Efficient and rapid synthesis of regioselective functionalized potassium 1,2,3-triazoletrifluoroborates via 1,3-dipolar cycloaddition

Article abstract of DOI:10.1016/j.tet.2011.05.126

In this study, we present a previously unreported method of preparing regiospecific organo-[1,2,3]-triazol-1-aryl-trifluoroborates from haloaryltrifluoroborates via a one-pot 1,3-dipolar cycloaddition reaction. We found that the use of either electron-ric

Full text of DOI:10.1016/j.tet.2011.05.126

Tetrahedron 67 (2011) 5556e5563
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Efficient and rapid synthesis of regioselective functionalized potassium
1,2,3-triazoletrifluoroborates via 1,3-dipolar cycloaddition
,
,b,
Krishnavenu Bolla a b, Taejung Kim a, Jung Ho Song a, Seokjoon Lee c, Jungyeob Ham a
*
a MarineChemomics Laboratory, Natural Medicine Center, Korea Institute of Science and Technology, Gangneung 210-340, Republic of Korea
b Department of Medicinal and Pharmaceutical Chemistry, University of Science and Technology, Daejeon 305-350, Republic of Korea
c Department of Basic Science Kwandong, University College of Medicine, Gangneung 210-701, Republic of Korea
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 6 May 2011
Received in revised form 29 May 2011
Accepted 30 May 2011
Available online 2 June 2011
In this study, we present a previously unreported method of preparing regiospecific organo-[1,2,3]-tri-
azol-1-aryl-trifluoroborates from haloaryltrifluoroborates via a one-pot 1,3-dipolar cycloaddition re-
action. We found that the use of either electron-rich or electron-deficient haloaryltrifluoroborates led to
the desired cycloaddition products with good to excellent yields. Furthermore, we successfully carried
out the cross-coupling reactions of the obtained triazoles with various aryl halides by means of the
SuzukieMiyaura reaction in the presence of 3 mol % of Pd(PPh3)4 catalyst in a 20% aqueous 1,4-dioxane
solution at 100 ꢀC; all these reactions yielded complete conversion to the corresponding products. Be-
sides providing a high level of personnel safety, our highly versatile approach allows the preparation of
functionalized organotrifluoborates containing 1,2,3-triazoles with retained functionality.
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
Click chemistry
1,3-Dipolar addition
Functionalized organotrifluoroborates
SuzukieMiyaura cross-coupling
1. Introduction
various reaction conditions, and are thus suitable for the prepara-
tion of more complex organotriflouroborates that may not be easily
The increasing demand in generating libraries for biological
screening in the areas of drug discovery and medicinal chemistry
has led to the research and development of simpler and more ef-
ficient methods for synthesizing heterocylic compounds that are
used in these areas. The 1,2,3-triazole class of heterocycles has
attracted considerable interest because of its anti-microbial,1a anti-
bacterial,1b and anti-HIV1c properties and its wide applications in
various fields, such as organic synthesis,1d material science,1e and
medicinal chemistry.1f,g The method of using Huisgen 1,3-dipolar
cycloaddition of azides and terminal alkynes is widely used in
forming 1,2,3-triazole rings.2aed Sharpless2e and Meldal2f have
initially and independently proposed that the Cu(I)-catalyzed
azide-alkyne cycloaddition (CuAAC) reaction significantly en-
hances the cycloaddition between alkynes and azides, exclusively
affording 1,4-disubstituted 1,2,3-triazole. One of the numerous
features of the CuAAC is its association with the SuzukieMiyaura
cross-coupling reaction.
obtained by conventional syntheses of organoboron reagents.3bed,4
These organotrifluoroborate substrates do not undergo undesirable
side reactions with commonly employed organic bases, acids, and
nucleophiles. Moreover, potassium organotrifluoroborate salts ex-
hibit enhanced stability, and thus they can be prepared and stored
for long periods of time.3a,5
In 2010, Frost and co-workers6 demonstrated the use of azido-
boronate ester motif in a cycloaddition reaction. However, this
example utilizes only benzylazido-boronate ester in the formation
of 1,2,3-triazole. Organic azides are considered explosive in nature;
thus, the isolation or purification of lower organic azides or poly-
azides is difficult.7 Therefore, an appropriate method of the in situ
generation of azides from suitable precursors is required; such
a method can avoid the necessary isolation of organic azides in
conventional methods.
2. Results and discussion
Over the past few years, organotrifluoroborate salts have been
considered as valuable alternatives to boronic acids and boronate
esters used as precursors in the SuzukieMiyaura cross-coupling
reaction.3 Organotrifluoroborates are inert and stable under
In a recent report, we have demonstrated an efficient method
for the preparation of potassium azidoaryltrifluoroborates from the
corresponding haloaryltrifluoroborates (Scheme 1).8
During our research in the preparation of functionalized potas-
sium organotrifluoroborates, we felt that our method of preparing
organo-[1,2,3]-triazol-1-aryl-trifluoroborates from haloaryltri-
fluoroborates via the in situ formation of azidoaryltrifluoroborates
* Corresponding author. Tel.: þ82 33 650 3502; fax: þ82 33 650 3629; e-mail
address: ham0606@kist.re.kr (J. Ham).
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.05.126

K. Bolla et al. / Tetrahedron 67 (2011) 5556e5563
5557
N3
system is effective for both the azidation and the 1,3-dipolar cyclo-
addition. Therefore, a similar two-step one-pot method can be
employed in the preparation of 1-aryl 1,2,3-triazoles from the cor-
responding haloaryltrifluoroborates.
X
NaN3 (1.0 equiv)
10 mol % of CuBr
BF3K
1
( )
BF3K
H
N
20 mol % of
N
H
R
R
Cs2CO3 (1.0 equiv)
In order to explore the scope of the 1,3-dipolar cycloaddition
reaction in our study, we tested other haloaryltrifluoroborates with
different substituents and a selection of terminal alkynes. The re-
sults are summarized in Table 1. As can be observed in Table 1,
a variety of terminal alkynes were tolerated in this one-pot re-
action. Aryl alkynes bearing electron-withdrawing groups such as
flouro and bromo groups (Table 1, entries 3, 7, and 8) underwent the
1,3-dipolar cycloaddition with a good overall reaction rate and
sufficient yield. However, the electron-withdrawing group present
at the meta-position (e.g., the chloro group) showed a slight de-
crease in yield (Table 1, entry 6). In a similar fashion, aryl alkynes
bearing electron-donating groups such as methoxy, methyl, and n-
pentyl groups (Table 1, entries 2, 4, and 5) were obtained in good
yields. On the other hand, alkyl acetylenes also showed higher re-
activity with a variety of functional group tolerances (Table 1, en-
tries 9e14). However, the only the exception is entry 10, where the
reaction with prop-2-ynylcyclohexane resulted in a moderate yield
of 66% due to the steric hindrance. In addition, the strong electron-
withdrawing nitrile group was well tolerated (Table 1, entry 11).
Alkyl acetylenes containing electron-donating groups such as
methoxy and hydroxy groups (Table 1, entries 12e14) completed
the reaction in identical time spans when 1.5 equiv of methyl
propargyl ether was used.
The reaction involving 2-methylbut-3-yn-2-ol sterically hin-
dered hydroxyl group by methyl groups exhibited sufficient re-
activity (Table 1, entry 14); a 95% yield was obtained within 1.5 h.
Moreover, with regards to electromeric effects, the haloaryltri-
fluoroborates showed a decline inproduct yield and observed longer
reaction time with meta-BF3K as compared with BF3K positioned at
the para-position (Table 1, entries 1, 8, and 15). The scope of the
reaction regarding the substituent effect on haloaryltrifluoroborates
was then examined and found that with methoxygroup higher yield
was obtained in less time than with methyl substituent (Table 1,
DMSO / 90 oC
Scheme 1. Preparation of potassium azidoaryltrifluoroborates.
could further be developed into an efficient one-pot procedure. This
method would reduce the safety concerns raised fromworking with
organic azides. The lack of examples detailing a practical method for
our objective and the limitations associated with other boron de-
rivatives prompted us to investigate and explore a general, mild, and
convenient method for the preparation of organo-[1,2,3]-triazol-1-
aryl-trifluoroborates. In this study, we report a one-pot synthesis
of organo-[1,2,3]-triazol-1-aryl-trifluoroborates with a broad range
of alkynes and various haloaryltrifluoroborates. Our approach
(which is the first of its kind) is highly versatile; it allows the prep-
aration of functionalized organotrifluoborate containing 1,2,3-
triazoles with retained functionality.
Firstly, we examined whether our catalyst system for the azida-
tion of haloaryltrifluoroborates has a catalytic effect on the 1,3-
dipolar addition between azidoaryltrifluoroborates and terminal
alkynes. Initially, we carried out the reaction of potassium 4-
iodophenyltrifluoroborate (0.25 mmol) with phenylacetylene (1a,
0.28 mmol) in the presence of NaN3 (0.25 mmol), 10 mol % of CuBr
and 20 mol % of N,N0-dimethylethylenediamine (DMEDA) in DMSO-
d6 as a solvent at 90 ꢀC in an oil bath using a nuclear magnetic res-
onance (NMR) tube for 1 h. The conversion of the reaction was
monitored by 1H NMR at various intervals of time. It was observed
that the conversionreached its end point after1 h. Subsequent tothe
removal of the solvent under high vacuum at 60e70 ꢀC, the desired
salt product was obtained. It is noteworthy that the reaction could be
scaled to 2 mmol, thereby providing product 2a in 98% yield (Table 1,
entry 1). However, when 4-bromophenyltrifluoroborate was used as
a starting material, reaction time was extended to 8.5 h (see
Experimental section). Our results clearly proved that the catalytic
Table 1
One-pot 1,3-dipolar cycloaddition reactionsa
Entry
1
Alkyne
Reaction time (h)
Product
Isolated yield (%)
N
N
N
BF K
3
1.0 (from I)
8.5 (from Br)
98b
95c
1a
2a
N
N
N
BF K
3
2
3
4
1.0
1.5
1.5
90
94
1b
MeO
2b
MeO
N
N
N
BF K
3
2c
1c
F
F
N
N
N
BF K
3
2d
92
1d
Me
(continued on next page)
Me

5558
K. Bolla et al. / Tetrahedron 67 (2011) 5556e5563
Table 1 (continued )
Entry
Alkyne
Reaction time (h)
1.5
Product
Isolated yield (%)
91
N
N
N
BF K
3
1e
5
2e
N
N
Cl
N
BF K
3
6
7
1.5
86
98
1f
2f
Cl
N
N
N
BF K
3
2g
1g
1.0
Br
Br
BF K
3
N
N
N
N
N
N
8
1g
7.0
94c
Br
2h
Br
BF K
3
9
1.5
80
66
1h
2i
N
N
N
BF K
3
10
11
1.5
1i
2j
N
NC
N
N
BF K
3
82b
2k
1j
1.5
NC
N
N
12d
13
1.5
94
82
95
MeO
HO
N
BF K
3
2l
1k
MeO
N
N
N
N
N
BF K
3
2m
1.5
1l
HO
N
BF K
3
2n
14
1.5
1m
HO
HO
BF K
3
N
N
7.0 (from I)
11.0 (from Br)
75
65
N
15c
1a
2o
BF K
3
N
N
N
16c
17c
8.5 (from Br)
80
1a
2p
Me
BF K
3
N
N
N
N
N
N
4.5 (from Br)
12.5 (from Br)
92
75
1a
2q
OMe
BF K
3
18c
1a
2r
Cl
a
All reactions were performed on a 0.25 mmol scale in 1.0 mL of DMSO and monitored by 1H NMR in DMSO-d6.
Reactions were performed on a 2.0 mmol scale.
Initially converted into azide and then alkyne was added, see experimental part for more details.
Methyl propargyl ether (1.5 equiv) as a starting material was used.
b
c
d
entries 16 and 17). When haloaryltrifluoroborates containing
than those obtained with electron-donating substituents (Table 1,
entries 16e18). It was found that the use of either electron-rich or
electron-deficient haloaryltrifluoroborates led to the desired cy-
cloaddition products with good to excellent yields.
electron-withdrawing substituent, such as chloride was chosen for
the reaction process, the reaction went to completion after 12.5 h
(Table 1, entry 18). And, the productivity in these cases was lower

K. Bolla et al. / Tetrahedron 67 (2011) 5556e5563
5559
Next, we attempted to optimize the cross-coupling reaction
conditions using these organotrifluoroborates. As observed in the
optimization studies (Table 2), a 32% yield of the cross-coupling
compound 3a was obtained by using 2a as a model substrate
with 4-bromobenzonitrile under typical conditions when reacting
with Pd(OAc)2 (3 mol %), and K2CO3 as a base in 20% aqueous 1,4-
dioxane solvent system at 80 ꢀC (Table 2, entry 1). When we
attempted to increase the reaction temperature under identical
reaction conditions, the desired product 3a was obtained with
a satisfactory yield of 65% (Table 2, entry 2). However, the use of
Pd(dba)2 as a catalyst in the above reaction resulted in a low yield
(Table 2, entry 3). When further optimization studies were carried
out for the production of 3a, the target compound was obtained in
yields of 72%, 62%, 57%, and 74% using Pd(OAc)2/PPh3, Pd(OAc)2/
Xphos, PdCl2(dppf)$CH2Cl2, and Pd(PPh3)4, respectively (Table 2,
entries 4e7). However, when the reaction was performed with
Pd(PPh3)4 and Cs2CO3 as a base under identical conditions, the
isolated yield of 3a increased to 79% (Table 2, entry 8). Our exam-
ination of solvent effects showed that a 20% aqueous 1,4-dioxane
solution proved to be the optimal solvent system (Table 2, entries
9e11).
yield (Table 3, entry 5), the chosen halide exhibited an enormous
steric effect.
3. Conclusion
In conclusion, regiospecific potassium organo-[1,2,3]-triazol-1-
aryl-trifluoroborates were prepared for the first time from haloar-
yltrifluoroborates via one-pot 1,3-dipolar cycloaddition reactions
with retained functionality. Further, their CeC bond formation by
the SuzukieMiyaura cross-coupling reaction was explored with
various aryl bromides. Our reaction conditions allow the simple
and effective synthesis of potassium organotrifluoroborate con-
taining 1,2,3-triazoles. In addition, our method provides the distinct
advantage of high purity and yields over current methods.
4. Experimental
4.1. General considerations
1H, 13C, and 19F NMR spectra were recorded at 400, 100, and
376 MHz, respectively using Bruker UltraShield Plus 400 MHz/
54 mm instrument. 19F NMR chemical shifts were referenced to
external CFCl3 (0.0 ppm). 11B NMR spectra at 128 MHz were
Table 2
Optimization of reaction conditions for the cross-coupling reaction with triazole-
obtained on
a spectrometer equipped with the appropriate
containing organotrifluoroboratesa
decoupling accessories. All 11B NMR chemical shifts were refer-
enced to external BF3$OEt2 (0.0 ppm) with a negative sign in-
dicating an up field shift. Mass spectra of potassium 1,2,3-
triazoletrifluoroborates were recorded on LCQ Fleet Ion Trap Mass
Spectrometer (ESI-MS) using negative ESI mode at the mass spec-
trometry facilities in KIST-Gangneung Institute. IR spectra were
obtained using Nicolet iS10 FT-IR spectrometer. Reactions were
performed in glass vessels (capacity 10 mL) sealed with a septum.
Melting points were performed on recrystallized solids and recor-
ded on Stanford Research Systems OptiMelt MPA100 melting point
apparatus and are uncorrected. Commercially available reagents
were used without purification unless noted otherwise.
Br
CN
(1.0 quiv)
N
N
3 mol % of Pd cat.
(6 mol % of ligand)
N
N
N
BF K
3
N
CN
base (3.0 equiv)
2a
3a
aq 1,4-dioxane / 100 o
C
Entry
3 mol % Pd
cat./6 mol % ligand
Base
Reaction
time (h)
Isolated
yield (%)
1b
2
3
4
5
6
7
8
Pd(OAc)2
Pd(OAc)2
Pd(dba)2
Pd(OAc)2/PPh3
Pd(OAc)2/XPhos
PdCl2(dppf)$CH2Cl2
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
4
4
4
4
4
4
2
2
2
2
2
32
65
52
72
62
57
74
79
4.2. General procedure I (one-pot 1,3-dipolar cycloaddition
reactions) Table 1
9c
10d
11e
47
Trace
27
Pd(PPh3)4
Pd(PPh3)4
To a solution of potassium haloaryltrifluoroborate (0.25 mmol),
NaN3 (16.3 mg, 0.25 mmol), CuBr (3.6 mg, 10 mol %), Cs2CO3
(81.5 mg, 0.25 mmol), and N,N0-dimethylethylenediamine (4.4 mg,
20 mol %) in DMSO-d6 (1 mL) was added corresponding alkyne
(0.28 mmol, 1.1 equiv) under atmospheric conditions. The reaction
mixture was heated in an oil bath at 90 ꢀC until the 1H NMR (in
DMSO-d6) indicated completion of the reaction (see Table 1). After
completion of the reaction, the solvent was removed in vacuum at
60e70 ꢀC. The residual product was dissolved in dry acetone
(3 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 vacuum to afford the desired pure product.
a
All reaction was performed on a 0.1 mmol scale in 0.6 mL of 20% aqueous 1,4-
dioxane at 100 ꢀC in an oil bath.
b
Reaction temperature was 80 ꢀC.
c
Reaction was performed in methanol at 65 ꢀC.
d
Reaction solvent was 20% aqueous toluene.
Reaction solvent was 20% aqueous DMF.
e
Having obtained the above optimal reaction conditions, we ex-
amined the SuzukieMiyaura cross-coupling reaction of various
triazoles containing organotrifluoroborates with aryl, pyridyl and
alkenyl bromides. All the reactions yielded complete conversion to
the corresponding products. The results are presented in Table 3.
As expected, the coupling reactions led to the corresponding
products in good to excellent yields within short reaction times. In
the case of 4-bromoanisole (Table 3, entry 2), there is slight decrease
in yield when compared with that of 4-bromobenzonitrile (Table 3,
entry 1), therebyshowing the impactof the electron releasingeffects
involved in the former reaction. In order to study the efficiency of
this cross-coupling condition, when 2-bromopyridine was used to
couple with 2a to produce 3c, a slight decrease inyield was observed
in this case (Table 3, entry 3). When we used triazole 2k, a higher
yield was obtained with the previously used 4-bromobenzonitrile
compound (Table 3, entry 4). Finally, when we tested the reactivity
of the triazole 2k with bromotriphenylethylene, it was noteworthy
that though the reaction completed within 2 h with an 87% product
4.2.1. Potassium
4-(4-phenyl-1H-1,2,3-triazol-1-yl)phenyltrifluoro-
borate (2a, 2.0 mmol scale reaction from I). General procedure I was
used employing potassium 4-iodophenyltrifluoroborate (620 mg,
2.0 mmol), NaN3 (130.0 mg, 2.0 mmol), CuBr (28.7 mg, 10 mol %),
Cs2CO3 (651.8 mg, 2.0 mmol), N,N0-dimethylethylenediamine
(35.3 mg, 20 mol %), and ethynylbenzene (1a, 225 mg, 2.2 mmol) in
DMSO-d6 (8 mL), to give the desired product in 98% yield (641 mg,
1
a light brown solid). Mp¼206e208 ꢀC H NMR (400 MHz, acetone-
d6)
d
8.89 (s, 1H), 8.02 (d, 2H, J¼6.8 Hz), 7.69 (m, 4H), 7.48 (t, 2H,
J¼7.6 Hz), 7.38 (m, 1H). 13C NMR (100 MHz, acetone-d6)
d 147.4,135.0,
132.7, 131.2, 128.7, 127.8, 125.4, 118.4, 118.1. 19F NMR (376 MHz, ace-
tone-d6)
d
ꢁ142.3. 11B NMR (128 MHz, acetone-d6)
d 3.43. FT-IR

5560
K. Bolla et al. / Tetrahedron 67 (2011) 5556e5563
Table 3
SuzukieMiyaura cross-coupling reactionsa
Entry
1
Triazole/BF3K
R-Br
Product
Reaction time (h)
2
Isolated yield (%)
79
N
N
N
N
N
N
N
CN
2a
Br
CN
3a
3b
3c
N
N
OMe
2
3
4
2a
2a
2k
2
3
3
75
65
82
Br
OMe
N
Br
N
N
N
N
N
CN
3d
Br
Br
CN
NC
NC
N
87
N
5
2k
2
3e
a
All reaction were performed on a 0.5 mmol scale in 2.0 mL of 20% aqueous 1,4-dioxane according to the optimized conditions of entry 8 in Table 2.
3
2
(ATR): 3129, 2081,1603,1514,1482,1455,1428,1396,1215, 1094, 965,
828, 759, 690 cmꢁ1. ESI-MS: m/z calcd for C14H10BF3N3 [MꢁKþ]ꢁ
288.09, found 288.29.
127.4 (d, JCF¼8.1 Hz), 118.5, 118.1, 115.5 (d, JCF¼21.7 Hz). 19F NMR
(376 MHz, acetone-d6þDMSO-d6)
(128 MHz, acetone-d6þDMSO-d6)
d
ꢁ115.7, ꢁ141.7. 11B NMR
d
3.24. FT-IR (ATR): 3135, 2916,
2849, 1603, 1559, 1494, 1438, 1397, 1207, 1158, 1026, 1010, 957,
822 cmꢁ1. ESI-MS: m/z calcd for C14H9BF4N3 [MꢁKþ]ꢁ 306.08,
found 306.11.
4.2.2. Potassium
4-(4-phenyl-1H-1,2,3-triazol-1-yl)phenyltrifluoro-
borate (2a, 0.25 mmol scale reaction from Br). A solution of potassium
4-bromophenyltrifluoroborate (65.7 mg, 0.25 mmol), NaN3 (16.2 mg,
0.25 mmol), CuBr (3.6 mg, 10 mol %), Cs2CO3 (81.4 mg, 0.25 mmol),
and N,N0-dimethylethylenediamine (4.4 mg, 20 mol %) in DMSO-d6
(1 mL) was heated in an oil bath at 90 ꢀC for 7 h monitored by the 1H
NMR (in DMSO-d6) until the complete conversion of the starting
material into azide8 and then added ethynylbenzene (1a, 28.6 mg,
0.28 mmol) into the reaction mass and continued for another 1.5 h
(see Table 1). After completion of the reaction, work-up was adopted
as mentioned in General procedure I, to give the desired product in
95% yield (65.9 mg, a light brown solid).
4.2.5. Potassium
(4-p-tolyl-1H-1,2,3-triazol-1-yl)phenyltrifluoro-
borate (2d). General procedure I was used employing potassium 4-
iodophenyltrifluoroborate (77.5 mg, 0.25 mmol) and 1-ethynyl-4-
methylbenzene (1d, 32.5 mg, 0.28 mmol), to give the desired prod-
uct in 92% yield (78.5 mg, a light brown solid). Mp¼204e210 ꢀC. 1H
NMR (400 MHz, acetone-d6)
d
8.81 (s,1H), 7.90 (d, 2H, J¼8.0 Hz), 7.69
(d, 2H, J¼8.4 Hz), 7.66 (d, 2H, J¼8.4 Hz), 7.29 (d, 2H, J¼8.0 Hz), 2.38 (s,
3H). 13C NMR (100 MHz, acetone-d6)
d
147.5, 137.4, 134.9, 132.7, 129.3,
128.5, 125.4, 118.1, 118.0, 20.3. 19F NMR (376 MHz, acetone-d6)
d
ꢁ142.3. 11B NMR (128 MHz, acetone-d6)
d 3.07. FT-IR (ATR): 3408,
4.2.3. Potassium 4-(4-(4-methoxyphenyl)-1H-1,2,3-triazol-1-yl)phe-
nyltrifluoroborate (2b). General procedure I was used employing
potassium 4-iodophenyltrifluoroborate (77.5 mg, 0.25 mmol) and
1-ethynyl-4-methoxybenzene (1b, 37.0 mg, 0.28 mmol), to give the
desired product in 90% yield (80.4 mg, a light brown solid).
3131, 3043, 2918, 2855, 2258, 2120, 1914, 1604, 1496, 1436, 1396,
1377, 1343, 1215, 1110, 1026, 961, 826 cmꢁ1. ESI-MS: m/z calcd for
C15H12BF3N3 [MꢁKþ]ꢁ 302.10, found 302.07.
4.2.6. Potassium
4-(4-(4-pentylphenyl)-1H-1,2,3-triazol-1-yl)phe-
Mp¼195 ꢀC (dec). 1H NMR (400 MHz, acetone-d6)
d
8.77 (s,1H), 7.94
nyltrifluoroborate (2e). General procedure I was used employing
potassium 4-iodophenyltrifluoroborate (77.5 mg, 0.25 mmol) and
1-ethynyl-4-pentylbenzene (1e, 48.2 mg, 0.28 mmol), to give the
desired product in 91% yield (90.4 mg, an ivory solid).
(d, 2H, J¼8.4 Hz), 7.66 (m, 4H), 7.04 (d, 2H, J¼8.8 Hz), 3.86 (s, 3H).
13C NMR (100 MHz, acetone-d6)
d 160.5, 147.6, 135.8, 133.5, 127.6,
124.7, 118.9, 118.3, 115.0, 55.6. 19F NMR (376 MHz, acetone-d6)
d
ꢁ142.4. 11B NMR (128 MHz, acetone-d6)
d
3.22. FT-IR (ATR): 3621,
Mp¼257e262 ꢀC. 1H NMR (400 MHz, acetone-d6)
d 8.81 (s,1H), 7.92
3136, 2942, 2838, 2206, 2164, 2037, 1605, 1563, 1496, 1467, 1439,
(d, 2H, J¼8.4 Hz), 7.69 (d, 2H, J¼8.4), 7.65 (9d, 2H, J¼8.4 Hz), 7.31 (d,
2H, J¼8.4 Hz), 2.67 (t, 2H, J¼7.2 Hz), 1.67 (m, 2H), 1.36 (m, 4H),
1396, 1306, 1219, 1178, 1108, 1093, 1027, 965, 830, 611, 536 cmꢁ1
.
ESI-MS: m/z calcd for C15H12BF3N3O [MꢁKþ]ꢁ 318.10, found 318.18.
0.91(t, 3H, J¼6.8 Hz). 13C NMR (100 MHz, acetone-d6)
d 147.5, 142.5,
134.9, 132.7 (x2), 128.7, 125.4, 118.0 (x2), 35.3, 31.3, 31.0, 22.2, 13.3.
4.2.4. Potassium
4-(4-(4-fluorophenyl)-1H-1,2,3-triazol-1-yl)phe-
19F NMR (376 MHz, acetone-d6)
d
ꢁ141.6. 11B NMR (128 MHz, ace-
nyltrifluoroborate (2c). General procedure I was used employing
potassium 4-iodophenyltrifluoroborate (77.5 mg, 0.25 mmol) and
1-ethynyl-4-fluorobenzene (1c, 33.6 mg, 0.28 mmol), to give the
tone-d6) d 3.24. FT-IR (ATR): 3127, 2947, 2927, 2855, 1603, 1514,
1495, 1436, 1396, 1207, 1026, 1010, 965, 830 cmꢁ1. ESI-MS: m/z calcd
for C19H20BF3N3 [MꢁKþ]ꢁ 358.17, found 358.13.
desired product in 94% yield (81.1 mg,
a light gray solid).
Mp¼247e251 ꢀC. 1H NMR (400 MHz, acetone-d6þDMSO-d6)
d
8.93
4.2.7. Potassium
4-(4-(3-chlorophenyl)-1H-1,2,3-triazol-1-yl)phe-
(s, 1H), 8.76 (dd, 2H, J¼8.8, 5.2 Hz), 7.69 (d, 2H, J¼8.4 Hz), 7.66 (d,
nyltrifluoroborate (2f). General procedure I was used employing
potassium 4-iodophenyltrifluoroborate (77.5 mg, 0.25 mmol) and
1-chloro-3-ethynylbenzene (1f, 38.2 mg, 0.28 mmol), to give the
2H, J¼8.4 Hz), 7.26 (t, 2H, J¼8.8 Hz). 13C NMR (100 MHz, acetone-
d6þDMSO-d6)
d
162.4 (d, 1JCF¼243.4 Hz), 146.5, 134.8, 132.7, 127.8,

K. Bolla et al. / Tetrahedron 67 (2011) 5556e5563
5561
desired product in 86% yield (77.7 mg, a light purple solid).
Mp¼210e212 ꢀC. 1H NMR (400 MHz, acetone-d6)
d
8.17 (s, 1H), 7.64
Mp¼252 ꢀC (dec). 1H NMR (400 MHz, acetone-d6)
d
8.98 (s, 1H),
(d, 2H, J¼8.4 Hz), 7.58 (d, 2H, J¼8.4 Hz), 2.63 (d, 2H, J¼7.2 Hz), 1.72
8.05 (s, 1H), 7.98 (d, 1H, J¼7.6 Hz), 7.70 (d, 2H, J¼8.4 Hz), 7.67 (d, 2H,
(m, 6H), 1.24 (m, 3H), 1.02 (m, 2H). 13C NMR (100 MHz, acetone-d6)
J¼8.4 Hz), 7.51 (t, 1H, J¼8.0 Hz), 7.40 (m, 1H). 13C NMR (100 MHz,
d
146.5, 135.1, 132.6, 119.6, 117.9, 38.0, 33.1, 32.8, 26.2, 26.0. 19F NMR
acetone-d6)
d
148.6, 146.0, 134.2, 133.3, 132.7, 130.5, 127.6, 125.1,
(376 MHz, acetone-d6)
d
ꢁ142.0. 11B NMR (128 MHz, acetone-d6)
123.8, 119.2, 118.15. 19F NMR (376 MHz, acetone-d6)
NMR (128 MHz, acetone-d6)
d
ꢁ141.7. 11B
d 3.31. FT-IR (ATR): 3374, 3135, 3037, 2920, 2849, 2660, 2125, 2007,
d
3.29. FT-IR (ATR): 3648, 3607, 3128,
1603, 1515, 1447, 1397, 1223, 1193, 955, 817, 726 cmꢁ1. ESI-MS: m/z
calcd for C15H18BF3N3 [MꢁKþ]ꢁ 308.15, found 308.16.
2357, 1603, 1573, 1515, 1473, 1442, 1395, 1215, 1104, 1079, 1025, 961,
826, 771, 730, 685, 629, 570 cmꢁ1
. ESI-MS: m/z calcd for
C14H9BClF3N3 [MꢁKþ]ꢁ 322.05, found 322.06.
4.2.12. Potassium 4-(4-(3-cyanopropyl)-1H-1,2,3-triazol-1-yl)phe-
nyltrifluoroborate (2k, 2.0 mmol scale reaction). General procedure I
was used employing potassium 4-iodophenyltrifluoroborate
(620 mg, 2.0 mmol), NaN3 (130.0 mg, 2.0 mmol), CuBr (28.7 mg,
10 mol %), Cs2CO3 (651.8 mg, 2.0 mmol), N,N0-dimethylethylenedi-
amine (35.3 mg, 20 mol %), and hex-5-ynenitrile (1j, 205 mg,
2.2 mmol) in DMSO-d6 (8 mL), to give the desired product in 82%
yield (522 mg, a light brown solid). Mp¼208 ꢀC (dec). 1H NMR
4.2.8. Potassium 4-(4-(4-bromophenyl)-1H-1,2,3-triazol-1-yl)phe-
nyltrifluoroborate (2g). General procedure I was used employing
potassium 4-iodophenyltrifluoroborate (77.5 mg, 0.25 mmol) and
1-bromo-4-ethynylbenzene (1 g, 50.6 mg, 0.28 mmol), to give the
desired product in 98% yield (99.5 mg, a brown solid). Mp¼267 ꢀC
(dec). 1H NMR (400 MHz, acetone-d6)
d 8.94 (s, 1H), 7.97 (d, 2H,
J¼8.4 Hz), 7.69 (d, 2H, J¼8.4 Hz), 7.67 (d, 2H, J¼8.4 Hz), 7.65 (d, 2H,
(400 MHz, acetone-d6þDMSO-d6)
d 8.33 (s, 1H), 7.65 (d, 2H,
J¼8.4 Hz), 7.59 (d, 2H, J¼8.0 Hz), 2.91 (t, 2H, J¼7.6 Hz), 2.62 (t, 2H,
J¼8.0 Hz). 13C NMR (100 MHz, acetone-d6)
d
146.3, 134.7, 132.7,
131.8,130.5,127.3,121.0,118.8,118.1. 19F NMR (376 MHz, acetone-d6)
J¼7.2 Hz), 2.09 (m, 2H). 13C NMR (100 MHz, acetone-d6þDMSO-d6)
d
ꢁ142.1. 11B NMR (128 MHz, acetone-d6)
d
3.30. FT-IR (ATR): 3426,
d 151.8, 146.2, 135.0, 132.6, 119.8, 119.7, 118.0, 53.2, 25.2, 24.2, 15.8.
3127, 2933, 2200, 2129, 2040, 1603, 1548, 1515, 1479, 1436, 1397,
1218, 1071, 1027, 969, 827, 739, 718, 627 cmꢁ1. ESI-MS: m/z calcd for
C14H9BBrF3N3 [MꢁKþ]ꢁ 366.00, found 366.23.
19F NMR (376 MHz, acetone-d6þDMSO-d6)
d
ꢁ141.9. 11B NMR
(128 MHz, acetone-d6þDMSO-d6)
d 3.28. FT-IR (ATR): 3420, 3120,
3083, 3039, 2945, 2245, 1601, 1552, 1519, 1463, 1436, 1419, 1340,
1325, 1226, 1212, 1189, 1057, 1025, 964, 939, 844, 823 cmꢁ1. ESI-MS:
m/z calcd for C12H11BF3N4 [MꢁKþ]ꢁ 279.10, found 279.33.
4.2.9. Potassium 3-(4-(4-bromophenyl)-1H-1,2,3-triazol-1-yl)phe-
nyltrifluoroborate (2h). General procedure I was used employing
potassium 3-iodophenyltrifluoroborate (77.5 mg, 0.25 mmol), NaN3
(16.3 mg, 0.25 mmol), CuBr (3.6 mg, 10 mol %), Cs2CO3 (81.4 mg,
0.25 mmol), and N,N0-dimethylethylenediamine (4.4 mg, 20 mol %)
in DMSO-d6 (1 mL) was heated in an oil bath at 90 ꢀC for 6 h
monitored by the 1H NMR (in DMSO-d6) until the complete
conversion of the starting material into azide8 and then added
1-bromo-4-ethynylbenzene (1g, 50.6 mg, 0.28 mmol) into the re-
action mass and continued for another 1 h (see Table 1). After
completion of the reaction, work-up was adopted as mentioned in
General procedure I, to give the desired product in 94% yield
(95.4 mg, a brown solid). Mp¼264 ꢀC (dec). 1H NMR (400 MHz,
4.2.13. Potassium 4-(4-(methoxymethyl)-1H-1,2,3-triazol-1-yl)phe-
nyltrifluoroborate (2l). General procedure I was used employing
potassium 4-iodophenyltrifluoroborate (77.5 mg, 0.25 mmol) and
3-methoxyprop-1-yne (1k, 26.6 mg, 0.38 mmol), to give the de-
sired product in 94% yield (70.0 mg,
a light purple solid).
Mp¼195e198 ꢀC. 1H NMR (400 MHz, acetone-d6)
d 8.38 (s, 1H), 7.66
(d, 2H, J¼8.4 Hz), 7.59 (d, 2H, J¼8.0 Hz), 4.58 (s, 2H), 3.37 (s, 3H). 13C
NMR (100 MHz, acetone-d6) d 145.0, 134.9, 132.7, 132.6, 121.1, 118.2,
65.4, 57.0. 19F NMR (376 MHz, acetone-d6)
(128 MHz, acetone-d6)
d
ꢁ140.4. 11B NMR
d
3.29. FT-IR (ATR): 3668, 3612, 3605, 3585,
3565, 3530, 3497, 3486, 3456, 3430, 3415, 3387, 3348, 3139, 2933,
2899, 1603, 1515, 1456, 1437, 1369, 1207, 1189, 1100, 1048, 955, 826,
803, 771 cmꢁ1. ESI-MS: m/z calcd for C10H10BF3N3O [MꢁKþ]ꢁ
256.08, found 256.41.
acetone-d6)
d
8.97 (s, 1H), 8.01 (d, 2H, J¼8.4 Hz), 7.66 (d, 2H,
J¼8.4 Hz), 7.62 (m, 2H), 7.34 (t, 1H, J¼7.6 Hz). 13C NMR (100 MHz,
acetone-d6)
d 146.3, 135.8, 132.2, 131.8, 130.6, 127.4, 127.3, 123.1,
121.0,119.0,117.1. 19F NMR (376 MHz, acetone-d6)
(128 MHz, acetone-d6)
d
ꢁ142.8. 11B NMR
d
3.32. FT-IR (ATR): 3392, 3071, 2132, 2010,
4.2.14. Potassium 4-(4-(hydroxymethyl)-1H-1,2,3-triazol-1-yl)phe-
nyltrifluoroborate (2m). General procedure I was used employing
potassium 4-iodophenyltrifluoroborate (77.5 mg, 0.25 mmol) and
prop-2-yn-1-ol (1l, 15.7 mg, 0.28 mmol), to give the desired prod-
uct in 82% yield (57.6 mg, a light brown solid). Mp¼212 ꢀC (dec). 1H
1579, 1461, 1237, 1209, 1178, 1100, 1068, 1023, 1009, 964, 882, 848,
811, 784, 759, 697, 669, 607 cmꢁ1
. ESI-MS: m/z calcd for
C14H9BBrF3N3 [MꢁKþ]ꢁ 366.00, found 366.21.
4.2.10. Potassium 4-(4-butyl-1H-1,2,3-triazol-1-yl)phenyltrifluoro-
borate (2i). General procedure I was used employing potassium 4-
iodophenyltrifluoroborate (77.5 mg, 0.25 mmol) and 1-hexyne (1h,
23.0 mg, 0.28 mmol), to give the desired product in 80% yield
(61.4 mg, an ivory solid). Mp¼251e255 ꢀC. 1H NMR (400 MHz, ac-
NMR (400 MHz, acetone-d6þDMSO-d6)
d 8.32 (s, 1H), 7.66 (d, 2H,
J¼8.0 Hz), 7.58 (d, 2H, J¼8.0 Hz), 4.72 (s, 2H). 13C NMR (100 MHz,
acetone-d6þDMSO-d6)
d
149.0, 135.0, 132.7, 120.2, 118.1, 55.7. 19F
NMR (376 MHz, acetone-d6þDMSO-d6)
d
ꢁ140.8. 11B NMR
(128 MHz, acetone-d6þDMSO-d6)
d
3.21. FT-IR (ATR): 3149, 2876,
etone-d6)
d
8.17 (s, 1H), 7.64 (d, 2H, J¼8.4 Hz), 7.57 (d, 2H, J¼8.0 Hz),
1913, 1602, 1580, 1516, 1466, 1435, 1399, 1215, 1193, 1063, 955, 938,
2.75 (t, 2H, J¼7.6 Hz), 1.70 (m, 2H), 1.43 (m, 2H) 0.96 (t, 3H,
825, 813, 760, 733, 624, 553 cmꢁ1
. ESI-MS: m/z calcd for
J¼7.2 Hz). 13C NMR (100 MHz, acetone-d6)
d
148.0, 135.2, 132.6,
C9H8BF3N3O [MꢁKþ]ꢁ 242.07, found 242.46.
119.0, 117.9, 31.4, 25.0, 22.0, 13.2. 19F NMR (376 MHz, acetone-d6)
d
ꢁ141.7. 11B NMR (128 MHz, acetone-d6)
d
3.35. FT-IR (ATR): 3139,
4.2.15. Potassium 4-(4-(2-hydroxypropan-2-yl)-1H-1,2,3-triazol-1-
yl)phenyltrifluoroborate (2n). General procedure I was used
2958, 2931, 2860, 1928, 1603, 1552, 1513, 1465, 1432, 1395, 1220,
1191, 962, 826, 730, 625 cmꢁ1. ESI-MS: m/z calcd for C12H14BF3N3
[MꢁKþ]ꢁ 268.12, found 268.14.
employing potassium 4-iodophenyltrifluoroborate (77.5 mg,
0.25 mmol) and 2-methylbut-3-yn-2-ol (1m, 23.5 mg, 0.28 mmol),
to give the desired product in 95% yield (73.4 mg, a brown solid).
4.2.11. Potassium 4-(4-(cyclohexylmethyl)-1H-1,2,3-triazol-1-yl)phe-
nyltrifluoroborate (2j). General procedure I was used employing
potassium 4-iodophenyltrifluoroborate (77.50 mg, 0.25 mmol) and
prop-2-ynylcyclohexane (1i, 34.2 mg, 0.28 mmol), to give the de-
sired product in 66% yield (57.3 mg, an ivory solid).
Mp¼253 ꢀC (dec). 1H NMR (400 MHz, acetone-d6þDMSO-d6)
d 8.24
(s, 1H), 7.65 (d, 2H, J¼8.4 Hz), 7.58 (d, 2H, J¼8.0 Hz), 4.40 (br s, 1H),
1.61 (s, 6H). 13C NMR (100 MHz, acetone-d6þDMSO-d6)
d 156.8,
135.1, 132.7, 118.1, 118.0, 67.5, 30.3. 19F NMR (376 MHz, acetone-
d6þDMSO-d6)
d
ꢁ141.2. 11B NMR (128 MHz, acetone-d6þDMSO-d6)

5562
K. Bolla et al. / Tetrahedron 67 (2011) 5556e5563
d
3.28. FT-IR (ATR): 3270, 3153, 2982, 2934, 2120, 1601, 1508, 1462,
0.25 mmol), and N,N0-dimethylethylenediamine (4.4 mg, 20 mol %)
in DMSO-d6 (1 mL) was heated in an oil bath at 90 ꢀC for 4 h
monitored by the 1H NMR (in DMSO-d6) until the complete con-
version of the starting material into azide8 and then added ethy-
nylbenzene (1a, 28.6 mg, 0.28 mmol) into the reaction mass and
continued for another 0.5 h (see Table 1). After completion of the
reaction, work-up was adopted as mentioned in General procedure
I, to give the desired product in 92% yield (82.2 mg, a dark brown
solid). Mp¼253 ꢀC (dec). 1H NMR (400 MHz, acetone-d6þmetanol-
1392, 1377, 1363, 1206, 1170, 1054, 1027, 956, 827, 804, 730, 613,
566 cmꢁ1. ESI-MS: m/z calcd for C11H12BF3N3O [MꢁKþ]ꢁ 270.10,
found 270.10.
4.2.16. Potassium 3-(4-phenyl-1H-1,2,3-triazol-1-yl)phenyltrifluo-
roborate (2o from I). A solution of potassium 3-iodophenyltri-
fluoroborate (77.5 mg, 0.25 mmol), NaN3 (16.3 mg, 0.25 mmol),
CuBr (3.6 mg, 10 mol %), Cs2CO3 (81.5 mg, 0.25 mmol), and N,N0-
dimethylethylenediamine (4.4 mg, 20 mol %) in DMSO-d6 (1 mL)
was heated in an oil bath at 90 ꢀC for 6 h monitored by the 1H NMR
(in DMSO-d6) until the complete conversion of the starting material
into azide8 and then added ethynylbenzene (1a, 28.6 mg,
0.28 mmol) into the reaction mass and continued for another 1 h
(see Table 1). After completion of the reaction, work-up was
adopted as mentioned in General procedure I, to give the desired
product in 75% yield (61.3 mg, a brown solid). Mp¼243 ꢀC (dec). 1H
d4)
d
8.91 (s, 1H), 8.01 (d, 2H, J¼7.6 Hz), 7.56 (s, 1H), 7.46 (t, 2H,
J¼7.2 Hz), 7.35 (t, 1H, J¼7.2 Hz), 7.25 (s, 1H), 7.20 (s, 1H), 3.84 (s, 3H).
13C NMR (100 MHz, acetone-d6þmetanol-d4)
d 159.5, 147.5, 136.8,
130.9, 128.7, 127.9, 125.4, 118.8, 117.2, 115.3, 103.3, 54.6. 19F NMR
(376 MHz, acetone-d6þmetanol-d4)
d
ꢁ141.8. 11B NMR (128 MHz,
acetone-d6þmetanol-d4)
d
3.30. FT-IR (ATR): 3166, 2936, 2832,
1661,1582,1441,1428,1397,1319,1279,1250,1220,1171,1099,1023,
987, 859, 794, 766, 695, 618 cmꢁ1
. ESI-MS: m/z calcd for
NMR (400 MHz, acetone-d6þDMSO-d6)
d
8.99 (s, 1H), 8.06 (m, 2H),
C15H12BF3N3O [MꢁKþ]ꢁ 318.10, found 318.39.
7.94 (m, 1H), 7.62 (m, 2H), 7.47 (t, 2H, J¼7.6 Hz), 7.36 (m, 2H). 13C
NMR (100 MHz, acetone-d6þDMSO-d6)
d
147.4, 136.0, 132.1, 131.3,
4.2.20. Potassium 3-chloro-5-(4-phenyl-1H-1,2,3-triazol-1-yl)phe-
nyltrifluoroborate (2r). A solution of potassium 3-bromo-5-
chlorophenyltrifluoroborate (74.3 mg, 0.25 mmol), NaN3 (16.3 mg,
0.25 mmol), CuBr (3.6 mg, 10 mol %), Cs2CO3 (81.5 mg, 0.25 mmol),
and N,N0-dimethylethylenediamine (4.4 mg, 20 mol %) in DMSO-d6
(1 mL) was heated in an oil bath at 90 ꢀC for 12 h monitored by the
1H NMR (in DMSO-d6) until the complete conversion of the starting
material into azide8 and then added ethynylbenzene (1a, 28.6 mg,
0.28 mmol) into the reaction mass and continued for another 0.5 h
(see Table 1). After completion of the reaction, work-up was
adopted as mentioned in General procedure I, to give the desired
product in 75% yield (67.8 mg, a greenish brown solid). Mp¼253 ꢀC
128.7, 127.8, 127.4, 125.5, 123.1, 118.8, 117.1. 19F NMR (376 MHz, ac-
etone-d6þDMSO-d6)
d
ꢁ141.5. 11B NMR (128 MHz, acetone-
d6þDMSO-d6)
d
3.09. FT-IR (ATR): 3393, 3150, 2110, 2043, 1644,
1606, 1582, 1474, 1446, 1429, 1248, 1213, 1175, 1072, 1022, 960, 884,
822, 791, 755, 693, 602 cmꢁ1. ESI-MS: m/z calcd for C14H10BF3N3
[MꢁKþ]ꢁ 288.09, found 287.98.
4.2.17. Potassium
3-(4-phenyl-1H-1,2,3-triazol-1-yl)phenyltrifluo-
roborate (2o from Br). A solution of potassium 3-bromopheny-
ltrifluoroborate (65.7 mg, 0.25 mmol), NaN3 (16.3 mg, 0.25 mmol),
CuBr (3.6 mg, 10 mol %), Cs2CO3 (81.5 mg, 0.25 mmol), and N,N0-
dimethylethylenediamine (4.4 mg, 20 mol %) in DMSO-d6 (1 mL)
was heated in an oil bath at 90 ꢀC for 9 h monitored by the 1H NMR
(in DMSO-d6) until the complete conversion of the starting material
into azide8 and then added ethynylbenzene (1a, 28.6 mg,
0.28 mmol) into the reaction mass and continued for another 3 h
(see Table 1). After completion of the reaction, work-up was
adopted as mentioned in General procedure I, to give the desired
product in 65% yield (53.1 mg, a brown solid).
(dec). 1H NMR (400 MHz, acetone-d6)
d 9.02 (s, 1H), 8.05 (d, 2H,
J¼7.6 Hz), 7.89 (s, 1H), 7.73 (s, 1H), 7.57 (s, 1H), 7.48 (t, 3H, J¼7.6 Hz),
7.37 (t, 1H, J¼7.2 Hz). 13C NMR (100 MHz, acetone-d6)
d 148.5, 137.9,
134.0, 132.4, 131.9, 129.8, 129.7, 129.4, 128.8, 128.0, 126.4, 122.0,
119.6, 117.8. 19F NMR (376 MHz, acetone-d6)
(128 MHz, acetone-d6)
d
ꢁ141.1. 11B NMR
d
2.63. FT-IR (ATR): 3156, 3061, 1576, 1473,
1424, 1393, 1211, 1168, 1099, 1026, 1000, 979, 872, 788, 763, 690,
612, 559 cmꢁ1. ESI-MS: m/z calcd for C14H9BClF3N3 [MꢁKþ]ꢁ
322.05, found 322.64.
4.2.18. Potassium 3-methyl-5-(4-phenyl-1H-1,2,3-triazol-1-yl)phe-
nyltrifluoroborate (2p). A solution of potassium 3-bromo-5-
4.3. General procedure II (SuzukieMiyaura cross-coupling
methylphenyltrifluoroborate
(69.2 mg,
0.25 mmol),
NaN3
reactions) Table 3
(16.3 mg, 0.25 mmol), CuBr (3.6 mg, 10 mol %), Cs2CO3 (81.5 mg,
0.25 mmol), and N,N0-dimethylethylenediamine (4.4 mg, 20 mol %)
in DMSO-d6 (1 mL) was heated in an oil bath at 90 ꢀC for 8 h
monitored by the 1H NMR (in DMSO-d6) until the complete con-
version of the starting material into azide8 and then added ethy-
nylbenzene (1a, 28.6 mg, 0.28 mmol) into the reaction mass and
continued for another 0.5 h (see Table 1). After completion of the
reaction, work-up was adopted as mentioned in General procedure
I, to give the desired product in 80% yield (68.2 mg, a dark brown
To a 16ꢂ90 mm glass vessel containing a stirring bar were
added potassium 1,2,3-triazoletrifluoroborate (2a or 2k, 0.5 mmol),
Cs2CO3 (195 mg, 1.5 mmol), Pd(PPh3)4 (3.5 mg, 3 mol %), and aryl
bromide (0.5 mmol). The mixture was dissolved in 20% aqueous
1,4-dioxane (2 mL). The reaction was stirred in an oil bath at 100 ꢀC.
After the aryl bromide was totally consumed (the reaction was
monitored by TLC), then cooled to room temperature. The reaction
mixture was extracted with ethyl acetate and then combined or-
ganic layers were washed with H2O. Finally organic layer was dried
over MgSO4. The solvent was filtered off through silica gel. The
solvent was concentrated on a rotary evaporator. The crude product
was purified by preparative TLC (0.5 mm, elution with hexane/
EtOAc¼3:1). The pure compound 3 was obtained as a white solid.
solid). Mp¼238.0 ꢀC (dec). 1H NMR (400 MHz, acetone-d6)
d 8.85 (s,
1H), 8.04 (d, 2H, J¼7.6 Hz), 7.72 (s, 1H), 7.47 (m, 4H), 7.35 (t, 1H,
J¼7.6 Hz), 2.38 (s, 3H). 13C NMR (100 MHz, acetone-d6)
d 147.3,
136.7, 136.0, 133.0, 131.4, 128.7, 127.7, 125.4, 120.3, 118.5, 117.7, 20.6.
19F NMR (376 MHz, acetone-d6)
tone-d6)
d
ꢁ141.9. 11B NMR (128 MHz, ace-
d
3.33. FT-IR (ATR): 3612, 3150, 3061, 2921, 2853, 2358,
1608, 1590, 1467, 1434, 1377, 1352, 1276, 1236, 1171, 1024, 993, 970,
868, 763, 694, 614 cmꢁ1. ESI-MS: m/z calcd for C15H12BF3N3
[MꢁKþ]ꢁ 302.10, found 302.06.
4.3.1. 40-(4-Phenyl-1H-1,2,3-triazol-1-yl)biphenyl-4-carbonitrile
(3a). General procedure II was used employing potassium 4-(4-
phenyl-1H-1,2,3-triazol-1-yl)phenyltrifluoroborate (2a, 163.5 mg,
0.5 mmol) and 4-bromobenzonitrile (91 mg, 0.5 mmol) to give the
desired product in 79% yield (127.3 mg, an ivory solid).
Mp¼215e218 ꢀC (lit.8 mp¼215e219 ꢀC). 1H NMR (400 MHz, CDCl3)
4.2.19. Potassium 3-methoxy-5-(4-phenyl-1H-1,2,3-triazol-1-yl)phe-
nyltrifluoroborate (2q). A solution of potassium 3-bromo-5-
methoxyphenyltrifluoroborate (73.2 mg, 0.25 mmol), NaN3
(16.3 mg, 0.25 mmol), CuBr (3.6 mg, 10 mol %), Cs2CO3 (81.5 mg,
d
8.18 (s,1H), 7.87 (m, 4H), 7.69 (m, 6H), 7.41 (t, 2H, J¼7.6 Hz), 7.32 (t,
1H, J¼7.2 Hz). 13C NMR (100 MHz, CDCl3)
d 142.9, 138.5, 136.1, 131.7,

K. Bolla et al. / Tetrahedron 67 (2011) 5556e5563
5563
129.0, 127.9, 127.5, 127.3, 126.6, 124.8, 119.9, 117.6, 116.2, 110.6. FT-IR
(ATR): 3097, 2962, 2924, 2853, 2222, 1604, 1499, 1455, 1396, 1228,
1095, 1022, 992, 858, 818, 799, 772, 693, 539 cmꢁ1. ESI-MS: m/z
calcd for C21H14N4 [MþH]þ 323.12, found 322.97.
159 mg, 0.5 mmol) and bromotriphenylethylene (167.6 mg, 0.5 mmol)
to give the desired product in 87% yield (202 mg, an ivory solid).
Mp¼211e213 ꢀC. 1H NMR (400 MHz, CDCl3)
d 7.75 (s, 1H), 7.47 (d, 2H,
J¼8.8 Hz), 7.28 (s, 2H), 7.14 (m, 9H), 7.08 (m, 6H), 2.97 (t, 2H, J¼7.2 Hz),
2.47 (t, 2H, J¼7.2 Hz), 2.16 (m, 2H). 13C NMR (100 MHz, CDCl3)
d 142.2,
4.3.2. 1-(40-Methoxybiphenyl-4-yl)-4-phenyl-1H-1,2,3-triazole
(3b). General procedure II was used employing potassium 4-(4-
phenyl-1H-1,2,3-triazol-1-yl)phenyltrifluoroborate (2a, 163.5 mg,
0.5 mmol) and 4-bromoanisole (93.5 mg, 0.5 mmol) to give the
desired product in 75% yield (122.7 mg, a light yellow solid).
132.6, 131.3, 131.2, 127.9, 127.8, 127.7, 126.9, 126.8, 126.7, 119.6, 24.7,
24.1, 16.4. FT-IR (ATR): 3128, 3078, 3028, 2922, 2852, 2247, 1897, 1736,
1598, 1574, 1546, 1516, 1491, 1460, 1443, 1409, 1317, 1294, 1235, 1178,
1152,1112,1073,1050,1029, 997, 978, 916, 848, 821, 762, 754, 719, 696,
626, 582, 569 cmꢁ1. ESI-MS: m/z calcd for C32H26N4 [MþH]þ 467.21,
found 467.00.
Mp¼208e213 ꢀC ꢀC. 1H NMR (400 MHz, CDCl3)
d 8.22 (s, 1H), 7.93
(d, 2H, J¼7.2 Hz), 7.84 (d, 2H, J¼8.4 Hz), 7.71 (d, 2H, J¼8.4 Hz), 7.57
(d, 2H, J¼8.8 Hz), 7.47 (t, 2H, J¼7.6 Hz), 7.38 (t, 1H, J¼7.6 Hz), 7.02 (d,
Acknowledgements
2H, J¼8.8 Hz), 3.87 (s, 3H). 13C NMR (100 MHz, CDCl3)
d 159.6, 148.4,
141.4, 135.6, 132.1, 130.2, 128.9, 128.4, 128.1, 127.8, 127.1, 125.8, 120.8,
117.4, 114.4, 55.4. FT-IR (ATR): 3119, 3094, 3062, 2959, 2922, 2922,
2839, 1736, 1608, 1574, 1505, 1480, 1454, 1441, 1417, 1400, 1293,
1281, 1256, 1228, 1181, 1095, 1073, 1040, 1019, 992, 912, 820, 759,
737, 689, 659, 606 cmꢁ1. ESI-MS: m/z calcd for C21H17N3O [MþH]þ
328.13, found 328.01.
This research was supported by the KIST Institutional Program
(2Z03470), Republic of Korea. We are grateful to Professor Gary A.
Molander (University of Pennsylvania) for friendly discussions.
Supplementary data
Supplementary data contain the copies of 1H, 13C, 19F, and 11B
NMR spectra of all new compounds. Supplementary data associated
with this article can be found in the online version at doi:10.1016/
j.tet.2011.05.126.
4.3.3. 2-(4-(4-Phenyl-1H-1,2,3-triazol-1-yl)phenyl)pyridine
(3c). General procedure II was used employing potassium 4-(4-
phenyl-1H-1,2,3-triazol-1-yl)phenyltrifluoroborate (2a, 163.5 mg,
0.5 mmol) and 2-bromopyridine (79 mg, 0.5 mmol) to give the
desired product in 65% yield (97 mg,
a
d
light brown solid).
8.76 (d, 1H, J¼4.8 Hz),
Mp¼181e188 ꢀC. 1H NMR (400 MHz, CDCl3)
References and notes
8.29 (s, 1H), 8.22 (d, 2H, J¼8.8 Hz), 7.95 (m, 4H), 7.84 (m, 2H), 7.50 (t,
2H, J¼7.2 Hz), 7.41 (t,1H, J¼7.6 Hz), 7.33 (m,1H). 13C NMR (100 MHz,
1. (a) Hartzel, L. W.; Benson, F. R. J. Am. Chem. Soc. 1954, 76, 667; (b) Genin, M. J.;
Allwine, D. A.; Anderson, D. J.; Barbachyn, M. R.; Emmert, D. E.; Garmon, S. A.;
Graber, D. R.; Grega, K. C.; Hester, J. B.; Hutchinson, D. K.; Morris, J.; Reischer, R. J.;
Ford, C. W.; Zurenko, G. E.; Hamel, J. C.; Schaadt, R. D.; Stapert, D.; Yagi, B. H. J.
Med. Chem. 2000, 43, 953; (c) Alvarez, R.; Velazquez, S.; San-Felix, A.; Aquaro, S.;
De Clercq, E.; Perno, C.-F.; Karlsson, A.; Balzarini, J.; Camarasa, M. J. J. Med. Chem.
1994, 37, 4185; (d) Pearson, W. H.; Bergmeier, S. C.; Chytra, J. A. Synthesis 1990,
156; (e) Wu, P.; Feldman, A. K.; Nugent, A. K.; Hawker, C. J.; Scheel, A.; Voit, B.;
Pyun, J.; Frechet, J. M. J.; Sharpless, K. B.; Fokin, V. V. Angew. Chem., Int. Ed. 2004,
43, 3928; (f) Li, H.; Cheng, F.; Duft, A. M.; Adronov, A. J. Am. Chem. Soc. 2005, 127,
14518; (g) Beryozkina, T.; Appukkuttan, P.; Mont, N.; Vander der Eycken, E. Org.
Lett. 2006, 8, 487.
2. (a) Huisgen, R.; Szeimies, G.; Mobius, L. Chem. Ber. 1967, 100, 2494; (b) Huisgen,
R. In 1,3-Dipolar Cycloaddition Chemistry; Padwa, A., Ed.; Wiley: New York, NY,
1984; Chapter 1, pp 1e176; (c) Huisgen, R. Pure Appl. Chem. 1989, 61, 613; (d) Gil,
M. V.; Arevalo, M. J.; Lopez, O. Synthesis 2007, 1589; (e) Rostovtsev, V. V.; Green,
L. G.; Fokin, V. V.; Sharpless, K. B. Angew. Chem., Int. Ed. 2002, 41, 2596; (f) Tornoe,
C. W.; Christensen, C.; Meldal, M. J. Org. Chem. 2002, 67, 3057.
3. (a) Molander, G. A.; Figueroa, R. Aldrichimica Acta 2005, 38, 49; (b) Stefani, H. A.;
Cella, R.; Vieira, A. S. Tetrahedron 2007, 63, 3623; (c) Molander, G. A.; Ellis, N. Acc.
Chem. Res. 2007, 40, 275; (d) Darses, S.; Genet, J.-P. Chem. Rev. 2008, 108, 288; (e)
Molander, G. A.; Canturk, B. Angew. Chem., Int. Ed. 2009, 48, 9240; (f) Molander,
G. A.; Sandrock, D. L. Curr. Opin. Drug Discovery Dev. 2009, 12, 811; (g) Doucet, H.
Eur. J. Org. Chem. 2008, 2013; (h) Darses, S.; Genet, J.-P. Eur. J. Org. Chem. 2003, 68,
4313.
4. Kim, D.-S.; Ham, J. Org. Lett. 2010, 12, 1092 and references therein.
5. Molander, G. A.; Cavalcanti, L. N.; Canturk, B. P.-S.; Kennedy, L. E. J. Org. Chem.
2009, 74, 7364.
CDCl3)
d 156.5, 155.8, 149.9, 148.5, 139.7, 137.3, 137.0, 130.4, 130.3,
130.1, 128.9, 128.5, 128.3, 127.4, 125.9, 125.8, 122.7, 122.4, 120.6,
120.5, 117.8, 117.4, 116.4. FT-IR (ATR): 3132, 3098, 3062, 2922, 2851,
2360, 1939, 1736, 1606, 1585, 1566, 1520, 1472, 1455, 1436, 1429,
1408, 1231, 1182, 1152, 1114, 1096, 1073, 1043, 1026, 990, 968, 921,
859, 809, 778, 757, 740, 721, 694, 667, 616, 569 cmꢁ1. ESI-MS: m/z
calcd for C19H14N4[MþH]þ 299.14, found 299.57.
4.3.4. 40-(4-(3-Cyanopropyl)-1H-1,2,3-triazol-1-yl)biphenyl-4-
carbonitrile (3d). General procedure II was used employing potas-
sium 4-(4-(3-cyanopropyl)-1H-1,2,3-triazol-1-yl)phenyltrifluoro-
borate (2k, 159 mg, 0.5 mmol) and 4-bromobenzonitrile (91 mg,
0.5 mmol) to give the desired product in 82% yield (128.5 mg, an
ivory solid). Mp¼122e126 ꢀC. 1H NMR (400 MHz, CDCl3)
d 7.88 (m,
3H), 7.77 (m, 6H), 3.02 (t, 2H, J¼7.2 Hz), 2.51 (t, 2H, J¼7.2 Hz), 2.19
(m, 2H). 13C NMR (100 MHz, CDCl3)
d 145.5,142.9,138.4,136.0,131.7,
127.5, 126.6, 119.8, 118.3, 118.2, 117.6, 110.6, 23.7, 23.1, 15.5. FT-IR
(ATR): 3127, 3057, 2930, 2853, 2248, 2223, 1904, 1726, 1678, 1603,
1553, 1528, 1497, 1437, 1418, 1398, 1325, 1309, 1209, 1191, 1180, 1119,
1044, 997, 988, 856, 814, 753, 720, 693, 537 cmꢁ1. ESI-MS: m/z calcd
for C19H15N5 [MþH]þ 314.13, found 313.95.
6. White, J. R.; Price, G. J.; Schiffers, S.; Raithby, P. R.; Plucinski, P. K.; Frost, C. G.
Tetrahedron Lett. 2010, 51, 3913.
7. (a) Scriven, E. F. V.; Turnbull, K. Chem. Rev. 1988, 88, 297; (b) Brase, S.; Gil, C.;
€
4.3.5. 4-(1-(4-(1,2,2-Triphenylvinyl)phenyl)-1H-1,2,3-triazol-4-yl)bu-
tanenitrile (3e). General procedure II was used employing potassium
4-(4-(3-cyanopropyl)-1H-1,2,3-triazol-1-yl)phenyltrifluoroborate (2k,
Knepper, K.; Zimmermann, V. Angew. Chem., Int. Ed. 2005, 44, 5188.
8. Cho, Y. A.; Kim, D.-S.; Ahn, H. R.; Canturk, B.; Molander, G. A.; Ham, J. Org. Lett.
2009, 11, 4330.