Direct azidation of allylic/benzylic alcohols and ethers followed by the click reaction: One-pot synthesis of 1,2,3-triazoles and 1,2,3-triazole moiety embedded macrocycles

Article abstract of DOI:10.1016/j.tet.2015.06.099

Investigations on the one-pot direct azidation of allylic/benzylic alcohols or their methyl ethers followed by the click reaction are reported. Two methods involving sequential reactions were developed for synthesizing substituted 1,2,3-triazoles starting from allylic/benzylic alcohols. The first method involves magnetically separable nano Fe₃O₄-catalyzed direct azidation of various allylic/benzylic alcohols with TMSN₃ as the first step followed by the Cu-catalyzed click reaction of azides with alkynes as the second step. The second method involves Cu(OTf)₂-catalyzed direct azidation of allylic/benzylic alcohols and their methyl ethers with TMSN₃ as the first step followed by the click reaction of azides with alkynes as the second step. In this method, Cu(OTf)₂ served as a single catalyst for both the azidation of alcohol and click reaction steps. Utility of this protocol has been revealed by synthesizing new classes of polyether systems and macrocyles embedded with the 1,2,3-triazole and 1,3-diyne units.

Full text of DOI:10.1016/j.tet.2015.06.099

Accepted Manuscript
Direct Azidation of Allylic/Benzylic Alcohols and Ethers Followed by the Click
Reaction: One-Pot Synthesis of 1,2,3-Triazoles and 1,2,3-Triazole Moiety Embedded
Macrocycles
Naveen Srinivasarao, Arulananda Babu, Nayyar Ahmad Aslam, Akshey Sandhu,
Dharmendra Kumar Singh, Ameet Rana
PII:
S0040-4020(15)00996-5
10.1016/j.tet.2015.06.099
TET 26935
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 21 March 2015
Revised Date: 8 June 2015
Accepted Date: 29 June 2015
Please cite this article as: Srinivasarao N, Babu A, Aslam NA, Sandhu A, Singh DK, Rana A, Direct
Azidation of Allylic/Benzylic Alcohols and Ethers Followed by the Click Reaction: One-Pot Synthesis of
1,2,3-Triazoles and 1,2,3-Triazole Moiety Embedded Macrocycles, Tetrahedron (2015), doi: 10.1016/
j.tet.2015.06.099.
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Direct Azidation of Allylic/Benzylic Alcohols
and Ethers Followed by the Click Reaction:
One-Pot Synthesis of 1,2,3-Triazoles and
Leave this area blank for abstract info.
1,2,3-Triazole Moiety Embedded
Macrocycles
Naveen, Srinivasarao Arulananda Babu,* Nayyar Ahmad Aslam, Akshey Sandhu, Dharmendra Kumar Singh and
Ameet Rana
Department of Chemical Sciences, Indian Institute of Science Education and Research (IISER) Mohali, Knowledge City, Sector 81, SAS
Nagar, Mohali, Manauli P.O., Punjab, 140306, India

1
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Tetrahedron
journal homepage: www.elsevier.com
Direct Azidation of Allylic/Benzylic Alcohols and Ethers Followed by the Click Reaction:
One-Pot Synthesis of 1,2,3-Triazoles and 1,2,3-Triazole Moiety Embedded Macrocycles
Naveen, Srinivasarao Arulananda Babu∗ Nayyar Ahmad Aslam, Akshey Sandhu, Dharmendra Kumar
Singh and Ameet Rana
a
Department of Chemical Sciences, Indian Institute of Science Education and Research (IISER) Mohali, Knowledge City, Sector 81, SAS Nagar, Mohali,
Manauli P.O., Punjab, 140306, India
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
Investigations on the one-pot direct azidation of allylic/benzylic alcohols or their methyl ethers
followed by the click reaction are reported. Two methods involving sequential reactions were
developed for synthesizing substituted 1,2,3 triazoles starting from allylic/benzylic alcohols. The
first method involves magnetically separable nano Fe
allylic/benzylic alcohols with TMSN as the first step followed by the Cu-catalyzed click
reaction of azides with alkynes as the second step. The second method involves Cu(OTf)
catalyzed direct azidation of allylic/benzylic alcohols and their methyl ethers with TMSN as the
first step followed by the click reaction of azides with alkynes as the second step. In this method,
Cu(OTf) served as a single catalyst for both the azidation of alcohol and click reaction steps.
3 4
O -catalylzed direct azidation of various
Available online
3
2
–
Keywords:
3
Allylic/benzylic alcohols
click reaction
cycloaddition
magnetite
2
Utility of this protocol has been revealed by synthesizing new classes of polyether systems and
macrocyles embedded with the 1,2,3-triazole and 1,3-diyne units.
triazoles
macrocycles
2
009 Elsevier Ltd. All rights reserved.
Catalytic direct nucleophilic substitution of free OH group of
allylic/benzylic alcohols by nucleophiles is an important process
conversion of alcohols into azides has been accomplished using
the well-established Mitsunobu reaction pathway and modified
1-3
14,15
in organic chemistry. In spite of the two known limitations,
such as the poor ability of the OH group as a leaving group and
the formation water as the by-product which requires the use of a
water tolerant catalyst, several procedures involving a range of
catalysts (e.g., transition metal, Brønsted acid, Lewis acid
catalysts) were developed for the direct nucleophilic substitution
of allylic/benzylic alcohols by various carbon-based or nitrogen-
based nucleophiles. Consequently, the formation of carbon-
nitrogen bonds via the direct catalytic substitution of OH group
of alcohols with nitrogen-based nucleophiles is a simple synthetic
procedure for obtaining allylic/benzylic amines and azides and
Mitsunobu-type procedures.
Along this line, there have been
other methods for the direct conversion of alcohols into azides,
5
c
16a
which
TsIm/TBAI/NaN3,
include,1
NaN /BF ·OEt ,
NaN /CCl -DMF,
3
3
2
3 4
6b
16c
2,4,6-trichloro[1,3,5]triazine/n-Bu NN ,
4
3
2-azido-1,3 dimethylimidazolinium hexafluorophosphate (2-
6
a
16d
ADMP)/DBU
NaN /amphiphilic
and NaN /ionic liquid [H-NMP]HSO4,
3
resin-supported
palladium
phosphine
3
16e
6b
complex and NaN /triphosgene. On the other hand, the direct
3
azidation of allylic and benzylic alcohols with TMSN3 as an
azide reagent has been accomplished in the presence of various
17a
6
c
catalysts/promoters, e.g., AgOTf,
Mo(IV) complex,
4-11
17b
17c
4c
other related nitrogenous compounds.
Several allylic/benzylic
Cu(ClO ) ·6H O,
Cu(OTf)2
and BF ·OEt . Further, the
4
2
2
3 2
amines and azides are versatile synthetic building blocks for
synthesizing heterocyclic compounds, natural products and
conversion of allyl esters into azides has been carried out in the
presence of Pd(0) catalyst.
18
4
-11
biologically active molecules.
Notably, the azide moiety is
The synthesis of 1,2,3-triazoles via the [3+2] cycloaddition of
organic azides and alkynes (click reaction) has gained significant
attention in the fields of chemistry, biology, medicine, and
reported to be a key component of the HIV/AIDS drug,
12
zidovudine.
10,11
Conversion of readily accessible alcohols to azides is a
straightforward method for the synthesis of a variety of organic
azides. Usually, this transformation has been carried out in two
steps; first an alcohol is converted in to the respective halide or
sulfonate and then, the corresponding halide/sulfonate is
converted into an azide via the nucleophilic substitution
materials science.
Generally, the required organic azide
molecules are prepared by the substitution reaction of the organic
halides/pseudo halides by sodium azide. It is worth to mention
that some of the organic azide molecules can be explosive and it
is essential to handle the organic azides with care. Hence, a one-
pot synthesis of organic azide followed by the click reaction
procedure without isolating the corresponding azide would be
13
reaction. Consequently, the direct azidation of allylic/benzylic
alcohols with an azide reagent is considered as one of the easy
ways for synthesizing allylic/benzylic azides. The direct
19,20
very convenient.
Accordingly, the one-pot synthesis of 1,2,3-
triazoles involving sequential reactions starting from organic
—
——
∗
Corresponding author. Tel.: +91-172-2293165; fax: +91-172-2240266; e-mail: sababu@iisermohali.ac.in

2
Tetrahedron
halide/pseudo halide, azide reagent and a
A
lky
C
neCEha
P
veTEbe
D
en MAet
NU
hers
S
di
C
d n
R
otIPre
T
act with TMSN in the presence of nano Fe O
3
3
4
19-21
reported.
and subsequently, the click reaction also failed to afford the
corresponding 1,2,3-triazole (Scheme 1).
Scheme 1: Theme of this work. One-pot direct azidation of allylic/benzylic alcohols and ethers followed by the
click reaction.
We envisaged to overcome this limitation and simplify the
In this one-pot process, if we can use readily accessible
starting materials, e.g., alcohols instead of organic halides/pseudo
halides or protected alcohols, then the synthetic procedure will be
simple to work out. Although, methods for the direct conversion
of alcohols into azides are well-known; however, to the best of
our knowledge, one-pot sequential processes comprising, the
direct azidation of allylic/benzylic alcohols followed by the Cu-
catalyzed click reaction of the corresponding azides with alkynes
reaction procedure using a single catalyst to perform the direct
azidation of allylic/benzylic alcohols with TMSN followed by
3
the click reaction of the corresponding azides with alkynes. In
view of developing synthetic procedures which are simple to
work out and for achieving the chemical diversity, we envisioned
23
to improve our method and use of Cu(OTf) a single catalyst for
2
performing the one-pot direct azidation of allylic/benzylic
alcohols with TMSN and click reaction of the corresponding
3
20
are limited and not been well explored. Wang et al. revealed a
azides with alkynes (Scheme 1). Herein, we report our
comprehensive works on the synthesis of several substituted
1,2,3-triazole via the one-pot direct azidation of allylic
alcohols/ethers followed by the click reaction. Further, this
protocol has been applied for the synthesis of acyclic and
macrocyclic crown ethers/polyethers embedded with bis-triazole
moieties and a 1,3-diyne unit, starting from bis-homoallylic
alcohols and involving the Glaser-Eglinton-Hay coupling
reaction.
one-pot multistep synthesis of triazolylglycosides from
4d
unprotected monosaccharides. Sreedhar et al. revealed a one-
pot sequential reaction procedure for the synthesis of 1,2,3-
triazoles from homoallyl alcohols via the Pd-catalyzed azidation
followed by the Cu(I)-catalyzed click reaction. Apart from this
21a
21b
21c
work, Fukuzawa, Chandrasekhar, Sreedhar, have revealed
the one-pot sequential reaction procedures for the synthesis of
1
,2,3-triazoles starting from benzyl acetates or Baylis–Hillman
22
acetates. Yadav et al. reported a four-component reaction of
aldehyde, alcohol, azide, and alkyne via Cu(OTf) -catalyzed
Scheme 1 illustrates the two different methods (method A and
method B) presented in this paper for synthesizing several
substituted 1,2,3 triazole derivatives starting from allylic and
benzylic alcohols without isolating the corresponding azides. To
accomplish the method A, initially, we performed various
optimization reactions to find out the suitable reaction condition
2
acetal formation followed by Cu(0)-mediated click reaction.
23
Recently, we also reported our preliminary work encompassing
the direct azidation of allylic/benzylic alcohols catalyzed by
24
magnetic nano Fe O4 followed by the Cu-catalyzed click
3
reaction of the corresponding azides with alkynes for the
synthesis of 1,2,3-triazoles (Scheme 1). This method involves
magnetically separable nano Fe O -catalyzed direct azidation of
for the direct azidation of allylic alcohol 1a with TMSN in the
3
2
4-26
presence of magnetically separable nano Fe O4 catalyst
3
4
3
various allylic/benzylic alcohols with TMSN as the first step
(particle size = < 50 nm). We found two best reaction conditions
for the effective conversion of alcohol 1a into the corresponding
azide substrate 2. We obtained the azide substrate 2 in 89% yield
when the azidation of 1a (1 equiv) was carried out with TMSN3
3
followed by the Cu-catalyzed click reaction of the corresponding
azides with alkynes as the second step. Further, we found some
limitations with this method that some of the alcohols/methyl

3
(
2.5 equiv) in the presence of 15 mol% of nano
at rt (entry 2, Table 1). The azide substrate 2 was obtained in
8% yield when the azidation of 1a (1 equiv) was carried out
with TMSN3 (2.5 equiv) in the presence of nano Fe O (15
A
Fe
C
O
C
in
E
P
1,
T
2-D
ED MANUSCRIPT
C
E
3
4
Table 1. Nano Fe O -catalyzed reaction 1a with TMSN .
3 4
3
9
3
4
o
mol%) in 1,2-DCE at 70 C (entry 5, Table 1). As shown in the
Table 1, the conversion of alcohol 1a into the corresponding
azide substrate 2 was not effective when the reaction was carried
out in solvents, such as 1,4-dioxane, MeCN, MeOH, acetone,
THF and toluene and in the presence of other catalysts, e.g. nano
Fe O or powder Fe O . We have also checked the recyclability
Entry Catalyst
mol %)
Solvent
(1.5 mL)
Reaction
Condition
Yield of
azide 2 (%)
(
2
3
3
4
of the magnetic nano Fe O catalyst and accordingly, the direct
o
3
4
1
2
3
4
5
6
7
8
9
1
1
1
1
1
nil
1,2-DCE
1,2-DCE
1,2-DCE
1,2-DCE
1,2-DCE
1,2-DCE
1,2-DCE
DCM
70 C, 40 h
0
89
80
83
98
85
89
85
92
0
0
0
23
20
55
92
<5
35
azidation of allylic alcohol 1a with TMSN afforded the product
nano Fe O (15)
rt, 15 h
rt, 15 h
rt, 15 h
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
2
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
3
th
a
2
in 95% yield in the 7 run (Table 1). The recovered nano Fe O
nano Fe
nano Fe
nano Fe
nano Fe
nano Fe
nano Fe
nano Fe
nano Fe
nano Fe
nano Fe
nano Fe
nano Fe
nano Fe
nano Fe
nano Fe
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
(15)
(15)
(15)
(15)
(15)
(15)
(15)
(15)
(15)
(15)
(15)
(15)
(15)
(10)
(15)
3
4
b
catalyst after the usage at different runs was analyzed by FT-IR
and HRTEM. The FT-IR spectra of the fresh and recovered
magnetic nano Fe O catalyst showed no characteristic changes
o
70 C, 6 h
o
a
70 C, 6 h
o
b
3
4
70 C, 6 h
and the HRTEM analysis of the recovered magnetic nano Fe O
3
4
rt, 10 h
reflux, 8 h
catalyst revealed that there was no significant change in the
DCM
23
0
1
2
3
4
1,4-dioxane rt, 30 h
morphology of the nanoparticles.
MeCN
MeOH
acetone
THF
toluene
1,2-DCE
1,2-DCE
rt, 30 h
rt, 30 h
rt, 30 h
rt, 30 h
rt, 30 h
Next, we focused our attention to execute the one-pot method
A and method B to synthesize substituted 1,2,3 triazole
derivatives starting from allylic and benzylic alcohols. Having
the best reaction condition for the direct azidation of 1a with
TMSN in the presence of nano Fe O catalyst (entry 5, Table 1),
15
o
1
1
1
6
7
8
70 C, 16 h
o
70 C, 30 h
3
3
4
o
powder Fe
3
O
4
(15) 1,2-DCE
70 C, 48 h
then, we decided to perform the Cu-catalyzed click reaction of
the product 2 in the same RB without isolating the azide substrate
c
Recycling of nano Fe O
3
4
2
. Accordingly, at first, we carried out the method A procedure,
Run
1
2
6
97
3
8
97
4
10
97
5
12
97
6
15
96
7
20
95
in which the direct azidation of allylic alcohol 1a was performed
followed by the copper-catalyzed click reaction of the azide 2
Time (h)
6
Yield of 2 (%)
a
98
b
((E)-(3-azidoprop-1-ene-1,3-diyl)dibenzene)
with
ethyl
In this case, 0.55 mmol of TMSN was used. In this case, 0.75 mmol of
3
c
propiolate which gave the substituted 1,2,3-triazole derivative 4a
in 86% yield (entry 1, method A, Table 2). Successively, we
performed the one-pot direct azidation of substrate 1a followed
by the copper-catalyzed click reaction of the product 2 with
various alkynes 3b-e, 3g-j, which gave the corresponding
substituted 1,2,3-triazole derivatives 4b-e, 4g-j in 75-93% yields
TMSN3 was used. The reaction was carried out using 1a (0.5 mmol),
TMSN (1.25 mmol) and nano Fe O (15 mol%) in 1,2-DCE (1.5 mL) at 70
3
3
4
o
C.
Next, we decided to explore the direct conversion of various
allylic alcohols 1b-g (Table 3) into the corresponding substituted
1,2,3-triazole derivatives in one-pot using either method A or
method B procedure. The substituted 1,2,3-triazole derivatives 4k
(75%) and 4l (60%) were synthesized from 1b using the method
(method A, Table 2).
Method A involves nano Fe O -catalyzed direct azidation of
3
4
1
a with TMSN as the first step followed by the Cu-catalyzed
B procedure involving Cu(OTf) as the single catalyst (entries 1
3
2
click reaction of the corresponding azides with alkynes as the
second step. We envisaged simplifying the reaction procedure of
the method A and using a single catalyst to perform the direct
and 2, Table 3). The substituted 1,2,3-triazole derivatives 4m-o
and 4oA were synthesized from the corresponding alcohols 1b-d
and 1dA using the method A or B procedures (entries 3-6, Table
3). The products 4n,o and 4oA were obtained as a mixture of
regioisomers since the corresponding allylic alcohols 1c,d and
1dA underwent an allylic rearrangement under the experimental
condition, thereby led to the formation of the corresponding
rigioisomers. The allylic alcohols 1e-g failed to afford
corresponding substituted 1,2,3-triazole derivatives 4p and 4q
when the direct azidation of allylic alcohols 1e-g followed by the
click reaction was performed using method A procedure. This is
because the nano Fe O -catalyzded conversion of allylic alcohols
1e-g into the corresponding azides did not occur in the first step
as a result the subsequent click reaction failed to afford the 1,2,3-
triazole derivatives 4p and 4q under the method A procedure
(entries 6-8, method A, Table 3). However, the allylic alcohols
1e-g successfully afforded the corresponding substituted 1,2,3-
triazole derivatives 4p (70-80%) and 4q (76%) when the direct
azidation of allylic alcohols 1e-g followed by the click reaction
was performed using the method B procedure (entries 7-10,
method B, Table 3). Similarly, the substituted 1,2,3-triazole
derivatives 4r was obtained in 85% yield from the corresponding
alcohols 1g using the method B procedure (entry 9, method B
Table 3).
azidation of 1a with TMSN followed by the click reaction of the
3
corresponding azides with alkynes. Accordingly, we used the
method B procedure, in which the direct azidation of substrate 1a
with TMSN3 was carried out in the presence of 5 mol% of
Cu(OTf) followed by the click reaction of the product 2 in the
2
same RB with various alkynes. In this regard, initially, we
performed the optimization of the reactions to find out the best
reaction conditions for the method B. The direct azidation of the
substrate 1a with TMSN in the presence of 5 mol% of Cu(OTf)2
3
3
4
followed by the click reaction of the azide 2 with 3a and without
any additive in the click reaction step did not give the expected
1
,2,3-triazole 4a (entry 1, method B, Table 2). When we used
DIPEA or L-ascorbic acid as an additive, the 1,2,3-triazole 4a
was obtained in 10 and 20% yields, respectively (entry 1, method
B, Table 2). The use of sodium L-ascorbate as an additive in the
click reaction step gave the 1,2,3-triazole 4a in 87% yield (entry
1
, method B, Table 2). Then, using the same reaction conditions,
we performed the direct azidation of substrate 1a followed by the
click reaction of the product 2 with various alkynes 3b-i, which
gave the corresponding substituted 1,2,3-triazole derivatives 4b-i
in 72-98% yields (method B, Table 2).

4
Tetrahedron
ACCEPTED MANUSCRIPT
Table 2. One-Pot direct azidation of allylic alcohol 1a followed by the click reaction with 4a-j. Synthesis of
a
substituted 1,2,3-triazoles 4a-j.
method A:
CuSO 5H O (30 mol%)
4
2
Ph
4
Ph
Y
magetically separable
nano Fe O (15 mol%)
sodium L-ascorbate (30 mol%)
Ph
aOH
3
4
Ph
N
N
1
X
+
1
6
,2-DCE (1.5 mL)
alkyne (1.2 mmol)
THF / H2O (3 mL / 3 mL), rt, 12 h
N
TMSN3
o
h, 70 C
method B:
Ph
Ph
Y
Cu(OTf) (5 mol%)
sodium L-ascorbate (50 mol%)
Ph
aOH
2
Ph
N
N
1
X
+
DCM (3 mL)
3 h, rt
alkyne (1.25 mmol)
N
TMSN3
4
THF / H O (2 mL / 2 mL), rt, 20 h
2
Entry
Alkyne
Triazole
Yield (%)
Method A
Yield (%)
Method B
Ph
N
b
c
d
g
EtOOC
(0), (10), (20),
1
2
Ph
Ph
86
82
3
a
COOEt
e
f
(
60), (81), (87)
N
N
4
a
Ph
N
HO
Ph
O
75
97
3
b
N
N
4
OH
Ph
b
Ph
Ph
N
N
2
3
90
93
3
c
N4
c
Ph
O
Ph
N
O
96
72
N
N
O
4d
3
d
e
Ph
COOMe
MeOOC
COOMe
4
5
Ph
N
86
COOMe
3
N
N
4
e
Ph
Ph
Ph
Ph
Ph
Ph
N
N
-h
98
3
f
N
4f
N
N
6
7
85
92
97
93
3
g
h
N
g
4
N
N
3
N
4
h
Ph
CHO
O
OHC
O
Ph
N
N
8
9
85
75
89
N
3
i
4i
O
O
O
O
O
O
O
N
N
3
j
-h
N
N
N
N
O
Ph
Ph
Ph
Ph
4j
a
In method A, 0.5 mmol of 1a and 1.5 mmol of TMSN
3
were used. In method B, 0.5 mmol of 1a and 0.75 mmol of TMSN
3
were used.
In both the methods, initially, the azidation of 1a was carried out with TMSN
3
and after the reaction period the solvent was evaporated.
Then, the click reaction was carried out.
b
The reaction was carried out without sodium L-ascorbate.
DIPEA (50 mol%) was used instead of sodium L-ascorbate.
L-Ascorbic acid (50 mol%) was used instead of sodium L-ascorbate.
CuCl (60 mol%) was used instead of sodium L-ascorbate.
Sodium L-ascorbate (30 mol%) was used.
Sodium L-ascorbate (50 mol%) was used.
The reaction was not performed.
c
d
e
f
g
h

5
ACCEPTED MANUSCRIPT
Table 3. One-Pot direct azidation of various allylic alcohols 1b-g followed by the click reaction with alkynes.
a
Synthesis of substituted 1,2,3-triazoles 4k-r and 4oA.
a
In both the methods, initially, the azidation of 1a was carried out with TMSN
3
and after the reaction period the solvent was evaporated.
Then, the click reaction was carried out.
b
In method B, for all the reactions, 0.5 mmol of 1a and 0.75 mmol of TMSN
The reaction was not performed.
3
were used.
c
d
In this reaction, 1 mmol of alcohol and 3 mmol of TMSN
3
were used and the reaction time indicated in the parenthesis corresponds to
azidation reaction.
e
Products were obtained as a mixture of regioisomers due to an allylic rearrangement under the experimental condition.

6
Tetrahedron
ACCEPTED MANUSCRIPT
Table 4. One-Pot direct azidation of conjugated and cyclic allylic alcohols 1h-k followed by the click reaction
with alkynes. Synthesis of substituted 1,2,3-triazoles 4s-y.
CuSO 5H O (30 mol%)
method A:
4
2
Ph
magetically separable
nano Fe O (15 mol%)
Y
sodium L-ascorbate (30 mol%)
alcohol
+
3
4
Ph
Ph
N
N
X
1
,2-DCE (3 mL)
alkyne (2 mmol)
THF / H2O (3 mL / 3 mL), rt, 12 h
N
TMSN3
4
o
t (h), 70 C
method B:
Ph
Y
sodium L-ascorbate (50 mol%)
alcohol
+
TMSN3
Cu(OTf) (5 mol%)
2
N
N
X
DCM (3 mL)
alkyne (1.25 mmol)
N
4
3
h, rt
THF / H O (2 mL / 2 mL), rt, 20 h
2
Entry
1
Alcohol
Alkyne
Triazole
Yield (%) Yield (%)
Method A
Method Bb
Ph
Ph
N
N
Ph 62 (18 h)c 68
OH
Ph
N
4s
1h
3
c
Ph
N
N
COOEt
-d
2
3
1h
73
COOEt
N
4t
3
a
OHC
O
CHO
N
57 (18 h)c 42
1h
O
N
4u
N
3i
Ph
Ph
COOEt
N
OH
N
4
5
COOEt
N
N
62 (30 h)c
(76:24)e
<5f
Ph
Ph
Ph
Ph
3
3
a
Ph
Ph
Ph
4
1
i
v
COOEt
N
OH
N
45 (24 h)c
<5f
COOEt
(
88:12)e
Ph
1j
a
4
w
CH3
CH3
OH
6
7
COOEt
N
N
0
80
COOEt
3a
(24 h)c
(86:14)g
CH3
N
4x
CH3
1
k (60:40)
CH3
N
N
-d
87
(86:14)g
1
k (60:40)
CH3
N
3g
4y
a
In both the methods, initially, the azidation of 1a was carried out with TMSN
3
and after the reaction period the solvent was evaporated.
Then, the click reaction was carried out.
b
In method B, for all the reactions, 0.5 mmol of 1a and 0.75 mmol of TMSN
3
were used.
c
3
In this reaction, 1 mmol of alcohol and 3 mmol of TMSN were used and the reaction time indicated in the parenthesis corresponds to
azidation reaction.
d
The reaction was not performed.
e
Products were obtained as a mixture of regioisomers due to an allylic rearrangement under the experimental condition.
In this case, the reaction gave a mixture of compounds and the expected product could not be isolated in pure form.
The products 4x,y were obtained as a mixture of diastereomers as the starting material 1k was used as diastereomers
f
g

7
ACCEPTED MANUSCRIPT
Table 5. One-pot synthesis of 1,2,3-triazoles 6a-f and 4a,q,x from allylic and benzylic ethers 5a-
k.
a,b
Entry
Ether Substrate
Triazole
COOEt
Yield (%) Yield (%)
Method A Method B
OH
N
N
-d
5
a
1
2
Ph
Ph
Ph
N
6a
6a
71
Ph
Ph
OMe
Ph
5b
0
75
COOEt
N
N
OH
CH3
N
-d
3
4
5c
6b
35
-d
Ph
Ph
CH3
OMe
CH3
50
5d
6b
COOEt
N
N
OH
N
5
e
-d
5
6
6c
70
-d
OMe
5f
6c
70
COOEt
N
OH
N
N
-d
7
5g
52
70
6
d
N
N
OH
N
8c
-d
6e
5e
COOEt
CH3
N
OMe CH3
N
N
9
-d
87
80
5
h
6
f
Ph
Ph
10
0
Ph
N
Ph
OMe
COOEt
5
i
N
N
4a
CH3
CH3
OMe
N
N
COOEt -d
1
1
2
72
70
5
j
N
4
q
CH3
CH3
1
H3C
H3C
N
N
COOEt -d
OMe
(
84:16)e
5
(
k
N
4
x
60:40 )
a
Reaction condition for method A: The reaction was performed using 5 (1 mmol), TMSN
15 mol%) in 1,2-DCE (3 mL) at 70 C for 14-20 h and the solvent was evaporated and then, the click reaction was
3
(3 mmol) and nano Fe
3 4
O
o
(
4 2
carried out using ethyl propiolate (3a, 2 mmol) in THF (3 mL) and water (3 mL) in the presence of CuSO ·5H O (30
mol%) and sodium L-ascorbate (30 mol%) at rt for 12 h.
b
Reaction condition for method B: The reaction was performed using 5 (0.5 mmol), TMSN
3
(0.75 mmol) and
Cu(OTf)
2
(5 mol%) in DCM (3 mL) at rt for 3 h and the solvent was evaporated and then, the click reaction was carried
out using ethyl propiolate (3a, 1.25 mmol) in THF (2 mL) and water (2 mL) in the presence sodium L-ascorbate (50
mol%) at rt for 20 h.
c
In this case, alkyne 3g was used instead of 3a.
The reaction was not performed.
Product was obtained as a mixture of diastereomers as the starting material 5k was used as diastereomers.
d
e

8
Tetrahedron
Next, we performed the conversion of th
A
e
C
co
C
nju
E
g
P
at
T
ed
E
a
D
nd MA4a
N
(80
U
S
%
C
),
R
4
I
q (72%), and 4x (70%, dr 84:16, entries 10-12,
P
T
cyclic allylic alcohols 1h-k (Table 4) into the corresponding
substituted 1,2,3-triazole derivatives using the reaction conditions
of either method A or method B. The direct azidation of the
allylic alcohol 1h followed by the click reaction with 3c using the
method A and method B procedures afforded the substituted
Table 5).
Table 6. Cu(OTf) -catalyzed one-pot synthesis of bis-1,2,3-
2
1
,2,3-triazole derivative 4s in 62 and 68% yields, respectively.
triazoles 8a-e from bis-homoallyl alcohols.
The azidation of the allylic alcohol 1h followed by the click
reaction with different alkynes 3a and 3i afforded the
corresponding 1,2,3-triazole derivatives 4t (73% yield in method
B) and 4u (57% yield in method A). Then, the substituted 1,2,3-
triazole derivatives 4v (62%), and 4w (45%) were synthesized
from the corresponding cyclic allylic alcohols 1i and 1j using the
method A procedure (entries 4 and 5, Table 4). The products 4v
and 4w were obtained as a mixture of regioisomers since the
corresponding cyclic allylic alcohols 1i and 1j underwent an
allylic rearrangement under the experimental condition, thereby
led to the formation of their rigioisomers, respectively.
R
N
R
N
one-pot sequential
reactions
OH
HO
N
N
N
O
N
O
O
O
1. Cu(OTf)2, TMSN3
Linker
2
. L-sodium ascorbate
Linker
alkyne
7
(0.25 mmol)
8
Entry
Bis-Homoallyl Alcohol
Alkyne
Triazole System 8: Yield (%)
Et
Et
N
O
O
O
O
OH
HO
N
N
N
N
O
N
O
O
O
1
The cyclic allylic alcohol 1k failed to afford corresponding
substituted 1,2,3-triazole derivative 4x when the direct azidation
of allylic alcohol 1k followed by the click reaction with 3a was
performed using the method A procedure. This is perhaps,
because the nano Fe O -catalyzed conversion of allylic alcohol
3a
7a
8a; 72
Et
Et
3
4
O
O
OO
1
k into the corresponding azides did not occur in the first step
and as a result, the subsequent click reaction failed to afford the
,2,3-triazole derivative 4x (entry 6, method A, Table 4).
OH
HO
N
N
N
N
N
N
O
1
O
O
O
2
O
O
However, the cyclic allylic alcohol 1k successfully afforded the
corresponding substituted 1,2,3-triazole derivatives 4x (80%)
when the direct azidation of allylic alcohol 1k followed by the
click reaction was performed using the method B procedure
3a
7
b
8b; 84
Et
Et
O
O
O
O
(
entry 6, method B, Table 4). Similarly, the substituted 1,2,3-
OH
O
HO
triazole derivatives 4y (87%) was obtained from the alcohol 1k
using the method B procedure (entry 7, method B Table 4).
Since, we used the alcohol 1k as a mixture of diastereomers (dr
N
N
N
N
N
O
N
O
O
O
O
3
3a
O
O
6
4
0:40), the corresponding substituted 1,2,3-triazole derivatives
x and 4y were obtained as diastereomers with improved
7c
8
c; 82
Et
Et
diastereoselectivity (dr 86:14) under the experimental condition.
Our efforts to isolate the respective major isomers of 4x and 4y
were failed and the stereochemistry of the major/minor
diastereomers was not determined.
O
O
O
O
N
N
OH
HO
N
N
N
N
4
5
O
O
O
O
Next, we studied the direct conversion of the benzylic
alcohols 5a,c,e,g and methyl ethers 5b,d,f,h prepared from their
corresponding alcohols (Table 5) into the corresponding
substituted 1,2,3-triazole derivatives using the reaction conditions
of either method A or method B. The direct azidation of the
benzylic alcohol 5a followed by the click reaction with 3a using
the method A procedure afforded the substituted 1,2,3-triazole
derivative 6a in 71% yield (entry 1, method A, Table 5). On the
other hand, the direct azidation of the ether 5b followed by the
click reaction with 3a using the method A procedure failed to
afford the substituted 1,2,3-triazole derivative 6a (entry 2,
method A, Table 5). However, the direct azidation of the
substrate 5b followed by the click reaction with 3a using the
method B procedure successfully afforded the product 6a in 75%
yield (entry 2, method B, Table 5). Similarly, various substituted
3
a
8
d; 87
7d
CHO
OHC
O
O
OH
HO
N
N
N
N
N
N
O
O
O
O
3i
7a
8e; 68
a
Reagents and Conditions: The direct azidation of substrate 7 was carried
(10 mol%), TMSN (3 equiv) in DCM (3 mL) at rt for 3 h
out using Cu(OTf)
2
3
and the solvent was evaporated in vacuum. Then, the click reaction was
carried out using alkyne (5 equiv) in THF (2 mL) and water (2 mL) in the
presence of L-sodium ascorbate (100 mol%) at rt for 20 h.
1
,2,3-triazole derivatives 6b-f were synthesized in 35-87% yields
starting from the corresponding benzylic alcohols or their
corresponding methyl ethers 5b-h by using the method A and
method B procedures, respectively (entries 3-9, Table 5).
Additionally, the azidation of methyl ethers 5i-k prepared from
of their corresponding allyl alcohols followed by the click
reaction with ethyl propiolate under the method B procedure
successfully afforded the corresponding 1,2,3-triazole derivatives

9
ACCEPTED MANUSCRIPT
Ph
Me
Ph
Ph
I
N
N
N
Me
MeI
Me
+
N
N
N
N
I
+
N
I
reflux
N
Me
I
5
d
Ph
Ar
Ph
Ar
9
Ph
Ar
10; 85%
4o
Ar= p-Tolyl
Ph
Me
Ph
I
Ph H2 (1 atm)
N
MeI
N
N
Pd/C (10 mol%)
N
+
N
N
N
reflux
N
N
THF (2 mL)
4
d
Ph
Ph
24 h
Ph
Ph
Ph
Ph
4c
11; 91%
12; 92%
Ph
Ph
H (1 atm), Pd/C (10 mol%)
2
Ph
N3
Ph
1
NH2
3; 50%
2
THF (2 mL), rt, 24 h
(
1 mmol)
Scheme 2. Synthetic transformations of 1,2,3-triazole derivative 4c and conversion of azide 2 into 13.
a
Table 7. Assembling of bis-1,2,3-triazole incorporated polyether systems 8, 14 and 15
.
O
O
HO
O
O
OH
O
O
O
O
O
O
one-pot sequential
reactions
OH
HO
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
O
N
N
O
O
1. Cu(OTf)2, TMSN3
(a)
(b)
O
O
O
O
O
Linker
2. L-sodium ascorbate
alkyne (3i)
Linker
Linker
Linker
7
8
15
Triazole System 15: Yield (%)
14
Entry
Bis-Homoallyl Alcohol 7
Triazole System 8: Yield (%)
Triazole System 14: Yield (%)
O
O
OH
O
HO
O
O
O
O
O
O
O
1
N
N
OH
HO
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
O
O
O
O
O
O
O
O
O
O
O
O
7b
8f; 78
15a; 60
14a; 96
O
O
OH
O
HO
O
O
O
O
O
O
O
OH
O
HO
O
N
N
N
N
N
N
N
N
N
O
N
N
N
N
N
N
O
N
O
2
N
O
N
O
O
O
O
O
O
O
O
O
O
7c
14b; 95
15b; 85
8g; 81
O
O
HO
O
OH
O
O
O
O
O
O
O
OH
HO
N
N
N
N
N
N
N
N
N
N
N
N
N
O
N
N
N
N
N
O
O
3
O
O
O
O
O
7d
8h; 78
14c; 92
15c; 80
a
2 3
Reagents and Conditions: The direct azidation of substrate 7 was carried out using Cu(OTf) (10 mol%), TMSN (3 equiv) in DCM (3 mL) at rt for
3
h and the solvent was evaporated in vacuum. Then, the click reaction was carried out using alkyne (5 equiv) in THF (2 mL) and water (2 mL) in the
4
presence of L-sodium ascorbate (100 mol%) at rt for 20 h. (a) NaBH (4 equiv), THF (3 mL) and EtOH (7 mL), 1 h, r.t. (b) NaH (4 equiv), propargyl
bromide (5 equiv), THF (3 mL), 20 h, r.t.

10
Tetrahedron
ACCEPTED MANUSCRIPT
Table 8. Synthesis of new class of bis-1,2,3-triazole incorporated polyether macrocycles 16 and 17
.
Further, we aimed to elaborate the scope of this work by
We also explored the synthetic utility of representative 1,2,3-
triazoles and in this regard, initially we carried out the reaction of
MeI with the 1,2,3-triazole 4o in which we observed the
27
synthesizing polyethers embedded with bis-triazole moieties (8
Table 6). Towards this end, at first, we prepared the bis-
homoallylic alcohols 7a-d from the Zn-mediated allylation of the
corresponding bis-aldehydes, which were assembled from
salicyladehyde and a suitable linker (aliphatic linker or polyether
30
formation of an ionic liquid-type product 10. Presumably, in the
reaction of MeI with 4o, the product 10 formed via the loss of the
allylic moiety present in the 1,2,3-triazole derivative 4o (Scheme
2). To avoid the elimination of the allylic moiety present in the
1,2,3-triazole system, in a succeeding reaction, at first we carried
out the hydrogenation of the olefin moiety present in the 1,2,3-
triazole system 4c, which gave the 1,2,3-triazole system 11.
Then, the reaction of the 1,2,3-triazole system 11 with MeI gave
an ionic liquid-type product 12 (Scheme 2). We also carried out
the hydrogenation of a representative azide compound 2, which
gave the benzylamine substrate 13 (1,3-diphenylpropan-1-amine)
in 50% yield (Scheme 2).
27
linker or aromatic linker). Then, the bis-homoallylic alcohols
having aliphatic linker (7a), polyether linker (7b,c) and aromatic
linkers (7d) were treated with TMSN (3 equiv) in the presence
3
of Cu(OTf) (10 mol%) at rt in DCM for 3 h and after this period,
2
the solvent was evaporated and subsequently, we performed the
click reaction of the corresponding azides obtained in the
azidation step with ethyl propiolate, which gave the
corresponding compounds 8a-d with bis-triazole moieties linked
through suitable linkers in 72-87% yields, (entries 1-4, Table 6).
Similarly, the compound 8e with bis-triazole moieties linked
through suitable linkers was obtained in 68% yield from the
direct azidation of the corresponding bis-homoallylic alcohols 7a
followed by the click reaction with 3i (entries 5, Table 6).
There have been various reports on the synthesis of polyethers
27
embedded with bis-triazole moieties and 1,2,3-trizole moiety
28
incorporated macrocyclic systems. For example, recently, Beer
et al. reported the synthesis of Ferrocene-based triazole moiety

1
1
2
8e
incorporated macrocycles. Along this line an
A
d
C
in
C
co
E
n
P
tin
T
ua
E
ti
D
on MA
m
N
ole
U
cu
S
le
C
s
R
7,IP
8 and 14-17 were isolated as a mixture of
T
of our interest on the synthesis of macrocyclic polyethers/crown
diastereomers (dr = 50:50) and we could not separate the
diastereomers and characterization data given for both isomers.
29
ethers, we also intended to prepare the 1,2,3-trizole moiety
incorporated macrocyclic polyether involving the direct azidation
of alcohol as one of the steps. In this regard, the compounds 8f-h
with bis-triazole moieties linked through a polyether linker were
General procedure for the magnetic nano Fe
direct azidation of allylic/benzylic alcohol, Step ‘1’. A round-
bottom flask containing mixture of the corresponding
allylic/benzylic alcohol 1 (0.5 mmol, 1 equiv), trimethylsilyl
azide (1.25-1.5 mmol, 2.5-3 equiv) and magnetic nano Fe
(particle size < 50 nm, 15 mol% and the Fe nanoparticles can
O -catalyzed
3
4
a
treated with NaBH to afford the compounds 14a-c (Table 7).
4
Then, the compounds 14a-c were treated with propargyl bromide
in the presence of NaH to give the products 15a-c having two
terminal alkyne units. Next, the Glaser–Eglinton–Hay-type
of substrate 15a-c in the presence of
Cu(OAc) ·H O in DMSO at 110 C under an open-air atmosphere
gave a new class of polyether macrocyclic systems 16a-c (Table
) embedded with 1,2,3-triazole moieties and the 1,3-diyne unit.
Consequently, we planned to convert the 1,2-diyne unit present
in the compounds 16a-c into a thiophene ring . Accordingly,
the reaction of macrocycles 16a-c with Na S·xH O in the
O
3 4
O
4
3
be handled using a Teflon spatula) in 1,2-dichloroethane (1.5-3
mL) was stirred at 70 C for 6 h. The purification of the
corresponding azide product 2 and recovery of the catalyst
29b
o
cyclization
o
2
2
(Fe
‘2’. After the reaction time, a magnet was externally appended to
the RB flask, the magnetic Fe nanoparticles were gathered at
O nanoparticles) were performed as stated in Step ‘2’. Step
3 4
8
O
4
3
2
9b
the walls of the RB flask and the resulting clear solution of the
reaction mixture was transferred in to an another RB flask with
2
2
presence of catalytic amount of 1,10-phenanthroline and CuI in
DMF at 90 C under an open-air atmosphere gave a new class of
polyether macrocyclic system 17a-c embedded with 1,2,3-
the help of a dropper. Then, the catalyst (Fe
3 4
O nanoparticles)
o
was washed again using EtOAc (2 mL). The RB flask containing
o
Fe O4 nanoparticles was heated in an oven (at 100-110 C,
3
overnight) and the catalyst was reused in the next cycle. The
combined organic layers were evaporated under vacuum and
purified by column chromatography to give the corresponding
azide product 2.
triazole moieties and a thiophene ring (Table 8).
In summary, we have shown our investigations on the one-pot
direct azidation of allylic alcohols/ethers followed by click
reaction. Two methods were successfully developed for
synthesizing various substituted 1,2,3 triazole derivatives directly
from various allylic/benzylic alcohols without isolating the
corresponding azides. The first method (Method A) involved
magnetic nano Fe O -catalylzed direct azidation of various
General procedure (Method A) for the one-pot magnetic
nano Fe O -catalyzed direct azidation of allylic alcohols and
3
4
click reaction, Step ‘3’. The direct azidation of the
corresponding allylic/benzylic alcohol 1 (0.5 mmol, 1 equiv) was
carried out using the step ‘1’ procedure. Next, the catalyst (Fe O
3
4
3
4
nanoparticles) was removed using an external magnet and the
solvent was evaporated. Then, to the crude reaction mixture
obtained in the step ‘1’ procedure, THF (3 mL), water (3 mL),
allylic/benzylic alcohols with TMSN as the first step followed
3
by the Cu-catalyzed click reaction of the corresponding azides
with alkynes as the second step. The second method (Method B)
alkyne (1-1.2 mmol), CuSO .5H O (30 mol%) and sodium L-
involved the Cu(OTf) –catalyzed direct azidation of various
4
2
2
ascorbate (30 mol% ) were sequentially added. Then, the reaction
mixture was stirred at rt for 12 h, then, was extracted using
EtOAc and the combined organic layers were concentrated and
the resulting crude reaction mixture was purified by column
chromatography (50% EtOAc/Hexanes), to afford the
corresponding 1,2,3-triazole product 4/6 (see the corresponding
Tables/Schemes for specific entries).
allylic/benzylic alcohols and methyl ethers of allylic/benzylic
alcohols with TMSN3 as the first step followed by the click
reaction of the corresponding azides with alkynes as the second
step. In this method, Cu(OTf) served as a single catalyst for both
2
the azidation of alcohol and click reaction steps. We have also
shown the utility of this protocol by synthesizing new class of
polyethers embedded with triazole moiety and a 1,3-diyne unit.
General procedure for the copper(II) triflate-catalyzed one-
pot direct azidation of alcohol followed by click reaction
Experimental Section
(Method B): A solution of allylic alcohol 1 (0.5 mmol) and
TMSN (0.75 mmol, 1.5 equiv) and copper(II) triflate (5 mol%)
3
General. Melting points are uncorrected. FT-IR spectra of
in DCM (3 mL) was stirred at rt for 3 h under an inert
atmosphere. Then, DCM was removed under reduced pressure.
After this, to the resulting crude reaction mixture THF (2-3 mL),
water (2-3 mL), alkyne (1-1.25 mmol) and sodium L-ascorbate
1
compounds were recorded as thin films or KBr pellets. H and
1
3
C NMR spectra of compounds were recorded on 400 MHz and
00 MHz spectrometers (using TMS as an internal standard),
1
respectively. Column chromatography was carried out on silica
gel (100-200 mesh). Thin layer chromatography (TLC analysis)
was performed on silica gel plates or neutral Al O plates and
(50 mol%) were added and the reaction mixture was stirred at rt
for 20 h. Then, the reaction mixture was extracted using EtOAc
and the combined organic layers were evaporated and the
resulting reaction mixture was purified by silica gel column
chromatography to afford the triazole product 4/6 (See the
corresponding Tables/Schemes for specific entries).
General procedure for the copper(II) triflate-catalyzed one-
pot direct azidation of allylic and benzylic methyl ethers
followed by click reaction (Method B): A solution of allyl
2
3
components were visualized by observation under iodine.
Solvents were dried by following the standard drying methods.
Reactions were carried out in anhydrous solvent under a nitrogen
atmosphere wherever required. Solutions were dried using
anhydrous Na SO . Isolated yields of all the products were
2
4
reported and yields were not optimized and total yield (all the
isomers wherever applicable) is reported. Ratios of isomers were
determined from the NMR spectra of crude reaction mixtures or
after isolation. In some of the reactions, only the major product
isomer was isolated in pure form (in some cases, the product was
methyl ether 5 (0.5 mmol) and TMSN (0.75 mmol, 1.5 equiv)
3
and copper(II) triflate (5 mol%) in DCM (3 mL) was stirred at rt
for 3 h under an inert atmosphere. After this period, the solvent
was evaporated. Then, to the resulting reaction mixture THF (2
mL), water (2 mL), alkyne (1.25 mmol, 2.5 equiv) and sodium L-
ascorbate (50 mol%) were added and the reaction mixture was
stirred at rt for 20 h. Then, the reaction mixture was extracted by
using ethyl acetate (3 X 10 mL). The combined organic layers
were dried over anhydrous Na SO and the organic phase was
isolated as mixture of isomer). The particle size of Fe O4
3
nanoparticles (before and after usage in the reaction) was
2
3
31a
31b
31i
determined from HRTEM analysis. Compounds 1b-d, 1e,
31a
31c
31d,e
31f
31g
31h,i
31h
31i
31j
1
5
g, 1h,31l 1i,j,
4r, 4p, 5b,
j, 5k. Though the compounds 7, 8 and 14-17 have two
5d, 5f, 5h, 5i,
3
1k
2
4
remote stereocenters and due to the molecular symmetry, the

1
2
Tetrahedron
concentrated and the resulting crude reaction mixture was
(E)-4-Butyl-1-(1,3-diphenylallyl)-1H-1,2,3-triazole
(4f).
ACCEPTED MANUSCRIPT
purified by silica gel column chromatography (EtOAc/Hexanes)
to give the desired 1,2,3-trizole product 4/6 (see the
corresponding Tables/Schemes for specific entries).
Following the general procedure, 4f was obtained after
purification
(EtOAc:Hexanes = 50:50) as a colorless liquid (154 mg, 98%); Rf
(50% EtOAc/Hexanes) 0.42; IR (CH Cl ): νmax 2927, 1495,
1451,1215 and 747 cm ; H NMR (400 MHz, CDCl ): δ 7.43-
by
silica
gel
column
chromatography
(E)-Ethyl
1-(1,3-diphenylallyl)-1H-1,2,3-triazole-4-
2
2
-
1 1
carboxylate (4a). Following the general procedure, 4a was
3
H
obtained after purification by silica gel column chromatography
7.28 (11 H, m), 6.72 (1 H, dd, J = 16.1 Hz, J = 6.6 Hz), 6.51 (1
1 2
(
EtOAc:Hexanes = 30:70) as a brown solid (286 mg, 86%); Rf
H, d, J = 4.58 Hz), 6.48 (1 H, d, J = 2.8 Hz), 2.74 (2 H, t, J = 7.6
Hz), 1.71-1.63 (2 H, m), 1.42-1.35 (2 H, m), 0.94 (3 H, t, J = 7.3
(30% EtOAc/Hexanes) 0.42; mp 123-125 °C; IR (thin film): ν
max
-
1
1
13
2
982, 1727, 1449, 1202 and 1038 cm ; H NMR (400 MHz,
Hz) ppm; C NMR (100 MHz, CDCl ): δ 138.2, 135.6, 134.4,
3
C
CDCl ) δ 8.12 (1 H, s), 7.42-7.29 (10 H, m), 6.70 (1 H, dd, J =
129.1, 128.7, 128.6, 128.5, 127.4, 126.8, 125.9, 119.8, 66.2, 31.6,
25.5, 22.4, 13.9 ppm; HRMS (ESI): MNa , found 340.1773.
3
H
1
+
1
1
5.7 Hz, J = 6.8 Hz), 6.58 (1 H, d, J = 6.8 Hz), 6.50 (1 H, d, J =
2
5.7 Hz), 4.42 (2 H, q, J = 7.1 Hz), 1.40 (3 H, t, J = 7.1 Hz) ppm;
C H N Na requires 340.1790.
21
23
3
1
3
C NMR (100 MHz, CDCl ) δC 160.8, 140.3, 137.1, 135.3,
(E)-1-(1,3-Diphenylallyl)-4-hexyl-1H-1,2,3-triazole
Following the general procedure, 4g was obtained after
purification by silica gel column chromatography
(4g).
3
1
35.2, 129.3, 129.1, 128.8, 127.5, 126.9, 124.9, 66.7, 61.4, 14.3
+
ppm; HRMS (ESI): MNa , found 356.1385. C H N NaO
20
19
3
2
requires 356.1375.
(EtOAc:Hexanes = 30:70) as a colorless solid (293 mg, 85%); Rf
(
(
E)-(1-(1,3-Diphenylallyl)-1H-1,2,3-triazol-4-yl)methanol
4b). Following the general procedure, 4b was obtained after
(30% EtOAc/Hexanes) 0.42; mp 98-100 °C; IR (thin film) νmax
-
1 1
2928, 1495, 1454 and 1044 cm ; H NMR (400 MHz, CDCl ) δ
3
H
purification
by
silica
gel
column
chromatography
7.42-7.28 (11 H, m), 6.73 (1 H, dd, J = 16.1 Hz, J = 6.5 Hz),
1 2
(
EtOAc:Hexanes = 50:50) as a colorless liquid (238 mg, 82%); Rf
6.51-6.48 (2 H, m), 2.74 (2 H, t, J = 7.6 Hz), 1.72-1.67 (2 H, m),
13
(50% EtOAc/Hexanes) 0.42; IR (thin film) ν
3375, 2954,
1.39-1.29 (6 H, m), 0.89 (3 H, t, J = 6.1 Hz) ppm; C NMR (100
MHz, CDCl ) δ 148.6, 138.2, 135.7, 134.4, 129.1, 128.7, 128.6,
max
-
1 1
1
7
=
731, 1450, 1223 and 1091 cm ; H NMR (400 MHz, CDCl ) δ
3 H
3
C
.57 (1 H, s), 7.41-7.28 (10 H, m), 6.70 (1 H, dd, J = 15.6 Hz, J
128.5, 127.4, 126.8, 126.0, 119.9, 66.2, 31.6, 29.4, 29.0, 25.9,
1
2
13
+
7.2 Hz), 6.52-6.47 (2 H, m), 4.79 (2 H, s) , 3.36 (1 H, br. s);
C
22.6, 14.1 ppm; HRMS (ESI): MH , found 346.2294. C H N
2
3
28
3
NMR (100 MHz, CDCl ) δ 147.8, 137.7, 135.5, 134.7, 129.2,
requires 346.2283.
3
C
1
28.8, 128.7, 128.6, 127.5, 126.9, 125.5, 121.2, 66.5, 56.4;
(E)-1-(1,3-Diphenylallyl)-4-octyl-1H-1,2,3-triazole
Following the general procedure, 4h was obtained after
purification by silica gel column chromatography
(4h).
+
HRMS (ESI): MNa , found 314.1254. C H N ONa requires
18
17
3
3
14.1269.
E)-1-(1,3-Diphenylallyl)-4-phenyl-1H-1,2,3-triazole
Following the general procedure, 4c was obtained after
purification by silica gel column chromatography
EtOAc:Hexanes = 30:70) as a colorless solid (303 mg, 90%); Rf
30% EtOAc/Hexanes) 0.42; mp 178-179 °C; IR (thin film) ν
(
(4c).
(EtOAc:Hexanes = 30:70) as a colorless solid (343 mg, 92%); R
f
(30% EtOAc/Hexanes) 0.42; mp 99-101 °C; IR (thin film) ν
max
-
1 1
2926, 1495, 1454 and 967 cm ; H NMR (400 MHz, CDCl ) δ
3
H
(
(
2
7.43-7.28 (11 H, m), 6.72 (1 H, dd, J = 16.1 Hz, J = 6.6 Hz),
1 2
6.49 (2 H, dd, J = 12.0 Hz, J = 4.4 Hz), 2.73 (2 H, t, J = 7.7 Hz),
1 2
max
-
1
1
925, 1724, 1450, 1226 and 970 cm ; H NMR (400 MHz,
1.71-1.64 (2 H, m), 1.38-1.27 (10 H, m), 0.89 (3 H, t, J = 6.6 Hz)
13
CDCl ) δ 7.86 (2 H, d, J = 7.1 Hz), 7.79 (1 H, s), 7.45-7.31 (13
ppm; C NMR (100 MHz, CDCl ) δ 148.6, 138.2, 135.7, 134.4,
3 C
3
H
H, m), 6.77 (1 H, dd, J = 15.8 Hz, J = 6.7 Hz), 6.59-6.53 (2 H,
129.1, 128.7, 128.6, 128.5, 127.4, 126.8, 126.0, 119.8, 66.2, 31.9,
29.5, 29.3, 29.2, 25.8, 22.7, 14.1 ppm; HRMS (ESI): MH , found
1
2
13
+
m) ppm; C NMR (100 MHz, CDCl ) δC 147.9, 137.9, 135.6,
3
1
1
3
34.7, 130.5, 129.2, 128.8, 128.8, 128.6, 128.2, 127.5, 126.9,
25.8, 125.6, 118.9, 66.4 ppm; HRMS (ESI): MH , found
374.2591. C H N requires 374.2596.
(E)-2-((1-(1,3-Diphenylallyl)-1H-1,2,3-triazol-4-
yl)methoxy)benzaldehyde (4i). Following the general
procedure, 4i was obtained after purification by silica gel column
chromatography (EtOAc:Hexanes = 27:73) as a red colored solid
25
32
3
+
38.1642. C H N requires 338.1657.
23
20
3
(E)-(1-(1,3-Diphenylallyl)-1H-1,2,3-triazol-4-yl)methyl
acrylate (4d). Following the general procedure, 4d was obtained
after purification by silica gel column chromatography
(336 mg, 85%); R (30% EtOAc/Hexanes) 0.55; mp 111-113 °C;
f
-
1
1
(EtOAc:Hexanes = 30:70) as a colorless solid (321 mg, 93%); Rf
IR (thin film) νmax 3030, 1663, 1598, 1456 and 1236 cm ; H
NMR (400 MHz, CDCl ) δ 10.44 (1 H, s), 7.82 (1 H, d, J = 7.6
(
2
7
30% EtOAc/Hexanes) 0.42; mp 112-114 °C; IR (thin film) ν
max
3
H
-
1 1
926, 1495, 1454 and 1045 cm ; H NMR (400 MHz, CDCl ) δ
Hz), 7.75 (1 H, br. s), 7.54 (1 H, t, J = 7.4 Hz), 7.42-7.27 (10 H,
m), 7.17 (1 H, d, J = 8.5 Hz), 7.03 (1 H, t, J = 7.6 Hz), 6.74 (1 H,
dd, J = 16.1 Hz, J = 6.8 Hz), 6.51 (2 H, dd, J = 12.0 Hz, J = 4.4
3
H
.66 (1 H, s), 7.43-7.29 (10 H, m), 6.72 (1 H, dd, J = 15.6 Hz, J2
1
=
7.2 Hz), 6.54-6.42 (3 H, m), 6.15 (1 H, dd, J = 17.3 Hz, J =
1 2
13
1
2
1
2
13
1
0.4 Hz), 5.87 (1 H, d, J = 10.4 Hz), 5.33 (2 H, s) ppm; C NMR
Hz), 5.33 (2 H, s) ppm; C NMR (100 MHz, CDCl ) δ 189.7,
3 C
(
1
6
100 MHz, CDCl ) δ 166.0, 142.8, 137.7, 135.5, 134.9, 131.6,
160.5, 143.3, 137.7, 136.1, 135.4, 134.9, 129.2, 128.9, 128.8,
128.7, 128.6, 127.4, 126.9, 125.4, 125.0, 122.5, 121.3, 113.1,
3
C
29.2, 128.9, 128.7, 128.6, 128.0, 127.4, 126.9, 125.5, 123.1,
+
+
6.6, 57.8 ppm; HRMS (ESI): MH , found 346.1555. C H N O
66.7, 62.6 ppm; HRMS (ESI): MH , found 396.1702. C H N O
21
20
3
2
25 22
3
2
requires 346.1556.
requires 396.1712.
1,12-Bis(1-((E)-1,3-diphenylallyl)-1H-1,2,3-triazol-4-yl)-
(E)-Dimethyl
1-(1,3-diphenylallyl)-1H-1,2,3-triazole-4,5-
dicarboxylate (4e). Following the general procedure, 4e was
obtained after purification by silica gel column chromatography
2,5,8,11-tetraoxadodecane (4j). Following the general
procedure, 4j was obtained after purification by silica gel column
chromatography (EtOAc:Hexanes = 30:70) as colorless liquid
(EtOAc:Hexanes = 30:70) as yellow liquid (324 mg, 86%); Rf
(
1
7
30% EtOAc/Hexanes) 0.42; IR (thin film) ν 2950, 1735,
(522 mg, 75%); R (30% EtOAc/Hexanes) 0.42; IR (thin film)
max
f
-
1
1
-1
1
485, 1210 and 1020 cm ; H NMR (400 MHz, CDCl ) δ 7.45-
νmax 2869, 1495, 1450 and 1097 cm ; H NMR (400 MHz,
CDCl ) δ 7.60 (2 H, s), 7.41-7.28 (20 H, m), 6.71 (2 H, dd, J =
3
H
.28 (10 H, m), 6.96 (1 H, dd, J = 15.7 Hz, J = 8.0 Hz), 6.81 (1
1
2
3
H
1
H, d, J = 8.0 Hz), 6.64 (1 H, d, J = 15.7 Hz), 3.97 (3 H, s), 3.85
15.6 Hz, J = 7.2 Hz), 6.52-6.47 (4 H, m), 4.69 (4 H, s), 3.70-3.62
2
13
13
(
3 H, s) ppm; C NMR (100 MHz, CDCl ) δC 160.6, 159.3,
(8 H, m), 3.60 (4 H, s) ppm; C NMR (100 MHz, CDCl ) δC
3
3
1
1
39.8, 137.3, 135.5, 135.1, 130.2, 129.0, 128.8, 128.7, 128.6,
27.4, 127.0, 125.1, 67.1, 53.4, 52.7 ppm; HRMS (ESI): MNa ,
145.2, 137.9, 135.5, 134.7, 129.1, 128.8, 128.7, 128.5, 127.5,
126.8, 125.7, 121.9, 70.5, 70.5, 69.8, 66.4, 64.8 ppm; HRMS
+
+
found 400.1285. C H N NaO requires 400.1273.
(ESI): MH , found 697.3505. C H N O requires 697.3502.
21
19
3
4
42 45
6
4

1
3
+
(
E)-1-(1,3-Bis(4-chlorophenyl)allyl)-4-phenyl
A
-1
C
H-
C
1,2
E
,3
P
-
TED MA
M
NU
H
, f
S
ou
C
nd
R
3
I
52.1807. C24H N requires 352.1814. Isolated
P
T
22 3
triazole (4k). Following the general procedure, 4k was obtained
after purification by silica gel column chromatography
as a mixture of regioisomers and NMR values given for both
isomers.
(
EtOAc:Hexanes = 50:50) as a colorless solid (151 mg, 75%); Rf
(E)-Ethyl
1-(1-(4-nitrophenyl)-3-phenylallyl)-1H-1,2,3-
o
(30% EtOAc/Hexanes) 0.52; mp: 88-90 C; IR (CH Cl ) ν
triazole-4-carboxylate (4oA). Following the general procedure,
4oA was obtained after purification by silica gel column
chromatography (EtOAc:Hexanes = 30:70) as light yellow colour
2
2
max
-
1
1
2
928, 1595, 1491, 1407 and 764 cm ; H NMR (400 MHz,
CDCl ) δ 7.85 (2 H, dd, J = 7.1 Hz, J = 1.4 Hz), 7.79 (1 H, s),
3
H
1
2
7
6
1
1
.45-7.25 (11 H, m), 6.71 (1 H, dd, J = 15.8 Hz, J = 6.8 Hz),
liquid (128 mg, 68%); R (30% EtOAc/Hexanes) 0.42; IR (thin
1
2
f
13
-1
1
.50-6.45 (2 H, m) ppm; C NMR (100 MHz, CDCl ) δ 148.0,
film) νmax 2979, 1731, 1519, 1344 and 733 cm ; H NMR (400
MHz, CDCl ) δ 8.28-8.19 (2 H, m), 8.06 (1 H, s), 7.57-7.28 (7
3
C
36.2, 134.9, 134.4, 133.8, 133.8, 130.3, 129.4, 129.0, 128.9,
3
H
28.8, 128.4, 128.1 125.8, 125.7, 118.9, 65.7 ppm; HRMS (ESI):
H, m), 6.92 (1 H, dd, J = 15.9 Hz, J = 6.5 Hz), 6.66-6.48 (2 H,
1 2
13
+
MNa , found 428.0672. C H Cl N Na requires 428.0697.
m), 4.43 (2 H, q, J = 7.1 Hz), 1.40 (3 H, t, J = 7.1 Hz) ppm;
C
23
17
2
3
(E)-Ethyl 1-(1,3-bis(4-chlorophenyl)allyl)-1H-1,2,3-triazole-4-
NMR (100 MHz, CDCl ) δ 160.7, 147.6, 141.6, 140.4, 137.1,
3
C
carboxylate (4l). Following the general procedure, 4l was
obtained after purification by silica gel column chromatography
136.1, 132.5, 129.8, 129.6, 129.6, 129.3, 128.9, 128.2, 127.7,
127.7, 127.5, 127.0, 127.0, 126.9, 124.4, 124.1, 123.0, 66.5, 66.0,
61.6, 61.5, 14.3 ppm; HRMS (ESI): MNa , found 401.1239.
+
(EtOAc:Hexanes = 50:50) as a colorless liquid (120 mg, 60%); Rf
(
1
30% EtOAc/Hexanes) 0.48; IR (CH Cl ) ν 2983, 1731, 1594,
C H N NaO requires 401.1226. Isolated as a mixture of
2
2
max
20 18
4
4
-
1 1
492, 1093 and 737 cm ; H NMR (400 MHz, CDCl ) δ 8.10
regioisomers and NMR values given for both isomers.
Ethyl 1-cinnamyl-1H-1,2,3-triazole-4-carboxylate
Following the general procedure, 4p was obtained after
purification by silica gel column chromatography
3
H
(1 H, s), 7.39 (2 H, d, J = 8.5 Hz), 7.32 (4 H, s), 7.23 (2 H, d, J =
(4p).
8
=
=
.4 Hz), 6.65 (1 H, dd, J = 15.8 Hz, J = 6.5 Hz), 6.54 (1 H, d, J
1 2
6.9 Hz), 6.46 (1 H, dd, J = 15.8 Hz, J = 1.1 Hz), 4.42 (2H, q, J
1
2
13
7.1 Hz), 1.40 (3 H, t, J = 7.1 Hz) ppm; C NMR (100 MHz,
(EtOAc:Hexanes = 50:50) as a colorless solid (89 mg, 70%); R
f
o
CDCl ) δ 160.6, 140.4, 135.4, 135.3, 134.7, 134.4, 133.5, 129.6,
1
(30% EtOAc/Hexanes) 0.42; mp: 87-89 C; IR (CH Cl ) ν
3
C
2
2
max
-
1
1
29.0, 128.8, 128.1, 126.8, 125.0, 66.0, 61.5, 14.3 ppm; HRMS
3139, 2983, 1731, 1450 and 759 cm ; H NMR (400 MHz,
+
(ESI): MNa , found 424.0578. C H Cl N NaO requires
CDCl ) δ 8.16 (1 H, s), 7.39-7.28 (5 H, m), 6.69 (1 H, d, J =
20
17
2
3
2
3
H
4
24.0596.
15.8 Hz), 6.36-6.29 (1 H, m), 5.18 (2 H, d, J = 6.7 Hz), 4.39 (2
13
(E)-Dimethyl
1-(1,3-bis(4-chlorophenyl)allyl)-1H-1,2,3-
H, q, J = 7.1 Hz), 1.38 (3 H, t, J = 7.1 Hz) ppm; C NMR (100
MHz, CDCl ) δ 160.7, 140.7, 136.2, 135.2, 128.8, 127.3, 126.8,
triazole-4,5-dicarboxylate (4m). Following the general
procedure, 4m was obtained after purification by silica gel
column chromatography (EtOAc:Hexanes = 30:70) as a yellow
3
C
+
120.9, 61.3, 52.6, 14.3 ppm; HRMS (ESI): MNa , found
280.1059. C H N NaO requires 280.1062.
14
15
3
2
liquid (232 mg, 52%); R (30% EtOAc/Hexanes) 0.42; IR (thin
(E)-Ethyl
1-(4-phenylbut-3-en-2-yl)-1H-1,2,3-triazole-4-
f
-
1
1
film): νmax 2954, 1732, 1491, 1224 and 1092 cm ; H NMR (400
MHz, CDCl ) δ 7.37-7.26 (8 H, m), 6.88 (1 H, dd, J = 15.6 Hz,
carboxylate (4q). Following the general procedure, 4q was
obtained after purification by silica gel column chromatography
3
H
1
J = 7.7 Hz), 6.80 (1 H, d, J = 7.8 Hz), 6.56 (1 H, d, J = 15.6 Hz),
(EtOAc:Hexanes = 50:50) as a colorless solid (102 mg, 76%); R
2
f
13
o
3
1
1
.98 (3 H, s), 3.90 (3 H, s) ppm; C NMR (100 MHz, CDCl ) δ
60.5, 159.2, 140.1, 135.6, 135.0, 134.5, 134.1, 133.8, 129.6,
(30% EtOAc/Hexanes) 0.50; mp: 77-79 C; IR (CH Cl ) ν
2984, 1738, 1494, 1376 and 754 cm ; H NMR (400 MHz,
3
C
2
2
max
-
1
1
29.3, 129.0, 128.9, 128.2, 125.4, 66.1, 53.5, 52.8 ppm; HRMS
CDCl ) δ 8.16 (1 H, s), 7.37-7.24 (5 H, m), 6.59 (1 H, d, J =
3
H
+
(
ESI): MNa , found 468.0487. C H Cl N NaO requires
15.9 Hz), 6.35 (1 H, dd, J = 15.9 Hz, J = 6.9 Hz), 5.49-5.44 (1
21
17
2
3
4
1 2
4
68.0494.
H, m), 4.39 (2 H, q, J = 7.1 Hz), 1.80 (3 H, d, J = 6.9 Hz), 1.37 (3
13
(E)-1-(3-(4-Bromophenyl)-1-phenylallyl)-4-hexyl-1H-1,2,3-
H, t, J = 7.1 Hz) ppm; C NMR (100 MHz, CDCl ) δ 160.8,
3 C
triazole (4n). Following the general procedure, 4n was obtained
after purification by silica gel column chromatography
140.1, 135.3, 133.5, 128.7, 128.6, 126.8, 126.7, 125.9, 61.2, 59.0,
20.9, 14.3 ppm; HRMS (ESI): MNa , found 294.1208.
+
(EtOAc:Hexanes = 30:70) as colorless liquid (346 mg, 82%); Rf
C H N NaO requires 294.1218.
15
17
3
2
(
1
7
30% EtOAc/Hexanes) 0.42; IR (thin film) ν 2927, 2857,
588, 1488 and 1071 cm ; H NMR (400 MHz, CDCl ) δ 7.53-
3 H
.13 (10 H, m), 6.75-6.64 (1 H, m), 6.51-6.38 (2 H, m), 2.75-2.70
(E)-4-Hexyl-1-(4-phenylbut-3-en-2-yl)-1H-1,2,3-triazole (4r).
Following the general procedure, 4r was obtained after
max
-
1
1
purification
by
silica
gel
column
chromatography
(
2 H, m), 1.69-1.65 (2 H, m), 1.38-1.28 (6 H, m), 0.88 (3 H, t, J =
(EtOAc:Hexanes = 50:50) as a colorless liquid (120 mg, 85%); Rf
13
6
1
1
1
.8 Hz) ppm; C NMR (100 MHz, CDCl ) δC 148.8, 148.7,
(30% EtOAc/Hexanes) 0.45; IR (CH Cl ) ν 3028, 1482, 1448,
3
2
2
max
-
1 1
37.9, 137.3, 135.4, 134.9, 134.6, 133.1, 132.2, 131.8, 129.1,
29.1, 128.8, 128.7, 128.3, 127.4, 126.9, 126.9, 125.3, 122.7,
1178 and 764 cm ; H NMR (400 MHz, CDCl ) δ 7.36-7.20 (6
3 H
H, m), 6.52 (1 H, d, J = 16.0 Hz), 6.35 (1 H, dd, J = 15.9 Hz, J =
1
2
22.3, 119.9, 119.8, 66.1, 65.6, 31.5, 29.4, 29.0, 25.8, 22.6, 14.1
6.6 Hz), 5.38-5.31 (1 H, m), 2.70 (2 H, t, J = 7.9 Hz), 1.75 (3 H,
d, J = 6.9 Hz), 1.69-1.62 (2 H, m), 1.36-1.22 (6 H, m), 0.86 (3 H,
+
ppm; HRMS (ESI): MH , found 424.1386. C H BrN requires
4
23
27
3
13
24.1388. Isolated as a mixture of regioisomers and NMR values
t, J = 7.0 Hz) ppm; C NMR (100 MHz, CDCl ) δ 148.4, 135.7,
3 C
given for both isomers.
132.4, 128.7, 128.3, 128.1, 126.6, 118.9, 58.2, 31.6, 29.5, 29.0,
25.8, 22.6, 20.8, 14.1 ppm; HRMS (ESI): MH , found 284.2115.
+
(E)-4-Phenyl-1-(3-phenyl-1-(p-tolyl)allyl)-1H-1,2,3-triazole
4o). Following the general procedure, 4o was obtained after
(
C H N requires 284.2127.
18
26
3
purification
(
(
by
EtOAc:Hexanes = 30:70) as colorless solid (253 mg, 72%); Rf
30% EtOAc/Hexanes) 0.42; mp 134-136 °C; IR (thin film) ν
silica
gel
column
chromatography
1-((2E,4E)-1,5-Diphenylpenta-2,4-dien-1-yl)-4-phenyl-1H-
1,2,3-triazole (4s). Following the general procedure, 4s was
obtained after purification by silica gel column chromatography
(EtOAc:Hexanes = 30:70) as a colorless solid (225 mg, 62%); Rf
max
-
1
1
2
930, 1482, 1456, 1224 and 970 cm ; H NMR (400 MHz,
CDCl ) δ 7.87 (2 H, d, J = 7.5 Hz), 7.82 (1 H, s), 7.55-7.19 (12
H, m), 6.85-6.33 (3 H, m), 2.32 (3 H, s) ppm; C NMR (100
(30% EtOAc/Hexanes) 0.42; mp 131-133 °C; IR (thin film) ν
3
H
max
13
-1 1
3028, 1494, 1449 and 990 cm ; H NMR (400 MHz, CDCl ) δ
3 H
MHz, CDCl ) δ 147.9, 147.6, 138.1, 136.7, 136.0, 135.7, 135.6,
7.87 (2 H, d, J = 8.4 Hz), 7.77 (1 H, s), 7.47-7.26 (13 H, m), 6.88
(1 H, dd, J = 15.6 Hz, J = 8.4 Hz), 6.60 (1 H, d, J = 15.6 Hz),
3
C
1
1
1
34.8, 133.8, 132.8, 131.3, 130.6, 130.5, 129.2, 128.9, 128.5,
28.2, 127.4, 127.3, 127.0, 126.8, 126.8, 126.3, 126.0, 125.8,
25.7, 119.2, 118.8, 66.6, 63.0, 19.8, 19.2 ppm; HRMS (ESI):
1
2
13
6.52 (1 H, d, J = 5.6 Hz), 6.40-6.28 (2 H, m) ppm; C NMR (100
MHz, CDCl ) δ 147.8, 137.8, 136.6, 135.1, 134.9, 130.6, 129.2,
3
C

1
4
Tetrahedron
ACCEPTED MANUSCRIPT
+
1
29.1, 128.9, 128.8, 128.8, 128.7, 128.2, 128.1, 127.5, 127.0,
61.4, 34.0, 31.9, 31.5, 29.5, 14.4 ppm; HRMS (ESI): MNa ,
found 408.1696. C H N NaO requires 408.1688. Isolated as a
+
1
3
26.6, 125.8, 118.9, 66.2 ppm; HRMS (ESI): MNa , found
86.1622. C H N Na requires 386.1633.
24
23
3
2
mixture of regioisomers and the characterization data given
correspond to both isomers and *corresponds to the minor isomer
in the H NMR.
25
21
3
Ethyl 1-((2E,4E)-1,5-diphenylpenta-2,4-dien-1-yl)-1H-1,2,3-
triazole-4-carboxylate (4t). Following the general procedure, 4t
was obtained after purification by silica gel column
chromatography (EtOAc:Hexanes = 50:50) as a colorless liquid
1
Ethyl 1-(2-methyl-5-(prop-1-en-2-yl)cyclohex-2-en-1-yl)-1H-
1,2,3-triazole-4-carboxylate (4x). Following the general
procedure, 4x was obtained after purification by silica gel column
chromatography (EtOAc:Hexanes = 50:50) as a colorless liquid
(110 mg, 80%); R (50% EtOAc/Hexanes) 0.42; IR (CH Cl ) ν
(131 mg, 73%); R (30% EtOAc/Hexanes) 0.32; IR (CH Cl ) ν
f
2
2
max
-
1
1
2
983, 1731, 1449, 1377 and 736 cm ; H NMR (400 MHz,
CDCl ) δ 8.10 (1 H, s), 7.41-7.38 (5 H, m), 7.33 (2 H, t, J = 7.5
3
H
f
2
2
max
-
1
1
Hz), 7.29-7.26 (3 H, m), 6.87-6.81 (1 H, m), 6.59 (1 H, d, J =
5.7 Hz), 6.51 (1 H, d, J = 5.3 Hz), 6.29-6.26 (2 H, m), 4.42 (2
3132, 2977, 1731, 1645, 1538 and 735 cm ; H NMR (400
MHz, CDCl ) δ 8.02*/8.01 (1 H, s), 5.92 (1 H, br. s), 5.12 (1 H,
br. s), 4.64 (1 H, s), 4.57 (1 H, s), 4.34 (2 H, q, J = 7.0 Hz), 2.29-
1.89 (5 H, m), 1.58 (6 H, s), 1.32 (3 H, t, J = 7.1 Hz) ppm;
1
3
H
13
H, q, J = 7.2 Hz), 1.40 (3 H, t, J = 7.0 Hz) ppm; C NMR (100
MHz, CDCl ) δ 160.8, 140.2, 137.1, 136.5, 135.5, 135.4, 129.3,
13
C
3
C
1
1
29.1, 128.7, 128.2, 128.2, 127.5, 126.9, 126.7, 126.6, 66.5, 61.4,
NMR (100 MHz, CDCl ) δ 160.9, 160.8, 147.2, 147.0, 140.2,
3
C
+
4.4 ppm; HRMS (ESI): MNa , found 382.1522. C H N NaO
139.6, 130.4, 130.0, 128.2, 127.7, 126.7, 126.0, 109.9, 109.9,
62.5, 61.2, 61.2, 60.0, 40.4, 36.5, 34.8, 34.6, 30.5, 30.3, 20.8,
22
21
3
2
requires 382.1531.
2
+
-((1-((2E,4E)-1,5-Diphenylpenta-2,4-dien-1-yl)-1H-1,2,3-
20.7, 20.6, 20.5, 18.8, 14.3 ppm; HRMS (ESI): MNa , found
triazol-4-yl)methoxy)benzaldehyde (4u). Following the general
procedure, 4u was obtained after purification by silica gel
column chromatography (EtOAc:Hexanes = 30:70) as yellow
298.1519. C H N NaO requires 298.1531. Isolated as a mixture
15
21
3
2
of diastereomers and the characterization data given correspond
1
to both isomers and *corresponds to the minor isomer in the H
liquid (240 mg, 57%); R (30% EtOAc/Hexanes) 0.42; IR (thin
NMR.
f
-
1 1
film) νmax 3030, 1663, 1598, 1456 and 1236 cm ; H NMR (400
MHz, CDCl ) δ 10.46 (1 H, s), 7.85 (1 H, d, J = 7.5 Hz), 7.67 (1
4-Hexyl-1-(2-methyl-5-(prop-1-en-2-yl)cyclohex-2-en-1-yl)-
1H-1,2,3-triazole (4y). Following the general procedure, 4y was
obtained after purification by silica gel column chromatography
(EtOAc:Hexanes = 50:50) as a colorless liquid (124 mg, 87%); Rf
(50% EtOAc/Hexanes) 0.42; IR (CH Cl ): ν 3131, 2926, 2857,
3
H
H, s), 7.57 (1 H, t, J = 8.5 Hz), 7.42-7.26 (10 H, m), 7.19 (1 H, d,
J = 8.4 Hz), 7.08 (1 H, t, J = 7.5 Hz), 6.86 (1 H, dd, J = 15.6 Hz,
1
J = 9.4 Hz), 6.57 (1 H, d, J = 15.6 Hz), 6.46 (1 H, d, J = 5.7 Hz),
2
2
2
max
13
-1 1
6
.36-6.24 (2 H, m), 5.36 (2 H, s) ppm; C NMR (100 MHz,
1548, 1377 and 809 cm ; H NMR (400 MHz, CDCl ): δ 7.25
3 H
CDCl ) δ 189.7, 160.5, 143.4, 137.6, 136.5, 136.1, 135.2, 135.2,
(1 H, s), 5.90 (1 H, br. s), 5.08 (1 H, br. s), 4.72 (1 H, s), 4.65 (1
3
C
1
1
29.2, 128.9, 128.7, 128.7, 128.6, 128.2, 127.4, 126.9, 126.6,
25.1, 122.2, 121.4, 113.1, 66.5, 62.7 ppm; HRMS (ESI): MH ,
H, s), 2.70 (2 H, t, J = 7.8 Hz), 2.34-1.90 (5 H, m), 1.66-1.62 (8
+
13
H, m), 1.35-1.25 (6 H, m), 0.86 (3 H, t, J = 6.8 Hz) ppm;
C
found 422.1858. C H N O requires 422.1869.
NMR (100 MHz, CDCl ): δ 148.6, 147.8, 147.7, 147.5, 131.2,
27
24
3
2
3 C
(
E)-Ethyl
yl)(phenyl)methyl)-1H-1,2,3-triazole-4-carboxylate
Following the general procedure, 4v was obtained after
purification by silica gel column chromatography
EtOAc:Hexanes = 30:70) as a colorless solid (247 mg, 62%); Rf
30% EtOAc/Hexanes) 0.42; mp 135-137 °C; IR (thin film) ν
1-((3-benzylidenecyclohex-1-en-1-
129.1, 128.9, 127.1, 119.7, 118.8, 109.7, 61.8, 59.2, 40.7, 36.5,
35.3, 34.9, 31.5, 30.6, 30.4, 29.4, 28.9, 25.8, 25.7, 22.5, 20.8,
20.7, 20.5, 18.9, 14.0 ppm; HRMS (ESI): MH , found 288.2436.
(4v).
+
C H N requires 288.2440. Isolated as
a
mixture of
18
30
3
(
(
2
diastereomers and the characterization data given correspond to
both isomers.
Ethyl 1-benzhydryl-1H-1,2,3-triazole-4-carboxylate (6a).
Following the general procedure, 6a was obtained after
max
-
1
1
936, 1722, 1447, 1224 and 1038 cm ; H NMR (400 MHz,
CDCl ) δ 8.01/7.90* (1 H, s), 7.44-7.20 (9 H, m), 7.04 (1 H, d,
3
H
J = 7.2 Hz), 6.48/6.35* (1 H, s), 6.25/6.17* (1 H, s), 5.74 (1 H,
s), 4.44 (2 H, q, J = 7.2 Hz), 2.68-2.65/2.48-2.45* (2 H, m), 2.12
purification
by
silica
gel
column
chromatography
(EtOAc:Hexanes = 30:70) as a colorless solid (218 mg, 71%); Rf
(
=
2 H, t, J = 5.8 Hz), 1.88-1.85*/1.80-1.73 (2 H, m), 1.42 (3 H, t, J
(30% EtOAc/Hexanes) 0.42; mp 146-148 °C; IR (thin film) ν
2983, 1722, 1453, 1207 and 1041 cm ; H NMR (400 MHz,
max
13
-1
1
7.2 Hz) ppm; C NMR (100 MHz, CDCl ) δ 160.9, 139.9,
3
C
1
1
1
2
4
38.5, 137.2, 136.6, 135.7, 135.6, 134.3, 131.4, 129.4, 129.3,
29.3, 129.2, 129.1, 128.9, 128.3, 128.2, 128.2, 128.1, 127.5,
27.1, 126.7, 126.6, 125.3, 70.1, 70.0, 61.4, 61.3, 31.9, 28.0,
CDCl ) δ 7.94 (1 H, s), 7.39-7.37 (6 H, m), 7.18 (1 H, s), 7.12-
3
H
7.10 (4 H, m), 4.40 (2 H, q, J = 7.1 Hz), 1.39 (3 H, t, J = 7.1 Hz)
1
3
ppm; C NMR (100 MHz, CDCl ) δ 160.8, 140.0, 137.4, 129.1,
3
C
+
+
7.6, 26.4, 22.9, 22.5, 14.4 ppm; HRMS (ESI): MNa , found
128.9, 128.0, 127.7, 68.4, 61.4, 14.3 ppm; HRMS (ESI): MH ,
found 308.1398. C H N O requires 308.1399.
22.1844. C H N NaO requires 422.1844. Isolated as a
25
25
3
2
18 18
3
2
mixture of regioisomers and the characterization data given
correspond to both isomers and *corresponds to the minor isomer
in the H NMR.
Ethyl 1-(1-phenylethyl)-1H-1,2,3-triazole-4-carboxylate (6b).
Following the general procedure, 6b was obtained after
1
purification
(EtOAc:Hexanes = 30:70) as yellow liquid (87 mg, 35%); R
(30% EtOAc/Hexanes) 0.42; IR (thin film) νmax 2926, 1731,
by
silica
gel
column
chromatography
(
E)-Ethyl
yl)(phenyl)methyl)-1H-1,2,3-triazole-4-carboxylate
Following the general procedure, 4w was obtained after
purification by silica gel column chromatography
EtOAc:Hexanes = 30:70) as a colorless solid (173 mg, 45%); Rf
30% EtOAc/Hexanes) 0.42; mp 153-155 °C; IR (thin film) ν
1-((3-benzylidenecyclopent-1-en-1-
f
(4w).
-
1 1
1375, 1220 and 1095 cm ; H NMR (400 MHz, CDCl ) δ 7.97
3
H
(1 H, s), 7.43-7.37 (3 H, m), 7.31-7.29 (2 H, m), 5.90 (1 H, q, J =
7.1 Hz), 4.41 (2 H, q, J = 7.1 Hz), 2.02 (3 H, d, J = 7.1 Hz), 1.40
(
(
2
13
(3 H, t, J = 7.1 Hz) ppm; C NMR (100 MHz, CDCl ) δ 160.9,
max
3 C
-
1
1
926, 1724, 1448, 1202 and 1039 cm ; H NMR (400 MHz,
140.2, 138.9, 129.2, 129.0, 126.6, 126.2, 61.3, 60.7, 21.2, 14.3
+
CDCl ) δ 8.05/8.00* (1 H, s), 7.45-7.43 (3 H, m), 7.34 (5 H, d, J
ppm; HRMS (ESI): MH , found 246.1252. C H N O requires
3
H
13 16
3
2
=
4.4 Hz), 7.22-7.17 (1 H, m), 6.61 (1 H, s), 6.35 (1 H, s), 5.90 (1
246.1243.
H, s), 4.44 (2 H, q, J = 7.1 Hz), 3.02-2.99 (2 H, m), 2.63-2.60 (2
Ethyl
1-(1,2,3,4-tetrahydronaphthalen-1-yl)-1H-1,2,3-
13
H, m), 1.42 (3 H, t, J = 7.1 Hz) ppm; C NMR (100 MHz,
CDCl ) δ 160.8, 160.8, 150.7, 147.0, 145.8, 146.4, 140.1, 140.0,
triazole-4-carboxylate (6c). Following the general procedure, 6c
was obtained after purification by silica gel column
chromatography (EtOAc:Hexanes = 30:70) as a colorless solid
3
C
1
1
38.1, 137.9, 136.7, 135.6, 135.4, 130.6, 129.4, 128.5, 128.1,
28.0, 128.0, 127.8, 127.0, 126.3, 126.3, 122.3, 120.7, 66.4, 66.2,
(190 mg, 70%); R (30% EtOAc/Hexanes) 0.42; mp 86-88 °C; IR
f

1
5
-
1 1
(
(
thin film) νmax 2939, 1721, 1452, 1198 and 1038 cm ; H NMR
400 MHz, CDCl ) δ 7.69 (1 H, s), 7.26-7.10 (3 H, m), 6.89 (1
H, m), 2.86 (2 H, s), 2.57-2.42 (4 H, m), 1.83-1.81 (4 H, m),
13
ACCEPTED MANUSCRIPT
1.56-1.54 (4 H, m) ppm; C NMR (100 MHz, CDCl ) δ 155.7,
3
H
3
C
H, d, J = 7.6 Hz), 5.95 (1 H, t, J = 5.1 Hz), 4.31 (2 H, q, J = 7.1
135.4, 132.1, 128.2, 126.8, 120.6, 117.4, 111.2, 69.6, 67.6, 42.1,
29.3, 26.0 ppm; HRMS (ESI): MNa , found 433.2357.
C H NaO requires 433.2355. Isolated as a mixture of
26 34 4
+
Hz), 2.93-2.78 (2 H, m), 2.31-2.26 (2 H, m), 1.89-1.81 (1 H, m),
13
1
.74-1.68 (1 H, m), 1.32 (3 H, t, J = 7.1 Hz) ppm; C NMR (100
MHz, CDCl ) δ 160.8, 139.7, 137.9, 131.6, 129.8, 129.1,128.9,
diastereomers (dr = 50:50) and NMR values given for both
isomers.
General procedure for the one-pot synthesis of 1,2,3-triazoles
8a-h directly from bis-homoallylic alcohols 7a-d. A solution of
the corresponding bis-homoallylic alcohol 7 (0.5 mmol) and
3
C
1
27.1, 126.8, 61.2, 59.4, 30.9, 28.6, 18.9, 14.3 ppm; HRMS
+
(ESI): MH , found 272.1390. C H N O requires 272.1399.
15
18
3
2
Ethyl 1-(1-allyl-1,2,3,4-tetrahydronaphthalen-1-yl)-1H-1,2,3-
triazole-4-carboxylate (6d). Following the general procedure,
6
d was obtained after purification by silica gel column
chromatography (EtOAc:Hexanes = 30:70) as a colorless liquid
162 mg, 52%); R (30% EtOAc/Hexanes) 0.42; IR (thin film)
TMSN (1.5 mmol, 3 equiv) and copper(II) triflate (10 mol%) in
3
DCM (5.0 mL) was stirred at rt for 3 h under an inert
atmosphere. After this period, the solvent was evaporated. Then,
to the resulting reaction mixture THF (2-3 mL), water (2-3 mL),
alkyne (2.5 mmol, 5 equiv) and sodium L-ascorbate (100 mol%)
were added and stirred at rt for 20 h. Then, the reaction mixture
was extracted by using ethyl acetate (3 X 10 mL). The combined
(
f
-
1 1
νmax 2939, 1739, 1319, 1221 and 773 cm ; H NMR (400 MHz,
CDCl ) δ 7.52 (1 H, s), 7.34-7.21 (4 H, m), 5.59-5.48 (1 H, m),
5
1
2
3
H
.24-5.07 (2 H, m), 4.36 (2 H, q, J = 7.1 Hz), 3.52 (1 H, dd, J =
1
4.4 Hz, J = 8.4 Hz), 3.24-3.19 (1 H, m), 2.84-2.80 (2 H, m),
2
.56-2.51 (1 H, m), 2.32-2.24 (1 H, m), 1.85-1.78 (1 H, m), 1.35
organic layers were dried over anhydrous Na SO and the organic
2 4
13
(3 H, t, J = 7.1 Hz), 1.38-1.34 (1 H, m) ppm; C NMR (100
phase was concentrated, and the resulting crude reaction mixture
was purified by silica gel column chromatography
(EtOAc/Hexanes) to give the desired 1,2,3-bis-triazole product 8
(see the corresponding Tables/Schemes for specific entries).
MHz, CDCl ) δ 161.1, 138.7, 138.6, 134.0, 132.5, 130.2, 129.0,
1
ppm; HRMS (ESI): MH , found 312.1704. C H N O requires
3
C
28.3, 127.8, 127.0, 120.0, 66.1, 61.2, 45.0, 35.1, 29.5, 18.2, 14.3
+
18
22
3
2
3
4
12.1712.
-Hexyl-1-(1,2,3,4-tetrahydronaphthalen-1-yl)-1H-1,2,3-
Diethyl
1,1'-(((hexane-1,6-diylbis(oxy))bis(2,1-
phenylene))bis(but-3-ene-1,1-diyl))bis(1H-1,2,3-triazole-4-
carboxylate) (8a). Following the general procedure, 8a was
obtained after purification by silica gel column chromatography
(EtOAc:Hexanes = 50:50) as a red color liquid (117 mg, 72%);
R (50% EtOAc/Hexanes) 0.45; IR (CH Cl ) ν 2939, 1738,
triazole (6e). Following the general procedure, 6e was obtained
after purification by silica gel column chromatography
(EtOAc:Hexanes = 30:70) as yellow liquid (198 mg, 70%); Rf
(30% EtOAc/Hexanes) 0.42; IR (thin film) ν 2928, 1454, 1219
max
f
2
2
max
-
1
1
-1 1
and 1042 cm ; H NMR (400 MHz, CDCl ) δ 7.28 (1 H, t, J =
1602, 1542, 1494 and 754 cm ; H NMR (400 MHz, CDCl ) δ
3
H
3 H
7
.7 Hz), 7.21 (1 H, d, J = 6.1 Hz), 7.15 (1 H, t, J = 7.7 Hz), 6.95
8.04 (2 H, s), 7.34-7.28 (4 H, m), 6.97 (2 H, t, J = 7.5 Hz), 6.91
(2 H, d, J = 8.6 Hz), 6.14 (2 H, t, J = 7.1 Hz), 5.74-5.70 (2 H, m),
5.14-5.02 (4 H, m), 4.38 (4 H, q, J = 7.2 Hz), 4.02-3.93 (4 H, m),
3.24-3.18 (2 H, m), 3.06-3.02 (2 H, m), 1.82-1.79 (4 H, m), 1.47-
(1 H, s), 6.91 (1 H, d, J = 7.7 Hz), 5.93 (1 H, t, J = 6.1 Hz), 3.00-
2
1
.83 (2 H, m), 2.67 (2 H, t, J = 7.5 Hz), 2.35-2.24 (2 H, m), 1.92-
.84 (2 H, m), 1.66-1.59 (2 H, m), 1.35-1.27 (6 H, m), 0.87 (3 H,
13
13
t, J = 6.8 Hz) ppm; C NMR (100 MHz, CDCl ) δ 148.2, 137.7,
1.44 (4 H, m), 1.37 (6 H, t, J = 7.1 Hz) ppm; C NMR (100
3
C
1
2
2
33.1, 129.5, 128.9, 128.3, 126.6, 119.8, 58.9, 31.5, 31.3, 29.4,
8.9, 25.8, 22.5, 19.7, 14.0 ppm; HRMS (ESI): MH , found
MHz, CDCl ) δ 161.0, 156.1, 139.5, 132.9, 130.2, 127.5, 127.2,
3
C
+
127.2, 125.4, 120.7, 118.9, 111.7, 67.9, 61.2, 59.2, 59.2, 38.1,
+
84.2118. C H N requires 284.2127.
29.0, 25.8, 14.3 ppm; HRMS (ESI): MNa , found 679.3224.
18
26
3
Ethyl
1-(phenyl(o-tolyl)methyl)-1H-1,2,3-triazole-4-
C H N NaO requires 679.3220. Isolated as a mixture of
36 44 6 6
carboxylate (6f). Following the general procedure, 6f was
diastereomers (dr = 50:50) and NMR values given for both
obtained after purification by silica gel column chromatography
isomers.
(EtOAc:Hexanes = 50:50) as a colorless liquid (139 mg, 87%); Rf
Diethyl
1,1'-((((oxybis(ethane-2,1-diyl))bis(oxy))bis(2,1-
(
1
7
50% EtOAc/Hexanes) 0.42; IR (CH Cl ) ν 2985, 1738, 1491,
phenylene))bis(but-3-ene-1,1-diyl))bis(1H-1,2,3-triazole-4-
carboxylate) (8b). Following the general procedure, 8b was
obtained after purification by silica gel column chromatography
(EtOAc:Hexanes = 50:50) as a colorless liquid (135 mg, 84%); Rf
2
2
max
-
1 1
375 and 754 cm ; H NMR (400 MHz, CDCl ) δ 7.83 (1 H, s),
3 H
.35-7.25 (3 H, m), 7.30 (1 H, s), 7.23-7.13 (3 H, m), 7.03-7.02
(2 H, m), 6.66 (1 H, d, J = 7.7 Hz), 4.37 (2 H, q, J = 7.0 Hz), 2.16
13
(3 H, s), 1.33 (3 H, t, J = 7.1 Hz) ppm; C NMR (100 MHz,
(50% EtOAc/Hexanes) 0.45; IR (CH
2
Cl
2
) νmax 2939, 1731, 1642,
) δ 8.18 (2 H,
-
1
1
CDCl ) δ 160.8, 139.7, 136.8, 136.3, 135.7, 131.2, 129.2, 128.9,
1542, and 754 cm ; H NMR (400 MHz, CDCl
3
H
3
C
1
28.9, 128.0, 128.0, 127.3, 126.6, 65.6, 61.3, 19.2, 14.3 ppm;
s), 7.36-7.28 (4 H, m), 6.97 (2 H, t, J = 7.5 Hz), 6.92 (2 H, d, J =
8.2 Hz), 6.12-6.07 (2 H, m), 5.67-5.60 (2 H, m), 5.08-4.97 (4 H,
m), 4.34 (4 H, q, J = 7.1 Hz), 4.21-4.09 (4 H, m), 3.89 (4 H, t, J =
4.6 Hz), 3.26-3.19 (2 H, m), 3.08-3.01 (2 H, m), 1.34 (6 H, t, J =
+
HRMS (ESI): MNa , found 344.1366. C H N NaO requires
3
General procedure for the synthesis of bis-alcohols 7a-d. To
a mixture of corresponding bis-aldehyde (3 mmol), allyl bromide
19
19
3
2
44.1375.
29
13
7.1 Hz) ppm; C NMR (100 MHz, CDCl ) δ 161.0, 156.0,
3
C
(
7 equiv) in THF (7 mL) were sequentially added sat. NH Cl (18
139.5, 132.9, 130.3, 127.8, 127.6, 127.5, 125.6, 125.6, 121.2,
118.9, 112.0, 69.7, 69.7, 67.6, 61.2, 59.5, 59.5, 37.7, 14.3 ppm;
4
mL) and Zn metal (5 equiv) at rt. The resulting mixture was
stirred at rt for 30 h. After this period, the reaction mixture was
extracted by using ethyl acetate (3 X 7 mL). The combined
organic layers were dried over anhydrous Na SO and the organic
+
HRMS (ESI): MNa , found 667.2863. C H N NaO requires
34
40
6
7
667.2856. Isolated as a mixture of diastereomers (dr = 50:50) and
NMR values given for both isomers.
2
4
phase was concentrated, and the resulting crude reaction mixture
was purified by silica gel column chromatography
Diethyl
1,1'-(((((ethane-1,2-diylbis(oxy))bis(ethane-2,1-
diyl))bis(oxy))bis(2,1-phenylene))bis(but-3-ene-1,1-
29
(EtOAc/hexanes) to give the desired products 7a-d.
diyl))bis(1H-1,2,3-triazole-4-carboxylate) (8c). Following the
general procedure, 8c was obtained after purification by silica gel
column chromatography (EtOAc:Hexanes = 50:50) as a colorless
liquid (141 mg, 82%); Rf (50% EtOAc/Hexanes) 0.45; IR
Compound 7a. Following the general procedure, 7a as a
colorless liquid (885 mg, 72%); R (30% EtOAc/Hexanes) 0.42;
f
-
1 1
IR (CH Cl ) ν 3413, 2937, 1600, 1453 and 751 cm ; H NMR
2
2
max
-
1
1
(
400 MHz, CDCl ) δ 7.32 (2 H, d, J = 7.2 Hz), 7.19 (2 H, t, J =
(CH Cl ) ν 2933, 1737, 1602, 1494, and 754 cm ; H NMR
3
H
2 2 max
7
5
.4 Hz), 6.92 (2 H, t, J = 7.4 Hz), 6.82 (2 H, d, J = 8.1 Hz), 5.87-
.77 (2 H, m), 5.11-5.04 (4 H, m) 4.95 (2 H, br. s), 3.98-3.96 (4
(400 MHz, CDCl ) δ 8.22 (2 H, s), 7.33 (2 H, d, J = 7.5 Hz),
3 H
7.28 (2 H, t, J = 7.8 Hz), 6.96 (2 H, t, J = 7.5 Hz), 6.85 (2 H, d, J

1
6
Tetrahedron
=
8.2 Hz), 6.10 (2 H, t, J = 7.7 Hz), 5.70-5.63 (2 H, m), 5.11-
2,2'-(((1,1'-(((((Ethane-1,2-diylbis(oxy))bis(ethane-2,1-
ACCEPTED MANUSCRIPT
4
.97 (4 H, m), 4.37 (4 H, q, J = 7.1 Hz), 4.14-4.05 (4 H, m), 3.84
diyl))bis(oxy))bis(2,1-phenylene))bis(but-3-ene-1,1-
diyl))bis(1H-1,2,3-triazole-4,1-
(4 H, t, J = 5.5 Hz), 3.77 (4 H, br. s), 3.29-3.21 (2 H, m), 3.09-
13
3
.02 (2 H, m), 1.36 (6 H, t, J = 7.1 Hz) ppm; C NMR (100
diyl))bis(methylene))bis(oxy))dibenzaldehyde (8g). Following
the general procedure, 8g was obtained after purification by silica
gel column chromatography (EtOAc:Hexanes = 50:50) as a
MHz, CDCl ) δ 161.0, 155.9, 139.4, 133.0, 130.2, 127.8, 127.8,
3
C
1
25.9, 121.2, 118.9, 112.0, 70.7, 69.4, 67.5, 61.1, 59.6, 37.7, 14.3
+
ppm; HRMS (ESI): MNa , found 711.3135. C H N NaO
colorless liquid (163 mg, 81%); R (50% EtOAc/Hexanes) 0.42;
36
44
6
8
f
-
1 1
requires 711.3118. Isolated as a mixture of diastereomers (dr =
0:50) and NMR values given for both isomers.
IR (CH Cl ) ν 2875, 1687, 1599, 1493 and 756 cm ; H NMR
(400 MHz, CDCl ) δ 10.39 (2 H, s), 7.82 (2 H, s), 7.77-7.75 (2
3 H
2 2 max
5
Diethyl 1,1'-((((1,3-phenylenebis(methylene))bis(oxy))bis(2,1-
phenylene))bis(but-3-ene-1,1-diyl))bis(1H-1,2,3-triazole-4-
carboxylate) (8d). Following the general procedure, 8d was
obtained after purification by silica gel column chromatography
H, m), 7.50-7.46 (2 H, m), 7.28-7.21 (4 H, m), 7.12 (2 H, d, J =
8.4 Hz), 7.00-6.90 (4 H, m), 6.81 (2 H, d, J = 8.1 Hz), 6.06 (2 H,
t, J = 6.8 Hz), 5.69-5.62 (2 H, m), 5.25 (4 H, s), 5.07-4.93 (4 H,
m), 4.10-4.00 (4 H, m), 3.78-3.76 (4 H, m), 3.69 (4 H, br. s),
13
(EtOAc:Hexanes = 50:50) as a colorless liquid (147 mg, 87%); Rf
3.25-3.18 (2 H, m), 3.04-3.00 (2 H, m) ppm; C NMR (100
(
1
50% EtOAc/Hexanes) 0.42; IR (CH Cl ) ν 2982, 1732, 1493,
MHz, CDCl ) δ 189.7, 160.6, 155.7, 142.4, 136.0, 133.4, 129.9,
2
2
max
3
C
-
1 1
227, 1041 and 754 cm ; H NMR (400 MHz, CDCl ) δ 7.90 (2
128.4, 127.7, 126.6, 125.0, 123.3, 121.2, 121.2, 118.5, 113.2,
112.0, 70.6, 69.5, 67.6, 62.6, 59.2, 37.9 ppm; HRMS (ESI):
3
H
H, s), 7.44 (4 H, s), 7.37-7.28 (4 H, m), 7.04-6.91 (4 H, m), 6.10-
.05 (2 H, m), 5.65-5.58 (2 H, m), 5.06-4.95 (8 H, m), 4.41-4.35
4 H, m), 3.21-3.12 (2 H, m), 3.10-2.95 (2 H, m), 1.40-1.38 (6 H,
+
6
(
MNa , found 835.3456. C H N NaO requires 835.3431.
46
48
6
8
Isolated as a mixture of diastereomers (dr = 50:50) and NMR
values given for both isomers.
13
m) ppm; C NMR (100 MHz, CDCl ) δC 160.9, 155.7, 155.7,
3
1
1
1
39.5, 134.5, 134.4, 132.6, 132.6, 130.4, 129.8, 129.7, 129.1,
27.7, 127.6, 127.2, 127.2, 125.7, 125.6, 121.5, 121.5, 119.1,
2,2'-(((1,1'-((((1,3-Phenylenebis(methylene))bis(oxy))bis(2,1-
phenylene))bis(but-3-ene-1,1-diyl))bis(1H-1,2,3-triazole-4,1-
diyl))bis(methylene))bis(oxy))dibenzaldehyde (8h): Following
the general procedure, 8h was obtained after purification by silica
gel column chromatography (EtOAc:Hexanes = 50:50) as a
19.1, 112.3, 112.2, 68.2, 68.1, 61.2, 59.0, 58.8, 38.1, 14.3 ppm;
+
HRMS (ESI): MNa , found 699.2918. C H N NaO requires
38
40
6
6
6
99.2907. Isolated as a mixture of diastereomers (dr = 50:50) and
NMR values given for both isomers.
,2'-(((1,1'-(((Hexane-1,6-diylbis(oxy))bis(2,1-
colorless liquid (312 mg, 78%); R (50% EtOAc/Hexanes) 0.42;
f
-
1 1
2
IR (CH
(400 MHz, CDCl
J = 0.9 Hz), 7.62 (2 H, s), 7.51 (2 H, td, J = 7.8 Hz, J = 1.7 Hz),
2
Cl
2
) νmax 2976, 1686, 1462, 1194 and 751 cm ; H NMR
phenylene))bis(but-3-ene-1,1-diyl))bis(1H-1,2,3-triazole-4,1-
diyl))bis(methylene))bis(oxy))dibenzaldehyde (8e). Following
the general procedure, 8e was obtained after purification by silica
gel column chromatography (EtOAc:Hexanes = 50:50) as a
colorless liquid (131 mg, 68%); R (50% EtOAc/Hexanes) 0.42;
IR (CH Cl ) ν 2940, 1687, 1599, 1456 and 752 cm ; H NMR
3
) δ 10.37 (2 H, s), 7.79 (2 H, dd, J = 7.4 Hz,
H
1
2
1
2
7.37-7.26 (8 H, m), 7.10 (2 H, d, J = 8.4 Hz), 7.03-6.96 (6 H, m),
6.16-6.12 (2 H, m), 5.73-5.62 (2 H, m), 5.24 (4 H, s), 5.12-4.97
1
3
(8 H, m), 3.26-3.18 (2 H, m), 3.07-3.00 (2 H, m) ppm; C NMR
f
-
1 1
(100 MHz, CDCl ) δ 189.6, 160.5, 155.6, 142.5, 137.0, 136.0,
2
2
max
3
C
(
400 MHz, CDCl ) δ 10.42 (2 H, s), 7.80 (2 H, dd, J = 5.8 Hz,
133.2, 130.0, 129.1, 128.5, 127.6, 127.1, 126.5, 126.2, 125.0,
123.0, 121.3, 121.2, 118.7, 113.1, 112.2, 70.0, 62.6, 58.9, 38.3
3
H
1
J2 = 1.8 Hz), 7.65 (2 H, s), 7.52 (2 H, t, J = 8.8 Hz), 7.31-7.26 (4
H, m), 7.13 (2 H, d, J = 8.4 Hz), 7.02 (2 H, t, J = 7.4 Hz), 6.95 (2
H, t, J = 8.2 Hz), 6.89 (2 H, d, J = 8.0 Hz), 6.11 (2 H, t, J = 8.7
Hz), 5.75-5.65 (2 H, m), 5.29 (4 H, s), 5.10-4.99 (4 H, m), 4.00-
+
ppm; HRMS (ESI): MNa , found 823.3250. C H N NaO
48
44
6
6
requires 823.3220. Isolated as a mixture of diastereomers (dr =
50:50) and NMR values given for both isomers.
30
3
.93 (4 H, m), 3.25-3.18 (2 H, m), 3.06-2.99 (2 H, m), 1.80-1.77
Preparation of the compound 10. A solution of (E)-4-phenyl-
1-(3-phenyl-1-(p-tolyl)allyl)-1H-1,2,3-triazole (4o) in MeI (5
mL) was refluxed for 5 d. After this period, excess of MeI was
removed under vacuum and the resulting crude reaction mixture
was washed with Hexanes and ether which gave the compound
10.
13
(4 H, m), 1.49-1.47 (4 H, m) ppm; C NMR (100 MHz, CDCl3)
δC 189.6, 160.6, 156.0, 142.5, 136.0, 133.3, 129.9, 128.5, 127.4,
1
5
26.2, 125.0, 122.8, 121.2, 120.7, 118.5, 113.1, 111.6, 67.9, 62.7,
+
9.0, 38.3, 29.1, 25.8 ppm; HRMS (ESI): MNa , found 803.3548.
C H N NaO requires 803.3533. Isolated as a mixture of
46
48
6
6
diastereomers (dr = 50:50) and NMR values given for both
isomers.
1-(1,3-Diphenylpropyl)-4-phenyl-1H-1,2,3-triazole (11). To
the solution of (E)-1-(1,3-diphenylallyl)-4-phenyl-1H-1,2,3-
triazole (4c, 1 mmol) in THF (2 mL) was added Pd/C (10 mol%).
The reaction mixture was stirred at room temperature for 24 h,
under H2 atm (1 atm). After completion of the reaction, the
reaction mixture was filtered by using a layer of celite pad and
the filtrate was evaporated under vacuum and the resulting crude
reaction mixture was purified by silica gel column
chromatography (EtOAc : Hexanes = 30 : 70) which gave the
2
,2'-(((1,1'-((((Oxybis(ethane-2,1-diyl))bis(oxy))bis(2,1-
phenylene))bis(but-3-ene-1,1-diyl))bis(1H-1,2,3-triazole-4,1-
diyl))bis(methylene))bis(oxy))dibenzaldehyde (8f): Following
the general procedure, 8f was obtained after purification by silica
gel column chromatography (EtOAc:Hexanes = 50:50) as a
colorless liquid (299 mg, 78%); R (50% EtOAc/Hexanes) 0.42;
f
-
1 1
IR (CH Cl ) ν 2976, 1686, 1599, 1483and 756 cm ; H NMR
2
2
max
(
400 MHz, CDCl ) δ 10.41 (2 H, s), 7.79 (2 H, dd, J = 7.6 Hz,
compound 11 as a colorless solid (311 mg, 91%); R (30%
3
H
1
f
J = 1.1 Hz), 7.73 (2 H, s), 7.52 (2 H, td, J = 7.8 Hz, J = 1.2 Hz),
EtOAc/Hexanes) 0.42; mp 110-112 °C; IR (thin film) ν 3062,
2
1
2
max
-
1 1
7
.30-7.24 (4 H, m), 7.10 (2 H, d, J = 8.4 Hz), 7.02 (2 H, t, J = 7.6
Hz), 6.96 (2 H, t, J = 7.5 Hz), 6.85 (2 H, d, J = 8.2 Hz), 6.10-6.06
2 H, m), 5.69-5.62 (2 H, m), 5.22 (4 H, d, J = 3.9 Hz), 5.05 (2 H,
d, J = 17.1 Hz), 4.96 (2 H, d, J = 10.2 Hz), 4.17-4.06 (4 H, m),
3028, 1603, 1454 and 767 cm ; H NMR (400 MHz, CDCl ) δ
3 H
7.84 (2 H, d, J = 7.1 Hz), 7.71 (1 H, s), 7.45-7.22 (11 H, m), 7.19
(2 H, d, J = 7.1 Hz), 5.61 (1 H, dd, J = 9.2 Hz, J = 6.2 Hz), 2.95-
(
1
2
13
2.88 (1 H, m), 2.70-2.66 (3 H, m) ppm; C NMR (100 MHz,
3
.88-3.84 (4 H, m), 3.25-3.17 (2 H, m), 3.07-3.02 (2 H, m) ppm;
CDCl ) δ 147.8,140.3, 138.8, 130.6, 129.1, 128.8, 128.7, 128.7,
3
C
13
C NMR (100 MHz, CDCl ) δC 189.7, 160.5, 155.8, 142.5,
128.5, 128.2, 127.0, 126.4, 125.7, 118.8, 64.4, 36.6, 32.3 ppm;
3
+
1
1
36.0, 133.3, 130.0, 128.5, 127.7, 126.5, 125.0, 122.9, 121.3,
HRMS (ESI): MH , found 340.1806. C H N
3
requires
23
22
21.2, 118.5, 113.1, 112.0, 69.7, 67.7, 62.7, 62.7, 59.1, 59.0, 38.0
340.1814.
+
ppm; HRMS (ESI): MNa , found 791.3150. C H N NaO
Preparation of the compound 12. A solution of (1-(1,3-
diphenylpropyl)-4-phenyl-1H-1,2,3-triazole (11, 0.25 mmol) in
MeI (5 mL) was refluxed for 4 d. After this period, excess of MeI
44
44
6
7
requires 791.3169. Isolated as a mixture of diastereomers (dr =
0:50) and NMR values given for both isomers.
5

1
7
was removed under vacuum and the resulting crude reaction
mixture was washed with Hexanes and ether which gave the
compound 12 as a semi solid (110 mg, 92%); Rf (30%
H, t, J = 4.8 Hz), 3.69 (4 H, br. s), 3.25-3.19 (2 H, m), 3.08-
ACCEPTED MANUSCRIPT
13
3.03 (2 H, m) ppm; C NMR (100 MHz, CDCl ) δ 156.1, 155.8,
143.1, 133.4, 130.0, 129.9, 128.9, 128.7, 127.9, 126.5, 122.9,
121.3, 121.2, 118.5, 112.0, 112.0, 70.6, 69.5, 67.5, 62.4, 61.1,
3
C
EtOAc/Hexanes) 0.42; IR (thin film) ν
2928, 1603, 1494,
max
-
1
1
+
1
454, 1384 and 770 cm ; H NMR (400 MHz, CDCl ) δ 9.45 (1
59.2, 37.9 ppm; HRMS (ESI): MNa , found 839.3761.
3
H
H, s), 7.72 (2 H, d, J = 8.0 Hz), 7.61 (2 H, d, J = 8.0 Hz), 7.53-
C H N NaO requires 839.3744. The OH protons could not be
46
52
6
8
7
7
.45 (3 H, m), 7.42-7.37 (3 H, m), 7.18 (4 H, d, J = 4.3 Hz), 7.13-
.08 (1 H, m), 6.54 (1 H, t, J = 7.6 Hz), 4.20 (3 H, s), 3.12-3.03
detected.
Compound 14c: Following the general procedure, 14c was
obtained after purification by silica gel column chromatography
(EtOAc:Hexanes = 60:40) as a colorless liquid (739 mg, 92%); Rf
(60% EtOAc/Hexanes) 0.42; IR (CH Cl ) ν 3345, 1601, 1492,
13
(
1 H, m), 2.81-2.69 (3 H, m) ppm; C NMR (100 MHz, CDCl3)
δC 142.8, 139.7, 135.5, 132.0, 130.0, 129.7, 129.5, 129.5, 128.9,
28.6, 128.4, 128.2, 126.3, 121.5, 68.9, 39.7, 35.6, 32.3 ppm;
1
2
2
max
+
-1 1
HRMS (ESI): M-IH , found 355.1996. C H N requires
1243 and 755 cm ; H NMR (400 MHz, CDCl ) δ 7.52 (2 H, s),
24
25
3
3 H
3
55.2048.
7.41 (2 H, t, J = 8.2 Hz), 7.30 (8 H, m), 7.22 (2 H, t, J = 8.0 Hz),
7.01-6.92 (8 H, m), 6.13-6.09 (2 H, m), 5.72-5.62 (2 H, m), 5.15-
4.98 (12 H, m), 4.62 (4 H, s), 3.25-3.18 (2 H, m), 3.07-3.00 (2 H,
Preparation of the compound 13. To a solution of (E)-(3-
azidoprop-1-ene-1,3-diyl)dibenzene (2, 1 mmol) in THF (2 mL)
was added Pd/C (10 mol%). The reaction mixture was stirred at
room temperature for 24 h under H2 atm (1 atm). After
completion of the reaction, the reaction mixture was filtered by
using a layer of celite pad and the filtrate was evaporated under
vacuum and the resulting crude reaction mixture was transferred
into a separating funnel with DCM and extracted twice with 1 N
HCl (4 mL). The acidic aqueous layer was washed 2 times with
EtOAc (5 mL). The aqueous phase was then made basic (pH: 10-
13
m) ppm; C NMR (100 MHz, CDCl ) δ 156.1, 155.6, 143.2,
3
C
137.0, 133.2, 130.0, 129.9, 129.1, 128.9, 128.8, 127.6, 127.1,
127.1, 126.6, 126.6, 126.3, 126.3, 122.6, 122.6, 121.4, 118.6,
112.2, 112.0, 70.0, 62.4, 61.4, 58.9, 58.9, 38.2 ppm; HRMS
+
(ESI): MH , found 805.3755. C H N O requires 805.3714. The
48
49
6
6
OH protons could not be detected.
Procedure for the syntheses of compounds 15. To a mixture of
the diol compound 14 (0.5 mmol) in dry THF (3 mL) was added
NaH (4 mmol, 55-60 % suspension in mineral oil) at rt. The
mixture was stirred at room temperature for 10 min and then,
propargyl bromide (5 mmol, 80 wt% in toluene) was added. The
resulting mixture was stirred for 20 h at rt. After this period, few
drops of EtOH was added and stirred for 10 min and then, the
resulting mixture was poured on to water (20 mL) and was
extracted by using ethyl acetate (3 X 10 mL).The combined
organic layers were dried over anhydrous Na SO and the organic
1
1) with 2 N NaOH and extracted with DCM (5 mL). The
combined organic layers were dried over anhydrous Na SO and
the organic phase was concentrated to afford the compound 13 as
colorless liquid (105 mg, 50%); IR (Thin film) ν 3026, 1602,
1
2
4
max
-
1
1
453 and 1029 cm ; H NMR (400 MHz, CDCl ) δ 7.39-7.18
3 H
(10 H, m), 3.93 (1 H, t, J = 6.8 Hz), 2.70-2.55 (2 H, m), 2.07-2.01
13
(2 H, m), 1.73 (2 H, s) ppm; C NMR (100 MHz, CDCl ) δ
3
C
1
46.2, 141.9, 128.6, 128.4, 127.1, 126.4, 125.8, 55.8, 41.0, 32.8
2
4
+
ppm; HRMS (ESI): MH , found 212.1441. C H N requires
2
Procedure forthe synthesis of bis-alcohol 14. NaBH (4 mmol)
phase was concentrated, and the resulting crude reaction mixture
was purified by silica gel column chromatography (EtOAc/
Hexanes) to give the desired product 15.
15
18
12.1439.
4
was added to a mixture of bis-aldehyde 8 (1 mmol) in THF (3
mL) and ethanol (7 mL) at room temperature. The resulting
mixture was stirred at room temperature for 1 h. After this
period, the reaction mixture was poured on to cold water (5 mL).
Then, extracted by using ethyl acetate (3 X 10 mL) and the
combined organic layers were dried over anhydrous Na SO and
Compound 15a: Following the general procedure, 15a was
obtained after purification by silica gel column chromatography
as colorless liquid (254 mg, 60%); R (40% EtOAc/Hexanes)
f
-
1 1
0.42; IR (CH Cl ) ν 3288, 2976, 1602, 1455 and 755 cm ; H
2
2
max
NMR (400 MHz, CDCl ) δ 7.68 (2 H, s), 7.36 (2 H, dd, J = 7.8
3
H
1
Hz, J = 1.4 Hz), 7.29-7.24 (6 H, m), 6.99-6.95 (6 H, m), 6.86 (2
2
4
2
the organic phase was concentrated and the resulting crude
reaction mixture was purified by silica gel column
H, d, J = 8.6 Hz), 6.11-6.06 (2 H, m), 5.71-5.64 (2 H, m), 5.18 (4
H, s), 5.07 (2 H, d, J = 17.1 Hz), 4.99 (2 H, d, J = 10.1 Hz), 4.61
(4 H, s), 4.16-4.08 (8 H, m), 3.88-3.84 (4 H, m), 3.22-3.17 (2 H,
chromatography (EtOAc
: Hexanes) to give the desired
13
compound 14.
m), 3.07-2.99 (2 H, m), 2.37 (2 H, m) ppm; C NMR (100 MHz,
Compound 14a: Following the general procedure, 14a was
CDCl ) δ 156.1, 155.7, 143.6, 133.4, 129.9, 129.8, 129.2, 127.6,
3
C
obtained after purification by silica gel column chromatography
126.7, 126.1, 122.6, 122.6, 121.2, 121.1, 118.4, 112.1, 112.0,
80.0, 74.5, 69.8, 67.8, 66.7, 62.6, 58.9, 57.4, 38.1 ppm; HRMS
(EtOAc:Hexanes = 60:40) as a colorless liquid (741 mg, 96%); Rf
+
(
60% EtOAc/Hexanes) 0.42; IR (CH Cl ) ν 3402, 2936, 1601,
(ESI): MH , found 849.3996. C H N O requires 849.3976.
2
2
max
50 53
6
7
-
1 1
1
7
6
455and 754 cm ; H NMR (400 MHz, CDCl ) δ 7.65 (2 H, s),
Compound 15b: Following the general procedure, 15b was
obtained after purification by silica gel column chromatography
3
H
.31-7.20 (8 H, m), 6.99-6.89 (6 H, m), 6.84 (2 H, d, J = 8.2 Hz),
.05-6.01 (2 H, m), 5.69-5.62 (2 H, m), 5.10-4.96 (8 H, m), 4.62
as colorless liquid (379 mg, 85%); R (40% EtOAc/Hexanes)
f
-
(
4 H, s), 4.15-4.03 (4 H, m), 3.85-3.80 (4 H, m), 3.23-3.19 (2 H,
0.42; IR (CH Cl ) ν 2875, 1602, 1493, 1454, 1247 and 755 cm
2
2
max
13
1 1
m), 3.05-3.02 (2 H, m) ppm; C NMR (100 MHz, CDCl ) δ
; H NMR (400 MHz, CDCl ) δ 7.73 (2 H, s), 7.37 (2 H, dd, J
3
C
3
H
1
1
1
1
56.1, 155.9, 155.8, 143.2, 143.2, 133.3, 133.3, 130.0, 129.9,
29.0, 129.0, 128.8, 127.8, 127.8, 126.4, 126.4, 122.7, 122.6,
= 7.4 Hz, J = 1.5 Hz), 7.29-7.24 (6 H, m), 7.00-6.94 (6 H, m),
2
6.85 (2 H, d, J = 8.2 Hz), 6.11-6.07 (2 H, m), 5.73-5.67 (2 H, m),
5.21 (4 H, s), 5.11-5.98 (4 H, m), 4.61 (4 H, s), 4.14-4.03 (8 H,
m), 3.79 (4 H, t, J = 4.8 Hz), 3.71 (4 H, s), 3.24-3.19 (2 H, m),
21.3, 121.3, 118.5, 112.0, 69.8, 67.7, 62.3, 61.3, 59.1, 37.9, 37.8
+
ppm; HRMS (ESI): MNa , found 795.3467. C H N NaO
requires 795.3482. The OH protons could not be detected.
Compound 14b: Following the general procedure, 14b was
44
48
6
7
13
3.07-2.99 (2 H, m), 2.38 (2 H, t, J = 2.4 Hz) ppm; C NMR (100
MHz, CDCl ) δ 156.1, 155.7, 143.5, 133.5, 129.8, 129.7, 129.2,
3
C
obtained after purification by silica gel column chromatography
127.6, 126.9, 126.1, 122.9, 121.2, 121.1, 118.4, 112.1, 112.0,
80.0, 74.5, 70.7, 69.6, 67.6, 66.7, 62.6, 59.0, 57.4, 38.1 ppm;
(EtOAc:Hexanes = 50:50) as a colorless liquid (709 mg, 95%); Rf
+
(
1
60% EtOAc/Hexanes) 0.42; IR (CH Cl ) ν 3412, 2876, 1589,
HRMS (ESI): MH , found 893.4271. C H N O requires
2
2
max
52 57
6
8
-
1 1
602, 1454 and 754 cm ; H NMR (400 MHz, CDCl ) δ 7.75 (2
893.4238.
3
H
H, s), 7.32-7.19 (8 H, m), 6.98-6.91 (6 H, m), 6.83 (2 H, d, J =
.2 Hz), 6.05 (2 H, t, J = 7.7 Hz), 5.71-5.64 (2 H, m), 5.16 (4 H,
s), 5.10-4.97 (4 H, m), 4.63 (4 H, s), 4.08-3.98 (4 H, m), 3.75 (4
Compound 15c: Following the general procedure, 15c was
obtained after purification by silica gel column chromatography
8
as colorless liquid (352 mg, 80%); R (40% EtOAc/Hexanes)
f

1
8
Tetrahedron
-1
+
0
.42; IR (CH Cl ) ν 2973, 1603, 1461, 1249 and 669 cm ;
57.9, 38.0, 38.0 ppm; HRMS (ESI): MH , found 879.3891.
2
2
max
ACCEPTED MANUSCRIPT
1
H NMR (400 MHz, CDCl ) δ 7.58 (2 H, s), 7.43-7.23 (12 H,
C H N O requires 879.3870.
3
H
54 51 6 6
29b
m), 7.01-6.95 (8 H, m), 6.14 (2 H, t, J = 7.1 Hz), 5.74-5.64 (2 H,
m), 5.20 (4 H, m), 5.13-4.99 (8 H, m), 4.60 (4 H, s), 4.12-4.10 (4
H, m), 3.26-3.18 (2 H, m), 3.07-3.00 (2 H, m), 2.31 (2 H, t, J =
Procedure for the synthesis of macrocycle 17. A mixture of
16 (0.1 mmol), Na S.xH O (70 mg), CuI (10 mol%), 1,10-phen
2
2
o
(15 mol%) in DMF (0.5 mL) was stirred at 90 C for 12 h under
open air atmosphere. After this period, the reaction mixture was
cooled to room temperature. Then, the resulting mixture was
diluted with water (4 mL). The mixture was filtered through a
filtration funnel and then washed with ethyl acetate (4 times,
using 5 mL of EtOAc) and extracted using ethyl acetate (3 X 5
mL) and the combined organic layers were dried over anhydrous
Na SO . The solvent was removed under reduced pressure and
13
2
1
1
7
.3) ppm; C NMR (100 MHz, CDCl ) δ 156.1, 155.5, 143.6,
37.0, 133.3, 129.9, 129.8, 129.2, 129.1, 127.5, 127.1, 126.8,
26.2, 126.1, 122.6, 121.3, 121.1, 118.6, 112.2, 112.1, 80.0, 74.5,
3 C
+
0.0, 66.7, 62.7, 58.8, 57.4, 38.4 ppm; HRMS (ESI): MNa ,
found 903.3871. C H N NaO requires 903.3846.
Procedure
polyether 16. A mixture of 15 (0.5 mmol), Cu(OAc) H O (100
54
52
6
6
29b
for the synthesis of macrocyclic bis-triazole
2
˙
2
2
4
mol%) and DMSO (2 mL) was taken in a 10 ml round bottom
flask. The reaction mixture was stirred at 110 °C under open air
atmosphere for 12 h. After this period, the resulting mixture was
cooled to rt and diluted with water (4 mL). The mixture was
filtered through a filtration funnel and then washed with ethyl
acetate (4 times, using 5 mL of EtOAc) and extracted using
EtOAc (3 X 5 mL) and the combined organic layers were dried
over anhydrous Na SO . The solvent was removed under reduced
the residue was purified by silica gel chromatography
(EtOAc/Hexanes) which gave the desired macrocyclic polyether
17.
Compound 17a: Following the general procedure, 17a was
obtained after purification by silica gel column chromatography
as yellow color liquid (39 mg, 45%); R (40% EtOAc/Hexanes)
f
-
1 1
0.42; IR (CH Cl ) ν 2975, 1721, 1602, 1457 and 755 cm ; H
2
2
max
NMR (400 MHz, CDCl ) δ 7.69 (2 H, s), 7.40-7.33 (4 H, m),
2
4
3
H
pressure and the residue was purified by silica gel
chromatography (EtOAc/Hexanes) which gave the macrocyclic
bis-triazole polyether 16.
Compound 16a: Following the general procedure, 16a was
obtained after purification by silica gel column chromatography
7.26-7.20 (4 H, m), 7.00-6.94 (6 H, m), 6.76-6.74 (4 H, m), 5.99-
5.93 (2 H, m), 5.69-5.60 (2 H, m), 5.18 (4 H, br. s), 5.08-4.94 (4
H, m), 4.60 (4 H, d, J = 4.8 Hz), 4.56 (4 H, d, J = 4.7 Hz), 4.06-
3.93 (4 H, m), 3.74-3.65 (4 H, m), 3.29-3.23 (2 H, m), 3.08-3.01
13
(2 H, m) ppm; C NMR (100 MHz, CDCl ) δ 156.1, 155.8,
3
C
as colorless liquid (194 mg, 46%); R (40% EtOAc/Hexanes)
155.8, 143.4, 141.7, 133.5, 129.9, 129.6, 129.0, 128.2, 128.1,
126.5, 126.4, 125.9, 123.0, 121.2, 121.0, 118.4, 111.9, 69.6, 69.5,
67.5, 67.5, 67.0, 67.0, 66.9, 66.9, 62.6, 62.6, 59.5, 59.3, 37.7,
f
-
1 1
0
.42; IR (CH Cl ) ν 2973, 1601, 1459, 1368 and 754 cm ; H
2 2 max
NMR (400 MHz, CDCl ) δ 7.79 (2 H, s), 7.38 (2 H, dt, J = 7.7
3
H
1
+
Hz, J = 1.9 Hz), 7.33 (2 H, dd, J = 7.3 Hz, J = 1.6 Hz), 7.29-
37.7 ppm; HRMS (ESI): MNa , found 903.3545. C H N NaO S
2
1
2
50 52
6
7
7
(
5
.22 (4 H, m), 7.00-6.95 (6 H, m), 6.82-6.79 (2 H, m), 6.04-5.99
2 H, m), 5.70-5.63 (2 H, m), 5.22-5.15 (4 H, m), 5.07 (2 H, m),
.00-4.96 (2 H, m), 4.60 (4 H, s), 4.23 (4 H, s), 4.16-4.06 (4 H,
m), 3.88-3.81 (4 H, m), 3.31-3.28 (2 H, m), 3.10-3.05 (2 H, m)
requires 903.3516.
Compound 17b: Following the general procedure, 17b was
obtained after purification by silica gel column chromatography
as yellow color liquid (66 mg, 72%); R (40% EtOAc/Hexanes)
f
13
-
ppm; C NMR (100 MHz, CDCl ) δ 156.0, 155.9, 143.4, 133.4,
0.42; IR (CH Cl ) ν 2926, 1600, 1493, 1454, 1247 and 754 cm
3
C
2
2
max
1
1
1
1
6
30.0, 129.2, 129.2, 128.2, 128.2, 126.5, 125.8, 123.1, 123.0,
21.2, 121.0, 118.4, 112.0, 111.9, 76.0, 70.3, 69.7, 69.7, 67.6,
; H NMR (400 MHz, CDCl ) δ 7.77 (2 H, s), 7.39 (2 H, d, J =
3 H
7.4 Hz), 7.31 (2 H, dt, J = 7.7 Hz, J = 1.8 Hz), 7.27-7.23 (4 H,
1
2
+
7.6, 67.1, 62.7, 62.6, 59.3, 58.1, 37.7 ppm; HRMS (ESI): MH ,
m), 7.01-6.94 (6 H, m), 6.79 (2 H, d, J = 8.7 Hz), 6.78 (1 H, s),
6.76 (1 H, s), 5.99 (2 H, t, J = 8.2 Hz), 5.70-5.62 (2 H, m), 5.20
(4 H, br. s), 5.08-4.96 (4 H, m), 4.62 (4 H, s), 4.58 (4 H, s), 4.02-
3.94 (4 H, m), 3.67-3.64 (4 H, m), 3.59 (4 H, s), 3.29-3.24 (2 H,
found 847.3850. C H N O requires 847.3819.
Compound 16b: Following the general procedure, 16b was
obtained after purification by silica gel column chromatography
as colorless liquid (259 mg, 57%); R (40% EtOAc/Hexanes)
50
51
6
7
13
m), 3.08-3.04 (2 H, m) ppm; C NMR (100 MHz, CDCl ) δC
f
3
-
0
.42; IR (CH Cl ) ν 2926, 1603, 1493, 1454, 1247 and 754 cm
H NMR (400 MHz, CDCl ) δ 7.88 (2 H, s), 7.38-7.24 (8 H,
156.1, 155.7, 143.4, 141.7, 133.5, 129.8, 129.5, 128.9, 128.1,
128.0, 126.9, 126.8, 126.7, 125.9, 123.4, 123.4, 121.2, 121.2,
121.0, 118.4, 112.0, 111.9, 70.6, 70.5, 69.4, 67.5, 67.5, 67.0,
2
2
max
1
1
;
3 H
m), 7.03-6.95 (6 H, m), 6.81 (2 H, d, J = 8.2 Hz), 6.05-6.01 (2 H,
m), 5.74-5.64 (2 H, m), 5.22 (4 H, t, J = 3.6 Hz), 5.11-5.07 (2 H,
m), 5.00-4.98 (2 H, m), 4.61 (4 H, s), 4.24 (4 H, s), 4.05-4.00 (4
H, m), 3.75-3.71 (8 H, m), 3.35-3.27 (2 H, m), 3.12-3.05 (2 H, m)
+
66.9, 66.9, 62.6, 59.4, 59.3, 37.7 ppm; HRMS (ESI): MH , found
925.3987. C H N O S requires 925.3959.
52
57
6
8
Compound 17c: Following the general procedure, 17c was
obtained after purification by silica gel column chromatography
13
ppm; C NMR (100 MHz, CDCl ) δ 156.0, 155.8, 143.3, 133.5,
3
C
1
1
6
29.8, 129.2, 129.2, 128.1, 128.1, 126.8, 126.8, 125.9, 123.5,
21.2, 121.0, 118.4, 111.9, 111.9, 75.9, 70.6, 70.3, 69.5, 67.5,
7.5, 67.1, 62.6, 59.3, 59.3, 58.1, 37.7 ppm; HRMS (ESI): MH ,
as yellow color liquid (62 mg, 69%); R (40% EtOAc/Hexanes)
f
-
1 1
0.42; IR (CH Cl ) ν 2971, 1603, 1495, 1243 and 752 cm ; H
2
2
max
+
NMR (400 MHz, CDCl ) δ 7.47 (2 H, s), 7.38-7.32 (4 H, m),
3 H
found 891.4110. C H N O requires 891.4081. This compound
contains traces of residual DMSO signal.
Compound 16c: Following the general procedure, 16c was
obtained after purification by silica gel column chromatography
7.28-7.20 (8 H, m), 7.00-6.95 (6 H, m), 6.90 (2 H, d, J = 8.3 Hz),
6.65 (1 H, s), 6.60 (1 H, s), 6.63-5.97 (2 H, m), 5.71-5.62 (2 H,
m), 5.23-5.15 (4 H, m), 5.09-4.95 (8 H, m), 4.50-4.67 (8 H, m),
52
55
6
8
13
3.28-3.21 (2 H, m), 3.07-2.99 (2 H, m) ppm; C NMR (100
as colorless liquid (184 mg, 42%); R (40% EtOAc/Hexanes)
MHz, CDCl ) δ 156.0, 155.6, 155.6, 143.5, 143.4, 141.6, 137.0,
f
3
C
-
1 1
0
.42; IR (CH Cl ) ν 2975, 1602, 1493, 1244 and 930 cm ; H
133.4, 129.9, 129.9, 129.5, 129.2, 129.1, 129.0, 127.9, 127.8,
127.2, 126.6, 126.6, 126.6, 126.6, 126.4, 126.3, 125.8, 125.8,
123.1, 123.0, 121.3, 121.3, 121.1, 118.5, 112.1, 111.9, 69.9, 69.9,
66.8, 66.8, 66.7, 62.6, 62.6, 59.2, 58.9, 38.1, 38.0 ppm; HRMS
2
2
max
NMR (400 MHz, CDCl ) δ 7.55 (2 H, s), 7.41-7.26 (12 H, m),
3
H
7
4
.02-6.92 (8 H, m), 6.07-6.02 (2 H, m), 5.73-5.65 (2 H, m), 5.23-
.98 (12 H, m), 4.53 (4 H, s), 4.09-4.06 (4 H, m), 3.32-3.25 (2 H,
13
+
m), 3.09-3.03 (2 H, m) ppm; C NMR (100 MHz, CDCl ) δ
(ESI): MH , found 913.3716. C H N O S requires 913.3747.
3
C
54 53
6
6
1
1
1
1
56.1, 156.0, 155.7, 155.7, 143.4, 143.4, 137.0, 133.4, 133.4,
29.9, 129.5, 129.3, 129.1, 127.9, 127.4, 127.3, 126.6, 126.6,
25.8, 125.8, 123.1, 121.3, 121.1, 118.6, 112.1, 112.1, 111.9,
11.9, 75.8, 75.8, 70.3, 70.1, 70.0, 67.0, 62.7, 62.6, 59.0, 58.9,
Acknowledgments

1
9
2
670. (h) Moses, J. E.; Moorhouse, A. D. Chem. Soc. Rev.
We thank IISER-Mohali for funding th
A
is
C
re
C
se
E
arc
P
h
TED
w
o
rk MANUSCRIPT
2007, 36, 1249. (i) Thirumurugan, P.; Matosiuk, D.; Jozwiak, K.
and NMR, HRMS and X-ray facilities. Naveen and N. A.
Chem. Rev. 2013, 113, 4905. (j) Agalave, S. G.; Maujan, S. R.;
Pore, V. S. Chem. Asian J. 2011, 6, 2696. (k) Lutz, J.-F. Angew.
Chem. Int. Ed. 2007, 46, 1018. (l) Liu, D.; Zheng, Y.; Steffen, W.;
Wagner, M.; Butt, H.-J.; Ikeda, T. Macromol. Chem. Phys. 2013,
Aslam thank UGC, New Delhi, for the SRF fellowships
.
References and notes
2
14, 56. (m) Jiang, L.; Wang, Z.; Bai, S.-Q.; Hor, T. S. A. Dalton
1
.
For selected articles/reviews dealing on the reactions of
Trans. 2013, 42, 9437.
allylic/benzylic and other alcohols, see: (a) Sanz, R.; Martínez, A.;
Miguel, D.; Álvarez-Gutiérrez, J. M.; Rodríguez, F. Adv. Synth.
Catal. 2006, 348, 1841. (b) Trillo, P.; Baeza, A.; Nájera, C. Eur. J.
Org. Chem. 2012, 2929. (c) Tamaru, Y. Eur. J. Org. Chem. 2005,
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13. Alvarez, S. G.; Alvarez, M. T. Synthesis 1997, 413.
14. For selected articles dealing on the Mitsunobu reactions of
alcohols, see: (a) Hughes, D. L. Org. Prep. Proced. Int. 1996, 28,
127. (b) Mitsunobu, O.; Wada, M.; Sano, T. J. Am. Chem. Soc.
1972, 94, 679. (c) Viaud, M. C.; Rollin, P. Synthesis 1990, 130.
15. For selected articles dealing on the conversion of alcohols into
azides under Mitsunobu-type reaction, see: (a) Thompson, A. S.;
Humphrey, G. R.; DeMarco, A. M.; Mathre, D. J.; Grabowski, E.
J. J. J. Org. Chem. 1993, 58, 5886. (b) Lee, J.; Lee, J.; Kang, M.;
Shin, M.; Kim, J.-M.; Kang, S.-U.; Lim, J.-O.; Choi, H.-K.; Suh,
Y.-G.; Park, H.-G.; Oh, U.; Kim, H.-D.; Park, Y.-H.; Ha, H.-J.;
Kim, Y.-H.; Toth, A.; Wang, Y.; Tran, R.; Pearce, L. V.;
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(c) Lal, B.; Pramanik, B. N.; Manhas, M. S.; Bose, A. K.
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Lett. 1997, 38, 3955. (f) Mizuno, M.; Shioiri, T. Chem. Commun.
1997, 2165. (g) Rokhum, L.; Bez, G. J. Chem. Sci. 2012, 124, 687.
16. For examples of the direct azidation of allylic and benzylic
2
647.
2
3
.
.
Emer E.; Sinisi, R.; Capdevila, M. G.; Petruzziello, D.; De
Vincentiis, F.; Cozzi, P. G. Eur. J. Org. Chem. 2011, 647.
For selected articles/reviews dealing on the reactions of
allylic/benzylic and other alcohols, see: (a) Bandini, M. Angew.
Chem. Int. Ed. 2011, 50, 994. (b) Kumar, R.; Van der Eycken, E.
V. Chem. Soc. Rev. 2013, 42, 1121.
4
.
For selected articles dealing on the reactions of allylic/benzylic
and other alcohols, see: (a) Shirakawa, S.; Shimizu, S. Synlett
2
2
5
008, 1539. (b) Trillo, P.; Baeza, A.; Nájera, C. J. Org. Chem.
012, 77, 7344. (c) Srinu, G.; Srihari, P. Tetrahedron Lett. 2013,
4, 2382. (d) Reddy, P. S.; Ravi, V.; Sreedhar, B. Tetrahedron
Lett. 2010, 51, 4037 and references cited therein. (e) Srihari, P.;
Bhunia, D. C.; Sreedhar, P.; Yadav, J. S. Synlett 2008, 1045. (f)
Wu, W.; Rao, W.; Er, Y. Q.; Loh, J. K.; Poh, C. Y.; Chan, P. W.
H. Tetrahedron. Lett. 2008, 49, 2620. (g) Srihari, P.; Bhunia, D.
C.; Sreedhar, P.; Mandal, S. S.; Reddy, J. S. S.; Yadav, J. S.
Tetrahedron. Lett. 2007, 48, 8120.
3
alcohols with NaN as an azide reagent, see: (a) Sagar Reddy, G.
5
6
.
.
For selected articles dealing on the reactions of allylic/benzylic
and other alcohols, see: (a) Hajipour, A. R.; Rajaei, A.; Ruoho, A.
E. Tetrahedron Lett. 2009, 50, 708. (b) Yadav, J. S.; Bhunia, D.
C.; Krishna, K. V.; Srihari, P. Tetrahedron Lett. 2007, 48, 8306.
V.; Rao, G. V.; Subramanyam, R. V. K.; Iyengar, D. S. Synth.
Commun. 2000, 30, 2233. (b) Soltani Rad, M. N.; Behrouz, S.;
Khalafi-Nezhad, A. Tetrahedron Lett. 2007, 48, 3445. (c) Batool,
A.; Sima, S. J. Braz. Chem. Soc. 2007, 18, 1311. (d) Hajipour, A.
R.; Rajaei, A.; Ruoho, A. E. Tetrahedron. Lett. 2009, 50, 708. (e)
Uozumi, Y.; Suzuka, T.; Kawade, R.; Takenaka, H. Synlett 2006,
(c) Kumar, H.M. S.; Reddy, B.V. S.; Anjaneyulu, S.; Yadav, J. S.
Tetrahedron Lett. 1998, 39, 7385.
5c,6a,b
For selected articles dealing on the reactions of allylic/benzylic
and other alcohols, see: (a) Kitamura, M.; Koga, T.; Yano, M.;
Okauchi, T. Synlett 2012, 23, 1335. (b) Jayanthi, A.; Gumaste, V.
K.; Deshmukh, A. R. A. S. Synlett 2004, 979. (c) Rueping, M.;
Vila, C.; Uria, U. Org. Lett. 2012, 14, 768. (d) Tummatorn, J.;
Thongsornkleeb, C.; Ruchirawat, S.; Thongaram, P.; Kaewmee, B.
Synthesis 2015, 47, 323
2109. (f) see ref.
17. For examples of the direct azidation of allylic and benzylic
alcohols with TMSN as an azide reagent, see: (a) Malkov, A. V.;
3
Spoor, P.; Vinader, V.; Kocovsky, P. J. Org. Chem. 1999, 64,
5308. (b) Rokade, B. V.; Malekar, S. K.; Prabhu, K. R. Chem.
Commun. 2012, 48, 5506. (c) Khedar, P.; Pericherla, K.; Kumar,
4c,6c
A. Synlett 2014, 25, 515. (d) see ref.
(e) Rokade, B. V.; Gadde,
7
8
.
.
For selected articles dealing on the reactions of allylic/benzylic
and other alcohols, see: (a) Muzart, J. Tetrahedron 2005, 61, 4179.
K.; Prabhu, K. R. Eur. J. Org. Chem. 2015, DOI:
10.1002/ejoc.201500010.
(b) Trost, B. M.; Crawley, M. L. Chem. Rev. 2003, 103, 2921.
18. For selected papers dealing on the conversion of allyl esters to
azide in the presence of a palladium catalyst, see: (a) Murahashi,
S.-I.; Taniguchi, Y.; Imada, Y.; Tanigawa, Y. J. Org. Chem. 1989,
54, 3292. (b) Kamijo, S.; Jin, T.; Yamamoto, Y.; Tetrahedron
Lett. 2004, 45, 689. (c) Kamijo, S.; Jin, T.; Huo, Z.; Yamamoto,
Y.; Tetrahedron Lett. 2002, 43, 9707.
For selected articles dealing on the reactions azides, see: (a)
Skoda, E. M.; Davis, G. C.; Wipf, P. Org. Process Res. Dev. 2012,
1
6, 26. (b) Scriven, E. F. V.; Turnbull, K. Chem. Rev. 1988, 88,
2
97. (c) Azides and Nitrenes; E. F. V., Scriven, Ed.; Academic:
New York, NY, 1984.
9
.
Organic azides are a versatile class of compounds and useful
precursors for the preparation of amines, nitrenes and heterocyclic
compounds see: (a) Bräse, S.; Gil, C.; Knepper, K.; Zimmermann,
V. Angew. Chem. Int. Ed. 2005, 44, 5188. (b) Mazal, C.; Jonas, J.;
Žák, Z. Tetrahedron 2002, 58, 2729. (c) Gardiner, M.; Grigg, R.;
Kordes, M.; Sridharan, V.; Vicker, N. Tetrahedron 2001, 57,
19. For papers dealing on the synthesis of 1,2,3-triazoles from organic
halides/amines involving sequential reactions, see: (a)
Appukkuttan, P.; Dehaen, W.; Fokin, V. V.; Van der Eycken, E.
Org. Lett. 2004, 6, 4223. (b) Molander, G. A.; Ham, J. Org. Lett
2006, 8, 2767. (c) Kacprzak, K. Synlett 2005, 943. (d) Beckmann,
H. S. G.; Wittmann, V. Org. Lett 2007, 9, 1. For selected paper
dealing on one-pot multicomponent synthesis of 1,2,3-triazoles,
see: (e) Feldman, A. K.; Colasson, B.; Fokin, V. V. Org. Lett
2004, 6, 3897.
7
729. (d) Salunkhe, A. M.; Ramachandran, P. V.; Brown, H. C.
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(

20
Tetrahedron
supporting information of this reference for the FT-IR spectra
ACCEPTED MANUSCRIPT
and HRTEM analysis images).
4. Magnetic nano Fe used in this work was purchased from
2
3 4
O
Sigma-Aldrich and the size of the nano particles was verified
through HRTEM analysis (see the Supporting Information) before
using the nano Fe
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°
Supplementary data
1
13
Supplementary data (copy of H, C NMR Charts of all the
compounds) associated with this article can be found, in the
online version.

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