Metal-Free Electrochemical Synthesis of Sulfonamides Directly from (Hetero)arenes, SO2, and Amines

Article abstract of DOI:10.1002/anie.202016164

Sulfonamides are among the most important chemical motifs in pharmaceuticals and agrochemicals. However, there is no methodology to directly introduce the sulfonamide group to a non-prefunctionalized aromatic compound. Herein, we present the first dehydrogenative electrochemical sulfonamide synthesis protocol by exploiting the inherent reactivity of (hetero)arenes in a highly convergent reaction with SO₂ and amines via amidosulfinate intermediate. The amidosulfinate serves a dual role as reactant and supporting electrolyte. Direct anodic oxidation of the aromatic compound triggers the reaction, followed by nucleophilic attack of the amidosulfinate. Boron-doped diamond (BDD) electrodes and a HFIP–MeCN solvent mixture enable selective formation of the sulfonamides. In total, 36 examples are demonstrated with yields up to 85 %.

Full text of DOI:10.1002/anie.202016164

Angewandte
Communications
Chemie
How to cite: Angew. Chem. Int. Ed. 2021, 60, 5056–5062
International Edition:
German Edition:
doi.org/10.1002/anie.202016164
doi.org/10.1002/ange.202016164
Electrochemistry
Hot Paper
Metal-Free Electrochemical Synthesis of Sulfonamides
Directly from (Hetero)arenes, SO2, and Amines
Stephan P. Blum, Tarik Karakaya, Dieter Schollmeyer, Artis Klapars, and
Siegfried R. Waldvogel*
In memory of FranÅois Diederich
Angewandte
Chemie
5056
ꢀ 2020 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH
Angew. Chem. Int. Ed. 2021, 60, 5056 –5062

Angewandte
Communications
Chemie
Abstract: Sulfonamides are among the most important
chemical motifs in pharmaceuticals and agrochemicals. How-
ever, there is no methodology to directly introduce the
sulfonamide group to a non-prefunctionalized aromatic com-
pound. Herein, we present the first dehydrogenative electro-
chemical sulfonamide synthesis protocol by exploiting the
inherent reactivity of (hetero)arenes in a highly convergent
reaction with SO2 and amines via amidosulfinate intermediate.
The amidosulfinate serves a dual role as reactant and
supporting electrolyte. Direct anodic oxidation of the aromatic
compound triggers the reaction, followed by nucleophilic
attack of the amidosulfinate. Boron-doped diamond (BDD)
electrodes and a HFIP–MeCN solvent mixture enable selective
formation of the sulfonamides. In total, 36 examples are
demonstrated with yields up to 85%.
Scheme 1. Sulfonamide-containing drugs.
S
ulfonamides exhibit unique antibacterial properties[1–3] and
are classified as “highly important antimicrobials” by WHO.[4]
Gerhard Domagk was awarded the Nobel prize in 1939 for
introducing them as antibacterial chemotherapeutic agents.[2]
Even though sulfonamides rarely occur in nature,[5–7] it was
later on discovered that they reveal numerous other biolog-
ical activities.[8,9] Anti-tumoral,[10] anti-obesity,[11] and anti-
inflammatory[8,12] activity are just a few examples.
The protease inhibitor Fosamprenavir (1) is an anti-HIV
prodrug (Scheme 1).[13,14] Hydrochlorothiazide (2) is used
against high blood pressure.[14,15] The vasodilatory drug
Sildenafil (3) became well-known for the treatment of erectile
dysfunction[14,16] and Probenecid (4) is a well-established drug
to medicate gout.[14,17] Additionally, sulfonamides are
common chemical motifs in agrochemicals,[5,18] plasticizers,[19]
dyes/pigments,[20] and polymers.[21] The high chemical and
metabolic stability[6,7,22] combined with the interesting physi-
cochemical properties[23] makes sulfonamide functionalities
highly important in bioactive molecules.[3,22] For this reason,
extensive research effort has been put into the development
of more efficient syntheses of sulfonamides.[24]
Traditionally, sulfonamides are directly prepared by
reaction of an amine with a sulfonyl chloride (Scheme 2).
However, sulfonyl chlorides are moisture-sensitive[25] and
many may not be amenable to long-term storage.[3] They can
be obtained by treatment of chlorosulfuric acid with the
Scheme 2. Selected strategies for the synthesis of sulfonamides.
DABSO=1,4-diazabicyclo[2.2.2]octane–bis(sulfur dioxide) adduct;
DIPEA=N,N-diisopropylethylamine.
[*] S. P. Blum, T. Karakaya, Dr. D. Schollmeyer, Prof. Dr. S. R. Waldvogel
Department of Chemistry, Johannes Gutenberg University Mainz
Duesbergweg 10–14, Mainz (Germany)
corresponding aromatic compound. Harsh reaction condi-
tions and multiple equivalents[26] of the corrosive chlorosul-
furic acid are often required and the selectivity is limited to
the inherent reactivity of the aromatic compound, which can
result in regioisomer mixtures.[27,28] An interesting alternative
method was reported by Willis and co-workers featuring the
CuII-catalyzed synthesis of sulfonamides starting from the
corresponding arylboronic acid with DABSO as SO2 source.[6]
However, harsh reaction conditions, the cost of DABSO,
necessary prefunctionalization of the arene and excess of the
boronic acid component are drawbacks in this approach. Just
recently, Noꢀl and co-workers published the electrochemical
conversion of thiophenols to sulfonamides in presence of an
amine.[7] Despite the convergent nature, this methodology
suffers from certain disadvantages, such as the need of
E-mail: waldvogel@uni-mainz.de
Dr. A. Klapars
Department of Process Research and Development, Merck & Co.,
Inc.
P.O. Box 2000, Rahway, New Jersey 07065 (USA)
Supporting information and the ORCID identification number(s) for
the author(s) of this article can be found under:
https://doi.org/10.1002/anie.202016164.
ꢀ 2020 The Authors. Angewandte Chemie International Edition
published by Wiley-VCH GmbH. This is an open access article under
the terms of the Creative Commons Attribution Non-Commercial
NoDerivs License, which permits use and distribution in any
medium, provided the original work is properly cited, the use is non-
commercial and no modifications or adaptations are made.
Angew. Chem. Int. Ed. 2021, 60, 5056 –5062
ꢀ 2020 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH www.angewandte.org
5057

Angewandte
Communications
Chemie
Table 1: Optimization reactions of the model substrates.
a supporting electrolyte. Furthermore, thiophenols are con-
sidered air sensitive, toxic and foul-smelling and only a limited
selection is available commercially.[29] In the past decades,
numerous other publications dealing with sulfonamide syn-
theses were reported.[3,22,27,30,31] Once again, all methods are
based on prefunctionalized scaffolds. Herein, we present the
first one-step synthesis of sulfonamides, directly from (het-
ero)arenes, SO2, and amines in a multi-component reaction
Entry
Deviation from the standard conditions[a]
Yield [%][b]
1
2
3
4
5
6
7
8
none
HFIP/MeCN (9:1)
HFIP/MeCN (1:9)
HFIP/DMSO (1:1)
HFIP/CH2Cl2 (1:1)
undivided cell
1.5 m SO2
54
39
traces
traces
57
13
53
55
72
via electrochemical C H activation.[32] An amine and SO2 are
À
1.5 m SO2, 12 mAcmÀ2
1.5 m SO2, 12 mAcmÀ2, 3.5 F
1.5 m SO2, 12 mAcmÀ2, 5.5 F
1.5 m SO2, 12 mAcmÀ2, 3.5 F, no DIPEA
1.5 m SO2, 12 mAcmÀ2, 3.5 F,
Pt electrodes
proposed to form the amidosulfinate intermediate, which
9
takes a dual role as nucleophile and supporting electrolyte.
10
11
12
40
31
59
[31,33]
The feedstock chemical SO2
is incorporated into the
substrate in an atom-economical way, avoiding the use of
expensive SO2 surrogates. Inexpensive electricity serves as
“green” oxidant—electrochemical reactions in general are
considered sustainable, inherently safe, and scalable.[34,35]
BDD electrodes[36] and the solvent 1,1,1,3,3,3-hexafluoropro-
pan-2-ol (HFIP),[37] important to the success of this trans-
formation, enable novel electrochemical reactivity.[38] More-
over, the robustness of such transformations[39] and the long
life-time of BDD electrodes[40] in combination with the
possibility of HFIP recovery[35,41] make this approach even
more environmentally friendly. Just recently, our group
reported the electrochemical synthesis of alkyl arylsulfonates
from arenes, alcohols, and SO2 in a multi-component reac-
tion,[28] and this encouraged us to explore the possibility of
a direct electrochemical synthesis of sulfonamides.
13
14
15
1.5 m SO2, 12 mAcmÀ2, 3.5 F,
graphite electrodes
49
72
0
1.5 m SO2, 12 mAcmÀ2, 3.5 F
glassy carbon electrodes
1.5 m SO2, no electricity
[a] Standard conditions: 1,2,3-trimethoxybenzene (0.6 mmol, 0.1 m),
morpholine (3 eq.), DIPEA (4 eq.), SO2 (1.2 m), HFIP/MeCN=1:1
(vol%), r.t., divided cell (glass frit), BDD electrodes, j=7 mAcmÀ2
,
Q=2.5 F. [b] Combined yield of 5a and 5b determined by internal NMR
standard (1,3,5-trimethoxybenzene); DMSO=dimethylsulfoxide.
the yield to 72% (Table 1, entry 9), though 5.5 F resulted in
less product formation due to overoxidation of the sulfona-
mide (Table 1, entry 10). Omitting of DIPEA decreased the
yield and resulted in lower conductivity of the electrolyte
(Table 1, entry 11). Graphite and platinum electrodes
(Table 1, entries 12 and 13) provided worse results, but it is
noteworthy that glassy carbon showed similar reactivity
compared to BDD electrodes (Table 1, entry 14). No product
was found when the electricity was omitted (Table 1,
entry 15). Finally, the conditions from Table 1, entry 9 were
chosen for further reactions.
After completion of the optimization process, the sub-
strate scope was expanded in regard to different arenes in
combination with morpholine (Scheme 4). Amazingly, sulfon-
amide 6 was isolated in 80% yield. Remarkably, bromo,
chloro, fluoro, and iodo substituents were tolerated in 7a/7b–
12, which provides an opportunity for further functionaliza-
tion via metal-catalyzed coupling reactions.[42] The sulfon-
amide derivatives (13a/13b) of veratrole were obtained in
79% combined yield.
Guided by our previous studies on arylsulfonates,[28] we
chose 1,2,3-trimethoxybenzene as arene model substrate for
reaction optimization in combination with morpholine as
amine. We were delighted to observe the formation of the
desired sulfonamide as two regioisomers 5a and 5b in a 6:1
ratio as depicted in Scheme 3. Reaction optimization showed
that a 1:1 solvent mixture of HFIP/MeCN was superior
(Table 1, entry 1) in comparison to excess HFIP (Table 1,
entry 2) or excess MeCN (Table 1, entry 3). HFIP/DMSO
(1:1) proved to be unsuitable for this reaction (Table 1,
entry 4), whereas HFIP/CH2Cl2 (1:1) gave 57% combined
yield (Table 1, entry 5). Electrolysis in undivided cells
resulted in lower product formation (Table 1, entry 6).
Slight increase of the SO2 concentration to 1.5 m (Table 1,
entry 7) had no significant influence on the reaction. Like-
wise, the increase to 12 mAcmÀ2 current density also did not
show any remarkable difference (Table 1, entry 8). The
modulation of the applied amount of charge to 3.5 F increased
Two further regioisomers with roughly the same ratio
were formed with 2-methyl-1,4-dimethoxybenzene as starting
material, giving 14a/14b in 61% combined yield and anisole
derivatives 15a/15b were obtained in 31% yield. The
sulfonamides 16 (37%) and 17 (34%) were in similar yield
range, whereas benzodioxane derivatives 18a/18b gave 79%.
Thiophene-derived heterocyclic structure 19 only provided
11% yield and benzodioxole derivative 20 gave 42%. Further
halogen-containing benzodioxoles provided lower yields (21,
26%; 22, 25%). Finally, two natural products (methyleugenol
and safrol) containing potentially sensitive alkene function-
ality were successfully converted to their sulfonamide deriv-
ative (23, 23%; 24, 16%). In general, less electron-rich arenes
were ineligible for this reaction.
Scheme 3. General reaction scheme for the electrochemical synthesis
of sulfonamides during the optimization process. [a] The 6:1 regioiso-
meric ratio was determined according to the crude NMR of entry 9
(Table 1).
5058
www.angewandte.org ꢀ 2020 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH
Angew. Chem. Int. Ed. 2021, 60, 5056 –5062

Angewandte
Communications
Chemie
Scheme 5. Sulfonamide substrate scope of different amines. [a] Reac-
tion conditions: 1,4-dimethoxybenzene (0.6 mmol, 0.1 m), amine sub-
strate (3 equiv.), DIPEA (4 equiv.), SO2 (1.5 m), HFIP/MeCN=1:1,
divided cell (glass frit), r.t., BDD electrodes, j=12 mAcmÀ2, Q=3.5 F;
[b] l-proline methyl ester hydrochloride (3 equiv.) and DIPEA (5 equiv.)
were used.
Next, the scalability of the reaction was investigated. A
simple H-type glass cell, divided by a glass frit (Scheme 6),
was used for this purpose. The synthesis of 6 was scaled up
from 0.6 mmol to 8.0 mmol (13-fold increase). To our delight,
the yield of this reaction increased to 85% in this scale-up
reaction with 1.95 g isolated product.
Finally, the reaction mechanism was considered. Sulfur
dioxide and the amine form Lewis acid–base adducts,
generating amidosulfinates in an equilibrium reaction after
deprotonation by an organic base (Scheme 7). Likewise,
Scheme 4. Sulfonamide substrate scope of different (hetero)arenes.
Grey background: isolated regioisomers. [a] Reaction conditions: arene
substrate (0.6 mmol, 0.1 m), morpholine (3 equiv.), DIPEA (4 equiv.),
SO2 (1.5 m), HFIP/MeCN=1:1, divided cell (glass frit), r.t., BDD
electrodes, j=12 mAcmÀ2, Q=3.5 F.
Thereupon, the amine substrate scope was investigated by
using 1,4-dimethoxybenzene as arene substrate (Scheme 5).
Several secondary amines were implemented, such as diiso-
butylamine, which provided sulfonamide 25 (63%). Compa-
rable yields ranging from 52–56% (26, 56%; 27, 55%; 28,
52%) were achieved with azepine, 2-methylpiperidine, and
tetrahydroisoquinoline. Dipropylamine and pyrrolidine pro-
vided slightly lower yields (29, 39%; 30, 37%). Primary
amines in general suffered from poor conversion. However,
benzylamine derivative 31 was isolated in 29% yield.
Sulfonamide 32 with l-proline methyl ester hydrochloride
as amine substrate was obtained in 24% yield (the lower yield
is potentially due to precipitation of the amine–SO2 complex
in the electrolyte). A list of substrates that were tried can be
retrieved from the Supporting Information.
Scheme 6. Scale-up reaction. Comparison between screening cell
(normal scale) and H-type glass cell (scale-up reaction).
Angew. Chem. Int. Ed. 2021, 60, 5056 –5062
ꢀ 2020 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH www.angewandte.org
5059

Angewandte
Communications
Chemie
Scheme 8. Cyclic voltammetry results. Black graph: morpholine
(0.3 m), DIPEA (0.4 m), SO2 (1.5 m), HFIP/MeCN=1:1.
functionalized electron-rich (hetero)arenes, SO2, and amines.
Highlights of this reaction are the use of inexpensive
electricity as “green” oxidant, as well as no necessity of any
additional supporting electrolyte. In situ formed amidosulfi-
nates perform a dual role as nucleophile and electrolyte. The
direct use of SO2 from a stock solution increases the atom
economy of this reaction in comparison to expensive SO2
surrogates such as DABSO. Regarding the mechanism of the
reaction, direct anodic oxidation of the (hetero)arene is
proposed to initiate the reaction based on the CV data. In
total, 36 different products were isolated, showing the full
potential of this novel reaction. Importantly, fluoro, chloro,
bromo, and iodo substituents are tolerated providing com-
plementarity to transition metal-catalyzed reactions. Scal-
ability of the reaction has been demonstrated by a 13-fold
scale-up.
Scheme 7. Postulated reaction mechanism.
Willis and co-workers considered this species as nucleophile
in their studies (Scheme 2).[6] The formation of an amine–SO2
complex is well described in the literature.[43] However,
complexes of triethylamine or DIPEA with SO2 are relatively
unstable.[31,44] Furthermore, the presence of HFIP could
À
weaken the S N interaction, so that DIPEA takes the role
as base in this reaction also leading to deprotonation of HFIP,
which is considered as additional supporting electrolyte[45]
and protonation probably also minimizes competitive oxida-
tion of DIPEA. In general, sterically hindered amine
Acknowledgements
À
substrates with weaker S N interaction, such as dibenzyl-
amine or 2,2,6,6-tetramethylpiperidine, did not perform well
in this reaction. We conclude that only amines with stronger
dative bonds to SO2 are eligible for this protocol.
The Carl Zeiss Stiftung is gratefully acknowledged for the
electrosynthesis network ELYSION. Financial support by
Deutsche Forschungsgemeinschaft (DFG: Wa1276/17-2) is
highly appreciated. S. Blum thanks Nicole Ehler for RP-
HPLC separation of regioisomers. Open access funding
enabled and organized by Projekt DEAL.
The proposed mechanism of the electrochemical sulfon-
amide synthesis proceeds via initial anodic oxidation of the
arene substrate to form the radical cation intermediate
(Scheme 7). Subsequent nucleophilic attack of the amidosul-
finate, followed by a second oxidation step, provides the
sulfonamide. As cathodic reaction, SO2 reduction was iden-
tified in our previous work.[28] Therefore, undivided cells are
ineligible due to anodic reoxidation of the reduced SO2
species resulting in significant lower overall current efficiency.
Additionally, cyclic voltammetry studies were executed in
order to support the proposal of the reaction mechanism
(Scheme 8). The oxidation potentials of 1,4-dimethoxyben-
zene (1.05 V) and 1,2,3-trimethoxybenzene (1.13 V) indicate
the initial anodic oxidation of the arene substrate when
comparing to the amidosulfinate species (black graph), which
determines the electrochemical potential window. The
increased oxidation potential of 6 (1.26 V) in comparison to
1,4-dimethoxybenzene is in accordance with the electron-
withdrawing sulfonamide substituent.
Conflict of interest
The authors declare no conflict of interest.
Keywords: electrochemistry · green chemistry · oxidation ·
radical reactions · sulfonamides
ˇ ´
´
´
[1] A. Tacic, V. Nikolic, L. Nikolic, I. Savic, Adv. Technol. 2017, 6,
58 – 71.
[2] H. Otten, J. Antimicrob. Chemother. 1986, 17, 689 – 690.
[3] S. Caddick, J. D. Wilden, D. B. Judd, J. Am. Chem. Soc. 2004, 126,
1024 – 1025.
[4] Critically Important Antimicrobials for Human Medicine, 6th re-
vision, World Health Organization, Geneva, 2019. Licence: CC
BY-NC-SA 3.0 IGO.
In conclusion, we have developed the first single-step
dehydrogenative synthesis of sulfonamides from non-pre-
5060 www.angewandte.org ꢀ 2020 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH
Angew. Chem. Int. Ed. 2021, 60, 5056 –5062

Angewandte
Communications
Chemie
[5] B. A. Caine, M. Bronzato, P. L. A. Popelier, Chem. Sci. 2019, 10,
4876 – 4878; k) F. Zhang, D. Zheng, L. Lai, J. Cheng, J. Sun, J.
6368 – 6381.
Wu, Org. Lett. 2018, 20, 1167 – 1170; l) W. Zhang, J. Xie, B. Rao,
M. Luo, J. Org. Chem. 2015, 80, 3504 – 3511; m) E. M. Alvarez,
M. B. Plutschack, F. Berger, T. Ritter, Org. Lett. 2020, 22, 4593 –
4596.
[6] Y. Chen, P. R. D. Murray, A. T. Davies, M. C. Willis, J. Am.
Chem. Soc. 2018, 140, 8781 – 8787.
[7] G. Laudadio, E. Barmpoutsis, C. Schotten, L. Struik, S. Govaerts,
D. L. Browne, T. Noꢀl, J. Am. Chem. Soc. 2019, 141, 5664 – 5668.
[8] C. T. Supuran, Molecules 2017, 22, 1642.
[31] E. J. Emmett, M. C. Willis, Asian J. Org. Chem. 2015, 4, 602 –
611.
[32] a) M. D. Kꢆrkꢆs, Chem. Soc. Rev. 2018, 47, 5786 – 5865; b) N.
Sauermann, T. H. Meyer, Y. Qiu, L. Ackermann, ACS Catal.
2018, 8, 7086 – 7103.
[9] M. A. Bhat, M. Imran, S. A. Khan, N. Siddiqui, Indian J. Pharm.
Sci. 2005, 67, 151 – 159.
[10] X. Dai, S. Kaluz, Y. Jiang, L. Shi, D. Mckinley, Y. Wang, B. Wang,
E. G. van Meir, C. Tan, Oncotarget 2017, 8, 99245 – 99260.
[11] a) G. De Simone, C. T. Supuran, Curr. Top. Med. Chem. 2007, 7,
879 – 884; b) M. al-Rashida, S. Hussain, M. Hamayoun, A. Altaf,
J. Iqbal, A. Di Fiore, Biomed. Res. Int. 2014, 2014, 162928.
[12] S. Shoaib Ahmad Shah, G. Rivera, M. Ashfaq, Mini-Rev. Med.
Chem. 2012, 13, 70 – 86.
[13] J. M. Ellis, J. W. Ross, C. I. Coleman, Formulary 2004, 39, 151.
[14] D. S. Wishart, Y. D. Feunang, A. C. Guo, E. J. Lo, A. Marcu, J. R.
Grant, T. Sajed, D. Johnson, C. Li, Z. Sayeeda, et al., Nucleic
Acids Res. 2018, 46, D1074-D1082.
[15] G. C. Roush, T. R. Holford, A. K. Guddati, Hypertension 2012,
59, 1110 – 1117.
[16] I. Goldstein, T. F. Lue, H. Padma-Nathan, R. C. Rosen, W. D.
Steers, P. A. Wicker, N. Engl. J. Med. 1998, 338, 1397 – 1404.
[17] W. Silverman, S. Locovei, G. Dahl, Am. J. Physiol. Cell Physiol.
2008, 295, C761 – C767.
[18] a) P. Devendar, G.-F. Yang, Topics Curr. Chem. 2017, 375, 82;
b) L. Clemens, J. Sulfur Chem. 2004, 25, 39 – 62.
[19] a) P. de Groote, P. G. Rouxhet, J. Devaux, P. Godard, Appl.
Spectrosc. 2001, 55, 877 – 887; b) P. de Groote, J. Devaux, P.
Godard, J. Polym. Sci. Part B 2002, 40, 2208 – 2218; c) D. Aelony,
Ind. Eng. Chem. Res. 1954, 46, 587 – 591.
[20] a) L. Wang, X. Pan, F. Wang, L. Yang, L. Liu, Dyes Pigm. 2008,
76, 636 – 645; b) H. E. Gaffer, M. R. Elgohary, H. A. Etman, S.
Shaaban, Pigment Resin Technol. 2017, 46, 210 – 217.
[21] a) S. I. Kang, Y. H. Bae, J. Controlled Release 2002, 80, 145 – 155;
b) W.-H. Chan, S. Y. Lam-Leung, C.-F. Ng, J. Ding, S. Xi,
Polymer 1995, 36, 4503 – 4508.
´
[33] a) P. Vogel, M. Turks, L. Bouchez, D. Markovic, A. Varela-
ꢇlvarez, J. ꢇ. Sordo, Acc. Chem. Res. 2007, 40, 931 – 942;
b) M. C. Willis, Phosphorus Sulfur Silicon Relat. Elem. 2019,
194, 654 – 657.
[34] a) S. Mçhle, M. Zirbes, E. Rodrigo, T. Gieshoff, A. Wiebe, S. R.
Waldvogel, Angew. Chem. Int. Ed. 2018, 57, 6018 – 6041; Angew.
Chem. 2018, 130, 6124 – 6149; b) A. Wiebe, T. Gieshoff, S. Mçhle,
E. Rodrigo, M. Zirbes, S. R. Waldvogel, Angew. Chem. Int. Ed.
2018, 57, 5594 – 5619; Angew. Chem. 2018, 130, 5694 – 5721.
[35] J. L. Rçckl, D. Pollok, R. Franke, S. R. Waldvogel, Acc. Chem.
Res. 2020, 53, 45 – 61.
[36] a) B. Gleede, T. Yamamoto, K. Nakahara, A. Botz, T. Graßl, R.
Neuber, T. Matthꢃe, Y. Einaga, W. Schuhmann, S. R. Waldvogel,
ChemElectroChem 2019, 6, 2771 – 2776; b) S. Lips, S. R. Wald-
vogel, ChemElectroChem 2019, 6, 1649 – 1660.
[37] a) B. Elsler, D. Schollmeyer, K. M. Dyballa, R. Franke, S. R.
Waldvogel, Angew. Chem. Int. Ed. 2014, 53, 5210 – 5213; Angew.
Chem. 2014, 126, 5311 – 5314; b) L. Schulz, S. R. Waldvogel,
Synlett 2019, 30, 275 – 286.
[38] a) S. B. Beil, T. Mꢂller, S. B. Sillart, P. Franzmann, A. Bomm, M.
Holtkamp, U. Karst, W. Schade, S. R. Waldvogel, Angew. Chem.
Int. Ed. 2018, 57, 2450 – 2454; Angew. Chem. 2018, 130, 2475 –
2479; b) T. Gieshoff, A. Kehl, D. Schollmeyer, K. D. Moeller,
S. R. Waldvogel, J. Am. Chem. Soc. 2017, 139, 12317 – 12324;
c) Y. Imada, J. L. Rçckl, A. Wiebe, T. Gieshoff, D. Schollmeyer,
K. Chiba, R. Franke, S. R. Waldvogel, Angew. Chem. Int. Ed.
2018, 57, 12136 – 12140; Angew. Chem. 2018, 130, 12312 – 12317;
d) S. Lips, D. Schollmeyer, R. Franke, S. R. Waldvogel, Angew.
Chem. Int. Ed. 2018, 57, 13325 – 13329; Angew. Chem. 2018, 130,
13509 – 13513; e) E. Rodrigo, S. R. Waldvogel, Chem. Sci. 2019,
10, 2044 – 2047; f) L. Schulz, M. Enders, B. Elsler, D. Scholl-
meyer, K. M. Dyballa, R. Franke, S. R. Waldvogel, Angew.
Chem. Int. Ed. 2017, 56, 4877 – 4881; Angew. Chem. 2017, 129,
4955 – 4959; g) S. R. Waldvogel, S. Mçhle, Angew. Chem. Int. Ed.
2015, 54, 6398 – 6399; Angew. Chem. 2015, 127, 6496 – 6497; h) A.
Wiebe, S. Lips, D. Schollmeyer, R. Franke, S. R. Waldvogel,
Angew. Chem. Int. Ed. 2017, 56, 14727 – 14731; Angew. Chem.
2017, 129, 14920 – 14925.
[22] M. Ashfaq, S. S. A. Shah, T. Najam, S. Shaheen, G. Rivera, Mini-
Rev. Med. Chem. 2013, 13, 160 – 170.
[23] C. Soriano-Correa, R. Esquivel, R. Sagar, Int. J. Quantum Chem.
2003, 94, 165 – 172.
[24] A. Gꢁmez-Palomino, J. Cornella, Angew. Chem. Int. Ed. 2019,
58, 18235 – 18239; Angew. Chem. 2019, 131, 18403 – 18407.
[25] Y. Fu, W. Zhu, X. Zhao, H. Hꢂgel, Z. Wu, Y. Su, Z. Du, D.
Huang, Y. Hu, Org. Biomol. Chem. 2014, 12, 4295 – 4299.
[26] T. Janosik, H. Shirani, N. Wahlstrçm, I. Malky, B. Stensland, J.
Bergman, Tetrahedron 2006, 62, 1699 – 1707.
[39] a) A. Wiebe, B. Riehl, S. Lips, R. Franke, S. R. Waldvogel, Sci.
Adv. 2017, 3, eaao3920; b) S. R. Waldvogel, S. Lips, M. Selt, B.
Riehl, C. J. Kampf, Chem. Rev. 2018, 118, 6706 – 6765.
[40] a) J. M. Freitas, T. d. C. Oliveira, R. A. A. Munoz, E. M. Richter,
Front. Chem. 2019, 7, 190; b) S. R. Waldvogel, S. Mentizi, A.
Kirste in Radicals in Synthesis III (Eds.: M. Heinrich, A.
Gansꢆuer), Springer, Berlin, Heidelberg, 2012, pp. 1 – 31.
[41] S. K. Sinha, T. Bhattacharya, D. Maiti, React. Chem. Eng. 2019,
4, 244 – 253.
[27] R. Pandya, T. Murashima, L. Tedeschi, A. G. M. Barrett, J. Org.
Chem. 2003, 68, 8274 – 8276.
[28] S. P. Blum, D. Schollmeyer, M. Turks, S. R. Waldvogel, Chem.
Eur. J. 2020, 26, 8358 – 8362.
[29] V. Magnꢃ, L. T. Ball, Chem. Eur. J. 2019, 25, 8903 – 8910.
[30] a) K. Bahrami, M. M. Khodaei, M. Soheilizad, J. Org. Chem.
2009, 74, 9287 – 9291; b) G. Y. Chung Leung, B. Ramalingam, G.
Loh, A. Chen, Org. Process Res. Dev. 2020, 24, 546 – 554; c) X.
Deng, N. S. Mani, Green Chem. 2006, 8, 835 – 838; d) N. Eid, I.
Karamꢃ, B. Andrioletti, Eur. J. Org. Chem. 2018, 5016 – 5022;
e) E. Flegeau, J. Harrison, M. Willis, Synlett 2015, 27, 101 – 105;
f) T. Liu, D. Zheng, Z. Li, J. Wu, Adv. Synth. Catal. 2017, 359,
2653 – 2659; g) S.-Y. Moon, J. Nam, K. Rathwell, W.-S. Kim, Org.
Lett. 2014, 16, 338 – 341; h) P. Mukherjee, C. P. Woroch, L.
Cleary, M. Rusznak, R. W. Franzese, M. R. Reese, J. W. Tucker,
J. M. Humphrey, S. M. Etuk, S. C. Kwan, et al., Org. Lett. 2018,
20, 3943 – 3947; i) P. K. Shyam, H.-Y. Jang, J. Org. Chem. 2017,
82, 1761 – 1767; j) H. Woolven, C. Gonzꢄlez-Rodrꢅguez, I.
Marco, A. L. Thompson, M. C. Willis, Org. Lett. 2011, 13,
[42] A. Biffis, P. Centomo, A. Del Zotto, M. Zecca, Chem. Rev. 2018,
118, 2249 – 2295.
[43] a) R. Ando, D. Matazo, P. Santos, J. Raman Spectrosc. 2010, 41,
771 – 775; b) A. Blaschette, H. Safari, Z. Naturforsch. B 1970, 25,
319 – 320; c) D. L. A. Faria, P. S. Santos, J. Raman Spectrosc.
1988, 19, 471 – 478; d) J.-G. Shim, Y. H. Jhon, J. H. Kim, K.-R.
Jang, J. Kim, Bull. Korean Chem. Soc. 2007, 28, 1609 – 1612;
e) N. M. Monezi, A. C. Borin, P. S. Santos, R. A. Ando, Spec-
trochim. Acta Part A 2017, 173, 462 – 467; f) J. J. Oh, K. W. Hillig,
R. L. Kuczkowski, J. Phys. Chem. 1991, 95, 7211 – 7216; g) J. J.
Angew. Chem. Int. Ed. 2021, 60, 5056 –5062
ꢀ 2020 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH www.angewandte.org
5061

Angewandte
Communications
Chemie
Oh, M. S. LaBarge, J. Matos, J. W. Kampf, K. W. Hillig, R. L.
Kuczkowski, J. Am. Chem. Soc. 1991, 113, 4732 – 4738.
[44] F. Eugene, B. Langlois, E. Laurent, Phosphorus Sulfur Relat.
Elem. 1993, 74, 377 – 378.
[45] J. L. Rçckl, M. Dçrr, S. R. Waldvogel, ChemElectroChem 2020,
7, 3686 – 3694.
Manuscript received: December 4, 2020
Accepted manuscript online: December 28, 2020
Version of record online: February 2, 2021
5062 www.angewandte.org ꢀ 2020 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH
Angew. Chem. Int. Ed. 2021, 60, 5056 –5062