- Chemo- and Enantioselective Photoenzymatic Ketone Reductions Using a Promiscuous Flavin-dependent Nitroreductase
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Flavoenzymes are oxidoreductases that catalyze an extensive range of different types of reactions. An advanced and powerful approach to achieving transformations that are normally outside the realm of flavoenzymes is the synergistic combination of photocatalysis and biocatalysis. Here we report the identification of a promiscuous flavin-dependent nitroreductase, BaNTR1, that is able to promote enantioselective photobiocatalytic reductions of a broad range of structurally diverse ketones to yield the corresponding alcohols with high conversion (up to >99 %) and outstanding enantiopurity (up to >99 : 1 e.r). Noteworthy, BaNTR1 was able to promote the photoenzymatic reduction of various α,?-unsaturated ketones to give the corresponding optically pure alcohols without reducing the C=C or C≡C bond, illustrating its remarkably high chemoselectivity. Our results highlight the usefulness of photocatalysis for expanding the catalytic repertoire of nitroreductases to include highly enantio- and chemoselective reductions of non-native ketone substrates to produce optically pure alcohols. This includes difficult to prepare allyl alcohols that are not accessible via photoenzymatic conversions using ene-reductases.
- Bhat, Mohammad Faizan,Luján, Alejandro Prats,Poelarends, Gerrit J.,Saravanan, Thangavelu
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- Nickel-Catalyzed Enantioselective Hydroboration of Vinylarenes
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The enantioselective hydroboration of vinylarenes catalyzed by a chiral, nonracemic nickel catalyst is presented as a facile method for generating chiral benzylic boronate esters. Various vinylarenes react with bis(pinacolato)diboron (B2pin2) in the presence of MeOH as a hydride source to form chiral boronate esters in up to 92% yield with up to 94% ee. The use of anhydrous Me4NF to activate B2pin2 is crucial for ensuring fast transmetalation to achieve high enantioselectivities.
- Tran, Hai N.,Stanley, Levi M.
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supporting information
p. 395 - 399
(2021/12/27)
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- Regioselective asymmetric bioreduction of trans-4-phenylbut-3-en-2-one by whole-cell of Weissella cibaria N9 biocatalyst
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There is a considerable interest in the asymmetric production of chiral allylic alcohols, the main building blocks of many functional molecules. The asymmetric reduction of α,β-unsaturated ketones is difficult with traditional chemical protocols in a regi
- Kalay, Erbay,?ahin, Engin
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p. 535 - 542
(2021/07/14)
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- Cobalt-Catalyzed Enantiospecific Dynamic Kinetic Cross-Electrophile Vinylation of Allylic Alcohols with Vinyl Triflates
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Asymmetric cross-electrophile coupling has emerged as a promising tool for producing chiral molecules; however, the potential of this chemistry with metals other than nickel remains unknown. Herein, we report a cobalt-catalyzed enantiospecific vinylation
- Han, Guan-Yu,Kang, Shaolin,Liu, Xue-Yuan,Ma, Wei-Yuan,Pang, Xiaobo,Shu, Xing-Zhong
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supporting information
p. 15930 - 15935
(2021/10/20)
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- Alcohol Dehydrogenases and N-Heterocyclic Carbene Gold(I) Catalysts: Design of a Chemoenzymatic Cascade towards Optically Active β,β-Disubstituted Allylic Alcohols
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The combination of gold(I) and enzyme catalysis is used in a two-step approach, including Meyer–Schuster rearrangement of a series of readily available propargylic alcohols followed by stereoselective bioreduction of the corresponding allylic ketone intermediates, to provide optically pure β,β-disubstituted allylic alcohols. This cascade involves a gold N-heterocyclic carbene and an enzyme, demonstrating the compatibility of both catalyst types in aqueous medium under mild reaction conditions. The combination of [1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene][bis(trifluoromethanesulfonyl)-imide]gold(I) (IPrAuNTf2) and a selective alcohol dehydrogenase (ADH-A from Rhodococcus ruber, KRED-P1-A12 or KRED-P3-G09) led to the synthesis of a series of optically active (E)-4-arylpent-3-en-2-ols in good yields (65–86 %). The approach was also extended to various 2-hetarylpent-3-yn-2-ol, hexynol, and butynol derivatives. The use of alcohol dehydrogenases of opposite selectivity led to the production of both allyl alcohol enantiomers (93->99 % ee) for a broad panel of substrates.
- González-Granda, Sergio,Lavandera, Iván,Gotor-Fernández, Vicente
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supporting information
p. 13945 - 13951
(2021/04/22)
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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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- Manganese catalyzed enantio- and regioselective hydrogenation of α,β-unsaturated ketones using an imidazole-based chiral PNN tridentate ligand
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The enantioselective 1,2-reduction of α,β-unsaturated ketones has been achieved using a chiral pincer Mn catalyst. A series of PNN tridentate ligands containing benzimidazole groups were designed with ferrocene as the backbone, which coordinated with Mn t
- Wang, Ze,Zhao, Xianghua,Huang, An,Yang, Zehui,Cheng, Yuqi,Chen, Jiachen,Ling, Fei,Zhong, Weihui
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supporting information
(2021/09/22)
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- Mn(i) phosphine-amino-phosphinites: a highly modular class of pincer complexes for enantioselective transfer hydrogenation of aryl-alkyl ketones
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A series of Mn(i) catalysts with readily accessible and more π-accepting phosphine-amino-phosphinite (P′(O)N(H)P) pincer ligands have been explored for the asymmetric transfer hydrogenation of aryl-alkyl ketones which led to good to high enantioselectivities (up to 98%) compared to other reported Mn-based catalysts for such reactions. The easy tunability of the chiral backbone and the phosphine moieties makes P′(O)N(H)P an alternative ligand framework to the well-known PNP-type pincers.
- Jayaprakash, Harikrishnan
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supporting information
p. 14115 - 14119
(2021/10/25)
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- Fine-Tuning the Micro-Environment to Optimize the Catalytic Activity of Enzymes Immobilized in Multivariate Metal-Organic Frameworks
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The artificial engineering of an enzyme’s structural conformation to enhance its activity is highly desired and challenging. Anisotropic reticular chemistry, best illustrated in the case of multivariate metal-organic frameworks (MTV-MOFs), provides a platform to modify a MOF’s pore and inner-surface with functionality variations on frameworks to optimize the interior environment and to enhance the specifically targeted property. In this study, we altered the functionality and ratio of linkers in zeolitic imidazolate frameworks (ZIFs), a subclass of MOFs, with the MTV approach to demonstrate a strategy that allows us to optimize the activity of the encapsulated enzyme by continuously tuning the framework-enzyme interaction through the hydrophilicity change in the pores’ microenvironment. To systematically study this interaction, we developed the component-adjustment-ternary plot (CAT) method to approach the optimal activity of the encapsulated enzyme BCL and revealed a nonlinear correlation, first incremental and then decremental, between the BCL activity and the hydrophilic linker’ ratios in MTV-ZIF-8. These findings indicated there is a spatial arrangement of functional groups along the three-dimensional space across the ZIF-8 crystal with a unique sequence that could change the enzyme structure between closed-lid and open-lid conformations. These conformation changes were confirmed by FTIR spectra and fluorescence studies. The optimized BCL@ZIF-8 is not only thermally and chemically more stable than free BCL in solution, but also doubles the catalytic reactivity in the kinetic resolution reaction with 99%eeof the products.
- Li, Yi-Ming,Yuan, Jian,Ren, Hao,Ji, Chun-Yan,Tao, Yu,Wu, Yahui,Chou, Lien-Yang,Zhang, Yue-Biao,Cheng, Lin
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supporting information
p. 15378 - 15390
(2021/09/18)
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- Mechanochemical, Water-Assisted Asymmetric Transfer Hydrogenation of Ketones Using Ruthenium Catalyst
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Asymmetric catalytic reactions are among the most convenient and environmentally benign methods to obtain optically pure compounds. The aim of this study was to develop a green system for the asymmetric transfer hydrogenation of ketones, applying chiral Ru catalyst in aqueous media and mechanochemical energy transmission. Using a ball mill we have optimized the milling parameters in the transfer hydrogenation of acetophenone followed by reduction of various substituted derivatives. The scope of the method was extended to carbo- and heterocyclic ketones. The scale-up of the developed system was successful, the optically enriched alcohols could be obtained in high yields. The developed mechanochemical system provides TOFs up to 168 h?1. Our present study is the first in which mechanochemically activated enantioselective transfer hydrogenations were carried out, thus, may be a useful guide for the practical synthesis of optically pure chiral secondary alcohols.
- Kolcsár, Vanessza Judit,Sz?ll?si, Gy?rgy
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- An Amine-Assisted Ionic Monohydride Mechanism Enables Selective Alkyne cis-Semihydrogenation with Ethanol: From Elementary Steps to Catalysis
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The selective synthesis of Z-alkenes in alkyne semihydrogenation relies on the reactivity difference of the catalysts toward the starting materials and the products. Here we report Z-selective semihydrogenation of alkynes with ethanol via a coordination-induced ionic monohydride mechanism. The EtOH-coordination-driven Cl- dissociation in a pincer Ir(III) hydridochloride complex (NCP)IrHCl (1) forms a cationic monohydride, [(NCP)IrH(EtOH)]+Cl-, that reacts selectively with alkynes over the corresponding Z-alkenes, thereby overcoming competing thermodynamically dominant alkene Z-E isomerization and overreduction. The challenge for establishing a catalytic cycle, however, lies in the alcoholysis step; the reaction of the alkyne insertion product (NCP)IrCl(vinyl) with EtOH does occur, but very slowly. Surprisingly, the alcoholysis does not proceed via direct protonolysis of the Ir-C(vinyl) bond. Instead, mechanistic data are consistent with an anion-involved alcoholysis pathway involving ionization of (NCP)IrCl(vinyl) via EtOH-for-Cl substitution and reversible protonation of Cl- ion with an Ir(III)-bound EtOH, followed by β-H elimination of the ethoxy ligand and C(vinyl)-H reductive elimination. The use of an amine is key to the monohydride mechanism by promoting the alcoholysis. The 1-amine-EtOH catalytic system exhibits an unprecedented level of substrate scope, generality, and compatibility, as demonstrated by Z-selective reduction of all alkyne classes, including challenging enynes and complex polyfunctionalized molecules. Comparison with a cationic monohydride complex bearing a noncoordinating BArF- ion elucidates the beneficial role of the Cl- ion in controlling the stereoselectivity, and comparison between 1-amine-EtOH and 1-NaOtBu-EtOH underscores the fact that this base variable, albeit in catalytic amounts, leads to different mechanisms and consequently different stereoselectivity.
- Huang, Zhidao,Wang, Yulei,Leng, Xuebing,Huang, Zheng
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p. 4824 - 4836
(2021/04/07)
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- One-pot two-step chemoenzymatic deracemization of allylic alcohols using laccases and alcohol dehydrogenases
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A series of enantioenriched (hetero)aromatic secondary allylic alcohols has been synthesized through deracemization of the corresponding racemic mixtures combining a non-selective chemoenzymatic oxidation (laccase from Trametes versicolor and oxy-radical TEMPO) and a stereoselective biocatalyzed reduction (lyophilized cells of E. coli overexpressing an alcohol dehydrogenase, ADH). Both steps were performed in aqueous medium under very mild reaction conditions. After optimization, a sequential one-pot two-step protocol was set up, obtaining the corresponding chiral alcohols in moderate to high conversions (48–95%) and enantiomeric excess (65->99% ee). Depending on the ADH stereopreference, both antipodes from these valuable chiral synthons could be prepared, even at preparative scale (119?178 mg), in a straightforward manner.
- Albarrán-Velo, Jesús,Gotor-Fernández, Vicente,Lavandera, Iván
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- Preparation method of (R,E)-4-phenylbutyl-3-ene-2-ol derivative
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The invention discloses a preparation method of a (R,E)-4-phenylbutyl-3-ene-2-ol derivative. Specifically, asymmetric hydrogenation is carried out on the (E)-4-phenyl-3-ene-2-one derivative by adopting a catalyst consisting of a PNN ligand of a chiral fer
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Paragraph 0044-0067
(2020/11/22)
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- Highly activity asymmetric hydrogenation of enones catalyzed by iridium complexes with chiral diamines and achiral phosphines
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A selective asymmetric hydrogenation of enones has been well established by using an iridium complex composed of cheap phosphine ligands and cinchona alkaloids derivatives as catalyst. A wide range of allylic alcohol products could be obtained in high chemoselectivities (up to 99.6%), enantioselectivities (70.1% ee) and high activities (up to 3.64 × 104(1/h) TOF). This catalytic system opens a new way of selective asymmetric hydrogenation and the method can be of practical value.
- Chen, Hua,Gao, Xiuli,Jiang, Jian,Li, Chun,Li, Li,Lu, Xunhua,Wang, Mengna,Zhang, Lin,Zhang, Ling
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- Chelate ring size effects of Ir(P,N,N) complexes: Chemoselectivity switch in the asymmetric hydrogenation of α,β-unsaturated ketones
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A novel, highly modular approach has been developed for the synthesis of new chiral P,N,N ligands with the general formula Ph2P(CH3)CH(CH2)mCH(CH3)NHCH2CH2(CH2)nN(CH3)2 and Ph2P(CH3)CHCH2CH(CH3)NHCH2(CH2)n-2-Py (m, n = 0, 1). The systematic variation of their P–N and N–N backbone led to the conclusion that the activity, chemo- and enantioselectivity in the hydrogenation of α,β-unsaturated ketones are highly dependent on the combination of the two bridge lengths. It has been found that a minor change in the ligand's structure, i. e. varying the value of m from 1 to 0, can switch the chemoselectivity of the reaction, from 80percent C[dbnd]O to 97percent C[dbnd]C selectivity.
- Bényei, Attila C.,Bakos, József,Császár, Zsófia,Farkas, Gergely,Szabó, Eszter Z.
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- Total Synthesis of Meayamycin B
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Meayamycin B is currently the most potent modulator of the splicing factor 3b subunit 1 and used by dozens of research groups. However, current supply for this natural product analogue is limited because of the lengthy synthetic scheme. Here, we report a more concise, more cost-effective, and greener synthesis of this compound by developing and employing a novel asymmetric reduction of a prochiral enone to afford an allylic alcohol with high enantioselectivity. In addition to this reaction, this synthesis highlights a scalable Mukaiyama aldol reaction, Nicolaou-type epoxide opening reaction, stereoselective Corey-Chaykovsky-type reaction, and a modified Horner-Wadsworth-Emmons Z-selective olefination. We also discuss a Z-E isomerization during the α,β-unsaturated amide formation. The new synthesis of meayamycin B consists of 11 steps in the longest linear sequence and 24 total steps.
- Basu, Upamanyu,Bressin, Robert K.,Koide, Kazunori,Osman, Sami,Pohorilets, Ivanna
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supporting information
p. 4637 - 4647
(2020/05/01)
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- Production of enantiomerically enriched chiral carbinols using whole-cell biocatalyst
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Biocatalytic asymmetric reduction of ketone is an efficient method for the production of chiral carbinols. The study indicates selective bioreduction of different ketones (1–8) to their respective (R)-alcohols (1a–8a) in low to high selectivity (0- >99%) with good yields (11–96%). In this work, whole-cell of Lactobacillus kefiri P2 catalysed enantioselective reduction of various prochiral ketones was investigated. (R)-4-Phenyl-2-butanol 2a, which is used as a precursor to antihypertensive agents and spasmolytics (anti-epileptic agents), was obtained using L kefiri P2 in 99% conversion and 91% enantiomeric excess (ee). Moreover, bioreduction of 2-methyl-1-phenylpropan-1-one substrate 8, containing a branched alkyl chain and difficult to asymmetric reduction with chemical catalysts as an enantioselective, to (R)-2-methyl-1-phenylpropan-1-ol (8a) in enantiomerically pure form was carried out in excellent yield (96%). The gram-scale production was carried out, and 9.70 g of (R)-2-methyl-1-phenylpropan-1-ol (8a) in enantiomerically pure form was obtained in 96% yield. Also especially, the yield and gram scale of (R)-2-methyl-1-phenylpropan-1-ol (8a) synthesised through catalytic asymmetric reduction using the biocatalyst was the highest report so far. The efficiency of L kefiri P2 for the conversion of the substrates and ee of products were markedly influenced by the steric factors of the substrates. This is a cheap, clean and eco-friendly process for production of chiral carbinols compared to chemical processes.
- ?ahin, Engin,Bayda?, Yasemin,Kalay, Erbay
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- Continuous-Flow Dynamic Kinetic Resolution of Racemic Alcohols by Lipase–Oxovanadium Cocatalysis
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A continuous-flow dynamic kinetic resolution of racemic secondary alcohols was carried out using a single column reactor packed with a mixture of immobilized lipase and an immobilized oxovanadium species, VMPS4. As a result, optically pure esters were produced in 88–92 % yields. Problems encountered in this study were overcome by using fillers that efficiently maintained the initial distribution of the catalysts in the reactor and by using a packing method in which the mixing ratio of the two catalysts was varied in a stepwise fashion. The flow process led to an increased turnover number of each catalyst compared to those of batch reactions.
- Adebar, Niklas,Akai, Shuji,Gr?ger, Harald,Higashio, Koichi,Kühn, Franziska,Katsuragi, Satoko,Kundu, Dhiman,Plass, Carmen
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supporting information
p. 1961 - 1967
(2020/04/09)
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- Protecting-Group-Free Total Synthesis of Chatenaytrienin-2
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An efficient seven-step, protecting-group-free first total synthesis of chatenaytrienin-2 based on ring-closing metathesis and C(sp)-C(sp3) Sonogashira coupling with a 36.5% overall yield has been described. The ready availability of starting m
- Kunkalkar, Rupesh A.,Fernandes, Rodney A.
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p. 12216 - 12220
(2019/10/11)
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- Enantioselective Hydrogenation of Ketones using Different Metal Complexes with a Chiral PNP Pincer Ligand
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The synthesis of different metal pincer complexes coordinating to the chiral PNP ligand bis(2-((2R,5R)-2,5-dimethyl-phospholanoethyl))amine is described in detail. The characterized complexes with Mn, Fe, Re and Ru as metal centers showed good activities regarding the reduction of several prochiral ketones. Comparing these catalysts, the non-noble metal complexes produced best selectivities not only for aromatic substrates, but also for different kinds of aliphatic ones leading to enantioselectivities up to 99% ee. Theoretical investigations elucidated the mechanism and rationalized the selectivity. (Figure presented.).
- Garbe, Marcel,Wei, Zhihong,Tannert, Bianca,Spannenberg, Anke,Jiao, Haijun,Bachmann, Stephan,Scalone, Michelangelo,Junge, Kathrin,Beller, Matthias
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supporting information
p. 1913 - 1920
(2019/03/13)
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- Biocatalytic Enantioselective Oxidation of Sec-Allylic Alcohols with Flavin-Dependent Oxidases
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The oxidation of allylic alcohols is challenging to perform in a chemo- as well as stereo-selective fashion at the expense of molecular oxygen using conventional chemical protocols. Here, we report the identification of a library of flavin-dependent oxidases including variants of the berberine bridge enzyme (BBE) analogue from Arabidopsis thaliana (AtBBE15) and the 5-(hydroxymethyl)furfural oxidase (HMFO) and its variants (V465T, V465S, V465T/W466H and V367R/W466F) for the enantioselective oxidation of sec-allylic alcohols. While primary and benzylic alcohols as well as certain sugars are well known to be transformed by flavin-dependent oxidases, sec-allylic alcohols have not been studied yet except in a single report. The model substrates investigated were oxidized enantioselectively in a kinetic resolution with an E-value of up to >200. For instance HMFO V465S/T oxidized the (S)-enantiomer of (E)-oct-3-en-2-ol (1 a) and (E)-4-phenylbut-3-en-2-ol with E>200 giving the remaining (R)-alcohol with ee>99% at 50% conversion. The enantioselectivity could be decreased if required by medium engineering by the addition of cosolvents (e. g. dimethyl sulfoxide).
- Gandomkar, Somayyeh,Jost, Etta,Loidolt, Doris,Swoboda, Alexander,Pickl, Mathias,Elaily, Wael,Daniel, Bastian,Fraaije, Marco W.,Macheroux, Peter,Kroutil, Wolfgang
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p. 5264 - 5271
(2019/11/13)
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- Asymmetric Magnesium-Catalyzed Hydroboration by Metal-Ligand Cooperative Catalysis
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Asymmetric catalysis with readily available, cheap, and non-toxic alkaline earth metal catalysts represents a sustainable alternative to conventional synthesis methodologies. In this context, we describe the development of a first MgII-catalyzed enantioselective hydroboration providing the products with excellent yields and enantioselectivities. NMR spectroscopy studies and DFT calculations provide insights into the reaction mechanism and the origin of the enantioselectivity which can be explained by a metal-ligand cooperative catalysis pathway involving a non-innocent ligand.
- Falconnet, Alban,Magre, Marc,Maity, Bholanath,Cavallo, Luigi,Rueping, Magnus
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supporting information
p. 17567 - 17571
(2019/11/13)
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- Stereoselective Modification of N-(α-Hydroxyacyl)-glycinesters via Palladium-Catalyzed Allylic Alkylation
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N-(α-Hydroxyacyl)-glycinesters can be used as excellent nucleophiles in Pd-catalyzed allylic alkylation. The method allows for the stereoselective introduction of a wide range of side chains, including highly functionalized ones. Both diastereomers can be accessed through variation of the reaction conditions. Furthermore, the use of stannylated carbonates introduces vinylstannane motifs, which are eligible for subsequent C-C coupling reactions.
- Horn, Alexander,Kazmaier, Uli
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supporting information
p. 4595 - 4599
(2019/06/27)
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- Manganese complex and preparation method and application thereof
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The invention discloses a manganese complex taking (RC,SP)-N-5,6,7,8-tetrahydroquinoline-1-(2-diphenylphosphino)ferrocene ethyl amine as a ligand, a preparation method and application of the manganesecomplex in catalyst ketone compound asymmetric hydrogen transfer reduction preparing chiral alcohol. The manganese complex is a cheap metal chiral catalyst, the cost is low, the thermal stability isgood, and the preparation method of the manganese complex has the advantages of mild condition, short period, simple operation condition and the like. The catalyst is used for reducing the chiral alcohol for ketone hydrogen transfer, has higher catalytic activity, and a method for preparing the chiral alcohol is simple, less in environment pollution, and high in yield.
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Paragraph 0063-0066; 0069-0077
(2020/01/03)
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- A 1,3,2-Diazaphospholene-Catalyzed Reductive Claisen Rearrangement
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1,3,2-Diazaphospholenes (DAPs) are an emerging class of organic hydrides. In this work, we exploited them as efficient catalysts for very mild reductive Claisen rearrangements. The method is tolerant towards a wide variety of functional groups and operates at ambient temperature. Besides being enantiospecific for substrates with existing stereogenic centers, the diastereoselectivity can be switched by varying solvents and DAP catalysts. The reaction kinetics show direct rearrangements of O-bound phospholene enolates and provide a proof-of-principle for catalytic enantioselective reactions.
- Reed, John H.,Donets, Pavel A.,Miaskiewicz, Solène,Cramer, Nicolai
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p. 8893 - 8897
(2019/05/28)
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- Asymmetric Transfer Hydrogenation with a Bifunctional Iron(II) Hydride: Experiment Meets Computation
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Hydride cis-β-[FeH(CNCEt3)(1)]BF4 (5) (1 is a chiral N2P2 macrocycle) is the catalytically active species in the asymmetric transfer hydrogenation of ketones formed upon reaction of [Fe(CNCEt3)2(1)](BF4)2 (3) with base. Stoichiometric reactions show that hydride 5 is formed by H-elimination from the 2-propoxo complex [Fe(OiPr)(CNCEt3)(1)]BF4 (8a) and inserts the C=O bond of acetophenone to give the diastereoisomeric alcoholato complexes [Fe(OCH(Me)Ph)(CNCEt3)(1)]BF4 (10R and 10S). Complexes 5, 8a, and 10 were characterized by NMR spectroscopy, and their structures were calculated by DFT. The DFT study supports a bifunctional mechanism with the alkoxo complexes 8a and 10 as resting species. The stereochemical model reproduces the high enantioselectivity with acetophenone, which results from the combination of the rigid macrocyclic scaffold with the bulky, yet conformationally flexible isonitrile.
- De Luca, Lorena,Passera, Alessandro,Mezzetti, Antonio
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supporting information
(2019/02/14)
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- Enantioselective Reduction of α,β-Unsaturated Ketones and Aryl Ketones by Perakine Reductase
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This report describes the enantioselective reduction of structurally diverse α,β-unsaturated ketones and aryl ketones by perakine reductase (PR) from Rauvolfia. This enzymatic reduction produces α-chiral allylic and aryl alcohols with excellent enantioselectivity and most of the products in satisfactory yields. Furthermore, the work demonstrates 1 mmol scale reactions for product delivery without any detrimental effect on yield and enantioselectivity. The catalytic mechanism, determined by 3D-structure-based modeling of PR and ligand complexes, is also described.
- Cai, Sheng,Shao, Nana,Chen, Yuanyuan,Li, Anbang,Pan, Jie,Zhu, Huajian,Zou, Hongbin,Zeng, Su,Sun, Lianli,Zhao, Jinhao
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supporting information
p. 4411 - 4414
(2019/05/22)
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- Enhanced activity and modified substrate-favoritism of Burkholderia cepacia lipase by the treatment with a pyridinium alkyl-PEG sulfate ionic liquid
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Three types of pyridinium salts, i.e., 1-ethylpyridin-1-ium cetyl-PEG10 sulfate (PYET), 1-butylpyridin-1-ium cetyl-PEG10 sulfate (PYBU), and 1-(3-methoxypropyl)pyridin-1-ium cetyl-PEG10 sulfate (PYMP), have been prepared and evaluated for their activation property of Burkholderia cepacia lipase by comparison to the control IL-coated enzymes, 1-butyl-2,3-dimethylimidazolium cetyl-PEG10 sulfate-coated lipase PS (IL1-PS). Among the tested pyridinium salt-coated lipases, the PYET-coated lipase PS (PYET-PS) exhibited the best results; the transesterification of 1-(pyridin-2-yl)ethanol, 1-(pyridin-3-yl)ethanol, 1-(pyridin-4-yl)ethanol, or 4-phenylbut-3-en-2-ol proceeded faster than those of the IL1-PS-catalyzed reaction while maintaining an excellent enantioselectivity (E > 200). This improved efficiency was found to be dependent on the increased Kcat value.
- Kadotani, Shiho,Nokami, Toshiki,Itoh, Toshiyuki
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p. 441 - 447
(2019/01/04)
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- Expanding the Substrate Specificity of Thermoanaerobacter pseudoethanolicus Secondary Alcohol Dehydrogenase by a Dual Site Mutation
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Here, we report the asymmetric reduction of selected phenyl-ring-containing ketones by various single- and dual-site mutants of Thermoanaerobacter pseudoethanolicus secondary alcohol dehydrogenase (TeSADH). The further expansion of the size of the substrate binding pocket in the mutant W110A/I86A not only allowed the accommodation of substrates of the single mutants W110A and I86A within the expanded active site but also expanded the substrate range of the enzyme to ketones bearing two sterically demanding groups (bulky–bulky ketones), which are not substrates for the TeSADH single mutants. We also report the regio- and enantioselective reduction of diketones with W110A/I86A TeSADH and single TeSADH mutants. The double mutant exhibited dual stereopreference to generate the Prelog products most of the time and the anti-Prelog products in a few cases.
- Musa, Musa M.,Bsharat, Odey,Karume, Ibrahim,Vieille, Claire,Takahashi, Masateru,Hamdan, Samir M.
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p. 798 - 805
(2018/02/21)
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- The synthesis of non-racemic β-alkyl-β-aryl-disubstituted allyl alcohols and their transformation into allylamines and amino acids bearing a quaternary stereocenter
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A synthesis of non-racemic β-alkyl-β-aryl allyl alcohols and their transformation into allylamines bearing a quaternary stereogenic center is reported. The allyl alcohols were prepared either by Cu-catalyzed enantioselective reduction of enones or by sequ
- Narczyk, Aleksandra,Pieczykolan, Micha?,Stecko, Sebastian
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p. 3921 - 3946
(2018/06/08)
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- Acylative Kinetic Resolution of Alcohols Using a Recyclable Polymer-Supported Isothiourea Catalyst in Batch and Flow
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A polystyrene-supported isothiourea catalyst, based on the homogeneous catalyst HyperBTM, has been prepared and used for the acylative kinetic resolution of secondary alcohols. A wide range of alcohols, including benzylic, allylic, and propargylic alcohols, cycloalkanol derivatives, and a 1,2-diol, has been resolved using either propionic or isobutyric anhydride with good to excellent selectivity factors obtained (28 examples, s values up to 600). The catalyst can be recovered and reused by a simple filtration and washing sequence, with no special precautions needed. The recyclability of the catalyst was demonstrated (15 cycles) with no significant loss in either activity or selectivity. The recyclable catalyst was also used for the sequential resolution of 10 different alcohols using different anhydrides with no cross-contamination between cycles. Finally, successful application in a continuous flow process demonstrated the first example of an immobilized Lewis base catalyst used for the kinetic resolution of alcohols in flow.
- Neyyappadath, Rifahath Mon,Chisholm, Ross,Greenhalgh, Mark D.,Rodríguez-Escrich, Carles,Pericàs, Miquel A.,H?hner, Georg,Smith, Andrew D.
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p. 1067 - 1075
(2018/02/14)
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- CHIRAL METAL COMPLEX COMPOUNDS
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The invention comprises novel chiral metal complex compounds of the formula (I) wherein M, PR2, R3 and R4 are outlined in the description, its stereoisomers, in the form as a neutral complex or a complex cation with a suitable counter ion. The chiral metal complex compounds can be used in asymmetric reactions, particularly in asymmetric reductions of ketones, imines or oximes.
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-
Page/Page column 24; 28
(2018/11/10)
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- Iridium and Rhodium Complexes Containing Enantiopure Primary Amine-Tethered N-Heterocyclic Carbenes: Synthesis, Characterization, Reactivity, and Catalytic Asymmetric Hydrogenation of Ketones
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The imidazolium salt [(S,S)-tBuNC3H3NCHPhCHPhNH2]PF6, (S,S)-11·HPF6 is a precursor to the enantiopure "Kaibene" ligand, tBu-Kaibene, (S,S)-11 featuring a tert-butyl group on the N-heterocyclic carbene (NHC) ring-nitrogen atoms. It has been prepared in high yield and purity by refluxing a chiral cyclic sulfamidate with 1-tert-butylimidazole. Similarly (S,S)-12·HPF6 with a mesityl group at the imidazolium ring-nitrogen atom has been prepared in the same fashion and serves as a source of Mes-Kaibene, (S,S)-12. These bidentate Kaibene ligands feature an NHC and a primary amine separated by a chiral linker. Salts (S,S)-11·HPF6 or (S,S)-12·HPF6 react with base and AgI or CuI to give a total of four M(Kaibene)2I compounds (M = Ag or Cu). At 22 °C, the amine-functionalized imidazolium cations undergo oxidative addition to iridium(I) in [IrCl(cod)]2 (cod = 1,5-cyclooctadiene) to generate iridium(III) hydride R-Kaibene compounds [IrHCl(cod)((S,S)-11)](PF6) (17) and [IrHCl(cod)((S,S)-12)](PF6) (18), respectively, each as a mixture of six configurational isomers. In contrast, the salt (S,S)-11·HPF6 reacts with [Ir(OtBu)(cod)]2 to produce a bimetallic iridium compound with (S,S)-11 as the bridging ligand. This compound contains interesting NH···Cl and NH···Ir noncovalent intramolecular interactions. Salt (S,S)-12·HPF6 reacts with silver oxide to yield [Ag2((S,S)-12)2](PF6)2 (20). Reagent 20 serves as an efficient transmetalation reagent to deliver to each rhodium in [RhCl(cod)]2 1 equiv of (S,S)-12 as a bidentate ligand to give [Rh(cod)((S,S)-12)](PF6). In the reaction between [IrCl(cod)]2 and 20, (S,S)-12 ends up coordinated in an iridium(III) hydride complex (22) as a tridentate ligand via the NHC, NH2, and a cyclometalated phenyl group. The two iridium hydride compounds, 18 and 22, are catalysts for the hydrogenation of a range of ketones (turnover number up to 499, turnover frequency up to 249 h-1, with er (enantiomeric ratio) up to 35:65 R:S).
- Wan, Kai Y.,Roelfes, Florian,Lough, Alan J.,Hahn, F. Ekkehardt,Morris, Robert H.
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supporting information
p. 491 - 504
(2018/02/17)
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- Enantioselective NiH/Pmrox-Catalyzed 1,2-Reduction of α,β-Unsaturated Ketones
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The enantioselective 1,2-reduction of α,β-unsaturated ketones was achieved using a NiH catalyst in the presence of pinacolborane. This mild process represents a general method to access a wide variety of structurally diverse α-chiral allylic alcohols in excellent yields and enantioselectivity, as well as very high levels of ambidoselectivity for 1,2- over 1,4-reduction. Furthermore, for reactions on a 10 mmol scale, catalyst loadings as low as 0.5 mol % could be employed to deliver product without any detrimental effect on the yield, enantio-, or ambidoselectivity.
- Chen, Fenglin,Zhang, Yao,Yu, Lei,Zhu, Shaolin
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supporting information
p. 2022 - 2025
(2017/02/15)
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- Base-Free Asymmetric Transfer Hydrogenation of 1,2-Di- and Monoketones Catalyzed by a (NH)2P2-Macrocyclic Iron(II) Hydride
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The hydride isonitrile complex [FeH(CNCEt3)(1 a)]BF4 (2) containing a chiral P2(NH)2 macrocycle (1 a), in the presence of 2-propanol as hydrogen donor, catalyzes the base-free asymmetric transfer hydrogenation (ATH) of prostereogenic ketones to alcohols and the hemihydrogenation of benzils to benzoins, which contain a base-labile stereocenter. Benzoins are formed in up to 83 % isolated yield with enantioselectivity reaching 95 % ee. Ketones give the same enantioselectivity observed with the parent catalytic system [Fe(CNCEt3)2(1 a)] (3 a) that operates with added NaOtBu.
- De Luca, Lorena,Mezzetti, Antonio
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supporting information
p. 11949 - 11953
(2017/09/20)
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- Mechanism-Based Enantiodivergence in Manganese Reduction Catalysis: A Chiral Pincer Complex for the Highly Enantioselective Hydroboration of Ketones
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A manganese alkyl complex containing a chiral bis(oxazolinyl-methylidene)isoindoline pincer ligand is a precatalyst for a catalytic system of unprecedented activity and selectivity in the enantioselective hydroboration of ketones, thus producing preparatively useful chiral alcohols in excellent yields with up to greater than 99 % ee. It is applicable for both aryl alkyl and dialkyl ketone reduction under mild reaction conditions (TOF >450 h?1 at ?40 °C). The earth-abundant base-metal catalyst operates at very low catalyst loadings (as low as 0.1 mol %) and with a high level of functional-group tolerance. There is evidence for the existence of two distinct mechanistic pathways for manganese-catalyzed hydride transfer and their role for enantiocontrol in the selectivity-determining step is presented.
- Vasilenko, Vladislav,Blasius, Clemens K.,Wadepohl, Hubert,Gade, Lutz H.
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supporting information
p. 8393 - 8397
(2017/07/11)
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- Catalytic asymmetric Meerwein-Ponndorf-Verley reduction of glyoxylates induced by a chiral N,N′-dioxide/Y(OTf)3 complex
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An asymmetric Meerwein-Ponndorf-Verley (MPV) reduction of glyoxylates was for the first time accomplished via an N,N′-dioxide/Y(OTf)3 complex with aluminium alkoxide and molecular sieves (MSs) as crucial additives. A variety of optically active α-hydroxyesters were obtained with excellent results. A possible reaction mechanism was proposed based on the experiments.
- Wu, Wangbin,Zou, Sijia,Lin, Lili,Ji, Jie,Zhang, Yuheng,Ma, Baiwei,Liu, Xiaohua,Feng, Xiaoming
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supporting information
p. 3232 - 3235
(2017/03/20)
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- Asymmetric Transfer Hydrogenation of Ketones Using New Iron(II) (P-NH-N-P′) Catalysts: Changing the Steric and Electronic Properties at Phosphorus P′
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The asymmetric transfer hydrogenation (ATH) of ketones is an efficient method for producing enantio-enriched alcohols which are used as intermediates in a variety of industrial processes. Here we report the synthesis of new iron ATH precatalysts (S,S)-[FeBr(CO)(Ph2PCH2CH2NHCHPhCHPhNC=CHCH2PR′2)][BPh4] (R′=Et, and ortho-tolyl (o-Tol)) where one of the phosphine groups is modified with small alkyl and large aryl substituents to probe the effect of this change on the activity and selectivity of the catalytic system. A simple reversible equilibrium kinetic model is used to obtain the initial TOF and the inherent enantioselectivity S=kR/kS of these catalysts along with those for the previously reported catalysts with R′=Ph and Cy for the ATH of acetophenone. With an increase in the size of the PR′2 group, the TOF goes through a maximum at PPh2 while the S value goes through a maximum of 510 at R′=Cy. The complex with R′=o-Tol starts with a high S value of 200 but is rapidly changed to a second catalyst with an S value of 28. For the reduction of acetophenone to (R)-1-phenylethanol, turnover numbers of up to 5200 and ee up to 98 % were achieved. The chemotherapeutic pharmaceutical precursor (R)-(3′,5′-bis(trifluoromethyl))-1-phenylethanol is synthesized in up to 95 % ee. Several other alcohols can be prepared in greater than 90 % ee by choosing the precatalyst with the correctly matched steric properties. A hydride complex derived from the catalyst with R′=Cy is characterized by NMR spectroscopy. It is proposed that low concentration trans-hydride carbonyl complexes with the FeH parallel to the NH of the ligand are the active catalysts in all of these systems.
- Smith, Samantha A. M.,Prokopchuk, Demyan E.,Morris, Robert H.
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p. 1204 - 1215
(2017/09/06)
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- Remarkably improved stability and enhanced activity of a: Burkholderia cepacia lipase by coating with a triazolium alkyl-PEG sulfate ionic liquid
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Three types of triazolium cetyl-PEG10 sulfate ionic liquid were synthesized and their activation of Burkholderia cepacia lipase was investigated; both the reaction rate and enantioselectivity depended on the cationic part of the coating ILs and 1-butyl-3-methyl-1,2,3-triazolium cetyl-PEG10 sulfate (Tz1)-coated lipase PS, which is especially suitable for the transesterification of 1-(pyridin-2-yl)ethanol, 1-(pyridin-3-yl)ethanol, and 1-(pyridin-4-yl)ethanol, among 12 types of tested secondary alcohol. The most important result was obtained when these enzymes were stored in an IL ([N221MEM][Tf2N]) solvent: Tz1-PS showed an amazing stability and it exhibited an excellent activity after 2 years when the enzyme was stored in [N221MEM][Tf2N].
- Nishihara,Shiomi,Kadotani,Nokami,Itoh
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supporting information
p. 5250 - 5256
(2017/11/09)
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- De novo protecting-group-free total synthesis of (+)-muricadienin, (+)-ancepsenolide and (+)-3-hexadecyl-5-methylfuran-2(5 H)-one
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A de novo protecting-group-free total synthesis of (+)-muricadienin, (+)-ancepsenolide and (+)-3-hexadecyl-5-methylfuran-2(5H)-one has been achieved. Ring-closing-metathesis has been the key step in the synthesis. In (+)-muricadienin synthesis, a long chain alkyl group has been installed by an sp-sp3 Sonogashira type reaction followed by a cis-selective Lindlar reduction. The total synthesis is achieved in 7 steps and in excellent 43.5% overall yield. Similarly, (+)-ancepsenolide and (+)-3-hexadecyl-5-methylfuran-2(5H)-one synthesis is completed in 5 steps each and in 48 and 68% overall yields, respectively.
- Kunkalkar, Rupesh A.,Laha, Debasish,Fernandes, Rodney A.
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p. 9072 - 9079
(2016/10/07)
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- Third-Generation Amino Acid Furanoside-Based Ligands from d-Mannose for the Asymmetric Transfer Hydrogenation of Ketones: Catalysts with an Exceptionally Wide Substrate Scope
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A modular ligand library of α-amino acid hydroxyamides and thioamides was prepared from 10 different N-tert-butyloxycarbonyl-protected α-amino acids and three different amino alcohols derived from 2,3-O-isopropylidene-α-d-mannofuranoside. The ligand library was evaluated in the half-sandwich ruthenium- and rhodium-catalyzed asymmetric transfer hydrogenation of a wide array of ketone substrates, including simple as well as sterically demanding aryl alkyl ketones, aryl fluoroalkyl ketones, heteroaromatic alkyl ketones, aliphatic, conjugated and propargylic ketones. Under the optimized reaction conditions, secondary alcohols were obtained in high yields and in enantioselectivities up to >99%. The choice of ligand/catalyst allowed for the generation of both enantiomers of the secondary alcohols, where the ruthenium-hydroxyamide and the rhodium-thioamide catalysts act complementarily towards each other. The catalytic systems were also evaluated in the tandem isomerization/asymmetric transfer hydrogenation of racemic allylic alcohols to yield enantiomerically enriched saturated secondary alcohols in up to 98% ee. Furthermore, the catalytic tandem α-alkylation/asymmetric transfer hydrogenation of acetophenones and 3-acetylpyridine with primary alcohols as alkylating and reducing agents was studied. Secondary alcohols containing an elongated alkyl chain were obtained in up to 92% ee. (Figure presented.).
- Margalef, Jèssica,Slagbrand, Tove,Tinnis, Fredrik,Adolfsson, Hans,Diéguez, Montserrat,Pàmies, Oscar
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p. 4006 - 4018
(2016/12/30)
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- Accessing Both Retention and Inversion Pathways in Stereospecific, Nickel-Catalyzed Miyaura Borylations of Allylic Pivalates
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We have developed a stereospecific, nickel-catalyzed Miyaura borylation of allylic pivalates, which delivers highly enantioenriched α-stereogenic γ-aryl allylboronates with good yields and regioselectivities. Our complementary sets of conditions enable access to either enantiomer of allylboronate product from a single enantiomer of readily prepared allylic pivalate substrate. Excellent functional group tolerance, yields, regioselectivities, and stereochemical fidelities are observed. The stereochemical switch from stereoretention to stereoinversion largely depends upon solvent and can be explained by competitive pathways for the oxidative addition step. Our mechanistic investigations support a stereoretentive pathway stemming from a directed oxidative addition and a stereoinvertive pathway that is dominant when MeCN blocks coordination of the directing group by binding the nickel catalyst.
- Zhou, Qi,Srinivas, Harathi D.,Zhang, Songnan,Watson, Mary P.
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p. 11989 - 11995
(2016/10/07)
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- Switchable asymmetric bio-epoxidation of α,β-unsaturated ketones
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Efficient asymmetric bio-epoxidation of electron-deficient α,β-unsaturated ketones was realized via a tandem reduction-epoxidation-dehydrogenation cascade, which proceeds in a switchable manner to afford either chiral epoxy ketones or allylic epoxy alcoho
- Liu, Yu-Chang,Wu, Zhong-Liu
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p. 1158 - 1161
(2016/01/15)
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- Zinc-Catalyzed Enantioselective Hydrosilylation of Ketones and Imines under Solvent-Free Conditions
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The zinc acetate promoted asymmetric hydrosilylation of various ketones and imines under solvent-free conditions was examined by using an unprecedented low catalyst loading. Exposure of ketones to 0.05 mol % Zn-based chiral diamine complex in the presence of triethoxysilane afforded enantioenriched alcohols in excellent yields (up to 98 %) and enantioselectivities (up to 97 % ee). This methodology also allowed for the chemoselective 1,2-reduction of α,β-unsaturated ketones and imines.
- Szewczyk, Marcin,Bez?ada, Agata,Mlynarski, Jacek
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p. 3575 - 3579
(2016/12/14)
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- Spatial effects of oxovanadium-immobilized mesoporous silica on racemization of alcohols and application in lipase-catalyzed dynamic kinetic resolution
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We recently reported a new dynamic kinetic resolution (DKR) method based on the combination of lipase-catalyzed kinetic resolution of racemic alcohols and the V-MPS3-catalyzed in situ racemization of less reactive alcohol enantiomers. In V-MPS3, oxovanadium moieties were covalently bound to the inner surface of mesoporous silica (MPS) with a pore size of about 3 nm. The catalytic activity of V-MPS3 was much higher than that of related vanadium compounds; however, we could neither explain its unusually high activity nor confirm that the racemization predominantly occurred inside the V-MPS pores. Therefore, in this study, we prepared V-MPS2 and V-MPS4 from the corresponding MPS with pore diameters of approximately 2 nm and 4 nm, respectively and compared their racemization activities with that of V-MPS3 using some optically active alcohols with different molecular sizes and polarities. We discovered a positive correlation between the pore size of V-MPS and substrate racemization rate as well as the high polarity of the MPS pores. The results suggested that the racemization predominantly occurs in the pores of V-MPS and that a small pore size (2-4 nm) is essential to generate the polar environment of V-MPS, which probably accelerates the racemization by facilitating the C-O bond cleavage of the vanadate intermediates. Using V-MPS with a pore size suitable for each substrate, lipase/oxovanadium combo-catalyzed DKR could be applied to a wider range of alcohols including allyl alcohols, benzylic alcohols, and propargyl alcohols to give the corresponding esters in excellent isolated yields and enantioselectivities.
- Sugiyama, Koji,Oki, Yasuhiro,Kawanishi, Shinji,Kato, Katsuya,Ikawa, Takashi,Egi, Masahiro,Akai, Shuji
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p. 5023 - 5030
(2016/07/11)
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- Enantioselective addition of organozinc reagents to carbonyl compounds catalyzed by a camphor derived chiral γ-amino thiol ligand
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In this article, the design and synthesis of the chiral camphor derived γ-amino thiol ligand 17 and its application in catalytic enantioselective carbon-carbon forming reactions through the addition of organozinc reagents to carbonyl compounds is described. The catalytic activity and enantioselectivity of ligand 17 is demonstrated in the enantioselective addition of various organozinc reagents to aldehydes and ketoesters, offering the corresponding alcohols in high yields and enantioselectivities. The role of the mercapto group in the highly enantioselective 1,2-addition reaction of organozincs to aldehyde is also discussed.
- Wu, Hsyueh-Liang,Wu, Ping-Yu,Cheng, Ying-Ni,Uang, Biing-Jiun
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p. 2656 - 2665
(2016/05/10)
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- Iron(II)/(NH)2P2 Macrocycles: Modular, Highly Enantioselective Transfer Hydrogenation Catalysts
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A generalized protocol for the synthesis of chiral (NH)2P2 macrocycles allows changing the linker between the phosphines and gives access to a family of such ligands, as demonstrated for the propane-1,3-diyl analogue. The corresponding complexes based on earth-abundant and nontoxic iron were applied as catalysts in the asymmetric transfer hydrogenation of polar double bonds. Thanks to the ligand modularity and to the use of tunable isonitriles as ancillary ligands, the catalyst system can be individually optimized for each substrate to give high enantioselectivity (up to 99.9% conversion and 99.6% ee, TOF up to >3950 h-1) for a broad scope of 26 substrates.
- Bigler, Raphael,Huber, Raffael,St?ckli, Marco,Mezzetti, Antonio
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p. 6455 - 6464
(2016/10/18)
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- Characterization of the monolignol oxidoreductase AtBBE-like protein 15 L182V for biocatalytic applications
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Monolignol oxidoreductases from the berberine bridge enzyme-like (BBE-like) protein family (pfam 08031) catalyze the oxidation of monolignols to the corresponding aldehydes. In this report, we explore the potential of a monolignol oxidoreductase from Arabidopsis thaliana (AtBBE-like protein 15) as biocatalyst for oxidative reactions. For this study we employed a variant with enhanced reactivity towards oxygen, which was obtained by a single amino acid exchange (L182V). The pH and temperature optima of the purified AtBBE-like protein 15 L182V were determined as well as the tolerance toward organic co-solvents; furthermore the substrate scope was characterized. The enzyme has a temperature optimum of 50 °C and retains more than 50% activity between pH 5 and pH 10 within 5 min. The enzyme shows increased activity in the presence of various co-solvents (10–50% v/v), including acetonitrile, 2-propanol, 1,4-dioxane, and dimethyl sulfoxide. Primary benzylic and primary or secondary allylic alcohols were accepted as substrates. The enantioselectivity E in the oxidation of secondary alcohols was good to excellent (E>34 to?>200).
- Pils, Sabine,Schnabl, Kordula,Wallner, Silvia,Daniel, Bastian,Macheroux, Peter,Kljajic, Marko,Kupresanin, Nina,Breinbauer, Rolf,Fuchs, Michael,Rocha, Raquel,Schrittwieser, Joerg H.,Kroutil, Wolfgang
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- Catalytic enantioselective addition of methyltriisopropoxititanium to aldehydes
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An efficient catalyst for the enantioselective synthesis of chiral methyl carbinols from aldehydes is presented. The system uses methyltriisopropoxytitanium as a nucleophile and a readily available binaphthyl derivative as a chiral ligand. The enantioselective methylation of both aromatic and aliphatic aldehydes proceeds with good yields and high enantioselectivities under mild conditions.
- Veguillas, Marcos,Solà, Ricard,Fernández-Iba?ez, M. ángeles,Maciá, Beatriz
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p. 643 - 648
(2016/07/11)
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- Catalytic Asymmetric Addition of Organolithium Reagents to Aldehydes
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Herein we report an efficient catalytic system for the titanium-promoted enantioselective addition of organolithium reagents to aldehydes, based on chiral Ar-BINMOL ligands. Unprecedented yields and enantioselectivities are achieved in the alkylation reactions of aliphatic aldehydes. Remarkably, methyllithium can be added to a wide variety of aromatic and aliphatic aldehydes, providing versatile chiral methyl carbinol units in a simple one-pot procedure under mild conditions and in very short reaction times.
- Veguillas, Marcos,Solà, Ricard,Shaw, Luke,Maciá, Beatriz
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p. 1788 - 1794
(2016/04/05)
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