Copper-mediated simple and direct aerobic oxidative esterification of arylacetonitriles with alcohols/phenols

Article abstract of DOI:10.1002/aoc.6073

A simple and direct aerobic oxidative esterification reaction of arylacetonitriles with alcohols/phenols is achieved in the presence of a copper salt and molecular oxygen, which produces a broad range of aryl carboxylic acid esters in good to high yields. Copper salt plays multiple roles in the transformation, which allows the oxygenation of C-H bond, cleavage of inert C-C bond, and formation of C-O bond in one pot without the assistance of any of the acids, bases, ligands, and so on. The reaction provides a simple, direct, and efficient protocol towards functionalized esters, especially aryl benzoates, from readily available starting materials.

Full text of DOI:10.1002/aoc.6073

Received: 17 August 2020
DOI: 10.1002/aoc.6073
Revised: 29 September 2020
Accepted: 5 October 2020
F U L L P A P E R
Copper-mediated simple and direct aerobic oxidative
esterification of arylacetonitriles with alcohols/phenols
Jianyu Dong1,2
| Xiuling Chen2,3 | Fangyan Ji2 | Lixin Liu2 | Lebin Su2
|
Min Mo1 | Jian-Sheng Tang1 | Yongbo Zhou2
1Department of Educational Science,
A simple and direct aerobic oxidative esterification reaction of arylacetonitriles
with alcohols/phenols is achieved in the presence of a copper salt and molecu-
lar oxygen, which produces a broad range of aryl carboxylic acid esters in good
to high yields. Copper salt plays multiple roles in the transformation, which
allows the oxygenation of C H bond, cleavage of inert C C bond, and
formation of C O bond in one pot without the assistance of any of the acids,
bases, ligands, and so on. The reaction provides a simple, direct, and efficient
protocol towards functionalized esters, especially aryl benzoates, from readily
available starting materials.
Hunan First Normal University,
Changsha, China
2College of Chemistry and Chemical
Engineering, Hunan University,
Changsha, China
3Non-power Nuclear Technology
Collaborative Innovation Center, School
of Nuclear Technology and Chemistry &
Biology, Hubei University of Science and
Technology, Xianning, China
Correspondence
Jianyu Dong, Department of Educational
Science, Hunan First Normal University,
Changsha 410205, China.
K E Y W O R D S
aerobic oxidative esterification, alcohols/phenols, arylacetonitriles, copper salt, esters
Email: dongjianyu@hnu.edu.cn
Funding information
National Natural Science Foundation of
China, Grant/Award Numbers: 21706058,
21878072, 21573065; Hunan Provincial
Natural Science Foundation of China,
Grant/Award Number: 2020JJ2011;
Research Foundation of Education Bureau
of Hunan Province, Grant/Award
Number: 16B054
1 | INTRODUCTION
derivatives.[9] Due to their extreme significance and
extensive applications in chemistry and chemical indus-
Esters are very common chemicals that are widely used
as precursors for various functional group transforma-
tions in organic synthesis. Ester groups, especially aryl
ester, are also versatile functional units in numerous
pharmaceuticals, agrochemicals, fragrances, and poly-
mers.[1,2] Traditional synthetic procedures for the prepa-
ration of esters rely on the transformations of carboxylic
acids and acid anhydrides,[3,4] Over the past decades,
alternative methods have been developed, such as trans-
formations of amides,[5] transesterifications of esters,[6]
the direct oxidative esterifications of aldehydes[7] and
hydrocarbons,[2b,8] and carbonylation reactions of arene
try, it still necessitates diverse methods for preparing
esters with facile operations, simple conditions, readily
available starting materials, broad substrate scope, and/or
step economy.
Herein, as a part of our ongoing research in copper
catalysis,[10] we report a simple and direct aerobic
oxidative esterification of easily available arylacetonitriles
with alcohols/phenols mediated by simple copper salt
(Scheme 1). This procedure successfully combines inert
C C bond cleavage,[11,12] C H bond oxygenation, and
C O bond formation in one pot from readily available
starting materials without the need for any of the acids,
Appl Organomet Chem. 2020;e6073.
wileyonlinelibrary.com/journal/aoc
© 2020 John Wiley & Sons, Ltd.
1 of 10
https://doi.org/10.1002/aoc.6073

2 of 10
DONG ET AL.
TABLE 1 Optimization of the reaction conditions
Entry
1
Catalyst
CuCl
T (ꢀC)
120
120
120
120
120
120
120
120
120
120
120
120
120
120
120
120
120
120
120
120
120
120
100
130
120
120
Solvent
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
DCE
Yield (%)a
43
SCHEME 1 Simple and direct approach to aryl esters
2
CuCl2
16
3
CuBr
4
bases, ligands, and so on and produces a broad range of
aryl carboxylic acid esters in good to high yields. Copper
salt acts as multiple roles in this reaction, that is,
catalyzing the Ritter-type oxidation of sp3C H bonds of
arylacetonitriles, activating the carbonyl groups of aryl
formyl cyanide intermediates, and improving the nucleo-
philicity of phenols.
Multiple roles of a metal catalyst, especially palla-
dium catalysts, have attracted extensive attention in
chemistry,[13] because diverse individual transformations
and chemical bond cleavage/formation can occur in a
one pot with the assistance of such a catalyst, which
makes a reaction simpler and consuming less. Over past
decades, copper salts have received great attention as
earth-abundant metal catalysts, readily available and
effective alternatives to noble metals due to their excel-
lent catalytic efficiency in diverse types of reactions.[14]
However, it is rare in copper chemistry that copper
catalysts play multiple roles in one-pot reaction.[15]
Undoubtedly, the multiple roles of copper salt promotes
the esterification reaction in a very simple and efficient
manner and avoids the employment of exotic additives
and reagents, which is interesting and attractive.
4
CuBr2
Trace
8
5
CuI
Cu0
6
40
7
Cu(NO3)2
Cu(OAc)2
Cu(OAc)2
FeBr3
32
8
9b
89
32
10
11
12
13
14
15
16
17
18
19
20c
21c,d
22c,e
23
24
25
26g
None
None
None
None
Trace
22
Mn(OAc)2
AgNO3
NiCl2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
—
Dioxane
Toluene
THF
21
18
EA
4
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
EtOH
None
None
None
None
Trace
60
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
CuCl
2 | RESULTS AND DISCUSSION
91 (83)f
94 (85)f
EtOH
Initially, phenylacetonitrile (1a) and ethanol (2a) were
chosen as model substrates to examine the reaction
parameters, and the results were summarized in Table 1.
The reaction of 1a and 2a gave ethyl benzoate (3a) in GC
40% yield in the presence of 50 mol% CuCl in CH3CN at
120ꢀC under the oxygen atmosphere (Table 1, Entry 1).
Then, copper salts were screened (Table 1, Entries 2–8),
Cu(OAc)2 showed the best catalytic efficiency, producing
3a in 89% yield (Table 1, Entry 8). A lower loading
(20 mol%) of Cu(OAc)2 resulted in a low yield of the
product (32%; Table 1, Entry 9). In contrast, FeBr3 that is
an efficient catalyst in an oxidative esterification
reaciton[12f] was ineffective for the reaction (Table 1,
Entry 10). Other transition metal catalysts such as Mn,
Ag, and Ni salts did not work either (Table 1, Entries
Note: Reaction conditions: phenylacetonitrile (1a, 0.2 mmol), ethanol (2a,
0.24 mmol), catalyst (50 mol%) based on 1a, solvent (1.0 ml), O2 (1 atm), and
sealed Schlenck tube of 25 ml.
aGC yield using dodecane as an internal standard.
b20 mol% Cu(OAc)2.
cN2 (1 atm).
d0.5 mmol H2O2 was employed as oxidant.
e0.5 mmol TBHP (tert-butylhydroperoxide) as oxidant.
fIsolated yields.
g100 mol% CuCl.
11–13). The effect of solvents was also investigated
(Table 1, Entries 14–18), and CH3CN was found to be the
best choice. The reaction proceeded neither in the
absence of the catalyst (Table 1, Entry 19) nor under

DONG ET AL.
3 of 10
the inert atmosphere (Table 1, Entry 20). By the replace-
ment of the oxidant with H2O2 or TBHP, the reaction did
not take place either (Table 1, Entries 21 and 22). The
reaction was sensitive to the temperature, it did not work
(Table 1, Entry 23) by lowering the temperature to 100ꢀC.
Meanwhile, the yield of 3a was sharply reduced (60%;
Table 1, Entry 24) at 130ꢀC. Notably, excellent yield (91%;
Table 1, Entry 25) of 3a was achieved by the conduction
of the reaction in 2a (1.0 ml) or by the replacement
of Cu(OAc)2 with CuCl (100 mol%, 94% yield; Table 1,
Entry 26).
With the optimized conditions in hand, the scope of
the reaction concerning for alcohols was investigated
(Table 2). All of the three kinds of alcohols reacted
smoothly with phenylacetonitrile (1a) to produce the
corresponding benzoates in good to high yields. The
aerobic oxidative esterification of phenylacetonitrile with
alkyl alcohols such as ethanol (2a), propyl alcohol (2b),
octanol (2c), and isoamyl alcohol (2d) produced the
corresponding alkyl benzoates in high yields (78–83%;
Table 2, Entries 1–4). When sterically hindered tertiary
alcohol t-butanol (2e) was used as a substrate, the desired
product (3e) was obtained in 69% yield (Table 2, Entry 5).
Benzyl alcohols were also good substrates for the reac-
tion, giving the corresponding benzyl benzoates in good
yields (71–74%; Table 2, Entries 6–10). The electronic var-
iation of substituents was not significantly influential on
the reaction efficiency. Comparable yields were observed
for the products bearing electron-donating (OMe, 74%)
and electron-withdrawing groups (NO2, 71%; CF3, 71%)
on the phenyl ring. Notably, the transformation of other
types of arylmethyl alcohols, such as sterically hindered
naphthyl methanols (naphthalen-1-ylmethanol and
naphthalen-2-ylmethanol) and heteroaryl methanols
of the substituent groups in the steps of Ritter-type oxida-
tion of benzyl C H bonds[16] and subsequent nucleo-
philic attack of ethanol at benzoyl cyanides in the
reaction. The electron-donating (electron-withdrawing)
groups facilitate (disfavor) oxidation of benzyl C H
bonds but disfavor (facilitate) the subsequent nucleo-
philic attack (vide infra). All of the substituted
2-phenylacetonitriles (electron-rich and electron-deficient
groups) shown slightly lower efficiency than that of
phenylacetonitrile (1a, 85% yield; Table 3, Entry 1). This
result indicated that the overall-electronic effect of
substituent groups is detrimental to the reaction.
2-(Naphthalen-2-yl) acetonitrile (1h) also served as a
good substrate, furnishing the desired ester (3u) in 76%
yield (Table 3, Entry 8). To our delight, a heteroaryl ester
3v was obtained (70% yield) by the treatment of
2-(thiophen-2-yl)acetonitrile 1i with 2a under the present
reaction system, indicating that this method will be an
efficient approach to introduce an aromatic heterocycle
into functional molecules (Table 3, Entry 9). Unfortu-
nately, when 2-(pyridin-3-yl)acetonitrile 1k was used
as substrate, the oxidative esterification reaction did
not take place, which was probably due to the strong
coordination between N atom and Cu cation (Table 3,
Entry 11).
It was noted that Song's group had pioneered a
Fe-catalyzed oxidative C CN bond cleavage of
phenylacetonitriles for the synthesis of esters.[12f]
Although it is very elegant, the toxic additive pyridine is
indispensable. By the replacement of copper salt with
FeBr3 that was used in Song's reaction system, the
reaction did not proceed. Therefore, this protocol is quite
different from Song's method.
Phenols have low nucleophilicity and are easily
oxidized to diverse compounds such as coupling
(furan-3-ylmethanol
and
thiophen-3-ylmethanol)
proceeded more efficiently than benzyl alcohols, giving
the corresponding esters in high yields (80–83%; Table 2,
Entries 11–14).
products, ortho-oxidation products, and polymers[14b–e]
;
aerobic oxidative esterification of precursors with phenols
cannot be easily achieved. To address this issue, an over-
stoichiometric amount of phenols are generally required,
and an additional additive base is also used to form
phenolic salts for facilitating the esterification.[12b,f]
Gratifyingly, phenols were suited for the present aerobic
oxidative esterification reaction using nearly equimolar
quantities of phenols (1.2 equiv). Phenols bearing both
electron-donating (methyl and OMe) and electron-
withdrawing (Cl−, Br−, and NO2) groups worked well, a
variety of functionalized phenyl benzoates were produced
in good to high isolated yields (67–77%, Table 4, Entries
1–6). Naphthol (2u) was also suited for the transforma-
tion, and naphthyl benzoate (3ze) was furnished in a 60%
yield (Table 4, Entry 7).
Next, the substrate scope of nitriles was investigated
(Table 3). 2-Phenylacetonitriles substituted with electron-
rich as well as those with electron-deficient groups could
undergo aerobic oxidative esterification with ethanol,
giving the corresponding esters in good to high yields
(71–80%). 2-Phenylacetonitriles substituted by methyl
(1b) and methoxyl (1c) groups work well as substrates
to give ester derivatives 3o and 3p in 72 and 71%
yields, respectively (Table 4, Entries 2 and 3). Slightly
better results were observed in the reaction of
2-phenylacetonitriles bearing electron-deficient groups
such as chloro (1d), bromo (1e), trifluoromethyl (1f), and
nitro (1g) groups with ethanol, and the corresponding
products 3q–3t were produced in 77–80% yields (Table 3,
Entries 4–7). Notably, there were different performances
To explore the reaction mechanism, several control
experiments were performed. By the replacement of 16O2

4 of 10
DONG ET AL.
TABLE 2 Substrate scope of alcohols 2
Entry
R
Product
Yield (%)
3a, 83
1
2
3
Et
2a
2b
2c
n-Propyl
n-Octoyl
3b, 82
3c, 79
4
tert-Amyl
2d
2e
2f
3d, 78
3e, 69
3f, 71
3g, 74
3h, 71
3i, 71
3j, 72
5
t-Bu
6
Benzyl
7
p-OMe-benzyl
p-CF3-benzyl
p-NO2-benzyl
1-Phenylethyl
2g
2h
2i
8
9
10
2j
11
12
Naphthalen-1-ylmethyl
Naphthalen-2-ylmethyl
2k
3k, 80
2l
3l, 81
13
14
Furan-3-ylmethyl
X = O
2m
2n
3m, 83
3n, 80
Thiophen-3-ylmethyl
X = S
Note: Reaction conditions: phenylacetonitrile (1a, 0.2 mmol), alcohol 2 (0.24 mmol), Cu(OAc)2 (50 mol%) based on 1a, CH3CN (1.0 ml), O2 (1 atm), 120ꢀC,
24 h, sealed Schlenck tube of 25 ml, and isolated yields.
18
with 18O2 (97 atom%), the O2 labeled product (3ze0) in
58% yield with quantitative incorporation of 18O2
(94.4 atom%) (Scheme 2, Equation 1; for details, see
Scheme S1 and Figure S1). These results suggested that
the O atom of the product came from the molecular oxy-
gen. The addition of butylated hydroxytoluene (BHT)
could restrain the reaction (Scheme 2, Equation 2); only
a 27% yield of 3a was observed, suggesting that a free

DONG ET AL.
5 of 10
TABLE 3 Substrate scope of nitriles 1
Entry
1
Product
Yield (%)
3a, 85(80)a
1
1a
1b
1c
2
3
3o, 72
3p, 71
4
5
6
1d
1e
1f
3q, 80
3r, 78
3s, 79
7
8
1g
3t, 77
1h
3u, 76
(Continues)

6 of 10
DONG ET AL.
TABLE 3 (Continued)
Entry
1
Product
Yield (%)
9b
1i
1j
3v, 70
10b
3w, 69
3x, n.d.
11
1k
Note: Reaction conditions: arylacetonitrile 1 (0.2 mmol), ethanol 2a (1.0 ml), CuCl (100 mol%) based on arylacetonitrile, O2 (1 atm), 120ꢀC, 24 h, sealed
Schlenck tube of 25 ml, and isolated yield.
a2-mmol scale.
b1.0-ml propyl alcohol instead of ethanol.
radical process might be involved in the present reaction.
The reaction of benzoic acid 4 with ethanol 2a did
not give 3a under the standard reaction conditions
(Scheme 2, Equation 3). Only a small amount of 3a (13%)
was observed from benzaldehyde 5 and ethanol 2a under
similar conditions (Scheme 2, Equation 4). These results
demonstrated that neither benzoic acid nor benzaldehyde
was the efficient intermediate for this transformation. In
the absence of the catalyst, benzoyl cyanide (6) reacted
with ethanol to produce 3a in 45% yield (Scheme 2,
Equation 5). Indeed, by the treatment of phen-
ylacetonitrile with 10 mol% Cu(OAc)2 in the absence of
ethanol, compound 6 was observed in 38% yield
(Scheme 2, Equation 6). These results suggested that
benzoyl cyanide was an efficient intermediate for this
transformation, and copper salt catalyzed the step of
Ritter-type oxidation of benzyl C H bonds to benzoyl
cyanides (Table 1, Entry 19). Expectedly, the addition of a
catalytic amount of Cu(OAc)2 (10 mol%) could remark-
ably improve the reaction efficiency (86% vs. 45% yield).
This result suggested that copper salt activated the
carbonyl group of benzoyl cyanides and facilitated the
addition-elimination of benzoyl cyanides with alco-
hols.[17] However, the stoichometric copper salt gave a
lower yield (61% vs. 86%) of the product, which was prob-
ably due to the interaction between the copper salt and
the oxygen atom of ethanol, and it decreased the nucleo-
philicity of ethanol. Similar results (28% and 55% yields
of 3y) were observed by the treatment of benzoyl cya-
nides with phenol in absence and in the presence of
10 mol% of copper salt, respectively (Scheme 2,
Equation 7). In a sharp contrast (vs. 61% yield of 3a),
much more yield (83%) of 3y was observed in the pres-
ence of stoichiometric Cu(OAc)2 (100 mol%). This result
suggested that phenolic anion (phenolic copper salt) was
produced, which increased the nucleophilicity of phenol
and facilitated its addition to benzoyl cyanide.
Based on the present results and the previous
literature,[12f,16a,17,18] a plausible reaction mechanism is
proposed for the copper-catalyzed oxidative synthesis of
ester (Scheme 3). Initially, in the presence of Cu/O2,
Ritter-type oxidation (free radical processes) of phen-
ylacetonitrile 1 takes place, giving aryl formyl cyanide III
via aryl methyl radical I and aryl methyl peroxy radical
II. The interaction between the carbonyl group of III and
cooper salt forms intermediate IV.[17] Then, the nucleo-
philic attack of the oxygen atom of alcohol/phenol at the
carbonyl group of IV forms intermediate V. Elimination

DONG ET AL.
7 of 10
TABLE 4 Substrate scope of phenols
Entry
2
Product
Yield (%)
1
2o
2p
3y, 77
2
3
3z, 71
2q
3za, 70
4
5
2r
2s
3zb, 69
3zc, 67
6
7
2t
3zd, 68
3ze, 60
2u
Note: Reaction conditions: phenylacetonitrile (1a, 0.2 mmol), phenols 2o–2r (0.24 mmol), Cu(OAc)2 (50 mol%) based on 1a, CH3CN (1.0 ml), O2 (1 atm), 120ꢀC,
24 h, sealed Schlenck tube of 25 ml, and isolated yield.

8 of 10
DONG ET AL.
SCHEME 2 Experimental probes of the reaction
mechanism
hampers the reaction, whereas the H Cu exchange
between phenol and copper salt (VI) that improves
the nucleophilicity of phenols facilitates the reaction.
Therefore, the lower loadings of the copper salt are used
for alcohols, and the higher loadings of copper salt are
required for phenols in the reaction.
3 | CONCLUSION
SCHEME 3 Possible reaction mechanism
We have successfully developed a simple, direct, and effi-
cient aerobic oxidative functionalization of inert C C
bond for the synthesis of esters from readily available
arylacetonitrile derivatives and alcohol/phenols pro-
moted by simple copper salt without any additives. This
method successfully realizes C H bond oxygenation,
C C bond activation, and C O bond formation in one
pot. A variety of alcohols and phenols are suitable sub-
strates for this transformation, providing a wide range of
functionalized esters. The copper salt was found to
play the multiple roles of the copper, such as catalyzing
the Ritter-type oxidation of sp3C H bonds of
arylacetonitriles, activating the carbonyl groups of aryl
of cyano group from V gives the desired ester 3. H Cu
exchange between alchohol/phenol and cooper salt that
forms intermediate VI promotes the reaction, whereas
the interaction between the copper salt and the oxygen
atom of the substrate that forms intermediate VII hinders
the reaction.
It is known that alcohols are more nucleophilic than
phenols but have lower acidity than phenols. The interac-
tion between the oxygen atom of alcohol with copper
salt (VII) that decreases the nucleophilicity of alcohol

DONG ET AL.
9 of 10
formyl cyanide intermediates, and forming phenolic salts,
which enable the high efficiency of the reaction without
the assistance of any of the acids, bases, and ligands,
which are rarely reported and attractive in copper
chemistry.
(2.0 mmol, 234 mg) and alcohol 2a (10 ml) was added at
room temperature. Then, the Schlenk tube was sealed,
and the reaction mixture was stirred at 120ꢀC for 24 h.
After completion of the reaction, the resulting solution
was cooled to room temperature and neutralized with
saturated NH4Cl solution. The product was extracted
with EtOAc, dried with anhydrous Na2SO4, subject to fil-
tration, and concentrated in vacuo. The residue was puri-
fied by column chromatography on silica gel and eluted
with petroleum ether to afford the desired colorless oil
product ethyl benzoate 3a (240 mg, 80%).
4 | EXPERIMENTAL
4.1 | General information
The reactions were carried out in Schlenk tubes of 25 ml
under the O2 atmosphere. Reagents were used as received
unless otherwise noted, and solvents were purified
according to standard operating procedure. Column chro-
matography was performed using Silica Gel 60 (300–400
mesh). The reactions were monitored by GC and GC–
MS, GC–MS results were recorded on GC–MS QP2010,
and GC analysis was performed on GC 2014 plus. The 1H
and 13C NMR spectra were recorded on a Brucker
ADVANCE III spectrometer at 400 and 101 MHz, respec-
tively, and chemical shifts were reported in parts per mil-
lion (ppm). All solvents and reagents were purchased
from Energy Chemical, Alfa Aesar, and Aladdin.
ACKNOWLEDGMENTS
Financial support from the National Natural Science
Foundation of China (Grant Nos. 21706058, 21878072,
and 21573065), the Hunan Provincial Natural Science
Foundation of China (Grant No. 2020JJ2011), and the
Research Foundation of Education Bureau of Hunan
Province (16B054) is much appreciated. We also thank
Prof. Shuanglin Qu (Hunan University) for his kind help.
AUTHOR CONTRIBUTIONS
Jianyu Dong: Conceptualization; data curation; formal
analysis; funding acquisition; methodology; project
administration; resources; supervision. Xiuling Chen:
Data curation; formal analysis; methodology. Fangyan
Ji: Data curation; formal analysis; methodology. Lixin
Liu: Data curation; methodology. Lebin Su: Data
curation; methodology. Min Mo: Data curation; formal
analysis; funding acquisition. Jian-Sheng Tang: Formal
analysis; methodology. Yongbo Zhou: Data curation;
formal analysis; funding acquisition; investigation;
project administration; resources; supervision.
4.2 | General procedure for the synthesis
of esters 3
An oven-dried 25-ml Schlenk tube, equipped with a mag-
netic stir bar and charged with Cu catalyst, was evacu-
ated and backfilled with O2 three times. Under an oxygen
atmosphere, nitrile 1 (0.2 mmol), alcohol or phenol
2 (0.24 mmol), and CH3CN (1.0 ml) were added at room
temperature. Then, the Schlenck tube was sealed, and
the reaction mixture was stirred at 120ꢀC for 24 h. The
reaction was monitored by GC or GC–MS. After comple-
tion of the reaction, the resulting solution was cooled to
room temperature and neutralized with saturated NH4Cl
solution. The product was extracted with EtOAc, dried
with anhydrous Na2SO4, subject to filtration, and concen-
trated in vacuo. The residue was purified by column
chromatography on silica gel and eluted with petroleum/
ethyl acetate to afford the desired product 3.
DATA AVAILABILITY STATEMENT
The data that supports the findings of this study are avail-
able in the supplementary material of this article.
ORCID
Jianyu Dong https://orcid.org/0000-0003-2161-1372
Yongbo Zhou https://orcid.org/0000-0002-3540-8618
REFERENCES
[1] a) R. C. Larock, Comprehensive Organic Transformations, VCH
1989 966; b) J. Otera, Esterification: Methods, Reactions, and
Applications, Wiley-VCH 2003; c) J. Otera, Chem. Rev. 1993,
93, 1449. and references therein
[2] a) K. C. K. Swamy, N. N. B. Kumar, E. Balaraman, K. V. P. P.
Kumar, Chem. Rev. 2009, 109, 2551; b) S. Verma, R. B. N. Baig,
C. Han, M. N. Nadagouda, R. S. Varma, Green Chem. 2016,
18, 251.
4.3 | Preparation of ethyl benzoate 3a at
2-mmol scale
An oven-dried 100-ml Schlenk tube, equipped with a
magnetic stir bar and charged with CuCl (2 mmol,
198 mg), was evacuated and backfilled with O2 three
times. Under oxygen atmosphere, arylacetonitrile 1a
[3] a) R. C. Larock, Comprehensive Organic Transformations: A
Guide to Functional Group Preparations, 2nd ed., Wiley-VCH

10 of 10
DONG ET AL.
1999; b) K. Ishihara, Tetrahedron 2009, 65, 1085. c) K. Gondo,
Gou, B.-Q. Wang, Z.-J. Shi, Chem. Soc. Rev. 2018, 47, 7078; d)
G. Fumagalli, S. Stanton, J. F. Bower, Chem. Rev. 2017, 117,
9404; e) B.-L. Lu, L. Dai, M. Shi, Chem. Soc. Rev. 2012, 41,
3318; f) L. Souillart, N. Cramer, Chem. Rev. 2015, 115, 9410; g)
M. Rubin, M. Rubina, V. Gevorgyan, Chem. Rev. 2007, 107,
3117. hF. Chen, T. Wang, N. Jiao, Chem. Rev. 2014, 114, 8613.
J. Oyamada, T. Kitamura, Org. Lett. 2015, 17, 4778.
[4] Z. Liu, Q. Ma, Y. Liu, Q. Wang, Org. Lett. 2014, 16, 236.
[5] a) S. A. Ruider, N. Maulide, Angew. Chem., Int. Ed. 2015, 54,
13856; b) L. Hie, N. F. F. Nathel, T. K. Shah, E. L. Baker, X.
Hong, Y. F. Yang, P. Liu, K. N. Houk, N. K. Garg, Nature
2015, 524, 79; c) H. Wu, W. Guo, S. Daniel, Y. Li, C. Liu, Z.
Zeng, Chem. – Eur. J. 2018, 24, 3444; d) Y. Bourne-Branchu, C.
Gosmini, G. Danoun, Chem. – Eur. J. 2017, 23, 10043.
[6] a) T. Ohshima, T. Iwasaki, Y. Maegawa, A. Yoshiyama, K.
Mashima, J. Am. Chem. Soc. 2008, 130, 2944; b) M. Tamura,
S. M. A. H. Siddiki, K. Shimizu, Green Chem. 2013, 15, 1641; c)
J. M. W. Chan, H. Sardon, A. C. Engler, J. M. García, J. L.
Hedrick, ACS Macro Lett. 2013, 2, 860; d) B. Ren, J. Ge, H.
Dong, Green Chem. 2018, 20, 2395; e) S. Prabhakar, T. Vivès,
V. Ferrières, T. Benvegnu, L. Legentil, L. Lemiègre, Green
Chem. 2017, 19, 987; f) C. Zhang, G. Zhang, S. Luo, C. Wang,
H. Li, Org. Biomol. Chem. 2018, 16, 8467.
[7] a) R. Gopinath, B. K. Patel, Org. Lett. 2000, 2, 577; b) R. Tank,
U. Pathak, M. Vimal, S. Bhattacharyya, L. K. Pandey, Green
Chem. 2011, 13, 3350; c) G. Pandey, S. Koley, R. Talukdar,
P. K. Sahani, Org. Lett. 2018, 20, 5861; d) S. Gaspa, A.
Porcheddu, L. De Luca, Org. Lett. 2015, 17, 3666; e) H. Liu,
M. S. Eisen, Eur. J. Org. Chem. 2017, 4852; f) S. Chun, Y. K.
Chung, Org. Lett. 2017, 19, 3787.
[8] a) Z. Wang, Y. Li, F. Zhu, X.-F. Wu, Adv. Synth. Catal. 2016,
358, 2855; b) D. Li, M. Yu, J. Zhang, Z. Liu, Y. Zhang, Org.
Lett. 2015, 17, 5300; c) S. K. Rout, S. Guin, W. Ali, A. Gogoi,
B. K. Patel, Org. Lett. 2014, 16, 3086; d) J. Feng, S. Liang, S. Y.
Chen, J. Zhang, S. S. Fu, X. Q. Yu, Adv. Synth. Catal. 2012,
354, 1287; e) S. K. Rout, S. Guin, A. Banerjee, N. Khatun, A.
Gogoi, B. K. Patel, Org. Lett. 2013, 15, 4106; f) Y.-X. Zhou,
Y.-Z. Chen, L. Cao, J. Lu, H.-L. Jiang, Chem. Commun. 2015,
51, 8292.
[12] A few elegant protocols for construction of esters via C
C
bond cleavage have been reported, see: a) A. Kawata, K.
Takata, Y. Kuninobu, K. Takai, Angew. Chem., Int. Ed. 2007,
46, 7793; b) C. Zhang, P. Feng, N. Jiao, J. Am. Chem. Soc. 2013,
135, 15257; c) H. Liu, C. Dong, Z. Zhang, P. Wu, X. Jiang,
Angew. Chem., Int. Ed. 2012, 51, 12570; d) M. Yu, W. Wen, Z.
Wang, Synth. Commun. 2006, 36, 2851; e) Z. Wang, J. Kang,
M. Yu, J. Chem. Res. 2007, 323; f) W. Kong, B. Li, X. Xu, Q.
Song, J. Org. Chem. 2016, 81, 8436.
[13] a) J. Tsuji, Palladium Reagents and Catalysts: New Perspectives
for the 21st Century, Wiley 2004; b) L. F. Tietze, H. Ha, H. P.
Bell, Chem. Rev. 2004, 104, 3453; c) K. C. Nicolaou, P. G. Bulger,
D. Sarlah, Angew. Chem., Int. Ed. 2005, 44, 4442; d) T. Tlaar, E.
Ruijter, R. V. A. Orru, Adv. Synth. Catal. 2011, 353, 809.
[14] Recent reviews, books, and references therein, see: a) S. Itoh,
S. Fukuzumi, Acc. Chem. Res. 2007, 40, 592; b) S. E. Allen,
R. R. Walvoord, R. Padilla-Salinas, M. C. Kozlowski, Chem.
Rev. 2013, 113, 6234; c) Z. Huang, J.-P. Lumb, ACS Catal.
2019, 9, 521; d) Q. Liu, R. Jackstell, M. Beller, Angew. Chem.,
Int. Ed. 2013, 52, 13871; e) D.-G. Yu, F. de Azambuja, F.
Glorius, Angew. Chem., Int. Ed. 2014, 53, 7710; f) N. Krause,
Modern Organocopper Chemistry, Wiley-VCH 2002.
[15] a) J. Zhu, H. Bienaymé (Eds), Multicomponent Reactions,
Wiley 2005; b) W. Qian, H. Wang, J. Allen, Angew. Chem., Int.
Ed. 2013, 52, 10992. and references therein
[16] a) Q. Michaudel, D. Thevenet, P. S. Baran, J. Am. Chem. Soc.
2012, 134, 2547; b) J. J. Ritter, P. P. Minieri, J. Am. Chem. Soc.
1948, 70, 4048; c) D. Jiang, T. He, L. Ma, Z. Wang, RSC Adv.
2014, 4, 64936; d) K. Kiyokawa, K. Takemoto, S. Minakata,
Chem. Commun. 2016, 52, 13082; e) J.-L. Shi, J.-C. Zhang, B.-Q.
Wang, P. Hu, K.-Q. Zhao, Z.-J. Shi, Org. Lett. 2016, 18, 1238.
[17] For the interaction between copper and the carbonyl groups,
see: a) S. H. Bertz, R. A. Hardin, M. D. Murphy and C. A.
Ogle, Chem. Commun. 2013, 49, 3010; b) J. Jover, Chem. Chem.
Phys. 2017, 19, 29344; c) N. Su, J. A. Theorell, D. J. Wink, T. G.
Driver, Angew. Chem., Int. Ed. 2015, 54, 12942.
[9] a) C. Cai, N. R. Rivera, J. Balsells, R. R. Sidler, J. C.
McWilliams, C. S. Shultz, Y. Sun, Org. Lett. 2006, 8, 5161; b)
M. V. Khedkar, T. Sasaki, B. M. Bhanage, ACS Catal. 2013, 3,
287; c) Y. Tu, L. Yuan, T. Wang, C. Wang, J. Ke, J. Zhao,
J. Org. Chem. 2017, 82, 4970; d) M. Chen, Z.-H. Ren, Y.-Y.
Wang, Z.-H. Guan, J. Org. Chem. 2015, 80, 1258; e) F. Zhu,
X.-F. Wu, Org. Lett. 2018, 20, 3422; f) Y. Li, Z. Wang, X.-F. Wu,
Green Chem. 2018, 20, 969; g) G. Liao, H.-M. Chen, B.-F. Shi,
Chem. Commun. 2018, 54, 10859; h) G. Liao, X.-S. Yin, K.
Chen, Q. Zhang, S.-Q. Zhang, B.-F. Shi, Nat. Commun. 2016,
7, 12901.
[18] Y. Zhang, J. Dong, L. Liu, L. Liu, Y. Zhou, S.-F. Yin, Org. Bio-
mol. Chem. 2017, 15, 2897.
[10] a) L. Su, T. Ren, J. Dong, L. Liu, S. Xie, L. Yuan, Y. Zhou, S.-F.
Yin, J. Am. Chem. Soc. 2019, 141, 2535; b) L. Liu, L.-W. Qian,
S. Wu, J. Dong, Q. Xu, Y. Zhou, S.-F. Yin, Org. Lett. 2017, 19,
2849; c) L. Su, K. Sun, N. Pan, L. Liu, M. Sun, J. Dong, Y.
Zhou, S.-F. Yin, Org. Lett. 2018, 20, 3399; d) L. Su, J. Dong, L.
Liu, M. Sun, R. Qiu, Y. Zhou, S.-F. Yin, J. Am. Chem. Soc.
2016, 138, 12348; e) L. Liu, J. Dong, Y. Zhang, Y. Zhou, S.-F.
Yin, Org. Biomol. Chem. 2015, 13, 9948.
SUPPORTING INFORMATION
Additional supporting information may be found online
in the Supporting Information section at the end of this
article.
How to cite this article: Dong J, Chen X, Ji F,
et al. Copper-mediated simple and direct aerobic
oxidative esterification of arylacetonitriles with
alcohols/phenols. Appl Organomet Chem. 2020;
e6073. https://doi.org/10.1002/aoc.6073
[11] Chemical transformations via
C C bond cleavage have
received much attention, because new skeletons can be
directly constructed from easily available starting materials by
the strategy. For reviews on
C C bond cleavage, see:
a) C.-H. Jun, Chem. Soc. Rev. 2004, 33, 610; b) Y. J. Park, J.-W.
Park, C.-H. Jun, Acc. Chem. Res. 2008, 41, 222; c) F. Song, T.