Functionalization of organotrifluoroborates via CU-catalyzed C-N coupling reaction

Article abstract of DOI:10.5012/bkcs.2013.34.1.42

Potassium N-heterobiaryltrifluoroborates were successfully prepared via a selective Cu-catalyzed C-N coupling reaction. The BF3K moiety was well tolerated under the reaction conditions involving CuI and dimethylethylenediamine (DMEDA) in the presence of DMSO. The Pd-catalyzed Suzuki-Miyaura cross couplings of potassium N-heterobiaryltrifluoroborates with bromoarenes were studied to prepare the N-heterotriaryl compounds. Moreover, homocoupling, iodination, and hydroxylation of potassium N-heterobiaryltrifluoroborates provided the corresponding products in high yields.

Full text of DOI:10.5012/bkcs.2013.34.1.42

42 Bull. Korean Chem. Soc. 2013, Vol. 34, No. 1
http://dx.doi.org/10.5012/bkcs.2013.34.1.42
Jung-Hyun Lee et al.
Functionalization of Organotrifluoroborates via Cu-Catalyzed C-N Coupling Reaction
a,†
Jung-Hyun Lee, Heejin Kim, Taejung Kim, Jung Ho Song, Won-Suk Kim, and Jungyeob Ham
a
†,*
*
MarineChemomics Laboratory, Natural Medicine Center, Korea Institute of Science and Technology,
*
Gangneung 210-340, Korea. E-mail: ham0606@kist.re.kr
†
Advanced Organic Synthesis Laboratory, Department of Chemistry and Nano Science, Ewha Womans University,
*
Seoul 120-750, Korea. E-mail: wonsukk@ewha.ac.kr
Received September 11, 2012, Accepted September 12, 2012
Potassium N-heterobiaryltrifluoroborates were successfully prepared via a selective Cu-catalyzed C-N coupl-
ing reaction. The BF3K moiety was well tolerated under the reaction conditions involving CuI and dimethyl-
ethylenediamine (DMEDA) in the presence of DMSO. The Pd-catalyzed Suzuki-Miyaura cross couplings of
potassium N-heterobiaryltrifluoroborates with bromoarenes were studied to prepare the N-heterotriaryl compounds.
Moreover, homocoupling, iodination, and hydroxylation of potassium N-heterobiaryltrifluoroborates provided
the corresponding products in high yields.
Key Words : Organotrifluoroborate, Potassium N-heterobiaryltrifluoroborates, Cu-catalyzed C-N coupling,
Chan-Lam coupling, N-Heterobiarene
Introduction
N-Heterobiarenes are ubiquitous in many bioactive natural
1
products, pharmaceutical drugs, and organic materials.
2
3
For example, Tepoxalin, a N-aryl pyrazole derivative, has
been reported as a novel dual inhibitor of COX (COX-1 and
4
COX-2) and LOX. DPC-423, developed by Bristol Myers
5
Squibb, shows antithrombotic effects in human plasma. The
parent compound of Meribendan, CI 930 inhibits the action
of the phosphodiesterase enzyme PDE3 (Scheme 1).
One of the most powerful synthetic methods to prepare N-
Scheme 2. Our synthetic route for the selective preparation of N-
heterobiaryltrifluoroborates.
7
heterobiarenes is the Cu-catalyzed C-N coupling reaction.
and co-workers reported that potassium aryltrifluoroborates
could be utilized in Cu(OAc)2-catalyzed C-N bond coupl-
A large number of this Ullmann-type coupling reaction with
various coupling partners (nucleophiles), including not only
arylhalides but also arylboronic acids and aryltrifluoro-
borates, have been reported. Particularly, Cu-catalyzed C-N
bond formation employing the arylboronic acids as a coupl-
ing partner are known as the Chan-Lam coupling and it has
8d
ing. However, to the best of our knowledge, there is no
reports on the preparation of the potassium N-heterobiaryl-
trifluoroborates by the selective Cu-catalyzed Ullmann-type
reaction with halobenzene derivatives bearing a BF3K moiety
on the phenyl ring.
8
been widely demonstrated by various research groups.
Over the last decade, organotrifluoroborate salts have
attracted a great deal of attention because of their excellent
air and moisture stability as well as their remarkable toler-
ance to harsh conditions in numerous synthetic reactions.
For instance, direct functionalizations of organotrifluoro-
Sreedhar and co-workers developed a Cu2O-catalyzed C-N
8c
cross-coupling of arylboronic acids with N-heteroarenes.
Surprisingly, bromophenylboronic acids and imidazole were
used as coupling partners, bromo-substituted N-hetero-
biarene was obtained as a major product. Moreover, Batey
9a 9b
borates via epoxidation, Jones oxidation, Wittig olefina-
9c
9d
9e
tion, click reaction or halogen-lithium exchange have
been successfully performed without elimination of the
BF3K group. In addition, numerous transformations of the
BF3K group in the reactions, such as Suzuki-Miyaura
10 11
coupling, halogenation, hydroxylation, and C-N bond
8d
formation have been investigated.
Developing a synthetic method employing various organo-
trifluoroborate, thus, would be important for expanding the
scope of organotrifluoroborate chemistry. In here, we report
the synthesis of potassium N-heterobiaryltrifluoroborates
using the selective Cu-catalyzed Ullmann-type condensation
Scheme 1. Selected examples of the biologically active N-hetero-
biarenes.
a
These authors contributed equally to this work.

Preparation of Potassium N-Heterobiaryltrifluoroborates
Bull. Korean Chem. Soc. 2013, Vol. 34, No. 1 43
of halophenyltrifluoroborates with N-heteroarenes (Scheme
catalyzed coupling reaction (Table 2). In most cases, the
2).
desired potassium N-heterobiaryltrifluoroborates were obtain-
Results and Discussion
Table 2. Preparation of N-heterobiaryltrifluoroborates via Cu-
a
catalyzed C-N coupling reaction
We first focused on the synthesis of potassium 4-(1H-
pyrazolyl)phenyltrifluoroborate (1a) employing potassium
12
4-iodoaryltrifluoroborate with pyrazole (Table 1).
13
In our previous study, we found that Cu-catalyzed
azidation of potassium 4-haloaryltrifluoroborates could be
effective without loss of the BF3K moiety. N,N'-Dimethyl-
ethylenediamine (DMEDA) was the best ligand among all
the amine ligands tested, and it provided the highest conver-
sion yield in shortest time. Thus, DMEDA was chosen as the
ligand in the present study and the reaction was carried out
in DMSO-d6 in an NMR tube. The reaction was monitored
b
Entry N-Heteroarene Time (h)
Product
Yield (%)
1
by H NMR. Various catalysts, including Cu(I) and Cu(II)
salts were screened for the C-N bond formation (Table 1,
entries 1-6). The reactions were carried out in the presence
of Cu (II) catalyst such as Cu(acac)2 and Cu(OAc)2 (Table 1,
entries 1 and 2). However, the reactions did not complete
even after heating at 120 °C for 4 h. In contrast, the reaction
proceeded at a faster rate in the presence of CuBr or CuO2,
and full conversion was observed within 4 h. Nevertheless,
the best catalyst was CuI as it afforded the product in
excellent isolated yield (Table 1, entry 6) in 2 h. Test reac-
tions using a variety of bases (cf. Cs2CO3, K3PO4, K2CO3,
NaOtBu, and KOtBu) indicated Cs2CO3 to be the best (Table
1, entries 6-10). The reaction rate decreased considerably
when the reaction temperature was lowered to 100 °C (Table
1, entry 11).
We applied these optimized conditions to various nitrogen-
containing heteroarenes to explore the scope of the CuI-
Table 1. Preparation of the preparation potassium 4-(1H-pyrazol-
a
yl)phenyltrifluoroborate (1a)
b
Entry
Catalyst
Base
Time (h) Conversion yield (%)
1
2
Cu(acac)2 Cs2CO3
Cu(OAc)2 Cs2CO3
CuBrSMe2 Cs2CO3
4
4
4
79
81
3
64
c
c
c
4
CuBr
Cu2O
CuI
CuI
Cs2CO3
Cs2CO3
Cs2CO3
K3PO4
100 (93)
100 (98)
100 (98)
80
5
4
2
4
4
4
4
9
6
7
8
CuI
K2CO3
47
t
NaO Bu
9
CuI
54
t
KO Bu
10
CuI
< 5
d
11
CuI
Cs2CO3
70
a
All reactions were performed with 0.1 mmol of potassium 4-iodo-
phenyltrifluoroborate and 1.1 equiv of pyrazole in 0.5 mL of DMSO-d6.
b
1
The conversion yield was based on the integration of H NMR peaks at
8.35 ppm (potassium 4-iodophenyltrifluoroborate) and 7.15 ppm (1a),
c d
respectively. Isolated yields. Reaction temperature was 100 °C.

44 Bull. Korean Chem. Soc. 2013, Vol. 34, No. 1
Table 2. (continued)
Jung-Hyun Lee et al.
b
Entry N-Heteroarene Time (h)
Product
Yield (%)
Scheme 3. Various functionalization of potassium 4-(1H-pyrazol-
yl)phenyltrifluoroborate (1a).
a
All reactions were performed with a 0.5 mmol of potassium iodophenyl-
b
trifluoroborate and 1.1 equiv of pyrazole in 2 mL of DMSO. Isolated
c
yields. Reaction temperature was 130 °C.
1c in 40% yield, probably due to the steric effect (Table 2,
entry 3). Two regioisomers, 1e and 1f were obtained when 3-
methylpyrazole was used as the coupling partner due to the
electron-donating effect of the methyl group (Table 2, entry
Table 3. Suzuki-Miyaura cross-coupling of potassium pyrazolyl-
a
phenyltrifluoroborates with bromoarenes
14
5). Moreover, the regioisomers (1g/1h, 1l/1m, and 1n/1o)
were obtained in a ratio of 2:1 to 8:1 when 1,2,3-triazole,
indazole, and benzotriazole were used as the coupling
partners (Table 2, entries 6, 10 and 11).
b
Entry
ArBr
Time (min)
Product
Yield (%)
N-arylpyrazoles are well known core framework in drug
2 15
development. For example, Rimonabant, an anorectic anti-
16
obesity drug, and Celecoxib, a sulfa-NSAID, commonly
contain the N-arylpyrazole skeleton. In our ongoing project,
we also studied on the synthesis of biologically active
compound libraries including the N-arylpyrazole core. We
were interested in the functionalization of N-arylpyrazole
compounds bearing a BF3K moiety by Suzuki-Miyaura cross
coupling with bromoarenes. Under the optimized conditions
17
that we developed, we conducted the cross coupling reac-
tion of potassium 4- or 3-(1H-pyrazolyl)-phenyltrifluorobo-
rate (1a or 1b) with bromoarenes bearing various functional
groups. As illustrated in Table 3, all the reactions proceeded
to 100% completion within 1 h to afford the desired N-
heterotriaryl compounds in good to excellent yields.
Finally, we further attempted functionalization reactions
of 1a towards homocoupling, iodination, and hydroxylation.
The results are summarized in Scheme 3. Homocoupling of
1a under the same conditions used for cross coupling with-
out bromoarenes afforded the desired homocoupled product
10
3 in 90% yield. Iodination of the BF3K group of 1a was
also successfully accomplished to give the product 4 in 90%
11
yield. Furthermore, hydroxylation of 1a using oxone gave
the corresponding phenol derivative 5 in high yield.
Conclusion
a
All reactions were performed with a 0.3 mmol of 4-(1H-pyrazol-1-
In summary, Cu-catalyzed functionalization of potassium
iodoaryltrifluoroborates with N-heteroarenes was success-
fully accomplished without loss of the BF3K moiety. The
intact BF3K moiety could be further utilized in Suzuki-
Miyaura cross coupling to afford N-heterotriaryl compounds.
yl)phenyltrifluoroborate (0.3 mmol) and 1.1 equiv of arylbromide in 2
b
mL of MeOH. Isolated yield.
ed in good to excellent yields. However, coupling of 2-
iodoaryltrifluoroborate and pyrazole furnished the product

Preparation of Potassium N-Heterobiaryltrifluoroborates
Bull. Korean Chem. Soc. 2013, Vol. 34, No. 1 45
+ −
[M-K ] 211.07, found 211.04.
Moreover, homocoupling, iodination, and hydroxylation were
investigated. Further applications and developments based
on this methodology are currently under investigation.
Potassium 2-(1H-pyrazol-1-yl)phenyltrifluoroborate
o
1
(1c). Brown solid; mp 250 C; H NMR (400 MHz, acetone-
d6) δ 8.49 (s, 1H), 7.74 (d, 1H, J = 6.8 Hz), 7.51 (s, 1H), 7.48
(d, 1H, J = 7.6 Hz), 7.18 (t, 1H, J = 14.8 Hz), 7.12 (t, 1H, J =
Experimental Section
13
14.0 Hz), 6.26 (s, 1H); C NMR (100 MHz, acetone-d6) δ
1
General Information. H, C, and F NMR spectra were
13
19
19
145.2, 139.4, 135.2, 132.6, 127.0, 126.1, 124.5, 105.3; F
19
recorded at 400, 100, and 376 MHz, respectively. F NMR
11
NMR (376 MHz, acetone-d6) δ −135.9; B NMR (128
MHz, acetone-d6) δ 3.02; FT-IR (ATR): 3444, 2925, 2854,
chemical shifts were referenced to external CFCl3 (0.0 ppm).
11
−1
2359, 2341, 1588, 1519, 1456, 1402, 1123, 1083, 756 cm ;
B NMR spectra at 128 MHz were obtained on a spectro-
+ −
ESIMS: m/z calcd for C13H15BF3O2 [M-K ] 211.07, found
meter equipped with the appropriate decoupling accessories.
11
All B NMR chemical shifts were referenced to external
211.03.
BF3·OEt2 (0.0 ppm) with a negative sign indicating an up-
field shift. Mass spectra of potassium 1,2,3-triazoletrifluoro-
borates were recorded on LCQ Fleet Ion Trap Mass Spectro-
meter (ESI-MS) using negative ESI mode at the mass
spectrometry facilities in KIST-Gangneung Institute. IR
spectra were obtained using Nicolet iS10 FT-IR spectro-
meter. Melting points were performed on recrystallized
solids and recorded on Stanford Research Systems OptiMelt
MPA100 melting point apparatus and are uncorrected. Com-
mercially available reagents were used without purification
unless noted otherwise.
Potassium 4-(1H-pyrazol-1-yl)phenyltrifluoroborate
o 1
(1d). Brown solid; mp 208.7 C; H NMR (400 MHz,
acetone-d6) δ 7.56 (d, 2H, J = 8.0 Hz), 7.25 (d, 2H, J = 7.6
13
Hz), 7.17 (s, 2H), 6.22 (s, 2H); C NMR (100 MHz, acetone-
19
d6) δ 139.0, 133.7, 119.8, 119.0, 110.3; F NMR (376 MHz,
11
acetone-d6) δ −140.5; B NMR (128 MHz, acetone-d6) δ
3.46. FT-IR (ATR): 1604, 1520, 1476, 1401, 1328, 1216,
−1
1123, 960, 918, 823, 719 cm ; ESIMS: m/z calcd for
+ −
C13H15BF3O2 [M-K ] 210.07, found 211.01.
Potassium 4-(3-Methyl-1H-pyrazol-1-yl)phenyltrifluoro-
borate (1e) and Potassium 4-(5-Methyl-1H-pyrazol-1-
o
yl)phenyl-trifluoroborate (1f). White solid; mp 250 C; 1e:
General Procedure I (Preparation of Potassium N-
Heterobiaryltrifluoroborate, Table 2). To a solution of
potassium iodophenyltrifluoroborate (0.5 mmol), CuI (10
mol %), DMEDA (20 mol %), and Cs2CO3 (0.5 mmol) in
DMSO (2 mL) was added corresponding N-heteroarenes
(0.55 mmol) under atmospheric conditions. The reaction
1
H NMR (400 MHz, acetone-d6) δ 8.08 (s, 1H), 7.54 (d, 2H,
J = 12.8 Hz), 7.52 (d, 2H, J = 13.2 Hz), 6.22 (s, 1H), 2.27 (s,
1
3H); 1f: H NMR (400 MHz, acetone-d6) δ 7.59 (d, 2H, J =
7.6 Hz), 7.43 (s, 1H), 7.21 (d, 2H, J = 7.6 Hz), 6.17 (s, 1H),
19
2.31 (s, 3H); F NMR (376 MHz, acetone-d6) δ −140.18;
o
mixture was stirred in an oil bath at 120 C. After comple-
11
B NMR (128 MHz, acetone-d6) δ 3.31; FT-IR (ATR):
tion of the reaction, the solvent was removed in vacuo at 60-
2925, 1606, 1533, 1445, 1411, 1365, 1217, 966, 946, 826,
o
70 C. The residual product was dissolved in dry acetone (3
−1
+ −
747 cm ; ESIMS: m/z calcd for C13H15BF3O2 [M-K ]
225.08, found 225.00; The 5:1 ratio of 1e and 1f was based
on the integration of peaks at 6.22 (1e) and 6.17 (1f) ppm,
respectively.
mL), and the insoluble salts were removed by filtration
through Celite. The solvent was concentrated on a rotary
evaporator. The addition of Et2O led to the precipitation of
the product. The product was filtered and dried in vacuo to
afford the desired product.
Potassium 4-(2H-1,2,3-Triazol-2-yl)phenyltrifluorobo-
rate (1g) and Potassium 4-(1H-1,2,3-triazol-1-yl)phenyl-
o 1
trifluoro-borate (1h). White solid; mp 206.2 C; 1g: H
Potassium 4-(1H-pyrazol-1-yl)phenyltrifluoroborate
o
1
(1a). White solid; mp 250 C; H NMR (400 MHz, acetone-
d6) δ 8.19 (d, 1H, J = 2.4 Hz), 7.61 (d, 1H, J = 1.2 Hz), 7.58
(d, 2H, J = 10.4 Hz), 7.56 (d, 2H, J = 10.4 Hz), 6.44 (t, 1H, J
NMR (400 MHz, acetone-d6) δ 7.90 (s, 2H), 7.83 (d, 2H, J =
1
7.6 Hz), 7.66-7.61 (m, 2H); 1h: H NMR (400 MHz, acetone-
19
d6) δ 8.49 (s, 1H), 7.84 (s, 1H), 7.66-7.61 (m, 4H); F NMR
13
= 4.0 Hz); C NMR (100 MHz, acetone-d6) δ 140.6(C2),
11
(376 MHz, acetone-d6) δ −140.9; B NMR (128 MHz,
19
133.3, 127.3, 117.8, 107.4; F NMR (376 MHz, acetone-d6)
acetone-d6) δ 3.23; FT-IR (ATR): 3136, 2926, 1706, 1601,
11
δ −141.4; B NMR (128 MHz, acetone-d6) δ 3.72. FT-IR
−1
1511, 1411, 1379, 1219, 961, 945, 829 cm ; ESIMS: m/z
+ −
calcd for C13H15BF3O2 [M-K ] 212.06, found 212.02; The
(ATR): 1603, 1524, 1431, 1396, 1331, 1221, 1118, 1019, 966,
−1
933, 825, 741 cm ; ESIMS: m/z calcd for C13H15BF3O2
4:1 ratio of 1g and 1h was based on the integration of peaks
at 7.89 (1g) and 8.49 (1h) ppm, respectively.
+ −
[M-K ] 211.07, found 211.01.
Potassium 3-(1H-pyrazol-1-yl)phenyltrifluoroborate
Potassium 4-(1H-1,2,4-Triazol-1-yl)phenyltrifluorobo-
o
1
o 1
rate (1i). White solid; mp 250 C; H NMR (400 MHz,
(1b). Brown solid; mp 250 C; H NMR (400 MHz, acetone-
d6) δ 8.19 (d, 1H, J = 2.4 Hz), 7.85 (s, 1H), 7.62 (d, 1H, J =
1.2 Hz), 7.52 (d, 1H, J = 8.0 Hz), 7.43 (d, 1H, J = 7.2 Hz),
acetone-d6) δ 8.96 (s, 1H), 8.05 (s, 1H), 7.63 (d, 2H, J = 8.0
13
Hz), 7.58 (d, 2H, J = 8.0 Hz); C NMR (100 MHz, acetone-
13
7.22 (t, 1H, J = 15.2 Hz), 6.44 (t, 1H, J = 4.0 Hz); C NMR
19
d6) δ 152.8, 142.2, 135.8, 133.6, 118.6; F NMR (376 MHz,
11
acetone-d6) δ −140.6; B NMR (128 MHz, acetone-d6) δ
(100 MHz, acetone-d6) δ 140.7(C2), 130.9, 128.0, 127.6,
19
122.9, 117.0, 107.5; F NMR (376 MHz, acetone-d6) δ
3.38; FT-IR (ATR): 3122, 3039, 1603, 1522, 1207, 951, 877,
11
−140.7; B NMR (128 MHz, acetone-d6) δ 3.22. FT-IR
−1
820, 675, 652 cm ; ESIMS: m/z calcd for C13H15BF3O2 [M-
+ −
K ] 212.06, found 212.09.
(ATR): 2927, 2854, 1581, 1518, 1460, 1404, 1330, 1198,
−1
1050, 1026, 985 cm ; ESIMS: m/z calcd for C13H15BF3O2
Potassium 4-(1H-Indol-1-yl)phenyltrifluoroborate (1j).

46 Bull. Korean Chem. Soc. 2013, Vol. 34, No. 1
Jung-Hyun Lee et al.
o
1
Brown solid; mp 250 C; H NMR (400 MHz, acetone-d6) δ
7.68 (d, 2H, J = 7.6 Hz), 7.64 (d, 1H, J = 8.0 Hz), 7.55 (d,
1H, J = 8.0 Hz), 7.47 (d, 1H, J = 2.8 Hz), 7.30 (d, 2H, J = 7.6
Hz), 7.17 (t, 1H, J = 15.2 Hz), 7.09 (t, 1H, J = 14.8 Hz), 6.64
7.73 (d, 2H, J = 8.0 Hz), 7.52-7.50 (m, 1H), 7.35 (d, 2H, J =
13
8.0 Hz), 7.31-7.25 (m, 2H), 3.89 (s, 3H); C NMR (100
MHz, acetone-d6) δ 165.6, 137.9, 136.4, 135.3, 133.9, 127.9,
19
124.0, 123.6, 122.9, 122.2, 112.3, 108.7, 51.2; F NMR
13
(d, 1H, J = 2.8 Hz); C NMR (100 MHz, acetone-d6) δ
11
(376 MHz, acetone-d6) δ −141.12; B NMR (128 MHz,
137.8, 136.9, 133.7, 130.2, 129.3, 123.1, 122.7, 121.7,
acetone-d6) δ 3.49; FT-IR (ATR): 3036, 2947, 1687, 1601,
19
120.6, 111.4, 103.3; F NMR (376 MHz, acetone-d6) δ
−1
1533, 1456, 1202, 1111, 952, 832, 776, 746 cm ; ESIMS:
11
−142.1; B NMR (128 MHz, acetone-d6) δ 3.24; FT-IR
+ −
m/z calcd for C13H15BF3O2 [M-K ] 318.09, found 318.11.
(ATR): 3027, 2924, 1602, 1517, 1455, 1333, 1210, 949, 830,
General Procedure II (Suzuki-Miyaura Cross-Coupling
Reactions, Table 3). To a solution of potassium 4-(1H-
pyrazol-1-yl)phenyltrifluoroborate (0.3 mmol), Cs2CO3 (0.9
−1
738, 586 cm ; ESIMS: m/z calcd for C13H15BF3O2 [M-K ]
+ −
260.09, found 260.02.
−3
mmol), Pd(TPP)4 (5 × 10 mmol, 5 mol %) in methanol (2
Potassium 4-(1H-Pyrrolo[2,3-b]pyridin-1-yl)phenyl-
o
1
trifluoroborate (1k). White solid; mp 248.7 C; H NMR
(400 MHz, acetone-d6) δ 8.29 (d, 1H, J = 4.0 Hz), 8.03 (d,
1H, J = 7.6 Hz), 7.75 (d, 1H, J = 3.2 Hz), 7.65 (d, 2H, J = 8.0
Hz), 7.60 (d, 2H, J = 8.0 Hz), 7.14 (dd, 1H, J = 8.0 Hz, 4.8
mL) was added aryl bromide (0.33 mmol). The reaction was
o
conducted at 80 C. After the reaction was finished, water (5
mL) was added and organic layer was extracted with EtOAc
(5 mL × 3). The crude product was purified by column
chromatography to give pure product.
13
Hz), 6.65 (d, 1H, J = 3.6 Hz); C NMR (100 MHz, acetone-
d6) δ 148.5, 143.8, 136.9, 133.1, 129.5, 129.4, 122.8, 122.4,
1-(Biphenyl-4-yl)-1H-pyrazole (2a). White solid; mp
19
11
o
1
117.1, 101.6; F NMR (376 MHz, acetone-d6) δ −140.2; B
NMR (128 MHz, acetone-d6) δ 3.61; FT-IR (ATR): 3034,
1606, 1593, 1577, 1421, 1356, 1216, 958, 894, 830, 792,
124 C; H NMR (400 MHz, CDCl3) δ 7.99 (brs, 1H), 7.78
(d, 2H, J = 8.8 Hz), 7.77 (s, 1H), 7.68 (d, 2H, J = 8.4 Hz),
7.62 (d, 2H, J = 8.4 Hz), 7.46 (t, 2H, J = 7.6 Hz), 7.37 (t, 1H,
−1
771, 713 cm ; ESIMS: m/z calcd for C13H15BF3O2 [M-K ]
+ −
13
J = 7.4 Hz), 6.51 (brs, 1H); C NMR (126 MHz, CDCl3) δ
261.08, found 261.06.
141.2, 140.1, 139.4, 139.4, 128.9, 128.1, 127.5, 127.0,
127.0, 119.5, 107.7; FT-IR (ATR): 3130, 3107, 2923, 2853,
Potassium 4-(1H-Indazol-1-yl)phenyltrifluoroborate
(1l) and Potassium 4-(2H-indazol-2-yl)phenyltrifluoro-
−1
1607, 1528, 1484, 1393, 1332, 938, 834, 760, 698 cm ;
o
1
+
ESIMS: m/z calcd for C15H13N2 [M+H] 221.10, found
borate (1m). White solid; mp 250 C; 1l: H NMR (400
MHz, acetone-d6) δ 8.20 (s, 1H), 7.85-7.77 (m, 2H), 7.69 (d,
2H, J = 8.0 Hz), 7.50 (d, 2H, J = 7.6 Hz), 7.44 (t, 1H, J = 7.6
221.10.
1-(4'-Methylbiphenyl-4-yl)-1H-pyrazole (2b). White
1
Hz), 7.22 (t, 1H, J = 7.4 Hz); 1m: H NMR (400 MHz,
o
1
solid; mp 155 C; H NMR (400 MHz, CDCl3) δ 7.97 (s,
1H), 7.76 (d, 2H, J = 8.0 Hz), 7.75 (s, 1H), 7.67 (d, 2H, J =
8.4 Hz), 7.52 (d, 2H, J = 8.0 Hz), 7.27 (d, 2H, J = 8.0 Hz),
acetone-d6) δ 8.78 (s, 1H), 7.85 (d, 2H, J = 8.0 Hz), 7.85-
7.77 (m, 1H), 7.75 (d, 1H, J = 8.4 Hz), 7.67 (d, 2H, J = 8.0
19
F
13
6.50 (s, 1H), 2.41 (s, 3H); C NMR (100 MHz, CDCl3) δ
Hz), 7.28 (t, 1H, J = 8.0 Hz), 7.09 (t, 1H, J = 8.0 Hz);
11
NMR (376 MHz, acetone-d6) δ −141.3; B NMR (128 MHz,
acetone-d6) δ 3.49; FT-IR (ATR): 3062, 2926, 1605, 1515,
1464, 1422, 1379, 1223, 1199, 1023, 965, 905, 828, 737
141.2, 139.3, 139.2, 137.3, 129.6, 128.1, 127.8, 126.8,
126.5, 119.5, 107.7, 21.1; FT-IR (ATR): 3110, 3033, 2915,
−1
2856, 1610, 1515, 1497, 1393, 1050, 937, 805, 744 cm ;
−1
+ −
+
ESIMS: m/z calcd for C16H15N2 [M+H] 235.12, found
cm ; ESIMS: m/z calcd for C13H15BF3O2 [M-K ] 261.08,
found 261.05; The 2:1 ratio of 1l and 1m was based on the
integration of peaks at 8.20 (1l) and 8.77 (1m) ppm, respec-
tively.
235.10.
1-(4'-(Trifluoromethyl)biphenyl-4-yl)-1H-pyrazole (2c).
o 1
White solid; mp 189 C; H NMR (400 MHz, CDCl3) δ 7.99
Potassium 4-(1H-Benzo[d][1,2,3]triazol-1-yl)phenyl-tri-
fluoroborate (1n) and Potassium 4-(2H-benzo[d][1,2,3]-
triazol-2-yl)phenyltrifluoroborate (1o). White solid; mp
(s, 1H), 7.82 (d, 2H, J = 8.0 Hz), 7.76 (s, 1H), 7.69 (m, 6H),
13
6.51 (s, 1H); C NMR (100 MHz, CDCl3) δ 143.7, 141.6,
140.2, 137.9, 129.7 (q, J = 32.0 Hz), 128.4, 127.4, 126.9,
126.0 (q, J = 3.7 Hz), 124.4 (q, J = 270.0 Hz), 119.7. 108.1;
FT-IR (ATR): 3136, 2923, 1606, 1392, 1328, 1165, 1108,
o
1
162 C; 1n: H NMR (400 MHz, acetone-d6) δ 8.11 (d, 1H, J
= 8.4 Hz), 7.88 (d, 1H, J = 8.4 Hz), 7.79 (d, 2H, J = 8.4 Hz),
7.63 (t, 1H, J = 16.4 Hz), 7.58 (d, 2H, J = 7.6 Hz), 7.49 (t,
−1
1075, 1047, 935, 813, 753, 742, 669 cm ; ESIMS: m/z calcd
1
1H, J = 15.2 Hz); 1o: H NMR (400 MHz, acetone-d6) δ
+
for C16H12F3N2 [M+H] 289.09, found 289.10.
8.15 (d, 2H, J = 8.0 Hz), 7.97 (dd, 2H, J = 6.6, Hz, 3.2 Hz),
4'-(1H-Pyrazol-1-yl)biphenyl-4-carbonitrile (2d). White
19
7.73 (d, 2H, J = 8.4 Hz), 7.52-7.45 (m, 2H); F NMR (376
o
1
solid; mp 183 C; H NMR (400 MHz, CDCl3) δ 8.43 (d,
1H), 8.02 (d, 2H, J = 8.8 Hz), 7.95 (d, 2H, J = 8.4 Hz), 7.84
11
MHz, acetone-d6) δ −141.2; B NMR (128 MHz, acetone-
13
(m, 4H), 7.76 (s, 1H), 6.57 (t, 1H, J = 4.0 Hz); C NMR
d6) δ 3.41; FT-IR (ATR): 3031, 2928, 1601, 1502, 1452,
−1
1211, 1069, 1007, 953, 828, 784, 766, 742 cm ; ESIMS:
(100 MHz, CDCl3) δ 144.5, 141.6, 140.4, 137.1, 132.7,
128.3, 127.5, 126.8, 119.5, 118.9, 111.1, 108.2; FT-IR
(ATR): 3150, 3134, 3053, 2923, 2852, 2225, 1604, 1526,
+ −
m/z calcd for C13H15BF3O2 [M-K ] 262.08, found 262.09;
The 8:1 ratio of 1n and 1o was based on the integration of
peaks at 7.78 (1n) and 7.73 (1o) ppm, respectively.
−1
1493, 1435, 1388, 1333, 1034, 931, 818, 749, 736 cm ;
+
ESIMS: m/z calcd for C16H12N3 [M+H] 246.10, found
Potassium 4-(3-(Methoxycarbonyl)-1H-indol-1-yl)phen-
o 1
yl-trifluoroborate (1p). White solid; mp 154 C; H NMR
246.10.
(400 MHz, acetone-d6) δ 8.24-8.18 (m, 1H), 8.09 (s, 1H),
1-(3-(Benzo[d][1,3]dioxol-5-yl)phenyl)-1H-pyrazole (2e).

Preparation of Potassium N-Heterobiaryltrifluoroborates
Bull. Korean Chem. Soc. 2013, Vol. 34, No. 1 47
1
White solid; H NMR (400 MHz, CDCl3) δ 7.97 (s, 1H),
was stirred at rt for 5 min. The aqueous layer was extracted
with EtOAc (5 mL × 3). The EtOAc layer was dried (Na2SO4)
and concentrated. The crude product was purified by column
chromatography to give pure product (47.1 mg, pale yellow
7.87 (s, 1H), 7.74 (s, 1H), 7.61 (d, 1H, J = 7.6 Hz), 7.51-7.41
(m, 2H), 7.12 (s, 2H), 6.89 (d, 1H, J = 8.4 Hz), 6.49 (s, 1H),
13
6.02 (d, 2H, J = 1.6 Hz); C NMR (100 MHz, CDCl3) δ
1
oil) in 98% yield; H NMR (400 MHz, CDCl3) δ 7.79 (s,
148.2, 147.5, 142.4, 141.2, 140.6, 134.7, 129.8, 126.9,
124.9, 120.9, 117.9, 117.6, 108.6, 107.7, 101.3, 29.7; FT-IR
(ATR): 2924, 2853, 2359, 2341, 1586, 1519, 1506, 1468,
1H), 7.71 (s, 1H), 7.44 (d, 2H, J = 8.8 Hz), 6.83 (d, 2H, J =
13
8.4 Hz), 6.45 (s, 1H); C NMR (100 MHz, CDCl3) δ 155.4,
−1
1242, 1222, 1040, 945, 786 cm ; ESIMS: m/z calcd for
140.5, 133.3, 127.7, 121.8, 116.2, 107.2; FT-IR (ATR): 3425,
2922, 2359, 1600, 1524, 1462, 1402, 1274, 1123, 1083, 833,
+
C16H13N2O2 [M+H] 265.09, found 265.20.
−1 +
755 cm ; ESIMS: m/z calcd for C9H9N2O [M+H] 161.06,
(3-Methoxy-3'-(1H-pyrazol-1-yl)biphenyl-4-yl)methanol
1
(2f). White solid; H NMR (400 MHz, CDCl3) δ 8.02 (s,
found 161.06.
1H), 7.97 (s, 1H), 7.79 (s, 1H), 7.70-6.65 (m, 1H), 7.58-7.51
(m, 2H), 7.39 (d, 1H, J = 7.6 Hz), 7.25 (dd, 1H, J = 7.6 Hz,
1.2 Hz), 7.16 (s, 1H), 6.53 (t, 1H, J = 2.0 Hz), 4.77 (d, 2H, J
Acknowledgments. This research was supported by the
KIST Institutional Program, Republic of Korea. This work
was also supported by the Ewha Womans University Research
Grant of 2012. We are grate to Professor Gary A. Molander
(University of Pennsylvania) for his scientific advice.
13
= 5.2 Hz), 3.98 (s, 3H), 2.32 (t, 1H, J = 2.0 Hz); C NMR
(100 MHz, CDCl3) δ 157.8, 142.7, 141.6, 141.2, 140.5,
129.8, 129.1, 128.8, 126.9, 125.3, 119.7, 118.2, 118.1, 109.3,
107.7, 61.9, 55.5; FT-IR (ATR): 3386, 2925, 2854, 2360,
2342, 1605, 1572, 1518, 1397, 1218, 1083, 1044, 947, 787,
References
−1
+
747 cm ; ESIMS: m/z calcd for C17H17N2O2 [M+H] 281.12,
found 281.20.
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−3
(17.3 mg, 5 × 10 mmol, 5 mol %) was added dry methanol
o
(2 mL). The reaction was conducted at 80 C. After 1 h, the
solvent was removed under vacuum. After the reaction was
finished, water (5 mL) was added and organic layer was
extracted with EtOAc (5 mL × 3). The crude product was
purified by column chromatography to give pure product
o 1
(77.3 mg, a white solid) in 90% yield; mp 249.9 C; H
NMR (400 MHz, CDCl3) δ 7.98 (s, 2H), 7.79 (d, 4H, J = 8.0
13
Hz), 7.76 (s, 2H), 7.71 (d, 4H, J = 8.0 Hz), 6.50 (s, 2H); C
NMR (100 MHz, CDCl3) δ 141.2, 139.5, 138.2, 127.9,
126.7, 119.5, 107.8; FT-IR (ATR): 3135, 3119, 1608, 1518,
−1
1498, 1390, 1332, 1049, 935, 814, 760, 744 cm ; ESIMS:
+
m/z calcd for C18H15N4 [M+H] 287.12, found 287.10.
1-(4-Iodophenyl)-1H-pyrazole (4). To a solution of
potassium 4-(1H-pyrazol-1-yl)phenyltrifluoroborate (75.0
mg, 0.3 mmol) in THF and H2O (1 mL, respectively) were
added NaI (45.0 mg, 0.3 mmol) and Chloroamine-T (84.5
mg, 0.3 mmol). The reaction mixture was stirred at rt for 1 h.
The aqueous layer was extracted with EtOAc (5 mL × 3).
The EtOAc layer was dried (Na2SO4) and concentrated. The
crude product was purified by column chromatography to
give pure product (72.9 mg, a white solid) in 90% yield; mp
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1
89.4 C; H NMR (400 MHz, CDCl3) δ 7.90 (s, 1H), 7.76 (d,
2H, J = 8.8 Hz), 7.73 (s, 1H), 7.46 (d, 2H, J = 8.4 Hz), 6.48
13
(s, 1H); C NMR (100 MHz, CDCl3) δ 141.4, 139.9, 138.4,
126.6, 120.8, 108.1, 90.5; FT-IR (ATR): 3149, 3087, 2923,
2852, 1585, 1517, 1487, 1396, 1386, 1334, 1307, 1248,
−1
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+
C9H8IN2 [M+H] 270.97, found 271.10.
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added Oxane (184.4 mg, 0.3 mmol). The reaction mixture

48 Bull. Korean Chem. Soc. 2013, Vol. 34, No. 1
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