- Industrial R&D on catalytic C-C and C-N coupling reactions: A personal account on goals, approaches and results
-
R&D issues for the application of Pd- and Ni-catalyzed C-C and C-N coupling reactions in the fine chemicals industry are discussed. In a first part, some background is given on industrial R&D and the role of C-C and C-N coupling for preparative applicatio
- Blaser, Hans-Ulrich,Indolese, Adriano,Naud, Frederic,Nettekoven, Ulrike,Schnyder, Anita
-
-
Read Online
- A novel and efficient arylation of malononitrile catalyzed by nickel(0) complexes
-
We report the first use of a nickel catalyst for the direct arylation of a β-difunctionalized compound, the malononitrile, from halogenated aromatic substrates. The catalytic system is quite simple: Ni(PPh3)3, generated in situ from
- Cristau,Vogel,Taillefer,Gadras
-
-
Read Online
- Single enantiomer, chiral donor-acceptor metal complexes from bisoxazoline pseudoracemates
-
Single enantiomer, chiral donor-acceptor metal complexes were synthesized via the self-discriminating zinc(II) complexation of a pseudoracemic mixture of donor/acceptor-substituted bisoxazoline derivatives.
- Atkins, Jeffery M.,Moteki, Shin A.,DiMagno, Stephen G.,Takacs, James M.
-
-
Read Online
- Design of an Electron-Withdrawing Benzonitrile Ligand for Ni-Catalyzed Cross-Coupling Involving Tertiary Nucleophiles
-
The design of new ligands for cross-coupling is essential for developing new catalytic reactions that access valuable products such as pharmaceuticals. In this report, we exploit the reactivity of nitrile-containing additives in Ni catalysis to design a benzonitrile-containing ligand for cross-coupling involving tertiary nucleophiles. Kinetic and Hammett studies are used to elucidate the role of the optimized ligand, which demonstrate that the benzonitrile moiety acts as an electron-acceptor to promote reductive elimination over β-hydride elimination and stabilize low-valent Ni. With these conditions, a protocol for decyanation-metalation and Ni-catalyzed arylation is conducted, enabling access to quaternary α-arylnitriles from disubstituted malononitriles.
- Edjoc, Racquel K.,Mills, L. Reginald,Rousseaux, Sophie A. L.
-
supporting information
p. 10422 - 10428
(2021/07/26)
-
- Structure-Activity Relationships of Pyrazolo[1,5- a]pyrimidin-7(4 H)-ones as Antitubercular Agents
-
Pyrazolo[1,5-a]pyrimidin-7(4H)-one was identified through high-throughput whole-cell screening as a potential antituberculosis lead. The core of this scaffold has been identified several times previously and has been associated with various modes of actio
- Oh, Sangmi,Libardo, M. Daben J.,Azeeza, Shaik,Pauly, Gary T.,Roma, Jose Santinni O.,Sajid, Andaleeb,Tateishi, Yoshitaka,Duncombe, Caroline,Goodwin, Michael,Ioerger, Thomas R.,Wyatt, Paul G.,Ray, Peter C.,Gray, David W.,Boshoff, Helena I. M.,Barry, Clifton E.
-
p. 479 - 492
(2021/01/26)
-
- Preparation of O-Protected Cyanohydrins by Aerobic Oxidation of α-Substituted Malononitriles in the Presence of Diarylphosphine Oxides
-
A mild, reagent-cyanide-free, and efficient synthesis of O-phosphinoyl-protected cyanohydrins from readily available α-substituted malononitriles was realized using diarylphosphine oxides in the presence of O2. Mechanistic studies indicated that in addition to the initial aerobic oxidation of the malononitrile derivative notable features of this process include the formation of a tetrahedral intermediate and a subsequent intramolecular rearrangement. The phosphinoyl-protecting group can be removed by alcoholysis or by reduction with DIBAL-H.
- Zhang, Dapeng,Lian, Mingming,Liu, Jia,Tang, Shukun,Liu, Guangzhi,Ma, Cunfei,Meng, Qingwei,Peng, Haisheng,Zhu, Daling
-
supporting information
p. 2597 - 2601
(2019/04/17)
-
- A one-pot electrophilic cyanation–functionalization strategy for the synthesis of disubstituted malononitriles
-
Malononitriles are valuable synthetic intermediates for many applications, including the synthesis of herbicides and other biologically active molecules, and the synthesis of chiral ligands for asymmetric catalysis. This article describes the development of a procedure for the conversion of primary nitriles to malononitriles using dimethylmalononitrile, a commercial, non-toxic, carbon-bound source of electrophilic cyanide. This procedure avoids the use of toxic cyanide or malononitrile as a starting material. This protocol is further applied to the dicyanation of benzyl Grignard reagents, generated from benzyl bromides, yielding fully functionalized malononitriles from a nitrile-free precursor.
- Mills, L. Reginald,Rousseaux, Sophie A.L.
-
p. 4298 - 4306
(2019/05/22)
-
- Titanium(III)-Catalyzed Reductive Decyanation of Geminal Dinitriles by a Non-Free-Radical Mechanism
-
A titanium-catalyzed mono-decyanation of geminal dinitriles is reported. The reaction proceeds under mild conditions, tolerates numerous functional groups, and can be applied to quaternary malononitriles. A corresponding desulfonylation is demonstrated as well. Mechanistic experiments support a catalyst-controlled cleavage without the formation of free radicals, which is in sharp contrast to traditional stoichiometric radical decyanations. The involvement of two TiIII species in the C?C cleavage is proposed, and the beneficial role of added ZnCl2 and 2,4,6-collidine hydrochloride is investigated.
- Weweler, Jens,Younas, Sara L.,Streuff, Jan
-
supporting information
p. 17700 - 17703
(2019/11/13)
-
- Ni-Catalyzed Reductive Cyanation of Aryl Halides and Phenol Derivatives via Transnitrilation
-
Herein, we report a Ni-catalyzed reductive coupling for the synthesis of benzonitriles from aryl (pseudo)halides and an electrophilic cyanating reagent, 2-methyl-2-phenyl malononitrile (MPMN). MPMN is a bench-stable, carbon-bound electrophilic CN reagent that does not release cyanide under the reaction conditions. A variety of medicinally relevant benzonitriles can be made in good yields. Addition of NaBr to the reaction mixture allows for the use of more challenging aryl electrophiles such as aryl chlorides, tosylates, and triflates. Mechanistic investigations suggest that NaBr plays a role in facilitating oxidative addition with these substrates.
- Mills, L. Reginald,Graham, Joshua M.,Patel, Purvish,Rousseaux, Sophie A. L.
-
supporting information
p. 19257 - 19262
(2019/12/02)
-
- Design and evaluation of pyrazolopyrimidines as KCNQ channel modulators
-
Effective treatments of neuropathic pain have been a focus of many discovery programs. KCNQ (kv7) are voltage gated potassium channel openers that have the potential for the treatment of CNS disorders including neuropathic pain. Clinical studies have sugg
- Osuma, Augustine T.,Xu, Xiangdong,Wang, Zhi,Van Camp, Jennifer A.,Freiberg, Gail M.
-
-
- Nucleophilic Reactivities of Bis-Acceptor-Substituted Benzyl Anions
-
The kinetics of the reactions of bis-acceptor-substituted benzyl anions (PhCXY–, X,Y = CN, CO2Et, COPh, SO2Ph) with benzhydrylium ions and quinone methides (reference electrophiles) have been determined in dimethyl sulfoxide solution at 20 °C. The reactions follow second-order kinetics, first order with respect to the electrophile and first order with respect to the carbanion. The addition of 18-crown-6 ether, which efficiently coordinates to the anions' counter ions K+, did not affect the kinetics, which indicates that the measured rate constants refer to the reactivities of the nonpaired carbanions. Comparison with the reactivities of the structurally analogous secondary carbanions HCXY– shows that replacement of H at the carbanionic center by Ph reduces the nucleophilic reactivities towards a reference benzhydrylium ion by factors in the range of only 1.2 (X,Y = SO2Ph) to 6 (X,Y = CO2Et). The plots of lg k2 versus the electrophilicity parameters E of the reference electrophiles are linear, thereby indicating that the correlation lg k2(20 °C) = sN(E + N), which characterizes nucleophiles by the two solvent-dependent parameters sN and N and electrophiles by the parameter E, is applicable. In this way, it becomes possible to integrate these carbanions into our comprehensive nucleophilicity scale, which provides a direct comparison of the nucleophilic reactivities of different families of compounds.
- Puente, ángel,Ofial, Armin R.,Mayr, Herbert
-
supporting information
p. 1196 - 1202
(2017/03/11)
-
- AlCl3 catalyzed coupling of: N-benzylic sulfonamides with 2-substituted cyanoacetates through carbon-nitrogen bond cleavage
-
A new cross-coupling reaction of N-benzylic sulfonamides with 2-substituted cyanoacetates for the synthesis of 2-substituted benzylbenzene was reported. In the presence of AlCl3, a broad range of N-benzylic sulfonamides reacted smoothly with 2-substituted cyanoacetates to afford structurally diverse benzylbenzenes in moderate to excellent yields. The conversion could be enlarged to gram-scale efficiently. The practicability of this approach was further manifested in the synthesis of a related bioactive agent with high anti-inflammatory activity.
- Hu, Chen,Hong, Gang,Qian, Xiaofei,Kim, Kwang Rim,Zhu, Xiaoyan,Wang, Limin
-
supporting information
p. 4984 - 4991
(2017/07/10)
-
- Sterically Demanding Oxidative Amidation of α-Substituted Malononitriles with Amines Using O2
-
An efficient amidation method between readily available 1,1-dicyanoalkanes and either chiral or nonchiral amines was realized simply with molecular oxygen and a carbonate base. This oxidative protocol can be applied to both sterically and electronically challenging substrates in a highly chemoselective, practical, and rapid manner. The use of cyclopropyl and thioether substrates support the radical formation of α-peroxy malononitrile species, which can cyclize to dioxiranes that can monooxygenate malononitrile α-carbanions to afford activated acyl cyanides capable of reacting with amine nucleophiles.
- Li, Jing,Lear, Martin J.,Hayashi, Yujiro
-
supporting information
p. 9060 - 9064
(2016/07/26)
-
- Thiazole formation through a modified Gewald reaction
-
The synthesis of thiazoles and thiophenes starting from nitriles, via a modified Gewald reaction has been studied for a number of different substrates. 1,4-Dithiane-2,5-diol was used as the aldehyde precursor to give either 2-substituted thiazoles or 2-substituted aminothiophenes depending on the substitution of the α-carbon to the cyano group.
- Mallia, Carl J.,Englert, Lukas,Walter, Gary C.,Baxendale, Ian R.
-
supporting information
p. 875 - 883
(2015/08/24)
-
- How iodide anions inhibit the phase-transfer catalyzed reactions of carbanions
-
The inhibitory effect of iodide anions on the phase-transfer catalyzed reactions of carbanions generated in liquid-liquid two-phase systems by aqueous NaOH is due to preferential location of these anions in the interfacial region of the two-phase system-organic phase/concd aqueous NaOH. In such situation, the basic activity of NaOH in this region is decreased and the equilibrium of deprotonation of the carbanion precursors is disfavoured.
- Makosza, Mieczys?aw,Chesnokov, Alexey
-
p. 5925 - 5932
(2008/12/20)
-
- Facile one-pot synthesis of 2-aryl-substituted nitriles and 2-aryl-3-keto nitriles via benzyne reaction
-
2-Aryl-substituted nitriles were prepared in good to excellent yields in a one-pot reaction by the reaction of benzyne, generated using neutral conditions from (phenyl)[o-(trimethylsilyl)-phenyl]iodonium triflate, and 2-lithionitriles. 3-Keto nitriles substituted at the 2-position were obtained in good yields when these reactions were trapped with acid chlorides. The mechanism of the benzyne reaction in terms of a N-lithiobenzocyclobutanimine intermediate is discussed. Copyright Taylor & Francis Group, LLC.
- Kamila, Sukanta,Koh, Benjamin,Biehl, Edward R.
-
p. 3493 - 3507
(2007/10/03)
-
- A convenient protocol for the synthesis of hindered aryl malononitriles
-
A technically feasible method has been developed for the synthesis of variety of aryl malononitriles in high yields (70-95%) using the palladium-catalyzed coupling reaction of malononitrile with aryl bromides and chlorides, respectively. The influence a s
- Schnyder, Anita,Indolese, Adriano F.,Maetzke, Thomas,Wenger, Jean,Blaser, Hans-Ulrich
-
p. 3167 - 3169
(2008/02/13)
-
- Method of forming a carbon-carbon or carbon-heteroatom linkage
-
The invention relates to a method of creating a carbon-carbon or carbon-heteroatom linkage by reacting an unsaturated compound bearing a leaving group and a nucleophilic compound. More specifically, the invention relates to the creation of a carbon-nitrogen linkage involving the arylation of nitrogenous organic derivatives. The inventive method consists in creating a carbon-carbon or carbon-heteroatom linkage by reacting an unsaturated compound bearing a leaving group and a nucleophilic compound providing a carbon atom or a heteroatom (HE) capable of being substituted for the leaving group, thereby creating a C—C or C-HE linkage. The invention is characterised in that the reaction is carried out in the presence of an effective quantity of a catalyst based on copper and at least one ligand comprising at least one imine function and at least one additional nitrogen atom as chelating atoms
- -
-
Page/Page column 39-40
(2010/02/14)
-
- Highly efficient and mild copper-catalyzed N- and C-arylations with aryl bromides and iodides
-
Mild, efficient, copper-catalyzed N-arylation procedures for nitrogen heterocycles, amides, carbamates, and C-arylation procedures for malonic acid derivatives have been developed that afford high yields of arylated products with excellent selectivity. The N-arylation of imidazole with aryl bromides or iodides was found to be greatly accelerated by inexpensive, air-stable catalyst systems, combining catalytic copper salts or oxides with a set of structurally simple chelating ligands. The reaction was shown to be compatible with a broad range of aryl halides, encompassing sterically hindered, electron-poor, and electron-rich ones, providing the arylated products under particularly mild conditions (50-82°C). The lower limit in ligand and catalyst loading and the scope of Ullmann-type condensations catalyzed by complexes bearing those ligands with respect to the nucleophile class have also been investigated. Chelating Schiff base Chxn-Py-Al (1c) generates a remarkably general copper catalyst for N-arylation of pyrrole, indole, 1,2,4-triazole, amides, and carbamates; and C-arylation of diethyl malonate, ethyl cyanoacetate, and malononitrile with aryl iodides under mild conditions (50-82°C). The new method reported here is the most successful to date with regard to Ullmann-type arylation of some of these nucleophiles.
- Cristau, Henri-Jean,Cellier, Pascal P.,Spindler, Jean-Francis,Taillefer, Marc
-
p. 5607 - 5622
(2007/10/03)
-
- PROCESS FOR THE PREPARATION OF PHENYLMALONIC ACID DINITRILES
-
Phenylmalonic acid dinitriles are prepared by reaction of, for example, phenyl Kalides with malonic acid dinitrile in the presence of palladium catalysts and bases.
- -
-
-
- A highly efficient catalytic system for cross-coupling of aryl chlorides and bromides with malononitrile anion by palladium carbene complexes
-
Six imidazolium chlorides (1-6) as precursors of 1,3-diaryl substituted N-heterocyclic carbene ligands were synthesized and evaluated in palladium-catalyzed cross-coupling reactions of aryl chlorides and bromides with malononitrile in the presence of NaH.
- Gao, Chengwei,Tao, Xiaochun,Qian, Yanlong,Huang, Jiling
-
p. 1444 - 1445
(2007/10/03)
-
- The conversion of phenylpropanedinitrile (phenylmalononitrile) into the carbanion, followed by IR spectra, ab initio and DFT force field calculations.
-
The spectral and structural changes, caused by the conversion of phenylpropanedinitrile (phenylmalononitrile) into the carbanion, have been followed by IR spectra, ab initio HF, MP2 and DFT BLYP force field calculations. In agreement between theory and ex
- Binev, Yuri I,Georgieva, Miglena K,Novkova, Snezhana I
-
p. 3041 - 3052
(2007/10/03)
-
- A convenient and efficient palladium-catalyzed system for cross-coupling of aryl bromides with active methylene compounds
-
A simply catalytic system containing palladium-phosphine complex, generated in situ from PdCl2/tert-phosphino ligand in pyridine, has been systematically studied in the cross-coupling of bromobenzene with malononitrile or ethyl cyanoacetate anion. The effect of molar ratio of phosphine ligand to PdCl2 on the activity of the coupling was also discussed. It is found that the catalytic system has highly catalytic activity to produce aryl malononitriles and cyanoacetates in considerable yields (67-90%) when the substituted aryl bromides were used as substrates.
- Gao, Chengwei,Tao, Xiaochun,Qian, Yanlong,Huang, Jiling
-
p. 1716 - 1718
(2007/10/03)
-
- Anomalous Reaction of Arylmalononitriles with Nitric Acid. Para-Directing Nature of Dicyanomethyl Group and a Through-Ring Nitro/aci-Nitro Tautomerism of 4-Nitrophenylmalononitrile
-
Phenylmalononitrile reacts with nitric acid in dichloromethane at room temperature to afford 1,2-bis(4-nitrophenyl)-1,1,2,2-tetracyanoethane as an initial product, which readily suffers oxidative cleavage to give 4-nitrobenzoyl cyanide.Contrary to common
- Suzuki, Hitomi,Koide, Hideki,Ogawa, Takuji
-
p. 501 - 504
(2007/10/02)
-
- Cross-Coupling of N-Heteroaryl Halides with Active Methylene Compounds in the Presence of Tetrakis(triphenylphosphine)palladium
-
The cross-coupling of 3-iodo- and 3-bromopyridine with the carbanions derived from ethyl cyanoacetate and malononitrile in the presence of tetrakis(triphenylphosphine)palladium in 1,2-dimethoxyethane gave ethyl α-cyanopyridine-3-acetate and 3-pyridinemalononitrile in moderate yields.This palladium-catalyzed cross-coupling proceeded smoothly with halopyrimidines, haloquinolines, haloisoquinones, and also bromobenzene.Keywords - tetrakis(triphenylphosphine)palladium; aryl halide; N-heteroaryl halide; ethyl cyanoacetate; malononitrile; ethyl α-cyanoareneacetate; arenemalononitrile.
- Sakamoto, Takao,Katoh, Eisaku,Kondo, Yoshinori,Yamanaka, Hiroshi
-
p. 1664 - 1668
(2007/10/02)
-
- Photoelectron Spectra and Molecular Properties, 110. Tricyanomethane Derivatives X-C(CN)3
-
The photoelectron spectra of tricyanomethane derivatives X-C(CN)3 with substituents X = H, CH3, Br and C6H5 have been recorded and are assigned based on MNDO calculations as well as on radical cation state comparison with the iso(valence)electronic P(CN)3
- Bock, Hans,Dammel, Ralph
-
p. 315 - 322
(2007/10/02)
-
- Termodynamics and Kinetics of Carbon-Carbon Bond Formation and Heterolysis Through Reactions of Carbocations with Carbanions in Solution
-
Rate data are presented for the heterolysis of carbon-carbon bonds and their formation through coordination of resonance-stabilized carbocations and carbanions in acetonitrile solution at 25 deg C.These rates were determined by NMR line broadening and by the T jump technique (in a solution containing 0.48 M supporting electrolyte).Preliminary results are given for a "master equation" to predict some heterolysis energies in solution as a complement to Benson's method for homolysis energies.The results provide for the first time an opportunity to compare the effects of structure variation on the kinetic and thermodynamic properties for such an ostensibly simple reaction in solution.All evidence so far accumulated indicates that these reactions are dominated by ion-solvation factors so that they have little bearing on the gas-phase heterolysis energies.Ionic strength effects and substituent variation suggest that charge development is about half developed at the transition state, but we argue that this cannot be translated simply into pictures of transition-state structure.The results provide a flagrant reversal of the frequently invoked "reactivity selectivity principle" since the most reactive cation is also most selective.On the basis of these results and many others which have appeared recently it may be appropriate to discard the reactivity selectivity principle as a useful principle for either prediction or interpretation.
- Arnett, Edward M.,Molter, Kent
-
p. 383 - 389
(2007/10/02)
-
- A NEW APPROACH TO ARYLMALONONITRILES
-
Arylmalononitriles were prepared from the corresponding benzoyl chlorides by three reaction steps.Treatment of the starting substances with cyanotrimethylsilane in the presence of pyridine gave dicyanotrimethylsiloxymethylbenzenes, which were transformed
- Yamaguchi, Shunro,Araki, Hisashi,Hanafusa, Terukiyo
-
p. 685 - 688
(2007/10/02)
-
- A NEW ROUTE TO PHENYLENEDIMALONITRILE AND THE ANALOGUES USING PALLADIUM-CATALYZED CARBON-CARBON BOND FORMATION
-
Phenylenedimalonitrile and the analogues, which are key intermediates in the synthesis of TCNQ and the analogues, are prepared directly by the Pd-catalyzed reaction of diiodoarenes with malononitrile anion.
- Uno, M.,Seto, K.,Masuda, M.,Ueda, W.,Takahashi, S.
-
p. 1553 - 1556
(2007/10/02)
-
- A New Method of Synthesis of Arylmalononitriles catalysed by a Palladium Complex
-
Arylmalononitriles are prepared in good yields using a palladium-catalysed coupling reaction between aryl halides and malononitrile.
- Uno, Mitsunari,Seto, Koji,Takahashi, Shigetoshi
-
p. 932 - 933
(2007/10/02)
-
- Translocative Rearrangements. Generality of the Formamidine-Induced Rearrangement of 4-Substituted 5-Amino-4-cyano-4H-imidazoles
-
The generality of two different courses of cyclisation reactions for 4-substituted 5-amino-4-cyano-4H-imidazoles (5) is demonstrated.One results from treatment of 5 with formamidine in a "translocative rearrangement" that leads to 8-substituted 4-aminoimi
- Balicki, Roman,Hosmane, Ramachandra S.,Leonard, Nelson J.
-
-
- A FACILE SYNTHETIC ROUTE TO SOME ARYLMALONONITRILES
-
Copper(I) iodide-assisted reaction of aryl iodides with malononitrile anion provides a convenient route to some arylmalononitriles.
- Suzuki, Hitomi,Kobayashi, Tsutomu,Osuka, Atsuhiro
-
p. 589 - 590
(2007/10/02)
-
- THERMOLYSIS AND PHOTOLYSIS OF 4-DIAZO-1,2,3-TRIAZOLES IN BENZENOID SOLVENTS, SYSTEMS WHICH REVEAL DECOMPOSITION OF DIAZO COMPOUNDS TO CARBENES TO DIAZO COMPOUNDS TO CARBENES.
-
4-Diazo-1,2,3-triazoles thermolyze and photolyze to 4H-1,2,3-triazolylidenes which (1) convert benzenes to 4-phenyl-1,2,3-triazoles or/and (2) isomerize to α-diazonitriles which react carbenically with benzenes by addition, ring-expansion or substitution processes.
- Hui, H. K.-W.,Shechter, H.
-
p. 5115 - 5118
(2007/10/02)
-