A catalytic C-C bond-forming reaction between aliphatic fluorohydrocarbons and arylsilanes

Article abstract of DOI:10.1002/aoc.1658

C-C coupling reactions between arylsilanes and alkylfluorides are efficiently catalyzed by disilyl cation 1. Primary as well as secondary alkylfluorides were quantitatively coupled with arylsilanes; however, in the case of tertiary fluorides, the hydrodef

Full text of DOI:10.1002/aoc.1658

Full Paper
Received: 23 February 2010
Revised: 19 March 2010
Accepted: 19 March 2010
Published online in Wiley Interscience: 30 April 2010
(www.interscience.com) DOI 10.1002/aoc.1658
A catalytic C–C bond-forming reaction
between aliphatic fluorohydrocarbons
and arylsilanes
Nicole Lu¨hmann, Robin Panisch and Thomas Mu¨ller∗
C–C coupling reactions between arylsilanes and alkylfluorides are efficiently catalyzed by disilyl cation 1. Primary as well
as secondary alkylfluorides were quantitatively coupled with arylsilanes; however, in the case of tertiary fluorides, the
hydrodefluorination reaction predominated. Primary alkylfluorides were found to give arenes with mostly rearranged alkyl
c
substituents. In all cases subsequent Friedel–Crafts-type chemistry occurred. Copyright ꢀ 2010 John Wiley & Sons, Ltd.
Supporting information may be found in the online version of this article.
Keywords: C–F activation; organocatalysis; silyl cations; cross-coupling; silicon
Introduction
solvent. The turnover number (TON) of the strongly exothermic
process was determined to be 45. Notably, no other hydrocarbons,
in particular no rearranged products, were detected in this
reaction.[12]
In this contribution we will report on further studies of this
catalytic process using the TPFPB salt of disilyl cation 1 as catalyst.
Particular attention will be paid to the development of this process
from a pure hydrodefluorination reaction, which is in essence a
defunctionalization process, to a synthetically preferable C–C
coupling process.
The catalytic activation of the very strong C–F bond is still
a challenging topic in current catalysis research. Most work
in this field is directed towards the stoichiometric defunc-
tionalization of organic fluorides at transition metal sites.[1–5]
Several examples of catalytic cleavage of C–F bonds[6] us-
ing transition metal complexes as catalysts have been known
since the pioneering work of Milstein.[7,8] Suitable substrates
are in most cases aromatic organo fluorides. A general trend
in catalysis is the replacement of expensive and often toxic
transition metals with main group elements.[9] During the
last few years, results reported by the groups of Ozerov[10]
,
Rosenthal[11] and our group[12] have highlighted the fascinating
potential of strong Lewis acids such as sub-coordinated organosil-
icon and organoaluminum compounds in C–F bond activation
processes.[13]
Scheme 1. Catalytic hydrodefluorination reaction in excess Et3SiH as
solvent.[12]
Results and Discussion
Incourseofourinvestigationsofthecatalyzedhydrodefluorination
process (Scheme 1) we used aromatic hydrocarbons such as
benzene as solvents in an attempt to control the reaction
conditions of the strongly exothermic reaction more precisely.
The dilution of the reaction mixture is expected to allow the
effective control of experimental parameters like the reaction
temperature. In a typical experiment, 0.1 mmol of the cation
salt 1·TPFPB in benzene was prepared and a solution of the
fluorohydrocarbon (2.5 mmol) and triethylsilane (3 mmol) in
Me2Si
SiMe2
X
1: X = H; 2: X = F
Figure 1. Disilylhydronium ion 1 and disilylfluoronium ion 2.
Recently, we reported on the catalytic C–F activation of primary
and benzylic fluorohydrocarbons using tetrakispentafluorophenyl
borates (TPFPBs) of the bissilylated hydronium ion 1 or of the
fluoronium ion 2 as catalysts and Et3SiH as hydride source (see
Figure 1).[11] In the absence of an additional solvent, the reactions
yielded the corresponding alkanes as products (Scheme 1). That
is, the conversion of 1-fluorodecane into n-decane proceeded
quantitatively using 1·TPFPB as catalyst and excess Et3SiH as
∗
Correspondenceto:Thomas Mu¨ller,Institutfu¨rReineundAngewandteChemie,
¨
Carl von Ossietzky Universitat Oldenburg, Carl-von-Ossietzky-Str. 9-11, 26211
Oldenburg, Germany. E-mail: thomas.mueller@uni-oldenburg.de
¨
Institut fu¨r Reine und Angewandte Chemie, Carl von Ossietzky Universitat
Oldenburg, Carl-von-Ossietzky-Str. 9-11, 26211 Oldenburg, Germany
c
Appl. Organometal. Chem. 2010, 24, 533–537
Copyright ꢀ 2010 John Wiley & Sons, Ltd.

N. Lu¨hmann, R. Panisch and T. Mu¨ller
Table 1. Catalytic hydrodefluorination in the presence of benzene (catalyst 1, 4 mol%)
Alkylation
products
Conversion
RFa
Other
products
Entry
Substrate RF
n = 1
n = 2
n = 3
n = 4
1
n-C10H21 –F
cy-C6H11 –F
cy-C6H11 –F
1-ad–Fc
3
4
4
5
quant
quant
quant
quant
91
67
29
10
9
24
31
–
–
9
–
–
–
–
–
–
2
3b
40
–
–
90d
4
a Conversion of fluorohydrocarbon; b 1 equiv. benzene; c 1-ad: 1-adamantyl; d adamantane.
excess benzene (2 ml) was added at room temperature. After
completion of the reaction, the product mixture was separated
fromthecationsaltandanalyzedbyNMRspectroscopyandGC-MS
without further purification. In all cases, the substrates, i.e. primary,
secondary or tertiary fluorohydrocarbons (RF) were completely
consumed. When primary and secondary alkyl fluorides were used
as substrates the products of the expected hydrodefluorination
reaction, simple alkanes (RH) were however not formed. Instead,
alkylated arenes were found to be the main products (Table 1,
Scheme 2 and, for further details, see the Supporting Information).
Also in the case of the tertiary substrate 1-fluoroadamantane,
1-phenyladamantane was identified in the product mixture in
detectable amounts (10%). In this case, however, adamantane, the
product of the expected hydrodefluorination reaction, was found
to be the major component (90%).
on silyl cation-catalyzed dehydrofluorination reactions of primary
alkylfluorides[10a,b] and in contrast to our results using trialkylsi-
lanes as solvents.[12] In those cases no rearranged products were
detected,[10a,b] indicating the absence of a free carbocation as
intermediate in the catalytic cycle. Secondary substrates such as
1-fluorocyclohexane are not subject to rearrangement reactions
even in the presence of benzene, as suggested by the exclusive
formation of cyclohexyl-substituted benzene derivatives (Table 1,
entries 2 and 3). The poorer alkylating ability of the tertiary sub-
strate 1-fluoroadamantane became evident by the formation of
adamantane as the main product in the defluorination reaction of
1-fluoroadamantane. Inthiscasethereductionof theintermediate
tertiary1-adamantylcationbyEt3SiHisfavoredoverFriedel–Crafts
alkylation of the benzene solvent by the bulky carbocation.
The complete consumption of the alkyl fluorides clearly
indicates the catalytic character of the observed alkylation
reactions in each case. On the basis of our previous mechanistic
suggestion,[12] we propose a modified catalytic cycle (Scheme 3a),
according to which the alkyl fluoride is ionized by the catalyst
1. The formed carbocation (R+) reacts with the solvent benzene,
forming an arenium ion which delivers by reaction with Et3SiH the
alkylated arene and a silyl cation (R3Si+). Fluoride transfer from
the fluorodisilane 6 to the silyl cation affords the product Et3SiF
and recovers the catalyst 1. The products of this catalytic reaction,
alkylated arenes and Et3SiF were unequivocally identified (see
Supporting Information).
Although these alkylation reactions are not selective, they
combine the challenging activation of a strong C–F bond with
a highly desirable formation of a new C–C bond.[5c,10a,11,17–20]
Clearly, in order to be of preparative value, it is important to
enhance the selectivity of the C–C bond-forming reaction step.
Therefore, trimethylsilylbenzene (PhSiMe3) 7, was chosen as a
possibly suitable aromatic substrate and as the source for the
silyl cation, which is needed for the propagation of the catalytic
cycle (Scheme 3b). In addition, the ipso-directing[21] effect of the
SiMe3 group is expected to allow a regioselective alkylation of
the arene. In a typical catalysis experiment, equimolar amounts
(2 mmol) of the fluorohydrocarbon and PhSiMe3 were added
to a portion (0.1 mmol) of the hydronium ion salt 1·TPFPB.
The subsequent characterization of the crude product mixture
by GC-MS clearly showed the formation of alkylated benzene
derivatives (RnC6H6−n, Table 2); alkylated Table 1 Footnote c:1-
ad:1-adamantyl derivatives of PhSiMe3 were not detected. The
degree of alkylation varied from n = 1 to n = 4. (Complementary
to the reaction in benzene trialkylsilyl fluoride and dialkylsilyl
Scheme 2. C–F activation in alkyl fluorides by 1·TPFPB with benzene.
This finding indicates the presence of highly electrophilic alkyl
cations or their synthetic equivalents as intermediates in the
catalytic cycle. They are formed from alkyl fluorides by reaction
with the disilyl cation catalyst and they further react with the
solvent benzene in an electrophilic aromatic substitution yielding
alkylated arenes as products. Being towards electrophilic aromatic
substitution activated species, the mono-alkylated arenes are
further alkylated under the reaction conditions to give mixtures of
arenes having different alkylation grades. The degree of alkylation
of the arene solvent can be controlled to some degree by the
concentration of the substrate. That is, high concentrations of
the alkyl fluoride substrate leads to higher percentage of di- and
trialkyl substituted benzenes (compare Table 1, entries 2 and 3).
In line with the assumption of an alkyl cation as an inter-
mediate in the catalytic cycle, the attempted defluorination of
1-fluorodecane in the presence of benzene not only gave
1-phenyldecane as product. Instead 1,2-hydride shifts took place
and 2-phenyldecane and 3-phenyldecane were identified as
products by GC-MS. This result is in accordance with classical
Friedel–Crafts alkylation reactions where the attempted alkyla-
tion with primary substrates leads to the rearrangement of the
alkyl chain.[14–16] It is, however, in contrast to previous reports
c
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Appl. Organometal. Chem. 2010, 24, 533–537

A catalytic C–C bond-forming reaction
Scheme 3. Proposed catalytic cycles of the C–F activation process (a) in the presence of arenes as solvent, and (b) in the presence of PhSiMe3.
Table 2. Catalytic cross-coupling between fluorohydrocarbons and PhSiMe3 7 (catalyst 1, 4 mol%, entries 1–3) and between p-trimethylsilyltoluene
9 and fluorocyclohexane (entry 4)
Alkylation
products
Conversion
RFa
Other
products
Entry
Substrate RF
n = 1
n = 2
n = 3
n = 4
b
1
2
3
4
n-C10H21 –F
cy-C6H11 –F
1-ad–Fc
3
4
quant
quant
quant
quant
56
32
21
36
40
36
15
36
–
–
3
–
–
4
1
28
–
5
64d
cy-C6H11 –F
10
28
0
a Conversion of fluorohydrocarbon substrate;b detected, but less than 1%; c 1-ad: 1-adamantyl; d 56% Ph2SiMe2, 5% (Ad-C6H4)SiMe3, 3% adamantane.
fluoride could be detected.) This finding indicates that the first
reaction step was the desired ipso-substitution of the SiMe3 group
by the intermediate R+ (Scheme 3b). The activating effect of
the alkyl group facilitated further Friedel–Crafts-like alkylation
reactions, leading to the observed multiple substitution products.
Notably, the reaction of 1-fluorodecane with PhSiMe3 gave in
addition products resulting from rearrangement reactions of the
alkylchainaswellasasmallamountof1-phenyldecane. Inthecase
of cyclohexyl fluoride no products resulting from rearrangements
of the cyclohexyl ring were detected. This was supported by
the isolation of 1,2,4,5-tetracyclohexylbenzene from the reaction
mixture and its spectroscopic identification.[22,23]
While the reaction of fluorodecane and fluorocyclohexane
gave alkylated benzene derivatives as products, the attempted
C–C coupling of fluoroadamantane and PhSiMe3 was more
complicated. Unexpectedly, the main product is Ph2SiMe2, the
desired product phenyladamantane was only formed as a minor
product. The larger steric demand of the adamantyl substrate
made the ipso-substitution at the substrate PhSiMe3 unfavorable;
instead a Si–C bond of the SiMe3 group was cleaved by the
electrophile. However, the exact mechanism of this unexpected
reaction remains unknown.
The regioselectivity of the catalyzed C–C coupling reaction
was tested for the reaction of p-trimethylsilyltoluene 9 with
fluorocyclohexane. Using the standard procedure, in this case
not only the product of ipso-substitution of the trimethylsilyl
group was detected but subsequent electrophilic alkylation
reactionsalsogavehigheralkylatedproductsinconsiderableyields
(Table 2, entry 4). Moreover, even the monoalkylated product was
not produced regioselectively, but two different isomers were
Scheme 4. Cross-coupling reaction of p-trimethylsilyltoluene 9 to give
p-10 and suggested mechanism for the formation of o-10.
detected by GC-MS. The expected isomer p-10 which results
from ipso-substitution (C6H11 vs SiMe3) was formed in an equal
amount relative to the ortho isomer o-10. The meta regio-isomer
m-10 was not found in the product mixture.[24] In a test reaction
applying the reaction conditions of the catalyzed C–C coupling
reaction (p-10, excess fluorocyclohexane, 4% 1·TPFPB), it was
shown that pure p-10 did not rearrange to o-10. This suggests
that the ortho isomer was formed in a competitive reaction to the
ipso-substitution. A possible mechanistic rationalization for the
formation of the ortho regio-isomer is put forward in Scheme 4.
The formation of an arenium ion 11 under kinetic control might
be envisaged after two 1,2-H shifts to the thermodynamically
c
Appl. Organometal. Chem. 2010, 24, 533–537
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N. Lu¨hmann, R. Panisch and T. Mu¨ller
Table 3. Catalytic cross-coupling between fluorohydrocarbons and fluorinated arenes 13 (catalyst 1, 4 mol%)
Substrate
Me3Si–Ar
Alkylation
products
Entry
Substrate RF
n = 0
n = 1
n = 2
n = 3
n = 4
1
2
3
4
5
7
cy-C6H11 –F
cy-C6H11 –F
cy-C6H11 –F
cy-C6H11 –F
cy-C6H11 –F
4
8
28
30
35
22
–
34
21
16
–
26
15
10
–
3
1
–
–
–
13a
13b
13c
13d
14a
14a
14b
14c
52
100
100
–
–
–
more stable β-silyl substituted arenium ion 12. An intermolecular
deprotonation/reprotonationsequence,whichwoulddirectlygive
cation 12 from arenium ion 11, cannot, however, be excluded.
Finally, desilylation of arenium ion 12 occurs to form the isomer
o-10.[25]
which will severely hamper the use of this C–C coupling reaction
in synthetic organic chemistry.
Experimental
In order to inhibit the unwanted multiple alkylation products
in the C–C coupling reaction, fluorinated phenylsilanes 13
were chosen as alternative substrates. The fluorine substitution
was expected not only to block possible substitution sites,
but also to significantly deactivate the aromatic ring towards
electrophilic aromatic substitution. The results of a series of
C–C coupling experiments using fluorinated phenylsilanes with
cyclohexyl fluoride as reagent are summarized in Table 3.
Monofluorsubstitution as in 13a,b significantly decreased the
reactivity in the C–C coupling reaction, i.e. the conversion of the
phenylsilane was not quantitative. As expected, the deactivation
was more efficient for the meta regio-isomer 13b than for ortho-
fluoro-phenylsilane 13a. In both cases, however, the formation of
multiple substitution products was not suppressed. Compounds
13c,d with additional fluorine substituents were unreactive under
the applied reaction conditions.
General
Benzene and benzene-d6 were distilled from sodium. Et3SiH was
distilled freshly from calcium hydride. 1-Fluorocyclohexane and 1-
fluorodecane were distilled from P4O10. All reactions were carried
out under inert conditions. 1·TPFPB was prepared as described
previously.[12] NMR spectra were recorded on a Bruker Avance 250
spectrometer at T = 300 K. GC-MS analyses were carried out on
a coupled system, with a Thermo Focus gas chromatograph (DB5
column, length 25 m, inner diameter 0.2 mm) and a Thermo DSQ
(EI) mass spectrometer.
Catalyzed hydrodefluorination reaction of alkylfluorides
in the presence of benzene
A solution of 0.1 mmol 1·TPFPB in 2 ml benzene was added
to a mixture of 2.5 mmol fluorohydrocarbon (1-fluorodecane,
fluorocyclohexane, 1-fluoroadamantane) and 3 mmol Et3SiH at
room temperature. The crude product mixture was characterized
by NMR spectroscopy and GC-MS.
Conclusion
Catalytic activation of C–F functionalities in fluoroalkanes using
the TPFPB salt of disilylcation 1 is a very efficient process which
proceeds at room temperature in high rates with reasonable
turnover numbers in trialkylsilanes as solvent.[12] In aromatic
solvents the high reactivity of the catalyst prevails; however,
Friedel–Crafts-type reactions between intermediate carbocations
and the arene solvent become predominant and result in mixtures
of different alkyl arene regio-isomers with partially rearranged
alkyl substituents. Therefore, the intriguing combination between
activation of an aliphatic C–F bond and a C–C bond forming
process in this reaction is obscured by the intractable reaction
mixtureobtained.Thisdichotomycanberesolvedusingarylsilanes
as substrates and as the source for the silyl cation, which
is needed for the propagation of the catalytic cycle. The
reaction of trimethylphenylsilane with primary, secondary and
tertiary alkylfluorides which yields C–C coupling products indeed
demonstrates in principle the validity of this approach. The high
reactivity of the so-formed alkyl arenes towards Friedel–Crafts-
type alkylation processes, however, leads to subsequent reactions
Catalyzed C–C cross coupling between arylsilanes
and alkylfluorides
An equimolar mixture of 2.5 mmol fluorohydrocarbon and
2.5 mmol phenyltrimethylsilane was added to 0.1 mmol 1·TPFPB
at −10 ◦C and stirred for 2 min. The reaction mixture was warmed
to room temperature and stirred for 30 min. The crude product
mixture was characterized by NMR spectroscopy and GC-MS.
Because of the low solubility of 1-fluoroadamantane in
phenyltrimethylsilane, a solution of 2 mmol 1-fluoroadamantane
in 3.5 ml phenyltrimethylsilane was added to 0.1 mmol 1·TPFPB at
−10 ◦C. After warming to room temperature, the crude product
mixture was characterized by NMR spectroscopy and GC-MS.
Acknowledgments
This work was supported by the Deutsche Forschungsgemein-
schaft (MU1440/6-1).
c
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A catalytic C–C bond-forming reaction
Supporting information
[14] G. A. Olah, Friedel–Crafts Chemistry, Wiley: New York, 1973.
[15] G. A. Olah, R. Krishnamurti, G. K. S. Prakash, in Comprehensive
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Press: Oxford, 1991, p. 293.
[16] G. A. Olah, A. Molnar, Hydrocarbon Chemistry, 2nd edn, Wiley-
Interscience: Hoboken, NJ, 2003.
Supporting information can be found in the online version of this
article.
[17] V. P. W. Bo¨hm, C. W. K. Gsto¨ttmayr, T. Weskamp, W. A. Herrmann,
Angew. Chem. Int. Ed. 2001, 113, 3500; Angew. Chem. Int. Ed. 2001,
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[18] T. Braun, R. N. Perutz, M. I. Sladek, Chem. Commun. 2001, 2254.
[19] T. Schaub, M. Backes, U. Radius, J. Am. Chem. Soc. 2006, 128, 15964.
[20] A. Steffen, M. I. Sladek, T. Braun, B. Neumann, H.-G. Stammler,
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[21] A. R. Bassindale, S. J. Glynn, P. G. Taylor, in The Chemistry of Organic
Silicon Compounds, Vol. 2 (Eds.: Z. Rappoport, Y. Apeloig), Wiley:
New York, 1998, pp. 355.
[22] J. T. Mague, L. Linhardt, I. Medina, D. J. Sattler, M. J. Fink, Acta
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c
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