Electrochemical Dimethyl Sulfide-Mediated Esterification of Amino Acids

Article abstract of DOI:10.1002/cjoc.202100395

Dimethyl sulfide-mediated electrochemical synthetic strategy for esterification of amino acids has been reported. A series of amino acids could react smoothly with alcohols, affording the desired esterification products with good efficiency. Importantly, the tolerance of peptides and gram-scale synthesis shed light on the utility of this protocol. Mechanistically, the dimethyl sulfide as a mediator plays an essential role in the transformation of amino acids.

Full text of DOI:10.1002/cjoc.202100395

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Title: Electrochemical DMS-Mediated Esterification of Amino Acids
Authors: Yongli Li, Huamin Wang, Heng Zhang*, and Aiwen Lei*
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Cite this paper: Chin. J. Chem. 2021, 39, XXX—XXX. DOI: 10.1002/cjoc.202100XXX
Electrochemical DMS-Mediated Esterification of Amino Acids
Yongli Lia, Huamin Wanga, Heng Zhanga*, and Aiwen Leia,b
*
a College of Chemistry and Molecular Sciences, The Institute for Advanced Studies (IAS), Wuhan University, Wuhan 430072, P. R. China
b National Research Center for Carbohydrate Synthesis, Jiangxi Normal University, Nanchang 330022, Jiangxi, P. R. China
Keywords
Organic electrosynthesis | Amino acids | Dimethyl sulfide | Oxidation | Gram scale synthesis
Main observation and conclusion
DMS-mediated electrochemical synthetic strategy for esterification of amino acids has been reported. A series of amino acids could
react smoothly with alcohols, affording the desired esterification products with good efficiency. Importantly, the tolerance of peptides
and gram-scale synthesis shed light on the ultility of this protocol. Mechanistically, the DMS as a mediator plays an essential role in the
transformation of amino acids.
Comprehensive Graphic Content
DMS-mediated activation
amino acids towards
of
esterification
R1
R1
current
constant
OH
R3
O
O
O
+
R2
N
n
OH
R2
N
R3
n
H
H
DMS
O
O
O
examples
Selective
H
N
O
O
O
O
NH
O
O
HN
O
3g
3j
64%
,
92%
,
O
H
O
N
O
O
Gram-scale
N
synthesis
O
O
O
H
NH HN
O
O
3m
3n
70%
,
80%
,
*E-mail: aiwenlei@whu.edu.cn
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&
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First author et al.
Report
Concept for the DMS-mediated activation of amino acids
Background and Originality Content
DMS
-e-
Anode
alcohol
Organic electrosynthesis, by employing electricity as the driving
force for the chemical transformation, has proven to be a powerful
tool for the construction of molecules.[1] In this regard, the cooper-
ation of organic mediator or metal complex with anodic electro-
chemistry has been attracting increasing interest in synthetic chem-
istry.[2] Among them, the combination of anodic electrochemistry
with noble metals, such as rhodium,[2a] ruthenium[2b,2c] and palla-
dium[2d] has been successfully disclosed to generate the target-ori-
ented molecules. In addition, Cheap metals such as copper,[2e] co-
balt,[2f,2g] nickel,[2h] manganese[2i,2j] and iron[2k] have also been well
reported by Mei, Ackermann, Xu, Lin and our group. On the other
hand, the cooperation of organic mediator with anodic electro-
chemistry has also gained much attention as a promising synthetic
platform recently.[3] For instance, the work of Xu group showed a
scalable electrocatalytic 1,2-diamination reaction with the use of
triarylamine as catalyst.[3a] Moreover, Baran and co-workers also re-
ported a Cl4NHPI-catalyzed complex allyl C-H bonds oxygenation via
organic electrochemistry in 2016.[3g] Additionally, Zeng and co-
workers reported TPBA-mediated electrochemical cross-coupling of
phenol and naphthol.[3i] As described above, the combination of
catalysts or mediators with anodic electrochemistry has opened up
powerful strategies for construction of valuable molecules. Though
great success has been made, new mediators need to be exploited
for the combination with anodic electrochemistry, and which is still
attractive yet challenging.
Amino acids, as the basic units of protein, are extremely im-
portant molecules.[4] Hence, the research of amino acids in chemi-
cal transformation has always maintained a high attractiveness. A
variety of methods has been described for the transformation of
these class compounds, providing valuable information for the
study of human life activities,[4d-4f] whereas electrochemistry ena-
bles esterification of the amino acids remains underdeveloped.
Electricity has proven to be a good alternative to oxidants in syn-
thetic chemistry, providing more options for the transformation and
construction of the important molecules. In the research of biolog-
ical and pharmaceutical, the removal of metals result in the compli-
cation of the synthesis process, leading to the waste of resources
and the increase in process costs.[5] From the perspective of syn-
thetic chemistry, the combination of organic mediator and electro-
chemistry would address the challenge of metal residue, offering a
concise and feasible strategy in the drug synthesis. On the other
hand, DMSO, serving as an important organic mediator, has at-
tracted much attention owing to its unique properties over the past
decade, and the Jiao group has made great contribution in this re-
gard.[6] In comparison with DMSO, DMS as mediator has rarely been
reported in synthetic chemistry. Hence, there are great room for the
development of DMS as mediator, especially in the cooperation of
DMS with anodic electrochemistry in organic chemistry.
acid
acid
DMS
acid
DMS
acid
alcohol
Anode
-e-
intermediate I
intermediate II
sensitive to nucleophiles
work:
This
activation
amino acids towards
DMS-mediated
R1
of
esterification
R1
DMS
OH
R3 OH
O
+
R2
N
n
R2
N
R3
n
H
H
O
O
Figure 1 DMS-mediated activation of amino acids towards esterification
through electrochemical oxidation.
Results and Discussion
Table 1. Optimization of the reaction conditionsa
C
I Pt
25 mA,
7 h
(+)
DMS
(-),
(2.5 equiv.)
O
nBu4NBF
rt, N
O
mol%),
4 (20
2
OH
O
CH3OH
O
N
O
N
H
CH CN mL)
(8
H
3
O
O
1a
2a
3a
Entry
Variation from the standard conditions
Yield(%)[b]
none
1
82
2
CH CN mL)
(5
67
3
3
4
CH CN
3
mL)
80
54
73
80
(10
CH OH
(1.0 equiv.)
(3.0 equiv.)
(5.0 equiv.)
3
5
CH OH
3
6
CH OH
3
7
dimethyl
67
trace
63
sulfide
(1.5 equiv.)
8
without dimethyl sulfide
nBu4NPF6
9
nBu4NCl
10
41
11
12
13
14
15
16
C
C
I C
12
48
70
80
(+)
(-)
(-)
I Ni
mA
mA
(+)
20
30
air
electricity
73
no
n.d.
aReaction conditions : N-Carbobenzyloxyglycine (1a, 0.6 mmol), CH3OH (2a,
100 μL), nBu4NBF4 (0.2 equiv.), dimethyl sulfide (2.5 equiv.), and CH3CN (8
mL) in an undivided cell with carbon electrode anode, platinum cathode,
1
constant current = 25 mA, rt, 7 h. [b] Yields were determined by H NMR
Based on recent report from our group on the electrochemcial
oxidation strategy,[7] we hypothesised whether such a strategy
could be used to activate the amino acids with the use of DMS as
mediator with the help of anodic electrochemistry (Figure 1). If
successful, acids would transform into an intermediate I which
contains sulfide unit, followed by the oxidation of sulfur atom could
form an activative intermediate II, which is sensitive to nucleophilic
substances. Subsequently, alcohols as nucleophlies to attack the
compound II to form the desired product. Herein, a DMS-mediated
electrochemical oxidation strategy for activation of amino acids is
reported. A series of amino acids could react successfully with pri-
mary and secondary alcohols, furnishing the desired amino acid es-
ters with good efficiency. Importantly, the tolerance of peptides and
gram-scale synthesis demonstrate the potential application of this
protocol in industrial chemistry. Mechanistically, the DMS as a me-
diator plays an essential role in the transformation of amino acids
with the use of dibromomethane as internal standard.
Initially, we chose N-Carbobenzyloxyglycine (1a) and CH3OH (2a)
as the reaction partners to optimize the conditions (Table 1). The
amount of the CH3CN has an influence on the yield of 3a. Changing
the amount of the alcohol has no obvious effect on the reaction
yield (entries 4-6). It is worthy mentioning that there is only trace
amount of esterification products without DMS (dimethyl sulfide),
suggesting that DMS is critical in this transformation (entry 8).
n
Moreover, the yield decreased when we replaced the Bu4NBF4 to
n
nBu4NPF6 or Bu4NCl (entries 9 and 10). Further screening of the
materials of electrodes shows that the conditions with carbon rode
anode and platinum cathode was optimal (entries 11 and 12). To
our delight, this reaction proceed smoothly at air atmosphere. Last
but not least, no desired products was oserved in the absence of
electricity, demonstrating the essential role of electricity in this
activation of amino acids (entry 16).
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Chin. J. Chem. 2021, 39, XXX－XXX

Running title
Chin. J. Chem.
Investigation of various mediators
To further investigate the effect of DMS in this electrochemical
protocol, a series of sulfide derivatives as a baton were examined,
as shown in Figure 2. The reaction could proceed smoothly with
moderate to high yields with various aliphatic sulfides as additives.
It is worth mentioning that aromatic sulfides offered desired prod-
uct with lower yield compared with the aliphatic sulfides, which
might because that aliphatic sulfides reacted more efficiently with
amino acids. Hence, DMS was chosen as the optimal baton for the
activation of amino acids owing to the high efficiency and the ad-
vantage of economy.
C
I Pt
25 mA,
7 h
(+)
(-),
(2.5 equiv.)
rt, N
mediators
O
nBu4NBF
O
mol%),
4 (20
2
OH
O
CH3OH
O
N
O
N
H
CH CN mL)
(8
H
3
O
O
1a
sulfide
2a
3a
Aromatic sulfide
Aliphatic
S
Cl
S
S
S
57%
61%
35%
40%
32%
S
S
N
S
S
50%
73%
77%
Figure 2 Investigation of various sulfides as mediators.
condition A
condition B
R1
R1
OH
O
or
R3
n
n
N
R2
N
R2
R3OH
O
O
DMS
1
2
3
Amino acid derivatives
O
O
O
O
O
O
O
O
O
O
N
O
N
O
H
H
N
H
O
O
O
3d
N
H
O
O
O
3a
,
3b
3c
84%
,
82%
94%
O
92%
,
,
O
O
OH
O
O
O
O
NH
HN
O
O
HN
O
O
O
N
H
O
O
O
O
3e
,
3f
3g
3h
80%
,
90%
70%
O
92%
,
,
O
O
H
O
O
N
O
O
O
O
O
O
O
NH
N
O
O
O
O
N
H
S
O
O
O
HN
O
O
3i
3j
3k
,
3l
84%
,
60%
64%
80%
,
,
derivatives
Dipeptide
H
N
O
O
H
O
O
O
N
O
N
O
O
O
O
O
H
O
N
H
NH HN
O
O
O
3m
3n
3o
,
80%
70%
81%
,
,
Alcohols
O
O
O
H
O
O
H
H
N
H
N
O
N
N
O
O
O
O
O
O
O
O
O
O
F
3p
3q
3r
3s 72%
,
60%
O
52%
50%
,
,
,
O
O
O
O
H
H
H
N
H
O
N
O
O
N
Cl
O
O
N
O
O
O
O
O
O
O
O
O
3t
3u 77%
,
3v 55%
,
3w
53%
,
51%
,
O
O
O
H
H
H
N
O
O
N
O
N
O
O
O
O
S
O
O
O
O
3x
,
3y
,
3z
50%
,
70%
61%
Figure 3 Substrates Scope. a Condition A respect to amino acids: amino acid (1, 0.6 mmol), CH3OH (2a, 100 μL), nBu4NBF4 (0.2 equiv.), dimethyl sulfide (2.5
equiv.), and CH3CN (8 mL), constant current = 25 mA, rt, 7 h. Condition B respect to alcohols: N-Carbobenzyloxyglycine (1a, 0.6 mmol), alcohol (2, 4.0 equiv.),
nBu4NBF4 (0.2 equiv.), dimethyl sulfide (3.0 equiv.), and CH3CN (8 mL), constant current = 30 mA, rt, 7 h.
With the optimal conditions in hand, the substrate scope was
evaluated with the use of DMS (dimethyl sulfide) as mediator
(Figure 3). Firstly, various amino acids were investigated. As is
shown in Figure 3, N-Cbz-alanine and N-Cbz-phenylalanine could
Chin. J. Chem. 2021, 39, XXX－XXX
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First author et al.
Report
react smoothly with CH3OH with the help of DMS under
electrochemcial conditions (3b and 3h). Moreover, aspartic acid
derivatives, such as 4-cyclohexyl ester and N-Cbz-aspartic acid 4-
methyl ester could also affored desired esterification products in
good yield (3c and 3k). When we used N-Cbz-isoleucine (3d) and
leucine (3f) as reaction partners, 92% yield and 70% yield were
obatined respectively. Importantly, this protocol was compatible
with compounds which contain hydroxyl group (3e), successfully
offered the desired product in 90% yield. Nateglinide (3g), always
serving as an efficient drug for diabetes, was well tolerated. In
addition, β-amino acid was successfully used to access the product
of esterification (3l). Gratifyingly, 2,5-bis(((benzyloxy)carbonyl)-
amino)pentanoic acid was smoothly transformed to desired
product in 64% yield (3j). It is worth mentioning that peptides could
be well tolerated in this DMS-mediated esterification strategy,
furnishing desired products in good yields (3m-3o).
Subsequently, we examined the substrate scope of the alcohols.
alkyl chloride, that is sensitive to nucleophilic substitution, could
react smoothly to generate the desired product (3u). Chain and
cyclic ether compounds, which are oxidatively labile groups, were
amenable to this electrochemcial esterification protocol (3t, 3v and
3w). Secondary alcohols were also found to be suitable reaction
partners (3v and 3y). Furthermore, sufonyl groups were also well
tolerated (3z). These above results highlighted good functional
group tolerance of this protocol.
Mechanistic studies
Intermediate
experiment
A)
O
O
C
I Pt
25 mA, 5 h
(-),
(+)
nBu4NBF
O
S
O
rt
4 (20%),
O
N
H
O
N
+
CH3OH
H
O
O
CH3CN mL)
(8
4a
2a
3a 55%
,
Control
experiment
B)
O
O
nBu4NBF
rt, 5 h
O
S
O
4 (20%),
O
N
H
O
N
H
+
CH3OH
CH3CN mL)
(8
O
O
n.d.
4a
2a
3a
,
In-situ IR
experiment
C)
DMS
O
O
C
O
I Pt
25 mA, 8 h
(-),
(+)
nBu4NBF
OH
O
rt
4 (20%),
O
N
O
N
+
CH3OH
H
H
O
O
CH3CN
mL)
(16
O
3a
1a
O
S
N
H
4a
O
intermediate
1a
4a
1a
4a
4a
3a
Time
To get an investigation of the mechanism of this electrochemi-
cal protocol, control experiments were performed (Figure 4). 4a,
which was detected by GC-MS during the reaction, could react
smoothly with CH3OH to forge the desired product 3a with 55%
yield, suggesting that 4a might be an intermediate of this transfor-
mation (Figure 4A). On the other hand, no desired product was ob-
served with 4a as starting materials in the absence of electricity,
which means that electricity is essential for the further transfor-
mation of 4a to desired product (Figure 4B).
To know more details about the mechanism, in situ-IR was car-
ried out to monitor this reaction (Figure 4C). The characteristic
peaks of 3a and 4a are at 1210 cm-1 and 1172cm-1. As is shown, 4a
was produced with the assumption of N-Cbz-glycine (1a), which fur-
ther reveal that 4a might be the intermediate in this DMS-mediated
electrochemical esterification. Subsequently, esterification product
(3a) was generated through the observation of in situ-IR, at the
same time 4a is rapidly consumed. Moreover, the cyclic voltamme-
try (CV) experiments were per-formed to know details about the
reaction. Compared with the N-Cbz-glycine (1a) and intermediate
(4a), the DMS (dimethyl sulfide) can be quickly oxidized under the
electrochemical conditions, which first promotes the activation of
N-Cbz-glycine (1a) through its reaction with the DMS.
Figure 4 Mechanistic studies.
Anode
Cathode
O
O
O
OH
S
O
N
O
O
N
H
H
3a
CH3OH
+e-
O
O
O
-e-
DMSO
CH3O-
O
O
S
O
N
H
O
S
O
N
H
4a
O
III
-e-
O
O
-H+
-e-
O
S
O
S
O
N
H
O
N
H
O
O
II
I
Figure 5 Proposed mechanism.
C
I Pt
30 mA, 50 h
(-),
(+)
DMS
(2.5 equiv.)
mol%),
O
nBu4NBF
rt, N
2
O
Based on the experiments above, we proposed a mechanism of
this DMS-mediated electrochemical esterification, which is shown
in Figure 5. Firstly, the amino acid is activated to form intermediate
4a through the reaction with DMS (dimethyl sulphide). Dimethyl
sulphide as a baton is crucial for this transformation. Then, 4a is
oxidized to afford compound I through the electron transfer (ET) at
the anode. Intermediate II, which rearrange from intermediate I, is
reduced to III through the ET at cathode. Furthermore, CH3OH is
reduced to CH3O- at the cathode along with the release of H2. Finally,
the desired product is obtained by the substitution of CH3O-.
To further evaluate the utility of this DMS-mediated protocol, the
larger scale synthesis was performed (Figure 6). Pleasingly, 73%
yield could be obtained when 9 mmol 1a was used as reaction sub-
strate.
4 (20
OH
O
CH3OH
O
N
O
N
CH CN
mL)
(100
3
H
H
O
O
mmol
mL
9
1.5
73%
Figure 6 Gram-scale synthesis.
Conclusions
In conclusion, we have disclosed an electrochemical oxidation
strategy for activation of amino acids with the use of DMS as medi-
ator. A series of amino acids could react smoothly with alcohols,
affording the desired esterification products with good efficiency.
Importantly, the tolerance of peptides and gram-scale synthesis
further demonstrats the ultility of this protocol. Mechanistic stud-
ies reveal the DMS as a mediator plays an essential role in the trans-
formation of amino acids, which not only promotes the
esterification of amino acids but also offer a way for the research
of amino acids in synthetic chemistry. Ongoing researches including
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Running title
Chin. J. Chem.
further mechanism and scopes are currently underway.
(d) Yang, Q.-L.; Li, Y.-Q.; Ma, C.; Fang, P.; Zhang, X.-J.; Mei, T.-S. Palla-
dium-Catalyzed C(sp3)-H Oxygenation via Electrochemical Oxidation. J.
Am. Chem. Soc. 2017, 139, 3293−3298; (e) Yang, Q. L.; Wang, X. Y.; Lu,
J. Y.; Zhang, L. P.; Fang, P.; Mei, T. S. Copper-Catalyzed Electrochemical
C-H Amination of Arenes with Secondary Amines. J. Am. Chem. Soc.
2018, 140, 11487−11494. (f) Gao, X.; Wang, P.; Zeng, L.; Tang, S.; Lei,
A. Cobalt(II)-Catalyzed Electrooxidative C-H Amination of Arenes with
Alkylamines. J. Am. Chem. Soc. 2018, 140, 4195−4199; (g) Sauermann,
N.; Meyer, T. H.; Tian, C.; Ackermann, L. Electrochemical Cobalt-Cata-
lyzed C-H Oxygenation at Room Temperature. J. Am. Chem. Soc. 2017,
139, 18452−18455; (h) Qiu, H.; Shuai, B.; Wang, Y.-Z.; Liu, D.; Chen, Y.-
G.; Gao, P.-S.; Ma, H.-X.; Chen, S.; T.-S. Mei. Enantioselective Ni-Cata-
lyzed Electrochemical Synthesis of Biaryl Atropisomers. J. Am. Chem.
Soc. 2020, 142, 9872–9878; (i) Fu, N. K.; Sauer, G. S.; Saha, A.; Loo, A.;
Lin, S. Metal-catalyzed electrochemical diazidation of alkenes. Science
2017, 357, 575–579; (j) Fu, N. K.; Sauer, G. S.; Lin, S. Electrocatalytic
Radical Dichlorination of Alkenes with Nucleophilic Chlorine Sources. J.
Am. Chem. Soc. 2017, 139, 15548−15553; (k) Xiong, P.; Xu, H.-H.; Song,
J. S.; Xu, H.-C. Electrochemical Difluoromethylarylation of Alkynes. J.
Am. Chem. Soc. 2018, 140, 2460–2464.
Experimental
A mixture of amino acid (0.6 mmol), dimethyl sulfide (3.0
equiv.), alcohol (4 equiv.) or CH3OH (100 uL), nBu4NBF4 (0.2 equiv.),
CH3CN (8 mL), in an undivided cell under nitrogen atmosphere with
carbon electrode anode, plate cathode, constant current = 25 mA,
rt, 7 h. Then, the system was concentrated under reduced pressure.
The resulting crude product was separated on a silica gel column
with petroleum ether and ethyl acetate as eluent to afford the de-
sired product.
Supporting Information
The supporting information for this article is available on the
WWW under https://doi.org/10.1002/cjoc.2021xxxxx.
(a) Cai, C.-Y.; Shu, X.-M.; Xu, H.-C. Practical and stereoselective elec-
trocatalytic 1,2-diamination of alkenes. Nat. Com. 2019, 10, 4953-4960;
(b) Fu, N.; Li, L.; Yang, Q.; Luo, S. Catalytic Asymmetric Electrochemical
Oxidative Coupling of Tertiary Amines with Simple Ketones. Org. Lett.
2017, 19, 2122−2125; (c) Sauermann, N.; Meyer, T. H.; Qiu, Y. A.;
Ackermann, L. Electrocatalytic C−H Activation. ACS Catal. 2018, 8,
7086−7103; (d) Qian, X.-Y.; Li, S.-Q.; Song, J. S.; Xu, H.-C. TEMPO-Cata-
lyzed Electrochemical C−H Thiolation: Synthesis of Benzothiazoles and
Thiazolopyridines from Thioamides. ACS Catal. 2017, 7, 2730−2734; (e)
Zhao, H.-B.; Xu, P.; Song, J. S.; Xu, H.-C. Cathode Material Determines
Product Selectivity for Electrochemical C−H Functionalization of Biaryl
Ketoximes. Angew. Chem. Int. Ed. 2018, 57, 15153 –15156; (f) Hu, K. F.;
Zhang, Y.; Zhou, Z. H.; Yang, Y.; Zha, Z. G.; Wang, Z. Y. Iodine-Mediated
Electrochemical C(sp2)–H Amination: Switchable Synthesis of Indolines
and Indoles. Org. Lett. 2020, 22, 15, 5773–5777; (g) Horn, E. J.; Rosen,
B. R.; Chen, Y.; Tang, J. Z.; Chen, K.; Eastgate, M. D.; Baran, P. S. Scalable
and sustainable electrochemical allylic C–H oxidation. Nature 2016,
533, 77–81; (h) Hou, Z.-W.; Xu, H.-C. Electrochemically Enabled Intra-
molecular Aminooxygenation of Alkynes via Amidyl Radical Cyclization.
Chin. J. Chem. 2020, 38, 394-398; (i) Wang, Q.-Q.; Jiang, Y.-Y.; Zeng, C.-
C.; Sun, B.-G. Electrocatalytic Synthesis of Non-Symmetric Biphenols
Mediated by Tri(p-bromophenyl)amine: Selective Oxidative Cross-
Coupling of Different Phenols and Naphthols. Chin. J. Chem. 2019, 37,
352-358; (j) Zhang, N.-T.; Zeng, C.-C.; Lam, C. M.; Gbur, R. K.; Little, R.
D. Triarylimidazole Redox Catalysts: Electrochemical Analysis and Em-
pirical Correlations. J. Org. Chem. 2013, 78, 2104–2110; (k) Lu, N.-N.;
Yoo, S. J.; Li, L.-J.; Zeng, C.-C.; Little, R. D. A comparative study of or-
ganic electron transfer redox mediators: electron transfer kinetics for
triarylimidazole and triarylamine mediators in the oxidation of 4-meth-
oxybenzyl alcohol. Electrochim. Acta, 2014. 142, 254-260.
(a) Hedges, J. B.; Ryan, K. S. Biosynthetic Pathways to Nonproteino-
genic α-Amino Acids. Chem. Rev. 2020, 120, 3161−3209; (b) Moschner,
J.; Stulberg, V.; Fernandes, R.; Huhmann, S.; Leppkes, J.; Koksch, B. Ap-
proaches to Obtaining Fluorinated α-Amino Acids. Chem. Rev. 2019,
119, 10718−10801; (c) Xie, Y.-P.; Cao, C.-H.; Zheng, Y.-G. Enzymatic
asymmetric synthesis of chiral amino acids. Chem. Soc. Rev. 2018, 47,
1516-1561; (d) Yan, T.; Feringa, B. L.; Barta, K. Direct N-alkylation of
unprotected amino acids with alcohols. Sci. Adv. 2017, 3: eaao6494; (e)
Glachet, T.; Marzag, H.; Rosa, N. S.; Colell, J. F. P.; Zhang, G. N.; Warren,
W. S.; Franck, X.; Theis, T.; Reboul, V. Iodonitrene in Action: Direct
Transformation of Amino Acids into Terminal Diazirines and 15N2‑Di-
azirines and Their Application as Hyperpolarized Markers. J. Am. Chem.
Soc. 2019, 141, 13689−13696; (f) Leonard, D. J.; Ward, J. W.; Clayden,
J. Asymmetric α-arylation of amino acids. Nature. 2018, 562, 105-111.
(a) Jasperse, C. P.; Curran, D. P.; Fevig, T. L. Radical reactions in natural
product synthesis. Chem. Rev. 1991, 91, 1237–1286; (b) Mandal, S.;
Acknowledgement (optional)
This work was supported by the National Natural Science Foun-
dation of China (22031008) and Science Foundation of Wuhan
(2020010601012192). The Program of Introducing Talents of Disci-
pline to Universities of China (111 Program) is also appreciated.
Dedicated to Prof. Christian Bruneau for his outstanding contribu-
tion to catalysis
References
(a) Amatore, C.; Jutand, A. Anionic Pd(0) and Pd(II) Intermediates in
Palladium-Catalyzed Heck and Cross-Coupling Reactions. Acc. Chem.
Res. 2000, 33, 314-321; (b) Jiang, Y. Y.; Xu, K.; Zeng, C. C. Use of Elec-
trochemistry in the Synthesis of Heterocyclic Structures. Chem. Rev.
2018, 118, 4485-4540; (c) Wang, H. M.; Gao, X. L.; Lv, Z. C.; Abdelilah,
T.; Lei, A. W. Recent Advances in Oxidative R1‑H/R2‑H Cross-Coupling
with Hydrogen Evolution via Photo-/Electrochemistry. Chem. Rev.
2019, 119, 6769-6787. (d) Nutting, J. E.; Rafiee, M.; Stahl, S. S. Tetra-
methylpiperidine N‑Oxyl (TEMPO), Phthalimide N‑Oxyl (PINO), and
Related N‑Oxyl Species: Electrochemical Properties and Their Use in
Electrocatalytic Reactions. Chem. Rev. 2018, 118, 4834−4885; (e) Yo-
shida, J.-I.; Kataoka, K.; Horcajada, R.; Nagaki, A. Modern Strategies in
Electroorganic Synthesis. Chem. Rev. 2008, 108, 2265-2299; (f) Wang,
S. C.; Tang, S.; Lei, A. W. Tuning radical reactivity for selective radi-
cal/radical cross-coupling. Sci. Bull. 2018, 63, 1006-1009. (g) Xiong, P.;
Xu, H.-C. Chemistry with Electrochemically Generated N Centered Rad-
icals. Acc. Chem. Res, 2019, 52, 3339-3350; (h) Yan, M.; Kawamata, Y.;
Baran, P. S. Synthetic Organic Electrochemical Methods Since 2000: On
the Verge of a Renaissance. Chem Rev, 2017, 117, 13230-13319. (i)
Yang, Q.-L.; Fang, P.; Mei, T.-S. Recent Advances in Organic Electro-
chemical C-H Functionalization. Chin. J. Chem. 2018, 36, 338-352. (j)
Qian, P.; Zha, Z. G.; Wang, Z. Y. Recent Advances in C-H Functionaliza-
tion with Electrochemistry and Various Iodine-Containing Reagents.
ChemElectroChem, 2020, 7, 2527-2544. (k) Yu, M.; Shi, W. Y.; Lei, A. W.
Photo/electrochemical oxidation induced C–H bond functionalization.
SCIENTIA SINICA Chimica 2021, 51, 188-200.
(a) Qiu, Y. A.; Scheremetjew, A.; Ackermann, L. Electro-Oxidative C–C
Alkenylation by Rhodium(III) Catalysis. J. Am. Chem. Soc. 2019, 141,
2731-2738; (b) Qiu, Y. A.; Tian, C.; Massignan, L.; Rogge, T.; Ackermann,
L. ElectrooxidativeRuthenium-Catalyzed C-H/O-H Annulation by Weak
O-Coordination. Angew. Chem. Int. Ed. 2018, 57, 5818 –5822; (c) Xu,
F.; Li, Y.-J.; Huang, C.; Xu, H.-C. Ruthenium-Catalyzed Electrochemical
Dehydrogenative Alkyne Annulation. ACS Catal. 2018, 8, 3820−3824;
Chin. J. Chem. 2021, 39, XXX－XXX
© 2021 SIOC, CAS, Shanghai, & WILEY-VCH GmbH
www.cjc.wiley-vch.de

First author et al.
Report
Bera, T.; Dubey, G.; Saha, J.; Laha, J. K. Uses of K2S2O8 in Metal-Cata-
eaaz0590; (c) Liu, K.; Song, C. L.; Jiang, X.; Dong, X.; Deng, Y. Q.; Song,
W, X.; Yang, Y. P.; Lei, A. W. Electrochemical Ring Expansion to Synthe-
size Medium-Sized Lactams Through C–C Bond Cleavage. CCS Chem.
2020, 2, 2233-2244; (d) Liu, Yichang; Yi, Hong; Lei, Aiwen, Oxidation-
Induced CH Functionalization: A Formal Way for CH Activation. Chin. J.
Chem. 2018, 36, 692-697; (e) Liu, Kun; Deng, Yuqi; Song, Wenxu; Song,
Chunlan; Lei, Aiwen, Electrochemical Dearomative Halocyclization of
Tryptamine and Tryptophol Derivatives. Chin. J. Chem. 2020, 38, 1070-
1074.
lyzed and Metal-Free Oxidative Transformations. ACS Catal. 2018, 8,
5085−5144; (c) Iqbal, J.; Bhatia, B.; Nayyar, N. K. Transition Metal-Pro-
moted Free-Radical Reactions in Organic Synthesis: The Formation of
Carbon-Carbon Bonds. Chem. Rev. 1994, 94, 519–564.
(a) Zhu, Y. C.; Zhang, Z. Y.; Jin, R.; Liu, J. Z.; Liu, G. Q.; Han, B.; Jiao, N.
DMSO-Enabled Selective Radical O-H Activation of 1,3(4)-Diols. Angew.
Chem. Int. Ed. 2020, 59, 19851 –19856; (b) Song, S.; Li, X. Y.; Wei, J. L.;
Wang, W. J.; Zhang, Y. Q.; Ai, L. S.; Zhu, Y. C.; Shi, X. M.; Zhang, X. H.;
Jiao, N. DMSO-catalysed late-stage chlorination of (hetero)arenes. Nat.
Cat. 2020, 3, 107-115; (c) Song, S.; Li, X. W.; Sun, X.; Yuan, Y. Z.; Jiao, N.
Efficient bromination of olefins, alkynes, and ketones with dimethyl
sulfoxide and hydrobromic acid. Green Chem., 2015, 17, 3285–3289.
(a) Wang, H. M.; He, M.; Li, Y. L.; Zhang, H.; Yang, D. L.; Nagasaka, M.;
Lv, Z. C.; Guan, Z. P.; Cao, Y. M.; Gong, F. P.; Zhou, Z. L.; Zhu, J. Y.; Sa-
manta, Chowdhury, A. D.; Lei, A. W. Electrochemical Oxidation Enables
Regioselective and Scalable α-C(sp3)-H Acyloxylation of Sulfides. J. Am.
Chem. Soc. 2021, 143, 3628–3637; (b) Wang, H. M.; Liang, K. L.; Xiong,
W. P.; Samanta, S.; Li, W. Q.; Lei, A. W. Electrochemical oxidation-in-
duced etherification via C(sp3)-H/O-H cross coupling. Sci Adv. 2020, 6:
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Chin. J. Chem. 2021, 39, XXX－XXX

Running title
Chin. J. Chem.
Entry for the Table of Contents
Electrochemical DMS-Mediated Esterification of Amino Acids
Yongli Lia, Huamin Wanga, Heng Zhanga*, and Aiwen Leia,b
*
Chin. J. Chem. 2021, 39, XXX—XXX. DOI: 10.1002/cjoc.202100XXX
DMS mediated activation of amino acids
DMS
alcohol
acid
acid
acid
DMS
alcohol
Anode
-e-
Anode
-e-
Cross
substitution
coupling
Nucleophilic
A DMS-mediated esterification of amino acids by electrooxidation has been discovered, which featured simple operation, good functional-groups
tolerance and gram-scale synthesis etc. Crucially, this protocol provides not only methodology for the syntheses of amino acid esters, but also guidelines
for the activation of amino acids.
Chin. J. Chem. 2021, 39, XXX－XXX
© 2021 SIOC, CAS, Shanghai, & WILEY-VCH GmbH
www.cjc.wiley-vch.de