Electrochemical Radical-Radical Cross-Coupling Approach between Sodium Sulfinates and 2 H-Indazoles to 3-Sulfonylated 2 H-Indazoles

Article abstract of DOI:10.1021/acs.orglett.0c02144

A direct cross-coupling between sodium sulfinates and 2H-indazoles has been developed under electrochemical conditions. The utilization of a graphite anode and platinum cathode in an undivided cell with a constant current of 7 mA allowed the concurrent oxidations of sulfinates and 2H-indazoles to sulfonyl radical and radical cationic 2H-indazoles, facilitating the direct radical-radical coupling strategy to 3-sulfonylated 2H-indazole derivatives. The transition-metal- A nd redox-reagent-free synthetic approach should serve as a valuable synthetic tool to achieve heteroaromatic compounds.

Full text of DOI:10.1021/acs.orglett.0c02144

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Letter
Electrochemical Radical−Radical Cross-Coupling Approach between
Sodium Sulfinates and 2H‑Indazoles to 3‑Sulfonylated 2H‑Indazoles
Wansoo Kim, Hun Young Kim, and Kyungsoo Oh*
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ABSTRACT: A direct cross-coupling between sodium sulfinates
and 2H-indazoles has been developed under electrochemical
conditions. The utilization of a graphite anode and platinum
cathode in an undivided cell with a constant current of 7 mA
allowed the concurrent oxidations of sulfinates and 2H-indazoles to
sulfonyl radical and radical cationic 2H-indazoles, facilitating the
direct radical−radical coupling strategy to 3-sulfonylated 2H-
indazole derivatives. The transition-metal- and redox-reagent-free
synthetic approach should serve as a valuable synthetic tool to
achieve heteroaromatic compounds.
Scheme 1. Sulfonyl Radical Generation and Addition to
Unsaturated π Bonds
iven the wide biological activity of arylsulfonyl
derivatives across a variety of disease states, the
G
development of greener and efficient synthetic methods to
heteroaromatic sulfonyl derivatives has been a long-term goal
in organic synthesis.1 While the oxidation of aryl sulfides and
aryl sufoxides readily provides the desired sulfone moiety, the
utilization of a separate oxidation step adds an extra tool in
chemical process development. All things being equal, the
chemical process for arylsulfonyl compounds is preferred to be
convergent and to utilize a minimal amount of redox reagents
and costly transition-metal catalysts. From this angle, sodium
sulfinates fulfill the role of a dexterous sulfonyl source for
alkenes,2 alkynes,3 and arenes4 under photoredox catalysis
(Scheme 1a). While the sulfonyl radical, generated under the
photolytic conditions from sodium sulfinates, could be added
to the unsaturated π bonds, the requirement of reductants for
the photoredox processes deviates from the ideal chemical
process development. In addition, the identification of a
suitable photocatalyst to generate the sulfonyl radicals from
sodium sulfates without quenching the excited state of
photocatalyst by aromatic substrates5 presents the difficulty
associated with the inherent redox potentials of involved
substrates.
Electrochemical synthesis allows the direct anodic oxidation
of substrates without using redox reagents,6 and the simple
measurement of cyclic voltammetry of substrates provides the
total amount of voltage required for the electrochemical
oxidation processes (Scheme 1b). While sulfonyl hydrazides
have been added to a few radical acceptors under the
electrochemical conditions,7 we envisioned the use of a
greener sulfonyl radical source, sodium sulfinates for the
synthesis of hetroaromatic sulfonyl derivatives. A noteworthy
aspect of the current electrosynthetic approach is that, instead
of utilizing radical acceptor coupling partners such as alkenes,8
Received: June 29, 2020
https://dx.doi.org/10.1021/acs.orglett.0c02144
© XXXX American Chemical Society
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Letter
alkynes,9 and indole,10 the heteroaromatic compound, 2H-
indazole,11 is envisaged as a radical cationic species. The
previous contributions by the Li group12 and the Waldvogel
group13 utilized the electrochemical ortho- or para-C−H
sulfonylation of anilines and phenols via the generation of
radical cationic species from aniline and phenol derivatives.
However, the utility of such radical−radical cross-coupling
approaches to heteroaromtic compounds has not been
investigated.14 Thus, the prime goal of current electrosynthesis
of 3-sulfonylated 2H-indazoles is not to use any chemical
reagents other than electrolyte, LiClO4, for the cross-coupling
between electrochemically generated sulfonyl radicals and
radical cationic heteroaromatic species.
Table 1. Optimization of Electrochemical Cross-Coupling
between Sodium Sulfinate and 2H-Indazole
a
b
yield
entry (+)/(−) (mA) electrolyte (M)
solvent
(%)
1
2
3
4
5
6
C(+)-Pt(−) (4) LiClO4 (0.40)
CH3CN/H2O
(2.5:1)
CH3CN/H2O
(2.5:1)
CH3CN/H2O
(2.5:1)
CH3CN/H2O
(2.5:1)
CH3CN/H2O
(2.5:1)
MeOH/H2O
(2.5:1)
59
To investigate the feasibility of electrochemical cross-
coupling of sodium sulfinates and heteroaromatic compounds,
the use of sodium p-toluenesulfinate 1a and 2-phenyl-2H-
indazole 2a was chosen since our previous studies suggested
that the oxidation potentials of sodium sulfinates15 are similar
to those of 2H-indazoles.16 Indeed, the cyclic voltammetry
measurements of sodium p-toluenesulfinate 1a and 2-phenyl-
2H-indazole 2a indicated their oxidation potentials in 1.0−1.7
V (vide infra). Encouraged by the close oxidation potentials of
sodium sulfinates and 2H-indazoles, a standard electrochemical
reaction setup was applied to a 3:1 mixture of 1a and 2a in an
undivided cell with constant current conditions (Table 1).
Thus, the use of carbon rod anode and platinum plate cathode
with the 4 mA current provided the desired 3-sulfonylated 2H-
indazole 3a in 59% yield (entry 1). When the current was
changed to 7 and 10 mA (entries 2 and 3), the improved yield
of 3a was apparent in the 7 mA current to 72% (entry 2). Since
no reaction was observed in the absence of electrolyte, the
amount of electrolyte, LiClO4, was varied (entries 4 and 5). It
turned out that the use of 0.4 M LiClO4 was optimal. The
solvent screening revealed the inferior results in the MeOH/
H2O, DMA/H2O, and DMF/H2O mixtures (entries 6−8). In
addition, the amount of water in the CH3CN/H2O mixture
significantly influenced the yields of 3a (entries 9 and 10),
where the 1.3:1 ratio of CH3CN/H2O mixture provided the
product 3a in 20% (entry 10). The use of other electrolytes
such as n-Bu4ClO4 and n-Bu4BF4 lowered the yields of 3a to
37−44% (entries 11 and 12). When a carbon rod was used as
both anode and cathode (entry 13) or a platinum plate as both
anode and cathode (entry 14), the isolated yields of 3a
diminished to 14−26%. However, when the platinum plate
cathode was replaced with a nickel plate rod (entry 15), a
comparable yield of 3a was observed at 63%. Our control
experiments confirmed that the optimal use of sodium sulfinate
1a was more than 3 equiv (entries 16 and 17) and the reaction
did not take place under no current conditions (entry 18).
The optimized electrochemical cross-coupling reaction
condition was applied to the various 2H-indazoles (Scheme
2). The electronic influence of the N-phenyl group of 2H-
indazoles was minimal, providing the corresponding products
3a−3c in 69−74% yields. However, the presence of a tert-butyl
group and halogen atoms lowered the yields of products 3d−
C(+)-Pt(−) (7) LiClO4 (0.40)
72
56
55
52
0
C(+)-Pt(−)
LiClO4 (0.40)
(10)
C(+)-Pt(−) (7) LiClO4 (0.27)
C(+)-Pt(−) (7) LiClO4 (0.53)
C(+)-Pt(−) (7) LiClO4 (0.40)
7
8
9
C(+)-Pt(−) (7) LiClO4 (0.40)
C(+)-Pt(−) (7) LiClO4 (0.40)
C(+)-Pt(−) (7) LiClO4 (0.40)
DMA/H2O (2.5:1)
DMF/H2O (2.5:1)
CH3CN/H2O
(3:0.5)
18
32
71
10
11
12
13
14
15
16
17
18
C(+)-Pt(−) (7) LiClO4 (0.40)
CH3CN/H2O
(2:1.5)
CH3CN/H2O
(2.5:1)
20
37
44
26
14
63
63
73
0
C(+)-Pt(−) (7) n-Bu4ClO4
(0.40)
C(+)-Pt(−) (7) n-Bu4BF4 (0.40) CH3CN/H2O
(2.5:1)
CH3CN/H2O
(2.5:1)
CH3CN/H2O
(2.5:1)
CH3CN/H2O
(2.5:1)
CH3CN/H2O
(2.5:1)
CH3CN/H2O
(2.5:1)
CH3CN/H2O
(2.5:1)
C(+)-C(−) (7) LiClO4 (0.40)
Pt(+)-Pt(−)
LiClO4 (0.40)
LiClO4 (0.40)
(7)
C(+)-Ni(−)
(7)
c
C(+)-Pt(−) (7) LiClO4 (0.40)
C(+)-Pt(−) (7) LiClO4 (0.40)
C(+)-Pt(−) (0) LiClO4 (0.40)
d
a
Reaction using 1a (0.33 mmol), 2a (0.10 mmol), and electrolyte in
solvent (M) in an undivided cell with constant current of 7 mA under
b
c
argon for 2 h. Isolated yield of 3a. Reaction using 2 equiv of 1a.
d
Reaction using 4 equiv of 1a.
was further investigated using 5-fluoro-2H-indazoles 3m−3o,
5-chloro-2H-indazoles 3p and 3q, 6-methyl-2H-indazole 3r,
and 5,6-dioxolanyl-2H-indazole derivative 3s.
The substrate scope of sodium sulfinates in the current
cross-coupling reaction is illustrated in Scheme 3. The para-
substituted benzenesulfinates readily participated in the
reaction to give the desired products 3t−3z in 35−71% yields.
Among them, the 4-tert-butyl-substituted product 3v and the
4-cyano-substituted product 3z were obtained in 35−40%
yields. However, the current electrochemical cross-coupling
reaction did not tolerate the nitro group 3za due to the
preferential reduction capability of the nitro group. The
presence of chlorine atom somewhat lowered the yields of
products 3zb and 3zc to 32−48% yields. The substrate
limitation of the current electrochemical cross-coupling
reaction was apparent upon using 3-cyano-phenyl and
naphthyl-substituted sulfinates, where the reaction stopped
3i, possibly due to the side reaction via electrochemical Csp2
−
C(CH3)3 and Csp2−halogen bond cleavages. Indeed, the CF3
group-containing 2H-indzole 3g was obtained in 32% yield,
but the nitro-containing indazole 3h could not be prepared
under the electrochemical conditions. Nevertheless, the
current electrochemical cross-coupling reaction tolerated
methoxy 3k and dimethyl group 3l, providing the synthetically
useful level of products. The electronic effect of 2H-indazoles
B
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sulfonylated-2H-indazoles 3zi−3zk were obtained in 20−68%
yields.
Scheme 2. Substrate Scope of Cross-Coupling between
Sodium Sulfinate 1a and 2H-Indazoles
The mechanistic insight of the current electrochemical cross-
coupling reactions has been obtained from the cyclic
voltammograms (CV) of sodium p-toluenesulfinate 1a and 2-
phenyl-2H-indazole 2a (Scheme 4). Thus, the sodium p-
Scheme 4. Cyclic Voltammograms and Control Experiments
toluenesulfinate 1a was oxidized around 1.0 V (green curve),
and the 2-phenyl-2H-indazole 2a was oxidized at 1.7 V (red
curve). The CV measurement of the reaction mixture indicated
the two oxidation waves (blue curve), each corresponding to
the respective reactant, 1a and 2a. The close oxidation
potentials between sulfinates 1 and 2H-indazoles 2 appear to
be critical in the radical−radical cross-coupling strategy since
sodium naphthalene-2-sulfinates 1j with lower oxidation
potential of 0.7 V, opposed to 1a with 1.0 V, provided the
product 3ze in a low yield of 15%.17 Our control experiments
confirmed no reaction in the absence of current or in the
presence of a radical inhibitor, TEMPO. Also, the use of
sodium sulfinates was not essential in this reaction since
sulfinic acid 4a equally worked to give the desired product 3a
in 72% yield. Nevertheless, the use of sodium sulfinates is more
practical due to the enhanced stability over sulfinic acids in
general.18
a
Reaction in 1 mmol scale for 24 h.
Scheme 3. Further Substrate Scope for Sodium Sulfinates
and 2H-Indazoles
Scheme 5 illustrates the mechanistic proposal based on the
CV measurements and control experimental data. Thus, it is
reasonable to speculate the anodic oxidation of sulfinate 1 to
the sulfonyl radical A under the electrochemical oxidation
conditions. The soon-to-be followed oxidation of 2H-indazole
2 to the 2H-indazole radical cation B occurs at around 1.7 V.
The radical−radical cross-coupling between A and B leads to
the formation of cationic species C that in turn gives up a
proton to give the product 3. The cathodic reduction of
protons to hydrogen gas completes the overall electrochemical
cross-coupling of sulfinates and 2H-indazoles.
after <20% conversion to give 3zd and 3ze in 15−18% yields.
The thiophenyl-substituted sulfinate was tolerated in the
reaction to give the desired product 3zf in 65% yield, and
the electronically different sulfinates and 2H-indazoles
provided 3zg and 3zh in 47−70% yields. The utilization of
alkyl sulfinates was also possible, where the desired 3-
In summary, we have developed the electrochemical
radical−radical cross-coupling strategy for the synthesis of 3-
sulfonylated 2H-indazoles. The current transition-metal-free
C
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Notes
Scheme 5. Mechanistic Rationale for Radical−Radical
Cross-Coupling Pathway
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This research was supported by the National Research
Foundation of Korea (NRF) grant funded by the Korean
government (MSICT) (NRF-2015R1A5A1008958 and NRF-
2019R1A2C2089953).
REFERENCES
■
(1) For recent reviews, see: (a) Emmett, E. J.; Willis, M. C. The
Development and Application of Sulfur Dioxide Surrogates in
Synthetic Organic Chemistry. Asian J. Org. Chem. 2015, 4, 602−
611. (b) Liu, N.-W.; Liang, S.; Manolikakes, G. Recent Advances in
the Synthesis of Sulfones. Synthesis 2016, 48, 1939−1973.
(c) Shaaban, S.; Liang, S.; Liu, N.-W.; Manolikakes, G. Synthesis of
Sulfones via Selective C-H Functionalization. Org. Biomol. Chem.
2017, 15, 1947−1955. (d) Zhu, J.; Yang, W.-C.; Wang, X.-d.; Wu, L.
Photoredox Catalysis in C-S Bond Construction: Recent Progress in
Photo-Catalyzed Formation of Sulfones and Sulfoxides. Adv. Synth.
Catal. 2018, 360, 386−400. (e) Liu, J.; Zheng, L. Recent Advances in
Transition-Metal-Mediated Chelation-Assisted Sulfonylation of Un-
activated C-H Bonds. Adv. Synth. Catal. 2019, 361, 1710−1732.
(f) Trost, B. M.; Kalnmals, C. A. Sulfones as Chemical Chameleons:
Versatile Synthetic Equivalent of Small-Molecule Synthons. Chem. -
Eur. J. 2019, 25, 11193−11213.
(2) (a) Meyer, A. U.; Jager, S.; Hari, D. P.; Konig, B. Visible Light-
Mediated Metal-Free Synthesis of Vinyl Sulfones from Aryl Sulfinates.
Adv. Synth. Catal. 2015, 357, 2050−2054. (b) Pagire, S.; Paria, S.;
Reiser, O. Synthesis of β-Hydroxysulfones from Sulfonyl Chlorides
and Alkenes Utilizing Visible Light Photocatalytic Sequences. Org.
Lett. 2016, 18, 2106−2109. (c) Wang, L.-J.; Chen, M.; Qi, L.; Xu, Z.;
Li, W. Copper-Mediated Oxysulfonylation of Alkenyl Oximes with
Sodium Sulfinates: A Facile Synthesis of Isoxazoline Featuring a
Sulfone Substituent. Chem. Commun. 2017, 53, 2056−2059. For a
recent review, see: (d) Guo, W.; Tao, W.; Tan, W.; Zhao, M.; Zheng,
L.; Fan, X. Recent Advances in Photocatalytic C-S/P-S Bond
Formation via the Generation of Sulfur Centered Radicals and
Functionalization. Org. Chem. Front. 2019, 6, 2048−2066.
(3) (a) Wang, H.; Lu, Q.; Chiang, C.-W.; Luo, Y.; Zhou, J.; Wang,
G.; Lei, A. Markovnikov-Selective Radical Addition of S-Nucleophiles
to Terminal Alkynes through a Photoredox Process. Angew. Chem.,
Int. Ed. 2017, 56, 595−599. (b) Chakrasali, P.; Kim, K.; Jung, Y.-S.;
Kim, H.; Han, S. B. Visible-Light-Mediated Photoredox-Catalyzed
Regio- and Stereoselective Chlorosulfonylation of Alkynes. Org. Lett.
2018, 20, 7509−7513.
(4) (a) Yue, H.; Zhu, C.; Rueping, M. Cross-Coupling of Sodium
Sulfinates with Aryl, Heteroaryl, and Vinyl Halides by Nickel/
Photoredox Dual Catalysis. Angew. Chem., Int. Ed. 2018, 57, 1371−
1375. (b) Johnson, T. C.; Elbert, B. L.; Farley, A. J. M.; Gorman, T.
W.; Genicot, C.; Lallemand, B.; Pasau, P.; Flasz, J.; Castro, J. L.;
MacCoss, M.; Dixon, D. J.; Paton, R. S.; Schofield, C. J.; Smith, M. D.;
Willis, M. C. Direct Sulfonylation of Anilines Mediated by Visible
Light. Chem. Sci. 2018, 9, 629−633. (c) Cabrera-Afonso, M. J.; Lu, Z.-
P.; Kelly, C. B.; Lang, S. B.; Dykstra, R.; Gutierrez, O.; Molander, G.
A. Engaging Sulfinate Salts via Ni/Photoredox Dual Catalysis Enables
Facile Csp2-SO2R Coupling. Chem. Sci. 2018, 9, 3186−3191.
(5) Bock, C. R.; Connor, J. A.; Gutierrez, A. R.; Meyer, T. J.;
Whitten, D. G.; Sullivan, B. P.; Nagle, J. K. Estimation of Excited-State
Redox Potentials by Electron-Transfer Quenching. Application of
Electron-Transfer Theory to Excited-State Redox Processes. J. Am.
Chem. Soc. 1979, 101, 4815−4824.
and redox-reagent-free synthetic approach to heteroaromatic
compounds requires a simple electrochemistry setup without
any added reaction components other than electrolyte. The
present electrochemical synthesis of 3-sulfonylated 2H-
indazoles has been conceived from the cyclic voltammograms
of two starting materials: sodium sulfinates and 2H-indazoles.
Given that the electrochemical experiment setups are widely
available nowadays, the electrochemical radical−radical cross-
coupling strategy should be applicable to the preparation of
other heterocyclic compounds. We are currently pursuing the
electrochemical synthesis of heterocycles of medicinal interest,
and our results will be reported in due course.
̈
̈
ASSOCIATED CONTENT
* Supporting Information
■
sı
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.orglett.0c02144.
Experimental procedures and characterization data for
all new compounds, electrasyn reaction, electrochemical
sulfonylation, mechanism study: cyclic voltammetry
(CV), NMR Spectra (PDF)
FAIR data, including the primary NMR FID files, for
compounds 1c−1e, 1g−1p, 2a−2r, 3a−3g, 3i−3z, and
3zb−3zk (ZIP)
AUTHOR INFORMATION
Corresponding Author
■
Kyungsoo Oh − Center for Metareceptome Research, Graduate
School of Pharmaceutical Sciences, Chung-Ang University, Seoul
06974, Republic of Korea; orcid.org/0000-0002-4566-
6573; Email: kyungsoooh@cau.ac.kr
Authors
Wansoo Kim − Center for Metareceptome Research, Graduate
School of Pharmaceutical Sciences, Chung-Ang University, Seoul
06974, Republic of Korea
Hun Young Kim − Center for Metareceptome Research,
Graduate School of Pharmaceutical Sciences, Chung-Ang
University, Seoul 06974, Republic of Korea; orcid.org/
0000-0002-8461-8910
(6) For reviews, see: (a) Yoshida, J.; Kataoka, K.; Horcajada, R.;
Nagaki, A. Modern Strategies in Electroorganic Synthesis. Chem. Rev.
2008, 108, 2265−2299. (b) Francke, R.; Little, R. D. Redox Catalysis
in Organic Electrosynthesis: Basic Principles and Recent Develop-
ments. Chem. Soc. Rev. 2014, 43, 2492−2521. (c) Yan, M.; Kawamata,
Y.; Baran, P. S. Synthetic Organic Electrochemical Method Since
Complete contact information is available at:
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Letter
2000: On the Verge of a Renaissance. Chem. Rev. 2017, 117, 13230−
13319. (d) Wang, H.; Gao, X.; Lv, Z.; Abdelilah, T.; Lei, A. Recent
Advances in Oxidative R1-H/R2-H Cross-Coupling with Hydrogen
Evolution via Photo-/Electrochemistry. Chem. Rev. 2019, 119, 6769−
6787.
lation of N,N-Disubstituted Anilines with Sulfinates. Chem. Commun.
2019, 55, 8995−8998.
(13) (a) Nikl, J.; Lips, S.; Schollmeyer, D.; Franke, R.; Waldvogel, S.
R. Direct Metal- and Reagent-Free Sulfonylation of Phenols with
Sodium Sulfinates by Electrosynthesis. Chem. - Eur. J. 2019, 25,
6891−6895. (b) Nikl, J.; Ravelli, D.; Schollmeyer, D.; Waldvogel, S.
R. Straightforward Electrochemical Sulfonylation of Arenes and
Aniline Derivatives Using Sodium Sulfinates. ChemElectroChem
2019, 6, 4450−4455.
(7) (a) Zhao, Y.; Lai, Y.-L.; Du, K.-S.; Lin, D.-Z.; Huang, J.-M.
Electrochemical Decarboxylative Sulfonylation of Cinnamic Acids
with Aromatic Sulfonylhydrazides to Vinyl Sulfones. J. Org. Chem.
2017, 82, 9655−9661. (b) Yuan, Y.; Cao, Y.; Lin, Y.; Li, Y.; Huang,
Z.; Lei, A. Electrochemical Oxidative Alkoxysulfonylation of Alkenes
Using Sulfonyl Hydrazines and Alcohols with Hydrogen Evolution.
ACS Catal. 2018, 8, 10871−10875. (c) Mo, Z.-Y.; Swaroop, T. R.;
Tong, W.; Zhang, Y.-Z.; Tang, H.-T.; Pan, Y.-M.; Sun, H.-B.; Chen,
Z.-F. Electrochemical Sulfonylation of Thiols with Sulfonyl
Hydrazides: A Metal- and Oxidant-Free Protocol for the Synthesis
of Thiosulfonates. Green Chem. 2018, 20, 4428−4432. (d) Mulina, O.
M.; Zhironkina, N. V.; Paveliev, S. A.; Demchuk, D. V.; Terent’ev, A.
O. Electrochemically Induced Synthesis of Sulfonylated N-Unsub-
stituted Enamines from Vinyl Azides and Sulfonyl Hydrazides. Org.
Lett. 2020, 22, 1818−1824.
(8) (a) Qian, P.; Bi, M.; Su, J.; Zha, Z.; Wang, Z. Electrosynthesis of
(E)-Vinyl Sulfones Directly from Cinnamic Acids and Sodium
Sulfinates via Decarboxylative Sulfono Functionalization. J. Org.
Chem. 2016, 81, 4876−4882. (b) Zheng, M.-W.; Yuan, X.; Cui, Y.-S.;
Qiu, J.-K.; Li, G.; Guo, K. Electrochemical Sulfonylation/Hetero-
arylation of Alkenes via Distal Heteroaryl ipso-Migration. Org. Lett.
2018, 20, 7784−7789 (using sulfinic acids). (c) Mei, H.; Liu, J.; Guo,
Y.; Han, J. Electrochemical Alkoxysulfonylation Difunctionalization of
Styrene Derivatives Using Sodium Sulfinates as Sulfonyl Sources. ACS
Omega 2019, 4, 14353−14359.
(14) During the preparation of this manuscript, the Sarkar group
reported the mechanistically different electrochemical synthetic
approach to 3-sulfonylated 2H-indazoles using sulfonyl hydrazides
(and 2H-indazoles as radical acceptors), see: Mahanty, K.; Maiti, D.;
Sarkar, S. D. Regioselective C-H Sulfonylation of 2H-Indazoles by
Electrosynthesis. J. Org. Chem. 2020, 85, 3699−3708.
(15) Bogonda, G.; Patil, D.; Kim, H. Y.; Oh, K. Visible Light-
Promoted Thiyl Radical Generation from Sodium Sulfinates: A
Radical-Radical Coupling to Thioesters. Org. Lett. 2019, 21, 3774−
3779.
(16) Bogonda, G.; Kim, H. Y.; Oh, K. Direct Acyl Radical Addition
to 2H-Indazoles Using Ag-Catalyzed Decarboxylative Cross-Coupling
of α-Keto Acids. Org. Lett. 2018, 20, 2711−2715.
(17) Our results suggested that the closer the oxidation potentials
between two reagents, sulfinates and 2H-indazoles, leads to better
electrochemical radical−radical cross-coupling efficiency; see Schemes
2 and 3.
(18) (a) Aziz, J.; Messaoudi, S.; Alami, M.; Hamze, A. Sulfinate
Derivatives: Dual and Versatile Partners in Organic Synthesis. Org.
Biomol. Chem. 2014, 12, 9743−9759. (b) Mei, H.; Romana, P.; Wang,
L.; Li, Z.; Roschenthaler, G.-V.; Han, J. Chemistry of Electrochemical
Oxidative Reactions of Sulfinates Salts. Green Chem. 2020, 22, 3028−
3059.
(9) Wen, J.; Shi, W.; Zhang, F.; Liu, D.; Tang, S.; Wang, H.; Lin, X.-
M.; Lei, A. Electrooxidative Tandem Cyclization of Activated Alkynes
with Sulfinic Acids to Access Sulfonated Indenones. Org. Lett. 2017,
19, 3131−3134.
(10) Feng, M.-L.; Xi, L.-Y.; Chen, S.-Y.; Yu, X.-Q. Electrooxidative
Metal-Free Dehydrogenative α-Sulfonylation of 1H-Indole with
Sodium Sulfinates. Eur. J. Org. Chem. 2017, 2017, 2746−2750.
(11) For a recent review, see: (a) Zhang, S.-G.; Liang, C.-G.; Zhang,
W.-H. Recent Advances in Indazole-Containing Derivatives: Synthesis
and Biological Perspectives. Molecules 2018, 23, 2783. For recent
examples, see: (b) Zhang, R.; Liu, Z.; Peng, Q.; Zhou, Y.; Xu, L.; Pan,
X. Access to 2-Substituted-2H-Indazoles via a Copper-Catalyzed
Regioselective Cross-Coupling Reaction. Org. Biomol. Chem. 2018, 16,
1816−1822. (c) Singsardar, M.; Laru, S.; Mondal, S.; Hajra, A.
Visible-Light-Induced Regioselective Cross-Dehydrogenative Cou-
pling of 2H-Indazoles with Ethers. J. Org. Chem. 2019, 84, 4543−
4550. (d) Gao, P.; Cheng, Y.-B.; Yang, F.; Guo, L.-N.; Duan, X.-H.
Iron(II)-Catalyzed Direct C-H Cyanoalkylation of 2H-Indazoles and
Coumarins via Radical C-C Bond Cleavage. Tetrahedron Lett. 2019,
60, 150967. (e) Singsardar, M.; Dey, A.; Sarkar, R.; Hajra, A. Visible-
Light-Induced Organophotoredox-Catalyzed Phosphonylation of 2H-
Indazoles with Diphosphine Oxide. J. Org. Chem. 2018, 83, 12694−
12701. (f) Murugan, A.; Babu, V. N.; Polu, A.; Sabarinathan, N.;
Bakthadoss, M.; Sharada, D. S. Regioselective C3-H Trifluoromethy-
lation of 2H-Indazole under Transition-Metal-Free Photoredox
Catalysis. J. Org. Chem. 2019, 84, 7796−7803. (g) Dey, A.; Hajra,
A. Iodine-Catalyzed Selenylation of 2H-Indazole. J. Org. Chem. 2019,
84, 14904−14910. (h) Dey, A.; Hajra, A. Potassium Persulfate-
Mediated Thiocyanation of 2H-Indazole under Iron-Catalysis. Adv.
Synth. Catal. 2019, 361, 842−849. (i) Aganda, K. C. C.; Kim, J.; Lee,
A. Visible-Light-Mediated Direct C3-Arylation of 2H-Indazoles
Enabled by an Electron-Donor-Acceptor Complex. Org. Biomol.
Chem. 2019, 17, 9698−9702. (j) Ghosh, P.; Mondal, S.; Hajra, A. tert-
Butyl Hydroperoxide-Mediated Oxo-Sulfonylation of 2H-Indazoles
with Sulfinic Acid toward Indazol-3(2H)-ones. Org. Lett. 2020, 22,
1086−1090.
(12) Wu, Y.-C.; Jiang, S.-S.; Luo, S.-Z.; Song, R.-J.; Li, J.-H.
Transition-Metal- and Oxidant-Free Directed Anodic C-H Sulfony-
E
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