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Current Organic Synthesis, 2020, 17, 65-72

RESEARCH ARTICLE
ISSN: 1570-1794
eISSN: 1875-6271

Current
Organic Synthesis
Tetraamminecopper(II) Sulfate Monohydrate in Oxidative Azide-olefin The Journal for Current and In-depth Reviews on Organic Synthesis

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Factor:
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Cyclo-addition and Three-component Click Reaction

BENTHAM
SCIENCE

Jasmin Sultana1 and Diganta Sarma1’*

1
Department of Chemistry, Dibrugarh University, Dibrugarh, India

ARTICLE HISTORY
Received: August 01, 2019
Revised: November 29, 2019
Accepted: December 22, 2019
DOI:
10.2174/1570179417666191223152643
Abstract: Introduction: An effective Cu-complex, [Cu(NH3) 4SO 4 • H2O] was prepared conveniently from the
inexpensive and easily available starting reagents in a simple route.
Materials and Methods: Excellent reactivity of the catalyst was observed towards two competent click-
cycloadditions: (a) oxidative cycloaddition of azides with electron-poor olefins and (b) one-pot cycloaddition
of alkynes with boronic acid and sodium azide under “click-appropriate” conditions.
Results: No external oxidant, short reaction time, high product yield, wide substrate scope, and aqueous
solvent media make the azide-olefin cycloaddition approach a greener route in contrast to the reported
methods.
Conclusion: The newly developed mild, green, and rapid three-component strategy shows product diversity
with superb yields at room temperature by reducing the synthetic process time and using only 1 mol % of the
synthesized copper complex.

Keywords: Ammoniated Cu-complex, OAOC, boronic acid, aqueous media, regioselective, 1,2,3-triazole.

1. INTRODUCTION form an unstable cycloadduct, triazoline which will crush into

The 1,2,3-triazole motif is an affluent scaffold having various products as dictated by reaction conditions [16]. Conversion
incorporation into a vast number of biologically and pharma- of unstable triazoline intermediates into the stable aromatic triazole
derivatives can be achieved by two different paths: (a) eliminative
Current Organic Synthesis

ceutically active molecules [1]. Hydrogen bonding potential to

bioactive targets and high stability to metabolic degradations are the
properties that have disclosed it as an attractive and efficient
connection in biological systems. Evolution of “click reactions” [2]
triggered the application of ubiquitous triazole chemistry to several
other scientific arena [3], such as material science [4],
bioconjugation [5], and polymer chemistry [6].
Primarily, conventional Huisgen 1,3-dipolar azide-alkyne
cycloaddition was used to access 1,2,3-triazoles as 100% atom
economical and most straight forward synthetic route [7]. The
Huisgen method was further replaced by copper-catalyzed azide-
alkyne cycloaddition (CuAAC) and ruthenium-catalyzed azide-
alkyne cycloaddition (RuAAC) as it was unable to overcome the
stumbling blocks, such as high activation energy requirement and
poor regioselectivity [8, 9]. However, CuAAC and RuAAC
methods were found to be selective towards 1,4- and 1,5-
disubstituted 1,2,3-triazoles, respectively. In continuation, fully
substituted 1,2,3-triazoles have also been synthesized by various
synthetic approaches, such as cycloaddition of organic azides with
internal alkynes [10] and multicomponent reactions of azides with
keto-esters, activated enones, aldehydes, or nitriles [11].
As an alternative to AAC strategy, a few methods have been
reported representing the use of organic azides and olefins as
substrates such as: (a) dipolar cycloaddition with alkenes bearing a
leaving group [12], (b) organocatalytic oxidative 1,3-dipolar
cycloaddition with alkenes [13], (c) Cu-mediated cycloadditions
with olefins bearing electron-withdrawing functional groups [14].
Pioneer study on this field of research was implemented by L’abbe
and Huisgen [15] with organic azides and electron-poor olefins to
*
Address correspondence to this author at the Department of Chemistry, Dibrugarh
University, Dibrugarh-786004, Assam, India; E-mails: dsarma22@gmail.com;
dsarma22@dibruac.in
azide-olefin cycloaddition (EAOC), and (b) oxidative azide-olefin
cycloaddition (OAOC), in which elimination and oxidation occur,
respectively, next to the cycloaddition step (Scheme 1).
In the area of OAOC approach, a few copper-mediated catalytic
systems, such as CuI (DIPEA, 1,4-dioxane, O2-balloon, 85 °C)
[17], CuO-nanoparticles (DMF, 90 °C) [18], Cu(OTf)2 (DMF/
AcOH, 110 °C) [19], Cu(OAC)2 (DMF, 85 °C) [20] have been re-
ported representing the synthesis of 1,4-disubstituted and 1,4,5-
trisubstituted 1,2,3-triazoles. Nevertheless, some limitations, such
as the need for external oxidant, base, long reaction time, harmful
organic solvent, etc. are associated with these methods. Therefore,
at this juncture, we have made efforts to develop an efficient,
economical, and environmentally friendly method by employing
easily prepared tetraammine copper (II) sulfate complex for OAOC.
Although the organic azides needed for the synthesis of 1,2,3-
triazoles are generally stable, their handling is not safe because of
their deleterious nature. Isolation and purification of polyazides and
low molecular weight organic azides are also problematic in nature.
Moreover, the synthetic procedures for aryl azides from their
corresponding amine precursors are also not straightforward.
Therefore, the processes involving in situ generated organic azides
are highly desirable. The in situ prepared azides react with alkynes,
called three-component azide-alkyne cycloaddition and this
approach is advantageous in different ways: (a) avoids the waste
creation of the additional steps, (b) avoids the time consumption,
and (c) minimizes hazards.
Use of anilines [21] and aryl halides (bromides and iodides)
[22] as the synthetic precursor of aryl azides have found in the
literature for one-pot synthesis of substituted 1,2,3-triazoles.
However, due to the limited scope of these reactions, we turned our
concentration to the three-component synthesis of 1,4-disubstituted
1,2,3-triazoles using widely available and less toxic boronic acids
as the precursors of aryl azides. A number of such one-pot three-

1875-6271/20 $65.00+.00 © 2020 Bentham Science Publishers

66 Current Organic Synthesis, 2020, Vol. 17, No. 1
N Elimination [-HX]
N N
EAOC
X
Triazoline
= Ar, Bn = COOR, COR, CN etc.
Scheme 1. Eliminative and oxidative azide-olefin cycloaddition.
component methods have been reported by different groups by
using various copper-derivatives. These catalytic systems include
copper supported on Al2O3 [23], CuSO4 supported on chitosan [24],
copper (I)-phosphinite complex [25], Cu(OAc)2 in the presence of
piperidine [26], Cu(II)–β-cyclodextrin complex (as a nanocatalyst)
[27], glutamate-copper catalyst supported on NiFe2O4 [28], Cu(II)-
β-cyclodextrin complex supported on Fe3O4 nanoparticle [29], etc.
Most of these methods involve lengthy and laborious methods for
the preparation of active Cu-catalysts, long reaction time, and
elevated temperature.
With the increasing command for environmentally favorable
methods, greener conditions for organic synthesis have gained
much attention in the present years. Recently, we developed a bio-
surfactant (sodium deoxycholate)-accelerated one-pot three-
component method for triazole synthesis using Cu(OAc)2 as a
catalyst [30]. As an extension of this work, we developed this
method using tetraammine copper sulphate (II) complex
[Cu(NH3)4SO4 • H2O].
This known complex, ammoniated cupric sulfate monohydrate
was prepared by treating concentrated ammonia with saturated
aqueous CuSO4 solution followed by precipitating the complex
with ethanol (Fig. 1) [31]. X-ray crystallographic analysis
confirmed the presence of [Cu(NH3)4H2O]2+ unit in the solid-state
of this complex, where the central Cu(II)-ion is bound covalently by
four ammonia molecules with an average distance of 2.05Å in a
near square planar arrangement [32]. Copper ions are linked like a
chain through the oxygen atoms and these ions and chains are
clutched together via a network of hydrogen bonding.
Concentrated
NH3
CuSO4 in H2O
EtOH (Cooled in
an ice bath)
[Cu(NH3)4 H2O]SO4 Filtration of Dark purple-
complex the precipitate blue precipitate
Fig. (1). Sequential preparation of ammoniated cupric sulfate monohydrate.
Sultana and Sarma
N3
N
N Oxidation [-H2] N N
N N
OAOC X
X = NO2, OR, OAc etc.
2. MATERIALS AND METHODS
The reagents and solvents were purchased from different
commercial sources and used without further purification unless
otherwise is noted. The tetraammine copper (II) complex used in
the processes is synthesized by a reported method [33]. The organic
azides used in oxidative azide-olefin cycloaddition reaction were
also prepared by a previous reported method [34]. Purifications of
products were carried out by column chromatography using silica
gel (200-300 mesh). Analytical thin-layer chromatography was
performed using silica gel 60F254 plates and visualized with UV
light. 1H NMR (500 MHz), 13C NMR (125 MHz) were recorded on
a Bruker Advance 500 MHz spectrometer using TMS as an internal
standard. For some products, 1H NMR (600 MHz) and 13C NMR
(150 MHz) were recorded on a Bruker Advance 600 MHz
spectrometer. Chemical shifts are reported in parts per million
(ppm, δ) downfield from residual solvent peaks and coupling
constants are reported as Hertz (Hz). Splitting patterns are
designated as: s = singlet, d = doublet, t = triplet, q = quartet, m =
multiplet, etc. Melting points were determined on a Büchi B-540
melting point apparatus.
3. EXPERIMENTAL
3.1. General Procedure for Oxidative Azide-olefin
Cycloaddition
To a mixture of [Cu(NH3)4SO4 • H2O] (10 mol %) and β-
cyclodextrin (5 mol %) in 2 ml of DMSO:H2O (1:1), 1.0 equiv. of
organic azide (0.377 mmol) and 1.5 equiv. of olefin (0.565 mmol)
were added and allowed to stir at 85 °C for 4 h. After completion of
the reaction, it was extracted with ethyl acetate (2x20 mL), washed
with deionized water, dried over anhydrous sodium sulfate, and
concentrated under vacuum, which on column chromatography
(ethyl acetate:hexanes) afforded the desired product.
3.2. General Procedure for One-pot Three-component Cyclo-
addition
To a mixture of Cu-complex (1 mol %), phenylboronic acid
(0.369 mmol), sodium azide (1.107 mmol), phenyl acetylene (0.369
mmol), and K3PO4 (0.738 mmol), 2 mL of DMSO: H2O (1:10)
mixture was added and stirred at room temperature for 1 h. After
completion of the reaction, it was extracted with ethyl acetate (2×10
mL), washed with brine, dried over anhydrous sodium sulfate, and
concentrated under vacuum, which on column chromatography
(ethyl acetate: hexanes) afforded the desired product. The products
were then characterized by NMR spectroscopy.
Tetraamminecopper(II) Sulfate Monohydrate in Oxidative Azide-olefin Cycloaddition Current Organic Synthesis, 2020, Vol. 17, No. 1 67

Table 1. Optimization of reaction conditions for OAOC a .

N
N3 O Ph N N
Cu-source, additive
+
O solvent, air, heat, 4 hr OMe
O
1a 2a 3a

Entry Catalyst Additive Solvent Yield of 3a (%)b

1 Cu-complex β-cyclodextrin Toluene 51

2 Cu-complex β-cyclodextrin H2O 65

3 Cu-complex β-cyclodextrin DMSO 70

4 Cu-complex β-cyclodextrin DMSO:H2O (1:2) 80

5 Cu-complex β-cyclodextrin DMSO:H2O (1:1) 91

6 Cu-complex CTAB DMSO:H2O (1:1) 84

7 Cu-complex TBAB DMSO:H2O (1:1) 70

8 Cu-complex CPC DMSO:H2O (1:1) 68

9 CuI β-cyclodextrin DMSO:H2O (1:1) 20

10 CuCN β-cyclodextrin DMSO:H2O (1:1) trace

11 CuBr β-cyclodextrin DMSO:H2O (1:1) trace

12 Cu(OAc)2 β-cyclodextrin DMSO:H2O (1:1) 80

13 Cu-complex β-cyclodextrin DMSO:H2O (1:1) 81c, 0d

14 Cu-complex β-cyclodextrin DMSO:H2O (1:1) 85e, 70f

15 Cu-complex β-cyclodextrin DMSO:H2O (1:1) 81g, 90h

[a]
Reaction conditions: 1a (1.0 equiv., 0.377 mmol), 2a (1.5 equiv., 0.565 mmol), catalyst (10 mol %), and additive (5 mol %) were heated for 4 hrs in 2 ml solvent. [b] Product yields.
[c]
Yield of 3a using 5 mol % of Cu-complex. [d] 0 mol % of Cu-complex was employed. [e] Yield of 3a using 2 mol % of β-cyclodextrin. [f ] No β-cyclodextrin was employed.
[g]
Reaction was carried out at 70 0C. [h] Reaction was carried out at 100 0C.

4. RESULTS AND DISCUSSION
Facile reaction kinetics and biocompatibility of the CuAAC
process have made it widely acceptable as a novel and robust way
for functionalizing biomolecules. However, the problem of
cytotoxicity of active copper species has been a tenacious limitation
to carry out these Cu-catalyzed reactions [35]. Therefore, in order
to get out of this problem, Gary R. Abel and coworkers used the
qPCR (quantitative polymerase chain reaction) method and studied
the oxidative damage to a DNA strand under varying conditions
used for CuAAC reactions [36]. They discovered that the use of
DMSO in water (10% mixture) can reduce the extent of oxidative
damage by two orders of magnitude. Low toxicity and the tendency
to shield the living cells from the damage mediated by reactive
oxygen species may establish the solvent, DMSO in water to be a
feasible way to protect cells during in vitro and in vivo CuAAC
bioconjugations. Motivated by this report, here we are trying to use
the DMSO-H2O mixtures as a reliable and useful solvent media for
(a) oxidative azide-olefin cycloaddition reaction and (b) one-pot
three-component method for synthesis of 1,4-disubstituted and
1,4,5-trisubstituted 1,2,3-triazoles.
As a practical alternative to alkynes, olefins were chosen to
access these significant molecules because they are less expensive
and easy to synthesize. At the outset, the reaction was analyzed by
using phenyl azide and methyl acrylate as a representative substrate
in toluene. The prepared Cu-complex in the presence of the phase
transfer catalyst, β-cyclodextrin afforded 51% isolated yield of the
respective 1,4-disubstituted triazole molecule at 85 °C (Table 1
entry 1). Satisfied with that outcome, we optimized the reaction in
terms of different solvent systems, additives, and Cu-species. The
solvents, water, and DMSO both were observed to be suitable for
our model reaction (Table 1 entries 2 and 3). We decided to
perform the reaction in DMSO-H2O mixtures. With the increase in
the amount of DMSO in the DMSO-H2O mixtures, the reaction
yield was observed to increase and the best yield was detected by
using 1:1 mixture of DMSO in water (Table 1 entries 4 and 5).
Fixing DMSO-H2O mixture (1:1) as the best solvent system the
reaction was optimized with respect to some different additives
(phase transfer catalysts): CTAB (cetyl trimethylammonium
bromide), TBAB (tetra-n-butylammonium bromide), and CPC
(cetylpyridinium chloride) (Table 1 entries 6- 8). The additive, β-
cyclodextrin was found to be superior to the other additives as they
furnished a comparatively higher yield of 3a. Next, the reaction was
analyzed with regard to different copper-salts, such as CuI, CuCN,
CuBr, and Cu(OAc)2 (Table 1 entries 9-12). Very small amounts of
the products were noticed in the presence of CuI, CuCN, and CuBr.
When Cu(OAc)2 was chosen as the catalyst, the yield was increased
to 80 %. Thus, among the catalysts tested for the reaction, the
synthesized Cu-complex was selected as the best catalyst as it gave
the best yield of the product (90 %) under the same reaction
68 Current Organic Synthesis, 2020, Vol. 17, No. 1 Sultana and Sarma

Table 2. Substrate scope of azides with terminal and internal olefinsa, b.

R N
N N
R N3 + X
Cu-complex (10 mol %) X
β-cyclodextrin (5 mol %)
O
DMSO:H2O (1:1) N
R
85 °C, 4hr N N
R N3 +
O
R= Ar, Bn X=COOR, CN
1 2 3

N N OBun
N N OMe N N OEt
N
N N O
O O

3c, 94%
3a, 91% 3b, 93%

N N
N N OMe N N OEt
CN
N
N N
O O

Cl Cl
3d, 79%
3e, 92% 3f, 86%

N OEt N N OEt N N OMe

N
N N N
O O O

F H3C H3C
3g, 82% 3h, 86% 3i, 81%

N N O O2N N O2N
N O N N
N OMe
N N
O
H3C
3k, 84% 3l, 85%
3j, 83%
O2N N
N OBun
- N -
O
3m, 75%
[a]
Reaction conditions: Azide (1 equiv), olefin (1.5 equiv), Cu-complex (10 mol %), and the additive β-cyclodextrin (5 mol %) were heated at 85 0C in DMSO/H20 mixture (2 ml)
under atmospheric condition. [b] Isolated yields of products.

conditions. In addition, catalyst loading also played an important
role in the efficiency of the reaction (Table 1 entry 13). Dropping
the quantity of the catalyst from 10 mol % to 5 mol % showed a
decrease in the yield of the product to 81%. Apparently, no product
was detected in the absence of a catalyst (Table 1 entry 13). A
pronounced temperature effect was also noticed (Table 1 entry 17).
Reducing the temperature to 70 °C afforded a lower yield of
product (81%), while increasing the temperature to 100 °C showed
no improvement in the yield of the reaction (90%).
After optimizing the reaction conditions, different olefins
(terminal and internal) were screened with both phenyl azides and
benzyl azides to infer the efficiency of this OAOC methodology. In
this regard, the reaction was first analyzed by treating aryl azides
with an assortment of electron-poor terminal olefins. Cycloaddition
of phenyl azide with methyl acrylate, ethyl acrylate, and butyl
acrylate provided a very high yield of the corresponding ester
substituted triazole products (Table 2, 3a-c). The dipolar
cycloaddition with acrylonitrile afforded a comparative lower yield
of the product (Table 2, 3d). The presence of electron-withdrawing
functional groups (chloride and fluoride) at para-positions of the
phenyl azides were also found to be effective to provide the
respective ester-substituted triazole derivatives (Table 2, 3e-g). The
electron-donating methyl group at the para-position of phenyl azide
was also observed to be tolerated under the standard reaction
conditions and good yields of desired triazole products (3h and 3i)
were obtained. The cyclic enone, 2-cyclohexen-1-one was also
effectively clicked with 4-Me-phenyl azide and 4-NO2-benzyl azide
(3j and 3k). The reactions of nitro-substituted benzyl azide with
methyl acrylate (3l) and butyl acrylate (3m) also went well with
respective yields of 85% and 75%.
Next, to demonstrate the scope and applicability of our catalytic
system, we applied it to a one-pot three-component strategy. The
phenyl azide and phenylacetylene were allowed to react in the
presence of the copper complex, tetra amine copper (II) sulfate in
the DMSO-H2O mixture (1:10) at room temperature (Table 3, entry
1). Formation of 75% isolated yield of the desired 1,4-disubstituted
triazole product after one hour using only 1 mol % of the Cu-
complex inspired us to study the reaction further. To increase the
Tetraamminecopper(II) Sulfate Monohydrate in Oxidative Azide-olefin Cycloaddition Current Organic Synthesis, 2020, Vol. 17, No. 1 69

Table 3. Optimization of reaction conditionsa.

NaN3 N
OH Cu-source, solvent Ph N N
B +
OH Base, rt, air Ph
4a 5a 6a

Entry Catalyst Base Solvent Yield (%)b

1 Cu-complex - DMSO:H2O (1:10) 75

2 Cu-complex K2CO3 DMSO:H2O (1:10) 92

3 Cu-complex Cs2 CO3 DMSO:H2O (1:10) 86

4 Cu-complex CaCO3 DMSO:H2O (1:10) 86

5 Cu-complex K3PO4 DMSO:H2O (1:10) 96

6 Cu-complex DIPEA DMSO:H2O (1:10) 75

7 Cu-complex DBU DMSO:H2O (1:10) 93

8 Cu-complex Guanidinehydrochloride DMSO:H2O (1:10) 51

9 Cu-complex K3PO4 DMSO:H2O (1:5) 80

10 Cu-complex K3PO4 DMSO:H2O (1:1) 71

11 Cu-complex K3PO4 DMSO 52

12 Cu-complex K3PO4 H2O 96

13 Cu-complex K3PO4 CH3OH 43

14 Cu-complex K3PO4 DMF 25

15 Cu(NO3)2 K3PO4 DMSO:H2O (1:10) 82

16 CuBr K3PO4 DMSO:H2O (1:10) 55

17 CuCN K3PO4 DMSO:H2O (1:10) 67

18 CuI K3PO4 DMSO:H2O (1:10) 69

19 Cu-complex K3PO4 DMSO:H2O (1:10) 73c, 0d

[a]
Reaction conditions: 4a (1.0 equiv., 0.369 mmol), 5a (1.0 equiv., 0.369 mmol), NaN3 (3.0 equiv., 1.107 mmol), catalyst (1 mol %), and base (2.0 equiv.) were allowed to react at
rt. [b] Product yields. [c] Yield of 6a employing 0.5 mol % of the Cu-complex. [d] No Cu-source.

efficiency of the catalyst, different bases were added to the reaction
mixture and analyzed the reaction after one hour (Table 3, entries 2-
8). The highest yield (96%) was observed by employing potassium
phosphate (K3PO4) as an additive (Table 3, entry 5). To standardize
the condition of the reaction a sequence of experiments were
carried out by varying the copper source, catalyst loading, and
solvent system. Screening of different solvent systems showed that
the reactants did not react well in the presence of DMSO, CH3OH,
and DMF (Table 3, entries 11, 13, and 14). 96% yield of the
product was observed by employing the polar, easily available,
harmless, and economical solvent water under the same reaction
conditions (Table 3, entry 12). However, from solubility perception,
the DMSO-H2O mixtures were selected as the best solvent system
for this CuAAC reaction. As increasing the DMSO content in the
mixture showed a decrease in the product yield, further experiments
were carried out in 1:10 mixture of this solvent. Analysis of a few
more Cu-sources, such as Cu(NO3)2, CuBr, CuCN, and CuI
provided the respective triazoles with 82%, 45%, 67%, and 69%
yields, respectively (Table 3, entry 15-18). Again, decreasing the
amount of catalyst from 1 mol % to 0.5 mol % resulted in a
decrease in reaction rate (Table 3, entry 19).
The screened conditions were then applied to the one-pot three-
component strategy by varying the substrates (boronic acid and
alkyne). Different phenyl boronic acids (both substituted and
unsubstituted) were successfully treated with functionalized alkynes
(both aliphatic and aromatic) and sodium azide leading to 81-96%
isolated yields of products under the optimized conditions.
As displayed in Table 4, the reactions proceeded swiftly in the
presence of a series of structurally diverse phenyl boronic acids by
furnishing very high yields of products. The aliphatic terminal
alkynes were treated successfully with aryl boronic acids (Table 4,
entries 6b, 6c, and 6e). The internal alkyne, DMAD provided 93%
yield of the desired fully substituted triazole at room temperature
(Table 4, entry 6d). Satisfactory yields of products were observed
in the presence of both electron-donating and electron-withdrawing
functional groups on the aromatic ring of phenyl boronic acid and
no difference in yields was observed regarding the substitution
pattern and electronic nature of the aryl moiety. Finally, testing
heteroaryl boronic acids as a coupling partner with aromatic alkyne
under the above-optimized click cyclization reaction gave the
desirable outcome (Table 4, entries 6m, 6n).
CONCLUSION
In conclusion, the efficiency of the homogeneous, robust, and
air-stable copper amine complex has been explored in the field of
triazole synthesis. Relying on this Cu-complex, two adequate
catalytic systems have been developed for dipolar cycloaddition of
electron-deficient olefins with organic azides and alkynes with in
situ generated azides. The Cu-catalyzed azide-olefin cycloaddition
reaction has not been studied so far and our method can be a
70 Current Organic Synthesis, 2020, Vol. 17, No. 1 Sultana and Sarma

Table 4. Substrate scope of three-component reactiona .

OH Cu-complex (1 mol %) N N
B + R' N
R OH K3PO4, DMSO:H2O (1:10) R'
R
NaN3
4 5 6

N N N
N N N
O
N N N O
Ph

6a, 96% 6b, 95% 6c, 85%

N O OEt
N N N N N
N N N
O O
O
O H3C H3CO
6d, 93% 6e, 81% 6f, 95%

N N N N N N
H3C N N N

NC F
6g, 90% 6h, 88% 6i, 87%

N N N N N N
N Br N Cl N

Cl
6j, 92% 6k, 96% 6l, 91%

N N N N
S O N
N -

6m, 81 % 6n, 86 %
[a]
Reaction conditions: 4 (1.0 equiv., 0.369 mmol), 5 (1.0 equiv., 0.369 mmol), NaN3 (3.0 equiv., 1.107 mmol), Cu-complex (1 mol %), and K3PO4 (2.0 equiv.) were allowed to react
in DMSO/H2O (1:10) at rt. [b] Isolated yields.

potential substitute for the existing methods because of low reaction CONFLICT OF INTEREST
time and green solvent media. The need for no external oxidant for The authors declare no conflict of interest, financial or
oxidative dehydrogenation step and formation of “click-friendly” otherwise.
products make this strategy green. To the best of our knowledge, it
is the first ligated homogeneous copper complex-mediated system
for the OAOC approach. The novel one-pot cascade synthetic ACKNOWLEDGEMENTS
strategy developed by employing low catalyst loading was also Declared none.
efficiently applied for the regio-controlled synthesis of a variety of
triazole products. We hope that the versatility and green credentials
SUPPLEMENTARY MATERIAL
of these protocols will make them more attractive to organic
synthesis. Supplementary material is available on the publisher’s website
along with the published article.
CONSENT FOR PUBLICATION
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