Ruthenium(II)-catalyzed alkenylation of ferrocenyl ketones via C-H bond activation

Article abstract of DOI:10.1021/om3008162

The alkenylation with alkyl acrylates of ferrocenyl alkyl ketones is performed with the [RuCl₂(p-cymene)]₂ /AgSbF₆ catalytic system and leads, via ferrocene C-H bond activation, to moderate yields of the 1,2-disubstituted

Full text of DOI:10.1021/om3008162

Communication
pubs.acs.org/Organometallics
Ruthenium(II)-Catalyzed Alkenylation of Ferrocenyl Ketones via C−H
Bond Activation
Keisham S. Singh and Pierre H. Dixneuf*
Centre of catalysis and Green chemistry-OMC, Institut Sciences Chimiques de Rennes, UMR 6226, CNRS-universite
Campus de Beaulieu, 35042 Rennes, France
́
de Rennes 1,
S
* Supporting Information
ABSTRACT: The alkenylation with alkyl acrylates of
ferrocenyl alkyl ketones is performed with the [RuCl2(p-
cymene)]2 /AgSbF6 catalytic system and leads, via ferrocene
C−H bond activation, to moderate yields of the 1,2-
disubstituted ferrocene derivatives in the presence of Cu-
(OAc)2·H2O under aerobic conditions at 80−110 °C. The
alkenylation of ferrocenyl phenyl ketone, in contrast, takes
place at room temperature to afford quantitative yields of the
phenyl monoalkenylated product, demonstrating the strong
influence of the ferrocenyl group on arene C−H bond
functionalization. Small amounts of 2-alkenylferrocenyl 2′-
phenyl ketones can also be obtained.
unctional ferrocene derivatives constitute a family of
chemicals offering useful properties in several areas. They
catalyst in acetic acid, leading only to moderate yields in
monoalkenylated ferrocenes.11 In contrast, in the presence of a
directing dimethylaminomethyl group, ferrocene C−H bonds
were recently functionalized with Pd(II) catalyst on reaction
with diarylacetylenes to give highly arylated naphthalenes,12
and effective borylation of ferrocene C−H bonds has been
performed with iridium catalyst.13
F
are the basis of practical ligands,1 including planar chirality
ligands for efficient enantioselective catalysis.2 They have found
applications in material science as metallocene-containing
polymers3 and as materials for optical applications.4 Most of
the synthetic methods functionalizing ferrocene involve either a
Friedel−Crafts type electrophilic substitution or a stoichio-
metric C−H bond metalation followed by coupling with an
electrophile.5 It thus remains a challenge to develop new,
general catalytic methods to derivatize the stable ferrocene
derivatives.
Recently it was shown that stable and inexpensive
ruthenium(II) catalysts could promote the alkenylation of
arene and heterocycle C−H bonds directed by several
functional groups14,15 and that the modification of RuCl2Ln
complexes with silver salts allowed the alkenylation of weakly
coordinating aryl ketones at 110 °C.16 These observations were
attractive to explore the direct functionalization of ferrocenyl
derivatives with halide-free ruthenium(II) catalysts. Here we
report for the first time a ruthenium(II)-catalyzed ferrocene C−
H bond alkenylation producing new bifunctional 1,2-disub-
stituted ferrocene derivatives, although in very moderate yields;
surprisingly, the ferrocenyl group favors the ruthenium
alkenylation of the phenyl C−H bond of ferrocenyl aryl
ketone, which can be performed this time quantitatively at
room temperature.
The direct catalytic sp2 C−H bond activation/functionaliza-
tion of arenes and heterocycles has considerably improved
synthetic methods via selective C−C bond cross-couplings.6 In
contrast, simple ferrocene derivatives have shown resistance to
their catalytic C−H bond functionalization, likely due to the
electron richness of this metallocene and its inertness to C−H
bond deprotonation via a concerted metalation−deprotonation
process.7 However, several examples of stoichiometric C−H
bond activation of ferrocene derivatives leading to cyclo-
metalated complexes have been reported.8
Only a few reports have already demonstrated the possibility
of catalytic ferrocene C−H bond functionalization leading to
arylated and alkenylated products. Ferrocene itself was first
alkenylated by Moritani and Fujiwara9 with Pd(OAc)2 catalyst
in dioxane/AcOH solvent in modest yields. A cross-coupling
reaction between two C−H bonds of ferrocenyloxazoline and
of an arene has been performed using a stoichiometric amount
of Pd(OAc)2, but in the additional presence of Cu(OAc)2 the
cross-coupling became catalytic and led to a good yield of the
diarylated ferrocene.10 Recently the direct alkenylation of
ferrocene with acrylates has been observed with Pd(OAc)2
The alkenylation of ferrocenyl alkyl ketones 1 and 2 was first
investigated in the presence of ruthenium(II) catalyst using
various additives to modify the Ru−Cl bonds and oxidants to
regenerate the ruthenium(II) species. The reaction of
ferrocenyl methyl ketone 1 (0.25 mmol) with an excess of
ethyl acrylate (4 equiv) in the presence of [RuCl2(p-cymene)]2
(8 mol %) catalyst precursor in dichloroethane was investigated
Received: August 23, 2012
© XXXX American Chemical Society
A
dx.doi.org/10.1021/om3008162 | Organometallics XXXX, XXX, XXX−XXX

Organometallics
Communication
Scheme 1. Ruthenium(II)-Catalyzed Alkenylation of Alkyl Ferrocenyl Ketones 1 and 2
Scheme 2. Ruthenium(II)-Catalyzed Alkenylation of Ferrocenyl Phenyl Ketone 11
(Scheme 1). With additional Cu(OAc)2·H2O alone or AgSbF6
alone no reaction occurred, but with both additives the 2-
monoalkenylated acetylferrocene complex 4 was isolated in a
moderate yield of 26% after 24 h of reaction at 100 °C (Scheme
1). The replacement of AgSbF6 by AgOTf or KPF6 did not lead
to an active catalyst, and the use of Ru(O2CCF3)2(p-cymene)
as catalyst precursor with Cu(OAc)2·H2O was not efficient.
Among the evaluated oxidants, Cu(OAc)2·H2O was found to
be effective in air. In the absence of air a very low conversion to
the desired product was obtained. Optimal reaction conditions
were found with 5 equiv of AgSbF6 with respect to [{RuCl2(p-
cymene)}2] for the generation of dicationic active ruthenium-
(II) species. These experiments revealed that the oxidant
Cu(OAc)2·H2O is operative but that only AgSbF6 leads to an
active catalyst, likely by efficient chloride abstraction in the
C−H bond activation, directed by a weakly coordinating ketone
group, can be promoted for the first time by ruthenium(II)
catalyst.
The ferrocenyl ketones 1 and 2 were reacted with several
alkyl acrylates. In a typical reaction, ferrocenyl alkyl ketone
(0.25 mmol) reacts with alkyl acrylate (0.1 mmol) in the
presence of [RuCl2(p-cymene)]2 (8 mol %)/AgSbF6 (40 mol
%) and Cu(OAc)2·H2O (2 equiv) in DCE at 110 °C for 24 h to
provide the oxidative dehydrogenative coupling products
(Scheme 1, Table SI-2 (Supporting Information)). The
acetylferrocene 1 leads to monoalkenylated acetyl ferrocenes
3−6 in 21−26% isolated yields. Analogously, the ferrocenyl
ethyl ketone 2 leads to the alkenylated products 7−10 in 14−
26% isolated yields. This reaction proceeds in almost equal
efficiency in a dioxane/acetic acid solvent mixture or DCE but
not in pure acetic acid. A decrease of reaction temperature to
presence of noncoordinating anion (SbF6 vs OTf−), and that
−
even if very moderate yields are obtained, the ferrocene ortho
B
dx.doi.org/10.1021/om3008162 | Organometallics XXXX, XXX, XXX−XXX

Organometallics
Communication
Scheme 3. Ruthenium(II)-Catalyzed Alkenylation of Ferrocenyl Phenyl Ketone 11 with Acrylate
80 °C but for a longer time results in similar yields (see Table
SI-2 in the Supporting Information).
perform, and 47% of 16 after 24 h at 80 °C and 30% of 17 after
1
30 h at 100 °C were obtained (Scheme 2). The H NMR
The structures of derivatives 3−10 are consistent with those
of 1,2-disubstituted ferrocene derivatives, as shown by 1H
NMR. All compounds show, in addition to the COR and CH
CHCO2R proton signals, a singlet for the C5H5 ligand at δ
∼4.1−4.2 ppm and for the disubstituted cyclopentadienyl
group three C5H3 consecutive coupled protons with the central
proton appearing as a pseudotriplet. For example, the 1H NMR
spectrum of compound 3 shows the C5H3 protons at δ 4.66,
4.86, and 4.90 for H3, H4, and H5, respectively, with an integral
ratio of 1:1:1, as compared with two multiplets at 4.50 and 4.70
ppm observed for the starting ketone (C5H5)Fe(C5H4COCH3)
(1). The 13C NMR spectral data of 3 showed signals at 80.20,
78.48, 74.38, 72.64, and 70.28 ppm assignable to the carbons of
the disubstituted cyclopentadienyl ring, as compared to only
three signals observed for the starting ferrocenyl methyl ketone
1.
This 1,2-disubstitution in compounds 3−10 is consistent
with the directing capability of the ketone group to activate the
neighboring ortho C−H bond. In addition, the C−H bonds of
the acyl cyclopentadienyl group are expected to be more acidic
than those of the C5H5 ring and thus both higher C−H bond
acidity and a directing coordinating ketone group favor ortho
C−H bond deprotonation/functionalization of the C5H4COR
ring only and formation of bifunctional 1,2-disubstituted
ferrocenes.
The oxidative dehydrogenative cross-coupling of methyl
acrylate with the ketone FcCOPh (11) has then been
investigated to compare the competitive alkenylation of the
ferrocenyl versus the phenyl ring. When the reaction of 11
(0.125 mmol) and methyl acrylate was performed in the
presence of [RuCl2(p-cymene)]2 (0.02 mmol, 16 mol %) and
AgSbF6 (0.1 mol) at room temperature in air for 18 h, it resulted
in the quantitative formation of the phenyl monoalkenylated
compound 12 exclusively, isolated in 93% yield (Scheme 2).
When the catalyst loading was decreased to 8 mol %, the
reaction needed 36 h at room temperature to reach complete
conversion and 12 was then isolated in 80% yield. A further
decrease of catalyst loading to 4 mol % with a reaction time of
48 h led to compound 12 in 74% yield, showing that a high
loading of 16 mol % of catalyst is required to reach a complete
transformation in 18 h.
With the above optimized reaction conditions based on
[RuCl2(p-cymene)]2 (16 mol %), in air at room temperature, the
ketone 11 reacts with various alkyl acrylates, leading to the
isolation of the phenyl monoalkenylated derivatives 13−15
isolated in 82, 97, and 86% yields after 24, 24, and 30 h at room
temperature, respectively. The monoalkenylations of 11 with
acrylonitrile and p-tert-butylstyrene were more difficult to
showed that the phenyl group was monoalkenylated and that
the C5H5 and C5H4COR group signals were retained.
The alkenylation of arene sp2 CH bonds catalyzed by a
ruthenium(II) complex in the presence of silver salt was
recently reported for aryl alkyl ketones at 110 °C for 12 h.16
Here the alkenylation of the phenyl group of the ferrocenyl
phenyl ketone is performed under much milder reaction
conditions at room temperature for 18−30 h. In order to give
more evidence for the profitable influence of the ferrocenyl
group on the alkenylation of arenes, the reaction of
benzophenone with methyl acrylate was carried out under the
same conditions as in Scheme 2. Benzophenone reacts with 4
equiv of methyl acrylate in the presence of [RuCl2(p-
cymene)]2/5 AgSbF6 catalyst, leading to the isolation of
ortho-monoalkenylated benzophenone 22 in 13% yield after 24
h at room temperature. These results show that, in the
alkenylation of ferrocenyl phenyl ketone 11, the ferrocenyl
group actually activates the alkenylation of the phenyl group
such a way that it allows the dehydrogenative alkenylation of an
aromatic ketone to occur for the first time at room temperature.
A possible explanation is that, in the presence of an oxidant, the
ferrocenyl group can be oxidized into ferrocenium ion,1,12 an
electron-withdrawing group facilitating alkenylation of the
arene group.
The partial dialkenylation of FcCOPh (11) with an excess of
alkyl acrylates was attempted by increasing the temperature and
time to 50−60 °C for 24−48 h. The reaction leads to only
small amounts of dialkenylated products 18−21 that were
separated in low yields of 14, 8, 15, and 13%, respectively, from
the previous monoalkenylated products 12−15 isolated in 80,
83, 70, and 80% yields, respectively (Table SI-3 in the
Supporting Information). The dialkenylated compounds 18−
21 can also be obtained by the reaction of 12−15 with the
corresponding acrylate in the presence of [RuCl2(p-cymene)]2
and AgSbF6. For example, compound 18 has been prepared and
isolated in only 13% yield by reacting 12 with methyl acrylate in
the presence of [RuCl2(p-cymene)]2/AgSbF6 at 50 °C for 48 h
(Scheme 3).
Compounds 18−21 have been isolated by column
chromatography and characterized by spectroscopic data. The
identity of compounds 18−21 was confirmed by NMR analysis
(1H and 13C). The proton NMR spectrum of 21 showed signals
at 5.00 and 4.22 ppm and a triplet at 4.66 ppm with integral
ratios of 1:1:1, indicating the presence of a 1,2-disubstituted
ferrocene ring.
In conclusion, we have described for the first time the still
difficult to perform ruthenium(II)-catalyzed alkenylation of
ferrocenyl alkyl ketone with alkenes via ferrocene C−H bond
C
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Communication
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ASSOCIATED CONTENT
■
S
* Supporting Information
Text, figures, and tables giving general experimental procedures,
characterization data (1H, 13C) of all compounds, and H and
1
13C NMR spectra for compounds 6, 7, and 12−18. This
material is available free of charge via the Internet at http://
pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
*E-mail: pierre.dixneuf@univ-rennes1.fr.
■
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We are grateful to the CNRS, the French Ministry for Research,
the institut Universitaire de France (P.H.D.), and the ANR
Program 09-Blanc-0101-01 for support and DST India for a
BOYSCAST fellowship to K.S.S.
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