- Effect of the ancillary ligand in N-heterocyclic carbene iridium(III) catalyzed N-alkylation of amines with alcohols
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A series of air-stable N-heterocyclic carbene (NHC) Ir(III) complexes (Ir1-6), bearing various combinations of chlorine, pyridine and NHC ligands, were assayed for the N-alkylation of amines with alcohols. It was found that Ir3, with two monodentate 1,3-bis-methyl-imidazolylidene (IMe) ligands, emerged as the most active complex. A large variety of amines and primary alcohols were efficiently converted into mono-N-alkylated amines in 53–96% yields. As a special highlight, for the challenging MeOH, selective N-monomethylation could be achieved using KOH as a base under an air atmosphere. Moreover, this catalytic system was successfully applied to the gram-scale synthesis of some valuable compounds.
- Feng, Xinshu,Huang, Ming
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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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- Ruthenium(ii) complexes with N-heterocyclic carbene-phosphine ligands for theN-alkylation of amines with alcohols
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Metal hydride complexes are key intermediates forN-alkylation of amines with alcohols by the borrowing hydrogen/hydrogen autotransfer (BH/HA) strategy. Reactivity tuning of metal hydride complexes could adjust the dehydrogenation of alcohols and the hydrogenation of imines. Herein we report ruthenium(ii) complexes with hetero-bidentate N-heterocyclic carbene (NHC)-phosphine ligands, which realize smart pathway selection in theN-alkylated reactionviareactivity tuning of [Ru-H] species by hetero-bidentate ligands. In particular, complex6cbwith a phenyl wingtip group and BArF?counter anion, is shown to be one of the most efficient pre-catalysts for this transformation (temperature is as low as 70 °C, neat conditions and catalyst loading is as low as 0.25 mol%). A large variety of (hetero)aromatic amines and primary alcohols were efficiently converted into mono-N-alkylated amines in good to excellent isolated yields. Notably, aliphatic amines, challenging methanol and diamines could also be transformed into the desired products. Detailed control experiments and density functional theory (DFT) calculations provide insights to understand the mechanism and the smart pathway selectionvia[Ru-H] species in this process.
- Huang, Ming,Li, Yinwu,Lan, Xiao-Bing,Liu, Jiahao,Zhao, Cunyuan,Liu, Yan,Ke, Zhuofeng
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supporting information
p. 3451 - 3461
(2021/05/03)
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- Pyridine mediated transition-metal-free direct alkylation of anilines using alcohols: via borrowing hydrogen conditions
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Herein, we report pyridine and other similar azaaromatics as efficient biomimetic hydrogen shuttles for a transition-metal-free direct N-alkylation of aryl and heteroaryl amines using a variety of benzylic and straight chain alcohols. Mechanistic studies including deuterium labeling and the isolation of dihydro-intermediates of the benzannulated pyridine confirmed the role of pyridine and a borrowing hydrogen process operating in these reactions. In addition, we have extended this methodology for the development of dehydrogenative synthesis of quinolines and indoles, as well as the transfer hydrogenation of ketones. This journal is
- Pothikumar, Rajagopal,Bhat, Venugopal T,Namitharan, Kayambu
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supporting information
p. 13607 - 13610
(2020/11/17)
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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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- A bifunctional strategy for N-heterocyclic carbene-stabilized iridium complex-catalyzed: N -alkylation of amines with alcohols in aqueous media
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Through the strategy of combining bifunctional 2-hydroxypyridine and a thermally stable N-heterocyclic carbene ligand, an Ir-catalyzed N-monoalkylation reaction has been developed in aqueous media under base-free conditions. This reaction proceeds smoothly with high yields of various aromatic amines and sulfonamides with a wide range of primary alcohols. Experimental and computational studies revealed a metal-ligand cooperative mechanism and its thermal stability during the bifunctional catalysis in aqueous media.
- Huang, Ming,Li, Yinwu,Liu, Jiahao,Lan, Xiao-Bing,Liu, Yan,Zhao, Cunyuan,Ke, Zhuofeng
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supporting information
p. 219 - 224
(2019/01/28)
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- Room temperature N-heterocyclic carbene manganese catalyzed selective N-alkylation of anilines with alcohols
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The first example of room temperature non-noble metal homogeneous system catalyzed selective N-alkylation of anilines with alcohols by a bis-NHC manganese complex is presented. This system was applied to a large range of alcohols and anilines, including biologically relevant motifs and challenging methanol. Experimental and computational studies suggest an outer-sphere mechanism for this NHC-Mn system.
- Huang, Ming,Li, Yukui,Li, Yinwu,Liu, Jiahao,Shu, Siwei,Liu, Yan,Ke, Zhuofeng
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supporting information
p. 6213 - 6216
(2019/06/07)
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- Phosphorous(v) Lewis acids: Water/base tolerant P3-trimethylated trications
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The water/base intolerance of the previously reported electrophilic phosphonium cations has been overcome by replacing the labile electron-withdrawing groups generally attached to phosphorus (e.g. -F, -OAr, -CF3) with methyl groups. Tri-phosphorus(v) tricationic species, accessible in one-pot from commercially available materials, are air and water/base tolerant, yet are sufficiently Lewis acidic for catalysis.
- Bayne,Fasano,Szkop,Ingleson,Stephan
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supporting information
p. 12467 - 12470
(2018/11/20)
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- Metal- and Base-Free Room-Temperature Amination of Organoboronic Acids with N-Alkyl Hydroxylamines
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We have found that readily available N-alkyl hydroxylamines are effective reagents for the amination of organoboronic acids in the presence of trichloroacetonitrile. This amination reaction proceeds rapidly at room temperature and in the absence of added metal or base, it tolerates a remarkable range of functional groups, and it can be used in the late-stage assembly of two complex units.
- Sun, Hong-Bao,Gong, Liang,Tian, Yu-Biao,Wu, Jin-Gui,Zhang, Xia,Liu, Jie,Fu, Zhengyan,Niu, Dawen
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supporting information
p. 9456 - 9460
(2018/07/29)
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- Expedient Access to 2-Benzazepines by Palladium-Catalyzed C?H Activation: Identification of a Unique Hsp90 Inhibitor Scaffold
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Bioactive 2-benzazepines were accessed in an atom- and step-economical manner through a versatile palladium-catalyzed C?H activation strategy. The C?H arylation required low catalyst loading and a mild base, which was reflected by a broad scope and high functional-group tolerance. The benzotriazolodiazepinones were identified as new heat shock protein 90 (Hsp90) inhibiting lead compounds, with considerable potential for anti-cancer applications.
- Virelli, Matteo,Moroni, Elisabetta,Colombo, Giorgio,Fiengo, Lorenzo,Porta, Alessio,Ackermann, Lutz,Zanoni, Giuseppe
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supporting information
p. 16516 - 16520
(2018/10/25)
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- Direct Reductive Amination of Aldehydes via Environmentally Benign Bentonite-Gold Nanohybrid Catalysis
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An efficient, green and reliable method for the direct reductive amination of aldehydes was developed using an environmentally benign bentonite-gold nanohybrid catalyst. Use of this heterogeneous catalyst affords a variety of secondary amines in excellent yield under ambient reaction conditions in the presence of phenyldimethylsilane as mild hydride donor. The catalyst is recyclable, selective and is well applicable for the gram-scale preparation of secondary amines. (Figure presented.).
- Maya,Poulose, Susanna,John, Jubi,Luxmi Varma
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p. 1177 - 1184
(2017/04/11)
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- Rhodium-Catalyzed Enantioselective Reductive Arylation: Convenient Access to 3,3-Disubstituted Oxindoles
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A rhodium-Josiphos(L*) catalyzed enantioselective intramolecular hydroarylation reaction is described. The reductive cyclization of o-bromoaniline-derived acrylamides provides convenient access to 3,3-disubstituted oxindoles in good yields and with excell
- Jang, Young Jin,Larin, Egor M.,Lautens, Mark
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p. 11927 - 11930
(2017/09/20)
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- Unexpected Rearrangement of 2-Bromoaniline under Biphasic Alkylation Conditions
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Alkylation of 2-bromoaniline with benzyl bromide under ostensibly basic N-alkylation conditions resulted in migration of bromine from the 2- to the 4-aryl position. Herein we report our studies to elucidate the mechanism of this rearrangement with the objective of suppressing this unexpected outcome. We find that careful choice of reagents is critical, and that this behavior may be extrapolated to alkylation reactions of electron-rich bromo- and iodoanilines in general.
- Barraza, Scott J.,Denmark, Scott E.
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p. 2891 - 2895
(2017/10/06)
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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 Simple Cobalt(II) Chloride Catalyzed N -Alkylation of Amines with Alcohols
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A facile cobalt-catalyzed N -alkylation of amines with alcohols using inexpensive, commercially available CoCl 2 ·6H 2 O is reported. Employing this readily available cobalt catalyst, a variety of amines with wide functional group tolerance were selectively alkylated under benign conditions.
- Midya, Siba P.,Mondal, Akash,Begum, Ayesha,Balaraman, Ekambaram
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supporting information
p. 3957 - 3961
(2017/08/29)
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- One-pot strategy of copper-catalyzed synthesis of 1,2-disubstituted benzimidazoles
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A simple, one-pot and copper-catalyzed coupling reaction for the construction of 1,2-disubstituted benzimidazole derivatives is described. A low-cost copper salt and a weak base K3PO4 were utilized in this reaction. A variety of 1,2-disubstituted benzimidazoles were obtained in moderate to excellent yields.
- Xie, Caixia,Han, Xushuang,Gong, Jian,Li, Danyang,Ma, Chen
-
supporting information
p. 5811 - 5819
(2017/07/22)
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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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- Efficient hydrosilylation of imines using catalysts based on iridium(iii) metallacycles
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Ir(iii) metallacycles were applied as catalysts for the hydrosilylation of various ketimines and aldimines with sodium tetrakis[(3,5-trifluoromethyl)phenyl]borate, NaBArF24, as an additive. By using a slight excess of the organosilane reagent, the reactions proceeded rapidly and efficiently, at low catalyst loadings and at room temperature. Several examples of cationic Ir(iii) catalysts could be synthesised, characterized and tested. In situ-generated catalysts proved to be more active as compared to isolated ones and species with non-coordinating BArF24 counterion gave the highest catalytic activities.
- Corre,Iali,Hamdaoui,Trivelli,Djukic,Agbossou-Niedercorn,Michon
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p. 1452 - 1458
(2015/04/14)
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- Direct Alkylation of Amines with Alcohols Catalyzed by Base
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A base-catalyzed/promoted transition-metal-free direct alkylation of amines with alcohols has been developed, giving the desired amines in generally high yields from either aromatic or aliphatic alcohols. On the basis of the 1H NMR and in situ IR (React-IR) monitoring experiments, isotope-labeling experiments, as well as control experiments, a novel "hemiaminal" model is proposed to understand the mechanism, which explains the formation of the "extra" aldehyde in the reaction.
- Li, Qiang-Qiang,Xiao, Zu-Feng,Yao, Chuan-Zhi,Zheng, Hong-Xing,Kang, Yan-Biao
-
supporting information
p. 5328 - 5331
(2015/11/18)
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- Copper catalyzed sequential arylation-oxidative dimerization of o-haloanilides: synthesis of dimeric HPI alkaloids
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In this communication, we report a copper catalyzed sequential arylation-oxidative dimerization reaction as the key step for the synthesis of hexahydropyrroloindole alkaloids (+)-chimonanthine, (+)-folicanthine and (-)-calycanthine.
- Shen, Xianfu,Zhou, Yongyun,Xi, Yongkai,Zhao, Jingfeng,Zhang, Hongbin
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p. 14873 - 14876
(2015/10/06)
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- Sulfate Radical Anion (SO4?-) Mediated C(sp3)-H Nitrogenation/Oxygenation in N-Aryl Benzylic Amines Expanded the Scope for the Synthesis of Benzamidine/Oxazine Heterocycles
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A transition-metal-free, K2S2O8-mediated intramolecular oxidative nitrogenation/oxygenation of C(sp3)-H in N-aryl benzylic amines followed by oxidation at the benzylic center has been developed for the synthesis of benzamidine/benzoxazine heterocycles, providing an expedient access to quinazolin-4(3H)-ones, N-aryl-2-arylbenzimidazoles, and 4H-3,1-benzoxazin-4-ones. A considerable amount of work dealing with the mechanistic study to understand the crucial intramolecular cyclization step largely favors an iminium ion as the key intermediate.
- Laha, Joydev K.,Tummalapalli, K. S. Satyanarayana,Nair, Akshay,Patel, Nidhi
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p. 11351 - 11359
(2015/12/01)
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- Self-induced stereoselective in situ trifluoromethylation: Preparation of spiro[indoline-3,3′-quinoline] via palladium-catalyzed cascade reaction
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An efficient method to prepare 1′H-spiro[indoline-3,3′- quinoline]-2′,4′-diones and their trifluoromethylated products was developed via a palladium-catalyzed Sonogashira coupling/Wacker-type oxypalladation/cyclization cascade reaction. The amount of wate
- Song, Hongjian,Liu, Yongxian,Liu, Yuxiu,Wang, Qingmin
-
supporting information
p. 3240 - 3243
(2014/07/08)
-
- Direct reductive amination using triethylsilane and catalytic bismuth(III) chloride
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Direct reductive amination (DRA) using triethylsilane (TESH) and catalytic bismuth(III) chloride (BiCl3) is described for the first time. The use of TESH and BiCl3 provides easy handling, low cost, non-toxicity, and a mild Lewis acid activity, thereby meeting the demand for green and sustainable chemistry. The developed DRA is highly chemoselective and applicable to less-basic amines. The experimental results of this study revealed that the developed DRA could be catalyzed by BiCl3, which was gradually reduced to Bi(0) or bismuth with a low valency by TESH, but TESCl, Bi(0), and Bi(0) with TESCl catalyzed the DRA to some extent.
- Matsumura, Takehiko,Nakada, Masahisa
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p. 1829 - 1834
(2014/03/21)
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- General and selective reductive amination of carbonyl compounds using a core-shell structured Co3O4/NGr@C catalyst
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The application of heterogenized non-noble metal-based catalysts in selective catalytic hydrogenation processes is still challenging. In this respect, the preparation of a well-defined cobalt-based catalyst was investigated by immobilization of the corresponding cobalt(ii)-phenanthroline-chelate on Vulcan XC72R carbon powder. The formed core-shell structured cobalt/cobalt oxide nanocomposites are encapsulated by nitrogen-enriched graphene layers. This promising cheap heterogeneous catalyst allows for an efficient domino reductive amination of carbonyl compounds with nitroarenes. This journal is
- Stemmler, Tobias,Westerhaus, Felix A.,Surkus, Annette-Enrica,Pohl, Marga-Martina,Junge, Kathrin,Beller, Matthias
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p. 4535 - 4540
(2014/12/10)
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- Transition-metal-free tandem oxidative removal of benzylic methylene group by C-C and C-N bond cleavage followed by intramolecular new aryl C-N bond formation under radical conditions
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A novel tandem oxidative conversion of 10,11-dihydro-5H-dibenzo[b,e][1,4]diazepines to phenazines has been achieved under transition-metal-free, mild conditions using K2S2O8 or DDQ as the oxidizing agent. The transformation proceeds through oxidative removal of a benzylic methylene group by C-C and C-N bond cleavage followed by a new aryl C-N bond formation under radical conditions.
- Laha, Joydev K.,Tummalapalli, K. S. Satyanarayana,Gupta, Ankur
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supporting information
p. 4392 - 4395
(2015/01/08)
-
- Thermal switchability of N-chelating hoveyda-type catalyst containing a secondary amine ligand
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An investigation of aza analogues of the popular Hoveyda-Grubbs catalyst containing a secondary amine ligand is presented, proving the crucial impact of steric as well as electronic factors on the catalyst's stability and performance. The issue of latency in the reactivity profile of studied catalysts is examined, followed by structural and application studies.
- Zukowska, Karolina,Szadkowska, Anna,Pazio, Aleksandra E.,Wo?niak, Krzysztof,Grela, Karol
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experimental part
p. 462 - 469
(2012/04/23)
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- Selective N-alkylation of arylamines with alkyl chloride in ionic liquids: Scope and applications
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An efficient N-selective alkylation of primary aromatic amines in molten quaternary ammonium salts, as the solvent, under relatively mild and base-free conditions is presented. On the basis of the Kamlet-Taft parameters and the nucleophilicity of the IL (ionic liquid) anions, the influence of the ionic liquid was evaluated. This protocol was validated on a larger multigram scale and with the syntheses of bioactive heterocycles (e.g., 1,4-benzothiazine and quinoxalines) and new efficient MALDI matrixes. Copyright
- Monopoli, Antonio,Cotugno, Pietro,Cortese, Marina,Calvano, Cosima Damiana,Ciminale, Francesco,Nacci, Angelo
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supporting information; experimental part
p. 3105 - 3111
(2012/06/30)
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- Direct reductive amination of aromatic aldehydes catalyzed by gold(i) complex under transfer hydrogenation conditions
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The direct reductive amination of aromatic aldehydes has been achieved with excellent isolated yields (89-96%) using readily accessible Ph 3PAuCl/AgOTf catalyst along with ethyl Hantzsch ester as hydrogen source under mild reaction conditions.
- Zhang, Ming,Yang, Hongwei,Zhang, Yan,Zhu, Chengjian,Li, Wei,Cheng, Yixiang,Hu, Hongwen
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supporting information; experimental part
p. 6605 - 6607
(2011/07/08)
-
- Potassium tert-butoxide promoted intramolecular arylation via a radical pathway
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Potassium tert-butoxide mediated intramolecular cyclization of aryl ethers, amines, and amides was efficiently performed under microwave irradiation to provide the corresponding products in high regioisomeric ratios. The reaction proceeds via single-electron transfer to initiate the formation of an aryl radical, followed by a kinetically favored 5-exo-trig and subsequent ring expansion.
- Roman, Daniela Sustac,Takahashi, Yoko,Charette, Andre B.
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supporting information; experimental part
p. 3242 - 3245
(2011/08/02)
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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)
-
- Rhodium-catalyzed domino conjugate addition-cyclization reactions for the synthesis of a variety of N- and O-heterocycles: Arylboroxines as effective carbon nucleophiles
-
Facile and efficient Rh(I)-catalyzed domino conjugate addition-cyclization reactions of olefins bearing two electrophilic sites and a pendant nucleophile with organoboroxines have been developed to afford a variety of N- and O-heterocycles, such as 3,4-dihydroquinolin-2(1H)-ones, 3,4-dihydrocoumarins, and pyrrolidin-2-ones, which constitute important motifs in biologically active natural and synthetic organic compounds.
- Park, Ja Ock,Youn, So Won
-
supporting information; experimental part
p. 2258 - 2261
(2010/07/17)
-
- IBiox[(-)-menthyl]: A sterically demanding chiral NHC ligand
-
(Figure Presented) An exceedingly sterically demanding, rigid, and chiral NHC ligand, IBiox[(-)-menthyl] (1), was prepared and structurally characterized. With a buried volume of 50percent, this ligand arguably represents one of the most sterically demanding monodentate ligands. The ability to use aryl chloride substrates in intramolecular palladium-catalyzed ,-arylations reveals its unique reactivity. Moreover, C2-symmetric 1 allows the highly enantioselective formation of oxindoles withup to 99percent ee.
- Wuertz, Sebastian,Lohre, Claudia,Froehlich, Roland,Bergander, Klaus,Glorius, Frank
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supporting information; experimental part
p. 8344 - 8345
(2009/10/24)
-
- Copper-catalyzed intramolecular N-arylation of ureas in water: a novel entry to benzoimidazolones
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The copper-catalyzed intramolecular N-arylation of 2-bromoarylureas performed in water leading to the benzo[d]imidazolone framework is reported. The scope of the methodology presented herein proved to?be broad and afforded a significant number of benzoimidazolones in good to excellent yields. The reported protocol is based on the use of CuI and TMEDA acting both as the ligand and as the base in a water solution, which allows for the easy separation of the catalyst containing aqueous phase from the products by simple extraction. Additionally, the N- versus O-arylation competitive processes are also discussed.
- Barbero, Nekane,Carril, Mónica,SanMartin, Raul,Domínguez, Esther
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p. 7283 - 7288
(2008/09/21)
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- FUSED AND SPIROCYCLE COMPOUNDS AND THE USE THEREOF
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The invention relates to fused and spirocycle compounds of Formula (I), or a pharmaceutically acceptable salt, prodrug, or solvate thereof, wherein R1, R2, Q1-Q3, and Z are defined as set forth in the specification. The invention is also directed to the use of compounds of Formula (I) to treat, prevent or ameliorate a disorder responsive to the blockade of calcium channels, and particularly N-type calcium channels. Compounds of the present invention are especially useful for treating pain.
- -
-
Page/Page column 94
(2008/06/13)
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- Indole synthesis by controlled carbolithiation of o-aminostyrenes
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An effective synthesis of the functionalized indole ring system has been developed from substituted o-aminostyrene starting material. Our methodology involves a novel cascade reaction sequence of alkyllithium addition to the styrene double bond and subsequent trapping of the intermediate organolithium with a suitable electrophile, followed by an in situ ring closure and dehydration to generate the indole ring. This new reaction sequence allows for the introduction of molecular diversity at all positions on the indole scaffold. The procedure was shown to be successful with a range of both C and N substituents on the o-aminostyrenes. The reaction sequence was tolerant to the reactivity range of alkyllithiums such as tert-, sec-, and n-butyllithium. The electrophiles used were DMF, which generated indole products with C-2 unsubstituted, and nitriles, which incorporated the nitrile substituent at C-2. The o-aminostyrene starting materials were generated by a Pd-catalyzed cross-coupling reaction of a vinyl boronic acid equivalent with the readily available substituted o-bromoanilines.
- Kessler, Albane,Coleman, Claire M.,Charoenying, Patchanee,O'Shea, Donal F.
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p. 7836 - 7846
(2007/10/03)
-
- Hydrosilylation of (hetero)aromatic aldimines in the presence of a Pd(I) complex
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The reaction of triethylsilane with heterocyclic and aromatic azomethines, catalyzed by the [Pd(allyl)Cl]2 complex, was studied. It was found that the reaction is affected by the nature of the functional groups in the aza and methine parts of the aldimine molecules, which were produced by the condensation of furan, thiophene, and benzene aldehydes with aniline and its derivatives. The reactivity of a series of imines is compared with their electronic and structural characteristics, determined by quantum-chemical methods. The corresponding furan, thiophene, and aromatic amines and also certain silylamines were synthesized.
- Iovel,Golomba,Fleisher,Popelis,Grinberga,Lukevics
-
p. 701 - 714
(2007/10/03)
-
- Synthesis of N-Benzylated Anilines from the Reaction of Anilines and Benzyl Chloroformate
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Reactions of benzyl chloroformate with a series of substituted anilines produced N-carbobenzyloxy "CBZ" products along with the unexpected N-benzylated "Bn" compounds. Reaction of aniline, 1a, gave the CBZ, or 2a, and Bn, or 3a, products in 29% and 14% yi
- Pati, Hari,Weisbruch, Paul,Lemon, Adrienne,Lee, Moses
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p. 933 - 940
(2007/10/03)
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- Intramolecular Pd-mediated processes of amino-tethered aryl halides and ketones: Insight into the ketone α-arylation and carbonyl-addition dichotomy. A new class of four-membered azapalladacycles
-
An exploration of the scope and limitations of Pd(O)-catalyzed intramolecular coupling reactions of amino-tethered aryl halides and ketones has been conducted. Two different and competitive reaction pathways starting from ω-(2-haloanilino) alkanones, enolate arylation and addition to the carbonyl group, have been observed, while ω-(2-halobenzylamino) alkanones exclusively underwent the enolate arylation process. The dichotomy between ketone α-arylation and carbonyl-addition in the reactions of ω-(2-haloanilino) alkanones has been rationalized by the intermediacy of unprecedented four-membered azapalladacycles, from which X-ray data and chemical behavior are reported.
- Sole, Daniel,Vallverdu, Lluis,Solans, Xavier,Font-Bardia, Merce,Bonjoch, Josep
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p. 1587 - 1594
(2007/10/03)
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- A novel catalytic one-pot synthesis of carbazoles via consecutive amination and C-H activation
-
Sequential palladium catalysed amination and C-H activation reactions occur between 2-chloro-N-alkylated anilines and aryl bromides to give carbazoles in one pot.
- Bedford, Robin B.,Cazin, Catherine S. J.
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p. 2310 - 2311
(2007/10/03)
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- Palladium-catalysed intramolecular annulation of 2-haloanilines and ketones: Enolate arylation vs. nucleophilic addition to the carbonyl group
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Two alternative annulation pathways involving either the enolate arylation or the addition to the ketone carbonyl group can operate in the Pd-catalysed intramolecular coupling of 2-haloanilines and ketones.
- Sole,Vallverdu,Peidro,Bonjoch
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p. 1888 - 1889
(2007/10/03)
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- Butyltriphenylphosphonium tetraborate (BTPPTB) as a selective reducing agent for the reduction of imines, enamines and oximes and reductive alkylation of aldehydes or ketones with primary amines in methanol or under solid-phase conditions
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Butyltriphenylphosphonium tetraborate (BTPPTB) 1, generated as white solid from butyltriphenylphosphonium bromide and sodium borohydride, is found to be a selective and versatile reducing agent. The reagent in methanol or under solvent-free conditions is very useful for the reduction of imines, enamines and oximes or reductive amination of aldehydes and ketones. Under solvent-free conditions the reactions are faster and the yields of the products are higher.
- Hajipour,Mohammadpoor-Baltork,Noroallhi
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p. 152 - 156
(2007/10/03)
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- Benzytriphenylphosphonium borohydride (BTPPB) as a selective reducing agent for reduction of imines, enamines, and reductive amination of aldehydes with primary and secondry amines in methanol
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Benzyltriphenyltriphenylphosphonium borohydride (BTPPB) (1) generated as white solid from benzyltriphenylphosphonium chloride and sodium borohydride is found to be a selective and versatile reducing agent. The reagent in methanol is very useful for reduction of imines, enamines and reductive animation of aldehydes.
- Hajipour,Mallakpour,Najafi
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p. 197 - 203
(2007/10/03)
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- Synthesis of functionalized pyrrole and indole derivatives through carbometallation of lithiated double bonds
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Bis(2-lithioallyl)amines derived from bis(2-bromoallyl)amines undergo intramolecular carbometallation of a lithiated double bond, giving dilithiated dihydropyrroles. The cyclizations are promoted by N,N,N′,N′-tetramethylethylenediamine (TMEDA). Reaction of these intermediates with electrophiles allows the preparation of some new fused and nonfused five-membered functionalized heterocycles. Although 2-lithioallylamines do not suffer intermolecular carbometallation, dimerization products are obtained with their copper or zirconium derivatives. Finally, the application of this new reaction to 2-lithio-N-(2-lithioallyl)anilines leads to 3-lithiomethylindole derivatives, which are transformed to functionalized indole derivatives by reaction with electrophiles.
- Fananas, Francisco J.,Granados, Alejandro,Sanz, Roberto,Ignacio, Jose M.,Barluenga, Jose
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p. 2896 - 2907
(2007/10/03)
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- 1-Benzyl-1-azonia-4-azabicyclo[2.2.2]octane tetrahydroborate (BAAOTB) as a selective reducing agent
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1-Benzyl-1-azonia-4-azabicyclo[2.2.2]octane tetrahydroborate (BAAOTB) 1 generated as white solid from commercially available DABCO and sodium borohydride is found to be a selective and versatile reducing agent. The reagent in t-butanol is very useful for reduction of imines, enamines, oximes, reductive amination of aldehydes and ketones and reductive methylation of amines.
- Hajipour,Mohammadpoor-Baltork,Rahi
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p. 239 - 242
(2007/10/03)
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- A convenient synthetic route to spiro[indole-3,4'-piperidin]-2-ones
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Starting from 1-[(tert-butoxy)carbonyl]piperidine-4-carboxylic acid and 2-bromoaniline, the spiro[indole-3,4'-piperidin]-2-one system was obtained in three high-yielding steps: anilide formation, N(1)-protection, and intramolecular cyclization under Pd catalysis as the key reaction. The preparation of the corresponding 2-bromoanilide was studied. In extension, the same sequence was developed with 4-methyl- and 4-nitro-2-bromoaniline. In the key step, the NO2 group led to a rather diminished yield. The transformation of the protected spiro[indole-3,4'-piperidin]-2'one to the corresponding unprotected dihydroindoles is discussed.
- Freund, Ralf,Mederski, Werner W. K. R.
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p. 1247 - 1255
(2007/10/03)
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- Halo-substituted aminobenzenes prepared by Pd-catalyzed amination
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The selective monoamination of aryl dihalides by primary amines and polyamines in the presence of the Pd2(dba)3/dppf catalytic system and NaOt- Bu provides a convenient method for the synthesis of aminobenzenes substituted at the ortho, meta, or para position of the aryl ring by a halogen atom. Under these conditions the reaction of polyamine compounds having 1,2-diaminoethane or 1,3-diaminopropane moieties proceeds selectively leading to monoaryl-substituted derivatives of polyamines. Moreover, this is a remarkably efficient method to realize the arylation of a primary amine group of polyamines in the presence of a secondary one.
- Beletskaya, Irina P.,Bessmertnykh, Alla G.,Guilard, Roger
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p. 1459 - 1461
(2007/10/03)
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- The Photochemical Reactions of the Halogenated N-Benzylanilines. Mechanism of the Reactions
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Several N-(2-halobenzyl)anilines and N-benzyl-2-haloanilines have been synthesized and their photochemical reactions studied.Upon irradiation, the aqueous acetonitrile solution of N-benzyl-2-chloroaniline was cyclized and reduced to give phenanthridine, 5,5',6,6'-tetrahydro-6,6'-biphenanthridyl (THBP), N-benzylaniline, and bibenzyl.Similar products were produced in the photochemical reactions of other halogenated N-benzylanilines, except iodo-substituted N-benzylanilines.No dimer (THBP) was produced from the iodo-substituted N-benzylanilines.Both singlet and triplet states are involved in the photochemical reactions of the haloarenes.
- Park, Yong-Tae,Lee, Ick-Hyung,Kim, Young-Hee
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p. 1625 - 1630
(2007/10/02)
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- Synthesis of polysubstituted indoles and indolines by means of zirconocene-stabilized benzyne complexes
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The development of a new method for the regiospecific synthesis of polysubstituted indoles and indolines is reported. The key steps involve the generation of zirconocene-stabilized benzyne complexes and subsequent intramolecular olefin insertion reactions to provide tricyclic indoline zirconacycles. The zirconacyclic intermediates were cleaved with iodine to yield diiodo indolines, which were converted to a wide variety of indole and indoline products, such as analogs of tryptamine, serotonin, tryptophan, and the pharmacophore of CC-1065.
- Tidwell, Jeffrey H.,Buchwald, Stephen L.
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p. 11797 - 11810
(2007/10/02)
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- Electrocatalytic Coupling of Aryl Halides with (1,2-Bis(di-2-propylphosphino)benzene)nickel(0)
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Dibromo- and dichloro(1,2-bis(di-2-propylphosphino)benzene)nickel(II) is compared with tetrakis(triphenylphosphino)nickel(II) as an electrocatalyst for the reductive coupling of aryl halides.In many of the reactions examined, dehalogenation of the substrate predominated over coupling; however, preparative yields of biphenyls as high as 96percent can be obtained with aryl chlorides and 2 mol percent of the title catalyst in polar, coordinating solvents.Experimental factors governing the efficiency of these reactions are discussed, and possible mechanisms for coupling and catalyst deactivation are considered.Much better selectivity for aryl chlorides is attained in electroreductive couplings catalyzed by the title compound, whereas electrocatalysis with (Ph3P)4NiCl2 allows for selective intra- and intermolecular coupling at aryl bromide and vinyl chloride sites.Modest yields of cyclization products can be attained with either electrocatalyst in the presence of appropriately functionalized aryl or vinyl halides.
- Fox, Marye Anne,Chandler, Daniel A.,Lee, Changjin
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p. 3246 - 3255
(2007/10/02)
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