- Cinchona-Alkaloid-Derived NNP Ligand for Iridium-Catalyzed Asymmetric Hydrogenation of Ketones
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Most ligands applied for asymmetric hydrogenation are synthesized via multistep reactions with expensive chemical reagents. Herein, a series of novel and easily accessed cinchona-alkaloid-based NNP ligands have been developed in two steps. By combining [Ir(COD)Cl]2, 39 ketones including aromatic, heteroaryl, and alkyl ketones have been hydrogenated, all affording valuable chiral alcohols with 96.0-99.9% ee. A plausible reaction mechanism was discussed by NMR, HRMS, and DFT, and an activating model involving trihydride was verified.
- Zhang, Lin,Zhang, Ling,Chen, Qian,Li, Linlin,Jiang, Jian,Sun, Hao,Zhao, Chong,Yang, Yuanyong,Li, Chun
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supporting information
p. 415 - 419
(2022/01/12)
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- Nickel-Catalyzed Enantioselective Hydroboration of Vinylarenes
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The enantioselective hydroboration of vinylarenes catalyzed by a chiral, nonracemic nickel catalyst is presented as a facile method for generating chiral benzylic boronate esters. Various vinylarenes react with bis(pinacolato)diboron (B2pin2) in the presence of MeOH as a hydride source to form chiral boronate esters in up to 92% yield with up to 94% ee. The use of anhydrous Me4NF to activate B2pin2 is crucial for ensuring fast transmetalation to achieve high enantioselectivities.
- Tran, Hai N.,Stanley, Levi M.
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supporting information
p. 395 - 399
(2021/12/27)
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- Visible-Light-Driven Catalytic Deracemization of Secondary Alcohols
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Deracemization of racemic chiral compounds is an attractive approach in asymmetric synthesis, but its development has been hindered by energetic and kinetic challenges. Here we describe a catalytic deracemization method for secondary benzylic alcohols which are important synthetic intermediates and end products for many industries. Driven by visible light only, this method is based on sequential photochemical dehydrogenation followed by enantioselective thermal hydrogenation. The combination of a heterogeneous dehydrogenation photocatalyst and a chiral molecular hydrogenation catalyst is essential to ensure two distinct pathways for the forward and reverse reactions. These reactions convert a large number of racemic aryl alkyl alcohols into their enantiomerically enriched forms in good yields and enantioselectivities.
- Hu, Xile,Zhang, Zhikun
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supporting information
p. 22833 - 22838
(2021/09/09)
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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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- 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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- 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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- Arene-Immobilized Ru(II)/TsDPEN Complexes: Synthesis and Applications to the Asymmetric Transfer Hydrogenation of Ketones
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The Noyori-Ikariya (arene)Ru(II)/TsDPEN precatalyst has been anchored to amorphous silica and DAVISIL through the η6-coordinated arene ligand via a straightforward synthesis and the derived systems, (arene)Ru(II)/TsDPEN@silica and (arene)Ru(II)/TsDPEN@DAVISIL, form highly efficient catalysts for the asymmetric transfer hydrogenation of a range of electron-rich and electron-poor aromatic ketones, giving good conversion and excellent ee's under mild reaction conditions. Moreover, catalyst generated in situ immediately prior to addition of substrate and hydrogen donor, by reaction of silica-supported [(arene)RuCl2]2 with (S,S)-TsDPEN, was as efficient as that generated from its preformed counterpart [(arene)Ru{(S,S)-TsDPEN}Cl]@silica. Gratifyingly, the initial TOFs (up to 1085 h?1) and ee's (96–97 %) obtained with these catalysts either rivalled or outperformed those previously reported for catalysts supported by either silica or polymer immobilized through one of the nitrogen atoms of TsDPEN. While the high ee's were also maintained during recycle studies, the conversion dropped steadily over the first three runs due to gradual leaching of the ruthenium.
- Doherty, Simon,Knight, Julian G.,Alshaikh, Hind,Wilson, James,Waddell, Paul G.,Wills, Corinne,Dixon, Casey M.
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supporting information
p. 226 - 235
(2020/12/31)
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- Polydopamine-Encapsulated Dendritic Organosilica Nanoparticles as Amphiphilic Platforms for Highly Efficient Heterogeneous Catalysis in Water
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Aqueous heterogeneous catalysis is a green, sustainable catalytic process that attracts increasing attention, but it often suffers from poor mass transfer, substrate adsorption and catalyst dispersion. Herein, we synthesized a type of amphiphilic core-shell catalysts with a hydrophilic polydopamine (PDA) shell and a hydrophobic dendritic organosilica nanoparticle (DON) core for heterogeneous catalysis in water. The hydrophilic shell allowed the catalyst dispersing well in water, and the hydrophobic core facilitated the absorption of organic reactants. The hierarchical core-shell structure facilitated rational arrangement of the location of catalytic species to match the reaction sequence. The obtained metal, enzyme and metal-enzyme amphiphilic catalysts demonstrated improved stability, selectivity and activity in aqueous reactions, including Pd-catalyzed cross-couplings (Suzuki, Liebeskind-Srogl, Heck and Sonogashira), enzymatic enantioselective reduction, chemoenzymatic cascade synthesis of chiral compounds and chemoenzymatic cascade degradation of organophosphates. The amphiphilic catalysts could be easily in situ recovered, and their high catalytic performance was sustained for five cycles.
- Gao, Jing,Guo, Na,Jiang, Yanjun,Liu, Guanhua,Liu, Pengbo,Liu, Yunting,Wang, Zihan,Zhang, Lei
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supporting information
p. 1975 - 1982
(2021/06/09)
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- An industrial perspective fermentative bioreduction of aromatic ketones by Penicillium rubens VIT SS1 and Penicillium citrinum VIT SS2
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Microbial mediated, especially the fungi mediated asymmetric reduction of the ketone is one of the most promising tools for the synthesis of chiral alcohols. Many fungal cultures were isolated from soil and screened for the stereo selective bioreduction of acetophenone. The potential isolates are characterised using molecular techniques and found to be Penicillium rubens VIT SS1 (Genbank ID: MK063869) and Penicillium citrinum VIT SS2 (Genbank ID: MW960208). Both the isolates were tested for the bioreduction of few aromatic ketones such as 4-fluoro acetophenone, 3-hydroxy acetophenone, and oxcarbazepine, which are the key chiral intermediates of various pharmaceutical drugs. The P. rubens VIT SS1 produced (S)-alcohol obeying Prelog’s rule, and P. citrinum was anti-Prelog configuration in nature. Preparatory scale reactions were conducted using the optimised bioreduction process, and the keto loading was significantly increased by 12-fold (from 0.5 to 6 g/L) with >99% conversion and >98% enantiomeric excess. The study discloses the vast prospective approach of exploring filamentous fungi for sustainable synthesis of chiral alcohols in an environment-friendly, novel, and cost competent way.
- Jothi, Saravanan,Vuppu, Suneetha
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- One-Pot Chemoenzymatic Conversion of Alkynes to Chiral Amines
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A one-pot chemoenzymatic sequential cascade for the synthesis of chiral amines from alkynes was developed. In this integrated approach, just ppm amounts of gold catalysts enabled the conversion of alkynes to ketones (>99%) after which a transaminase was used to catalyze the production of biologically valuable chiral amines in a good yield (up to 99%) and enantiomeric excess (>99%). A preparative scale synthesis of (S)-methylbenzylamine and (S)-4-methoxy-methylbenzylamine from its alkyne form gave a yield of 59 and 92%, respectively, withee> 99%.
- Mathew, Sam,Renn, Dominik,Rueping, Magnus,Sagadevan, Arunachalam
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p. 12565 - 12569
(2021/10/21)
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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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- C3 The symmetry contains a chiral ligand H3L of an amide bond. Preparation method and application
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The invention discloses C. 3 Chiral ligand H with symmetric amide bond3 L Relates to the technical field of material chemistry and chiral chemistry. The invention further provides the chiral ligand H. 3 L Preparation method and application thereof. The present invention has the advantage that the chiral ligand H of the present invention is a chiral ligand. 3 The L has a higher C. 3 The symmetric and flexible amide group enables coordination of the lanthanide metal ions with high coordination number and high oxygen affinity to be assembled into a novel structure-structure lanthanide metal chiral porous coordination cage. Moreover, the abundant chiral amide groups and amino acid residues on the ligand framework can be directly introduced into the synthesized lanthanide metal chiral porous coordination cage, thereby being beneficial to generating multiple chiral recognition sites and unique chiral microenvironments which mimic the biological enzyme binding pocket and further realize the purpose of high enantioselectivity separation of a series of chiral small molecule compounds.
- -
-
Paragraph 0092-0099
(2021/09/08)
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- Tridentate nitrogen phosphine ligand containing arylamine NH as well as preparation method and application thereof
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The invention discloses a tridentate nitrogen phosphine ligand containing arylamine NH as well as a preparation method and application thereof, and belongs to the technical field of organic synthesis. The tridentate nitrogen phosphine ligand disclosed by the invention is the first case of tridentate nitrogen phosphine ligand containing not only a quinoline amine structure but also chiral ferrocene at present, a noble metal complex of the type of ligand shows good selectivity and extremely high catalytic activity in an asymmetric hydrogenation reaction, meanwhile, a cheap metal complex of the ligand can also show good selectivity and catalytic activity in the asymmetric hydrogenation reaction, and is very easy to modify in the aspects of electronic effect and space structure, so that the ligand has huge potential application value. A catalyst formed by the ligand and a transition metal complex can be used for catalyzing various reactions, can be used for synthesizing various drugs, and has important industrial application value.
- -
-
Paragraph 0095-0102; 0105-0109
(2021/06/26)
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- Method for synthesizing chiral secondary alcohol compound
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The invention discloses a method for synthesizing a chiral secondary alcohol compound. The method comprises the following step of: reacting a ketone compound in an aprotic organic solvent at room temperature and inert gas atmosphere under the action of a chiral cobalt catalyst and an activating agent by taking a combination of bis(pinacolato)diboron and alcohol or water as a reducing agent to obtain the chiral secondary alcohol compound. According to the method disclosed by the invention, a combination of pinacol diborate and alcohol or water which are cheap, stable and easy to obtain is taken as a reducing agent, and a ketone compound is efficiently reduced to synthesize a corresponding chiral secondary alcohol compound in an aprotic organic solvent under the action of a chiral cobalt catalyst; in a chiral cobalt catalyst adopted by the method, when a chiral ligand is PAOR, an activating agent is NaBHEt3 or NaOtBu and an adopted raw material is aromatic ketone, the yield is 80% or above, and the optical purity is 90% or above; and when the adopted raw material is alkane ketone, the yield can reach 70% or above, and the optical purity can reach 80% or above.
- -
-
Paragraph 0038-0043; 0064-0068
(2021/05/29)
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- Highly Active Cooperative Lewis Acid—Ammonium Salt Catalyst for the Enantioselective Hydroboration of Ketones
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Enantiopure secondary alcohols are fundamental high-value synthetic building blocks. One of the most attractive ways to get access to this compound class is the catalytic hydroboration. We describe a new concept for this reaction type that allowed for exceptional catalytic turnover numbers (up to 15 400), which were increased by around 1.5–3 orders of magnitude compared to the most active catalysts previously reported. In our concept an aprotic ammonium halide moiety cooperates with an oxophilic Lewis acid within the same catalyst molecule. Control experiments reveal that both catalytic centers are essential for the observed activity. Kinetic, spectroscopic and computational studies show that the hydride transfer is rate limiting and proceeds via a concerted mechanism, in which hydride at Boron is continuously displaced by iodide, reminiscent to an SN2 reaction. The catalyst, which is accessible in high yields in few steps, was found to be stable during catalysis, readily recyclable and could be reused 10 times still efficiently working.
- Titze, Marvin,Heitk?mper, Juliane,Junge, Thorsten,K?stner, Johannes,Peters, René
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supporting information
p. 5544 - 5553
(2021/02/05)
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- Mechanochemical, Water-Assisted Asymmetric Transfer Hydrogenation of Ketones Using Ruthenium Catalyst
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Asymmetric catalytic reactions are among the most convenient and environmentally benign methods to obtain optically pure compounds. The aim of this study was to develop a green system for the asymmetric transfer hydrogenation of ketones, applying chiral Ru catalyst in aqueous media and mechanochemical energy transmission. Using a ball mill we have optimized the milling parameters in the transfer hydrogenation of acetophenone followed by reduction of various substituted derivatives. The scope of the method was extended to carbo- and heterocyclic ketones. The scale-up of the developed system was successful, the optically enriched alcohols could be obtained in high yields. The developed mechanochemical system provides TOFs up to 168 h?1. Our present study is the first in which mechanochemically activated enantioselective transfer hydrogenations were carried out, thus, may be a useful guide for the practical synthesis of optically pure chiral secondary alcohols.
- Kolcsár, Vanessza Judit,Sz?ll?si, Gy?rgy
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- Engineering a homochiral metal-organic framework based on an amino acid for enantioselective separation
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A chiral metal-organic framework possessing an open amphiphilic channel is constructed from a dicarboxylate ligand derived from an amino acid and is shown to be an efficient and recyclable chiral solid adsorbent, which is capable of separating racemic secondary alcohols, epoxides, and ibuprofen with very high enantioselectivity.
- Tang, Haitong,Yang, Keke,Wang, Kun-Yu,Meng, Qi,Wu, Fan,Fang, Yu,Wu, Xiang,Li, Yougui,Zhang, WenCheng,Luo, Yunfei,Zhu, Chengfeng,Zhou, Hong-Cai
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p. 9016 - 9019
(2020/08/17)
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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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- Enantioselective Hydroboration of Ketones Catalyzed by Rare-Earth Metal Complexes Containing Trost Ligands
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Four chiral dinuclear rare-earth metal complexes [REL1]2 (RE = Y(1), Eu(2), Nd(3), La (4)) stabilized by Trost proligand H3L1 (H3L1 = (S,S)-2,6-bis[2-(hydroxydiphenylmethyl)pyrrolidin-1-ylmethyl]-4-methylphenol) were first prepared, and all were characterized by X-ray diffraction. Complex 4 was employed as the catalyst for enantioselective hydroboration reaction of substituted ketones, and the corresponding secondary alcohols with excellent yields and high ee values were obtained using reductant HBpin. The same result was also achieved using the combination of lanthanium amides La[N(SiMe3)2]3 with Trost proligand H3L1 in a 1:1 molar ratio. The experimental findings and DFT calculation revealed the possible mechanism of the enantioselective hydroboration reaction and defined the origin of the enantioselectivity in the current system.
- Lu, Chengrong,Sun, Yuli,Xue, Mingqiang,Zhao, Bei
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p. 10504 - 10513
(2020/09/23)
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- Control of enantioselectivity in the enzymatic reduction of halogenated acetophenone analogs by substituent positions and sizes
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We utilized acetophenone reductase from Geotrichum candidum NBRC 4597 (GcAPRD), wild type and Trp288Ala mutant, to reduce halogenated acetophenone analogs to their corresponding (S)- and (R)-alcohols beneficial as pharmaceutical intermediates. Reduction by wild type resulted in excellent (S)-enantioselectivity for all of the substrates tested. Meanwhile, reduction by Trp288Ala resulted in high (R)-enantioselectivity for the reduction of 4′ substituted acetophenone and 2′-trifluoromethylacetophenone. In addition to that, we were able to control the enantioselectivity of Trp288Ala by the positions and sizes of the halogen substituents.
- Koesoema, Afifa Ayu,Standley, Daron M.,Ohshima, Shusuke,Tamura, Mayumi,Matsuda, Tomoko
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supporting information
(2020/03/23)
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- Iridium-Catalyzed Enantioselective Transfer Hydrogenation of Ketones Controlled by Alcohol Hydrogen-Bonding and sp3-C?H Noncovalent Interactions
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Iridium-catalyzed enantioselective transfer hydrogenation of ketones with formic acid was developed using a prolinol-phosphine chiral ligand. Cooperative action of the iridium atom and the ligand through alcohol-alkoxide interconversion is crucial to facilitate the transfer hydrogenation. Various ketones including alkyl aryl ketones, ketoesters, and an aryl heteroaryl ketone were competent substrates. An attractive feature of this catalysis is efficient discrimination between the alkyl and aryl substituents of the ketones, promoting hydrogenation with the identical sense of enantioselection regardless of steric demand of the alkyl substituent and thus resulting in a rare case of highly enantioselective transfer hydrogenation of tert-alkyl aryl ketones. Quantum chemical calculations revealed that the sp3-C?H/π interaction between an sp3-C?H bond of the prolinol-phosphine ligand and the aryl substituent of the ketone is crucial for the enantioselection in combination with O?H???O/sp3-C?H???O two-point hydrogen-bonding between the chiral ligand and carbonyl group. (Figure presented.).
- Murayama, Hiroaki,Heike, Yoshito,Higashida, Kosuke,Shimizu, Yohei,Yodsin, Nuttapon,Wongnongwa, Yutthana,Jungsuttiwong, Siriporn,Mori, Seiji,Sawamura, Masaya
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supporting information
p. 4655 - 4661
(2020/07/13)
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- Optimisation, scope and advantages of the synthesis of chiral phenylethanols using whole seeds of Bauhinia variegata L. (Fabaceae) as a new and stereoselective bio-reducer of carbonyl compounds
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With the aim of finding new methods for environmentally friendly synthesis of chiral phenylethanols, a screening was carried out to identify seeds that could be used as a biocatalyst capable of reducing stereoselectively prochiral ketones. As a result, seeds of Bauhinia variegata L. (Fabaceae) were identified as being an efficient and stereoselective biological reducer of acetophenone to produce (S)-1-phenylethanol (conversion of 98% and 99 e.e.%). Then, to optimise the reductive process, the effects of some variables such as temperature, load of substrate, pH, co-solvent, and reuse and storability of the seeds as a function of time were established. Utilising the optimal reaction conditions, nineteen substituted acetophenones were reduced to their corresponding chiral alcohols with a conversion ranging from 30% to 98% and enantiomeric excess of between 65% and >99%, and in addition, useful key intermediates were also obtained by the synthesis of drugs. The scope and advantages of this new biocatalytic synthetic method are also discussed.Research highlights A screening was carried out to identify seeds that could be used as a biocatalyst Seeds of Bauhinia variegata have been identified as an efficient biocatalyst to reduce carbonyl compounds. Acetophenone and substituted acetophenones were reduced with high stereoselectivity. Some key intermediates were synthetised using this methodology. Seeds can be stored for twenty-four months without loss of activity.
- Aimar, Mario L.,Bordón, Daniela L.,Cantero, Juan J.,Decarlini, María F.,Demmel, Gabriela I.,Rossi, Laura I.,Ruiz, Gustavo M.,Vázquez, Ana M.
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- Cationic NHC-Phosphine Iridium Complexes: Highly Active Catalysts for Base-Free Hydrogenation of Ketones
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Novel bidentate N-heterocyclic carbene-phosphine iridium complexes have been synthesized and evaluated in the hydrogenation of ketones. Reported catalytic systems require base additives and, if excluded, need elevated temperature or high pressure of hydrogen gas to achieve satisfactory reactivity. The developed catalysts showed extremely high reactivity and good enantioselectivity under base-free and mild conditions. In the presence of 1 mol % catalyst under 1 bar hydrogen pressure at room temperature, hydrogenation was complete in 30 minutes giving up to 96 % ee. Again, this high reactivity was achieved in additive-free conditions. Mechanistic experiments demonstrated that balloon pressure of hydrogen was sufficient to form the activate species by reducing and eliminating the 1,5-cyclooctadiene ligand. The pre-activated catalyst was able to hydrogenate acetophenone with 89 % conversion in 5 min.
- Quan, Xu,Kerdphon, Sutthichat,Peters, Bram B. C.,Rujirawanich, Janjira,Krajangsri, Suppachai,Jongcharoenkamol, Jira,Andersson, Pher G.
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supporting information
p. 13311 - 13316
(2020/09/22)
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- Imine containing C2-Symmetric chiral half sandwich η6-p-cymene-Ru(II)- phosphinite complexes: Investigation of their catalytic activity in the asymmetric transfer hydrogenation of ketones
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New chiral C2-symmetric bis(phosphinite) ligands containing imine group were synthesized from 1-({[(1R,2R)-2-{[(2-hydroxynaphthalen-1-yl)methylidene] amino}cyclohexyl]- imino}methyl)- naphthalen-2-ol and two equivalents of Ph2PCl, (i-Pr)2PCl or (Cy)2PCl, in high yields. Binuclear C2-symmetric half sandwich η6-p-cymene-Ru(II) complexes of the chiral phosphinite ligands were synthesized by treating of [Ru(η6-p-cymene)(μ-Cl)Cl]2 with the phosphinites in 1:1 M ratio in CH2Cl2. Their catalytic activities in asymmetric transfer hydrogenation (ATH) were investigated for the reaction of acetophenone derivatives with isopropyl alcohol. The corresponding optically active secondary alcohols were obtained in excellent levels of conversion (96–99%) and moderate enantioselectivity (up to 60% ee). Among three complexes investigated, complex 4 was the most efficient one.
- Saleh, Najmuldain Abdullah,Pa?a, Salih,Kayan, Cezmi,Meri?, Nermin,Sünkür, Murat,Aral, Tar?k,Aydemir, Murat,Baysal, Ak?n,Durap, Feyyaz
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- Observation of hyperpositive non-linear effect in catalytic asymmetric organozinc additions to aldehydes
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Asymmetric amplification is a phenomenon that is believed to play a key role in the emergence of homochirality in life. In asymmetric catalysis, theoretical and experimental models have been investigated to provide an understanding of how chiral amplification is possible, in particular based on non-linear effects. Interestingly, it has been proposed a quarter century ago that chiral catalysts, when not enantiopure might even be more enantioselective than their enantiopure counterparts. We show here that such hyperpositive non-linear effect in asymmetric catalysis is indeed possible. An in-depth study into the underlying mechanism was carried out, and the scheme we derive differs from the previous proposed models.
- Geiger, Yannick,Achard, Thierry,Maisse-Fran?ois, Aline,Bellemin-Laponnaz, Stéphane
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supporting information
p. 1250 - 1256
(2020/07/25)
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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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- Activity and specificity studies of the new thermostable esterase EstDZ2
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In this paper, we study the activity and specificity of EstDZ2, a new thermostable carboxyl esterase of unknown function, which was isolated from a metagenome library from a Russian hot spring. The biocatalytic reaction employing EstDZ2 proved to be an efficient method for the hydrolysis of aryl p-, o- or m-substituted esters of butyric acid and esters of secondary alcohols. Docking studies revealed structural features of the enzyme that led to activity differences among the different substrates.
- Myrtollari, Kamela,Katsoulakis, Nikolaos,Zarafeta, Dimitra,Pavlidis, Ioannis V.,Skretas, Georgios,Smonou, Ioulia
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- RETRACTED ARTICLE: The Manganese(I)-Catalyzed Asymmetric Transfer Hydrogenation of Ketones: Disclosing the Macrocylic Privilege
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The bis(carbonyl) manganese(I) complex [Mn(CO)2(1)]Br (2) with a chiral (NH)2P2 macrocyclic ligand (1) catalyzes the asymmetric transfer hydrogenation of polar double bonds with 2-propanol as the hydrogen source. Ketones (43 substrates) are reduced to alcohols in high yields (up to >99 %) and with excellent enantioselectivities (90–99 % ee). A stereochemical model based on attractive CH–π interactions is proposed.
- Passera, Alessandro,Mezzetti, Antonio
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supporting information
p. 187 - 191
(2019/12/11)
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- C1-Symmetric PNP Ligands for Manganese-Catalyzed Enantioselective Hydrogenation of Ketones: Reaction Scope and Enantioinduction Model
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A family of ferrocene-based chiral PNP ligands is reported. These tridentate ligands were successfully applied in Mn-catalyzed asymmetric hydrogenation of ketones, giving high enantioselectivities (92%~99% ee for aryl alkyl ketones) as well as high efficiencies (TON up to 2000). In addition, dialkyl ketones could also be hydrogenated smoothly. Manganese intermediates that might be involved in the catalytic cycle were analyzed. DFT calculation was carried out to help understand the chiral induction model. The Mn/PNP catalyst could discriminate two groups with different steric properties by deformation of the phosphine moiety in the flexible 5-membered ring.
- Zeng, Liyao,Yang, Huaxin,Zhao, Menglong,Wen, Jialin,Tucker, James H. R.,Zhang, Xumu
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p. 13794 - 13799
(2020/11/30)
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- Efficient asymmetric synthesis of chiral alcohols using high 2-propanol tolerance alcohol dehydrogenase: Sm ADH2 via an environmentally friendly TBCR system
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Alcohol dehydrogenases (ADHs) together with the economical substrate-coupled cofactor regeneration system play a pivotal role in the asymmetric synthesis of chiral alcohols; however, severe challenges concerning the poor tolerance of enzymes to 2-propanol and the adverse effects of the by-product, acetone, limit its applications, causing this strategy to lapse. Herein, a novel ADH gene smadh2 was identified from Stenotrophomonas maltophilia by traditional genome mining technology. The gene was cloned into Escherichia coli cells and then expressed to yield SmADH2. SmADH2 has a broad substrate spectrum and exhibits excellent tolerance and superb activity to 2-propanol even at 10.5 M (80%, v/v) concentration. Moreover, a new thermostatic bubble column reactor (TBCR) system is successfully designed to alleviate the inhibition of the by-product acetone by gas flow and continuously supplement 2-propanol. The organic waste can be simultaneously recovered for the purpose of green synthesis. In the sustainable system, structurally diverse chiral alcohols are synthesised at a high substrate loading (>150 g L-1) without adding external coenzymes. Among these, about 780 g L-1 (6 M) ethyl acetoacetate is completely converted into ethyl (R)-3-hydroxybutyrate in only 2.5 h with 99.9% ee and 7488 g L-1 d-1 space-time yield. Molecular dynamics simulation results shed light on the high catalytic activity toward the substrate. Therefore, the high 2-propanol tolerance SmADH2 with the TBCR system proves to be a potent biocatalytic strategy for the synthesis of chiral alcohols on an industrial scale.
- Yang, Zeyu,Fu, Hengwei,Ye, Wenjie,Xie, Youyu,Liu, Qinghai,Wang, Hualei,Wei, Dongzhi
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- Porous Organic Frameworks Featured by Distinct Confining Fields for the Selective Hydrogenation of Biomass-Derived Ketones
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The asymmetric hydrogenation of biomass-derived molecules for the preparation of single enantiomer compounds is an effective method to reduce the rapid consumption of fossil resources. Porous organic frameworks (POFs) with pure organic surfaces may provide unusual confinement effects for organic substrates in chiral catalysis. Here, a series of POF catalysts are designed with chiral active centers decorated into sharply defined one-dimensional channels with diameters in the range of 1.2–2.9 nm. Due to the synergistic effect originating from the conjugated inner wall, the POF material (aperture size 2.4 nm) concentrates over 90% of aromatic species into the porous architecture, and its affinity is one or two orders of magnitude higher than those of classical porous solids. As determined by PBE+D3 calculation, the phenyl fragment reveals strong π–π interaction for steric hindrance around the metal active site to achieve stronger asymmetric induction. Therefore, this POF catalyst achieves high conversion (>99% yield) and enantioselectivity (>99% ee) for various substrates. The advantages of using the POF platform as a chiral catalyst can provide new perspectives on POF-based solid-state host–guest chemistry and asymmetric heterogeneous catalysis.
- Yang, Yajie,Deng, Dan,Zhang, Shenli,Meng, Qinghao,Li, Zhangnan,Wang, Zeyu,Sha, Haoyan,Faller, Roland,Bian, Zheng,Zou, Xiaoqin,Zhu, Guangshan,Yuan, Ye
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- Efficient Asymmetric Synthesis of Ethyl (S)-4-Chloro-3-hydroxybutyrate Using Alcohol Dehydrogenase SmADH31 with High Tolerance of Substrate and Product in a Monophasic Aqueous System
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Bioreductions catalyzed by alcohol dehydrogenases (ADHs) play an important role in the synthesis of chiral alcohols. However, the synthesis of ethyl (S)-4-chloro-3-hydroxybutyrate [(S)-CHBE], an important drug intermediate, has significant challenges concerning high substrate or product inhibition toward ADHs, which complicates its production. Herein, we evaluated a novel ADH, SmADH31, obtained from the Stenotrophomonas maltophilia genome, which can tolerate extremely high concentrations (6 M) of both substrate and product. The coexpression of SmADH31 and glucose dehydrogenase from Bacillus subtilis in Escherichia coli meant that as much as 660 g L-1 (4.0 M) ethyl 4-chloroacetoacetate was completely converted into (S)-CHBE in a monophasic aqueous system with a >99.9% ee value and a high space-time yield (2664 g L-1 d-1). Molecular dynamics simulation shed light on the high activity and stereoselectivity of SmADH31. Moreover, five other optically pure chiral alcohols were synthesized at high concentrations (100-462 g L-1) as a result of the broad substrate spectrum of SmADH31. All these compounds act as important drug intermediates, demonstrating the industrial potential of SmADH31-mediated bioreductions.
- Chen, Rong,Liu, Qinghai,Wang, Hualei,Wei, Dongzhi,Xie, Youyu,Yang, Zeyu,Ye, Wenjie
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p. 1068 - 1076
(2020/07/06)
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- Co-immobilization of metal and enzyme into hydrophobic nanopores for highly improved chemoenzymatic asymmetric synthesis
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Chemoenzymatic catalysts with hydrophobic nanopores were fabricated by co-immobilizing metal nanoparticles and enzymes into the dendritic organosilica nanoparticles. They demonstrated highly improved catalytic performance in chemoenzymatic asymmetric synthesis of chiral amines and alcohols. The hydrophobic microenvironment proved to be critical to enhanced stability, activity and cascade efficiency. This journal is
- Gao, Liya,Wang, Zihan,Liu, Yunting,Liu, Pengbo,Gao, Shiqi,Gao, Jing,Jiang, Yanjun
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supporting information
p. 13547 - 13550
(2020/11/17)
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- Optically active 2-amino-4-alkoxypyrimidnes derivatives as 5-HT2C agonists
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The present invention provides an optically active 2-amino-4-alkoxy pyrimidine derivative that has excellent performance as a 5-HT2C agonist but has high selectivity to 2A and 2B. The present invention provides the optically active 2-amino-4-alkoxy pyrimidine derivative having a structure of chemical formula 1.COPYRIGHT KIPO 2020
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Paragraph 0130-0136
(2019/12/25)
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- Enantiocomplementary decarboxylative hydroxylation combining photocatalysis and whole-cell biocatalysis in a one-pot cascade process
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Designing a green, highly efficient and stereoselective catalytic system to generate valuable enantioenriched products is a long-standing goal in green chemistry. Here, we report a one-pot cascade combining photocatalysts with (R)- or (S)-selective ketoreductases for the decarboxylative carbonylation of carboxylic acids and the subsequent bioreduction to generate valuable chiral alcohols. Using this approach, various chiral alcohols with complementary (R)- or (S)-configurations were prepared with good yields (up to 93%) and excellent stereoselectivity (up to 99% ee). Such a photochemo-enzymatic one-pot whole-cell process combines the advantages of both photocatalysts and enzyme catalysts and provides a mild, green, metal-free and highly stereoselective alternative in asymmetric decarboxylative hydroxylation reactions.
- Xu, Jian,Arkin, Mamatjan,Peng, Yongzhen,Xu, Weihua,Yu, Huilei,Lin, Xianfu,Wu, Qi
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supporting information
p. 1907 - 1911
(2019/04/27)
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- Deracemization of sec-alcohols through sequential application of C. Albicans and Ketoreductases
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A biocatalytic cascade process was developed using immobilized cells of the wild type yeast Candida albicans CCT 0776 in calcium alginate beads and a commercially available ketoreductase. The aim was to promote deracemization by stereoinversion of (±)-1-arylethanols in high substrate concentration (above 100 mmol L-1) to prepare the (R)-enantiomers of the alcohols (90-99percent), with a high enantiomeric excess (83-99percent) after 2 to 19 h. The (R)-1-(3-methoxyphenyl)ethanol, with 70percent yield and 91percent ee, obtained after 5 h was used to prepare (S)-1-(3-methoxyphenyl)-ethylamine with 60percent yield and 91percent ee after two steps, a key intermediate in the synthesis of (S)-rivastigmine.
- Nasário, Fábio D.,Moran, Paulo J.S.,Rodrigues, José Augusto R.
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p. 772 - 779
(2019/08/26)
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- Synthesis and biological evaluation of disubstituted pyrimidines as selective 5-HT2C agonists
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Here, we describe the synthesis of disubstituted pyrimidine derivatives and their biological evaluation as selective 5-HT2C agonists. To improve selectivity for 5-HT2C over other subtypes, we synthesized two series of disubstituted pyrimidines with fluorophenylalkoxy groups at either the 5-position or 4-position and varying cyclic amines at the 2-position. The in vitro cell-based assay and binding assay identified compounds 10a and 10f as potent 5-HT2C agonists. Further studies on selectivity to 5-HT subtypes and drug-like properties indicated that 2,4-disubstituted pyrimidine 10a showed a highly agonistic effect on the 5-HT2C receptor, with excellent selectivity, as well as exceptional drug-like properties, including high plasma and microsomal stability, along with low CYP inhibition. Thus, pyrimidine 10a could be considered a viable lead compound as a 5-HT2C selective agonist.
- Kim, Juhyeon,Kim, Yoon Jung,Londhe, Ashwini M.,Pae, Ae Nim,Choo, Hyunah,Kim, Hak Joong,Min, Sun-Joon
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- Combined Photoredox/Enzymatic C?H Benzylic Hydroxylations
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Chemical transformations that install heteroatoms into C?H bonds are of significant interest because they streamline the construction of value-added small molecules. Direct C?H oxyfunctionalization, or the one step conversion of a C?H bond to a C?O bond, could be a highly enabling transformation due to the prevalence of the resulting enantioenriched alcohols in pharmaceuticals and natural products,. Here we report a single-flask photoredox/enzymatic process for direct C?H hydroxylation that proceeds with broad reactivity, chemoselectivity and enantioselectivity. This unified strategy advances general photoredox and enzymatic catalysis synergy and enables chemoenzymatic processes for powerful and selective oxidative transformations.
- Betori, Rick C.,May, Catherine M.,Scheidt, Karl A.
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supporting information
p. 16490 - 16494
(2019/11/03)
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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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- Enantiopure Methyl- A nd Phenyllithium: Mixed (Carb-)Anionic Anisyl Fencholate-Aggregates
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Methyl- A nd phenyllithium aggregates with enantiopure anisyl fencholate units form after reaction of organolithium reagent with (+)-anisyl fenchol in hydrocarbon and some ethereal solvents. These carbanionic aggregates are characterized by X-ray crystal analyses and exhibit both 3:1 stoichiometry and distorted cubic Li4O3C1 cores, in which three lithium ions coordinate the carbanion (i.e., methylide or phenylide). These three lithium ions define a Lewis acidic surface (Li3), binding the carbanion and expanding with the steric demand of the carbanion (i.e., from Me: 2.62 ?2, over n-Bu: 2.65 ?2 (previous work) to Ph: 2.79 ?2). Methylation and phenylation reactions of various prochiral aldehydes employing these methyllithium and phenyllithium aggregates yield alcohols with up to 44% ee. To rationalize the formation of the mixed (carb-)anionic aggregates, aggregate formation energies, describing co-condensations of RLi (R = Me, Ph, n-Bu) and lithium fencholates, are computed for the 3:1 and 2:2 stoichiometries. These computed aggregate formation energies point to preferences for 3:1 over 2:2 aggregates, as it is also apparent from experimental aggregate formations, confirmed by X-ray crystal analyses. In close analogy to the X-ray crystal structures, the computed Li3 surfaces increase with increasing steric demand of the carbanions. The chiral, mixed (carb-)anionic RLi-fencholate aggregates hence adapt to different carbanion sized and arise not only with small (Me) or primary carbanions (n-Bu) but even with the larger secondary phenyl anion.
- Grote, Vanessa,Neud?rfl, J?rg-Martin,Goldfuss, Bernd
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supporting information
p. 771 - 779
(2019/02/19)
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- Diphenylamine-amine-oxazoline ligand, synthesis method as well as metal complex and application thereof
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The invention provides a diphenylamine-amine-oxazoline ligand which is a compound of formula (1) or an antipode or racemate of the compound of formula (1), wherein R1 and R2 are respectively and separately one of C1 to C10 hydrocarbon group, benzyl group, phenyl group or substituted phenyl group and heteroaryl group; and R3 is H or methyl. The invention also discloses a synthesis method as well asa metal complex and application thereof, which aims at providing a catalyst capable of realizing high synthesis yield by virtue of a simple synthesis route, and ensuring that the catalyst has very high catalytic activity in asymmetric hydrogenation and hydrogen transfer reactions of olefins and ketones.
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Paragraph 0122-0128; 0135; 0136
(2019/04/17)
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- Water soluble Ru (II)–p-cymene complexes of chiral aroylthiourea ligands derived from unprotected D/L-alanine as proficient catalysts for asymmetric transfer hydrogenation of ketones
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The newfangled chiral aroylthiourea ligands (L1-L6) were produced from unprotected D/L-alanine and their water soluble Ru (II) organometallic catalysts (1–6) were designed from their reaction with [RuCl2(η6-p-cymene)]2. The analytical and spectral methods were used to confirm the structure of the ligands and complexes. The solid state structure of L1, 5 and 6 was confirmed by single crystal XRD. The organometallic compounds (1–6) catalyzed the asymmetric transfer hydrogenation of aromatic, heteroaromatic and bulky ketones to yield respective enantiopure secondary alcohols with admirable conversions (up to 99%) and attractive enantiomeric excesses (ee up to 98%), in presence of formic acid and triethylamine in water medium under non-inert atmospheric conditions.
- Sheeba, Mani Mary,Tamizh, Manoharan Muthu,Bhuvanesh, Nattamai S.P.,Karvembu, Ramasamy
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- Compartmentalized Nanoreactors for One-Pot Redox-Driven Transformations
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This contribution introduces poly(2-oxazoline)-based shell cross-linked micelles (SCMs) as nanoreactors to realize one-pot redox-driven deracemizations of secondary alcohols in aqueous media. TEMPO and Rh-TsDPEN moieties are spatially positioned into the hydrophilic corona and the hydrophobic micelle core, respectively. TEMPO catalyzes the oxidation of racemic secondary alcohols into ketones, while Rh-TsDPEN catalyzes the asymmetric transfer hydrogenation (ATH) of these ketones to afford enantioenriched secondary alcohols. Both catalysts, the Rh-TsDPEN complex and TEMPO, are incompatible with each other and the SCMs are designed to provide indispensable catalyst site isolation. Kinetic studies show that the SCMs enhance the reactivity of the immobilized catalysts, in comparison to those for the unsupported analogues under the same reaction conditions. Our nanoreactors can perform deracemizations on a broad range of secondary alcohol substrates and are reusable in a continuous manner while maintaining high activity.
- Qu, Peiyuan,Kuepfert, Michael,Jockusch, Steffen,Weck, Marcus
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p. 2701 - 2706
(2019/03/08)
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- Enantioselective Separation over a Chiral Biphenol-Based Metal-Organic Framework
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A chiral porous 3D metal-organic framework (MOF) is constructed from an enantiopure carboxylate ligand of 1,1′-biphenol, which can be utilized as adsorbent for the separation of aromatic alcohols and sulfoxides with enantioselectivity of up to 99.4%. Single-crystal X-ray diffraction analysis reveals the binding sites and host-guest interactions clearly, providing microscopic insight into the origin of the enantiosorption in the framework.
- Abbas, Anees,Wang, Zhao-Xi,Li, Zijian,Jiang, Hong,Liu, Yan,Cui, Yong
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supporting information
p. 8697 - 8700
(2018/08/17)
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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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- Transformation of Alkynes into Chiral Alcohols via TfOH-Catalyzed Hydration and Ru-Catalyzed Tandem Asymmetric Hydrogenation
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A novel full atom-economic process for the transformation of alkynes into chiral alcohols by TfOH-catalyzed hydration coupled with Ru-catalyzed tandem asymmetric hydrogenation in TFE under simple conditions has been developed. A range of chiral alcohols was obtained with broad functional group tolerance, good yields, and excellent stereoselectivities.
- Liu, Sensheng,Liu, Huan,Zhou, Haifeng,Liu, Qixing,Lv, Jinliang
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supporting information
p. 1110 - 1113
(2018/02/23)
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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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- Easy Access to Enantiopure (S)- and (R)-Aryl Alkyl Alcohols by a Combination of Gold(III)-Catalyzed Alkyne Hydration and Enzymatic Reduction
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Chemoenzymatic one-pot processes based on the combination of metal catalysis and biocatalysis open up highly attractive perspectives regarding the production of enantiopure compounds. By combining a gold-catalyzed hydration reaction with an enzymatic reduction, we present a straightforward and atom-economical chemoenzymatic method for the synthesis of secondary alcohols with excellent optical purity. Efficient cofactor recycling exploits the solvent of the metal-catalyzed step as an auxiliary substrate for the enzymatic step.
- Schaaf, Patricia,Gojic, Vladimir,Bayer, Thomas,Rudroff, Florian,Schnürch, Michael,Mihovilovic, Marko D.
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p. 920 - 924
(2018/02/23)
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- One-pot synthesis of chiral alcohols from alkynes by CF3SO3H/ruthenium tandem catalysis
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A practical one-pot synthesis of chiral alcohols from readily available alkynes via tandem catalysis by the combination of CF3SO3H and a fluorinated chiral diamine Ru(ii) complex in aqueous CF3CH2OH is described. Very interestingly, the combination of fluorinated catalysts and solvent exhibits a positive fluorine effect on the reactivity and enantioselectivity. A range of chiral alcohols with wide functional group tolerance was obtained in high yield and excellent stereoselectivity under simple and mild conditions.
- Liu, Huan,Liu, Sensheng,Zhou, Haifeng,Liu, Qixing,Wang, Chunqin
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p. 14829 - 14832
(2018/04/30)
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- Biocompatible metal-assisted C-C cross-coupling combined with biocatalytic chiral reductions in a concurrent tandem cascade
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In this study, we present a concurrent chemo/biocatalytic one pot reaction cascade by combining a metal (Pd/Cu) assisted Liebeskind-Srogl (L-S) coupling with an enantioselective enzymatic reduction for the production of chiral amines and alcohols. The latter transformation was realized by applying enantiocomplementary alcohol dehydrogenases from Lactobacillus kefir (R-selective) and Rhodococcus ruber (S-selective). Compatibility issues were solved by investigating first the L-S-coupling protocol in water at room temperature. Subsequently, we investigated two different biphasic systems and applied a biomimicking approach to separate enzyme-deactivating components. By using a lipophilic membrane in a smart reactor design, we were able to perform concurrent catalytic cascades with overall concentrations up to 100 mM substrate and to produce 1-phenylethylamine and several chiral alcohols in high yields (up to 81% over 2 steps) and enantiomeric purity ((+) and (?)-enantiomers both with 99% ee).
- Schaaf, Patricia,Bayer, Thomas,Koley, Moumita,Schnürch, Michael,Bornscheuer, Uwe T.,Rudroff, Florian,Mihovilovic, Marko D.
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supporting information
p. 12978 - 12981
(2018/11/23)
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