N-heterocyclic carbene palladium(II)-catalyzed Suzuki-Miyaura cross coupling of N-acylsuccinimides by C-N cleavage

Article abstract of DOI:10.1016/j.jorganchem.2018.09.026

An easily prepared, well-defined N-heterocyclic carbene-palladium(II) complex was found to be an efficient catalyst for the Suzuki-Miyaura cross-coupling of N-acylsuccinimides with arylboronic acids via C-N bond activation. Under the optimal conditions, a

Full text of DOI:10.1016/j.jorganchem.2018.09.026

Accepted Manuscript
N-heterocyclic carbene palladium(II)-catalyzed Suzuki-Miyaura cross coupling of N-
acylsuccinimides by C-N cleavage
Tao Wang, Jiarui Guo, Hengjin Wang, Han Guo, Dingli Jia, Wen Zhang, Lantao Liu
PII:
S0022-328X(18)30731-9
10.1016/j.jorganchem.2018.09.026
JOM 20583
DOI:
Reference:
To appear in: Journal of Organometallic Chemistry
Received Date: 23 August 2018
Revised Date: 24 September 2018
Accepted Date: 25 September 2018
Please cite this article as: T. Wang, J. Guo, H. Wang, H. Guo, D. Jia, W. Zhang, L. Liu, N-heterocyclic
carbene palladium(II)-catalyzed Suzuki-Miyaura cross coupling of N-acylsuccinimides by C-N cleavage,
Journal of Organometallic Chemistry (2018), doi: https://doi.org/10.1016/j.jorganchem.2018.09.026.
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ACCEPTED MANUSCRIPT

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N-heterocyclic carbene palladium(II)-catalyzed Suzuki-Miyaura
Cross Coupling of N-Acylsuccinimides by C-N Cleavage
*
*
Tao Wang , Jiarui Guo, Hengjin Wang, Han Guo, Dingli Jia, Wen Zhang, Lantao Liu
Henan Engineering Laboratory of Green Synthesis for Pharmaceuticals, School of
Chemistry and Chemical Engineering, Shangqiu Normal University,
Shangqiu, Henan, 476000, People’s Republic of China
Henan Key Laboratory of Biomolecular Recognition and Sensing, School of
Chemistry and Chemical Engineering, Shangqiu Normal University,
Shangqiu, Henan, 476000, People’s Republic of China
ABSTRACT: An easily prepared, well-defined N-heterocyclic carbene-palladium(II)
complex was found to be an efficient catalyst for the Suzuki-Miyaura cross-coupling
of N-acylsuccinimides with arylboronic acids via C-N bond activation. Under the
optimal conditions, all reactions proceeded smoothly generating broad array of diaryl
ketones in good to high yields (81->99%) within hours.
Introduction
Functional molecules containing arylketone skeletons are of considerable interest
[
1]
[2]
since there are widely existed in compounds of natural products, pharmaceuticals
*
Tel./Fax: +86 0370-2595126; e-mail: wt67751726@126.com or liult05@iccas.ac.cn .

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[
3]
and act as key intermediates in synthetic chemistry. Recently, intense efforts have
been made for the development of various methods to access structurally diverse
[
4]
families of substituted arylketone derivatives. Among them, transition metal
catalyzed acylative Suzuki coupling is one of the most important and frequently used
methods to synthesize arylketones. Over the past decade, strategies for the cross
[
5]
[6]
[7]
coupling of unactivated acyl chlorides, anhydrides and esters using Ni and
Pd-catalysis have been reported. However, there have been far fewer reports on
[
8]
acylative Suzuki coupling of amides . One obvious reason for the cross-coupling of
unactivated amides is slow oxidative addition of the C(acyl)-N bond to the metal. In
2
017, Szostak described the first use of versatile PEPPSI type of Pd-NHC complexes
[
9]
as catalysts for the cross-coupling of amides by C-N bond activation. Inspired by
this breakthrough, the same group realized Suzuki-Miyaura cross-coupling of amides
and esters by selective C(acyl)-N and C(acyl)-O cleavage at room temperature with
[
10]
Hazari's (η3-1-t-Bu-indenyl)Pd(IPr)(Cl) complexes as pre-catalysts.
Meanwhile,
the first method for the direct activation of N-methylamino pyrimidyl amides (MAPA)
[
11]
by selective C-N amide bond cleavage has also been developed.
Despite the
impressive progress made so far in the Suzuki-Miyaura cross-coupling of amides, the
development of practical methods by selective C(acyl)-N scission in amides remains
an elusive goal in organic synthesis. In our previous work, we reported a simple route
[
12]
[13]
to the synthesis of a series of mononuclear,
dinuclear
with bridging N-heterocyclic ligands. These
NHC-palladium(II) complexes proved to be effective catalyst precursors for the
and trinuclear
[
14]
NHC-palladium(II) complexes

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Suzuki-Miyaura coupling of both aryl and benzyl chlorides with arylboronic acids.
Encouraged by these results, we have extended our investigations of the catalytic
potential of these complexes. Herein, we report their application in the
Suzuki-Miyaura cross-coupling of N-acylsuccinimides with arylboronic acids
(Scheme 1).
Scheme 1. NHC-Pd(II) catalyzed acylative Suzuki coupling of amides.
Results and discussion
Initially, 1-benzoylpyrrolidine-2,5-dione 1a and phenylboronic acid 2a were chosen
as model substrates to optimize the reaction conditions. The details were shown in
Table 1. The choice of base is crucial to the yield of the reaction (Table 1, entries
[
15]
1
-12) . To our delight, in the presence of the N-heterocyclic carbene-palladium(II)
o
complex 4a as the catalyst, Na CO as the base in toluene at 80 C, the reaction gave
2
3
the corresponding benzophenone in 85% yield. Several other solvents including THF,
i
PrOH and 1,4-dioxane were tested, and the yield was not enhanced further (Table 1,
entries 13-15). Then the performance of the other six NHC-Pd(II) complexes 4b-g in
this reaction was examined. It was found that the coordination environment of the
NHC-Pd(II) complexes had an obvious effect on the yield (Table 1, entries 16-21).
And complex 4c was found to be the most appropriate, giving the benzophenone in
9
6% yield (entry 17).

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Table 1 Optimization of reaction conditions for Suzuki-Miyaura reaction of
1
-benzoylpyrrolidine-2,5-dione with phenylboronic acid catalyzed by the NHC-Pd(II)
a
complexes
b
Entry
Cat.
4a
4a
4a
4a
4a
4a
4a
4a
4a
4a
4a
4a
4a
4a
Base
Solvent
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
THF
Yield (%)
trace
trace
26
t
1
2
3
4
5
6
7
8
9
KO Bu
t
NaO Bu
Cs CO
2
3
Na CO
85
2
3
K CO
2
58
3
Li CO
22
2
3
NaHCO3
K PO
trace
24
3
4
KH PO
trace
trace
78
2
4
1
0
1
NaOAc
NaOH
KOH
1
12
13
14
34
Na CO
80
2
3
Na CO
1,4-dioxane
71
2
3

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i
15
16
17
18
19
20
21
4a
4b
4c
4d
4e
4f
Na CO
PrOH
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
22
41
96
51
34
51
42
2
3
3
3
3
3
3
3
Na CO
2
Na CO
2
Na CO
2
Na CO
2
Na CO
2
4g
Na CO
2
a
All reactions were carried out using 1a (0.20 mmol), 2a (0.60 mmol), base (2.0
o
b
equiv), Cat. (3.0 mol%) in solvent (1.0 mL) at 80 C for 16 h. Isolated yields.
With the optimized conditions in hand, we turned toward testing the substrate scope
of aromatic boronic acids (Table 2). Gratifyingly, most of the coupling reaction
proceeded rapidly and efficiently to provide the corresponding diaryl ketones in
excellent yields. Both electron-donating and electron-withdrawing groups in the
phenyl ring of aryl boronic acids were tolerated and good results were obtained
(3aa-3aj). Roughly, the electron-donating group in the phenyl ring of aryl boronic
acids (3aa-3ah) showed some beneficial effect on the yields of the catalysis products.
In general, ortho-, para-, and meta-substituted aryl boronic acids exhibited similar
reactivities in this catalytic system (3ae-3ag). The aryl boronic acids bearing halide
substituent (3ai) was also both tolerated in this transformation. In addition, in the case
of 1-naphthylboronic acid afforded in high reaction efficiency under the present
reaction conditions (3ak). Heteroaromatic boronic acid, such as thienyl, was well
transformed to corresponding product with moderate yield (3al).

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a
Table 2 Scope of arylboronic acids
O
O
O
O
3aa (96%)
3ab (96%)
3ac (95%)
3ad(94%)
O
O
O
O
OCH3
OCH3
OCH3
OCH3
OCH3
3ae (>99%)
3af (99%)
3ag (98%)
3
ah (96%)
O
O
O
O
S
CF3
F
3ai (98%)
3aj (87%)
3ak (95%)
3al (81%)
a
All reactions were carried out using 1a (0.20 mmol), 2 (0.60 mmol), Na CO (2.0
2
3
o
equiv), Cat. 4c (3.0 mol%) in toluene (1.0 mL) at 80 C for 16 h.
Inspired by these results and our attention was next turned to the cross coupling
reaction of aromatic amides with phenyl boronic acids. As shown in Table 3, the
reactions proceed smoothly to afford diaryl ketones in excellent yields. Particularly,
when electron-deficient amides such as N-(4-trifluoromethylbenzoyl)succimide was
used as the substrate, excellent yield of the corresponding product was observed (98%
yield, 3bg). Amides bearing fluorine substituent showed good reactivity in this
transformation (98% yield, 3bf). Thienyl amide was tolerated in this reaction and
provided the diaryl ketones with high reaction efficiency (87% yield, 3bh). The above

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results confirm that the NHC-Pd(II) complexes are really effective catalysts for the
Suzuki-Miyaura reaction.
a
Table 3 Scope of amide coupling partner
a
All reactions were carried out using 1 (0.20 mmol), 2a (0.60 mmol), Na CO (2.0
2
3
o
equiv), Cat. 4c (3.0 mol%) in toluene (1.0 mL) at 80 C for 16 h.
Conclusion
In summary, we reported NHC-Pd(II) catalyzed Suzuki-Miyaura cross-coupling of
N-acylsuccinimides to form diaryl ketones, a very important skeleton in synthetic
chemistry. This reaction features modular, easily prepared NHC-Pd(II) precatalysts,
which can be used under operationally convenient conditions. More importantly, this
report shows broad scope with respect to both the boronic acid and amide components.
Further exploration of these N-heterocyclic carbene-palladium(II) complexes and their
catalytic applications in other reactions is in progress.

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Experimental
General Remarks
The catalytic reactions were carried out under a nitrogen atmosphere.
[
16]
N-benzoylsuccinimides was prepared according to the literature method . Solvents
were dried by standard methods and freshly distilled prior to use. All other chemicals
1
13
were used as purchased. H and C NMR spectra were recorded on a Bruker DPX
00 instrument using TMS as an internal standard.
General Procedure for the Suzuki-Miyaura
N-benzoylsuccinimides.
4
Cross-Coupling
of
A Schlenk flask was charged with the required N-benzoylsuccinimides (0.20 mmol),
aryl boric acid (0.60 mmol), N-heterocyclic carbene-palladium(II) complex (3 mol %),
o
Na CO (2.0 equiv), and toluene (1.0 mL). The mixture was stirred at 80 C for 16 h
2
3
under N . After cooling, the mixture was evaporated and the product was isolated by
2
preparative TLC on silica gel plates. The purified products were identified by NMR
spectra and their analytical data are given in the Supporting Information.
Acknowledgments
We gratefully acknowledge financial support from the National Natural Science
Foundation of China (Nos. U1404205, 21572126), the Key Science Research of
Education Committee in Henan Province (19A150035) and the Program of Science
and Technology Innovation Talents of Henan Province (2018JQ0011).
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Highlights
.
The Suzuki-Miyaura cross-coupling of N-acylsuccinimides with arylboronic acids
has been developed.
.
.
Broad array of diaryl ketones have been prepared.
The N-heterocyclic carbene-palladium(II) complex showed good catalytic activity
in this reaction.