5221-40-9Relevant academic research and scientific papers
In Situ Formation of Cationic π-Allylpalladium Precatalysts in Alcoholic Solvents: Application to C-N Bond Formation
Steinsoultz, Philippe,Bailly, Aurélien,Wagner, Patrick,Oliva, Estefania,Schmitt, Martine,Grimaud, Laurence,Bihel, Frédéric
, p. 560 - 567 (2022/01/03)
We report an efficient Buchwald-Hartwig cross-coupling reaction in alcoholic solvent, in which a low catalyst loading showed excellent performance for coupling aryl halides (I, Br, and Cl) with a broad set of amines, amides, ureas, and carbamates under mild conditions. Mechanistically speaking, in a protic and polar medium, extremely bulky biarylphosphine ligands interact with the dimeric precatalyst [Pd(π-(R)-allyl)Cl]2 to form the corresponding cationic complexes [Pd(π-(R)-allyl)(L)]Cl in situ and spontaneously. The resulting precatalyst further evolves under basic conditions into the corresponding L-Pd(0) catalyst, which is commonly employed for cross-coupling reactions. This mechanistic study highlights the prominent role of alcoholic solvents for the formation of the active catalyst.
N-Ammonium Ylide Mediators for Electrochemical C-H Oxidation
Saito, Masato,Kawamata, Yu,Meanwell, Michael,Navratil, Rafael,Chiodi, Debora,Carlson, Ethan,Hu, Pengfei,Chen, Longrui,Udyavara, Sagar,Kingston, Cian,Tanwar, Mayank,Tyagi, Sameer,McKillican, Bruce P.,Gichinga, Moses G.,Schmidt, Michael A.,Eastgate, Martin D.,Lamberto, Massimiliano,He, Chi,Tang, Tianhua,Malapit, Christian A.,Sigman, Matthew S.,Minteer, Shelley D.,Neurock, Matthew,Baran, Phil S.
supporting information, p. 7859 - 7867 (2021/05/26)
The site-specific oxidation of strong C(sp3)-H bonds is of uncontested utility in organic synthesis. From simplifying access to metabolites and late-stage diversification of lead compounds to truncating retrosynthetic plans, there is a growing need for new reagents and methods for achieving such a transformation in both academic and industrial circles. One main drawback of current chemical reagents is the lack of diversity with regard to structure and reactivity that prevents a combinatorial approach for rapid screening to be employed. In that regard, directed evolution still holds the greatest promise for achieving complex C-H oxidations in a variety of complex settings. Herein we present a rationally designed platform that provides a step toward this challenge using N-ammonium ylides as electrochemically driven oxidants for site-specific, chemoselective C(sp3)-H oxidation. By taking a first-principles approach guided by computation, these new mediators were identified and rapidly expanded into a library using ubiquitous building blocks and trivial synthesis techniques. The ylide-based approach to C-H oxidation exhibits tunable selectivity that is often exclusive to this class of oxidants and can be applied to real-world problems in the agricultural and pharmaceutical sectors.
N-pyridinylbenzamides: an isosteric approach towards new antimycobacterial compounds
Nawrot, Daria,Suchánková, Eli?ka,Jan?ourek, Ond?ej,Kone?ná, Klára,Bárta, Pavel,Dole?al, Martin,Zitko, Jan
, p. 686 - 700 (2020/11/30)
A series of N-pyridinylbenzamides was designed and prepared to investigate the influence of isosterism and positional isomerism on antimycobacterial activity. Comparison to previously published isosteric N-pyrazinylbenzamides was made as an attempt to draw structure–activity relationships in such type of compounds. In total, we prepared 44 different compounds, out of which fourteen had minimum inhibitory concentration (MIC) values against Mycobacterium tuberculosis H37Ra below 31.25?μg/ml, most promising being N-(5-chloropyridin-2-yl)-3-(trifluoromethyl)benzamide (23) and N-(6-chloropyridin-2-yl)-3-(trifluoromethyl)benzamide (24) with MIC?=?7.81?μg/ml (26?μm). Five compounds showed broad-spectrum antimycobacterial activity against M. tuberculosis H37Ra, M. smegmatis and M. aurum. N-(pyridin-2-yl)benzamides were generally more active than N-(pyridin-3-yl)benzamides, indicating that N-1 in the parental structure of N-pyrazinylbenzamides might be more important for antimycobacterial activity than N-4. Marginal antibacterial and antifungal activity was observed for title compounds. The hepatotoxicity of title compounds was assessed in vitro on hepatocellular carcinoma cell line HepG2, and they may be considered non-toxic (22 compounds with IC50 over 200?μm).
Direct Amidation of Esters by Ball Milling**
Barreteau, Fabien,Battilocchio, Claudio,Browne, Duncan L.,Godineau, Edouard,Leitch, Jamie A.,Nicholson, William I.,Payne, Riley,Priestley, Ian
supporting information, p. 21868 - 21874 (2021/09/02)
The direct mechanochemical amidation of esters by ball milling is described. The operationally simple procedure requires an ester, an amine, and substoichiometric KOtBu and was used to prepare a large and diverse library of 78 amide structures with modest to excellent efficiency. Heteroaromatic and heterocyclic components are specifically shown to be amenable to this mechanochemical protocol. This direct synthesis platform has been applied to the synthesis of active pharmaceutical ingredients (APIs) and agrochemicals as well as the gram-scale synthesis of an active pharmaceutical, all in the absence of a reaction solvent.
Synthesis of 2-Amino-1,3-dienes from Propargyl Carbonates via Palladium-Catalyzed Carbon-Nitrogen Bond Formation
O'Broin, Calvin Q.,Guiry, Patrick J.
supporting information, p. 879 - 883 (2020/02/04)
A catalytic method to synthesize 1,3,-dienes from propargylic precursors is reported. This palladium-catalyzed carbon-nitrogen bond-forming reaction furnishes 2-amino-1,3-dienes in excellent yields (up to 98%) and shows a broad tolerance to functional group diversity. The reaction has been demonstrated for over 30 amine substrates, including anilines and indoles, and proceeds under mild neutral conditions. The resulting 1,3-dienes are of great synthetic interest because of their further reaction potential.
Compound containing bipyrazole ring, intermediate thereof and application thereof
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Paragraph 0284-0286, (2020/05/14)
The invention discloses a compound containing a bipyrazole ring, and an intermediate and application thereof. The invention provides the compound containing a bipyrazole ring, as shown in a formula Iwhich is described in the specification. The compound can be used as a ligand, is high in selectivity, and is suitable for the application range of amide in C-N coupling and the C-C coupling reactionof arylboronic acid and aryl chloride, especially coupling with aryl chloride.
Preparation method of compound containing bipyrazole ring and intermediate thereof
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Paragraph 0284-0286, (2020/05/14)
The invention discloses a preparation method of a compound containing a bipyrazole ring and an intermediate of the compound. The preparation method of a bipyrazole ring-containing compound as shown ina formula I comprises the following steps: (1) adding alkali into a mixture of a bipyrazole ring compound as shown in a formula I-1 and a solvent for replacement reaction to obtain a mixed system; and (2) adding an organic phosphorus compound shown as a formula I-2 into the mixed system in the step (1), and carrying out a phosphonation reaction shown in the specification, so as to obtain the bipyrazole ring-containing compound shown as the formula I, wherein R1 and R2 are independently a C1-C6 alkyl group, a C3-C8 cycloalkyl group and a phenyl group, R3 is a C1-C6 alkyl group, and X is halogen. The prepared compound containing a bipyrazole ring can be used as a ligand, and is suitable for the application range of amide in C-N coupling and the C-C coupling reaction of arylboronic acid andaryl chloride.
Switching from biaryl formation to amidation with convoluted polymeric nickel catalysis
Sen, Abhijit,Dhital, Raghu N.,Sato, Takuma,Ohno, Aya,Yamada, Yoichi M.A.
, p. 14410 - 14418 (2020/12/21)
A stable, reusable, and insoluble poly(4-vinyl-pyridine) nickel catalyst (P4VP-NiCl2) was prepared through the molecular convolution of poly(4-vinylpyridine) (P4VP) and nickel chloride. We proposed a coordination structure of the Ni center in the precatalyst based on elemental analysis and Ni K-edge XANES, and we confirmed that it is consistent with Ni K-edge EXAFS. The Suzuki?Miyaura-type coupling of aryl halides and arylboronic esters proceeded using P4VP-NiCl2 (0.1 mol % Ni) to give the corresponding biaryl compounds in up to 94% yield. Surprisingly, when the same reaction of aryl halides and arylboronic acid/ester was carried out in the presence of amides, the amidation proceeded predominantly to give the corresponding arylamides in up to 99% yield. In contrast, the reaction of aryl halides and amides in the absence of arylboronic acid/ester did not proceed. P4VP-NiCl2 successfully catalyzed the lactamization for preparing phenanthridinone. P4VP-NiCl2 was reused five times without significant loss of catalytic activity. Pharmaceuticals, natural products, and biologically active compounds were synthesized efficiently using P4VPNiCl2 catalysis. Nickel contamination in the prepared pharmaceutical compounds was not detected by ICP-MS analysis. The reaction was scaled to multigrams without any loss of chemical yield. Mechanistic studies for both Suzuki?Miyaura and amidation were performed.
Clickable coupling of carboxylic acids and amines at room temperature mediated by SO2F2: A significant breakthrough for the construction of amides and peptide linkages
Wang, Shi-Meng,Zhao, Chuang,Zhang, Xu,Qin, Hua-Li
, p. 4087 - 4101 (2019/04/30)
The construction of amide bonds and peptide linkages is one of the most fundamental transformations in all life processes and organic synthesis. The synthesis of structurally ubiquitous amide motifs is essential in the assembly of numerous important molecules such as peptides, proteins, alkaloids, pharmaceutical agents, polymers, ligands and agrochemicals. A method of SO2F2-mediated direct clickable coupling of carboxylic acids with amines was developed for the synthesis of a broad scope of amides in a simple, mild, highly efficient, robust and practical manner (>110 examples, >90% yields in most cases). The direct click reactions of acids and amines on a gram scale are also demonstrated using an extremely easy work-up and purification process of washing with 1 M aqueous HCl to provide the desired amides in greater than 99% purity and excellent yields.
Optimization of Synthetically Versatile Pyridylidene Amide Ligands for Efficient Iridium-Catalyzed Water Oxidation
Navarro, Miquel,Smith, Christene A.,Li, Mo,Bernhard, Stefan,Albrecht, Martin
, p. 6386 - 6398 (2018/04/30)
The synthetic versatility of pyridylidene amide (PYA) ligands has been exploited to prepare and evaluate a diverging series of iridium complexes containing C,N-bidentate chelating aryl-PYA ligands for water oxidation catalysis. The phenyl-PYA lead structu
