402-43-7Relevant articles and documents
Synthesis of ArCF2X and [18F]Ar-CF3via Cleavage of the Trifluoromethylsulfonyl Group
Gao, Xinyan,Gong, Kehao,Han, Junbin,Wang, Juan,Wang, Mingwei,Xu, Bo,Yang, Ren-Yin,Zeng, Xiaojun
, (2021/12/17)
A versatile synthesis of ArCF2X and [18F]Ar-CF3 type compounds from readily available ArCF2SO2CF3 has been developed. Diverse nucleophiles, including weak nucleophiles such as halides (18F-, Cl-, Br-, and I-), RSH, and ROH, could react with ArCF2SO2CF3 efficiently to give the corresponding difluoromethylene products. The control experiments and the Hammett plot indicated that the reaction might proceed through a difluorocarbocation intermediate generated from the steric hindrance-assisted cleavage of the trifluoromethylsulfonyl group.
Preparation method of perfluoroalkylated aryl compound
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Paragraph 0100-0103, (2021/11/14)
The present invention provides a process for the preparation of a perfluoroalkylated aryl compound which comprises reacting an aryl compound with a perfluoroalkylsulfinate in the presence of an iron salt and hydrogen peroxide. To the method provided by the invention, perfluoroalkyl sulfinate is used as an alkylating agent, iron salt is used as a catalyst, hydrogen peroxide is used as an initiator, and the reaction time is short. The method has the characteristics of high yield, convenient operation, high safety and the like, and has wide application in the fields of drug synthesis, biological probes, fluorescent materials and the like.
Cross-Coupling through Ag(I)/Ag(III) Redox Manifold
Demonti, Luca,Mézailles, Nicolas,Nebra, Noel,Saffon-Merceron, Nathalie
supporting information, p. 15396 - 15405 (2021/10/12)
In ample variety of transformations, the presence of silver as an additive or co-catalyst is believed to be innocuous for the efficiency of the operating metal catalyst. Even though Ag additives are required often as coupling partners, oxidants or halide scavengers, its role as a catalytically competent species is widely neglected in cross-coupling reactions. Most likely, this is due to the erroneously assumed incapacity of Ag to undergo 2e? redox steps. Definite proof is herein provided for the required elementary steps to accomplish the oxidative trifluoromethylation of arenes through AgI/AgIII redox catalysis (i. e. CEL coupling), namely: i) easy AgI/AgIII 2e? oxidation mediated by air; ii) bpy/phen ligation to AgIII; iii) boron-to-AgIII aryl transfer; and iv) ulterior reductive elimination of benzotrifluorides from an [aryl-AgIII-CF3] fragment. More precisely, an ultimate entry and full characterization of organosilver(III) compounds [K]+[AgIII(CF3)4]? (K-1), [(bpy)AgIII(CF3)3] (2) and [(phen)AgIII(CF3)3] (3), is described. The utility of 3 in cross-coupling has been showcased unambiguously, and a large variety of arylboron compounds was trifluoromethylated via [AgIII(aryl)(CF3)3]? intermediates. This work breaks with old stereotypes and misconceptions regarding the inability of Ag to undergo cross-coupling by itself.
Metal- and base-free synthesis of aryl bromides from arylhydrazines
Phuc Tran, Dat,Nomoto, Akihiro,Mita, Soichiro,Dong, Chun-ping,Kodama, Shintaro,Mizuno, Takumi,Ogawa, Akiya
supporting information, (2020/05/08)
An efficient method was developed to synthesize brominated aromatic compounds from arylhydrazine hydrochlorides by using BBr3 in DMSO/CPME (cyclopentyl methyl ether) under air at 80 °C for 1 h without the use of bases or metal catalysts. In particular, this method could be carried out satisfactorily using electron-withdrawing groups to afford aryl bromides in a moderate to excellent yields.
Base-catalyzed aryl halide isomerization enables the 4-selective substitution of 3-bromopyridines
Bandar, Jeffrey S.,Puleo, Thomas R.
, p. 10517 - 10522 (2020/10/18)
The base-catalyzed isomerization of simple aryl halides is presented and utilized to achieve the 4-selective etherification, hydroxylation and amination of 3-bromopyridines. Mechanistic studies support isomerization of 3-bromopyridines to 4-bromopyridines proceedsviapyridyne intermediates and that 4-substitution selectivity is driven by a facile aromatic substitution reaction. Useful features of a tandem aryl halide isomerization/selective interception approach to aromatic functionalization are demonstrated. Example benefits include the use of readily available and stable 3-bromopyridines in place of less available and stable 4-halogenated congeners and the ability to converge mixtures of 3- and 5-bromopyridines to a single 4-substituted product.
Deoxyfluorination of acyl fluorides to trifluoromethyl compounds by FLUOLEAD/Olah's reagent under solvent-free conditions
Liang, Yumeng,Taya, Akihito,Zhao, Zhengyu,Saito, Norimichi,Shibata, Norio
, p. 3052 - 3058 (2021/01/15)
A new protocol enabling the formation of trifluoromethyl compounds from acyl fluorides has been developed. The combination of FLUOLEAD and Olah's reagent in solvent-free conditions at 70 °C initiated the significant deoxyfluorination of the acyl fluorides and resulted in the corresponding trifluoromethyl products with high yields (up to 99%). This strategy showed a great tolerance for various acyl fluorides containing aryloyl, (heteroaryl)oyl, or aliphatic acyl moieties, providing good to excellent yields of the trifluoromethyl products. Synthetic drug-like molecules were also transformed into the corresponding trifluoromethyl compounds under the same reaction conditions. A reaction mechanism is proposed.
Cathodic C-H Trifluoromethylation of Arenes and Heteroarenes Enabled by an in Situ-Generated Triflyltriethylammonium Complex
Cantillo, David,Jud, Wolfgang,Kappe, C. Oliver,Maljuric, Snjezana
supporting information, (2019/10/08)
While several trifluoromethylation reactions involving the electrochemical generation of CF3 radicals via anodic oxidation have been reported, the alternative cathodic, reductive radical generation has remained elusive. Herein, the first cathodic trifluoromethylation of arenes and heteroarenes is reported. The method is based on the electrochemical reduction of an unstable triflyltriethylammonium complex generated in situ from inexpensive triflyl chloride and triethylamine, which produces CF3 radicals that are trapped by the arenes on the cathode surface.
Aryl Sulfonium Salts for Site-Selective Late-Stage Trifluoromethylation
Ye, Fei,Berger, Florian,Jia, Hao,Ford, Joseph,Wortman, Alan,B?rgel, Jonas,Genicot, Christophe,Ritter, Tobias
, p. 14615 - 14619 (2019/09/17)
Incorporation of the CF3 group into arenes has found increasing importance in drug discovery. Herein, we report the first photoredox-catalyzed cross-coupling of aryl thianthrenium salts with a copper-based trifluoromethyl reagent, which enables a site-selective late-stage trifluoromethylation of arenes. The reaction proceeds with broad functional group tolerance, even for complex small molecules on gram scale. The method was further extended to produce pentafluoroethylated derivatives.
Mechanism of Photoredox-Initiated C-C and C-N Bond Formation by Arylation of IPrAu(I)-CF3 and IPrAu(I)-Succinimide
Kim, Suhong,Toste, F. Dean
, p. 4308 - 4315 (2019/01/25)
Herein, we report on the photoredox-initiated gold-mediated C(sp2)-CF3 and C(sp2)-N coupling reactions. By adopting gold as a platform for probing metallaphotoredox catalysis, we demonstrate that cationic gold(III) complexes are the key intermediates of the C-C and C-N coupling reactions. The high-valent gold(III) intermediates are accessed by virtue of photoredox catalysis through a radical chain process. In addition, the bond-forming step of the coupling reactions is the reductive elimination from cationic gold(III) intermediates, which is supported by isolation and crystallographic characterization of key Au(III) intermediates.
Synthesis of plasmodione metabolites and 13C-enriched plasmodione as chemical tools for drug metabolism investigation
Feng, Liwen,Lanfranchi, Don Antoine,Cotos, Leandro,Cesar-Rodo, Elena,Ehrhardt, Katharina,Goetz, Alice-Anne,Zimmermann, Herbert,Fenaille, Fran?ois,Blandin, Stephanie A.,Davioud-Charvet, Elisabeth
, p. 2647 - 2665 (2018/04/27)
Malaria is a tropical parasitic disease threatening populations in tropical and sub-tropical areas. Resistance to antimalarial drugs has spread all over the world in the past 50 years, thus new drugs are urgently needed. Plasmodione (benzylmenadione series) has been identified as a potent antimalarial early lead drug, acting through a redox bioactivation on asexual and young sexual blood stages. To investigate its metabolism, a series of plasmodione-based tools, including a fully 13C-labelled lead drug and putative metabolites, have been designed and synthesized for drug metabolism investigation. Furthermore, with the help of UHPLC-MS/MS, two of the drug metabolites have been identified from urine of drug-treated mice.
