Nickel-Catalyzed Photodehalogenation of Aryl Bromides

Article abstract of DOI:10.1055/a-1457-2399

Herein, we describe a Ni-catalyzed photodehalogenation of aryl bromides under visible-light irradiation that utilizes tetrahydrofuran as hydrogen source. The protocol obviates the need for exogeneous amine reductants or photocatalysts and is characterized by its simplicity and broad scope, including challenging substrate combinations.

Full text of DOI:10.1055/a-1457-2399

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Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart
2021, 32, A–D
cluster
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Nickel in Catalysis
B. Higginson et al.
Cluster
Synlett
Nickel-Catalyzed Photodehalogenation of Aryl Bromides
Bradley Higginsona,b
Jesus Sanjosé-Ordunaa
Yiting Gua
Ruben Martin*a,c
this work
H(D)
Br
Ni
R
R
THF or THF-d8
25 examples
up to 90%
wide substrate scope
no reductant & no photocatalyst
a Institute of Chemical Research of Catalonia (ICIQ), Av. Paisos
Catalans 16, 43007, Tarragona, Spain
rmartinromo@iciq.es
b Departament de Química Analítica i Química Orgànica, Uni-
versitat Rovira i Virgili, c/Marcel·lí Domingo, 1, 43007 Tarrago-
na, Spain
c ICREA, Passeig Lluís Companys, 23, 08010 Barcelona, Spain
Published as part of the Cluster
Modern Nickel-Catalyzed Reactions
Corresponding Author
Received: 23.02.2021
Accepted after revision: 21.03.2021
Published online: 21.03.2021
niques make use of expensive noble-metal catalysts, exoge-
nous reductants, and/or high temperatures (Scheme 1, top
right).4 Electrochemistry has also made some significant
progress in this arena, however, it is not without its limita-
tions.5 Driven by the renewed interest in photoredox reac-
tions and its unique ability to access open-shell reaction in-
termediates via photoinduced electron-transfer events,6 it
comes as no surprise that catalytic photodehalogenation re-
actions have recently gained considerable momentum
(Scheme 1, middle). However, the disparity between the re-
duction potential of aryl halides and the available portfolio
of photocatalysts makes these techniques not as trivial as
one might initially anticipate.1,3
DOI: 10.1055/a-1457-2399; Art ID: st-2021-r0065-c
Abstract Herein, we describe a Ni-catalyzed photodehalogenation of
aryl bromides under visible-light irradiation that utilizes tetrahydrofuran
as hydrogen source. The protocol obviates the need for exogeneous
amine reductants or photocatalysts and is characterized by its simplici-
ty and broad scope, including challenging substrate combinations
Key words nickel, photochemistry, dehalogenation, reduction, deu-
teration
Aryl halides rank amongst the most versatile synthetic
handles in organic chemistry. Whilst a myriad of C–C and
C–heteroatom bond-forming reactions have been devel-
oped using aryl halides as coupling counterparts, the proto-
dehalogenation reaction remains a much less-explored en-
deavor.1 These processes are of significant industrial rele-
vance, as polyhalogenated entities such as polybrominated
diphenyl ethers (PBDE) are known persistent organic pol-
lutants, flame retardants, and health hazards that have
been banned by the Stockholm convention.2 Therefore, the
synthetic community has been challenged to design effi-
cient, reliable, and practical catalytic dehalogenation tech-
niques. Whilst radical pathways based on the utilization of
tin hydride or metal–halogen exchange techniques with
stoichiometric amounts of metal complexes have become
routine in the dehalogenation arena (Scheme 1, top left),3
the formation of toxic byproducts, the need for stoichio-
metric reductants, and/or the poor functional group com-
patibility reinforce a change in strategy. In recent years,
transition-metal-catalyzed reductions of aryl halides have
offered an alternative solution for promoting protodehalo-
genation reactions. Unfortunately, however, these tech-
conventional manifolds
(X = halogen)
path a
R3SnH
or
path b
X
H
X
catalyst
R
R
R
reductant
R–[M], then H+
toxic byproducts
noble metals
high temperatures
external reductants
cryogenic temperatures
low chemoselectivity
photochemical settings
(PC = photocatalyst)
M
PC
X
H
external photocatalyst
sacrificial NR3 reductant
no D-incorporation
R
R
reductant (NR3)
light
this work: Ni-catalyzed photodehalogenation of aryl bromides
this work
H(D)
Br
no photocatalyst
solvent as H-donor
wide scope
Ni
R
R
THF or THF-d8
Scheme 1 Catalytic photodehalogenation techniques
© 2021. Thieme. All rights reserved. Synlett 2021, 32, A–D
Georg Thieme Verlag KG, Rüdigerstraße 14, 70469 Stuttgart, Germany

B
B. Higginson et al.
Cluster
Synlett
In recent years, high-energy UV or powerful blue
lamps,7 dual-catalytic platforms,8 or novel photocatalysts
designed to reach the appropriate range of redox potentials
of aryl halides have been employed to trigger catalytic pho-
todehalogenation reactions.9 In most instances, however, an
exogenous amine reductant is required to maintain the re-
ductive quenching cycle of these techniques (Scheme 1,
middle). Recently, Chen has shown the viability for enabling
a photocatalytic reduction of aryl halides using noble palla-
dium catalysts in combination with i-PrOH via hydrogen
atom transfer (HAT).10 Given the inherent ability of nickel
catalysts to trigger single-electron-transfer processes and
the ability to merge its unique properties within the realm
of photoredox catalysis, we wondered whether a Ni-cata-
lyzed photodehalogenation technique of aryl halides in the
absence of sacrificial reductants or stoichiometric metal
sources might be implemented (Scheme 1, bottom). If suc-
cessful, we anticipated that such a technique might not only
offer a complementary approach to related photodehaloge-
nation scenarios and/or Pd-catalyzed approaches, but also
provide new knowledge in synthetic design.
We began our study with the debromination of 4-bro-
moanisole by using THF both as solvent and as hydrogen
donor. Judicious screening of the reaction conditions re-
vealed that a combination of NiI2, 1,4-bis(dicyclohexylphos-
phino)butane (L1), Na2CO3, and CsI under blue light irradia-
tion (451 nm) provided the best results, obtaining 2a in 90%
isolated yield (Table 1, entry 1).11 Ni(COD)2 and Ni(II) salts
other than NiI2 had a deleterious impact on reactivity (en-
tries 2–4). The latter is particularly interesting, thus reveal-
ing a non-negligible influence of the counterion in the reac-
tion outcome. As shown in entries 5 and 6, L1 provided bet-
ter results than its corresponding L2 or L3 analogues, this
could possibly be due to the increased flexibility of L1 in
comparison to L2 and the greatly increased electron density
over L3. In addition, lower yields were found when employ-
ing PCy3 (entry 8) whereas nitrogen-containing ligands did
not afford even traces of 2a. Interestingly, the utilization of
additives other than CsI was detrimental for the reaction to
occur. While control experiments showed that the inclusion
of both light and ligand was critical for success (entry 8), it
is worth noting that significant amounts of 2a were also ob-
served in the absence of CsI (entry 10). Note, however, that
traces of 2a were observed for reactions employing either
dcye or dppe in the absence of CsI, thus not only showing
the subtleties of our system, but also suggesting a complex
behavior exerted by CsI.
Table 1 Screening of Reaction Conditionsa
NiI2 (10 mol%)
L1 (10 mol%)
CsI (20 mol%)
Br
H
PCy2
PCy2
Na2CO3 (1.5 equiv)
MeO
Entry
MeO
L1
THF (0.20 M)
blue LEDs (451 nm), 35 °C
1a
2a
2a (%)
Deviation from standard conditions
98 (90)b
70
75
49
90
40
0
none
1
2
3
4
5
6
7
8
using Ni(COD)2 instead of NiI2
using NiCl2 instead of NiI2
using NiBr2 instead of NiI2
using L2 instead of L1
using L3 instead of L1
using L4 instead of L1
using PCy3 instead of L1
using TBAI instead of CsI
using KI instead of CsI
using CsBr instead of CsI
using Cs2CO3 instead of Na2CO3
no light or no L1
PCy2
L2
L3
PCy2
PPh2
PPh2
23
50
16
19
73
0
9
10
11
12
13
14
no CsI
43
N
N
L4
a Standard conditions: 1a (0.2 mmol), Na2CO3 (0.3 mmol), Ni catalyst (0.02
mmol), ligand (0.03 mmol), CsI (0.03 mmol), THF (1 mL) under blue LED
irradiation (451 nm) at 35 °C for 48 h. GC yields using decane as internal
standard.
b Isolated yield.
a wide number of aryl halides independently of whether
electron-rich or electron-poor substituents were located at
either meta, para, or ortho positions. Likewise, aryl bro-
mides containing esters (2b, 2e, 2m, 2p, 2t), ketones (2d),
amides (2i, 2s), or nitriles (2o) posed no problems. Impor-
tantly, the reaction could be executed on gram scale, ob-
taining 2n in 78% yield. Particularly interesting was the
ability to extend our reaction to heterocyclic cores such as
2q, 2r, or even 2s possessing basic nitrogen donors, as these
motifs might compete with L1 for metal binding. In addi-
tion, the presence of free carboxylic acids (2c) or alcohols
(2l) does not interfere with productive photodehalogena-
tion of the sp2 C–Br site. Importantly, aryl pivalates (2e),
aryl tosylates (2f), or boronic esters (2j) could perfectly be
tolerated, hence providing an additional handle for further
functionalization via classical Pd- or Ni-catalyzed mani-
folds. Attempts to debrominate aryl rings containing iodo or
chloro substituents did not lead to any reduced product. As
illustrated by the successful preparation of 2t and 2u, our
protocol could be applied to low bromine count polybromi-
nated compounds, including the corresponding PBDE with
equal ease. This result is particularly interesting given the
growing interest in promoting efficient and reliable catalyt-
ic dehalogenation techniques of polyhalogenated ethereal
entities.
Next, we turned our attention to evaluating the scope of
the reaction. As evident from the results compiled in
Scheme 2, our photodehalogenation could be applied across
© 2021. Thieme. All rights reserved. Synlett 2021, 32, A–D

C
B. Higginson et al.
Cluster
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NiI2 (10 mol%)
photodehalogenation of polybrominated mixtures of PBDE
L1 (15 mol%)
CsI (20 mol%)
Br
H
H
NiI2 (5 mol%)
L1 (6 mol%)
CsI (30 mol%)
PCy2
PCy2
R
R
Na2CO3 (1.5 equiv)
THF (0.20 M)
blue LEDs (451 nm), 35 °C
Brn
H
L1
1a–u
2a–u
Na2CO3 (1.5 equiv)
O
O
THF (0.20 M)
blue LEDs (451 nm), 35 °C
n = 1, 2 & 3
2u, 51%
2a, 90% (R = OMe)
2b, 63% (R = CO2Me)
2c, 79% (R = CO2H)a
2d, 64% (R = COMe)
2e, 73% (R = OPiv)
2f, 61% (R = OTs)
H
synthesis of deuterated arenes with THF-d8
H
O
NiI2 (5 mol%)
L1 (6 mol%)
CsI (30 mol%)
R
HN
Br
D
BPin
2g, 70% (R = SO2Me)
2h, 53% (R = t-Bu)
R
R
2i, 70%
2j, 78%
Na2CO3 (1.5 equiv)
R1
R2
H
H
THF-d8 (0.20 M)
blue LEDs (451 nm), 35 °C
1
H
2-D
MeO
CO2Me
2k, 68% (R1 = R2 = OMe)
D
D
D
C4H9
O
2m, 60%
2n, 81%, 78%b
2l, 76% (R1 = OMe, R2 = OH)
O
H
TsO
2f-D, 44%
MeO
MeO
H
2v-D, 63%
O
2n-D, 58%
(90%)
(93%)
H
Me
(95%)
CN
H
O
O
S
i-Pr
Scheme 3 Synthetic application
2o, 54%c
2p, 61%
2q, 61%
2r, 80%
H
O
H
porating deuterium atoms into arene backbones. Further
investigations aimed at unravelling the mechanistic intrica-
cies of this reaction and extending this concept to other
coupling partners are currently underway.
O
O
H
N
Me
N
O
O
H
N
N
Me
H
2t, 78%d
2u, 88%d
2s, 54%
Scheme 2 Scope of (hetero)aryl bromides. Reagents and conditions: as
for Table 1, entry 1 for 72 h. a LiOt-Bu (1 equiv); b NiI2 (5 mol%), dcyb (6
mol%), 1n (5 mmol); c CsI (0.08 mmol); d ArBr (0.10 mmol), NiI2 (0.02
mmol), L1 (0.022 mmol), Na2CO3 (0.3 mmol), CsI (0.04 mmol).
Conflict of Interest
The authors declare no conflict of interest.
Funding Information
Encouraged by these results, we next evaluated whether
complex mixtures of mono-, di-, and tribrominated diphe-
nyl ethers could be accomplished with similar ease. As
shown in Scheme 3 (top), this was indeed the case, obtain-
ing the targeted 2u in 51% yield at 5 mol% catalyst loading.
Following up our initial hypothesis of THF being both sol-
vent and hydrogen donor, we anticipated that the utiliza-
tion of THF-d8 might not only provide a useful entry to in-
corporate deuterium atoms into arene backbones, but also
offer a complementary approach to previously reported
procedures employing other deuterated entities.12 As
shown in Scheme 3 (bottom), this turned out to be the case,
and 2f-D, 2n-D, and 2v-D were easily within reach by pro-
moting our photodehalogenation under otherwise identical
reaction conditions, but using THF-d8 instead.
We thank Institut Català d’Investigació Química (ICIQ) and the Fondo
Europeo de Desarrollo Regional (FEDER/MCI, AEI/PGC2018-096839-
B-I00) for financial support. B. H. thanks ‘La Caixa’ Foundation (ID
100010434 and LCF/BQ/DI18/11660031) for a predoctoral fellowship.()
Acknowledgment
We thank ICIQ for institutional support and the members of the Mar-
tin group for useful feedback during the execution of the project.
Supporting Information
Supporting information for this article is available online at
https://doi.org/10.1055/a-1457-2399. Su
p
p
orti
n
gInformatio
n
Su
p
p
ortingInformatio
n
In conclusion we have developed a simple, efficient, and
reliable catalytic photodehalogenation of aryl bromides un-
der visible-light irradiation with THF both as solvent and as
hydrogen donor. The transformation is distinguished by its
broad applicability to a wide range of aryl halides including
challenging substrate combinations. This protocol has
shown to be particularly useful for promoting dehalogena-
tion events on persistent organic pollutants and for incor-
References and Notes
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POPs/BDEs/Overview/tabid/5371/Default.aspx
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(11) Representative Procedure An oven-dried Schlenk tube con-
taining a stirrer bar was charged with Na2CO3 (0.3 mmol, 31.8
mg, 1.5 equiv) and NiI2 (0.02 mmol, 6.1 mg, 10 mol%). The
Schlenk tube was transferred into a nitrogen-filled glovebox
where dcyb (0.022 mmol, 9.9 mg, 11 mol%), CsI (0.04 mmol,
10.4 mg, 20 mol%) were added. The Schlenk tube was sealed
and removed from the glovebox, 4-bromoanisole (0.2 mmol,
37.4 mg, 1 equiv) and anhydrous THF (0.2 M, 1 mL) was added
using Schlenk line techniques. The mixture was stirred for 15
min. Then, it was placed in a preheated reaction vessel at 35 °C
and stirred for 72 h under blue-light irradiation. The mixture
was quenched with 1 M HCl (2 mL) and extracted with EtOAc,
0.5 cm3 of silica gel were added to the round-bottom flask and
evaporated on a rotary evaporator set at 40 °C and 100 mbar.
The silica was then subjected to column chromatography,
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CDCl3):  = 7.36–7.24 (m, 2 H), 7.01–6.88 (m, 3 H), 3.82 (s, 3 H).
13C NMR (101 MHz, CDCl3):  = 159.5, 129.4, 120.6, 113.9, 55.1.
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© 2021. Thieme. All rights reserved. Synlett 2021, 32, A–D