Copper-catalyzed methyl esterification reactions via C-C bond cleavage

Article abstract of DOI:10.1021/jo4016387

The highly effective synthesis of methyl esters from benzylic alcohols, aldehydes, or acids via copper-catalyzed C-C cleavage from tert-butyl hydroperoxide is reported in this paper for the first time. Our protocol is easily accessible and practical, making it a possible supplement for the traditional way.

Full text of DOI:10.1021/jo4016387

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Article
Copper-Catalyzed Methyl Esterification Reactions via C-C Bond Cleavage
Yan Zhu, Hong Yan, Linhua Lu, Defu Liu, Guangwei Rong, and Jincheng Mao
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/jo4016387 • Publication Date (Web): 02 Sep 2013
Downloaded from http://pubs.acs.org on September 3, 2013
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Copper-Catalyzed Methyl Esterification Reactions via C-C Bond Cleavage
Yan Zhu, Hong Yan, Linhua Lu, Defu Liu, Guangwei Rong, and Jincheng Mao*
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Key Laboratory of Organic Synthesis of Jiangsu Province, College of Chemistry, Chemical Engineering and Materials Science,
Soochow University, Suzhou 215123, P. R. China.
jcmao@suda.edu.cn
RECEIVED DATE (will be automatically inserted after manuscript is accepted).
O
N
O
O
Cu2+
O
2
OH
H
OH
R
R
R
OMe
R
,
O
OH
5
2 examples
TBAI, DMSO
up to 99% yield
Highly effective synthesis of methyl esters from benzylic alcohols, aldehydes or acids was reported in this paper for the first
time via copperꢀcatalyzed CꢀC cleavage from tertꢀbutyl hydroperoxide. Our protocol was easily accessible and practical,
which will be the possible supplement for the traditional way.
Introduction
O
O
OMe
O
N
O
O
N
S
O
O
O
O
N
F
S
OMe
O
O
OMe
Cl
O
MeO
Methyl jasmonate (A)
Fluthiacetꢀmethyl (B)
Biphenyldicarboxylate (C)
FIGURE 1. Representative organic compounds containing methyl ester moieties
As we know that the ester is one of the most important functional groups in chemicals. Among various types of esters, methyl
1
one is frequently appeared as building blocks in various natural products and polymers. It is noteworthy that many methyl esters
2
3
have biological activities (selected examples are shown in Figure 1). For example, methyl jasmonate (A) is a plant stress hormone,
4
exhibiting antiꢀcancer activity on human cancer cells; Fluthiacetꢀmethyl (B) is a postꢀemergence herbicide mainly for control of
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certain annual broadleaf weeds in corn and soybeans; Biphenyldicarboxylate (C) , as a traditional Chinese medicine, exhibits
antihapetotoxic (liver injury), anticonvulsive (cerebral protection), antitumor, antiHIV and antifungal activities.
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Thus, substantial attention has been paid on the approaches to acquire the methyl esters during the past several decades.
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Traditionally, methyl esters are prepared by the reaction of activated acid derivatives with methanol, which is a multiꢀstep process.
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Considering that benzylic alcohols are readily available, environmental friendly and simple to handle, they are usually employed as
0
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the substrates to synthesize methyl esters from methanol in many protocols. Recently, Beller and Lei independently reported some
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synthetically interesting Pdꢀcatalyzed oxidative crossꢀesterification of benzylic and aliphatic alcohols with methanol. In addition,
other transition metals such as Au, Ru, Ir and Zn also showed high efficiency for the crossꢀesterification reaction of benzylic
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alcohols (Scheme 1). In view of the sustainable development in the future, the lowꢀcost efficient metal catalysts need further
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investigation. With our ongoing interest in various crossꢀcoupling reactions, we describe our efforts on the copperꢀcatalyzed
methyl esterification reactions with peroxides, serving as both the oxidant and the source of methyl group (Scheme 1). To the best
of our knowledge, there is few example of copperꢀcatalyzed direct esterification of benzylic alcohols in the absence of methanol till
now. Furthermore, during the reaction, it was interesting to find that the cleavage of CꢀC bonds occurred simultaneously. Actually,
transition metalsꢀcatalyzed cleavage of C–C bonds as a versatile tool in modern organic synthesis has attracted much attention and
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emerged as a tremendous challenge during the past several years. More recently, Li and coꢀworkers reported a palladiumꢀ
1
2
catalyzed methylation of aryl CꢀH bonds. On the basis of our findings, we wish to develop a methodology of copperꢀcatalyzed Cꢀ
C bond cleavage followed by methyl esterification of benzylic alcohols.
O
Me
Cu
Pd, Au, Ru, Ir, Zn
OH
OH
O
R
R
R
[O]
OH
MeOH
O
Reported Work
Our Work
SCHEME 1. Strategies toward methyl esterification of benzylic alcohols
Result and discussion
Firstly, we began our investigation by examining the coupling of benzylic alcohol (1a) and TBHP in the presence of lowꢀcost
copper catalysis (Table 1, entry 1). However, no desired product was acquired. While TBAI (tetrabutylammonium iodide) was
added into the system as the additive, no reaction was observed (Table 1, entry 2). It is speculated that benzylic alcohol could not
1
3
be oxidized in the current system. Subsequently, base was employed to assist the oxidation of benzylic alcohol, and KOH could
afford 27% yield of methyl 4ꢀmethoxybenzoate (Table 1, entry 3). Further optimization showed that the corresponding ester could
be obtained in 79% yield when K PO was used as base (Table 1, entries 4ꢀ7). In addition, various copper sources were screened
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4
into the reaction (Table 1, entries 8ꢀ10) and copper quinolate was the best. Interestingly, no reaction occurred when tertꢀbutyl
peroxide and dicumyl peroxide were used (Table 1, entries 11ꢀ12). Investigation of the solvents (Table 1, entries 13ꢀ14) showed
that other solvents except DMSO, could hardly afford the ester. To our surprise, a yield of 92% of the desired product (2a) was
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acquired when higher amount of the oxidant was used (Table 1, entry 15). Under the same conditions, the control experiment
showed that the yield would be greatly reduced in the absence of catalyst or TBAI (Table 1, entries 16ꢀ17). It can be seen that TBAI
shows a key acceleration role in the methyl esterification. Actually, we have also tried some other metals, including Fe, Ni, Co and
et al. However, their catalytic effects were very poor.
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7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
a
TABLE 1. Optimization of reaction conditions for the methyl esterification of benzylic alcohol
O
Copper Cat. (20 mol%)
OH
Oxidant, base
OMe
OH
+
O
MeO
Additive, DMSO, air
MeO
1a
2a
b
Entry
Cu Cat.
Oxidant
Additive
Base
–
Yield (%)
NR
NR
27
1
2
3
4
5
6
7
8
9
Copper quinolate
Copper quinolate
Copper quinolate
Copper quinolate
Copper quinolate
Copper quinolate
Copper quinolate
Copper powder
CuI
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
DTBP
DCP
–
TBAI
TBAI
TBAI
TBAI
TBAI
TBAI
TBAI
TBAI
TBAI
TBAI
TBAI
TBAI
TBAI
TBAI
TBAI
–
–
KOH
EtONa
67
t
BuOK
47
K CO
72
2
3
4
4
4
4
4
4
4
4
4
4
4
K PO
79
3
K PO
73
3
K PO
31
3
1
1
1
0
1
2
Cu(OAc) .H O
K PO
75
2
2
3
Copper quinolate
Copper quinolate
Copper quinolate
Copper quinolate
Copper quinolate
–
K PO
NR
NR
NR
<5
3
K PO
3
c
13
TBHP
TBHP
TBHP
TBHP
TBHP
K PO
3
d,e
d
1
4
K PO
3
1
5
K PO
92
3
d
d
1
1
6
7
K PO
42
3
Copper quinolate
K PO
69
3
a
Reaction conditions: methoxybenzylic alcohol (0.3mmol), catalyst (0.06 mmol), oxidant (1.8 mmol), additive (0.12mmol, 40
o
b
c
mol%), base (0.6 mmol, 2 equiv), solvent (2 mL), 120 C, air, 24h. The yield based on methoxybenzylic alcohol. DMF as the
d
e
solvent. TBHP (2.4 mmol). Toluene as the solvent.
Under the optimized reaction conditions, various benzylic alcohol derivatives were examined and related results were
summarized in Table 2. It was shown that benzylic alcohols with electronꢀwithdrawing or electronꢀdonating groups were all well
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1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
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tolerated and the corresponding esters were obtained in moderate to excellent yields. The desired esters (2) were isolated in 70ꢀ92%
yields when benzylic alcohols with the electronꢀdonating methoxyl group were used (Table 2, entries 1ꢀ4). For the methyl,
isopropyl, and phenoxy groups, the desired esters (2e-2g) were acquired with 74%, 61% and 67% yields, respectively (Table 2,
entries 5ꢀ7). It was noteworthy that electronꢀwithdrawing nitryl group gave moderate yield of the corresponding ester (2h) (Table 2,
entry 8).
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
a
TABLE 2. Copper-catalyzed methyl esterification of various benzylic alcohols
O
Copper quinolate (20 mol%)
OH
OMe
R
R
TBHP (2.4 mmol), TBAI (0.12 mmol)
o
K PO (0.6 mmol), DMSO, 120 C, air, 24 h
3
4
1
2
b
Entry
1
Benzylic Alcohol
Product
Yield (%)
92
O
OH
OMe
OMe
OMe
2a
MeO
MeO
OMe
OH
OMe O
2
3
2b
2c
76
80
MeO
MeO
MeO
O
MeO
OH
OMe
OMe
O
MeO
OH
MeO
MeO
OMe
OMe
4
5
6
2d
2e
2f
70
74
61
MeO
OMe
OMe
O
OH
Me
Me
O
OH
OMe
O
O
OH
O
7
8
OMe
2g
2h
67
53
O
OH
OMe
2
O N
O N
2
a
Reaction conditions: benzylic alcohol (0.3 mmol), copper quinolate (0.06 mmol), TBHP (2.4 mmol, 70% aqueous solution), TBAI
o
b
(
0.12 mmol), K PO (0.6 mmol), DMSO (2 mL), 120 C, air, 24 h. The yield based on benzylic alcohol.
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During the methyl esterification of benzylic alcohols, corresponding acid was detected as the byꢀproduct in the crude reaction
mixture by LCꢀMS, which suggests that benzylic alcohol was directly oxidized to acid possibly. In addition, we did not observe
corresponding aldehyde and any self coupled product by the possible in situ generated aldehyde and the unoxidized alcohol. After
the successful application of the oxidative methyl esterification from benzylic alcohols, we tried to extend this methodology to the
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1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
4
aldehydes or carboxylic acids as substrates. It is found that base is not necessary in the methyl esterification of aldehyde and the
amount of the oxidant could be reduced to six equivalents. Subsequently, various aldehyde derivatives were examined and
representative results were listed in Table 3. Generally, it can be seen that the electronic effect and steric effect were not significant.
In addition, substrates with electronꢀdonating groups were superior to those with electronꢀwithdrawing groups. The aldehydes
substituted with the electronꢀdonating group (methoxy) generated the methylation products in good to excellent yields under the
optimized reaction conditions (Table 3, entries 1ꢀ6). 2ꢀNaphthaldehyde was better than 1ꢀnaphthaldehyde, affording 96%, 72%
yields, respectively (Table 3, entries 7ꢀ8). Furthermore, many electronꢀwithdrawing groups, including cyano, nitro and ester, were
well tolerated under the standard conditions (Table 3, entries 9ꢀ11). To show the synthetic utility of this method, heteroaryl
aldehydes such as thiopheneꢀ2ꢀcarbaldehyde and 4ꢀ(1Hꢀimidazolꢀ1ꢀyl) benzaldehyde, were subjected to the optimized conditions,
and the desired esters (4h-4i) were obtained in satisfactory yields (Table 3, entries 12ꢀ13). It is observed that anthraceneꢀ10ꢀ
carbaldehyde could give the desired ester (4j) in 70% yield using our system (Table 3, entry 14).
a
TABLE 3. Copper-catalyzed methyl esterification of various aldehydes
O
O
Copper quinolate (20 mol%)
OMe
H
R
R
TBHP (1.8 mmol), TBAI (0.12 mmol)
o
DMSO, 120 C, air, 24 h
3
4
b
Entry
1
Aldehyde
Product
Yield (%)
95
MeO
CHO
OMe
CHO
MeO
MeO
COOMe
OMe
COOMe
2a
2b
2
3
88
61
MeO
MeO
MeO
MeO
4a
2c
4b
MeO
MeO
CHO
CHO
COOMe
COOMe
MeO
4
5
96
94
MeO
MeO
MeO
MeO
MeO
OMe
CHO
OMe
COOMe
MeO
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1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
OMe
CHO
OMe
6
7
MeO
MeO
MeO
MeO
COOMe
4c
85
CHO
COOMe
4d
4e
96
72
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
CHO
COOMe
8
9
MeOOC
NC
CHO
MeOOC
NC
COOMe
4f
69
71
1
0
1
CHO
CHO
COOMe
COOMe
4g
1
O
2
N
O
2
N
2h
69
S
S
1
1
2
3
CHO
COOMe
4h
4i
65
64
N
N
N
CHO
N
COOMe
COOMe
CHO
1
4
4j
70
a
Reaction conditions: aldehyde (0.3mmol), copper quinolate (0.06 mmol), TBHP (1.8mmol, 70% aqueous solution), TBAI (0.12
o
b
mmol), DMSO (2 mL), 120 C, Air, 24h. The yield based on aldehyde.
Comparing with aldehydes, the corresponding acids are cheaper and more stable. At the same time, it was found that less amount
o
of TBHP (0.9 mmol) and lower reaction temperature (100 C) were suitable for the methyl esterification of acids. It is noteworthy
that in this transformation, TBAI is not necessary. Thus, we can conclude that TABI do show acceleration role in the process of
oxidation. Then, different substituted acids were subjected to the optimized conditions as shown in Table 4. The results indicated
that the acids with electronꢀwithdrawing or electronꢀdonating groups were all well tolerated and provided the corresponding
products in good to excellent yields. Similar to aldehydes, the acids with the strong electronꢀdonating methoxyl group generated the
methylation products in good to excellent yields under the optimized reaction conditions (2a, 2d and 6a-6c). For the tertiary butyl
and methyl groups, the desired esters were produced smoothly in 84% and 60% yields respectively (6d and 2e). Good yields were
obtained when 1ꢀnaphthoic acid and 2ꢀnaphthoic acid were employed as the substrates (4d and 4e). A wide range of functional
groups, including phenyl, benzoyl, ethanoyl, cyano and nitro, all were performed smoothly under the optimized conditions (2h, 4g
and 6e-6l). To expand the synthetic utility of the method, various heteroaryl acids such as 1ꢀmethylꢀ1Hꢀindazoleꢀ3ꢀcarboxylic acid,
thiopheneꢀ2ꢀcarboxylic acid, 5ꢀbromofuranꢀ2ꢀcarboxylic acid and furanꢀ2ꢀcarboxylic acid, were subjected to the optimized
conditions and afforded the desired esters in moderate yields (4h, 6m and 6n). 3ꢀHydroxyꢀ2ꢀnaphthoic acid only gave 18% yield of
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the corresponding product (6o) under the standard condition. It is speculated that hydroxyl group is sensitive to oxidants possibly.
To our delight, 2ꢀbenzamidoacetic acid could give the desired ester (6p) in 73% yield without any protections. 2,2′ꢀDithiodibenzoic
acid and 1ꢀadamantane carboxylic acid could not afford the corresponding esters (6qꢀ6r) under the standard conditions.
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
a
TABLE 4. Copper-catalyzed methyl esterification of various acids
O
O
Copper quinolate (20 mol%)
TBHP (1.8 mmol)
OH
OMe
R
R
o
DMSO, 120 C, air, 24 h
5
6
OMe
COOMe
MeO
MeO
MeO
MeO
COOMe
COOMe
COOMe
OMe
6a, 85%
MeO
2d, 85%
Br
6b, 84%
2a, 99% (97%)
MeO
COOMe
COOMe
COOMe
COOMe
NO2
c, 92%
COOMe
6
6d, 84% (71%)
2e, 60%
4d, 92%
COOMe
O
COOMe
COOMe
4
e, 86%
6e, 93% (91%)
6f, 90%
6g, 98% (92%)
O N
2
O
COOMe
NO2
COOMe
O N
2
COOMe
COOMe
6j, 68%
6
h, 71%
COOMe
6i, 86% (83%)
2h, 88% (86%)
N
N
O N
S
2
NC
COOMe
COOMe
Cl
COOMe
6
k, 73%
4g, 63%
6l, 77%
4h, 51%
O
COOMe
Br
O
O
COOMe
N
COOMe
COOMe
H
OH
6o, 18%
6
m, 73%
6n, 44%
6p, 73%
MeOOC
COOMe
S
S
COOMe
6q, trace
6r, trace
a
Reaction conditions: Acid (0.3 mmol), copper quinolate (0.06 mmol), TBHP (1.8 mmol, 70% aqueous solution), DMSO (2 mL),
o
1
20 C, air, 24 h. The value in the parenthesis represents the result when less amount of TBHP (0.9 mmol) and lower reaction
o
temperature (100 C) were employed.
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Subsequently, 4ꢀformylbenzoic acid (7) was subjected to the optimized conditions and afforded the desired dimethyl ester (8) in
0% yield (Scheme 2). Then 1Hꢀindoleꢀ3ꢀcarboxylic acid was investigated and doubleꢀmethylation product (10) (39%), monoꢀ
6
methylation product (11) (27%), Nꢀmethylation product (12) (22%) were formed respectively (Scheme 3). 1ꢀMethylꢀ1Hꢀindoleꢀ3ꢀ
carboxylic acid (12) can give the desired ester (10) in 55% yield under the optimized condition, while 51% yield of Nꢀmethylation
0
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8
9
0
15
product (10) was formed by methyl 1Hꢀindoleꢀ3ꢀcarboxylate. Thus, it could be seen that our system can not only be used in the
methyl esterification of alcohol, aldehyde and acid, but also provide a protection method of Nꢀmethylation.
O
H
O
O
O
Copper quinolate (40 mol%)
TBHP (4.8 mmol), TBAI (0.24 mmol)
OH
MeO
OMe
o
DMSO, 120 C, air, 24 h
7
8, 60%
SCHEME 2. Copper-catalyzed methyl esterification of 4-formylbenzoic acid.
COOH
COOMe
+
COOMe
+
COOH
Copper quinolate
TBHP, DMSO
120 C, air, 24 h
N
N
N
N
o
H
H
9
10, 39%
11, 27%
12, 22%
COOH
COOMe
Copper quinolate (20 mol%)
TBHP (1.8 mmol)
N
o
DMSO, 120 C, air, 24 h
N
12
10, 55%
COOMe
COOMe
Copper quinolate (20 mol%)
TBHP (1.8 mmol)
N
o
DMSO, 120 C, air, 24 h
N
H
1
1
10, 51%
SCHEME 3. Copper-catalyzed methylation or methyl esterification of 1H-indole-3-carboxylic acid or its methyl ester.
Further investigations on the mechanism were performed (Scheme 4). The reaction of sodium 4ꢀmethoxybenzoate with TBHP
did not generate the methyl 4ꢀmethoxybenzoate, indicating that no 4ꢀmethoxybenzoate anion and methyl cation were generated in
the reaction system. In addition, it was observed that TEMPO could completely inhibit the reaction, which suggests that the
6
reaction may involve acyloxy and methyl radicals in the catalytic cycle of the ester synthesis. When DMSOꢀd replaced the solvent
1
DMSO, 96% yield of methyl 4ꢀmethoxybenzoate was obtained. H NMR showed that the product did not contain deuterium. This
is an indirect proof that the methyl group of product came from TBHP. When 1ꢀ(2ꢀhydroperoxypropanꢀ2ꢀyl) benzene was
employed instead of TBHP, methyl 4ꢀmethoxybenzoate was obtained in 88% yield. It is noteworthy that great amount of
acetophenone (13) was also isolated by column chromatography. This is a powerful proof to demonstrate that the methyl group of
product came from oxidant. We believed that tꢀbutyl naphthaleneꢀ1ꢀcarboperoxoate may exist in the reaction system as an
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intermediate. In order to prove this hypothesis, this peroxide was synthesized and employed as the substrate for the reaction. As
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8
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1
1
1
1
1
1
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1
1
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2
2
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4
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4
5
5
5
5
5
5
5
5
5
5
6
1
6
expected, the methyl 1ꢀnaphthoate (4e) was obtained in 87% yield.
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
O
Copper quinolate (20 mol%)
TBHP (1.8 mmol)
O
MeO
MeO
MeO
ONa
o
OMe
DMSO, 120 C, air, 24 h
trace
O
Copper quinolate (20 mol%)
TBHP (1.8 mmol)
O
MeO
OH
o
OMe
DMSO, 100 C, air, 24 h
No scavenger = 97%
TEMPO < 1%
BQ < 1%
O
OH
O
O
Copper quinolate (20 mol%)
MeO
MeO
MeO
6
o
DMSOꢀd , 120 C, air, 24 h
OMe
OH
2a, 96%
O
OH
Ph
O
O
O
Copper quinolate (20 mol%)
MeO
o
DMSO, 120 C, air, 24 h
Ph
Me
OH
OMe
2a, 88%
13
O
O
O
O
OMe
O
OH
Copper quinolate (20 mol%)
o
DMSO, 120 C, air, 24 h
4
e, 87%
SCHEME 4. Control experiments and effect of radical inhibitor.
Based on the above results and literatures, a tentative mechanism is illustrated in Scheme 5. Initially, TBHP decomposes to
17
generate the tertꢀbutoxyl and tertꢀbutylperoxy radicals in the presence of copper catalyst. Then, a facile unimolecular
18
decomposition of tertꢀbutoxyl to acetone and a methyl radical occurred. The benzylic alcohol was directly oxidized to benzoic
acid in the presence of oxidant and base, while the aldehyde was easily oxidized to benzoic aicd only using oxidant. Subsequently,
acyloxy radical was generated from benzoic acid in the function of tertꢀbutoxyl or tertꢀbutylperoxy radical. Finally, the coupling of
acyloxy radical and methyl radical gave the desired ester.
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2
2
2
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4
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5
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5
5
5
5
6
OHꢀ
tꢀBuOOH
tꢀBuO
CuI]
[CuII]
[
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
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7
8
9
0
1
2
3
4
5
6
7
8
9
0
OHꢀ
O
(a)
H O
tꢀBuOO
O
tꢀBuOOH
Me
2
KβꢀMe
(b)
DMSO
O
O
O
[O]
base
[
O]
R
OH
R
OH
R
R
H
O
(c)
O
O
tꢀBuO or tꢀBuOO
H
(d)
(e)
R
R
O
tꢀBuOH or tꢀBuOOH
O
Me
O
R
O
SCHEME 5. The possible mechanism.
Conclusions
In summary, we have successfully developed a novel, effective and direct method of copperꢀcatalyzed methyl esterification of
benzyl alcohols, aldehydes or acids via C–C cleavage reaction. It is noteworthy that in this transformation, TBHP was used not only
as the oxidant, but also as the source of methyl group. In general, the desired methyl esters could be obtained in good to excellent
yields. Thus, this catalytic protocol could tolerate a wide range of substrates, which represents a practical and lowꢀcost method for
the preparation of methyl ester based molecules. It could be the possible supplement for the traditional way in some cases. Further
investigations toward its applications are currently underway.
Experimental Section
General experimental: All manipulations were carried out under air atmosphere. Benzylic alcohols, aldehydes, acids, tertꢀbutyl
hydroperoxide (70% solution in water) and tetrabutylammonium iodide were commercially available and used without further
purification. Column chromatography was generally performed on silica gel (300ꢀ400 mesh) and reactions were monitored by thin
1
13
layer chromatography (TLC) using UV light to visualize the course of the reactions. The H NMR (400 MHz) and C NMR (100
MHz) data were recorded on 400 M spectrometers using CDCl as solvent. The chemical shifts (δ) are reported in ppm and
3
1
13
coupling constants (J) in Hz. H NMR spectra was recorded with tetramethylsilane (δ = 0.00 ppm) as internal reference; C NMR
spectra was recorded with CDCl (δ = 77.00 ppm) as internal reference.
3
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General procedure for copper-catalyzed methyl esterification of benzyl alcohol: benzylic alcohol (0.3 mmol), copper
quinolate (0.06 mmol, 20 mol %, 0.0210 g), K PO (0.6 mmol, 2 equiv, 0.1274 g), TBAI (0.12 mmol, 40 mol %, 0.0443 g), TBHP
3
4
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
(
2.4 mmol, 0.33 mL of a 70% aqueous solution), and DMSO (2.0 mL) were added to a test tube in air. The reaction mixture was
0
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7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
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5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
o
heated in an oil bath at 120 C for 24 h and was quenched with a saturated solution of Na SO (for removal of excess TBHP) and
2
3
extracted with ethyl acetate. The organic solvent was removed under vacuum and purification by chromatography on a silica gel
column by using a mixture of petroleum ether and ethyl acetate afforded the desired product.
General procedure for copper-catalyzed methyl esterification of aldehyde: aldehyde (0.3 mmol), copper quinolate (0.06
mmol, 20 mol %, 0.0210 g), TBAI (0.12 mmol, 40 mol %, 0.0443 g), TBHP (1.8 mmol, 0.25 mL of a 70% aqueous solution), and
o
DMSO (2.0 mL) were added to a test tube in air. The reaction mixture was heated in an oil bath at 120 C for 24 h and was
quenched with a saturated solution of Na SO (for removal of excess TBHP) and extracted with ethyl acetate. The organic solvent
2
3
was removed under vacuum and purification by chromatography on a silica gel column by using a mixture of petroleum ether and
ethyl acetate afforded the desired product.
General procedure for copper-catalyzed methyl esterification of acid: acid (0.3 mmol), copper quinolate (0.06 mmol, 20
mol %, 0.0210 g), TBHP (1.8 mmol, 0.25 mL of a 70% aqueous solution), and DMSO (2.0 mL) were added to a test tube in air.
o
The reaction mixture was heated in an oil bath at 100ꢀ120 C for 24 h and was quenched with a saturated solution of Na SO (for
2
3
removal of excess TBHP) and extracted with ethyl acetate. The organic solvent was removed under vacuum and purification by
chromatography on a silica gel column by using a mixture of petroleum ether and ethyl acetate afforded the desired product.
1
Methyl 4-isopropylbenzoate (32.6 mg, 61%): H NMR (400 MHz, CDCl ) (δ, ppm) 7.96 (d, J = 8.0 Hz, 2H), 7.29 (d, J = 8.0
3
13
Hz, 2H), 3.90 (s, 3H), 3.01ꢀ2.89 (m, 1H), 1.27 (s, 3H), 1.25 (s, 3H); C NMR (100 MHz, CDCl ) (δ, ppm) 167.1, 154.2, 129.6,
3
+
127.7, 126.4, 51.9, 34.2, 30.8, 23.6; MS: Anal. Calcd. For C H O : 179.1, Found: 179.1 (M+1) .
11
15
2
1
Methyl 3,5-dimethoxybenzoate (51.3 mg, 96%): H NMR (400 MHz, CDCl ) (δ, ppm) 7.18 (d, J = 4.0 Hz, 2H), 6.64 (t, J = 4,.0
3
1
3
Hz, 1H), 3.90 (s, 3H), 3.82 (s, 6H); C NMR (100 MHz, CDCl ) (δ, ppm) 166.7, 160.5, 131.9, 107.0, 105.6, 55.4, 52.1; MS: Anal.
3
+
Calcd. For C H O : 197.1, Found: 197.1 (M+1) .
10
13
4
1
Methyl 4-nitrobenzoate (47.8 mg, 88%): H NMR (400 MHz, CDCl ) (δ, ppm) 8.26 (d, J =8.0 Hz, 2H), 8.18 (d, J = 8.0 Hz,
3
13
2
1
H), 3.96 (s, 3H); C NMR (100 MHz, CDCl ) (δ, ppm) 165.4, 150.7, 135.7, 130.9, 123.7, 53.1; MS: Anal. Calcd. For C H NO :
3
8
8
4
+
82.0, Found: 182.0 (M+1) .
Methyl 4-methylbenzoate (33.3 mg, 74%): H NMR (400 MHz, CDCl ) (δ, ppm) 7.93 (d, J = 8.0 Hz, 2H), 7.23 (d, J = 8.0 Hz,
1
3
1
3
2H), 3.89 (s, 3H), 2.39 (s, 3H); C NMR (100 MHz, CDCl ) (δ, ppm) 166.1, 142.5, 128.5, 128.0, 126.4, 50.9, 20.6; MS: Anal.
3
+
Calcd. For C H O : 151.1, Found: 151.1 (M+1) .
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2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
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4
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4
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Methyl 3-phenoxybenzoate (45.9 mg, 67%): H NMR (400 MHz, CDCl ) (δ, ppm) 7.77 (d, J = 8.0 Hz, 1H), 7.66 (s, 1H), 7.37
3
13
(
dt, J = 16.0, 7.9 Hz, 3H), 7.20 (d, J = 8.0 Hz, 1H), 7.13 (t, J = 8.0 Hz, 1H), 7.01 (d, J = 8.0 Hz, 2H), 3.88 (s, 3H); C NMR (100
MHz, CDCl ) (δ, ppm) 166.4, 157.4, 156.6, 131.8, 129.8, 129.7, 124.2, 123.7, 123.2, 119.5, 119.0, 52.2; MS: Anal. Calcd. For
3
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
+
C H O : 229.1, Found: 229.1 (M+1) .
1
4
13
3
1
Methyl 2,4-dimethoxybenzoate (52.3 mg, 88%): H NMR (400 MHz, CDCl ) (δ, ppm) 7.85 (d, J = 8.0 Hz, 1H), 6.51–6.45 (m,
3
1
3
2H), 3.89 (s, 3H), 3.85 (s, 3H), 3.84 (s, 3H); C NMR (100 MHz, CDCl ) (δ, ppm) 166.0, 164.2, 161.2, 133.7, 112.0, 104.5, 98.8,
3
+
55.8, 55.3, 51.6; MS: Anal. Calcd. For C H O : 197.1, Found: 197.1 (M+1) .
1
0
13
4
1
13
Methyl 3,4,5-trimethoxybenzoate (57.7 mg, 85%): H NMR (400 MHz, CDCl ) (δ, ppm) 7.24 (s, 2H), 3.85 (s, 12H); C NMR
3
(
100 MHz, CDCl ) (δ, ppm) 166.8, 153.1, 142.2, 125.3, 106.9, 61.1, 56.4, 52.4; MS: Anal. Calcd. For C H O : 227.1, Found:
3
11 15
5
+
2
27.1 (M+1) .
Methyl 4-methoxybenzoate (49.3 mg, 99%): H NMR (400 MHz, CDCl ) (δ, ppm) 7.99 (d, J = 8.0 Hz, 2H), 6.91 (d, J = 8.0 Hz,
1
3
1
3
2
H), 3.88 (s, 3H), 3.85 (s, 3H); C NMR (100 MHz, CDCl ) (δ, ppm) 167.0, 163.5, 131.8, 122.8, 113.8, 55.6, 52.0; MS: Anal.
3
+
Calcd. For C H O : 167.1, Found: 167.1 (M+1) .
9
11
3
1
13
Dimethyl terephthalate (34.9 mg, 60%): H NMR (400 MHz, CDCl ) (δ, ppm) 8.08 (s, 4H), 3.93 (s, 6H); C NMR (100 MHz,
3
13
CDCl ) (δ, ppm) 166.5, 134.07, 129.7, 110.0, 52.7; C NMR (100 MHz, CDCl ) (δ, ppm) 166.5, 134.1, 129.7, 110.0, 52.7; MS:
3
3
+
Anal. Calcd. For C H O : 195.1, Found: 195.1 (M+1) .
1
0
11
4
1
Methyl 4-cyanobenzoate (34.3 mg, 71%): H NMR (400 MHz, CDCl ) (δ, ppm) 8.15 (d, J = 8.0 Hz, 2H), 7.76 (d, J = 8.0 Hz,
3
13
2
H), 3.97 (s, 3H); C NMR (100 MHz, CDCl ) (δ, ppm) 165.3, 133.8, 132.2, 130.0, 117.9, 116.3, 52.7; MS: Anal. Calcd. For
3
+
C H NO : 162.1, Found: 162.1 (M+1) .
9
8
2
1
Methyl 2-naphthoate (53.6 mg, 96%): H NMR (400 MHz, CDCl ) (δ, ppm) 8.59 (S, 1H), 8.05 (dd, J = 8.6, 1.4 Hz, 1H), 7.92
3
13
(d, J = 8.0 Hz, 1H), 7.85 (d, J = 8.0 Hz, 2H), 7.58–7.49 (m, 2H), 3.96 (s, 3H); C NMR (100 MHz, CDCl ) (δ, ppm) 167.5, 135.7,
3
+
1
32.7, 131.3, 129.6, 128.5, 128.4, 128.0, 127.6, 126.9, 125.4, 52.5; MS: Anal. Calcd. For C H O : 187.1, Found: 187.1 (M+1) .
12 11
2
1
Methyl thiophene-2-carboxylate (21.7 mg, 51%): H NMR (400 MHz, CDCl ) (δ, ppm) 7.88 (dd, J = 3.7, 0.8 Hz, 1H), 7.63 (dd,
3
13
J = 4.9, 0.8 Hz, 1H), 7.18 (dd, J = 4.7, 4.0 Hz, 1H), 3.97 (s, 3H); C NMR (100 MHz, CDCl ) (δ, ppm) 162.9, 133.7, 133.6, 132.6,
3
+
1
28.0, 52.4; MS: Anal. Calcd. For C H SO : 143.0, Found: 143.0 (M+1) .
6
7
2
1
Methyl 3,4-dimethoxybenzoate (35.9 mg, 61%): H NMR (400 MHz, CDCl ) (δ, ppm) 7.68 (dd, J = 8.4, 1.9 Hz, 1H), 7.55 (d, J
3
13
= 4.0 Hz, 1H), 6.89 (d, J = 8.0 Hz, 1H), 3.94 (s, 3H), 3.90 (s, 6H); C NMR (100 MHz, CDCl ) (δ, ppm) 167.1, 153.1, 148.8,
3
+
123.8, 122.8, 112.1, 110.4, 56.2, 52.2; MS: Anal. Calcd. For C H O : 197.1, Found: 197.1 (M+1) .
10
13
4
1
Methyl 1-naphthoate (40.2 mg, 72%): H NMR (400 MHz, CDCl ) (δ, ppm) 8.91 (d, J = 8.0 Hz, 1H), 8.18 (d, J = 8.0 Hz, 1H),
3
13
8
.01 (d, J = 8.0 Hz, 1H), 7.87 (d, J = 8.0 Hz, 1H), 7.64–7.58 (m, 1H), 7.56–7.45 (m, 2H), 3.99 (s, 3H); C NMR (100 MHz, CDCl3)
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(
δ, ppm) 168.3, 134.0, 133.6, 131.5, 130.5, 128.8, 129.0, 127.3, 126.4, 126.0, 124.7, 52.4; MS: Anal. Calcd. For C H O : 187.1,
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
12 11 2
+
Found: 187.1 (M+1) .
1
Methyl anthracene-10-carboxylate (49.6 mg, 70%): H NMR (400 MHz, CDCl ) (δ, ppm) 8.51 (s, 1H), 8.01 (t, J = 8.0 Hz, 4H),
3
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
13
7
1
.50 (dt, J = 14.7, 7.0 Hz, 4H), 4.17 (s, 3H); C NMR (100 MHz, CDCl ) (δ, ppm) 170.3, 134.4, 133.7, 131.2, 129.7, 128.9, 128.7,
3
+
27.5, 127.3, 125.7, 125.3, 124.0, 122.5, 122.4, 121.3, 52.9; MS: Anal. Calcd. For C H O : 237.1, Found: 237.1 (M+1) .
1
6
13
2
1
Methyl 2,3,4-trimethoxybenzoate (67.8 mg, 94%): H NMR (400 MHz, CDCl ) (δ, ppm) 7.56 (d, J = 8.0 Hz, 1H), 6.66 (d, J =
3
1
3
8.0 Hz, 1H), 3.89 (s, 3H), 3.86 (s, 3H), 3.84 (s, 3H), 3.83 (s, 3H); C NMR (100 MHz, CDCl ) (δ, ppm) 166.2, 157.3, 154.8, 143.1,
3
+
1
27.1, 124.4, 107.1, 62.0, 61.2, 56.2, 52.1; MS: Anal. Calcd. For C H O : 227.1, Found: 227.1 (M+1) .
11 15
5
1
Methyl 2,4,5-trimethoxybenzoate (57.7 mg, 85%): H NMR (400 MHz, CDCl ) (δ, ppm) 7.41 (s, 1H), 6.54 (s, 1H), 3.94 (s,
3
13
3
5
H), 3.91 (s, 3H), 3.88 (s, 6H); C NMR (100 MHz, CDCl ) (δ, ppm) 165.9, 155.5, 153.4, 142.3, 114.1, 110.2, 97.4, 56.8, 56.2,
3
+
5.9, 51.7; MS: Anal. Calcd. For C H O : 227.1, Found: 227.1 (M+1) .
1
1
15
5
1
Methyl 4-(1H-imidazol-1-yl)benzoate (38.8 mg, 64%): H NMR (400 MHz, CDCl ) (δ, ppm) 8.16 (d, J = 8.0 Hz, 2H), 7.97 (s,
3
13
1H), 7.48 (d, J = 8.0 Hz, 2H), 7.37 (s, 1H), 7.24 (s, 1H), 3.95 (s, 3H); C NMR (100 MHz, CDCl ) (δ, ppm) 165.9, 140.5, 135.3,
3
+
131.4, 130.9, 128.8, 120.4, 117.6, 52.3; MS: Anal. Calcd. For C H N O : 203.1, Found: 203.1 (M+1) .
1
1
11
2
2
1
Methyl 2-nitrobenzoate (46.7 mg, 86%): H NMR (400 MHz, CDCl ) (δ, ppm) 7.92 (dd, J = 7.8, 1.1 Hz, 1H), 7.75 (dd, J = 7.5,
3
1
3
1
1
.5 Hz, 1H), 7.67 (dtd, J = 17.0, 7.4, 1.5 Hz, 2H), 3.93 (s, 3H); C NMR (100 MHz, CDCl ) (δ, ppm) 166.1, 133.2, 132.0, 130.0,
3
+
29.3, 127.7, 124.1, 53.5; MS: Anal. Calcd. For C H NO : 182.0, Found: 182.0 (M+1) .
8
8
4
1
Methyl 4-tert-butylbenzoate (48.4 mg, 84%): H NMR (400 MHz, CDCl ) (δ, ppm) 7.97 (d, J = 8.0 Hz, 2H), 7.45 (d, J = 8.0 Hz,
3
1
3
2
H), 3.90 (s, 3H), 1.33 (s, 9H); C NMR (100 MHz, CDCl ) (δ, ppm) 167.3, 156.7, 129.6, 127.6, 125.5, 52.2, 32.3, 31.3; MS:
3
+
Anal. Calcd. For C H O : 193.1, Found: 193.1 (M+1) .
1
2
17
2
1
Methyl 3-nitrobenzoate (36.9 mg, 68%): H NMR (400 MHz, CDCl ) (δ, ppm) 8.88–8.83 (m, 1H), 8.45–8.40 (m, 1H), 8.40–
3
1
3
8
1
.35 (m, 1H), 7.68 (t, J = 8.0 Hz, 1H), 4.00 (s, 3H); C NMR (100 MHz, CDCl ) (δ, ppm) 165.1, 148.4, 135.5, 132.0, 129.9, 127.6,
3
+
24.8, 53.0; MS: Anal. Calcd. For C H NO : 182.1, Found: 182.1 (M+1) .
8
8
4
1
Methyl 2-phenylbenzoate (59.2 mg, 93%): H NMR (400 MHz, CDCl ) (δ, ppm) 7.81 (dd, J = 7.7, 0.7 Hz, 1H), 7.50 (td, J =
3
13
7
1
.5, 1.2 Hz, 1H), 7.37 (dt, J = 13.3, 6.8 Hz, 5H), 7.32–7.28 (m, 2H), 3.61 (s, 3H); C NMR (100 MHz, CDCl ) (δ, ppm) 169.4,
3
42.7, 141.5, 131.5, 131.1, 131.0, 130.0, 128.5, 128.3, 127.5, 127.4, 52.2; MS: Anal. Calcd. For C H O : 213.1, Found: 213.1
1
4
13
2
+
(M+1) .
Methyl 2-benzoylbenzoate (70.6 mg, 98%): H NMR (400 MHz, CDCl ) (δ, ppm) 8.04 (d, J = 8.0 Hz, 1H), 7.75 (d, J = 8.0 Hz,
1
3
1
3
2
H), 7.63 (t, J = 8.0 Hz, 1H), 7.59–7.51 (m, 2H), 7.45–7.38 (m, 3H), 3.60 (s, 3H); C NMR (100 MHz, CDCl ) (δ, ppm) 197.3,
3
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3
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66.6, 141.9, 137.3, 133.3, 132.7, 130.3, 129.9, 129.4, 129.3, 128.7, 128.0, 52.4; MS: Anal. Calcd. For C H O : 241.1, Found:
15 13 3
+
41.1 (M+1) .
1
Methyl 5-bromofuran-2-carboxylate (44.7 mg, 73%): H NMR (400 MHz, CDCl ) (δ, ppm) 7.14 (d, J = 4.0 Hz, 1H), 6.47 (d, J
3
0
1
2
3
4
5
6
7
8
9
0
1
2
3
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7
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8
9
0
1
2
3
4
5
6
7
8
9
0
13
=
4.0 Hz, 1H), 3.90 (s, 3H); C NMR (100 MHz, CDCl ) (δ, ppm) 158.2, 146.3, 127.7, 120.3, 114.1, 52.3; MS: Anal. Calcd. For
3
+
C H BrO : 205.0, Found: 205.0 (M+1) .
6
6
3
1
Methyl 4-acetylbenzoate (37.9 mg, 71%): H NMR (400 MHz, CDCl ) (δ, ppm) 8.12 (d, J = 8.0 Hz, 2H), 8.01 (d, J = 8.0 Hz,
3
1
3
2H), 3.95 (s, 3H), 2.65 (s, 3H); C NMR (100 MHz, CDCl ) (δ, ppm) 197.4, 166.1, 140.1, 133.8, 129.7, 128.1, 52.4, 26.8; MS:
3
+
Anal. Calcd. For C H O : 179.1, Found: 179.1 (M+1) .
10 11
3
1
Methyl 2,6-dimethoxybenzoate (50.0 mg, 85%): H NMR (400 MHz, CDCl ) (δ, ppm) 7.25 (t, J = 8.0 Hz, 1H), 6.53 (d, J = 8.0
3
13
Hz, 2H), 3.88 (s, 3H), 3.78 (s, 6H); C NMR (100 MHz, CDCl ) (δ, ppm) 167.3, 157.5, 131.3, 113.1, 104.1, 56.2, 52.7; MS: Anal.
3
+
Calcd. For C H O : 197.1, Found: 197.1 (M+1) .
10
13
4
1
Methyl 5-methoxy-2-nitrobenzoate (58.3 mg, 92%): H NMR (400 MHz, CDCl ) (δ, ppm) 8.04–8.02 (m, 1H), 7.04–7.01 (m,
3
1
3
2H), 3.93 (s, 3H), 3.92 (s, 3H); C NMR (100 MHz, CDCl ) (δ, ppm) 166.8, 163.6, 140.0, 131.4, 126.9, 115.9, 114.3, 56.4, 53.6;
3
+
MS: Anal. Calcd. For C H NO : 212.1, Found: 212.1 (M+1) .
9
10
5
1
Methyl 3-hydroxy-2-naphthoate (10.9 mg, 18%): H NMR (400 MHz, CDCl ) (δ, ppm) 10.44 (s, 1H), 8.49 (s, 1H), 7.80 (d, J =
3
13
8
.0 Hz, 1H), 7.68 (d, J = 8.0 Hz, 1H), 7.50 (t, J = 8.0 Hz, 1H), 7.33 (d, J = 12.0 Hz, 2H), 4.03 (s, 3H); C NMR (100 MHz, CDCl3)
(δ, ppm) 169.3, 155.2, 136.9, 131.4, 128.2, 128.1, 126.0, 125.3, 122.9, 113.1, 110.6, 51.6; MS: Anal. Calcd. For C H O : 203.1,
12
11
3
+
Found: 203.1 (M+1) .
Methyl 2-bromo-5-methoxybenzoate (61.5 mg, 84%): H NMR (400 MHz, CDCl ) (δ, ppm) 7.49 (d, J = 9.0 Hz, 1H), 7.28 (d, J
1
3
13
= 3.0 Hz, 1H), 6.86 (dd, J = 8.8, 3.1 Hz, 1H), 3.90 (s, 3H), 3.78 (s, 3H); C NMR (100 MHz, CDCl ) (δ, ppm) 166.7, 158.7, 135.2,
3
+
132.8, 119.2, 116.4, 112.1, 55.8, 528; MS: Anal. Calcd. For C H BrO : 245.0, Found: 245.0 (M+1) .
9
10
3
1
Methyl 2-chloro-4-nitrobenzoate (47.1 mg, 73%): H NMR (400 MHz, CDCl ) (δ, ppm) 8.31 (d, J = 2.0 Hz, 1H), 8.16 (dd, J =
3
13
8
1
.6, 2.2 Hz, 1H), 7.98 (d, J = 8.0 Hz, 1H), 4.00 (s, 3H); C NMR (100 MHz, CDCl ) (δ, ppm) 164.8, 149.6, 135.9, 135.0, 132.2,
3
+
26.2, 121.6, 53.3; MS: Anal. Calcd. For C H ClNO : 216.0, Found: 216.0 (M+1) .
8
7
4
1
Methyl 1-methyl-1H-indazole-3-carboxylate (43.9 mg, 77%): H NMR (400 MHz, CDCl ) (δ, ppm) 8.21 (d, J = 8.0 Hz, 1H),
3
13
7
.44 (d, J = 4.0 Hz, 2H), 7.35–7.27 (m, 1H), 4.15 (s, 3H), 4.04 (s, 1H); C NMR (100 MHz, CDCl ) (δ, ppm) 163.2, 141.1, 134.5,
3
+
127.1, 123.8, 123.3, 122.2, 109.7, 52.2, 36.6; MS: Anal. Calcd. For C H N O : 191.1, Found: 191.1 (M+1) .
10
11
2
2
1
Methyl 4-phenylbenzoate (57.3 mg, 90%): H NMR (400 MHz, CDCl ) (δ, ppm) 8.12 (d, J = 8.0 Hz, 2H), 7.69–7.60 (m, 4H),
3
13
7
1
.47 (t, J = 8.0 Hz, 2H), 7.40 (t, J = 8.0 Hz, 1H), 3.94 (s, 3H); C NMR (100 MHz, CDCl ) (δ, ppm) 167.2, 145.8, 140.2, 130.3,
3
+
29.2, 129.1, 128.4, 127.5, 127.3, 52.4; MS: Anal. Calcd. For C H O : 213.1, Found: 213.1 (M+1) .
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Methyl furan-2-carboxylate (16.6 mg, 44%): H NMR (400 MHz, CDCl ) (δ, ppm) 7.59 (s, 1H), 7.19 (d, J = 4.0 Hz, 1H),
3
1
3
6
.55–6.50 (m, 1H), 3.90 (s, 3H); C NMR (100 MHz, CDCl ) (δ, ppm) 159.4, 146.5, 144.8, 118.2, 112.1, 52.2; MS: Anal. Calcd.
3
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
+
For C H O : 127.1, Found: 127.1 (M+1) .
6
7
3
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
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1
2
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7
8
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2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
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0
1
Methyl 2-benzamidoacetate (42.3 mg, 73%): H NMR (400 MHz, CDCl ) (δ, ppm) 7.82 (d, J = 8.0 Hz, 2H), 7.49 (t, J = 8.0 Hz,
3
13
1
H), 7.41 (t, J = 8.0 Hz, 2H), 7.15 (s, 1H), 4.21 (d, J = 8.0 Hz, 2H), 3.76 (s, 3H); C NMR (100 MHz, CDCl ) (δ, ppm) 170.8,
3
+
167.9, 133.8, 132.0, 128.8, 127.3, 52.6, 41.9; MS: Anal. Calcd. For C H NO : 194.1, Found: 194.1 (M+1) .
1
0
12
3
1
Methyl 1-methyl-1H-indole-3-carboxylate (31.2 mg, 55%): H NMR (400 MHz, CDCl ) (δ, ppm) 8.17 (dd, J = 5.7, 3.1 Hz,
3
13
1
1
H), 7.77 (s, 1H), 7.36–7.25 (m, 3H), 3.91 (s, 3H), 3.82 (s, 3H); C NMR (100 MHz, CDCl ) (δ, ppm) 165.7, 137.4, 135.4, 126.8,
3
+
23.0, 122.1, 121.9, 110.0, 107.1, 51.2, 33.7; MS: Anal. Calcd. For C H NO : 190.1, Found: 190.1 (M+1) .
11
12
2
1
Methyl 1H-indole-3-carboxylate (14.2 mg, 27%): H NMR (400 MHz, CDCl ) (δ, ppm) 9.21 (s, 1H), 8.18 (d, J = 4.5 Hz, 1H),
3
13
7
1
.92 (s, 1H), 7.44 (s, 1H), 7.26 (s, 2H), 3.93 (s, 3H); C NMR (100 MHz, DMSO) (δ, ppm) 165.2, 136.8, 132.9, 126.1, 122.8,
+
21.7, 120.8, 112.8, 106.7, 51.1; MS: Anal. Calcd. For C H NO : 176.1, Found: 176.1 (M+1) .
10
10
2
1
1-Methyl-1H-indole-3-carboxylic acid (11.6 mg, 22%): H NMR (400 MHz, CDCl ) (δ, ppm) 8.26–8.21 (m, 1H), 7.89 (s, 1H),
3
1
3
7.35 (dd, J = 20.9, 6.8 Hz, 3H), 3.87 (s, 3H); C NMR (100 MHz, DMSO) (δ, ppm) 170.8, 142.1, 141.2, 131.5, 127.3, 126.4,
+
1
25.8, 115.7, 111.3, 38.1; MS: Anal. Calcd. For C H NO : 176.1, Found: 176.1 (M+1) .
10 10
2
1
Acetophenone (90.1 mg, 42%): H NMR (400 MHz, CDCl ) (δ, ppm) 7.92 (d, J = 8.0 Hz, 2H), 7.51 (d, J = 68.0 Hz, 1H), 7.42
3
13
(
d, J = 8.0 Hz, 2H), 2.54 (s, 3H); C NMR (100 MHz, CDCl ) (δ, ppm) 197.8, 136.7, 132.8, 128.3, 128.0, 26.3; MS: Anal. Calcd.
3
+
For C H O: 121.1, Found: 121.1 (M+1) .
8
9
ACKNOWLEDGMENT. We are grateful to the grants from the International S&T Cooperation Program of Jiangsu Province
(
BZ2010048), the Scientific Research Foundation for the Returned Overseas Chinese Scholars, State Education Ministry, the
Priority Academic Program Development of Jiangsu Higher Education Institutions, and the Key Laboratory of Organic Synthesis of
Jiangsu Province.
Supporting Information Available: Procedural and spectral data. This material is available free of charge via the Internet at
http://pubs.acs.org.
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Chem. 2003, 68, 2944–2947; (c) Rout, S. K.; Ghara, K. K.; Banerjee, A.; Patel, B. K. Org. Lett. 2012, 14, 3982–3985; (d) Majji,
G.; Guin, S.; Gogoi, A.; Rout, S. K.; Patel, B. K. Chem. Commun. 2013, 49, 3031–3033.
(15) During our submission, we just found an example of copperꢀcatalyzed Nꢀmethylation using TBHP. Please see: Xia, Q.; Liu, X.;
Zhang, Y.; Chen, C.; Chen, W. Org. Lett. 2013, 15, 3326–3329.
(
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Zhang, J.; Chen, S.; Shi, E.; Xu, Y.; Wan, X. Angew. Chem. Int. Ed. 2012, 51, 1–6.
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