Highly efficient oxidation of alcohols catalyzed by a porphyrin-inspired manganese complex

Article abstract of DOI:10.1039/c5cc03657g

A novel strategy for catalytic oxidation of a variety of benzylic, allylic, propargylic, and aliphatic alcohols to the corresponding aldehydes or ketones by an in situ formed porphyrin-inspired manganese complex in excellent yields (up to 99%) has been successfully developed.

Full text of DOI:10.1039/c5cc03657g

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DOI: 10.1039/C5CC03657G
Journal Name
COMMUNICATION
Highly efficient oxidation of alcohols catalyzed by a porphyrin-
inspired manganese complex
Wen Dai,a Ying Lv,a Lianyue Wang,a Sensen Shang,a Bo Chen,a Guosong Lia and Shuang Gao*a
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
www.rsc.org/
A novel strategy for catalytic oxidation of a variety of benzylic,
allylic, propargylic, and aliphatic alcohols to the corresponding
aldehydes or ketones by an in situ formed porphyrin-inspired
manganese complex in excellent yields (up to 99%) has been
successfully developed.
The selective oxidation of alcohols to carbonyl compounds is
among the most important and extensively used class of
oxidation reactions in organic synthesis.1 The past decades have
witnessed significant progress in the catalytic methods for
oxidation of alcohols with organocatalysts or metal-based
catalysts which offer economic and environmental benefits
over traditional stoichiometric oxidants.2 Owing to
metalloenzyme-catalyzed reactions usually exhibiting exquisite
substrate specificity and operating under mild conditions,
widespread interest has been directed toward the development
of bioinspired or biomimetic alcohol oxidation methods.3 Since
the initial breakthrough accomplished in oxidation of alcohols
using copper complex miming the galactose oxidase (GAO) by
Stack et al. and Wieghardt et al. in 1983,1e, 4 other bioinspired or
biomimetic catalytic systems have also been developed and
selective oxidation of a broad range of alcohols has been
achieved.5 However, only limited examples of oxidation of
alcohols based on metalloporphyrins, which are the mimics of
the cytochrome P450 active site, have been previously
described and refined to find application in industrial and fine-
chemical synthesis.6 This unfortunate situation is mainly
attributed to notoriously difficult synthesis of porphyrin ligands.
We recently developed a new type of porphyrin-inspired N4
ligands which were easily prepared, structurally diverse,
sterically and electronically tunable as well as fulfilled the
structural requirements of the porphyrin ligand in some way.7
The porphyrin-inspired ligands which possess excellent
tolerance for oxidation reactions have been successfully applied
in asymmetric epoxidation of olefins and asymmetric
sulfoxidation.7-8 Meanwhile, manganese-catalyzed oxidation of
Scheme 1 Strategy for the development of oxidation of alcohols method.
alcohols should offer many remarkable advantages, as
manganese is abundant, easily available and relatively nontoxic
and shows variable oxidation state.9 With this background in
mind, it was envisioned that we could develop a highly effective,
selective, and broad-scope catalyst system for oxidation of
alcohols exploring the manganese in combination with the
porphyrin-inspired N4 ligands (Scheme 1). We disclose herein a
porphyrin-inspired manganese catalyst system that enables
selective oxidation of benzylic, allylic, propargylic and aliphatic
alcohols to the corresponding aldehydes or ketones in high
yields (up to 99%). High chemoselectivity, mild conditions and
easy scalability make this catalyst system highly practical.
Initially, we chose cinnamyl alcohol 1a as the model substrate
to examine the effect of carboxylic acid (CA). The reactions were
conducted with 1a (0.2 mmol), CA (1.0 equiv), H2O2 (4.0 equiv)
and 2.5 mol% of catalyst which was generated from Mn(OTf)2
o
and L4, in acetonitrile at 0 C. When the acetic acid was used,
the corresponding cinnamaldehyde 2a was obtained in 24%
yield (Table 1, entry 1). Replacing the acetic acid with a wide
variety of aliphatic acids including branched and cyclic
carboxylic acid led a significant improvement in yield (entries 2–
9). Among them, the adamantane carboxylic acid (aca) provided
the best result (entry 9). In addition to the aliphatic acids, the
aromatic carboxylic acids were also tested and compatible with
our catalyst system with high yield (entries 10 and 11).
Subsequently, the oxidant loading was examined. We found
that 6 equiv of H2O2 were necessary in order to achieve the best
result (entries 12 and 13). After testing CA loading, the amount
a.Dalian Institute of Chemical Physics, the Chinese Academy of Sciences and Dalian
National Laboratory for Clean Energy, Dalian 116023, China. Email:
sgao@dicp.ac.cn
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 1
† Footnotes relating to the title and/or authors should appear here.
Electronic Supplementary Information (ESI) available: Experimental procedures
and compound characterization data. See DOI: 10.1039/x0xx00000x
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Table 1 Screening of the identity and amount of additives.
Table 2 Investigation of effect of ligand structure.
View Article Online
DOI: 10.1039/C5CC03657G
entry
1
2
additive
CH3COOH
H2O2 (equiv.)
yield(%)a
24
4
4
36
entry
1
2
ligand
L1
% yielda
55
3
4
4
4
44
56
L2
85
3
4
L3
L5
L6
L7
L8
L2
L2
73
37
56
84
52
86
74
5
6
4
4
48
31
5
6
7
4
56
7
8b
9c
8
9
4
4
4
42
60
46
aDetermined by GC. bMn(OTf)2 (1.0 mol%), L2 (1.0 mol%). cMn(OTf)2 (0.5
mol%), L2 (0.5 mol%).
10
electron-donating and -withdrawing substituents at the
aromatic ring proceeded well to give the corresponding
acetophenone derivatives in good to excellent yields (entries 6–
9). For annular benzylic secondary alcohols, the substrates
could be successfully oxidized into the desired product in
excellent yield (entries 10–13). Excellent yield was preserved for
the oxidation of benzylic secondary alcohols bearing condensed
aromatic ring and sterically hindered structure (entries 14–15).
In the case of alcohol bearing electron-withdrawing group, only
moderate yield was obtained (entry 16). Alcohols containing
heterocycles could also serve as good substrate and afford the
corresponding ketones in good yield (entries 17–19). When the
reactions of aliphatic secondary alcohols including linear and
cyclic alcohols were carried out, the ketones were formed in
moderate yield (entries 20–22). In addition to the secondary
alcohols, the primary benzylic alcohols were also investigated.
Gratifyingly, good yield was also achieved (entries 23–24). To
further explore the generality of the current catalyst system, we
investigated the oxidation of propargylic alcohols. The reaction
of the secondary propargylic alcohols provided the
corresponding ketones in moderate to excellent yields (entries
25–27). Meanwhile, the excellent yield was obtained for the
oxidation of the terminal alkyne 1-phenyl-2-propyn-1-ol (entry
28). The present system was also applicable to the primary
propargylic alcohol, although the yield was moderate (entry 29).
To investigate the intramolecular chemoselectivity of secondary
over primary alcohol, 1-phenyl-1,2-ethanediol was chosen as
the substrate. Moderate yield was obtained for the oxidation of
the secondary alcohol and no trace of aldehyde was observed
which indicated our catalyst system possessed high
chemoselectivity for secondary alcohols (entry 30). Finally, the
11
4
49
12
13
14b
15c
aca
aca
aca
aca
6
8
6
6
76
78
75
65
aDetermined by GC. baca (50 mol%). caca (30 mol%).
of CA was successfully lowered to 50 mol% with no decrease of
yield (entry 14). Further reducing the CA loading to 30 mol%
resulted an obvious decrease in yield (entry 15).
Further examinations were focused on ligand screening.
From the evaluation of various ligands containing oxazoline
moieties derived from chiral amino alcohol, we identified L2 as
the ligand providing the best result (Table 2, entries 1–7). It is
noteworthy that decreasing the amount of catalyst to 1.0 mol%
failed to bring about deterioration of yield (entry 8). Remarkably,
further lowering the catalyst loading to 0.5 mol% resulted a
significant decrease in yield (entry 9). Finally, the ratio of
Mn(OTf)2 and L2 was investigated. Best result was obtained
with a ratio of 1:1. (see the supporting information, Table S1).
With the optimal conditions in hand, exploration of substrate
scope was carried out, and the results were summarized in
Table 3. A variety of conjugated allylic alcohols were smoothly
converted into their corresponding a,β-unsaturated aldehyde
or ketones with excellent yields (entries 1–4). The unconjugated
allylic alcohol 1-Octen-3-ol was less reactive, affording the
corresponding ketone in 34% yield (entry 5). The catalyst
system was next applied to oxidation of benzylic primary and
secondary alcohols. 1-Arylethanols with
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Table 3 Substrate scope
Table 3 Substrate scope (Contd.)
View Article Online
DOI: 10.1039/C5CC03657G
entry
25
substrate
product
% yielda
70
entry
1
substrate
product
% yielda
86b
2
92
26
91
3
4
5
99b
88b
34b
27
28
58b
85
6
95
29
30
40
56
7
84
8
9
87
70
aIsolated yields. bDetermined by GC.
successful results of oxidation of alcohols prompted us to
further explore the oxidative kinetic resolution of racemic
alcohols. Unfortunately, only low to moderate ee value was
obtained (see the supporting information, Table S2).
To gain insight into the nature of active oxidant, competitive
oxidation of p-substituted 1-phenylethanol were performed
under the optimized conditions. We found good linear
correlation between the log (kX/kH) and σp+ with negative ρ+ = -
0.38 which demonstrated that transition state of the reaction
was electron-demanding and the active oxidant was
electrophilic (Fig. 1).5g, 10 Then the KIE for this manganese-
catalyzed oxidation of 1-Phenylethanol was 3.0, which was
basically consistent with that of the manganese-catalyzed
10
11
92
86
12
13
90
93
14
15
16
90
89
48
alcohols oxidation reported by Nam et al. (KIE 2.2) and Sun et al.
5g
(KIE 2.1).5f,
Moreover, the current catalyst system has
excellent selectivity for the oxidation of alcohols to the
corresponding aldehydes or ketones. It may be inferred from
these results that a high-valent Mn-oxo species would be an
active intermediate in current catalyst system and carboxylic
acid additive may play a key role in the activation of H2O2 to
form the high-valent Mn-oxo species, although the exact
structure of the catalyst is not clear.
17
18
80
90
To further evaluate the practical utility of the catalyst system,
the oxidation of 1-(4-methoxyphenyl)ethanol 1b and xanthydrol
1c was carried out on gram scale under the optimized
conditions, affording the desired product 2b and 2c in 90% yield
and 88% yield after a prolonged reaction time, respectively
(Scheme 2).
19
88
20
21
41b
38b
0.3
0.2
0.1
0
p-OMe
22
23
25b
74
p-Me
p-H
24
75
-0.1
-0.2
-0.3
p-CF3
y = -0.3766x - 0.0116
R² = 0.9977
+
-0.4
-0.9
0.1
0.6
σp
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Fig. 1 Hammett plots of Log (kX/kH) vs σp+ for the oxidation of para-substituted 1-
phenylethanol.
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In summary, we have successfully developed a highly efficient
and general catalytic oxidation of alcohols method that employs
an inexpensive and easily available porphyrin-inspired
manganese complex, allowing for the oxidation of a wide
variety of benzylic, allylic, propargylic and aliphatic alcohols to
corresponding aldehydes or ketones in high yields. Mild
conditions, high chemoselectivity, and easy scalability make this
catalyst system highly practical. Moreover, Hammett analysis
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This work was financially supported by the NSFC (21403219)
and the dedicated grant for new technology of methanol
conversion from Dalian Institute of Chemical and Physics,
Chinese Academy of Science is gratefully acknowledged.
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