A Copper(I)-Mediated Tandem Three-Component Synthesis of 5-Allyl-1,2,3-triazoles

Article abstract of DOI:10.1055/s-0039-1691506

A copper(I)-mediated tandem three-component reaction using alkynes, azides, allyl iodides, CuI and NaNH ₂ is developed. The reactions proceed smoothly at room temperature to afford 5-allyl-1,2,3-triazoles, which can be further converted into 1,2,3-triazole-fused tricyclic scaffolds. This method features an efficient one-pot cascade route using commercial alkynes and affords the corresponding 5-allyl-1,2,3-triazoles with high yields and good selectivity under mild reaction conditions.

Full text of DOI:10.1055/s-0039-1691506

SYNTHESIS
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© Georg Thieme Verlag Stuttgart · New York
2019, 51, A–K
paper
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en
Y. Song et al.
Paper
Synthesis
A Copper(I)-Mediated Tandem Three-Component Synthesis of
5-Allyl-1,2,3-triazoles
Yoona Song‡
Soyun Lee‡
CuI, NaNH2
toluene, rt
Further
modification
R2
Palash Dutta
N
N
N
N
R1
H
R1
+
N3 R2
R1
Jae-Sang Ryu*
0
0
0
0-
0
0
0
3-0
8
0
2-6
3
9
8
N
N
I
College of Pharmacy & Graduate School of Pharmaceutical
Sciences, Ewha Womans University, 52 Ewhayeodae-gil,
Seodaemun-Gu, Seoul 03760, Republic of Korea
ryuj@ewha.ac.kr
polycyclic scaffolds
(37−92%)
• One-pot three-component reaction
• Commercial alkynes can be used
‡ These authors contributed equally to this work.
Received: 18.09.2019
Accepted after revision: 13.11.2019
Published online: 25.11.2019
tential. In comparison with step-by-step procedures, well-
established MCRs provide a more direct and robust ap-
proach for the highly efficient synthesis of 1,4,5-trisubsti-
tuted 1,2,3-triazoles.10
DOI: 10.1055/s-0039-1691506; Art ID: ss-2019-m0538-op
Abstract A copper(I)-mediated tandem three-component reaction us-
ing alkynes, azides, allyl iodides, CuI and NaNH2 is developed. The reac-
tions proceed smoothly at room temperature to afford 5-allyl-1,2,3-tri-
azoles, which can be further converted into 1,2,3-triazole-fused tricyclic
scaffolds. This method features an efficient one-pot cascade route us-
ing commercial alkynes and affords the corresponding 5-allyl-1,2,3-tri-
azoles with high yields and good selectivity under mild reaction condi-
tions.
1,2,3-Triazole is an important scaffold.11 Although 1,2,3-
triazoles do not occur in nature, synthetic 1,2,3-triazoles
exert a variety of biological activities and have attracted the
attention of medicinal chemists in the field of drug discov-
ery. At present, 1,2,3-triazole-containing pharmaceuticals
such as rufinamide12 and tazobactam13 are readily available,
and several 1,2,3-triazole-based drug candidates are being
evaluated in clinical trials.14 In addition, 1,2,3-triazoles are
also ubiquitous in functional materials. They are used in
various fields including bioconjugation15 and materials sci-
ence.16 In particular, a facile synthetic protocol known as
Cu(I)-catalyzed azide–alkyne cycloaddition (CuAAC)17 has
contributed to the broad application of 1,2,3-triazoles.
However, CuAAC is limited to terminal alkyne substrates,
which are not suitable for the synthesis of fully substituted
1,2,3-triazoles.
Key words 1,2,3-triazoles, multicomponent reactions, one-pot reac-
tions, click reactions, copper catalyst
One-pot multicomponent reactions (MCRs)1 are defined
as reactions in which three or more components are mixed
in a single reaction vessel at the same time, forming com-
plex final products containing most of the atoms of the
starting materials. MCRs include one or more sequential
chemical transformations without changing the reaction
medium after each reaction. MCRs can be used to quickly
generate large molecular diversity and to easily develop
chemical libraries, which usually require more time and ef-
fort to produce through stepwise protocols.2 Therefore, they
are particularly attractive in both the diversity-oriented
synthesis of drug-like molecules3 and the construction of
large-scale bioactive compound libraries in the pharmaceu-
tical industry.
We are particularly interested in 5-allyl-1,2,3-triazoles18
as precursors for the development of conformationally rigid
polycyclic heterocycles. However, reports of efficient MCR
protocols for the synthesis of 5-allyl-1,2,3-triazoles are rare.
Although we previously reported a one-pot process to pro-
duce 5-allyl-1,2,3-triazoles using 1-copper(I)-alkynes,19
they are not commercially available, and their synthesis and
purification is tedious. The direct use of commercial
alkynes for the synthesis of 5-allyl-1,2,3-triazoles is more
efficient and is encouraged. Herein, we report one-pot,
three-component reactions for the synthesis of 5-allyl-
1,2,3-triazoles directly using commercial alkynes along
with optimization of the reaction conditions.
Since the first MCR (the Strecker reaction4) was intro-
duced, the area of MCRs has grown tremendously, provid-
ing new reactions and strategies. In particular, a consider-
able number of MCRs have focused on generating unique
small heterocyclic molecules such as tetrazoles,5 indoles,6
pyrroles,7 imidazo[1,2-]pyridines,8 and triazoles.9 The use
of MCRs to construct fully functionalized 1,2,3-triazole li-
braries from readily available building blocks has great po-
To develop a tandem three-component CuAAC–allylation
reaction,20 we began by investigating one-pot, three-com-
ponent reactions with 4-ethynylanisole (1a), 1.2 equivalents
© 2019. Thieme. All rights reserved. Synthesis 2019, 51, A–K
Georg Thieme Verlag KG, Rüdigerstraße 14, 70469 Stuttgart, Germany

B
Y. Song et al.
Paper
Synthesis
of CuI, 1.5 equivalents of benzyl azide (2a), 4 equivalents of
allyl iodide, and 2 equivalents of base (Table 1). In the pre-
liminary screening of reaction conditions, we initially used
Et3N as the base, which is frequently used in conventional
click reactions. The reaction was heterogeneous and slug-
gish. After 74 hours at room temperature, we obtained the
desired product, 5-allyl-1,2,3-triazole 4a, along with an
enyne byproduct 3a and a protonation byproduct 5a (8%,
8%, and 9% yield, respectively) (entry 1). The use of Et3N ap-
peared to be ineffective because only a small amount of the
desired product 4a was formed. Therefore, we decided to
screen a series of bases (Et3N, NaOH, KOt-Bu, and NaNH2).
When NaOH was used as the base in toluene, the reaction
was heterogeneous and sluggish, forming an aggregated
mass in toluene. After 48 hours, the starting alkyne 1a was
almost consumed, and 44% of 4a, 16% of 3a, and 4% of 5a
were isolated (entry 2).
At this stage, we scrutinized a plausible mechanism, as
shown in Scheme 1, based on previous mechanistic stud-
ies21 and our observations. We hypothesized that the reac-
tion begins with the formation of Cu(I) acetylide species I-2
via the  complex I-1. Coordination of copper to the alkyne
C≡C lowers the pKa of the alkyne C–H bond by up to 9.8 pH
units, which allows proton abstraction with a weak base.
The resulting Cu(I) acetylide I-2 coordinates with the azide
2a to form the intermediate I-4, with subsequent cycliza-
tion leading to the formation of the metallocycle intermedi-
ate I-5. The six-membered Cu(I)-intermediate contracts to
the Cu(I)-1,2,3-triazole intermediate I-6, which is readily
trapped by allyl iodide to yield the desired 5-allyl-1,2,3-tri-
azole 4a. This mechanism could be complicated by the bi-
metallic mechanism of the CuAAC.21
In a conventional click reaction without any trapping
electrophile, I-6 would capture the proton from the proton-
ated base (the conjugate acid) such as Et3N+H (H–Base).
Therefore, if stronger bases were used, the proton from the
weaker conjugate acid would not be readily available. The
capture of a proton by I-6 from a weaker conjugate acid
might be difficult, decreasing the chance of protonolysis of
I-6. Indeed, when stronger bases were used, the formation
of 5a was effectively reduced (~9% for Et3N vs ~4% for NaOH,
~5% for KOt-Bu and ~2% for NaNH2) (Table 1, entries 1–4). A
marked change was observed with NaNH2, with 81% of 4a
and 2% of 5a being isolated (entry 4). However, the forma-
tion of 3a could not be avoided.
Table 1 Optimization of the Reaction Conditionsa
MeO
3a
MeO
H
CuI, base
solvent, rt
1a
N
N
MeO
+
N
I
N3
4a
2a
H
Next, we investigated the effect of solvents on the yield
of the CuAAC–allylation reactions in the presence of NaNH2.
The reactions were conducted in various solvents including
CH2Cl2, THF, and MeCN (Table 1, entries 5–7). Considering
the yield of the product, toluene (entry 4) was the best sol-
vent for the reaction.
N
N
MeO
N
5a
Entry
Base
Solvent
Time (h)
Yield (%)b
3a
4a
5a
According to the proposed mechanism, the formation of
compounds 3a and 4a is dependent on the concentrations
of I-2 and I-6 and compete with each other. In the absence
of a trapping electrophile such as allyl iodide, I-2 would be
converted into I-6 without the formation of 3a. Therefore,
allyl iodide was added to the mixture after the pre-mixing
of the alkyne, CuI, azide, and base for 2 hours to allow suffi-
cient time for the formation of I-6. Interestingly, the de-
layed addition of allyl iodide greatly decreased the forma-
tion of 3a (0%); however, a considerable amount of the hy-
dration byproduct 5a (29%) was isolated (Table 1, entry 8).
It is possible that the delayed addition of allyl iodide in-
creases the chance of protonolysis of I-6 in the absence of a
trapping electrophile. The use of molecular sieves as an ad-
ditive did not completely suppress protonolysis; however, a
decreased amount of the hydration byproduct 5a (14%) was
isolated (entry 9). In addition, it would be very interesting
to determine whether this reaction proceeded catalytically
or not. When 10 mol% of CuI was employed, only 20% of all-
yltriazole 4a was isolated along with 36% of 3a and 3% of 5a
1
Et3N
toluene
toluene
toluene
toluene
CH2Cl2
THF
74
48
0.5
1
8
8
9
4
5
2
1
5
9
2
NaOH
16
44
30
81
47
69
39
68
69
20
3
KOt-Bu
NaNH2
NaNH2
NaNH2
NaNH2
NaNH2
NaNH2
NaNH2
17
15
24
17
30
0
4
5
1
6
1
7
MeCN
0.5
0.5
2
8c
9c,d
10e
toluene
toluene
toluene
29
2
14
3
48
36
a Reaction conditions: 1a (65.8 mg, 0.4 mmol), 2a (94.9 mg, 0.6 mmol),
CuI (91.4 mg, 0.48 mmol), base (0.8 mmol), allyl iodide (146 L, 1.6
mmol), solvent (1 mL), Ar atmosphere.
b Yield of isolated products.
c Allyl iodide was added to the mixture after pre-mixing of the alkyne, CuI,
the azide and the base for 2 h.
d Molecular sieves (5 Å) were used.
e A catalytic amount of CuI (10 mol%) was used.
© 2019. Thieme. All rights reserved. Synthesis 2019, 51, A–K

C
Y. Song et al.
Paper
Synthesis
R1
R1
CuLn–1
3a
I–3
I
I– + CuLn
I
CuLn
B
N
CuLn
N
R2
R1
H
N
R1
H
R1
CuLn
2a
I–1
I–2
1a
+H
B
R
1 = 4-methoxyphenyl
R1
CuLn–1
R2 = benzyl
B = base
N
N
R2
N
I–4
I
CuLn–1
LnCu
R1
•
R2
R2
CuLn–1
N
N
N
R1
R1
N
N
N
N
N
N
R2
I–7
I–6
I–5
I
+H
B
CuLn
B + CuLn
I– + CuLn
H
R2
R2
N
N
N
R1
R1
N
N
N
4a
5a
Scheme 1 A plausible mechanism for the Cu(I)-mediated tandem three-component reaction
(entry 10). Hence, the reaction was not effective catalytical-
ly. Based on the results in Table 1, we chose NaNH2 as the
base and the relatively non-polar solvent toluene for further
studies.
tivity with respect to the protonation byproducts 5k–m.
The reaction was also compatible with aliphatic alkynes 1n
and 1o, and protonation byproducts 5n and 5o were not
detected. In addition, reactions with several azides were
evaluated. In these cases, the desired allyl products 4p–s
were obtained with moderate to good yields (37–76%).
Finally, we examined the synthetic utility of the 5-allyl-
1,2,3-triazoles as versatile building blocks. As an example,
the alkene-tethered 5-allyl-1,2,3-triazole 4t was synthe-
sized via the tandem three-component CuAAC–allylation
and was subsequently converted into the fused tricyclic
1,2,3-triazole 6t through a Pd-catalyzed Heck reaction
(Scheme 3).
In conclusion, we have developed a novel Cu(I)-mediat-
ed tandem three-component reaction using alkynes, azides,
allyl iodide, CuI, and NaNH2. The 5-allyl-1,2,3-triazoles
were produced via a 1,3-dipolar cycloaddition followed by
in situ trapping of the C(sp2)–Cu intermediate. The forma-
tion of the hydration byproduct 5 was efficiently sup-
pressed. The present method and the method using 1-cop-
per(I)-alkynes are complementary in the synthesis of 5-al-
lyl-1,4-disubstituted 1,2,3-triazoles, which can be further
Once optimized conditions had been established for the
tandem three-component CuAAC–allylation, the scope of
the reaction was investigated (Scheme 2). We initially stud-
ied the tandem reaction with different commercial alkynes.
All the reactions using various alkynes efficiently led to the
formation of 5-allyl-1,2,3-triazoles 4 and enyne byproducts
3 in toluene at room temperature, with the formation of
protonation byproducts 5 being suppressed effectively. In-
terestingly, the reaction yields and selectivities were de-
pendent on the electronic nature of the alkynes; arylal-
kynes 1b–f bearing electron-donating substituents and
arylalkynes 1g–j bearing fluoro, difluoro, and trifluoro-
methyl substituents underwent the one-pot three-compo-
nent reactions smoothly to provide the corresponding 5-al-
lyl-1,2,3-triazoles 4b–j at room temperature with moderate
to excellent yields (63–92%). However, arylalkynes 1k–m
bearing strong electron-withdrawing substituents such as
nitro, nitrile, and bistrifluoromethyl exhibited poor selec-
© 2019. Thieme. All rights reserved. Synthesis 2019, 51, A–K

D
Y. Song et al.
Paper
Synthesis
H
R2
R2
I
N
N
N
N
R1
H
+
N3 R2
R1
R1
R1
CuI, NaNH2
toluene, rt
N
N
1
2
3
4
5
N
N
N
N
N
n-C5H11
N
N
N
N
4b, 0.5 h
(3b 6%; 4b 74%; 5b 0%)
4c, 1 h
(3c 13%; 4c 84%; 5c 0%)
4d, 5 h
(3d 4%; 4d 77%; 5d 5%)
MeO
MeO
N
N
N
N
F
N
N
N
N
N
MeO
4e, 3 h
4f, 2 h
4g, 1 h
(3e 15%; 4e 75%; 5e 5%)
(3f 11%; 4f 81%; 5f 6%)
(3g 8%; 4g 88%; 5g 0%)
F
F
F
N
N
N
F3C
N
N
N
N
N
N
4h, 6 h
4i, 24 h
4j, 1 h
(3h 0%; 4h 63%; 5h 10%)
(3i 7%; 4i 72%; 5i 10%)
(3j 0%; 4j 92%; 5j 4%)
F3C
F3C
N
N
N
O2N
NC
N
N
N
N
N
N
4k, 5 h
4l, 3 h
4m, 2 h
(3k 6%; 4k 53%; 5k 31%)
(3l 7%; 4l 69%; 5l 24%)
(3m 0%; 4m 59%; 5m 24%)
N
N
N
N
N
N
N
N
N
CN
4n, 24 h
4o, 2 h
4p, 6 h
(3n 0%; 4n 64%; 5n 0%)
(3o 8%; 4o 71%; 5o 0%)
(3p 0%; 4p 53%; 5p 6%)
N
N
N
MeO
F3C
CN
N
Br
N
N
N
N
N
CN
4q, 24 h
(3q 13%; 4q 37%; 5q 3%)
4r, 22 h
(3r 16%; 4r 58%; 5r 10%)
4s, 7 h
(3s 10%; 4s 76%; 5s 13%)
Scheme 2 Reaction scope. Reagents and conditions: 1 (0.4 mmol), 2 (0.6 mmol), CuI (91.4 mg, 0.48 mmol), NaNH2 (31.2 mg, 0.8 mmol), allyl iodide
(146 L, 1.6 mmol), toluene (1 mL), Ar atmosphere.
transformed into beneficial fused heterocycles. This domi-
no reaction is notable for its mild conditions and high effi-
ciency.
tions were transferred via syringe or stainless-steel cannula. TLC was
performed on 0.25 mm E. Merck silica gel 60 F254 plates and samples
were visualized under UV light (254 nm) or by staining with cerium
ammonium molybdate (CAM), potassium permanganate (KMnO4) or
p-anisaldehyde. Flash chromatography was performed on E. Merck
silica gel 60 (230–400 mesh). Reagents were purchased from com-
mercial suppliers and were used without further purification unless
otherwise noted. Solvents were distilled from appropriate drying
agents (CaH2 or Na wire) under an Ar atmosphere at 760 mmHg. NMR
All reactions were performed in oven-dried glassware fitted with
glass stoppers under a positive pressure of Ar with magnetic stirring,
unless otherwise noted. Air- and moisture-sensitive liquids and solu-
© 2019. Thieme. All rights reserved. Synthesis 2019, 51, A–K

E
Y. Song et al.
Paper
Synthesis
13C NMR (100 MHz, CDCl3):  = 159.4, 145.7, 135.1, 132.4, 129.6,
Br
129.0, 128.5, 128.3, 127.2, 123.9, 117.6, 114.1, 55.3, 52.0, 27.0.
Br
HRMS (ESI): m/z [M + H]+ calcd for C19H20N3O: 306.1601; found:
306.1600.
N3
NaNH2, CuI
N
MeO
MeO
N
I
N
1-Benzyl-4-(4-methoxyphenyl)-1H-1,2,3-triazole (5a)
1a
4t
toluene, rt
34 h, 43%
Yield: 1.7 mg (2%); white solid; mp 141.7–143.7 °C; Rf = 0.20 (hex-
ane/EtOAc, 3:1).
1H NMR (400 MHz, CDCl3):  = 7.72 (d, J = 8.8 Hz, 2 H), 7.57 (s, 1 H),
7.43–7.28 (m, 5 H), 6.93 (d, J = 8.8 Hz, 2 H), 5.57 (s, 2 H), 3.83 (s, 3 H).
Pd(OAc)2, n-Bu4N+Cl–
KOAc, toluene, 110 °C
40 min, 59%
13C NMR (100 MHz, CDCl3):  = 159.8, 148.3, 135.0, 129.3, 128.9,
128.3, 127.2, 123.5, 118.9, 114.4, 55.5, 54.4.
HRMS (ESI): m/z [M + Na]+ calcd for C16H15N3ONa: 288.1107; found:
288.1106.
N
MeO
N
N
6t
Pent-4-en-1-yn-1-ylbenzene (3b)
Scheme 3 Synthesis of a fused 1,2,3-triazole via the Cu(I)-mediated
azide–alkyne cycloaddition–allylation reaction and a subsequent Pd-
catalyzed Heck reaction
Yield: 3.5 mg (6%); pale yellow liquid; Rf = 0.88 (hexane/EtOAc, 2:1).
1H NMR (400 MHz, CDCl3):  = 7.45–7.37 (m, 2 H), 7.30–7.21 (m, 3 H),
5.87 (ddt, J = 16.8, 10.0, 5.2 Hz, 1 H), 5.40 (dq, J = 16.8, 1.6 Hz, 1 H),
5.15 (dq, J = 10.0, 1.6 Hz, 1 H), 3.16 (dt, J = 5.2, 1.6 Hz, 2 H).
13C NMR (100 MHz, CDCl3):  = 132.5, 131.6, 128.3, 127.8, 123.8,
116.3, 86.6, 83.0, 23.8.
spectra were recorded at 24 °C. Chemical shifts are expressed in ppm
relative to TMS (1H, 0 ppm), CDCl3 (1H, 7.26 ppm; 13C, 77.2 ppm); cou-
pling constants are expressed in Hz. High-resolution mass spectros-
copy (HRMS) was performed by electrospray ionization (ESI, TOF),
electron ionization (EI, magnetic sector), or fast atom bombardment
(FAB, magnetic sector).
HRMS (EI): m/z [M]+ calcd for C11H10: 142.0783; found: 142.0781.
5-Allyl-1-benzyl-4-phenyl-1H-1,2,3-triazole (4b)
Yield: 81.3 mg (74%); yellow oil; Rf = 0.15 (hexane/EtOAc, 6:1).
5-Allyl-1,2,3-triazoles 4a–s; Typical Procedure
1H NMR (400 MHz, CDCl3):  = 7.68 (d, J = 8.0 Hz, 2 H), 7.43 (t, J = 8.0
Hz, 2 H), 7.39–7.28 (m, 4 H), 7.19 (d, J = 8.0 Hz, 2 H), 5.83 (ddt,
J = 17.2, 10.0, 5.2 Hz, 1 H), 5.55 (s, 2 H), 5.16 (dq, J = 10.0, 2.0 Hz, 1 H),
4.93 (dq, J = 17.2, 2.0 Hz, 1 H), 3.45 (dt, J = 5.6, 2.0 Hz, 2 H).
13C NMR (100 MHz, CDCl3):  = 145.9, 135.1, 132.3, 131.4, 130.4,
129.1, 128.8, 128.4, 128.0, 127.3, 127.2, 117.8, 52.1, 27.1.
To an oven-dried round-bottom flask with a side arm were added CuI
(91.4 mg, 480 mol) and NaNH2 (31.2 mg, 800 mol). A solution of 4-
methoxyphenylacetylene (1a) (52.9 mg, 400 mol), benzyl azide (2a)
(75.0 L, 600 mol) and allyl iodide (146 L, 1.60 mmol) in anhydrous
toluene (1 mL) was added. The heterogeneous reaction mixture was
stirred at room temperature for 1 h. Upon completion of the reaction,
the mixture was filtered through a plug of Celite and rinsed with
CH2Cl2 (50 mL). The filtrate was concentrated and purified by column
chromatography (hexane/EtOAc, 3:1) to afford 3a (10.6 mg, 15%) as a
pale yellow liquid, 4a (98.5 mg, 81%) as a pale yellow oil, and 5a (1.7
mg, 2%) as a white solid.
HRMS (FAB): m/z [M + H]+ calcd for C18H18N3: 276.1495; found:
276.1495.
1-Methyl-4-(pent-4-en-1-yn-1-yl)benzene (3c)
Yield: 8.0 mg (13%); yellow liquid; Rf = 0.90 (hexane/EtOAc, 4:1).
1H NMR (400 MHz, CDCl3):  = 7.32 (d, J = 8.0 Hz, 2 H), 7.09 (d, J = 8.0
Hz, 2 H), 5.90 (ddt, J = 16.8, 10.0, 5.2 Hz, 1 H), 5.40 (dq, J = 16.8, 2.0 Hz,
1 H), 5.16 (dq, J = 10.0, 2.0 Hz, 1 H), 3.19 (dt, J = 5.2, 2.0 Hz, 2 H), 2.34
(s, 3 H).
13C NMR (100 MHz, CDCl3):  = 137.9, 132.7, 131.6, 129.1, 120.8,
116.3, 85.9, 83.1, 23.9, 21.5.
1-Methoxy-4-(pent-4-en-1-yn-1-yl)benzene (3a)
Yield: 10.6 mg (15%); pale yellow liquid; Rf = 0.90 (hexane/EtOAc, 2:1).
1H NMR (400 MHz, CDCl3):  = 7.36 (d, J = 8.4 Hz, 2 H), 6.82 (d, J = 8.4
Hz, 2 H), 5.90 (ddt, J = 16.8, 10.4, 5.2 Hz, 1 H), 5.39 (dq, J = 16.8, 2.0 Hz,
1 H), 5.15 (dq, J = 10.4, 2.0 Hz, 1 H), 3.80 (s, 3 H), 3.18 (dt, J = 5.2, 2.0
Hz, 2 H).
HRMS (EI): m/z [M]+ calcd for C12H12: 156.0934; found: 156.0936.
13C NMR (100 MHz, CDCl3):  = 159.4, 133.2, 132.9, 116.3, 116.1,
114.1, 85.2, 82.8, 55.5, 24.0.
HRMS (EI): m/z [M]+ calcd for C12H12O: 172.0883; found: 172.0887.
5-Allyl-1-benzyl-4-(p-tolyl)-1H-1,2,3-triazole (4c)
Yield: 97.2 mg (84%); yellow oil; Rf = 0.15 (hexane/EtOAc, 6:1).
1H NMR (400 MHz, CDCl3):  = 7.57 (d, J = 8.0 Hz, 2 H), 7.37–7.27 (m, 3
H), 7.23 (d, J = 8.0 Hz, 2 H), 7.21–7.17 (m, 2 H), 5.82 (ddt, J = 17.2, 10.4,
5.2 Hz, 1 H), 5.53 (s, 2 H), 5.15 (dq, J = 10.4, 1.2 Hz, 1 H), 4.92 (dq,
J = 17.2, 1.2 Hz, 1 H), 3.43 (dd, J = 5.2, 1.2 Hz, 2 H), 2.38 (s, 3 H).
13C NMR (100 MHz, CDCl3):  = 146.1, 137.8, 135.2, 132.5, 130.1,
129.5, 129.1, 128.6, 128.4, 127.3, 127.2, 117.8, 52.1, 27.2, 21.4.
5-Allyl-1-benzyl-4-(4-methoxyphenyl)-1H-1,2,3-triazole (4a)
Yield: 98.5 mg (81%); pale yellow oil; Rf = 0.26 (hexane/EtOAc, 3:1).
1H NMR (400 MHz, CDCl3):  = 7.61 (d, J = 9.2 Hz, 2 H), 7.38–7.28 (m, 3
H), 7.23–7.16 (m, 2 H), 6.96 (d, J = 9.2 Hz, 2 H), 5.82 (ddt, J = 17.2, 10.4,
5.2 Hz, 1 H), 5.53 (s, 2 H), 5.15 (dtd, J = 10.4, 2.0, 1.2 Hz, 1 H), 4.91
(dtd, J = 17.2, 2.0, 1.2 Hz, 1 H), 3.84 (s, 3 H), 3.42 (dt, J = 5.2, 2.0 Hz, 2
H).
HRMS (ESI): m/z [M + H]+ calcd for C19H20N3: 290.1652; found:
290.1658.
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1-(Pent-4-en-1-yn-1-yl)-4-pentylbenzene (3d)
13C NMR (100 MHz, CDCl3):  = 160.0, 145.9, 135.1, 132.7, 132.3,
130.5, 129.8, 129.1, 128.5, 127.3, 119.6, 117.9, 114.2, 112.5, 55.5, 52.1,
27.2.
HRMS (ESI): m/z [M + H]+ calcd for C19H19N3O: 306.1601; found:
306.1602.
Yield: 3.4 mg (4%); yellow liquid; Rf = 0.88 (hexane/EtOAc, 6:1).
1H NMR (400 MHz, CDCl3):  = 7.33 (d, J = 8.4 Hz, 2 H), 7.10 (d, J = 8.4
Hz, 2 H), 5.90 (ddt, J = 16.8, 10.4, 5.2 Hz, 1 H), 5.40 (dq, J = 16.8, 2.0 Hz,
1 H), 5.16 (dq, J = 10.4, 2.0 Hz, 1 H), 3.19 (dt, J = 5.2, 2.0 Hz, 2 H), 2.58
(t, J = 7.6 Hz, 2 H), 1.65–1.55 (m, 2 H), 1.39–1.24 (m, 4 H), 0.88 (t,
J = 6.8 Hz, 3 H).
1-Benzyl-4-(3-methoxyphenyl)-1H-1,2,3-triazole (5e)
13C NMR (100 MHz, CDCl3):  = 143.0, 132.8, 131.6, 128.5, 121.0,
Yield: 4.8 mg (5%); white solid; mp 79.3–81.3 °C; Rf = 0.15 (hex-
ane/EtOAc, 4:1).
116.3, 85.9, 83.1, 36.0, 31.6, 31.1, 23.9, 22.7, 14.2.
1H NMR (400 MHz, CDCl3):  = 7.65 (s, 1 H), 7.46–7.35 (m, 4 H), 7.34–
7.27 (m, 4 H), 6.87 (dt, J = 6.8, 2.8 Hz, 1 H), 5.58 (s, 2 H), 3.86 (s, 3 H).
HRMS (EI): m/z [M]+ calcd for C16H20: 212.1560; found: 212.1561.
5-Allyl-1-benzyl-4-(4-pentylphenyl)-1H-1,2,3-triazole (4d)
Yield: 106.4 mg (77%); yellow oil; Rf = 0.20 (hexane/EtOAc, 6:1).
13C NMR (100 MHz, CDCl3):  = 160.2, 148.3, 134.8, 132.0, 130.0,
129.3, 128.9, 128.2, 119.8, 118.2, 114.5, 110.8, 55.5, 54.4.
HRMS (ESI): m/z [M + H]+ calcd for C16H15N3O: 266.1288; found:
266.1290.
1H NMR (400 MHz, CDCl3):  = 7.59 (d, J = 8.4 Hz, 2 H), 7.38–7.27 (m, 3
H), 7.23 (d, J = 8.4 Hz, 2 H), 7.21–7.14 (m, 2 H), 5.83 (ddt, J = 17.2, 10.4,
5.2 Hz, 1 H), 5.54 (s, 2 H), 5.15 (dtd, J = 10.4, 2.0, 1.2 Hz, 1 H), 4.92
(dtd, J = 17.2, 2.0, 1.2 Hz, 1 H), 3.44 (dt, J = 5.2, 2.0 Hz, 2 H), 2.62 (t,
J = 8.0 Hz, 2 H), 1.67–1.58 (m, 2 H), 1.39–1.25 (m, 4 H), 0.88 (t, J = 7.2
Hz, 3 H).
13C NMR (100 MHz, CDCl3):  = 146.0, 142.9, 135.1, 132.4, 130.2,
129.1, 128.9, 128.6, 128.4, 127.3, 127.2, 117.8, 52.1, 35.8, 31.6, 31.2,
27.1, 22.7, 14.2.
1,3-Dimethoxy-5-(pent-4-en-1-yn-1-yl)benzene (3f)
Yield: 10 mg (11%); yellow liquid; Rf = 0.70 (hexane/EtOAc, 2:1).
1H NMR (400 MHz, CDCl3):  = 6.52 (d, J = 2.4 Hz, 2 H), 6.35 (t, J = 2.4
Hz, 1 H), 5.83 (ddt, J = 16.8, 10.4, 5.2 Hz, 1 H), 5.33 (dq, J = 16.8, 1.6 Hz,
1 H), 5.10 (dq, J = 10.4, 1.6 Hz, 1 H), 3.70 (s, 6 H), 3.12 (dt, J = 5.2, 1.6
Hz, 2 H).
13C NMR (100 MHz, CDCl3):  = 160.7, 132.6, 125.1, 116.6, 109.7,
101.6, 86.4, 83.0, 55.6, 23.9.
HRMS (ESI): m/z [M + H]+ calcd for C23H28N3: 346.2278; found:
346.2280.
HRMS (ESI): m/z [M + H]+ calcd for C13H15O2: 203.1067; found:
203.1066.
1-Benzyl-4-(4-pentylphenyl)-1H-1,2,3-triazole (5d)
Yield: 7.1 mg (5%); white solid; mp 102.0–104.0 °C; Rf = 0.15 (hex-
ane/EtOAc, 6:1).
5-Allyl-1-benzyl-4-(3,5-dimethoxyphenyl)-1H-1,2,3-triazole (4f)
1H NMR (400 MHz, CDCl3):  = 7.70 (d, J = 8.4 Hz, 2 H), 7.62 (s, 1 H),
7.43–7.33 (m, 3 H), 7.33–7.28 (m, 2 H), 7.21 (d, J = 8.4 Hz, 2 H), 5.57 (s,
2 H), 2.62 (t, J = 7.6 Hz, 2 H), 1.61 (quin, J = 7.6 Hz, 2 H), 1.36–1.28 (m,
4 H), 0.88 (t, J = 7.2 Hz, 3 H).
13C NMR (100 MHz, CDCl3):  = 148.5, 143.3, 135.0, 129.3, 129.0,
128.9, 128.2, 128.1, 125.8, 119.3, 54.4, 35.8, 31.6, 31.2, 22.7, 14.2.
Yield: 108 mg (81%); white solid; mp 76.5–78.5 °C; Rf = 0.23 (hex-
ane/EtOAc, 2:1).
1H NMR (400 MHz, CDCl3):  = 7.30–7.20 (m, 3 H), 7.14–7.09 (m, 2 H),
6.79 (d, J = 2.4 Hz, 2 H), 6.39 (t, J = 2.4 Hz, 1 H), 5.75 (ddt, J = 17.2, 10.4,
5.2 Hz, 1 H), 5.46 (s, 2 H), 5.09 (dtd, J = 10.4, 2.0, 1.2 Hz, 1 H), 4.84
(dtd, J = 17.2, 2.0, 1.2 Hz, 1 H), 3.75 (s, 6 H), 3.39 (dt, J = 5.2, 2.0 Hz, 2
H).
HRMS (ESI): m/z [M + H]+ calcd for C20H24N3: 306.1965; found:
13C NMR (100 MHz, CDCl3):  = 160.9, 145.6, 134.8, 133.0, 132.1,
306.1956.
130.4, 128.9, 128.2, 127.1, 117.7, 105.0, 100.2, 55.4, 51.9, 27.0.
1-Methoxy-3-(pent-4-en-1-yn-1-yl)benzene (3e)
HRMS (ESI): m/z [M + H]+ calcd for C20H22N3O2: 336.1707; found:
Yield: 10.6 mg (15%); yellow liquid; Rf = 0.75 (hexane/EtOAc, 4:1).
336.1707.
1H NMR (400 MHz, CDCl3):  = 7.20 (t, J = 8.0 Hz, 1 H), 7.03 (dt, J = 8.0,
1.2 Hz, 1 H), 6.99–6.94 (m, 1 H), 6.85 (ddd, J = 8.0, 2.8, 0.8 Hz, 1 H),
5.91 (ddt, J = 17.2, 10.0, 2.0 Hz, 1 H), 5.40 (dq, J = 17.2, 2.0 Hz, 1 H),
5.17 (dq, J = 10.0, 2.0 Hz, 1 H), 3.80 (s, 3 H), 3.20 (dt, J = 5.2, 2.0 Hz, 2
H).
13C NMR (100 MHz, CDCl3):  = 159.4, 132.5, 129.4, 124.8, 124.3,
116.6, 116.4, 114.5, 86.6, 82.9, 55.4, 23.8.
1-Benzyl-4-(3,5-dimethoxyphenyl)-1H-1,2,3-triazole (5f)
Yield: 7.5 mg (6%); white solid; mp 118.4–120.4 °C; Rf = 0.16 (hex-
ane/EtOAc, 2:1).
1H NMR (400 MHz, CDCl3):  = 7.56 (s, 1 H), 7.36–7.29 (m, 3 H), 7.27–
7.22 (m, 2 H), 6.90 (d, J = 2.4 Hz, 2 H), 6.36 (t, J = 2.4 Hz, 1 H), 5.51 (s, 2
H), 3.76 (s, 6 H).
HRMS (EI): m/z [M]+ calcd for C12H12O: 172.0883; found: 172.0887.
13C NMR (100 MHz, CDCl3):  = 161.1, 148.1, 134.6, 132.3, 129.2,
128.8, 128.0, 119.8, 103.6, 100.6, 55.5, 54.2.
5-Allyl-1-benzyl-4-(3-methoxyphenyl)-1H-1,2,3-triazole (4e)
Yield: 91.4 mg (75%); yellow oil; Rf = 0.20 (hexane/EtOAc, 4:1).
HRMS (ESI): m/z [M + H]+ calcd for C17H18N3O2: 296.1394; found:
296.1393.
1H NMR (400 MHz, CDCl3):  = 7.39–7.27 (m, 5 H), 7.23 (dt, J = 8.4, 1.2
Hz, 1 H), 7.21–7.17 (m, 2 H), 6.90 (ddd, J = 8.4, 1.6, 1.2 Hz, 1 H), 5.83
(ddt, J = 17.2, 10.0, 5.2 Hz, 1 H), 5.54 (s, 2 H), 5.15 (dtd, J = 10.0, 2.0, 1.2
Hz, 1 H), 4.92 (dtd, J = 17.2, 2.0, 1.2 Hz, 1 H), 3.84 (s, 3 H), 3.46 (dt,
J = 5.2, 2.0 Hz, 2 H).
1-Fluoro-4-(pent-4-en-1-yn-1-yl)benzene (3g)
Yield: 5.4 mg (8%); yellow liquid; Rf = 0.98 (hexane/EtOAc, 4:1).
© 2019. Thieme. All rights reserved. Synthesis 2019, 51, A–K

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1H NMR (400 MHz, CDCl3):  = 7.38 (dd, J = 8.8, 5.6 Hz, 2 H), 6.98 (t,
J = 8.8 Hz, 2 H), 5.89 (ddt, J = 16.8, 10.0, 5.2 Hz, 1 H), 5.39 (dq, J = 16.8,
1.6 Hz, 1 H), 5.16 (dq, J = 10.0, 1.6 Hz, 1 H), 3.18 (dt, J = 5.2, 1.6 Hz, 2
H).
13C NMR (100 MHz, CDCl3):  = 162.3 (d, JC–F = 248.6 Hz), 133.5 (d,
JC–F = 8.5 Hz), 132.5, 119.9 (d, JC–F = 3.5 Hz), 116.4, 115.6 (d, JC–F = 21.8
Hz), 86.4, 81.9, 23.8.
5-Allyl-1-benzyl-4-(3,5-difluorophenyl)-1H-1,2,3-triazole (4i)
Yield: 89.3 mg (72%); yellow oil; Rf = 0.15 (hexane/EtOAc, 6:1).
1H NMR (400 MHz, CDCl3):  = 7.40–7.28 (m, 3 H), 7.28–7.15 (m, 4 H),
6.83–6.72 (m, 1 H), 5.80 (ddt, J = 17.2, 10.4, 5.2 Hz, 1 H), 5.54 (s, 2 H),
5.18 (dtd, J = 10.4, 2.0, 1.2 Hz, 1 H), 4.88 (dtd, J = 17.2, 2.0, 1.2 Hz, 1 H),
3.46 (dt, J = 5.2, 2.0 Hz, 2 H).
13C NMR (100 MHz, CDCl3):  = 163.4 (dd, JC–F = 246.5, 13.1 Hz), 143.9,
134.7, 134.5 (t, JC–F = 11.0 Hz), 131.6, 131.1, 129.2, 128.6, 127.4, 118.3,
109.9 (dd, JC–F = 19.0, 7.4 Hz), 103.2 (t, JC–F = 25.0 Hz), 52.3, 27.0.
HRMS (EI): m/z [M]+ calcd for C11H9F: 160.0688; found: 160.0690.
5-Allyl-1-benzyl-4-(4-fluorophenyl)-1H-1,2,3-triazole (4g)
Yield: 103.5 mg (88%); yellow oil; Rf = 0.28 (hexane/EtOAc, 6:1).
HRMS (ESI): m/z [M + H]+ calcd for C18H16F2N3: 312.1307; found:
312.1306.
1H NMR (400 MHz, CDCl3):  = 7.65 (dd, J = 8.8, 5.2 Hz, 2 H), 7.37–7.30
(m, 3 H), 7.23–7.17 (m, 2 H), 7.12 (t, J = 8.8 Hz, 2 H), 5.81 (ddt, J = 17.2,
10.4, 5.2 Hz, 1 H), 5.54 (s, 2 H), 5.16 (dtd, J = 10.4, 2.0, 0.8 Hz, 1 H),
4.90 (dtd, J = 17.2, 2.0, 0.8 Hz, 1 H), 3.42 (dt, J = 5.2, 2.0 Hz, 2 H).
1-Benzyl-4-(3,5-difluorophenyl)-1H-1,2,3-triazole (5i)
Yield: 10.8 mg (10%); white solid; mp 123.0–125.0 °C; Rf = 0.15 (hex-
ane/EtOAc, 6:1).
13C NMR (100 MHz, CDCl3):  = 162.7 (d, JC–F = 247.2 Hz), 145.2, 135.0,
132.2, 130.2, 129.2, 129.1 (d, JC–F = 8.2 Hz), 128.5, 127.6 (d, JC–F = 3.5
Hz), 127.4, 118.0, 115.8 (d, JC–F = 21.5 Hz), 52.2, 27.1.
HRMS (ESI): m/z [M + H]+ calcd for C18H17FN3: 294.1401; found:
294.1405.
1H NMR (400 MHz, CDCl3):  = 7.66 (s, 1 H), 7.40 (dd, J = 5.9, 1.6 Hz, 3
H), 7.36–7.27 (m, 4 H), 6.75 (tt, J = 8.8, 1.6 Hz, 1 H), 5.58 (s, 2 H).
13C NMR (100 MHz, CDCl3):  = 163.5 (dd, JC–F = 246.6, 3.0 Hz), 134.4,
133.9, 133.8, 129.4, 129.2, 128.3, 120.3, 108.7 (dd, JC–F = 19.2, 0.8 Hz),
103.5 (t, JC–F = 25.4 Hz), 54.6.
HRMS (ESI): m/z [M + H]+ calcd for C15H12F2N3: 272.0994; found:
272.0991.
5-Allyl-1-benzyl-4-(3-fluorophenyl)-1H-1,2,3-triazole (4h)
Yield: 74.2 mg (63%); yellow oil; Rf = 0.16 (hexane/EtOAc, 6:1).
1H NMR (400 MHz, CDCl3):  = 7.47 (dt, J = 8.0, 1.2 Hz, 1 H), 7.44–7.28
(m, 5 H), 7.25–7.16 (m, 2 H), 7.04 (tdd, J = 8.0, 2.8, 1.2 Hz, 1 H), 5.81
(ddt, J = 17.2, 10.4, 5.2 Hz, 1 H), 5.54 (s, 2 H), 5.17 (dtd, J = 10.4, 2.0, 1.2
Hz, 1 H), 4.91 (dtd, J = 17.2, 2.0, 1.2 Hz, 1 H), 3.46 (dt, J = 5.2, 2.0 Hz, 2
H).
13C NMR (100 MHz, CDCl3):  = 163.1 (d, JC–F = 245.6 Hz), 144.9 (d,
JC–F = 2.7 Hz), 134.9, 133.5 (d, JC–F = 8.3 Hz), 132.0, 130.8, 130.4 (d,
JC–F = 8.5 Hz), 129.2, 128.5, 127.3, 122.8 (d, JC–F = 2.9 Hz), 118.1, 114.8
(d, JC–F = 21.1 Hz), 114.2 (d, JC–F = 22.8 Hz), 52.2, 27.1.
5-Allyl-1-benzyl-4-[4-(trifluoromethyl)phenyl]-1H-1,2,3-triazole
(4j)
Yield: 125.8 mg (92%); yellow oil; Rf = 0.20 (hexane/EtOAc, 6:1).
1H NMR (400 MHz, CDCl3):  = 7.82 (dm, J = 7.2 Hz, 2 H), 7.68 (dm,
J = 7.2 Hz, 2 H), 7.40–7.28 (m, 3 H), 7.24–7.17 (m, 2 H), 5.82 (ddt,
J = 17.2, 10.0, 5.2 Hz, 1 H), 5.56 (s, 2 H), 5.18 (dtd, J = 10.0, 2.0, 1.2 Hz,
1 H), 4.91 (dtd, J = 17.2, 2.0, 1.2 Hz, 1 H), 3.47 (dt, J = 5.2, 2.0 Hz, 2 H).
13C NMR (100 MHz, CDCl3):  = 144.7, 135.0 (q, JC–F = 1.3 Hz), 134.8,
131.8, 131.2, 129.9 (q, JC–F = 32.4 Hz), 129.2, 128.6, 127.4, 127.4, 125.8
(q, JC–F = 3.9 Hz), 124.3 (q, JC–F = 272.1 Hz), 118.2, 52.3, 27.1.
HRMS (ESI): m/z [M + H]+ calcd for C18H17FN3: 294.1401; found:
294.1398.
HRMS (ESI): m/z [M + H]+ calcd for C19H17F3N3: 344.1369; found:
344.1372.
1-Benzyl-4-(3-fluorophenyl)-1H-1,2,3-triazole (5h)
Yield: 10.3 mg (10%); white solid; mp 109.1–111.1 °C; Rf = 0.10 (hex-
ane/EtOAc, 6:1).
1-Benzyl-4-[4-(trifluoromethyl)phenyl]-1H-1,2,3-triazole (5j)
Yield: 5.0 mg (4%); white solid; mp 134.4–136.4 °C; Rf = 0.13 (hex-
ane/EtOAc, 6:1).
1H NMR (400 MHz, CDCl3):  = 7.66 (s, 1 H), 7.56 (dt, J = 7.6, 1.2 Hz, 1
H), 7.52 (ddd, J = 9.6, 2.8, 1.6 Hz, 1 H), 7.49–7.28 (m, 6 H), 7.01 (tdd,
J = 8.4, 2.8, 1.2 Hz, 1 H), 5.59 (s, 2 H).
13C NMR (100 MHz, CDCl3):  = 163.3 (d, JC–F = 245.7 Hz), 134.6, 132.8
(d, JC–F = 8.5 Hz), 130.5 (d, JC–F = 8.5 Hz), 129.4, 129.1, 128.3, 121.5,
121.4, 120.0, 115.1 (d, JC–F = 21.1 Hz), 112.8 (d, JC–F = 23.1 Hz), 54.5.
1H NMR (400 MHz, CDCl3):  = 7.92 (dm, J = 8.0 Hz, 2 H), 7.73 (s, 1 H),
7.66 (dm, J = 8.0 Hz, 2 H), 7.44–7.37 (m, 3 H), 7.35–7.30 (m, 2 H), 5.60
(s, 2 H).
13C NMR (100 MHz, CDCl3):  = 147.0, 134.5, 134.1, 130.2 (q, JC–F
32.5 Hz), 129.4, 129.1, 128.3, 125.9 (q, JC–F = 3.6 Hz), 122.9 (q, JC–F
31.8 Hz), 120.4, 54.5.
=
=
HRMS (ESI): m/z [M + H]+ calcd for C15H12FN3: 254.1088; found:
254.1089.
HRMS (ESI): m/z [M + H]+ calcd for C16H13F3N3: 304.1056; found:
304.1057.
1,3-Difluoro-5-(pent-4-en-1-yn-1-yl)benzene (3i)
Yield: 5.0 mg (7%); yellow liquid; Rf = 0.85 (hexane/EtOAc, 6:1).
1-Nitro-4-(pent-4-en-1-yn-1-yl)benzene (3k)
1H NMR (400 MHz, CDCl3):  = 6.98–6.88 (m, 2 H), 6.74 (tt, J = 8.8, 2.0
Hz, 1 H), 5.88 (ddt, J = 17.2, 10.0, 5.2 Hz, 1 H), 5.37 (dq, J = 17.2, 2.0 Hz,
1 H), 5.18 (dq, J = 10.0, 2.0 Hz, 1 H), 3.19 (dt, J = 5.2, 2.0 Hz, 2 H).
13C NMR (100 MHz, CDCl3):  = 162.8 (dd, JC–F = 248.3, 13.3 Hz), 131.9,
126.6 (t, JC–F = 11.7 Hz), 116.8, 114.7 (dd, JC–F = 19.0, 7.4 Hz), 104.1 (t,
JC–F = 25.3 Hz), 89.2, 81.0 (t, JC–F = 3.9 Hz), 23.7.
Yield: 4.6 mg (6%); yellow oil; Rf = 0.77 (hexane/EtOAc, 2:1).
1H NMR (400 MHz, CDCl3):  = 8.10 (d, J = 8.8 Hz, 2 H), 7.48 (d, J = 8.8
Hz, 2 H), 5.82 (ddt, J = 17.2, 10.0, 5.2 Hz, 1 H), 5.32 (dq, J = 17.0, 1.6 Hz,
1 H), 5.13 (dq, J = 10.0, 1.6 Hz, 1 H), 3.18 (dt, J = 5.2, 1.6 Hz, 2 H).
13C NMR (100 MHz, CDCl3):  = 146.9, 132.5, 131.7, 130.9, 123.7,
117.0, 92.9, 81.5, 24.0.
HRMS (EI): m/z [M]+ calcd for C11H8F2 [M]+: 178.0589; found:
178.0594.
HRMS (EI): m/z [M]+ calcd for C11H9NO2: 187.0628; found: 187.0634.
© 2019. Thieme. All rights reserved. Synthesis 2019, 51, A–K

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5-Allyl-1-benzyl-4-(4-nitrophenyl)-1H-1,2,3-triazole (4k)
5-Allyl-1-benzyl-4-[3,5-bis(trifluoromethyl)phenyl]-1H-1,2,3-tri-
azole (4m)
Yield: 67.9 mg (53%); yellow solid; mp 88.2–100.2 °C; Rf = 0.23 (hex-
ane/EtOAc, 2:1).
Yield: 97.4 mg (59%); white solid; mp 95.1–97.1 °C; Rf = 0.20 (hex-
ane/EtOAc, 7:1).
1H NMR (400 MHz, CDCl3):  = 8.21 (d, J = 8.8 Hz, 2 H), 7.82 (d, J = 8.8
Hz, 2 H), 7.34–7.22 (m, 3 H), 7.14 (d, J = 8.4 Hz, 2 H), 5.76 (ddt,
J = 17.2, 10.4, 5.2 Hz, 1 H), 5.49 (s, 2 H), 5.12 (dtd, J = 10.4, 2.0, 0.8 Hz,
1 H), 4.83 (ddd, J = 17.2, 2.0, 0.8 Hz, 1 H), 3.44 (dt, J = 5.2, 2.0 Hz. 2 H).
13C NMR (100 MHz, CDCl3):  = 147.1, 143.7, 137.7, 134.4, 131.8,
131.3, 129.1, 128.5, 127.4, 127.2, 124.0, 118.3, 52.2, 27.0.
1H NMR (400 MHz, CDCl3):  = 8.18 (s, 2 H), 7.84 (s, 1 H), 7.41–7.29
(m, 3 H), 7.23–7.17 (m, 2 H), 5.75 (ddt, J = 17.2, 10.4, 5.2 Hz, 1 H), 5.58
(s, 2 H), 5.20 (dtd, J = 10.4, 2.0, 0.8 Hz, 1 H), 4.95 (dtd, J = 17.2, 2.0, 0.8
Hz, 1 H), 3.49 (dt, J = 5.2, 2.0 Hz, 2 H).
13C NMR (100 MHz, CDCl3):  = 143.4, 134.6, 133.5, 132.2 (q, JC–F
33.0 Hz), 131.7, 131.3, 129.3, 128.8, 127.4, 127.1 (m), 123.4 (q, JC–F
271.3 Hz), 121.5 (q, JC–F = 3.6 Hz), 118.7, 52.4, 27.3.
=
=
HRMS (ESI): m/z [M + Na]+ calcd for C18H16N4O2Na: 343.1165; found:
343.1166.
HRMS (ESI): m/z [M + H]+ calcd for C20H16F6N3: 412.1243; found:
412.1247.
1-Benzyl-4-(4-nitrophenyl)-1H-1,2,3-triazole (5k)
Yield: 35.0 mg (31%); yellow solid; mp 170.9–172.9 °C; Rf = 0.23 (hex-
ane/EtOAc, 2:1).
1H NMR (400 MHz, CDCl3):  = 8.23–8.16 (m, 2 H), 7.93–7.87 (m, 2 H),
7.72 (s, 1 H), 7.39–7.31 (m, 3 H), 7.31–7.24 (m, 2 H), 5.53 (s, 2 H).
13C NMR (100 MHz, CDCl3):  = 147.3, 146.0, 136.8, 134.1, 129.3,
129.0, 128.2, 126.1, 124.2, 120.9, 54.5.
HRMS (ESI): m/z [M + H]+ calcd for C15H13N4O2: 281.1033; found:
281.1032.
1-Benzyl-4-[3,5-bis(trifluoromethyl)phenyl]-1H-1,2,3-triazole
(5m)
Yield: 35.7 mg (24%); white solid; mp 105.0–107.0 °C; Rf = 0.13 (hex-
ane/EtOAc, 7:1).
1H NMR (400 MHz, CDCl3):  = 8.25 (s, 2 H), 7.81 (s, 1 H), 7.81 (s, 1 H),
7.45–7.39 (m, 3 H), 7.39–7.31 (m, 2 H), 5.62 (s, 2 H).
13C NMR (100 MHz, CDCl3):  = 145.7 (m), 134.3, 132.8, 132.4 (q, JC–F
33.3 Hz), 129.5, 129.3, 128.4, 125.7 (m), 123.4 (q, JC–F = 271.3 Hz),
121.7 (q, JC–F = 4.0 Hz), 120.6, 54.7.
HRMS (ESI): m/z [M + H]+ calcd for C17H12F6N3: 372.0930; found:
372.0935.
=
4-(Pent-4-en-1-yn-1-yl)benzonitrile (3l)
Yield: 5.0 mg (7%); pale yellow liquid; Rf = 0.88 (hexane/EtOAc, 3:1).
1H NMR (400 MHz, CDCl3):  = 7.51 (d, J = 8.8 Hz, 2 H), 7.42 (d, J = 8.8
Hz, 2 H), 5.81 (ddt, J = 16.8, 10.4, 5.2 Hz, 1 H), 5.31 (dq, J = 16.8, 1.6 Hz,
1 H), 5.12 (dq, J = 10.4, 1.6 Hz, 1 H), 3.15 (dt, J = 5.2, 1.6 Hz, 2 H).
13C NMR (100 MHz, CDCl3):  = 132.1, 131.9, 131.6, 128.7, 118.5,
116.7, 111.1, 91.7, 81.5, 23.7.
5-Allyl-1-benzyl-4-cyclohexyl-1H-1,2,3-triazole (4n)
Yield: 72.1 mg (64%); yellow liquid; Rf = 0.20 (hexane/EtOAc, 5:1).
1H NMR (400 MHz, CDCl3):  = 7.36–7.26 (m, 3 H), 7.16–7.08 (m, 2 H),
5.66 (ddt, J = 17.2, 10.4, 5.2 Hz, 1 H), 5.45 (s, 2 H), 5.06 (dq, J = 10.4, 1.6
Hz, 1 H), 4.87 (dq, J = 17.2, 1.6 Hz, 1 H), 3.23 (dq, J = 5.2, 1.6 Hz, 2 H),
2.56 (tt, J = 12.0, 3.6 Hz, 1 H), 1.89–1.77 (m, 4 H), 1.77–1.67 (m, 3 H),
1.62–1.59 (m, 1 H), 1.34–1.29 (m, 2 H).
HRMS (EI): m/z [M]+ calcd for C12H9N: 167.0730; found: 167.0736.
4-(5-Allyl-1-benzyl-1H-1,2,3-triazol-4-yl)benzonitrile (4l)
Yield: 83 mg (69%); yellow solid; mp 78.9–80.9 °C; Rf = 0.26 (hex-
ane/EtOAc, 2:1).
13C NMR (100 MHz, CDCl3):  = 150.8, 135.5, 133.0, 129.2, 129.0,
128.2, 127.2, 117.2, 51.9, 35.3, 32.9, 26.8, 26.7, 26.0.
1H NMR (400 MHz, CDCl3):  = 7.75 (d, J = 8.8 Hz, 2 H), 7.62 (d, J = 8.8
Hz, 2 H), 7.31–7.21 (m, 3 H), 7.16–7.10 (m, 2 H), 5.74 (ddt, J = 17.2,
10.0, 5.2 Hz, 1 H), 5.47 (s, 2 H), 5.10 (dtd, J = 10.0, 2.0, 0.8 Hz, 1 H),
4.81 (dtd, J = 17.2, 2.0, 0.8 Hz, 1 H), 3.41 (dt, J = 5.2, 2.0 Hz, 2 H).
13C NMR (100 MHz, CDCl3):  = 144.1, 136.0, 134.7, 132.7, 131.6,
131.5, 129.2, 128.7, 127.5, 127.4, 119.0, 118.4, 111.4, 52.3, 27.2.
HRMS (ESI): m/z [M + Na]+ calcd for C18H23N3Na: 304.1784; found:
305.1783.
Undec-1-en-4-yne (3o)
Yield: 5 mg (8%); pale yellow liquid; Rf = 0.88 (hexane/EtOAc, 2:1).
1H NMR (400 MHz, CDCl3):  = 5.82 (ddt, J = 16.8, 10.0, 5.2 Hz, 1 H),
5.32 (dq, J = 16.8, 2.0 Hz, 1 H), 5.08 (dq, J = 10.0, 2.0 Hz, 1 H), 2.95–
2.92 (m, 2 H), 2.17 (tt, J = 7.2, 2.4 Hz, 2 H), 1.54–1.47 (m, 2 H), 1.43–
1.35 (m, 2 H), 1.34–1.23 (m, 4 H), 0.88 (t, J = 7.2 Hz, 3 H).
13C NMR (100 MHz, CDCl3):  = 133.9, 115.9, 83.3, 76.9, 31.8, 29.5,
29.0, 23.6, 23.0, 19.2, 14.5.
HRMS (ESI): m/z [M + H]+ calcd for C19H17N4: 301.1448; found:
301.1452.
4-(1-Benzyl-1H-1,2,3-triazol-4-yl)benzonitrile (5l)
Yield: 25.4 mg (24%); bright yellow solid; mp 139.7–141.7 °C; Rf =
0.29 (hexane/EtOAc, 2:1).
1H NMR (400 MHz, CDCl3):  = 7.83 (d, J = 8.8 Hz, 2 H), 7.70 (s, 1 H),
7.59 (d, J = 8.8 Hz, 2 H), 7.37–7.29 (m, 3 H), 7.28–7.20 (m, 2 H), 5.52 (s,
2 H).
13C NMR (100 MHz, CDCl3):  = 146.3, 134.9, 134.2, 132.6, 129.2,
129.0, 128.1, 126.0, 120.6, 118.7, 111.4, 54.4.
HRMS (ESI): m/z [M + Cl]– calcd for C16H12N4Cl: 295.0756; found:
295.0752.
HRMS (ESI): m/z [M]+ calcd for C11H18: 150.1409; found: 150.1408.
5-Allyl-1-benzyl-4-hexyl-1H-1,2,3-triazole (4o)
Yield: 81 mg (71%); pale yellow liquid; Rf = 0.35 (hexane/EtOAc, 2:1).
1H NMR (400 MHz, CDCl3):  = 7.36–7.27 (m, 3 H), 7.15–7.10 (m, 2 H),
5.65 (ddt, J = 17.2, 10.0, 6.0 Hz, 1 H), 5.47 (s, 2 H), 5.07 (dq, J = 10.0, 1.6
Hz, 1 H), 4.89 (dq, J = 17.2, 1.6 Hz, 1 H), 3.22 (dt, J = 6.0, 1.6 Hz, 2 H),
2.61 (t, J = 8.0 Hz, 2 H), 1.66 (t, J = 8.0 Hz, 2 H), 1.41–1.19 (m, 6 H),
0.86 (t, J = 6.8 Hz, 3 H).
13C NMR (100 MHz, CDCl3):  = 146.2, 135.2, 132.4, 130.0, 128.8,
128.1, 127.0, 117.1, 51.8, 31.5, 29.5, 29.0, 26.5, 25.0, 22.5, 14.0.
© 2019. Thieme. All rights reserved. Synthesis 2019, 51, A–K

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Y. Song et al.
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Synthesis
HRMS (ESI): m/z [M + H]+ calcd for C18H26N3: 284.2121; found:
HRMS (ESI): m/z [M + H]+ calcd for C14H11BrN3: 300.0131; found:
284.2127.
300.0141.
4-[(5-Allyl-4-phenyl-1H-1,2,3-triazol-1-yl)methyl]benzonitrile
1-Methoxy-4-(pent-4-en-1-yn-1-yl)benzene (3r)
(4p)
Yield: 10.7 mg (16%); bright yellow liquid; Rf = 0.90 (hexane/EtOAc,
Yield: 63.6 mg (53%); yellow liquid; Rf = 0.26 (hexane/EtOAc, 2:1).
2:1).
1H NMR (400 MHz, CDCl3):  = 7.68 (d, J = 8.0 Hz, 2 H), 7.65 (d, J = 8.0
Hz, 2 H), 7.44 (t, J = 8.0 Hz, 2 H), 7.37 (t, J = 8.0 Hz, 1 H), 7.29 (t, J = 8.0
Hz, 2 H), 5.84 (ddt, J = 17.2, 10.4, 5.2 Hz, 1 H), 5.59 (s, 2 H), 5.17 (dtd,
J = 10.4, 2.0, 1.2 Hz, 1 H), 4.90 (dtd, J = 17.2, 2.0, 1.2 Hz, 1 H), 3.46 (dt,
J = 5.2, 2.0 Hz, 2 H).
1H NMR (400 MHz, CDCl3):  = 7.36 (d, J = 8.4 Hz, 2 H), 6.82 (d, J = 8.4
Hz, 2 H), 5.90 (ddt, J = 16.8, 10.4, 5.2 Hz, 1 H), 5.39 (dq, J = 16.8, 2.0 Hz,
1 H), 5.15 (dq, J = 10.4, 2.0 Hz, 1 H), 3.80 (s, 3 H), 3.18 (dt, J = 5.2, 2.0
Hz, 2 H).
13C NMR (100 MHz, CDCl3):  = 159.4, 133.1, 132.9, 116.3, 116.1,
114.1, 85.1, 82.8, 55.5, 24.0.
13C NMR (100 MHz, CDCl3):  = 146.2, 140.4, 133.0, 132.1, 131.1,
130.5, 129.0, 128.3, 128.0, 127.3, 118.4, 118.2, 112.6, 51.4, 27.2.
HRMS (ESI): m/z [M + H]+ calcd for C19H17N4: 301.1448; found:
HRMS (EI): m/z [M]+ calcd for C12H12O: 172.0883; found: 172.0887.
301.1452.
4-{[5-Allyl-4-(4-methoxyphenyl)-1H-1,2,3-triazol-1-yl]methyl}-
benzonitrile (4r)
4-[(4-Phenyl-1H-1,2,3-triazol-1-yl)methyl]benzonitrile (5p)
Yield: 76.6 mg (58%); bright yellow oil; Rf = 0.26 (hexane/EtOAc, 2:1).
Yield: 5.8 mg (6%); white solid; mp 127.5–129.5 °C; Rf = 0.18 (hex-
ane/EtOAc, 2:1).
1H NMR (400 MHz, CDCl3):  = 7.81 (d, J = 7.6 Hz, 2 H), 7.72 (s, 1 H),
7.69 (d, J = 8.4 Hz, 2 H), 7.45–7.32 (m, 5 H), 5.66 (s, 2 H).
13C NMR (100 MHz, CDCl3):  = 148.9, 140.1, 133.2, 130.3, 129.1,
1H NMR (400 MHz, CDCl3):  = 7.64 (d, J = 8.4 Hz, 2 H), 7.60 (d, J = 8.4
Hz, 2 H), 7.29 (d, J = 8.4 Hz, 2 H), 6.98 (d, J = 8.4 Hz, 2 H), 5.82 (ddt,
J = 17.2, 10.4, 5.2 Hz, 1 H), 5.57 (s, 2 H), 5.15 (dtd, J = 10.4, 2.0, 1.2 Hz,
1 H), 4.88 (dtd, J = 17.2, 2.0, 1.2 Hz, 1 H), 3.84 (s, 3 H), 3.43 (dt, J = 5.2,
2.0 Hz, 2 H).
128.7, 128.6, 126.0, 119.8, 118.3, 113.1, 53.7.
13C NMR (100 MHz, CDCl3):  = 159.7, 146.0, 140.4, 132.9, 132.2,
129.8, 128.6, 128.0, 123.6, 118.4, 118.1, 114.3, 112.5, 55.4, 51.3, 27.1.
HRMS (ESI): m/z [M + H]+ calcd for C20H19N4O: 331.1553; found:
HRMS (ESI): m/z [M + H]+ calcd for C16H13N4: 261.1135; found:
261.1135.
331.1550.
Pent-4-en-1-yn-1-ylbenzene (3q)
4-{[4-(4-Methoxyphenyl)-1H-1,2,3-triazol-1-yl]methyl}benzo-
nitrile (5r)
Yield: 7.5 mg (13%); bright yellow liquid; Rf = 0.88 (hexane/EtOAc,
4:1).
Yield: 11.4 mg (10%); white solid; mp 143.0–145.0 °C T; Rf = 0.21
(hexane/EtOAc, 2:1).
1H NMR (400 MHz, CDCl3):  = 7.74 (d, J = 8.8 Hz, 2 H), 7.68 (d, J = 8.4
Hz, 2 H), 7.63 (s, 1 H), 7.38 (d, J = 8.4 Hz, 2 H), 6.95 (d, J = 8.8 Hz, 2 H),
5.63 (s, 2 H), 3.84 (s, 3 H).
13C NMR (100 MHz, CDCl3):  = 160.0, 148.8, 140.2, 133.1, 128.5,
127.3, 123.0, 119.0, 118.3, 114.5, 113.0, 55.5, 53.6.
1H NMR (400 MHz, CDCl3):  = 7.45–7.37 (m, 2 H), 7.30–7.21 (m, 3 H),
5.87 (ddt, J = 16.8, 10.0, 5.2 Hz, 1 H), 5.40 (dq, J = 16.8, 1.6 Hz, 1 H),
5.15 (dq, J = 10.0, 1.6 Hz, 1 H), 3.16 (dt, J = 5.2, 1.6 Hz, 2 H).
13C NMR (100 MHz, CDCl3):  = 132.5, 131.6, 128.3, 127.8, 123.8,
116.3, 86.6, 83.0, 23.8
HRMS (EI): m/z [M]+ calcd for C11H10: 142.0783; found: 142.0781.
HRMS (ESI): m/z [M + Cl]– calcd for C17H15N4OCl: 325.0862; found:
325.0857.
5-Allyl-1-(2-bromophenyl)-4-phenyl-1H-1,2,3-triazole (4q)
Yield: 50.8 mg (37%); white solid; mp 99.2–101.2 °C; Rf = 0.28 (hex-
ane/EtOAc, 4:1).
1-(Pent-4-en-1-yn-1-yl)-4-(trifluoromethyl)benzene (3s)
1H NMR (400 MHz, CDCl3):  = 7.83 (d, J = 7.2 Hz, 2 H), 7.78 (d, J = 8.0
Hz, 1 H), 7.52–7.43 (m, 5 H), 7.39 (tt, J = 7.2, 1.6 Hz, 1 H), 5.74 (ddt,
J = 17.2, 10.0, 5.6 Hz, 1 H), 5.05 (dtd, J = 10.0, 2.0, 1.2 Hz, 1 H), 4.84
(dtd, J = 17.2, 2.0, 1.2 Hz, 1 H), 3.51 (m, 2 H).
13C NMR (100 MHz, CDCl3):  = 145.0, 135.8, 134.0, 132.5, 132.4,
132.2, 131.3, 130.0, 129.0, 128.5, 128.3, 127.5, 122.3, 118.1, 27.8.
Yield: 8.4 mg (10%); bright yellow liquid; Rf = 0.79 (hexane/EtOAc,
6:1).
1H NMR (400 MHz, CDCl3):  = 7.55 (d, J = 8.4 Hz, 2 H), 7.51 (d, J = 8.4
Hz, 2 H), 5.90 (ddt, J = 16.8, 10.0, 5.2 Hz, 1 H), 5.40 (dq, J = 16.8, 1.6 Hz,
1 H), 5.19 (dq, J = 10.0, 1.6 Hz, 1 H), 3.21 (dt, J = 5.2, 1.6 Hz, 2 H).
13C NMR (100 MHz, CDCl3):  = 131.9, 131.8, 129.5 (q, JC–F = 32.4 Hz),
127.5, 125.1 (q, JC–F = 3.8 Hz), 124.0 (q, JC–F = 270.4 Hz), 116.5, 89.4,
81.6, 23.7.
HRMS (ESI): m/z [M + Na]+ calcd for C17H14BrN3Na: 362.0263; found:
362.0267.
HRMS (EI): m/z [M]+ calcd for C12H9F3: 210.0656; found: 210.0655.
1-(2-Bromophenyl)-4-phenyl-1H-1,2,3-triazole (5q)
Yield: 3.7 mg (3%); white solid; mp 100.1–102.1 °C; Rf = 0.38 (hex-
ane/EtOAc, 4:1).
1H NMR (400 MHz, CDCl3):  = 8.17 (s, 1 H), 7.93 (d, J = 8.0 Hz, 2 H),
7.79 (dd, J = 8.0, 1.6 Hz, 1 H), 7.62 (dd, J = 8.0, 1.6 Hz, 1 H), 7.53 (dd,
J = 7.6, 1.2 Hz, 1 H), 7.50–7.36 (m, 4 H).
13C NMR (100 MHz, CDCl3):  = 147.7, 136.8, 134.1, 131.4, 130.4,
129.1, 128.7, 128.6, 128.4, 126.1, 121.9, 118.8.
4-({5-Allyl-4-[4-(trifluoromethyl)phenyl]-1H-1,2,3-triazol-1-
yl}methyl)benzonitrile (4s)
Yield: 111.6 mg (76%); pale yellow oil; Rf = 0.26 (hexane/EtOAc, 3:1).
1H NMR (400 MHz, CDCl3):  = 7.83 (d, J = 8.4 Hz, 2 H), 7.71 (d, J = 8.4
Hz, 2 H), 7.68 (d, J = 8.4 Hz, 2 H), 7.32 (d, J = 8.4 Hz, 2 H), 5.85 (ddt,
J = 17.2, 10.0, 5.2 Hz, 1 H), 5.61 (s, 2 H), 5.20 (dq, J = 10.0, 1.6 Hz, 1 H),
4.90 (dq, J = 17.2, 1.6 Hz, 1 H), 3.49 (dt, J = 5.2, 1.6 Hz, 2 H).
© 2019. Thieme. All rights reserved. Synthesis 2019, 51, A–K

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Y. Song et al.
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Synthesis
13C NMR (100 MHz, CDCl3):  = 144.7, 139.8, 134.4, 132.8, 131.4,
131.1, 130.0 (q, JC–F = 32.4 Hz), 127.9, 127.2, 125.7 (q, JC–F = 3.7 Hz),
124.1 (q, JC–F = 270.5 Hz), 118.3, 118.1, 112.6, 51.3, 27.0.
HRMS (ESI): m/z [M + H]+ calcd for C20H16F3N4: 369.1322; found:
369.1331.
1H NMR (400 MHz, CDCl3):  = 8.86 (ddd, J = 8.4, 1.2, 0.4 Hz, 1 H), 7.95
(dd, J = 8.4, 1.2 Hz, 1 H), 7.91 (d, J = 8.8 Hz, 2 H), 7.78 (ddd, J = 8.4, 7.2,
1.2 Hz, 1 H), 7.65 (ddd, J = 8.4, 7.2, 1.2 Hz, 1 H), 7.60 (q, J = 1.2 Hz, 1 H),
7.08 (d, J = 8.8 Hz, 2 H), 3.89 (s, 3 H), 2.67 (d, J = 1.2 Hz, 3 H).
13C NMR (100 MHz, CDCl3):  = 159.6, 139.1, 134.0, 132.0, 130.0,
128.3, 127.8, 127.1, 125.4, 124.6, 124.4, 116.7, 114.6, 114.4, 55.6, 19.7.
HRMS (ESI): m/z [M + H]+ calcd for C18H16N3O: 290.1288; found:
4-({4-[4-(Trifluoromethyl)phenyl]-1H-1,2,3-triazol-1-yl}methyl)-
benzonitrile (5s)
290.1291.
Yield: 17.1 mg (13%); white solid; mp 178.8–180.8 °C; Rf = 0.21 (hex-
ane/EtOAc, 3:1).
1H NMR (400 MHz, CDCl3):  = 7.93 (d, J = 8.0 Hz, 2 H), 7.80 (s, 1 H),
7.73 (d, J = 8.4 Hz, 2 H), 7.70 (d, J = 8.0 Hz, 2 H), 7.41 (d, J = 8.4 Hz, 2
H), 5.67 (s, 2 H).
Funding Information
This research was supported by the National Research Foundation of
Korea (NRF-2018R1A5A2025286 and NRF-2017M3A9F5029066)
with grants funded by the Government of South Korea.
13C NMR (100 MHz, CDCl3):  = 147.5, 139.8, 133.8, 133.2, 130.5 (q,
N
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JC–F = 32.5 Hz), 128.6, 126.2 (q, JC–F = 3.8 Hz), 126.1, 124.2 (q, JC–F
=
270.5 Hz), 120.6, 118.2, 113.2, 53.8.
HRMS (ESI): m/z [M + Cl]– calcd for C17H11F3N4Cl: 363.0630; found:
363.0632.
Supporting Information
Supporting information for this article is available online at
https://doi.org/10.1055/s-0039-1691506.
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5-Allyl-1-(2-bromophenyl)-4-(4-methoxyphenyl)-1H-1,2,3-tri-
azole (4t)
To an oven-dried round-bottom flask with a side arm were added CuI
(91.4 mg, 480 mol) and NaNH2 (31.2 mg, 800 mol). A solution of 4-
methoxyphenylacetylene (1a) (52 L, 400 mol), 1-azido-2-bromo-
benzene (118.8 mg, 600 mol) and allyl iodide (146 L, 1.60 mmol) in
anhydrous toluene (1 mL) was added. The heterogeneous reaction
mixture was stirred at room temperature for 34 h. Upon completion
of the reaction, the mixture was filtered through a plug of Celite and
rinsed with CH2Cl2 (50 mL). The filtrate was concentrated and puri-
fied by column chromatography (hexane/EtOAc, 4:1) to afford triazole
4t.
References
(1) For a recent review, see: Rotstein, B. H.; Zaretsky, S.; Rai, V.;
Yudin, A. K. Chem. Rev. 2014, 114, 8323; and references cited
therein.
(2) (a) Bienaymé, H.; Hulme, C.; Oddon, G.; Schmitt, P. Chem. Eur. J.
2000, 6, 3321. (b) Ruijter, E.; Scheffelaar, R.; Orru, R. V. A. Angew.
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(4) (a) Kouznetsov, V. V.; Puerto Galvis, C. E. Tetrahedron 2018, 74,
773. (b) Liu, Y.-L.; Zhou, J. Synthesis 2015, 47, 1210. (c) Strecker,
A. Liebigs Ann. Chem. 1850, 75, 27.
Yield: 63.8 mg (43%); white solid; mp 106.3–108.3 °C; Rf = 0.21
(CH2Cl2/EtOAc, 50:1).
(5) Neochoritis, C. G.; Zhao, T.; Dömling, A. Chem. Rev. 2019, 119,
1970.
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8, 12069.
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(8) Adib, M.; Sheibani, E.; Bijanzadeh, H. R.; Zhu, L.-G. Tetrahedron
2008, 64, 10681.
(9) (a) Morris, J. C.; Chiche, J.; Grellier, C.; Lopez, M.; Bornaghi, L. F.;
Maresca, A.; Supuran, C. T.; Pouyssegur, J.; Poulsen, S.-A. J. Med.
Chem. 2011, 54, 6905. (b) Malnuit, V.; Duca, M.; Manout, A.;
Bougrin, K.; Benhida, R. Synlett 2009, 2123. (c) Joubert, N.;
Schinazib, R. F.; Agrofoglio, L. A. Tetrahedron 2005, 61, 11744.
(d) Barsoum, D. N.; Brassard, C. J.; Deeb, J. H. A.; Okashah, N.;
Sreenath, K.; Simmons, J. T.; Zhu, L. Synthesis 2013, 45, 2372.
(e) Li, L.; Li, R.; Zhu, A.; Zhang, G.; Zhang, L. Synlett 2011, 874.
(f) Smith, N. W.; Polenz, B. P.; Johnson, S. B.; Dzyuba, S. V. Tetra-
hedron Lett. 2010, 51, 550. (g) Li, L.; Zhang, G. G.; Zhu, A.; Zhang,
L. J. Org. Chem. 2008, 73, 3630. (h) Wu, Y.; Deng, J.; Li, Y.; Chen,
Q.-Y. Synthesis 2005, 1314.
1H NMR (400 MHz, CDCl3):  = 7.78–7.73 (m, 1 H), 7.75 (d, J = 8.8 Hz, 2
H), 7.51–7.39 (m, 3 H), 7.00 (d, J = 8.8 Hz, 2 H), 5.73 (ddt, J = 16.8, 10.0,
5.6 Hz, 1 H), 5.03 (dq, J = 10.0, 1.6 Hz, 1 H), 4.83 (dq, J = 16.8, 1.6 Hz, 1
H), 3.85 (s, 3 H), 3.47 (m, 2 H).
13C NMR (100 MHz, CDCl3):  = 159.7, 144.8, 135.9, 133.9, 132.5,
132.0, 131.7, 129.9, 128.7, 128.5, 123.8, 122.3, 118.0, 114.4, 55.6, 27.8.
HRMS (ESI): m/z [M + H]+ calcd for C18H17BrN3O: 370.055; found:
370.0553.
3-(4-Methoxyphenyl)-5-methyl-[1,2,3]triazolo[1,5-a]quinoline
(6t)
To an oven-dried round-bottom flask with a side arm were added pal-
ladium acetate (7.63 mg, 0.034 mmol), tetrabutylammonium chloride
(94.5 mg, 0.34 mmol) and potassium acetate (92.3 mg, 0.94 mmol). A
solution of 4t (63.8 mg, 0.17 mmol) in anhydrous toluene (1 mL) was
then added and the heterogeneous reaction mixture was stirred at
110 °C for 40 min. Upon completion of the reaction, the mixture was
concentrated in vacuo and purified by medium pressure liquid chro-
matography on silica gel (hexane/EtOAc, 3.5:1) to afford fused tricycle
6t.
(10) Chen, Z.; Liu, Z.; Cao, G.; Li, H.; Ren, H. Adv. Synth. Catal. 2017,
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2696.
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Expert Opin. Pharmacother. 2007, 8, 1931.
Yield: 29.2 mg (59%); pale yellow solid; mp 155.4–157.4 °C; Rf = 0.20
(hexane/EtOAc, 5:1).
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83, 141.
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K
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Paper
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X.; Zhang, C.; Zhu, A.; Fan, X.; Chen, C.; Zhang, G. Tetrahedron
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(20) For recent multicomponent CuAAC reactions, see: (a) Qureshi,
Z.; Kim, J. Y.; Bruun, T.; Lam, H.; Lautens, M. ACS Catal. 2016, 6,
4946. (b) Yamamoto, K.; Bruun, T.; Kim, J. Y.; Zhang, L.; Lautens,
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Chem. Rec. 2016, 16, 1501. (b) Singh, M. S.; Chowdhury, S.;
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© 2019. Thieme. All rights reserved. Synthesis 2019, 51, A–K