- B(C6F5)3-catalyzed tandem protonation/deuteration and reduction of: In situ -formed enamines
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A highly efficient B(C6F5)3-catalyzed tandem protonation/deuteration and reduction of in situ-formed enamines in the presence of water and pinacolborane was developed. Regioselective β-deuteration of tertiary amines was achieved with high chemo- and regioselectivity. D2O was used as a readily available and cheap source of deuterium. Mechanistic studies indicated that B(C6F5)3 could activate water to promote the protonation and reduction of enamines. This journal is
- Wu, Rongpei,Gao, Ke
-
supporting information
p. 4032 - 4036
(2021/05/19)
-
- Method for catalyzing hydrodesulfurization of thioamide derivative
-
The invention provides a method for catalyzing hydrodesulfurization of a thioamide derivative, which comprises the following steps: sequentially adding a pentacarbonyl manganese bromide catalyst, a reaction substrate thioamide derivative, Lewis acid, a solvent and alkali into a polytetrafluoroethylene lined reaction tube, putting the reaction tube into a high-pressure kettle, introducing hydrogen to carry out catalytic hydrogenation reaction, cooling to room temperature, discharging gas, washing the reaction tube with ethyl acetate, passing through a silica gel small short column, carrying out spin drying, and carrying out column chromatography purification to obtain a target product. The monovalent manganese which is low in toxicity and good in chemical selectivity and biocompatibility is used as the catalyst to catalyze hydrodesulfurization of the thioamide derivative, the substrate range is wide, the yield of amine is high, and the method has high drug synthesis application value.
- -
-
Paragraph 0044-0048
(2021/07/09)
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- Synthesis of Arylethylamines via C(sp3)-C(sp3) Palladium-Catalyzed Cross-Coupling
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Substituted arylethylamines represent a key structural motif in natural, pharmaceutical, and agrochemical compounds. Access to such scaffolds has been the subject of long-standing synthetic interest. Herein, we report the synthesis of such scaffolds via a palladium-catalyzed C(sp3)-C(sp3) coupling between (chloromethyl)aryls and air-/moisture-stable N,N-dialkylaminomethyltrifluoroborate salts. Rapid hit identification was achieved using microscale high-throughput experimentation and was followed by millimolar-scale reaction parameter optimization. A range of structurally and electronically varied arylethylamine products were obtained in moderate to excellent yields (27-96%, >60 examples). The reaction mechanism is proposed to proceed via formation of a trialkylbenzylammonium species prior to oxidative addition.
- Lippa, Rhys A.,Battersby, David J.,Murphy, John A.,Barrett, Tim N.
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p. 3583 - 3604
(2021/02/27)
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- Ambient Moisture Accelerates Hydroamination Reactions of Vinylarenes with Alkali-Metal Amides under Air
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A straightforward alkali-metal-mediated hydroamination of styrenes using biorenewable 2-methyltetrahydrofuran as a solvent is reported. Refuting the conventional wisdom of the incompatibility of organolithium reagents with air and moisture, shown here is that the presence of moisture is key in favoring formation of the target phenethylamines over competing olefin polymerization products. The method is also compatible with sodium amides, with the latter showing excellent promise as highly efficient catalysts under inert atmosphere conditions.
- Bole, Leonie J.,Davin, Laia,García-álvarez, Joaquín,Hernán-Gómez, Alberto,Hevia, Eva,Kennedy, Alan,Mulks, Florian F.
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supporting information
p. 19021 - 19026
(2020/09/01)
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- Alkali metal and stoichiometric effects in intermolecular hydroamination catalysed by lithium, sodium and potassium magnesiates
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Main group bimetallic complexes, while being increasingly used in stoichiometric deprotonation and metal-halogen exchange reactions, have not yet made a significant impact in catalytic applications. This paper explores the ability of alkali metal magnesiates to catalyse the intermolecular hydroamination of alkynes and alkenes using sytrene and diphenylacetylene as principle setting model substrates. By systematically studying the role of the alkali-metal and the formulation of the heterobimetallic precatalyst, this study establishes higher order potassium magnesiate [(PMDETA)2K2Mg(CH2SiMe3)4] (7) as a highly effective system capable of catalysing hydroamination of styrene and diphenylacetylene with several amines while operating at room temperature. This high reactivity contrasts with the complete lack of catalytic ability of neutral Mg(CH2SiMe3)2, even when harsher reaction conditions are employed (24 h, 80 °C). A pronounced alkali metal effect is also uncovered proving that the alkali metal (Li, Na, or K) is not a mere spectating counterion. Through stoichiometric reactions, and structural and spectroscopic (DOSY NMR) investigations we shed some light on the potential reaction pathway as well as the constitution of key intermediates. This work suggests that the enhanced catalytic activity of 7 can be rationalised in terms of the superior nucleophilic power of the formally dianionic magnesiate {Mg(NR2)4}2- generated in situ during the hydroamination process, along with the ability of potassium to engage in π-interactions with the unsaturated organic substrate, enhancing its susceptibility towards a nucleophilic attack by the amide anion.
- Davin, Laia,Hernán-Gómez, Alberto,McLaughlin, Calum,Kennedy, Alan R.,McLellan, Ross,Hevia, Eva
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p. 8122 - 8130
(2019/06/18)
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- SmI2(H2O)n Reduction of Electron Rich Enamines by Proton-Coupled Electron Transfer
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Samarium diiodide in the presence of water and THF (SmI2(H2O)n) has in recent years become a versatile and useful reagent, mainly for reducing carbonyl-type substrates. This work reports the reduction of several enamines by SmI2(H2O)n. Mechanistic experiments implicate a concerted proton-coupled electron transfer (PCET) pathway, based on various pieces of evidence against initial outer-sphere electron transfer, proton transfer, or substrate coordination. A thermochemical analysis indicates that the C-H bond formed in the rate-determining step has a bond dissociation free energy (BDFE) of ~32 kcal mol-1. The O-H BDFE of the samarium aquo ion is estimated to be 26 kcal mol-1, which is among the weakest known X-H bonds of stable reagents. Thus, SmI2(H2O)n should be able to form very weak C-H bonds. The reduction of these highly electron rich substrates by SmI2(H2O)n shows that this reagent is a very strong hydrogen atom donor as well as an outer-sphere reductant.
- Kolmar, Scott S.,Mayer, James M.
-
supporting information
p. 10687 - 10692
(2017/08/15)
-
- Tertiary amine synthesis: Via reductive coupling of amides with Grignard reagents
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A new iridium catalyzed reductive coupling reaction of Grignard reagents and tertiary amides affording functionalised tertiary amine products via an efficient and technically-simple one-pot, two-stage experimental protocol, is reported. The reaction-which can be carried out on gram-scale using as little as 1 mol% Vaska's complex [IrCl(CO)(PPh3)2] and TMDS as the terminal reductant for the initial reductive activation step-tolerates a broad range of tertiary amides from (hetero)aromatic to aliphatic (branched, unbranched and formyl) and a wide variety of alkyl (linear, branched), vinyl, alkynyl and (hetero)aryl Grignard reagents. The new methodology has been applied directly to bioactive molecule synthesis and the high chemoselectivity of the reductive coupling of amide has been exploited in late stage functionalization of drug molecules. This reductive functionalisation of tertiary amides provides a new and practical solution to tertiary amine synthesis.
- Xie, Lan-Gui,Dixon, Darren J.
-
p. 7492 - 7497
(2017/10/30)
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- Mild Hydrogenation of Amides to Amines over a Platinum-Vanadium Bimetallic Catalyst
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Hydrogenation of amides to amines is an important reaction, but the need for high temperatures and H2 pressures is a problem. Catalysts that are effective under mild reaction conditions, that is, lower than 30 bar H2 and 70 °C, have not yet been reported. Here, the mild hydrogenation of amides was achieved for the first time by using a Pt-V bimetallic catalyst. Amide hydrogenation, at either 1 bar H2 at 70 °C or 5 bar H2 at room temperature was achieved using the bimetallic catalyst. The mild reaction conditions enable highly selective hydrogenation of various amides to the corresponding amines, while inhibiting arene hydrogenation. Catalyst characterization showed that the origin of the catalytic activity for the bimetallic catalyst is the oxophilic V-decorated Pt nanoparticles, which are 2 nm in diameter.
- Mitsudome, Takato,Miyagawa, Kazuya,Maeno, Zen,Mizugaki, Tomoo,Jitsukawa, Koichiro,Yamasaki, Jun,Kitagawa, Yasutaka,Kaneda, Kiyotomi
-
supporting information
p. 9381 - 9385
(2017/08/01)
-
- Chelating Bis(1,2,3-triazol-5-ylidene) Rhodium Complexes: Versatile Catalysts for Hydrosilylation Reactions
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NHC-rhodium complexes (NHC=N-heterocyclic carbenes) have been widely used as efficient catalysts for hydrosilylation reactions. However, the substrates were mostly limited to reactive carbonyl compounds (aldehydes and ketones) or carbon-carbon multiple bonds. Here, we describe the application of newly-developed chelating bis(tzNHC)-rhodium complexes (tz=1,2,3-triazol-5-ylidene) for several reductive transformations. With these catalysts, the formal reductive methylation of amines using carbon dioxide, the hydrosilylation of amides and carboxylic acids, and the reductive alkylation of amines using carboxylic acids have been achieved under mild reaction conditions.
- Nguyen, Thanh V. Q.,Yoo, Woo-Jin,Kobayashi, Shu
-
supporting information
p. 452 - 458
(2016/02/12)
-
- Colloid and nanosized catalysts in organic synthesis: XIV. Reductive amination and amidation of carbonitriles catalyzed by nickel nanoparticles
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Hydrogenation of carbonitriles catalyzed by nickel nanoparticles in the presence of primary amines led to the predominant formation of unsymmetrical secondary amines. In the presence of secondary amines hydrogenation of nitrites provided enamines as main products. Hydrogenation of nitriles in the presence of formamide or acetamide afforded formyl or acetyl derivatives of primary amines.
- Popov, Yu. V.,Mokhov,Shcherbakova
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p. 798 - 805
(2016/06/13)
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- Copper-catalyzed oxygen atom transfer of N-oxides leading to a facile deoxygenation procedure applicable to both heterocyclic and amine N-oxides
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Deoxygenation of various types of N-oxides including both heterocyclic and alkyl(aryl)amine derivatives has successfully been developed by the copper-catalyzed oxygen atom transfer using diazo compounds as the oxygen acceptor. The reaction proceeds smoothly over a broad range of substrates with excellent functional group tolerance under mild conditions. This journal is
- Jeong, Jisu,Lee, Donggun,Chang, Sukbok
-
supporting information
p. 7035 - 7038
(2015/04/22)
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- Hydroamination of terminal alkynes with secondary amines catalyzed by copper: Regioselective access to amines
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A simple and convenient copper-catalyzed hydroamination of arylacetylenes with secondary amines has been performed giving a simple access to aliphatic amines after reduction of the hydroaminated products (E-enamines). Here we described a mild catalytic system utilizing CuCN precatalyst without any additive ligands in a solvent-free system.
- Bahri, Janet,Blieck, Rémi,Jamoussi, Bassem,Taillefer, Marc,Monnier, Florian
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p. 11210 - 11212
(2015/07/07)
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- Mild and selective Et2Zn-catalyzed reduction of tertiary amides under Hydrosilylation conditions
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Diethylzinc (Et2Zn) can be used as an efficient and chemoselective catalyst for the reduction of tertiary amides under mild reaction conditions employing cost-effective polymeric silane (PMHS) as the hydride source. Crucial for the catalytic activity was the addition of a substoichiometric amount of lithium chloride to the reaction mixture. A series of amides containing different additional functional groups were reduced to their corresponding amines, and the products were isolated in good-to-excellent yields.
- Kovalenko, Oleksandr O.,Volkov, Alexey,Adolfsson, Hans
-
supporting information
p. 446 - 449
(2015/03/05)
-
- Ruthenium-catalyzed N-alkylation of amines with alcohols under mild conditions using the borrowing hydrogen methodology
-
Using a simple amino amide ligand, ruthenium-catalyzed one-pot alkylation of primary and secondary amines with simple alcohols was carried out under a wide range of conditions. Using the alcohol as solvent, alkylation was achieved under mild conditions, even as low as room temperature. Reactions occurred with high conversion and selectivity in many cases. Reactions can also be carried out at high temperatures in organic solvent with high selectivity using stoichiometric amounts of the alcohol.
- Enyong, Arrey B.,Moasser, Bahram
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p. 7553 - 7563
(2014/09/17)
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- Interfacial hydrogenation and deamination of nitriles to selectively synthesize tertiary amines
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A novel one-pot method has been developed for the interfacial hydrogenation of nitriles to synthesize asymmetrical tertiary amines. The active Pt NWs allow for the preparation of a series of tertiary amines in excellent yields (up to 99.0%) and a mixed solvent is vital for the adjustment of the yield. And also, the reaction proceeded under mild conditions and is environmentally friendly.
- Lu, Shuanglong,Li, Chao,Wang, Jiaqing,Pan, Yue,Cao, Xueqing,Gu, Hongwei
-
supporting information
p. 11110 - 11113
(2014/10/15)
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- Reusable supported ruthenium catalysts for the alkylation of amines by using primary alcohols
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Efficient and recyclable ruthenium catalysts were synthesized from readily available polystyrene-or silica-supported phosphine ligands. Catalysts bound to the polymer support through an ether linkage showed good to excellent activity towards the N-alkylation of primary and secondary amines to afford the alkylated products in 62-99 % yield at 120-140°C. The supported phosphine ligand/ruthenium ratio was found to be crucial for higher catalytic activity and lower ruthenium leaching. The continuous flow N-alkylation of amines was demonstrated by using the supported catalyst in a column reactor. By adopting the hydrogen-borrowing strategy, the synthesis of the anti-Parkinson agent Piribedil was established in 98 % yield at 140°C. Support group steals the show: An efficient Ru-based heterogeneous catalyst from readily available supported phosphine ligands is developed. The nature of the linkage and the extent of ruthenium incorporation are crucial in determining the catalytic activity. The catalyst can be recycled and used under continuous flow in a packed-bed reactor. The alkylation of cyclic amines is achieved in excellent yield at moderate temperatures in the absence of any external base.
- Peishan, Siah,Dang, Tuan Thanh,Seayad, Abdul Majeed,Ramalingam, Balamurugan
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p. 808 - 814
(2014/03/21)
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- Mechanistic Studies on the Catalytic Oxidative Amination of Alkenes by Rhodium(I) Complexes with Hemilabile Phosphines
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Cationic rhodium(I) complexes with P,O-functionalised arylphosphine ligands are efficient catalysts for the regioselective anti-Markovnikov oxidative amination of styrene with piperidine. The mechanism of the catalytic reaction has been investigated by spectroscopic means under stoichiometric and catalytic conditions. In the presence of piperidine, the catalyst precursor [Rh{κ2-P,O-Ph2P(CH2)3OEt}2]+ (5) gave the piperidine complex [Rh{κ1-P-Ph2P(CH2)3OEt}2(HNC5H10)2]+ (8) that was transformed into the neutral amido-piperidine species [Rh{κ1-P-Ph2P(CH2)3OEt}2(NC5H10)(HNC5H10)] (9) under thermal conditions. NMR studies performed in the presence of styrene under catalytic conditions showed that 9 is a key species in the catalytic oxidative amination of styrene. Related cyclooctadiene-containing catalyst precursors [Rh(cod){κ1-P-Ph2P(CH2)3OEt}n]+ (n=1, 2) also gave 9 under the same conditions. The proposed catalytic cycle has been established by a series of DFT calculations including the transition states of the key steps that have been identified and characterised. These studies have shown that, after elimination of the enamine, regeneration of catalytic active species takes place by direct transfer of the proton of a piperidine ligand to the alkyl group resulting from the insertion of styrene into the Rh-H bond and formation of ethylbenzene. Against the expectations, the formation of a dihydride intermediate by NH oxidative addition is a highly energy-demanding process. Catalyst 5 has also been applied for the oxidative amination of substituted vinylarenes with several secondary cyclic and acyclic amines.
- Jimenez, M. Victoria,Bartolome, M. Isabel,Perez-Torrente, Jesus J.,Gomez, Daniel,Modrego, F. Javier,Oro, Luis A.
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p. 263 - 276
(2013/03/14)
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- An efficient palladium-catalyzed N-alkylation of amines using primary and secondary alcohols
-
PdCl2 in the presence of dppe or Xantphos(t-Bu) as the ligand is found to be an efficient catalyst for the N-alkylation of various primary and cyclic secondary amines using primary alcohols at 90-130 C under neat conditions. Interestingly, good to excellent yields were achieved when more challenging secondary alcohols were used as alkylating agents at 130-150 C. The reaction could be easily scaled up, as demonstrated for a 10 mmol scale achieving yields up to 90% with a TON of 900.
- Dang, Tuan Thanh,Ramalingam, Balamurugan,Shan, Siah Pei,Seayad, Abdul Majeed
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p. 2536 - 2540
(2013/11/19)
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- Heavier alkaline earth catalysts for the intermolecular hydroamination of vinylarenes, dienes, and alkynes
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The heavier group 2 complexes [M{N(SiMe3)2} 2]2(1, M = Ca; 2, M = Sr) and [M{CH(SiMe3) 2}2(THF)2] (3, M = Ca; 4, M = Sr) are shown to be effective precatalysts for the intermolecular hydroamination of vinyl arenes and dienes under mild conditions. Initial studies revealed that the amide precatalysts, 1 and 2, while compromised in terms of absolute activity by a tendency toward transaminative behavior, offer greater stability toward polymerization/oligomerization side reactions. In every case the strontium species, 2 and 4, were found to outperform their calcium congeners. Reactions of piperidine with para-substituted styrenes are indicative of rate-determining alkene insertion in the catalytic cycle while the ease of addition of secondary cyclic amines was found to be dependent on ring size and reasoned to be a consequence of varying amine nucleophilicity. Hydroamination of conjugated dienes yielded isomeric products via η3-allyl intermediates and their relative distributions were explained through stereoelectronic considerations. The ability to carry out the hydroamination of internal alkynes was found to be dramatically dependent upon the identity of the alkyne substituents while reactions employing terminal alkynes resulted in the precipitation of insoluble and unreactive group 2 acetylides. The rate law for styrene hydroamination with piperidine catalyzed by [Sr{N(SiMe3) 2}2]2 was deduced to be first order in [amine] and [alkene] and second order in [catalyst], while large kinetic isotope effects and group 2 element-dependent ΔS? values implicated the formation of an amine-assisted rate-determining alkene insertion transition state in which there is a considerable entropic advantage associated with use of the larger strontium center.
- Brinkmann, Christine,Barrett, Anthony G. M.,Hill, Michael S.,Procopiou, Panayiotis A.
-
supporting information; experimental part
p. 2193 - 2207
(2012/03/10)
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- Ru-catalyzed β-selective and enantioselective addition of amines to styrenes initiated by direct arene-exchange
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A catalytic β-selective addition of amines to styrenes proceeded in the presence of cationic Ru complexes combined with diphosphine ligands. In the reaction of α-methylstyrene, an enantioselective addition was achieved by using xylylBINAP.
- Otsuka, Maiko,Yokoyama, Hiroya,Endo, Kohei,Shibata, Takanori
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scheme or table
p. 3815 - 3818
(2012/06/04)
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- A mild one-pot conversion of alkenes into amines through tandem ozonolysis and reductive amination
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The selective reduction of hydroperoxyacetals to aldehydes by sodium triacetoxyborohydride provides the basis for a mild one-pot synthesis of amines from alkenes. Georg Thieme Verlag Stuttgart.
- Kyasa, Shivakumar,Fisher, Thomas J.,Dussault, Patrick H.
-
experimental part
p. 3475 - 3481
(2011/12/04)
-
- Time-dependent slowly-reversible inhibition of monoamine oxidase A by N-substituted 1,2,3,6-tetrahydropyridines
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A novel class of N-substituted tetrahydropyridine derivatives was found to have multiple kinetic mechanisms of monoamine oxidase A inhibition. Eleven structurally similar tetrahydropyridine derivatives were synthesized and evaluated as inhibitors of MAO-A and MAO-B. The most potent MAO-A inhibitor in the series, 2,4-dichlorophenoxypropyl analog 12, displayed time-dependent mixed noncompetitive inhibition. The inhibition was reversed by dialysis, indicating reversible enzyme inhibition. Evidence that the slow-binding inhibition of MAO-A with 12 involves a covalent bond was gained from stabilizing a covalent reversible intermediate product by reduction with sodium borohydride. The reduced enzyme complex was not reversible by dialysis. The results are consistent with slowly reversible, mechanism-based inhibition. Two tetrahydropyridine analogs that selectively inhibited MAO-A were characterized by kinetic mechanisms differing from the kinetic mechanism of 12. As reversible inhibitors of MAO-A, tetrahydropyridine analogs are at low risk of having an adverse effect of tyramine-induced hypertension.
- Wichitnithad, Wisut,O'Callaghan, James P.,Miller, Diane B.,Train, Brian C.,Callery, Patrick S.
-
experimental part
p. 7482 - 7492
(2012/02/02)
-
- Identification of isobaric product ions in electrospray ionization mass spectra of fentanyl using multistage mass spectrometry and deuterium labeling
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Isobaric product ions cannot be differentiated by exact mass determinations, although in some cases deuterium labeling can provide useful structural information for identifying isobaric ions. Proposed fragmentation pathways of fentanyl were investigated by electrospray ionization ion trap mass spectrometry coupled with deuterium labeling experiments and spectra of regiospecific deuterium labeled analogs. The major product ion of fentanyl under tandem mass spectrometry (MS/MS) conditions (m/z 188) was accounted for by a neutral loss of N-phenylpropanamide. 1-(2-Phenylethyl)- 1,2,3,6-tetrahydropyridine (1) was proposed as the structure of the product ion. However, further fragmentation (MS3) of the fentanyl m/z 188 ion gave product ions that were different from the product ion in the MS/MS fragmentation of synthesized 1, suggesting that the m/z 188 product ion from fentanyl includes an isobaric structure different from the structure of 1. MS/MS fragmentation of fentanyl in deuterium oxide moved one of the isobars to 1Da higher mass, and left the other isobar unchanged in mass. Multistage mass spectral data from deuterium-labeled proposed isobaric structures provided support for two fragmentation pathways. The results illustrate the utility of multistage mass spectrometry and deuterium labeling in structural assignment of isobaric product ions.
- Wichitnithad, Wisut,McManus, Terence J.,Callery, Patrick S.
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experimental part
p. 2547 - 2553
(2011/12/03)
-
- Three-component synthesis of α-branched amines under barbier-like conditions
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(Chemical Equation Presented) An array of α-branched amines has been prepared by using an expedient three-component Mannich-type reaction among organic halides, aldehyde derivatives, and amines. The experimental procedure, which is characterized by its simplicity, employs zinc dust for the in situ generation of organozinc reagents. We show that this Barbier-like protocol constitutes a useful entry to diarylmethylamines, 1,2-diarylethylamines, α- or β-amino esters, benzylamines, and β-arylethylamines.
- Le Gall, Erwan,Haurena, Caroline,Sengmany, Stephane,Martens, Thierry,Troupel, Michel
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supporting information; experimental part
p. 7971 - 7973
(2010/02/28)
-
- Broadening the scope of group 4 hydroamination catalysis using a tethered ureate ligand
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(Chemical Equation Presented) A broadly applicable group-4-based precatalyst for the hydroamination of primary and secondary amines was developed. Screening experiments involving a series of amide and urea proligands led to the discovery of a tethered bis(ureate) zirconium complex with unprecedented reactivity in the intermolecular hydroamination of alkynes and the intramolecular hydroamination of alkenes. This catalyst system is effective with primary and secondary amines, 1,2-disubstituted alkenes, and heteroatom-containing functional groups, including ethers, silanes, amines, and heteroaromatics. The gem-disubstituent effect is not required for cyclization. The catalyst is generally regioselective for the anti-Markovnikov product of intermolecular alkyne hydroamination, and chemoselective for hydroamination over C-alkylation when forming 6- and 7-membered rings from aminoalkenes.
- Leitch, David C.,Payne, Philippa R.,Dunbar, Christine R.,Schafer, Laurel L.
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supporting information; experimental part
p. 18246 - 18247
(2010/04/25)
-
- Base-catalyzed anti-Markovnikov hydroamination of vinylarenes - Scope, limitations and computational studies
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The hydroamination of vinylarenes with primary and secondary amines was studied with catalytic amounts as low as 2 mol-% of LiN(SiMe3) 2/TMEDA. Reactions proceeded readily at 120°C in the absence of solvent to give selective anti-Markovnikov addition. Slow addition was observed at 25°C with either electron-deficient p-chlorostyrene or secondary cyclic amines such as pyrrolidine, piperidine, or morpholine. Primary amines were prone to a second hydroamination reaction to form tertiary amine byproducts. The selectivity for the mono(hydroamination) products could be improved with a two-fold excess of the amine. KN(SiMe3)2 showed higher catalytic activity but lower selectivity in comparison to that of LiN(SiMe 3)2, resulting in undesired C-H-activation by-products. The mechanism of the lithium-catalyzed hydroamination and the influence of TMEDA was studied with density functional theory. Wiley-VCH Verlag GmbH & Co. KGaA, 2007.
- Horrillo-Martinez, Patricia,Hultzsch, Kai C.,Gil, Adria,Branchadell, Vicenc
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p. 3311 - 3325
(2008/02/10)
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- RUTHENIUM-CATALYZED HYDROAMINATION OF OLEFINS
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Applicants have unexpectedly discovered that catalysts made from a ruthenium catalyst precursor or preformed ruthenium catalysts as otherwise described in the present specification are capable of effecting the addition of a N-H bond across an olefin C=C (olefinic) bond of a substrate with a high degree of regioselectivity and enantioselectivity in high yield. These addition reactions proceed in an anti-Markovnikov or Markovnikov fashion depending upon the catalyst precursor used to generate the ruthenium catalyst which actually participates in the addition reaction. The present invention relates to methods of adding N-H bonds across an olefinic bond in a substrate, using a ruthenium catalyst precursor or catalyst I comprising a compound according to the general structure I: Formula (I) where Ru is a ruthenium atom; L1 represents one or more coordinated ancillary ligands, which may be all the same ligand or which may be a combination of different ligands, each of which may be neutral or formally charged, and each of which may be monodentate and coordinated to ruthenium through a single atom or which may be linked or chelated and bound through more than one atom; L2 represents one or more formally charged ligands which are the same or different and which are optionally susceptible to removal with a strong acid; and x is 0-6, preferably 1, y is 0-6, preferably 2 and n is 1-4, preferably 1.
- -
-
Page/Page column 22-23; 34
(2010/02/13)
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- Aminomethylation of organic halides promoted by zinc in protic medium
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Organic halides undergo smooth aminomethylation by secondary amines and aqueous formaldehyde promoted by metallic zinc under copper(I) catalysis. Good to excellent yields are obtained with primary, secondary, and tertiary iodides, allylic, propargylic, and benzylic bromides and with α-bromoesters. In most cases, DMSO is the best solvent, but dioxane is preferable for some more reactive halides. Additional experiments with radical quenchers and promoters and the use of 'radical clocks' indicate a stepwise reaction mechanism initiated by the attack of an alkyl radical to iminium ion.
- Estevam, Idália H. S.,Da Silva, Margarete F.,Bieber, Lothar W.
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p. 7601 - 7604
(2007/10/03)
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- Ruthenium-Catalyzed Anti-Markovnikov Hydroamination of Vinylarenes
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A ruthenium-catalyzed intermolecular, anti-Markovnikov hydroamination of vinylarenes with secondary aliphatic and benzylic amines is reported. The combination of Ru(cod)(2-methylallyl)2, 1,5-bis(diphenylphosphino)pentane, and triflic acid was the most effective catalyst of those tested. Control reactions conducted without ligand or acid did not form the amine. The reaction of morpholine, piperidine, 4-phenylpiperazine, 4-BOC-piperazine, 4-piperidone ethylene ketal, and tetrahydroisoquinoline with styrene in the presence of 5 mol % of this catalyst formed the corresponding β-phenethylamine products in 64?96% yield, with 99% regioselectivity, and without enamine side products. Acyclic amines such as n-hexylmethylamine and N-benzylmethylamine reacted with styrene in 63 and 50% yields, respectively. Alkyl-, methoxy-, and trifluoromethyl-substituted styrenes reacted with morpholine in the presence of this catalyst or a related one containing 1,1′-bis(diisopropylphosphino)ferrocene as ligand to give the products in 51?91%. Further, the hydroamination of α-methyl styrene was observed for the first time with a homogeneous transition metal catalyst. Preliminary mechanistic studies showed that the reaction occurred by direct, irreversible, anti-Markovnikov hydroamination and that the mechanism of the ruthenium-catalyzed hydroamination is likely to be distinct from that of the recently reported rhodium-catalyzed reaction. Copyright
- Utsunomiya, Masaru,Hartwig, John F.
-
p. 2702 - 2703
(2007/10/03)
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- Rhodium-catalyzed anti-Markovnikov hydroamination of vinylarenes
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The transition metal-catalyzed anti-Markovnikov hydroamination of unactivated vinylarenes with a rhodium complex of DPEphos is reported. The reaction of electron-neutral or electron-rich vinylarenes with a variety of secondary amines in the presence of catalyst forms the products from anti-Markovnikov hydroamination in high yields. Reactions of morpholine, N-phenylpiperazine, N-Boc-piperazine, piperidine, 2,5-dimethylmorpholine, and perhydroisoquinoline reacted with styrene to form the amine product in 51-71% yield. Reactions of a variety of vinylarenes with morpholine generated amine as the major product. Reactions of morpholine with electron-poor vinylarenes gave lower amine:enamine ratios than reactions of electron-rich vinylarenes at the same concentration of vinylarene, but conditions were developed with lower concentrations of electron-poor vinylarene to maintain formation of the amine as the major product. Reactions of dimethylamine with vinylarenes were fast and formed amine as the major product. Mechanistic studies on the hydroamination process showed that the amine:enamine ratio was lower for reactions conducted with higher concentrations of vinylarene and that one vinylarene influences the selectivity for reaction of another. A mechanism proceeding through a metallacyclic intermediate that opens in the presence of a second vinylarene accounts for these and other mechanistic observations. Copyright
- Utsunomiya, Masaru,Kuwano, Ryoichi,Kawatsura, Motoi,Hartwig, John F.
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p. 5608 - 5609
(2007/10/03)
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- Heterocyclic compounds and medical use thereof
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The present invention provides an AP-1 activation inhibitor, a NF-kappaB activation inhibitor, an inflammatory cytokine production inhibitor, a production inhibitor for matrix metalloprotease or an inflammatory cell adhesion factor expression inhibitor, which contains a heterocyclic compound or a pharmaceutically acceptable salt thereof as an active ingredient.
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- Reactions of alkyl, benzyl and stannyl halides with Lewis acid complexed α-lithiated tertiary amines
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α-amino stannanes can be obtained readily from tertiary amines through BF3 promoted deprotonation; in situ CsF treatment of BF3 complexed stannanes followed by lithium-transmetalation can be used to procure those α-alkylation product
- Kessar,Singh,Singh,Singh
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p. 517 - 518
(2007/10/03)
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- The first rhodium-catalyzed anti-markovnikov hydroamination: Studies on hydroamination and oxidative amination of aromatic olefins
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The first transition-metal-catalyzed regiospecific anti-Markovnikov hydroamination of aromatic olefins is reported. Styrene and substituted styrenes react with secondary aliphatic amines, especially morpholine and Narylpiperazines, in the presence of cationic rhodium complexes to give 2- aminoethenylbenzene and 2-aminoethylbenzene derivatives. Cationic [Rh(cod)2]+BF4- and various phosphines (l:2-mixture) were employed as in situ catalysts. According to labeling experiments, there is no evidence that the hydroamination is a consecutive hydrogenation of a previously formed enamine. Hydroamination with simple secondary amines, for example piperidine, can also be achieved by the use of a higher olefin concentration and higher reaction temperatures than those given in previously published reaction procedures. Kinetic investigations of the major reaction pathway reveal that the reaction rate of the oxidative amination and the hydroamination is dependent on the styrene and on the catalyst concentration, and independent of the amine concentration. Experiments that employed deuterium-labeled amines (N-D) provided evidence that the mechanism involves an amine- activating pathway. The substituents on the styrene, the phosphine ligand, and the solvent influence the yield of the aminations and the enamine:alkylamine ratio.
- Beller,Trauthwein,Eichberger,Breindl,Herwig,Mueller,Thiel
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p. 1306 - 1319
(2007/10/03)
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- Indirect monoalkylation of primary and secondary amines by reductive decyanation of α-aminonitriles with sodium cyanoborohydride-mercury bis(trifluoroacetate)
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Secondary and tertiary amines are prepared from α-aminonitriles by selective reductive cleavage of the cyanide moiety. The α-aminonitriles in this case, function as 'masked' imine or iminium ions and are 'unmasked' by mercury(II) in the presence of sodium cyanoborohydride to obtain the reduced product. Secondary amines may be prepared indirectly from primary amines in good yield without danger of over alkylation.
- Sassaman, Mark B.
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p. 10835 - 10840
(2007/10/03)
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- Radical cyclisations of imines and hydrazones
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Radical cyclisation of sp3 carbon-centred radicals onto imines and hydrazones provides a new method for the synthesis of 5- and 6-membered ring nitrogen heterocycles. Cyclisation onto the electrophilic carbon of the C=N group and 5-exo stereoelectronic selectivity are the dominating mechanistic parameters. The C-centred radical intermediates were generated from benzeneselenyl precursors using Bu3SnH.
- Bowman, W. Russell,Stephenson, Peter T.,Terrett, Nicholas K.,Young, Adrian R.
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p. 7959 - 7980
(2007/10/02)
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- Cyclisation of Carbinyl Radicals onto Imines and Hydrazones
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The regioselectivity of intramolecular addition of sp3 carbon-centered radicals onto C=N double bonds of imines and hydrazones is influenced by the position and polarisation of the C=N bond.
- Bowman, W. Russel,Stephenson, Peter T.,Terrett, Nicholas K.,Young, Adrian R.
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p. 6369 - 6372
(2007/10/02)
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- ALKYLATION OF AMINES USING TRIVALENT BISMUTH DERIVATIVES
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Mixed alkylaryl Bi(III) derivatives have been prepared by both anionic and free radical methods.The thermal stability of these compounds permits them to be used in the presence of cupric acetate for alkylation of amines.Trialkylbismuth compounds can also be used in the same way.
- Barton, Derek H. R.,Ozbalik, Nubar,Ramesh, Manian
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p. 857 - 860
(2007/10/02)
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- A New Method of α-Functionalization for Tertiary Amines by Nucleophilic Substitution of α-Siloxy Amines
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α-Siloxy amines, which were easily prepared by "silicon Polonovski reaction" of tertiary amine N-oxides with trialkylsilyl trifluoromethanesulfonate, were treated with various nucleophiles to give the corresponding α-functionalized tertiary amines in moderate to good yields.This new method has to the advantage that it enables the α-substitution of amines not only by alkyl groups but also by alkenyl and aryl groups with sp2 carbon as a reaction center, since the introduction of such groups is difficult in electrophilic substitution of dipole-stabilized α-lithio amines.Besides the organometallics such as Grignard and organoaluminum reagents, trimethylsilyl cyanide and silyl enol ether could also be employed as nucleophiles in the presence of an appropriate Lewis acid.
- Tokitoh, Norihiro,Okazaki, Renji
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p. 735 - 740
(2007/10/02)
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- HOMOLOGATION DES DERIVES HALOGENES
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The halide R-X is converted, in two steps, to its homologous R-CH2-X.
- Yankep, Emmanuel,Charles, Georges
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p. 427 - 430
(2007/10/02)
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- Ruthenium Complex Catalyzed N-Heterocyclization. Syntheses of N-Substituted Piperidines, Morpholines, and Piperazines from Amines and 1,5-Diols
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1,5-Pentanediol reacts with aliphatic and aromatic primary amines in the presence of a ruthenium catalyst modified with phosphonic ligands to give N-substituted piperidines in fair to goods yields.The reactions were carried out at 150-180 deg C for 5 h in dioxane.The nature of the phosphorus ligands has a remarkable effect on the catalytic activity, For the reaction of aromatic amines, triphenylphosphine is effective, while for aliphatic amine more basic tributyl- or triethylphosphine is preferable.Amines also react with diethylene glycol and N-substituted diethanolamines in the presence of the ruthenium catalyst to give N-substituted morpholines and piperazines in good yields, respectively.
- Tsuji, Yasushi,Huh, Keun-Tae,Ohsugi, Yukihiro,Watanabe, Yoshihisa
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p. 1365 - 1370
(2007/10/02)
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- A convenient method for the selective reduction of amides to amines
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A variety of amides have been selectively reduced to the corresponding amines via conversion to their thioamides and treatment with triethyloxonium tetrafluoroborate followed by sodium borohydride. This procedure is compatible with isolated and conjugated double bonds, esters, intro groups, and sulfonamides.
- Raucher, Stanley,Klein, Peter
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p. 4061 - 4064
(2007/10/02)
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