Synthesis of 5-organostibano-1H-1,2,3-triazoles by Cu-catalyzed azide-alkyne cycloaddition and their application in the acyl-induced deantimonation for the preparation of fully substituted 5-acyl-1,2,3-triazoles

Article abstract of DOI:10.1016/j.tet.2017.03.046

The Cu-catalyzed azide-alkyne cycloaddition by the reaction of various ethynylstibanes with benzylazide in the presence of CuBr (5?mol%) under aerobic conditions led to the formation of trisubstituted 5-organostibano-1H-1,2,3-triazoles. Further, the acyl-induced deantimonation of 5-stibanotriazoles with acyl chlorides in the presence of N,N-dimethyl-4-aminopyridine and triethylamine afforded the corresponding trisubstituted 5-acyltriazoles in moderate-to-good yields.

Full text of DOI:10.1016/j.tet.2017.03.046

Tetrahedron xxx (2017) 1e9
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Synthesis of 5-organostibano-1H-1,2,3-triazoles by Cu-catalyzed
azide-alkyne cycloaddition and their application in the acyl-induced
deantimonation for the preparation of fully substituted 5-acyl-1,2,3-
triazoles
Mizuki Yamada a, Mio Matsumura a, Yuki Murata a, Masatoshi Kawahata b, Kohki Saito a,
,
*
Naoki Kakusawa c, Kentaro Yamaguchi b, Shuji Yasuike a
a School of Pharmaceutical Sciences, Aichi Gakuin University, 1-100 Kusumoto-cho, Chikusa-ku, Nagoya 464-8650, Japan
b Pharmaceutical Sciences at Kagawa Campus, Tokushima Bunri University, 1314-1 Shido, Sanuki, Kagawa 769-2193, Japan
c Faculty of Pharmaceutical Sciences, Hokuriku University, Ho-3 Kanagawa-machi, Kanazawa 920-1181, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
The Cu-catalyzed azide-alkyne cycloaddition by the reaction of various ethynylstibanes with benzylazide
in the presence of CuBr (5 mol%) under aerobic conditions led to the formation of trisubstituted 5-
organostibano-1H-1,2,3-triazoles. Further, the acyl-induced deantimonation of 5-stibanotriazoles with
acyl chlorides in the presence of N,N-dimethyl-4-aminopyridine and triethylamine afforded the corre-
sponding trisubstituted 5-acyltriazoles in moderate-to-good yields.
Received 20 January 2017
Received in revised form
13 March 2017
Accepted 15 March 2017
Available online xxx
© 2017 Elsevier Ltd. All rights reserved.
Keywords:
Ethynylstibane
Cu-catalyzed azide-alkyne cycloaddition
Antimony
Acyl-induced deantimonation
Acylation
1,2,3-Triazole
1. Introduction
be used for the synthesis of chiral organoantimony compounds by
nucleophilic displacement reactions with Grignard or organo-
The chemistry of organoantimony compounds has been devel-
oped and the potential of such compounds in organic synthesis is
always increasing.1 With regard to the application of trivalent
organoantimony compounds (stibanes), a wide variety of reactions
like self-coupling reactions,2 cross-coupling reactions,3 photore-
actions,4 oxidations,5 and asymmetric reactions with optically
active organoantimony compounds6 have been reported during the
last three decades. Recently, we reported that trivalent organo-
antimony compounds bearing alkynyl groups are useful trans-
metallating agents for Pd-catalyzed cross-coupling reactions with
organic halides.7 In particular, they could be coupled to acyl chlo-
rides, aryl and vinyl halides to afford the corresponding ethy-
nylketones, diarylacetylenes, and 1,3-enynes. Moreover, they could
lithium reagents; the ethynyl groups on the antimony atom serve as
moderate leaving groups.8 Stibane reagents, such as triphenyl-
stibane, have low toxicity,9 and therefore are promising organic
synthetic reagents.
The copper-catalyzed azide-alkyne [3þ2] cycloaddition reaction
(CuAAC) is widely used for the synthesis of 1,2,3-triazoles because
of its excellent regioselectivity and rapid reaction rate10; the reac-
tion has also been applied in the fields of biology,11 and material
science.12 The regioselectivite CuAAC synthesis of fully substituted
5-hetero-1,2,3-triazoles having group 15 and 16 elements such as
phosphorus (P),13 bismuth (Bi),14 sulfur (S),15 selenium (Se),15,16 and
tellurium (Te)17 has been reported. Among these, further derivati-
zation of the 5-position, based on the reactivity of the group 15 and
16 heteroatoms, was carried out only for 5-bismuthano-14 and 5-
tellanyltriazole17,18 derivatives. Fokin et al. reported the synthesis
of 5-bismuthano-1,2,3-triazoles by reacting ethynylbismuthanes
with organic azides using CuOTf (5 mol%).14 Further
* Corresponding author.
E-mail address: s-yasuik@dpc.agu.ac.jp (S. Yasuike).
http://dx.doi.org/10.1016/j.tet.2017.03.046
0040-4020/© 2017 Elsevier Ltd. All rights reserved.
Please cite this article in press as: Yamada M, et al., Synthesis of 5-organostibano-1H-1,2,3-triazoles by Cu-catalyzed azide-alkyne cycloaddition
and their application in the acyl-induced deantimonation for the preparation of fully substituted 5-acyl-1,2,3-triazoles, Tetrahedron (2017),
http://dx.doi.org/10.1016/j.tet.2017.03.046

2
M. Yamada et al. / Tetrahedron xxx (2017) 1e9
functionalization with electrophiles like acyl chlorides, diphosgene,
sulfuryl chloride, and halogens generated the corresponding fully
substituted 1,2,3-triazoles after elimination of the bismuth group at
the 5-position. Stefani et al. reported the reaction of alkyl phenyl-
ethynyl tellurides with organic azides using CuI (1 eq) and pen-
tamethyldiethylenetriamine (1 eq) to form 5-tellanyl-1,2,3-
triazoles.17 Further derivatization was achieved using Sonoga-
shira- and Suzuki-type cross-coupling reactions and Te-Li exchange
reaction at the 5-position of the triazoles.17,18 However, these re-
actions have a drawback at the cycloaddition step: while the
cycloaddition of bismuth compounds required alkyne derivatives
based on the phenothiabismuthane-5,5-dioxide framework for
stabilization, the cycloaddition of tellurium compounds required
stoichiometric amounts of the Cu reagent and base. Recently, we
have reported the synthesis of fully substituted 5-organostibano-
1,2,3-triazoles by the Cu-catalyzed AAC of an ethynylstibane,
(phenylethynyl)di-p-tolylstibane, with organic azides.19 Herein, we
reported the complete results of the Cu-catalyzed AAC of various
ethynylstibanes (2) with benzylazide (3) under mild and simple
reaction conditions and their further acylation for the preparation
of fully substituted 5-acyl-1,2,3-triazoles (6e17).
nature (electron-rich or electron-poor) of the substituents on the
phenyl group in the ethynyl moiety (2a-e) did not affect the
outcome of the reaction. Interestingly, the ethynylstibane (2j)
having a silyl moiety gave the expected product 4j with the silyl
20
ꢀ
group intact. This result was inconsistent with Pericas's report,
where the CuAAC reaction of 1-trimethylsilyl-1-alkynes afforded
5H-triazoles with desilylation.
The regiochemistry of 5-stibanotriazoles (4a-j) was elucidated
by 1H NMR and confirmed by single-crystal X-ray analysis. A nu-
clear Overhauser effect (NOE) was observed between the benzyl
protons and the aromatic protons of the antimony p-tolyl groups.
Fig. 1 shows the crystal structure of compound 4g as a represen-
tative example of 5-stibanotriazoles (4) and Table 3 shows the
selected bond lengths and angles. The single-crystal X-ray analysis
of compound 4g revealed the presence of an intramolecular inter-
action between the antimony and nitrogen atoms (Fig. 1 red line),
with an SbeN distance of 2.953(4) Å. This was consistent with 82%
of the sum of the van der Waals radii (3.60 Å) of the two elements,
and equivalent to 143% of the covalent bond length (2.07 Å).21 The
central antimony exhibited a pseudo trigonal bipyramidal (TBP)
structure. The C(22) on the tolyl group and the nitrogen on the
pyridine ring were approximately trans to each other with an N(4)
eSbeC(22) bond angle of 160.27(13)ꢀ. These observations indicate
that the C1eSb bond on the triazole and the C15eSb bond on the
tolyl group occupy the equatorial positions together with the lone
pair of electrons on the antimony atom, and that the N/Sb intra-
molecular interaction and the C22eSb bond on the tolyl group
2. Results and discussion
2.1. Preparation of ethynylstibanes (2) and Cu-catalyzed azide-
alkyne cycloaddition of 2 with benzyl azide (3)
occupy the apical positions (Table 3). Moreover, a
p-p interaction
The key starting compounds, ethynylstibanes (2a-j), were pre-
pared by a modified method previously reported by us.7b Thus,
treatment of terminal alkynes (1a-j) with n-BuLi, in dry diethyl
ether under an argon atmosphere at 0 ꢀC, followed by the addition
of bis(4-methylphenyl)antimony bromide affords arylethynyl,
vinylethynyl, alkylethynyl, and silylethynyl compounds (2a-j) in
moderate-to-good yields (Table 1).
We have previously reported that the Cu-catalyzed [3þ2]
regioselective cycloaddition of ethynylstibane (2c) with an organic
azides, in the presence of 5 mol% CuBr in THF at 60 ꢀC and under
aerobic conditions, generates 5-stibano-1,2,3-triazoles.19 In order to
investigate the efficiency and generality of this reaction, various
ethynylstibanes (2a-j) were reacted with benzylazide (3) under the
above optimal experimental conditions. The results are summa-
rized in Table 2. Ethynylstibanes with functional groups such as aryl
(2a-e), heteroaryl (2f, g), vinyl (2h) and alkyl (2i) afforded the
corresponding products in good-to-excellent yields. The electronic
was observed between one tolyl group on the antimony atom and
the benzyl group. These rings adopt a parallel-displaced structure,
with distances of 3.755 Å between the centroids of the two phenyl
rings (Fig. 1 blue line).
A possible mechanism of the present Cu-catalyzed cycloaddition
is shown in Scheme 1. The catalytic cycle of this reaction would be
similar to that of the reaction of 1-iodoalkynes22 and 1-
bismuthanoalkynes14 with organic azides. As shown in cycle A,
the initial step would be the generation of
p-complex A from the
reaction between the Cu(I) catalyst and ethynylstibane 2. Coordi-
nation of complex A with organic azides would give complex B,
which after cyclization via a vinylidene-like transition state C,
would give 5-stibanotriazole 4. An alternative cycle B via copper
acetylide D and 5-copper triazole E is also possible. The reaction of
2c without benzylazide 3 in the presence of 5 mol% CuBr in THF at
60 ꢀC under aerobic conditions recovered 2c at isolated yield of 82%
(Scheme 2a). In this reaction, formation of ethynylbenzene was
slightly observed in gas-liquid chromatography and 1,4-
diphenylbuta-1,3-diyne was not detected. Moreover, the cross-
over reaction of a 1: 1: 2 mixture of 2c (0.5 mmol), 1b (0.5 mmol),
and 3 (1 mmol) under the optimized condition gave 4c and 1-
benzyl-4-p-tolyl-1,2,3-triazole in 79% and 28%, respectively
(Scheme 2b). It seems that p-Tol2SbBr F was not generated in this
crossover reaction. Furthermore, organoantimony compounds such
as ethynylstibane 2c and 5-stibanotriazole 4c seem to be
obstructing generation of 1-benzyl-4-p-tolyl-1,2,3-triazole and/or
5-copper triazole in this reaction. Standard CuAAC of 1-ethynyl-4-
methylbenzene 1b with benzylazide 3 without ethynylstibane 2c
afforded 1-benzyl-4-p-tolyl-1,2,3-triazole in 88%. These results
suggest that cycle A acts on predominance than cycle B. However,
the detailed reaction mechanism is unclear at present. An investi-
gation of the reaction mechanisms including regioselectivity is in
progress.
Table 1
Preparation of ethynylstibanes 2.
Entry
R
Yield (%)a
1
2
3
4
5
6
7
8
9
4-Methoxyphenyl
4-Methylphenyl
Phenyl
4-Bromophenyl
4-Trifluoromethylphenyl
2-Thienyl
2-Pyridyl
1-Cyclohexenyl
n-Butyl
2a: 75
2b: 70
2c: 82
2d: 68
2e: 66
2f: 55
2g: 58
2h: 52
2i: 51
2j: 63
2.2. Reaction of 5-stibanotriazoles with acyl chlorides
10
Trimethylsilyl
a
Isolated yield.
Insertion of different carbon chain at all positions of the
Please cite this article in press as: Yamada M, et al., Synthesis of 5-organostibano-1H-1,2,3-triazoles by Cu-catalyzed azide-alkyne cycloaddition
and their application in the acyl-induced deantimonation for the preparation of fully substituted 5-acyl-1,2,3-triazoles, Tetrahedron (2017),
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M. Yamada et al. / Tetrahedron xxx (2017) 1e9
3
Table 2
Cu-catalyzed [3þ2] cycloaddition of 2 with benzyl azide 3.a,b
4a: 92% (6 h)
4b: 85% (6 h)
4c: 93% (6 h)
4d: 78% (9 h)
4e: 84% (9 h)
4f: 63% (9 h)
4g: 64% (3 h)
4h: 77% (7 h)
4i: 87% (2 h)
4j: 78% (5 h)
a
2 (0.5 mmol), 3 (0.5 mmol), CuBr (0.025 mmol).
Isolated yield.
b
component reaction by copper acetylide, benzylazide and acyl
chloride in 2013.23 However, one of the component, copper-
acetylide was complicated to synthesize and hard to handle.
Recently, we reported the synthesis of ArBCl2 by a boron-induced
ipso-deantimonation of triarylstibanes with boron halides as elec-
trophiles, which were then transformed to arylboronates.24
Furthermore, the iron-catalyzed reactions of tris(2-thienyl)sti-
banes with acyl chlorides give ipso-substituted acylthiophenes.25
Therefore, we investigated whether 5-stibanotriazole (4) could be
converted into 1,4,5-trisubstituted 5-acyl-1,2,3-triazoles by an acyl-
induced deantimonation. Optimization experiments were con-
ducted using 4c and benzoyl chloride (5a) as model substrates, and
the results are summarized in Table 4. The reaction of 4c with 5a in
the presence of Lewis acids (10 mol%) such as BF3$OEt2, AlCl3, TiCl4
or FeCl3 in 1,2-DCE at room temperature gave complex mixtures
(Table 4, entries 1e5). Because the benzoylation of 5-
bismuthanotriazole with benzoyl chloride (5a) using N,N-
dimethyl-4-aminopyridine (DMAP) and triethylamine (TEA) as
additives is known,14 we applied this reaction in our reaction sys-
tem. Using the optimal ratio of 5a, DMAP and TEA of 4: 1: 4 found
for the benzoylation of 5-bismuthanotriazole. The 5-stibanotriazole
(4c) was converted to the corresponding product (6) in 63% yield
(Table 4, entry 6) after 20 h at 80 ꢀC in DCE. We then determined the
optimum amounts of 5a, DMAP, and TEA (Table 4, entries 6e12) for
our system; employing 1.2 equiv. of 5a, 1 equiv. of DMAP, and 1.2
equiv. of TEA gave the best result (Table 4, entry 8). A possible by-
product, 4-methylbenzophenone, obtainable from the acylation at
the antimony 4-metylphenyl group of 5a, was not observed. To
investigate the scope of the reaction, 5-stibanotriazoles (4a-c, e, i)
were treated with various acyl chlorides (5) under the standard
conditions (Table 5). The reaction of 4c with aromatic acyl chlorides
(5a-g) afforded the corresponding 5-acyl-triazoles (6e12) in
moderate to good yields (Table 5, entries 1e7). Among these,
benzoyl chlorides containing electron-donating substituents on the
benzene ring, such as methoxy group, exhibited lower reactivities.
Unfortunately, the reaction of 4c with aliphatic acyl chloride such
as valeroyl chloride (5h) did not afford 13 (Table 5, entry 8). Next,
we treated various 5-stibanotriazoles (4a, b, e, i) with benzoyl
chloride (5a) under the same reaction conditions. All these
Fig. 1. Molecular structures of 4g with 50% probability thermal ellipsoids. Red line
shows hyper valent interaction and blue line shows intramolecular
between the centroids of the two phenyl rings.
p-p interaction
Table 3
Selected bond length (Å) and bond angles (ꢀ) for 4g.
Bond lengths
SbeC1
SbeC15
SbeC22
SbeN4
2.170(4)
2.136(4)
2.165(4)
2.953(4)
Bond angles
C1eSbeC15
C1eSbeC22
C15eSbeC22
C1eSbeN4
C15eSbeN4
C22eSbeN4
96.82(15)
98.00(15)
94.32(15)
66.62(4)
76.22(13)
160.27(13)
aromatic heterocycles is a challenging theme. Wang and Hu re-
ported the synthesis of 1,4,5-trisubstituted-1,2,3-triazoles such as
1-benzyl-4-aryl-5-acyl-1,2,3-triazole using the one-pot three
Please cite this article in press as: Yamada M, et al., Synthesis of 5-organostibano-1H-1,2,3-triazoles by Cu-catalyzed azide-alkyne cycloaddition
and their application in the acyl-induced deantimonation for the preparation of fully substituted 5-acyl-1,2,3-triazoles, Tetrahedron (2017),
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4
M. Yamada et al. / Tetrahedron xxx (2017) 1e9
Scheme 1. Possible mechanism.
Scheme 2. Control experiments.
Table 4
reactions afforded the corresponding 5-acyl-triazoles (14e17)
Screening of acylation.a
(Table 5, entries 9e12). 5-Stibanotriazles (4a, b, e, i) having
electron-donating groups on the phenyl ring such as methoxy (4a),
or alkyl group at the 4-position (4i) gave better results than those
with electron-withdrawing groups (4e).
The reaction mechanism of the acylation of 5-stibanotriazoles
(4) with acyl chlorides (5) is unclear at present. We consider that
the mechanism would be similar to that of the pyridine-catalyzed
acylation of alcohols and amines proposed by Zipse,26 or the
transmetallation of triarylstibanes into arylboronates,24 and the
reaction of tris(2-thienyl)stibanes with acyl chlorides, both pro-
posed by us.25 A possible mechanism for the reaction between 5-
stibanotriazoles and acyl chlorides to form of 5-acyltriazoles is
depicted in Scheme 3. In the initial step, DMAP reacts with the acyl
donor to form N-acylpyridine (A). Next, the electrophilic attack of A
onto the 5-position of triazoles would form intermediate B. Finally,
the chloride ion attacks the antimony to generate 5-acyl-triazoles,
p-Tol2SbCl, and DMAP. As diphenylantimony halides are known to
react with pyridine to form antimony-pyridine complexes,27 we
speculate that the eliminated DMAP and p-Tol2SbCl form the
complex C, which would account for the requirement of a full
equivalent of DMAP in the reaction.
Entry
5a (eq)
Additive (eq)
Base (eq)
Yield (%)
1
2
3
4
5
6
7
8
1.2
1.2
1.2
1.2
1.2
4.0
2.0
1.2
1.2
1.2
1.2
1.2
BF3$OEt2 (0.1)
AlCl3 (0.1)
TiCl4 (0.1)
ZnCl2 (0.1)
FeCl3 (0.1)
DMAP (1)
DMAP (1)
DMAP (1)
DMAP (0.3)
DMAP (1.2)
e
e
0
0
0
0
e
e
e
e
0
TEA (4)
TEA (2)
TEA (1.2)
TEA (1.2)
e
63
73
76
38
35
15
0
9
10
11
12
TEA (1.2)
e
e
a
Isolated yield.
Please cite this article in press as: Yamada M, et al., Synthesis of 5-organostibano-1H-1,2,3-triazoles by Cu-catalyzed azide-alkyne cycloaddition
and their application in the acyl-induced deantimonation for the preparation of fully substituted 5-acyl-1,2,3-triazoles, Tetrahedron (2017),
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M. Yamada et al. / Tetrahedron xxx (2017) 1e9
5
Table 5
triazoles was developed by employing the acyl-induced dean-
timonation of 5-stibanotriazoles with acyl chlorides in the presence
of DMAP and TEA. Detailed mechanistic studies of these reactions
and functionalization of 5-stibanotriazoles with other electrophiles
are currently in progress and will be reported in the future.
Reaction of 5-stibanotriazole 4 with acyl chlorides 5.a,b
4. Experimental
Entry
1
4
R1
5
R2
Product
Yield (%)
4.1. General information
4c
5b
7: 46
Melting points were measured on a Yanagimoto micro melting
point hot-stage apparatus (MP-S3) and reported as uncorrected
values. 1H NMR (TMS:
d
: 0.00 or CH2Cl2: 5.30 ppm as an internal
2
3
4
5
4c
4c
4c
4c
5c
5a
5d
5e
8: 64
6: 76
9: 72
10: 79
standard) and 13C NMR (CDCl3:
d
: 77.00 ppm as an internal stan-
dard) spectra were recorded on JEOL JNM-AL400 (400 MHz and
100 MHz) spectrometers in CDCl3. Mass spectra were obtained on a
JEOL JMP-DX300 instrument (70 eV, 300
mA). IR spectra were
recorded on a Shimadzu FTIR-8400S spectrophotometer and re-
ported in terms of frequency of absorption (cmꢁ1). Only selected IR
bands are reported. Chromatographic separations were carried out
using Silica Gel 60N (Kanto Chemical Co., Inc.) under the solvent
system stated. Thin-layer chromatography (TLC) was performed
using Merck Pre-coated TLC plates (silica gel 60 F254). Each re-
agents were purchased from Sigma-Aldrich Japan, Wako Pure
Chemical Industries and Tokyo Chemical Industry Co., Ltd.
4.2. Preparation of ethynylstibanes (2)
6
7
8
9
4c
4c
4c
4a
5f
11: 77
12: 76
13: 0
An diethyl ether solution of di-p-tolylantimony(III) bromide
(15 mmol, 15 mL), synthesized from redistribution of tri-
tolylstibane (4.0 g, 10 mmol, 2 eq.) and tribromoantimony (1.8 g,
5 mmol) was added dropwise at 0 ꢀC to an diethyl ether solution
(10 mL) of lithium acetylide, prepared from the appropriate acet-
ylene (10 mmol, 2 eq.) and n-butyllithium (1.54 M solution in
hexane, 6.5 mL, 10 mmol) under argon. After stirring the mixture at
the same temperature for 2 h, the reaction mixture was diluted
with diethyl ether (50 mL) and quenched with water. The reaction
mixture was separated and the aqueous layer was extracted with
diethyl ether (50 mL). The combined organic layer was dried over
anhydrous MgSO4, and concentrated under reduced pressure. The
residue was purified by silica gel chromatography (n-hexane/
CH2Cl2) or recrystallization.
5g
5h
5a
14: 75
10
11
4b
4e
4i
5a
5a
5a
15: 64
16: 55
17: 76
4.2.1. 4-Methoxyphenylethynyldi-p-tolylstibane (2a)
Colorless needle (3.26 g, 75% yield), mp 79e80 ꢀC (from Et2O-
MeOH). 1H NMR (400 MHz, CDCl3)
d
: 7.59 (4H, d, J ¼ 7.8 Hz), 7.43
(2H, d, J ¼ 6.7 Hz), 7.15 (4H, d, J ¼ 7.8 Hz), 6.82 (2H, d, J ¼ 7.8 Hz),
3.81 (3H, s), 2.30 (6H, s). 13C NMR (100 MHz, CDCl3)
: 159.7 (s),
138.6 (s), 135.4 (d), 134.5 (s), 133.4 (d), 129.7 (d), 115.5 (s), 113.8 (d),
d
111.0 (s), 84.1 (s), 55.2 (q), 21.3 (q). FTIR (KBr) n
: 2135 cmꢁ1. LRMS
(EI) m/z: 434 (Mþ, 90), 313 (40), 222 (100), 212 (70), 91 (40). HRMS:
m/z [M]þ calcd for C23H21OSb: 434.0631. Found: 434.0640.
12
4.2.2. 4-Tolylethynyldi-p-tolylstibane (2b)
Colorless needle (2.93 g, 70% yield), mp 85e87 ꢀC (from Et2O-
a
EtOH). 1H NMR (400 MHz, CDCl3)
d
: 7.61 (4H, d, J ¼ 7.8 Hz), 7.40 (2H,
d, J ¼ 7.8 Hz), 7.16 (4H, d, J ¼ 7.3 Hz), 7.11 (2H, d, J ¼ 7.8 Hz), 2.35 (3H,
s), 2.33 (6H, s). 13C NMR (100 MHz, CDCl3)
: 138.6 (s), 135.5 (d),
134.5 (s), 131.9 (d), 129.7 (d) 128.9 (d), 120.3 (s), 111.2 (s), 85.1 (s),
21.5 (q), 21.3 (q). FTIR (KBr)
: 2129 cmꢁ1. LRMS (EI) m/z: 418 (Mþ,
100), 297 (68), 212 (96), 206 (91). HRMS: m/z [M]þ calcd for
23H21Sb: 418.0681. Found: 418.0685.
4c (0.5 mmol), 5 (0.6 mmol), DMAP (0.5 mmol), Et3N (0.6 mmol).
Isolated yield.
b
d
3. Conclusion
n
The Cu-catalyzed azide-alkyne cycloaddition of various ethy-
nylstibanes with benzylazide, under mild reaction conditions,
afforded novel trisubstituted 5-organostibano-1H-1,2,3-triazoles.
Further, a method for the synthesis of fully substituted 5-acyl-1,2,3-
C
4.2.3. Phenylethynyl-di-p-tolylstibine (2c)7b
Colorless needle (3.32 g, 82% yield), mp 58e61 ꢀC (Et2O-MeOH).
Please cite this article in press as: Yamada M, et al., Synthesis of 5-organostibano-1H-1,2,3-triazoles by Cu-catalyzed azide-alkyne cycloaddition
and their application in the acyl-induced deantimonation for the preparation of fully substituted 5-acyl-1,2,3-triazoles, Tetrahedron (2017),
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6
M. Yamada et al. / Tetrahedron xxx (2017) 1e9
Scheme 3. Possible mechanism.
1H NMR (400 MHz, CDCl3)
d
: 7.61 (4H, d, J ¼ 7.8 Hz), 7.52e7.48 (2H,
4.2.8. 1-Cyclohexenylethynyldi-p-tolylstibane (2h)
m), 7.31e7.28 (3H, m), 7.16 (4H, d, J ¼ 7.8 Hz), 2.32 (6H, s). 13C NMR
Colorless needle (2.13 g, 52% yield), mp 55e57 ꢀC (from Et2O-
(100 MHz, CDCl3)
d
: 138.7 (s),135.5 (d),134.4 (s),132.0 (d),129.8 (d),
EtOH). 1H NMR (400 MHz, CDCl3)
d
: 7.55 (4H, d, J ¼ 7.8 Hz), 7.14 (4H,
d, J ¼ 7.8 Hz), 6.21 (1H, s), 2.32 (6H, s), 2.19e2.17 (2H, m), 2.14e2.11
(2H, m), 1.67e1.53 (4H, m). 13C NMR (100 MHz, CDCl3)
: 138.4 (s),
135.9 (d), 135.4 (d), 134.7 (s), 129.7 (d) 121.1 (s), 113.3 (s), 82.4 (s),
128.4 (d), 128.2 (d), 123.4 (s), 110.9 (s), 86.0 (s), 21.4 (q). FTIR (KBr) n:
2363 cmꢁ1. LRMS (EI) m/z: 405 ([MþH]þ, 75), 327 (10), 303 (45), 212
(100), 77 (20). HRMS: m/z [M]þ calcd for C22H19Sb: 404.0525.
Found: 404.0530.
d
29.3 (t), 25.6 (t), 22.2 (t), 21.4 (t), 21.3 (q). FTIR (KBr) n .
: 2129 cmꢁ1
MS (EI) m/z: 408 (Mþ, 32), 287 (76), 212 (77), 83 (100). HRMS: m/z
[M]þ calcd for C22H23Sb: 408.0838. Found: 408.0841.
4.2.4. 4-Bromophenylethynyldi-p-tolylstibane (2d)
Colorless needle (3.29 g, 68% yield), mp 121e123 ꢀC (from
CH2Cl2-EtOH). 1H NMR (400 MHz, CDCl3)
d
: 7.58 (4H, d, J ¼ 8.3 Hz),
7.42 (2H, d, J ¼ 8.8 Hz) 7.34 (2H, d, J ¼ 8.3 Hz), 7.16 (4H, d, J ¼ 7.3 Hz),
2.33 (6H, s). 13C NMR (100 MHz, CDCl3)
: 138.8 (s), 135.5 (d), 134.2
(s), 133.4 (d), 131.5 (d), 129.8 (d), 122.7 (s), 122.3 (s), 109.6 (s), 87.6
4.2.9. n-Butylethynyldi-p-tolylstibane (2i)
Colorless oil (1.96 g, 51% yield). 1H NMR (400 MHz, CDCl3)
d: 7.56
(4H, d, J ¼ 7.8 Hz), 7.14 (4H, d, J ¼ 7.8 Hz), 2.40 (2H, t, J ¼ 6.8 Hz), 2.33
d
(6H, s), 1.58e1.52 (2H, m), 1.50e1.39 (2H, m), 0.94 (3H, t, J ¼ 7.3 Hz).
13C NMR (100 MHz, CDCl3)
d: 138.4 (s), 135.3 (d), 134.8 (d), 130.1 (s),
(s), 21.4 (q). FTIR (KBr)
n
: 2135 cmꢁ1. LRMS (EI) m/z: 484
([MþHþ2]þ, 80), 282 (68), 212 (100), 182 (72). HRMS: m/z [M]þ
129.2 (s) 113.2 (s), 31.0 (t), 21.9 (t), 21.3 (q), 20.1 (t), 13.6 (q). FTIR
(neat) n
: 2150 cmꢁ1. LRMS (EI) m/z: 384 (Mþ, 76), 212 (100), 182
calcd for C22H18BrSb: 481.9630. Found: 481.9627.
(78), 91 (65). HRMS: m/z [M]þ calcd for C20H23Sb: 384.0838. Found:
384.0834.
4.2.5. (4-Trifluoromethylphenylethynyl)(di-p-tolyl)stibane (2e)
Colorless needle (3.12 g, 66% yield), mp 72e74 ꢀC (from Et2O-
4.2.10. (Trimethylsilylethynyl)(di-p-tolyl)stibane (2j)
EtOH). 1H NMR (400 MHz, CDCl3)
d: 7.60e7.55 (8H, m), 7.18 (4H, d,
Colorless needle (2.53 g, 63% yield), mp 87e89 ꢀC (from Et2O-
J ¼ 7.8 Hz), 2.34 (6H, s). 13C NMR (100 MHz, CDCl3)
d: 138.9 (s), 135.5
(d), 134.0 (s), 132.2 (d), 130.1 (s, JC,F ¼ 33 Hz), 129.9 (d), 127.1 (s),
EtOH). 1H NMR (400 MHz, CDCl3)
d
: 7.55 (4H, d, J ¼ 7.8 Hz), 7.15 (4H,
2
d, J ¼ 7.8 Hz), 2.33 (6H, s), 0.22 (9H, s). 13C NMR (100 MHz, CDCl3)
d:
125.2 (d, 3JC,F ¼ 4 Hz), 123.9 (s, 1JC,F ¼ 271 Hz), 109.1 (s), 89.5 (s), 21.4
138.6 (s), 135.4 (d), 134.3 (s), 129.7 (d), 119.8 (s) 104.6 (s), 21.3 (q),
(q). FTIR (KBr) n
: 2134 cmꢁ1. LRMS (EI) m/z: 472 (Mþ, 36), 241 (100),
0.02 (q). FTIR (KBr) n
: 2079 cmꢁ1. LRMS (EI) m/z: 400 (Mþ, 95), 249
212 (60), 182 (38). HRMS: m/z [M]þ calcd for C23H18F3Sb: 472.0399.
(62), 212 (100), 173 (96). HRMS: m/z [M]þ calcd for C19H23SbSi:
Found: 472.0403.
400.0607. Found: 400.0611.
4.2.6. 2-Thienylethynyldi-p-tolylstibane (2f)
4.3. Preparation of 5-stibanotriazoles (4)
Colorless needle (2.26 g, 55% yield), mp 75e77 ꢀC (from Et2O-
EtOH). 1H NMR (400 MHz, CDCl3)
d
: 7.58 (4H, d, J ¼ 8.3 Hz), 7.25 (1H,
CuBr (3.6 mg, 0.025 mmol,
5 mol%), ethynylstibane (2:
dd, J ¼ 3.4, 1.5 Hz), 7.23 (1H, dd, J ¼ 5.4, 1.5 Hz), 7.17 (4H, d,
0.5 mmol), and benzyl azide (3: 66.6 mg, 0.5 mmol) were dissolved
in THF (4 mL). The reaction mixture was stirred for at 60 ꢀC. The
reaction mixture was diluted with CH2Cl2 (10 mL) and water
(10 mL). The phases were separated and aqueous layer was
extracted with CH2Cl2 (30 mL x 2). The combined organic layer was
washed 5% aqueous ammonia and water, dried over MgSO4 and
concentrated under reduced pressure. The residue was purified by
silica gel chromatography (n-hexane/AcOEt).
J ¼ 7.3 Hz), 6.96 (1H, dd, J ¼ 5.4, 3.4 Hz), 2.33 (6H, s). 13C NMR
(100 MHz, CDCl3) d: 138.8 (s), 135.5 (d), 134.2 (s), 132.5 (d), 129.8 (d)
127.2 (d), 126.8 (d), 123.5 (s), 103.3 (s), 90.8 (s), 21.4 (q). FTIR (KBr) n:
2125 cmꢁ1. LRMS (EI) m/z: 410 (Mþ, 50), 257 (62), 212 (100), 198
(85). HRMS: m/z [M]þ calcd for C20H17SSb: 410.0089. Found:
410.0092.
4.2.7. 2-Pyridylethynyldi-p-tolylstibane (2g)
Colorless needle (2.36 g, 58% yield), mp 93e95 ꢀC (from Et2O-
4.3.1. 1-Benzyl-4-(4-methoxy)-5-(di-p-tolylstibano)-1H-1,2,3-
EtOH). 1H NMR (400 MHz, CDCl3)
d
8.56 (1H, d, J ¼ 4.4 Hz),
7.61e7.58 (5H, m), 7.45 (1H, d, J ¼ 7.3 Hz), 7.20e7.15 (5H, m), 2.32
(6H, s). 13C NMR (100 MHz, CDCl3)
: 149.9 (d), 143.1 (s), 138.8 (s),
136.0 (d), 135.6 (d) 133.8 (s), 129.8 (d), 127.4 (d), 122.9 (d), 109.6 (s),
87.2 (s), 21.3 (q). FTIR (KBr)
: 2312 cmꢁ1. LRMS (EI) m/z: 405 (Mþ,
100), 284 (85), 212 (89), 182 (88). HRMS: m/z [M]þ calcd for
21H18NSb: 405.0477. Found: 405.0471.
triazole (4a)
Colorless oil (261 mg, 92% yield). 1H NMR (400 MHz, CDCl3)
d:
d
7.35 (2H, d, J ¼ 8.7 Hz), 7.23e7.12 (7H, m), 6.98 (4H, d, J ¼ 8.7 Hz),
6.75 (2H, d, J ¼ 6.8 Hz), 6.71 (2H, d, J ¼ 8.2 Hz), 5.31 (2H, s), 3.73 (3H,
n
s), 2.28 (6H, s). 13C NMR (100 MHz, CDCl3)
d: 159.4 (s), 156.4 (s),
139.2 (s), 135.8 (d), 135.7 (s), 130.8 (s), 130.3 (d), 129.9 (d), 128.3 (d),
127.6 (d), 127.1 (d), 126.3 (s), 124.5 (s), 113.5 (s), 55.2 (q), 54.0 (t),
C
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and their application in the acyl-induced deantimonation for the preparation of fully substituted 5-acyl-1,2,3-triazoles, Tetrahedron (2017),
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M. Yamada et al. / Tetrahedron xxx (2017) 1e9
7
21.3 (q). LRMS (FAB) m/z: 568 ([MþH]þ, 5), 309 (15), 307 (10), 195
4.3.7. 1-Benzyl-4-(2-pyridyl) -5-(di-p-tolylstibano)-1H-1,2,3-
triazole (4g)
Colorless plate (173 mg, 64% yield), mp 166e169 ꢀC (from n-
hexane-CH2Cl2). 1H NMR (400 MHz, CDCl3)
: 8.25e8.23 (2H, m),
(10), 135 (80), 119 (100), 85 (85), 79 (20), 47 (15). HRMS: m/z [M]þ
calcd for C30H28N3OSb: 567.1271. Found: 567.1269.
d
7.69 (1H, td, J ¼ 7.3, 2.0 Hz), 7.24e7.11 (7H, m), 7.05e7.02 (1H, ddd,
4.3.2. 1-Benzyl-4-(4-tolyl)-5-(di-p-tolylstibano)-1H-1,2,3-triazole
(4b)
J ¼ 7.6, 4.9, 1.0 Hz), 6.98 (4H, d, J ¼ 7.8 Hz), 6.54 (2H, d, J ¼ 6.3 Hz),
5.13 (2H, s), 2.28 (6H, s). 13C NMR (100 MHz, CDCl3)
d: 154.2 (s),
Colorless plate (235 mg, 85% yield), mp 86e88 ꢀC (from n-
hexane-CH2Cl2). 1H NMR (400 MHz, CDCl3)
d: 7.35 (2H, d,
150.6 (s), 147.4 (d), 138.4 (s), 136.7 (d), 136.4 (s), 136.2 (s), 136.0 (d),
131.1 (s), 129.6 (d), 128.2 (d), 127.3 (d), 126.3 (d), 122.2 (d), 119.9 (d),
53.1 (t), 21.3 (q). LRMS (FAB) m/z: 539 ([MþH]þ, 20), 449 (76), 447
(100), 207 (32), 91 (77). HRMS: m/z [M]þ calcd for C28H25N4Sb:
538.1117. Found: 538.1121.
J ¼ 7.8 Hz), 7.19e7.13 (7H, m), 7.04e6.99 (6H, m), 6.74 (2H, d,
J ¼ 7.3 Hz), 5.30 (2H, s), 2.30 (9H, s). 13C NMR (100 MHz, CDCl3)
d:
156.7 (s), 139.2 (s), 137.6 (s), 135.8 (d), 135.7 (s), 130.8 (s), 129.9 (d),
129.1 (s), 128.9 (d), 128.7 (d), 128.3 (d), 127.6 (d), 127.1 (d), 126.5 (s),
53.9 (t), 21.3 (q), 21.2 (q). LRMS (FAB) m/z: 552 ([MþH]þ, 100), 220
(22), 91 (24). HRMS: m/z [M]þ calcd for C30H28N3Sb: 551.1321.
Found: 551.1325.
4.3.8. 1-Benzyl-4-(1-cyclohexenyl)-5-(di-p-tolylstibano)-1H-1,2,3-
triazole (4h)
Colorless plate (209 mg, 77% yield), mp 126e128 ꢀC (from n-
hexane-CH2Cl2). 1H NMR (400 MHz, CDCl3)
d: 7.25e7.16 (7H, m),
4.3.3. 1-Benzyl-4-phenyl-5-(di-p-tolylstibano)-1H-1,2,3-triazole
(4c)19
7.07 (4H, d, J ¼ 7.3 Hz), 6.72 (2H, d, J ¼ 6.8 Hz), 5.63e5.59 (1H, m),
5.23 (2H, s), 2.36e2.34 (2H, m), 2.32 (6H, s), 1.84e1.80 (2H, m),
Colorless plate (250 mg, 93% yield), mp 128e129 ꢀC (from n-
1.55e1.50 (2H, m), 1.37e1.31 (2H, m). 13C NMR (100 MHz, CDCl3)
d:
hexane-Et2O). 1H NMR (400 MHz, CDCl3)
d
: 7.47e7.45 (2H, m),
7.23e7.10 (10H, m), 7.01 (4H, d, J ¼ 8.3 Hz), 6.75 (2H, d, J ¼ 7.3 Hz),
5.32 (2H, s), 2.29 (6H, s). 13C NMR (100 MHz, CDCl3)
: 156.5 (s),
158.5 (s), 139.1 (s), 135.8 (d), 135.7 (s), 131.8 (s), 129.81 (d), 129.80
(s), 129.78 (d), 128.3 (d), 127.6 (d), 127.1 (d), 126.0 (s), 53.8 (t), 28.5
(t), 25.2 (t), 22.4 (t), 21.5 (t), 21.3 (q). LRMS (FAB) m/z: 542 ([MþH]þ,
95), 91 (100), 85 (65). HRMS: m/z [M]þ calcd for C29H30N3Sb:
541.1478. Found: 541.1471.
d
139.1 (s), 135.7 (d), 135.6 (s), 131.9 (s), 130.7 (s), 129.9 (d), 129.0 (d),
128.3 (d), 127.9 (d), 127.7 (d), 127.6 (d), 127.0 (d), 126.8 (s), 53.9 (t),
21.3 (q). LRMS (FAB) m/z: 538 ([MþH]þ, 40), 303 (12), 235 (25), 206
(100), 182 (82), 149 (50), 116 (70), 91 (40), 89 (25), 65 (20). HRMS:
m/z [M]þ calcd for C29H26N3Sb: 537.1165. Found: 537.1157.
4.3.9. 1-Benzyl-4-butyl-5-(di-p-tolylstibano)-1H-1,2,3-triazole (4i)
Colorless needle (226 mg, 87% yield), mp 73e74 ꢀC (from n-
hexane-CH2Cl2). 1H NMR (400 MHz, CDCl3)
d: 7.19e7.15 (7H, m),
4.3.4. 1-Benzyl-4-(4-bromophenyl)-5-(di-p-tolylstibano)-1H-1,2,3-
triazole (4d)
7.10 (4H, d, J ¼ 7.3 Hz), 6.93e6.91 (2H, m), 5.50 (2H, s), 2.33 (6H, s),
2.25 (2H, t, J ¼ 6.8 Hz), 1.29 (2H, sext, J ¼ 7.8 Hz), 1.01 (2H, quin,
Colorless plate (241 mg, 78% yield), mp 122e124 ꢀC (from n-
J ¼ 7.8 Hz), 0.70 (3H, t, J ¼ 7.3 Hz). 13C NMR (100 MHz, CDCl3)
d:
hexane-CH2Cl2). 1H NMR (400 MHz, CDCl3)
d: 7.25e7.17 (7H, m),
156.5 (s), 139.2 (s), 135.8 (d), 135.7(s), 130.2 (s), 129.9 (d), 128.5 (d),
127.8 (d), 127.2 (d), 126.3 (s), 54.2 (t), 32.3 (t), 26.3 (t), 22.5 (t), 21.3
(q), 13.6 (q). LRMS (FAB) m/z: 518 ([MþH]þ, 100), 119 (25), 91 (41),
85 (29). HRMS: m/z [M]þ calcd for C27H30N3Sb: 517.1478. Found:
517.1469.
7.09 (4H, d, J ¼ 7.8 Hz), 6.99 (4H, d, J ¼ 8.3 Hz), 6.83 (2H, d,
J ¼ 7.8 Hz), 5.40 (2H, s), 2.31 (6H, s). 13C NMR (100 MHz, CDCl3)
d:
155.2 (s), 139.4 (s), 135.7 (d), 135.3 (s), 130.83 (d), 130.80 (s), 130.5
(d), 130.4 (s), 130.0 (d), 128.5 (d), 127.9 (d), 127.3 (d), 126.9 (s), 121.9
(s), 54.2 (t), 21.3 (q). LRMS (FAB) m/z: 618 ([MþHþ2]þ, 100), 303
(22), 181 (15), 91 (57). HRMS: m/z [M]þ calcd for C29H25BrN3Sb:
615.0270. Found: 615.0264.
4.3.10. 1-Benzyl-4-trimethylsilyl-5-(di-p-tolylstibano)-1H-1,2,3-
triazole (4j)
Colorless plate (208 mg, 78% yield), mp 92e95 ꢀC (from n-
hexane-CH2Cl2). 1H NMR (400 MHz, CDCl3)
d
: 7.18 (4H, d, J ¼ 7.8 Hz),
7.14e7.04 (7H, m), 6.50 (2H, d, J ¼ 8.3 Hz), 5.18 (2H, s), 2.33 (6H, s),
0.40 (9H, s). 13C NMR (100 MHz, CDCl3)
: 155.9 (s), 139.3 (s), 135.8
4.3.5. 1-Benzyl-4-(4-trifluoromethylphenyl)-5-(di-p-tolylstibano)-
1H-1,2,3-triazole (4e)
Colorless needle (255 mg, 84% yield), mp 132e134 ꢀC (from n-
d
hexane-CH2Cl2). 1H NMR (400 MHz, CDCl3)
d: 7.39 (2H, d,
(s), 135.6 (d), 134.9 (s), 130.5 (s), 130.1 (d), 127.9 (d), 127.1 (d), 126.7
(d), 53.0 (t), 21.3 (q), 0.24 (q). LRMS (FAB) m/z: 536 (98), 534
([MþH]þ, 100), 91 (90), 73 (25). HRMS: m/z [M]þ calcd for
J ¼ 8.3 Hz), 7.30 (2H, d, J ¼ 8.3 Hz), 7.24e7.20 (3H, m), 7.09 (4H, d,
J ¼ 7.8 Hz), 6.98 (4H, d, J ¼ 7.3 Hz), 6.92 (2H, d, J ¼ 7.3 Hz), 5.45 (2H,
s), 2.28 (6H, s). 13C NMR (100 MHz, CDCl3)
d: 154.9 (s), 139.5 (s),
C26H30N3SbSi: 533.1247. Found: 533.1252.
135.7 (d), 135.4 (s), 135.3 (s), 130.4 (s), 130.0 (d), 129.4 (s,
2JC,F ¼ 28 Hz),129.2 (d),128.6 (d),128.1 (d),127.6 (s),127.5 (d), 124.5,
4.4. Preparation of triazolyl ketone (6e12, 14e17)
3
(d, JC,F ¼ 4.1 Hz), 124.1 (s, 1JC,F ¼ 272 Hz), 54.4 (t), 21.2 (q). LRMS
(FAB) m/z: 606 ([MþH]þ, 55), 303 (18), 181 (19), 91 (100). HRMS: m/
z [M]þ calcd for C30H25F3N3Sb: 605.1039. Found: 605.1042.
5-Stibanotriazole (4) (0.5 mmol), 4-dimethylaminopyridine
(61.1 mg, 0.5 mmol, 1 eq.), acyl chloride (5) (0.6 mmol, 1.2 eq.),
triethylamine (83.2 mL, 0.6 mmol, 1.2 eq.) were dissolved in 1,2-DCE
4.3.6. 1-Benzyl-4-(2-thienyl)-5-(di-p-tolylstibano)-1H-1,2,3-
triazole (4f)
(5 mL) and stirred at 80 ꢀC under argon. After 20 h, the reaction
mixture was diluted with CH2Cl2 (5 mL) and saturated NaHCO3
aqueous solution (5 mL). The phases were separated and aqueous
layer was extracted with CH2Cl2 (30 mL x 2). The combined organic
layers were washed saturated NaHCO3 aqueous solution (30 mL),
dried over MgSO4, and concentrated under reduced pressure. The
residue was purified by silica gel chromatography.
Colorless plate (172 mg, 63% yield), mp 128e130 ꢀC (from n-
hexane-CH2Cl2). 1H NMR (400 MHz, CDCl3)
d
: 7.21 (1H, dd, J ¼ 5.4,
1.4 Hz), 7.17e7.11 (7H, m), 7.06e7.02 (5H, m), 6.86 (1H, dd, J ¼ 5.4,
3.4 Hz), 6.69 (2H, dd, J ¼ 7.4, 1.4 Hz), 5.29 (2H, s), 2.30 (6H, s). 13
C
NMR (100 MHz, CDCl3) d: 150.5 (s), 139.3 (s), 135.8 (d), 135.7 (s),
133.8 (s), 130.7 (s), 130.1 (d), 128.3 (d), 127.6 (d), 127.1 (d), 126.94 (d),
126.87 (d), 126.86 (s), 125.8 (d), 53.9 (t), 21.3 (q). LRMS (FAB) m/z:
544 ([MþH]þ, 100), 303 (25), 212 (44), 91 (96). HRMS: m/z [M]þ
calcd for C27H24N3SSb: 543.0729. Found: 543.0735.
4.4.1. (1-Benzyl-4-phenyl-1H-1,2,3-triazol-5-yl)(phenyl)
methanone (6)23
Colorless needle (129 mg, 76% yield), mp 96e97 ꢀC (from n-
Please cite this article in press as: Yamada M, et al., Synthesis of 5-organostibano-1H-1,2,3-triazoles by Cu-catalyzed azide-alkyne cycloaddition
and their application in the acyl-induced deantimonation for the preparation of fully substituted 5-acyl-1,2,3-triazoles, Tetrahedron (2017),
http://dx.doi.org/10.1016/j.tet.2017.03.046

8
M. Yamada et al. / Tetrahedron xxx (2017) 1e9
hexane-AcOEt). 1H NMR (400 MHz, CDCl3)
d
: 7.50e7.48 (2H, m),
128.5 (d), 128.1 (d), 123.4 (d), 53.7 (t). FTIR (KBr) n
: 1666 cmꢁ1. LRMS
7.43e7.38 (3H, m), 7.25e7.15 (10H, m), 5.75 (2H, s). 13C NMR
(EI) m/z: 384 (Mþ, 90), 355 (30), 265 (40), 150 (45), 120 (45), 91
(100), 65 (36). HRMS: m/z [M]þ calcd for C22H16N4O3: 384.1222.
Found: 384.1230.
(100 MHz, CDCl3)
d
: 187.7 (s), 148.7 (s), 135.7 (s), 134.6 (s), 134.1 ꢂ 2
(d), 130.2 (s), 129.6 ꢂ 2 (s, d), 128.7 (d), 128.5 (d), 128.4 (d), 128.33
(d), 128.30 (d), 128.1 (d), 53.4 (t). FTIR (KBr) n
: 1655 cmꢁ1. LRMS (EI)
m/z:339 (Mþ, 98), 310 (18), 220 (31), 206 (28),178 (12), 165 (15),105
(75), 91 (100), 77 (66), 65 (47). HRMS: m/z [M]þ calcd for
4.4.7. (1-Benzyl-4-phenyl-1H-1,2,3-triazol-5-yl)(2-thienyl)
methanone (12)
Colorless plate (131 mg, 76% yield), mp 121e122 ꢀC (from n-
C
22H17N3O: 339.1372. Found: 339.1380.
hexane-AcOEt). 1H NMR (400 MHz, CDCl3)
d: 7.59 (1H, dd,
4.4.2. (1-Benzyl-4-phenyl-1H-1,2,3-triazol-5-yl)(4-methoxyphenyl)
methanone (7)
J ¼ 4.9 Hz, 1.0 Hz), 7.57e7.53 (2H, m), 7.30e7.16 (8H, m), 7.01 (1H,
dd, J ¼ 3.9 Hz, 1.0 Hz), 6.75 (1H, dd, J ¼ 4.9 Hz, 3.9 Hz), 5.71 (2H, s).
Colorless prism (85 mg, 46% yield), mp 84e86 ꢀC (from n-hex-
13C NMR (100 MHz, CDCl3)
d: 179.2 (s), 147.6 (s), 142.3 (s), 136.4 (d),
ane-AcOEt). 1H NMR (400 MHz, CDCl3)
d
: 7.52e7.45 (4H, m),
7.24e7.15 (8H, m), 6.66 (2H, d, J ¼ 8.8 Hz), 5.70 (2H, s), 3.76 (3H, s).
13C NMR (100 MHz, CDCl3)
: 186.1 (s), 164.4 (s), 147.7 (s), 134.6 (s),
136.1 (d), 134.4 (s), 130.3 (s), 129.6 (s), 128.7 (d), 128.6 (d), 128.5 (d),
128.4 (d), 128.3 (d), 128.2 (d), 128.1 (d), 53.2 (t). FTIR (KBr) n:
1630 cmꢁ1. LRMS (EI) m/z: 345 (Mþ, 20), 149 (10), 111 (20), 91 (100).
HRMS: m/z [M]þ calcd for C20H15N3OS: 345.0936. Found: 345.0942.
d
132.2 (d), 130.6 (s), 129.7 (s), 128.7 ꢂ 2 (d, s), 128.41 (d), 128.38 (d),
128.36 (d), 128.2 (d), 128.1 (d), 113.8 (d), 55.5 (q), 53.2 (t). FTIR (KBr)
n
: 1641 cmꢁ1. LRMS (EI) m/z: 369 (Mþ, 25), 343 (70), 152 (50), 135
4.4.8. [1-Benzyl-4-(4-methoxyphenyl)-1H-1,2,3-triazol-5-
yl](phenyl)methanone (14)23
(86), 91 (100), 83 (46), 61 (47). HRMS: m/z [M]þ calcd for
23H19N3O2: 369.1477. Found: 369.1468.
C
Yellow plate (139 mg, 75% yield), mp 81e82 ꢀC (from n-hexane-
AcOEt). 1H NMR (400 MHz, CDCl3)
d
: 7.50 (2H, dd, J ¼ 1.2, 8.8 Hz),
4.4.3. (1-Benzyl-4-phenyl-1H-1,2,3-triazol-5-yl)(p-tolyl)
methanone (8)23
7.41 (1H, t, J ¼ 7.6 Hz), 7.34 (2H, d, J ¼ 8.8 Hz), 7.25e7.15 (7H, m),
6.69 (2H, d, J ¼ 8.8 Hz), 5.74 (2H, s), 3.72 (3H, s). 13C NMR (100 MHz,
Colorless plate (113 mg, 64% yield), mp 57e58 ꢀC (from n-hex-
CDCl3) d: 187.8 (s), 159.7 (s), 148.5 (s), 135.8 (s), 134.8 (s), 134.0 (d),
ane-EtOH). 1H NMR (400 MHz, CDCl3)
d
: 7.48e7.42 (2H, m), 7.41
(2H, d, J ¼ 7.8 Hz), 7.23e7.14 (8H, m), 6.98 (2H, d, J ¼ 7.8 Hz), 5.71
(2H, s), 2.27 (3H, s). 13C NMR (100 MHz, CDCl3)
: 187.4 (s), 148.1 (s),
129.7 (d), 129.64 (s), 129.58 (d), 128.7 (d), 128.5 (d), 128.4 (d), 128.1
(d), 122.1 (s), 113.8 (d), 55.2 (q), 53.4 (t). FTIR (KBr) n .
: 1647 cmꢁ1
d
LRMS (EI) m/z: 369 (Mþ, 95), 105 (100), 91 (75), 65 (40). HRMS: m/z
145.4 (s), 134.6 (s), 133.2 (s), 130.5 (s), 129.8 (d), 129.7 (s), 129.2 (d),
128.7 (d), 128.38 (d), 128.37 (d), 128.3 (d), 128.2 (d), 128.1 (d), 53.3
[M]þ calcd for C23H19N3O2: 369.1477. Found: 369.1469.
(t), 21.7 (q). FTIR (KBr) n
: 1657 cmꢁ1. LRMS (EI) m/z: 353 (Mþ, 42),
4.4.9. [1-Benzyl-4-(p-tolyl)-1H-1,2,3-triazol-5-yl](phenyl)
149 (25), 119 (65), 91 (100), 83 (95), 65 (17). HRMS: m/z [M]þ calcd
methanone (15)23
for C23H19N3O: 353.1528. Found: 353.1530.
Yellow oil (113 mg, 64% yield). 1H NMR (400 MHz, CDCl3)
d: 7.53
(2H, d, J ¼ 7.8 Hz), 7.41 (1H, t, J ¼ 7.8 Hz), 7.30 (2H, d, J ¼ 8.3 Hz),
4.4.4. (1-Benzyl-4-phenyl-1H-1,2,3-triazol-5-yl)(4-bromophenyl)
methanone (9)23
7.24e7.14 (7H, m), 6.97 (2H, d, J ¼ 8.3 Hz), 5.73 (2H, s), 2.24 (3H, s).
13C NMR (100 MHz, CDCl3)
d: 187.9 (s), 148.6 (s), 138.4 (s), 135.7 (s),
Colorless prism (151 mg, 72% yield), mp 152e153 ꢀC (from n-
134.7 (s), 134.0 (d), 130.0 (s), 129.6 (d), 129.0 (d), 128.7 (d), 128.43
(d), 128.38 (d), 128.2 (d), 128.1 (d), 126.7 (s), 53.3 (t), 21.2 (q). FTIR
hexane-CH2Cl2). 1H NMR (400 MHz, CDCl3)
d
: 7.40e7.38 (2H, m),
7.34e7.29 (4H, m), 7.23e7.17 (8H, m), 5.75 (2H, s). 13C NMR
(100 MHz, CDCl3) : 186.6 (s), 148.7 (s), 134.5 (s), 134.4 (s), 131.8 (d),
130.9 (d), 129.8 (s), 129.5 (s), 129.4 (s), 128.8 (d), 128.52 (d), 128.47
(neat) n
: 1645 cmꢁ1. LRMS (EI) m/z: 353 (Mþ, 95), 324 (20), 279 (70),
d
234 (45), 167 (75), 149 (90), 105 (85), 91 (100), 77 (65), 57 (50).
HRMS: m/z [M]þ calcd for C23H19N3O: 353.1528. Found: 353.1533.
(d), 128.3 (d), 128.1 (d),53.4 (t). FTIR (KBr) n
: 1661 cmꢁ1. LRMS (EI)
m/z: 419([Mþ2]þ, 28), 417 (Mþ, 28), 183 (30), 91 (100), 65 (12).
HRMS: m/z [M]þ calcd for C22H16BrN3O: 417.0477. Found: 417.0460.
4.4.10. {1-Benzyl-4-[4-(trifluoromethyl)phenyl]-1H-1,2,3-triazol-5-
yl}(phenyl)methanone (16)
Yellow oil (112 mg, 55% yield). 1H NMR (400 MHz, CDCl3)
d
: 7.55
4.4.5. (1-Benzyl-4-phenyl-1H-1,2,3-triazol-5-yl)[4-
(trifluoromethyl)phenyl]methanone (10)
(2H, d, J ¼ 8.2 Hz), 7.50e7.41 (5H, m), 7.25e7.16 (7H, m), 5.74 (2H, s).
13C NMR (100 MHz, CDCl3)
d: 187.4 (s), 146.9 (s), 135.5 (s), 134.5 (d),
Colorless prism (161 mg, 79% yield), mp 79e80 ꢀC (from n-
134.3 (s), 133.1 (s), 131.0 (s), 130.3 (s, 2JC,F ¼ 33.1 Hz), 129.5 (d), 128.8
hexane-CH2Cl2). 1H NMR (400 MHz, CDCl3)
d
:
7.54 (2H, d,
J ¼ 8.3 Hz), 7.40 (2H, d, J ¼ 8.3 Hz), 7.34 (2H, dd, J ¼ 7.8 Hz, 2.0 Hz),
7.26e7.13 (8H, m), 5.80 (2H, s). 13C NMR (100 MHz, CDCl3)
: 186.5
(d), 128.7 (d), 128.6 (d), 128.3 (d), 128.2 (d), 125.3 (d, 3JC,F ¼ 3.7 Hz),
123.8 (s, 1JC,F ¼ 272.3 Hz), 53.5 (t). FTIR (neat)
n
: 1655 cmꢁ1. LRMS
d
(EI) m/z: 407 (Mþ, 25), 379 (70), 378 (15), 274 (20), 105 (70), 91
(100), 77 (40), 65 (20). HRMS: m/z [M]þ calcd for C23H16F3N3O:
407.1245. Found: 407.1250.
(s), 149.4 (s), 138.4 (s), 135.1 (s), 134.7 (s), 134.5 (s), 129.7 (d), 129.5
(s, 2JC,F ¼ 37.2 Hz), 128.9 (d), 128.8 (d), 128.6 (d), 128.5 (d), 128.4 (d),
128.1 (d), 125.3 (d, 3JC,F ¼ 3.3 Hz), 123.1 (s, 1JC,F ¼ 272.3 Hz), 53.6 (t).
FTIR (KBr) n
: 1668 cmꢁ1. LRMS (EI) m/z: 407 (Mþ, 64), 378 (16), 288
(25), 173 (62), 145 (50), 91 (100), 65 (21). HRMS: m/z [M]þ calcd for
23H16F3N3O: 407.1245. Found: 407.1238.
4.4.11. (1-Benzyl-4-butyl-1H-1,2,3-triazol-5-yl)(phenyl)methanone
C
(17)23
Colorless oil (121 mg, 76% yield). 1H NMR (400 MHz, CDCl3)
d:
4.4.6. (1-Benzyl-4-phenyl-1H-1,2,3-triazol-5-yl)(4-nitrophenyl)
methanone (11)23
7.64e7.54 (3H, m), 7.44 (2H, t, J ¼ 7.3 Hz), 7.26e7.16 (5H, m), 5.74
(2H, s), 2.42 (2H, t, J ¼ 7.8 Hz), 1.50 (2H, quin, J ¼ 7.8 Hz), 1.13 (2H,
Yellow plate (148 mg, 77% yield), mp 121e122 ꢀC (from MeOH-
sext, J ¼ 7.3 Hz), 0.73 (3H, t, J ¼ 7.3 Hz). 13C NMR (100 MHz, CDCl3)
d:
AcOEt). 1H NMR (400 MHz, CDCl3)
d
: 8.30 (1H, d, J ¼ 8.8 Hz), 8.24
187.4 (s), 150.3 (s), 137.2 (s), 135.1 (s), 133.9 (d), 130.9 (s), 129.1 (d),
128.8 (d), 128.7 (d), 128.3 (d), 128.0 (d), 53.3 (t), 31.4 (t), 25.8 (t),
(1H, d, J ¼ 8.8 Hz), 7.96 (2H, d, J ¼ 8.1 Hz), 7.33 (2H, d, J ¼ 7.6 Hz),
7.26e7.10 (6H, m), 7.57 (2H, d, J ¼ 8.1 Hz), 5.75 (2H, s). 13C NMR
22.2 (t), 13.5 (q). FTIR (neat)
75), 105 (80), 91 (100), 65 (30). HRMS: m/z [M]þ calcd for
20H21N3O: 319.1685. Found: 319.1679.
n
: 1655 cmꢁ1. LRMS (EI) m/z: 319 (Mþ,
(100 MHz, CDCl3) d: 185.7 (s), 150.3 (s), 149.8 (s) 140.2 (s), 134.5 (s),
130.3 (d), 129.3 (s), 129.1 (d), 129.0 (s), 128.9 (d), 128.7 (d), 128.6 (d),
C
Please cite this article in press as: Yamada M, et al., Synthesis of 5-organostibano-1H-1,2,3-triazoles by Cu-catalyzed azide-alkyne cycloaddition
and their application in the acyl-induced deantimonation for the preparation of fully substituted 5-acyl-1,2,3-triazoles, Tetrahedron (2017),
http://dx.doi.org/10.1016/j.tet.2017.03.046

M. Yamada et al. / Tetrahedron xxx (2017) 1e9
4959e4966;
9
4.5. Single crystal X-ray diffraction experiment data of 4g
(c) Yasuike S, Kawara S, Okajima S, Seki H, Yamaguchi K, Kurita J. Tetrahedron
Lett. 2004;45:9135e9138.
7. (a) Kakusawa N, Yamaguchi K, Kurita J, Tsuchita T. Tetrahedron Lett. 2000;41:
4143e4146;
(b) Kakusawa N, Yamaguchi K, Kurita J.
2956e2966;
(c) Kakusawa N, Kurita J. Chem Pharm Bull. 2005;53:1369e1371;
(d) Kakusawa N, Kurita J. Chem Pharm Bull. 2006;54:699e702;
(e) Kakusawa N, Tobiyasu Y, Yasuike S, Yamaguchi K, Seki H, Kurita J. Tetra-
hedron Lett. 2003;44:8589e8592;
(f) Kakusawa N, Tobiyasu Y, Yasuike S, Yamaguchi K, Seki H, Kurita J.
J Organomet Chem. 2006;691:2953e2968;
(g) Kakusawa N, Kurita J. Hetelocycles. 2006;68:1335e1348.
8. (a) Kakusawa N, Ikeda T, Osada A, Kurita J, Tsuchiya T. Synlett. 2000:
1503e1505;
(b) Okajima S, Yasuike S, Kakusawa N, et al. J Organomet Chem. 2002;656:
234e242;
The colourless prismatic crystal (0.060 ꢂ 0.060 ꢂ 0.020 mm3),
which was obtained from dichloromethane/n-hexane, was
immersed in Paraton-N oil and placed in the N2 cold stream at
100 K. The diffraction experiment was performed in a Bruker
J Organomet Chem. 2005;690:
D8VENTURE system (PHOTON-100 CMOS detector, CuKa:
l
¼ 1.54178 Å). Absorption correction was performed by an
empirical method implemented in SADABS.28 Structure solution
and refinement were performed by using SHELXT-2014/529 and
SHELXL-2016/430
.
C
28H25N4Sb, Mr ¼ 539.27; triclinic, space group P-1, Z ¼ 2,
Dcalc ¼ 1.463 g cmꢁ3, a ¼ 9.1666(7), b ¼ 10.1360(8), c ¼ 14.1366(11)
Å,
a
¼ 108.389(3),
b
¼ 98.152(3),
g
¼ 94.042(3)ꢀ, V ¼ 1224.49(17) Å3,
(c) Yasuike S, Kishi Y, Kawara S, Yamaguchi K, Kurita J. J Organomet Chem.
2006;691:2213e2220.
9. (a) Fujiwara Y, Mitani M, Yasuike S, Kurita J, Kaji T. J Health Sci. 2005;51:
333e340;
15731 observed and 4422 independent [I > 2s(I)] reflections, 300
parameters, final R1 ¼ 0.0408, wR2 ¼ 0.0940, S ¼ 1.071 [I > 2
s(I)].
CCDC 1527951.
(b) Kohri K, Yoshida E, Yasuike S, Fujie T, Yamamoto C, Kaji T. J Toxicol Sci.
2015;40:321e327;
(c) Murakami M, Fujie T, Matsumura M, et al. Fundam Toxicol Sci. 2015;2:
61e66.
All non-hydrogen atoms were refined anisotropically. Hydrogen
atoms were refined isotropically on the calculated positions using a
riding model (AFIX 137, 23 and 43) with Uiso values constrained to
1.2 or 1.5 Ueq of their parent atoms.
10. (a) Wu P, Fokin VV. Aldrichim Acta. 2007;40:7e17;
(b) Moses JE, Moorhouse AD. Chem Soc Rev. 2007;36:1249e1262;
(c) Meldal M, Tornøe CW. Chem Rev. 2008;108:2952e3015;
(d) Hein JE, Fokin VV. Chem Soc Rev. 2010;39:1302e1315;
Acknowledgments
~
(e) Aragao-Leoneti V, Campo VL, Gomes AS, Field RA, Carvalho I. Tetrahedron.
2010;66:9475e9492;
This research was supported by a research grant from Nagai
Memorial Research Scholarship from the Pharmaceutical Society of
Japan. The authors also thank Institute of Pharmaceutical Life Sci-
ences, Aichi Gakuin University, and Hokuriku University for
generous financial support.
(f) Ackermann L, Potukuchi HK. Org Biomol Chem. 2010;8:4503e4513;
(g) Majumdar KC, Ray K. Synthesis. 2011:3767e3783;
(h) Berg R, Straub BF. Beilstein J Org Chem. 2013;9:2715e2750;
(i) Sokolova NV, Nenajdenko VG. RSC Adv. 2013;3:16212e16242;
ꢁ
ꢁ
(j) Haldon E, Nicasio MC, Perez PJ. Org Biomol Chem. 2015;13:9528e9550;
(k) Singh MS, Chowdhury S, Koley S. Tetrahedron. 2016;72:5257e5283.
11. (a) Thirumurugan P, Matosiuk D, Jozwiak K. Chem Rev. 2013;113:4905e4979;
(b) Debets MF, Berkel SSV, Dommerholt J, Dirks AJ, Rutjes FPJT, Delft FLV. Acc
Chem Res. 2011;44:805e815;
Appendix A. Supplementary data
(c) Agalave SG, Maujan SR, Pore VS. Chem Asian J. 2011;6:2696e2718;
(d) Mamidyala SK, Finn MG. Chem Soc Rev. 2010;39:1252e1261;
(e) Jewett JC, Bertozzi CR. Chem Soc Rev. 2010;39:1272e1279.
12. (a) Golas PL, Matyjaszewski K. Chem Soc Rev. 2010;39:1338e1354;
(b) Qin A, Lam JWY, Tang BZ. Chem Soc Rev. 2010;39:2522e2544;
(c) Bryant JJ, Bunz UH. Chem Asian J. 2013;8:1354e1367.
Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.tet.2017.03.046.
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Please cite this article in press as: Yamada M, et al., Synthesis of 5-organostibano-1H-1,2,3-triazoles by Cu-catalyzed azide-alkyne cycloaddition
and their application in the acyl-induced deantimonation for the preparation of fully substituted 5-acyl-1,2,3-triazoles, Tetrahedron (2017),
http://dx.doi.org/10.1016/j.tet.2017.03.046