One-pot three component synthesis of 5-allyl-1,2,3-triazoles using copper(i) acetylides

Article abstract of DOI:10.1039/c7ra12889d

One-pot three-component reactions using copper(i) acetylide, azide, allyl iodide, and NaOH have been developed. The reactions proceed smoothly at room temperature to afford 5-allyl-1,2,3-triazoles, which can be further transformed into a variety of 1,2,3-triazole-fused bi-/tricyclic scaffolds. This method offers the most efficient, convenient, and practical route towards useful polycyclic scaffolds in moderate to excellent yields.

Full text of DOI:10.1039/c7ra12889d

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One-pot three component synthesis of 5-allyl-
1,2,3-triazoles using copper(I) acetylides†
Cite this: RSC Adv., 2018, 8, 2759
Parigi Raghavendar Reddy, Lianji Cui and Jae-Sang Ryu
*
One-pot three-component reactions using copper(I) acetylide, azide, allyl iodide, and NaOH have been
developed. The reactions proceed smoothly at room temperature to afford 5-allyl-1,2,3-triazoles, which
can be further transformed into a variety of 1,2,3-triazole-fused bi-/tricyclic scaffolds. This method offers
the most efficient, convenient, and practical route towards useful polycyclic scaffolds in moderate to
excellent yields.
Received 29th November 2017
Accepted 3rd January 2018
DOI: 10.1039/c7ra12889d
rsc.li/rsc-advances
presence of terminal alkyne substrates or protic polar solvents.
Recently, this drawback was smartly overcome by using cop-
Introduction
1
1
,2,3-Triazoles are very important heterocycles in chemistry per(I) acetylide instead of a terminal alkyne in the halogena-
2
12
13
and biology. Synthetic molecules containing a 1,2,3-triazole tion and acylation, by Y. Hu's group.
scaffold exhibit diverse biological activities, which have drawn
Copper(I) acetylides are highly crystalline polymeric
14
the attention of medicinal chemists in the drug discovery eld. complexes, (RC^CCu)
Currently, there are several 1,2,3-triazole-containing medicines base and heat so they can be kept on the shelf for several
on the market, and the number of potential pharmaceuticals months without the quality deteriorating. In the absence of
.
They are stable to air, water, acid/
n
15
3
based on these scaffolds keeps increasing. Beyond the drug exogenous ligands or additives, copper(I) phenylacetylide,
13
market, 1,2,3-triazoles are utilized in a variety of areas including PhC^CCu, is not effective under typical CuAAC conditions: It
4
5
bioconjugation, polymer and materials science, and related did not undergo a cycloaddition with azide and did not provide
areas including supramolecular chemistry, DNA labeling and a 1,2,3-triazole product. However, when it was combined with
6
7
8
9
oligonucleotide synthesis. Such wide applications of 1,2,3-tri- both azide and acyl chloride, it quickly provided 5-acyl-1,2,3-
13
azoles are due to their facile synthesis through Cu(I)-catalyzed triazoles. The presence of acyl chloride accelerated the cyclo-
13
azide–alkyne cycloaddition (CuAAC), so-called ‘click chemistry’. addition of copper(I) phenylacetylide and azide.
This
Since it was rst introduced by Sharpless and co-workers, intriguing result motivated us to investigate one-pot three-
CuAAC has been rapidly adopted as a universal coupling component reactions using copper(I) phenylacetylide. We are
process. However, in terms of substrate scope, CuAAC is particularly interested in 5-allyl-1,2,3-triazoles as precursors for
restricted to terminal alkynes, leading to 1,4-disubstituted 1,2,3- the development of new anticancer agents. However, efficient
triazoles, and the one-pot synthetic methods for the fully
10
substituted 1,2,3-triazoles are still relatively few.
In one-pot three-component reactions used to obtain 5-halo
+
1
,2,3-triazoles, an electrophile X (X ¼ Cl, Br, and I) is added
+
into the CuAAC reaction to trap X with an in situ generated 5-
11
copper(I) 1,2,3-triazole intermediate A (Scheme 1). However,
the result is usually the formation of a mixture of the desired 5-
substituted 1,2,3-triazole 3 and the byproduct 1,4-disubstituted
1
,2,3-triazole 4, which is generated from a competitive proton-
12
ation of the 5-copper(I) 1,2,3-triazole intermediate A. This
competitive protonation is accelerated by a proton source,
provided from the terminal alkyne substrate in the normal
CuAAC. Therefore, this problem cannot be avoided in the
College of Pharmacy & Graduate School of Pharmaceutical Sciences, Ewha Womans
University, 52 Ewhayeodae-gil, Seodaemun-Gu, Seoul 03760, Republic of Korea.
E-mail: ryuj@ewha.ac.kr
1
13
Scheme 1 Cu(I)-catalyzed azide–alkyne cycloaddition methods for
†
Electronic supplementary information (ESI) available: Copies of H and
C
the synthesis of 5-substituted 1,2,3-triazoles.
NMR spectra for 3a–z and 6v–z. See DOI: 10.1039/c7ra12889d
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10a,b
methods for the synthesis of 5-allyl-1,2,3-triazoles are rare.
decreased to 36% when the amount of allyl iodide increased to 4
Interestingly, copper(I) acetylide has never been used directly as equivalents (entry 2). The use of Et N appeared to decompose
3
a substrate for the synthesis of 5-allyl-1,2,3-triazoles, although it the stable polymeric complex with the structure [(PhC^CCu)2]n
is known to be a key intermediate. Herein, we report one-pot into a lower polymeric or a more reactive monomeric structure.
three-component reactions for the synthesis of 5-allyl-1,2,3- As soon as Et
3
N was added, the heterogeneous reaction mixture
became clear and rapidly yielded both an undesired byproduct
as well as the desired product. However, replacing Et N with
pyridine, quinine, or inorganic bases such as Na PO , K PO
Na CO , K CO , Cs CO , NaOH, or KOH did not change the
triazoles from copper(I) acetylides.
3
3
4
3
4
,
Results and discussion
2
3
2
3
2
3
heterogeneity of the reaction. The copper(I) phenylacetylide (1a)
To assess the feasibility of the tandem CuAAC–allylation reac-
tion, we started to investigate one-pot three component reac-
tions in the presence of copper(I) phenylacetylide (1a), 4-
cyanobenzyl azide (2a), allyl iodide, and base (Table 1). In
preliminary screening of reaction conditions, we obtained the
desired product 5-allyl-1,2,3-triazole 3a and a byproduct enyne
remained suspended in CH Cl , which not only slowed reaction
2
2
progress but also signicantly reduced byproduct formation.
The reaction using quinine increased the yield of desired
product 3a up to 74%, but interestingly 2% of a protonated
byproduct 4a was isolated instead of the allyl alkyne byproduct
5a (entry 3). The reaction using pyridine did not signicantly
5a with 47% and 42% yield respectively aer 4 h at room
increase the yield compared to the reaction of Et N. However,
3
temperature when 1.5 equivalents of cyanobenzyl azide (2a), 3
the formation of byproducts 4a and 5a was not observed (entry
4). Similarly, the reactions using inorganic bases also generated
equivalents of allyl iodide, and 2 equivalents of Et N were
3
employed (entry 1). The yield of the desired product 3a
increased to 60% and the yield of the byproduct enyne 5a
5
-allyl-1,2,3-triazole 3a as a sole product (entries 5–11).
Hydroxide bases (KOH, NaOH: entries 10 and 11) are better than
phosphate bases (Na PO , K PO : entries 5 and 6) or carbonate
bases (Na CO , K CO , Cs CO : entries 7–9) in terms of yield.
Among bases used, the best result was obtained with NaOH
84%, entry 10). It appears the use of base is essential for the
3
4
3
4
2
3
2
3
2
3
a
Table 1 Optimization of reaction conditions
(
reaction. Without a base, 5-allyl-1,2,3-triazole 3a was isolated
with only a moderate yield (52%, entry 12). The role of NaOH is
not clear, and it is still under investigation. It is also noteworthy
that the byproduct 1,4-disubstituted 1,2,3-triazole 4a, which is
generated from a competitive protonation of 5-copper(I) 1,2,3-
triazole intermediate A, was not detected in reactions using
copper(I) phenylacetylide (1a) with the exception of quinine.
Next, we investigated the solvent effect on the yield of Cu(I)-
catalyzed azide–alkyne cycloaddition–allylation reactions of
copper(I) acetylides in the presence of NaOH. The reactions were
effective in various solvents including CH Cl , dioxane, THF,
2
2
3
toluene, and CH CN (entries 13–16). Considering yield of the
b
Yield (%)
product, toluene (entry 15) was the best solvent for the reaction.
On the basis of Table 1, we chose NaOH as a base and the
relatively nonpolar solvent, toluene, for further study.
Entry
Base
Solvent
Time (h)
3a
4a
5a
c
1
Et
Et
Quinine
Pyridine
3
N
N
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
2
2
2
2
2
2
2
2
2
2
2
2
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
2
2
2
2
2
2
2
2
2
2
2
2
4
4
47
60
74
63
47
45
62
71
67
84
83
52
89
85
94
68
0
0
2
0
0
0
0
0
0
0
0
0
0
0
0
0
42
36
0
0
0
0
0
0
0
0
0
0
0
0
0
0
Once we had established optimal reaction conditions, we
examined the scope of one-pot three-component reactions
2
3
4
5
6
7
8
9
3
24
24
24
24
24
21
24
24
24
24
24
24
24
24
(Table 2). We applied the copper(I) acetylide system to various
azides in toluene at room temperature. All reactions using
copper(I) acetylides in Table 2 smoothly furnished 5-allyl-1,4-
disubstituted 1,2,3-triazoles 3b–u and a trace amount of enyne
byproduct 5b–u at room temperature. As anticipated, the 1,4-
disubstituted 1,2,3-triazoles 4, which are unavoidable in the
typical CuAAC reactions, were not detected. First, we explored
the reaction scope with benzyl azides. The reaction yields were
independent of the electronic nature of azides. Substrates 2c–e
bearing electron-donating substituents and substrates 2f–h
bearing electron-withdrawing substituents underwent the one-
pot three-component reactions very smoothly, and provided
the corresponding 5-allyl-1,4-disubstituted 1,2,3-triazoles 3c–h
at room temperature, in good to excellent yields (85–97%). The
reaction scope was not limited to only benzyl azides, but was
Na
PO
Na CO
CO
Cs CO
3
PO
4
K
3
4
2
3
K
2
3
2
3
1
1
1
1
1
1
1
0
1
2
3
4
5
6
NaOH
KOH
—
NaOH
NaOH
NaOH
NaOH
Dioxane
THF
Toluene
CH
3
CN
a
Reaction conditions: 1a (65.8 mg, 400 mmol), 2a (94.9 mg, 600 mmol),
base (800 mmol), allyl iodide (146 mL, 1.60 mmol), solvent (1 mL). All
reactions were carried out under Ar. Isolated yields. 1.20 mmol of
allyl iodide was used.
b
c
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Table 2 Cu(I)-catalyzed azide–alkyne cycloaddition–allylation reac- Table
3
Synthesis of fused 1,2,3-triazoles using Cu(I)-catalyzed
a
a
tions under optimized conditions
azide–alkyne cycloaddition–allylation reactions and ring closing
b
metathesis
c
c
Entry
1
Yield of 3
Yield of 6
2
3
4
5
a
Reaction conditions: 1a (65.8 mg, 400 mmol), 2 (600 mmol), NaOH
(
32.0 mg, 800 mmol), allyl iodide (146 mL, 1.60 mmol), toluene (1 mL).
b
All reactions were carried out under Ar. Reaction conditions: 3 (200
st
mmol), Grubbs' 1 generation catalyst (5 mol%), CH
2
Cl
2
(9.3 mL).
c
d
e
Isolated yields. 180 mmol of 3 was used. 150 mmol of 3 and
nd
Hoveyda-Grubbs' 2 generation catalyst (5 mol%) were used.
method is not limited to the use of simple allyl iodide. Other
various substituted allyl iodides could be used for one-pot three-
component reactions, and produced the corresponding 5-allyl-
1
,4-disubstituted 1,2,3-triazoles 3q–t with yields in the
a
Reaction conditions: 1 (400 mmol), 2 (600 mmol), NaOH (32.0 mg, 800 range of 53–90%. Delightfully, the reaction scope was also
mmol), allyl iodide (1.60 mmol), toluene (1 mL). All reactions were
carried out under Ar.
expandable to copper(I) alkylacetylide, which afforded 4-alkyl
1,2,3-triazole 3u.
Finally, we studied further transformations of 5-allyl-1,4-
disubstituted 1,2,3-triazoles into various fused polyhetero-
cycles in order to demonstrate the synthetic utility of the 5-allyl-
also compatible with aryl azides 2i–k and aliphatic azide 2l. In
addition, a variety of copper(I) arylacetylides were also tested.
Regardless of the electronic inuence of substituents on cop-
per(I) arylacetylides, desired products 3m–p were obtained in
moderate to good yields (54–75%). It is worth noting that this
1,4-disubstituted 1,2,3-triazoles as versatile building blocks
(Table 3). The alkene-tethered 5-allyl-1,2,3-triazoles 3v–x were
synthesized based on Cu(I)-catalyzed azide–alkyne cycloaddi-
tion–allylation reactions of copper(I) acetylides in good yields
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(entries 1–3, 65–80%) and these were converted into fused 1,2,3- steel cannula. TLC was performed on 0.25 mm E. Merck silica
triazoles 6v–x by ring-closing metathesis reactions, which were gel 60 F254 plates and visualized under UV light (254 nm) or by
effective for the synthesis of 7-, 8- and 9-membered fused 1,2,3- staining with cerium ammonium molybdenate (CAM), potas-
triazoles with good yields (entries 1–3, 65–87%). The trans- sium permanganate (KMnO ) or p-anisaldehyde. Flash chro-
4
formations were also applicable to substrates bearing styrene- matography was performed on E. Merck 230–400 mesh silica gel
type alkenes 3y and 3z. The ring-closing metathesis of 3y and 60. Reagents were purchased from commercial suppliers, and
3z proceeded smoothly to afford fused tricyclic 1,2,3-triazoles used without further purication unless otherwise noted.
(
entries 4 and 5, 70–92%). Solvents were distilled from proper drying agents (CaH or Na
2
16
On the basis of previous mechanistic studies and our own wire) under Ar atmosphere at 760 mmHg. NMR spectra were
ꢀ
observation, we speculate that Cu(I) acetylide 1 coordinates with recorded at 24 C. Chemical shis are expressed in ppm relative
the azide 2 to form the intermediate I-1 and following cycliza- to TMS ( H, 0 ppm), CDCl ( H, 7.26 ppm; C, 77.2 ppm), and
1
1
13
3
1
9
tion leads to the metallocycle intermediate I-2. The 6-membered C H F ( F, ꢁ113.15 ppm); coupling constants are expressed
6
5
Cu(I)-intermediate contracts to the Cu(I)-1,2,3-triazole interme- in Hz. High resolution mass spectra (HRMS) were obtained by
diate I-3, which is readily trapped by allyl iodide to yield the electrospray ionization (ESI, TOF) or electron ionization (EI,
desired 5-allyl-1,4-disubstituted 1,2,3-triazole 3 (Scheme 2).
magnetic sector). Infrared spectra were recorded with peaks
ꢁ
1
reported in cm
.
General procedure for the Cu(I)-catalyzed azide–alkyne
cycloaddition–allylation reactions
Copper(I) acetylide (400 mmol) was placed in a 25 mL one-arm
roundbottom ask. A solution of azide (600 mmol) in anhy-
drous toluene (1 mL), allyl iodide (268 mg, 1.60 mmol) and
NaOH (32.0 mg, 800 mmol) were sequentially added to the
reaction mixture. The resulting suspension was stirred at room
temperature for 24 h or 48 h as indicated in Table 1. The
mixture was ltered and washed with CH
2 2
Cl (20 mL). To
scavenge Cu, polymer-bound ethylenediaminetriacetic acid
ꢁ1
acetamide (3.0–4.0 mmol g , 200 mg) was added to the ltrate,
and stirred for 2 h. The polymer was ltered off and the ltrate
was concentrated by rotary evaporation. Purication of crude
residue by column chromatography yielded 3a–z. The reaction
of 3y was carried out for 3 days at room temperature.
Scheme 2 Plausible mechanism of Cu(I)-mediated one-pot three
component synthesis of 5-allyl-1,2,3-triazoles.
4
-((5-Allyl-4-phenyl-1H-1,2,3-triazol-1-yl)methyl)benzonitrile
3a). TLC: R 0.25 (2 : 1 hexane/EtOAc). White solid (113 mg,
4%). Mp ¼ 113–115 C. H NMR (400 MHz, CDCl
Conclusions
(
9
(
f
ꢀ
1
3
): d 7.68–7.63
In conclusion, we have developed a novel one-pot three
component reaction method for the synthesis of 5-allyl-1,4-
disubstituted 1,2,3-triazoles from copper(I) acetylides. The 5-
allyl-1,4-disubstituted 1,2,3-triazoles were produced via 1,3-
dipolar cycloaddition followed by in situ trapping of the C(sp )–
Cu intermediate. The byproduct 1,4-disubstituted 1,2,3-triazole
m, 4H), 7.45–7.41 (m, 2H), 7.38–7.34 (m, 1H), 7.28 (d, J ¼
8
1
.4 Hz, 2H), 5.83 (m, 1H), 5.57 (s, 2H), 5.15 (dd, J ¼ 10.4 Hz,
13
.2 Hz, 1H), 4.88 (dd, J ¼ 16.8 Hz, 1.2 Hz, 1H), 3.45 (m, 2H).
): d 146.2, 140.3, 132.9, 132.1, 131.0,
30.4, 128.9, 128.3, 128.0, 127.3, 118.3, 118.2, 112.6, 51.4, 27.1.
C
NMR (100 MHz, CDCl
3
2
1
+
HRMS (ESI) m/z calculated for C19
found 301.1451. IR (KBr lm): n 3061, 2229, 1639, 1506, 920,
20, 777, 699 cm
5
2 : 1 hexane/EtOAc). Pale yellow liquid (97.9 mg, 89%). H NMR
400 MHz, CDCl ): d 7.70–7.67 (m, 2H), 7.44–7.40 (m, 2H), 7.36–
.30 (m, 4H), 7.20–7.18 (m, 2H), 5.83 (m, 1H), 5.54 (s, 2H), 5.15
17 4
H N [M + H] 301.1448,
4, which is generated from a competitive protonation of 5-
copper(I) 1,2,3-triazole intermediate A, was not isolated. The
present method was successfully applied to achieve production
of synthetically useful heterocycles. This domino reaction is
characterized by mild conditions and no protonated byproduct
formation, and allows for the efficient construction of func-
tionalized fused polycyclic 1,2,3-triazoles.
ꢁ1
8
.
-Allyl-1-benzyl-4-phenyl-1H-1,2,3-triazole (3b). TLC: R 0.52
f
1
(
(
3
7
(
dm, J ¼ 12.0 Hz, 1H), 4.92 (dm, J ¼ 15.2 Hz, 1H), 3.45 (m, 2H).
1
3
C NMR (100 MHz, CDCl
3
): d 146.0, 135.1, 132.4, 131.5, 130.4,
1
29.1, 128.8, 128.5, 128.0, 127.3, 117.9, 52.1, 27.1. HRMS (ESI)
Experimental
General
+
m/z calculated for C18
IR (KBr lm): n 3063, 3033, 1639, 1608, 1496, 918, 800, 764 cm
5-Allyl-1-(4-methylbenzyl)-4-phenyl-1H-1,2,3-triazole (3c).
H
18
N
3
[M + H] 276.1495, found 276.1501.
ꢁ1
All reactions were performed in oven-dried glassware tted with
glass stoppers under positive pressure of Ar with magnetic TLC: R 0.55 (2 : 1 hexane/EtOAc). White solid (97.9 mg, 85%).
f
ꢀ
1
stirring, unless otherwise noted. Air- and moisture-sensitive Mp ¼ 42–44 C. H NMR (400 MHz, CDCl
3
): d 7.69–7.66 (m,
liquids and solutions were transferred via syringe or stainless- 2H), 7.44–7.39 (m, 2H), 7.36–7.31 (m, 1H), 7.14 (d, J ¼ 8.0 Hz,
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2
H), 7.09 (d, J ¼ 8.0 Hz, 2H), 5.84 (m, 1H), 5.49 (s, 2H), 5.17 7.33 (m, 3H), 5.84 (m, 1H), 5.61 (s, 2H), 5.14 (dm, J ¼ 12.0 Hz,
13
(
dq, J ¼ 10.4 Hz, 2.0 Hz, 1H), 4.93 (dq, J ¼ 17.2 Hz, 2.0 Hz, 1H), 1H), 4.89 (dm, J ¼ 17.2 Hz, 1H), 3.47 (m, 2H). C NMR (100
13
3
1
1
.45 (m, 2H), 2.33 (s, 3H). C NMR (100 MHz, CDCl ): d 146.0, MHz, CDCl ): d 148.0, 146.2, 142.2, 132.1, 131.0, 130.5, 128.9,
3 3
38.3, 132.5, 132.1, 131.5, 130.4, 129.8, 128.8, 128.0, 127.3, 128.3, 128.2, 127.3, 124.3, 118.2, 51.1, 27.1. HRMS (ESI) m/z
+
17.9, 52.0, 27.2, 21.3. HRMS (ESI) m/z calculated for calculated for C18
H
17
N
4
O
2
[M + H] 321.1346, found 321.1348.
+
ꢁ1
C
3
19
H
20
N
3
[M + H] 290.1652, found 290.1657. IR (KBr lm): n IR (KBr lm): n 3081, 1608, 1520, 1495, 1347, 805, 734 cm
.
ꢁ1
056, 3031, 1639, 1495, 1360, 919, 792, 716 cm
.
5-Allyl-4-phenyl-1-(p-tolyl)-1H-1,2,3-triazole (3i). TLC: R
f
0.72
5
-Allyl-1-(4-methoxybenzyl)-4-phenyl-1H-1,2,3-triazole (3d). (2 : 1 hexane/EtOAc). White solid (98.3 mg, 89%). Mp ¼ 106–
ꢀ
1
TLC: R
f
0.35 (2 : 1 hexane/EtOAc). Pale yellow liquid (107 mg, 108 C. H NMR (400 MHz, CDCl
3
): d 7.82 (d, J ¼ 8.4 Hz, 2H),
1
8
(
8%). H NMR (400 MHz, CDCl ): d 7.68–7.65 (m, 2H), 7.43–7.39 7.48–4.37 (m, 5H), 7.33 (d, J ¼ 8.4 Hz, 2H), 5.91 (m, 1H), 5.19 (d, J
3
m, 2H), 7.35–7.31 (m, 1H), 7.15 (dm, J ¼ 9.6 Hz, 2H), 6.86 (dm, J ¼ 9.6 Hz, 1H), 4.93 (d, J ¼ 17.2 Hz, 1H), 3.57 (dm, J ¼ 4.0 Hz,
1
3
¼
9.6 Hz, 2H), 5.84 (m, 1H), 5.46 (s, 2H), 5.16 (dq, J ¼ 10.4 Hz, 2H), 2.45 (s, 3H). C NMR (100 MHz, CDCl ): d 145.4, 140.1,
3
2
.0 Hz, 1H), 4.92 (dq, J ¼ 16.8 Hz, 2.0 Hz, 1H), 3.78 (s, 3H), 3.46 134.1, 133.4, 131.4, 131.1, 130.1, 128.9, 128.1, 127.3, 125.5,
1
3
(
m, 2H). C NMR (100 MHz, CDCl
3
): d 159.7, 146.0, 132.5, 131.5, 118.2, 27.7, 21.4. HRMS (ESI) m/z calculated for C18
H
18
N
3
[M +
+
1
2
3
1
30.3, 128.9, 128.8, 128.0, 127.3, 127.1, 117.8, 114.5, 55.4, 51.7, H] 276.1495, found 276.1501. IR (KBr lm): n 2919, 1517, 992,
7.1. HRMS (ESI) m/z calculated for C19
06.1601, found 306.1595. IR (KBr lm): n 3063, 3005, 1639,
514, 1250, 1032, 921, 825, 715 cm
+
ꢁ1
H
20
N
3
O [M + H]
934, 710 cm .
5-Allyl-1-(4-methoxyphenyl)-4-phenyl-1H-1,2,3-triazole (3j).
ꢁ
1
TLC: R 0.37 (3 : 1 hexane/EtOAc). Light brown solid (76.0 mg,
f
ꢀ
1
5
-Allyl-1-(3,5-dimethoxybenzyl)-4-phenyl-1H-1,2,3-triazole (3e). 65%). Mp ¼ 97–99 C. H NMR (400 MHz, CDCl ): d 7.81 (d, J ¼
3
TLC: R 0.37 (2 : 1 hexane/EtOAc). White solid (126 mg, 94%). Mp 7.2 Hz, 2H), 7.47–7.34 (m, 5H), 7.03 (d, J ¼ 9.2 Hz, 2H), 5.91 (m,
f
ꢀ
1
¼
80–82 C. H NMR (400 MHz, CDCl
3
): d 7.64–7.61 (m, 2H), 7.38– 1H), 5.19 (dd, J ¼ 10.0 Hz, 1.2 Hz, 1H), 4.92 (dd, J ¼ 17.6 Hz,
13
7
.34 (m, 2H), 7.27 (tt, J ¼ 6.4 Hz, 1.2 Hz, 1H), 6.33 (t, J ¼ 2.0 Hz, 1.2 Hz, 1H), 3.88 (s, 3H), 3.56 (m, 2H). C NMR (100 MHz,
1
H), 6.27 (d, J ¼ 2.0 Hz, 2H), 5.79 (m, 1H), 5.39 (s, 2H), 5.10 (dq, J CDCl
3
): d 160.6, 133.4, 131.4, 129.4, 128.9, 128.8, 128.0, 127.2,
¼
12.0 Hz, 2.0 Hz, 1H), 4.88 (dq, J ¼ 18.8 Hz, 2.0 Hz, 1H), 3.67 (s, 127.1, 118.1, 114.7, 114.6, 55.8, 27.7. HRMS (ESI) m/z calcu-
1
3
+
6
1
5
H), 3.40 (m, 2H). C NMR (100 MHz, CDCl
3
18 3
): d 161.4, 145.9, lated for C18H N O [M + H] 292.1444, found 292.1449. IR
ꢁ
1
37.3, 132.4, 131.4, 130.5, 128.7, 127.9, 127.2, 117.8, 105.3, 100.0, (KBr lm): n 3081, 1639, 1508, 1260, 1030, 835, 714 cm
.
5.5, 52.1, 27.1. HRMS (ESI) m/z calculated for C H N O [M + 5-Allyl-1-(4-uorophenyl)-4-phenyl-1H-1,2,3-triazole (3k). TLC:
2
0
22 3 2
+
H] 336.1707, found 336.1708. IR (KBr lm): n 3003, 2938, 1598, R 0.45 (2 : 1 hexane/EtOAc). Light yellow solid (70.0 mg, 63%).
f
ꢁ1
ꢀ
1
1
206, 1066, 921, 777 cm
.
Mp ¼ 121–123 C. H NMR (400 MHz, CDCl
3
): d 7.81 (d, J ¼
5-Allyl-1-(4-uorobenzyl)-4-phenyl-1H-1,2,3-triazole (3f). TLC: 7.2 Hz, 2H), 7.54–7.48 (m, 2H), 7.48–7.44 (m, 2H), 7.40–7.36 (m,
1
R
f
0.45 (2 : 1 hexane/EtOAc). Pale yellow liquid (114 mg, 97%). H 1H), 7.24 (t, J ¼ 8.4 Hz, 2H), 5.92 (m, 1H), 5.21 (dd, J ¼ 10.4 Hz,
13
NMR (400 MHz, CDCl
3
): d 7.68–7.66 (m, 2H), 7.44–7.40 (m, 2H), 1.2 Hz, 1H), 4.92 (dd, J ¼ 17.2 Hz, 1.2 Hz, 1H), 3.57 (m, 2H).
.34 (tt, J ¼ 6.4 Hz, 1.2 Hz, 1H), 7.20 (dd, J ¼ 8.8 Hz, 5.6 Hz, 2H), NMR (100 MHz, CDCl ): d 163.3 (d, JC–F ¼ 249.2 Hz), 145.6, 133.2,
.03 (t, J ¼ 8.8 Hz, 2H), 5.84 (m, 1H), 5.50 (s, 2H), 5.16 (dm, J ¼ 132.6 (d, JC–F ¼ 3.1 Hz), 131.2 (d, J ¼ 6.2 Hz), 128.9, 128.3, 127.7
C
7
7
1
(
1
1
(
C
3
3
C–F
1
3
0.0 Hz, 1H), 4.91 (dm, J ¼ 16.4 Hz, 1H), 3.45 (m, 2H). C NMR (d, J
¼ 9.3 Hz), 127.3, 126.1, 118.4, 116.7 (d, J
¼ 22.5 Hz),
C–F
C–F
1
9
100 MHz, CDCl ): d 162.8 (d, J ¼ 246.0 Hz), 146.1, 132.3, 131.3, 27.7. F NMR (376 MHz, CDCl ): d ꢁ110.9. HRMS (EI) m/z
3
C–F
3
+
30.9 (d, JC–F ¼ 3.1 Hz), 130.3, 129.3 (d, JC–F ¼ 7.8 Hz), 128.9, calculated for C17
H14FN
3
[M] 279.1171, found 279.1172. IR (KBr
1
9
ꢁ1
28.1, 127.3, 118.0, 116.1 (d, JC–F ¼ 21.7 Hz), 51.4, 27.1. F NMR lm): n 3082, 1514, 1244, 992, 846, 721, 701 cm
.
376 MHz, CDCl
3
): d ꢁ113.1. HRMS (ESI) m/z calculated for
5-Allyl-1-octyl-4-phenyl-1H-1,2,3-triazole (3l). TLC: R
f
0.65
+
1
18 3
H17FN [M + H] 294.1401, found 294.1405. IR (KBr lm): n (2 : 1 hexane/EtOAc). Pale yellow liquid (107 mg, 90%). H NMR
ꢁ
1
066, 3011, 1640, 1512, 1015, 920, 715, 698 cm
-Allyl-4-phenyl-1-(4-(triuoromethyl)benzyl)-1H-1,2,3-triazole 8.4 Hz, 2H), 7.35–7.31 (m, 1H), 5.96 (m, 1H), 5.20 (dd, J ¼
3g). TLC: R 0.47 (2 : 1 hexane/EtOAc). Light yellow solid (128 mg, 10.4 Hz, 1.2 Hz, 1H), 4.96 (dd, J ¼ 16.8 Hz, 1.2 Hz, 1H), 4.23 (t, J
.
(400 MHz, CDCl
3
): d 7.68 (dm, J ¼ 8.4 Hz, 2H), 7.42 (tm, J ¼
5
(
f
ꢀ
1
9
8
7
4
3%). Mp ¼ 63–65 C. H NMR (400 MHz, CDCl ): d 7.69 (d, J ¼ ¼ 7.2 Hz, 2H), 3.58 (m, 2H), 1.92 (quin, J ¼ 7.2 Hz, 2H), 1.40–
3
13
.8 Hz, 2H), 7.59 (d, J ¼ 8.0 Hz, 2H), 7.42 (t, J ¼ 8.0 Hz, 2H), 7.36– 1.26 (m, 10H), 0.87 (t, J ¼ 7.2 Hz, 3H). C NMR (100 MHz,
.29 (m, 3H), 5.84 (m, 1H), 5.57 (s, 2H), 5.15 (d, J ¼ 10.0 Hz, 1H), CDCl ): d 145.3, 132.9, 131.7, 129.9, 128.8, 127.9, 127.3, 117.8,
.90 (d, J ¼ 17.2 Hz, 1H), 3.45 (dm, J ¼ 3.2 Hz, 2H). C NMR (100 48.3, 31.8, 30.3, 29.3, 29.2, 27.2, 26.8, 22.7, 14.2. HRMS (ESI) m/z
3
1
3
+
MHz, CDCl
3
): d 146.1, 139.1 (q, JC–F ¼ 1.5 Hz), 132.1, 131.2, 130.8 calculated for C19
28 3
H N [M + H] 298.2278, found 298.2278. IR
ꢁ1
(
q, JC–F ¼ 32.5 Hz), 130.5, 128.8, 128.1, 127.6, 127.3, 126.1 (q, JC–F (KBr lm): n 2954, 2926, 1640, 1495, 1361, 765, 698 cm
.
1
9
¼
3.9 Hz), 124.0 (q, J
¼ 270.9 Hz), 118.0, 51.4, 27.1. F NMR
5-Allyl-1-benzyl-4-(4-uorophenyl)-1H-1,2,3-triazole (3m).
C–F
(
376 MHz, CDCl ): d ꢁ63.1. HRMS (ESI) m/z calculated for TLC: R 0.6 (3 : 1 hexane/EtOAc). White solid (81.6 mg, 70%).
3
f
+
ꢀ
1
C H N F [M + H] 344.1369, found 344.1374. IR (KBr lm): n Mp ¼ 79–81 C. H NMR (400 MHz, CDCl ): d 7.65 (dd, J ¼
1
9
17
3
3
3
ꢁ
1
3
064, 1640, 1496, 1125, 824, 779, 699 cm
.
8.8 Hz, 5.6 Hz, 2H), 7.36–7.30 (m, 3H), 7.20–7.18 (m, 2H), 7.11
5
-Allyl-1-(4-nitrobenzyl)-4-phenyl-1H-1,2,3-triazole (3h). TLC: (t, J ¼ 8.8 Hz, 2H), 5.81 (m, 1H), 5.53 (s, 2H), 5.15 (dd, J ¼
R
f
0.35 (2 : 1 hexane/EtOAc). Light yellow solid (110 mg, 86%). 10.4 Hz, 1.2 Hz, 1H), 4.90 (dd, J ¼ 17.2 Hz, 1.2 Hz, 1H), 3.42
ꢀ
1
1
3
Mp ¼ 93–95 C. H NMR (400 MHz, CDCl
3
): d 8.19 (dm, J ¼ (m, 2H). C NMR (100 MHz, CDCl ): d 162.7 (d, JC–F ¼ 245.3
3
8
.8 Hz, 2H), 7.67 (dm, J ¼ 8.8 Hz, 2H), 7.44–7.41 (m, 2H), 7.37– Hz), 145.2, 135.0, 132.2, 130.2, 129.2, 129.1 (d, JC–F ¼ 8.5 Hz),
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+
1
2
28.5, 127.6 (d, JC–F ¼ 3.1 Hz), 127.4, 118.0, 115.8 (d, JC–F
¼
[M + H] 352.1808, found 352.1807. IR (KBr lm): n 3058, 3032,
1
9
ꢁ1
0.9 Hz), 52.2, 27.1. F NMR (376 MHz, CDCl ): d ꢁ110.9. 1954, 1628 cm
.
3
+
HRMS (ESI) m/z calculated for C H FN [M + H] 294.1401,
1-Benzyl-5-(3-methylbut-2-en-1-yl)-4-phenyl-1H-1,2,3-triazole
1
8
17
3
found 294.1404. IR (KBr lm): n 3081, 1640, 1510, 1224, 992, (3s). TLC: R 0.37 (2 : 1 hexane/EtOAc). White solid (89.0 mg,
f
ꢁ
1
ꢀ
1
8
41, 764, 698 cm
-Allyl-1-benzyl-4-(2-chlorophenyl)-1H-1,2,3-triazole (3n). 7.2 Hz, 2H), 7.42 (t, J ¼ 7.2 Hz, 2H), 7.38–7.28 (m, 4H), 7.16 (d, J
TLC: R
0.37 (2 : 1 hexane/EtOAc). Pale yellow liquid (66.7 mg, ¼ 6.4 Hz, 2H), 5.54 (s, 2H), 4.93 (m, 1H), 3.41 (d, J ¼ 6.4 Hz, 2H),
.
73%). Mp ¼ 86–88 C. H NMR (400 MHz, CDCl
3
): d 7.67 (d, J ¼
5
f
1
13
5
7
5
1
1
1
4%). H NMR (400 MHz, CDCl
.29 (m, 5H), 7.18 (d, J ¼ 8.0 Hz, 2H), 5.65 (m, 1H), 5.58 (s, 2H), MHz, CDCl
.05 (dd, J ¼ 10.0 Hz, 1.2 Hz, 1H), 4.92 (dd, J ¼ 16.8 Hz, 1.2 Hz, 128.1, 127.7, 127.4, 127.0, 118.5, 52.0, 25.5, 22.3, 18.1. HRMS
3
): d 7.47–7.42 (m, 2H), 7.38– 1.65 (d, J ¼ 1.6 Hz, 3H), 1.62 (d, J ¼ 0.8 Hz, 3H). C NMR (100
3
): d 145.1, 135.2, 135.1, 132.6, 131.6, 128.9, 128.6,
1
3
+
H), 3.27 (m, 2H). C NMR (100 MHz, CDCl ): d 144.1, 135.0, (ESI) m/z calculated for C H N [M + H] 304.1808, found
3
20 22 3
34.1, 132.6, 132.4, 132.2, 130.4, 130.1, 129.8, 129.1, 128.4, 304.1811. IR (KBr lm): n 3025, 1654, 1602, 1494, 1249, 968, 728,
ꢁ
1
27.2, 126.9, 117.9, 52.3, 27.5. HRMS (EI) m/z calculated for 708 cm
.
+
C
3
18
H
16ClN
064, 3032, 1639, 1497, 920, 760, 736, 694 cm
-Allyl-1-benzyl-4-(4-methoxyphenyl)-1H-1,2,3-triazole (3o). 100–102 C. H NMR (400 MHz, CDCl
TLC: R
0.37 (3 : 1 hexane/EtOAc). Pale yellow liquid (70.0 mg, 2H), 7.43 (t, J ¼ 7.2 Hz, 2H), 7.38–7.26 (m, 6H), 7.25–7.18 (m,
3
[M] 309.1031, found 309.1033. IR (KBr lm): n
1-Benzyl-5-cinnamyl-4-phenyl-1H-1,2,3-triazole (3t). TLC: R
f
ꢁ
1
.
0.51 (2 : 1 hexane/EtOAc). White solid (74.5 mg, 53%). Mp ¼
ꢀ
1
5
3
): d 7.72 (d, J ¼ 7.2 Hz,
f
1
5
7
5
4
7%). H NMR (400 MHz, CDCl ): d 7.61 (d, J ¼ 8.8 Hz, 2H), 5H), 6.21 (d, J ¼ 16.0 Hz, 1H), 6.12 (dt, J ¼ 16.0, 5.2 Hz, 1H), 5.58
3
13
.36–7.30 (m, 3H), 7.20–7.18 (m, 2H), 6.96 (d, J ¼ 8.8 Hz, 2H), (s, 2H), 3.61 (dd, J ¼ 5.2, 1.2 Hz, 2H). C NMR (100 MHz,
.82 (m, 1H), 5.52 (s, 2H), 5.13 (dd, J ¼ 12.0 Hz, 1.6 Hz, 1H), CDCl ): d 145.9, 136.3, 135.0, 132.5, 131.3, 130.5, 129.0, 128.7,
3
1
3
.91 (dd, J ¼ 17.2 Hz, 1.6 Hz, 1H), 3.83 (s, 3H), 3.42 (m, 2H).
C
128.6, 128.3, 129.9, 127.8, 127.3, 127.2, 126.2, 123.6, 52.2, 26.3.
+
NMR (100 MHz, CDCl
3 21 3
): d 159.6, 145.9, 135.3, 132.5, 129.8, HRMS (ESI) m/z calculated for C24H N [M + H] 352.1808,
1
29.1, 128.6, 128.4, 127.3, 124.1, 117.8, 114.3, 55.5, 52.2, 27.2. found 352.1812. IR (KBr lm): n 3082, 3025, 1955, 1654,
+
ꢁ1
HRMS (ESI) m/z calculated for C19
H
20
N
3
O [M + H] 306.1601, 727 cm
.
found 306.1604. IR (KBr lm): n 2932, 1616, 1508, 1251, 1015,
5-Allyl-1-benzyl-4-hexyl-1H-1,2,3-triazole (3u). TLC: R
f
0.54
(2 : 1 hexane/EtOAc). Colorless oil (87.2 mg, 77%). H NMR (400
-Allyl-1-benzyl-4-(6-methoxynaphthalen-2-yl)-1H-1,2,3-tri- MHz, CDCl ): d 7.36–7.27 (m, 3H), 7.12 (dd, J ¼ 8.0 Hz, 2.0 Hz,
ꢁ
1
1
8
36, 727, 696 cm .
5
3
azole (3p). TLC: R 0.37 (2 : 1 hexane/EtOAc). Light yellow solid 2H), 5.72–5.58 (m, 1H), 5.46 (s, 2H), 5.07 (dq, J ¼ 10.4 Hz, 1.6 Hz,
f
ꢀ
1
(
106 mg, 75%). Mp ¼ 113–115 C. H NMR (400 MHz, CDCl
3
): 1H), 4.89 (dq, J ¼ 16.8 Hz, 1.6 Hz, 1H), 3.22 (dt, J ¼ 5.6 Hz,
d 8.04 (d, J ¼ 0.8 Hz, 1H), 7.83 (dd, J ¼ 8.4 Hz, 1.6 Hz, 1H), 7.79 (d, 1.6 Hz, 2H), 2.60 (t, J ¼ 7.6 Hz, 2H), 1.66 (quintet, J ¼ 6.4 Hz,
1
3
J ¼ 8.4 Hz, 1H), 7.76 (d, J ¼ 7.6 Hz, 1H), 7.38–7.31 (m, 3H), 7.23– 2H), 1.41–1.22 (m, 6H), 0.87 (t, J ¼ 6.8 Hz, 3H). C NMR (100
7
.21 (m, 2H), 7.17–7.14 (m, 2H), 5.87 (m, 1H), 5.57 (s, 2H), 5.18 MHz, DMSO-d ): d 144.8, 136.1, 133.3, 130.4, 128.6, 127.8, 127.2,
6
(
3
1
dd, J ¼ 10.4 Hz, 1.2 Hz, 1H), 4.98 (dd, J ¼ 17.2 Hz, 1.2 Hz, 1H), 116.7, 50.6, 30.9, 28.9, 28.2, 25.9, 24.2, 22.0, 13.8. HRMS (ESI) m/
1
3
+
.93 (s, 3H), 3.52 (m, 2H). C NMR (100 MHz, CDCl ): d 158.1, z calculated for C H N [M + H] 284.2121, found 284.2127. IR
3 18 25 3
ꢁ1
46.2, 135.2, 134.2, 132.5, 130.4, 129.9, 129.2, 129.1, 128.5, 127.4 (KBr lm): n 3065, 3033, 2928, 1640, 1456, 992, 729 cm
.
(2C), 126.8, 126.1, 126.0, 119.3, 118.0, 105.8, 55.5, 52.2, 27.3.
5-Allyl-1-(but-3-en-1-yl)-4-phenyl-1H-1,2,3-triazole (3v). TLC:
HRMS (EI) m/z calculated for C23
H
21
N
3
O 355.1687, found
R
f
0.55 (2 : 1 hexane/EtOAc). Pale yellow liquid (76.8 mg, 80%).
1
3
55.1685. IR (KBr lm): n 2936, 2840, 1634, 1600, 1263, 1029, 726,
H NMR (400 MHz, CDCl
6.8 Hz, 2H), 7.33 (tt, J ¼ 6.8 Hz, 1.2 Hz, 1H), 5.97 (m, 1H), 5.78
-Benzyl-5-(2-methylallyl)-4-phenyl-1H-1,2,3-triazole (3q). TLC: (m, 1H), 5.21 (dq, J ¼ 10.0 Hz, 0.8 Hz, 1H), 5.14–5.08 (m, 2H),
0.73 (2 : 1 hexane/EtOAc). Light yellow solid (104 mg, 90%). Mp 4.94 (dq, J ¼ 17.2 Hz, 0.8 Hz, 1H), 4.29 (t, J ¼ 7.2 Hz, 2H), 3.58
3
): d 7.67 (d, J ¼ 6.8 Hz, 2H), 7.42 (t, J ¼
ꢁ
1
695 cm
.
1
R
f
ꢀ
1
13
¼
56–58 C. H NMR (400 MHz, CDCl ): d 7.67 (d, J ¼ 7.2 Hz, 2H), (m, 2H), 2.70 (q, J ¼ 7.2 Hz, 2H). C NMR (100 MHz, CDCl ):
3
3
7
2
1
1
1
+
1
.42 (t, J ¼ 7.2 Hz, 2H), 7.39–7.28 (m, 4H), 7.19 (dd, J ¼ 7.6, 1.6 Hz, d 145.3, 133.5, 132.8, 131.6, 130.1, 128.8, 127.9, 127.3, 118.2,
H), 5.51 (s, 2H), 4.90 (t, J ¼ 1.2 Hz, 1H), 4.44 (s, 1H), 3.32 (s, 2H), 117.9, 47.5, 34.4, 27.2. HRMS (ESI) m/z calculated for C H N
1
5
18 3
1
3
+
.77 (d, J ¼ 0.4 Hz, 3H). C NMR (100 MHz, CDCl
3
): d 146.1, [M + H] 240.1495, found 240.1502. IR (KBr lm): n 3080, 1640,
ꢁ
1
40.3, 135.0, 131.4, 130.6, 128.9, 128.7, 128.3, 127.8, 127.2, 127.1, 1495, 918, 766, 699 cm
12.8, 52.0, 30.9, 22.9. HRMS (ESI) m/z calculated for C19
.
H N
20 3
[M
5-Allyl-1-(pent-4-en-1-yl)-4-phenyl-1H-1,2,3-triazole (3w). TLC:
+
1
H] 290.1652, found 290.1654. IR (KBr lm): n 3063, 3031, 1605,
R
f
0.70 (2 : 1 hexane/EtOAc). Pale yellow liquid (77.7 mg, 77%). H
ꢁ
1
496, 1251, 890, 770, 729 cm
.
NMR (400 MHz, CDCl
3
): d 7.67 (d, J ¼ 7.2 Hz, 2H), 7.41 (t, J ¼
1
-Benzyl-4-phenyl-5-(2-phenylallyl)-1H-1,2,3-triazole (3r). TLC: 7.2 Hz, 2H), 7.33 (t, J ¼ 7.2 Hz, 1H), 5.95 (m, 1H), 5.79 (m, 1H),
1
R 0.54 (2 : 1 hexane/EtOAc). Colorless liquid (120 mg, 86%). H 5.20 (d, J ¼ 10.0 Hz, 1H), 5.07 (d, J ¼ 10.0 Hz, 1H), 5.03 (d, J ¼
f
NMR (400 MHz, CDCl ): d 7.69 (dt, J ¼ 7.2, 1.6 Hz, 2H), 7.41 (t, J ¼ 17.2 Hz, 1H), 4.95 (d, J ¼ 17.2 Hz, 1H), 4.23 (t, J ¼ 7.2 Hz, 2H), 3.57
3
1
3
7
5
2
1
1
.2 Hz, 2H), 7.37–7.28 (m, 9H), 7.22–7.13 (m, 2H), 5.52 (s, 2H), (m, 2H), 2.14 (q, J ¼ 7.2 Hz, 2H), 2.04 (quin, J ¼ 7.2 Hz, 2H).
C
.47 (t, J ¼ 1.6 Hz, 1H), 4.65 (t, J ¼ 2.0 Hz, 1H), 3.82 (t, J ¼ 2.0 Hz, NMR (100 MHz, CDCl
3
): d 145.3, 136.8, 132.8, 131.6, 130.0, 128.7,
1
3
H). C NMR (100 MHz, CDCl
31.2, 130.3, 129.0, 128.8, 128.6, 128.4, 128.3, 128.0, 127.4, 127.1, calculated for C16
25.7, 114.3, 52.2, 28.5. HRMS (ESI) m/z calculated for C24 (KBr lm): n 3079, 2979, 1640, 1495, 916, 765, 700 cm .
3
): d 146.4, 142.6, 139.7, 134.9, 127.8, 127.2, 117.8, 116.1, 47.4, 30.7, 29.1, 27.1. HRMS (ESI) m/z
+
20 3
H N [M + H] 254.1652, found 254.1660. IR
ꢁ
1
H N
22 3
2764 | RSC Adv., 2018, 8, 2759–2767
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-Allyl-1-(hex-5-en-1-yl)-4-phenyl-1H-1,2,3-triazole (3x). TLC:
RSC Advances
5
Synthesis of 3-phenyl-4,7,8,9-tetrahydro-[1,2,3]triazolo[1,5-a]
f
R 0.65 (2 : 1 hexane/EtOAc). Pale yellow liquid (69.5 mg, 65%). azocine (6w). The diene 3w (50.7 mg, 200 mmol) was dissolved in
1
st
H NMR (400 MHz, CDCl
3
): d 7.68–7.65 (m, 2H), 7.43–7.39 (m, anhydrous CH
2
Cl
2
(6 mL). A solution of Grubbs' 1 generation
Cl (3.3 mL) was
2
1
0
7
2
1
2
H), 7.34–7.31 (m, 1H), 5.95 (m, 1H), 5.76 (m, 1H), 5.20 (dd, J ¼ catalyst (8.2 mg, 10.0 mmol) in anhydrous CH
2
2
0.0 Hz, 0.8 Hz, 1H), 5.04–4.98 (m, 2H), 4.94 (dd, J ¼ 8.8 Hz, added to the reaction mixture via a cannula. The reaction
.8 Hz, 1H), 4.23 (t, J ¼ 7.6 Hz, 2H), 3.57 (m, 2H), 2.10 (q, J ¼ mixture was stirred at room temperature for overnight, and was
.6 Hz, 2H), 1.94 (quin, J ¼ 7.6 Hz, 2H), 1.47 (quin, J ¼ 7.6 Hz, brought to reux for 6 h. Upon completion of the reaction, the
1
3
H). C NMR (100 MHz, CDCl ): d 145.3, 138.0, 132.8, 131.6, solvent was removed in vacuo. The residue was puried by
3
29.9, 128.8, 127.8, 127.3, 117.8, 115.3, 48.0, 33.2, 29.5, 27.1, column chromatography to afford 6w as pale yellow liquid
+
1
5.9. HRMS (ESI) m/z calculated for C17
H
22
N
3
[M + H] 268.1808, (39.0 mg, 87%). TLC: R
): d 7.61 (d, J ¼ 7.6 Hz, 2H), 7.44 (t, J ¼ 7.6 Hz, 2H),
7.35 (t, J ¼ 7.6 Hz, 1H), 5.79–5.67 (m, 2H), 4.53 (t, J ¼ 5.2 Hz, 2H),
f
0.35 (2 : 1 hexane/EtOAc). H NMR (400
found 268.1814. IR (KBr lm): n 3079, 2978, 1640, 1495, 914, MHz, CDCl
3
ꢁ
1
7
69, 698 cm
-Allyl-4-phenyl-1-(2-vinylphenyl)-1H-1,2,3-triazole (3y). TLC: 3.64 (d, J ¼ 4.8 Hz, 2H), 1.90–1.82 (m, 4H). C NMR (100 MHz,
R 0.6 (2 : 1 hexane/EtOAc). Light yellow solid (60.8 mg, 53%). CDCl ): d 144.4, 132.9, 131.7, 128.8, 128.4, 127.9, 127.8, 127.1,
.
1
3
5
f
3
ꢀ
1
Mp ¼ 81–83 C. H NMR (400 MHz, CDCl ): d 7.83 (d, J ¼ 7.6 Hz, 47.2, 27.2, 24.4, 23.1. HRMS (ESI) m/z calculated for C H N
3
14 16 3
+
2
7
1
1
¼
H), 7.74 (d, J ¼ 8.0 Hz, 1H), 7.54 (t, J ¼ 7.6 Hz, 1H), 7.47 (t, J ¼ [M + H] 226.1339, found 226.1336. IR (KBr lm): n 2929, 1665,
ꢁ
1
.6 Hz, 2H), 7.44–7.36 (m, 2H), 7.31 (d, J ¼ 7.6 Hz, 1H), 6.18 (dd, 1626, 1447, 733, 698 cm
.
7.6 Hz, 11.2 Hz, 1H), 5.73 (d, J ¼ 17.6 Hz, 1H), 5.72–5.65 (m,
Synthesis of (Z)-3-phenyl-7,8,9,10-tetrahydro-4H-[1,2,3]tri-
H), 5.27 (d, J ¼ 10.8 Hz, 1H), 5.02 (d, J ¼ 10.0 Hz, 1H), 4.81 (d, J azolo[1,5-a]azonine (6x) and (E)-1,10-bis(5-allyl-4-phenyl-1H-
1
3
0
16.4 Hz, 1H), 3.43 (d, J ¼ 5.2 Hz, 2H). C NMR (100 MHz, 1,2,3-triazol-1-yl)dec-5-ene (6x ). The diene 3x (53.5 mg, 200
): d 144.9, 135.5, 133.7, 132.8, 132.3, 131.3, 130.9, 130.7, mmol) was dissolved in anhydrous CH Cl (6 mL). A solution of
28.9, 128.5, 128.1, 127.2 (2C), 126.4, 118.2, 117.9, 27.5. HRMS Grubbs' 1 generation catalyst (8.2 mg, 10.0 mmol) in anhydrous
CDCl
3
2
2
st
1
+
(ESI) m/z calculated for C H N [M + H] 288.1495, found CH Cl (3.3 mL) was added to the reaction mixture via
19 18 3 2 2
2
6
88.1492. IR (KBr lm): n 3063, 2964, 1640, 1494, 991, 769, a cannula. The reaction mixture was brought to reux for 8 h.
ꢁ1
98 cm
.
Upon completion of the reaction, the solvent was removed in
5
-Allyl-4-phenyl-1-(2-vinylbenzyl)-1H-1,2,3-triazole (3z). TLC: vacuo. The residue was puried by column chromatography to
0
R
f
0.35 (6 : 1 hexane/EtOAc). Light brown liquid (66.6 mg, 55%). afford 6x as a white solid (31.0 mg, 65%) and a dimer 6x as
1
H NMR (400 MHz, CDCl
3
): d 7.70 (d, J ¼ 6.8 Hz, 2H), 7.50 (d, J ¼ colorless liquid (8.0 mg, 8%). 6x: TLC: R
f
0.2 (2 : 1 hexane/
): d 7.68
ꢀ
1
8
.0 Hz, 1H), 7.43 (t, J ¼ 7.6 Hz, 2H), 7.35 (t, J ¼ 7.6 Hz, 1H), 7.30 EtOAc). Mp ¼ 201–203 C. H NMR (400 MHz, CDCl
3
(
t, J ¼ 7.6 Hz, 1H), 7.20 (t, J ¼ 7.6 Hz, 1H), 7.03 (dd, J ¼ 16.8 Hz, (d, J ¼ 7.6 Hz, 2H), 7.45 (t, J ¼ 7.6 Hz, 2H), 7.36 (t, J ¼ 7.6 Hz,
1
1
1
2
1
1
C
0.8 Hz, 1H), 6.81 (d, J ¼ 7.6 Hz, 1H), 5.80 (m, 1H), 5.67 (dd, J ¼ 1H), 5.81 (m, 1H), 5.66 (m, 1H), 4.51 (t, J ¼ 6.0 Hz, 2H), 3.61 (d, J
7.2 Hz, 0.8 Hz, 1H), 5.63 (s, 2H), 5.42 (dd, J ¼ 12.0 Hz, 0.8 Hz, ¼ 7.6 Hz, 2H), 2.35–2.30 (m, 2H), 2.01 (quin, J ¼ 6.4 Hz, 2H),
1
3
H), 5.13 (d, J ¼ 10.4 Hz, 1H), 4.88 (d, J ¼ 17.2 Hz, 1H), 3.41 (m, 1.67–1.61 (m, 2H). C NMR (100 MHz, CDCl
3
): d 145.2, 131.7,
1
3
3
H). C NMR (100 MHz, CDCl ): d 146.0, 136.7, 133.4, 132.3, 131.5, 131.0, 128.9, 128.0, 127.6, 126.3, 45.8, 25.9, 25.1, 23.0,
+
18 3
32.1, 131.4, 130.7, 128.9, 128.6, 128.4, 128.0, 127.5, 127.3, 21.9. HRMS (ESI) m/z calculated for C15H N [M + H] 240.1495,
26.8, 118.2, 117.8, 49.8, 27.1. HRMS (ESI) m/z calculated for found 240.1498. IR (KBr lm): n 2959, 2932, 1491, 733, 720,
+
ꢁ1
20
20 3
H N [M + H] 302.1652, found 302.1646. IR (KBr lm): n 697 cm .
ꢁ1
0
1
3062, 3033, 1639, 1608, 1495, 919, 771, 699 cm
.
6x : TLC: R 0.17 (2 : 1 hexane/EtOAc). H NMR (400 MHz,
f
CDCl ): d 7.67 (d, J ¼ 7.2 Hz, 4H), 7.42 (t, J ¼ 7.2 Hz, 4H), 7.34 (t, J
3
¼
7.2 Hz, 2H), 6.00–5.91 (m, 2H), 5.39–5.35 (m, 2H), 5.21 (d, J ¼
Experimental procedure for ring closing metathesis
Synthesis of 3-phenyl-7,8-dihydro-4H-[1,2,3]triazolo[1,5-a] 3.57 (m, 4H), 2.09–2.01 (m, 4H), 1.96–1.89 (m, 4H), 1.43 (quin, J
1
0.4 Hz, 2H), 4.95 (d, J ¼ 17.2 Hz, 2H), 4.25–4.22 (m, 4H), 3.59–
1
3
azepine (6v). The diene 3v (47.9 mg, 200 mmol) was dissolved in ¼ 7.6 Hz, 4H). C NMR (100 MHz, CDCl ): d 145.2, 132.8, 131.4,
3
st
anhydrous CH
2
Cl
2
(6 mL). A solution of Grubbs' 1 generation 130.3, 130.1, 128.9, 128.0, 127.4, 117.9, 48.2, 32.0, 29.6, 27.2,
+
catalyst (8.2 mg, 10.0 mmol) in anhydrous CH
2 2
33 39 6
Cl (3.3 mL) was 26.6. HRMS (ESI) m/z calculated for C H N [M + H] 507.3231,
added to the reaction mixture via a cannula, and stirred at room found 507.3232. IR (KBr lm): n 2925, 1660, 1600, 1495, 917,
ꢁ
1
temperature for 19 h. Upon completion of the reaction, the 770, 698 cm
solvent was removed in vacuo. The residue was puried by
Synthesis of 3-phenyl-4H-benzo[f][1,2,3]triazolo[1,5-a]aze-
column chromatography to afford 6v as a pale green liquid pine (6y). The diene 3y (52.0 mg, 180 mmol) was dissolved in
.
1
st
(33.3 mg, 79%). TLC: R
f
2 2
0.3 (2 : 1 hexane/EtOAc). H NMR (400 anhydrous CH Cl (6 mL). A solution of Grubbs' 1 generation
MHz, CDCl
3
): d 7.60 (d, J ¼ 7.2 Hz, 2H), 7.44 (t, J ¼ 7.2 Hz, 2H), catalyst (8.2 mg, 10.0 mmol) in anhydrous CH Cl (3.3 mL) was
2
2
7
3
.35 (t, J ¼ 7.2 Hz, 1H), 5.75–5.73 (m, 2H), 4.71 (t, J ¼ 6.0 Hz, 2H), added to the reaction mixture via a cannula. The reaction
13
.70–3.69 (m, 2H), 2.55–2.52 (m, 2H). C NMR (100 MHz, mixture was stirred at room temperature for 8 h. Upon
CDCl ): d 144.7, 133.2, 131.5, 129.0, 128.8, 127.9, 127.8, 123.2, completion of the reaction, the solvent was removed in vacuo.
3
4
7.9, 27.9, 25.5. HRMS (ESI) m/z calculated for C H N [M + The residue was puried by column chromatography to afford
13 14 3
+
H] 212.1182, found 212.1185. IR (KBr lm): n 3058, 1660, 1624, 6y as a white solid (43.0 mg, 92%). TLC: R 0.37 (6 : 1 hexane/
1
f
ꢁ1
498, 772, 699 cm .
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ꢀ
1
EtOAc). Mp ¼ 96–98 C. H NMR (400 MHz, CDCl
7.6 Hz, 1.2 Hz, 1H), 7.71 (d, J ¼ 7.6 Hz, 2H), 7.50–7.41 (m, 4H),
.41–7.36 (m, 2H), 6.65 (d, J ¼ 10.4 Hz, 1H), 6.18 (m, 1H), 3.51 (d,
3
): d 8.15 (dd, J
(c) R. J. Pieters, D. T. S. Rijkers and R. M. J. Liskamp, QSAR
Comb. Sci., 2007, 26, 1181; (d) A. J. Dirks, J. Cornelissen,
F. L. van Del, J. C. M. van Hest, R. J. M. Nolte,
A. E. Rowan and F. Rutjes, QSAR Comb. Sci., 2007, 26, 1200;
(e) J. M. Baskin and C. R. Bertozzi, QSAR Comb. Sci., 2007,
26, 1211; (f) C. M. Salisbury and B. F. Cravatt, QSAR Comb.
Sci., 2007, 26, 1229.
5 (a) H. Nandivada, X. W. Jiang and J. Lahann, Adv. Mater.,
2007, 19, 2197; (b) D. Fournier, R. Hoogenboom and
U. S. Schubert, Chem. Soc. Rev., 2007, 36, 1369; (c)
P. L. Golas and K. Matyjaszewski, QSAR Comb. Sci., 2007,
26, 1116; (d) W. H. Binder and C. Kluger, Curr. Org. Chem.,
2006, 10, 1791.
¼
7
1
3
J ¼ 6.4 Hz, 2H). C NMR (100 MHz, CDCl ): d 142.2, 135.0,
3
1
1
C
34.9, 130.9, 130.8, 130.2, 129.0, 128.8, 128.7, 128.2, 128.1,
27.9, 127.6, 124.0, 21.2. HRMS (ESI) m/z calculated for
+
17
H
14
N
3
[M + H] 260.1182, found 260.1179. IR (KBr lm): n
ꢁ
1
2
919, 1700, 1600, 1491, 992, 772, 699 cm
Synthesis of (Z)-3-phenyl-4,11-dihydrobenzo[f][1,2,3]triazolo
1,5-a]azocine (6z). The diene 3z (47.0 mg, 150 mmol) was dis-
solved in anhydrous CH Cl (6 mL). A solution of Hoveyda-
Grubbs' 2 generation catalyst (5.0 mg, 7.9 mmol) in anhydrous
CH Cl (3.3 mL) was added to the reaction mixture via
.
[
2
2
nd
2
2
a cannula. The reaction mixture was stirred at room tempera-
ture for 4 h. Upon completion of the reaction, the solvent was
removed in vacuo. The residue was puried by column chro-
matography to afford 6z as a pale green solid (29.5 mg, 72%).
6 (a) J. F. Lutz and H. Schlaad, Polymer, 2008, 49, 817; (b) P. Wu
and V. V. Fokin, Aldrichimica Acta, 2007, 40, 7; (c)
K. A. Kalesh, P. Y. Yang, R. Srinivasan and S. Q. Yao, QSAR
Comb. Sci., 2007, 26, 1135; (d) F. Santoyo-Gonz lez and
F. Hernandez-Mateo, Top. Heterocycl. Chem., 2007, 7, 133;
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I. Aprahamian, R. D. Rohde, H. D. Agnew, J. R. Heath and
J. F. Stoddart, QSAR Comb. Sci., 2007, 26, 1165; (b)
I. Aprahamian, O. S. Miljanic, W. R. Dichtel, K. Isoda,
T. Yasuda, T. Kato and J. F. Stoddart, Bull. Chem. Soc. Jpn.,
2007, 80, 1856; (c) A. B. Braunschweig, W. R. Dichtel,
O. S. Miljanic, M. A. Olson, J. M. Spruell, S. I. Khan,
J. R. Heath and J. F. Stoddart, Chem.–Asian J., 2007, 2, 634;
for selected papers see: (d) W. B. Zhang, Y. Tu, R. Ranjan,
R. M. VanHorn, S. Leng, J. Wang, M. J. Polce,
C. Wesdemiotis, R. P. Quirk, G. R. Newkome and
S. Z. D. Cheng, Macromolecules, 2008, 41, 515; (e)
J. S. Marois, K. Cantin, A. Desmarais and J. F. Morin, Org.
Lett., 2008, 10, 33; (f) V. Aucagne, K. D. Haenni,
D. A. Leigh, P. J. Lusby and D. B. Walker, J. Am. Chem. Soc.,
ꢀ
1
TLC: R 0.27 (6 : 1 hexane/EtOAc). Mp ¼ 159–161 C. H NMR
f
(
400 MHz, CDCl ): d 7.58–7.54 (m, 3H), 7.45–7.38 (m, 3H), 7.37–
3
7
6
2
1
1
.35 (m, 2H), 7.30 (d, J ¼ 8.4 Hz, 1H), 7.08 (d, J ¼ 10.4 Hz, 1H),
.03 (dt, J ¼ 10.4 Hz, 7.6 Hz, 1H), 5.49 (s, 2H), 3.30 (d, J ¼ 8.0 Hz,
1
3
3
H). C NMR (100 MHz, CDCl ): d 144.8, 139.2, 134.0, 131.5,
31.3, 130.9, 129.3, 128.8, 128.7, 128.6, 128.2, 128.0, 127.7,
26.2, 53.4, 22.6. HRMS (ESI) m/z calculated for C18 [M +
16 3
H N
+
H] 274.1339, found 274.1336. IR (KBr lm): n 3025, 2360, 1494,
9
ꢁ
1
95, 754, 735, 699 cm .
Conflicts of interest
There are no conicts to declare.
Acknowledgements
This research was supported by the Basic Science Research
Program through the National Research Foundation of Korea
(NRF) funded by the Ministry of Science, ICT and Future Plan-
ning (NRF-2015R1A2A2A01004511).
Notes and references
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