Practical Transition-Metal-Free Protodeboronation of Arylboronic Acids in Aqueous Sodium Hypochlorite

Article abstract of DOI:10.1055/s-0040-1706298

A concise and practical method was developed for the protodeboronation of arylboronic acids under mild conditions in aqueous NaClO at 100 °C. The strategy is low-cost, transition-metal-free, and base-free.

Full text of DOI:10.1055/s-0040-1706298

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Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart
2020, 31, A–D
letter
A
en
M. Li et al.
Letter
Synlett
Practical Transition-Metal-Free Protodeboronation of Arylboronic
Acids in Aqueous Sodium Hypochlorite
Minxin Li◊
R
R
20 mol% TBAB
Yanling Tang◊
Jinchun Gao
Gaoxiong Rao
Zewei Mao*
H
B(OH)2
NaClO (aq), 100 °C
17 examples
72–91% yields
low-cost
base-free
transition-metal-free
College of Pharmaceutical Science, Yunnan University of Chinese Medicine,
Kunming 650500, P. R. of China
maozw@ynutcm.edu.cn
ydmason@163.com
◊These authors contributed equally
Corresponding Author
Received: 03.08.2020
Accepted after revision: 26.08.2020
Published online: 07.10.2020
in concentrated acid.7 S.-T. Liu and co-workers reported that
palladium nanoparticles efficiently catalyzed the deborona-
tion of arylboronic acids in an alcoholic medium under ba-
sic conditions.8 C. Liu et al. developed an efficient protocol
for the copper- and silver-catalyzed protodeboronation of
arylboronic acids in ethanolic media.9,10 Although many re-
ported methods are available for the protodeboronation of
arylboronic acids through transition metal-catalyzed or
other means, most require harsh conditions, such as the use
of metallic salts as catalytic systems, bases, concentrated
acids, and high temperatures, or use environmentally dam-
aging solvents.6–11 There is therefore still a need to develop
efficient and green conditions for protodeboronation of ar-
ylboronic acids.
In previous work, when we performed Pd-catalyzed oxi-
dative homocouplings of arylboronic acids in aqueous NaClO,
we found that a few protodeboronated byproducts were
formed under these conditions.12 This indicated that aryl-
boronic acids can undergo protodeboronation in aqueous
NaClO, and that a metal catalytic system might be dispens-
able in this reaction. To the best of our knowledge, few re-
ports have appeared on transition-metal-free conditions for
this reaction.13 We therefore explored and developed an ef-
ficient, transition-metal-free and base-free method for the
protodeboronation of arylboronic acids in aqueous NaClO
under mild conditions (Scheme 1).
DOI: 10.1055/s-0040-1706298; Art ID: st-2020-v0425-l
Abstract A concise and practical method was developed for the pro-
todeboronation of arylboronic acids under mild conditions in aqueous
NaClO at 100 °C. The strategy is low-cost, transition-metal-free, and
base-free.
Key words protodeboronation, arylboronic acids, sodium hypochlo-
rite
Arylboronic acids and their derivatives are valuable re-
agents that have been extensively used in cross-coupling
reactions to construct C–C, C–O, C–N and C–X bonds.1 In re-
cent decades many reports have appeared on transition-
metal-catalyzed Suzuki–Miyaura cross-coupling reactions
of arylboronic acids to form biaryls.2 In these reactions,
protodeboronation of the arylboronic acid is a common side
reaction, and was considered to be of no use in organic syn-
thesis; consequently, it attracted little attention. In recent
years, however, the deliberate removal of the –B(OH)2
group has attracted increasing attention, and remarkable
progress has been made. For example, Aggarwal and co-
workers reported enantioselective syntheses of natural or
nonnatural compounds through protodeboronation of allyl-
and/or alkylboronic esters,3,4 which markedly promoted the
application of protodeboronation.
Transition-metal-catalyzed transformation reactions
are widely used in organic synthesis,5 and there have been
several studies on transition-metal-catalyzed protodeboro-
nations of arylboronic acids. As early as in 1930, Ainley and
Challenger reported a protodeboronation with metallic
salts, including CuSO4, CrBr3, and ZnCl2, in organic solvents
at high temperatures.6 Subsequently, Klingensmith et al.
found that phenylboronic acids bearing electron-donating
substituents showed increased rates of protodeboronation
We chose (2,5-dimethoxyphenyl)boronic acid (1a) as a
model substrate to identify the optimal reaction conditions,
and we examined the effects of various transition-metal
catalysts (Cu sources) and of TBAB as an additive (Table 1).
To study the effect of various Cu sources on the protodebor-
onation of arylboronic acids, we performed the reaction in
10.5 wt% aqueous NaClO in the presence of various Cu salts
[CuSO4, CuBr2, Cu(OAc)2, and Cu(OTf)2]. Boronic acid 1a was
converted into 1,4-dimethoxybenzene (2a) in yields of 55,
51, and 56% in the presence of CuSO4, Cu(OAc)2, or Cu(OTf)2,
© 2020. Thieme. All rights reserved. Synlett 2020, 31, A–D
Georg Thieme Verlag KG, Rüdigerstraße 14, 70469 Stuttgart, Germany

B
M. Li et al.
Letter
Synlett
With the optimal reaction conditions in hand, a series of
arylboronic acids were chosen to study the scope of the
protodeboronation. In addition, to study the effects of the
type of substituent group (electron-donating and electron-
withdrawing groups) and the position of substituents (or-
tho or para), the reactions of various arylboronic acids were
examined under the standard reaction conditions. To our
delight, all substituted arylboronic acids gave the corre-
sponding products in good yields in aqueous NaClO (Table
2). From these results, we inferred that the type of substitu-
ent group has little influence on the protodeboronation. For
example, 2,5-(dimethoxyphenyl)boronic acid (1a) and (2-
chlorophenyl)boronic acid (1f) were converted into the cor-
responding products 2a and 2d in yields of 88 and 82%, re-
spectively; (4-morpholin-4-ylphenyl)boronic acid (1h) af-
forded product 2e in 89% yield; and (2-nitrophenyl)boronic
acid (1k) and [2-(trifluoromethyl)phenyl]boronic acid (1l)
gave the corresponding products 2g and 2h in yields of 85
and 83%, respectively.
reported work
Ar B(OH)2
Pd nanoparticles
EtOH
Ar
Ar
H
H
ref. 8
ref. 9
CuSO4, (i-Pr)2NH
Ar B(OH)2
Ar B(OH)2
EtOH/H2O
AgNO3, Et3N
EtOH/H2O
Ar
Ar
H
H
ref. 10
this work
TBAB, NaClO (aq)
Ar B(OH)2
transition-metal-free
base-free
Scheme 1 Protodeboronations of arylboronic acids
respectively (Table 1, entries 1, 3, and 7); however, when
CuBr2 was used, only a trace of 2a was found (entry 5).
When TBAB (20 mol%) was added, the yields of 2a were sig-
nificantly improved (entries 2, 4, 6, and 8); in particular, a
yield of 87% was obtained in the presence of CuSO4 and
TBAB (entry 2). Next, we examined whether a transition-
metal catalyst was necessary. In the absence of both a tran-
sition-metal catalyst and TBAB, the reaction in aqueous
NaClO gave none of the required product (entry 9). Surprising-
ly however, when TBAB alone was added, the yield of 2a in-
creased to 88% (entry 10), which was higher than that ob-
tained under any of the other conditions. Therefore, it was
quite clear that the optimal conditions for protodeborona-
tion of arylboronic acids involve the use of TBAB (20 mol%)
in 10.5 wt% aqueous NaClO at 100 °C for 12 hours.
Table 2 Protodeboronation of Various Arylboronic Acidsa
TBAB
Ar B(OH)2
Ar
H
NaClO (aq)
2
1
Entry
1
1
2
Yieldb (%)
88
B(OH)2
OCH3
H3CO
OCH3
H3CO
2a
1a
Table 1 Optimization of the Protodeboronation of (2,5-Dimethoxy-
phenyl)boronic acid (1a)a
CH3
B(OH)2
CH3
CH3
2
3
4
5
6
84c
72c
90
2b
B(OH)2
1b
[M], additive
H3CO
OCH3
H3CO
OCH3
NaClO (aq)
H3C
B(OH)2
2a
1a
1c
2b
2c
2c
2d
2d
Entry
[M]
Additive
Yieldb (%)
B(OH)2
1
2
CuSO4
CuSO4
–
55
87
51
82
trace
38
56
79
0
TBAB
–
1d
1e
3
Cu(OAc)2
Cu(OAc)2
CuBr2
B(OH)2
86
4
TBAB
–
5
Cl
6
CuBr2
TBAB
–
Cl
82c
7
Cu(OTf)2
Cu(OTf)2
–
B(OH)2
8
TBAB
–
1f
9
Cl
B(OH)2
Cl
N
7
8
74c
89
10
–
TBAB
88
1g
a Reaction conditions: 1a (1 mmol), [M] (0.1 mmol), additive (0.2 mmol),
10.5 wt% aq NaClO (5 mL), 100 °C, 12 h.
b Isolated yield.
O
O
N
B(OH)2
1h
2e
© 2020. Thieme. All rights reserved. Synlett 2020, 31, A–D

C
M. Li et al.
Letter
Synlett
Table 2 (continued)
ran-4-ylboronic acid (1q) gave quinoline (2j) and diben-
zo[b,d]furan (2k) in yields of 87 and 90%, respectively (en-
tries 16 and 17). These results showed that our improved
protocol for protodeboronation of arylboronic acids in wa-
ter is both concise and broadly applicable.
Entry
1
2
Yieldb (%)
90
O
O
B(OH)2
9
H3C
CH3
1i
2f
Based on the results of our study, we propose the mech-
anism shown in Scheme 2 for the NaClO-promoted pro-
todeboronation of arylboronic acids. Initially, the arylbo-
ronic acid undergoes addition of H2O to form an intermedi-
ate arylboronate anion. This is oxidized by NaClO to give the
required product, together with boric acid. In this process,
TBAB acts as a promoter to accelerate the formation of the
arylboronate anion, which leads to the oxidative pro-
todeboronation.
O2N
B(OH)2
NO2
10
11
73
85
1j
2g
NO2
B(OH)2
NO2
2g
2h
1k
1l
CF3
CF3
CF3
12
83
OH
B(OH)2
H2O
NaClO
[O]
ArB(OH)2
B(OH)3
Ar-H
+
Ar
B
OH
OH
Scheme 2 Proposed mechanism for protodeboronation of arylboronic
acids
F3C
B(OH)2
13
14
74
84
1m
2h
2i
B(OH)2
In conclusion, we have developed a concise and practi-
cal method for the protodeboronation of arylboronic acids
under mild conditions in aqueous NaClO.14 This strategy
tolerates a broad scope of arylboronic acids and is low-cost,
transition-metal-free, and base-free.
1n
B(OH)2
15
16
17
91
87
90
2i
1o
1p
Funding Information
B(OH)2
This work was financially supported by the Yunnan Provincial Science
and Technology Department-Applied Basic Research Joint Special
N
O
N
O
2j
Funds of Yunnan University of Chinese Medicine [2017FF117(-023)].
Y
u
n
n
aPnro
v
incSicailenanTcedch
n
o
lo
g
y
D
e
partment(2
0
1
7FF1
1
7(-0
2
3)
B(OH)2
Supporting Information
2k
1q
a Reaction conditions 1 (1 mmol), TBAB (0.2 mmol), 10.5 wt% aq NaClO (5
mL), 100 °C, 6–12 h.
Supporting information for this article is available online at
https://doi.org/10.1055/s-0040-1706298. Su
p
p
ortingInformatio
n
Su
p
p
ortingInformatio
n
b Isolated yield.
c Isolated without column chromatography.
References and Notes
Although arylboronic acids bearing electron-donating
or electron-withdrawing groups were suitable for this reac-
tion system, the position of the substituents had an obvious
effect on protodeboronation. In general, greater steric hin-
drance of the arylboronic acid was beneficial to this reac-
tion. In particular, the yields of ortho-substituted arylbo-
ronic acids (e.g., 1b, 1d, 1f, 1k, and 1l) were higher than
those of their para-substituted counterparts (e.g., 1c, 1e, 1g,
1j, 1m) (Table 2, entries 2–13). Moreover, 2-anthrylboronic
acid (1n) and 9-anthrylboronic acid (1o) gave anthracene
(2i) in yields of 84 and 91%, respectively (entries 14 and 15).
Finally, heterocyclic boronic acids were investigated to
check their susceptibility to the reaction conditions. Pleas-
ingly, quinolin-3-ylboronic acid (1p) and dibenzo[b,d]fu-
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(14) Protodeboronation of Arylboronic Acids; General Procedure
A solution of the appropriate arylboronic acid (1 mmol) and
TBAB (64 mg, 0.2 mmol) in 10.5 wt% aq NaClO was stirred at
100 °C for 6–12 h until the reaction was complete (TLC). The
mixture was extracted with Et2O (2 × 5 mL), and the organic
layer was dried (Na2SO4) and concentrated in vacuo. The residue
was purified by column chromatography [silica gel, PE–EtOAc
(40:1 to 20:1)].
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1,4-Dimethoxybenzene (2a)
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Prepared from 1a according to the general procedure as a white
solid; yield: 121 mg (88%); mp 51–53 °C. 1H NMR (400 MHz,
CDCl3):  = 6.86 (s, 4 H), 3.78 (s, 6 H).
© 2020. Thieme. All rights reserved. Synlett 2020, 31, A–D