Proton-catalyzed, silane-fueled friedel-crafts coupling of fluoroarenes

Article abstract of DOI:10.1126/science.1202432

The venerable Friedel-Crafts reaction appends alkyl or acyl groups to aromatic rings through alkyl or acyl cation equivalents typically generated by Lewis acids. We show that phenyl cation. Friedel-Crafts reaction to intramolecular aryl couplings. The enabling feature of this reaction is the exchange of carbon-fluorine for silicon-fluorine bond enthalpies; the reaction is activated by an intermediate silyl cation. Catalytic quantities of protons or silyl cations paired with weakly coordinating carborane counterions initiate the reactions, after which proton transfer in the final aromatization step regenerates the active silyl cation species by protodesilylation of a quaternary silane. The methodology allows the high-yield formation of a range of tailored polycyclic aromatic hydrocarbons and graphene fragments.

Full text of DOI:10.1126/science.1202432

REPORTS
ly useful aryl-aryl couplings typically involve an
activated nucleophilic aryl partner, an aryl bromide
or iodide, and a transition metal catalyst (8–10).
Omission of the transition metal, selection of an
aryl fluoride, and use of an unactivated aryl nu-
cleophile are not contemplated by any reactive
scheme currently in the chemist’s repertoire (11, 12).
Proton-Catalyzed, Silane-Fueled
Friedel-Crafts Coupling of Fluoroarenes
Oliver Allemann, Simon Duttwyler, Paola Romanato, Kim K. Baldridge, Jay S. Siegel*
The venerable Friedel-Crafts reaction appends alkyl or acyl groups to aromatic rings through alkyl Therefore, the efficient intramolecular coupling
or acyl cation equivalents typically generated by Lewis acids. We show that phenyl cation
equivalents, generated from otherwise unreactive aryl fluorides, allow extension of the
Friedel-Crafts reaction to intramolecular aryl couplings. The enabling feature of this reaction is
of an arene with an aryl fluoride by carbon-fluoride
bond activation constitutes an avenue of synthet-
ically useful Friedel-Crafts reactivity ripe for
the exchange of carbon-fluorine for silicon-fluorine bond enthalpies; the reaction is activated by an exploration.
intermediate silyl cation. Catalytic quantities of protons or silyl cations paired with weakly
coordinating carborane counterions initiate the reactions, after which proton transfer in the
final aromatization step regenerates the active silyl cation species by protodesilylation of a
quaternary silane. The methodology allows the high-yield formation of a range of tailored polycyclic
aromatic hydrocarbons and graphene fragments.
Carbon-fluorine bond activation by silyl cations
has been applied to assist hydrodefluorination of
benzyl and alkyl fluorides (13, 14). In addition,
silyl cations are instrumental in supporting ali-
phatic carbon-carbon bond formation (15). The
mechanism is ascribed to the formation of well-
ormation of carbon-carbon bonds via Friedel- pertain to many organometallic transformations known alkyl cation equivalents, which can be trapped
Crafts methodology is one of synthetic (4). With respect to aryl-aryl couplings, Friedel- in classical Friedel-Crafts reactions. In contrast,
organic chemistry’s charter reactions, in- Crafts chemistry is limited by the thermodynamic
F
volving the attack by electron-rich p-clouds of instability of the phenyl cation (5); however, the
aromatic rings onto carbocation-like substrates importance of such couplings has mothered the
(1, 2). This reaction is of fundamental importance invention of a plethora of noble and coinage
Organic Chemistry Institute, University of Zürich, Winterthurerstrasse
190, Zürich CH-8057, Switzerland.
*To whom correspondence should be addressed. E-mail:
to industry (3), and its mechanistic principles also metal–mediated methodologies (6, 7). These high- jss@oci.unizh.ch
was purified by flash column chromatography. The conversion was measured
by GC-MS; the isolated yields are reported only for conditions that led to
complete conversion. Mes = 2,4,6-trimethylbenzene.
Table 1. Conditions for C–F activation applied on 1-(2-fluorophenyl)
naphthalene. Reactions were all conducted with 0.1 mmol of 1-(2-
fluorophenyl)naphthalene under permanent inert atmosphere. The product
Time Conv. Yield
#
Cation
Anion
Base*
P(o-tol)3
Solv.
T (°C)
(h)
(%)
(%)
iPr3Si+
iPr3Si+
i Pr3Si+
1
2
[CB11H6Cl6]–
[CB11H6Cl6]–
[CB11H6Cl6]–
[B(C6F5)4]–
PhMe
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
80
110
110
110
110
110
110
25
18
15
8
<10
100
100
60
–
80
90
–
P(o-tol)3
2,6-di-tBu-pyridine
Me2Si(Mes)2
Me2Si(Mes)2
Me2Si(Mes)2
Me2Si(Mes)2
Me2Si(Mes)2
Me2Si(Mes)2
Me2Si(Mes)2
3
Ph3C+/iPr3SiH
iPr3Si+ †
4
16
8
5
[CB11H6Cl6]–
[CB11H6Cl6]–
[CB11H6Cl6]–
[CB11H6Cl6]–
[CB11H6Cl6]–
[CB11H6Cl6]–
100
100
100
<10
100
100
93
90
86
–
iPr3Si+ ‡
6
17
8
Ph3C+/iPr3SiH†
Ph3C+/Me2(Mes)SiH†
Ph3C+/Me2(Mes)SiH†
Mesitylene–H+ †
7
8
15
8
9
110
110
89
92
10
8
*Entries 1–3 use an explicit base to neutralize the proton generated; entries 4–10 couple neutralization to the
generation of the next silyl cation through a protodesilylation. †10 mol-%. ‡4 mol-%.
574
29 APRIL 2011 VOL 332 SCIENCE www.sciencemag.org

REPORTS
aryl carbon-fluorine bonds appeared sufficiently like species. Indeed, addition of triisopropylsilyl Overall, the exchange of covalent bonds [C(ar)–H,
inert in these studies such that aryl-fluorides could carborane (1) (19, 20) to a substrate such as 1-(2- C(ar)–C(ar), and Si–F for C–(ar)–H, Si–C(ar),
be used as solvents without interference; forma- fluorophenyl)naphthalene (2) effects the activa- and C(ar)–F] is thermodynamically highly favor-
tion of phenyl cation was not anticipated (13, 14). tion of the carbon-fluorine bond and formation of able. Thus, an elegant self-sustaining reaction sys-
The driving force for the reaction comes from a new arene-arene bond, leading to the product tem comprises the arene or aryl fluoride (as substrate)
the substantial Si–F bond strength relative to that fluoranthene (3).
and an arylsilane (as fuel that consumes protons
of the C(aliphatic)–F bond. Notably, the strength An equivalent of one proton is generated dur- and releases silyl cations), plus a substoichiometric
of the Si–F bond exceeds even that of the C(aryl)– ing the reaction; the neutralization of this charge amount of a silyl cation (as initiator).
F bond by about 120 kJ mol–1 (16, 17), and fluo- by a sterically hindered Brønsted base prevents
Substoichiometric use of the preformed silyl
ride abstraction from fluoroarenes by silyl Lewis undesired polymerization reactions. A moment’s cation species described above only provides a
acids was recently demonstrated (18). Given these reflection reveals that this proton need not be shunt into this reaction manifold. The proton
findings, a silylium-promoted Friedel-Crafts aryl- simply scavenged, but rather can be channeled generated during the reaction (for example, as
ation appears feasible in terms of bond enthalpies into a productive part of the reaction. Protodesilyl- [fluoranthene-H]+[carborane]–) is the actual cata-
and reaction kinetics.
ation of arylsilanes to yield an equivalent of a lyst. Arenium carboranes—protonated arenes paired
In a brute-force approach, one would com- silylium ion and an arene is a well-known phe- with carborane counterions—are a young class of
bine the organic substrates with a stoichiometric nomenon relying on the greater bond enthalpies of superacids that can be isolated in pure form (24).
amount of a silyl cation to effect fluoride abstrac- C–H bonds over those of Si–C bonds (21–23). Thus, direct addition of an arenium carborane, in-
tion, and a Brønsted base to neutralize the Wheland Given that the silyl cation–initiated Friedel-Crafts stead of the silylium initiator, should effect a reaction
intermediate (B, Fig. 1), which arises from attack arylation formally generates one equivalent of HF, wherein a proton serves as the catalyst to transform
by the nucleophilic arene on the incipient aryl cat- the proton formed after the first C(aryl)–C(aryl) a neutral silane into an intermediate silyl cation.
ion. This strategy necessitates the availability of a coupling can serve as a catalyst to generate a silyl This cation then activates the carbon-fluorine bond,
full equivalent of a sufficiently reactive silylium- cationic species from a neutral silane precursor. thereby inducing arene-arene coupling and release
of a proton to recommence the process.
The substrate 1-(2-fluorophenyl)naphthalene
(2) served as a model substrate for developing
suitable Friedel-Crafts reaction conditions. Upon
activation of the C–F bond, 2 undergoes ring clo-
sure to furnish fluoranthene (3). Initially, condi-
Table 2. C–F activation reaction on various substrates; conditions from entry 5 of Table 1 were used for
these transformations.
Educt
Product
Yield (%)
tions involving stoichiometric amounts of silyl
cation and a sterically hindered Brønsted base
were investigated (25). Performing the reaction
with iPr3Si–CB11H6Cl6 and either P(o-tol)3 or
2,6-di-tert-butylpyridine at 110°C for 8 to 15 hours
led to high conversions and isolated yields of
3 (Table 1). Chlorobenzene proved to be a suit-
able solvent for this transformation and afforded
better results than toluene. The more Lewis-basic
toluene may deactivate the silylium carborane by
p coordination (26). Intermolecular aryl-aryl cou-
pling between toluene and the incipient phenyl
cation was not observed.
The ring closure also proceeded effectively
with substoichiometric silyl cation as initiator
in combination with a stoichiometric amount
of silane. This approach led to isolated yields
of up to 93% using iPr3Si–CB11H6Cl6 (1) and
Me2SiMes2 (4). It is possible to carry out the
reaction either with preformed or in situ gener-
ated cations (Table 1), the former giving slightly
better yields. An attempt to run the reaction at
room temperature yielded only small quantities
of product.
0*
6
7
R1=H, R2=H
R1=Me, R2=H
R1=H, R2=Me
R1=R2=R2'=H
97
99
8
9
R1=Me, R2=R2'=H
R1=R2'=H, R2=Me
R1=R2=H, R2'=Me
R1=R2=Me, R2'=H
R1=R2'=Me, R2=H
10a
10b‡
11a
11a
11b
13a
13b
99
98
R1=R2=Me
12‡
14
15
49
Triggering the reaction with mesitylenium
carborane (5) (a very strong Brønsted acid) resulted
in complete consumption of starting material and
high isolated yield of product. Triisopropylsilylium
(1) and mesitylenium ion (5) act as initiators of
the catalytic cycle (Fig. 1). They start the cat-
alytic cycle at a different state (B and C) but
eventually lead to the same active species, the
mesityldimethylsilyl cation (D).
79
16
18
17
19
51†
Counterions play a significant role in reactive
cation chemistry; chemical stability and low
nucleophilicity are preferred characteristics for
clean cation reactivity. Two classes of anions,
*Starting material recovered. †Partial product decomposition.‡Substrates 10b and 12 form
a mixture of products (11a/11b and 13a/13b) in a ratio of 3:2 (a:b).
www.sciencemag.org SCIENCE VOL 332 29 APRIL 2011
575

REPORTS
Fig. 1. Suggested catalytic
cycle of the fluoride abstrac-
tion and the subsequent in-
tramolecular attack, using the
example of transformation of
1-(2-fluorophenyl)naphtha-
lene to fluoranthene.
F
F
Si
Si
F
starting
material (2)
A
iPr3Si+ (1)
F
Si+
H
–iPr3SiF
initiation 1
D
B
Si
Si
H
C
[Mesitylene–H]+ (5)
–Mesitylene
initiation 2
product formation
product (3)
silylium regeneration
Si
(4)
Fig. 2. MP2/DZ(2df,pd)//
B98/DZ(2df,pd) calcu-
lated transition state
(TS), including effects of
chlorobenzene solvent,
for fluoride abstraction
from 1-(2-fluorophenyl)-
naphthalene (calculated
enough to protonate the electron-rich mesityl ring
of dimethyldimesitylsilane. Elimination of me-
sitylene reforms the silyl cation (D) and com-
pletes the catalytic cycle.
An early assessment of the scope of the re-
action shows its applicability to the synthesis of a
variety of polynuclear aromatic hydrocarbons
(Table 2). It is effective in couplings involving
fullerene fragments and could be an alternative
to Scholl chemistry toward the formation of graphene
and other carbon-based mesogens (32, 33). Re-
ductive activation of carbon-halogen bonds, other
than fluorine, has been used toward this goal of
forming graphene subunits, but often steric crowd-
ing prohibits the formation of the necessary pre-
cursors. The small steric profile of the fluorine
atom and the need to have only one derivatized
partner adds substantial value to this methodol-
ogy for preparing tailored graphene models.
For the formation of less strained five- or
six-membered ring systems, conditions were
Ea = 19.8 kcal mol–1
;
transition-state inter-
atomic lengths, C–F =
2.55 Å, C–C = 2.86 Å).
perfluorinated tetraphenylborates and carboranes component of the acid-catalyzed reaction mecha- adapted to obtain yields between 49 and 99%.
(27, 28), are very weakly coordinating anions nism, and heating is necessary for the product to In contrast, it has not yet been possible to gen-
with widely distributed negative charge (29). In form within an adequate period of time.
erate the four-membered ring of biphenylene
It is likely that C–F activation does not take (7) from substrate 6 by applying this method.
the present case, the carborane [CHB11H5Cl6]–
afforded superior results to those with [B(C6F5)4]–, place by a completely dissociative mechanism, Terphenyl educts 8, 10a, 10b, and 12 showed
consistent with earlier reports showing a higher because C6H4R+ would have a very unfavorable full conversion to products 9, 11a, 11b, 13a,
robustness of carboranes toward high temperature electronic configuration (31). Irrespective of the and 13b using optimized conditions (Table 1,
and Brønsted acidity relative to the perfluorinated mechanistic details, after ring closure, the result- entry 5). The yields were between 97 and 99%.
phenylborates (24, 30). High acidity is an inherent ant protonated aryl moiety B is evidently acidic Substrates 14 and 16 were more difficult to
576
29 APRIL 2011 VOL 332 SCIENCE www.sciencemag.org

REPORTS
15. N. Lühmann, R. Panisch, T. Müller, Appl. Organomet.
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Additional silylium carborane and silane, plus arene accelerates the reaction.
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(2003).
extra hours of stirring, were required to achieve
The proton is likely the universe’s oldest cata-
a higher yield. Treatment of substrate 18 afforded lyst, and it is now available as a crystalline arenium
a yield of 51%; the lower yield was probably carborane (25). Coupled to a neutral silane as fuel,
17. Y.-R. Luo, Comprehensive Handbook of Chemical Bond
Energies (CRC Press, Boca Raton, FL, 2007).
18. S. Duttwyler et al., Angew. Chem. Int. Ed. 49, 7519
(2010).
caused by decomposition of the product (19).
arenium acids are competent catalysts for the long-
The terphenyl substrates containing a methyl sought phenyl cation–based Friedel-Crafts reac-
group on the nonfluorinated phenyl ring (10b and tivity. Such C–F activation for the formation of
12) showed a mixture of ortho and para products. arene-arene bonds complements transition metal–
The distribution was slightly in favor of the para based arene-arene couplings, particularly for the
position, which should be more accessible; how- formation of designed graphenes and higher-order
ever, the small preference for the para methyl in- polynuclear aromatic hydrocarbon–based mate-
dicates a very reactive intermediate that does not rials. Understanding the science of silyl cations
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distinguish strongly between the two positions.
and phenyl cation–like intermediates at play here,
Additional studies enabled us to make a along with the design of tailored precursors, will
qualitative statement on the reaction rate. The certainly lead to a useful expansion of the syn-
terphenyl substrates (8, 10a, 10b, and 12) were thetic chemist’s tool box and the material chem-
used in competitive C–F activation reactions. ist’s objects of investigation.
Two substrates were added to the same reaction
mixture with only half an equivalent of reagent.
Gas chromatography–mass spectrometry (GC-
MS) consistently showed that substrates con-
taining methyl groups (at any of the two rings)
reacted faster than did the electron-poorer rings
without substituents. The tendency of reaction
rates for different substrates was found to be 8 >
10a ≈ 10b > 12 (25). This observation matches
with the proposed transition state A. Its positive
charge would be stabilized by an increased elec-
tron density of the fluorophenyl ring, provided by
an additional substituent such as the methyl group.
Methylation of the donor arene had the same ef-
fect on the reaction rate.
For the transformation of substrate 2, quan-
tum mechanical calculations predicted a transi-
tion state for the fluoride abstraction (Fig. 2) that
nearby aryl moieties can stabilize (18, 25). The
structural and activation parameters predicted
by the quantum chemical model (calculated Ea =
19.8 kcal mol–1; transition-state interatomic lengths,
C–F = 2.55 Å, C–C = 2.86 Å) fit well with the
experimental findings (34). The model further
References and Notes
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11. The action of SbF5 on perfluorinated naphthalene forms
radical cations capable of coupling with pentafluorinated
benzene, albeit with limited substrate scope; see (35).
12. Flash vacuum pyrolysis appears to facilitate the lysis of
C(aryl)–F bonds and thereby promote arene-arene
coupling; see (36).
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34. Specific coordination of solvent or counterion is
estimated to have an effect of <5 kcal/mol on activation
parameters, such that the model is still consistent with
a reaction at 80°C over several hours.
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Acknowledgments: We thank the Swiss National Science
Foundation for financial support.
Supporting Online Material
www.sciencemag.org/cgi/content/full/332/6029/574/DC1
Materials and Methods
Table S1
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3 January 2011; accepted 16 March 2011
10.1126/science.1202432
veals upper cloud features at ~70 to 75 km
altitude (11), thermal infrared observations reveal
cloud structures at slightly lower altitudes of 65
to 70 km and show that the center of the southern
polar vortex has a brightness temperature ~15 K
warmer than a surrounding cold collar (15). The
mean cloud-top altitude is close to 74 km up to
mid-latitudes in both hemispheres but decreases
Venus’s Southern Polar Vortex
Reveals Precessing Circulation
D. Luz,1* D. L. Berry,2 G. Piccioni,3 P. Drossart,4 R. Politi,3 C. F. Wilson,5 S. Erard,4 F. Nuccilli6
Initial images of Venus’s south pole by the Venus Express mission have shown the presence of a
bright, highly variable vortex, similar to that at the planet’s north pole. Using high-resolution infrared
measurements of polar winds from the Venus Express Visible and Infrared Thermal Imaging
Spectrometer (VIRTIS) instrument, we show the vortex to have a constantly varying internal structure,
with a center of rotation displaced from the geographic south pole by ~3 degrees of latitude and that
drifts around the pole with a period of 5 to 10 Earth days. This is indicative of a nonsymmetric and
varying precession of the polar atmospheric circulation with respect to the planetary axis.
1Centro de Astronomia e Astrofísica da Universidade de Lisboa,
Observatório Astronómico de Lisboa, 1349-018 Lisboa, Portugal.
2Departamento de Física, Universidade de Évora, 7002-554
Évora, Portugal. 3Istituto Nazionale di Astrofisica, Istituto
Nazionale di Astrofisica– Istituto di Astrofisica Spaziale e
Fisica Cosmica (INAF-IASF) Rome, 00133 Rome, Italy. 4Labo-
ratoire d’Études Spatiales et d’Instrumentation en Astrophysique,
Observatoire de Paris, CNRS, Université Pierre et Marie Curie,
Université Paris-Diderot, F-92195 Meudon Cedex, France.
5Department of Physics, University of Oxford, Oxford OX1 3PU,
UK. 6INAF–Istituto di Fisica dello Spazio Interplanetario (IFSI)
Rome, 00133 Rome, Italy.
enus has the most extreme atmospheric polar regions in hemispheric spiral-like patterns
circulation of the terrestrial planets, with of clouds (11), where it results in fast rotating,
V
the cloud-level atmosphere spinning on infrared-bright central vortices (12–15).
average 60 times faster than the planet’s surface Although the spiral hemispheric patterns can
*To whom correspondence should be addressed. E-mail:
(1). This superrotation (2–10) extends to both be seen in ultraviolet dayside imagery, which re- dluz@oal.ul.pt
www.sciencemag.org SCIENCE VOL 332 29 APRIL 2011
577