Amination of Aryl Halides Mediated by Electrogenerated Nickel from Sacrificial Anode

Article abstract of DOI:10.1002/ejoc.202100194

Electrochemical C(sp²)?N couplings mediated by nickel salts generated from the sacrificial anode has been described for the first time. In this approach, the sacrificial nickel anode is employed as the sole source of nickel and the process, operationally simple to set up, enables the preparation of functionalized arylamine derivatives with moderate to good yields, under mild reaction conditions and without additional ligand. A cooperative process between the two electrodes is involved in the proposed mechanism.

Full text of DOI:10.1002/ejoc.202100194

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Very Important Paper
Amination of Aryl Halides Mediated by Electrogenerated
Nickel from Sacrificial Anode
[a]
[a]
[a]
Farah Daili, Stéphane Sengmany,* and Eric Léonel*
2
Electrochemical C(sp )À N couplings mediated by nickel salts
generated from the sacrificial anode has been described for the
first time. In this approach, the sacrificial nickel anode is
employed as the sole source of nickel and the process,
operationally simple to set up, enables the preparation of
functionalized arylamine derivatives with moderate to good
yields, under mild reaction conditions and without additional
ligand. A cooperative process between the two electrodes is
involved in the proposed mechanism.
Introduction
precatalyst. However, it can be pointed out that no example of
aryl halides substrates bearing electron-donating groups has
been described.
Transition metal-catalyzed amination of aromatic and hetero-
[
1]
[14]
aromatic compounds represents a useful transformation in
organic synthesis that enables the synthesis of an aniline moiety
as a common structure found in many biologically active
More recently, Semenov and coll. achieved nickel-cata-
lyzed electrochemical amination of aryl bromides using un-
common alternating current electrolysis. The couplings were
carried out under similar Baran’s experimental conditions with
glassy carbon rod electrodes in an undivided cell (Scheme 1b).
[2]
compounds. Among transition-metal catalysts, nickel is widely
employed mainly due to its low cost compared to palladium
and the potential high reactivity of Ni(0) species towards less
[
15]
Revisited in the mid 80’s, the sacrificial anode process has
been employed in organic synthesis. Since, this method has
been developed for instance in electrogenerated base forma-
[
3]
reactive aromatic halides or pseudo-halides electrophiles.
2
[4]
Traditional nickel-catalyzed chemical C(sp )À N cross-couplings
[
16]
[17]
require the addition of external alkoxide base, elevated temper-
tion
dimerization,
for
subsequent
carbon-carbon,
reactions,
carboxylation,
[
5]
[18]
[19]
[20]
ature, except the rare examples at room temperature, and
long reaction times. Moreover, to avoid glovebox handling,
more and more moisture and air-stable nickel precatalysts such
carbon-silicon,
carbon-
[21]
[22]
boron and carbon-phosphorus cross-couplings. However,
to the best of our knowledge, C(sp )À N bond formation has
2
[6]
[7]
2
as (dppf)Ni[P(OPh) ] ,
(dppf)Ni[o-tolyl]Cl,
(BINAP)Ni(η -
never been previously reported through this electrochemical
process. We describe herein a convenient electrochemical
approach for amination of aryl and heteroaryl halides mediated
by nickel and highlight the capacity of the generated nickel
from the sacrificial anode rod to catalyze the reaction under
constant current electrolysis (CCE), at room temperature and
without additional base or ligand (Scheme 1c).
3
4
[8]
[9]
[10]
NCÀ Ph), NiCl (PPh ) or Ni(bpy) Br
have been reported,
2
3 2
3
2
2
allowing to achieve successfully C(sp )À N bond formation
reactions. Generally, most of them, not commercially available,
need their preparation and require external addition of
reductants to generate catalytically active Ni(0) species. As an
alternative to organic or inorganic reductants, electrochemistry
has been employed to generate the active Ni(0) species from
[
11]
Ni(II) precatalysts. Electrons constitute undoubtedly an ad-
vantage to be inexpensive and inherently safe reagent. In
[
12]
[13]
2
017, Baran et al.
were the first group to investigate on
electrochemical nickel-catalyzed amination of aryl and hetero-
aryl halides (Scheme 1a). The cross-couplings were performed
in an undivided cell using RVC-anode and Ni-cathode under
constant current electrolysis. Contrary to most classical chemical
methods, couplings have been successfully carried out at room
temperature, employing commercially available nickel complex
[
a] F. Daili, Dr. S. Sengmany, Prof. E. Léonel
Electrosynthèse, Catalyse et Chimie Organique
Université Paris-Est Créteil, CNRS, ICMPE, UMR 7182
2
rue Henri Dunant, 94320 Thiais, France
E-mail: sengmany@icmpe.cnrs.fr
leonel@icmpe.cnrs.fr
https://www.icmpe.cnrs.fr/annuaire/sengmany-stephane/
https://www.icmpe.cnrs.fr/annuaire/leonel-eric/
Scheme 1. Nickel-catalyzed electrochemical amination of (hetero)aryl hal-
ides.
Supporting information for this article is available on the WWW under
https://doi.org/10.1002/ejoc.202100194
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Results and Discussion
of 5 mol% of ligand such as 2,2’-bipyridine (entry 12) or 1,10-
phenanthroline (entry 13) did not enable to improve the yield.
In another experiment, the electric current was turned off after
1.75 h electrolysis, then the reaction mixture was continued to
be stirred for 17 h (entry 14). 45% of the coupling-product was
formed but the reaction does not go further in the absence of
electricity. This result proves that the cross-coupling involves
only electrochemical processes. Finally, the replacement of Ni
sacrificial by carbon graphite anode, in the presence of 5% of
At the outset of the study, experimental parameters such as
anode, solvent, nickel catalyst, ligand, current intensity, and the
amount of amine have been examined from 4-bromobenzotri-
fluoride and morpholine as benchmark substrates. It is note-
worthy that morpholine is added in excess as the coupling
partner and as the base. The results are summarized in Table 1.
When performing the coupling reaction using Fe/Ni (64/36)
alloy sacrificial anode in DMF in the presence of 5 mol% of
NiBr bpy precatalyst, did not either improve the yield (entry 15),
2
NiBr bpy precatalyst at a constant current of 0.1 A, the yield of
the expected coupling product does not exceed 10%, hydro-
debromination product was mainly observed (entry 1).
The replacement of Fe/Ni by a pure Ni anode (entry 2) gives
rise to 60% of the isolated product. Surprisingly, the coupling
can be performed without the addition of nickel precatalyst.
Indeed, the product yield was even improved to 74% by
indicating that the efficiency of the cross-coupling requires
freshly in situ generated nickel species.
2
Moreover, to ascertain whether the amount of the amine
can be lowered, attempts were performed with 1.5 or 2
equivalents of morpholine, under the conditions employed in
entry 9. Only moderate yields of the expected product were
obtained, 20 or 43%, respectively. Interestingly, the product can
be maintained in satisfactory yield (61%) with 1.5 equivalent of
morpholine by adding 2 equivalents of triethylamine as an
external base (Scheme 2).
removing NiBr bpy (entry 3), making the procedure even
2
simpler. For the first time, this result shows that nickel
generated from the sacrificial anode is sufficiently efficient to
catalyze the coupling. It is important to note that no reaction
occurs without an electric current (entry 4). The variation of the
current intensity (entries 5 and 6) results in a slight drop of the
yield, especially at a higher current intensity where dimer of
aryl is observed more importantly. Solvents were then exam-
ined (entries 7–11). The yield not only decreases when DMF is
substituted by acetonitrile as a less toxic solvent (entry 7), but
also the reaction is longer (4.5 h instead of 3.5 h). However,
adjusting DMF to 20% in acetonitrile (entry 9) allowed us to
isolate the cross-coupling product with 79% yield. It can be
mentioned that the addition of pyridine as co-solvent (entry 11)
seems to hamper the coupling as less than 10% of the product
was formed, mainly due to the anode passivation. The addition
With these identified experimental conditions in hand, the
scope of (hetero)aryl halides was then investigated. Results are
collected in Table 2.
The electrochemical CÀ N cross-coupling process has over-
all shown good functional group tolerance on the phenyl
ring, except when the substituent is in ortho-position, where
traces of the corresponding coupling product is observed,
probably due to steric effect (compounds 1a”, 1 d”, 1e”).
Good yields were obtained with electron-withdrawing sub-
stituents (trifluoromethyl: 1a, 1 a’, ester: 1b, oxo: 1c, cyano:
1d’). In this series, the nature of halide has also been studied
(compound 1a). It can be noted that aryl bromide gave the
best result compared to iodide or chloride analog. In this
latter, the coupling proceeds much slower. When the
substituent is a halogen atom (fluorine: 1 e, 1e’, chlorine: 1f’,
bromine: 1g, 1 g’), good yields were obtained with fluorine
and chlorine substituent. The yield drops to 26 and 28% with
bromine atom in para- (compound 1g) and meta-position
Table 1. Optimization of experimental conditions.
(
compound 1 g’) respectively, despite the addition of 10
equivalents of morpholine. The limited yields can be
attributed to the formation of side-products such as the
mono-hydro-debromination coupling product, as well as to
the mono-hydro-debromination substrate. Only traces of the
double CÀ N coupling product were observed, probably due
to the presence of amino substituent on phenyl ring which
modifies the reactivity of the second CÀ Br bond involved in
[
a]
Entry
Solvent
Cat or ligand
i (A)
Yield [%]
[
b]
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
DMF
DMF
DMF
DMF
DMF
DMF
MeCN
MeCN/DMF (9/1)
MeCN/DMF (8/2)
MeCN/DMF (7/3)
MeCN/py (9/1)
MeCN/DMF (8/2)
MeCN/DMF (8/2)
MeCN/DMF (8/2)
MeCN/DMF (8/2)
NiBr
NiBr
–
2
2
bpy
bpy
0.10
0.10
0.10
0
<10
60
74
n.r.
70
50
58
61
79
70
–
–
–
–
–
–
–
–
0.08
0.15
0.10
0.10
0.10
0.10
0.10
0.10
0.10
0.10
0.10
[
22c]
the coupling. As previously observed,
halogen substituent
is compatible with the electrochemical coupling process. The
selectivity at one CÀ Br bond offers the possibility for a further
1
1
1
1
1
1
<10
65
bpy
phen
-
75[
c]
45[
d]
NiBr
2
bpy
28
[a] Isolated yield. [b] Using Fe/Ni (64/36) sacrificial anode instead of Ni. [c]
Reaction was electrolyzed for 1.75 h, then the current stopped and the
solution stirred at room temperature for 17 h. [d] Using carbon graphite
anode instead of Ni.
Scheme 2. Reduction of the amine amount.
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[a]
sponding coupling product was obtained with 32% yield
compound 1k). However, coupling of 4-bromo-N,N-dimeth-
Table 2. Scope of (hetero)aryl halides.
(
ylaniline with morpholine failed, traces of the coupling
product was observed at the expense of hydro-debromina-
tion side-product. In the naphthalene and heteroaromatic
halides series, experimental conditions need to be adjusted.
Indeed, with naphthalene bromides derivatives, the increase
of the amount of morpholine from 3 to 5 equivalents allowed
to afford the expected products, albeit with limited yields
(
compounds 1m, 1m’ and 1n).
In the case of heteroaromatic bromides, by increasing
morpholine to 10 equivalents and by lowering the constant
current intensity to 50 mA, 55 and 33% yields of the coupling
products were isolated from 3-bromopyridine (compound 1o)
and 3,5-dibromopyridine (compound 1p), respectively. Finally,
with 3-bromothiophene, 30% isolated yield of the expected
product (compound 1q) was obtained when 5 equivalents of
morpholine are used at a constant current of 50 mA.
The scope of the cyclic amines was then explored
(
Table 3) by maintaining 4-bromobenzotrifluoride as the aryl
bromide model and the optimized experimental conditions
found in entry 9 of Table 1. In this study, it must be
emphasized that the amount of the amine was increased
from 3 to 5 equivalents as the yield of the coupling product
in the case of pyrrolidine was significantly improved from 27
to 53 % (compound 2b), while reaction time reduced.
Couplings can be achieved successfully with moderate to
good yields, except for 1-phenylpiperazine (compound 2d).
Unlike tetrahydroisoquinoline (compound 2g), indoline,
which is less nucleophilic, led mainly to hydro-debromination
side-product (compound 2h).
Additionally, attempts of coupling with secondary acyclic
amines such as diethylamine and dipropylamine or with
primary amines such as cyclohexylamine and benzylamine have
led to the cross-coupling product in minor amount.
[
a]
Table 3. Scope of cyclic amines.
[
a] Reaction conditions: undivided cell, nickel anode, nickel cathode,
tetraethylammonium tetrafluoroborate (0.7 mmol), acetonitrile/DMF (80/
20), (hetero)aryl bromide (4 mmol), amine (12 mmol), constant current:
0.1 A, room temperature. [b] With 10 equiv. of morpholine. [c] Addition of
5 mol% of 1,10-phenanthroline. [d] With 5 equiv. of morpholine. [e] With
10 equiv. of morpholine at 50 mA. [f] With 5 equiv. of morpholine at
50 mA.
coupling. Without substituent, 58% yield was isolated from
bromobenzene (compound 1h).
Moderate yields were achieved with electron-donating
substituents (methoxy: 1i, 1i’, methyl: 1j, 1j’). In this series of
substituents, aryl iodides gave generally better results than
aryl bromides. It is noteworthy that, in the case of 4-
iodoanisole, the addition of a catalytic amount of 1,10-
phenanthroline as an external ligand is needed to achieve
the coupling with 30% isolated yield. Nevertheless, with aryl
bromide such as 1-bromo-4-tert-butylbenzene, the corre-
[
a] Reaction conditions: undivided cell, nickel anode, nickel cathode,
tetraethylammonium tetrafluoroborate (0.7 mmol), acetonitrile/DMF (80/
20), 4-bromobenzotrifluoride (4 mmol), amine (20 mmol), constant current:
0
.1 A, room temperature. [b] Reaction performed with 3 equiv. of amine.
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In a last experiment, a gram-scale of the electrochemical
followed by the reductive elimination gives rise to the cross-
(
0)
CÀ N coupling between 4-bromobenzotrifluoride and morpho-
line has been performed (Scheme 3). It must be mentioned that
in a larger scale, the process is more efficient at a constant
current of 50 mA (70% isolated yield of the coupling product
vs. 54% at 100 mA.
In order to elucidate the mechanism of the coupling, a
control experiment has been carried out (Scheme 4). When the
reaction was performed in a divided cell under constant current
coupling product and the release of Ni . It is important to
note that the generated nickel is involved in a cooperative
process between the two electrodes, allowing the formation
of nickel intermediates. Nevertheless, at this stage, the
(
I)
(III)
[10]
alternative catalytic cycle through Ni /Ni system
not be completely ruled out.
could
electrolysis in the presence of 10 mol% NiCl , no cross-coupling Conclusion
2
product was observed, showing that a step of oxidation at the
anode is required.
2
In summary, C(sp )À N couplings have been successfully
achieved, mediated by nickel electrogenerated from the anode
rod. This work constitutes, to the best of our knowledge, the
first example of metal salts generated from the electrode, which
enables the cross-couplings to proceed at room temperature
under constant current electrolysis, without additional ligand.
The electrochemical process, practical and operationally simple
to set up, tolerates a good range of functional groups and
allows access to arylamine derivatives with modest to good
yields. The proposed nickel-mediated mechanism relies on a
cooperative process between the two electrodes.
Thus, based on the mechanistic proposal reported previ-
[22c]
[11c]
ously in the C-P
and C–C
bonds formation, as well as from
the experiment in a divided cell and from the optimization
results, the postulated CÀ N cross-coupling mechanism is as
follow (Scheme 5).
[
23]
Nickel catalyst, generated from the sacrificial anode,
enables the oxidative addition to occur with aryl bromide.
(
II)
Single reductive electron transfer of Ni intermediate and its
complexation with the amine leads to the formation of
nickelate species. A further step of oxidation at the anode,
Experimental Section
General Information. Solvents and reagents were purchased
from commercial suppliers and used without further purification.
Melting points (mp) were measured on a Büchi B-545 apparatus.
NMR spectra were recorded in CDCl on a Brucker Avance II 400
3
spectrometer. Chemical shift (δ) are reported in parts per million
(ppm) relative to the residual solvent signal. Coupling constant
values (J) are given in Hertz (Hz) and refer to apparent
multiplicities, indicated as follows: s (singlet), d (doublet), dd
Scheme 3. Gram-scale electrosynthesis.
(
doublet of doublet), dt (doublet of triplet), t (triplet), q (quartet),
+
m (multiplet). Mass spectra (MS in electronic impact (EI )
ionization mode) were measured on a Thermo Scientific ITQ 700
GC-MS spectrometer fitted with Varian column (l=25 m, Ø=
0
.25 mm, df=0.25 μm). High-resolution Mass Spectrometry
+
(
HRMS) spectra were measured in ESI mode by the mass
Scheme 4. Control experiments.
spectrometry service of the “Institut de Chimie Organique et
Analytique”, Orléans (France). Only new compounds are charac-
terized by HRMS analysis. Compounds that have been previously
described in the literature are linked to the corresponding
bibliographic references.
General procedure for preparation of arylamine derivatives
(
see Figures S1-S3 of the Supporting information for the
undivided electrochemical cell device). To a 25 mL undivided
electrochemical cell, fitted by a sacrificial nickel anode (Ø=
1
1
0 mm) surrounded by a nickel foam as the cathode (surface:
5 cm , Nitech, porosity 500 μm) were added acetonitrile
2
(
16 mL), N,N’-dimethylformamide (4 mL), tetraethylammonium
tetrafluoroborate (150 mg, 0.69 mmol) and 1,2-dibromoethane
100 μL, 1.16 mmol). First, the mixture is electrolyzed at a
(
constant current intensity of 0.1 A for 15 minutes at room
temperature. Then the current is stopped and were sequentially
added (hetero)aryl bromide (4 mmol, 1.0 equiv.) and secondary
amine (12 mmol, 3 equiv.). The solution is electrolyzed at 0.1 A
for 3–4 h (GC monitoring). A saturated EDTA aqueous solution
(
30 mL) was added, and the resulting solution is extracted with
AcOEt (3×30 mL). The combined organic layers were washed
with H O (2 ×100 mL) and a saturated NaCl aqueous solution
Scheme 5. Postulated mechanism.
2
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(
100 mL), dried over Na SO , filtered, and evaporated under
113.1, 66.6, 48.5. MS, m/z (relative intensity): 189 (11),188 (77,
*
+
2
4
vacuum. The crude product was purified by flash chromatog-
raphy on silica (granulometry 70–200 μm), eluted with a gradient
mixture of solvents (EP/AcOEt or CH Cl /AcOEt for polar com-
pounds such as piperazine derivatives) to afford the pure
product.
[M] ),187 (17),157 (11),131 (10),130 (79),129(100),102 (36), 75 (11).
[
28]
4
(
6
(
-(4-Fluorophenyl)morpholine (1e).
Reaction time: 4 h. Oil
2
2
1
480 mg, 66%). H NMR (400 MHz, CDCl ): δ 7.00–6.96 (m, 2H), 6.88–
.85 (m, 2H), 3.87–3.85 (m, 4H), 3.09–3.07 (m, 4H). F{ H} NMR
3
1
9
1
13 1
376 MHz, CDCl ): δ À 124.18. C{ H} NMR (100 MHz, CDCl ): δ 157.4
3
3
1
4
3
Procedure for cross-coupling assay in divided cell (see Fig-
ure S4 of the Supporting information for the divided electro-
chemical cell device). To a 20 mL divided electrochemical cell
separated by a sinter, were added in anodic compartment fitted
(d, J =239.2 Hz), 148.0 (d, J =2.3 Hz), 117.5 (d, J =7.6 Hz),
C-F C-F C-F
2
115.6 (d, J =22.1 Hz), 66.9, 50.4. MS, m/z (relative intensity): 182
C-F
*
+
(17),181 (99, [M] ),180 (19),150 (5), 124 (8),123(100),122 (97),109
(5), 95 (36), 75 (17), 74 (8).
by
ylformamide (10 mL), tetraethylammonium tetrafluoroborate
600 mg, 0.28 M). The cathodic compartment, fitted with nickel
foam (15 mm x 55 mm, Nitech, porosity 500 μm), contains N,N’-
dimethylformamide (10 mL), tetraethylammonium tetrafluorobo-
a
sacrificial nickel anode (Ø=10 mm), N,N’-dimeth-
[
28]
4
(
(
(
(
1
2
-(3-Fluorophenyl)morpholine (1e’).
Reaction time: 3.5 h. Oil
1
345 mg, 48%). H NMR (400 MHz, CDCl ): δ 7.24–7.16 (m, 1H), 6.67
d, J=8.3 Hz, 1H), 6.60–6.54 (m, 2H), 3.87–3.85 (m, 4H), 3.17–3.15
3
(
1
9
1
13
1
m, 4H). F{ H} NMR (376 MHz, CDCl ): δ À 112.15. C{ H} NMR
3
1
3
100 MHz, CDCl ): δ 163.9 (d, J =243.4 Hz), 153.0 (d, J =9.8 Hz),
3
C-F
C-F
rate (600 mg, 0.28 M), NiCl (10 mol%), 4-bromobenzotrifluoride
2
3
4
2
30.2 (d, JC-F =9.9 Hz), 110.8 (d, JC-F =2.5 Hz), 106.3 (d, JC-F =
2
(
2 mmol, 1 equiv) and morpholine (6 mmol, 3 equiv). The result-
ing solution is electrolyzed at a constant current intensity of
.05 A at room temperature under stirring for 3 h. The reaction
1.5 Hz), 102.5 (d, JC-F =25.2 Hz), 66.8, 48.9. MS, m/z (relative
*
+
intensity): 182 (21),181(100, [M] ),180 (13),124 (9),123 (52),122 (43),
0
96 (8), 95 (13), 75 (6).
was monitored by GC and no expected cross-coupling was
observed.
[
29]
4
(
-(3-Chlorophenyl)morpholine (1f’).
Reaction time: 3.5 h. Oil
1
600 mg, 76%). H NMR (400 MHz, CDCl ): δ 7.18 (t, J=8.0 Hz, 1H),
3
6
3
.87–6.85 (m, 2H), 6.78 (d, J=8.3 Hz, 1H), 3.86–3.84 (m, 4H), 3.16–
Compounds characterization
13 1
.14 (m, 4H). C{ H} NMR (100 MHz, CDCl ): δ 152.4, 135.1, 130.1,
3
[
24]
119.8, 115.6, 113.6, 66.8, 48.9. MS, m/z (relative intensity): 200 (6),
4
3
-(4-(Trifluoromethyl)phenyl)morpholine (1a).
Reaction time:
*
+
1
199 (36), 198 (20), 197 (100, [M] ), 196 (19), 182 (6), 168 (6), 166
10), 141 (30), 140 (32), 139 (90), 138 (67), 113 (8), 112 (8), 111 (21),
77 (6), 75 (15), 74 (5).
.5 h. White solid (730 mg, 79%). mp 68.2°C. H NMR (400 MHz,
(
CDCl ): δ 7.51–7.49 (m, 2H), 6.92 (d, J=8.6 Hz, 2H), 3.88–3.86 (m,
3
19
1
13
4
H), 3.25–3.23 (m, 4H). F{ H} NMR (376 MHz, CDCl ): δ À 61.40.
C
3
1
3
{
H} NMR (100 MHz, CDCl ): δ 153.4, 126.5 (q, J =3.8 Hz), 124.7 (q,
[30]
3
C-F
4-(4-Bromophenyl)morpholine (1g). Reaction time: 3 h. White
1
2
JC-F =270.7 Hz). 121.0 (q, J =32.7 Hz), 114.4, 66.7, 48.2. MS, m/z
1
C-F
solid (256 mg, 26%). mp 115.0°C. H NMR (400 MHz, CDCl ): δ 7.36
*
+
3
(
(
(
relative intensity): 233 (2), 232 (17),231(100, [M] ),230 (14),229
2),216 (2),213 (2),212 (10),201 (3),200 (7),174 (9),173 (75),172
57),146 (4),145 (18),127 (2),126 (2),125 (3), 95 (3), 75 (3).
(
d, J=8.5 Hz, 2H), 6.78 (d, J=8.4 Hz, 2H), 3.86–3.84 (m, 4H), 3.12 (t,
J=4.8 Hz, 4H). C{ H} NMR (100 MHz, CDCl ): δ 150.3, 132.0, 117.3,
13 1
3
1
12.2, 66.8, 49.2. MS, m/z (relative intensity): 244 (11), 243 (87), 242
*
+
[
25]
(23, [M] ), 241 (89), 240 (14), 212 (6), 210 (5), 186 (8), 185 (92), 184
(50), 183 (100), 182 (43), 157 (8), 155 (9), 77 (6), 76 (5), 75 (6).
4
3
8
-(3-(Trifluoromethyl)phenyl)morpholine (1a’).
Reaction time:
1
.5 h. Oil (680 mg, 74%). H NMR (400 MHz, CDCl ): δ 7.37 (t, J=
.2 Hz, 1H), 7.11 (d, J=6.3 Hz, 2H), 7.06 (dd, J=8.3, 2.5 Hz, 1H), 3.88
t, J=4.9 Hz, 4H), 3.27–3.15 (m, 4H). F{ H} NMR (376 MHz, CDCl ): δ
3
[31]
4
-(3-Bromophenyl)morpholine (1 g’).
Reaction time: 3 h. Oil
19
1
(
1
3
(273 mg, 28%). H NMR (400 MHz, CDCl ): δ 7.12 (t, J=8.1 Hz, 1H),
3
13
1
2
À 62.74. C{ H} NMR (100 MHz, CDCl ): δ 151.4, 131.5 (q, JC-F
=
=
3
7.02–6.96 (m, 2H), 6.82 (d, J=8.3 Hz, 1H), 3.86–3.84 (m, 4H), 3.16–
1
3
3
3
1.7 Hz), 129.6, 124.3 (q, JC-F =272.5 Hz), 118.5, 116.3 (q, JC-F
13
1
3.14 (m, 4H).
C{ H} NMR (100 MHz, CDCl ): δ 152.5, 130.4, 123.3,
3
3
.9 Hz), 112.0 (q, JC-F =3.9 Hz), 66.8, 48.9. MS, m/z (relative
intensity): 233 (2),232 (21),231(100, [M] ),230 (16),216 (1),212
6),202 (1),201 (3),200 (7),174 (8),173 (79),172 (69),159 (1),146 (4),145
24),127 (3),125 (3), 95 (3), 75 (3), 57 (2).
122.7, 118.5, 114.1, 66.8, 48.9. MS, m/z (relative intensity): 244 (10),
*
+
*
+
2
43 (87), 242 (23, [M] ), 240 (14), 226 (6), 212 (9), 210 (9), 186 (9),
(
(
185 (88), 184 (44), 183 (100), 182 (38), 157 (8), 155 (9), 77 (9), 51 (6).
[
24]
4
(
-Phenylmorpholine (1h).
Reaction time: 4 h. White solid
[
26]
Ethyl 4-morpholinobenzoate (1b).
Reaction time: 3.5 h.
1
380 mg, 58%). mp 52.0°C. H NMR (400 MHz, CDCl ): δ 7.27 (t, J=
3
1
Yellow solid (660 mg, 70%). mp 85.0°C. H NMR (400 MHz,
7
.4 Hz, 2H), 6.91 – 6.86 (m, 3H), 3.85–3.83 (m, 4H), 3.13–3.11 (m, 4H).
CDCl ): δ 7.94 (d, J= 8.2 Hz, 2H), 6.86 (d, J=8.5 Hz, 2H), 4.33 (d,
13
1
3
C{ H} NMR (100 MHz, CDCl ): δ 151.4, 129.3, 120.2, 115.8, 67.0,
3
*
+
J= 7.1 Hz, 2H), 3.86–3.84 (m, 4H), 3.29–3.26 (m, 4H), 1.37 (t, J=
4
9.4. MS, m/z (relative intensity): 164 (16), 163 (100, [M] ), 162 (24),
1
3
1
7
1
2
(
(
.1 Hz, 3H). C{ H} NMR (100 MHz, CDCl ): δ 166.6, 154.2, 131.2,
20.7, 113.5, 66.7, 60.4, 47.8, 14.4. MS, m/z (relative intensity):
36 (16),235(100, [M] ),234 (14),207 (8),206 (5),204 (4),190
16),178 (6),177 (37),176 (12),150 (5),149 (45),148 (10),133 (5),132
32),118 (3),104 (6), 78 (5), 77 (5), 51 (3).
3
133 (6), 132 (21), 106 (10), 105 (84), 104 (98), 91 (6), 78 (8), 77 (62),
51 (15).
*
+
[
24]
4
-(4-Methoxyphenyl)morpholine (1i). Reaction time: 4 h. Brown
1
solid (230 mg, 30%). mp 73.1°C. H NMR (400 MHz, CDCl ): δ 6.89
3
(
3
d, J=9.0 Hz, 2H), 6.85 (d, J=9.3 Hz, 2H), 3.87–3.85 (m, 4H), 3.77 (s,
[
27]
1
-(4-Morpholinophenyl)ethanone (1c).
Reaction time: 3.5 h.
13
1
H), 3.07–3.04 (m, 4H). C{ H} NMR (100 MHz, CDCl ): δ 154.0, 145.7,
3
1
Yellow solid (550 mg, 67%). mp 93.8°C. H NMR (400 MHz, CDCl ): δ
3
117.9, 114.5, 67.1, 55.6, 50.9. MS, m/z (relative intensity): 194 (15),
*
+
7
3
1
.88 (d, J=8.9 Hz, 2H), 6.86 (d, J=8.7 Hz, 2H), 3.86–3.84 (m, 4H),
193 (100, [M] ), 192 (7), 178 (42), 136 (7), 135 (61), 134 (12), 121
13
1
.31–3.29 (m, 4H), 2.52 (s, 3H). C{ H} NMR (100 MHz, CDCl ): δ
3
(10), 120 (62), 92 (11), 77 (6), 65 (8).
96.6, 154.3, 130.4, 128.2, 113.3, 66.6, 47.6, 26.2. MS, m/z (relative
intensity): 206 (15),205(100, [M] ),204 (7),191 (11),190 (80),147
12),133 (11),132 (97),104 (12), 91 (6), 78 (11), 77 (8), 51 (6).
*
+
[25]
4
(
-(3-Methoxyphenyl)morpholine (1i’).
Reaction time: 4 h. Oil
1
430 mg, 56%). H NMR (400 MHz, CDCl ): δ 7.25 (t, J=8.1 Hz, 1H),
(
3
6
3
.58 (d, J=8.3 Hz, 1H), 6.51 (d, J=9.4 Hz, 2H), 3.90–3.88 (m, 4H),
[
28]
3
-Morpholinobenzonitrile (1d’). Reaction time: 3 h. Yellow solid
13 1
.83 (s, 3H), 3.19–3.17 (m, 4H). C{ H} NMR (100 MHz, CDCl ): δ
3
1
(
(
{
380 mg, 51%). mp 101.8°C. H NMR (400 MHz, CDCl ): δ 7.35–7.31
3
160.7, 152.8, 129.9, 108.6, 104.8, 102.3, 66.9, 55.2, 49.3. MS, m/z
1
3
*
m, 1H), 7.12–7.09 (m, 3H), 3.87–3.84 (m, 4H), 3.18–3.16 (m, 4H).
C
+
(relative intensity): 194 (14), 193 (100, [M] ), 192 (16), 178 (33), 162
1
H} NMR (100 MHz, CDCl ): δ 151.4, 130.0, 123.0, 119.6, 119.3, 118.2,
3
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doi.org/10.1002/ejoc.202100194
*
+
(
7
11), 136 (9), 135 (68), 134 (18), 108 (19), 107 (10), 106 (8), 104 (6),
9 (10), 78 (27), 77 (17).
(27, [M] ), 242 (100), 241 (16), 229 (4), 213 (7), 212 (4), 211 (6), 187
(7), 186 (76), 185 (32), 184 (80), 183 (25), 158 (7), 156 (7), 105 (5), 78
(
6), 76 (7), 51 (6).
[
32]
4
-(4-Methylphenyl)morpholine (1j). Reaction time: 4 h. Yellow
1
[35]
solid (300 mg, 42%). mp 41.9°C. H NMR (400 MHz, CDCl ): δ 7.10
4-(Thiophen-3-yl)morpholine (1q). Reaction time: 21 h. Brown
3
1
(
3
1
(
d, J=8.2 Hz, 2H), 6.85 (d, J=8.3 Hz, 2H), 3.88–3.86 (m, 4H), 3.13–
solid (203 mg, 30%). mp 87.1°C. H NMR (400 MHz, CDCl ): δ 7.27-
3
13
1
.11 (m, 4H), 2.29 (s, 3H). C{ H} NMR (100 MHz, CDCl ): δ 149.2,
7.24 (m, 1H), 6.86 (dt, J=5.3, 1.6 Hz, 1H), 6.21–6.20 (m, 1H), 3.86–
3
1
3
1
29.7, 129.6, 116.1, 67.0, 50.0, 20.5. MS, m/z (relative intensity): 178
15), 177 (100, [M] ), 176 (17), 162 (3), 146 (7), 133 (3), 132 (8), 130
3), 120 (8), 119 (79), 118 (41), 117 (5), 92 (7), 91 (82), 90 (3), 89 (5),
3.83 (m, 4H), 3.09 (td, J=4.7, 1.7 Hz, 4H). C{ H} NMR (100 MHz,
*
+
CDCl ): δ 152.4, 125.6, 119.6, 100.5, 66.7, 50.8. MS, m/z (relative
intensity): 171 (5), 170 (13), 169 (100, [M] ), 168 (9), 167 (4), 156 (3),
155 (6), 154 (63), 140 (8), 138 (6), 126 (4), 113 (4), 112 (10), 111 (68),
3
*
+
(
7
7 (5), 65 (11), 63 (3), 51 (2).
1
10 (74), 97 (5), 85 (3), 84 (18), 83 (6), 58 (6).
[
24]
4
(
-(3-Methylphenyl)morpholine (1j’).
Reaction time: 4 h. Oil
1
[24]
380 mg, 54%). H NMR (400 MHz, CDCl ): δ 7.24 (t, J=7.7 Hz, 1H),
.81–6.78 (m, 3H), 3.93–3.91 (m, 4H), 3.21–3.19 (m, 4H), 2.40 (s, 3H).
C{ H} NMR (100 MHz, CDCl ): δ 151.4, 138.9, 129.1, 121.1, 116.7,
13.0, 67.0, 49.6, 21.9. MS, m/z (relative intensity): 178 (14), 177
1-(4-(Trifluoromethyl)phenyl)pyrrolidine (2b). Reaction time: 2.5 h.
3
1
6
White solid (455 mg, 53%). mp 94.0°C. H NMR (400 MHz, CDCl ): δ
3
13
1
7.47 (d, J=8.4 Hz, 2H), 6.57 (d, J=8.4 Hz, 2H), 3.33 (d, J=6.1 Hz, 4H),
3
19
1
1
2.05 (dt, J=4.4, 2.8 Hz, 4H). F{ H} NMR (376 MHz, CDCl ): δ À 60.51.
3
*
+
13
1
3
(
1
100, [M] ), 176 (20), 162 (6), 146 (10), 132 (14), 120 (8), 119 (75),
C{ H} NMR (100 MHz, CDCl ): δ 149.8, 126.4 (q, J =3.8 Hz), 125.5 (q,
3 C-F
2
1
18 (62), 92 (8), 91 (57), 65 (11).
JC-F =269.9 Hz), 116.6 (q, JC-F =32.5 Hz), 110.9, 47.5, 25.5. MS, m/z
*
+
(
1
relative intensity): 216 (13), 215 (64, [M] ), 214 (100), 196 (7), 172 (14),
59 (17), 145 (12).
[
32]
4
-(4-(Tert-butyl)phenyl)morpholine (1k).
Reaction time: 4 h.
1
White solid (282 mg, 32%). mp 96.0°C. H NMR (400 MHz, CDCl ): δ
3
[
36]
7
3
1
.32 (d, J=8.1 Hz, 2H), 6.88 (d, J=8.2 Hz, 2H), 3.88–3.86 (m, 4H),
1-Methyl-4-(4-(trifluoromethyl)phenyl)piperazine (2c). Reaction
13
1
1
.16–3.14 (m, 4H), 1.31 (s, 9H). C{ H} NMR (100 MHz, CDCl ): δ
time: 3 h. Yellow solid (454 mg, 46%). mp 88.6°C. H NMR
3
48.9, 142.9, 126.0, 115.5, 67.0, 49.6, 34.0, 31.5. MS, m/z (relative
(400 MHz, CDCl ): δ 7.48 (d, J=8.5 Hz, 2H), 6.93 (d, J=8.5 Hz, 2H),
3
.
+
19
1
intensity): 220 (5, [M+H] ), 219 (32), 205 (15), 204 (100), 202 (2),
89 (3), 160 (5), 159 (4), 158 (2), 146 (9), 145 (3), 144 (2), 132 (3), 131
4), 130 (4), 118 (5), 117 (4), 115 (2), 91 (3), 77 (3).
3.32–3.29 (m, 4H), 2.59-2.56 (m, 4H), 2.36 (s, 3H). F{ H} NMR
13 1
1
(
(376 MHz, CDCl ): δ À 61.35. C{ H} NMR (100 MHz, CDCl ): δ 153.3,
3 1 2
3
3
126.4 (q, J =3.8 Hz), 124.8 (q, JC-F =270.7 Hz), 120.4 (q, JC-F =
C-F
3
2
2.8 Hz), 114.5, 54.8, 47.9, 46.1. MS, m/z (relative intensity): 245 (14),
44 (100, [M] ), 243 (16), 229 (16), 225 (14), 202 (14), 201 (10), 200
[
24]
4
-(Naphthalen-1-yl)morpholine (1m). Reaction time: 3 h. Brown
*
+
1
solid (255 mg, 30%). mp 83.3°C. H NMR (400 MHz, CDCl ): δ 8.24
3
(17), 174 (7), 173 (27), 172 (34), 159 (6), 145 (19), 70 (10).
(
d, J=7.9 Hz, 1H), 7.84 (d, J=7.5 Hz, 1H), 7.59 (d, J=8.1 Hz, 1H),
[36]
7
4
1
(
(
(
.54–7.45 (m, 2H), 7.45–7.37 (m, 1H), 7.12 (d, J=6.8 Hz, 1H), 4.01 (s,
1-Phenyl-4-(4-(trifluoromethyl)phenyl)piperazine (2d). Reaction
13
1
1
H), 3.14 (s, 4H). C{ H} NMR (100 MHz, CDCl ): δ 134.8, 128.7, 128.5,
26.5, 126.0, 125.9, 125.6, 124.1, 123.4, 114.8, 67.4, 53.6. MS, m/z
relative intensity): 214 (16), 213 (100, [M] ), 212 (22), 211 (3), 198
4), 183 (3), 182 (6), 168 (4), 167 (5), 156 (6), 155 (47), 154 (78), 153
2), 141 (4), 128 (8), 127 (22), 126 (6), 115 (4), 77 (3), 75 (3).
time: 4 h. Brown solid (215 mg, 18%). mp 63.7°C. H NMR (400 MHz,
3
CDCl ): δ 7.53 (d, J=8.4 Hz, 2H), 7.33 (t, J=7.7 Hz, 2H), 7.03–6.95
3
*
+
19
1
(m, 5H), 3.46 (t, J=4.7 Hz, 4H), 3.36 (t, J=4.7 Hz, 4H). F{ H} NMR
13 1
(376 MHz, CDCl ): δ À 61.29. C{ H} NMR (100 MHz, CDCl ): δ 153.2,
3
3
3
1
150.9, 129.3, 126.5 (q, J =3.8 Hz), 124.8 (q, J =270.7 Hz), 120.9
C-F
C-F
2
(q, J =11.9 Hz), 120.6, 116.6, 114.8, 49.4, 48.1. MS, m/z (relative
C-F
*
+
[
24]
4
-(Naphthalen-2-yl)morpholine (1 m’). Reaction time: 3 h. Pink
intensity): 307 (21), 306 (100, [M] ), 305 (8), 291 (16), 287 (7), 264
14), 201 (5), 200 (26), 173 (27), 172 (28), 145 (13), 132 (22), 106 (6),
05 (20), 104 (27), 91 (6), 77 (13).
1
solid (293 mg, 34%). mp 84.0°C. H NMR (400 MHz, CDCl ): δ 7.76–
3
(
1
7
(
.69 (m, 3H), 7.42 (t, J=7.5 Hz, 1H), 7.31 (t, J=7.4 Hz, 1H), 7.29–7.24
13 1
m, 1H), 7.13 (s, 1H), 3.94–3.91 (m, 4H), 3.28–3.26 (m, 4H). C{ H}
NMR (100 MHz, CDCl ): δ 149.1, 134.6, 128.9, 128.7, 127.5, 126.8,
1-Benzyl-4-(4-(trifluoromethyl)phenyl)piperazine (2e). Reaction
3
1
1
26.4, 123.6, 119.0, 110.2, 67.0, 49.9. MS, m/z (relative intensity): 214
time: 3.5 h. Yellow solid (507 mg, 40%). mp 85.0°C. H NMR
*
+
(16), 213 (100, [M] ), 212 (10), 198 (17), 182 (7), 156 (12), 155 (81),
(400 MHz, CDCl ): δ 7.47 (d, J=8.5 Hz, 2H), 7.42–7.23 (m, 5H), 6.91
3
154 (25), 128 (20), 127 (20), 126 (6).
(d, J=8.5 Hz, 2H), 3.58 (d, J=1.4 Hz, 2H), 3.30– 3.27 (m, 4H), 2.63–
1
9
1
13
1
2
(
3
6
.60 (m, 4H). F{ H} NMR (376 MHz, CDCl ): δ À 61.30. C{ H} NMR
[
33]
3
4
3
-(6-Methoxynaphthalen-2-yl)morpholine (1n).
Reaction time:
3
100 MHz, CDCl ): δ 153.4, 137.7, 129.3, 128.4, 127.3, 126.4 (q, J
.8 Hz), 124.8 (q, JC-F =270.5 Hz), 120.4 (q, JC-F =32.7 Hz), 114.5,
3.0, 52.8, 48.0. MS, m/z (relative intensity): 321 (22), 320 (100,
=
1
3
C-F
h. Pink solid (260 mg, 27%). mp 150.0°C. H NMR (400 MHz,
1
2
CDCl ): δ 7.64 (dd, J=17.1, 8.9 Hz, 2H), 7.23 (s, 1H), 7.11–7.07 (m,
3
1
3
1
3
H), 3.96–3.89 (m, 4H), 3.23 (t, J=4.7 Hz, 4H), 1.57 (s, 3H). C{ H}
*
+
[
M] ), 319 (10), 301 (15), 292 (6), 229 (11), 202 (15), 200 (8), 189 (6),
NMR (100 MHz, CDCl ): δ 156.2, 147.7, 129.8, 129.6, 128.4, 127.7,
3
1
74 (11), 173 (9), 172 (18), 146 (16), 145 (16), 132 (6), 119 (32), 118
1
19.7, 119.0, 110.8, 105.8, 67.0, 55.3, 50.3. MS, m/z (relative
+
*
+
(48), 91 (34), 65 (7). HRMS (ESI ) m/z calcd for C18H F N [M+H],
20 3 2
intensity): 244 (17), 243 (100, [M] ), 242 (5), 229 (5), 228 (32), 186
321.1573; found, 321.1571.
(11), 185 (69), 171 (8), 170 (34), 142 (17), 115 (8).
[
37]
1
2
8
-(4-(Trifluoromethyl)phenyl)piperidine (2f).
Reaction time:
[
24]
4
5
7
-(Pyridin-3-yl)morpholine (1o). Reaction time: 5 h. Oil (360 mg,
1
.5 h. Oil (566 mg, 62%). H NMR (400 MHz, CDCl ): δ 7.45 (d, J=
.5 Hz, 2H), 6.91 (d, J=8.5 Hz, 2H), 3.27 (t, J=5.2 Hz, 4H), 1.66 (dt,
1
3
5%). H NMR (400 MHz, CDCl ): δ 8.29 (s, 1H), 8.12–8.10 (m, 1H),
.17–7.15 (m, 2H), 3.87-3.85 (m, 4H), 3.18-3.16 (m, 4H). C{ H} NMR
3
13
1
19
1
13
1
J=23.6, 5.2 Hz, 6H). F{ H} NMR (376 MHz, CDCl ): δ À 61.14. C{ H}
3
(
100 MHz, CDCl ): δ 146.9, 141.1, 138.3, 123.5, 122.1, 66.7, 48.6. MS,
3
1
3
*
+
NMR (100 MHz, CDCl ): δ 153.8, 126.3 (q, JC-F =3.8 Hz), 124.9 (q, JC-
3
2
m/z (relative intensity): 165 (9), 164 (100, [M] ), 163 (25), 162 (4),
49 (2), 135 (2), 134 (4), 133 (10), 119 (3), 107 (11), 106 (81), 105
66), 92 (2), 80 (2), 79 (7), 78 (35), 65 (2), 52 (5), 51 (13), 50 (3).
=270.5 Hz), 119.5 (q, J =32.6 Hz), 114.6, 49.3, 25.4, 24.3. MS, m/z
C-F
*
+
F
1
(
(relative intensity): 230 (9), 229 (57, [M] ), 228 (100), 210 (7), 200
(13), 188 (8), 173 (12), 172 (22), 145 (12).
[
34]
4
-(5-Bromopyridin-3-yl)morpholine (1p).
Reaction time: 4.5 h.
2-(4-(Trifluoromethyl)phenyl)-1,2,3,4-tetrahydroiso
quinoline
1
[38]
Pink solid (325 mg, 33%). mp 82.2°C. H NMR (400 MHz, CDCl ): δ
(2g). Reaction time: 2.5 h. White solid (448 mg, 43%). mp 82.7°C.
3
1
8
4
1
.17 (s, 1H), 8.12 (s, 1H), 7.26 (s, 1H), 3.84–3.82 (m, 4H), 3.18–3.16 (m,
H NMR (400 MHz, CDCl ): δ 7.51 (d, J=8.5 Hz, 2H), 7.24-7.18 (m,
3
13
1
H). C{ H} NMR (100 MHz, CDCl ): δ 147.8, 141.3, 136.1, 124.2,
4H), 6.94 (d, J=8.5 Hz, 2H), 4.49 (s, 2H), 3.64 (t, J=5.6 Hz, 2H), 3.00
3
1
9
1
13
1
20.9, 66.5, 48.1. MS, m/z (relative intensity): 245 (11), 244 (93), 243
(t, J=5.9 Hz, 2H). F{ H} NMR (376 MHz, CDCl ): δ À 61.02. C{ H}
3
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© 2021 Wiley-VCH GmbH

Full Papers
doi.org/10.1002/ejoc.202100194
NMR (100 MHz, CDCl ): δ 152.1, 134.9, 133.8, 128.4, 126.7, 126.5,
C. Thobie-Gautier, M. Pipelier, J. Lebreton, D. Dubreuil, J. Org. Chem.
013, 78, 370–379; d) D. Liu, H.-X. Ma, P. Fang, T.-S. Mei, Angew. Chem.
Int. Ed. 2019, 58, 5033–5037; Angew. Chem. 2019, 131, 5087–5091; e) Y.
Bai, N. Liu, S. Wang, S. Wang, S. Ning, L. Shi, L. Cui, Z. Zhang, J. Xiang,
Org. Lett. 2019, 21, 6835–6838; f) See also reference [9]; g) For a review,
see: P. Gandeepan, L. H. Finger, T. H. Meyer, L. Ackermann, Chem. Soc.
Rev. 2020, 49, 4254–4272.
3
1
2
2
1
1
26.5, 126.4, 125.0 (q, JC-F =270.4 Hz), 119.0 (q, JC-F =32.5 Hz),
13.0, 49.4, 45.2, 29.0. MS, m/z (relative intensity): 278 (12), 277 (75,
*
+
[M] ), 276 (100), 274 (6), 258 (6), 115 (6), 104 (13), 103 (6), 78 (13).
[
12] E. J. Horn, B. R. Rosen, P. S. Baran, ACS Cent. Sci. 2016, 2, 302–308.
Acknowledgements
[13] a) C. Li, Y. Kawamata, H. Nakamura, J. C. Vantourout, Z. Liu, Q. Hou, D.
Bao, J. T. Starr, J. Chen, M. Yan, P. S. Baran, Angew. Chem. Int. Ed. 2017,
5
6, 13088–13093; Angew. Chem. 2017, 129, 13268–13273; b) See
The authors are grateful to the CNRS and the Université Paris-Est
Créteil for financial support on this work. F.D. acknowledges
Université Paris-Est Créteil for PhD grant.
reference [10].
[14] E. O. Bortnikov, S. N. Semenov, J. Org. Chem. 2021, 86, 782–793.
[
15] a) G. Silvestri, S. Gambino, G. Filardo, A. Gulotta, Angew. Chem. Int. Ed.
984, 23, 979–980; Angew. Chem. 1984, 96, 978–979; b) O. Sock, M.
1
Troupel, J. Perichon, Tetrahedron Lett. 1985, 26, 1509–1512; c) For
review, see: J. Chaussard, J.-C. Folest, J.-Y. Nedelec, J. Perichon, S. Sibille,
M. Troupel, Synthesis 1990, 369–381.
Conflict of Interest
[
16] For selected articles, see: a) R. Barhdadi, B. Simsen, M. Troupel, J.-Y.
Nédélec, Tetrahedron 1997, 53, 1721–1728; b) R. Barhdadi, J. Gal, M.
Heintz, M. Troupel, J. Périchon, Tetrahedron 1993, 49, 5091–5098; c) R.
Barhdadi, M. Troupel, J. Périchon, Chem. Commun. 1998, 1251–1252;
d) N. Sbei, B. Batanero, F. Barba, B. Haouas, M. L. Benkhoud, I. Barba,
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The authors declare no conflict of interest.
2
Keywords: Cooperative process · C(sp )À N coupling · Nickel ·
[
Sacrificial anode · Synthetic methods
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Manuscript received: February 17, 2021
Revised manuscript received: April 14, 2021
Accepted manuscript online: April 21, 2021
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© 2021 Wiley-VCH GmbH