Borane-Catalysed Hydroboration of Alkynes and Alkenes

Article abstract of DOI:10.1055/s-0036-1591719

Simple, commercially available borane adducts, H ₃ B·THF and H ₃ B·SMe ₂, have been used to catalyse the hydroboration of alkynes and alkenes with pinacolborane to give the alkenyl and alkyl boronic esters, respectively. A

Full text of DOI:10.1055/s-0036-1591719

SYNTHESIS
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© Georg Thieme Verlag Stuttgart · New York
2017, 49, A–F
paper
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en
N. W. J. Ang et al.
Paper
Synthesis
Borane-Catalysed Hydroboration of Alkynes and Alkenes
Nate W. J. Ang
H
Bpin
R2
H3B⋅THF
R2
H
Bpin
+
R1
or
Cornelia S. Buettner
Scott Docherty
R1
H3B⋅SMe2
(10 mol%)
anti-Markovnikov
18 examples
dr >98:2
- alkynes and alkenes
- commercially available borane catalyst
- highly regio- and diastereoselective
Alessandro Bismuto
Jonathan R. Carney
Jamie H. Docherty
Michael J. Cowley
Stephen P. Thomas*
0
0
0
0
0-
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0
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8-
6
1
4
2-
9
4
7
EaStCHEM School of Chemistry, Joseph Black Building,
University of Edinburgh, David Brewster Road,
Edinburgh, EH9 3FJ, UK
Stephen.Thomas@ed.ac.uk
Published as part of the Bürgenstock Special Section 2017 Future Stars in Organic Chemistry
Received: 04.09.2017
Accepted after revision: 10.10.2017
Published online: 20.11.2017
hydroboration has also been proposed in the titanium- and
calcium-catalysed addition of catechol borane to
alkynes.18,19 However, and to the best of our knowledge, a
simple borane has not been used to catalyse the hydrobora-
tion of alkynes or alkenes. Herein, we report the direct hyd-
roboration of alkynes and alkenes with HBpin using either
of the commercially available borane adducts, H3B·THF or
H3B·SMe2, as the catalyst (Scheme 1, C).
DOI: 10.1055/s-0036-1591719; Art ID: ss-2017-z0575-op
Abstract Simple, commercially available borane adducts, H3B·THF and
H3B·SMe2, have been used to catalyse the hydroboration of alkynes and
alkenes with pinacolborane to give the alkenyl and alkyl boronic esters,
respectively. Alkynes and terminal alkenes underwent highly regiose-
lective hydroboration to give the linear boronic ester products. Good
functional group tolerance was observed for substrates bearing ester,
amine, ether and halide substituents. This catalytic process shows com-
parable reactivity to transition-metal-catalysed hydroboration proto-
cols.
A Transition-metal-catalysed hydroboration of olefins
H
B(OR)2
R2
R2
H
B(OR)2
TM
+
R1
R1
Key words borane, hydroboration, alkynes, alkenes, main-group, ca-
talysis
TM = Rh, Fe, Co, Mn, Ti
B Main-group-catalysed hydroboration of olefins
Boronic esters are powerful synthetic intermediates
that have found widespread use and act as precursors for an
array of transformations.1,2 The hydroboration of alkynes
and alkenes offers the simplest route to boronic esters;
however, and unlike boranes, boronic esters do not readily
undergo olefin hydroboration. Most commonly a second- or
third-row transition-metal catalyst is needed for the direct
hydroboration of olefins with boronic esters.3 However, the
increasing need for sustainable chemical processes has led
to a drive for first-row transition metal4–7 (Scheme 1, A) and
main-group catalyst alternatives (Scheme 1, B).8–17 Al-
though alkyne hydroboration has been achieved using bo-
ron-derived catalysts,9–15 to our knowledge, there is only a
single report of a boron-catalysed alkene hydroboration.12
Oestreich and co-workers used the highly Lewis acid tris(3-
H
Bpin
R2
R2
+
H Bpin
MG
R1
R1
MG = [Al], HBCy2, [NHC(B-9-BBN)]+,
HB(C6F5)2, BArF3, 2,4,6-BArF
3
C This work: Borane-catalysed hydroboration of olefins
H
Bpin
R2
R2
+
H Bpin
B
R1
R1
B = H3B⋅THF
or
H3B⋅SMe2
Scheme 1 (A) Transition-metal-catalysed hydroboration of olefins. (B)
Main-group-catalysed hydroboration of olefins. (C) This work: borane-
catalysed hydroboration of olefins.
5-trifluoromethylphenyl)borane, BArF , to catalyse the di-
3
rect addition of pinacolborane, HBpin, to alkenes.12 Here,
the active catalyst was generated by ligand metathesis be-
Our investigations began by testing commercially avail-
able solutions of H3B·THF (1.0 M in THF) and H3B·SMe2 (ca.
10 M in SMe2) for catalytic competency in the hydrobora-
tion of phenylacetylene and 4-tert-butylstyrene with HBpin
(Table 1). Borane dimethyl sulphide showed low catalytic
activity at room temperature (Table 1, entries 1 and 4). In-
tween BArF and HBpin to generate a borane that under-
3
went alkene hydroboration and another ligand metathesis
with HBpin to give the product boronic ester and regener-
ate the borane catalyst. A catalytic role for boranes in olefin
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–F

B
N. W. J. Ang et al.
Paper
Synthesis
creasing the reaction temperature to 60 °C led to successful
catalysis by both borane adducts in only 30 minutes for the
hydroboration of phenylacetylene, which gave the linear
alkenyl boronic ester 2a in good yield, regio- and diastereo-
selectivity (entries 2 and 3). Significantly, both borane ad-
ducts successfully catalysed the hydroboration of 4-tert-
butylstyrene to give the alkyl boronic ester in good yield
and regioselectivity (entries 5 and 6). During the prepara-
tion of this manuscript Wu, Liu, Zhao and co-workers re-
ported the hydroxide-catalysed hydroboration of olefins
and proposed a catalytically active borohydride intermedi-
ate.20 Thus, we trialled hydridic boron reagents as cata-
lysts,21,22 but decreased reactivity was observed in all cases
(entries 7–10). Importantly, in the absence of a borane cata-
lyst, only trace hydroboration was observed for both the
alkyne and alkene substrates (entries 11–12).
an ester substituent 2f were tolerated without the observa-
tion of detrimental side reactions, albeit with decreased
product yields, presumably by coordination and inhibition
of the borane catalyst.
H3B·THF
H
Bpin
R2
(1 M in THF, 10 mol%)
60 °C
R2
+
H Bpin
R1
R1
1a–r
2a–r
H
H
H
Bpin
Bpin
Bpin
MeO
Et
2a
2b
2c
93%
72%
73%
H
H
H
Bpin
Bpin
Bpin
O
F
H2N
Table 1 Catalyst Identificationa
MeO
2d
2e
2f
94%
51%
26%
H
[B]
H
H
Bpin
+
H
H
R
Bpin
temperature
R
Bpin
Ph
Bpin
Cl
Bpin
n-Hex
1
2
2h
2g
77%
2i
84%
91% (92:8)a
Entry
Cat (10 mol%)
Substrate
T (°C)
Yield (%)b
H
1
2
H3B·SMe2
H3B·THF
H3B·SMe2
H3B·SMe2
H3B·THF
H3B·SMe2
NaHBEt3
phenylacetylene
phenylacetylene
phenylacetylene
4-tert-butylstyrene
4-tert-butylstyrene
4-tert-butylstyrene
phenylacetylene
phenylacetylene
4-tert-butylstyrene
4-tert-butylstyrene
phenylacetylene
4-tert-butylstyrene
25
60
60
25
60
60
60
60
60
60
60
60
19c
76
75
5c
H
H
Bpin
Bpin
Bpin
3
2l
2j
85%
2k
81%
4
64% (75:25)b
5
84
83
45
50
40
17
–
H
H
H
6
Bpin
Bpin
Bpin
Bpin
(EtO)3Si
n-Hex
Ph
7
2m
75%
2n
73%
2o
68%
8
Na(CH3COO)3BH
9
NaHBEt3
H
H
H
Bpin
Bpin
10
11
12
Na(CH3COO)3BH
–
–
MeO
F
–
2p
2q
2r
67%
84%
78%
a Reaction conditions: olefin (1 equiv), catalyst (10 mol%), pinacolborane
(1.25 equiv), t = 30 min (alkyne) or 18 h (alkene).
Scheme 2 Substrate scope for the H3B·THF-catalysed hydroboration of
alkynes and alkenes. Reagents and conditions: olefin (1 equiv), H3B·THF
(1.0 M in THF, 10 mol%), HBpin (1.1 equiv) at 60 °C for 1 h (alkynes) or
18 h (alkenes). Yields are reported as isolated yield. Regio- and diastereo-
selectivity >98:2. a As a mixture of regioisomers (E:Z 92:8). b A mixture
of regioisomers were obtained with (Linear:Branched 75:25).
b Yield was determined by 1H NMR spectroscopy using 1,3,5-trimethoxy-
benzene as an internal standard.
c Reaction mixtures were stirred for 18 h at 25 °C.
Using optimised reaction conditions23 of H3B·THF (1.0 M
in THF, 10 mol%) and HBpin (1.1 equivalents) at 60 °C in no
additional solvent for one hour, we investigated the sub-
strate scope of this hydroboration (Scheme 2). Terminal
alkynes underwent hydroboration to give the linear (E)-
alkenyl boronic esters with excellent control of regioselec-
tivity and diastereoselectivity (2a–k). Aryl-substituted
alkynes bearing electron-donating alkyl 2b or ether 2c
groups and an electron-withdrawing fluoro substituent 2d
all underwent successful hydroboration in good yield and
without loss of regioselectivity. A free amine 2e and even
Alkyl-substituted alkynes were also successful sub-
strates in this hydroboration, again giving the linear (E)-
alkenyl boronic esters with excellent control of regioselec-
tivity and diastereoselectivity (2g–k). Primary 2g–i, sec-
ondary 2j and tertiary 2k alkyl substitution had little effect
on catalyst activity and regioselectivity, with only the ben-
zyl substituted alkyne 2h showing a slight decrease in re-
giocontrol. Even an internal alkyne underwent hydrobora-
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–F

C
N. W. J. Ang et al.
Paper
Synthesis
tion to give the (Z)-alkenyl boronic ester 2l with moderate
regioselectivity for addition of the boron group at the least
sterically encumbered carbon.
ringes. These syringes were flushed prior to use. In addition, all glass-
ware was cleaned in a base bath (KOH/iPrOH) and acid (aq HCl) bath;
rinsed with acetone and dried in an oven at 180 °C.
All the borane sources were commercially available and used without
further purification. Solvents were dried over sodium/benzophenone
and distilled under pure argon atmosphere. C6D6 and toluene-d8 were
dried over potassium and distilled under nitrogen atmosphere. NMR
We next turned our attention to terminal alkenes
(Scheme 2, 2m–r). Although a longer reaction time (18
hours) was required for this substrate class compared with
alkynes, alkyl- 2m–o and aryl-substituted 2p–r alkenes all
successfully underwent hydroboration with complete con-
trol of the regioselectivity of addition to give the linear bo-
ronic esters. Once again, electron-donating 2p,q and elec-
tron-withdrawing 2r aryl substituents gave equal reactivity.
Given that BH3 was capable of catalysing the hydrobora-
tion of olefins, we questioned whether nucleophile-pro-
moted decomposition of HBpin22,24 would facilitate this
same olefin hydroboration reaction. Therefore, we trialled
using alkoxide salts as reagents to generate BH3 in situ, from
HBpin, that would subsequently undergo hydroboration
with the present olefin. The use of LiOtBu as an initiative
catalyst in combination with HBpin and alkynes 1a or 1g at
60 °C successfully gave the alkyne hydroboration products
2a and 2g in excellent yields and with complete control of
both diastereoselectivity and regioselectivity (>95% and
67%, Scheme 3).
Spectra were recorded with Bruker PRO 500 MHz (1H 500.2 MHz, 11
B
160.5 MHz, 13C 125.8 MHz, 19F NMR 471 MHz, 29Si NMR 99 MHz), AVA
500 (1H 500.1 MHz, 2H 500.2 MHz, 13C 125.8 MHz) or AVA 600 (1H
600.8 MHz, 13C 151.1 MHz) spectrometers. 1H and 13C NMR peaks
were referenced to residual solvent signals 1H NMR: δ (ppm) = 7.26
(CDCl3), 7.15 (C6D6), 7.09 (toluene-d8), 5.32 (CD2Cl2), 1.72 (THF-d8);
13C NMR: δ (ppm) = 53.84 (CD2Cl2), 67.21 (THF-d8), 77.16 (CDCl3),
128.06 (C6D6), 137.48 (toluene-d8).
Flash column chromatography was performed on silica gel (Merck
Kielselgel 60, 40–63 μm) and product spots were visualised by UV
light at 254 nm or by oxidising with KMnO4. Short columns were pre-
pared using a Braun Injekt 10 mL syringe of diameter 0.6 inches with
a Luer Lock.
Pinalcolborane 3 (HBpin) Cat N 010818 was purchased from Fluo-
rochem. All other reagents were purchased from Sigma–Aldrich, Alfa
Aesar, Acros Organics, Tokyo Chemical Industries UK and Fluorochem,
and were used without further purification. Specifically, the borane
sources, H3B·THF; H3B·SMe2, H-B-9-BBN, NaBH4, NaHBEt3 were ob-
tained from Sigma–Aldrich and Na(CH3COO)3BH was obtained from
Acros Organics.
H
Bpin
(E)-4,4,5,5-Tetramethyl-2-(phenyl-1-enyl)-1,3,2-dioxaborolane
(2a); General Procedure A
LiOtBu (10 mol%)
1a
1g
>95%
or
2a
Phenylacetylene (1.00 mmol, 0.110 mL), pinacolborane (1.10 mmol,
0.160 mL) and H3B·THF (0.100 mmol, 1 M, 0.100 mL) were added se-
quentially to a sealed reaction vial flushed with an nitrogen atmo-
sphere. The reaction mixture was stirred for 1 h at 60 °C. The reaction
was then quenched by filtration through a short silica plug (5 cm)
with CH2Cl2. The solvents were removed under reduced pressure and
the residue was purified by flash column chromatography (SiO2; hex-
ane/EtOAc, 98:2), to give the boronic ester 2a (215.1 mg, 0.93 mmol,
93%) as a colourless oil.
+
H
Bpin
or
n-Hex
neat
20 h, 60 °C
(1.5 equiv)
H
Bpin
n-Hex
67%
2g
Scheme 3 Use of an alkoxide salt as an initiative catalyst for alkyne hy-
droboration. Yields were determined by 1H NMR spectroscopy using
1,3,5-trimethoxybenzene as internal standard.
1H NMR (500 MHz, CDCl3): δ = 7.52–7.47 (m, 2 H), 7.41 (d, J = 18.4 Hz,
1 H), 7.36–7.27 (m, 3 H), 6.18 (d, J = 18.4 Hz, 1 H), 1.32 (s, 12 H).
13C NMR (126 MHz, CDCl3): δ = 149.6, 137.6, 129.0, 128.7, 127.2,
116.4 (br, C-B), 83.5, 25.0.
11B NMR (160 MHz, CDCl3): δ = 29.87.
In summary, we have developed a BH3-catalysed hyd-
roboration of alkynes and alkenes with pinacolborane to
give alkenyl- and alkyl pinacol boronic esters in good yield
and with excellent control of both regio- and diastereose-
lectivity. Using commercially available borane adducts,
H3B·THF and H3B·SMe2, terminal alkynes and alkenes un-
derwent direct hydroboration with HBpin to give the bo-
ronic ester products in synthetically useful yield. Detailed
mechanistic studies are ongoing and will be reported in due
course.
Procedure for Alkoxide-Initiated Hydroboration of Alkynes
Phenylacetylene (1.00 mmol, 0.110 mL) or 1-octyne (1.00 mmol,
0.148 mL), pinacolborane (1.50 mmol, 0.218 mL) and LiOtBu (0.100
mmol, 8.00 mg) were added sequentially into a sealed reaction vial
flushed with nitrogen. The reaction mixture was stirred for 20 h at
60 °C. The reaction was cooled to r.t., then Et2O (2.00 mL) and distilled
H2O (1.00 mL) were added and the organic layer was extracted. The
yield was determined by adding 1,3,5-trimethoxybenzene (0.10
mmol, 16.8 mg) as internal standard.
All manipulations were carried out under a nitrogen atmosphere us-
ing Schlenk techniques or in an inert atmosphere glovebox. All reac-
tion apparatus including flasks, if not otherwise specified, were evac-
uated, heated with a heat-gun and purged with nitrogen three times.
Liquid reagents were added with septum and single-use plastic sy-
(E)-4,4,5,5-Tetramethyl-2-(4-ethylphenyl-1-enyl)-1,3,2-dioxaboro-
lane (2b)
According to General Procedure A, 4-ethylphenylacetylene (1.00
mmol, 0.140 mL), pinacolborane (1.10 mmol, 0.160 mL), and H3B·THF
(0.100 mmol, 1 M, 0.100 mL) were reacted for 1 h. The residue was
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–F

D
N. W. J. Ang et al.
Paper
Synthesis
purified by flash column chromatography (SiO2; hexane/EtOAc 98:2),
Methyl 4-[(E)-2-(4,4,5,5-Tetramethyl-2-yl)ethenyl]benzoate-1,3,2-
to give boronic ester 2b (184.7 mg, 0.720 mmol, 72%) as a colourless
dioxaborolane (2f)
oil.
According to General Procedure A, methyl 4-ethynylbenzoate (1.00
mmol, 0.160 g), pinacolborane (1.10 mmol, 0.160 mL), and H3B·THF
(0.100 mmol, 1 M, 0.100 mL) were reacted for 1 h. The residue was
purified by flash column chromatography (SiO2; hexane/EtOAc, 98:2),
to give boronic ester 2f (74.7 mg, 0.260 mmol, 26%) as an amorphous
pale-yellow powder; mp 95.6–97.4 °C (hexane/EtOAc).
1H NMR (500 MHz, CDCl3): δ = 8.11–7.90 (m, 2 H), 7.55–7.52 (m, 2 H),
7.41 (d, J = 18.4 Hz, 1 H), 6.27 (d, J = 18.4 Hz, 1 H), 3.91 (s, 3 H), 1.32 (s,
12 H).
1H NMR (500 MHz, CDCl3): δ = 7.43–7.41 (m, 2 H), 7.39 (d, J = 18.2 Hz,
1 H), 7.18–7.16 (m, 2 H), 6.12 (d, J = 18.4 Hz, 1 H), 2.65 (q, J = 7.6 Hz,
2 H), 1.32 (s, 12 H), 1.23 (t, J = 7.6 Hz, 3 H).
13C NMR (126 MHz, CDCl3): δ = 149.6, 145.4, 135.2, 128.2, 127.2,
115.4 (br C-B), 83.4, 28.8, 25.0, 15.5.
11B NMR (160 MHz, CDCl3): δ = 29.93.
(E)-4,4,5,5-Tetramethyl-2-(4-methoxyphenyl-1-enyl)-1,3,2-dioxa-
borolane (2c)
13C NMR (126 MHz, CDCl3): δ = 166.9, 148.3, 141.9, 130.1, 129.7,
127.0, 119.5 (br C-B), 83.7, 52.3, 25.0.
11B NMR (160 MHz, CDCl3): δ = 29.68.
According to General Procedure A, 4-ethylnylanisole (1.00 mmol,
0.130 mL), pinacolborane (1.10 mmol, 0.160 mL), and H3B·THF (0.100
mmol, 1 M, 0.100 mL) were reacted for 1 h. The residue was purified
with flash column chromatography (SiO2; hexane/EtOAc, 98:2), to
give boronic ester 2c (188.5 mg, 0.730 mmol, 73%) as a colourless oil.
1H NMR (500 MHz, CDCl3): δ = 7.43–7.41 (m, 2 H), 7.39 (d, J = 18.2 Hz,
1 H), 7.18–7.16 (m, 2 H), 6.12 (d, J = 18.4 Hz, 1 H), 2.65 (q, J = 7.6 Hz,
2 H), 1.32 (s, 12 H), 1.23 (t, J = 7.6 Hz, 3 H).
13C NMR (126 MHz, CDCl3): δ = 149.6, 145.4, 135.2, 128.2, 127.2,
115.4 (br C-B), 83.4, 28.8, 25.0, 15.5.
11B NMR (160 MHz, CDCl3): δ = 29.93.
(E)-4,4,5,5-Tetramethyl-2-(oct-1-enyl)-1,3,2-dioxaborolane (2g)
According to General Procedure A, 1-octyne (1.00 mmol, 0.148 mL),
pinacolborane (1.10 mmol, 0.160 mL), and H3B·THF (0.100 mmol, 1 M,
0.100 mL) were reacted for 1 h. The residue was purified by flash col-
umn chromatography (SiO2; hexane/EtOAc 98:2), to give boronic ester
2g (183.3 mg, 0.770 mmol, 77%) as a colourless oil.
1H NMR (500 MHz, CDCl3): δ = 6.63 (dt, J = 17.9, 6.4 Hz, 1 H), 5.42 (dt,
J = 18.0, 1.6 Hz, 1 H), 2.14 (td, J = 7.9, 1.6 Hz, 2 H), 1.46–1.36 (m, 3 H),
1.33–1.20 (m, 14 H), 0.91–0.85 (m, 6 H).
13C NMR (126 MHz, CDCl3): δ = 155.0, 118.8 (br C-B), 83.1, 36.0, 31.9,
29.1, 28.4, 24.9, 22.7, 14.2.
11B NMR (160 MHz, CDCl3): δ = 29.69.
(E)-4,4,5,5-Tetramethyl-2-(4-fluorophenyl-1-enyl)-1,3,2-dioxa-
borolane (2d)
According to General Procedure A, 4-fluorophenylacetylene (1.00
mmol, 0.115 mL), pinacolborane (1.10 mmol, 0.160 mL), and H3B·THF
(0.100 mmol, 1 M, 0.100 mL) were reacted for 1 h. The residue was
purified by flash column chromatography (SiO2; hexane/EtOAc, 98:2),
to give boronic ester 2d (232.5 mg, 0.940 mmol, 94%) as colourless
needles; mp 63.5–65.3 °C (hexane/EtOAc) (Lit.25 62–63 °C).
1H NMR (500 MHz, CDCl3): δ = 7.50–7.42 (m, 2 H), 7.35 (d, J = 18.4 Hz,
1 H), 7.06–6.98 (m, 2 H), 6.07 (d, J = 18.5 Hz, 1 H), 1.31 (s, 12 H).
13C NMR (126 MHz, CDCl3): δ = 163.3 (d, JC–F = 248.6 Hz), 148.3, 133.9
(d, J = 3.3 Hz), 128.9 (d, J = 8.4 Hz), 115.7 (d, J = 21.7 Hz), 83.5, 25.0.
(E)-4,4,5,5-Tetramethyl-2-(3-phenylpropy-1-enyl)-1,3,2-dioxa-
borolane (2h)
According to General Procedure A, 3-phenyl-1-propyne (1.00 mmol,
0.124 mL), pinacolborane (1.10 mmol, 0.160 mL), and H3B·THF (0.100
mmol, 1 M, 0.100 mL) were reacted for 1 h. The residue was purified
with flash column chromatography (SiO2; hexane/EtOAc, 98:2), to
give boronic ester 2h [223.2 mg, 0.910 mmol, 91% (92a+8b)] as a co-
lourless oil. The product was isolated as a mixture of regioisomers
(a+b).
1H NMR (500 MHz, CDCl3): δ (major isomer) = 7.33–7.27 (m, 2 H),
7.24–7.16 (m, 3 H), 6.79 (dt, J = 17.9, 6.3 Hz, 1 H), 5.47 (d, J = 17.9,
1 H), 3.50 (d, J = 6.4, 2 H), 1.27 (s, 12 H).
11B NMR (160 MHz, CDCl3): δ = 29.80.
19F NMR (471 MHz, CDCl3): δ = 112.46 (m).
(E)-4,4,5,5-Tetramethyl-2-(4-aminophenyl-1-enyl)-1,3,2-dioxa-
borolane (2e)
13C NMR (126 MHz, CDCl3): δ = 152.6, 139.2, 129.1, 128.6, 126.3,
120.0 (br C-B), 83.2, 42.4, 24.9.
According to General Procedure A, 4-aminophenylacetylene (1.00
mmol, 0.117 g), pinacolborane (1.10 mmol, 0.160 mL), and H3B·THF
(0.100 mmol, 1 M, 0.100 mL) were reacted for 1 h. The residue was
purified by flash column chromatography (SiO2; CH2Cl2/MeOH, 99:1),
to give boronic ester 2e (124.2 mg, 0.510 mmol, 51%) as yellow
prisms.
1H NMR (500 MHz, CDCl3): δ = 7.37–7.26 (m, 3 H), 6.67–6.57 (m, 2 H),
5.93 (d, J = 18.3 Hz, 1 H), 3.78 (s, 2 H), 1.30 (s, 12 H).
13C NMR (126 MHz, CDCl3): δ = 149.7, 147.5, 128.7, 128.4, 115.0,
11B NMR (160 MHz, CDCl3): δ = 29.49.
(E)-4,4,5,5-Tetramethyl-2-(5-chloropent-1-enyl)-1,3,2-dioxaboro-
lane (2i)
According to General Procedure A, 5-chloro-1-pentyne (1.00 mmol,
0.106 mL), pinacolborane (1.10 mmol, 0.160 mL), and H3B·THF (0.100
mmol, 1 M, 0.100 mL) were reacted for 1 h. The residue was purified
by flash column chromatography (SiO2; hexane/EtOAc, 98:2), to give
boronic ester 2i (193.3 mg, 0.840 mmol, 84%) as a colourless oil.
1H NMR (500 MHz, CDCl3): δ = 6.58 (dt, J = 18.0, 6.4 Hz, 1 H), 5.48 (dt,
J = 18.0, 1.6 Hz, 1 H), 3.53 (t, J = 6.7 Hz, 2 H), 2.33–2.27 (m, 2 H), 1.93–
1.86 (m, 2 H), 1.26 (s, 12 H).
111.8 (br C-B), 83.2, 25.0.
11B NMR (160 MHz, CDCl3): δ = 29.91.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–F

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N. W. J. Ang et al.
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Synthesis
13C NMR (126 MHz, CDCl3): δ = 152.2, 120.2 (br C-B), 83.3, 44.5, 32.9,
11B NMR (160 MHz, CDCl3): δ = 33.96.
31.2, 24.9.
11B NMR (160 MHz, CDCl3): δ = 29.39.
4,4,5,5-Tetramethyl-2-(4-phenyl-1-butyl)-1,3,2-dioxaborolane
(2n)
According to General Procedure A, 4-phenyl-1-butene (1.00 mmol,
0.150 mL), pinacolborane (1.10 mmol, 0.160 mL), and H3B·THF (0.100
mmol, 1 M, 0.100 mL) were reacted for 18 h. The residue was purified
by flash column chromatography (SiO2; hexane/EtOAc, 98:2), to give
boronic ester 2n (188.7 mg, 0.730 mmol, 73%) as a colourless oil.
1H NMR (500 MHz, CDCl3): δ = 7.29–7.24 (m, 2 H), 7.20–7.14 (m, 3 H),
2.63–2.58 (m, 2 H), 1.68–1.59 (m, 2 H), 1.53–1.44 (m, 2 H), 1.25 (s,
12 H), 0.82 (t, J = 7.8 Hz, 2 H).
(E)-4,4,5,5-Tetramethyl-2-(cyclopropyl-1-enyl)-1,3,2-dioxaboro-
lane (2j)
According to General Procedure A, cyclopropylacetylene (1.00 mmol,
0.085 mL), pinacolborane (1.10 mmol, 0.160 mL), and H3B·THF (0.100
mmol, 1 M, 0.100 mL) were reacted for 1 h. The residue was purified
by flash column chromatography (SiO2; hexane/EtOAc, 98:2), to give
boronic ester 2j (164.3 mg, 0.850 mmol, 85%) as a colourless oil.
1H NMR (500 MHz, CDCl3): δ = 6.09 (ddd, J = 17.8, 9.3, 1.1 Hz, 1 H),
5.50 (d, J = 17.8 Hz, 1 H), 1.58–1.49 (m, 1 H), 1.27 (s, 12 H), 0.84–0.79
(m, 2 H), 0.57–0.52 (m, 2 H).
13C NMR (126 MHz, CDCl3): δ = 143.1, 128.5, 128.3, 125.6, 83.0, 35.9,
34.3, 25.0, 23.9, 11.3 (br C-B).
13C NMR (126 MHz, CDCl3): δ = 158.7, 115.4 (br C-B), 83.1, 25.0, 17.1,
11B NMR (160 MHz, CDCl3): δ = 33.94.
8.0.
11B NMR (160 MHz, CDCl3): δ = 29.51.
4,4,5,5-Tetramethyl-2-(3-(triethoxysilyl)propyl)-1,3,2-dioxaboro-
lane (2o)
According to General Procedure A, allyltriethoxysilane (1.00 mmol,
0.226 mL), pinacolborane (1.10 mmol, 0.160 mL), and H3B·THF (0.100
mmol, 1 M, 0.100 mL) were reacted for 18 h. The residue was purified
by flash column chromatography (SiO2; hexane/EtOAc, 98:2), to give
boronic ester 2o (215.2 mg, 0.680 mmol, 68%) as a colourless oil.
1H NMR (500 MHz, CDCl3): δ = 3.80 (q, J = 7.0 Hz, 6 H), 1.59–1.50 (m,
2 H), 1.24–1.19 (m, 21 H), 0.85 (t, J = 7.6 Hz, 2 H), 0.70–0.64 (m, 2 H).
13C NMR (126 MHz, CDCl3): δ = 83.0, 58.4, 25.0, 18.4, 17.6, 15.3 (br C-
B), 13.5.
11B NMR (160 MHz, CDCl3): δ = 33.83.
29Si NMR (99 MHz, CDCl3): δ = 45.02.
(E)-4,4,5,5-Tetramethyl-2-(3,3-dimethyl-but-1-enyl)-1,3,2-dioxa-
borolane (2k)
According to General Procedure A, 3,3-dimethyl-1-butyne (1.00
mmol, 0.122 mL), pinacolborane (1.10 mmol, 0.160 mL), and H3B·THF
(0.100 mmol, 1 M, 0.100 mL) were reacted for 1 h. The residue was
purified by flash column chromatography (SiO2; hexane/EtOAc, 98:2),
to give boronic ester 2k (170.5 mg, 0.810 mmol, 81%) as a viscous co-
lourless oil.
1H NMR (500 MHz, CDCl3): δ = 6.64 (d, J = 18.3 Hz, 1 H), 5.35 (d,
J = 18.3 Hz, 1 H), 1.27 (s, 12 H), 1.02 (s, 9 H).
13C NMR (126 MHz, CDCl3): δ = 164.6, 112.5 (br C-B), 83.1, 35.2, 29.0,
25.0.
11B NMR (160 MHz, CDCl3): δ = 30.23.
4,4,5,5-Tetramethyl-2-(4-methoxyphenyl-1-ethyl)-1,3,2-dioxa-
borolane (2p)
(Z)-4,4,5,5-Tetramethyl-2-(1-phenyl(prop-1-en)-2-yl)-1,3,2-dioxa-
borolane (2l)
According to General Procedure A, 4-methoxystyrene (1.00 mmol,
0.133 mL), pinacolborane (1.10 mmol, 0.160 mL), and H3B·THF (0.100
mmol, 1 M, 0.100 mL) were reacted for 18 h. The residue was purified
by flash column chromatography (SiO2; hexane/EtOAc, 98:2), to give
boronic ester 2p (175.3 mg, 0.670 mmol, 67%) as a colourless oil.
1H NMR (500 MHz, CDCl3): δ = 7.17–7.10 (m, 2 H), 6.84–6.77 (m, 2 H),
3.78 (s, 3 H), 2.73–2.66 (m, 2 H), 1.22 (s, 12 H), 1.15–1.08 (m, 2 H).
13C NMR (126 MHz, CDCl3): δ = 157.7, 136.7, 129.0, 113.7, 83.2, 55.4,
29.2, 25.0, 13.3 (br C-B).
11B NMR (160 MHz, CDCl3): δ = 33.64.
According to General Procedure A, 1-phenyl-1-propyne (1.00 mmol,
0.125 mL), pinacolborane (1.10 mmol, 0.160 mL), and H3B·THF (0.100
mmol, 1 M, 0.100 mL) were reacted for 1 h. The residue was purified
by flash column chromatography (SiO2; hexane/EtOAc, 98:2), to give
boronic ester 2l (156.2 mg, 0.640 mmol, 64% (75a+25b)) as a colourless
oil. The product was isolated as a mixture of regioisomers (a+b).
1H NMR (500 MHz, CDCl3): δ (major isomer) = 7.41–7.30 (m, 4 H),
7.27–7.14 (m, 2 H), 2.00 (d, J = 1.7 Hz, 3 H), 1.77 (m, 3 H), 1.32 (s,
12 H), 1.27 (s, 9 H).
13C NMR (126 MHz, CDCl3): δ = 142.8, 142.5, 140.0, 138.1, 129.5,
129.2, 128.2, 127.9, 127.2, 126.0, 83.7, 25.0, 24.9, 16.1, 16.0.
11B NMR (160 MHz, CDCl3): δ = 30.23.
4,4,5,5-Tetramethyl-2-(4-tert-butylphenyl-1-ethyl)-1,3,2-dioxa-
borolane (2q)
According to General Procedure A, 4-tert-butylstyrene (1.00 mmol,
0.183 mL), pinacolborane (1.10 mmol, 0.160 mL), and H3B·THF (0.100
mmol, 1 M, 0.100 mL) were reacted for 18 h. The residue was purified
by flash column chromatography (SiO2; hexane/EtOAc, 98:2), to give
boronic ester 2q (195.3 mg, 0.840 mmol, 84%) as a colourless oil.
1H NMR (500 MHz, CDCl3): δ = 7.30–7.27 (m, 2 H), 7.17–7.13 (m, 2 H),
2.76–2.67 (m, 2 H), 1.30 (s, 9 H), 1.22 (s, 12 H), 1.17–1.11 (m, 2 H).
13C NMR (126 MHz, CDCl3): δ = 148.4, 141.5, 127.8, 125.2, 83.2, 34.5,
31.6, 29.5, 25.0, 13.1 (br C-B).
11B NMR (160 MHz, CDCl3): δ = 33.66.
4,4,5,5-Tetramethyl-2-(octyl)-1,3,2-dioxaborolane (2m)
According to General Procedure A, 1-octene (1.00 mmol, 0.157 mL),
pinacolborane (1.10 mmol, 0.160 mL), and H3B·THF (0.100 mmol, 1 M,
0.100 mL) were reacted for 18 h. The residue was purified by flash
column chromatography (SiO2; hexane/EtOAc, 98:2), to give boronic
ester 2m (180.2 mg, 0.750 mmol, 75%) as a colourless oil.
1H NMR (500 MHz, CDCl3): δ = 1.45–1.38 (m, 2 H), 1.32–1.25 (m,
10 H), 1.24 (s, 12 H), 0.87 (t, J = 6.9 Hz, 3 H), 0.76 (t, J = 7.8 Hz, 2 H).
13C NMR (126 MHz, CDCl3): δ = 83.0, 32.6, 32.1, 29.5, 29.4, 25.0, 24.2,
22.8, 14.3, 11.1 (br C-B).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–F

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N. W. J. Ang et al.
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Synthesis
4,4,5,5-Tetramethyl-2-(4-fluorophenyl-1-ethyl)-1,3,2-dioxaboro-
lane (2r)
(5) Zhang, L.; Zuo, Z.; Leng, X.; Huang, Z. Angew. Chem. Int. Ed. 2014,
53, 2696.
(6) Zhang, G.; Zeng, H.; Wu, J.; Yin, Z.; Zheng, S.; Fettinger, J. C.
Angew. Chem. Int. Ed. 2016, 55, 14369.
(7) He, X.; Hartwig, J. F. J. Am. Chem. Soc. 1996, 118, 1696.
(8) Tucker, C. E.; Davidson, J.; Knochel, P. J. Org. Chem. 1992, 57,
3482.
According to General Procedure A, 4-fluorostyrene (1.00 mmol, 0.119
mL), pinacolborane (1.10 mmol, 0.160 mL), and H3B·THF (0.100 mmol,
1 M, 0.100 mL) were reacted for 18 h. The residue was purified by
flash column chromatography (SiO2; hexane/EtOAc, 98:2), to give bo-
ronic ester 2r (193.7 mg, 0.780 mmol, 78%) as a colourless oil.
(9) Shirakawa, K.; Arase, A.; Hoshi, M. Synthesis 2004, 1814.
(10) McGough, J. S.; Butler, S. M.; Cade, I. A.; Ingleson, M. J. Chem. Sci.
2016, 7, 3384.
(11) Fleige, M.; Möbus, J.; vom Stein, T.; Glorius, F.; Stephan, D. W.
Chem. Commun. 2016, 10830.
1H NMR (500 MHz, CDCl3): δ = 7.21–7.11 (m, 2 H), 6.99–6.87 (m, 2 H),
2.72 (t, J = 8.1 Hz, 2 H), 1.21 (s, 12 H), 1.15–1.09 (m, 2 H).
13C NMR (126 MHz, CDCl3): δ = 161.2 (d, JC–F = 242.5 Hz), 140.1 (d,
J = 3.1 Hz), 129.5 (d, J = 7.6 Hz), 115.0 (d, J = 21.0 Hz), 83.3, 29.3, 25.0,
13.3 (br C-B).
(12) Yin, Q.; Kemper, S.; Klare, H. F. T.; Oestreich, M. Chem. Eur. J.
2016, 22, 13840.
11B NMR (160 MHz, CDCl3): δ = 33.48.
(13) Lawson, J. R.; Wilkins, L. C.; Melen, R. L. Chem. Eur. J. 2017, 23,
10997.
19F NMR (471 MHz, CDCl3): δ = 118.43 (tt, J = 9.5, 4.0 Hz).
(14) Barbeyron, R.; Benedetti, E.; Cossy, J.; Vasseur, J.-J.; Arseniyadis,
S.; Smietana, M. Tetrahedron 2014, 70, 8431.
(15) Lawson, J. R.; Melen, R. L. Inorg. Chem. 2017, 56, 8627.
(16) Bismuto, A.; Thomas, S. P.; Cowley, M. J. Angew. Chem. Int. Ed.
2016, 55, 15356.
(17) Fasano, V.; Curless, L. D.; Radcliffe, J. E.; Ingleson, M. J. Angew.
Chem. Int. Ed. 2017, 56, 9202.
(18) Burgess, K.; van der Donk, W. A. Organometallics 1994, 13, 3616.
(19) Harder, S.; Spielmann, J. J. Organomet. Chem. 2012, 698, 7.
(20) Wu, Y.; Shang, C.; Ying, J.; Su, J.; Zhu, J.; Liu, L. L.; Zhao, Y. Green
Chem. 2017, 19, 4169.
Acknowledgment
S.P.T. thanks the Royal Society for a University Research Fellowship.
Both M.J.C. and S.P.T. thank the University of Edinburgh for funding.
All thank the EPSRC and CRITICAT CDT for financial support (Ph.D.
studentship to A.B.; EP/L016419/1).
Supporting Information
(21) Zaranek, M.; Witomska, S.; Patroniak, V.; Pawluć, P. Chem.
Commun. 2017, 5404.
(22) Query, I. P.; Squier, P. A.; Larson, E. M.; Isley, N. A.; Clark, T. B.
J. Org. Chem. 2011, 76, 6452.
Supporting information for this article is available online at
https://doi.org/10.1055/s-0036-1591719.
S
u
p
p
ortiInfogrmoaitn
S
u
p
p
ortioInfgrmoaitn
(23) See the Supporting Information for details of reaction optimisa-
tion
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© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–F