- Highly enantioselective hydrogenation of quinolines under solvent-free or highly concentrated conditions
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The phosphine-free chiral cationic Ru(OTf)(TsDPEN)(η6- cymene) complex was found to be an efficient catalyst for the enantioselective hydrogenation of quinolines under more environmentally friendly solvent-free or highly concentrated conditions
- Wang, Zhi-Jian,Zhou, Hai-Feng,Wang, Tian-Li,He, Yan-Mei,Fan, Qing-Hua
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Read Online
- N-Phthaloyl-(S)-alanyl chloride as a chiral resolving agent for the kinetic resolution of heterocyclic amines
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Acylation of heterocyclic amines with N-phthaloyl-(S)-alanyl chloride under kinetic resolution conditions resulted in the predominant formation of (S,S)-amides. The diastereoselectivity of resolution depended heavily on the structure of the resolved amine.
- Krasnov, Victor P.,Levit, Galina L.,Kodess, Mikhail I.,Charushin, Valery N.,Chupakhin, Oleg N.
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Read Online
- DUAL KINASE-BROMODOMAIN INHIBITORS
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Provided herein are compounds of Formula (I) that are dual inhibitors of kinases and bromo-domain proteins. The disclosure also relates to pharmaceutical compositions containing such compounds, methods for using such compounds in the treatment of cancers, particularly, the treatment of multiple myeloma cancers, and to related uses.
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Page/Page column 92; 124
(2021/12/12)
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- Manganese-Catalyzed Asymmetric Hydrogenation of Quinolines Enabled by π–π Interaction**
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The non-noble metal-catalyzed asymmetric hydrogenation of N-heteroaromatics, quinolines, is reported. A new chiral pincer manganese catalyst showed outstanding catalytic activity in the asymmetric hydrogenation of quinolines, affording high yields and enantioselectivities (up to 97 % ee). A turnover number of 3840 was reached at a low catalyst loading (S/C=4000), which is competitive with the activity of most effective noble metal catalysts for this reaction. The precise regulation of the enantioselectivity were ensured by a π–π interaction.
- Liu, Chenguang,Wang, Mingyang,Liu, Shihan,Wang, Yujie,Peng, Yong,Lan, Yu,Liu, Qiang
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supporting information
p. 5108 - 5113
(2021/01/21)
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- Alternative Strategy to Obtain Artificial Imine Reductase by Exploiting Vancomycin/D-Ala-D-Ala Interactions with an Iridium Metal Complex
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Based on the supramolecular interaction between vancomycin (Van), an antibiotic glycopeptide, and D-Ala-D-Ala (DADA) dipeptides, a novel class of artificial metalloenzymes was synthesized and characterized. The presence of an iridium(III) ligand at the N-terminus of DADA allowed the use of the metalloenzyme as a catalyst in the asymmetric transfer hydrogenation of cyclic imines. In particular, the type of link between DADA and the metal-chelating moiety was found to be fundamental for inducing asymmetry in the reaction outcome, as highlighted by both computational studies and catalytic results. Using the [IrCp*(m-I)Cl]Cl Van complex in 0.1 M CH3COONa buffer at pH 5, a significant 70% (S) e.e. was obtained in the reduction of quinaldine B.
- Facchetti, Giorgio,Bucci, Raffaella,Fusè, Marco,Erba, Emanuela,Gandolfi, Raffaella,Pellegrino, Sara,Rimoldi, Isabella
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p. 2976 - 2982
(2021/03/01)
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- Enantiodivergent Synthesis of Chiral Tetrahydroquinoline Derivatives via Ir-Catalyzed Asymmetric Hydrogenation: Solvent-Dependent Enantioselective Control and Mechanistic Investigations
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Ir-catalyzed asymmetric hydrogenation of quinolines was developed, and both enantiomers of chiral tetrahydroquinoline derivatives could be easily obtained, respectively, in high yields with good enantioselectivities through the adjustment of reaction solvents (toluene/dioxane: up to 99% yield, 98% ee (R), TON = 680; EtOH: up to 99% yield, 94% ee (S), TON = 1680). It provided an efficient and simple synthetic strategy for the enantiodivergent synthesis of chiral tetrahydroquinolines, and gram-scale asymmetric hydrogenation proceeded well with low-catalyst loading in these two reaction systems. A series of deuterium-labeling experiments, control experiments, and 1H NMR and electrospray ionization-mass spectrometry experiments have been conducted, and a reasonable and possible reaction process was revealed on the basis of these useful observations.
- Han, Zhengyu,Liu, Gang,Yang, Xuanliang,Dong, Xiu-Qin,Zhang, Xumu
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p. 7281 - 7291
(2021/06/30)
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- Low-Temperature Nickel-Catalyzed C?N Cross-Coupling via Kinetic Resolution Enabled by a Bulky and Flexible Chiral N-Heterocyclic Carbene Ligand
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The transition-metal-catalyzed C?N cross-coupling has revolutionized the construction of amines. Despite the innovations of multiple generations of ligands to modulate the reactivity of the metal center, ligands for the low-temperature enantioselective amination of aryl halides remain a coveted target of catalyst engineering. Designs that promote one elementary reaction often create bottlenecks at other steps. We here report an unprecedented low-temperature (as low as ?50 °C), enantioselective Ni-catalyzed C?N cross-coupling of aryl chlorides with sterically hindered secondary amines via a kinetic resolution process (s factor up to >300). A bulky yet flexible chiral N-heterocyclic carbene (NHC) ligand is leveraged to drive both oxidative addition and reductive elimination with low barriers and control the enantioselectivity. Computational studies indicate that the rotations of multiple σ-bonds on the C2-symmetric chiral ligand adapt to the changing needs of catalytic processes. We expect this design would be widely applicable to diverse transition states to achieve other challenging metal-catalyzed asymmetric cross-coupling reactions.
- Hong, Xin,Shi, Shi-Liang,Wang, Zi-Chao,Xie, Pei-Pei,Xu, Youjun
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supporting information
p. 16077 - 16084
(2021/06/17)
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- Enantioselective Synthesis of Tetrahydroquinolines via One-Pot Cascade Biomimetic Reduction?
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A novel and efficient protocol for the synthesis of chiral tetrahydroquinoline derivatives with excellent enantioselectivities and high yields has been developed through one-pot cascade biomimetic reduction. The detailed reaction pathway includes the acid-catalyzed and ruthenium-catalyzed formation of aromatic quinoline intermediates and biomimetic asymmetric reduction.
- Zhao, Zi-Biao,Li, Xiang,Chen, Mu-Wang,Wu, Bo,Zhou, Yong-Gui
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supporting information
p. 1691 - 1695
(2020/11/03)
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- Efficient Asymmetric Hydrogenation of Quinolines over Chiral Porous Polymers Integrated with Substrate Activation Sites
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Heterogeneous asymmetric hydrogenation of quinolines for the production of optically active tetrahydroquinoline derivatives still remains a difficult task due to the aromatic stability of quinolines. Herein, we reported efficient heterogeneous asymmetric hydrogenation of quinolines over chiral porous polymers integrated with both chiral active sites (VDPEN-RuOTs) and substrate activation sites (TsOH). The porous polymer integrated with TsOH is 10 times more active than that without TsOH in the asymmetric hydrogenation of 2-methylquinoline. The volcano curve of TOF with the TsOH/Ru ratio confirms the synergistic catalysis of VDPEN-RuOTs and TsOH. Comparison results with a homogeneous catalytic system imply that the synergy between chiral centers and acidic sites is greatly enhanced in the polymer network. Under optimized conditions, the chiral porous polymer afforded up to 90% ee with 90 h-1 TOF, which is one of the best solid catalysts for asymmetric hydrogenation of quinoline derivatives ever reported. Furthermore, the bifunctional porous polymers realized the asymmetric cascade hydrogenation/reductive amination reaction to obtain benzo-quinolizidines. Our primary results suggest that the incorporation of substrate activation sites near chiral centers is an efficient strategy for the synthesis of high-performance solid catalysts for heterogeneous asymmetric catalysis.
- Chen, Xuelian,Li, Chunzhi,Li, He,Liu, Lina,Ren, Yiqi,Tao, Lin,Yang, Qihua
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p. 1783 - 1791
(2020/01/31)
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- Exploration of chiral diastereomeric spiroketal (SPIROL)-based phosphinite ligands in asymmetric hydrogenation of heterocycles
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New and readily available chiral SPIROL-based diphosphinite ligands (SPIRAPO) have been prepared and employed for iridium-catalyzed asymmetric hydrogenations of quinolines, quinoxalines and 2H-1,4-bezoxazin-2-ones. While the structurally similar (R,R,R)-SPIRAPO and (R)-SPINOL-based phosphinites were not the best ligands for these transformations, the (S,R,R)-diastereomer of SPIRAPO was found to be highly effective ligand for the reduction of 20 different heterocyclic systems with loadings as low as S/C = 10?000. This dearomatizative hydrogenation provided direct access to optically active tetrahydroquinolines in high enantioselectivities (up to 94percent ee) and excellent yields (up to 99percent), and was used to generate 1.75 g of natural alkaloid (-)-(R)-angustureine. This protocol was subsequently extended to achieve asymmetric hydrogenation of quinoxalines and 2H-1,4-benzoxazin-2-ones in good to excellent enantioselectivities.
- Sun, Siyuan,Nagorny, Pavel
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supporting information
p. 8432 - 8435
(2020/08/13)
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- (S)-(?)-Fluorenylethylchloroformate (FLEC); preparation using asymmetric transfer hydrogenation and application to the analysis and resolution of amines
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Fluorenylethylchoroformate (FLEC) is a valuable chiral derivatisation reagent that is used for the resolution of a wide variety of chiral amines. Herein, we describe an improved preparation of (S)-(?)-FLEC using an efficient asymmetric catalytic transfer hydrogenation as the key step. We also demonstrate the application of FLEC as a chiral Fmoc equivalent for chiral resolution, with facile deprotection, of tetrahydroquinaldines, and its capacity for inducing regioselective outcomes in nitration reactions.
- Amin, Mohammad A.,Camerino, Michelle A.,Mountford, Simon J.,Ma, Xiao,Manallack, David T.,Chalmers, David K.,Wills, Martin,Thompson, Philip E.
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- Visible-Light Induction/Br?nsted Acid Catalysis in Relay for the Enantioselective Synthesis of Tetrahydroquinolines
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An efficient method merging Br?nsted acid catalysis with visible-light induction for the highly enantioselective synthesis of tetrahydroquinolines has been developed. This mild process directly transforms 2-aminoenones into 2-substituted tetrahydroquinolines with excellent enantioselectivities through a relay visible-light-induced cyclization/chiral phosphoric acid-catalyzed transfer hydrogenation reaction.
- Xiong, Wenhui,Li, Shan,Fu, Bo,Wang, Jinping,Wang, Qiu-An,Yang, Wen
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p. 4173 - 4176
(2019/06/07)
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- Breaking Symmetry: Engineering Single-Chain Dimeric Streptavidin as Host for Artificial Metalloenzymes
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The biotin-streptavidin technology has been extensively exploited to engineer artificial metalloenzymes (ArMs) that catalyze a dozen different reactions. Despite its versatility, the homotetrameric nature of streptavidin (Sav) and the noncooperative binding of biotinylated cofactors impose two limitations on the genetic optimization of ArMs: (i) point mutations are reflected in all four subunits of Sav, and (ii) the noncooperative binding of biotinylated cofactors to Sav may lead to an erosion in the catalytic performance, depending on the cofactor:biotin-binding site ratio. To address these challenges, we report on our efforts to engineer a (monovalent) single-chain dimeric streptavidin (scdSav) as scaffold for Sav-based ArMs. The versatility of scdSav as host protein is highlighted for the asymmetric transfer hydrogenation of prochiral imines using [Cp*Ir(biot-p-L)Cl] as cofactor. By capitalizing on a more precise genetic fine-tuning of the biotin-binding vestibule, unrivaled levels of activity and selectivity were achieved for the reduction of challenging prochiral imines. Comparison of the saturation kinetic data and X-ray structures of [Cp*Ir(biot-p-L)Cl]·scdSav with a structurally related [Cp*Ir(biot-p-L)Cl]·monovalent scdSav highlights the advantages of the presence of a single biotinylated cofactor precisely localized within the biotin-binding vestibule of the monovalent scdSav. The practicality of scdSav-based ArMs was illustrated for the reduction of the salsolidine precursor (500 mM) to afford (R)-salsolidine in 90% ee and >17 ?000 TONs. Monovalent scdSav thus provides a versatile scaffold to evolve more efficient ArMs for in vivo catalysis and large-scale applications.
- Wu, Shuke,Zhou, Yi,Rebelein, Johannes G.,Kuhn, Miriam,Mallin, Hendrik,Zhao, Jingming,Igareta, Nico V.,Ward, Thomas R.
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supporting information
p. 15869 - 15878
(2019/10/11)
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- Axial-chirality bidentate ligand and application thereof in palladium-catalyzed asymmetric hydrogen transfer reaction
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The invention discloses an axial-chirality bidentate ligand and application thereof in a palladium-catalyzed asymmetric hydrogen transfer reaction. The structural formula of the axial-chirality bidentate ligand is shown in the original specification, wherein R is H, 2, 4, 6-Me, 2, 4, 6-t-Bu and 2, 4, 6-F. The application of the axial-chirality bidentate ligand in the palladium-catalyzed asymmetrichydrogen transfer reaction comprises the following steps: stirring the axial-chirality bidentate ligand and palladium salt in diethyl ether for coordination, concentrating and performing spin drying,so as to obtain a catalyst; adding quinoline into a 10mL single aperture reaction flask, adding chloroform into the reaction flask for dissolving by taking Hantzsch ester, adding 0.01-0.05mol% of thecatalyst into the reaction flask, performing a reaction at room temperature for 6-12h and directly performing column chromatography after the reaction is ended, so as to obtain a target product. According to the axial-chirality bidentate ligand and the application thereof in the palladium-catalyzed asymmetric hydrogen transfer reaction, the technical problem that how the relatively high yield isobtained under a mild condition can be solved.
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Paragraph 0014; 0015; 0016; 0017; 0018; 0019
(2019/02/27)
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- Spiro-Bicyclic Bisborane Catalysts for Metal-Free Chemoselective and Enantioselective Hydrogenation of Quinolines
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A new series of spiro-bicyclic bisborane catalysts has been prepared by means of hydroboration reactions of C2-symmetric spiro-bicyclic dienes with HB(C6F5)2 and HB(p-C6F4H)2. When used for hydrogenation of quinolines, these catalysts give excellent yields and enantiomeric excesses, and show turnover numbers of up to 460. The most attractive feature of these metal-free hydrogenation reactions was the broad functional-group tolerance, making this method complementary to existing methods for quinoline hydrogenation.
- Li, Xiang,Tian, Jun-Jie,Liu, Ning,Tu, Xian-Shuang,Zeng, Ning-Ning,Wang, Xiao-Chen
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supporting information
p. 4664 - 4668
(2019/03/26)
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- P -Chiral, N -phosphoryl sulfonamide Br?nsted acids with an intramolecular hydrogen bond interaction that modulates organocatalysis
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Br?nsted acids exemplified by OttoPhosa I (5c) were designed and evaluated in the asymmetric transfer hydrogenation of quinolines. Their catalytic properties are modulated by an intramolecular hydrogen bond that rigidifies their catalytic cavity, accelerates the reaction rate and improves enantioselectivity.
- Yuan, Minglei,Mbaezue, Ifenna I.,Zhou, Zhi,Topic, Filip,Tsantrizos, Youla S.
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supporting information
p. 8690 - 8694
(2019/10/16)
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- DIRECT C-H AMINATION AND AZA-ANNULATION
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In some aspects, the present disclosure provides methods of aminating an aromatic compound comprising reacting an aminating agent with an aromatic compound in the presence of a rhodium catalyst. In some embodiments, the methods may comprise aminating an aromatic compound which contains multiple different functional groups. The methods described herein may also be used to create bicyclic system comprising reacting an intramolecular aminating agent with an aromatic ring to obtain a second ring containing a nitrogen atom. In another aspect, the methods described herein may also be used to create a cyclic aliphatic cyclic/poly cyclic amine system comprising a reacting an intramolecular aminating agent by insertion into a C(sp3)-H bond.
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Paragraph 0132; 0224
(2019/06/07)
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- Diastereoselective Acylation of Racemic Heterocyclic Amines with N-Phthaloyl and N-Naphthaloyl (S)-Amino Acyl Chlorides: Possibility of Parallel Kinetic Resolution
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Abstract: The acylative kinetic resolution of racemic 2-methyl-1,2,3,4-tetrahydroquinoline and 3,4-dihydro-3-methyl-2H-[1,4]benzoxazines with acyl chlorides of N-naphthaloyl-(S)-alanine and N-naphthaloyl-(S)-phenylalanine has been studied. It has been shown that diastereoselective acylation of racemic amines with N-naphthaloyl (S)-amino acyl chlorides results in the predominant formation of (R,S)-amides, whereas acylation of the same amines with N-phthaloyl (S)-amino acyl chlorides proceeds with the opposite diastereoselectivity. The parallel kinetic resolution of racemic 3,4-dihydro-3-methyl-2H-[1,4]benzoxazine using a mixture of acylating agents derived from a single precursor, (S)-phenylalanine, was carried out.
- Gruzdev,Chulakov,Sadretdinova, L. Sh.,Levit,Krasnov,Charushin
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p. 293 - 296
(2019/02/05)
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- A one-pot process for the enantioselective synthesis of tetrahydroquinolines and tetrahydroisoquinolines: Via asymmetric reductive amination (ARA)
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Asymmetric reductive amination for the synthesis of both chiral tetrahydroquinolines (THQs) and tetrahydroisoquinolines (THIQs) has been realized with an Ir/ZhaoPhos catalytic system via a one-pot N-Boc deprotection/intramolecular asymmetric reductive amination (ARA) sequence. Control experiments reveal that HCl plays a vital role to the success of this transformation. The HCl acid assists the removal of the N-Boc protecting group and also provides chloride ions to interact with the thiourea moiety in ZhaoPhos, thus leading to excellent reaction enantiocontrol.
- Yang, Tao,Yin, Qin,Gu, Guoxian,Zhang, Xumu
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p. 7247 - 7250
(2018/07/05)
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- Cyclopentadiene-based Br?nsted acid as a new generation of organocatalyst for transfer hydrogenation of 2-substituted quinoline derivatives
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A simple and readily available cyclopentadiene-based Br?nsted acid was employed to catalyze the transfer hydrogenation of 2-substituted quinolines using Hantzsch ester as the hydrogen source. This conceptually new designed organocatalyst demonstrates remarkably high efficiency for this transformation and a variety of substituted 1,2,3,4-tetrahydroquinoline derivatives were afforded in excellent yields under mild reaction conditions.
- Qiao, Xiang,El-Shahat, Mahmoud,Ullah, Bakhtar,Bao, Zongbi,Xing, Huabin,Xiao, Li,Ren, Qilong,Zhang, Zhiguo
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p. 2050 - 2053
(2017/05/04)
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- Enantioselective Reduction of 3-Substituted Quinolines with a Cyclopentadiene-Based Chiral Br?nsted Acid
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Enantioselective reduction of 3-substituted quinolines has been achieved using a cyclopentadiene-based chiral Bronsted acid as catalyst and Hantzsch ester as hydrogen donor, affording the corresponding tetrahydroquinolines in good enantioselectivities.
- Zhao, Xiaofang,Xiao, Jianliang,Tang, Weijun
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supporting information
p. 3157 - 3164
(2017/07/12)
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- IRIDIUM COMPLEX
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PROBLEM TO BE SOLVED: To provide an iridium complex applicable for an industrial catalyst reaction. SOLUTION: The present invention provides an iridium complex represented by the following formula [I]. In the presence of the iridium complex, a hydrogen donative compound and an imine react with each other, so that an amine can be produced. SELECTED DRAWING: None COPYRIGHT: (C)2017,JPOandINPIT
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Paragraph 0090-0091
(2017/08/18)
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- B(C6F5)3-Promoted hydrogenations of N-heterocycles with ammonia borane
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A transition-metal-free method for the B(C6F5)3-promoted hydrogenations of N-heterocycles using ammonia borane under mild reaction conditions has been developed. The reaction affords a broad range of hydrogenated products in moderate to good yields. The enantioselective versions for the corresponding products were also investigated via our approach, showing good feasibility.
- Ding, Fangwei,Zhang, Yiliang,Zhao, Rong,Jiang, Yanqiu,Bao, Robert Li-Yuan,Lin, Kaifeng,Shi, Lei
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supporting information
p. 9262 - 9264
(2017/08/21)
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- Enantioselective hydrogenation of N-heteroaromatics catalyzed by chiral diphosphine modified binaphthyl palladium nanoparticles
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The first application of binaphthyl-stabilized palladium nanoparticles (Bin-PdNPs) with chiral modifiers in asymmetric hydrogenation of N-heteroaromatics is revealed. With an appropriate ratio of R-BINAP/Bin-PdNPs used, the pre-prepared chiral nanocatalyst achieves asymmetric hydrogenations of 2-substituted quinolines with good to excellent yields and moderate enantioselectivities, which showed superior catalytic properties to the R-BINAP/Pd complex. Moreover, this protocol is also applicable to 2-substituted indoles.
- Xia, Yun-Tao,Ma, Jing,Wang, Xiao-Dong,Yang, Lei,Wu, Lei
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p. 5515 - 5520
(2017/12/07)
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- Origin of the chemical stability of phosphine-phosphoramidites: Structural study of an UPPhostype crystal and application of UPPhos in the asymmetric hydrogenation of imines
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Phosphine-phosphoramidites (PPAs) are heterobidentate ligands that have been developed in the last two decades and have been used successfully in asymmetric catalytic reactions. A single crystal of the PPA (11bS)-N-[(2S,4S)-4-(diphenylphosphanyl)pentan-2-yl]-N-methyldinaphtho[2,1-d:1′,2′-f][1,3,2]dioxaphosphepin-4-amine, C38H35NO2P2, was prepared and structurally characterized by single-crystal X-ray diffraction and density functional theory (DFT) calculations. Structure elucidation revealed unique features which might have a significant effect in the excellent chemical stability of this type of molecule. The conformation of the molecule provides an optimal chelating structure. Iridium complexes of UPPhos were found to be efficient catalysts in the asymmetric hydrogenation of imines {UPPhos is (11bS)-N-[(2S,4S)-4-(diphenylphosphanyl)pentan-2-yl]-N-(propan-2-yl)dinaphtho[2,1-d:1′,2′-f][1,3,2]dioxaphosphepin-4-amine}.
- Balogh, Szabolcs,Farkas, Gergely,Holczbauer, Tamás,Bakos, József
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p. 632 - 637
(2017/08/09)
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- Application of Off-Rate Screening in the Identification of Novel Pan-Isoform Inhibitors of Pyruvate Dehydrogenase Kinase
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Libraries of nonpurified resorcinol amide derivatives were screened by surface plasmon resonance (SPR) to determine the binding dissociation constant (off-rate, kd) for compounds binding to the pyruvate dehydrogenase kinase (PDHK) enzyme. Parallel off-rate measurements against HSP90 and application of structure-based drug design enabled rapid hit to lead progression in a program to identify pan-isoform ATP-competitive inhibitors of PDHK. Lead optimization identified selective sub-100-nM inhibitors of the enzyme which significantly reduced phosphorylation of the E1α subunit in the PC3 cancer cell line in vitro.
- Brough, Paul A.,Baker, Lisa,Bedford, Simon,Brown, Kirsten,Chavda, Seema,Chell, Victoria,D’Alessandro, Jalanie,Davies, Nicholas G. M.,Davis, Ben,Le Strat, Loic,Macias, Alba T.,Maddox, Daniel,Mahon, Patrick C.,Massey, Andrew J.,Matassova, Natalia,McKenna, Sean,Meissner, Johannes W. G.,Moore, Jonathan D.,Murray, James B.,Northfield, Christopher J.,Parry, Charles,Parsons, Rachel,Roughley, Stephen D.,Shaw, Terry,Simmonite, Heather,Stokes, Stephen,Surgenor, Allan,Stefaniak, Emma,Robertson, Alan,Wang, Yikang,Webb, Paul,Whitehead, Neil,Wood, Mike
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p. 2271 - 2286
(2017/04/03)
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- Strong Br?nsted acid promoted asymmetric hydrogenation of isoquinolines and quinolines catalyzed by a Rh-thiourea chiral phosphine complex: Via anion binding
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Rhodium catalyzed asymmetric hydrogenation of both isoquinolines and quinolines provides a new method to synthesize chiral tetrahydroisoquinolines and tetrahydroquinolines. By introducing strong Br?nsted acid HCl, anion binding between the substrate and t
- Wen, Jialin,Tan, Renchang,Liu, Shaodong,Zhao, Qingyang,Zhang, Xumu
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p. 3047 - 3051
(2016/05/19)
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- Acylative kinetic resolution of racemic heterocyclic amines with (R)-2-phenoxypropionyl chloride
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The acylative kinetic resolution of racemic heterocyclic amines such as 3,4-dihydro-3-methyl-2H-[1,4]benzoxazines, 3,4-dihydro-3-methyl-2H-[1,4]benzothiazine, 2-methyl-1,2,3,4-tetrahydro-quinolines and 2-methylindoline with enantiopure (R)-2-phenoxypropionyl chloride has been studied. It has been found that acylation of 3,4-dihydro-3-methyl-2H-[1,4]benzothiazine proceeds with the best stereoselectively when compared with other racemic amines. An efficient method for the preparation of (S)-3,4-dihydro-3-methyl-2H-[1,4]benzothiazine (99.4% ee) via a kinetic resolution protocol was developed. The possibility of recycling (R)-2-phenoxypropionic acid has been demonstrated.
- Vakarov, Sergey A.,Gruzdev, Dmitry A.,Chulakov, Evgeny N.,Sadretdinova, Liliya Sh.,Tumashov, Andrey A.,Pervova, Marina G.,Ezhikova, Marina A.,Kodess, Mikhail I.,Levit, Galina L.,Krasnov, Victor P.,Charushin, Valery N.
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supporting information
p. 1231 - 1237
(2016/11/23)
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- Bio-mediated oxidative resolution of racemic 2-substituted 1,2,3,4-tetrahydroquinolines
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Whole cell of Pseudomonas monteilii ZMU-T01 strains mediated oxidative resolution of racemic 2-substituted 1,2,3,4-tetrahydroquinolines has been successfully described. A series of highly enantioselective 2-substituted 1,2,3,4-tetrahydroquinoline derivatives were obtained in up to 50% conversion and >99% ee.
- Qin, Lei,Zheng, Daijun,Cui, Baodong,Wan, Nanwei,Zhou, Xiaojian,Chen, Yongzheng
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supporting information
p. 2403 - 2405
(2016/05/19)
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- Iridium-Catalyzed Transfer Hydrogenation of 1,10-Phenanthrolines using Formic Acid as the Hydrogen Source
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The iridium-catalyzed highly regioselective transfer hydrogenation of a variety of 2-substituted and 2,9-disubstituted 1,10-phenanthrolines under mild conditions with formic acid as the hydrogen source is described. In the presence of a catalytic amount of the iridium complex [CpIrCl2]2, the transfer hydrogenation proceeded smoothly in 1,4-dioxane under ligand-free conditions, exclusively leading to a range of 1,2,3,4-tetrahydro-1,10-phenanthroline products in high yields. The catalyst generated in situ from [CpIrCl2]2 and (R,R)-(CF3)2C6H3SO2-dpen [N-(2-amino-1,2-diphenylethyl)-3,5-bis(trifluoromethyl)benzenesulfonamide] could efficiently catalyze the asymmetric transfer hydrogenation of these 1,10-phenanthrolines in isopropyl alcohol (i-PrOH) to afford chiral 1,2,3,4-tetrahydro-1,10-phenanthrolines in high yields with up to >99% ee. The key to the success of the reduction is the choice of solvent and hydrogen source.
- Xu, Conghui,Zhang, Lingjuan,Dong, Chaonan,Xu, Jianbin,Pan, Yixiao,Li, Yali,Zhang, Hanyu,Li, Huanrong,Yu, Zhiyong,Xu, Lijin
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supporting information
p. 567 - 572
(2016/02/27)
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- Solvent-Regulated Asymmetric Hydrogenation of Quinoline Derivatives in Oligo(Ethylene Glycol)s through Host–Guest Interactions
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The asymmetric hydrogenation of quinolines in oligo(ethylene glycol)s (OEGs) and poly(ethylene glycol)s (PEGs) with chiral cationic ruthenium diamine complexes has been investigated. Interestingly, in liquid PEGs or long-chain OEGs, the Ru catalysts lost their reactivity. Upon the addition of a little MeOH, the hydrogenation of quinoline was switched “ON”. Evidence from mass spectrometry and control experiments revealed that encapsulation of the quinolinium salt by PEG or long-chain OEG molecules through supramolecular interactions is possibly the main reason for such a switchable hydrogenation reaction. Moreover, the asymmetric hydrogenation of 2-substituted quinoline derivatives was achieved in triethylene glycol (3-OEG), thereby affording 1,2,3,4-tetrahydroquinolines with excellent reactivities and enantioselectivities (up to 99 % ee). Furthermore, the Ru catalyst could be readily recycled for both pure 3-OEG and biphasic 3-OEG/n-hexane systems without a clear loss of reactivity and enantioselectivity.
- Wang, Tianli,Chen, Ya,Ouyang, Guanghui,He, Yan-Mei,Li, Zhiyan,Fan, Qing-Hua
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p. 2773 - 2777
(2016/10/11)
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- METHOD FOR PRODUCING OPTICALLY ACTIVE COMPOUND, AND NOVEL METAL-DIAMINE COMPLEX
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The present invention pertains to a method for producing an optically active compound which includes a step for reducing an imino group of an imine compound or a step for reducing an unsaturated bond of a heterocyclic compound, while in the presence of hydrogen gas as a hydrogen donor and one or more types of complexes selected from a group consisting of a complex represented by general formula (1), a complex represented by general formula (2), a complex represented by general formula (3), and a complex represented by general formula (4) (the general formulas (1)-(4) are as stipulated by claim 1).
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Paragraph 0238; 0239
(2016/12/22)
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- Dirhodium-catalyzed C-H arene amination using hydroxylamines
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Primary and N-alkyl arylamine motifs are key functional groups in pharmaceuticals, agrochemicals, and functional materials, as well as in bioactive natural products. However, there is a dearth of generally applicablemethods for the direct replacement of aryl hydrogens with NH2/NH(alkyl) moieties. Here, we present a mild dirhodium-catalyzed C-H amination for conversion of structurally diverse monocyclic and fused aromatics to the corresponding primary and N-alkyl arylamines using NH2/NH(alkyl)-O-(sulfonyl)hydroxylamines as aminating agents; the relatively weak RSO2O-N bond functions as an internal oxidant. The methodology is operationally simple, scalable, and fast at or below ambient temperature, furnishing arylamines in moderate-to-good yields and with good regioselectivity. It can be readily extended to the synthesis of fused N-heterocycles.
- Paudyal, Mahesh P.,Adebesin, Adeniyi Michael,Burt, Scott R.,Ess, Daniel H.,Ma, Zhiwei,Kürti, László,Falck, John R.
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p. 1144 - 1147
(2016/11/09)
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- Conjugated microporous polymers with chiral BINAP ligand built-in as efficient catalysts for asymmetric hydrogenation
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A series of chiral conjugated microporous polymers (CMPs) based on the chiral (R)-BINAP ligand (BINAP-CMPs) were synthesized with tunable BET surface areas. These solid catalysts show high activities and enantioselectivities for the asymmetric hydrogenation of β-keto esters after coordination with ruthenium species. Moreover, CMPs can realize spatial isolation. Through preventing the formation of dimers and trimers, BINAP-CMPs show much higher activity than BINAP for the Ir-catalyzed asymmetric hydrogenation of quinaldine.
- Wang, Xu,Lu, Sheng-Mei,Li, Jun,Liu, Yan,Li, Can
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p. 2585 - 2589
(2015/05/13)
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- P-Stereogenic pincer iridium complexes: Synthesis, structural characterization and application in asymmetric hydrogenation
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P-Stereogenic PNP type pincer iridium complexes PNPtBuMeIrH2Cl (3) and PNPtBuMeIrH3 (4) were synthesized in reasonable yields and characterized by 1H NMR, 13C NMR, 31P NMR, HRMS and/or single crystal X-ray diffraction. The ORTEP diagram shows that the coordination geometry around the iridium center of complex 3 is approximately octahedral. The chlorinated iridium complex (3) and/or the trihydride iridium complex (4) were used as catalysts in the asymmetric hydrogenation of ketones, olefins and quinoline to provide the desired products with up to 17% enantioselectivity.
- Yang, Zehua,Wei, Xuan,Liu, Delong,Liu, Yangang,Sugiya, Masashi,Imamoto, Tsuneo,Zhang, Wanbin
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- Low Pressure Asymmetric Hydrogenation of Quinolines using an Annulated Planar Chiral N-Ferrocenyl NHC-Iridium Complex
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Annulated planar chiral N-ferrocenylimidazolones, obtained by acid-mediated cyclization of diphenylmethanol derivatives, may be reduced with diisobutylaluminium hydide (DIBAL-H) to afford a series of surprisingly stable and isolable hemiaminal ether aminals. Two of these derivatives can be oxidized with triphenylcarbenium tetrafluoroborate to imidazolinium salt precursors of N-heterocyclic carbenes (NHCs). Deprotonation of these salts in the presence of (cyclooctadiene)iridium chloride dimer {[Ir(COD)Cl]2} provides chiral coordination complexes bearing N-ferrocenyl NHCs with unique rigid tetracyclic frameworks. Cationic analogues of these complexes catalyze the asymmetric hydrogenation of 2-substituted quinolines under very mild conditions (1 mol% complex, 1 mol% PPh3, 1-5 atm H2, toluene, 25 C) in appreciable enantioselectivity (up to 90:10 er). The sensitivity of the hydrogenation process to changes in the phosphine additive suggests that an outer-sphere reaction mechanism may be involved, as proposed for a related achiral NHC-Ir complex reported by Crabtree and co-workers.
- John, Joshni,Wilson-Konderka, Cody,Metallinos, Costa
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p. 2071 - 2081
(2015/06/23)
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- Efficient enantioselective hydrogenation of quinolines catalyzed by conjugated microporous polymers with embedded chiral BINAP ligand
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Chiral Ir complexes were successfully used in the asymmetric hydrogenation of olefins, ketones, and quinolines. However, almost all the catalytic systems could not tolerate a high catalyst loading because of the formation of an irreversible iridium dimer and trimer during the reaction. It is expected that higher catalytic activity may be achieved if the Ir-complexes were isolated in space. The development of conjugated microporous polymers (CMPs) gives the opportunity for the spatial separation of the complexes. A series of chiral CMPs based on the chiral (R)-BINAP ligand (BINAP-CMPs) with different surface areas were synthesized. The BINAP ligands were separately distributed in the framework and were three times more active than the homogeneous catalyst (TOF 340 h-1 VS 100 h-1) for the asymmetric hydrogenation of quinolines.
- Wang, Xu,Li, Jun,Lu, Shengmei,Liu, Yan,Li, Can
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p. 1170 - 1174
(2015/09/01)
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- Chiral phosphoric acid catalyzed asymmetric transfer hydrogenation of quinolines in a sustainable solvent
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The use of diethyl carbonate as a sustainable solvent for organocatalytic asymmetric transfer hydrogenations of 2-substituted quinolines using highly efficient chiral phosphoric acid catalysts with Hantzsch esters as a hydrogen source is reported for the first time. The asymmetric transfer hydrogenation reaction in diethyl carbonate provides enantiomerically pure 1,2,3,4-tetrahydroquinolines with high yields and excellent enantioselectivities (up to 99% ee). These results clearly confirm that this green and sustainable solvent is an excellent replacement for organic solvents, which are harmful to the environment, and transition metal based catalysts are not required. The effects of different chiral phosphoric acids, solvents, catalyst loading, temperature effect, and reaction time on the conversion and enantioselectivity of desired product are discussed.
- More, Ganesh V.,Bhanage, Bhalchandra M.
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p. 1174 - 1179
(2015/10/28)
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- TETRAHYDROISOQUINOLINE COMPOUNDS AND THEIR USE AS PYRUVATE DEHYDROGENASE KINASE INHIBITORS
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A compound of formula (I): or a pharmaceutically acceptable salt thereof, wherein: R1 is H, Cl, F, CH3 or CF3; R2 is H, C1-C6 alkyl or optionally substituted heteroaryl or optionally substituted aryl; and R3 is (Alk)n-Rn-(Alk)n-Rn-(Alk)n-X. The compounds are useful as tetrahydroisoquinoline (THQ) compounds, which are suitable for use as PDK inhibitors, for example for inhibition of cancer cell proliferation.
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Page/Page column 57; 58
(2015/04/15)
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- Diastereoselective acylation of racemic heterocyclic amines with N-tosyl-(s)-prolyl chloride and its structural analogs
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A comparative study on the kinetic resolution of racemic amines (2,3-dihydro-4H-1,4-benzoxazine and 1,2,3,4-tetrahydroquinoline derivatives) via diastereoselective acylation with N-tosyl-(S)-prolyl chloride and its structural analogs was performed. The effect of resolving agent structure on the stereoselectivity of heterocyclic amine acylation was examined. The highest stereoselectivity was achieved in the case of acylation with acyl chlorides bearing a conformationally restricted pyrrolidine ring and an aromatic substituent in the protecting group at the nitrogen atom.
- Vakarov,Gruzdev,Chulakov,Sadretdinova,Ezhikova,Kodess,Levit,Krasnov
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p. 838 - 855
(2015/09/28)
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- Diastereoselective acylation of racemic heterocyclic amines with N-tosyl-(S)-prolyl chloride and its structural analogs
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A comparative study on the kinetic resolution of racemic amines (2,3-dihydro-4H-1,4-benzoxazine and 1,2,3,4-tetrahydroquinoline derivatives) via diastereoselective acylation with N-tosyl-(S)-prolyl chloride and its structural analogs was performed. The effect of resolving agent structure on the stereoselectivity of heterocyclic amine acylation was examined. The highest stereoselectivity was achieved in the case of acylation with acyl chlorides bearing a conformationally restricted pyrrolidine ring and an aromatic substituent in the protecting group at the nitrogen atom.
- Vakarov,Gruzdev,Chulakov,Sadretdinova, L. Sh.,Ezhikova,Kodess,Levit,Krasnov
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p. 838 - 855
(2014/11/08)
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- Catalytic enantioselective amination of alcohols by the use of borrowing hydrogen methodology: Cooperative catalysis by iridium and a chiral phosphoric acid
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The catalytic asymmetric reduction of ketimines has been explored extensively for the synthesis of chiral amines, with reductants ranging from Hantzsch esters, silanes, and formic acid to H2 gas. Alternatively, the amination of alcohols by the use of borrowing hydrogen methodology has proven a highly atom economical and green method for the production of amines without an external reductant, as the alcohol substrate serves as the H2 donor. A catalytic enantioselective variant of this process for the synthesis of chiral amines, however, was not known. We have examined various transition- metal complexes supported by chiral ligands known for asymmetriC-Hydrogenation reactions, in combination with chiral Bronsted acids, which proved essential for the formation of the imine intermediate and the transfer-hydrogenation step. Our studies led to an asymmetric amination of alcohols to provide access to a wide range of chiral amines with good to excellent enantioselectivity.
- Zhang, Yao,Lim, Ching-Si,Boon Sim, Derek Sui,Pan, Hui-Jie,Zhao, Yu
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supporting information
p. 1399 - 1403
(2014/03/21)
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- The use of phosphite-type ligands in the Ir-catalyzed asymmetric hydrogenation of heterocyclic compounds
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A series of chiral phosphite-type ligands was tested in asymmetric Ir-catalyzed hydrogenation of quinolines and 2,4,5,6-tetrahydro-1H-pyrazino(3,2, 1-j,k)carbazole. Hydrogenation of quinaldine hydrochloride provided superior enantioselectivity up to 65% ee compared to quinaldine free base. The ligands were tested for the first time in the asymmetric Ir-Ircatalyzed hydrogenation of 2,4,5,6-tetrahydro-1H-pyrazino(3,2,1-j,k)carbazole yielding the antidepressant drug, pirlindole. Chirality 26:56-60, 2013. 2013 Wiley Periodicals, Inc.
- Lyubimov, Sergey E.,Ozolin, Dmitry V.,Ivanov, Pavel Yu,Melman, Artem,Velezheva, Valeriya S.,Davankov, Vadim A.
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- Efficient asymmetric hydrogenation of quinolines in neat water catalyzed by chiral cationic Ru-diamine complexes
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We describe herein highly effective asymmetric hydrogenation of quinolines in undegassed water catalyzed by chiral cationic Ru-diamine complexes for the first time. This facile and green protocol is applicable to the scaled-up synthesis of 6-fluoro-2-methyl-1,2,3,4-tetrahydroquinoline, a key intermediate for the preparation of the antibacterial agent (S)-flumequine, with 98% ee. the Partner Organisations 2014.
- Yang, Zhusheng,Chen, Fei,He, Yan-Mei,Yang, Nianfa,Fan, Qing-Hua
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p. 2887 - 2890
(2014/08/18)
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- METHOD FOR PRODUCING OPTICALLY ACTIVE TETRAHYDROQUINOLINE
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Provided are a novel chiral iridium(III) complex; and a method for producing optically active 2-substituted-1,2,3,4-tetrahydroquinolines from 2-substituted-quinolines with the use of the chiral iridium(III) complex through a more economical and easy production process. The disclosed method for producing optically active 2-substituted-1,2,3,4-tetrahydroquinolines comprises reducing a quinoline compound represented by formula [I]: in the presence of a hydrogen donor compound and an iridium(III) complex having a chiral prolinamide compound as a ligand to give an optically active 2-substituted-1,2,3,4-tetrahydroquinoline represented by formula [II]:
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Paragraph 0114; 0115
(2014/06/11)
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- N-tosyl-(S)-prolyl chloride in kinetic resolution of racemic heterocyclic amines
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The kinetic resolution of racemic heterocyclic amines via acylation with N-tosyl-(S)-prolyl chloride was systematically investigated. It was established that racemic mixtures of aromatic amines could be resolved with high efficiency, while the acylation of 2- and 3-methylpiperidines occurred with low diastereoselectivity. A method for the preparation of enantiomerically pure (3R)-7,8-difluoro-3-methyl-3,4-dihydro-2H-[1,4]benzoxazine was developed.
- Gruzdev,Vakarov,Levit,Krasnov
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p. 1795 - 1807
(2014/05/06)
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- Chiral Ru/Ir bimetallic dendronized polymer catalysts constructed through sequential metal coordination and applied in asymmetric hydrogenation of quinaldine
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A new kind of chiral conjugated copolymer P-2 with (S)-BINAP [BINAP = 2,2′-bis(diarylphosphino)-1,1′-binaphthyl] and fluorene as the building blocks was synthesized involving Pd[P(p-tolyl)3] 3-catalyzed Suzuki-coupling reaction together with reduction of phosphine oxide with HSiCl3/NEt3. The chiral polymer was used to construct chiral Ru/Ir bimetallic dendronized polymer catalysts P-5-m with different generations of Fréchet-type dendritic DPEN [DPEN = 1,2-diphenylethylenediamine] ligands through a programmed metal-ligand coordination strategy. These dendronized polymer catalysts were applied to the Ir-catalyzed asymmetric hydrogenation of quinaldine and exhibited excellent activity with moderate enantioselectivity. The reaction rate was increased with increasing generation of the dendronized polymer catalysts, which are better than that obtained from the monomeric catalyst. This interesting positive dendrimer effect might be due to effective shielding of the catalytically active iridium center by the bulky dendritic pendants, which reduced the formation of the inactive iridium dimer.
- Huang, Yi-Yong,Yang, Xing,Feng, Yu,Verpoort, Francis,Fan, Qing-Hua
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p. 150 - 155
(2014/07/21)
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- A comparative study on the acylative kinetic resolution of racemic fluorinated and non-fluorinated 2-methyl-1,2,3,4-tetrahydroquinolines and 3,4-dihydro-3-methyl-2H-[1,4]benzoxazines
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The acylative kinetic resolution of racemic 6-fluoro-2-methyl-1,2,3,4- tetrahydroquinoline, 7,8-difluoro-3,4-dihydro-3-methyl-2H-[1,4]benzoxazine, and their non-fluorinated analogues with (S)-naproxen and N-phthaloyl-(S)-amino acyl chlorides has been carried out. It has been shown that the presence of fluorine atoms in the aromatic fragment of a heterocyclic amine results in the increasing stereoselectivity of acylation with (S)-naproxen acyl chloride and in a decrease in the efficiency of acylative kinetic resolution using N-phthaloyl-(S)-amino acyl chlorides. A method for the preparation of enantiopure (S)-6-fluoro-2-methyl-1,2,3,4-tetrahydroquinoline (ee >99%) was developed.
- Gruzdev, Dmitry A.,Chulakov, Evgeny N.,Levit, Galina L.,Ezhikova, Marina A.,Kodess, Mikhail I.,Krasnov, Victor P.
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p. 1240 - 1246
(2013/10/22)
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- Shedding light on Bronsted acid catalysis-a photocyclization- reduction reaction for the asymmetric synthesis of tetrahydroquinolines from aminochalcones in batch and flow
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A new asymmetric photocyclization-reduction cascade employing readily available aminochalcones has been developed. The reaction sequence has been achieved by unifying photochemistry and asymmetric Bronsted acid catalysis and involves photocyclization followed by Bronsted acid catalyzed enantioselective hydrogenation in batch and flow.
- Liao, Hsuan-Hung,Hsiao, Chien-Chi,Sugiono, Erli,Rueping, Magnus
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supporting information
p. 7953 - 7955
(2013/09/02)
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- Iridium and rhodium complexes with the planar chiral thioether ligands in asymmetric hydrogenation of ketones and imines
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Rhodium complexes with the planar chiral phosphinoferrocenyl thioether ligands [Rh(P,SR)(diene)X] (R = Me, But, Ph, Bn, diene is cyclooctadiene (COD) or norbornadiene (NBD), X = Cl, BF4) catalyze hydrogenation of ketones, imines, and heteroaromatic compounds; in the case of acetophenone, the enantioselectivity reached 60% ee. Similar iridium complexes demonstrate a good activity in the hydrogenation of imines, the maximal enantioselectivity in the case of N-phenyl-N-(1-phenylethylidene)amine was about 40% ee.
- Kozinets,Silantyev,Belkova,Shubina,Poli,Manoury
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p. 751 - 757
(2014/01/23)
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- Highly enantioselective synthesis of chiral tetrahydroquinolines and tetrahydroisoquinolines by ruthenium-catalyzed asymmetric hydrogenation in ionic liquid
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Asymmetric hydrogenation reactions of quinolines and 3,4- dihydroisoquinolines using the chiral cationic ruthenium complex Ru(TsDPEN) [TsDPEN=N-(p-toluenesulfonyl)-1,2-diphenylethylenediamine] as catalyst in neat imidazolium ionic liquids have been investigated. The catalytic performance was influenced by the anion of the ionic liquids for both substrate classes. A range of 2-alkyl-substituted 1,2,3,4-tetrahydroquinolines and 1-alkyl-substituted 1,2,3,4-tetrahydroisoquinolines was obtained in high yields with up to >99% ee. Interestingly, the hydrogenation of quinoline derivatives bearing a carbonyl group was selective for the C-N (quinoline) over the C-O (ketone) bonds, while such a unique chemoselectivity was not observed in methanol. Furthermore, the ruthenium catalysts could be easily recycled at least 5 times in the asymmetric hydrogenation of 3,4-dihydroisoquinoline by solvent extraction. To further facilitate the recovery of catalyst and reduce the use of organic solvent, a thin film of ionic liquid containing Ru(TsDPEN) was supported on silica gels. This supported ionic liquid-phase catalyst was effective in the asymmetric hydrogenation of quinoline, and could be recycled at least 6 times by simple filtration. Copyright
- Ding, Zi-Yuan,Wang, Tianli,He, Yan-Mei,Chen, Fei,Zhou, Hai-Feng,Fan, Qing-Hua,Guo, Qingxiang,Chan, Albert S. C.
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supporting information
p. 3727 - 3735
(2014/01/06)
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