Electrochemical Oxidative Oxydihalogenation of Alkynes for the Synthesis of α,α-Dihaloketones

Article abstract of DOI:10.1021/acs.orglett.0c00052

An electrochemical oxydihalogenation of alkynes has been developed for the first time. Using this sustainable protocol, a variety of α,α-dihaloketones can be prepared with readily available CHCl₃, CH₂Cl₂, ClCH₂CH₂Cl, and CH₂Br₂ as the halogen source under electrochemical conditions at room temperature.

Full text of DOI:10.1021/acs.orglett.0c00052

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Letter
Electrochemical Oxidative Oxydihalogenation of Alkynes for the
Synthesis of α,α-Dihaloketones
Xiangtai Meng, Yu Zhang, Jinyue Luo, Fei Wang, Xiaoji Cao, and Shenlin Huang*
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ABSTRACT: An electrochemical oxydihalogenation of alkynes has been developed for the first time. Using this sustainable
protocol, a variety of α,α-dihaloketones can be prepared with readily available CHCl3, CH2Cl2, ClCH2CH2Cl, and CH2Br2 as the
halogen source under electrochemical conditions at room temperature.
he α,α-dihaloketones belong to important structural
including the use of excess strong oxidants, expensive/toxic
halogenating reagents, high reaction temperature, and low
atom efficiency. Thus, the development of novel and
sustainable approaches for the synthesis of α,α-dihaloketones
from alkynes is still highly desirable.
T
motifs in various pharmaceutical chemicals and natural
products.1 In addition, they are also useful building blocks in
the synthesis of biologically active heterocycles2 and other
germinal dihalo compounds.3 Thus, the development of
practical synthetic methods of α,α-dihaloketones has become
a compelling interest. The transformation of alkynes to the
corresponding dihaloketones is one of the conventional
protocols (Scheme 1a), which often requires the use of
The revival of electrochemical organic synthesis11 has
demonstrated the mildness and sustainability of electro-
chemistry. Compared to traditional oxidative reactions, the
electrochemical protocol does not require the use of toxic or
dangerous oxidants. In particular, electrocatalytic strategies
have been conveniently employed to achieve C−C,12 C−O,13
C−N,14 and C−S15 bond formation reactions. Despite these
advances, electrochemical C−X (Cl or Br) bond formations16
have been rarely reported. Of particular interest to us was a
recent report of alkyne dibromination under electrochemical
conditions (Scheme 1b).16d Encouraged by these reports, we
reported the first electrocatalytic oxydihalogenation of alkynes
using CHCl3, CH2Cl2, ClCH2CH2Cl, and CH2Br2 as the
halogen source and water as the eco-friendly oxygen source17
at room temperature (Scheme 1c).
Scheme 1. Dihalogenation of Alkynes
To experimentally confirm our proposal, we choose
commercially available phenylacetylene 1a as a model substrate
for the oxydichlorination in an undivided cell equipped with
two platinum electrodes. To our delight, the desired 2,2-
dichloroacetophenone 2a was indeed obtained in 89% HPLC
yield when the reaction was conducted under constant current
electrolysis at 10 mA in the presence of tetrabutylammonium
iodide (TBAI, 0.8 equiv), LiClO4 (1.0 equiv), and H2O (2.0
corrosive molecular halogens.4 Over the past decades,
considerable efforts have been devoted to the search for
alternative halogen sources,5 such as NCS,6 NBS,7 trichlor-
oisocyanuric acid (TCCA),8 and 1,3-dibromo-5,5-dimethylhy-
dantoin (DBDMH).9 Recently, oxydihalogenation of alkynes
with halide ions has also been reported,10 although effectively,
these synthetic protocols typically suffer from limitations
Received: January 6, 2020
https://dx.doi.org/10.1021/acs.orglett.0c00052
© XXXX American Chemical Society
Org. Lett. XXXX, XXX, XXX−XXX
A

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a b
,
equiv), in MeCN/CHCl3 (9.2 mL/0.8 mL) at room
temperature (Table 1, entry 1). Attempts to replace a platinum
Scheme 2. Electrochemical Oxydichlorination of Alkynes
a
Table 1. Optimization of Reaction Conditions
b
entry
variation from standard conditions
none
Pt (+) | C (−) instead of Pt (+) | Pt (−)
C (+) | Pt (−) instead of Pt (+) | Pt (−)
NH4I instead of TBAI
KI instead of TBAI
TBAB instead of TBAI
without CHCl3
yield
1
2
3
4
5
6
7
89%
17%
50%
trace
trace
trace
c
n.d.
8
9
CHCl3 instead of CH3CN as the solvent
0.6 equiv TBAI instead of 0.8 equiv TBAI
1.0 equiv TBAI instead of 0.8 equiv TBAI
5 mA instead of 10 mA, 10 h
15 mA instead of 10 mA, 4 h
n-Bu4NBF4 instead of LiClO4
n-Bu4NPF6 instead of LiClO4
without current
trace
84%
62%
50%
72%
trace
trace
n.d.
10
11
12
13
14
15
a
Standard conditions: constant current = 10 mA, 1a (0.3 mmol),
TBAI (0.8 equiv), LiClO4 (1.0 equiv), H2O (2.0 equiv), MeCN/
CHCl3 (10.0 mL, 9.2/0.8) in an undivided cell with two platinum
b
electrodes, rt, 6 h. Yields were determined by HPLC analysis with
c
naphthalene as the internal standard. n.d. = not detected.
electrode with a graphite electrode resulted in a significant
decrease of yields (Table 1, entries 2 and 3). Other additives,
such as NH4I, KI, and tetrabutylammonium bromide (TBAB),
were also examined, and only a trace amount of 2a was
detected on HPLC (Table 1, entries 4−6). Not surprisingly,
no desired product 2a was observed in the absence of CHCl3
(Table 1, entry 7). A reaction run in CHCl3 without MeCN
gave only a trace amount of desired product (Table 1, entry 8).
Lowering or raising the amount of TBAI or the current
reduced the oxydichorination reaction efficiency (Table 1,
entries 9−12). The reaction was dramatically affected upon
replacing the electrolyte with either n-Bu4NBF4 or n-Bu4NPF6
(Table 1, entries 13 and 14). Finally, a control reaction without
electricity was conducted, and no desired product was
observed, confirming the importance of electrocatalysis in
facilitating this transformation (Table 1, entry 15).
Having identified the optimized conditions, we then
explored the substrate scope for this oxydichlorination with a
variety of readily available alkynes. As shown in Scheme 2, this
oxydichlorination tolerates various functional groups and
substitution patterns on the aryl rings. Alkynes bearing
electron-donating groups (Me, t-Bu, MeO) on the phenyl
ring participated in the reaction smoothly to give products 2a−
2f in good to high yields. In addition to para-substituted
phenylacetylenes, meta- and ortho-substituted phenylacetylenes
(2b and 2f) could also work well in this transformation. The
reaction of phenylacetylenes with electron-withdrawing groups
(F, Cl, Br, CHO, CO2Me, CN, NO2) on the benzene ring
proceeded smoothly to deliver the corresponding α,α-
dichloroketones 2g−2n in moderate to good yields. In
addition, the fragile TMS and TBS groups (2o and 2p) were
also compatible in this oxydichlorination. Moreover, internal
a
Standard conditions: constant current = 10 mA, 1a (0.3 mmol),
TBAI (0.8 equiv), LiClO4 (1.0 equiv), H2O (2.0 equiv), and MeCN/
CHCl3 (10.0 mL, 9.2/0.8) in an undivided cell with two platinum
b
electrodes, rt, 6 h. Isolated yield.
alkynes were also good candidates for the oxydichlorination
and rendered the expected α,α-dichloroketones 2q and 2r in
moderate yields. Notably, 3-phenyl-2-propargyn-1-ol 1r with
an easily oxidized activated alcohol moiety was compatible
with our reaction conditions. Remarkably, 1,3-diethynylben-
zene was selectively oxidized, affording product 2s in 42%
yield. Finally, a complex estrone derivative was also reactive to
furnish the desired product 2t, albeit in a lower yield.
Encouraged by these results, we then evaluated the
electrochemical oxydibromination of alkynes. Gratefully,
phenylacetylene 1a reacted successfully with CH2Br2 under
our reaction conditions, forming the desired product 3a in 74%
yield (Scheme 3). Generally, alkynes with electron-rich arenes
(3b−3e) exhibited higher reactivity than electron-deficient
substrates (3f−3m). It is worth mentioning that halogens (F,
Cl, Br), ester, nitro, cyano, and even aldehyde, survived under
our reaction conditions, providing the possibility for further
structural elaboration.
Next, we turned our attention to the examination of different
halogen sources with 1a as the substrate under electrochemical
conditions (Scheme 4). For the chlorinating reagents, both
chloroform (CHCl3) and 1,2-dichloroethane (ClCH2CH2Cl)
provided 2a in high yields. Dichloromethane (CH2Cl2) and
tetrachloromethane (CCl4) were also suitable chlorinating
reagents for this transformation, leading to 2a in good yields.
On the contrary, only dibromomethane (CH2Br2) reacted very
B
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Letter
a b
,
Scheme 3. Electrochemical Oxydibromination of Alkynes
Scheme 5. Scale-Up Reaction and Radical Trapping
reaction does not require a stoichiometric amount of TBAI
(see Scheme S2 in the Supporting Information). Additionally,
cyclic voltammetry (CV) experiments (Figure 1) were carried
a
Standard conditions: constant current = 10 mA, 1a (0.3 mmol),
TBAI (0.8 equiv), LiClO4 (1.0 equiv), H2O (2.0 equiv), MeCN/
CH2Br2 (10.0 mL, 9.2/0.8) in an undivided cell with two platinum
b
electrodes, rt, 6 h. Isolated yield.
a b
,
Scheme 4. Electrochemical Oxydibromination of Alkynes
Figure 1. CV experiments.
out. A reduction peak of CHCl3 was observed at −0.94 V (vs
Ag/AgCl), as the electrochemical reduction of DCE18 and
CCl4 has been reported. Notably, with TBAI and CHCl3, a
a
16c
Standard conditions: constant current = 10 mA, 1a (0.3 mmol),
TBAI (0.8 equiv), LiClO4 (1.0 equiv), H2O (2.0 equiv), MeCN/[X]
(10.0 mL, 9.2/0.8) in an undivided cell with two platinum electrodes,
decreased reduction potential at −0.75 V (vs Ag/AgCl) was
observed. We assume that an SN2 iodination of CHCl3 with
TBAI would form ICHCl2, which was then reduced at the
cathode to generate the iodine anion and CH2Cl2.19 Notably,
the generated dichloromethane could be detected by 1H NMR
and GC-MS (see Scheme S4 in the Supporting Information).
Finally, a possible mechanism was proposed and illustrated
in Scheme 6, based on the aforementioned results from
previous reports.10,18 Initially, the chloride ion is generated
from CHCl3 by a nucleophilic substitution with I−. The
resulting chloride ion is oxidized at the anode to give a chlorine
radical. Subsequently, addition of the chlorine radical to alkyne
1a provided vinyl radical A. The resulting radical intermediate
A can be oxidized to vinyl cation B, which was then subjected
to nucleophilic attack by water to produce enol C. Enol C
rapidly combines with the chlorine radical and is then further
oxidized, affording the final oxydichlorination product 2a, as
well as a proton. In the meanwhile, I− could be regenerated by
the cathodic reduction of ICHCl2.
b
rt, 6 h. Isolated yield.
well under the standard conditions, delivering the correspond-
ing product 3a in high yield. Other common brominating
reagents such as 1,2-dichloroethane (BrCH2CH2Br), bromo-
form (CHBr3), and tetrabromomethane (CBr4) showed
inferior reaction efficiency, giving the corresponding bromina-
tion products 3a in 30−43% yields.
To further explore the potential applicability of this
oxydihalogenation protocol, we conducted the oxydichlorina-
tion of phenylacetylene 1a on a 6 mmol scale (Scheme 5a).
The reaction proceeded smoothly, and the desired 2,2-
dichloroacetophenone 2a was isolated in 65% yield after 48 h.
Some mechanistic experiments were conducted to gain some
insight into the reaction mechanism. First of all, radical
trapping reactions with TEMPO, BHT, or 1,1-diphenyl-
ethylene indicate that radical intermediates are likely involved
in this oxydichlorination process (Scheme 5b). The relevant
chlorine radical trapping product 4 could be detected by GC-
MS. Furthermore, after the first round of oxydichlorination of
phenylacetylene 1a, the second round reaction proceeded
smoothly without extra addition of TBAI, indicating that the
In summary, we have reported an electrochemical oxidative
oxydihalogenation protocol using CHCl3, CH2Cl2,
ClCH2CH2Cl, and CH2Br2 as the halogen source at room
temperature. Various valuable α,α-dihaloketones can be
constructed from readily available alkynes using this eco-
C
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Scheme 6. Possible Mechanism
REFERENCES
■
(1) (a) Srivastava, S.; Bajpai, L. K.; Batra, S.; Bhaduri, A. P.;
Maikhuri, J. P.; Gupta, G.; Dhar, J. D. In Search of New Chemical
Entities with Spermicidal and Anti-HIV Activities. Bioorg. Med. Chem.
1999, 7, 2607. (b) Qin, L.; Tian, Y.; Yu, Z.; Shi, D.; Wang, J.; Zhang,
C.; Peng, R.; Chen, X.; Liu, C.; Chen, Y.; Huang, W.; Deng, W.
Targeting PDK1 with dichloroacetophenone to inhibit acute myeloid
leukemia (AML) cell growth. Oncotarget. 2016, 7, 1395. (c) Sradhan-
jali, S.; Tripathy, D.; Rath, S.; Mittal, R.; Reddy, M. M. Over-
expression of pyruvate dehydrogenase kinase 1 in retinoblastoma: A
potential therapeutic opportunity for targeting vitreous seeds and
hypoxic regions. PLoS One 2017, 12, No. e0177744. (d) Xu, B.; Yu,
Z.; Xiang, S.; Li, Y.; Zhang, S.-L.; He, Y. Rational design of
mitochondria-targeted pyruvate dehydrogenase kinase 1 inhibitors
with improved selectivity and antiproliferative activity. Eur. J. Med.
Chem. 2018, 155, 275.
(2) Jiang, J.; Zou, H.; Dong, Q.; Wang, R.; Lu, L.; Zhu, Y.; He, W.
Synthesis of 2-Keto(hetero)aryl Benzox(thio)azoles through Base
Promoted Cyclization of 2-Amino(thio)phenols with α,α-Dihaloke-
tones. J. Org. Chem. 2016, 81, 51.
(3) (a) Vaillancourt, F. H.; Yeh, E.; Vosburg, D. A.; Garneau-
Tsodikova, S.; Walsh, C. T. Nature’s Inventory of Halogenation
Catalysts: Oxidative Strategies Predominate. Chem. Rev. 2006, 106,
3364. (b) Butler, A.; Sandy, M. Mechanistic considerations of
halogenating enzymes. Nature 2009, 460, 848. (c) Latham, J.;
Brandenburger, E.; Shepherd, S. A.; Menon, B. R. K.; Micklefield, J.
Development of Halogenase Enzymes for Use in Synthesis. Chem.
Rev. 2018, 118, 232. (d) Landry, M. L.; Burns, N. Z. Catalytic
Enantioselective Dihalogenation in Total Synthesis. Acc. Chem. Res.
2018, 51, 1260.
friendly method. This protocol is oprationally simple and easily
scaled up.
ASSOCIATED CONTENT
* Supporting Information
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The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.orglett.0c00052.
Experimental procedures and characterization data
(PDF)
(4) Saikia, I.; Borah, A. J.; Phukan, P. Use of Bromine and Bromo-
Organic Compounds in Organic Synthesis. Chem. Rev. 2016, 116,
6837.
AUTHOR INFORMATION
Corresponding Author
■
(5) (a) Chen, Z.; Zhou, B.; Cai, H.; Zhu, W.; Zou, X. Simple and
efficient methods for selective preparation of α-mono or α, α-dichloro
ketones and β-ketoesters by using DCDMH. Green Chem. 2009, 11,
275. (b) Nobuta, T.; Hirashima, S.; Tada, N.; Miura, T.; Itoh, A.
Facile aerobic photo-oxidative syntheses of α,α-dibromoacetophe-
nones from aromatic alkynes with 48% aq HBr. Tetrahedron Lett.
2010, 51, 4576. (c) Chawla, R.; Singh, A. K.; Yadav, L. D. S. Catalyst-
and Metal-Free Rapid Functionalizations of Alkynes Using TsNBr2.
Synlett 2013, 24, 1558. (d) Cho, E.; Jayaraman, A.; Lee, J.; Ko, K. C.;
Lee, S. Substituent Effect in the Synthesis of α,α-Dibromoketones,
1,2-Dibromalkenes, and 1,2-Diketones from the Reaction of Alkynes
and Dibromoisocyanuric Acid. Adv. Synth. Catal. 2019, 361, 1846.
(e) Rather, S. A.; Kumar, A.; Ahmed, Q. N. Iodine−DMSO-promoted
divergent reactivities of arylacetylenes. Chem. Commun. 2019, 55,
4511.
Shenlin Huang − Nanjing Forestry University, Nanjing, P.
R. China; orcid.org/0000-0001-7322-6981;
Email: shuang@njfu.edu.cn
Other Authors
Xiangtai Meng − Nanjing Forestry University, Nanjing, P.
R. China
Yu Zhang − Nanjing Forestry University, Nanjing, P. R.
China; orcid.org/0000-0002-2614-5975
Jinyue Luo − Nanjing Forestry University, Nanjing, P. R.
China
(6) De Kimpe, N.; Verhe, R.; De Buyck, L.; Tukiman, S.; Schamp,
N. Reactivity of n-aryl-α,α-dichlorinated arylketimines. Tetrahedron
1979, 35, 789.
Fei Wang − Nanjing Forestry University, Nanjing, P. R.
China
Xiaoji Cao − Zhejiang University of Technology,
Hangzhou, P. R. China
(7) (a) Hellwinkel, D.; Bohnet, S. Dibenzocycloocten-, Dibenzo-
chalcocin- und Diarenochalconindione. Chem. Ber. 1987, 120, 1151.
(b) Liu, J.; Li, W.; Wang, C.; Li, Y.; Li, Z. Selective 1,2-dihalogenation
and oxy-1,1-dihalogenation of alkynes by N-halosuccinimides.
Tetrahedron Lett. 2011, 52, 4320. (c) Finck, L.; Brals, J.; Pavuluri,
B.; Gallou, F.; Handa, S. Micelle-Enabled Photoassisted Selective
Oxyhalogenation of Alkynes in Water under Mild Conditions. J. Org.
Chem. 2018, 83, 7366.
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.orglett.0c00052
Notes
The authors declare no competing financial interest.
(8) (a) Zhang, X.; Wu, Y.; Zhang, Y.; Liu, H.; Xie, Z.; Fu, S.; Liu, F.
Ultrasound-assisted tandem reaction of alkynes and trihaloisocyanuric
acids by thiourea as catalyst in water. Tetrahedron 2017, 73, 4513.
(b) D’Oyley, J. M.; Aliev, A. E.; Sheppard, T. D. Regioselective
Dihalohydration Reactions of Propargylic Alcohols: Gold-Catalyzed
and Noncatalyzed Reactions. Angew. Chem., Int. Ed. 2014, 53, 10747.
(9) (a) Wu, C.; Xin, X.; Fu, Z.-M.; Xie, L.-Y.; Liu, K.-J.; Wang, Z.; Li,
W.; Yuan, Z.-H.; He, W.-M. Water-controlled selective preparation of
α-mono or α,α′-dihalo ketones via catalytic cascade reaction of
unactivated alkynes with 1,3-dihalo-5,5-dimethylhydantoin. Green
ACKNOWLEDGMENTS
■
Financial support provided by the Natural Science Foundation
of China (21502094 and 21602200), the Natural Science
Foundation of Jiangsu Province (BK20181401), and the
Natural Science Foundation of the Jiangsu Higher Education
Institutions of China (17KJA220003) is warmly acknowledged.
We are also grateful for support by the advanced analysis and
testing center of Nanjing Forestry University.
D
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pubs.acs.org/OrgLett
Letter
Chem. 2017, 19, 1983. (b) Wu, P.; Xu, S.; Xu, H.; Hu, H.; Zhang, W.
One-pot syntheses of α,α-dibromoacetophenones from aromatic
alkenes with 1,3-dibromo-5,5-dimethylhydantoin. Tetrahedron Lett.
2017, 58, 618.
Electrochemical Cobalt-Catalyzed C−H Oxygenation at Room
Temperature. J. Am. Chem. Soc. 2017, 139, 18452. (f) Xu, F.; Qian,
X.-Y.; Li, Y.-J.; Xu, H.-C. Synthesis of 4H-1,3-Benzoxazines via Metal-
and Oxidizing Reagent-Free Aromatic C−H Oxygenation. Org. Lett.
2017, 19, 6332.
(10) (a) Ye, C.; Shreeve, J. M. Structure-Dependent Oxidative
Bromination of Unsaturated C-C Bonds Mediated by Selectfluor. J.
Org. Chem. 2004, 69, 8561−8563. (b) Pandit, P.; Gayen, K. S.;
Khamarui, S.; Chatterjee, N.; Maiti, D. K. Addition of halide to p-
bond directly from aqueous NaX solution: a general strategy for
installation of two different functional groups. Chem. Commun. 2011,
47, 6933. (c) Madabhushi, S.; Jillella, R.; Mallu, K. K. R.; Godala, K.
R.; Vangipuram, V. S. A new and efficient method for the synthesis of
a,a-dihaloketones by oxyhalogenation of alkynes using oxone−KX (X
= Cl, Br, or I). Tetrahedron Lett. 2013, 54, 3993. (d) Li, Y.; Mou, T.;
Lu, L.; Jiang, X. Visible-light-promoted oxidative halogenation of
alkynes. Chem. Commun. 2019, 55, 14299.
(14) (a) Lian, F.; Sun, C.; Xu, K.; Zeng, C. Electrochemical
Dehydrogenative Imidation of N-Methyl-Substituted Benzylamines
with Phthalimides for the Direct Synthesis of Phthalimide-Protected
gem-Diamines. Org. Lett. 2019, 21, 156. (b) Liu, K.; Tang, S.; Wu, T.;
Wang, S.; Zou, M.; Cong, H.; Lei, A. Electrooxidative para-selective
C−H/N−H crosscoupling with hydrogen evolution to synthesize
triarylamine derivatives. Nat. Commun. 2019, 10, 639. (c) Yang, D.-
T.; Zhu, M.; Schiffer, Z. J.; Williams, K.; Song, X.; Liu, X.; Manthiram,
K. Direct Electrochemical Carboxylation of Benzylic C−N Bonds with
Carbon Dioxide. ACS Catal. 2019, 9, 4699. (d) Yu, Y.; Yuan, Y.; Liu,
H.; He, M.; Yang, M.; Liu, P.; Yu, B.; Dong, X.; Lei, A.
Electrochemical oxidative C−H/N−H cross-coupling for C−N
bond formation with hydrogen evolution. Chem. Commun. 2019,
55, 1809. (e) Hu, X.; Zhang, G.; Bu, F.; Nie, L.; Lei, A.
Electrochemical-Oxidation-Induced Site-Selective Intramolecular C-
(sp3)−H Amination. ACS Catal. 2018, 8, 9370. (f) Tang, S.; Wang,
S.; Liu, Y.; Cong, H.; Lei, A. Electrochemical Oxidative C-H
Amination of Phenols: Access to Triarylamine Derivatives. Angew.
Chem., Int. Ed. 2018, 57, 4737. (g) Li, C.; Kawamata, Y.; Nakamura,
H.; Vantourout, J. C.; Liu, Z.; Hou, Q.; Bao, D.; Starr, J. T.; Chen, J.;
Yan, M.; Baran, P. S. Electrochemically Enabled, Nickel-Catalyzed
Amination. Angew. Chem., Int. Ed. 2017, 56, 13088. (h) Qian, P.; Yan,
Z.; Zhou, Z.; Hu, K.; Wang, J.; Li, Z.; Zha, Z.; Wang, Z.
Electrocatalytic Intermolecular C(sp3)−H/N−H Coupling of Methyl
N-Heteroaromatics with Amines and Amino Acids: Access to
Imidazo-Fused N-Heterocycles. Org. Lett. 2018, 20, 6359. (i) Hu,
K.; Qian, P.; Su, J. H.; Li, Z.; Wang, J.; Zha, Z.; Wang, Z.
Multifunctionalization of Unactivated Cyclic Ketones via an Electro-
chemical Process: Access to Cyclic α-Enaminones. J. Org. Chem. 2019,
84, 1647. (j) Liu, S.; Li, J.; Wang, D.; Liu, F.; Liu, X.; Gao, Y.; Jie, D.;
Cheng, X. An Electrochemical Cinnamyl C-H Amination Reaction
Using Carbonyl Sulfamate. Chin. J. Chem. 2019, 37, 570. (k) Li, J.;
Huang, W.; Chen, J.; He, L.; Cheng, X.; Li, G. Electrochemical
Aziridination via Alkene Activation with a Sulfamate as Nitrogen
Source. Angew. Chem., Int. Ed. 2018, 57, 5695.
(15) (a) He, T.-J.; Ye, Z.; Ke, Z.; Huang, J. M. Stereoselective
synthesis of sulfur-containing β-enaminonitrile derivatives through
electrochemical Csp3−H bond oxidative functionalization of acetoni-
trile. Nat. Commun. 2019, 10, 833. (b) Wang, Y.; Deng, L.; Wang, X.;
Wu, Z.; Wang, Y.; Pan, Y. Electrochemically Promoted Nickel-
Catalyzed Carbon−Sulfur Bond Formation. ACS Catal. 2019, 9, 1630.
(c) Wang, P.; Tang, S.; Huang, P.; Lei, A. Electrocatalytic Oxidant-
Free Dehydrogenative C-H/S-H Cross-Coupling. Angew. Chem., Int.
Ed. 2017, 56, 3009.
(16) (a) Chen, C.; Kang, J.-C.; Mao, C.; Dong, J.-W.; Xie, Y.-Y.;
Ding, T.-M.; Tu, Y.-Q.; Chen, Z.-M.; Zhang, S.-Y. Electrochemical
halogenation/semi-pinacol rearrangement of allylic alcohols using
inorganic halide salt: an eco-friendly route to the synthesis of β-
halocarbonyls. Green Chem. 2019, 21, 4014. (b) Sun, X.; Ma, H.-X.;
Mei, T.-S.; Fang, P.; Hu, Y. Electrochemical Radical Formylox-
ylation−Bromination, − Chlorination, and − Trifluoromethylation of
Alkenes. Org. Lett. 2019, 21, 3167. (c) Zhou, Z.; Yuan, Y.; Cao, Y.;
Qiao, J.; Yao, A.; Zhao, J.; Zuo, W.; Chen, W.; Lei, A. Synergy of
Anodic Oxidation and Cathodic Reduction Leads to Electrochemical
C-H Halogenation. Chin. J. Chem. 2019, 37, 611. (d) Yuan, Y.; Yao,
A.; Zheng, Y.; Gao, M.; Zhou, Z.; Qiao, J.; Hu, J.; Ye, B.; Zhao, J.;
Wen, H.; Lei, A. Electrochemical Oxidative Clean Halogenation
Using HX/NaX with Hydrogen Evolution. iScience 2019, 12, 293.
(17) (a) Xie, L.-Y.; Duan, Y.; Lu, L.-H.; Li, Y.-J.; Peng, S.; Wu, C.;
Liu, K.-J.; Wang, Z.; He, W.-M. Fast, Base-Free and Aqueous
Synthesis of Quinolin-2(1H)-ones under Ambient Conditions. ACS
Sustainable Chem. Eng. 2017, 5, 10407. (b) Bao, W.-H; He, M.; Wang,
J.-T.; Peng, X.; Sung, M.; Tang, Z.; Jiang, S.; Cao, Z.; He, W.-M.
(11) (a) Jiang, Y.; Xu, K.; Zeng, C. Use of Electrochemistry in the
Synthesis of Heterocyclic Structures. Chem. Rev. 2018, 118, 4485.
̈
̈
(b) Karkas, M. D. Electrochemical strategies for C−H functionaliza-
tion and C−N bond formation. Chem. Soc. Rev. 2018, 47, 5786.
(c) Sauermann, N.; Meyer, T. H.; Qiu, Y.; Ackermann, L.
Electrocatalytic C−H Activation. ACS Catal. 2018, 8, 7086.
(d) Waldvogel, S. R.; Lips, S.; Selt, M.; Riehl, B.; Kampf, C. J.
Electrochemical Arylation Reaction. Chem. Rev. 2018, 118, 6706.
(e) Wiebe, A.; Gieshoff, T.; Mohle, S.; Rodrigo, E.; Zirbes, M.;
Waldvogel, S. R. Angew. Chem., Int. Ed. 2018, 57, 5594. (f) Tang, S.;
Liu, Y.; Lei, A. Electrochemical Oxidative Cross-coupling with
Hydrogen Evolution: A Green and Sustainable Way for Bond
Formation. Chem. 2018, 4, 27. (g) Yan, M.; Kawamata, Y.; Baran, P.
S. Synthetic Organic Electrochemical Methods Since 2000: On the
Verge of a Renaissance. Chem. Rev. 2017, 117, 13230. (h) Francke, R.;
Little, R. D. Redox catalysis in organic electrosynthesis: basic
principles and recent developments. Chem. Soc. Rev. 2014, 43, 2492.
(12) (a) Qiu, Y.; Scheremetjew, A.; Ackermann, L. Electro-Oxidative
C−C Alkenylation by Rhodium(III) Catalysis. J. Am. Chem. Soc.
2019, 141, 2731. (b) Li, H.; Breen, C. P.; Seo, H.; Jamison, T. F.;
Fang, Y. Q.; Bio, M. M. Ni-Catalyzed Electrochemical Decarbox-
ylative C−C Couplings in Batch and Continuous Flow. Org. Lett.
2018, 20, 1338. (c) Wu, Z. J.; Xu, H.-C. Synthesis of C3-Fluorinated
Oxindoles through Reagent-Free CrossDehydrogenative Coupling.
Angew. Chem., Int. Ed. 2017, 56, 4734. (d) Lennox, A. J. J.; Goes, S. L.;
Webster, M. P.; Koolman, H. F.; Djuric, S. W.; Stahl, S. S.
Electrochemical Aminoxyl-Mediated α-Cyanation of Secondary
Piperidines for Pharmaceutical Building Block Diversification. J. Am.
Chem. Soc. 2018, 140, 11227. (e) Hao, W.; Harenberg, J. H.; Wu, X.;
MacMillan, S. N.; Lin, S. Diastereo- and Enantioselective Formal [3 +
2] Cycloaddition of Cyclopropyl Ketones and Alkenes via Ti-
Catalyzed Radical Redox Relay. J. Am. Chem. Soc. 2018, 140, 3514.
(f) Hao, W.; Wu, X.; Sun, J. Z.; Siu, J. C.; MacMillan, S. N.; Lin, S.
Radical Redox-Relay Catalysis: Formal [3 + 2] Cycloaddition of N-
Acylaziridines and Alkenes. J. Am. Chem. Soc. 2017, 139, 12141.
(g) Lin, D.-Z.; Huang, J.-M. Electrochemical N-Formylation of
Amines via Decarboxylation of Glyoxylic Acid. Org. Lett. 2018, 20,
2112. (h) Matsumoto, K.; Fujie, S.; Ueoka, K.; Suga, S.; Yoshida, J.
An Electroinitiated Cation Chain Reaction: Intramolecular Carbon−
Carbon Bond Formation between Thioacetal and Olefin Groups.
Angew. Chem., Int. Ed. 2008, 47, 2506.
(13) (a) Bityukov, O. V.; Matveeva, O. K.; Vil’, V. A.; Kokorekin, V.
A.; Nikishin, G. I.; Terent’ev, A. O. Electrochemically Induced
Intermolecular Cross-Dehydrogenative CO Coupling of β-Diketones
and β-Ketoesters with Carboxylic Acids. J. Org. Chem. 2019, 84, 1448.
(b) Tao, X.-Z.; Dai, J.-J.; Zhou, J.; Xu, J.; Xu, H.-J. Electrochemical C-
O Bond Formation: Facile Access to Aromatic Lactones. Chem. - Eur.
J. 2018, 24, 6932. (c) Zhang, S.; Li, L.; Wang, H.; Li, Q.; Liu, W.; Xu,
K.; Zeng, C. Scalable Electrochemical Dehydrogenative Lactonization
of C(sp2/sp3)−H Bonds. Org. Lett. 2018, 20, 252. (d) Li, Y.-Q.; Yang,
Q.-L.; Fang, P.; Mei, T.-S.; Zhang, D. Palladium-Catalyzed C(sp2)−H
Acetoxylation via Electrochemical Oxidation. Org. Lett. 2017, 19,
2905. (e) Sauermann, N.; Meyer, T. H.; Tian, C.; Ackermann, L.
E
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Organic Letters
pubs.acs.org/OrgLett
Letter
Iodine-Catalyzed Odorless Synthesis of S-Thiocarbamates with
Sulfonyl Chlorides as a Sulfur Source. J. Org. Chem. 2019, 84, 6065.
(18) Liang, Y.; Lin, F.; Adeli, Y.; Jin, R.; Jiao, N. Efficient
Electrocatalysis for the Preparation of (Hetero)aryl Chlorides and
Vinyl Chloride with 1,2-Dichloroethane. Angew. Chem., Int. Ed. 2019,
58, 4566.
(19) Martin, E. T.; McGuire, C. M.; Mubarak, M. S.; Peters, D. G.
Electroreductive Remediation of Halogenated Environmental Pollu-
tants. Chem. Rev. 2016, 116, 15198.
F
https://dx.doi.org/10.1021/acs.orglett.0c00052
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