20157-44-2Relevant academic research and scientific papers
Aromatic C-H Methylation and Other Functionalizations via the Rh(III)-Catalyzed Migratory Insertion of Bis(phenylsulfonyl)carbene and Subsequent Transformations
Chen, Lei,Peng, Rui-Jun,Zhang, Xue-Jing,Yan, Ming,Chan, Albert S. C.
, p. 10177 - 10189 (2021/07/28)
The Rh(III)-catalyzed migratory insertion of bis(phenylsulfonyl)carbene into aromatic C-H bonds has been developed. A variety of bis(phenylsulfonyl)methyl derivatives were prepared with good yields under mild conditions. The methylated products were readily obtained after reductive desulfonylation. Furthermore, the diverse transformations of bis(phenylsulfonyl)methyl to trideuteriomethyl, aldehyde, and other functional groups were demonstrated.
Mechanochemical Solvent-Free Catalytic C?H Methylation
Ni, Shengjun,Hribersek, Matic,Baddigam, Swarna K.,Ingner, Fredric J. L.,Orthaber, Andreas,Gates, Paul J.,Pilarski, Lukasz T.
supporting information, p. 6660 - 6666 (2020/12/18)
The mechanochemical, solvent-free, highly regioselective, rhodium-catalyzed C?H methylation of (hetero)arenes is reported. The reaction shows excellent functional-group compatibility and is demonstrated to work for the late-stage C?H methylation of biologically active compounds. The method requires no external heating and benefits from considerably shorter reaction times than previous solution-based C?H methylation protocols. Additionally, the mechanochemical approach is shown to enable the efficient synthesis of organometallic complexes that are difficult to generate conventionally.
Cobalt-catalysed C–H methylation for late-stage drug diversification
Ackermann, Lutz,Friis, Stig D.,Johansson, Magnus J.
, p. 511 - 519 (2020/06/05)
The magic methyl effect is well acknowledged in medicinal chemistry, but despite its significance, accessing such analogues via derivatization at a late stage remains a pivotal challenge. In an effort to mitigate this major limitation, we here present a strategy for the cobalt-catalysed late-stage C–H methylation of structurally complex drug molecules. Enabling broad applicability, the transformation relies on a boron-based methyl source and takes advantage of inherently present functional groups to guide the C–H activation. The relative reactivity observed for distinct classes of functionalities were determined and the sensitivity of the transformation towards a panel of common functional motifs was tested under various reaction conditions. Without the need for prefunctionalization or postdeprotection, a diverse array of marketed drug molecules and natural products could be methylated in a predictable manner. Subsequent physicochemical and biological testing confirmed the magnitude with which this seemingly minor structural change can affect important drug properties. [Figure not available: see fulltext.]
Nucleophilic aromatic substitution of unactivated fluoroarenes enabled by organic photoredox catalysis
Nicewicz, David A.,Pistritto, Vincent A.,Schutzbach-Horton, Megan E.
supporting information, p. 17187 - 17194 (2020/11/02)
Nucleophilic aromatic substitution (SNAr) is a classical reaction with well-known reactivity toward electron-poor fluoroarenes. However, electron-neutral and electron-rich fluoro(hetero)arenes are considerably underrepresented. Herein, we present a method for the nucleophilic defluorination of unactivated fluoroarenes enabled by cation radical-accelerated nucleophilic aromatic substitution. The use of organic photoredox catalysis renders this method operationally simple under mild conditions and is amenable to various nucleophile classes, including azoles, amines, and carboxylic acids. Select fluorinated heterocycles can be functionalized using this method. In addition, the late-stage functionalization of pharmaceuticals is also presented. Computational studies demonstrate that the site selectivity of the reaction is dictated by arene electronics.
Manganese-catalyzed directed methylation of C(sp2)-H bonds at 25 °C with high catalytic turnover
Sato, Takenari,Yoshida, Takumi,Al Mamari, Hamad H.,Ilies, Laurean,Nakamura, Eiichi
supporting information, p. 5458 - 5461 (2017/11/06)
We report here a manganese-catalyzed C-H methylation reaction of considerable substrate scope, using MeMgBr, a catalytic amount of MnCl2· 2LiCl, and an organic dihalide oxidant. The reaction features ambient temperature, low catalyst loading, typically 1%, high catalytic turnover reaching 5.9 × 103, and no need for an extraneous ligand and illustrates a unique catalytic use of simple manganese salts for C-H activation, which so far has relied on catalysis by manganese carbonyls.
A N - aryl pyrazole compounds and N - aryl imidazole compound of preparation method
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Paragraph 0050; 0051; 0052; 0053; 0054; 0055, (2017/10/05)
The invention discloses a preparation method of an N-arylpyrazole compound and an N-arylimidazole compound. The method comprises the following steps: reacting at 20-120 DEG C for 6-48 hours by taking aryl halide and pyrazole or imidazole as substrates and copper salt as a catalyst in an organic solvent in the presence of alkali and a nitrogenous ligand under nitrogen protection; and after the reaction is finished, separating and purifying a reaction liquid to obtain the N-arylpyrazole compound or the N-arylimidazole compound. A product prepared by utilizing the method disclosed by the invention can not only be directly used, but also be used for other reactions as a substrate and has the advantages of moderation in adopted reaction condition, simple operation step and post-processing process, high yield and suitability for large-scale production.
3-(Diphenylphosphino)propanoic acid: An efficient ligand for the Cu-catalyzed N-arylation of imidazoles and 1H-pyrazole with aryl halides
Liu, Ya-Shuai,Liu, Yan,Ma, Xiao-Wei,Liu, Ping,Xie, Jian-Wei,Dai, Bin
, p. 775 - 778 (2014/06/09)
3-(Diphenylphosphino)propanoic acid (L2) has proved to be an efficient ligand for the copper-catalyzed CN coupling reactions. N-arylation of imidazoles with aryl iodides catalyzed by CuCl/L2 was smoothly carried out in DMSO at 100 °C with a yield up to 98%. N-arylation of 1H-pyrazole with aryl iodides and bromides catalyzed by Cu(OAc)2/L2 in 1,4-dioxane also gave the corresponding products with yields of 40%-98%.
Copper-catalyzed arylation of nitrogen heterocycles from anilines under ligand-free conditions
Toummini, Dounia,Tlili, Anis,Bergs, Julien,Ouazzani, Fouad,Taillefer, Marc
supporting information, p. 14619 - 14623 (2015/01/09)
The arylation of pyrazole and derivatives can be achieved by coupling arenediazonium species (formed in situ from anilines) by using a catalytic system that employs low-toxicity and inexpensive copper metal under very mild and ligand-free conditions (T = 20 ° C). From other nitrogen heterocycles, the presence of an additive (NBu4I) significantly improves the efficiency of the catalytic system. These results represent the first examples of C-N bond formation from arenediazonium species.
Ruthenium-catalyzed c-h silylation of 1-arylpyrazole derivatives and fluoride-mediated carboxylation: Use of two nitrogen atoms of the pyrazole Group
Mita, Tsuyoshi,Tanaka, Hiroyuki,Michigami, Kenichi,Sato, Yoshihiro
supporting information, p. 1291 - 1294 (2014/06/10)
Carboxylation of 1-arylpyrazole derivatives was developed using a ruthenium-catalyzed ortho silylation in conjunction with fluoride-mediated carboxylation with carbon dioxide. The two nitrogen atoms of pyrazole play crucial roles in promoting ortho silylation via the formation of a five-membered ruthenacycle and in accelerating aryl anion formation by lowering the electron density of the aromatic ring. Georg Thieme Verlag Stuttgart New York.
N-arylation of heterocycles catalyzed by activated-copper in pure water
Yang, Qichao,Wang, Yufang,Lin, Dong,Zhang, Mingjie
supporting information, p. 1994 - 1997 (2013/04/10)
N-arylation Activated-copper powder is an efficient catalyst for the N-arylation of heterocycles with aryl halides and can be reused several times. The reactions can proceed smoothly in water by using LiOH as base and give the corresponding products in good yields. The protocol shows good tolerance toward various functional groups.
