Enol Ester Intermediate Induced Metal-Free Oxidative Coupling of Carboxylic Acids and Arylboronic Acids

Article abstract of DOI:10.1002/ejoc.201900137

A facile, efficient and environmentally friendly methodology for the preparation of phenolic esters is realized via metal-free coupling of carboxylic acids and arylboronic acids. This sequential one pot reaction, employing methyl propiolate as an activating reagent, proceeds through the formation of enol ester intermediate, followed by a nucleophilic attack on the C-O bond under the oxidation of hydrogen peroxide. These studies display that enol esters, despite previously being overlooked as synthetic intermediates, would be the valuable building blocks for developing carbon–carbon and carbon–heteroatom bond-forming reactions.

Full text of DOI:10.1002/ejoc.201900137

DOI: 10.1002/ejoc.201900137
Full Paper
EsterificationAbstract
Enol Ester Intermediate Induced Metal-Free Oxidative Coupling
of Carboxylic Acids and Arylboronic Acids
Xianjun Xu,[a] Huangdi Feng,*[a] Huiqiong Li,[a] and Liliang Huang[a]
Abstract: A facile, efficient and environmentally friendly meth- the C-O bond under the oxidation of hydrogen peroxide. These
odology for the preparation of phenolic esters is realized via studies display that enol esters, despite previously being over-
metal-free coupling of carboxylic acids and arylboronic acids. looked as synthetic intermediates, would be the valuable build-
This sequential one pot reaction, employing methyl propiolate ing blocks for developing carbon–carbon and carbon–hetero-
as an activating reagent, proceeds through the formation of atom bond-forming reactions.
enol ester intermediate, followed by a nucleophilic attack on
Introduction
copper catalysts in the oxidative coupling of carboxylic acids
with boronic acids, known as the Chan-Lam reaction, has pro-
Esters are ubiquitous structural elements of natural products, vided an attractive way to access ester-containing products
pharmaceuticals, agrochemicals, polymers, biological systems, (Scheme 1a).[11] In stark contrast to the classical approaches
and also serve as a versatile building block for further function- for the construction of ketones by palladium-catalyzed Suzuki–
alization in the design of valuable compounds.[1] Although a Miyaura reaction of carboxylic acid derivatives with boronic
series of approaches, including direct transformation of aerobic acids (Scheme 1b),[12] the group of Long disclosed an oxidative
oxidative coupling of aldehydes[2] or alcohols,[3] carbonylative coupling of carboxylic anhydrides with arylboronic acids cata-
coupling[4] and so on,[5] have been documented to generate lyzed by palladium, allowing the synthesis of esters
esters, decades of research have evolved condensation of acyl (Scheme 1c).[13] Nevertheless, these strategies are enabled by
transfer agents with alcohols or phenols into a commonly used transition metal catalysis.
method for their synthesis.[6] Recently, facile direct esterification
With the aforementioned advances in mind, we sought to
of carboxylic acids, representing a largely untapped branch of provide a benign and straightforward approach for converting
ester bond formation, has received intense attention.[7] Among carboxylic acids into the corresponding esters in a transition-
the reactions, significant contributions by Olofsson,[8] Zhang[9] metal-free transformation. Impressively, a recent class of reac-
and others[10] have established the cross coupling of carboxylic tions involving the use of acetylene derivatives as the activating
acids with diaryliodonium salts. Additionally, utilization of the reagents in the direct amidation of carboxylic acids have been
Scheme 1. Cross-coupling of carboxylate derivatives with boronic acids.
developed.[14] Expanding upon this theme, our laboratory intro-
duced a conceptually simpler protocol that combines carboxylic
acids with yanoates for the formation of C–N, C–O and C–S
bonds via the generation of enol ester as a highly reactive elec-
trophile.[15] Inspired by a number of hydroxylation of aryl-
boronic acids studies,[16] we herein wish to trap the enol ester
intermediate through an aerobic oxidative coupling reactivity
[a] College of Chemistry and Chemical Engineering,
Shanghai University of Engineering Science,
333 Longteng Road, Shanghai, 201620, China
E-mail: hdfeng@sues.edu.cn
http://www.escience.cn/people/PC-FENG/index.html
Supporting information and ORCID(s) from the author(s) for this article are
available on the WWW under https://doi.org/10.1002/ejoc.201900137.
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with boronic acids (Scheme 1d). This new transition-metal-free
With the established reaction parameters in hand, the scope
approach, avoiding the use of potentially toxic metal-based of carboxylic acids was then studied (Table 2). Benzoic acids
catalysts, delivers an advance that can produce highly function-
alized ester molecules under very mild reaction conditions.
bearing electron-donating (methyl, methoxyl at meta- and
para-position) and electron-withdrawing (fluoro, chloro at
ortho-, meta- and para-position) substituents on the phenyl unit
were suitable coupling partners for this sequential transforma-
tion, providing the corresponding products in good yields (4ba-
4ia). However, no corresponding products 4ja and 4ka were
detected when the reaction of a benzoic acid derivative with a
stronger electron-withdrawing group such as 4-cyanobenzoic
acid and 4-nitrobenzoic acid was carried out. It was worth men-
tioning that the electron-rich benzoic acids generally gave
higher yield than electron-poor substrates. Other aromatic ac-
ids, including 2-naphthoic acid and heterocyclic aromatic acids
were also able to deliver the desired esters 4la-4oa with the
yields of 77 %, 82 %, 93 % and 73 %, respectively. In addition,
cinnamic acid also showed good reactivity in the construction
of product 4pa. Inert aliphatic carboxylic acids such as 2-
phenylacetic acid and cyclohexanecarboxylic acid were unsuita-
ble substrates for the reaction.
Results and Discussion
The investigation of this esterification cascade was initiated by
the treatment of phenylboronic acid 3a with active α-acyl enol
ester 2a, which could be prepared from benzoic acid 1a and
methyl propiolate in the presence of triethylamine in CH3CN at
60°C. Remarkably, the reaction was conveniently performed at
room temperature, yielding 82 % of the isolated product 4aa in
the presence of hydrogen peroxide (Table 1, entry 1). A thor-
ough evaluation of the oxidants indicated that hydrogen per-
oxide was the optimal oxidation reagent. The commonly used
oxidants, m-PCBA and TBHP, were found to be effective on the
reaction but only gave the desired ester with 30 % yield and
69 % yield, respectively (entries 2 and 3). Whereas, the interme-
diate 2a was remained when using other oxidants such as DTBP,
DDQ and O2 (entries 4–6). Different solvents on this reaction
were futher screened. Among the solvents studied, chloroform,
1,2-dichloroethane (DCE), toluene, and 1,4-dixoane provided a
sharply decreased yield of 13 %-38 % (entries 7–10). Switching
the solvent into tetrahydrofuran resulted in a moderate yield of
62 % (entry 11). Further, a subsequent testing of the amount of
oxidant and phenylboronic acid was undertaken, and the yield
of target product was improved to 88 % when 0.8 equiv. of
starting boronic acid 3a was employed in combination with
1.2 equiv. of oxidant hydrogen peroxide (entries 12–14). In the
absence of activating reagent methyl propiolate, none of the
desired product was detected (entry 15). It implied that the
enol ester species 2a played a key role in this transformation.
In the next step, the coupling of benzoic acid 1a with differ-
ent boronic acids was examined under the standard conditions,
and satisfactorily target esters could be produced smoothly
with good results (Table 3). A diverse range arylboronic acids
with various functional groups, including electron-rich and elec-
tron-poor groups, was well tolerated and could finished the cor-
responding products 4ab-4ak in moderate to good yields. In
these cases, the sterically hindrance of the ortho substitution in
the arylboronic acid had a large influence on the reaction rate.
Subsequent oxidative coupling reaction proceeded smoothly
using thiophen-3-ylboronic acid to generate the desired prod-
uct 4al in 62 % yield, but no desired product 4am was obtained
using the (1H-pyrrol-3-yl)boronic acid. Furthermore, biphenyl,
Table 1. Optimization of the one-pot approach to phenolic ester.[a]
Entry
Ratio of 1a:3a
Oxidant
Solvent
Yield [%][b]
1
2
3
4
5
6
7
8
0.5:1.0
0.5:1.0
0.5:1.0
0.5:1.0
0.5:1.0
0.5:1.0
0.5:1.0
0.5:1.0
0.5:1.0
0.5:1.0
0.5:1.0
0.5:1.0
0.5:0.7
0.5:0.4
0.5:0.4
H2O2 (30 % aq.)
m-CPBA
TBHP
DTBP
DDQ
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CHCl3
82
30
69
NR
NR
NR
38
30
13
21
62
79
86
88
NR
O2
H2O2 (30 % aq.)
H2O2 (30 % aq.)
H2O2 (30 % aq.)
H2O2 (30 % aq.)
H2O2 (30 % aq.)
H2O2 (30 % aq.)
H2O2 (30 % aq.)
H2O2 (30 % aq.)
H2O2 (30 % aq.)
DCE
9
toluene
1,4-dioxane
THF
CH3CN
CH3CN
CH3CN
CH3CN
10
11
12[c]
13
14
15[d]
[a] Reactions were performed by using benzoic acid 1a (0.5 mmol), methyl propiolate (0.6 mmol), triethylamine (0.1 mmol) in solvent (3.0 mL) for 4 h at 60°C;
then phenylboronic acid 3a (1.0 mmol), K2CO3 (1.0 mmol), oxidant (0.6 mmol) was added for 2 h at room temperature; equivalents were based on 1a;
NR= no reaction. [b] Isolated yield. [c] 1.6 equiv. of H2O2. [d] Without methyl propiolate.
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Table 2. Substrate scope of carboxylic acids with 3a.[a]
[a] Reaction conditions: aromatic carboxylic acid 1 (0.5 mmol), methyl propiolate (0.6 mmol), NEt3 (0.1 mmol), in CH3CN (3.0 mL) at 60°C for 4–10 h; then 3a
(0.4 mmol), K2CO3 (1.0 mmol), H2O2 (30 % aq. 0.6 mmol) was added at room temperature for 2 h; equivalents were based on 1, and the ratio 1:3a = 1.0: 0.8.
[b] Isolated yield; n.d. = not determined.
naphthyl and phenanthryl boronic acids were also suitable for
Insight into the mechanistic pathway of this reaction, numer-
the reaction, such as 4an, 4ao and 4ap in 82 %, 69 % and 67 %, ous control experiments were carried out (Scheme 2). Only a
respectively. However, no product was detected when the ali- slight decrease in yield was observed in the presence of a radi-
phatic boronic acid 3q was exploited as a substrate.
cal scavenger BHT or 1,1-diphenylethylene under the standard
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Table 3. Substrate scope of boronic acids with 1a.[a]
[a] Reaction conditions: 1a (0.5 mmol), methyl propiolate (0.6 mmol), NEt3 (0.1 mmol), in CH3CN (3.0 mL) at 60 °C for 4 h; then boronic acid (0.4 mmol), K2CO3
(1.0 mmol), H2O2 (30 % aq. 0.6 mmol) was added at room temperature for 2 h; equivalents were based on 1a, and the ratio 1a:3 = 1.0:0.8. isolated yield;
n.d. = not determined.
conditions expect TEMPO, thus a radical pathway is probably might proceed through a hydroxylation of substrate 3a to
unlikely to be proceeded (Scheme 2a). Surprisingly, the reaction phenol, which served as a nucleophile to attack α-acyl enol
was quenched using anhydrous TBHP (5.5 mol/L in decane) ester 2a. To demonstrate this process we performed a reaction,
(Scheme 2b). In contrast, desired product 4aa was obtained in utilizing 3a under the standard reaction conditions. The phenol
a yield of 56 % when 18O-labeled H2O was added (Scheme 2c), was isolated with a yield of 72 %, which reacted with 2a to
which clearly indicated that H2O has an important role in the produce product 4aa at 85 % chemical yield (Scheme 2d). Addi-
reaction. However, there was no 18O-4aa was determined by tionally, good yield of the desired product was obtained when
GC–MS analysis. These experiments suggested that the reaction the reaction of commercial phenol and 2a was performed with
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Scheme 2. Control experiments and proposed mechanism.
or without water addition (Scheme 2e). On the basis of these using our reported coupling reagent methyl propiolate (entries
data and previous reports,[17] a feasible mechanism is depicted 4 and 5). The above results suggested that this acyl activation
in Scheme 2f. Initially, the oxidation of phenylboronic acid by platform achieved an advantage in the direct esterification of
H2O2 to generate the intermediate A, which undergoes a carboxylic acids.
rearrangement to produce species B. This intermediate B can
be converted into the corresponding phenol by hydrolysis.
Table 4. Comparative study of coupling reagents/methyl propiolate.[a]
Then, adduct 2a, generated from benzoic acid and methyl pro-
piolate, reacts with the phenol to form the final phenolic ester
4aa.
To compare the differences between conventional coupling
Entry
Coupling reagent
Time [h]
Time [h]
Yield [%][b]
reagents and methyl propiolate, the oxidative coupling reaction
of 1a with 3a was determined. As showed in Table 4, when the
coupling reagents BOP and DCC were employed, only 31 % and
24 % yield of coupling product 4aa was obtained, respectively
(entries 1 and 3). However, no desired product was detected in
the presence of HATU (entry 2). Although an acceptable yield
(65 % yield) was observed when using the combination rea-
gents of EDCI and HOBt, the reaction efficiency was lower than
1
2
3
4
5
BOP
HATU
DCC
EDCI + HOBt
Methyl propiolate
8
6
3
4
4
3
2
2
2
2
31
0
24
65
88
[a] Reaction conditions: 1a (0.5 mmol), coupling reagent (0.6 mmol), NEt3
(0.1 mmol), in CH3CN (3.0 mL) at 60 °C; then 3a (0.4 mmol), K2CO3 (1.0 mmol),
H2O2 (30 % aq. 0.6 mmol) was added at room temperature. [b] Isolated yield.
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7.9 Hz, 2H), 7.30–7.10 (m, 3H), 7.05–6.90 (m, 2H), 3.88 (s, 3H). 13C
NMR (100 MHz, CDCl3) δ 164.8, 163.9, 151.1, 132.2, 129.4, 125.6,
121.8, 113.8, 55.4.
Conclusion
In summary, we have reported a novel, highly efficient and en-
vironmentally friendly protocol for accessing phenolic esters
through an enol ester intermediate induced oxidative coupling
of carboxylic acids and arylboronic acids. Mild reaction condi-
tions, metal-free catalysis with green oxidant, simple operation,
good functional group tolerance, high reaction efficiency, all of
these make this strategy to be an alternative method for the
generation of esters.
Phenyl 3-methoxybenzoate (4ea). white solid; 73 mg, 80 % yield;
1H NMR (400 MHz, CDCl3) δ 7.81 (d, J = 7.7 Hz, 1H), 7.70 (s, 1H),
7.47–7.37 (m, 3H), 7.31–7.14 (m, 4H), 3.88 (s, 3H). 13C NMR (100 MHz,
CDCl3) δ 159.7, 151.0, 130.9, 129.5, 125.8, 122.6, 121.6, 120.1, 114.5,
55.5.
Phenyl 3,5-dimethoxybenzoate (4fa). colorless oil; 75 mg, 73 %
yield; 1H NMR (400 MHz, CDCl3) δ 7.47–7.38 (m, 2H), 7.34 (d, J =
2.4 Hz, 2H), 7.30–7.23 (m, 1H), 7.21 (d, J = 7.6 Hz, 2H), 6.72 (t, J =
2.3 Hz, 1H), 3.85 (s, 6H). 13C NMR (100 MHz, CDCl3) δ 164.9, 160.8,
151.0, 131.4, 129.4, 125.8, 121.6, 107.7, 106.4, 55.6.
Experimental Sections
General Information.
Phenyl 2-fluorobenzoate (4ga). colorless oil; 65.6 mg, 76 % yield;
1H NMR (400 MHz, CDCl3) δ 8.10 (m, 1H), 7.59 (m, 1H), 7.43 (t, J =
7.9 Hz, 2H), 7.31–7.15 (m, 5H). 19F NMR (300 MHz, CDCl3) δ –108.61.
13C NMR (100 MHz, CDCl3) δ 163.6, 162.7, 161.0, 150.7, 135.1, 132.5,
129.4, 126.0, 124.1, 121.6, 117.3, 117.0.
All commercially available reagents were used without purification
unless otherwise noted. Column chromatography was performed
using silica gel (100–200 mesh). Visualization of the compounds
was accomplished with UV light (254 nm) and iodine. NMR spectra
were recorded on Broker Advance spectrometers. 1H NMR spectra
were recorded at 400 MHz, 13C NMR spectra at 100 MHz and 19F
NMR spectra at 300 MHz and 400 MHz correspondingly with meth-
amphetamine or solvent (CDCl3, [D6]DMSO) as internal standard.
Chemical shifts are reported in values δ (ppm) and coupling con-
stants given in Hertz (Hz). Splitting patterns are designated as s
(singlet), d (doublet), t (triplet), and m (multiple). Gas chromatogra-
phy-mass spectrometry (GC–MS) was performed on Thermo DSQ II.
Phenyl 3-chlorobenzoate (4ha). colorless oil; 57.1 mg, 62 % yield;
1H NMR (400 MHz, CDCl3) δ 6.61 (s, 1H), 6.51 (d, J = 6.6 Hz, 1H),
6.03 (d, J = 8.0 Hz, 1H), 5.93–5.78 (m, 3H), 5.70 (m, 1H), 5.64 (t, J =
8.6 Hz, 2H). 13C NMR (100 MHz, CDCl3) δ 163.9, 150.7, 134.8, 133.6,
131.4, 130.2, 129.9, 129.5, 128.2, 126.1, 121.5.
Phenyl 4-chlorobenzoate (4ia). colorless oil; 64.2 mg, 69 %yield; 1H
NMR (400 MHz, CDCl3) δ 8.13 (d, J = 8.7 Hz, 2H), 7.47 (t, J = 5.5 Hz,
2H), 7.43 (m, 2H), 7.27 (t, J = 7.0 Hz, 1H), 7.23–7.15 (m, 2H). 13C NMR
(100 MHz, CDCl3) δ 164.3, 150.8, 140.1, 131.5, 129.5, 128.9, 128.1,
126.0, 121.6.
General Procedure for the Synthesis of Phenolic Esters.
A mixture of benzoic acid (0.5 mmol), methyl propiolate (0.6 mmol),
triethylamine (0.1 mmol) was added a 10 mL tube along with a
magnetic stir bar, and then 3.0 mL CH3CN was add. The tube was
sealed and stirred at 60 °C for 4 h. Next boronic acid (0.4 mmol),
K2CO3 (1.0 mmol) and 30 % H2O2 (0.6 mmol) was added the tube.
And the tube was sealed again and stirred at 60 °C for 2 h. The
mixture was filtered and the solvent removed under reduced pres-
sure and the residue was loaded on a silica gel column and flashed
with 10–25 % ethyl acetate in petroleum ether to afford the desired
product.
Phenyl 2-naphthoate (4la). colorless oil; 76.8 mg, 77 %yield; 1H
NMR (400 MHz, CDCl3) δ 8.78 (s, 1H), 8.19 (d, J = 8.6 Hz, 1H), 7.98
(d, J = 8.0 Hz, 1H), 7.95–7.84 (m, 2H), 7.59 (m, 2H), 7.45 (m, 2H), 7.28
(t, J = 8.4 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 165.3, 151.1, 135.8,
132.5, 131.9, 129.5, 128.6, 128.4, 127.8, 126.8, 125.9, 125.4, 121.7.
Phenyl furan-3-carboxylate (4ma). colorless oil; 61.6 mg,
82 %yield; 1H NMR (400 MHz, CDCl3) δ 8.12 (s, 1H), 7.42 (t, J = 1.7 Hz,
1H), 7.33 (t, J = 7.9 Hz, 2H), 7.18 (t, J = 7.4 Hz, 1H), 7.11 (d, J =
8.7 Hz, 2H), 6.79 (s, 1H). 13C NMR (100 MHz, CDCl3) δ 161.3, 150.4,
148.6, 144.0, 129.4, 125.9, 121.6, 118.9, 110.0.
3-Methoxy-3-oxoprop-1-en-1-yl benzoate (2a). colorless oil;
99.1 mg, 96 % yield; 1H NMR (400 MHz, CDCl3) δ 8.55 (d, J = 12.5 Hz,
1H), 8.12 (d, J = 7.2 Hz, 2H), 7.65 (t, J = 8.0 Hz, 1H), 7.57–7.41 (m,
2H), 5.91 (d, J = 12.5 Hz, 1H), 3.78 (s, 3H). 13C NMR (100 MHz, CDCl3)
δ 166.5, 162.4, 150.0, 134.3, 130.3, 128.7, 127.7, 106.0, 51.5.
Phenyl thiophene-2-carboxylate (4na). colorless oil; 75.5 mg,
93 %yield; 1H NMR (400 MHz, CDCl3) δ 7.98 (m, 1H), 7.65 (m, 1H),
7.42 (t, J = 7.9 Hz, 2H), 7.31–7.19 (m, 3H), 7.19–7.12 (m, 1H). 13C
NMR (100 MHz, CDCl3) δ 160.5, 150.6, 134.6, 133.4, 133.0, 129.4,
128.0, 125.9, 121.6.
1
Phenyl benzoate (4aa). colorless oil; 69.7 mg, 88 % yield; H NMR
(400 MHz, CDCl3) δ 8.20 (d, J = 7.7 Hz, 2H), 7.62 (t, J = 7.4 Hz, 1H),
7.49 (t, J = 7.8 Hz, 2H), 7.42 (t, J = 7.9 Hz, 2H), 7.30–7.14 (m, 3H).
13C NMR (100 MHz, CDCl3) δ 165.1, 151.0, 133.5, 130.1, 129.5, 128.5,
125.8, 121.7.
Phenyl 1H-indole-2-carboxylate (4oa). yellow solid; 68.9 mg,
73 %yield; 1H NMR (400 MHz, CDCl3) δ 9.29 (s, 1H), 7.72 (d, J =
8.1 Hz, 1H), 7.43 (t, J = 7.9 Hz, 3H), 7.34 (m, 2H), 7.32–7.20 (m, 3H),
7.17 (t, J = 7.2 Hz, 1H). 13C NMR (100 MHz, CDCl3) δ 160.5, 150.5,
137.4, 129.5, 127.5, 126.4, 126.0, 122.8, 121.6, 121.0, 112.0, 110.3.
Phenyl 4-methylbenzoate (4ba). white solid; 60.2 mg, 71 % yield;
1H NMR (400 MHz, CDCl3) δ 8.09 (d, J = 8.2 Hz, 2H), 7.42 (t, J =
7.9 Hz, 2H), 7.34–7.15 (m, 5H), 2.45 (s, 3H). 13C NMR (100 MHz,
CDCl3) δ 164.9, 160.8, 151.0, 131.4, 129.4, 125.9, 121.6, 107.7, 106.4,
55.6.
1
Phenyl cinnamate (4pa). colorless oil; 72.6 mg, 81 %yield; H NMR
(400 MHz, CDCl3) δ 7.87 (d, J = 16.0 Hz, 1H), 7.64–7.54 (m, 2H), 7.41
(m, 5H), 7.24 (t, J = 7.4 Hz, 1H), 7.17 (d, J = 8.6 Hz, 2H), 6.63 (d, J =
16.0 Hz, 1H). 13C NMR (100 MHz, CDCl3) δ 165.3, 150.8, 146.5, 134.2,
130.6, 129.4, 129.0, 128.3, 125.7, 121.6, 117.4.
Phenyl 3,4-dimethylbenzoate (4ca). white solid; 75.9 mg, 84 %
yield; 1H NMR (400 MHz, CDCl3) δ 7.99–7.89 (m, 2H), 7.42 (t, J =
7.9 Hz, 2H), 7.26 (m, 2H), 7.20 (d, J = 7.6 Hz, 2H), 2.34 (s, 6H). 13C
NMR (100 MHz, CDCl3) δ 165.4, 151.1, 143.0, 136.9, 131.2, 129.8,
129.4, 127.7, 127.1, 125.7, 121.7, 20.0, 19.6.
p-Tolyl benzoate (4ab). colorless oil; 75.8 mg, 89 %yield; 1H NMR
(400 MHz, CDCl3) δ 8.19 (m, 2H), 7.69–7.55 (m, 1H), 7.54–7.42 (m,
2H), 7.28–7.14 (m, 2H), 7.09 (d, J = 8.4 Hz, 2H), 2.36 (s, 3H). 13C NMR
(100 MHz, CDCl3) δ 165.3, 148.8, 135.4, 133.4, 129.9, 128.5, 121.3,
Phenyl 4-methoxybenzoate (4da). white solid; 75.7 mg, 83 % yield;
1H NMR (400 MHz, CDCl3) δ 8.15 (d, J = 9.0 Hz, 2H), 7.41 (t, J = 20.8.
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O-tolyl benzoate (4ac). colorless oil; 44.1 mg, 52 %yield; 1H NMR
(400 MHz, CDCl3) δ 8.34–8.14 (m, 2H), 7.63 (t, J = 7.4 Hz, 1H), 7.51
(t, J = 7.7 Hz, 2H), 7.31–7.08 (m, 4H), 2.23 (s, 3H). 13C NMR (100 MHz,
Naphthalen-2-yl benzoate (4ao). white solid; 68.4 mg, 69 %yield;
1H NMR (400 MHz, CDCl3) δ 8.31–8.19 (m, 2H), 7.91–7.76 (m, 3H),
7.68 (d, J = 2.1 Hz, 1H), 7.62 (t, J = 8.0 Hz, 1H), 7.54–7.42 (m, 4H),
CDCl3) δ 164.8, 149.6, 133.5, 131.1, 130.2, 128.6, 126.9, 126.0, 122.0, 7.35 (m, 1H). 13C NMR (100 MHz, CDCl3) δ 165.3, 148.7, 133.9, 133.6,
16.2.
131.6, 130.2, 129.7, 129.5, 128.6, 127.8, 126.6, 125.7, 121.3, 118.7.
4-(tert-Butyl)phenyl benzoate (4ad). white solid; 71.1 mg,
70 %yield; H NMR (400 MHz, CDCl3) δ 8.20 (d, J = 8.5 Hz, 2H), 7.60
(t, J = 7.4 Hz, 1H), 7.48 (t, J = 7.7 Hz, 2H), 7.43 (d, J = 8.7 Hz, 2H),
7.14 (d, J = 8.7 Hz, 2H), 1.33 (s, 9H). 13C NMR (100 MHz, CDCl3) δ
165.3, 148.7, 133.4, 130.1, 128.5, 126.3, 121.0, 34.5, 31.4.
Phenanthren-9-yl benzoate (4ap). colorless oil; 79.8 mg, 67 %yield;
1H NMR (400 MHz, CDCl3) δ 8.71 (d, J = 8.3 Hz, 1H), 8.66 (d, J =
8.1 Hz, 1H), 8.41–8.30 (m, 2H), 8.01 (d, J = 7.3 Hz, 1H), 7.86 (d, J =
9.1 Hz, 1H), 7.77–7.45 (m, 8H). 13C NMR (100 MHz, CDCl3) δ 165.2,
145.2, 133.8, 131.6, 130.3, 129.5, 129.0, 128.8, 128.5, 127.4–126.8,
126.7, 126.5, 123.0, 122.7, 122.0, 117.9.
1
4-(Benzyloxy)phenyl benzoate (4ae). white solid; 75.4 mg,
1
62 %yield; H NMR (400 MHz, CDCl3) δ 8.19 (d, J = 7.1 Hz, 2H), 7.61
(t, J = 6.8 Hz, 1H), 7.49 (t, J = 7.7 Hz, 2H), 7.42 (d, J = 7.1 Hz, 2H),
7.37 (t, J = 7.3 Hz, 2H), 7.31 (t, J = 8.1 Hz, 2H), 6.92–6.85 (m, 2H),
6.83 (d, J = 9.8 Hz, 1H), 5.05 (s, 2H). 13C NMR (100 MHz, CDCl3) δ
165.0, 159.8, 152.0, 136.7, 133.6, 130.2, 129.9, 129.6, 128.6, 128.0,
127.5, 114.2, 112.6, 108.7, 70.3.
Acknowledgments
This work was supported by Shanghai University of Engineering
Science and the Innovation Research Projects (nhrc-2015–15,
201810856017, cs1704006). We are grateful to the China Post-
doctoral Science Foundation (2016M601681), and the Opening
Project of Shanghai Key Laboratory of Chemical Biology for fi-
nancial support.
2-Fluorophenyl benzoate (4af). colorless oil; 50.1 mg, 58 %yield;
1H NMR (400 MHz, CDCl3) δ 8.21 (d, J = 7.7 Hz, 2H), 7.63 (t, J =
7.4 Hz, 1H), 7.50 (t, J = 7.7 Hz, 2H), 7.30–7.01 (m, 4H). 13C NMR
(100 MHz, CDCl3) δ 164.1, 155.5, 153.0, 138.4, 133.8, 130.3, 128.8,
128.6, 127.1, 124.4, 123.9, 116.7.
Keywords: Enol Ester Intermediate · Esterification · Metal-
Free · Oxidative Coupling · Arylboronic Acid
4-Fluorophenyl benzoate (4ag). colorless oil; 45.8 mg, 54 %yield;
1H NMR (400 MHz, CDCl3) δ 8.19 (d, J = 7.1 Hz, 2H), 7.63 (t, J =
6.8 Hz, 1H), 7.51 (t, J = 7.7 Hz, 2H), 7.18 (m, 2H), 7.10 (t, J = 8.6 Hz,
2H). 19F NMR (300 MHz, CDCl3) δ –117.19. 13C NMR (100 MHz, CDCl3)
δ 165.1, 161.5, 159.1, 146.8, 133.6, 130.1, 129.3, 128.6, 123.1, 116.2,
116.0.
[1] a) P. Jia, M. Zhang, L. H. Hu, G. D. Feng, C. Y. Bo, Y. H. Zhou, ACS Sustaina-
ble Chem. Eng. 2015, 3, 2187; b) D. Gray, C. Concellon, T. Gallagher, K. E.
Homologation, J. Org. Chem. 2004, 69, 4849; c) J. F. Kennedey, H. Kumar,
P. S. Panesar, S. S. Marwaha, R. Goyal, A. Parmar, S. Kaur, J. Chem. Technol.
Biotechnol. Biotechnol. 2006, 81, 866; d) M. J. L. Tschan, N. S. Ieong, R.
Todd, J. Everson, A. P. Dove, Angew. Chem. Int. Ed. 2017, 56, 16664;
Angew. Chem. 2017, 129, 16891.
[2] a) T. Yasukawa, X. Yang, S. Kobayashi, Org. Lett. 2018, 20, 5172; b) S.
Chun, Y. K. Chung, Org. Lett. 2017, 19, 3787; c) R. S. Reddy, J. N. Rosa,
L. F. Veiros, S. Caddick, P. M. P. Gois, Org. Biomol. Chem. 2011, 9, 3126; d)
J. N. Rosa, R. S. Reddy, N. R. Candeias, P. M. S. D. Cal, P. M. Gois, Org. Lett.
2010, 12, 2686.
1
3-Chlorophenyl benzoate (4ah). white solid; 65 mg, 70 %yield; H
NMR (400 MHz, CDCl3) δ 8.18 (m, 2H), 7.63 (t, J = 7.4 Hz, 1H), 7.50
(t, J = 7.7 Hz, 2H), 7.34 (t, J = 8.2 Hz, 1H), 7.25 (t, J = 3.8 Hz, 2H),
7.13 (d, J = 8.7 Hz, 1H). 13C NMR (100 MHz, CDCl3) δ 164.7, 151.5,
134.7, 133.8, 130.2, 129.1, 128.6, 126.1, 122.4, 120.1.
2-Bromophenyl benzoate (4ai). colorless oil; 69.5 mg, 63 %yield;
1H NMR (400 MHz, CDCl3) δ 8.25 (m, 2H), 7.72–7.56 (m, 2H), 7.51 (t,
J = 7.7 Hz, 2H), 7.41–7.31 (m, 1H), 7.27 (d, J = 8.1 Hz, 1H), 7.14 (t,
J = 7.7 Hz, 1H). 13C NMR (100 MHz, CDCl3) δ 164.2, 148.5, 133.8,
133.4, 130.4, 129.0, 128.5, 127.3, 123.9, 116.3.
[3] a) D. S. Mannel, M. S. Ahmed, T. W. Root, S. S. Stahl, J. Am. Chem. Soc.
2017, 139, 1690; b) K. Kaizuka, H. Miyamura, S. Kobayashi, J. Am. Chem.
Soc. 2010, 132, 15096.
4-Nitrophenyl benzoate (4aj). white solid; 88.4 mg, 91 %yield; 1H
NMR (400 MHz, CDCl3) δ 8.21 (m, 2H), 8.16 (m, 2H), 7.68 (m, 1H),
7.61 (d, J = 7.4 Hz, 2H), 7.55 (t, J = 7.7 Hz, 2H). 13C NMR (100 MHz,
CDCl3) δ 164.5, 151.3, 148.9, 134.1, 130.3, 130.0, 128.7, 128.2, 120.8,
117.5.
[4] a) J. B. Peng, F. P. Wu, C. Xu, X. X. Qi, J. Ying, X. F. Wu, IScience 2018, 8,
175; b) J. Liu, K. Dong, R. Franke, H. Neumann, R. Jackstell, M. Beller, J.
Am. Chem. Soc. 2018, 140, 10282; c) M. B. Ibrahim, R. Suleiman, M. Fet-
touhi, B. E. Ali, RSC Adv. 2016, 6, 78826; d) K. Dong, R. Sang, X. Fang, R.
Franke, A. Spannenberg, H. Neumann, R. Jackstell, M. Beller, Angew.
Chem. Int. Ed. 2017, 56, 5267; Angew. Chem. 2017, 129, 5351.
[5] a) S. Dupuy, D. Gasperini, S. P. Nolan, ACS Catal. 2015, 5, 6918; b) S. J.
Xu, J. Q. Liu, D. H. Hu, X. H. Bi, Green Chem. 2015, 17, 184; c) N. Panda,
P. Mishra, I. Mattan, J. Org. Chem. 2016, 81, 1047; d) N. Panda, R. Moth-
kuri, A. Pal, A. R. Paital, Adv. Synth. Catal. 2013, 355, 2809; e) H. Huang,
X. S. Zhang, C. G. Yu, X. M. Li, Y. T. Zhang, W. Wang, ACS Catal. 2016, 6,
8030.
3,5-Dichlorophenyl benzoate (4ak). colorless oil; 63 mg, 59 %yield;
1H NMR (400 MHz, CDCl3) δ 8.16 (m, 2H), 7.66 (t, J = 7.5 Hz, 1H),
7.52 (t, J = 7.7 Hz, 2H), 7.29 (t, J = 1.8 Hz, 1H), 7.19 (d, J = 1.8 Hz,
2H). 13C NMR (100 MHz, CDCl3) δ 164.3, 151.6, 135.3, 134.0, 130.2,
128.7, 126.3, 121.0.
[6] a) A. M. Simion, I. Hashimoto, Y. Mitoma, N. Egashira, C. Simion, Synth.
Commun. 2012, 42, 921; b) R. Murashige, Y. Hayashi, S. Ohmori, A. Torii,
Y. Aizu, Y. Muto, Y. Murai, Y. Oda, M. Hashimoto, Tetrahedron 2011, 67,
641; c) H. X. Liu, Y. Q. Da ng, Y. F. Yuan, Z. F. Xu, S. X. Qiu, H. B. Tan, Org.
Lett. 2016, 18, 5584; d) H. M. Yang, C. C. Huang, Catal. Lett. 2009, 128,
235; e) C. Wiles, P. Watts, S. J. Haswell, Tetrahedron 2003, 59, 10173.
[7] a) T. X. Metro, J. Bonnamour, T. Reidon, A. Duprez, J. Sarpoulet, J. Marti-
nez, F. Lamaty, Chem. Eur. J. 2015, 21, 12787; b) L. L. Chng, J. Yang, J. Y.
Ying, ChemSusChem 2015, 8, 1916; c) C. T. Chen, Y. S. Munot, J. Org.
Chem. 2005, 70, 8625; d) J. S. Ruso, N. Rajendiran, R. S. Kumaran, Tetrahe-
dron Lett. 2014, 55, 2345.
1
Thiophen-3-yl benzoate (4al). colorless oil; 50.6 mg, 62 %yield; H
NMR (400 MHz, CDCl3) δ 8.17 (m, 2H), 7.62 (t, J = 7.4 Hz, 1H), 7.49
(t, J = 7.7 Hz, 2H), 7.33–7.26 (m, 1H), 7.24 (d, J = 3.3 Hz, 1H), 7.05
(m, 1H). 13C NMR (100 MHz, CDCl3) δ 164.2, 147.2, 133.6, 130.1,
129.3, 128.6, 124.2, 121.4, 111.0.
[1,1′-biphenyl]-4-yl benzoate (4an). white solid; 90 mg, 82 %yield;
1H NMR (400 MHz, CDCl3) δ 8.22 (d, J = 7.4 Hz, 2H), 7.63 (d, J =
8.6 Hz, 3H), 7.58 (d, J = 7.7 Hz, 2H), 7.51 (t, J = 7.7 Hz, 2H), 7.44 (t,
J = 7.6 Hz, 2H), 7.34 (t, J = 7.3 Hz, 1H), 7.29 (d, J = 8.6 Hz, 2H). 13C
NMR (100 MHz, CDCl3) δ 165.2, 150.4, 140.4, 139.0, 133.6, 130.2,
129.6, 128.8, 128.6, 128.2, 127.4, 127.1, 122.0.
[8] a) N. Jalalian, T. B. Petersen, B. Olofsson, Chem. Eur. J. 2012, 18, 14140;
b) T. B. Petersen, R. Khan, B. Olofsson, Org. Lett. 2011, 13, 3462.
Eur. J. Org. Chem. 0000, 0–0
www.eurjoc.org
7
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Full Paper
[9] S. H. Xie, S. Yang, C. X. Zhang, M. R. Ding, M. Liu, J. Guo, F. Z. Zhang, J.
Org. Chem. 2017, 82, 5250.
[13]
[14]
W. Y. Yin, H. F. He, Y. Zhang, T. Long, Chem. Asian J. 2014, 9, 2402.
a) L. Hu, S. L. Xu, Z. G. Zhao, Y. Yang, Z. Y. Peng, M. Yang, C. L. Wang, J. F.
Zhao, J. Am. Chem. Soc. 2016, 138, 13135; b) T. Krause, S. Baader, B. Erb,
L. J. Gooꢀen, Nat. Commun. 2016, 7, 11732; c) Y. Z. Wang, Z. X. Wang,
Y. X. Li, G. D. Wu, Z. Cao, L. M. Zhang, Nat. Commun. 2014, 5, 3470.
a) X. J. Xu, L. L. Huang, X. H. Liu, H. D. Feng, J. Org. Chem. 2018, 83, 7962;
b) X. J. Xu, L. L. Huang, X. Y. Yin, E. V. Van der Eycken, Org. Chem. Front.
2018, 5, 2955.
[10] a) T. Dohi, D. Koseki, K. Sumida, K. Okada, S. Mizuno, A. Kato, K. Mori-
moto, Y. Kita, Adv. Synth. Catal. 2017, 359, 3503; b) V. Arun, M. Pilania, D.
Kumar, Chem. Asian J. 2016, 11, 3345; c) B. Bhattarai, J. H. Tay, P. Nagorny,
Chem. Commun. 2015, 51, 5398; d) T. L. Seidl, D. R. Stuart, J. Org. Chem.
2017, 82, 11765.
[11] a) N. Devarajan, P. Suresh, Org. Chem. Front. 2018, 5, 2322; b) C. E. Jacob-
son, N. Martinez-Muñoz, D. G. Gorin, J. Org. Chem. 2015, 80, 7305; c) L. L.
Zhang, G. Y. Zhang, M. L. Zhang, J. Cheng, J. Org. Chem. 2010, 75, 7472;
d) J. J. Dai, J. H. Liu, D. F. Luo, L. Liu, Chem. Commun. 2011, 47, 677.
[12] a) L. J. Gooßen, K. Ghosh, Angew. Chem. Int. Ed. 2001, 40, 3458; Angew.
Chem. 2001, 113, 3566; b) P. Lei, G. R. Meng, S. C. Shi, Y. Ling, Chem. Sci.
2017, 8, 6525; c) T. B. Halima, W. Y. Zhang, I. Yalaoui, X. Hong, Y. F. Yang,
K. N. Houk, S. G. Newman, J. Am. Chem. Soc. 2017, 139, 1311; d) H.
Tatamidani, F. Kakiuchi, N. Chatani, Org. Lett. 2004, 6, 3597; e) B. W. Xin,
Y. H. Zhang, K. Cheng, J. Org. Chem. 2006, 71, 5725; f) S. C. Shi, P. Lei, M.
Szostak, Organometallics 2017, 36, 3784; g) A. H. Dardi, P. R. Melvin, R. M.
Davis, N. Hazari, M. Mohadjer Beromi, J. Org. Chem. 2018, 83, 469.
[15]
[16]
a) W. R. Leow, J. C. Yu, B. Li, B. H. Hu, W. Li, X. D. Chen, Angew. Chem. Int.
Ed. 2018, 57, 9780; Angew. Chem. 2018, 130, 9928; b) J. Simon, S. Salz-
brunn, G. K. S. Prakash, N. A. Petasis, G. A. Olah, J. Org. Chem. 2001, 66,
633; c) A. Gualandi, A. Savoini, R. Saporetti, P. Franchi, M. Lucarini, G.
Cozzi, Org. Chem. Front. 2018, 5, 1573; d) W. Z. Weng, H. Liang, Bo. Zhang,
Org. Lett. 2018, 20, 4979.
a) see ref.[16b]; b) E. Saikia, S. J. Bora, B. Chetia, RSC Adv. 2015, 5, 102723.
[17]
Received: January 27, 2019
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EsterificationAbstract
X. Xu, H. Feng,* H. Li, L. Huang ..... 1–9
Enol Ester Intermediate Induced
Metal-Free Oxidative Coupling of
Carboxylic Acids and Arylboronic
Acids
Direct esterification of carboxylic acids mediate-induced metal-free oxidative
with arylboronic acids has been suc- coupling. Metal-free, simple operation,
cessfully developed employing methyl good functional group tolerance, all of
propiolate as an activating reagent. these indicate that this method is an
This transformation was performed adoptable approach for the formation
through a process of enol ester inter- of phenolic esters.
DOI: 10.1002/ejoc.201900137
Eur. J. Org. Chem. 0000, 0–0
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9
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim