Ruthenium chloride as an efficient catalytic precursor for hydroarylation reactions via C-H bond activation

Article abstract of DOI:10.1021/ol101038c

A very simple and efficient catalytic system for the hydroarylation of olefins by aromatic ketones and Michael acceptors using simple and inexpensive ruthenium trichloride as a ruthenium source is described. These very mild conditions (dioxane at 80 -°C)

Full text of DOI:10.1021/ol101038c

ORGANIC
LETTERS
2010
Vol. 12, No. 13
3038-3041
Ruthenium Chloride as an Efficient
Catalytic Precursor for Hydroarylation
Reactions via C-H bond Activation
Marc-Olivier Simon, Jean-Pierre Genet, and Sylvain Darses*
Laboratoire Charles Friedel (UMR 7223), Ecole Nationale Supe´rieure de Chimie de
Paris, 11 rue P&M Curie, 75231 Paris Cedex 05, France
sylVain-darses@chimie-paristech.fr
Received May 6, 2010
ABSTRACT
A very simple and efficient catalytic system for the hydroarylation of olefins by aromatic ketones and Michael acceptors using simple and
inexpensive ruthenium trichloride as a ruthenium source is described. These very mild conditions (dioxane at 80 °C) appeared to be highly
compatible, tolerant, and selective toward various functional groups, and the ease of the protocol is highly convenient for synthetic purposes.
Carbon-carbon bond-forming reactions involving carbon-
hydrogen bond activation catalyzed by transition-metal
complexes have arisen as a very powerful methodology to
build complex molecules.1 These reactions allow the use of
readily available substrates, since no preliminary function-
alization is needed, and lead to clean reactions with atom
economy.2 Several transition-metal complexes like ruthe-
nium, rhodium, iridium, and palladium have demonstrated
a high activity for such catalytic reactions,3 and among them,
ruthenium complexes were revealed to be of high interest
in term of cost and efficiency.
More particularly, hydroarylation reactions, have been
developed using low-valent ruthenium complexes such as
RuH2(CO)(PPh3)3, RuH2(PPh3)4, Ru(CO)2(PPh3)3, Ru3(CO)12,
and RuH2(H2)2(PCy3)2, for example.4,5 However, these cata-
lysts are generally air and moisture sensitive and must be
stored under inert atmosphere at low temperature to prevent
decomposition. Moreover, they usually require several
(1) Reviews: (a) Shilov, A. E.; Shul’pin, G. B. Chem. ReV. 1997, 97,
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Sabo-Etienne, S.; Chaudret, B. Eur. J. Inorg. Chem. 1999, 1047. (d) Jia,
C.; Kitamura, T.; Fujiwara, Y. Acc. Chem. Res. 2001, 34, 633. (e) Ritleng,
V.; Sirlin, C.; Pfeffer, M. Chem. ReV. 2002, 102, 1731. (f) Kakiuchi, F.;
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Kan, S.; Chatani, N. J. Am. Chem. Soc. 2005, 127, 5936. (b) Stuart, D. R.;
Fagnou, K. Science 2007, 316, 1172. (c) Shi, B.-F.; Maugel, N.; Zhang,
Y.-H.; Yu, J.-Q. Angew. Chem., Int. Ed. 2008, 47, 4882. (d) Yang, S.-D.;
Sun, C.-L.; Fang, Z.; Li, B.-J.; Li, Y.-Z.; Shi, Z.-J. Angew. Chem., Int. Ed.
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10.1021/ol101038c  2010 American Chemical Society
Published on Web 06/04/2010

preparation and purification steps from commercial ruthe-
nium chloride, and their fixed structure does not allow the
steric and electronic properties of the catalytic active
ruthenium species to be tuned by a proper choice of the
ligand. We recently developed an alternative and more
convenient protocol6 consisting of the in situ generation of
the ruthenium active catalyst from a stable and commercial
ruthenium source [RuCl2(p-cym)]2 (p-cym ) p-cymene),
sodium formate as a reducing agent, and a phosphane ligand.
This catalytic system turned out to be very efficient for the
hydroarylation of styrenes and vinylsilanes by aromatic
ketones and imines6,7 and for the hydroalkenylation of
vinylsilanes by Michael acceptors.8
Table 1. Optimization of the Reaction Conditionsa
entry
solvent
toluene
cyclohexane
i-PrOH
i-PrOH/acetone 1:1
dioxane
dioxane
temp (°C)
conversionb (%)
1
2
3
4
5
6
reflux
reflux
reflux
reflux
reflux
80
67
52c
78c
71
92
99 (80)d
We wondered whether ruthenium chloride could be used as
the ruthenium source in our catalytic system. Besides the
practical advantages of such a precursor, its cost (2.7 €/mmol)
would represent a significant benefit owing to the prohibitive
price of commonly used ruthenium catalysts: RuH2(CO)(PPh3)3
(87 €/mmol), RuH2(PPh3)4 (160 €/mmol), Ru3(CO)12 (38
€/mmol), and [RuCl2(p-cym)]2 (21 €/mmol).9
a Reaction conditions: 1a (1 mmol), 2a (2 mmol), RuCl3.xH2O (4 mol
% of Ru), NaHCO2 (30 mol %), and PPh3 (15 mol %) for 20 h at the
indicated temperature. b Conversions were determined by GC using an
internal standard. c Including 5% of acetophenone reduction product.
d Isolated yield is shown in parentheses.
starting from ruthenium(II) precursor, resulted in low conver-
sion. The use of 2-propanol as solvent7c led to the hydroary-
lation product 3aa though with a moderate 73% conversion
along with 5% of acetophenone reduction product (entry 3).
As expected, the use of a 1:1 mixture of 2-propanol/acetone
inhibited the formation of the reduction byproduct but did
not increase the conversion (entry 4).12 On the other hand,
conducting the reaction in refluxing dioxane allowed the
formation of 3aa with a high 92% conversion (entry 5).
Moreover, the reaction temperature could be reduced to 80
°C, and the expected hydroarylation product 3aa was isolated
in 80% yield.
Ruthenium chloride has often been used as an in situ
precursor in hydrogenation reactions,10 but in the field of
carbon-carbon bond formation, only a few examples have
been reported.11 We describe here the first example of
alkylation of aromatic ketone by ortho carbon-hydrogen
bond activation (Murai reaction)4 starting from ruthenium
chloride as a ruthenium source.
The main challenge consists of the reduction of ruthe-
nium(III) to ruthenium(II) which would then likely undergo
the same evolution as [RuCl2(p-cym)]2 to generate the
ruthenium-active species for the hydroarylation reaction.7b
We first examined the role of the solvent on the reaction of
4-methylacetophenone (1a) and triethoxyvinylsilane (2a) in
the presence of RuCl3·xH2O, sodium formate, and triph-
enylphosphane at 80 °C for 20 h (Table 1). The use of
nonpolar solvents (toluene or cyclohexane, entries 1 and 2),
which were particularly adapted using a similar system but
(4) (a) Murai, S.; Kakiuchi, F.; Sekine, S.; Tanaka, Y.; Kamatani, A.;
Sonoda, M.; Chatani, N. Nature 1993, 366, 529. (b) Kakiuchi, F.; Sekine,
S.; Tanaka, Y.; Kamatani, A.; Sonoda, M.; Chatani, N.; Murai, S. Bull.
Chem. Soc. Jpn. 1995, 68, 62. (c) Sonoda, M.; Kakiuchi, F.; Chatani, N.;
Murai, S. Bull. Chem. Soc. Jpn. 1997, 70, 3117. (d) Kakiuchi, F.; Murai,
S. Acc. Chem. Res. 2002, 35, 826.
(5) (a) Grutters, M. M. P.; Mu¨ller, C.; Vogt, D. J. Am. Chem. Soc. 2006,
128, 7414. (b) Tsai, A. S.; Bergman, R. G.; Ellman, J. A. J. Am. Chem.
Soc. 2008, 130, 6316. (c) Harada, H.; Thalji, R. K.; Bergman, R. G.; Ellman,
J. A. J. Org. Chem. 2008, 73, 6772. (d) McKeown, B. A.; Foley, N. A.;
Lee, J. P.; Gunnoe, T. B. Organometallics 2008, 27, 4031. (e) Kuninobu,
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64, 5974. (f) Luedtke, A. T.; Goldberg, K. I. Angew. Chem., Int. Ed. 2008,
47, 7694. (g) Nakao, Y.; Kashihara, N.; Kanyiva, K. S.; Hiyama, T. J. Am.
Chem. Soc. 2008, 130, 16170. (h) Kozhushkov, S. I.; Yufit, D. S.;
Ackermann, L. Org. Lett. 2008, 10, 3409. (i) Vasylyev, M.; Alper, H.
Angew. Chem., Int. Ed. 2009, 48, 1287. (j) Kubiak, R.; Prochnow, I.; Doye,
S. Angew. Chem., Int. Ed. 2009, 48, 1153.
Figure 1. Influence of the ligand (12 mol %) in the reaction of 1a
with 2a using in situ generated ruthenium catalyst from RuCl3·xH2O
(4 mol % Ru) at 80 °C in dioxane: (4-CF3C6H4)3P, gray diamonds;
(4-ClC6H4)3P, black triangles; [3,5-(CF3)2C6H4]3P, gray squares;
Ph3P, black diamonds; (4-MeOC6H4)3P, gray circles.
(6) Martinez, R.; Chevalier, R.; Darses, S.; Genet, J.-P. Angew. Chem.,
Int. Ed. 2006, 45, 8232.
(7) (a) Martinez, R.; Genet, J.-P.; Darses, S. Chem. Commun. 2008, 3855.
(b) Martinez, R.; Simon, M.-O.; Chevalier, R.; Pautigny, C.; Genet, J.-P.;
Darses, S. J. Am. Chem. Soc. 2009, 131, 7887. (c) Simon, M.-O.; Martinez,
R.; Genet, J.-P.; Darses, S. J. Org. Chem. 2010, 75, 208
.
(8) Simon, M.-O.; Martinez, R.; Genet, J.-P.; Darses, S. AdV. Synth.
Taking advantage of the versatility of this catalytic system,
the role of the phosphane ligand was then investigated. Several
triarylphosphane derivatives were evaluated (Figure 1), and we
Catal. 2009, 351, 153.
(9) Lowest prices quoted from Aldrich Chemistry, Alfa Aesar, and Strem
Chemicals, 2009.
Org. Lett., Vol. 12, No. 13, 2010
3039

P(4-CF3C6H4)3, whereas PPh3 led to less than 10% conversion
in the same time. Therefore, electron-deficient ligands seemed
to be more appropriate in this reaction as we noticed before
when using [RuCl2(p-cym)]2.7b Moreover, variable induction
periods were observed depending on the electronic structure of
the ligand (e.g., 1 h for P(4-ClC6H4)3 and more than 5 h for
PPh3), which are consistent with the likely decisive role of the
ligand in the reduction of ruthenium(III) precursor that has
already been proposed.11c,13
Table 2. Scope of the Reactiona
These optimized conditions, using P(4-CF3C6H4)3 as ligand
and dioxane as solvent, were tested in the reaction of a variety
of aromatic ketone substrates with triethoxyvinylsilane and
proved to be very general (Table 2). Acetophenone (1b) was
efficiently alkylated in the presence of 5 mol % of ruthenium
chloride hydrate in dioxane at 80 °C with 91% yield (entry 1).
Ethoxybenzyl-substituted ketone 1c reacted readily (entry 2),
which contrasts with previous results at 140 °C in toluene where
a poor conversion was obtained, presumably due to side
reactions at such higher temperature.6 Hydroarylation with para-
substituted aromatic ketones proceeds easily with either electron-
donating (entry 4) or -withdrawing (entry 3) substituents. With
3-methoxyacetophenone (1f), activation occurred selectively at
the most hindered position, as was already reported, due to the
chelating properties of the methoxy group.4,6,7 The reaction
with ortho-substituted ketones offered good yields (entries
6 and 7) such as the functionalized tetralone derivative 1i
(entry 8). Interestingly, the presence of bromo (entry 3) and
even iodo (entry 8) substituents on the aromatic groups did
not interfere with the C-H activation process, affording
substrates that could be further functionalized by cross-
coupling reactions. Various heteroaromatic ketones, including
2-acetylfuran (1j) (entry 9), 2-acetylthiophene (1k) (entry
10), and N-acetyl-3-acetylindole (1 L) (entry 11), participated
in the reaction, affording moderate to good yields of
hydroarylation products.
Scheme 1. Activation of the ꢀ C-H Bond of
tert-Butylcrotonamide Leading to Allylsilane
a Reaction conditions: 1 (1 mmol), 2 (2 mmol), RuCl3·xH2O (4 mol %
Ru), NaHCO2 (30 mol %) and P(4-CF3C6H4)3 (15 mol %) in dioxane at 80
°C for 20 h. b Yields of isolated products; mono- and disubstituted ratio
given between parentheses. c Formation of the 1,2 regioisomer. d The
reaction was conducted for 68 h.
observed that the ligand significantly influenced the reaction
rates since a complete conversion was obtained within 6 h with
The activation of the ꢀ C-H bond of tert-butylcrotonamide
1m was also achieved very efficiently leading to the corre-
sponding allylsilane 3ma with a satisfactory yield of 78%
(Scheme 1), which constitutes an improved yield compared to
that obtained using the previous catalytic system.8
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Org. Lett., Vol. 12, No. 13, 2010

Markovnikov (linear) adduct was obtained in a high yield
and with 90% selectivity, results which are similar to what
we previously reported.7a
Table 3. Hydroarylation of Other Olefinsa
In conclusion, we have developed a very simple catalytic
system for the hydroarylation of olefins by aromatic ketones
and Michael acceptors. This catalytic system generates in
situ an active ruthenium species from inexpensive ruthenium
chloride hydrate, sodium formate, and tri(4-trifluorometh-
ylphenyl)phosphane. These very mild conditions (dioxane
at 80 °C) appeared to be highly compatible, tolerant, and
selective toward various functional groups, and the ease of
the protocol would make it very convenient for synthetic
purposes. The mechanism for the generation of the active
ruthenium species from ruthenium chloride is still unclear
and is currently under investigation.
Acknowledgment. This work was supported by the Centre
National de la Recherche Scientifique (CNRS). M.-O.S.
thanks the Ministe`re de l’Education et de la Recherche for
a grant.
a Reaction conditions: 1 (1 mmol), 2 (2 mmol), RuCl3·xH2O (4 mol %
of Ru), NaHCO2 (30 mol %), and P(4-CF3C6H4)3 (15 mol %) in dioxane at
80 °C for 20 h. b Yields of isolated products. c Reaction conducted at 100
°C. d The reaction was carried out at 140 °C with 3 equiv of styrene.
e Proportion of the anti-Markovnikov product between parentheses.
Supporting Information Available: Experimental pro-
cedures and compound descriptions. This material is available
free of charge via the Internet at http://pubs.acs.org.
The reaction of other compatible olefins was also inves-
tigated (Table 3). R-Tetralone (1n) reacted with vinylsilanes
derivatives (entries 1-3) leading to the alkylated product
with very good yields. The reaction of styrene (2e) was also
evaluated with 4-methylacetophenone (entry 4), and the anti-
OL101038C
(13) (a) Tilley, T. D.; Grubbs, R. H.; Bercaw, J. E. Organometallics
1984, 3, 274. (b) Goossen, L. J.; Arndt, M.; Blanchot, M.; Rudolphi, F.;
Menges, F.; Niedner-Schatteburg, G. AdV. Synth. Catal. 2008, 350, 2701.
Org. Lett., Vol. 12, No. 13, 2010
3041