Cooperative activating effects of metal ion and Br?nsted acid on a metal oxo species

Article abstract of DOI:10.1039/d0sc04069j

Metal oxo (MO) complexes are common oxidants in chemical and biological systems. The use of Lewis acids to activate metal oxo species has attracted great interest in recent years, especially after the discovery of the CaMn4O5 cluster in the oxygen-evolvin

Full text of DOI:10.1039/d0sc04069j

Chemical
Science
View Article Online
View Journal
EDGE ARTICLE
Cooperative activating effects of metal ion and
Brønsted acid on a metal oxo species†
Cite this: DOI: 10.1039/d0sc04069j
a
b
c
c
c
*
Li Ma, Po-Kam Lo, Chi-Keung Mak, Kai-Chung Lau
*
All publication charges for this article
have been paid for by the Royal Society
of Chemistry
Gui Chen,
and Tai-Chu Lau
c
*
Metal oxo (M]O) complexes are common oxidants in chemical and biological systems. The use of Lewis
acids to activate metal oxo species has attracted great interest in recent years, especially after the
discovery of the CaMn4O5 cluster in the oxygen-evolving centre of photosystem II. Strong Lewis acids
such as Sc3+ and BF3, as well as strong Brønsted acids such as H2SO4 and CF3SO3H, are commonly used
to activate metal oxo species. In this work, we demonstrate that relatively weak Lewis acids such as Ca2+
and other group 2 metal ions, as well as weak Brønsted acids such as CH3CO2H, can readily activate the
Received 27th July 2020
Accepted 20th October 2020
stable RuO4 complex towards the oxidation of alkanes. Notably, the use of Ca2+ and CH3CO2H
ꢀ
together produces a remarkable cooperative effect on RuO4ꢀ, resulting in a much more efficient
oxidant. DFT calculations show that Ca2+ and CH3CO2H can bind to two oxo ligands to form a chelate
ring. This results in substantial lowering of the barrier for hydrogen atom abstraction from cyclohexane.
DOI: 10.1039/d0sc04069j
rsc.li/chemical-science
to activate Fe(IV) and Mn(IV) oxo complexes,12,13 as well as metal
superoxo species.14,15
Introduction
There is also much interest in the use of the relatively weak
Lewis acid, Ca2+, to activate M]O because of its relevance to the
CaMn4O5 cluster in Photosystem II; although as expected, its
effect is usually much smaller than those of Sc3+ or BF3. For
example, Agapie et al. reported that Ca2+ and other metal ions
can increase the reduction potentials (E0) of manganese oxo
clusters, and there is a linear correlation between E0 and pKa of
the metal ions.16,17 Ca2+ can also enhance the catalytic water
oxidation activity of manganese oxides18,19 and induce the
oxidative release of O2 from a non-heme iron peroxo complex.20
We have also recently reported tꢀhat Ca2+ can increase the rate of
oxidation of alcohols by MnO4 (ref. 21) and induce intermo-
High-valent metal oxo (M]O) complexes are common oxidants
in the chemical laboratory and in biological systems. Brønsted
acids have long been used to increase the oxidizing power of
M]O via protonation of the oxo ligand (M]O + HX / MꢀOH+
+ Xꢀ). However, in recent years, the use of Lewis acids (LA) such
as metal ions and boranes to activate M]O has received
tremendous attention (M]O + LA / M]O–LA).1–3 In partic-
ular, the interest in understanding the interaction of Lewis
acids with metal oxos is stimulated by the discovery that the
oxygen-evolving center (OEC) of photosystem II (PSII) is
composed of a CaMn3O4 cubane and a dangling Mn linked via
two m-oxos.4–10 A possible role of Ca2+ is to function as a Lewis
acid to modulate the redox reactivity of the manganese oxo
complexes.
2ꢀ
lecular O–O coupling of FeO4 to give O2.22 So far, signicant
activating effects of Ca2+ are only reported on metal oxo
complexes that are thermodynamically strong oxidants. On the
other hand, there has been little or no report on the activation
of metal oxo species by weak Brønsted acids such as alkanoic
acids.
We have been investigating the effects of Lewis acids on the
reactivity of simple metal oxo species bearing two or more oxos
without bulky ancillary ligands.11,21–25 In this type of systems,
more than one oxo sites are available for binding to two or more
metal ions or Brønsted acids. We report herein the activation of
a stable metal oxo complex, RuO4ꢀ, by weak Lewis acids such as
Ca2+ and other group II ions, as well as by weak Brønsted acids
such as CH3CO2H. Although iron oxo complexes are common
oxidants in chemical and biological systems, they are usually
relatively unstable. Hence, we choose to investigate a very stable
ruthenium oxo species. Although in a high oxidation state of
Strong Lewis acids such as BF3 and Sc3+ are usually used to
activate metal oxo species. For example, we have reported that
the oxidation of alkanes by MnO4ꢀ is accelerated by over seven
orders of magnitude in the presence of BF3.11 The strong Lewis
acid Sc3+ and the strong Brønsted acid CF3SO3H have been used
aDongguan Cleaner Production Technology Center, School of Environment and Civil
Engineering, Dongguan University of Technology, Dongguan, Guangdong 523808,
China
bDepartment of Chemistry, Jinan University, Guangzhou, 510632, China
cDepartment of Chemistry, City University of Hong Kong, Tat Chee Avenue, Kowloon
Tong, Hong Kong, China. E-mail: bhtclau@cityu.edu.hk; kaichung@cityu.edu.hk;
chikmak6@cityu.edu.hk
† Electronic supplementary information (ESI) available. See DOI:
10.1039/d0sc04069j
This journal is © The Royal Society of Chemistry 2020
Chem. Sci.

View Article Online
Chemical Science
Edge Article
+VII, RuO4ꢀ is a mild oxidant that readily oxidizes alcohols but The UV/Vis spectrum of the solution also remained unchanged
is inactive towards alkanes. However, in the presence of a few aer 5 days. However, upon adding 4 equiv. of BF3 to [nPr4N]
equiv. of group 2 metal ions or acetic acid, it readily oxidizes [RuO4] in CH3CN, 10 mol% of cyclohexanone was produced
cyclohexane at ambient conditions. Notably, the use of Ca2+ and within 3 h at 23 ꢁC (Fig. 1b and Table S2†). Again, no cyclo-
CH3CO2H together produces a remarkable cooperative effect on hexanol product could be detected. More signicantly, Ca(OTf)2
RuO4ꢀ, resulting in a much more efficient oxidant than the use is also able to activate RuO4ꢀ, and a higher yield of 14 mol% of
of a strong Lewis acid in the presence or absence of a Brønsted cyclohexanone was attained (Fig. 1b, S1 and Table S2†). As will
acid.
be described below, the RuO4ꢀ/Ca2+ system functions as one-
electron oxidant, and since the oxidation of cyclohexane to
cyclohexanone is a four-electron process, the actual yield is
56%. Other group II metal ions were also found to activate
RuO4ꢀ, with cyclohexanone production ranging from 11 to
15 mol% (Fig. 2, Table S2†). The relatively strong Lewis acid
Sc(OTf)3 was also used and it gave the highest amount of
23 mol% of cyclohexanone. The rate and yield decrease in the
order of Sc3+ (pKa ¼ 4.3) > Mg2+ (11.2) > Ca2+ (12.7) > Sr2+ (13.2)
>> Ba2+ (13.4); this trend correlates with their pKa values in H2O,
which is a measure of their Lewisꢀacidity.28 These results indi-
cate that the oxo ligands in RuO4 are much more basic than
those in RuO4, so they readily bind to Lewis acids. Electron-
withdrawing by the Lewis aꢀcids via the oxo ligand enhances
Results and discussion
Effects of Leꢀwis acids on oxidation of cyclohexane by RuVIIIO4
and RuVIIO4
Tetraoxo complexes of ruthenium in oxidation states +VIII and
+VII are known, with RuVIIIO4 being a much stronger oxidant
than RuVIIO4ꢀ. As a comparison, we have initially chosen to
study the effects of Brønsted and Lewis acids (metal ions and
BF3) on the oxidation of alkanes by RuO4. RuO4 is a strong
oxidant that is known to oxidize alkanes slowly at room
temperature.26 In our hands, when RuO4 (0.01 M) was treated
with an excess of cyclohexane (1.0 M) in CH3CN, 0.2 mol of
cyclohexanone/mol of RuO4 (20 mol%) was produced aer 5 h at
23 ꢁC, as analysed by GC and GC/MS (Fig. 1a and Table S1†). No
cyclohexanol could be detected. Sinceꢀwe previously reported
the oxidizing power of RuO4
.
Kinetics of the oxidation of cyclohexane by RuO4ꢀ/Ca2+
that the oxidation of alkanes by MnO4 is greatly enhanced by The initial rate for cyclohexanone production by [nPr4N][RuO4]
just a few equiv. of BF3,11 we attempted to do the same with increases with [Ca2+] but eventually levels off at [Ca2+] > 5 mM
RuO4. However, when BF3 was added to RuO4, no enhancement (Fig. 3a). A plot of 1/(initial rate) versus 1/[Ca(OTf)2] is linear
ꢀ
in the rate of cyclohexane oxidation was observed; on the (Fig. 3b). In addition, when the concentration of RuO4 was
contrary, a lower yield of cyclohexanone (11 mol%) was ob- doubled, the initial rate was also doubled. Such a kinetic
tained (Fig. 1a and Table S1†). We then examined if Ca2+ can behavior can be represented by eqn (1) and (2). The reacting
activate RuO4, but virtually no effect on cyclohexane oxidation calcium species is proposed to be Ca(OTf)+, as supported by
ꢀ
was observed when a few equiv. of Ca(OTf)2 (OTf is CF3SO3
)
results of DFT calculations described below. The initial rate of
was added. We also tried to activate RuO4 with Brønsted acids the reaction is shown in eqn (3).
such as CF3SO3H and CH3CO2H (AcOH), but again there were
K Â
ꢀÃ
CaðOTfÞþ þ RuO4ꢀ # CaðOTfÞþ$RuO4
(1)
(2)
no effects. These results indicate that the oxo ligands in the
highly electrophilic RuO4 have little or no affinity for CH3CO2H
and various Lewis acids.
Â
ꢀÃ
k
CaðOTfÞþ$RuO4 þ c ꢀ C6H12 / products
ꢀ
On the other hand, RuO4 is a much weaker oxidant than
Â
Ã
RuO4; it is known to oxidize alcohols but not alkanes.27 When
we treated [nPr4N][RuO4] with cyclohexane in CH3CN, no
product could be detected aer 5 days at 23 ꢁC. Electrospray
ionization mass spectrometry (ESI/MS) of the solution aer 5
days shows that RuO4ꢀ and nPr4N+ are the only species present.
Â
ꢀÃ
kK CaðOTfÞ
2
Â
Ã
Initial rate ¼
RuO4 ½c ꢀ C6H12ꢂ
(3)
1 þ K CaðOTfÞ
2
Fig. 1 Time traces for cyclohexane oxidation by (a) RuO4/Lewis acid Fig. 2 Effects of various Lewis acids on cyclohexane oxidation by
and (b) RuO4ꢀ/Lewis acid in CH3CN. Conditions: RuO4 or [nPr4N] RuO4ꢀ in CH3CN. Conditions: [nPr4N][RuO4] (0.01 M), Lewis acid (0.04
[RuO4] (0.01 M), Lewis acid (0.04 M), cyclohexane (1.0 M) at 23 ꢁC.
M), cyclohexane (1.0 M) at 23 ꢁC.
Chem. Sci.
This journal is © The Royal Society of Chemistry 2020

View Article Online
Edge Article
Chemical Science
Fig. 4 (a) Effects of CH3CO2H on cyclohexane oxidation by RuO4ꢀ in
CH3CN. Conditions: [nPr4N][RuO4] (0.01 M), cyclohexane (1.0 M) in
CH3CN at 23 ꢁC. (b) Plot of initial rate versus [AcOH]. (slope ¼ (2.72 ꢃ
0.13) ꢄ10ꢀ6, y-intercept ¼ -(3.33 ꢃ 3.82) ꢄ 10ꢀ8, r ¼ 0.9908).
ꢀ
Fig. 3 Effects of [Ca(OTf)2] on cyclohexane oxidation by RuO4 in
CH3CN. Conditions: [nPr4N][RuO4] (0.01 M), cyclohexane (1.0 M) in
CH3CN at 23 ꢁC. (a) Plot of initial rate vs. [Ca(OTf)2]. (b) Plot of 1/initial
rate vs. 1/[Ca(OTf)2] (slope ¼ (3.16 ꢃ 0.15) ꢄ103, y-intercept ¼ (2.16 ꢃ
0.06) ꢄ 106, r ¼ 0.988).
Κ0
Â
Ã
Â
Ã
From Fig. 3b, k ¼ 1/(intercept [RuO4ꢀ]) ¼ (4.63 ꢃ 0.13) ꢄ 10ꢀ5
Mꢀ1 sꢀ1 and K ¼ intercept/slope ¼ (6.83 ꢃ 0.18) ꢄ 102 Mꢀ1 at
23 ꢁC. The observed equilibrium constant K indicates relatively
strong binding of Ca(OTf)+ to RuO4ꢀ, in accordance with the
observed rate saturation behaviour.
*
RuðOÞ ðOHÞ þ CH3CO2H ) CH3CO2H$RuðOÞ ðOHÞ (6)
3
3
k0
!
Â
Ã
CH3CO2H$RuðOÞ ðOHÞ þ c ꢀ C6H12 products
(7)
3
k0K0½CH3CO2Hꢂ
Â
ꢀÃ
Initial rate ¼
RuO4 ½c ꢀ C6H12ꢂ (8)
1 þ K0½CH3CO2Hꢂ
ꢀ
Activation of RuO4 by Brønsted acids
At K0[CH3CO2H] I 1
The effects of Brønsted acids on cyclohexane oxidation by
RuO4ꢀ were also investigated. Addition of 1 equiv. of the strong
acid CF3SO3H (pKa ¼ 0.23 in H2O) to [nPr4N][RuO4] (0.01 M) in
CH3CN containing excess cyclohexane led to the formation of
15 mol% of cyclohexanone aer 3 h at 23 ꢁC. However, addition
of $4 equiv. of CF3SO3H to [nPr4N][RuO4] resulted to rapid
formation of a black precipitate with only a trace amount of
cyclohexanone. Such a phenomenon is due to disproportion-
Initial rate ¼ k0K0[AcOH][RuO4ꢀ][c-C6H12] ¼ kAcOH[AcOH]
[RuO4ꢀ][c-C6H12]
(9)
From the slope of Fig. 4b and using [RuO4ꢀ] ¼ 0.01 M and [c-
C6H12] ¼ 1.0 M, kAcOH is found to be (2.72 ꢃ 0.13) ꢄ10ꢀ4 Mꢀ2
sꢀ1 at 23 C.
ꢁ
ꢀ
ation of RuO4 , as represented by eqn (4):29
Cooperative activating effects of metal ions and AcOH
ꢀ
4RuO4 + 4H+ / 3RuO4 + RuO2 + 2H2O E0 ¼ 0.46 V (4)
ꢀ
Remarkably, when the oxidation of cyclohexane by RuO4 was
carried out in the presence of Ca2+ and AcOH, both the rate and
product yield were enhanced, as shown in Fig. 5. The amount of
cyclohexanone produced by the RuO4ꢀ/Ca2+/AcOH system is
38 mol%, compared with ca. 16 mol% by both RuO4ꢀ/Ca2+ and
RuO4ꢀ/AcOH systems. In this case, the oxidation state of the
ruthenium product was found to be +5 (see below, Fig. S3†), so
this system functions as a two-electron oxidant and the actual
yield is 76%, higher than the 64% using Ca2+ or AcOH alone.
Interestingly, [nPr4N][RuO4] is also readily activated by the
relatively weak acid CH3CO2H (pKa ¼ 4.76) to oxidize cyclo-
hexane to cyclohexanone, with no evidence of disproportion-
ation even in the presence of high concentrations of AcOH (>1
M). Upon addition of 12–48 equiv. of AcOH to [nPr4N][RuO4] in
CH3CN containing excess cyclohexane, the brown solution
gradually turned green, and 16 mol% of cyclohexanone was
produced within 1–2 h at 23 ꢁC. The oxidation state of the
ruthenium product was determined to be +6 (see below,
Fig. S2†), hence the actual yield is 64%. Although the yield is
independent of [AcOH], the rate of oxidation increases with
increasing [AcOH] (Fig. 4); a plot of the initial rate versus [AcOH]
gives a straight line. The initial rate is also doubled when
[RuO4ꢀ] is doubled. A proposed reaction scheme is shown in
eqn (5)–ꢀ(7). The rst step involves protonation of an oxo ligand
of RuO4 by AcOH, this step is supported by DFT calculations
described below. The resulting [Ru(O)3(OH)] species is
hydrogen-bonded to a second AcOH molecule to generate the
active intermediate [AcOH$Ru(O)3(OH)] that oxidizes cyclo-
hexane. The rate law is shown in eqn (8); at K0[CH3CO2H] I 1,
the rate law becomes that of eqn (9).
Fig. 5 Time trace for cyclohexane oxidation by [nPr4N][RuO4] (0.01 M)
in CH3CN at 23 ꢁC in the presence of (a) 1 equiv. Ca2+, (b) 12 mol equiv.
(5) of AcOH and (c) 1 mol equiv. Ca2+ + 12 mol equiv. AcOH.
ꢀ
ꢀ
RuO4 + CH3CO2H / [Ru(O)3(OH)] + CH3CO2
This journal is © The Royal Society of Chemistry 2020
Chem. Sci.

View Article Online
Chemical Science
Edge Article
The yield of cyclohexanone was increased to 92% when the
amount of acetic acid was increased to 250 equiv. (CH3CN/
AcOH: 6/1, Table 1). Note that in the absence of Ca(OTf)2, the
yield of cyclohexanone did not increase with [AcOH], as illus-
trated in Fig. 4a. Similar cooperative effects of M2+ and AcOH
were also found for other group 2 ions (Table 1), with
a maximum yield of 99% observed for Sr2+/AcOH. However, no
such cooperative effects were found for stronger Lewis acids
such as BF3 and Sc(OTf)3, the yields remain the same in the
absence or presence of AcOH. These results demonstrate the
strong cooperative effects of relatively mild Brønsted and Lewis
acid in activating a metal oxo species. Although the reaction rate
is lower than that of BF3 or Sc(OTf)3, the Group 2 ion/AcOH
combination is much more efficient in terms of product yield.
Similar to the case of CF3SO3H discussed above, partial
Fig. 6 (a) Plot of initial rate vs. [Ca2+] for the Ca(OTf)2/AcOH activated
ꢀ
oxidation of cyclohexane (0.10 M) by RuO4 (0.01 M) in CH3CN at
23.0 ꢁC. (b) The corresponding plot of 1/initial rate vs. 1/[Ca2+]. Slope ¼
(6.29 ꢃ 0.64) ꢄ103, y-intercept ¼ (1.29 ꢃ 0.09) ꢄ 106, r ¼ 0.9504.
ꢀ
Conditions: RuO4 (0.01 M); cyclohexane (1.0 M); AcOH (0.12 M);
Ca(OTf)2 (0.002 M ꢀ 0.040 M).
ꢀ
decomposition of RuO4 occurs in the presence of a strong
Lewis acid, hence resulting in lower yields.
From eqn (11) and Fig. 6b, K00 and k00 are found to be (2.05 ꢃ
0.31) ꢄ 102 Mꢀ1 and (6.49 ꢃ 0.45) ꢄ 10ꢀ4 Mꢀ1 sꢀ1, respectively.
A similar cooperative effect was also found for Mg2+/AcOH
(Fig. S4†). However, no increase in rate and yield were found for
Sc3+/AcOH (Fig. S5†).
The kinetics of cyclohexane oxidation by RuO4ꢀ/Ca2+/AcOH
were investigated. Saturation kinetics were also observed when
[Ca2+] was increased (Fig. 6). Based on Fig. 6 and the mecha-
nisms proposed above for RuO4ꢀ/Ca2+ and RuO4ꢀ/AcOH, the
mechanism for this system can be represented by the following
equations.
Ruthenium intermediates and products
ꢀ
ꢀ
RuO4 + CH3CO2H / [Ru(O)3(OH)] + CH3CO2
(10)
Electrospray ionization mass spectrometry (ESI/MS) waꢀs
employed to detect any intermediate formed between RuO4
and Ca2+. The mass spectrum of [nPr4N][RuO4] in CH3CN
exhibits a single peak at m/z 166.1 due to RuO4ꢀ (Fig. S6†). Upon
addition of 0.25 equiv. of Ca(OTf)2, a new peak at m/z 653.9
appeared, which is assigned to [RuO4$Ca(CF3SO3)2$CF3SO3H]ꢀ
(Fig. S7†). MS/MS of this ion (m/z 653.9) gives fragment peaks
Â
Ã
RuðOÞ ðOHÞ þ CaðOTfÞþ
3
K00 Â
Ã
þ
*
þ CH3CO2H ) CaðOTfÞ $CH3CO2H$RuðOÞ ðOHÞ (11)
3
k00
Â
Ã
CaðOTfÞþ$CH3CO2H$RuðOÞ ðOHÞ þ c ꢀ C6H12 products
!
3
(12)
due to CF3SO3ꢀ (m/z 148.9) and RuO4ꢀ (m/z ¼ 165.9) (Fig. S8†).
This result provides evidence for the binding of Ca2+ to RuO4
.
ꢀ
The rate-law is as shown in eqn (13):
The brown color of the solution of [nPr4N][RuO4]/Ca(OTf)2
gradually lightened during cyclohexane oxidation, eventually
a dark brown precipitate was observed and the solution became
Â
Ã
k00K00 CaðOTfÞ
Â
ꢀÃ
2
Â
Ã
Initial rate ¼
RuO4 ½AcOHꢂ½c ꢀ C6H12ꢂ
1 þ K00 CaðOTfÞ
colorless. The dark precipitate, which is probably a Ca2+
-
2
(13)
bridged polymeric species, was dissolved in 0.1 M HNO3 and the
solution was titrated spectrophotometrically with the strong
oxidant (NH4)2Ce(NO3)6 (Ce(IV)). Upon addition of Ce(IV) to the
ruthenium product solution, the characteristic vibronic-
structured peaks at around 380 nm due to RuO4 appeared,26
and 2.3 ꢃ 0.3 equiv. of Ce(IV) was consumed (Fig. S2†). This
result indicates that the oxidation state of Ru in the dark brown
Table 1 Oxidation of cyclohexane by [nPr4N][RuO4]/Lewis acid in
CH3CN/AcOH (6:1, v/v)a
Entry a
Lewis acid
Yield of cyclohexanoned (%)
Time
ꢀ
product is +6 and hence the Ca2+/RuO4 system acts as one-
1
Ca(OTf)2
Ca(OTf)2
Ca(OTf)2
Sr(OTf)2
Mg(OTf)2
Ba(OTf)2
BF3
92
92
91
99
86
86
42
46
5 h
5 h
5 h
5 h
5 h
5 h
3 min
6 min
2b
3c
4
electron oxidant in the reaction with cyclohexane.
In cyclohexane oxidation by [nPr4N][RuO4]/AcOH, the brown
solution gradually turned dark green but no precipitate was
observed. ESI/MS of the dark green solution shows the
appearance of a peak at m/z 209 (Fig. S9†), which can be
assigned to [RuVIO3(AcO)]ꢀ. When CH3CO2H was replaced by
CD3CO2D, the m/z 209 peak was shied to m/z 212, indicating
that the m/z 209 peak consists of 1 AcOꢀ ion. The assignment of
+6 oxidation state to the ruthenium product is also supported by
Ce(IV) titration, which consumes two equiv. of Ce(IV) to generate
RuO4. Hence the RuO4ꢀ/AcOH system also functions a one-
electron oxidant.
5
6
7
8
Sc(OTf)3
Conditions: [nPr4N][RuO4], 0.01 M; Lewis acid, 0.04 M; cyclohexane,
a
b
c
1.0 M; solvent, CH3CN/HOAc (6:1, v/v); at 23 ꢁC. Under argon. In
the presence of 10 equiv. of BrCCl3, only trace amount of
a
d
bromocyclohexane was detected.
Yield of cyclohexanone was
calculated based on [nPr4N][RuO4] acting as two-electron oxidant.
Yield ¼ (mol of cyclohexanone)/(mol of [nPr4N][RuO4]) ꢄ 2 ꢄ 100%,
no cyclohexanol was detected.
Chem. Sci.
This journal is © The Royal Society of Chemistry 2020

View Article Online
Edge Article
Chemical Science
On the other hand, spectrophoꢀtometric titration of the the HAT is 26.8 kcal molꢀ1 in CH3CN. Such a large DG298‡ agrees
product solution of Ca2+/AcOH/RuO4 aer cyclohexane oxida- with the experimental observation that RuO4 hardly reacts
ꢀ
tion shows that it consumes 3.1 ꢃ 0.2 equiv. of Ce(IV), hence in with cyclohexane at room temperature. The C1 of the cyclohexyl
this case the oxidation state of the Ru product is +5 and the radical in INT2(RuO4ꢀ) bears ꢀ0.93 electrons, consistent with
system is a two-electron oxidant towards cyclohexane (Fig. S3†). a HAT process. The cyclohexyl radical then binds to another oxo
ligand to generate an alkoxo intermediate [RuO2(OH)
(OC6H11)]ꢀ via TS2(RuO4ꢀ). It should be noted that the step
Mechanistic studies
aer H-abstraction is not characterized as a rebound step, in
The same results were obtained for cyclohexane oxidation
contrast to cytochrome P450 and other mono-oxo species.
carried out under argon or air (Tables 1 and S2†). Also, the
Rather, another oxo group which is not used for H-atom
addition of BrCCl3, a radical scavenger, had little effects on the
abstraction combines with the carbon atom with a low
oxidation of cyclohexane, and only a trace amount of bromo-
barrier. Because of this reactivity pattern, a ruthenium-bound
cyclohexane was detected (Tables 1 and S2†). These results
alkoxide instead of alcohol is formed as an intermediate.
indicate that no freely diffusing alkyl radicals are formed in the
Then in the next step, proton transfer from Ru–OH to the
oxidation of cyclohexane by RuO4ꢀ in the presence of Ca2+ and/
alkoxide occurs via TS3(RuO4ꢀ) to generate the cyclohexanol
or AcOH.
product. Similar reaction pathways are observed for cyclo-
The kinetic isotope effects (KIE) for cyclohexane oxidation by
hexane oxidation by RuO4, except in this case no radical inter-
mediate (INT2) is formed (Fig. S11†). The reaction barrier
(DG298‡) is 17.8 kcal molꢀ1, consistent with the experimental
observation that RuO4 reacts readily with cyclohexane at room
temperature.
ꢀ
RuO4 under various conditions were determined by competi-
tive oxidation of an equimolar mixture of c-C6H12 and c-C6D12.
The KIE for RuO4ꢀ/Ca2+, RuO4ꢀ/AcOH and RuO4ꢀ/Ca2+/AcOH
were found to be 6.4 ꢃ 0.2, 13.9 ꢃ 0.4 and 6.5 ꢃ 0.2, respectively.
Such large KIEs are indicative of C–H bond cleavage in the rate-
limiting step.
In the oxidation of cyclohexane by RuO4ꢀ in the presence of
[Ca(OTf)]+, the reaction mechanism is similar. [Ca(OTf)]+ forms
an intermediate, INT1(CaOTf), with RuO4ꢀ; the Ca is bound to
two oxo ligands. Due to the electron withdrawing effects of Ca(II)
centre, the Ru–O bond lengths are changed from 1.740 (in
Baꢀsed on the experimental results, the oxidation of alkane by
RuO4 in the presence of Lewis acid (LA) appears to be
consistent with a mechanism that involves the initial binding of
LA to RuO4ꢀ to generate a precursor complex, which then reacts
with alkane via a H-atom abstraction/O-rebound mechanism to
generate the corresponding alcohol. Such a mechanism is
commonly accepted for C–H bond activation by cytochrome
P450 and various metal oxo species.30 However, since only
ketones are detected in the present case, this suggests that the
initially formed alcohol is rapidly oxidized to give the ketone.
This is supported by a competitive experiment involving the
oxidation of a mixture of cyclohexane and cyclopentanol (10:1)
by RuO4ꢀ/Ca2+, which resulted in the rapid and exclusive
formation of cyclopentanone (Fig. S10†). No alkene or products
derived from its oxidation were observed in the oxidation of
alkane by RuO4ꢀ/Ca2+, which rules out a dehydrogenation
mechanism that has been shown to occur in alkane oxidation by
non-heme iron(IV) oxo species.31 The binding of a Lewis acid to
ꢀ
˚
RuO4 , Table S3†) to 1.775 (oxo bound to Ca) and 1.709 A (free
oxo) in INT1(CaOTf). HAT from C6H12 then occurs via the
shorter and more electrophilic Ru]O bond. In this case there is
no cyclohexyl radical intermediate, INT2(RuO4ꢀ); HAT and
binding of cyclohexyl radical to a second oxo occur in a single
‡
step. The DG298 for the oxidation of cyclohexane by [RuO4(-
CaOTf)] (Fig. 7 and Table S3,† entry 3), via TS1(CaOTf), is
18.5 kcal molꢀ1. Such a lowering of 8.3 kcal molꢀ1 is in agree-
ment with the observed accelerating effect of Ca(II). We have
‡
also found the DG298 for the oxidation of cyclohexane by
[RuO4(Ca)]+ (Table S3,† entry 5) is higher than that by [RuO4(-
CaOTf)], so [RuO4(Ca)]+ should not be the active species in the
oxidation of cyclohexane.
ꢀ
In the presence of acetic acid, RuO4 is protonated to give
INT1(AcOH), [RuO3OH(AcO)/C6H12]. The AcOꢀ is held by two
ꢀ
RuO4 enhances its oxidizing power, as observed in non-heme
additional AcOH molecules through hydrogen bonding (struc-
iron(IV) oxo complexes32 and manganese oxo clusters.16,17
˚
tures given in Table S3†). The Ru–OH bond distance is 1.858 A;
protonation resuꢀlts in shortening of two of the Ru]O from
Theoretical calculations
˚
˚
1.740 A (in RuO4 ) to 1.709 A. HAT by INT1(AcOH) occurs via
In order to obtain further insights into the activating effects of one of the shorter and more electrophilic Ru]O; the resulting
Ca(II) and AcOH on RuO4ꢀ, the reaction mechanisms for the cyclohexyl radical then binds to Ru–OH/OAc to generate Ru
‡
oxidation of cyclohexane catalysed by RuO4ꢀ in the presence of bound cyclohexanol in the same step, INT2(AcOH). The DG298
Ca(OTf)2 and/or AcOH have been theoretically studied by for HAT from C6H12 to INT1(AcOH) via TS1(AcOH) is
density functional theory (DFT). As a comparison similar 15.2 kcal molꢀ1, which is signicantly lower than the DG298‡ for
ꢀ
studies with RuO4 have also been carried out.
RuO4 alone by 11.6 kcal molꢀ1, in accordance with the exper-
ꢀ
In the oxidation of cyclohexane by [RuO4]ꢀ in CH3CN (Fig. 7), imentally observed accelerating effects of AcOH on RuO4
.
cyclohexane and [RuO4]ꢀ rst form an intermediate,
In the presence of both [CaOTf]+ and AcOH, the intermediate
INT1(RuO4ꢀ), in which the two species are weakly attracted with RuO4ꢀ, INT1(CaOTf + AcOH), consists of AcOꢀ and Ca
together ([RuO4/C6H12]ꢀ). HAT then occurs from C6H12 to forming a chelate ring with Ru]O and Ru–OH, as well as three
Ru]O via a transition state TS1(RuO4ꢀ) to form a second H-bonded AcOH molecules (Fig. 7 and Table S3,† entry 4). The
intermediate, INT2(RuO4ꢀ). The reaction barrier (DG298‡) for free Ru]O bonds are further shortened to 1.692 A. Accordingly
˚
This journal is © The Royal Society of Chemistry 2020
Chem. Sci.

View Article Online
Chemical Science
Edge Article
Fig. 7 PESs for cyclohexane oxidation by [RuO4]ꢀ/[RuO4(AcOH)]ꢀ/[RuO4(CaOTf)]/[RuO4(AcOH)(CaOTf)] at the B3LYP level using LanL2TZ(f)
basis set (Ru) and 6–311++G(d,p) basis set (non-metals). Relative 298 K Gibbs free energies in acetonitrile are given in kcal molꢀ1. Not all acetic
acid molecules are shown for simplicity.
the DG298‡ for HAT from cyclohexane via TS1(CaOTf + AcOH) is acid such as Ca2+ or other group II metal ions, as well as a weak
lowered to 10.8 kcal molꢀ1, which is smaller than the value of Brønsted acid such as CH3CO2H. The addition of both Ca2+ and
18.5 kcal molꢀ1 and 15.2 kcal molꢀ1, respectively, with Ca(OTf)+ CH3CO2H generates a highly efficient system that can oxidize
or AcOH alone. This is in agreement with the observed coop- unactivated C–H bonds with much higher yields than the use of
erative activating effects of AcOH and Ca(II). HAT and binding of strong Lewis acids such as Sc3+ or BF3, with or without
the resulting cyclohexyl radical to a Ca-bound oxo ligand occur CH3CO2H. Such an observation may provide insights into the
in one step. Protonation by Ru–OH to the alkoxide then occurs design of active oxidants based on metal oxo species in
to generate cyclohexanol. The potential energy surfaces (PES) combination with relatively weak Brønsted and Lewis acids,
for RuO4/Ca(OTf)+, RuO4/AcOH and RuO4/Ca(OTf)+/AcOH are especially if the metal oxo or the substrate is sensitive to strong
‡
shown in Fig. S11.† The DG298 for HAT by RuO4 alone is acids. Our studies may also be relevant to oxidation by metal
17.8 kcal molꢀ1, consistent with the experimental observation oxo species in biological systems, where only mild Brønsted
that RuO4 is able to oxidize cyclohexane at ambient conditions. acids such as alkanoic or amino acids, and mild Lewis acids
There are little or no changes in the Ru]O distances of RuO4 such as Zn2+ or Ca2+, are present in cells. So may be highly
upon binding to Ca(OTf)+ and/or AcOH, and there are only efficient oxidizing systems can be generated in biological
small changes in the reaction barriers, in agreement with systems using this strategy.
experimental observations. This is in accordance with the Ru]
O bonds being highly electrophilic and non-basic, hence there
is little affinity for Lewis acids.
Conflicts of interest
There are no conicts to declare.
Conclusions
Acknowledgements
Our results demonstrate a remarkable cooperative effect of
a weak Brønsted acid and a weak Lewis acid on the activation of This work was supported by the Hong Kong Research Grants
a metal oxo species. RuO4ꢀ, although in high oxidation state of Council (CityU 11336816), the National Science Foundation of
+VII, is a weak oxidant due to stabilization by the four oxo China (21975043) and Guangdong Provincial Key Platforms and
ligands. However, it can be readily activated by a mild Lewis Major Scientic Research Projects for Colleges and Universities
Chem. Sci.
This journal is © The Royal Society of Chemistry 2020

View Article Online
Edge Article
Chemical Science
(2018KTSCX227). We thank Dr Hajime Hirao for very helpful 17 E. Y. Tsui and T. Agapie, Proc. Natl. Acad. Sci. U.S.A., 2013,
discussions.
110, 10084–10088.
18 M. M. Najafpour, T. Ehrenberg, M. Wiechen and P. Kurz,
Angew. Chem., Int. Ed., 2010, 49, 2233–2237.
19 M. Wiechen, I. Zaharieva, H. Dau and P. Kurz, Chem. Sci.,
2012, 3, 2330–2339.
20 S. Bang, Y.-M. Lee, S. Hong, K.-B. Cho, Y. Nishida, M. S. Seo,
R. Sarangi, S. Fukuzumi and W. Nam, Nat. Chem., 2014, 6,
934–940.
21 H. Du, Po-K. Lo, Z. Hu, H. Liang, K.-C. Lau, Y.-N. Wang,
W. W. Y. Lam and T.-C. Lau, Chem. Commun., 2011, 47,
7143–7145.
22 L. Ma, W. W. Y. Lam, P.-K. Lo, K.-C. Lau and T.-C. Lau,
Angew. Chem., Int. Ed., 2016, 55, 3012–3016.
23 T.-C. Lau and C.-K. Mak, J. Chem. Soc., Chem. Commun.,
1993, 766–767.
24 S.-M. Yiu, Z.-B. Wu, C.-K. Mak and T.-C. Lau, J. Am. Chem.
Soc., 2004, 126, 14921–14929.
25 S.-M. Yiu, W.-L. Man, X. Wang, W. W. Y. Lam, S.-M. Ng,
H.-K. Kwong, K.-C. Lau and T.-C. Lau, Chem. Commun.,
2011, 47, 4159–4161.
26 W. P. Griffith, Ruthenium Oxidation Complexes: Their Uses as
Homogenous Organic Catalysts, Springer, 2011.
27 W. P. Griffith, S. V. Ley, G. P. Whitcombe and A. D. White, J.
Chem. Soc., Chem. Commun., 1987, 1625–1627.
28 S. J. Hawkes, J. Chem. Educ., 1996, 73, 516.
29 E. A. Seddon and K. R. Seddon, The Chemistry of Ruthenium,
Elsevier, Amsterdam, 1984, vol. 52.
30 J. L. McLain, J. Lee and J. T. Groves, Biomimetic Oxidations
Catalyzed by Transition Metal Complexes. Imperial College
Press, London, 2000.
Notes and references
1 T. Devi, Y.-M. Lee, W. Nam and S. Fukuzumi, Coord. Chem.
Rev., 2020, 410, 213219.
2 Y. Liu and T.-C. Lau, J. Am. Chem. Soc., 2019, 141, 3755–3766.
3 S. Fukuzumi, Coord. Chem. Rev., 2013, 257, 1564–1575.
4 D. J. Vinyard, G. M. Ananyev and G. C. Dismukes, Annu. Rev.
Biochem., 2013, 82, 577–606.
5 J. Yano and V. Yachandra, Chem. Rev., 2014, 114, 4175–4205.
6 J. D. Blakemore, R. H. Crabtree and G. W. Brudvig, Chem.
Rev., 2015, 115, 12974–13005.
7 J. Barber, Chem. Soc. Rev., 2009, 38, 185–196.
8 Y. Umena, K. Kawakami, J.-R. Shen and N. Kamiya, Nature,
2011, 473, 55–60.
9 K. M. Davis, B. T. Sullivan, M. C. Palenik, L. Yan, V. Purohit,
G. Robison, I. Kosheleva, R. W. Henning, G. T. Seidler and
Y. Pushkar, Phys. Rev. X, 2018, 8, 041014.
10 Y. Pushkar, K. M. Davis and M. C. Palenik, J. Phys. Chem.
Lett., 2018, 9, 3525–3531.
11 W. W. Y. Lam, S.-M. Yiu, J. M. N. Lee, S. K.-Y. Yau,
H.-K. Kwong, T.-C. Lau, D. Liu and Z. Lin, J. Am. Chem.
Soc., 2006, 128, 2851–2858.
12 Y. Morimoto, H. Kotani, J. Park, Y.-M. Lee, W. Nam and
S. Fukuzumi, J. Am. Chem. Soc., 2011, 133, 403–405.
13 H. Yoon, H. Yoon, Y.-M. Lee, X. Wu, K.-B. Cho, R. Sarangi,
W. Nam and F. S. Fukuzumi, J. Am. Chem. Soc., 2013, 135,
9186–9194.
14 T. Devi, Y.-M. Lee, W. Nam and S. Fukuzumi, J. Am. Chem.
Soc., 2020, 142, 365–372.
15 T. Devi, Y.-M. Lee, W. Nam and S. Fukuzumi, J. Am. Chem.
Soc., 2018, 140, 8372–8375.
16 E. Y. Tsui, R. Tran, J. Yano and T. Agapie, Nat. Chem., 2013, 5,
293–299.
31 K.-B. Cho, X. Wu, Y.-M. Lee, Y. H. Kwon, S. Shaik and
W. Nam, J. Am. Chem. Soc., 2012, 134, 20222–20225.
32 W. Nam, Y.-M. Lee and S. Fukuzumi, Acc. Chem. Res., 2014,
47, 1146–1154.
This journal is © The Royal Society of Chemistry 2020
Chem. Sci.