- Palladium catalysed mono-N-arylation of enantiopure diamines
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The palladium catalysed arylation of amines is employed to prepare selectively a range of new, mono-N-arylated, enantiopure diamine ligands. The ligands were tested in the catalytic asymmetric transfer hydrogenation of acetophenone.
- Frost, Christopher G.,Mendonca, Paul
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- Scale-up of a chiral resolution using cross-linked enzyme crystals
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The scale-up of a biocatalytic process using a cross-linked enzyme crystal (ChiroCLEC-PC, Altus Biologics Inc., Cambridge, MA) for the resolution of a racemic mixture (R/S-sec-phenethyl acetate to R-sec-phenethyl alcohol) is reported. Reaction parameters were initially investigated at the 20-mL and 1-L scale to determine optimum reactor conditions for operation at the 100-L scale. At this scale, reproducibility trials were conducted with a single charge of 50 g of ChiroCLEC-PC for the entire nine trials. Results demonstrated that, although there was a steady decrease in reaction rate over the trials (primarily as a result of sub-optimal CLEC catalyst recovery between each trial) all nine reactions proceeded to >48% conversion, with eep's of 99.9% and ees's of 91-95% recorded. In total, 270 kg of racemate was converted into R-phenethyl alcohol and S-phenethyl acetate during the reproducibility trials using a standard stirred tank design with pH control. With further work to improve CLEC catalyst recovery between runs, the technology is suitable for industrial exploitation to compete favourably alongside alternative chiral technologies.
- Collins, Anne M.,Maslin, Christopher,Davies, R. Julian
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- ASYMMETRIC SYNTHESIS XXI. ENANTIOSELECTIVE REDUCTION OF KETONES CATALYZED BY NEW (4S,5R)-4,5-DIPHENYL-1,3,2-OXAZABOROLIDINE
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Oxazaborolidine prepared from (1R,2S)-1,2-diphenyl-2-aminoethanol with borane was used as catalyst in the enantioselective reduction of ketones.Excellent enantioselectivities with e.e. >99percent for acetophenone and e.e. >96percent for ω-bromo-acetophenone have been achieved.
- Yaozhong, Jiang,Yong, Qin,Aiqiao, Mi,Zhitang, Huang
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- Solar-Assisted eBiorefinery: Photoelectrochemical Pairing of Oxyfunctionalization and Hydrogenation Reactions
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Inspired by natural photosynthesis, biocatalytic photoelectrochemical (PEC) platforms are gaining prominence for the conversion of solar energy into useful chemicals by combining redox biocatalysis and photoelectrocatalysis. Herein, we report a dual biocatalytic PEC platform consisting of a molybdenum (Mo)-doped BiVO4 (Mo:BiVO4) photoanode and an inverse opal ITO (IO-ITO) cathode that gives rise to the coupling of peroxygenase and ene-reductase-mediated catalysis, respectively. In the PEC cell, the photoexcited electrons generated from the Mo:BiVO4 are transferred to the IO-ITO and regenerate reduced flavin mononucleotides to drive ene-reductase-catalyzed trans-hydrogenation of ketoisophrone to (R)-levodione. Meanwhile, the photoactivated Mo:BiVO4 evolves H2O2 in situ via a two-electron water-oxidation process with the aid of an applied bias, which simultaneously supplies peroxygenases to drive selective hydroxylation of ethylbenzene into enantiopure (R)-1-phenyl-1-hydroxyethane. Thus, the deliberate integration of PEC systems with redox biocatalytic reactions can simultaneously produce valuable chemicals on both electrodes using solar-powered electrons and water.
- Choi, Da Som,Hollmann, Frank,Kim, Jinhyun,Park, Chan Beum
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- Enantiodivergent asymmetric catalysis with the tropos BIPHEP ligand and a proline derivative as chiral selector
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A catalytic system based on the tropos ligand BIPHEP and (S)-proline methyl ester as chiral selector was studied for Rh-catalysed asymmetric catalysis. By careful control of the catalyst preformation conditions, the enantioselectivity could be completely reversed in asymmetric hydrogenation of prochiral olefins maintaining the same absolute level in favorable cases. The enantiodivergent asymmetric catalysis could be rationalised by the interplay of the dynamic chirality (tropos) of the phosphine ligand and the coordination of the proline selector. Treating a suitable Rh-BIPHEP precursor with the (Sc)-proline-based ionic liquid led to an equimolar mixture of (RaSc)- and (SaSc)-diastereomers that is kinetically stable at 0 °C. At higher temperature, an irreversible diastereomerisation process was observed resulting in the diastereomerically pure (RaSc)-complex [Rh{(Ra)-BIPHEP}{(Sc)-ProlOMe}]. Whereas the use of the pure (RaSc)-complex led to 51% ee (R) in the hydrogenation of methyl 2-acetamidoacrylate, the S-product was formed with almost identical enantioselectivity when the (RaSc)/(SaSc)-mixture was applied under identical conditions. This inversion was associated with the relative stability of the diastereomers in the equilibria forming the catalytically active substrate complex. The possibility to use this different reactivity to control the direction of enantioselectivity was demonstrated for the hydrogenation of different substrates whereby ee's of up to 80% could be achieved. Moreover, the (RaSc)-complex led to high enantioselectivities of up 86% ee in the asymmetric hydroboration of styrene, approaching the performance of the atropos BINAP ligand for this reaction.
- Oczipka,Müller,Leitner,Franciò
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- Covalently Immobilized Lipase on a Thermoresponsive Polymer with an Upper Critical Solution Temperature as an Efficient and Recyclable Asymmetric Catalyst in Aqueous Media
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A thermoresponsive lipase catalyst with an upper critical solution temperature (UCST) of about 26 °C was exploited by covalent immobilization of an enzyme, Pseudomonas cepacia lipase (PSL), onto poly(acrylamide-co-acrylonitrile) by glutaraldehyde coupling. The experimental conditions for the PSL immobilization were optimized. The immobilized PSL was much more stable for wide ranges of temperature and pH than free PSL. The material was also evaluated as an asymmetric catalyst in the kinetic resolution of racemic α-methylbenzyl butyrate at 55 °C in an aqueous medium and exhibited high catalytic performance and stability. Up to 50 % conversion and 99.5 % product enantiomeric excess were achieved, thus providing highly pure enantiomers. This biocatalyst could be easily recovered by simple decantation for reuse based on temperature-induced precipitation. It showed good reusability and retained 80.5 % of its original activity with a well reserved enantioselectivity in the 6th cycle. This work would shed light on the future development of new UCST-type enzyme catalysts.
- Lou, Lan-Lan,Qu, Huaxin,Yu, Wenjun,Wang, Bei,Ouyang, Lezi,Liu, Shuangxi,Zhou, Wuzong
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- Oxazaborolidine Catalyzed Borane Reductions of Ketones: A Significant Effect of Temperature on Selectivity
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The effect of temperature on the selectivity of oxazaborolidine catalyzed borane reductions of ketones has been studied.For two model ketones acetophenone (2a) and cyclohexylmethyl ketone (2b), and two different oxazaborolidine catalysts derived from n-b
- Stone, Guy B.
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- Rapid chiral analysis based on liquid-phase cyclic chemiluminescence
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Rapid chiral analysis has become one of the important aspects of academic and industrial research. Here we describe a new strategy based on liquid-phase cyclic chemiluminescence (CCL) for rapid resolution of enantiomers and determination of enantiomeric excess (ee). A single CCL measurement can acquire multistage signals that provide a unique way to examine the intermolecular interactions between chiral hosts and chiral guests, because the lifetime (τ) of the multistage signals is a concentration-independent and distinguishable constant for a given chiral host-guest system. According to the τ values, CCL allows discrimination between a wide range of enantiomeric pairs including chiral alcohols, amines and acids by using only one chiral host. Even the chiral systems hardly distinguished by nuclear magnetic resonance and fluorescence methods can be distinguished easily by CCL. Additionally, the τ value of a mixture of two enantiomers is equal to the weighted average of each enantiomer, which can be used for the direct determination of ee without the need to separate the chiral mixture and create calibration curves. This is extremely crucial for the cases without readily available enantiomerically pure samples. This strategy was successfully applied to monitoring of the Walden inversion reaction and analysis of chiral drugs. The results were in good agreement with those obtained by high-performance liquid chromatography, indicating the utility of CCL for routine quick ee analysis. Mechanism study revealed that the τ value is possibly related to the activity of the chiral substance to catalyze a luminol-H2O2 reaction. Our research provides an unprecedented and general protocol for chirality differentiation and ee determination, which is anticipated to be a useful technology that will find wide application in chirality-related fields, particularly in asymmetric synthesis and the pharmaceutical industry.
- Zhang, Runkun,Zhong, Yanhui,Lu, Zhenyu,Chen, Yanlong,Li, Gongke
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- Combined microbial oxidation and reduction: A new approach to the high-yield synthesis of homochiral unsaturated secondary alcohols from racemates
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The oxidation of racemic secondary alcohols with Bacillus stearothermophilus followed by reduction of the mixture with Yarrowia lipolytica to afford high yields of the enantiomerically pure R-alcohols 1a,b,d is described. Comparisons with Yarrowia lipolytica reduction, Bacillus stearothermophilus oxidation, and the contemporary use of the two microorganisms have been made.
- Fantin,Fogagnolo,Giovannini,Medici,Pedrini
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- Microscale Atmospheric Pressure Plasma Jet as a Source for Plasma-Driven Biocatalysis
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The use of a microscale atmospheric pressure plasma jet (μAPPJ) was investigated for its potential to supply hydrogen peroxide in biocatalysis. Compared to a previously employed dielectric barrier discharge (DBD), the μAPPJ offered significantly higher H2O2 production rates and better handling of larger reaction volumes. The performance of the μAPPJ was evaluated with recombinant unspecific peroxygenase from Agrocybe aegerita (rAaeUPO). Using plasma-treated buffer, no side reactions with other plasma-generated species were detected. For long-term treatment, rAaeUPO was immobilized, transferred to a rotating bed reactor, and reactions performed using the μAPPJ. The enzyme had a turnover of 36,415 mol mol?1 and retained almost full activity even after prolonged plasma treatment. Overall, the μAPPJ presents a promising plasma source for plasma-driven biocatalysis.
- Yayci, Abdulkadir,Dirks, Tim,Kogelheide, Friederike,Alcalde, Miguel,Hollmann, Frank,Awakowicz, Peter,Bandow, Julia E.
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- Mechanism of Asymmetric Hydrogenation of Aromatic Ketones Catalyzed by a Combined System of Ru(π-CH2C(CH3)CH2)2(cod) and the Chiral sp2N/sp3NH Hybrid Linear N4 Ligand Ph-BINAN-H-Py
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The combination of a Goodwin-Lions-type chiral N4 ligand, (R)-Ph-BINAN-H-Py ((R)-3,3′-diphenyl-N2,N2′-bis((pyridin-2-yl)methyl)-1,1′-binaphthyl-2,2′-diamine; L), with Ru(π-CH2C(CH3)CH2)2(co
- Nakatsuka, Hiroshi,Yamamura, Tomoya,Shuto, Yoshihiro,Tanaka, Shinji,Yoshimura, Masahiro,Kitamura, Masato
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- Dynamic Covalent Chemistry within Biphenyl Scaffolds: Reversible Covalent Bonding, Control of Selectivity, and Chirality Sensing with a Single System
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Axial chirality is a prevalent and important phenomenon in chemistry. Herein we report a combination of dynamic covalent chemistry and axial chirality for the development of a versatile platform for the binding and chirality sensing of multiple classes of mononucleophiles. An equilibrium between an open aldehyde and its cyclic hemiaminal within biphenyl derivatives enabled the dynamic incorporation of a broad range of alcohols, thiols, primary amines, and secondary amines with high efficiency. Selectivity toward different classes of nucleophiles was also achieved by regulating the distinct reactivity of the system with external stimuli. Through induced helicity as a result of central-to-axial chirality transfer, the handedness and ee values of chiral monoalcohol and monoamine analytes were reported by circular dichroism. The strategies introduced herein should find application in many contexts, including assembly, sensing, and labeling.
- Ni, Cailing,Zha, Daijun,Ye, Hebo,Hai, Yu,Zhou, Yuntao,Anslyn, Eric V.,You, Lei
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- Plasma-Driven in Situ Production of Hydrogen Peroxide for Biocatalysis
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Peroxidases and peroxygenases are promising classes of enzymes for biocatalysis because of their ability to carry out one-electron oxidation reactions and stereoselective oxyfunctionalizations. However, industrial application is limited, as the major drawback is the sensitivity toward the required peroxide substrates. Herein, we report a novel biocatalysis approach to circumvent this shortcoming: in situ production of H2O2 by dielectric barrier discharge plasma. The discharge plasma can be controlled to produce hydrogen peroxide at desired rates, yielding desired concentrations. Using horseradish peroxidase, it is demonstrated that hydrogen peroxide produced by plasma treatment can drive the enzymatic oxidation of model substrates. Fungal peroxygenase is then employed to convert ethylbenzene to (R)-1-phenylethanol with an ee of >96 % using plasma-generated hydrogen peroxide. As direct treatment of the reaction solution with plasma results in reduced enzyme activity, the use of plasma-treated liquid and protection strategies are investigated to increase total turnover. Technical plasmas present a noninvasive means to drive peroxide-based biotransformations.
- Alcalde, Miguel,Bandow, Julia E.,Baraibar, álvaro Gómez,Fueyo, Elena Fernandez,Hollmann, Frank,Kourist, Robert,Krewing, Marco,Yayci, Abdulkadir
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- Effects of chemical modification on stereoselectivity of Pseudomonas cepacia lipase
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Two chemically modified forms of lipase from Pseudomonas cepacia were prepared by acylation of the free amino groups of the protein with acetic and succinic anhydrides.The catalytic activity, the enantioselectivity and the thermal stability of the modified enzymes were compared with that of the native form.Succinylation determined an increase of stability without affecting the catalytical properties of the enzyme in the hydrolysis of chiral esters.Acetylation resulted in an enhanced catalytic activity coupled to a decreased stereoselectivity and thermal stability.
- Bianchi, Daniele,Battistel, Ezio,Bosetti, Aldo,Cesti, Pietro,Fekete, Zoltan
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- An immobilized lipase microfluidic reactor for enantioselective hydrolysis of ester
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Enantioselective enzymatic hydrolysis of racemic mixture is an effective method to obtain pure enantiomer. In this report, an immobilized lipase microfluidic reactor was fabricated and applied to enantioselective hydrolysis of racemic 1-phenylethyl acetate to obtain (R)-l-phenylethanol. This immobilized lipase microfluidic reactor consumed trace amount of enzyme, showed identical performance compared to free enzyme in batch, and good stability that can be recycled for at least eight times without obvious loss of activity. Copyright
- Gao, Yan,Zhong, Runtao,Qin, Jianhua,Lin, Bingcheng
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- Development of environmentally friendly lipase-catalysed kinetic resolution of (R,S)-1-phenylethyl acetate using aqueous natural deep eutectic solvents
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Over the past decade, natural deep eutectic solvents (NADES) have become promising green solvent from both environmental and technological perspectives. The number of structural combinations encompassed by NADES is tremendous; thus, NADES with unique physicochemical properties can be designed for a particular purpose, such as for efficient biocatalytic processes. The aim of this work was to prepare several NADES based on renewable sources (biomass energy) and to apply these solvents in the industrially interesting process of lipase-catalysed (R)-1-phenylethanol synthesis. Based on experimental data on lipase behaviour in the tested NADES, choline chloride:glycerol (ChGly) was selected as the most promising solvent for the given reaction. The resulting (R)-1-phenylethanol was also successfully isolated and purified from the reaction mixture using liquid-liquid extraction with ethyl acetate, whilst ChGly was recycled and reused. (R)-1-phenylethanol and unreacted (S)-1-phenylethyl acetate were purified on silica gel columns with yields of 81.91 %. The biocatalyst was also successfully recycled and reused in 4 cycles. Based on laboratory-scale optimum conditions, (R)-1-phenylethanol synthesis performed in a 500 mL batch reactor achieved reaction conversions comparable to those obtained with millilitre-scale biocatalytic reactions. The downstream process was also performed on a preparative scale with a yield of 49.48 %.
- Cvjetko Bubalo, Marina,Jurinjak Tu?ek, Ana,Maros, Izabela,Pani?, Manuela,Radoj?i? Redovnikovi?, Ivana,Radovi?, Mia
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- Cascading g-C3N4 and Peroxygenases for Selective Oxyfunctionalization Reactions
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Peroxygenases are very interesting catalysts for specific oxyfunctionalization chemistry. Instead of relying on complicated electron transport chains, they rely on simple hydrogen peroxide as the stoichiometric oxidant. Their poor robustness against H2O2 can be addressed via in situ generation of H2O2. Here we report that simple graphitic carbon nitride (g-C3N4) is a promising photocatalyst to drive peroxygenase-catalyzed hydroxylation reactions. The system has been characterized by outlining not only its scope but also its current limitations. In particular, spatial separation of the photocatalyst from the enzyme is shown as a solution to circumvent the undesired inactivation of the biocatalyst. Overall, very promising turnover numbers of the biocatalyst of more than 60.000 have been achieved.
- Van Schie, Morten M.C.H.,Zhang, Wuyuan,Tieves, Florian,Choi, Da Som,Park, Chan Beum,Burek, Bastien O.,Bloh, Jonathan Z.,Arends, Isabel W. C. E.,Paul, Caroline E.,Alcalde, Miguel,Hollmann, Frank
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- Highly enantioselective reduction of achiral ketones with NaBH4/Me3SiCl catalyzed by (S)-α,α-diphenylpyrrolidinemethanol
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The reducing agent prepared from sodium borohydride, trimethylsilyl chloride and a catalytic amount of (S)-α,α-diphenylpyrrolidinemethanol has been successfully applied to the enantioselective reduction of ketones. The optically active secondary alcohols were obtained in excellent enantiomeric excess and almost quantitative chemical yield. (C) 2000 Elsevier Science Ltd.
- Jiang, Biao,Feng, Yan,Zheng, Jian
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- Mapping the substrate selectivity and enantioselectivity of esterases from thermophiles
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To identify potential applications of nineteen esterases from thermophiles, we mapped their substrate selectivity and enantioselectivity using a library of 50 esters. We measured the selectivities colorimetrically using Quick E, which uses pH indicators to detect hydrolysis and a chromogenic reference compound as an internal control. The substrate selectivity mapping revealed one esterase, E018b, with a strong preference for acetyl esters (14- to 25-fold over hexanoate). The enantioselectivity mapping revealed a number of cases of high enantioselectivity. Thirteen of the 19 esterases showed moderate or better enantioselectivity (>19) toward 1-phenethyl butyrate favoring the (R)-enantiomer and two esterases (E008, E013) showed moderate or better enantioselectivity (>20) toward methyl 2-chloropropionate favoring the (S)-enantiomer. Three esterases (E001, E004, E005) showed high (>46) enantioselectivity toward menthyl acetate favoring the (R)-enantiomer. This rapid mapping of the selectivity simplifies the characterization of new enzymes.
- Somers, Neil A.,Kazlauskas, Romas J.
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- Photoenzymatic Hydroxylation of Ethylbenzene Catalyzed by Unspecific Peroxygenase: Origin of Enzyme Inactivation and the Impact of Light Intensity and Temperature
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Photoenzymatic cascades can be used for selective oxygenation of C?H-Bonds under mild conditions circumventing the hydrogen peroxide mediated peroxygenase inactivation via in situ H2O2 generation. Here, we report the “on demand” production of hydrogen peroxide via methanol assisted reduction of molecular oxygen using UV-illuminated titanium dioxide (Aeroxide P25) combined with the enantioselective hydroxylation of ethylbenzene to (R)-1-phenylethanole catalyzed by the Unspecific Peroxygenase from Agrocybe Aegerita. For the application of the system it is important to understand the influence of the reaction parameters to be able to optimize the system. Therefore, we systematically investigated product formation and enzyme inactivation as well as ROS formation (H2O2, .OH and .O2?) applying different light intensities and temperatures. As a result, Turnover Numbers up to 220 000, photonic efficiencies up to 13.6 % and production rates up to 0.9 mM h?1 were achieved.
- Burek, Bastien O.,de Boer, Sabrina R.,Tieves, Florian,Zhang, Wuyuan,van Schie, Morten,Bormann, Sebastian,Alcalde, Miguel,Holtmann, Dirk,Hollmann, Frank,Bahnemann, Detlef W.,Bloh, Jonathan Z.
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- New chiral phosphorus catalysts derived from (S)-binaphthol for highly enantioselective reduction of acetophenone by borane
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New chiral (+)-2,2'-O,O-(1,1'-binaphthyl)-dioxo-N,N-diethylphospholidine 1 and its borane complex 3 were prepared from (S)-binaphthol and their use as catalysts in enantioselective borane reductions of prochiral acetophenone were investigated. Enantiomeri
- Ma, Margaret F. P.,Li, Kangying,Zhou, Zhenghong,Tang, Chuchi,Chan, Albert S. C.
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- Relationship between structure, fluxionality and racemization activity in organometallic derivatives of polyoxometalates
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The catalytic activity of several organometallic derivatives of polyoxometalates, especially those of general formula [M4O16{M′(η6-arene)}4] (M = Mo, W; M′ = Ru, Os), was evaluated in the racemization of secondary alcohols. A link between composition, fluxionality and catalytic activity was established.
- Laurencin, Danielle,Villanneau, Richard,Proust, Anna,Brethon, Anne,Arends, Isabel W.C.E.,Sheldon, Roger A.
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- Designer Outer Membrane Protein Facilitates Uptake of Decoy Molecules into a Cytochrome P450BM3-Based Whole-Cell Biocatalyst
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We report an OmpF loop deletion mutant, which improves the cellular uptake of external additives into an Escherichia coli whole-cell biocatalyst. Through co-expression of the OmpF mutant with wild-type P450BM3 in the presence of decoy molecules, the yield
- Karasawa, Masayuki,Shoji, Osami,Stanfield, Joshua Kyle,Suzuki, Kazuto,Yonemura, Kai
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supporting information
(2021/12/16)
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- 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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- Epoxide Hydrogenolysis Catalyzed by Ruthenium PNN and PNP Pincer Complexes
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The metal-catalyzed hydrogenolysis of epoxides to give alcohols has advanced rapidly in the past several years, with some catalysts selectively giving linear (anti-Markovnikov) products and other catalysts providing branched (Markovnikov) products. The currently known branched-selective catalyst systems require catalyst loadings of 1% or higher and typically require a strong base additive. We report herein that PNN- and PNP-ruthenium pincer complexes containing N-H functional groups are highly active for branched-selective hydrogenolysis of epoxides. When isopropyl alcohol is used as the solvent, excellent yields of the branched alcohol products are obtained without strongly basic additives, using catalyst loadings as low as 0.03%. Epoxides with a directly attached secondary carbon give a very high (>99:1) selectivity for the branched products. Aryl-substituted epoxides give branched:linear ratios ranging from 2.7 to 19.0. For aryl epoxides, a PNP-Ru catalyst showed a greater preference for the branched product than a PNN-Ru catalyst, and substrates with electron-rich aryl substituents showed a lower preference for the branched product.
- Borden, Olivia J.,Chianese, Anthony R.,Head, Marianna C.,Kelly, Sophie E.,Kirlin, Fallyn L.
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supporting information
p. 1025 - 1033
(2022/04/25)
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- Chromoselective Photocatalysis Enables Stereocomplementary Biocatalytic Pathways**
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Controlling the selectivity of a chemical reaction with external stimuli is common in thermal processes, but rare in visible-light photocatalysis. Here we show that the redox potential of a carbon nitride photocatalyst (CN-OA-m) can be tuned by changing the irradiation wavelength to generate electron holes with different oxidation potentials. This tuning was the key to realizing photo-chemo-enzymatic cascades that give either the (S)- or the (R)-enantiomer of phenylethanol. In combination with an unspecific peroxygenase from Agrocybe aegerita, green light irradiation of CN-OA-m led to the enantioselective hydroxylation of ethylbenzene to (R)-1-phenylethanol (99 % ee). In contrast, blue light irradiation triggered the photocatalytic oxidation of ethylbenzene to acetophenone, which in turn was enantioselectively reduced with an alcohol dehydrogenase from Rhodococcus ruber to form (S)-1-phenylethanol (93 % ee).
- Schmermund, Luca,Reischauer, Susanne,Bierbaumer, Sarah,Winkler, Christoph K.,Diaz-Rodriguez, Alba,Edwards, Lee J.,Kara, Selin,Mielke, Tamara,Cartwright, Jared,Grogan, Gideon,Pieber, Bartholom?us,Kroutil, Wolfgang
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supporting information
p. 6965 - 6969
(2021/03/03)
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- PNO ligand containing planar chiral ferrocene and application thereof
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The invention discloses a PNO ligand containing planar chiral ferrocene and application thereof. The PNO ligand containing planar chiral ferrocene is a planar chiral ferrocene-containing and phenol-containing PNO ligand as shown in a general formula (I) or (II) which is described in the specification, or a planar chiral ferrocene-containing and aryl-phosphoric-acid-containingPNO ligand containing as shown in a general formula (III) or (IV) which is described in the specification, or a planar chiral ferrocene-containing and carbon-chiral-phenol-containingPNO ligand as shown in a general formula (V) or (VI) which is described in the specification. The invention provides tridentate PNO ligands and processes for their complexation with transition metal salts or transition metal complexes; the introduction of salicylaldehyde and derivatives thereof, which are simple and easy to obtain, enables the ligands to have a bifunctionalization effect, and -OH in a formed catalyst has stronger acidity and is beneficial to combination with N/O in polar double bonds. Therefore, due to the bifunctionalization effect of the catalyst, the interaction between the catalyst and a substrate can be greatly improved, so a reaction can obtain higher catalytic activity and stereoselectivity.
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Paragraph 0099-0110; 0122-0124
(2021/06/21)
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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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- 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.
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Paragraph 0038-0043; 0118-0141; 0145-015
(2021/05/29)
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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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- Enantioselective oxidation of secondary alcohols by the flavoprotein alcohol oxidase from Phanerochaete chrysosporium
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The enantioselective oxidation of secondary alcohols represents a valuable approach for the synthesis of optically pure compounds. Flavoprotein oxidases can catalyse such selective transformations by merely using oxygen as electron acceptor. While many flavoprotein oxidases preferably act on primary alcohols, the FAD-containing alcohol oxidase from Phanerochaete chrysosporium was found to be able to perform kinetic resolutions of several secondary alcohols. By selective oxidation of the (S)-alcohols, the (R)-alcohols were obtained in high enantiopurity. In silico docking studies were carried out in order to substantiate the observed (S)-selectivity. Several hydrophobic and aromatic residues in the substrate binding site create a cavity in which the substrates can comfortably undergo van der Waals and pi-stacking interactions. Consequently, oxidation of the secondary alcohols is restricted to one of the two enantiomers. This study has uncovered the ability of an FAD-containing alcohol oxidase, that is known for oxidizing small primary alcohols, to perform enantioselective oxidations of various secondary alcohols.
- Tjallinks, Gwen,Martin, Caterina,Fraaije, Marco W.
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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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- Chitosan as a chiral ligand and organocatalyst: Preparation conditions-property-catalytic performance relationships
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Chitosan is an abundant and renewable chirality source of natural origin. The effect of the preparation conditions by alkaline hydrolysis of chitin on the properties of chitosan was studied. The materials obtained were used as ligands in the ruthenium-catalysed asymmetric transfer hydrogenation of aromatic prochiral ketones and oxidative kinetic resolution of benzylic alcohols as well as organocatalysts in the Michael addition of isobutyraldehyde to N-substituted maleimides. The degrees of deacetylation of the prepared materials were determined by 1H NMR, FT-IR and UV-vis spectroscopy, the molecular weights by viscosity measurements, their crystallinity by WAXRD, and their morphology by SEM and TEM investigations. The materials were also characterized by Raman spectroscopy. The biopolymers which have molecular weights in a narrow (200-230 kDa) range and appropriate (80-95%) degrees of deacetylation were the most efficient ligands in the enantioselective transfer hydrogenation, whereas in the oxidative kinetic resolution the activity of the complexes and the stereoselectivity increased with the degree of deacetylation. The chirality of the chitosan was sufficient to obtain enantioselection in the Michael addition of isobutyraldehyde to maleimides in the aqueous phase. Interestingly, the biopolymer afforded the opposite enantiomer in excess compared to the monomer, d-glucosamine. In this reaction, good correlation between the degree of deacetylation and the catalytic activity was found. These results are novel steps in the application of this natural, biocompatible and biodegradable polymer in developing environmentally benign methods for the production of optically pure fine chemicals.
- Kolcsár, Vanessza Judit,Sz?ll?si, Gy?rgy
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p. 7652 - 7666
(2021/12/13)
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- Enantioselective resolution of (±)-1-phenylethyl acetate using the immobilized extracellular proteases from deep-sea Bacillus sp. DL-1
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Bacillus sp. DL-1 was isolated from the deep sea of the Western Pacific Ocean and behaved very good resistance to NaCl. The extracellular proteases of Bacillus sp. DL-1 were found to exhibit excellent enantioselectivity for the kinetic resolution of (±)-1-phenylethyl acetate. To improve the stability of the enzyme, the immobilized extracellular proteases were preparated by using 60 g kieselguhr and 1-L crude fermentation broth containing extracellular proteases of Bacillus sp. DL-1, shaking at 25 °C, 200 r/min for 10 h. Every gram of kieselguhr adsorbed 25.7 mg extracellular protease and the enzymatic activity recovery was 79.86%. The immobilized proteases preserved about 35.8% of its activity after 6 repeated uses, which were also used as biocatalyst to asymmetrically hydrolyse (±)-1-phenylethyl acetate for the preparation of (R)-1-phenylethanol and (S)-1-phenylethyl acetate with high optical purities. The effects of pH, temperature, enzyme concentration, substrate concentration, reaction time and additives (metal ions/surfactants) on the resolution were investigated by single factor experiments. Under the optimal reaction conditions (10 mM (±)-1-phenylethyl acetate, 40 mg/mL immobilized extracellular proteases, pH 7.5 (Tris-HCl), 5% (v/v) methanol and 45 °C for 2 h), (R)-1-phenylethanol was generated with the e.e.p being > 97%, and the yield being 53%, respectively. Analogously, under the optimal reaction conditions (10-mM (±)-1-phenylethyl acetate, 360 mg/mL immobilized extracellular proteases, pH 6.0 (PB), 5% (v/v) DMSO and 35 °C for 1.5 h), (S)-1-phenylethyl acetate was generated with the e.e.s being over 99% and the yield being 79%, respectively. Compared with the extracellular proteases from Bacillus sp. DL-2, the immobilized extracellular proteases from Bacillus sp. DL-1 exhibited higher hydrolytic activity and could asymmetrically hydrolyse (±)-1-phenylethyl acetate by using higher substrate concentrations, shorter reaction times to obtain higher yields. Notably, the extracellular proteases of Bacillus sp. DL-1 were demonstrated to behave the same enantio-preference as those of most other reported esterases/lipases. Proteases from deep-sea Bacillus sp. DL-1 are promising biocatalysts for the synthesis of valuable chiral chemicals.
- Dong, Lu,Qi, Shujuan,Jia, Jianwei,Zhang, Yun,Hu, Yunfeng
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- Two Approaches for CAL-B-Catalyzed Enantioselective Deacylation of a Set of α-Phenyl Ethyl Esters: Organic Solvent with Sodium Carbonate and Micro-aqueous Medium
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Herein, we report an efficient enantioselective cleavage of the acyl- moiety of a set of α- phenyl ethyl esters with different chain-lengths catalyzed by lipase B from Candida antarctica (CAL-B) by comparing two reactional approaches: anhydrous media with sodium carbonates and micro-aqueous medium. The deacylation is performed in organic solvent, in the presence of Na2CO3 in the first case, and by addition of a drop of phosphate buffer solution pH 7 in the second. The results show the high efficiency of the deacylation in the presence of the sodium carbonate for the enzymatic resolution of all the esters and that in term of reactivity (31% ≤ conv ≤ 50%) and selectivity (E > 200). While, during the hydrolysis in micro-aqueous media, the conversion is strongly affected by the length of the acyl-chain side, the conversion decreases from conv = 50% with the 1-phenylethyl acetate 1a to conv = 19% with 1-phenyethyl dodecanoate 6a, and this, even if the selectivity remains high (E > 89). In both conditions, the lipase CAL-B shows a high enantioselectivities in favor of (R)-1-phenyl ethanol enantiomer (conv > 45%, E > 200) but the reactivity is modulated by the form and the size of the acyl-chain side. Graphic Abstract: [Figure not available: see fulltext.].
- Razi, Samra,Zeror, Saoussen,Merabet-Khelassi, Mounia,Kolodziej, Emilie,Toffano, Martial,Aribi-Zouioueche, Louisa
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p. 2603 - 2611
(2021/01/15)
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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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- To Rebound or...Rebound? Evidence for the "alternative Rebound" mechanism in Ca'H Oxidations by the systems nonheme Mn Complex/H2O2/carboxylic acid
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In this work, it has been shown that aliphatic Ca'H oxidations by bioinspired catalyst systems Mn aminopyridine complex/H2O2/carboxylic acid in acetonitrile afford predominantly a mixture of the corresponding alcohol and the ester. The alcohol/ester ratio is higher for catalysts bearing electron-donating groups at the aminopyridine core. Isotopic labeling studies witness that the oxygen atom of the alcohol originates from the H2O2molecule, while the ester oxygen comes exclusively from the acid. Oxidation of ethylbenzene in the presence of acetic acid affords enantiomerically enriched 1-phenylethanol and 1-phenyl acetate, with close enantioselectivities and the same sign of absolute chirality. Experimental data and density functional theory calculations provide evidence in favor of the rate-limiting benzylic H atom abstraction by the high-spin (S = 1) [LMnV(O)OAc]2+active species followed by competitive OH/OC(O)R rebound. This mechanism has been unprecedented for Ca'H oxidations catalyzed by bioinspired Mn complexes. The trends governing the alcohol/ester ratios have been rationalized in terms of steric properties of the catalyst, acid, and substrate. copy; 2021 American Chemical Society.
- Ottenbacher, Roman V.,Bryliakova, Anna A.,Shashkov, Mikhail V.,Talsi, Evgenii P.,Bryliakov, Konstantin P.
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p. 5517 - 5524
(2021/05/31)
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- Exploration of highly electron-rich manganese complexes in enantioselective oxidation catalysis; A focus on enantioselective benzylic oxidation
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The direct enantioselective hydroxylation of benzylic C-H bonds to form chiral benzylic alcohols represents a challenging transformation. Herein, we report on the exploration of new biologically inspired manganese and iron complexes bearing highly electron-rich aminopyridine ligands containing 4-pyrrolidinopyridine moieties ((S,S)-1, (R,R)-1, 2 and 5) in combination with chiral bis-pyrrolidine and N,N-cyclohexanediamine backbones in enantioselective oxidation catalysis with aqueous H2O2. The current manganese complexes outperform the analogous manganese complexes containing 4-dimethylaminopyridine moieties (3 and 4) in benzylic oxidation reactions in terms of alcohol yield while keeping similar ee values (~60% ee), which is attributed to the higher basicity of the 4-pyrrolidinopyridine group. A detailed investigation of different carboxylic acid additives in enantioselective benzylic oxidation provides new insights into how to rationally enhance enantioselectivities by means of proper tuning of the environment around the catalytic active site, and has resulted in the selection of Boc-l-Tert-leucine as the preferred additive. Using these optimized conditions, manganese complex 2 was shown to be effective in the enantioselective benzylic oxidation of a series of arylalkane substrates with up to 50% alcohol yield and 62% product ee. A final set of experiments also highlights the use of the new 4-pyrrolidinopyridine-based complexes in the asymmetric epoxidation of olefins (up to 98% epoxide yield and >99% ee).
- Klein Gebbink, Robertus J. M.,Li, Fanshi,Lutz, Martin,Masferrer-Rius, Eduard
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p. 7751 - 7763
(2021/12/13)
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- Structural and Biochemical Studies Enlighten the Unspecific Peroxygenase from Hypoxylon sp. EC38 as an Efficient Oxidative Biocatalyst
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Unspecific peroxygenases (UPOs) are glycosylated fungal enzymes that can selectively oxidize C-H bonds. UPOs employ hydrogen peroxide as the oxygen donor and reductant. With such an easy-to-handle cosubstrate and without the need for a reducing agent, UPOs are emerging as convenient oxidative biocatalysts. Here, an unspecific peroxygenase from Hypoxylon sp. EC38 (HspUPO) was identified in an activity-based screen of six putative peroxygenase enzymes that were heterologously expressed in Pichia pastoris. The enzyme was found to tolerate selected organic solvents such as acetonitrile and acetone. HspUPO is a versatile catalyst performing various reactions, such as the oxidation of prim- and sec-alcohols, epoxidations, and hydroxylations. Semipreparative biotransformations were demonstrated for the nonenantioselective oxidation of racemic 1-phenylethanol rac-1b (TON = 13 000), giving the product with 88% isolated yield, and the oxidation of indole 6a to give indigo 6b (TON = 2800) with 98% isolated yield. HspUPO features a compact and rigid three-dimensional conformation that wraps around the heme and defines a funnel-shaped tunnel that leads to the heme iron from the protein surface. The tunnel extends along a distance of about 12 ? with a fairly constant diameter in its innermost segment. Its surface comprises both hydrophobic and hydrophilic groups for dealing with substrates of variable polarities. The structural investigation of several protein-ligand complexes revealed that the active site of HspUPO is accessible to molecules of varying bulkiness with minimal or no conformational changes, explaining the relatively broad substrate scope of the enzyme. With its convenient expression system, robust operational properties, relatively small size, well-defined structural features, and diverse reaction scope, HspUPO is an exploitable candidate for peroxygenase-based biocatalysis.
- Ebner, Katharina,Glieder, Anton,Kroutil, Wolfgang,Mattevi, Andrea,Rinnofner, Claudia,Rotilio, Laura,Swoboda, Alexander
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p. 11511 - 11525
(2021/09/22)
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- Comparison of nonheme manganese‐ and iron‐containing flavone synthase mimics
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Heme and nonheme‐type flavone synthase enzymes, FS I and FS II are responsible for the synthesis of flavones, which play an important role in various biological processes, and have a wide range of biomedicinal properties including antitumor, antimalarial, and antioxidant activities. To get more insight into the mechanism of this curious enzyme reaction, nonheme structural and functional models were carried out by the use of mononuclear iron, [FeII(CDA‐BPA*)]2+ (6) [CDA‐BPA = N,N,N’,N’‐tetrakis‐(2‐pyridylmethyl)‐cyclohexanediamine], [FeII(CDA‐BQA*)]2+ (5) [CDA‐BQA = N,N,N’,N’‐tetrakis‐(2‐quinolilmethyl)‐cyclohexanediamine], [FeII(Bn‐TPEN)(CH3CN)]2+ (3) [Bn‐ TPEN = N‐benzyl‐N,N’,N’‐tris(2‐pyridylmethyl)‐1,2‐ diaminoethane], [FeIV(O)(Bn‐TPEN)]2+ (9), and manganese, [MnII(N4Py*)(CH3CN)]2+ (2) [N4Py* = N,N‐bis(2‐pyridylmethyl)‐1,2‐di(2‐pyridyl)ethyl-amine)], [MnII(Bn‐TPEN)(CH3CN)]2+ (4) complexes as catalysts, where the possible reactive inter-mediates, high‐valent FeIV(O) and MnIV(O) are known and well characterised. The results of the catalytic and stoichiometric reactions showed that the ligand framework and the nature of the metal cofactor significantly influenced the reactivity of the catalyst and its intermediate. Comparing the reactions of [FeIV(O)(Bn‐TPEN)]2+ (9) and [MnIV(O)(Bn‐TPEN)]2+ (10) towards flavanone under the same conditions, a 3.5‐fold difference in reaction rate was observed in favor of iron, and this value is three orders of magnitude higher than was observed for the previously published [FeIV(O)(N2Py2Q*)]2+ [N,N‐bis(2‐quinolylmethyl)‐1,2‐di(2‐pyridyl)ethylamine] species.
- Juraj, Natalija Pantalon,Kaizer, József,Kirin, Sre?ko I.,Lakk‐bogáth, Dóra,Meena, Bashdar I.,Peri?, Berislav
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- Homogeneous Palladium-Catalyzed Selective Reduction of 2,2′-Biphenols Using HCO 2H as Hydrogen Source
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An efficient homogeneous palladium-catalyzed selective deoxygenation of 2,2′-biphenols by reduction of aryl triflates with HCO 2H as the hydrogen source is reported. This protocol complements the current method based on heterogeneous Pd/C-catalyzed hydrogenation with hydrogen gas. This process provided the reduction products in good to excellent yields, which could be readily converted to various synthetically useful molecules, especially ligands for catalytic synthesis.
- Li, Ruoling,Li, Chenchen,Yang, Wen,Zhao, Wanxiang
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p. 1605 - 1618
(2021/02/01)
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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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- 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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- 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.
- Stanley, Levi M.,Tran, Hai N.
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supporting information
(2021/12/27)
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- Synthesis, characterization and catalytic performance in enantioselective reactions by mesoporous silica materials functionalized with chiral thiourea-amine ligand
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Chiral heterogeneous catalysts have been synthesized by grafting of silyl derivatives of (1R, 2R)- or (1S, 2S)-1,2-diphenylethane-1,2-diamine on SBA-15 mesoporous support. The mesoporous material SBA-15 and so-prepared chiral heterogeneous catalysts were characterized by a combination of different techniques such as X-ray diffractometry (XRD), Fourier transform infrared (FT-IR), thermogravimetric analysis (TGA), field emission scanning electron microscopy (FESEM), and Brunauer–Emmett–Teller (BET) surface area. Results showed that (1R, 2R)- and (1S, 2S)-1,2-diphenylethane-1,2-diamine were successively immobilized on SBA-15 mesoporous support. Chiral heterogeneous catalysts and their homogenous counterparts were tested in enantioselective transfer hydrogenation of aromatic ketones and enantioselective Michael addition of acetylacetone to β-nitroolefin derivatives. The catalysts demonstrated notably high catalytic conversions (up to 99%) with moderate enantiomeric excess (up to 30% ee) for the heterogeneous enantioselective transfer hydrogenation. The catalytic performances for enantioselective Michael reaction showed excellent activities (up to 99%) with poor enantioselectivities. Particularly, the chiral heterogeneous catalysts could be readily recycled for Michael reaction and reused in three consecutive catalytic experiments with no loss of catalytic efficacies.
- G?k, Ya?ar,G?k, Halil Zeki
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p. 853 - 874
(2020/11/10)
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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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- PQXdpap: Helical Poly(quinoxaline-2,3-diyl)s Bearing 4-(Dipropylamino)pyridin-3-yl Pendants as Chirality-Switchable Nucleophilic Catalysts for the Kinetic Resolution of Secondary Alcohols
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Helically chiral poly(quinoxaline-2,3-diyl)s bearing 4-(dipropylamino)pyridin-3-yl pendants at the 5-position of the quinoxaline ring (PQXdpap) exhibited high catalytic activities and moderate to high selectivities (up to s = 87) in the acylative kinetic resolution of secondary alcohols. The solvent-dependent helical chirality switching of PQXdpap between pure toluene and a 1:1 mixture of toluene and 1,1,2-trichloroethane enabled the preparation of either compound of a pair of enantiomerically pure alcohols (>99% ee) from a single catalyst.
- Murakami, Ryo,Suginome, Michinori,Yamamoto, Takeshi
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supporting information
p. 8711 - 8716
(2021/11/24)
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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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- 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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- A NEW TEMPLATE of MITSUNOBU ACYLATE CLEAVABLE in NONALKALINE CONDITIONS
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The Mitsunobu inversion is one of the reliable methods for stereospecific substitution of chiral alcohols, but its deacylation step has limited the substrate scope. Here, we propose a new template of the Mitsunobu acylate that can be deacylated in non-alkaline treatments. The 3,4-dihydroxy-2-methylenebutanoate was selected as a template structure, and its acetonide- or bisTBS derivatives were synthesized. The latter especially showed excellent inversion efficiency (up to >99% ee) and good elimination performance for a series of secondary alcohols in near-neutral conditions. The results demonstrated the applicability of the new template for the substrates labile in alkaline conditions, such as a-hydroxyesters.
- Sai, Yusuke,Sakakibara, Yoshimichi,Shigetomi, Kengo,Ubukata, Makoto,Uraki, Yasumitsu
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p. 140 - 158
(2022/01/08)
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- Aliphatic C–H hydroxylation activity and durability of a nickel complex catalyst according to the molecular structure of the bis(oxazoline) ligands
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Applicability of the oxazoline-based compounds, bis(2-oxazolynyl)methane (BOX) and 2,6-bis(2-oxazolynyl)pyridine (PyBOX), as supporting ligands of nickel(II) complexes for the catalysis of aliphatic C–H hydroxylation with m-CPBA (meta-chloroperoxybenzoic acid) was explored. Substituent groups at the fourth and fifth positions of oxazoline rings and the bridgehead carbon atom of the BOX derivatives affected the catalytic performances toward cyclohexane hydroxylation. Presence of dioxygen led to a reduced catalytic performance of the nickel complexes, except in the case of a fully substituted BOX ligand complex.
- Hikichi, Shiro,Izumi, Takashi,Matsuba, Naki,Nakazawa, Jun
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- Asymmetric Hydrosilylation of β-Silyl Styrenes Catalyzed by a Chiral Palladium Complex
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A palladium complex coordinated with a chiral SIPHOS ligand was evaluated as an efficient catalyst for asymmetric hydrosilylation of β-silyl styrenes with trichlorosilane and 23 1,2-bis(silyl) chiral compounds were produced. Good to excellent enantioselec
- He, Yu-Han,Ji, Yang,Li, Rui,Su, Yan,Wang, Yi-Fan
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- An Enantioconvergent Benzylic Hydroxylation Using a Chiral Aryl Iodide in a Dual Activation Mode
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The application of a triazole-substituted chiral iodoarene in a direct enantioselective hydroxylation of alkyl arenes is reported. This method allows the rapid synthesis of chiral benzyl alcohols in high yields and stereocontrol, despite its nontemplated nature. In a cascade activation consisting of an initial irradiation-induced radical C-H-bromination and a consecutive enantioconvergent hydroxylation, the iodoarene catalyst has a dual role. It initiates the radical bromination in its oxidized state through an in-situ-formed bromoiodane and in the second, Cu-catalyzed step, it acts as a chiral ligand. This work demonstrates the ability of a chiral aryl iodide catalyst acting both as an oxidant and as a chiral ligand in a highly enantioselective C-H-activating transformation. Furthermore, this concept presents an enantioconvergent hydroxylation with high selectivity using a synthetic catalyst.
- Abazid, Ayham H.,Clamor, Nils,Nachtsheim, Boris J.
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p. 8042 - 8048
(2020/09/21)
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- Natural Deep Eutectic Solvents as Performance Additives for Peroxygenase Catalysis
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Natural deep eutectic solvents (NADES) are proposed as alternative solvents for peroxygenase-catalysed oxyfunctionalization reactions. Choline chloride-based NADES are of particular interest as they can serve as solvent, enzyme-stabiliser and sacrificial electron donor for the in situ H2O2 generation. This report provides the first proof-of-concept and basic characterisation of this new reaction system. Highly promising turnover numbers for the biocatalysts of up to 200,000 have been achieved.
- Ma, Yunjian,Li, Yongru,Ali, Shahid,Li, Peilin,Zhang, Wuyuan,Rauch, Marine C. R.,Willot, Sébastien J.-P.,Ribitsch, Doris,Choi, Young Hae,Alcalde, Miguel,Hollmann, Frank,Wang, Yonghua
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p. 989 - 994
(2019/12/27)
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- Enantiocomplementary C–H Bond Hydroxylation Combining Photo-Catalysis and Whole-Cell Biocatalysis in a One-Pot Cascade Process
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Enantiocomplementary hydroxylation of alkyl aromatics through a one-pot photo-biocatalytic cascade reaction is described. The photoredox process is implemented in aqueous phase with O2 as oxidant and the subsequent (R)- or (S)-selective bioreduction is performed by whole cell system without the addition of the expensive cofactor (NADPH). This mild, operationally simple protocol transforms a wide variety of readily available aromatic compounds into valuable chiral alcohols with high yield (up to 90 %) and stereoselectivity (up to 99 %), thereby displaying important potentials in organic synthesis.
- Peng, Yongzhen,Li, Danyang,Fan, Jiajie,Xu, Weihua,Xu, Jian,Yu, Huilei,Lin, Xianfu,Wu, Qi
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p. 821 - 825
(2020/02/20)
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- FOx News: Towards Methanol-driven Biocatalytic Oxyfunctionalisation Reactions
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The novel formate oxidase from Aspergillus oryzae (AoFOx) is a useful catalyst to promote H2O2-dependent oxyfunctionalisation reactions. In this contribution we exploit the substrate promiscuity of AoFOx to fully oxidise methanol and formaldehyde to CO2 and drive peroxygenase-catalysed stereoselective oxyfunctionalisation reactions. The highly atom efficient H2O2 generation system also enabled high catalytic turnover of the peroxygenase production enzyme.
- Willot, Sébastien J.-P.,Hoang, Manh Dat,Paul, Caroline E.,Alcalde, Miguel,Arends, Isabel W. C. E.,Bommarius, Andreas S.,Bommarius, Bettina,Hollmann, Frank
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p. 2713 - 2716
(2020/04/03)
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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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- 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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- Green synthesis of chiral aromatic alcohols with Lactobacillus kefiri P2 as a novel biocatalyst
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Biocatalytic reduction is a very important field of research in synthetic organic chemistry. Herein, three different Lactic Acid Bacteria (LAB) strains were evaluated for their bioreduction potential using acetophenone as a model substrate. Among these strains, Lactobacillus kefiri P2 strain was determined as the best asymmetric reduction biocatalyst. Reaction optimization parameters such as reaction time, temperature, agitation speed and pH were systematically optimized using Lactobacillus kefiri P2 strain and model substrate acetophenone. Under these optimized reaction conditions, secondary chiral alcohols were obtained by bioreduction of various prochiral ketones with results up to 99% enantiomeric excess. In addition, the steric and electronic effects of substituents on enantioselectivity and conversion were evaluated. It has been shown that Lactobacillus kefiri P2 biocatalyst was an effective catalyst for asymmetric reduction. This method provides an environmentally friendly method for the synthesis of optically pure alcohols and an alternative approach to chemical catalysts.
- Bayda?, Yasemin,Dertli, Enes,?ahin, Engin
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p. 1035 - 1045
(2020/03/03)
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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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- 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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- 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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- Enantioselective Hydroxylation of Benzylic C(sp3)-H Bonds by an Artificial Iron Hydroxylase Based on the Biotin-Streptavidin Technology
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The selective hydroxylation of C-H bonds is of great interest to the synthetic community. Both homogeneous catalysts and enzymes offer complementary means to tackle this challenge. Herein, we show that biotinylated Fe(TAML)-complexes (TAML = Tetra Amido Macrocyclic Ligand) can be used as cofactors for incorporation into streptavidin to assemble artificial hydroxylases. Chemo-genetic optimization of both cofactor and streptavidin allowed optimizing the performance of the hydroxylase. Using H2O2 as oxidant, up to ~300 turnovers for the oxidation of benzylic C-H bonds were obtained. Upgrading the ee was achieved by kinetic resolution of the resulting benzylic alcohol to afford up to >98% ee for (R)-tetralol. X-ray analysis of artificial hydroxylases highlights critical details of the second coordination sphere around the Fe(TAML) cofactor.
- Barnet, Maxime,Peterson, Ryan L.,Rebelein, Johannes G.,Rumo, Corentin,Serrano-Plana, Joan,Ward, Thomas R.
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supporting information
p. 10617 - 10623
(2020/07/04)
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- Highly enantioselective undirected catalytic hydroxylation of benzylic CH2 groups with H2O2
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Chiral bis-amine-bis-pyridine Mn complexes of the type [LMnII(OTf)2] (L is 2,2?-bipyrrolidine derived chiral ligand, bearing trifluoroethoxy and methyl substituents), efficiently catalyze the enantioselective hydroxylation of organic substrates at benzylic CH2 positions with H2O2. The use of β-polyfluorinated alcohols instead of CH3CN as the reaction solvents enhances the yield of chiral secondary alcohol from 5–6percent up to 50–70percent. The enantiomeric purity of the alcohol can be further increased (up to 97percent ee) by diluting the mixture with CH3CN at late stage, which facilitates stereoconvergent oxidative kinetic resolution of the alcohol formed. Using this one-pot sequential asymmetric hydroxylation/oxidative kinetic resolution approach, the oxidation of a series of 3,4-dihydrocoumarin derivatives and 3,4-dihydroquinolinone has been realized, affording the target 4-hydroxo compounds in 40–60percent isolated yield and in up to 93percent ee. Besides the 4-hydroxo derivatives, formation of 3,4-epoxidation and 3,4-desaturation byproducts has been observed in some cases, thus providing evidence for unprecedented substrate-dependent hydroxylase/desaturase/epoxidase reactivity of bis-amine-bis-pyridine Mn complexes.
- Bryliakov, Konstantin P.,Ottenbacher, Roman V.,Talsi, Evgenii P.
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p. 170 - 177
(2020/08/28)
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- Characterization of a Self-Sufficient Cytochrome P450 Monooxygenase from Deinococcus apachensis for Enantioselective Benzylic Hydroxylation
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A self-sufficient cytochrome P450 monooxygenase from Deinococcus apachensis (P450DA) was identified and successfully overexpressed in Escherichia coli BL21(DE3). P450DA would be a member of the CYP102D subfamily and assigned as CYP102D2 according to the phylogenetic tree and sequence alignment. Purification and characterization of the recombinant P450DA indicated both NADH and NADPH could be used by P450DA as a reducing cofactor. The recombinant E. coli (P450DA) strain was functionally active, showing excellent enantioselectivity for benzylic hydroxylation of methyl 2-phenylacetate. Further substrate scope studies revealed that P450DA is able to catalyze benzylic hydroxylation of a variety of compounds, affording the corresponding chiral benzylic alcohols in 86–99 % ee and 130–1020 total turnover numbers.
- Xie, Lingzhi,Chen, Ke,Cui, Haibo,Wan, Nanwei,Cui, Baodong,Han, Wenyong,Chen, Yongzheng
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p. 1820 - 1825
(2020/03/05)
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- Enantioselective Bioamination of Aromatic Alkanes Using Ammonia: A Multienzymatic Cascade Approach
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Chiral amines are common drug building blocks and important active pharmaceutical ingredients. Preparing these functionalized compounds from simple materials, such as alkanes, is of great interest. We recently developed an artificial bioamination cascade for the C?H amination of cyclic alkanes by combining P450 monooxygenase, alcohol dehydrogenase, and amine dehydrogenase. Herein, this system has been extended to the synthesis of chiral aromatic amines. In the first hydroxylation step, process optimization increased the conversion to 77 %. Two stereoselectively complementary alcohol dehydrogenases and an amine dehydrogenase were selected for the bioconversion of aromatic hydrocarbons to amines. The amination reaction was optimized with respect to cofactor addition and enzyme dosage. Isopropanol was added to decrease ketone intermediate accumulation in the amination step, which further enhanced the overall conversion. This cascade system converted a panel of hydrocarbon substrates into the corresponding amines with excellent optical purity (>99 % ee) and moderate conversion ratios (13–53 %).
- Chen, Fei-Fei,Wang, Hui,Xu, Jian-He,Yu, Hui-Lei,Zheng, Yu-Cong
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- Asymmetric transfer hydrogenation of arylketones catalyzed by enantiopure ruthenium(II)/pybox complexes containing achiral phosphonite and phosphinite ligands
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A family of complexes of the formula trans-[RuCl2(L)(R-pybox)] (R-pybox = (S,S)-iPr-pybox, (R,R)-Ph-pybox, L = monodentate phosphonite, PPh(OR)2, and phosphinite, L = PPh2(OR), ligands) were screened in the catalytic asymmetric transfer hydrogenation of acetophenone, observing a strong influence of the nature of both the R-pybox substituents and the L ligand in the process. The best results were obtained with complex trans-[RuCl2{PPh2(OEt)}{(R,R)-Ph-pybox}] (2c), which provided high conversion and enantioselectivity (up to 96% enantiomeric excess, e.e.) for the reduction of a variety of aromatic ketones, affording the (S)-benzylalcohols.
- Claros, Miguel,Díez, Josefina,De Julián, Eire,Gamasa, M. Pilar,Lastra, Elena
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