Skip to main content
SpringerLink
Log in

Activation and Formation of Aromatic C–F Bonds

  • Chapter
  • First Online:
Organometallic Fluorine Chemistry

Part of the book series: Topics in Organometallic Chemistry ((TOPORGAN,volume 52))

Abstract

The presence of aryl C–F bonds in pharmaceuticals and agrochemicals is increasing rapidly. Incorporation of a fluorine substituent into biologically relevant molecules yields many benefits such as decreased metabolism, solubility, hydrophobicity and decreased negative side effects. Since there are no known examples of naturally occurring aryl fluorides all must be accessed through chemical synthesis. The formation and activation of aryl C–F bonds is a challenging endeavor, nevertheless several strategies are possible. Recent developments towards the synthesis of fluoroaromatics, as well as routes to selectively remove fluorine from polyfluoroaromatics are surveyed.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 259.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 329.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 329.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

Acac:

Acetylacetonate

ACN:

Acetonitrile

AdBrettPhos:

[3,6-Dimethoxy-2′,4′,6′-tris(1-methylethyl)[1,1′-biphenyl]-2-yl]bis(tricyclo[3.3.1.1]dec-1-yl)-phosphine

Ar:

Aryl

BrettPhos:

2-(Dicyclohexylphosphino)3,6-dimethoxy-2′,4′,6′-triisopropyl-1,1′-biphenyl

Bu:

Butyl

C2:

Carbon 2

cat.:

Catalyst

C–F:

Carbon–fluorine

cod:

1,5-Biscyclooctadiene

Cp:

Cyclopentadienyl

CuF2 :

Cu(II)fluoride

Cy:

Cyclohexyl

°C:

Degrees Celsius

DCE:

Dichloroethane

DCM:

Dichloromethane

DFT:

Density functional theory

DMAP:

Dimethylaminopyridine

DMF:

Dimethylformaldehyde

Dmpe:

Dimethylphosphinoethane

DMSO:

Dimethyl sulfoxide

DPEPhos:

Bis[(2-diphenylphosphino)phenyl]methane

DPPB:

Diphenylphosphinobutane

Ebthi:

Ethylenebis(tetrahydro)indenyl

eq:

Equation

equiv.:

Equivalent

Et:

Ethyl

fac :

Facial

h:

Hours

HEH:

2-Ethylhexyl hydrogen (2-ethylhexyl)phosphonate

iBu:

Isobutyl

KF:

Potassium fluoride

Me:

Methyl

MeOH:

Methanol

MW:

Microwave

NHC:

N-Heterocyclic carbene

NMP:

N-Methyl-2-pyrrolidone

OAc:

Acetate

PET:

Positron emission tomography

Ph:

Phenyl

Pr:

Isopropyl

rt:

Room temperature

TBAF:

Anhydrous tetrabutylammoniumfluoride

tBu:

Tertiary butyl

TEA:

Triethylamine

TEAF:

Tetraethylammonium fluoride

THF:

Tetrahydrofuran

TON:

Turnover number

Triphos:

(Bis(diphenyl)phosphinoehtyl)phenyl phosphine

XeF2 :

Xenon difluoride

References

  1. Muller K, Faeh C, Diederich F (2007) Fluorine in pharmaceuticals: looking beyond intuition. Science 1881–1886. doi:10.1126/science.1131943

    Google Scholar 

  2. Park KB, Kitteringham NR, O’Neill PM (2001) Metabolism of fluorine-containing drugs. Annu Rev Pharmacol Toxicol 41:443–470. doi:10.1146/annurev.pharmtox.41.1.443

    CAS  Google Scholar 

  3. Ametamy SM, Honer M, August Schubiger P (2008) Molecular imaging with PET. Chem Rev 108:1501–1516. doi:10.1021/cr0782426

    Google Scholar 

  4. Hamashima Y, Suzuki T, Takano H, Shimura Y, Sodeoka M (2005) Catalytic enantioselective fluorination of oxindoles. J Am Chem Soc 127:10164–10165. doi:10.1021/ja0513077

    CAS  Google Scholar 

  5. Shimizu M, Hiyama T (2005) Modern synthetic methods for fluorine-substituted target molecules. Angew Chem Int Ed 44:214–231. doi:10.1002/anie.200460441

    CAS  Google Scholar 

  6. Sandford G (2007) Elemental fluorine in organic chemistry. J Fluor Chem 128:90–104. doi:10.1016/j.jfluchem.2006.10.019

    CAS  Google Scholar 

  7. Finger GC, Kruse CW (1956) Aromatic fluorine compounds. VII. Replacement of aromatic –Cl and –NO2 groups by –F1,2. J Am Chem Soc 78:6034–6037. doi:10.1021/ja01604a022

    CAS  Google Scholar 

  8. Grushin V (2007) Processes for preparing fluoroarenes from haloarenes. US Patent 7, 202, 388

    Google Scholar 

  9. Watson DA, Su M, Teverovskiy G, Zhang Y, Garcia-Fortanet J, Kinzel T, Buchwald SL (2009) Formation of ArF from LPdAr(F): catalytic conversion of aryl triflates to aryl fluorides. Science 1661–1664. doi:10.1126/science.1178239

  10. Sing RP, Shreeve JM (2004) Recent highlights in electrophilic fluorination with 1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate). Acc Chem Rev 37:31–44. doi:10.1021/ar030043v

    Google Scholar 

  11. Lagow RJ, Kawa H, DeYoung J (1991) Selective direct fluorination of organolithium and organomagnesium compounds. J Chem Soc Commun 811–812. doi: 10.1039/C39920000811

    Google Scholar 

  12. Snieckus V, Beaulieu F, Mohri K, Han W, Murphy CK, Davis FA (1994) Directed ortho metalation—mediated F+ introduction. Regiospecific synthesis of fluorinated aromatics. Tetrahedron Lett 35:3465–3469. doi:10.1016/S0040-4039(00)73211-4

    CAS  Google Scholar 

  13. Knochel P, Gavryushin A, Yamada S (2010) Convenient electrophilic fluorination of functionalized aryl and heteroaryl magnesium reagents. Angew Chem Int Ed 49:2215–2218. doi:10.1002/anie.200905052

    Google Scholar 

  14. Beller M, Neumann H, Anbarasan P (2010) A new and practical Grignard-coupling–fluorination sequence: synthesis of 2-aryl fluoroarenes. Chem Asian J 5:1775–1778. doi:10.1002/asia.201000288

    Google Scholar 

  15. Beller M, Neumann H, Anbarasan P (2010) Efficient synthesis of aryl fluorides. Angew Chem Int Ed 49:2219–2222. doi:10.1002/anie.200905855

    Google Scholar 

  16. Lothian AP, Ramsden CA (1993) Rapid fluorodesilylation of aryltrimethylsilanes using xenon difuoride: an efficient new route to aromatic fluorides. Synlett 753–755. doi:10.1055/s-1993-22596

    Google Scholar 

  17. Moody DJ, Coe PL, Stuart AM (1998) Fluorodesilylations of fluorophenyltrimethylsilanes with elemental fluorine: discovery of a novel 1,2-migration of the trimethylsilyl group. J Fluor Chem 88:179–184. doi:10.1016/S0022-1139(98)00118-3

    Google Scholar 

  18. Petasis NA, Yudin AK, Zavialov IA, Prakash S, Olah GA (1997) Facile preparation of fluorine-containing alkenes, amides and alcohols via the electrophilic fluorination of alkenyl boronic acids and trifluoroborates. Synlett 5:606–608. doi:10.1055/s-1997-3228

    Google Scholar 

  19. Ritter T, Furuya T (2009) Fluorination of boronic acids mediated by silver(I) triflate. Org Lett 11:2860–2863. doi:10.1021/ol901113t

    Google Scholar 

  20. Lemaire M, Andrioletti B, Métay E, Cazorla C (2009) Metal-free electrophilic fluorination of alkyl trifluoroborates and boronic acids. Tetrahedron Lett 50:3936–3938. doi:10.1016/j.tetlet.2009.04.077

    Google Scholar 

  21. Ritter T, Strom AE, Furuya T (2009) Silver-mediated fluorination of functionalized aryl stannanes. J Am Chem Soc 131:1662–1663. doi:10.1021/ja8086664

    Google Scholar 

  22. Ritter T, Furuya T, Tang P (2010) Silver-catalyzed late-stage fluorination. J Am Chem Soc 132:12150–12154. doi:10.1021/ja105834t

    Google Scholar 

  23. Sanford MS, Anani WQ, Hull KL (2006) Palladium-catalyzed fluorination of carbon-hydrogen bonds. J Am Chem Soc 128:7134–7135. doi:10.1021/ja061943k

    Google Scholar 

  24. Sanford MS, Ball ND (2009) Synthesis and reactivity of a mono-σ-aryl palladium(IV) fluoride. J Am Chem Soc 131:3796–3797. doi:10.1021/ja8054595

    Google Scholar 

  25. Vigalok A, Kaspi AW, Yahev-Levi A, Goldberg I (2008) Xenon difluoride induced aryl iodide reductive elimination: a simple access to difluoropalladium(II) complexes. Inorg Chem 47:5–7. doi:10.1021/ic701722f

    Google Scholar 

  26. Ritter T, Kaiser HM, Furuya T (2008) Palladium-mediated fluorination of arylboronic acids. Angew Chem Int Ed 47:5993–5996. doi:10.1002/anie.200802164

    Google Scholar 

  27. Ritter T, Furuya T (2008) Carbon-fluorine reductive elimination from a high-valent palladium fluoride. J Am Chem Soc 130:10060–10061. doi:10.1021/ja803187x

    Google Scholar 

  28. Yu J-Q, Mei T-S, Wang X (2009) Versatile Pd(OTf)2·2H2O-catalyzed ortho-fluorination using NMP as a promoter. J Am Chem Soc 131:7520–7521. doi:10.1021/ja901352k

    Google Scholar 

  29. Yu J-Q, Chan KSL, Wasa M, Wang X (2011) Palladium(II)-catalyzed selective monofluorination of benzoic acids using a practical auxiliary: a weak-coordination approach. Angew Chem Int Ed 50:9081–9084. doi:10.1002/anie.201102985

    Google Scholar 

  30. Schiemann G, Balz G (1927) Über aromatische Fluorverbindungen, I.: Ein neues Verfahren zu ihrer Darstellung. Ber Dtsch Chem Ges 60:1186–1190. doi:10.1002/cber.19270600539

    Google Scholar 

  31. Gottlieb HB (1936) The replacement of chlorine by fluorine in organic compounds. J Am Chem Soc 58:532–533. doi:10.1021/ja01294a502

    CAS  Google Scholar 

  32. DiMagno SG, Sun H (2006) Room-temperature nucleophilic aromatic fluorination: experimental and theoretical studies. Angew Chem Int Ed 45:2720–2725. doi:10.1002/anie.200504555

    Google Scholar 

  33. Marshall WJ, Grushin VV (2008) Fluorination of nonactivated haloarenes via arynes under mild conditions, resulting from further studies toward Ar−F reductive elimination from palladium(II). Organometallics 27:4825–4828. doi:10.1021/om800520e

    Google Scholar 

  34. Guo R-N, Cai X-F, Shi L, Chen Z-P, Zhou Y-G (2014) Synthesis of fluorinated heteroaromatics through formal substitution of a nitro group by fluorine under transition-metal-free conditions. Chem Eur J 20:8343–8346. doi:10.1002/chem.201402282

    CAS  Google Scholar 

  35. Maimone TJ, Milner PJ, Kinzel T, Zhang Y, Takase MK, Buchwald SL (2011) Evidence for in-situ catalyst modification during the Pd-catalyzed conversion of aryl triflates to aryl fluorides. J Am Chem Soc 133:18106–18109. doi:10.1021/ja208461k

    CAS  Google Scholar 

  36. Noel T, Maimone TJ, Buchwald SL (2011) Accelerating palladium-catalyzed C–F bond formation: use of a microflow packed-bed reactor. Angew Chem Int Ed 50:8900–8903. doi:10.1002/anie.201104652

    CAS  Google Scholar 

  37. Lee HG, Milner PJ, Buchwald SL (2014) Pd-catalyzed nucleophilic fluorination of aryl bromides. J Am Chem Soc 136:3792–3995. doi:10.1021/ja5009739

    CAS  Google Scholar 

  38. Zhao S-B, Wang R-Y, Nguyen H, Becker JJ, Gagné MR (2012) Electrophilic fluorination of cationic Pt-aryl complexes. Chem Commun 48:443–445. doi:10.1039/C1CC15006E

    CAS  Google Scholar 

  39. Fier PS, Hartwig JF (2012) Copper-mediated fluorination of aryl iodides. J Am Chem Soc 134:10795–10798. doi:10.1021/ja304410x

    CAS  Google Scholar 

  40. Ichiishi N, Canty AJ, Yates BF, Sanford MS (2013) Cu-catalyzed fluorination of diaryliodonium salts with KF. Org Lett 15:5134–5137. doi:10.1021/ol4025716

    CAS  Google Scholar 

  41. Hayashi H, Sonoda H, Fukumura K, Nagata T (2002) 2,2-Difluoro-1,3-dimethylimidazolidine (DFI). A new fluorinating agent. Chem Commun 1618–1619. doi:10.1039/B204471D

  42. Nemoto H, Nishiyama T, Akai S (2011) Nucleophilic deoxyfluorination of catechols. Org Lett 13:2714–2717. doi:10.1021/ol200808q

    CAS  Google Scholar 

  43. Tang P, Wang W, Ritter T (2011) Deoxyfluorination of phenols. J Am Chem Soc 133:11482–11484. doi:10.1021/ja2048072

    CAS  Google Scholar 

  44. Betts HM, Robins EG (2014) 2-Bromo-6-[18F]fluoropyridine: two-step fluorine-18 radiolabelling via transition metal-mediated chemistry. J Label Compd Radiopharm 54:215–218. doi:10.1002/jlcr.3147

    Google Scholar 

  45. Ohkubo K, Fujimoto A, Fukuzumi S (2013) Photocatalytic monofluorination of benzene by fluoride via photoinduced electron transfer with 3-cyano-1-methylquinolinium. J Phys Chem A 117:10719–10725. doi:10.1021/jp408315a

    CAS  Google Scholar 

  46. Braun T, Ahrens M, Kohlmann J, Anrens T (2014) Functionalization of fluorinated molecules by transition-metal-mediated C–F bond activation to access fluorinated building blocks. Chem Rev 115:931–972. doi:10.1021/cr500257c (ahead of print)

  47. Senaweera S, Weaver J (2014) C–F activation and functionalization of perfluoro- and polyfluoroarenes. Tetrahedron 70:7413–7428. doi:10.1016/j.tet.2014.06.004

    Google Scholar 

  48. Keyes L, Love JA (2013) Aromatic C–F Activation: converting fluoroarenes to useful building blocks. RSC Catal Ser 11:159–192

    CAS  Google Scholar 

  49. Maron L, Werkema EL, Perrin L, Eisenstein O, Anderson RA (2005) Hydrogen for fluorine exchange in C6F6 and C6F5H by monomeric [1,3,4-(Me3C)3C5H2]2CeH: experimental and computational studies. J Am Chem Soc 124:279–292. doi:10.1021/ja0451012

    Google Scholar 

  50. Deacon GB, Forsyth CM, Junk PC, Wang J (2009) Intramolecular metal–fluorocarbon coordination, C–F bond activation and lanthanoid–fluoride clusters with tethered polyfluorophenylamide ligands. Chem Eur J 15:3082–3092. doi:10.1002/chem.200802294

    CAS  Google Scholar 

  51. Deacon GB, Forsyth CM, Junk PC, Kelly RP, Urbatsch A, Wang J (2012) The effects of light lanthanoid elements (La, Ce, Nd) on (Ar)CF–Ln coordination and C–F activation in N, N-dialkyl-N′-2,3,5,6-tetrafluorophenylethane-1,2-diaminate complexes. Dalton Trans 41:8624–8634. doi:10.1039/C2DT30604B

    CAS  Google Scholar 

  52. Treichel PM, Chaudhari MA, Stone FGA (1963) Chemistry of the metal carbonyls XXII. Pentafluorophenyl derivatives of transition metals. J Organomet Chem 1:98–100. doi:10.1016/S0022-328X(00)80053-4

    CAS  Google Scholar 

  53. Pigolosiewicz IM, Kraft S, Beckhaus R, Haase D, Saak W (2005) Selective C–H and C–F bond activation reactions of pyridine and fluoropyridines—formation of binuclear μ-X titanocene complexes (X = H, F) with α-functionalized N-heterocycles. Eur J Inorg Chem 5:938–945. doi:10.1002/ejic.200400252

    Google Scholar 

  54. Bailey BC, Huffman JC, Mindiola DJ (2007) Intermolecular activation of C−X (X = H, O, F) bonds by a Ti≡CtBu linkage. J Am Chem Soc 129:5302–5303. doi:10.1021/ja0684646

    CAS  Google Scholar 

  55. Andino JG, Fan H, Fout AR, Bailey BC, Baik M-H, Mindiola DJ (2011) 1,2-CF bond activation of perfluoroarenes and alkylidene isomers of titanium. DFT analysis of the C–F bond activation pathway and rotation of the titanium alkylidene moiety. J Organomet Chem 696:4138–4146. doi:10.1016/j.jorganchem.2011.07.037

    CAS  Google Scholar 

  56. Fout AR, Scott J, Miller DL, Bailey BC, Pink M, Mindiola DJ (2009) Dehydrofluorination of hydrofluorocarbons by titanium alkylidynes via sequential C−H/C−F bond activation reactions. A synthetic, structural, and mechanistic study of 1,2-CH bond addition and β-fluoride elimination. Oraganometallics 28:331–337. doi:10.1021/om800910q

    CAS  Google Scholar 

  57. Guo H, Kong F, Kanno K-I, He J, Nakajima K, Takahasi T (2006) Early transition metal-catalyzed cross-coupling reaction of aryl fluorides with a phenethyl Grignard reagent accompanied by rearrangement of the phenethyl group. Organometallics 25:2045–2048. doi:10.1021/om0511027

    CAS  Google Scholar 

  58. Podolan G, Lentz D, Reissig H-U (2013) Selective catalytic hydrodefluorination as a key step for the synthesis of hitherto inaccessible aminopyridine derivatives. Angew Chem Int Ed 52:9491–9494. doi:10.1002/anie.201301927

    CAS  Google Scholar 

  59. Kuehnel MF, Holstein P, Kliche M, Krüger J, Matthies S, Nitsch D, Schutt J, Sparenberg M, Lentz D (2012) Titanium-catalyzed vinylic and allylic C–F bond activation-scope, limitations and mechanistic insight. Chem Eur J 18:10701–10714. doi:10.1002/chem:201201125

  60. Edelbach BL, Fazlur Rahman AK, Lachicotte RJ, Jones WD (1999) Carbon-fluorine bond cleavage by zirconium metal hydride complexes. Organometallics 18:3170–3177. doi:10.1021/om9902481

    CAS  Google Scholar 

  61. Jäger-Fiedler U, Arndt P, Baumann W, Spannenberg A, Burlakov VV, Rosenthal U (2005) Reactions of zirconocene bis(trimethylsilyl)acetylene complexes with fluorinated pyridines: C–H vs. C–F bond activation. Eur J Inorg Chem 2005:2842–2849. doi:10.1002/ejic.200500145

    Google Scholar 

  62. Hoyt HM, Micheal FE, Bergman RG (2004) C-H bond activation of hydrocarbons by an imidozirconocene complex. J Am Chem Soc 126:1018–1019. doi:10.1021/ja0385944

    CAS  Google Scholar 

  63. Jäger-Fiedler U, Klahn M, Arndt P, Baumann W, Spannenber A, Burlakov VV, Rosenthal U (2007) Room-temperature catalytic hydrofluorination of pentafluoro-pyridine by zirconocene fluoro complexes and diisobutylaluminum hydride. J Mol Catal A Chem 261:184–189. doi:10.1016/j.molcata.2006.06.027

    Google Scholar 

  64. Yow SY, Gates SJ, White AJP, Crimmi MR (2012) Zirconocene dichloride catalyzed hydrofluorination of Csp2 bonds. Angew Chem Int Ed 51:12559–12563. doi:10.1002/anie.201207036

    CAS  Google Scholar 

  65. Schrock RR, Adamchuk J, Ruhland K, Lopez LPH (2003) Zirconium and Hafnium complexes that contain the electron-withdrawing diamido/donor ligands [(2,6-X2C6H3NCH2)2C(2-C5H4N)(CH3)]2- (X=Cl or F). An evaluation of the role of ortho halides in 1-hexene polymerization. Organometallics 22:5079–5091. doi:10.1021/om0305364

    CAS  Google Scholar 

  66. Cahiez G (1999) Manganese-catalyzed substitution of activated aryl halides (X=Cl, Br and F) and aryl ethers by organomagnesium reagents. Synthesis 12:2138–2144. doi:10.1055/s-1999-3644

    Google Scholar 

  67. Vela J, Smith JM, Yu Y, Ketterer NA, Flashernriem CJ, Lachicotte RJ, Holland PL (2005) Synthesis and reactivity of low-coordinate iron(II) fluoride complexes and their use in the catalytic hydrodefluorination of fluorocarbons. J Am Chem Soc 127:7857–7870. doi:10.1021/ja042672l

    CAS  Google Scholar 

  68. Whittlesey MK, Perutz RN, Moore MH (1996) Facile intermolecular aromatic C–F bond activation reaction of [Ru(dmpe)2H2](dmpe=Me2PCH2CH2PMe2). Chem Commun 787–788. doi:10.1039/CC9960000787

  69. Whittlesey MK, Perutz RN, Greener B, Moore MH (1997) Synthesis, molecular structure and NMR spectroscopy of a transition-metal bifluoride complex: formation via C–F activation or reaction with Et3N·3HF. Chem Commun 187–188 doi:10.1039/A606598H

    Google Scholar 

  70. Reade SP, Acton AL, Mahon MF, Martin TA, Whittlesey MK (2009) Synthesis and reactivity of Ru(NHC)(dppp)(CO)H2 and Ru(NHC)(dppp)(CO)HF complexes: C–H and C–F activation. Eur J Inorg Chem 2009:1774–1785. doi:10.1002/ejic.200801105

    Google Scholar 

  71. Reade SP, Mahon MF, Whittlesey MK (2009) Catalytic hydrodefluorination of aromatic fluorocarbons by ruthenium N-heterocyclic carbene complexes. J Am Chem Soc 131:1847–1861. doi:10.1021/ja806545e

    CAS  Google Scholar 

  72. Kawamoto K, Takuya K, Sato M, Mizushima E, Kakiuchi F (2011) Ruthenium-catalyzed arylation of fluorinated aromatic ketones via ortho-selective carbon-fluorine bond cleavage. Tetrahedron Lett 52:5888–5890. doi:10.1016/j.tetlet.2011.09.005

    CAS  Google Scholar 

  73. Korn TJ, Schade MA, Wirth S, Knochel P (2006) Cobalt(II)-catalyzed cross-coupling between polyfunctional arylcopper reagents and aryl fluorides or tosylates. Org Lett 8:725–728. doi:10.1021/ol0529142

    CAS  Google Scholar 

  74. Zheng T, Sun H, Chen Y, Li X, Dürr S, Radius U, Harms R (2009) Synergistic effect of a low-valent cobalt complex and a trimethylphosphine ligand on selective C−F bond activation of perfluorinated toluene. Organometallics 28:5771–5776. doi:10.1021/om900589z

    CAS  Google Scholar 

  75. Zheng T, Sun H, Ding J, Zhang Y, Li X (2010) Effect of anchoring group and valent of cobalt center on the competitive cleavage of C–F or C–H bond activation. J Organomet Chem 695:1873–1877. doi:10.1016/j.jorganchem.2010.04.031

    CAS  Google Scholar 

  76. Li J, Zheng T, Sun H, Xu W, Li X (2013) Selective C–F/C–H bond activation of fluoroarenes by cobalt complex supported with phosphine ligands. Dalton Trans 42:5740–5748. doi:10.1039/c3dt33074e

    CAS  Google Scholar 

  77. Li J, Zheng T, Sun H, Li X (2013) Selectively catalytic hydrodefluorination of perfluoroarenes by Co(PMe3)4 with sodium formate as reducing agent and mechanism study. Dalton Trans 42:13048–13053. doi:10.1039/c3dt50409c

    CAS  Google Scholar 

  78. Lu F, Li J, Sun H, Li X (2014) Selective C-H bond activation of 1,2,4,5-tetrafluorobenzene by Co(PMe3)4. Inorg Chim Acta 416:222–225. doi:10.1016/j.ica.2014.03.025

    CAS  Google Scholar 

  79. Dugan TR, Goldberg JM, Brennessel WW, Holland PL (2012) Low-coordinate cobalt fluoride complexes. synthesis, reactions, and production from C–F activation reactions. Organometallics 31:1349–1360. doi:10.1021/om200991k

    CAS  Google Scholar 

  80. Jones WD, Partridge MG, Perutz RN (1991) Sequential arene coordination and C-F insertion in the reactions of (η5-pentamethylcyclopentadienyl)rhodium complexes with hexafluorobenzene. J Chem Soc Chem Commun 264–266. doi:10.1039/C39910000264

    Google Scholar 

  81. Edelbach BL, Jones WD (1997) Mechanism of carbon−fluorine bond activation by (C5Me5)Rh(PMe3)H2. J Am Chem Soc 119:7734–7742. doi:10.1021/ja970723r

    CAS  Google Scholar 

  82. Grushin VV, Marshall WJ (2004) The fluoro analogue of Wilkinson’s catalyst and unexpected Ph−Cl activation. J Am Chem Soc 126:3068–3069. doi:10.1021/ja049844z

    CAS  Google Scholar 

  83. Noveski D, Braun T, Neumann B, Stammler A, Stammler H-G (2004) C–F or C–H bond activation and C–C coupling reactions of fluorinated pyridines at rhodium: synthesis, structure and reactivity of a variety of tetrafluoropyridyl complexes. Dalton Trans 4106-4119. doi:10.1039/B414734K

  84. Braun T, Noveski D, Ahijado M, Wehmeier F (2007) Hydrodefluorination of pentafluoropyridine at rhodium using dihydrogen: detection of unusual rhodium hydrido complexes. Dalton Trans 3820–3825. doi:10.1039/B706846H

    Google Scholar 

  85. Lindup RJ, Marder TB, Perutz RN, Whitwood AC (2007) Sequential C–F activation and borylation of fluoropyridines via intermediate Rh(I) fluoropyridyl complexes: a multinuclear NMR investigation. Chem Commun 3664–3666. doi:10.1039/B707840D

    Google Scholar 

  86. Lena Raza A, Panetier JA, Teltewskoi M, Macgregor SA, Braun T (2013) Rhodium(I) silyl complexes for C–F bond activation reactions of aromatic compounds: experimental and computational studies. Organometallics 32:3795–3807. doi:10.1021/om400150p

    Google Scholar 

  87. Aizenburg M, Milstein D (1994) Catalytic activation of carbon-fluorine bonds by a soluble transition metal complex. Science 359–361. doi:10.1126/science.265.5170.359

  88. Aizenburg M, Milstein D (1995) Homogenous rhodium complex-catalyzed hydrogenolysis of C–F bonds. J Am Chem Soc 117:8674–8675. doi:10.1021/ja00138a027

    Google Scholar 

  89. Young RJ Jr, Grushin VV (1999) Catalytic C–F bond activation and nonactivated monofluoroarenes. Organometallics 18:294–296. doi:10.1021/om980887w

    CAS  Google Scholar 

  90. Ihii Y, Chatani N, Yorimitsu S, Murai S (1998) Rhodium-catalyzed Si-F exchange reaction between fluorobenzenes and a disilane. Catalytic reaction involving cleavage of C–F bonds. Chem Lett 27:157–158. doi:10.1246/cl.1998.157

    Google Scholar 

  91. Arisawa M, Suzuki T, Ishikawa T, Yamaguchi M (2008) Rhodium-catalyzed substitution reaction of aryl fluorides with disulfides: p-orientation in the polyarylthiolation of polyfluorobenzenes. J Am Chem Soc 130:12214–12215. doi:10.1021/ja8049996

    CAS  Google Scholar 

  92. Teltewskoi M, Panetier JA, Macgregor SA, Braun T (2010) A highly reactive rhodium(I)–boryl complex as a useful tool for C-H bond activation and catalytic C–F bond borylation. Angew Chem Int Ed 49:3947–3951. doi:10.1002/anie.201001070

    CAS  Google Scholar 

  93. Chan PK, Leong WK (2008) Reaction of Cp*Ir(CO)2 with activated perfluoroaromatic compounds: formation of metallocarboxylic acids via aromatic nucleophilic substitution. Organometallics 27:1247–1253. doi:10.1021/om701078q

    CAS  Google Scholar 

  94. Fahey DR, Mahan JE (1977) Oxidative additions of aryl, vinyl, and acyl halides to triethylphosphinenickel(0) complexes. J Am Chem Soc 99:2501–2508. doi:10.1021/ja00450a017

    CAS  Google Scholar 

  95. Jasim NA, Perutz RN, Whitwood AC, Braun T, Izundu J, Neumann B, Rothfeld S, Stammler H-G (2004) Contrasting reactivity of fluoropyridines at palladium and platinum: C−F oxidative addition at palladium, P−C and C−F activation at platinum. Organometallics 23:6140–6149. doi:10.1021/om049448p

    CAS  Google Scholar 

  96. Cruise SJ, Taylor ET, Johnson SA (2009) A combined experimental and computational study of unexpected C–F bond activation intermediates and selectivity in the reaction of pentafluorobenzene with a (Pet3)2Ni synthon. Organometallics 28:3842–3855. doi:10.1021/om900176v

    Google Scholar 

  97. Saliba M, Mustafa F, Huff CW, Johnson SA (2008) Unexpected intermediates and products in the C–F bond activation tetrafluorobenzenes with a bis(triethylphosphine)nickel synthon: direct evidence of a rapid and reversible C-H bond activation by Ni(0). J Am Chem Soc 130:17278–17280. doi:10.1021/ja8081395

    Google Scholar 

  98. Murray S, Valdizon R, Mroz NM, Johnson SA (2011) Characterization of intermediates in the C–F activation of tetrafluorobenzenes using a reactive Ni(Pet3)2 synthon: combined computational and experimental investigation. Organometallics 30:441–457. doi:10.1021/om100699d

    Google Scholar 

  99. Hatnean JA, Johnson SA (2012) Experimental study of the reaction of a Ni(PEt3)2 synthon with polyfluorinated pyridines: concerted, phosphine-assisted, or radical C–F bond activation mechanisms? Organometallics 31:1361–1373. doi:10.1021/om200990g

    CAS  Google Scholar 

  100. Sladek MI, Braun T, Neumann B, Stammler H-G (2002) Aromatic C–F activation at Ni in the presence of a carbon–chlorine bond: the nickel mediated synthesis of new pyrimidines. J Chem Soc Dalton Trans 297–299. doi:10.1039/B110128E

    Google Scholar 

  101. Steffan A, Sladek MI, Braun R, Neumann B, Stammler H-G (2005) Catalytic C−C coupling reactions at nickel by C−F activation of a pyrimidine in the presence of a C−Cl bond: the crucial role of highly reactive fluoro complexes. Organometallics 24:4057–4064. doi:10.1021/om050080l

    Google Scholar 

  102. Breyer D, Berger J, Braun T, Mebs S (2012) Nickel fluoro complexes as intermediates in catalytic cross-coupling reactions. J Fluor Chem 143:263–271. doi:10.1016/j.jfluchem.2012.06.025

    CAS  Google Scholar 

  103. Schaub T, Radius U (2005) Efficient C–F and C–C activation by a novel N-heterocyclic carbene–nickel(0) complex. Chem Eur J 11:5024–5030. doi:10.1002/chem.200500231

    CAS  Google Scholar 

  104. Schaub T, Fischer P, Steffan A, Braun T, Radius U, Mix A (2008) C−F activation of fluorinated arenes using NHC-stabilized nickel(0) complexes: selectivity and mechanistic investigations. J Am Chem Soc 130:9304–9317. doi:10.1021/ja074640e

    CAS  Google Scholar 

  105. Doster ME, Johnson SA (2009) Selective C–F bond activation of tetrafluorobenzenes by nickel(0) with a nitrogen donor analogous to N-heterocyclic carbenes. Angew Chem Int Ed 48:2185–2187. doi:10.1002/anie.200806048

    CAS  Google Scholar 

  106. Kiso Y, Tomao K, Kumada M (1973) Effects of the nature of halides on the alkyl group isomerization in the nickel-catalyzed cross-coupling of secondary alkyl Grignard reagents with organic halides. J Organomet Chem 50:C12–C14. doi:10.1016/S0022-328X(00)95063-0

    CAS  Google Scholar 

  107. Tomao K, Sumitani K, Kiso Y, Zembayashi M, Fujuoka A, Kodama S-I, Nakajima I, Minato A, Kumada M (1976) Nickel-phosphine complex-catalyzed Grignard coupling I. Cross-coupling of alkyl, aryl, and alkenyl Grignard reagents with aryl and alkenyl halides: general scope and limitations. Bull Chem Soc Jpn 49:1958–1969. http://dx.doi.org/10.121246/bcsj.49.1958

  108. Mongin F, Mojovic L, Guillamet B, Trécourt F, Quéguiner G (2002) Cross-coupling reactions of phenylmagnesium halides with fluoroazines and fluorodiazines. J Org Chem 67:8991–8994. doi:10.1021/jo026136s

    CAS  Google Scholar 

  109. Saeki T, Takashima Y, Tomao K (2005) Nickel- and Palladium-catalyzed cross-coupling reaction of polyfluorinated arenes and alkenes with Grignard reagents. Synlett 1771–1774. doi:10.1055/s-2005-871571

    Google Scholar 

  110. Braun T, Perutz RN, Sladek MI (2001) Catalytic C-F activation of polyfluorinated pyridines by nickel-mediated cross-coupling reactions. Chem Commun 2254–2255. doi:10.1039/B106646C

    Google Scholar 

  111. Yoshikai N, Matsuda H, Nakamura E (2009) Hydroxyphosphine ligand for nickel-catalyzed cross-coupling through nickel/magnesium bimetallic cooperation. J Am Chem Soc 131:9590–9599. doi:10.1021/ja903091g

    CAS  Google Scholar 

  112. Nakamura Y, Yoshikai N, IIlies L, Nakamura E (2012) Nickel-catalyzed monosubstitution of polyfluoroarenes with organozinc reagents using alkoxydiphosphine ligand. Org Lett 14:3316–3319. doi:10.1021/ol301195x

    CAS  Google Scholar 

  113. Asako S, IIlies L, Verma P, Ichikawa S, Nakamura E (2014) Theoretical study on alkoxydiphosphine ligand for bimetallic cooperation in nickel-catalyzed monosubstitution of C–F bond. Chem Lett 43:726–728. doi:10.1246/cl.131205

    CAS  Google Scholar 

  114. Ackermann L, Wechsler C, Kapdi AR, Althammer A (2010) Air-stable diaminophosphine sulfides as preligands for nickel-catalyzed cross-couplings of unactivated fluoro(hetero)arenes. Synlett 294–298. doi:10.1055/s-0029-1219166

    Google Scholar 

  115. Sun AD, Love JA (2011) Nickel-catalyzed selective defluorination to generate partially fluorinated biaryls. Org Lett 13:2750–2753. doi:10.1021/ol200860t

    CAS  Google Scholar 

  116. Tobisu M, Xu T, Shimasaki T, Chatani N (2011) Nickel-catalyzed Suzuki-Miyaura reaction of aryl fluorides. J Am Chem Soc 133:19505–19511. doi:10.1021/ja207759e

    CAS  Google Scholar 

  117. Sun AD, Leung K, Restivo AD, LaBerge NA, Takasaki H, Love JA (2014) Nickel-catalyzed Csp2-Csp3 bond formation by carbon-fluorine activation. Chem Eur J 20:3162–3168. doi:10.1002/chem.201303809

    CAS  Google Scholar 

  118. Xiuxiu Y, Sun H, Zhang S, Li X (2013) Nickel-catalyzed C–F bond activation and alkylation of polyfluoroaryl imines. J Organomet Chem 723:36–42

    Google Scholar 

  119. Zhu F, Wang Z-X (2014) Nickel-catalyzed cross-coupling of aryl fluorides and organozinc reagents. J Org Chem 79:4285–4292. doi:10.1021/jo5006191

    CAS  Google Scholar 

  120. Yu D, Wang C-S, Yao C, Shen Q, Lu L (2014) Nickel-catalyzed α-arylation of zinc enolates with polyfluoroarenes via C–F bond activation under neutral conditions. Org Lett 16:5544–5547. doi:10.1021/o1502499q

    CAS  Google Scholar 

  121. Böhm VPW, Gstöttmayr CWK, Weskamp T, Herrmann WA (2001) Catalytic C−C bond formation through selective activation of C−F bonds. Angew Chem Int Ed 40:3387–3389. doi:10.1002/1521-3773(20010917)40:18<3387::AID-ANIE3387>3.0.CO;2-6

    Google Scholar 

  122. Schaub T, Backes M, Radius U (2006) Catalytic C-C bond formation accomplished by selective C–F activation of perfluorinated arenes. J Am Chem Soc 128:15964–15965. doi:10.1021/ja064068b

    CAS  Google Scholar 

  123. Fischer P, Götz K, Eichhorn A, Radius U (2012) Decisive steps of the hydrodefluorination of fluoroaromatics using [Ni(NHC)2]. Organometallics 31:1374–1383. doi:10.1021/om2009815

    CAS  Google Scholar 

  124. Zhao W, Wu J, Cao S (2012) Highly efficient nickel(II) chloride/bis(tricyclohexylphosphine)nickel(II) chloride-cocatalyzed hydrodefluorination of fluoroarenes and trifluorotoluenes with superhydride. Adv Synth Catal 354:574–585. doi:10.1002/adsc.201100783

    CAS  Google Scholar 

  125. He T, Chen Z, He C-Y, Zhang X (2013) Nickel-catalyzed ortho-selective hydrodefluorination of N-containing heterocycle-polyfluoroarenes. Chin J Chem 31:873–877

    CAS  Google Scholar 

  126. Arévalo A, Tlahuext-Aca A, Flores-Alamo M, García JJ (2014) On the catalytic hydrodefluorination of fluoroaromatics using nickel complexes: the true role of the phosphine. J Am Chem Soc 136:4634–4639. doi:10.1021/ja412268y

    Google Scholar 

  127. Nova A, Reinhold M, Perutz RN, Macgregor SA, McGrady JE (2010) Selective activation of the ortho C−F bond in pentafluoropyridine by zerovalent nickel: reaction via a metallophosphorane intermediate stabilized by neighboring group assistance from the pyridyl nitrogen. Organometallics 29:1824–1831. doi:10.1021/om100064z

    CAS  Google Scholar 

  128. Nova A, Erhardt S, Jasim N, Perutz RN, Macgregor SA, McGrady JE, Whitwood AC (2008) Competing C–F activation pathways in the reaction of Pt(0) with fluoropyridines: phosphine-assistance versus oxidative addition. J Am Chem Soc 130:15499–15511. doi:10.1021/ja8046238

    CAS  Google Scholar 

  129. Braun T, Izundu J, Steffan A, Neumann B, Stammler H-G (2006) Reactivity of a palladium fluoro complex towards silanes and Bu3SnCH=CH2: catalytic derivatisation of pentafluoropyridine based on carbon–fluorine bond activation reactions. Dalton Trans 5118–5123. doi:10.1039/B608410A

    Google Scholar 

  130. Breyer D, Braun T, Kläring P (2012) Synthesis and reactivity of the fluoro complex trans-[Pd(F)(4-C5NF4)(iPr2PCH2CH2OCH3)2]: C–F bond formation and catalytic C–F bond activation reactions. Organometallics 31:1417–1424. doi:10.1021/om200998d

    CAS  Google Scholar 

  131. Cargill MR, Sandford G, Tadeusiak AJ, Yufit DS, Howard JAK, Kilickiran P, Nelles G (2010) Palladium-catalyzed C−F activation of polyfluoronitrobenzene derivatives in Suzuki−Miyaura coupling reactions. J Org Chem 75:5860–5866. doi:10.1021/jo100877j

    CAS  Google Scholar 

  132. Yu D, Shen Q, Lu L (2012) Selective palladium-catalyzed C–F activation/carbon-carbon bond formation of polyfluoroaryl oxazolines. J Org Chem 77:1798–1804. doi:10.1021/jo2023262

    CAS  Google Scholar 

  133. Yu D, Lu L, Shen Q (2013) Palladium-catalyzed coupling of polyfluorinated arenes with heteroarenes via C–F/C–H activation. Org Lett 15:940–943. doi:10.1021/ol303567t

    CAS  Google Scholar 

  134. Chen Z, He C-Y, Yin Z, Chen L, He Y, Zhang X (2013) Palladium-catalyzed ortho-selective C–F activation of polyfluoroarenes with triethylsilane: a facile access to partially fluorinated aromatics. Angew Chem Int Ed 52:5813–5817. doi:10.1002/anie.201300400

    CAS  Google Scholar 

  135. Sun L, Rong M, Kong D, Dai Z, Yuan Y, Weng Z (2013) Synthesis of polyfluorinated aryl ethers via ligand-free palladium-catalyzed C–F activation of pentafluorobenzene. J Fluor Chem 150:117–123. doi:10.1016/j.jfluchem.2013.02.025

    CAS  Google Scholar 

  136. Ohashi M, Doi R, Ogoshi S (2014) Palladium-catalyzed coupling reaction of perfluoroarenes with diarylzinc complexes. Chem Eur J 20:2040–2048. doi:10.1002/chem201203451

  137. Crespo M, Martinez M, Sales J (1993) Effect of fluorine substituents in intramolecular activation of carbon-fluorine and carbon-hydrogen bonds by platinum(II). Organometallics 12:4297–4304. doi:10.1021/om00035a014

    CAS  Google Scholar 

  138. Crespo M, Solans X, Font-Bardia M (2005) Cyclometalated platinum(II) compounds with fluorinated iminic ligands: synthesis and reactivity tuning. crystal structures of the compounds [PtMe(RCH:NCH2C6H5)(PPh3)] (R=2,3,4-C6HF3 and 2,3-C6H2F2). Organometallics 14:355–364. doi:10.1021/om00001a051

    Google Scholar 

  139. López O, Crespo M (1997) Activation of C−F and C−H bonds by platinum in trifluorinated [C, N, N′] ligands. Crystal structures of [PtFMe2{Me2NCH2CH2NHCH(CH2COMe)(2,4–C6H2F2)}] and [PtMe{Me2NCH2CH2N=CH(2,3,4–C6HF3)}]. Organometallics 16:1233–1240. doi:10.1021/om960803o

    Google Scholar 

  140. Nova A, Mas-Ballesté R, Ujaque G, González-Duarte P, Lledós A (2009) Aromatic C–F activation by complexes containing the {Pt2S2} core via nucleophilic substitution: a combined experimental and theoretical study. Dalton Trans 5980–5988. doi:10.1039/B901697J

    Google Scholar 

  141. Schwartsburd L, Cohen R, Konstantinovski L, Milstein D (2008) A pincer-type anionic platinum(0) complex. Angew Chem Int Ed 47:3603–3606. doi:10.1002/anie.200705927

    CAS  Google Scholar 

  142. Wang T, Alfonso BJ, Love JA (2007) Platinum(II)-catalyzed cross-coupling of polyfluoroaryl imines. Org Lett 9:5629–5631. doi:10.1021/ol702591b

    CAS  Google Scholar 

  143. Buckley HL, Wang T, Tran O, Love JA (2009) Selective platinum-catalyzed C–F bond activation as a route to fluorinated aryl methyl ethers. Organometallics 28:2356–2359. doi:10.1021/om900100f

    CAS  Google Scholar 

  144. Keyes L, Sun AD, Love JA (2011) Exploration of the scope of Pt-catalyzed C–F activation. Eur J Org Chem 2011:3985–3994. doi:10.1002/ejoc.201100478

    CAS  Google Scholar 

  145. Wang T, Keyes L, Patrick BO, Love JA (2012) Exploration of the mechanism of platinum(II)-catalyzed C–F activation: characterization and reactivity of platinum(IV) fluoroaryl complexes relevant to catalysis. Organometallics 31:1397–1407. doi:10.1021/om2007562

    CAS  Google Scholar 

  146. Wang T, Love JA (2008) Insight into the mechanism of platinum-catalyzed cross-coupling of polyfluoroaryl imines. Organometallics 27:3290–3296. doi:10.1021/om800247p

    CAS  Google Scholar 

  147. Cao L, Liu C, Tang X, Yin X, Zhang B (2014) Highly selective synthesis of 1-polyfluoroaryl-1,2,3-triazoles via a one-pot three component reaction. Tetrahedron Lett 55:5033–5037. doi:10.1016/j.tetlet.2014.07.041

    CAS  Google Scholar 

  148. Lu H, Zhan J-H, Cai Y-B, Yu Y, Wang B, Zhang J-L (2012) π–π Interaction assisted hydrodefluorination of perfluoroarenes by gold hydride: a case of synergistic effect on C–F bond activation. J Am Chem Soc 134:16216–16227. doi:10.1021/ja305204y

    Google Scholar 

  149. Zhan J-H, Lv H, Yu Y, Zhang J-L (2012) Catalytic C–F bond activation of perfluoroarenes by tricoordinated gold(I) complexes. Adv Synth Catal 354:1529–1541. doi:10.1002/adsc.201100843

    CAS  Google Scholar 

  150. Liu C, Cao L, Yin X, Xu H, Zhang B (2013) Selective C4-F bond cleavage/C-O bond formation of polyfluoroarenes with phenols and benzyl alcohols. J Fluor Chem 156:51–60. doi:10.1016/j.jfluchem.2013.08.013

    CAS  Google Scholar 

  151. Xiong Y, Wu J, Xiao S, Xiao J, Cao S (2013) Noncatalytic pyridyl-directed alkylation and arylation carbon-fluorine bond of polyfluoroarenes with grignard reagents. J Org Chem 78:4599–4603. doi:10.1021/jo400424d

    CAS  Google Scholar 

  152. Lu F, Sun H, Du A, Feng L, Li X (2014) Selective alkylation and arylation of C–F bond with Grignard reagents. Org Lett 16:772–775. doi:10.1021/ol403479r

    CAS  Google Scholar 

  153. Borah HN, Prajapati D, Boruah RC (2005) A novel indium-catalyzed sonogashira coupling reaction, effected in the absence of a copper salt, phosphine ligand and palladium. Synlett 2823–2825. doi:10.1055/s-2005-918948

    Google Scholar 

  154. Allemann O, Duttwyler S, Romanato P, Baldridge KK, Siegel JS (2011) Proton-catalyzed, silane-fueled friedel-crafts coupling of fluoroarenes. Science 574–577. doi:10.1126/science.1202432

    Google Scholar 

  155. Jana A, Samuel PP, Tavčar G, Roesky HW, Schulzke C (2010) Selective aromatic C–F and C–H bond activation with silylenes of different coordinate silicon. J Am Chem Soc 132:10164–10170. doi:10.1021/ja103988d

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Chemistry, University of British Columbia, 2036 Main Mall, Vancouver, BC, Canada, V6T 1Z1

    Nicole A. LaBerge & Jennifer A. Love

Authors
  1. Nicole A. LaBerge
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jennifer A. Love
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jennifer A. Love .

Editor information

Editors and Affiliations

  1. Institut für Chemie, Humboldt-Universität zu Berlin, Berlin, Germany

    Thomas Braun

  2. Dartmouth College, Hanover, New Hampshire, USA

    Russell P. Hughes

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer International Publishing Switzerland

About this chapter

Cite this chapter

LaBerge, N.A., Love, J.A. (2015). Activation and Formation of Aromatic C–F Bonds. In: Braun, T., Hughes, R. (eds) Organometallic Fluorine Chemistry. Topics in Organometallic Chemistry, vol 52. Springer, Cham. https://doi.org/10.1007/3418_2015_90

Download citation

Publish with us

Policies and ethics

Search

Navigation