- Chiral cyclometalated iridium complexes for asymmetric reduction reactions
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A series of chiral cyclometalated iridium complexes have been synthesised by cyclometalating chiral 2-aryl-oxazoline and imidazoline ligands with [Cp?IrCl2]2. These iridacycles were studied for asymmetric transfer hydrogenation reactions with formic acid as the hydrogen source and were found to display various activities and enantioselectivities, with the most effective ones affording up to 63% ee in the asymmetric reductive amination of ketones and 77% ee in the reduction of pyridinium ions. This journal is
- Smith, Jennifer,Kacmaz, Aysecik,Wang, Chao,Villa-Marcos, Barbara,Xiao, Jianliang
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supporting information
p. 279 - 284
(2021/01/18)
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- Protic additives or impurities promote imine reduction with pinacolborane
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We report here that addition of stoichiometric amounts of alcohols or water to mixtures of imines and pinacolborane promote reduction reactions. The reactions of several imines were examined, revealing that alkyl imines were reduced, while aniline derived imines were not effectively reduced. The use of binol as an additive resulted in modest enantioinduction, however other chiral additives that were screened gave negligible enantioinduction. While the reactions described herein are not competitive in conversion with established imine reduction technologies, this work reveals that the presence of protic impurities must be considered as a promoter of side reactions in catalyzed imine hydroborations. Amines also promote imine reduction in certain cases, raising the possibility of a slow autocatalytic reaction. The ability of water or other protic impurities to promote the reduction of imines with pinacolborane represents an important identification of a potential source of background reaction in catalyzed reductions of imines.
- Huchenski, Blake S. N.,Speed, Alexander W. H.
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supporting information
p. 1999 - 2004
(2019/02/20)
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- CHIRAL CATALYST AND METHOD FOR ASYMMETRIC REDUCTION OF AN IMINE
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The present disclosure discusses (i) a compound having a chemical formula according to Formula (I), or its enantiomer; and (ii) a compound that is reactive with a hydride to produce a compound having a chemical formula according to Formula (I), or its enantiomer. Formula (I) is: Formula (I) where R1 and R2 are H, optionally substituted C1-C3 alkyl, or linked together to form an optionally substituted C3 or C4 alkyl group; R3 and R3' are H; R4 and R4' are the same, and are optionally substituted C1-C6 alkyl; and R5 and R5' are the same, and are optionally substituted aryl or heteroaryl. In some examples, R4 and R5 are linked, and R4' and R5' are linked, where both linking groups are the same. The present disclosure also discusses methods of asymmetric reduction of an imine, and methods of forming the catalysts and pre-catalysts.
- -
-
Paragraph 00116; 00117
(2019/04/16)
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- Enantioselective Imine Reduction Catalyzed by Phosphenium Ions
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The first use of phosphenium cations in asymmetric catalysis is reported. A diazaphosphenium triflate, prepared in two or three steps on a multigram scale from commercially available materials, catalyzes the hydroboration or hydrosilylation of cyclic imin
- Lundrigan, Travis,Welsh, Erin N.,Hynes, Toren,Tien, Chieh-Hung,Adams, Matt R.,Roy, Kayelani R.,Robertson, Katherine N.,Speed, Alexander W. H.
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supporting information
p. 14083 - 14088
(2019/10/11)
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- Hydroboration Catalyzed by 1,2,4,3-Triazaphospholenes
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The synthesis and study of the catalytic activity of 1,2,4,3-triazaphospholenes (TAPs) is reported. TAPs represent a more modular scaffold than previously reported diazaphospholenes. TAP halides were shown to catalyze the 1,2 hydroboration of 19 imines, and three α,β unsaturated aldehydes with pinacolborane, including examples that did not undergo hydroboration by previously reported diazaphospholene systems. DFT calculations support a mechanism where a triazaphospholene cation interacts with the substrate, a mechanism distinct from diazaphospholene catalyzed hydroborations.
- Tien, Chieh-Hung,Adams, Matt R.,Ferguson, Michael J.,Johnson, Erin R.,Speed, Alexander W. H.
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supporting information
p. 5565 - 5568
(2017/10/25)
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- Asymmetric Imine Hydroboration Catalyzed by Chiral Diazaphospholenes
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The first use of diazaphospholenes as chiral catalysts has been demonstrated with enantioselective imine hydroboration. A chiral diazaphospholene prepared in a simple three-step synthesis from commercial materials has been shown to achieve the highest enantioselectivity for the hydroboration of alkyl imines with pinacolborane reported to date. Enantiomer ratios of up to 88:12 were obtained with low (2 mol %) catalyst loadings. Twenty examples of asymmetric reduction employing this main-group catalysis protocol, including the synthesis of the pharmaceuticals ent-rasagiline and fendiline, are shown.
- Adams, Matt R.,Tien, Chieh-Hung,McDonald, Robert,Speed, Alexander W. H.
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p. 16660 - 16663
(2017/12/13)
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- Iron-catalyzed transfer hydrogenation of imines assisted by an iron-based Lewis acid
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An iron-catalyzed transfer hydrogenation of N-aryl and N-alkyl imines using isopropanol as the hydrogen donor is reported for the first time. A combination of two iron complexes serving different roles is the key for the success of this catalytic system. As a result, an environmentally friendly and precious metal-free transfer hydrogenation of imines has been developed. The use of a suitable co-catalyst as an activator not only led to efficient transfer hydrogenation, but also showed potential in enantioselective transformation.
- Pan, Hui-Jie,Ng, Teng Wei,Zhao, Yu
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supporting information
p. 5490 - 5493
(2016/07/06)
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- Asymmetric Transfer Hydrogenation of Imines using Alcohol: Efficiency and Selectivity are Influenced by the Hydrogen Donor
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The influence of the alcohol, as the hydrogen donor, on the efficiency and selectivity of the asymmetric transfer hydrogenation (ATH) of imines is reported for the first time. This discovery not only leads to a highly enantioselective access to N-aryl and N-alkyl amines, but also provides new insight into the mechanism of the ATH of imines. Both experimental and computational studies provide support for the reaction pathway involving an iridium alkoxide as the reducing species.
- Pan, Hui-Jie,Zhang, Yao,Shan, Chunhui,Yu, Zhaoyuan,Lan, Yu,Zhao, Yu
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supporting information
p. 9615 - 9619
(2016/08/10)
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- A highly active cyclometallated iridium catalyst for the hydrogenation of imines
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A cyclometallated iridium complex containing an imino ligand has been shown to catalyse the hydrogenation of imines. The catalyst is highly active and selective for imino bonds, with a wide variety of imines being hydrogenated in less than 1 hour at a substrate/catalyst (S/C) ratio of 2000 at 20 bar H 2 pressure and 75 °C.
- Villa-Marcos, Barbara,Tang, Weijun,Wu, Xiaofeng,Xiao, Jianliang
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supporting information
p. 6934 - 6939
(2013/10/08)
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- Asymmetric organocatalytic reduction of ketimines with catecholborane employing a N-triflyl phosphoramide Br?nsted acid as catalyst
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The first asymmetric reduction of ketimines with catecholborane employing an enantiopure N-triflyl phosphoramide as the organocatalyst has been developed. Five mole % of the catalyst provides the corresponding secondary amines in very good to almost quantitative yields and good enantioselectivities up to 86:14 e.r. under mild reaction conditions.
- Enders, Dieter,Rembiak, Andreas,Seppelt, Matthias
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p. 470 - 473
(2013/02/23)
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- Asymmetric hydrogenation of N-alkyl and N-aryl ketimines using chiral cationic Ru(diamine) complexes as catalysts: The counteranion and solvent effects, and substrate scope
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Asymmetric hydrogenation of N-alkyl and N-aryl ketimines catalyzed by chiral cationic η6-arene-(N-monosulfonylated diamine) Ru(II) complexes has been investigated. Strong counteranion and solvent effects on the enantioselectivity were observed. The ruthenium catalyst bearing non-coordinating BArF- anion was found to be particularly effective for the hydrogenation of acyclic and exocyclic N-alkyl ketimines in the presence of (Boc)2O in dichloromethane or even under solvent-free conditions, providing chiral amines with up to >99% ee and full conversions. Alternatively, the ruthenium catalyst bearing achiral phosphate anion together with corresponding phosphoric acid as the additive was also efficient for the hydrogenation of N-alkyl ketimines in the absence of (Boc)2O with excellent enantioselectivities and full conversions. For N-aryl ketimines lower enantiomeric excesses were observed by using the ruthenium catalyst bearing BArF- anion. This catalytic protocol thus provides a facile and practical access to optically active amines and has been successfully employed in the gram-scale synthesis of enantiomerically pure (+)-sertraline.
- Chen, Fei,Ding, Ziyuan,He, Yanmei,Qin, Jie,Wang, Tianli,Fan, Qing-Hua
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p. 5248 - 5257
(2012/08/08)
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- Asymmetric synthesis of piperidines and octahydroindolizines using a one-pot ring-closure/N-debenzylation procedure
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The conjugate addition of an enantiopure lithium amide to a ζ-hydroxy-α,β-unsaturated ester followed by a one-pot ring-closure/N-debenzylation protocol has been used in the asymmetric syntheses of (S)-coniine and (R)-δ-coniceine (isolated as the corresponding hydrochloride salts), and (R,R)-1-(hydroxymethyl)octahydroindolizine (the bicyclic fragment of stellettamides A-C).
- Davies, Stephen G.,Fletcher, Ai M.,Hughes, Deri G.,Lee, James A.,Price, Paul D.,Roberts, Paul M.,Russell, Angela J.,Smith, Andrew D.,Thomson, James E.,Williams, Oliver M.H.
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body text
p. 9975 - 9992
(2012/02/15)
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- Reductive amination agents: comparison of Na(CN)BH3 and Si-CBH
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Reductive amination is a chemical reaction commonly employed by organic chemists in academics and the pharmaceutical industry. In this reaction a carbonyl group is converted to an amine via an imine intermediate, the formation of which is rate limiting. A major reagent necessary for the completion of this reaction is a hydride source, commonly sodium cyanoborohydride (Na(CN)BH3). The objective of this research was to compare the efficacy of Na(CN)BH3 with silica-bound cyanoborohydride (Si-CBH) as hydride sources in reductive amination reactions. Work has shown that reactions employing Si-CBH as a hydride source showed significant improvement, exhibiting an average percent conversion 25% greater than reactions using Na(CN)BH3.
- Grenga, Paolo N.,Sumbler, Brittany L.,Beland, Fran?ois,Priefer, Ronny
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scheme or table
p. 6658 - 6660
(2010/03/03)
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- Zinc-catalyzed reduction of imines by triethylsilane
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Low-cost zinc is employed as a catalyst along with triethylsilane (TES) in a simple, straightforward, chemoselective reduction of various aldimines and ketimines to the corresponding secondary amines at room temperature and pressure.
- Kumar, K. Anil,Sreelekha,Shivakumara,Prakasha,Gowda, D. Channe
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experimental part
p. 1332 - 1341
(2009/10/09)
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- A chiral "roofed" cis-diamine-Ru(II) complex: An efficient catalyst for asymmetric transfer hydrogenation of ketimines
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Highly enantioselective transfer hydrogenation of ketimines to the corresponding chiral amines was achieved with the chiral Ru(II) complex, prepared from the conformationally rigid and sterically bulky "roofed" cis-1,2-diamine.
- Matsunaga, Hirofumi,Nakanishi, Kyoko,Nakajima, Makoto,Kunieda, Takehisa,Ishizuka, Tadao
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experimental part
p. 617 - 622
(2009/06/18)
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- 1,1′-Binaphthyldiamine-based lewis bases as readily available and efficient grganocatalysts for the reduction of N-Aryl and N-Alkyl ketimines
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The development of simple, low-cost, efficient, and sustainable routes to enantiomerically pure amines is a topic of extraordinary interest, specially in view of future industrial applications. In this context, we wish to report a chemical and stereochemical efficient synthesis of chiral amines through the Lewis base activated trichlorosilane reduction of ketimines. An organocatalyst, easily prepared in a single step through the condensation of picolinic acid and commercially available 1,1′-binaphthyldiamine, is the key element of this metal-free methodology, that allowed the synthesis of chiral secondary and primary amines in high yields and stereose-lectivity. Noteworthy, such catalysts are able to promote the reduction of N-alkyl ketimines, often in quantitative yield and up to 87% enantioselectivity; it: is worth mentioning that for such transformations only one other organocatalytic system has been reported so far.
- Guizzett, Stefania,Benaglia, Maurizio,Celentano, Giuseppe
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experimental part
p. 3683 - 3687
(2009/12/03)
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- Molecular tweezers for hydrogen: Synthesis, characterization, and reactivity
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The first ansa-aminoborane N-TMPN-CH2C6H4B(C6F5)2 (where TMPNH is 2,2,6,6-tetramethylpiperidinyl) which is able to reversibly activate H2 through an intramolecular mechanism is synthesized. This new substance makes use of the concept of molecular tweezers where the active N and B centers are located close to each other so that one H2 molecule can fit in this void and be activated. Because of the fixed geometry of this ansa-ammonium-borate it forms a short N-H...H-B dihydrogen bond of 1.78 A as determined by X-ray analysis. Therefore, the bound hydrogen can be released above 100 °C. In addition, the short H...H contact and the N-H...H (154°) and B-H...H (125°) angles show that the dihydrogen interaction in N-TMPNH-CH2C6H4BH(C6F5)2 is partially covalent in nature. As a basis for discussing the mechanism, quantum chemical calculations are performed and it is found that the energy needed for splitting H2 can arise from the Coulomb attraction between the resulting ionic fragments, or "Coulomb pays for Heitler-London". The air- and moisture-stable N-TMPNH-CH2C6H4BH(C6F5)2 is employed in the catalytic reduction of nonsterically demanding imines and enamines under mild conditions (110 °C and 2 atm of H2) to give the corresponding amines in high yields. Copyright
- Sumerin, Victor,Schulz, Felix,Atsumi, Michiko,Wang, Cong,Nieger, Martin,Leskelae, Markku,Repo, Timo,Pyykkoe, Pekka,Rieger, Bernhard
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supporting information; experimental part
p. 14117 - 14119
(2009/03/11)
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- Enantioselective hydrosilylation of ketimines with trichlorosilane promoted by chiral N-picolinoylaminoalcohols
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Enantioselective hydrosilylation of N-aryl and N-benzyl ketimines with trichlorosilane catalyzed by readily accessible chiral N-picolinoylaminoalcohols proceeded smoothly furnishing chiral secondary amines in good yields (up to 93%) and moderate to excellent enantioselectivities (up to 95% ee).
- Zheng, Hongjie,Deng, Jingen,Lin, Wenqing,Zhang, Xiaomei
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p. 7934 - 7937
(2008/03/14)
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- Mixtures of chiral phosphorous acid diesters and achiral P ligands in the enantio- and diastereoselective hydrogenation of ketimines
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Try this cocktail! Ligand systems comprising a monodentate phosphorous acid diester derived from binol (La) and an achiral monodentate P ligand (Lb), such as a phosphite, are surprisingly efficient in the stereoselective Ir-catalyzed hydrogenation of ketimines (see scheme).
- Reetz, Manfred T.,Bondarev, Oleg
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p. 4523 - 4526
(2008/09/17)
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- Application of monodentate secondary phosphine oxides, a new class of chiral ligands, in Ir(I)-catalyzed asymmetric imine hydrogenation
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(Matrix presented) Secondary phosphine oxides were prepared from R 1PCl2 and R2MgBr, followed by hydrolysis. They were obtained in an enantiopure form by preparative chiral HPLC. These new monodentate ligands were tested in the iridium-catalyzed hydrogenation of imines at 25 bar. Enantioselectivities up to 76% were obtained at L/lr = 2. Addition of pyridine (Pyr/lr = 1:2) raised the ee to 83%. Using pyridine as an additive allowed reduction of the L/lr ratio to 1 without reduction of ee.
- Jiang, Xiao-Bin,Minnaard, Adriaan J.,Hessen, Bart,Feringa, Ben L.,Duchateau, Alexander L. L.,Andrien, Jean G. O.,Boogers, Jeroen A. F.,De Vries, Johannes G.
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p. 1503 - 1506
(2007/10/03)
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- Synthesis of α-methyl kainic acid by stereospecific lithiation-dearomatizing cyclization of a chiral benzamide
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Stereospecific lithiation of N-α-methylbenzyl benzamides gives configurationally stable tertiary benzyllithiums which undergo a stereospecific dearomatizing cyclization with >99% retention of stereochemistry. The products are partially saturated isoindolinones which carry a new fully-substituted stereogenic centre. A ten-step sequence converts one of these products to the α-methyl analogue of kainic acid.
- Clayden, Jonathan,Knowles, Faye E.,Menet, Christel J.
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p. 3397 - 3400
(2007/10/03)
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- The asymmetric synthesis of β-haloaryl-β-amino acid derivatives
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Lithium N-benzyl-N-α-methyl-4-methoxybenzylamide is employed as a homochiral ammonia equivalent for the asymmetric synthesis of β-haloaryl-β-amino acid derivatives using a conjugate addition/oxidative deprotection strategy.
- Bull,Davies,Delgado-Ballester,Fenton,Kelly,Smith
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p. 1257 - 1260
(2007/10/03)
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- Catalytic asymmetric hydroboration/amination and alkylamination with rhodium complexes of 1,1′-(2-diarylphosphino-1-naphthyl)isoquinoline
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Catecholboronate esters formed by asymmetric hydroboration of arylalkenes are not directly converted to amines by reaction with hydroxylamine-O-sulfonic acid. Prior conversion to a trialkylborane by reaction with ZnEt2 or MeMgCl permits a subsequent amination reaction to occur with essentially complete retention of configuration, leading to a range of primary α-arylalkylamines in up to 97% enantiomeric excess (ee). Secondary, but not tertiary amines may be formed by a related pathway when in situ generated alkylchloramines are employed as the aminating agent. The catalytic asymmetric hydroboration, β-alkylation and amination steps may be combined in a single stage. Overall, this provides a practical procedure for the synthesis of enantiomerically enriched arylamines, exemplified inter alia by the synthesis of (S)-1,2,3,4-tetrahydro-1-naphthylamine in 95-97% ee and of (R)-N-(cyclohexyl)-1′-(4-methoxyphenyl)ethylamine in 93 % ee.
- Fernandez, Elena,Maeda, Kenji,Hooper, Mark W.,Brown, John M.
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p. 1840 - 1846
(2007/10/03)
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- Heterogenised iridium complexes for the asymmetric hydrogenation of imines
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A method for immobilising preformed chiral homogeneous catalysts to a clay support material has been developed. The observed asymmetric induction in the hydrogenation of imines with the supported species was greater than that with the corresponding homoge
- Margalef-Catala, Ramon,Claver, Carmen,Salagre, Pilar,Fernandez, Elena
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p. 1469 - 1476
(2007/10/03)
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- Catalytic asymmetric hydrogenation of imines with a chiral titanocene catalyst: Scope and limitations
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The asymmetric hydrogenation of imines with a chiral titanocene catalyst derived from Brintzinger's ansatitanocene complex 1 proceeds to afford amines with good to excellent enantioselectivity. The catalyst is particularly effective for the reduction of cyclic imines. For these substrates enantiomeric excesses from 95 to 99% were achieved. For acyclic imines lower enantiomeric excesses were observed. The reason for this is likely due to the fact that the acyclic imines are mixtures of anti and syn isomers which interconvert during the reaction. The catalyst was found to be tolerant of many functional groups found in organic synthesis. Thus the reaction represents an effective method for the synthesis of chiral cyclic amines.
- Willoughby, Christopher A.,Buchwald, Stephen L.
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p. 8952 - 8965
(2007/10/02)
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- IMPROVING ENANTIOSELECTIVITY BY USING A MONO-SULPHONATED DIPHOSPHINE AS LIGAND FOR HOMOGENOUS IMINE HYDROGENATION
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The Rhodium catalysed hydrogenation of acetophenone N-benzylimine using mono-sulphonated (2S,4S)-bis-(diphenylphosphino)pentane as ligand gives the corresponding amine with 94percent e.e., whereas use of the di-sulphonated ligand yields product with 2percent e.e.
- Lensink, Cornelis,Vries, Johannes G. de
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p. 235 - 238
(2007/10/02)
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- Rhodium(I)-Sulfonated-bdpp Catalysed Asymmetric Hydrogenation of Imines in Aqueous-Organic Two-phase Solvent Systems
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The imines ArC(Me)=NCH2Ph (Ar = Ph, 2-MeO-C6H4, 3-MeO-C6H4, 4-MeO-C6H4) are hydrogenated to the corresponding amines with extremely high enantioselectivities up to 96percent under very mild conditions, using rhodium complexes associated with sulfonated bdpp.
- Bakos, Jozsef,Orosz, Arpad,Heil, Balint,Laghmari, Mohamed,Lhoste, Paul,Sinou, Denis
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p. 1684 - 1685
(2007/10/02)
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- Rhodium(I)-catalysed Asymmetric Hydrogenation of Imines
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The imines ArC(Me)=NCH2Ph (Ar = Ph, 2-MeO-C6H4, 4-MeO-C6H4) are hydrogenated to the corresponding secondary amines at 1000 psig H2, in 1:1 C6H6/MeOH, using an in situ RhI/(R)-cycphos system (cycphos = Ph2PCH(C6H11)CH2PPh2); a maximum of 91percent enantiomeric excess (e.e.) is achieved at lower temperatures (-25 deg C) in the presence of iodide cocatalyst.
- Kang, Guo-Jun,Cullen, William R.,Fryzuk, Michael D.,James, Brian R.,Kutney, James P.
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p. 1466 - 1467
(2007/10/02)
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