Intramolecular aryl-aryl coupling of fluoroarenes through Al 2O3-mediated HF elimination

Article abstract of DOI:10.1021/jo300783y

A strategy for effective intramolecular aryl-aryl coupling of fluoroarenes through Al₂O₃-mediated HF elimination is reported. It is demonstrated that the C-F bond, which is widely believed to be the most passive functionality in organic chemistry, can be reconsidered as a useful functional group allowing very effective C-C bond formation. The solid-state strategy presented in this study opens the possibility for facile syntheses of insoluble extended polycyclic aromatic hydrocarbons.

Full text of DOI:10.1021/jo300783y

Note
pubs.acs.org/joc
Intramolecular Aryl−Aryl Coupling of Fluoroarenes
through Al2O3-Mediated HF Elimination
K.Yu. Amsharov* and P. Merz
Max Planck Institute for Solid State Research, Heisenbergstrasse 1, 70569 Stuttgart, Germany
S
* Supporting Information
ABSTRACT: A strategy for effective intramolecular aryl−aryl coupling of
fluoroarenes through Al2O3-mediated HF elimination is reported. It is
demonstrated that the C−F bond, which is widely believed to be the most
passive functionality in organic chemistry, can be reconsidered as a useful
functional group allowing very effective C−C bond formation. The solid-
state strategy presented in this study opens the possibility for facile
syntheses of insoluble extended polycyclic aromatic hydrocarbons.
he carbon−fluorine bond is one of the least reactive
small arenes where four-, five-, and six-membered rings can
be formed by intramolecular aryl−aryl coupling were chosen as
model compounds (Figure 1). The condensations of the
respective fluoroarenes were carried out at 100−250 °C using
thermally activated γ-Al2O3. The reaction products were
extracted with toluene and subsequently analyzed.
T
functionalities encountered in chemistry, and its selective
transformation leading to C−C bond formation is a major
challenge in modern organic chemistry.1 C−F activation in the
coordination sphere of a transition metal is the most commonly
used approach.2 Despite significant progress in this field, only a
few examples of effective aryl−aryl coupling using aryl fluorides
have been reported so far.1−3 Moreover, in the case of transition-
metal-catalyzed C−F activation, moderate yields have been
achieved only for electronically activated aryl fluorides and/or in
the presence of directing groups. Rather selective intramolecular
fluorine-promoted aryl−aryl coupling has been observed under
flash vacuum pyrolysis condition.4,5 The main drawbacks in this
case are minimum functional group tolerance as a consequence
of the harsh reaction conditions required and difficulties in scale
up. Alternatively, the C−F bond can be effectively activated
under transition-metal-free conditions utilizing silylium−carbor-
ane catalysis.6 Recently, this methodology has been successfully
applied for intramolecular aryl−aryl coupling.7 Unfortunately, the
use of an exotic and expensive carborane cluster limits the
application of the approach at the preparative scale. Recently, we
have demonstrated that intramolecular aryl−aryl coupling in the
cove region of 1-fluorobenzo[c]phenanthrene (compound 1)
and several structurally related compounds can be realized very
effectively through HF elimination on thermally activated γ-
Al2O3.8 Under these conditions, the conversion to the target
molecules has been achieved quantitatively, even in the case of
multifold condensations. The process discovered is characterized
by an unprecedentedly high chemoselectivity and regiospecificity.
Simplicity, high efficiency, and easy availability of aluminum
oxide make the reaction very attractive as a general synthetic
strategy. In this paper, we report that the scope of condensation
via Al2O3-mediated HF elimination can be extended to the
synthesis of various polycyclic aromatic hydrocarbons (PAHs),
thus providing a new general approach for effective intra-
molecular aryl−aryl coupling.
As expected, fluorobiphenyl 3 has remained completely intact
under condensation conditions. Neither condensation nor C−F
bond cleavage was observed, demonstrating that the C−F bond
remains completely inert if no appropriate position for coupling
is offered by the structure. In contrast, the phenylnaphthalene 5
readily undergoes transformation to fluoranthene (6) already at
100 °C. In comparison to benzophenanthrene 1, the condensation
of 5 requires a longer time. While 1 can be condensed quan-
titatively to 2 at 200 °C after several minutes, 5 gave low
conversion to 6 under the same conditions. Moreover, it was
found that the condensation process is extremely sensitive to
the pretreatment activation of Al2O3. Thus, only trace amounts
of fluoranthene formed if nonactivated Al2O3 was used, and
only low conversion to the target compound was observed with
aluminum oxide activated at 300 °C. The effective con-
densation of 5 to 6 can be achieved only after proper activa-
tion of Al2O3 at 600 °C (for details, see the Supporting
Information). When such an activated Al2O3 was used, the full
conversion was achieved after 10 h at 200 °C. In this case, the
target fluoranthene was obtained in pure form after simple
extraction with toluene as indicated by HPLC and NMR
analysis. Although almost no side products were detected in the
toluene extract, the isolated yield of fluoranthene was found to
be only 60%. This indicates that about 40% of 5 react with
aluminum oxide forming nonextractable products.9 Fortunately,
the side processes can be effectively suppressed at lower
temperatures. Thus, the condensation of 5 at 150 °C for 60 h
gave fluoranthene with more than 80% yield.
2-Fluorobiphenyl (3), 1-(2-fluorophenyl)naphthalene (5),
and 1-(2-fluorophenyl)-2-phenylbenzene (7) representing
Received: April 26, 2012
Published: May 24, 2012
© 2012 American Chemical Society
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Figure 2. Double aryl−aryl coupling via Al2O3-mediated HF
elimination.
SiO2, Sc2O3, TiO2, ZnO, Ga2O3, GeO2, ZrO2, SnO, Nb2O5,
In2O3, and HfO2) only Al2O3 has shown high activity in
condensation.11
Considering the proposed mechanism of condensation the
molecule should be in close contact to an active site of aluminum
oxide in order to undergo elimination. In the cases of small
fluoroarenes which melt below the temperatures used for
condensation, there are obviously no obstacles for free diffusion.
Interestingly, when both starting materials and products have
remarkably higher melting points than the temperature of the
reaction the elimination can also be realized very effectively,
demonstrating sufficient mobility of the reacting molecules.8 Such
a behavior is understandable since diffusion and therefore the
reaction between two solids frequently begins far below the
melting point (Tammann temperature). Nevertheless, in the case
of extra-large PAHs, a decrease in activity cannot be excluded. On
the other hand, the problem of mobility can be solved by using an
appropriate solvent. It has been found that the reaction proceeds
with the same efficiency in refluxing dodecane, 1,2,4-trichlor-
obenzene, and naphthalene.12 The use of polar solvents such as
dimethylacetamide completely inhibits the process, probably due
to blocking of active sites on the Al2O3 surface. The possibility of
carrying out the process in trichlorobenzene additionally
demonstrates a high tolerance to the CAryl-Cl functionality,13
whereas an effective condensation in naphthalene, which
represents an excellent scavenger of carbocations, rules out the
possibility of condensation via carbocation intermediates.
Figure 1. Aryl−aryl coupling via Al2O3-mediated HF elimination.
In contrast to pentagon formation, the closure of the six-
membered ring in diphenylbenzene 7 proceeds very smoothly.
Rather effective condensation of 7 to triphenylene (8) can be
achieved already at 100 °C after 10 h. At 200 °C, the same
process can be completed in several minutes with quantitative
formation of triphenylene (isolated yield 99.5%).
Despite the moderate yield in the case of pentagon closure,
the approach is rather efficient since the product obtained
requires no further purification. The efficiency has been
demonstrated on the example of double HF elimination in
diphenylnaphthalene 9 (Figure 2). Annealing at 200 °C for 60 h
gave compound 10 in pure form with 34% yield (see the
Supporting Information). The efficiency of hexagon closure has
been demonstrated on the example of double HF elimination in
compound 11. Quinquephenyl 11 was quantitatively trans-
formed to phenanthrotriphenylene 12 at 150 °C after 120 h. The
product was obtained in pure form after Soxhlet extraction with
toluene.
The most probable mechanism of condensation includes
aromatic transition states which explains the high selectivity and
low activation barrier allowing the reaction to take place under
rather mild conditions.8 As previously observed, Al2O3
mediated 1,2-dehydrofluorination in difluorocycloalkanes has
probably a similar mechanism of elimination as evidenced by
highly selective fluorocycloalkenes formation.10 The driving
force of the elimination is the formation of an Al−F bond
which is characterized by substantial bond strength. Indeed, it
has been found that Al2O3 plays a crucial role in the reaction.
Thus, among several oxides tested (BeO, B2O3, MgO, Al2O3,
In summary, a facile solid-state strategy for effective aryl−aryl
coupling by Al2O3-mediated HF elimination is presented. Our
finding shows that the C−F bond is a useful functional group
allowing effective C−C bond formation. The efficiency of the
approach has been shown by the syntheses of several PAH
structures. Importantly, the desired products can be obtained in
pure form after simple extraction, and no additional purification
procedures are required (see the Supporting Information). It
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Note
times with 100 mL of water. The organic layer was dried over sodium
sulfate, and the solvent was removed under reduced pressure. The 11
was purified by flash chromatography on silica gel using CCl4 as eluent.
After evaporation, the product was obtained as a white solid (0.81 g,
was also demonstrated that the C−F bond remains intact if no
possibility for cyclization is offered. Such a regiospecifity, which
is without precedent in fluoroorganic chemistry, offers the
possibility for condensations in a domino-like fashion. More-
over, the high tolerance to chlorine and bromine function-
alities13 makes the approach a very powerful synthetic tool for
the synthesis of halogenated PAHs, which are useful building
blocks for the construction of more complex structures. The
exceptionally high conversion level for hexagon closure and the
applicability to insoluble materials open new horizons for
construction of extra-large PAHs via multifold intramolecular
cyclization. In particular, the approach is of great interest for
the rational synthesis of carbon-based nanostructures, including
fullerenes,14,15 nanotubes,16 nanographenes, and nanorib-
bons.17
1
81% yield): Rf (CCl4) = 0.45; mp 182.0 °C; H NMR (300 MHz,
CD2Cl2) δ 7.46−7.27 (m, 8H), 7.25−7.15 (m, 6H), 7.13−7.04 (m, 4H),
6.68 (t, J = 7.9 Hz, 2H); 13C NMR (75 MHz, CD2Cl2) δ 155.3 (dd, J =
243.8, 3.7 Hz), 141.9 (s), 141.2 (s), 133.4 (s), 131.0 (s), 130.4 (s), 129.8
(dd, J = 14.6, 12.2 Hz), 129.3 (s), 128.8 (s), 128.2 (s), 127.5 (s), 127.1
(s), 118.8−118.1 (m); HRMS (ESI-TOF) m/z = [M]+ calcd for
C30H20F2 418.1533, found 418.1538.
Fluoranthene (6). Fluoranthene was synthesized from 5 (202 mg)
according to the general procedure using 5 g of activated Al2O3. The
condensation was carried out at 150 °C for 60 h. Extraction with
toluene and subsequent evaporation gave pure 6 as white crystals (146
mg, 79% yield). Spectroscopic data were found to be in agreement
with those previously reported.18
Triphenylene (8). Triphenylene was synthesized from 7 (111 mg)
according to the general procedure using 5 g of activated Al2O3. The
condensation was carried out at 250 °C for 10 min. Extraction with
Soxhlet (toluene) and subsequent evaporation gave pure 8 as white
crystals (104 mg, quantitatively). Spectroscopic data were found to be
in agreement with those previously reported.18
Indeno[1,2,3-cd]fluoranthene (10). Compound 10 was synthesized
from 9 (172 mg) according to the general procedure using 5 g of
activated Al2O3. The condensation was carried out at 200 °C for 60 h.
Extraction with toluene and subsequent evaporation gave pure 10 as
orange crystals (51 mg, 34% yield). Spectroscopic data were found to
be in agreement with those previously reported.18
Phenanthro[9,10-b]triphenylene (12). Compound 12 was synthe-
sized from 11 (130 mg) according to the general procedure using 5 g
of activated Al2O3. The condensation was carried out at 150 °C for
120 h. Extraction with Soxhlet (toluene, 3 days) and subsequent
evaporation gave pure 10 as white crystals (114 mg, 97%; additional
extraction with boiling xylene and subsequent HPLC analysis showed
that the product was extracted not completely). Spectroscopic data
were found to be in agreement with those previously reported.19
EXPERIMENTAL SECTION
■
NMR spectra were measured at 20 °C. Rf were determined on TLC-
PET sheets coated with silica gel with fluorescent indicator 254 nm
(layer thickness 0.25 mm, medium pore diameter 60 Å). HPLC
analyses were carried out using a Cosmosil 5-PYE (4.6 mm × 250 mm)
column and toluene/methanol mixture as eluent (UV−vis detection).
Chromatographic purifications were carried out with flash grade silica
gel Kieselgel 60 (0.06−0.2 mm). HF elimination experiments were
carried out using commercially available aluminum oxide (activated,
neutral, 50−200 μm). The aluminum oxides obtained from different
suppliers have shown similar activity in the condensation (see the
Supporting Information). 1-(2-Fluorophenyl)naphthalene (5) and 1-
(2-fluorophenyl)-2-phenylbenzene (7) were synthesized according to
the previously reported procedure.7
General Procedure for Al2O3-Mediated HF Elimination.
Typically, 5 g of γ-Al2O3 was placed in a glass ampule and activated
by annealing under vacuum (10−3 mbar). The temperature was
increased gradually and kept for 15 min at 600 °C. After the mixture
was cooled to room temperature, the ampule was filled with argon.
The respective fluoroarene (50−100 mg) was carefully mixed with
activated aluminum oxide. The ampule was evacuated again and sealed.
The condensation was carried out without stirring at 100−250 °C.
The respective condensation products were obtained after extraction
with toluene and subsequent solvent evaporation.
ASSOCIATED CONTENT
■
S
* Supporting Information
HPLC chromatograms and UV−vis spectra of the condensation
products and 1H and 13C NMR spectra for new compounds. This
material is available free of charge via the Internet at http://pubs.
acs.org.
1,4-Bis(2-fluorophenyl)naphthalene(9). A 1.0 g portion of 1,4-
dibromonaphthalene (3.5 mmol), 1.0 g of 2-fluorobenzeneboronic
acid (7.15 mmol), 4.7 g of Cs2CO3 (14.3 mmol), and 416 mg of
Pd(PPh3)4 (0.36 mmol) were added to the mixture of 30 mL of
toluene and 15 mL of methanol. The reaction mixture was degassed
under dynamic vacuum and stirred for 12 h at 110 °C under argon
atmosphere. After the mixture was cooled to room temperature,
250 mL of diethyl ether was added, and the resulting mixture was
washed three times with 100 mL of water. The organic layer was dried
over sodium sulfate, and the solvent was removed under reduced
pressure. Compound 9 was purified by filtration through silica gel using
petroleum ether/dichloromethane mixture (1:1). After evaporation, the
product was obtained as a white solid (0.79 g, 71% yield): Rf (CCl4) =
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: k.amsharov@fkf.mpg.de.
Notes
The authors declare no competing financial interest.
REFERENCES
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