Highly efficient and practical aerobic oxidation of alcohols by inorganic-ligand supported copper catalysis

Article abstract of DOI:10.1039/c9gc01248f

The oxidation of alcohols to aldehydes or ketones is a highly relevant conversion for the pharmaceutical and fine-chemical industries, and for biomass conversion, and is commonly performed using stoichiometric amounts of highly hazardous oxidants. The aerobic oxidation of alcohols with transition metal complex catalysts previously required complicated organic ligands and/or nitroxyl radicals as co-catalysts. Herein, we report an efficient and eco-friendly method to promote the aerobic oxidation of alcohols using an inorganic-ligand supported copper catalyst 1, (NH₄)₄[CuMo₆O₁₈(OH)₆], with O₂ (1 atm) as the sole oxidant. Catalyst 1 is synthesized directly from cheap and commonly available (NH₄)₆Mo₇O₂₄·4H₂O and CuSO₄, which consists of a pure inorganic framework built from a central Cu^II core supported by six Mo^VIO₆ inorganic scaffolds. The copper catalyst 1 exhibits excellent selectivity and activity towards a wide range of substrates in the catalytic oxidation of alcohols, and can avoid the use of toxic oxidants, nitroxyl radicals, and potentially air/moisture sensitive and complicated organic ligands that are not commercially available. Owing to its robust inorganic framework, catalyst 1 shows good stability and reusability, and the catalytic oxidation of alcohols with catalyst 1 could be readily scaled up to gram scale with little loss of catalytic activity, demonstrating great potential of the inorganic-ligand supported Cu catalysts in catalytic chemical transformations.

Full text of DOI:10.1039/c9gc01248f

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DOI: 10.1039/C9GC01248F
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ARTICLE
Received 00th January
20xx,
Highly Efficient and Practical Aerobic Oxidation of Alcohols
by Inorganic-ligand Supported Copper Catalysis
a,
a,
‡
Zheyu Wei, Shi Ru, Qixin Zhao,a, Han Yu,a,b,* Gang Zhangc,* and Yongge Weib,*
‡
‡
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
www.rsc.org/
The oxidation of alcohols to aldehydes or ketones is a highly relevant conversion for the pharmaceutical and fine-chemical
industries and for biomass conversion, which is commonly performed using stoichiometric amounts of highly hazardous
oxidants. The aerobic oxidation of alcohols with transition metal complexes catalysts previously required complicated
organic ligands and/ or nitroxyl radicals as the cocatalysts. Herein, we report an efficient and eco-friendly method to
promote the aerobic oxidation of alcohols using an inorganic-ligand supported copper catalyst 1, (NH4)4[CuMo6O18(OH)6],
with O2 (1 atm) as the sole oxidant. Catalyst 1 is synthesized directly from cheap and commonly available (NH4)6Mo7O24
·4H2O and CuSO4, which consists of a pure inorganic framework built from a central CuII core supported by six MoVIO6
inorganic scaffolds. The copper catalyst 1 exhibits excellent selectivity and activity towards a wide range of substrates in
the catalytic oxidation of alcohols, and can avoid the use of toxic oxidants, nitroxyl radicals, potentially air/moisture
sensitive and complicated organic ligands that are not commercially available. Owing to the robust inorganic framework,
catalyst 1 shows good stability and reusability, and the catalytic oxidation of alcohols with catalyst 1 could be readily
scaled up to gram-scale with little loss of catalytic activity, demonstrating a great potential of the inorganic-ligand
supported Cu catalysts in catalytic chemical transformations.
OH
R2
O
catalysis
O2
R1
R1
R2
1 Introduction
Previous work
A) Organic-Noble-Metal Catalysis
The selective oxidation of alcohols to aldehydes or ketones is
one of the most important and challenging transformations in
the synthesis of fine chemicals1. Traditionally, such
transformations have been performed with stoichiometric
oxidants, including MnO2, chromium(VI) salts, “activated
DMSO” methods and hypervalent iodine reagents, which need
expensive, environmentally hazardous chemicals and are only
suitable for use on a small scale2. From both environmental
and economic aspects, there is an urgent need for more
efficient methods that employ clean oxidants such as O2 and a
recyclable catalyst. In light of this, over the last three decades,
a number of groups have developed effective catalyst systems
for aerobic alcohol oxidation based on coordination complexes
of noble metals including Pd3and Ru4(Figure 1A); however, the
high cost of noble metals and the use of ligands that are not
commercially available limits their applications.
SO3Na
SO3Na
(Py)Pd(OAc)2
RuCl2(PPh3)3/TEMPO
O
N
N
Ar
Ar
Pd(OAc)2/
N
RO2C Pd CO2R
OH2
Py =
N
TEMPO
N
N
Sigman
Uemura
Sheldon
Sheldon
B) Organic-Cu and/or nitroxyl radical catalysis
(bpy)Cu(OTf)/TEMPO(AZADO)/NMI
O
(bpy)CuBr2/TEMPO/KOtBu
N
N
N
N
N
bpy
bpy
N
O
N
N
O
N
TEMPO
AZADO
NMI
TEMPO
Stahl
Sheldon
(Phen)CuCl/DBAD/NMI/K2CO3
(bpy)Cu(OTf)2/TEMPO/DBU
O
N
BuOt
N
N
N
O
N
N
N
OtBu
N
NMI
N
N
phen
DBAD
DBU
bpy
Koskinen
Markó
This work
C) Inorganic-ligand Supported Cu Catalysis
First-row transition metals have a tendency to undergo a
O
Mo
O
O
Mo
O
(NH4)4
(NH4)4[CuMo6O18(OH)6]
O
O
O
O
O
O
Organic ligand and Nitroxyl radical free
Recyclable
O
O
O
O
Cu
O
Mo
O
Mo
O
a. School of Chemical and Environmental Engineering Shanghai Institute of
Technology,No. 100 Haiquan Road, Shanghai 201418 (P.R. China) E-mail:
hanyu0220@tsinghua.edu.cn
O
O
Mild conditions in water
Broad substrate scope
Mo
O
Mo
O
O
O
O
b. Key Lab of Organic Optoelectronics & Molecular Engineering of Ministry of
Education, Department of Chemistry, Tsinghua University, Beijing 100084, P.R.
China. E-mail: yonggewei@ tsinghua.edu.cn
Figure 1 Representative Organic-Metal Catalyst Systems and
Inorganic-ligand supported Cu-catalyst 1
facile ligand exchange, and data from various studies suggest
aerobic alcohol oxidation catalysts derived from these metals
possess broader functional group tolerance (e.g., Cu5, 6, Co7,
Fe8, and V9). Recently, organo-copper catalyst systems,
c. Institute of Materials Science & Technology Analytical & Testing Center
Sichuan University, Chengdu 610064(P.R. China). E-mail: gangzhang@scu.edu.cn
‡These authors contributed equally to this work.
*All correspondences should be addressed.
†Electronic Supplementary Information (ESI) available: experimental conditions,
supplementary table and NMR spectra. See DOI: 10.1039/x0xx00000x
This journal is © The Royal Society of Chemistry 20xx
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particularly those employing nitroxyl radicals such as TEMPO
or dialkylazodicarboxylate as redox-active co-catalysts
corresponding aldehydes or ketones using O2 as the sole
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oxidant in a solvent mixture of acetonitDriOleI: a10n.d103w9a/Cte9Gr C(F0i1g2u48reF
1C). This catalyst exhibits high catalytic efficiency and
possesses excellent stability throughout the catalytic cycle.
Compared with organic-copper/nitroxyl radical catalyst
systems, the inorganic-ligand supported copper catalysts
provide significant advantages over traditional oxidation
procedures in that they are robust to auto-oxidation, can be
recovered easily, and avoid the use of complicated/sensitive
organic ligands and expensive nitroxyl radicals.
a
(Figure 1B), have emerged as some of the most effective
catalysts for the aerobic oxidation of alcohols to aldehydes or
ketones. Such reagents are compatible with activated allylic,
benzylic, propargylic and unactivated (aliphatic) alcohols, and
their chemoselectivity and functional-group compatibility
challenges traditional alcohol oxidation methods10. However, a
serious deficiency of both systems is that they require
relatively large amounts of organic ligands which are
expensive, toxic, air/moisture sensitive and not commercially
available. In addition, they also rely upon significant quantities
of nitroxyl radicals (5-10 mol%) as co-catalysts, commonly the
most expensive component of the catalyst system; this
becomes a serious concern for industrial-scale applications.
Furthermore, the established protocols that employ Cu-base
catalysts rely on the use of environmentally detrimental
halogenated solvents.
The use of water as a solvent and/or co-solvent leads to
both decreased reaction rates and catalyst deactivation11. It
would be of considerable benefit, i.e., safer, cheaper, and
more environmentally benign if alcohol oxidation processes
could be performed in water or a mixture of water and organic
solvents due to its natural abundance and inherently greener
characteristics12. Therefore, there is significant demand for the
development of more sustainable and environmentally
friendly alcohol oxidation catalyst strategies which employ
molecular oxygen as the terminal oxidant in water or a mixture
system.
Polyoxometalates (POMs) 13, 14, as a class of metal-oxide
clusters with unmatched molecular structural diversity and
functionality, exhibit high redox and acidic properties at the
atomic and molecular levels as well as resistance toward
hydrolysis and oxidative degradation. They thus offer great
potentials as stable inorganic ligands for coordination with
metal ions, differing from classical transition-metal complexes
of organic ligands15. Very recently, our group reported firstly
that the Anderson-type POMs16 can be used as the inorganic-
ligand supported metal catalysts for highly efficient aerobic
oxidation of aldehydes to carboxylic acids in water, or the
oxidation of amines to imines under mild conditions17. This
type of metal catalysts possess unique structures bearing six
MoVIO6 inorganic scaffolds that is supported by a central metal
atom; this kind of structure greatly enhances the Lewis acidity
of the catalytically active sites and as well as enabling the
edge-sharing MoO6 unit to act as ligands analogous to those
employed in traditional organometallic complexes. These
properties make POMs ideal candidates for solving those
problems associated with the instability and activity of
catalysts commonly used in organic-metal catalysis, and thus
provides a potential alternative for the aerobic oxidation of
alcohols. Herein, we report an inorganic-ligand supported
copper catalyst 1, (NH4)4[CuMo6O18(OH)6]18 (Figure 1C.), which
possesses a copper(II) ion core supported by six MoVIO6
inorganic scaffolds. The catalyst 1 can be readily synthesized in
one simple step in aqueous solution at 100°C (see supporting
information, Figures S1 to S3), and can efficiently catalyze the
oxidation of various aromatic and aliphatic alcohols to
2 Results and discussion
Initially, our studies began with the oxidation of piperonyl
alcohol as a model substrate using the copper catalysts 1 and
one atmospheric pressure O2 as the sole oxidant at 60 °C
(Table S1). No product was detected in the absence of
catalysts 1 over 24 h. Gratifyingly, water was found to be a
suitable solvent for the oxidation of piperonyl alcohol with the
desired product being obtained in 72% yield and >99%
selectivity within 24 h, which commonly inhibits reactivity in
organic-copper/ nitroxyl radicals system when is employed as
a co-solvent. Acetonitrile - being the best solvent for organic-
copper/ nitroxyl radicals systems - also provided the desired
product in 66% yield with >99% selectivity over 10h. With
regards to others solvents, dioxane, DMF and DMSO all proved
to be ineffective except the DCM (60% yield with 99%
selectivity). When the reaction was carried out using
acetonitrile as the solvent, the oxidation of piperonyl alcohol
proceeded much slower because of poor solubility of the
catalyst 1 in this reaction medium. Not surprisingly, when
acetonitrile was employed as a co- solvent (a solvent mixture
of acetonitrile and water, v/v=1:1), the oxidized product was
obtained in 90% yield within 12 h. The ratio of
water/acetonitrile in the mixed solvent system was
investigated and an increase in the proportion of water had no
effect on the reaction efficiency (Table S2). The addition of
additives can influence the reaction apparently (Table 1,
entries 1-21). Among those tested, salts bearing the chloride ion
gave the highest conversion to the corresponding aldehyde (>99%)
with excellent yield (99%) after 12 h at 60 °C; this is most likely due
to the Cl− acting as an electron-transfer mediator to improve the
electron transfer efficiency. Subsequently, the counterion effect of
inorganic chloride on the oxidation was investigated. In addition to
+
NH4 , other cations including K+, Rb+, Cs+, Mg2+, Ca2+, Zn2+and Li+
proved to be ineffective (Table 1, entries 10-15). When 18-crown-6
was used in combination with NaCl, the reaction became much
slower, showing the obvious effect of the cation (Table S3).
Furthermore, in consideration of the aldehyde being easily oxidized
further to the corresponding acid, the reactions under the standard
conditions was monitored, and none of the over-oxidized product
was formed (Table S4). Furthermore, the impact of the catalyst
loading and reaction temperature were investigated. Lowering the
loading of 1 from 1 mol% to 0.5 or 0.1 mol% resulted in the
aldehyde product being obtained in 92% and 90% reduced yield,
respectively (Table 1, entries 16 and 17).
2 | J. Name., 2012, 00, 1-3
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Table 1 Optimization of reaction conditionsa
The superior aerobic oxidation efficiency of the comVbieinweAdrticclaetOanlylinset
platform indicates that every constituent plays a vital role in the
inorganic-ligand supported copper catalysis.
DOI: 10.1039/C9GC01248F
Cat.1
(1.0 mol%)
O
O
Additive (10 mol%)
O
O
OH
O
O2 (1 atm)
(balloon)
H2O/CH3CN =1/1(2 ml)
60 oC, 12h
Table 2 Oxidation of activated alcohols a,b
1
Cat. (1.0 mol %)
Con.(%)c/Sel.(%)b
OH
R'
Cat.
Additive
Yield
Entry
O
NaCl (10 mol%)
O2 (1 atm)
(balloon)
+
(%)c
70
R
H2O/CH3CN =1:1 (2.0 ml)
60 oC, T h
R
R'
(mmol%)
1
(10mmol%)
Na2CO3
1
97/86
95/83
69/39
99/98
48/19
70/65
>99/99
87/93
83/90
92/97
85/93
85/90
99/99
27/52
22/82
19/95
26/97
99/99
98/99
90/99
95/97
94/96
<5/<5
R, R' = benzyl, alkyl, H
2
1
Na2SO4
NaHSO3
NaClO4
NaHSO4
NaF
46
3
1
<10
92
O
O
O
X
4
1
R
X
6
7
8
9
X = F, 20h, 87% (95%)
X = Cl, 20h, 90% (87%)
X = Br, 24h, 91% (88%)
X = NO2, 20h, 82% (80%)
10
11
12
X =F, 16h, 93% (90%)
X = Br, 16h, 90% (87%)
X = OH, 15h, 96% (92%)
2
3
4
5
R = H, 15h, 95% (91%)
5
1
16
R = CH3, 13h, 99% (96%)
R = OCH3, 12h, 99% (95%)
R = CH(CH3)2, 18h, 97%(92%)
6
1
18
7
1
NaCl
NaBr
NaI
99
O
O
O
O
S
O
O
8
1
69
OH
O
13
14
15
16
9
1
65
13h, 96% (92%)
15h, 98% (92%)
20h, 87% (81%)
16h, 96%(90%)
10
11
12
11
12
13
14
15
16
17
18d
19e
20f
21g
1
KCl
72
O
O
Br
O
O
O
O
1
RbCl
62
NH2
Br
X
1
CsCl
68
19
20
21
22
23
24
X = H, 16h, 95% (89%)
X = CH3, 14h, 99% (93%)
X = F, 18h, 95% (86%)
X = Cl, 18h, 92% (83%)
X = NO2 18h, 90%(85%)
18
17
20h, 92% (90%)
18h, 99% (92%)
16h, 95% (82%)
1
NH4Cl
CaCl2
MgCl2
ZnCl2
LiCl
95
1
<10
<5
<5
<10
92
O
O
O
1
O
1
O
1
25
26
27
28
20h, 96% (88%)
18h, 93% (90%)
12h, 97% (92%)
24h, 97% (88%)
0.5
0.1
1
NaCl
NaCl
NaCl
NaCl
NaCl
NaCl
O
O
90
O
S
O
O
N
83
X
34
1
87
35
18h, 96% (85%)
33
29
30
31
32
X = H, 12h, 94% (90%)
X = CH3, 16h, 98% (89%)
X = OCH3, 18h, 99% (87%)
X = Cl, 18h, 92% (80%)
20h, 95% (80%)
18h, 96% (83%)
1
80
1
<5
O
O
O
O
S
N
aReaction conditions: Cat. 1 (1.0 mol%), alcohols (1.0 mmol), O2 (1
atm), additives (10 mol%) and MeCN/H2O=1/1 (2 mL) at 60oC.
Unless otherwise noted. Selectivity were determined by GC and
confirmed by GC-MS. Yields and conversion were calculated from
1H NMR spectra. dat 25 °C. at 70 °C. Reactions were carried out
under atmospheric air. gReactions were carried out under nitrogen
atmosphere.
37
24h, 93% (83%)
36
22h, 98% (89%)
38
24h, 97% (91%)
b
c
aReaction conditions: Cat. 1 (1.0 mol%), alcohols (1.0 mmol), O2
(1 atm), NaCl (10 mol%) and MeCN/H2O=1/1 (2 mL) at 60oC.
bYields were determined by GC-MS analysis of the crude reaction
mixtures, values in parentheses are the isolated yields.
e
f
Because the structure of POMs is pH dependent, the oxidation
selectivity was also tested at different pH values. The desired
product was obtained in good yield and with good selectivity when
the pH of the reaction medium was in the range of 5-9; moving out
of this region significantly reduced both the conversion and
selectivity (Figure S7) due to the decomposition of catalyst 1 in
strongly acidic or basic solution.
Using the optimized reaction conditions, we explored the
substrate scope of this catalytic oxidation system. On the basis of
our initial efforts to obtain high selectivity for the alcohol oxidation,
the oxidation of aromatic alcohols bearing various functional groups
was examined. (Table 2). All substituted benzyl alcohols with
electron-donating and electron-withdrawing groups were easily
oxidized into the corresponding aldehydes or ketones with excellent
selectivity (compounds 2-28). Electron-donating substituents on
Altering the reaction temperature led to a significant decrease in
the yields of the aldehyde product (Table 1, entries 18 and 19).
While optimized conditions employed one atmosphere of O2, the
reaction can also be conducted in air, albeit requiring a prolonged
reaction time (Table 1, entry 20). When the reaction was performed
under nitrogen atmosphere, the desired product was obtained in
<5% yield (Table 1, entry 21), showing that O2 is an essential oxidant
for the reaction. It should be noted that CuSO4, Na2MoO4 or
(NH4)6Mo7O24·4H2O = (NH4)6[MoMo6O18(O)6] ·4H2O ( which is also
considered to be an isomerized Anderson-structured POM with an
Mo core instead of Cu as the central atom) when used as the
catalyst alone, provided only trace amounts of product even with a
prolonged reaction time up to 24 h. Yet, when a mixture of 1.0
mol% of CuSO4 and 1.0 mol% of the (NH4)6Mo7O24 was used as the
catalyst, the desired product can be obtained in a low yield of 37%.
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 3
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the phenyl group accelerated the reaction, while reactions of place of NaCl as the additive, affording an increase in aldehyde
View Article Online
DOI: 10.1039/C9GC01248F
alcohols with electron-withdrawing groups required longer reaction yields from 27 to 95% (Table S5). The selective oxidation of linear
times. It is worth noting that primary benzylic alcohols can be
aliphatic alcohols proceeded smoothly giving the corresponding
products in excellent yields (compounds 39-45). A series of
functionalized alcohols, linear aliphatic alcohols bearing chloro,
thioether and amide groups, could all be oxidized chemoselectively
to afford the corresponding aldehydes or ketones with excellent
yields (compounds 46-49). Furthermore, N-protecting groups, such
as Cbz, was tolerated, and substrates bearing these groups were
oxidized in excellent yields under the standard conditions
(compounds 50).
Table 3 Oxidation of primary and secondary unactivated alcoholsa
1
Cat. (1.0 mol %)
OH
R'
Na2SO3 (10 mol%)
O
O2 (1 atm)
(balloon)
+
R
R
R'
H2O/CH3CN =1:1 (2.0 ml)
60 oC, T h
R, R' = alkyl, H
O
O
O
n
O
5
Alcohols with an isolated C=C double bond or with a C=C double
bond conjugated to the hydroxyl group, such as hex-5-enal, (E)-
pent-2-enal and (Z)-3,7-dimethylocta-2,6-dienal, were all amenable
39
40
n = 2, 6h, 93%
7, 8h, 92%
42
9h, 91%
43
8h, 95%
41
5h, 93%
O
n
O
S
O
O
Cl
to the reaction conditions with the oxidation
proceeding
O
4
O
quantitatively or nearly quantitatively (compounds 51 and 52).
Alcohols with a terminal C−C triple bond could also be oxidized to
aldehydes or ketones in excellent yields (compounds 53 and 54).
Annular unactivated alcohols can also undergo facile oxidation
to the corresponding aldehydes or ketones. Single ring alcohols
underwent oxidation to give the corresponding ketones in almost
quantitative yields (compounds 55 and 56). Sterically hindered
polycyclic alcohols can also be oxidized in high yields to the
corresponding aldehydes and ketones (compounds 57 and 58).
Heterocyclic alcohols containing a ctertiary amine underwent
efficient oxidation in excellent yields (compounds 59).
To further demonstrate the practicality of this catalytic system,
a 50 mmol reaction of benzyl alcohol was conducted using pure O2
to give 4.7754g of benzaldehyde in 90% isolated yield with 99%
selectivity within 24h (SchemeS1). These results suggest that in the
case of reaction systems using a low catalyst loading of 1, high
activity, selectivity, and practicability can be achieved for the
aerobic oxidation of alcohols. Next, the ability of the catalyst 1 to be
recycled and used in successive reactions was also evaluated. The
solid catalyst was isolated by filtration and reused directly for the
subsequent oxidation of benzyl alcohol without further purification
(precipitation of catalyst after adding ether to the reaction system).
The catalyst 1 could be used at least six times without any
degradation in catalyst performance (Figure S7). To confirm the
high stability of the catalyst and its associated performance, the
structure and morphology of the catalyst was further investigated
using FTIR and XRD. The structure and morphology of the recycled
catalyst remains unchanged from its original state (see supporting
information, Figures S9 and S10).
47
48
,
12h 97%
44
45
n = 1, 6h, 92%
3, 6h, 98%
46
12h, 93%
,
12h 96%
O
NHCbz
O
O
N
H
49
50
8h, 95%
,
12h 92%
O
O
O
3
O
3
n-C6H13
51
54
12h 92%
52
53
6h, 95%
O
,
15h, 96%
,
9h 95%
O
O
O
N
n
55
56
n = 2, 8h, 94%
3, 15h, 99%
59
57
58
,
15h 95%
,
16h 90%
,
8h 93%
aReaction conditions: Cat. 1 (1.0 mol%), alcohols (1.0 mmol), O2
(1 atm), Na2SO3 (10 mol%) and MeCN/H2O=1/1 (2 mL) at 60oC.
bYields were determined by GC-MS analysis of the crude reaction
mixtures.
quantitatively oxidized to the corresponding aldehydes. Compared
with primary benzylic alcohols, secondary benzylic alcohols are less
reactive. For unsaturated aromatic alcohols, cinnamyl alcohol,
bearing a carbon-carbon double bond, provided excellent yields of
the corresponding products (compounds 29-32). The reactions
display functional-group compatibility similar to that observed with
heteroaromatic alcohols, including tolerance of sulfur, oxygen and
nitrogen atoms, such as pyridin-2-ylmethanol/1-(pyridin-2-yl)ethan-
1-ol, thiophen-2-ylmethanol/1-(thiophen-2-yl)ethan-1-ol, furan-2-
ylmethanol/1-(furan-2-yl)ethan-1-ol, with which organometallic
catalyst systems generally cannot effect the catalytic oxidation of
these alcohols because of strong coordination to the metal center,
could also be transformed into the corresponding aldehydes or
ketones almost in quantitative yields (compounds 33-38).
The high reactivity of the substituted activated alcohols
prompted us to employ our methodology for the selective oxidation
of more challenging linear and cyclic unactivated aliphatic alcohols
(Table 3). However, linear alcohols, such as octan-1-ol, gave low
selectivities for the corresponding aldehydes owing to an
overoxidation to form the carboxylic acid under the standard
conditions. This problem was circumvented by using Na2SO3 in
In order to ascertain the mechanism of the reaction, a number
of control experiments were conducted. When Cu-POM catalyst 1
was used stoichiometrically under an inert atmosphere, trace
amounts of benzyl alcohol are converted into benzaldehyde,
indicating that catalyst 1 is not as an oxidant （ FigureS8 Aa ） .
When 1.0 mmol Cu-catalyst 1 is used under an O2 atmosphere at
o
60 C for 2 hours, the Cu catalyst 1 activates molecular oxygen to
afford an active species B, which undergoes O-O bond heterolysis
to give metal-oxo species C (the ESI-MS analysis showed m/z
1246(M + 23) peaks attributed to B and m/z 1230 (M+ 23) peaks
attributed to C, Figure S8 Ab and Ac, Figure S11 and S12 ). Next, the
combination of metal-oxo species C and a stoichiometric amount of
benzyl alcohol react under an inert atmosphere, with benzaldehyde
4 | J. Name., 2012, 00, 1-3
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obtained in 90% yield. This confirms that metal-oxo species C is the hydrogen peroxide (detected by GC-MS) and the CuPOM-catalyzed
View Article Online
active catalyst.
reactions more closely resemble galactose DoOxiId: 1a0s.e11093,9i/nC9wGhCic0h12C48uFII
Two types of deuterium kinetic isotope effects were measured and a hydroxyl radical operate jointly as the one-electron oxidant to
for the oxidation of PhCH2OH (Figure S8B), including independent mediate a two electron alcohol oxidation reaction; in galactose
rate measurements for the oxidation of RCH2OH and RCD2OH oxidase, a single Cu center reacts with O2 to afford H2O2 as a
(Figure S8B b), and intramolecular competition experiments (Figure byproduct. The highly reactive Cu-oxo species C then reacts with
S8B a). Each of these studies provides unique insights into the the alcohol to give the intermediate D, followed by H-atom
reaction mechanism. The oxidations of PhCHDOH reveal a large abstraction to produce the aldehyde and regenerate E. Finally, the
kinetic isotope effect for the C-H cleavage step, kH/kD = 7.09. intermediate E (CuII) is oxidized by hydrogen peroxide back to
Measurement of the independentrates for the oxidations of species A (Cu1).
PhCH2OH and PhCD2OH showed no significant isotope effect (kH/kD
= 1.06). These data show that C-H cleavage is not turnover limiting
in the oxidation of PhCH2OH.
4 Conclusions
The cyclic voltammograms of catalyst 1/NaCl (1:10) in
a
In summary, we have developed a highly efficient inorganic-
ligand coordinated copper-catalyst system for the oxidation of
alcohols to aldehydes or ketones. The catalyst system exhibits a
wide alcohol substrate tolerance (more than 59 substrates,
including primary and secondary allylic, benzylic, and aliphatic) with
excellent selectivity and recoverability. The oxidation reaction is
carried out under mild reaction conditions in water. This catalytic
system takes operational simplicity into account and avoids using
any organic ligand and nitroxyl radical, which is beneficial for its
practical use in pharmaceuticals, fragrances, and food additives.
The method of improving the activity and selectivity of a catalytic
reaction by picking the additives was first introduced into the
polyoxometalate catalyzed oxidation of alcoholic systems, which is
of great significance both academically and industrially. The
generality of this methodology gives it the potential to be used on
an industrial scale.
H2O/CH3CN(1:1) solvent system shows two oxidative waves at –0.25
V and +0.47 V versus Fc/Fc+ (Fc, ferrocene). We assign these
features to the CuI/ CuII and the MoV/MoVI couples, respectively.
These waves are both quasireversible and at relatively low
potentials, suggesting that a CuI/CuII cycle is possible with this
ligand system.
(MoVI)POMCuI
O2
A
OH
O2
R1 R2
(MoV)POMCuII
(MoVi)POMCuII(O2)
E
O
B
(MoVI)POMCuII
Catalyst 1
R1 R2
H2O
+
R2
R1
H
H2O
H2O2
O
(MoVI)POMCuII
(MoVI)POMCuII
Conflicts of interest
OH
D
C
OH
There are no conflicts to declare.
OH
Acknowledgements
R1 R2
This work was supported by the National Natural Science
Foundation of China (Nos. 21871183, 21631007, 21471087,
21225103), Doctoral Fund of Ministry of Education of China No.
20130002110042, Tsinghua University Initiative Foundation
Research Program No. 20131089204, the State Key Laboratory of
Natural and Biomimetic Drugs K20160202 and Shanghai Natural
Science Foundation of China (No.18ZR1437900).
Figure 2 Proposed mechanism for the Cu-catalyzed oxidation of
alcohols
Based on these experimental results, a tentative mechanism for
the oxidation of alcohols has been proposed (Figure 2). For the
inorganic-ligand supported copper catalyst 1, the two oxidizing
equivalents required for oxidation are not only stored at the copper
center but are also delocalized on the six edge-sharing MoO6 units.
The Cu-POM catalyst 1 reaction with alcohol to generate an active
species A, and the A and E are a pair of isomers that can be
converted to each other, this may be via the transfer of electrons
through an intramolecular oxygen bridge, Cu-O-Mo, to an inorganic
ligand, MoO6 where one of the Mo unit changes from a positive
hexavalent species to a positive pentavalent species. The Cu-POM A
first activates molecular oxygen to generate an active species B.
Subsequently, the species B undergoes O = O bond heterolysis to
give the highly reactive metal-oxo species C as active oxidants.
During this process, water participates in the reaction to produce
Notes and references
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DOI: 10.1039/C9GC01248F
(NH4)4
O
O
Mo
O
O
O
O
O
Mo
O
O
O
O
O
O
O
Cu
O
Mo
Mo
O
O
O
O
Mo
O
Mo
O
O
O
O
1:
Cu
(NH4)4[ Mo6O18(OH)6]
1
Cat. (1.0 mol %)
O
OH
R2
NaCl or Na2SO3 (0.1eq.)
59 examples
up to 99% yield
O2 (1 atm)
(balloon)
+
R1
R2
R1
H2O/CH3CN =1:1 (2.0 ml)
50 oC or 60 oC, 6-24 h
R1, R2 = alkyl, H
An inorganic ligand supported copper catalyst which can effectively catalyze the aerobic oxidation
of alcohols to afford aldehydes or ketones with excellent selectivity and yields.