Practical synthesis of pinacolborane for one-pot synthesis of unsymmetrical biaryls via aromatic C-H borylation-cross-coupling sequence

Article abstract of DOI:10.1016/j.tet.2008.03.102

A method for practical preparation of pinacolborane from borane-diethylaniline and pinacol was newly developed. Aromatic C-H borylation of arenes with pinacolborane or bis(pinacolato)diboron catalyzed by 1/2[Ir(OMe)(COD)]₂-(4,4′-di-tert-butyl-2,2′-bipyridine) at 25 °C in hexane to give arylboronic esters was directly followed by cross-coupling with aromatic bromides at 60 °C in the presence of PdCl₂(dppf) (3.0 mol %) and K₃PO₄ in DMF. This one-pot, two-step procedure provided a variety of unsymmetrical biaryls in high yields.

Full text of DOI:10.1016/j.tet.2008.03.102

Tetrahedron 64 (2008) 4967–4971
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Tetrahedron
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Practical synthesis of pinacolborane for one-pot synthesis of unsymmetrical
biaryls via aromatic C–H borylation–cross-coupling sequence
*
Takao Kikuchi, Yusuke Nobuta, Junko Umeda, Yasunori Yamamoto ,
*
*
Tatsuo Ishiyama , Norio Miyaura
Division of Chemical Process Engineering, Graduate School of Engineering, Hokkaido University, Sapporo 060-8628, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
A method for practical preparation of pinacolborane from borane-diethylaniline and pinacol was newly
developed. Aromatic C–H borylation of arenes with pinacolborane or bis(pinacolato)diboron catalyzed by
1/2[Ir(OMe)(COD)]2-(4,40-di-tert-butyl-2,20-bipyridine) at 25 ꢀC in hexane to give arylboronic esters was
directly followed by cross-coupling with aromatic bromides at 60 ꢀC in the presence of PdCl2(dppf)
(3.0 mol %) and K3PO4 in DMF. This one-pot, two-step procedure provided a variety of unsymmetrical
biaryls in high yields.
Received 29 February 2008
Received in revised form 24 March 2008
Accepted 27 March 2008
Available online 3 April 2008
Keywords:
Pinacolborane
Biaryls
Ó 2008 Elsevier Ltd. All rights reserved.
Boron
C–H activation
Cross-coupling
1. Introduction
Pinacolborane necessary for these coupling reactions is available
from pinacol and borane–THF or borane–methyl sulfide complex
Unsymmetrical biaryls are an important class of compounds due
to the frequent occurrence of these fragments in natural products,
pharmaceuticals, agrochemicals, and functional organic materials.1
Transition metal-catalyzed cross-coupling of arylmetal compounds
with aryl halides or triflates has been proved to be a general
method applicable for preparation of such unsymmetrical biar-
yls.1d,f Among them, much attention has been focused on the use of
arylboronic acids or esters in laboratories and industries since they
are nontoxic, thermally stable, and inert to water and oxygen. A
traditional method for preparation of such arylboron compounds is
alkylation of B(OR)3 with aromatic lithium or magnesium re-
agents.2 Alternative and milder variants displayed high functional
group compatibility is palladium-catalyzed cross-couplings of
aryl halides and triflates with bis(pinacolato)diboron (B2pin2,
pin¼Me4C2O2)3 or pinacolborane (HBpin).4 Another economical
and environmentally benign process is transition metal-catalyzed
direct C–H borylation of arenes developed by Hartwig5 and Smith.6
Among the catalysts developed to date,7 a combination of [Ir(O-
Me)(COD)]2 and 4,40-di-tert-butyl-2,20-bipyridine (dtbpy) has been
recognized to be the best catalyst, which allowed stoichiometric
borylation of arenes with B2pin2 or HBpin at room temperature.8
(BMS).9 However, the protocol using BH3$THF and BH3$SMe2 is not
suitable for large-scale preparation due to inconveniences such as
the low concentration and instability of BH3$THF, and the high
volatility, flammability, and unpleasant odor of dimethyl sulfide
from BH3$SMe2. Because of the growing importance of pina-
colborane for the syntheses of boron compounds, a practical
method for its large-scale preparation is desirable. Here, we
describe a method for synthesizing pinacolborane from amine–
borane complexes and its use for a sequence of the iridium-cata-
lyzed aromatic C–H borylation and palladium-catalyzed
cross-coupling with aryl bromides to create a convenient one-pot
procedure for the synthesis of unsymmetrical biaryls.
2. Results and discussion
2.1. Synthesis of pinacolborane
The first synthesis of HBpin (1) in 63% yield reported by Knochel
involves reaction between BH3$SMe2 (BMS) and pinacol (Eq. 1).9
We used amine–borane complexes as a borane source due to their
advantage in large-scale preparation because of high thermal sta-
bility, low vapor pressure, and inflammability.10 Borane–amine
complexes are accessible by a reaction between metal borohydride
and HNR3Cl11 or by treatment of BH3$THF or BH3$SMe2 with
amines.10 To investigate their reaction with pinacol to give HBpin,
* Corresponding authors. Tel./fax: þ81 11 706 6561.
E-mail address: miyaura@eng.hokudai.ac.jp (N. Miyaura).
0040-4020/$ – see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.03.102

4968
T. Kikuchi et al. / Tetrahedron 64 (2008) 4967–4971
representative borane–amine complexes (2) were synthesized by
treatment of BH3$SMe with amines in THF.10 Evaporation of the
solvent and dimethyl sulfide in vacuo gave pure 2 in quantitative
yields for NH3, 2,6-diisopropylaniline, N,N-dimethylaniline, N,N-
diethylaniline, N-ethyl-N-isopropylaniline, and diisopropylaniline
(Eq. 2). Sodium borohydride is an economical borane source that
has been utilized for the preparation of BH3–THF or other borane-
base adducts by treatment with BF3$OEt2.12,13 Thus, we utilized this
protocol for preparation of BH3$N(Ph)Et2 (2d) (Eq. 3). The reaction
took place smoothly in the presence of N,N-diethylaniline in THF.
Filtration of NaBF4 through a Celite pad and evaporation of THF in
vacuo afford 2d in 89% yield. The preparation of 2d suffered from
some contamination of fluoroborane species. This byproduct was
completely eliminated when NaBH4 was used in slight excess
(1.07 equiv) of the required stoichiometry for BF3$OEt2. By this
method, 0.42 mol of pure 2d was obtained from 0.5 mol of NaBH4.
Further increase in steric hindrance by N-substituents resulted in
no reaction (entries 6 and 7). Selectivities giving HBpin toward 3
were parallel to these reaction rates. Thus, 100% selectivity was
achieved by diethylamine complex, which exhibited the fastest
reaction rate among the six complexes examined (entry 4). How-
ever, isolation of HBpin suffered from low yields (ca. 50%) because
of formation of nonvolatile 3 during distillation in vacuo. It was
difficult to prevent this equilibration when stoichiometric amounts
of 2d and pinacol were used,15 but the yield was improved to 75%
in the presence of 50% excess of BH3$N(Ph)Et2 toward pinacol
(entry 5).
2.2. One-pot synthesis of biaryls
Aromatic C–H borylation with HBpin (1) or B2pin2 takes place at
room temperature in the presence of an iridium(I)-dtbpy catalyst.
The preparation of 1.1 equiv of arylboronate (5) was directly fol-
lowed by cross-coupling with bromoarenes for one-pot synthesis of
biaryls (6) (Scheme 1).
O
O
pinacol
BH3·SMe2
H
B
ð1Þ
1 (HBpin)
O
O
1/2B2pin2 or HBpin
H
B
amine
1/2[Ir(OMe)(COD)]2-dtbpy
hexane, 25 °C
BH3·SMe2
BH3·amine
FG
4
FG
2a: BH3·NH3
5
2b: BH3·NH2C6H3-2,5-(i-Pr)2
2c: BH3·N(Ph)Me2
2d: BH3·N(Ph)Et2
ð2Þ
ð3Þ
Br
2e: BH3·N(Ph)(i-Pr)Et
2f: BH3·N(Ph)(i-Pr)2
FG'
PdCl2(dppf), K3PO4
DMF
FG'
FG
N
4 BF3·OEt2
6
4PhNEt2 + 3NaBH4
4BH3·N(Ph)Et2 + 3NaBF4
2d (89%)
THF
t
t
Bu
Bu
O
O
O
O
B
B
N
Reaction of pinacol with these borane–amines complexes in
tetraglyme yielded HBpin (1) and B2pin3 (3)14 with various molar
ratios (Table 1). The conversions of borane–amine complexes (2,
d ꢁ21 to ꢁ6 ppm) and ratios of 1 (d 28 ppm) and 3 (d 20–22 ppm)
were determined by 11B NMR. The reaction was very slow for stable,
small amine complexes such as NH3 and dimethylaniline com-
plexes (entries 1 and 3) and fast for sterically hindered 2,6-diiso-
propylaniline and diethylaniline complexes (entries 2 and 4).
B2pin2
dtbpy
Scheme 1. One-pot synthesis of biaryls via aromatic C–H borylation–cross-coupling
sequence.
Results of previous studies on aromatic C–H borylation of aro-
matic compounds reported by Smith’s group6 and by us7,8 are
summarized in Scheme 2. Functional group tolerance of the bor-
ylation is very high. The reaction selectively occurs at the C–H bond
for substrates possessing Cl, Br, I, CF3, OMe, CO2Me, and CN groups.
The reaction occurs only at aromatic C–H bonds even when the
substrate has weaker benzylic C–H bonds.16,17 The regiochemistry
of the borylation of arenes is primarily controlled by the steric ef-
fects of substituents. The reaction occurs at C–H bonds located meta
or para to a substituent in preference to those located ortho. Thus,
1,2-disubstituted arenes bearing identical substituents yield aryl-
boronates as single isomers. The borylation of 1,3-disubstituted
arenes proceeds at the common meta position; therefore,
Table 1
Synthesis of pinacolboranea
O
O
B
O
O
pinacol
(4)
2
O
+
H
B
O
B
O
O
1 (HBpin)
3
Entry
2 (Amine¼)
NH3 (2a)
2,6-(i-Pr)2C6H3NH2 (2b)
PhNMe2 (2c)
Conversion/%b
1/3
Isolated yield/%
O
O
1/2B2pin2 or HBpin
1
2
3
4
5
6
7
12
82
43
100
100
0
42:58
85:15
60:40
100:0
100:0
Ar-H
Ar
B
1/2[Ir(OMe)(COD)]2-dtbpy
hexane, 25 °C
PhNEt2 (2d)
(50)
(75)
PhNEt2 (2d)c
X
X
PhN(i-Pr)Et (2e)
PhN(i-Pr)2 (2f)
0
H
X
H
H
a
Z
A mixture of amine–borane complex (50 mmol) and pinacol (50 mmol) in tet-
raglyme (5 mL) was stirred for 1 h at 20 ꢀC.
(X) Y
b
Conversions and ratios determined by 11B NMR.
c
Scheme 2. Orientations of aromatic C–H borylation.
Compound 2d (1.5 equiv) was used.

T. Kikuchi et al. / Tetrahedron 64 (2008) 4967–4971
4969
Table 3
isomerically pure products are obtained even for two distinct
One-pot synthesis of biaryls via C–H borylation–cross-coupling sequencea
substituents on the arenes.7 In the case of five-membered hetero-
arenes such as furans, thiophenes, and pyrroles, the electronegative
heteroatom causes the C–H bonds at the a-positions to be active so
that borylation occurs at the a-positions.18 Thus, the regioselective
monoborylation of benzo-fused substrates is possible. In this
study, we employed such arenes that produce a single arylboronic
ester (5).
Entry
Product 6b
Yield/%c (time/h)d
Method Ae
Method Bf
93g (2)
Cl
Cl
1
96g (2)
96 (2)
87 (4)
88 (4)
93 (2)
93 (2)
6a
In one-pot, two-step reactions in which each step is catalyzed by
different metal complexes, a catalyst used in the first step often
inhibits second step. Thus, our initial efforts were focused on
finding effective reaction conditions for the second cross-coupling
step (Table 2). Pinacol 3,5-dichlorophenylborate (ca. 1.1 mmol) was
prepared in situ by the C–H borylation of 1,3-dichlorobenzene
(1.36 mmol) with pin2B2 2 (0.65 mmol) in the presence of the
1/2[Ir(OMe)(COD)]2-dtbpy catalyst (0.020 mmol) in hexane (2 mL)
at 25 ꢀC for 4 h. This solution was allowed to directly react with
bromobenzene (1.0 mmol) at 60 ꢀC for 2 h by using a variety of
palladium catalysts (0.03 mmol), bases (3 mmol), and solvents
(4 mL). Fortunately, it was found that a combination of PdCl2(dppf),
K3PO4$nH2O, and DMF works well to form the desired 3,5-
dichlorobiphenyl in 96% yield (entry 1). Use of PdCl2(PPh3)2 (entry
2) or Pd(dba)2 (entry 3) resulted in low yield due to formation of
inactive palladium-black. As for bases, K3PO4 in DMF gave the best
results among the four bases employed (entries 1 and 4–6). The
reactions were faster in polar DMF (entry 7) than in less-polar di-
oxane and hexane (entries 7 and 8). The C–H borylation of 1,3-di-
chlorobenzene (1.30 mmol) with HBpin (1.43 mmol) at 25 ꢀC for 8 h
yielded pinacol 3,5-dichlorophenylboronate (ca. 1.1 mmol). Its
cross-coupling with bromobenzene (1.0 mmol) with PdCl2(dppf),
K3PO4$nH2O in DMF was also effective for synthesis of 3,5-
dichlorobiphenyl in 93% yield (entries 9).
Representative results of one-pot synthesis of unsymmetrical
biaryls (6) via the sequential reactions involving aromatic C–H
borylation of arenes with B2pin2 (method A) or that by HBpin (1)
(method B) and the cross-coupling with bromoarenes under the
optimal conditions shown in Table 2 are summarized in Table 3. The
method provides a convenient and efficient route for preparing
a variety of biaryls. Representative bromoarenes possessing an
electron-withdrawing group, donating group, and an ortho-sub-
stituent afforded 6 in high yields (entries 1–7), while electron-rich
(entry 3) or sterically hindered bromoarene (entry 4) required
Cl
2
3
4
5
91g (2)
81 (4)
84 (8)
91 (2)
87 (2)
CO2Me
6b
Cl
Cl
OMe
6c
Cl
Cl
Me
6d
Cl
F3C
COMe
6e
NC
MeO2C
6
7
CN
6f
Cl
Cl
CO2Me
96 (2)
93 (2)
86 (2)
87 (2)
6g
Cl
8
6h
N
S
H
a
The C–H borylation of arenes with B2pin2 (method A) or HBpin (method B) to
give arylboronates (5, ca. 1.1 mmol) was followed by cross-coupling with aryl bro-
mides (1.0 mmol) at 60 ꢀC in the presence of PdCl2(dppf) (0.03 mmol), K3PO4
(3 mmol) and DMF (4 mL).
b
Left part of biaryls comes from arenes and right part from boromoarenes.
Isolated yields.
Reaction times at the cross-coupling stage.
The C–H borylation of arene (1.30–1.43 mmol) with B2pin2 (0.63–0.69 mmol)
c
d
e
Table 2
Reaction conditions for one-pot synthesis of biarylsa
was carried out for 0.5–8 h in the presence of 1/2[Ir(OMe)(COD)]2-dtbpy (3.0 mol %,
0.020 mmol).
Cl
Cl
Cl
f
B2pin2
Aromatic C–H borylation of arene (1.12–1.57 mmol) with HBpin (1.23–
Br Ph
or HBpin
1.73 mmol) was carried out for 2–8 h in the presence of 1/2[Ir(OMe)(COD)]2-dtbpy
(3.0 mol %, 0.034–0.048 mmol).
Ph
(5)
Pd catalyst
base
60 °C, 2 h
[Ir(OMe)(COD)]2
/2dtbpy
hexane, 25 °C
g
GC yields.
Cl
Entry
B2pin2 or HBpin
Pd catalyst
Base
Solvent
Yield/%b
longer reaction times to complete the cross-coupling. The C–H
borylation of 1,3-disubstituted arenes having two distinct sub-
stituents (entries 5 and 6) and 1,2-disubstituted arenes bearing
identical substituents (entry 7) generated isomerically pure aryl-
boronates and biaryls. Although a-heteroarylboronic acids such as
2-pyridineboronic acid and 2-pyrroleboronic acid are highly sus-
ceptible to hydrolytic protodeboration, the corresponding pinacol
esters are sable for such B–C bond cleavage in the presence of
a base. Thus, 2-indoleboronate generated from indole smoothly
coupled with 2-bromothiophene (entry 8). There were no signifi-
cant differences in the yields and reaction rates between method A
and method B, but high stability of B2pin2 to air and water is
convenient for handling and economical HBpin is suitable for
large-scale preparation of arylboronates and biaryls.
1
2
3
4
5
6
7
8
9
B2pin2
B2pin2
B2pin2
B2pin2
B2pin2
B2pin2
B2pin2
B2pin2
HBpin
PdCl2(dppf)
PdCl2(PPh3)2
Pd(dba)2
PdCl2(dppf)
PdCl2(dppf)
PdCl2(dppf)
PdCl2(dppf)
PdCl2(dppf)
PdCl2(dppf)
K3PO4
K3PO4
K3PO4
Cs2CO3
K2CO3
KOAc
K3PO4
K3PO4
K3PO4
DMF
DMF
DMF
DMF
DMF
DMF
Dioxane
Hexane
DMF
96
55
1
88
80
53
84
9
93
a
C–H borylation of 1,3-dichlorobenzene (1.36 mmol) with B2pin2 (0.65 mmol) in
for 4 h in the presence of 1/2[Ir(OMe)(COD)]2-dtbpy
hexane (2 mL) at 25 ꢀ
C
(3.0 mol %, 0.020 mmol) was followed by cross-coupling with bromobenzene
(1.0 mmol) at 60 ꢀC for 2 h by using Pd catalyst (0.030 mmol), base (3.0 mmol), and
solvent (4 mL).
b
GC yields based on bromobenzene.

4970
T. Kikuchi et al. / Tetrahedron 64 (2008) 4967–4971
3. Experimental
3.5. Spectral data of biaryls
3.1. Synthesis of borane–amine complexes (2)
3.5.1. Compound 6a
1H NMR (400 MHz, CDCl3): d 7.36 (t, J¼1.8 Hz, 1H), 7.40 (tt, J¼1.4
and 7.2 Hz, 1H), 7.43–7.48 (m, 2H), 7.46 (d, J¼2.0 Hz, 2H), 7.54 (dt,
J¼1.5 and 6.5 Hz, 2H); 13C NMR (100 MHz, CDCl3): d 125.64, 127.05,
127.11, 128.44, 129.01, 135.23, 138.52, 144.18; MS (EI): m/z (%) 152
(52), 186 (8), 222 ([M]þ, 100); HRMS (EI): calcd for C12H8Cl2:
222.0003; found: 222.0018.
Borane/amine complexes (2) were synthesized by the methods
of Vaultier and Brown.10 The synthesis of 2d from NaBH4, BF3$OEt2,
and PhNEt2 was carried out as follows.
To a 500-mL flask charged with NaBH4 (0.4 mol) and PhNEt2
(0.5 mol) in THF (100 mL) was dropwise added BF3$OEt2 (0.5 mol)
at ꢁ78 ꢀC. The mixture was allowed to warm slowly to room
temperature and was stirred for 1–4 h. The complete disappear-
ance of B–F species was checked by 11B NMR. The mixture was
diluted with pentane (100 mL) to precipitate NaBF4. Filtration of
solid residue through a Celite pad was followed by evaporation of
the solvent and other volatiles. Further evaporation of trace
amounts of volatiles in high vacuo (10ꢁ2 mmHg) for 16 h gave
72.5 g (89%) of 2d. 1H NMR (400 MHz, CDCl3) d 1.06 (t, J¼7.16 Hz,
6H), 1.84 (q, J¼90.3 Hz, 3H, BH3), 3.29–3.40 (m, 4H), 7.27 (t,
J¼7.34 Hz, 1H), 7.38 (t, J¼7.94 Hz, 2H), 7.65 (d, J¼8.48 Hz, 2H); 11B
NMR (128 MHz, CDCl3) d ꢁ12.0.
3.5.2. Compound 6b
1H NMR (400 MHz, CDCl3): d 3.95 (s, 3H), 7.38 (t, J¼1.8 Hz, 1H),
7.48 (d, J¼1.7 Hz, 2H), 7.60 (d, J¼8.0 Hz, 2H), 8.11 (d, J¼8.3 Hz, 2H);
13C NMR (100 MHz, CDCl3): d 52.25, 125.75, 127.02, 127.94, 130.00,
130.28, 135.46, 142.74, 142.92, 166.60; MS (EI): m/z (%) 124 (6), 151
(8), 186 (41), 249 (100), 280 ([M]þ, 62); HRMS (EI): calcd for
C14H10Cl2O2: 280.0058; found: 280.0043.
3.5.3. Compound 6c
1H NMR (400 MHz, CDCl3): d 3.84 (s, 1H), 6.96 (dt, J¼2.6 and
9.4 Hz, 2H), 7.26 (t, J¼1.8 Hz, 1H), 7.40 (d, J¼2.0 Hz, 2H), 7.45 (dt,
J¼2.6 and 9.3 Hz, 2H); 13C NMR (100 MHz, CDCl3): d 55.34, 114.40,
125.08, 126.41, 128.12, 130.88, 135.14, 143.74, 159.95; MS (EI): m/z
(%) 139 (12), 173 (6), 209 (22), 237 (28), 252 ([M]þ, 100); HRMS (EI):
calcd for C13H10Cl2O2: 252.0109; found: 252.0098.
3.2. Synthesis of pinacolborane
A
100 mL-flask, equipped with a Claisen-head distillation
apparatus, was charged with BH3$N(Ph)Et2 (2d, 75 mmol) and
tetraglyme (20 mL). A solution of pinacol (50 mmol) in tetraglyme
(5 M solution, 10 mL) was dropwise added over 30 min to the
flask cooled by a water bath (25 ꢀC). The mixture was stirred for
30 min at room temperature. Distillation in vacuo gave pina-
colborane (4.8 g, 75%). Bp 36 ꢀC/42 mmHg. 1H NMR (400 MHz,
CDCl3) d 1.27 (s, 12H), 4.10 (q, J¼168 Hz, 1H); 11B NMR (128 MHz,
CDCl3) d 28.1.
3.5.4. Compound 6d
1H NMR (400 MHz, CDCl3): d 2.26 (s, 3H), 7.16–7.31 (m, 4H), 7.21
(d, J¼1.7 Hz, 2H), 7.35 (t, J¼1.9 Hz, 1H); 13C NMR (100 MHz, CDCl3):
d 20.27, 125.98, 126.91, 127.69, 128.17, 129.41, 130.53, 134.55, 135.13,
139.12, 144.83; MS (EI): m/z (%) 165 (86), 166 (86), 201 (100), 236
([M]þ, 83); HRMS (EI): calcd for C13H10Cl2: 236.0160; found:
236.0153.
3.5.5. Compound 6e
3.3. Procedure for one-pot biaryl cross-coupling using B2pin2
(method A)
1H NMR (400 MHz, CDCl3): d 2.68 (s, 3H), 7.72 (dt, J¼1.9 and
8.4 Hz, 2H), 7.95 (s, 1H), 8.10 (s, 2H), 8.12 (dt, J¼1.5 and 8.3 Hz, 2H);
13C NMR (100 MHz, CDCl3): d 26.64, 114.19, 117.06, 122.73 (q, J
(CF)¼1086 Hz), 127.35, 128.06, 128.06 (q, J (CF)¼26.4 Hz), 129.26,
132.66 (q, J (CF)¼135 Hz), 133.80, 137.27, 141.48, 142.31, 197.20; MS
(EI): m/z (%) 177 (13), 226 (18), 246 (13), 274 (100), 289 ([M]þ, 24);
HRMS (EI): calcd for C16H10F3NO: 289.0714; found: 289.0737.
A 25-mL flask equipped with a magnetic stirring bar, a septum
19
inlet, and
a condenser was charged with [Ir(OMe)(COD)]2
(0.01 mmol), 4,40-di-tert-butyl-2,20-bipyridine (dtbpy, 0.02 mmol),
and bis(pinacolato)diboron (B2pin2, 0.65 mmol) and then flushed
with nitrogen. Hexane (2 mL) and 1,3-dichlorobenzene (1.36 mmol)
were added, and the mixture was then stirred at 25 ꢀC for 4 h to
give pinacol 3,5-dichlorophenylboronate (ca. 1.1 mmol). To this
solution were added PdCl2(dppf) (0.030 mmol), K3PO4$nH2O
(3 mmol), and DMF (4 mL), and the mixture was stirred at 60 ꢀC for
2 h. The formation of methyl 4-(3,5-dichlorophenyl)benzoate (2b)
in 96% yield was analyzed by GC and GC mass spectroscopy. The
product was extracted with benzene, washed with brine, and dried
over MgSO4. Chromatography over silica gel (hexane/AcOEt) gave
analytically pure 2b.
3.5.6. Compound 6f
1H NMR (400 MHz, CDCl3): d 3.97 (s, 3H), 7.71 (d, J¼8.1 Hz, 2H),
7.76 (t, J¼2.0 Hz, 1H), 7.78 (d, H¼8.6 Hz, 2H), 8.07 (t, J¼1.6 Hz, 1H),
8.15 (t, J¼1.5 Hz, 1H); 13C NMR (100 MHz, CDCl3): d 52.64, 112.10,
118.46, 126.50, 127.78, 129.43, 131.39, 132.81, 135.36, 141.07, 143.08,
165.43; MS (EI): m/z (%) 149 (23), 177 (70), 212 (13), 240 (100), 271
([M]þ, 63); HRMS (EI): calcd for C15H10ClNO2: 271.0400; found:
271.0394.
3.5.7. Compound 6g
3.4. Procedure for one-pot biaryl cross-coupling using HBpin
(method B)
1H NMR (400 MHz, CDCl3): d 3.95 (s, 3H), 7.44 (dd, J¼2.1 and
8.4 Hz, 1H), 7.53 (d, J¼8.3 Hz, 1H), 7.61 (d, J¼8.3 Hz, 2H), 7.70 (d,
J¼2.2 Hz, 1H), 8.11 (d, J¼8.0 Hz, 2H); 13C NMR (100 MHz, CDCl3):
d 52.22, 126.42, 126.87, 129.06, 129.68, 130.26, 130.84, 132.39,
133.08, 139.92, 142.99, 166.66; MS (EI): m/z (%) 124 (12), 151 (11),
186 (51), 249 (100), 280 ([M]þ, 70); HRMS (EI): calcd for
A 25-mL flask equipped with a magnetic stirring bar, a septum
19
inlet, and
(0.02 mmol)
a
condenser was charged with [Ir(OMe)(COD)]2
and
4,40-di-tert-butyl-2,20-bipyridine
(dtbpy,
0.04 mmol) and then flushed with nitrogen. Hexane (2 mL), pina-
colborane (HBpin, 1.43 mmol), and 1,3-dichlorobenzene (1.3 mmol)
were then added, and the mixture was stirred at 25 ꢀC for 8 h to
give pinacol 3,5-dichlorophenylboronate (ca. 1.1 mmol). The solu-
tion thus obtained was directly subjected to cross-coupling under
the same conditions as those in the procedures described in
Section 3.3.
C14H10Cl2O2: 280.0058; found: 280.0055.
3.5.8. Compound 6h
1H NMR (400 MHz, CDCl3): d 6.73 (s, 1H), 7.09 (t, J¼4.3 Hz,
1H), 7.11 (t, J¼8.4 Hz, 1H), 7.19 (t, J¼7.1 Hz, 1H), 7.26 (d, J¼5.1 Hz, 1H),
7.28 (d, J¼5.1 Hz, 1H), 7.37 (d, J¼7.8 Hz, 1H), 7.59 (d, J¼7.8 Hz, 1H),
8.22 (br s, 1H); 13C NMR (100 MHz, CDCl3): d 100.37, 110.74, 120.41,

T. Kikuchi et al. / Tetrahedron 64 (2008) 4967–4971
4971
6. (a) Iverson, C. N.; Smith, M. R., III. J. Am. Chem. Soc. 1999, 121, 7696–7697; (b)
Cho, J.-Y.; Iverson, C. N.; Smith, M. R., III. J. Am. Chem. Soc. 2000, 122, 12868–
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122.87, 124.56, 127.87, 129.04, 132.29, 135.58, 136.46; MS (EI): m/z
(%) 100 (9), 127 (5), 154 (9), 171 (9), 199 ([M]þ, 100); HRMS (EI):
calcd for C12H9NS: 199.0452; found: 199.0456.
7. (a) Ishiyama, T.; Miyaura, N. J. Organomet. Chem. 2003, 680, 3–11; (b) Ishiyama,
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This work was supported by Grant-in-Aid for Scientific Research
on Priority Areas (No. 17065001, ‘Advanced Molecular Trans-
formations of Carbon Resources’) from Ministry of Education, Cul-
ture, Sports, Science and Technology, Japan.
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