Palladium-catalyzed aminocarbonylation of aryl iodides with amines: efficient access to bidentate amide directing groups

Article abstract of DOI:10.1007/s11243-020-00418-4

A new route to bidentate amide directing groups has been developed via the palladium(II)-catalyzed aminocarbonylation. Under atmospheric carbon monoxide pressure, using commercially available aryl iodides and aromatic amine derivatives as substrates, the three-component reaction proceeded smoothly to give the desired products in moderate-to-excellent yields with good functional-group compatibility.

Full text of DOI:10.1007/s11243-020-00418-4

Transition Metal Chemistry
https://doi.org/10.1007/s11243-020-00418-4
Palladium‑catalyzed aminocarbonylation of aryl iodides with amines:
efcient access to bidentate amide directing groups
Yanqing Wang1 · Tao Wang2 · Xiaosha Wang2 · Lantao Liu2,3 · Guoliang Mao1
Received: 5 July 2020 / Accepted: 5 August 2020
© Springer Nature Switzerland AG 2020
Abstract
A new route to bidentate amide directing groups has been developed via the palladium(II)-catalyzed aminocarbonylation.
Under atmospheric carbon monoxide pressure, using commercially available aryl iodides and aromatic amine derivatives as
substrates, the three-component reaction proceeded smoothly to give the desired products in moderate-to-excellent yields
with good functional-group compatibility.
Introduction
as 8-aminoquinoline [12–19], amide-oxazoline [20–27],
2-(pyridin-2-yl)isopropylamine [28–33], 2-aminopyridine
1-oxide [34–37], 2-aminophenylpyrazole [38], etc. In recent
times, signifcant advancement has been made in the highly
selective C–H activation of bidentate amides using Pd, Ni,
Cu and Co as catalysts. Hence, the development of sim-
ple and efcient approaches for the synthesis of bidentate
amide directing groups containing various heteroatoms is
an attractive research topic. Traditionally, the synthesis of
amides with such a scafold involves the acylation of acyl
chlorides with amines [27, 37]. Nevertheless, the direct ami-
nocarbonylation of aryl halides with amines provides a more
straightforward option [39–41]. The reason is that, CO is
an inexpensive and readily available carbonyl source and it
is also valued because of its simplicity and atom economy.
Recently, we reported the synthesis of ferrocene indanone
derivatives via the trinuclear N-heterocyclic carbene
palladium(II)-catalyzed cyclocarbonylation of o-bromoar-
ylferrocenes with CO as the suitable starting materials [42].
Inspired by above content, we herein planned to develop a
general and efcient method for the synthesis of bidentate
amide directing groups, which should be proved to be excel-
lent substrates in C–H activation reaction (Scheme 2).
Transition metal-catalyzed C–H bond activation and func-
tionalization is one of the most important and frequently
used methods for the formation of carbon–carbon as well
as carbon–heteroatom bonds in modern organic synthetic
chemistry [1–9].1 Among these, the C–H functionalization
assisted by bidentate amide directing group has attracted
considerable attention because the chelation-directed strat-
egy can provide a reliable and robust tool to enhance the
efciency and control the selectivity of C–H activation via
the formation of a pincer-type metallacycle (Scheme 1)
[10]. Since the pioneering work of Daugulis et al. [11], a
wide variety of bidentate amide directing groups have been
synthesized and applied in the C–H functionalizations such
Electronic supplementary material The online version of this
article (https://doi.org/10.1007/s11243-020-00418-4) contains
supplementary material, which is available to authorized users.
* Tao Wang
wt67751726@126.com
* Guoliang Mao
maoguoliang@nepu.edu.cn
1
College of Chemistry and Chemical Engineering,
Northeast Petroleum University, Daqing 163318,
People’s Republic of China
2
Henan Engineering Laboratory of Green Synthesis
for Pharmaceuticals, College of Chemistry and Chemical
Engineering, Shangqiu Normal University, Shangqiu 476000,
People’s Republic of China
3
1
College of Chemistry, Zhengzhou University,
For selected reviews on transition metals catalyzed C–H function-
Zhengzhou 450001, People’s Republic of China
alization.
Vol.:(0123456789)
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Transition Metal Chemistry
Scheme 1 Transition-metal-mediated chelation-assisted C–H functionalization
Scheme 2 Synthesis of the bidentate amide directing groups
NMR spectra, and their analytical data are given in the
Supporting Information.
Experimental
General remarks
Results and discussion
Solvents were dried by standard methods and freshly
distilled prior to use if needed. All other chemicals were
used as purchased. The aromatic amine derivatives were
prepared according to the literature methods [27, 37, 43,
44]. NMR spectra were recorded on a Bruker DPX 400
instrument using TMS as an internal standard.
Our initial studies focused on developing an optimum set
of reaction conditions for the carbonylative reaction. The
experiments were carried out using 2-(4,5-dihydrooxazol-
2-yl)aniline (0.20 mmol) and iodobenzene (0.30 mmol) as
the reactants, plus Pd(OAc)2 (10.0 mol%) as the catalyst, in
toluene (2.0 mL) at 100 °C under a CO atmosphere, with the
results shown in Table 1. The yield of N-(2-(4,5-dihydroox-
azol-2-yl)phenyl)benzamide (3aa) was strongly dependent
on the choice of the base (Table 1, entries 1–13) [45]. K3PO4
was by far the most efective base (Table 1, entry 8). We
have also explored the efect on the reaction yield of other
variables, such as the palladium catalyst, the temperature,
and the reaction time (Table 1, entries 14–22). The optimum
reaction conditions thus far developed employ 1 atm of car-
bon monoxide, 1 equiv of the 2-(4,5-dihydrooxazol-2-yl)ani-
line (0.20 mmol), 1.5 equiv of the iodobenzene (0.30 mmol),
10 mol% of commercially available PdCl2(CH3CN)2, and 2
equiv of anhydrous potassium phosphate in toluene (2 mL)
at 100 °C for 15 h; this procedure provided a yield of 96%
(Table 1, entry 15).
General procedure for the catalytic
aminocarbonylation
Toluene (2.0 mL), K3PO4 (84.9 mg, 0.40 mmol),
PdCl2(CH3CN)2 (5.2 mg, 10 mol %), iodobenzene
(61.2 mg, 0.30 mmol), and the 2-(4,5-dihydrooxazol-2-yl)
aniline (32.4 mg, 0.20 mmol) were stirred under an Ar
atmosphere at room temperature for 10 min. The mixture
was fushed with CO and ftted with a CO flled balloon.
The reaction mixture was heated to 100 °C with vigorous
stirring for 15 h. After cooling, the mixture was evaporated
and the product was isolated by preparative TLC on silica
gel plates to aford the corresponding bidentate directing
group complex. The purifed products were identifed by
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Transition Metal Chemistry
Table 1 Optimization of reaction conditions for the carbonylative of iodobenzene with 2-(4,5-dihydrooxazol-2-yl)anilinea
Entry
Cat
Base
Yield (%)b
1
2
3
4
5
6
7
8
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
KOtBu
NaOtBu
Cs2CO3
Na2CO3
K2CO3
Li2CO3
NaHCO3
K3PO4.
K3PO4 3H2O
KH2PO4
NaOAc
NaOH
73
65
52
72
74
19
49
83
81
24
33
5
29
90
96
83
84
81
66
86
80
85
9
10
11
12
13
14
15
16
17
18
19
20c
21d
22e
Pd(OAc)2
Et3N
Pd(PPh3)4
PdCl2(CH3CN)2
PdCl2(PPh3)2
PdCl2(dppf)
Pd2(dba)3
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
PdCl2
PdCl2(CH3CN)2
PdCl2(CH3CN)2
PdCl2(CH3CN)2
aAll reactions were carried out using 2-(4,5-dihydrooxazol-2-yl)aniline (0.20 mmol), iodobenzene (0.30 mmol), base (2.0 equiv), plus catalyst
(10.0 mol%) in toluene (2.0 mL) at 100 °C for 15 h
bIsolated yields
cReaction temperature was 80 °C
dReaction temperature was 60 °C
eReaction time was 12 h
Under the optimized reaction conditions, a variety of
aryl iodides were employed to further investigate the scope
of the catalyst system. As demonstrated in Scheme 3, most
of the carbonylations proceeded efciently to give the cor-
responding bidentate directing group complexes 3aa–3al
in good to excellent yields. Both electron-donating includ-
ing –CH3 (3ab–3ae), –OCH3 (3af–3ag), –tBu (3ah) and
withdrawing substitutes including –F (3ai), –Br (3aj),
–CF3 (3ak) on the aryl iodides were well tolerated and
gave good to excellent yields (73–89%). Meaningfully, the
case of 1-iodonaphthalene also aforded the desired prod-
uct in satisfactory yield under the present reaction condi-
tions (3al). However, when heteroaromatic aryl iodides,
such as 2-iodothiophene were used as the substrate, a
relatively low yield was obtained (30% for 3am). We have
also attempted to employ iodocyclohexane and 1-iodobu-
tane in our method. The yields of products 3an and 3ao
1 3

Transition Metal Chemistry
aAll reactions were carried out using 2-(4,5-dihydrooxazol-2-yl)aniline (0.20 mmol),
aryl iodides (0.30 mmol), K3PO4 (2.0 equiv), plus PdCl2(CH3CN)2 (10.0 mol%) in
toluene (2.0 mL) at 100 oC for 15 h.
Scheme 3 Substrate scope for the carbonylative of aryl iodides with 2-(4,5-dihydrooxazol-2-yl)anilinea
were relatively low, but they were difcult to synthesize
in present methods.
anilines were also applicable under the current reaction con-
ditions, afording the desired products in acceptable yields
(3be–3bg, 66–76%). As for product 3bh, the possible reason
for the decrease in yield was the steric hindrance efect dur-
ing the reaction. Overview, bidentate directing group build-
ing blocks were synthesized in a convenient mode with CO
as the suitable starting material.
After evaluating the scope of the aryl iodide coupling
partner, we tested a wide range of aromatic amine derivatives
to demonstrate the generality of the protocol (Scheme 4).
For example, aromatic amine derivatives including 8-ami-
noquinoline, 2-aminopyridine, 1-oxide 2-aminopyridine,
2-(4,5-dihydro-1H-imidazol-2-yl)aniline could serve as
viable substrates in the reaction for the successful production
of the corresponding bidentate directing group complexes
(3ba–3bd). The various substituted 2-(1H-pyrazol-1-yl)
On the basis of the mechanism of previous reports [39,
40] and our results, a putative reaction mechanism was
then proposed in Scheme 5. First, aryl iodides 2 are oxida-
tively added to the in situ formed palladium(0) complexes
resulting in intermediate I, followed by CO insertion to
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Transition Metal Chemistry
aAll reactions were carried out using aromatic amine derivatives (0.20 mmol),
iodobenzene (0.30 mmol), K3PO4 (2.0 equiv), plus PdCl2(CH3CN)2 (10.0 mol%) in
toluene (2.0 mL) at 100 oC for 15 h.
Scheme 4 Substrate scope for the carbonylative of iodobenzene with aromatic amine derivativesa
produce the coordination of carbon monoxide II, which is
inserted into the Pd–C bond to give the intermediate III.
Then the intermediate III is ready for the coordination of
the amine nucleophile 1 and to convert to intermediate
IV vis eliminating a molecule of HI by a base. The reduc-
tive elimination leads to the product 3 with simultaneous
regeneration of the palladium(0) catalyst.
Conclusion
In summary, we have developed for the first time the
palladium(II)-catalyzed carbonylation of aryl iodides and
aromatic amine derivatives with CO as the suitable start-
ing material. The transformation features high efciency,
atom economy, and broad substrate scope. The obtained
bidentate amide directing groups can be applied as ver-
satile intermediates for various useful transformations.
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Transition Metal Chemistry
Scheme 5 Proposed reaction
mechanism
5. Chen Z, Wang B, Zhang J, Yu W, Liu Z, Zhang Y (2015) Org
Chem Front 2:1107
Further studies to illuminate the reaction mechanism and
extend the application of this methodology are ongoing in
our laboratory.
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Acknowledgements We are grateful to the Key Science Research of
Education Committee in Henan Province (19A150035), the Key Scien-
tifc and Technological Project of Henan Province (192102110222), the
Program for Science & Technology Innovation Talents in Universities
of Henan Province (14HASTIT016) and the Program of Science and
Technology Innovation Talents of Henan Province (No. 2018JQ0011).
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