Amide synthesis: Via nickel-catalysed reductive aminocarbonylation of aryl halides with nitroarenes

Article abstract of DOI:10.1039/c7sc03950f

Aminocarbonylation of aryl halides is one of the most useful methods in amide synthesis, but nitroarenes have not been used as a nitrogen source in this method even though they are more economical and accessible than anilines. Reported here is the development of nickel catalysis for the first three-component reactions of aryl halides, Co₂(CO)₈, and nitroarenes under reductive conditions to produce aryl amides. A wide range of (hetero)aryl iodides and bromides as well as nitro(hetero)arenes are suitable reaction partners, and high functional group compatibility has been achieved. The method might be used for the streamlined synthesis of aryl amides.

Full text of DOI:10.1039/c7sc03950f

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ARTICLE
Amide Synthesis via Nickel-Catalysed Reductive
Aminocarbonylation of Aryl Halides with Nitroarenes
Chi Wai Cheung, Marten Leendert Ploeger, and Xile Hu*
Received 00th January 20xx,
Accepted 00th January 20xx
Aminocarbonylation of aryl halides is one of the most useful methods in amide synthesis, but nitroarenes have not been
used as a nitrogen source in this method even though they are more economical and accessible than anilines. Reported
here is the development of nickel catalysis for the first three-component reactions of aryl halides, Co2(CO)8, and
nitroarenes under reductive conditions to produce aryl amides. A wide range of (hetero)aryl iodides and bromides as well
as nitro(hetero)arenes are suitable reaction partners, and high functional group compatibility has been achieved. The
method might be used for the streamlined synthesis of aryl amides.
DOI: 10.1039/x0xx00000x
www.rsc.org/
Amides are an essential structural motif in numerous natural modest as well, as ortho-substitution was not tolerated and no
and synthetic bioactive compounds as well as organic examples of nitroheteroarenes were reported. Here we report
materials.1,2 One of the most commonly used methods to the first aminocarbonylation of aryl halides with nitroarenes
synthesize
aryl
amides
is
palladium-catalyzed using abundant and commercially available nickel catalysts
aminocarbonylation of aryl halides 3,4 (Figure 1(a)). Typically an (Figure 1(d)). It should be noted that nickel catalysis has hardly
alkyl amine or aniline is used as the nitrogen source. Because been used for aminocarbonylation in general. To our knowledge,
nitroarenes are generally less expensive than the corresponding only one example of Ni-catalyzed aminocarbonylation of aryl
anilines and most anilines are prepared by reduction of the iodides with amines was previously reported.8 Our method has
corresponding nitroarenes, the direct use of nitroarenes will broad scope and high functional group compatibility, allowing
save reagent cost and eliminate at least one process step. the rapid synthesis of a diverse class of aryl amides.
Moreover, the nitro group exhibits orthogonal reactivity to the
amine group, so functional group typically incompatible with
Pd-catalysed aminocarbonylation with amines
(a)
nucleophilic amination reactions, such as ketones, esters, alkyl
halides, and alcohols, might be tolerated using nitroarenes as the
starting reagents. While a number of studies have emerged to
exploit the advantages of nitroarenes as a nitrogen source,5
there is no prior report of using nitroarenes in
aminocarbonylation of aryl halides. Only a few examples of
aminocarbonylation of other carbon nucleophiles are known.
For example, Beller and co-workers reported a Pd-catalyzed
aminocarbonylation of olefins with nitroarenes using
dihydrogen as reductant (Figure 1(b)).6 The nitroarenes
appeared to be reduced in-situ to anilines in those reactions.
Driver and co-workers reported a Pd-catalyzed, directing-group-
assisted aminocarbonylation of aryl C-H bonds with nitroarenes
and molybdenum hexacarbonyl (Mo(CO)6) (Figure 1(c)).7
Interestingly, nitroarenes were proposed to be first reduced to
O
Pd
or
catalyst
surrogates
+
Ar
X
R-NH2
alkyl,
R
CO CO
Ar
N
H
=
aryl
R
Pd-catalysed aminocarbonylation of olefins with nitroarenes
(Beller)
(b)
O
Pd catalyst
Alkyl
Ar
+
Ar-NO2
Alkyl
N
H
H
CO /
2
Pd-catalysed
C-H
directing-group-assisted
(c)
aminocarbonylation with nitroarenes
(Driver)
DG
O
DG
Ar
Pd catalyst
+
H
Ar'
nitrosoarenes
which
directly
took
part
in
the
Ar'-NO2
Ar
N
Mo(CO)6
aminocarbonylation without being reduced to anilines.
Nevertheless, due to the requirement of a strong directing group,
the carbon nucleophiles were limited to pyridine, pyrimidine or
indazole-substituted 2-aryl groups. The scope of nitroarenes was
H
=
DG directing
group
Ni-catalysed reductive aminocarbonylation with nitroarenes
(d)
work)
(this
O
catalyst
Ni(II)
Co
+
X
Ar'-NO2
Ar
Ar'
a.Laboratory of Inorganic Synthesis and Catalysis, Institute of Chemical Sciences
and Engineering, Ecole Polytechnique Fédérale de Lausanne (EPFL), ISIC-LSCI, BCH
3305, Lausanne 1015 (Switzerland). E-mail: xile.hu@epfl.ch; web:
http://lsci.epfl.ch.
Ar
N
2(CO)8
or
Zn Mn, TMSX
=
X
Br
I,
H
Figure 1. Various methods of aminocarbonylation.
† Electronic Supplementary Information (ESI) available: Experimental and Spectra
Data. See DOI: 10.1039/x0xx00000x
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 1
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We recently reported that, under reductive conditions, bidentate nitrogen-based ligands, Mn reductant, anVdiewotAhrteicrlepOonllianer
nitroarenes could be transformed into nitrosoarenes5d and aprotic solvent led to diminishments in yields (Table 2, entries 2-
DOI: 10.1039/C7SC03950F
diazoarenes,5e which served as the nitrogen sources in Fe- 6). Particularly, the use of other CO surrogates (Fe(CO)6 and
catalyzed amination of alkyl halides,5d and Ni-catalyzed Mn(CO)6, Table 2, entries 7 and 8), CO (entry 9), and other
amidation of esters and transamidation,5f respectively. We transition metal catalysts (iron, cobalt, copper, manganese (Table
hypothesized that a Ni-catalyzed aminocarbonylation of aryl 2, entries 10-13) resulted in a significant drop of yields. Without
halides with nitroarenes might be operative following
a Ni(glyme)Cl2, only a trace of 2a was formed, suggesting that Ni is
mechanistic pathway displayed in Figure 2.9-11 Initially, a Ni(II) the real catalyst and Co in Co2(CO)8 is not (Table 2, entry 14). L1
precatalyst is reduced by an inexpensive reductant (Zn or Mn) was also essential for the reaction to significantly enhance the
to a Ni(0) species, which then activates an aryl halide via yield (Table 2, entry 15). Because some reduction of nitrobenzene
oxidative addition to give
a Ni(II)-aryl intermediate. The to aniline was occurring as a side reaction, a slight excess (1.5
insertion of CO to the Ni(II)-aryl species gives a Ni(II)-acyl equiv.) of nitrobenzene was needed.
complex. Meanwhile, in the presence of a halotrimethylsilane
additive (TMSX), a nitroarene is reduced by the reductant to
Table 1. Optimization of catalytic reductive aminocarbonylation
form a nitrosoarene or a diazoarene, or other reduced species
such as N-phenylhydroxylamine or aniline,5d-5f which could then
react with the Ni-acyl species to produce an amido anion, which
upon acidic workup, furnished the desired amide. If aniline is
involved, then the C-N bond forming step is analogous to that in
a standard C-N coupling and Ni(0) species is regenerated
directly. If a less reduced nitrogen species is involved, then
electron transfer from the metal reductant is necessary to
regenerate the Ni(0) species, and the mechanism can be rather
complicated. Nevertheless, previous work on Ni-catalyzed
reductive amidation5e and transamidation5f suggests the
feasibility of such a transformation.
of aryl iodide with nitroarene.
mol
%)
%)
equiv)
Ni(glyme)Cl2 (10
mol
t-Bu
O
L1
dtbpy
10
,
(
+
t-Bu
NO2
PhI
Co
Ph
N
2(CO)8 (0.8
TMSCl
H
1a
(1 equiv.)
2a
equiv.)
mol
%)
Zn
(2 equiv.),
(10
3
DMF, 120 o 16 h
(1.5
C,
t-Bu
t-Bu
MeO
OMe
N
N
N
N
N
N
N
N
L2
L3
L1
L4
Entry
1
Variations from ‘standard conditions’
none
Yielda
100
92
O
2
L2 instead of L1
H+
O
L NiII
M0
Ar
Ar
3
L3 instead of L1
91
Ar
N
Ar
N
=
Zn, Mn)
(M
H
4
L4 instead of L1
87
M2+
5
Mn (2 equiv) instead of Zn
NMP instead of DMF
58
Ar NH2
or
ArX
L Ni0
6
85
Ar NHOH
7
Fe(CO)5 (2 equiv) instead of Co2(CO)8
Mo(CO)6 (2 equiv) instead of Co2(CO)8
CO (1.4-2.4 bar) instead of Co2(CO)8
26
Ar NO
Ar
8
31
Ar
X
1/2 N N
9
6-16
10
L NiII
e-
Ar NO2
Ar
+ n
10
11
12
13
14
15
FeBr2 (10 mol %) instead of Ni(glyme)Cl2
CoCl2 (10 mol %) instead of Ni(glyme)Cl2
CuBr2 (10 mol %) instead of Ni(glyme)Cl2
MnCl2 (10 mol %) instead of Ni(glyme)Cl2
No Ni(glyme)Cl2
<5
<5
O
M2+
TMSO-
TMS
M0
TMSX
<5
Ar
CO
L NiII
<5
2O
X-
No L1
55
X
a Corrected GC yield using n-dodecane as an internal standard.
Figure 2. Mechanistic design of Ni-catalyzed reductive
aminocarbonylation of aryl halides with nitroarenes.
The optimization conditions in Table 1 could be applied for
the aminocarbonylation of various aryl iodides (Figure 3).
Electron-neutral (3a), -rich (3h, 3n-3p), and -deficient aryl
iodides (3r-3v), as well as six- (pyridyl, 3dd) and five-
membered (pyrazolyl, 3ee) hereroaryl aryl iodides, were all
suitable coupling partners. Likewise, electron-rich (3a, 3f, 3j,
3n, 3p, 3r, 3t, 3aa, 3bb) and -deficient nitroarenes (3b, 3h, 3w)
We commenced the study by examining the reaction of
iodobenzene (1a) with 1-tert-butyl-4-nitrobenzene (2a) (Table
1). Because CO gas is inconvenient to handle in the setting of a
synthetic laboratory, we decided to employ a metal polycarbonyl
reagent as the CO surrogate. After a screening of reaction
parameters, we found that the optimized conditions involved the
use of dimethylformamide (DMF) as solvent, Ni(glyme)Cl2 (10 mol
%) as catalyst, 4,4’-di-tert-butyl-2,2’-dipyridyl (dtbpy, L1) as
ligand, Zn powder (2 equiv) as reductant, chlorotrimethylsilane
(TMSCl ,10 mol %) as Zn-activating reagent, and dicobalt
octacarbonyl (Co2(CO)8) as CO surrogate (0.8 equiv) (Table 1,
entry 1).12 The optimal loading of 2a was 1.5 equiv., and the
reaction was completed after 16 h at 120 oC. After an acidic
workup, the desired amide product, N-4-tert-butylphenyl
benzamide (3), was obtained quantitatively. The use of other
also reacted smoothly. Particularly,
a
wide range of
nitrohereroarenes could be used, including pyridine (3e, 3k),
pyrrole (3f), N-H free indole (3g), benzothiazole (3l), coumarin
(3m), carbazole (3p), pyrazole (3q), oxazole (3x), and
benzoxazole (3cc). Sterically bulky aryl iodide (3q) and
nitroarenes (3i, 3j) also reacted equally well. Ortho-substitution
on the nitroarene was tolerated (3i, 3j), which is a significant
improvement in scope compared to the Pd-catalyzed
aminocarbonylation method developed by Driver.7 A broad
2 | J. Name., 2012, 00, 1-3
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ARTICLE
mol
mol
%)
%)
equiv)
Ni(glyme)Cl2 (10
range of functional groups were compatible on both aryl iodide
O
and nitroarene substrates, such as thio (3a, 3t), flVuioewroArt(ic3lebO, n3linee,
dtbpy
10
+
(L1,
Ar
I
Ar' NO2
Ar'
DOI: 10.1039/C7SC03950F
Ar
N
Co
2(CO)8 (0.8
TMSCl
H
(1 equiv.)
(1.5 equiv.)
mol
3s), chloro (3c, 3r, 3gg), bromo (3d), ether (3c, 3h),
trifluoromethoxy (3t), trifluoromethyl (3u, 3y), nitrile (3h, 3v),
olefin (3n), tosyl (3w), amino (3bb), and protected functional
groups such as for aldehyde (3y), ketone (3z), and alcohol (3aa).
When the optimal conditions in Table 1 were applied for the
aminocarbonylation of bromobenzene (1b) with 2a, the yield of
N-t-tert-butyl phenyl benzamide was only 5% (Table 2, entry 1).
Further optimization showed that by replacing Zn with Mn (5
equiv.), TMSCl with iodotrimethylsilane (TMSI, 1.5 equiv.), and
L1 with 4,4’-dimethoxy-2,2’-dipyridyl (L4), and by enhancing
the loading of Co2(CO)8 to 1.2 equiv., the desired amide product
3 could be obtained in 87% yield (Table 2, entry 2). The use of
other ligands, reductant, additives, and lower loadings of TMSI
and Co2(CO)8 resulted in significant diminishment in yields
(Table 2, entries 3-9). Again, both Ni catalyst and L4 were
essential (Table 2, entries 10 and 11). The use of Mn instead of
Zn led to a significant enhancement of yield (Table 2, entries 2
and 5). We hypothesize that a higher reducing power from Mn
might be necessary to reduce the relevant Ni(II) species to Ni(0),
and a more electron-rich ligand L4 might be essential to
promote the oxidative addition of a aryl-bromide bond.
Zn
%)
(2 equiv.),
(10
DMF, 120 o 16 h
C,
SMe
Me
OMe
Cl
O
O
O
N
H
N
H
F
N
H
3c 75%
,
3a
3b
73%
67%
66%
66%
,
,
Me
Br
N
N
O
O
O
F
N
H
N
N
H
H
3d
3e
,
,
3f 42%
,
Me
CN
O
O
O
N
H
N
H
N
N
H
H
MeO
MeO
Me
3g 47%a
55%b
,
3h
,
3i
91%
,
N
OMe
N
S
O
O
O
Me
N
H
N
N
H
H
Me
MeO
MeO
MeO
52%a
3l
63%
,
3j
85%
,
3k
,
O
O
O
O
N
H
N
H
The conditions in Table 2 were then applied for the
aminocarbonylation of various aryl bromides (Figure 4). Both
electron-rich (4a) and -deficient (4b-4e, 4g, 4h) aryl bromides
coupled efficiently. Various hereroaryl bromides were also
suitable coupling partners, including quinoline (4j), indole (4k),
indazole (4l), benzofuran (4m), carbozaole (4n), and
benzothiophene (4o). Naphthyl (4i) could be adopted as
substrate as well. Additionally, electron-rich (4b-4f, 4h, 4j, 4m)
and -deficient nitroarenes (4i), nitroheteroarenes (quinoline
(4a), 1,3-benzodioxole (4f)), polycyclic nitroarene (4h), and
sterically bulky nitroarene (4p) also reacted equally well. A wide
range of functional groups were compatible on both aryl
bromides and nitroarenes substrates, such as ethers (4a, 4c,
4m), fluoro (4b, 4p), amine (4b, 4f), ketone (4c, 4g), amide (4d),
trifluoromethyl (4e, 4h, 4i). Aminocarbonylation also worked
for a vinyl bromide (4p). Alkyl halides, on the other hand, could
not be used as substrates.
EtO
MeO
43%a
O
62%a
3m
,
3n
,
O
t-Bu
O
N
O
O
N
H
N
H
t-Bu
60%a
Me
t-Bu
3o
,
3p
62%
,
N
N
t-Bu
O
O
Me
O
N
N
H
H
N
H
Cl
F
3q 42%c
3r 55%
3s
60%
,
,
,
S
t-Bu
t-Bu
O
O
O
N
H
N
N
H
H
F3CO
MeO
F3C
NC
3t 41%d
3u 55%
3v 57%
,
,
,
Et
N
O
OTs
O
O
O
O
O
N
H
F3C
Table 2. Optimization of catalytic reductive aminocarbonylation
N
MeO
N
H
H
of aryl bromide with nitroarene.
3w 44%
46%[a]
3y
,
54%
3x
,
,
mol
%)
t-Bu
Ni(glyme)Cl2 (10
mol
O
OTBDMS
Me
L4
%)
O
O
(10
+
t-Bu
NO2
PhBr
Me
NMe2
Co
equiv)
Ph
N
2(CO)8 (1.2
O
O
O
H
1b
(1 equiv.)
2a
equiv.)
Mn
TMSI
(5 equiv.), (1.5 equiv.)
F3C
3
Me
DMF, 120 o 16 h
(1.5
N
H
N
H
N
H
C,
Entry
Variations from ‘standard conditions’
Table 1, entry 1
Yielda
3z
80%
,
3aa
50%
,
3bb
73%
,
t-Bu
O
1
2
5
t-Bu
O
O
O
Me
N
N
none
87
65
51
8
N
N
N
N
N
H
H
H
3
L1 instead of L4
81%a
51%c
t-Bu
3cc
,
Me
3dd
,
3ee
66%
Cl
,
4
L2 instead of L4
O
O
5
Zn (5 equiv.) instead of Mn
TMSBr (1.5 equiv.) instead of TMSI
TMSCl (1.5 equiv.) instead of TMSI
TMSI (1 equiv.) instead of (1.5 equiv.)
N
N
H
H
6
27
31
74
65
36
69
t-Bu
e
3ff 59%
44%
,
,
3gg
(53%)
7
Figure 3. Scope of Ni-catalyzed reductive aminocarbonylation of
aryl iodides with nitroarenes. a Ni(glyme)Cl2 (15 mol %), L1 (15
mol %), Co2(CO)8 (1 equiv), DMF (1.4 mL). b Co2(CO)8 (1 equiv). c
Ni(glyme)Cl2 (15 mol %), L1 (15 mol %), Co2(CO)8 (1 equiv).
DMF (1.4 mL).
8
9
Co2(CO)8 (1 equiv.) instead of (1.2 equiv.)
10
11
No Ni(glyme)Cl2
d
No L4
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 3
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a Corrected GC yield using n-dodecane as an internal standard.
yield of product (<20%) (Figure 6b, (i) and (ii)), N-phenyl
hydroxylamine and aniline reacted to give the proVdieuwctAsrticinle O5n6li%ne
mol
%)
DOI: 10.1039/C7SC03950F
Ni(glyme)Cl2 (10
O
mol
L4
%)
+
(10
Ar Br
Ar' NO2
equiv.)
and 48% yields, respectively (Figure 6b, (iii) and (iv)), which
were comparable to the parent reaction (Figure 6a). It is noted
aminocarbonylation of tert-butylaniline has yields 30-50%
lower than reactions using its corresponding nitroarene
compound (Table S1, entries 28-29). The difference in yields
might be due to different effective concentrations of reagents
(anilines, Zn, Co2(CO)8) in the two protocols. Nitrobenzene might
be reduced by CO to form phenyl isocyanate.7,14 However, phenyl
isocyanate reacted to give only a trace of product (Figure 6b,
(v)). Azobenzene and phenyl isocyanate are also incompatible
with conditions simulating (partial) consumption of dicobalt
octacarbonyl (Table S3). Thus, based on the reactivity studies of
possible intermediates derived from nitrobenzene, both N-
phenyl hydroxylamine and aniline are possible intermediate in
the reductive aminocarbonylation reaction. Direct reaction of
nitrobenzene cannot be rule out neither. A more detailed
mechanism of this aminocarbonylation reaction is subject to
further study.
Ar'
Ar
N
Co
equiv)
TMSI
(1.5 equiv.)
2(CO)8 (1.2
H
(1 equiv.)
(1.5
Mn
(5 equiv.),
DMF, 120 o 16 h
C,
N
OMe
NHPh
O
O
O
N
N
N
H
H
H
Ph
MeO
Et2N
F
71%a
4a
,
4b
4c
47%
,
73%
81%
,
O
O
Me
Me
O
O
O
O
N
H
Me2N
N
H
OMe
N
H
F3C
O
4d
81%
,
4e
,
4f
71%
,
CF3
OMe
O
O
O
O
Et
N
H
F
3C
N
N
H
H
4g
4h
51%
50%
58%a
4i
,
,
,
t-Bu
OMe
t-Bu
O
O
O
Reductive aminocarbonylation with nitrobenzene
(a)
N
N
N
H
Me
N
H
H
mol
%)
N
N
Ni(glyme)Cl2 (10
mol
N
O
4l
4k
53%a
,
Bn
, 43%
L1
4j
80%
O
,
%)
(10
+
PhI
equiv.)
Ph NO2
equiv.)
Ph
Ph
N
t-Bu
Co
equiv)
2(CO)8 (0.8
O
O
H
(1
(1.5
mol
(10
Zn
TMSCl
%)
equiv.),
(2
55%
DMF, 120 o 20 h
N
H
N
Me
C,
H
N
O
46%a
70%
Et
4m
4n
,
,
Reductive aminocarbonylation with
reduced nitrogen
species
possible
(b)
OMe
OMe
mol
%)
Ni(glyme)Cl2 (10
mol
O
O
O
L1
%)
(10
2(CO)8 (0.8
TMSCl
+
S
PhI
Ph
X
Ph
N
N
H
Ph
N
H
Co
equiv.),
equiv)
equiv.)
H
(1
equiv.)
(1.5
mol
Zn
%)
(0.5
(10
DMF, 120 o 20 h
F
4o
4p
44%
,
83%
,
C,
Ph NO
19%
7%
(i)
Figure 4. Scope of Ni-catalyzed reductive aminocarbonylation of
aryl bromides with nitroarenes. Ni(glyme)Cl2 (15 mol %), L4
1/2 Ph N=N Ph
(ii)
a
Ph NHOH
Ph NH2
56%
48%
(iii)
(iv)
(v)
(15 mol %).
<
5%
Ph
N
CO
Figure 6. Studies of the nitrogen-containing intermediate in Ni-
catalyzed reductive aminocarbonylation of aryl halide with
nitrobenzene.
To
demonstrate
an
application,
the
current
aminocarbonylation method was applied for the synthesis of a
bioactive molecule, 5, which is a potent allosteric modulator of
metabotrpic glutamate receptors
4 (mGluR4) for potential
treatment of Parkinson’s disease (Figure 5).13 Indeed, our
Conclusions
method allowed the synthesis of 5 in 63% yield.
In conclusion, a new Ni-catalyzed methodology has been
developed to enable the first aminocarbonylation of
Cl
mol
%)
Ni(glyme)Cl2 (15
mol
O
Cl
L1
N
I
%)
(15
N
(hetero)aryl
iodides
and
bromides
with
N
OMe
+
Co
equiv)
2(CO)8 (1
TMSCl
H
O2N
OMe
nitro(herero)arenes. Broad scope and high group
compatibility have been demonstrated. The direct use of
nitroarenes in place of anilines provides potential
advantages in cost and step-economy. Application in
streamlined synthesis of aryl amides can be anticipated.
mol
(10
Zn
%)
(2 equiv.),
DMF, 120 o 16 h
allosteric modulators of mGluR4
(1 equiv.)
C,
(1.5 equiv.)
63%
Figure 5. Application of reductive aminocarbonylation in
synthesis of bioactive molecule 5.
To probe the nature of the nitrogen-containing intermediate in
the reductive aminocarbonylation, reactions with viable
intermediates from reduction of nitrobenzene were studied.
Nitrobenzene could be reduced to nitrosobenzene, N-phenyl
hydroxylamine, azobenzene, and anilines under the reductive
conditions5d-5f (Figure 2). In the test reaction using nitrobenzene,
the desired aryl amide was formed in 55% yield (Figure 6a).
While nitrosobenzene and azobenzene only reacted to give low
Conflicts of interest
There are no conflicts to declare.
Acknowledgements
4 | J. Name., 2012, 00, 1-3
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Chemical Science
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Journal Name
ARTICLE
unlikely the source of carbonyl monoxide for amide
This work is supported by the EPFL and the NoNoMeCat Marie
Skłodowska-Curie training network funded by the European Union
under the Horizon 2020 Program (675020-MSCA-ITN-2015-ETN).
View Article Online
formation.
DOI: 10.1039/C7SC03950F
13 D. W. Engers, C. M. Niswender, C. D. Weaver, S. Jadhav, U. N.
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14 (a) W. B. Hardy and R. P. Bennett, Tetrahedron Lett., 1967,
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7
7
6
7
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carbonyl as a CO surrogate and Ni(II)(dtbpy) as a precatalyst
has been reported. See: A. C. Wotal, R. D. Ribson and D. J.
Weix, Organometallics, 2014, 33, 5874.
12 DMF can decompose at high temperature to form CO and
dimethylamine, see: J. Muzart, Tetrahedron, 2009, 65, 8313.
During the initial optimization, we found that in the absence
of Co2(CO)8, only diarylamine was formed in modest yield via
the reductive coupling of aryl iodide with nitroarene without
the formation of N-aryl benzamide. Thus, DMF solvent is
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J. Name., 2013, 00, 1-3 | 5
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Chemical Science
Page 6 of 6
View Article Online
DOI: 10.1039/C7SC03950F
A nickel-catalysed reductive aminocarbonylation of (hetero)aryl halides employing readily
available nitro(hetero)arenes as the nitrogen sources has been developed.
10 % Ni(glyme)Cl2 / L1
+
+
Ar
I
Ar' NO2
Ar' NO2
Co2(CO)8 , Zn, TMSCl
DMF, 120 o
O
C
Ar'
Ar
N
H
10 %
Ni(glyme)Cl2 / L4
Ar Br
t-Bu
Co2(CO)8 , Mn, TMSI
DMF, 120 o
MeO
C
t-Bu
OMe
N
N
N
N
L1
L4