Electroreductive Nickel-Catalyzed Thiolation: Efficient Cross-Electrophile Coupling for C?S Formation

Article abstract of DOI:10.1002/chem.202005449

Sulfur-containing molecules are of utmost topical importance towards the effective development of pharmaceuticals and functional materials. Herein, we present an efficient and mild electrochemical thiolation by cross-electrophile coupling of alkyl bromide

Full text of DOI:10.1002/chem.202005449

Communication
doi.org/10.1002/chem.202005449
Chemistry—A European Journal
&
Electrocatalysis
Electroreductive Nickel-Catalyzed Thiolation: Efficient Cross-
Electrophile Coupling for CÀS Formation
Nate W. J. Ang[a] and Lutz Ackermann*[a, b]
trast, the use of simple, bench-stable and odorless electrophilic
Abstract: Sulfur-containing molecules are of utmost topi-
thiosulfonates for the formation of CÀS bonds continues to be
cal importance towards the effective development of
underdeveloped.[5a–c,e,g,6] Cross-electrophile couplings have sur-
pharmaceuticals and functional materials. Herein, we pres-
faced as an impressive alternative to conventional cross-cou-
ent an efficient and mild electrochemical thiolation by
plings with preformed nucleophiles, providing an advantage in
cross-electrophile coupling of alkyl bromides with func-
terms of step-economy.[7] Notable examples for reductive
tionalized bench-stable thiosulfonates to access alkyl sul-
cross-electrophile thiolation include defluorinative reductive
fides with excellent efficacy and broad functional group
cross-coupling of gem-difluoroalkenes with thiosulfonates and
tolerance. Cyclic voltammetry and potentiostatic analysis
reductive thiolation of bromides (Scheme 1a)[5c,e] by using
were performed to elucidate mechanistic insights into this
electrocatalytic thiolation reaction.
The vast amount of resources that has been directed to re-
searches on nascent approaches for the formation of CÀS
bonds is caused by the influx of extensively useful sulfur-con-
taining drug scaffolds.[1] Alkyl sulfides have been recognized
for their unique importance in pharmaceuticals and organic
syntheses.[2] Traditionally, the formation of alkyl sulfides largely
required strong alkaline conditions that could hinder its use
with limited substrate scope and low yielding products.[3] Thus,
it is desirable to develop facile and yet efficient methods for
the CÀS formation. Transition-metal-catalyzed CÀS formations
have undoubtedly eased the syntheses of alkyl sulfides domi-
nated by precious metals, such as palladium, rhodium and
gold.[4] However, recently, 3d-transition metals have gained
major attention and are well-sought after due to their low tox-
icities and earth-abundant nature.[2c,4c,f,5] Thiols and their oxi-
dized derivatives are predominantly used as the coupling part-
ner. However, they are known to be highly toxic with foul-
Scheme 1. Electrochemical nickel-catalyzed cross-electrophile thiolation.
smelling odor and this impedes its functionality. In stark con-
[a] N. W. J. Ang, Prof. Dr. L. Ackermann
super-stoichiometric amounts of manganese as the chemical
Institut für Organische und Biomolekulare Chemie
Georg-August-Universität Gçttingen
Tammannstraße 2, 37077 Gçttingen (Germany)
E-mail: Lutz.Ackermann@chemie.uni-goettingen.de
reductant. Recently, electrocatalysis combined with 3d-metal
catalysis[8] has emerged as a powerful tool for sustainable mo-
lecular syntheses.[9] Pioneering studies for electrochemical thio-
Homepage: http://www.ackermann.chemie.uni-goettingen.de/
lation feature independent reports from Mei and Wang/Pan on
[b] Prof. Dr. L. Ackermann
redox-neutral nickel-catalyzed electrochemical CÀS bond for-
Wçhler Research Institute for Sustainable Chemistry (WISCh)
mation with substituted thiols as coupling partners
Georg-August-Universität Gçttingen
Tammannstraße 2, 37077 Gçttingen (Germany)
(Scheme 1b).[10] In addition to the impressive usage of electro-
synthesis for the formation of CÀS bonds, it is intriguing to un-
Supporting information and the ORCID identification number(s) for the
author(s) of this article can be found under:
https://doi.org/10.1002/chem.202005449.
ravel potent syntheses for thiolations that are mild and envi-
ronmentally friendly. Herein, we report on a nickel-catalyzed
cross-electrophile thiolation of alkyl bromides, featuring elec-
tricity as a mediator to access alkyl sulfides, which are
common structural motifs in numerous drug scaffolds
(Scheme 1c).[11]
ꢀ 2020 The Authors. Published by Wiley-VCH GmbH. This is an open access
article under the terms of the Creative Commons Attribution Non-Commer-
cial License, which permits use, distribution and reproduction in any
medium, provided the original work is properly cited and is not used for
commercial purposes.
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Table 1. Optimization of nickel-catalyzed electro-reductive thiolation.[a]
Entry
Deviation from
Yield[b]
standard conditions
1
2
3
4
–
86%
82%
67%
47%[c]
–
bathocuproine instead of 2,2’-bipyridine
neocuproine instead of 2,2’-bipyridine
NiCl2 (5.0 mol%)
5
Fe anode
6
Zn anode
–
7
Cu anode
–
8
9
10
11
12
13
Pt cathode
without catalyst
no electricity
Et4NOTs (0.5 equiv) as electrolyte
with IKA ElectraSyn 2.0
PhS-SPh (4a) instead of 2a
70%
37%[d]
–
51%
79%
–
[a] Undivided cell, 1a (0.250 mmol), 2a (0.275 mmol), NiBr2·diglyme
(5.0 mol%), 2,2’-bipyridine (7.5 mol%), solvent (5.0 mL), 258C, 3 h, Mg foil
electrode (3.0 mm ” 15 mm ” 0.2 mm), Ni foam electrode (10 mm ”
15 mm ” 1.0 mm), constant current electrolysis (CCE) at 5 mA with an
overall cell potential of 0.70–0.95 V. [b] Isolated yield. [c] 6 h reaction
time. [d] High potential was observed.
Scheme 2. Nickel-catalyzed electro-reductive thiolation of alkylbromide 1a
with substituted thiosulfonates 2. Faradaic yield given in parentheses.
the desired products 3af and 3ag in very good yields. More-
over, heterocyclic thiosulfonates (2h–j) were well tolerated and
furnished the thiolation products with high yield. The mild re-
action conditions were highly versatile as various thiosulfo-
nates were efficiently converted to the desired alkyl sulfide
product 3. Hence, we were intrigued to evaluate the per-
formance of the electro-catalysis on differently substituted bro-
mides (Scheme 3). To our delight, para-substituted electron-do-
nating groups, such as methyl 1b, methoxy 1c, both gave the
desired alkyl sulfide products with excellent yield. Electron-
withdrawing trifluoromethyl arene 1d also furnished the thio-
lated product with great yield, displaying no obvious preferen-
ces in terms of electronic influences. Various halogen-contain-
ing substrates (1e–f) gave the desired products (3ea–3ef) in a
highly chemoselective fashion. Synthetically useful cyclic 1,3-di-
oxolane substituted bromide 1g also underwent facile thiola-
tion to give excellent yield of the desired product. In addition,
ester-containing substrate 1h provided the desired alkyl sul-
fide product (3ha) with good yield. Various functional groups
such as terminal alkene (1i), sterically crowded 2-cyclohexyl
(1j), alkyl chloride (1k), and cyano (1l) were efficiently trans-
formed to products 3. The otherwise highly labile boronic
ester 1m remained intact in the electro-thiolation regime to
deliver the product (3ma). In addition, unprotected indole 1n
provided the desired product as well. Secondary bromides
(1o–p) were also successfully thiolated, albeit lower yields
were obtained.
We initiated our studies by optimizing the reaction condi-
tions (Table 1) for the envisioned electro-thiolation of alkyl hal-
ides with benzenethiosulfonates. Bidentate nitrogen-contain-
ing ligands such as bathocuproine and neocuproine failed to
give satisfactory yields (entries 2–3). Instead, the relatively inex-
pensive bipyridine outperformed them. Polar aprotic solvents,
such as DMF and DMA, performed decently for the electro-
thiolation (Table S-2).[12] Various anode and cathode materials
were tested for their efficacies (entries 5–8) but to no avail,
these includes platinum cathode which provided the desired
product with a lower yield. Control experiments (entries 9 and
10) substantiated the importance of electricity, and the essen-
tial role of the nickel catalyst for this cross-electrophile electro-
thiolation (Table S-3).[12] The use of electrolytes did not improve
the yield as the potential of the optimized reaction remained
stable throughout the entire course of electrolysis (entry 11).
Notably, the commercially available IKA ElectraSyn 2.0 was
used to exhibit the simplicity of the transformation, furnishing
product 3aa in comparable yield (entry 12). The use of diphen-
yl disulfide 4a did not lead to product formation (entry 13).
With the optimized reaction conditions in hand, we were
keen on exploring the substrate scope of the nickelaelectro-re-
ductive thiolation reaction. We embarked on testing the ro-
bustness with various substituted bench-stable thiosulfonates
(Scheme 2). Electron-donating groups such as para-substituted
methyl 2b, methoxy 2c, provided the product with great effi-
cacy. Halogen-containing substrates (2d–e) resulted in excel-
lent yield of the thiolated products (3ad and 3ae) without by-
product formation from CÀX cross-couplings. In addition, alkyl
thiosulfonates, such as benzyl 2 f and cyclohexyl 2g, delivered
In order to understand the mode of action for the nickel-
aelectro-catalyzed thiolation reaction with alkyl bromides 1, we
sought to investigate the mechanism in detail. First, radical
clock experiments also were performed with 6-bromo-1-
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Figure 1. Cyclic voltammetry (DMF, 0.1m nBu4NPF6, 100 mVsÀ1) with glassy
carbon as the working electrode. Cyclic voltammograms of different reaction
components.
systematically to disulfide due to their relative stability.[13] In
addition, a second reduction potential was found to be revers-
ible at Ep =À1.62 V vs. Ag/AgCl and this would then be as-
signed to the thiolate anion after a two-electrons transfer pro-
cess.[14] The nickel pre-catalyst exhibits an irreversible reduction
potential at Ep =À1.27 V vs. Ag/AgCl, which is lowered further
to a reversible reduction potential of Ep =À1.10 V vs. Ag/AgCl
by the ligation of the bipyridine ligand[12] for the reduction of
nickel(II) to nickel(I) analogous to previously reported observa-
tions.[15] Additional observations postulate that the ligated
nickel catalyst is found to undergo facile two electron reduc-
tion synergistically with the reduction of thiosulfonate. Further
mechanistic studies by means of potentiostatic reactions were
performed to illustrate the generation of thiyl radicals and the
subsequent disulfide formation through radical recombination
(Scheme 4). Potentiostatic reactions were conducted under the
otherwise standard reaction conditions.[16] As hypothesized,
the desired product was not formed at CPE=À0.70 V vs. Ag/
AgCl, but radical rebounded disulfide 4a was formed with
18% yield, likely due to an early first onset potential of the
thiosulfonate 2a at Eonset =À0.60 V vs. Ag/AgCl. In contrast, the
thiolated product 3aa was formed at CPE=À1.00 V vs. Ag/
AgCl, albeit with a considerable amount of by-product 4a,
plausibly by radical recombination. This observation is in good
agreement with our CV studies indicating possible formation
of thiyl radicals by initial reduction of substrate 2a. When the
Scheme 3. Nickel-catalyzed electro-reductive thiolation with bromides 1. Fa-
radaic yield given in parentheses.
hexene to illustrate the formation of primary alkyl radical
(Table 2).
Second, we elucidated various reduction potentials of the
substrates and catalyst by means of cyclic voltammetry (CV) as
disulfides were frequently present as by-product of the reac-
tion. The cathodic reduction of thiosulfonates was important
to determine the presence of an off-cycle pathway of this elec-
tro-catalysis. Cyclic voltammetry revealed that the reduction of
the bipyridine ligated nickel pre-catalyst is more facile than the
two-electron reduction of S-phenyl benzenethiosulfonate 2a
to the thiolate anion (Figure 1). The first reduction potential of
thiosulfonate 2a was shown to be irreversible at Ep =À0.91 V
vs. Ag/AgCl and this could plausibly be assigned to the forma-
tion of the thiyl radical. Thiyl radicals are known to recombine
Table 2. Radical Clock Experiment.
[a]
Entry
[Ni] (X mol%)
Ligand (Y mol%)
Yield[a]
3ia:3ia’
1
2
2.50
5.00
3.75
7.50
69%
96%
14:1
>20:1
[a] Yield and ratio determined by 1H NMR spectroscopy with 1,3,5-
trimethoxybenzene as internal standard.
Scheme 4. Potentiostatic studies.
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Chemistry—A European Journal
potential was higher than the second reduction potential of
substrate 2a at CPE=À1.80 V vs. Ag/AgCl, the desired thiolat-
ed product 3aa was obtained with 53% yield, while by-pro-
duct 4a was formed with 44% yield.
Conflict of interest
The authors declare no conflict of interest.
A plausible catalytic cycle is proposed based on the ob-
tained results (Scheme 5).[5e,f,17] Initially, oxidative addition of 2
onto the active nickel(0) catalyst I occurs.[8b,18] This formed in-
termediate II then combines with an alkyl radical formed in
situ to give a nickel(III) complex. The complex III undergoes re-
ductive elimination to provide the thiolation product 3
through a CÀS bond formation. Nickel(I) complex IV would
subsequently react with another molecule of alkyl bromide re-
generating the alkyl radical and form nickel(II) intermediate V.
This then undergoes cathodic reduction to reform the active
catalyst.[19]
Keywords: cross-electrophile coupling · electrosynthesis
nickel · reductive · thiolation
·
[1] a) J.-M. Wang, G.-Z. Ding, L. Fang, J.-G. Dai, S.-S. Yu, Y.-H. Wang, X.-G.
Chen, S.-G. Ma, J. Qu, S. Xu, D. Du, J. Nat. Prod. 2010, 73, 1240–1249;
b) H. Guo, B. Sun, H. Gao, X. Chen, S. Liu, X. Yao, X. Liu, Y. Che, J. Nat.
Prod. 2009, 72, 2115–2119; c) M. E. Thase, W. Macfadden, R. H. Weisler,
W. Chang, B. Paulsson, A. Khan, J. R. Calabrese, J. Clin. Psychopharmacol.
2006, 26, 600–609; d) S. C. Piscitelli, T. F. Goss, J. H. Wilton, D. T.
D’Andrea, H. Goldstein, J. J. Schentag, Antimicrob. Agents Chemother.
1991, 35, 1765–1771; e) L. P. Garrod, Br. Med. J. 1960, 2, 1695–1696;
f) L. P. Garrod, Br. Med. J. 1960, 1, 527–529.
[2] a) N. Wang, P. Saidhareddy, X. Jiang, Nat. Prod. Rep. 2020, 37, 246–275;
b) K. L. Dunbar, D. H. Scharf, A. Litomska, C. Hertweck, Chem. Rev. 2017,
117, 5521–5577; c) H. Liu, X. Jiang, Chem. Asian J. 2013, 8, 2546–2563;
d) F.-Z. Wang, Z. Huang, X.-F. Shi, Y.-C. Chen, W.-M. Zhang, X.-P. Tian, J.
Li, S. Zhang, Bioorg. Med. Chem. Lett. 2012, 22, 7265–7267; e) C.-S.
Jiang, W. E. G. Müller, H. C. Schrçder, Y.-W. Guo, Chem. Rev. 2012, 112,
2179–2207; f) F. C. Odds, C. E. Webster, A. B. Abbott, J. Antimicrob. Che-
mother. 1984, 14, 105–114.
[3] H. Gilman, N. J. Beaber, J. Am. Chem. Soc. 1925, 47, 1449–1451.
[4] a) Z. Lian, B. N. Bhawal, P. Yu, B. Morandi, Science 2017, 356, 1059–
1063; b) S. D. Timpa, C. J. Pell, O. V. Ozerov, J. Am. Chem. Soc. 2014, 136,
14772–14779; c) C.-F. Lee, Y.-C. Liu, S. S. Badsara, Chem. Asian J. 2014, 9,
706–722; d) C.-S. Lai, H.-L. Kao, Y.-J. Wang, C.-F. Lee, Tetrahedron Lett.
2012, 53, 4365–4367; e) M. Sayah, M. G. Organ, Chem. Eur. J. 2011, 17,
11719–11722; f) I. P. Beletskaya, V. P. Ananikov, Chem. Rev. 2011, 111,
1596–1636; g) M. Jean, J. Renault, P. van de Weghe, N. Asao, Tetrahe-
dron Lett. 2010, 51, 378–381; h) M. Arisawa, T. Suzuki, T. Ishikawa, M. Ya-
maguchi, J. Am. Chem. Soc. 2008, 130, 12214–12215; i) N. Morita, N.
Krause, Angew. Chem. Int. Ed. 2006, 45, 1897–1899; Angew. Chem.
2006, 118, 1930–1933; j) M. A. Fernµndez-Rodríguez, Q. Shen, J. F. Hart-
wig, J. Am. Chem. Soc. 2006, 128, 2180–2181; k) T. Kondo, T.-A. Mitsudo,
Chem. Rev. 2000, 100, 3205–3220.
[5] a) P. Xu, Y.-M. Zhu, X.-J. Li, F. Wang, S.-Y. Wang, S.-J. Ji, Adv. Synth. Catal.
2019, 361, 4909–4913; b) J. Li, S.-Y. Wang, S.-J. Ji, J. Org. Chem. 2019,
84, 16147–16156; c) J. Li, W. Rao, S.-Y. Wang, S.-J. Ji, J. Org. Chem. 2019,
84, 11542–11552; d) G. Kibriya, S. Mondal, A. Hajra, Org. Lett. 2018, 20,
7740–7743; e) Y. Fang, T. Rogge, L. Ackermann, S.-Y. Wang, S.-J. Ji, Nat.
Commun. 2018, 9, 2240; f) M. S. Oderinde, M. Frenette, D. W. Robbins, B.
Aquila, J. W. Johannes, J. Am. Chem. Soc. 2016, 138, 1760–1763; g) P.
Mampuys, Y. Zhu, T. Vlaar, E. Ruijter, R. V. A. Orru, B. U. W. Maes, Angew.
Chem. Int. Ed. 2014, 53, 12849–12854; Angew. Chem. 2014, 126, 13063–
13068; h) T.-J. Liu, C.-L. Yi, C.-C. Chan, C.-F. Lee, Chem. Asian J. 2013, 8,
1029–1034; i) M.-T. Lan, W.-Y. Wu, S.-H. Huang, K.-L. Luo, F.-Y. Tsai, RSC
Adv. 2011, 1, 1751–1755; j) J.-R. Wu, C.-H. Lin, C.-F. Lee, Chem. Commun.
2009, 4450–4452; k) A. Correa, M. Carril, C. Bolm, Angew. Chem. Int. Ed.
2008, 47, 2880–2883; Angew. Chem. 2008, 120, 2922–2925; l) Y.-C.
Wong, T. T. Jayanth, C.-H. Cheng, Org. Lett. 2006, 8, 5613–5616; m) O.
Baldovino-Pantaleón, S. Hernµndez-Ortega, D. Morales-Morales, Adv.
Synth. Catal. 2006, 348, 236–242; n) N. Taniguchi, J. Org. Chem. 2004,
69, 6904–6906; o) F. Y. Kwong, S. L. Buchwald, Org. Lett. 2002, 4, 3517–
3520.
[6] a) W. Wang, X. Peng, F. Wei, C.-H. Tung, Z. Xu, Angew. Chem. Int. Ed.
2016, 55, 649–653; Angew. Chem. 2016, 128, 659–663; b) F. F. Fleming,
S. Gudipati, V. A. Vu, R. J. Mycka, P. Knochel, Org. Lett. 2007, 9, 4507–
4509; c) A. H. Stoll, A. Krasovskiy, P. Knochel, Angew. Chem. Int. Ed. 2006,
45, 606–609; Angew. Chem. 2006, 118, 621–623; d) G. Palumbo, C. Fer-
reri, C. D’Ambrosio, R. Caputo, Phosphorus Sulfur 1984, 19, 235–238.
[7] a) B. L. Truesdell, T. B. Hamby, C. S. Sevov, J. Am. Chem. Soc. 2020, 142,
5884–5893; b) G. S. Kumar, A. Peshkov, A. Brzozowska, P. Nikolaienko, C.
Zhu, M. Rueping, Angew. Chem. Int. Ed. 2020, 59, 6513–6519; Angew.
Chem. 2020, 132, 6575–6581; c) K.-J. Jiao, D. Liu, H.-X. Ma, H. Qiu, P.
Fang, T.-S. Mei, Angew. Chem. Int. Ed. 2020, 59, 6520–6524; Angew.
Scheme 5. Plausible catalytic cycle.
In summary, we have developed an efficient and robust nick-
elaelectro-catalyzed strategy for the cross-electrophile electro-
coupling of alkyl bromides and thiosulfonates to access alkyl
sulfides through CÀS bond formation under ambient condi-
tions, devoid of harsh chemical reductants. The mild electro-
thiolation provided a broad and versatile substrate scope with
excellent yields. Cyclic voltammetry and potentiostatic investi-
gations provided detailed mechanistic insights into the reac-
tion mechanism.
Acknowledgements
Generous support by the DFG (Gottfried-Wilhelm-Leibniz
award to LA) is gratefully acknowledged. Open access funding
enabled and organized by Projekt DEAL.
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Chem. 2020, 132, 6582–6586; d) N. W. J. Ang, J. C. A. Oliveira, L. Acker-
mann, Angew. Chem. Int. Ed. 2020, 59, 12842–12847; Angew. Chem.
2020, 132, 12942–12947; e) E. L. Lucas, E. R. Jarvo, Nat. Rev. Chem.
2017, 1, 0065; f) D. J. Weix, Acc. Chem. Res. 2015, 48, 1767–1775; g) T.
Moragas, A. Correa, R. Martin, Chem. Eur. J. 2014, 20, 8242–8258;
h) C. E. I. Knappke, S. Grupe, D. Gärtner, M. Corpet, C. Gosmini, A. Jacobi
von Wangelin, Chem. Eur. J. 2014, 20, 6828–6842.
novets, A. Tolmachev, ACS Comb. Sci. 2015, 17, 348–354; d) H. L. Hol-
land, Nat. Prod. Rep. 2001, 18, 171–181.
[12] D. L. Davies, S. A. Macgregor, A. I. Poblador-Bahamonde, Dalton Trans.
2010, 39, 10520–10527.
[13] a) C. Schçneich, Molecules 2019, 24, 4357; b) F. DØn›s, M. Pichowicz, G.
Povie, P. Renaud, Chem. Rev. 2014, 114, 2587–2693; c) R. P. Steer, B. L.
Kalra, A. R. Knight, J. Phys. Chem. 1967, 71, 783–784.
[8] a) S.-K. Zhang, J. Struwe, L. Hu, L. Ackermann, Angew. Chem. Int. Ed.
2020, 59, 3178–3183; Angew. Chem. 2020, 132, 3204–3209; b) S.-K.
Zhang, R. C. Samanta, A. Del Vecchio, L. Ackermann, Chem. Eur. J. 2020,
26, 10936–10947; c) J. C. Siu, N. Fu, S. Lin, Acc. Chem. Res. 2020, 53,
547–560; d) R. C. Samanta, T. H. Meyer, I. Siewert, L. Ackermann, Chem.
Sci. 2020, 11, 8657–8670; e) K.-J. Jiao, Y.-K. Xing, Q.-L. Yang, H. Qiu, T.-S.
Mei, Acc. Chem. Res. 2020, 53, 300–310; f) C. Zhu, M. Stangier, J. C. A.
Oliveira, L. Massignan, L. Ackermann, Chem. Eur. J. 2019, 25, 16382–
16389; g) T. H. Meyer, J. C. A. Oliveira, S. C. Sau, N. W. J. Ang, L. Acker-
mann, ACS Catal. 2018, 8, 9140–9147.
[9] a) J. L. Rçckl, D. Pollok, R. Franke, S. R. Waldvogel, Acc. Chem. Res. 2020,
53, 45–61; b) S. D. Minteer, P. Baran, Acc. Chem. Res. 2020, 53, 545–546;
c) L. Ackermann, Acc. Chem. Res. 2020, 53, 84–104; d) H. Wang, X. Gao,
Z. Lv, T. Abdelilah, A. Lei, Chem. Rev. 2019, 119, 6769–6787; e) N. Shida,
Y. Zhou, S. Inagi, Acc. Chem. Res. 2019, 52, 2598–2608; f) M. Elsherbini,
T. Wirth, Acc. Chem. Res. 2019, 52, 3287–3296; g) N. Sauermann, T. H.
Meyer, Y. Qiu, L. Ackermann, ACS Catal. 2018, 8, 7086–7103; h) N. Sau-
ermann, T. H. Meyer, L. Ackermann, Chem. Eur. J. 2018, 24, 16209–
16217; i) K. D. Moeller, Chem. Rev. 2018, 118, 4817–4833; j) Y. Jiang, K.
Xu, C. Zeng, Chem. Rev. 2018, 118, 4485–4540; k) N. Fu, G. S. Sauer, S.
Lin, Nat. Protoc. 2018, 13, 1725–1743; l) M. Yan, Y. Kawamata, P. S.
Baran, Chem. Rev. 2017, 117, 13230–13319; m) E. J. Horn, B. R. Rosen,
P. S. Baran, ACS Cent. Sci. 2016, 2, 302–308; n) R. Francke, R. D. Little,
Chem. Soc. Rev. 2014, 43, 2492–2521; o) J. B. Sperry, D. L. Wright, Chem.
[14] a) G. Roos, F. De Proft, P. Geerlings, Chem. Eur. J. 2013, 19, 5050–5060;
b) D. A. Armstrong, Q. Sun, R. H. Schuler, J. Phys. Chem. 1996, 100,
9892–9899; c) P. S. Surdhar, D. A. Armstrong, J. Phys. Chem. 1987, 91,
6532–6537; d) P. Surdhar, D. A. Armstrong, J. Phys. Chem. 1986, 90,
5915–5917.
[15] a) Y. Kawamata, J. C. Vantourout, D. P. Hickey, P. Bai, L. Chen, Q. Hou, W.
Qiao, K. Barman, M. A. Edwards, A. F. Garrido-Castro, J. N. deGruyter, H.
Nakamura, K. Knouse, C. Qin, K. J. Clay, D. Bao, C. Li, J. T. Starr, C. Garcia-
Irizarry, N. Sach, H. S. White, M. Neurock, S. D. Minteer, P. S. Baran, J. Am.
Chem. Soc. 2019, 141, 6392–6402; b) M. Durandetti, J. Maddaluno, in
Encyclopedia of Reagents for Organic Synthesis, Wiley, 2014, pp. 1–6;
c) I. Zilbermann, E. Maimon, H. Cohen, D. Meyerstein, Chem. Rev. 2005,
105, 2609–2626; d) A. G. Lappin, A. McAuley, Adv. Inorg. Chem. 1988,
32, 241–295.
[16] a) L. Muchez, D. E. De Vos, M. Kim, ACS Sustainable Chem. Eng. 2019, 7,
15860–15864; b) C. Li, X. Tong, P. Yu, W. Du, J. Wu, H. Rao, Z. M. Wang,
J. Mater. Chem. A 2019, 7, 16622–16642; c) B. Shan, R. Schmehl, J. Phys.
Chem. A 2014, 118, 10400–10406; d) S. Maity, N. Zheng, Synlett 2012,
23, 1851–1856; e) R. D. Richardson, E. J. Holland, B. K. Carpenter, Nat.
Chem. 2011, 3, 301–303; f) D. R. Prasad, M. Z. Hoffman, J. Phys. Chem.
1984, 88, 5660–5665.
[17] a) G. T. Venkanna, H. D. Arman, Z. J. Tonzetich, ACS Catal. 2014, 4, 2941–
2950; b) S. Biswas, D. J. Weix, J. Am. Chem. Soc. 2013, 135, 16192–
16197.
Soc. Rev. 2006, 35, 605–621; p) T. Shono, Tetrahedron 1984, 40, 811 – [18] D. Vasudevan, Russ. J. Electrochem. 2005, 41, 310–314.
850.
[19] a) V. B. Mostardeiro, M. C. Dilelio, T. S. Kaufman, C. C. Silveira, RSC Adv.
2020, 10, 482–491; b) E. Dmitrieva, X. Yu, H. Hartmann, Electrochem.
Commun. 2020, 114, 106706; c) B. Janhsen, C. G. Daniliuc, A. Studer,
Chem. Sci. 2017, 8, 3547–3553.
[10] a) Y. Wang, L. Deng, X. Wang, Z. Wu, Y. Wang, Y. Pan, ACS Catal. 2019, 9,
1630–1634; b) D. Liu, H.-X. Ma, P. Fang, T.-S. Mei, Angew. Chem. Int. Ed.
2019, 58, 5033–5037; Angew. Chem. 2019, 131, 5087–5091.
[11] a) A. S. Surur, L. Schulig, A. Link, Arch. Pharm. Chem. Life Sci. 2019, 352,
e1800248; b) M. Feng, B. Tang, S. H. Liang, X. Jiang, Curr. Top. Med.
Chem. 2016, 16, 1200–1216; c) A. V. Bogolubsky, Y. S. Moroz, P. K. My-
khailiuk, E. N. Ostapchuk, A. V. Rudnichenko, Y. V. Dmytriv, A. N. Bondar,
O. A. Zaporozhets, S. E. Pipko, R. A. Doroschuk, L. N. Babichenko, A. I. Ko-
Manuscript received: December 23, 2020
Accepted manuscript online: December 28, 2020
Version of record online: February 15, 2021
Chem. Eur. J. 2021, 27, 4883 –4887
www.chemeurj.org
4887
ꢀ 2020 The Authors. Published by Wiley-VCH GmbH