Acid-promoted metal-free protodeboronation of arylboronic acids

Article abstract of DOI:10.1039/c7ra05979e

A facile acid-promoted protodeboronation of arylboronic acids in the absence of metal catalysts or any other additives is described. This protodeboronation is general for a range of arylboronic acids with both electron-donating and electron-withdrawing groups in good to excellent yields under air atmosphere. Density functional theory mechanistic studies showed that the protodeboronation of arylboronic acids followed an intermolecular metathesis via a four-membered ring transition state. The effect of the substituent of arylboronic acids in protodeboronation is also theoretically studied.

Full text of DOI:10.1039/c7ra05979e

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Acid-promoted metal-free protodeboronation of
arylboronic acids†
Cite this: RSC Adv., 2017, 7, 34959
Guoqing Zhang, Yang Li* and Jianhui Liu *ab
b
ab
A facile acid-promoted protodeboronation of arylboronic acids in the absence of metal catalysts or any
other additives is described. This protodeboronation is general for a range of arylboronic acids with both
electron-donating and electron-withdrawing groups in good to excellent yields under air atmosphere.
Density functional theory mechanistic studies showed that the protodeboronation of arylboronic acids
followed an intermolecular metathesis via a four-membered ring transition state. The effect of the
substituent of arylboronic acids in protodeboronation is also theoretically studied.
Received 28th May 2017
Accepted 5th July 2017
DOI: 10.1039/c7ra05979e
rsc.li/rsc-advances
protodeboronation would be retarded when the arylboronic
acids were substituted with electron-withdrawing groups.
The study about the protodeboronation kinetics by Lloyd-
Introduction
12
Arylboronic acids are versatile precursors in transition metal-
mediated or metal-free cross-coupling reactions to construct Jones showed that the protodeboronation rates were pH-
1
13
C–C, C–N, C–O, and other C–X bonds. They are generally used dependent.
Acid-mediated protodeboronation of allylic
2
4
in the Suzuki–Miyaura cross-coupling reaction and transition boronic esters was reported several years ago. Recently, a mild
metal-catalyzed self-coupling reactions to form (un)symmet- reaction condition for the protodeboronation of arylboronic
3
rical biaryl compounds. However, the protodeboronation of acids, which used AcOH in 1,4-dioxane, was described by
14
arylboronic acids is sometimes a side reaction to compete with Cheon, but only electron-donating groups showed better
Suzuki coupling, due to the strong nucleophilic character of the results. He also reported the metal-free protodeboronation of
arylboronic acids. Compared to the dimerization of arylboronic ortho- and para-phenol boronic acids in wet DMSO under
15
acid, less attention has been paid to the protodeboronation of thermal conditions.
arylboronic acids. The deliberate removal of the –B(OH) that
2
acted as a blocking/directing group in several examples gives
the protodeboronation increased value. For example, Aggarwal
applied the protodeboronation of allylic boronic esters to
Results and discussion
4
In an effort to prepare thiophene 2 in our recent studies of dye-
sensitized solar cells, we found that the standard Knoevenagel
condensation of 5-formyl-2-thiopheneboronic acid (1) with
cyanoacetic acid did not give the expected thiophene 2, but the
protodeboronation product 3 was afforded instead (Scheme 1).
This nding inspired us to investigate the protodeboronation of
other arylboronic acids.
In our attempted Knoevenagel condensation mentioned
above, the protodeboroation product was afforded. Since a good
yield (71%) was obtained, we decided to expand this conversion
to other substrates. The screen of the reaction conditions was
afforded trisubstituted alkenes. The protodeboronation was
also applied by Aggarwal in the asymmetric synthesis to affor-
5
ded tertiary alkyl stereogenic centers, tertiary alcohols and
6
arylethanes. Carre n˜ o reported the signicance of the proto-
deboronation in the regioselective Friedel-Cras alkylation in
7
which –B(OH)
2
played a temporary regiocontroller. Therefore,
the protodeboronation has great application potential in the
organic synthesis and increasing interest has been given to this
research eld.
Although several methods have been reported, mainly
8
including the use of base and/or metal catalysts (Pd/K CO , Cu/
2
3
9
10
isopropamide, Ag/TEA ), acid-mediated protodeboronation
11
has seldom been described,
since the acid-mediated
a
State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian
1
16024, P. R. China. E-mail: zgqdut8023@mail.dlut.edu.cn; chyangli@dlut.edu.cn
b
School of Petroleum and Chemical Engineering, Dalian University of Technology,
Panjin Campus, Panjin, Liaoning Province, 124221, P. R. China
Scheme
1 The unexpected protodeboronation rather than
†
Electronic supplementary information (ESI) available. See DOI:
0.1039/c7ra05979e
condensation.
1
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acid-promoted protodeboronation, except for several cases
ꢀ
where the conversions were conducted at 110 C due to the
lower boiling point of the corresponding protodeboronation
products (Table 2, entries 7–11, for 5g, 5h, 5j). The results are
summarized in Table 2. Electron-donating groups exhibited
a better effect on both rate and yield than electron-withdrawing
groups. The protodeboronation of arylboronic acids with
Scheme 2 Protodeboronation of 5-formyl-2-thiopheneboronic acid.
still required before we started our study. In the original electron-donating groups, such as –OH, –OCH , –Ph, –CH ,
3
3
Knoevenagel, NH OAc was used as a weakly basic catalyst to were completed in 1–4 h with yields between 78–92% (Table 2,
4
capture the reactive hydrogen. In order to check whether entries 1–7). The position of the groups on the phenyl ring had
NH OAc played a role in the protodeboronation, we conducted no obvious effect on the reaction (Table 2, entries 2 vs. 3, 8 vs. 9,
4
a control experiment where 2-formylthiophene (3) was still ob- 10 vs. 11 and 15 vs. 12). In addition, both the arylboronic acid 4d
tained in a yield of 72% without using NH OAc (Scheme 2). This with the strong steric hindrance of two 2-CH O and the poly-
4
3
proved that AcOH alone could promote this reaction and cyclic arylboronic acid 4f could afford excellent yields of 88%
therefore the following studies was performed in AcOH in the and 92% (Table 2, entries 4 and 6). Conversely, as expected,
absence of NH
4
OAc. Although the protodeboronation of orga- electron-withdrawing groups (such as –Br, –Cl, –NO , –COCH ,
2 3
noboronic acid by acids was known, but only with formic acid –CHO, –COOH, –COOCH ), decreased the yield of the proto-
3
16
and several inorganic acids. No systematic studies were found deboronation, furnishing yields of 52–71%, except for 4-Cl
in the literatures using AcOH. In addition, the early study was (85%), 3-COCH (80%) and 4-CHO (84%), in a reaction time of
3
16
focused mainly on the kinetics of the protodeboronation. This 5–20 h (Table 2, entries 8–19). Although no difference was
inspired us to explore a mild and an efficient acid-promoted observed in the yields between weaker electron-withdrawing
protodeboronation universale for various arylboronic acid.
The optimization of reaction conditions for the acid-
mediated protodeboronation was performed rst, and 4-
hydroxyphenylboronic acid (4a) was chosen as a substrate. The
examination of the solvent indicated that acetic acid is the best
acidic medium for the protodeboronation process (yield of
groups such as –Br and –Cl (55–85%) and stronger electron-
a
Table 2 Protodeboronation of arylboronic acids in acetic acid
7
0%), followed by HCOOH with a lower yield of 45%, mixed
solvents of AcOH/H O and HCl/H O with further decreased
yields of no more than 30% (23% and 26%, respectively), and
CF COOH being totally inactive (Table 1, entries 1–5). The
2
2
b
Entry Ar
4-HO–C
Compound Time(h) Product Yield (%)
3
inuence of the temperature was also investigated. As shown in
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
6
H
4
4a
4b
4c
4d
4e
4f
1
4
4
3
3
3
5a
5b
5b
5d
5e
5f
81
84
85
88
83
92
78
55
70
85
71
62
80
52
65
69
84
63
69
66
the same table, the yield of the phenol increased steadily with
4-CH O–C H
3
6
4
4
ꢀ
increasing temperature (Table 1, entries 6–9). Finally, 130 C
3
3-CH O–C
6
H
2,6-(CH
4-Ph–C
9-Anthryl
4-CH –C
3
O)
2
–C
6
H
3
was determined as the best temperature for the reaction.
Under these optimized conditions, different arylboronic
acids were used as substrates to conrm the usefulness of the
6
H
4
c
c
c
c
c
3
6
H
4
4g
4h
4i
3
5
5
5
5g
5h
5h
5j
4-Br–C
3-Br–C
6
H
H
4
6
4
a
0
1
2
3
4
5
6
7
8
9
0
4-Cl–C
3-Cl–C
6
H
H
4
4j
Table 1 Influence of solvent and temperature
6
4
4k
4l
5
10
8
5j
5l
3-NO
3-CH
2
–C
6
H
4
3
CO–C
6
H
H
4
4
4m
4n
4o
4p
4q
4r
5m
5n
5l
5m
5n
5r
3-CHO–C
6
H
4
8
4-NO
4-CH
2
–C
6
H
4
10
16
8
3
CO–C
6
4-CHO–C
4-COOH–C
6 4
H
ꢀ
b
Entry
Solvent
T ( C)
Yield (%)
6
H
4
8
4-CH
2-CH
3
COO–C
COO–C
6
H
4
4s
4t
20
2
5s
5r
1
2
3
4
5
6
7
8
9
AcOH
HCOOH
110
110
110
110
110
25
50
80
130
70
45
23
26
0
d
3
6
H
4
AcOH/H
HCl/H
CF COOH
2
O
O
2
1
4u
2
5u
96
84
2
3
AcOH
AcOH
AcOH
AcOH
8
22
1
2
3
58
63
81
a
Reaction condition: arylboronic acids (0.5 mmol), AcOH (10 mL). The
ꢀ
b
c
reactions were conducted at 130 C under air. Isolated yields. The
a
ꢀ
d
Reaction conditions: arylboronic acids (0.5 mmol), AcOH (10 mL), reactions were conducted at 110 C, GC yields. The product was
b
under air, 1 h. Isolated yields.
benzoic acid rather than the expected methyl benzoate.
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Scheme 5 The proposed mechanism for protodeboronation of aryl-
boronic acids.
Scheme
3 Protodeboronation of 4-hydroxyphenylboronic acid
pinacol ester and potassium 4-carboxyphenyltrifluoroborate.
2 3
withdrawing groups such as –NO , –COCH , –CHO, –COOH and
–
COOCH (52–84%), the reaction rates clearly differed. Proto-
3
deboronation of arylboronic acids with strong electron-
withdrawing groups required longer reaction times of 8–20 h
(
Table 2, entries 12–19). This proved that electron deciency of
the C–B bond did not favor the reaction. Extraordinarily, aryl-
boronic acid substituted with –COOCH on the ortho-position
3
did not give the protodeboronated methyl benzoate, but was
directly hydrolyzed to benzoic acid 5r in just 2 h (Table 2, entry
20). Heterocyclic boronic acids (4u and 1) could also easily
provide the protodeboronation product in excellent yields of
Fig. 1 The energy profiles calculated for the protodeboronation of A1
and A2.
9
2
6% and 84% under these conditions (Table 2, entries 21 and
2). In general, the results above demonstrate the universality of
this reaction.
To further explore the scope of the substrates, the proto-
deboronation of other surrogates such as 4-hydroxyphenylbor-
onic acid pinacol ester (4v) and potassium 4-
carboxyphenyltriuoroborate (4w) were studied. The proto-
deboronation of 4v and 4w still proceeded although longer
reaction time was required (24 h) (Scheme 3). 4v gave the pro-
todeboronation product in a yield of 77%, while 4w affored
a lower yield of 36%. The arylboronic acid pinacol ester and
potassium aryltriuoroborate display enhanced chemical
For the protodeboronation of arylboronic acids, as shown in
Scheme 5, there are two scenarios to address the aryl–H bond
formation: (1) arylboronic acids A react with AcOH to form aryl
complex B via a four-membered ring transition state ATS (path
+
1
); (2) arylboronic acids A can be attack by H reagent to form
ꢁ
complex C, and then OAc attack the –B(OH) motif through
2
B–C bond cleavage and form aryl complex B (path 2). With the
help of DFT calculations, the energy proles of the proto-
deboronation of arylboronic acids are calculated in Fig. 1. Fig. 1
shows that the arylboronic acids react directly with AcOH to
form aryl–H bond via an intermolecular metathesis process. We
failed to locate the complex C in path 2, which means the
complex C is unlikely to be involved as the stable intermediate
in the protodeboronation.
17
stability compared with arylboronic acids. The slower proto-
deboronation rates may be due to the decreased Lewis acidity of
the boron atom from arylboronic acid pinacol ester and potas-
sium aryltriuoroborate, which is consistent with Cheon's
14,15
studies.
Aryl iodides, important building blocks in forming C–C and
C–X (X ¼ heteroatom) bond, are widely used in organic
In order to understand the effect of the substituent of aryl-
boronic acids in protodeboronation, we compared the reaction
proles starting from the arylboronic acids A1 with electron-
donating group (entry 2 in Table 2) and arylboronic acids A2
with electron-withdrawing group (entry 16 in Table 2). From the
energy proles shown in Fig. 1, we can clearly see that proto-
deboronation of A1 (Fig. 1a, with an energy barrier of 37.5 kcal
18
synthesis. As we know, the regioselective iodination of arenes
19
is usually difficult. While the 4-iodoanisole (8) was successfully
formed in a total yield of 61% through the AcOH-promoted
protodeboronation in which the –B(OH) acted as a directing
2
group (Scheme 4).
ꢁ
1
mol ) has lower energy barrier than that of A2 (Fig. 1b, with an
ꢁ
1
energy barrier of 43.4 kcal mol ). Electronically, the boron-
bonded carbon in A1 is electron-rich when compared with
that in A2 because of the electron property of substituent of
arylboronic acids. The natural bond orbital (NBO) analysis
shows that the natural atomic charges of the boron-bonded
carbon are calculated to be ꢁ0.468 in A1 and ꢁ0.409 in A2,
respectively, suggesting that the AcOH reagent favors attack of
Scheme 4 The protodeboronation of arylboronic acid was applied in
the synthesis of 4-iodoanisole.
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the boron-bonded carbon in A1 over that in A2. These results are
consistent with the experimental observation that arylboronic
acids with electron-donating group have high yield with short
reaction time than that with electron-withdrawing group.
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5
In conclusion, we have achieved an acid-mediated proto-
deboronation from a wide variety of arylboronic acid substrates.
Compared to other methods reported before, it is a greener
process in that no any metal catalysts and additives are needed.
The only use of acetic acid is highly practical. In addition, the
electron-withdrawing groups can also be tolerated in the pro-
todeboronation. This method could be an attractive comple-
ment to the case in which substituents of the arylboronic acids
are susceptible to alkaline medium. An intermolecular
metathesis reaction mechanism was developed based on DFT
calculations. Additionally, the NBO analysis provided informa-
tion on the effect of the substituent of arylboronic acids.
6
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2
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The nancial support of this study was from the State Key
Laboratory of Fine Chemicals (Panjin) (Grant No. JH2014009)
project and the Fundamental Research Funds for the Central
Universities. Professor Yang Li thanks the Scientic Research
Foundation of Dalian University of Technology (Grant No.
DUT16RC(3)037) and Supercomputing Center of Dalian
University of Technology for providing access to the
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34962 | RSC Adv., 2017, 7, 34959–34962
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