Nickel-catalyzed decarbonylation of: N -acylated N-heteroarenes

Article abstract of DOI:10.1039/c9sc02035g

Nickel-catalyzed decarbonylation of N-acylated N-heteroarenes is developed. This method can be used to produce a variety of N-aryl heteroarenes, including pyrroles, indoles, carbazoles and phenoxazines, using benzoic acid derivatives as arylating reagents. Arylnickelamide intermediates that are relevant to the catalytic reaction were characterized by X-ray crystallography. When N-acylated benzimidazoles are used as substrates, decarbonylation accompanied 1,2-migration to form 2-arylated benzimidazoles.

Full text of DOI:10.1039/c9sc02035g

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ARTICLE
Nickel-Catalyzed Decarbonylation of N-Acylated N-Heteroarenes
Toshifumi Morioka, Syun Nakatani, Yuki Sakamoto, Takuya Kodama, Sensuke Ogoshi, Naoto
Chatani* and Mamoru Tobisu*
Received 00th January 20xx,
Accepted 00th January 20xx
Nickel-catalyzed decarbonylation of N-acylated N-heteroarenes is developed. This method can be used to produce
a variety of N-aryl heteroarenes, including pyrroles, indoles, carbazoles and phenoxazines, using benzoic acid
derivatives as arylating reagents. Arylnickelamide intermediates that are relevant to the catalytic reaction were
characterized by X-ray crystallography. When N-acylated benzimidazoles are used as substrates, decarbonylation
accompanied 1,2-migration to form 2-arylated benzimidazoles.
DOI: 10.1039/x0xx00000x
(a) Aryl halides as aryl sources (Common approach)
Introduction
NH-heteroarene
X
Because of their widespread utility in medicinal and materials
chemistry,1 methodology for preparing N-arylated heteroarenes has
continued to be a subject of intense studies. Currently, the most
powerful approach to these compounds involves the catalytic cross-
coupling of aryl halides with NH-heteroarenes (Scheme 1a).2,3 If
aromatic acids, in place of aryl halides, could be used as aryl sources
for the synthesis of N-aryl N-heteroarenes, several benefits would be
expected. For example, aromatic acids are widely available feedstock
materials, often with substitution patterns that are difficult to access
from the corresponding aryl halides, and therefore the flexibility of
synthetic planning would be enhanced. In addition, a new synthetic
strategy, such as orthogonal and late-stage transformation, would be
possible if a carboxyl group can serve as a handle with a reactivity
profile different from halides. However, despite significant progress
made in the decarboxylative cross-coupling,4 decarboxylative N-
arylation of NH-heteroarenes has not been reported, to the best of our
knowledge.5 We hypothesized that the use of an aromatic acid in the
N-arylation of NH-heteroarenes would be possible formally through a
two-step sequence, namely, amide formation (N-acylation) and
decarbonylation of the resulting amide (Schme 1b). Since a number
of reliable methods are available for amide formation,6,7 the key issue
is the development of the latter decarbonylation reaction. Except for
2-azinecarboxamides,8 catalytic decarbonylation of amides is an
unattained transformation, indicating that C(aryl)–N bond formation
via decarbonylation is clearly not a trivial task. We report herein on
the realization of this objective.
cat.
N
base
(b) Aromatic acids as aryl sources (This Work)
NH-hetero
arene
CO2H
[Ni]
CO
N
amide
formation
abundant
feedstock
amide
decarbonylation
Scheme 1 Approaches to the N-arylation of heteroarenes.
Results and discussion
We initiated our study by examining the decarbonylation of N-
acylindole 1a. To promote this reaction, we focused on the use of a
nickel catalyst, since it has been successfully used in the activation of
amides9 and in the ketone decarbonylation reaction.10 A brief
screening of ligands revealed that strong -donor ligands, such as
alkylphosphines and N-heterocyclic carbenes (NHCs), actually
afforded the desired decarbonylation product 2a in 12–31% yield
(Table 1, entries 2–7). Although the difference in the yield of 2a was
not significant between the ligands examined, a larger amount of 1a
was recovered from the reactions when phosphine ligands were used
than when NHCs were used. Therefore, further optimization was
pursued using PCy3 and 1,2-bis(dicyclohexylphosphino)ethane
(dcype). When 1 equiv of Ni(cod)2 and PCy3 were used, the
decarbonylation proceeded quantitatively, even at 80 °C (entry 8). The
catalytic decarbonylation was accomplished by running the reaction
at 180 °C using dcype as the ligand (entry 11). The reaction was not
effective when conducted at 180 °C using 20 mol% of Ni(cod)2/PCy3
(entry 9) nor at 80 °C using 1 equiv of Ni(cod)2/dcype (entry 10). We
therefore decided to use two sets of conditions for investigating the
scope and limitations of the reaction: 20 mol% of Ni(cod)2/dcype at
180 °C (condition A) and 1 equiv of Ni(cod)2/PCy3 at 80 °C (condition
B).
Department of Applied Chemistry, Faculty of Engineering, Osaka University,
Suita, Osaka 565-0871, Japan. E-mail: tobisu@chem.eng.osaka-u.ac.jp;
chatani@chem.eng.osaka-u.ac.jp
†
Electronic Supplementary Information (ESI) available: [details of any
supplementary information available should be included here]. See
DOI: 10.1039/x0xx00000x
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aCondition A: amide (0.25 mmol), Ni(cod)2 (0.050 mmol), dcVyipeew(A0r.t0ic5le0Online
Table 1 Development of the nickel-mediated decarbonylation of N-acylindole
1aa.
mmol) in toluene (1.0 mL) for 18 h at 180 °C; condition B: amide (0.25
DOI: 10.1039/C9SC02035G
mmol), Ni(cod)2 (0.25 mmol), PCy3 (0.25 mmol) in toluene (1.0 mL) for 18 h
at 80 °C bSubstituent constants from ref 11. cGC yield. dNMR yield. e3,4-
Bis(dicyclohexylphosphino)thiophene (100 mol%) was used instead of PCy3
and run at 180 °C.
O
Ni(cod)2 (20 mol%)
ligand (20 mol%)
N
N
F3C
toluene
120 °C, 18 h
F3C
A diverse array of N-acylated N-heteroarenes could be decarbonylated
using our nickel-mediated protocol (Table 3). Although a methoxy
group can be activated by Ni(0) catalysis,12 it was compatible with
this decarbonylation reaction, as exemplified by efficient reactions
when 1i and 1j were used. Several other common functional groups,
including esters 1g, amides 1k, ketones 1l, nitriles 1m, and fluorides
1n, were found to be tolerated and decarbonylation occurred
chemoselectively at the indole amide moiety. In addition to benzoic
acid derivatives, -extended analogues, such as 1o and 1p, also served
as good substrates for forming N-arylated products. The alkenyl amide
1q could be used to produce N-alkenylindole 2q in excellent yield
under condition B. Heteroarene-based carboxylic acids can also be
used in this decarbonylation reaction, as demonstrated in the reaction
of 1r. The scope of the N-heteroarene moiety was also investigated.
Substituents on the indole ring had no significant effect on the
efficiency of the reaction, thus permitting a variety of indole
derivatives to be produced via decarbonylation (1s–1ab). This
decarbonylation is not limited to indole derivatives and pyrroles 1x,
carbazoles 1y and azaindoles 1z also participated in this
decarbonylation reaction, allowing rapid access to a diverse array of
arylated heteroarenes from the corresponding carboxylic acids.
Moreover, the non-aromatic six-membered phenoxazine derivative
1aa was decarbonylated successfully, whereas the N,N-diphenyl
amide was much less reactive (10% yield, see SI for details). These
results indicate that there is a threshold for the pKa value of the parent
amine in determining whether or not the reaction will proceed (pKa in
DMSO: pyrrole 23, indole 21, carbazole 20, phenoxazine 22, and
diphenylamine 25).13. This seems to be reasonable since the C(=O)-N
bond becomes stronger as the parent amine becomes more basic,
leading to a lower reactivity in this decarbonylation reaction. In
agreement with this conclusion, a substrate derived from an electron-
deficient diphenylamine (i.e., 1ab) exhibited a significantly improved
reactivity for this decarbonylation reaction.
2a
GC yields (%)
1a
entry
ligandb
2a
1a
PPh3
PCy3
dcype
ICy
0
31
16
0
1
2
3
4
5
71
60
52
46
29
28
IMes
IMesMe
IPr
6
27
27
25
0
7
8c
9d
10c
12
>99 (88)e
PCy3
PCy3
19
65
86
0
4
dcype
dcype
11d
93 (84)e
R'
R'
ICy (R = cyclohexyl, R' = H)
IMes (R = 2,4,6-Me3C6H2, R' = H)
IMesMe (R = 2,4,6-Me3C6H2, R' = Me)
IPr (R = 2,6-iPr2C6H3, R' = H)
N
R
N
Cy2P
PCy2
dcype
R
aReaction conditions: 1a (0.25 mmol), Ni(cod)2 (0.050 mmol), ligand (0.050
mmol), in toluene (1.0 mL) for 18 h at 120 °C. bN-Heterocyclic carbene
ligands were generated in situ from the corresponding imidazolium salts by
treatment with NaOtBu (25 mol%). cNi(cod)2 (0.25 mmol) and the ligand
(0.25 mmol) were used at 80 °C. dRun at 180 °C. eIsolated yield.
The scope of the N-acyl group was initially investigated to identify
the electronic requirement for this nickel-catalyzed decarbonylation
reaction (Table 2). Under the catalytic conditions (condition A), N-
acylindoles bearing an electron-withdrawing group (i.e., 1a and 1b)
readily underwent decarbonylation, while electron-neutral (1c and 1d)
and electron-rich (1e and 1f) amides were much less reactive.11 The
yields of these less reactive amides could be improved by using
condition B, in which Ni(cod)2/PCy3 (1 equiv each) was used.
Table 2 Electronic effect of the acyl groupa.
O
N
N
condition A or B
toluene, 18 h
R
R
2a–2f
1a–1f
A: Ni(cod)2 (20 mol%), dcype (20 mol%), 180 °C
B: Ni(cod)2 (100 mol%), PCy3 (100 mol%), 80 °C
isolated yield [%]
b
p
R
A
B
1a
)
CF3
(
0.54
0.45
-0.01
0
84
--
1b
CO2Me (
)
85
--
1c
30c
23c
18c
8c
79
Ph (
)
1d
71
H (
)
1e
-0.17
-0.27
63
Me (
OMe (
)
1f
14d (33)c,e
)
2 | J. Name., 2012, 00, 1-3
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ARTICLE
This decarbonylative N-arylation allows for thVeiewoArrttihcloegOonnlinael
DOI: 10.1039/C9SC02035G
introduction of azoles into halogen and carboxylic acid functionalities.
Table 3 Scope of the nickel-catalyzed decarbonylation of N-acylated
heteroarenes.a
For example, the N-arylation of carbazole using ethyl 3-iodobenzoate
(3) occurs at the iodide site when the common copper-catalyzed
method is used,2 and the resulting carboxylic acid moiety can be
converted to another azole ring through an amidation/decarbonylation
protocol (Scheme 2).
O
N
condition A or B
toluene, 18 h
N
R
R
1g–1ab
2g–2ab
A: Ni(cod)2 (20 mol%), dcype (20 mol%), 180 °C
B: Ni(cod)2 (100 mol%), PCy3 (100 mol%), 80 °C
O
O
O
MeO
F3C
1) cat CuI
carbazole
48%
N
N
N
O
O
I
O
OEt
O
N
OMe
OH
2) NaOH
H2O
96%
3
1h
72% (A)
1g
1i
95% (A)
49% (A)
69% (B)
4
O
O
O
N
1) (COCl)2, cat. DMF
then indole 60%
MeO
F3C
N
O
N
Me
N
N
N
2) cat. Ni/dcype
(condition A)
63%
O
O
1j
1k
1l
89% (A)
85% (B)
90% (A)
56% (A)
61% (B)
5
O
N
O
O
Scheme 2 Sequential C–N bond formation using halogen and carboxyl
groups as orthogonal handles.
F
N
N
C
N
Several mechanistic experiments were conducted. A nickel-catalyzed
reaction using a mixture of 1a and 1ac provided the corresponding
decarbonylation products 2a and 2ac without the formation of any
crossover products, indicating that this reaction proceeds via an
intramolecular pathway (Scheme 3a). The reaction of amide 1a with
1 equivalent of Ni(cod)2 and dcype was monitored by 31P NMR, which
revealed that a signal derived from the Ni(CO)2(dcype) (64.0 ppm,
singlet) and two sets of doublets (57.9 ppm and 60.7 ppm, J = 13.1
Hz) appeared upon heating the mixture at 80 °C.14 These results
indicate that a relatively stable organometallic intermediate is formed.
Additional stoichiometric experiments resulted in the isolation of the
arylnickelamide complex 6a, the structure of which was
unambiguously determined by X-ray crystallography (Scheme 3b).15
Interestingly, the corresponding arylnickelamide complex 6f can also
be formed from a methoxy-substituted amide 1f under similar
conditions, although the amide 6f was much less reactive under the
catalytic conditions used. These results indicate that, the reductive
elimination from the arylnickelamide species to form a C–N bond has
higher activation barrier than the prior C–N and C–C(=O) bond
cleavage processes. Indeed, a higher temperature (>120 °C) was
required for this reductive elimination to occur to form an N-arylated
product.16 Since Ni(CO)2(dcype) is also formed as the
decarbonylation reaction proceeds, its catalytic activity was
investigated (Scheme 3c). The Ni(CO)2(dcype) was found to catalyze
the decarbonylation of 1a at 180 °C, whereas only a trace amount of
the product was formed at 120 °C. These results suggest that heating
at 180 °C is necessary for the dissociation of a CO ligand to occur to
generate a catalytically active nickel species.
F
69% (A)b
1n
1m
76% (A)
O
1o
59% (A)
90% (B)
O
O
N
N
N
N
F3C
1p
1q
1r
71% (A)
86% (B)
0% (A)
69% (A)
91% (B)
O
O
1s
R = CO2Me ( ) 76% (A)
N
N
1t
R = Me ( ) 72% (A)
F3C
F3C
1u
R = OMe ( ) 73% (A)
NBn2
1v
R = OCH2Ph ( ) 76% (A)
R
1w
69% (A)
OMe
N
O
O
O
N
N
F3C
F3C
N
F3C
70% (A)b
CF3
1x
1y
89% (A)
76% (A)
1z
O
O
N
N
O
F3C
F3C
60% (A)c
89% (A)d
1ab
1aa
60% (A)
CF3
aCondition A: amide (0.25 mmol), Ni(cod)2 (0.050 mmol), dcype (0.050
mmol) in toluene (1.0 mL) for 18 h at 180 °C; condition B: amide (0.25
mmol), Ni(cod)2 (0.25 mmol), PCy3 (0.25 mmol) in toluene (1.0 mL) for 18 h
at 80 °C. b1,3-Bis(dicyclohexylphosphino)propane (0.050 mmol) was used
instead of dcype. cRun for 48 h. dNi(cod)2 (0.25 mmol) and dcype (0.25
mmol) were used.
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 3
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(a) Crossover experiment
turnover when PCy3 is used. A similar contrast between PCy3 and
View Article Online
DOI: 10.1039/C9SC02035G
dcype was also reported in the catalytic decarbonylative cross-
O
O
Ni(cod)2 (20 mol%)
dcype (20 mol%)
coupling of phenyl esters.20
N
N
+
toluene, 180 C, 18 h
O
F3C
MeO2C
Ni
N
P
P
N
1a
(0.5 equiv)
1ac
(0.5 equiv)
A
(P = PCy2)
2d
1d
N
+
No crossover products
N
O
F3C
N
N
Ni
D
Ni
B
MeO2C
2a
93%
2ac
97%
P
P
P
P
(b) Stoichiometric reactions
O
Ni(cod)2 (1 equiv)
dcype (1 equiv)
Cy2P
PCy2
CO
N
Ni
N
+ Ni(CO)2(dcype)
N
Ni
A
A
toluene
80-120 C, 12 h
R
P
OC
R
Ni
(CO)2(dcype)
P
1a
1f
(R = CF3)
(R = OMe)
C
6a
6f
(R = CF3) 45%
(R = OMe) 52%
Scheme 4 Proposed mechanism.
6a
or
6f
N
During the course of our investigations into the decarbonylation of N-
acylated N-heteoarenes, we examined the benzimidazole derivative 7a.
To our surprise, an N-arylation product was not formed in the
Ni/dcype-catalyzed reaction of 7a but rather, C2–arylation occurred
to afford 8a. The overall reaction involves decarbonylation and 1,2-
migration of the N-substituent.21,22 Although the detailed
mechanism for this intriguing transformation remains elusive at
present, the results of several preliminary mechanistic studies are
noteworthy. First, a crossover experiment using two different N-
acylated benzimidazole derivatives resulted in the formation of
crossover products, suggesting that, unlike the decarbonylation of N-
acylated indoles shown in Table 4, an intermolecular pathway is likely
to be operative. Second, when benzimidazoles bearing a para-
substituted benzoyl group on the nitrogen atom, such as 8b, 8c and
8d, were used as substrates, small amounts of meta isomers were also
formed in addition to the expected para-substituted 2-
arylbenzimidazoles.23 This type of rearrangement was not observed in
the case of the other heteroarene-based substrates shown in Table 3.
toluene
heat
R
Yield (%)
120 C
180 C
41
R = CF3
OMe
23
0
44
6aa
ORTEP Drawing of
(c) Effect of CO ligand
O
Ni(CO)2(dcype)
(20 mol%)
N
N
toluene, 18 h
F3C
F3C
120 C: 1%
180 C: 73%
1a
2a
Scheme 3 Mechanistic Studies.
aThermal ellipsoids set at the 50% probability level. All hydrogen atoms are
omitted for clarity.15
Based on the mechanistic studies described in Scheme 3, we propose
a catalytic cycle shown in Scheme 4. In situ generated Ni(dcype) A17
serves as the catalytically active species, which initially activates a
C(acyl)–N bond of the amide 1d via oxidative addition18 to form an
acylnickelamide intermediate B. The subsequent extrusion of CO
from the acyl ligand in B leads to the formation of the carbonylnickel
species C, in which one of the phosphorus atoms of dcype is
dissociated. The dissociation of the CO ligand in C is facilitated by
the recovery of the bidentate coordination of dcype to form the
arylnickelamide complex D, which is one of the resting states of the
catalyst. C–N bond forming reductive elimination from D is one of
the difficult steps of this catalytic cycle. The higher reactivity of
electron deficient amides is in agreement with the general trend in
which C(aryl)–N bond reductive elimination proceeds more
efficiently with an aryl ligand bearing an electron-withdrawing
group.19 The dissociated CO is captured by A to form Ni(CO)2(dcype),
which is catalytically inactive but can regenerate A upon heating to
temperatures over 180 °C. The use of a PCy3 ligand instead of dcype
generates a more active complex that can more easily mediate all the
elementary steps required for the conversion of the amide 1d to the
amine 2d (i.e., oxidative addition, extrusion of CO, and reductive
elimination). However, unlike the case of dcype, there is no driving
force available for the CO dissociation step, which hampers catalyst
Third,
neither
N-phenylbenzimidazole
(S17)
nor
2-
benzoylbenzimidazole (S18) were converted into the 2-
phenylbenzimidazole (8a) under these nickel-catalyzed conditions,
excluding the intermediacy of these compounds in this migrative
decarbonylation reaction. Finally, labelling experiments using a
substrate having deuterium at the 2-position of a benzimidazole ring
revealed that the cleavage of the C(2)–H bond is not involved in a
turnover-limiting step.24 meta-Disubstituted substrates 8e–8h
underwent this decarbonylation to form the corresponding 2-arylated
products without forming regioisomers. The reaction can also be
applied to N-acylimidazole 8i, albeit in a lower yield.
4 | J. Name., 2012, 00, 1-3
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Table
4
Nickel-catalyzed 1,2-migratory decarbonylation of N-
View Article Online
acylbenzimidazole.a
1
(a) P. Ruiz-Castillo and S. L. Buchwald, Chem. Rev., 2016, 116,
DOI: 10.1039/C9SC02035G
12564; (b) G. Evano, N. Blanchard, M. Toumi, Chem. Rev., 2008, 108,
3054.
O
N
N
Ni(cod)2 (20 mol%)
dcype (20 mol%)
2
3
(a) D. S. Surry and S. L. Buchwald, Chem. Sci., 2010, 1, 13; (b) I. P.
Beletskaya and A. V. Cheprakov, Organometallics, 2012, 31, 7753.
Oxidative cross-coupling between azoles and arylboronic acids (Chan-
Lam-Evans reaction) represents another common method. K. Sanjeeva
Rao and T.-S. Wu, Tetrahedron, 2012, 68, 7735.
N
H
toluene
180 °C, 18 h
N
7a–7i
8a 8i

4
Selected reviews: (a) J. Schwarz and B. König, Green Chem., 2018,
20, 323; (b) Y. Wei, P. Hu, M. Zhang and W. Su, Chem. Rev., 2017,
117, 8864; (c) W. I. Dzik, P. P. Lange and L. J. Gooßen, Chem. Sci.,
2012, 3, 2671; (d) N. Rodríguez and L. J. Goossen, Chem. Soc. Rev.,
2011, 40, 5030; (e) W. I. Dzik, P. P. Lange and L. J. Gooßen, Chem.
Sci., 2012, 3, 2671.
N
N
N
p
p
N
N
H
N
H
H
m
m
Me
8c
F3C
8b
8a
72%
75% (p:m = 92:8)
77% (p:m = 98:2)
5
Although several decarboxylative amination reactions have been
reported to date, NH-heteroarenes cannot be used as a nitrogen-based
nucleophile. Selected examples: (a) M. PichetteꢀDrapeau, J. Bahri, D.
Lichte and L. J. Gooßen, Angew. Chem., Int. Ed., 2019, 58, 892; (b)
W. Zhao, R. P. Wurz, J. C. Peters and G. C. Fu, J. Am. Chem. Soc.,
2017, 139, 12153; (c) Z.-J. Liu, X. Lu, G. Wang, L. Li, W.-T. Jiang,
Y.-D. Wang, B. Xiao and Y. Fu, J. Am. Chem. Soc., 2016, 138, 9714;
(d) Q. Dai, P. Li, N. Ma and C. Hu, Org. Lett., 2016, 18, 5560; (e) S.
B. Lang, K. C. Cartwright, R. S. Welter, T. M. Locascio and J. A.
Tunge, Eur. J. Org. Chem., 2016, 2016, 3331. (f) Y. Zhang, S. Patel
and N. Mainolfi, Chem. Sci., 2012, 3, 3196.
The N-acylated N-heteroarenes used in this study was readily
synthesized by condensation via acid chlorides. See the Supporting
Information for details.
Synthetic utility of N-acylated azoles: A. M. Goldys and C. S. P.
McErlean, Eur. J. Org. Chem., 2012, 2012, 1877.
N
N
N
Me
F3C
p
N
H
N
H
N
H
m
MeO
8d
Me
CF3
70%b
b
8e
8f
70% (p:m = 93:7)
78%
N
N
N
MeO
F
F3C
N
H
N
H
N
H
OMe
F
CF3
6
60%b
51%
47%
8g
8h
8i
aAmide (0.25 mmol), Ni(cod)2 (0.050 mmol), dcype (0.050 mmol) in toluene
(1.0 mL) for 18 h at 180 °C. bNi(cod)2 (0.10 mmol) and dcype (0.10 mmol)
were used.
7
8
9
X. Liu, H. Yue, J. Jia, L. Guo and M. Rueping, Chem.-Eur. J., 2017,
23, 11771.
(a) R. Takise, K. Muto and J. Yamaguchi, Chem. Soc. Rev., 2017, 46,
5864; (b) J. E. Dander and N. K. Garg, ACS Catal., 2017, 7, 1413; (c)
G. Meng and M. Szostak, Org. Biomol. Chem., 2016, 14, 5690; (d) C.
Liu and M. Szostak, Org. Biomol. Chem., 2018, 16, 7998.
Conclusions
10 (a) T. Morioka, A. Nishizawa, T. Furukawa, M. Tobisu and N.
Chatani, J. Am. Chem. Soc., 2017, 139, 1416; (b) T.-T. Zhao, W.-H.
Xu, Z.-J. Zheng, P.-F. Xu and H. Wei, J. Am. Chem. Soc., 2018, 140,
586.
11 C. Hansch, A. Leo and R. W. Taft, Chem. Rev., 1991, 91, 165.
12 (a) M. Tobisu and N. Chatani, Acc. Chem. Res., 2015, 48, 1717; (b) J.
Cornella, C. Zarate and R. Martin, Chem. Soc. Rev., 2014, 43, 8081.
13 F. G. Bordwell, Acc. Chem. Res., 1988, 21, 456.
14 We also conducted a similar stoichiometric reaction using PCy3,
instead of dcype, and observed several new resonances that might be
assignable to relevant nickel species. See the Supporting Information
for details.
15 Crystal data for 6a, monoclinic, space group P21/c (no. 14), a =
16.8932(6) Å, b = 36.2820(11) Å, c = 13.0079(5) Å,  = 103.787(4)°,
V = 7743.1(5) Å3, T = 123 K, Z = 4, R1 (wR2) = 0.0825 (0.2308) for
899 parameters and 19566 unique reflections. GOF = 1.050. CCDC
1901697.
In conclusion, we have developed the first decarbonylation of N-
acylated N-heteroarenes, which allows benzoic acid derivatives to be
used as arylating agents for N-heteroarenes. Arylnickelamide
complexes were successfully isolated and characterized as viable
catalytic intermediates. 1,2-Migratory decarbonylation occurred when
N-acylated benzimidazoles were used as substrates. We expect that
the capacity of employing feedstock chemicals in synthesizing N-
arylated heteroarenes will find utility across a number of research
fields. Further studies directed at the development of new catalytic
decarbonylation reactions using simple carbonyl compounds are
currently underway in our laboratory.
Acknowledgements
This work was supported by JSPS KAKENHI (15H03811) and
Scientific Research on Innovative Area "Precisely Designed Catalysts
with Customized Scaffolding" (18H04259）from MEXT, Japan. MT
thanks Toray Science Foundation and Hoansha Foundation for financial
support. TM thanks the Program for Leading Graduate Schools:
“Interactive Materials Science Cadet Program.” for their support. We
also thank the Instrumental Analysis Center, Faculty of Engineering,
Osaka University, for assistance with HRMS.
16 (a) Reductive elimination from the MeO-substituted complex 6f
required a higher temperature (180 °C) than that needed for reaction of
the CF3-substituted complex 6a; (b) Under catalytic conditions, the
rate of product formation is expected to be much less since 6f is
generated only in a catalytic amount; (c) The yield of 2a by the
reductive elimination of 6a increased to 51% when the reaction was
conducted in the presence of Ni((CO)2(dcype) (1 equiv), indicating
that CO could accelerate the reductive elimination under catalytic
conditions.
17 The formation of Ni(dcype)(cod) under the reaction conditions was
confirmed by 31P NMR ( = 60.3 ppm, s).
18 Catalytic reactions involving the cleavage of a C(=O)–N bond of
acylpyrroles: (a) G. Meng, R. Szostak and M. Szostak, Org. Lett.,
Notes and references
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J. Name., 2013, 00, 1-3 | 5
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ARTICLE
Journal Name
2017, 19, 3596; (b) P.-Q. Huang and H. Chen, Chem. Commun., 2017,
View Article Online
53, 12584.
DOI: 10.1039/C9SC02035G
19 M. S. Driver and J. F. Hartwig, J. Am. Chem. Soc., 1997, 119, 8232.
20 X. Hong, Y. Liang and K. N. Houk, J. Am. Chem. Soc., 2014, 136,
2017.
21 The thermal isomerization of 1-carbamylimidazole to a 2-substituted
isomer was reported to occur (> 200 °C), possibly via the formation of
isocyanate and imidazole. In contrast, we confirmed that 2-
benzoylbenzimidazole (S18) remained unchanged after heating at 180
°C for 18 h in the absence of the catalyst. K. Mitsuhashi, E.-I. Itho, T.
Kawahara and K. Tanaka, J. Heterocyclic Chem., 1983, 20, 1103.
22 1-Acylimidazoles was reported to isomerize to form a mixture of 2-
and 4-acylated imidazoles photochemically. 4-Substituted isomers
were not observed in our decarbonylation reaction. S. Iwasaki, Helv.
Chim. Acta. 1976, 59, 2738.
23 This type of formation of regioisomers were reported in palladium-
catalyzed fluorination of aryl triflates: A. C. Sather and S. L.
Buchwald, Acc. Chem. Res., 2016, 49, 2146.
24 A KIE value of 1.16 was obtained. See the Supporting Information for
details.
6 | J. Name., 2012, 00, 1-3
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DOI: 10.1039/C9SC02035G
Table of Contents Entry
O
N
N
[Ni]
CO
O
N
N
N
N
H
Nickel-catalyzed decarbonylation of N-acylated N-heteroarenes is developed, allowing
aromatic acids to serve as an aryl source in arylation of NH-heteroarenes.