Highly Efficient Oxidation of Secondary Alcohols to Ketones Catalyzed by Manganese Complexes of N4 Ligands with H2O2

Article abstract of DOI:10.1021/ol5032156

The manganese complex Mn(S-PMB)(CF₃SO₃)₂ was proven to be highly efficient in the catalytic oxidation of several benzylic and aliphatic secondary alcohols with H₂O₂ as the oxidant and acetic acid as the additive. A maximum turnover number of 4700 was achieved in the alcohol oxidation. In addition, the Hammett analysis unveiled the electrophilic nature of this manganese catalyst with N₄ ligand. (Chemical Equation Presented).

Full text of DOI:10.1021/ol5032156

Letter
pubs.acs.org/OrgLett
Highly Efficient Oxidation of Secondary Alcohols to Ketones
Catalyzed by Manganese Complexes of N4 Ligands with H2O2
Duyi Shen,†,‡ Chengxia Miao,† Daqian Xu,† Chungu Xia,† and Wei Sun*,†
†State Key Laboratory for Oxo Synthesis and Selective Oxidation, Lanzhou Institute of Chemical Physics, Chinese Academy of
Sciences, Lanzhou 730000, P. R. China
‡University of Chinese Academy of Sciences, Beijing 100049, P. R. China
S
* Supporting Information
ABSTRACT: The manganese complex Mn(S-PMB)(CF3SO3)2 was
proven to be highly efficient in the catalytic oxidation of several
benzylic and aliphatic secondary alcohols with H2O2 as the oxidant
and acetic acid as the additive. A maximum turnover number of 4700
was achieved in the alcohol oxidation. In addition, the Hammett
analysis unveiled the electrophilic nature of this manganese catalyst
with N4 ligand.
showed high activity and selectivity in the aerobic oxidation
of alcohols, mimicing galactose oxidase (GAO).8
everal nonheme enzymes are capable of realizing highly
Sefficient and selective oxidation for specific organic
substrates in vivo.1 To mimic these metalloenzyme functions,
many research groups have committed themselves to the
studies of biomimetic models, which generally consist of small
inorganic complexes.2 Faithful synthetic nonheme catalysts
were successfully demonstrated to be highly active in a serious
of oxidation reactions, such as the C−H oxidation of alkanes,3
epoxidation of olefins,4 and other oxidation reactions.
Specifically, the oxidation of alcohols to their respective
aldehydes and ketones is one of the fundamental trans-
formations; as such, classes of catalytic methods have already
been established.5 The seminal works of bioinspired complex-
catalyzed oxidation of alcohols were published in 1998 by Stack
et al.6 (Figure 1, ligands 1a−d) and Wieghardt et al.7 (Figure 1,
ligand 2), respectively. These groups’ copper complexes
Following these developments, diverse nonheme ligands and
their metal complexes were designed, synthesized, and applied
to the oxidation of alcohols. In 2001, Feringa et al.9 reported a
highly efficient and HOTf (OTf = CF3SO3)-accelerated alcohol
oxidation (up to 65% yield) catalyzed by a nonheme μ-oxo
diiron(III) complex with a N4Py-related pentadentate ligand
(Figure 1, ligands 3a and 3b). Meanwhile, Bauer et al.10
prepared a set of bi- and tridentate aminopyridine ligands and
corresponding iron complexes (Figure 1, ligand 4), which
showed catalytic activity in the oxidation of alcohols, including
especially the good chemical selectivity of secondary alcohols
over primary alcohols. With regard to the nature of iron-based
systems, a 2005 report from Nam et al.11 provided detailed
mechanistic insights into the oxidation of alcohol with in situ
generated oxoiron(IV) complexes bearing nonheme ligands
such as N4Py and TPA (Figure 1, ligands 3a and 5). Later, a
manganese complex, [Mn(BQEN)](OTf)2 (Figure 1, ligand 6),
was also proven to be an efficient catalyst in alcohol oxidation
with peracetic acid as the oxidant.12 The mechanistic
experiments predicted a metal-based mechanism rather than
auto-oxidation in this manganese system. Furthermore, the
oxidation of alcohol catalyzed by other catalytic nonheme
systems was reported, as were the mechanisms concerning
metal−oxo intermediates.13
Our group has dedicated the past few years to several
catalytic oxidations, particularly asymmetric epoxidation with
nonheme metal complexes as the catalysts. Notably, we found
that replacing the pyridines on ligands of S-PMPP14 (Figure 2,
L2) and MCP15 (Figure 2, L3) with benzimidazoles caused the
iron and manganese complexes with proline−benzimidazole-
based ligands (Figure 2, analogues of L1) to exhibit highly
Received: November 5, 2014
Figure 1. Selected structures of previously nonheme ligands.
© XXXX American Chemical Society
A
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Organic Letters
Letter
presence of 0.1 mol % of Mn(L1)(OTf)2 with 6 equiv of AA as
the additive (Table 1, entry 4). Reduction in the catalyst
loading led to a decreased yield (Table 1, entry 5). However,
extending the reaction time to 1 h established the optimized
conditions with full conversion and excellent yield with 0.05
mol % of catalyst and 1.5 equiv of H2O2 (Table 1, entry 6). It
should be noted that a moderate of yield was obtained even
with 0.01 mol % catalyst after 2 h, which underscored the
efficiency and stability of this manganese catalyst (TOF = 2 350
h−1 and TON = 4 700, respectively) (Table 1, entries 7 and 8).
However, under the optimized conditions, manganese com-
plexes coordinated with ligands L2 and L3 both showed poorer
activity, which likely demonstrates the advantages of
benzimidazole over the pyridine moiety14,16a of the nitrogen
ligands in some catalytic oxidations. Moreover, a variety of
oxidants always involved in biomimetic catalysis were
compared, and all showed inferiority to the “Mn(Ligand)-
(OTf)2-HOAc-H2O2” system (see the Supporting Information,
Table S1). Oxidative kinetic resolution of the secondary alcohol
was also observed with limited oxidant; unfortunately, the ee
value was still low (Table 1, entry 12).
After the optimized conditions were established, we oxidized
a variety of benzylic and aliphatic secondary alcohols to the
corresponding ketones. From the results listed in Table 2, good
to excellent yields were accomplished in most cases. For
example, the steric hindrance of the groups on the side chain
had an obvious impact and the activities decreased in the order
of Me > Et > i-Pr > t-Bu (Table 2, entries 1−4). For annular
benzylic secondary alcohols, the substrates were fully converted
but with the exception of partial benzylic C−H oxidation
products (Table 2, entries 5−7). However, in the oxidation of
diphenylmethanol, a 30% yield of benzophenone was produced
under the optimal conditions in Table 1. Unexpectedly, the
highest conversion and yield were achieved with the use of 14
equiv of AA18 (Table 2, entry 8), which was previously adopted
by Costas et al.19 and Talsi et al.20 in alkene epoxidation
catalyzed by manganese complexes of N4 ligands, respectively.
Similarly, for alcohols with a strong electron-withdrawing group
or heteroatom, we gained good yields of ketones (Table 2,
entries 9 and 10) with large amounts of AA. In the case of
substituted 1-phenylethanol, strong electron-donating groups
led to poor results, even under the condition B (Table 2,
entries 12 and 13). In the oxidation of the substrate-bearing
ester, the oxidation proceeds well with a 79% isolated yield
(Table 2, entry 14). In the case of allyl alcohol, both enone and
epoxyketone were obtained (Table 2, entry 15). To our delight,
generally good yields were reached only with 0.05 mol % of
manganese catalyst in the cases of both linear and cyclic
aliphatic secondary alcohols, which are sometimes thought of as
inactive substrates (Table 2, entries 16−21). However, the
steric effects was obvious in the example of 2-admantanol, and
larger amounts of catalyst and acid were needed (Table 2, entry
22). To explore the intramolecular chemoselectivity of
secondary over primary alcohols, we chose 1-phenyl-1,2-
ethanediol as the substrate and got a much higher selectivity
(83%) and isolated yield (78%) for secondary alcohol oxidation
than that of the iron system recently reported by Bauer et al.10b
In addition, intermolecular competition of secondary and
primary alcohols was also investigated (see the Supporting
Information). Likewise, the secondary alcohol was preferen-
tially converted to the ketone while the primary alcohol was
hardly oxidized in the present catalytic system.
Figure 2. Ligands studied in this work.
improved efficiencies and enantioselectivities in the asymmetric
epoxidation of various alkenes.16 Subsequent selective
oxidations of benzylic and aliphatic C−H bonds proved the
17
analogue catalyst Mn(S-PMB)(OTf)2 to be active and
superior to the analogue complexes with ligands of pyridine
moieties. These findings indicate a possibility that the
manganese catalyst could promote the oxidation of alcohols
even in a low catalyst loading. In an attempt to expand the
application of nonheme system, herein, we employed the
manganese complex Mn(S-PMB)(OTf)2 to the oxidation of a
series of secondary alcohols. To our delight, various alcohols
were oxidized to ketones with good to excellent yields. In
addition, the primary mechanisms, that is, the Hammett and
kinetic isotope effects (KIE), were also involved in this work.
First, we chose 1-phenylethanol as a model substrate to
screen the optimal conditions. As can be seen in Table 1,
almost no reaction occurred without manganese catalyst or
acetic acid (AA) (Table 1, entries 1 and 2). Afterward, the
substrate was fully converted to the acetophenone in the
a
Table 1. Screening Reaction Conditions
AcOH
z
time
(h)
GC conv
(%)
GC yield
(%)
entry complex x oxidant y
1
none (0)
H2O2
(1.3)
6
0
6
6
6
6
6
6
5
6
6
6
0.5
0.5
0.5
0.5
0.5
1
trace
trace
82
trace
trace
82
2
MnL1
(0.1)
H2O2
(1.3)
3
MnL1
(0.1)
H2O2
(1.3)
4
MnL1
(0.1)
H2O2
(1.5)
99
99
5
MnL1
(0.05)
H2O2
(1.5)
83
82
6
MnL1
(0.05)
H2O2
(1.5)
99
98
7
MnL1
(0.02)
H2O2
(1.5)
2
87
86
8
MnL1
(0.01)
H2O2
(1.5)
2
51
47
9
MnL1
(0.05)
H2O2
(1.5)
1
92
92
10
11
12
MnL2
(0.05)
H2O2
(1.5)
1
42
37
MnL3
(0.05)
H2O2
(1.5)
1
24
22
b
MnL1
(0.05)
H2O2
(0.8)
0.5
52
a
Reaction conditions: hydrogen peroxide (50% aqueous solution) with
0.5 mL of MeCN was delivered through syringe pump over 0.5−2 h to
a stirred solution of catalyst (0.01−0.1 mol %), acetic acid (0−6
equiv), internal standard (nitrobenzene), and substrate (0.5 mmol) in
1.0 mL of MeCN in the air at room temperature (entries 1−12).
b
Reaction at 0 °C for 0.5 h; 27% ee was observed.
B
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Letter
a
Table 2. Substrates Scope
a
Reaction conditions: hydrogen peroxide (50% aqueous solution) diluted with 0.5 mL of MeCN was delivered through a syringe pump over 1 h to a
stirred solution of catalyst, HOAc, internal standard (decane), and substrate (0.5 mmol) in 1.0 mL of MeCN in the air at room temperature.
b
c
d
Method A: catalyst (0.05 mol %), HOAc (6 equiv). Method B: catalyst (0.2 mol %), HOAc (14 equiv). Isolated yields are shown in parentheses.
e
f
g
h
Yield of 1H-indene-1,3(2H)-dione. Yield of naphthalene-1,4-dione. Yield of 7,8-dihydro-5H-benzo[7]annulene-5,9(6H)-dione. Oxiran-2-yl-
(phenyl)methanone.
In order to gain more insight into the alcohol oxidation, we
then investigated the influences of para-substituents on the
benzene ring. Therefore, competitive experiments of several
substituted 1-phenylethanol were carried out (see the
Supporting Information for details). The relative activities
(Krel values) were plotted against the para-substitutent constant
σ and an acceptable Hammett correlation was obtained. The
negative ρ value of −1.2 indicated the electrophilic nature of
this manganese catalyst, which conformed to the experimental
results.
competitive experiments due to the overlaps of peaks in GC for
1-phenylethanol and its deuterated alcohol (see the Supporting
Information for details). The KIE for this manganese-catalyzed
oxidation of secondary alcohol was 2.1, which seemed to be
consistent with that of the [Mn(BQEN)]2+ reported by Nam et
al. (KIE 2.2)12 and in situ [Mn(TPEN)]2+ complex reported by
Feringa et al. (KIE 2.2)21 in the oxidation of benzyl alcohol.
Combined with the excellent selectivity for acetophenone, it
may be concluded that the hydroxyl radical was not likely
involved in the process while a high-valent Mn−oxo species
might have been an active intermediate in this catalytic system.
In addition, acetic acid may play a key role in the activation of
Then the primary KIE value was determined, and 1-(4-
chlorophenyl)ethanol was selected as the mediation in the
C
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In summary, we exhibited a highly efficient biomimetic
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ASSOCIATED CONTENT
* Supporting Information
■
S
Experimental procedures, characterization data, and NMR
copies. This material is available free of charge via the Internet
at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
■
*E-mail: wsun@licp.cas.cn.
Notes
The authors declare no competing financial interest.
(14) Wang, B.; Miao, C.; Wang, S.; Kuhn, F. E.; Xia, C.; Sun, W. J.
̈
ACKNOWLEDGMENTS
We thank the National Natural Science Foundation of China
(Nos. 21133011 and 21373248) for financial support.
Organomet. Chem. 2012, 715, 9−12.
■
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J. 2012, 18, 6750−6753. (b) Wang, B.; Wang, S.; Xia, C.; Sun, W.
Chem.Eur. J. 2012, 18, 7332−7335.
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