Antimony–lithium exchange reaction: Synthesis of 1,4,5-trisubstituted-1,2,3-triazoles by triazolyllithium with electrophiles

Article abstract of DOI:10.1016/j.jorganchem.2017.02.019

Trisubstituted 5-stibano-1H-1,2,3-triazoles 3 was synthesized by the Cu-catalyzed [3 + 2] cycloaddition of ethynylstibane 1 with benzyl azide 2 in the presence of CuBr (5 mol%) under aerobic conditions. 5-Stibanotriazole 3 was treated with an equimolecular amount of phenyllithium (PhLi) in anhydrous THF under argon atmosphere at ?78 °C. Subsequent treatment with various electrophiles formed 1,4,5-trisubstituted-1,2,3-triazoles 5 containing a benzyl moiety. This reaction is a novel example of an antimony (Sb) – lithium (Li) exchange reaction for the functionalization of heterocycles.

Full text of DOI:10.1016/j.jorganchem.2017.02.019

Accepted Manuscript
Antimony–lithium exchange reaction: Synthesis of 1,4,5-trisubstituted-1,2,3-triazoles
by triazolyllithium with electrophiles
Mizuki Yamada, Mio Matsumura, Masatoshi Kawahata, Yuki Murata, Naoki
Kakusawa, Kentaro Yamaguchi, Shuji Yasuike
PII:
S0022-328X(17)30090-6
10.1016/j.jorganchem.2017.02.019
JOM 19808
DOI:
Reference:
To appear in: Journal of Organometallic Chemistry
Received Date: 28 November 2016
Revised Date: 5 February 2017
Accepted Date: 12 February 2017
Please cite this article as: M. Yamada, M. Matsumura, M. Kawahata, Y. Murata, N. Kakusawa, K.
Yamaguchi, S. Yasuike, Antimony–lithium exchange reaction: Synthesis of 1,4,5-trisubstituted-1,2,3-
triazoles by triazolyllithium with electrophiles, Journal of Organometallic Chemistry (2017), doi: 10.1016/
j.jorganchem.2017.02.019.
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Graphical Abstract:

ACCEPTED MANUSCRIPT
Note
Antimony–lithium exchange reaction: synthesis of 1,4,5-trisubstituted-1,2,3-triazoles by
triazolyllithium with electrophiles
Mizuki Yamada,a Mio Matsumura,a Masatoshi Kawahata,b Yuki Murata,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
*Corresponding authors.
Address: School of Pharmaceutical Sciences, Aichi Gakuin University, 1-100 Kusumoto-cho,
Chikusa-ku, Nagoya 464-8650, Japan
Tel: +81-52-757-6774
E-mail address: s-yasuik@dpc.agu.ac.jp (S. Yasuike)
1

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ABSTRACT
Trisubstituted 5-stibano-1H-1,2,3-triazoles 3 was synthesized by the Cu-catalyzed [3+2]
cycloaddition of ethynylstibane 1 with benzyl azide 2 in the presence of CuBr (5 mol%) under
aerobic conditions. 5-Stibanotriazole 3 was treated with an equimolecular amount of phenyllithium
(PhLi) in anhydrous THF under argon atmosphere at -78 °C. Subsequent treatment with various
electrophiles formed 1,4,5-trisubstituted-1,2,3-triazoles 5 containing a benzyl moiety. This reaction is
a novel example of an antimony (Sb) – lithium (Li) exchange reaction for the functionalization of
heterocycles.
Keywords:
Antimony–lithium exchange reaction
5-Stibano-1,2,3-triazole
1,4,5-Trisubstituted-1,2,3-triazole
Phenyllithium
Cu-catalyzed azide-alkyne cycloaddition
Highlights:
5-Stibano-1,2,3-triazole was prepared by the regioselective CuAAC of ethynylstibane with benzyl
azide.
Fully substituted 1,2,3-triazoles were prepared by the reaction of electrophiles with triazolyllithium.
This reaction is a novel example of an Sb-Li exchange reaction for the functionalization of
heterocycles.
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1. Introduction
1,2,3-Triazoles are important heterocycles, serving as key functional groups in many bioactive
molecules and pharmaceuticals [1, 2]. Among these, 1,4,5-trisubstituted-1,2,3-triazoles have attracted
interest as target molecules because of their use as reagents with biological activities. For instance,
SST0287CL1 I [3] exhibits heat shock protein 90 inhibition, sulfur-containing triazole II [4] is a
potential herbicide with antifungal activity, triazole III [5] behaves as a potent inhibitor of human
aromatase, and triazole derivative having isoxazolyl IV [6] is a potent non-pseudo-substrate inhibitor
of O6-alkylguanine-DNA-methyltransferase (Fig. 1). Consequently, a general method for the
synthesis of fully substituted 1,2,3-triazoles would be a valuable addition to existing synthetic
strategies [7]. 1,4,5-Trisubstituted-1,2,3-triazoles have been synthesized via functionalization of
1,2,3-triazoles by exploiting the reactivity of substrates that possess heavier main-group elements
such as Bi and Te at the C5-position. Fokin et al. reported the reaction of
5-bismuthano-1,2,3-triazoles with electrophiles such as acyl chlorides, diphosgene, sulfuryl chloride,
and halogens to form the corresponding fully substituted 1,2,3-triazoles [8]. Stefani et al. have
developed a derivatization protocol that exploits Sonogashira- and Suzuki-type cross-coupling
reactions of 5-tellanyl-1,2,3-triazoles [9, 10]. In addition, they reported the Te-Li exchange reaction
and
functionalization
of
5-(n-butyltellanyl)-1,4-diphenyl-1,2,3-triazole
to
afford
1,4,5-trisubstituted-1,2,3-triazoles [10]. Metal-lithium exchange reactions that generate
organolithium compounds are very important strategies in organic synthesis, and it is well known
that organometallic compounds containing heavier main-group elements such as Sn and Te are
excellent precursors for metal-lithium exchange reactions [11-13]. Heteroatom-Li exchange reactions
of group 15 elements such as Sb and Bi have been known for over 60 years [14-17]. However, their
reactivities and synthetic efficiencies remain underexplored. Recently, Yamago et al. reported Sb-
and Bi-metal exchange reactions of organoantimony and bismuth compounds, respectively, with
organolithium, and their application to the synthesis of a functionalized polymer [18]. On the other
hand, we recently reported the synthesis of 5-stibano-1,2,3-triazoles such as
1-benzyl-5-(di-p-tolylstibano)-4-phenyl-1,2,3-triazole by regioselective Cu-catalyzed azide-alkyne
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cycloaddition (CuAAC) of alkynylstibane with organic azides [19]. As a continuation of our studies
on 1,2,3-triazoles containing an antimony group, we now report the synthesis of fully substituted
1,2,3-triazoles having benzyl moiety by the reaction of electrophiles with the key lithium
intermediate 4 formed following an Sb-Li exchange reaction. This reaction constitutes a novel
examples of an Sb-Li exchange reaction for the functionalization of heterocycle, and the reaction
proceeds without impairing the benzyl position of the substrate.
Fig 1
2. Results and discussion
2.1 Synthesis and molecular structure of 1-benzyl-5-(diphenylstibano)-4-phenyl-1,2,3-triazole
Novel starting material 3 was prepared in 80% yield by the regioselective CuAAC of ethynylstibane
1 with benzyl azide 2. The reaction proceeded in the presence of CuBr (5 mol%) at 60 °C under
aerobic conditions, following a similar procedure previously reported by us (Scheme 1) [19]. The
13
molecular structure of compound 3 was confirmed by their spectral techniques (1H and C NMR,
MS). The regiochemistry of 5-stibanotriazole 3 was confirmed by single-crystal X-ray analysis (Fig.
2). Table 1 shows the selected bond lengths and angles. The central antimony atom exhibited trigonal
pyramidal structure with Sb–C bond lengths ranging 2.148 Å and C–Sb–C angles between 96.07°
and 99.13°. These bond lengths and angles were similar to Ph3Sb (2.143-2.169 Å, 96.0-98.0°) [20].
The bond lengths and angles of the triazole ring also showed values similar to
1-benzyl-4-phenyl-1,2,3-triazole [21]. Moreover, the crystal structure revealed intramolecular π-π
interaction. One phenyl ring on antimony atom and benzyl group adopt a parallel-displaced structure,
with distances of 3.755 Å between the centroids of the two phenyl rings (Ph1-Ph2).
Scheme 1
Fig 2
Table 1
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2.2 Antimony–lithium exchange reaction followed by trapping with electrophile
First, the optimal experimental conditions for the Sb-Li exchange reaction of 3 with organolithium
reagents such as n-BuLi, sec-BuLi, MeLi, lithium diisopropylamide (LDA), lithium
2,2,6,6-tetramethylpiperidide (LiTMP), and PhLi were determined. The generation of lithium
intermediate 4 was confirmed by the isolation of product 5a upon quenching the reaction with
iodomethane. The results including reaction conditions are summarized in Table 2. Several available
organolithium reagents were screened at -78 °C in THF (entries 1-6). In terms of yield, PhLi was
found to be the best reagent for this reaction, producing 86% of the expected product 5a, and
triphenylstibane as a by-product in 63% yield (entry 6). Other organolithium reagents were
inefficient and afforded complex mixtures. The reaction was found to be sensitive to reaction
temperature, with the reaction by PhLi at -20 °C and -40 °C giving inferior results. These reactions
also gave complex mixtures including compounds in which the benzyl position was methylated
(entries 7, 8). Thus, the optimum reaction conditions were determined to be as followed:
5-stibanotriazole 3 was treated with an equimolecular amount of PhLi in anhydrous THF under argon
atmosphere at -78 °C. Subsequent quenching with iodomethane resulted in the formation of product
5a.
Table 2
We next examined the scope of the functionalization of 5-stibano-1,2,3-triazole 3 via Sb-Li exchange
reactions, followed by trapping of the lithium intermediate with various electrophiles. The results are
summarized in Table 3. Compound 3 was treated with PhLi, and then trapped with aromatic
aldehydes to afford the corresponding alcohols 5b-e in good to excellent yields (entries 1-4). These
reactions were sensitive to the electronic nature of the aryl groups, with electron-donating groups
giving higher yields than that observed with electron-withdrawing groups. An alkyl aldehyde also
gave the corresponding product 5f in 73% yield (entry 5). Introduction of a heteroatom-containing
substituent group at the 5-position of 3 was achieved smoothly by using chlorotrimethylsilane,
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chlorotri-n-butyltin, and 1,2-diiodoethane as electrophiles (entries 6-8). It is known that benzylic
lithium intermediates can be easily generated, and that they can undergo chemical modification in the
presence of various electrophiles [22-24]. In the present reaction, the benzyl moiety in 3 and 5a-i
remained intact. Unfortunately, the reaction of intermediate 4 with acetophenone or
N,N-dimethylformamide gave a complex mixture under these conditions (entries 9, 10).
Table 3
At present, the mechanism of the Sb-Li exchange reaction is unclear. It is known that the reaction of
organometallic compounds containing heavier main-group elements with organolithium reagents
forms hypervalent ate complexes on the main-group atoms [25-29]. In previous work, we have
reported the nucleophilic displacement of the ethynyl groups on ethynylstibanes with organolithium
reagents [30-32]. The work showed that a more stable conjugated base is preferentially released in
the ligand exchange reaction. It is known that calculated pKa values of the C5-position of
1-methyl-1,2,3-triazole and benzene in DMSO are 27.8 [33] and 44.7 [34], respectively. In the
present case, the triazolyl group may be released from hypervalent ate complex A in preference to
the phenyl group based on PhLi to form triazolyllithium (Fig. 3). Indeed, this reaction gave
triphenylstibane 6 as a by-product. We probed the mechanism of this Sb-Li exchange reaction by
1
o
using H- and 121Sb-NMR spectroscopy at low temperature (-80 C). However, the proposed
intermediate species A and 4 could not be confirmed on the NMR time scale. These intermediates
might be unstable and/or exist equilibrium with each other.
Fig 3
3. Conclusion
In summary, we have demonstrated the synthesis of 1,4,5-trisubstituted-1,2,3-triazoles by the
reaction of electrophiles with the key lithium intermediate 4, formed following an Sb-Li exchange
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reaction. The obtained compounds 5b-h were first synthesis of trisubstituted 1,2,3-triazoles. Studies
on the synthetic application of this reaction and a detailed investigation of the reaction mechanisms
are in progress. Moreover, a screen for biological activity of the fully substituted 1,2,3-triazoles is
currently underway in our laboratory.
4. Experimental
4.1. General
Melting points were measured on a Yanagimoto micro melting point hot-stage apparatus (MP-S3)
1
and reported as uncorrected values. H NMR (TMS: δ: 0.00 or CH2Cl2: 5.30 ppm as an internal
standard) and 13C NMR (CDCl3: δ: 77.00 ppm as an internal standard) 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 µA). IR spectra were recorded on a Shimadzu
FTIR-8400S spectrophotometer and reported in terms of frequency of absorption (cm-1). 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 electrophiles were purchased
from Wako Pure Chemical Industries and Tokyo Chemical Industry Co., Ltd.
4.2. Synthesis of 1-benzyl-5-(diphenylstibano)-4-phenyl-1H-1,2,3-triazole (3)
CuBr (72 mg, 0.5 mmol, 5 mol%), (phenylethynyl)diphenylstibane (1 : 3.77 g, 10 mmol), and
benzyl azide (2 : 1.33 g, 10 mmol) were dissolved in THF (40 mL). The reaction mixture was stirred
for 6 h at 60 ºC. The reaction mixture was diluted with CH2Cl2 (30 mL) and water (30 mL). The
phases were separated and aqueous layer was extracted with CH2Cl2 (30 mL × 2). The combined
organic layers were 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 =
4 : 1), affording compound 3.
Colorless prisms (4.08 g, 80 % yield), mp: 105-107 ºC (from n-hexane-CH2Cl2). 1H NMR (400 MHz,
CDCl3) δ: 5.34 (2H, s), 6.78-6.81 (2H, m), 7.15-7.21 (10H, m), 7.24-7.28 (6H, m), 7.42-7.45 (2H, m).
13C NMR (100 MHz, CDCl3) δ: 54.1 (t), 126.6 (s), 127.2 (d), 127.8 (d), 127.9 (d), 128.0 (d), 128.5
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(d), 129.0 (d), 129.1 (d), 129.2 (d), 131.9 (s), 134.6 (s), 135.5 (s), 135.8 (d), 156.7 (s). LRMS (FAB)
m/z: 510 ([M+H]+, 100), 275 (22), 236 (15), 154 (17), 91 (53). HRMS: m/z [M]+ calcd for
C27H22N3Sb: 509.0852. Found: 509.0850.
4.3. General procedure for Sb/Li exchange followed by trapping with electrophile
PhLi (0.46 mL, 0.5 mmol, 1.54 mol/L in diethyl ether) was added to a solution of
1-benzyl-5-(diphenylstibano)-4-phenyl-1H-1,2,3-triazole (3 : 255 mg, 0.5 mmol) in THF (2 mL) at
-78 ºC. After 15 min, electrophile (0.75 mmol) was added and stirred at -78 ºC. Then the reaction
mixture was quenched with MeOH, diluted with CH2Cl2 (3 mL) and water (3 mL). The phases were
separated and organic layer was washed with brine (20 mL), dried over anhydrous MgSO4, and
concentrated under reduced pressure. The residue was purified by silica gel chromatography
(n-hexane : AcOEt) to give 5a-g, 5i (4 : 1), 5h (6 : 1).
4.3.1. 1-Benzyl-5-methyl-4-phenyl-1H-1,2,3-triazole (5a) [35]
1
Colorless plates (107 mg, 86% yield), mp 92-93 ºC (from n-hexane-CH2Cl2). H NMR (400 MHz,
CDCl3) δ: 2.33 (3H, s), 5.55 (2H, s), 7.20 (2H, d, J = 5.9 Hz), 7.29-7.38 (4H, m), 7.44 (2H, t, J = 7.6
Hz), 7.69 (2H, d, J = 7.3 Hz). 13C NMR (100 MHz, CDCl3) δ: 9.2 (q), 52.0 (t), 127.08 (d), 127.11 (d),
127.6 (d), 128.3 (d), 128.6 (d), 129.0 (d), 129.1 (s), 131.6 (s), 134.8 (s), 145.0 (s). LRMS (EI) m/z :
249 (M+, 100), 220 (16), 130 (100), 115 (15), 104 (62), 83 (80), 77 (23), 65 (20), 63 (15). HRMS:
m/z [M]+ calcd for C16H15N3: 249.1266. Found: 249.1252.
4.3.2. (1-Benzyl-4-phenyl-1H-1,2,3-triazol-5-yl)(4-methoxyphenyl)methanol (5b)
1
Colorless needles (158 mg, 85% yield), mp 165-168 ºC (from CH2Cl2). H NMR (400 MHz,
CDCl3) δ: 3.12 (1H, d, J = 4.9 Hz), 3.78 (3H, s), 5.30 (1H, d, J = 15.1 Hz), 5.46 (1H, d, J = 15.1 Hz),
6.27 (1H, d, J = 4.9 Hz), 6.76 (2H, d, J = 8.3 Hz), 7.02-7.10 (4H, m), 7.17-7.25 (3H, m), 7.32-7.39
13
(3H, m), 7.57 (2H, dd, J = 2.0, 7.8 Hz). C NMR (100 MHz, CDCl3) δ: 52.9 (t), 55.3 (q), 65.2 (d),
114.0 (d), 127.1 (d), 127.8 (d), 127.9 (d), 128.15 (d), 128.24 (d), 128.5 (d), 128.7 (d), 130.7 (s), 131.4
(s), 134.1 (s), 135.2 (s), 146.1 (s), 159.2 (s). FTIR (KBr) : 3188 cm-1. LRMS (EI) m/z : 371 (M+, 56),
355 (10), 236 (22), 207 (16), 149 (70), 130 (50), 91 (100), 77 (17), 65 (11). HRMS: m/z [M]+ calcd
for C23H21N3O2: 371.1634. Found: 371.1631.
4.3.3. (1-Benzyl-4-phenyl-1H-1,2,3-triazol-5-yl)(p-tolyl)methanol (5c)
1
Colorless needles (151 mg, 85% yield), mp 140-142 ºC (from n-hexane-CH2Cl2). H NMR (400
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MHz, CDCl3) δ: 2.31 (3H, s), 3.27 (1H, br), 5.25 (1H, d, J = 15.1 Hz), 5.43 (1H, d, J = 15.1 Hz),
6.29 (1H, s), 7.00-7.08 (6H, m), 7.15-7.23 (3H, m), 7.30-7.38 (3H, m), 7.55-7.60 (2H, m). 13C NMR
(100 MHz, CDCl3) δ: 21.0 (q), 52.8 (t), 65.3 (d), 125.7 (d), 127.9 (d), 128.1 (d), 128.2 (d), 128.5 (d),
128.7 (d), 129.3 (d), 130.7 (s), 134.1 (s), 135.1 (s), 136.4 (s), 137.7 (s), 146.1 (s). FTIR (KBr) : 3231
cm-1. LRMS (EI) m/z : 355 (M+, 92), 327 (12), 236 (61), 207 (23), 206 (15), 133 (70), 121 (22), 105
(21), 91 (100), 83 (22), 65 (15). HRMS: m/z [M]+ calcd for C23H21N3O: 355.1685. Found: 355.1689.
4.3.4. (1-Benzyl-4-phenyl-1H-1,2,3-triazol-5-yl)(4-bromophenyl)methanol (5d)
1
Colorless needles (147 mg, 70% yield), mp 152-153 ºC (from n-hexane-CH2Cl2). H NMR (400
MHz, CDCl3) δ: 4.31 (1H, br), 5.26 (1H, d, J = 15.2 Hz), 5.40 (1H, d, J = 15.2 Hz), 6.26 (1H, s),
6.90-6.98 (4H, m), 7.10-7.23 (3H, m), 7.23-7.26 (2H, m), 7.30-7.35 (3H, m), 7.45-7.52 (2H, m). 13C
NMR (100 MHz, CDCl3) δ: 52.9 (t), 64.7 (d), 121.8 (s), 127.5 (d), 127.7 (d), 127.9 (d), 128.1 (d),
128.4 (d), 128.5 (d), 128.7 (d), 130.3 (s), 131.5 (d), 133.8 (s), 134.7 (s), 138.5 (s), 146.1 (s). FTIR
(KBr) : 3211 cm-1. LRMS (EI) m/z : 419 (M+, 40), 300 (38), 221 (30), 197 (35), 185 (18), 178 (10),
116 (12), 91 (100), 77 (33), 65 (20). HRMS: m/z [M]+ calcd for C22H18BrN3O: 419.0633. Found:
419.0629.
4.3.5. (1-Benzyl-4-phenyl-1H-1,2,3-triazol-5-yl)[4-(trifluoromethyl)phenyl]methanol (5e)
1
Colorless needles (129 mg, 63% yield), mp 138-140 ºC (from n-hexane-CH2Cl2). H NMR (400
MHz, CDCl3) δ: 3.57 (1H, br), 5.34 (1H, d, J = 15.1 Hz), 5.45 (1H, d, J = 15.1 Hz), 6.36 (1H, s),
6.90 (2H, d, J = 7.3 Hz), 7.10-7.17 (3H, m), 7.21 (2H, d, J = 7.8 Hz), 7.36-7.40 (5H, m), 7.53-7.56
(2H, m). 13C NMR (100 MHz, CDCl3) δ: 52.9 (t), 64.6 (d), 123.9 (s), 125.2 (d), 126.1 (d), 127.5 (d),
128.0 (d), 128.1 (d), 128.4 (d), 128.5 (d), 128.8 (d), 129.9 (s), 130.1 (s), 133.8 (s), 134.5 (s), 143.3 (s),
146.2 (s). FTIR (KBr) : 3155 cm-1. LRMS (EI) m/z : 409 (M+, 28), 369 (10), 290 (60), 135 (15), 91
(100). HRMS: m/z [M]+ calcd for C23H18F3N3O: 409.1402. Found: 409.1411.
4.3.6. 1-(1-Benzyl-4-phenyl-1H-1,2,3-triazol-5-yl)-2-methylpropan-1-ol (5f)
1
Colorless plates (112 mg, 73% yield), mp 144.5-145.5 ºC (from n-hexane-CH2Cl2). H NMR (400
MHz, CDCl3) δ: 0.31 (3H, d, J = 6.9 Hz), 0.97 (3H, d, J = 6.9 Hz), 1.85-1.95 (1H, m), 3.47 (1H, br),
4.61 (1H, d, J = 9.6 Hz), 5.56 (1H, d, J = 15.5 Hz), 5.64 (1H, d, J = 15.5 Hz), 7.21 (2H, dd, J = 1.6,
7.9 Hz), 7.27-7.40 (6H, m), 7.64 (2H, dd, J = 1.6, 7.9 Hz). 13C NMR (100 MHz, CDCl3) δ: 18.7 (q),
19.5 (q), 32.8 (d), 52.8 (t), 70.6 (d), 127.3 (d), 128.05 (d), 128.13 (d), 128.5 (d), 128.7 (d), 128.8 (d),
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131.2 (s), 134.6 (s), 135.7 (s), 145.7 (s). FTIR (KBr) : 3204 cm-1. LRMS (EI) m/z : 307 (M+, 65), 188
(100), 129 (10), 104 (20), 91 (98), 83 (40), 65 (20). HRMS: m/z [M]+ calcd for C19H21N3O: 307.1685.
Found: 307.1679.
4.3.7. 1-Benzyl-4-phenyl-5-(trimethylsilyl)-1H-1,2,3-triazole (5g)
1
Colorless prisms (108 mg, 70% yield), mp 105-106 ºC (from n-hexane-CH2Cl2). H NMR (400
13
MHz, CDCl3) δ: 0.030 (9H, s), 5.75 (2H, s), 7.04 (2H, d, J = 6.8 Hz), 7.29-7.50 (8H, m). C NMR
(100 MHz, CDCl3) δ: -0.34 (q), 54.0 (t), 126.4 (d), 127.96 (d), 127.98 (d), 128.3 (d), 128.8 (d), 129.8
(d), 131.3 (s), 133.1 (s), 136.3 (s), 156.5 (s). LRMS (EI) m/z : 307 (M+, 65), 279 (98), 180 (20), 179
(11), 149 (16), 118 (11), 91 (100), 83 (92), 73 (45), 65 (24). HRMS: m/z [M]+ calcd for C18H21N3Si:
307.1505. Found: 307.1507.
4.3.8. 1-Benzyl-4-phenyl-5-(tributylstannyl)-1H-1,2,3-triazole (5h)
1
Colorless oil (194 mg, 74% yield). H NMR (400 MHz, CDCl3) δ: 0.73-0.84 (15H, m), 1.06-1.24
(12H, m), 5.67 (2H, s), 7.02 (2H, d, J = 6.6 Hz), 7.28-7.46 (6H, m), 7.52 (2H, dd, J = 1.6, 7.6 Hz).
13C NMR (100 MHz, CDCl3) δ : 10.8 (t), 13.5 (q), 27.0 (t), 28.6 (t), 54.3 (t), 126.3 (d), 128.01 (d),
128.03 (d), 128.2 (d), 128.8 (d), 132.0 (s), 133.3 (s), 136.6 (s), 157.1 (s). LRMS (FAB) m/z: 526
([M+H]+, 100), 524 (75), 468 (13), 466 (10), 179 (16), 177 (15), 119 (15), 91 (40), 85 (16). HRMS:
m/z [M]+ calcd for C27H39N3Sn: 525.2166. Found: 525.2161.
4.3.9. 1-Benzyl-5-iodo-4-phenyl-1H-1,2,3-triazole (5i) [36]
Colorless prisms (170 mg, 94% yield). mp 95-96 °C (from n-hexane-CH2Cl2). 1H NMR (400 MHz,
CDCl3) δ : 5.68 (2H, s), 7.30-7.48 (8H, m), 7.94 (2H, d, J = 7.3 Hz). 13C NMR (100 MHz, CDCl3) δ :
54.4 (t), 76.4 (s), 127.4 (d), 127.8 (d), 128.5 (d), 128.5 (d), 128.6 (d), 128.9 (d), 130.2 (s), 134.3 (s),
150.2 (s). LRMS (EI) m/z: 361 (M+, 13), 234 (22), 206 (95), 179 (27), 115 (11), 91 (100), 65 (14).
HRMS: m/z [M]+ calcd for C15H12IN3: 361.0076. Found: 361.0084.
4.4. X-Ray Crystallographic data
The X-ray diffraction measurements of compound 3 was carried out using Bruker D8 VENTURE
CCD area-detector diffractometer using CuKα radiation (λ = 1.54178 Å). The structure was solved
by SHELXT [37] followed by successive refinements using the full-matrix least-squares method on
F2 using SHELXL-2014 [38]. All the non-hydrogen atoms were refined anisotropically, whereas the
hydrogen atoms were refined isotropically.
10

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Crystal data of 3
C27H22N3Sb, M = 510.22, Monoclinic, a = 13.3913(14), b = 10.9832(12), c = 15.1619(17) Å, β =
99.913(3)°, V = 2196.7(4) Å3, Space group P21/n, Z = 4, Dcalc = 1.543 Mg/m3. Crystal size 0.20 x
0.20 x 0.02 mm3, θmax = 79.061°, 21970 reflections measured, 4515 unique (Rint = 0.0486), µ =
10.099 mm-1. The final R1 and wR2 were 0.0349 and 0.1014 (I > 2σ(I)), for 280 parameters. CCDC
1506003.
Acknowledgments
Partial financial support for this work was provided by a research grant from Institute of
Pharmaceutical Life Sciences, Aichi Gakuin University and Hokuriku University.
Supplementary data
Supplementary data related to this article can be found at http://
References and notes
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Fig. 2. ORTEP drawing of compound 3 with 50% probability. All hydrogen atoms are omitted for clarity.
Table 1. Selected bond lengths (Å) and bond angles (°) for 3.
Bond lengths
Sb–C1
Sb–C2
Sb–C3
C3–C4
C4–N1
N1–N2
N2–N3
N3–C3
2.148(4)
2.148(4)
2.148(4)
1.394(6)
1.364(5)
1.321(6)
1.331(5)
1.370(5)
Bond angles
C1–Sb–C2
C1–Sb–C3
C2–Sb–C3
C3–C4–N1
C4–N1–N2
N1–N2–N3
N2–N3–C3
N3–C3–C4
98.47(14)
99.13(15)
96.07(14)
109.4(4)
108.2(4)
107.8(3)
112.1(4)
102.5(3)

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Table 2. Antimony–lithium exchange reaction.a,b
Entry
RLi
Temp.
-78 °C
-78 °C
-78 °C
-78 °C
-78 °C
-78 °C
-40 °C
-20 °C
Lithiation (min)
Yield (%)
1
2
3
4
5
6
7
8
n-BuLi
sec-BuLi
MeLi
LDA
20
20
20
15
30
20
10
10
0
0
0
0
LiTMP
PhLi
0
86
12
0
PhLi
PhLi
a Reaction conditions: 3 (0.5 mmol), RLi (0.5 mmol), MeI (0.75 mmol).
b Isolated yield.

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Table 3. Synthesis of 1,4,5-trisubstituted-1,2,3-triazoles 5.a, b
Entry
1
Electrophile
Product
Yield (%)
5b: 85
2
5c: 85
5d: 70
5e: 63
5f: 73
5g: 70
5h: 74
5i: 94
Ph
Br
N
N
N
3
OH
Ph
4
5
6
7
I
8
I
9
5j:
0
10
5k:
0
a Reaction conditions: 3 (0.5 mmol), PhLi (0.5 mmol), Electrophile (0.75 mmol).
b Isolated yield.

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Li+
Ph
Ph
Ph
Ph
N
N
N
N
-
PhLi
N
N
Sb Ph
Ph
N
N
N
Li
Sb Ph
Ph
Ph3Sb
Ph
Ph
Ph
6
3
A
4
Fig. 3. Generation of triazolyllithium 4.

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Highlights:
5-Stibano-1,2,3-triazole was prepared by the regioselective CuAAC of ethynylstibane with benzyl
azide.
Fully substituted 1,2,3-triazoles were prepared by the reaction of electrophiles with triazolyllithium.
This reaction is a novel example of an Sb-Li exchange reaction for the functionalization of
heterocycles.