Cu-NHC-TEMPO catalyzed aerobic oxidation of primary alcohols to aldehydes

Article abstract of DOI:10.1021/jo401252d

Imidazolium salts bearing TEMPO groups react with commercially available copper powder affording Cu-NHC complexes. The in situ generated Cu-NHC-TEMPO complexes are quite efficient catalysts for aerobic oxidation of primary alcohols into aldehydes. The catalyst is easily available, and various primary alcohols were selectively converted to aldehydes in excellent yields.

Full text of DOI:10.1021/jo401252d

Subscriber access provided by Georgetown University | Lauinger and Blommer Libraries
Article
Cu-NHC-TEMPO Catalyzed Aerobic
Oxidation of Primary Alcohols to Aldehydes
Xiaolong Liu, Qinqin Xia, Yuejiao Zhang, Wanzhi Chen, and Congyan Chen
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/jo401252d • Publication Date (Web): 14 Aug 2013
Downloaded from http://pubs.acs.org on August 18, 2013
Just Accepted
“Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted
online prior to technical editing, formatting for publication and author proofing. The American Chemical
Society provides “Just Accepted” as a free service to the research community to expedite the
dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts
appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been
fully peer reviewed, but should not be considered the official version of record. They are accessible to all
readers and citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered
to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published
in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just
Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor
changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers
and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors
or consequences arising from the use of information contained in these “Just Accepted” manuscripts.
The Journal of Organic Chemistry is published by the American Chemical Society.
1155 Sixteenth Street N.W., Washington, DC 20036
Published by American Chemical Society. Copyright © American Chemical Society.
However, no copyright claim is made to original U.S. Government works, or works
produced by employees of any Commonwealth realm Crown government in the course
of their duties.

Page 1 of 16
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
Cu-NHC-TEMPO Catalyzed Aerobic Oxidation of Primary Alcohols
to Aldehydes
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Xiaolong Liu, † Qinqin Xia, † Yuejiao Zhang, † Congyan Chen, † and Wanzhi Chen*†‡
† Department of Chemistry, Zhejiang University, Xixi Campus, Hangzhou 310028, People’s Republic of
China. chenwzz@zju.edu.cn
‡ State Key Laboratory of Elemento-organic Chemistry, Nankai University, Tianjin 300071, People’s
Republic of China.
chenwzz@zju.edu.cn
RECEIVED DATE (to be automatically inserted after your manuscript is accepted if required
according to the journal that you are submitting your paper to)
SYNOPSIS TOC
ABSTRACT. Imidazolium salts bearing TEMPO groups react with commercially available copper
powder affording Cu-NHC complexes. The inꢀsitu generated Cu-NHC-TEMPO complexes are quite
efficient catalysts for aerobic oxidation of primary alcohols into aldehydes. The catalyst is easily
available, and various primary alcohols were selectively converted to aldehydes in excellent yields.
1
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 2 of 16
Introduction
1
2
3
4
5
6
7
8
9
The selective oxidation of alcohols is one of the most fundamental transformations in organic
synthesis since their corresponding carbonyl compounds play important roles in total synthesis of natural
products and fine chemicals.1 Classically, chromium and manganese oxides,2 Swern reagents,3 and
Dess-Martin reagents4 are often used. However, these stoichiometric oxidants feature serious drawbacks
such as employing stoichiometric heavy metal complexes, difficulties in handling hazardous wastes.
With ever-increasing environmental concerns, much attention has been devoted to the development of
catalytic aerobic alcohol oxidation methodologies.5 Accordingly, a remarkable number of transition
metal-catalyzed aerobic oxidation systems have been well-established including those using copper,6
palladium,7 and ruthenium catalysts.8 Of particular interest are the catalytic systems employing copper
salts in combination with TEMPO (2,2,6,6-tetramethyl-piperidyl-1-oxy),9 and various N ligands such as
Bpy (2,2’-bipyridine),9c,9h DABCO (1,4-diazabicyclo[2.2.2]octane),9g and TMDP (4,4’-trimethylene-
dipyridine)9f (Eq. A in Figure 1). However, additional base is often needed9c,9d,9h which limits their
application in the oxidation of the base-sensitive alcohols. Recently, a transition metal-free system for
aerobic oxidations catalyzed by TEMPO/NaNO2 has been developed.10 Among these results, TEMPO
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
-
-
functionalized imidazolium salts such as [Imim-TEMPO]+X- (X = Cl-, BF4 , and FeCl4 , Eq. B) have
attracted special attention due to their outstanding catalytic and structural properties.10c-e
As the potential alternatives to the traditional nitrogen and phosphine ligands, N-heterocyclic carbenes
(NHCs) have gained great interests due to their unique properties.11 The performance of NHCs is easily
tuned through introduction of various functional groups at N-positions.12 We have reported that many
transition metal complexes can be easily obtained from the direct reaction of metal powders and
imidazolium salts.13 We speculate that a TEMPO-anchored imidazolium salt combining copper powder
would generate a copper-NHC complex bearing TEMPO. Such a complex would be efficient for alcohol
oxidation since intramolecular proton abstraction is facile. In continuation of our interest in metal-NHC
chemistry of the first transition period,13a,13c,14 herein we present the inꢀsitu generated Cu-NHC-TEMPO
(Eq. C) catalyzed aerobic alcohol oxidation. The ligands precursors are easily available, and the present
2
ACS Paragon Plus Environment

Page 3 of 16
The Journal of Organic Chemistry
catalyst can be easily prepared from copper powder and showed excellent selectivity of aldehydes in
excellent yields under mild conditions in air.
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Scheme 1. Strategies towards TEMPO-involved aerobic alcohol oxidation
Results and discussion
Scheme 2. The Cu-NHC complexes and ligand precursors
The imidazolium salts (2a-2e) were prepared from N-substituted imidazole and 4-(2-haloacetoxy)-
TEMPO,15 and 2f was prepared following the same procedure by using N-mesitylimidazole and
cyclohexyl 2-bromoacetate (Scheme 2). Imidazolium salts 2a-2e were isolated as paramagnetic solids.
The paramagnetic compounds can be reduced to their corresponding TEMPOH derivatives, which were
13
characterized by 1H and C NMR spectroscopy. The imidazolium salts 2a-2f reacted with commercial
3
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 4 of 16
copper powder smoothly giving homogeneous light yellow solutions. We have not been able to obtain
single crystals avoiding fully characterization of the resulting copper-NHC complexes. Positive-ion ESI
analysis of the solutions from the imidazolium salts with quantitative amount of copper revealed the
formation of Cu-NHCs species. EPR spectra of 2b and its corresponding Cu-NHC-TEMPO complexes
were recorded at room temperature, and both pronounced peaks were observed at g = 2.007
characteristic of the nitroxyl radical (see Supporting Information). The in situ generated Cu-NHC
complexes were evaluated as catalysts for alcohol oxidation. The initial study was carried out using
decan-1-ol (1a) as the model substrate to optimize the reaction conditions, and the results were
summarized in Table 1. In CH3CN at 50 °C, all 2a-2d are active, and 2b is the most efficient one giving
decanal in 17% yield (entries 1-4). Blank experiments showed that either copper powder or 2b itself is
totally inefficient (entries 5 and 6). When oxidation of decan-1-ol was attempted using 2b and CuBr as
catalyst, only trace amount of 3a was obtained (entry 7). The influence of the solvents on the reaction is
also apparent (entries 8-12). The oxidation proceeded more efficiently in chlorobenzene than in other
solvents, giving a relative higher yield of 36%, and thus was chosen as the solvent for further
optimization (entry 9). The yield was significantly increased to 64% when the amount of the catalyst
was increased to 10 mol % (entry 13). The reaction was also tested under molecular oxygen, and no
significant improvement was observed (entry 14). Base has proved to favor the oxidation reaction of
alcohols in most reported Cu/N ligand/TEMPO systems.9c,9d,9h However, bases showed negative effect
for the present catalytic system. Addition of KOtBu or Et3N resulted in obvious decrease of yields to
21% and 19%, respectively (entries 15 and 16). In addition, when 2b was replaced by 2e, the yield of
decanal was sharply increased to 80%, indicating that the counter anion also play an important role in
oxidation (entry 17). Further increase of the temperature to 80 °C, up to 95 % of decanal could be
obtained (entry 18). Combination of 2f and copper powder showed no activity. For comparison, the
catalytic activities of [(IMes)CuCl], [(IMes)CuBr], and [(IPr)CuBr] complexes were also examined.
[(IMes)CuBr] and [(IPr)CuBr] themselfs are totally inactive. Unexpectedly, their combinations with
TEMPO only showed negligible activity with trace amount of decanal (3a) detected (entries 21 and 22).
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
4
ACS Paragon Plus Environment

Page 5 of 16
The Journal of Organic Chemistry
The copper-catalyzed alcohol oxidation often involves the use of N-ligands, and the catalytic activity of
Cu-NHC complexes was not yet explored. The results showed that simple combinations of commonly
used Cu-NHC complexes such as [(IPr)CuX] or [(IMes)CuX] and TEMPO do not show activities for
alphatic alcohol 1a. However, the catalytic activity of Cu-NHCs bearing a TEMPO was greatly
improved. The mechanism is still unclear, and it was tentatively proposed that Cu-NHC complex
anchored TEMPO is efficient for alcohol oxidation since intramolecular proton abstraction is facile.
Table 1. Optimization of Reaction Conditions a
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
additive
(mol %)
entry
cat. (mol %)
solvent
temp (°C)
yield (%)b
1
2
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
DMSO
C6H5Cl
Toluene
THF
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
12
17
2a + Cu (5)
2b + Cu (5)
2c + Cu (5)
2d + Cu (5)
2b (5)
3
9
4
14
5
NR
NR
trace
27
6
Cu (5)
7
2b + CuBr (5)
2b + Cu (5)
8
9
36
2b + Cu (5)
10
11
12
13
14
15
16
17
18
19
20
21
22
24
2b + Cu (5)
trace
trace
64
2b + Cu (5)
DMF
2b + Cu (5)
C6H5Cl
C6H5Cl
C6H5Cl
C6H5Cl
C6H5Cl
2b + Cu (10)
2b + Cu (10)
2b + Cu (10)
2b + Cu (10)
2e + Cu (10)
2e + Cu (10)
2f + Cu (10)
[(IMes)CuCl] (10)
[(IMes)CuBr] (5)
[(IPr)CuBr] (5)
67c
KOtBu (10)
Et3N (10)
21
19
80
C6H5Cl
C6H5Cl
C6H5Cl
CH3CN
CH3CN
80
80
80
50
50
95
NR
NR
TEMPO (5)
TEMPO (5)
trace
trace
5
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 6 of 16
a Reaction conditions: Imidazolium salt and copper powder were stirred at 70 °C for 5
h before addition of alcohol (1.0 mmol), and the stirring was continued for 15 h in
air. b GC yield. c O2.
1
2
3
4
5
6
7
8
9
To probe the efficiency of the inꢀsitu Cu-NHC-TEMPO catalytic system, the oxidation of other
aliphatic alcohols were examined under the optimized conditions as summarized in Table 2. Studies
commenced with the oxidation of straight-chain C7-C10 alcohols, and all these primary alcohols were
selectively oxidized to aldehydes in GC yields of 88%-95% (entries 1-4). Cyclohexylmethanol (1e)
could also be converted into its corresponding product in a slightly lower yield of 86% (entry 5). An
almost quantitative transformation was obtained when 3,7-dimethyloct-6-en-1-ol (1f) was applied, and
no over oxidation of the alkene was observed (entry 6). However, a C-C cleavage was observed for the
oxidation of 2-phenylethanol and 3-phenylpropan-1-ol under the same conditions giving benzaldehyde
as the major product in moderate yields (entries 7 and 8).
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Table 2. Aerobic oxidation of aliphatic primary alcohols a
2e (10 mol %)
Cu (10 mol %)
R
R
OH
O
C6H5Cl (3 mL)
80 oC, 15h, air
3
1
entry
1
alcohols
product
yield %b
95 (76)
1a
1b
1c
1d
3a
2
3
4
91
90
88
3b
3c
3d
5
6
86
1e
3e
99 (85)
3f
1f
6
ACS Paragon Plus Environment

Page 7 of 16
The Journal of Organic Chemistry
7
8
trace + 34
13 + 60
1
2
3
4
5
6
7
8
3g +
3h +
3i
3i
1g
1h
a
Reaction conditions: 2e (0.1 mmol, 10 mol %) and copper powder (0.1 mmol,
10 mol %) in clorobenzene (3 mL) were stirred at 70 °C for 5 h before addition
of alcohol (1.0 mmol), and the stirring was continued at 80 °C for 15 h. GC
b
9
yield.
10
11
12
13
14
15
16
The aerobic oxidation of various benzylic, allylic, propargylic, and heterocyclic-substituted alcohols
was also investigated (Table 3). As have been reported, benzylic alcohols usually show higher
reactivities than aliphatic alcohols.9 Hence, phenylmethanol (1i) was first tested with a catalyst loading
of 1 mol %, and the reaction afforded benzaldehyde in 75% yield within 15 hours at 80 ºC (Table 3,
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
entry 1). When the amount of the catalyst was doubled, the oxidation of phenylmethanol was completed
within 5 hours in 96 % yield (entry 1). At the catalyst loading of 2 mol %, both benzylic alcohols with
either electron-donating or electron-withdrawing substituents can be oxidized into their corresponding
aldehydes in excellent yields (entries 2-10). However, the oxidation of (4-nitrophenyl)methanol (1q) and
(2-nitrophenyl)methanol (1r) have to elongated to 20 h to reach completion(entries 9 and 10).
Anthracen-9-ylmethanol (1t) is much more inert than naphthalen-1-ylmethanol (1s), and anthracene-10-
carbaldehyde (3t) was obtained in only 49 % yield at a catalyst loading of 2 mol % probably due to the
steric effect (entries 11 and 12). When the catalyst loading was increased to 5 %, 3t could be isolated in
94 % yield (entry 12). Under the same conditions, 3-phenylprop-2-yn-1-ol (1u) and 3-phenylprop-2-en-
1-ol (1v) could be also almost quantitatively transformed into their corresponding aldehydes, and no
over oxidation products were observed (entry 13). The heteroaryl alcohols such as furan-2-ylmethanol
(1w) and thiophen-2-ylmethanol (1x) were smoothly transformed into their aldehyde products in 71%
and 73% yields, respectively (entries 15 and 16). However, no oxidation was observed with pyridin-2-
ylmethanol (1y).
Table 3. Aerobic oxidation of substituted benzylic and other active alcohols a
7
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 8 of 16
1
2
3
4
5
6
7
8
9
entry
1
alcohol
product
yield %
75b,c
96b
1i
3i
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
2
3
84
94
1j
3j
1k
3k
OH
4
5
95
81
N
1l
3l
1m
1n
1o
3m
3n
6
7
8
85
92
94
CHO
Br
3o
1p
3p
9
98d
97d
1q
3q
10
1r
3r
11.
99
3s
1s
49
12
13
94e
3t
1t
24
94e
1u
3u
8
ACS Paragon Plus Environment

Page 9 of 16
The Journal of Organic Chemistry
95e
71
1
2
3
4
5
6
7
8
14
15
3v
1v
3w
3x
3y
1w
16
17
73
-
9
1x
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
1y
a
Reaction conditions: 2e (0.02 mmol, 2 mol %) and copper powder (0.02
mmol, 2 mol %) in clorobenzene (3 mL) were stirred at 70 °C for 5 h
before addition of alcohol (1.0 mmol), and the stirring was continued at 80
°C for 15 h. b GC yield. c 2e 0.01 mmol (1 mol %) and copper powder 0.01
mmol (1 mol %) were used. 20 h. 2e 0.05 mmol (5 mol %) and copper
powder 0.05 mmol (5 mol %) were used.
d
e
Conclusion
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
In summary, inꢀsitu generated Cu-NHC-TEMPO catalyzed aerobic oxidation of primary alcohols into
aldehydes is presented. The catalytic system was applicable to various primary alcohols, and their
aldehydes were selectively obtained in excellent yields. At present, it was unclear of the structural
changes of the catalyst in the catalytic cycle. The isolation of the catalyst after completion of oxidation
was hard to proceed due to its low catalyst loading and good solubility in chlorobenzene. To fully
understand the catalytic performance, further work will be done.
Experimental Section
All the chemicals were obtained from commercial suppliers and used without further purification.
[(IMes)CuCl],16 [(IMes)CuBr],16 [(IPr)CuBr],16 2-haloacetoxy-substituted complexes,15a,17 and carbene
precursor 2a15a were prepared according to the known procedure. The paramagnetic 2b-2e were
characterized by elemental analyses and further identified by 1H and 13C spectroscopy after reduction to
their corresponding TEMPOH derivatives using phenlyhydrazine as the reductant.15a
Synthesis of imidazolium salt 2b
9
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 10 of 16
A solution of N-mesitylimidazole (1.86 g, 10 mmol) and 4-(2-chloroacetoxy)-TEMPO (2.98 g, 12
mmol) in 30 mL of CH3CN was refluxed for 12 h. The solution was then concentrated to ca. 5 mL.
Addition of ethyl acetate (20 mL) to the resulting solution afforded an orange yellow precipitate which
was collected and washed with ethyl acetate (10 ml × 3). Yield: 4.05 g, 93%. Anal. Calcd for
1
2
3
4
5
6
7
8
9
1
C23H33ClN3O3: C, 63.51; H, 7.65; N, 9.66. Found: C, 63.18; H, 7.87; N, 9.62. The hydroxyl form: H
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
NMR (400 MHz, D2O): δ 7.73 (s, 1H), 7.59 (s, 1H), 7.12 (s, 2H), 5.27-5.25 (m, 3H), 2.30 (s, 3H), 2.15-
13
2.12 (m, 2H), 2.01 (s, 6H), 1.72 (t, J = 11.2 Hz, 2H), 1.27 (s, 6H), 1.25 (s, 6H). C NMR (100 MHz,
D2O): δ 166.8, 141.4, 137.9, 134.4, 130.4, 129.0, 124.0, 123.8, 68.6, 65.9, 63.0, 50.2, 41.2, 28.6, 20.0,
16.1.
Synthesis of imidazolium salt 2c
Complex 2c was obtained as a light yellow solid following the same procedure as for 2b by using N-
2,6-diisopropylphenylimidazole (2.28 g, 10 mmol) and 4-(2-chloroacetoxy)-TEMPO (2.98 g, 12 mmol).
Yield: 4.15 g, 87%. Anal. Calcd for C26H39ClN3O3: C, 65.46; H, 8.24; N, 8.81. Found: C, 65.73; H,
1
8.19; N, 8.77. The hydroxyl form: H NMR (400 MHz, D2O): δ 7.75 (s, 1H), 7.72 (s, 1H), 7.59 (t, J =
7.8 Hz, 1H), 7.42 (d, J = 8.0 Hz, 2H), 5.25-5.22 (m, 3H), 2.35-2.28 (m, 2H), 2.06-2.03 (m, 2H), 1.62 (t,
13
J = 12.0 Hz, 2H), 1.19 (s, 6H), 1.17 (s, 6H), 1.11 (s, 12H). C NMR (100 MHz, D2O): δ 166.8, 145.4,
131.7, 129.8, 125.0, 124.3, 124.2, 124.0, 69.6, 60.6, 50.2, 41.9, 29.5, 28.1, 23.1, 22.9.
Synthesis of imidazolium salt 2d
Complex 2d was obtained as a yellow solid following the same procedure as for 2b by using 2-
(imidazolyl)pyridine (1.45 g, 10 mmol) and 4-(2-chloroacetoxy)-TEMPO (2.98 g, 12 mmol). Yield: 2.98
g, 76%. Anal. Calcd for C19H26ClN4O3: C, 57.94; H, 6.65; N, 14.22. Found: C, 57.67; H, 6.82; N, 14.13.
The hydroxyl form: 1H NMR (400 MHz, DMSO-d6): δ 10.06 (s, 1H), 8.66 (s, 1H), 8.57 (s, 1H), 8.23 (s,
1H), 8.06-8.00 (m, 2H), 7.67 (s,1H), 7.42 (s, 1H), 5.32 (s, 2H), 5.13-5.08 (m, 1H), 1.98-1.92 (m, 2H),
13
1.56-1.51 (m, 2H), 1.10 (s, 6H), 1.09 (s, 6H). C NMR (100 MHz, DMSO-d6): δ 166.1, 149.4, 146.2,
140.8, 136.2, 125.5, 125.0, 119.0, 114.3, 69.1, 58.2, 50.2, 43.3, 32.0, 20.4.
Synthesis of imidazolium salt 2e
10
ACS Paragon Plus Environment

Page 11 of 16
The Journal of Organic Chemistry
Complex 2e was obtained as a yellow solid following the same procedure as for 2b by using N-
mesitylimidazole (1.86 g, 10 mmol) and 4-(2-bromoacetoxy)-TEMPO (3.52 g, 12 mmol). Yield: 4.25 g,
89%. Anal. Calcd for C23H33BrN3O3: C, 57.62; H, 6.94; N, 8.76. Found: C, 57.57; H, 7.02; N, 8.56. The
hydroxyl form: 1H NMR (400 MHz, D2O): δ 7.74 (s, 1H), 7.57 (s, 1H), 7.11 (s, 2H), 5.27-5.25 (m, 3H),
1
2
3
4
5
6
7
8
9
13
2.29 (s, 3H), 2.17-2.14 (m, 2H), 2.01 (s, 6H), 1.74 (t, J = 11.6 Hz, 2H), 1.27 (s, 3H), 1.26 (s, 3H). C
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
NMR (100 MHz, D2O): δ 166.8, 141.4, 137.6, 134.4, 130.4, 129.1, 124.0, 123.8, 68.7, 65.9, 63.0, 50.2,
41.3, 28.6, 20.0, 16.2.
Synthesis of imidazolium salt 2f
A solution of N-mesitylimidazole (1.86 g, 10 mmol) and cyclohexyl 2-bromoacetate (2.65 g, 12
mmol) in 30 mL of toluene was refluxed for 12 h. The resulting white solid was filtered and washed
with Et2O (10 ml × 3). Yield: 3.50 g, 86%. Anal. Calcd for C20H27BrN2O2: C, 58.97; H, 6.68; N, 6.88.
Found: C, 58.74; H, 6.55; N, 7.02. 1H NMR (400 MHz, DMSO-d6): δ 9.58 (s, 1H), 8.13 (s, 1H), 8.00 (s,
1H), 7.16 (s, 2H), 5.42 (s, 2H), 4.85-4.81 (m, 1H), 2.33 (s, 3H), 2.03 (s, 6H), 1.81 (br, 2H), 1.63 (br,
13
2H), 1.46-1.24 (m, 6H). C NMR (100 MHz, DMSO-d6): δ 165.9, 140.3, 138.9, 134.2, 131.1, 129.3,
124.5, 123.4, 74.3, 50.1, 30.8, 24.7, 22.8, 20.6, 16.8.
General procedure for the synthesis of products 3
For aliphatic primary alcohols: In a glass tube, a mixture of 2e (48 mg, 0.1 mmol) and copper powder
(6.5 mg, 0.1 mmol) in 3.0 ml of chlorobenzene was stirred 70 °C for 5 h under air. Then alcohol (1.0
mmol) was added and the stirring was continued at 80 °C for 15 h. After completion of the oxidation,
the resulting solution was cooled to room temperature. The reaction mixture was concentrated under
reduced pressure. The residue was purified by flash column chromatography on silica gel (ethyl
acetate/petroleum ether) to afford the aldehyde products. For substituted benzylic and other active
alcohols, 2 mol% of 2e and copper powder were used following the same procedure described above
unless otherwise stated.
11
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 12 of 16
Decanal (3a).9b Colorless oil; yield: 119 mg, 76%; H NMR (400 MHz, CDCl3): δ 9.73 (s, 1H), 2.39
1
1
2
3
13
(t, J = 7.4 Hz, 2H), 1.61-1.57 (m, 2H), 1.26-1.23 (m, 12H), 0.84 (t, J = 6.6 Hz, 3H). C NMR (100
4
5
6
MHz, CDCl3): δ 203.0, 44.0, 31.9, 29.5, 29.4, 29.3, 29.2, 22.7, 22.2, 14.2.
3,7-dimethyloct-6-enal (3f).9b Colorless oil; yield: 131 mg, 85%; 1H NMR (400 MHz, CDCl3): δ 9.72
(m, 1H), 5.06 (t, J = 6.8 Hz, 1H), 2.41-2.35 (m, 1H), 2.23-2.17 (m, 1H), 2.07-1.94 (m, 3H), 1.65 (s, 3H),
1.57 (s, 3H), 1.35-1.23 (m, 2H), 0.94 (d, J = 6.4 Hz, 3H). 13C NMR (100 MHz, CDCl3): δ 203.1, 131.8,
124.1, 51.1, 37.0, 27.8, 25.8, 25.5, 19.9, 17.7.
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
4-methylbenzaldehyde (3j).9e Colorless oil; yield: 101 mg, 84%; 1H NMR (400 MHz, CDCl3): δ 9.94
(s, 1H), 7.76 (d, J = 7.6 Hz, 2H), 7.31 (d, J = 8.4 Hz, 2H), 2.42 (s, 3H). 13C NMR (100 MHz, CDCl3): δ
192.2, 145.7, 134.2, 129.9, 129.8, 22.0.
1
4-methoxybenzaldehyde (3k).9e Colorless oil; yield: 128 mg, 94%; H NMR (400 MHz, CDCl3): δ
9.85 (s, 1H), 7.81 (d, J = 8.8 Hz, 2H), 6.98 (d, J = 8.4 Hz, 2H), 3.86 (s, 3H). 13C NMR (100 MHz,
CDCl3): δ 191.0, 164.6, 132.1, 129.9, 114.3, 55.6.
1
4-(dimethylamino)benzaldehyde (3l).6d Light yellow solid; yield: 142 mg, 95%; H NMR (400
MHz, CDCl3): δ 9.72 (s, 1H), 7.72 (d, J = 8.8 Hz, 2H), 6.68 (d, J = 8.8 Hz, 2H), 3.06 (s, 6H). 13C NMR
(100 MHz, CDCl3): δ 190.4, 154.4, 132.0, 125.1, 111.1, 40.1.
1
3,4-dimethoxybenzaldehyde (3m).9e White solid; yield: 134 mg, 81%; H NMR (400 MHz, CDCl3):
δ 9.79 (s, 1H), 7.40 (d, J = 8.0 Hz, 1H), 7.34 (s, 1H), 6.92 (d, J = 8.4 Hz, 1H), 3.91 (s, 3H), 3.88 (s, 3H).
13C NMR (100 MHz, CDCl3): δ 190.9, 154.4, 149.5, 130.1, 126.9, 110.3, 108.8, 56.2, 55.9.
1
4-chlorobenzaldehyde (3n).18 White solid; yield: 119 mg, 85%; H NMR (400 MHz, CDCl3): δ 9.97
(s, 1H), 7.81 (d, J = 8.4 Hz, 2H), 7.50 (d, J = 8.4 Hz, 2H). 13C NMR (100 MHz, CDCl3): δ 191.1, 141.0,
134.8, 131.0, 129.6.
1
4-bromobenzaldehyde (3o).9e White solid; yield: 170 mg, 92%; H NMR (400 MHz, CDCl3): δ 9.95
(s, 1H), 7.75-7.72 (m, 2H), 7.68-7.66 (m, 2H). 13C NMR (100 MHz, CDCl3): δ 191.2, 135.1, 132.5,
131.1, 129.9.
12
ACS Paragon Plus Environment

Page 13 of 16
The Journal of Organic Chemistry
2-bromobenzaldehyde (3p).9b Colorless oil; yield: 174 mg, 94%; H NMR (400 MHz, CDCl3): δ
10.35 (s, 1H), 7.91-7.89 (m, 1H), 7.64 (d, J = 7.2 Hz, 1H), 7.47-7.40 (m, 2H). 13C NMR (100 MHz,
CDCl3): δ 192.1, 135.5, 134.0, 133.5, 130.0, 128.0, 127.3.
1
1
2
3
4
5
6
4-nitrobenzaldehyde (3q).9e Yellow solid; yield: 148 mg, 98%; 1H NMR (400 MHz, CDCl3): δ 10.15
(s, 1H), 8.38 (d, J = 8.8 Hz, 2H), 8.07 (d, J = 8.0 Hz, 2H). 13C NMR (100 MHz, CDCl3): δ 190.4, 151.3,
140.2, 130.6, 124.4.
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1
2-nitrobenzaldehyde (3r).10e Yellow solid; yield: 146 mg, 97%; H NMR (400 MHz, CDCl3): δ
13
10.36 (s, 1H), 8.09 (d, J = 8.0 Hz, 1H), 7.92-7.90 (m, 1H), 7.81-7.74 (m, 2H). C NMR (100 MHz,
CDCl3): δ 188.3, 149.5, 134.2, 133.8, 131.3, 129.7, 124.6.
1
1-naphthaldehyde (3s). 6d Light yellow oil; yield: 154 mg, 99%; H NMR (400 MHz, CDCl3): δ
10.34 (s, 1H), 9.25 (d, J = 8.4 Hz, 1H), 8.03 (d, J = 8.4 Hz, 1H), 7.91-7.86 (m, 2H), 7.67 (t, J = 7.6 Hz,
1H), 7.58-7.54 (m, 2H). 13C NMR (100 MHz, CDCl3): δ 193.6, 136.8, 135.3, 133.6, 131.2, 130.4, 129.0,
128.4, 126.9, 124.8.
1
anthracene-9-carbaldehyde (3t).18 Yellow solid; yield: 194 mg, 94%; H NMR (400 MHz, CDCl3):
δ 11.52 (s, 1H), 8.98 (d, J = 9.2 Hz, 2H), 8.69 (s, 1H), 8.06 (d, J = 8.4 Hz, 2H), 7.69 (t, J = 7.6 Hz, 2H),
7.55 (t, J = 7.2 Hz, 2H). 13C NMR (100 MHz, CDCl3): δ 193.2, 135.5, 132.3, 131.2, 129.4, 129.3, 125.8,
124.7, 123.6.
3-phenylpropiolaldehyde (3u).9h Light yellow oil; yield: 122 mg, 94%; 1H NMR (400 MHz, CDCl3):
δ 9.40 (s, 1H), 7.59 (d, J = 7.2 Hz, 2H), 7.48 (t, J = 7.4 Hz, 1H), 7.39 (t, J = 7.6 Hz, 2H). 13C NMR (100
MHz, CDCl3): δ 176.9,133.3, 131.3, 128.7, 119.3, 95.1, 88.4.
1
cinnamaldehyde (3v).9e Colorless oil; yield: 125 mg, 95%; H NMR (400 MHz, CDCl3): δ 9.68 (d, J
13
= 7.6 Hz, 1H), 7.55-7.53 (m, 2H), 7.47-7.41 (m, 4H), 6.72-6.66 (m, 1H). C NMR (100 MHz, CDCl3):
δ 193.8, 152.9, 133.9, 131.3, 129.1, 128.7, 128.5.
1
furan-2-carbaldehyde (3w).9h Light yellow oil; yield: 68 mg, 71%; H NMR (400 MHz, CDCl3): δ
9.55 (s, 1H), 7.61 (s, 1H), 7.17 (d, J = 3.6 Hz, 1H), 6.51 (d, J = 2.0 Hz, 1H). 13C NMR (100 MHz,
CDCl3): δ 177.7, 152.9, 148.0, 121.1, 112.5.
13
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 14 of 16
thiophene-2-carbaldehyde (3x).9h Light yellow oil; yield: 82 mg, 73%; 1H NMR (400 MHz, CDCl3):
δ 9.90 (s, 1H), 7.77-7.72 (m, 2H), 7.18 (t, J = 4.4 Hz, 1H). 13C NMR (100 MHz, CDCl3): δ 183.1, 143.9,
136.5, 135.2, 128.4.
1
2
3
4
5
6
7
8
9
ACKNOWLEDGMENT. The project is supported by Natural Science Foundation of China (No.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
21072170 and J1210042).
Supporting Information Available. Copies of H and 13C NMR spectra for 2b-2f and 3a-3x, ESI
1
analysis of the in situ generated Cu-NHC species, and EPR spectra of 2b and its corresponding Cu-
NHC-TEMPO species. This material is available free of charge via the Internet at http://pubs.acs.org.
References
(1)
(a) Sheldon, R. A.; Kochi. J. K. MetalꢀCatalysed Oxidations of Organic Compounds. Academic
Press, New York, 1981. (b) Hudlicky, M. Oxidations in Organic Chemistry; American Chemical
Society: Washington, DC, 1990.
(2)
Foot, J.; Raw, S. A. Acc. Chem. Res. 2005, 38, 851.
(3) (a) Mancuso, A. J.; Huang, S. L.; Swern, D. J. Org. Chem. 1978, 43, 2480. (b) Mancuso, A. J.;
Brownfain, D. S.; Swern, D. J. Org. Chem. 1979, 44, 4148.
(4) (a) Dess, D. B.; Martin, J. C. J. Org. Chem. 1983, 48, 4155. (b) Jiang, Y.; Chen, W.; Lu, W.
Tetrahedron 2013, 69, 3669.
(a) Corey, E. J.; Suggs, J. W. Tetrahedron Lett. 1975, 16, 2647. (b) Taylor, R. J. K.; Reid, M.;
(5)
(a) Sheldon, R. A.; Arends, I. W. C. E.; ten Brink, G. J.; Dijksman, A. A. Acc. Chem. Res. 2002,
35, 774. (b) Zhan, B. Z.; Thompson, A. Tetrahedron 2004, 60, 2917.
(6)
(a) Chaudhuri, P.; Hess, M.; Flörke, U.; Wieghardt, K. Angew. Chem., Int. Edit. 1998, 37, 2217.
(b) Markó, I. E.; Gautier, A.; Dumeunier, R. L.; Doda, K.; Philippart, F.; Brown, S. M.; Urch, C. J.
Angew. Chem., Int. Edit. 2004, 43, 1588. (c) Gartshore, C. J.; Lupton, D. W. Adv. Synth. Catal. 2010,
352, 3321. (d) Zhu, Y.; Zhao, B.; Shi, Y. Org. Lett. 2013, 15, 992.
14
ACS Paragon Plus Environment

Page 15 of 16
The Journal of Organic Chemistry
(7)
(a) ten Brink, G. J.; Arends, I. W. C. E.; Sheldon, R. A. Science 2000, 287, 1636. (b) Mori, K.;
1
2
3
4
5
Hara, T.; Mizugaki, T.; Ebitani, K.; Kaneda, K. J. Am. Chem. Soc. 2004, 126, 10657. (c) Mueller, J. A.;
Goller, C. P.; Sigman, M. S. J. Am. Chem. Soc. 2004, 126, 9724.
6
7
8
(8)
(a) Dijksman, A.; Marino-González, A.; Payeras, A. M. I.; Arends, I. W. C. E.; Sheldon, R. A. J
9
Am Chem Soc 2001, 123, 6826. (b) Zhan, B. Z.; White, M. A.; Sham, T. K.; Pincock, J. A.; Doucet, R.
J.; Rao, K. V. R.; Robertson, K. N.; Cameron, T. S. J. Am. Chem. Soc. 2003, 125, 2195.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(9)
(a) Semmelhack, M. F.; Schmid, C. R.; Cortés, D. A.; Chou, C. S. J. Am. Chem. Soc. 1984, 106,
3374. (b) Ragagnin, G.; Betzemeier, B.; Quici, S.; Knochel, P. Tetrahedron 2002, 58, 3985. (c) Gamez,
P.; Arends, I. W. C. E.; Reedijk, J.; Sheldon, R. A. Chem. Commun. 2003, 2414. (d) Gamez, P.; Arends,
I. W. C. E.; Sheldon, R. A.; Reedijk, J. Adv. Synth. Catal. 2004, 346, 805. (e) Jiang, N.; Ragauskas, A. J.
Org. Lett. 2005, 7, 3689. (f) Jiang, N.; Ragauskas, A. J. J. Org. Chem. 2006, 71, 7087. (g) Mannam, S.;
Alamsetti, S. K.; Sekar, G. Adv. Synth. Catal. 2007, 349, 2253. (h) Hoover, J. M.; Stahl, S. S. J. Am.
Chem. Soc. 2011, 133, 16901.
(10) (a) Liu, R.; Liang, X.; Dong, C.; Hu, X. J. Am. Chem. Soc. 2004, 126, 4112. (b) Wang, X.; Liu,
R.; Jin, Y.; Liang, X. Chem. Eur. J. 2008, 14, 2679. (c) Miao, C. X.; He, L. N.; Wang, J. Q.; Wang, J. L.
Adv. Synth. Catal. 2009, 351, 2209. (d) Miao, C. X.; He, L. N.; Wang, J. L.; Wu, F. J. Org. Chem. 2010,
75, 257. (e) Miao, C. X.; Wang, J. Q.; Yu, B.; Cheng, W. G.; Sun, J. A.; Chanfreau, S.; He, L. N.; Zhang,
S. J. Chem. Commun. 2011, 47, 2697.
(11) (a) Díez-González, S.; Marion, N.; Nolan, S. P. Chem. Rev. 2009, 109, 3612. (b) Vougioukalakis,
G. C.; Grubbs, R. H. Chem. Rev. 2010, 110, 1746. (c) Fortman, G. C.; Nolan, S. P. Chem. Soc. Rev.
2011, 40, 5151.
(12) (a) Lin, J. C. Y.; Huang, R. T. W.; Lee, C. S.; Bhattacharyya, A.; Hwang, W. S.; Lin, I. J. B.
Chem. Rev. 2009, 109, 3561. (b) Poyatos, M.; Mata, J. A.; Peris, E. Chem. Rev. 2009, 109, 3677. (c)
Schuster, O.; Yang, L.; Raubenheimer, H. G.; Albrecht, M. Chem. Rev. 2009, 109, 3445.
15
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 16 of 16
(13) (a) Liu, B.; Xia, Q.; Chen, W. Angew. Chem., Int. Edit. 2009, 48, 5513. (b) Liu, B.; Liu, X.;
Chen, C.; Chen, C.; Chen, W. Organometallics 2012, 31, 282. (c) Liu, X.; Pan, S.; Wu, J.; Wang, Y.;
Chen, W. Organometallics 2013, 32, 209.
1
2
3
4
5
6
7
8
9
(14) Liu, B.; Zhang, Y.; Xu, D.; Chen, W. Chem. Commun. 2011, 47, 2883.
(15) (a) Wu, X.; Ma, L.; Ding, M. X.; Gao, L. X. Synlett. 2005, 607. (b) Qian, W.; Jin, E.; Bo, W.;
Zhang, Y. Tetrahedron 2006, 62, 556.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(16) Díez-González, S.; Escudero-Adán, E. C.; Benet-Buchholz, J.; Stevens, E. D.; Slawin, A. M. Z.;
Nolan, S. P. Dalton Trans. 2010, 39, 7595.
(17) Araki, K.; Nakamura, R.; Otsuka, H.; Shinkai, S. J. Chem. Soc., Chem. Comm. 1995, 2121.
(18) Rout, L.; Nath, P.; Punniyamurthy, T. Adv. Synth. Catal. 2007, 349, 846.
16
ACS Paragon Plus Environment