.,Condon, Shannon E.,Deschamps, Nicole M.,Elitzin, Vassil I.,Erickson, Greg,Fang, Jing M.,Igo, David H.,Joshi, Biren K.,Kaldor, Istvan W.,Mitchell, Mark B.,Peckham, Gregory E.,Reynolds, Daniel W.,Salmon, Matthew C.,Sharp, Matthew J.,Tabet, Elie A.,Toczko, Jennifer F.,Wu, Lianming Michael,Zhou, Xiao-Ming M.
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p. 1469 - 1475
(2016/08/30)
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- Kinetic resolution of secondary alcohols with Burkholderia cepacia lipase immobilized on a biodegradable ternary blend polymer matrix as a highly efficient and heterogeneous recyclable biocatalyst
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The present work reports a highly efficient and biocatalytic heterogeneous protocol for kinetic resolution (KR) of racemic secondary alcohols with vinyl acetate as an acyl donor, using the biocatalyst Burkholderia cepacia lipase (BCL) immobilized on a biodegradable ternary blend support through polylactic acid (PLA)/polyvinyl alcohol (PVA)/chitosan (CHI); (PLA/PVA/CHI-BCL). The KR reaction with various substituted aromatic, heterocyclic racemic secondary alcohols gave enantiomerically pure alcohol and its enantioenriched acetate derivatives with high conversion (45-50%) and excellent enantiomeric excess (up to 99% ee) at optimized reaction conditions. The reaction works under mild conditions using simple and inexpensive starting materials such as racemic alcohols, vinyl acetate, and immobilized biocatalyst. The given protocol provides excellent recyclability with good yield and enantiomeric excess values up to the studied range of five cycles. The resultant products were characterized with the help of different analytical techniques such as 1H and 13C-NMR, chiral HPLC column, polarimeter, IR and GC-MS.
- More, Ganesh V.,Badgujar, Kirtikumar C.,Bhanage, Bhalchandra M.
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p. 4592 - 4598
(2015/02/19)
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- Heterogeneous asymmetric hydrogenation of heteroaromatic methyl ketones catalyzed by cinchona-modified iridium catalysts
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A heterogeneous iridium catalyst was synthesized with silica particles as support for the hydrogenation of heteroaromatic methyl ketones. The catalyst and support were characterized by solid-state NMR, HTEM, SEM, XPS, and BET. A series of heteroaromatic methyl ketones were investigated at room temperature. The catalytic system was effective and more than 99% conversion and up to 83.6% enantioselectivity were obtained in the hydrogenation of heteroaromatic methyl ketones.
- Li, Chun,Zhang, Lin,Zheng, Congye,Zheng, Xueli,Fu, Haiyan,Chen, Hua,Li, Ruixiang
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p. 821 - 824
(2014/06/23)
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- Modular hydroxyamide and thioamide pyranoside-based ligand library from the sugar pool: New class of ligands for asymmetric transfer hydrogenation of ketones
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A large library of pyranoside-based hydroxyamide and thioamide ligands has been synthesized for asymmetric transfer hydrogenation in an attempt to expand the scope of the substrates to cover a broader range of challenging heteroaromatic and aryl/fluoroalkyl ketones. These ligands have the advantage that they are prepared from commercial D-glucose, D-glucosamine and α-amino acids, inexpensive natural chiral feedstocks. By carefully selecting the ligand components (substituents/configurations at the amide/thioamide moiety, the position of amide/thioamide group and the configuration at C-2), we found that pyranoside-based thioamide ligands provided excellent enantioselectivities (in the best cases, ees of >99% were achieved) in a broad range of ketones, including the less studied heteroaromatics and challenging aryl/fluoroalkyls. Note that both enantiomers of the reduction products can be obtained with excellent enantioselectivities by simply changing the absolute configuration of the thioamide substituent.
- Coll, Mercè,Pàmies, Oscar,Diéguez, Montserrat
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p. 2293 - 2302
(2014/07/21)
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- Highly enantioselective transfer hydrogenation of ketones with chiral (NH)2P2 Macrocyclic Iron(II) complexes
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Bis(isonitrile) iron(II) complexes bearing a C2-symmetric diamino (NH)2P2 macrocyclic ligand efficiently catalyze the hydrogenation of polar bonds of a broad scope of substrates (ketones, enones, and imines) in high yield (up to 99.5 %), excellent enantioselectivity (up to 99 % ee), and with low catalyst loading (generally 0.1 mol %). The catalyst can be easily tuned by modifying the substituents of the isonitrile ligand. Paying the iron price: Bis(isonitrile) iron(II) complexes with a C2-symmetric diamino (NH)2P2 macrocyclic ligand efficiently catalyze the hydrogenation of polar bonds of a broad scope of substrates (ketones, enones, imines) in high yield (up to 99.5 %), excellent enantioselectivity (up to 99 % ee), and with low catalyst loading (generally 0.1 mol %).
- Bigler, Raphael,Huber, Raffael,Mezzetti, Antonio
-
supporting information
p. 5171 - 5174
(2015/04/27)
-
- Iron catalyzed asymmetric hydrogenation of ketones
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Chiral molecules, such as alcohols, are vital for the manufacturing of fine chemicals, pharmaceuticals, agrochemicals, fragrances, and novel materials. These molecules need to be produced in high yield and high optical purity and preferentially catalytically. Among all the asymmetric catalytic reactions, asymmetric hydrogenation with H2 (AH) is the most widely used in the industry. With few exceptions, these AH processes use catalysts based on the three critical metals, rhodium, ruthenium, and iridium. Herein we describe a simple, industrially viable iron catalyst that allows for the AH of ketones, a process currently dominated by ruthenium and rhodium catalysts. By combining a chiral, 22-membered macrocyclic ligand with the cheap, readily available Fe 3(CO)12, a wide variety of ketones have been hydrogenated under 50 bar H2 at 45-65 C, affording highly valuable chiral alcohols with enantioselectivities approaching or surpassing those obtained with the noble metal catalysts. In contrast to AH by most noble metal catalysts, the iron-catalyzed hydrogenation appears to be heterogeneous.
- Li, Yanyun,Yu, Shenluan,Wu, Xiaofeng,Xiao, Jianliang,Shen, Weiyi,Dong, Zhenrong,Gao, Jingxing
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supporting information
p. 4031 - 4039
(2014/04/03)
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- Practical synthesis of optically active alcohols via asymmetric transfer hydrogenation of aromatic ketones using chiral Rh(III)-monosulfonamide ligand complex in aqueous media
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A series of monosulfonamide derivatives were synthesized and tested as chiral ligands in the Ru(II),Rh(III)-catalyzed transfer hydrogenation of aromatic ketones in aqueous sodium formate and isopropanol/potassium hydroxide. Possible secondary Cp*methyl- s
- Cortez, Norma A.,Aguirre, Gerardo,Parra-Hake, Miguel,Somanathan, Ratnasamy,Arita, Amy J.,Cooksy, Andrew L.,De Parrodi, Cecilia Anaya,Huelgas, Gabriela
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experimental part
p. 73 - 84
(2011/03/19)
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- Efficient reduction of ethyl 2-oxo-4-phenylbutyrate at 620 ?l -1 by a bacterial reductase with broad substrate spectrum
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A β-ketoacyl-ACP reductase (FabG) gene from Bacillus sp. ECU0013 was heterologously overexpressed in Escherichia coli and the encoded protein was purified to homogeneity. The recombinant reductase could reduce a broad spectrum of prochiral ketones including aromatic ketones and keto esters and showed the highest activity in the asymmetric reduction of ethyl 2-oxo-4-phenylbutyrate (OPBE). Using E. coli cells coexpressing both FabG and glucose dehydrogenase (GDH) genes, as much as 620 ?L-1 of OPBE was almost stoichiometrically converted to ethyl (S)-2-hydroxy-4-phenylbutyrate [(S)-HPBE] with excellent (>99%) enantiomeric excess. More importantly, the process could be performed smoothly without external addition of an expensive cofactor as usually done and could be scaled up very easily. All these positive features demonstrate the applicability of this reductase for the large-scale production of optically active α-hydroxy acids/esters.
- Ni, Yan,Li, Chun-Xiu,Zhang, Jie,Shen, Nai-Dong,Bornscheuer, Uwe T.,Xu, Jian-He
-
supporting information; experimental part
p. 1213 - 1217
(2011/07/09)
-
- Copper-dipyridylphosphine-polymethylhydrosiloxane: A practical and effective system for the asymmetric catalytic hydrosilylation of ketones
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In the presence of the inexpensive and non-toxic stoichiometric reductant polymethylhydrosiloxane (PMHS), the chiral copper(II)-dipyridylphosphine catalyst displayed high efficiency in the stereoselective hydrosilylation of a wide scope of aryl alkyl and heteroaromatic ketones under an air atmosphere and mild conditions in good to excellent ees (up to 97%). With certain amounts of sodium tert-butoxide and tert-butyl alcohol as additives, the reaction on a 21-g substrate scale can be conveniently completed within a few hours even at a substrate-to-ligand (S/L) ratio of 50,000. Copyright
- Zhang, Xi-Chang,Wu, Fei-Fei,Li, Shijun,Zhou, Ji-Ning,Wu, Jing,Li, Ning,Fang, Wenjun,Lam, Kim Hung,Chan, Albert S. C.
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supporting information; experimental part
p. 1457 - 1462
(2011/08/03)
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- Highly stereoselective reduction of prochiral ketones by a bacterial reductase coupled with cofactor regeneration
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A carbonyl reductase gene (yueD) from Bacillus sp. ECU0013 was heterologously overexpressed in Escherichia coli, and the encoded protein (BYueD) was purified to homogeneity and characterized. The NADPH-dependent reductase showed a broad substrate spectrum towards different aromatic ketones, and α- and β-ketoesters. Although the enantioselectivity was high to moderate for the reduction of α-ketoesters, all the tested β-ketoesters and aromatic ketones were reduced to the corresponding chiral alcohols in enantiomerically pure forms. Furthermore, the practical applicability of this enzyme was evaluated for the reduction of ethyl 4-chloro-3-oxobutanoate (1a). Using Escherichia coli cells coexpressing BYueD and glucose dehydrogenase, 215 g L-1 (1.3 M) of 1a was stoichiometrically converted to ethyl (R)-4-chloro-3-hydroxybutanoate ((R)-1b) in an aqueous-toluene biphasic system by using a substrate fed-batch strategy, resulting in an overall hydroxyl product yield of 91.7% with enantiomeric purity of 99.6% ee.
- Ni, Yan,Li, Chun-Xiu,Wang, Li-Juan,Zhang, Jie,Xu, Jian-He
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experimental part
p. 5463 - 5468
(2011/09/12)
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- Chemo-and stereoselective iron-catalyzed hydrosilylation of ketones
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The reduction of ketones with polymethylhydrosiloxane (PMHS) gives the corresponding alcohols in good to excellent yield applying iron-based catalyst systems. In the case of prochiral ketones, the use of Fe(OAc) 2/(S,S)-Me-DuPhos leads to high enantioselectivity up to 99% ee. The reaction proceeds in the presence of several functional groups such as esters, halides as well as conjugated double bonds, with high chemoselectivity. The advantage of this protocol is that the reaction requires no activating agents or additives.
- Addis, Daniele,Shaikh, Nadim,Zhou, Shaolin,Das, Shoubhik,Junge, Kathrin,Beller, Matthius
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experimental part
p. 1687 - 1691
(2011/08/05)
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- BICYCLIC COMPOUNDS AND USE AS ANTIDIABETICS
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The present invention relates to novel compounds that are useful in the treatment of metabolic disorders, particularly type II diabetes mellitus and related disorders, and also to the methods for the making and use of such compounds.
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Page/Page column 75
(2010/03/02)
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- Iron(ii)-bis(isonitrile) complexes: Novel catalysts in asymmetric transfer hydrogenations of aromatic and heteroaromatic ketones
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Chiral iron(ii)-bis(isonitrile) complexes catalyse the transfer hydrogenation of aromatic ketones with enantioselectivities up to 91% ee, most likely via hydride transfer through imine intermediates, generated by in situ reduction of the isonitrile ligands, whereas iron acts as a Lewis acid to activate the ketone.
- Naik, Anu,Maji, Tapan,Reiser, Oliver
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supporting information; experimental part
p. 4475 - 4477
(2010/11/03)
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- Synthesis of chiral aromatic alcohols: Use of new C2-symmetric RhIIICp*, RuII(cymene), or RuII(benzene) complexes containing chiral diaminocyclohexane ligand as asymmetric transfer hydrogenation catalyst
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Twelve chiral secondary alcohols were synthesized by asymmetric transfer hydrogenation (ATH) using C2-symmetric bis(sulfonamide) ligand (2) derived from (1R,2R)-cyclohexane-1,2-diamine and complexed with [RhCl 2CP*]2, [RuCl2(cymene)] 2, or [RuCl2(benzene)]2 and then used in situ in the reduction of prochiral ketones. The alcohols were obtained in 85-99% yield and 90-99% enantioselectivity with isopropanol as the hydrogen source. Two-fold rate enhancement and better yields were achieved (88-99%) with 80-99% enantioselectivity using the complex [RhCl2CP*] 2 and aqueous sodium formate as the hydrogen source.
- Montalvo-Gonzalez, Ruben,Chavez, Daniel,Aguirre, Gerardo,Parra-Hake, Miguel,Somanathan, Ratnasamy
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experimental part
p. 2737 - 2746
(2009/12/06)
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- Highly enantioselective synthesis of heteroaromatic alcohols catalyzed by chiral diaminodiphosphine-ruthenium(II) complexes
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Chiral diaminodiphosphine-ruthenium(II) complexes were found to be excellent catalysts for the asymmetric transfer hydrogenation of heteroaromatic ketones in propan-2-ol. In the presence of potassium hydroxide, the enantioselective reduction of heteroaromatic ketones proceeded smoothly to give chiral alcohols with excellent enantiomeric excess (up to 97% ee) under mild conditions without reduction of the heterocycle. Georg Thieme Verlag Stuttgart.
- Shen, Wei-Yi,Li, Yan-Yun,Dong, Zhen-Rong,Gao, Jing-Xing
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experimental part
p. 2413 - 2417
(2010/01/19)
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- Application of copper(II)-dipyridylphosphine catalyst in the asymmetric hydrosilylation of simple ketones in air
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Copper (II)-dipyridylphosphine catalyst was used in the asymmetric hydrosilylation of simple ketones under ambient conditions in competitive levels of enantioinduction and activity. The experiment also described the utility of the combination of copper(II) salt/(S)-1/PhSiH3 in the enantioselective hydrosilylation of heteroaromatic ketones and several other ketonic substrates leading to some valuable pharmaceutical and agricultural chemical intermediates. A number of the resulting chiral alcohols represented valuable intermediates for some physiologically active compounds, with remarkable temperature effects on the asymmetric induction were observed in some cases of heteroaromatic ketones. The results show that the present catalyst system features widespread substrate scope, high air stability, fast rate of reaction, good-to-excellent enantioselectivity, and mild conditions thereby affording a practical protocol to a vast selection of optically enriched alcohols.
- Zhang, Xi-Chang,Wu, Yan,Yu, Feng,Wu, Fei-Fei,Wu, Jing,Chan, Albert S. C.
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supporting information; experimental part
p. 5888 - 5891
(2010/03/03)
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- Highly enantioselective carbonyl reduction with borane catalyzed by chiral spiroborate esters derived from chiral beta-aminoalcohols
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Novel spiroborate esters derived from non-recemic 1,2-amino alcohols were examined as chiral catalyst in the borane reduction of acetophenone and other aromatic ketones at room temperature. The optically active alcohols were obtained in excellent chemical yields and up to 99% ee with less than 10% catalyst.
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Page/Page column 2
(2008/12/08)
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- Hydrogen transfer reduction of different ketones in ionic liquids
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Ionic liquids were tested as the reaction media for hydrogen transfer reduction of substituted acetophenones and some other ketones with the [RuCl(TsDPEN)]2 complex as the catalyst. Reactions were going well and faster than in common solvents. Corresponding alcohols had high ees in the case of aryl alkyl ketones, but just medium ees were reached in the case of dialkyl or unsaturated ketones. An interesting phenomenon was observed, namely that rise of the reaction temperature did not have negative influence on the ee of the reaction product.
- Hut'ka, Martin,Toma, Stefan
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experimental part
p. 793 - 798
(2009/09/29)
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- Novel fluorous prolinol as a pre-catalyst for catalytic asymmetric borane reduction of various ketones
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Novel prolinol carrying two perfluorohexylethyl groups at the α-position was prepared from l-proline as a starting chiral substrate. Catalytic asymmetric reduction of various ketones, including mono-, di-, and trifluoromethylated acetophenones, using fluo
- Goushi, Sakiko,Funabiki, Kazumasa,Ohta, Masaya,Hatano, Keisuke,Matsui, Masaki
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p. 4061 - 4066
(2007/12/30)
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- Water-soluble chiral monosulfonamide-cyclohexane-1,2-diamine-RhCp* complex and its application in the asymmetric transfer hydrogenation (ATH) of ketones
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Monosulfonamide ligands with heteroatom/heterocyclic systems were derived from trans-(1R,2R)-cyclohexane-1,2-diamine and complexed with [Ru(benzene)Cl2]2, [Cp*RhCl2]2 in situ and used in the ATH of ar
- Cortez, Norma A.,Aguirre, Gerardo,Parra-Hake, Miguel,Somanathan, Ratnasamy
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p. 4335 - 4338
(2008/02/08)
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- Increased enantioselectivity and remarkable acceleration of lipase-catalyzed transesterification by using an imidazolium PEG-Alkyl sulfate ionic liquid
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Several types of imidazolium salt ionic liquids were prepared derived from poly(oxyethylene)alkyl sulfate and used as an additive or coating material for lipase-catalyzed transesterification in an organic solvent. A remarkably increased enantioselectivity was obtained when the salt was added at 3-10 mol % versus substrate in the Burkholderia cepacia lipase (lipase PS-C)-catalyzed transesterification of 1-phe nylethanol by using vinyl acetate in diisopropyl ether or a hexane solvent system. In particular, a remarkable acceleration was accomplished by the ionic liquid coating with lipase PS in an iPr2O solvent system while maintaining excellent enantioselectivity; it reached approximately 500- to 1000-fold acceleration for some substrates with excellent enantioselectivity. A similar acceleration was also observed for IL1-coated Candida rugosa lipase. MALDITOF mass spectrometry experiments of the ionic-liquid-coated lipase PS suggest that ionic liquid binds with lipase protein.
- Itoh, Toshiyuki,Matsushita, Yuichi,Abe, Yoshikazu,Han, Shi-Hui,Wada, Shohei,Hayase, Shuichi,Kawatsura, Motoi,Takai, Shigeomi,Morimoto, Minoru,Hirose, Yoshihiko
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p. 9228 - 9237
(2007/10/03)
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- Asymmetric reduction of ketones by employing Rhodotorula sp. AS2.2241 and synthesis of the β-blocker (R)-nifenalol
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A broad range of prochiral ketones were efficiently reduced to the corresponding optically active secondary alcohols using resting cells of Rhodotorula sp. AS2.2241. The microbial reduction system exhibited high activity and enantioselectivity in the reduction of various aromatic ketones and acetylpyridines (>97% ee), but moderate to high enantioselectivity in the reduction of α- and β-keto esters. (R)-Nifenalol, a β-adrenergic blocker, was also synthesized using 2-bromo-1(R)-(4-nitrophenyl)ethanol (97% ee) which was prepared through the asymmetric reduction of 2-bromo-1-(4-nitrophenyl)ethanone employing Rhodotorula sp. AS2.2241. The simple preparation and the high activity of the biocatalyst turned this system into a versatile tool for organic synthesis.
- Yang, Wei,Xu, Jian-He,Xie, Yan,Xu, Yi,Zhao, Gang,Lin, Guo-Qiang
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p. 1769 - 1774
(2007/10/03)
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- New C2-symmetric bis(sulfonamide)-cyclohexane-1,2-diamine-RhCp* complex and its application in the asymmetric transfer hydrogenation (ATH) of ketones in water
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C2-symmetric bis(sulfonamide) ligands derived from trans-(1R,2R)-cyclohexane-1,2-diamine were synthesized and complexed with [Cp*RhCl2]2 in situ and used in the ATH of aromatic ketones with aqueous sodium format
- Cortez, Norma A.,Rodríguez-Apodaca, Ramón,Aguirre, Gerardo,Parra-Hake, Miguel,Cole, Thomas,Somanathan, Ratnasamy
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p. 8515 - 8518
(2007/10/03)
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- The "reverse-tethered" ruthenium (II) catalyst for asymmetric transfer hydrogenation: Further applications
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The attachment of a tethering group from the basic nitrogen atom to the arene ligand of a ruthenium(II) catalyst greatly improves its ability to catalyze asymmetric transfer hydrogenation (ATH) reactions. In this paper, we describe further applications of this versatile system to an extended substrate range.
- Morris, David J.,Hayes, Aidan M.,Wills, Martin
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p. 7035 - 7044
(2007/10/03)
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- An outstanding catalyst for asymmetric transfer hydrogenation in aqueous solution and formic acid/triethylamine
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A Rh/tetramethylcyclopentadienyl complex containing a tethered functionality has been demonstrated to give excellent results in the asymmetric transfer hydrogenation of ketones in both aqueous and formic acid/triethylamine media. The Royal Society of Chemistry 2006.
- Matharu, Daljit S.,Morris, David J.,Clarkson, Guy J.,Wills, Martin
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p. 3232 - 3234
(2008/09/18)
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- Asymmetric transesterification of secondary alcohols catalyzed by feruloyl esterase from Humicola insolens
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A new asymmetric transesterification of secondary alcohols catalyzed by feruloyl esterase from Humicola insolens has been found. Although alcohols are not the natural substrates for this enzyme, a high R enantioselectivity was observed. Stereochemical studies showed that variations in substrate structure lead to strong variations in enantioselectivity. The highest enantioselectivities are obtained when the β-carbon of the secondary alcohol is tertiary or quaternary.
- Hatzakis, Nikos S.,Smonou, Ioulia
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p. 325 - 337
(2007/10/03)
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- How substrate solvation contributes to the enantioselectivity of subtilisin toward secondary alcohols
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The current rule to predict the enantiopreference of subtilisin toward secondary alcohols is based on the size of the substituents at the stereocenter and implies that the active site contains two differently sized pockets for these substituents. Several experiments are inconsistent with the current rule. First, the X-ray structures of subtilisin show there is only one pocket (the S1- pocket) approximately the size of a phenyl group to bind secondary alcohols. Second, the rule often predicts the incorrect enantiomer for reactions in water. To resolve these contradictions, we refine the current rule to show that subtilisin binds only one substituent of a secondary alcohol and leaves the other in solvent. To test this refined empirical rule, we show that the enantioselectivity of a series of secondary alcohols in water varied linearly with the difference in hydrophobicity (log P/P0) of the substituents. This hydrophobicity difference accounts for the solvation of one substituent in water. Copyright
- Savile, Christopher K.,Kazlauskas, Romas J.
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p. 12228 - 12229
(2007/10/03)
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- Combined ruthenium(II) and lipase catalysis for efficient dynamic kinetic resolution of secondary alcohols. Insight into the racemization mechanism
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Pentaphenylcyclopentadienyl ruthenium complexes (3) are excellent catalysts for the racemization of secondary alcohols at ambient temperature. The combination of this process with enzymatic resolution of the alcohols results in a highly efficient synthesis of enantiomerically pure acetates at room temperature with short reaction times for most substrates. This new reaction was applied to a wide range of functionalized alcohols including heteroaromatic alcohols, and for many of the latter, enantiopure acetates were efficiently prepared for the first time via dynamic kinetic resolution (DKR). Different substituted cyclopentadienyl ruthenium complexes were prepared and studied as catalysts for racemization of alcohols. Pentaaryl-substituted cyclopentadienyl complexes were found to be highly efficient catalysts for the racemization. Substitution of one of the aryl groups by an alkyl group considerably slows down the racemization process. A study of the racemization of (S)-1-phenylethanol catalyzed by ruthenium hydride η5-Ph5CpRu(CO) 2H (8) indicates that the racemization takes place within the coordination sphere of the ruthenium catalyst. This conclusion was supported by the lack of ketone exchange in the racemization of (S)-1-phenylethanol performed in the presence of p-tolyl methyl ketone (1 equiv), which gave 1% of 1-(p-tolyl)ethanol. The structures of ruthenium chloride and iodide complexes 3a and 3c and of ruthenium hydride complex 8 were confirmed by X-ray analysis.
- Martin-Matute, Belen,Edin, Michaela,Bogar, Krisztian,Kaynak, F. Betuel,Baeckvall, Jan-E.
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p. 8817 - 8825
(2007/10/03)
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- Ruthenium(II) complexes of monodonor ligands: Efficient reagents for asymmetric ketone hydrogenation
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A series of BINOL-derived ligands have been prepared and incorporated into ruthenium(II) complexes containing a diamine ligand. The complexes have proven to be excellent catalysts for the asymmetric hydrogenation of ketones, giving reduction products with enantiomeric excesses of up to 99%.
- Xu, Yingjian,Clarkson, Guy C.,Docherty, Gordon,North, Carl L.,Woodward, Gary,Wills, Martin
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p. 8079 - 8087
(2007/10/03)
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- Simple biocatalytic access to enantiopure (S)-1-heteroarylethanols employing a microbial hydrogen transfer reaction
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Lyophilised cells of various Rhodococcus spp. were employed in an efficient hydrogen transfer-like process for the asymmetric bioreduction of heteroaryl methyl ketones using 2-propanol as hydrogen donor. Besides the genus Rhodococcus, only Mycoplana rubra R14 showed a comparable stability towards elevated concentrations of the co-substrate 2-propanol. Among the organisms tested, Rhodococcus ruber DSM 44541 and DSM 43338 showed best activity and selectivity. With these strains, the reaction proceeded with high stereoselectivity (ee >99%) and predictable stereochemical outcome regardless of the nature of the heteroaromatic ring system. The reaction could be performed at the exceptional substrate concentration of up to 0.4 mol L -1 in an environmentally friendly aqueous-organic solvent mixture at room temperature and is easy to handle, thus providing a very practical tool to access enantio-pure 1-heteroarylethanols.
- Stampfer, Wolfgang,Edegger, Klaus,Kosjek, Birgit,Faber, Kurt,Kroutil, Wolfgang
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- Origin of enantioselectivity in the Ru(arene)(amino alcohol)-catalyzed transfer hydrogenation of ketones
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The origin of the enantioselectivity in the ruthenium-catalyzed transfer hydrogenation has been studied by means of experiment and density functional theory calculations. The results clearly show that electrostatic effects are of importance, not only in the T-shaped arene-aryl interaction in the favored transition state but also between the aryl of the substrate and the amine ligand in the disfavored TS. In addition, the electrostatic interaction between the alkyl substituent of the substrate and the catalyst is of importance to the enantioselectivity. The major cause of enantioselection is found to be of nonelectrostatic origin. This inherent property of the catalytic system is discussed in terms of dispersion forces and solvent effects. Finally, a minor but well-characterized steric effect was identified. The success of this class of catalysts in the reduction of alkyl aryl ketones is based on the fact that all factors work in the same direction.
- Brandt, Peter,Roth, Peter,Andersson, Pher G.
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p. 4885 - 4890
(2007/10/03)
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- Chiral [RuCl2(dipyridylphosphane)(1,2-diamine)] catalysts: Applications in asymmetric hydrogenation of a wide range of simple ketones
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The dipyridylphosphane/diamine - Ru complex combined with tBuOK in 2-propanol acts as a very effective catalyst system for the enantioselective hydrogenation of a diverse range of simple ketones including heteroaromatic ketones, substituted benzophenones, alkenyl ketones, and cyclopropyl ketones. The combination of desirable features, such as quantitative chemical yields within hours, broad substrate scope, excellent enantioselectivities (up to 99%), and high substrate-to-catalyst ratios, among others, makes the present catalyst system of high practical interest.
- Wu, Jing,Ji, Jian-Xin,Guo, Rongwei,Yeung, Chi-Hung,Chan, Albert S. C.
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p. 2963 - 2968
(2007/10/03)
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