Rhodium(I)-Catalyzed Regioselective Azide-internal Alkynyl Trifluoromethyl Sulfide Cycloaddition and Azide-internal Thioalkyne Cycloaddition under Mild Conditions

Article abstract of DOI:10.1002/adsc.201801216

A regioselective method to access fully substituted 5-trifluoromethylthio-1,2,3-triazoles and 5-thio-1,2,3-triazoles from the internal alkynyl trifluoromethyl sulfides and internal thioalkynes by a rhodium(I)-catalyzed azide-alkyne cycloaddition (RhAAC) reaction under mild conditions has been developed. This approach features good compatibility with water and air, a broad substrate scope, good functional group tolerance, high yields and excellent regioselectivities. The high 1,5-regioselectivities were controlled by the strong coordination between the sulfur atom and the π-acidic rhodium. The advantages of this method further include its applicability to gram-scale preparation, the use of solid-phase synthesis technique, and the mutually orthogonal CuAAC-RhAAC reaction. (Figure presented.).

Full text of DOI:10.1002/adsc.201801216

Title: Rhodium(I)-Catalyzed Regioselective Azide-internal Alkynyl
Trifluoromethyl Sulfide Cycloaddition and Azide-internal
Thioalkyne Cycloaddition under Mild Conditions
Authors: Wangze Song, Nan Zheng, Ming Li, Junnan He, Junhao Li,
Kun Dong, Karim Ullah, and Yubin Zheng
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Adv. Synth. Catal. 10.1002/adsc.201801216
Link to VoR: http://dx.doi.org/10.1002/adsc.201801216

10.1002/adsc.201801216
Advanced Synthesis & Catalysis
COMMUNICATION
DOI: 10.1002/adsc.201((will be filled in by the editorial staff))
Rhodium(I)-Catalyzed Regioselective Azide-internal Alkynyl
Trifluoromethyl Sulfide Cycloaddition and Azide-internal
Thioalkyne Cycloaddition under Mild Conditions
Wangze Song,a,* Nan Zheng,a,b Ming Li,a Junnan He,b Junhao Li,a Kun Dong,a Karim
Ullah,a and Yubin Zhengb
a
State Key Laboratory of Fine Chemicals, School of Pharmaceutical Science and Technology, Dalian University of
Technology, Dalian, 116024, P. R. China.
E-mail: wzsong@dlut.edu.cn
State Key Laboratory of Fine Chemicals, School of Chemical Engineering, Dalian University of Technology, Dalian,
b
116024, P. R. China.
Received: ((will be filled in by the editorial staff))
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201######.((Please
delete if not appropriate))
applications in organic synthesis, materials science,
the pharmaceutical
industry.[4]
Abstract.
A regioselective method to access fully
substituted 5-trifluoromethylthio-1,2,3-triazoles and 5-thio- and
1,2,3-triazoles from the internal alkynyl trifluoromethyl
sulfides and internal thioalkynes by a rhodium(I)-catalyzed
azide-alkyne cycloaddition (RhAAC) reaction under mild
conditions has been developed. This approach features
good compatibility with water and air, a broad substrate
scope, good functional group tolerance, high yields and
excellent regioselectivities. The high 1,5-regioselectivities
were controlled by the strong coordination between the
sulfur atom and the π-acidic rhodium. The advantages of
this method further include its applicability to gram-scale
preparation, the use of solid-phase synthesis technique, and
the mutually orthogonal CuAAC-RhAAC reaction.
Trifluoromethylthio-1,2,3-triazole offers a unique
combination of the well-known activity of the SCF3
group and the 1,2,3-triazole core, allowing better
bioactivities and bioavailabilities.[2] However, the
methods for regioselectively accessing fully
substituted trifluoromethylthio-1,2,3-triazoles are still
very limited. The Huisgen 1,3-dipolar cycloaddition
of azides and internal alkynes appears to be the most
straightforward and atom-efficient approach.[5]
However, low regioselectivities are usually obtained,
and it often requires high temperatures and long
reaction times. Since 2002, the Meldal group and the
Sharpless group independently developed copper-
catalyzed AAC (CuAAC) reactions.[6] Various
transition metal catalysts were examined in the AAC
reactions (MAAC) to solve the regioselective issues
in the preparation of the fully substituted 1,2,3-
triazoles.[7] Recently, it was reported that fully
substituted 5-thio-1,2,3-triazoles could be obtained
from azide-internal thioalkyne cycloadditions with
high 1,5-regioselectivities by RuAAC[8] or IrAAC[9]
reactions. An indirect two-step strategy with a strong
Lewis acid catalyst to prepare 5-trifluoromethylthio-
1,2,3-triazoles from bench-stable 5-stannyl triazoles
via a Cu-catalyzed interrupted click reaction was
disclosed by Xu’s group (Scheme 1a).[10]
Keywords: 5-trifluoromethylthio-1,2,3-triazoles; 5-thio-
1,2,3-triazoles; rhodium; regioselectivity; mild conditions
Recently, trifluoromethanesulfenyl groups (SCF3)
have attracted increasing interest due to their unique
properties, such as their extremely high lipophilicity
and strong electron-withdrawing effects.[1] The
introduction of this functionality to the parent
molecules is an important strategy in medicinal
chemistry and agrochemistry for increasing
bioavailability because the SCF3 group can
significantly enhance the transmembrane permeation
and metabolic stability of the organic molecules.[2]
For example, the anorectic effect of flutiorex is
approximately twice as strong as that of
fenfluramine.[3a-3c] Toltrazuril is a coccidiostatic drug
in veterinary medicine.[3d,3e] Cefazaflur, a parenteral
cephalosporin, is an important antibiotic drug.[3f,3g]
Fipronil, a widely used phenylpyrazole insecticide,
has many advantages over previous generations of
insecticides such as organophosphates, carbamates
and pyrethroids[3h, 3i] (Figure 1).
Figure 1. Selected Small Molecules with SCF3 Group.
However, the direct synthesis of fully substituted 5-
trifluoromethylthio-1,2,3-triazoles from azides and
Fully substituted 1,2,3-triazoles are important
heterocyclic scaffolds, and they have numerous
1
This article is protected by copyright. All rights reserved.

10.1002/adsc.201801216
Advanced Synthesis & Catalysis
internal alkynes in one step is still unsolved.[11]
Previously, we developed a rhodium(I)-catalyzed
AAC reaction (RhAAC) to access fully substituted
1,2,3-triazolyl-4-phosphonates with high 1,4-
regioselectivity and the iridium(I)-catalyzed AAC
reaction (IrAAC) to access fully substituted 5-amido-
1,2,3-triazoles with high 1,5-regioselectivity.[12] The
differences in the regioselectivities are derived from
the chelating effect as well as the electronic character
of the internal alkynes. Inspired by Xu, Jia, Sun,
López, Mascareñas and others’ endeavors[8-10] and as
a continuation of our pursuit of highly regioselective
AAC reactions, herein, we report the direct access to
fully substituted 5-trifluoromethylthio-1,2,3-triazoles
and 5-thio-1,2,3-triazoles with excellent 1,5-
regioselectivity from internal alkynyl trifluoromethyl
sulfides and internal thioalkynes by a rhodium(I)-
catalyzed AAC (RhAAC) process under mild
conditions (Scheme 1c). Remarkably, the gram-scale
preparation, the application of solid-phase synthesis
technique and the orthogonal CuAAC-RhAAC
reactions underscore the advantages of this
intermolecular RhAAC method.
optimize the cycloaddition conditions using
dichloromethane (DCM) as the solvent without inert
gas protection (Table 1). The CuAAC reaction failed
to occur for substrate 1a using CuI or CuSO4 as the
catalyst, which indicated that the CuAAC and
RhAAC reactions may be mutually orthogonal (Table
1, entries 1 and 2). The RuAAC reaction proceeded
with good yield but poor regioselectivity by the
neutral Ru(II) catalyst instead of the cationic complex
(Table 1, entries 3 and 4). To our delight,
[Rh(CO)2Cl]2 was demonstrated to be the most
efficient catalyst at room temperature and afforded
desired 3a in high yield with excellent
regioselectivity (Table 1, entry 5). None of the
desired cycloaddition products were observed with
[Rh(cod)2]BF4 or [Rh(cod)Cl]2 as catalysts (Table 1,
entries 6 and 7). Rh(III) was ineffective in this
transformation (Table 1, entry 8). Encouragingly, we
found that the yield could
be further improved using chloroform as the solvent
and the absolute 1,5-regioselectivity could be
maintained (Table 1, entry 9). The yield could not be
further increased by using DCE or toluene (Table 1,
entries 10 and 11). The reaction failed to occur in
hexane (Table 1, entry 12). When the reaction
temperature was increased from room temperature to
40 °C, the yield remained similar (Table 1, entry 13).
Table 1. Optimization of the Reaction Conditions[a]
Entry
Catalyst
Solvent
Yield[b,c] 3a/3a’[b]
1
2
3
4
CuI
CuSO4
[Cp*Ru(PPh3)2Cl]
[Cp*Ru(MeCN)3]P
F6
DCM
DCM
DCM
DCM
0
0
81
-
-
6:1
-
trace
5
6
7
8
[Rh(CO)2Cl]2
[Rh(cod)2]BF4
[Rh(cod)Cl]2
[Cp*RhCl2]2
[Rh(CO)2Cl]2
[Rh(CO)2Cl]2
[Rh(CO)2Cl]2
[Rh(CO)2Cl]2
DCM
DCM
DCM
DCM
CHCl3
DCE
toluene
Hexane
CHCl3
84
0
0
>20:1
-
-
0
-
9
92
83
65
trace
90
>20:1
>20:1
>20:1
-
10
11
12
13[d]
[a]
[Rh(CO)2Cl]2
>20:1
Conditions: 1a (1.0 equiv), 2a (1.5 equiv), solvent (0.1
M), catalyst (2.5 mol%), air atmosphere, rt for 12 h.
Scheme 1. Synthesis of Fully-Substituted 5-
Trifluoromethylthio-1,2,3-triazoles.
1
[b] Determined by H NMR of the crude mixture with an
internal standard.
[c] The combined yield of 3a and 3a’ was reported.
[d] The reaction was set up at 40 °C.
For the preparation of fully substituted 5-
trifluoromethylthio-1,2,3-triazole
(3a),
internal
alkynyl trifluoromethyl sulfide (1a) and benzyl azide
(2a) were initially chosen as the model substrates to
2
This article is protected by copyright. All rights reserved.

10.1002/adsc.201801216
Advanced Synthesis & Catalysis
Table 2. Substrate Scope of the RhAAC with Internal Alkynyl Trifluoromethyl Sulfides[a]
[a] Standard conditions: 1 (1.0 equiv), 2 (1.5 equiv), CHCl3 (0.1 M), [Rh(CO)2Cl]2 (2.5 mol%), air atmosphere, for 12-24 h.
[b] Isolated yield. Regioselectivities (3/3’) were >20:1 (determined by 1H NMR of the crude reaction mixture).
[c] The reaction was set up at 60 °C for 24 h.
With the optimized conditions in hand, we explored
the substrate scope of the RhAAC reaction between
internal alkynyl trifluoromethyl sulfides 1 and azides
2. Various fully substituted 5-trifluoromethylthio-
1,2,3-triazoles were synthesized at room temperature
without inert gas protection in good yields (up to
92%) and excellent regioselectivities (Table 2). In
also achieve the RhAAC reactions in good yields
(Table 2, entries 7 and 8). Unfortunately, the reaction
failed to occur for alkyl-substituted internal alkynyl
trifluoromethyl sulfide 1i, even with an extended
reaction time and higher reaction temperature, and
this may have been due to the combination of the
unfavorable electronic and steric factors (Table 2,
entry 9). When using alkyl or aryl azides as substrates,
the desired products could be prepared in good yields
addition
to
the
(phenylethynyl)(trifluoromethyl)sulfane 1a, other
trifluoromethyl sulfides, such as p-methoxy, p-methyl, and excellent regioselectivities. Various functional
p-chloro
and
p-bromo
phenylethynyl
groups, including halogen, ester and carbonyl groups,
were well tolerated in this transformation (3j, 3l and
3n). The yield (3j) for the electron-withdrawing alkyl
azide was slightly higher (89%) than that of the
electron-donating substrate (3k) (Table 2, entries 10
and 11). When aryl azides were used instead of alkyl
azides, the yield decreased dramatically (3l) (Table 2,
entry 12). Good yields and regioselectivities were
obtained using ethyl or butyl azides (2m and 2n)
(Table 2, entries 13 and 14). The broad substrate
(trifluoromethyl)sulfanes could also smoothly
participate in the RhAAC reaction (Table 2, entries 1-
5). The yields for 3a-3e were similar, and no obvious
electronic effects were observed in these entries.
However,
when
using
p-nitrophenylethynyl
(trifluoromethyl)sulfane (1f) as the substrate, the
yield of the corresponding product (3f) was lower
than other substrates, yet the regioselectivity was
excellent (Table 2, entry 6). The meta-substituted and
ortho-substituted phenylacetylenes 1g and 1h could
3
This article is protected by copyright. All rights reserved.

10.1002/adsc.201801216
Advanced Synthesis & Catalysis
scope allows for the further modification of the fully
substituted 5-trifluoromethylthio-1,2,3-triazoles.
In addition to the internal alkynyl trifluoromethyl
sulfides 1, internal thioalkynes and internal alkynyl
selenides 4 could also undergo this RhAAC reaction
with azides 2 under mild conditions (Table 3).
Compared to the RhAAC reactions shown in Table 2,
the reaction temperature was increased to 40 °C for
the reactions shown in Table 3. Various aryl or alkyl
internal thioalkynes could participate well in this
transformation and give desired 5-thio-1,2,3-triazoles
5 in moderate to good yields. The yields (5f-5i) for
the substrates with alkyl sulfanes were slightly higher
than those of substrates with aryl sulfanes (5a-5e).
However, using aryl azide instead of alkyl azides
resulted in a moderate yield (62%) for 5k. The
RhAAC reaction could also occur for internal alkynyl
selenides, albeit in notably lower yields (5l).
products (Scheme 2c). (Azidomethyl) polystyrene
resin 2o could be employed for the solid-phase
synthesis of fully substituted 5-trifluoromethylthio-
1,2,3-triazole (3o) through the RhAAC process,
providing a powerful tool for surface modification
and heterogeneous catalysis (Scheme 2d). The
carbohydrate-derived
5-trifluoromethylthio-1,2,3-
triazole (3p) could be accessed efficiently from the
cycloaddition reaction (Scheme 2e). The orthogonal
CuAAC and RhAAC reactions were successfully
performed using benzyl azide and phenylethyl azide,
respectively.[8] Product 5m, with two triazole
moieties in one molecule, was obtained in good yield
(Scheme 2f). All of the above applications suggest
that the RhAAC reaction may be further applied in
biochemistry, medicinal chemistry, material science
and other areas.
Table 3. Substrate Scope of the RhAAC with Internal
Thioalkynes or Alkynyl Selenides[a][b]
[a]
Standard conditions: 4 (1.0 equiv), 2 (1.5 equiv), CHCl3
(0.1 M), [Rh(CO)2Cl]2 (2.5 mol%), air atmosphere, at 40
oC for 12-24 h.
[b] Isolated yield. Regioselectivities (5/5’) determined by 1H
NMR of the crude reaction mixture were >20:1.
Subsequently, the applicability of this RhAAC
reaction was investigated. The reaction could be
performed on the gram scale. Subjecting 1a (5.0
mmol, 1.01 g) to the conditions shown in Table 2
afforded 3a in 76% yield (3.8 mmol, 1.27 g) after
column purification (Scheme 2a). The ability to
conduct the AAC transformation in aqueous media is
very important for potential biological applications in
the future.[13] Encouragingly, fully substituted 5-
trifluoromethylthio-1,2,3-triazole could be prepared
in water as the solvent in moderate yield (Scheme 2b).
The sulfoxyl triazole (6f) could be generated by the
subsequent controllable oxidation of the RhAAC
Scheme 2. Applications of the RhAAC Reactions.
Based on the previous experiments and theoretical
calculations for the MAAC reactions,[9, 12] a general
mechanism for the RhAAC reaction is proposed in
Scheme 3. Complex A or A’ could be generated by
the initial combination of π-acidic Rh(I) with internal
alkynyl trifluoromethyl sulfide 1. Azide 2 coordinates
with Rh by the internal nitrogen atom in
4
This article is protected by copyright. All rights reserved.

10.1002/adsc.201801216
Advanced Synthesis & Catalysis
National Natural Science Foundation of China (Nos. 21702025,
51703018). We thank Prof. Baomin Wang (Dalian University of
Technology) for his enthusiastic help.
intermediateA and A’. Oxidative cyclization yields
metallacycles B and B’. For intermediate B, the SCF3
group strongly coordinates to the Rh, stabilizing the
system and providing high 1,5-regioselectivity, which
makes intermediate B more stable than B’. Hence, the
1,4-regioisomers 3’ were not observed in this
transformation. Reductive elimination of intermediate
B affords intermediate C, which results in desired
fully substituted 5-trifluoromethylthio-1,2,3-triazole 3
with high 1,5-regioselectivity.
References
[1] For the recent examples and reviews: a) J. Zhang, J.-D.
Yang, H. Zhang, X.-S. Xue, H. Mayr, J.-P. Cheng,
Angew. Chem. Int. Ed. 2018, 57, 12690. b) P. Zhang, L.
Lu, Q. Shen, Acta Chim Sinica. 2017, 75, 744. c) S.
Barata-Vallejo, S. Bonesi, A. Postigo, Org. Biomol.
Chem. 2016, 14, 7150. d) H.-Y. Xiong, X.
Pannecoucke, T. Besset, Chem. Eur. J. 2016, 22, 16734.
e) X.-H. Xu, K. Matsuzaki, N. Shibata, Chem. Rev.
2015, 115, 731. f) C. Ni, M. Hu, J. Hu, Chem. Rev.
2015, 115, 765. g) X. Shao, C. Xu, L. Lu, Q. Shen, Acc.
Chem. Res. 2015, 48, 1227. h) K. Zhang, X.-H. Xu, F.-
L. Qing, Chin. J. Org. Chem. 2015, 35, 556. i) A. Tlili,
T. Billard, Angew. Chem. Int. Ed. 2013, 52, 6818. j) S.
Alazet, L. Zimmer, T. Billard, Angew. Chem. Int. Ed.
2013, 52, 10814.
[2] a) F. Leroux, P. Jeschke, M. Schlosser, Chem. Rev.
2005, 105, 827. b) K. Muller, C. Faeh, F. Diederich,
Science 2007, 317, 1881. c) W. K. Hagmann, J. Med.
Chem. 2008, 51, 4359. d) S. Purser, P. R. Moore, S.
Swallow, V. Gouverneur, Chem. Soc. Rev. 2008, 37,
320. e) P. Jeschke, Pest Manage. Sci. 2010, 66, 10. f) N.
A. Meanwell, J. Med. Chem. 2011, 54, 2529. g) B.
Manteau, S. Pazenok, J.-P. Vors, F. R. Leroux, J.
Fluorine Chem. 2010, 131, 140. h) V. N. Boiko,
Beilstein J Org. Chem. 2010, 6, 880. i) T. Liang, C. N.
Neumann, T. Ritter, Angew. Chem. Int. Ed. 2013, 52,
8214. j) F. Toulgoat, S. Alazet, T. Billard, Eur. J. Org.
Chem. 2014, 2415. and the references in above
literatures.
Scheme 3. Proposed Mechanism of the RhAAC Reaction.
In summary, we have developed a regioselective
method for accessing fully substituted 5-
trifluoromethylthio-1,2,3-triazoles and 5-thio-1,2,3-
triazoles from the internal alkynyl trifluoromethyl
sulfides and internal thioalkynes by a rhodium(I)-
catalyzed azide-alkyne cycloaddition (RhAAC) under
mild conditions. The proposed approach exhibits a
broad substrate scope, good functional group
tolerance, good compatibility with water and air, high
yields and excellent regioselectivities. The potential
utilities of this RhAAC reaction were demonstrated
by a gram-scale synthesis, conducting the reaction in
the aqueous media, conducting the reaction on the
solid-phase and the orthogonal CuAAC and RhAAC
reactions. Further mechanistic studies and advanced
theoretical calculations for the transition states and
intermediates of this reaction are underway in our
laboratory.
[3] a) J. F. Giudicelli, C. Richer, A. Berdeaux, Br. J.
Pharmacol. 1976, 3, 113. b) J. N. André, L. G. Dring,
G. Gillet, C. Mas-Chamberlin, Br. J. Pharmacol. 1979,
66, 506P. c) T. Silverstone, J. Fincham, J. Plumley, Br.
J. Clin. Pharmacol. 1979, 7, 353. d) P. Laczay, G.
Vörös, G. Semjén, Int. J. Parasitol. 1995, 25, 753. e) P.
Pommier, A. Keïta, S. Wessel-Robert, B. Dellac, H. C.
Mundt, Rev. Med. Vet. 2003, 154, 41. f) G. W. Counts,
D. Gregory, D. Zeleznik, M. Turck, Antimicrob. Agents
Chemother. 1977, 11, 708. g) N. Aswapokee, H. C.
Neu, Antimicrob. Agents Chemother. 1979, 15, 444. h)
R. Islam, J. W. Lynch, Br. J. Pharmacol. 2012, 165,
2707. i) A. Aajoud, M. Raveton, D. Azrou-Isghi, M.
Tissut, P. Ravanel, J. Agric. Food Chem. 2008, 56,
3732.
Experimental Section
General procedure for the synthesis of 3a: To a vial
containing [Rh(CO)2Cl]2 (2.0 mg, 0.025 equiv, 0.005
mmol) in CHCl3 (2 mL) under air was added
(phenylethynyl)(trifluoromethyl)sulfane (40.4 mg, 1 equiv,
0.2 mmol) and benzyl azide (40.2 mg, 1.5 equiv, 0.3
mmol). It was necessary to add the azide at last. The vial
was closed and the mixture was stirred at room
temperature for 12 h. The mixture was purified with flash
column chromatography (33% EtOAc in petroleum ether)
to give the pure product (59 mg, 88%) as a yellow oil.
[4] For recent examples and reviews: a) H. Amdouni, G.
Robert, M. Driowya, N. Furstoss, C. Métier, A. Dubois,
M. Dufies, M. Zerhouni, F. Orange, S. Lacas-Gervais,
K. Bougrin, A. R. Martin, P. Auberger, R. Benhida, J.
Med. Chem. 2017, 60, 1523. b) A. Lauria, R. Delisi, F.
Mingoia, A. Terenzi, A. Martorana, G. Barone, A. M.
Almerico, Eur. J. Org. Chem. 2014, 2014, 3289. c) B.
T. Worrell, J. A. Malik, V. V. Fokin, Science, 2013,
340, 457. d) B. T. Worrell, S. P. Ellery, V. V. Forkin,
Angew. Chem. Int. Ed. 2013, 52, 13037. e) P.
Acknowledgements
This work was supported by grants from the Doctoral Program
Foundation of Liaoning Province (Nos. 20170520378,
20170520274), the Fundamental Research Funds for the Central
Universities (Nos. DUT16RC(3)114, DUT18LK25) and the
5
This article is protected by copyright. All rights reserved.

10.1002/adsc.201801216
Advanced Synthesis & Catalysis
Thirumurugan, D. Matosiuk, K. Jozwiak, Chem. Rev.
2013, 113, 4905. f) S. G. Agalave, S. R. Maujan, V. S.
Pore, Chem. Asian J. 2011, 6, 2696. g) K. D. Hänni, D.
A. Leigh, Chem. Soc. Rev. 2010, 39, 1240. h) S. K.
Mamidyala, M. G. Finn, Chem. Soc. Rev. 2010, 39,
1252. i) J. C. Jewett, C. R. Bertozzi, Chem. Soc. Rev.
2010, 39, 1272. j) H. C. Kolb, K. B. Sharpless, Drug
Discovery Today 2003, 8, 1128.
[5] a) R. Huisgen, Angew. Chem. Int. Ed. 1963, 2, 565. b)
R. Huisgen, Angew. Chem. Int. Ed. 1963, 2, 633.
[6] a) C. W. Tornøe, C. Christensen, M. Meldal, J. Org.
Chem. 2002, 67, 3057. b) V. V. Rostovtsev, L. G.
Green, V. V. Fokin, K. B. Sharpless, Angew. Chem. Int.
Ed. 2002, 41, 2596. c) H. C. Kolb, M. G. Finn, K. B.
Sharpless, Angew. Chem. Int. Ed. 2001, 40, 2004. For
CuAAC Reviews: d) J. E. Hein, V. V. Fokin, Chem.
Soc. Rev. 2010, 39, 1302. e) M. Meldal, C. W. Tornøe,
Chem. Rev. 2008, 108, 2952. f) P. Wu, V. V. Fokin,
Aldrichimica Acta. 2007, 40, 7. g) J. E. Moses, A. D.
Moorhouse, Chem. Soc. Rev. 2007, 36, 1249.
[7] For recent examples and reviews: a) W. G. Kim, M. E.
Kang, J. B. Lee, M. H. Jeon, S. Lee, J. Lee, B. Choi, P.
M. S. D. Cal, S. Kang, J, -M. Kee, G. J. L. Bernardes, J.
-U. Rohde, W. Choe, S. Y. Hong, J. Am. Soc. Chem.
2017, 139, 12121. b) Y. Liao, Q. Lu, G. Chen, Y. Yu,
C. Li, X. Huang, ACS Catal. 2017, 7, 7529. c) C. Wang,
D. Ikhlef, S. Kahlal, J.-Y.Saillard, D. Astruc, Cood.
Chem. Rev. 2016, 316, 1. d) F. Wei, W. Wang, Y. Ma,
C.-H. Tung, Z. Xu, Chem. Commun. 2016, 52, 14188.
[8] P. Destito, J. R. Couceiro, H. Faustino, F. López, J. L.
Mascareñas, Angew. Chem. Int. Ed. 2017, 56, 10766.
[9] a) S. Ding, G. Jia, J. Sun, Angew. Chem. Int. Ed. 2014,
53, 1877. b) Q. Luo, G. Jia, J. Sun, Z. Lin, J. Org.
Chem. 2014, 79, 11970.
[10] a) F. Wei, T. Zhou, Y. Ma, C.-H. Tung, Z. Xu, Org.
Lett. 2017, 19, 2098. b) W. Wang, Y. Lin, Y. Ma, C.-H.
Tung, Z. Xu, Org. Lett. 2018, 20, 2956. c) W. Wang, X.
Peng, F. Wei, C.-H. Tung, Z. Xu, Angew. Chem. Int.
Ed. 2016, 55, 649.
[11] Two examples have been previously reported with
moderate yields, see: S. Alazet, L. Zimmer, T. Billard,
Angew. Chem. Int. Ed. 2013, 52, 10814.
[12] a) W. Song, N. Zheng, M. Li, K. Ullah, Y. Zheng, Adv.
Synth. Catal. 2018, 360, 2429. b) W. Song, N. Zheng,
Org. Lett. 2017, 19, 6200.
[13] a) J. Miguel-Ávila, M. Tomás-Gamasa, A. Olmos, P. J.
Pérez, J. L. Mascareñas, Chem. Sci. 2018, 9, 1947. b) Y.
Bai, X. Feng, H. Xing, Y. Xu, B. K. Kim, N. Baig, T.
Zhou, A. A. Gewirth, Y. Lu, E. Oldfield, S. C.
Zimmerman, J. Am. Chem. Soc. 2016, 138, 11077.
6
This article is protected by copyright. All rights reserved.

10.1002/adsc.201801216
Advanced Synthesis & Catalysis
COMMUNICATION
Rhodium(I)-Catalyzed Regioselective Azide-
internal Alkynyl Trifluoromethyl Sulfide
Cycloaddition and Azide-internal Thioalkyne
Cycloaddition under Mild Conditions
Adv. Synth. Catal. Year, Volume, Page – Page
Wangze Song,* Nan Zheng, Ming Li, Karim Ullah,
Junhao Li, Kun Dong and Yubin Zheng
7
This article is protected by copyright. All rights reserved.