Electrocatalytic Deuteration of Halides with D2O as the Deuterium Source over a Copper Nanowire Arrays Cathode

Article abstract of DOI:10.1002/anie.202009155

Precise deuterium incorporation with controllable deuterated sites is extremely desirable. Here, a facile and efficient electrocatalytic deuterodehalogenation of halides using D₂O as the deuteration reagent and copper nanowire arrays (Cu NWAs) electrochemically formed in situ as the cathode was demonstrated. A cross-coupling of carbon and deuterium free radicals might be involved for this ipso-selective deuteration. This method exhibited excellent chemoselectivity and high compatibility with the easily reducible functional groups (C=C, C≡C, C=O, C=N, C≡N). The C?H to C?D transformations were achieved with high yields and deuterium ratios through a one-pot halogenation–deuterodehalogenation process. Efficient deuteration of less-active bromide substrates, specific deuterium incorporation into top-selling pharmaceuticals, and oxidant-free paired anodic synthesis of high-value chemicals with low energy input highlighted the potential practicality.

Full text of DOI:10.1002/anie.202009155

A Journal of the Gesellschaft Deutscher Chemiker
Angewandte
Chemie
International Edition
www.angewandte.org
Accepted Article
Title: Electrocatalytic Deuteration of Halides with D2O as the
Deuterium Source over a Copper Nanowire Arrays Cathode
Authors: Cuibo Liu, Shuyan Han, Mengyang Li, Xiaodan Chong, and
Bin Zhang
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.202009155
Link to VoR: https://doi.org/10.1002/anie.202009155

10.1002/anie.202009155
Angewandte Chemie International Edition
COMMUNICATION
Electrocatalytic Deuteration of Halides with D2O as the Deuterium
Source over a Copper Nanowire Arrays Cathode
Cuibo Liu,+,[a] Shuyan Han,+,[a] Mengyang Li,[a] Xiaodan Chong,[a] and Bin Zhang*,[a],[b]
[a]
C. Liu, S. Han, M. Li, X. Chong, Prof. B. Zhang
Institute of Molecular Plus, Department of Chemistry, School of Science
Tianjin University
Tianjin 300072, China
E-mail: bzhang@tju.edu.cn
[b]
[+]
Prof. B. Zhang
Tianjin Key Laboratory of Molecular Optoelectronic Sciences, Frontiers Science Center for Synthetic Biology (Ministry of Education)
Tianjin University
Tianjin 300072, China
These authors contributed equally to this work.
Supporting information for this article is given via a link at the end of the document.
Abstract: Precise deuterium incorporation with controllable
deuterated sites and amount is extremely desirable. Here, a facile
and efficient electrocatalytic deuterodehalogenation of halides using
heavy water (D2O) as the deuteration reagent and electrochemical in
situ formed copper nanowire arrays (Cu NWAs) as the cathode was
demonstrated. A cross-coupling of carbon and deuterium free
radicals might be involved for this ipso-selective deuteration. This
method exhibited excellent chemoselectivity and high compatibility
with the easily reducible functional groups such as C=C, C≡C, C=O,
C=N, and C≡N bonds. The C–H to C–D transformations were
successfully achieved with high yields and deuterium ratios through
a one-pot halogenation-deuterodehalogenation process. Efficient
deuteration of less-active bromide substrates, specific deuterium
incorporation into top-selling pharmaceuticals, and oxidant-free
paired anodic synthesis of high-value chemicals with low energy
input highlighted the potential practicality.
deuterated sites and amounts, and excellent deuterium purity is
highly desirable.
Recently, the electrochemical transformation has emerged as
a powerful and green tool in synthetic chemistry.[32-36] The high
tunability by the applied potential or current makes it very
suitable for various redox reactions.[37-44] Among the
transformations, the electrochemical reduction reactions are
regarded as the most promising, including electrocatalytic water
splitting, carbon dioxide reduction reaction, or nitrogen reduction
reaction.[45-47] During these transformations, the highly active
hydrogen (*H) species is well-accepted as the key intermediate
that generates and adsorbs on the surface of the cathode via
water splitting.[45-48] Thus, it is reasonable and extremely urgent
to develop electrochemical organic reduction reactions using the
in situ formed *H as a strong reducing agent, which is far from
being fully developed.[49-52] Despite the important advance was
achieved in the electrocatalytic dehalogenative deuteration of
aryl halides,[28] a large amount of expensive CD3CN, the high-
cost electrolyte, and the organic additive were required in the
pure organic solvent with a few substrate cases and the unclear
mechanism.
Deuterium labeling plays a crucial role in synthetic chemistry,
materials science, and pharmaceutical industry due to the kinetic
isotope effect.[1-5] Since the first deuterated drug of Austedo has
been approved, the research interest has been boosted rapidly
to the synthesis of deuterated pharmaceuticals (Figure 1a).[6-11]
However, precise deuteration with controllable numbers and
locations still remains a great challenge. The C–H/C–D ex-
change is a straightforward strategy for deuterium incorporation
without pre-functionalization.[12] However, noble-metal catalysts
and strong bases/acids are often required to activate the robust
C–H bonds. The deuterated sites and numbers are unruly; and
the deuterated ratios are usually low.[13-17] In contrast, the
deuterodehalogenation of halides provides an alternative to
diversified deuterated molecules owing to the easier activation of
C–X (X is a halogen) bonds and the ipso-selective deuteration
manner.[18-19] Despite effectiveness, the typical metal-halogen
exchange or transition-metal-catalyzed processes always use
noble metal catalysts with complex ligands, special deuterium
donors, and highly active alkyl-metal reagents under anaerobic
Figure 1. (a) Selected deuterated drugs. (b) Proposed electrocatalytic precise
deuteration of halides with D2O over a Cu NWAs cathode.
and
cryogenic
conditions,
retarding
their
practical
Here, by employing noble-metal-free Cu copper nanowire
arrays (Cu NWAs) as the cheap cathode, an electrocatalytic
reductive deuteration of halides with wide substrate scopes and
good functional group tolerance was reported using low-cost and
safe D2O as the deuterium source under ambient conditions
(Figure 1b). One-pot halogenation-deuterodehalogenation of C–
H to C–D bonds, efficient deuteration of less-active bromides
including the salable pharmaceuticals, and simultaneous
applications.[20-24] Whereas, radical reductive deuteration of
halides usually suffers from the photocorrosion-induced
instability of photocatalysts, concurrent side reactions of
sacrificial agents, and low deuterated efficiency for less
activated bromides due to the narrow redox-potential window.[25-
31] Therefore, developing a general and mild method for efficient
deuterium incorporation with broad substrate scopes, precise
This article is protected by copyright. All rights reserved.

10.1002/anie.202009155
Angewandte Chemie International Edition
COMMUNICATION
oxidative preparation of synthetically useful feedstock at anode
without additional oxidants could be fulfilled by using this
electrocatalytic strategy.
disappearance of satellite Cu 2p peaks at 916.6 eV and 943.1
eV, respectively, and no observation of O 1s signal further
confirmed the phase transformation.[55] All these results
indicated the successful preparation of Cu NWAs.
Figure 2. a) Scheme illustrating electrochemical in situ synthesis of self-
supported Cu NWAs. b) SEM images of as-prepared Cu NWAs. c) In situ
Raman spectra collected at -1.1 V vs. Hg/HgO (similarly hereinafter) in 0.5 M
K2CO3 solution (AN/H2O, 1:1 v/v, 6.0 mL). d) XRD patterns and e) XPS
spectra of CuO and Cu NWAs.
Figure 3. a) LSV curves of Cu NWAs at a scan rate of 10 mV s-1 in 0.5 M
K2CO3 solution (AN/D2O, 1:1 v/v) with and without 0.5 mmol of 1a. b)
Potential-dependent conversions of 1a over Cu NWAs. c) Comparison results
of converting 1a to 2a over different cathode materials (-1.1 V vs. Hg/HgO). d)
Cycle-dependent performance of converting 1a to 2a over Cu NWAs (-1.1 V vs.
Hg/HgO). e)
A
proposed possible mechanism for electrochemical
For an electrochemical reduction in water, developing a suit-
able cathode to balance the competing hydrogen evolution is a
key to obtain high efficiency. Cu cathode is proved to have weak
adsorption for *H, which is favorable to engage in the reduction
reactions.[45,53] To enhance the performance, self-supported Cu
NWAs on Cu foil were in situ fabricated by electrochemical
reduction of CuO NWAs (Figure 2a, see the Supporting
Information for details). Scanning electron microscopy (SEM)
images revealed that the morphology of Cu nanowires
maintained well after the electrochemical reduction (Figure 2b).
Such self-supported nanostructures with large surface areas can
provide abundant active sites and accelerate electron/mass
transfer. A thorough disappearance of the cathodic peak from
the cycle-dependent cyclic voltammograms (CV) revealed the
successful conversion of CuO to Cu (Figure S2). In situ Raman
spectra showed that the characteristic peaks of CuO at around
274.8 cm−1 disappeared, and the characteristic peaks of Cu2O
(150 and 221.38 cm−1) first grew and then vanished, suggesting
the electroreduction induced conversion of CuO to Cu2O and
subsequent Cu2O to Cu (Figure 2c).[54] All the diffraction peaks in
the X-ray diffraction (XRD) pattern can be indexed to Cu
(JCPDS NO. 65-9743) (Figure 2d). In the X-ray photoelectron
spectroscopy (XPS) data (Figures 2e and S1c), the
deuterodehalogenation of halides. f) EPR trapping for hydrogen (*) and carbon
(#) radicals. Con. = conversion, sel. = selectivity. The con. and sel. are
determined by gas chromatography (GC).
The electrocatalytic deuteration of halides over in situ
generated Cu NWAs was carried out in a divided three-electrode
system in a 0.5 M K2CO3 solution with anhydrous acetonitrile
(AN) and D2O (1:1 v/v, 6.0 mL) as the co-solvent (Figure S3).
After Cu NWAs were in situ formed, 0.5 mmol of halides were
added into the electrolytic cell for the following
deuterodehalogenation. The linear sweep voltammetry (LSV)
curves (Figure 3a) displayed an obvious increase in current
density after the addition of 4-Iodoaniline (1a), indicating the
electrochemical reduction of 1a over Cu NWAs cathode. As
shown in potential-dependent results (Figure 3b), nearly no
deuterated product 2a was observed at -0.7 V, which might be
associated with the more negative reduction potential of 1a than
the applied potential. 2a could be obtained with up to 99%
conversion yield, 99% deuterium incorporation, and 79.2%
Faradaic efficiency at -1.1 V without H/D exchange in an amino
N–H group. Further lowering the potential resulted in decreased
yields of 2a. This might be attributed to the interference of the
This article is protected by copyright. All rights reserved.

10.1002/anie.202009155
Angewandte Chemie International Edition
COMMUNICATION
Table 1. Electrochemical deuterodehalogenation of halides using D2O over a
Cu NWAs cathode.
without electricity showed the electrochemical-mediated process
(Scheme S1). Interestingly, the selective deuteration of 1a could
be driven by a 1.5 V battery with comparable yield and
deuterated ratio, revealing the remarkable flexibility of our
strategy (Figure S6).
A radical pathway for the possible mechanism was proposed
for the electrocatalytic deuteration of the C–X bond by D2O
(Figure 3e). Electron transfer from Cu cathode surface to halides
generating the carbon radicals via either stepwise process or
concerted pathway by releasing a halogen anion (inset of Figure
3e). Then, the carbon radicals coupled with the deuterium
radicals produced via electrocatalytic D2O splitting to form the
desired products. Both the carbon and hydrogen radicals were
confirmed by the electron paramagnetic resonance (EPR)
measurements using 5,5-dimethyl-1-pyrroline-N-oxide (DMPO)
as the trapping agent (Figure 3f).[29,56,57] A decreased conversion
of the product after adding tertiary butanol (t-BuOH), which could
scavenge the hydrogen atoms, was observed, identifying the
role of hydrogen radicals in this electrocatalytic reduction
reaction (Figure S7). However, a direct abstraction of deuterium
atom from the D2O molecule by carbon radicals for deuterium
incorporation could not be fully ruled out.[58-60]
Then, we investigated the substrate scopes. The reactivity of
iodinated halides was first examined. A series of functionalized
aryl iodides could be transformed into the corresponding
deuterated products with good conversion yields and deuterated
ratios no matter where the functional groups lay on the aryl ring
(Table 1, 2a-2j). Of note, the electrochemical deuteration
occurred solely at C–I moiety in the presence of the C–Cl bond,
showing the high selectivity. Additionally, the aliphatic primary
iodide could work smoothly, delivering 2j in 92% yield.
aReaction conditions: halides substrates (0.3 mmol), Cu NWAs (working area:
1 cm2), 0.5 M K2CO3 (AN/D2O, 1:1 v/v, 6 mL), room temperature, -1.1 V.
Conversion yields (con.) were reported. bIsolated yields. c0.1 mmol of 3 was
used as the starting materials.
electron transfer process caused by competitive hydrogen gas
(H2) bubbles on the electrode surface. Time-dependent
transformation revealed that the reaction could be finished within
2 h at -1.1 V (Figure S5). Using Pt, nickel foam, and carbon
paper as the cathodes, inferior efficiencies were observed,
demonstrating the specialty and necessity of Cu in this
electrochemical deuteration reaction (Figure 3c). A lower yield of
2a by employing pure Cu foil as the cathode indicated the
promoted effect of nanowire array structures in this reaction. Up
to 93% yield of 2a was still obtained for the fifth cycle (Figure 3d),
and no obvious changes in the recycled Cu NWAs were
observed by SEM, XPS, and XRD (Figures S4a-d), suggesting
the good stability. Only hydrogenated product was delivered
when employing CD3CN/H2O as the solvent, proving water was
the sole hydrogen source (Scheme S1). No product formed
Figure 4. Coupling of cathodic dehalogenative deuteration with oxidant-free
synthesis of value-added chemicals at anode in a Cu NWAs || Ni2P NSs two-
electrode electrolyzer.
Our strategy was well applied to the deuteration of less-
active bromides (Table 1, 2k-4d), which usually give low
efficiency by current radical reductive methods.[25-29] Due to the
mild reaction conditions and the catalytic specificity of Cu NWAs
cathodes, other reducible functional groups commonly present in
pharmaceuticals (e.g. C≡N, C≡C, C=C, C=O, and C=N) could be
retained well, providing rich opportunities for downstream
fabrication of complex deuterated molecules (Table 1, 2k-2o). In
addition, the drug-related molecules containing pyridine,
quinolone, indole, and pyrimidine skeletons were well deuterated
with 80-93% deuterium ipso-selectivity (Table 1, 2p-2s).
This article is protected by copyright. All rights reserved.

10.1002/anie.202009155
Angewandte Chemie International Edition
COMMUNICATION
[2]
Y. Dai, P. Ren, Y. Li, D. Lv, Y. Shen, Y. Li, H. Niemantsvedrit, F.
Besenbacher, H. Xiang, W. Hao, N, Lock , X. Wen, J. P. Lewis, R. Su,
Angew. Chem. Int. Ed. 2019, 58, 6265-6270; Angew. Chem. 2019, 131,
6331-6336.
Impressively, one-pot halogenation-deuterodehalogenation of
original C–H bonds to C–D bonds was feasibly realized with
good yields and deuterium contents, allowing us to produce
deuterated aromatics bypassing the tedious purification of halide
precursors (Table 1, 2t-2w). The deuterium incorporation could
alter the drug’s metabolism and pharmacokinetic properties.[6-11]
Our method can be applied to the deuteration of top-selling
pharmaceuticals via the halogenation-deuterodehalogenation of
original drug molecules (Table 1, 4a-4d). For example, Nicotinic
acid is among the top 200 prescribed drugs by retail sales in
2009.[61] Site-specific deuteration may provide a platform to
enhance the therapeutic benefit, reduce the drug dose, lower the
side effect, etc.
Finally, electrooxidation reactions of organic compounds
were implemented at the anode to replace low-value oxygen
evolution adopted a Cu NWAs || Ni2P nanosheets (NSs) two-
electrode electrolyzer (Figure 4, see the Supporting Information
for details).[62-66] Interestingly, 2a could also be synthesized with
up tp 99% yield at the Cu NWAs cathode, while benzonitrile (6a)
and benzaldehyde (6b) were separately generated at the N2P
NSs anode with excellent conversion yields and selectivity (Sel.),
highlighting the potential practicability.
[3]
[4]
T. D. Nguyen, G. Hukic-Markosian, F. Wang, L. Wojcik, X. G. Li, E.
Ehrenfreund, Z. V. Vardeny, Nat. Mater. 2010, 9, 345−352.
J. Atzrodt, V. Derdau, W. J. Kerr, M. Reid, Angew. Chem. Int. Ed. 2018,
57, 1758−1784; Angew. Chem. 2018, 130, 1774−1802.
T. G. Gant, J. Med. Chem. 2014, 57, 3595−3611.
[5]
[6]
[7]
C. Schmidt, Nat. Biotechnol. 2017, 35, 493−494.
Y. Y. Loh, K. Nagao, A. J. Hoover, D. Hesk, N. R. Rivera, S. L. Colletti,
I. W. Davies, D. W. C. MacMillan, Science 2017, 358, 1182−1187.
Y. Chang, A. Yesilcimen, M. Cao, Y. Zhang, B. Zhang, J. Z. Chan, M.
Wasa, J. Am. Chem. Soc. 2019, 141, 14570−14575.
[8]
[9]
C. Zarate, H. Yang, M. J. Bezdek, D. Hesk, P. J. Chirik, J. Am. Chem.
Soc. 2019, 141, 5034−5044.
[10] J. L. Koniarczyk, D. Hesk, A. Overgard, I. W. Davies, A. McNally, J. Am.
Chem. Soc. 2018, 140, 1990−1993.
[11] R. P. Yu, D. Hesk, N. Rivera, I. Pelczer, P. J. Chirik, Nature 2016, 529,
195−199.
[12] J. Atzrodt, V. Derdau, W. J. Kerr, M. Reid, Angew. Chem. Int. Ed. 2018,
57, 3022−3047; Angew. Chem. 2018, 130, 3074−3101.
[13] W. J. Kerr, M. Reid, T. Tuttle, Angew. Chem. Int. Ed. 2017, 56,
7808−7812; Angew. Chem. 2017, 129, 7916−7920.
[14] H. Xu, M. Liu, L. J. Li, Y. F. Cao, J. Q. Yu, H. X. Dai, Org. Lett. 2019, 21,
4887−4891.
In conclusion, an electrocatalytic deuteration of halides over
an in situ formed Cu NWAs cathode was demonstrated to
synthesize a wide range of deuterated compounds with high
yields and moderate to high deuterium purity by using cheap,
safe, and easy-to-handling D2O as the deuterated source. Cu
NWAs cathodes with robust and recyclable properties could
[15] M. H. G. Prechtl, M. Hölscher, Y. Ben-David, N. Theyssen, R. Loschen,
D. Milstein, W. Leitner, Angew. Chem. Int. Ed. 2007, 46, 2269−2272;
Angew. Chem. 2007, 119, 2319 –2322.
[16] M. H. Emmert, J. B. Gary, J. M. Villalobos, M. S. Sanford, Angew.
Chem. Int. Ed. 2010, 49, 5884−5886; Angew. Chem. 2010, 122, 6020–
6022.
efficiently
engage
in
one-pot
halogenation-
[17] L. V. A. Hale, N. K. Szymczak, J. Am. Chem. Soc. 2016, 138,
13489−13492.
deuterodehalogenation of C–H to C–D bonds without isolating
the halide precursors, showing good step economy. The easily
fragile moieties commonly present in pharmaceuticals (e.g. C≡N,
C≡C, C=C, C=O, and C=N) survived well, and less-active
bromides could be effectively deuterated. A cross-coupling
between the carbon and deuterium free radicals might be
involved in this method. Additionally, our strategy could be
successfully applied to the deuteration of top-selling
pharmaceuticals to possibly alter their therapeutic profiles.
Moreover, paired fabrication of synthetically useful feedstock
such as nitrile, aldehyde, and dihydroquinoline at anode under
oxidant-free conditions highlighted the potential utility of our
method.
[18] F. Alonso, I. P. Beletskaya, M. Yus, Chem. Rev. 2002, 102, 4009−4018.
[19] Y. Yuan, A. Yao, Y. Zheng, M. Gao, Z. Zhou, J. Qiao, J. Hu, B. Ye, J.
Zhao, H. Wen, A. Lei, iScience 2019, 12, 293−303.
[20] D. Salinger, R. Brückner, Chem. Eur. J. 2009, 15, 6688−6703.
[21] M. Janni, S. Peruncheralathan, Org. Biomol. Chem. 2016, 14,
3091−3097.
[22] X. Wang, M. H. Zhu, D. P. Schuman, D. Zhong, W. Y. Wang, L. Y. Wu,
W. Liu, B. M. Stoltz, W. B. Liu, J. Am. Chem. Soc. 2018, 140,
10970−10974.
[23] F. Alonso, Y. Moglie, G. Radivoy, C. Vitale, M. Yus, Appl. Catal. A: Gen.
2004, 271, 171–176.
[24] M. Kuriyama, N. Hamaguchi, G. Yano, K. Tsukuda, K. Sato, O.
Onomura, J. Org. Chem. 2016, 81, 8934−8946.
[25] T. Mutsumi, K. Maruhashi, Y. Monguchi, H. Sajiki, Synlett 2008, 18,
2811−2814.
[26] T. Mutsumi, H. Iwata, K. Maruhashi, Y. Monguchi, H. Sajiki, Tetrahedron
2011, 67, 1158−1165.
Acknowledgements
[27] V. Soulard, G. Villa, D. P. Vollmar, P. Renaud, J. Am. Chem. Soc. 2018,
140, 155−158.
We do appreciate the National Natural Science Foundation of
China (No. 21871206 and No. 21422104) for financial support.
[28] K. Mitsudo, T. Okada, S. Shimohara, H. Mandai, S. Suga,
Electrochemistry 2013, 81, 362−364.
[29] Y. Dong, Y. Su, L. Du, R. Wang, L. Zhang, D. Zhao, W. Xie, ACS Nano
2019, 13, 10754−10760.
Conflict of interest
[30] C. Liu, Z. Chen, C. Su, X. Zhao, Q. Gao, G. H. Ning, H. Zhu, W. Tang, K.
Leng, W. Fu, B. Tian, X. Peng, J. Li, Q. H. Xu, W. Zhou, K. P. Loh, Nat.
Commun. 2018, 9, 80.
The authors declare no conflict of interest.
Keywords: electrocatalysis • deuteration • D2O • paired
reaction • in situ formed Cu nanostructures
[31] J. Ke, H. Wang, L. Zhou, C. Mou, J. Zhang, L. Pan, Y. R. Chi, Chem.
Eur. J. 2019, 25, 6911−6914.
[32] Y. Jiang, K. Xu, C. Zeng, Chem. Rev. 2018, 118, 4485−4540.
[33] M. Yan, Y. Kawamata, P. S. Baran, Chem. Rev. 2017, 117,
13230−13319.
[1]
M. Miyashita, M. Sasaki, I. Hattori, M. Sakai, K. Tanino, Science 2004,
305, 495−499.
[34] P. Xiong, H. C. Xu, Acc. Chem. Res. 2019, 52, 3339−3350.
This article is protected by copyright. All rights reserved.

10.1002/anie.202009155
Angewandte Chemie International Edition
COMMUNICATION
[35] R. Francke, R. D. Little, Chem. Soc. Rev. 2014, 43, 2492−2521.
[36] Y. Yuan, A. Lei, Acc. Chem. Res. 2019, 52, 3309−3324.
[37] Q. L. Yang, X. Y. Wang, J. Y. Lu, L. P. Zhang, P. Fang, T. S. Mei, J. Am.
Chem. Soc. 2018, 140, 11487−11494.
[57] D. Wang, P. Wang, S. Wang, Y. H. Chen, H. Zhang, A. Lei, Nat.
Commun. 2019, 10, 2796.
[58] E. T. Martin, C. M. McGuire, M. S. Mubarak, D. G. Peters, Chem. Rev.
2016, 116, 15198 8−15234.
[38] R. Mei, N. Sauermann, J. C. A. Oliveira, L. Ackermann, J. Am. Chem.
Soc. 2018, 140, 7913−7921.
[59] A. A. Isse, A. Gennaro, C. Y. Lin, J. L. Hodgson, M. L. Coote, T.
Guliashvili, J. Am. Chem. Soc. 2011, 133, 6254−6264.
[39] N. Fu, G. S. Sauer, A. Saha, A. Loo, S. Lin, Science 2017, 357,
575−579.
[60] P. Wang, Z. Yang, Z. Wang, C. Xu, L. Huang, S. Wang, H. Zhang, A. Lei,
Angew. Chem. Int. Ed. 2019, 58, 15747−15751; Angew. Chem. 2019,
131, 15894 –15898.
[40] M. Rafiee, M. Alherech, S. D. Karlen, S. S. Stahl, J. Am. Chem. Soc.
2019, 141, 15266−15276
[61] N. A. McGrath, M. Brichacek, J. T. Njardarson, J. Chem. Educ. 2010, 87,
1348−1349.
[41] N. Fu, L. Li, Q. Yang, S. Luo, Org. Lett. 2017, 19, 2122−2125.
[42] P. Zhang, X. Sheng, X. Chen, Z. Fang, J. Jiang, M. Wang, F. Li, L. Fan,
Y. Ren, B. Zhang, B. J. J. Timmer, M. S. G. Ahlquist, L. Sun, Angew.
Chem. Int. Ed. 2019, 58, 9155-9159; Angew. Chem. 2019, 131,
9155−9159.
[62] C. Huang, Y. Huang, C. Liu, Y. Yu, B. Zhang, Angew. Chem. Int. Ed.
2019, 58, 12014−12017; Angew. Chem. 2019, 131, 12142–12145.
[63] S. Barwe, J. Weidner, S. Cychy, D. M. Morales, S. Dieckhofer, D. Hiltrop,
J. Masa, M. Muhler, W. Schuhmann, Angew. Chem. Int. Ed. 2018, 57,
11460-11464; Angew. Chem. 2018, 130, 11631−11636.
[64] W. Li, N. Jiang, B. Hu, X. Liu, F. Song, G. Han, T. J. Jordan, T. B.
Hanson, T. L. Liu, Y. Sun, Chem 2018, 4, 637−649.
[43] X. Chong, C. Liu, Y. Huang, C. Huang, B. Zhang, Natl. Sci. Rev. 2020, 7,
285−295.
[44] Y. Jiang, R. Long, Y. Xiong, Chem. Sci. 2019, 10, 7310−7326.
[45] C. G. Morales-Guio, L. A. Stern, X. Hu, Chem. Soc. Rev. 2014, 43,
6555−6569.
[65] B. You, Y. Sun, Acc. Chem. Res. 2018, 51, 1571−1580.
[66] C. Tang, R. Zhang, W. Lu, Z. Wang, D. Liu, S. Hao, G. Du, A. M. Asiri, X.
Sun, Angew. Chem. Int. Ed. 2017, 56, 842-846; Angew. Chem. 2017,
129, 860−864.
[46] Z. W. Seh, J. Kibsgaard, C. F. Dickens, I. Chorkendorff, J. K. Nørskov, T.
F. Jaramillo, Science 2017, 355, eaad4998.
[47] J. M. Cornelis, V. D. Ham, M. T. M. Koper, D. G. H. Hetterscheid, Chem.
Soc. Rev. 2014, 43, 5183−5191.
[48] Y. Zhao, C. Liu, C. Wang, X. Chong, B. Zhang, CCS Chem. 2020, 2,
507–515.
[49] B. K. Peters, K. X. Rodriguez, S. H. Reisberg, S. B. Beil, D. P. Hickey, Y.
Kawamata, M. Collins, J. Starr, L. Chen, S. Udyavara, K. Klunder, T. J.
Gorey, S. L. Anderson, M. Neurock, S. D. Minteer, P. S. Baran, Science
2019, 363, 838−845.
[50] R. S. Sherbo, A. Kurimoto, C. M. Brown, C. P. Berlinguette, J. Am.
Chem. Soc. 2019, 141, 7815−7821.
[51] B. Li, H. Ge, Sci. Adv. 2019, 5, eaaw2774.
[52] C. J. Bondue, M. T. M. Koper, J. Am. Chem. Soc. 2019, 141,
12071−12078.
[53] S. Roger, M. A. Shipman, M. D. Symes, Nat. Rev. Chem. 2017, 1, 0003.
[54] Y. Wang, W. Zhou, R. Jia, Y. Yu, B. Zhang, Angew. Chem. Int. Ed. 2020,
59, 5350−5354; Angew. Chem. 2020, 132, 5388−5392.
[55] P. Jiang, D. Prendergast, F. Borondics, S, Porsgaard, L. Giovanetti, E.
Pach, J. Newberg, H. Bluhm, F. Besenbacher, M. Salmeron, J. Chem.
Phys. 2013, 138, 024704.
[56] N. A. Bauera, E. Hoquea, M. Wolfa, K. Kleigreweb, T. Hofmannb, Free
Radic. Biol. Med. 2018, 116, 129−133.
This article is protected by copyright. All rights reserved.

10.1002/anie.202009155
Angewandte Chemie International Edition
COMMUNICATION
Entry for the Table of Contents
In situ formed Cu nanowire arrays were efficient catalysts for controllable deuteration of halides using D2O as a cheap and safe
deuterated donor. A cross-coupling of carbon and deuterium free radicals might be involved in this reaction. High compatibility with
easily reducible functional groups, one-pot C–H to C–D transformation, and paired synthesis of valuable chemicals at both electrodes
showed the potential utility.
This article is protected by copyright. All rights reserved.