Base-promoted silver-catalyzed protodeboronation of arylboronic acids and esters

Article abstract of DOI:10.1039/c4ra16323k

The silver-catalyzed protodeboronation of arylboronic acids and esters in the presence of a base was developed. This method was highly efficient for the protodeboronation of various arylboronic acids and was applied to an efficient deprotection of bifunctional amine under mild conditions. A base-promoted mechanism was proposed. This journal is

Full text of DOI:10.1039/c4ra16323k

RSC Advances
View Article Online
View Journal | View Issue
COMMUNICATION
Base-promoted silver-catalyzed
protodeboronation of arylboronic acids and esters†
Cite this: RSC Adv., 2015, 5, 15354
Chun Liu,* Xinmin Li and Yonghua Wu
Received 13th December 2014
Accepted 26th January 2015
DOI: 10.1039/c4ra16323k
www.rsc.org/advances
The silver-catalyzed protodeboronation of arylboronic acids and Although lots of efforts have been devoted to improve the
esters in the presence of a base was developed. This method was efficiency of the protodeboronation, the reported protocols still
highly efficient for the protodeboronation of various arylboronic suffer from a limited substrate scope. In a previous report, we
acids and was applied to an efficient deprotection of bifunctional have developed a copper-catalyzed protodeboronation of aryl-
9
amine under mild conditions. A base-promoted mechanism was boronic acids under aqueous and aerobic conditons. Herein,
proposed.
we report a general and efficient approach for the silver-
catalyzed protodeboronation of a broad range of aryl boronic
acids and esters in the presence of a base in aqueous media.
Both electron-rich and electron-poor arylboronic acids could
afford the products in excellent yields under the optimized
conditions.
Initially, we investigated the inuences of different reaction
parameters on the protodeboronation reaction. The proto-
deboronation of 4-(diphenylamino)phenylboronic acid was
chosen as a model reaction to screen the reaction conditions. In
Organoboronic acids and their derivatives have been exten-
sively used in organic synthesis, in particular, in the transition-
metal-catalyzed Suzuki–Miyaura cross-coupling reaction, due
to their unique reactivity, ready availability, and low toxicity.
The protodeboronation is a common, sometimes even domi-
1
nant side reaction in the Suzuki–Miyaura cross-coupling reac-
2
tion. Over the past decades, the protodeboronation was
considered to be useless in organic syntheses, thus, only a few
studies were reported in the literature. Until recent years, the
2 3 4 2
the presence of Ag O (6 mol%) and K PO $3H O (0.2 mmol),
3
protodeboronation has attracted increasing attention, and
remarkable progress in the application of protodeboronation
4
to organic syntheses has been achieved by several groups. For
Table 1 Effect of solvent on protodeboronation of 4-(diphenylamino)
5
a
example, Aggarwal's group reported a series of investigations phenylboronic acid
on highly enantioselective syntheses of natural and non-
natural products using the protodeboronation of allylic and/
or alkyl boronic esters, which greatly promoted the applica-
tion of protodeboronation. However, the protodeboronation of
arylboronic acids and esters has received little attention as a
b
Entry
Solvent
Yield (%)
viable synthetic method from the synthetic community. In
6
1
2
3
4
5
6
7
8
9
EtOH/H O
DMF/H O
2
98
92
90
91
22
35
70
45
38
2013, Cheon's group reported metal-free thermal proto-
2
deboronation of ortho- and para-phenol boronic acids in wet
2
i-PrOH/H O
7
DMSO. Very recently, the same group has successfully
EtOH
DMF
Toluene
Ethylene glycol
PEG-400
extended the metal-free thermal protodeboronation to variable
8
electron-rich arylboronic acids. In 2014, Perrin's group devel-
oped an efficient protocol for the protodeboronation of
electron-decient 2,6-disubstituted arylboronic acids at pH 12.
2
H O
a
Reaction conditions: 4-(diphenylamino)phenylboronic acid (0.2 mmol),
State Key Laboratory of Fine Chemicals, Dalian University of Technology, Linggong
Road 2, 116024, Dalian, China. E-mail: cliu@dlut.edu.cn; Tel: +86 411 84986182
ꢀ
Ag
3
2
O (6 mol%), K
3
PO
4
$3H
2
O (0.2 mmol), solvent (0.5 mL/0.5 mL), 80 C,
b
0 min under air. The reaction was monitored by TLC. Isolated yields.
†
Electronic supplementary information (ESI) available: Experimental detail and
characterization of protodeboronation products. See DOI: 10.1039/c4ra16323k
15354 | RSC Adv., 2015, 5, 15354–15358
This journal is © The Royal Society of Chemistry 2015

View Article Online
Communication
RSC Advances
ꢀ
various solvents were tested at 80 C. As shown in Table 1, the absence of a silver catalyst (Table 2, entry 16). The pro-
excellent yields could be obtained in EtOH/H O, DMF/H O, todeboronation using 0.1 equiv. K PO $3H O or K PO $7H O
2
2
3
4
2
3
4
2
i-PrOH/H O and EtOH (Table 1, entries 1–4), and 50% aqueous as base was also carried out, providing 91% and 80% yields
2
ethanol was the best choice.
Next, we explored the effects of metal-catalysts on the no products were observed in the absence of a base (Table 2,
same model reaction. All of the tested silver catalysts gave entry 19) or in the presence of CH COOH (Table 2, entry 20).
satisfactory results (Table 2, entries 1–5), and a 97% yield was The results show that the combination of a silver catalyst and
obtained within shorter reaction time using AgNO as catalyst a base plays a crucial role in the high efficiency on this
Table 2, entry 2). Subsequently, the effects of bases were reaction.
investigated. As for the inorganic bases, K PO $3H O gave a Based on the above results, a possible mechanism for the
in 150 min, respectively (Table 2, entries 17 and 18). However,
3
3
(
3
4
2
satisfactory yield (97%), however, others including NaOH, silver-catalyzed protodeboronation is depicted. As shown in
CH ONa and K CO were less effective than K PO $3H O Scheme 1, initially, arylboronic acid as a mild organic Lewis
3
2
3
3
4
2
(
Table 2, entries 6–8). Compared to the inorganic bases, the acid quickly transforms to a tetrahedral adduct arylboronate
organic bases demonstrated higher efficiency (Table 2, entries anion under alkaline conditions. Then, the silver ion attacks
–12). The best base for this transformation is Et N, which this tetrahedral adduct to provide an arylsilver intermediate
provided a 96% yield in 10 min (Table 2, entry 12). In order (a). Subsequently, the arylsilver undertakes the protolysis with
9
3
+
to understand the function of the base in the present Et
3
N H to deliver the arenes. The catalytic cycle is completed
protocol, we investigated the effects of the loading of Et N in by generating the silver ion, which is accordance with the
3
10
the same protodeboronation (Table 2, entries 12–15). Inter- literature reports. In this process, the base performs as a
estingly, the reaction still afforded the product in a high yield promoter to accelerate the formation of arylboronate anion,
of 97% in 60 min by using 0.06 equiv. Et
equal amount of silver catalyst (Table 2, entry 14). While arylboronic acids.
further decreasing the amount of Et N to 0.03 equiv., the With the optimized conditions at hand, we further
3
N which was the which leads to a fast silver-catalyzed protodeboronation of
3
yield was decreased to 67% (Table 2, entry 15). It is worth explored the scope and limitations of substrates for this
noting that only a 16% yield of the product was obtained in protocol. As shown in Table 3, the electronic effects of the
substituents on the arylboronic acids had little inuence
(Table 3, entries 1–10). Phenylboronic acid performed the
protodeboronation smoothly and afforded a 95% yield of
product (Table 3, entry 1). Both electron-poor (Table 3, entries
Table 2 Screening of optimum conditions for the protodeboronation
of 4-(diphenylamino)phenylboronic acid
2
–8) and electron-rich (Table 3, entries 9 and 10) arylboronic
a
acids underwent the protodeboronation quickly and provided
the products in excellent yields. For example, p-tolylboronic
acid, which was ineffective in the metal-free thermal proto-
7
deboronation, could afford the product in 92% yield in 10
min (Table 3, entry 10), and 4-(triuoromethyl)phenylboronic
b
Entry Catalyst Base
Time (min) Yield (%) acid was also very effective in this system compared to a
8
previous method (Table 3, entry 6). A large array of func-
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
Ag
AgNO
Ag
AgBF
AgOAc
2
CO
3
K
K
K
K
K
3
3
3
3
3
PO
PO
PO
PO
PO
4
4
4
4
4
$3H
$3H
$3H
$3H
$3H
2
2
2
2
2
O
O
O
O
O
25
25
30
30
30
30
30
30
30
13
12
10
55
60
420
60
96
97
97
88
94
59
66
57
95
97
97
96
97
97
67
16
91
80
0
tional groups was tolerated in this system. The arylboronic
acids with a –CH or –NO group at the meta-position also
gave excellent yields in 20 min (Table 3, entries 11 and 12).
3
O
3
2
2
4
The effects of steric hindrance were tested. The standard
AgNO
AgNO
AgNO
AgNO
AgNO
AgNO
AgNO
AgNO
AgNO
AgNO
—
3
3
3
3
3
3
3
3
3
3
NaOH
CH ONa
CO
i-PrNH
conditions
were
proved
to
be
efficient
to
2-
3
K
2
3
2
0
1
2
3
4
5
6
7
8
9
0
3
(n-Pr) N
DBU
Et
Et
Et
Et
Et
3
3
3
3
3
N
N (0.10 equiv.)
N (0.06 equiv.)
N (0.03 equiv.)
N (0.06 equiv.)
AgNO
AgNO
AgNO
AgNO
3
3
3
3
K
K
3
PO
PO
4
$3H
$7H
2
O (0.10 equiv.) 150
O (0.10 equiv.) 150
3
4
2
—
CH
60
60
3
COOH
0
a
Reaction conditions: 4-(diphenylamino)phenylboronic acid (0.2 mmol),
ꢀ
catalyst (6 mol%), base (0.2 mmol), EtOH/H
under air. The reaction was monitored by TLC. Isolated yields.
2
O (0.5 mL/0.5 mL), 80 C,
b
Scheme 1 A plausible mechanism of protodeboronation.
This journal is © The Royal Society of Chemistry 2015
RSC Adv., 2015, 5, 15354–15358 | 15355

View Article Online
RSC Advances
Communication
a
Table 3 Protodeboronation reaction of arylboronic acids and esters
Table 3 (Contd.)
AgNO ;Et3N
3
AgNO ;Et3N
Ar-BR ƒƒƒƒƒƒ ƒƒ !Ar-H
3
EtOH=H O
Ar-BR ƒƒƒƒƒƒ ƒƒ !Ar-H
2
EtOH=H O
2
b
b
Entry Ar-BR
Product
Time (min) Yield (%)
Entry Ar-BR
Product
Time (min) Yield (%)
1
2
1
2
15
95
97
2
2
2
4
5
6
1
50
96
96
92
23
15
15
15
18
17
c
c
14 40
14 55
3
4
5
6
7
3
4
5
6
7
96
98
95
98
98
e
2
7
14 180
0
a
Reaction conditions: arylboronic acid and esters (0.2 mmol), AgNO
3
ꢀ
(6.0 mol%), Et
3
N (0.2 mmol), EtOH/H
2
O (0.5 mL/0.5 mL), 80 C,
b
c
under air. The reaction was monitored by TLC. GC yields. Isolated
yields. Phenylboronic acid (2 mmol). Anhydrous toluene as solvent,
d
e
2
under N .
8
9
8
9
10
10
97
98
92
1
1
0
1
10 10
10 14
94
96
96
1
1
2
3
11 20
Scheme
2 Silver-catalyzed protodeboronation of a heterocyclic
adduct.
9
15
1
4
10 13
92
methoxyphenylboronic acid and o-tolylboronic acid (Table 3,
entries 13 and 14). It's worth noting that heterocyclic boronic
acids exhibited high reactivity in this protocol (Table 3,
entries 15–18). Various polycyclic aromatic boronic acids,
which were rarely tested in literature, were highly effective in
this system (Table 3, entries 19–21). For example, 4-(9H-
carbozol-9-yl)phenylboronic acid afforded the product in 98%
yield within 15 min (Table 3, entry 20). In addition, the pro-
todeboronation could be scaled up to 2 mmol, and a 95%
yield was readily achieved in the case of phenylboronic acid
1
1
1
1
1
5
6
7
8
9
12 15
12 15
13 25
13 270
14 10
98
97
95
98
97
(Table 3, entry 22). To further explore the scope, the proto-
c
deboronation of organoboronic esters were tested. As expec-
ted, the cyclic esters of arylboronic acids gave satisfactory
results (Table 3, entries 23–26). However, 4-(diphenylamino)
phenylboronic acid pinacol ester did not undergo proto-
deboronation when anhydrous toluene was used as solvent
c
2
2
0
1
15 15
15 15
98
97
c
2
under N (Table 3, entry 27). This result could prove that the
proton is transferred from the protic solvent, which is
6
consistent with Cheon's report.
d
2
2
2
3
1
1
15
35
95
There are only a few reports on the application of proto-
6,11
deboronation of arylboronic acids.
For example, phenyl-
96
boronic acid reacts with o-phenylendiamine to give a stable
heterocyclic adduct (Scheme 2, compound 16) for the
protection of free amino groups. However, the hydrolysis of
15356 | RSC Adv., 2015, 5, 15354–15358
This journal is © The Royal Society of Chemistry 2015

View Article Online
Communication
RSC Advances
11
adduct 16 required a relatively long period of eight hours.
The procedure for protodeboronation of 2-phenyl-2,3-dihydro-
Thus, we further studied the deprotection of the adduct 16 in 1H-1,3,2-benzodiazaborole (16)
the present silver-catalyzed protodeboronation system. As
A mixture of 2-phenyl-2,3-dihydro-1H-1,3,2-benzodiazaborole
shown in Scheme 2, the protodeboronation performed effec-
tively and a 93% yield of o-phenylendiamine 17 was obtained
in 30 min.
(16) (0.2 mmol, 38.81 mg), AgNO
3
(6 mol%, 2.04 mg), Et
3
N
(
0.2 mmol, 20.24 mg) and EtOH/H
2
O (0.5 mL/0.5 mL) was
ꢀ
heated at 80 C in Schlenk ask for 30 min. The mixture was
added to brine (10 mL) and extracted three times with ethyl
acetate (10 mL). The solvent was concentrated under vacuum,
and the product was isolated by short-column chromatography
using petroleum ether/ethyl acetate (1 : 1) and white solid was
obtained (20.2 mg, 93% yield).
Conclusions
In conclusion, we have developed a general, simple and highly
efficient method for the silver-catalyzed protodeboronation of
arylboronic acids and esters in aqueous media. The reactions
3
proceeded smoothly in the presence of Et N under aerobic
Acknowledgements
conditions. This method could be applied to a facile and
efficient deprotection of bifunctional amines under mild
conditions. The synthetic application of this approach is
currently under investigation in our laboratory.
The authors thank the nancial support from the National
Natural Science Foundation of China (21276043).
References
Experimental
Materials and methods
1
(a) N. Miyaura, in Cross-coupling reactions, Springer, 2002,
pp. 11–59; (b) D. G. Hall, Boronic Acids: Preparation and
Applications in Organic Synthesis, Medicine and Materials,
John Wiley & Sons, 2012; (c) C. Liu, Q. Ni, P. Hu and
J. Qiu, Org. Biomol. Chem., 2011, 9, 1054–1106; (d) C. Liu,
Q. Ni, F. Bao and J. Qiu, Green Chem., 2011, 13, 1260–
All arylboronic acids and esters, metal catalysts were used as
received. Other reagents and solvents were obtained from
commercial suppliers and used without further purication. All
reagents were weighed and handled in air at room temperature.
1
H NMR spectra were recorded on a 400 MHz spectrometer
1
2
266; (e) C. Liu, Y. Zhang, N. Liu and J. Qiu, Green Chem.,
012, 14, 2999–3003; (f) N. Liu, C. Liu and Z. Jin, Green
using TMS as internal standard. The yields of liquid products
were determined by GC using biphenyl as an internal standard,
and the solid products were isolated by short chromatography
Chem., 2012, 14, 592–597; (g) C. Liu, X. Rao, Y. Zhang,
X. Li, J. Qiu and Z. Jin, Eur. J. Org. Chem., 2013, 4345–
on a silica gel (200–300 mesh) column using petroleum ether
4350; (h) C. Liu, X. Rao, X. Song, J. Qiu and Z. Jin, RSC
ꢀ
(
60–90 C), unless otherwise noted. Compounds described in
Adv., 2013, 3, 526–531.
(a) A. J. Lennox and G. C. Lloyd-Jones, Angew. Chem., Int. Ed.,
1
the literature were characterized by H NMR spectra compared
to reported data.
2
3
2
013, 52, 7362–7370; (b) N. Miyaura and A. Suzuki, Chem.
Rev., 1995, 95, 2457–2483; (c) D. V. Partyka, Chem. Rev.,
011, 111, 1529–1595.
(a) A. D. Ainley and F. Challenger, J. Chem. Soc., 1930, 2171–
2
Typical procedure for protodeboronation of arylboronic acids
and esters
2
1
180; (b) H. G. Kuivila and K. Nahabedian, J. Am. Chem. Soc.,
961, 83, 2159–2163; (c) H. G. Kuivila, J. F. Reuwer Jr and
A mixture of arylboronic acid or ester (0.2 mmol), AgNO
6 mol%), Et N (0.2 mmol) and EtOH/H O (0.5 mL/0.5 mL) was
3
(
3
ꢀ
2
J. A. Mangravite, Can. J. Chem., 1963, 41, 3081–3090; (d)
H. G. Kuivila, J. F. Reuwer and J. A. Mangravite, J. Am.
Chem. Soc., 1964, 86, 2666–2670.
stirred at 80 C in air for the indicated time. The mixture was
added to brine (2 mL) and extracted three times with ethyl
acetate (2 mL). The combined organic layers were dried over
sodium sulfate and was analysed by gas chromatography using
biphenyl as internal standard.
4
5
(a) R. Y. Lai, C. L. Chen and S. T. Liu, J. Chin. Chem. Soc.,
2006, 53, 979–985; (b) L. M. Klingensmith, M. M. Bio and
G. A. Moniz, Tetrahedron Lett., 2007, 48, 8242–8245; (c)
M. Veguillas, M. Ribagorda and M. C. Carreno, Org. Lett.,
2011, 13, 656–659.
Typical procedure for protodeboronation of polycyclic
aromatic boronic acids and esters
(a) S. Nave, R. P. Sonawane, T. G. Elford and V. K. Aggarwal, J.
Am. Chem. Soc., 2010, 132, 17096–17098; (b) T. G. Elford,
S. Nave, R. P. Sonawane and V. K. Aggarwal, J. Am. Chem.
Soc., 2011, 133, 16798–16801; (c) S. Roesner,
J. M. Casatejada, T. G. Elford, R. P. Sonawane and
V. K. Aggarwal, Org. Lett., 2011, 13, 5740–5743; (d)
M. J. Hesse, C. P. Butts, C. L. Willis and V. K. Aggarwal,
Angew. Chem., Int. Ed., 2012, 124, 12612–12616; (e)
C. G. Watson and V. K. Aggarwal, Org. Lett., 2013, 15, 1346–
A mixture of arylboronic acid or esters (0.2 mmol), AgNO
6 mol%), Et N (0.2 mmol) and EtOH/H O (0.5 mL/0.5 mL) was
3
(
3
ꢀ
2
stirred at 80 C in air for the indicated time. The mixture was
added to brine (10 mL) and extracted three times with
ethyl acetate (10 mL). The solvent was concentrated under
vacuum, and the product was isolated by short-column
chromatography.
This journal is © The Royal Society of Chemistry 2015
RSC Adv., 2015, 5, 15354–15358 | 15357

View Article Online
RSC Advances
Communication
1
8
349; (f) R. Rasappan and V. K. Aggarwal, Nat. Chem., 2014, 6,
10–814.
9 C. Liu, X. Li, Y. Wu and J. Qiu, RSC Adv., 2014, 4, 54307–
54311.
6
7
8
C.-Y. Lee, S.-J. Ahn and C.-H. Cheon, J. Org. Chem., 2013, 78, 10 (a) T. Furuya, A. E. Strom and T. Ritter, J. Am. Chem. Soc.,
1
2154–12160.
S.-J. Ahn, C.-Y. Lee, N.-K. Kim and C.-H. Cheon, J. Org. Chem.,
014, 79, 7277–7285.
J. Lozada, Z. Liu and D. M. Perrin, J. Org. Chem., 2014, 79,
365–5368.
2009, 131, 1662–1663; (b) W. T. Miller Jr and K. K. Sun, J.
Am. Chem. Soc., 1970, 92, 6985–6987.
2
11 (a) G. Kaupp, M. R. Naimi-Jamal and V. Stepanenko, Chem.–
Eur. J., 2003, 9, 4156–4161; (b) T. Okuyama, K. Takimoto and
T. Fueno, J. Org. Chem., 1977, 42, 3545–3549.
5
15358 | RSC Adv., 2015, 5, 15354–15358
This journal is © The Royal Society of Chemistry 2015