In situ generated cationic Pd(II)/bipyridine-catalyzed addition of arylboronic acids to N-sulfonyl-arylaldimines

Article abstract of DOI:10.1016/j.tetlet.2017.04.035

An in situ generated cationic Pd(II)/bipyridine-catalyzed nucleophilic addition of arylboronic acids to N-sulfonyl arylaldimines was developed and optimized, and the reaction was proceeded highly efficiently and conveniently in CH₃NO₂

Full text of DOI:10.1016/j.tetlet.2017.04.035

Accepted Manuscript
In-Situ Generated Cationic Pd(II)/Bipyridine-Catalyzed Addition of Arylbor-
onic Acids to N-Sulfonyl-Arylaldimines
Zhenyu Yang, Yuxin Ni, Rui Liu, Kaixuan Song, Shaohui Lin, Qinmin Pan
PII:
S0040-4039(17)30466-5
DOI:
http://dx.doi.org/10.1016/j.tetlet.2017.04.035
TETL 48827
Reference:
Tetrahedron Letters
To appear in:
Received Date:
Revised Date:
Accepted Date:
15 January 2017
5 April 2017
8 April 2017
Please cite this article as: Yang, Z., Ni, Y., Liu, R., Song, K., Lin, S., Pan, Q., In-Situ Generated Cationic Pd(II)/
Bipyridine-Catalyzed Addition of Arylboronic Acids to N-Sulfonyl-Arylaldimines, Tetrahedron Letters (2017), doi:
http://dx.doi.org/10.1016/j.tetlet.2017.04.035
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Tetrahedron Letters
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In-Situ Generated Cationic Pd(II)/Bipyridine-Catalyzed Addition of Arylboronic
Acids to N-Sulfonyl-Arylaldimines
Zhenyu Yang, Yuxin Ni, Rui Liu, Kaixuan Song, Shaohui Lin∗ and Qinmin Pan∗
State and Local Joint Engineering Laboratory for Novel Functional Polymeric Materials, Jiangsu Key Laboratory of Advanced Functional Polymer Design and
Application, Key Laboratory of Organic Synthesis of Jiangsu Province, Green Polymer and Catalysis Technology Laboratory (GAPCT), College of Chemistry,
Chemical Engineering and Materials Science, Soochow University, 199 Ren’ai Road, Suzhou 215123, P. R. China
ARTICLE INFO
ABSTRACT
Article history:
Received
An in-situ generated cationic Pd(II)/bipyridine-catalyzed nucleophilic addition of arylboronic
acids to N-sulfonyl arylaldimines was developed and optimized, and the reaction was proceeded
highly efficiently and conveniently in CH3NO2. A series of arylboronic acids and N-sulfonyl
arylaldimines were surveyed, and 12 of 13 examples gave 90~96% yields.
Received in revised form
Accepted
Available online
2009 Elsevier Ltd. All rights reserved.
Keywords:
Cationic Palladium(II)
Bipyridine
Arylboronic acid
N-Sulfonyl Arylaldimine
Nucleophilic addition
Transition metal catalyzed nucleophilic addition is universal
in carbon backbones construction.1 Hayashi’s group developed a
series of Rh(I)-catalyzed conjugate addition of organoboron
reagents to different α,β-unsaturated compounds,2 and
nucleophilic addition to ketimines,3 N-substituted aldimines,4 in
which excellent asymmetrical inductions had been achieved.
Compared with the expensive rhodium catalysts, palladium
compounds are more economical but rarely investigated in the
nucleophilic addition of arylboronic acids. Uemura5a and
Miyaura5b-e started Pd-catalyzed conjugate addition of
organoboron reagents to enones and enals, and in Miyaura’s
research, cationic Pd(II) complexes with biphosphine ligands
were used as highly reactive catalysts. Compared with neutral
Pd(II) species, cationic Pd(II) has very weak and non-
coordinating counter anions, and this coordination vacancy
favors the transmetallation and alkenes insertion.6 Cationic Pd(II)
catalysts were extensively used in the copolymerization of
alkenes,6b,7 C-H activations8 and other C-C bond formations.9
this nucleophilic addition reactions, and all carbon quaternary
carbon centers can be constructed with this method.10b Then
several groups studied imine type substrates with this
nucleophilic addition strategy,11 and Lu reported a Pd(II)/bpy-
catalyzed addition of arylboronic acids to N-tosylaldimines
(Scheme 1) with 4,4'-dinitro-[2,2']-bipyridine as the best ligand.12
This neutral Pd(OAc)2 catalyzed reaction gave modest to good
yields at high temperature with a prolonged reaction time. Now
we reinvestigated this reaction with our cationic Pd(II) catalysis
strategy, and a highly efficient and mild reaction system was
achieved to realize the nucleophilic addition to imines under
base-free conditions.
Ts
Ts
Ph
N
cat. Pd(OAc)2/bpy HN
1,4-dioxane
PhB(OH)2
+
Ph
2a
Ph
1a
3aa
In our systematic survey of Pd(II)-catalysis,10 a series of
Pd(II)/bipyridine(bpy) catalyzed conjugate addition of
arylboronic acids to α,β-unsaturated aldehydes, ketones,
esters,10d,10e and amides had been realized. In 2007, we reported a
highly efficient cationic Pd(II) catalyzed 1,2-addition of
arylboronic acids to aldehyde to produce diarylmethols,10c in
which nitromethane was proved to be an excellent solvent. It’s
Scheme 1
We reproduced the reaction with Pd(OAc)2/bpy as the catalyst
in 1,4-dioxane, and only a 64% yield was obtained at 95 oC after
2 days (Table 1, entry 1), with incomplete imine conversion. As
cationic Pd(II) catalyst A showed higher activity in our
previously reported nucleophilic addition to aldehydes,10c it’s
tested in this model reaction and a little higher yield (70%) was
given (Table 1, entry 2). Temperature tests (Table 1, entries 3-6)
found that cationic Pd(II) is more active than neutral species in
———
∗ Corresponding author. Tel.: +86-512-67060327; fax: +86-512-65880089; e-mail: linshaohui@suda.edu.cn
∗ Corresponding author. Tel.: +86-512-65882062; fax: +86-512-65880089; e-mail: qpan@suda.edu.cn

2
Tetrahedron Letters
o
revealed that 60 C was optimal to give an 82% yield, and no
reaction was observed at room temperature. Palladium metal
N
N
+ 2AgNO3
(II)Cl
Pd
2
o
precipitate was observed at 95 C with cationic Pd(II) catalyst
(Table 1, entry 2). It’s speculated that the 1,4-dioxane solvent
might cause a competing coordination to Pd(II) catalyst, and it
would obstruct the coordination of imine substrates to Pd(II),
which retarded the nucleophilic addition to imines. Since
CH3NO2 has been proved to be a good solvent for cationic Pd(II)
catalyzed nucleophilic addition due to its polarity and low
coordinating ability,10c CH3NO2 was examined and nearly
quantitative yield was obtained (Table 1, entry 7). At the same
time, the reaction was accelerated and finished in 24 h.
Meanwhile, CH3OH and toluene as solvents only provided 56%
and 20% yields (Table 1, entries 8 and 9).
2AgCl
N
N
(II)L
Pd
n
Ar1B(OH)2
I
SO2R
Ar2
HN
Ar1
IV
N
N
II
(II)L
Pd
Ar1
n
H+
At this point, combining cationic Pd(II) catalyst with CH3NO2
as the solvent accelerated the addition of arylboronic acid to N-
tosylbenzaldimine with complete starting materials conversion.
However, the preparation of cationic Pd(II) catalysts was still a
multi-step and low-yielded process. So we tried to synthesize the
cationic Pd(II) in-situ, in which bpy-PdCl2 complex and silver
trifluoromethanesulfonate were mixed in the reaction. To our
surprise, no side reaction was detected and the expected product
was synthesized highly selectively with a 95% yield (Table 1,
entry 10). The much cheaper silver nitrate was also tired in the
reaction to precipitate the chloride anions, and the same high
III
SO2R
N
N
N
Ar2
L (II)
n
Pd
SO2R
Ar2
N
Ar1
Scheme 2. A proposed mechanism of in-situ generated cationic
Pd(II)-catalyzed addition to N-sulfonylarylaldimines.
1
yield was obtained (Table 1, entry 11). H NMR and HRMS
-
analysis revealed that cationic [(bpy)Pd+(µ-OH)]2·(NO3 )2 was
The proposed mechanism of in-situ generated Pd(II)-catalyzed
addition was shown in Scheme 2. The chlorides on bpy-PdCl2
were removed by AgNO3 to generate the cationic Pd(II) species I.
Transmetallation and C=N bonds insertion were accelerated by
cationic Pd(II)’s intrinsic properties of vacant coordination sites
and high Lewis acidity. The protonolysis of intermediate III
produced the addition product IV and regenerated the cationic
Pd(II) catalyst.
generated in the presence of AgNO3. It means the catalyst
activity was maintained by in-situ preparation of cationic Pd(II),
which was more economic by avoiding the waste of rare metal in
the step-wise synthesis. No reaction happened in the absence of
silver salts (Table 1, entry 12).
In-situ preparation of cationic Pd(II) provided a very
convenient way to perform nucleophilic additions of arylboronic
acids to imines. A series of arylboronic acids were examined
under the optimal conditions, and the scope of N-sulfonyl
arylaldimines was surveyed. For the arylboronic acids with
electron donating groups, p-tolyboronic acid and p-
methoxyphenyl-boronic acid, excellent 92% and 95 yields were
obtained (Table 2, entries 2 and 3). For p-chloro and p-fluoro
substituted phenylboronic acids, >90% yields were also given
(Table 2, entries 4 and 5). As for 1-naphthylboronic acid (Table 2,
entry 6), only 62% of the product was isolated after 48 h with
starting materials remained, and it’s proposed that the steric
hindrance of this arylboronic acid caused incomplete conversion.
For 2-naphthylboronic acid with smaller steric hindrance, the
reaction yielded 90% of the addition product (Table 2, entry 7).
In conclusion, an in-situ generated cationic Pd(II) catalyzed
nucleophilic addition of arylboronic acids to N-Sulfonyl-
arylaldimines was developed and optimized. The reaction was
performed smoothly under air and N-Sulfonyl-arylamines were
produced highly efficiently and conveniently. 12 of 13 examples
gave >90% yields, which showed very high tolerance of
functional groups.
Setting phenylboronic acid as the invariable, electron donating
and withdrawing substitutes were introduced into the N-sulfonyl-
arylaldimines (Table 2, entries 8-11), and they all gave perfect
yields in the nucleophilic additions. Even for N-tosyl-p-
nitrobenzaldimine (Table 2, entry 12), 93% of the addition
product was given. Also the N-tosyl group was changed to N-
mesyl group, and a 92% yield was obtained (Table 2, entry 13).
All these results demonstrated that this cationic Pd(II) catalyzed
reaction was insensitive to electronic properties on the aryl
groups on the substrates, and most reactions were finished in 24 h.

Table 1. Pd(II)-bipyridine catalyzed addition of phenylboronic acid to N-tosylbenzaldiminea
Ts
Ts
Cat. Pd(II)
N
HN
Ph
PhB(OH)2
+
Ph
Ph
2+
H
N
N
N
N
O
Pd Pd
-
2CF3SO3
O
H
A
Entry
1
Catalyst
Solvent
Temperature (oC)
95
Time (hrs)
Yield (%)b
64
Pd(OAc)2/bpy
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
CH3NO2
48
48
48
48
48
48
24
48
48
24
24
24
2
3
A
A
A
A
A
A
A
A
95
80
60
40
rt
70
80
82
53
0
4
5
6
7
60
60
60
60
60
60
96
56
20
95
95
0
8
Toluene
9
CH3OH
10
11
12
bpy-PdCl2/2CF3SO3Ag
bpy-PdCl2/2AgNO3
bpy-PdCl2
CH3NO2
CH3NO2
CH3NO2
aReaction conditions: N-tosylbenzaldimine (1.0 mmol), PhB(OH)2 (2.0 mmol), Pd(II) (0.05 mmol). The optimized conditions highlighted in bold.
bIsolated yield.
Table 2. Cationic Pd(II) catalyzed addition of arylboronic acid to N-Sulfonylarylaldiminesa
SO2R
SO2R
HN
Ar1
Cat. bpy-PdCl2/2AgNO3
N
Ar1B(OH)2
+
Ar2
Ar2
CH3NO2, 60 oC
Entry
1
ArB(OH)2
Product
Time (hrs)
Yield (%) b
α,β-Unsaturated amide
Ts
Ts
N
HN
Ph
B(OH)2
24
95
Ph
Ph
1a
2a
3aa
Ts
HN
Ts
N
Me
B(OH)2
2
3
4
24
92
95
92
Ph
1b
2a
Me
MeO
Cl
3ba
Ts
HN
Ts
N
MeO
B(OH)2
24
Ph
1c
2a
3ca
Ts
HN
Ts
N
Cl
B(OH)2
1d
24
Ph
2a
3da

4
Tetrahedron
Ts
Ts
HN
Ts
Ts
Ts
N
F
B(OH)2
1e
5
6
7
8
24
48
24
24
93
62
90
96
Ph
Ph
Ph
2a
F
3ea
B(OH)2
HN
N
2a
1f
3fa
Ts
Ts
HN
B(OH)2
N
1g
2a
3ga
Ts
HN
N
B(OH)2
1a
2b
Me
MeO
Cl
Me
3ba
Ts
Ts
HN
N
B(OH)2
9
24
96
1a
2c
3ca
MeO
Ts
Ts
HN
N
B(OH)2
10
11
12
13
24
24
24
24
95
95
93
92
1a
2d
Cl
3da
Ts
Ts
HN
N
B(OH)2
1a
2e
F
F
3ea
Ts
Ts
HN
N
B(OH)2
1a
2f
O2N
O2N
3af
SO2Me
SO2Me
HN
N
B(OH)2
1a
2g
3ag
aReaction conditions: N-Sulfonylarylaldimines (1.0 mmol), arylboronic acid (2.0 mmol), bpy-PdCl2 (0.05 mmol), AgNO3 (0.10 mmol), CH3NO2 4 mL, 60 oC.
bIsolated yield.

2
Tetrahedron
Acknowledgments
We gratefully acknowledge the National Natural Science Foundation of China, Specialized Research Fund for the Doctoral
Program (SRFDP) of Higher Education (No. 20113201120006), the Priority Academic Program Development (PAPD) of Jiangsu
Higher Education Institutions, Soochow University Funds (Nos. 14109001, Q410900510) and Suzhou Industrial Park Fund for
financial support.
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Supplementary Material
1
Supplementary data (preparation of substrates, typical experimental procedures, characterization of all products, H and 13C
NMR spectra) associated with this article can be found, in the online version, at:

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In-Situ Generated Cationic
Pd(II)/Bipyridine-Catalyzed Addition of
Arylboronic Acids to N-Sulfonyl-
Arylaldimines
Leave this area blank for abstract info.
Zhenyu Yang, Yuxin Ni, Rui Liu, Kaixuan Song, Shaohui Lin* and Qinmin Pan*

Highlights for Manuscript TETL-D-17-00104R1
In-Situ Generated Cationic Pd(II)/Bipyridine-Catalyzed Addition of
Arylboronic Acids to N-Sulfonyl-Arylaldimines
Zhenyu Yang, Yuxin Ni, Rui Liu, Kaixuan Song, Shaohui Lin* and Qinmin Pan*
State and Local Joint Engineering Laboratory for Novel Functional Polymeric Materials, Jiangsu Key Laboratory of Advanced
Functional Polymer Design and Application, Key Laboratory of Organic Synthesis of Jiangsu Province, Green Polymer and
Catalysis Technology Laboratory (GAPCT), College of Chemistry, Chemical Engineering and Materials Science, Soochow
University, 199 Ren’ai Road, Suzhou 215123, P. R. China
e-mail: linshaohui@suda.edu.cn
1. Highly reactive cationic Pd(II)-bpy was in-situ generated in CH3NO2.
2. High yielded Pd(II)-catalytic addition to arylaldimines was optimized.
3. Air and moisture insensitive Pd(II)-catalysis was developed.
4. 12 of 13 examples yielded >90% and showed high functional groups tolerance.