Interplay of Experiment and Theory in Elucidating Mechanisms of Oxidation Reactions by a Nonheme RuIVO Complex

Article abstract of DOI:10.1021/jacs.5b04787

A comprehensive experimental and theoretical study of the reactivity patterns and reaction mechanisms in alkane hydroxylation, olefin epoxidation, cyclohexene oxidation, and sulfoxidation reactions by a mononuclear nonheme ruthenium(IV)-oxo complex, [Ru^IV(O)(terpy)(bpm)]²⁺ (1), has been conducted. In alkane hydroxylation (i.e., oxygen rebound vs oxygen non-rebound mechanisms), both the experimental and theoretical results show that the substrate radical formed via a rate-determining H atom abstraction of alkanes by 1 prefers dissociation over oxygen rebound and desaturation processes. In the oxidation of olefins by 1, the observations of a kinetic isotope effect (KIE) value of 1 and styrene oxide formation lead us to conclude that an epoxidation reaction via oxygen atom transfer (OAT) from the Ru^IVO complex to the C-C double bond is the dominant pathway. Density functional theory (DFT) calculations show that the epoxidation reaction is a two-step, two-spin-state process. In contrast, the oxidation of cyclohexene by 1 affords products derived from allylic C-H bond oxidation, with a high KIE value of 38(3). The preference for H atom abstraction over C-C double bond epoxidation in the oxidation of cyclohexene by 1 is elucidated by DFT calculations, which show that the energy barrier for C-H activation is 4.5 kcal mol^-1 lower than the energy barrier for epoxidation. In the oxidation of sulfides, sulfoxidation by the electrophilic Ru-oxo group of 1 occurs via a direct OAT mechanism, and DFT calculations show that this is a two-spin-state reaction in which the transition state is the lowest in the S = 0 state.

Full text of DOI:10.1021/jacs.5b04787

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Article
Interplay of Experiment and Theory in Elucidating Mechanisms
IV
of Oxidation Reactions by a Nonheme RuO Complex
Sunder N. Dhuri, Kyung-Bin Cho, Yong-Min Lee, Sun Young Shin,
Jin Hwa Kim, Debasish Mandal, Sason Shaik, and Wonwoo Nam
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.5b04787 • Publication Date (Web): 15 Jun 2015
Downloaded from http://pubs.acs.org on June 18, 2015
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Interplay of Experiment and Theory in Elucidating
Mechanisms of Oxidation Reactions by a Nonheme RuIVO
Complex
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Sunder N. Dhuri,†,‡,§ Kyung-Bin Cho,†,§ Yong-Min Lee,† Sun Young Shin,† Jin Hwa Kim,†
Debasish Mandal,¶ Sason Shaik,¶ Wonwoo Nam†,*
† Department of Chemistry and Nano Science, Ewha Womans University, Seoul 120-750, Korea
‡ Department of Chemistry, Goa University, Goa 403 206, India
¶ Institute of Chemistry and the Lise Meitner-Minerva Center for Computational Quantum Chemistry, The Hebrew
University of Jerusalem, 91904 Jerusalem, Israel
ABSTRACT: A comprehensive study on the reactivity patterns and reaction mechanisms in alkane hydroxylation, olefin
epoxidation, cyclohexene oxidation, and sulfoxidation reactions by a mononuclear nonheme ruthenium(IV)-oxo complex,
[RuIV(O)(terpy)(bpm)]2+ (1), has been conducted experimentally and theoretically. In alkane hydroxylation (i.e., oxygen
rebound versus oxygen non-rebound mechanisms), both the experimental and theoretical results show that the substrate
radical formed via a rate-determining hydrogen atom (H-atom) abstraction of alkanes by 1 prefers dissociation over
oxygen rebound and desaturation processes. In the oxidation of olefins by 1, the observations of the kinetic isotope effect
(KIE) value of 1 and the styrene oxide formation lead us to conclude that an epoxidation reaction via an oxygen atom
transfer (OAT) from the RuIVO complex to the C=C double bond is the dominant pathway. DFT calculations show that
the epoxidation reaction is a two-step two-spin state process. In contrast, the oxidation of cyclohexene by 1 affords
products derived from the allylic C-H bond oxidation, with a high KIE value of 38(3). The preference of the H-atom
abstraction over the C=C double bond epoxidation in the oxidation of cyclohexene by 1 is elucidated by DFT calculations,
in which the C-H activation energy barrier is 4.5 kcal mol-1 lower than the epoxidation energy barrier. In the oxidation of
sulfides, the sulfoxidation by the electrophilic Ru-oxo group of 1 occurs via a direct OAT mechanism, and DFT
calculations show that this is a two-spin state reaction where the transition state is the lowest in the S = 0 state.
INTRODUCTION
High-valent ruthenium-oxo complexes of heme and
nonheme ligands have also been invoked as active
oxidants in catalytic oxidation reactions.17-19 In heme
models, Ru-oxo porphyrin (Por) species have been shown
to perform C-H bond activation of alkanes, most likely by
(Por)RuVO species, which are the Ru analogues of the
CYP450 Compound I species.20–23 The oxidation reactions
of alkanes and olefins by nonheme Ru complexes have
long been known as well, wherein certain organic
products were formed selectively in high yields.24-47 Such
reactions are known to occur via H-atom abstraction,
hydride transfer, electron transfer, proton-coupled
electron transfer (PCET), or oxygen atom transfer (OAT)
mechanisms. For instance, oxidation of cumene by cis-
[RuIV(bpy)(py)(O)]2+ (bpy = 2,2′-bipyridyl, py = pyridine)
was first investigated several decades ago.25 It was initially
thought to occur through a hydride transfer mechanism,25
but it was later shown to occur through a H-atom
abstraction mechanism.35 One of the suggested pathways
High-valent metal-oxo complexes of heme and nonheme
ligands perform a wide range of biological oxidation
reactions, such as alkane hydroxylation, olefin
epoxidation, and sulfoxidation.1-10 The reactivities and
reaction mechanisms of the metal-oxo complexes have
been investigated intensively over the past several
decades due to their tremendous potential for industrial
and biomimetic uses. For example, a large number of
high-valent FeIVO complexes have been synthesized and
investigated in heme and nonheme systems, and their
chemical and reactivity properties have been well
established resulting from intensive mechanistic studies,
including as for the C-H bond activation reactions of
alkanes occurring via an hydrogen atom (H-atom)
abstraction (Scheme 1A), C-H bond activation or
epoxidation reactions of olefins (Schemes 1B and 1C), and
oxidation reactions of sulfides (Scheme 1C).11 -16
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proposed to occur through many pathways that
Scheme 1. Proposed Mechanisms in Alkane Hydroxyla-
tion, Cyclohexene Oxidation, and Oxygen Atom Trans-
fer Reactions by Metal-Oxo Species
ultimately accounted for the formation of different
organic products, kinetics, and spectra related to the
reactions. Other substrates were also used in the
mechanistic studies of RuIVO complexes.30,33-37
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Although tremendous efforts have been made to
elucidate the mechanism(s) of C-H bond activation of
RuIVO
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benzylic
and
allylic
C-H
bonds
by
species,24,28,29,31,32,34,35 theoretical studies have been
underused to decipher the distinct mechanistic steps of
bond activation by RuIVO. While there are some pure
theoretical works in Ru-oxo chemistry (e.g., using
(Por)RuVO species),22,23 combined experimental and
theoretical studies give a much more powerful insight
into reaction mechanisms, as shown by our earlier work
on the fundamental differences between two-state and
single-state reactivity patterns of FeIVO and RuIVO
complexes in the C-H bond activation reactions.48
Furthermore, combining experimental and theoretical
methods have enabled us to establish that the mechanism
of the C-H bond activation of hydrocarbons by metal-oxo
species in nonheme synthetic model reactions is different
from the oxygen rebound mechanism that has been well
established in heme enzymes and their models. In the
oxygen rebound mechanism, the H-atom abstraction
results in the formation of a carbon radical and a metal-
hydroxo complex (Scheme 1A, pathway a), followed by the
rebound of the carbon radical to the metal-hydroxo that
results in producing alcohol or desaturated products
(Scheme 1A, pathways b, c, and d).49-53 However, in the
case of a dissociative oxygen non-rebound reaction, the
substrate radical escapes from the cage and then reacts
with a second metal-oxo molecule to give hydroxylated
products (Scheme 1A, pathways e and f for alkane
hydroxylation; Scheme 1B, pathways j and k for allylic C-H
bond activation).54-59 We have shown recently that this
radical dissociative mechanism prevails in C-H bond
activation reactions by FeIVO, MnIVO, CrIVO, and FeVO
catalysts in nonheme systems.54-59 Very recently, we have
also shown that an interplay of tunneling and spin
inversion probability has to be taken into account in
included a cumyl radical reacting with a second RuIVO
species (Scheme 1A, pathways a, e, and f). As multiple
organic products were seen in this reaction, as well as RuII
products, it was concluded that this pathway acts parallel
to oxygen rebound and desaturation type reactions done
by RuIIIOH (Scheme 1A, pathways b, d, and e), followed by
more downstream reactions in the pathway to the final
products. A second example, also using cumene as a
substrate but with different catalyst ligands, resulted in
experimental observation of RuIIIOH and RuIII-alkoxo
species, described as intermediates of a rebound process
(Scheme 1A, pathways a, b, and c).45 A third example is
the oxidation of cyclohexene and indene, which was
likewise shown to occur through an initial C-H bond
activation pathway rather than an epoxidation pathway
(Scheme 1B, pathways g versus h).32 The reactions were
Figure 1. Chemical structure (left) and DFT-optimized struc-
ture (right) of complex 1, optimized at B3LYP/LACVP level.
Atom colors: = Ru, = O, = N, = C, and
= H.
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oxidation of styrene and thioanisole by 1 occurs via an
OAT mechanism, we show that the oxidation of
cyclohexene by 1 affords products resulted from a C-H
bond activation reaction rather than an epoxidation
reaction. All the results obtained experimentally in this
study are replicated in silico by theoretical calculations,
detailing the precise steps involved in the oxidation
reactions.
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RESULTS AND DISCUSSION
Generation and Characterization of 1. The
ruthenium(IV)-oxo complex 1 was synthesized by reacting
[RuII(terpy)(bpm)(H2O)](ClO4)2 with PhIO in CH3CN at
25 oC.60 Upon addition of PhIO (1.2 equiv, dissolved in
MeOH) to
a
solution containing the starting RuII
complex, the UV-vis band at 485 nm decayed within 2
min with the concurrent appearance of a new peak at 445
nm (ε = 2000 M–1 cm–1) (Figure 2a). The yellowish orange
o
species 1, which was metastable at 25 C (t1/2 ~1 h), was
characterized by various spectroscopic methods. The
electrospray ionization mass spectrum (ESI-MS) of 1
exhibited prominent mass peaks at m/z = 254.6 and
608.0, whose mass and isotope distribution patterns
correspond to [RuIV(O)(terpy)(bpm)]2+ (calc. m/z = 254.5)
and [RuIV(O)(terpy)(bpm)(ClO4)]+ (calc. m/z = 608.0),
respectively (Figure 2b). When 1 was generated with
isotopically labeled PhI18O, the mass peak at m/z = 608.0
due to 1-16O shifted to m/z = 610.0 due to 1-18O, indicating
that 1 contains one oxygen atom. The resonance Raman
(rRaman) spectrum of 1 exhibited a vibration at 798 cm–1,
which shifted to 757 cm–1 upon introduction of 18O (Figure
2c). The observed isotopic shift of ΔQ = 41 cm–1 upon 18O-
substitution is in a good agreement with the calculated
value of ΔQ = 41 cm–1 for the Ru-O diatomic vibration, as
reported for other Ru(IV)-oxo species.19,43,45 It is also in
agreement with our DFT calculated Ru-O vibration
frequency, which was found to be at 796 cm–1 and shifted
to 758 cm–1 upon 18O substitution. The X-band electron
paramagnetic resonance (EPR) spectrum of 1 was silent,
consistent with 1 being an integer spin system. The spin
Figure 2. (a) UV-vis spectra of [Ru(terpy)(bpm)(H2O)]2+
(0.25 mM, black line) and 1 (0.25 mM, red line) in CH3CN at
25 oC. Inset shows the time course monitored at 485 nm due
to the decay of [Ru(terpy)(bpm)(H2O)]2+. (b) ESI-MS of 1.
1
state of 1 was then determined using H NMR technique
Peaks at m/z
=
254.6 and 608.0 correspond to
254.5) and
of Evans;61,62 a magnetic moment of 3.3 B.M. at –20 oC
indicates that 1 is an intermediate-spin (S = 1) RuIV(O)
complex (see Experimental Section; see also Supporting
[RuIV(O)(terpy)(bpm)]2+ (calc. m/z
=
[RuIV(O)(terpy)(bpm)(ClO4)]+ (calc. m/z = 608.0), respec-
tively. Insets show the observed isotope distribution patterns
for 1-16O at m/z = 608.0 (left panel) and 1-18O at m/z = 610.0
(right panel). (c) Resonance Raman spectra of 1-16O (black
line) and 1-18O (blue line) in CH3CN recorded with 406.7-nm
1
Information (SI), Figure S1 for H NMR spectrum of 1).
DFT calculations confirmed that the lowest spin state was
the S = 1 state, 14.1 and 60.3 kcal mol-1 (in Gibb’s free
energy, ΔG) lower than the S = 0 and S = 2 states,
respectively (SI, Table S1). The high energy of the S = 2
modeling this kind of C-H activation reactions.59
Herein, we provide results obtained from combined
experimental and theoretical studies that strongly
support that the C-H bond activation of alkanes by a
2
state is due to high lying σ*xy and σ*z orbitals, effectively
ruling out any reactions associated with participation of
these orbitals. Taken together, the spectroscopic and
computational data clearly demonstrate that 1 is an S = 1
[RuIV(O)(terpy)(bpm)]2+ complex (Figure 1).
mononuclear
nonheme
RuIVO
complex,
[RuIV(O)(terpy)(bpm)]2+ (1, terpy = 2,2′:6′,2′′-terpyridine,
bpm = 2,2′-bipyrimidine; see Figure 1 for DFT-optimized
structure), follows a dissociative oxygen non-rebound
mechanism (Scheme 1A, reaction pathway e). While the
C-H Bond Activation Reaction by 1. We carried out the
C-H bond activation reactions using substrates with bond
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second-order rate constant (k2) of 5.0 × 10–1 M–1 s–1 (Figure
3b). Similarly, when we used deuterated ethylbenzene-d10
as a substrate, a second-order rate constant (k2) of 2.3 ×
10-2 M-1 s-1 was obtained. Thus, a kinetic isotope effect
(KIE) value of 22(2) was obtained in the oxidation of
o
ethylbenzene versus ethylbenzene-d10 in CH3CN at 25 C
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(Figure 3b). Second order rate constants for other alkanes
were determined similarly (SI, Figure S2), and Figure 3c
shows a good linear correlation between the logarithm of
k2′ and the C-H BDEs of the substrates. On the basis of
the large KIE value and the good correlation between the
logarithms of k2′ and the substrate BDE values, we
conclude that the C-H bond activation of alkanes by 1
occurs via a H-atom abstraction from substrate C-H
bonds as the rate-determining step (r.d.s.) (Scheme 1A,
pathway a).32,35
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Product analysis of the reaction solution of 1 and
ethylbenzene revealed the formations of 1-phenylethanol
(27(4)%), acetophenone (8(3)%), and styrene (2(1)%)
under Ar atmosphere. The total product yield of 45%,
calculated accounting for the fact that acetophenone is a
4-e– oxidation product, suggests that one molecule of
substrate was oxidized by two molecules of RuIVO (vide
infra). When the ethylbenzene oxidation was performed
by 1-18O, the 1-phenylethanol product was found to
contain 71(5)% of 18O (SI, Figure S3), demonstrating that
the source of oxygen in the 1-phenylethanol product was
1-18O. When the reaction was carried out in the presence
of air, the yields of 1-phenylethanol, acetophenone, and
styrene were 16(4), 30(3), and 8(3)%, respectively. In
addition, when the oxidation reaction of ethylbenzene by
1 was performed in the presence of CCl3Br (500 equiv)
under Ar atmosphere, 1-bromoethylbenzene was obtained
as the sole product.54
We also characterized the Ru product formed in the
reaction of 1 and ethylbenzene by EPR and ESI-MS. The
X-band EPR spectrum of the Ru product showed signals
with g = 2.42, g = 2.16, and g = 1.91, indicating the
oxidation state of +3 for the Ru product (SI, Figure S4a).45
The ESI-MS of the solution exhibited a prominent mass
peak at m/z = 255.1, whose mass and isotope distribution
pattern correspond to [RuIII(terpy)(bpm)(OH)]+ (calc. m/z
= 255.0) (SI, Figure S4b). Further, addition of 1 equiv of
1,1′-dimethylferrocene (Me2Fc) to the complete reaction
solution of 1 and ethylbenzene resulted in the formation
of RuII and 1,1′-dimethylferrocenium ion (Me2Fc+) with
>90% yield (SI, Figure S5a), indicating that the RuIII
species produced was reduced to RuII by Me2Fc (see also
SI, Figure S5b for ESI-MS). Thus, all the results discussed
above strongly support that RuIII-OH species, not RuII
species, was formed in the reaction of ethylbenzene by 1.
Figure 3. (a) UV-vis spectral changes observed in the reac-
tion of 1 (0.25 mM, red line) and ethylbenzene (5.0 mM) in
o
CH3CN at 25 C. Inset shows the time course monitored at
460 nm. (b) Plots of pseudo-first-order rate constants, kobs (s-
1), against concentrations of ethylbenzene-h10 (black circles)
and ethylbenzene-d10 (red circles) to determine second-order
o
rate constants (k2) in CH3CN at 25 C. (c) Plot of log k2′ ver-
sus C-H BDEs of substrates. The k2’ values are obtained by
dividing second-order rate constants (k2) by the number of
i
l
t t
t C H b d i th
b t t
dissociation energies (BDEs) between 81.0 kcal mol-1
(triphenylmethane) and 95.5 kcal mol-1 (cyclooctane) in
CH3CN at 25 C. Upon addition of ethylbenzene to the
0
solution of 1, the UV-vis peak at 445 nm was slowly
converted to a new peak at 460 nm with clean isobestic
points at 337, 363, and 628 nm (Figure 3a). The first-order
rate constants (kobs), determined by pseudo-first-order
fitting of the kinetic data for the formation at 460 nm,
increased proportionally with the increase of
ethylbenzene concentration, leading us to determine a
The observations described above are contrary to the
oxygen rebound mechanism, since the hydroxylation of
alkanes by RuIVO species should yield RuII species as a 2e–
reduced product in the oxygen rebound mechanism.34,35,45
Since we could not rule out a possibility that the RuIII
formation resulted from comproportionation of RuIV(O)
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Figure 4. Reaction energy profile of the ethylbenzene C-H activation reaction by 1 at 25 oC. The initial HAT reaction in the S = 1
state creates a substrate intermediate 3IE, where the reaction has a number of choices (see text), including spin flipping (marked
with a loop in the center of the graph) with an estimated minimum energy barrier of 5.0 kcal mol-1. The lowest energy pathway is
therefore the S = 1 dissociation pathway where the product state (3PEx+RuOH) is only 0.20 kcal mol-1 above the separated reactants,
3RE+RuO
.
and RuII species, we carried out a control reaction by
reacting equal amounts of 1 and [RuII(terpy)(bpm)]2+. In
this reaction, no formation of RuIII species was observed
in UV-vis, EPR, and ESI-MS (SI, Figure S6), leading us to
conclude that the RuIII-OH species was formed exclusively
from the H-atom abstraction reaction of alkanes by 1, but
not from the comproportionation of RuIV(O) and RuII
species.
Then, how is the RuIII-OH species formed in the C-H
bond activation of alkanes by 1? We propose that after
RuIII-OH and alkyl radical species are formed in the first
step of the C-H bond activation by 1 (Scheme 1A, pathway
a), the dissociation process is the preferred pathway
(Scheme 1A, pathway e), rather than the oxygen rebound
(Scheme 1A, pathways b and c) and desaturation (Scheme
1A, pathway d) processes. This conclusion is reached
based on the results of the organic products formed in the
presence of O2 (i.e., the substrate radical dissociation
from RuIIIOH and reaction with O2 to give hydroxylated
prodcuts) and in the presence of CCl3Br (i.e., the substrate
radical dissociation from RuIIIOH and reaction with
CCl3Br to give brominated product) as well as the
presence of the RuIII product. These results are in line
with our earlier results reported in the reactions of
nonheme FeIVO, MnIVO, CrIVO, and FeVO complexes.54-59
multiplicity M = 2S + 1 per convention), relative to the
sum of the energies of the separated reactants (3RE+RuO, as
opposed to the reactant complex, 3RCE). This step was
found to be the r.d.s. (Scheme 1A, pathway a), comparable
to the experimentally determined barrier of 18.3 kcal mol-1
(obtained by converting k2’ through the Eyring equation).
A two-spin state reaction was ruled out at this step of the
1
reaction as the S = 0 state TSE was high in energy (22.5
kcal mol-1). Hence, after the initial H-atom abstraction
step, the resulting RuIIIOH species is in S = 1/2 state, while
the substrate has an D-radical, in total making it an S = 1
state (3IE). In the second step, the reaction has four
pathway choices; i) the rebound reaction (Scheme 1A,
pathways b and c), ii) abstracting another H-atom from
the substrate to perform a desaturation reaction (Scheme
1A, pathway d), iii) dissociating (Scheme 1A, pathway e),
or iv) changing the D-spin of the substrate to a E-spin and
performing
the
rebound/desaturation/dissociation
reaction on the S = 0 spin state surface. The first two
choices (i and ii) are ruled out as their transition states,
3TSE-reb and 3TSE-des, were found to be at 28.4 and 27.8 kcal
mol-1 above the reactants, respectively. The dissociation
option (iii) is then much more preferable with an
exothermic dissociation energy of 1.3 kcal mol-1 (i.e., the
3
dissociated products PEx+RuOH are 0.20 kcal mol-1 above
3RE+RuO).
To support the dissociation hypothesis, we performed
DFT calculations for the reaction of 1 and ethylbenzene
(SI, Tables S2, S7, and S12). The DFT calculations resulted
in a reaction barrier of 15.3 kcal mol-1 for the S = 1 state
(3TSE, Figure 4, the left superscript refers to the
1
The spin flip option (iv) to reach IE is in principle
possible. As the S = 0 rebound (1TSE-reb) and desaturation
(1TSE-des) transition states are very low (3.1 and 4.2 kcal
mol-1, respectively) and the spin orbit coupling on Ru is
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kcal mol-1 and 1.0 kcal mol-1, respectively (Table S2).
Without these effects, the KIE value would have been 7,
using the free energies. With tunneling, the KIE value is
now 25, which is close to the experimental value of 22(2).
Epoxidation of Styrene by 1. We investigated the olefin
oxidation using styrene-h8 and styrene-d8 as substrates.
Upon addition of styrene to the solution of 1 in CH3CN at
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o
25 C, 1 decayed with the formation of a new peak at 450
nm (Figure 5a). The first-order rate constants (kobs),
determined by pseudo-first-order fitting of the kinetic
data at 450 nm, increased proportionally with the
increase of substrate concentrations, affording the
second-order rate constants of 1.6 × 10-1 M-1 s-1 for both the
reactions of styrene and styrene-d8 (Figure 5b). The KIE
value of 1 suggests that the reaction of 1 with the olefins
does not occur via an H-atom abstraction pathway, but
via an OAT to the C=C double bond (Scheme 1C). Indeed,
styrene oxide (84(5)%) was formed as the major product
with the formation of
a
small amount of 2-
phenylacetaldehyde (4(1)%) under Ar atmosphere. In the
reaction where 1-18O was used, the styrene oxide product
contained 78(4)% of 18O (SI, Figure S9), suggesting that
the oxygen in the styrene oxide product derived from the
RuIVO species. The characterization of the Ru product
formed in the epxodation reaction was also carried out
using EPR and ESI-MS. The EPR spectrum was silent,
suggesting the formation of RuII species as the end
product. The ESI-MS data exhibited mass peaks
corresponding to [RuII(terpy)(bpm)(CH3CN)]2+ (SI, Figure
S7; also see SI, Figure S8 for the conversion of the peak at
485 nm due to [RuII(terpy)(bpm)(H2O)]2+ to the peak at
450 nm due to [RuII(terpy)(bpm)(CH3CN)]2+). Based on
the product analysis of the reaction solution of 1 and
styrene, we conclude that styrene was oxidized to styrene
oxide with the conversion of 1 to RuII species (Scheme 1C).
Figure 5. (a) UV-vis spectral changes observed in the reac-
tion of 1 (0.25 mM, red line) and styrene (13 mM) in CH3CN
o
at 25 C. Inset shows the time course monitored at 450 nm.
(b) Plots of pseudo-first-order rate constants, kobs (s-1),
against concentrations of styrene-h8 (black circles) and sty-
rene-d8 (red circles) to determine second-order rate con-
stants, k2, and KIE value in CH3CN at 25 oC.
large, this pathway would seem to be competitive with
the S = 1 dissociation reaction. However, a spontaneous
spin flip of a carbon-centered radical is not necessarily an
ultra-fast process. We have previously argued that, even if
we assume an ultra-fast spin flip process of 109 s-1, this
would still be equivalent to having an energy barrier of 5.0
kcal mol-1 according to the Eyring equation at room
temperature.56 This would not be competitive with the
dissociation energy of 1.3 kcal mol-1. Even if the spin flip
occurs, however, the dissociation energy at the S = 0 state
is still exothermic by 1.2 kcal mol-1. Hence, the
dissociation mechanism will likely be preferred anyhow,
which is more in line with our experimental results
showing 45% yield of products compared to the projected
50% product yield in the dissociative mechanism.54-59
DFT calculations (SI, Tables S3, S8, and S13) reveal that,
in the S = 1 state, this reaction would have been a two-
step process (Figure 6). In the first step, 1 attacks the
terminal C-atom to form a Ru-O-C bonded intermediate
3IS, over a transition state at 14.4 kcal mol-1 (3TS1S). The
alternative of attacking the other C-atom in the ethane
group has a higher transition state at 22.8 kcal mol-1 (not
shown). The second step involves closing the epoxide
ring. However, it is found that this step goes over a
3
transition state TS2S at 31.6 kcal mol-1, to a RuII product
An additional issue in this reaction is the tunneling, as
indicated by the high experimental KIE. Using Eckart
tunneling,63 we found that tunneling effect corresponds to
lowering the S = 1 ethylbenzene-h10 and –d10 barriers by 1.8
that is at 22.4 kcal mol-1 (3PS). Hence, with the high barrier
and an endothermic reaction energy, the reaction at the S
= 1 surface seems less probable.
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In the S = 0 state, the epoxidation reaction features a
1
one-step process over a single transition state TSS at 22.6
kcal mol-1. This energy barrier is on the high side,
3
especially compared to TS1S (14.4 kcal mol-1) and also the
experimental value (k2 corresponding to 18.5 kcal mol-1),
3
but it is lower than TS2S (31.6 kcal mol-1). Moreover, the
1
3
RuII product PS is 34.5 kcal mol-1 more preferred than Ps.
It is, in fact, a well known experimental fact that RuII is an
S = 0 species. Thus, it is clear that a spin state flip to S = 0
has to occur somewhere along the reaction pathway.
Based on our calculated data, we propose that this occurs
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at 3IS. In this way, the reaction can utilize the low TS1S to
3
perform half of the reaction. Then, a spin flip will allow
the reaction to bypass the high 3TS2S, and close the
epoxide ring. Indeed, we found a minimum energy
crossing point (MECP) between these two states at 2.5
kcal mol-1 in electronic energy (ΔE), where optimization
Figure 6. Reaction energy profile of the styrene epoxidation
o
by 1 at 25 C. The S = 1 surface features a two-step reaction
3
mechanism, whereas the S = 0 surface shows a concerted
one-step mechanism. A change in spin state is proposed after
the 3IS step, marked with an arrow.
from this geometry with S = 1 led to IS, and with S = 0 to
1Ps. While we cannot calculate the final ΔG for the MECP
(which would be dependent on, among other things,
thermal contributions and spin inversion probabilities),
assuming that the corrections to the electronic energy is
less than 10 kcal mol-1, the rate-limiting barrier is 3TS1S.
value of 38(3) (Figure 7).32,34 Further, activation
parameters, entalpy (ΔH‡) and entropy (ΔS‡), determined
in the reactions of
1
with cyclohexene-h10 and
C-H Bond Activation versus Epoxidation in the
Oxidation of Cyclohexene by 1. We then investigated
the reaction of 1 with cyclohexene-h10 and cyclohexene-d10
cyclohexene-d10 were different depending on the
substrates (SI, Figure S11a), whereas the reactions of 1 with
styrene-h8 and styrene-d8 showed that the enthalpy and
entropy values were the same irrespective of the
substrates (i.e., styrene and deuterated styrene; SI, Figure
S11b). The results regarding KIE and activation parameters
indicate that the oxidation of cyclohexene by 1 occurs via
a C-H bond activation reaction including tunneling.
Based on observations of the good BDE correlation with
log k2’ (Figure 3c) and the large KIE value (Figure 7), we
conclude that an H-atom abstraction in the allylic α-C-H
bond activation of cyclohexene by 1 is the r.d.s. (Scheme
1B, pathway g), which is different from the C=C double
bond epoxidation of styrene (Scheme 1C).
o
in CH3CN at 25 C. Upon addition of cyclohexene to the
solution of 1, we observed the formation of a new peak at
460 nm (SI, Figure S10); the spectral change was similar to
that observed in the C-H bond activation of ethylbenzene
by 1 (Figure 3a). A second-order rate constant of k2
=
4.2(4) M-1 s-1 was determined, and a k2’ value was obtained
by dividing the second-order rate constant (k2) with the
number of equivalent target C-H bonds in cyclohexene
(e.g., k2’ = k2/4). The log k2’ of this reaction fits well into
the line in Figure 3c, implying that the oxidation of
cyclohexene by 1 occurs via a C-H bond activation
process. When cyclohexene-d10 was used as a substrate, k2
= 1.1(1) × 10-1 M-1 s-1 was obtained, thus giving a large KIE
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Figure 7. Plots of the pseudo-first-order rate constants, kobs
(s-1), against concentrations of cyclohexene-h10 (black circles)
and cyclohexene-d10 (red circles) to determine second-order
Figure 8. Epoxidation versus C-H bond activation reaction
When we carried out product analysis in the
cyclohexene oxidation by 1 under Ar atmosphere, 26(3)%
of cyclohex-2-enol and 8(2)% of cyclohex-2-enone, in
total 42% (26 + 8 × 2%) yield, were obtained as products
(Table 1). No formation of cyclohexene oxide product was
observed in this reaction. Cyclohex-2-enol formed in the
cyclohexene oxidation by 1-18O contained 82(4)% of 18O
(SI, Figure S12), showing that the source of oxygen in the
product was 1. The decayed Ru product in the reaction of 1
and cyclohexene was determined to be RuIII-OH species
by analyzing the reaction solution with ESI-MS and EPR
spectroscopies and by carrying out a reaction with Me2Fc;
the Ru product was the same as that obtained in the
ethylbenzene oxidation by 1 (SI, Figures S4 – S6).
Interestingly, when we used cyclohexene-d10, a small
amount of cyclohexene oxide (7(2)%) was obtained along
with cyclohex-2-enol (21(2)%) and cyclohex-2-enone
(9(3)%).59 Taken altogether, the experimental results
demonstrate that a H-atom abstraction by 1 is the r.d.s.
(Scheme 1B, pathway g) and the oxygen non-rebound
mechanism takes place (Scheme 1B, pathways j and k); the
reaction mechanism is identical to that proposed in the
oxidation of ethylbenzene by 1.
energy profile for the cyclohexene oxidation reactions by 1 at
o
25 C, showing only the first steps of the reactions. Starting
from the middle of the graph, the C-H bond activation reac-
tion goes in the right direction over a minimum barrier of
14.6 kcal mol-1. Epoxidation, going to the left, has a higher
minimum barrier of 19.1 kcal mol-1. The entire shape of the
potential energy surface is similar to those for ethylbenzene
for C-H bond activation (Figure 4) and styrene for epoxida-
3TSC-HAT at 14.6 kcal mol-1 (to be compared with the
experimental value of 17.4 kcal mol-1 converted from k2’)
and 1TSC-HAT at 21.5 kcal mol-1 (Figure 8). The oxygen non-
rebound pathway is here indeed preferred as well, with
energies at -3.85 / 28.0 / 24.8 kcal mol-1 (3PC•+RuOH / 3TSC-reb
/
3TSC-des, respectively). Again, the S = 0 second step
barriers are low, but the same arguments against spin
inversion here apply as in the ethylbenzene case (vide
supra). Likewise, the energetic profile of cyclohexene
epoxidation is similar to the styrene epoxidation
described above. The S = 1 epoxidation occurs in a two-
step process, whereas the S = 0 surface contains one TS
3
1
(3TS1C-OAT / TS2C-OAT / TSC-OAT at 19.1 / 33.0 / 24.9 kcal
mol-1, respectively). Thus, spin inversion likely occurs here
at IC-OAT as well. However, since TS1C-OAT (19.1 kcal mol-1)
3
3
is 4.5 kcal mol-1 higher than TSC-HAT (14.6 kcal mol-1), the
3
DFT calculations (SI, Tables S4, S9, and S14) show that
the H-atom abstraction of cyclohexene is the r.d.s with.
H-atom abstraction reaction takes precedence over the
OAT reaction, in agreement with experiments. Upon
deuteration, this difference is reduced to 2.6 kcal mol-1,
making partial epoxidation possible. The KIE values here
are again more in agreement with the experimental value
of 38 when including tunneling effects (using Eckart
tunneling: KIE = 24), compared to without tunneling (KIE
= 6).
Table 1. Oxidation Products of Cyclohexene-h10 and
Cyclohexene-d10 by 1a
substrate
product
yield (%)
26(3)
8(2)
cyclohexene-h10
cyclohex-2-enol
cyclohex-2-enone
cyclohexene oxide
cyclohex-2-enol
cyclohex-2-enone
cyclohexene oxide
Sulfoxidation by 1. Finally, we investigated the oxidation
of sulfides by 1. Upon addition of thioanisole to the
trace
21(2)
9(3)
o
CH3CN solution of 1 at -40 C, the intermediate decayed
cyclohexene-d10
with the appearance of a peak at 485 nm (SI, Figure S13).
The pseudo-first-order rate constant increased linearly
with the increase of thioanisole concentration to give a
second-order rate constant of k2 = 3.1(4) M-1 s-1 (Figure 9a).
When para-X-substituted thioanisoles (X = OMe, Me, H,
Br, and CN) were used in the sulfoxidation reaction, a ρ
7(2)
a
Reaction conditions: Reactions were run with 1 (1.0
mM) and substrates (50 mM) under Ar atmosphere in
o
CH CN at 25 C See experimental section for product
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Figure 10. Reaction energy profile for the sulfoxidation reac-
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tion of thioanisole by 1 at –40 C. A spin state change is pre-
1
1
dicted to occur near TST so that the low energy TST can be
utilized, which is consistent with the fast experimental rates
observed in this reaction.
is in play here, where the reaction switches to the S = 0
surface to utilize the low-lying 1TST. In fact, an MECP was
found just after 1TST at ΔE = 14.5 kcal mol-1, where
3
geometry optimization on one side resulted in RCT and
Figure 9. (a) Plot of pseudo-first-order rate constants, kobs (s-
on the other side in 1PT.
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1), against thioanisole concentration to determine a second-
order rate constant in the reaction of 1 and thioansiole in
CH3CN at –40 C. (b) Hammett plot of log k2 against σp of
para-X-substituted thioanisole derivatives (X = OMe, Me, H,
CONCLUSION
o
+
In summary, the C-H bond activation, epoxidation, and
sulfoxidation reactions by mononuclear nonheme RuIVO
complexes have been investigated over the past three
decades;24-48 however, some of the proposed mechanisms
in the oxidation reactions are still controversial and
remain elusive, especially in the C-H bond activation
reactions of alkanes and olefins containing allylic C-H
bonds. Moreover, we have shown recently that
mononuclear nonheme metal-oxo complexes conduct the
C-H bond activation reactions via an oxygen non-rebound
mechanism, not via a conventional oxygen rebound
mechanism.54-59 We therefore reinvestigated the
mechanisms of the alkane hydroxylation, C-H bond
activation versus olefin epoxidation in cyclohexene
oxidation, and oxygen atom transfer reactions with a
spectroscopically well-characterized RuIVO complex,
[RuIV(O)(terpy)(bpm)]2+, using both experimental and
theoretical methods. In the alkane hydroxylation, both
the experimental and theoretical results demonstrate
unambiguously that the dissociation of the substrate
radical formed via a rate-determining H-atom abstraction
of alkane C-H bonds is more favorable than the oxygen
rebound and desaturation processes. In the oxidation of
olefins containing allylic C-H bonds, the experimental
results show the preference on the H-atom abstraction
over the C=C double bond epoxidation in the oxidation of
cyclohexene by 1 and are further supported by DFT
calculations, in which the energy barrier for the C-H
activation barrier is indeed lower than the epoxidation
energy barrier. In contrast, olefins without the allylic C-H
value of –2.1 was obtained from the Hammett plot of log
+
k2 against σp (Figure 9b; SI, Figure S14). This result
indicates that the Ru-oxo group of 1 possesses an
electrophilic character. In addition, when the rate
constants were plotted against the oxidation potential
(Eox) of thioanisole derivatives, we observed a good linear
correlation with a slope of –6.1 (SI, Figure S15), suggesting
that the oxidation of thioanisoles by 1 occurs via a direct
OAT mechanism (Scheme 1C, pathway m), as proposed in
the oxidation of PPh3 or PEt3 by other RuIVO species.48,64
Product analysis of the reaction solution revealed that
methyl phenyl sulfoxide was formed as a sole product
(85(5)% yield based on the amount of 1 used). When the
thioanisole oxidation was performed by 1-18O, the methyl
phenyl sulfoxide product contained 70(5)% of 18O,
indicating that the source of the oxygen atom in the
sulfoxide product was 1 (SI, Figure S16a). Based on the
analysis of the reaction solution using EPR (not shown,
but a silent EPR spectrum) and ESI-MS (SI, Figure S16b),
we found that a RuII species was formed as the decayed
product of 1 in this reaction.
As shown in Figure 10, DFT calculations (SI, Tables S5,
3
S10, and S15) show a single-step reaction with TST at 18.7
1
kcal mol-1 (at –40 qC). Interestingly, TST was lower in
energy at 14.6 kcal mol-1, a contributing factor to this
being the lower energy of the S = 0 RuII product. Given
the very low experimentally determined energy barrier
(13.0 kcal mol-1), we propose that two-spin state reactivity
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bonds are oxidized to give epoxide products via an OAT
and the accuracy of the peak positions of the Raman
mechanism. In sulfoxidation reaction, it is shown that 1
possesses an electrophilic character and conducts the
sulfoxidation via an OAT mechanism. DFT calculations
propose that two-spin state reactivity is in play in both
the epoxidation and sulfoxidation reactions. Taken
together, the present work adds one more piece of
evidence that the C-H bond activation of alkanes by a
mononuclear nonheme RuIVO complex occurs via an
oxygen non-rebound mechanism, as we have shown in
the reactions of mononuclear nonheme FeIVO, MnIVO,
CrIVO, and FeVO complexes.54-58 We have also shown that
the C-H bond activation is a preferred pathway over the
C=C double bond epoxidation in the oxidation of
cyclohexene by a mononuclear nonheme RuIVO complex,
similar to the case of mononuclear nonheme FeIVO
complex.59
bands was ± 1 cm-1. Product analysis was performed with
an Agilent Technologies 6890N gas chromatograph (GC)
and Thermo Finnigan (Austin, Texas, USA) FOCUS DSQ
(dual stage quadrupole) mass spectrometer interfaced
with Finnigan FOCUS gas chromatograph (GC-MS). 1H
NMR spectra were measured with Bruker model digital
AVANCE III 400 FT-NMR spectrometer.
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Generation and Characterization of 1. The yellowish
orange species 1 was generated by adding 1.2 equiv of
PhIO (dissolved in MeOH) to the freshly prepared CH3CN
solution of [RuII(terpy)(bpm)(H2O)](ClO4)2 (0.25 mM) at
25°C. The 18O-labeled RuIVO complex (1-18O) was prepared
by using PhI18O in CH3CN at 25 °C. PhI18O was prepared
by mixing PhI16O (1.0 mM) solution with H218O (10 μL)
and stirring for about 5 min. For the resonance Raman
experiment, 1-16O and 1-18O were generated by adding 1.2
equiv of PhI16O and PhI18O, respectively, to the solution of
[RuII(terpy)(bpm)(H2O)](ClO4)2 (4.0 mM) at 0 oC.
EXPERIMENTAL SECTION
Spin-State Measurement by 1H NMR Spectroscopy.
Materials. [RuII(terpy)(bpm)(H2O)](ClO4)2 and PhIO
were prepared according to the literature procedure.60,65-67
All other chemicals were obtained from Aldrich Chemical
Co. and used without further purification unless
otherwise indicated. Solvents were dried according to the
reported procedures and distilled under Ar prior to use.68
H218O (95 % 18O-enriched) was purchased from ICON
Services Inc. (Summit, NJ, USA).
1
The spin state of 1 was determined using the modified H
o
NMR method of Evans at –20 C.61,62 A WILMAD® coaxial
insert (sealed capillary) tube containing only the blank
acetonitrile-d3 solvent (with 1.0% TMS) was inserted into
the normal NMR tube containing the complex 1 (2.0 mM)
dissolved in acetonitrile-d3 (with 0.1% TMS). The chemical
shift of the TMS peak in the presence of the paramagnetic
metal complex was compared to that of the TMS peak in
the inner NMR tube. The magnetic moment was
calculated using the equation, μ = 0.0618(ΔνT/2fM)1/2,
where f is the oscillator frequency (MHz) of the
Instrumentation. UV-vis spectra were recorded on a
Hewlett
Packard
Agilent
8453
UV-visible
spectrophotometer equipped with a circulating water
bath or an UNISOKU cryostat system (USP-203, Japan).
Electrospray ionization mass spectra (ESI-MS) were
collected on a Thermo Finnigan (San Jose, CA, USA)
LCQTM Advantage MAX quadrupole ion trap instrument,
by infusing samples directly into the source at 20 μL/min
using a syringe pump. The spray voltage was set at 4.7 kV
and the capillary temperature at 80 oC. Electron
paramagnetic resonance (EPR) spectra were recorded at 5
K using X-band Bruker EMX-plus spectrometer equipped
superconducting spectrometer,
T
is the absolute
temperature, M is the molar concentration of the metal
ion, and v is the difference in frequency (Hz) between the
two reference signals.62 The 1H NMR Evans method
allowed us to determine magnetic moment of 3.3 μB for 1
o
in CH3CN at –20 C, indicating that 1 possesses an S = 1
spin state in CH3CN solution.
Kinetic Measurements. All reactions were run in a 1-cm
UV quartz cuvette and followed by monitoring UV-Vis
spectral changes of reaction solutions. Rate constants
were determined under pseudo-first-order conditions
(e.g., [substrate]/[1] > 10) by fitting the changes in
absorbance for formation of peaks at 460 nm in the C-H
activation, 450 nm in styrene reaction, and 485 nm in
thioanisoles oxidation. The substrates with varying BDE
values,69 such as, triphenylmethane (81.0 kcal mol-1),
cumene (84.5 kcal mol-1), ethylbenzene (87.0 kcal mol-1),
toluene (90.0 kcal mol-1), and cyclooctane (95.5 kcal mol-1)
were used in the C-H bond activation reactions by 1 in
CH3CN at 25 °C. The kinetic isotope effect value (KIE) for
the reaction of 1 and ethylbenzene was determined by
comparing k2 values obtained in the C-H and C-D bond
activation reactions of ethylbenzene-h10 and ethylbenzen-
d10, respectively. Similarly, the KIE values for the
oxidation reactions of styrene and cyclohexene by 1 were
obtained by using the k2 values of styrene-h8/styrene-d8
with
a dual mode cavity (ER 4116DM). The low
temperatures were achieved and controlled with Oxford
Instruments ESR900 liquid He quartz cryostat with
Oxford Instruments ITC503 temperature and gas flow
controller. The experimental parameters for EPR
measurements were as follows: microwave frequency =
9.646 GHz, microwave power = 1.0 mW, modulation
amplitude = 10 G, gain = 1 × 104, modulation frequency =
100 kHz, time constant = 40.96 ms and conversion time =
85.00 ms. Resonance Raman spectra were recorded using
liquid nitrogen cooled CCD detector (model LN/CCD-
1340 × 400PB, Princeton Instruments) attached to a 1-m
single polychromator (model MC-100DG, Ritsu Oyo
Kogaku). An excitation wavelength of 406.7-nm was
provided by a Kr+ laser (Spectra Physics, BeamLok 2060-
RM), with 4.0 mW power at the samples. All
measurements were carried out with a spinning cell (1000
rpm) at –20 oC. Raman shifts were calibrated with indene,
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and cyclohexene-h10/cyclohexene-d10, respectively. The
Gaussian.85 However, only the geometry and the
reactions of 1 and thioanisoles were studied at –40 oC. The
kinetic experiments were run at least in triplicate, and the
data reported represent the average of these reactions. k2′
values were obtained by dividing second-order rate
constants (k2) with the number of equivalent target C-H
bonds of substrates.
electronic energy (ΔE) were evaluated at the MECP, as
thermal contributions cannot be evaluated at non-
stationary points with regards to one specific spin state.
As the Def2-TZVPP energies were different for the
different spin states at the LACVP optimized structures of
MECP, the average was taken as the MECP Def2-TZVPP
value.
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Product Analysis. Products formed in the reactions of 1
with ethylbenzene, styrene, cyclohexene, and thioanisole
were analyzed by GC and GC-MS, and the product yields
were determined by comparing the peak areas of sample
products against standard curves prepared with known
authentic samples using internal standard decane. The
oxidation of ethylbenzene was achieved by mixing 0.10 M
ethylbenzene with 1.0 mM of 1. The 16O and 18O
ASSOCIATED CONTENT
Supporting Information. Figures S1-S16, Tables S1-S15 and
DFT calculated structure coordinates. This material is
available free of charge via the Internet at
http://pubs.acs.org.
AUTHOR INFORMATION
compositions
in
the oxygenated
products
of
ethylbenzene, styrene, cyclohexene, and thioanisole were
analyzed by comparing the relative abundances of m/z
values which shifted by two-mass units on incorporation
of 18O from 1-18O with that of 16O-products. The Ru
products (RuII and RuIII species) in the reaction solutions
of 1 with substrates were analysed using EPR and ESI-MS
spectroscopies.
Corresponding Author
* E-mail: wwnam@ewha.ac.kr
Author Contributions
§ These authors contributed equally to this work.
ACKNOWLEDGMENT
DFT Calculations. Density functional theory70 (DFT)
geometry optimizations and frequency calculations were
done at UB3LYP/LACVP level71-76 of theory (except for the
S atom, which used 6-311G*) using Gaussian 09 package.77
The free energies were evaluated at 25 °C, except for the
thioanisole sulfoxidation calculations that were evaluated
at –40 °C, in line with experiments. Solvent effects
(acetonitrile) were included in the geometry
optimizations by use of the CPCM implementation78 in
Gaussian 09. Single point energy evaluations were done at
the UB3LYP/Def2-TZVPP level79 including the solvent.
For singlet energies, as spin contamination was found to
be severe in some cases, corrections were carried out by
means of spin projection.80 Dispersion effects were
included by evaluating its effects at the converged
geometries by use of the DFT-D3 program using the
Becke-Johnson damping.81 The energy reference point in
each of the calculation series were the separated reactants
(except for the sulfoxidation reaction), as this enabled us
to obtain reasonable entropies (including dissociation
entropy) in combination with reasonable dispersion
values. These values were further corrected by a factor of
1.89 kcal mol-1, as modeling complexation in solvent
requires a correct treatment of the standard state.82 For
the sulfoxidation reaction, the energy reference point was
The authors acknowledge the NRF of Korea through CRI
(NRF-2012R1A3A2048842 to W.N.), MSIP (2013R1A1A2062737
to K.-B.C.) and GRL (NRF-2010-00353 to W.N.). S.S.
acknowledges the Israel Science Foundation (ISF grant
1183/12). SND thanks Goa University, Goa, India for grant of
leave.
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