Monofluoromethylation of N-Heterocyclic Compounds

被引:0
作者
Moskalik, Mikhail Yu. [1 ]
机构
[1] Russian Acad Sci, AE Favorsky Irkutsk Inst Chem, Siberian Div, 1 Favorsky St, Irkutsk 664033, Russia
基金
英国科研创新办公室;
关键词
fluorine; fluoromethylation; nitrogen heterocyles; fluorination; pyrrolidines; imidazoles; indoles; pyridines; quinalines; pyridazines; ELECTROPHILIC MONOFLUOROMETHYLATION; NUCLEOPHILES; HYPOXIA; DRUGS; PET;
D O I
10.3390/ijms242417593
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The review focuses on recent advances in the methodologies for the formation or introduction of the CH2F moiety in N-heterocyclic substrates over the past 5 years. The monofluoromethyl group is one of the most versatile fluorinated groups used to modify the properties of molecules in synthetic medical chemistry. The review summarizes two strategies for the monofluoromethylation of N-containing heterocycles: direct monofluoromethylation with simple XCH2F sources (for example, ICH2F) and the assembly of N-heterocyclic structures from CH2F-containing substrates. The review describes the monofluoromethylation of pharmaceutically important three-, five- and six-membered N-heterocycles: pyrrolidines, pyrroles, indoles, imidazoles, triazoles, benzothiazoles, carbazoles, indazoles, pyrazoles, oxazoles, piperidines, morpholines, pyridines, quinolines and pyridazines. Assembling of 6-fluoromethylphenanthridine, 5-fluoromethyl-2-oxazolines, C5-monofluorinated isoxazoline N-oxides, and alpha-fluoromethyl-alpha-trifluoromethylaziridines is also shown. Fluoriodo-, fluorchloro- and fluorbromomethane, FCH2SO2Cl, monofluoromethyl(aryl)sulfoniummethylides, monofluoromethyl sulfides, (fluoromethyl)triphenylphosphonium iodide and 2-fluoroacetic acid are the main fluoromethylating reagents in recent works. The replacement of atoms and entire functional groups with a fluorine atom(s) leads to a change and often improvement in activity, chemical or biostability, and pharmacokinetic properties. The monofluoromethyl group is a bioisoster of -CH3, -CH2OH, -CH2NH2, -CH2CH3, -CH2NO2 and -CH2SH moieties. Bioisosteric replacement with the CH2F group is both an interesting task for organic synthesis and a pathway to modify drugs, agrochemicals and useful intermediates.
引用
收藏
页数:24
相关论文
共 50 条
  • [31] Application of silver N-heterocyclic carbene complexes in O-glycosidation reactions
    Talisman, Ian J.
    Kumar, Vineet
    Deschamps, Jeffrey R.
    Frisch, Mark
    Malhotra, Sanjay V.
    CARBOHYDRATE RESEARCH, 2011, 346 (15) : 2337 - 2341
  • [32] Modular synthesis of α-aryl β-perfluoroalkyl ketones via N-heterocyclic carbene catalysis
    Yang, Hai-Bin
    Wang, Zhi-Hou
    Li, Jin-Mei
    Wu, Chuande
    CHEMICAL COMMUNICATIONS, 2020, 56 (26) : 3801 - 3804
  • [33] Pd(H)-Catalyzed C-H Amination for N-Heterocyclic Synthesis
    Jeong, Eun Joo
    Youn, So Won
    BULLETIN OF THE KOREAN CHEMICAL SOCIETY, 2014, 35 (09) : 2611 - 2612
  • [34] Stereoselective Fluoroalkylacylation of Alkynes via Cooperative N-Heterocyclic Carbene/Palladium Catalysis
    Huang, Ying
    Wang, Xin-Han
    Zhang, Chun-Lin
    Ye, Song
    ORGANIC LETTERS, 2024, 26 (16) : 3441 - 3446
  • [35] Activation of SF5CF3 by the N-Heterocyclic Carbene SIMes
    Herbstritt, Domenique
    Tomar, Pooja
    Braun, Thomas
    MOLECULES, 2023, 28 (18):
  • [36] N-Heterocyclic carbenes via abstraction of ammonia: 'normal' carbenes with 'abnormal' character
    Schaper, Lars-Arne
    Oefele, Karl
    Kadyrov, Renat
    Bechlars, Bettina
    Drees, Markus
    Cokoja, Mirza
    Herrmann, Wolfgang A.
    Kuehn, Fritz E.
    CHEMICAL COMMUNICATIONS, 2012, 48 (32) : 3857 - 3859
  • [37] Oxidative Enantioselective α-Fluorination of Aliphatic Aldehydes Enabled by N-Heterocyclic Carbene Catalysis
    Li, Fangyi
    Wu, Zijun
    Wang, Jian
    ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2015, 54 (02) : 656 - 659
  • [38] Atom economical coupling of benzophenone and N-heterocyclic aromatics with SmI2
    Jaoul, Arnaud
    Yang, Yan
    Casaretto, Nicolas
    Clavaguera, Carine
    Maron, Laurent
    Nocton, Gregory
    CHEMICAL COMMUNICATIONS, 2020, 56 (79) : 11875 - 11878
  • [39] Saturated N-Heterocyclic Carbene Based Thiele's Hydrocarbon with a Tetrafluorophenylene Linker
    Kundu, Gargi
    De, Sriman
    Tothadi, Srinu
    Das, Abhishek
    Koley, Debasis
    Sen, Sakya S.
    CHEMISTRY-A EUROPEAN JOURNAL, 2019, 25 (72) : 16533 - 16537
  • [40] Synthetic routes to N-heterocyclic carbene complexes: Pyridine-carbene tautomerizations
    Kunz, Doris
    ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2007, 46 (19) : 3405 - 3408