Copper-catalyzed regioselective hydroboration of terminal alkynes in aqueous medium

Article abstract of DOI:10.1016/j.tetlet.2016.01.049

A mild and environment-friendly copper-catalyzed hydroboration of terminal alkynes in aqueous medium was reported. Regioselectivity control was achieved in the presence of cyclodextrin-bispyridine ligand (CD-1). This protocol was successfully applied to inactivated terminal alkynes. Moreover, the ligand was recovered and reused without any loss of activity over five cycles.

Full text of DOI:10.1016/j.tetlet.2016.01.049

Tetrahedron Letters xxx (2016) xxx–xxx
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Tetrahedron Letters
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Copper-catalyzed regioselective hydroboration of terminal alkynes in
aqueous medium
a
a
a
a,b,
Zi-Jian Yao a, , Shibin Hong , Wei Zhang , Mengyan Liu , Wei Deng
⇑
⇑
a School of Chemical and Environmental Engineering, Shanghai Institute of Technology, Shanghai 201418, PR China
b Nano-Science & Technology Research Center, Shanghai University, Shanghai 200444, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
A mild and environment-friendly copper-catalyzed hydroboration of terminal alkynes in aqueous med-
ium was reported. Regioselectivity control was achieved in the presence of cyclodextrin–bispyridine
ligand (CD-1). This protocol was successfully applied to inactivated terminal alkynes. Moreover, the
ligand was recovered and reused without any loss of activity over five cycles.
Received 2 December 2015
Revised 12 January 2016
Accepted 13 January 2016
Available online xxxx
Ó 2016 Elsevier Ltd. All rights reserved.
Keywords:
Catalysis
Regioselective
Hydroboration
Aqueous
Recyclable
Cyclodextrin (CD) is a type of extensively used host molecule
competent of guest molecules in aqueous phase. They are often uti-
lized as catalysts in water because of the capacity to dissolve the
hydrophobic compounds and the capability to identify diverse
molecules.1 Among a number of CD derivatives, b-CD has been
broadly used as homogeneous catalysts in various organic reactions.
In our previous work, a series of modified CDs for the construction of
diverse supramolecular systems have been synthesized.2
The CAB bond formation has drawn substantial attention in
recent years.3 Among largely reported methodologies, copper-cat-
alyzed hydroboration reaction is particularly important,4 because
unsaturated substrates and diborons (B2pin2) both involved in this
catalytic process. Recently, a useful copper-catalyzed borylation
has been reported by our group for the preparation of organborons.5
employed in this strategy. A highly regioselective hydroboration
was reported by Yoshida very recently, and their work represented
the first example of
a-hydroboration by the combination of NHC-
Cu catalyst and a masked diboron substrate (Scheme 1C).3k
A
number of branched borylalkenes were synthesized by this facile
Previous work:
Bpin
FG
B2pin2
H
Hoveyda,
(A)
(B)
FG
ref. 6
2009, 2011
FG=OR, NHR
Bpin
R
B2pin2
H
Carretero, 2013
However, the utilization of terminal and a-vinyl(pinacolato)borons
as substrates in this reaction is still limited, and the current meth-
ref. 7
FG
FG
R
ods involve relatively complex requirements.
FG=SO2Py
Hoveyda6 discovered that terminal alkynes could undergo a
highly-selective borylation with B2pin2 in the presence of NHC-
Cu catalyst (Scheme 1A). Carretero7 also have reported a borylation
strategy which relied on the use of a propargylic 2-PySO2 group as
an efficient region-director (Scheme 1B). However, high regioselec-
tivity was obtained only when the substrates with propargyl
amine, propargyl alcohol or propargylic 2-PySO2 group were
B(dan)
R
(pin)B B(dan)
H
R
Yoshida, 2014
(C)
ref. 3k
This work:
Bpin
R
B2pin2
aqeous medium
H
R
(D)
⇑
Corresponding authors. Tel.: +86 21 60877231; fax: +86 21 60873335.
E-mail addresses: zjyao@sit.edu.cn (Z.-J. Yao), wdeng@shu.edu.cn (W. Deng).
Scheme 1. Regiocontrolled borylation of terminal alkynes.
http://dx.doi.org/10.1016/j.tetlet.2016.01.049
0040-4039/Ó 2016 Elsevier Ltd. All rights reserved.
Please cite this article in press as: Yao, Z.-J.; et al. Tetrahedron Lett. (2016), http://dx.doi.org/10.1016/j.tetlet.2016.01.049

2
Z.-J. Yao et al. / Tetrahedron Letters xxx (2016) xxx–xxx
(see in Supporting information). All experiment data revealed that
N
the triazole moiety was bounded to the b-CD unit (Scheme 2).
The coupling reaction between 6-chloro-1-hexyne 1a and
B2pin2 catalyzed by LiOt-Bu in the mixture of toluene and MeOH
was investigated (Table 1, entry 1). Unfortunately the reaction in
water using organic base DBU and catalyst CD-1 did not afford
any product (Table 1, entries 2 and 3). The conversion of 1a was
slightly improved and the product with moderate regioselectivity
N
N
N
N
N
OH
OH
N
click reaction
N
N
OH
(a
/b = 80:20) was obtained when MeOH was added (Table 1, entry
4). It was a delight to observe that the conversion (92%) and the
regioselectivity ( /b = 88:12) both increased when the reaction
L1
O
O
6
OH
OH
a
was catalyzed by CuBr2 at elevated temperature (Table 1, entries
5 and 6). We then optimized the reaction conditions by examining
different bases and found that NaOH was the best choice (Table 1,
entries 7–11). Various copper catalysts were screened in the reac-
tion, and the results revealed that most of them (CuCl2, Cu2O, CuI),
with the exception of Cu(OH)2 and CuSO4, could successfully pro-
mote the catalytic process (Table 1, entries 12–16). The regioselec-
tivity decreased obviously when the reaction was catalyzed by
CuBr2 in the presence of CD or the mixture of CD and L1 (Table 1,
entries 17 and 18). In comparison with the result of entry 18, the
addition of AdNa has little influence on regioselectivity (Table 1,
entry 19). The control experiment of eliminating CD was also per-
formed. Moderate yields and low regioselectivity were obtained
when the reaction was performed in the presence of CuBr2 and
L1 (Table 1, entry 20). Other additives such as SiO2 and tricaprylin,
which can provide hydrophobic environment in aqueous medium,
CD-1
Scheme 2. Synthesis of CD-1.
and efficient method. Herein, a copper-catalyzed hydroboration of
alkynes in aqueous medium is reported. (Scheme 1D). This
approach is the first report of regioselective hydroboration of
alkynes regiocontrolled by cyclodextrin (CD) derivative and it
enables the efficient access to obtain vinyl boronates from simple
terminal alkynes.
The cyclodextrin–bispyridine (CD-1) ligand was prepared in an
almost quantitative yield by click reaction of azide-substituted
cyclodextrin N3-b-CD with L1 in 1:1 molar ratio. The characteristic
peaks of triazole ring were observed in the 1H NMR and 13C NMR
Table 1
Optimization of the reactiona
O
B
O
Cl
3a
4a
β
[Cu], CD-1
Base,Solvent
O
O
O
Cl
+
B
B
+
O
O
O
1a
2a
B
Cl
α
Entry
Cat.
Ligand
Base
T (°C)
Solvent
Yieldb (%)
a
/bb
1
2
3
4
5
6
7
8
None
None
None
None
CuBr2
CuBr2
CuBr2
CuBr2
CuBr2
CuBr2
CuBr2
CuCl2
Cu(OH)2
CuSO4
Cu2O
None
None
CD-1
CD-1
CD-1
CD-1
CD-1
CD-1
CD-1
CD-1
CD-1
CD-1
CD-1
CD-1
CD-1
CD-1
CD+1
CD
LiOt-Bu
DBU
DBU
DBU
DBU
rt
rt
rt
rt
PhMe/MeOH
H2O
H2O
95
10:90
—
—
80:20
81:19
88:12
86:14
93:7
82:18
75:25
84:16
75:25
76:24
81:19
74:26
83:17
35:65
30:70
33:67
36:64
32:68
37:63
Trace
Trace
70
75
92
90
93
90
88
91
92
59
60
91
93
92
91
H2O/MeOH
H2O/MeOH
H2O/MeOH
H2O/MeOH
H2O/MeOH
H2O/MeOH
H2O/MeOH
H2O/MeOH
H2O/MeOH
H2O/MeOH
H2O/MeOH
H2O/MeOH
H2O/MeOH
H2O/MeOH
H2O/MeOH
H2O/MeOH
H2O/MeOH
H2O/MeOH
H2O/MeOH
rt
DBU
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
Na2CO3
NaOH
K2CO3
K3PO4
TEA
NaOH
NaOH
NaOH
NaOH
NaOH
NaOH
NaOH
NaOH
NaOH
NaOH
NaOH
9
10
11
12
13
14
15
16
17
18
19c
20
21d
22
CuI
CuBr2
CuBr2
CuBr2
CuBr2
CuBr2
CuBr2
CD-1
L1
SiO2 + L1
89
71
77
73
Tricaprylin + L1
a
Reactions were carried out using 0.5 mmol 6-chloro-1-hexyne, 1.5 equiv of B2pin2, 10 mmol % catalysts and ligands, 2.0 equiv bases in 2.0 mL of solvent (H2O/
MeOH = 1:1) was stirred at 50 °C for 18 h. The optimization reaction condition was bolded (entry 8).
b
Conversion yield of 1a. Detected by GCMS, pyrene as internal standard.
AdNa was used as additive.
Silica gel (200–300 mesh).
c
d
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Z.-J. Yao et al. / Tetrahedron Letters xxx (2016) xxx–xxx
3
Table 2
Scope of alkynes
O
B
O
R
O
O
CuBr , CD-1
O
O
2
B
+
R
+
B B
NaOH, H O, MeOH
O
R
2
O
o
50 C, 18h
β
α
2a
3b-3x
4b-4x
1a-1x
Alkyl alkynes
Cl
1a
1b
3b+4b 76% yield
1c
1d
3a+4a 93% yield
3c+4c 78% yield
3d+4d 85% yield
α
: β
α
α
α
: β
=
93 : 7
: β
: β
=
60 : 40
=
82 : 18
=
64 : 36
1g
1e
3e+4e 88% yield
1f
1h
3g+4g
3h+4h
3f+4f 70% yield
71% yield
79% yield
α
α
β
α β
α β
:
=65 : 35
β
:
:
:
=
64 : 36
=
93 : 7
=
29 : 71
1i
3i+4i 90% yield
1j
1k
1l
3j+4j 73% yield
3k+4k 54% yield
3l+4l 73% yield
α
β
α
β
α β
α β
:
:
:
:
=
59 : 41
=
54 : 46
=
58 : 42
75 : 25
=
O
O
O
S
1m
1n
1o
3o+4o 69% yield
1p
3p+4p 93% yield
3m+4m 86% yield 3n+4n 45% yield
α
α
β
α
α
: β
:
: β
: β
=
52 : 48
=
69 : 31
=
50 : 50
=50 : 50
Aryl alkynes
Me
F
1r
3r+4r 70% yield
1q
1s
3s+4s 95% yield
1t
3t+4t 87% yield
3q+4q 69% yield
α
α
β
α
α
β
:
β
:
β
:
=
14 : 86
:
=
19 : 81
=
20 : 80
=14 : 86
Cl
Cl
Me
F
1u
3u+4u
1x
55% yield
1v
3v+4v 84% yield
1w
3w+4w
3x+4x
α
: β
79% yield
63% yield
α
α
α
: β
: β
: β
=
14 : 86
=
8 : 92
=
28 : 72
=
29 : 71
were also used in the reaction (Table 1, entries 21 and 22). All
results suggested that CD plays a key role in the reaction.
With optimized reaction conditions in hand (CuBr2/CD-1/NaOH
catalytic system), the hydroboration of various terminal alkynes
was examined. As shown in Table 2, most of the reactions gave
products with good yields and high regioselectivity. The reactions
(ꢀ70%) and regioselectivity (ꢀ60:40) were obtained in most cases
(1h, 1j, 1k), a high yield (up to 90%) was only observed when cyclo-
propylacetylene (1i) was employed in the reaction. The reactivity
of aryl alkynes was also investigated. The results reveal that the
carbon chain between the aryl functional group and alkynyl group
is shorter, the regioselectivity is higher (1l and 1m). The regioselec-
tivity is not good when the alkynes contain the substituted groups
with heteroatoms (1n–p).
of linear alkylalkynes afforded the
a-vinyl(pinacolato)borons in
good to excellent yields (70–93%) (1a–g), but high regioselectivity
was only obtained (93:7) from alkynes with six carbons (1a, 1g).
The steric effects played an important role when alkyl-substituted
alkynes were used as substrates in the reaction. Moderate yields
The reactivity of aryl terminal alkynes was also investigated
under the optimized conditions (Table 2). The reactions of ary-
lalkynes gave worse regioselectivities than those of alkylalkynes,
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Cycle times
Yield (%)
1
2
3
4
5
93
92
90
90
91
a
Reactions condition: optimized condition.
possibly due to the steric hindrance. The reaction between pheny-
lacetylene and diborane afforded the corresponding product in 69%
yield with low regioselectivity (1q). A wide range of para-substi-
tuted aryl terminal alkynes were tested, reactions of 1r–1u with
diborane led to analogous products with similar yields and regios-
electivities. There was no improvement on regioselectivity when
the ortho and meta-substituted arylalkynes were utilized in the
reaction (1v–x).
Encouraged by the results achieved above, we turned our atten-
tion to the reuse of the ligand (CD-1) in hydroboration of alkynes
(Table 3). The use of cyclodextrin ligand made it easy to separate
the product from the reaction mixture by simple extraction. To
our delight, the ligand can be reused for at least fifth cycles without
any loss of activity, which is an obligatory for its practical
application.
In summary, a highly efficient and regioselective method for
alkyne hydroboration in aqueous medium has been developed.
This method provides easy access to a library of borylation com-
pounds from readily available starting materials. The environ-
ment-friendly reaction condition and the reusable feature of the
ligand make this catalytic system very attractive in industrial
applications.
Acknowledgements
This work was supported by the Eastern Scholar, Key Subject of
Shanghai Municipal Education Commission, Shanghai Municipal
Education Commission (Plateau Discipline Construction Program),
National Science Foundation of China (Nos. 21102088 and
21174081), and start funding of Shanghai Institute of Technology.
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Supplementary data
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.tetlet.2016.01.
049.
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Please cite this article in press as: Yao, Z.-J.; et al. Tetrahedron Lett. (2016), http://dx.doi.org/10.1016/j.tetlet.2016.01.049