Microwave-assisted, Ir-catalyzed aromatic C-H borylation

Article abstract of DOI:10.1007/s11164-012-0725-4

One-step conversions of 1,3-disubstituted benzenes to aryl boronates and 2,6-disubstituted pyridines to heteroaryl boronates are described. Microwave heating was used for all reactions. [(COD)Ir(μ-OMe)]₂ and 4,4′-di-tert-butyl-2,2′-bipyridine w

Full text of DOI:10.1007/s11164-012-0725-4

Res Chem Intermed (2013) 39:1917–1926
DOI 10.1007/s11164-012-0725-4
Microwave-assisted, Ir-catalyzed aromatic
C–H borylation
•
Li Zeqing Liang Zhibin Wang Yuqiang Yu Pei
•
•
Received: 3 May 2012 / Accepted: 8 July 2012 / Published online: 21 July 2012
Ó Springer Science+Business Media B.V. 2012
Abstract One-step conversions of 1,3-disubstituted benzenes to aryl boronates
and 2,6-disubstituted pyridines to heteroaryl boronates are described. Microwave
heating was used for all reactions. [(COD)Ir(l-OMe)]2 and 4,40-di-tert-butyl-2,20-
bipyridine were used as catalysts, in methyl tert-butyl ether. Acceleration of the rate
of reaction was remarkable compared with that of same reaction under conventional
heating conditions.
Keyword Microwave heating ꢀ [(COD)Ir(l-OMe)]2 ꢀ Dtbpy ꢀ Pinacol boronates
Introduction
The aryl boronates, important intermediates in organic synthesis, have been widely
used in many useful transformations including Suzukui–Miyaura cross coupling
reactions [1], Cu-catalyzed C–O and C–N coupling reactions [2], and Rh-catalyzed
conjugate additions to carbonyl compounds [3, 4]. Pinacol boronates, prepared by
converting aryl halides to aryl boronates by use of bis(pinacolato)diboron, are their
common precursors. The conversion is catalyzed by Pd [5]. Although this method is
widely used, it is unsuitable for polyhalogen-substituted compounds. To solve this
problem, Hartwig performed C–H borylation of benzene with Re and Rh as catalysts
[6, 7]. Later Smith demonstrated aromatic borylation with Hartwig’s Rh catalyst
[8, 9].
L. Zeqing ꢀ L. Zhibin ꢀ W. Yuqiang ꢀ Y. Pei
College of Pharmacy, Institute of New Drug Research, Jinan University, Guangzhou 510632, China
W. Yuqiang ꢀ Y. Pei (&)
Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drug
Research, Guangzhou 510632, China
e-mail: 304969759@qq.com
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L. Zeqing et al.
In recent years, this problem has been overcome by use of Ir-catalyzed C–H
borylation, in which the halogen remains on the aromatic heterocyclic compound
even when the reactant is an aryl halide. The most widely applied system is
[(COD)Ir(l-OMe)]2 with 4,40-di-tert-butyl-2,20-bipyridine (dtbpy) [10]. Some
results suggest that the intermediate [Ir(Bpin)3L2] (Bpin = B(OCMe2CMe2O)) is
the active complex for C–H activation. This intermediate is a five-membered ring
and steric hindrance could contribute to increasing the selectivity of the reaction
[11].
The synthesis of aryl boronates by Ir-catalyzed borylation of arenes has been
reported [12–16]. However, improvement for preparation of aryl boronates, for
example acceleration of the reactions, has not received much attention. In this work,
a series of 1,3-disubstituted benzenes and 2,6-disubstituted pyridines were used as
reactants for synthesis of pinacol boronates under microwave heating and
conventional heating conditions. The effect on yield of factors such as reaction
time, solvent, substituent groups, and electronic and steric effects were investigated
systematically. It was found that microwave irradiation substantially accelerated the
Ir-catalyzed borylation of aromatic and heterocyclic compounds.
It is generally agreed that the enhanced rate of reaction is a purely thermody-
namic effect in most cases [17]. In other words, reaction time will be reduced if a
high reaction temperature can be achieved in a short time. Unlike conventional
heating, microwave irradiation does not transfer energy to the reaction system
through the vessel. It induces very efficient internal heating of the molecules
(solvents, reagents, and catalysts) without heating the vessel surface. A solvent
which absorbs microwave energy with high efficiency, for example methanol, can
be rapidly superheated even above its boiling point when heated under microwave
conditions in a sealed vessel. Such a solvent can provide a large amount of energy in
a short time to accelerate the reaction.
Results and discussion
Tamura et al. [18] have already given a theoretical elucidation of the catalytic cycle
of Ir-catalyzed borylation of benzene with diboron. Use of [(COD)Ir(l-OMe)]2 with
dtbpy as catalyst was believed to be the most efficient system. In this work, selection
of the solvent was further investigated.
Reaction of compound 1 (1,3-dimethoxybenzene), as typical reactant, in different
solvents was catalyzed by [(COD)Ir(l-OMe)]2 and dtbpy (Scheme 1; Table 1). All
reactions were carried out with 1,3-dimethoxybenzene (1 mmol), B2pin2
(1.1 mmol), [Ir(OMe)cod]2 (1.5 mmol %), dtbpy (3.0 mmol %), and solvent
(2.4 mL) in a microwave heating reactor at 80 °C for 1 h [19].
The results indicated that methyl tert-butyl ether (MTBE) is the most effective
solvent, which is consistent with a previous report [20] (Table 1). This may be
because of the better solubility of the reactant in MBTE than in other solvents.
A series of 1,3-disubstituted benzenes were chosen as reactants to prepare
pinacol boronates under conventional heating and microwave irradiation conditions
(Scheme 2; Table 2).
123

Ir catalyzed aromatic C–H borylation
1919
O
O
O
[Ir(OMe)cod]/dtbpy
B2pin2
O
O
O
O
O
O
)
(B2pin2=
B
B
B
o
µ
80 C, W, solvent
O
60 min
1a
1
Scheme 1 Reaction of 1,3-dimethoxybenzene with B2pin2 catalyzed by [Ir(OMe)cod]2 and dtbpy under
microwave conditions
Table 1 Synthesis of 1a in different solvents
Entry
Solvent
Catalyst
Ligand
Time (min)
Temperature (°C)
Yield (%)
1
1
1
1
1
THF
[(COD)Ir(l-OMe)]2
[(COD)Ir(l-OMe)]2
[(COD)Ir(l-OMe)]2
[(COD)Ir(l-OMe)]2
[(COD)Ir(l-OMe)]2
dtbpy
dtbpy
dtbpy
dtbpy
dtbpy
60
60
60
60
60
80
80
80
80
80
75
64
78
90
80
DMF
Dioxane
MTBE
Hexane
All reactions were conducted with 1,3-dimethoxybenzene (1 mmol), B2pin2 (1.1 mmol), [Ir(OMe)cod]2
(1.5 mmol %), dtbpy (3.0 mmol %), and solvent (2.4 mL) in a microwave heating reactor
R1
R1
[Ir(OMe)cod]2/dtbpy
B2pin2
O
O
B
80 oC,µW, MTBE
60 min
R2
R2
Scheme 2 Reaction of 1,3-disubstituted benzenes with B2pin2 catalyzed by [Ir(OMe)cod]2 and dtbpy at
80 °C
Under conventional heating conditions, complete conversion for entry 1 in
Table 2 required 80 °C for 8 h and strict N2 atmosphere [21]. Also, the
concentrations of catalyst and substrate had to be higher than for microwave
heating [22], otherwise the yield might be substantially reduced. In contrast, it took
only 60 min to complete the conversion for entry 1 under microwave irradiation,
even though the amounts of catalyst and ligand were half those under conventional
heating conditions. In addition, a higher yield was achieved under microwave
irradiation than with conventional heating. Similar results were observed for entry 2.
The reaction time was significantly reduced under microwave irradiation.
Asymmetric 1,3-disubstituted benzenes (entries 3–13 in Table 2) were used as
reactants with microwave heating at 80 °C for 30 or 60 min. All reaction conditions
were similar except for the different starting material. GC–MS was used to monitor
the amount of reactant remaining. An important aspect of this kind of reaction is the
selectivity of conversion of asymmetric 1,3-disubstituted benzenes into aryl
boronates. The starting materials in entries 3–7 are bromo-substituted and meta-
123

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L. Zeqing et al.
Table 2 Microwave-assisted Ir-catalyzed borylation of disubstituted benzenes
Entry
R1
R2
Product
Microwave heating
Standard heating
Time (min)
Yielda (%)
Time (min)
Yielda (%)
1
2
OMe
OMe
Cl
1a
1b
1c
1d
1e
1f
60
60
30
30
60
60
60
60
60
60
60
60
60
90
94
84
91
77
75
84
80
85
73
81
82
85
480
720
87
93
82
88
79
73
85
83
80
69
84
84
80
Cl
3
Me
Br
480
4
CH(CH3)2
OMe
Br
480
5
Br
1,080
960
6
OEt
Br
7
OCH2C(OEt)2
OMe
Br
1g
1h
1i
1,080
1,080
1,080
900
8
Cl
9
Me
CN
F
10
11
12
13
a
CF3
1j
OMe
CN
I
1k
1l
1,080
480
COOMe
Me
CHO
1m
360
Purified isolated yield of reaction achieving 100 % conversion
group compounds. The large size of the substituent group leads to steric hindrance.
The results showed that the steric hindrance and the electron-donating groups
contributed to the improved yield. Product 1c was synthesized by the microwave
method for the first time, i.e. it is a new compound. The starting materials for entries
5–7 are derivatives of 3-bromophenol, whose hydroxyl groups were all protected. If
the phenols had been unprotected, the active proton may have deactivated the
catalyst. The reaction in entry 5 required 16 h to complete according to a literature
report [23]; with microwave heating only 1 h was needed. Products 1f and 1g were
also synthesized for the first time by this method. These results suggest that the
scope of application might be dramatically increased by use of appropriate
protective groups.
The reaction time for entries 8, 9 and 11 was also substantially shortened, from
18 to 1 h, by use of microwaves.
The reactant in entry 10 is well known; it was difficult to convert completely.
This might be because of the fluorine atom—because of its electron-donating effect
and weak steric hindrance. By analysis of the GC–MS data, it was found that the
purity of compound 1j was approximately 86.1 %. For entry 12 the yield was 80 %
when the reagents were heated at 80 °C for 8 h in MTBE; microwave heating
afforded 82 % within 1 h.
This was the first synthesis of compound 1m (entry 13), a boronate which
contains an aldehyde group. This result suggested that the active proton of the
aldehyde did not affect the Ir catalyst.
1
According to the H NMR spectra of the products in Table 2, all of the pinacol
boronates were located at C-5. This result suggested the method has high selectivity
123

Ir catalyzed aromatic C–H borylation
1921
R1
N
R1
N
[Ir(OMe)cod2]/dtbpy
B2pin2
O
O
B
80 oC, µW, MTBE
R2
30-60 min
R2
Scheme 3 Reaction of 2,6-disubstituted pyridines with B2pin2 catalyzed by [Ir(OMe)cod]2 and dtbpy at
80 °C
Table 3 Microwave-assisted Ir-catalyzed borylation of disubstituted pyridines
Entry
R1
R2
Product
Microwave heating
Standard heating
Time (min)
Yielda (%)
Time (min)
Yielda (%)
14
15
16
17
18
19
20
a
Br
Br
2n
2o
2p
2q
2r
2s
5
5
95
98
88
90
85
90
79
30
30
94
95
80
88
80
83
75
Me
Me
C(CH3)3
C(CH3)3
Me
C(CH3)3
COOMe
Cl
30
30
30
30
30
480
480
900
480
900
CF3
Cl
OMe
Cl
2t
Purified isolated yield of reaction achieving 100 % conversion
for both symmetric and asymmetric 1,3-disubstituted arenes. The main reason for
this result might be that the less hindered location was substituted selectively.
To further validate this method, a series of 2,6-disubstituted pyridines were
selected as reactants (Scheme 3). As is apparent from Table 3, reaction time was
dramatically reduced by microwave heating compared with conventional heating. In
Table 3, the starting materials in entries 14 and 15 were completely converted in
5 min, in agreement with a literature report [24]. Because of the high polarity, the
products were difficult to separate from B2pin2 and a small amount of dimer
remained in the products. The starting materials in entries 16 and 17 were highly
sterically hindered, which led to excellent selectivity. The reaction took only 30 min
to give compounds 2p (88 % yield) and 2q (90 % yield). The starting materials in
entries 18–20 contained a chlorine atom and were also converted to compounds 2r,
2s, and 2t with excellent yields.
Further comparison of the results in Tables 2 and 3 revealed that the reaction
time was shorter when substituted pyridines were used as reactants [25]. Because
pyridine derivatives coordinate extremely strongly with Lewis acids, the Ir metal or
the boron atom binds reversibly to the basic nitrogen.
Conclusions
In summary, an efficient, highly selective, and environmental friendly method has
been developed for iridium-catalyzed borylation of 1,3-disubstituted benzenes and
2,6-disubstituted pyridines. This borylation reaction proceeded much more quickly
123

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L. Zeqing et al.
when microwave irradiation, rather than conventional heating, was used. In addition,
because of the affinity of the basic nitrogen in pyridine for the Ir catalyst, the reaction
time for pyridine borylation was significant shorter than for benzene borylation.
Compounds 1d, 1g, 1l, 1m, 2p, and 2q have not been reported previously, i.e.
they are all new compounds. The other known compounds except 2o have been
synthesized previously by conventional methods. In this work, microwave
irradiation significantly accelerated the reaction rate and resulted in a higher yield
than conventional heating.
In particular, compound 1m is the first pinacol boronate containing an aldehyde
group to be synthesized successfully by use of iridium as catalyst and microwave
heating. In general, if a substrate contains an active proton, the catalyst is
deactivated. For this reason, the active proton must be protected during borylation.
To our surprise, 1m was synthesized without such protection. To extend the range of
substrates other heterocyclic compounds, for example indoles, furans, pyrroles and
thiophenes, are being investigated.
Experimental
All starting materials were purchased from commercial sources. Reactions were
carried out in identical thick-walled glass reaction tubes with crimp-top septum
seals. 1H NMR and 13C spectra were recorded on a Bruker 400 MHz spectrometer in
CDCl3 or DMSO-d6 using TMS as internal standard. The reactions were monitored
at regular intervals by GC–MS to measure conversion and for product identification.
A mixture of the substrate (1 mmol), [(COD)Ir(l-OMe)]2 (1.5 mmol.%), dtbpy
(3.0 mmol.%), and B2pin2 (1.1 mmol) was dissolved in MTBE (2.4 mL) and the
solution was heated at 80 °C for 60 min by microwave irradiation until GC–MS
analysis indicated the starting material was consumed completely. The mixture was
washed with water and extracted with ethyl acetate (EA; 15 mL 9 3). The
combined extracts were dried with anhydrous MgSO4 and the solvent was removed
in vacuo. The product was purified by chromatography over silica gel.
A mixture of the substrate (1 mmol), [(COD)Ir(l-OMe)]2 (3.0 mmol.%), dtbpy
(6.0 mmol.%) and B2pin2 (1.1 mmol) was dissolved in MTBE (5.0 mL) and the
solution was then heated at 80 °C overnight under N2. Analysis by GC–MS indicated
the starting material was consumed completely. The mixture was washed with water
and extracted with EA (15 mL 9 3). Combined extracts were dried with anhydrous
MgSO4 and the solvent was removed in vacuo. The product was purified by
chromatography over silica gel.
Spectroscopic data for representative products
2-(3,5-Dimethoxyphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (1a)
1H NMR (400 MHz, CDCl3) (d, ppm): 1.34 (12H, s, CH3), 3.81 (6H, s, OCH3), 6.56
(1H, t, J = 2.4 Hz, ArH), 6.95 (2H, t, J = 2.4 Hz, ArH); 13C NMR (400 MHz,
123

Ir catalyzed aromatic C–H borylation
1923
CDCl3) (d, ppm): 24.87, 55.44, 83.90, 104.54, 111.58, 160.38; GC–MS (EI): m/
z = 264.1 [M]?.
2-(3,5-Didichlorophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (1b)
1H NMR (400 MHz, CDCl3) (d, ppm): 1.34 (12H, s, CH3), 7.43 (1H, t, J = 2.0 Hz,
ArH), 7.65 (2H, t, J = 2.0 Hz, ArH); 13C NMR (400 MHz, CDCl3) (d, ppm): 23.81,
83.48, 130.04, 131.68, 133.68; GC–MS (EI): m/z = 257.0 [M - 15]?.
2-(3-Bromo-5-methylphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (1c)
1H NMR (400 MHz, DMSO-d6) (d, ppm): 1.29 (12H, s, CH3), 3.32 (3H, s, CH3),
7.47 (1H, s, ArH), 7.54 (2H, t, J = 2.4 Hz, ArH); 13C NMR (400 MHz, DMSO-d6)
(d, ppm): 20.28, 24.53, 83.94, 121.47, 133.49, 133.78, 140.10; GC–MS (EI): m/
z = 281.0 [M - 15]?.
2-(3-Bromo-5-isopropylphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (1d)
1H NMR (400 MHz, DMSO-d6) (d, ppm): 1.19 (6H, d, J = 7.2 Hz, CH3), 1.29
(12H, s, CH3), 2.92 (1H, m, CH), 7.49 (1H, s, ArH), 7.57 (1H, d, J = 5.2 Hz, ArH),
7.58 (1H, d, J = 6.0 Hz, ArH); 13C NMR (400 MHz, DMSO-d6) (d, ppm): 24.11,
25.11, 33.62, 84.55, 122.31, 131.54, 132.65, 134.63, 151.50; GC–MS (EI): m/
z = 309.1 [M - 15]?.
2-(3-Bromo-5-methoxyphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (1e)
1H NMR (400 MHz, CDCl3) (d, ppm): 1.34 (12H, s, CH3), 3.81 (3H, s, OCH3), 6.99
(1H, s, ArH), 7.15 (1H, s, ArH), 7.23 (1H, s, ArH), 7.52 (1H, d, J = 1.2 Hz, ArH);
13C NMR (400 MHz, CDCl3) (d, ppm):19.61, 50.31, 78.96, 112.72, 115.37, 117.45,
124.52, 154.68; GC–MS (EI): m/z = 312.1 [M]?.
2-(3-Bromo-5-ethoxyphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (1f)
1H NMR (400 MHz, CDCl3) (d, ppm): 1.33 (12H, s, CH3), 1.39 (3H, t, J = 6.8 Hz,
CH3), 4.04 (2H, t, J = 6.8 Hz, OCH2), 7.14 (1H, t, J = 2.0 Hz, ArH), 7.23 (1H, d,
J = 2.0 Hz, ArH), 7.50 (1H, d, J = 0.8 Hz, ArH); 13C NMR (400 MHz, CDCl3) (d,
ppm): 9.52, 19.61, 58.57, 78.92, 113.44, 115.84, 117.42, 124.35, 154.05; GC–MS
(EI): m/z = 326.1 [M]?.
2-(3-Bromo-5-(2,2-diethoxyethoxy)phenyl)-4,4,5,5-tetramethyl-1,3,2-
dioxaborolane (1g)
1H NMR (400 MHz, CDCl3) (d, ppm): 1.25 (6H, t, J = 7.2 Hz, CH3),1.33 (12H, s,
CH3), 3.63 (2H, q, J = 7.2 Hz, OCH2), 3.76 (2H, q, J = 7.2 Hz, OCH2), 4.01 (2H,
d, J = 5.2 Hz, OCH2), 4.81 (2H, d, J = 5.2 Hz, OCH2), 7.18 (1H, t, J = 2.0 Hz,
ArH), 7.26 (1H, d, J = 2.0 Hz, ArH), 7.52 (1H, d, J = 1.6 Hz, ArH); 13C NMR
123

1924
L. Zeqing et al.
(400 MHz, CDCl3) (d, ppm): 15.34, 24.85, 62.66, 68.85, 84.20, 100.42, 118.67,
121.33, 122.64, 130.08, 158.90; GC–MS (EI): m/z = 399.1 [M - 15]?.
2-(3-Chloro-5-methoxyphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (1h)
1H NMR (400 MHz, CDCl3) (d, ppm): 1.34 (12H, s, CH3), 3.82 (3H, s, OCH3), 6.99
(1H, s, ArH), 7.19 (1H, d, J = 2.4 Hz, ArH), 7.37 (1H, d, J = 1.6 Hz, ArH); 13C
NMR (400 MHz, CDCl3) (d, ppm): 24.88, 55.58, 84.22, 117.48, 117.77, 126.90,
134.63, 159.94; GC–MS (EI): m/z = 268.1 [M]?.
3-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzonitrile (1i)
1H NMR (400 MHz, CDCl3) (d, ppm): 1.35 (12H, s, CH3), 2.39 (3H, s, CH3), 7.53
(1H, s, ArH), 7.82 (1H, s, ArH), 7.89 (1H, s, ArH); 13C NMR (400 MHz, CDCl3) (d,
ppm): 20.98, 24.88, 84.44, 111.98, 119.02, 134.79, 135.60, 138.39, 139.62; GC–MS
(EI): m/z = 228.1 [M - 15]?.
2-(3-Fluoro-5-(trifluoromethyl)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane
(1j)
1H NMR (400 MHz, CDCl3) (d, ppm): 1.36 (12H, s, CH3), 7.29 (1H, d, J = 9.2 Hz
ArH), 7.40 (1H, d, J = 6.8 Hz, ArH), 7.85 (1H, d, J = 6.0 Hz, ArH); 13C NMR
(400 MHz, CDCl3) (d, ppm): 19.58, 79.38, 115.05, 119.34, 129.97, 132.42, 160.22,
162.73; 19F NMR (400 MHz, CDCl3) (d, ppm): -100.64, -63.14; GC–MS (EI): m/
z = 275.1 [M - 15]?.
3-Methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzonitrile (1k)
1H NMR (400 MHz, CDCl3) (d, ppm): 1.35 (12H, s, CH3), 3.85 (3H, s, OCH3), 7.21
(1H, q, J = 1.2 Hz, ArH), 7.52 (1H, d, J = 2.8 Hz, ArH), 7.67 (1H, s, ArH); 13C
NMR (400 MHz, CDCl3) (d, ppm):19.61, 50.37, 79.28, 107.67,113.43, 114.72,
118.91, 125.38, 153.86; GC–MS (EI): m/z = 244.1 [M - 15]?.
Methyl 3-iodo-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate (1l)
1H NMR (400 MHz, CDCl3) (d, ppm): 1.35 (12H, s, CH3), 3.92 (3H, s, OCH3), 8.30
(1H, d, J = 0.4 Hz, ArH), 8.40 (1H, s, ArH), 8.45 (1H, t, J = 1.6 Hz, ArH); 13C
NMR (400 MHz, CDCl3) (d, ppm): 24.87, 52.32, 84.47, 93.95, 131.47, 134.77,
140.93, 147.6242, 165.70; GC–MS (EI): m/z = 388.1 [M]?.
3-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzaldehyde (1m)
1H NMR (400 MHz, CDCl3) (d, ppm): 1.27 (12H, s, CH3), 2.44 (3H, s, CH3), 8.30
(1H, d, J = 0.4 Hz, ArH), 7.44 (1H, d, J = 1.2 Hz, ArH), 7.55 (1H, d,
J = 10.4 Hz, ArH), 7.69 (1H, s, ArH), 9.99 (1H, s, CHO); 13C NMR (400 MHz,
123

Ir catalyzed aromatic C–H borylation
1925
CDCl3) (d, ppm): 21.24, 35.04, 83.53, 127.26, 128.90, 130.04, 135.31, 136.46,
138.93, 192.67; GC–MS (EI): m/z = 239.2 [M - 15]?.
2,6-Dibromo-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (2n)
1H NMR (400 MHz, CDCl3) (d, ppm): 1.26 (12H, s, CH3), 7.45 (2H, m, ArH); 13
C
NMR (400 MHz, CDCl3) (d, ppm): 25.05, 83.51, 127.07, 140.09, 140.91; GC–MS
(EI): m/z = 363.1 [M]?.
2,6-Di-tert-butyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (2o)
1H NMR (400 MHz, CDCl3) (d, ppm): 1.35 (18H, s, CH3), 1.36 (12H, s, CH3), 7.44
(2H, s, ArH); 13C NMR (400 MHz, CDCl3) (d, ppm): 24.87, 30.23, 37.63, 84.09,
120.30, 166.88; GC–MS (EI): m/z = 303.3.1 [M - 15]?.
Methyl 6-(tert-butyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)picolinate
(2p)
1H NMR (400 MHz, CDCl3) (d, ppm): 1.37 (12H, s, CH3), 1.41 (9H, s, CH3), 3.97
(3H, s, OCH3), 7.85 (1H, d, J = 0.4 Hz, ArH), 8.24 (1H, d, J = 0.8 Hz, ArH); 13
C
NMR (400 MHz, CDCl3) (d, ppm): 24.74, 30.21, 52.65, 84.63, 127.70, 136.86,
146.41, 166.45, 169.10; GC–MS (EI): m/z = 304.1 [M - 15]?.
2-Chloro-6-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (2q)
1H NMR (400 MHz, CDCl3) (d, ppm): 1.35 (12H, s, CH3), 2.53 (3H, s, CH3), 7.41
(1H, s, ArH) 7.48 (1H, s, ArH); 13C NMR (400 MHz, CDCl3) (d, ppm): 23.96,
24.85, 84.78, 126.18, 126.73, 150.54, 158.90; GC–MS (EI): m/z = 238.1 [M -
15]?.
2-Chloro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-6-
(trifluoromethyl)pyridine (2r)
1H NMR (400 MHz, CDCl3) (d, ppm): 1.36 (12H, s, CH3), 7.87 (1H, s, ArH) 7.93
(1H, s, ArH); 13C NMR (400 MHz, CDCl3) (d, ppm): 24.84, 85.40, 119.48, 122.21,
123.68, 132.82, 148.04, 151.81; GC–MS (EI): m/z = 292.1 [M - 15]?.
2-Chloro-6-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) pyridine
(2s)
1H NMR (400 MHz, CDCl3) (d, ppm): 1.35 (12H, s, CH3), 3.93 (3H, s, OCH3), 7.01
(1H, s, ArH) 7.22 (1H, s, ArH); 13C NMR (400 MHz, CDCl3) (d, ppm): 24.84,
54.06, 84.73, 114.58, 120.82, 148.19, 163.74; GC–MS (EI): m/z = 269.1 [M]?.
Acknowledgments The authors acknowledge the generous support of this study by Sundia MediTech
Company Ltd.
123

1926
L. Zeqing et al.
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