Chelate-assisted oxidative coupling reaction of arylamides and unactivated alkenes: Mechanistic evidence for vinyl C-H bond activation promoted by an electrophilic ruthenium hydride catalyst

Article abstract of DOI:10.1021/om100764c

The cationic ruthenium hydride complex [(η⁶-C ₆H₆)(PCy₃)(CO)RuH]⁺BF ₄^- was found to be a highly regioselective catalyst for the oxidative C-H coupling reaction of aryl-substituted amides and unactivated alkenes to give o-alkenylamide products. The kinetic and spectroscopic analyses support a mechanism involving a rapid vinyl C-H activation followed by a rate-limiting C-C bond formation step.

Full text of DOI:10.1021/om100764c

5748 Organometallics 2010, 29, 5748–5750
DOI: 10.1021/om100764c
Chelate-Assisted Oxidative Coupling Reaction of Arylamides and
Unactivated Alkenes: Mechanistic Evidence for Vinyl C-H Bond
Activation Promoted by an Electrophilic Ruthenium Hydride Catalyst
Ki-Hyeok Kwon, Do W. Lee, and Chae S. Yi*
Department of Chemistry, Marquette University, Milwaukee, Wisconsin 53201-1881, United States
Received August 6, 2010
Summary: The cationic ruthenium hydride complex [(η6-C6H6)-
(PCy3)(CO)RuH]þBF4- was found to be a highly regioselective
catalyst for the oxidative C-H coupling reaction of aryl-substi-
tuted amides and unactivated alkenes to give o-alkenylamide
products. The kinetic and spectroscopic analyses support a
mechanism involving a rapid vinyl C-H activation followed by
a rate-limiting C-C bond formation step.
be most versatile in mediating Heck-type C-H alkenylation of
heteroarene compounds, where the regioselectivity has often
been found to be dictated by both the steric and electronic nature
of the arene substituents and chelate directing groups.6 Still,
most of these oxidative C-H coupling methods require either a
stoichiometric amount of metal oxidants or reactive reagents,
and the development of oxidative coupling methods which do
not require strong oxidizing agents or reactive substrates would
increase the synthetic efficiency and thus be beneficial from an
environmental point of view. We recently discovered that the
cationic ruthenium hydride complex [(C6H6)(CO)(PCy3)-
Chelate-assisted catalytic C-H activation reactions have
emerged as some of the most powerful functionalization meth-
ods for arene compounds.1 Among the chelate-directed catalytic
methods, oxidative C-H coupling reactions have been found to
be particularly effective in forming new C-C and carbon-
heteroatom bonds to arene compounds.1d,e Since Fujiwara’s
seminal reports on the arene coupling reactions,2 oxidative
C-N, C-O, and C-halogen bond-forming reactions of arene
compounds have been achieved by using oxygen and nitrogen
chelate directing groups.3 Fagnou achieved a number of regio-
selective cross-coupling reactions of unactivated arene com-
pounds by using nitrogen directing groups.4 Yu recently
developed a remarkably selective C-H olefination of carboxy-
directed arene compounds by screening amino acid ligands for
Pd catalysts.5 Late-transition-metal catalysts have been found to
-
RuH]þBF4 (1) is a highly effective catalyst precursor for a
number of coupling reactions of aryl ketones and alkenes
involving vinyl C-H activation.7 Herein we report a ruthe-
nium-catalyzed oxidative C-H coupling reaction of arylamides
with unactivated alkenes that does not require external oxidizing
agents or additives.
Initially, the coupling reaction of an arylamide and a simple
alkene was used to screen the catalyst activity (eq 1). Thus, the
treatment of N,N-dimethylbenzamide (0.5 mmol) with an excess
amount of cyclopentene (2.5 mmol) in the presence of a metal
catalyst (5 mol %) in CH2Cl2 was analyzed by GC after 5 h of
reaction time at 80 °C.8 Among the selected ruthenium catalysts,
the complex 1 exhibited uniquely high activity and selectivity for
the oxidative coupling product 2a over the o-C-H insertion
product 3a (Table S1, Supporting Information). Both CH2Cl2
and PhCl were found to be most suitable for the coupling
reaction among the screened organic solvents, and the forma-
tion of an equivalent amount of cyclopentane was detected in
the crude reaction mixture.
*To whom correspondence should be addressed. E-mail: chae.
yi@marquette.edu.
(1) Recent reviews: (a) Ritleng, V.; Sirlin, C.; Pfeffer, M. Chem. Rev.
2002, 102, 1731–1770. (b) Kakiuchi, F. In Topics in Organometallic
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2007; Vol. 24. (c) Chen, X.; Engle, K. M.; Wang, D.-H.; Yu, J.-Q. Angew.
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Yu, W.-Y.; Che, C.-M. J. Am. Chem. Soc. 2006, 128, 9048–9049.
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Soc. 2008, 130, 3266–3267.
The scope of the coupling reaction was explored by using
the catalyst 1 (Table 1). Both secondary and tertiary arylamides
were found to react smoothly with cyclic olefins to give the oxi-
dative coupling products predominantly. The secondary amides
with N-electron withdrawing group were found to promote the
oxidative coupling products 2 over the insertion products 3
(entries 7-9). Cyclic alkenes generally give the oxidative cou-
pling products 2 preferentially, but cyclohexene resulted in a low
yield of the coupling products (e15%). Steric and electronic
(5) Wang, D.-H.; Engle, K. M.; Shi, B.-F.; Yu, J.-Q. Science 2010,
327, 315–319.
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Tamura, M.; Kochi, T.; Sato, M.; Chatani, N.; Kakiuchi, F. J. Am. Chem.
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J. Am. Chem. Soc. 2008, 130, 9254–9256. (f) Tsuchikama, K.; Kasagawa,
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(8) See the Supporting Information for experimental details.
r
pubs.acs.org/Organometallics
Published on Web 10/21/2010
2010 American Chemical Society

Communication
Organometallics, Vol. 29, No. 22, 2010 5749
Table 1. Oxidative C-H Coupling Reaction of Arylamides and Aryl Ketones with Alkenesa
a Reaction conditions: carbonyl compound (0.5 mmol), alkene (2.5 mmol), 1 (15 mg, 5 mol %), CH2Cl2 (2 mL), 5 h. PhCl (2 mL) was used as the
solvent for temperatures >80 °C.
environments on the amide group were found to be less
important with 1,1-disubstituted and terminal olefins in yielding
a mixture of 2 and 3 for these cases (entries 12-19). In contrast,
the reaction with 1-hexene yielded a complex mixture of 2 and 3
that resulted from the coupling with both terminal and internal
olefins. The analogous coupling reaction of aryl ketones with
2-methylpropene yielded the 1,3-dimethylnaphthalene product 4
along with the insertion product 3 (entries 20-23). The forma-
tion of 4 can be readily rationalized by the chelate-directed
o-alkenylation followed by the dehydration and cyclization
sequence, in light of the recently disclosed dehydrative coupling
reaction of aryl ketones and cyclic alkenes.7b The salient feature
of the coupling reaction is that the regioselective o-C-H oxida-
tive olefination of arylamides has been achieved without em-
ploying any external oxidants or additives.
observed on the o-arene positions of both the coupling products
2e and 3e (55% D) and the amide substrate (39% D) as well as on
the unreacted cyclopentene (∼5% D). Such extensive o-H/D
exchange pattern on the amide substrate is consistent with a rapid
and reversible arene C-H bond activation step. In support of this
notion, a negligible isotope effect of kH/kD = 1.1 ( 0.1 was mea-
sured from the reaction of C6H5CONEt2 and C6D5CONEt2 with
cyclopentene at 80 °C (Figure S1, Supporting Information).
The following kinetic experiments were performed to gain
mechanistic insights into the coupling reaction. To examine the
H/D exchange pattern on the amide substrate, the treatment of
C6D5CONEt2 (0.5 mmol) and cyclopentene (2.5 mmol) in the
presence of 1 (5 mol %) in CH2Cl2 was monitored by NMR
(eq 2). At 50% conversion, extensive H/D exchange pattern was
To discern the rate-limiting step of the coupling reaction, the
carbon isotope effect of the coupling reaction was measured by

5750 Organometallics, Vol. 29, No. 22, 2010
Kwon et al.
employing Singleton’s NMR technique at natural abundance.9
The most pronounced carbon isotope effect was observed on the
ortho carbon when the 13C ratio of recovered C6H5CONEt2 at
80% conversion was compared to that of the virgin sample
(13C(recovered)/13C(virgin) at Cortho = 1.023, average of three
runs) (eq 3). This result indicates that the C-C bond formation
is the rate-limiting step of the coupling reaction.
Scheme 1. Proposed Mechanism of the C-H Oxidative Cou-
pling Reaction of Benzamide and Cyclopentene
In an effort to establish the nature of reactive species, the
naphthylamide-coordinated complex 5 was prepared from the
treatment of the tetranuclear complex [RuH(CO)(PCy3)]4(O)-
Rh(I)-olefin complexes were found to be active for the C-H
insertion of aryl ketones.13 In our case, the successful isolation of
6 further suggests that the coupling reaction could be inhibited
by the products. Indeed, the coupling reaction of N,N-diethyl-
benzamide and cyclopentene in the presence of 2.5 equiv of 2a
showed virtually no activity under otherwise similar conditions
as stipulated in eq 1 (e3% conversion).
(OH)2 with N,N-dimethyl-2-naphthamide and HBF4 OEt2.10
3
The subsequent treatment of 5 with cyclopentene (5 equiv) at
room temperature for 1 h resulted in the stable complex 6in 82%
yield (eq 4). The structure of 6 was elucidated by both solution
spectroscopic and X-ray crystallographic methods. The molec-
ular structure of 6 showed a square-pyramidal arrangement on
the metal center with Ru-H in an apical position. The complex
6 exhibited the same activity as the catalyst 1 toward the
coupling reaction of naphthylamide and cyclopentene.
The results provide a support for a mechanism involving
vinyl C-H bond activation as depicted in Scheme 1. We propose
that the initial arene exchange/π-coordination of an arylamide
from 1would form the arene-coordinated cationic Ru-H species
5, which further undergo chelate-directed o-C-H activation and
dehydrogenation to form the ortho-metalated species 7. The
subsequent vinyl C-H activation and the turnover-limiting aryl-
to-vinyl reductive elimination steps would form the cationic
Ru-H species 8. Both a carbon isotope effect study and the
successful isolation of the complex 6provide supporting evidence
for the rate-limiting C-C bond formation step and the involve-
ment of the cationic Ru-H complex 8. On the other hand, the
formation of the insertion product 3 can be readily explained by
invoking a direct olefin insertion and the subsequent o-C-H
activation and reductive elimination sequence from 5. One of the
major reasons the oxidative C-H coupling path is favored over
the Murai-type C-H insertion path may be due to the catalyst’s
ability to promote facile vinyl C-H activation. While the forma-
tion of metal-vinyl species has been well documented in the
C-H bond activation literature,14 its synthetic utility has been
rarely exploited in catalytic coupling reactions.
In summary, the cationic ruthenium hydride catalyst 1 was
found to be highly effective for the oxidative C-H coupling
reaction of arylamides with unactivated alkenes without em-
ploying any oxidizing agents. The preliminary kinetic and
spectroscopic studies suggest a mechanism involving rapid
o-arene and vinyl C-H activation and rate-limiting C-C bond
formation steps. Current effortsarebeingdirectedtoextendthe
synthetic utility as well as to elucidate a detailed mechanism of
the coupling reaction.
Complex 6 represents a rare example of a structurally
characterized cationic Ru-H species which is catalytically active
for chelate-assisted C-H activation reactions. Though ortho-
metalated complexes have been commonly invoked as the key
species for chelate-assisted C-H activation chemistry,1 structu-
rally well-characterized metalated ruthenium complexes were
often found to be catalytically inactive for the C-H insertion
reactions.11 More recently, Kakiuchi and Yu independently
reported the synthesis of catalytically active ortho-metalated
Ru and Pd complexes and their activity for both C-OandC-H
bond activation and insertion reactions of arene compounds,
respectively.12 It is also noteworthy that both Ru(0)-enone and
Acknowledgment. Financial support from the National
Institutes of Health, General Medical Sciences (No.
R15 GM55987), is gratefully acknowledged. We thank
Dr. Sergey Lindeman (Marquette University) for the
X-ray crystallographic determination of 6.
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Supporting Information Available: Text, figures, tables, and a
CIF file giving experimental procedures, spectroscopic data of
organic products, and X-ray crystallographic data for 6.Thismaterial
is available free of charge via the Internet at http://pubs.acs.org.
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metallics 2001, 20, 3745–3751. (b) Drouin, S. D.; Amoroso, D.; Yap,
G. P. A.; Fogg, D. E. Organometallics 2002, 21, 1042–1049.
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J. Am. Chem. Soc. 2010, 132, 686–693.
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