Mechanistic study of the oxidative coupling of styrene with 2-phenylpyridine derivatives catalyzed by cationic rhodium(III) via C-H activation

Article abstract of DOI:10.1021/ja401561q

The Rh(III)-catalyzed oxidative coupling of alkenes with arenes provides a greener alternative to the classical Heck reaction for the synthesis of arene-functionalized alkenes. The present mechanistic study gives insights for the rational development of this key transformation. The catalyst resting states and the rate law of the reaction have been identified. The reaction rate is solely dependent on the catalyst and alkene concentrations, and the turnover-limiting step is the migratory insertion of the alkene into a Rh-C(aryl) bond.

Full text of DOI:10.1021/ja401561q

Communication
pubs.acs.org/JACS
Mechanistic Study of the Oxidative Coupling of Styrene with
2‑Phenylpyridine Derivatives Catalyzed by Cationic Rhodium(III) via
C−H Activation
Mikael Brasse,†,‡,⊥ Juan Campora,† Jonathan A. Ellman,*,§ and Robert G. Bergman*,∥
́
̈
†Instituto de Investigaciones Químicas, Consejo Superior de Investigaciones Científicas-Universidad de Sevilla, c/Americo Vespucio
49, 41092 Sevilla, Spain
‡Department of Chemistry, University of California, Berkeley, California 94720, United States
§Department of Chemistry, Yale University, New Haven, Connecticut 06520, United States
∥Division of Chemical Sciences, Lawrence Berkeley National Laboratory, Berkeley, California 94720, United States
S
* Supporting Information
can be functionalized and identifying more convenient and
cost-effective stoichiometric oxidants.1a To improve these
ABSTRACT: The Rh(III)-catalyzed oxidative coupling of
alkenes with arenes provides a greener alternative to the
classical Heck reaction for the synthesis of arene-
functionalized alkenes. The present mechanistic study
gives insights for the rational development of this key
transformation. The catalyst resting states and the rate law
of the reaction have been identified. The reaction rate is
solely dependent on the catalyst and alkene concen-
trations, and the turnover-limiting step is the migratory
insertion of the alkene into a Rh−C(aryl) bond.
cross-couplings on a rational basis, it is crucial to understand
their mechanism. While arylations of different substrates with
cationic Rh(III) catalysts have been investigated,7 there are few
reports on the mechanism of oxidative reactions,8 none of
which include alkenes. Here we report a mechanistic study of
the coupling of 2-phenylpyridine with styrene catalyzed by
[Cp*RhCl2]2 (Cp* = C5Me5), activated by AgSbF6, and
employing a copper carboxylate as the oxidant. We also report a
kinetic study that identifies the resting states and the turnover-
limiting step for this transformation.
We chose 2-(4-fluorophenyl)pyridine (1) as a substrate
because it is known to form stable rhodacycles,9 and 4-
fluorostyrene (2) was selected because styrene derivatives are
known to be efficiently coupled by Rh(III).10 Fluorine
substitution at the para positions of both reagents provided a
convenient 19F NMR handle that allowed careful monitoring of
their concentrations during the reaction and the observation of
catalyst resting states. We previously reported the coupling of
aryl oximes with simple alkenes using a mixture of
[Cp*RhCl2]2 and AgSbF6 as the catalyst in tetrahydrofuran
(THF).6n We therefore tested the coupling of 1 with 2 under
the same conditions. Although Cu(OAc)2 gave excellent yields
as an oxidant, it exhibits low solubility in THF. This would
hamper NMR monitoring and make a kinetic study challenging.
To ensure the homogeneity of the reaction solutions, we
addressed this problem by using as the oxidant copper
heptanoate (4), which is fully soluble in THF. Employing 2
equiv of pyridine relative to styrene to avoid any overalkylation,
we recovered the expected coupling product 3 in 91% yield
(Scheme 2). An added benefit was that the solubility of 4
allowed us to reduce the amount of oxidant to 1 equiv, where
previously 2.1 equiv of Cu(OAc)2 was needed.
atalytic dehydrogenative cross-coupling reactions offer the
Cdesirable possibility of forming a new C−C bond directly
from two simple C−H bonds. Alongside the atom economy
advantage, this is fundamentally fascinating because a catalytic
system allows the coupling of two stable centers.1 In this regard,
the oxidative version of the Heck cross-coupling, also known as
the Fujiwara−Moritani reaction,2 is an interesting approach
that provides access to aryl-functionalized alkenes directly from
two C−H bonds without the need for prefunctionalized
partners (Scheme 1). This method is also of particular interest
for the prospective production of styrene directly from benzene
and ethylene.3
Scheme 1. The Fujiwara−Moritani (Oxidative Heck)
Reaction
A number of substrates have been oxidatively coupled to
alkenes using Pd(II) as a catalyst and various oxidants
[Cu(OAc)2, Ag2CO3, benzoquinone, etc.].1a,4 More recently,
Rh(III) complexes have proven to be efficient and versatile
catalysts for a variety of oxidative cross-couplings5 and
especially for the Fujiwara−Moritani reaction,6 even allowing
the coupling of simple unactivated alkenes.6n However, this
methodology could be made even more useful by broadening
the types of directing groups and the range of C−H bonds that
With this model in hand, our first objective was to gain
insight into the nature of the catalyst resting state or states and
their formation. It has been shown earlier that the C−H
activation of phenylpyridine by [Cp*RhCl2]2 leads to cyclo-
Received: February 26, 2013
© XXXX American Chemical Society
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Journal of the American Chemical Society
Communication
of the reaction mixture to those of synthesized samples, we
confirmed the formation of neutral carboxylate-ligated rhoda-
cycle 6 and cationic rhodacycle 7 (Scheme 4).
Scheme 2. Rh(III)-Catalyzed Oxidative Coupling of 2-(4-
Fluorophenyl)pyridine (1) and 4-Fluorostyrene (2)
a
Scheme 4. C−H Activation and Cyclometalation of 1
a
Conditions: 0.1 mmol of 1, 0.05 mmol of 2, 2.5 μmol of
[Cp*RhCl2]2, 0.01 mmol of AgSbF6, 0.05 mmol of Cu(O2C7H13)2
(4), 1 mL of THF, T = 50 °C, 12 h.
metalated Rh complexes that are either neutral when an acetate
salt is employed9b or cationic when AgSbF6 is used.7 In the
present case, the reaction mixture contained both AgSbF6 and
copper carboxylate salts. To distinguish cationic from neutral
rhodacycles under the operating conditions, we synthesized a
series of such complexes with different ligands (Scheme 3) and
We next utilized 19F NMR spectroscopy to monitor an actual
catalytic run with 6 as the precatalyst.12 Although 6 was the
predominant resting state, part of the rhodium was transformed
into a new species characterized by a set of two 19F resonances
at −108.5 and −110.0 ppm, and we reasoned that this species
was rhodacycle styrene adduct 11 (Scheme 5). When the
Scheme 3. Syntheses of Neutral and Cationic Rhodacycles
Scheme 5. Resting States during Oxidative Coupling
compared their 19F NMR chemical shifts. We observed that the
19F signals appear between −107 and −109 ppm for cationic
complexes 7−10 and at ca. −111 ppm for neutral complexes 5
and 6 in THF-d8.
We were also able to obtain single crystals useful for X-ray
diffraction analysis of complexes 5−7, 9, and 10. The solid-state
structures present the expected piano-stool geometry (Figure
1). The Rh−C distances are slightly longer for the cationic
a
The integration is not fully accurate because the NMR signals were
b
broad. Two rotamers.
temperature was increased, the signals of 6 and 11 became
broader, fading into the baseline at 65 °C. Upon cooling, the
signals became sharper again, and two rotamers of 11 could be
observed at 25 °C [see below and Figure S-2 in the Supporting
Information (SI)]. This fluxional behavior can be attributed to
ligand exchange between 6 and 11.
The independent synthesis and isolation of 11 from 2 and
[Cp*RhCl2]2 by addition of AgSbF6 proved to be difficult. We
1
observed the formation of a dark-violet species whose H and
19F NMR spectra were in agreement with the structure of 11,
but it decomposed rapidly into an undefined mixture of
products. However, in situ NMR monitoring of the addition of
2 to rhodacycle 7 in THF-d8 at −10 °C showed the clean
formation of 11 as a mixture of the syn and anti rotamers
(Scheme 6).
Figure 1. ORTEP views of complexes 5−7, 9, and 10. H atoms and
−
SbF6 counteranions have been omitted for clarity.
Scheme 6. Formation of the Rhodacycle Styrene Adduct
complexes, although the differences are small and within
experimental error: 5, 2.024(2) Å ≤ 6, 2.030(6) Å < 9,
2.042(4) Å ≤ 7, 2.046(7) Å < 10, 2.065(7) Å.11
We then carried out the stoichiometric cyclometalation of 1
by [Cp*RhCl2]2 and AgSbF6 in the presence of 4 (4:1:4:4
respectively) in THF. By comparing the 19F and 1H NMR data
B
dx.doi.org/10.1021/ja401561q | J. Am. Chem. Soc. XXXX, XXX, XXX−XXX

Journal of the American Chemical Society
Communication
By varying the temperature, we observed the reversible
interconversion of the rotamers due to free rotation of styrene
around the Rh−alkene bond (Figure S-3). This result
confirmed that 11 is indeed a π-olefin complex and not a
new metallacycle formed by styrene insertion into the Rh−C
bond. Although we were not able to observe the insertion
process, it is safe to assume that it takes place, leading to the
eventual formation of 3. This would be in agreement with the
work of Jones and co-workers, who showed that the reaction of
ethylene or propylene with Ir or Rh metallacycles leads to
unstable π-alkene complexes similar to 11 with iridium or to
insertion products with rhodium.13
From the above experiments, we concluded that 6 and 11 are
both resting states of the catalyst. These two species
interconvert through the exchange of the carboxylate anion
for styrene. This process is upstream from the migratory
insertion of styrene into the Rh−C bond. Since the ring-
expanded metallacycle could not be detected, it is reasonable to
assume that the ensuing steps leading to 3 are faster than the
alkene insertion, which determines the rate of the catalytic
reaction.
starting material followed first-order kinetics with a similar rate
for all silver concentrations (7.5−30 mol % relative to 2),
indicating a zeroth-order dependence on [Ag]. However, for
AgSbF6 concentrations lower than 20 mol %, the behavior
changed, and the styrene consumption deviated from first-order
behavior after 12 min (Figure S-8). We believe that this was
due to inadvertent catalyst decomposition, so in subsequent
reactions the silver concentration was kept at 20 mol %. First-
order behavior was reproducibly observed in these runs.
Monitoring the reactions under operating catalytic con-
ditions established that the concentrations of 6 and 11 hardly
varied during the course of the reaction. Assuming a steady-
state situation for 11 (eq 3) allows its concentration to be
expressed according to eq 4. Substitution of eq 4 into the rate
law (eq 2) furnishes eq 5, which expresses the rate as a function
of the concentrations of reactants 6 and 2. Using eq 5, we
obtained excellent fits with kobs = 2.72 min−1 for the
consumption of styrene 2 in catalytic runs with different
amounts of catalyst 6, showing that only the catalyst and
styrene concentrations are kinetically relevant.
d[3]
dt
This qualitative conclusion was tested by carrying out a
kinetic study designed to establish the rate law of the catalytic
transformation. We monitored the progress of the reaction by
19F NMR spectroscopy at 65 °C using 6 as the precatalyst and
an excess of 1 relative to 2. With a 10-fold excess of 1, the
reaction followed pseudo-first-order kinetics with k = 0.0269
min−1 for the consumption of 2 and a slightly lower rate (k =
0.024 min−1) for the formation of product 3 (Figure 2). The
= k2[11]
(2)
d[11]
dt
= k1[6][2] − k−1[11] − k2[11] = 0
(3)
k1[6][2]
[11] =
k−1 + k2
(4)
k1k2[6][2]
k−1 + k2
d[3]
dt
=
= kobs[6][2]
(5)
In Scheme 7 we depict a mechanism for this transformation
that is consistent with our qualitative observations and kinetic
results. The mixture of [Cp*RhCl2]2, AgSbF6, 1, and 4 gives
rise initially to resting state 6 through a C−H activation
mechanism of concerted metalation/deprotonation.14 Complex
6 is in equilibrium with 11 through exchange of styrene with
carboxylate. In the turnover-limiting step, the coordinated
styrene undergoes migratory insertion to give a new metalla-
cycle, probably stabilized by a carboxylate ligand similar to that
in 6. This new rhodacycle then undergoes β-elimination to
release the organic product 3 and a rhodium hydride complex
that upon elimination of carboxylic acid is reduced to Rh(I).
The latter is then reoxidized by copper to close the catalytic
cycle. This Rh(III/I) catalytic cycle involving the sequence C−
H activation, alkene insertion, β-elimination, and oxidation is in
agreement with previous reports on Rh(III) catalysis7,8 and
rhodacycle reactivity toward unsaturated molecules9a,13,15 and is
similar to that proposed for Pd(II/0).5a,16
Figure 2. Plots of the concentrations of substrate 2 and product 3 vs
time obtained by 19F NMR monitoring. Conditions: 0.5 mmol of 1,
0.05 mmol of 2, 5 μmol of 6, 0.01 mmol of AgSbF6, 0.05 mmol of 4,
0.7 mL of THF, 0.3 mL of THF-d8, 1 μL of C6F6 (as an internal
standard), T = 65 °C. Black dashed lines are fits using the equations
[2]t = [2]0e−kt (k = 0.0269 min−1) and [3]t = [2]0(1 − e−kt) (k = 0.024
min−1).
rate of consumption of 2 was the same (within experimental
error) when the original catalyst, 5% [Cp*RhCl2]2, was used
instead of 6, confirming that the same active species are
generated in both cases.
The order of each reactant was then determined by
measuring the reaction rates in the presence of variable excess
concentrations of 1, catalyst 6, AgSbF6, and 4 (Table S-1 in the
SI). The kinetic analysis showed a zeroth-order dependence on
4 and 1 and a first-order dependence on catalyst 6 (see the SI).
Interestingly, in early experiments the silver salt exhibited
apparently bimodal behavior. Initially, the consumption of the
In conclusion, by using a soluble copper carboxylate and
fluorine-substituted reactants that allowed monitoring by 19F
NMR spectroscopy, we were able to carry out a mechanistic
study and propose a catalytic cycle for the oxidative coupling of
styrene to phenylpyridine catalyzed by Rh(III). We hope that
the understanding provided for this transformation will
C
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Journal of the American Chemical Society
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(5) (a) Song, G.; Wang, F.; Li, X. Chem. Soc. Rev. 2012, 41, 3651.
(b) Patureau, F. W.; Wencel-Delord, J.; Glorius, F. Aldrichimica Acta
2012, 45, 31.
Scheme 7. Proposed Catalytic Cycle
(6) (a) Besset, T.; Kuhl, N.; Patureau, F. W.; Glorius, F. Chem.Eur.
J. 2011, 17, 7167. (b) Gong, T.-J.; Xiao, B.; Liu, Z.-J.; Wan, J.; Xu, J.;
Luo, D.-F.; Fu, Y.; Liu, L. Org. Lett. 2011, 13, 3235. (c) Li, X.; Gong,
X.; Zhao, M.; Song, G.; Deng, J.; Li, X. Org. Lett. 2011, 13, 5808.
(d) Park, S. H.; Kim, J. Y.; Chang, S. Org. Lett. 2011, 13, 2372.
(e) Patureau, F. W.; Glorius, F. J. Am. Chem. Soc. 2010, 132, 9982.
(f) Patureau, F. W.; Nimphius, C.; Glorius, F. Org. Lett. 2011, 13,
6346. (g) Satoh, T.; Miura, M. Chem.Eur. J. 2010, 16, 11212.
(h) Ueura, K.; Satoh, T.; Miura, M. Org. Lett. 2007, 9, 1407.
(i) Umeda, N.; Hirano, K.; Satoh, T.; Miura, M. J. Org. Chem. 2009,
74, 7094. (j) Wang, F.; Song, G.; Du, Z.; Li, X. J. Org. Chem. 2011, 76,
2926. (k) Wei, X.; Wang, F.; Song, G.; Du, Z.; Li, X. Org. Biomol.
Chem. 2012, 10, 5521. (l) Wencel-Delord, J.; Nimphius, C.; Patureau,
F. W.; Glorius, F. Chem.Asian J. 2012, 7, 1208. (m) Zhao, P.; Wang,
F.; Han, K.; Li, X. Org. Lett. 2012, 14, 3400. (n) Tsai, A. S.; Brasse, M.;
Bergman, R. G.; Ellman, J. A. Org. Lett. 2011, 13, 540. (o) Patureau, F.
W.; Besset, T.; Glorius, F. Angew. Chem., Int. Ed. 2011, 50, 1064.
(7) (a) Li, Y.; Zhang, X.-S.; Li, H.; Wang, W.-H.; Chen, K.; Li, B.-J.;
Shi, Z.-J. Chem. Sci. 2012, 3, 1634. (b) Tauchert, M. E.; Incarvito, C.
D.; Rheingold, A. L.; Bergman, R. G.; Ellman, J. A. J. Am. Chem. Soc.
2012, 134, 1482.
(8) Stuart, D.; Alsabeh, P.; Kuhn, M.; Fagnou, K. J. Am. Chem. Soc.
2010, 132, 18326.
(9) (a) Li, L.; Brennessel, W. W.; Jones, W. D. J. Am. Chem. Soc.
2008, 130, 12414. (b) Li, L.; Brennessel, W.; Jones, W. D.
Organometallics 2009, 28, 3492.
(10) Umeda, N.; Hirano, K.; Satoh, T.; Miura, M. J. Org. Chem. 2009,
74, 7094.
(11) Complexes 5−9 all served as active precursors for the catalytic
reaction. Only 10 was inactive because styrene could not displace the
PMe3 ligand.
(12) The same experiment was conducted using [Cp*RhCl2]2 as a
precatalyst, but several unidentified species were observed along with 6
and 11. Starting with 6 resulted in cleaner NMR spectra.
(13) Li, L.; Jiao, Y.; Brennessel, W.; Jones, W. D. Organometallics
2010, 29, 4593.
contribute to the development of other reactions involving the
direct coupling of two C−H bonds.
ASSOCIATED CONTENT
* Supporting Information
■
S
Experimental details for the synthesis and characterization;
kinetic experiments; NMR spectra for all compounds; and
crystallographic data for 5−7, 9, and 10. This material is
available free of charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
jonathan.ellman@yale.edu; rbergman@berkeley.edu
■
(14) Lapointe, D.; Fagnou, K. Chem. Lett. 2010, 39, 1118.
(15) Boutadla, Y.; Davies, D. L.; Al-Duaij, O.; Fawcett, J.; Jones, R.
C.; Singh, K. Dalton Trans. 2010, 39, 10447.
(16) Beccalli, E.; Broggini, G.; Martinelli, M.; Sottocornola, S. Chem.
Rev. 2007, 107, 5318.
Present Address
⊥M.B.: Cytec Industries, Inc., 1937 West Main Street,
Stamford, CT 06905, USA.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was supported by the NIH (Grant GM069559 to
J.A.E.); the Director, Office of Energy Research, Office of Basic
Energy Sciences, Chemical Sciences Division, U.S. Department
of Energy (Contract DE-AC02-05CH11231 to R.G.B.); the
Government of Spain (Project CTQ2009-11721 to J.C.); and
́
the Junta de Andalucia (Project FQM6276 to J.C.). M.B.
acknowledges the Seventh European Community Framework
Programme for a Marie Curie International Outgoing Fellow-
ship that supported this research and Dr. Michael Tauchert for
helpful discussions.
REFERENCES
■
(1) (a) Yeung, C. S.; Dong, V. M. Chem. Rev. 2011, 111, 1215.
(b) Liu, C.; Zhang, H.; Shi, W.; Lei, A. Chem. Rev. 2011, 111, 1780.
(2) Fujiwara, Y.; Moritani, I. Tetrahedron Lett. 1967, 8, 1119.
(3) Matsumoto, T.; Periana, R. A.; Taube, D. J.; Yoshida, H. J. Catal.
2002, 206, 272.
(4) Le Bras, J.; Muzart, J. Chem. Rev. 2011, 111, 1170.
D
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