Denitrogenative Pd/Cu-catalyzed Suzuki-type Cross-coupling of Aryltrifluoroborates with Arylhydrazine Hydrochlorides in Water under Room Temperature

Article abstract of DOI:10.1002/aoc.4203

A water-soluble palladium-catalyzed Suzuki-type cross-coupling of aryltrifluoroborates with arylhydrazide hydrochlorides was efficiently developed under mild and environmentally benign conditions, in water without any ligand. The newly developed Pd/Cu co-catalyzed denitrogenative reaction gave a range of structurally diverse substituted biaryls with good to excellent yields, in which the byproduct was nitrogen.

Full text of DOI:10.1002/aoc.4203

Received: 4 October 2017
DOI: 10.1002/aoc.4203
Revised: 27 October 2017
Accepted: 30 October 2017
C O M M U N I C A T I O N
Denitrogenative Pd/Cu‐catalyzed Suzuki‐type Cross‐
coupling of Aryltrifluoroborates with Arylhydrazine
Hydrochlorides in Water under Room Temperature
1
1
1
1,2
1
Guofang Wang | Mengting Meng | Liping Deng | Kai Cheng
| Chenze Qi
1
Zhejiang Key Laboratory of Alternative
A
water‐soluble palladium‐catalyzed Suzuki‐type cross‐coupling of
Technologies for Fine Chemicals Process,
Shaoxing University, 312000 Shaoxing,
People's Republic of China
aryltrifluoroborates with arylhydrazide hydrochlorides was efficiently devel-
oped under mild and environmentally benign conditions, in water without
any ligand. The newly developed Pd/Cu co‐catalyzed denitrogenative reaction
gave a range of structurally diverse substituted biaryls with good to excellent
yields, in which the byproduct was nitrogen.
2
Organisch‐Chemisches Institut,
Universität Heidelberg, Im Neuenheimer
Feld, 270 69120 Heidelberg, Germany
Correspondence
Kai Cheng and Chenze Qi, Zhejiang Key
Laboratory of Alternative Technologies for
Fine Chemicals Process, Shaoxing
University, 312000 Shaoxing People's
Republic of China.
KEYWORDS
arylhydrazide hydrochlorides, aryltrifluoroborates, Suzuki‐type cross‐coupling, water, water‐soluble
Pd‐catalyzed
Email: chengkai@usx.edu.cn;
qichenze@163.com
[8–14]
1
| INTRODUCTION
friendlier than most other available organometallics.
Moreover, organoboron reagents such as boronic
acids exhibit moisture, air, and heat stability, thus
allowing cross‐couplings to be performed under
convenient reaction conditions. Organoboronic acids are
hard to determinate the precise stoichiometry because
the existence of dimeric and trimeric anhydrides with loss
of water. Otherwise, organoboronic acids are easier to
give deboronation and homocoupling by‐products, and
sensitive to many commonly used reagents in organic
synthesis.
Transition‐metal‐catalyzed cross‐coupling reactions have
made a great contribution to the recent growth of organic
synthesis. A great diversity of carbon‐carbon/heteroatom
bonds can now be easily generated by transition‐
metal‐catalyzed protocols that find wide applications in
the synthesis of substances such as natural products,
[
1,2]
agrochemicals, materials, dyes, and pharmaceuticals.
From a ‘green and sustainable chemistry’ perspective,
water is a particularly environmentally safe and attractive
alternative solvent in synthetic chemistry. Water, as a
hydrogen source, is undoubtedly one of the most
suitable and promising routes for constructing com-
Boronic acids and boronate esters can be replaced
effectively by the corresponding organotrifluoroborates in
transmetallation reactions, rendering many advantages
over the former. Trifluoroborates are increasingly important
reagents because of their favorable physical and chemical
properties; additionally, they offer an alternative to toxic
pounds. Water is
a renewable resource that is
nontoxic, nonflammable, and cost‐effective. The primary
motivations to carry out cross‐coupling reactions in aque-
[
3–7]
[15–19]
ous solvents have been economic and environmental.
organometallic species such as organostannanes.
The Suzuki−Miyaura reaction, among all cross‐coupling
reactions, is especially important because one of the
coupling partners, the organoboron counterpart, is
generally more readily available and environmentally
The tetracoordinate nature of the trifluoroborates
makes them resistant to a variety of reaction conditions.
This characteristic allows one to build complexity into a
molecule while leaving the carbon−boron bond intact.
Appl Organometal Chem. 2017;e4203.
wileyonlinelibrary.com/journal/aoc
Copyright © 2017 John Wiley & Sons, Ltd.
1 of 9
https://doi.org/10.1002/aoc.4203

2
of 9
WANG ET AL.
Traditionally, aryl halides are most widely used electro-
which is utilized as an effective arylation partner in
[
43–50]
philic reagents in Pd‐catalyzed Suzuki‐type cross‐coupling
reactions with organotrifluoroborates (Scheme 1, C–X
oxidative radical arylation
and Pd‐catalyzed cross‐
Suzuki‐type,
[
51–54]
[55–58]
coupling (Heck‐type,
addi-
etc.[64–73]) via C—N bond
cleavage. In continuation of our interest in Pd‐catalyzed
[20–23]
[59,60]
[61–63]
bond).
Subsequently, the methods utilizing aryl ester
tion,
homocoupling,
which derived from the respective phenols in Suzuki‐type
coupling with organotrifluoroborates have been devel-
oped. The transformation proceeded via C–O bond
[
34,36,59]
denitrogenative cross‐coupling reactions,
we
report a novel and efficient Pd‐catalyzed denitrogenative
Suzuki‐type coupling of aryltrifluoroborates with
arylhydrazine hydrochlorides under room temperature.
[
24–26]
cleavage instead of C–X bond with aryl tosylates,
aryl
[27]
[28,29]
sulfamates
and aryl mesylates
(Scheme 1, C‐O
bond). Decarboxylative Suzuki‐type cross‐coupling was
reported by Liu et al. using stable carboxylic acids as
substrates and give access to various valuable product
2 | RESULTS AND DISCUSSION
[
30]
through the removal of CO . (Scheme 1, C‐C bond).
2
Compared with C‐Br/C‐I bond, C‐N bond is a rela-
tively inert chemical bond with shorter bond length and
is less susceptible to polarity. In the past decades, the acti-
vation of the C(sp )–N bond has become flourishing to
afford biaryl derivatives which are recognized as funda-
Considered that the infusibility of both arylhydrazine
hydrochlorides and aryltrifluoroborate in organic solvent,
water could be much better medium candidate for this
transformation. Our initial attempt started with the reac-
tion of p‐tolylhydrazine hydrochloride and potassium
phenyltrifluoroborate catalyzed with 1 mol% Pd(OAc)2
and 2 mol% CuCl •2H O in water at 25 °C, but the reac-
2
mental structuralmotifs in myriads of pharmaceuticals,
[31,32]
natural products and agrochemicals.
Suzuki–type
2
2
cross‐coupling with organotrifluoroborates through the
cleavage of C–N bond providing another alternative for
electrophilic reagents (Scheme 1, C‐N bond). The
arenediazonium salts have been applied as electrophilic
partners in Pd‐catalyzed Suzuki‐type coupling with
tion did not occur. We were delighted by the results that
the reaction could take place with a low yield using
K CO (2.0 eq.) as a base in water (Table 1, entry 1).
2
3
Attracted by this denitrogenative cross‐coupling reaction
promoted by the base, efforts were then made to improve
the yield of this direct Suzuki‐type coupling reaction.
Although many traditional Pd(0) and Pd(II) catalysts have
been tested, no better results were obtained (Table 1,
entries 2–6). We envisaged that the poor solubility of Pd
catalysts in water could inhabit this intended transforma-
tion. Hydrosoluble palladium salts, such as Pd(OH)2,
Na PdCl Na PdBr K PdCl and K PdBr were tested,
organotrifluoroborates via the release of N under mild
2
[33–36]
conditions for a long time.
Schmidt et al. reported
a Pd‐catalyzed Suzuki‐type deacetylation–diazotation–
[
37]
coupling with acetanilides as formal leaving groups.
2
As a special synthons containing C(sp )‐N bond,
[
38–42]
arylhydrazines are used as organic synthesis blocks
due to their low cost, high reactivity and easy availability,
has attracted a growing interest of chemists due to its ver-
satility by denitrogenation via transition‐metal catalyzed
C–N activation. In cross‐coupling arylation. Recent
advances in the coupling reactions of arylhydrazine,
2
4,
2
4,
2
4
2
4
and to our delight, treatment of phenyltrifluoroborate
with p‐tolylhydrazine hydrochloride in water with
hydrosoluble palladium salts in moderate yields
(Table 1, entries 7–11). The yield was found to be
SCHEME 1 Pd‐catalyzed Suzuki‐type
coupling of aryltrifluoroborates

WANG ET AL.
3 of 9
a
TABLE 1 Influence of the catalysts in cross‐coupling of p‐tolylhydrazine hydrochloride with potassium phenyltrifluoroborate
catalyst
.
CuCl2 2H2O
BF3K
H3C
NHNH2 HCl
CH3
K2CO3
H2O, RT
b
b
Entry
Catalyst
Pd(OAc)
PdCl
Pd(PhCN)
Pd(CH CN)
PdCl (PPh
Pd(PPh
Pd(OH)
Yield (%)
Entry
Catalyst
Yield (%)
1
2
16
12
15
10
8
11
K
2
2
PdBr
4
54
.
2
3
4
5
6
7
8
9
2
12
13
14
15
16
17
18
19
20
K
Pd(CN)
4
3H
2
O
67
90
87
94
82
80
85
34
29
2
Cl
2
Pd(NH
Pd(NH
Pd(NH
Pd(NH
Pd(NH
Pd(NH
3
3
3
4
4
2
)
)
)
)
)
4
4
2
2
4
Cl
2
3
2
Cl
2
Br
2
2
3
)
3
Cl
Cl
Cl
2
4
6
3
)
4
11
49
55
51
57
2
Na
Na
2
2
PdCl
4
2 2 2
NH ) Cl
PdBr
4
K
2
PdCl
6
1
0
K
2
PdCl
4
(NH PdCl
4
)
2
6
a
.
Reaction conditions: phenyl trifluoroborate (0.6 mmol), 4‐methyl phenylhydrazine hydrochloride (0.5 mmol), catalyst (1 mol%), CuCl
1.mmol), H O (1.0 ml) at 25 °C for 12 hours unless otherwise indicated.
Isolated coupling yield.
2 2 2 3
2H O (2 mol%), K CO
(
b
2
increased up to 67% (Table 1, entry 12) with
no result (Table 2, entries 11–12). Furthermore, the base
also plays an important role in the transmetallation of the
aryl trifluoroborate. In the absence of a base, low yield of
diaryl product was observed (Table 2, entry 13). To investi-
gate the importance of bases for the Suzuki‐type coupling,
we replaced K CO with other bases, such as NaHCO ,
.
K Pd(CN) 3H O, so we envisioned that nitrogen chelation
2
4
2
palladium‐catalysts might be utilized for the cleavage of
carbon–nitrogen bonds and hence the important variable
to be optimized in the denitrogenative cross‐coupling pro-
cess. So, different palladium ammonia complex viz.
Pd(NH ) Cl Pd(NH ) Br and Pd(NH ) Cl were tested
2
3
3
Na CO , Cs CO or (NH ) CO , under identical condi-
3
4
2,
3 4
2
3 2
2
2
3
2
3
4 2
3
to determine their catalytic efficacy (Table 1, entries 13–
5). Exceedingly high product yield (94%) was obtained
in the presence of Pd(NH ) Cl (Table 1, entry 15).
tions, and comparable conversion was observed (Table 2,
entries 14–17). While a moderate yield was obtained
with t‐BuOK, K PO , NaOAc and KOAc (Table 2, entries
1
3
2
2
3
4
Pd(NH ) Cl and Pd(NH ) Cl and Pd(NH NH ) Cl were
18–21), K CO was proved to be the best oxidant. however,
4
2
4
4 4
6
2
2 2
2
2
3
also screened (Table 1, entries 16–18), but none of them
addition of bases such as CsF, NaOH, and Et N did not
3
was found to be superior. The formation of the desired
improve the yield in this work (Table 2, entries 22–24).
product halted with Pd(IV) catalysts, such as K PdCl6
The appropriate amount of K CO was 2.0 equiv. and no
2
2
3
and (NH ) PdCl (Table 1, entries 19–20). Obviously, palla-
significant increased yield of 4‐methylbiphenyl was
4
2
6
dium ammonia catalyst plays a pivotal role in the catalytic
cycle. A lower yield was obtained when we further
decreased the catalyst loading to 0.5 mol%.
observed with more than 2.0 equiv. of K CO . It is worth
noting that a moderate yield could be achieved when the
amount of base was decreased to 1.0 equiv.
2
3
When a control experiment was proceeded in the
On the basis of the screening of the above Pd‐
catalyzed cross‐coupling reaction conditions, it can be con-
cluded that the optimized reaction should be performed in
the presence of 1 mol% Pd(NH ) Cl , 2 mol% CuCl •2H O,
absence of CuCl •2H O, No desired cross‐coupling prod-
2
2
uct was found (Table 1, entry 1). Next, several Cu(II) and
Cu(I) salts were screened for this coupling reaction. Com-
parison of different copper sources indicated that
CuCl •2H O was superior to the other copper(II) sources
3
2
2
2
2
and K CO in H O at room temperature for 12 h. With the
2
3
2
optimized reaction conditions established, various sub-
strates were subjected to cross‐coupling reactions, and rep-
resentative results are described in Table 3. First,
phenylhydrazine hydrochloride was fixed as the substrate
to test various substituted potassium aryltrifluoroborates
derivatives. It was found that different potassium
aryltrifluoroborates derivatives could undergo the cross‐
coupling reaction smoothly to afford the corresponding
2
2
such as CuBr , Cu(OAc) •H O, Cu(OTf) and Cu(TFA)
2
2
2
2
2
(
Table 2, entries 2–6). Indeed, only modest yield was
obtained when CuSO •5H O and Cu(NO ) •3H O were
4
2
3 2
2
tested as reaction promotor (Table 2, entries 7–8). In addi-
tion, it was obvious that copper(I) source was inferior to
copper(II) source under the same conditions (Table 2,
entries 9–10). It was found that AgOAc and K S O gave
2
2 8

4
of 9
WANG ET AL.
TABLE 2 Influence of the co‐catalysts and bases in cross‐coupling of p‐tolylhydrazine hydrochloride with potassium phenyltrifluoroborate
Pd(NH3)2Cl2
co-catalyst
BF3K
H3C
NHNH2 HCl
CH3
base
H2O, RT
b
b
Entry
Co‐catalyst
Base
Yield (%)
Entry
Co‐catalyst
Base
Yield (%)
.
1
‐
K
2
K
2
K
2
K
2
K
2
K
2
K
2
K
2
K
2
K
2
K
2
K
2
CO
CO
CO
CO
CO
CO
CO
CO
CO
CO
CO
CO
3
3
3
3
3
3
3
3
3
3
3
3
‐
13
14
15
16
17
18
19
20
21
22
23
24
CuCl
CuCl
CuCl
CuCl
CuCl
CuCl
CuCl
CuCl
CuCl
CuCl
CuCl
CuCl
2
2
2
2
2
2
2
2
2
2
2
2
2H
2H
2H
2H
2H
2H
2H
2H
2H
2H
2H
2H
2
2
2
2
2
2
2
2
2
2
2
2
O
O
O
O
O
O
O
O
O
O
O
O
‐
14
.
.
.
.
.
.
.
.
.
.
.
.
2
3
4
5
6
7
8
9
CuCl
CuBr
Cu(OAc)
2
2H
2
O
94
86
82
84
77
62
58
22
15
‐
NaHCO
3
81
87
76
70
65
67
58
62
30
22
14
2
Na
Cs
(NH
t‐BuOK
PO
2
CO
3
.
2
2
H
2
O
2
CO
3
Cu(OTf)
2
4
)
2
CO
3
Cu(TFA)
.
CuSO
4
5H
2
O
K
3
4
.
Cu(NO
CuCl
CuI
3
)
2
3H
2
O
NaOAc
KOAc
CsF
1
1
1
0
1
2
AgOAc
NaOH
K
2
S
2
O
8
‐
3
Et N
a
Reaction conditions: potassium phenyltrifluoroborate (0.6 mmol), 4‐methyl phenylhydrazine hydrochloride (0.5 mmol), Pd(NH
2 mol%), base (1.mmol), H O (1.0 ml) at 25 °C for 12 hours unless otherwise indicated.
3
)
2
Cl
2
(1 mol%), co‐catalyst
(
2
b
Isolated coupling yield.
biaryls in good yields. Denitrogenative Pd/Cu‐catalyzed
Suzuki‐type coupling was observed using the para‐
substituted electron‐donating and electron‐withdrawing
aryltrifluoroborates derivatives, MeOPhBF K, MePhBF K,
1H‐indol‐5‐yltrifluoroborate were employed in the
reaction (Table 3, entries 18‐23).
Subsequently, various arylhydrazine hydrochlorides
were also tested under the standard reaction conditions.
The results indicated that the reaction could be success-
fully extended to arylhydrazine hydrochlorides under
3
3
CNPhBF K, NO PhBF K, CF PhBF K, resulting in 81–
3
2
3
3
3
9
1% yields of the desired products (Table 3, entries 1‐5).
Moreover, meta‐ or ortho‐substituent groups (Me, NO2)
on the benzene ring remained unaffected under these reac-
tion conditions and afforded the corresponding products in
good yields (Table 3, entries 6‐9). Excitingly, the results
indicated that Cl, Br, and I substituted on the phenyl ring
were also well‐tolerated under optimized conditions and
led to a beneficial effect on the reaction outcome, which
made further functionalization possible (Table 3, entries
the optimum conditions, and a broad range of
arylhydrazine hydrochlorides were converted into corre-
sponding biaryls in good to excellent yields (Table 3,
entries 24‐46). Under the optimized reaction conditions,
arylhydrazine hydrochlorides with diverse electron‐
donating and electron‐withdrawing substituents (MeO, t‐
Bu, CN, F, Cl, NO and CF ) underwent highly efficient
2
3
cross‐coupling reactions (Table 3, entries 24‐31). Notably,
substrates containing Ac and COOMe groups underwent
cross‐coupling (Table 3, entries 32‐33). In most cases,
meta‐ or ortho‐substituted aryltrifluoroborates derivatives
1
0‐12). Different substituents on the phenyl ring, such as
COOMe and NMe , also led to a beneficial effect on the
2
reaction outcome (Table 3, entries 13‐14). Hydroxy
substituents on the benzene ring was also toleranted,
although with a reduced yield (Table 3, entry 15).
Desired product was formed when the reaction was
carried out using potassium benzo[d][1,3]dioxol‐5‐
yltrifluoroborate or potassium (E)‐styryltrifluoroborate,
respectively, as the substrate (Table 3, entries 16‐17).
Notably, denitrogenative coupling products were also
obtained in moderate to good yields, when the heterocyclic
with groups (MeO, CN, CF ) at the benzene ring
3
reacted smoothly and afforded the corresponding
products in 71–85% yields (Table 3, entries 34‐39). 3,4‐
Dimethylphenylhydrazine hydrochlorides was employed
to explore the scope of this transformation, the target
product was also obtained in good yield (Table 3, entry 40).
Notably, the desired product was formed when the reac-
tion was carried out using strongly electron‐withdrawing
substituted substrates (Table 3, entry 41). Naphthyl‐
substituted hydrazine hydrochlorides could also be
employed in this reaction to afford the products in good
substrates
thiophen‐2‐yltrifluoroborate,
thiophen‐3‐
yltrifluoroborate, furan‐3‐yltrifluoroborate, benzofuran‐2‐
yltrifluoroborate, 1H‐pyrazol‐4‐yltrifluoroborate and

WANG ET AL.
5 of 9
a
TABLE 3 Cross‐coupling of various aryl trifluoroborate with various arylhydrazine hydrochlorides
BF3K
NHNH2 HCl
BF3K
NHNH2 HCl
R
R
Pd(NH3)2Cl2 K2CO3
Pd(NH3)2Cl2 K2CO3
R
R
CuCl2.2H2O H2O, RT
CuCl2.2H2O H2O, RT
b
b
Entry
Yield (%)
Entry
Yield (%)
1
91
24
25
26
27
28
29
88
95
89
83
91
87
2
3
4
5
6
89
84
86
81
92
7
8
87
85
30
31
81
76
9
80
32
82
1
1
0
1
90
94
33
34
79
82
1
1
1
2
3
4
88
81
84
35
36
37
73
85
77
(Continues)

6
of 9
WANG ET AL.
TABLE 3 (Continued)
BF3K
NHNH2 HCl
BF3K
NHNH2 HCl
R
R
Pd(NH3)2Cl2 K2CO3
Pd(NH3)2Cl2 K2CO3
R
R
CuCl2.2H2O H2O, RT
CuCl2.2H2O H2O, RT
b
b
Entry
Yield (%)
Entry
Yield (%)
15
16
17
18
62
38
39
40
41
76
71
87
61
82
72
86
1
2
9
0
83
75
42
43
87
80
2
1
78
44
74
2
2
2
3
66
80
45
46
78
66
a
.
Reaction conditions: potassium aryltrifluoroborates (0.6 mmol), arylhydrazine hydrochlorides (0.5 mmol), Pd(NH
1 mmol), H O (1.0 ml) under 25 °C for 12 hours under air unless otherwise indicated. Isolated coupling yield.
)
3 2
Cl
2
(1 mol%), CuCl
2
2H
2
2 3
O (2 mol%), K CO
(
2
yields (Table 3, entries 42‐43). It is worth noting that this
protocol is also applicable to heterocyclic aromatics such
as pyridine and thiazole (Table 3, entries 44‐46).
We suspected that the atmospheric oxygen might be
involved in the denitrogenative Suzuki‐type coupling reac-
tions because the cross‐coupling yields were much higher
reaction conditions. No cross‐coupling product was
detected in the absence of the copper co‐catalyst, neither
under nitrogen atmosphere nor under pure oxygen atmo-
sphere. The cross‐coupling product yield was found to be
.
only about 18% in the presence of 2 mol% CuCl 2H O
2
2
under nitrogen gas protection. However, the cross‐cou-
pling product was isolated with a decent yield of 80% when
the reaction was performed under pure oxygen atmo-
sphere in the presence of the copper co‐catalyst, indicating
than the CuCl amount. In order to test this hypothesis,
2
we examined the Pd(NH ) Cl ‐catalyzed denitrogenative
3
2
2
cross‐coupling reaction of p‐tolylhydrazine hydrochloride
and potassium phenyltrifluoroborate under different
.
that the atmospheric oxygen and CuCl 2H O were both
2
2

WANG ET AL.
7 of 9
SCHEME 2 Control experiments
3
| CONCLUSION
In summary, we report the Pd‐catalyzed oxidative
denitrogenative Suzuki‐type cross‐coupling reaction
of arylhydrazine hydrochlorides with potassium
aryltrifluoroborates which offers environmentally friendly
access to biaryls in water with N as the by‐products. The
2
reaction was performed at atmosphere in the presence of
.
catalytic CuCl 2H O, which act as the terminal oxidant.
2
2
The substrate scope was found to be very general for the
cross‐coupling reaction under the optimized reaction
conditions, and a range of biaryls were prepared in
moderate to good yields. It is foreseeable that this aqueous
environmentally friendly protocol will be an attractive
strategy for the synthesis of biaryls in future.
ACKNOWLEDGEMENTS
SCHEME 3 Proposed mechanism
This work was Supported by the National Natural
Science Foundation of China (No. 21402123 and
No. 21172149), the Science Technology Project of
Shaoxing City (No. 2017B70053) and the Zhejiang
Provincial Natural Science Foundation of China (No.
LY18B020006 and No. LQ14B020001).
essential for the Pd‐catalyzed denitrogenative cross‐cou-
pling (Scheme 2).
A possible mechanism for our denitrogenative Suzuki‐
type cross‐coupling reaction of arylhydrazine hydrochlo-
rides with potassium aryltrifluoroborates is shown in
Scheme 3. The arylhydrazines can be oxidized by CuCl2
to form aryldiazenes, and Cu(II) could be regenerated by
oxidation of Cu(II) with molecular oxygen. Subsequently
aryldiazenes undergoes Pd(II)‐catalyst (A) followed
ORCID
Kai Cheng http://orcid.org/0000-0002-7080-8270
by the formation of ArPdL Cl intermediate (B) via
2
transmetalation with concomitant loss of a neutral N2
molecule. The function of nitrogen‐containing ligand in
the catalytic cycle might be facilitate the process of
transmetalation with aryldiazenes. The transmetallation
with Ar’BF K generated intermediate Ar‐Pd(II)L ‐Ar’ (C)
REFERENCES
[
[
1] R. Jana, T. P. Pathak, M. S. Sigman, Chem. Rev. 2011, 111, 1417.
2] A. de Meijere, F. Diederich (Eds), Metal‐Catalyzed
Cross‐Coupling Reactions, 2nd ed., Wiley‐VCH, Weinheim,
Germany 2004.
3
2
with the assistance of base along with BF3 as the
by‐products. Afterward, reductive elimination of the
denitrogenative coupling product leads to formation of
the reductive Pd(0)L2 species, which will be oxidized
[
[
[
[
3] M.‐O. Simon, C.‐J. Li, Chem. Soc. Rev. 2012, 41, 1415.
4] C.‐J. Li, Acc. Chem. Res. 2010, 43, 581.
5] R. N. Butler, A. G. Coyne, Chem. Rev. 2010, 110, 6302.
6] C. I. Herrerías, X. Yao, Z. Li, C.‐J. Li, Chem. Rev. 2007,
into the oxidative Pd(II)L species by Cu(II) to complete
2
107, 2546.
the catalytic cycle. Cu(I) is then oxidized by oxygen
to regenerate Cu(II) which makes the usage of copper to
catalytic cycle.
[7] A. Chanda, V. V. Fokin, Chem. Rev. 2009, 109, 725.
[8] N. Miyaura, A. Suzuki, Chem. Rev. 1995, 95, 2457.

8
of 9
WANG ET AL.
[
9] S. R. Chemler, D. Trauner, S. J. Danishefsky, Angew. Chem. Int.
Ed. 2001, 40, 4544.
[40] G. C. Senadi, W. P. Hu, T. Y. Lu, A. M. Garkhedkar, J. K.
Vandavasi, J. J. Wang, Org. Lett. 2015, 17, 1521.
[
10] G. C. Fu, A. F. Littke, Angew. Chem., Int. Ed. 2002, 41, 4176.
11] G. A. Molander, B. Canturk, Angew. Chem. Int. Ed. 2009,
[41] Q. Wu, P. Liu, Y.‐M. Pan, X.‐L. Xu, H.‐S. Wang, RSC Adv. 2012,
2
, 10167.
[
4
8, 9240.
[42] X. Wang, Y.‐M. Pan, X.‐C. Huang, Z.‐Y. Mao, H.‐S. Wang, Org.
Biomol. Chem. 2014, 12, 2028.
[
[
12] A. Suzuki, Angew. Chem. Int. Ed. 2011, 50, 672.
[
43] T. Taniguchi, H. Zaimoku, H. Ishibashi, Chem. – Eur. J. 2011,
7, 4307.
[44] H. Jasch, J. Scheumann, M. R. Heinrich, J. Org. Chem. 2012,
7, 10699.
13] D. G. Hall (Ed), Boronic acids: preparation and application in
organic synthesis, medicine and materials, 2nd ed., Wiley‐
VCH., Weinheim 2011 171.
1
7
[
14] H. Bonin, E. Fouquet, F.‐X. Felpin, Adv. Synth. Catal. 2011,
3
53, 3063.
[45] T. Jiang, S.‐Y. Chen, H. Zhuang, R.‐S. Zeng, J.‐P. Zou, Org.
[
[
15] G. A. Molander, L. N. Cavalcanti, J. Org. Chem. 2012, 77, 4402.
Biomol. Chem. 2014, 12, 6922.
16] G. A. Molander, L. N. Cavalcanti, C. García‐García, J. Org.
Chem. 2013, 78, 6427.
[46] Y. Li, W. Liu, C. Kuang, Tetrahedron Lett. 2014, 55, 4549.
[
47] J. Hofmann, H. Jasch, M. R. Heinrich, J. Org. Chem. 2014,
[
[
[
17] S. Darses, J.‐P. Genet, Chem. Rev. 2008, 108, 288.
79, 2314.
18] G. A. Molander, N. Ellis, Acc. Chem. Res. 2007, 40, 275.
[48] P. Patil, A. Nimonkar, K. G. Akamanchi, J. Org. Chem. 2014,
9, 2331.
7
19] A. Molnar (Ed), Palladium‐Catalyzed Coupling Reaction, Wiley‐
VCH, Weinheim 2013.
[49] T. Taniguchi, M. Imoto, M. Takeda, T. Nakai, M. Mihara, T.
Mizuno, A. Nomoto, A. Ogawa, Synthesis 2017, 49, 1623.
[
[
[
[
[
[
20] T. E. Barder, S. L. Buchwald, Org. Lett. 2004, 6, 2649.
21] G. A. Molander, S. R. Wisniewski, J. Org. Chem. 2014, 79, 6663.
22] A. Joliton, E. M. Carreira, Org. Lett. 2013, 15, 5147.
23] G. A. Molander, B. Biolatto, Org. Lett. 2002, 4, 1867.
24] L. Zhang, T. Meng, J. Wu, J. Org. Chem. 2007, 72, 9346.
25] C. M. So, C. P. Lau, A. S. C. Chan, F. Y. Kwong, J. Org. Chem.
[
50] J. Hofmann, T. Clark, M. R. Heinrich, J. Org. Chem. 2016,
81, 9785.
[
51] M.‐K. Zhu, J.‐F. Zhao, T.‐P. Loh, Org. Lett. 2011, 13, 6308.
52] Y. Bai, L. Mai, H. Kim, H. Liao, X.‐W. Liu, J. Org. Chem. 2013,
[
7
8, 8821.
53] Y. Su, X. Sun, G. Wu, N. Jiao, Angew. Chem. Int. Ed. 2013,
2, 9808.
[
2
008, 73, 7731.
26] G. W. Kabalka, L.‐L. Zhou, A. Naravane, Tetrahedron Lett.
006, 47, 6887.
27] Z.‐Y. Wang, Q.‐N. Ma, R.‐H. Lia, L.‐X. Shao, Org. Biomol. Chem.
013, 11, 7899.
28] W. K. Chow, C. M. So, C. P. Lau, F. Y. Kwong, J. Org. Chem.
010, 75, 5109.
29] C. M. So, C. P. Lau, F. Y. Kwong, Angew. Chem. Int. Ed. 2008,
7, 805.
30] J.‐J. Dai, J.‐H. Liu, D.‐F. Luo, L. Liu, Chem. Commun. 2011,
7, 677.
5
[
[
[
[
[
[
54] J.‐B. Liu, F. J. Chen, N. Liu, J. Hu, RSC Adv. 2015, 5, 45843.
55] J. ‐B. Liu, H. ‐P. Zhou, Y. ‐Y. Peng, Tetrahedron Lett. 2014,
2
[
5
5, 2872.
56] H.‐P. Zhou, J.‐B. Liu, J.‐J. Yuan, Y.‐Y. Peng, RSC Adv. 2014,
, 25576.
57] Z. Peng, G. Hu, H. Qiao, P. Xu, Y. Gao, Y. Zhao, J. Org. Chem.
014, 79, 2733.
2
[
[
[
[
[
[
4
2
2
4
58] J.‐B. Liu, H. Yan, H.‐X. Chen, Y. Luo, J. Weng, G. Lu, Chem.
Commun. 2013, 49, 5268.
4
59] K. Cheng, G. Wang, M. Meng, C. Qi, Org. Chem. Front. 2017,
[
31] Q. Wang, Y. Su, L. Li, H. Huang, Chem. Soc. Rev. 2016, 45, 1257.
32] K. Ouyang, W. Hao, W.‐X. Zhang, Z. Xi, Chem. Rev. 2015,
4
, 398.
[
60] X. Wang, Y. Huang, Y. Xu, X. Tang, W. Wu, H. Jiang, J. Org.
Chem. 2017, 82, 2211.
1
15, 12045.
[
[
33] S. Cacchi, E. Caponetti, M. A. Casadei, A. Di Giulio, G. Fabrizi,
G. Forte, A. Goggiamani, S. Moreno, P. Paolicelli, F. Petrucci,
Green Chem. 2012, 14, 317.
61] P. Yao, Appl. Organometal. Chem. 2014, 28, 194.
[62] J.‐B. Liu, L. Nie, H. Yan, L.‐H. Jiang, J. Weng, G. Lu, Org.
Biomol. Chem. 2013, 11, 8014.
34] K. Cheng, C. Wang, Y. Ding, Q. Song, C. Qi, X.‐M. Zhang,
J. Org. Chem. 2011, 76, 9261.
[
63] P. Chauhan, M. Ravi, S. Singh, K. S. Raju, V. Bajpai, B. Kumar,
[
35] B. Schmidt, F. Hoelter, Org. Biomol. Chem. 2011, 9, 4914.
36] K. Cheng, B. Zhao, S. Hu, X.‐M. Zhang, C. Qi, Tetrahedron Lett.
P. P. Yadav, RSC Adv. 2014, 4, 43336.
[
[64] Y. Chen, S. Guo, K. Li, J. Qu, H. Yuan, Q. Hua, B. Chen, Adv.
Synth. Catal. 2013, 355, 711.
2
013, 54, 6211.
[
37] B. Schmidt, R. Berger, Adv. Synth. Catal. 2013, 355, 463.
[65] W. Xu, G. Hu, P. Xu, Y. Gao, Y. Yin, Y. Zhao, Adv. Synth. Catal.
2
014, 356, 2948.
[
38] T. Tomakinian, R. Guillot, C. Kouklovsky, G. Vincent, Chem.
Commun. 2016, 52, 5443.
[66] Y. Zhao, Q. Song, Chem. Commun. 2015, 51, 13272.
[
39] W. Wei, J. Wen, D. Yang, M. Guo, Y. Wang, J. You, H. Wang,
[67] H. Zhang, C. Wang, Z. Li, Z. Wang, Tetrahedron Lett. 2015,
56, 5371.
Chem. Commun. 2015, 51, 768.

WANG ET AL.
9 of 9
[
68] J. B. Bharate, S. Abbat, R. Sharma, P. V. Bharatam, R. A.
SUPPORTING INFORMATION
Vishwakarma, S. B. Bharate, Org. Biomol. Chem. 2015, 13, 5235.
Additional Supporting Information may be found online
in the supporting information tab for this article.
[
69] M. Li, Y. Ye, Chem. Cat. Chem. 2015, 7, 4137.
[
70] S.‐Y. Chen, R.‐S. Zeng, J.‐P. Zou, O. T. Asekun, J. Org. Chem.
2
014, 79, 1449.
How to cite this article: Wang G, Meng M, Deng
L, Cheng K, Qi C. Denitrogenative Pd/Cu‐catalyzed
Suzuki‐type Cross‐coupling of Aryltrifluoroborates
with Arylhydrazine Hydrochlorides in Water under
Room Temperature. Appl Organometal Chem. 2017;
e4203. https://doi.org/10.1002/aoc.4203
[
71] M. Ravi, P. Chauhan, R. Kant, S. K. Shukla, P. P. Yadav, J. Org.
Chem. 2015, 80, 5369.
[
[
72] J.‐B. Liu, H. Yan, G. Lu, Tetrahedron Lett. 2013, 54, 891.
73] J. Liu, S. Yuan, X. Song, G. Qiu, Chin. J. Org. Chem. 2016,
3
6, 1790.