- Development of an Operationally Simple, Scalable, and HCN-Free Transfer Hydrocyanation Protocol Using an Air-Stable Nickel Precatalyst
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Hydrocyanation reactions enable access to synthetically valuable nitriles from readily available alkene precursors. However, hydrocyanation reactions using hydrogen cyanide (HCN) or similarly toxic reagents on laboratory scale can be particularly challenging due to their hazardous nature. In addition, such processes typically require air- and temperature-sensitive Ni(0) precatalysts, further reducing the operational simplicity of this transformation. Herein, we report a HCN-free transfer hydrocyanation of alkenes and alkynes that employs commercially available aliphatic nitriles as sacrificial HCN donors in combination with a catalytic amount of air-stable and inexpensive NiCl2as a precatalyst and a cocatalytic Lewis acid. The scalability and robustness of the catalytic process were demonstrated by the hydrocyanation of α-methylstyrene on a 100 mmol scale (11.4 g of product obtained) using 1 mol % of the Ni catalyst. In addition, the feasibility of the dehydrocyanation protocol using the air-stable Ni(II) precatalyst and norbornadiene as a sacrificial acceptor was showcased by the selective conversion of an aliphatic nitrile into the corresponding alkene.
- Bhawal, Benjamin N.,Jelmini, Nicola,Morandi, Bill,Reisenbauer, Julia C.
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supporting information
(2022/03/01)
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- Nickel-Catalyzed Deaminative Cyanation: Nitriles and One-Carbon Homologation from Alkyl Amines
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A nickel-catalyzed deaminative cyanation of Katritzky pyridinium salts has been developed. When it is coupled with formation of the pyridinium salt from primary amines, this method enables alkyl amines to be converted to alkyl nitriles. A less toxic cyanide reagent, Zn(CN)2, is utilized, and diverse functional groups and heterocycles are tolerated. The method also enables a one-carbon homologation of alkyl amines via reduction of the nitrile products, in addition to many other potential transformations of the versatile nitrile group.
- Xu, Jianyu,Twitty, J. Cameron,Watson, Mary P.
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supporting information
p. 6242 - 6245
(2021/08/23)
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- Nickel-Catalyzed Markovnikov Transfer Hydrocyanation in the Absence of Lewis Acid
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Hydrocyanation in the absence of toxic HCN gas is highly desirable. Addressing that challenge, transition-metal-catalyzed transfer hydrocyanation using safe HCN precursors has been developed, but these reagents generally require a Lewis acid for activation, and the control of regioselectivity often remains problematic. In this Letter, a Ni-catalyzed highly Markovnikov-selective transfer hydrocyanation that operates in the absence of any Lewis acid is reported. The readily prepared pro-aromatic 1-isopropylcyclohexa-2,5-diene-1-carbonitrile is used as the HCN source, and the reaction shows a broad substrate scope and high functional group tolerance. Terminal styrene derivatives, dienes, and internal alkynes are converted with good to excellent selectivities. Mechanistic studies provide insights into the origin of the regioselectivity.
- Frye, Nils L.,Bhunia, Anup,Studer, Armido
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supporting information
p. 4456 - 4460
(2020/06/03)
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- Preparation method of alkyl nitrile compound
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The invention discloses a preparation method of an alkyl nitrile compound. Specifically, the preparation method comprises the following step: in an organic solvent, in the presence of a protective gasand under the action of a catalyst, carrying out a reduction reaction as shown in the specification on olefin as shown in a formula I, a cyanation reagent and water, wherein the alkyl nitrile compound 1 is a compound II and/or a compound III. The preparation method provided by the invention is mild in condition, can realize hydrocyanation of olefin more safely and efficiently, and has good substrate universality and functional group compatibility.
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Paragraph 0130-0132; 0250-0252
(2020/08/18)
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- Overcoming Selectivity Issues in Reversible Catalysis: A Transfer Hydrocyanation Exhibiting High Kinetic Control
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Reversible catalytic reactions operate under thermodynamic control, and thus, establishing a selective catalytic system poses a considerable challenge. Herein, we report a reversible transfer hydrocyanation protocol that exhibits high selectivity for the thermodynamically less favorable branched isomer. Selectivity is achieved by exploiting the lower barrier for C-CN oxidative addition and reductive elimination at benzylic positions in the absence of a cocatalytic Lewis acid. Through the design of a novel type of HCN donor, a practical, branched-selective, HCN-free transfer hydrocyanation was realized. The synthetically useful resolution of a mixture of branched and linear nitrile isomers was also demonstrated to underline the value of reversible and selective transfer reactions. In a broader context, this work demonstrates that high kinetic selectivity can be achieved in reversible transfer reactions, thus opening new horizons for their synthetic applications.
- Bhawal, Benjamin N.,Ehinger, Christian,Morandi, Bill,Reisenbauer, Julia C.
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supporting information
p. 10914 - 10920
(2020/07/13)
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- Highly practical synthesis of nitriles and heterocycles from alcohols under mild conditions by aerobic double dehydrogenative catalysis
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A mild, aerobic, catalytic process for obtaining nitriles directly from alcohols and aqueous ammonia is described. The reaction proceeds via a dehydrogenation cascade mediated by catalytic CuI, bpy, and TEMPO in the presence of O2. The substrate scope is broad including various functionalized aromatic and aliphatic alcohols. This protocol enabled the one-pot synthesis of various biaryl heterocycles directly from commercially available alcohols.
- Yin, Weiyu,Wang, Chengming,Huang, Yong
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supporting information
p. 1850 - 1853
(2013/06/04)
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- HETEROCYCLIC COMPOUNDS FOR THE INHIBITION OF PASK
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Disclosed herein are new heterocyclic compounds and compositions and their application as pharmaceuticals for the treatment of disease. Methods of inhibiting PAS Kinase (PASK) activity in a human or animal subject are also provided for the treatment of diseases such as diabetes mellitus.
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Page/Page column 55
(2012/11/08)
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- Monoalkylation of acetonitrile by primary alcohols catalyzed by iridium complexes
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The monoalkylation of acetonitrile by primary alcohols was achieved in a one-pot sequence in the presence of iridium catalysts. A diversity of nitriles has been obtained from aryl- and alkyl-methanols in excellent yield.
- Anxionnat, Bruno,Gomez Pardo, Domingo,Ricci, Gino,Cossy, Janine
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supporting information; experimental part
p. 4084 - 4087
(2011/09/21)
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- Heteroatom-directed alkylcyanation of alkynes
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Alkanenitriles having a heteroatom such as nitrogen, oxygen, and sulfur at the γ-position are found to add across alkynes stereo-and regioselectively by nickel/Lewis acid catalysis to give highly substituted acrylonitriles. The heteroatom functionalities likely coordinate to the nickel center to make oxidative addition of the C-CN bonds of the alkyl cyanides kinetically favorable, forming a five-membered nickelacycle intermediate and, thus, preventing β-hydride elimination to allow the alkylcyanation reaction.
- Nakao, Yoshiaki,Yada, Akira,Hiyama, Tamejiro
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supporting information; experimental part
p. 10024 - 10026
(2010/10/04)
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- 1,3-BENZOTHIAZINONE DERIVATIVES AND USE THEREOF
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This invention provides a compound represented by the formula (I) :wherein R1 is a hydrogen atom, a halogen atom, hydroxy, nitro, optionally halogenated alkyl, alkoxy optionally having substituents, acyl or amino optionally having substituents;R2 is pyridyl, furyl, thienyl, pyrrolyl, quinolyl, pyrazinyl, pyrimidinyl, pyridazinyl, indolyl, tetrahydroquinolyl or thiazolyl, each of which may have substituents;n is 1 or 2; or a salt. And this invention provides a safe pharmaceutical comprising the compound of the formula (I) , which has an excellent apoptosis inhibitory effect and MIF binding effect, for preventing and/or treating heart disease, nervous degenerative disease, cerebrovascular disease, central nervous infectious disease, traumatorathy, demyelinating disease, bone and articular disease, kidney disease, liver disease, osteomyelodysplasia, AIDS, cancer, and the like.
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- RECYCLIZATION OF 2-(2-ACYLETHYL)PYRIDINIUM SALTS
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Recyclization of 2-(2-acylethyl)pyridinium salts on treatment with nucleophiles may occur in different ways, to give heterocyclic compounds of various classes, namely indoles (the Kost-Sagitullin reaction products), 4-aminoindoles, and 3-hydroxy-1,2,3,4-tetrahydroquinolines, the formation of which constitute novel reactions in the recyclization of pyridinium salts.
- Terenin, V. I.,Rumyantsev, A. N.,Nosyrev, P. V.,Gromov, S. P.,Bundel', Yu. G.
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p. 1016 - 1022
(2007/10/02)
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- Structural Factors Affecting the Basicity of ω-Pyridylalkanols, ω-Pyridylalkanamides and ω-Pyridylalkylamines
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The present paper describes the preparation by conventional methods (when not available commercially) and the pKa-determination of the α-, β- and γ-isomers of pyridylethanamide, 3-pyridylpropanamide, 4-pyridylbutanamide, 5-pyridylpentanamide, pyridylmethanol, 2-pyridylethanol, 3-pyridylpropanol, 4-pyridylbutanol, 5-pyridylpentanol, pyridylmethylamine, 2-pyridylethylamine, 3-pyridylpropylamine, 4-pyridylbutylamine, and 5-pyridylpentylamine.While a field effect accounts for many variations in pKa as a function of chain length, marked inductive effects are operative in some methyl and ethyl homologs.The pKa-decreasing influence of an intramolecular H-bond is also apparent in some lower homologs belonging to the α-series.
- Mayer, Joachim M.,Testa, Bernard
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p. 1868 - 1884
(2007/10/02)
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