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Current Organic Synthesis

Editor-in-Chief

ISSN (Print): 1570-1794
ISSN (Online): 1875-6271

Review Article

Recent Advancements in the Synthesis of α-fluoroalkylated Azine-derived Heterocycles through Direct Fluorination

Author(s): Oksana M. Shavrina, Yuliya V. Rassukana and Petro P. Onysko*

Volume 21, Issue 8, 2024

Published on: 02 November, 2023

Page: [1053 - 1074] Pages: 22

DOI: 10.2174/0115701794271650231016094853

Price: $65

Abstract

The review highlights recent advancements in the synthesis of α-fluoro and α,α- difluoroalkylated azines, focusing on two main approaches. The first approach involves nucleophilic deoxofluorination, wherein α-hydroxy- or α-oxoalkylated azines are treated with diethylaminosulfur trifluoride or other S-F reagents to introduce fluorine atoms. The second approach employs direct electrophilic benzylic fluorination, whereby alkylazines undergo fluorination using N-F reagents. Both methods provide flexibility in designing and synthesizing fluoroalkylated heterocycles.

Graphical Abstract

[1]
Vitaku, E.; Smith, D.T.; Njardarson, J.T. Analysis of the structural diversity, substitution patterns, and frequency of nitrogen heterocycles among U.S. FDA approved pharmaceuticals. J. Med. Chem., 2014, 57(24), 10257-10274.
[http://dx.doi.org/10.1021/jm501100b] [PMID: 25255204]
[2]
Zafrani, Y.; Yeffet, D.; Sod-Moriah, G.; Berliner, A.; Amir, D.; Marciano, D.; Gershonov, E.; Saphier, S. Difluoromethyl bioisostere: Examining the “lipophilic hydrogen bond donor” concept. J. Med. Chem., 2017, 60(2), 797-804.
[http://dx.doi.org/10.1021/acs.jmedchem.6b01691] [PMID: 28051859]
[3]
Erickson, J.A.; McLoughlin, J.I. Hydrogen bond donor properties of the difluoromethyl group. J. Org. Chem., 1995, 60(6), 1626-1631.
[http://dx.doi.org/10.1021/jo00111a021]
[4]
Ashwood, M.S.; Alabaster, R.J.; Cottrell, I.F.; Cowden, C.J.; Davies, A.J.; Dolling, U.H.; Emerson, K.M.; Gibb, A.D.; Hands, D.; Wallace, D.J.; Wilson, R.D. Development of a scaleable synthesis of a 3-aminopyrazinone acetamide thrombin inhibitor. Org. Process Res. Dev., 2004, 8(2), 192-200.
[http://dx.doi.org/10.1021/op0341420]
[5]
Qian, A.; Zheng, Y.; Wang, R.; Wei, J.; Cui, Y.; Cao, X.; Yang, Y. Design, synthesis, and structure-activity relationship studies of novel tetrazole antifungal agents with potent activity, broad antifungal spectrum and high selectivity. Bioorg. Med. Chem. Lett., 2018, 28(3), 344-350.
[http://dx.doi.org/10.1016/j.bmcl.2017.12.040] [PMID: 29289430]
[6]
Han, J.; Remete, A.M.; Dobson, L.S.; Kiss, L.; Izawa, K.; Moriwaki, H.; Soloshonok, V.A.; O’Hagan, D. Next generation organofluorine containing blockbuster drugs. J. Fluor. Chem., 2020, 239, 109639.
[http://dx.doi.org/10.1016/j.jfluchem.2020.109639]
[7]
Gerullis, H.; Wawroschek, F.; Köhne, C.H.; Ecke, T.H. Vinflunine in the treatment of advanced urothelial cancer: Clinical evidence and experience. Ther. Adv. Urol., 2017, 9(1), 28-35.
[http://dx.doi.org/10.1177/1756287216677903] [PMID: 28042310]
[8]
Mederski, W.; Fuchss, T.; Zenke, F. Morpholinylquinazolines. U.S. Patent US20130012489, 2013.
[9]
Wustman, R.B.; Valenzano, K.; Boyd, R. Method for treating Alzheimer’s disease using pharmacological chaperones to increase the activity of gangliosidases. E.P. Patent 2957295, 2015.
[10]
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(4), 2432-2506.
[http://dx.doi.org/10.1021/cr4002879] [PMID: 24299176]
[11]
Inoue, M.; Sumii, Y.; Shibata, N. Contribution of organofluorine compounds to pharmaceuticals. ACS Omega, 2020, 5(19), 10633-10640.
[http://dx.doi.org/10.1021/acsomega.0c00830] [PMID: 32455181]
[12]
(a) Szpera, R.; Moseley, D.F.J.; Smith, L.B.; Sterling, A.J.; Gouverneur, V. The fluorination of C−H bonds: Developments and perspectives. Angew. Chem. Int. Ed., 2019, 58(42), 14824-14848.
[http://dx.doi.org/10.1002/anie.201814457] [PMID: 30759327];
(b) Schubert, T.J.; Oboh, E.; Peek, H.; Philo, E.; Teixeira, J.E.; Stebbins, E.E.; Miller, P.; Oliva, J.; Sverdrup, F.M.; Griggs, D.W.; Huston, C.D.; Meyers, M.J. Structure–activity relationship studies of the aryl acetamide triazolopyridazines against cryptosporidium reveals remarkable role of fluorine. J. Med. Chem., 2023, 66(12), 7834-7848.
[http://dx.doi.org/10.1021/acs.jmedchem.3c00110] [PMID: 37267631]
[13]
Coe, P.L.; Harnden, M.R.; Jones, A.S.; Noble, S.A.; Walker, R.T. Synthesis and antiviral properties of some 2′-deoxy-5-(fluoroalkenyl)uridines. J. Med. Chem., 1982, 25(11), 1329-1334.
[http://dx.doi.org/10.1021/jm00353a011] [PMID: 6292425]
[14]
Lall, M.S.; Bassyouni, A.; Bradow, J.; Brown, M.; Bundesmann, M.; Chen, J.; Ciszewski, G.; Hagen, A.E.; Hyek, D.; Jenkinson, S.; Liu, B.; Obach, R.S.; Pan, S.; Reilly, U.; Sach, N.; Smaltz, D.J.; Spracklin, D.K.; Starr, J.; Wagenaar, M.; Walker, G.S. Late-stage lead diversification coupled with quantitative nuclear magnetic resonance spectroscopy to identify new structure–activity relationship vectors at nanomole-scale synthesis: Application to loratadine, a human histamine H 1 receptor inverse agonist. J. Med. Chem., 2020, 63(13), 7268-7292.
[http://dx.doi.org/10.1021/acs.jmedchem.0c00483] [PMID: 32462865]
[15]
Subota, A.I.; Ryabukhin, S.V.; Gorlova, A.O.; Grygorenko, O.O.; Volochnyuk, D.M. An approach to the synthesis of 3-substituted piperidines bearing partially fluorinated alkyl groups. J. Fluor. Chem., 2019, 224, 61-66.
[http://dx.doi.org/10.1016/j.jfluchem.2019.05.006]
[16]
Felts, A.S.; Rodriguez, A.L.; Morrison, R.D.; Blobaum, A.L.; Byers, F.W.; Daniels, J.S.; Niswender, C.M.; Conn, P.J.; Lindsley, C.W.; Emmitte, K.A. Discovery of 6-(pyrimidin-5-ylmethyl)quinoline-8-carboxamide negative allosteric modulators of metabotropic glutamate receptor subtype 5. Bioorg. Med. Chem. Lett., 2018, 28(10), 1679-1685.
[http://dx.doi.org/10.1016/j.bmcl.2018.04.053] [PMID: 29705142]
[17]
Medebielle, M.; Ait-Mohand, S.; Burkhloder, C.; Dolbier, W.R., Jr; Laumond, G.; Aubertin, A.M. Syntheses of new difluoromethylene benzoxazole and 1,2,4-oxadiazole derivatives, as potent non-nucleoside HIV-1 reverse transcriptase inhibitors. J. Fluor. Chem., 2005, 126(4), 533-540.
[http://dx.doi.org/10.1016/j.jfluchem.2004.12.016]
[18]
(a) Loksha, Y.M.; Pedersen, E.B.; Loddo, R.; Sanna, G.; Collu, G.; Giliberti, G.; Colla, P.L. Synthesis of novel fluoro analogues of MKC442 as microbicides. J. Med. Chem., 2014, 57(12), 5169-5178.
[http://dx.doi.org/10.1021/jm500139a] [PMID: 24805780];
(b) Loksha, Y.M.; Pedersen, E.B.; Loddo, R.; La Colla, P. Synthesis and anti-HIV-1 activity of 1-substiuted 6-(3-cyanobenzoyl) and [(3-cyanophenyl)fluoromethyl]-5-ethyl-uracils. Arch. Pharm., 2009, 342(9), 501-506.
[http://dx.doi.org/10.1002/ardp.200900058] [PMID: 19637180];
(c) Radi, M.; Angeli, L.; Franchi, L.; Contemori, L.; Maga, G.; Samuele, A.; Zanoli, S.; Armand-Ugon, M.; Gonzalez, E.; Llano, A.; Esté, J.A.; Botta, M. Towards novel S-DABOC inhibitors: Synthesis, biological investigation, and molecular modeling studies. Bioorg. Med. Chem. Lett., 2008, 18(21), 5777-5780.
[http://dx.doi.org/10.1016/j.bmcl.2008.09.070] [PMID: 18842407];
(d) Wang, P.; Felsing, D.E.; Chen, H.; Stutz, S.J.; Murphy, R.E.; Cunningham, K.A.; Allen, J.A.; Zhou, J. Discovery of potent and brain-penetrant gpr52 agonist that suppresses psychostimulant behavior. J. Med. Chem., 2020, 63(22), 13951-13972.
[http://dx.doi.org/10.1021/acs.jmedchem.0c01498] [PMID: 33198466]
[19]
Yoon, Y.A.; Park, C.S.; Cha, M.H.; Choi, H.; Sim, J.Y.; Kim, J.G. Novel pyrimidines as acid pump antagonists (APAs). Bioorg. Med. Chem. Lett., 2010, 20(19), 5735-5738.
[http://dx.doi.org/10.1016/j.bmcl.2010.08.007] [PMID: 20810280]
[20]
Pham, V.; Zhang, W.; Chen, V.; Whitney, T.; Yao, J.; Froese, D.; Friesen, A.D.; Diakur, J.M.; Haque, W. Design and synthesis of novel pyridoxine 5′-phosphonates as potential antiischemic agents. J. Med. Chem., 2003, 46(17), 3680-3687.
[http://dx.doi.org/10.1021/jm0300678] [PMID: 12904072]
[21]
Bannwarth, P.; Valleix, A.; Grée, D.; Grée, R. Flexible synthesis of pyrimidines with chiral monofluorinated and difluoromethyl side chains. J. Org. Chem., 2009, 74(12), 4646-4649.
[http://dx.doi.org/10.1021/jo900674u] [PMID: 19518154]
[22]
Blake, J.F.; Xu, R.; Bencsik, J.R.; Xiao, D.; Kallan, N.C.; Schlachter, S.; Mitchell, I.S.; Spencer, K.L.; Banka, A.L.; Wallace, E.M.; Gloor, S.L.; Martinson, M.; Woessner, R.D.; Vigers, G.P.A.; Brandhuber, B.J.; Liang, J.; Safina, B.S.; Li, J.; Zhang, B.; Chabot, C.; Do, S.; Lee, L.; Oeh, J.; Sampath, D.; Lee, B.B.; Lin, K.; Liederer, B.M.; Skelton, N.J. Discovery and preclinical pharmacology of a selective ATP-competitive Akt inhibitor (GDC-0068) for the treatment of human tumors. J. Med. Chem., 2012, 55(18), 8110-8127.
[http://dx.doi.org/10.1021/jm301024w] [PMID: 22934575]
[23]
Tanzer, E.M.; Schweizer, W.B.; Ebert, M.O.; Gilmour, R. Designing fluorinated cinchona alkaloids for enantioselective catalysis: Controlling internal rotation by a fluorine-ammonium ion gauche effect (φ(NCCF)). Chemistry, 2012, 18(7), 2006-2013.
[http://dx.doi.org/10.1002/chem.201102859] [PMID: 22250061]
[24]
Mondelli, C.; Bucher, C.; Baiker, A.; Gilmour, R. A novel class of fluorinated cinchona alkaloids as surface modifiers for the enantioselective heterogeneous hydrogenation of α-ketoesters. J. Mol. Catal. Chem., 2010, 327(1-2), 87-91.
[http://dx.doi.org/10.1016/j.molcata.2010.05.017]
[25]
Wang, X.; Zeng, Y.; Sheng, L.; Larson, P.; Liu, X.; Zou, X.; Wang, S.; Guo, K.; Ma, C.; Zhang, G.; Cui, H.; Ferguson, D.M.; Li, Y.; Zhang, J.; Aldrich, C.C. A cinchona alkaloid antibiotic that appears to target ATP synthase in streptococcus pneumoniae. J. Med. Chem., 2019, 62(5), 2305-2332.
[http://dx.doi.org/10.1021/acs.jmedchem.8b01353] [PMID: 30779564]
[26]
Bucher, C.; Sparr, C.; Schweizer, W.B.; Gilmour, R. Fluorinated quinine alkaloids: Synthesis, X-ray structure analysis and antimalarial parasite chemotherapy. Chemistry, 2009, 15(31), 7637-7647.
[http://dx.doi.org/10.1002/chem.200900505] [PMID: 19565586]
[27]
Schmeck, C.; Gielen-Haertwig, H.; Vakalopoulos, A.; Bischoff, H.; Li, V.; Wirtz, G.; Weber, O. Novel tetrahydrochinoline derived CETP inhibitors. Bioorg. Med. Chem. Lett., 2010, 20(5), 1740-1743.
[http://dx.doi.org/10.1016/j.bmcl.2010.01.071] [PMID: 20137927]
[28]
Lee, C.; Lai, J.; Epifanov, M.; Wang, C.X.; Sammis, G.M. Efficient protocol for the SO2F2-mediated deoxyfluorination of aliphatic alcohols. J. Fluor. Chem., 2021, 251, 109888.
[http://dx.doi.org/10.1016/j.jfluchem.2021.109888]
[29]
Zhang, Q.; Mixdorf, J.C.; Reynders, G.J., III; Nguyen, H.M. Rhodium-catalyzed benzylic fluorination of trichloroacetimidates. Tetrahedron, 2015, 71(35), 5932-5938.
[http://dx.doi.org/10.1016/j.tet.2015.04.066]
[30]
McTeague, T.A.; Jamison, T.F. Photoredox activation of SF 6 for fluorination. Angew. Chem. Int. Ed., 2016, 55(48), 15072-15075.
[http://dx.doi.org/10.1002/anie.201608792] [PMID: 27813242]
[31]
Haas, A.; Spitzer, M.; Lieb, M. Synthese seitenkettenfluorierter aromatischer verbindungen und deren chemische reaktivität. Chem. Ber., 1988, 121(7), 1329-1340.
[http://dx.doi.org/10.1002/cber.19881210718]
[32]
Trofymchuk, S.; Bugera, M.; Klipkov, A.A.; Ahunovych, V.; Razhyk, B.; Semenov, S.; Boretskyi, A.; Tarasenko, K.; Mykhailiuk, P.K. Scalable approach to fluorinated heterocycles with sulfur tetrafluoride (SF 4). J. Org. Chem., 2021, 86(17), 12181-12198.
[http://dx.doi.org/10.1021/acs.joc.1c01518] [PMID: 34424702]
[33]
Alder, C.M.; Ambler, M.; Campbell, A.J.; Champigny, A.C.; Deakin, A.M.; Harling, J.D.; Harris, C.A.; Longstaff, T.; Lynn, S.; Maxwell, A.C.; Mooney, C.J.; Scullion, C.; Singh, O.M.P.; Smith, I.E.D.; Somers, D.O.; Tame, C.J.; Wayne, G.; Wilson, C.; Woolven, J.M. Identification of a novel and selective series of itk inhibitors via a template-hopping strategy. ACS Med. Chem. Lett., 2013, 4(10), 948-952.
[http://dx.doi.org/10.1021/ml400206q] [PMID: 24900590]
[34]
Ceballos-Alcantarilla, E.; Agulló, C.; Abad-Fuentes, A.; Abad-Somovilla, A.; Mercader, J.V. Rational design of a fluopyram hapten and preparation of bioconjugates and antibodies for immunoanalysis. RSC Advances, 2015, 5(63), 51337-51341.
[http://dx.doi.org/10.1039/C5RA09124A]
[35]
Shook, B.C.; Rassnick, S.; Wallace, N.; Crooke, J.; Ault, M.; Chakravarty, D.; Barbay, J.K.; Wang, A.; Powell, M.T.; Leonard, K.; Alford, V.; Scannevin, R.H.; Carroll, K.; Lampron, L.; Westover, L.; Lim, H.K.; Russell, R.; Branum, S.; Wells, K.M.; Damon, S.; Youells, S.; Li, X.; Beauchamp, D.A.; Rhodes, K.; Jackson, P.F. Design and characterization of optimized adenosine A₂A/A₁ receptor antagonists for the treatment of Parkinson’s disease. J. Med. Chem., 2012, 55(3), 1402-1417.
[http://dx.doi.org/10.1021/jm201640m] [PMID: 22239465]
[36]
Leonard, K.; Pan, W.; Anaclerio, B.; Gushue, J.M.; Guo, Z.; DesJarlais, R.L.; Chaikin, M.A.; Lattanze, J.; Crysler, C.; Manthey, C.L.; Tomczuk, B.E.; Marugan, J.J. Non-peptidic αvβ3 antagonists containing indol-1-yl propionic acids. Bioorg. Med. Chem. Lett., 2005, 15(10), 2679-2684.
[http://dx.doi.org/10.1016/j.bmcl.2005.01.028] [PMID: 15863341]
[37]
Messina, P.A.; Mange, K.C.; Middleton, W.J. Aminosulfur trifluorides: Relative thermal stability [1]. J. Fluor. Chem., 1989, 42(1), 137-143.
[http://dx.doi.org/10.1016/S0022-1139(00)83974-3]
[38]
Lal, G.S.; Pez, G.P.; Pesaresi, R.J.; Prozonic, F.M.; Cheng, H. Bis(2-methoxyethyl)aminosulfur trifluoride: A new broad-spectrum deoxofluorinating agent with enhanced thermal stability. J. Org. Chem., 1999, 64(19), 7048-7054.
[http://dx.doi.org/10.1021/jo990566+]
[39]
Tamanini, E.; Buck, I.M.; Chessari, G.; Chiarparin, E.; Day, J.E.H.; Frederickson, M.; Griffiths-Jones, C.M.; Hearn, K.; Heightman, T.D.; Iqbal, A.; Johnson, C.N.; Lewis, E.J.; Martins, V.; Peakman, T.; Reader, M.; Rich, S.J.; Ward, G.A.; Williams, P.A.; Wilsher, N.E. Discovery of a potent nonpeptidomimetic, small-molecule antagonist of cellular inhibitor of apoptosis protein 1 (cIAP1) and X-linked inhibitor of apoptosis protein (XIAP). J. Med. Chem., 2017, 60(11), 4611-4625.
[http://dx.doi.org/10.1021/acs.jmedchem.6b01877] [PMID: 28492317]
[40]
Mitchell, M.L.; Son, J.C.; Guo, H. N1-Alkyl pyrimidinediones as non-nucleoside inhibitors of HIv-1 reverse transcriptase. Bioorganic Med. Chem. Lett., 2010, 20(5), 1589-1592.
[http://dx.doi.org/10.1016/j.bmcl.2010.01.085]
[41]
Melvin, P.R.; Ferguson, D.M.; Schimler, S.D.; Bland, D.C.; Sanford, M.S. Room temperature deoxyfluorination of benzaldehydes and α-ketoesters with sulfuryl fluoride and tetramethylammonium fluoride. Org. Lett., 2019, 21(5), 1350-1353.
[http://dx.doi.org/10.1021/acs.orglett.9b00054] [PMID: 30775926]
[42]
Danahy, K.E.; Cooper, J.C.; Van Humbeck, J.F. Benzylic fluorination of aza‐heterocycles induced by single‐electron transfer to selectfluor. Angew. Chem. Int. Ed., 2018, 57(18), 5134-5138.
[http://dx.doi.org/10.1002/anie.201801280] [PMID: 29486098]
[43]
Chausset-Boissarie, L.; Le Guen, C.; Mazzah, A.; Penhoat, M.; Melnyk, P.; Rolando, C. Direct and regioselective C(sp3)–H bond fluorination of 2-alkylazaarenes with selectfluor. Synthesis, 2021, 53(6), 1157-1162.
[http://dx.doi.org/10.1055/s-0040-1706482]
[44]
Vara, B.A.; Johnston, J.N. Enantioselective synthesis of β-fluoro amines via β-amino α-fluoro nitroalkanes and a traceless activating group strategy. J. Am. Chem. Soc., 2016, 138(42), 13794-13797.
[http://dx.doi.org/10.1021/jacs.6b07731] [PMID: 27749040]
[45]
Sadeghi, M.M.; Loghmani-Khouzani, H.; Ranjbar-Karimi, R.; Golding, B.T. Sonochemical fluorination of heterocyclic nitro compounds with Selectfluor™ (F-TEDA-BF4). Tetrahedron Lett., 2006, 47(14), 2455-2457.
[http://dx.doi.org/10.1016/j.tetlet.2006.01.037]
[46]
Rajawinslin, R.R.; Ichake, S.S.; Kavala, V.; Gawande, S.D.; Huang, Y.H.; Kuo, C.W.; Yao, C.F. Iron/acetic acid mediated synthesis of 6,7-dihydrodibenzo[b,j][1,7]phenanthroline derivatives via intramolecular reductive cyclization. RSC Advances, 2015, 5(64), 52141-52153.
[http://dx.doi.org/10.1039/C5RA06395G]
[47]
Greaney, M.F.; Al-Mkhaizim, F.Y. α-Fluorination of nitrobenzenes and nitropyridines via vicarious nucleophilic substitution of hydrogen. Synlett, 2020, 31(11), 1094-1096.
[http://dx.doi.org/10.1055/s-0039-1690862]
[48]
Kawanishi, R.; Phongphane, L.; Iwasa, S.; Shibatomi, K. Decarboxylative fluorination of 2‐pyridylacetates. Chemistry, 2019, 25(31), 7453-7456.
[http://dx.doi.org/10.1002/chem.201900565] [PMID: 31026095]
[49]
Komatsuda, M.; Suto, A.; Kondo, H., Jr; Takada, H.; Kato, K.; Saito, B.; Yamaguchi, J. Ring-opening fluorination of bicyclic azaarenes. Chem. Sci., 2022, 13(3), 665-670.
[http://dx.doi.org/10.1039/D1SC06273E] [PMID: 35173930]
[50]
Zhu, R.Y.; Tanaka, K.; Li, G.C.; He, J.; Fu, H.Y.; Li, S.H.; Yu, J.Q. Ligand-enabled stereoselective β-c(sp 3)–h fluorination: Synthesis of unnatural enantiopure anti -β-Fluoro-α-amino Acids. J. Am. Chem. Soc., 2015, 137(22), 7067-7070.
[http://dx.doi.org/10.1021/jacs.5b04088] [PMID: 26001406]
[51]
Ishihara, K.; Nishimura, K.; Yamakawa, K. Enantio‐ and site‐selective α‐fluorination of N ‐Acyl 3,5‐Dimethylpyrazoles catalyzed by Chiral π–Cu II complexes. Angew. Chem. Int. Ed., 2020, 59(40), 17641-17647.
[http://dx.doi.org/10.1002/anie.202007403] [PMID: 32633892]
[52]
Park, H.; Verma, P.; Hong, K.; Yu, J.Q. Controlling Pd(iv) reductive elimination pathways enables Pd(ii)-catalysed enantioselective C(sp3)−H fluorination. Nat. Chem., 2018, 10(7), 755-762.
[http://dx.doi.org/10.1038/s41557-018-0048-1] [PMID: 29892027]
[53]
Ying, W.; DesMarteau, D.D.; Gotoh, Y. N-fluoro-bis[(trifluoromethyl)sulfonyl]imide: Electrophilic fluorination of imines and some methyl-substituted pyridines. Tetrahedron, 1996, 52(1), 15-22.
[http://dx.doi.org/10.1016/0040-4020(95)00884-B]
[54]
Frohn, M.; Liu, L.; Siegmund, A.C.; Qian, W.; Amegadzie, A.; Chen, N.; Tan, H.; Hickman, D.; Wood, S.; Wen, P.H.; Bartberger, M.D.; Whittington, D.A.; Allen, J.R.; Bourbeau, M.P. The development of a structurally distinct series of BACE1 inhibitors via the (Z)-fluoro-olefin amide bioisosteric replacement. Bioorg. Med. Chem. Lett., 2020, 30(14), 127240.
[http://dx.doi.org/10.1016/j.bmcl.2020.127240] [PMID: 32527542]
[55]
Caplan, N.A.; Pogson, C.I.; Hayes, D.J.; Blackburn, G.M. The synthesis of novel bisphosphonates as inhibitors of phosphoglycerate kinase (3-PGK). J. Chem. Soc., Perkin Trans. 1, 2000, (3), 421-437.
[http://dx.doi.org/10.1039/a906507e]
[56]
He, Z.T.; Jiang, X.; Hartwig, J.F. Stereodivergent construction of tertiary fluorides in vicinal stereogenic pairs by allylic substitution with iridium and copper catalysts. J. Am. Chem. Soc., 2019, 141(33), 13066-13073.
[http://dx.doi.org/10.1021/jacs.9b04440] [PMID: 31343170]
[57]
Yang, S.Q.; Wang, Y.F.; Zhao, W.C.; Lin, G.Q.; He, Z.T. Stereodivergent synthesis of tertiary fluoride-tethered allenes via copper and palladium dual catalysis. J. Am. Chem. Soc., 2021, 143(19), 7285-7291.
[http://dx.doi.org/10.1021/jacs.1c03157] [PMID: 33970628]
[58]
Das, A.; Joshi, H.; Singh, V.K. Asymmetric α-functionalization of 2-alkyl azaarenes: Synthesis of tertiary fluorides having vicinal stereogenic centers. Org. Lett., 2021, 23(24), 9441-9445.
[http://dx.doi.org/10.1021/acs.orglett.1c03626] [PMID: 34870439]
[59]
Bräse, S.; Allendörfer, N.; Es-Sayed, M.; Nieger, M. Novel aromatic fluoroolefins via fluoro-julia-kocienski olefination. Synthesis, 2010, 2010(20), 3439-3448.
[http://dx.doi.org/10.1055/s-0030-1258198]
[60]
Shen, S.; He, X.; Yang, Z.; Zhang, L.; Liu, Y.; Zhang, Z.; Wang, W.; Liu, W.; Li, Y.; Huang, D.; Sun, K.; Ni, X.; Yang, X.; Chu, X.; Cui, Y.; Lv, Q.; Lan, J.; Zhou, F. Discovery of an orally bioavailable dual pi3k/mtor inhibitor based on sulfonyl-substituted morpholinopyrimidines. ACS Med. Chem. Lett., 2018, 9(7), 719-724.
[http://dx.doi.org/10.1021/acsmedchemlett.8b00167] [PMID: 30034607]
[61]
Samorì, C.; Guerrini, A.; Varchi, G.; Fontana, G.; Bombardelli, E.; Tinelli, S.; Beretta, G.L.; Basili, S.; Moro, S.; Zunino, F.; Battaglia, A. Semisynthesis, biological activity, and molecular modeling studies of C-ring-modified camptothecins. J. Med. Chem., 2009, 52(4), 1029-1039.
[http://dx.doi.org/10.1021/jm801153y] [PMID: 19530720]
[62]
Chen, J.; Sambaiah, T.; Illarionov, B.; Fischer, M.; Bacher, A.; Cushman, M. Design, synthesis, and evaluation of acyclic C-nucleoside and N-methylated derivatives of the ribitylaminopyrimidine substrate of lumazine synthase as potential enzyme inhibitors and mechanistic probes. J. Org. Chem., 2004, 69(21), 6996-7003.
[http://dx.doi.org/10.1021/jo048975f] [PMID: 15471444]
[63]
Liu, X.J.; Jin, S.; Zhang, W.Y.; Liu, Q.Q.; Zheng, C.; You, S.L. Sequence‐dependent stereodivergent allylic alkylation/fluorination of acyclic ketones. Angew. Chem. Int. Ed., 2020, 59(5), 2039-2043.
[http://dx.doi.org/10.1002/anie.201912882] [PMID: 31693789]
[64]
Meanwell, M.; Nodwell, M.B.; Martin, R.E.; Britton, R. A convenient late-stage fluorination of pyridylic C−H bonds with N -fluorobenzenesulfonimide. Angew. Chem. Int. Ed., 2016, 55(42), 13244-13248.
[http://dx.doi.org/10.1002/anie.201606323] [PMID: 27653634]
[65]
Meanwell, M.; Adluri, B.S.; Yuan, Z.; Newton, J.; Prevost, P.; Nodwell, M.B.; Friesen, C.M.; Schaffer, P.; Martin, R.E.; Britton, R. Direct heterobenzylic fluorination, difluorination and trifluoromethylthiolation with dibenzenesulfonamide derivatives. Chem. Sci., 2018, 9(25), 5608-5613.
[http://dx.doi.org/10.1039/C8SC01221K] [PMID: 30061993]
[66]
Kiselyov, A.S.; Strekowski, L. A reaction of n-fluoropyridinium cation with diazocarbonyl compounds. Heterocycles, 1994, 38(2), 259-262.
[http://dx.doi.org/10.3987/COM-93-6582]
[67]
Kiselyov, A.S. Reaction of N-fluoropyridinium fluoride with isonitriles and diazo compounds: A one-pot synthesis of (pyridin-2-yl)-1H-1,2,3-triazoles. Tetrahedron Lett., 2006, 47(15), 2631-2634.
[http://dx.doi.org/10.1016/j.tetlet.2006.02.030]
[68]
Kiefl, G.M.; Gulder, T. α-Functionalization of Ketones via a Nitrogen Directed Oxidative Umpolung. J. Am. Chem. Soc., 2020, 142(49), 20577-20582.
[http://dx.doi.org/10.1021/jacs.0c10700] [PMID: 33231441]
[69]
Huang, X.; Liu, W.; Ren, H.; Neelamegam, R.; Hooker, J.M.; Groves, J.T. Late stage benzylic C-H fluorination with [¹⁸F]fluoride for PET imaging. J. Am. Chem. Soc., 2014, 136(19), 6842-6845.
[http://dx.doi.org/10.1021/ja5039819] [PMID: 24766544]
[70]
Chambers, R.D.; Holling, D.; Sandford, G.; Batsanov, A.S.; Howard, J.A.K. Elemental fluorine. J. Fluor. Chem., 2004, 125(5), 661-671.
[http://dx.doi.org/10.1016/j.jfluchem.2003.11.012]
[71]
Munoz, S.B.; Krishnamurti, V.; Barrio, P.; Mathew, T.; Prakash, G.K.S. Direct difluorination–hydroxylation, trifluorination, and C(sp 2)–H fluorination of enamides. Org. Lett., 2018, 20(4), 1042-1045.
[http://dx.doi.org/10.1021/acs.orglett.7b03994] [PMID: 29384686]
[72]
Burgey, C.S.; Robinson, K.A.; Lyle, T.A.; Sanderson, P.E.J.; Lewis, S.D.; Lucas, B.J.; Krueger, J.A.; Singh, R.; Miller-Stein, C.; White, R.B.; Wong, B.; Lyle, E.A.; Williams, P.D.; Coburn, C.A.; Dorsey, B.D.; Barrow, J.C.; Stranieri, M.T.; Holahan, M.A.; Sitko, G.R.; Cook, J.J.; McMasters, D.R.; McDonough, C.M.; Sanders, W.M.; Wallace, A.A.; Clayton, F.C.; Bohn, D.; Leonard, Y.M.; Detwiler, T.J., Jr; Lynch, J.J., Jr; Yan, Y.; Chen, Z.; Kuo, L.; Gardell, S.J.; Shafer, J.A.; Vacca, J.P. Metabolism-directed optimization of 3-aminopyrazinone acetamide thrombin inhibitors. Development of an orally bioavailable series containing P1 and P3 pyridines. J. Med. Chem., 2003, 46(4), 461-473.
[http://dx.doi.org/10.1021/jm020311f] [PMID: 12570369]
[73]
Hall, A.; Billinton, A.; Brown, S.H.; Clayton, N.M.; Chowdhury, A.; Giblin, G.M.P.; Goldsmith, P.; Hayhow, T.G.; Hurst, D.N.; Kilford, I.R.; Naylor, A.; Passingham, B.; Winyard, L. Non-acidic pyrazole EP1 receptor antagonists with in vivo analgesic efficacy. Bioorg. Med. Chem. Lett., 2008, 18(11), 3392-3399.
[http://dx.doi.org/10.1016/j.bmcl.2008.04.018] [PMID: 18462938]
[74]
Luise, N.; Wyatt, P.G. Diversity-oriented synthesis of bicyclic fragments containing privileged azines. Bioorg. Med. Chem. Lett., 2019, 29(2), 248-251.
[http://dx.doi.org/10.1016/j.bmcl.2018.11.046] [PMID: 30501964]
[75]
Shavrina, O.M.; Bezdudny, A.V.; Rassukana, Y.V. Synthesis and some transformations of all three isomers of α,α-difluoropyridinylacetonitrile. J. Fluor. Chem., 2021, 246, 109792.
[http://dx.doi.org/10.1016/j.jfluchem.2021.109792]
[76]
Shavrina, O.M.; Onys’ko, P.P.; Rassukana, Y.V. [Difluoro(pyridinyl)methyl]phosphonates. Chem. Heterocycl. Compd., 2023, 59(6-7), 415-419.
[http://dx.doi.org/10.1007/s10593-023-03210-1]
[77]
Shavrina, O.; Bezgubenko, L.; Bezdudny, A.; Onys’ko, P.; Rassukana, Y. α-(Imino)pyridyldifluoroethyl phosphonates: Novel promising building blocks in synthesis of biorelevant aminophosphonic acids derivatives. Organics, 2021, 2(2), 72-83.
[http://dx.doi.org/10.3390/org2020007]
[78]
Taylor, S.D.; Mirzaei, F.; Sharifi, A.; Bearne, S.L. Synthesis of methylene- and difluoromethylenephosphonate analogues of uridine-4-phosphate and 3-deazauridine-4-phosphate. J. Org. Chem., 2006, 71(25), 9420-9430.
[http://dx.doi.org/10.1021/jo0617666] [PMID: 17137369]
[79]
Shavrina, O.M.; Onys’ko, P.P.; Rassukana, Y.V. Mono- and difluorination of methylene group in isomeric pyrimidinyl- and pyridinylacetates with N-fluorobenzenesulfonimide. J. Fluor. Chem., 2022, 261-262, 110027.
[http://dx.doi.org/10.1016/j.jfluchem.2022.110027]
[80]
Chupakhin, O.N.; Charushin, V.N.; van der Plas, H.C. Nucleophilic substitution of hydrogen in azines. Tetrahedron, 1988, 44(1), 1-34.
[http://dx.doi.org/10.1016/S0040-4020(01)85088-2]

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