Carbon-boron bond cross-coupling reaction catalyzed by -PPh2 containing palladium-indolylphosphine complexes

Article abstract of DOI:10.1021/jo202472k

This study describes the application of indolylphosphine ligands with a diphenylphosphino moiety to the palladium-catalyzed borylation of aryl chlorides. The combination of palladium metal precursor with PPh ₂-Andole-phos, which comprises an inexpensive -PPh₂ group, provides highly effective catalysts for the borylation of aryl chlorides. A range of functional groups such as -CN, -NO₂, -CHO, -COMe, -COOMe, and -CF₃ was compatible, and the catalyst loading down to 0.025 mol % of Pd can be achieved. The Pd/PPh₂-Andole-phos system is able to catalyze both borylation reaction and Suzuki-Miyaura coupling reaction in a one-pot sequential manner for the direct synthesis of biaryl compounds in excellent yields.

Full text of DOI:10.1021/jo202472k

Note
pubs.acs.org/joc
Carbon−Boron Bond Cross-Coupling Reaction Catalyzed by −PPh2
Containing Palladium−Indolylphosphine Complexes
Wing Kin Chow, On Ying Yuen, Chau Ming So, Wing Tak Wong, and Fuk Yee Kwong*
State Key Laboratory of Chirosciences and Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic
University, Kowloon, Hong Kong
S
* Supporting Information
ABSTRACT: This study describes the application of
indolylphosphine ligands with a diphenylphosphino moiety
to the palladium-catalyzed borylation of aryl chlorides. The
combination of palladium metal precursor with PPh2-Andole-
phos, which comprises an inexpensive −PPh2 group, provides
highly effective catalysts for the borylation of aryl chlorides.
A range of functional groups such as −CN, −NO2, −CHO,
−COMe, −COOMe, and −CF3 was compatible, and the
catalyst loading down to 0.025 mol % of Pd can be achieved.
The Pd/PPh2-Andole-phos system is able to catalyze both
borylation reaction and Suzuki−Miyaura coupling reaction in a
one-pot sequential manner for the direct synthesis of biaryl compounds in excellent yields.
rylboronic acids, boronate esters, and potassium trifluoro-
borate salts are used as important chemical building
the Pd/XPhos system.4d The application of dialkylphosphino-
substituted ligands is believed to be the key to generate the
highly active Pd catalyst in these borylations. However, the cost
of the dialkylphosphino moiety is more readily available than
the diphenylphosphino analogue from commercial sources.9
Therefore, diphenyl-substituted phosphino ligands would be
attractive if they can reach certain catalytic activity with respect
to dialkylphosphino-derived ligands.10 Herein, we report our
findings of effective ligands bearing a −PPh2 moiety only, for
the Pd-catalyzed borylation of aryl chlorides at 0.05−2 mol %
Pd loading.
We initially tested the feasibility of aryl chloride borylation
using nonactivated 4-chlorotoluene and B2pin2 as the model
substrates (Table 1). It is well-known that highly electron-rich
phosphines (e.g., phosphine containing −PCy2 or −P-t-Bu2
groups) can handle a range of aryl chloride/tosylate couplings.
On the contrary, we are interested in investigating the
inexpensive Ar−PPh2 scaffold that deals with an aromatic
bond-forming reaction from aryl chlorides. Thus, replacing the
−PCy2 group with the −PPh2 moiety in our previously reported
indolyl ligands gave a series of Ar−PPh2 phosphines L1−L4.11
In our initial trials, ligand L3 (PPh2-Andole-phos) was found to
be the best ligand of choice in this reaction (Table 1, entry 3).
Commonly used inorganic bases were also screened. CsOAc
and KOAc were found to be superior to other bases (Table 2,
entries 1−7). Stronger bases such as K2CO3, K3PO4, and CsF
(Table 2, entries 3, 4, and 6) undesirably promoted further
coupling reactions to generate symmetrical biaryl compounds.
This implies an opportunity to undergo sequential Suzuki
A
blocks and intermediates in organic synthesis. They have
versatile applications in metal-catalyzed cross-coupling reac-
tions. Notably, Suzuki−Miyaura cross-coupling reaction is one
of the most successful methodologies to utilize the organo-
boron for carbon−carbon bond formation.1 Arylboronic acids/
boronate esters are highly stable and nontoxic, which are
desirable properties for coupling reactions. The conventional
route for preparing arylboronic acids and esters goes through
the metal−halogen exchange (e.g., Mg or Li) from aryl
bromides/iodides and subsequent trapping with trialkylborates.
However, this synthetic pathway is incompatible with base-
sensitive functional groups (e.g., aldehyde, ketone, nitrile, etc.).1
Therefore, additional protection and deprotection steps are re-
quired in these routes. Moreover, the aforementioned synthetic
protocol is incompatible with relatively inexpensive and broadly
available aryl chlorides. To expand the scope of organoboron
reagents, transition-metal-catalyzed borylation of aryl halides
with alkoxyboranes has emerged. Re, Ru, Rh, and especially Ir
catalysts were found to be applicable for the direct C−H
borylation of arenes.2 Miyaura pioneered a Pd-catalyzed
borylation of aryl halides in 1995.3 Recently, a number of
palladium-catalyzed processes have emerged for the conversion
of aryl iodides/bromides to the corresponding boronate
esters.4,5 Nickel-catalyzed protocols have also been reported
by Percec and co-workers.6 In fact, there are limited palladium
catalyst systems that are effective for the borylation of
unactivated aryl chlorides, which are generally more desirable
as they are relatively low cost and with broad availability.4c,d,j,p,7
Recently, Buchwald and co-workers reported an active catalyst
for the borylation of aryl chlorides.8 Molander also reported the
direct synthesis of arylboronic acids from aryl chlorides using
Received: December 1, 2011
Published: March 13, 2012
© 2012 American Chemical Society
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Note
a
The scope of the borylation reaction was then investigated
under the optimized conditions. A range of nonactivated aryl
chlorides were examined, and the results are listed in Table 3.
Table 1. Screening of Ligands
Table 3. Palladium-Catalyzed Borylation of Nonactivated
a
Aryl Chlorides
b
entry
ligand
Pd/ligand
yield %
1
2
3
4
5
6
L1
L2
L3
L4
L3
L3
1:2
1:2
1:2
1:2
1:4
1:8
20
26
43
33
73
64
a
Reaction conditions: ArCl (0.5 mmol), B2pin2 (0.75 mmol), KOAc
(1.5 mmol), and dioxane (1.5 mL) were stirred for 24 h at 110 °C
b
under nitrogen. Calibrated GC yields were reported using dodecane
as internal standard.
a
Table 2. Initial Optimization of Reaction Parameters
b
entry
base
solvent
yield %
1
2
3
4
5
6
7
8
9
10
KOAc
CsOAc
K3PO4
K2CO3
KOPiv
CsF
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
THF
73
88
70
81
70
52
31
64
18
27
43
36
69
88
a
Reaction conditions: ArCl (0.5 mmol), B2pin2 (0.55 mmol), CsOAc
(1.5 mmol), Pd/ligand = 1:4, and solvent (1.5 mL) were stirred for
24 h at 110 °C under nitrogen; mol % of Pd (from Pd2dba3) with respect
to ArCl. Isolated yields.
b
KF
KOAc
KOAc
KOAc
KOAc
KOAc
CsOAc
CsOAc
The nonactivated aryl chlorides containing ortho-methyl-
substituted groups were found to be compatible coupling
partners (Table 3, entries 2 and 4). The highly sterically hindered
aryl chlorides could also be coupled to furnish product in
moderate yield (Table 3, entry 5).12
toluene
t-BuOH
dioxane
dioxane
dioxane
dioxane
c
11
d
12
e
13
f
Apart from nonactivated aryl chlorides, activated aryl
chlorides were also applicable substrates in the Pd/PPh2-
Andole-phos catalytic system (Table 4). KOAc was found to be
a better base than CsOAc for the borylation of activated aryl
chlorides. Common functional groups such as −CN, −NO2,
−CHO, −COMe, −COOMe, and −CF3 were compatible
under these mild reaction conditions (Table 4, entries 1−9).
Excellent yields were generally obtained using 0.05 to 1 mol %
of Pd. 4-Chlorobenzaldehyde showed a better yield when a
higher catalyst loading and shorter reaction time were used
(Table 4, entry 9). It is noteworthy that the scope of borylation
of chloride can also be extended to vinyl chloride (Table 4,
entry 11). Excellent product yield from 1-chlorocyclopent-1-ene was
obtained. Heteroaryl chloride was also examined. 2-Chlorothio-
phene provided moderate product yield (Table 4, entry 12).
In light of further application of borylation for subsequent
biaryl synthesis, we are attracted to examine a one-pot procedure
for generating unsymmetrical biaryls starting from both electro-
philic partners. The one-pot two-step unsymmetrical biaryl
synthesis could be successfully achieved by adding the second
14
a
Reaction conditions: ArCl (0.5 mmol), B2pin2 (0.75 mmol), base
(1.5 mmol), Pd/ligand = 1:4, and solvent (1.5 mL) were stirred for 24 h
at 110 °C under nitrogen. Calibrated GC yields were reported using
dodecane as internal standard. The reaction was conducted at 90 °C.
The reaction was conducted at 130 °C. B2neop2 acts as the boron
source. B2pin2 (0.55 mmol) was used.
b
c
d
e
f
reaction to synthesize unsymmetrical biaryl compounds after
modifying the reaction conditions. Among organic solvents
surveyed, dioxane provided the best product yield when
compared with THF, t-butyl alcohol, and toluene (Table 2,
entries 1 and 8−10). In general, the reaction proceeds faster if the
reaction temperature is higher. In our reaction temperature study,
either increasing or decreasing the reaction temperature would
decrease the desired product yield. A temperature of 110 °C gave
the best yield (Table 2, entries 1, 11, and 12) and was thus chosen
as the reaction temperature for further study. The use of 1.1 equiv
of B2pin2 provided the same yield as 1.5 equiv (Table 2, entry 14).
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Note
Table 4. Palladium-Catalyzed Borylation of Activated Aryl,
Heteroaryl, and Vinyl Chlorides
Table 5. Palladium-Catalyzed One-Pot Two-Step
Preparation of Unsymmetrical Biaryl Compounds
a
a
a
Reaction conditions: 1st aryl chlorides (0.5 mmol), 2nd aryl or
heteroaryl chlorides (0.5 mmol), B2pin2 (0.505 mmol), KOAc(1.5 mmol),
b
K3PO4 (1.5 mmol), dioxane (2.0 mL), Pd/ligand =1:4. Isolated yields.
c
Second step was stirred for 2 h.
In summary, we have achieved the first general borylation
of aryl chlorides using a ligand with only a −PPh2 moiety. The
indolyl phosphine ligands with a significantly cheaper
diphenylphosphino moiety are able to handle the borylation
of aryl chlorides which could only deal with dialkylphosphino-
substituted phosphine ligands in the previous reports. With the
Pd/PPh2-Andole-phos catalyst system, a range of aryl chlorides
bearing base-sensitive functional groups (−CN, −NO2, −CHO,
−COMe, −COOMe) can be converted to their borylated
products. The catalyst loading ranges from 0.05 to 2 mol % of
Pd in general. A direct synthesis of unsymmetrical biaryls from
aryl chlorides using one-pot two-step procedures can also be
successfully accomplished using this catalyst system.
a
Reaction conditions: ArCl (1.0 mmol), B2pin2 (1.1 mmol), CsOAc
(3.0 mmol), Pd/ligand = 1:4, and solvent (3.0 mL) were stirred for
24 h at 110 °C under nitrogen; mol % of Pd (from Pd2dba3) with
respect to ArCl. Isolated yields. The reaction was stirred for 2 h.
b
c
aryl chlorides and K3PO4 base after the borylation reaction
without isolation of the borylated intermediates (Table 5). In
particular, no additional catalyst was added before conducting the
second Suzuki step in the reaction sequence. A wide range of
substrate scope can be tolerated by using this catalytic system
(Table 5), including heteroaryl and sterically hindered aryl
chlorides (Table 5, entries 4−8).
EXPERIMENTAL SECTION
■
General Information. Unless otherwise noted, all reagents were
purchased from commercial suppliers and used without purification.
All borylation reactions were performed in resealable screw cap
Schlenk flasks (approximately 20 mL volume) in the presence of a
Teflon-coated magnetic stir bar (4 mm × 10 mm). Dioxane, toluene,
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Note
and tetrahydrofuran (THF) were distilled from sodium and sodium
benzophenone ketyl under nitrogen. All indolyl ligands were prepared
according to the reported procedures.11 Commercially available aryl
chlorides (liquid form only) were purified by passing through a short
plug (0.5 cm width × 4 cm height) of neutral alumina or distillation.
Thin layer chromatography was performed on precoated silica gel
60 F254 plates. Silica gel (70−230 and 230−400 mesh) was used
under reduced pressure. The crude products were purified by flash
column chromatography on silica gel (230−400 mesh) to afford the
desired product.
4,4,5,5-Tetramethyl-2-p-tolyl-1,3,2-dioxaborolane (Table 3,
entry 1).4e Eluents (EtOAc/hexane = 1:40, Rf = 0.38) was used for
1
flash column chromatography: H NMR (400 MHz, CDCl3) δ 1.40
(s, 12H), 2.42 (s, 3H), 7.25 (d, J = 8.0 Hz, 2H), 7.78 (d, J = 7.6 Hz,
2H); 13C NMR (100 MHz, CDCl3) δ 21.7, 24.8, 83.5, 128.5, 134.8,
141.3; MS (EI) m/z (relative intensity) 218.1 (M+, 31), 203.1 (43),
132.1 (60), 119.1 (100), 91.1 (14).
1
for column chromatography. H NMR spectra were recorded on a
400 MHz spectrometer. Spectra were referenced internally to the
residual proton resonance in CDCl3 (δ 7.26 ppm) or with
tetramethylsilane (TMS, δ 0.00 ppm) as the internal standard.
Chemical shifts (δ) were reported as part per million (ppm) in δ scale
downfield from TMS. 13C NMR spectra were referenced to CDCl3
(δ 77.0 ppm, the middle peak). Coupling constants (J) were reported
in hertz (Hz). High-resolution mass spectra (HRMS) were obtained
on a FT-ICR mass spectrometer (ESIMS).
General Procedure for Screening: Pd2(dba)2 (0.0046 g, 0.005
mmol) and ligand (Pd/L = 1:4) were loaded into a Schlenk tube
equipped with a Teflon-coated magnetic stir bar. The tube was
evacuated and flushed with nitrogen for three cycles. Precomplexation
was applied by adding freshly distilled solvent (0.5 mL) into the
tube. The palladium complex stock solution was stirred for 10 min.
4-Chlorotoluene (0.5 mmol), boron source (0.75 mmol), and base
(1.5 mmol) were loaded into the tube. The solvent (1 mL) was added
with continuous stirring at room temperature. The tube was then
placed into a preheated oil bath with the temperature indicated in
the table and stirred for 24 h. After the completion of the reaction, the
reaction tube was allowed to cool at room temperature. Ethyl acetate
(∼10 mL), dodecane (113 μL, internal standard), and water were
added. The organic layer was subjected to GC analysis. The GC yield
obtained was previously calibrated by authentic sample/dodecane
calibration curve.
General Procedure for Borylation of Aryl Chlorides: Pd2(dba)3
(0.0046 g, 0.005 mmol) and ligand (Pd/L = 1:4) were loaded into
a Schlenk tube equipped with a Teflon-coated magnetic stir bar.
The tube was evacuated and flushed with nitrogen three times.
Precomplexation was applied by adding freshly distilled dioxane
(0.5 mL) into the tube. The solution was stirred for 10 min. Aryl
chloride (0.5 mmol), B2pin2 (0.55 mmol), and KOAc (1.5 mmol)
were loaded into the tube. Dioxane (1.0 mL) was then added with
continuous stirring at room temperature. The tube was placed into a
preheated oil bath (110 °C) for the time period as indicated in the
table. After the completion of the reaction, the reaction tube was
allowed to cool at room temperature. Ethyl acetate (∼10 mL) and
water were added. The organic layer was subjected to GC analysis.
The aqueous layer was washed with ethyl acetate. The filtrate was
concentrated under reduced pressure. The crude product was purified
by flash column chromatography on silica gel (230−400 mesh) to
afford the desired product.
General Procedure for One-Pot Two-Step Coupling of Aryl
Chloride: Pd2(dba)3 (0.0046 g, 0.005 mmol) and ligand (Pd/L = 1:4)
were loaded into a Schlenk tube equipped with a Teflon-coated
magnetic stir bar. The tube was evacuated and flushed with nitrogen
three times. Precomplexation was applied by adding freshly distilled
dioxane (0.5 mL) into the tube. The solution was stirred for 10 min.
The first aryl chloride (0.5 mmol), B2pin2 (0.505 mmol), and KOAc
(1.5 mmol) were loaded into the tube. Dioxane (1 mL) was then
added with continuous stirring at room temperature. The tube was
then placed into a preheated oil bath (110 °C) for the time period as
indicated in the table. After the completion of the reaction, the
reaction tube was allowed to cool at room temperature. K3PO4 and the
second aryl or heteroaryl chlorides were loaded into the tube under
nitrogen. Dioxane (0.5 mL) was added with continuous stirring at
room temperature. The tube was then placed into a preheated oil bath
(110 °C) for the time period as indicated in the table. After the
completion of the reaction, the reaction tube was allowed to cool at
room temperature. Ethyl acetate (∼10 mL) and water were added.
The organic layer was subjected to GC analysis. After analyzing GC
spectra, the crude product in the organic layer was extracted. The
aqueous layer was washed with EtOAc. The filtrate was concentrated
4,4,5,5-Tetramethyl-2-o-tolyl-1,3,2-dioxaborolane (Table 3,
entry 2).4e Eluents (EtOAc/hexane = 1:40, Rf = 0.35) was used for
1
flash column chromatography: H NMR (400 MHz, CDCl3) δ 1.41
(s, 12H), 2.61 (s, 3H), 7.21−7.24 (m, 2H), 7.38 (t, J = 7.6 Hz, 1H),
7.84 (d, J = 7.2 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 22.2, 24.9,
83.3, 124.7, 129.7, 130.8, 135.8, 144.8; MS (EI) m/z (relative intensity)
218.1 (M+, 23), 203.1 (36), 161.1 (83), 119.1 (100), 91.1 (21).
4,4,5,5-Tetramethyl-2-m-tolyl-1,3,2-dioxaborolane (Table 3,
entry 3).13 Eluents (EtOAc/hexane = 1:40, Rf = 0.35) was used for
1
flash column chromatography: H NMR (400 MHz, CDCl3) δ 1.40
(s, 12H), 2.41 (s, 3H), 7.33 (d, J = 4.8 Hz, 2H), 7.67−7.71 (m, 2H);
13C NMR (100 MHz, CDCl3) δ 21.2, 24.8, 83.6, 127.6, 131.7, 132.0,
135.3 137.0; MS (EI) m/z (relative intensity) 218.1 (M+, 36), 203.1
(43), 132.1 (77), 119.1 (100), 91.1 (17).
4,4,5,5-Tetramethyl-2-(2,3-dimethylphenyl)-1,3,2-dioxaboro-
lane (Table 3, entry 4).14 Eluents (EtOAc/hexane = 1:40, Rf = 0.38)
was used for flash column chromatography: 1H NMR (400 MHz,
CDCl3) δ 1.42 (s, 12H), 2.34 (s, 3H), 2.55 (s, 3H), 7.15 (t, J = 7.4 Hz,
1H), 7.28 (d, J = 6.8 Hz, 1H), 7.69 (d, J = 7.2 Hz, 1H); 13C NMR
(100 MHz, CDCl3) δ 18.4, 20.4, 24.8, 83.4, 124.8, 132.3, 133.5, 136.4,
143.0; MS (EI) m/z (relative intensity) 232.1 (M+, 36), 217.1 (20),
175.1 (100), 132.1 (77).
4,4,5,5-Tetramethyl-2-(2,6-dimethylphenyl)-1,3,2-dioxaboro-
lane (Table 3, entry 5).4c Eluents (EtOAc/hexane = 1:40, Rf = 0.35)
was used for flash column chromatography: 1H NMR (400 MHz,
CDCl3) δ 1.44 (s, 12H), 2.47 (s, 6H), 7.00 (d, J = 7.6 Hz, 2H), 7.18
(t, J = 7.6 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 22.2, 24.9, 83.6,
126.4, 129.1, 141.7; MS (EI) m/z (relative intensity) 232.1 (M+, 31),
217.1 (7), 175.1 (100), 132.1 (64), 105.1 (13).
4,4,5,5-Tetramethyl-2-(naphthalen-2-yl)-1,3,2-dioxaboro-
lane (Table 3, entry 6).15 Eluents (EtOAc/hexane = 1:40, Rf = 0.33)
was used for flash column chromatography: 1H NMR (400 MHz,
CDCl3) δ 1.47 (s, 12H), 7.55−7.59 (m, 2H), 7.90−7.94 (m, 2H), 7.99
(d, J = 8.4 Hz, 2H), 8.53 (s, 1H); 13C NMR (100 MHz, CDCl3) δ
24.8, 83.8, 125.7, 126.9, 127.6, 128.5, 130.4, 132.8, 135.0, 136.2; MS
(EI) m/z (relative intensity) 254.1 (M+, 46), 239.1 (11), 168.1 (64),
154.1 (100).
4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)benzonitrile
(Table 4, entry 1).16 Eluents (EtOAc/hexane = 1:30, Rf = 0.24) was
1
used for flash column chromatography: H NMR (400 MHz, CDCl3)
δ 1.33 (s, 12H), 7.61 (d, J = 8.4 Hz, 2H), 7.87 (d, J = 8.0 Hz, 2H); 13C
NMR (100 MHz, CDCl3) δ 24.7, 84.3, 114.4, 118.6, 130.9, 134.9; MS
(EI) m/z (relative intensity) 229.1 (M+, 10), 214.1 (100), 143.1 (71),
130.1 (46), 103.0 (6).
4,4,5,5-Tetramethyl-2-(4-nitrophenyl)-1,3,2-dioxaborolane
(Table 4, entry 2).17 Eluents (EtOAc/hexane = 1:30, Rf = 0.24) was
1
used for flash column chromatography: H NMR (400 MHz, CDCl3)
δ 1.36 (s, 12H), 7.95 (d, J = 8.4 Hz, 2H), 8.17 (d, J = 6.8 Hz, 2H);
13C NMR (100 MHz, CDCl3) δ 24.8, 84.5, 122.3, 135.6, 149.7; MS
(EI) m/z (relative intensity) 249.1 (M+, 4), 234.1 (100), 163.1 (61),
150.0 (29).
3-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)benzonitrile
(Table 4, entry 3).18 Eluents (EtOAc/hexane = 1:30, Rf = 0.21) was
used for flash column chromatography: 1H NMR (400 MHz, CDCl3) δ
1.34 (s, 12H), 7.46 (t, J = 9.5 Hz, 1H), 7.71 (d, J = 7.6 Hz, 1H), 8.00
(d, J = 7.6 Hz, 1H), 8.08 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 24.7,
84.3, 111.9, 118.6, 128.3, 134.2, 138.2, 138.6; MS (EI) m/z (relative
intensity) 229.1 (M+, 19), 214.1 (94), 143.1 (100), 130.1 (61).
1-(4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-
ethanone (Table 4, entry 4).19 Eluents (EtOAc/hexane = 1:30,
Rf = 0.12) was used for flash column chromatography: 1H NMR
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Note
(400 MHz, CDCl3) δ 1.34 (s, 12H), 2.59 (s, 3H), 7.90 (d, J = 12.8 Hz,
4H); 13C NMR (100 MHz, CDCl3) δ 24.7, 26.6, 84.1, 127.1, 134.8,
138.9, 198.2; MS (EI) m/z (relative intensity) 246.1 (M+, 14), 231.1
(100), 203.1 (7), 160.1 (36), 147.0 (99), 131.0 (26).
124.3, 128.0, 128.1, 132.9, 143.1, 145.4, 147.9; MS (EI) m/z (relative
intensity) 224.0 (M+, 100), 194.0 (36), 177.0 (50), 151.0 (57), 140.0 (14).
4-(4-Acetophenyl)benzonitrile (Table 5, entry 2).23 Eluents
(EtOAc/hexane = 1:9, Rf = 0.15) was used for flash column chromato-
graphy: 1H NMR (400 MHz, CDCl3) δ 2.61 (s, 3H), 7.65−7.71 (m, 6H),
8.04 (d, J = 6.8 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 26.5, 111.5,
118.4, 127.2, 127.7, 128.9, 132.5, 136.6, 143.2, 143.9, 197.2; MS (EI)
m/z (relative intensity) 221.1 (M+, 33), 206.1 (100), 178.0 (23), 151.0
(24), 103.1 (3).
(4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-
(phenyl)methanone (Table 4, entry 5).18 Eluents (EtOAc/hexane =
1
1:30, Rf = 0.30) was used for flash column chromatography: H NMR
(400 MHz, CDCl3) δ 1.38 (s, 12H), 7.48 (t, J = 7.6 Hz, 2H), 7.58 (t, J =
7.4 Hz, 1H), 7.80 (t, J = 8.6 Hz, 4H), 7.95 (d, J = 8 Hz, 2H); 13C NMR
(100 MHz, CDCl3) δ 24.8, 84.1, 128.2, 128.9, 130.0, 132.4, 134.5, 137.4,
139.7, 196.7; MS (EI) m/z (relative intensity) 308.1 (M+, 68), 293.1 (70),
231.1 (25), 209.1 (100), 105.1 (77), 77.1 (38).
2-(4-(Trifluoromethyl)phenyl)-4,4,5,5-tetramethyl-1,3,2-di-
oxaborolane (Table 4, entry 6).4e Eluents (EtOAc/hexane = 1:30,
Rf = 0.35) was used for flash column chromatography: 1H NMR
(400 MHz, CDCl3) δ 1.38 (s, 12H), 7.65 (d, J = 7.6 Hz, 2H), 7.96
(d, J = 7.6 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 24.8, 84.2, 122.8,
124.2, 125.5, 128.2, 132.8; 19F NMR (400 MHz, CDCl3) δ −63.0; MS
(EI) m/z (relative intensity) 272.1 (M+, 9), 257.1 (100), 186.1 (79),
173.1 (80), 153.0 (7).
4-(4-Nitrophenyl)toluene (Table 5, entry 3).24 Eluents (EtOAc/
hexane = 1:20, Rf = 0.53) was used for flash column chromato-
1
graphy: H NMR (400 MHz, CDCl3) δ 2.46 (s, 3H), 7.33 (d, J =
7.6 Hz, 2H), 7.55 (d, J = 8.0 Hz, 2H), 7.73 (d, J = 7.0 Hz, 2H), 8.29
(d, J = 7.2 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 21.1, 124.0,
127.1, 127.4, 129.8, 135.7, 139.0, 146.8, 147.5; MS (EI) m/z (relative
intensity) 213.0 (M+, 100), 183.0 (26), 165.0 (49), 152.0 (69), 139.0 (10).
2-Acetophenyl-1,3-dimethylbenzene (Table 5, entry 4).25
Eluents (EtOAc/hexane = 1:50, Rf = 0.31) was used for flash column
1
chromatography: H NMR (400 MHz, CDCl3) δ 2.07 (s, 6H), 2.70
(s,3H), 7.17 (d, J = 6.0 Hz, 2H), 7.23 (t, J = 6.0 Hz, 1H), 7.31 (d, J =
6.8 Hz, 2H), 8.09 (d, J = 6.8 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ
20.6, 26.4, 127.3, 127.4, 128.5, 129.3, 135.4, 135.6, 140.6, 146.3, 197.6;
MS (EI) m/z (relative intensity) 224.1 (M+, 44), 209.1 (100), 178.1
(6), 165.1 (39), 115.1 (3), 106.0 (1).
Methyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-
benzoate (Table 4, entry 7).18 Eluents (EtOAc/hexane = 1:30,
1
Rf = 0.24) was used for flash column chromatography: H NMR (400
MHz, CDCl3) δ 1.35 (s, 12H), 3.91 (s, 3H), 7.45 (t, J = 7.6 Hz, 1H),
7.99 (d, J = 7.2 Hz, 1H), 8.13 (d, J = 8.0 Hz, 1H), 8.48 (s, 1H); 13C
NMR (100 MHz, CDCl3) δ 24.8, 51.9, 84.0, 127.7, 129.4, 132.2, 135.7,
139.1, 167.0; MS (EI) m/z (relative intensity) 262.1 (M+, 10), 247.1
(27), 231.1 (14), 219.1 (100), 163.1 (79), 131.0 (29), 103.1 (29).
3-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-
benzaldehyde (Table 4, entry 8).20 Eluents (EtOAc/hexane =
1:30, Rf = 0.21) was used for flash column chromatography: 1H NMR
(400 MHz, CDCl3) δ 1.33 (s, 12H), 7.49 (t, J = 7.4 Hz, 1H), 7.94
(d, J = 7.6 Hz, 1H), 8.03 (d, J = 7.2 Hz, 1H), 8.28 (s, 1H), 10.1 (s, 1H);
13C NMR (100 MHz, CDCl3) δ 24.7, 84.0, 128.2, 131.1, 135.6, 136.9,
3-Methyl-2-(4-nitrophenyl)thiophene (Table 5, entry 5).
Eluents (EtOAc/hexane = 1:15, Rf = 0.35) was used for flash column
1
chromatography: yellow liquid; H NMR (400 MHz, CDCl3) δ 2.41
(s, 3H), 7.02 (d, J = 8.4 Hz, 1H), 7.36 (d, J = 5.2 Hz, 1H), 7.64 (d, J =
7.0 Hz, 2H), 8.28 (d, J = 7.0 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ
15.3, 123.8, 125.5, 129.1, 131.8, 135.3, 135.4, 141.5, 146.4; MS (EI)
m/z (relative intensity) 219.0 (M+, 100), 203.0 (1), 189.0 (28), 171.0
(36), 128.1 (27); HRMS (ESI) calcd for C11H9NO2S [M + H+]
220.0432, found 220.0441.
140.4, 192.2; MS (EI) m/z (relative intensity) 232.1 (M+, 29), 217.1
(46), 189.1 (50), 172.1 (14), 146.1 (27), 133.1 (100).
2-(4-Nitrophenyl)quinoline (Table 5, entry 6). Eluents (EtOAc/
hexane = 1:4, Rf = 0.41) was used for flash column chromatography:
4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-
benzaldehyde (Table 4, entry 9).18 Eluents (EtOAc/hexane =
1:30, Rf = 0.24) was used for flash column chromatography: 1H NMR
(400 MHz, CDCl3) δ 1.34 (s, 12H), 7.84 (d, J = 8.4 Hz, 2H), 7.95 (d,
J = 8.0 Hz, 2H), 10.02 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 24.7,
84.2, 128.5, 135.1, 138.0, 192.3; MS (EI) m/z (relative intensity) 232.1
(M+, 19), 217.1 (96), 203.1 (1), 146,1 (89), 133.1 (100).
1
yellow solid; mp 123.5−127.9 °C; H NMR (400 MHz, CDCl3) δ
7.59 (t, J = 7.2 Hz, 1H), 7.78 (t, J = 7.2 Hz, 1H), 7.87 (t, J = 9.6 Hz,
2H), 8.19 (d, J = 8.4 Hz, 1H), 8.27 (d, J = 8.4 Hz, 1H), 8.33 (s, 4H);
13C NMR (100 MHz, CDCl3) δ 118.6, 123.9, 127.2, 127.5, 128.1,
129.8, 130.1, 137.2, 145.3, 148.2, 154.3; MS (EI) m/z (relative
intensity) 250 (M+, 100), 220 (7), 204 (99), 128 (10); HRMS (ESI)
calcd for C15H10N2O2 [M + H+] 251.0821, found 251.0811.
3-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl 4-
methylbenzenesulfonate (Table 4, entry 10). Eluents (EtOAc/
hexane = 1:20, Rf = 0.25) was used for flash column chromatography:
3-(5-Acetylthiophen-2-yl)benzonitrile (Table 5, entry 7).
[CAS Registry Number; 893741-59-8] Eluents (EtOAc/hexane =
1
colorless liquid; H NMR (400 MHz, CDCl3) δ 1.32 (s, 12H), 2.44
1
1:4, Rf = 0.16) was used for flash column chromatography: H NMR
(s, 3H), 7.02−7.05 (m, 1H), 7.26−7.32 (m, 3H), 7.44 (s, 1H), 7.68
(d, J = 7.2 Hz, 1H), 7.71 (d, J = 8.4 Hz, 2H); 13C NMR (100 MHz,
CDCl3) δ 21.6, 24.7, 84.0, 124.9, 128.3, 128.4, 129.0, 129.6, 132.3,
133.2, 145.2, 149.2; MS (EI) m/z (relative intensity) 374.1 (M+, 39),
359.1 (16), 177.1 (24), 155.0 (77), 91.1 (100); HRMS (ESI) calcd for
C19H23O5SB [M + Na+] 397.1257, found 397.1266.
(400 MHz, CDCl3) δ 2.58 (s, 3H), 7.37 (d, J = 4.0 Hz, 1H), 7.53 (t,
J = 8.0 Hz, 1H), 7.63 (d, J = 7.6 Hz, 1H), 7.69 (d, J = 4.0 Hz, 1H),
7.83−7.89 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 26.5, 113.3,
118.0, 125.1, 129.3, 130.2, 131.9, 133.3, 134.4, 144.4, 149.1, 190.3; MS
(EI) m/z (relative intensity) 227.0 (M+, 40), 212.0 (100), 140.0 (44),
113.0 (6).
2-Cyclopentenyl-4,4,5,5-tetramethyl-1,3,2-dioxaborolane
(Table 4, entry 11).8a Eluents (EtOAc/hexane = 1:40, Rf = 0.16) was
3-(Acridin-9-yl)benzonitrile (Table 5, entry 8). Eluents (EtOAc/
hexane = 1:1, Rf = 0.55) was used for flash column chromatography:
1
used for flash column chromatography: H NMR (400 MHz, CDCl3)
1
yellow liquid; H NMR (400 MHz, CDCl3) δ 7.48−7.52 (m, 2H),
δ 1.29 (s, 12H), 1.80−1.89 (m, 2H), 2.39−2.47 (m, 4H), 6.56 (t, J =
2.0 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 23.9, 24.7, 34.4, 34.7,
83.0, 147.5; MS (EI) m/z (relative intensity) 194.1 (M+, 23), 179.1
(31), 165.1 (29), 108.1 (100), 67.1 (46).
7.57−7.59 (m, 2H), 7.72−7.85 (m, 5H), 7.91−7.94 (m, 1H), 8.33 (d,
J = 8.8 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 113.1, 118.3, 124.7,
125.8, 126.4, 129.5, 129.9, 130.2, 132.1, 133.8, 134.9, 137.5, 143.8,
148.7; MS (EI) m/z (relative intensity) 280.1 (M+, 100), 251.0 (10),
207.0 (6), 177.0 (1), 126.0 (14); HRMS (ESI) calcd for C20H12N2
[M + H+] 281.1079, found 281.1070.
4,4,5,5-Tetramethyl-2-(thiophen-2-yl)-1,3,2-dioxaborolane
(Table 4, entry 12).21 Eluents (EtOAc/hexane = 1:40, Rf = 0.23) was
1
used for flash column chromatography: H NMR (400 MHz, CDCl3)
δ 1.38 (s, 12H), 7.22−7.24(m, 1H), 7.66−7.70 (m, 2H); 13C NMR
(100 MHz, CDCl3) δ 24.7, 84.0, 128.2, 132.3, 137.1; MS (EI) m/z
(relative intensity) 210 (M+, 43), 195.0 (41), 124 (72), 111.0 (100),
85 (24).
ASSOCIATED CONTENT
■
S
* Supporting Information
4-(4-Nitrophenyl)benzonitrile (Table 5, entry 1).22 Eluents
(EtOAc/hexane = 1:4, Rf = 0.34) was used for flash column chromato-
1
Copies of H NMR, 13C NMR, and HRMS spectra. This
1
material is available free of charge via the Internet at http://
pubs.acs.org.
graphy: H NMR (400 MHz, CDCl3) δ 7.75−7.83 (m, 6H), 8.37
(d, J = 7.8 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 112.7, 118.3,
3547
dx.doi.org/10.1021/jo202472k | J. Org. Chem. 2012, 77, 3543−3548

The Journal of Organic Chemistry
Note
Walker, S. D.; Martinelli, J. R.; Buchwald, S. L. J. Am. Chem. Soc. 2005,
127, 468. (d) Iwasawa, T.; Komano, T.; Tajima, A.; Tokunaga, M.;
Obora, Y.; Fujihara, T.; Tsuji, Y. Organometallics 2006, 25, 4665.
(11) So, C. M.; Chow, W. K.; Choy, P. Y.; Lau, C. P.; Kwong, F. Y.
Chem.Eur. J. 2010, 16, 7996.
AUTHOR INFORMATION
Corresponding Author
*E-mail: bcfyk@inet.polyu.edu.hk.
Notes
■
(12) Reduction of ArCl to its corresponding Ar−H was observed in
∼28% GC yield (Table 3, entry 5); we thank a reviewer’s suggestion
on observing this side product.
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
(13) Qiu, D.; Mo, F.; Zheng, Z.; Zhang, Y.; Wang, J. Org. Lett. 2010,
12, 5474.
(14) Yan, G.; Jiang, Y.; Kuang, C.; Wang, S.; Liu, H.; Zhang, Y.;
Wang, J. Chem. Commun. 2010, 46, 3170.
(15) Praveen Ganesh, N.; Demory, E.; Gamon, C.; Blandin, V.;
Chavant, P. Y. Synlett 2010, 2403.
We thank the Research Grants Council of Hong Kong (GRF:
PolyU5014/10P), PolyU Development Grant (1BD07), and
State Key Laboratory of Chirosciences (4-BBX-3) for financial
support.
(16) Guillen, E.; Hierrezuelo, J.; Martinez-Mallorquin, R.; Lopez-
Romero, J. M.; Rico, R. Tetrahedron 2011, 67, 2555.
(17) Whittaker, A. M.; Rucker, R. P.; Lalic, G. Org. Lett. 2010, 12,
3216.
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3548
dx.doi.org/10.1021/jo202472k | J. Org. Chem. 2012, 77, 3543−3548