Mild sp2Carbon-Oxygen Bond Activation by an Isolable Ruthenium(II) Bis(dinitrogen) Complex: Experiment and Theory

Article abstract of DOI:10.1021/acs.organomet.7b00632

The isolable ruthenium(II) bis(dinitrogen) complex [Ru(H)₂(N₂)₂(PCy₃)₂] (1) reacts with aryl ethers (Ar-OR, R = Me and Ar) containing a ketone directing group to effect sp²C-O bond activation at temperatures below 40 °C. DFT studies support a low-energy Ru(II)/Ru(IV) pathway for C-O bond activation: oxidative addition of the C-O bond to Ru(II) occurs in an asynchronous manner with Ru-C bond formation preceding C-O bond breaking. Alternative pathways based on a Ru(0)/Ru(II) couple are competitive but less accessible due to the high energy of the Ru(0) precursors. Both experimentally and by DFT calculations, sp²C-H bond activation is shown to be more facile than sp²C-O bond activation. The kinetic preference for C-H bond activation over C-O activation is attributed to unfavorable approach of the C-O bond toward the metal in the selectivity determining step of the reaction pathway.

Full text of DOI:10.1021/acs.organomet.7b00632

Article
pubs.acs.org/Organometallics
Mild sp2Carbon−Oxygen Bond Activation by an Isolable
Ruthenium(II) Bis(dinitrogen) Complex: Experiment and Theory
Samantha Lau,† Bryan Ward,† Xueer Zhou,† Andrew J. P. White,† Ian J. Casely,‡ Stuart A. Macgregor,§
and Mark R. Crimmin*,†
†Department of Chemistry, Imperial College London, South Kensington, London SW7 2AZ, United Kingdom
‡Johnson Matthey Technology Centre, Blounts Court, Sonning Common, Reading RG4 9NH, United Kingdom
§Institute of Chemical Sciences, Heriot-Watt University, Edinburgh, EH14 4AS, United Kingdom
S
* Supporting Information
ABSTRACT: The isolable ruthenium(II) bis(dinitrogen) com-
plex [Ru(H)2(N2)2(PCy3)2] (1) reacts with aryl ethers (Ar−OR,
R = Me and Ar) containing a ketone directing group to effect
sp2C−O bond activation at temperatures below 40 °C. DFT
studies support a low-energy Ru(II)/Ru(IV) pathway for C−O
bond activation: oxidative addition of the C−O bond to Ru(II)
occurs in an asynchronous manner with Ru−C bond formation
preceding C−O bond breaking. Alternative pathways based on a
Ru(0)/Ru(II) couple are competitive but less accessible due to the
high energy of the Ru(0) precursors. Both experimentally and by
DFT calculations, sp2C−H bond activation is shown to be more
facile than sp2C−O bond activation. The kinetic preference for C−H bond activation over C−O activation is attributed to
unfavorable approach of the C−O bond toward the metal in the selectivity determining step of the reaction pathway.
INTRODUCTION
■
The high content of elemental oxygen in the biopolymers that
constitute lignocellulosic biomass has inspired chemists to
develop new methods to break strong carbon−oxygen bonds.1,2
In organometallic chemistry, a series of nickel and ruthenium
precatalysts have been applied to reactions that transform
carbon−oxygen bonds of ethers into carbon−hydrogen,3,4
carbon−carbon,5−10 or carbon−boron11,12 bonds by hydro-
genolysis, cross-coupling, or borylation, respectively.13 Arguably
as important as the synthetic advances is understanding the
mechanism of C−O bond activation.
For most established catalyst systems based on nickel
complexes, at least two distinct pathways for C−O bond
cleavage have been proposed. While many studies invoke
Figure 1. sp2C−O bond activation by ruthenium phosphine
Ni(0)/Ni(II) catalytic cycles, oxidative addition of an sp2C−O
complexes.
bond of an ether to a nickel organometallic under catalytic
conditions has little experimental support.14−16 Martin and co-
workers have provided experimental and theoretical backing for
sp2C−O bond cleavage from a ligand-based reaction of a Ni(I)
arene complex.17
Ruthenium hydride catalysts have been reported in elegant
examples of cross-coupling reactions of aryl ethers with
organoboranes.18−22 These reactions rely on a suitable group
to direct the catalyst to an adjacent bond. In many cases C−H
and C−O bond functionalization are competitive. Kakiuchi and
co-workers have shown that the biaryl ether represented in
Figure 1 reacts with [Ru(H)2(CO)(PPh3)3] at high temper-
ature to give an isolable ruthenium-aryloxide product.23 This
reaction has been calculated to occur by oxidative addition of
the C−O bond to a 16-electron ruthenium(0) complex,
[Ru(PPh3)2(CO)(L)] (L = substrate coordinated through the
directing group).24 In related studies, Bergman and co-workers
have reported ruthenium catalysts for the hydrogen-shuttling
sp3C−O bond cleavage of 2-aryloxy-1-arylethanols, simple
models of the β-[O]-4′ linkage of lignin. Computational data
again support the involvement of a Ru(0)/Ru(II) redox couple,
Received: August 21, 2017
© XXXX American Chemical Society
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Figure 2. Crystal structures of 1, products of C−X activation 4a−c (X = H and O), and side products 6b and 7a.
and the key C−O bond breaking step is proposed to occur by
oxidative addition to Ru(0).25−27
1:1 ratio under an atmosphere of argon. Despite the discovery
of [Ru(NH3)5(N2)]2+ initiating the field of transition metal
dinitrogen chemistry,32,33 complex 1 is the first structurally
characterized bis(dinitrogen) complex of ruthenium (Figure 2,
Table 1).34,35 The single crystal data support the previous
assignment of 1 as a dihydride complex with cis-disposed
dinitrogen ligands.28,36
Here we show that [Ru(H)2(N2)2(PCy3)2] (1), originally
reported as a reactive intermediate prone to decomposition,28
can be isolated and effects both sp2C−H and sp2C−O bond
activation of methyl aryl and biaryl ethers under exceptionally
mild conditions (25−40 °C) provided the substrate contains a
suitable ketone directing group adjacent to the C−X bond (X =
H and OR). We rationalize the experimental findings through
an in-depth DFT analysis of the plausible pathways for C−X
bond activation. We conclude that consideration of both the
C−X bond breaking step and the energetics to form the
reactive transition metal fragment that participates in this step is
essential to compare the mechanisms of bond activation. We
show that the lowest energy pathway for 1 to effect bond
cleavage involves oxidative addition of the C−O bond to
Ru(II).
Table 1. Bond Lengths (Å) and Angles (deg) in 1 and 4a−c
1
4a
4b
4c
2.010(3)
2.013(3)
2.3382(7)
2.3392(6)
1.134(4)
1.116(3)
Ru−N
Ru−P
N−N
1.978(2)
1.9803(19)
1.975(2)
2.3529(7)
2.3542(7)
2.3562(6)
2.3571(6)
2.3459(5)
2.3460(5)
1.107(3)
1.105(2)
1.107(3)
Ru−C
O−Ru−C
2.034(2)
76.89(7)
2.042(2)
77.35(7)
2.043(3)
76.49(9)
EXPERIMENTAL SECTION
■
Full experimental details including the preparation of materials,
conditions of C−X bond activation reactions, spectroscopic and
crystallographic data, and details of the computational methods are
given in the Supporting Information.
Competitive C−H and C−O Bond Activation. The
reaction of 1 with 2-methoxyacetophenone (2a) or 2-p-
tolyloxyacetophenone (2b) in a 1:2 ratio proceeded rapidly
to form the corresponding cyclometalated species, 4a−b,
formed from C−H activation of 1 equiv of substrate. This
reaction is accompanied by transfer hydrogenation of the
second equivalent of substrate.37 Using a 1:1 ratio of reagents,
the same result is observed but with half of 1 unconsumed.
Addition of 1 to 2,6-dimethoxyacetophenone (3a) resulted in
facile C−O bond activation, again producing 4a as the
predominant ruthenium-containing product. Similar results
were obtained using biaryl ether 3b to form complex 4b.
Hence, 1 is capable of cleaving both sp2C−OMe and sp2C−
OAr bonds below 40 °C, and both reactions proceed slowly at
room temperature (Scheme 1). The Ru-containing side
RESULTS AND DISCUSSION
■
Isolation of [Ru(H)2(N2)2(PCy3)2] (1). Prepared from
[Ru(H)2(η2-H2)2(PCy3)2],29−31 1 is indefinitely stable under
an atmosphere of dinitrogen but subject to fast decomposition
when stored under argon or placed under vacuum. During
ligand exchange experiments to form 1, [Ru(H)2(η2-H2)(N2)-
(PCy3)2] was identified as an intermediate demonstrating
resonances at δ −8.48 ppm and δ 68.8 ppm by 1H and 31P{1H}
NMR spectroscopy, respectively. This complex has a diffusion
coefficient near-identical to that of 1 by DOSY studies. The
assignment of [Ru(H)2(η2-H2)(N2)(PCy3)2] was confirmed by
mixing the bis(dinitrogen) and bis(dihydrogen) complexes in a
B
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products of C−O bond cleavage are represented in Scheme 1,
and their formation is detailed below.
were observed in the expected region of the 13C NMR
spectrum and correlated with the Ru−H resonance by HMBC
experiments (4a, δ 212.2 ppm; 4b, δ 211.8 ppm).
Scheme 1. sp2C−O and sp2C−H Bond Activation of Methyl
Aryl and Biaryl Ethers with 1 and Key Side Products Formed
from C−O Activation
In the case of substrates 2a−b, despite the presence of both
ortho C−H and C−O bonds, exclusive C−H activation was
observed. Similarly, an intermolecular competition experiment
in which 1 was reacted with 2 equiv of 3a and 2 equiv of 2,2-
dimethylpropiophenone led to exclusive formation of C−H
activation product 4c (Scheme 2). Attempts failed to extend the
scope of the C−O cleavage reaction to substrates that did not
contain a suitable directing group such as anisole or benzyl
phenyl ether.
Scheme 2. Intermolecular Competition Experiment between
sp2C−O and sp2C−H Bond Activation
It is notable that although both C−O cleavage reactions
proceed to give organometallics in approximately 50% yield
neither contain the −OR fragment from the broken C−OR
bond. Furthermore, transfer hydrogenation of the organic
substrates occurs in both C−H and C−O activation reactions.
These data raise a number of questions: What is the destination
of the −OMe and −OAr groups following C−O bond
cleavage? What is the source of dihydrogen for the transfer
hydrogenation? Is transfer hydrogenation required to generate
a reactive Ru-complex capable of effecting C−O bond cleavage?
Ru-Containing Side Products from C−O Activation.
We hypothesized that the initial side products of C−O bond
activation are the alcohols, methanol (from 3a), and 4-methyl
phenol (from 3b) that go on to react with 1 at a faster rate than
the ethers themselves. In line with literature findings, methanol
reacts rapidly with 1 to form an equilibrium mixture of 5-N2/5-
H2 (Scheme 3a).28,42 These ruthenium carbonyl complexes are
formed during reactions of the methyl ether 3a with 1 in ∼30%
The propensity of [Ru(H)2(η2-H2)2(PCy3)2] to effect the
cyclometalation38 and catalytic functionalization39−41 of the
sp2C−H bond of aromatic substrates containing a suitable
directing group is well-established, but there is no precedent for
C−O bond activation with this complex. Control reactions
show that C−O bond activation is sensitive to the nature of the
ligands on ruthenium (N2 versus H2) and the atmosphere
under which the reaction is conducted. Reaction of 1 with 3a
under argon proceeded to give 4a over 5 h, while that under N2
required 24 h to reach completion, more accurately, t1/2(N2) =
6.0 h and t1/2(Ar) = 1.6 h. Reaction of 3a with [Ru(H)2(η2-
H2)2(PCy3)2] under an atmosphere of H2 fails to result in C−O
cleavage with transfer hydrogenation of the ketone observed
regardless of the reaction stoichiometry. In combination, the
experiments show that a labile N2 ligand on ruthenium is
necessary for C−O activation; indeed, exogenous N2 inhibits
the rate of this reaction.
1
yield as evidenced by 31P{1H} and H NMR spectroscopy.
Additional evidence for the formation of a metal carbonyl
under C−O cleavage conditions was provided by the reaction
of 1 with double 13C-labeled 2,6-dimethoxyacetophenone.
Following the reaction by 13C NMR spectroscopy revealed
the formation of a new metal carbonyl characterized by a
diagnostic resonance at δ 204.5 ppm (Scheme 3b). In
combination, these experiments provide compelling evidence
for the formation of a Ru−methoxide intermediate that readily
decomposes to a metal carbonyl. For comparison, nickel
alkoxide intermediates are prone to β-hydride elimination,43,44
and the formation of nickel carbonyl complexes has been
reported during reactions that break strong C−O bonds of
methyl aryl ethers.17,43
Monitoring the reaction of 1 with 4-methyl (or 4-tert-butyl)
phenol as a function of time revealed the formation of a mixture
of 6−8 prior to workup (Scheme 4).45 The structural
assignment was confirmed by a combination of 31P{1H} and
1H NMR spectroscopy (including VT and 2D experiments)
and X-ray crystallography. These experiments included the
isolation and separation of 6b, an analogue of 6a which proved
amenable to purification by fractional crystallization.
Complexes 4a and 4b were characterized by distinctive
1
triplets in the hydride region of the H NMR spectrum at δ
2
2
−14.89 (t, JP−H = 24.5 Hz) and −14.82 (t, JP−H = 24.1 Hz)
ppm, respectively, along with near-identical 31P{1H} resonances
(4a, δ 39.1 ppm; 4b, δ 39.9 ppm). While ultimately resolved by
X-ray diffraction studies (Figure 2), the retention of the
dinitrogen ligand on ruthenium was supported by infrared
absorptions for both Ru−H (4a, 1964 cm−1; 4b, 1983 cm−1)
and NN bonds (4a, 2078 cm−1; 4b, 2106 cm−1). The
ruthenium-bound carbon atoms of the cyclometalated ligands
C
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Scheme 3
a
b
Side products from C−O bond activation of 3a. Side products from reaction of 13C-3a with 1.
Scheme 4. Side Products from C−O Bond Activation of 3b
Square-based pyramidal ruthenium-aryloxide complex 6a is
the major side product observed in the C−O cleavage reaction
of 3b (∼20% yield). This complex is characterized by a
diagnostic resonance at δ 41.9 ppm in the 31P{1H} NMR
spectrum and a heavily shielded hydride resonance at δ −25.86
to generate coordinatively unsaturated Ru(0) complexes. These
latter species have been suggested by DFT to play an important
role in C−O and C−H bond activation and will be considered
as potential intermediates in the key bond breaking events in
the computational studies below (see “Plausible Pathways for
C−O Activation”).
1
(t, J = 19.2 Hz) ppm in the H NMR data. Complexes 7a and
8a are also both observed during C−O bond activation of 3b
with 1, albeit in smaller amounts than 6a, and are minor side
products of this reaction (∼5% combined yield).
While analogous reactions between Ru(II) hydrides and
phenols have been reported previously, there is a dearth of
single crystal X-ray studies to support the proposed structures
of the reaction products.46
An alternative explanation for the observed transfer hydro-
genation process is that 1 (or related species) could catalyze the
hydrogenation of the substrate. The H2 required is potentially
liberated during the C−X bond activation reactions. In the case
of C−H activation, H2 is formed from the breaking C−H and
Ru−H bonds, while in the case of C−OR activation, H2 is
generated by either dehydrogenation of the methoxide ligand to
form the carbonyl complex 5-N2/5-H2 (R = Me) or during
generation of the aryloxide 6a (R = Ar).
Summary of Experimental Findings. In combination, the
experimental data show the following: (i) Facile C−O
activation of aryl and methyl ethers occurs with the
ruthenium(II) complex 1 below 40 °C provided the substrate
contains a suitable directing group. (ii) The initial side products
of C−O bond activation are ruthenium−alkoxide/aryloxide
complexes. (iii) C−O bond activation can be inhibited by
addition of exogenous dinitrogen. (iv) C−H activation occurs
at a faster rate than C−O bond activation. The computational
studies presented below will rationalize these experimental data.
Computational Studies. Potential reaction mechanisms
were studied by DFT using the Gaussian 09 suite and
optimizations employed the BP86 functional.53−55 Ru and P
centers were described with Stuttgart RECPs and associated
basis sets (ECP28MWB for Ru and ECP10MWB for P).56−58
The P basis set was augmented with the addition of d-orbital
polarization (ζ = 0.387).59 6-31+G* basis sets were used for N
and O, and 6-31G** basis sets were used for all other
atoms.60−62 Free energies are corrected for both benzene
solvent (PCM approach) and dispersion effects (Grimme’s D3
parameter set with Becke−Johnson (BJ) damping).63,64 Full
Complex 6b contains, to the best of our knowledge, the first
structurally characterized trans-relation (O−Ru−N =
166.22(10)°) between a σ-aryloxide and dinitrogen ligand
(Figure 2). Both the Ru−O bond length (2.0181(18) Å) and
the Ru−N bond length (1.878(2) Å) are short. For
comparison, the former distance can be compared to the
range found in σ-phenoxide complexes (2.108(6)−2.152(2) Å)
and the latter to 4a−c (1.975(2)−1.9803(19) Å).45−48 These
data are a reflection of the weaker trans-influence of the σ-
aryloxide in comparison to the σ-aryl ligand47 and the π-basicity
of the aryloxide increasing back-donation to the dinitrogen
ligand. For comparison, trans-disposed ether and dinitrogen
ligands in a monomeric ruthenium complex have M−O and
M−N bond lengths of 2.117(3) and 1.946(3) Å, respec-
tively.49−51
Transfer Hydrogenation of the Ketone. Monitoring the
C−X bond activation reactions as a function of time revealed
that transfer hydrogenation of the ketone does not precede
bond activation but rather occurs at the same time. Esteruelas
and co-workers have also observed substrate hydrogenation
during C−H bond activation of ketones promoted by
ruthenium POP−pincer complexes.52 Transfer hydrogenation
of the first equiv of substrate with 1 could be a potential route
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details of the computational methods are provided in the
Supporting Information.
electron fragments from the Ru(II) precursors employed in
experiments?
Plausible Pathways for C−O Activation. In analyzing
plausible mechanisms of C−O bond activation from 1 we need
to consider both the key bond breaking step and the energetics
to form the reactive transition metal fragment that participates
in this step. Let us consider a series of plausible processes for
C−O bond cleavage, namely, (i) oxidative addition of the C−O
bond to Ru(0), (ii) hydrodeoxygenation by hydride attack on
the C−O bond of the Ru(II) coordinated substrate, and (iii)
oxidative addition of the C−O bond to Ru(II) (Scheme 5).
The results of the calculations that address this question for 1
are summarized graphically alongside the highest energy
transition states for the C−O activation step in Figure 3. The
data are presented in detail in Figures S27−31. Although
oxidative addition of a C−O bond to Ru(0) is facile, formation
of the required 16-electron intermediate is kinetically
challenging. This species could be generated by either reductive
elimination of H2 from 1 or transfer hydrogenation of a further
equivalent of the ketone substrate (as observed experimentally).
The highest transition states for these processes reach 32−38
kcal mol−1. In contrast, ligand exchange reactions that give rise
to intermediates capable of C−O bond activation at Ru(II) are
lower in energy, <30 kcal mol−1. Two pathways for C−O bond
activation are plausible from these Ru(II) intermediates
(hydrodeoxygenation or oxidative addition), and both have
transitions states that are similar to or lower than those
required to form the 16-electron Ru(0) species from 1. The
transition state for the SNAr path for C−O bond activation by
hydrodeoxygenation,67−69 is 1.8 kcal mol−1 higher than the
barrier involving oxidative addition of the C−O bond to Ru(II)
to form Ru(IV).
Scheme 5. Plausible Mechanisms for C−O Activation
To assess the possibility of a functional dependency effect on
competing pathways, we recomputed key intermediates and
transition states involved with a range of different functionals
(Table S2). The relative energy barriers were reproduced
consistently for each of the functionals and the Ru(II)/Ru(IV)
pathway was consistently found to be the most favorable
pathway of those examined. The results therefore indicate an
independence from functional influence.
The data suggest that while a number of pathways for C−O
bond activation are potentially competitive the oxidative
addition of the C−O bond to Ru(0) is the least accessible
due to the high barriers to form the required intermediate. In
the remainder of this manuscript, we provide a detailed analysis
of the lowest energy mechanism for C−O bond activation,
which involves changes in oxidative state between Ru(II) and
Ru(IV). We compare the pathways for C−O and C−H
cleavage that derive from common intermediates.
C−H Activation. Clot and co-workers have previously
calculated the C−H activation of acetophenone by [Ru-
(H)2(η2-H2)2(PMe3)2] and concluded that following displace-
ment of 2 equiv of H2 by the ketone and formation of an
agostic complex the reaction proceeds by a σ-complex assisted
Oxidative addition of C−O bonds of ethers to Ru(0)
carbonyl complexes has been widely invoked in Ru-catalyzed
cross-coupling reactions of ethers with boronic esters.18−22 Lin
and co-workers have recently calculated a low-energy transition
state for the oxidative addition of a C−O bond to the square-
planar 16-electron complex trans-[Ru(PPh3)2(CO)(L)].24
Directing-group-assisted C−H activation has been calculated
to occur by similarly facile Ru(0)/Ru(II) redox process.65,66
While the Ru(0)/Ru(II) mechanisms for C−X bond activation
are becoming generally accepted, the following question
remains: What are the barriers to generate the reactive 16-
Figure 3. Comparison of the highest energy transition states for TM fragment generation and C−O activation. Gibbs free energies in kcal mol−1. P =
PCy3.
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Figure 4. Structures of stationary points in C−H and C−O activation by 1.
Figure 5. Calculated pathways for C−H (red) and C−O (blue) activation. Gibbs free energies in kcal mol−1; liberated N2 not shown.
metathesis (σ-CAM)-like mechanism.70,71 Importantly, this
study demonstrated that the directing-group-assisted pathway
was considerably lower in energy than those which did not
involve coordination of the carbonyl group to ruthenium. In the
current case, while modification of the substrate to 2a and
ruthenium precursor to 1 produces a near-identical low-energy
reaction pathway for the C−H bond cleavage step, considering
the steps prior to coordination of the C−H bond has identified
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Figure 6. (a) NCI plot of Int-7 showing the key repulsive noncovalent interaction. (b) Molecular models of TS-2 and TS-5 with selected bond
lengths (Å). (c) Selected NBO second-order perturbation analysis data on Int-3 and Int-8. (d) NBO analysis showing the difference in the NPA
charges between Int-3/Int-2 and Int-7/Int-8.
further important features of this reaction (Figures 4 and 5).
Stepwise dissociation of 2 equiv of N2 from 1 with formation of
the five-coordinate intermediate Int-2 is endergonic, ΔG° =
+19.2 kcal mol−1, and provides the highest energy transition
state (TS-1) on the potential energy surface, ΔG⧧ = 26.1 kcal
mol−1 (Figure 3, blue curve).
TS-2 on the C−H activation pathway. This is therefore the
selectivity-determining step. Once Int-8 is formed, C−O
activation, like C−H activation, is facile and results in the
generation of Ru(IV) intermediate Int-9 at +19.8 kcal mol−1.
Formation of H2 from Int-9 via TS-7 generates the Ru(II)
complex, Int-10.
N2 dissociation from Int-1 can therefore be considered as the
rate-limiting step for C−H activation. Bond breaking and bond
making processes from Int-2 are facile. The highest transition
state in C−H bond breaking from Int-2 is TS-2, the approach
of the C−H bond to ruthenium to form the agostic complex
Int-3 with ΔG⧧ = 4.2 kcal mol−1. The C−H bond cleavage
transition state, TS-3, is only 0.2 kcal mol−1 higher in energy
than Int-3, and C−H bond cleavage is rapidly followed by H−
H bond formation along a flat potential energy surface on
which the ruthenium(II) complex Int-5 is the lowest energy
minimum.72 The reorganization of hydrogen atoms within the
equatorial plane of ruthenium(II) complexes is well-known to
proceed through low-energy, almost barrierless steps,38,73 and
related fluxional exchange process have been proposed to be
facilitated by nascent H···H−H bond formation in the ground
state due to donation from the σ-(M−H) orbital to the σ*-(H−
H) orbital.74,75 Dissociative exchange of H2 in Int-5 for N2
forms intermediate Int-6 and ultimately gives experimentally
isolated C−H activation product 4.
As with C−H activation, the bond breaking and making
processes that occur from Int-7 to Int-10 connect two Ru(II)
complexes by Ru(IV) stationary points. In contrast to the C−H
activation σ-CAM mechanism (in which the H from the C−H
bond effectively transfers directly on to the neighboring hydride
to form H2), as the C−OMe bond breaks, a new H−OMe bond
does not form directly. Instead, addition of the C−O bond to
Ru(II) occurs in concert with the reductive coupling of the two
hydride ligands already present, and this serves to re-establish
the Ru(II) oxidation state in Int-10. The nature of the C−X
bond breaking step in this pathway is subtly different to C−H
activation (vide infra). Methanol formation proceeds from Int-
10 through TS-8, breaking the H−H and Ru−OMe bonds
while simultaneously forming H−OMe and H−Ru bonds to
generate Int-11. Cundari, Gunnoe, and co-workers have
characterized related processes which involve the addition of
H2 (or C−H bonds) across Ru−OH and Ru−NH2 bonds.79,80
Methanol remains bound to the outer sphere of the ruthenium
complex in Int-11 through a dihydrogen bond (1.59 Å),
whereas the vacant site at Ru is stabilized through a C−H
agostic interaction from a tricyclohexylphosphine ligand
(Figure S34). Dissociation of methanol is facile, leaving the
five coordinate complex, Int-11, with cis-phosphine ligands
(Figures 4 and 5). Due to the ease of the ligand reorganization
processes, Int-11 can undergo an intramolecular isomerization.
Swinging of a phosphine from an equatorial to axial site yields
Int-12, which retains a C−H agostic interaction, and readily
coordinates dinitrogen forming the reaction products (Figure
S35). Several pathways were characterized for product
formation from Int-9 but that shown in Figures 4 and 5 was
the most accessible.81 Dehydrogenation of CH3OH to form 5-
N2/5-H2 by 1 was also investigated computationally. Formation
of the carbonyl complexes occurs through well-understood β-
hydride elimination and C−H activation steps all of which are
As previously concluded by Clot and co-workers, TS-3 could
be assigned as a stationary point with significant ruthenium(IV)
character.70 Moreover, in the current study Int-4 was identified
as the minimum that is directly connected to TS-3.76 QTAIM
and NBO calculations support the formulation of Int-4 as a
ruthenium(IV) trihydrido complex (Figure S32). A number of
Ru(IV) hydrido complexes are known,75,77 and Sabo-Etienne
and co-workers have recently characterized a Ru(IV)
hydridotrisilyl complex of the form [RuH(SiR3)3L3] by neutron
diffraction.78 Relaxed scan calculations along this potential
energy surface did not allow the identification of a concerted
C−H bond breaking and H−H bond forming process.
C−O Activation. Considering the analogous pathway for C−
O bond activation, the transition state for the approach of the
C−O bond toward ruthenium, TS-5, is higher in energy than
G
DOI: 10.1021/acs.organomet.7b00632
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Article
computed to be more accessible than the preceding C−O
activation (Figure S38).82,83
CONCLUSIONS
■
A comprehensive study of the organometallic products of the
sp2C−O bond activation of aryl methyl and biaryl ethers
bearing ketone directing groups by [Ru(H)2(N2)2(PCy3)2] has
been presented. Significant quantities of ruthenium-aryloxide or
ruthenium−carbonyl side products are formed during C−O
cleavage and their formation is rationalized based on the initial
formation of alcohol byproducts that react with [Ru-
(H)2(N2)2(PCy3)2] at a faster rate than the ethers. In substrates
where an ortho C−H bond is available there is a kinetic
preference for C−H over C−O bond activation.
DFT studies revealed that the lowest energy pathway for
bond activation involves the oxidative addition of the C−X
bond to Ru(II) to form Ru(IV) intermediates. In this pathway,
the approach of the C−X bond to Ru is selectivity determining.
Ligand dissociation, i.e., N2 dissociation, occurs en route to the
rate-determining step, and stationary points along the C−O
cleavage pathway require large changes in the P−Ru−P angle.
Alternative pathways for C−O bond activation were explored
and shown to be less favorable due to high-energy transition
states for either the bond activation step (SNAr/hydro-
deoxygenation) or the formation of the reactive intermediates
required for bond activation (oxidative addition to Ru(0)). The
discovery of a ruthenium(II) complex capable of C−O bond
activation under mild conditions (25−40 °C) and the new
Ru(II)/Ru(IV) mechanism we present for C−O bond cleavage
may have broad implications for the development of new
catalysts for chemical transformation of renewable resources.
Selectivity Determining Approach of the C−X Bond to
Ruthenium. Comparison of TS-2 and TS-5 explains the
experimentally observed selectivity. The free energy barrier for
C−H activation is considerably lower than C−O activation
(ΔΔG = 8.6 kcal mol−1). Approach of the C−O bond toward
ruthenium is less favored than that of the C−H bond due to a
combination of repulsive noncovalent interactions forcing
ligand reorganization. The importance of repulsive interactions
between substrates and transition metals has long been argued
when modeling reactions that break strong C−F bonds.84,85
NBO charge analysis highlights negative charge accumulation at
both Ru and O(Me) in TS-5. In contrast, the Ru(dπ)···C−
H(σ) repulsion is less significant. Consequently, as the C−O
bond approaches Ru, the acetophenone aryl ring is twisted out
of the equatorial plane in TS-5 as Ru interacts preferentially
with the ipso-carbon (vide infra). The structural reorganization
that is forced by distortion of the substrate is facilitated by the
flexibility of the coordinated phosphine ligands (Figure 6b).
The P−Ru−P angle in TS-5 of 132° is ∼30° smaller than that
in TS-2 (Table S3). The phosphine ligands are ultimately
forced into a cis-like geometry in Int-9. It is clear despite the
energetic penalty that accompanies the structural distortion that
the elasticity of the P−Ru−P angle is important for C−O bond
cleavage. A number of relevant ruthenium complexes with cis-
disposed PCy3 ligands are known.86−88
Breaking of the C−X Bond. Both bond activation steps
involve oxidative addition of the C−X bond to Ru(II). There
are, however, subtle differences between the C−H and C−O
cleavage mechanisms. As both pathways contain an early
transition state for C−X bond activation, comparison of Int-3
and Int-8 elucidates the key differences. Second-order
perturbation analysis allows Int-3 to be classified as a typical
agostic complex. Donation from the σ-(C−H) orbital to the
σ*-(Ru−H) is accompanied by back-donation from a filled d-
orbital of Ru to the σ*-(C−H) (Figure 6c). NBO calculations
show that formation of this agostic complex from Int-2 occurs
with only minor perturbation of the electron density at the Ru
and C centers (Figure 5d). It can be concluded that C−H bond
breaking occurs by population of the σ*-(C−H) orbital with
electrons from Ru and formation of a Ru(IV) organometallic.
In contrast, formation of Int-8 from Int-7 on the C−O
activation pathway occurs with pyramidalization at the ipso-
carbon of the aromatic ring and accumulation of charge at both
this site and, to a lesser extent, the ortho- and para-positions.
Concurrently the Ru center undergoes charge depletion
(Figure 6d). While QTAIM analysis shows bond critical
paths between Ru−C, C−O, and O−Ru in this intermediate,
second-order perturbation analysis from the NBO calculations
suggests that it cannot be simply described as a σ-complex
(Figure S40). No significant donation nor back-donation to or
from the σ-(C−O) bond is calculated (Figure 6). Moreover the
small positive ∇2ρb and negative Hb values at the bond critical
points between Ru and C from the QTAIM data indicate the
formation of a partially covalent bond. In combination the data
suggest an asynchronous pathway for C−O bond activation in
which Ru−C bond formation precedes Ru−O bond formation.
This bond breaking/bond making event is reminiscent of
nucleophilic aromatic substitution. Attack of the metal-based
nucleophile on the aromatic ring is followed by transfer of the
methoxy group to the forming Ru(IV) center.
ASSOCIATED CONTENT
■
S
* Supporting Information
Editable NMR data and coordinate files are available via a
repository maintained by Imperial College London (DOI:
10.14469/hpc/2100). The Supporting Information is available
free of charge on the ACS Publications website at DOI:
10.1021/acs.organomet.7b00632.
Experimental procedures, details of the DFT studies,
single crystal X-ray data, and multinuclear NMR spectra
(PDF)
Cartesian coordinates (XYZ)
Accession Codes
CCDC 1530724−1530730 contain the supplementary crystal-
lographic data for this paper. These data can be obtained free of
charge via www.ccdc.cam.ac.uk/data_request/cif, or by email-
ing data_request@ccdc.cam.ac.uk, or by contacting The
Cambridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: m.crimmin@imperial.ac.uk.
ORCID
Bryan Ward: 0000-0002-1744-4930
Stuart A. Macgregor: 0000-0003-3454-6776
Mark R. Crimmin: 0000-0002-9339-9182
Author Contributions
S.L. and B.W. contributed equally to the creation of this work.
Notes
The authors declare no competing financial interest.
H
DOI: 10.1021/acs.organomet.7b00632
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Article
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ACKNOWLEDGMENTS
■
We are grateful to the European Research Council for provision
of a starting grant (FluoroFix:677367) and the Royal Society
for a University Research Fellowship (UF090149). Johnson
Matthey is thanked for generous support. Stephen Bennett is
thanked for productive discussions. Prof. Michael Whittlesey
(University of Bath) is thanked for insightful comments and
sharing data prior to publication. The EPSRC are thanked for
support in the form of a CASE award.
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