- Ultrasound-promoted lipase-catalyzed reactions
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Lipase from porcine pancreas is first demonstrated to catalyze reactions under ultrasonic condition. Reaction rates are significantly enhanced 7 to 83-fold and enantioselectivities are retained.
- Lin, Gialih,Liu, Hsiao-Chien
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- Engineering a Carbonyl Reductase as a Potential Tool for the Synthesis of Chiral α-Tetralinols
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Tailoring of enzyme toward α-tetralones, a class of bulky-bulky ketones, is still a challenge. In this work, the mutants of carbonyl reductase BaSDR1 with improved catalytic performance toward α-tetralone 1 a were obtained by adjusting the steric hindrance and hydrophobicity of the residues that affect the approach of α-tetralone with the catalytic residues. The designed mutants also showed enhanced catalytic performance toward halogenated α-tetralones 2 a–6 a. Remarkably, the activity of the mutant Q237V/I291F toward 7-fluoro-α-tetralone 5 a was 16.3-fold higher than the wildtype enzyme with improved stereoselectivity (98.8 % ee). More notably, the mutants Q139S and Q139S/V187S exhibited decreased or reversed stereoselectivity toward α-tetralone 1 a, 5-bromo-α-tetralone 2 a, 7-fluoro-α-tetralone 5 a and 7-chloro-α-tetralone 6 a, while the relatively high ee values were obtained in the presence of 6-chloro-α-tetralone 3 a and 6-bromo-α-tetralone 4 a as substrates. Further analysis showed the larger size of the substrates was beneficial for the substrates binding to the active cavity with a more specific binding mode, which endows the reaction with higher stereoselectivity. Moreover, the recombinant E. coli expressing the variant Q237V/I291F successfully catalyzed the reduction of a high concentration 7-fluoro-α-tetralone 5 a. These results not only offered a potential tool for chiral α-tetralols, but also provided guiding information for the enzyme engineering toward bulky-bulky ketones.
- Li, Aipeng,Ting, Wang,Yang, Ke,Zhang, Xuanshuo,Yin, Dongming,Qin, Yong,Zhang, Lianbing
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- Designer Outer Membrane Protein Facilitates Uptake of Decoy Molecules into a Cytochrome P450BM3-Based Whole-Cell Biocatalyst
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We report an OmpF loop deletion mutant, which improves the cellular uptake of external additives into an Escherichia coli whole-cell biocatalyst. Through co-expression of the OmpF mutant with wild-type P450BM3 in the presence of decoy molecules, the yield
- Karasawa, Masayuki,Shoji, Osami,Stanfield, Joshua Kyle,Suzuki, Kazuto,Yonemura, Kai
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supporting information
(2021/12/16)
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- Ru-catalyzed mechanochemical asymmetric transfer hydrogenations in aqueous media using chitosan as chirality source
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As the demand for sustainable methods increases, synthetic chemistry is focusing on the application of environmentally benign methods, such as fast reactions induced by alternative energy transmission. Chitosan is a chiral biopolymer of natural origin, which can be used in asymmetric catalysis. The application of Ru-chitosan complexes along with the mechanochemical activation may open great opportunities for sustainable preparation of optically pure alcohols. In the present study, we optimized the mechanochemical asymmetric transfer hydrogenation of 4-chromanone, carried out in a mixing mill. The reaction was catalyzed by the in situ formed Ru-chitosan complex, applying HCOONa as the hydrogen donor in aqueous media. We examined the mechanical effects of different grinding media sizes, then explored the scope of the system using 24 prochiral ketones, which ranged from hetero- and carbocyclic ketones to acetophenone derivatives. In most of the cases, the reactions were successfully scaled up to 1 mmol and the products were isolated in good yields and outstanding enantioselectivities. Our present study is a significant step forward to the development of environmentally benign and sustainable enantioselective processes, as the alternative activation method provided optically enriched alcohols using a biodegradable chirality source in aqueous media.
- Kolcsár, Vanessza Judit,Sz?ll?si, Gy?rgy
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- Chiral Yolk-Shell MOF as an Efficient Nanoreactor for Asymmetric Catalysis in Organic-Aqueous Two-Phase System
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It remains a great challenge to introduce large and efficient homogeneous asymmetric catalysts into MOFs and other microporous materials as well as retain their degrees of freedom. Herein, a new heterogeneous strategy of homogeneous chiral catalysts is proposed, that is, to construct a yolk-shell MOFs-confined, large-size, and highly efficient homogeneous chiral catalyst, which can be used as a nanoreactor for asymmetric catalytic reactions.
- Shi, Shunli,Zhong, Yicheng,Hu, Zhuo,Wang, Lei,Yuan, Mingwei,Ding, Shunmin,Wang, Shuhua,Chen, Chao
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supporting information
p. 12714 - 12718
(2021/09/11)
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- A NEW TEMPLATE of MITSUNOBU ACYLATE CLEAVABLE in NONALKALINE CONDITIONS
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The Mitsunobu inversion is one of the reliable methods for stereospecific substitution of chiral alcohols, but its deacylation step has limited the substrate scope. Here, we propose a new template of the Mitsunobu acylate that can be deacylated in non-alkaline treatments. The 3,4-dihydroxy-2-methylenebutanoate was selected as a template structure, and its acetonide- or bisTBS derivatives were synthesized. The latter especially showed excellent inversion efficiency (up to >99% ee) and good elimination performance for a series of secondary alcohols in near-neutral conditions. The results demonstrated the applicability of the new template for the substrates labile in alkaline conditions, such as a-hydroxyesters.
- Sai, Yusuke,Sakakibara, Yoshimichi,Shigetomi, Kengo,Ubukata, Makoto,Uraki, Yasumitsu
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p. 140 - 158
(2022/01/08)
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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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supporting information
p. 247 - 251
(2020/10/29)
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- Phase Separation-Promoted Redox Deracemization of Secondary Alcohols over a Supported Dual Catalysts System
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Unification of oxidation and reduction in a one-pot deracemization process has great significance in the preparation of enantioenriched organic molecules. However, the intrinsic mutual deactivation of oxidative and reductive catalysts and the extrinsic incompatible reaction conditions are unavoidable challenges in a single operation. To address these two issues, we develop a supported dual catalysts system to overcome these conflicts from incompatibility to compatibility, resulting in an efficient one-pot redox deracemization of secondary alcohols. During this transformation, the TEMPO species onto the outer surface of silica nanoparticles catalyze the oxidation of racemic alcohols to ketones, and the chiral Rh/diamine species in the nanochannels of the thermoresponsive polymer-coated hollow-shell mesoporous silica enable the asymmetric transfer hydrogenation (ATH) of ketones to chiral alcohols. To demonstrate the general feasibility, a series of orthogonal oxidation/ATH cascade reactions are compared to prove the compatible benefits in the elimination of their deactivations and the balance of the cascade directionality. As presented in this study, this redox deracemization process provides various chiral alcohols with enhanced yields and enantioselectivities relative to those from unsupported dual catalysts systems. Furthermore, the dual catalysts can be recycled continuously, making them an attractive feature in the application.
- Zhao, Zhitong,Wang, Chengyi,Chen, Qipeng,Wang, Yu,Xiao, Rui,Tan, Chunxia,Liu, Guohua
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p. 4055 - 4063
(2021/08/12)
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- Enantioselective direct, base-free hydrogenation of ketones by a manganese amido complex of a homochiral, unsymmetrical P-N-P′ ligand
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The use of manganese in homogeneous hydrogenation catalysis has been a recent focus in the pursuit of more environmentally benign base metal catalysts. It has great promise with its unique reactivity when coupled with metal-ligand cooperation of aminophosphine pincer ligands. Here, a manganese precatalyst Mn(P-N-P′)(CO)2, where P-N-P′ is the amido form of the ligand (S,S)-PPh2CHPhCHPhNHCH2CH2PiPr2, has been synthesized and used for base-free ketone hydrogenation. This catalyst shows exceptionally high enantioselectivity and good activity, with tolerance for base-sensitive substrates. NMR structural analysis of intermediates formed by the reaction of the amido complex with hydrogen under pressure identified a reactive hydride with an NOE contact with the syn amine proton. Computational analysis of the catalytic cycle reveals that the heterolytic splitting of dihydrogen across the MnN bond in the amido complex has a low barrier while the hydride transfer to the ketone is the turnover-limiting step. The pro-S transition state is found to be usually much lower in energy than the pro-R transition state depending on the ketone structure, consistent with the high (S) enantiomeric excess in the alcohol products. The energy to reach the transition state is higher for the distortion of the in-coming ketone than that of the hydride complex. In a one-to-one comparison with the similar iron catalyst FeH2(CO)(P-NH-P′), the manganese catalyst is found to have higher enantioselectivity, often over 95% ee, while the iron catalyst has higher activity and productivity. An explanation of these differences is provided on the basis of the more deformable iron hydride complex due to the smaller hydride ligands.
- Seo, Chris S. G.,Tsui, Brian T. H.,Gradiski, Matthew V.,Smith, Samantha A. M.,Morris, Robert H.
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p. 3153 - 3163
(2021/05/25)
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- Homochiral Dodecanuclear Lanthanide "cage in Cage" for Enantioselective Separation
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It is extremely difficult to anticipate the structure and the stereochemistry of a complex, particularly when the ligand is flexible and the metal node adopts diverse coordination numbers. When trivalent lanthanides (LnIII) and enantiopure amino acid ligands are utilized as building blocks, self-assembly sometimes yields rare chiral polynuclear structures. In this study, an enantiopure carboxyl-functionalized amino acid-based ligand with C3 symmetry reacts with lanthanum cations to give a homochiral porous coordination cage, (Δ/λ)12-PCC-57. The dodecanuclear lanthanide cage has an unprecedented octahedral "cage-in-cage"framework. During the self-assembly, the chirality is transferred from the enantiopure ligand and fixed by the binuclear lanthanide cluster to give 12 metal centers that have either Δor λ homochiral stereochemistry. The cage exhibits excellent enantioselective separation of racemic alcohols, 2,3-dihydroquinazolinones, and multiple commercially available drugs. This finding exhibits a rare example of a multinuclear lanthanide complex with a dual-walled topology and homochirality. The highly ordered self-assembly and self-sorting of flexible amino acids and lanthanides shed light on the chiral transformation between different complicated artificial systems that mimic natural enzymes.
- Zhu, Chengfeng,Tang, Haitong,Yang, Keke,Fang, Yu,Wang, Kun-Yu,Xiao, Zhifeng,Wu, Xiang,Li, Yougui,Powell, Joshua A.,Zhou, Hong-Cai
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supporting information
p. 12560 - 12566
(2021/08/23)
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- Enantioselective Hydroxylation of Benzylic C(sp3)-H Bonds by an Artificial Iron Hydroxylase Based on the Biotin-Streptavidin Technology
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The selective hydroxylation of C-H bonds is of great interest to the synthetic community. Both homogeneous catalysts and enzymes offer complementary means to tackle this challenge. Herein, we show that biotinylated Fe(TAML)-complexes (TAML = Tetra Amido Macrocyclic Ligand) can be used as cofactors for incorporation into streptavidin to assemble artificial hydroxylases. Chemo-genetic optimization of both cofactor and streptavidin allowed optimizing the performance of the hydroxylase. Using H2O2 as oxidant, up to ~300 turnovers for the oxidation of benzylic C-H bonds were obtained. Upgrading the ee was achieved by kinetic resolution of the resulting benzylic alcohol to afford up to >98% ee for (R)-tetralol. X-ray analysis of artificial hydroxylases highlights critical details of the second coordination sphere around the Fe(TAML) cofactor.
- Barnet, Maxime,Peterson, Ryan L.,Rebelein, Johannes G.,Rumo, Corentin,Serrano-Plana, Joan,Ward, Thomas R.
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supporting information
p. 10617 - 10623
(2020/07/04)
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- Palladium Complexes Bearing Chiral bis(NHC) Chelating Ligands on a Spiro Scaffold: Synthesis, Characterization, and Their Application in the Oxidative Kinetic Resolution of Secondary Alcohols
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A series of chiral bis-N-heterocyclic carbene ligands H2[(S)-1a-d]X2 (X = Br, I) on a spiro scaffold and their palladium complexes (S)-2a-d and (S)-3a,b were prepared and applied in the enantioselective oxidative kinetic resolution of secondary alcohols. The corresponding alcohols can be obtained in high yields with moderate to excellent ee values.
- Zhang, Dao,Yu, Jueqin
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p. 605 - 613
(2020/02/13)
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- One-pot kinetic resolution-Mitsunobu reaction to access optically pure compounds, using silver salts in the substitution protocol
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A practical method is developed to access chiral arylalkyl carbinols with a high yield from racemic alcohols. A one-pot enzyme mediated Kinetic Resolution followed by Mitsunobu esterification of the unreacted enantiomer of alcohol with metal acetate results in a nearly complete formation of chiral acetate. Substitution with AgOAc was found to be the most efficient, and the use of sub stoichiometric amounts of AgNO3 and excess of NaOAc affords comparable results; the protocol was further extended to introduce azide as a nucleophile.
- Raval, Hiten B.,Bedekar, Ashutosh V.
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p. 21238 - 21243
(2020/12/31)
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- Access to both enantiomers of substituted 2-tetralol analogs by a highly enantioselective reductase
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Both (S) and (R) forms of enantiomerically pure 2-tetralols, and their substituted analogs, are fundamental pharmaceutical intermediates. Here, we utilized the wild type and an engineered form of a highly enantioselective acetophenone reductase from Geotrichum candidum NBRC 4597 (GcAPRD) to produce (S)- and (R)-2-tetralols, and their substituted analogs. All mutations targeted residue Trp288, which has been shown to restrict substrate binding, but not play a direct role in catalysis. The wild type produced (S)-alcohols with excellent enantioselectivity, while the engineered forms produced either (S)- or (R)- alcohols, depending on the substituent on the aromatic ring of the substrate, indicating that enantioselectivity can be rationally controlled. As a result, we were able to produce 6-hydroxy-2-tetralol, a potential antifungal drug intermediate, with 98% ee (S) and 81% ee (R) by wild type and Trp288Ser GcAPRD, respectively. To our knowledge, this is the first report of generating chiral 6-hydroxy-2-tetralol by rational enzyme design.
- Koesoema, Afifa Ayu,Matsuda, Tomoko,Standley, Daron M.,T. sriwong, Kotchakorn,Tamura, Mayumi
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supporting information
(2020/02/11)
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- Insights into the Substrate Promiscuity of Novel Hydroxysteroid Dehydrogenases
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Hydroxysteroid dehydrogenases (HSDHs) are valuable biocatalysts for the regio- and stereoselective modification of steroids, bile acids and other steroid derivatives. In this work, we investigated the substrate promiscuity of this highly selective class of enzymes. In order to reach this goal, a preliminary search of HSDH homologues in in-house or public available (meta)genomes was carried out. Eight novel NAD(H)-dependent HSDHs, showing either 7α-, 7β-, or 12α-HSDH activity, and including, for the first time, enzymes from extremophilic microorganisms, were identified, recombinantly produced, and characterized. Among the novel HSDHs, four highly active (up to 92 U mg?1) NAD(H)-dependent 7β-HSDHs showing negligible similarity towards previously described 7β-HSDHs, were discovered. These enzymes, along with previously characterized HSDHs, were tested as biocatalysts for the stereoselective reduction of a panel of substrates including two α-ketoesters of pharmaceutical interest and selected ketones that partially resemble the structural features of steroids. All the reactions were coupled with a suitable cofactor regeneration system. Regarding the α-ketoesters, nearly all of the tested HSDHs showed a good activity toward the selected substrates, yielding the reduced α-hydroxyester with up to 99% conversions and enantiomeric excesses. On the other hand, only the 7β-HSDHs from Collinsella aerofaciens and Clostridium absonum showed appreciable activity toward more complex ketones, i. e., (±)-trans-1-decalone, but with interesting as well as different selectivity. (Figure presented.).
- Bertuletti, Susanna,Ferrandi, Erica Elisa,Marzorati, Stefano,Vanoni, Marta,Riva, Sergio,Monti, Daniela
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p. 2474 - 2485
(2020/05/06)
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- Redox-driven deracemization of secondary alcohols by sequential ether/O2-mediated oxidation and Ru-catalyzed asymmetric reduction
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The deracemization of benzylic alcohols has been achieved using a redox-driven one-pot two-step process. The racemic alcohols were oxidized by bis(methoxypropyl) ether and oxygen to give the ketone intermediates, followed by an asymmetric transfer hydrogenation with a chiral ruthenium catalyst. This compatible oxidation/reduction process gave the enantiomerically enriched alcohols with up to 95% ee values.
- Yang, Bing,Cui, Peng,Chen, Yongsheng,Liu, Qixing,Zhou, Haifeng
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supporting information
(2020/10/14)
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- Asymmetric aerobic oxidation of secondary alcohols catalyzed by poly(: N-vinyl-2-pyrrolidone)-stabilized gold clusters modified with cyclodextrin derivatives
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Surface modification of poly(N-vinyl-2-pyrrolidone)-stabilized gold clusters (1.8 ± 0.6 nm) with aminated cyclodextrins induced aerobic oxidative kinetic resolution of racemic secondary alcohols (krel = 1.2).
- Hirano, Koto,Takano, Shinjiro,Tsukuda, Tatsuya
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supporting information
p. 15033 - 15036
(2020/01/03)
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- Combining Photo-Organo Redox- and Enzyme Catalysis Facilitates Asymmetric C-H Bond Functionalization
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In this study, we combined photo-organo redox catalysis and biocatalysis to achieve asymmetric C–H bond functionalization of simple alkane starting materials. The photo-organo catalyst anthraquinone sulfate (SAS) was employed to oxyfunctionalise alkanes to aldehydes and ketones. We coupled this light-driven reaction with asymmetric enzymatic functionalisations to yield chiral hydroxynitriles, amines, acyloins and α-chiral ketones with up to 99 % ee. In addition, we demonstrate functional group interconversion to alcohols, esters and carboxylic acids. The transformations can be performed as concurrent tandem reactions. We identified the degradation of substrates and inhibition of the biocatalysts as limiting factors affecting compatibility, due to reactive oxygen species generated in the photocatalytic step. These incompatibilities were addressed by reaction engineering, such as applying a two-phase system or temporal and spatial separation of the catalysts. Using a selection of eleven starting alkanes, one photo-organo catalyst and 8 diverse biocatalysts, we synthesized 26 products and report for the model compounds benzoin and mandelonitrile > 97 % ee at gram scale.
- Zhang, Wuyuan,Fueyo, Elena Fernandez,Hollmann, Frank,Martin, Laura Leemans,Pesic, Milja,Wardenga, Rainer,H?hne, Matthias,Schmidt, Sandy
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- Identification of an Esterase Isolated Using Metagenomic Technology which Displays an Unusual Substrate Scope and its Characterisation as an Enantioselective Biocatalyst
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Evaluation of an esterase annotated as 26D isolated from a marine metagenomic library is described. Esterase 26D was found to have a unique substrate scope, including synthetic transformations which could not be readily effected in a synthetically useful manner using commercially available enzymes. Esterase 26D was more selective towards substrates which had larger, more sterically demanding substituents (i. e. iso-propyl or tert-butyl groups) on the β-carbon, which is in contrast to previously tested commercially available enzymes which displayed a preference for substrates with sterically less demanding substituents (e.g. methyl group) at the β-carbon. (Figure presented.).
- Gavin, Declan P.,Murphy, Edel J.,Foley, Aoife M.,Castilla, Ignacio Abreu,Reen, F. Jerry,Woods, David F.,Collins, Stuart G.,O'Gara, Fergal,Maguire, Anita R.
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p. 2466 - 2474
(2019/03/11)
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- Chiral Frustrated Lewis Pairs Catalyzed Highly Enantioselective Hydrosilylations of Ketones
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A highly enantioselective Piers-type hydrosilylation of simple ketones was successfully realized using a chiral frustrated Lewis pair of tri-tert-butylphosphine and chiral diene-derived borane as catalyst. A wide range of optically active secondary alcohols were furnished in 80%—99% yields with 81%—97% ee's under mild reaction conditions.
- Liu, Xiaoqin,Wang, Qiaotian,Han, Caifang,Feng, Xiangqing,Du, Haifeng
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p. 663 - 666
(2019/05/21)
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- Method for synthesizing chiral alcohol through deracemization
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The invention relates to a method for synthesizing chiral alcohol (formula I) through deracemization. The preparation method provided by the invention is one-pot asymmetric cascade reaction, and comprises the following steps: 1), with racemic alcohol (formula II) as a raw material and dipropylene glycol dimethyl ether as a solvent, reacting at 120 DEG C for 12 hours, and performing a dehydrogenation reaction to produce intermediate ketone (formula III); and 2), directly adding 2.5mol% of a chiral diamine metal ruthenium complex as a catalyst into a reaction system, with 5 equivalents of sodiumformate as a hydrogen source and a mixed solution of methanol and water as a solvent, reacting at 50 DEG C for 12 hours under the protection of nitrogen, and performing asymmetric transfer hydrogenation to obtain the chiral alcohol (formula I). The method has the advantages of environment-friendly synthesis such as a simple and mild reaction condition, step economy and atomic economy; and in addition, a substrate has a wide application range, the enantioselectivity is high, and the method has a broad application prospect in synthesis of chiral alcohol pharmaceutical intermediates and fine chemical raw materials.
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Paragraph 0080-0082
(2019/07/29)
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- Highly Enantioselective Transfer Hydrogenation of Prochiral Ketones Using Ru(II)-Chitosan Catalyst in Aqueous Media
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Unprecedentedly high enantioselectivities are obtained in the transfer hydrogenation of prochiral ketones catalyzed by a Ru complex formed in situ with chitosan chiral ligand. This biocompatible, biodegradable chiral polymer obtained from the natural chitin afforded good, up to 86 % enantioselectivities, in the aqueous-phase transfer hydrogenation of acetophenone derivatives using HCOONa as hydrogen donor. Cyclic ketones were transformed in even higher, over 90 %, enantioselectivities, whereas further increase, up to 97 %, was obtained in the transfer hydrogenations of heterocyclic ketones. The chiral catalyst precursor prepared ex situ was examined by scanning electron microscopy, FT-mid- and -far-IR spectroscopy. The structure of the in situ formed catalyst was investigated by 1H NMR spectroscopy and using various chitosan derivatives. It was shown that a Ru pre-catalyst is formed by coordination of the biopolymer to the metal by amino groups. This precursor is transformed in water insoluble Ru-hydride complex following hydrogen donor addition. The practical value of the developed method was verified by preparing over twenty chiral alcohols in good yields and optical purities. The catalyst was applied for obtaining optically pure chiral alcohols at gram scale following a single crystallization.
- Sz?ll?si, Gy?rgy,Kolcsár, Vanessza Judit
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p. 820 - 830
(2018/12/13)
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- 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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- Engineering P450LaMO stereospecificity and product selectivity for selective C-H oxidation of tetralin-like alkylbenzenes
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The P450-mediated asymmetric hydroxylation of inert C-H bonds is a chemically challenging reaction. Self-sufficient P450LaMO from the CYP116B subfamily could catalyze the transformation of 1,2,3,4-tetrahydronaphthalene to (S)-tetralol, despite its poor enantioselectivity (er 66:34) and product selectivity (the ratio of alcohol and ketone, ak, 76:24). To improve the selectivity, phenylalanine scanning and further protein engineering were performed to reshape the active pocket of P450LaMO, resulting in a mutant (T121V/Y385F/M391L) with not only improved (S)-enantioselectivity (er 98:2) but also excellent product selectivity (ak 99:1), in contrast to another mutant L97F/T121F/E282V/T283Y with complementary (R)-enantioselectivity (er 23:77). Moreover, the enantiopure (S)-alcohols formed by the P450LaMO-catalyzed oxidation of a series of alkylbenzenes are potentially important building blocks in the pharmaceutical industry. This Phe-based enantioselectivity engineering used for reshaping the active pocket of P450s could provide a guide to the protein evolution of other CYP116B members.
- Li, Ren-Jie,Li, Aitao,Zhao, Jing,Chen, Qi,Li, Ning,Yu, Hui-Lei,Xu, Jian-He
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p. 4638 - 4644
(2018/09/29)
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- Design and Assembly of a Chiral Metallosalen-Based Octahedral Coordination Cage for Supramolecular Asymmetric Catalysis
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Supramolecular containers featuring both high catalytic activity and high enantioselectivity represent a design challenge of practical importance. Herein, it is demonstrated that a chiral octahedral coordination cage can be constructed by using twelve enantiopure Mn(salen)-derived dicarboxylic acids as linear linkers and six Zn4-p-tert-butylsulfonylcalix[4]arene clusters as tetravalent four-connected vertices. The porous cage features a large hydrophobic cavity (≈3944 ?3) decorated with catalytically active metallosalen species and is shown to be an efficient and recyclable asymmetric catalyst for the oxidative kinetic resolution of racemic secondary alcohols and the epoxidation of olefins with up to >99 % enantiomeric excess. The cage architecture not only prevents intermolecular deactivation and stabilizes the Mn(salen) catalysts but also encapsulates substrates and concentrates reactants in the cavity, resulting in enhanced reactivity and enantioselectivity relative to the free metallosalen catalyst.
- Tan, Chunxia,Jiao, Jingjing,Li, Zijian,Liu, Yan,Han, Xing,Cui, Yong
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supporting information
p. 2085 - 2090
(2018/02/06)
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- Development of Ferrocene-Based Diamine-Phosphine-Sulfonamide Ligands for Iridium-Catalyzed Asymmetric Hydrogenation of Ketones
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A series of air-stable, easily accessible tridentate ferrocene-based diamine-phosphine sulfonamide (f-diaphos) ligands were successfully developed for iridium-catalyzed asymmetric hydrogenation of ketones. The f-diaphos ligands exhibited excellent enantioselectivity and superb reactivity in Ir-catalyzed asymmetric hydrogenation of ketones (for arylalkyl ketones, (S)-selectivity, up to 99.4% ee, and 100 000 TON; for diaryl ketones, (R)-selectivity, up to 98.2% ee, and 10 000 TON). This protocol could be easily conducted on gram scale, thereby providing a chance to various drugs.
- Ling, Fei,Nian, Sanfei,Chen, Jiachen,Luo, Wenjun,Wang, Ze,Lv, Yaping,Zhong, Weihui
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p. 10749 - 10761
(2018/09/06)
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- The open d-shell enforces the active space in 3d metal catalysis: Highly enantioselective chromium(ii) pincer catalysed hydrosilylation of ketones
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Bis(oxazolinyldimethylmethyl)pyrrol (PdmBox) stereodirecting ligands provided the key to the chromium(ii)-catalysed highly enantioselective hydrosilylation of ketones. A rare square planar, chiral chromium(ii) alkyl complex was found to serve as a potent precatalyst for the reduction of a broad range of aryl alkyl and dialkyl ketone derivatives. The stereoelectronic preference of the open d4 shell of chromium(ii) firmly locks the molecular catalyst in a square planar geometry giving rise to two blocked quadrants of the coordination sphere. This earth-abundant base metal catalytic platform produces the corresponding chiral alcohols in excellent isolated yields with up to 98 %ee under mild reaction conditions (-40 °C to rt) and at low catalyst loadings (as low as 0.5 mol%).
- Schiwek, Christian H.,Vasilenko, Vladislav,Wadepohl, Hubert,Gade, Lutz H.
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supporting information
p. 9139 - 9142
(2018/08/24)
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- Asymmetric Autoamplification in the Oxidative Kinetic Resolution of Secondary Benzylic Alcohols Catalyzed by Manganese Complexes
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Herein, chiral Mn–aminopyridine complexes have been shown to catalyze the oxidation of alkylarenes to enantiomerically enriched 1-arylalkanols with hydrogen peroxide. The observed enantiomeric excess values result from the direct enantioselective benzylic C?H hydroxylation, accompanied by stereoconvergent oxidative kinetic resolution of the resulting alcohol. Testing several (S,S)-bipyrrolidine derived Mn complexes has revealed a novel catalyst (6) that exhibits the best kinetic resolution in the series (krel up to 8.8), along with sufficient reactivity and efficiency (>1000 catalytic turnovers). The mechanistic study of the Mn-mediated alcohol oxidation witnesses electrophilic active species (ρ=?1.2), with rate-limiting H abstraction (kH/kD=2.2), followed by oxygen rebound and dehydration of the resulting gem-diol to form the ketone. Intriguingly, while for the resolution of the relatively bulky 1,2-diphenylethanol, krel is virtually constant throughout the reaction, for less bulky alcohols, krel increases with increasing conversion, in line with the rising optical purity of the 1-arylalkanol. The latter participates in the oxidation as an auxiliary ligand, assisting the chiral recognition. This effect is related to the previously described asymmetric autocatalysis and asymmetric autoinduction, but is not identical with either of those, with the differences being discussed. To unambiguously identify this effect, the term asymmetric autoamplification (chiral autoamplification) is proposed.
- Talsi, Evgenii P.,Samsonenko, Denis G.,Bryliakov, Konstantin P.
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p. 2599 - 2607
(2017/07/12)
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- A heterogenized chiral imino indanol complex of manganese as an efficient catalyst for aerobic epoxidation of olefins
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Herein, a new heterogenized chiral catalyst, GFC-[Mn(L)(OH)], was synthesized by grafting the complex [Mn(L)(OH)] on carbon-coated magnetic Fe3O4 nanoparticle-decorated reduced graphene oxide sheets (GFC) through an amine linkage (L = (1R,2S)-1-(N-salicylideneamino)-2-indanol). The catalyst was characterized via FT-IR, UV/vis, XRD, SEM, and vibrating sample magnetometer (VSM) techniques. It exhibited excellent activity and selectivity in the epoxidation of olefins with oxygen in the presence of isobutyraldehyde under mild conditions (conversion 38-98%; selectivity 65-98%; and enantioselectivity 58-100%, except for alpha-methylstyrene). Furthermore, the synergistic effect of the reduced graphene oxide support was observed on the increasing activity, epoxide selectivity, and enantioselectivity. The catalyst can be recovered via magnetic separation from the reaction mixture and recycled five times without any significant loss in its activity. The advantage of this development is the use of both the synergic effect of reduced graphene oxide and the magnetite nanoparticles to obtain an easily recyclable heterogeneous green catalyst. In addition, high asymmetric induction of a rigid indanol-based unit of the ligand results in high enantioselectivity.
- Abbasi, Vahideh,Hosseini-Monfared, Hassan,Hosseini, Seyed Majid
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p. 9866 - 9874
(2017/09/18)
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- CO2-expanded bio-based liquids as novel solvents for enantioselective biocatalysis
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For the first time, CO2-expanded bio-based liquids were reported as novel and sustainable solvents for biocatalysis. Herein, it was found that by expansion with CO2, 2-methyltetrahydrofuran (MeTHF), and other bio-based liquids, which were not favorable solvents for immobilized Candida antarctica lipase B (Novozym 435) catalyzed transesterification, were tuned into excellent reaction media. Especially, for the kinetic resolution of challenging bulky secondary substrates such as rac-1-adamantylethanol, the lipase displayed very high activity with excellent enantioselectivity (E value > 200) in CO2-expanded MeTHF (MeTHF concentration 10% v/v, 6 MPa), whereas there was almost no activity observed in conventional organic solvents.
- Hoang, Hai Nam,Nagashima, Yoshihiro,Mori, Shuichi,Kagechika, Hiroyuki,Matsuda, Tomoko
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p. 2984 - 2989
(2017/04/26)
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- Ultrafast chiral separations for high throughput enantiopurity analysis
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Recent developments in fast chromatographic enantioseparations now make high throughput analysis of enantiopurity on the order of a few seconds achievable. Nevertheless, routine chromatographic determinations of enantiopurity to support stereochemical investigations in pharmaceutical research and development, synthetic chemistry and bioanalysis are still typically performed on the 5-20 min timescale, with many practitioners believing that sub-minute enantioseparations are not representative of the molecules encountered in day to day research. In this study we develop ultrafast chromatographic enantioseparations for a variety of pharmaceutically-related drugs and intermediates, showing that sub-minute resolutions are now possible in the vast majority of cases by both supercritical fluid chromatography (SFC) and reversed phase liquid chromatography (RP-LC). Examples are provided illustrating how such methods can be routinely developed and used for ultrafast high throughput analysis to support enantioselective synthesis investigations.
- Barhate, Chandan L.,Joyce, Leo A.,Makarov, Alexey A.,Zawatzky, Kerstin,Bernardoni, Frank,Schafer, Wes A.,Armstrong, Daniel W.,Welch, Christopher J.,Regalado, Erik L.
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supporting information
p. 509 - 512
(2017/01/13)
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- A recyclable Mn-porphyrin catalyst for enantioselective epoxidation of unfunctionalized olefins using molecular dioxygen
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A magnetically separable chiral catalyst, Fe3O4/tart/Mn(TCPP)Cl, was prepared by the synthesis and immobilization of manganese-tetra(4-carboxyphenyl)porphyrin, Mn(TCPP)Cl, onto the chiral surface of magnetite nanoparticles (Fe3O4/tart-NPs; tart = l-tartaric acid) through the carboxylate groups. The solid catalyst was characterized by a variety of methods including XRD, FE-SEM, FT-IR and UV-Vis spectroscopy. The catalytic activity was tested in the epoxidation reactions of prochiral olefins with molecular oxygen. The reactions were carried out in acetonitrile as solvent with molecular oxygen in the presence of isobutyraldehyde as the stoichiometric oxidant. The catalyst showed consistently high conversion, selectivity and enantioselectivity to epoxide formation in the oxidation of a variety of terminal, cyclic and aromatic olefins. The catalyst showed little deactivation with time and it is easily recovered by magnetic filtration and could be reused four times with little or no loss in activity and selectivity.
- Farokhi, Afsaneh,Hosseini-Monfared, Hassan
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p. 5032 - 5043
(2016/07/06)
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- Enantioselective aerobic oxidation of olefins by magnetite nanoparticles at room temperature: A chiral carboxylic acid strategy
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Asymmetric oxidations of organic compounds are limited in their synthetic scope and by practical factors, such as the use of complex catalyst synthesis. A simple and cheap nanostructured catalyst system comprising magnetite nanoparticles stabilized by l-(+)-tartaric acid (Fe3O4/tart-NPs) was successfully synthesized in diethylene glycol. The catalyst was characterized by FT-IR, TGA, ICP-AES, XRPD, SEM and dynamic light scattering (DLS). The catalytic activity of Fe3O4/tart-NPs dispersion in acetonitrile in the presence of isobutyraldehyde was studied in selective aerobic oxidation of olefins to form asymmetric epoxide, an important intermediate for the synthesis of biologically active compounds. In addition, the magnetically recoverable nanocatalyst Fe3O4/tart-NPs can be conveniently separated and recovered from the reaction system by applying an external magnetic field and reused for five cycles without the loss of activity after each cycle. These results demonstrate that the heterogeneous nanocatalysts possess potential applications for green and sustainable development. As synthesized nanoparticles of Fe3O4/tart-NPs are cheap and easy to synthesize asymmetric catalysts which were prepared without the involvement of difficult and cumbersome procedures for the synthesis of complicated asymmetric ligands. Possible reaction mechanisms were outlined.
- Hadian-Dehkordi, Leila,Hosseini-Monfared, Hassan
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p. 497 - 507
(2016/01/30)
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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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- Stereospecific Synthesis of Alkenes by Eliminative Cross-Coupling of Enantioenriched sp3-Hybridized Carbenoids
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1-Aryl-1,2-dialkylethenes were generated by a sequence of electrophilic substitution, 1,2-metalate rearrangement, and β-elimination initiated by the addition of enantioenriched α-(carbamoyloxy)alkylboronates to enantioenriched lithiated carbamates. The carbenoid stereochemical pairing [i.e., “like”=(S)+(S) or “unlike”=(S)+(R)] and the elimination mechanism (syn or anti), not substituent effects, determined the configuration of the trisubstituted alkene target. For example, (Z)-2,5-diphenyl-2-pentene was produced in 70 % yield with E/Z=5:95 by a like combination of Li and B carbenoids and syn (thermal) elimination whereas the E isomer was obtained in the same yield with E/Z>98:2 by an otherwise identical process involving an unlike stereochemical pairing. The concept elaborated overcomes an intrinsic limitation of traditional strategies for direct connective alkene synthesis, which cannot realize meaningful stereochemical bias unless the alkene substituents are strongly differentiated.
- Wu, Zhenhua,Sun, Xun,Potter, Kristin,Cao, Yang,Zakharov, Lev N.,Blakemore, Paul R.
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supporting information
p. 12285 - 12289
(2016/10/13)
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- Ligand effect in racemization and dynamic kinetic resolution of alcohols: Mechanism on cymene ruthenium complexes
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A family of ruthenium complexes with different ligands was utilized in racemization of (R)-1-phenylethanol to investigate the potential influence of the ligands coordinated to the ruthenium center. Kinetic experiments showed that 16-electron cymene ruthenium complex with two chloro-bridge bonds and 18-electron ones with easily dissociative ligands are highly active for catalytic racemization of alcohols. Possible racemization mechanism for cymene ruthenium complexes was then proposed. Computational analysis of dissociation energy barrier, NBO analysis and reaction potential energy surface suggest that ligand-dissociation process is the vital step of the racemization catalyzed by cymene ruthenium complexes. Thereafter, these complexes were applied in the DKR of secondary alcohols to verify their efficiency and applicability.
- Cao, Hui,Cai, Li-Hua,Wang, Chen-Xi,Zhu, Xiao-Han,Li, Zhi-Ming,Hou, Xiu-Feng
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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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- Chiral ruthenium catalyst immobilized within magnetically retrievable mesoporous silica microcapsules for aqueous asymmetric transfer hydrogenations
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The preparation of magnetically separable silica microcapsules that incorporate in their inner shell a chiral catalyst and their application in asymmetric transfer hydrogenation reactions are described. The preparation method is based on the emulsification of an oil phase containing chloroform, a modified Noyori Ru-TsDPEN catalyst, tetraethoxysilane (TEOS), and hydrophobic magnetic nanoparticles in water in the presence of an appropriate surfactant, followed by an interfacial polycondensation process under basic conditions to generate a silica shell around the oil droplets. The resulting catalytic microreactors can be considered a "quasi-homogeneous" system because the immobilized chiral catalyst reacts in a homogeneous zone, the microcapsule core filled with an organic solvent. The catalytic activity was tested in the asymmetric transfer hydrogenation of ketones in an aqueous medium. The catalytic reactions took place only in the presence of surfactants. In addition, the judicious selection of the surfactant plays a crucial role in enhancing the reaction progress through the emulsion-solid transfer (EST) approach. The catalytic activity of the Ru-TsDPEN catalyst immobilized within the silica microcapsules was superior to the same catalyst supported on silica microspheres or linked to the backbone of a silica sol-gel matrix, which indicates the importance of the homogeneous zones for the reactions. We report the design of a "quasi-homogeneous" catalytic system, based on a modified Noyori Ru-TsDPEN catalyst confined within mesoporous silica-based microreactors, for the efficient asymmetric transfer hydrogenation of ketones in water. The new system demonstrates excellent reactivity and enantioselectivity characteristic of homogeneous catalysts, but can be easily recovered.
- Zoabi, Amani,Omar, Suheir,Abu-Reziq, Raed
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p. 2101 - 2109
(2015/05/05)
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- Ansa-Ruthenium(II) Complexes of R2NSO2DPEN-(CH2)n(η6-Aryl) Conjugate Ligands for Asymmetric Transfer Hydrogenation of Aryl Ketones
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New 3rd generation designer ansa-ruthenium(II) complexes featuring N,C-alkylene-tethered N,N-dialkylsulfamoyl-DPEN/η6-arene ligands, exhibited good catalytic performance in the asymmetric transfer hydrogenation (ATH) of various classes of (het)aryl ketones in formic acid/triethylamine mixture. In particular, benzo-fused cyclic ketones furnished 98 to >99.9% ee using a low catalyst loading.
- Ki?ic, Andrea,Stephan, Michel,Mohar, Barbara
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p. 2540 - 2546
(2015/08/18)
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- Iron achieves noble metal reactivity and selectivity: Highly reactive and enantioselective iron complexes as catalysts in the hydrosilylation of ketones
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Chiral iron alkyl and iron alkoxide complexes bearing boxmi pincers as stereodirecting ligands have been employed as catalysts for enantioselective hydrosilylation reactions with unprecedented activity and selectivity (TOF = 240 h-1 at -40 °C, ee up to 99% for alkyl aryl ketones), which match the performance of previously established noble-metal-based catalysts. This shows the potential of earth-abundant metals such as iron for replacing platinum-metals without any drawbacks for the reaction design.
- Bleith, Tim,Wadepohl, Hubert,Gade, Lutz H.
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supporting information
p. 2456 - 2459
(2015/03/04)
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- Asymmetric reduction of ketones by biocatalysis using clementine mandarin (Citrus reticulata) fruit grown in annaba or by ruthenium catalysis for access to both enantiomers
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Biocatalytic reduction of prochiral ketones using freshly ripened clementine mandarin (Citrus reticulata) in aqueous medium is reported. High enantioselectivities were observed, especially for the bioreduction of indanone 3, tetralone 4, and thiochromanone 5 with respectively 95%, 99%, and 86% enantiomeric excess (ee). Enantioselective bio- and metalcatalyzed reactions were compared. Chiral ruthenium catalysts afforded good asymmetric inductions (>75% ee) in most cases, enantiomeric excesses depending on the nature of substrate and ligand. N-aminoindanol prolinamide L3 was revealed as the best ligand for most ketones. Interestingly, for several substrates both enantiomers could be obtained using either Citrus reticulata or ruthenium complex.
- Bennamane, Manhel,Zeror, Saoussen,Aribi-Zouioueche, Louisa
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p. 205 - 210
(2015/03/18)
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- Characterization of hamster NAD+-dependent 3(17)β-hydroxysteroid dehydrogenase belonging to the aldo-keto reductase 1C subfamily
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The cDNAs for morphine 6-dehydrogenase (AKR1C34) and its homologous aldo-keto reductase (AKR1C35) were cloned from golden hamster liver, and their enzymatic properties and tissue distribution were compared. AKR1C34 and AKR1C35 similarly oxidized various xenobiotic alicyclic alcohols using NAD+, but differed in their substrate specificity for hydroxysteroids and inhibitor sensitivity. While AKR1C34 showed 3α/17β/20α-hydroxysteroid dehydrogenase activities, AKR1C35 efficiently oxidized various 3β- and 17β-hydroxysteroids, including biologically active 3β-hydroxy-5α/β-dihydro-C19/C21-steroids, dehydroepiandrosterone and 17β-estradiol. AKR1C35 also differed from AKR1C34 in its high sensitivity to flavonoids, which inhibited competitively with respect to 17β-estradiol (Ki 0.11-0.69 μM). The mRNA for AKR1C35 was expressed liver-specific in male hamsters and ubiquitously in female hamsters, whereas the expression of the mRNA for AKR1C34 displayed opposite sexual dimorphism. Because AKR1C35 is the first 3(17)β-hydroxysteroid dehydrogenase in the AKR superfamily, we also investigated the molecular determinants for the 3β-hydroxysteroid dehydrogenase activity by replacement of Val54 and Cys310 in AKR1C35 with the corresponding residues in AKR1C34, Ala and Phe, respectively. The mutation of Val54Ala, but not Cys310Phe, significantly impaired this activity, suggesting that Val54 plays a critical role in recognition of the steroidal substrate.
- Endo, Satoshi,Noda, Misato,Ikari, Akira,Tatematsu, Kenjiro,El-Kabbani, Ossama,Hara, Akira,Kitade, Yukio,Matsunaga, Toshiyuki
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p. 425 - 434
(2015/11/27)
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- Mechanistic basis for the enantioselectivity of the anaerobic hydroxylation of alkylaromatic compounds by ethylbenzene dehydrogenase
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The enantioselectivity of reactions catalyzed by ethylbenzene dehydrogenase, a molybdenum enzyme that catalyzes the oxygen-independent hydroxylation of many alkylaromatic and alkylheterocyclic compounds to secondary alcohols, was studied by chiral chromatography and theoretical modeling. Chromatographic analyses of 22 substrates revealed that this enzyme exhibits remarkably high reaction enantioselectivity toward (S)-secondary alcohols (18 substrates converted with > 99% ee). Theoretical QM:MM modeling was used to elucidate the structure of the catalytically active form of the enzyme and to study the reaction mechanism and factors determining its high degree of enantioselectivity. This analysis showed that the enzyme imposes strong stereoselectivity on the reaction by discriminating the hydrogen atom abstracted from the substrate. Activation of the pro(S) hydrogen atom was calculated to be 500 times faster than of the pro(R) hydrogen atom. The actual hydroxylation step (i.e., hydroxyl group rebound reaction to a carbocation intermediate) does not appear to be enantioselective enough to explain the experimental data (the calculated rate ratios were in the range of only 2-50 for pro(S): pro(R)-oriented OH rebound).
- Szaleniec, Maciej,Dudzik, Agnieszka,Kozik, Bart?omiej,Borowski, Tomasz,Heider, Johann,Witko, Ma?gorzata
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- CH-activating oxidative hydroxylation of 1-tetralones and related compounds with high regio- and stereoselectivity
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Mutants of P450-BM3 evolved by directed evolution are excellent catalysts in the CH-activating oxidative hydroxylation of 1-tetralone derivatives and of indanone, with unusually high regio- and enantioselectivity being observed. Similar results were achieved in the oxidative hydroxylation of tetralin and indane. The products are useful building blocks in the synthesis of a number of biologically active compounds.
- Roiban, Gheorghe-Doru,Agudo, Rubn,Ilie, Adriana,Lonsdale, Richard,Reetz, Manfred T.
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supporting information
p. 14310 - 14313
(2014/12/11)
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- Enantioselective oxidation of racemic secondary alcohols catalyzed by chiral Mn(III)-salen complex with sodium hypochlorite as oxidant
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Chiral Mn(III)-salen complex catalyzed oxidative kinetic resolution (OKR) of secondary alcohols has been achieved with cheap and easily available sodium hypochlorite (NaClO) as oxidant. The novel protocol is very efficient for the OKR of a variety of secondary alcohols at room temperature.
- Zhang, Yuecheng,Zhou, Qiao,Ma, Wenchan,Zhao, Jiquan
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p. 114 - 117
(2014/01/06)
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- Organocatalytic oxidation of secondary alcohols using 1,2-Di(1-naphthyl)-1,2-ethanediamine (NEDA)
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Diamine, 1,2-di(1-naphthyl)-1,2-ethanediamine (NEDA), efficiently catalyzes the oxidation of alcohols by using TBHP as an oxidant. Notably, secondary benzyl alcohols are oxidized in almost quantitative yields, and the catalyst also displays high activity towards even hindered cycloaliphatic secondary alcohols. With enantiopure (R,R)-NEDA, oxidative kinetic resolution can be realized and depending on the alcohol ee up to 99% are achieved.
- Al-Hunaiti, Afnan,R?is?nen, Minna,Pihko, Petri,Leskel?, Markku,Repo, Timo
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supporting information
p. 6141 - 6144
(2015/03/30)
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- Linear free-energy relationship and rate study on a silylation-based kinetic resolution: Mechanistic insights
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The substituent effect of different p-substituted triphenylsilyl chlorides on silylation-based kinetic resolutions was explored. Electron-donating groups slow down the reaction rate and improve the selectivity, while electron-withdrawing groups increase the reaction rate and decrease the selectivity. Linear free-energy relationships were found correlating both selectivity factors and initial rates to the σpara Hammett parameters. A weak correlation of selectivity factors to Charton values was also observed when just alkyl substituents were employed but was nonexistent when substituents with more electronic effects were incorporated. The rate data suggest that a significant redistribution of charge occurs in the transition state, with an overall decrease in positive charge. The linear free-energy relationship derived from selectivity factors is best understood by the Hammond postulate. Early and late transition states describe the amount of substrate participation in the transition state and therefore the difference in energy between the diastereomeric transition states of the two enantiomers. This work highlights our efforts toward understanding the mechanism and origin of selectivity in our silylation-based kinetic resolution.
- Akhani, Ravish K.,Moore, Maggie I.,Pribyl, Julia G.,Wiskur, Sheryl L.
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p. 2384 - 2396
(2014/04/17)
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- Carbohydrate-based N-heterocyclic carbenes for enantioselective catalysis
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Versatile syntheses of C2-linked and C2-symmetric carbohydrate-based imidazol(in)ium salts from functionalised amino-carbohydrate derivatives are reported. The novel NHCs were ligated to [Rh(COD)Cl]2 and evaluated in Rh-catalysed asymmetric hydrosilylation of ketones with good yields and promising enantioselectivities.
- Henderson, Alexander S.,Bower, John F.,Galan, M. Carmen
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supporting information
p. 9180 - 9183
(2015/02/19)
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- Amine-tunable ruthenium catalysts for asymmetric reduction of ketones
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A series of efficient ruthenium catalysts has been developed for the asymmetric hydrogenation and transfer hydrogenation of ketones with high reactivities and selectivities. The new chiral bisdihydrobenzooxaphosphole (BIBOP)/diamineruthenium complexes catalyzed the enantioselective hydrogenation of substrates such as aryl and heteroaryl cyclic and alkyl ketones with substrate/catalyst (S/C) ratios of up to 100,000. The opposite sense of enantioselectivity can be obtained by proper selection of a diamine with a given chirality of the phosphine. The usefulness of the new system has been demonstrated in the asymmetric hydrogenation of a complex synthetic intermediate towards cholesteryl ester transfer protein (CETP) inhibitors at S/C 20,000 on large-scale operation.
- Rodriguez, Sonia,Qu, Bo,Fandrick, Keith R.,Buono, Frederic,Haddad, Nizar,Xu, Yibo,Herbage, Melissa A.,Zeng, Xingzhong,Ma, Shengli,Grinberg, Nelu,Lee, Heewon,Han, Zhengxu S.,Yee, Nathan K.,Senanayake, Chris H.
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supporting information
p. 301 - 307
(2014/05/20)
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- Synthesis and catalytic applications of an extended range of tethered ruthenium(II)/η6-arene/diamine complexes
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A series of novel enantiopure Ru(II) complexes containing a chiral diamine and η6-arene connected by a tethering group have been prepared and were evaluated in the asymmetric reductions of a range of ketones. Changes to the level of steric hindrance and the addition of an electron-withdrawing functionality on the sulfonyl group have a significant effect on the reactivity and enantioselectivity of the catalysts.
- Hodgkinson, Roy,Jurk, Vclav,Zanotti-Gerosa, Antonio,Nedden, Hans Günter,Blackaby, Andrew,Clarkson, Guy J.,Wills, Martin
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supporting information
p. 5517 - 5524
(2015/02/19)
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- Separation of enantiopure m-substituted 1-phenylethanols in high space-time yield using Bacillus subtilis esterase
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A recombinant Bacillus subtilis esterase (BsE) expressed in E. coli was found to exhibit excellent enantioselectivity (E was always greater than 100) towards m-substituted 1-phenylethanol acetates in the enantioselective hydrolysis reaction. An explanation for the high enantioselectivity observed towards these substrates was provided by molecular modeling. Moreover, the BsE also showed strong tolerance towards a high concentration of m-substituted 1-phenylethanol acetates (up to 1 M). Based on these excellent catalytic properties of BsE, a kind of m-substituted 1-phenylethanols, (R)-1-(3-chlorophenyl)ethanol, was efficiently synthesized in space-time yield of 920 g per L per day and 97% ee, indicating that the BsE was considered as a potentially ideal and promising biocatalyst for large-scale production of optically active m-substituted 1-phenylethanols. The Royal Society of Chemistry 2013.
- Zheng, Gao-Wei,Liu, Xu-Yun,Zhang, Zhi-Jun,Tian, Ping,Lin, Guo-Qiang,Xu, Jian-He
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p. 20446 - 20449
(2013/11/06)
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