Palladium-Catalyzed Regioselective C-5 Arylation of 1,2,3-Triazoles with Diaryliodonium Salts

Article abstract of DOI:10.1055/s-0036-1588815

An effective method for C-5 arylation of 1,4-disubstituted 1,2,3-triazoles and C-5 regioselective arylation of 1-substituted 1,2,3-triazoles via sp ² C-H activation with palladium as a catalyst and diaryliodonium salts as arylating reagents is described. Various electron-rich and electron-deficient substituents attached to triazoles and diaryliodonium salts were tolerable to give the desired products with good isolated yields in 24 hours under air atmosphere.

Full text of DOI:10.1055/s-0036-1588815

SYNLETT
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© Georg Thieme Verlag Stuttgart · New York
2017, 28, A–F
letter
A
en
F. Gang et al.
Letter
Synlett
Palladium-Catalyzed Regioselective C-5 Arylation of 1,2,3-Tri-
azoles with Diaryliodonium Salts
Fangli Gang§
N
N
R2
Ar1
R2
N
Pd(OAc)2/(o-tolyl)3P
DMF, reflux, 24 h
N
Yang Che§
Zhengyin Du*
Hua Feng*
Ying Fu
Ar1Ar2IBF4
N
N
R1
R1
* C5-regioselective
* 1 equivalent of Ar1Ar2IBF4
* open to air
R1 = aryl, alkyl;
R2 = H, aryl
21 examples
up to 82% yield
Key Laboratory of Eco-Environment Related Polymer Materials
of Ministry of Education, College of Chemistry and Chemical
Engineering, Northwest Normal University, Lanzhou 730070,
P. R. of China
zhengyin_du@nwnu.edu.cn
clinton_du@126.com
§ These authors contributed equally to this work.
Received: 15.02.2017
Accepted after revision: 02.04.2017
Published online: 04.05.2017
N
Ph
NH2
N
N
O
N
TBSO
N
N
O
Cl
O
S
DOI: 10.1055/s-0036-1588815; Art ID: st-2017-w0112-l
OH
EtO
O
O
OTBS
Abstract An effective method for C-5 arylation of 1,4-disubstituted
1,2,3-triazoles and C-5 regioselective arylation of 1-substituted 1,2,3-
triazoles via sp2 C–H activation with palladium as a catalyst and dia-
ryliodonium salts as arylating reagents is described. Various electron-
rich and electron-deficient substituents attached to triazoles and dia-
ryliodonium salts were tolerable to give the desired products with good
isolated yields in 24 hours under air atmosphere.
antifungal
S
O
N
HIV reverse transcriptase inhibitor
N
NH
O
N
NO2
N
HN
NH2
N
N
O
CF3
O
Key words arylation, diaryliodonium salts, regioselectivity, 1,2,3-tri-
active against
potassium channel activator
azoles, C–H activation
breast, bladder, kidney cancers
Figure 1 Medical applications of 1,2,3-triazoles
1,2,3-Triazoles, as an important class of heterocyclic
compounds, have received much attention over the past de-
cades and have found wide applications in organocatalysis,1
ionic liquids2 and biological medicines (Figure 1).3 There
are two procedures available for the preparation of substi-
tuted 1,2,3-triazoles. One is the Cu-catalyzed azide-alkyne
1,3-dipolar [3+2] cycloaddition which has been fully devel-
oped.4 The other is the transition-metal-catalyzed C–H
functionalization of 1,2,3-triazoles which has gradually at-
tracted lots of interest,5 because azide-alkyne cycloaddition
reaction, in most case, needs a strong electron-withdraw-
ing group at the alkyne.6
As far as we know, transition-metal-catalyzed C–H
functionalization of 1,2,3-triazoles mainly focused on the
2-substituted 1,2,3-triazoles in which triazole was always
regarded as a directing group,7 whereas the reaction of 1-
substituted 1,2,3-triazoles reports were relatively few. In
2005, Jia and co-workers reported Cp*RuCl(PPh3)2-cata-
lyzed regioselective click reaction of organic azides and ter-
minal alkynes to produce 1,5-disubstituted 1,2,3-triazoles
(Scheme 1, a).8 Despite the remarkable progress, typically
OH
a) Fokin and Jia's work
N3
N
N
[Ru]
N
OH
+
b) Previous work
N
R2
N
N
X
N
R2
[Pd]
N
N
R1
+
R1
X = OTs, Br, I
c) This work
N
N
N
R2(H)
N
[Pd]
under air
N
N
R2(H)
Ar1Ar2IBF4
+
R1
Ar1
R1
Scheme 1 Synthesis of C-5 substituted triazoles
© Georg Thieme Verlag Stuttgart · New York — Synlett 2017, 28, A–F

B
F. Gang et al.
Letter
Synlett
methods for the regioselective synthesis of substituted
1,2,3-triazoles are still desirable. Recently, Pd-catalyzed di-
rect arylation and heteroarylation have emerged as a valu-
able alternative method used for the functionalization of
heterocycle.9 The direct arylation of 1,4-disubstituted 1,2,3-
triazoles with aryl tosylates,10 bromobenzene11 or iodoben-
zene12 as arylating reagents have also shown to be efficient
for C-5 functionalization (Scheme 1, b). In some reactions, a
solvent mixture and nitrogen atmosphere are needed. In re-
cent years, diaryliodonium salts are receiving more and
more attention as arylating reagents,13 because they have
remarkable advantages, such as high reactivity, low toxicity,
easy preparation, and no need for additional oxidizing
agent.14 However, to the best of our knowledge, no litera-
ture was exposed for C–H arylation of triazoles with dia-
ryliodonium salts as arylating reagents.
In this work, we studied the feasibility of a direct Pd-
catalyzed C-5 arylation reaction of triazoles with dia-
ryliodonium salt towards multisubstituted 1,2,3-triazoles.
It is found that C-5 arylation of 1,4-disubstituted 1,2,3-tri-
azoles and highly regioselective C-5 arylation of 1-substi-
tuted 1,2,3-triazoles proceeded smoothly in the presence of
Pd catalyst in DMF under an air atmosphere (Scheme 1, c).15
The reaction of 1-benzyl-4-phenyl-1H-1,2,3-triazole
(1a, 0.2 mmol) with diphenyliodonium tetrafluoroborate
(2a, 1 equiv) was conducted as a model reaction (Table 1).
Table 1 Optimization of the Reaction Conditionsa
N
N
BF4
N
N
N
I
cat. base
+
+
recovery of 1a
N
solvent, ligand
100 °C, 24 h
3a
1a
2a
Entry
Catalyst
Base
K2CO3
Ligand
Temp (°C)
Solvent
Conv. of 1a (%)
Yield (%)b
1
2
–
–
100
100
100
100
100
100
100
100
100
100
100
100
100
100
80
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
CH2Cl2
H2O
0
58
55
0
0
56
50
0
Pd(OAc)2
PdCl2(PPh3)2
CuI
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
t-BuOK
Cs2CO3
pyridine
Et3N
–
3
–
4
–
5
Cu NPs
–
0
0
6
PdI2
–
0
0
7
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
–
<2
<2
17
8
trace
trace
15
5
8
–
9
–
10
11
12
13
14
15
16
17
18
19
20c
21d
22e
23f
–
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
PPh3
X-Phos
20
59
84
38
59
82
55
38
27
84
85
88
0
18
55
82
36
55
78
52
35
25
80
82
83
0
(o-tolyl)3P
PCy3
(o-tolyl)3P
(o-tolyl)3P
(o-tolyl)3P
(o-tolyl)3P
(o-tolyl)3P
(o-tolyl)3P
(o-tolyl)3P
(o-tolyl)3P
(o-tolyl)3P
120
reflux
reflux
100
100
100
100
100
PhMe
DMF
DMF
DMF
DMF
a Reaction conditions: 1a (0.2 mmol), 2a (0.2 mmol), base (2 equiv), catalyst (5 mol%), ligand (10 mol%), solvent (2 mL), 24 h.
b Isolated yield based on converted 1a.
c The reaction was carried out under an Ar atmosphere.
d Amount of catalyst used was 10 mol%.
e Amount of 2a used was 0.4 mmol.
f Diphenyliodonium triflate was instead of diphenyliodonium tetrafluoroborate.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2017, 28, A–F

C
F. Gang et al.
Letter
Synlett
Screening of the reaction was first performed in DMF at 100
°C for 24 hours under catalyst- and ligand-free conditions,
but no reaction was observed when using only 2 equiva-
lents of potassium carbonate under air atmosphere (Table
1, entry 1). Then, the reaction was explored in the presence
of 5 mol% of palladium acetate under the abovementioned
conditions. It was found that 56% yield of the targeted prod-
uct 1-benzyl-4,5-diphenyl-1H-1,2,3-triazole (3a) was ob-
tained with recovery of 42% 1a (Table 1, entry 2). Based on
this finding, the effect of different transition metal catalysts
was further investigated. The use of Pd(PPh3)2Cl2 as catalyst
gave 50% of yield (Table 1, entry 3). However, when
Pd(OAc)2 was replaced by CuI, CuNPs and PdI2, no reaction
was observed and 100% of 1a were recovered (Table 1, en-
tries 4–6). Subsequently, various inorganic and organic bas-
es were also examined and the results showed that potassi-
um carbonate was the best base for this transformation (Ta-
ble 1, entries 2 and 7–10). As we know, ligands always play
an important role in the transition-metal-catalyzed organic
reactions except for a few ligand-free literature reports.16
So phosphorus ligands, such as PPh3, 2-(dicyclohexylphos-
phino)-2′,4′,6′-triisopropylbiphenyl (X-Phos), tricyclohexyl-
phosphine (PCy3) and (o-tolyl)3P, were screened and it was
found that (o-tolyl)3P ligand could give a good yield (82%) of
the product (Table 1, entry 13), whereas other ligands, such
as PPh3, PCy3 and X-Phos were less effective, and the start-
ing material 1a was not consumed completely (Table 1, en-
tries 11, 12 and 14). The temperature is another key factor
for this reaction. When the temperature was decreased to
80 °C or increased to 120 °C, the yield decreased as expect-
ed (Table 1, entries 15 and 16). The reaction was also stud-
ied in other reaction media. The results manifested that
CH2Cl2, water, and toluene were not the suitable solvents
for this reaction as 25–52% yields were obtained even un-
der reflux temperature in CH2Cl2 and in water (Table 1, en-
tries 17–19). In order to explain the necessity of air atmo-
sphere, the reaction was conducted under argon. It was
found that 80% of the product yield was achieved and no
significant decline was observed (Table 1, entry 20). There-
fore we believe that oxygen is not necessary for this reac-
tion. In addition, the amount of Pd catalyst could be in-
creased to 10 mol% (Table 1, entry 21) or the amount of 2a
could be increased to 2 equivalents (Table 1, entry 22), with
no significant change observed in the yield.
moderate yield. For example, 1-n-butyl, 1-n-hexyl and 1-n-
octyl-substituted 4-phenyl-1H-1,2,3-triazoles were con-
verted to the corresponding products 3g–i in the yield of
66%, 64% and 53%, respectively (Table 2, entries 7–9). Subse-
quently, various symmetrical and unsymmetrical dia-
ryliodonium salts were employed in the C-5 arylation of
1,4-substituted triazoles. For symmetrical di(2-fluorophe-
nyl)iodonium tetrafluoroborate (Table 2, entry 10) and
di(2-bromophenyl)iodonium tetrafluoroborate (Table 2, en-
try 11), the corresponding C-5 arylation products 3j and 3k
of 1-benzyl-4-phenyl-1H-1,2,3-triazole were obtained in
the yield of 75% and 76%, respectively. For asymmetrical di-
aryliodonium salts, competitive arylation is possible, which
is mainly determined by electronic and steric effect of the
substituent on aryl group of diaryliodonium salts. When
Ar1 was phenyl and Ar2 was 2-FC6H4 and 4-NO2C6H4 in dia-
ryliodonium salt, only C-5 phenylation products were ob-
tained in 45–71% yield (Table 2, entries 12–15). However,
when (phenyl)(2-tolyl)iodonium tetrafluoroborate as aryla-
tion reagent was treated with 1a under the same condi-
Table 2 C-5 Arylation of 1,4-Substituted 1,2,3-Triazolesa
R1
R1
N
N
N
N
N
Ar1
N
Pd(OAc)2, K2CO3
Ar1Ar2IBF4
+
(o-tolyl)3P, DMF
2
100 °C, 24 h
R2
R2
1
3
Entry
R1
R2
Ar1
Ph
Ar2
Yield (%)
1
2
Ph
H
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
3a, 82
3b, 80
3c, 78
3d, 74
3e, 67
3f, 76
3g, 66
3h, 64
3i, 53
3j, 75
3k, 76
3a, 71
3a, 62
3h, 45
3i, 59
3a, 45
4-Tol
Ph
H
Ph
3
4-Me
4-F
4-F
4-Me
H
Ph
4
Ph
Ph
5
4-FC6H4
4-FC6H4
Pr
Ph
6
Ph
7
Ph
8
C5H11
C7H15
Ph
H
Ph
9
H
Ph
10
11
12
13
14
15
16b
H
2-FC6H4
2-BrC6H4
Ph
2-FC6H4
2-BrC6H4
2-FC6H4
With these optimized conditions in hand (Table 1, entry
11), we explored the scope of this C–H bond functionaliza-
tion protocol next. To our delight, several valuable function-
al groups were tolerated in this system, which enabled the
preparation of a variety of trisubstituted triazoles in good
yields (Table 2). It was observed that the electron-with-
drawing or electron-donating groups on the benzene ring
of triazoles could be applied to yield the desired products
3b–f, and the electronic effect has little effect on the reac-
tion (Table 2, entries 2–6). When R1 was an alkyl group in-
stead of an aryl group, this transformation was achieved in
Ph
H
Ph
H
Ph
H
Ph
4-O2NC6H4
2-FC6H4
2-FC6H4
2-Tol
C5H11
C7H15
Ph
H
Ph
H
Ph
H
Ph
a Reaction condition: 1 (0.2 mmol), 2 (0.2 mmol), K2CO3 (2 equiv),
Pd(OAc)2 (5 mol%), (o-tolyl)3P (10 mol%), DMF (2 mL), 24 h. Yield is the iso-
lated yield.
b 5-Tolylation product 3l (36%) was obtained simultaneously.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2017, 28, A–F

D
F. Gang et al.
Letter
Synlett
tions, phenylation product 3a and 2-tolylation product 3l
were simultaneously obtained in 45% and 36% yield, respec-
tively (Table 2, entry 16). This may be explained by the dif-
ference between removal capacity of the differently substi-
tuted aryl in diaryliodonium salt and the ability to generate
aryl iodide.
Encouraged by these results, we further examined the
arylation reaction of 4,5-unsubstituted triazoles with dia-
ryliodonium salts under the above optimized conditions.
We were pleased to find that palladium-catalyzed coupling
reactions of various 1-substituted triazoles with diaryliodo-
nium salts proceeded smoothly to afford the highly regiose-
lective C-5 arylation products exclusively (Table 3). When
1-phenyl-1,2,3-triazole was allowed to interact with sym-
metrical diaryliodonium salt, the unique C-5 arylation
product was obtained in moderate yield (Table 3, entries 1
and 2). However, when a bromo group was attached on the
benzene ring of 1-phenyl-1,2,3-triazole, a manifest de-
crease of product yield was observed (Table 3, entry 5). Un-
symmetrical diaryliodonium salts bearing functional group
such as fluoro and methyl afforded a mixture of C-5 aryla-
tion triazoles regioselectively in good total yield of 72% and
75%, respectively (Table 3, entries 3 and 4). From these re-
sults we can see that the arylation reactivity of phenyl is
close to the arylation reactivities of 2-fluorophenyl and 4-
methylphenyl in this reaction to result in a mixture of C5-
arylation products.
Table 3 C-5 Regioselective Arylation of 1-Substituted Triazolesa
R3
R3
Pd(OAc)2, K2CO3
Ar1(Ar2)
Ar1Ar2IBF4
+
N
N
(o-tolyl)3P, DMF
100 °C, 24 h
2
N
N
N
N
1
3
Entry
1
R3
Ar1Ar2IBF4
Product yield (%)
BF4
I
H
N
N
N
3m, 67
BF4
I
F
F
2
3
4
H
H
H
N
N
F
N
3n, 61
BF4
I
F
N
N
N
N
N
N
F
N
3m, 40; 3n, 32
BF4
I
N
N
N
N
N
3m, 33; 3o, 42
Br
BF4
I
5
4-Br
N
N
N
3p, 42
a Reaction conditions: 1 (0.2 mmol), 2 (0.2 mmol), K2CO3 (2 equiv), Pd(OAc)2 (5 mol%), (o-tolyl)3P (10 mol%), DMF (2 mL), 24 h. Isolated yields are reported.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2017, 28, A–F

E
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According to a previous Gevorgyan’s report, DFT calcu-
lations show negative charge at C-5 while positive charge at
C-4 of N-methyl-1H-1,2,3-triazole.11a So we calculated
charges at C-4 and C-5 of N-phenyl-1H-1,2,3-triazole using
the same method. The results show substantial negative
charge at C-5 while positive charge at C-4 position (for de-
tails, see the supporting information). Therefore we have
the reason to believe that C-5 arylation of 1,4-disubstituted
and 1-monosubstituted 1,2,3-triazoles is also based on neg-
ative charge of C-5 and is an electrophilic mechanism.
Funding Information
National Natural Science Foundation of China (21262028)
Natural Science Foundation of Gansu Province (1208RJZA140)
Supporting Information
Supporting information for this article is available online at
https://doi.org/10.1055/s-0036-1588815.
S
u
p
p
o
nrtogI
f
rmoaitn
S
u
p
p
ortiInfogrmoaitn
Based on the above facts and previous literatures,7c,11a,12a
a
References and Notes
proposed mechanism to rationalize this transformation is
shown in Scheme 2. First, Pd(0) is formed by the reduction
of palladium acetate in the presence of phosphorus ligand,
which is further transformed into aryl Pd(II) complex A by
oxidative addition with diaryliodonium salt. Subsequently,
electrophilic addition is initiated between complex A and
substrate triazoles to generate C5-metalation transition
state B, then hydrogen is removed under base to form C5-
metalation triazole intermediate C. The reductive elimina-
tion of intermediate C gives the coupling product and re-
generates Pd0 which is further oxidized by diaryliodonium
salts into Pd(II) complex A to participate in the next cycle.
(1) (a) Yan, Z. Y.; Niu, Y. N.; Wei, H. L. Tetrahedron: Asymmetry
2006, 17, 3288. (b) Zammit, C. M.; Wills, M. Tetrahedron: Asym-
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(2) Yoshida, Y.; Takizawa, S.; Sasai, H. Tetrahedron: Asymmetry
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Rev. 2007, 36, 1249. (c) Lutz, J. F. Angew. Chem. Int. Ed. 2007, 46,
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2002, 67, 3057. (e) Rostovtsev, V. V.; Green, L. G.; Fokin, V. V.;
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C.; Finn, M. G.; Sharpless, K. B. Angew. Chem. Int. Ed. 2001, 40,
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Adv. Synth. Catal. 2005, 347, 811. (h) Himo, F.; Lovell, T.; Hilgraf,
R.; Rostovtsev, V. V.; Noodles, L.; Sharpless, K. B.; Fokin, V. V.
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Finn, M. G. Angew. Chem. Int. Ed. 2005, 44, 2210.
N
N
R1
N
Ar2I
Ar1PdIILn
R2(H)
Ar1Ar2IBF4
Ln
A
(5) (a) Gang, F.; Xu, G.; Dong, T.; Yang, L.; Du, Z. Chin. J. Org. Chem.
2015, 35, 1428. (b) Yan, G. B.; Borah, A. J.; Yang, M. H. Adv. Synth.
Catal. 2014, 356, 2375. (c) Tian, Q.; Ping, H.; Kuang, C. Org.
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M.; Ryu, J. S. Bioorg. Med. Chem. Lett. 2013, 23, 1083.
Ln
N
H
Pd0
N
R2(H)
Pd(OAc)2
N
H
Ar1
R1
Pd
Ln
N
R2(H)
N
B
N
N
Ar1
N
R2(H)
Ar1
K2CO3
R1
N
(6) Fan, W.-Q.; Katritzky, A. R. Comprehensive Heterocyclic Chemis-
R1
KHCO3
LnPd
try II;4Vo.
l
Katritzky, A. R.; Rees, C. W.; Scriven, E. F. V., Eds.; Elsevier:
C
Amsterdam, 1996, 1.
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Scheme 2 Proposed mechanism [L = (o-tolyl)3P]
In summary, we have successfully developed a Pd-cata-
lyzed C-5 arylation of 1,2,3-triazoles via sp2 C–H activation
with diaryliodonium salts as arylating reagents. When 1-
substituted 1,2,3-triazoles were used as substrates, the
highly regioselective C-5 arylation to afford 1,5-disubstitut-
ed 1,2,3-triazoles was realized efficiently. This method
shows good tolerance for various electron-rich and elec-
tron-deficient substitutions and moderate to good yields
are obtained. Compared with the use of multiple equiva-
lents of diaryliodonium salts in most of previous literatures,
only one equivalent of diaryliodonium salt was needed in
this reaction. The possible mechanism is also proposed.
(11) (a) Chuprakov, S.; Chernyak, N.; Dudnik, A. S.; Gevorgyan, V.
Org. Lett. 2007, 9, 2333. (b) Lesieur, M.; Lazreq, F.; Cazin, C. S. J.
Chem. Commun. 2014, 50, 8927. (c) Ackermann, L.; Vicente, R.
Org. Lett. 2009, 11, 4922.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2017, 28, A–F

F
F. Gang et al.
Letter
Synlett
(12) (a) Yamajala, K. D. B.; Patil, M.; Banerjee, S. J. Org. Chem. 2015,
80, 3003. (b) Ackermann, L.; Potukuchi, H. K.; Lansberg, D.;
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7.37 (t, J = 7.4 Hz, 2 H), 7.19 (s, 1 H), 7.06 (d, J = 7.2 Hz, 2 H),
6.90–6.97 (m, 2 H), 6.87 (q, J = 8.0 Hz, 3 H), 5.30 (s, 2 H). 13C
NMR (151 MHz, CDCl3): δ = 162.4 (d, JC–F = 227.8 Hz), 143.8,
133.5, 130.9 (d, JC–F = 3.6 Hz), 129.9, 129.5, 129.4, 129.3, 128.4
(d, JC–F = 8.1 Hz), 127.6, 115.7 (d, JC–F = 21.6 Hz), 51.4. HRMS (ESI,
MeOH): m/z [M + H]+ calcd for C21H16F2N3: 348.1307; found:
348.1315. IR (KBr): 3032, 2921, 2853, 1512, 1224, 843, 766, 705
(13) (a) Merritt, E. A.; Olofsson, B. Angew. Chem. Int. Ed. 2009, 48,
9052. (b) Zhdankin, V. V.; Stang, P. J. Chem. Rev. 2008, 108, 5299.
(c) Deprez, N. R.; Sanford, M. S. Inorg. Chem. 2007, 46, 1924.
(d) Malmgren, J.; Nagendiran, A.; Tai, C. W.; Backvall, J. E.;
Olofsson, B. Chem. Eur. J. 2014, 20, 13531. (e) Modha, S. G.;
Greaney, M. F. J. Am. Chem. Soc. 2015, 137, 1416. (f) Zhu, Y.;
Bauer, M.; Ackermann, L. Chem. Eur. J. 2015, 21, 9980. (g) Hu, B.;
Miller, W. H.; Neumann, K. D.; Linstad, E. J.; DiMagno, S. G.
Chem. Eur. J. 2015, 21, 6394. (h) Zhu, Y.; Bauer, M.; Ploog, J.;
Ackermann, L. Chem. Eur. J. 2014, 20, 13099. (i) Yang, P.; Wang,
R.; Wu, H.; Du, Z.; Fu, Y. Asian J. Org. Chem. 2017, 6, 184.
(14) (a) Bielawski, M.; Aili, D.; Olofsson, B. J. Org. Chem. 2008, 73,
4602. (b) Bielawski, M.; Zhu, M.; Olofssona, B. Adv. Synth. Catal.
2007, 349, 2610.
(15) General Procedure for Regioselective C-5 Arylation of 1,2,3-
Triazoles: To a dried flask were added 1,2,3-triazoles (0.2
mmol), diaryliodonium salt (0.2 mmol), K2CO3 (2.0 equiv),
Pd(OAc)2 (5 mol %), tris(o-tolyl)phosphine (10 mol%), and DMF
(2 mL). Then the reaction mixture was stirred in an oil bath and
heated slowly to 100 °C for 24 h. The reaction was monitored by
TLC until no change was observed. The solution was cooled to
r.t., and then diluted with EtOAc (10 mL). The organic phase was
washed with brine (3 × 10 mL), dried over anhyd Na2SO4 and
concentrated under vacuum to get the crude product. The crude
product was further purified by column chromatography with
hexane–EtOAc as eluent and the pure product was obtained.
Diaryliodonium salts were prepared in accordance with the
method previously reported by Olofsson’s group.14a 1,4-Disub-
stituted 1,2,3-triazoles were prepared according to our previous
work.16a 1-Substituted 1,2,3-triazoles were prepared according
to the previous literature.17 The analytical data of new com-
pounds are as follows.
cm–1
.
1-(4-Fluorobenzyl)-5-phenyl-4-(4-tolyl)-1H-1,2,3-triazole
(3f): white solid; yield: 52.1 mg (76%); mp 147–150 °C. 1H NMR
(600 MHz, CDCl3): δ = 7.48–7.53 (m, 3 H), 7.43 (t, J = 7.5 Hz, 2
H), 7.15 (d, J = 7.3 Hz, 2 H), 7.06 (d, J = 7.8 Hz, 2 H), 6.92–6.99 (m,
4 H), 5.36 (s, 2 H), 2.30 (s, 3 H). 13C NMR (151 MHz, CDCl3): δ =
161.5 (d, JC–F = 247.1 Hz), 143.7, 137.9, 133.6, 132.3, 130.1,
129.7, 129.3, 129.2, 128.4 (d, JC–F = 8.1 Hz), 127.7, 127.5, 127.1
(d, JC–F = 3.1 Hz), 115.3 (d, JC–F = 21.5 Hz), 51.9, 21.1. HRMS (ESI,
MeOH): m/z [M + H]+ calcd for C22H19FN3: 344.1558; found:
344.1564. IR (KBr): 3034, 2924, 2854, 1514, 1354, 1216, 839,
746, 696 cm–1
.
1-Benzyl-5-(2-bromophenyl)-4-phenyl-1H-1,2,3-triazole
(3k): pale yellow solid; yield: 59.3 mg (76%); mp 99–101 °C. 1H
NMR (600 MHz, CDCl3): δ = 7.54 (d, J = 7.0 Hz, 2 H), 7.47 (d, J =
7.1 Hz, 1 H), 7.42 (t, J = 7.4 Hz, 2 H), 7.30 (d, J = 8.7 Hz, 1 H), 7.24
(s, 3 H), 7.15 (d, J = 7.2 Hz, 2 H), 7.03 (d, J = 4.6 Hz, 2 H), 6.79 (d,
J = 8.7 Hz, 1 H), 5.41 (s, 2 H). 13C NMR (151 MHz, CDCl3): δ =
155.5, 144.5, 135.2, 133.9, 132.3, 130.7, 130.5, 130.1, 129.7,
129.2, 128.5, 128.2, 127.8, 127.5, 126.8, 117.4, 52.1. HRMS (ESI,
MeOH): m/z [M + H]+ calcd for C21H17BrN3: 390.0601; found:
390.0609. IR (KBr): 3061, 2925, 2855, 1344, 763, 734, 695, 601
cm–1
.
(16) (a) Huang, L.; Liu, W.; Wu, J.; Fu, Y.; Wang, K.; Huo, C.; Du, Z. Tet-
rahedron Lett. 2014, 55, 2312. (b) Gang, F.; Dong, T.; Xu, G.; Fu,
Y.; Du, Z. Heterocycles 2015, 91, 1964. (c) Xu, G.; Zhang, Y.;
Wang, K.; Fu, Y.; Du, Z. J. Chem. Res. 2015, 39, 399. (d) Zhang, X.;
Zhang, W.; Ren, X.; Zhang, L.; Lu, X. Org. Lett. 2011, 13, 2402.
(e) Ranu, B. C.; Saha, A.; Jana, R. Adv. Synth. Catal. 2007, 349,
2690.
1-(4-Fluorobenzyl)-4-(4-fluorophenyl)-5-phenyl-1H-1,2,3-
triazole (3e): white solid; yield: 46.5 mg (67%); mp 112–115 °C.
1H NMR (600 MHz, CDCl3): δ = 7.44 (dd, J = 13.8, 6.5 Hz, 3 H),
(17) Kolarovic, C. A.; Schnürch, M.; Mihovilovic, M. D. J. Org. Chem.
2011, 76, 2613.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2017, 28, A–F