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Fluorinated Indolizines

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Fluorine in Heterocyclic Chemistry Volume 1

Abstract

The chapter is devoted to the synthesis and application of indolizines bearing fluorine atoms, perfluorinated alkyl (aryl) groups, and COCF3 fragments.

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References

  1. (a) Flitsch W (1984) Pyrroles with fused six-membered heterocyclic rings: a-fused. . In: Katritzky A, Rees CW (ed) Comprehensive heterocyclic chemistry 4:443–496. (b) Swinborne P-J, Hunt JH, Klinkert G. (1978) Advances in indolizine chemistry. Adv Heteroc Chem 23:103–167. (c) Prostakov NS, Baktibaev OB (1975) Usp Khim 9:1649–1687. (d) Mosby WL (1961) Heterocyclic systems with bridgehead nitrogen atom, Part I. Interscience, New York, pp 239–371. (e) Borrows ET, Holland DO (1948) The chemistry of pyrrocolines and of the octahydropyrrocolines. Chem Rev 42:611–643. (f) Kost AN, Sagitullin RS, Gromov SP (1977) Nucleophilic amination and recyclization of the indolizine nucleus. Heterocycles 7:997–1001

    Google Scholar 

  2. Kobylianskii IJ, Novikov MS, Khlebnikov AF (2011) Formation and reactivity of gem-difluoro-substituted pyridinium ylides: experimental and DFT investigation. J Fluor Chem 3:175–180

    Article  Google Scholar 

  3. Banks RE, Mohialdin SN (1988) Synthesis of indolizines from N-(2,2,2-trifluoroethyl)-pyridinium triflate; evidence for the generation of pyridinium (trifluoromethyl)methylide. J Fluor Chem 38:289–294

    Article  CAS  Google Scholar 

  4. Banks RE, Mohialdin SN (1986) Synthesis of indolizines from pyridinium (trifluoroacetyl)methylide and fluorinated dipolarophiles. J Fluor Chem 34:275–280

    Article  CAS  Google Scholar 

  5. Lungu NC, Depret A, Delattre F, Surpateanu GG, Cazier F, Woisel P, Shirali P, Surpateanu G (2005) Synthesis of a new fluorinated fluorescent β-cyclodextrin sensor. J Fluor Chem 3:385–388

    Article  Google Scholar 

  6. Kobayashi Y, Kumadaki I, Fujino S (1977) 1,3-Dipolar cycloaddition reaction of aromatic N-oxide with hexafluorobutyne. Heterocycles 2:871–876

    Article  Google Scholar 

  7. Shinji Y, Emiko O (2008) An unusual reaction of a pyridinium ylide with 1,1-dicyanoethylene derivatives. Chem Lett 6:628–629

    Google Scholar 

  8. Babaev EV (1987) Synthesis, structure and ambiphilic reactivity of nitroindolizines. PhD thesis, Moscow University, Moscow, 182 pp

    Google Scholar 

  9. (a) Bobrovskii SI, Babaev EV, Bundel YuG (1987) Recyclization of 3-acyl-6(8)-nitroindolizines to 2-acyl(carboxy)-5(7)- nitroindoles. Zh Org Khim (Russ) 10:2240–2241. (b) Babaev EV, Bobrovskii SI, Bundel YuG (1988) Recyclization of 2-phenyl-6(8)-nitro-3-trifluoracetyl-indolizine forming 3-phenyl-5(7)-nitroindole-2-carboxylic acid. Chem Heteroc Comp 11:1307. (c) Terenin VI, Babaev EV, Yurovskaya MA, Bundel YuG (1992) New recyclizations and transformations of azines. Chem Heteroc Comp 6:658–670

    Google Scholar 

  10. Kuznetsov AG, Bush AA, Babaev EV (2007) Synthesis and reactivity of 5-Br(I)-indolizines and their parallel cross-coupling reactions. Tetrahedron 4:749–756

    Google Scholar 

  11. American Home Products Corporation (1998) Saturated and unsaturated pyridazino[4,5-B] indolizines useful as antidementia agents. US Patent 5,756,501

    Google Scholar 

  12. Krivoshein AE, Krivorotov DV, Vorob’ev MV, Petrov ML, Polukeev VA (2007) Reaction of perfluorocarboxylic anhydrides with 2-(4-chlorophenyl)-1-(3,4-dimethoxyphenyl)-8,9-dimethoxypyrrolo[2,1-a]isoquinoline. Russ J Gen Chem 2:319–320

    Article  Google Scholar 

  13. Terenin VI, Ivanov AS (2007) Effect of the trifluoroacetyl group on the direction of the recyclization of the pyrazine ring in 6-trifluoroacetylpyrrolo[1,2-a]pyrazinium salts. Chem Heterocyc Comp 11:1460–1465

    Article  Google Scholar 

  14. Bobrovskii SI, Lushnikov DE, Bundel’ YuG (1989) De-acylation, re-acylation and isomerization of 2-methyl-3-trihalogenacetyl indolizines. Zh Org Khim 10:2251–2252 (Russ)

    Google Scholar 

  15. Ohta T, Fukuda T, Ishibashi F, Iwao M (2009) Design and synthesis of lamellarin D analogues targeting topoisomerase I. J Org Chem 21:8143–8153

    Article  Google Scholar 

  16. Mirek J, Haas A (1982) The reaction of indolizines and acetylindolizines with trifluoromethylsulfenyl chloride. J Fluor Chem 19:67–70

    Article  Google Scholar 

  17. Do H-D, Daugulis O (2011) A general method for copper-catalyzed arene cross-dimerization. J Am Chem Soc 34:13577–13586

    Article  Google Scholar 

  18. Bobrovskii SI, Lushnikov DE, Bundel’ YG (1989) Structure and ambiphilic reactivities of indolizines. 5. Acylation of 2-methylindolizine. Chem Heterocycl Comp 12:1360–1364

    Article  Google Scholar 

  19. Shen Y, Zhang Y, Jiang G-F (2002) A convenient synthesis of perfluoroalkylated indolizinylphosphonates. Synthesis 6:714–716

    Article  Google Scholar 

  20. Shen Y, Zhang Y, Sun J (2002) Regiospecific synthesis of perfluoroalkylated pyrrolo[2,1-a]isoquinolinyl phosphonates. J Fluor Chem 2:157–162

    Article  Google Scholar 

  21. Zhang X-C, Huang W-Y (1999) A one-step approach to 1-(fluoroalkyl)indolizine derivatives. Synthesis 1:51–54

    Article  Google Scholar 

  22. Banks RE, Khaffaff SN (1991) Fluorocarbon derivatives of nitrogen. Part 18. Synthesis of fluorinated indolizines through reactions of pyridinium ethoxycarbonylmethylide or pyridinium phenacylide with perfluoropropene, perfluorobut-2-yne and 3,3,3-trifluoro-propyne. J Fluor Chem 3:407–418

    Article  Google Scholar 

  23. Zhu S-Z, Qin C-Y, Wang Y-L, Chu Q-L (1999) Preparation of 1-trifluoroacetyl indolizines and their derivatives via the cycloaddition of pyridinium N-ylides with 4-ethoxy-1,1,1-trifluorobut-3-en-2-one. J Fluor Chem 2:183–188

    Article  Google Scholar 

  24. Fang X, Wu Y-M, Deng J, Wang S-W (2004) Synthesis of monofluorinated indolizines and their derivatives by the 1,3-dipolar reaction of N-ylides with fluorinated vinyl tosylates. Tetrahedron 25:5487–5494

    Article  Google Scholar 

  25. Shimizu K, Iizuka M, Kissei Pharmaceutical Co Ltd (2012) Patent US2012/15972

    Google Scholar 

  26. Wu K, Chen Q-Y (2003) A facile synthetic method for 2-fluoroindolizines from 1-chloro-2,2,2-trifluoroethane (HCFC-133a) and 1,1,1,2-tetrafluoroethane (HFC-134a). J Fluor Chem 2:171–174

    Article  Google Scholar 

  27. Zhang X-C, Huang W-Y (1998) Cycloaddition reactions of N-(cyanomethyl)pyridinium ylides with 2,2-dihydropolyfluoroalkanoates. J Fluor Chem 1:13–16

    Article  CAS  Google Scholar 

  28. Zhang X-C, Huang W-Y (1998) A convenient synthesis of polyfluoroalkyl-substituted pyrazolo[1,5-a]pyridine, pyrrolo[1,2-b]pyridazine and indolizine derivatives. J Fluor Chem 1:57–64

    Article  Google Scholar 

  29. Peng W, Zhu S (2001) Reactions of N-benzyl-pyridinium or -isoquinolinium ylides with ethyl 3-fluoro-3-(fluoroalkyl)acrylates to give fluoroalkylsubstituted indolizine and pyrrolo[2,1-a]isoquinoline derivatives. J Chem Soc Perkin Trans 1 23:3204–3210

    Google Scholar 

  30. Wu K, Chen Q-Y (2003) Synthesis of fluorinated indolizines and 4H-pyrrolo[1,2-a]benzimidazoles via 1,3-dipolar cycloaddition of fluoroalkenes to N-ylides. Synthesis 1:35–40

    CAS  Google Scholar 

  31. Banks RE, Hitchen SM, Thomson J (1982) Reactions of pyridinium t-butoxycarbonyl-methylide with perfluoropropene and some fluoroaromatics. J Fluor Chem 20:127–132

    Article  CAS  Google Scholar 

  32. Banks RE, Thomson J (1985) Reaction of pyridinium t-butoxycarbonylmethylide with perfluoropropene and with some fluoroaromatic compounds: synthesis of some fluorinated indolizines. J Chem Res Miniprint 2:671–689

    Google Scholar 

  33. Matsumoto K, Ikemi Y, Konishi H, Shi X-L, Uchida T (1988) Site selectivity in the 1,3-dipolar cycloaddition reaction of unsymmetric pyridinium bis(methoxycarbonyl)methylides with methyl propiolate. Heterocycles 11:2557–2562

    Article  Google Scholar 

  34. Barluenga J, Lonzi G, Riesgo L, Lopez LA, Tomas M (2010) Pyridine activation via copper(I)-catalyzed annulation toward indolizines. J Am Chem Soc 38:13200–13202

    Article  Google Scholar 

  35. Tsuge O, Kanemasa S, Kuraoka S, Takenaka Shigeori (1984) N-(Trimethylsilylmethyl)-pyridinium trifluoromethanesulfonates as facile precursors for nonstabilized pyridinium methylides. Chem Lett 13:279–280

    Google Scholar 

  36. Hynd G, Argenta Discovery Limited (2008) CRTH2 antagonists. Patent WO2008/74966

    Google Scholar 

  37. Hynd G, Ray NC, Finch H, Middlemiss D, Cramp MC, Blaney PM, Williams K, Griffon Y, Harrison TK, Crackett P (2009) Indolizine derivatives. Patent US2009/163534

    Google Scholar 

  38. Kel’in AV, Sromek AW, Gevorgyan V (2001) A novel Cu-assisted cycloisomerization of alkynyl imines: efficient synthesis of pyrroles and pyrrole-containing heterocycles. J Am Chem Soc 9:2074–2075

    Article  Google Scholar 

  39. Rogness DC, Markina NA, Waldo JP, Larock RC (2012) Synthesis of pyrido[1,2-a]indole malonates and amines through aryne annulation. J Org Chem 6:2743–2755

    Article  Google Scholar 

  40. Kiselyov AS (2006) A convenient procedure for the synthesis of fused fluoro isoquinolines. Tetrahedron 4:543–548

    Article  Google Scholar 

  41. Shen D-Q, Wu N, Li Y-P, Wu Z-P, Huang Z-S, Gu L-Q, An L-K, Zhang H-B (2010) Design, synthesis, and cytotoxicity of indolizinoquinoxaline-5,12-dione derivatives, novel DNA topoisomerase IB inhibitors. Austr J Chem 7:1116–1121

    Article  Google Scholar 

  42. Shen D-Q, Wu Z-P, Wu X-W, An Z-Y, Bu X-Z, Gu L-Q, Huang Z-S, An L-K (2010) Synthesis and antiproliferative activity of indolizinophthalazine-5,12-dione derivatives, DNA topoisomerase IB inhibitors. Eur J Med Chem 9:3938–3942

    Article  Google Scholar 

  43. Cheng Y, An L-K, Wu N, Wang X-D, Bu X-Z, Huang Z-S, Gu L-Q (2008) Synthesis, cytotoxic activities and structure–activity relationships of topoisomerase I inhibitors: indolizinoquinoline-5,12-dione derivatives. Bioorg Med Chem 8:4617–4625

    Article  Google Scholar 

  44. Ye S, Wu J, Liu J (2012) Generation of 4-polyfluoroaryl pyrrolo[1,2-a]quinolines via C-H bond activation. Chem Comm 41:5028–5030

    Article  Google Scholar 

  45. Synta Pharmaceuticals Corp (2004) Synthesis of indolizines. Patent WO2004/24727

    Google Scholar 

  46. Hund G, Argenta Discovery Ltd (2007) Indolizine derivatives as ligands of the CRTH2 receptor. Patent WO2007/31747

    Google Scholar 

  47. Chai DI, Lautens M (2009) Tandem Pd-catalyzed double C-C bond formation: effect of water. J Org Chem 8:3054–3061

    Article  Google Scholar 

  48. Bedjeguelal K, Bienayme H, Dumoulin A, Poigny S, Schmitt P, Tam E (2006) Discovery of protein-protein binding disruptors using multi-component condensations small molecules. Bioorg Med Chem Lett 15:3998–4001

    Article  Google Scholar 

  49. Sun L-L, Liao Z-Y, Tang R-Y, Deng C-L, Zhang X-G (2012) Palladium and copper cocatalyzed tandem N-H/C-H bond functionalization: synthesis of CF3-containing indolo- and pyrrolo[2,1-a]isoquinolines. J Org Chem 6:2850–2856

    Article  Google Scholar 

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Acknowledgments

This work was funded by RFBR (grant 12-03-00644-a).

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Authors and Affiliations

  1. Department of Chemistry, Moscow State University, Leninskie Gory, Moscow, 119992, Russian Federation

    Eugene V. Babaev

  2. Moscow Institute of Physics and Technology, Institutskii per. 9, 141700, Dolgoprudny, Moscow Region, Russia

    Eugene V. Babaev

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  1. Eugene V. Babaev
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Correspondence to Eugene V. Babaev .

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Editors and Affiliations

  1. Department of Chemistry, Moscow State University, Moscow, Russia

    Valentine Nenajdenko

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Babaev, E.V. (2014). Fluorinated Indolizines. In: Nenajdenko, V. (eds) Fluorine in Heterocyclic Chemistry Volume 1. Springer, Cham. https://doi.org/10.1007/978-3-319-04346-3_4

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