Group IV metallocene-mediated synthesis of fluoroaromatics via selective defluorination of saturated perfluorocarbons

Full text of DOI:10.1021/ja952563u

J. Am. Chem. Soc. 1996, 118, 1805-1806
1805
The key feature of this work is the use of early transition
metallocenes to mediate electron transfer from readily available
terminal reductants such as magnesium and aluminum metals.
Zirconocene complexes have become firmly entrenched in
the application of organometallic reagents in organic synthesis;12
however, examples of their chemistry with fluorocarbons are
rare.4 This can be attributed to the great strength of the early
transition metal-fluoride bond which is thought to preclude
catalytic chemistry. Thus, the key challenge in early transition
metal organometallic fluorocarbon chemistry is not merely
breaking a C-F bond but developing a system in which catalytic
turnover is possible.13
As depicted in eq 1, reaction of 6.2 mmol of perfluorodecalin
(1) with 0.026 mmol of Cp2TiF2 in the presence of excess Al
(87 mmol)/HgCl2 (0.19 mmol) as the terminal reductant in THF
solution at room temperature results in catalytic production of
octafluoronaphthalene (2) (3.2 mmol, 12 turnovers).14 Over 120
Group IV Metallocene-Mediated Synthesis of
Fluoroaromatics via Selective Defluorination of
Saturated Perfluorocarbons
Jaqueline L. Kiplinger and Thomas G. Richmond*
Department of Chemistry, UniVersity of Utah
Salt Lake City, Utah 84112
ReceiVed July 31, 1995
Fluorocarbons are noted for their chemical inertness, which
is a manifestation of the great strength of the C-F bond and
the weak nature of metal fluorocarbon interactions. These same
thermodynamic and kinetic considerations which tend to disfavor
C-F activation have also been exploited in useful technological
and medical applications of fluorocarbons.1 A recent example
is the development of the “fluorous biphase system” by Horva´th
and Ra´bai at Exxon2 in which the low hydrocarbon solubility
of catalysts decorated with perfluoroalkyl chains allows for facile
separation of products from catalysts under homogeneous
conditions.
Activation and functionalization of C-F bonds provides a
chemical challenge akin to that of C-H activation in analogous
hydrocarbon compounds. Although it is well known that strong
reducing agents such as sodium in liquid ammonia can
completely destroy fluorocarbons to afford carbon and fluoride
ions,3 the crucial problem is one of selectiVe activation of C-F
bonds rather than complete defluorination. In the past decade,
numerous examples of C-F bond activation using organome-
tallic complexes have been reported,4 but only recently has
homogeneous catalytic hydrogenation of a C-F bond been
noted.5 Like nearly all examples of C-F activation, this latter
work utilizes hexafluorobenzene as a substrate. Homogeneous
reaction chemistry of saturated perfluorocarbons is limited to
complete defluorination using aryl thiolates,6 substoichiometric
reactions with [CpFe(CO)2]-,7 Cp2Co,8 or alkali metal organic
radical anions,9 and radical-based hydrogen for fluorine ex-
change using Cp3UCMe3.10 Most recently, Crabtree and co-
workers11 have combined NH3 with Hg photosensitization to
reduce and functionalize saturated perfluorocarbons. We report
here the first examples of transition metal-catalyzed synthesis
of perfluoroaromatic compounds by room temperature reductive
defluorination of saturated perfluorocarbons. In addition, a mild
hydrogenation of aromatic carbon-fluorine bonds is reported.
fluorides are removed per titanium metal center, and Cp2TiF2
can be recovered from the reaction mixture. It is important to
note that initial activation of the fluorocarbon appears to be the
slow step in this reaction because unreacted starting material
can be recovered with subsequent defluorination and formation
of the aromatic products as rapid events. Control experiments
demonstrate that the metallocene fragment is necessary for the
observed chemistry since the activated aluminum does not
exhibit any reactivity with perfluorodecalin or perfluoronaph-
thalene at room temperature. The Cp2TiF2-mediated chemistry
can be extended to other ring systems such as perfluoro-
(tetradecahydrophenanthrene) (3) to afford decafluorophenan-
threne (4) (eq 2). Our studies also show that Cp2ZrCl2 and
(1) (a) Organofluorine Chemistry: Principles and Commercial Applica-
tions; Banks, R. E., Smart, B. E., Tatlow, J. C., Eds.; Plenum: New York,
1994. (b) Chemistry of Organic Fluorine Compounds II. A Critical ReView;
Hudlicky, M., Pavlath, A. E., Eds.; ACS Monograph 187; American
Chemical Society: Washington, DC, 1995; and references therein.
(2) Horva´th, I. T.; Ra´bai, J. Science 1994, 266, 72-75.
(3) Miller, J. F.; Hunt, H.; McBee, E. T. Anal. Chem. 1947, 19, 148-
149.
Cp2ZrF2 (in the presence of Mg/HgCl2) are equally effective in
mediating the tranformation depicted in eq 1.15 However, these
reactions tend to be rather exothermic, and so great care should
be exercised when the chemistry is performed on large scales.
The important observation that Cp2TiF2 and Cp2ZrF2 can
mediate these transformations provides evidence that early
transition metal fluoride complexes do not preclude catalytic
chemistry.
(4) For a comprehensive review of C-F activation by metal reagents,
see: Kiplinger, J. L.; Richmond, T. G.; Osterberg, C. E. Chem. ReV. 1994,
94, 373-431.
(5) Aizenberg, M.; Milstein, D. Science 1994, 265, 359-361.
(6) (a) MacNicol, D. D.; Robertson, C. D. Nature 1988, 332, 59-61.
(b) MacNicol, D. D.; McGregor, W. M.; Mallinson, P. R.; Robertson, C.
D. J. Chem. Soc., Perkin Trans. 1991, 3380-3382.
(12) (a) Cardin, D. J.; Lappert, M. F.; Raston, C. L. Chemistry of Organo-
Zirconium and Hafnium Compounds; Ellis Horwood Limited: Chichester,
England, 1986. (b) Buchwald, S. L.; Nielsen, R. B. Chem. ReV. 1988, 88,
1047-1058. (c) Negishi, E.; Takahashi, T. Acc. Chem. Res. 1994, 27, 124-
130. (d) Fagan, P. J.; Nugent, W. A.; Calabrese, J. C. J. Am. Chem. Soc.
1994, 116, 1880-1889.
(13) Due to the oxophilicity of titanium, cleavage of the Ti-O bond in
titanium oxametallacycles to regenerate the titanium catalyst also presents
a notable challenge. For recent examples of catalytic reductive cyclization
of enones using Cp2Ti(PMe3)2, see: (a) Kablaoui, N. M.; Buchwald, S. L.
J. Am. Chem. Soc. 1995, 117, 6785-6786. (b) Crowe, W. E.; Rachita, M.
J. J. Am. Chem. Soc. 1995, 117, 6787-6788.
(14) Integration of the crude reaction mixture was performed using
fluorobenzene as an internal standard. The perfluoronaphthalene was isolated
following chromatography on silica with pentane. The fraction was collected,
and rotatory evaporation yielded 0.665 g (2.44 mmol, 40%) of white
crystalline perfluoronaphthalene.
(7) Harrison, R. G.; Richmond, T. G. J. Am. Chem. Soc. 1993, 115,
5303-5304.
(8) Bennett, B. K.; Harrison, R. G.; Richmond, T. G. J. Am. Chem. Soc.
1994, 116, 11165-11166.
(9) (a) Allmer, K.; Feiring, A. E. Macromolecules 1991, 24, 5487-5488.
(b) Marsella, J. A.; Pez, G. P.; Coughlin, A. M. U.S. Patent 5 026 929,
1991. (c) Marsella, J. A.; Gilicinski, A. G.; Coughlin, A. M.; Pez, G. P. J.
Org. Chem. 1992, 57, 2856-2860.
(10) (a) Weydert, M.; Andersen, R. A.; Bergman, R. G. J. Am. Chem.
Soc. 1993, 115, 8837-8838. (b) Weydert, M.; Andersen, R. A. In Inorganic
Fluorine Chemistry: Toward the 21st Century; Thrasher, J. S., Strauss, S.
H., Eds.; ACS Symposium Series 555; American Chemical Society:
Washington, DC, 1994; pp 383-391.
(11) Burdeniuc, J.; Chupka, W.; Crabtree, R. H. J. Am. Chem. Soc. 1995,
117, 10119-10120.
0002-7863/96/1518-1805$12.00/0 © 1996 American Chemical Society

1806 J. Am. Chem. Soc., Vol. 118, No. 7, 1996
Communications to the Editor
Several additional experiments support the notion that a
nascent low-valent metallocene species is mediating the ob-
served reductive defluorination chemistry. Treatment of 1 with
“Cp2Zr” (generated from 1 equiv of Cp2ZrCl2 and 2 equiv of
n-BuLi) affords 2.16 Independent generation of “Cp2Zr” and
“Cp2Ti” (photochemically via reductive elimination of biphenyl
from Cp2ZrPh2 and Cp2TiPh2, respectively17) in the presence
of 1 similarly affords 2, thus confirming that the low-valent
zirconocene and titanocene reagents are stoichiometrically
competent to carry out intermolecular C-F bond activation of
the saturated perfluorocarbon.
Interestingly, the zirconocene system (Cp2ZrCl2 + Mg/HgCl2)
is also active for the stepwise hydrogenation of aromatic C-F
bonds at room temperature. For instance, a THF solution of
2.9 mmol of perfluorodecalin and 3.5 mmol of Cp2ZrCl2 with
12 mmol of magnesium turnings (3.8 mmol of HgCl2) was
prepared at room temperature, and a 19F NMR spectrum
recorded after 2 h showed that all of the perfluorodecalin (1)
had reacted and that octafluoronaphthalene (2) and 1,3,4,5,6,7,8-
heptafluoronaphthalene (5, identified and quantified by 19F NMR
spectroscopy18 and GC/MS) were the principal organic products
in 55% and 35% yields, respectively. After the solution was
mixed for 14 h at room temperature, the dominant organic
product was 1,3,4,5,7,8-hexafluoronaphthalene (6) (Chart 1).
Deuterium incorporation in 5 and 6 from THF-d8 demonstrates
that the solvent is the proton source. In contrast to the high
temperatures and pressures typically required for C-F hydro-
Chart 1
genation reactions, it is remarkable that these selective hydro-
genations can be performed under such mild conditions.19
This chemistry is not limited to substrates with tertiary C-F
centers. Stirring Cp2ZrCl2 (or Cp2TiCl2) with 5 equiv of
perfluorocyclohexane (7) in the presence of activated magnesium
in THF solution for 24 h affords unreacted perfluorocyclohexane
and 1,2,4,5-tetrafluorobenzene (8) in ∼35% yield based upon
zirconium as determined using 19F NMR spectroscopy20 and
confirmed by comparison with commercial samples (eq 3).
Under identical reaction conditions, hexafluorobenzene also
affords 1,2,4,5-tetrafluorobenzene. The quantitative generation
of pentafluorobenzene is observed prior to the formation of
1,2,4,5-tetrafluorobenzene.21 As above, deuterium incorporation
was observed in THF-d8. Unlike the more reactive substrates
that contain tertiary C-F bonds, perfluorocyclohexane and
hexafluorobenzene do not exhibit any reactivity with activated
magnesium in the absence of metallocene.
The above results suggest that an electron-transfer mechanism
is operative whereby the metallocene fragment serves as an
“electron shuttle” in transferring electrons from the terminal
reductant to organic fluorinated substrates. Burk and co-workers
proposed an electron-transfer mechanism for fluoride abstraction
from tetrakis(trifluoromethyl)cyclopentadienone by a bis(cy-
clopentadienyl)titanacyclobutane complex.22 It is unclear whether
MII or MIII (M ) Ti, Zr) species are involved in this chemistry;
however, reversible III/IV couples are well known for titanocene
and zirconocene complexes.12a Mechanistic studies on these
intriguing transformations are currently in progress.
(15) A 100 mL Schlenk flask was charged with 0.147 g of Cp2ZrCl2
(0.502 mmol), 1.50 g of HgCl2 (5.52 mmol), 1.38 g of magnesium turnings
(56.9 mmol), and 25 mL of freshly distilled THF. The resulting slurry was
degassed, and 1.50 mL of perfluorodecalin (6.19 mmol) was added by
syringe. The reaction mixture was stirred at room temperature for 3 h. The
reaction affords 1.50 mmol of octafluoronaphthalene (30 fluorides removed
per zirconium metal center or three turnovers based on Cp2ZrCl2) as
determined by 19F NMR spectroscopy using added fluorobenzene as an
internal standard.
(16) (a) Negishi, E.; Holmes, S. J.; Tour, J. M.; Miller, J. A.; Cederbaum,
F. E.; Swanson, D, R.; Takahashi, T. J. Am. Chem. Soc. 1989, 111, 3336-
3346. (b) A 100 mL Schlenk flask was charged with 0.548 g of Cp2ZrCl2
(1.87 mmol) and 20 mL of freshly distilled THF. The solution was degassed
and cooled to -70 °C. n-BuLi (6.32 mmol, 2.5 M) was added via syringe,
and the resulting mixture was stirred at -70 °C for 10 min. Perfluorodecalin
(0.060 mL, 0.248 mmol) was then added, and the resulting reaction mixture
was warmed slowly to room temperature with stirring under nitrogen over
a period of 11 h. The reaction afforded 0.124 mmol of octafluoronaphthalene
(50% conversion based on C10F18) as determined by 19F NMR spectroscopy.
A control experiment showed that there is no reaction between n-BuLi and
perfluorodecalin.
Acknowledgment. The authors thank Boulder Scientific for their
support of our exploratory research in the form of a generous donation
of metallocenes. An AAUW American Fellowship to J.L.K. is
gratefully acknowledged (1995-1996). The mass spectrometer was
purchased with funds from the NSF (CHE-9002690) and the University
of Utah Institutional Funds Committee. This research was supported
in part by the Alfred P. Sloan Foundation through a Research Fellowship
awarded to T.G.R. (1991-1995).
(17) (a) Alt, H.; Rausch, M. D. J. Am. Chem. Soc. 1974, 96, 5936-
5937. (b) Rausch, M. D.; Boon, W. H.; Mintz, E. A. J. Organomet. Chem.
1978, 160, 81-92.
(18) Bolton, R.; Sandall, J. P. B. J. Chem. Soc., Perkin Trans. 2 1978,
746-750.
(19) Hudlicky, M. Chemistry of Organic Fluorine Compounds, 2nd ed.;
Wiley: New York, 1976; pp 174-178.
(20) A 100 mL Schlenk flask was charged with 0.0795 g of Cp2ZrCl2
(0.272 mmol), 0.0887 g of HgCl2 (0.327 mmol), 1.35 g of magnesium
turnings (55.6 mmol), and 10 mL of freshly distilled THF. Perfluorocy-
clohexane (0.475 g, 1.58 mmol) was added, and the resulting mixture was
degassed and allowed to stir at room temperature. After 24 h, the resulting
yellow solution consists of primarily tetrafluorobenzene and unreacted
perfluorocyclohexane. The reaction affords 0.0962 mmol of tetrafluoroben-
zene (35.4% based on Cp2ZrCl2) as determined by 19F NMR spectroscopy
using added fluorobenzene as an internal standard.
Supporting Information Available: Complete experimental pro-
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(21) Dungan, C. H.; van Wazer, J. R. Compilation of Reported 19F NMR
Chemical Shifts; Wiley: New York, 1970.
(22) Burk, M. J.; Staley, D. L.; Tumas, W. J. Chem. Soc., Chem.
Commun. 1990, 809-810.
JA952563U