- Deoxygenative hydroboration of primary, secondary, and tertiary amides: Catalyst-free synthesis of various substituted amines
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Transformation of relatively less reactive functional groups under catalyst-free conditions is an interesting aspect and requires a typical protocol. Herein, we report the synthesis of various primary, secondary, and tertiary amines through hydroboration of amides using pinacolborane under catalyst-free and solvent-free conditions. The deoxygenative hydroboration of primary and secondary amides proceeded with excellent conversions. The comparatively less reactive tertiary amides were also converted to the corresponding N,N-diamines in moderate yields under catalyst-free conditions, although alcohols were obtained as a minor product.
- Yi, Jaeeun,Kim, Hyun Tae,Jaladi, Ashok Kumar,An, Duk Keun
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supporting information
p. 129 - 132
(2021/11/17)
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- Mild and Selective Rhodium-Catalyzed Transfer Hydrogenation of Functionalized Arenes
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Diboron-mediated rhodium-catalyzed transfer hydrogenation of functionalized arenes is reported. In addition to good functional group tolerance, the reaction features operational simplicity and controllable chemoselectivity. The general applicability of this procedure is demonstrated by the selective hydrogenation of a range of arenes, including functionalized benzenes, biphenyls, and polyaromatics.
- Wang, Yuhan,Chang, Zhiqian,Hu, Yan,Lin, Xiao,Dou, Xiaowei
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supporting information
p. 1910 - 1914
(2021/03/08)
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- Deconstructing Noncovalent Kelch-like ECH-Associated Protein 1 (Keap1) Inhibitors into Fragments to Reconstruct New Potent Compounds
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Targeting the protein-protein interaction (PPI) between nuclear factor erythroid 2-related factor 2 (Nrf2) and Kelch-like ECH-associated protein 1 (Keap1) is a potential therapeutic strategy to control diseases involving oxidative stress. Here, six classes of known small-molecule Keap1-Nrf2 PPI inhibitors were dissected into 77 fragments in a fragment-based deconstruction reconstruction (FBDR) study and tested in four orthogonal assays. This gave 17 fragment hits of which six were shown by X-ray crystallography to bind in the Keap1 Kelch binding pocket. Two hits were merged into compound 8 with a 220-380-fold stronger affinity (Ki = 16 μM) relative to the parent fragments. Systematic optimization resulted in several novel analogues with Ki values of 0.04-0.5 μM, binding modes determined by X-ray crystallography, and enhanced microsomal stability. This demonstrates how FBDR can be used to find new fragment hits, elucidate important ligand-protein interactions, and identify new potent inhibitors of the Keap1-Nrf2 PPI.
- Pallesen, Jakob S.,Narayanan, Dilip,Tran, Kim T.,Solbak, Sara M. ?.,Marseglia, Giuseppe,S?rensen, Louis M. E.,H?j, Lars J.,Munafò, Federico,Carmona, Rosa M. C.,Garcia, Anthony D.,Desu, Haritha L.,Brambilla, Roberta,Johansen, Tommy N.,Popowicz, Grzegorz M.,Sattler, Michael,Gajhede, Michael,Bach, Anders
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p. 4623 - 4661
(2021/05/07)
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- Amine-boranes as Dual-Purpose Reagents for Direct Amidation of Carboxylic Acids
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Amine-boranes serve as dual-purpose reagents for direct amidation, activating aliphatic and aromatic carboxylic acids and, subsequently, delivering amines to provide the corresponding amides in up to 99% yields. Delivery of gaseous or low-boiling amines as their borane complexes provides a major advantage over existing methodologies. Utilizing amine-boranes containing borane incompatible functionalities allows for the preparation of functionalized amides. An intermolecular mechanism proceeding through a triacyloxyborane-amine complex is proposed.
- Choudhary, Shivani,Hamann, Henry J.,Ramachandran, P. Veeraraghavan
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supporting information
(2020/11/13)
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- A scalable continuous photochemical process for the generation of aminopropylsulfones
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An efficient continuous photochemical process is presented that delivers a series of novel γ-aminopropylsulfones via a tetrabutylammonium decatungstate (TBADT) catalysed HAT-process. Crucial to this success is the exploitation of a new high-power LED emitting at 365 nm that was found to be superior to an alternative medium-pressure Hg lamp. The resulting flow process enabled the scale-up of this transformation reaching throughputs of 20 mmol h-1 at substrate concentrations up to 500 mM. Additionally, the substrate scope of this transformation was evaluated demonstrating the straightforward incorporation of different amine substituents as well as alkyl appendages next to the sulfone moiety. It is anticipated that this methodology will allow for further exploitations of these underrepresented γ-aminopropylsulfone scaffolds in the future. This journal is
- Baumann, Marcus,Bonciolini, Stefano,Di Filippo, Mara
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supporting information
p. 9428 - 9432
(2020/12/15)
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- Cobalt-Nanoparticles Catalyzed Efficient and Selective Hydrogenation of Aromatic Hydrocarbons
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The development of inexpensive and practical catalysts for arene hydrogenations is key for future valorizations of this general feedstock. Here, we report the development of cobalt nanoparticles supported on silica as selective and general catalysts for such reactions. The specific nanoparticles were prepared by assembling cobalt-pyromellitic acid-piperazine coordination polymer on commercial silica and subsequent pyrolysis. Applying the optimal nanocatalyst, industrial bulk, substituted, and functionalized arenes as well as polycyclic aromatic hydrocarbons are selectively hydrogenated to obtain cyclohexane-based compounds under industrially viable and scalable conditions. The applicability of this hydrogenation methodology is presented for the storage of H2 in liquid organic hydrogen carriers.
- Murugesan, Kathiravan,Senthamarai, Thirusangumurugan,Alshammari, Ahmad S.,Altamimi, Rashid M.,Kreyenschulte, Carsten,Pohl, Marga-Martina,Lund, Henrik,Jagadeesh, Rajenahally V.,Beller, Matthias
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p. 8581 - 8591
(2019/09/12)
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- Iridium-Catalyzed Reductive Strecker Reaction for Late-Stage Amide and Lactam Cyanation
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A new iridium-catalyzed reductive Strecker reaction for the direct and efficient formation of α-amino nitrile products from a broad range of (hetero)aromatic and aliphatic tertiary amides, and N-alkyl lactams is reported. The protocol exploits the mild and highly chemoselective reduction of the amide and lactam functionalities using IrCl(CO)[P(C6H5)3]2 (Vaska's complex) in the presence of tetramethyldisiloxane, as a reductant, to directly generate hemiaminal species able to undergo substitution by cyanide upon treatment with TMSCN (TMS=trimethylsilyl). The protocol is simple to perform, broad in scope, efficient (up to 99 % yield), and has been successfully applied to the late-stage functionalization of amide- and lactam-containing drugs, and naturally occurring alkaloids, as well as for the selective cyanation of the carbonyl carbon atom linked to the N atom of proline residues within di- and tripeptides.
- Fuentes de Arriba, ángel L.,Lenci, Elena,Sonawane, Mahendra,Formery, Odilon,Dixon, Darren J.
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supporting information
p. 3655 - 3659
(2017/03/21)
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- Metal-Free Amidation of Acids with Formamides and T3P
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A new, simple and metal-free method for the direct formation of dialkylamides from carboxylic acids employing N,N-dialkylformamides as amine source is described. The one-pot reaction is promoted by propylphosphonic anhydride (T3P) in the presence of 0.5 equivalents of HCl.
- Bannwart, Linda,Abele, Stefan,Tortoioli, Simone
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p. 2069 - 2078
(2016/07/06)
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- Transition metal nanoparticles stabilized by ammonium salts of hyperbranched polystyrene: effect of metals on catalysis of the biphasic hydrogenation of alkenes and arenes
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Abstract Hyperbranched polystyrene bearing ammonium salts (HPS-NR3+Cl-) behaves as an excellent stabilizer of ruthenium, rhodium, iridium, palladium, and platinum nanoparticles from 1 to 3 nm in size uniformly dispersed in the polymer matrix. The catalytic performance of the resulting metal-polymer composites, M@HPS-NR3+Cl-, is dependent on the metal. This dependence was investigated by assessing the hydrogenation of alkenes and arenes. The utility of M@HPS-NR3+Cl- as reusable catalysts in aqueous/organic biphasic systems was demonstrated by examining the catalysis of the hydrogenation of aromatic compounds containing various functional groups by Ru@HPS-NR3+Cl-.
- Gao, Lei,Kojima, Keisuke,Nagashima, Hideo
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p. 6414 - 6423
(2015/08/18)
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- Bromination of enamines from tertiary amides using the petasis reagent: A convenient one-pot regioselective route to bromomethyl ketones
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An original one-pot synthesis of bromomethyl ketones is achived using the Petasis reagent (dimethyltitanocene) as a key for enamine generation. Several amides were used to test the limits of the procedure by changing either the alkyl chain R or the amino portion of the starting materials. The enamines generated in situ were allowed to react with bromine at low temperature followed by hydrolysis to yield bromomethyl ketones in excellent yields (85 to 95%). Mechanistic details and optimum conditions for the reaction are briefly discussed. The present approach offers several advantages such as regioselectivity in enamine formation, good yields, mild reaction conditions, and ease of experimentation.
- Kobeissi, Marwan,Cherry, Khalil,Jomaa, Wissam
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supporting information
p. 2955 - 2965
(2013/09/02)
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- Pseudomonas stutzeri lipase: A useful biocatalyst for aminolysis reactions
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The use of Pseudomonas stutzeri lipase (PSL) as a biocatalyst for aminolysis reactions with bulky substrates has been investigated. PSL compared favorably to Novozym 435 (immobilized Candida antarctica lipase B, NOV435) in the aminolysis of various bulky methyl esters and amines. While NOV435 demonstrated a higher rate of aminolysis with methyl 2-phenylpropionic acid as the acyl donor, PSL outperformed NOV435 with secondary amines as the nucleophile. Methanol inhibition and a low affinity for bulky acyl donors were found to be the two main reasons for relatively low rates in the PSL-catalyzed aminolysis reactions. It was demonstrated that the use of molsieve 4A had a significant effect on the aminolysis rate and amide yield, since it enabled the effective removal of the inhibiting methanol from the reaction mixture.
- Van Pelt,Teeuwen,Janssen,Sheldon,Dunn,Howard,Kumar,Martinez,Wong
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experimental part
p. 1791 - 1798
(2011/10/09)
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- Selective hydrogenation of amides using ruthenium/ molybdenum catalysts
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Recyclable, heterogeneous bimetallic ruthenium/molybdenum catalysts, formed in situ from triruthenium dodecacarbonyl [Ru3(CO)12] and molybdenum hexacarbonyl [Mo(CO)6], are effective for the selective liquid phase hydrogenation of cyclohexylcarboxamide (CyCONH2) to cyclohexanemethylamine (CyCH2NH2), with no secondary or tertiary amine by-product formation. Variation of Mo:Ru composition reveals both synergistic and poisoning effects, with the optimum combination of conversion and selectivity at ca. 0.5, and total inhibition of catalysis evident at ≥1. Good amide conversions are noted within the reaction condition regimes 20100 bar hydrogen and 145-160°C. The order of reactivity of these catalysts towards reduction of different amide functional groups is primary > tertiary ? secondary. In situ HP-FT-IR spectroscopy confirms that catalyst genesis occurs during an induction period associated with decomposition of the organometallic precursors. Ex situ characterisation, using XRD, XPS and EDX-STEM, for active Mo:Ru compositions, has provided evidence for intimately mixed ca. 2.5-4 nm particles that contain metallic ruthenium, and molybdenum (in several oxidation states, including zero).
- Beamson, Graham,Papworth, Adam J.,Philipps, Charles,Smith, Andrew M.,Whyman, Robin
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experimental part
p. 869 - 883
(2010/07/05)
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- Hydrosilane reduction of tertiary carboxamides by iron carbonyl catalysts
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Fox in the carboxamide: Reduction of tertiary carboxamides to their corresponding amines is catalyzed by [Fe(CO)5] or [Fe 3(CO)12], using 1,1,3,3tetramethyldlsiloxane (TMDS) as the reducing agent. The reaction proceeds under either thermal or photochemical conditions. Unlike the hydrosilane reduction of amides using platinum or ruthenlum catalysts, TMDS preferentially reduces a nitro group, even in the presence of competing amides.
- Sunada, Yusuke,Kawakami, Hiroko,Imaoka, Tsuyoshi,Motoyama, Yukihiro,Nagashima, Hideo
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supporting information; experimental part
p. 9511 - 9514
(2010/03/24)
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- Practical access to amines by platinum-catalyzed reduction of carboxamides with hydrosilanes: Synergy of dual Si-H groups leads to high efficiency and selectivity
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The synergetic effect of two Si-H groups leads to efficient reduction of carboxamides to amines by platinum catalysts under mild conditions. The rate of the reaction is dependent on the distance of two Si-H groups; 1,1,3,3-tetramethyldisiloxane (TMDS) and 1,2-bis(dimethylsilyl)benzene are found to be an effective reducing reagent. The reduction of amides having other reducible functional groups such as NO2, CO2R, CN, CdC, Cl, and Br moieties proceeds with these groups remaining intact, providing a reliable method for the access to functionalized amine derivatives. The platinum-catalyzed reduction of amides with polymethylhydrosiloxane (PMHS) also proceeds under mild conditions. The reaction is accompanied by automatic removal of both platinum and silicon wastes as insoluble silicone resin, and the product is obtained by simple extraction. A mechanism involving double oxidative addition of TMDS to a platinum center is discussed.
- Hanada, Shiori,Tsutsumi, Emi,Motoyama, Yukihiro,Nagashima, Hideo
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supporting information; experimental part
p. 15032 - 15040
(2010/01/29)
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- The extraordinary reactions of phenyldimethylsilyllithium with N,N-disubstituted amides
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The reactions of the silyllithium reagent with tertiary amides was discussed. The enediamines were easily isomerized from cis to trans, easily oxidized to dienediamines and were hydrolyzed to α-aminoketones. If the two equivalents of the silyllithium reagent were used, the product was an α-silylamine. The results show that each member of the homologous series of amides gives rise to a substantially different product.
- Buswell, Marina,Fleming, Ian,Ghosh, Usha,Mack, Stephen,Russell, Matthew,Clark, Barry P.
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p. 3006 - 3017
(2007/10/03)
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- Vinyl-λ3-iodanes act as efficient sulfur atom acceptors: Vinylic SN2-based strategy for conversion of tertiary thioamides to amides
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Exposure of tertiary thioamides to (E)-1-hexenyl(phenyl)-λ3-iodane results in vinylic SN2 reaction to give the inverted (Z)-S-vinylthioimidonium salts, which under alkaline hydrolysis (Na2CO3 or K2CO
- Ochiai, Masahito,Yamamoto, Shinji
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p. 2802 - 2803
(2007/10/03)
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- Direct transacylation of 2,2,2-trihaloethyl esters with amines and alcohols using phosphorus(III) reagents for reductive fragmentation and in situ activation
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Amides and esters have been synthesized from 2,2,2-trihaloethyl esters in one pot using phosphorus(III) reagents as reductants, with resultant carboxylate activation as an acyloxyphosphonium intermediate, and in situ trapping by amine or alcohol nucleophiles. Secondary and tertiary amides were synthesized, including a dipeptide, in good yields using hexamethylphosphorous triamide, (Me2N)3P, as reducing agent. Optimal yields of esters derived from primary and secondary alcohols were obtained using tributylphosphine and DMAP. Tribromoethyl esters provided yields superior to those obtained with trichloroethyl esters.
- Hans, Jeremy J.,Driver, Russell W.,Burke, Steven D.
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p. 2114 - 2121
(2007/10/03)
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- A general and practical method of synthesis of 2-disubstituted-1- chloro- and 1-bromoenamines
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Disubstituted-α-chloroenamines are useful synthetic intermediates which had earlier been prepared by the reaction of tertiary amides with phosgene. The toxicity of the latter led us to systematically investigate new synthetic routes towards α-chloro- and
- Ghosez, Leon,George-Koch, Isabelle,Patiny, Luc,Houtekie, Marc,Bovy, Philippe,Nshimyumukiza, Prosper,Phan, Thao
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p. 9207 - 9222
(2007/10/03)
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- A Novel Series of N-(1-Aminoalkylidene)carboximidamides as Potential Hypoglycemic Agents
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Nitrogen heterocyclic carboximidamides, such as linogliride, 1a, have been shown to possess significant hypoglycemic activity and have shown clinical efficacy as potential antidiabetic agents.We evaluated the biological significance of the heterocyclic ring A of general structure 1, which has always been maintained in this class of compounds, by preparing acyclic compounds of general structure 2.Preliminary in vivo biological testing, i.e., the glucose tolerance test in rats, indicates that a number of the specific acyclic carboximidamides prepared, 6a-6kk, possessed significant hypoglycemic activity often comparable to, and in some cases better than, the activity noted for our model compound, 1a.These results suggest that the heterocyclic ring A of 1 is not essential for hypoglycemic activity for this class of compounds.
- Breslin, Henry J.,Kukla, Michael J.,Tuman, Robert W.,Rebarchak, Mary C.,Bowden, Charles R.
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p. 1597 - 1603
(2007/10/02)
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- Compounds
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Polystyrene polymers of structure : in which, R1 and R2 are the same or different and are each C1 4 alkyl; R3 is (CH2)nR4 in which R4 is C3 6 cycloalkyl or a bicyclic carbocyclic ring of up to 10 carbon atoms and n is 1 to 12, or R3 is (CH2)nCH = R5R6 in which n is 1 to 12 and R5 and R6 together form a C3 6 cycloalkyl ring or a bicyclic carbocyclic ring of up to 10 carbon atoms; R7 is hydrogen or a group CH2N R1R2R3X ; X is a counter ion; a, b and c are numbers which indicate the relative molar percentages of the units present in said polymer, (b) being from about 1 to about 10 molar percent, and (c) being from about 30 to about 98 molar percent; m is a number indicating the degree of polymerisation of said polymer, processes for their preparation, compositions containing them and their use in therapy as bile acid sequestering agents.
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- AN ALTERNATIVE PROCEDURE FOR THE ALUMINUM-MEDIATED CONVERSION OF ESTERS TO AMIDES
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A convenient method has been developed for directly converting esters to amides using reagents derived from the reaction of trimethylaluminum with ammonium chloride, methylamine hydrochloride or dimethylamine hydrochloride.
- Levin, Jeremy I.,Turos, Edward,Weinreb, Steven M.
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p. 989 - 994
(2007/10/02)
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