- Stereoselective Two-Step Biocatalysis in Organic Solvent: Toward All Stereoisomers of a 1,2-Diol at High Product Concentrations
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Biotransformations on larger scale are mostly limited to cases in which alternative chemical routes lack sufficient chemo-, regio-, or stereoselectivity. Here, we expand the applicability of biocatalysis by combining cheap whole cell catalysts with a microaqueous solvent system. Compared to aqueous systems, this permits manifoldly higher concentrations of hydrophobic substrates while maintaining stereoselectivity. We apply these methods to four different two-step reactions of carboligation and oxidoreduction to obtain 1-phenylpropane-1,2-diol (PPD), a versatile building block for pharmaceuticals, starting from inexpensive aldehyde substrates. By a modular combination of two carboligases and two alcohol dehydrogenases, all four stereoisomers of PPD can be produced in a flexible way. After thorough optimization of each two-step reaction, the resulting processes enabled up to 63 g L-1 product concentration (98% yield), space-time-yields up to 144 g L-1 d-1, and a target isomer content of at least 95%. Despite the use of whole cell catalysts, we did not observe any side product formation of note. In addition, we prove that, by using 1,5-pentandiol as a smart cosubstrate, a very advantageous cofactor regeneration system could be applied.
- Wachtmeister, Jochen,Jakoblinnert, Andre,Rother, D?rte
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- An Enzymatic 2-Step Cofactor and Co-Product Recycling Cascade towards a Chiral 1,2-Diol. Part II: Catalytically Active Inclusion Bodies
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Optimal performance of multi-step enzymatic one-pot cascades requires a facile balance between enzymatic activity and stability of multiple enzymes under the employed reaction conditions. We here describe the optimization of an exemplary two-step one-pot
- J?ger, Vera D.,Piqueray, Maja,Seide, Selina,Pohl, Martina,Wiechert, Wolfgang,Jaeger, Karl-Erich,Krauss, Ulrich
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- A two-step biocatalytic cascade in micro-aqueous medium: Using whole cells to obtain high concentrations of a vicinal diol
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Although single- and multi-step biocatalytic approaches show persuasive advantages for the synthesis of especially chiral compounds (e.g. high chemo- and stereoselectivity), their application often suffers from low substrate loads and hence low space-time-yields. We herein present a synthetic cascade approach in which lyophilised, recombinant whole cells are applied in micro-aqueous reaction systems yielding extremely high space-time-yields. As an example we investigated the two-step synthesis of 1-phenylpropane-1,2-diol starting from cheap aldehydes and achieved high selectivities (ee/de > 99%) and high product concentrations. The new concept of running biocatalytic cascades in a mixture of high substrate loads and organic solvents under addition of small amounts of highly concentrated buffer is not only very easy-to-apply, but also exhibits several economic and ecologic advantages. On the one hand the usage of whole, lyophilised cells circumvents time-consuming enzyme purification as well as addition of expensive cofactors (here ThDP and NADPH). Additionally, catalyst and product workup is facilitated by the application of organic solvents (here MTBE). On the other hand, the employment of whole cells very effectively circumvents stability problems of biocatalysts in unconventional media enabling the addition of extremely high substrate loads (up to 500 mM in our example) and is therefore an easy and effective approach for multi-step biocatalysis. After optimisation, the combination of a carboligation step followed by a second oxidoreduction step with whole cell catalysts afforded an efficient two-step cascade for the production of 1-phenylpropane-1,2-diol with space-time yields up to 327 g L-1 d-1 and an E-factor of 21.3 kg waste kgproduct-1. This journal is the Partner Organisations 2014.
- Jakoblinnert, Andre,Rother, Doerte
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- Modularized Biocatalysis: Immobilization of Whole Cells for Preparative Applications in Microaqueous Organic Solvents
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The use of whole-cell biocatalysts enables catalyst application in microaqueous reaction systems, in which the liquid phase consists of high substrate loadings in organic solvents, to enable access to high concentrations of easy-to-purify product. One current research focus is the modularization of single reaction steps to (i)enable flexible combinations into multi-step enzyme reactions, (ii)investigate ideal reaction conditions, and (iii)facilitate catalyst handling and recycling. Therefore, we published the easy-to-apply encapsulation of a lyophilized whole-cell catalyst in a polymeric membrane recently. These catalytic "teabags" were demonstrated to enable flexible catalyst combinations for multi-step reactions and excellent recyclability during repeated batch experiments. We now describe the applicability of these "teabags" on a larger scale by using the new SpinChem reactor and a classical stirred-tank reactor model. As an alternative, we investigate the described alginate entrapment approach and compare the results. The carboligation reaction towards (R)-benzoin, using lyophilized E.coli that enclose Pseudomonas fluorescens benzaldehyde lyase (EC 4.1.2.38), served as a model reaction. It was demonstrated that the catalytic "teabags" are scalable and perform equally on the investigatory 5mL scale and the preparative 140mL reactor scale. Tested in a more advanced application, the "teabags" were proven to be useful in a one-pot two-step reaction for the gram-scale production of 1-phenylpropane-1,2-diol by using the SpinChem reactor, which allowed to reach an industrially relevant product concentration (32.9g L-1) and space-time yield (8.2g L-1 d-1).
- Wachtmeister, Jochen,Mennicken, Philip,Hunold, Andreas,Rother, D?rte
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- Whole-cell teabag catalysis for the modularisation of synthetic enzyme cascades in micro-aqueous systems
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Combining enzymes to form multi-step enzyme cascades has great potential to replace existing chemical routes with high atom-efficient and eco-efficient synthesis strategies as well as to grant access to new products, especially those with multi-stereogenic centres. However, easy solutions and tools for setting up appropriate reaction conditions and process modes are hardly available. The utilisation of teabags filled with whole cells has several advantages, such as 1) simplified handling and recovery of catalyst, 2) easy combination of various catalysts from catalyst toolboxes, 3) fast testing of different operating modes during cascadation and 4) simplified downstream processing. One of the main advantages is that lyophilised whole-cell catalysts can be applied in micro-aqueous media, allowing high substrate loads (also of poorly water-soluble substrates) and concomitantly enabling high catalyst stability. This was demonstrated herein for a synthetic two-step cascade towards chiral 1,2-diols starting from cheap aldehydes. The carboligation of two aldehydes using Pseudomonas fluorescens benzaldehyde lyase and subsequent oxidoreduction with Ralstonia sp. alcohol dehydrogenase yielded 1-phenylpropane-1,2-diol [(1R,2R)-PPD] in concentrations of up to 339 mM and excellent enantiomeric and diastereomeric excesses >99 %. Therefore, the combination of whole-cell catalysis and teabag modularisation allows cheap, easy-to-apply and efficient catalyst preparation to test enzyme combinations and optimal reaction conditions up to the preparative scale. By circumventing catalyst purification and immobilisation, and enabling high substrate loadings compared to those in aqueous systems, efficient production of a chiral diol with extraordinarily high product concentrations can be achieved. Biocatalysis in teabags: For the modularization of synthetic enzyme cascades, teabag-like containers are filled with lyophilised whole-cell catalyst. The bags are tight, recyclable, and easy-to-prepare and handle. Applied in a micro-aqueous system enabling high substrate loadings, stereoselective synthesis of diols was accomplished with high product concentrations and simplified catalyst and product separation.
- Wachtmeister, Jochen,Jakoblinnert, Andre,Kulig, Justyna,Offermann, Heike,Rother, Doerte
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- Enzymatic synthesis of all stereoisomers of 1-phenylpropane-1,2-diol
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A stereoselective two-step enzymatic synthesis of all four stereoisomers of 1-phenylpropane-1,2-diol starting from benzaldehyde and acetaldehyde is described. By using one of four possible combinations of a lyase followed by an alcohol dehydrogenase, each diol is accessible separately.
- Kihumbu,Stillger,Hummel,Liese
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- Enantioselective, Stereoconvergent Resolution Copolymerization of Racemic cis-Internal Epoxides and Anhydrides
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Unprecedented enantioselective resolution copolymerization of racemic cis-internal epoxides and anhydrides was mediated by dinuclear aluminum complexes with multiple chirality, affording optically active polyesters with two contiguous stereogenic centers, and the unreacted substrates in good enantioselectivity. Unexpected stereoconvergence is observed in this resolution copolymerization, where the selectivity factor for the enantioselective formation of copolymer significantly exceeds the kinetic resolution coefficient based on the unreacted epoxide at various conversions. Catalytic activity and copolymer enantioselectivity are strongly influenced by the phenolate ortho-substituents of the ligand set, as well as the axial linker and its chirality. An enantiopure binaphthol-linked bimetallic AlIII complex allows stereoconvergent access to the stereoregular semi-crystalline polyesters and a concomitant kinetic resolution of the epoxide substrates.
- He, Guang-Hui,Ren, Bai-Hao,Chen, Shi-Yu,Liu, Ye,Lu, Xiao-Bing
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supporting information
p. 5994 - 6002
(2021/02/11)
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- Synthesis of α-hydroxy ketones and vicinal (R, R)-diols by Bacillus clausii DSM 8716T butanediol dehydrogenase
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α-hydroxy ketones (HK) and 1,2-diols are important building blocks for fine chemical synthesis. Here, we describe the R-selective 2,3-butanediol dehydrogenase from B. clausii DSM 8716T (BcBDH) that belongs to the metal-dependent medium chain dehydrogenases/reductases family (MDR) and catalyzes the selective asymmetric reduction of prochiral 1,2-diketones to the corresponding HK and, in some cases, the reduction of the same to the corresponding 1,2-diols. Aliphatic diketones, like 2,3-pentanedione, 2,3-hexanedione, 5-methyl-2,3-hexanedione, 3,4-hexanedione and 2,3-heptanedione are well transformed. In addition, surprisingly alkyl phenyl dicarbonyls, like 2-hydroxy-1-phenylpropan-1-one and phenylglyoxal are accepted, whereas their derivatives with two phenyl groups are not substrates. Supplementation of Mn2+ (1 mM) increases BcBDH's activity in biotransformations. Furthermore, the biocatalytic reduction of 5-methyl-2,3-hexanedione to mainly 5-methyl-3-hydroxy-2-hexanone with only small amounts of 5-methyl-2-hydroxy-3-hexanone within an enzyme membrane reactor is demonstrated.
- Bongaerts, Johannes,Jablonski, Melanie,Kipp, Carina Ronja,Molinnus, Denise,Muschallik, Lukas,Pohl, Martina,Sch?ning, Michael J.,Selmer, Thorsten,Siegert, Petra,Wagner, Torsten
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p. 12206 - 12216
(2020/04/20)
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- Regio- and stereoselective multi-enzymatic aminohydroxylation of β-methylstyrene using dioxygen, ammonia and formate
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We report an enzymatic route for the formal regio- and stereoselective aminohydroxylation of β-methylstyrene that consumes only dioxygen, ammonia and formate; carbonate is the by-product. The biocascade entails highly selective epoxidation, hydrolysis and hydrogen-borrowing alcohol amination. Thus, β-methylstyrene was converted into 1R,2R and 1S,2R-phenylpropanolamine in 59-63% isolated yields, and up to >99.5 : 0.5 dr and er.
- Corrado, Maria L.,Knaus, Tanja,Mutti, Francesco G.
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supporting information
p. 6246 - 6251
(2019/12/03)
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- Syn-dihydroxylation of alkenes using a sterically demanding cyclic diacyl peroxide
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The syn-dihydroxylation of alkenes is a highly valuable reaction in organic synthesis. Cyclic acyl peroxides (CAPs) have emerged recently as promising candidates to replace the commonly employed toxic metals for this purpose. Here, we demonstrate that the structurally demanding cyclic peroxide spiro[bicyclo[2.2.1]heptane-2,4′-[1,2]dioxolane]-3′,5′-dione (P4) can be effectively used for the syn-dihydroxylation of alkenes. Reagent P4 also shows an improved selectivity for dihydroxylation of alkenes bearing β-hydrogens as compared to other CAPs, where both diol and allyl alcohol products compete with each other. Furthermore, the use of enantiopure P4 (labeled P4′) demonstrates the potential of P4′ for a metal-free asymmetric syn-dihydroxylation of alkenes.
- Pilevar, Afsaneh,Hosseini, Abolfazl,Becker, Jonathan,Schreiner, Peter R.
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p. 12377 - 12386
(2019/10/11)
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- An Enzymatic 2-Step Cofactor and Co-Product Recycling Cascade towards a Chiral 1,2-Diol. Part I: Cascade Design
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Alcohol dehydrogenases are of high interest for stereoselective syntheses of chiral building blocks such as 1,2-diols. As this class of enzymes requires nicotinamide cofactors, their application in biotechnological synthesis reactions is economically only feasible with appropriate cofactor regeneration. Therefore, a co-substrate is oxidized to the respective co-product that accumulates in equal concentration to the desired target product. Co-product removal during the course of the reaction shifts the reaction towards formation of the target product and minimizes undesired side effects. Here we describe an atom efficient enzymatic cofactor regeneration system where the co-product of the ADH is recycled as a substrate in another reaction set. A 2-step enzymatic cascade consisting of a thiamine diphosphate (ThDP)-dependent carboligase and an alcohol dehydrogenase is presented here as a model reaction. In the first step benzaldehyde and acetaldehyde react to a chiral 2-hydroxy ketone, which is subsequently reduced by to a 1,2-diol. By choice of an appropriate co-substrate (here: benzyl alcohol) for the cofactor regeneration in the alcohol dehydrogenases (ADH)-catalyzed step, the co-product (here: benzaldehyde) can be used as a substrate for the carboligation step. Even without any addition of benzaldehyde in the first reaction step, this cascade design yielded 1,2-diol concentrations of >100 mM with optical purities (ee, de) of up to 99%. Moreover, this approach overcomes the low benzaldehyde solubility in aqueous systems and optimizes the atom economy of the reaction by reduced waste production. The example presented here for the 2-step recycling cascade of (1R,2R)-1-phenylpropane-1,2-diol can be applied for any set of enzymes, where the co-products of one process step serve as substrates for a coupled reaction. (Figure presented.).
- Kulig, Justyna,Sehl, Torsten,Mackfeld, Ursula,Wiechert, Wolfgang,Pohl, Martina,Rother, D?rte
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supporting information
p. 2607 - 2615
(2019/05/24)
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- Atroposelective Synthesis of PINAP via Dynamic Kinetic Asymmetric Transformation
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The atroposelective synthesis of PINAP ligands has been accomplished via a palladium-catalyzed C?P coupling process through dynamic kinetic asymmetric transformation. These catalytic conditions allow access to a wide variety of alkoxy- and benzyloxy-substituted PINAP ligands in high enantiomeric excess. The methods described in this communication afford valuable P,N ligands in good yields and high enantioselectivity using low catalyst loading. (Figure presented.).
- Han, Seo-Jung,Bhat, Vikram,Stoltz, Brian M.,Virgil, Scott C.
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p. 441 - 444
(2018/12/14)
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- Cis -Oxoruthenium complexes supported by chiral tetradentate amine (N4) ligands for hydrocarbon oxidations
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We report the first examples of ruthenium complexes cis-[(N4)RuIIICl2]+ and cis-[(N4)RuII(OH2)2]2+ supported by chiral tetradentate amine ligands (N4), together with a high-valent cis-dioxo complex cis-[(N4)RuVI(O)2]2+ supported by the chiral N4 ligand mcp (mcp = N,N′-dimethyl-N,N′-bis(pyridin-2-ylmethyl)cyclohexane-1,2-diamine). The X-ray crystal structures of cis-[(mcp)RuIIICl2](ClO4) (1a), cis-[(Me2mcp)RuIIICl2]ClO4 (2a) and cis-[(pdp)RuIIICl2](ClO4) (3a) (Me2mcp = N,N′-dimethyl-N,N′-bis((6-methylpyridin-2-yl)methyl)cyclohexane-1,2-diamine, pdp = 1,1′-bis(pyridin-2-ylmethyl)-2,2′-bipyrrolidine)) show that the ligands coordinate to the ruthenium centre in a cis-α configuration. In aqueous solutions, proton-coupled electron-transfer redox couples were observed for cis-[(mcp)RuIII(O2CCF3)2]ClO4 (1b) and cis-[(pdp)RuIII(O3SCF3)2]CF3SO3 (3c′). Electrochemical analyses showed that the chemically/electrochemically generated cis-[(mcp)RuVI(O)2]2+ and cis-[(pdp)RuVI(O)2]2+ complexes are strong oxidants with E° = 1.11-1.13 V vs. SCE (at pH 1) and strong H-atom abstractors with DO-H = 90.1-90.8 kcal mol-1. The reaction of 1b or its (R,R)-mcp counterpart with excess (NH4)2[CeIV(NO3)6] (CAN) in aqueous medium afforded cis-[(mcp)RuVI(O)2](ClO4)2 (1e) or cis-[((R,R)-mcp)RuVI(O)2](ClO4)2 (1e?), respectively, a strong oxidant with E(RuVI/V) = 0.78 V (vs. Ag/AgNO3) in acetonitrile solution. Complex 1e oxidized various hydrocarbons, including cyclohexane, in acetonitrile at room temperature, affording alcohols and/or ketones in up to 66% yield. Stoichiometric oxidations of alkenes by 1e or 1e? in tBuOH/H2O (5:1 v/v) afforded diols and aldehydes in combined yields of up to 98%, with moderate enantioselectivity obtained for the reaction using 1e?. The cis-[(pdp)RuII(OH2)2]2+ (3c)-catalysed oxidation of saturated C-H bonds, including those of ethane and propane, with CAN as terminal oxidant was also demonstrated.
- Tse, Chun-Wai,Liu, Yungen,Wai-Shan Chow, Toby,Ma, Chaoqun,Yip, Wing-Ping,Chang, Xiao-Yong,Low, Kam-Hung,Huang, Jie-Sheng,Che, Chi-Ming
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p. 2803 - 2816
(2018/03/21)
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- Semirational Engineering of the Naphthalene Dioxygenase from Pseudomonas sp. NCIB 9816-4 towards Selective Asymmetric Dihydroxylation
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Enzyme-catalyzed asymmetric dihydroxylation is a powerful tool for the selective oxyfunctionalization of various organic compounds. By applying Rieske non-heme dioxygenases (ROs), molecular oxygen and a reduction equivalent are needed for the generation of vicinal cis-diols. We report a comprehensive mutagenesis study of the active site of the naphthalene dioxygenase from Pseudomonas sp. NCIB 9816-4 comprising 62 variants. We aimed to understand the important structure–function relationships by investigating different substituted arene substrates and the geometry of the active site. Introducing single-point mutations at positions F202, A206, V260, H295, F352, and L307 resulted in drastic shifts in the reaction specificity, regioselectivity, and stereoselectivity (≥90 %) while maintaining the residual activity towards the natural substrate naphthalene.
- Halder, Julia M.,Nestl, Bettina M.,Hauer, Bernhard
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p. 178 - 182
(2017/12/26)
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- Chiral-Substituted Poly-N-vinylpyrrolidinones and Bimetallic Nanoclusters in Catalytic Asymmetric Oxidation Reactions
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A new class of poly-N-vinylpyrrolidinones containing an asymmetric center at C5 of the pyrrolidinone ring were synthesized from l-amino acids. The polymers, particularly 17, were used to stabilize nanoclusters such as Pd/Au for the catalytic asymmetric oxidations of 1,3- and 1,2-cycloalkanediols and alkenes, and Cu/Au was used for C-H oxidation of cycloalkanes. It was found that the bulkier the C5 substituent in the pyrrolidinone ring, the greater the optical yields produced. Both oxidative kinetic resolution of (±)-1,3- and 1,2-trans-cycloalkanediols and desymmetrization of meso cis-diols took place with 0.15 mol % Pd/Au (3:1)-17 under oxygen atmosphere in water to give excellent chemical and optical yields of (S)-hydroxy ketones. Various alkenes were oxidized with 0.5 mol % Pd/Au (3:1)-17 under 30 psi of oxygen in water to give the dihydroxylated products in >93% ee. Oxidation of (R)-limonene at 25 °C occurred at the C-1,2-cyclic alkene function yielding (1S,2R,4R)-dihydroxylimonene 49 in 92% yield. Importantly, cycloalkanes were oxidized with 1 mol % Cu/Au (3:1)-17 and 30% H2O2 in acetonitrile to afford chiral ketones in very good to excellent chemical and optical yields. Alkene function was not oxidized under the reaction conditions. Mechanisms were proposed for the oxidation reactions, and observed stereo- and regio-chemistry were summarized.
- Hao, Bo,Gunaratna, Medha J.,Zhang, Man,Weerasekara, Sahani,Seiwald, Sarah N.,Nguyen, Vu T.,Meier, Alex,Hua, Duy H.
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supporting information
p. 16839 - 16848
(2017/01/10)
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- Production Of Enantiopure alpha-Hydroxy Carboxylic Acids From Alkenes By Cascade Biocatalysis
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The invention provides compositions comprising an alkene epoxidase and a selective epoxide hydrolase, such as a recombinant microorganism comprising a first heterologous nucleic acid encoding an alkene epoxidase and a second heterologous nucleic acid encoding a selective epoxide hydrolase. Exemplary alkene epoxidases include StyAB, while exemplary selective epoxide hydrolases include epoxide hydrolases from Sphingomonas, Solanum tuberosum, or Aspergillus. The invention also provides non-toxic methods of making enantiomerically pure vicinal diols or enantiomerically pure alpha-hydroxy carboxylic acids using these compositions and microorganisms.
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Paragraph 0094-0096
(2016/05/02)
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- Highly Enantioselective Iron-Catalyzed cis-Dihydroxylation of Alkenes with Hydrogen Peroxide Oxidant via an FeIII-OOH Reactive Intermediate
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The development of environmentally benign catalysts for highly enantioselective asymmetric cis-dihydroxylation (AD) of alkenes with broad substrate scope remains a challenge. By employing [FeII(L)(OTf)2] (L=N,N′-dimethyl-N,N′-bis(2-methyl-8-quinolyl)-cyclohexane-1,2-diamine) as a catalyst, cis-diols in up to 99.8 % ee with 85 % isolated yield have been achieved in AD of alkenes with H2O2as an oxidant and alkenes in a limiting amount. This “[FeII(L)(OTf)2]+H2O2” method is applicable to both (E)-alkenes and terminal alkenes (24 examples >80 % ee, up to 1 g scale). Mechanistic studies, including18O-labeling, UV/Vis, EPR, ESI-MS analyses, and DFT calculations lend evidence for the involvement of chiral FeIII-OOH active species in enantioselective formation of the two C?O bonds.
- Zang, Chao,Liu, Yungen,Xu, Zhen-Jiang,Tse, Chun-Wai,Guan, Xiangguo,Wei, Jinhu,Huang, Jie-Sheng,Che, Chi-Ming
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supporting information
p. 10253 - 10257
(2016/08/24)
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- Regio- and enantioselective reduction of diketones: Preparation of enantiomerically pure hydroxy ketones catalysed by Candida parapsilosis ATCC 7330
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Enantiomerically enriched hydroxy ketones were prepared by the reduction of the corresponding diketones with excellent enantiomeric excess (98%) and in good yields (up to 75%) using whole cells of Candida parapsilosis ATCC 7330. Cyclic diketones, such as 1,2-cyclohexanedione and 1,4-cyclohexanedione, resulted in hydroxy ketones as products. Cyclohexane-1,3-dione and 5,5-dimethylcyclohexane-1,3-dione gave dimerised products, such as 2,2′-(ethane-1,1-diyl)bis(3-hydroxycyclohex-2-enone) and 2,2′-(ethane-1,1-diyl)bis(3-hydroxy-5,5-dimethylcyclohex-2-enone) with acetaldehyde generated in situ from whole cells of Candida parapsilosis ATCC 7330, which is reported here for the first time.
- Mahajabeen, Pula,Chadha, Anju
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p. 1167 - 1173
(2015/10/28)
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- Enantio- and diastereoselective synthesis of 1,2-hydroxyboronates through Cu-Catalyzed additions of alkylboronates to aldehydes
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The first catalytic enantio- and diastereoselective synthesis of 1,2-hydroxyboronates is reported. Reactions are promoted by a readily available chiral monodentate phosphoramidite-copper complex in the presence of an alkyl 1,1-diboron reagent. Products contain two contiguous stereogenic centers and are obtained in up to 91% yield, >98:2 d.r., and 98:2 e.r. The reaction is tolerant of aryl and vinyl aldehydes, and the 1,2-hydroxyboronate products can be transformed into versatile derivatives. Mechanistic experiments indicate control of absolute stereochemistry of the α-boryl component.
- Joannou, Matthew V.,Moyer, Brandon S.,Meek, Simon J.
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supporting information
p. 6176 - 6179
(2015/06/02)
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- Ionophilic imidazolium-tagged cinchona ligand on LDH-immobilized osmium: Recyclable and recoverable catalytic system for asymmetric dihydroxylation reaction of olefins
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Abstract A catalytic system for the asymmetric dihydroxylation of olefins was developed by using an ionic-tagged biscinchona alkaloid ligand immobilized onto OsO4-exchanged layered double hydroxide (LDH) as a robust recyclable homogenous-heterogeneous catalytic system. The desired products were obtained in high yield and enantioselectivity.
- Kaur, Amanpreet,Singh, Vasundhara
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p. 1191 - 1194
(2015/06/02)
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- Enantioselective trans-dihydroxylation of aryl olefins by cascade biocatalysis with recombinant escherichia coli coexpressing monooxygenase and epoxide hydrolase
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Cascade biocatalysis via intracellular epoxidation and hydrolysis was developed as a green and efficient method for enantioselective dihydroxylation of aryl olefins to prepare chiral vicinal diols in high ee and high yield. Escherichia coli (SSP1) coexpressing styrene monooxygenase (SMO) and epoxide hydrolase SpEH was developed as a simple and efficient biocatalyst for S-enantioselective dihydroxylation of terminal aryl olefins 1a-15a to give (S)-vicinal diols 1c-15c in high ee (97.5-98.6% for 10 diols; 92.2-93.9% for 3 diols) and high yield (91-99% for 6 diols; 86-88% for 2 diols; 67% for 3 diols). Combining SMO and epoxide hydrolase StEH showing complementary regioselectivity to SpEH as a biocatalyst for the cascade biocatalysis gave rise to R-enantioselective dihydroxylation of aryl olefins, being the first example of this kind of reversing the overall enantioselectivity of cascade biocatalysis. E. coli (SST1) coexpressing SMO and StEH was also engineered as a green and efficient biocatalyst for R-dihydroxylation of terminal aryl olefins 1a-15a to give (R)-vicinal diols 1c-15c in high ee (94.2-98.2% for 7 diols; 84.2-89.9% for 6 diols) and high yield (90-99% for 6 diols; 85-89% for 5 diols; 65% for 1 diol). E. coli (SSP1) and E. coli (SST1) catalyzed the trans-dihydroxylation of trans-aryl olefin 16a and cis-aryl olefin 17a with excellent and complementary stereoselectivity, giving each of the four stereoisomers of 1-phenyl-1,2- propanediol 16c in high ee and de, respectively. Both strains catalyzed the trans-dihydroxylation of aryl cyclic olefins 18a and 19a to afford the same trans-cyclic diols (1R,2R)-18c and (1R,2R)-19c, respectively, in excellent ee and de. This type of cascade biocatalysis provides a tool that is complementary to Sharpless dihydroxylation, accepting cis-alkene and offering enantioselective trans-dihydroxylation.
- Wu, Shuke,Chen, Yongzheng,Xu, Yi,Li, Aitao,Xu, Qisong,Glieder, Anton,Li, Zhi
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p. 409 - 420
(2014/03/21)
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- Regio- and enantio-selective oxidation of diols by Candida parapsilosis ATCC 7330
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Selectivity between primary and secondary alcohols was observed in oxidation using whole cells of Candida parapsilosis ATCC 7330, where the secondary alcohol was preferentially oxidized. In racemic sec alcohols, the 'R' enantiomer was selectively oxidized to the corresponding keto alcohol (yield = 18-54%) leaving the 'S' diol (yield = 31-69% and enantiomeric excess from 14% to >99%). A biphasic system consisting of isooctane-water (48 : 2 v/v) was used as a medium for biotransformation at 25 °C. This is the first report of the regio- and enantio-selective oxidation of diols using C. parapsilosis ATCC 7330.
- Sivakumari, Thakkellapati,Chadha, Anju
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p. 60526 - 60533
(2015/02/19)
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- Stereoselective reduction of 2-hydroxy ketones towards syn- and anti-1,2-diols
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Stereoselective reduction of 2-hydroxy ketones should in principle give access to syn- and anti-1,2-diols. anti-1,2-Diols are accessible in a highly selective way using zinc borohydride [Zn(BH4)2] under chelation control (dr>20:1). Diastereoselective reduction of unprotected or even protected 2-hydroxy ketones towards syn-1,2-diols could be achieved only with moderate selectivity of dr≤5:1. Even when using sterically demanding protecting groups and/or polymer-supported borohydride reagents high selectivity could not be achieved. A new ionic liquid-dependent borohydride reduction method, although highly attractive with respect to reaction engineering, resulted in only moderate to good selectivity. An efficient two-step biocatalytic method for the synthesis of syn-1,2-diols is described. The method relies on the whole-cell Pichia glucozyma-catalyzed stereoselective reduction of the unprotected (R)-2-hydroxy ketones (dr>10:1). The latter are accessible through thiamine diphosphate-dependent enzyme-catalyzed synthesis starting from simple aldehydes. Thus, biocatalytic transformations enable a process which is hardly accessible through present non-enzymatic methods. Copyright
- Husain, Syed Masood,Stillger, Thomas,Duenkelmann, Pascal,Loedige, Melanie,Walter, Lydia,Breitling, Elke,Pohl, Martina,Buerchner, Mara,Krossing, Ingo,Mueller, Michael,Romano, Diego,Molinari, Francesco
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p. 2359 - 2362
(2011/10/19)
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- Modular monodentate oxaphospholane ligands: Utility in highly efficient and enantioselective 1,4-diboration of 1,3-dienes
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Tune it up! Tunable, chiral, monodentate oxaphospholane ligands (termed OxaPhos) are highly effective in the Pt-catalyzed title reaction, providing the 1,4-addition products in enantiomer ratios approaching 99:1 (see scheme). In the presence of enantiomerically pure cis-iBu-OxaPhos, a catalyst loading of only 0.02 mol% [Pt(dba)3] was sufficient for effective reaction. pin=pinacolato, dba=dibenzylideneacetone.
- Schuster, Christopher H.,Li, Bo,Morken, James P.
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p. 7906 - 7909
(2011/10/09)
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- Access to enantiopure aromatic epoxides and diols using epoxide hydrolases derived from total biofilter DNA
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Metagenomic DNA is a rich source of genes encoding novel epoxide hydrolases (EHs). We retrieved two genes encoding functional EHs from total DNA isolated from biofilter-derived biomass, using PCR with EH-specific degenerate primers followed by genome-walking PCR. The degenerate primers were based on two EH-specific consensus sequences: HGWP and GHDWG. The resulting recombinant EHs, Kau2 and Kau8, were expressed in Escherichia coli, and their enantioselectivity and regioselectivity were determined using 13 different epoxide substrates. The EH Kau2 had broad substrate specificity and preferentially hydrolyzed epoxides with S-configuration. It showed high enantioselectivity towards aromatic epoxides such as styrene oxide, p-nitrostyrene oxide, and trans-1-phenyl-1,2-epoxypropane. In addition, Kau2 showed enantioconvergent hydrolysis activity. The EH Kau8 also showed broad substrate specificity and preferentially hydrolyzed epoxides with R-configuration. High enantioselectivity was observed for p-nitrostyrene oxide, and the hydrolysis activity of Kau8 was less enantioconvergent than that of Kau2. To determine the usefulness of Kau2 for synthetic applications, preparative-scale biohydrolysis reactions were performed. Specifically, two kinetic resolutions were carried out with 80 g/L of racemic trans-1-phenyl-1,2-epoxypropane, affording both (1R,2R)-epoxide and the corresponding (1R,2S)-diol in high enantiomeric excess (>99%) and good yield (>45%). In addition, a process based on enantioconvergent hydrolysis by the EH Kau2 was established for racemic cis-1-phenyl-1,2-epoxypropane at a concentration of 13 g/L, resulting in the formation of the corresponding (1R,2R)-diol with a 97% yield and an enantiomeric excess exceeding 98%.
- Kotik, Michael,Stepanek, Vaclav,Grulich, Michal,Kyslik, Pavel,Archelas, Alain
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experimental part
p. 41 - 48
(2010/12/19)
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- Enantioselective hydrogenation of 1-phenyl-1,2-propanodione on Pt/ ZrO 2 catalysts
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The enantioselective hydrogenation of 1-phenyl-1,2-propanedione at 298K and pressure of 40 bar of H2 over zirconia supported Pt catalysts has been studied. Three different zirconia were prepared: i) ZrO2- P obtained by a precipitation procedure from ZrOCl2 ii) MSZrO 2 obtained by a sol-gel procedure using cetryltrimethylammonium bromide (CTMABR) as surfactant to get a mesostructured solid iii) CNTsZrO 2 obtained after impregnation of carbon nanotubes with ZrO(NO) 3 followed by pyrolisis and calcination. Pt (1wt%) was introduced on the support by impregnation of an aqueous solution of H2PtCl 6. The catalysts were characterized by nitrogen adsorption-desorption isotherms at 77 K, hydrogen chemisorption, XRD and TEM techniques. The reactions were carried out in a stainless steel batch reactor using cyclohexane as solvent and cinchonidine as chiral modifier. The presence of CD in the reaction medium is necessary to induce an enantiomeric excess (ee) of the desired product R-1phenyl-1 hydroxi-2-propanone. In all the studied systems, the relation between the enantioselectivity and the CD concentration added in situ exhibits a bell type curve; indicative of the importance of competitive adsorption between the modifier and the substrate on the catalyst surface. On the other hand, confinement effect led to an important enhancement in the activity in those catalysts supported on mesostructured supports, mainly in the Pt/CNTsZrO2 catalyst.
- Urbina, Claudia,Pecchi, Gina,Campos, Cristian,Reyes, Patricio
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experimental part
p. 25 - 30
(2010/09/05)
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- A recyclable dendritic osmium catalyst for homogeneous dihydroxylation of olefins
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A series of osmate (OsO42-) core dendrimers was prepared by an ion-exchange technique through the mixing of K 2OsO4 and a bis(quaternary ammonium bromide) core dendrimer, which consisted of poly(benzyl ether) dendron. By employing an osmate core dendrimer as a homogeneous catalyst, dihydroxylation reactions of olefins proceeded rapidly, and the dendritic osmium catalyst was recovered by reprecipitation and then reused. Furthermore, a dendritic effect on the recyclability of a catalyst was observed. In the case of asymmetric dihydroxylation reactions, the corresponding diol was obtained in a high chemical yield with a fair enantiomeric excess (ee). In this case, not only the dendritic osmium catalyst but also the chiral ligand could be recovered by reprecipitation and reused efficiently up to five times.
- Fujita, Ken-Ichi,Yamazaki, Manabu,Ainoya, Taku,Tsuchimoto, Teruhisa,Yasuda, Hiroyuki
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experimental part
p. 8536 - 8543
(2010/11/18)
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- Hydrogenation of 1-phenyl-1,2-propanedione over Pt catalysts modified by cinchona alkaloid O-ethers and the kinetic resolution of the 1-hydroxyketones generated
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Nine cinchona alkaloid O-ethers together with cinchonidine and cinchonine were studied as chiral modifiers in the enantioselective hydrogenation of 1-phenyl-1,2-propanedione over Pt/Al2O3. The influence of the O-substituent on the reaction rate, selectivity and product distribution was investigated. Apparent rate constants for all hydrogenation steps were calculated using a first-order kinetic approach resulting in a good agreement between the experimentally recorded and predicted concentrations. The experimentally observed structure-selectivity effects indicate that the mechanisms of enantiodifferentiation over the catalyst modified by parent cinchona alkaloids and their ether derivatives differ from each other. Moreover, the modifier structure-selectivity dependence and the solvent effect were different for enantio- and diastereoselection in the 1-phenyl-1,2-propanedione and 1-hydroxyketone hydrogenations. Correlation between the modifier substituent bulkiness and diastereoselectivity of the 1-hydroxyketone hydrogenation was observed. Data on the inversion of enantioselectivity of 1-phenyl-1,2-propanedione hydrogenation, diastereoselectivity and the sense of kinetic resolution of the 1-hydroxyketones were presented. Due to the complexity of the reaction network, several competing mechanistic pathways may be present in a single reaction system.
- Busygin, Igor,Waerna, Johan,Toukoniitty, Esa,Murzin, Dmitry Yu.,Leino, Reko
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p. 339 - 348
(2008/09/20)
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- Osmium-catalyzed asymmetric dihydroxylation by carbon dioxide-activated hydrogen peroxide and N-methylmorpholine
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An improved process has been developed for the osmium-catalyzed dihydroxylation of olefins via in situ formation of NMO from NMM using CO2 catalysis and H2O2. All olefins examined were selectively cis-dihydroxylated to their corresponding diols in good to excellent yields, and by the use of chiral ligands, high enantiomeric excesses were obtained.
- Balagam, Bharathi,Mitra, Ranjan,Richardson, David E.
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p. 1071 - 1075
(2008/09/18)
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- A microwave-enhanced, lewis acid-catalyzed synthesis of 1,3-dioxolanes and oxazolines from epoxides
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A fast and highly regio- and stereoselective transformation of non-conventional β-lactam- b containing epoxides into the corresponding cyclic 1,3-dioxolanes and oxazolines is herein reported, using microwave irradiation as an efficient source of energy, in the presence of stoichiometric or catalytic amounts of Lewis acids, without an additional solvent. These cyclic compounds are the protected forms of diols and amino alcohols.
- Benfatti, Fides,Cardillo, Giuliana,Gentilucci, Luca,Tolomelli, Alessandra,Monari, Magda,Piccinelli, Fabio
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p. 1256 - 1264
(2008/09/17)
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- Highly stereoselective syn-ring opening of enantiopure epoxides with nitric oxide
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Reaction of enantiopure epoxides (1) with NO occurred highly stereoselectively, affording syn-ring opened products, nitrates (2). The configuration of 2 was confirmed to be retained by determining the configuration of reduced products 1,2-glycols (4) from 2. A possible mechanism is suggested to trace out the syn-ring opening pathway.
- Wu, Wentao,Liu, Qiang,Shen, Yinglin,Li, Rui,Wu, Longmin
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p. 1653 - 1656
(2008/02/03)
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- Preparation, characterization and catalytic properties of polyaniline-supported metal complexes
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Polyaniline-supported Sc, In, Pd, Os and Re catalysts were prepared by using a simple protocol and the thus prepared catalysts were well characterized using FTIR, XPS, UV-Vis/DRS, TGA-DTA. All the catalysts were successfully employed in a wide range of organic transformations such as cyanation and allylation of carbonyl compound, Suzuki coupling of aryl halides and boronic acids, and, most importantly, in asymmetric dihydroxylation of olefins to afford optically active vicinal diols. All the catalysts were separated from the reaction mixture by simple filtration and reused with consistent activity for five cycles without noticeable leaching of metal from the support.
- Choudary, Boyapati M.,Roy, Moumita,Roy, Sarabindu,Kantam, M. Lakshmi,Sreedhar, Bojja,Kumar, Karasala Vijay
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p. 1734 - 1742
(2007/10/03)
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- CATALYZED ENANTIOSELECTIVE TRANSFORMATION OF ALKENES
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Enantioselective catalytic reactions that operate directly on unactivated alkenes for the preparation of chiral organic building blocks and new materials. More particularly, a catalyzed enantioselective reaction that operates on an unsaturated hydrocarbon, such as an alkene, to provide an enantiomerically enriched reactive organometallic intermediate, which can be converted to a variety of multifunctional optically active reaction products.
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Page/Page column 50
(2010/02/10)
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- Concatenated catalytic asymmetric allene diboration/allylation/ functionalization
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(Chemical Equation Presented) Palladium-catalyzed enantioselective diboration of prochiral allenes generates a reactive chiral allylboron intermediate which is a versatile reagent for the allylation of carbonyls. Experiments that improve the enantioselectivity of this process, examine the substrate scope, and are directed toward functionalization of the allylation intermediate are described.
- Woodward, Angela R.,Burks, Heather E.,Chan, Louis M.,Morken, James P.
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p. 5505 - 5507
(2007/10/03)
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- Markedly enhanced recyclability of osmium catalyst in asymmetric dihydroxylation reactions by using macroporous resins bearing both residual vinyl groups and quaternary ammonium moieties
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Markedly enhanced recyclability of osmium catalyst in asymmetric dihydroxylation has been achieved by using osmylated macroporous resins bearing both residual vinyl groups and quaternary ammonium moiety. The Royal Society of Chemistry 2005.
- Kim, Kwang Jin,Choi, Han Young,Hwang, Soon Ho,Park, Yil Sung,Kwueon, Eun Kyung,Choi, Doo Seong,Song, Choong Eui
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p. 3337 - 3339
(2007/10/03)
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- An electrophilic cleavage procedure for the asymmetric dihydroxylation: Direct enantioselective synthesis of cyclic boronic esters from olefins
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A variation within the osmium-catalysed asymmetric dihydroxylation (AD) of olefins is described that yields cyclic boronic esters from olefins in a straight-forward manner. This process represents the first real product alteration in asymmetric dihydroxylation, since all previous protocols lead to free diols exclusively. A protocol based on the Sharpless AD conditions (for enantioselective oxidation of prochiral olefins) was developed that gives cyclic boronic esters with excellent enantiomeric excesses (ee's). Some of the ee's are higher than those reported for conventional AD. The unprecedented role of phenyl boronic acid on the course of the AD reaction was investigated in detail. PhB(OH)2 does not interfere with the chiral ligand. leaving the enantioselective step of olefin oxidation intact. The main role of the boronic acids - apart from protecting the diol products against potential overoxidation-relies on removing the diol entity in an electrophilic cleavage, which is in contrast to the conventional hydrolylic cleavage of the AD protocols. Thus, a mechanistically new cleavage for enantioselective dihydroxylation reactions is introduced within the present work.
- Hoevelmann, Claas H.,Muniz, Kilian
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p. 3951 - 3958
(2007/10/03)
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- Rh-catalyzed enantioselective diboration of simple alkenes: Reaction development and substrate scope
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The rhodium-catalyzed reaction between bis(catecholato)diboron and simple alkenes results in the syn addition of the diboron across the alkene. The resulting 1,2-bis(boronate) is subsequently oxidized to provide the 1,2-diol. In the presence of enantiomerically enriched Quinap ligand, high enantioselection in the diboration can be achieved. The reaction is highly selective for trans- and trisubstituted alkenes and can be selective for some monosubstituted alkenes as well. The development of this reaction is described as is the substrate scope and experiments that are informative about the reaction mechanism and competing pathways.
- Trudeau, Stephane,Morgan, Jeremy B.,Shrestha, Mohanish,Morken, James P.
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p. 9538 - 9544
(2007/10/03)
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- A novel microencapsulated osmium catalyst using cross-linked polystyrene as an efficient catalyst for asymmetric dihydroxylation of olefins in water
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A novel microencapsulated osmium catalyst (PSresin-MC Os) was developed using cross-linked polystyrene. The concept of this method may go beyond that of microencapsulation. The catalyst was successfully used in asymmetric dihydroxylation in water, and it was recovered quantitatively by simple filtration and reused several times without loss of activity. The shape of the catalyst was maintained even after several uses. Moreover, no leaching of the Os component was detected.
- Ishida, Tasuku,Akiyama, Ryo,Kobayashi, Shu
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p. 1189 - 1192
(2007/10/03)
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- Polysiloxane-bound ligand accelerated catalysis: A modular approach to heterogeneous and homogeneous macromolecular asymmetric dihydroxylation ligands
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Polysiloxane acts as a modular scaffold for macromolecular reagent development. Two separate components were covalently integrated into one material, one constituent provided reagent functionality, the other modulated solubility. In particular cinchona alkaloid based ligands used in the osmium tetroxide catalyzed asymmetric dihydroxylation (AD) reaction were covalently attached to commercially available polysiloxane. To enhance the reactivity of these polymeric ligands, multifunctional reagents were designed to include both the cinchona alkaloid and an alkoxyethylester solubilizing moiety providing random co-polymers. While the mono-functional materials led to heterogeneous conditions, the bifunctional polymers resulted in homogeneous reaction mixtures. Although both reagent types provided diol products with excellent yield and selectivity (>99% ee in nearly quantitative yield) the homogeneous analog has nearly twice the reactivity. Every repeat unit in the heterogeneous material was functionalized along the polysiloxane backbone while approximately half of these sites contained ligand in the homogeneous version. This approach led to macromolecular catalysts with high loadings of ligand and therefore materials with very low equivalent weights. Although these polymers are highly loaded they do maintain reactivity on a par with their free ligand counterpart. Using straightforward purification techniques (i.e. precipitation, simple filtration, or ultrafiltration) these polymeric ligands were easily separated from diol product and reused multiple times. Polysiloxane is a viable support for the catalysis of AD reactions and may provide a generally useful backbone for other catalytic systems.
- DeClue, Michael S.,Siegel, Jay S.
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p. 2287 - 2298
(2007/10/03)
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- A triazine core for a new class of Sharpless asymmetric dihydroxylation ligands
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Sharpless asymmetric dihydroxylation ligands were synthesized using a triazine spacer group in two, high yielding steps and gave good enantioselectivities in the asymmetric dihydroxylation of alkenes. Sharpless asymmetric dihydroxylation ligands were synthesized using a triazine spacer group in two, high yielding steps from cheap, readily available starting materials. The ligands, gave good enantioselectivities in the asymmetric dihydroxylation of alkenes and may provide a very economic alternative to current systems.
- McNamara, Catherine Anne,King, Frank,Bradley, Mark
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p. 8527 - 8529
(2007/10/03)
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- Supported osmates, process for preparation thereof, and a process for the preparation of chiral vicinal diols using supported osmate catalyst
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The present invention provides a supported osmate useful as a reusable catalyst in the preparation of vicinal diols. The present invention also relates to a process for the preparation of supported osmates of the formula (S—NR3)2OsO4.nH2O wherein S is a support, R is an alkyl group, n is the number of water molecules and use thereof in the preparation of vicinal diols by asymmetric dihydroxylation (AD) of olefins in presence of cinchona alkaloid compounds.
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-
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- Supported osmates, process for preparation thereof, and a process for the preparation of chiral vicinal diols using supported osmate catalyst
-
The present invention provides a supported osmate useful as a reusable catalyst in the preparation of vicinal diols. The present invention also relates to a process for the preparation of supported osmates of the formula (S—NR3)2OsO4.nH2O wherein S is a support, R is an alkyl group, n is the number of water molecules and use thereof in the preparation of vicinal diols by asymmetric dihydroxylation (AD) of olefins in presence of cinchona alkaloid compounds.
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- A trifunctional catalyst for one-pot synthesis of chiral diols via heck coupling-N-oxidation-asymmetric dihydroxylation: Application for the synthesis of diltiazem and taxol side chain
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A heterogeneous bifunctional catalyst composed of OsO42--WO42- and a trifunctional catalyst comprising PdCl42--OsO42-- WO42-, designed and prepared by an ion-exchange technique using layered double hydroxides (LDH) as an ion-exchanger and their homogeneous bifunctional analogue, K2OsO4-Na2WO4 and trifunctional analogue, Na2PdCl4-K2OsO4-K2 OSO4-NNa2WO4, devised for the first time are evaluated for the synthesis of chiral vicinal diols. These bifunctional and trifunctional catalysts perform asymmetric dihydroxylation-N-oxidation and Heck-asymmetric dihydroxylation-N-oxidation, respectively, in the presence of Sharpless chiral ligand, (DHQD)2PHAL in a single pot using H2O2 as a terminal oxidant to provide N-methylmorpholine oxide (NMO) in situ by the oxidation of N-methylmorpholine (NMM). The heterogeneous bifunctional catalyst supported on LDH (LDH-OsW) displays superior activity to afford diols with higher yields over the other heterogeneous catalysts developed by the ion exchange on quaternary ammonium salts covalently bound to resin (resin-OsW) and silica (silica-OsW) or homogeneous catalysts in the achiral dihydroxylation reactions. The LDH-OsW and its homogeneous analogue are found to be very efficient in performing a simultaneous asymmetric dihydroxylation (AD)-N-oxidation of a wide and varied range of aromatic, cyclic, and mono, di-, and trisubstituted olefins to obtain chiral vicinal diols with higher yields and ee's using H2O2. Further, the use of OsO42--WO42-- WO42- catalysts as such or in the supported form offers a simplified procedure for catalyst recycling, which shows consistent activity for a number of cycles. In this process, OsVI is recycled to OsVIII by a coupled electron transfer-mediator (ETM) system based on NMO-WO42- using H2O2, leading to a mild and selective electron transfer. The one-pot biomimic synthesis of chiral diols is mediated by a recyclable trifunctional heterogeneous catalyst (LDH-PdOsW) consisting of active palladium, tungsten, and osmium species embedded in a single matrix. This protocol, which provides prochiral olefins and NMO in situ by Heck coupling and N-oxidation of NMM, respectively, required for the AD, unfolds a low cost process. We extended the present method to the one-pot synthesis of trisubstituted chiral vicinal diols with moderate to excellent ee's by AD of trisubstituted olefins that are obtained by in situ Heck arylation of disubstituted olefins. The heterogeneous trifunctional catalysts offers chiral diols with unprecedented ee's and excellent yields in the AD of prochiral cinnamates, which are obtained in situ from acrylates and halobenzenes for the first time. The new variants such as LDH support and Et3N·HX inherently composed in the heterogeneous multicomponent system and slow addition of H202 facilitates the hydrolysis of osmium monogylcolate ester to subdue the formation of bisglycolate ester to achieve higher ee's. Without resorting to recrystallization, the chiral diols of cinnamates thus synthesized with 99% ee's and devoid of osmium contamination are directly put to use in the synthesis of diltiazem and Taxol side chain with an overall improved yield to demonstrate the synthetic utility of the trifunctional heterogeneous catalyst. The high binding ability of the heterogeneous osmium catalyst enables the use of equimolar ratio of ligand to osmium to give excellent ee's in AD in contrast to the homogeneous osmium system in which the excess molar quantities of the expensive chiral ligand to osmium are invariably used. Further, the XRD, FT-IR, UV-vis DRS, and XPS studies indicate the retention of the coordination geometries of the specific divalent anions anchored to LDH matrix in their monomeric form during the ion exchange and after the reaction.
- Choudary, Boyapati M.,Chowdari, Naidu S.,Madhi, Sateesh,Kantam, Mannepalli L.
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p. 1736 - 1746
(2007/10/03)
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- A new practical method for the osmium-catalyzed dihydroxylation of olefins using bleach as the terminal oxidant
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A general procedure for the osmium-catalyzed dihydroxylation of various olefins using bleach as oxidant is reported for the first time. Aromatic and aliphatic olefins yield the corresponding cis-1,2-diols in the presence of dihydroquinine or dihydroquinidine derivatives (Sharpless ligands) with good to excellent chemo- and enantioselectivities under optimized pH conditions. In the presence of a small excess of bleach as reoxidant fast dihydroxylation takes place even at 0°C. Under optimum reaction conditions it is possible to dihydroxylate terminal aliphatic and aromatic olefins as well as internal olefins. The low price of the oxidant and the simple handling of bleach make this dihydroxylation variant attractive for further applications.
- Mehltretter, Gerald M.,Bhor, Santosh,Klawonn, Markus,D?bler, Christian,Sundermeier, Uta,Eckert, Markus,Militzer, Hans-Christian,Beller, Matthias
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p. 295 - 301
(2007/10/03)
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- Rhodium-catalyzed enantioselective diboration of simple alkenes
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Enantioselective catalytic reactions that operate directly on inexpensive unactivated alkenes are extraordinarily useful for the preparation of chiral organic building blocks and new materials. While a number of such processes have been developed, our ability to meet the intensifying demand for inexpensive stereochemically complex materials will require a significant expansion of practical catalytic asymmetric reaction methodology. In this regard, the rhodium-catalyzed enantioselective diboration reaction has been developed in order to address a number of extant problems in catalytic alkene transformation simultaneously. This process provides an enantiomerically enriched reactive dimetalated intermediate which can be converted to a variety of difunctional reaction products. Copyright
- Morgan, Jeremy B.,Miller, Steven P.,Morken, James P.
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p. 8702 - 8703
(2007/10/03)
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- The synthesis of the anti-malarial natural product polysphorin and analogues using polymer-supported reagents and scavengers.
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A general asymmetric route to both enantiomers of polysphorin has been developed. The route utilizes polymer-supported reagents, catalysts and scavengers to minimise the need for aqueous work-up and chromatography. This includes application of a method to scavenge 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) and a "catch-and-release" procedure to extract the resultant diol following Sharpless asymmetric dihydroxylation. A novel enzymatic selective protection and investigations of a new asymmetric dihydroxylation using microencapsulated osmium tetroxide were also investigated during the course of this study.
- Lee, Ai-Lan,Ley, Steven V
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p. 3957 - 3966
(2007/10/03)
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- MTO and OsO4: An efficient catalytic couple for mild H2O2-based asymmetric dihydroxylation of olefins
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A novel and robust system for osmium-catalyzed asymmetric dihydroxylation of olefins by aqueous H2O2 with methyltrioxorhenium (MTO) as electron transfer mediator (ETM) has been developed. The MTO is catalyzing the H2O2 oxidation of the chiral ligand to its mono-N-oxide, which in turn reoxidizes OsVI to OsVIII. Thus the (DHQD)2PHAL plays a dual role serving as the chiral inductor as well as the tertiary amine generating the N-oxide required for the recycling of osmium. The present catalytic system gives vicinal diols in good isolated yields and high enantiomeric excess (up to 99 % ee).
- Jonsson, Sandra Y.,Adolfsson, Hans,Baeckvall, Jan-E.
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p. 2783 - 2788
(2007/10/03)
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- Osmium tetroxide-(QN)2 PHAL in an ionic liquid: A highly efficient and recyclable catalyst system for asymmetric dihydroxylation of olefins
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In Os-catalysed asymmetric dihydroxylation using NMO as a co-oxidant, the combination of an ionic liquid and the new bis-cinchona alkaloid 2 generated in situ from (QN)2PHAL during reaction provided a simple and practical approach to the recycling of both catalytic components (osmium tetroxide and chiral ligand).
- Song, Choong Eui,Jung, Da-Un,Roh, Eun Joo,Lee, Sang-Gi,Chi, Dae Yoon
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p. 3038 - 3039
(2007/10/03)
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- Catalytic asymmetric dihydroxylation using phenoxyethoxymethyl-polystyrene (PEM)-based novel microencapsulated osmium tetroxide (PEM-MC OsO4)
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(Equation presented) A phenoxyethoxymethyl-polystyrene (PEM)-based novel polymer-supported osmium catalyst has been developed. The catalyst was readily prepared from PEM polymer based on a microencapsulation technique, and asymmetric dihydroxylation of olefins has been successfully performed using (DHQD)2PHAL as a chiral ligand and K3Fe(CN)6 as a cooxidant in H20/acetone. The catalyst was recovered quantitativery by simple filtration and reused without loss of activity several times.
- Kobayashi, Shu,Ishida, Tasuku,Akiyama, Ryo
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p. 2649 - 2651
(2007/10/03)
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