Alkenes as azido precursors for the one-pot synthesis of 1,2,3-triazoles catalyzed by copper nanoparticles on activated carbon

Article abstract of DOI:10.1021/jo400110m

A one-pot protocol for the synthesis of 1,2,3-triazoles has been developed starting from inactivated alkenes and based on two click reactions: the azidosulfenylation of the carbon-carbon double bond and the copper-catalyzed azide-alkyne cycloaddition (CuAAC). High yields of the β-methylsulfanyl triazoles have been attained using CuNPs/C as catalyst, with other commercial copper catalysts being completely inactive. The versatility of the methylsulfanyl group has been demonstrated through a series of synthetic transformations, including direct access to 1-vinyl and 4-monosubstituted triazoles.

Full text of DOI:10.1021/jo400110m

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Note
Alkenes as Azido Precursors for the One-Pot Synthesis of 1,2,3-
Triazoles Catalyzed by Copper Nanoparticles on Activated Carbon
Francisco Alonso, Yanina Moglie, Gabriel Radivoy, and Miguel Yus
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/jo400110m • Publication Date (Web): 25 Apr 2013
Downloaded from http://pubs.acs.org on April 30, 2013
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Alkenes as Azido Precursors for the One-Pot Synthesis of 1,2,3-Triazoles
Catalyzed by Copper Nanoparticles on Activated Carbon
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Francisco Alonso,†,* Yanina Moglie,† Gabriel Radivoy,‡ and Miguel Yus†
†
Departamento de Química Orgánica, Facultad de Ciencias and Instituto de Síntesis Orgánica (ISO)
Universidad de Alicante, Apdo. 99, 03080 Alicante (Spain)
‡
Departamento de Química, Instituto de Química del Sur (INQUISURꢀCONICET), Universidad
Nacional del Sur, Avenida Alem 1253, 8000 Bahía Blanca (Argentina)
Eꢀmail: falonso@ua.es
Abstract: A oneꢀpot protocol for the synthesis of 1,2,3ꢀtriazoles has been developed starting from
inactivated alkenes and based on two click reactions: the azidosulfenylation of the carbonꢀcarbon
double bond and the copperꢀcatalyzed azideꢀalkyne cycloaddition (CuAAC). High yields of the βꢀ
methylsulfanyl triazoles have been attained using CuNPs/C as catalyst, with other commercial copper
catalysts being completely inactive. The versatility of the methylsulfanyl group has been demonstrated
through a series of synthetic transformations, including the direct access to 1ꢀvinyl and 4ꢀ
monosubstituted triazoles.
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Click chemistry has become one of the most important concepts in modern chemistry.1 It represents
certain highly efficient and reliable reactions which are modular, wide in scope, high yielding,
stereospecific, and proceed under simple and benign conditions with straightforward procedures for
product isolation. Recently, the click’s chemistry first decade has been celebrated,2 with an endless list
of disciplines having been benefited along this time from the unique advantages offered by this type of
reactions. The copperꢀcatalyzed azideꢀalkyne cycloaddition (CuAAC)3 fulfils the aforementioned series
of rigorous criteria, as defined by Sharpless et al., turning this reaction into the click reaction by
antonomasia.4 The nucleophilic opening of springꢀloaded rings (i.e., epoxides, aziridines, cyclic
sulfates, cyclic sulfamidates, aziridinium ions, and episulfonium ions) also belongs to the privileged list
of click reactions because they are reliable, stereospecific, often highly regioselective, and nearly
quantitative.1
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The CuAAC has been traditionally implemented with preꢀformed organic azides. More
advantageous are, however, the methodologies in which the organic azides are generated in situ from
organic halides5 (threeꢀcomponent azideꢀalkyne cycloaddition) because (a) hazards derived from their
isolation and handling are minimized, (b) the time consuming and waste generating additional synthetic
step are avoided, and (c) the common organic solvents utilized (e.g., dioxane, toluene, DMF,
dichloromethane, hexane) can be replaced by neat water. In this vain, efforts have been recently
devoted to develop new catalytic systems which allow the CuAAC from other different azide
precursors, namely: amines,6 tosylates,7 diarylidodonium salts,8 epoxides,9 alcohols,10 and boronic
acids.11 Favi et al. reported the oneꢀpot copper(II)ꢀcatalyzed azaꢀMichael addition of trimethylsilyl
azide to 1,2ꢀdiazaꢀ1,3ꢀdienes and copper(I)ꢀcatalyzed 1,3ꢀdipolar cycloaddition of the in situꢀgenerated
αꢀazidohydrazones with alkynes.12 However, alkenes are the most commonly available starting
materials which can provide a carbon framework. To the best of our knowledge, the synthesis of 1,2,3ꢀ
triazoles from inactivated alkenes has never been described.
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On the other hand, there is an upsurge of interest in the use of nanostructured copper catalysts for the
CuAAC because of their large surfaceꢀtoꢀvolume ratio, varied morphology, and sustainable catalytic
applications.13 Owing to our dedication to study and understand the reactivity of metal colloids,14 we
found out that active copper [obtained from CuCl2ꢁ2H2O, lithium metal, and a catalytic amount of 4,4'ꢀ
diꢀtertꢀbutylbiphenyl (DTBB) in THF at room temperature] was able to reduce different organic
functionalities under very mild conditions.15 We also discovered that copper nanoparticles (CuNPs) are
formed when the active copper is generated from anhydrous CuCl2 under the above mentioned
conditions. These unsupported copper nanoparticles (10 mol%) effectively catalysed the CuAAC in the
presence of triethylamine at 65 ºC in THF.16 Remarkably short reaction times (10–120 min),
comparable to those previously reported under microwave heating, were recorded in the absence of any
stabilising additive or ligand. Unfortunately, the CuNPs underwent dissolution under the reaction
conditions which precluded their reuse. More recently, we introduced a catalyst consisting of oxidized
copper nanoparticles on activated carbon (CuNPs/C), readily prepared under mild conditions, which
exhibited a high versatility in the multicomponent click synthesis of 1,2,3ꢀtriazoles in water.17 Not only
organic halides but diazonium salts, anilines, and epoxides were successfully used as azide precursors
in the CuAAC (Scheme 1). We want to present herein the first oneꢀpot transformation of inactivated
olefins into 1,2,3ꢀtriazoles by taking advantage of two consecutive click reactions: (a) the ring opening
of inꢀsitu generated episulfonium ions by the azide anion and (b) the reaction of the inꢀsitu generated
azides with alkynes catalyzed by CuNPs/C.
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SCHEME 1. Multicomponent Synthesis of 1,2,3-Triazoles from Different Azide Precursors
Catalyzed by CuNPs/C in Water.
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R2(H)
R1
R1
HO
R2
N
N
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N
N
O
(R2)H
N
N
76-99%
70-93%
R2Hal
Hal = Cl, Br, I
70-100 ºC
3-10 h
R2
70 ºC, 3-10 h
0.5 mol% CuNPs/C
R1C CH, NaN3, H2O
+
ArNH2, t-BuONO
Hal = Cl, Br, I
70 ºC 2-24 h
ArN NBF4
70 ºC, 2-8 h
R1
R1
Ar
N
Ar
N
N
N
N
N
64-95%
71-92%
We envisaged the potential transformation of alkenes into triazoles inspired by the azasulfenylation
of alkenes developed by Trost et al.18 In this methodology, an alkene was treated with
dimethyl(methylthio)sulfonium tetrafluoroborate (DMTSF)19 at 0 ºC to room temperature, followed by
the addition of a nitrogen nucleophile at room temperature and stirring for 1–4 days. After an
optimization of the reaction conditions (i.e, solvent, catalyst, temperature, and reaction time) we
discovered a more convenient variation of this method in which the alkene was directly mixed with
CuNPs/C, DMTSF, and NaN3 in MeCN to produce the corresponding methylsulfanyl azide in only 1 h
at room temperature; apparently, the CuNPs accelerate this process. The subsequent reaction with the
alkyne represents, to the best of our knowledge, the first example of triazole synthesis from an
inactivated alkene in one pot (Scheme 2).
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SCHEME 2. Optimized Conditions for the One-Pot Synthesis of Triazoles from Alkenes
Catalyzed by CuNPs/C.
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With this methodology in hand, a series of representative alkenes and different alkynes were
subjected to this oneꢀpot consecutive doubleꢀclick protocol (Table 1). We first studied the reaction of
cyclohexene with various electronically different alkynes (Table 1, entries 1–5). Good yields were
recorded for the electronically neutral alkynes phenylacetylene (2a) and pꢀtolylacetylene (2b) as well
as for the electronically rich and poor 4ꢀmethoxyphenylacetylene (2c) and 4ꢀ
(trifluoromethyl)phenylacetylene (2d), respectively (Table 1, entries 1–4). The aliphatic alkyne octꢀ1ꢀ
yne was found to be more reluctant to react and needed prolonged heating in order to reach a yield
similar to those of the aromatic alkynes (Table 1, entry 5). Interestingly, a high control was achieved in
the monoꢀazidosulfenylation of cyclooctaꢀ1,5ꢀdiene (1b). The subsequent reaction with
phenylacetylene (2a) gave rise to the product 3ba in excellent yield, which possesses a carbonꢀcarbon
double bond available for further functionalization (Table 1, entry 6). Very similar yield and reaction
time as those in entry 6 were noted when starting from the oxacyclic olefin 2,5ꢀdihydrofuran (1c)
(Table 1, entry 7). It is noteworthy that the cyclic olefins 1a–1c provided exclusively the trans
methylsulfanyl triazolꢀ1ꢀyl products. These results are in agreement with the reaction taking place
through an episulfonium ion intermediate, which undergoes transꢀdiaxial ring opening through an SN2
process. This is the same trend we observed in the synthesis of 1,2,3ꢀtriazoles from cycloalkene
oxides.17c
Table 1. One-Pot Click Synthesis of 1,2,3-Triazoles from Alkenes Catalyzed by CuNPs/C.a
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Entry
1
Alkene
Alkyne
t (h)
16
Product
SCH3
Yield (%)b
81
N
Ph
N
N
3aa
2a
1a
1a
SCH3
2
3
4
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16
79
85
83
N
N
9
2b
2c
2d
N
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3ab
SCH3
1a
1a
MeO
F3C
OMe
CF3
N
N
N
3ac
SCH3
N
N
N
3ad
SCH3
N
5
6
1a
24
14
77
91
2e
2a
N
N
3ae
SCH3
Ph
N
N
N
1b
3ba
SCH3
O
7
2a
14
89
75
O
N
N
1c
N
3ca
Ph
N
N
N
8
9
2a
2a
16
16
1d
1e
SCH3
3da
N
CH3S
N
N
57
19
Ph
3ea
Ph
N
N
N
SCH3
3ea'
SCH3
N
10
2a
24
37
42
Ph
N
N
3fa
1f
SCH3
N
Ph
N
N
3fa'
Ph
SCH3
Ph
11
12
2a
2e
12
12
89
77
Ph
N
N
N
Ph
N
1g
3ga
1g
SCH3
N
N
3ge
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a Reagents and conditions: 1 (0.5 mmol), NaN3 (0.6 mmol), DMTSF (0.6 mmol), CuNPs/C (0.5 mol%),
MeCN (2 mL), r.t., 1 h; 2 (0.5 mmol), 70 ºC, t (h). b Isolated yield.
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We next studied the behavior of acyclic olefins in the title reaction. The symmetrical internal alkene
(Z)ꢀoctꢀ4ꢀene (1d), when combined with phenylacetylene (2a), furnished 3da with a 4R*,5R* relative
configuration proposed in view of the aforementioned trend (Table 1, entry 8). The azidosulfenylation
of the terminal olefin octꢀ1ꢀene (1e) was found to be less regioselective when compared with the
azidolysis of octꢀ1ꢀene oxide.17c In this case, the CuAAC with phenylacetylene (2a) yielded a ca. 3:1
mixture of regioisomers, the major one derived from the attack of the azide ion to the less hindered
position of the intermediate episulfonium ion (Table 1, entry 9). The stabilization of the partially
developed positive charge on the internal carbon atom of the episulfonium ion in the transition state
could account for the formation of the minor regioisomer 3ea'. Fortunately, the two regioisomers could
be easily separated by column chromatography. Triazoles 3fa and 3fa', derived from the unsymmetric
cyclic olefin 1ꢀmethylcyclohexꢀ1ꢀene, were produced in a near 1:1 regioisomeric ratio and could be
also separated (Table 1, entry 10). Finally, when styrene was subjected to the standard procedure, either
with phenylacetylene (2a) or octꢀ1ꢀyne (2e), the expected triazoles 3ga and 3ge where obtained,
respectively, in good yields as single regioisomers (Table 1, entries 11 and 12). In both cases, attack of
the azide ion to the internal carbon atom of the intermediate episulfonium ion was preferred as it was
also previously observed in the domino azidolysisꢀCuAAC of styrene oxide and phenylacetylene.17c
These results can be explained by the partially developed positive charge during the nucleophilic azide
attack in the unsymmetrical ringꢀopening transition state, which is more stabilized at the benzylic
position of the episulfonium ion. Recently, 1,2,3ꢀtriazoles have been succesfully applied in organic
synthesis as ligands,20 with compounds in Table 3 representing a new family of potential N,Sꢀtriazolyl
ligands.
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Contrary to the good recycling behaviour observed for CuNPs/C in other multicomponent click
reactions,17 in the present case reutilization was inefficient, very probably due to catalyst poisoning by
sulfur. Nevertheless, this fact is not so important if we take into account the low copper loading
deployed in the experiments (0.5 mol%). On the other hand, it is our premise that any laboratoryꢀmade
catalyst should be more efficient than commercially available catalysts used for the same purpose;
otherwise, it is difficult to economically justify the time, materials and human resources employed
during its preparation. With this principle in mind, we undertook a comparative study on the reactivity
of CuNPs/C with some commercially available copper sources. The standard conditions were applied
to the reaction of cyclohexene (1a) with DMTSF, NaN3, and phenylacetylene (2a) leading to 3aa
(Table 2). We were delighted to check that none of the commercial catalysts was active in this
transformation, where even the initial azidosulfenylation step failed (Table 2, entries 1–5). In contrast,
the copperꢀnanoparticle supported catalyst produced the desired product in good isolated yield (Table
2, entry 6). These results are in agreement with the fact that CuNPs/C could also catalyze the first
synthetic step. This catalytic role was clearly demonstrated by carrying out two experiments: (a) the
reaction of cyclohexene with DMTSF and NaN3 in MeCN at rt (1–24 h) gave a complex mixture of
products, with the expected azide representing only 5–24%; (b) the same reaction in the presence of 0.5
mol% CuNPs/C provided that azide quantitatively in only 1 h (see the Supporting Information).
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TABLE 2. One-Pot Click Synthesis of 1,2,3-Triazoles from Alkenes Catalyzed by Different
Copper Catalysts.a
SCH3
i) catalyst, DMTSF
NaN3, MeCN, rt, 1 h
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7
8
9
N
ii)
PhC
CH (2a), 70 ºC
Ph
N
N
3aa
1a
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entry
catalyst (mol% Cu)
Cu (1)
yield (%)b
1
2
3
4
5
6
ꢀc
ꢀc
ꢀc
CuCl (1)
CuCl2 (1)
CuO (1)
ꢀc
ꢀc
Cu2O (1)
CuNPs/C (0.5)
81
a 1a (0.5 mmol), NaN3 (0.6 mmol), DMTSF (0.6 mmol), MeCN (2 mL). b Isolated yield. c Not detected.
Finally, we sought to capitalize on the presence of the methylsulfanyl group to structurally modify
the triazoles 3 (Scheme 3). A variety of conditions were tested in order to achieve maximum
selectivity, with the best results being shown in Scheme 3. Oxidation of the parent triazole 3ga with
hydrogen peroxide was mild and fast giving a ca. 1:1 diastereomeric mixture of sulfoxide 4ga.
Sulfoxide elimination under thermal conditions led to the vinyl triazole 5ga in an overall quantitative
conversion. We must point out that the synthesis of 1ꢀvinylꢀ1,2,3ꢀtriazoles has been scarcely studied,21
with this method representing an effectual approach. Oxidation of the parent triazole 3ga to the
corresponding sulfone 6ga was easily accomplished with mꢀCPBA. Treatment of 6ga with sodium
amalgam in methanol afforded the 4ꢀmonosubstituted triazole 7a together with methyl (E)ꢀβꢀstyryl
sulfone (8a). These experiments prove the versatility of the βꢀ(methylsulfanyl)ethylꢀsubstituted 1,2,3ꢀ
triazoles 3.
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SCHEME 3. Synthetic Transformations of Triazole 3ga.
4
5
6
7
8
9
Ph
SCH3
N
H2SO4, i-PrOH
H2O2, MeOH
rt, 1 h
N
m-CPBA
CH2Cl2
0 ºC, 2 h
N
Ph
3ga
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O
O
O
+
Ph
Ph
S
S
N
N
N
N
N
N
Ph
Ph
4ga
99%, d.r. ~1:1
6ga
87%
NaHg, MeOH
Na2HPO4
-10 ºC to rt
10 h
PhMe, 120 ºC
10 h
SO2Me
8a
99%
Ph
Ph
Ph
Ph
N
NH
N
N
N
N
5ga
90%
7a
99%
In conclusion, we have described the first oneꢀpot synthesis of 1,2,3ꢀtriazoles from inactivated
alkenes through a sequence including two click steps catalyzed by CuNPs/C: the azidosulfenylation of
the olefin and the reaction of the inꢀsitu generated organic azide with the terminal alkyne. The βꢀ
methylsulfanyl triazoles, potential interesting ligands, are obtained regioꢀ and diastereoselectively in
75–91% isolated yields. In addition, the nanostructured catalyst displayed much higher catalytic
activity than the commercial bulk copper catalysts which failed in the first step. Furthermore, simple
and quantitative oxidationꢀelimination procedures allow the transformation of the products into 1ꢀ
vinylꢀ4ꢀsubstituted or 4ꢀmonosubstituted 1,2,3ꢀtriazoles.
EXPERIMENTAL SECTION
General: Anhydrous copper(II) chloride (97%), lithium powder (MEDALCHEMY S. L.), DTBB (4,4'ꢀ
diꢀtertꢀbutylbiphenyl), activated charcoal (Norit CA1), and sodium azide were commercially available.
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All the starting materials and other reagents were commercially available of the best grade and were
used without further purification. THF was dried in a solvent purification system using an alumina
column. Melting points are uncorrected. Infrared analysis was performed with a FTꢀIR
spectrophotometer equipped with an ATR component; wavenumbers are given in cm–1. NMR spectra
were recorded at 300 or 400 MHz for 1H NMR and 75 and 101 MHz for 13C NMR; chemical shifts are
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given in (δ) parts per million and coupling constants (J) in Hertz. Mass spectra (EI) were obtained at 70
eV with a GCꢀMS apparatus; fragment ions in m/z with relative intensities (%) in parenthesis. HRMS
analyses were also carried out in the electron impact mode (EI) at 70 eV using a quadrupole analyzer.
The purity of volatile compounds and the chromatographic analyses (GLC) were determined with a gas
chromatograph equipped with a flame ionization detector and a 30 m capillary column (0.32 mm
diameter, 0.25 ꢀm film thickness), using nitrogen (2 mL/min) as carrier gas, Tinjector = 270 ºC, Tcolumn
=
60 ºC (3 min) and 60–270 ºC (15 ºC/min); retention times (tr) are given in min. Thin layer
chromatography was carried out on TLC plastic sheets with silica gel. Column chromatography was
performed using silica gel of 40–60 microns (hexaneꢀEtOAc as eluent).
Typical Procedure for the Preparation of CuNPs/C:17a,b Anhydrous copper(II) chloride (135 mg, 1
mmol) was added to a suspension of lithium (14 mg, 2 mmol) and 4,4'ꢀdiꢀtertꢀbutylbiphenyl (DTBB,
27 mg, 0.1 mmol) in THF (2 mL) at room temperature under an argon atmosphere. The reaction
mixture, which was initially dark blue, rapidly changed to black, indicating that the suspension of
copper nanoparticles was formed. This suspension was diluted with THF (18 mL) followed by the
addition of the activated carbon (1.28 g). The resulting mixture was stirred for 1 h at room temperature,
filtered, and the solid successively washed with water (20 mL), THF (20 mL), and dried under vacuum.
Typical Procedure for the CuNPs/C-Catalyzed Synthesis of 1,2,3-Triazoles from Alkenes: NaN3
(39 mg, 0.6 mmol), freshly prepared dimethyl(methylthio)sulfonium tetrafluoroborate (DMTSF,19 118
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mg, 0.6 mmol), and cyclohexene (1a, 51 ꢂL, 0.5 mmol) were added to a suspension of CuNPs/C (10
mg, 0.5 mol% Cu) in MeCN (2 mL) at room temperature under an argon atmosphere.22 After stirring
for 1 h, phenylacetylene (2a, 55 ꢂL, 0.5 mmol) was added. The reaction mixture was warmed to 70 ºC
and monitored by TLC until total or steady conversion of the starting materials. Water (20 mL) was
added to the resulting mixture followed by extraction with EtOAc (3 × 10 mL). The collected organic
phases were dried with MgSO4 and the solvent was removed in vacuo to give the corresponding
triazole 3aa, which was purified by column chromatography (hexaneꢀEtOAc, 8:2).
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1-[(1R*,2R*)-2-(Methylthio)cyclohexyl]-4-phenyl-1H-1,2,3-triazole (3aa): Pale yellow solid (110.6
mg, 81%); m.p. 128.0–130.1 ºC; tr 18.53 min; Rf 0.61 (hexaneꢀEtOAc, 7:3); IR (KBr) ν 3119, 3082,
2935, 2923, 2850, 1480, 1460, 1435, 1211, 1178, 1076, 1048, 974, 762, 697 cm–1; 1H NMR (400 MHz,
CDCl3) δ 7.88–7.84 (m, 2H), 7.81 (s, 1H), 7.46–7.35 (m, 2H), 7.34–7.29 (m, 1H), 4.24 (td, J = 11.2,
4.2 Hz, 1H), 3.00 (td, J = 11.2, 4.2 Hz, 1H), 2.36–2.09 (m, 3H), 1.99–1.86 (m, 2H), 1.71 (s, 3H), 1.56–
1.42 (m, 3H); 13C NMR (101 MHz, CDCl3) δ 147.0, 130.8, 128.7, 128.0, 125.7, 119.5, 65.8, 50.4, 33.9,
33.3, 25.9, 25.1, 13.8; GCꢀMS (EI) m/z (%) 273 (26) [M+], 230 (27), 196 (12), 162 (14), 129 (46), 128
(68), 117 (14), 116 (22), 102 (16), 89 (15), 81 (100), 79 (20), 61 (19); HRMS (EI) m/z calcd. for
C15H19N3S 273.1300, found 273.1293.
1-{(1R*,2R*)-[2-(Methylthio)cyclohexyl]}-4-(p-tolyl)-1H-1,2,3-triazole (3ab): White solid (113.4
mg, 79%); m.p. 135.9–138.1 ºC; tr 19.79 min; Rf 0.54 (hexaneꢀEtOAc, 7:3); IR (neat) ν 3103, 2942,
2920, 2856, 1498, 1445, 1422, 1214, 1049, 977, 816 cm–1; 1H NMR (400 MHz, CDCl3) δ 7.78 (s, 1H),
7.75 (d, J = 8.0 Hz, 2H), 7.23 (d, J = 8.0 Hz, 2H), 4.23 (td, J = 11.3, 4.4 Hz, 1H), 3.00 (td, J = 11.3, 4.0
Hz, 1H), 2.38 (s, 3H), 2.33–2.25 (m, 1H), 2.24–2.11 (m, 2H), 1.99–1.85 (m, 2H), 1.70 (s, 3H), 1.56–
1.39 (m, 3H); 13C NMR (101 MHz, CDCl3) δ 147.3, 137.9, 129.6, 128.1, 125.7, 119.3, 65.9, 50.5, 34.1,
33.4, 26.0, 25.3, 21.4, 14.0; GCꢀMS (EI) m/z (%) 287 (22) [M+], 244 (14), 131 (10), 130 (19), 129 (51),
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128 (15), 115 (18), 81 (100), 79 (15), 77 (10), 61 (19); HRMS (EI) m/z calcd. for C16H21N3S 287.1456,
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found 287.1461.
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4-(4-Methoxyphenyl)-1-{(1R*,2R*) [2-(methylthio)cyclohexyl]}-1H-1,2,3-triazole (3ac): Pale yellow
solid (128.8 mg, 85%); m.p. 132.8–135.5 ºC; tr 21.95 min; Rf 0.53 (hexaneꢀEtOAc, 6:4); IR (neat) ν
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3102, 2937, 2925, 2857, 1497, 1245, 1175, 1030, 828, 815 cm–1; H NMR (400 MHz, CDCl3) δ 7.78
(d, J = 8.8 Hz, 2H), 7.74 (s, 1H), 6.96 (d, J = 8.8 Hz, 2H), 4.23 (td, J = 11.3, 4.4 Hz, 1H), 3.84 (s, 3H),
3.00 (td, J = 11.3, 4.1 Hz, 1H), 2.33–2.06 (m, 3H), 1.98–1.84 (m, 2H), 1.72 (s, 3H), 1.55–1.41 (m, 3H);
13C NMR (101 MHz, CDCl3) δ 159.7, 147.0, 127.1, 123.6, 118.9, 114.3, 65.9, 55.5, 50.4, 34.1, 33.4,
26.0, 25.3, 13.9; GCꢀMS (EI) m/z (%) 303 (35) [M+], 260 (29), 146 (16), 132 (21), 129 (59), 121 (10),
89 (13), 81 (100), 79 (20), 61 (20); HRMS (EI) m/z calcd. for C16H21N3OS 303.1405, found 303.1411.
1-{(1R*,2R*)-[2-(Methylthio)cyclohexyl]}-4-[4-(trifluoromethyl)phenyl]-1H-1,2,3-triazole (3ad):
Pale yellow solid (141.6 mg, 83%); m.p. 118.4–120.6 ºC; tr 18.18 min; Rf 0.53 (hexaneꢀEtOAc, 7:3);
IR (neat) ν 3099, 2943, 2924, 2856, 1620, 1329, 1158, 1123, 1105, 1065, 978, 839 cm–1; 1H NMR (400
MHz, CDCl3) δ 7.98 (d, J = 8.5 Hz, 2H), 7.91 (s, 1H), 7.68 (d, J = 8.5 Hz, 2H), 4.23 (td, J = 11.5, 4.2
Hz, 1H), 3.01 (td, J = 11.5, 4.2 Hz, 1H), 2.36–2.11 (m, 3H), 2.01–1.87 (m, 2H), 1.74 (s, 3H), 1.58–1.43
(m, 3H); 13C NMR (101 MHz, CDCl3) δ 145.8, 134.3, 130.0 (q, J = 32.8 Hz, CF3), 125.9, 125.6, 120.5,
65.9, 50.4, 34.1, 33.4, 25.9, 25.2, 13.8; GCꢀMS (EI) m/z (%) 341 (4) [M+], 129 (20), 128 (100), 81 (95),
79 (20), 61 (22); HRMS (EI) m/z calcd. for C16H18F3N3S 341.1174, found 341.1180.
4-Hexyl-1-{(1R*,2R*)-[2-(methylthio)cyclohexyl]}-1H-1,2,3-triazole (3ae): Pale orange solid (108.3,
77%); m.p. 61.0–64.0 ºC; tr 17.12 min; Rf 0.62 (hexaneꢀEtOAc, 6:4); IR (neat) ν 3121, 3069, 2924,
2855, 1445, 1215, 1152, 1056, 847, 724 cm–1; 1H NMR (400 MHz, CDCl3) δ 7.33 (s, 1H), 4.16 (td, J =
11.3, 4.2 Hz, 1H), 2.94 (td, J = 11.3, 4.2 Hz, 1H), 2.73 (t, J = 7.7 Hz, 2H), 2.32–2.24 (m, 1H), 2.19–
2.05 (m, 2H), 1.96–1.84 (m, 2H), 1.74–1.63 (m, 2H), 1.66 (s, 3H), 1.52–1.25 (m, 9H), 0.88 (t, J = 6.4
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Hz, 3H); C NMR (101 MHz, CDCl3) δ 147.8, 120.7, 65.7, 50.5, 34.1, 33.4, 31.7, 29.6, 29.0, 26.0,
25.8, 25.3, 22.7, 14.2, 13.9; GCꢀMS (EI) m/z (%) 281 (2) [M+], 129 (21), 128 (82), 80 (14), 79 (18), 61
(22), 55 (10), 53 (10); HRMS (EI) m/z calcd. for C15H27N3S 281.1926, found 281.1936.
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1-[(1R*,8R*,Z)-8-(Methylthio)cyclooct-4-en-1-yl)]-4-phenyl-1H-1,2,3-triazole (3ba): White solid
(136.1 mg, 91%); m.p. 111.2–113.8 ºC; tr 21.25 min; Rf 0.60 (hexaneꢀEtOAc, 6:4); IR (neat) ν 3120,
2948, 2919, 1436, 1083, 1051, 764, 712, 704, 692 cm–1; 1H NMR (300 MHz, CDCl3) δ 7.92–7.86 (m,
2H), 7.83 (s, 1H), 7.47–7.39 (m, 2H), 7.38–7.33 (m, 1H), 5.83–5.67 (m, 2H), 4.86 (td, J = 9.7, 3.4 Hz,
1H), 3.46–3.36 (m, 1H), 2.79–2.22 (m, 4H), 2.19–1.98 (m, 4H), 1.77 (s, 3H); 13C NMR (101 MHz,
CDCl3) δ 146.8, 130.7, 130.5, 128.9, 128.2, 127.7, 125.9, 120.5, 65.0, 51.3, 33.8, 31.7, 25.7, 24.3, 14.8;
GCꢀMS (EI) m/z (%) 299 (9) [M+], 285 (11), 284 (54), 253 (14), 252 (71), 156 (5), 154 (24), 148 (20),
143 (16), 117 (28), 116 (35), 115 (12), 113 (10), 107 (38), 106 (15), 105 (17), 104 (31), 103 (14), 102
(26), 91 (37), 90 (11), 89 (24), 81 (19), 80 (15), 79 (100), 78 (12), 77 (29), 74 (10), 67 (27), 65 (13), 63
(11), 61 (21), 54 (10), 53 (18); HRMS (EI) m/z calcd. for C17H21N3S 299.1456, found 299.1448.
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1-{(1R*,2R*)-[4-(Methylthio)tetrahydrofuran-3-yl]}-4-phenyl-1H-1,2,3-triazole (3ca): Yellow
semisolid (116.2 mg, 89%); tr 17.52 min; Rf 0.49 (hexaneꢀEtOAc, 6:4); IR (neat) ν 3079, 2958, 2930,
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1459, 1419, 1219, 1077, 1049, 971, 760, 699 cm–1; H NMR (400 MHz, CDCl3) δ 7.90 (s, 1H), 7.87–
7.81 (m, 2H), 7.47–7.39 (m, 2H), 7.34–7.31 (m, 1H), 5.22 (dd, J = 7.0, 3.8 Hz, 1H), 4.51 (dd, J = 9.8,
7.7 Hz, 1H), 4.27 (d, J = 4.1 Hz, 2H), 3.66 (dd, J = 9.8, 6.4 Hz, 1H), 3.52 (ddd, J = 7.6, 6.5, 2.9 Hz,
1H), 2.26 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 148.6, 130.4, 128.9, 128.5, 125.8, 117.9, 72.8, 71.9,
67.5, 51.9, 15.5; GCꢀMS (EI) m/z (%) 261 (20) [M+], 188 (26), 156 (16), 146 (23), 145 (27), 143 (12),
130 (14), 128 (17), 118 (20), 117 (87), 116 (94), 115 (21), 103 (20), 102 (43), 91 (20), 90 (25), 89
(100), 77 (19), 76 (21), 75 (21), 74 (25), 71 (11), 69 (43), 68 (13), 64 (10), 63 (29), 62 (10), 61 (38), 54
(11), 51 (13); HRMS (EI) m/z calcd. for C13H15N3OS 261.0936, found 261.0939.
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1-{(1R*,2R*)-[5-(Methylthio)octan-4-yl]}-4-phenyl-1H-1,2,3-triazole (3da): Pale yellow solid (113.7
mg, 75%); m.p. 52.5–55.3 ºC; tr 17.26 min; Rf 0.43 (hexaneꢀEtOAc, 9:1); IR (neat) ν 3081, 2955, 2926,
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2868, 1460, 1429, 1221, 1081, 976, 765, 725 cm–1; H NMR (400 MHz, CDCl3) δ 7.97 (s, 1H), 7.91–
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7.84 (m, 2H), 7.46–7.39 (m, 2H), 7.36–7.29 (m, 1H), 4.16 (td, J = 9.4, 4.6 Hz, 1H), 2.88 (td, J = 9.4,
4.6 Hz, 1H), 2.24–2.11 (m, 1H), 2.05–1.95 (m, 1H), 1.99 (s, 3H), 1.64–1.54 (m, 2H), 1.53–1.45 (m,
1H), 1.44–1.35 (m, 1H), 1.29–1.19 (m, 2H), 0.93 (t, J = 7.2 Hz, 3H), 0.91 (t, J = 7.2 Hz, 3H); 13C NMR
(101 MHz, CDCl3) δ 147.4, 130.1, 128.9, 128.1, 125.7, 119.0, 65.2, 52.4, 34.5, 34.3, 20.4, 19.5, 15.6,
13.9, 13.8; GCꢀMS (EI) m/z (%) 303 (28) [M+], 260 (14), 228 (14), 201 (64), 200 (12), 186 (12), 173
(15), 172 (100), 143 (21), 130 (33), 129 (16), 121 (11), 118 (14), 117 (45), 116 (54), 115 (17), 111
(10), 110 (20), 104 (42), 103 (73), 102 (38), 91 (62), 90 (18), 89 (42), 86 (10), 81 (10), 77 (19), 76 (11),
69 (75), 63 (19), 61 (96), 55 (54); HRMS (EI) m/z calcd. for C17H25N3S 303.1769, found 303.1759.
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1-[2-(Methylthio)octyl]-4-phenyl-1H-1,2,3-triazole (3ea): Pale yellow solid (86.4 mg, 57%); m.p.
39.8–44.4 ºC; tr 19.41 min; Rf 0.66 (hexaneꢀEtOAc, 7:3); IR (neat) ν 3081, 2953, 2926, 2855, 1461,
1435, 1224, 1084, 977, 766, 727, 694 cm–1; 1H NMR (300 MHz, CDCl3) δ 7.90 (s, 1H), 7.88–7.81 (m,
2H), 7.47–7.39 (m, 2H), 7.37–7.29 (m, 1H), 4.55 (dd, J = 14.0, 6.2 Hz, 1H), 4.45 (dd, J = 14.0, 7.2 Hz,
1 H), 3.07–2.95 (m, 1H), 1.90 (s, 3H), 1.64–1.38 (m, 4H), 1.33–1.20 (m, 6H), 0.87 (t, J = 6.7 Hz, 3H);
13C NMR (75 MHz, CDCl3) δ 147.6, 130.6, 128.9, 128.3, 125.9, 120.8, 54.5, 47.6, 32.0, 31.8, 29.1,
26.8, 22.7, 14.2, 13.8; GCꢀMS (EI) m/z (%) 303 (15) [M+], 260 (26), 176 (20), 163 (10), 162 (13), 159
(67), 158 (11), 148 (18), 145 (19), 144 (24), 143 (37), 130 (26), 117 (25), 116 (32), 111 (20), 110 (12),
104 (31), 103 (26), 102 (29), 91 (14), 89 (26), 88 (18), 77 (18), 75 (14), 69 (93), 67 (13), 63 (14), 61
(100), 55 (79); HRMS (EI) m/z calcd. for C17H25N3S 303.1769, found 303.1760.
1-[1-(Methylthio)octan-2-yl]-4-phenyl-1H-1,2,3-triazole (3ea'): Yellow oil (28.8 mg, 19%); tr 19.01
min; Rf 0.69 (hexaneꢀEtOAc, 7:3); IR (neat) ν 2953, 2923, 2856, 1459, 1433, 1224, 762, 694 cm–1; 1H
NMR (300 MHz, CDCl3) δ 7.91–7.84 (m, 2H), 7.83 (s, 1H), 7.48–7.39 (m, 2H), 7.37–7.29 (m, 1H),
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4.63 (ddt, J = 8.9, 7.6, 5.7 Hz, 1H), 3.11–2.93 (m, 2H), 2.13–2.00 (m, 2H), 1.95 (s, 3H), 1.34–1.17 (m,
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8H), 0.85 (t, J = 6.8 Hz, 3H); C NMR (75 MHz, CDCl3) δ 147.5, 130.7, 128.9, 128.3, 125.9, 119.2,
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62.4, 39.9, 34.5, 31.6, 28.9, 26.0, 22.6, 16.4, 14.1; GCꢀMS (EI) m/z (%) 303 (17) [M+], 260 (28), 228
(12), 215 (10), 214 (63), 163 (23), 159 (36), 158 (71), 148 (36), 144 (24), 143 (21), 130 (26), 117 (50),
116 (52), 104 (43), 103 (31), 102 (30), 91 (35), 90 (16), 89 (32), 77 (12), 75 (10), 69 (86), 67 (13), 63
(15), 61 (100), 55 (60); HRMS (EI) m/z calcd. for C17H25N3S 303.1769, found 303.1779.
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1-[(1R*,2R*)-2-Methyl-2-(methylthio)cyclohexyl]-4-phenyl-1H-1,2,3-triazole (3fa): Pale yellow
solid (53.1 mg, 37%); m.p. 78.9–81.9 ºC; tr 19.89 min; Rf 0.53 (hexaneꢀEtOAc, 7:3); IR (KBr) ν 3117,
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2934, 2858, 1481, 1458, 1434, 1387, 1228, 1077, 979, 764, 697 cm–1; H NMR (400 MHz, CDCl3) δ
7.87–7.84 (m, 2H), 7.83 (s, 1H), 7.45–7.40 (m, 2H), 7.35–7.30 (m, 1H), 4.54 (dd, J = 12.0, 3.9 Hz,
1H), 2.39–2.29 (m, 1H), 2.09–2.03 (m, 1H), 2.01–1.95 (m, 2H), 1.86 (s, 3H), 1.81–1.73 (m, 2H), 1.72–
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1.66 (m, 2H), 1.35 (s, 3H); C NMR (101 MHz, CDCl3) δ 146.7, 130.9, 128.9, 128.1, 125.8, 120.6,
67.0, 48.1, 38.7, 29.0, 25.4, 21.9, 19.2, 10.8; GCꢀMS (EI) m/z (%) 287 (56) [M+], 288 (10) [M++1], 244
(18), 212 (21), 146 (22), 145 (14), 143 (49), 117 (17), 116 (25), 102 (18), 99 (14), 96 (13), 95 (100), 93
(10), 91 (13), 77 (11), 75 (11), 67 (23), 55 (16); HRMS (EI) m/z calcd. for C16H21N3S 287.1456, found
287.1462.
1-[(1R*,2R*)-1-Methyl-2-(methylthio)cyclohexyl]-4-phenyl-1H-1,2,3-triazole (3fa'): Yellow oil
(60.3 mg, 42%); tr 18.88 min; Rf 0.59 (hexaneꢀEtOAc, 7:3); IR (neat) ν 3130, 2928, 2862, 1458, 1448,
1234, 1025, 765, 699 cm–1; 1H NMR (400 MHz, CDCl3) δ 7.93 (s, 1H), 7.89–7.84 (m, 2H), 7.45–7.39
(m, 2H), 7.35–7.29 (m, 2H), 3.42 (dd, J = 11.9, 4.0 Hz, 1H), 2.64–2.54 (m, 1H), 2.16–2.12 (m, 2H),
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2.01–1.94 (m, 1H), 1.87–1.77 (m, 2H), 1.75 (s, 3H), 1.69 (s, 1H), 1.66–1.53 (m, 3H); C NMR (101
MHz, CDCl3) δ 146.6, 131.0, 128.9, 128.0, 125.7, 118.4, 66.3, 55.9, 39.4, 31.3, 25.9, 22.4, 19.1, 15.9;
GCꢀMS (EI) m/z (%) 287 (9) [M+], 244 (11), 212 (12), 144 (10), 143 (35), 142 (98), 117 (16), 116 (14),
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1-[2-(Methylthio)-1-phenylethyl]-4-phenyl-1H-1,2,3-triazole (3ga): White solid (131.3 mg, 89%);
m.p. 115.5–118.2 ºC; tr 19.24 min; Rf 0.62 (hexaneꢀEtOAc, 6:4); IR (neat) ν 3083, 2921, 2909, 1456,
1436, 1219, 1077, 763, 708, 700, 689 cm–1; 1H NMR (300 MHz, CDCl3) δ 7.87–7.79 (m, 2H), 7.75 (s,
1H), 7.49–7.29 (m, 8H), 5.74 (dd, J = 8.2, 6.7 Hz, 1H), 3.68 (dd, J = 14.0, 8.2 Hz, 1H), 3.37 (dd, J =
14.0, 6.7 Hz, 1H), 2.03 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 147.8, 137.8, 130.6, 129.3, 129.2, 128.9,
128.3, 127.3, 125.8, 119.6, 66.6, 39.3, 16.5; GCꢀMS (EI) m/z (%) 295 (7) [M+], 234 (26), 207 (14), 206
(74), 204 (14), 179 (10), 178 (31), 163 (15), 152 (13), 151 (60), 150 (100), 148 (15), 145 (28), 137
(12), 136 (30), 135 (47), 134 (16), 128 (12), 118 (10), 117 (20), 116 (51), 105 (11), 104 (59), 103 (45),
102 (27), 91 (45), 90 (13), 89 (37), 78 (15), 77 (42), 76 (13), 63 (21), 61 (14), 51 (18); HRMS (EI) m/z
calcd. for C17H17N3S 295.1143, found 295.1137.
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4-Hexyl-1-[2-(methylthio)-1-phenylethyl]-1H-1,2,3-triazole (3ge): White solid (116.7 mg, 77%);
m.p. 61.2–62.4 ºC; tr 17.91 min; Rf 0.69 (hexaneꢀEtOAc, 6:4); IR (neat) ν 3113, 3064, 2954, 2919,
2854, 1457, 1429, 1058, 851, 747, 704 cm–1; 1H NMR (300 MHz, CDCl3) δ 7.39–7.33 (m, 5H), 7.28 (s,
1H), 5.66 (dd, J = 8.2, 6.7 Hz, 1H), 3.60 (dd, J = 14.0, 8.2 Hz, 1H), 3.31 (dd, J = 14.0, 6.7 Hz, 1H),
2.70 (t, J = 7.7 Hz, 2H), 1.99 (s, 3H), 1.70–1.56 (m, 2H), 1.38–1.24 (m, 6H), 0.86 (t, J = 6.8 Hz, 3H);
13C NMR (75 MHz, CDCl3) δ 148.4, 138.1, 129.2, 129.0, 127.3, 120.7, 65.3, 39.4, 31.6, 29.4, 29.0,
25.8, 22.7, 16.3, 14.2; GCꢀMS (EI) m/z (%) 303 (1) [M+], 214 (24), 151 (49), 150 (100), 144 (12), 136
(21), 135 (35), 134 (13), 104 (40), 103 (25), 96 (10), 91 (43), 83 (13), 77 (15); HRMS (EI) m/z calcd.
for C17H25N3S 303.1769, found 303.1767.
1-[(Methylsulfinyl)(phenyl)methyl]-4-phenyl-1H-1,2,3-triazole (4ga): In a typical procedure,23
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roundꢀbottom flask was charged with sulfide 3ga (50.7 mg, 0.17 mmol), MeOH (1 mL) and the catalyst
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[0.1 mL of a solution prepared by mixing 96% H2SO4 (1.38 g) and 2ꢀpropanol (38 mL)]. H2O2 (0.05
mL, 0.50 mmol) was added at once to the stirred mixture and the progress of the oxidation was
followed by TLC (1–2 h). Water (10 mL) was added to the mixture after completion of the reaction.
The aqueous phase was saturated with NaCl and extracted with EtOAc (3 × 10 mL). The organic phase
was dried with MgSO4 and evaporated to give the pure sulfoxide 4ga (53.0 mg, 99%) as a ca. 1:1
diastereomeric mixture: white solid; m.p. 133.9–135.4 ºC; Rf 0.34 (EtOAc); IR (KBr) ν 3080, 2926,
1457, 1432, 1032, 1023, 975, 763, 714, 690 cm–1; 1H NMR (300 MHz, CDCl3) δ 7.91 (s, 1H), 7.85 (s,
1H), 7.84–7.87 (m, 16H), 6.20–6.11 (m, 2H), 4.30 (t, J = 12.6 Hz, 2H), 4.03 (dd, J = 13.2, 5.8 Hz, 2H),
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3.79 (dd, J = 13.2, 8.7 Hz, 2H), 3.34 (dd, J = 13.2, 2.9 Hz, 2H), 2.70 (s, 3H), 2.55 (s, 3H); C NMR
(75 MHz, CDCl3) δ 148.2, 137.6, 136.9, 130.0, 129.9, 129.8, 129.7, 129.6, 129.5, 129.4, 129.0, 128.6,
128.6, 127.3, 126.9, 126.8, 125.9, 121.2, 120.5, 60.2, 59.5, 58.8, 58.0, 39.2, 38.5; GCꢀMS (EI) m/z (%)
311 (2) [M+], 249 (10), 248 (57), 219 (10), 167 (10), 151 (22), 117 (13), 116 (100), 105 (13), 104 (77),
103 (23), 91 (13), 89 (21), 77 (14); HRMS (EI) m/z calcd. for C17H17N3OS 311.1092, found 311.1095.
4-Phenyl-1-(1-phenylvinyl)-1H-1,2,3-triazole (5ga): In a typical procedure, the sulfoxide 4ga (29.5
mg, 0.1 mmol) was heated in toluene at 120º C for 10 h in a pressure tube with a Teflon cap.
Evaporation of the solvent gave the pure triazole 5ga (22.0 mg, 90%) as a yellow oil. The physical and
spectroscopic data of 5ga were compared with those reported in the literature:21c 1H NMR (300 MHz,
CDCl3) δ 7.88–7.83 (m, 2H), 7.80 (s, 1H), 7.48–7.34 (m, 8H), 5.88 (d, J = 1.0 Hz, 1H), 5.57 (d, J = 1.0
13
Hz, 1H); C NMR (75 MHz, CDCl3) δ 147.7, 143.1, 134.8, 130.3, 130.1, 129.0, 128.5, 127.5, 125.9,
119.9, 109.6.
1-[(Methylsulfonyl)(phenyl)methyl]-4-phenyl-1H-1,2,3-triazole (6ga): In a typical procedure,24
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solution of mꢀchloroperbenzoic acid (86.3 mg, 0.50 mmol) in CH2Cl2 (2 mL) was added to a solution of
triazole 3ga (29.5 mg, 0.1 mmol) in CH2Cl2 (2 mL) at 0 ºC; the reaction was stirred at 0 ºC for 2 h.
Then, it was quenched with saturated aqueous sodium bicarbonate (10 mL) and diluted with CH2Cl2
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(10 mL). The organic layer was removed and the aqueous layer was extracted with CH2Cl2 (10 mL).
The combined organic layers were dried with MgSO4, the solvent was evaporated, and the crude
mixture was purified by column chromatography (silica gel, hexaneꢀEtOAc, 3:7)] to give the sulfone
6ga (28.4 mg, 87%) as a white solid; m.p. 164.7–167.7 ºC; tr 21.85 min; Rf 0.52 (hexaneꢀEtOAc, 1:1);
IR (KBr) ν 3093, 2923, 1335, 1302, 1149, 1129, 1051, 1088, 1051, 976, 747, 696, 669 cm–1; 1H NMR
(400 MHz, CDCl3) δ 7.88 (s, 1H), 7.84–7.71 (m, 2H), 7.46–7.32 (m, 8H), 6.14 (dd, J = 9.7, 4.0 Hz,
1H), 4.78 (dd, J = 15.2, 9.7 Hz, 1H), 3.74 (dd, J = 15.2, 4.0 Hz, 1H), 2.56 (s, 3H); 13C NMR (101 MHz,
CDCl3) δ 148.6, 136.7, 129.8, 129.8, 129.7, 129.1, 128.8, 126.9, 125.9, 120.8, 60.8, 59.5, 42.4; GCꢀMS
(EI) m/z (%) 327 (5) [M+], 207 (23), 206 (12), 183 (13), 117 (15), 116 (100), 105 (11), 104 (54), 103
(16), 102 (10), 91 (16), 89 (17), 77 (11); HRMS (EI) m/z calcd. for C17H17N3O2S 327.1041, found
327.1042.
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4-Phenyl-1H-1,2,3-triazole (7a) and (E)-[2-(methylsulfonyl)vinyl]benzene (8a): In a typical
procedure,25 a solution of compound 6ga (50.0 mg, 0.15 mmol) in dry MeOH (1 mL) and THF (0.5
mL) was added to a stirred suspension of Na/Hg [freshly prepared from Na (70.0 mg, 3.0 mmol) and
Hg (1.163 g, 5.8 mmol)] and Na2HPO4 (428 mg, 3.0 mmol) in MeOH (2 mL) under argon. The reaction
progress was monitored by TLC and GLC. The mixture was then filtered and the filter cake was
washed with Et2O. The combined filtrate was evaporated under vacuum and purified by preparative
TLC (hexaneꢀEtOAc, 1:1) to give triazole 7a (21.7 mg, 99%) and vinyl sulfone 8a (27.3 mg, 99%) as
colorless solids in quantitative yields. The physical and spectroscopic data of 7a26 and 8a27 were in
agreement with those reported in the literature.
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ASSOCIATED CONTENT
Supporting information
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1H and 13C NMR spectra and some GLCꢀMS analyses. This material is free of charge via the Internet at
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http://pubs.acs.org.
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AUTHOR INFORMATION
Corresponding author
*Eꢀmail: falonso@ua.es
ACKNOWLEDGEMENTS
This work was generously supported by the Spanish Ministerio de Economía y Competitividad
(MINECO; CTQ2007ꢀ65218, CTQ2011ꢀ24151 and Consolider Ingenio 2010ꢀCSD2007ꢀ00006), the
Generalitat Valenciana (GV; PROMETEO/2009/039), and Fondo Europeo de Desarrollo Regional
(FEDER). Y. M. acknowledges the Instituto de Síntesis Orgánica (ISO) of the Universidad de Alicante
for a grant.
REFERENCES
(1) For a review, see: Kolb, H. C.; Finn, M. G.; Sharpless, K. B. Angew. Chem. Int. Ed. 2001, 40,
2004.
(2) (a) Wang, Q.; Hawker, C. Chem. Asian J. 2011, 6, 2568. (b) For a recent special issue, see: Chem.
Asian J. 2011, 6, issue nº 10.
(3) (a) Tornøe, C. W.; Christensen, C.; Meldal, M. J. Org. Chem. 2002, 67, 3057. (b) Rostovtsev, V.
V.; Green, L. G.; Fokin, V. V.; Sharpless, K. B. Angew. Chem. Int. Ed. 2002, 41, 2596.
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(4) For selected reviews, see: (a) Meldal, M.; Tornøe, C. W. Chem. Rev. 2008, 108, 2952. (b) Fokin,
V. V. In Organic Chemistry. Breakthroughs and Perpectives, 1st Edn.; Ding, K.; Dai, L.ꢀX., Eds.;
WileyꢀVCH: Weinheim, 2012, Chapter 7.
6
7
8
9
(5) For some recent examples, see: (a) Kumar, D.; Patel, G.; Buchi Reddy, V. Synlett 2009, 399. (b)
Bénéteau, V.; Olmos, A.; Boningari, T.; Sommer, J.; Pale, P. Tetrahedron Lett. 2010, 51, 3673. (c)
Yan, J.; Wang, L. Synthesis 2010, 447. (d) T. Shamim, S. Paul, Catal. Lett. 2010, 136, 260.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
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33
34
35
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42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(6) (a) Zhang, F.; Moses, J. E. Org. Lett. 2009, 11, 1587 and references cited therein. (b) Smith, N. M.;
Greaves, M. J.; Jewell, R.; Perry, M. W. D.; Stocks, M. J.; Stonehouse, J. P. Synlett 2009, 1391. (c)
Suárez, J. R.; Trastoy, B.; Pérez Ojeda, E.; MarínꢀBarrios, R.; Chiara, J. L. Adv. Synth. Catal.
2010, 352, 2515.
(7) (a) Surendra Reddy, P.; Sreedhar, B. Synthesis 2009, 4203. (b) Kumar, D.; Buchi Reddy, V.;
Varma, R. S. Tetrahedron Lett. 2009, 50, 2065.
(8) Kumar, D.; Buchi Reddy, V. Synthesis 2010, 1687.
(9) See, for instance: (a) Kumaraswamy, G.; Ankamma, K.; Pitchaiah, A. J. Org. Chem. 2007, 72,
9822. (b) Rajender Reddy, K.; Uma Maheswari, C.; Rajgopal, K.; Lakshmi Kantam, M. Synth.
Commun. 2008, 38, 2158. (c) Sharghi, H.; Beyzavi, M. H.; Safavi, A.; Doroodmand, M. M.;
Khalifeh, R. Adv. Synth. Catal. 2009, 351, 2391. (d) T. Boningari, A. Olmos, B. M. Reddy, J.
Sommer, P. Pale, Eur. J. Org. Chem. 2010, 6338.
(10) Zhang, J.; Wu, J.; Shen, L.; Cao, S. Adv. Synth. Catal. 2011, 353, 580.
(11) (a) Tao, C.ꢀZ.; Cui, X.; Li, J.; Liu, A.ꢀX.; Liu, L.; Guo, Q.ꢀX. Tetrahedron Lett. 2007, 48, 3525. (b)
Mohammed, S.; Padala, A. K.; Dar, B. A.; Singh, B.; Sreedhar, B.; Vishwakarma, R. A.; Bharate,
S. B. Tetrahedron 2012, 68, 8156.
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(12) Attanasi, O. A.; Favi, G.; Filippone, P.; Mantellini, F.; Moscatelli, G.; Perrulli, F. R. Org. Lett.
2010, 12, 468.
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7
8
9
(13) For a review, see: Jin, T.; Yan, M.; Yamamoto, Y. ChemCatChem 2012, 4, 1217.
(14) For a recent review, see: Alonso, F.; Riente, P.; Yus, M. Acc. Chem. Res. 2011, 44, 379.
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(15) (a) Alonso, F.; Vitale, C.; Radivoy, G.; Yus, M. Synthesis 2003, 443. (b) Alonso, F.; Moglie, Y.;
Radivoy, G.; Vitale, C.; Yus, M. Appl. Catal. A: Gen. 2004, 271, 171. (c) Radivoy, G.; Alonso, F.;
Moglie, Y.; Vitale, C.; Yus, M. Tetrahedron 2005, 61, 3859.
(16) (a) Alonso, F.; Moglie, Y.; Radivoy, G.; Yus, M. Tetrahedron Lett. 2009, 50, 2358. (b) Alonso, F.;
Moglie, Y.; Radivoy, G.; Yus, M. Eur. J. Org. Chem. 2010, 1875.
(17) (a) Alonso, F.; Moglie, Y.; Radivoy, G.; Yus, M. Adv. Synth. Catal. 2010, 352, 3208. (b) Alonso,
F.; Moglie, Y.; Radivoy, G.; Yus, M. Org. Biomol. Chem. 2011, 9, 6385. (c) Alonso, F.; Moglie,
Y.; Radivoy, G.; Yus, M. J. Org. Chem. 2011, 76, 8394. (d) Alonso, F.; Moglie, Y.; Radivoy, G.;
Yus, M. Heterocycles 2012, 84, 1033.
(18) Trost, B. M.; Shibata, T. J. Am. Chem. Soc. 1982, 104, 3225.
(19) (a) Helmkamp, G. K.; Olsen, B. A.; Pettitt, D. J. J. Org. Chem. 1965, 30, 676. (b) Helmkamp, G.
K.; Cassey, H. N.; Olsen, B. A.; Pettitt, D. J. J. Org. Chem. 1965, 30, 933.
(20) See, for instance: (a) Zhu, Y. W.; Yi, W.ꢀB.; Cai, C. Catal. Commun. 2011, 15, 118. (b) Michaels,
H. A.; Zhu, L. Chem. Asian J. 2011, 6, 2825.
(21) (a) L’Abbé, G.; Hassner, A. J. Heterocycl. Chem. 1970, 7, 361. (b) Duan, H.; Yan, W.; Sengupta,
S.; Shi, X. Bioorg. Med. Chem. Lett. 2009, 19, 3899. (c) Kupracz, L.; Hartwig, J.; Wegner, J.;
Ceylan, S.; Kirschning, A. Beilstein J. Org. Chem. 2011, 7, 1441.
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(22) The argon atmosphere was used as a precautionary measure because of the gas evolution during
the reaction (the flash point of Me2S is –36 ºC). The reaction also proceeds under air.
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(23) Drabowicz, J.; Lyzwa, P.; Popielarczk, M.; Mikolajczyk, M. Synthesis 1990, 937.
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(24) Evans, D. A.; Faul, M. M.; Colombo, L.; Bisaha, J. J.; Clardy, J.; Cherry, D. J. Am. Chem. Soc.
1992, 114, 5977.
(25) Enders, D.; Jandeleit, B.; Prokopenko, O. F. Tetrahedron 1995, 51, 6273.
(26) Kim, J. D.; Palani, T.; Kumar, M. R.; Lee, S.; Choi, H. C. J. Mater. Chem. 2012, 22, 20665.
(27) Yuan, G.; Zheng, J.; Gao, X.; Li, X.; Huang, L.; Chen, H.; Jiang, H. Chem. Commun. 2012, 48,
7513.
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