Living Edition
| Editors: Jinbo Hu, Teruo Umemoto

BF3 Fluorination for Preparing Alkyl Fluorides

  • Chang-Hua DingEmail author
  • Xue-Long HouEmail author
Living reference work entry
DOI: https://doi.org/10.1007/978-981-10-1855-8_43-1


Monofluorination is an important access to introduce fluorine atom into organic molecules, which is realized by the strategies employing diethylaminosulfur trifluoride (DAST), tris(diethylamino)sulfonium difluorotrimethylsilicate (TAS-F), hydrogen fluoride, etc. as reagents as shown in other entries of the book. BF3.OEt2 as an ubiquitous reagent is usually used as a Lewis acid in synthetic organic transformations. However, BF3·OEt2 may also serve as an effective nucleophilic fluoride source in the fluorination reaction owing to the property of boron to form ate complex with some Lewis bases and anions. The mechanism of BF3 for fluoride transfer possibly involves a migration of the fluoride via an ate complex readily generated, trifluoroborate with the form of BF3X (X = Lewis base). Because of its high fluoride content and easy handling in the reaction, the use of BF3·OEt2as a fluorine source has attracted great attention of synthetic chemists. A comprehensive review has...

This is a preview of subscription content, log in to check access.


  1. 1.
    Cresswell AJ; Davies SG, Roberts PM, Thomson JE (2015) Beyond the Balz−Schiemann Reaction: The Utility of Tetrafluoroborates and Boron Trifluoride as Nucleophilic Fluoride Sources. Chem Rev 115: 566−611.CrossRefPubMedGoogle Scholar
  2. 2.
    Jaber JJ, Mitsui K, Rychnovsky SD (2001) Stereoselectivity and regioselectivity in the segment-coupling Prins cyclization. J Org Chem 66: 4679–4686.CrossRefPubMedGoogle Scholar
  3. 3.
    Al-Mutairi EH, Crosby SR, Darzi J, Harding JR, Hughes RA, King CD, Simpson TJ, Smith RW, Willis CL (2001) Stereocontrolled synthesis of 2,4,5-trisubstituted tetrahydropyrans. Chem Commun 835-836.Google Scholar
  4. 4.
    Kataoka K, Ode Y, Matsumoto M, Nokami J (2006) Convenient synthesis of highly optically active 2,3,4,6-tetrasubstituted tetrahydropyrans via Prins cyclization reaction (PCR) of optically active homoallylic alcohols with aldehydes. Tetrahedron 62: 2471−2483.CrossRefGoogle Scholar
  5. 5.
    Launay GG, Slawin AMZ, O’Hagan D (2010) Prins fluorination cyclisations: preparation of 4-fluoro-pyran and -piperidine heterocycles. Beilstein J Org Chem 6: 41.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Wölfling J, Frank É, Schneider G, Tietze LF (1998) Synthesis of azasteroids and D-homosteroids by intramolecular cyclization reactions of steroid arylimines. Synlett 1205−1206.CrossRefGoogle Scholar
  7. 7.
    Wölfling J, Frank É, Schneider G, Tietze LF (1999) Synthesis of novel steroid alkaloids by cyclization of arylimines from estrone. Eur J Org Chem 3013–3020.CrossRefGoogle Scholar
  8. 8.
    Berge J, Claridge S, Mann A, Muller C, Tyrrell E (1997) A diastereoselective synthesis of benzopyrans using a novel intramolecular Nicholas reaction in the key cyclisation step. Tetrahedron Lett 38: 685–686.CrossRefGoogle Scholar
  9. 9.
    Mann AL, Muller C, Tyrrell E (1998) A diastereoselective cobalt-mediated synthesis of benzopyrans using a novel variation of an intramolecular Nicholas reaction in the key cyclisation step: optimisation and biological evaluation. J Chem Soc Perkin Trans 1 1427–1438.CrossRefGoogle Scholar
  10. 10.
    Tyrrell E, Millet J, Tesfa KH, Williams N, Mann A, Tillett C, Muller C (2007) A study into asymmetric Nicholas cyclisation reactions. Tetrahedron 63: 12769−12778.CrossRefGoogle Scholar
  11. 11.
    Olier C, Gastaldi S, Christie SDR, Bertrand MP (2007) Unprecedented cyclization of Nicholas cations onto unactivated terminal alkenes: tandem trapping of cationic intermediates. Synlett 423−426.Google Scholar
  12. 12.
    Patel MM, Green JR (1999) [4+3] and fluorinative [4+3] cycloadditions of alkyne 1,4-diether dicobalt complexes. Chem Commun 509−510.Google Scholar
  13. 13.
    Lu Y, Green JR (2001) Tandem 4+3 cycloaddition/nucleophilic trapping reactions of butyne-1,4-diether dicobalt hexacarbonyl complexes. Synlett 243−247.CrossRefGoogle Scholar
  14. 14.
    Cui J, Jia Q, Feng RZ, Liu SS, He T, Zhang C (2014) Boron trifluoride etherate functioning as a fluorine source in an iodosobenzene-mediated intramolecular aminofluorination of homoallylic amines. Org Lett 16: 1442−1445.CrossRefPubMedGoogle Scholar
  15. 15.
    Liu GQ, Li YM (2014) Regioselective (diacetoxyiodo)benzene-promoted halocyclization of unfunctionalized olefins. J Or. Chem 79: 10094−10109.CrossRefGoogle Scholar
  16. 16.
    Henbest HB, Wrigley TI (1957) Aspects of stereochemistry. Part IX. The formation of fluorohydrins from the cholesterol 5,6-epoxides and boron trifluoride–ether complex. J Chem Soc 4765−4768.Google Scholar
  17. 17.
    Bowers A, Ringold HJ (1963) Process for the production of 6-fluoro steroids. U.S. Patent 3115492.Google Scholar
  18. 18.
    Bowers A, CuÉllar Ibáñez L, Ringold HJ (1959) Steroids—CXX synthesis of halogenated steroid hormones: new routes to 6α-fluorotestosterone and the 6α- and 6β-fluoro analogs of progesterone. The synthesis of 6α- and 6β-fluoro reichstein’s compound “S” and 6α- and 6β-fluorodesoxycorticosterone acetate. Tetrahedron 7: 138−152.CrossRefGoogle Scholar
  19. 19.
    Fürst A, Plattner PA (1949) Über steroide und sexualhormone. 160. Mitteilung. 2α,3α- und 2β,3β-Oxido-chlolestane; konfiguration der 2-oxy-cholestane. Helv Chim Acta 32: 275−283.CrossRefPubMedGoogle Scholar
  20. 20.
    Blackett BN, Coxon JM, Hartshorn MP, Richards KE (1969) Reactions of epoxides—XXIV: the BF3-catalysed rearrangement of 4,5- and 5,6-epoxycholestanes. Tetrahedron 25: 4999−5005.CrossRefGoogle Scholar
  21. 21.
    Blunt JW, Hartshorn MP, Kirk DN (1965) Reactions of epoxides—V: rearrangements of 5,6-epoxy-6-methyl-cholestanes with boron trifluoride. Tetrahedron 21: 559−567.CrossRefGoogle Scholar
  22. 22.
    Guest IG, Marples BA (1970) Steroids. Part X. Boron trifluoride-catalysed rearrangements of 5,6-epoxy-3β-hydroxy- and 5,6-epoxy-3β-methoxy-steroids. J Chem Soc C 1626−1629.CrossRefGoogle Scholar
  23. 23.
    St Enev V, Tsankova ET (1991) Lewis acid catalysed rearrangement of 7,11-epoxyisogermacrone. Formation of a new carbon skeleton. Tetrahedron 47: 6399−6406.CrossRefGoogle Scholar
  24. 24.
    Coxon JM, Hartshorn MP, Lewis AJ, Richards KE, Swallow WH (1969) Some rearrangements of substituted ethylene oxides. Tetrahedron 25: 4445−4448.CrossRefGoogle Scholar
  25. 25.
    Coxon JM, Hartshorn MP, Swallow WH (1974) Acetate participation in acyclic epoxide systems. acid-catalyzed rearrangements of trans- and cis-1-acetoxy-3,4-epoxypentanes, -4,5-epoxyhexanes, and -5,6-epoxyheptanes. J Org Chem 39: 1142−1148.CrossRefGoogle Scholar
  26. 26.
    Ashwell M, Jackson RFW, Kirk JM (1990) Preparation of α-substituted S-phenylthio esters from 2-nitro-2-phenylthio oxiranes. Tetrahedron 46: 7429−7442.CrossRefGoogle Scholar
  27. 27.
    House HO (1956) The rearrangement of α,β-epoxy ketones. III. The intramolecular nature of the rearrangement. J Am Chem Soc 78: 2298−2302.CrossRefGoogle Scholar
  28. 28.
    House HO, Ryerson GD (1961) The rearrangement of α,β-epoxy ketones. VIII. Effect of substituents on the rate of rearrangement J Am Chem Soc 83: 979−983.CrossRefGoogle Scholar
  29. 29.
    Weber FG, Giese H, Koeppel H, Reinhold M, Strobel R, Radeglia R, Storek W (1985) Substituenteneffekte in den 13C-NMR-spektren von diastereomeren chalkondihalogeniden. V. synthese, stereochemie und spektroskopie von chalkonfluorhydrinen. J Prakt Chem 327: 133−143.CrossRefGoogle Scholar
  30. 30.
    Cresswell AJ, Davies SG, Lee JA, Roberts PM, Russell AJ, Thomson JE, Tyte MJ (2010) β-Fluoroamphetamines via the stereoselective synthesis of benzylic fluorides. Org Lett 12: 2936−2939.CrossRefPubMedGoogle Scholar
  31. 31.
    Islas-González G, Puigjaner C, Vidal-Ferran A, Moyano A, Riera A, Pericàs MA (2004) Boron trifluoride-induced reactions of phenylglycidyl ethers: a convenient synthesis of enantiopure, stereodefined fluorohydrins. Tetrahedron Lett 45: 6337−6341.CrossRefGoogle Scholar
  32. 32.
    Giannini G (1996) The use of BF3·OEt2 in the synthesis of fluorinated anthracyclinones. Gazz Chim Ital 126: 771-772.Google Scholar
  33. 33.
    Lombardi P, Animati F, Cipollone A, Giannini G, Monteagudo E Arcamone F (1995) Synthesis and conformational preference of novel 8-fluoroanthracyclines. Acta Biochim Pol 42: 433−444.PubMedGoogle Scholar
  34. 34.
    Voronkov MG, Fedotova LA (1967) Heteroatom derivatives of aziridine. IV. Reaction of ethylenimine with boron trifluoride. Chem Heterocycl Compd 2: 408−412.CrossRefGoogle Scholar
  35. 35.
    Sugihara Y, Iimura S, Nakayama J (2002) Aza-pinacol rearrangement: acid-catalyzed rearrangement of aziridines to imines. Chem Commun 134−135.Google Scholar
  36. 36.
    Legters J, Willems JGH, Thijs L, Zwanenburg B (1992) Synthesis of functionalized amino acids by ring-opening reactions of aliphatically substituted aziridine-2-carboxylic esters. Recl Trav Chim Pays-Bas 111: 59−68.CrossRefGoogle Scholar
  37. 37.
    Reddy R, Jaquith JB, Neelagiri VR, Saleh-Hanna S, Durst T (2002) Asymmetric synthesis of the highly methylated tryptophan portion of the hemiasterlin tripeptides. Org Lett 4: 695−697.CrossRefPubMedGoogle Scholar
  38. 38.
    Hu XE (2002) Lewis acid promoted regio- and stereoselective hetero nucleophilic addition to a piperidinyl aziridine. synthesis of trans 3-amino-4-substituted piperidines. Tetrahedron Lett 43: 5315−5318.CrossRefGoogle Scholar
  39. 39.
    Ding CH, Dai LX, Hou XL (2004) An efficient and highly regioselective fluorination of aziridines using BF3·OEt2 as fluorine source. Synlett: 2218−2220.Google Scholar
  40. 40.
    Pasceri R, Bartrum HE, Hayes CJ, Moody CJ (2012) Nucleophilic fluorination of β-ketoester derivatives with HBF4. Chem Commun 48: 12077−12079.CrossRefGoogle Scholar
  41. 41.
    Ohno M, Itoh M, Ohashi T, Eguchi S (1993) Ethyl 3-(1-adamantyl)-2-diazo-3-oxopropanoate: synthetic use for the preparation of some adamantane derivatives. Synthesis 793−796.CrossRefGoogle Scholar
  42. 42.
    Heasley VL, Shellhamer DF, Gipe RK, Wiese HC, Oakes ML, Heasley GE (1980) Reaction of methyl hypochlorite with certain olefins in the presence of boron trifluoride. Tetrahedron Lett 21: 4133−4136.CrossRefGoogle Scholar
  43. 43.
    Heasley VL, Gipe RK, Martin JL, Wiese HC, Oakes ML, Shellhamer DF, Heasley GE, Robinson BL (1983) Boron trifluoride promoted reaction of alkyl hypohalites with alkenes. a new synthesis of fluoro halides. J Org Chem 48: 3195−3199.CrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  1. 1.State Key Laboratory of Organometallic ChemistryShanghai Institute of Organic Chemistry, Chinese Academy of SciencesShanghaiChina