- Modular, Self-Assembling Metallaphotocatalyst for Cross-Couplings Using the Full Visible-Light Spectrum
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The combination of nickel and photocatalysis has unlocked a variety of cross-couplings. These protocols rely on a few photocatalysts that can only convert a small portion of visible light (500 nm) into chemical energy. The high-energy photons that excite
- Reischauer, Susanne,Strauss, Volker,Pieber, Bartholom?us
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- I2/NaH2PO2-mediated deoxyamination of cyclic ethers for the synthesis of: N -aryl-substituted azacycles
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We have developed a protocol for efficient synthesis of N-aryl-substituted azacycles from aryl amines and cyclic ethers using I2/NaH2PO2 as the mediator. A diverse range of aryl amines and cyclic ethers undergo amination reaction to generate products in good to excellent yields with good functional group tolerance. This reaction can be easily scaled up to give N-aryl-substituted azacycles on a gram scale. Further chemical manipulation of the products enabled useful transformations of the quinoline ring, including bromination and acetylation. This journal is
- Chen, Tieqiao,Huang, Tianzeng,Li, Chunya,Li, Dongyang,Lin, Ying,Liu, Long,Tang, Zhi,Zhang, Jingjing
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supporting information
p. 21011 - 21014
(2021/12/04)
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- Dehydrogenation/(3+2) Cycloaddition of Saturated Aza-Heterocycles via Merging Organic Photoredox and Lewis Acid Catalysis
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Herein, we report a photoinduced dehydrogenation/(3+2) cycloaddition reaction by merging organic photoredox and Lewis acid catalysis, providing a straightforward and efficient approach for directly installing a benzofuran skeleton on the saturated aza-heterocycles. In this protocol, we also describe a novel organic photocatalyst (t-Bu-DCQ) with the advantages of a wider redox potential, easy synthesis, and a low price. Furthermore, the stepwise activation mechanism of dual C(sp3)-H bonds was demonstrated by a series of experimental and computational studies.
- Xiao, Teng-Fei,Zhang, Yi-Fan,Hou, Wen-Tao,Yan, Pen-Ji,Hai, Jun,Xu, Peng-Fei,Xu, Guo-Qiang
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supporting information
p. 8942 - 8946
(2021/11/24)
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- Organic photoredox catalytic α-C(sp3)-H phosphorylation of saturated: Aza -heterocycles
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A metal-free C(sp3)-H phosphorylation of saturated aza-heterocycles via the merger of organic photoredox and Br?nsted acid catalyses was established under mild conditions. This protocol provided straightforward and economic access to a variety of valuable α-phosphoryl cyclic amines by using commercially available diarylphosphine oxide reagents. In addition, the D-A fluorescent molecule DCQ was used for the first time as a photocatalyst and exhibited an excellent photoredox catalytic efficiency in this transformation. A series of mechanistic experiments and DFT calculations demonstrated that this transformation underwent a sequential visible light photoredox catalytic oxidation/nucleophilic addition process.
- Yi, Ming-Jun,Xiao, Teng-Fei,Li, Wen-Hui,Zhang, Yi-Fan,Yan, Pen-Ji,Zhang, Baoxin,Xu, Peng-Fei,Xu, Guo-Qiang
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supporting information
p. 13158 - 13161
(2021/12/16)
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- Ad Hoc Adjustment of Photoredox Properties by the Late-Stage Diversification of Acridinium Photocatalysts
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The steadily growing interest in substituting precious-metal photoredox catalysts with organic surrogates is vibrantly sustained by emerging methodologies to vary their photochemical behavior. Herein, we report an ad hoc approach for the preparation of acridinium salts with a particularly broad range of photoredox properties. The method involves an aryne-imine-aryne coupling to a linchpin tetrafluoro acridinium salt for a late-stage diversification by nucleophilic aromatic substitution reactions to form diaminoacridinium and undescribed aza-rhodol photocatalysts. The different functionalities and redox properties of the organic acridinium photocatalysts render them suitable for bifunctional photoredox catalysis and organocatalytic photochemical C-N cross-couplings.
- Hutskalova, Valeriia,Sparr, Christof
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supporting information
p. 5143 - 5147
(2021/06/30)
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- Tropane alkaloid compounds and method of manufacturing using sequential oxidation reactions
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The present invention relates to a tropane alkaloid compound sequentially using an oxidative Mannich ring reaction and a method for producing the same. The present invention provides a tropane alkaloid compound having a structure of chemical formula 1 in
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Paragraph 0098; 0165-0169
(2020/06/16)
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- Nickel-Catalyzed Amination of (Hetero)aryl Halides Facilitated by a Catalytic Pyridinium Additive
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An efficient and operationally simple Ni-catalyzed amination protocol has been developed. This methodology features a simple NiII salt, an organic base and catalytic amounts of both a pyridinium additive and Zn metal. A diverse number of (hetero)aryl halides were coupled successfully with primary and secondary alkyl amines, and anilines in good to excellent yields. Similarly, benzophenone imine gave the corresponding N-arylation product in an excellent yield.
- Han, Dongyang,Li, Sasa,Xia, Siqi,Su, Mincong,Jin, Jian
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supporting information
p. 12349 - 12354
(2020/09/09)
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- Visible Light-Mediated (Hetero)aryl Amination Using Ni(II) Salts and Photoredox Catalysis in Flow: A Synthesis of Tetracaine
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We report a visible light-mediated flow process for C-N cross-coupling of (hetero)aryl halides with a variety of amine coupling partners through the use of a photoredox/nickel dual catalyst system. Compared to the method in batch, this flow process enables a broader substrate scope, including less-activated (hetero)aryl bromides and electron-deficient (hetero)aryl chlorides, and significantly reduced reaction times (10 to 100 min). Furthermore, scale up of the reaction, demonstrated through the synthesis of tetracaine, is easily achieved, delivering the C-N cross-coupled products in consistently high yield of 84% on up to a 10 mmol scale.
- Park, Boyoung Y.,Pirnot, Michael T.,Buchwald, Stephen L.
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p. 3234 - 3244
(2020/02/04)
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- Synthesis method for converting lignin 4-O-5 model compound diaryl ether into nitrogen-containing compound
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The invention discloses a synthesis method for converting lignin 4-O-5 model compound diaryl ether into a nitrogen-containing compound. According to the synthesis method, a diaryl ether compound andan amine compound are subjected to a heating reaction in a certain amount of a solvent (containing a certain amount of water) in an argon atmosphere (containing a certain amount of air) under the actions of a metal catalyst and sodium borohydride, such that the drug with the important physiological activity or the compound with the natural product skeleton containing nitrogen is formed by directlycoupling the C-O bond cut and the amine compound cross while the corresponding aromatic hydrocarbon is obtained. According to the present invention, the synthesis method has characteristics of simpleand easily-available raw materials, high conversion rate, important product and good yield, and has broad application prospects in the degradation and deep development and utilization of lignin.
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Paragraph 0069-0071
(2019/04/26)
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- Nickel-Catalyzed Amide Bond Formation from Methyl Esters
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Despite being one of the most important and frequently run chemical reactions, the synthesis of amide bonds is accomplished primarily by wasteful methods that proceed by stoichiometric activation of one of the starting materials. We report a nickel-catalyzed procedure that can enable diverse amides to be synthesized from abundant methyl ester starting materials, producing only volatile alcohol as a stoichiometric waste product. In contrast to acid- and base-mediated amidations, the reaction is proposed to proceed by a neutral cross coupling-type mechanism, opening up new opportunities for direct, efficient, chemoselective synthesis.
- Ben Halima, Taoufik,Masson-Makdissi, Jeanne,Newman, Stephen G.
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supporting information
p. 12925 - 12929
(2018/09/14)
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- Electrochemically Driven, Ni-Catalyzed Aryl Amination: Scope, Mechanism, and Applications
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C-N cross-coupling is one of the most valuable and widespread transformations in organic synthesis. Largely dominated by Pd- and Cu-based catalytic systems, it has proven to be a staple transformation for those in both academia and industry. The current study presents the development and mechanistic understanding of an electrochemically driven, Ni-catalyzed method for achieving this reaction of high strategic importance. Through a series of electrochemical, computational, kinetic, and empirical experiments, the key mechanistic features of this reaction have been unraveled, leading to a second generation set of conditions that is applicable to a broad range of aryl halides and amine nucleophiles including complex examples on oligopeptides, medicinally relevant heterocycles, natural products, and sugars. Full disclosure of the current limitations and procedures for both batch and flow scale-ups (100 g) are also described.
- Kawamata, Yu,Vantourout, Julien C.,Hickey, David P.,Bai, Peng,Chen, Longrui,Hou, Qinglong,Qiao, Wenhua,Barman, Koushik,Edwards, Martin A.,Garrido-Castro, Alberto F.,Degruyter, Justine N.,Nakamura, Hugh,Knouse, Kyle,Qin, Chuanguang,Clay, Khalyd J.,Bao, Denghui,Li, Chao,Starr, Jeremy T.,Garcia-Irizarry, Carmen,Sach, Neal,White, Henry S.,Neurock, Matthew,Minteer, Shelley D.,Baran, Phil S.
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supporting information
p. 6392 - 6402
(2019/04/17)
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- Silver-catalyzed intermolecular amination of fluoroarenes
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A novel highly selective Ag-catalyzed intermolecular amination of fluoroarenes has been developed. This transformation starts from readily available 4-carbonyl fluorobenzene and NaN3 or other nitrogen-source, via amination followed by C-F bond cleavage, thus affording the desired 4-carbonyl arylamine products under mild conditions. The reaction is accelerated using a small amount of water. This pathway is distinct from a previously reported radical amination reaction.
- Wang, Yu,Wei, Chenlong,Tang, Ruyun,Zhan, Haosheng,Lin, Jing,Liu, Zhenhua,Tao, Weihua,Fang, Zhongxue
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supporting information
p. 6191 - 6194
(2018/09/10)
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- Palladium-Catalyzed Formal Cross-Coupling of Diaryl Ethers with Amines: Slicing the 4-O-5 Linkage in Lignin Models
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Lignin is the second most abundant organic matter on Earth, and is an underutilized renewable source for valuable aromatic chemicals. For future sustainable production of aromatic compounds, it is highly desirable to convert lignin into value-added platform chemicals instead of using fossil-based resources. Lignins are aromatic polymers linked by three types of ether bonds (α-O-4, β-O-4, and 4-O-5 linkages) and other C?C bonds. Among the ether bonds, the bond dissociation energy of the 4-O-5 linkage is the highest and the most challenging to cleave. To date, 4-O-5 ether linkage model compounds have been cleaved to obtain phenol, cyclohexane, cyclohexanone, and cyclohexanol. The first example of direct formal cross-coupling of diaryl ether 4-O-5 linkage models with amines is reported, in which dual C(Ar)?O bond cleavages form valuable nitrogen-containing derivatives.
- Zeng, Huiying,Cao, Dawei,Qiu, Zihang,Li, Chao-Jun
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p. 3752 - 3757
(2018/03/13)
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- Dual C(sp3)?H Bond Functionalization of N-Heterocycles through Sequential Visible-Light Photocatalyzed Dehydrogenation/[2+2] Cycloaddition Reactions
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Herein we describe a mild method for the dual C(sp3)?H bond functionalization of saturated nitrogen-containing heterocycles through a sequential visible-light photocatalyzed dehydrogenation/[2+2] cycloaddition procedure. As a complementary approach to the well-established use of iminium ion and α-amino radical intermediates, the elusive cyclic enamine intermediates were effectively generated by photoredox catalysis under mild conditions and efficiently captured by acetylene esters to form a wide array of bicyclic amino acid derivatives, thus enabling the simultaneous functionalization of two vicinal C(sp3)?H bonds.
- Xu, Guo-Qiang,Xu, Ji-Tao,Feng, Zhi-Tao,Liang, Hui,Wang, Zhu-Yin,Qin, Yong,Xu, Peng-Fei
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supporting information
p. 5110 - 5114
(2018/03/27)
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- Electrochemically Enabled, Nickel-Catalyzed Amination
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Along with amide bond formation, Suzuki cross-coupling, and reductive amination, the Buchwald–Hartwig–Ullmann-type amination of aryl halides stands as one of the most employed reactions in modern medicinal chemistry. The work herein demonstrates the potential of utilizing electrochemistry to provide a complementary avenue to access such critical bonds using an inexpensive nickel catalyst under mild reaction conditions. Of note is the scalability, functional-group tolerance, rapid rate, and the ability to employ a variety of aryl donors (Ar?Cl, Ar?Br, Ar?I, Ar?OTf), amine types (primary and secondary), and even alternative X?H donors (alcohols and amides).
- Li, Chao,Kawamata, Yu,Nakamura, Hugh,Vantourout, Julien C.,Liu, Zhiqing,Hou, Qinglong,Bao, Denghui,Starr, Jeremy T.,Chen, Jinshan,Yan, Ming,Baran, Phil S.
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supporting information
p. 13088 - 13093
(2017/09/25)
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- Metal-free Synthesis of Aryl Amines: Beyond Nucleophilic Aromatic Substitution
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A mild and metal-free approach to C?N coupling is described that employs diaryliodonium salt electrophiles and secondary aliphatic amine nucleophiles. This reaction results in direct ipso-substitution of the iodonium moiety and unsymmetrical aryl(TMP)iodonium salts are primarily employed. Moreover, arene substituents and substitution patterns that currently pose a challenge to classical metal-free methods are accommodated and the alicyclic amine nucleophiles used here are unprecedented in other contemporary metal-free C?N coupling reactions.
- Sandtorv, Alexander H.,Stuart, David R.
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p. 15812 - 15815
(2016/12/16)
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- Room-Temperature Practical Copper-Catalyzed Amination of Aryl Iodides
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An efficient and highly practical procedure is reported for the Ullmann-Goldberg-type copper-catalyzed amination of aryl iodides. By using a combination of copper iodide and proline in the presence of an excess of an amine, a wide range of aryl iodides can be readily aminated at room temperature. The reaction proceeds well regardless of the electronic properties of the starting aryl iodide and the amination products can be obtained without the need for purification by column chromatography in most cases. Owing to its efficiency and the mildness of the reaction conditions, this amination could also be extended to the amination of complex aryl iodides at room temperature.
- Deldaele, Christopher,Evano, Gwilherm
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p. 1319 - 1328
(2016/04/20)
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- Direct Acylation of C(sp3)-H Bonds Enabled by Nickel and Photoredox Catalysis
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Using nickel and photoredox catalysis, the direct functionalization of C(sp3)-H bonds of N-aryl amines by acyl electrophiles is described. The method affords a diverse range of α-amino ketones at room temperature and is amenable to late-stage coupling of complex and biologically relevant groups. C(sp3)-H activation occurs by photoredox-mediated oxidation to generate α-amino radicals which are intercepted by nickel in catalytic C(sp3)-C coupling. The merger of these two modes of catalysis leverages nickel's unique properties in alkyl cross-coupling while avoiding limitations commonly associated with transition-metal-mediated C(sp3)-H activation, including requirements for chelating directing groups and high reaction temperatures. Teamwork: The direct functionalization of C(sp3)-H bonds of N-aryl amines by acyl electrophiles is achieved, thus affording a diverse range of α-amino ketones at room temperature. C(sp3)-H activation occurs by photoredox-mediated oxidation to generate α-amino radicals which are intercepted by nickel in catalytic C(sp3)-C coupling.
- Joe, Candice L.,Doyle, Abigail G.
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supporting information
p. 4040 - 4043
(2016/03/19)
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- Photoredox α-vinylation of α-amino acids and N -aryl amines
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A new coupling protocol has been developed that allows the union of vinyl sulfones with photoredox-generated α-amino radicals to provide allylic amines of broad diversity. Direct C-H vinylations of N-aryl tertiary amines, as well as decarboxylative vinylations of N-Boc α-amino acids, proceed in high yield and with excellent olefin geometry control. The utility of this new allyl amine forming reaction has been demonstrated via the syntheses of several natural products and a number of established pharmacophores.
- Noble, Adam,MacMillan, David W. C.
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supporting information
p. 11602 - 11605
(2014/11/08)
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- Optimization of a small tropomyosin-related kinase B (TrkB) agonist 7,8-dihydroxyflavone active in mouse models of depression
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Structure-activity relationship study shows that the catechol group in 7,8-dihdyroxyflavone, a selective small TrkB receptor agonist, is critical for agonistic activity. To improve the poor pharmacokinetic profiles intrinsic to catechol-containing molecules and to elevate the agonistic effect of the lead compound, we initiated the lead optimization campaign by synthesizing various bioisosteric derivatives. Here we show that the optimized 2-methyl-8-(4′- (pyrrolidin-1-yl)phenyl)chromeno[7,8-d]imidazol-6(1H)-one derivative possesses enhanced TrkB stimulatory activity. Chronic oral administration of this compound significantly reduces the immobility in forced swim test and tail suspension test, two classical antidepressant behavioral animal models, which is accompanied by robust TrkB activation in hippocampus of mouse brain. Further, in vitro ADMET studies demonstrate that this compound possesses the improved features compared to the previous lead compound. Hence, this optimized compound may act as a promising lead candidate for in-depth drug development for treating various neurological disorders including depression.
- Liu, Xia,Chan, Chi-Bun,Qi, Qi,Ye, Keqiang,Xiao, Ge,Luo, Hongbo R.,He, Xiaolin
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supporting information
p. 8524 - 8537,14
(2020/09/15)
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- METHOD FOR COUPLING HALOGEN-SUBSTITUTED AROMATIC COMPOUNDS WITH ORGANIC COMPOUNDS COMPRISING TRIALKYLSILYL-SUBSTITUTED HETEROATOMS
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A process is provided for the preparation of aryl-heteroatom-bridged compounds by reacting a halogen-substituted aromatic compound with a trialkylsilyl-substituted heteroatom-containing organic compound.
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Page/Page column 6
(2012/06/16)
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- Microwave-assisted convenient synthesis of N-arylpyrrolidines in water
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An efficient and clean synthesis of N-arylpyrrolidines from arylamines and 1,4-dimesyloxybutane was developed using microwave irradiation in an aqueous potassium carbonate medium without any catalyst. The procedure is rapid, simple and convenient.
- Li, Hong Bo,Liang, Wu,Liu, Lang,Chen, Kai,Wu, Yi
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experimental part
p. 276 - 279
(2012/01/05)
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- Mild transition-metal-free amination of fluoroarenes catalyzed by fluoride ions
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Trimethylsilyl-protected heterocycles undergo N-C bond formation with a variety of electron-deficient fluoroarenes catalyzed by fluoride ions. This reaction avoids stoichiometric amounts of base and thus makes N-arylheterocycles accessible in a very mild and transition-metal-free way.
- Dehe, Daniel,Munstein, Isabel,Reis, Andreas,Thiel, Werner R.
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experimental part
p. 1151 - 1154
(2011/05/02)
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- Ruthenium-catalyzed /V-alkylation of amines and sulfonamides using borrowing hydrogen methodology
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The alkylation of amines by alcohols has been achieved using 0.5 mol percent [Ru(p-cymene)CI2]2 with the bidentate phosphines dppf or DPEphos as the catalyst. Primary amines have been converted into secondary amines, and secondary amines into tertiary amines, including the syntheses of Piribedil, Tripelennamine, and Chlorpheniramine. A/-Heterocyclization reactions of primary amines are reported, as well as alkylation reactions of primary sulfonamides. Secondary alcohols requiremore forcing conditions than primary alcohols but are still effective a lkylating agents in the presence of this catalyst.
- Hamid, M. Haniti S. A.,Allen, C. Liana,Lamb, Gareth W.,Maxwell, Aoife C.,Maytum, Hannah C.,et al.
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supporting information; experimental part
p. 1766 - 1774
(2009/07/25)
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- Cysteine protease inhibitors
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of the formula (IV): where: R1=R′C(O), R′SO2, R′=a bicyclic, saturated or unsaturated, 8-12 membered ring system containing 0-4 hetero atoms selected from S, O and N, which is optionally substituted with up to four substituents independently selected from groups a), b) and c) below; or R′=a monocyclic, saturated or unsaturated, 5-7 membered ring containing 0-3 hetero atoms selected from S, O and N, which monocyclic ring bears at least one substituent selected from group a) and/or c) and which may optionally bear one or two further substituents selected from group b); R4=H, C1-7-alkyl, Ar-C1-7-alkyl, Ar, C3-7-cycloalkyl; C2-7alkenyl; R3=C1-7-alkyl, C2-C7 alkenyl, C2-C7 alkenyl, C3-7-cycloalkyl, Ar-C1-7-alkyl, Ar; R5=C1-7-alkyl, halogen, Ar-C1-7-alkyl, C1-3-alkyl-CONR3R4 or a bulky amine R6 is H, C1-7-alkyl, Ar-C1-7-alkyl, C1-3-alkyl-SO2-Rix, C1-3-alkyl-C(O)—NHRix or CH2XAr q is 0 or 1 have utility as inhibitors of cysteine proteases such as cathepsin K and falcipain.
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