Tandem Sonogashira-Hagihara coupling/cycloisomerization reactions of ethynylboronic acid MIDA ester to afford 2-heterocyclic boronic acid MIDA esters: A concise route to benzofurans, indoles, furopyridines and pyrrolopyridines

Article abstract of DOI:10.3987/COM-17-13723

A one-pot process that provides direct access to 2-heterocyclic MIDA (N-methyliminodiacetic acid) boronates has been developed. The reaction of 2-iodophenols or 2-iodoanilines with ethynylboronic acid MIDA ester readily afforded 2-substituted heterocyclic compounds. Amidine and phosphazene bases, especially TMG (1,1,3,3-tetramethylguanidine) assumed an important role in the tandem Sonogashira-Hagihara coupling/cycloisomerization reactions.

Full text of DOI:10.3987/COM-17-13723

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HETEROCYCLES, Vol. 94, No. 7, 2017
HETEROCYCLES, Vol. 94, No. 7, 2017, pp. 1322 - 1336. © 2017 The Japan Institute of Heterocyclic Chemistry
Received, 14th April, 2017 , Accepted, 19th May, 2017, Published online, 9th June, 2017
DOI: 10.3987/COM-17-13723
TANDEM
SONOGASHIRA-HAGIHARA
COUPLING/CYCLO-
ISOMERIZATION REACTIONS OF ETHYNYLBORONIC ACID MIDA
ESTER TO AFFORD 2-HETEROCYCLIC BORONIC ACID MIDA
ESTERS: A CONCISE ROUTE TO BENZOFURANS, INDOLES,
FUROPYRIDINES AND PYRROLOPYRIDINES
Yohji Sakurai*
Medicinal Chemistry Research Institute, Otsuka Pharmaceutical Co., Ltd., 463-10
Kagasuno, Kawauchi-cho, Tokushima, 771-0192, Japan
E-mail: Sakurai.Yohji@otsuka.jp
Abstract – A one-pot process that provides direct access to 2-heterocyclic MIDA
(N-methyliminodiacetic acid) boronates has been developed. The reaction of
2-iodophenols or 2-iodoanilines with ethynylboronic acid MIDA ester readily
afforded 2-substituted heterocyclic compounds. Amidine and phosphazene bases,
especially TMG (1,1,3,3-tetramethylguanidine) assumed an important role in the
tandem Sonogashira-Hagihara coupling/cycloisomerization reactions.
The palladium-catalyzed coupling reaction of organoboronic acids with organic halides, i.e., the
Suzuki-Miyaura coupling, is one of the most efficient and reliable reactions in the synthesis of many
natural products, pharmaceuticals and organic materials.1 My research has focused on the development of
a novel synthetic procedure for N-methyliminodiacetic acid (MIDA) boronates, which were developed by
Burke et al., to synthesize benzofuran and indole derivatives.2 Benzofuran and indole nucleus are
ubiquitous framework found in many natural products and pharmaceuticals; therefore, the development of
an efficient and versatile synthetic methodology to obtain these classes of compounds would be of great
value.3
As a one of the new approach to aim the platform, tandem Sonogashira-Hagihara coupling4/
cycloisomerization reactions of ethynylboronic acid MIDA ester to afford 2-heterocyclic boronic acid
MIDA esters were investigated. Although the Sonogashira-Hagihara reaction is a useful method to access
heterocyclic compounds,5 cross-coupling of halide with ethynylboronic acid MIDA ester has been limited.
A two-step procedure (the Sonogashira-Hagihara coupling followed by the gold-catalyzed

HETEROCYCLES, Vol. 94, No. 7, 2017
1323
cycloisomerization) has been described by Toste et al.6 A prognosis that the modification of reaction
conditions in the Sonogashira-Hagihara reaction might afford 2-heterocyclic boronic acid MIDA esters in
a one-pot process led the investigation. Recently, Watson’s group published a one-pot reaction of
ethynylboronic acid MIDA ester to afford 2-heterocyclic boronic acid MIDA esters using
Cu(I)/Pd(O)/Cu(II) catalysis and inorganic base.7
N
N
Au
O
B
N
CuI, PdCl2(Ph3P)2
Et3N, DMF, rt
I
O
O
B
O
B
+
O
O
O
O
Y
O
YH
O
O
O
YH
Toste's work
N
Y = O, NTs
N
I
O
CuI
Pd0
CuII
B
O
B
R
R
+
O
O
X
XH
O
O
O
O
X = O, NTs
CuI, PdCl2(Ph3P)2, Cu(OAc)2, K3PO4 or K2CO3, DMF
Watson's work
NH
N
I
N
Me2N NMe
2, CuI
O
B
O
R
B
+
R
O
O
Z
ZH
O
PdCl2(Ph3P)2, Ph3P, DMF
50~70 oC
O
O
O
Z = O, NTs, NNs
This work
Scheme 1. Approaches towards 2-heterocyclic boronic acid MIDA esters
Herein I present an alternative one-pot synthesis of 2-heterocyclic boronic acid MIDA esters which
provides efficient access to benzofurans, indoles, furopyridines and pyrrolopyridines. This reaction is
using an amidine base and without Cu(II) salt, which fulfills a consequential role to led the ring closure in
the Watson’s report.
In the initial model experiment, as shown in Table 1, methyl 4-hydroxy-3-iodobenzoate (1) or
4-chloro-2-iodophenol (2) was treated with ethynylboronic acid MIDA ester in the presence of
PdCl2(Ph3P)2 and CuI. Table 1 summarizes the isolated yield of boronic acid MIDA ester under these
reaction conditions. Although use of 1.6 equiv of Et3N, a commonly used base in the
Sonogashira-Hagihara reaction, afforded a small amount of coupling/cyclization product (1A) on LC-MS,
1A was not isolated due to low conversion (entry 1a). Alternatively, replacement of Et3N with
1,1,3,3-tetramethylguanidine (TMG), which has been effective in the tandem coupling/
cycloisomerization reaction of aliphatic or aromatic terminal alkynes in the solid-phase synthesis of
indoles, was considered.8 To my delight, 1A and 2A were obtained in 26% and 13% yield, respectively
(entries 1b, 2a). Increasing the amount of TMG to 3.0 equiv impaired the reaction (entry 2b), while

1324
HETEROCYCLES, Vol. 94, No. 7, 2017
decreasing the amount of TMG to 1.2 equiv resulted in improved yield (entries 1d, 2c). A higher yield
was observed in DMF compared to dioxane (entries 1c, 2g).
Next, the effect of additive was investigated to avoid consumption of terminal ethynyl compound during
the reduction of Pd(II) to Pd(0). The addition of Ph3P (0.1 equiv) increased the yield to 27% (entry 2d);
however 0.3 equiv of Ph3P complicated the reaction and made isolation of 2A difficult (entry 2e).
Although the effect of Ph3P was limited, using a small excess of ethynylboronic acid MIDA ester
enhanced the yield (entries 1e and 2h, based on 1 or 2).
Under the optimized conditions, 1.3 equiv of ethynylboronic acid MIDA ester, 0.1 equiv of Ph3P and 1.2
equiv of base in DMF, 2-tert-butylimino-2-dimethylamino-1,3-dimethylperhydro-1,3,2-diazaphosphorine
(BEMP; a phosphazene base) or 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU; an amidine base) afforded 1A
in 34% and 64% yield, respectively (entries 1f and 1g). While the use of Et3N afforded a small amount of
the MIDA boronate on LC-MS, 1A was not isolated due to low conversion (entry 1h). The uncyclized
Sonogashira-Hagihara product intermediate was also detected on LC-MS, but was small in amount. The
choice of base plays an important role in the tandem Sonogashira-Hagihara coupling/cycloisomerization
reactions of ethynylboronic acid MIDA ester.
Table 1. Optimization of the reaction conditions for the synthesis of benzofuran-2-MIDA boronatesa
I
N
Base, CuI, PdCl2(Ph3P)2
solvent, 50 oC
N
+
O
O
B
R
B
R
O
O
O
OH
O
O
O
O
Entry
Substrate
MIDA
ester (eq)
Base (eq)
Ph3P
(eq)
Solvent
Product
Yieldb
(%)
c
1a
1b
1c
1d
1e
1f
1g
1h
2a
2b
2c
2d
2e
2f
1.0
1.0
1.0
1.0
1.3
1.3
1.3
1.3
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.3
Et3N (1.6)
TMG (1.6)
TMG (1.6)
TMG (1.2)
TMG (1.2)
BEMP (1.2)
DBU (1.2)
Et3N (1.2)
TMG (1.6)
TMG (3.0)
TMG (1.2)
TMG (1.6)
TMG (1.6)
TMG (1.2)
TMG (1.2)
TMG (1.2)
DMF
DMF
dioxane
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
dioxane
DMF
-
-
-
0.1
0.1
0.1
0.1
0.1
-
-
26
15
45
75
34
64
O
O
N
O
I
O
B
O
O
O
O
OH
O
1
1A
c
-
13
c
-
-
-
44
27
Cl
I
N
Cl
0.1
0.3
0.1
0.1
0.1
O
B
OH
O
O
c
O
-
O
2
2A
52
40
87
2g
2h
a Reaction conditions: 2.0 mmol of 1 or 2, 10 mol% of CuI, 5 mol% of PdCl2(Ph3P)2, 6.0 mL solvent, 50 °C, N2
atmosphere, 22 h. b Isolated yields. c Not isolated due to low conversion.

HETEROCYCLES, Vol. 94, No. 7, 2017
1325
Table 2. The reaction of 2-iodophenols and ethynylboronic acid MIDA estera
NH
NMe2
Me2N
N
N
, CuI
I
O
B
O
B
R
+
R
O
O
O
OH
PdCl2(Ph3P)2, Ph3P, DMF
50~70 oC
O
O
O
O
Entry
1
ArI
Yieldb
(%)
Product
Entry
9
ArI
Yieldb
(%)
Product
O
O
I
75
20
N
B
N
I
42c
O
O
O
O
B
OH
O
O
O
O
O
O
OH
O
O
9
1A
I
Cl
I
2
3
4
87
60
73
10
11
12
12
N
Cl
N
25c
O
B
O
B
O
OH
OH
O
O
O
10
O
O
O
O
2A
70c
I
N
N
I
O
B
O
OH
B
O
O
O
O
11
O
OH
O
O
O
3
I
I
N
45
N
N
N
43c
O
O
B
O
B
O
OH
OH
O
O
O
O
O
O
O
O
O
O
4
12
41d
60d
N
N
I
I
5
6
47
68
13
14
N
B(OH)2
B(OH)2
N
O
B
O
Cl
OH
O
OH
O
Cl
13
O
O
5
I
O2N
I
N
O2N
O
O
14
N
B
OH
OH
O
O
6
O
O
I
I
7
8
36
15
16
34c,e
N
O
H
O
O
B
N
H
O
O
H
OH
N
OH
O
O
15
O
O
7
26c
7c,e
O2N
O
H
O2N
I
S
N
I
O
O
16
N
B
N
N
OH
O
O
OMe
OH
OMe
O
O
8
a General reaction conditions: 1 equiv of aryl iodide (2.0 mmol), 1.3 equiv of ethynylboronic acid MIDA ester, 10
mol% of CuI, 5 mol% of PdCl2(Ph3P)2, 10 mol% of Ph3P, 1.2 equiv of TMG, 6.0 mL DMF, 50 °C, 22 h. b Isolated
c
d
yields. Reaction conducted at 70 °C. 1 : 1 mixture of the MIDA boronate and boronic acid was obtained. The
e
mixture was converted to the boronic acid by treatment with EtOH. As MIDA boronate was difficult to isolate,
yield was determined by the following arylation reaction of crude MIDA boronate.
The optimized conditions were applied to a variety of phenols and pyridinols to examine the versatility of
this methodology. As demonstrated in Table 2, substrates bearing different functional groups were
tolerant of the reaction conditions and provided the corresponding products with moderate to high
isolated yields. When the uncyclized Sonogashira-Hagihara product intermediate remained at 50 °C, the
reaction was conducted at 70 °C. The temperature range between 50 °C and 70 °C was determined to be
suitable for this reaction, as higher reaction temperatures often caused reduction in yield. While
2-iodopyridin-3-ol cleanly afforded the corresponding MIDA boronate in 45% yield (entry 12),

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HETEROCYCLES, Vol. 94, No. 7, 2017
3-iodopyridin-4-ol and 4-iodopyridinol afforded 1 : 1 mixtures of the MIDA boronate and boronic acid
after column chromatography (eluent, CH2Cl2 : MeOH = 10 : 1). The mixtures were converted to the
boronic acid by treatment with EtOH (entries 13 and 14). The MIDA boronate and boronic acid prepared
from 3-iodopyridin-2-ol were difficult to isolate; therefor the crude MIDA boronate were converged to
2-aryl derivatives by Lipshutz’s method (entries 15 and 16).9
Table 3. The reaction of 2-iodoanilines and ethynylboronic acid MIDA estera
NH
I
N
N
NMe2, CuI
Me2N
O
R
O
B
+
R
B
O
O
Z
ZH
PdCl2(Ph3P)2, Ph3P, DMF
50~70 oC
O
O
O
O
Z = NTs, NNs
Entry
1
ArI
Yieldb
(%)
Product
Entry
7
ArI
Yieldb
(%)
Product
F3C
I
I
81
50
N
F3C
MeO
MeO
N
O
B
N
O
B
NHTs
O
O
NHTs
N
Ts
O
O
O
O
Ts
23
17
15c
70d
8
9
45
MeO
MeO
I
2
3
I
N
O
N
Ns
B
O
NHTs
N
NHNs
O
18
O
24 Ts
I
I
18
N
N
40d
O
O
B
B
NHNs
O
O
NHBoc
N
O
O
O
O
Ns
25
NHBoc
19
Cl
I
I
4
5
6
69
61
85
10
11
12
16
18e
56d
N
N
Cl
O
O
B
B
N
N
NHTs
NHTs
O
O
N
N
Ts
N
26
O
O
O
O
Ts
N
20
O
I
O
46
N
N
I
O
O
B
O
O
O
B
NHTs
N
O
N
Ts
O
O
O
NHTs
O
O
27
Ts
21
15d
I
I
N
N
O
O
B
N
B
NHTs
O
N
NHNs
O
O
N
N
Ns
O
O
O
O
O
O
Ts
22
28
a General reaction conditions: 1 equiv of aryl iodide (2.0 mmol), 1.3 equiv of ethynylboronic acid MIDA ester, 10
mol% of CuI, 5 mol% of (Ph3P)2PdCl2, 10 mol% of Ph3P, 1.2 equiv of TMG, 6.0 mL DMF, 50 °C, 22 h. b Isolated
c
yields. As MIDA boronate was difficult to isolate, yield was determined by the following arylation reaction of
crude MIDA boronate. d Reaction conducted at 70 °C. e Using 1.6 equiv of ethynylboronic acid MIDA ester.
The reaction was also found to be effective in anilines, as shown in Table 3. The protecting group of
2-iodoaniline was screened. Although tosylated and nosylated anilines afforded corresponding
indole-2-MIDA boronate, N-Boc derivative did not provide the indole product; the uncyclized alkyne was
obtained even after heating at 70 °C (Table 3, entries 1~3). Isolation of N-nosylated indole-2-boronic acid
MIDA ester by chromatography or recrystallization was problematic; therefore the crude MIDA boronate

HETEROCYCLES, Vol. 94, No. 7, 2017
1327
was used in the subsequent arylation.9 2-Iodoanilines afforded cyclized MIDA boronates as well as
2-iodophenols via tandem Sonogashira-Hagihara coupling/cycloisomerization reactions of ethynyl-
boronic acid MIDA ester.
The obtained MIDA boronates were examined to determine if these serve as the intermediate in the
synthesis of 2-substituted heterocyclic compounds.10 The preliminary results of Suzuki-Miyaura coupling
reaction are summarized in Table 4. In the case of N-nosylindole derivatives, a significant amount of the
reduced product at 2-position were obtained in addition to the coupled product (Table 4, entry 26).
Table 4. Suzuki-Miyaura coupling reactions of MIDA boronates in Lipshutz’s conditionsa
N
(dtbpf)PdCl2, Et3N
O
B
+
Ar
R
Ar X
R
O
Z
Z
2 wt% TPGS-750 M/H2O
O
O
Entry
1
Product
X
Entry
15
Product
X
(Yield%)b
(Yield%)b
O
O
N
Br (72)
Br (72)
N
N
O
S
O
O
O
O
N
2
3
4
Br (86)c
Br (94)
16
17
18
Br (63)
Br (41)d
Br (43)d
O
S
O
Br (76)
Cl (28)
O
N
O
O
O
O
N
N
O
O
O
N
Cl
5
6
7
Br (96)
I (66)
19
20
21
Br (80)
Br (82)
Br (92)
S
N
O
O
Tos
Br (85)
N
Cl
Tos
Cl
Br (87)
N
S
O
N
Tos
O
O
8
9
Br (94)
Br (71)
22
23
Br (30)
Br (63)
H
O
MeO
O
N
Tos
MeO
F3C
N
O
Tos
10
11
Br (44)
Br (50)
24
25
Br (68)
Br (45)
O
N
Tos
MeO
S
N
Tos
O
N
continued
continued

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HETEROCYCLES, Vol. 94, No. 7, 2017
Br (33)e
O
MeO
12
Br (77)
26
S
H
N
N
Ns
O
OMe
O2N
N
13
14
Br (87)
Br (74)
27
28
Br (46)
Br (32)
N
N
O
Tos
N
N
O
Tos
a
General reaction conditions: 1 equiv of MIDA boronate (0.60 mmol), 1 equiv of aryl halide, 8 mol% of
b
c
(dtbpf)PdCl2, 1.5 mL of 2 wt% TPGS-750M H2O, 3 equiv of Et3N, 40 °C, 22 h. Isolated yields. Reaction
conducted at room temperature. Corresponding boronic acid was used. 57% of 5-methoxy-N-Ns-indole was
d
e
obtained.
EXPERIMENTAL
General. All reagents and anhydrous solvents were purchased from commercial suppliers and used
without further purification. All reactions were performed under a nitrogen atmosphere. Automated flash
1
chromatography was performed on YAMAZEN UV-10VW with peak detection at 254 nm. H (400
MHz) NMR spectra were recorded on a Bruker AvanceIII 400. For 1H-NMR spectroscopy,
tetramethylsilane (δ = 0 ppm) in served as an internal standard. High-resolution MS data were obtained
on a Thermo Scientific LTQ Orbitrap XL. High-resolution MS spectral analysis was performed on a
Xcalibur. Melting points were uncorrected. IR spectra were recorded on a HORIBA FT-720.
Typical procedure for the synthesis of 2-benzofuranboronic acid MIDA esters. 5-Methoxy-
carbonylbenzofuran-2-MIDA boronate (1A). Dry DMF (6.0 mL) was added to methyl 4-hydroxy-3-
iodobenzoate (0.56 g, 2.0 mmol), ethynylboronic acid MIDA ester (0.47 g, 2.6 mmol), CuI (38 mg, 0.20
mmol), PdCl2(Ph3P)2 (70 mg, 0.10 mmol) and Ph3P (52 mg, 0.20 mmol) under N2. 1,1,3,3-Tetramethyl-
guanidine (TMG) (0.30 mL, 2.4 mmol) was added to the resulting solution under N2. The reaction
mixture was stirred at 50 °C for 22 h under N2. The resulting mixture was diluted with water to form a
precipitate, which was filtered, washed with water and dried at room temperature. The obtained solid was
dissolved in acetone and purified by flash chromatography (SiO2, CH2Cl2 : MeOH = 10 : 1). The eluted
material was washed with hot EtOH and dried to give 1A (493.6 mg, 75%) as a pale brown solid; mp
209-212 °C (Dec.); IR (cm-1) 1749, 1712, 1558, 1508, 1437, 1352, 1292, 1232, 1188, 1138, 1089, 1038;
1H-NMR (DMSO-d6) δ 2.72 (s, 3H), 3.87 (s, 3H), 4.20 (d, J = 17.0 Hz, 2H), 4.44 (d, J = 17.0 Hz, 2H),
7.24 (d, J = 1.0 Hz, 1H), 7.69 (d, J = 8.5 Hz, 1H), 7.93 (dd, J = 1.5 Hz, 8.5 Hz, 1H), 8.34 (d, J = 1.5 Hz,
1H); Anal. Calcd for C15H14NO7B•1/4H2O (C, H, N) (53.68, 4.35, 4.17). Found (53.42, 4.03, 4.20);
HRMS calcd for C15H15NO7N [M+H] 332.0936, found 332.0936 (Δ 0.04).
5-Chlorobenzofuran-2-MIDA boronate (2A): Prepared from 4-chloro-2-iodophenol and ethynyl-
boronic acid MIDA ester. Purification by flash chromatography (AcOEt) afforded 2A (533.5 mg, 87%) as
a pale yellow solid; mp 214-218 °C (Dec.); IR (cm-1) 1749, 1558, 1446, 1363, 1282, 1228, 1138, 1092,

HETEROCYCLES, Vol. 94, No. 7, 2017
1329
1
1045, 1001; H-NMR (DMSO-d6) δ 2.70 (s, 3H), 4.19 (d, J = 17.0 Hz, 2H), 4.43 (d, J = 17.0 Hz, 2H),
7.08 (brs, 1H), 7.32 (dd, J = 2.0 Hz, 8.5 Hz, 1H), 7.61 (d, J = 8.5 Hz, 1H), 7.74 (d, J = 2.0 Hz, 1H); Anal.
Calcd for C13H11NO5BCl•1/4H2O (C, H, N) (50.05, 3.71, 4.48). Found (50.26, 3.80, 4.40); HRMS calcd
for C13H11NO5BCl [M] 307.0413, found 307.0416 (Δ 0.32).
Benzofuran-2-MIDA boronate (3): Prepared from methyl 4-hydroxy-3-iodobenzoate and ethynyl-
boronic acid MIDA ester. Purification by flash chromatography (AcOEt) afforded 3 (327.4 mg, 60%) as a
pale yellow solid; IR (cm-1) 1749, 1558, 1515, 1456, 1373, 1338, 1232, 1138, 1047; 1H-NMR (DMSO-d6)
δ 2.69 (s, 3H), 4.18 (d, J = 17.0 Hz, 2H), 4.42 (d, J = 17.0 Hz, 2H), 7.08 (d, J = 1.0 Hz, 1H), 7.20-7.25 (m,
1H), 7.27-7.32 (m, 1H), 7.55-7.59 (m, 1H), 7.63-7.67 (m, 1H); HRMS calcd for C13H13NO5B [M+H]
274.0881, found 274.0879 (Δ 0.21).
6-Methoxycarbonylbenzofuran-2-MIDA boronate (4): Prepared from 3-hydroxy-4-iodobenzoate and
ethynylboronic acid MIDA ester. Purification by flash chromatography (AcOEt) and washing with hot
EtOH afforded 4 (481.8 mg, 73%) as a pale brown solid; mp 270-273 °C (Dec.); IR (cm-1) 1749, 1707,
1431, 1346, 1298, 1217, 1149, 1053; 1H-NMR (DMSO-d6) δ 2.71 (s, 3H), 3.88 (s, 3H), 4.20 (d, J = 17.0
Hz, 2H), 4.44 (d, J = 17.0 Hz, 2H), 7.20 (d, J = 1.0 Hz, 1H), 7.78 (d, J = 8.0 Hz, 1H), 7.86 (dd, J = 1.5 Hz,
8.0 Hz, 1H), 8.34 (d, J = 1.5 Hz, 1H); Anal. Calcd for C15H14NO7B•1/4H2O (C, H, N) (53.68, 4.35, 4.17).
Found (53.42, 4.10, 4.26); HRMS calcd for C15H15NO7B [M+H] 332.0936, found 332.0938 (Δ 0.23).
6-Chlorobenzofuran-2-MIDA boronate (5): Prepared from 5-chloro-2-iodophenol and ethynylboronic
acid MIDA ester. Purification by flash chromatography (AcOEt) and washing with hot EtOH afforded 5
(290.3 mg, 47%) as a pale brown solid; mp 189-191 °C (Dec.); IR (cm-1) 1749, 1558, 1458, 1373, 1261,
1
1217, 1146, 1055; H-NMR (DMSO-d6) δ 2.69 (s, 3H), 4.18 (d, J = 17.0 Hz, 2H), 4.43 (d, J = 17.0 Hz,
2H), 7.11 (d, J = 1.0 Hz, 1H), 7.28 (dd, J = 2.0 Hz, 8.5 Hz, 1H), 7.67 (d, J = 8.5 Hz, 1H), 7.22-7.74 (m,
1H); Anal. Calcd for C13H11NO5BCl•1/8H2O (C, H, N) (50.41, 3.66, 4.52). Found (50.17, 3.41, 4.66);
HRMS calcd for C13H11NO5BCl [M] 307.0413, found 307.0413 (Δ 0.04).
5-Nitrobenzofuran-2-MIDA boronate (6): Prepared from 2-iodo-4-nitrophenol and ethynylboronic acid
MIDA ester. Purification by flash chromatography (AcOEt) afforded 6 (434.9 mg, 68%) as a pale yellow
solid; mp 232-236 °C (Dec.); IR (cm-1) 2376, 2310, 1743, 1522, 1458, 1348, 1277, 1230, 1144, 1047,
1001; 1H-NMR (DMSO-d6) δ 2.73 (s, 3H), 4.22 (d, J = 17.0 Hz, 2H), 4.46 (d, J = 17.0 Hz, 2H), 7.33 (d, J
= 0.5 Hz, 1H), 7.82 (d, J = 9.0 Hz, 1H), 8.21(dd, J = 2.5 Hz, 9.0 Hz, 1H), 8.66 (d, J = 2.5 Hz, 1H); Anal.
Calcd for C13H11N2O7B (C, H, N) (49.09, 3.49, 8.81). Found (48.99, 3.37, 8.53); HRMS calcd for
C13H11N2O7B [M] 318.0654, found 318.0648 (Δ 0.59).
6-Carbaldehydebenzofuran-2-MIDA boronate (7): Prepared from 3-hydroxy-4-iodobenzaldehyde and
ethynylboronic acid MIDA ester. Purification by flash chromatography (AcOEt) and washing with hot
EtOH afforded 7 (214.9 mg, 36%) as a pale brown solid; mp 192-196 °C (Dec.); IR (cm-1) 1757, 1682,

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1610, 1558, 1458, 1273, 1225, 1196, 1142, 105; 1H-NMR (DMSO-d6) δ 2.72 (s, 3H), 4.21 (d, J = 17.0 Hz,
2H), 4.45 (d, J = 17.0 Hz, 2H), 7.24 (d, J = 1.0 Hz, 1H), 7.80 (dd, J = 1.0 Hz, 8.0 Hz, 1H), 7.86 (d, J = 8.0
Hz, 1H), 8.12 (brs, 1H), 10.07 (s, 1H); Anal. Calcd for C14H12NO6B (C, H, N) (55.85, 4.02, 4.65). Found
(55.67, 4.11, 4.37); HRMS calcd for C14H12NO6B [M] 301.0752, found 301.0751 (Δ 0.15).
5-Carbaldehyde-7-methoxy-benzofuran-2-MIDA boronate (8): Prepared from 5-iodovanillin and
ethynylboronic acid MIDA ester. Purification by flash chromatography (AcOEt) and washing with hot
EtOH afforded 8 (174.1 mg, 26%) as a pale brown solid; mp 229-231 °C (Dec.); IR (cm-1) 1755, 1689,
1597, 1464, 1335, 1296, 1232, 1144, 1049, 1009; 1H-NMR (DMSO-d6) δ 2.72 (s, 3H), 4.01 (s, 3H), 4.20
(d, J = 17.5 Hz, 2H), 4.44 (d, J = 17.5 Hz, 2H), 7.27 (s, 1H), 7.38 (d, J = 1.5 Hz, 1H), 7.91 (d, J = 1.5 Hz,
1H), 10.01 (s, 1H); Anal. Calcd for C15H14NO7B (C, H, N) (54.42, 4.26, 4.23). Found (54.29, 4.08, 4.17);
HRMS calcd for C13H15NO7B [M+H] 332.0936, found 332.0935 (Δ 0.12).
5-Methylbenzofuran-2-MIDA boronate (9): Prepared from 2-iodo-4-methylbenzoate and ethynyl-
boronic acid MIDA ester. Purification by flash chromatography (AcOEt : hexane = 1 : 1) and washing
with hot EtOH afforded 9 (242.4 mg, 42%) as a pale brown solid; mp 200-204 °C (Dec.); IR (cm-1) 1747,
1566, 1456, 1336, 1284, 1228, 1167, 1120, 1041; 1H-NMR (DMSO-d6) δ 2.38 (s, 3H), 2.67 (s, 3H), 4.17
(d, J = 17.0 Hz, 2H), 4.41 (d, J = 17.0 Hz, 2H), 6.99 (d, J = 1.0 Hz, 1H), 7.10 (dd, J = 1.5 Hz, 8.5 Hz, 1H),
7.40-7.46 (m, 2H); Anal. Calcd for C14H14NO5B•1/4H2O (C, H, N) (57.67, 5.01, 4.80). Found (57.46,
4.94, 4.85); HRMS calcd for C14H14NO5B [M] 287.0960, found 287.0955 (Δ 0.56).
6,7-Dihydro-5H-indeno[5,6-b]furan-2-MIDA boronate (10): Prepared from 6-iodo-5-hydroxyindane
and ethynylboronic acid MIDA ester. Purification by flash chromatography (AcOEt) and washing with
hot EtOH afforded 10 (154.6 mg, 25%) as a pale yellow solid; mp 217-220 °C (Dec.); IR (cm-1) 1743,
1558, 1516, 1458, 1417, 1373, 1338, 1288, 1232, 1146, 1036; 1H-NMR (DMSO-d6) δ 2.01-2.10 (m, 2H),
2.66 (s, 3H), 2.85-2.95 (m, 4H), 4.16 (d, J = 17.0 Hz, 2H), 4.40 (d, J = 17.0 Hz, 2H), 6.96 (d, J = 0.5 Hz,
1H), 7.38 (s, 1H), 7.41 (s, 1H); HRMS calcd for C16H16NO5 [M] 313.1116, found 313.112 (Δ 0.43).
5-Phenylbenzofuran-2-MIDA boronate (11): Prepared from 4-chloro-2-iodophenol and ethynylboronic
acid MIDA ester. Purification by flash chromatography (CH2Cl2 : MeOH = 10 : 1) afforded 11 (487.7 mg,
70%) as a pale brown solid; mp 195-200 °C (Dec.); IR (cm-1) 1745, 1571, 1450, 1336, 1281, 1232, 1176,
1
1138, 1041; H-NMR (DMSO-d6) δ 2.72 (s, 3H), 4.20 (d, J = 17.0 Hz, 2H), 4.44 (d, J = 17.0 Hz, 2H),
7.13 (d, J = 1.0 Hz, 1H), 7.32-7.38 (m, 1H), 7.43-7.50 (m, 2H), 7.58 (dd, J = 2.0 Hz, 8.5 Hz, 1H),
7.63-7.71 (m, 3H), 7.91 (d, J = 1.5 Hz, 1H); Anal. Calcd for C19H16NO5B•1/2H2O (C, H, N) (63.72, 4.78,
3.91). Found (63.88, 4.34, 3.53); HRMS calcd for C19H16NO5B [M] 349.1116, found 349.1114 (Δ 0.25).
Furo[2,2-b]pyridine-2-MIDA boronate (12): Prepared from 3-hydroxy-2-iodopyridine and ethynyl-
boronic acid MIDA ester. Purification by flash chromatography (AcOEt) afforded 12 (248.4 mg, 45%) as
a pale yellow solid; mp 216-220 °C (Dec.); IR (cm-1) 3178, 1739, 1646, 1558, 1516, 1456, 1417, 1373,

HETEROCYCLES, Vol. 94, No. 7, 2017
1331
1338, 1279, 1216, 1049, 1005; 1H-NMR (DMSO-d6) δ 2.72 (s, 3H), 4.21 (d, J = 17.0 Hz, 2H), 4.45 (d, J
= 17.0 Hz, 2H), 7.21 (d, J = 1.0 Hz, 1H), 7.33 (dd, J = 4.5 Hz, 8.5 Hz, 1H), 7.98-8.04 (m, 1H), 8.51 (brd,
J = 4.0 Hz, 1H); Anal. Calcd for C12H11N2O5B•1/4H2O (C, H, N) (51.74, 4.16, 10.06). Found (51.98, 4.13,
9.58); HRMS calcd for C12H12N2O5B [M+H] 275.0834, found 275.0836 (Δ 0.24).
Furo[3,2-c]-2-boronic acid (13): Prepared from 4-hydroxy-3-iodopyridine and ethynylboronic acid
MIDA ester. The resulting mixture was diluted with water and extracted with AcOEt. The organic layers
were dried over Na2SO4 and concentrated. The residue was purified by flash chromatography (SiO2,
CH2Cl2 : MeOH = 10 : 1) to give 180.7 mg of 1 : 1 mixture of MIDA boronate and boronic acid as a pale
yellow powder (41%). The mixture was treated with hot EtOH to afford 13 (109.9 mg, 34%) as a pale
yellow solid; IR (cm-1) 3000, 1736, 1616, 1591, 1570, 1541, 1473, 1373, 1356, 1300, 1228, 1164, 1145,
1039; 1H-NMR (DMSO-d6) δ 7.57 (d, J = 0.5 Hz, 1H), 7.65 (d, J = 6.0 Hz, 1H), 8.46 (d, J = 6.0 Hz, 1H),
9.00 (s, 1H); HRMS calcd for C7H7NO3B [M+H] 164.0514, found 164.0513 (Δ 0.05).
Furo[2,3-c]-2-boronic acid (14): Prepared from 3-hydroxy-4-iodopyridine and ethynylboronic acid
MIDA ester. The resulting mixture was diluted with water and extracted with AcOEt. The organic layers
were dried over Na2SO4 and concentrated. The residue was purified by flash chromatography (SiO2,
CH2Cl2 : MeOH = 10 : 1) to give 262.4 mg of 1 : 1 mixture of MIDA boronate and boronic acid as a pale
yellow powder. The mixture was treated with hot EtOH to afford 14 (216.4 mg, 66%) as a pale yellow
1
solid; IR (cm-1) 3006, 1734, 1683, 1608, 1473, 1373, 1322, 1259, 1216, 1159, 1093, 1016; H-NMR
(DMSO-d6) δ 7.50 (d, J = 1.0 Hz, 1H), 7.74 (dd, J = 1.0 Hz, 5.0 Hz, 1H), 8.37 (d, J = 5.0 Hz, 1H), 8.96
(brs, 1H); HRMS calcd for C7H7NO3B [M+H] 164.0514, found 164.0514 (Δ 0.07).
2-Phenylfuro[2,3-b]pyridine (15) via furo[2,3-b]pyridine-2-MIDA boronate: Prepared from
2-hydroxy-3-iodopyridine and ethynylboronic acid MIDA ester. The resulting mixture was diluted with
water and extracted with AcOEt. The organic layers were dried over Na2SO4 and concentrated. The
residue was purified by flash chromatography (SiO2, AcOEt) to give 386.0 mg of a pale yellow
amorphous solid. The crude product was used in the next reaction without further purification since the
product was unstable to EtOH treatment. 1H-NMR (crude, DMSO-d6) δ 2.73 (s, 3H), 4.21 (d, J = 17.0 Hz,
2H), 4.44 (d, J = 17.0 Hz, 2H), 7.14 (s, 1H), 7.33 (dd, J = 5.0 Hz, 7.5 Hz, 1H), 8.12 (dd, J = 1.5 Hz, 7.5
Hz, 1H), 8.30 (dd, J = 1.5 Hz, 5.0 Hz, 1H).
2 wt% DL-α-Tocopherolmethoxypolyeneglycol succinate solution (3.5 mL) was added to a mixture of the
crude furo[2,3-b]pyridine-2-MIDA boronate and bromobenzene (221 mg) under N2. Et3N (0.52 mL) was
added to the suspension under N2. The reaction mixture was vigorously stirred at 40 °C for 22 h under N2.
The resulting mixture was diluted with water and extracted with AcOEt. The organic layers were dried
over Na2SO4 and concentrated. The residue was purified by flash chromatography (SiO2, AcOEt : hexane
= 30 : 70) to give 15 (132.6 mg, 34%, 2 steps) as a yellow solid; mp 90-91 °C (hexane, yellow prisms); IR

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1
(cm-1) 1739, 1597, 1562, 1491, 1471, 1446, 1402, 1244, 1173, 1113, 1020; H-NMR (CDCl3) δ 7.01 (s,
1H), 7.23 (dd, J = 5.0 Hz, 7.5 Hz, 1H), 7.37-7.42 (m, 1H), 7.44-7.50 (m, 2H), 7.88-7.94 (m, 3H), 8.30 (dd,
J = 1.5 Hz, 5.0 Hz, 1H); Anal. Calcd for C13H9NO (C, H, N) (79.98, 4.65, 7.17). Found (80.50, 4.48,
7.23); HRMS calcd for C13H10NO [M+H] 196.0757, found 196.0757 (Δ 0.07).
5-Nitro-2-(thiazol-4-yl)furo[2,3-b]pyridine (16) via 5-nitrofuro[2,3-b]pyridine-2-2-MIDA boronate:
Prepared from 2-hydroxy-3-iodo-5-nitropyridine and ethynylboronic acid MIDA ester. The resulting
mixture was diluted with water and extracted with AcOEt. The organic layers were dried over Na2SO4
and concentrated. The residue was purified by flash chromatography (SiO2, AcOEt) to give 212.7 mg of a
pale brown amorphous solid. The crude product was used in the next reaction without further purification.
2 wt% DL-α-Tocopherolmethoxypolyeneglycol succinate solution (3.5 mL) was added to a mixture of the
crude furo[2,3-b]pyridine-2-MIDA boronate, (dtbpf)PdCl2 (104 mg) and 4-bromothiazole (0.33 g) under
N2. Et3N (0.61 mL) was added to the suspension under N2. The reaction mixture was vigorously stirred at
40 °C for 22 h under N2. The resulting mixture was diluted with water and extracted with AcOEt. The
organic layers were dried over Na2SO4 and concentrated. The residue was purified by flash
chromatography (SiO2, AcOEt : hexane = 30 : 70) to give 16 (34.5 mg, 7%, 2 steps) as a yellow solid; mp
273-276 °C (Dec., AcOEt-hexane, yellow powder); IR (cm-1) 1738, 1604, 1508, 1471, 1348, 1265, 1155,
1076, 1041; 1H-NMR (CDCl3) δ 7.37 (s, 1H), 8.01 (d, J = 2.0 Hz, 1H), 8.79 (d, J = 2.5 Hz, 1H), 8.95 (d, J
= 2.0 Hz, 1H), 9.24 (d, J = 2.5 Hz, 1H); HRMS calcd for C10H6N3O3S [M+H] 248.0124, found 248.0122
(Δ 0.23).
1-Ts-1H-indole-2-MIDA boronate (17): Prepared from 2-iodo-1-Ts-aniline and ethynylboronic acid
MIDA ester. Purification by flash chromatography (AcOEt) afforded 17 (693.2 mg, 81%) as a pale
1
yellow solid; IR (cm-1) 1747, 1446, 1362, 1300, 1228, 1173, 1090, 1036, 1011; H-NMR (DMSO-d6) δ
2.32 (s, 3H), 2.96 (s, 3H), 4.23 (d, J = 17.5 Hz, 2H), 4.47 (d, J = 17.5 Hz, 2H), 7.06 (d, J = 0.5 Hz, 1H),
7.22-7.28 (m, 1H), 7.33-7.41 (m, 3H), 7.63 (brd, J = 7.5 Hz, 1H), 7.91 (brd, J = 8.5 Hz, 2H), 8.10-8.13 (m,
1H); HRMS calcd for C20H20N2O6BS [M+H ] 427.1130, found 427.1130 (Δ 0.01).
2-Phenyl-1-Ns-1H-indole (18) via 1-Ns-1H-indole-2-MIDA boronate: Prepared from 2-iodo-1-Ns-
aniline and ethynylboronic acid MIDA ester. The resulting mixture was diluted with water to form a
precipitate, which was filtered, washed with water and dried at room temperature. The obtained solid was
dissolved in acetone and purified by flash chromatography (SiO2, AcOEt). The eluted material was
washed with hot EtOH and dried to give 572.4 mg of crude MIDA boronate as a pale brown solid. The
crude product was used in the next reaction without further purification. 2 wt% DL-α-Tocopherol-
methoxypolyeneglycol succinate solution (3.5 mL) was added to a mixture of the crude furo-
[2,3-b]pyridine-2-MIDA boronate, (dtbpf)PdCl2 (104 mg) and 4-bromothiazole (0.33 g) under N2. Et3N
(0.61 mL) was added to the suspension under N2. The reaction mixture was vigorously stirred at 40 °C for

HETEROCYCLES, Vol. 94, No. 7, 2017
1333
22 h under N2. The resulting mixture was diluted with water and extracted with AcOEt. The organic
layers were dried over Na2SO4 and concentrated. The residue was purified by flash chromatography (SiO2,
AcOEt : hexane = 30 : 70) to give 18 (246.7 mg, 15%, 2 steps) as a pale yellow solid; mp 100-102 °C
1
(hexane, pale yellow powder); IR (cm-1) 1739, 1541, 1448, 1362, 1215, 1174, 1119, 1059; H-NMR
(CDCl3) δ 6.64 (d, J = 0.5 Hz, 1H), 7.09 (dd, J = 1.0 Hz, 8.0 Hz, 1H), 7.26-7.40 (m, 8H), 7.55-7.64 (m,
3H), 8.06-8.10 (m, 1H); Anal. Calcd for C20H14N2O4S (C, H, N) (63.48, 3.78, 7.40). Found (63.35, 3.93,
7.28); HRMS calcd for C20H15N2O4S [M+H] 379.0747, found 379.0749 (Δ 0.25).
N-Boc-2-(ethynylboronic acid MIDA ester)aniline (19): Prepared from 2-iodo-N-Boc-aniline and
ethynylboronic acid MIDA ester. Purification by flash chromatography (AcOEt) afforded 19 (521.9 mg,
70%) as a pale yellow powder; mp 77-79 °C (hexane, pale yellow powder); IR (cm-1) 1766, 1734, 1577,
1516, 1446, 1367, 1230, 1149, 1117, 1065, 1020; 1H-NMR (DMSO-d6) δ 1.45 (s, 9H), 3.13 (s, 3H), 4.14
(d, J = 17.0 Hz, 2H), 4.33 (d, J = 17.0 Hz, 2H), 7.06-7.11 (m, 1H), 7.33-7.39 (m, 1H), 7.46 (dd, J = 1.5
Hz, 8.0 Hz, 1H), 7.66 (d, J = 8.0 Hz, 1H), 8.25 (s, 1H); C18H21N2O6BNa [M+Na] 395.13947, found
395.14924 (Δ 0.97).
5-Chloro-1-Ts-1H-indole-2-MIDA boronate (20): Prepared from 4-chloro-2-iodo-1-Ts-aniline and
ethynylboronic acid MIDA ester. Purification by flash chromatography (AcOEt) afforded 20 (637.9 mg,
69%) as a white solid; mp 170-174 °C (Dec.); IR (cm-1) 1743, 1522, 1446, 1363, 1296, 1228, 1171, 1090,
1
1039; H-NMR (DMSO-d6) δ 2.33 (s, 3H), 2.95 (s, 3H), 4.24 (d, J = 17.5 Hz, 2H), 4.47 (d, J = 17.5 Hz,
2H), 7.05 (brs, 1H), 7.36-7.42 (m, 3H), 7.75 (d, J = 2.0 Hz, 1H), 7.75 (d, J = 8.5 Hz, 2H), 8.13 (d, J = 9.0
Hz, 1H); Anal. Calcd for C20H18N2O6BClS•1/4H2O (C, H, N) (51.64, 4.01, 6.02). Found (51.80, 3.73,
5.74); HRMS calcd for C20H19N2O6BClS [M+H] 461.0740, found 461.0740 (Δ 0.04).
5-Methoxycarbonyl-1-Ts-1H-indole-2-MIDA boronate (21): Prepared from 4-methoxycarbonyl-2-
iodo-1-Ts-aniline and ethynylboronic acid MIDA ester. Purification by flash chromatography (AcOEt)
afforded 21 (592.8 mg, 61%) as a white solid; mp 246-250 °C (Dec.); IR (cm-1) 1743, 1716, 1369, 1369,
1230, 1171, 1136, 1090, 1031, 1003; 1H-NMR (DMSO-d6) δ 2.33 (s, 3H), 2.96 (s, 3H), 3.86 (s, 3H), 4.25
(d, J = 17.5 Hz, 2H), 4.48 (d, J = 17.5 Hz, 2H), 7.20 (d, J = 0.5 Hz, 1H), 7.40 (d, J = 8.0 Hz, 2H), 7.91-
7.98 (m, 3H), 8.25 (d, J = 9.0 Hz, 1H), 8.29 (d, J = 1.5 Hz, 1H); Anal. Calcd for C22H21N2O8BS•1/4H2O
(C, H, N) (54.06, 4.43, 5.73). Found (53.86, 4.05, 5.49); HRMS calcd for C20H22N2O8BS [M+H]
485.1184, found 485.1183 (Δ 0.19).
6-Methoxycarbonyl-1-Ts-1H-indole-2-MIDA boronate (22): Prepared from 5-methoxycarbonyl-
2-iodo-1-Ts-aniline and ethynylboronic acid MIDA ester. Purification by flash chromatography (AcOEt)
afforded 22 (820.7 mg, 85%) as a pale yellow, amorphous solid; IR (cm-1) 1739, 1716, 1558, 1541, 1456,
1419, 1373, 1228, 1205, 1091; 1H-NMR (DMSO-d6) δ 2.32 (s, 3H), 2.95 (s, 3H), 3.91 (s, 3H), 4.24 (d, J
= 17.5 Hz, 2H), 4.48 (d, J = 17.5 Hz, 2H), 7.16 (d, J = 0.5 Hz, 1H), 7.41 (d, J = 8.0 Hz, 2H), 7.75-7.79 (m,

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1H), 7.81-7.85 (m, 2H), 7.87 (dd, J = 1.5 Hz, 8.0 Hz, 1H), 8.77 (d, J = 0.5 Hz, 1H); HRMS calcd for
C22H22N2O8BS [M+H] 485.1184, found 485.1188 (Δ 0.48).
5-Trifloromethyl-1-Ts-1H-indole-2-MIDA boronate (23): Prepared from 4-trifluoromethyl-2-iodo-
1-Ts-aniline and ethynylboronic acid MIDA ester. Purification by flash chromatography (AcOEt) and
recrystallization from EtOH afforded 23 (495.1 mg, 50%) as a white solid; mp 221-224 °C (Dec.);
1H-NMR (DMSO-d6) δ 2.33 (s, 3H), 2.95 (s, 3H), 4.25 (d, J = 17.5 Hz, 2H), 4.49 (d, J = 17.5 Hz, 2H),
7.20 (s, 1H), 7.41 (brd, J = 8.0 Hz, 2H), 7.69 (dd, J = 1.5 Hz, 9.0 Hz, 1H), 7.94 (brd, J = 8.5 Hz, 2H),
8.09-8.12 (m, 1H), 8.33 (d, J = 9.0 Hz, 1H); Anal. Calcd for C21H18BF3N2O6S (C, H, N) (51.03, 3.67,
5.67). Found (50.69, 3.42, 5.55); HRMS calcd for C21H19O6N2BF3S [M+H] 495.1003, found 495.1003 (Δ
0.07).
5-Methoxy-1-Ts-1H-indole-2-MIDA boronate (24): Prepared from 4-methoxy-2-iodo-1-Ts-aniline and
ethynylboronic acid MIDA ester. Purification by flash chromatography (AcOEt) and recrystallization
from EtOH afforded 24 (409.3 mg, 45%) as a pale yellow solid; mp 184-187 °C; IR (cm-1) 1739, 1527,
1456, 1363, 1338, 1298, 1203, 1169, 1088, 1032; 1H-NMR (DMSO-d6) δ 2.31 (s, 3H), 2.95 (s, 3H), 3.75
(s, 3H), 4.22 (d, J = 17.5 Hz, 2H), 4.46 (d, J = 17.5 Hz, 2H), 6.94-6.99 (m, 2H), 7.14 (d, J = 2.5 Hz, 1H),
7.37 (brd, J = 8.0 Hz, 2H), 7.86 (brd, J = 8.5 Hz, 2H), 8.00 (d, J = 9.0 Hz, 1H); Anal. Calcd for
C21H21N2O7BS•1/8H2O (C, H, N) (55.00, 4.67, 6.10). Found (54.79, 4.34, 5.94); HRMS calcd for
C21H22N2O7BS [M+H] 457.1235, found 457.1540 (Δ 0.59).
5-Methoxy-1-Ns-1H-indole-2-MIDA boronate (25): Prepared from 4-methoxy-2-iodo-1-Ns-aniline and
ethynylboronic acid MIDA ester. Purification by flash chromatography (AcOEt) and trituration with hot
EtOH afforded 25 (392.1 mg, 40%) as a pale brown solid; mp 250-253 °C (Dec.); IR (cm-1) 1749, 1541,
1458, 1365, 1300, 1200, 1171, 1038, 1012; 1H-NMR (DMSO-d6) δ 2.91 (s, 3H), 3.79 (s, 3H), 4.16 (d, J =
17.5 Hz, 2H), 4.37 (d, J = 17.5 Hz, 2H), 6.54 (dd, J = 1.0 Hz, 8.0 Hz, 1H), 6.97 (dd, J = 2.5 Hz, 9.5 Hz,
1H), 7.14 (d, J = 0.5 Hz, 1H), 7.29 (d, J = 2.5 Hz, 1H), 7.72 (dd, J = 1.0 Hz, 7.5 Hz, 1H), 7.76 (d, J = 9.5
Hz, 1H), 7.88 (ddd, J = 1.0 Hz, 7.5 Hz, 7.5 Hz, 1H), 8.21 (dd, J = 1.0 Hz, 8.0 Hz, 1H); Anal. Calcd for
C20H18N3O9BS•1/4H2O (C, H, N) (48.85, 3.79, 8.54). Found (48.85, 3.65, 8.23); HRMS calcd for
C20H19N3O9BS [M+H] 488.0930, found 488.0935 (Δ 0.55).
1-Ts-1H-pyrrolo[2,3-b]pyridine-2-MIDA boronate (26): Prepared from 3-iodo-2-N-Ts-aminopyridine
and ethynylboronic acid MIDA ester. Purification by flash chromatography (AcOEt) and trituration with
hot EtOH afforded 26 (476.1 mg, 56%) as a pale yellow solid; mp 166-170 °C; IR (cm-1) 1743, 1363,
1340, 1306, 1250, 1176, 1090, 1032, 1009; 1H-NMR (DMSO-d6) δ 2.35 (s, 3H), 3.06 (s, 3H), 4.28 (d, J =
17.5 Hz, 2H), 4.50 (d, J = 17.5 Hz, 2H), 7.03 (s, 1H), 7.30 (dd, J = 4.5 Hz, 8.0 Hz, 1H), 7.43 (brd, J = 8.5
Hz, 2H), 8.05 (dd, J = 1.5 Hz, 8.0 Hz, 1H), 8.15 (brd, J = 8.5 Hz, 2H), 8.41 (dd, J = 1.5 Hz, 4.5 Hz, 1H);
Anal. Calcd for C19H18N3O6BS•1/4H2O (C, H, N) (52.86, 4.32, 9.73). Found (52.70, 4.28, 9.58); HRMS

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calcd for C19H19N3O6BS [M+H] 428.1087, found 428.1091 (Δ 0.46).
1-Ts-1H-pyrrolo[2,3-c]pyridine-2-MIDA boronate (27): Prepared from 4-iodo-3-N-Ts-aminopyridine
and ethynylboronic acid MIDA ester. Purification by flash chromatography (AcOEt) and trituration with
1
hot EtOH afforded 27 (395.3 mg, 46%) as a pale yellow solid; mp 216-220 °C (Dec.), H-NMR
(DMSO-d6) δ 2.33 (s, 3H), 2.95 (s, 3H), 4.26 (d, J = 17.5 Hz, 2H), 4.50 (d, J = 17.5 Hz, 2H), 7.10 (d, J =
0.5 Hz, 1H), 7.42 (d, J = 8.0 Hz, 2H), 7.67 (dd, J = 1.0 Hz, 5.0 Hz, 1H), 7.98 (d, J = 8.5 Hz, 2H), 7.88 (d,
J = 5.0 Hz, 1H), 9.38 (s, 1H); Anal. Calcd for C19H18N3O6BS (C, H, N) (53.41, 4.25, 9.84). Found (53.52,
3.99, 9.32); HRMS calcd for C19H19N3O8BS [M+H] 428.1082, found 428.1084 (Δ 0.22).
1-Ns-1H-pyrrolo[2,3-c]pyridine-2-MIDA boronate (28): Prepared from 4-iodo-3-N-Ns-aminopyridine
and ethynylboronic acid MIDA ester. Purification by flash chromatography (AcOEt) and trituration with
hot EtOH afforded 28 (139.1 mg, 15%) as a pale yellow solid; mp 262-264 °C (Dec.); IR (cm-1) 1757,
1537, 1427, 1369, 1357, 1292, 1227, 1217, 1182, 1171, 1147, 1070, 1011; 1H-NMR (DMSO-d6) δ 2.89 (s,
3H), 4.17 (d, J = 17.5 Hz, 2H), 4.38 (d, J = 17.5 Hz, 2H), 6.65 (dd, J = 1.0 Hz, 8.0 Hz, 1H), 7.26 (s, 1H),
(d, J = 1.5 Hz, 1H), 7.76 (ddd, J = 1.0 Hz, 8.0 Hz, 8.0 Hz, 1H), 7.82 (dd, J = 1.0 Hz, 5.0 Hz, 1H), 7.93
(ddd, J = 1.0 Hz, 8.0 Hz, 8.0 Hz, 1H), 8.27 (dd, J = 1.0 Hz, 8.0 Hz, 1H), 8.48 (d, J = 5.0 Hz, 1H), 9.19 (s,
1H); Anal. Calcd for C18H15N4O8BS (C, H, N) (47.18, 3.30, 12.23). Found (46.87, 3.27, 12.16); HRMS
calcd for C18H16N4O8BS [M+H] 459.0776, found 459.0776 (Δ 0.004).
General procedure for the preparation of 2-aryl product. 5-Methoxycarbonyl-2-phenylbenzofuran:
2 wt% DL-α-Tocopherolmethoxypolyeneglycol succinate solution (1.5 mL) was added to a mixture of
5-methoxycarbonylbenzofuran-2-MIDA boronate (200 mg, 0.604 mmol), (dtbpf)PdCl2 (32 mg, 0.048
mmol) and bromobenzene (95 mg, 0.604 mmol) under N2. Et3N (0.25 mL, 1.81 mmol) was added to the
suspension under N2. The reaction mixture was vigorously stirred at 40 °C for 22 h under N2. The
resulting mixture was diluted with water to form a precipitate, which was filtered, washed with water and
dissolved with CHCl3. The obtained organic solutions were dried over Na2SO4 and concentrated. The
residue was purified by flash chromatography (SiO2, AcOEt : hexane = 30 : 70) to give 143.0 mg (94%)
of white powder; mp 155-157 °C (EtOH, white powder); IR (cm-1) 1739, 1716, 1435, 1373, 1306, 1230,
1
1157, 1114, 1806, 1036, 1018; H-NMR (CDCl3) δ 3.95 (s, 3H), 7.08 (d, J = 1.0 Hz, 1H), 7.36-7.41 (m,
1H), 7.44-7.50 (m, 2H), 7.55 (d, J = 8.5 Hz, 1H), 7.85-7.90 (m, 2H), 8.02 (dd, J = 1.5 Hz, 8.5 Hz, 1H),
8.32 (d, J = 1.5 Hz, 1H); Anal. Calcd for C16H12O3 (C, H, N) (76.18, 4.79, 0.00). Found (76.15, 4.65,
0.00); HRMS calcd for C16H13O3 [M+H] 253.0859, found 253.0859 (Δ 0.03).
ACKNOWLEDGEMENTS
I wish to thank Mr. Masakazu Nagasawa of this company for obtaining the high-resolution MS spectral
data.

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