Rhoda-Electrocatalyzed Bimetallic C?H Oxygenation by Weak O-Coordination

Article abstract of DOI:10.1002/anie.202017359

Rhodium-electrocatalyzed arene C?H oxygenation by weakly O-coordinating amides and ketones have been established by bimetallic electrocatalysis. Likewise, diverse dihydrooxazinones were selectively accessed by the judicious choice of current, enabling twofold C?H functionalization. Detailed mechanistic studies by experiment, mass spectroscopy and cyclovoltammetric analysis provided support for an unprecedented electrooxidation-induced C?H activation by a bimetallic rhodium catalysis manifold.

Full text of DOI:10.1002/anie.202017359

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How to cite:
International Edition: doi.org/10.1002/anie.202017359
German Edition: doi.org/10.1002/ange.202017359
À
C H Activation
À
Rhoda-Electrocatalyzed Bimetallic C H Oxygenation by Weak O-
Coordination
Xuefeng Tan+, Leonardo Massignan+, Xiaoyan Hou, Johanna Frey, Jo¼o C. A. Oliveira,
Masoom Nasiha Hussain, and Lutz Ackermann*
In memory of Professor Jean-Michel Savꢀant
À
Abstract: Rhodium-electrocatalyzed arene C H oxygenation
by weakly O-coordinating amides and ketones have been
established by bimetallic electrocatalysis. Likewise, diverse
dihydrooxazinones were selectively accessed by the judicious
amounts of strong chemical oxidants, such as (diacetoxyio-
do)benzene and K2S2O8, are required, which leads to un-
desired byproducts.
Electrochemical synthesis has undergone a renaissance in
recent years towards environmentally-benign organic syn-
thesis.[8] Significant recent impetus was gained by the merger
À
choice of current, enabling twofold C H functionalization.
Detailed mechanistic studies by experiment, mass spectroscopy
and cyclovoltammetric analysis provided support for an
À
of electrocatalysis with oxidative C H activation, thus
unprecedented electrooxidation-induced C H activation by
avoiding the use of toxic and expensive metal oxidants.[9]
À
À
a bimetallic rhodium catalysis manifold.
Although transition metal-catalyzed electrochemically C H
oxygenation have been recently realized,[10] this mostly
required strong N-coordination, such as bidentate quinolinyl
amides or pyridines, while the very recently devised ruthe-
nium catalysis needed rather costly aryl iodides as additional
redox mediators, jeopardizing the inherent atom-economy.[10a]
In contrast, the redox direct—mediator-free—oxidation of
homogeneous metal oxygenation catalysts at the anode
Introduction
À
During the past decade, transition metal-catalyzed C H
activation has been recognized as a transformative tool in
molecular syntheses.[1] Phenols featuring an ortho-substituted
carbonyl group constitute important structural motifs of
a diversity of bioactive molecules, ranging from natural
products to drugs molecules.[2] Transition metal-catalyzed
surface typically called for a divided cell setup.[10e–g] Within
[11]
À
our program on electrochemical C H activation, we have
À
C H activation by weak chelation assistance provides
now devised mechanistically-distinct rhoda-electrocatalyzed
a straightforward access to the assembly of phenols.[3]
Pioneering studies with palladium catalysis were accom-
plished by Dong[4] and Rao.[5] In the same year, our group
C H oxygenations of weakly-O-coordinating amides and
À
ketones (Figure 1). Salient features of our findings include
1) undivided cell without redox mediator, 2) room temper-
ature oxygenations, 3) electricity in lieu of strong oxidants,
À
reported sustainable ruthenium-catalyzed C H oxygenations
with a diverse range of weakly coordinating groups.[6] In
addition, considerable efforts have been devoted to the
development of different metal catalysts, along with various
oxidants.[7] Despite indisputable advances, stoichiometric
4) high Faraday efficiency, 5) twofold electrochemical C H
À
functionalization towards dihydrooxazinones,[12] and 6) de-
tailed mechanistic support for a bimetallic electrocatalysis
manifold.
[*] Dr. X. Tan,[+] L. Massignan,[+] X. Hou, Dr. J. Frey, Dr. J. C. A. Oliveira,
M. N. Hussain, Prof. Dr. L. Ackermann
Institut fꢀr Organische und Biomolekulare Chemie, Georg-August-
Universitꢁt Gçttingen
Tammannstraße 2, 37077 Gçttingen (Germany)
E-mail: Lutz.Ackermann@chemie.uni-goettingen.de
Prof. Dr. L. Ackermann
Wçhler Research Institute for Sustainable Chemistry, Georg-August-
Universitꢁt Gçttingen
Tammannstraße 2, 37077 Gçttingen (Germany)
[+] These authors contributed equally to this work.
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.202017359.
À
Figure 1. Rhoda-electrocatalyzed C H oxygenation.
ꢂ 2021 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
License, which permits use, distribution and reproduction in any
medium, provided the original work is properly cited and is not used
for commercial purposes.
Results and Discussion
At the outset of our studies, various reaction conditions
were explored for the envisioned redox-mediator-free, rhoda-
À
electrocatalyzed C H oxygenation of 1a in an operationally
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[a]
À
Table 1: Optimization of the rhoda-electrocatalyzed C H oxygenation.
Entry
Electrolyte
TFA/TFAA I [mA] t [h] T [8C] Yield [%]
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
CF3COONa
LiClO4
3:1
3:1
3:1
3:1
1:1
1:1
4
4
4
4
4
4
4
4
0
4
4
4
2
2
4
2
16
16
16
16
16
16
16
16
16
16
16
8
50
50
50
50
50
RT
RT
RT
RT
RT
RT
RT
RT
RT
50
RT
trace
24
22
28
42
nBu4NBF4
nBu4NPF6
nBu4NPF6
nBu4NPF6
nBu4NPF6
nBu4NPF6
nBu4NPF6
nBu4NPF6
nBu4NPF6
54
52
1:2
1:3[b]
1:1
trace
ND
trace[c]
57[d]
76[d]
82[d]
ND[f]
28[g]
52[h]
1:1
1:1
1:20
1:20
1:20
3:1
[e]
TFA·NEt3
[e]
TFA·NEt3
15
15
16
15
[e]
TFA·NEt3
nBu4NPF6
[e]
TFA·NEt3
1:20
[a] 1a (0.5 mmol), [Rh(OAc)2]2 (2.5 mol%), electrolyte (0.10 M), TFA/
TFAA, GF anode (10 mm ꢃ 10 mm ꢃ 6 mm), Pt cathode (10 mm ꢃ
15 mm ꢃ 0.125 mm). [b] Poor conductivity due to poor solubility of
electrolyte. [c] Without [Rh(OAc)2]2. [d] Under N2. [e] TFA·NEt3 (0.33 M).
[f] [RhCp*Cl2]2 or RhCl3.3H2O instead of [Rh(OAc)2]2 as the catalyst.
[g] Ru(OAc)2(p-cymene) (5 mol%) as the catalyst. [h] [Rh(OPiv)2]2 as the
catalyst. Piv=pivalate.
simple undivided cell equipped with a graphite felt (GF)
anode and a platinum cathode (Table 1 and Table S1 in the
Supporting Information).[13] Preliminary experimentation in-
dicated that nBu4NPF6 was the optimal additive (Table 1,
Entries 1–4). Further studies revealed that the reaction was
viable at ambient temperature (Entries 5–6) in a solvent
mixture of trifluoroacetic acid (TFA) and trifluoroacetic
anhydride (TFAA) (1:1) (Entries 6–8). Control experiments
showed that both the rhodium catalyst and electricity were
essential (Entries 9–11). During the optimization, we found
that NEt3 could significantly improve the conductivity
(Table S1). Thus we employed easily available TFA·NEt3 salt
(Entry 12),[14] enabling the use of a solvent mixture TFA/
TFAA (1:20) without solubility or conductivity problems
(Entries 12–13 vs. Entry 8). Here, the highest yield of 82%
was obtained with 2 mA (Entry 13). Interestingly, while
[Rh(OAc)2]2 showed high catalytic efficacy, the commonly
used [RhCp*Cl2]2 or RhCl3·3H2O provided unsatisfactory
results (Entry 14).
À
Scheme 1. Rhoda-electrocatalyzed C H oxygenation of amides 1 and 3.
rhoda-electrocatalysis was not limited to Weinreb amides 1.
Indeed, differently substituted amides 3a–m were also
efficiently converted into the corresponding oxygenated
amides 4a–m with remarkable catalytic efficiency (Sche-
me 1b).
With the optimized reaction conditions in hand, we next
examined the viable substrate scope of the rhodium-catalyzed
The outstanding robustness of the rhoda-electrocatalyzed
À
À
electrochemical C H oxygenation with various weakly coor-
C H oxygenation was further highlighted by its ability to
transform more challenging ketones 5 (Scheme 2).
dinating Weinreb amides 1 (Scheme 1a). Electron-rich as well
as electron-deficient Weinreb amides 1a–1p were amenable
to the rhodium-catalyzed electrochemical catalysis. Notably,
a diverse array of valuable functional groups, including ester
(2 f), halogen (2g–2j) and ketone (2k) groups, were tolerated
by the electrocatalysis, highlighting a notable potential for
further late-stage diversification. It is noteworthy that the
During our optimization studies, small amounts of N-
demethylation product 7a could often be isolated (Sche-
me 3a). Hence, we rationalized that it was formed through
À
a cascade C H oxygenation, along with Shono-type oxidation
to generate Int2. Further experimentation at Q ꢀ 4 FmolÀ1
revealed small amounts of an interesting dihydrooxazinone
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path). With the optimized reaction conditions, we explored
the substrate scope of the rhoda-electrocatalyzed cascade
reaction with diverse amides 1 and 3 to assemble various
dihydrooxazinones 8 and 9 (Scheme 3b). The tolerance of
ester (8 f) and halogen (8g, 8i, 8p, 9d–e, 9h) substitute
provides an invaluable asset in terms of late-stage modifica-
tions.
À
Scheme 2. Rhoda-electrocatalyzed C H oxygenation of ketones 5.
Scheme 4. Application to the synthesis of the analogous fragments of
Promysalin.
Promysalin is a Pseudomonad secondary metabolite that
exhibits narrow-spectrum antibacterial activity, originally
isolated from the rhizosphere (Scheme 4a).[15] In 2016, Wuest
reported the total synthesis of Promysalin analogues.[15b] The
key proline-salicylate fragment in Promysalin inspired us to
À
apply our rhoda-electrocatalyzed C H oxygenation to the
synthesis of various substituted proline-salicylates (4n–p)
without any protection and deprotection of the phenol motif
(Scheme 4b). Next, we studied the efficiency of the catalysis
with bromo analog 3p through the gram-scale synthesis with
only 0.5 mol% of [Rh(OAc)2]2 with a turnover number of 166
based on the rhodium-dimer, along with the solvent TFAA
being recovered by simple distillation, highlighting the
practical potential of this catalysis (Scheme 4c).
Given the versatility of the redox mediator-free electro-
À
chemical C H oxygenation, we became attracted to probing
its mode of action. Reactions conducted with isotopically
Scheme 3. Rhoda-electrocatalyzed cascade reaction for the synthesis of
dihydrooxazinones.
labeled [D]1-TFA did not lead to any H/D scrambling.[13]
À
Kinetic studies provided strong support for a fast C H
8a. Through rational design of the work up process with NEt3
as non-nucleophilic base, Int2 could be exclusively converted
to the valuable dihydrooxazinone[12] 8a (Scheme 3a, blue
metalation with a minor kinetic isotope effect (KIE) of kH/kD
ꢁ 1.1 (Scheme 5a). Then, we explored the current depend-
ence of the performance within a range from 2.0 to 5.0 mA,
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electrochemical catalysis (Scheme 6a). Mass spectroscopy
studies revealed a rapid -OAc/-OTFA exchange in the solvent
mixture TFA/TFAA (1:1), while in TFA/TFAA (1:20) this
exchange was slow,[13] which may be caused by the low
concentration of available TFA. These observations are
matched with the low catalytic activity in TFA/TFAA (1:1)
(Table 1), suggesting the ligand exchange to be harmful to the
catalyst activity. While stepwise electrochemical oxygenation
À
delineated an oxidation-induced C H activation and oxygen-
ation, mass spectroscopic analysis of the electrolyzed mixture
showed a plausible active intermediate [Rh(OAc)2(OTFA)]2,
highlighting the dimeric form of the catalyst (Scheme 6b).
This was further experimentally supported by the inactivity of
the monomeric Rh(OAc)3 (Scheme 6c).
Furthermore, we probed an electrochemical oxidation-
À
induced C H activation by means of cyclovoltammetric
analysis (Figure 2). First, the oxidation potential of amide
Scheme 5. Key mechanistic experiments.
being indicative of a turnover-limiting electron transfer step
in the current region of 2.0–4.0 mA (Scheme 5b). Beyond
4.0 mA the reaction rate did not increase significantly, being
suggestive of a switch in the turnover-limiting step.
Next, we turned our attention to investigate the ligand
exchange effect at rhodium. Somewhat surprisingly, [Rh-
(OTFA)2]2 did not show any catalytic reactivity for this
Figure 2. Cyclic voltammetry measurements in TFA/TFAA with 0.15 M
TFA·NEt3 and 5 mM substrate at RT with a scan rate of 100 mVsÀ1
:
(a) in TFA/TFAA (1:1); (b) dark, [Rh(OAc)2]2 in TFA/TFAA (1:20),
stirred 10 min, poor solubility; blue, [Rh(OAc)2]2 in TFA/TFAA (1:1),
measured at stirring 5, 30 and 60 min; red, [Rh(OTFA)2]2 in TFA/TFAA
(1:1).
Scheme 6. Mechanistic studies on rhoda-electrocatalyzed oxygenation.
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1a was higher than [Rh(OAc)2]2 in TFA/TFAA (1:1),
À
suggesting an oxidation-induced C H activation regime
(Figure 2a). In TFA/TFAA (1:20), [Rh(OAc)2]2 featured an
onset potential of Eonset = 0.8 V vs. Ag/AgCl with low current,
due to the poor solubility of [Rh(OAc)2]2 (Figure 2b, dark). In
TFA/TFAA (1:1), the oxidation peak shifts to higher oxida-
tion potentials, this shift is likely caused by gradually
-OAc/-OTFA ligand exchange, implying the more -OTFA
substituents on rhodium, the higher oxidation potential
exhibited (Figure 2b, blue). In line with this observation,
[Rh(OTFA)2]2 revealed a high onset potential of Eonset = 1.3 V
vs. Ag/AgCl, which further rationalized as to why [Rh-
(OTFA)2]2 was not catalytically competent (Figure 2b, red).
Likewise, the catalystꢀs mode of action was investigated by
means of DFT studies at the B3LYP-D4/6-311 ++ G**,Rh/
SDD + SMD(DCE)//B3LYP-D3/6-31G**,Rh/SDD level of
theory.[13] Thus, several bimetallic rhodium complexes were
probed, namely monocationic (Figure S9) or dicationic (Fig-
ure 3) RhIII-RhIII as well as monocationic RhII-RhIII (Fig-
Figure 4. Proposed catalytic cycle.
À
Thereafter, the high-valent bimetallic rhodium-induced C
H activation takes place, while, reductive elimination and
decoordination deliver the trifluoroacetate ester 16. Finally,
anodic oxidation regenerates the catalyst 10, with an alter-
native two-electron oxidation pathway being depicted in
Scheme S12.[13]
Conclusion
In conclusion, we have reported on mechanistically-
Figure 3. Computed relative Gibbs free energies (DG298.15) in kcalmolÀ1
À
distinct rhoda-electrocatalysis for C H oxygenations of
À
for the C H activation elementary step at the B3LYP-D4/6-
synthetically useful amides and ketones by challenging weak
O-coordination. In an undivided cell, an easily accessible
ionic liquid and mild reaction conditions set the stage for
311+ +G**,Rh/SDD+SMD(DCE)//B3LYP-D3BJ/6-31G**,Rh/SDD lev-
el of theory for a dicationic RhIII-RhIII complex. In the computed
transition state structure, non-relevant hydrogens were omitted for
clarity.
À
a operationally-friendly C H oxygenation in the absence of
redox mediators. By adjusting the current, valuable dihy-
À
drooxazinones could be selectively assembled by double C H
À
ure S11). According to our findings, a C H rhodation via
functionalization. The application to the late-stage assembly
of Promysalin analogue fragments with a low catalyst loading,
as well as gram-scale bimetallic electrocatalysis accounts for
the considerable practical potential. Detailed mechanistic
dicationic RhIII-RhIII complex was identified as the most
plausible pathway with an activation barrier of 25.1 kcal
molÀ1.
À
On the basis of our mechanistic studies, we propose
a plausible catalytic cycle to be initiated by facile electro-
chemical oxidation of [Rh(OAc)2]2 to generate the rhodium-
(III)-rhodium(II) species 10 (Figure 4). A subsequent anodic
oxidation generates the catalytically competent bimetallic
rhodium(III) species 11. Notably, the bimetallic nature of the
electrocatalysis allows for effective direct oxidations in the
absence of a redox mediator. Then, isomerization and
substrate coordination occur to deliver intermediate 12.
studies revealed an oxidation-induced C H activation by
a bimetallic rhodium catalysis manifold.
Acknowledgements
Generous support by the DFG (Gottfried-Wilhelm-Leibniz
award to L.A.) and the CSC (fellowship to XYH) is gratefully
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1850 – 1857; j) Y.-H. Sun, T.-Y. Sun, Y.-D. Wu, X. Zhang, Y. Rao,
acknowledged. Open access funding enabled and organized
by Projekt DEAL.
Chem. Sci. 2016, 7, 2229 – 2238; k) H. Batchu, S. Bhattacharyya,
R. Kant, S. Batra, J. Org. Chem. 2015, 80, 7360 – 7374; l) K. Kim,
H. Choe, Y. Jeong, J. H. Lee, S. Hong, Org. Lett. 2015, 17, 2550 –
2553; m) G. Li, L. Wan, G. Zhang, D. Leow, J. Spangler, J.-Q. Yu,
J. Am. Chem. Soc. 2015, 137, 4391 – 4397; n) Y.-F. Liang, X.
Wang, Y. Yuan, Y. Liang, X. Li, N. Jiao, ACS Catal. 2015, 5,
6148 – 6152; o) G. Shan, X. Han, Y. Lin, S. Yu, Y. Rao, Org.
Biomol. Chem. 2013, 11, 2318 – 2322; p) P. Y. Choy, F. Y. Kwong,
Org. Lett. 2013, 15, 270 – 273; q) H.-Y. Zhang, H.-M. Yi, G.-W.
Wang, B. Yang, S.-D. Yang, Org. Lett. 2013, 15, 6186 – 6189.
[8] a) K. Yamamoto, M. Kuriyama, O. Onomura, Acc. Chem. Res.
2020, 53, 105 – 120; b) F. Wang, S. S. Stahl, Acc. Chem. Res. 2020,
53, 561 – 574; c) J. C. Siu, N. Fu, S. Lin, Acc. Chem. Res. 2020, 53,
547 – 560; d) J. L. Rçckl, D. Pollok, R. Franke, S. R. Waldvogel,
Acc. Chem. Res. 2020, 53, 45 – 61; e) Q. Jing, K. D. Moeller, Acc.
Chem. Res. 2020, 53, 135 – 143; f) K.-J. Jiao, Y.-K. Xing, Q.-L.
Yang, H. Qiu, T.-S. Mei, Acc. Chem. Res. 2020, 53, 300 – 310;
g) L. Geske, E. Sato, T. Opatz, Synthesis 2020, 52, 2781 – 2794;
h) T. Fuchigami, S. Inagi, Acc. Chem. Res. 2020, 53, 322 – 334;
i) Y. Yuan, A. Lei, Acc. Chem. Res. 2019, 52, 3309 – 3324; j) P.
Xiong, H.-C. Xu, Acc. Chem. Res. 2019, 52, 3339 – 3350; k) M.
Elsherbini, T. Wirth, Acc. Chem. Res. 2019, 52, 3287 – 3296;
l) S. R. Waldvogel, S. Lips, M. Selt, B. Riehl, C. J. Kampf, Chem.
Rev. 2018, 118, 6706 – 6765; m) M. Yan, Y. Kawamata, P. S.
Baran, Chem. Rev. 2017, 117, 13230 – 13319; n) R. Feng, J. A.
Smith, K. D. Moeller, Acc. Chem. Res. 2017, 50, 2346 – 2352;
o) R. Francke, R. D. Little, Chem. Soc. Rev. 2014, 43, 2492 –
2521; p) A. Jutand, Chem. Rev. 2008, 108, 2300 – 2347.
Conflict of interest
The authors declare no conflict of interest.
À
Keywords: cascade · C H activation · electrochemistry ·
oxygenation · rhodium
´
[1] a) Ł. Wozniak, J.-F. Tan, Q.-H. Nguyen, A. Madron du Vignꢁ, V.
Smal, Y.-X. Cao, N. Cramer, Chem. Rev. 2020, 120, 10516 –
10543; b) S. Rej, Y. Ano, N. Chatani, Chem. Rev. 2020, 120,
1788 – 1887; c) P. Gandeepan, T. Mꢂller, D. Zell, G. Cera, S.
Warratz, L. Ackermann, Chem. Rev. 2019, 119, 2192 – 2452; d) Y.
Park, Y. Kim, S. Chang, Chem. Rev. 2017, 117, 9247 – 9301; e) J.
He, M. Wasa, K. S. L. Chan, Q. Shao, J.-Q. Yu, Chem. Rev. 2017,
117, 8754 – 8786; f) O. Daugulis, J. Roane, L. D. Tran, Acc. Chem.
Res. 2015, 48, 1053 – 1064; g) J. Wencel-Delord, F. Glorius, Nat.
Chem. 2013, 5, 369 – 375; h) B. Li, P. H. Dixneuf, Chem. Soc. Rev.
2013, 42, 5744 – 5767; i) D. A. Colby, A. S. Tsai, R. G. Bergman,
J. A. Ellman, Acc. Chem. Res. 2012, 45, 814 – 825; j) L. McMur-
ray, F. OꢀHara, M. J. Gaunt, Chem. Soc. Rev. 2011, 40, 1885 –
1898; k) L. Ackermann, R. Vicente, A. R. Kapdi, Angew. Chem.
Int. Ed. 2009, 48, 9792 – 9826; Angew. Chem. 2009, 121, 9976 –
10011.
[2] a) D. Yasemin, O. Yasemin, O. Orhan, E. Volkan, O. Tijen, M.
Adnan, E. Kevser, M. F. Sahin, Med. Chem. 2012, 8, 481 – 490;
b) G. G. Duthie, A. D. Wood, Food Funct. 2011, 2, 515 – 520;
[9] a) P. Gandeepan, L. H. Finger, T. H. Meyer, L. Ackermann,
Chem. Soc. Rev. 2020, 49, 4254 – 4272; b) T. H. Meyer, I. Choi, C.
Tian, L. Ackermann, Chem 2020, 6, 2484 – 2496; c) H. Wang, X.
Gao, Z. Lv, T. Abdelilah, A. Lei, Chem. Rev. 2019, 119, 6769 –
6787; d) T. H. Meyer, L. H. Finger, P. Gandeepan, L. Acker-
mann, Trends Chem. 2019, 1, 63 – 76; e) Q.-L. Yang, P. Fang, T.-S.
Mei, Chin. J. Chem. 2018, 36, 338 – 352; f) C. Ma, P. Fang, T.-S.
Mei, ACS Catal. 2018, 8, 7179 – 7189; g) N. Sauermann, T. H.
Meyer, Y. Qiu, L. Ackermann, ACS Catal. 2018, 8, 7086 – 7103.
[10] a) L. Massignan, X. Tan, T. H. Meyer, R. Kuniyil, A. M.
Messinis, L. Ackermann, Angew. Chem. Int. Ed. 2020, 59,
3184 – 3189; Angew. Chem. 2020, 132, 3210 – 3215; b) S.-K.
Zhang, J. Struwe, L. Hu, L. Ackermann, Angew. Chem. Int.
Ed. 2020, 59, 3178 – 3183; Angew. Chem. 2020, 132, 3204 – 3209;
c) T. H. Meyer, J. C. A. Oliveira, D. Ghorai, L. Ackermann,
Angew. Chem. Int. Ed. 2020, 59, 10955 – 10960; Angew. Chem.
2020, 132, 11048 – 11053; d) C. Tian, U. Dhawa, J. Struwe, L.
Ackermann, Chin. J. Chem. 2019, 37, 552 – 556; e) A. Shrestha,
M. Lee, A. L. Dunn, M. S. Sanford, Org. Lett. 2018, 20, 204 – 207;
f) Q.-L. Yang, Y.-Q. Li, C. Ma, P. Fang, X.-J. Zhang, T.-S. Mei, J.
Am. Chem. Soc. 2017, 139, 3293 – 3298; g) Y.-Q. Li, Q.-L. Yang,
P. Fang, T.-S. Mei, D. Zhang, Org. Lett. 2017, 19, 2905 – 2908;
h) N. Sauermann, T. H. Meyer, C. Tian, L. Ackermann, J. Am.
Chem. Soc. 2017, 139, 18452 – 18455.
˙
˘
c) D. Ekinci, M. S¸entꢂrk, ꢃ. I. Kꢂfrevioglu, Expert Opin. Ther.
Pat. 2011, 21, 1831 – 1841; d) Z. Rappoport, The chemistry of
phenols, Wiley, Hoboken, 2004.
[3] a) S. De Sarkar, W. Liu, S. I. Kozhushkov, L. Ackermann, Adv.
Synth. Catal. 2014, 356, 1461 – 1479; b) K. M. Engle, T.-S. Mei,
M. Wasa, J.-Q. Yu, Acc. Chem. Res. 2012, 45, 788 – 802.
[4] F. Mo, L. J. Trzepkowski, G. Dong, Angew. Chem. Int. Ed. 2012,
51, 13075 – 13079; Angew. Chem. 2012, 124, 13252 – 13256.
[5] G. Shan, X. Yang, L. Ma, Y. Rao, Angew. Chem. Int. Ed. 2012, 51,
13070 – 13074; Angew. Chem. 2012, 124, 13247 – 13251.
´
[6] a) Q. Bu, R. Kuniyil, Z. Shen, E. Gonka, L. Ackermann, Chem.
Eur. J. 2020, 26, 16450 – 16454; b) G. G. Dias, T. Rogge, R.
Kuniyil, C. Jacob, R. F. S. Menna-Barreto, E. N. da Silva Jfflnior,
L. Ackermann, Chem. Commun. 2018, 54, 12840 – 12843; c) K.
Raghuvanshi, D. Zell, L. Ackermann, Org. Lett. 2017, 19, 1278 –
1281; d) F. Yang, K. Rauch, K. Kettelhoit, L. Ackermann,
Angew. Chem. Int. Ed. 2014, 53, 11285 – 11288; Angew. Chem.
2014, 126, 11467 – 11470; e) F. Yang, L. Ackermann, Org. Lett.
2013, 15, 718 – 720; f) W. Liu, L. Ackermann, Org. Lett. 2013, 15,
3484 – 3486; g) V. S. Thirunavukkarasu, J. Hubrich, L. Acker-
mann, Org. Lett. 2012, 14, 4210 – 4213; h) V. S. Thirunavukkar-
asu, L. Ackermann, Org. Lett. 2012, 14, 6206 – 6209.
[11] a) L. Ackermann, Acc. Chem. Res. 2020, 53, 84 – 104; b) Y. Qiu,
J. Struwe, L. Ackermann, Synlett 2019, 30, 1164 – 1173.
[7] a) Q. Gou, X. Tan, M. Zhang, M. Ran, T. Yuan, S. He, L. Zhou,
T. Cao, F. Luo, Org. Lett. 2020, 22, 1966 – 1971; b) M. Baktha-
doss, P. Vijay Kumar, R. Kumar, V. Agarwal, Org. Biomol.
Chem. 2019, 17, 4465 – 4469; c) Z.-l. Li, K.-k. Sun, C. Cai, Org.
Chem. Front. 2019, 6, 637 – 642; d) Y.-C. Yuan, C. Bruneau, V.
Dorcet, T. Roisnel, R. Gramage-Doria, J. Org. Chem. 2019, 84,
1898 – 1907; e) Y.-C. Yuan, C. Bruneau, T. Roisnel, R. Gramage-
Doria, Org. Biomol. Chem. 2019, 17, 7517 – 7525; f) C. Chen, Y.
Pan, H. Zhao, X. Xu, J. Xu, Z. Zhang, S. Xi, L. Xu, H. Li, Org.
Chem. Front. 2018, 5, 415 – 422; g) A. Mishra, T. K. Vats, M. P.
Nair, A. Das, I. Deb, J. Org. Chem. 2017, 82, 12406 – 12415; h) Y.
Wu, B. Zhou, Org. Lett. 2017, 19, 3532 – 3535; i) T. H. L. Nguyen,
N. Gigant, S. Delarue-Cochin, D. Joseph, J. Org. Chem. 2016, 81,
[12] a) A. Modak, U. Dutta, R. Kancherla, S. Maity, M. Bhadra, S. M.
Mobin, D. Maiti, Org. Lett. 2014, 16, 2602 – 2605; b) R. Mueller,
S. Rachwal, M. E. Tedder, Y.-X. Li, S. Zhong, A. Hampson, J.
Ulas, M. Varney, L. Nielsson, G. Rogers, Bioorg. Med. Chem.
Lett. 2011, 21, 3927 – 3930; c) G. R. Madhavan, R. Chakrabarti,
K. Anantha Reddy, B. M. Rajesh, V. Balraju, P. Bheema Rao, R.
Rajagopalan, J. Iqbal, Bioorg. Med. Chem. 2006, 14, 584 – 591.
[13] For detailed information, see the Supporting Information.
[14] L. E. Shmukler, M. S. Gruzdev, N. O. Kudryakova, Y. A. Fadee-
va, A. M. Kolker, L. P. Safonova, RSC Adv. 2016, 6, 109664 –
109671.
Angew. Chem. Int. Ed. 2021, 60, 2 – 9
ꢀ 2021 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH
www.angewandte.org
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These are not the final page numbers!

Angewandte
Research Articles
Chemie
[15] a) C. E. Keohane, A. D. Steele, C. Fetzer, J. Khowsathit, D.
Van Tyne, L. Moyniꢁ, M. S. Gilmore, J. Karanicolas, S. A. Sieber,
W. M. Wuest, J. Am. Chem. Soc. 2018, 140, 1774 – 1782; b) A. D.
Steele, C. E. Keohane, K. W. Knouse, S. E. Rossiter, S. J.
Williams, W. M. Wuest, J. Am. Chem. Soc. 2016, 138, 5833 –
5836; c) A. D. Steele, K. W. Knouse, C. E. Keohane, W. M.
Wuest, J. Am. Chem. Soc. 2015, 137, 7314 – 7317; d) W. Li, P.
Estrada-de los Santos, S. Matthijs, G.-L. Xie, R. Busson, P.
Cornelis, J. Rozenski, R. De Mot, Chem. Biol. 2011, 18, 1320 –
1330.
Manuscript received: December 31, 2020
Revised manuscript received: February 28, 2021
Accepted manuscript online: March 2, 2021
Version of record online: && &&
,
&&&&
&&&&
www.angewandte.org
ꢀ 2021 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH
Angew. Chem. Int. Ed. 2021, 60, 2 – 9
These are not the final page numbers!

Angewandte
Research Articles
Chemie
Research Articles
À
À
C H Activation
Rhodium-electrocatalyzed C H oxygen-
ations of amides and ketones proved
viable under mild conditions via bimet-
allic electrocatalysis. Mechanistic studies
revealed a high-valent dimeric rhodium
electrocatalysis.
X. Tan, L. Massignan, X. Hou, J. Frey,
J. C. A. Oliveira, M. N. Hussain,
L. Ackermann*
&&&& — &&&&
À
Rhoda-Electrocatalyzed Bimetallic C H
Oxygenation by Weak O-Coordination
Angew. Chem. Int. Ed. 2021, 60, 2 – 9
ꢀ 2021 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH
www.angewandte.org
&&&&
These are not the final page numbers!