Syntheses of Bis-Triazole Linked Carbohydrate Based Macrocycles and Their Applications for Accelerating Copper Sulfate Mediated Click Reaction

Article abstract of DOI:10.1002/ejoc.201801714

Macrocyclic compounds play an important role in many research fields including drug discovery and development, bioorganic chemistry, and materials sciences. Carbohydrate-based macrocycles are important compounds with unique structures and many potential a

Full text of DOI:10.1002/ejoc.201801714

A Journal of
Accepted Article
Title: Syntheses of bis-triazole linked glycomacrocycles and their
applications for accelerating copper sulfate mediated click
reaction
Authors: Anji Chen, Lalith P. Samankumara, Sanjeev Dodlapati, Dan
Wang, Surya Adhikari, and Guijun Wang
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: Eur. J. Org. Chem. 10.1002/ejoc.201801714
Link to VoR: http://dx.doi.org/10.1002/ejoc.201801714
Supported by

European Journal of Organic Chemistry
10.1002/ejoc.201801714
Syntheses of bis-triazole linked carbohydrate based macrocycles and their
applications for accelerating copper sulfate-mediated click reaction
Anji Chen, Dr. Lalith P. Samankumara, Sanjeeva Dodlapati, Dan Wang, Surya Adhikari, Dr.
Guijun Wang*
Department of Chemistry and Biochemistry, Old Dominion University, Norfolk, VA 23529, USA.
*
Corresponding Author:
Guijun Wang, PhD
Professor of Chemistry and Biochemistry
Old Dominion University
4
541 Hampton Boulevard
Norfolk, VA 23529-0126
Email: g1wang@odu.edu
Telephone: (757) 683-3781
Fax: (757) 683-4628
https://sites.google.com/a/odu.edu/wang-group/
1
This article is protected by copyright. All rights reserved.

European Journal of Organic Chemistry
10.1002/ejoc.201801714
Abstract
Macrocyclic compounds play an important role in many research fields including drug discovery
and development, bioorganic chemistry, and materials sciences. Carbohydrate-based macrocycles
are important compounds with unique structures and many potential applications. In this study, we
have designed and synthesized a series of 1,2,3-triazole linked and pyranose embedded
macrocycles in short steps through the copper (I) catalyzed azide and alkyne cycloaddition
reactions (CuAAC). Eight non-symmetrical glucosamine based and bis-triazole linked
macrocycles have been synthesized starting from the readily available N-acetyl-D-glucosamine.
These triazole-linked glycomacrocycles showed remarkable reaction rate accelerations for CuSO
4
mediated azide and alkyne cycloaddition reactions in aqueous mixtures. Several azides including
a sugar azide that react sluggishly with alkynes have been accelerated with the synthesized
macrocycles. The benzoylated macrocycles with three methylene linkage at anomeric positions
were most effect among the eight macrocycles.
Keywords: glycomacrocycle, N-acetyl-D-glucosamine, macrocycle synthesis, click chemistry,
copper catalysis.
2
This article is protected by copyright. All rights reserved.

European Journal of Organic Chemistry
10.1002/ejoc.201801714
Introduction
Macrocyclic frameworks are important structural features in many natural products and
pharmaceutics. Natural and synthetic macrocycles often exhibit useful biological activities that
allow them to function as drugs or lead compounds for drug discovery.1-7 They are also important
in molecular recognition and materials sciences.8,9 Among the different types of macrocyclic
compounds, carbohydrate-derived macrocycles have attracted great interest due to their unique
structures and many applications in biological sciences, materials chemistry, and supramolecular
chemistry.10-13 Selective functionalization of monosaccharides in their furanoid or pyranoid
configurations can generate diverse library of sugar-containing macrocyclic compounds. The
conformation-restricted nature of sugar ring allows the formation of chiral cavities, which are
useful for guest encapsulation and chiral recognition. Because of their unique structures and
functions, many synthetic strategies have been developed towards the construction of
carbohydrate-based macrocycles.10,14
In recent years, copper (I) catalyzed azide alkyne cyclization reaction (CuAAC), or “click
1
5
chemistry” strategy has shown great applications in many areas. The click chemistry has greatly
enabled the syntheses and study of glycoconjugates and shaped carbohydrate research.14,16-18 The
CuAAC products, typically 1,4-disubstituted 1,2,3-triazoles, are useful heterocycles that are not
passive linkers, they also have properties leading to biological activities, as ligands in catalysis,
sensors for guest recognitions, and in preparation of functional supramolecular assemblies.19-21
Because of the importance of the reaction, many efforts have been devoted to improve the reaction
scopes to include different substrates and optimize reaction conditions for biological
applications.22-24 Many synthetic methods using different copper reagents, ligands and catalysts
3
This article is protected by copyright. All rights reserved.

European Journal of Organic Chemistry
10.1002/ejoc.201801714
for the preparation of triazoles by click chemistry have been developed.25-27 Several organic
compounds that can accelerate the copper catalyzed azide alkyne cycloaddition have been
reported, including various triazole derivatives as ligands.28-31 The click chemistry has shown
remarkable utility for the construction of sugar based macrocycles typically at the last step of the
macrocyclization.32-42 A few examples of sugar based macrocycles containing the 1,2,3-triazole
linkage are shown in Figure 1. C2-symmetrical sugar based macrocycle 1 and cyclodextrin mimics
2
exhibit guest binding and recognition properties.43,44 And the galactose derived macrocycle 3
was synthesized and identified as an apoptosis inducer in leukemic cells.45
Figure 1. Examples of sugar and triazole based macrocycles with sugar in the backbone of the
cycle.
Results and Discussions
In this research, we designed and synthesized a series of novel macrocycles with the general
structure 4, containing a pyranose ring derived from N-acetyl-D-glucosamine in the backbone and
linked through two 1,4-disubstituted 1,2,3-triazoles. We have shown that certain sugar triazole
derivatives formed functional molecular assemblies and supramolecular gels.46-48 By incorporating
triazole functional groups present in supramolecular gelators into a macrocycle, we can obtain a
new class of compounds which may have interesting applications. The resulting macrocycles with
unique architectures may lead to interesting biological properties as enzyme inhibitors or they can
4
This article is protected by copyright. All rights reserved.

European Journal of Organic Chemistry
10.1002/ejoc.201801714
form molecular assemblies that may function as suitable hosts. The heterocycles in the molecules
together with the sugar ring embedded in the macrocycles form unique cavities and binding sites
for metals or ligands and can be explored for chiral recognition and catalysis.
Utilizing click chemistry strategy, we can introduce triazole functional groups to the sugar skeleton
at the anomeric position and at the 6-hydroxyl group of a pyranose such as glucose or glucosamine.
As shown in Scheme 1, glycosylation of N-acetyl-D-glucosamine 5 with chloroalkanol 6 using
BF
3
Et O as the catalyst afforded the α-anomer as the major product. Either the mixture or the pure
2
α-isomer was converted to the azide 7 as pure α-anomer. This was then converted to the tosylated
intermediates by a one pot selective tosylation followed by acylation of 3, 4-dihydroxyl groups to
afford diacetates 8. Mono click reaction of the intermediate 8a or 8b with a bis-terminal alkyne
afforded the intermediates 10A-10D. The tosyl group was then displaced with an azido group to
afford the azido alkynes 12A-12D, the key precursors used in the cyclization reaction. Compound
1
2B (R= Ac, n = 1, m = 2) was used as the intermediate for the macrocyclization test reactions,
the results are shown in Table 1. When using CuSO and sodium ascorbate (NaAsc) as the catalysts
afforded only small amount of the desired macrocycle. Using CuI and diisopropyl ethylamine
DIEA) as catalysts has resulted in better yields. The CuI catalyst loading seems to be critical to
4
(
the cyclization reaction. Through several trials we found the using 0.2 equvi of CuI in acetonitrile
at normal concentration (15 mM) at 0 °C, clean conversion to the desired product was observed
and with acceptable isolated yield of 47%. This condition was used for the synthesis of several
other macrocycles; which are named based on the numbers of hydrocarbons linking the triazoles
and the sugar ring: AM25-AM36. Besides using acetate as the protective groups, by similar
methods, we synthesized four other macrocycles: BM25-BM36.
5
This article is protected by copyright. All rights reserved.

European Journal of Organic Chemistry
10.1002/ejoc.201801714
Scheme 1. Synthesis of sugar derived macrocycles via click reaction.
6
This article is protected by copyright. All rights reserved.

European Journal of Organic Chemistry
10.1002/ejoc.201801714
Table 1. Conditions and yields for the macrocyclization of 12B through click chemistry for AM26
Conversion %
Solvent,
Concentration
mM
Yield%
isolated
Entry
Catalyst and additives
estimated by
NMR
temperature
DCM/H
2
r.t. to 50°C
THF, r.t.
O (5/1),
1
CuSO
4
0.2, NaAsc 0.4
2.8
50%
15%
2
3
4
5
6
CuI 2.0, DIEA 3.0
CuI 1.2, DIEA 3.0
CuI 1.0, DIEA 3.0
CuI 0.5, DIEA 5.0
CuI 0.2, DIEA 5.0
2.3
2.3
2.3
4.5
15
100%, mixture
polymerization
100%, mixture
100%
30%
0%
THF, reflux
THF, r.t.
28%
44%
47%
THF, r.t.
CH
3
CN, 0 °C
100%
Figure 2 shows the structures of the eight macrocycles synthesized in this study. Using Chem3D
molecular modeling, we carried out the MM2 energy minimization to obtain the conformation of
the macrocycles for the eight macrocycles. The energy-minimized conformations of the
benzoylated macrocycles are shown in Figure 3 and the acetylated macrocycles are shown in
Supplementary Information (SI) Figure S1. Typically, the distance of the two triazole rings is
around 5Å in these macrocycles. The cavities should be flexible and able to bind guest molecules
of small size, such as metal ions and amino acid derivatives. For the benzoate derivatives, the
cavity seems to be more defined comparing to the acetate derivatives due to the influence of the
aromatic phenyl group. The two benzoate shielded part of the macrocycle, this may lead to
enhanced binding towards the triazole rings. Due to the flexible linkages, the triazole orientation
can change upon binding to guest molecules or metal ions.
7
This article is protected by copyright. All rights reserved.

European Journal of Organic Chemistry
10.1002/ejoc.201801714
Figure 2. Structures of the eight macrocycles synthesized.
Figure 3. The energy minimized stable conformations of the benzoate protected macrocycles.
8
This article is protected by copyright. All rights reserved.

European Journal of Organic Chemistry
10.1002/ejoc.201801714
Since 1,2,3-triazoles have been used as ligands for CuAACs, as a proof of principle studies, we
explored the applications of these macrocycles as ligands for copper sulfate- mediated azide alkyne
cycloaddition reactions (AACs). We had carried out click reactions using 1-azido-1-deoxy--D-
glucopyranoside tetraacetate (Ac-Glc-N
3
) and 2-acetamido-2-deoxy--D-glucopyranosyl azide
3
2
,4,6-triacetate 14 with a series of alkynes previously.47,48 These reactions typically required 12-
4 h and sometimes elevated temperatures to achieve desirable products in good yields, and
phenylacetylene reacts much slower than aliphatic alkynes. The glucosamine derivative 14
typically reacts slower than Ac-Glc-N for the same alkynes. Therefore we choose compound 14
3
as the main substrate to test whether the synthesized macrocycles can catalyze the cycloaddition
reactions. We were pleased to find that these macrocycles were effective ligands in accelerating
CuSO catalyzed AACs. As shown in Table 2, the sugar azide 14 and phenylacetylene were used
4
as the substrates. With 5.0 mol% macrocycle loading in 2 h all eight compounds were effective to
accelerate the reaction to quantitative conversion without byproducts, the products were obtained
in 97% isolated yield. Without the added macrocycle ligands, the click reaction product was only
obtained in 23% conversion at 2 h. Next we screened the reactions with different amount of
macrocycle (BM35) and copper sulfate, different solvents, the results are shown in SI Table S1
and Figures S3-S4. Using 5.0 mol% macrocycle, and 5.0 mol% CuSO
with 100% conversion in 4 h, further reduction of copper amount was not effective under these
conditions. Using 20 mol% CuSO , the BM35 loading can be reduced to 2.5% without affecting
reaction rate much. Further reduction of macrocycle however was not effective. Therefore, next
we screened all macrocycle ligand loading at 2.5 mol% using EtOH/H O (1:1) as the solvent.
4
, the reaction proceeded
4
2
Interestingly all eight macrocycles showed similar catalytic effects (Table 2, Condition A), all
9
This article is protected by copyright. All rights reserved.

European Journal of Organic Chemistry
10.1002/ejoc.201801714
reactions achieved 100% conversion at 5 h. The control reaction without the ligand had 21%
conversion at 5 h.
Table 2. Effect of the macrocycle on catalyzing the click chemistry using phenyl acetylene
Condition A (2.5 mol%)
Condition B (5.0 mol%)
Entry Macrocycle Conversion
Conversion
(%) at 5 h
21
Conversion Isolated yield
(%) at 2 h
(%) at 2 h
23
(%)
N/A
97
1
2
3
4
5
6
7
8
9
none
15
AM25
AM26
AM35
AM36
BM25
BM26
BM35
BM36
55
100
100
53
100
100
98
55
100
100
98
57
100
100
98
61
100
100
98
64
100
100
98
67
100
100
97
66
100
100
97
1
0
This article is protected by copyright. All rights reserved.

European Journal of Organic Chemistry
10.1002/ejoc.201801714
For both conditions: Sugar azide (1 equiv), CuSO4 5H O (0.2 equiv), phenylacetylene (1.2
2
equiv), NaAsc (0.4 equiv). Condition A: 2.5 mol% macrocyle in EtOH/H
2
O (1:1); Condition B:
5
.0 mol% macrocyle in t-BuOH/THF/H O (1: 1: 1).
2
Using compound BM35 as the ligand, we screened reaction conditions of 14 with 1-octyne, the
results are shown in SI Table S2 and Figure S7. There was not much difference using t-
BuOH/THF/H
2
O, or t-BuOH/H
2
O, or EtOH/H O mixtures as the solvents. When 20% copper
2
sulfate and 2.0-2.5% macrocycle (as the ligand) were used, all reactions showed 100% conversion
to the product 16 within one hour. When the macrocycle loading was reduced to 1.0 mol%, either
using 0.1 or 0.2 equivalents of copper sulfate, the reaction completed within two hours. But further
reduction of the macrocycle loading to 0.5 mol% led to slower reaction rates with only 50%
conversion observed at 1 h. Based on the screening results using BM35, we used 10 mol% CuSO
4
and tested all eight macrocycles, as shown Table 3. At 5.0 mol% macrocycle loading, all but two
reactions were completed in less than 1 h, the reactions using AM35 and AM25 were completed
in 2 h. In all these reactions the desired product was obtained as the only product and the triazole
1
6 was isolated in excellent yields. The control reaction without macrocycles only proceeded with
1
9% conversion at 1 h. When we reduced the loading of the macrocycle ligands to 1.0 mol%,
BM35 and BM36 were the most efficient at accelerating the reactions, with 100% conversion to
products in 2 h, but the others were not as effective.
Based on the screening results in Tables 2 and 3, the benzoylated macrocycles (BM series) worked
better than the corresponding acetylated derivatives (AM series) with the same ring sizes. This
suggests that the peripheral modifications of the macrocycles made a difference in guest binding.
1
1
This article is protected by copyright. All rights reserved.

European Journal of Organic Chemistry
10.1002/ejoc.201801714
The modeling studies indicated that the benzoate phenyl ring contributed to aryl - stacking
interactions forcing the macrocycle to adopt a different conformation. As for ring sizes and
positions of triazoles, typically the 6 methylene spacer linked macrocycles are slightly more
effective than the corresponding 5-carbon linked systems. The alkyl spacer at the anomeric
position played an important role, the three carbon linked compounds were more effective than the
corresponding two carbon linked systems. The position of triazoles affected the conformation of
2
+
the macrocycle, which also affected binding with metal ions. Binding to Cu will likely require
rotation or conformational change of the two triazoles, BM35 and BM36 were able to adopt a
favorable conformation due to the more flexible three-methylene linkage at the anomeric center.
Table 3. Effect of the macrocycles on copper mediated click reaction of azide 14 with 1-octyne.
Condition A (1.0 mol%)
Condition B (5.0 mol%)
Entry Macrocycle Conversion Conversion Conversion Isolated yield
(
%) at 2 h
(%) at 6 h
(%) at 1 h
19
(%)
1
2
3
4
none
25
33
43
31
28
38
50
36
N/A
94
AM25
AM26
AM35
91, (100, 2 h)
100
91
86, (100, 2 h)
94
1
2
This article is protected by copyright. All rights reserved.

European Journal of Organic Chemistry
10.1002/ejoc.201801714
5
6
7
8
9
AM36
BM25
BM26
BM35
BM36
59
49
62
68
89
100
100
100
100
100
94
91
91
91
91
85
100
100
For both conditions: Sugar azide (1 equiv), CuSO4 5H
NaAsc (0.2 equiv). Condition A: 1.0 mol% macrocycle in EtOH/H
mol% macrocyle in t-BuOH/THF/H O (1: 1: 1).
2
O (0.1 equiv), 1-octyne (1.2 equiv),
2
O (1:1); Condition B: 5.0
2
Besides the sugar azide, we also screened a few other azides and found that two azido derivatives
participated in the cycloaddition reaction rather slowly when using CuSO and sodium ascorbate
4
as the catalyst; these include the tetraethylene glycol derived mono azide 17 and the meta acetyl
phenyl azide 19 (Figure 4). We found that the macrocycle BM35 was very effective in accelerating
the cycloaddition reactions. The click reaction of the aliphatic azide 17 with phenyl acetylene had
only 25% conversion at 1 h and 56% conversion at 12 h. However, in presence of 2.0 mol% of
BM35, the reaction was completed in 1 h with 100% conversion to the desired product. For the
phenyl azide 19, the reaction had only 15% conversion at 2 h and 21% conversion at 4 h; but with
the macrocycle ligand, with 2.5 mol% BM35 the reaction was completed in 4 h and with 5.0 mol%
BM35, the reaction had 100% conversion within 2 h.
1
3
This article is protected by copyright. All rights reserved.

European Journal of Organic Chemistry
10.1002/ejoc.201801714
Figure 4. The azides and click reaction products that were catalyzed using BM35.
Conclusions
In summary, using CuAAC as the key cyclization step we have synthesized a series of eight N-
acetyl-D-glucosamine based 18-20 membered ring macrocycles in synthetically useful yields and
quantities. The method to construct large glycomacrocycles from readily available starting
materials can be extended to the synthesis of other sugar-based macrocycles. The macrocycles
synthesized have shown significant rate acceleration for the CuSO mediated AACs of 2-
4
acetamido-2-deoxy--D-glucopyranosyl azide 3,4,6-triacetate 14 with alkynes in aqueous
mixtures. The benzoate protected macrocycles were more efficient than the acetate protected
compounds. For the click reaction of sugar azide with 1-octyne, the BM35 and BM36 were much
more efficient than the other macrocycles. Similar catalytic effects using BM35 were observed for
two other azides, which indicated the scope of the substrates was not limited to sugar azide. These
results clearly indicated that the macrocycles obtained in this study are effective ligands to
accelerate the copper sulfate mediated azide and alkyne cycloaddition reactions. The structure and
activity correlation can lead to more efficient ligand design for other copper catalyzed reactions.
Besides being useful for catalysis, these sugar-embedded macrocycles are expected to exhibit
1
4
This article is protected by copyright. All rights reserved.

European Journal of Organic Chemistry
10.1002/ejoc.201801714
interesting properties as natural product analogs and they may be useful for chiral recognition etc.
We are continuing with the study of these macrocycles for other applications and the results will
be reported in due course.
Experimental Section
The detailed synthetic procedures and characterization for all intermediates 7a-13D, the eight
macrocycles, and compounds 18 and 20 are included in the Supporting Information. The
1
experimental conditions and H NMR spectra using for reaction monitoring for all tables and
1
13
macrocycles AM25-BM36 are also provided in the Supporting information. Copies of H and C
NMR spectra for all intermediates, 2D-COSY and HSQC NMR spectra for macrocycles are
provided in SI. One example of the synthesis for AM25 is given below.
General procedure for the synthesis of macrocycles
To a 50 mL round bottom flask, macrocycle precursor (1 equiv), CuI (0.2 equiv) and DIEA (5
equiv) were mixed with CH CN as solvent (starting material/solvent = ~0.015 mmol/mL). The
3
reaction was stirred at 10 hours under 0 °C. Solvent was removed by the rotavap to afford the
crude, which was purified by column chromatography using eluent from pure DCM to 5% DCM
to afford desired macrocycles. Amount of all chemicals, yield, R
macrocycle are listed respectively.
f
value and characterization of the
Synthesis of compound AM25. Compound 12A (54 mg, 0.104 mmol, 1 equiv), CuI (3.8 mg,
.021 mmol, 0.2 equiv), DIEA (0.09 mL, 0.520 mmol, 5 equiv), CH CN (7 mL). Off-white solid
0
3
1
5
This article is protected by copyright. All rights reserved.

European Journal of Organic Chemistry
10.1002/ejoc.201801714
1
(22 mg, 41%) was obtained as the desired product (R
f
= 0.2 in 5% MeOH/DCM). H NMR (400
MHz, CDCl ) δ 7.42 (s, 1H, HC=C-), 7.31 (s, 1H, HC=C-), 5.77 (d, J = 9.4 Hz, 1H, -NH), 5.25
3
(dd, J = 10.7, 9.4 Hz, 1H, H-3), 5.06 (t, J = 9.4 Hz, 1H, H-4), 4.81 (d, J = 3.7 Hz, 1H, H-1), 4.72-
4
.63 (m, 1H, -O-CH
-CH
H), 2.09 (s, 3H), 2.07 (s, 3H), 2.00 (s, 3H), 1.86-1.65 (m, 3H), 1.65-1.51 (m, 1H), 1.32-1.19 (m,
2
-CH
a
-N), 4.52-4.22 (m, 5H, H-6
a
, H-2, -O-CH
2
-CH
b
-N, H-6
b
, H-5), 3.53-3.44
(m, 1H, -O-CH
a
2
-N), 3.40-3.32 (m, 1H, -O-CH
b
-CH -N), 2.92-2.73 (m, 3H), 2.68-2.57 (m,
2
1
1
3
2
5
1
3
H), 1.15-1.01 (m, 1H); C NMR (100 MHz, CDCl ) δ 171.2, 170.0, 169.8, 96.5 (C-1), 70.8 (C-
3
), 70.0 (C-4), 68.9 (C-5), 65.9 (-O-CH
2
-CH
2
-N), 51.7 (C-2), 51.3 (C-6), 48.5 (-O-CH
2
-CH
2
-N),
Na,
+
7.1, 26.7, 25.6, 24.6, 24.0, 23.1, 20.6. HRMS (ESI+) ([M + Na] ) m/z calcd for C23
42.2334, found 542.2330.
H
33
N
7
O
7
Acknowledgement
The work was supported by National Science Foundation grants CHE1313633 and CHE 1808609.
References cited:
1
2
3
4
5
6
.
.
.
.
.
.
E. Marsault, M. L. Peterson, J. Med. Chem. 2011, 54, 1961-2004.
E. M. Driggers, S. P. Hale, J. Lee, N. K. Terrett, Nat. Rev. Drug Discov. 2008, 7, 608-624.
X. Yu, D. Sun Molecules 2013, 18, 6230-6268.
D. Spring, S. Collins, S. Bartlett, F. Nie, H. Sore, Synthesis 2016, 48, 1457-1473
A. K. Yudin, Chem. Sci. 2015, 6, 30-49.
C. Shu, X. Zeng, M. H. Hao, X. Wei, N. K. Yee, C. A. Busacca, Z. Han, V. Farina, C. H.
Senanayake, Org. Lett. 2008, 10, 1303-1306.
1
6
This article is protected by copyright. All rights reserved.

European Journal of Organic Chemistry
10.1002/ejoc.201801714
7
8
9
.
.
.
Y. Shi, S. Challa, P. Sang, F. She, C. Li, G. M. Gray, A. Nimmagadda, P. Teng, T. Odom,
Y. Wang, A. van der Vaart, Q. Li, J. Cai, J. Med. Chem. 2017, 60, 9290-9298.
V. Marti-Centelles, M. D. Pandey, M. I. Burguete, S. V. Luis, Chem. Rev. 2015, 115, 8736-
8
834.
E. Oueis, M. Jaspars, N. J. Westwood, J. H. Naismith, Angew. Chem. Int. Ed. 2016, 55,
842-5845; Angew. Chem. 2016, 128, 5936-5939.
5
1
1
1
0.
1.
2.
J. Xie, N. Bogliotti, Chem. Rev. 2014, 114, 7678-7739.
A. Ignaczak, S. Porwanski, M. Szyszka, New J. Chem. 2017, 41, 521-529.
S. S. Arya Ajay, Munna Prasad Gupt, Vikas Bajpai, Hamidullah, Brijesh Kumar, Mahabir
Prasad Kaushik, R. P. Tripathi, Org. Lett. 2012, 14, 4306-4309.
1
1
3.
4.
A. Rathjens, J. Thiem, Carbohydr. Res. 2017, 438, 18-25.
V. V. Rostovtsev, L. G. Green, V. V. Fokin, K. B. Sharpless, Angew. Chem. Int. Ed. 2002,
4
1, 2596-2599; Angew. Chem. 2002, 114, 2708-2711.
M. Delbianco, P. Bharate, S. Varela-Aramburu, P. H. Seeberger, Chem. Rev. 2016, 116,
693-1752.
V. K. Tiwari, B. B. Mishra, K. B. Mishra, N. Mishra, A. S. Singh, X. Chen, Chem. Rev.
016, 116, 3086-3240.
1
1
5.
6.
1
2
1
1
1
7.
8.
9.
Y. M. Chabre, R. Roy, Chem. Soc. Rev. 2013, 42, 4657-4708.
C. Mueller, G. Despras, T. K. Lindhorst, Chem. Soc. Rev. 2016, 45, 3275-3302.
C. Ornelas, J. Ruiz Aranzaes, E. Cloutet, S. Alves, D. Astruc, Angew. Chem. Int. Ed. 2007,
4
6, 872-877; Angew. Chem. 2007, 119, 890-895.
A. Pathigoolla, R. G. Gonnade, K. M. Sureshan, Angew. Chem. Int. Ed. 2012, 51, 4362-
366; Angew. Chem. 2012, 124, 4438-4442.
2
0.
4
1
7
This article is protected by copyright. All rights reserved.

European Journal of Organic Chemistry
10.1002/ejoc.201801714
2
2
2
2
1.
2.
3.
4.
M. Juricek, P. H. J. Kouwer, A. E. Rowan, Chem. Commun. 2011, 47, 8740-8749.
A. A. Jafari, H. Mahmoudi, H. Firouzabadi, RSC Adv. 2015, 5, 107474-107481.
E. Haldon, M. C. Nicasio, P. J. Perez, Org. Biomol. Chem. 2015, 13, 9528-9550.
X. F. Gao, W. M. Sun, X. M. Li, X. J. Liu, L. S. Wang, Z. Liu, J. Guo, Catal. Commun.
2
016, 73, 103-108.
2
5.
C. Besanceney-Webler, H. Jiang, T. Zheng, L. Feng, D. Soriano del Amo, W. Wang, L. M.
Klivansky, F. L. Marlow, Y. Liu, P. Wu, Angew. Chem. Int. Ed. 2011, 50, 8051-8056;
Angew. Chem. 2011, 123, 8201-8206.
2
2
6.
7.
D. Soriano del Amo, W. Wang, H. Jiang, C. Besanceney, A. C. Yan, M. Levy, Y. Liu, F.
L. Marlow, P. Wu, J. Am. Chem. Soc. 2010, 132, 16893-16899.
S. I. Presolski, V. Hong, S. H. Cho, M. G. Finn, J. Am. Chem. Soc. 2010, 132, 14570-
1
4576.
2
2
8.
9.
P. Etayo, C. Ayats, M. A. Pericas, Chem. Commun. 2016, 52, 1997-2010.
C. Spiteri, J. E. Moses, Angew. Chem. Int. Ed. 2010, 49, 31-33; Angew. Chem. 2010, 122,
3
3-36.
3
3
3
3
3
3
0.
1.
2.
3.
4.
5.
S. Ozcubukcu, E. Ozkal, C. Jimeno, M. A. Pericas, Org. Lett. 2009, 11, 4680-4683.
D. Huang, P. Zhao, D. Astruc, Coord. Chem. Rev. 2014, 272, 145-165.
D. Pasini, Molecules 2013, 18, 9512-9530.
L. Xu, Y. Li, Y. Li, Asian J. Org. Chem. 2014, 3, 582-602.
A. Ghorai, S. Reddy K, B. Achari, P. Chattopadhyay, Org. Lett. 2014, 16, 3196-3199.
Y. Yu, N. Bogliotti, J. Tang, J. Xie, Eur. J. Org. Chem. 2013, 7749-7760.
1
8
This article is protected by copyright. All rights reserved.

European Journal of Organic Chemistry
10.1002/ejoc.201801714
3
6.
V. L. Campo, I. M. Ivanova, I. Carvalho, C. D. Lopes, Z. A. Carneiro, G. Saalbach, S.
Schenkman, J. S. da Silva, S. A. Nepogodiev, R. A. Field, Tetrahedron 2015, 71, 7344-
7
353.
M. L. Lepage, J. P. Schneider, A. Bodlenner, P. Compain, J. Org. Chem. 2015, 80, 10719-
0733.
3
3
3
4
7.
8.
9.
0.
1
S. Jogula, B. Dasari, M. Khatravath, G. Chandrasekar, S. S. Kitambi, P. Arya, Eur. J. Org.
Chem. 2013, 5036-5040.
S. Chandrasekhar, C. L. Rao, C. Nagesh, C. R. Reddy, B. Sridhar, Tetrahedron Lett. 2007,
4
8, 5869-5872.
V. L. Campo, I. Carvalho, C. H. T. P. Da Silva, S. Schenkman, L. Hill, S. A. Nepogodiev,
R. A. Field, Chem. Sci. 2010, 1, 507-514.
4
4
4
4
4
1.
2.
3.
4.
5.
S. Muthana, H. Yu, H. Cao, J. Cheng, X. Chen, J. Org. Chem. 2009, 74, 2928-2936.
A. Allam, L. Dupont, J. B. Behr, R. Plantier-Royon, Eur. J. Org. Chem. 2012, 817-823.
A. Singh, V. Khatri, S. Malhotra, A. K. Prasad, Carbohydr. Res. 2016, 421, 25-32.
A. Pathigoolla, K. M. Sureshan, Chem. Commun. 2014, 50, 317-319.
J. Zhou, M. Reidy, C. O'Reilly, D. V. Jarikote, A. Negi, A. Samali, E. Szegezdi, P. V.
Murphy, Org. Lett. 2015, 17, 1672-1675.
4
4
4
6.
7.
8.
G. Wang, A. Chen, H. P. R. Mangunuru, J. R. Yerabolu, RSC Adv. 2017, 7, 40887-40895.
H. P. R. Mangunuru, J. R. Yerabolu, D. Liu, G. Wang, Tetrahedron Lett. 2015, 56, 82-85.
H. P. R. Mangunuru, J. R. Yerabolu, G. Wang, Tetrahedron Lett. 2015, 56, 3361-3364.
1
9
This article is protected by copyright. All rights reserved.