A practical, chemoselective approach to O-methylation of carboxylic acids with dimethyl malonate

Article abstract of DOI:10.1016/j.tet.2015.10.024

A practical and chemoselective method is described for the O-methylation of carboxylic acids. Dimethyl malonate, a low toxic and commercially available compound was found to be an effective methylating reagent for a variety of carboxylic acids affording methyl ester products in good to high yields and with excellent chemoselectivity, without the use of strong bases as additives. A mechanism involving the utilization of potassium bromide is tentatively proposed.

Full text of DOI:10.1016/j.tet.2015.10.024

Tetrahedron xxx (2015) 1e6
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
A practical, chemoselective approach to O-methylation of carboxylic
acids with dimethyl malonate
,
b
,
b
a
a
b
Jincheng Mao a , Defu Liu , Yongming Li , Jinzhou Zhao , Guangwei Rong ,
*
Hong Yan b, Guoqi Zhang c
,
*
a State Key Laboratory of Oil and Gas Reservoir Geology and Exploitation, Southwest Petroleum University, Chengdu 610500, PR China
b Key Laboratory of Organic Synthesis of Jiangsu Province, College of Chemistry, Chemical Engineering and Materials Science, Soochow University,
Suzhou 215123, PR China
c Department of Sciences, John Jay College and The Graduate Center, The City University of New York, New York, NY 10019, USA
a r t i c l e i n f o
a b s t r a c t
Article history:
A practical and chemoselective method is described for the O-methylation of carboxylic acids. Dimethyl
malonate, a low toxic and commercially available compound was found to be an effective methylating
reagent for a variety of carboxylic acids affording methyl ester products in good to high yields and with
excellent chemoselectivity, without the use of strong bases as additives. A mechanism involving the
utilization of potassium bromide is tentatively proposed.
Received 2 September 2015
Received in revised form 7 October 2015
Accepted 8 October 2015
Available online xxx
Ó 2015 Elsevier Ltd. All rights reserved.
Keywords:
O-Methylation
Carboxylic acids
Dimethyl malonate
Chemoselective
Potassium bromide
1. Introduction
to be inactive to this reaction due to their disability in deproto-
nating the nucleophiles.12
Methylation is a crucial organic transformation in numerous
processes of chemical and biological synthesis and in industry.1 The
development of methodology for practical methylation of nucleo-
philic substrates involving important natural products has attrac-
ted intensive attention over the past decades,2e5 and some efficient
reagents for mild, clean methylation of various substrates were
introduced. Amongst them, however, several methylating reagents
such as methyl iodide,3 dimethyl sulfate,4 and diazomethane5 that
were commonly used suffer from not only high toxicity and poor
safety, but also low reactivity in the absence of extra strong alkalis
during the reaction (Scheme 1). In recent years, dimethyl carbonate
(DMC), an alternative to those toxic methylating agents has been
developed.6e18 DMC is a nontoxic, inexpensive, and ‘green’ meth-
ylating reagent, and has been extensively explored in the methyl-
ation of phenol7 or NH-containing heteroaromatic8 substrates.
However, strong bases including both inorganic9 and organic ba-
ses10 or acidic compounds11 were generally required to achieve
reasonable reaction rates, and weaker bases are usually considered
a) Previous work
O
CH3I, (CH3)2SO4
or CH2N2
O
O
O
O
O
CH3
CH3
R
O
O
R
O
R
OH
strong base
up to 165oC
b) Our work
O
O
O
O
KBr, DMF
130oC
CH3
H3C
CH3
R
O
O
R
OH
Scheme 1. O-methylation of carboxylic acids.
O-Methylation or the methyl esterification of carboxylic acids is
popularly used in many chemical processes including the synthesis
of natural products, medicines and polymers, and the protection of
functional groups.13 Except for the toxic methylating reagents de-
scribed above, the ‘green’ DMC has also been reported to promote
the O-methylation of a range of carboxylic acids.14 However, the
substrates were limited to only electron-rich carboxylic acids and
harsh reaction conditions (>150 ꢀC high temperature, autoclave
reactor and strong bases) were usually employed.15 Besides, the
* Corresponding authors. Fax: þ86 28 83033546; e-mail addresses: jcmao@suda.
edu.cn (J. Mao), guzhang@jjay.cuny.edu (G. Zhang).
http://dx.doi.org/10.1016/j.tet.2015.10.024
0040-4020/Ó 2015 Elsevier Ltd. All rights reserved.
Please cite this article in press as: Mao, J.; et al., Tetrahedron (2015), http://dx.doi.org/10.1016/j.tet.2015.10.024

2
J. Mao et al. / Tetrahedron xxx (2015) 1e6
chemoselective methylation of carboxylic acid substrates bearing
hydroxyl or amino groups is still a challenging issue for synthetic
chemists.16,17 Therefore, this methodology has not been considered
to be practical for a large-scale application in industry of synthetic
chemistry.18
We have been recently dedicated to developing new chemical
reactions for the modification of functionalized carboxylic acid
derivatives, in particular cinnamic acid.19 and have reported a cop-
per-catalyzed, tert-butyl hydroperoxide (TBHP)-mediated methyl
esterification of a broad range of substrates including benzylic al-
cohols, aldehydes and carboxylic acids.20 During the course of
searching new methylating reagents for the practical methyl es-
terification of carboxylic acids, we observed that dimethyl malo-
nate (DMM), a methyl ester analogue of DMC, enabled efficient O-
methylation of a broad scope of carboxylic acids with excellent
chemoselectivity under relatively milder reaction conditions
(Scheme 1).
Herein, we report for the first time on the use of DMM as a low
toxic, commercially available methylating reagent for the practical
O-methylation of carboxylic acids under neutral conditions. High
yields were achieved for a variety of aromatic or heteroaromatic
carboxylic acid substrates in the presence of potassium bromide at
130 ꢀC and excellent chemoselectivity was found for carboxylic
acids bearing phenol, amine or amide functional groups.
NaHCO3 was found to improve the yield of ester to 81% (entries
2e5, Table 1). Similar to DMC-mediated methylation, the added
bases might be also crucial in the present reaction, as no reaction
was detected when the reaction was performed in the absence of
a base (entry 6, Table 1). Further screening of the reaction condi-
tions, however, suggested that the inorganic base additives were
actually unnecessary for the DMM-directed reaction. Surprisingly,
when a neutral salt, potassium iodide (KI, 20 mol %) was used to
replace the inorganic bases, 3a was obtained in 88% isolated yield
after heating the reactants at 130 ꢀC for 12 h in DMF (entry 7, Table
1). In order to further improve the yield of 3a, other potassium or
sodium halides were introduced with a 20 mol % loading amount to
the reaction between cinnamic acid and DMM at 130 ꢀC, and the
resultant yields are all between 70e90% (entries 8e11, Table 1).
Slightly lowering the temperature to 120 ꢀC drastically decreases
the yield in the case using NaI as a promotor (56% vs 84%, entry 12).
Interestingly, increasing the loading of KBr from 20 mol % to 30 mol
% was confirmed to be crucial to complete the reaction, and at this
end a 96% yield was achieved (entry 13, Table 1). The solvent effect
was also screened and the results revealed that DMF acted as the
best solvent for this reaction (entries 14e17, Table 1). It was found
that NaI also promoted a complete conversion of cinnamic acid
even at 120 ꢀC, although a much higher loading (1.0 equiv) was
required (entry 18, Table 1).
With the optimized protocol in hand for the facile O-methyla-
tion of cinnamic acid, we were next interested to expand the sub-
strate scope by varying the substituents on the aromatic ring of
cinnamic acid. The related results are summarized in Table 2. It was
found that various cinnamic acids with electron-donating groups
were excellent candidates for the O-methylation reactions, gener-
ating the corresponding esters 3be3h exclusively in high yields,
although the reactions of cinnamic acids with electron-
withdrawing groups gave slightly lower yields (70%e84% for
2. Results and discussion
Initially, we chose cinnamic acid as a model compound to study
the O-methylation reaction by using DMM as a methylating re-
agent. It was pleasing to find that the reaction between cinnamic
acid and DMM proceeded in the presence of a traditional inorganic
base, Na2CO3 in N,N-dimethyl formide (DMF) at 130 ꢀC, affording
methyl cinnamate (3a) in 61% yield after 12 h (entry 1, Table 1). This
indicates that DMM could behave as a methylating reagent similar
to DMC that was previously investigated. Other inorganic bases
such as K2CO3, Cs2CO3, NaHCO3 and K2HPO4 also promoted the O-
methylation reactions of cinnamic acid with DMM, while only
Table 2
The scope of the O-methylationsa
Table 1
Optimization of O-methylation of cinnamic acid with DMMa
O
COOH
O
O
O
O
O
1a
2a
3a
Entry
Catalyst (equiv.)
Solvent
T (ꢀC)
Conv. (%)b
Yield (%)c
1
2
3
4
5
6
7
8
Na2CO3 (0.2)
K2CO3 (0.2)
Cs2CO3 (0.2)
K2HPO4 (0.2)
NaHCO3 (0.2)
d
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMAc
DMSO
Xylene
PhCl
130
130
130
130
130
130
130
130
130
130
130
120
130
130
130
130
130
130
68
59
66
32
88
<5
92
95
89
76
88
64
98
85
77
26
<5
>99
61
53
60
25
81
NR
88
90
86
70
84
56
96
82
73
22
trace
98
KI (0.2)
KBr (0.2)
KF (0.2)
9
10
11
12
13
14
15
16
17
18
NaCl (0.2)
NaI (0.2)
NaI (0.2)
KBr (0.3)
KBr (0.3)
KBr (0.3)
KBr (0.3)
KBr (0.3)
NaI (1.0)
DMF
a
Unless otherwise stated, all reactions were carried out with 1a (cinnamic acid:
0.3 mmol) and 2a (DMM: 1.8 mmol, 6.0 equiv) in the air, 12 h.
b
GC-yield.
Isolated yield.
c
Please cite this article in press as: Mao, J.; et al., Tetrahedron (2015), http://dx.doi.org/10.1016/j.tet.2015.10.024

J. Mao et al. / Tetrahedron xxx (2015) 1e6
3
COOH
3ie3k). In addition, the O-methylation reaction of (E)-3-(naph-
O
O
KBr (30 mol%)
thalen-1-yl)acrylic acid also resulted in the isolation of the desired
product 3l in 92% yield. The heterocyclic trans-3-(pyridin-3-yl)
acrylic and acid was tolerated under the standard conditions,
O
O
DMF/130 oC/12 h
4, 92%
Scheme 4. The decarboxylation of 3-(naphthalen-2-yl)propiolic acid with DMM.
affording 3m in 85% yield. It was also found that a-methylcinnamic
acid can be proceeded well with the methylation product 3n iso-
lated in 86% yield. Delightfully, except for the substrates with
a trans-configuration depicted above, cis-substrate is equally ef-
fective. Thus, the reaction of a bulky substrate with a cis-configu-
ration, (Z)-3-mesitylacrylic acid provided the corresponding ester
product 3o in a high yield (90%), with the retention of the cis-
configuration.
It is worth noting that the present methodology is readily scaled
up and represents a practical route to prepare methyl esters of
a class of carboxylic acids. For example, cinnamic acid in a gram
scale (1.482 g) was subjected to react with DMM under the opti-
mized conditions for 24 h (Scheme 2), fine white solid of 3a
(1.454 g, 90%) was then obtained after a facile purification pro-
cedure (by flash column chromatograph).
and phenol was selectively methylated on the carboxyl-O position,
resulting in the isolation of 3s as the only product in 80% yield
when the reaction was performed under standard conditions. 1H-
indole-2-carboxylic acid having an additional amine group was also
converted to the O-methylated product 3t selectively, remaining
the amine unreacted, although the yield (66%) dropped slightly.
Interestingly, an N-protected amino acid, N-benzoylglycine was
confirmed to be a good candidate for the selective methylation, and
the amide-containing ester product 3u was harvested in an excel-
lent yield (96%). The results presented here are remarkable, as se-
lective methylation of carboxylic acids was scarcely approached by
known methylation strategies in the literature.13e17
O
O
O
O
O
O
KBr (30 mol%)
O
O
O
OH
KBr (30 mol%)
DMF, 130 oC/24 h
O
O
O
OH
O
O
O
O
DMF/130 oC/12 h
1.482 g
3a, 1.454 g (90%)
OH
OH
3s, 80%
Scheme 2. 1-Gram scale synthesis of methyl cinnamate ester 3a.
O
O
O
O
KBr (30 mol%)
N
OH
DMF/130 oC/12 h
N
O
Except for cinnamic acids, other kind of aromatic carboxylic
acids could also be transformed to the corresponding methyl esters
in high yields as illustrated in Scheme 3. 4-Phenyl benzoic acid
worked well under standard conditions, giving the ester 3p in 91%
yield. Heterocyclic esters 3q could also be prepared in high yield by
the efficient methylation of 2-furoic acid using DMM. In addition,
terephthalic acid, a substrate containing two carboxylic acid groups
favored methylation of both carboxylic acid units in the presence of
excess amount of DMM and pure bis-methylated product 3r was
afforded in a good yield. However, this protocol was not applicable
for aromatic propiolic acids, and when 3-(naphthalen-2-yl)pro-
piolic acid were used as a substrate, an unexpected compound 4
resulting from the decarboxylation reaction was isolated as the only
product in 92% yield (Scheme 4).
H
H
3t, 66%
O
O
O
O
O
OH
KBr (30 mol%)
N
H
N
H
O
O
O
DMF/130 oC/12 h
O
3u, 96%
Scheme 5. Chemoselectivity test for DMM-mediated O-methylation.
Based on the previous reports on the DMC-mediated methyla-
tion and relevant mechanistic studies,16,18 and our own findings in
this work, we proposed a possible mechanism for the KBr-
promoted O-methylation of carboxylic acids with DMM (Scheme
6). Initially, the O-nucleophile of carboxylate resulting from the
equilibrium reaction between carboxylic acid 1 and KBr readily
attacks the methyl group of DMM, forming a key intermediate A
with the release of potassium methoxide. A then reacts with
methanol that was generated from the reaction of HBr and potas-
sium methoxide, both available from the previous steps, to produce
the final ester product 3 by a nucleophilic substitution under
heating condition.
O
O
OH
O
O
O
KBr (30 mol%)
O
O
DMF/130 oC/12 h
3p, 91%
O
O
O
O
O
KBr (30 mol%)
O
O
OH
O
O
DMF/130 oC/12 h
3q, 90%
RCOOH + KBr
K+RCOO- +H+Br-
O
O
1
O
O
O
KBr 30%
OH
O
O
O
O
O
O
O
O
HO
DMF/130 oC/12 h
K+RCOO-
O
O
MeOK
O
R
O
O
O
O
2
A
3r, 70%
MeOK + H+Br-
MeOH + KBr
Scheme 3. Reactions of aromatic carboxylic acids with DMM.
O
O
O
O
O
MeOH
The chemoselectivity for the DMM-mediated O-methylation of
carboxylic acids was next investigated. Several represented car-
boxylic acid substrates incorporating a second nucleophilic func-
tional group such as hydroxyl, amine or amide were tested and
encouraging results were obtained, which are shown in Scheme 5.
It was demonstrated that the substrate bearing both carboxylic acid
R
OMe
HO
O
R
O
O
3
A
Scheme 6. A proposed mechanism for DMM-mediated methylation.
Please cite this article in press as: Mao, J.; et al., Tetrahedron (2015), http://dx.doi.org/10.1016/j.tet.2015.10.024

4
J. Mao et al. / Tetrahedron xxx (2015) 1e6
3. Conclusions
3H), 3.00e2.90 (m, 1H), 1.28 (d, J¼7.2 Hz, 6H). 13C NMR (100 MHz,
CDCl3)
d
¼167.7, 151.6, 144.9, 132.0, 128.2, 127.0, 116.8, 51.7, 34.10,
In conclusion, in this work an efficient and practical method for
the O-methylation of carboxylic acids has been developed by uti-
lizing a new inexpensive and low toxic methylating reagent, di-
methyl malonate. The protocol was proved to tolerate to a broad
scope of substrates including cinnamic acids with electron-
withdrawing or electron-donating groups, aromatic or heterocy-
clic carboxylic acids, and other functionalized carboxylic acids.
Excellent chemoselectivity was achieved for carboxylic acids
bearing additional hydroxyl, amine or amide groups. This work
provides an alternative ‘greener’ approach to the selective O-
methylation of a variety of carboxylic acids.
23.8; MS (m/z) calcd for C13H17O2 205.1, found 205.1 (MþH)þ.
4.2.4. (E)-Methyl 3-(4-methoxyphenyl)acrylate (3d). White solid;
1H NMR (400 MHz, CDCl3)
d
¼7.66 (d, J¼16.0 Hz, 1H), 7.48 (d,
J¼8.8 Hz, 2H), 6.91 (d, J¼8.8 Hz, 2H), 6.32 (d, J¼16.0 Hz, 1H), 3.84 (s,
3H), 3.80 (s, 3H). 13C NMR (100 MHz, CDCl3)
d
¼167.8, 161.4, 144.5,
129.7, 127.1, 115.2, 114.3, 55.4, 51.6; MS (m/z) calcd for C11H13O3
193.1, found 193.1 (MþH)þ.
4.2.5. (E)-Methyl 3-(3,4-dimethoxyphenyl)acrylate (3e). White
solid; 1H NMR (400 MHz, CDCl3)
d
¼7.61 (d, J¼16.0 Hz, 1H),
7.09e7.07 (dd, J¼8.4, 2.0 Hz, 1H), 7.02 (d, J¼2.0 Hz, 1H), 6.84 (d,
J¼8.0 Hz, 1H), 6.29 (d, J¼16.0 Hz, 1H), 3.89 (s, 6H), 3.77 (s, 3H). 13
C
4. Experiment
NMR (100 MHz, CDCl3)
115.5, 111.0, 109.6, 55.9, 55.9, 51.6; MS (m/z) calcd for C12H15O4
223.1, found 223.1 (MþH)þ.
d
¼167.7, 151.1, 149.2, 144.8, 127.3, 122.6,
4.1. General information
All reactions were carried out under an air atmosphere condi-
tion. various carboxylic acids, bases and salts were purchased from
Aldrich, Acros or Alfa. Column chromatography was generally
performed on silica gel (100e200 mesh) and reactions were
monitored by thin layer chromatography (TLC) using UV light
(254 nm) to visualize the course of the reactions. The 1H (400 MHz)
and 13C NMR (100 MHz) data were recorded on Bruker 400 M
Digital NMR Spectrometer using CDCl3 as solvent. The chemical
4.2.6. (E)-Methyl 3-(3,4,5-trimethoxyphenyl)acrylate (3f). White
solid; 1H NMR (400 MHz, CDCl3)
d
¼7.60 (d, J¼16.0 Hz, 1H), 6.75 (s,
2H), 6.34 (d, J¼16.0 Hz,1H), 3.88 (s, 6H), 3.87 (s, 3H), 3.80 (s, 3H). 13
C
NMR (100 MHz, CDCl3)
d
¼167.4, 153.4, 144.8, 140.1, 129.9, 117.0,
105.2, 60.9, 56.1, 51.7; MS (m/z) calcd for C13H17O5 253.1, found
253.1 (MþH)þ.
4.2.7. (E)-Methyl 3-m-tolylacrylate (3g). Pale yellow liquid; 1H
shifts (d) are reported in parts per million and coupling constants (J)
in Hertz. 1H NMR spectra was recorded with tetramethylsilane
NMR (400 MHz, CDCl3)
2H), 7.31e7.27 (m,1H), 7.22 (d, J¼7.4 Hz,1H), 6.45 (d, J¼16.0 Hz,1H),
3.83 (s, 3H), 2.39 (s, 3H). 13C NMR (100 MHz, CDCl3)
d
7.69 (d, J¼16.0 Hz, 1H), 7.35 (d, J¼6.0 Hz,
(
d
¼0.00 ppm) as internal reference; 13C NMR spectra was recorded
d
¼167.5, 145.1,
with CDCl3
(d
¼77.500 ppm) as internal reference. All of ESI-MS
138.6,134.3,131.1,128.8,128.7,125.3,117.6, 51.7, 21.3; MS (m/z) calcd
were performed by the State-authorized Analytical Center in Soo-
chow University.
for C11H13O2 177.1, found 177.1 (MþH)þ.
4.2.8. (E)-Methyl 3-(4-acetoxyphenyl)acrylate (3h). White solid; 1H
4.2. General procedure for KBr-mediated methylation of car-
boxylic acid with dimethyl malonate
NMR (400 MHz, CDCl3)
1H), 7.57 (d, J¼8.4 Hz, 2H), 6.51 (d, J¼16.0 Hz, 1H), 3.92 (s, 3H), 3.81
(s, 3H). 13C NMR (100 MHz, CDCl3)
d¼8.04 (d, J¼8.4 Hz, 2H), 7.70 (d, J¼16.0 Hz,
d
¼167.0, 166.5, 143.5, 138.6,
To a Schlenk tube equipped with a magnetic stir bar were added
under air, carboxylic acid (0.3 mmol), dimethyl malonate
(1.8 mmol) and KBr (0.09 mmol) in DMF (2 mL). The resultant re-
action mixture was kept stirring at the required temperature for
12 h. After indicated reaction time, the mixture was cooled down to
room temperature. It was poured into ethyl acetate, then washed
with water, extracted with ethyl acetate, dried by anhydrous
Na2SO4, then filtered and evaporated under vacuum, the residue
was purified by flash column chromatography (petroleum ether or
petroleum ether/ethyl acetate) to afford the corresponding cou-
pling products with high purity.
131.4, 130.1, 127.9, 120.2, 52.3, 51.9; MS (m/z) calcd for C12H13O4
221.1, found 221.1 (MþH)þ.
4.2.9. (E)-Methyl 3-(4-chlorophenyl)acrylate (3i). White solid; 1H
NMR (400 MHz, CDCl3)
d
¼7.65 (d, J¼16.0 Hz,1H), 7.47e7.45 (m, 2H),
7.38e7.36 (m, 2H), 6.42 (d, J¼16.0 Hz, 1H), 3.82 (s, 3H). 13C NMR
(100 MHz, CDCl3)
d
¼167.2, 143.4, 136.2, 132.9, 129.2, 129.2, 118.4,
51.8; MS (m/z) calcd for C10H10ClO2 197.1, found 197.1 (MþH)þ.
4.2.10. (E)-Methyl 3-(4-(trifluoromethyl)phenyl)acrylate (3j). White
solid; 1H NMR (400 MHz, CDCl3)
d
¼7.72 (d, J¼16.0 Hz, 1H),
7.68e7.62 (m, 4H), 6.53 (d, J¼16.0 Hz, 1H), 3.84 (s, 3H). 13C NMR
4.2.1. Methyl cinnamate (3a). White solid; 1H NMR (400 MHz,
(100 MHz, CDCl3)
J¼32.0 Hz,1C), 128.2, 125.9 (q, 1C), 123.81(d, J¼272 Hz, 1C), 120.4,
d
¼166.8, 143.0, 137.7 (d, J¼1.2 Hz, 1C), 131.8 (d,
CDCl3)
d
¼7.72 (d, J¼16.0 Hz, 1H), 7.55e7.53 (m, 2H), 7.41e7.39 (m,
3H), 6.47 (d, J¼16.0 Hz, 1H), 3.83 (s, 3H). 13C NMR (100 MHz, CDCl3)
51.9; MS (m/z) calcd for C11H10F3O2 231.1, found 231.1 (MþH)þ.
d
¼167.4, 144.8, 134.3, 130.3, 128.9, 128.1, 117.8, 51.7; MS (m/z) calcd
for C10H11O2 163.1, found 163.1 (MþH)þ.
4.2.11. (E)-Methyl 3-(4-cyanophenyl)acrylate (3k). White solid; 1H
4.2.2. (E)-Methyl 3-p-tolylacrylate (3b). White solid; 1H NMR
NMR (400 MHz, CDCl3)
d
¼7.70e7.66 (m, 3H), 7.62 (d, J¼8.4 Hz, 2H),
6.53 (d, J¼16.0 Hz, 1H), 3.83 (s, 3H). 13C NMR (100 MHz, CDCl3)
(400 MHz, CDCl3)
7.19 (d, J¼8.0 Hz, 2H), 6.40 (d, J¼16.0 Hz, 1H), 3.80 (s, 3H), 2.37 (s,
3H). 13C NMR (100 MHz, CDCl3)
d
¼7.67 (d, J¼16.0 Hz, 1H), 7.42 (d, J¼8.0 Hz, 2H),
d
¼166.6, 142.4, 138.7, 132.7, 128.4, 121.4, 118.3, 113.4, 52.0; MS (m/z)
calcd for C11H10NO2 188.1, found 188.1 (MþH)þ.
d
¼167.6, 144.9, 140.7, 131.7, 129.6,
128.1, 116.7, 51.6, 21.5; MS (m/z) calcd for C11H13O2 177.1, found 177.1
(MþH)þ.
4.2.12. (E)-Methyl 3-(naphthalen-1-yl)acrylate (3l). Pale yellow
liquid; 1H NMR (400 MHz, CDCl3)
d
¼8.57 (d, J¼15.8 Hz, 1H), 8.22 (d,
J¼8.3,1H), 7.90 (t, J¼7.6 Hz, 2H), 7.77 (d, J¼7.2 Hz,1H), 7.62e7.48 (m,
4.2.3. (E)-Methyl 3-(4-isopropylphenyl)acrylate (3c). Pale yellow
3H), 6.57 (d, J¼15.8 Hz, 1H), 3.89 (s, 3H). 13C NMR (100 MHz, CDCl3)
liquid; 1H NMR (400 MHz, CDCl3)
J¼8.2 Hz, 2H), 7.27 (d, J¼8.2 Hz, 2H), 6.43 (d, J¼16.0 Hz, 1H), 3.82 (s,
d
¼7.71 (d, J¼16.0 Hz, 1H), 7.48 (d,
d¼167.3, 141.9, 133.7, 131.7, 131.4, 130.6, 128.8, 126.9, 126.3, 125.5,
Please cite this article in press as: Mao, J.; et al., Tetrahedron (2015), http://dx.doi.org/10.1016/j.tet.2015.10.024

J. Mao et al. / Tetrahedron xxx (2015) 1e6
5
125.0, 123.394, 120.5, 51.8; MS (m/z) calcd for C14H13O2 213.1, found
213.1 (MþH)þ.
127.1, 52.4, 41.7; MS (m/z) calcd for C10H12NO3 194.1, found 194.1
(MþH)þ.
4.2.13. (E)-Methyl 3-(pyridin-3-yl)acrylate (3m). Yellow solid; 1H
Acknowledgements
NMR (400 MHz, CDCl3)
d
¼8.71 (d, J¼2.0 Hz, 1H), 8.58e8.57 (dd,
J¼4.8 Hz, 1.6 Hz, 1H), 7.83e7.80 (m, 1H), 7.65 (d, J¼16.0 Hz, 1H),
The research is supported by Open Fund (PLN1409) of State Key
Laboratory of Oil and Gas Reservoir Geology and Exploitation
(Southwest Petroleum University), the Major Program of the Na-
tional Natural Science Foundation of China (51490653) and 973
Program (2013CB228004). We are grateful to the grants from the
Scientific Research Foundation for the Returned Overseas Chinese
Scholars, State Education Ministry and the Key Laboratory of Or-
ganic Synthesis of Jiangsu Province. GZ acknowledges the American
Chemical Society Petroleum Research Fund (#54247-UNI3) and the
PSC-CUNY award (#67312-0045) from the City University of New
York for support.
7.33e7.29 (m, 1H), 6.49 (d, J¼16.0 Hz, 1H), 3.80 (s, 3H). 13C NMR
(100 MHz, CDCl3)
d
¼166.8, 151.0, 149.7, 141.1, 134.3, 130.2, 123.8,
120.0, 51.9; MS (m/z) calcd for C9H10NO2 164.1, found 164.1 (MþH)þ.
4.2.14. (E)-Methyl 2-methyl-3-phenylacrylate (3n). White solid; 1H
NMR (400 MHz, CDCl3)
d
¼7.72 (d, J¼1.6 Hz, 1H), 7.42 (d, J¼4.4 Hz,
4H), 7.37e7.33 (m, 1H), 3.85 (s, 3H), 2.15 (d, J¼1.6 Hz, 3H). 13C NMR
(100 MHz, CDCl3)
d
¼169.2, 139.0, 135.9, 129.6, 128.4, 128.3, 52.1,
14.1; MS (m/z) calcd for C11H13O2 177.1, found 177.1 (MþH)þ.
4.2.15. (Z)-Methyl 3-mesitylacrylate (3o). White solid; 1H NMR
(400 MHz, CDCl3)
d
¼7.09 (d, J¼12.0 Hz, 1H), 6.90 (s, 2H), 6.18 (d,
J¼12.0 Hz, 1H), 3.64 (s, 3H), 2.32 (s, 3H), 2.20 (s, 6H). 13C NMR
Supplementary data
(100 MHz, CDCl3)
51.3, 21.1, 20.2; MS (m/z) calcd for C13H17O2 205.1, found 205.1
(MþH)þ.
d¼165.8, 144.6, 136.8, 134.5, 132.6, 127.9, 122.2,
Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.tet.2015.10.024.
4.2.16. Methyl biphenyl-4-carboxylate (3p). White solid; 1H NMR
References and notes
(400 MHz, CDCl3)
7.51e7.48 (m, 2H), 7.44e7.41 (m, 1H), 3.97 (s, 3H). 13C NMR
(100 MHz, CDCl3)
d¼8.15e8.14 (m, 2H), 7.70e7.65 (m, 4H),
1. (a) Crosignani, S.; White, P. D.; Linclau, B. Org. Lett. 2002, 4, 1035; (b) Otera, J.
Angew. Chem., Int. Ed. 2001, 40, 2044.
d
¼167.0, 145.7, 140.0, 130.1, 128.9, 128.9, 128.2,
2. (a) Fischer, E.; Speier, A. Chem. Ber. 1895, 28, 3252; (b) Larock, R. C. Wiley-VCH:
New York, 1999. (c) Heller, S. T.; Sarpong, R. Org. Lett. 2010, 12, 4572; (d)
Brohmer, M. C.; Mundinger, S. M.; Bannwarth, W. Angew. Chem., Int. Ed. 2011, 50,
6175; (e) Das, S.; Bobbink, F. D.; Dyson, P. J. Angew. Chem., Int. Ed. 2014, 53,
12876; (f) Turner, R. A.; Hauksson, N. E.; Gipe, J. H.; Lokey, R. S. Org. Lett. 2013,
15, 5012; (g) Xia, Q. S.; Liu, X. L.; Chen, W. Z. Org. Lett. 2013, 15, 3326; (h)
Laplante, C.; Hall, D. G. Org. Lett. 2001, 3, 1487.
3. (a) Ahmad, A. R.; Mehta, L. K.; Parrick, J. Tetrahedron 1995, 51, 12899; (b) Wang,
T.; Lui, A. S. Org. Lett. 1999, 1, 1835; (c) Abbotto, A.; Bradamante, S.; Facchetti, A.
J. Org. Chem. 1997, 62, 5755; (d) Tratrat, C.; Giorgi-Renault, S.; Husson, H.-P. J.
Org. Chem. 2000, 65, 6773.
127.3, 127.1, 52.2; MS (m/z) calcd for C14H13O2 213.1, found 213.1
(MþH)þ.
4.2.17. Methyl furan-2-carboxylate (3q). Colorless liquid; 1H NMR
(400 MHz, CDCl3)
d
¼7.57 (d, J¼0.8 Hz, 1H), 7.18 (d, J¼3.6 Hz, 1H),
6.51e6.50 (dd, J¼3.6 Hz,1.8 Hz,1H), 3.89 (s, 3H). 13C NMR (100 MHz,
CDCl3)
d
¼158.7, 145.8, 144.1, 117.5, 111.4, 51.4; MS (m/z) calcd for
C6H7O3 127.1, found 127.1 (MþH)þ.
4. (a) Merz, A. Angew. Chem., Int. Ed. Engl. 1973, 12, 846; (b) Basak, A.; Nayak, M. K.;
Chakraborti, A. K. Tetrahedron Lett. 1998, 39, 4883; (c) Voskresensky, S.; Ma-
kosza, M. Synth. Commun. 2000, 30, 3523; (d) Chakraborti, A. K.; Basak, A.;
Grover, V. J. Org. Chem. 1999, 64, 8014.
4.2.18. Methyl 1H-indole-2-carboxylate (3t). White solid; 1H NMR
(400 MHz, CDCl3)
(dd, J¼8.3 Hz, 0.7 Hz, 1H), 7.38e7.34 (m, 1H), 7.27e7.26 (m, 1H),
7.19e7.17 (m, 1H), 3.99 (s, 3H). 13C NMR (100 MHz, CDCl3)
d¼9.12 (s, 1H), 7.73 (d, J¼8.0 Hz, 1H), 7.47e7.45
5. Pizey, J. S. Horwood: New York, 1974, 2, 65.
6. (a) Mauri, M. M.; Romano, U.; Rivetti, F. Q. Ing. Chim. Ital. 1985, 21, 6; (b) Shaikh,
A.-A. G.; Sivaram, S. Chem. Rev. 1996, 96, 951; (c) Selva, M.; Perosa, A. Green
Chem. 2008, 10, 457.
7. (a) Lissel, M.; Schmidt, S.; Neumann, B. Synthesis 1986, 382; (b) Bomben, A.;
Selva, M.; Tundo, P.; Valli, L. Ind. Eng. Chem. Res. 1999, 38, 2075; (c) Tundo, P.;
Trotta, F.; Moraglio, G.; Ligorati, F. Ind. Eng. Chem. Res. 1988, 27, 1565; (d) Barcelo,
G.; Grenouillat, D.; Senet, J. P.; Sennyey, G. Tetrahedron 1991, 46, 1839; (e) Selva,
M.; Trotta, F.; Tundo, P. J. Chem. Soc. 1992, 519.
d
¼162.6,
136.9, 127.5, 127.1, 125.5, 122.7, 120.9, 111.9, 108.8, 52.1; MS (m/z)
calcd for C10H10NO2 176.1, found 176.1 (MþH)þ.
4.2.19. 2-Ethynylnaphthalene (4). White solid; 1H NMR (400 MHz,
CDCl3)
d
¼8.07 (s, 1H), 7.86e7.81 (m, 3H), 7.58e7.51 (m, 3H), 3.19 (s,
1H). 13C NMR (100 MHz, CDCl3)
d
¼133.0, 132.8, 132.3, 128.6, 128.1,
8. (a) Selva, M.; Bomben, A.; Tundo, P. J. Chem. Soc., Perkin Trans. 1 1997, 1041; (b)
Selva, M.; Tundo, P.; Perosa, A. J. Org. Chem. 2001, 66, 677; (c) Shieh, W.-C.; Dell,
S.; Bach, A.; Blacklock, T. J. J. Org. Chem. 2003, 68, 1954.
127.8127.8, 126.9, 126.6, 119.4, 84.0, 77.5; MS (m/z) calcd for C12H9
153.1, found 153.1 (MþH)þ.
9. (a) Lee, Y.; Shimizu, I. Synlett 1998, 1063; (b) Tundo, P.; Rossi, L.; Loris, A. J. Org.
Chem. 2005, 70, 2219; (c) Rajabi, F.; Saidi, M. R. Synth. Commun. 2004, 34, 4179;
(d) Ouk, S.; Thiebaud, S.; Borredon, E.; Legars, P.; Lecomte, L. Tetrahedron Lett.
2002, 43, 2661; (e) Selva, M.; Tundo, P.; Perosa, A. J. Org. Chem. 2003, 68, 7374.
10. (a) Shieh, W.-C.; Lozanov, M.; Loo, M.; Repic, O.; Blacklock, T. J. Tetrahedron Lett.
2003, 44, 4563; (b) Tilstam, U. Org. Process Res. Dev. 2012, 16, 1974; (c) Laurila,
M. L.; Magnus, N. A.; Staszak, M. A. Org. Process Res. Dev. 2009, 13, 1199.
11. (a) Devulapelli, V. G.; Weng, H. S. Catal. Commun. 2009, 10, 1711; (b) Kirumakki,
S. R.; Nagaraju, N.; Narayanan, S. Appl. Catal. A 2002, 226, 175; (c) Kirumakki, S.
R.; Nagaraju, N.; Chary, K. V. R.; Narayanan, S. Appl. Catal. A 2003, 248, 161.
12. Glasnov, T. N.; Holbrey, J. D.; Kappe, C. O.; Seddon, K. R.; Yan, T. Green Chem.
2012, 14, 3071.
13. (a) Giordanengo, R.; Viel, S.; Hidalgo, M.; Allard-Breton, B.; Thevand, A.; Charles,
L. Rapid Commun. Mass. Spectrom. 2010, 24, 1941; (b) Otera, J. Wiley-VCH:
Weinheim, 2003, 249. (c) Rajapaksa, N. S.; McGowan, M. A.; Rienzo, M.; Ja-
cobsen, E. N. Org. Lett. 2013, 15, 706; (d) Schrader, T. O.; Johnson, B. R.; Lopez, L.;
Kasem, M.; Gharbaoui, T.; Sengupta, D.; Buzard, D.; Basmadjian, C.; Jones, R. M.
Org. Lett. 2012, 14, 6306.
4.2.20. Dimethyl terephthalate (3r). White solid; 1H NMR
(400 MHz, CDCl3)
(100 MHz, CDCl3)
C
d
¼8.10 (d, J¼0.4 Hz, 4H), 3.95 (s, 6H). 13C NMR
d
¼166.3, 133.9, 129.6, 52.4; MS (m/z) calcd for
10H11O4 195.1, found 195.1 (MþH)þ.
4.2.21. (E)-Methyl 3-(3-hydroxyphenyl)acrylate (3s). White solid;
1H NMR (400 MHz, CDCl3)
¼7.67 (d, J¼16.0 Hz, 1H), 7.27 (t,
d
J¼7.5 Hz, 1H), 7.10e7.06 (m, 2H), 6.95e6.92 (m, 1H), 6.43 (d,
J¼16.0 Hz, 1H), 3.84 (s, 3H). 13C NMR (100 MHz, CDCl3)
¼168.1,
d
156.4, 145.3, 135.7, 130.1, 120.7, 117.8, 117.8, 114.7, 52.0; MS (m/z)
calcd for C10H11O3 179.1, found 1791 (MþH)þ.
4.2.22. Methyl-2-benzamidoacetate (3u). Pale yellow liquid; 1H
ꢀ
14. (a) Shieh, W.-C.; Dell, S.; Repic, O. J. Org. Chem. 2002, 67, 2188; (b) Carafa, M.;
Mesto, E.; Quaranta, E. Eur. J. Org. Chem. 2011, 2458; (c) Shieh, W.-C.; Dell, S.;
NMR (400 MHz, CDCl3)
7.44e7.40 (m, 2H), 6.98 (s, 1H), 4.23e4.22 (m, 2H), 3.77 (d, J¼1.4 Hz,
3H). 13C NMR (100 MHz, CDCl3)
¼170.6, 167.6, 133.6, 131.8, 128.6,
d¼7.83e7.80 (m, 2H), 7.52e7.48 (m, 1H),
ꢀ
Repic, O. Org. Lett. 2001, 3, 4279.
ꢀ
15. (a) Shieh, W.-C.; Dell, S.; Repic, O. Tetrahedron Lett. 2002, 43, 5607; (b) Chau, K.
d
D. N.; Duus, F.; Le, T. N. Green Chem. Lett. Rev. 2013, 6, 89; (c) Caretto, A.; Perosa,
Please cite this article in press as: Mao, J.; et al., Tetrahedron (2015), http://dx.doi.org/10.1016/j.tet.2015.10.024

6
J. Mao et al. / Tetrahedron xxx (2015) 1e6
A. ACS Sustain. Chem. Eng. 2013, 1, 989; (d) Guerrero, L. R.; Rivero, I. R. ARKIVOC
2008, 11, 295; (e) Gharat, N.; Rathod, V. K. J. Mol. Catal. B 2013, 88, 36.
16. (a) Dhakshinamoorthy, A.; Sharmila, A.; Pitchumani, K. Chem.dEur. J. 2010, 16,
1128; (b) Selva, M.; Tundo, P. J. Org. Chem. 2006, 71, 1464.
17. (a) Su, X.; Li, J.; Xiao, F.; Wei, W.; Sun, Y. Ind. Eng. Chem. Res. 2009, 43, 3685; (b)
Selva, M.; Tundo, P. Tetrahedron Lett. 2003, 44, 8139.
19. (a) Yang, H.-L.; Sun, P.; Zhu, Y.; Yan, H.; Mao, J.-C. Chem. Commun. 2012, 7847;
(b) Yang, H.-L.; Yan, H.; Sun, P.; Zhu, Y.; Mao, J.-C. Green Chem. 2013, 15, 976; (c)
Yan, H.; Lu, L.-H.; Rong, G.-W.; Liu, D.-F.; Mao, J.-C. J. Org. Chem. 2014, 79, 7103;
(d) Rong, G.-W.; Liu, D.-F.; Lu, L.-H.; Yan, H.; Mao, J.-C. Tetrahedron 2014, 70,
5033.
20. Zhu, Y.; Yan, H.; Lu, L.-H.; Liu, D.-F.; Mao, J.-C. J. Org. Chem. 2013, 78, 9898.
18. Ji, Y.; Sweeney, J.; Zoglio, J.; Gorin, D. J. J. Org. Chem. 2013, 78, 11606.
Please cite this article in press as: Mao, J.; et al., Tetrahedron (2015), http://dx.doi.org/10.1016/j.tet.2015.10.024