Metal-free, highly regioselective sulfonylation of NH-1,2,3-triazoles with sodium sulfinates and thiosulfonates

Article abstract of DOI:10.1016/j.tetlet.2018.04.023

A convenient and metal-free protocol for the highly regioselective sulfonylation of NH-1,2,3-triazoles is described. A range of readily accessible NH-1,2,3-triazoles were sulfonylated with various aryl sulfinates in the presence of molecular iodine. The scope was extended to thiosulfonates as an efficient sulfonylating agent and nitrochromene derived triazoles were also explored for selective N-sulfonylation. A variety of synthetically viable N²-sulfonyl triazoles were obtained in moderate to high yields with excellent regioselectivities via N–S bond construction under mild reaction conditions.

Full text of DOI:10.1016/j.tetlet.2018.04.023

Accepted Manuscript
Metal-free, highly regioselective sulfonylation of NH-1,2,3-triazoles with so-
dium sulfinates and thiosulfonates
Raju Jannapu Reddy, Angothu Shankar, Md. Waheed, Jagadeesh Babu
Nanubolu
PII:
S0040-4039(18)30481-7
https://doi.org/10.1016/j.tetlet.2018.04.023
TETL 49886
DOI:
Reference:
Tetrahedron Letters
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Received Date:
Revised Date:
Accepted Date:
15 February 2018
27 March 2018
10 April 2018
Please cite this article as: Reddy, R.J., Shankar, A., Waheed, Md., Nanubolu, J.B., Metal-free, highly regioselective
sulfonylation of NH-1,2,3-triazoles with sodium sulfinates and thiosulfonates, Tetrahedron Letters (2018), doi:
https://doi.org/10.1016/j.tetlet.2018.04.023
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Metal-free, highly regioselective sulfonylation of NH-1,2,3-triazoles with sodium
sulfinates and thiosulfonates
Raju Jannapu Reddy,* Angothu Shankar, Md. Waheed and Jagadeesh Babu Nanubolu

1
Tetrahedron Letters
Metal-free, highly regioselective sulfonylation of NH-1,2,3-triazoles with sodium
sulfinates and thiosulfonates
Raju Jannapu Reddy,*,a Angothu Shankar,a Md. Waheeda and Jagadeesh Babu Nanubolub
a Department of Chemistry, Osmania University, Hyderabad 500 007, India. E-mail: rajuchem77@osmania.ac.in; rajuchem08@yahoo.co.in
b Centre for X-ray Crystallography, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, India.
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
A convenient and metal-free protocol for the highly regioselective sulfonylation of NH-1,2,3-
triazoles is described. A range of readily accessible NH-1,2,3-triazoles were sulfonylated with
various aryl sulfinates in the presence of molecular iodine. The scope was extended to
thiosulfonates as an efficient sulfonylating agent and nitrochromene derived triazoles were also
explored for selective N-sulfonylation. A variety of synthetically viable N2-sulfonyl triazoles
were obtained in moderate to high yields with excellent regioselectivities via N-S bond
construction under mild reaction conditions.
Available online
Keywords:
Iodine
Sodium sulfinates
Sulfonylation
Thiosulfonates
Triazoles
2009 Elsevier Ltd. All rights reserved.
Amongst
five-membered
heteroaromatic
On the other hand, the bench-stable, odourless and
non-hygroscopic sodium sulfinates12 have been employed
for the formation of N-S bonds with primary and secondary
amines.13 In particular, the molecular iodine-mediated
synthesis of sulfonamides13b-e attracted our attention because
the reagents are inexpensive, non-toxic, and easy to handle.
To the best of our knowledge, the sulfonylation of NH-1,2,3-
triazoles is unexplored. Therefore, this fact motivated us to
develop a new strategy for the synthesis of N2-sulfonyl
1,2,3-triazoles via the iodine-mediated regioselective
sulfonylation of NH-1,2,3-triazoles (Scheme 1c).
compounds, 1,2,3-triazoles continue to occupy an important
place in synthetic organic chemistry,1 medicinal chemistry,2
functional materials3 and other fields.4 Numerous reliable
methodologies have been developed for the synthesis of N1-
substituted 1,2,3-triazoles, as exemplified by the ‘click’
reaction of organic azides with alkynes;5 the condensation of
organic azides with activated alkenes;6 multicomponent
strategies;7 and azide-free syntheses.8 Additionally, the
organocatalyzed cycloaddition reactions of activated
carbonyl compounds with organic azides to generate 1,4,5-
trisubstituted 1,2,3-triazoles has grown remarkably in recent
years.9
Generally, the above methods produce either N1- or
N1´-substituted triazoles, thus the direct synthesis of N2-
substituted 1,2,3-triazoles remain little explored.10 Most N2-
substituted 1,2,3-triazoles are obtained by the manipulation
of NH-1,2,3-triazoles with suitable reactants.11 The groups
of Shi and Wang independently reported the alkylation of
4,5-disubstituted NH-1,2,3-triazoles to yield N2-derivatives
as the major isomer (Scheme 1a).11i-k Recently, Chen and co-
workers employed the NIS-mediated regioselective N2-
alkylation of NH-1,2,3-triazoles with olefins (Scheme 1b).11e
Despite these achievements, a general method is still lacking
for the synthesis of N2-sulfonyl 1,2,3-triazoles.
Consequently, we envisaged the difficulty in achieving
selective N2-sulfonylation of NH-1,2,3-triazoles being due to
low electron density at the N2 position. In this regard, it is
challenging to find a suitable sulfonylating agent to control
the regioselectivity for N2-sulfonylation.
Scheme 1. Comparison of previous studies with our work.
In recent years, N1-sulfonyl triazoles have been
used to generate diazo imines as efficient carbene
precursor in organic synthesis.14 While N1-sulfonyl triazoles
were readily obtained by the reaction of sulfonyl azides with
alkynes,15 the synthesis of N2-sulfonyl 1,2,3-triazoles has
become highly desirable. Herein, we report the
regioselective synthesis of N2-sufonyl 1,2,3-triazoles via the

2
Tetrahedron
reaction of readily available NH-1,2,3-triazoles with
corresponding tosylated triazoles (3ia-na), albeit in lower
sodium sulfinates and thiosulfonates in the presence of
iodine.
yields. The structure and regioselectivity of 3ia was further
confirmed by single-crystal X-ray data analysis (see ESI).16
17
The densely functionalised triazole (1o
)
was also a good
Our investigation began with the identification of
suitable reaction conditions to control the regioselectivity. Initial
experiments were performed with 4-methyl-5-phenyl-NH-1,2,3-
triazole (1a) and sodium p-toluenesulfinate (2a) as model
substrates using iodine (Table 1). A mixture of regioisomers
3aa/3aa' were formed in DCE, CH2Cl2 and 1,4-dioxane (Entries
1-3). Although the role of these solvents not entirely clear, the
formation of a regioisomeric mixture (3aa/3aa’) was probably
due to rapid interconversion of the isomeric triazole (N1-H and
N2-H) of 1a. Remarkably, a single regioisomer was observed for
the tosylated triazole 3aa in EtOH, EtOAc, CH3CN and THF
(Entries 4-7). Using 20 mol% and 50 mol% I2 in EtOAc the
substrate and provided the desired product 3oa in 52% yield.
Generally, mono-substituted triazoles are challenging
substrates to control the regioselectivity (see ESI for detailed
optimization studies).18 Regardless, the reaction of 4-phenyl-
NH-1,2,3-triazole (1p) and 4-tolyl-NH-1,2,3-triazole (1q
)
with 2a gave the corresponding sulfonylated products 3pa
and 3qa as a 9:1 and 4:1 mixture of inseparable
regioisomers, respectively. To our surprise, 1-naphthyl and
thiophenyl derived triazoles gave the desired products 3ra
and 3sa with high regioselectivities. Similar lower
regioselectivities were also observed using 4-aryl-1,2,3-
triazoles11a,d,f as substrates. Notably, these tosylated triazoles
o
reaction was sluggish at 60 C (Entries 8 and 9). The use of
(
3pa
-
sa) can be obtained by the debromination of 4-bromo
EtOAc/H2O (9:1) and 2a (2 equiv.) did not show any significant
improvement (Entries 10 and 11). To our delight, an excellent
yield (94%) was achieved using excess iodine (1.1 equiv.) with
2a (2 equiv.) in EtOAc at room temperature (Entry 12). The
sulfonylation of 1a was also observed with PhI(OAc)2 and KI
which provided 3aa in moderate yields (Entries 13 and 14),
whereas NBS afforded 3aa in 74% yield with excellent
regioselectivity (Entry 15).
triazoles (3ia
-
na) with high regioselectivities.11b,j
Table 2. I2-mediated sulfonylation of various NH-triazoles (1a-
) with sodium p-toluenesulfinate (2a).a,b
s
Table 1. Optimization for the sulfonylation of triazole 1a with 2a.a
Entry
Reaction conditions
Time
Yield (N2:N1)b
1
2
3
4
5
6
7
2a (2.5 eq.), I2 (1 eq.), DCE
2a (2.5 eq.), I2 (1 eq.), CH2Cl2
2a (2.5 eq.), I2 (1 eq.), Dioxane
2a (2.5 eq.), I2 (1 eq.), EtOH
2a (2.5 eq.), I2 (1 eq.), EtOAc
2a (2.5 eq.), I2 (1 eq.), CH3CN
2a (2.5 eq.), I2 (1 eq.), THF
2a (2.5 eq.), I2 (0.2 eq.), EtOAc, 60
oC
10 h
10 h
10 h
10 h
10 h
10 h
10 h
78% (15:1)
76% (16:1)
85% (12:1)
71% (1:0)
88% (1:0)
80% (1:0)
82% (1:0)
8
24 h
24 h
16 h
52% (1:0)
66% (1:0)
81% (1:0)
2a (2.5 eq.), I2 (0.5 eq.), EtOAc, 60
9
oC
2a (2.5 eq.), I2 (1 eq.), EtOAc/H2O
(9:1)
10
11
12
2a (2.0 eq.), I2 (1.0 eq.), EtOAc
2a (2.0 eq.), I2 (1.1 eq.), EtOAc
2a (2.5 eq.), PhI(OAc)2 (1 eq.),
EtOAc
16 h
16 h
84% (1:0)
94% (1:0)
a
Reagents and conditions: 1a-s (0.4 mmol, 1 eq.), sodium p-
toluenesulfinate 2a (2.0 eq.), I2 (1.1 eq.), EtOAc (2 mL), room
13
24 h
42% (1:0)
b
c
14
15
2a (2.5 eq.), KI (1 eq.), EtOAc
2a (2.5 eq.), NBS (1 eq.), EtOAc
24h
24 h
50% (1:0)
74% (1:0)
temperature.
Isolated yield after column chromatography.
Regioselectivities based on 1H NMR spectroscopic analysis (see ESI).
a
Reactions performed on a 0.2 mmol scale in solvent (1 mL) at room
temperature. Yields and regioselectivities based on the crude 1H NMR
b
To demonstrate the efficiency and practicality for
the sulfonylation of triazoles, the substrate scope was
extended to other sulfinate salts (Table 3). The reaction of 4-
spectra of 1a using 1,2,4,5-tetramethylbenzene as an internal standard.
With the optimized conditions in hand, we then
investigated the scope of the addition of various 4,5-
disubstituted triazoles with sodium p-toluenesulfinate (2a).
A broad range of mono- and disubstituted NH-1,2,3-
triazoles were suitable substrates for the synthesis of N2-
tosylated triazoles in good to high yields (Table 2). In
addition to 1a, electron-rich and electron-poor groups on the
aryl rings, such as methyl-, halo- and methoxy-substituents
methyl-NH-triazoles with 2b-d were investigated under the
standard reaction conditions to obtain sulfonyl triazoles 3(a-
c,h)b-d in high yields and with excellent regioselectivities.
Similarly, 4-bromo derived N-sulfonyl triazoles 3(i,m)b and
3l(c,d) were formed in good yields. As expected, the phenyl
(
1p), 1-naphthyl (1r) and thiophenyl (1s) derived triazoles
were also sulfonylated. The high regioselectivity may be due
to the methyl group and bromine atom blocking the N1
reaction sites. Therefore, the C4 and C5 substituents on the
triazole nucleus play an important role to provide
predominantly the N2-sulfonylated products (see ESI).
(
1b
-
g
), smoothly reacted with 2a to give the desired 2-
ga) in 74–90% yield. The
tosylated 1,2,3-trizoles (3ba
–
heteroaryl substituted triazole (1h) was also a suitable
substrate and provided the desired product 3ha in 82% yield.
Moreover, a variety of 4-bromo-5-aryl-NH-1,2,3-triazoles
Table 3. Sulfonylation of NH-triazoles using various sulfinates
(1i-n) were also compatible substrates and provided the
(
2b-d).a,b

3
yields in comparison with other triazoles (Scheme 2).
Disappointingly, these triazoles failed to react with S-phenyl
4-methylbenzene-sulfonothioate 4a under the standard
reaction conditions.
Scheme 2. Sulfonylation of nitrochromene derived triazoles.
Reagents and conditions: 5a,b (0.4 mmol, 1 eq.), 2a (2.0 eq.), I2 (1.1
eq.), EtOAc (2 mL), room temperature, 24 h; 5a,b (0.4 mmol, 1 eq.),
4a (2.0 eq.), I2 (1.1 eq.)/Cs2CO3 (1 eq.), CH3CN (2 mL), 60 oC, 24 h.
a Isolated yield after column chromatography.
a
To gain insight to understand the reaction
mechanism, control experiments were performed (Scheme
3). Using the radical scavenger TEMPO under the standard
conditions, product 3aa was observed in trace amounts,
indicating that the reaction should proceed via a free-radical
pathway (Scheme 3a). The known relatively unstable
sulfonyl iodide, tosyl iodide (TsI),20 was prepared by the
reaction of 4-methylbenzene sodium sulfinate 2a with
molecular iodine. Subsequent treatment with 1a provided
the desired product in 48% yield (Scheme 3b). To further
understand the role of iodine, triazole 1a was treated with I2
to presumably form the corresponding N-iodotriazole,
followed by subsequent addition of sulfinate salt 2a to
afford 3aa in 75% yield (Scheme 3c). Overall, these results
suggest that the molecular iodine might be activating both
reactants to form the N2-sulfonylated products.
Reagents and conditions: triazole (0.4 mmol, 1 eq.), sodium sulfinate
2a (2.0 eq.), I2 (1.1 eq.), EtOAc (2 mL), room temperature. b Isolated
yield after column chromatography. Regioselectivities based on H
NMR spectroscopic analysis (see ESI).
c
1
Recently, Jang and co-workers elegantly utilised
thiosulfonates as a sulfonylating agent.19 With a view to
understand the generality of the presented methodology,
thiosulfonates 4a and 4b were also examined. The reaction
optimization was revisited using 1a and 4a as model
compounds; the best results were achieved using
combination of I2 (1.1 equiv.)/Cs2CO3 (1 equiv.) or NBS (2
equiv.)/Cs2CO3 (1 equiv.) in acetonitrile at 60 C (Table 4).
a
o
The sulfonylation of various triazoles with 4a provided the
desired N2-tosylated triazoles 3(a-c,e-g)a in high yields.
Additionally, using 4b, the corresponding N2-sulfonylated
triazoles 3(a-c)b were obtained in good to high yields. The
bromo derived triazole (1i) afforded 3ib in only 25% yield,
while the 4-phenyl (1p) and 4-thiophenyl (1s) triazoles were
produced in trace amounts.
Table 4. Sulfonylation of NH-triazoles using thiosulfonates (4a
and 4b).a,b
Scheme 3. Control experiments for mechanistic studies.
On the basis of experimental results and literature
precedence,13b-e
a
plausible mechanism was proposed
(Scheme 4). In path A, the reaction of sodium sulfinate
2
with molecular iodine could lead to the corresponding
sulfonyl iodide intermediate.20 The homolytic cleavage of
sulfonyl iodide generates a sulfonyl radical which reacts
with the internal nitrogen (N2) of the triazole. Similarly, in
path B, iodine might activate the internal nitrogen (N2) of
a Reagents and conditions: triazole (0.4 mmol, 1 eq.), thiosulfonate 4a/b
(2.0 eq.), I2 (1.1 eq.)/Cs2CO3 (1 eq.) or NBS (2 eq.)/Cs2CO3 (1 eq.),
b
CH3CN (2 mL), 60 oC, 24 h.
Isolated yield after column
triazole
1
to give the N2-iodotriazole, which reacts with
to give product . Although the
chromatography. c Reaction conducted with NBS (see ESI).
sodium sulfinates
2
3
To understand the generality of sulfonylation, the
reaction scope was extended to nitrochromene derived
triazoles. Accordingly, the sulfonylation of 5a and 5b with
sodium p-toluenesulfinate 2a under the standard reaction
conditions gave N2-tosylated triazoles 6a and 6b with lower
relatively low electron density at N2 in comparison with the
two terminal nitrogens (N1 and N1'),11a,k the high N2-
selectivity would be favoured due to the steric hindrance of
the C4 and C5 substituents.

4
Tetrahedron
M., Gujral, J., Reddy, G. S., Chem.-Eur. J., 2015, 21, 16775; (c)
Ramachary, D. B., Shashank, A. B., Karthik, S., Angew. Chem., Int.
Ed., 2014, 53, 10420; (d) Li, W., Du, Z., Huang, J., Jia, Q., Zhang,
K., Wang, J., Green Chem., 2014, 16, 3003; (e) Wang, L., Peng, S.,
Danence, L. J., Gao, Y., Wang, J., Chem. - Eur. J., 2012, 18, 6088.
10 (a) Kalisiak, J., Sharpless, K. B., Fokin, V. V., Org. Lett., 2008, 10,
3171; (b) Kamijo, S., Jin, T., Huo, Z., Yamamoto, Y., J. Org. Chem.,
2004, 69, 2386; (c) Kamijo, S., Jin, T., Huo, Z., Yamamoto, Y., J.
Am. Chem. Soc., 2003, 125, 7786.
Scheme 4. Plausible mechanism for the N2-sulfonylation of NH-
triazoles.
11 For the selective N2-functionalization of triazoles, see: (a) Wei, H.,
Hu, Q., Ma, Y., Wei, L., Liu, J., Shi, M., Wang, F., Asian J. Org.
Chem., 2017, 6, 662; (b) Deng, X., Lei, X., Nie, G., Jia, L., Li, Y.,
Chen, Y., J. Org. Chem., 2017, 82, 6163; (c) Motornov, V. A.,
Tabolin, A. A., Novikov, R. A., Nelyubina, Y. V., Ioffe, S. L.,
Smolyar, I. V., Nenajdenko, V. G., Eur. J. Org. Chem., 2017, 6851;
(d) Bhagat, U. K., Kamaluddin, Peddinti, R. K., Tetrahedron Lett.,
2017, 58, 298; (e) Zhu, L.-L., Xu, X.-Q., Shi, J.-W., Chen, B.-L.,
Chen, Z., J. Org. Chem., 2016, 81, 3568; (f) Zhu, L.-L., Xu, X.-Q.,
Shi, J.-W., Chen, B.-L., Chen, Z., J. Org. Chem., 2016, 81, 3568; (g)
Wen, J., Zhu, L.-L., Bi, Q.-W., Shen, Z.-Q., Li, X.-X., Li, X., Wang,
Z., Chen, Z., Chem. Eur. J., 2014, 20, 974; (h) Ueda, S., Su, M.,
Buchwald, S. L., Angew. Chem., Int. Ed., 2011, 50, 8944; (i) Wang,
X. J., Zhang, L., Krishnamurthy, D., Senanayake, C. H., Wipf, P.,
Org. Lett., 2010, 12, 4632; (j) Wang, X. J., Zhang, L., Lee, H.,
In conclusion, we have successfully developed a
highly regioselective, iodine-mediated sulfonylation reaction
of NH-1,2,3-triazoles using sodium sulfinates and
thiosulfonates to provide N-sulfonylated triazoles in
moderate to high yields. This protocol is operationally
simple and possesses a wide substrate scope, permitting the
synthesis of a range of N2-sulfonyl triazoles which can be
difficult to prepare by other methods.
Acknowledgements
Haddad, N., Krishnamurthy, D., Senanayake, C. H., Org. Lett., 2009
11, 5026; (k) Chen, Y., Liu, Y., Petersen, J. L., Shi, X., Chem.
Commun., 2008, 3254.
,
We thank SERB-ECR (File No. ECR/2015/000053), New
Delhi for financial assistance. RJR thanks to UGC for
faculty position under Faculty Recharge Programme. AS
and MW thanks to CSIR and UGC, New Delhi, respectively
for their research fellowship.
12 For a review on sulfinate salts, see: Aziz, J., Messaoudi, S., Alami,
M., Hamze, A., Org. Biomol. Chem., 2014, 12, 9743.
13 For the synthesis of sulfonamides using sodium sulfinates, see: (a)
Jiang, Y.-y., Wang, Q.-Q., Liang, S., Hu, L.-M., Little, R. D., Zeng,
C.-C., J. Org. Chem., 2016, 81, 4713; (b) Wei, W., Liu, C., Yang, D.,
Wen, J., You, J., Wang, H., Adv. Synth. Catal., 2015, 357, 987; (c)
Buathongjan, C., Beukeaw, D., Yotphan, S., Eur. J. Org. Chem.,
2015, 1575; (d) Yang, K., Ke, M., Lin, Y., Song, Q., Green Chem.,
2015, 17, 1395; (e) Pan, X., Gao, J., Liu, J., Lai, J., Jiang, H., Yuan,
G., Green Chem., 2015, 17, 1400.
14 For representative recent reviews, see: (a) Jia, M., Ma, S., Angew.
Chem., Int. Ed., 2016, 55, 9134; (b) Davies, H. M. L., Alford, J. S.,
Chem. Soc. Rev., 2014, 43, 5151; (c) Chattopadhyay, B., Gevorgyan,
V., Angew. Chem., Int. Ed., 2012, 51, 862.
References and Notes
1
For an excellent review on triazole applications, see: Huang, D.,
Zhao, P., Astruc, D., Coord. Chem. Rev. 2014, 272, 145.
2
Selected articles: (a) Mohammed, I., Kummetha, I. R., Singh, G.,
Sharova, N., Lichinchi, G., Dang, J., Stevenson, M., Rana, T. M., J.
Med. Chem. 2016, 59, 7677; (b) Bai, H., Zhu, P., Wu, W., Li, J., Ma,
Z., Zhang, W., Cheng, Y., Du, L., Li, M., Med. Chem. Commun.
2015, 6, 418; (c) Hsieh, H. Y., Lee, W. C., Senadi, G. C., Hu, W. P.,
Liang, J. J., Tsai, T. R., Chou, Y. W., Kuo, K. K., Chen, C. Y., Wang,
J. J. J. Med. Chem., 2013, 56, 5422; (d) Thirumurugan, P., Matosiuk,
D., Jozwiak, K. Chem. Rev., 2013, 113, 4905.
15 For the synthesis of N1-sulfonyl-4-substituted triazoles, see: (a) Cano,
I., Nicasio, M. C., Pérez, P. J., Org. Biomol. Chem., 2010, 8, 536; (b)
Wang, F., Fu, H., Jiang, Y., Zhao, Y., Adv. Synth. Catal., 2008, 350,
1830. 46; For synthesis of N1-sulfonyl-5-substituted triazoles: (c)
Meza-Aviña, M. E., Patel, M. K., Lee, C. B., Dietz, T. J., Croatt, M.
P., Org. Lett., 2011, 13, 2984.
3
For selected articles on materials, see: (a) Reed, D. A., Xiao, D. J.,
Gonzalez, M. I., Darago, L. E., Herm, Z. R., Grandjean, F., Long, J.
R., J. Am. Chem. Soc., 2016, 138, 5594; (b) Sood, R., Donnadio, A.,
Giancola, S., Kreisz, A., Jones, D. J., Cavaliere, S., ACS Appl. Mater.
Interfaces, 2016, 8, 16897; (c) Shida, N., Ishiguro, Y., Atobe, M.,
Fuchigami, T., Inagi, S., ACS Macro Lett., 2012, 1, 656.
16 The crystal structure of 3ia was deposited in the Cambridge
Crystallographic Data Centre (CCDC# 1816730).
17 Reddy, R. J., Waheed, Md., Karthik, T., Shankar, A., New J. Chem.,
2018, 42, 980.
18 The N2-regioselectivity of 3pa
, 3qa, 3sa, 3pb and 3sb was
4
5
For recent review articles, see: (a) Schulze, B., Schubert, U. S.,
Chem. Soc. Rev., 2014, 43, 2522; (b) Byrne, J. P., Kitchen, J. A.,
Gunnlaugsson, T., Chem. Soc. Rev., 2014, 43, 5302.
For representative reviews, see: (a) Johansson, J. R., Beke-Somfai,
T., Stålsmeden, A. S., Kann, N., Chem. Rev., 2016, 116, 14726 and
1
established on the basis of H NMR data comparison with isomeric
triazoles reported in the literature (see ESI, Table 2).
19 (a) Shyam, P. K., Jang, H.-Y., J. Org. Chem., 2017, 82, 1761; (b)
Shyam, P. K., Son, S., Jang, H.-Y., Eur. J. Org. Chem., 2017, 5025.
20 For the preparation of tosyl iodide, see: (a) Liu, L. K., Chi, Y., Jen,
K.-Y., J. Org. Chem., 1980, 45, 406 (b) Nájera, C., Bald, B., Yus, M.,
J. Chem. Soc. Perkin Trans. 1, 1988, 1029.
references herein; (b) Liang, L., Astruc, D., Coord. Chem. Rev., 2011
,
255, 2933; (c) Hein, J. E., Fokin, V. V., Chem. Soc. Rev., 2010, 39,
1302; (d) Meldal, M., Tornøe, C. W., Chem. Rev., 2008, 108, 2952.
(a) Chen, Y., Nie, G., Zhang, Q., Ma, S., Li, H., Hu, Q., Org. Lett.,
2015, 17, 1118; (b) Li, W., Du, Z., Zhang, K., Wang, J., Green
Chem., 2015, 17, 781; (c) Li, W., Wang, J., Angew. Chem., Int. Ed.,
2014, 53, 14186; (d) Janreddy, D., Kavala, V., Kuo, C. W., Chen, C.
W., Ramesh, C., Kotipalli, T., Kuo, T. S., Chen, M. L., He, C. H.,
Yao, C. F., Adv. Synth. Catal., 2013, 355, 2918.
6
7
8
9
For recent reviews on multicomponent strategies: (a) Chen, Z., Liu,
Z., Cao, G., Li, H., Rena, H., Adv. Synth. Catal., 2017, 359, 202; (b)
Wei, F., Wang, W., Ma, Y., Tunga, C.-H., Xu, Z., Chem. Commun.,
2016, 52, 14188; (c) Hassan, S., Müller, T. J. J.. Adv. Synth. Catal.,
2015, 357, 617.
For selected reports for azide-free reactions, see: (a) Panda, S., Maity,
P., Manna, D., Org. Lett., 2017, 19, 1534; (b) Bai, H.-W., Cai, Z.-J.,
Wang, S.-Y., Ji, S.-J., Org. Lett., 2015, 17, 2898; (c) Wan, J.-P., Cao,
S., Liu, Y., J. Org. Chem., 2015, 80, 9028; (d) Chen, J.-H., Liu, S.-R.,
Chen, K., Chem.-Asian J., 2010, 5, 328.
Selected reports: (a) Thomas, J., Jana, S.. Liekens, S., Dehaen, W.,
Chem. Commun., 2016, 52, 9236; (b) Ramachary, D. B., Krishna, P.

5
Highlights:

A variety NH-triazoles have been
accessed
for
regioselective
sulfonylation.



The metal-, ligand- and additive-free
synthesis of N2-sulfonyl triazoles.
A wide range of N2-sulfonyl triazoles
have been prepared readily.
This
method
is
a
simple,
straightforward and broad substrate
scope compatibility.