- Discovery and Redesign of a Family VIII Carboxylesterase with High (S)-Selectivity toward Chiral sec-Alcohols
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Highly enantioselective lipase has been widely utilized in the preparation of versatile enantiopure chiral sec-alcohols through kinetic or dynamic kinetic resolution. Lipase is intrinsically (R)-selective, and it is difficult to obtain (S)-selective lipase. Recent crystal structures of a family VIII carboxylesterase have revealed that the spatial array of its catalytic triad is the mirror image of that of lipase but with a catalytic triad that is distinct from lipase. We, therefore, hypothesized that the family VIII carboxylesterase may exhibit (S)-enantioselectivity toward sec-alcohols similar to (S)-selective serine protease, whose catalytic triad is also spatially arrayed as its mirror image. In this study, a homologous enzyme (carboxylesterase from Proteobacteria bacterium SG_bin9, PBE) of a known family VIII carboxylesterase (pdb code: 4IVK) was prepared, which showed not only moderate (S)-selectivity toward sec-alcohols such as 3-butyn-2-ol and 1-phenylethyl alcohol but also (R)-selectivity toward particular sec-alcohols among the substrates explored. Furthermore, the (S)-selectivity of PBE has been significantly improved by rational redesign based on molecular modeling. Molecular modeling identified a binding pocket composed of Ser381, Ala383, and Arg408 for the methyl substituent of (R)-1-phenylethyl acetate and suggested that larger residues may increase the enantioselectivity by interfering with the binding of the slow-reacting enantiomer. As predicted, substituting Ser381with larger residues (Phe, Tyr, and Trp) significantly improved the (S)-selectivity of PBE toward all sec-alcohols explored, even the substrates toward which the wild-type PBE exhibits (R)-selectivity. For instance, the enantioselectivity toward 3-butyn-2-ol and 1-phenylethyl alcohol was improved from E = 5.5 and 36.1 to E = 2001 and 882, respectively, by single mutagenesis (S381F).
- Park, Areum,Park, Seongsoon
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p. 2397 - 2402
(2022/02/17)
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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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- 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.
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Paragraph 0095-0102; 0105-0109
(2021/06/26)
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- Application of robust ketoreductase from Hansenula polymorpha for the reduction of carbonyl compounds
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Enzyme-catalysed asymmetric reduction of ketones is an attractive tool for the production of chiral building blocks or precursors for the synthesis of bioactive compounds. Expression of robust ketoreductase (KRED) from Hansenula polymorpha was upscaled and applied for the asymmetric reduction of 31 prochiral carbonyl compounds (aliphatic and aromatic ketones, diketones and β-keto esters) to the corresponding optically pure hydroxy compounds. Biotransformations were performed with the purified recombinant KRED together with NADP+ recycling glucose dehydrogenase (GDH, Bacillus megaterium), both overexpressed in Escherichia coli BL21(DE3). Maximum activity of KRED for biotransformation of ethyl-2-methylacetoacetate achieved by the high cell density cultivation was 2499.7 ± 234 U g–1DCW and 8.47 ± 0.40 U·mg–1E, respectively. The KRED from Hansenula polymorpha is a very versatile enzyme with broad substrate specificity and high activity towards carbonyl substrates with various structural features. Among the 36 carbonyl substrates screened in this study, the KRED showed activity with 31, with high enantioselectivity in most cases. With several ketones, the Hansenula polymorpha KRED catalysed preferentially the formation of the (R)-secondary alcohols, which is highly valued.
- Petrovi?ová, Tatiana,Gyuranová, Dominika,Pl?, Michal,Myrtollari, Kamela,Smonou, Ioulia,Rebro?, Martin
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- Novel non-metal catalyst for catalyzing asymmetric hydrogenation of ketone and alpha, beta-unsaturated ketone
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The invention discloses a novel non-metal catalyst for catalyzing asymmetric hydrogenation of ketone and alpha, beta-unsaturated ketone. The preparation method of a chiral alcohol compound shown as formula IV comprises the following step of: reacting a ketone compound shown as formula V with hydrogen under the catalysis of tri(4-hydrotetrafluorophenyl)boron and a chiral oxazoline compound to obtain the chiral alcohol compound shown as the formula IV; the preparation method of a chiral tetralone compound shown as formula VI comprises the following step of: under the catalysis of tri(4-hydrotetrafluorophenyl)boron and a chiral oxazoline compound, reacting an alpha, beta-unsaturated ketone compound shown as formula VII with hydrogen to obtain the chiral tetralone compound shown as the formula VI. The method has the advantages of easy synthesis of raw materials, mild reaction conditions, simple operation, high stereoselectivity and the like, the ee value of the product is up to 92%, and the yield is up to 99%.
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Paragraph 0126-0131
(2021/04/26)
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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.
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Paragraph 0092-0100
(2021/09/08)
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- Pickering-Droplet-Derived MOF Microreactors for Continuous-Flow Biocatalysis with Size Selectivity
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Enzymatic microarchitectures with spatially controlled reactivity, engineered molecular sieving ability, favorable interior environment, and industrial productivity show great potential in synthetic protocellular systems and practical biotechnology, but their construction remains a significant challenge. Here, we proposed a Pickering emulsion interface-directed synthesis method to fabricate such a microreactor, in which a robust and defect-free MOF layer was grown around silica emulsifier stabilized droplet surfaces. The compartmentalized interior droplets can provide a biomimetic microenvironment to host free enzymes, while the outer MOF layer secludes active species from the surroundings and endows the microreactor with size-selective permeability. Impressively, the thus-designed enzymatic microreactor exhibited excellent size selectivity and long-term stability, as demonstrated by a 1000 h continuous-flow reaction, while affording completely equal enantioselectivities to the free enzyme counterpart. Moreover, the catalytic efficiency of such enzymatic microreactors was conveniently regulated through engineering of the type or thickness of the outer MOF layer or interior environments for the enzymes, highlighting their superior customized specialties. This study provides new opportunities in designing MOF-based artificial cellular microreactors for practical applications.
- Liang, Linfeng,Shi, Hu,Tian, Danping,Wang, Jun-Hao,Xue, Nan,Yang, Hengquan,Zhang, Xiaoming
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supporting information
p. 16641 - 16652
(2021/10/20)
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- Impact of the Difluoromethylene Group in the Organocatalyzed Acylative Kinetic Resolution of α,α-Difluorohydrins
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Due to the omnipresence of chiral organofluorine compounds in pharmaceutical, agrochemical, and material chemistry, the development of enantioselective methods for their preparation is highly desirable. In the present study, the enantioselective organocatalyzed acylation of α,α-difluorohydrins using a commercially available chiral isothiourea is reported through a kinetic resolution (KR) process. It reveals that the difluoromethylene moiety (C(sp3)F2) can serve as a directing group through electrostatic fluorine–cation interactions, greatly improving the enantioselectivity of the KR. In this context, a broad range of fluorinated alcohols such as valuable 4,4-difluoro-1,3-diols could be synthesized with exquisite enantiocontrol (typically >99:1 er). Turning to 2,2-difluoro-1,3-diols, we also demonstrated that aromatic and fluorinated groups were mutually compatible to provide the expected enantioenriched adducts with >99:1 er.
- Andrei, Daniela,Bressy, Cyril,Desrues, Titouan,Médebielle, Maurice,Merad, Jérémy,Parrain, Jean-Luc,Pons, Jean-Marc,Quintard, Adrien
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supporting information
p. 24924 - 24929
(2021/10/19)
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- Ni/Chiral Sodium Carboxylate Dual Catalyzed Asymmetric O-Propargylation
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A highly enantioselective O-propargylation catalyzed by combining a phosphine-nickel complex and an axially chiral sodium dicarboxylate has been developed. The transformation features mild reaction conditions, a broad substrate scope, and excellent functional group tolerance, offering an efficient approach to an array of enantioenriched O-propargyl hydroxylamines. Mechanistic studies support the presumed role of the chiral carboxylate as a counterion for nickel catalysis enabling the discovery of highly stereoselective transformations. The power of this reaction is illustrated by its application in the asymmetric total synthesis of potent firefly luciferase inhibitors and (S)-dihydroyashabushiketol.
- Chang, Xihao,Guo, Chang,Peng, Lingzi,Xu, Xianghong
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p. 21048 - 21055
(2021/12/14)
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- Cu-catalyzed cross-coupling of benzylboronic esters and epoxides
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A reaction between epoxides and benzylboronic acid pinacol esters is described. CuI was found to be an effective catalyst of this transformation upon activation of the benzylboronic ester with an alkyllithium reagent. The reaction was very efficient and a variety of substituted epoxides were found to be good substrates with good regioselectivity for substitution at the less substituted side of the epoxide. A reaction using an enantioenriched secondary benzylboronic ester was found to not be stereospecific.
- Gierszal, Sophia G.,Barker, Timothy J.
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supporting information
(2021/09/20)
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- Stereospecific Nickel-Catalyzed Reductive Cross-Coupling of Alkyl Tosylate and Allyl Alcohol Electrophiles
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The stereospecific cross-coupling of easily accessed electrophiles holds significant promise in the construction of C-C bonds. Herein, we report a nickel-catalyzed reductive coupling of allyl alcohols with chiral, nonracemic alkyl tosylates. This cross-coupling delivers valuable allylation products with high levels of stereospecificity across a range of substrates. The catalytic system consists of a simple nickel salt in conjunction with a commercially available reductant and importantly represents a rare example of a cross-coupling involving the C-O bonds of two electrophiles.
- Alexanian, Erik J.,Tercenio, Quentin D.
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supporting information
p. 7215 - 7219
(2021/09/22)
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- Deracemization and Stereoinversion of Alcohols Using Two Mutants of Secondary Alcohol Dehydrogenase from Thermoanaerobacter pseudoethanolicus
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We developed a one-pot sequential two-step deracemization approach to chiral alcohols using two mutants of Thermoanaerobacter pseudoethanolicus secondary alcohol dehydrogenase (TeSADH). This approach relies on consecutive non-stereospecific oxidation of alcohols and stereoselective reduction of their prochiral ketones using two mutants of TeSADH with poor and good stereoselectivities, respectively. More specifically, W110G TeSADH enables a non-stereospecific oxidation of alcohol racemates to their corresponding prochiral ketones, followed by W110V TeSADH-catalyzed stereoselective reduction of the resultant ketone intermediates to enantiopure (S)-configured alcohols in up to > 99 percent enantiomeric excess. A heat treatment after the oxidation step was required to avoid the interference of the marginally stereoselective W110G TeSADH in the reduction step; this heat treatment was eliminated by using sol-gel encapsulated W110G TeSADH in the oxidation step. Moreover, this bi-enzymatic approach was implemented in the stereoinversion of (R)-configured alcohols, and (S)-configured alcohols with up to > 99 percent enantiomeric excess were obtained by this Mitsunobu-like stereoinversion reaction.
- Hamdan, Samir M.,Musa, Musa M.,Nafiu, Sodiq A.,Takahashi, Etsuko,Takahashi, Masateru
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- A Simple Biosystem for the High-Yielding Cascade Conversion of Racemic Alcohols to Enantiopure Amines
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The amination of racemic alcohols to produce enantiopure amines is an important green chemistry reaction for pharmaceutical manufacturing, requiring simple and efficient solutions. Herein, we report the development of a cascade biotransformation to aminate racemic alcohols. This cascade utilizes an ambidextrous alcohol dehydrogenase (ADH) to oxidize a racemic alcohol, an enantioselective transaminase (TA) to convert the ketone intermediate to chiral amine, and isopropylamine to recycle PMP and NAD+ cofactors via the reversed cascade reactions. The concept was proven by using an ambidextrous CpSADH-W286A engineered from (S)-enantioselective CpSADH as the first example of evolving ambidextrous ADHs, an enantioselective BmTA, and isopropylamine. A biosystem containing isopropylamine and E. coli (CpSADH-W286A/BmTA) expressing the two enzymes was developed for the amination of racemic alcohols to produce eight useful and high-value (S)-amines in 72–99 % yield and 98–99 % ee, providing with a simple and practical solution to this type of reaction.
- Li, Zhi,Tian, Kaiyuan
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supporting information
p. 21745 - 21751
(2020/09/21)
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- Production of enantiomerically enriched chiral carbinols using whole-cell biocatalyst
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Biocatalytic asymmetric reduction of ketone is an efficient method for the production of chiral carbinols. The study indicates selective bioreduction of different ketones (1–8) to their respective (R)-alcohols (1a–8a) in low to high selectivity (0- >99%) with good yields (11–96%). In this work, whole-cell of Lactobacillus kefiri P2 catalysed enantioselective reduction of various prochiral ketones was investigated. (R)-4-Phenyl-2-butanol 2a, which is used as a precursor to antihypertensive agents and spasmolytics (anti-epileptic agents), was obtained using L kefiri P2 in 99% conversion and 91% enantiomeric excess (ee). Moreover, bioreduction of 2-methyl-1-phenylpropan-1-one substrate 8, containing a branched alkyl chain and difficult to asymmetric reduction with chemical catalysts as an enantioselective, to (R)-2-methyl-1-phenylpropan-1-ol (8a) in enantiomerically pure form was carried out in excellent yield (96%). The gram-scale production was carried out, and 9.70 g of (R)-2-methyl-1-phenylpropan-1-ol (8a) in enantiomerically pure form was obtained in 96% yield. Also especially, the yield and gram scale of (R)-2-methyl-1-phenylpropan-1-ol (8a) synthesised through catalytic asymmetric reduction using the biocatalyst was the highest report so far. The efficiency of L kefiri P2 for the conversion of the substrates and ee of products were markedly influenced by the steric factors of the substrates. This is a cheap, clean and eco-friendly process for production of chiral carbinols compared to chemical processes.
- ?ahin, Engin,Bayda?, Yasemin,Kalay, Erbay
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- Boron containing chiral Schiff bases: Synthesis and catalytic activity in asymmetric transfer hydrogenation (ATH) of ketones
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Asymmetric Transfer Hydrogenation (ATH) has been an attractive way for the reduction of ketones to chiral alcohols. A great number of novel and valuable synthetic pathways have been achived by the combination usage of organometallic and coordination chemistry for the production of important class of compounds and particularly optically active molecules. For this aim, four boron containing Schiff bases were synthesized by the reaction of 4-formylphenylboronic acid with chiral amines. The boron containing structures have been found as stable compounds due to the presence of covalent B–O bonds and thus could be handled in laboratory environment. They were characterized by 1H NMR and FT-IR spectroscopy and elemental analysis and they were used as catalyst in the transfer hydrogenation of ketones to the related alcohol derivatives with high conversions (up to 99%) and low enantioselectivities (up to 22% ee).
- Pa?a, Salih,Arslan, Nevin,Meri??, Nermin,Kayan, Cezmi,Bingül, Murat,Durap, Feyyaz,Aydemir, Murat
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- Enantioselective transfer hydrogenation of pro-chiral ketones catalyzed by novel ruthenium and iridium complexes of well-designed phosphinite ligand
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The interaction of [Ru(η6-arene)(μ-Cl)Cl]2 and Ir(η5-C5Me5)(μ-Cl)Cl]2 with a new Ionic Liquid-based phosphinite ligand, [(Ph2PO)-C6H9N2Ph]Cl, (2) gave [Ru((Ph2PO)-C6H9N2Ph)(η6-p-cymene)Cl2]Cl (3), [Ru((Ph2PO)-C6H9N2Ph)(benzene)Cl2]Cl (4) and [Ir((Ph2PO)-C6H9N2Ph)(C5Me5)Cl2]Cl (5), complexes. All the compounds were characterized by a combination of multinuclear NMR and IR spectroscopy as well as elemental analysis. Furthermore, the Ru(II) and Ir(III) catalysts were applied to asymmetric transfer hydrogenation of acetophenone derivatives using 2-propanol as a hydrogen source. The results showed that the corresponding alcohols could be obtained with good activity (up to 55% ee and 99% conversion) under mild conditions. Notably, [Ir((Ph2PO)-C6H9N2Ph)(C5Me5)Cl2]Cl (5) is more active than the other analogous complexes in the transfer hydrogenation (up to 81% ee).
- Arslan, Nevin
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p. 628 - 637
(2020/01/02)
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- Chiral Imidazo[1,5- a]pyridine-Oxazolines: A Versatile Family of NHC Ligands for the Highly Enantioselective Hydrosilylation of Ketones
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Herein we report the synthesis and application of a versatile class of N-heterocyclic carbene ligands based on an imidazo[1,5-a]pyridine-3-ylidine backbone that is fused to a chiral oxazoline auxiliary. The key step in the synthesis of these ligands involves the installation of the oxazoline functionality via a microwave-assisted condensation of a cyano-azolium salt with a wide variety of 2-amino alcohols. The resulting chiral bidentate NHC-oxazoline ligands form stable complexes with rhodium(I) that are efficient catalysts for the enantioselective hydrosilylation of structurally diverse ketones. The corresponding secondary alcohols are isolated in good yields (typically >90%) with good to excellent enantioselectivities (80-93% ee). The reported hydrosilylation occurs at ambient temperatures (40 °C), with excellent functional group tolerability. Even ketones bearing heterocyclic substituents (e.g., pyridine or thiophene) or complex organic architectures are hydrosilylated efficiently, which is discussed further in this report.
- Chinna Ayya Swamy,Varenikov, Andrii,Ruiter, Graham De
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supporting information
p. 247 - 257
(2020/02/04)
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- Copper(I) Diphosphine Bifluoride Complexes as Efficient Preactivated Catalysts for Nucleophilic Addition on Unsaturated Functional Groups
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Herein we report the synthesis of a family of copper(I) diphosphine bifluoride complexes, their characterization, and their use as efficient preactivated catalysts for nucleophilic copper addition of pronucleophiles on unsaturations. Their use as mechanistic probes is also highlighted by the identification of two copper deuterides.
- Rasson, Corentin,Riant, Olivier
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supporting information
p. 835 - 840
(2020/02/13)
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- Asymmetric Hydrogenation of Ketones and Enones with Chiral Lewis Base Derived Frustrated Lewis Pairs
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The concept of frustrated Lewis pairs (FLPs) has been widely applied in various research areas, and metal-free hydrogenation undoubtedly belongs to the most significant and successful ones. In the past decade, great efforts have been devoted to the synthesis of chiral boron Lewis acids. In a sharp contrast, chiral Lewis base derived FLPs have rarely been disclosed for the asymmetric hydrogenation. In this work, a novel type of chiral FLP was developed by simple combination of chiral oxazoline Lewis bases with achiral boron Lewis acids, thus providing a promising new direction for the development of chiral FLPs in the future. These chiral FLPs proved to be highly effective for the asymmetric hydrogenation of ketones, enones, and chromones, giving the corresponding products in high yields with up to 95 % ee. Mechanistic studies suggest that the hydrogen transfer to simple ketones likely proceeds in a concerted manner.
- Du, Haifeng,Feng, Xiangqing,Gao, Bochao,Meng, Wei
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supporting information
p. 4498 - 4504
(2020/02/05)
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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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- Asymmetric Catalytic Meerwein-Ponndorf-Verley Reduction of Ketones with Aluminum(III)-VANOL Catalysts
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We report herein an efficient aluminum-catalyzed asymmetric MPV reduction of ketones with broad substrate scope and excellent yields and enantiomeric inductions. A variety of aromatic (both electron-poor and electron-rich) and aliphatic ketones were converted to chiral alcohols in good yields with high enantioselectivities (26 examples, 70-98percent yield and 82-99percent ee). This method operates under mild conditions (-10 °C) and low catalyst loading (1-5 mol percent). Furthermore, this process is catalyzed by the earth-abundant main-group element aluminum and employs 2-propanol as the hydride source.
- Guan, Yong,Mohammadlou, Aliakbar,Staples, Richard,Sullivan, Ryan P.,Wulff, William D.,Yin, Xiaopeng,Zheng, Li
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p. 7188 - 7194
(2020/07/21)
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- P-chirogenic Trost ligands mediated asymmetric hydrogenation of simple ketones
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Herein, we report a highly active catalyst system consisting of (Rc,Rc,Rp,Rp)-P-chirogenic Trost ligand and [Ru(C6H6)Cl2]2 for asymmetric hydrogenation of simple ketones, affording the corresponding optically active alcohols in moderate enantioselectivity. A synergetic effect between P- and C-chirogenic centers of the P-chirogenic Trost ligands was observed in this asymmetric hydrogenation process.
- Du, Peng,Liu, Yan-Lan,Lu, Xiao-Bing
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supporting information
(2020/09/22)
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- Synthesis of cis-1,2-diol-type chiral ligands and their dioxaborinane derivatives: Application for the asymmetric transfer hydrogenation of various ketones and biological evaluation
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Two cis-1,2-diol-type chiral ligands (T1 and T2) and their tri-coordinated chiral dioxaborinane (T(1–2)B(1–2)) and four-coordinated chiral dioxaborinane adducts with 4-tert-butyl pyridine sustained by N → B dati
- Kilic, Ahmet,Balci, Tu?ba Ersayan,Arslan, Nevin,Aydemir, Murat,Durap, Feyyaz,Okumu?, Veysi,Tekin, Recep
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- One-Pot Transformation of Ketoximes into Optically Active Alcohols and Amines by Sequential Action of Laccases and Ketoreductases or ω-Transaminases
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An enzymatic one-pot process for asymmetric transformation of prochiral ketoximes into alcohols or amines was developed by sequential coupling of a laccase-catalyzed deoximation either with a ketone reduction (ketoreductase, KRED) or bioamination (ω-transaminase, ω-TA) in aqueous medium. An accurate selection of biocatalysts provided the corresponding products in excellent enantiomeric excesses and overall conversions ranging from 83 to >99 % for alcohols and 70 to >99 % for amines. Likewise, the employment of exclusively 1 % (w/w) of Cremophor, a polyethoxylated castor oil, as co-solvent enabled to reach concentrations up to 100 mM in the chiral alcohols cascade.
- Correia Cordeiro, Raquel S.,Ríos-Lombardía, Nicolás,Morís, Francisco,Kourist, Robert,González-Sabín, Javier
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p. 1272 - 1277
(2019/01/24)
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- Thermoregulated ionic liquid-coordinating ruthenium complexes for asymmetric hydrogenation of aromatic ketones
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This work presented the synthesis and characterization of new ionic liquid-coordinating ruthenium complexes. The resulting ruthenium complexes exhibited not only excellent thermoregulated phase-separation behavior but also highly catalytic activity and enantioselectivity for the asymmetric hydrogenation with molecular hydrogen. The thermoregulated ionic liquid catalyst was highly resistant to leaching and was recycled consecutively for six times without significant loss of catalytic activity and enantioselectivity. The presence of Ru–H species revealed that NH and a Ru–H unit, involved in the hydride transfer process, were of great importance in the present catalytic system.
- Tang, Guoping,Chen, Manyu,Fang, Jian,Xu, Zichen,Gong, Honghui,Peng, Qingpo,Hou, Zhenshan
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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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- Catalysts for the asymmetric transfer hydrogenation of various ketones from [3-[(2S)-2-[(diphenylphosphanyl)oxy]-3-phenoxypropyl]-1-methyl-1H-imidazol-3-ium chloride] and [Ru(η6-arene)(μ-Cl)Cl]2, Ir(η5-C5Me5)(μ-Cl)Cl]2 or [Rh(μ-Cl)(cod)]2
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The combination of [3-[(2S)-2-[(diphenylphosphanyl)oxy]-3-phenoxypropyl]-1-methyl-1H-imidazol-3-ium chloride] with [Ru(η6-arene)(μ-Cl)Cl]2, Ir(η5-C5Me5)(μ-Cl)Cl]2 or [Rh(μ-Cl)(cod)]2, in the presence of KOH/isoPrOH, has been found to generate catalysts that are capable of enantioselectively reducing alkyl, aryl ketones to the corresponding (R)-alcohols. Under optimized conditions, when the catalysts were applied to the asymmetric transfer hydrogenation, we obtained the secondary alcohol products in high conversions and enantioselectivities using only 0.5 mol% catalyst loading. In addition, [3-[(2S)-2-{[(chloro(?4-1,5-cyclooctadiene)rhodium)diphenyl phosphanyl] oxy}-3-phenoxypropyl]-1-methyl-1H-imidazol-3-ium chloride], (6) complex is much more active than the other analogous complexes in the transfer hydrogenation. Catalyst 6 acts as excellent catalysts, giving the corresponding (R)-1-phenyl ethanol in 99% conversion in 30 min (TOF ≤ 396 h?1) and in high enantioselectivity (92% ee).
- Meri?, Nermin,Arslan, Nevin,Kayan, Cezmi,Rafikova, Khadichakhan,Zazybin, Alexey,Kerimkulova, Aygul,Aydemir, Murat
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p. 108 - 118
(2019/04/17)
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- Cooperative Catalysis of an Alcohol Dehydrogenase and Rhodium-Modified Periodic Mesoporous Organosilica
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The combined use of a metal-complex catalyst and an enzyme is attractive, but typically results in mutual inactivation. A rhodium (Rh) complex immobilized in a bipyridine-based periodic mesoporous organosilica (BPy-PMO) shows high catalytic activity during transfer hydrogenation, even in the presence of bovine serum albumin (BSA), while a homogeneous Rh complex exhibits reduced activity due to direct interaction with BSA. The use of a smaller protein or an amino acid revealed a clear size-sieving effect of the BPy-PMO that protected the Rh catalyst from direct interactions. A combination of Rh-immobilized BPy-PMO and an enzyme (horse liver alcohol dehydrogenase; HLADH) promoted sequential reactions involving the transfer hydrogenation of NAD+ to give NADH followed by the asymmetric hydrogenation of 4-phenyl-2-butanone with high enantioselectivity. The use of BPy-PMO as a support for metal complexes could be applied to other systems consisting of a metal-complex catalyst and an enzyme.
- Himiyama, Tomoki,Waki, Minoru,Maegawa, Yoshifumi,Inagaki, Shinji
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supporting information
p. 9150 - 9154
(2019/07/16)
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- Pickering Emulsion-Derived Liquid-Solid Hybrid Catalyst for Bridging Homogeneous and Heterogeneous Catalysis
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We describe a novel method to prepare a liquid-solid hybrid catalyst via interfacial growth of a porous silica crust around Pickering emulsion droplets, which allowed us to overcome the current limitations of both homogeneous and heterogeneous catalysts. The inner micron-scaled liquid (for example, ionic liquids) pool of the resultant catalyst can host free homogeneous molecular catalysts or enzymes to create a true homogeneous catalysis environment. The porous silica crust of the hybrid catalyst has excellent stability, which makes it amenable to packing directly in fixed-bed reactors for continuous flow catalysis. As a proof of concept, the enzymatic kinetic resolution of racemic alcohols, CrIII(salen) complex-catalyzed asymmetric ring opening of epoxides and Pd-catalyzed Tsuji-Trost allylic substitution reactions were used to verify the generality and versatility of our strategy for bridging homogeneous and heterogeneous catalysis. The hybrid catalyst-based continuous flow system exhibited a 1.6a16-fold enhancement in activity relative to homogeneous counterparts even over 1500 h, and the afforded enantioselectivities were completely equal to those obtained in the homogeneous counterpart systems. Interestingly, the catalytic efficiency can be tuned through rational engineering of the porous crust and the dimensions of the liquid pool, resulting in features of an innovatively designed catalyst. This contribution provides a new method to design efficient catalysts that can bridge the conceptual and technical gaps between homogeneous and heterogeneous catalysis.
- Zhang, Xiaoming,Hou, Yiting,Ettelaie, Rammile,Guan, Ruqun,Zhang, Ming,Zhang, Yabin,Yang, Hengquan
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supporting information
p. 5220 - 5230
(2019/03/11)
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- Enantioselective Reduction of α,β-Unsaturated Ketones and Aryl Ketones by Perakine Reductase
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This report describes the enantioselective reduction of structurally diverse α,β-unsaturated ketones and aryl ketones by perakine reductase (PR) from Rauvolfia. This enzymatic reduction produces α-chiral allylic and aryl alcohols with excellent enantioselectivity and most of the products in satisfactory yields. Furthermore, the work demonstrates 1 mmol scale reactions for product delivery without any detrimental effect on yield and enantioselectivity. The catalytic mechanism, determined by 3D-structure-based modeling of PR and ligand complexes, is also described.
- Cai, Sheng,Shao, Nana,Chen, Yuanyuan,Li, Anbang,Pan, Jie,Zhu, Huajian,Zou, Hongbin,Zeng, Su,Sun, Lianli,Zhao, Jinhao
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supporting information
p. 4411 - 4414
(2019/05/22)
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- Cobalt-Catalyzed Aminocarbonylation of Alkyl Tosylates: Stereospecific Synthesis of Amides
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Metal-catalyzed aminocarbonylation is a standard approach for installing amide functionality in chemical synthesis. Despite broad application of this transformation using aryl or vinyl electrophiles, there are few examples involving unactivated aliphatic substrates. Furthermore, there are no stereocontrolled aminocarbonylations of alkyl electrophiles known. Herein, we report a stereospecific aminocarbonylation of unactivated alkyl tosylates for the synthesis of enantioenriched amides. This cobalt-catalyzed transformation uses a remarkably broad range of amines and proceeds with excellent stereospecificity and chemoselectivity.
- Sargent, Brendon T.,Alexanian, Erik J.
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supporting information
p. 9533 - 9536
(2019/06/24)
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- Manganese-Catalyzed Stereospecific Hydroxymethylation of Alkyl Tosylates
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The development of a stereospecific hydroxymethylation of alkyl tosylates using an inexpensive, first-row catalyst is described. The transformation proceeds under mild conditions with low pressure to deliver homologated alcohols as products. Chiral, nonracemic β-branched primary alcohols are obtained with high enantiospecificity from easily accessed secondary alkyl substrates. Simple modification of the reaction system also permits access to α-d2 alcohols. These studies use anionic metal carbonyl catalysis to access a synthetic equivalent of the challenging hydroxymethyl anion from carbon monoxide.
- Shenouda, Hannah,Alexanian, Erik J.
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supporting information
p. 9268 - 9271
(2019/11/19)
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- Asymmetric Enzymatic Hydration of Unactivated, Aliphatic Alkenes
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The direct enantioselective addition of water to unactivated alkenes could simplify the synthesis of chiral alcohols and solve a long-standing challenge in catalysis. Here we report that an engineered fatty acid hydratase can catalyze the asymmetric hydration of various terminal and internal alkenes. In the presence of a carboxylic acid decoy molecule for activation of the oleate hydratase from E. meningoseptica, asymmetric hydration of unactivated alkenes was achieved with up to 93 % conversion, excellent selectivity (>99 % ee, >95 % regioselectivity), and on a preparative scale.
- Demming, Rebecca M.,Hammer, Stephan C.,Nestl, Bettina M.,Gergel, Sebastian,Fademrecht, Silvia,Pleiss, Jürgen,Hauer, Bernhard
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supporting information
p. 173 - 177
(2018/12/11)
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- Biocatalytic Racemization Employing TeSADH: Substrate Scope and Organic Solvent Compatibility for Dynamic Kinetic Resolution
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Racemization in combination with a kinetic resolution is the base for a dynamic kinetic resolution (DKR). Biocatalytic racemization was successfully performed for a broad scope of sec-alcohols by employing a single alcohol dehydrogenase (ADH) variant from Thermoanaerobacter pseudoethanolicus (formerly T. ethanolicus; TeSADH W110A I86A C295A). The catalyst employed as a lyophilized whole cell preparation or cell free extract, which tolerated various non-water miscible organic solvents under micro-aqueous or two-phase conditions, whereby cyclohexane and n-hexane suited best. Various concepts for combining the enzymatic racemization with an enzymatic kinetic resolution to achieve overall a bis-enzymatic DKR were evaluated. A proof of concept showed a successful DKR with racemization in aqueous phase combined with acylation in the organic phase.
- Pop?oński, Jaros?aw,Reiter, Tamara,Kroutil, Wolfgang
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p. 763 - 768
(2018/02/27)
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- A new class of well-defined ruthenium catalysts for enantioselective transfer hydrogenation of various ketones
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A pair of novel optically pure phosphinite ligands were synthesized by ring opening reaction of chiral amines with (R)-styrene oxide or (S)-glycidyl phenyl ether oxide using a straightforward method in high yields and their ruthenium complexes were described in detail. The ruthenium complexes proved to be highly efficient catalysts for the enantioselective hydrogenation of ketones, affording products up to 99% ee. The results showed that the corresponding chiral alcohols could be obtained with high activity and excellent enantioselectivities at the desired temperature. (2S)-1-{benzyl[(1S)-1-(naphthalen-1-yl)ethyl]amino}-3-phenoxypropan-2-yl diphenylphosphinito[dichloro(η6-benzene)ruthenium (II)] acts an excellent catalyst in the reduction of ketones, giving the corresponding alcohol up to 99% ee.
- Kayan, Cezmi,Meri?, Nermin,Rafikova, Khadichakhan,Zazybin, Alexey,Gürbüz, Nevin,Karakaplan, Mehmet,Aydemir, Murat
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- Programming cascade reactions interfacing biocatalysis with transition-metal catalysis in: Deep Eutectic Solvents as biorenewable reaction media
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The first application of Deep Eutectic Solvents (DESs) in the asymmetric bioreduction of ketones has been accomplished for purified ketoreductases (KREDs). The performance of the biocatalysts was enhanced by increasing the percentage of neoteric solvent in DES-buffer mixtures. At a buffer content of 50% (w/w) and even 20% (w/w), the combination of either choline chloride (ChCl)/glycerol (Gly) (1:2) or ChCl/sorbitol (1:1) proved to be most effective for achieving up to >99% conversion and up to >99% enantiomeric excess of the corresponding secondary alcohols. Moreover, this reaction medium was used to perform the first example of a chemoenzymatic cascade process in DES-buffer mixtures, namely the ruthenium-catalysed isomerisation of racemic allylic alcohols coupled with a further enantioselective bioreduction, in both sequential and concurrent modes.
- Cicco, Luciana,Ríos-Lombardía, Nicolás,Rodríguez-álvarez, María J.,Morís, Francisco,Perna, Filippo M.,Capriati, Vito,García-álvarez, Joaquín,González-Sabín, Javier
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supporting information
p. 3468 - 3475
(2018/08/07)
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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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- Chiral C2-symmetric η6-p-cymene-Ru(II)-phosphinite complexes: Synthesis and catalytic activity in asymmetric reduction of aromatic, methyl alkyl and alkyl/aryl ketones
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Chiral C2-symmetric bis(phosphinite) ligands and their binuclear ruthenium(II) complexes have been synthesized and used as catalysts in the ruthenium-catalyzed asymmetric transfer hydrogenation of aromatic, methyl alkyl and alkyl/aryl ketones using 2-propanol as both the hydrogen source and solvent in the presence of KOH. Under optimized conditions, all complexes showed high catalytic activity as catalysts in the reduction of various ketones to corresponding chiral secondary alcohols. Products were obtained with high conversions (99%) and moderate to good enantioselectivities (82% ee). Furthermore, C2-symmetric bis(phosphinite) ligands and their binuclear ruthenium(II) complexes were characterized by multinuclear NMR spectroscopy, FT-IR spectroscopy, LC/MS-MS and elemental analysis.
- Karaka?, Duygu Elma,Aydemir, Murat,Durap, Feyyaz,Baysal, Ak?n
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p. 430 - 439
(2017/12/06)
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- Methodology Development in Directed Evolution: Exploring Options when Applying Triple-Code Saturation Mutagenesis
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Directed evolution of stereo- or regioselective enzymes as catalysts in asymmetric transformations is of particular interest in organic synthesis. Upon evolving these biocatalysts, screening is the bottleneck. To beat the numbers problem most effectively, methods and strategies for building “small but smart” mutant libraries have been developed. Herein, we compared two different strategies regarding the application of triple-code saturation mutagenesis (TCSM) at multiresidue sites of the Thermoanaerobacter brockii alcohol dehydrogenase by using distinct reduced amino-acid alphabets. By using the synthetically difficult-to-reduce prochiral ketone tetrahydrofuran-3-one as a substrate, highly R- and S-selective variants were obtained (92–99 % ee) with minimal screening. The origin of stereoselectivity was provided by molecular dynamics analyses, which is discussed in terms of the Bürgi–Dunitz trajectory.
- Qu, Ge,Lonsdale, Richard,Yao, Peiyuan,Li, Guangyue,Liu, Beibei,Reetz, Manfred T.,Sun, Zhoutong
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p. 239 - 246
(2018/02/09)
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- Enantioselective metal-free reduction of ketones by a user-friendly silane with a reusable chiral additive
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1-Hydrosilatrane, a safe and easy-to-handle reducing reagent that can be inexpensively accessed, has been shown to reduce prochiral ketones asymmetrically in the presence of chiral 1,2-aminoalcohols with ees ranging from 8% to 86%. The best result was achieved using ephedrine as the source of chirality, which is readily commercially available. The additive can be recovered through extraction and reused without any erosion of enantioselectivity.
- Varjosaari, Sami E.,Skrypai, Vladislav,Herlugson, Sharon M.,Gilbert, Thomas M.,Adler, Marc J.
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supporting information
p. 2839 - 2843
(2018/06/25)
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- CHIRAL METAL COMPLEX COMPOUNDS
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The invention comprises novel chiral metal complex compounds of the formula (I) wherein M, PR2, R3 and R4 are outlined in the description, its stereoisomers, in the form as a neutral complex or a complex cation with a suitable counter ion. The chiral metal complex compounds can be used in asymmetric reactions, particularly in asymmetric reductions of ketones, imines or oximes.
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Page/Page column 24; 28
(2018/11/10)
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- Investigation of the Deprotonative Generation and Borylation of Diamine-Ligated α-Lithiated Carbamates and Benzoates by in Situ IR spectroscopy
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Diamine-mediated α-deprotonation of O-alkyl carbamates or benzoates with alkyllithium reagents, trapping of the carbanion with organoboron compounds, and 1,2-metalate rearrangement of the resulting boronate complex are the primary steps by which organoboron compounds can be stereoselectively homologated. Although the final step can be easily monitored by 11B NMR spectroscopy, the first two steps, which are typically carried out at cryogenic temperatures, are less well understood owing to the requirement for specialized analytical techniques. Investigation of these steps by in situ IR spectroscopy has provided invaluable data for optimizing the homologation reactions of organoboron compounds. Although the deprotonation of benzoates in noncoordinating solvents is faster than that in ethereal solvents, the deprotonation of carbamates shows the opposite trend, a difference that has its origin in the propensity of carbamates to form inactive parasitic complexes with the diamine-ligated alkyllithium reagent. Borylation of bulky diamine-ligated lithiated species in toluene is extremely slow, owing to the requirement for initial complexation of the oxygen atoms of the diol ligand on boron with the lithium ion prior to boron-lithium exchange. However, ethereal solvent, or very small amounts of THF, facilitate precomplexation through initial displacement of the bulky diamines coordinated to the lithium ion. Comparison of the carbonyl stretching frequencies of boronates derived from pinacol boronic esters with those derived from trialkylboranes suggests that the displaced lithium ion is residing on the pinacol oxygen atoms and the benzoate/carbamate carbonyl group, respectively, explaining, at least in part, the faster 1,2-metalate rearrangements of boronates derived from the trialkylboranes.
- Mykura, Rory C.,Veth, Simon,Varela, Ana,Dewis, Lydia,Farndon, Joshua J.,Myers, Eddie L.,Aggarwal, Varinder K.
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supporting information
p. 14677 - 14686
(2018/11/20)
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- Expanding the Substrate Specificity of Thermoanaerobacter pseudoethanolicus Secondary Alcohol Dehydrogenase by a Dual Site Mutation
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Here, we report the asymmetric reduction of selected phenyl-ring-containing ketones by various single- and dual-site mutants of Thermoanaerobacter pseudoethanolicus secondary alcohol dehydrogenase (TeSADH). The further expansion of the size of the substrate binding pocket in the mutant W110A/I86A not only allowed the accommodation of substrates of the single mutants W110A and I86A within the expanded active site but also expanded the substrate range of the enzyme to ketones bearing two sterically demanding groups (bulky–bulky ketones), which are not substrates for the TeSADH single mutants. We also report the regio- and enantioselective reduction of diketones with W110A/I86A TeSADH and single TeSADH mutants. The double mutant exhibited dual stereopreference to generate the Prelog products most of the time and the anti-Prelog products in a few cases.
- Musa, Musa M.,Bsharat, Odey,Karume, Ibrahim,Vieille, Claire,Takahashi, Masateru,Hamdan, Samir M.
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p. 798 - 805
(2018/02/21)
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- Biocatalyst-artificial metalloenzyme cascade based on alcohol dehydrogenase
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Chemo-enzymatic cascades of enzymes with transition metal catalysts can offer efficient synthetic strategies, but their development is challenging due to the incompatibility between proteins and transition metal complexes. Rhodium catalysts can be combined with alcohol dehydrogenases to regenerate nicotinamide cofactors using formate as the hydride donor. However, their use is limited, due to binding of the metals to residues on the enzyme surface, leading to mutual enzyme and catalyst inactivation. In this work, we replaced the zinc from Thermoanaerobacter brockii alcohol dehydrogenase (TbADH) with Rh(iii) catalysts possessing nitrogen donor ligands, by covalent conjugation to the active site cysteine, to create artificial metalloenzymes for NADP+ reduction. TbADH was used as protein scaffold for both alcohol synthesis and the recycling of the cofactor, by combination of the chemically modified species with the non-modified recombinant enzyme. Stability studies revealed that the incorporation of the catalysts into the TbADH pocket provided a shielding environment for the metal catalyst, resulting in increased stability of both the recycling catalyst and the ADH. The reduction of a representative ketone using this novel alcohol dehydrogenase-artificial formate dehydrogenase cascade yielded better conversions than in the presence of free metal catalyst.
- Morra, Simone,Pordea, Anca
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p. 7447 - 7454
(2018/10/21)
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- Co-immobilized Whole Cells with ω-Transaminase and Ketoreductase Activities for Continuous-Flow Cascade Reactions
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An improved sol–gel process involving the use of hollow silica microspheres as a supporting additive was applied for the co-immobilization of whole cells of Escherichia coli with Chromobacterium violaceum ω-transaminase activity and Lodderomyces elongisporus with ketoreductase activity. The co-immobilized cells with two different biocatalytic activities could perform a cascade of reactions to convert racemic 4-phenylbutan-2-amine or heptan-2-amine into a nearly equimolar mixture of the corresponding enantiomerically pure R amine and S alcohol even in continuous-flow mode. The novel co-immobilized whole-cell system proved to be an easy-to-store and durable biocatalyst.
- Nagy-Gy?r, László,Abaházi, Emese,Bódai, Viktória,Sátorhelyi, Péter,Erdélyi, Balázs,Balogh-Weiser, Diána,Paizs, Csaba,Hornyánszky, Gábor,Poppe, László
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p. 1845 - 1848
(2018/09/10)
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- Structurally diverse glycoconjugated volatile compounds from Oxytropis falcata Bunge
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A phytochemical investigation on the whole plant of Oxytropis falcata Bunge yielded 16 glycoconjugated compounds with structurally diverse volatile aglycones but similar sugars. Of these, five were previously undescribed compounds with different volatile aglycones but same glucuronic acid (1 → 2) glucosyl moiety, including three octanol glucuronic acid (1 → 2) glucosides (1–3), one acyclic monoterpenoid glucuronic acid (1 → 2) glucoside (4), and one 4-phenyl-butan-2-ol glucuronic acid (1 → 2) glucoside (5), and 11 were biological related known glucoconjugated volatile compounds (6–16) isolated from genus Oxytropis for the first time. The structures of these compounds were determined by extensive spectroscopic analysis of MS, 1D and 2D NMR data. The absolute configurations of aglycones and sugar residues were assigned via enzymatic hydrolysis and subsequently comparison of the specific rotations. This is the first report of such structurally diverse glycoconjugated volatile compounds from O. falcata, which might be regarded as the precursor of free volatile compounds, and presents scientific evidences for better clarifying the volatile compositions of this medicinal plant and genus Oxytropis.
- Wang, Shanshan,Zhang, Xiaojing,Que, Sheng,Liang, Hong,Tu, Pengfei,Zhang, Qingying
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p. 143 - 147
(2018/07/29)
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- Iridium and Rhodium Complexes Containing Enantiopure Primary Amine-Tethered N-Heterocyclic Carbenes: Synthesis, Characterization, Reactivity, and Catalytic Asymmetric Hydrogenation of Ketones
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The imidazolium salt [(S,S)-tBuNC3H3NCHPhCHPhNH2]PF6, (S,S)-11·HPF6 is a precursor to the enantiopure "Kaibene" ligand, tBu-Kaibene, (S,S)-11 featuring a tert-butyl group on the N-heterocyclic carbene (NHC) ring-nitrogen atoms. It has been prepared in high yield and purity by refluxing a chiral cyclic sulfamidate with 1-tert-butylimidazole. Similarly (S,S)-12·HPF6 with a mesityl group at the imidazolium ring-nitrogen atom has been prepared in the same fashion and serves as a source of Mes-Kaibene, (S,S)-12. These bidentate Kaibene ligands feature an NHC and a primary amine separated by a chiral linker. Salts (S,S)-11·HPF6 or (S,S)-12·HPF6 react with base and AgI or CuI to give a total of four M(Kaibene)2I compounds (M = Ag or Cu). At 22 °C, the amine-functionalized imidazolium cations undergo oxidative addition to iridium(I) in [IrCl(cod)]2 (cod = 1,5-cyclooctadiene) to generate iridium(III) hydride R-Kaibene compounds [IrHCl(cod)((S,S)-11)](PF6) (17) and [IrHCl(cod)((S,S)-12)](PF6) (18), respectively, each as a mixture of six configurational isomers. In contrast, the salt (S,S)-11·HPF6 reacts with [Ir(OtBu)(cod)]2 to produce a bimetallic iridium compound with (S,S)-11 as the bridging ligand. This compound contains interesting NH···Cl and NH···Ir noncovalent intramolecular interactions. Salt (S,S)-12·HPF6 reacts with silver oxide to yield [Ag2((S,S)-12)2](PF6)2 (20). Reagent 20 serves as an efficient transmetalation reagent to deliver to each rhodium in [RhCl(cod)]2 1 equiv of (S,S)-12 as a bidentate ligand to give [Rh(cod)((S,S)-12)](PF6). In the reaction between [IrCl(cod)]2 and 20, (S,S)-12 ends up coordinated in an iridium(III) hydride complex (22) as a tridentate ligand via the NHC, NH2, and a cyclometalated phenyl group. The two iridium hydride compounds, 18 and 22, are catalysts for the hydrogenation of a range of ketones (turnover number up to 499, turnover frequency up to 249 h-1, with er (enantiomeric ratio) up to 35:65 R:S).
- Wan, Kai Y.,Roelfes, Florian,Lough, Alan J.,Hahn, F. Ekkehardt,Morris, Robert H.
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supporting information
p. 491 - 504
(2018/02/17)
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- Copper-Catalyzed Enantioselective Markovnikov Protoboration of α-Olefins Enabled by a Buttressed N-Heterocyclic Carbene Ligand
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Reported is a highly enantioselective copper-catalyzed Markovnikov protoboration of unactivated terminal alkenes. A variety of simple and abundant feedstock α-olefins bearing a diverse array of functional groups and heterocyclic substituents can be used as substrates, and the reaction proceeds under mild reaction conditions at ambient temperature to provide expedient access to enantioenriched alkylboronic esters in good regioselectivity and with excellent enantiocontrol. Critical to the success of the protocol was the development and application of a novel, sterically hindered N-heterocyclic carbene, (R,R,R,R)-ANIPE, as the ligand for copper.
- Cai, Yuan,Yang, Xin-Tuo,Zhang, Shuo-Qing,Li, Feng,Li, Yu-Qing,Ruan, Lin-Xin,Hong, Xin,Shi, Shi-Liang
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supporting information
p. 1376 - 1380
(2018/01/27)
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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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