- BF3·Et2O as a metal-free catalyst for direct reductive amination of aldehydes with amines using formic acid as a reductant
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A versatile metal- and base-free direct reductive amination of aldehydes with amines using formic acid as a reductant under the catalysis of inexpensive BF3·Et2O has been developed. A wide range of primary and secondary amines and diversely substituted aldehydes are compatible with this transformation, allowing facile access to various secondary and tertiary amines in high yields with wide functional group tolerance. Moreover, the method is convenient for the late-stage functionalization of bioactive compounds and preparation of commercialized drug molecules and biologically relevant N-heterocycles. The procedure has the advantages of simple operation and workup and easy scale-up, and does not require dry conditions, an inert atmosphere or a water scavenger. Mechanistic studies reveal the involvement of imine activation by BF3and hydride transfer from formic acid.
- Fan, Qing-Hua,Liu, Xintong,Luo, Zhenli,Pan, Yixiao,Xu, Lijin,Yang, Ji,Yao, Zhen,Zhang, Xin
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supporting information
p. 5205 - 5211
(2021/07/29)
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- DIACYLGLYCEROL KINASE MODULATING COMPOUNDS
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The present disclosure provides diacylglycerol kinase modulating compounds, and pharmaceutical compositions thereof, for treating cancer, including solid tumors, and viral infections, such as HIV or hepatitis B virus infection. The compounds can be used alone or in combination with other agents.
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Paragraph 1181
(2021/07/02)
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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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- 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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- Catalytic Selective Oxidative Coupling of Secondary N-Alkylanilines: An Approach to Azoxyarene
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Azoxyarenes are among important scaffolds in organic molecules. Direct oxidative coupling of primary anilines provides a concise fashion to construct them. However, whether these scaffolds can be prepared from secondary N-alkylanilines is not well explored. Here, we present a catalytic selective oxidative coupling of secondary N-alkylaniline to afford azoxyarene with tungsten catalyst under mild conditions. In addition, azoxy can be viewed as a bioisostere of alkene and amide. Several "azoxyarene analogues" of the corresponding bioactive alkenes and amides showed comparable promising anticancer activities.
- Ke, Lei,Zhu, Guirong,Qian, Hui,Xiang, Guangya,Chen, Qin,Chen, Zhilong
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supporting information
p. 4008 - 4013
(2019/06/04)
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- Borrowing Hydrogen-Mediated N-Alkylation Reactions by a Well-Defined Homogeneous Nickel Catalyst
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We report herein a well-defined and bench-stable azo-phenolate ligand-coordinated nickel catalyst which can efficiently execute N-alkylation of a variety of anilines by alcohol. We demonstrate that the redox-active azo ligand can store hydrogen generated during alcohol oxidation and redelivers the same to an in-situ-generated imine bond to result in N-alkylation of amines. The reaction has wide scope, and a large array of alcohols can directly couple to a variety of anilines. Mechanistic studies including deuterium labeling to the substrate establishes the borrowing hydrogen method from alcohols and pinpoints the crucial role of the redox-active azo moiety present on the ligand backbone. Isolation of the ketyl intermediate in its trapped form with a radical quencher and higher kH/kD for the alcohol oxidation step suggest altogether a hydrogen-atom transfer (HAT) to the reduced azo backbone to pave alcohol oxidation as opposed to the conventional metal-ligand bifunctional mechanism. This example clearly demonstrates that an inexpensive base metal catalyst can accomplish an important coupling reaction with the help of a redox-active ligand backbone.
- Bains, Amreen K.,Kundu, Abhishek,Yadav, Sudha,Adhikari, Debashis
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p. 9051 - 9059
(2019/10/02)
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- Reductive Amination by Photoredox Catalysis and Polarity-Matched Hydrogen Atom Transfer
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The excitation of a RuII photosensitizer in the presence of ascorbic acid leads to the reduction of iminium ions to electron-rich α-aminoalkyl radical intermediates, which are rapidly converted into reductive amination products by thiol-mediated hydrogen atom transfer (HAT). As a result, the reductive amination of carbonyl compounds with amines by photoredox catalysis proceeds in good to excellent yields and with broad substrate scope and good functional group tolerance. The three key features of this work are 1) the rapid interception of electron-rich α-aminoalkyl radical intermediates by polarity-matched HAT in a photoredox reaction, 2) the method of reductive amination by photoredox catalysis itself, and 3) the application of this new method for temporally and spatially controlled reactions on a solid support, as demonstrated by the attachment of a fluorescent dye on an activated cellulose support by photoredox-catalyzed reductive amination.
- Guo, Xingwei,Wenger, Oliver S.
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supporting information
p. 2469 - 2473
(2018/01/27)
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- Unusual 1,1-Hydroboration Route to a Reactive Unsaturated Vicinal Frustrated Phosphane/Borane Lewis Pair
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Piers' borane HB(C6F5)2 reacted with the alkyne Mes2P-C≡ ≡C-SiMe3 by a rarely observed 1,1-hydroboration reaction under kinetic control to give the unsaturated vicinal frustrated phosphane/borane Lewis pair 6, featuring both the PMes2 and SiMe3 groups at the same carbon atom C1. Compound 6 is a reactive P/B FLP which splits dihydrogen under mild conditions. Thermolysis at 100 °C converts it to the markedly less reactive P/B FLP regioisomer which bears the -SiMe3 substituent at carbon atom C2 adjacent to the B(C6F5)2 group. Most new compounds were characterized by X-ray diffraction.
- Ueno, Atsushi,Tao, Xin,Daniliuc, Constantin G.,Kehr, Gerald,Erker, Gerhard
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supporting information
p. 2665 - 2668
(2018/09/10)
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- Efficient Ruthenium(II)-Catalyzed Direct Reductive Amination of Aldehydes under Mild Conditions Using Hydrosilane as the Reductant
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A direct reductive amination of aldehydes with anilines is performed with a ruthenium(II)-(arene) catalyst. The [RuCl2(p-cymene)]2/Ph2SiH2 catalytic system is very efficient for the synthesis of secondary amines and tertiary amines in good yields, and is highly chemoselective, tolerating a wide range of functional groups, such as NO2, CN, CO2Me, F, Cl, Br, OMe, Me, furyl and alkyl. We also report an interesting direductive amination of 2-ethylbutanal.
- Li, Bin,Zheng, Jianxiong,Zeng, Weifeng,Li, Yibiao,Chen, Lu
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supporting information
p. 1349 - 1355
(2017/03/11)
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- Imidazolium-based ionic liquid-catalyzed hydrosilylation of imines and reductive amination of aldehydes using hydrosilane as the reductant
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The first imidazolium-based ionic liquid-catalyzed hydrosilylation of imine and reductive amination of aldehydes with primary amines using a catalytic amount of 1-butyl-3-methylimidazolium tetrachloride iron [BMIm][FeCl4] and Ph2SiH2 as a reductant were performed under mild conditions. Good yields of secondary amines with high chemoselectivity and a tolerance for a wide range of functional groups were obtained.
- Li, Bin,Zhang, Shilin,Wu, Weizhen,Liang, Lecheng,Jiang, Shaohua,Chen, Lu,Li, Yibiao
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p. 31795 - 31799
(2017/07/10)
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- Direct catalytic N-alkylation of amines with carboxylic acids
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A straightforward process for the N-alkylation of amines has been developed applying readily available carboxylic acids and silanes as the hydride source. Complementary to known reductive aminations, effective C-N bond construction proceeds under mild conditions and allows obtaining a broad range of alkylated secondary and tertiary amines, including fluoroalkyl-substituted anilines as well as the bioactive compound Cinacalcet HCl.
- Sorribes, Iván,Junge, Kathrin,Beller, Matthias
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p. 14314 - 14319
(2014/12/10)
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- Selective N-alkylation of amines using nitriles under hydrogenation conditions: Facile synthesis of secondary and tertiary amines
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Nitriles were found to be highly effective alkylating reagents for the selective N-alkylation of amines under catalytic hydrogenation conditions. For the aromatic primary amines, the corresponding secondary amines were selectively obtained under Pd/C-catalyzed hydrogenation conditions. Although the use of electron poor aromatic amines or bulky nitriles showed a lower reactivity toward the reductive alkylation, the addition of NH4OAc enhanced the reactivity to give secondary aromatic amines in good to excellent yields. Under the same reaction conditions, aromatic nitro compounds instead of the aromatic primary amines could be directly transformed into secondary amines via a domino reaction involving the one-pot hydrogenation of the nitro group and the reductive alkylation of the amines. While aliphatic amines were effectively converted to the corresponding tertiary amines under Pd/C-catalyzed conditions, Rh/C was a highly effective catalyst for the N-monoalkylation of aliphatic primary amines without over-alkylation to the tertiary amines. Furthermore, the combination of the Rh/C-catalyzed N-monoalkylation of the aliphatic primary amines and additional Pd/C-catalyzed alkylation of the resulting secondary aliphatic amines could selectively prepare aliphatic tertiary amines possessing three different alkyl groups. According to the mechanistic studies, it seems reasonable to conclude that nitriles were reduced to aldimines before the nucleophilic attack of the amine during the first step of the reaction.
- Ikawa, Takashi,Fujita, Yuki,Mizusaki, Tomoteru,Betsuin, Sae,Takamatsu, Haruki,Maegawa, Tomohiro,Monguchi, Yasunari,Sajiki, Hironao
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supporting information; experimental part
p. 293 - 304
(2012/02/01)
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- One-pot synthesis of aniline derivatives from nitroarenes under mild conditions promoted by a recyclable polymer-supported palladium catalyst
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This work describes the one-pot direct reductive amination of carbonyl compounds with nitroarenes promoted by a polymer supported palladium catalyst, in the presence of molecular hydrogen as the reductant. This methodology is applicable, with slight differences, to both aliphatic and aromatic aldehydes. The operational simplicity, the mild reaction conditions, the high yields and the good recyclability of the supported catalyst are major advantages of this method. TEM observations of the catalyst showed that the active species are palladium nanoparticles having a size distribution centered at 5 nm within the polymeric support.
- Dell'Anna, Maria Michela,Mastrorilli, Piero,Rizzuti, Antonino,Leonelli, Cristina
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scheme or table
p. 134 - 140
(2012/03/27)
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- Ultrathin platinum nanowire catalysts for direct C-N coupling of carbonyls with aromatic nitro compounds under 1 bar of hydrogen
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Traditionally important in the pharmaceutical, agrochemical, and synthetic dye industries, C-N coupling has proved useful for the preparation of a number of valuable organic compounds. Here, a new method for the direct one-pot reductive C-N coupling from carbonyl and aromatic nitro compounds is described. Employing ultrathin platinum nanowires as the catalyst and hydrogen as the reducing agent, N-alkylamines were achieved in high yields. Debenzylation products were not detected after prolonged reaction times. Time-dependent analysis, ReactIR spectroscopy and DFT calculations revealed that the C-N coupling proceeded through a different mechanism than traditional "reductive amination." N-Alkylamines were directly obtained by intermolecular dehydration over platinum nanowires under a hydrogen atmosphere, instead of intramolecular water elimination and imine hydrogenation.
- Hu, Lei,Cao, Xueqin,Ge, Danhua,Hong, Haiyan,Guo, Zhiqiang,Chen, Liang,Sun, Xuhui,Tang, Jianxin,Zheng, Junwei,Lu, Jianmei,Gu, Hongwei
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experimental part
p. 14283 - 14287
(2012/01/06)
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- Regioselective synthesis of heterocycles containing nitrogen neighboring an aromatic ring by reductive ring expansion using diisobutylaluminum hydride and studies on the reaction mechanism
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(Chemical Equation Presented) A systematic investigation of the reductive ring-expansion reaction of cyclic ketoximes fused to aromatic ringswith diisobutylaluminum hydride (DIBALH) is described. This reaction regioselectively afforded a variety of five- to eight-membered bicyclic heterocycles or tricyclic heterocycles containing nitrogen neighboring an aromatic ring, including indoline, 1,2,3,4,5,6-hexahydrobenz[b]azocine, 3,4-dihydro-2H-benzo[b] [1,4]oxazine, 2,3,4,5-tetrahydrobenzo[b][1,4]thiazepine, 1,2,3,4,5,6- hexahydroazepino[3,2-b]-indole, 2,3,4,5-tetrahydro-1H-benzothieno[2,3-b]azepine, 2,3,4,5-tetrahydro-1H-benzothieno[3,2-b]-azepine, 5,6-dihydrophenanthridine, and 5,6,11,12-tetrahydrodibenz[b, f]azocine. The reaction mechanism leading to the rearrangement was investigated on the basis of the restricted Becke three-parameter plus Lee-Yang-Parr (B3LYP) density functional theory (DFT) with the 6-31G (d) basis set. It was found that the reaction proceeds through a three-centered transition state via a stepwise mechanism because the potential energy curve along the intrinsic reaction coordinate (IRC) had twomaxima (saddle points; TS1 and TS2) and the partial phenonium cation intermediate C. In addition to cyclic ketoximes fused to aromatic rings, the reactions of various cyclic and acyclic ketoximeswere examined to investigate preference of migrating group. It was found that themore electron-rich group migrated preferentially to give the corresponding secondary amines.
- Cho, Hidetsura,Iwama, Yusuke,Sugimoto, Kenji,Mori, Seiji,Tokuyama, Hidetoshi
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experimental part
p. 627 - 636
(2010/04/29)
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- Direct reductive amination and selective 1,2-reduction of α,β-unsaturated aldehydes and ketones by NaBH4 using H3PW12O40 as catalyst
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A simple and convenient procedure for direct reductive amination of aldehydes and ketones with sodium borohydride is described. The reaction has been carried out in methanol in the presence of a catalytic amount of H3PW12O40 (0.5 mol %). α,β-Unsaturated aldehydes and ketones can be easily converted into the corresponding allyl alcohols by reaction with H3PW12O40 (0.5 mol %)/NaBH4.
- Heydari, Akbar,Khaksar, Samad,Akbari, Jafar,Esfandyari, Maryam,Pourayoubi, Mehrdad,Tajbakhsh, Mahmoud
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p. 1135 - 1138
(2007/10/03)
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- One-pot reductive mono-N-alkylation of aniline and nitroarene derivatives using aldehydes
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(Chemical Equation Presented) One-pot reductive mono-N-alkylation of aniline and nitroarene derivatives using various aldehydes by Pd/C catalyst in aqueous 2-propanol solvent with ammonium formate as in situ hydrogen donor is illustrated. The reaction proceeded smoothly and selectively with excellent yield at room temperature. Our protocol presents a facile, economical, and environmentally benign alternative for reductive amination.
- Byun, Eunyoung,Hong, Bomi,De Castro, Kathlia A.,Lim, Minkyung,Rhee, Hakjune
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p. 9815 - 9817
(2008/03/27)
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- Substituted 4-hydroxyphenyl sulfonamides as pathway-selective estrogen receptor ligands
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The transcription factor nuclear factor-κB (NF-κB) is a key component in the onset of inflammation. We describe here a series of 4-hydroxyphenyl sulfonamide estrogen receptor (ER) ligands that selectively inhibit NK-κB transcriptional activity but are devoid of conventional estrogenic activity.
- Sabatucci, Joseph P.,Ashwell, Mark A.,Trybulski, Eugene,O'Donnell, Mary-Margaret,Moore, William J.,Harnish, Douglas C.,Chadwick, Christopher C.
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p. 854 - 858
(2007/10/03)
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- Preparation of tri- and difluoromethylated amines from aldimines using (trifluoromethyl)trimethylsilane
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Addition of a trifluoromethyl group into aldimines was accomplished using (trifluoromethyl)trimethylsilane with tetraalkylammonium fluorides as initiators, and the resulting adducts were converted to difluoromethylated imines in the presence of excess flu
- Surya Prakash,Mogi, Ryo,Olah, George A.
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p. 3589 - 3592
(2007/10/03)
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- A general one-pot, three-component mono N-alkylation of amines and amine derivatives in lithium perchlorate/diethyl ether solution
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An efficient, general procedure for reductive monoalkylation of amines and amine derivatives with aldehydes is reported. Treatment of aldehydes with primary amines, secondary amines, O-trimethylsilylhydroxylamine, and N,N-dimethylhydrazine in lithium perc
- Heydari, Akbar,Tavakol, Hossein,Aslanzadeh, Saied,Azarnia, Jamshid,Ahmadi, Nafiseh
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p. 627 - 633
(2007/10/03)
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- Reductive and catalytic monoalkylation of primary amines using nitriles as an alkylating reagent
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(Chemical Equation Presented) A selective and catalytic mono-N-alkylation method of both aromatic and aliphatic amines using nitriles as an alkylating agent with Pd/C or Rh/C as a catalyst is described. This method is particularly attractive to provide an environmentally benign and applicable alkylation method of amines without using toxic and corrosive alkylating agents such as alkyl halides and carbonyl compounds.
- Sajiki, Hironao,Ikawa, Takashi,Hirota, Kosaku
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p. 4977 - 4980
(2007/10/03)
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- Solvent-free one-pot reduction of imines generated in situ from aldehydes and aniline by tributyltin hydride on silica gel
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Imines generated in situ from aldehydes and aniline can be reduced using tributyltin hydride on silica gel under solvent-free conditions to provide the corresponding amines in good yields.
- Hiroi, Ryoichi,Miyoshi, Norikazu,Wada, Makoto
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p. 274 - 275
(2007/10/03)
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- Synthesis and structures of lithium N-trimethylsilyl- and -neopentyl-anilides and their Et2O and tmen adducts; Crystal structures of [(Li{μ-N(Ph)R}-trans)2(μ-tmen)]∞ (R = SiMe3 1 or CH2But 2) and [Li{μ-N(Ph)CH2But}(OEt2)]2
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The synthesis and structures of lithium N-trimethylsilyl- and -neopentyl-anilides and their Et2O and tmen adducts were studied by using nuclear magnetic resonance (NMR) spectroscopy. The treatment of N-trimethylsilyl- or -neopentyl-aniline successively with n-butyllithium and tmen in hexane yielded the crystalline polymeric lithium amides. The results showed that the reactivity of lithium amides was related to their degree of aggregation because the high polarity of the Li-N bond caused it to associate in the absence of a neutral donor.
- Bezombes, Jean Philippe,Hitchcock, Peter B.,Lappert, Michael F.,Merle, Philippe G.
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p. 816 - 821
(2007/10/03)
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- Bimolecular Nucleophilic Substitution (SN2) Reactions of Neopentyl Arenesulfonates with Anilines and Benzylamines in Methanol
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Bimolecular nucleophilic substitution (SN2) reactions of neopentyl arenesulfonates with anilines and benzylamines in methanol at 55.0 deg C are reported.The tightness of the transition state (TS) is similar to that for other typical SN2 processes at a primary alkyl carbon centre based on the magnitude of the cross-interaction constant ρxz (0.30) between the substituents in the nucleophile (X) and leaving group (Z).The TS variation is in accord with that predicted by the potential energy surface diagram, which in turn is consistent with the positive sign of ρxz; a later TS is obtained with a weaker nucleophile and nucleofuge.Taft's polar substituent constant, ?*, for the trimethylsilyl group is estimated to be -0.48 by using a factor of 1.875 for the fall-off of ?* from the tert-butyl to the neopentyl group and extrapolating from the experimental Taft plot.
- Koh, Han Joong,Lee, Hai Whang,Lee, Ikchoon
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p. 253 - 258
(2007/10/02)
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- Synthesis of Amines via Carbon-Sulfur Bond Cleavages of Substituted Aminomethyl Sulfides with Organolithium Reagents: Aminocarbene Route to Enamines and Sterically Hindered Amines
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N-Substituted and N,N-disubstituted aminomethyl sulfides can be converted into secondary and tertiary amines, respectively, by organolithium reagents in high yields, regardless of whether the N-substituent is alkyl or aryl; for the former case, imines, and for the latter case, aminocarbenes, are the most likely intermediates.
- Eisch, John J.,McNulty, John F.,Shi, Xian
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- A HIGHLY EFFICIENT AND GENERAL N-MONOMETHYLATION OF FUNCTIONALIZED PRIMARY AMINES VIA FORMYLATION -- BORANE:METHYL SULFIDE REDUCTION
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Formylation of functionalized primary aromatic and aliphatic amines with acetic formic anhydride (AFA) followed by borane:methyl sulfide reduction in the same pot affords the corresponding N-methylamines in excellent isolated yields, uncontaminated by bis alkylation; the reaction sequence is applicable to even very weakly basic and sterically hindered amines.
- Krishnamurthy, S.
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p. 3315 - 3318
(2007/10/02)
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