- Molecular docking, 3D-QSAR, molecular dynamics, synthesis and anticancer activity of tyrosine kinase 2 (TYK 2) inhibitors
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A therapeutic rationale is proposed by selectively targeting tyrosine kinase 2 (TYK 2) to obtain potent TYK 2 inhibitors by molecular modeling studies. In the present study, we have taken tyrosine kinase (TYK 2) inhibitors and carried out molecular docking, 3 D quantitative structure–activity relationship (3D-QSAR) analysis and molecular dynamics (MD). Based on the 3D-QSAR results thirteen new compounds (R-1 to R-13) were designed and synthesized in good yields. The synthesized molecules were evaluated for their in vitro anticancer activity against LnCap and A549 cell lines. The molecules R-1, R-3, R-5, R-7, and R-10 exhibited considerable anti cancer activity.
- Itteboina, Ramesh,Ballu, Srilata,Sivan, Sree Kanth,Manga, Vijjulatha
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- Interrupted imino-nazarov cyclization of 1-aminopentadienyl cation and related cascade process
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Facile 4π conrotatory imino-Nazarov cyclization of a 1-aminopentadienyl cation generated from condensation an aldehyde and secondary aniline in the presence of a catalytic amount of a Lewis acid has been developed. Silver(I)-catalyzed intramolecular arene trapping of the resulting cyclic oxyallyl cation leads to formation of tricyclic indoline-fused cyclopentanone. The use of lanthanide salts allows transformation after the initial trapping to afford tetrahydroquinoline-fused cyclopentenone in a concise manner. Taking control: The fate of an oxyallyl cation formed through a 4π conrotatory imino-Nazarov cyclization can be controlled to access cyclopentanoid frameworks. In the presence of silver(I), intramolecular arene trapping leads to indoline-fused cyclopentanones. Gadolinium(III) facilitates a cascade transformation to furnish tetrahydroquinoline-fused cyclopentenones. Tf=trifluoromethanesulfonyl.
- William, Ronny,Wang, Siming,Ding, Feiqing,Arviana, Elise Nerissa,Liu, Xue-Wei
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- Reversing binding sensitivity to A147T translocator protein
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The translocator protein (TSPO) is a target for the development of neuroinflammation imaging agents. Clinical translation of TSPO PET ligands, such as [11C]DPA-713, has been hampered by the presence of a common polymorphism (A147T TSPO), at which all second-generation TSPO ligands lose affinity. Little is known about what drives binding at A147T compared to WT TSPO. This study aimed to identify moieties in DPA-713, and related derivatives, that influence binding at A147T compared to WT TSPO. We found changes to the nitrogen position and number in the heterocyclic core influences affinity to WT and A147T to a similar degree. Hydrogen bonding groups in molecules with an indole core improve binding at A147T compared to WT, a strategy that generated compounds that possess up to ten-times greater affinity for A147T. These results should inform the future design of compounds that bind both A147T and WT TSPO for use in neuroinflammation imaging.
- Banister, Samuel D.,Freelander, Isaac,Ittner, Lars M.,Kassiou, Michael,Reekie, Tristan A.,Vo, Sophie V.,Werry, Eryn L.
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- [(PPh3)2NiCl2]-Catalyzed C-N bond formation reaction via borrowing hydrogen strategy: Access to diverse secondary amines and quinolines
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Commercially available [(PPh3)2NiCl2] was found to be an efficient catalyst for the mono-N-alkylation of (hetero)- A romatic amines, employing alcohols to deliver diverse secondary amines, including the drug intermediates chloropyramine (5b) and mepyramine (5c), in excellent yields (up to 97%) via the borrowing hydrogen strategy. This method shows a superior activity (TON up to 10000) with a broad substrate scope at a low catalyst loading of 1 mol % and a short reaction time. Further, this strategy is also successful in accessing various quinoline derivatives following the acceptorless dehydrogenation pathway.
- Donthireddy,Pandey, Vipin K.,Rit, Arnab
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p. 6994 - 7001
(2021/06/09)
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- Mimicking transition metals in borrowing hydrogen from alcohols
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Borrowing hydrogen from alcohols, storing it on a catalyst and subsequent transfer of the hydrogen from the catalyst to anin situgenerated imine is the hallmark of a transition metal mediated catalyticN-alkylation of amines. However, such a borrowing hydrogen mechanism with a transition metal free catalytic system which stores hydrogen molecules in the catalyst backbone is yet to be established. Herein, we demonstrate that a phenalenyl ligand can imitate the role of transition metals in storing and transferring hydrogen molecules leading to borrowing hydrogen mediated alkylation of anilines by alcohols including a wide range of substrate scope. A close inspection of the mechanistic pathway by characterizing several intermediates through various spectroscopic techniques, deuterium labelling experiments, and DFT study concluded that the phenalenyl radical based backbone sequentially adds H+, H˙ and an electron through a dearomatization process which are subsequently used as reducing equivalents to the C-N double bond in a catalytic fashion.
- Banik, Ananya,Ahmed, Jasimuddin,Sil, Swagata,Mandal, Swadhin K.
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p. 8353 - 8361
(2021/07/02)
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- Switchable Imine and Amine Synthesis Catalyzed by a Well-Defined Cobalt Complex
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Switchable imine and amine synthesis catalyzed by a tripodal ligand-supported well-defined cobalt complex is presented herein. A large variety of primary alcohols and amines were selectively converted to imines or amines in good to excellent yields. It is discovered that the base plays a crucial role on the selectivity. A catalytic amount of base leads to the imine formation, while an excess loading of base results in the amine product. This strategy on product selectivity also strongly depends on the organometallic catalysts in use. We expect that the present study could provide useful insights toward selective organic synthesis and catalyst design.
- Paudel, Keshav,Xu, Shi,Hietsoi, Oleksandr,Pandey, Bedraj,Onuh, Chuka,Ding, Keying
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supporting information
p. 418 - 426
(2021/02/01)
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- Porous polymeric ligand promoted copper-catalyzed C-N coupling of (hetero)aryl chlorides under visible-light irradiation
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A porous polymeric ligand (PPL) has been synthesized and complexed with copper to generate a heterogeneous catalyst (Cu@PPL) that has facilitated the efficient C-N coupling with various (hetero)aryl chlorides under mild conditions of visible-light irradiation at 80 °C (58 examples, up to 99% yields). This method could be applied to both aqueous ammonia and substituted amines, and is compatible to a variety of functional groups and heterocycles, as well as allows tandem C-N couplings with conjunctive dihalides. Furthermore, the heterogeneous characteristic of Cu@PPL has enabled a straightforward catalyst separation in multiple times of recycling with negligible catalytic efficiency loss by simple filtration, affording reaction mixtures containing less than 1 ppm of Cu residue. [Figure not available: see fulltext.]
- Wang, Erfei,Chen, Kaixuan,Chen, Yinan,Zhang, Jiawei,Lin, Xinrong,Chen, Mao
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- Zinc-Catalyzed N-Alkylation of Aromatic Amines with Alcohols: A Ligand-Free Approach
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An efficient zinc-catalyzed N-alkylation reaction of aromatic amines was achieved using aliphatic, aromatic, and heteroaromatic alcohols as the alkylating reagent. A variety of aniline derivatives, including heteroaromatic amines, underwent the N-alkylation reaction and furnished the corresponding monoalkylated products in good to excellent yields. The application of the reaction is also further demonstrated by the synthesis of a 2-phenylquinoline derivative from acetophenone and 2-aminobenzyl alcohol. Deuterium labeling experiments show that the reaction proceeds via a borrowing hydrogen process. (Figure presented.).
- Sankar, Velayudham,Kathiresan, Murugavel,Sivakumar, Bitragunta,Mannathan, Subramaniyan
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supporting information
p. 4409 - 4414
(2020/09/01)
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- Scalable preparation of stable and reusable silica supported palladium nanoparticles as catalysts for N-alkylation of amines with alcohols
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The development of nanoparticles-based heterogeneous catalysts continues to be of scientific and industrial interest for the advancement of sustainable chemical processes. Notably, up-scaling the production of catalysts to sustain unique structural features, activities and selectivities is highly important and remains challenging. Herein, we report the expedient synthesis of Pd-nanoparticles as amination catalysts by the reduction of simple palladium salt on commercial silica using molecular hydrogen. The resulting Pd-nanoparticles constitute stable and reusable catalysts for the synthesis of various N-alkyl amines using borrowing hydrogen technology without the use of any base or additive. By applying this Pd-based catalyst, functionalized and structurally diverse N-alkylated amines as well as some selected drug molecules were synthesized in good to excellent yields. Practical and synthetic utility of this Pd-based amination protocol has been demonstrated by upscaling catalyst preparation and amination reactions to several grams-scales as well as recycling of catalyst. Noteworthy, this Pd-catalyst preparation has been up-scaled to kilogram scale and catalysts prepared in both small (1 g) and large-scale (kg) exhibited similar structural features and activity.
- Alshammari, Ahmad S.,Natte, Kishore,Kalevaru, Narayana V.,Bagabas, Abdulaziz,Jagadeesh, Rajenahally V.
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p. 141 - 149
(2020/01/06)
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- Base-mediated cascade amidination/: N -alkylation of amines by alcohols
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A base-mediated cascade amidination/N-alkylation reaction of amines by alcohols has been developed. For the first time, nitriles have been identified as an efficient and benign water acceptor reagent in N-alkylation. Notably, the procedure tolerates a series of functional groups, such as methoxyl, halo, vinyl and hetero groups, providing a convenient method to construct different substituted diamino compounds, 15N labeled amine and could be scaled up to 1 mol scale offering 138.7 g of the desired product in good yield in one-pot. Mechanistic studies provided strong evidence for the amidination of amines with nitriles facilitated by t-BuOK.
- Hu, Mao-Lin,Jia, Xiaofei,Liang, Zuyu,Lu, Fenghong,Zhang, Chunyan,Zhang, Guoying
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supporting information
p. 10489 - 10492
(2020/10/02)
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- Ruthenium(II) Complexes of Heteroditopic N-Heterocyclic Carbene Ligands: Efficient Catalysts for C-N Bond Formation via a Hydrogen-Borrowing Strategy under Solvent-Free Conditions
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Both imidazol-2-ylidene (ImNHC) and 1,2,3-triazol-5-ylidene (tzNHC) have evolved to be elite groups of N-heterocyclic carbene (NHC) ligands for homogeneous catalysis. To develop efficient ruthenium(II)-based catalysts incorporating these ligands for C-N bond-forming reactions via hydrogen-borrowing methodology, we utilized chelating ligands integrated with ImNHC and mesoionic tzNHC donors connected via a CH2 spacer with a diverse triazole backbone. The synthesized ruthenium(II) complexes 3 are found to be highly efficient for C-N bond formation across a wide range of primary amine and alcohol substrates under solvent-free conditions, and among all of the complexes studied here, catalyst 3a with a mesityl substituent displayed maximum activity. To our delight, catalyst 3a is also effective for the selective mono-N-methylation of various anilines utilizing methanol as a coupling partner, known to be relatively more difficult than other alcohols. Furthermore, complex 3a also delivers various substituted quinolines successfully via the reaction of 2-aminobenzyl alcohol with several secondary alcohols. Importantly, catalyst 3a exhibited the highest activity among the reported ruthenium(II) complexes for both the N-benzylation of aniline [achieving a turnover number (TON) of 50000] and the realization of quinoline 8a by reacting 2-aminobenzyl alcohol with 2-phenylethanol (attaining a TON of 30000).
- Donthireddy,Mathoor Illam, Praseetha,Rit, Arnab
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supporting information
p. 1835 - 1847
(2020/01/31)
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- In water alkylation of amines with alcohols through a borrowing hydrogen process catalysed by ruthenium nanoparticles
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A simple and environmentally benign procedure for the synthesis of secondary amines in water has been developed. Combining Ru3(CO)12, tetraphenylcyclopentadienone and a small quantity of TGPS-750-M surfactant, primary and secondary alcohols were alkylated at N employing equimolar amounts of aromatic amines in water. The reaction occurs under microwave (MW) dielectric heating with high conversion and high yield. When required, the use of biomass-derived 2-MeTHF or GVL as a co-solvent is possible. Under the influence of MWs, a Ru nanoparticle-nanomicelle combination was formed acting as an effective and recyclable catalyst. This protocol was also employed for "in water" cyclisation to synthesise biologically relevant pyrrolobenzodiazepines (PBDs).
- Risi, Caterina,Calamante, Massimo,Cini, Elena,Faltoni, Valentina,Petricci, Elena,Rosati, Filippo,Taddei, Maurizio
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supporting information
p. 327 - 331
(2020/02/13)
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- Direct electrochemical reductive amination between aldehydes and amines with a H/D-donor solvent
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A novel electrochemical synthesis protocol has been achieved for reductive amination between aldehydes and amines in undivided cells at room temperature. Under metal-free and external-reductant-free electrolysis conditions, various important secondary amine products are obtained in moderate-to-high yields. Deuterium-labeling experiments have demonstrated that low-toxicity DMSO acts both as a solvent and a H-donor in the reaction. On this basis, various deuterium-labeled products with good-to-excellent D-incorporation have been synthesized by using DMSO-d6 as a solvent. Furthermore, a molecule with GR-antagonistic activity has been synthesized through further sulfonylation.
- Chen, Lu,Hong, Huanliang,Hu, Jinhui,Huang, Yubing,Li, Yibiao,Liang, Gen,Pu, Suyun,Zhu, Zhongzhi,Zou, Zirong
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supporting information
p. 5832 - 5837
(2020/11/03)
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- Dehydrogenation and α-functionalization of secondary amines by visible-light-mediated catalysis
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A visible-light-mediated process for dehydrogenation of amines has been described. The given protocol showed a broad substrate scope, mild reaction conditions and excellent results without the requirement of tedious purification. This process can be applied in one-pot functionalization of secondary amines with various nucleophiles through the cooperation of visible-light and Lewis acid catalysis, leading to the structurally varied essential components of biologically active molecules. In addition, Stern-Volmer studies and quenching experiments revealed the role of a catalyst and led to the proposed mechanism of this transformation.
- Bujok, Robert,Morawska, Paulina,Pawlowski, Robert,Stanek, Filip,Stodulski, Maciej
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supporting information
p. 2103 - 2112
(2020/03/27)
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- Base-Mediated Amination of Alcohols Using Amidines
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Novel and efficient base-mediated N-alkylation and amidation of amidines with alcohols have been developed, which can be carried out in one-pot reaction conditions, which allows for the synthesis of a wide range of N-alkyl amines and free amides in good to excellent yields with high atom economy. In contrast to borrowing hydrogen/hydrogen autotransfer or oxidative-type N-alkylation reactions, in which alcohols are activated by transition-metal-catalyzed or oxidative aerobic dehydrogenation, the use of amidines provides an effective surrogate of amines. This circumvents the inherent necessity in N-alkylation of an oxidant or a catalyst to be stabilized by ligands.
- Chen, Jianbin,Fang, Yanchen,Jia, Xiaofei,Jiang, Shaohua,Li, Zehua,Liang, Zuyu,Lu, Fenghong,Qi, Shuo,Ren, Chaoyu,Yu, Shuangming,Zhang, Chunyan,Zhang, Guoying,Zhang, Sheng
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p. 7728 - 7738
(2020/07/15)
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- Simple reversible fixation of a magnetic catalyst in a continuous flow system: Ultrafast reduction of nitroarenes and subsequent reductive amination using ammonia borane
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Continuous reductive amination of aldehydes with nitroarenes over a Pd-Pt-Fe3O4 catalyst was performed. We used NH3BH3 as not only a hydrogen source for nitro reduction, but also a reductant for imine reduction. Secondary aromatic amines were obtained in the continuous flow reaction in good to excellent yields.
- Byun, Sangmoon,Cho, Ahra,Kang, Dong Yun,Kim, B. Moon,Kim, Ha Joon,Kim, Hong Won,Kim, Seong Min,Lei, Cao,Park, Jin Kyoon
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p. 944 - 949
(2020/03/11)
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- Fast continuous alcohol amination employing a hydrogen borrowing protocol
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A continuous flow method for the direct conversion of alcohols to amines via a hydrogen borrowing approach is reported. The method utilises a low loading (0.5%) of a commercial catalyst system ([Ru(p-cymene)Cl2]2 and DPEPhos), reagent grade solvent and is selective for primary alcohols. Successful methylation of amines using methanol and the direct dimethylamination of alcohols using commercial dimethylamine solution are reported. The synthesis of two pharmaceutical agents Piribedil (5) and Buspirone (25) were accomplished in good yields employing these new methods.
- Labes, Ricardo,Mateos, Carlos,Battilocchio, Claudio,Chen, Yiding,Dingwall, Paul,Cumming, Graham R.,Rincón, Juan A.,Nieves-Remacha, Maria José,Ley, Steven V.
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supporting information
p. 59 - 63
(2019/01/11)
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- Alcohol Amination Catalyzed by Copper Powder as a Self-Supported Catalyst
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Catalytic alcohol amination is a sustainable reaction for N-alkyl amine synthesis. Homogeneous and supported copper catalysts have long been studied for this reaction and have given some impressive results. In this study, copper powder is found to behave as an active catalyst for alcohol amination, giving better catalytic performance than metal-oxide-supported nanocopper catalysts. Catalyst characterization suggests that the copper powder can be considered as a self-supported nanocopper catalyst (i.e., nanocopper supported on copper particles). These results might promote the study of unsupported transition metal powders in sustainable catalytic reactions.
- Wu, Yajuan,Huang, Yongji,Dai, Xingchao,Shi, Feng
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p. 3185 - 3191
(2018/11/30)
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- Nickel-Catalyzed Asymmetric C-Alkylation of Nitroalkanes: Synthesis of Enantioenriched β-Nitroamides
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A general catalytic method for asymmetric C-alkylation of nitroalkanes using nickel catalysis is described. This method enables the formation of highly enantioenriched β-nitroamides from readily available α-bromoamides using mild reaction conditions that are compatible with a wide range of functional groups. When combined with subsequent reactions, this method allows access to highly enantioenriched products with nitrogen-bearing fully substituted carbon centers.
- Devannah, Vijayarajan,Sharma, Rajgopal,Watson, Donald A.
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supporting information
p. 8436 - 8440
(2019/06/13)
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- Ru-Catalyzed Deoxygenative Transfer Hydrogenation of Amides to Amines with Formic Acid/Triethylamine
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A ruthenium(II)-catalyzed deoxygenative transfer hydrogenation of amides to amines using HCO2H/NEt3 as the reducing agent is reported for the first time. The catalyst system consisting of [Ru(2-methylallyl)2(COD)], 1,1,1-tris(diphenylphosphinomethyl) ethane (triphos) and Bis(trifluoromethane sulfonimide) (HNTf2) performed well for deoxygenative reduction of various secondary and tertiary amides into the corresponding amines in high yields with excellent selectivities, and exhibits high tolerance toward functional groups including those that are reduction-sensitive. The choice of hydrogen source and acid co-catalyst is critical for catalysis. Mechanistic studies suggest that the reductive amination of the in situ generated alcohol and amine via borrowing hydrogen is the dominant pathway. (Figure presented.).
- Pan, Yixiao,Luo, Zhenli,Xu, Xin,Zhao, Haoqiang,Han, Jiahong,Xu, Lijin,Fan, Qinghua,Xiao, Jianliang
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supporting information
p. 3800 - 3806
(2019/07/12)
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- Continuous nitro-reduction and reductive amination reaction using ammoniaborane and magnetic nanoflakes immobilized through external magnetic force
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The present invention provides: a method of continuous reduction of a nitro compound which comprises continuously contacting a magnetic catalyst with a nitro compound and a reducing agent to reduce the nitro compound and continuously supplying an aldehyde compound thereto to continuously produce a secondary amine compound by conducting a reductive amination reaction; and an apparatus for the same.COPYRIGHT KIPO 2019
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Paragraph 0042-0052; 0061-0065
(2019/07/03)
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- Manganese-Catalyzed and Base-Switchable Synthesis of Amines or Imines via Borrowing Hydrogen or Dehydrogenative Condensation
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The use of earth-abundant transition metals as a noble metal replacement in catalysis is especially interesting if different catalytic reactivity is observed. We report, here, on the selective manganese-catalyzed base-switchable synthesis of N-alkylated amines or imines. In both reactions, borrowing hydrogen/hydrogen autotransfer (N-alkyl amine formation) or dehydrogenative condensation (imine formation), we start from the same amines and alcohols and use the same Mn precatalyst. The key is the presence of a potassium base to prefer N-alkylation and a sodium base to permit imine formation. Both bases react with the manganese hydride via deprotonation. The potassium manganate hydride reacts about 40 times faster with an imine to give the corresponding amine than the sodium manganate hydride. The selectivity seems unique for manganese complexes. We observe a broad scope with a complete product overlap, all amine alcohol combinations can be converted into an N-alkyl amine or an imine, and a good functional group tolerance.
- Fertig, Robin,Irrgang, Torsten,Freitag, Frederik,Zander, Judith,Kempe, Rhett
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p. 8525 - 8530
(2018/09/06)
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- MIL-101(Cr) as a synergistic catalyst for the reduction of imines with trichlorosilane
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The development of catalyst based on porous crystalline materials (PCM) constructed from metal ions or clusters and multidentate organic ligands is a topic of great interest. In view of the Lewis acidic and basic properties of PCMs, we report for the first time that MIL-101(Cr) works as a synergistic catalyst for the reduction of imines with trichlorosilane as the hydrogen source. Both ketimines and aldimines were tolerated with this protocol, giving the corresponding amines in moderate to high yields. The operational simplicity as well as mild reaction conditions renders this protocol an attractive approach for the synthesis of amines. Furthermore, a chiral MOF, CMIL-101, was also realized by grafting chiral N-formyl proline derivatives to the open metal sites. Moreover, CMIL-101 exhibited a comparable catalytic performance with its homogeneous counterpart in terms of yields and enantioselectivities.
- Chen, Jingwen,Chen, Xiaoling,Zhang, Zhiguo,Bao, Zongbi,Xing, Huabin,Yang, Qiwei,Ren, Qilong
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p. 163 - 169
(2018/01/05)
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- An Efficient Homogenized Ruthenium(II) Pincer Complex for N-Monoalkylation of Amines with Alcohols
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An ionic 2,6-bis(imidazo[1,2-α]pyridin-2-yl)pyridine-based N^N^N pincer ruthenium(II) complex exhibited high efficiency in the C–N bond formation between amines and alcohols by the “borrowing hydrogen” (BH) or “hydrogen autotransfer” (HA) concept. The synthetic protocol selectively generated monoalkylated amines without formation of tertiary amines during the reaction. The unique selectivity enabled the formation of symmetrically and asymmetrically substituted diamines. This methodology features several advantages including a low catalyst loading (as low as 0.5 mol-%), a short reaction time (as short as 2 h), and excellent N-monoalkylation selectivity.
- Yang, Fa-Liu,Wang, Ying-Hui,Ni, Yong-Feng,Gao, Xiang,Song, Bing,Zhu, Xinju,Hao, Xin-Qi
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p. 3481 - 3486
(2017/07/04)
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- A Base and Solvent-Free Ruthenium-Catalyzed Alkylation of Amines
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A (pyridyl)phosphine-ligated ruthenium(II) catalyst is reported for the chemoselective benzylic N-alkylation of amines, via a hydrogen-borrowing mechanism. The catalyst operates under mild conditions, neat, and without a base or other additive. These conditions offer remarkable functional group compatibility for applications in organic synthesis, including reactions involving phenols and anilines, which are very difficult to achieve. Mechanistic studies suggest that, unlike other catalysts for this reaction, the redox steps are fast and reversible while imine formation is slow. We perceive that this is the origin of the selectivity realized with these reaction conditions.
- Celaje, Jeff Joseph A.,Zhang, Xingyue,Zhang, Forrest,Kam, Lisa,Herron, Jessica R.,Williams, Travis J.
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p. 1136 - 1142
(2017/08/09)
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- Semi-quantitative models for identifying potent and selective transthyretin amyloidogenesis inhibitors
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Rate-limiting dissociation of the tetrameric protein transthyretin (TTR), followed by monomer misfolding and misassembly, appears to cause degenerative diseases in humans known as the transthyretin amyloidoses, based on human genetic, biochemical and pharmacologic evidence. Small molecules that bind to the generally unoccupied thyroxine binding pockets in the native TTR tetramer kinetically stabilize the tetramer, slowing subunit dissociation proportional to the extent that the molecules stabilize the native state over the dissociative transition state—thereby inhibiting amyloidogenesis. Herein, we use previously reported structure-activity relationship data to develop two semi-quantitative algorithms for identifying the structures of potent and selective transthyretin kinetic stabilizers/amyloidogenesis inhibitors. The viability of these prediction algorithms, in particular the more robust in silico docking model, is perhaps best validated by the clinical success of tafamidis, the first-in-class drug approved in Europe, Japan, South America, and elsewhere for treating transthyretin aggregation-associated familial amyloid polyneuropathy. Tafamidis is also being evaluated in a fully-enrolled placebo-controlled clinical trial for its efficacy against TTR cardiomyopathy. These prediction algorithms will be useful for identifying second generation TTR kinetic stabilizers, should these be needed to ameliorate the central nervous system or ophthalmologic pathology caused by TTR aggregation in organs not accessed by oral tafamidis administration.
- Connelly, Stephen,Mortenson, David E.,Choi, Sungwook,Wilson, Ian A.,Powers, Evan T.,Kelly, Jeffery W.,Johnson, Steven M.
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supporting information
p. 3441 - 3449
(2017/07/07)
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- Gold-Catalyzed Hydroarylation of N-Aryl Alkynamides for the Synthesis of 2-Quinolinones
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A mild method for the synthesis of 2-quinolinones via hydroarylation of N-aryl alkynamides is reported. While traditional methods have relied on the use of strong Br?nsted or Lewis acids, this report describes the development of mild reaction conditions that yield 2-quinolinones in good to excellent yield using a commercially available gold catalyst. Substrates bearing a variety of functional groups are presented, with N-substitution proving to be key to the reactivity of several substrates.
- Vacala, Taylor,Bejcek, Lauren P.,Williams, Chloé G.,Williamson, Alexandra C.,Vadola, Paul A.
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p. 2558 - 2569
(2017/03/14)
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- Double C-S bond formation: Via C-H bond functionalization: Synthesis of benzothiazoles and naphtho[2,1- d] thiazoles from N -substituted arylamines and elemental sulfur
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A novel, atom economic, and environmentally friendly method for the synthesis of 2-substituted benzothiazoles and 2-substituted naphtho[2,1-d]thiazoles from N-substituted arylamines and elemental sulfur has been developed under metal-free conditions. The reaction underwent the process of double C-S bond formation through C-H bond functionalization.
- Zhu, Xiaoming,Yang, Yuzhong,Xiao, Genhua,Song, Jianxin,Liang, Yun,Deng, Guobo
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supporting information
p. 11917 - 11920
(2017/11/06)
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- Buchwald–Hartwig Amination of Nitroarenes
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The Buchwald–Hartwig amination of nitroarenes was achieved for the first time by using palladium catalysts bearing dialkyl(biaryl)phosphine ligands. These cross-coupling reactions of nitroarenes with diarylamines, arylamines, and alkylamines afforded the corresponding substituted arylamines. A catalytic cycle involving the oxidative addition of the Ar?NO2 bond to palladium(0) followed by nitrite/amine exchange is proposed based on a stoichiometric reaction.
- Inoue, Fumiyoshi,Kashihara, Myuto,Yadav, M. Ramu,Nakao, Yoshiaki
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supporting information
p. 13307 - 13309
(2017/10/17)
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- Scalable synthesis of secondary and tertiary amines by heterogeneous Pt-Sn/γ-Al2O3catalyzed N-alkylation of amines with alcohols
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Synthesis of secondary and tertiary amines has been efficiently realized from the N-alkylation of amines with alcohols by means of heterogeneous bimetallic Pt-Sn/γ-Al2O3catalyst (0.5?wt % Pt, molar ratio Pt:Sn?=?1:3) through a borrowing hydrogen strategy. The Pt-Sn/γ-Al2O3catalyst has exhibited very high catalytic activity towards a wide range of amines and alcohols, and can be conveniently recycled without Pt metal leaching. The present protocol was applied for the synthesis of N-phenylbenzylamine in 96% isolated yield from aniline and benzyl alcohol on a 2.1?kg scale of the substrates, demonstrating its potential applicability for higher-order amine synthesis.
- Wu, Kaikai,He, Wei,Sun, Chenglin,Yu, Zhengkun
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supporting information
p. 8516 - 8521
(2016/11/28)
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- Implications of dynamic imine chemistry for the sustainable synthesis of nitrogen heterocycles via transimination followed by intramolecular cyclisation
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An exploration of a tandem approach to the sustainable synthesis of N-heterocycles from readily available N-aryl benzylamines or imines and ortho-substituted anilines is described, which demonstrates, for the first time, an important synthetic application of dynamic imine chemistry. The key features to the successful development of this protocol include the utilisation of N-aryl benzylamines as imine precursors in transimination, the occurrence of transimination in acetonitrile in the absence of any catalysts, an intramolecular nucleophilic addition occurring in the newly formed imine causing irreversible transimination, and the tandem event occurring under green conditions.
- Laha, Joydev K.,Satyanarayana Tummalapalli,Jethava, Krupal P.
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p. 2473 - 2479
(2016/03/01)
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- B(C6F5)3-Catalyzed Reductive Amination using Hydrosilanes
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In contrast to the established dogma that B(C6F5)3 is irreversibly poisoned by excess H2O/amine (or imine) bases, B(C6F5)3 is actually a water-tolerant catalyst for the reductive amination of primary and secondary arylamines with aldehydes and ketones in "wet solvents" at raised temperatures and using only 1.2 equiv of Me2PhSiH as reductant. Arylamines/N-arylimines do not result in the irreversible deprotonation of H2O-B(C6F5)3, allowing sufficient B(C6F5)3 to be evolved at raised temperatures to effect catalytic reductions. Stronger Br?nsted basic amines such as tBuNH2 (and derived imines) result in irreversible formation of [HO-B(C6F5)3]- from H2O-B(C6F5)3, precluding the formation of B(C6F5)3 at raised temperatures and thus preventing any imine reduction. A substrate scope exploration using 1 mol % nonpurified B(C6F5)3 and "wet solvents" demonstrates that this is an operationally simple and effective methodology for the production of secondary and tertiary arylamines in high yield, with imine reduction proceeding in preference to other possible reactions catalyzed by B(C6F5)3, including the dehydrosilylation of H2O and the reduction of carbonyl moieties (e.g., esters).
- Fasano, Valerio,Radcliffe, James E.,Ingleson, Michael J.
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p. 1793 - 1798
(2016/03/15)
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- A conjugated ketone as a catalyst in alcohol amination reactions under transition-metal and hetero-atom free conditions
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Here, we show the results of a molecular-defined conjugated ketone catalyzed alcohol amination reaction. Under the optimized reaction conditions, the yields to the desired products reached 98%. The reaction mechanism and kinetic study supposed that carbonyl-hydroxyl groups are the catalytically active sites, and the transfer-hydrogenation reactions progress via the recycling of carbonyl and hydroxyl groups. The catalytic process shows promise as an efficient and economic route for alcohol amination reactions.
- Dai, Xingchao,Cui, Xinjiang,Deng, Youquan,Shi, Feng
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p. 43589 - 43593
(2015/05/27)
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- Cobalt-Catalyzed Alkylation of Aromatic Amines by Alcohols
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The implementation of inexpensive, Earth-abundant metals in typical noble-metal-mediated chemistry is a major goal in homogeneous catalysis. A sustainable or green reaction that has received a lot of attention in recent years and is preferentially catalyzed by Ir or Ru complexes is the alkylation of amines by alcohols. It is based on the borrowing hydrogen or hydrogen autotransfer concept. Herein, we report on the Co-catalyzed alkylation of aromatic amines by alcohols. The reaction proceeds under mild conditions, and selectively generates monoalkylated amines. The observed selectivity allows the synthesis of unsymmetrically substituted diamines. A novel Co complex stabilized by a PN5P ligand catalyzes the reactions most efficiently. Sustainable C-N bond formation: An easily accessible Co complex efficiently catalyzes the alkylation of aromatic amines by alcohols. The mild reaction conditions permit the use of sensitive functional groups (I, Br) and the observed selective monoalkylation allows the synthesis of unsymmetrically alkylated diamines.
- R?sler, Sina,Ertl, Michael,Irrgang, Torsten,Kempe, Rhett
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supporting information
p. 15046 - 15050
(2016/01/25)
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- Tert-Butyl Hydroperoxide and Tetrabutylammonium Iodide-Promoted Free Radical Cyclization of α-Imino-N-arylamides and α-Azido-N-arylamides
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The oxidizing system of tert-butyl hydroperoxide (TBHP) and tetrabutylammonium iodide (TBAI) is capable of generating α-(arylaminocarbonyl)iminyl radicals from ethyl 2-(N-arylcarbamoyl)-2-iminoacetates. These iminyl radicals preferably undergo intramolecular ipso attack on the benzene ring to give azaspirocyclohexadienyl radicals, which are readily captured by molecular oxygen under an oxygen atmosphere to yield azaspirocyclohexadienones. In the absence of oxygen, the reaction affords quinoxalin-2-one products. This oxidizing system is also effective to convert α-aryl-α-azido-N-arylamides to the corresponding iminyl radicals under basic conditions (sodium tert-butoxide, t-BuONa), and the subsequent cyclization of these iminyl radicals results in the formation of azaspirocyclohexadienone products in high yields under an oxygen atmosphere. Plausible mechanisms are proposed to rationalize the experimental results, and factors influencing the reactions are discussed.
- Li, Dianjun,Yang, Tonghao,Su, Hailin,Yu, Wei
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supporting information
p. 2529 - 2539
(2015/08/18)
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- Rhenium-catalyzed amination of alcohols by hydrogen transfer process
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The rhenium heptahydride complex [ReH7(PCy3) 2] was found to be an effective homogeneous catalyst for amination of various alcohols through hydrogen transfer mechanism. Under carbon monoxide atmosphere, a variety of primary and secondary alcohols could directly undergo the CN coupling process.
- Abdukader, Ablimit,Jin, Hongming,Cheng, Yixiang,Zhu, Chengjian
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supporting information
p. 4172 - 4174
(2014/07/22)
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- New Iridium Catalysts for the Selective Alkylation of Amines by Alcohols under Mild Conditions and for the Synthesis of Quinolines by Acceptor-less Dehydrogenative Condensation
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A novel family of iridium catalysts stabilised by P,N-ligands have been introduced. The ligands are based on imidazo[1,5-b]pyridazin-7-amines and can be synthesised with a broad variety of substitution patterns. The catalysts were synthesised quantitatively from the protonated ligands and a commercially available iridium precursor. The catalysts mediate the alkylation of amines by alcohols under mild conditions (70 °C). In addition, the synthesis of quinolines from secondary or primary alcohols and amino alcohols is reported. This sustainable synthesis proceeds through the liberation of two equivalents of water and two equivalents of dihydrogen. The investigations indicate that catalysts suitable for hydrogen autotransfer or borrowing hydrogen chemistry might also be suitable for acceptor-less dehydrogenative condensation reactions. Your H or mine? A family of catalysts that mediate the alkylation of amines by alcohols under mild conditions are introduced (see scheme; HA=hydrogen autotransfer, BH=borrowing hydrogen, ADC=acceptor-less dehydrogenative condensation). The efficient synthesis of quinolines from alcohols and amino alcohols through the liberation of two equivalents of dihydrogen is also mediated by this catalyst family.
- Ruch, Susanne,Irrgang, Torsten,Kempe, Rhett
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supporting information
p. 13279 - 13285
(2016/02/19)
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- Synthesis of benzidine derivatives via FeCl3·6H 2O-promoted oxidative coupling of anilines
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Under open-flask conditions in the presence of commercially available FeCl3·6H2O, N,N-disubstituted anilines can be converted into diversely functionalized benzidines with yields of up to 99%. Oxidative coupling was extended to N-monosubstituted anilines, and the method was applied to the efficient preparation of 6,6′-biquinoline. Mechanistic investigations have also been performed to explain the observed reactivities.
- Ling, Xuege,Xiong, Yan,Huang, Ruofeng,Zhang, Xiaohui,Zhang, Shuting,Chen, Changguo
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p. 5218 - 5226
(2013/07/25)
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- Ligand-free CuSO4-catalyzed C-N coupling reaction of aryl halides with alkylamines or N-heterocycles in aqueous solution system
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C-N coupling can be achieved successfully under 80°C in aqueous nBu4NOH using CuSO4 as a catalyst. The study of substrate applicability demonstrated that the C-N coupling reaction of aryl iodides and bromides with alkylamines or N-heterocycles could be completed smoothly in this catalytic system.
- Yang, Hua,Zhang, Xiuli,Si, Jingyu
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p. 5647 - 5648
(2013/07/26)
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- Preparation of secondary and tertiary amines from nitroarenes and alcohols
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Various secondary amines were obtained selectively from the reaction of nitroarenes with primary alcohols in the presence of ruthenium(ii) complexes having phosphine-amine ligands as the catalyst. Secondary amines could be further alkylated with a primary alcohol using the same catalyst, but different conditions.
- Lee, Chun-Chin,Liu, Shiuh-Tzung
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supporting information; experimental part
p. 6981 - 6983
(2011/08/06)
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- Cu-catalyzed carbon-heteroatom coupling reactions under mild conditions promoted by resin-bound organic ionic bases
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Resin-bound organic ionic bases (RBOIBs) were developed in which tetraalkyl-ammonium or phosphonium cations are covalently attached to solid resins. The application tests showed that the performance of the tetraalkyl-ammonium-type RBOIBs is slightly better than that of the corresponding Cs salts in Cu-catalyzed C-N cross-couplings, while the tetraalkylphosphonium-type RBOIBs are significantly better than all the inorganic bases. With these newly developed RBOIBs, room-temperature Cu-catalyzed C-Ncoupling with various nonactivated aryl iodides and even aryl bromides can be readily accomplished. Moreover, RBOIBs can be easily recycled and reused for a number of times without much drop of activity. The good performances of RBOIBs are proposed to arise from the relatively weak binding forces between the cationic polymer backbone and basic anions, as opposed to the strong metal-anion interactions in the inorganic bases. Further applications of RBOIBs in Ni-catalyzed Suzuki-type couplings at room temperature, Cu-catalyzed C-N couplings at -30 °C, a Pd-catalyzed Heck reaction at 60 °C, and Cu-catalyzed C-S couplings at room temperature demonstrate that RBOIBs are generally applicable bases with improved performance for many other types of organic transformations.
- Huang, Yao-Bing,Yang, Chu-Ting,Yi, Jun,Deng, Xiao-Jian,Fu, Yao,Liu, Lei
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experimental part
p. 800 - 810
(2011/04/22)
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- New iridium catalysts for the efficient alkylation of anilines by alcohols under mild conditions
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The synthesis of eight new iridium complexes containing anionic P,N ligands is described. These complexes have been investigated as catalysts for amine alkylation reactions, resulting in a highly active catalyst for the selective monoalkylation of anilines with primary alcohols, under mild reaction conditions. Nearly quantitative conversion was observed at 70 °C with a catalyst loading as low as 0.05 mol % iridium. Selective amine alkylation: The synthesis of eight new iridium complexes containing anionic P,N ligands (see image) is described. These new complexes were used as highly active catalysts for the selective monoalkylation of anilines with primary alcohols, and gave nearly quantitative conversion under mild reaction conditions.
- Michlik, Stefan,Kempe, Rhett
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experimental part
p. 13193 - 13198
(2011/02/24)
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- C--H BOND AMINATION AND OLEFIN AZIRIDINATION WITH BETA-DIKETIMINATO COPPER CATALYSTS
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One aspect of the present invention relates to a method for the transition metal (e.g., Cu(I)) mediated amidation of C-H bonds using electron-rich aliphatic azides. In certain embodiments, the methods are useful for the C-H insertion of nitrenes generated and stabilized by a β-diketiminato metal catalyst. In certain embodiments, said nitrenes are generated from organoazides, or by oxidation of the corresponding amine. Another aspect of the present invention relates to olefin aziridination using said β-diketiminato metal catalysts. In addition, the methods of the present invention include stereoselective C-H bond aminations and olefin aziridinatons. In certain embodiments, the methods are conducted in an aerobic environment. In certain embodiments, the present invention relates to the use of O2 as an oxidant, wherein water is the byproduct of oxidation; this fact avoids the generation of toxic byproducts and renders the methods atom economical.
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Page/Page column 17
(2008/12/06)
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- One-pot reductive amination of aldehydes catalyzed by a hydrio-iridium(III) complex in aqueous medium
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A combination of sodium tetrakis[3,5-di(trifluoromethyl)phenyl]borate [NaBArF4] and hydrio-iridium(III) complex efficiently catalyzed the one-pot reductive amination of aldehydes with various amines and ammonia in water under mild conditions in good to excellent yields.
- Lai, Rung-Yi,Lee, Chun-I.,Liu, Shiuh-Tzung
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p. 1213 - 1217
(2008/09/17)
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- Aromatic amination of aryl bromides catalysed by copper/β-diketone catalysts: The effect of concentration
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CuCl ligated with β-diketones were found to be good catalysts for the animation of aryl bromides. Crucial is the concentration of the substrates: at 5 M the rate and selectivity improves substantially. In addition, K 2CO3 can be used as base instead of expensive Cs 2CO3. Primary and secondary amines, heterocycles and anilines could be arylated in good yields. Georg Thieme Verlag Stuttgart.
- De Lange, Ben,Lambers-Verstappen, Marielle H.,Schmieder-Van De Vondervoort, Lizette,Sereinig, Natascha,De Rijk, Ron,De Vries, André H. M.,De Vries, Johannes G.
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p. 3105 - 3109
(2008/02/13)
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- Highly selective room-temperature copper-catalyzed C-N coupling reactions
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Through the use of cyclic β-diketones as supporting ligands, the copper-catalyzed coupling of aryl iodides with aliphatic amines occurs at room temperature in as little as 1 h. These high reaction rates allow for the coupling of a wide range of aryl and heteroaryl iodides at room temperature. This method is highly tolerant of a number of reactive functional groups, including -Br and aromatic -NH2 as well as phenolic and aliphatic -OH. The high selectivity of the CuI-β-diketone catalyst for aliphatic amines represents a useful complement to the palladium-based methods. Copyright
- Shafir, Alexandr,Buchwald, Stephen L.
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p. 8742 - 8743
(2007/10/03)
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- Efficient photochemical synthesis of tricyclic keto-indoles
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Tricyclic keto-indoles were synthesized by photocyclization of easily obtained enaminones in an electrocyclic photochemical reaction. The three methods reported were chosen according to the enaminone structure. The most general procedure using one-step synthesis was carried out in a benzene-methanol solution in the presence of sodium methylate. In the case of base sensitive substrates, the best method was photocyclization followed by oxidation. Besides, N-unsubstituted indoles with a five-membered ring were prepared by a photolysis reaction. All three methods are efficient and easy to perform.
- Tietcheu, Christele,Garcia, Christophe,Gardette, Daniel,Dugat, Denise,Gramain, Jean-Claude
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p. 965 - 973
(2007/10/03)
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- Copper-catalyzed coupling of alkylamines and aryl iodides: an efficient system even in an air atmosphere.
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[reaction: see text] A mild method for the copper-catalyzed amination of aryl iodides is reported. This operationally simple C-N bond-forming protocol uses CuI as the catalyst and ethylene glycol as ligand in 2-propanol. A variety of functionalized aryl iodides as well as several amines were efficiently coupled using this method. This catalytic amination procedure is relatively insensitive to moisture and can be performed under an air atmosphere with comparable yield. Preliminary results on the amination of aryl bromides are also described.
- Kwong, Fuk Yee,Klapars, Artis,Buchwald, Stephen L
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p. 581 - 584
(2007/10/03)
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