- 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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- Nickel-Mediated Enantiospecific Silylation via Benzylic C-OMe Bond Cleavage
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Benzylic stereocenters are found in bioactive and drug molecules, as enantiopure benzylic alcohols have been used to build such a stereogenic center, but are limited to the construction of a C-C bond. Silylation of alkyl alcohols has the potential to build bioactive molecules and building blocks; however, the development of such a process is challenging and unknown. Herein, we describe an unprecedented AgF-assisted nickel catalysis in the enantiospecific silylation of benzylic ethers.
- Balakrishnan, Venkadesh,Murugesan, Vetrivelan,Chindan, Bincy,Rasappan, Ramesh
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supporting information
p. 1333 - 1338
(2021/02/20)
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- Bu4NHSO4-Catalyzed Direct N-Allylation of Pyrazole and its Derivatives with Allylic Alcohols in Water: A Metal-Free, Recyclable and Sustainable System
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Allylic amines are valuable and functional building blocks. Direct N-allylation of pyrazole and its derivatives as an atom economic strategy to provide allylic amines has been achieved only using commercial Bu4NHSO4 as the metal-free catalyst and water as the solvent without any additives. 11–93% isolated yields were obtained for the N-allylation of pyrazole and its derivatives with allylic alcohols. Bu4NHSO4 could be reused for six times by simple extraction nearly without loss of catalytic activity and was also suitable for a gram-scale production. The reaction of allylic ether and pyrazole did not occur to give the desired product indicated that allylic ether was not the active intermediate in the pathway. Density functional theory (DFT) calculations reveal that there are hydrogen bonding effects among substrates, solvent and catalyst, especially the one formed between allylic alcohol and H2O. Control experiments in different protic solvents further demonstrate the intermolecular hydrogen bonding of allylic alcohol and water. (Figure presented.).
- Zhuang, Hongfeng,Lu, Nan,Ji, Na,Han, Feng,Miao, Chengxia
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p. 5461 - 5472
(2021/09/29)
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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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- Simpler and Cleaner Synthesis of Variously Capped Cobalt Nanocrystals Applied in the Semihydrogenation of Alkynes
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Unlike the classical organometallic approach, we report here a synthetic pathway requiring no reducing sources or heating to produce homogeneous hexagonal-close-packed cobalt nanocrystals (Co NCs). Involving a disproportionation process, this simple and fast (6 min) synthesis is performed at room temperature in the presence of ecofriendly fatty alcohols to passivate Co NCs. Through a recycling step, the yield of Co NCs is improved and the waste generation is limited, making this synthetic route cleaner. After an easy exchange of the capping ligands, we applied them as unsupported catalysts in the stereoselective semihydrogenation of alkynes.
- Moisset, A.,Petit, C.,Petit, M.,Salzemann, C.,Sodreau, A.,Vivien, A.
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supporting information
p. 13972 - 13978
(2020/10/09)
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- Lithium Bromide/HBpin: A Mild and Effective Catalytic System for the Selective Hydroboration of Aldehydes and Ketones
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The catalytic hydroboration of aldehydes and ketones with HBpin was examined using simple and commercially available metal salts (Li, Na, and K). Among the tested salts, LiBr (0.5–1.0 mol%) was found to be an efficient catalyst for the hydroboration of various aldehydes and ketones at room temperature. Further, the chemoselective hydroboration of aldehydes over ketones was also demonstrated.
- An, Duk Keun,Choi, Hyeon Seong,Hwang, Hyonseok,Kim, Hanbi,Lee, Ji Hye,Shin, Hye Lim,Yi, Jaeeun
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p. 1009 - 1018
(2020/10/12)
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- Photocontrolled Cobalt Catalysis for Selective Hydroboration of α,β-Unsaturated Ketones
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Selectivity between 1,2 and 1,4 addition of a nucleophile to an α,β-unsaturated carbonyl compound has classically been modified by the addition of stoichiometric additives to the substrate or reagent to increase their “hard” or “soft” character. Here, we demonstrate a conceptually distinct approach that instead relies on controlling the coordination sphere of a catalyst with visible light. In this way, we bias the reaction down two divergent pathways, giving contrasting products in the catalytic hydroboration of α,β-unsaturated ketones. This includes direct access to previously elusive cyclic enolborates, via 1,4-selective hydroboration, providing a straightforward and stereoselective route to rare syn-aldol products in one-pot. DFT calculations and mechanistic experiments confirm two different mechanisms are operative, underpinning this unusual photocontrolled selectivity switch.
- Beltran, Frédéric,Bergamaschi, Enrico,Funes-Ardoiz, Ignacio,Teskey, Christopher J.
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supporting information
p. 21176 - 21182
(2020/09/17)
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- Capturing the Monomeric (L)CuH in NHC-Capped Cyclodextrin: Cavity-Controlled Chemoselective Hydrosilylation of α,β-Unsaturated Ketones
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The encapsulation of copper inside a cyclodextrin capped with an N-heterocyclic carbene (ICyD) allowed both to catch the elusive monomeric (L)CuH and a cavity-controlled chemoselective copper-catalyzed hydrosilylation of α,β-unsaturated ketones. Remarkably, (α-ICyD)CuCl promoted the 1,2-addition exclusively, while (β-ICyD)CuCl produced the fully reduced product. The chemoselectivity is controlled by the size of the cavity and weak interactions between the substrate and internal C?H bonds of the cyclodextrin.
- Bistri-Aslanoff, Olivia,Derat, Etienne,Leloux, Sébastien,Leyssens, Tom,Ménand, Micka?l,Meijide Suárez, Jorge,Riant, Olivier,Roland, Sylvain,Sollogoub, Matthieu,Xu, Guangcan,Zhang, Pinglu,Zhang, Yongmin
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supporting information
p. 7591 - 7597
(2020/03/23)
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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.
- -
-
Paragraph 0063-0066; 0069-0077
(2020/01/03)
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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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- HFIP Solvent Enables Alcohols to Act as Alkylating Agents in Stereoselective Heterocyclization
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A new method for the stereoselective synthesis of highly functionalized oxygen heterocycles using allyl or benzyl alcohols as alkylating agents is presented. The process is efficient and atom economic, generating water as the only stoichiometric byproduct. Substoichiometric amounts of Ti(OiPr)4 in HFIP solvent are key to this reactivity, and the method tolerates a broad substitution pattern on both the alcohol initiator and homoallylic alcohol substrate. Preliminary mechanistic studies reveal in situ formation of a titanium complex with HFIP which may initiate the cyclization reaction. Further stereoselective functionalization of the products allows access to a diverse range of interesting heterocyclic structures.
- Zhu, Yuxiang,Colomer, Ignacio,Thompson, Amber L.,Donohoe, Timothy J.
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supporting information
p. 6489 - 6493
(2019/05/06)
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- Practical and selective hydroboration of aldehydes and ketones in air catalysed by an iron(ii) coordination polymer
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The in air catalytic hydroboration of ketones and aldehydes with pinacolborane by an iron(ii) coordination polymer (CP) is carried out under mild and solvent-free conditions. The precatalyst is highly active towards a wide range of substrates including functionalized ketones and aldehydes in the presence of KOtBu as an activator, achieving a high turnover number (TON) of up to 9500. Excellent chemoselectivity to aldehydes over ketones was also revealed, which is in sharp contrast with the results obtained under inert atmosphere using the same catalyst system. This catalyst observed here is not only highly efficient but also recyclable for reuse for at least 5 times without losing its effectiveness.
- Zhang, Guoqi,Cheng, Jessica,Davis, Kezia,Bonifacio, Mary Grace,Zajaczkowski, Cynthia
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p. 1114 - 1121
(2019/03/12)
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- Chemoselective Luche-Type Reduction of α,β-Unsaturated Ketones by Magnesium Catalysis
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The chemoselective reduction of α,β-unsaturated ketones by use of an economic and readily available Mg catalyst has been developed. Excellent yields for a wide range of ketones have been achieved under mild reaction conditions, short times, and low catalyst loadings (0.2-0.5 mol %).
- Jang, Yoon Kyung,Magre, Marc,Rueping, Magnus
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supporting information
p. 8349 - 8352
(2019/10/16)
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- Synthesis of Allylsilanes via Nickel-Catalyzed Cross-Coupling of Silicon Nucleophiles with Allyl Alcohols
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NiCl2(PMe3)2-catalyzed reaction of allyl alcohols with silylzinc reagents, including PhMe2SiZnCl, Ph2MeSiZnCl, and Ph3SiZnCl, was performed, achieving allylsilanes in high yields. Aryl- and heteroaryl-substituted allyl alcohols, (E)-3-arylprop-2-en-1-ols, 1-aryl-prop-2-en-1-ols, and (E)-1-phenylpent-1-en-3-ol can be employed in the transformation. A range of functional groups as well as heteroaryl groups were tolerated. Reaction exhibited high regioselectivity and E/Z-selectivity when 1- or 3-aryl-substituted allyl alcohols were used as the substrates. Reaction of chiral allyl alcohol, (S,E)-1-phenylpent-1-en-3-ol, yielded a configuration-inversion product (R,E)-dimethyl(phenyl)(1-phenylpent-1-en-3-yl)silane.
- Yang, Bo,Wang, Zhong-Xia
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supporting information
p. 7965 - 7969
(2019/10/19)
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- Palladium-catalyzed regioselective hydroboration of aryl alkenes with B2pin2
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A palladium(ii)-catalyzed hydroboration of aryl alkenes with stable and easy-to-handle (pinacolato)diboron (B2pin2) under mild conditions has been developed. Acetic acid acted as the solvent and the hydrogen source, which has been identified by deuterium experiments. Notably, isomerization-hydroboration of allyl benzene derivatives was observed. As a result, a series of benzyl boronic esters were obtained in moderate to excellent yields with exclusive regioselectivity.
- Huang, Jiuzhong,Yan, Wuxin,Tan, Chaowei,Wu, Wanqing,Jiang, Huanfeng
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supporting information
p. 1770 - 1773
(2018/02/21)
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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 18; 21
(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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- Nickel-Catalyzed Direct Coupling of Allylic Alcohols with Organoboron Reagents
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The direct coupling of allylic alcohols with arylboronic acids or their derivatives catalyzed by Ni(cod)2 in the presence of a catalytic amount of base has been developed. A wide variety of allylic substrates or arylboronic acids turned out to be applicable to this catalytic system. The present method does not require the use of ligands for stabilizing the nickel catalyst in most cases or additional activators for activation of allylic alcohols.
- Wang, Gaonan,Gan, Yi,Liu, Yuanhong
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supporting information
p. 916 - 920
(2018/09/22)
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- Synthesis, characterization, and investigations of antimicrobial activity of benzopyrans, benzofurans and spiro[4.5]decanes
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In this study, the radical cyclization reactions of cyclic 1,3-dicarbonyl compounds (1a–c) and α,β-unsaturated alcohols (2a–d) through Mn(OAc)3 were performed. A series of biologically interesting dihydropyrans (3–5) and dihydrofurans (6–18) were synthesized as a result of these reactions. Spiro compounds (19–20) were obtained from the reactions of 1,3-dicarbonyl compounds and (E)-2,4-diphenyl-but-3-en-2-ol (2e). The unique structure of compound 19 was also confirmed by X-ray crystallography. In addition, the antibacterial activities of synthesized compounds were screened against some bacteria. Their zone diameters showed better results than some known antibiotics.
- Akp?nar, Deniz E.,?zgür (Nee Yakut), Mehtap,Aslan, Hakan,Alag?z, O?uzhan,?ktemer, Atilla,Dal, Hakan,H?kelek, Tuncer,Lo?o?lu, Elif
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p. 2510 - 2521
(2018/10/24)
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- Rapid Access to Thiolactone Derivatives through Radical-Mediated Acyl Thiol-Ene and Acyl Thiol-Yne Cyclization
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A new synthetic approach to thiolactones that employs an efficient acyl thiol-ene (ATE) or acyl thiol-yne (ATY) cyclization to convert unsaturated thiocarboxylic acid derivatives into thiolactones under very mild conditions is described. The high overall yields, fast kinetics, high diastereoselectivity, excellent regiocontrol, and broad substrate scope of these reaction processes render this a very useful approach for diversity-oriented synthesis and drug discovery efforts. A detailed computational rationale is provided for the observed regiocontrol.
- McCourt, Ruairi O.,Dénès, Fabrice,Sanchez-Sanz, Goar,Scanlan, Eoin M.
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supporting information
p. 2948 - 2951
(2018/05/28)
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- Pyrrolidines and Piperidines by Ligand-Enabled Aza-Heck Cyclizations and Cascades of N-(Pentafluorobenzoyloxy)carbamates
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Ligand-enabled aza-Heck cyclizations and cascades of N-(pentafluorobenzoyloxy)carbamates are described. These studies encompass the first examples of efficient non-biased 6-exo aza-Heck cyclizations. The methodology provides direct and flexible access to carbamate protected pyrrolidines and piperidines.
- Hazelden, Ian R.,Carmona, Rafaela C.,Langer, Thomas,Pringle, Paul G.,Bower, John F.
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supporting information
p. 5124 - 5128
(2018/03/26)
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- Half-Sandwich Ruthenium Carbene Complexes Link trans-Hydrogenation and gem-Hydrogenation of Internal Alkynes
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The hydrogenation of internal alkynes with [Cp?Ru]-based catalysts is distinguished by an unorthodox stereochemical course in that E-alkenes are formed by trans-delivery of the two H atoms of H2. A combined experimental and computational study now provides a comprehensive mechanistic picture: a metallacyclopropene (??2-vinyl complex) is primarily formed, which either evolves into the E-alkene via a concerted process or reacts to give a half-sandwich ruthenium carbene; in this case, one of the C atoms of the starting alkyne is converted into a methylene group. This transformation represents a formal gem-hydrogenation of a ?€-bond, which has hardly any precedent. The barriers for trans-hydrogenation and gem-hydrogenation are similar: whereas DFT predicts a preference for trans-hydrogenation, CCSD(T) finds gem-hydrogenation slightly more facile. The carbene, once formed, will bind a second H2 molecule and evolve to the desired E-alkene, a positional alkene isomer or the corresponding alkane; this associative pathway explains why double bond isomerization and over-reduction compete with trans-hydrogenation. The computed scenario concurs with para-hydrogen-induced polarization transfer (PHIP) NMR data, which confirm direct trans-delivery of H2, the formation of carbene intermediates by gem-hydrogenation, and their evolution into product and side products alike. Propargylic aOR (R = H, Me) groups exert a strong directing and stabilizing effect, such that several carbene intermediates could be isolated and characterized by X-ray diffraction. The gathered information spurred significant preparative advances: specifically, highly selective trans-hydrogenations of propargylic alcohols are reported, which are compatible with many other reducible functional groups. Moreover, the ability to generate metal carbenes by gem-hydrogenation paved the way for noncanonical hydrogenative cyclopropanations, ring expansions, and cycloadditions.
- Guthertz, Alexandre,Leutzsch, Markus,Wolf, Lawrence M.,Gupta, Puneet,Rummelt, Stephan M.,Goddard, Richard,Farès, Christophe,Thiel, Walter,Fürstner, Alois
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supporting information
p. 3156 - 3169
(2018/03/08)
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- A catalytic allylic cation-induced intermolecular allylation-semipinacol rearrangement
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A catalytic intermolecular semipinacol rearrangement induced by allylic carbocations has been realized. This tandem reaction is highly efficient under the catalysis of ZnBr2, generating a wide range of α-homoallyl substituted ketones which contain all-carbon quaternary centres in good to excellent yields (up to 98%) with moderate to high diastereoselectivities (up to >20?:?1). Synthetic application of this novel methodology in the construction of core structures of natural products is also reported.
- Xu, Ming-Hui,Dai, Kun-Long,Tu, Yong-Qiang,Zhang, Xiao-Ming,Zhang, Fu-Min,Wang, Shao-Hua
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p. 7685 - 7688
(2018/07/15)
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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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- Silver-catalyzed decarboxylative C(sp2)-C(sp3) coupling reactions: Via a radical mechanism
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A silver catalyzed decarboxylative C(sp2)-C(sp3) coupling of vinylic carboxylic acids with alcohols, alkylbenzenes, cycloalkanes and cyclic ethers was developed by using DTBP as an oxidant. This reaction tolerates a wide range of substrates, and products are obtained in good to excellent yields. The reaction also shows good stereoselectivity, and only trans-isomers are obtained. In addition, a radical pathway would be involved to facilitate this decarboxylative C(sp2)-C(sp3) coupling reaction.
- Fang, Zhongxue,Wei, Chenlong,Lin, Jing,Liu, Zhenhua,Wang, Wei,Xu, Chenshu,Wang, Xuemin,Wang, Yu
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supporting information
p. 9974 - 9978
(2017/12/26)
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- VINYLOGOUS PHENETHYLAMINES AS NEUROTRANSMITTER RELEASERS
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The disclosure provides monoamine neurotransmitter releaser and/or monoamine uptake inhibitor compounds having biogenic amine transporter activity but lacking substantial activity at 5-HT2 receptor subtypes. The phenethylamine or vinylogous phe
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Paragraph 00157; 00158
(2017/12/02)
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- HYDROGENATION OF ALDEHYDE OR KETONE COMPOUNDS WITH FE/TRIDENTATE LIGANDS COMPLEXES
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The present invention relates to the field of catalytic hydrogenation and, more particularly, to the use of Fe complexes with tridentate ligands, having one amino or imino coordinating group and two phosphino coordinating groups, in hydrogenation processes for the reduction of ketones or aldehydes, into the corresponding alcohol or diol, respectively.
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Page/Page column 25-27
(2017/01/02)
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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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- 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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- Evaluation of Fe and Ru Pincer-Type Complexes as Catalysts for the Racemization of Secondary Benzylic Alcohols
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Fe and Ru pincer-type catalysts are used for the racemization of benzylic alcohols. Racemization with the Fe catalyst was achieved within 30 minutes under mild reaction conditions, with a catalyst loading as low as 2 mol %. This reaction constitutes the first example of an iron-catalyzed racemization of an alcohol. The efficiency for racemization of the Fe catalyst and its Ru analogue was evaluated for a wide range of sec-benzylic alcohols. The commercially available Ru complex proved to be highly robust and even tolerated the presence of water in the reaction mixture.
- Bornschein, Christoph,Gustafson, Karl P. J.,Verho, Oscar,Beller, Matthias,B?ckvall, Jan-E.
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p. 11583 - 11586
(2016/08/05)
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- Diverse N-Heterocyclic Ring Systems via Aza-Heck Cyclizations of N-(Pentafluorobenzoyloxy)sulfonamides
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Aza-Heck cyclizations initiated by oxidative addition of Pd0-catalysts into the N?O bond of N-(pentafluoro-benzoyloxy)sulfonamides are described. These studies, which encompass only the second class of aza-Heck reaction developed to date, provide direct access to diverse N-heterocyclic ring systems.
- Hazelden, Ian R.,Ma, Xiaofeng,Langer, Thomas,Bower, John F.
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supporting information
p. 11198 - 11202
(2016/10/13)
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- The biogenic amine transporter activity of vinylogous amphetamine analogs
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A series of vinylogous amphetamine analogs was synthesized and examined for their activity at biogenic amine transporters and serotonin-2 receptor (5-HT2) subtypes. (1S,3E)-1-Methyl-4-phenyl-but-3-enylamine (S-6) is a potent dual dopamine/serotonin (DA/5-HT) releaser with no activity at 5-HT2 receptors. This unique profile of actions suggests that analog S-6 is a viable lead compound for identifying new structural classes of DA/5-HT releasers with therapeutic benefit and reduced abuse liability.
- Decker, Ann M.,Partilla, John S.,Baumann, Michael H.,Rothman, Richard B.,Blough, Bruce E.
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supporting information
p. 1657 - 1663
(2016/08/24)
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- Kinetic Resolution of Unsymmetrical Acyclic Allyl Carbonates Using Trimethylsilyl Cyanide via Palladium-Catalyzed Asymmetric Allylic Alkylation
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The kinetic resolution of 1,3-disubstituted unsymmetrical allylic substrates with TMSCN as the nucleophile was realized via palladium-catalyzed asymmetric allylic alkylation, providing optically active allylic substrates and β,γ-unsaturated nitriles in good yield and enantioselectivity.
- Bai, Da-Chang,Wang, Wan-Ying,Ding, Chang-Hua,Hou, Xue-Long
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supporting information
p. 1510 - 1514
(2015/06/30)
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- An unsymmetrical iron catalyst for the asymmetric transfer hydrogenation of ketones
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A new iron(II)(Ph2P-NH-N-PCy2) complex with a dicyclohexylphosphino group trans to the NH group was found to catalyze the asymmetric transfer hydrogenation of a variety of ketones with high enantioselectivity.
- Smith, Samantha A.M.,Morris, Robert H.
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supporting information
p. 1775 - 1779
(2015/06/16)
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- Improving the properties of bacterial r-selective hydroxynitrile lyases for industrial applications
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Hydroxynitrile lyases (HNLs) catalyse the reversible cleavage of cyanohydrins to carbonyl compounds and HCN. The recent discovery of bacterial HNLs with a cupin fold gave rise to a new promising class of these enzymes. They are interesting candidates for the synthesis of cyanohydrins on an industrial scale owing to their high expression levels in Escherichia coli. The activity and enantioselectivity of the manganese-dependent HNL from Granulicella tundricola (GtHNL) were significantly improved by site-saturation mutagenesis of active site amino acids. The combination of beneficial mutations resulted in a variant with 490-fold higher specific activity in comparison to the wild-type enzyme. More importantly, GtHNL-A40H/V42T/Q110H is a highly competitive alternative for the synthesis of chiral cyanohydrins, such as 2-chlorobenzaldehyde cyanohydrin, (R)-2-hydroxy-4-phenylbutyronitrile, and (R)-2-hydroxy-4-phenyl-3-butene nitrile, which serve as intermediates for the synthesis of pharmaceuticals.
- Wiedner, Romana,Kothbauer, Bettina,Pavkov-Keller, Tea,Gruber-Khadjawi, Mandana,Gruber, Karl,Schwab, Helmut,Steiner, Kerstin
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p. 325 - 332
(2015/03/05)
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- Asymmetric hydrogenation of benzalacetone catalyzed by TPPTS-stabilized Ru in ionic liquids
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Achiral monophosphine TPPTS [TPPTS: P(m-C6H4SO3Na)3]-stabilized Ru was successfully applied to catalyze the asymmetric hydrogenation of benzalacetone in ionic liquids using (S,S)-DPENDS [disodium salt of sulfonated (S,S)-1,2-diphenyl-1,2-ethylenediamine] as chiral modifier. Under the optimized reaction conditions, the conversion of benzalacetone, chemoselectivity, and enantioselectivity of 4-phenyl-3-buten-2-ol could be reached up to 99.5%, 98.8%, and 74.6%, respectively. The TPPTS-stabilized Ru catalyst immobilized in ionic liquids could be easily separated from the resulting products by extraction with n-hexane, which could be recycled and reused five times without significant loss in activity, chemoselectivity, and enantioselectivity.
- Wang, Jinbo,Qin, Ruixiang,Xiong, Wei,Liu, Derong,Feng, Jian
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p. 834 - 838
(2015/03/05)
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- One-Carbon Homologation of Primary Alcohols and the Reductive Homologation of Aldehydes Involving a Jocic-Type Reaction
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(Trichloromethyl)carbinols, which are formed in one operation from either alcohols or aldehydes, can be converted into primary alcohols in a Jocic-type reaction involving LiBH4. The net result is a convenient two-step, one-carbon homologation of primary alcohols or a reductive one-carbon homologation of aldehydes featuring a broad substrate scope. The method is step-economical, and it nicely complements established one-carbon homologation strategies. (Trichloromethyl)carbinols, which are formed in one operation from either alcohols or aldehydes, can be converted into primary alcohols in a Jocic-type reaction involving LiBH4. The net result is a convenient two-step, one-carbon homologation of primary alcohols or a reductive one-carbon homologation of aldehydes featuring a broad substrate scope.
- Li, Zhexi,Gupta, Manoj K.,Snowden, Timothy S.
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p. 7009 - 7019
(2015/11/16)
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- Chemo-, regio-, and stereoselective Heck-Matsuda arylation of allylic alcohols under mild conditions
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Heck arylation with allylic alcohol is extremely challenging due to chemo-, regio-, and stereoselective scrambling. Here we report a mild protocol for the alcohol selective β- and α-arylation of allylic and cinnamyl alcohols respectively with aryldiazonium salts. The steric and electronic parameters of the alkene play a prominent role in the regioselectivity.
- Chaudhari, Tohasib Yusub,Hossian, Asik,Manna, Manash Kumar,Jana, Ranjan
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supporting information
p. 4841 - 4845
(2015/05/05)
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- Oxidative cleavage of allyl ethers by an oxoammonium salt
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A method to oxidatively cleave allyl ethers to their corresponding aldehydes mediated by an oxoammonium salt is described. Using a biphasic solvent system and mild heating, cleavage proceeds readily, furnishing a variety of α,β-unsaturated aldehydes and ketones.
- Kelly, Christopher B.,Ovian, John M.,Cywar, Robin M.,Gosselin, Taylor R.,Wiles, Rebecca J.,Leadbeater, Nicholas E.
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p. 4255 - 4259
(2015/04/14)
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- Eco-friendly stereoselective reduction of α,β-unsaturated carbonyl compounds by Er(OTf)3/NaBH4 in 2-MeTHF
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An operationally simple and environmentally benign catalytic procedure has been developed to selectively reduce different α,β-unsaturated ketones. The corresponding allylic alcohols are obtained with high chemo- and diastereoselectivity using Er(OTf)3 and NaBH4 in 2-MeTHF. This protocol reduces the amount of catalyst and NaBH4 needed, compared to classical procedures and the stages of extraction/purification are carried out in aqueous solutions avoiding the use of toxic solvents. Taking into account that Er(OTf)3 can be considered even less toxic than table salt and the 'greenness' of 2-MeTHF as a solvent, the system Er(OTf)3/2-MeTHF can be proposed as a cheap, efficient, and environmentally sustainable reduction system for the synthesis of allylic alcohols.
- Nardi, Monica,Sindona, Giovanni,Costanzo, Paola,Oliverio, Manuela,Procopio, Antonio
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p. 1132 - 1135
(2015/02/19)
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- Probing the effect of heterocycle-bonding in PNX-type ruthenium pre-catalysts for reactions involving H2
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A series of ruthenium(ii) complexes with three novel PNX-type pincer ligands is reported, in which X denotes a heterocyclic donor group (PNX = Ph2PCH2CH2N(H)CH2-X, X = 2-pyridyl, 2-furanyl, 2-thiophenyl or 2-pyrrolyl). The reaction of [(Ph3P)3RuCl2] with one equivalent of ligand leads to the trans-dichloro complexes [(PNX)RuCl2(PPh3)] (1-4) for all ligands, whereas the complexation of [(Ph3P)3Ru(H)(Cl)(CO)] results in different types of complexes. The variation of the heterocyclic donor group is in line with different binding properties and a labilization of this group. Investigations on the catalytic activity of different types of ruthenium(ii) complexes in hydrogenation and dehydrogenation reactions reveal that more labile bound heterocycle donors result in a decrease of catalytic productivity and activity.
- Xu,Langer
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supporting information
p. 16785 - 16790
(2015/10/05)
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- Pincer-Nickel-Catalyzed Allyl-Aryl Coupling between Allyl Methyl Ethers and Arylzinc Chlorides
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The P,N,N-pincer nickel complex [Ni(Cl){N(2-Ph2PC6H4)(2′-Me2NC6H4)}]-catalyzed allyl-aryl coupling was studied. The reaction of allyl methyl ethers, including (1-methoxyallyl)arenes and (3-methoxyprop-1-en-1-yl)arenes, with arylzinc chlorides afforded linear (E)-alkenes in high yields, whereas the reaction of (E)-1-methoxytridec-2-ene with p-Me2NC6H4ZnCl generated a mixture of linear and branched alkenes.
- Tao, Jian-Long,Yang, Bo,Wang, Zhong-Xia
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p. 12627 - 12634
(2016/01/09)
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