Revisiting Alkane Hydroxylation with m-CPBA (m-Chloroperbenzoic Acid) Catalyzed by Nickel(II) Complexes

Article abstract of DOI:10.1002/chem.202102532

Mechanistic studies are performed on the alkane hydroxylation with m-CPBA (m-chloroperbenzoic acid) catalyzed by nickel(II) complexes, Ni^II(L). In the oxidation of cycloalkanes, Ni^II(TPA) acts as an efficient catalyst with a high yield and a high alcohol selectivity. In the oxidation of adamantane, the tertiary carbon is predominantly oxidized. The reaction rate shows first-order dependence on [substrate] and [Ni^II(L)] but is independent on [m-CPBA]; v_obs=k₂[substrate][Ni^II(L)]. The reaction exhibited a relatively large kinetic deuterium isotope effect (KIE) of 6.7, demonstrating that the hydrogen atom abstraction is involved in the rate-limiting step of the catalytic cycle. Furthermore, Ni^II(L) supported by related tetradentate ligands exhibit apparently different catalytic activity, suggesting contribution of the Ni^II(L) in the catalytic cycle. Based on the kinetic analysis and the significant effects of O₂ and CCl₄ on the product distribution pattern, possible contributions of (L)Ni^II?O^. and the aroyloxyl radical as the reactive oxidants are discussed.

Full text of DOI:10.1002/chem.202102532

Evaluation Only. Created with Aspose.PDF. Copyright 2002-2021 Aspose Pty Ltd.
Accepted Article
Accepted Article
Title: Revisiting Alkane Hydroxylation with m-CPBA
(mChloroperbenzoic Acid) Catalyzed by Nickel(II) Complexes
Authors: Shinobu Itoh, Tomoya Shinke, Mayu Itoh, Takuma Wada,
Yuma Morimoto, Sachiko Yanagisawa, Hideki Sugimoto, and
Minoru Kubo
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Chem. Eur. J. 10.1002/chem.202102532
Link to VoR: https://doi.org/10.1002/chem.202102532
01/2020

Evaluation Only. Created with Aspose.PDF. Copyright 2002-2021 Aspose Pty Ltd.
10.1002/chem.202102532
Chemistry - A European Journal
FULL PAPER
Revisiting Alkane Hydroxylation with m-CPBA (m-
Chloroperbenzoic Acid) Catalyzed by Nickel(II) Complexes
Tomoya Shinke,[a] Mayu Itoh,[a] Takuma Wada,[a] Yuma Morimoto,[a] Sachiko Yanagisawa,[b]
Hideki Sugimoto,[a] Minoru Kubo,[b] and Shinobu Itoh*[a]
[a]
[b]
T. Shinke, M. Itoh, T. Wada, Assist. Prof. Y. Morimoto, Assoc. Prof. H. Sugimoto, Prof. S. Itoh
Department of Molecular Chemistry, Division of Applied Chemistry
Graduate School of Engineering, Osaka University
2-1 Yamadaoka, Suita, Osaka 565-0871, Japan
E-mail: shinobu@chem.eng.osaka-u.ac.jp
Twitter:@Shinoumls
Assoc. Prof. S. Yanagisawa, Prof. M. Kubo
Graduate School of Science, University of Hyogo
3-2-1 Koto, Kamigori-cho, Ako-gun, Hyogo 678-1297, Japan
Supporting information for this article is given via a link at the end of the document.
Abstract: Mechanistic studies are performed on the alkane
hydroxylation with m-CPBA (m-chloroperbenzoic acid) catalyzed by
nickel(II) complexes, NiII(L). In the oxidation of cycloalkanes, NiII(TPA)
acts as an efficient catalyst with a high yield and a high alcohol
selectivity. In the oxidation of adamantane, the tertiary carbon is
active-oxygen species have been invoked as the key reactive
intermediates based on the spectroscopic and DFT studies.[5]
In contrast to the large number of iron- and copper-active-
oxygen complexes reported over the past decades, relatively few
examples of such active-oxygen complexes of nickel have been
explored.[6] Nonetheless, Schwarz and co-workers demonstrated
that NiO+ is an efficient oxidant for methane hydroxylation
compared to FeO+ and MnO+ in the gas phase reaction,[7] which
is afterwards supported by theoretical calculations by Yoshizawa
and co-workers.[8] In this respect, we have demonstrated that
nickel(II)-complexes, NiII(L), supported by tripodal N4 ligands such
as tris(2-pyridylmethyl)amine (TPA) and its analogues can
catalyze oxygenation of alkanes by m-chloroperbenzoic acid (m-
CPBA) in solution, where the yield of alcohol product and its
selectivity (alcohol/ketone, A/K) are much better than those of the
Fe- and Mn-complexes supported by the same ligand (TPA)
(Scheme 1).[9] Afterwards, we and other groups investigated the
catalytic alkane hydroxylation reaction by m-CPBA using a variety
of nickel(II) complexes to examine the ligand effects on the
catalytic activity.[10] Regarding to the reactive intermediate
involved in the catalytic reaction, (L)Ni–O• (oxyl) species have
been postulated based on the product analysis.[10g]
predominantly oxidized.
The reaction rate shows first-order
dependence on [substrate] and [NiII(L)] but is independent on [m-
CPBA]; vobs = k2[substrate][ NiII(L)]. The reaction exhibited a relatively
large kinetic deuterium isotope effect (KIE) of 6.7, demonstrating that
the hydrogen atom abstraction is involved in the rate-limiting step of
the catalytic cycle.
Furthermore, NiII(L) supported by related
tetradentate ligands exhibit apparently different catalytic activity,
suggesting contribution of the NiII(L) in the catalytic cycle. Based on
the kinetic analysis and the significant effects of O2 and CCl4 on the
product distribution pattern, possible contributions of (L)NiII–O• and
the acyloxyl radical as the reactive oxidants are discussed.
Introduction
Alkanes are the most abundant chemicals obtained from crude oil
and natural gas. In the present chemical industry and synthetic
organic chemistry, selective hydroxylation of alkanes (saturated
hydrocarbons) is an important chemical process to obtain
valuable compounds such as alcohols, which themselves are also
important precursors for the synthesis of various organic
compounds.[1] Thus, the selective alkane hydroxylation has long
been one of the most important research objectives in catalytic
chemistry.[2] In nature, metalloenzymes such as cytochrome
P450 and methane monooxygenases (MMOs) catalyze the
hydroxylation of alkanes having strong C–H bonds (BDE ~100
kcal/mol) using molecular oxygen (O2) as an oxidant with great
efficiency and high alcohol-product selectivity under very mild
conditions.[3] Such metalloenzymes contain iron or copper at their
active sites, and for that reason, a large number of iron- and
copper-active-oxygen (superoxide, peroxide, oxyl radical, and
oxide) intermediates have been studied extensively in model
systems.[4] More recently, iron- and copper-loaded zeolites have
been demonstrated to be efficient catalysts for selective oxidation
of methane to methanol, in which similar types of iron- and copper-
NiII(L) / m-CPBA
R–H
R–OH
Scheme 1. Alkane hydroxylation with m-CPBA catalyzed by nickel(II)-
complexes.
Meanwhile, Hartwig and co-worker conducted detailed
mechanistic studies on the NiII(L)-catalyzed alkane oxidation
reaction by m-CPBA to propose a free-radical chain mechanism
shown in Scheme 2.[11] In this mechanism, the reaction of m-
CPBA and NiII(L) generates ArC(O)O• (aroyloxyl radical, Ar = 3-
chlorophenyl) as an active oxidant for the hydrogen atom
abstraction (HAA) from the alkane substrates (R–H) giving m-CBA
(m-chlorobenzoic acid) and radical intermediate of the substrate
(R•). Then, the generated substrate radical R• reacts with another
m-CPBAmolecule to give the alcohol product R-OH and ArC(O)O•,
making the catalytic cycle.
considered as an initiator of the radical chain reaction to generate
In this mechanism, NiII(L) is
1
This article is protected by copyright. All rights reserved.

Evaluation Only. Created with Aspose.PDF. Copyright 2002-2021 Aspose Pty Ltd.
10.1002/chem.202102532
Chemistry - A European Journal
FULL PAPER
ArC(O)O• from m-CPBA, but does not directly participate to the
C–H bond activation process of R–H. However, little was
discussed how ArC(O)O• was generated from the reaction of m-
CPBA and NiII(L), and fate of the nickel complex afterwards.
95.7 kcal/mol (Cy8H),[13] indicating that the C–H bond activation
of the substrates is involved in the alcohol formation process as
discussed later based on the kinetic analysis. Notably, the
product yield reached 95 % based on the oxidant (m-CPBA) in the
case of Cy8H (entry 3), demonstrating that most of m-CPBA was
used for the substrate oxidation. The chlorinated products (CynCl)
were also obtained, suggesting that cycloalkyl radical (Cyn•) is
generated by hydrogen atom abstraction from the substrate by the
active oxidant. Generated Cyn• may react with the solvent
molecule (CH2Cl2) to give CynCl. In fact, bromocyclohexane
(Cy6Br) was obtained instead of Cy6Cl, when the reaction was
carried out in CH2Br2/CH3CN.
O
H
R
Ar
OH
m-CBA
O
O
NiII(L)
OH
R•
Ar
m-CPBA
(Ar = 3-chlorophenyl)
O
Ar
O
Table 1. Hydroxylation of cycloalkanes (CynH) with m-CPBA catalyzed by
NiII(TPA) under anaerobic condition (N2) for 2 h.
OH
Cl
O
Cl
O
NiII(TPA): 0.36 mM
m-CPBA: 180 mM
m-CPBA
R
OH
O
+
+
+
+
under N2 at 30 ºC for 2 h
CH2Cl2/CH3CN (3:1)
1~3
1~3
1~3
1~3
1~3
Scheme 2. Hartwig’s mechanism.
CynCl
PhCl
L
A
K
In this study, we revisited our alkane hydroxylation by m-CPBA
with NiII-complexes supported by TPA and related tripodal
tetradentate ligands to get deeper insights into the catalytic
mechanism.
Yield (%) based on m-CPBA [a]
CynH
A/(K+L)[c]
A
K
L
1.2
-
CynCl Total[b] PhCl
1
2
3
4
5
Cy6H
Cy7H
58
48
84
9.0
9.4
8.8
6.0
4.8
3.6
3.8
4.8
2.2
1.6
1.4
1.6
83
62
95
36
37
34
30
5.8
8
Results and Discussion
Cy8H
-
26
18
Alkane Hydroxylation with m-CPBA Catalyzed by NiII(TPA)
Cy6H[d]
Cy6H[d,e]
9.2
1.2
0.70
We have previously reported an efficient alkane hydroxylation by
m-CPBA
catalyzed
by
nickel(II)
complex
of
TPA,
[NiII(TPA)(OAc)(H2O)](OAc) (NiII(TPA)) (Figure 1).[9] Here, we re-
examined the oxidation of cycloalkanes (CynH: Cy6H,
cyclohexane; Cy7H, cycloheptane; Cy8H: cyclooctane) by m-
CPBA in the presence of a catalytic amount of NiII(TPA) (Table 1).
9.4
1.2
0.77
Reaction conditions: [NiII(TPA)] = 0.36 mM, [m-CPBA] = 0.18 M, [Cy6H] = 2.7
M, [Cy7H] = 2.4 M, [Cy8H] = 2.2 M in CH2Cl2/CH3CN (v/v =3/1) at 30 ºC for 2 h
under N2. [a] The yields were determined by GC-FID using calibration curves of
the products. [b] Total yield = A + 2K + 2L + CynCl. [c] Alcohol product
selectivity. [d] The reaction was carried out under O2. [e] PPh3 (2 equiv against
m-CPBA) was added after the reaction.
OAc
N
N
OAc
Generation of Cyn• (substrate radical) was also confirmed by
the reaction carried out under O2 atmosphere (Table 1, entry 4).
In the anaerobic reaction of Cy6H (under N2), A was obtained as
the major product and the alcohol-product selectivity was quite
high (entry 1). In this reaction, PhCl derived from m-CPBA was
also generated in a relatively high yield (34 %). On the other hand,
when the oxidation of Cy6H was carried out under O2 atmosphere
(entry 4), the product distribution pattern differed significantly from
that of the anaerobic reaction under otherwise the same
conditions. Namely, total yield of the oxidation products (A + K +
L + Cy6Cl) as well as the yield of PhCl decreased significantly.
Furthermore, the alcohol product selectivity A/(K + L) was
completely lost. The result suggests that the radical intermediate
is trapped by O2 to induce “Russell rearrangement” (termination
of radical chain reaction) (Scheme 3). Namely, generated
cyclohexyl radical intermediate (Cy6•) via the hydrogen atom
abstraction from Cy6H by a reactive oxidant rapidly reacts with O2
at a rate of ~109 M–1 s–1 to generate cyclohexyl peroxy radical
species (Cy6OO•).[14] Radical coupling between two Cy6OO•
generates tetroxide Cy6OOOOCy6, which is eventually converted
to A and K in an equal amount.[15] The reaction solution was
analysed by GC-FID after addition of PPh3 to get almost the same
result to that of the aerobic reaction (entry 5). This result
Ni
N
OH2
N
Figure 1. The structure of [NiII(TPA)(OAc)(H2O)](OAc) (NiII(TPA)).
The reaction was started by adding m-CPBA (180 mM) to a
CH2Cl2/CH3CN (v/v =3/1) solution containing a catalytic amount of
NiII(TPA) (0.36 mM) and an excess amount of CynH (2.2~2.7 M)
at 30 ºC under anaerobic conditions (N2). After 2 h, the yields of
alcohol (A), ketone (K), lactone (L), chlorocycloalkane (CynCl) and
chlorobenzene (PhCl, decarboxylation product of ArC(O)O•) were
determined by GC-FID. As shown in Table 1, NiII(TPA) acted as
an efficient catalyst to give A as the major product together with
K as a minor product (entries 1–3). A small amount of L (ε-
caprolactone), generated from K via Baeyer-Villiger reaction by
m-CPBA, was also detected in the case of Cy6H (entry 1).
However, the corresponding L was hardly detected in the cases
of Cy7H and Cy8H (entries 2 and 3), since Baeyer–Villiger reaction
of cyclohexanone was reported to be much faster than that of
cycloheptanone and cyclooctenone.[12] In this case, the alcohol
product selectivity (A/(K + L)) increased as 5.8 → 8 → 18 as the
bond dissociation energy of the C–H bond of the substrates
decreases as 97.7 kcal/mol (Cy6H) → 96.5 kcal/mol (Cy7H)
→
2
This article is protected by copyright. All rights reserved.

Evaluation Only. Created with Aspose.PDF. Copyright 2002-2021 Aspose Pty Ltd.
10.1002/chem.202102532
Chemistry - A European Journal
FULL PAPER
suggested that Cy6OO• was not converted to cyclohexyl hydrogen
peroxide (Cy6OOH) or cyclohexyl peroxide (Cy6OOCy6). If such
peroxide products were formed in the aerobic reaction, A should
be a major product after the treatment with PPh3.[11]
clearly indicating that the hydrogen atom abstraction (HAA) is
involve in the rate-limiting step of the catalytic cycle.
25
20
15
10
5
140
120
100
80
40
30
20
10
0
(a)
(b)
(c)
O O
O
O O
H
O
O2
O
O
x 2
H
O
60
HO
H
40
20
0
0
0
0.5 1.0 1.5 2.0 2.5 3.0
[Cy6H] / M
80 100 120 140 160 180 200 220
0
0.05
[NiII(TPA)] / mM
0.10
0.20
0.15
Scheme 3. Russel rearrangement of tetroxide.
[m-CPBA] / mM
Figure 3. Kinetic analysis on the catalytic hydroxylation of cyclohexane (Cy6H)
with m-CPBA in the presence of a catalytic amount of NiII(TPA). (a) Plots of vobs
against the substrate concentration; [Cy6H] = 0.5–2.7 M, [m-CPBA] = 180 mM,
[NiII(TPA)] = 0.036 mM. (b) Plots of vobs against the catalyst concentration;
[Cy6H] = 2.7 M, [m-CPBA] = 180 mM, [NiII(TPA)] = 0.036–0.18 mM, (c) Plots of
vobs against the oxidant concentration; [Cy6H] = 2.7 M, [m-CPBA] = 80–220 mM,
[NiII(TPA)] = 0.036 mM. (c). All reactions were conducted at least three times in
CH2Cl2/CH3CN (v/v = 3/1) under N2 at 30 ºC.
Hydroxylation of adamantane by m-CPBA also proceeded
efficiently to give the corresponding alcohols, 3A in 34 % and 2A
in 5 %, together with a small amount of ketone 2K (2.6 %)
(Prefixes 3 and 2 represent tertiary and secondary, respectively.
The yields are calculated based on m-CPBA.) (Figure 2). As has
been reported,[9] the regioselectivity of the tertiary carbon (3º)
against the secondary carbon (2º) was quite high (3º/2º = 13),
suggesting that the reactive intermediate is not a highly reactive
free radical species such as OH• as suggested by Hartwig et al.[11,
Catalytic Activity of Other Ni-complexes
16]
In our previous study, we examined the catalytic activity of the NiII-
complexes supported by a series of tetradentate ligands having
one, two, or three 2,4-di-tert-butyl phenol group(s) (L1tBuH, L2tBuH2,
and L3tBuH3, Figure 4) in the oxidation of Cy6H by m-CPBA.[10a, 10b]
To get further insights into the reaction mechanism, catalytic
activities of these NiII-complexes were re-examined.
OH
NiII(TPA): 0.36 mM
m-CPBA: 180 mM
OH
+
O
+
under N2 at 30 ºC for 2 h
CH2Cl2/CH3CN (3:1)
0.27 M
3A
2A
2K
Figure 2. Hydroxylation of adamantane with m-CPBA catalyzed by NiII(TPA)
in CH2Cl2/CH3CN (v/v =3/1) under anaerobic conditions (N2) for 2h.
tBu
tBu
tBu
tBu
N
tBtu
Bu
O
O
Kinetic Analysis
N
OAc
H
N
Ni
O
N
OAc
NiII
NiII
O
N
OMe
H
N
OAc
TMG
Kinetic analysis on the oxidation of Cy6H was performed to get
further insights into the catalytic mechanism. The reaction rates
(vobs) were obtained from the linear plots of the amounts of
products (A + K + L, M) against the reaction time (s) at the initial
stage (0 – 20 min) of the catalytic reaction using a lower
concentration condition of the catalyst ([NiII(TPA)] = 0.036 – 0.18
mM). Figures S1(a), S1(b), and S1(c) show the plots obtained by
changing the concentration of Cy6H, NiII(TPA), and m-CPBA,
respectively. In all cases, the product amounts increased linearly,
from which the observed reaction rates (vobs, M s–1) were
determined as the slopes. Then, the rate-dependences on the
concentrations of Cy6H, NiII(TPA), and m-CPBA were plotted as
shown in Figure 3(a), 3(b), and 3(c), respectively. Apparently, the
H
OH
tBu
O
H
tBu
tBu
tBu
tBu
tBu
tBu
NiII(L1tBu
)
NiII(L2tBu
)
NiII(L3tBu
)
Figure 4. NiII-complexes supported by phenol(ate) ligands. TMG is 1,1,3,3-
tetramethylguanidine. The syntheses and structural characterizations of these
NiII-complexes were reported in our previous papers.[10a, 10b]
In Figure 5 is shown the plots of product amounts against the
reaction time for each complex in the oxidation of Cy6H, and the
amounts of products obtained after 15 min and the observed
reaction rates (vobs, M s–1) are summarized in Table S1. In these
cases as well, A was obtained as the major product together with
K, L, and Cy6Cl as the minor products. Apparently, reactivity of
the four complexes was different (vobs = 23 x 10–6 M s–1 for
NiII(TPA); 32 x 10–6 M s–1 for NiII(L1tBu); 14 x 10–6 M s–1 for
NiII(L2tBu); 6.0 x 10–6 M s–1 for NiII(L3tBu)) and the monophenol
reaction rate (vobs) exhibits first-order dependence on the
concentrations of both Cy6H and NiII(TPA) (Figures 3(a) and 3(b))
but was independent on the concentration of m-CPBA (Figure
3(c)) under the reaction conditions employed (see figure captions
of Figure 3). Thus, the reaction rate can be expressed by eq (1),
where k2 was calculated as 0.22 M–1 s–1.
2.5
TPA
L1tBu
L2tBu
2.0
vobs = k2[Cy6H][NiII(TPA)]
(1)
L3tBu
1.5
The results indicate that m-CPBA itself is not involved in the
turnover-limiting step (TLS) of the catalytic reaction. Thus, if the
Hartwig mechanism (Scheme 2) operates, the reaction of R• and
m-CPBA must be much faster than the reaction between
ArC(O)O• and R–H giving m-CBA and R•.
1.0
0.5
0
0
400
800
1200
time / s
Catalytic hydroxylation of Cy6D (C6D12) was also examined
under the same reaction conditions to obtain the second-order
rate constant k2 as 3.3 x 10–2 M–1 s–1 (Figure S2). Thus, the kinetic
deuterium isotope effect, k2(Cy6H)/k2(Cy6D), was obtained as 6.7,
Figure 5. Plots of the product amounts against the reaction time in the catalytic
hydroxylation of Cy6H (2.7 M) with m-CPBA (180 mM) catalyzed by NiII-
complexes (0.036 mM) in CH2Cl2/CH3CN (v/v
= 3/1) under N2 at room
temperature. (30 ºC).
3
This article is protected by copyright. All rights reserved.