Merging shuttle reactions and paired electrolysis for reversible vicinal dihalogenations

Article abstract of DOI:10.1126/science.abf2974

Vicinal dibromides and dichlorides are important commodity chemicals and indispensable synthetic intermediates in modern chemistry that are traditionally synthesized using hazardous elemental chlorine and bromine. Meanwhile, the environmental persistence of halogenated pollutants necessitates improved approaches to accelerate their remediation. Here, we introduce an electrochemically assisted shuttle (e-shuttle) paradigm for the facile and scalable interconversion of alkenes and vicinal dihalides, a class of reactions that can be used both to synthesize useful dihalogenated molecules from simple alkenes and to recycle waste material through retro-dihalogenation. The reaction is demonstrated using 1,2-dibromoethane, as well as 1,1,1,2-tetrachloroethane or 1,2-dichloroethane, to dibrominate or dichlorinate, respectively, a wide range of alkenes in a simple setup with inexpensive graphite electrodes. Conversely, the hexachlorinated persistent pollutant lindane could be fully dechlorinated to benzene in soil samples using simple alkene acceptors.

Full text of DOI:10.1126/science.abf2974

RESEARCH
favor halogen transfer over hydrogen trans-
fer is crucial to unlock this important class of
transfer difunctionalization reactions.
ORGANIC CHEMISTRY
Merging shuttle reactions and paired electrolysis for
reversible vicinal dihalogenations
Xichang Dong1*, Johannes L. Roeckl1,2*, Siegfried R. Waldvogel2†, Bill Morandi1†
Electrosynthesis has recently experienced a
renaissance in organic chemistry because it
takes advantage of readily available electrical
current as a sustainable and inherently safe
redox reagent (21–24). Notable advances have
been made in halogenation reactions (25, 26),
as illustrated by an elegant example of di-
chlorination from Lin et al. (25). However,
this reaction, as well as many other electro-
chemical reactions, has to be coupled to another
sacrificial half-reaction, e.g., proton reduction
to form hydrogen, at the counterelectrode
(23, 24). In addition to this limitation, current
protocols can often be further limited by the
use of complex reaction setups including ex-
pensive metal electrodes (23, 24).
Vicinal dibromides and dichlorides are important commodity chemicals and indispensable synthetic
intermediates in modern chemistry that are traditionally synthesized using hazardous elemental chlorine
and bromine. Meanwhile, the environmental persistence of halogenated pollutants necessitates improved
approaches to accelerate their remediation. Here, we introduce an electrochemically assisted shuttle (e-shuttle)
paradigm for the facile and scalable interconversion of alkenes and vicinal dihalides, a class of reactions that
can be used both to synthesize useful dihalogenated molecules from simple alkenes and to recycle waste
material through retro-dihalogenation. The reaction is demonstrated using 1,2-dibromoethane, as well as
1,1,1,2-tetrachloroethane or 1,2-dichloroethane, to dibrominate or dichlorinate, respectively, a wide range of
alkenes in a simple setup with inexpensive graphite electrodes. Conversely, the hexachlorinated persistent
pollutant lindane could be fully dechlorinated to benzene in soil samples using simple alkene acceptors.
We envisaged that consecutive paired elec-
trolysis (27) involving a domino reduction-
oxidation cascade (28, 29), a class of ideal yet
comparatively rare electrochemical reactions
in which both electrodes are used in the de-
sired transformation, could provide a path to
reversible, electrochemically mediated shuttle
reactions (e-shuttle). We surmised that the re-
versible cleavage of two strong carbon-halogen
bonds through a controlled electron-transfer
process initiated by a simultaneous, simple re-
duction and oxidation of key intermediates at
the cathode and anode, respectively, would un-
lock this transformation (Fig. 1, C and D). In
our hypothesis, the single-electron reduction
of the dihalide at the cathode releases the
X– anion and generates the carbon radical 1,
which is almost instantly reduced again to gen-
erate a carbanion (30). As a central design,
the subsequent selective loss of the second
X– instead of a hydride breaks the C−X bond,
releasing the alkene compound. Considering
that a halide anion is a much better leaving
group than a hydride, the competing un-
desired b–H elimination, which is often the
preferred pathway when alkyl-transition metal
complexes are involved as intermediates, can
be effectively suppressed by this electrochem-
ical approach. The subsequent oxidation of
X– at the anode followed by reaction with the
alkene delivers the desired product, which
closes the cycle by reestablishing the C−X
bonds in a fully isodesmic process. Precise
control of the potential applied on the electrodes
and the highly tunable cell voltage would
make this strategy modular and versatile with
regard to the group transferred. This is an ad-
vantage over the organometallic strategy, in
which each shuttle reaction relies on a com-
pletely different combination of metal and
catalyst requiring independent optimization
campaigns (15).
icinal dibromides and dichlorides have
found widespread applications as flame
retardants, pest control agents, polymers,
and pharmaceuticals (1, 2). They also
serve as versatile synthetic intermedi-
hazardous reagents (8–15) such as HCN (9).
However, catalytic and reversible transfer re-
actions have so far been limited to alkene
monofunctionalization (16) reactions, which
usually involve the transfer of an HX molecule
(8, 15). By contrast, the synthetically appealing
simultaneous transfer of two functional groups
in a catalytic reversible transfer difunctional-
ization process has remained largely elusive
despite the vast synthetic potential of these
reactions in organic synthesis. In particular,
reactions involving the formal transfer of ex-
tremely reactive and corrosive molecules such
as Cl2 (17, 18) and Br2 from easier-to-handle,
stable bulk chemicals such as inexpensive 1,2-
dichloroethane and 1,2-dibromoethane would
be highly desirable because of the widespread
synthetic applications of dihalogenated mole-
cules in flame retardants, pesticides, materials,
and natural products (1, 2, 19) (Fig. 1A). The
inherent reversibility of such a shuttle reac-
tion would further unlock the facile retro-
dihalogenations of end-of-life halogenated
products for remediation (Fig. 1A).
The challenge in developing transfer difunc-
tionalizations such as transfer dihalogenations
originates from the catalytic approach gener-
ally used in shuttle catalysis. Transfer hydro-
functionalizations such as hydrocyanation (9)
rely on the intermediacy of an alkyl-metal
complex that readily undergoes fast and re-
versible b-hydride elimination, thus triggering
the transfer of a hydrogen atom alongside the
desired functional group (15) (Fig. 1B). Unfor-
tunately, the ease of b-hydride elimination
makes the selective, competitive elimination
of other synthetically useful groups challeng-
ing (20). Furthermore, while b-hydride elimi-
nation is a fast and reversible process, the
subsequent migratory reinsertion of an alkene
into a metal-halogen bond is often kinetically
and thermodynamically disfavored because
of the high stability of these types of bonds (6).
Thus, a mechanistically distinct approach to
V
ates in organic chemistry because of the inher-
ent reactivity of carbon–halogen bonds (3, 4).
Despite these attractive features, the prepara-
tion of dihalogenated molecules still mainly
relies on the use of highly reactive and cor-
rosive halogenating reagents such as Cl2 and
Br2, which are hazardous compounds to trans-
port, store, and handle (4–7). Two general strat-
egies have been commonly used to avoid the
direct use of Cl2 and Br2. The first strategy
makes use of carrier reagents such as Et4NCl3
or pyridinium tribromide as bench-stable sur-
rogates. Despite their increasing stability, they
still require the use of X2 reagents for their
syntheses and tend to be unstable and corro-
sive themselves because they are designed to
readily release the corresponding X2 reagents
(5–7). The second strategy relies on the in situ
generation of the active halogenating species
from the reaction between halides and strong
oxidants, a feature that can limit the func-
tional group (e.g., alcohols) compatibility of
these reactions (5–7). The use of strong oxidants
also creates thermodynamic challenges for the
development of the reverse reactions, retro-
dihalogenations, that could be applied to re-
mediation of persistent halogenated pollutants.
Transfer hydrofunctionalization proceeding
through a shuttle catalysis (8) paradigm has
emerged as a powerful and versatile strategy
to reversibly functionalize and defunctionalize
organic molecules without using or releasing
1Laboratory of Organic Chemistry, Department of Chemistry
and Applied Biosciences, ETH Zürich, Zürich, Switzerland.
2Department of Chemistry, Johannes Gutenberg University,
Mainz, Germany.
*These authors contributed equally to this work.
†Corresponding author. Email: bill.morandi@org.chem.ethz.ch
(B.M.); waldvogel@uni-mainz.de (S.R.W.)
At the outset of our investigations, a transfer
dibromination was optimized in an undivided
cell using inexpensive isostatic graphite as the
Dong et al., Science 371, 507–514 (2021)
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electrode material under constant current
conditions at room temperature, a reaction
setup easily accessible to nonspecialized labo-
ratories. 1,2-Dibromoethane (DBE) was selected
as a formal Br2 donor because it is an inex-
pensive and stable reagent, produced on a
bulk scale, that would release gaseous ethyl-
ene as a by-product, thus providing a driving
force for the shuttle process. Most commercial
suppliers offer this reagent at an even lower
price (per mole of Br2 equivalents) than Br2
itself, presumably reflecting the challenges
and costs inherent to transporting and storing
the volatile and corrosive Br2 (31). Optimal re-
sults were obtained with 5 equivalents of
Fig. 1. Reaction design and challenges of transfer difunctionalization. (A) Notable examples of compounds carrying vicinal dihalide moieties. (B) Transfer
hydrofunctionalization and challenges in the development of transfer difunctionalization. (C) Electrolysis-enabled redox-neutral shuttle reaction (e-shuttle).
(D) Reaction design showing consecutive paired electrolysis.
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1,2-dibromoethane as the Br2 donor, 1 volume
percent (vol %) 1,1,1,3,3,3-hexafluoroisopropanol
(HFIP) as a key additive (32), and 2 equivalents
of Et4NBF4 as electrolyte in acetonitrile, pro-
viding the targeted 1,2-dibromide 2 in 84%
yield (measured by integration of nuclear mag-
netic resonance spectra) when 3 F of electricity
with respect to 1-dodecene was applied (Fig. 2).
As indicated by cyclic voltammetry (CV)
studies, the HFIP facilitates the reduction of
the DBE donor and suppresses the undesired
and unproductive reductive oligomerization
Fig. 2. Scope of the Br2 and
Br−SPh shuttle reactions.
All yields are isolated yields of
the products. (A) CV studies.
(B) Scope of the Br2 shuttle
reaction. (C) Scale-up reaction
in a beaker cell. (D) Scope of
the Br−SPh shuttle reaction.
*1 F equals ~62 min of
electrolysis time. †Conditions
for CV studies: A 5 mM solution
of 1,2-DBE and 1-dodecene in
MeCN using NEt4BF4 (0.2 M) as
the supporting electrolyte at a
graphite electrode with and
without 1 vol % HFIP as the
additive. ‡(E)-4-octene used
as the starting material.
§1 F equals ~31 min of
electrolysis time. r.t., room
temperature; FcH, ferrocene;
r.r., regioisomeric ratio.
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A
B
C
Fig. 3. Scope of the Cl2 and Cl−SPh shuttle reactions. Here, 1 F equals ~81 min
of electrolysis time. All yields are isolated yields of the products unless otherwise
noted. (A) Cl2 donor optimization. (B) Scope of the Cl2 shuttle reaction.
(C) Preliminary examples of the Cl−SPh shuttle reaction. *1H-NMR yield with
mesitylene as the internal standard. †Neat DCE (0.1 M) as the donor and
1-dodecene (1 equivalent) as the acceptor. ‡Redox potential (V versus SCE)
measured for the first reduction peak at 0.2 Vs−1 for polychlororethanes (2 mM)
in DMF + 0.1 M (C3H7)4NBF4 at a glassy carbon electrode according to (38).
§Neat DCE (0.1 M) as the donor. ¶Reaction performed in MeCN (0.1 M) with
1,1,1,2-tetrachloroethane as the donor. #(E)-prop-1-en-1-ylbenzene used as the
starting material. **(Z)-prop-1-en-1-ylbenzene used as the starting material.
d.r., diastereomeric ratio.
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and/or polymerization of alkene acceptors at
the cathode (see Fig. 2A and figs. S31 and S32
for more details). The supporting electrolyte
can be easily crystallized from the reaction
mixture to be recycled.
Using this protocol, a broad range of un-
activated terminal alkenes (2−11) were readily
converted to the corresponding dibromide
product in modest to good yields. The reac-
tion conditions were compatible with a large
variety of functional groups such as amide (3),
ester (4), free carboxylic acid (5), primary al-
cohol (6), sulfone (7), and bromide (8). Only a
small amount of the alcohol group oxidation
to aldehyde was observed, confirming the
Fig. 4. Application of e-shuttle reactions. (A) Persistent polychlorinated waste degradation through e-shuttle. (B) Generality of lindane waste degradation.
(C) Large-scale degradation of lindane. (D) Remediation of lindane-contaminated soil. *Isolated yield. †1 F equals ~81 min of electrolysis time. ‡Yield measured by
gas chromatography using mesitylene or anisole as the internal standard. §Lindane was extracted with MeCN before degradation.
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mild nature of the reaction conditions. Activ-
ated alkenes, such as styrene (12–15) and vinyl
silane (16 and 17), proved to be suitable sub-
strates as well, albeit giving slightly lower
yields because of undesired alkene oligomer-
ization. Although hexa-1,5-diene underwent
twofold 1,2-dibromination to yield the tetra-
brominated product 18 in acceptable yield,
selective mono-1,2-dibromination was observed
for several other unconjugated dienes (19 and
20). (E)-4-Octene was smoothly dibrominated
to produce the meso-dibromide 21 as the single
diastereomer. To demonstrate the scalability
and robustness of this e-shuttle process, the
transfer bromination of 1-dodecene was read-
ily scaled up to a 250-ml beaker cell from a
10-ml reaction vial to give 6.57 g (80% yield)
of product 2 under otherwise identical reac-
tion conditions (Fig. 2C).
Taking advantage of the reversible elim-
ination of a −SR group (33), we could next
also develop a transfer bromothiolation of
alkenes to prepare 1,2-bromothioether deri-
vatives, which are valuable synthetic inter-
mediates usually accessed through multistep
synthesis involving highly reactive RSBr re-
agents (34, 35). Several terminal alkenes were
successfully converted to the targeted bromo-
thioether product under otherwise iden-
tical conditions, taking 2-bromoethyl phenyl
sulfide (5 equivalents) as the PhS−Br donor
(Fig. 2D). The lower yields arose from com-
peting formation of vicinal disulfides and
RS−SR, as well as alkene oligomerization.
The ester (23) functional group was com-
patible. An interrupted shuttle reaction took
place when pent-4-en-1-ol and pent-4-enoic
acid were used as the substrates, delivering
the cyclic ether (24) or lactone derivatives
(25) through subsequent intramolecular nu-
cleophilic attack, demonstrating the meth-
od’s potential for the development of cascade
reactions.
We next explored a transfer dichlorination
reaction (Fig. 3). 1,2-Dichloroethane (DCE) was
selected as the donor because it is an inexpen-
sive bulk chemical (20 million tons/year) that
is produced as a central intermediate in poly-
vinylchloride (PVC) production using the ex-
cess of Cl2 gas generated during the Chlor-alkali
electrolysis process (36). The desired dichloride
28 was obtained in 40% yield when 5 mol % of
manganese(II) chloride tetrahydrate was intro-
duced as a mediator (25) using an otherwise
identical electrochemical setup to the dibro-
mination protocol. The yield was further in-
creased to 70% when DCE (~125 equivalents)
was used as the solvent (37). Although this
procedure was efficient for a wide set of ter-
minal alkenes (28–34; Fig. 3B), it failed for
more challenging 1,1,2-trisubstituted alkene
26 (Fig. 3A), a feature largely attributable to
the undesired 1,2-dechlorinative decomposi-
tion of the product 27 and alkene oligomeriza-
tion of the starting material through cathodic
reduction. We reasoned that these two chal-
lenges could be smoothly addressed by choos-
ing a more suitable dichloride donor. On the
basis of the known reduction potentials of a
large set of simple chlorinated compounds
(38), we hypothesized that polychlorinated C2
donors, which are more readily reduced, should
lead to a more favorable reaction outcome.
Experimentally, an excellent correlation be-
tween the reduction potential of a series of
donors was indeed observed, leading to the
identification of 1,1,1,2-tetrachloroethane, a
stable, noncorrosive compound, as the reagent
of choice, affording the desired dichloride pro-
duct 27 in 90% nuclear magnetic resonance
(NMR) yield (Fig. 3A). Using this procedure,
a series of monosubstituted, disubstituted, and
trisubstituted alkenes participated smoothly
in the 1,2-transfer dichlorination reaction, with
free alcohol (29, 35, and 37), ester (30), imide
(32), phosphonate (33), sulfone (34), and Ts-
and Boc-protected amine moieties (38 and 39)
proving compatible. An internal alkyne (37)
was even partially compatible with the reac-
tion conditions despite the minor formation
of unidentified by-products. Various styrene-
derived alkenes were converted to the corre-
sponding 1,2-dichlorides in good to excellent
yield (42–52), leaving the Br, Cl, CN, CF3,
CHO, and COOH functional groups untouched.
Indene was diastereoselectively transformed
into trans-1,2-dichloride 50 (diastereomeric
ratio > 19:1). Both (E)- and (Z)-1-phenylpropene
were converted to the anti-dichloride 51 in
similarly high diastereoselectivity. The 1,2-
dichloride compound 52, bearing a reactive
benzylic tertiary C−Cl bond, was prepared in
good yield from a-methylstyrene. Several other
activated alkenes, such as the silyl- and ester-
substituted alkenes, also proved to be viable
substrates to deliver the dichloride products
(53–56), in particular, methyl cinnamate was
converted to the 1,2-dichloride 56 in an excel-
lent diastereomeric ratio (>19:1). To our de-
light, preliminary experiments showed that
this protocol can be readily extended to the
1,2-chlorothiolation transfer reaction using the
commercially available 2-chloroethyl phenyl
sulfide (10 equivalents) as the donor (Fig. 3C).
The lower yield can be explained by the un-
desired formation of RS−SR species as well as
substrate oligomerization.
ample is lindane [gamma-hexachlorocyclohexane
(HCH)], a compound that was once used world-
wide as an effective broad-spectrum insecticide
in crop protection, which is now classified as a
persistent organic pollutant because of its high
toxicity and high persistency in the environ-
ment (39–42). Global quantities of HCH wastes
still present in the environment range between
4 and 7 million tons worldwide, highlighting
the pressing challenge of finding methods to
recycle and remove this compound from con-
taminated soils (39). We thus questioned wheth-
er this waste material, which, among other
chemical and biological approaches (40), can
only be inefficiently degraded through normal
electrochemical recycling methods (43–45),
could be efficiently retro-dihalogenated using
our e-shuttle strategy (Fig. 4A). Indeed, lindane,
through three successive retro-dichlorination
events, successfully transferred its six chlorine
atoms to an acceptor alkene to form benzene,
the fully dechlorinated by-product of lindane,
alongside a dichlorinated alkane. Five illus-
trative alkene examples gave excellent yields
up to 89% (>95% gas chromatography yield
of benzene; Fig. 4B), demonstrating the
generality of this process and the possibil-
ity of accessing a wide variety of potentially
useful chemicals. A scale-up experiment (87.5
mmol of alkene) further showcased the effi-
ciency of the retro-dichlorination process
(Fig. 4C). The exceptional functional group
tolerance of our e-shuttle strategy made us next
question whether we could successfully retro-
dichlorinate lindane–contaminated soils
through a transfer dichlorination reaction
(Fig. 4D). In theory, such a process could lead
to a new avenue to chemically remediate highly
contaminated soils, which are mainly caused
by leachates of improper disposal at landfilling
or dump sites (39, 40, 42), through simulta-
neous synthesis of commercially relevant di-
chlorinated chemicals. This could provide an
alternative to current industrial approaches
that focus on the generation of HCl from
chlorinated waste (42).
Artificially contaminated soils are common-
ly used as models in environmental chemistry
to perform proof-of-concept chemical reme-
diation experiments (46). Therefore, to mimic
the composition of soils contaminated by high
concentration of HCH, three soil samples from
different locations near our university cam-
pus, i.e., roadside, flower field, and farmland,
were collected and homogeneously mixed
with commercially available lindane. The
50 weight % (wt %) lindane–contaminated soil
could be used directly in the reaction without
any preextraction or filtration, delivering both
the benzene and dichloride product in excel-
lent yields and high purity (Entries 1 to 3; Fig.
4D), a result comparable to the experiments
using pure lindane (Entry 5; Fig. 4D). This
result shows that our degradation process is
In contrast to traditional halogenation meth-
ods, the inherent reversibility of the e-shuttle
strategy offers a platform to develop retro-
dihalogenation reactions. Given the environ-
mental persistence of several halogenated
compounds produced at commodity scale,
such as flame retardants and insecticides,
e-shuttle could facilitate their recycling and
valorization through retro-dihalogenations,
which could ultimately lead to a circular econo-
my for these important chemicals. A notable ex-
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compatible with the biological and mineral
impurities present in three different soil types.
Although the exact composition of environ-
mentally relevant contaminated soils might
differ from our samples (39, 41, 42), we never-
theless believe that these positive preliminary
results using a variety of soil samples sup-
port the feasibility of this approach. A much
lower lindane-soil ratio of 1 wt % was extracted
with the reaction solvent before the degra-
dation to also afford good yields for both
benzene (76%) and dichloride (76%, Entry 4;
Fig. 4D). This alternative preextraction proto-
col acts as a further proof-of-concept that
might help in the design of larger-scale re-
mediation processes in which undesired soil
contamination with electrolytes and Mn cata-
lysts can be prevented. The large-scale feasi-
bility of an extraction approach has been
demonstrated by the successful treatment of
~70,000 tons of HCH-contaminated soils in
the Netherlands in a full-scale soil-washing
plant, which achieved HCH removal efficiency
of >99.7% (42).
20. R. H. Crabtree, The Organometallic Chemistry of the Transition
Metals (Wiley, ed. 5, 2009).
21. M. Yan, Y. Kawamata, P. S. Baran, Chem. Rev. 117,
13230–13319 (2017).
22. J. C. Siu, N. Fu, S. Lin, Acc. Chem. Res. 53, 547–560
(2020).
23. J. L. Röckl, D. Pollok, R. Franke, S. R. Waldvogel, Acc. Chem. Res.
53, 45–61 (2020).
24. A. Wiebe et al., Angew. Chem. Int. Ed. 57, 5594–5619
(2018).
25. N. Fu, G. S. Sauer, S. Lin, J. Am. Chem. Soc. 139, 15548–15553
(2017).
26. Y. Yuan et al., iScience 12, 293–303 (2019).
27. Y. Mo et al., Science 368, 1352–1357 (2020).
28. M. F. Hartmer, S. R. Waldvogel, Chem. Commun. 51,
16346–16348 (2015).
29. D. Pollok, S. R. Waldvogel, Chem. Sci. 11, 12386–12400 (2020).
30. J. Casanova, L. Eberson, “Electrochemistry of the carbon–
halogen bond,” in The Chemistry of The Carbon-Halogen Bond:
Part 1, S. Patai, ed. (Wiley, 1973), pp. 979–1047.
31. D. M. Hill, “Safety review of bromine-based electrolytes for
energy storage applications,” Report 1 (2018); http://
energystorageicl.com/wp-content/uploads/2018/04/DNV-GL-
Safety-Review-of-Bromine-Based-Electrolytes-for-Energy-
Storage-Applications.pdf.
32. L. Schulz, S. R. Waldvogel, Synlett 30, 275–286 (2019).
33. S. E. Denmark, W. R. Collins, M. D. Cullen, J. Am. Chem. Soc.
131, 3490–3492 (2009).
34. E. Schneider, Chem. Ber. 84, 911–916 (1951).
35. J. Drabowicz, P. Kiełbasiński, M. Mikołajczyk, “Synthesis of
sulphenyl halides and sulphenamides,” in Sulfenic Acids and
Derivatives, S. Patai, ed. (Wiley, 1990), pp. 221–292.
36. C. Hoffmann, J. Weigert, E. Esche, J.-U. Repke, Chem. Eng. Sci.
214, 115358 (2020).
59. K. M. Redies, T. Fallon, M. Oestreich, Organometallics 33,
3235–3238 (2014).
60. R. Campagne, F. Schäkel, R. Guillot, V. Alezra, C. Kouklovsky,
Org. Lett. 20, 1884–1887 (2018).
61. D. Lexa et al., J. Am. Chem. Soc. 112, 6162–6177 (1990).
62. L. Benati, P. C. Montevecchi, P. Spagnolo, Tetrahedron 49,
5365–5376 (1993).
63. X. Marset, G. Guillena, D. J. Ramón, Chem. Eur. J. 23,
10522–10526 (2017).
64. R. M. Denton, X. Tang, A. Przeslak, Org. Lett. 12, 4678–4681
(2010).
65. A. J. Cresswell, S. T.-C. Eey, S. E. Denmark, Nat. Chem. 7,
146–152 (2015).
66. J. C. Sarie, J. Neufeld, C. G. Daniliuc, R. Gilmour, ACS Catal. 9,
7232–7237 (2019).
67. H. Egami et al., J. Org. Chem. 81, 4020–4030 (2016).
68. V. Wedek, R. Van Lommel, C. G. Daniliuc, F. De Proft,
U. Hennecke, Angew. Chem. Int. Ed. 58, 9239–9243
(2019).
69. E. W. Tan, B. Chan, A. G. Blackman, J. Am. Chem. Soc. 124,
2078–2079 (2002).
70. J. Wei, S. Liang, L. Jiang, Y. Mumtaz, W.-B. Yi, J. Org. Chem.
85, 977–984 (2020).
71. L. Benati, L. Capella, P. C. Montevecchi, P. Spagnolo,
Tetrahedron 50, 12395–12406 (1994).
72. P. Sanllehí et al., Chem. Commun. 53, 5441–5444
(2017).
73. J. M. Lopchuk et al., J. Am. Chem. Soc. 139, 3209–3226
(2017).
74. K. Yuan, J.-F. Soulé, V. Dorcet, H. Doucet, ACS Catal. 6,
8121–8126 (2016).
75. J. C. Siu, J. B. Parry, S. Lin, J. Am. Chem. Soc. 141, 2825–2831
(2019).
76. R. L. Nyland II, Y. Xiao, P. Liu, C. L. Freel Meyers, J. Am. Chem.
Soc. 131, 17734–17735 (2009).
77. K. Yasui, K. Fugami, S. Tanaka, Y. Tamaru, J. Org. Chem. 60,
1365–1380 (1995).
Collectively, these preliminary results serve
as a proof-of-principle for the direct reme-
diation of lindane-contaminated soils using
e-shuttle methodology.
37. Y. Liang, F. Lin, Y. Adeli, R. Jin, N. Jiao, Angew. Chem. Int. Ed.
58, 4566–4570 (2019).
38. B. Huang, A. A. Isse, C. Durante, C. Wei, A. Gennaro,
Electrochim. Acta 70, 50–61 (2012).
39. J. Vijgen, B. de Borst, R. Weber, T. Stobiecki, M. Forter, Environ.
Pollut. 248, 696–705 (2019).
40. P. Bhatt, M. S. Kumar, T. Chakrabarti, Crit. Rev. Environ. Sci.
Technol. 39, 655–695 (2009).
78. D. Song, S. Cho, Y. Han, Y. You, W. Nam, Org. Lett. 15,
3582–3585 (2013).
79. Y.-Y. Ren, X. Zheng, X. Zhang, Synlett 29, 1028–1032
REFERENCES AND NOTES
1. K. L. Kirk, “Persistent polyhalogenated compounds:
biochemistry, toxicology, medical applications, and associated
environmental issues,” in Biochemistry of the Elemental
Halogens and Inorganic Halides (Springer, 1991), pp. 191–238.
2. M. M. Häggblom, I. D. Bossert, “Halogenated organic
compounds: A global perspective,” in Dehalogenation: Microbial
Processes and Environmental Applications (Springer, 2003)
pp. 3–29.
3. S. Patai, The Chemistry of The Carbon–Halogen Bond:
Part 1 (Wiley, 1973).
4. I. Saikia, A. J. Borah, P. Phukan, Chem. Rev. 116, 6837–7042
(2016).
5. M. Eissen, D. Lenoir, Chem. Eur. J. 14, 9830–9841 (2008).
6. A. J. Cresswell, S. T.-C. Eey, S. E. Denmark, Angew. Chem. Int.
Ed. 54, 15642–15682 (2015).
7. W.-J. Chung, C. D. Vanderwal, Angew. Chem. Int. Ed. 55,
4396–4434 (2016).
8. B. N. Bhawal, B. Morandi, ACS Catal. 6, 7528–7535 (2016).
9. X. Fang, P. Yu, B. Morandi, Science 351, 832–836 (2016).
10. X. Fang, B. Cacherat, B. Morandi, Nat. Chem. 9, 1105–1109
(2017).
11. S. K. Murphy, J.-W. Park, F. A. Cruz, V. M. Dong, Science 347,
56–60 (2015).
12. D. A. Petrone et al., J. Am. Chem. Soc. 139, 3546–3557
(2017).
13. W. Chen, J. C. L. Walker, M. Oestreich, J. Am. Chem. Soc. 141,
1135–1140 (2019).
14. P. Yu, A. Bismuto, B. Morandi, Angew. Chem. Int. Ed. 59,
2904–2910 (2020).
15. B. N. Bhawal, B. Morandi, Angew. Chem. Int. Ed. 58,
10074–10103 (2019).
16. M. Beller, J. Seayad, A. Tillack, H. Jiao, Angew. Chem. Int. Ed.
43, 3368–3398 (2004).
17. K. Sakai, K. Sugimoto, S. Shigeizumi, K. Kondo, Tetrahedron
Lett. 35, 737–740 (1994).
18. M. L. Ho, A. B. Flynn, W. W. Ogilvie, J. Org. Chem. 72, 977–983
(2007).
19. G. W. Gribble, Acc. Chem. Res. 31, 141–152 (1998).
(2018).
41. K. Walker, D. A. Vallero, R. G. Lewis, Environ. Sci. Technol. 33,
4373–4378 (1999).
ACKNOWLEDGMENTS
We thank M. Zesiger, the NMR service, the Molecular and
Biomolecular Analysis Service (MoBiAS), and ETH Zürich for
technical assistance; SusInnoScience (JGU Mainz) for support;
S. Makai for assistance with gas chromatography–mass
42. M. Vega, D. Romano, E. Uotila, “Lindane (persistent organic
pollutant) in the EU” [Directorate General for Internal Policies.
Policy Department C: Citizens’ Rights and Constitutional
Affairs. Petitions (PETI) PE 571.398, 2016].
43. S. Rondinini, A. Vertova, “Electroreduction of halogenated
organic compounds,” in Electrochemistry for the Environment,
C. Comninellis, G. Chen, ed. (Springer, 2010), pp. 279–306.
44. J. P. Merz, B. C. Gamoke, M. P. Foley, K. Raghavachari,
D. G. Peters, J. Electroanal. Chem. 660, 121–126 (2011).
45. E. T. Martin, C. M. McGuire, M. S. Mubarak, D. G. Peters,
Chem. Rev. 116, 15198–15234 (2016).
46. E. Morillo, J. Villaverde, Sci. Total Environ. 586, 576–597
(2017).
47. G. R. Fulmer et al., Organometallics 29, 2176–2179
(2010).
48. J. Liu, Q. Ren, X. Zhang, H. Gong, Angew. Chem. Int. Ed. 55,
15544–15548 (2016).
49. A. K. Macharla, R. C. Nappunni, N. Nama, Tetrahedron Lett. 53,
1401–1405 (2012).
50. S. Lethu, S. Matsuoka, M. Murata, Org. Lett. 16, 844–847
(2014).
51. J. Long et al., Synlett 30, 181–184 (2019).
52. G. W. Kabalka, K. Yang, N. K. Reddy, C. Narayana, Synth. Commun.
28, 925–929 (1998).
53. K. Yubata, H. Matsubara, Tetrahedron Lett. 60, 1001–1004
(2019).
54. X. Xia, P. H. Toy, Beilstein J. Org. Chem. 10, 1397–1405
(2014).
55. W. Chen et al., Chem. Eur. J. 22, 9546–9550 (2016).
56. A. Chassepot et al., Chem. Mater. 24, 930–937 (2012).
57. N. S. Martins, E. E. Alberto, New J. Chem. 42, 161–167 (2018).
58. W. E. Billups et al., J. Org. Chem. 67, 4436–4440
(2002).
spectrometry headspace analysis and helpful discussions; E. Falk
for reproducing one of the lindane-soil experiments; S. Makai,
E. Falk, B. Bhawal, and T. Delcaillau for sharing chemicals; and the
whole Morandi group for critical proofreading of this manuscript.
Funding: This project received funding from the European
Research Council under the European Union's Horizon 2020
research and innovation program (Shuttle Cat, Project ID: 757608)
and the ETH Zürich. X.D. acknowledges the Marie Skłodowska-Curie
Action (HaloCat, Project ID: 886102) for a postdoctoral fellowship.
J.L.R. is a recipient of a DFG fellowship through the Excellence
Initiative by the Graduate School Materials Science in Mainz
(GSC 266). Author contributions: B.M. and X.D. conceived the
project. X.D. and J.L.R. designed and performed all the synthetic
studies. S.W. and B.M. supervised the research. All authors
contributed to the writing and editing of the manuscript.
Competing interests: The authors declare no competing interests.
Data and materials availability: All experimental data are
available in the main text or the supplementary materials.
SUPPLEMENTARY MATERIALS
science.sciencemag.org/content/371/6528/507/suppl/DC1
Materials and Methods
Figs. S1 to S41
Tables S1 to S16
NMR Spectra
References (47−79)
16 October 2020; accepted 30 December 2020
10.1126/science.abf2974
Dong et al., Science 371, 507–514 (2021)
29 January 2021
7 of 7

Merging shuttle reactions and paired electrolysis for reversible vicinal dihalogenations
Xichang Dong, Johannes L. Roeckl, Siegfried R. Waldvogel and Bill Morandi
Science 371 (6528), 507-514.
DOI: 10.1126/science.abf2974
Shuttling halide pairs back and forth
The transfer of adjacent hydrogens from a saturated to an unsaturated organic compound is a fairly common
reaction. However, analogs that shuttle two heavy atoms back and forth are much harder to catalyze. Dong et al. report
an electrochemical approach that transfers a pair of adjacent chlorines or bromines from an alkyl compound to an olefin.
The method could help to remediate halogenated pollutants while concurrently producing fine chemicals.
Science, this issue p. 507
ARTICLE TOOLS
http://science.sciencemag.org/content/371/6528/507
SUPPLEMENTARY
MATERIALS
http://science.sciencemag.org/content/suppl/2021/01/27/371.6528.507.DC1
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