A new fluorinated azidoethane─1-azido-1,1,2,2-tetrafluoroethane─was prepared in quantitative yield by the addition of an azide anion to tetrafluoroethylene in a protic medium. The title azide was shown to be thermally stable and insensitive to impact. Copper(I)-catalyzed [3 + 2] cycloaddition with alkynes afforded 4-substituted N-tetrafluoroethyl-1,2,3-triazoles which underwent rhodium(II)-catalyzed transannulation with nitriles to novel N-tetrafluoroethylimidazoles or the reaction with triflic acid to enamido triflates. [3 + 2] Cycloaddition of the title azide with primary amines afforded novel 5-difluoromethyl tetrazoles.

5 P Kukhar Institute of Bioorganic Chemistry and Petrochemistry The National Academy of Sciences of Ukraine Academika Kukhara Str 1 02094 Kyiv Ukraine

CF Plus Chemicals Karásek 1767 1 621 00 Brno Czech Republic

Institute of Energetic Materials Faculty of Chemical Technology University of Pardubice Doubravice 41 532 10 Pardubice Czech Republic

Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences Flemingovo Náměstí 2 166 10 Prague 6 Czech Republic

Zobrazit více v PubMed

Kirsch P.Perfluoroalkylation. In Modern Fluoroorganic Chemistry; Wiley-VCH Verlag GmbH & Co. KGaA: Weinheim, Germany, 2013; pp 107–167.

Reddy V. P.Organofluorine Compounds in Biology and Medicine; Elsevier, 2015; pp 1–312.

Gouverneur V.; Müller K.. Fluorine in Pharmaceutical and Medicinal Chemistry : From Biophysical Aspects to Clinical Applications; Imperial College Press, 2012; p 546.

Ojima I.Fluorine in Medicinal Chemistry and Chemical Biology; Wiley, 2009; pp 1–624.

Zhou Y.; Wang J.; Gu Z.; Wang S.; Zhu W.; Acena J. L.; Soloshonok V. A.; Izawa K.; Liu H. Next Generation of Fluorine-Containing Pharmaceuticals, Compounds Currently in Phase II-III Clinical Trials of Major Pharmaceutical Companies: New Structural Trends and Therapeutic Areas. Chem. Rev. 2016, 116, 422–518. 10.1021/acs.chemrev.5b00392. PubMed DOI

Gillis E. P.; Eastman K. J.; Hill M. D.; Donnelly D. J.; Meanwell N. A. Applications of Fluorine in Medicinal Chemistry. J. Med. Chem. 2015, 58, 8315–8359. 10.1021/acs.jmedchem.5b00258. PubMed DOI

Wang J.; Sánchez-Roselló M.; Aceña J. L.; Del Pozo C.; Sorochinsky A. E.; Fustero S.; Soloshonok V. A.; Liu H. Fluorine in Pharmaceutical Industry: Fluorine-Containing Drugs Introduced to the Market in the Last Decade (2001–2011). Chem. Rev. 2014, 114, 2432–2506. 10.1021/cr4002879. PubMed DOI

New Drugs at FDA: CDER’s New Molecular Entities and New Therapeutic Biological Products. https://www.fda.gov/drugs/development-approval-process-drugs/new-drugs-fda-cders-new-molecular-entities-and-new-therapeutic-biological-products (accessed 2023-06-01).

Wang Q.; Song H.; Wang Q. Fluorine-Containing Agrochemicals in the Last Decade and Approaches for Fluorine Incorporation. Chin. Chem. Lett. 2022, 33, 626–642. 10.1016/j.cclet.2021.07.064. DOI

Pazenok S.; Bernier D.; Donnard M.; Hanquet G.; Panossian A.; Leroux F. R. Modern Fluorine-Containing Agrochemicals. PATAI’S Chem. Funct. Groups 2022, 1–77. 10.1002/9780470682531.pat1013. DOI

Bakhanovich O.; Beier P. Synthesis, Stability and Reactivity of α-Fluorinated Azidoalkanes. Chem.—Eur. J. 2020, 26, 773–782. 10.1002/chem.201903627. PubMed DOI

Motornov V.; Markos A.; Beier P. A Rhodium-Catalyzed Transannulation of N-(per)Fluoroalkyl-1,2,3-Triazoles under Microwave Conditions - a General Route to N-(per)Fluoroalkyl-Substituted Five-Membered Heterocycles. Chem. Commun. 2018, 54, 3258–3261. 10.1039/C8CC01446A. PubMed DOI

Markos A.; Voltrova S.; Motornov V.; Tichý D.; Klepetářová B.; Beier P. Stereoselective Synthesis of (Z)-β-Enamido Triflates and Fluorosulfonates from N-Fluoroalkylated Triazoles. Chem.—Eur. J. 2019, 25, 7640–7644. 10.1002/chem.201901632. PubMed DOI

Markos A.; Janecký L.; Chvojka T.; Martinek T.; Martinez-Seara H.; Klepetářová B.; Beier P. Haloalkenyl Imidoyl Halides as Multifacial Substrates in the Stereoselective Synthesis of N-Alkenyl Compounds. Adv. Synth. Catal. 2021, 363, 3258–3266. 10.1002/adsc.202100009. DOI

Kubíčková A.; Markos A.; Voltrová S.; Marková A.; Filgas J.; Klepetářová B.; Slavíček P.; Beier P. Aza-Wolff Rearrangement of N-Fluoroalkyl Triazoles to Ketenimines. Org. Chem. Front. 2023, 10, 3201–3206. 10.1039/D3QO00618B. DOI

Václavík J.; Klimánková I.; Budinská A.; Beier P. Advances in the Synthesis and Application of Tetrafluoroethylene- and 1,1,2,2-Tetrafluoroethyl-Containing Compounds. Eur. J. Org Chem. 2018, 2018, 3554–3593. 10.1002/ejoc.201701590. DOI

Knunjanz I. L.; Bychowskaja E. G. Zhurnal Vsesoyuznogo Khimicheskogo Obschchestva im. D. I. Mendeleeva 1962, 7, 585–586.

Voltrová S.; Muselli M.; Filgas J.; Matoušek V.; Klepetářová B.; Beier P. Synthesis of tetrafluoroethylene- and tetrafluoroethyl-containing azides and their 1,3-dipolar cycloaddition as synthetic application. Org. Biomol. Chem. 2017, 15, 4962–4965. 10.1039/C7OB01151B. PubMed DOI

Krespan C. G.; Van-Catledge F. A.; Smart B. E. Generation and Capture of Functionalized Fluorocarbanions. J. Am. Chem. Soc. 1984, 106, 5544–5546. 10.1021/ja00331a024. DOI

Hercules D. A.; Parrish C. A.; Sayler T. S.; Tice K. T.; Williams S. M.; Lowery L. E.; Brady M. E.; Coward R. B.; Murphy J. A.; Hey T. A.; Scavuzzo A. R.; Rummler L. M.; Burns E. G.; Matsnev A. V.; Fernandez R. E.; McMillen C. D.; Thrasher J. S. Preparation of Tetrafluoroethylene from the Pyrolysis of Pentafluoropropionate Salts. J. Fluorine Chem. 2017, 196, 107–116. 10.1016/j.jfluchem.2016.10.004. DOI

Zhang L.; Zhang J.; Yang W.; Wang Y.; Fuβ W.; Weizbauer S. Highly Selective Photochemical Synthesis of Perfluoroalkyl Bromides and Iodides. J. Fluorine Chem. 1998, 88, 153–168. 10.1016/S0022-1139(98)00112-2. DOI

Hunadi R.; Baum K. Tetrafluoroethylene: A Convenient Laboratory preparation. Synthesis 1982, 1982, 454. 10.1055/s-1982-29830. DOI

Wang F.; Luo T.; Hu J.; Wang Y.; Krishnan H. S.; Jog P. V.; Ganesh S. K.; Prakash G. K. S.; Olah G. A. Synthesis of Gem-Difluorinated Cyclopropanes and Cyclopropenes: Trifluoromethyltrimethylsilane as a Difluorocarbene Source. Angew. Chem., Int. Ed. 2011, 50, 7153–7157. 10.1002/anie.201101691. PubMed DOI

Li L.; Ni C.; Xie Q.; Hu M.; Wang F.; Hu J. TMSCF PubMed DOI

Jankovič D.; Virant M.; Gazvoda M. Copper-Catalyzed Azide-Alkyne Cycloaddition of Hydrazoic Acid Formed in Situ from Sodium Azide Affords 4-Monosubstituted-1,2,3-Triazoles. J. Org. Chem. 2022, 87, 4018–4028. 10.1021/acs.joc.1c02775. PubMed DOI PMC

Blastik Z. E.; Voltrová S.; Matoušek V.; Jurásek B.; Manley D. W.; Klepetářová B.; Beier P. Azidoperfluoroalkanes: Synthesis and Application in Copper(I)-Catalyzed Azide-Alkyne Cycloaddition. Angew. Chem., Int. Ed. 2017, 56, 346–349. 10.1002/anie.201609715. PubMed DOI

Chopra P. N.; Sahu J. K. Biological Significance of Imidazole-Based Analogues in New Drug Development. Curr. Drug Discovery Technol. 2020, 17, 574–584. 10.2174/1570163816666190320123340. PubMed DOI

Mumtaz A.; Saeed A.; Fatima N.; Dawood M.; Rafique H.; Iqbal J. Imidazole and Its Derivatives as Potential Candidates for Drug Development. Bangladesh J. Pharmacol. 2016, 11, 756–764. 10.3329/bjp.v11i4.26835. DOI

Budinská A.; Václavík J.; Matoušek V.; Beier P. Nucleophilic Tetrafluoroethylation Employing in Situ Formed Organomagnesium Reagents. Org. Lett. 2016, 18, 5844–5847. 10.1021/acs.orglett.6b02890. PubMed DOI

Poludnenko V. G.; Didinskaya O. B.; Pozharskii A. F. Fluorine-Containing Azoles. 3. Reaction of Imidazoles and Perimidines with Perfluoroalkenes. Chem. Heterocycl. Compd. 1984, 20, 426–430. 10.1007/BF00513861. DOI

Polivanova A. G.; Shkavrov S. V.; Churakov A. V.; Lermontov A. S.; Lermontov S. A. A Novel Synthesis of 1,5-Disubstituted Fluorinated Tetrazoles from 1,1-Difluoroazides. Tetrahedron Lett. 2010, 51, 4205–4207. 10.1016/j.tetlet.2010.06.016. DOI

Neochoritis C. G.; Zhao T.; Dömling A. Tetrazoles via Multicomponent Reactions. Chem. Rev. 2019, 119, 1970–2042. 10.1021/acs.chemrev.8b00564. PubMed DOI PMC

Sarvary A.; Maleki A. A Review of Syntheses of 1,5-Disubstituted Tetrazole Derivatives. Mol. Diversity 2015, 19, 189–212. 10.1007/s11030-014-9553-3. PubMed DOI

Tanimoto H.; Kakiuchi K. Recent Applications and Developments of Organic Azides in Total Synthesis of Natural Products. Nat. Prod. Commun. 2013, 8, 1021-1034. 10.1177/1934578x1300800730. PubMed DOI

Wang J.; Horwitz M. A.; Dürr A. B.; Ibba F.; Pupo G.; Gao Y.; Ricci P.; Christensen K. E.; Pathak T. P.; Claridge T. D. W.; Lloyd-Jones G. C.; Paton R. S.; Gouverneur V. Asymmetric Azidation under Hydrogen Bonding Phase-Transfer Catalysis: A Combined Experimental and Computational Study. J. Am. Chem. Soc. 2022, 144, 4572–4584. 10.1021/jacs.1c13434. PubMed DOI PMC

Tichý D.; Košt́ál V.; Motornov V.; Klimánková I.; Beier P. Preparation of 1-Azido-2-Bromo-1,1,2,2-Tetrafluoroethane and Its Use in the Synthesis of N-Fluoroalkylated Nitrogen Heterocycles. J. Org. Chem. 2020, 85, 11482–11489. 10.1021/acs.joc.0c01610. PubMed DOI

Reactivity of 2H-Azirines in Copper-Catalyzed Azide-Alkyne Cycloaddition Reactions

Transformation of 5-acylated N-fluoroalkyl-1,2,3-triazoles to trifluoromethylated ring-fused isoquinolines, 1,3-oxazines, and 1,3-oxazin-6-ones via ketenimines

Lewis acid-mediated transformations of 5-acyl-N-fluoroalkyl-1,2,3-triazoles to cyclopentenones, indenones, or oxazoles