Facile preparation of aromatic esters from aromatic bromides with ethyl formate or DMF and molecular iodine via aryllithium

Article abstract of DOI:10.1016/j.tet.2012.04.016

Various aromatic bromides were treated with n-BuLi and subsequently with ethyl formate, followed by the reaction with ethanol and molecular iodine in the presence of K₂CO₃ to provide the corresponding aromatic ethyl esters in good yields. Moreover, aromatic bromides could be transformed into the corresponding aromatic methyl esters in good yields by the treatment with n-BuLi and subsequently with DMF, followed by the reaction with methanol, molecular iodine, and K₂CO₃. Some aromatics could be also converted into the corresponding aromatic esters in good yields by the treatment with n-BuLi, and subsequently with ethyl formate or DMF, followed by the reaction with molecular iodine and K₂CO₃. The present reactions offer a novel route for the transition-metal-free, carbon-monoxide-free, and therefore environmentally benign one-pot conversion of aromatic bromides and aromatics into aromatic esters.

Full text of DOI:10.1016/j.tet.2012.04.016

Tetrahedron 68 (2012) 4701e4709
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Facile preparation of aromatic esters from aromatic bromides with ethyl formate
or DMF and molecular iodine via aryllithium
*
Sousuke Ushijima, Katsuhiko Moriyama, Hideo Togo
Graduate School of Science, Chiba University, Yayoi-cho 1-33, Inage-ku, Chiba 263-8522, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Various aromatic bromides were treated with n-BuLi and subsequently with ethyl formate, followed by
the reaction with ethanol and molecular iodine in the presence of K2CO3 to provide the corresponding
aromatic ethyl esters in good yields. Moreover, aromatic bromides could be transformed into the cor-
responding aromatic methyl esters in good yields by the treatment with n-BuLi and subsequently with
DMF, followed by the reaction with methanol, molecular iodine, and K2CO3. Some aromatics could be
also converted into the corresponding aromatic esters in good yields by the treatment with n-BuLi, and
subsequently with ethyl formate or DMF, followed by the reaction with molecular iodine and K2CO3. The
present reactions offer a novel route for the transition-metal-free, carbon-monoxide-free, and therefore
environmentally benign one-pot conversion of aromatic bromides and aromatics into aromatic esters.
Ó 2012 Elsevier Ltd. All rights reserved.
Received 9 March 2012
Received in revised form 2 April 2012
Accepted 3 April 2012
Available online 12 April 2012
1. Introduction
bis(diisopropylphosphino)-ferrocene]-catalyzed carbonylation of
aromatic bromides with 9-methylfluorene-9-carbonylchloride as
Aromatic esters are very important and useful building blocks or
structural elements for the manufacture of pharmaceuticals and
agrochemicals.1 Generally, aromatic esters are prepared by the
condensation of aromatic carboxylic acids and alcohols, using the
Fischer esterification2aec and the Mitsunobu reaction.2cee In addi-
the CO precursor,3j were reported. However, there are still several
drawbacks, such as the use of expensive palladium catalyst, toxic
CO gas, the use of complicated operational treatment and equip-
ments, etc. As an alternative method, the halogen-metal exchange
of aryl halides, followed by the treatment with ethyl chlor-
oformate,4a dimethyl carbonate (preparation of methyl 4-
trimethylsilylbenzoate),4b or di-tert-butyl dicarbonate4c was
reported. However, there are still some shortcomings, such as
variable yields and totally low yields, and the troublesome prepa-
ration of ate-complexes. In order to realize an environmentally
benign, less toxic, inexpensive, and practical organic synthesis, the
preparation of aromatic esters from easily available substrates, such
as aromatic bromides, without the use of any transition metals
under mild conditions is required. Previously, we reported the
conversion of aromatic bromides and iodides into the corre-
sponding aromatic nitriles in good yields by the treatment with n-
BuLi and subsequently with DMF, followed by the treatment with
molecular iodine in aq NH3.5 The same treatment of typical aro-
matics and heteroaromatics with n-BuLi and subsequently with
DMF, followed by the treatment with molecular iodine in aq NH3,
also provided the corresponding aromatic nitriles in good yields. As
part of our ongoing study on the use of molecular iodine for organic
synthesis,6 we would like to report a facile method for the prepa-
ration of aromatic esters, which involves the reaction of aromatic
bromides or aromatics with n-BuLi, followed by the treatment with
formate esters or DMF, and finally with molecular iodine in the
presence of K2CO3 in alcohols.
tion, the Favorskii rearrangement of a-haloketones in the presence
of a base,2f the BaeyereVilliger oxidation of ketones with perox-
ides,2g and the Pinner reaction of nitriles with an alcohol2h are also
used. On the other hand, the preparation of aromatic esters from
aromatic bromides through carbonylation is very attractive in view
of synthetic organic chemistry. Today, transition-metal-catalyzed
reactions that yield of aromatic esters from aromatic halides have
been well studied3aec and recently, the Pd(OAc)2/dcpp$2HBF4-cat-
alyzed carbonylation of aromatic chlorides in the presence of al-
cohol under CO atmosphere,3d the Pd(OAc)2/xantphos-catalyzed
carbonylation of aromatic bromides in the presence of methanol
under CO atmosphere,3e the Pd(OAc)2/Cy2PCH2CH2CH2PCy2-cata-
lyzed carbonylation of aryl tosylates in the presence of t-BuOH
under CO atmosphere,3f the Pd(TFA)2/dppp-catalyzed decarbox-
ylative coupling of potassium oxalate monoester with aromatic
bromides,3g the Pd(OAc)2/Ad2BuP-catalyzed carbonylation of aro-
matic bromides in the presence of phenols under CO atmosphere,3h
the PdCl2/rac-BINAP-catalyzed carbonylation of aromatic bromides
in t-BuOH under CO atmosphere,3i and the Pd(dba)2/[1,10-
* Corresponding author. Tel./fax: þ81 43 290 2792; e-mail address: togo@facul-
ty.chiba-u.jp (H. Togo).
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2012.04.016

4702
S. Ushijima et al. / Tetrahedron 68 (2012) 4701e4709
Table 1
2. Results and discussion
Investigation for the third-step reaction conditions
At first, p-bromochlorobenzene and benzofuran were treated
with n-BuLi, followed by the reaction with ethyl chloroformate to
generate the corresponding esters, as shown in Scheme 1. However,
the esters were obtained in low yields, respectively, and instead,
the corresponding diaryl ketones and diarylmethanol were formed
as the major products. Thus, the present method is not practical for
the preparation of esters from aromatic bromides and aromatics.
Then, we looked into the possibility of treating p-bromo-
chlorobenzene with n-BuLi, followed by the reaction with ethyl
formate to generate an adduct. The adduct was subsequently
treated with molecular iodine and K2CO3 to provide ethyl p-
chlorobenzoate in 38% yield, together with p-chlorobenzaldehyde
in 37% yield, as shown in Table 1 (entry 1). As the key step was the
third reaction step, i.e., the effective oxidation of the HCO2Et-ad-
duct, optimization study of the third reaction step was carried out
as follows. Organic bases, such as triethylamine, diisopropylethyl-
amine, DBU, and pyridine, showed the same reactivity as K2CO3
(entries 4e7). However, the yield of ethyl p-chlorobenzoate was
increased and that of p-chlorobenzaldehyde was decreased when
EtOH was added in the third reaction step, together with molecular
iodine and K2CO3 (entries 8e12). Nevertheless, even if the amount
of EtOH was increased to 6 mL and the reaction temperature in the
third step was raised, the yield of ethyl p-chlorobenzoate could not
be improved much (entry 13).
Entry
Oxidant
(x equiv)
Base (y equiv)
EtOH
(z mL)
Time
(h)
Temp
(ꢁC)
Yield (%)
1
2
3
4
5
6
7
8
I2 (1.2)
I2 (1.2)
I2 (1.2)
I2 (1.2)
I2 (1.2)
I2 (1.2)
I2 (1.2)
I2 (1.6)
I2 (1.6)
I2 (1.6)
I2 (1.6)
I2 (1.6)
I2 (1.6)
I2 (1.6)
I2 (1.6)
I2 (1.6)
I2 (1.6)
d
K2CO3 (1.2)
K2CO3 (1.2)
K2CO3 (3.0)
NEt3 (1.2)
0
0
0
0
0
0
0
0.5
1.0
1.0
1.0
3.0
6.0
3.0
3.0
3.0
3.0
3.0
3.0
3.0
3.0
3.0
14
14
42
14
14
14
14
14
14
14
14
14
14
14
14
14
14
14
14
14
14
14
rt
50
rt
rt
rt
rt
rt
rt
rt
40
70
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
38 (37)a
38 (37)a
37 (36)a
18 (50)a
35 (24)a
34 (17)a
37 (36)a
59 (18)a
63 (17)a
57 (19)a
56 (19)a
68 (12)a
66 (12)a
45 (28)a
70 (6)a
iPr2NEt (1.2)
DBU (1,2)
pyridine (1,2)
K2CO3 (3.0)
K2CO3 (3.0)
K2CO3 (3.0)
K2CO3 (3.0)
K2CO3 (3.0)
K2CO3 (3.0)
Na2CO3 (3.0)
Cs2CO3 (3.0)
d
9
10
11
12
13
14
15
16
17
18
19
20
21
22
47 (19)a
77 (3)a
K2CO3 (5.0)
K2CO3 (3.0)
K2CO3 (5.0)
K2CO3 (5.0)
K2CO3 (5.0)
K2CO3 (5.0)
23 (15)a
21 (51)a
55 (18)a
54 (24)a
73 (4)a
NCS (3.0)
NBS (3.0)
NIS (3.0)
DIH (1.5)
a
Yield of p-chlorobenzaldehyde.
Based on these results, various bromoarenes, such as p-dibro-
mobenzene, p-bromo(trifluoromethyl)benzene, p-bromocyano-
benzene, 1,3,5-tribromobenzene, m-bromochlorobenzene, 2-
bromopyridine, and 2,6-dibromopyridine, could be converted into
the corresponding aromatic ethyl esters in good yields by the
treatment of aromatic bromides with n-BuLi at ꢀ78 ꢁC, followed by
the reaction with ethyl formate at ꢀ78 ꢁC, and subsequently with
molecular iodine, K2CO3, and ethanol at room temperature, as
shown in Table 2 (entries 2e6, 14, 15). On the other hand, when
bromobenzene,
p-bromotoluene,
p-bromoanisole,
4-
bromobiphenyl, 1-bromonaphthalene, and 2-bromonaphthalene
were used as the substrate, the yields of ethyl esters were low to
moderate (entries 7e13), and aromatic aldehydes and diary-
lmethanols were obtained, respectively. The reason for this may be
the instability of the HCO2Et-adducts derived from the reaction of
aryllithium and ethyl formate under the present conditions;
HCO2Et-adducts decomposed to aromatic aldehydes and lithium
ethoxide even if the reactions were carried out at low temperature,
and the unfavorable formation of hemiacetals from the formed
aromatic aldehydes and ethanol, especially for electron-rich aro-
matic aldehydes. Once the aromatic aldehydes were formed, they
smoothly reacted with aryllithium to generate diarylmethanols.
The same treatment of iodobenzene derivatives, such as p-chlor-
oiodobenzene, p-bromoiodobenzene, 1,4-diiodobenzene, and 3,5-
bis(trifluoromethyl)iodobenzene, with n-BuLi, followed by the re-
action with ethyl formate, and then with molecular iodine, K2CO3,
and ethanol, also provided the corresponding aromatic ethyl esters
in good to moderate yields, respectively (entries 16e19).
Scheme 1. Introduction of ester group with ethyl chloroformate.
In the absence of a base, the ester was obtained in moderate
yield (entry 16). Moreover, Na2CO3 showed moderate reactivity but
was less effective than K2CO3 (entry 14). Cs2CO3 showed good re-
activity; however, K2CO3 is much more affordable than Cs2CO3
(entry 15). Optimization studies indicated that the treatment of the
HCO2Et-adduct with molecular iodine (3.0 equiv), K2CO3
(5.0 equiv), and ethanol (3 mL) in the third reaction step gave the
ester in good yield (entry 17). Then, the reactivity of molecular
iodine was compared with those of other halogen oxidants, such as
N-chlorosuccinimide (NCS), N-bromosuccinimide (NBS), N-iodo-
succinimide (NIS), and 1,3-diiodo-5,5-dimethylhydantoin (DIH).
The absence of an oxidant and NCS did not work well, NBS and NIS
gave ethyl p-chlorobenzoate in moderate yields, respectively,
whereas DIH gave ethyl p-chlorobenzoate in good yield, although
DIH is expensive (entries 18e22).
Then, the scope for conversion of p-bromo(trifluoromethyl)
benzene into the corresponding esters by changing formate esters

S. Ushijima et al. / Tetrahedron 68 (2012) 4701e4709
4703
Table 2
One-pot conversion of aromatic halides into aromatic ethyl esters with ethyl formate
Entry
AreX
Time (h)
Yield (%)
1
2
3
4
5c
6
7
8
9
R0¼p-Cl
14
14
14
15
14
14
18
14
14
77
80
84
71
90
74
R0¼p-Br
R0¼p-CF3
R0¼p-CN
R0¼3,5-diBr
R0¼m-Cl
R0¼H
23 (16)a(32)b
12 (27)a(41)b
7 (52)a(21)b
R0¼p-Me
R0¼p-OMe
Scheme 2. Preparation of p-(trifluoromethyl)benzoate esters with p-bromo(tri-
fluoromethyl)benzene and formate esters.
10
18
18
18
38 (34)a(14)b
49 (17)a(14)b
32 (32)a
ethyl benzofuran-2-carboxylate in 99% yield, as shown in Table 3
(entry 1). Using the same procedure and conditions, benzothio-
phene, benzothiazole, N-methylimidazole, 1,3-difluorobenzene,
1,2,4,5-tetrafluorobenzene, and phenylacetylene could be con-
verted into the corresponding aromatic ethyl esters in good yields
(Table 3, entries 2e7). On the other hand, when 1,3-
dimethoxybenzene and 1,4-dimethoxybenzene were used, the
corresponding ethyl esters were not obtained (entries 8, 9). Instead,
the aldehydes, which were the products of the hydrolysis of the
HCO2Et-adduct, were obtained, together with the starting materials
derived from the hydrolysis of the formed aryllithiums. This is due
to the smooth decomposition of the HCO2Et-adduct to the corre-
sponding aldehyde at the second step, and the formation of stable
aryllithiums, chelated between the lithium cation and the o-
methoxy group, at the first step.
11d
12d
13d
14
18
14
14
45 (15)a(10)b
73
79
15
Then, the introduction of an ester group with DMF, instead of
ethyl formate, to aromatics for the preparation of methyl esters in
good yields was studied. n-BuLi was added dropwise into a solution
of p-bromoanisole in THF at ꢀ78 ꢁC and the obtained mixture was
stirred for 0.5 h at the same temperature. Thereafter, DMF
(1.1 equiv) was added at room temperature and the obtained
mixture was stirred at the same temperature. After 2 h, methanol
(3 mL) was added and the obtained mixture was stirred for 0.5 h at
room temperature. Then, molecular iodine (1.6 equiv) and K2CO3
(3.0 equiv) were added and the reaction mixture was stirred for
18 h at room temperature to give methyl p-methoxybenzoate in
51% yield, together with p-methoxybenzaldehyde (23%) and N,N-
dimethyl-p-methoxybenzamide (13%), as shown in Table 4 (entry
1). Based on the optimization study, it was found that THF solvent
must be removed before the third reaction step and 3.0 equiv of
molecular iodine must be added in the fourth reaction step to
produce methyl p-methoxybenzoate in good yield. Thus, after the
reaction of p-bromoanisole with n-BuLi and subsequently with
DMF, THF was removed. The residue was treated with methanol
(3 mL), and this was followed by the reaction with molecular iodine
(3.0 equiv) and K2CO3 for 22 h at room temperature to give methyl
p-methoxybenzoate in the best yield, as shown in Table 4 (entry 5).
On the other hand, when EtOH, i-PrOH, and t-BuOH were used
instead of methanol, the corresponding esters were obtained in low
yields (19%, 21%, and 0%) under the same conditions. When the
reactivity of molecular iodine was compared with those of NCS,
NBS, NIS, and DIH, NCS and NBS did not work at all, whereas NIS
16
17
18
19
R0¼p-Cl
16
16
16
16
57
68
R0¼p-Br
R0¼p-l
69 (10)e
55
R0¼3,5-diCF3
a
Yield of aromatic aldehyde.
Yield of diarylmethanol.
Et2O (9.0 mL) was used instead of THF.
EtOH (3.0 mL) was used at the third step after THF was removed.
Yield of iodobenzene.
b
c
d
e
and alcohols was studied. The treatment of p-bromo(tri-
fluoromethyl)benzene with n-BuLi, followed by the reaction with
methyl formate, 1-propyl formate, or 2-propyl formate, and sub-
sequently with molecular iodine, K2CO3, and methanol, 1-propanol,
or 2-propanol, generated methyl p-(trifluoromethyl)benzoate in
58% yield,1-propyl p-(trifluoromethyl)benzoate in 86% yield, and 2-
propyl p-(trifluoromethyl)benzoate in 60% yield, respectively, as
shown in Scheme 2. Thus, the esters were obtained in good yields
with ethyl formate and ethanol, and with 1-propyl formate and 1-
propanol. In contrast, the yields of esters with methyl formate and
2-propyl formate were moderate.
Then, n-BuLi was added dropwise into a solution of benzofuran
in THF at 0 ꢁC and the obtained mixture was stirred for 2 h at the
same temperature. Thereafter, ethyl formate was added at ꢀ78 ꢁC
and the obtained mixture was stirred at the same temperature.
After 3 h, molecular iodine, K2CO3, and ethanol were added and the
obtained mixture was stirred for 13 h at room temperature to give

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S. Ushijima et al. / Tetrahedron 68 (2012) 4701e4709
Table 3
Table 4
One-pot conversion of aromatics into aromatic ethyl esters with ethyl formate
Optimization for the reaction conditions with p-bromomethoxybenzenea
Entry ROH
Oxidant (x equiv) Time (h) Temp
Yield (%)
Entry
1
AreH
Time (h)
13
Yield (%)
1d
2
3
4
5
MeOH
I2 (1.6)
I2 (1.6)
I2 (1.6)
I2 (1.6)
I2 (3.0)
I2 (3.0)
I2 (3.0)
18
16
16
45
22
20
20
20
21
21
21
21
0
0
0
0
0
0
0
0
0
0
0
0
ꢁC/rt
ꢁC/rt
51 (23)b(13)c
MeOH
MeOH
MeOH
MeOH
EtOH
65 (10)b(6)c
ꢁC/60 ꢁC 68 (10)b(6)c
>99
ꢁC/rt
ꢁC/rt
ꢁC/rt
ꢁC/rt
ꢁC/rt
ꢁC/rt
ꢁC/rt
ꢁC/rt
ꢁC/rt
73 (8)c
82 (4)c
6
19 (55)b(8)c
21 (49)b(3)c
0 (51)b(28)c
0 (45)b(28)c
Trace (56)b
66 (14)b(5)c
81 (4)b(3)c
2
15
18
14
73
75
71
7
i-PrOH
8
t-BuOH I2 (3.0)
9
MeOH
MeOH
MeOH
MeOH
NCS (3.0)
3c
4
10
11
12
NBS (3.0)
NIS (3.0)
DIH (1.5)
a
Conditions: THF solvent was removed before the third-step reaction.
Yield of p-methoxybenzaldehyde.
Yield of N, N-dimcthyl-p-methoxybenzamide.
b
c
d
Conditions: THF was not removed before the third-step reaction.
5c,d
16
40
64 (21)a
trimethyl-1-benzoate was low (entry 7) and the product of the hy-
drolysis of the DMF-adduct, 2,4,6-trimethyl-1-benzaldehyde, was
obtained as the main product. This is due to the steric hindrance in
the reaction of the DMF-adduct with methanol at the third step.
Then, n-BuLi was added dropwise into a solution of 1,4-
dimethoxybenzene in THF at 0 ꢁC and the obtained mixture was
stirred for 2 h at the same temperature. Thereafter, DMF was added at
0 ꢁC and the obtained mixture was stirred at room temperature. After
2 h, THF was removed, MeOH was added to the residue, and then, the
obtained mixture was stirred for 0.5 h at room temperature. Then,
molecular iodine (3.0 equiv) and K2CO3 (3.0 equiv) were added and
the obtained mixture was stirred at room temperature to give methyl
2,5-dimethoxy-1-benzoate in 70% yield, as shown inTable 6 (entry 2).
Using the same procedure and conditions, anisole, 1,2-
dimethoxybenzene, 1,3-difluorobenzene, 2-methoxynaphthalene,
N-methylimidazole, benzofuran, and benzothiophene, could be con-
verted into the corresponding aromatic methyl esters in good to
moderate yields (entries 1, 3, 6e10). On the other hand, when 1,3-
dimethoxybenzene and 1,3,5-trimethoxybenzene were used, the
yields of methyl esters were low (entries 4, 5) and the aldehydes were
obtained as the main product of each reaction. This is due to the
smooth decomposition of the DMF-adducts to the corresponding
aromatic aldehydes at the third reaction step, and the unfavorable
formation of hemiacetals from the formed aromatic aldehydes and
methanol, especially for electron-rich aromatic aldehydes.
6c,d
72
7d,e
10
15
72
8
0 (48)a (26)b
9
14
7 (32)a (33)b
a
Yield of aromatic aldehyde.
Yield of starting compound.
b
c
The first-step reaction was carried out at ꢀ78 ꢁC for 1 h.
d
e
EtOH (3 mL) was used at the third-step reaction after THF was removed.
The second-step reaction was carried out at ꢀ78 ꢁC for 12 h.
and DIH gave the corresponding methyl esters in 66% and 81%
yields, respectively.
A plausible reaction mechanism is shown in Scheme 3. Aromatic
bromide or arene reacts with n-BuLi to form aryllithium (a). Aryl-
lithium (a) reacts with formate ester to form adduct (b), which
further reacts with ethanol to generate hemiacetal (c). Hemiacetal
(c) reacts with molecular iodine to give hemiacetal-hypoiodite (d).7
Once hemiacetal-hypoiodite (d) is formed, HI elimination
smoothly occurs in the presence of K2CO3 to provide aromatic ester.
When DMF is used instead of formate ester, aryllithium (a) reacts
with DMF to form adduct (b0), which further reacts with methanol
to generate hemiacetal (c0) through the formation of hemiaminal
(e) and aldehyde (f). Hemiacetal (c0) reacts with molecular iodine to
give hemiacetal-hypoiodite (d0). Once hemiacetal-hypoiodite (d0) is
formed, HI elimination smoothly occurs in the presence of K2CO3 to
provide aromatic methyl ester. On the other hand, hemiaminal (e)
may directly react with molecular iodine to form hemiaminal-
Based on these results, various aromatic bromides, such as bro-
mobenzene, p-bromotoluene, p-bromoanisole, m-bromotoluene,
m-bromoanisole, o-bromotoluene, p-bromochlorobenzene, and p-
dibromobenzene, could be transformed into the corresponding ar-
omatic methyl esters in good yields, respectively, by the treatment
with n-BuLi and then with DMF, followed by the reaction with
methanol, molecular iodine, and K2CO3 after the removal of THF
from the reaction mixture, as shown in Table 5 (entries 1e6, 8, 9).
Using the same procedure and conditions,1-bromonaphthalene,
2-bromonaphthalene, 4-bromobiphenyl, 2-bromothiophene, and 2-
bromopyridine were also converted into the corresponding aro-
matic methyl esters in good yields (entries 10e14). The formation of
a small amount of N,N-dimethyl aromatic amide as the by-product
was observed in each reaction. On the other hand, when 2,4,6-
trimethyl-1-bromobenzene was used, the yield of methyl 2,4,6-

S. Ushijima et al. / Tetrahedron 68 (2012) 4701e4709
4705
Table 5
One-pot conversion of aromatic bromides into aromatic methyl esters with DMF
Table 6
One-pot conversion of aromatics into aromatic mehtyl esters with DMF
Time (h)a
Yield (%)
Entry
AreH
Time (h)a
Yield (%)
Entry
AreBr
1
2
3
4
R¼2-OMe
41
41
41
41
41
18
53 (6)b
70 (5)b
55 (5)b
13 (63)b
1
2
3
4
5
6
7
8
9
R0¼H
21
21
22
20
20
20
22
16
16
71 (12)b
79 (10)b
82 (4)b
81 (12)b
86 (8)b
78 (7)b
4 (65)c
R0¼p-Me
R0¼p-OMe
R0¼m-Me
R0¼m-OMe
R0¼o-Me
R0¼2,4,6-triMe
R0¼p-Cl
R¼2,5-diOMe
R¼2,3-diOMe
R¼2,6-diOMe
R¼2,4,6-triOMe
R¼2,6-diF
5
0 (55)b(44)c
58 (10)d
6e
71 (15)b
71 (12)b
7
8
41
18
66 (5)b
R0¼p-Br
10
11
20
22
61 (7)b
79 (14)d
72 (6)b
9
18
18
64 (5)d
69 (5)b
10
70 (18)d
12
13
14
20
20
20
61 (13)b
63 (11)b
a
Conditions: solvent was removed before the third-step reaction.
Yield of aromatic aldehyde.
Yield of 1-iodo-2,4,6-trimethoxybenzene.
Yield of N,N-dimenthyl aromatic amide.
The first-step reaction was carried out at ꢀ78 ꢁC for 1 h.
b
c
d
e
a
Conditions: solvent was removed before the third-step reaction.
Yield of N,N-dimethyl aromatic amide.
Yield of aromatic aldehyde.
and therefore environmentally benign one-pot conversion of aro-
matic bromides and aromatics into the aromatic esters.
b
c
hypoiodite (g), and HI elimination may occur in the presence of
K2CO3 to provide N,N-dimethyl aromatic amide. Practically, in the
DMF system, the formation of N,N-dimethyl aromatic amide partly
occurs depending on the substrate.
4. Experimental section
4.1. General
1H NMR and 13C NMR spectra were obtained with JEOL-JNM-
ECX400, JEOL-JNM-ECS400, and JEOL-JNM-ECA500 spectrometers.
Chemical shifts were expressed in parts per million downfield from
3. Conclusion
TMS in
d units. Mass spectra were recorded on JMS-T100GCV, JMS-
Various aromatic bromides were treated with n-BuLi, and sub-
sequently with ethyl formate, followed by the reaction with ethanol
and molecular iodine in the presence of K2CO3 to provide the cor-
responding aromatic ethyl esters in good to moderate yields.
Moreover, aromatic bromides could be transformed into the cor-
responding aromatic methyl esters in good yields by the treatment
with n-BuLi and subsequently with DMF, followed by the reaction
with methanol, molecular iodine, and K2CO3. The latter method is
more effective than the former method, and both electron-deficient
and electron-rich aromatic bromides could be smoothly converted
into the corresponding aromatic methyl esters in good yields, ex-
cept for 2,6-disubstituted aromatic bromides. Some aromatics
could be also converted into the corresponding aromatic esters in
good yields by these two methods, and the latter method is more
effective than the former method again. The present reactions offer
a novel route for the transition-metal-free, carbon-monoxide-free,
HX110, and Thermo LTQ Orbitrap spectrometers. IR spectra were
measured with a JASCO FT/IR-4100 spectrometer. Melting points
were determined with Yamato Melting Point Apparatus Model MP-
21. Silica gel 60 (Kanto Kagaku Co.) was used for column chroma-
tography and Wakogel B-5F was used for preparative TLC.
4.2. Typical procedure for one-pot conversion of aromatic
bromides into aromatic ethyl esters with ethyl formate
n-BuLi (1.67 M solution in hexane,1.32 mL, 2.2 mmol) was added
dropwise into a solution of p-bromochlorobenzene (383 mg,
2.0 mmol) in THF (3 mL) at ꢀ78 ꢁC for 30 min. Then, ethyl formate
(1.6 mL, 20 mmol) was added to the mixture and the obtained
mixture was stirred at ꢀ78 ꢁC. After 3 h at the same temperature, I2
(1523 mg, 6 mmol), K2CO3 (1382 mg, 10 mmol) and EtOH (3 mL)

4706
S. Ushijima et al. / Tetrahedron 68 (2012) 4701e4709
(q, 2H, J¼7.2 Hz), 7.70 (d, 2H, J¼8.3 Hz), 8.16 (d, 2H, J¼8.9 Hz); 13C
NMR (125 MHz, CDCl3):
(q, JCeF¼3.6 Hz), 129.9, 133.7, 134.3 (q, JCeF¼32.4 Hz), 165.4.
d
14.9, 61.5, 123.6 (q, JCeF¼271.9 Hz), 125.3
4.2.4. Ethyl 4-cyano-1-benzoate. Mp 52e53 ꢁC (commercial, mp
52e54 ꢁC); IR (Nujol) 1716, 2228 cmꢀ1; 1H NMR (400 MHz, CDCl3):
d
1.42 (t, 3H, J¼7.2 Hz), 4.42 (q, 2H, J¼7.2 Hz), 7.75 (d, 2H, J¼8.6 Hz),
8.15 (d, 2H, J¼8.6 Hz); 13C NMR (100 MHz, CDCl3):
d 14.1, 61.7, 116.2,
117.9, 130.0, 132.1, 134.2, 164.8.
4.2.5. Ethyl 3,5-dibromo-1-benzoate. Mp 54e56 ꢁC (lit.8 mp
50e51 ꢁC); IR (Nujol) 1730 cmꢀ1; 1H NMR (500 MHz, CDCl3):
d 1.40
(t, 3H, J¼7.2 Hz), 4.38 (q, 2H, J¼7.2 Hz), 7.84 (s, 1H), 8.10 (s, 2H); 13C
NMR (125 MHz, CDCl3): d 14.2, 61.8, 122.9, 131.3, 133.6, 138.1, 164.0.
4.2.6. Ethyl 3-chloro-1-benzoate. Oil (commercial, oil); IR (neat)
1721 cmꢀ1; 1H NMR (400 MHz, CDCl3):
1.40 (t, 3H, J¼7.2 Hz), 4.38
d
(q, 2H, J¼7.2 Hz), 7.38 (t, 1H, J¼7.9 Hz), 7.52 (d, 1H, J¼7.9 Hz), 7.92 (d,
1H, J¼7.9 Hz), 8.01 (s, 1H); 13C NMR (125 MHz, CDCl3):
d 14.2, 61.3,
127.6, 129.5, 129.6, 132.2, 132.8, 134.4, 165.3.
4.2.7. Ethyl benzoate. Oil (commercial, oil); IR (neat) 1718 cmꢀ1; 1H
NMR (400 MHz, CDCl3):
d
1.38 (t, 3H, J¼7.2 Hz), 4.36 (q, 2H, J¼7.2 Hz),
7.37 (t, 2H, J¼7.7 Hz), 7.48 (t,1H, J¼7.3 Hz), 8.04 (d, 2H, J¼8.5 Hz); 13C
NMR (100 MHz, CDCl3): d 13.8, 60.3, 127.8, 129.0, 130.0, 132.2, 165.9.
4.2.8. Ethyl 4-methyl-1-benzoate. Oil (commercial, oil); IR (neat)
1717 cmꢀ1; 1H NMR (400 MHz, CDCl3):
1.37 (t, 3H, J¼7.2 Hz), 2.37
d
(s, 3H), 4.34 (q, 2H, J¼7.2 Hz), 7.20 (d, 2H, J¼7.0 Hz), 7.93 (d, 2H,
J¼7.3 Hz); 13C NMR (100 MHz, CDCl3):
d 14.2, 21.4, 60.6, 127.6, 128.8,
129.4, 143.2, 166.5.
4.2.9. Ethyl 4-phenyl-1-benzoate. Mp 45e46 ꢁC (lit.9 mp 46e48 ꢁC);
IR (Nujol) 1724 cmꢀ1 1H NMR (400 MHz, CDCl3):
1.39 (t, 3H,
;
d
J¼7.2 Hz), 4.38 (q, 2H, J¼7.2 Hz), 7.33e7.45 (m, 3H), 7.56e7.63 (m,
4H), 8.10 (d, 2H, J¼8.4 Hz); 13C NMR (100 MHz, CDCl3):
d 14.2, 60.8,
126.8, 127.1, 128.0, 128.8, 129.1, 129.9, 139.9, 145.3, 166.3.
4.2.10. Ethyl 1-naphthoate. Oil (commercial, oil); IR (neat)
1713 cmꢀ1; 1H NMR (400 MHz, CDCl3):
d
1.42 (t, 3H, J¼7.2 Hz), 4.45
(q, 2H, J¼7.2 Hz), 7.41e7.50 (m, 2H), 7.52 (t, 1H, J¼7.0 Hz), 7.82 (d,
1H, J¼8.2 Hz), 7.95 (d, 1H, J¼8.2 Hz), 8.16 (d, 1H, J¼7.3 Hz), 8.92 (d,
1H, J¼8.6 Hz); 13C NMR (100 MHz, CDCl3):
d 14.3, 60.9, 124.4, 125.7,
126.0, 127.3, 127.6, 128.4, 129.9, 131.2, 133.1, 133.7, 167.5.
Scheme 3. Plausible reaction mechanism.
4.2.11. Ethyl 2-naphthoate. Mp 33e34 ꢁC (lit.10 mp 35.5e36.2 ꢁC);
were added at ꢀ78 ꢁC and the mixture was stirred for 14 h at rt. The
reaction mixture was quenched with satd aq Na2SO3 (5 mL) and
was extracted with CHCl3 (3ꢂ20 mL). The organic layer was washed
with brine and dried over Na2SO4 to provide ethyl 4-
chlorobenzoate in 77% yield. If necessary, the product was puri-
fied by short column chromatography (SiO2:hexane:EtOAc¼9:1) to
give pure ethyl 4-chloro-1-benzoate as a colorless oil.
IR (Nujol) 1722 cmꢀ1 1H NMR (400 MHz, CDCl3):
; d 1.43 (t, 3H,
J¼7.2 Hz), 4.43 (q, 2H, J¼7.2 Hz), 7.49e7.58 (m, 2H), 7.85 (d, 2H,
J¼8.6 Hz), 7.93 (d, 1H, J¼7.9 Hz), 8.06 (dd, 1H, J¼8.6, 1.6 Hz), 8.60 (s,
1H); 13C NMR (100 MHz, CDCl3):
d 14.3, 61.0,125.2, 126.5, 127.7 (2C),
128.01, 128.07, 129.3, 130.9, 132.4, 135.4, 166.7.
4.2.12. Ethyl picolinate. Oil (commercial, oil); IR (neat) 1716 cmꢀ1
;
1H NMR (400 MHz, CDCl3):
d
1.45 (t, 3H, J¼7.2 Hz), 4.49 (q, 2H,
4.2.1. Ethyl 4-chloro-1-benzoate. Oil (commercial, oil); IR (neat)
J¼7.2 Hz), 7.48 (ddd, 1H, J¼7.7, 4.8,1.1 Hz), 7.85 (td, 1H, J¼7.7, 1.8 Hz),
1719 cmꢀ1; 1H NMR (500 MHz, CDCl3):
d
1.39 (t, 3H, J¼7.2 Hz), 4.37
8.14 (dt, 1H, J¼7.9, 1.1 Hz), 8.77 (ddd, 1H, J¼4.8, 1.8, 0.9 Hz); 13C NMR
(q, 2H, J¼7.2 Hz), 7.39 (d, 2H, J¼8.3 Hz), 7.97 (d, 2H, J¼8.9 Hz); 13C
(100 MHz, CDCl3): d 14.1, 61.8, 124.9, 126.7, 136.8, 148.1, 149.6, 165.0.
NMR (125 MHz, CDCl3): d 14.2, 61.1, 128.6, 128.9, 130.9, 139.1, 165.6.
4.2.13. Ethyl 6-bromopicolinate. Mp 41e42 ꢁC (commercial, mp
41 ꢁC); IR (Nujol) 1713 cmꢀ1 1H NMR (400 MHz, CDCl3)
1.33 (t,
4.2.2. Ethyl 4-bromo-1-benzoate. Oil (commercial, oil); IR (neat)
;
d
1719 cmꢀ1; 1H NMR (500 MHz, CDCl3):
d
1.39 (t, 3H, J¼7.2 Hz), 4.37
J¼7.2 Hz, 3H), 4.38 (q, 2H, J¼7.2 Hz), 7.26e7.70 (m, 2H), 7.96e8.03
(q, 2H, J¼7.2 Hz), 7.57 (d, 2H, J¼8.3 Hz), 7.90 (d, 2H, J¼8.3 Hz); 13C
(m, 1H); 13C NMR (100 MHz, CDCl3)
141.8, 148.7, 163.6.
d 14.0, 62.0, 123.8, 131.5, 139.1,
NMR (125 MHz, CDCl3): d 14.2, 61.2, 127.8, 129.3, 131.0, 131.6, 165.8.
4.2.3. Ethyl 4-(trifluoromethyl)-1-benzoate. Oil (lit.3g oil); IR (neat)
1725 cmꢀ1; 1H NMR (500 MHz, CDCl3):
1.42 (t, 3H, J¼7.2 Hz), 4.42
4.2.14. Ethyl 4-iodo-1-benzoate. Oil (commercial, oil); IR (neat)
1718 cmꢀ1; 1H NMR (400 MHz, CDCl3):
1.38 (t, 3H, J¼7.2 Hz), 4.36
d
d

S. Ushijima et al. / Tetrahedron 68 (2012) 4701e4709
4707
(q, 2H, J¼7.2 Hz), 7.71e7.80 (m, 4H); 13C NMR (125 MHz, CDCl3):
(q, 2H, J¼7.2 Hz), 7.19e7.23 (m, 1H); 13C NMR (125 MHz, CDCl3):
d
14.2, 61.1, 100.5, 129.8, 130.9, 137.5, 165.9.
d
13.9, 62.7, 108.4 (t, JCeF¼22.8 Hz), 113.9 (t, JCeF¼16.8 Hz), 144.3
(ddt, JCeF¼254.6, 14.3, 4.8 Hz), 145.9 (dtd JCeF¼248.1, 12.0, 4.8 Hz),
159.5; HRMS (ESI) [MþNa]þ, Calcd for C9H6O2F4Na¼245.0196,
observed¼245.0193.
4.2.15. Ethyl 3,5-bis(trifluoromethyl)-1-benzoate. Oil (lit.11 oil); IR
(neat) 1733 cmꢀ1 1H NMR (400 MHz, CDCl3):
; d 1.45 (t, 3H,
J¼7.2 Hz), 4.47 (q, 2H, J¼7.2 Hz), 8.06 (s, 1H), 8.50 (s, 2H); 13C NMR
(100 MHz, CDCl3):
JCeF¼3.3 Hz), 129.7, 132.1 (q, JCeF¼33.2 Hz), 132.7, 163.9.
d
14.2, 62.2, 122.9 (q, JCeF¼271.2 Hz), 126.2 (q,
4.2.25. Ethyl 3-phenylpropiolate. Oil (commercial. oil); IR (neat)
1708, 2211 cmꢀ1; 1H NMR (400 MHz, CDCl3):
d
1.35 (t, 3H, J¼7.2 Hz),
4.29 (q, 2H, J¼7.2 Hz), 7.33e7.47 (m, 3H), 7.58 (d, 2H, J¼8.3 Hz); 13C
4.2.16. Methyl 4-(trifluoromethyl)-1-benzoate. Oil (lit.12 oil); IR
NMR (100 MHz, CDCl3):
132.9, 154.0.
d 14.0, 62.0, 80.7, 86.0, 119.6, 128.5, 130.5,
(neat) 1741 cmꢀ1; 1H NMR (500 MHz, CDCl3):
d 3.96 (s, 3H), 7.71 (d,
2H, J¼8.6 Hz), 8.15 (d, 2H, J¼8.0 Hz); 13C NMR (125 MHz, CDCl3):
d
52.4, 123.6 (q, JCeF¼270.7 Hz), 125.3 (d, JCeF¼3.6 Hz), 129.9, 133.3,
4.3. Typical procedure for one-pot conversion of aromatic
bromides into aromatic methyl esters with DMF
134.3 (q, JCeF¼32.4 Hz), 165.8.
4.2.17. 10-Propyl 4-(trifluoromethyl)-1-benzoate. Oil; IR (neat)
n-BuLi (1.67 M solution in hexane, 1.3 mL, 2.2 mmol) was added
dropwise into a solution of p-bromoanisole (383 mg, 2.0 mmol) in
THF (3 mL) at ꢀ78 ꢁC for 30 min. Then, DMF (0.22 mL, 2.2 mmol)
was added to the mixture and the obtained mixture was stirred at
rt. After 2 h at the same temperature, THF was removed. Then,
MeOH (3 mL) was added to the residue and the mixture was stirred
at room temperature. After 30 min, I2 (1523 mg, 6 mmol) and K2CO3
(829 mg, 6 mmol) were added at 0 ꢁC and the obtained mixture was
stirred for 22 h at rt. The reaction mixture was quenched with satd
aq Na2SO3 (5 mL) and was extracted with CHCl3 (3ꢂ20 mL). The
organic layer was washed with brine and dried over Na2SO4 to
provide methyl 4-methoxy-1-benzoate in 82% yield. If necessary,
the product was purified by short column chromatography
(SiO2:hexane:EtOAc¼9:1) to give pure methyl 4-methoxybenzoate
as a colorless oil.
1726 cmꢀ1; 1H NMR (400 MHz, CDCl3):
d
1.04 (t, 3H, J¼7.2 Hz), 1.81
(sextet, 2H, J¼7.2 Hz), 4.32 (t, 2H, J¼6.7 Hz), 7.70 (d, 2H, J¼8.4 Hz),
8.16 (d, 2H, J¼8.2 Hz); 13C NMR (100 MHz, CDCl3):
d 10.4, 22.0, 67.1,
123.6 (q, JCeF¼272.8 Hz), 125.3 (q, JCeF¼3.8 Hz), 129.9, 133.7, 134.3
(q, JCeF¼32.4 Hz), 165.4; HRMS (ESI) [M]þ, Calcd for
C11H11O2F3¼232.0706, observed¼232.0697.
4.2.18. Isopropyl 4-(trifluoromethyl)-1-benzoate. Oil (lit.13 oil); IR
(neat) 1731 cmꢀ1 1H NMR (500 MHz, CDCl3):
; d 1.39 (d, 6H,
J¼6.3 Hz), 5.28 (septet, 1H, J¼6.3 Hz), 7.69 (d, 2H, J¼8.0 Hz), 8.15 (d,
2H, J¼8.0 Hz); 13C NMR (125 MHz, CDCl3):
d 21.8, 69.1, 123.7 (q,
JCeF¼272.3 Hz),125.3 (q, JCeF¼3.6 Hz),129.9,134.1 (q, JCeF¼32.4 Hz),
134.2, 164.8.
4.2.19. Ethyl benzofuran-2-carboxylate. Oil (lit.14 mp 30 ꢁC); IR
(neat) 1731 cmꢀ1
;
1H NMR (400 MHz, CDCl3):
d
1.43 (t, 3H,
4.3.1. Methyl benzoate. Oil (commercial, oil); IR (neat) 1722 cmꢀ1
;
J¼7.2 Hz), 4.44 (q, 2H, J¼7.2 Hz), 7.30 (t, 1H, J¼7.8 Hz), 7.44 (t, 1H,
1H NMR (400 MHz, CDCl3):
d
3.90 (s, 3H), 7.42 (t, 2H, J¼7.7 Hz), 7.54
J¼7.8 Hz), 7.52 (s, 1H), 7.59 (d, 1H, J¼8.0 Hz), 7.67 (d, 1H, J¼8.0 Hz);
(t, 1H, J¼7.3 Hz), 8.04 (d, 2H, J¼8.5 Hz); 13C NMR (100 MHz, CDCl3):
13C NMR (100 MHz, CDCl3):
d
14.3, 61.5, 112.3, 113.7, 122.7, 123.7,
d 52.0, 128.2, 129.5, 130.1, 132.8, 167.0.
126.9, 127.5, 145.7, 155.6, 159.5.
4.3.2. Methyl 4-methyl-1-benzoate. Mp 33e34 ꢁC (commercial, mp
4.2.20. Ethyl benzo[b]thiophene-2-cꢀa1rboxylate. Mp 34e35 ꢁC (lit.15
32 ꢁC); IR (Nujol) 1729 cmꢀ1; 1H NMR (400 MHz, CDCl3):
d 2.38 (s,
mp 36e38 ꢁC); IR (Nujol) 1715 cm
;
1H NMR (400 MHz, CDCl3):
3H), 3.88 (s, 3H), 7.21 (d, 2H, J¼8.0 Hz), 7.92 (d, 2H, J¼8.0 Hz); 13C
d
1.42 (t, 3H, J¼7.2 Hz), 4.41 (q, 2H, J¼7.2 Hz), 7.36e7.47 (m, 2H),
7.83e7.89 (m, 2H), 8.06 (s, 1H); 13C NMR (125 MHz, CDCl3):
14.2,
61.5, 122.7, 124.8, 125.4, 126.8, 130.3, 133.8, 138.6, 142.1, 162.7.
NMR (100 MHz, CDCl3): d 21.5, 51.8, 127.3, 129.0, 129.5, 143.4, 167.0.
d
4.3.3. Methyl 4-methoxy-1-benzoatꢀe.1 Mp 49e51 ꢁC (commercial,
mp 48e52 ꢁC); IR (Nujol) 1725 cm
;
1H NMR (400 MHz, CDCl3):
4.2.21. Ethyl benzo[d]thiazole-2-carboxylate. Mp 68e71 ꢁC (lit.16
mp 68e70 ꢁC); IR (Nujol) 1749 cmꢀ1 1H NMR (400 MHz, CDCl3):
d
3.85 (s, 3H), 3.88 (s, 3H), 6.91 (d, 2H, J¼8.8 Hz), 7.99 (d, 2H,
;
J¼9.1 Hz); 13C NMR (100 MHz, CDCl3):
d 51.8, 55.4, 113.6, 122.6,
d
1.49 (t, 3H, J¼7.2 Hz), 4.56 (q, 2H, J¼7.2 Hz), 7.52e7.61 (m, 2H),
131.5, 163.3, 166.8.
7.98 (d, 1H, J¼7.6 Hz), 8.25 (d, 1H, J¼7.7 Hz); 13C NMR (100 MHz,
CDCl3):
160.6.
d
14.3, 63.1, 122.0, 125.5, 127.0, 127.5, 136.8, 153.2, 158.5,
4.3.4. Methyl 3-methyl-1-benzoate. Oil (commercial, oil); IR (neat)
1723 cmꢀ1 1H NMR (500 MHz, CDCl3):
2.36 (s, 3H), 3.87 (s, 3H),
7.25e7.35 (m, 2H), 7.79e7.86 (m, 2H); 13C NMR (125 MHz, CDCl3):
d 21.1, 51.8, 126.5, 128.1, 130.0 (2C), 133.5, 137.9, 167.1.
;
d
4.2.22. Ethyl 1-methyl-1H-imidazole-2-carboxylate. Mp 44e46 ꢁC
(lit.17 mp 43e45 ꢁC); IR (Nujol) 1715 cmꢀ1 1H NMR (400 MHz,
;
CDCl3):
d
1.43 (t, 3H, J¼7.2 Hz), 4.02 (s, 3H), 4.41 (q, 2H, J¼7.2 Hz),
4.3.5. Methyl 3-methoxy-1-benzoate. Oil (commercial, oil); IR
(neat) 1721 cmꢀ1; 1H NMR (400 MHz, CDCl3):
3.84 (s, 3H), 3.91 (s,
7.05 (d, 1H, J¼1.3 Hz), 7.13 (d, 1H, J¼1.3 Hz); 13C NMR (100 MHz,
d
CDCl3):
d
14.0, 35.6, 61.1, 126.0, 129.1, 136.5, 159.0.
3H), 7.09 (d, 1H, J¼8.3 Hz), 7.33 (t, 1H, J¼7.9 Hz), 7.55 (s, 1H), 7.63 (d,
1H, J¼8.2 Hz); 13C NMR (100 MHz, CDCl3):
d 52.1, 55.3, 113.9, 119.9,
4.2.23. Ethyl 2,6-difluoro-1-benzoate. Oil; IR (neat) 1736 cmꢀ1
;
1H
121.9, 129.3, 131.4, 159.5, 166.9.
NMR (500 MHz, CDCl3):
d
1.39 (t, 3H, J¼7.2 Hz), 4.42 (q, 2H,
J¼7.2 Hz), 6.94 (t, 2H, J¼8.2 Hz), 7.37e7.43 (m, 1H); 13C NMR
4.3.6. Methyl 2-methyl-1-benzoate. Oil (commercial, oil); IR (neat)
(125 MHz, CDCl3):
d
14.0, 61.9, 111.3 (t, JCeF¼18.0 Hz), 118.2 (dd,
1722 cmꢀ1 1H NMR (400 MHz, CDCl3):
; d 2.60 (s, 3H), 3.88 (s, 3H),
JCeF¼21.0, 4.2 Hz), 132.4 (t, JCeF¼10.8 Hz), 160.5 (dd, JCeF¼254.0,
7.21e7.25 (m, 2H), 7.38 (t, 1H, J¼7.5 Hz), 7.90 (d, 1H, J¼8.2 Hz); 13C
6.0
Hz),
161.5;
HRMS
(ESI)
[MþNa]þ,
Calcd
for
NMR (100 MHz, CDCl3):
140.1, 168.0.
d 21.6, 51.7, 125.6, 129.5, 130.5, 131.6, 131.9,
C9H8O2F2Na¼209.0385, observed¼209.0384.
4.2.24. Ethyl
2,3,5,6-tetrafluoro-1-benzoate. Oil;
IR
(neat)
4.3.7. Methyl 4-chloro-1-benzoate. Mp 43 ꢁC (commercial, mp
42e44 ꢁC); IR (Nujol) 1732 cmꢀ1; 1H NMR (500 MHz, CDCl3):
3.91
1741 cmꢀ1; 1H NMR (500 MHz, CDCl3):
d
1.41 (t, 3H, J¼7.2 Hz), 4.46
d

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S. Ushijima et al. / Tetrahedron 68 (2012) 4701e4709
(s, 3H), 7.40 (d, 2H, J¼8.6 Hz), 7.96 (d, 2H, J¼8.9 Hz); 13C NMR
6.92e6.98 (m, 2H), 7.38e7.45 (m, 1H); 13C NMR (125 MHz, CDCl3):
(125 MHz, CDCl3):
d
52.2, 128.5, 128.6, 130.9, 139.3, 166.1.
d
52.6, 110.9 (t, JCeF¼17.9 Hz), 111.67 (dd, JCeF¼20.9, 4.2 Hz), 132.7 (t,
JCeF¼10.1 Hz), 160.6 (dd, JCeF¼255.2, 6.0 Hz), 161.9.
4.3.8. Methyl 4-bromo-1-benzoate. Mp 77e79 ꢁC (commercial, mp
77e81 ꢁC); IR (Nujol) 1734 cmꢀ1; 1H NMR (500 MHz, CDCl3):
d
3.91
4.3.19. Methyl 3-methoxy-2-naphthoate. Mp 48e49 ꢁC (commer-
(s, 3H), 7.57 (d, 2H, J¼8.6 Hz), 7.90 (d, 2H, J¼8.9 Hz); 13C NMR
cial, mp 48e51 ꢁC); IR (Nujol) 1732 cmꢀ1 1H NMR (500 MHz,
;
(125 MHz, CDCl3):
d
52.2, 128.0, 129.0, 131.1, 131.7, 166.3.
CDCl3):
7.48 (t, 1H, J¼7.6 Hz), 7.69 (d, 1H, J¼8.3 Hz), 7.78 (d, 1H, J¼8.3 Hz),
8.28 (s, 1H); 13C NMR (125 MHz, CDCl3):
52.1, 55.8, 106.6, 121.6,
d
3.93 (s, 3H), 3.95 (s, 3H), 7.16 (s, 1H), 7.34 (t, 1H, J¼7.6 Hz),
4.3.9. Methyl 1-naphthoate. Oil (commercial, oil); IR (neat)
1715 cmꢀ1; 1H NMR (400 MHz, CDCl3):
3.96 (s, 3H), 7.40e7.51 (m,
d
d
124.2, 126.3, 127.4, 128.3, 128.5, 135.6, 135.9, 155.5, 166.5.
2H), 7.58 (t, 1H, J¼7.0 Hz), 7.82 (d, 1H, J¼8.2 Hz), 7.95 (d, 1H,
J¼8.4 Hz), 8.15 (d, 1H, J¼7.3 Hz), 8.92 (d, 1H, J¼8.6 Hz); 13C NMR
4.3.20. Methyl 1-methyl-1H-imidazole-2-carboxylate. Oil (lit.20 oil);
(100 MHz, CDCl3):
d
52.0, 124.4, 125.7, 126.1, 126.9, 127.6, 128.4,
IR (neat) 1725 cmꢀ1; 1H NMR (400 MHz, CDCl3):
d 3.92 (s, 3H), 4.01
130.1, 131.2, 133.2, 133.7, 167.9.
(s, 3H), 7.07 (d, 1H, J¼1.3 Hz), 7.13 (d, 1H, J¼1.3 Hz); 13C NMR
(100 MHz, CDCl3):
d 35.3, 51.7, 126.0, 129.0, 136.1, 159.2.
4.3.10. Methyl 2-naphthoate. Mp 75e76 ꢁC (commercial, mp
75e77 ꢁC); IR (Nujol) 1730 cmꢀ1; 1H NMR (400 MHz, CDCl3):
d
3.98
4.3.21. Methyl benzofuran-2-carboxylate. Mp 53e54 ꢁC (lit.21 mp
53e55 ꢁC); IR (Nujol) 1731 cmꢀ1; 1H NMR (500 MHz, CDCl3):
3.98
(s, 3H), 7.50e7.61 (m, 2H), 7.87 (d, 2H, J¼8.6 Hz), 7.95 (d, 1H,
d
J¼8.2 Hz), 8.06 (dd, 1H, J¼8.6, 1.8 Hz), 8.61 (s, 1H); 13C NMR
(s, 3H), 7.30 (t, 1H, J¼7.2 Hz), 7.45 (t, 1H, J¼7.2 Hz), 7.53 (s, 1H), 7.59
(100 MHz, CDCl3):
d 52.2, 125.2, 126.6, 127.4, 127.7, 128.1, 128.2,
(d, 1H, J¼8.3 Hz), 7.68 (d, 1H, J¼8.0 Hz); 13C NMR (125 MHz, CDCl3):
129.3, 131.0, 132.5, 135.5, 167.2.
d 52.3, 112.3, 114.0, 122.8, 123.8, 126.9, 127.6, 145.3, 155.7, 160.0.
4.3.11. Methyl 4-phenyl-1-benzoate. Mp 110e112 ꢁC (lit.18 mp
4.3.22. Methyl benzo[b]thiophene-2-carboxylate. Mpꢀ170e71 ꢁC
112e114 ꢁC); IR (Nujol) 1703 cmꢀ1
;
1H NMR (400 MHz, CDCl3):
(commercial, mp 70e74 ꢁC); IR (Nujol) 1725 cm
;
1H NMR
d
3.93 (s, 3H), 7.38 (t, 1H, J¼7.4 Hz), 7.46 (t, 2H, J¼7.4 Hz), 7.59e7.67
(400 MHz, CDCl3): d 3.94 (s, 3H), 7.37e7.48 (m, 2H), 7.84e7.88 (m,
(m, 4H), 8.10 (d, 2H, J¼8.6 Hz); 13C NMR (100 MHz, CDCl3):
d
52.1,
2H), 8.06 (s, 1H); 13C NMR (100 MHz, CDCl3):
125.5, 126.9, 130.6, 133.3, 138.6, 142.2, 163.2.
d 52.5, 122.7, 124.9,
127.0, 127.2, 128.1, 128.9 (2C), 130.1, 140.0, 145.6, 167.0.
4.3.12. Methyl thiophene-2-carboxylate. Oil (commercial oil); IR
(neat) 1703 cmꢀ1 1H NMR (500 MHz, CDCl3):
3.89 (s, 3H), 7.10
References and notes
;
d
1. The Art of Drug Synthesis: (a) Johnson, D. S., Li, J. J., Eds. ; John Wiley and Sons.:
Hoboken, NJ, 2007; (b) Zapf, A.; Beller, M. Top. Catal. 2002, 19, 101; (c) Stetter, J.;
Lieb, F. Angew. Chem., Int. Ed. 2000, 39, 1724.
(dd, 1H, J¼5.0, 4.3 Hz), 7.55 (dd, 1H, J¼5.0, 1.2 Hz), 7.80 (dd, 1H,
J¼4.3, 1.2 Hz); 13C NMR (125 MHz, CDCl3):
d 52.1, 127.7, 132.3, 133.4,
133.6, 162.7.
2. Fischer ester synthesis: (a) Fischer, E.; Speier, A. Ber. Dtsch. Chem. Ges. 1895, 28,
3252; (b) Bew, S. P.; Hughs, D. L.; Sharma, S. V. J. Org. Chem. 2006, 71, 7881; (c)
Larock, R. C. Comprehensive Organic Transformations, 2nd ed.; VCH: New York,
NY, U.S., 1989, pp 881e958. Mitsunobu Reaction; (d) Mitsunobu, O. Synthesis
1981, 1; (e) Watterson, M. P.; Fleet, G. W. J. Tetrahedron Lett. 2003, 44, 5853; (f)
Favorskii, A. E. J. Prakt. Chem. 1895, 51, 533 1913, 88, 658; (g) Baeyer, A.;
Villiger, V. Chem. Ber. 1899, 32, 3625; (h) Pinner, A.; Klein, F. Chem. Ber. 1883,
16, 1643.
3. (a) Schoenberg, A.; Bartoletti, I.; Heck, R. F. J. Org. Chem. 1974, 39, 3318 recent
reviews; (b) Skoda-Foldes, R.; Koller, L. Curr. Org. Chem. 2002, 6, 1097; (c)
Barnard, C. F. J. Organometallics 2008, 27, 5402 recent papers; (d) Watson, D. A.;
Fan, X.; Buchwald, S. L. J. Org. Chem. 2008, 73, 7096; (e) Martinelli, J. R.; Watson,
D. A.; Freckmann, D. M. M.; Barder, T. E.; Buchwald, S. L. J. Org. Chem. 2008, 73,
7102; (f) Munday, R. H.; Martinelli, J. R.; Buchwald, S. L. J. Am. Chem. Soc. 2008,
130, 2754; (g) Shang, R.; Fu, Y.; Li, J.; Zhang, S.; Guo, Q.; Liu, L. J. Am. Chem. Soc.
2009, 131, 5738; (h) Wu, X.; Neumann, H.; Matthlas, B. ChemCatChem 2010, 2,
509; (i) Yang, W.; Han, W.; Zhang, W.; Shan, L.; Sun, J. Synlett 2011, 2253; (j) Xin,
Z.; Gogsig, T. M.; Lindhardt, A. T.; Skrydstrup, T. Org. Lett. 2012, 14, 284.
4. (a) Bratton, L. D.; Huh, H.; Bartsch, R. A. J. Heterocycl. Chem. 2000, 37, 2599; (b)
Amedio, J. C. J.; Lee, G. T.; Prasad, K.; Repic, O. Synth. Commun. 1995, 25, 2599;
(c) Li, H.; Balsells, J. Tetrahedron Lett. 2008, 49, 2034.
4.3.13. Methyl picolinate. Oil (commercial oil); IR (neat) 1703 cmꢀ1
1H NMR (500 MHz, CDCl3):
4.02 (s, 3H), 7.50 (ddd, 1H, J¼7.7, 4.7,
;
d
1.2 Hz), 7.86 (td, 1H, J¼7.7, 1.7 Hz), 8.15 (dt, 1H, J¼7.7, 1.2 Hz), 8.76
(ddd, 1H, J¼4.7, 1.7, 0.9 Hz); 13C NMR (125 MHz, CDCl3):
d 52.8,
125.0, 126.8, 136.9, 147.8, 149.7, 165.6.
4.3.14. Methyl 2-methoxy-1-benzoate. Oil (commercial, oil); IR
(neat) 1731 cmꢀ1; 1H NMR (500 MHz, CDCl3):
3.89 (s, 3H), 3.90 (s,
d
3H), 6.95e6.99 (m, 2H), 7.46 (t, 1H, J¼7.9 Hz), 7.79 (d, 1H, J¼8.0 Hz);
13C NMR (100 MHz, CDCl3):
133.4, 159.0, 166.6.
d 51.9, 55.9, 111.9, 119.9, 120.0, 131.6,
4.3.15. Methyl 2,5-dimethoxy-1-benzoate. Oil (lit.19 oil); IR (neat)
1732 cmꢀ1 1H NMR (500 MHz, CDCl3):
3.79 (s, 3H), 3.86 (s, 3H),
;
d
3.89 (s, 3H), 6.92 (d, 1H, J¼8.9 Hz), 7.02 (dd, 1H, J¼8.9, 3.2 Hz), 7.33
5. (a) Ushijima, S.; Togo, H. Synlett 2010, 1562; (b) Ushijima, S.; Moriyama, K.;
Togo, H. Tetrahedron 2011, 67, 958.
(d,1H, J¼3.2 Hz); 13C NMR (125 MHz, CDCl3):
d 52.0, 55.7, 56.7,113.7,
6. Reviews: (a) Togo, H.; Iida, S. Synlett 2006, 2159; (b) Togo, H. J. Synth. Org. Chem.
(Japanese) 2008, 66, 652 Papers; (c) Mori, N.; Togo, H. Synlett 2004, 880; (d)
Mori, N.; Togo, H. Synlett 2005, 1456; (e) Mori, N.; Togo, H. Tetrahedron 2005, 61,
5915; (f) Ishihara, M.; Togo, H. Synlett 2006, 227; (g) Iida, S.; Togo, H. Synlett
2006, 2633; (h) Ishihara, M.; Togo, H. Tetrahedron 2007, 63, 1474; (i) Iida, S.;
Togo, H. Tetrahedron 2007, 63, 8274; (j) Iida, S.; Togo, H. Synlett 2007, 407; (k)
Iida, S.; Togo, H. Synlett 2008, 1639; (l) Iida, S.; Ohmura, R.; Togo, H. Tetrahedron
2009, 65, 6257; (m) Ushujima, S.; Togo, H. Synlett 2010, 1067; (n) Ishii, G.;
Moriyama, K.; Togo, H. Tetrahedron Lett. 2011, 52, 2404; (o) Baba, H.; Moriyama,
K.; Togo, H. Tetrahedron Lett. 2011, 52, 4303; (p) Suzuki, Y.; Yoshino, T.;
Moriyama, K.; Togo, H. Tetrahedron 2011, 67, 3809; (q) Suzuki, Y.; Moriyama, K.;
Togo, H. Tetrahedron 2011, 67, 7956; (r) Ushijima, S.; Dohi, S.; Moriyama, K.;
Togo, H. Tetrahedron 2012, 68, 1346.
7. (a) Yamada, S.; Morizono, D.; Yamamoto, K. Tetrahedron Lett. 1992, 3, 4329; (b)
Kiran, Y. B.; Ikeda, R.; Sakai, N.; Konakahara, T. Synthesis 2010, 276.
8. Motrenko, T. I.; Sevbo, D. P.; Nekhoroshev, A. A.; Ginzberg, O. F. Z. Org. Khm.
1978, 14, 1669.
9. Chen, X.; Hou, Y.; Wang, H.; Cao, Y.; He, J. J. Phys. Chem. C 2008, 112, 8172.
10. Palmelund, A.; Myers, E. L.; Tai, L. R.; Tisserand, S.; Butts, C. P.; Aggarwal, V. K.
Chem. Commun. 2007, 4128.
115.9, 119.5, 120.4, 152.9, 153.4, 166.4.
4.3.16. Methyl 2,3-dimethoxy-1-benzoate. Mp 48e49 ꢁC (commer-
cial, mp 48e52 ꢁC); IR (Nujol) 1725 cmꢀ1 1H NMR (400 MHz,
;
CDCl3):
d 3.88 (s, 3H), 3.90 (s, 3H), 3.91 (s, 3H), 7.04e7.09 (m, 2H),
7.32 (d, 1H, J¼7.0 Hz); 13C NMR (100 MHz, CDCl3):
d 52.1, 56.0, 61.4,
115.7, 122.1, 123.7, 126.0, 149.0, 153.4, 166.7.
4.3.17. Methyl 2,6-dimethoxy-1-benzoate. Mp 86e88 ꢁC (commer-
cial, mp 87e90 ꢁC); IR (Nujol) 1732 cmꢀ1 1H NMR (500 MHz,
;
CDCl3):
d
3.80 (s, 6H), 3.89 (s, 3H), 6.54 (d, 2H, J¼8.6 Hz), 7.27 (t, 1H,
J¼8.4 Hz); 13C NMR (125 MHz, CDCl3):
d 52.3, 55.9, 103.8, 112.9,
131.0, 157.2, 167.0.
4.3.18. Methyl 2,6-difluoro-1-benzoate. Oil (commercial, oil); IR
(neat) 1725 cmꢀ1 1H NMR (500 MHz, CDCl3):
3.95 (s, 3H),
;
d
11. Al-Aseer, M. A. J. Org. Chem. 1985, 50, 2715.

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