Tandem reaction of 1-copper(I) alkynes for the synthesis of 1,4,5-trisubstituted 5-chloro-1,2,3-triazoles

Article abstract of DOI:10.1021/jo401629x

A novel tandem reaction of 1-copper(I) alkynes with azides (cycloaddition) and then NCS (electrophilic substitution) was developed as an efficient method for the synthesis of 1,4,5-trisubstituted 5-chloro-1,2,3-triazoles. The method offers a rare example that a tandem reaction of an organometallic substrate does not involve in the reactivity of the metal-carbon bond in the first step.

Full text of DOI:10.1021/jo401629x

Subscriber access provided by Umea University Library
Note
A Tandem Reaction of 1-Copper(I) Alkynes for the
Synthesis of 1,4,5-Trisubstituted 5-Chloro-1,2,3-Triazoles
Bo Wang, Jianlan Zhang, Xinyan Wang, Nan Liu, Wenwen Chen, and Yuefei Hu
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/jo401629x • Publication Date (Web): 13 Sep 2013
Downloaded from http://pubs.acs.org on September 24, 2013
Just Accepted
“Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted
online prior to technical editing, formatting for publication and author proofing. The American Chemical
Society provides “Just Accepted” as a free service to the research community to expedite the
dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts
appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been
fully peer reviewed, but should not be considered the official version of record. They are accessible to all
readers and citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered
to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published
in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just
Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor
changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers
and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors
or consequences arising from the use of information contained in these “Just Accepted” manuscripts.
The Journal of Organic Chemistry is published by the American Chemical Society.
1155 Sixteenth Street N.W., Washington, DC 20036
Published by American Chemical Society. Copyright © American Chemical Society.
However, no copyright claim is made to original U.S. Government works, or works
produced by employees of any Commonwealth realm Crown government in the course
of their duties.

Page 1 of 16
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
A Tandem Reaction of 1-Copper(I) Alkynes
for the Synthesis of 1,4,5-Trisubstituted 5-Chloro-1,2,3-Triazoles
Bo Wang, Jianlan Zhang, Xinyan Wang,* Nan Liu, Wenwen Chen, Yuefei Hu*
Department of Chemistry, Tsinghua University, Beijing 100084, P. R. China
Fax: +86 10-62771149
E-mail: yfh@mail.tsinghua.edu.cn
wangxinyan@mail.tsinghua.edu.cn
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 2 of 16
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
Graphic Abstract
NIS, 10 min
PhC C-I
98%
BnN , CH Cl , rt NBS, 2 h
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
3
2
2
(
PhC CCu)
(PhC C)2
N
73%
NCS, 5 h
Bn
N
N
8
8%
N
Cl+
BnN3
Bn
N
N
Ph
Cl
cycloaddition
substitution
Ph
[Cu]
20 Examples in 63-93%
Abstract
A novel tandem reaction of 1-copper(I) alkynes with azides (cycloaddition) and then NCS
electrophilic substitution) was developed as an efficient method for the synthesis of 1,4,5-trisubstituted
(
5
-chloro-1,2,3-triazoles. The method offers a rare example that a tandem reaction of an organometallic
substrate does not involve in the reactivity of the metal-carbon bond in the first step.
ACS Paragon Plus Environment

Page 3 of 16
The Journal of Organic Chemistry
The isolated 1-copper(I) alkynes (1) are believed to have the polymeric complex structure as
1
2
1
(
RC≡CCu)
n
, in which the acetylene bond serves as a ligand without any exogenous ligand. For example,
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
∞
the detailed structures of t-BuC≡CCu and PhC≡CCu can be drawn as (t-BuC≡CCu)20 and (PhC≡CCu) ,
2
respectively. Most 1-copper(I) alkynes (1) can be simply prepared and isolated as insoluble crystalline
solids with extremely chemical stability. Therefore, their structures are poorly understood and their
reactions in organic synthesis are shortly studied to date. As shown in Scheme 1, their most important
application was in Castro-Stephens reaction, where the Cu(I)-C bond was substituted by various
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
3
electrophiles (a). Recently, a new application of them was reported by Evano, in which the Cu(I)-C
4
bond was substituted by nucleophiles through an oxidative cross-coupling mechanism (b). Herein, we
report that 1-copper(I) alkynes (1) can also carry out a novel tandem reaction with azides (2)
(cycloaddition) and then NCS (electrophilic substitution), where the reactivity of Cu(I)-C bond was not
involved in the first step to give 1,4,5-trisubstituted 5-chloro-1,2,3-triazoles (3) as the final products (c).
Scheme 1
additive as base or ligand
a. RC C Cu + E+
RC C
E
Castro-Stephens reaction
1
additive as base or ligand
b. RC C Cu + Nu-
RC C Nu
oxidative cross-coupling
1
N
R1
additive-free, one-pot N
N
1
c. RC C Cu + R N + NCS
3
this work
+
[
Cl ]
R
3
Cl
1
2
Recently, 1,4,5-trisubstituted 1,2,3-triazoles were reported to have important applications in organic
5–9
synthesis, biology and material sciences.
Prominent among them are 1,4,5-trisubstituted
6
–9
5-halo-1,2,3-triazoles (3-5) because they can be used as both product and precursor (Figure 1).
However, they can not be prepared by the normal CuAAC reaction (copper-catalyzed azide-alkyne
cycloaddition) in which only terminal alkynes are used as substrates and 1,4-disubstituted 1,2,3-triazoles
1
a,10
are produced.
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Arylation7
Alkynylation8
Page 4 of 16
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
N
R1
Intramolecular
Cyclization6
Nucleophilic
Substitution9
N
N
R
X
3
, X = Cl; 4, X = Br; 5, X = I
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
Figure 1. The synthetic applications of 1,4,5-trisubstituted 5-halo-1,2,3-triazoles
Many efforts have been made to develop the methods for the synthesis of 1,4,5-trisubstituted
5
-halo-1,2,3-triazoles (3-5). As shown in Scheme 2, an early method was to simply add an electrophile
+
X (X = Cl, Br and I) into a normal CuAAC reaction, by which the intermediate 5-copper(I)
8
a,8c,11
+
1,2,3-triazole (6)
was trapped in situ by X . Unfortunately, this method usually gave a mixture
containing both the desired product and the byproduct 1,4-disubstituted 1,2,3-triazole (7) due to a
+
competitive protonation of H . In some cases, the byproduct 7 was even the major product depending
+
upon the structure of the substrate. This drawback was unavoidable because this H came from the
terminal alkyne, which was the required substrate for a normal CuAAC reaction.
Scheme 2
Cu(I), Ln
R C C H
R C C CuLn
1, as a complex with ligands
H+
1
R N (2)
3
X+
R1
N
R1
N
R1
N
N
N
N
N
N
N
R
H
R
[Cu]
R
X
7
6
3-5
To overcome the drawbacks caused by terminal alkynes, 1-bromo-alkynes (8) were wisely
9b
introduced as the substrates (Figure 2). Under the modified CuAAC conditions, 1,4,5-trisubstituted
5
-bromo-1,2,3-triazoles (4) were produced smoothly by the cycloaddition of 8 and 2. Later,
1-iodo-alkynes (9) were proved to be the most suitable substrates for the synthesis of 1,4,5-trisubstituted
6,7b,12
5
-iodo-1,2,3-triazoles (5).
Recently, 1-alumino-alkynes (10) were reported to be versatile substrates
ACS Paragon Plus Environment

Page 5 of 16
The Journal of Organic Chemistry
1
3
for the synthesis of various 1,4,5-trisubstituted 1,2,3-triazoles including the products 3-5. But, there
are two drawbacks to this otherwise efficient method caused by the highly active Al-C bonds in both 10
and its reaction intermediates 5-alumino-1,2,3-triazoles (11). First, this method has to be performed
under anhydrous conditions because Al-C bonds are sensitive to moisture. Second, the method has to be
proceeded in two steps because these two Al-C bonds do not have chemoselectivity to the electrophile
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
+
X .
N
R1
RC C X
RC C AlMe2
N
N
8
9
, X = Br
, X = I
R
AlMe2
10
11
Figure 2. The structures of 8-11.
In our recent CuAAC project, 1-copper(I) alkynes (1) were used often as substrates and
14
intermediates in the synthesis of 1,4-disubstituted 1,2,3-triazoles. Interestingly, we found that they
were perfectly stable to air and moisture, but were still never used for the synthesis of
1
,4,5-trisubstituted 5-halo-1,2,3-triazoles (3-5). Thus, we were encouraged to develop an easy method
for the synthesis of 3-5 by using 1-copper(I) alkynes (1) as substrates. Unfortunately, the primary
experimental results indicated that only a complicated mixture was produced when the solution of
1
-copper(I) phenylethyne (1a) and benzyl azide (2a) in CH
2
Cl
2
was treated by NXS (X = Cl, Br or I) in
the presence of an additive (as base or ligand), such as Et
3
N, DIPEA, pyridine or 1,10-phenanthroline.
However, the same reactions gave a group of interesting results under the additive-free conditions. As
shown in Scheme 3, 1-iodo-phenylethyne was obtained in 98% yield as a single product after 1a, 2a and
2 2
NIS were mixed together in CH Cl for 10 minutes. By replacement of NIS with NBS, the same
reaction offered a mixture of 3a (2%), 1-bromo-phenylethyne (22%) and 1,4-diphenylbutadiyne (73%).
To our delight, the desired 3a was obtained in 88% yield as a major product when NCS served as an
electrophile.
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 6 of 16
Scheme 3
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
CH Cl , rt, additive-free
2
2
(
PhC CCu)
+
BnN3 + NXS
10 min for NIS
2 h for NBS
1a
2a
5
h for NCS
N
Bn
N
N
+
PhC C X
+
PhC C C CPh
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
Ph
X
5
4
3
a, X = I, 0%
a, X = Br, 2%
X = I, 98%
X = Br, 22%
X = Cl, 3%
0%
73%
3%
a, X = Cl, 88%
The results in Scheme 3 clearly indicate that the reaction products strongly depend upon the
properties of NXS. For example, NIS is a strong electrophile and therefore it undergoes a fast
electrophilic substitution with 1a to yield 1-iodo-phenylethyne as a unique product. However, NBS as a
moderate electrophile reacts slowly with 1a to initially yield some of 1-bromo-phenylethyne. Then, the
produced 1-bromo-phenylethyne further reacts with unreacted 1a to form 1,4-diphenylbutadiyne as a
major product by Castro-Stephens reaction. But, the conditional experiments showed that the
electrophilic substitution between 1a and NCS underwent very slowly under the same conditions (<
10% of 1a was consumed in 5 h) because NCS was the weakest electrophile compared to NIS and NBS.
Thus, a CuAAC reaction between 1a and 2a occurs preferentially to give 6a as an intermediate due to
1
5
the “click reaction” having a high thermodynamic driving force (Scheme 4). Then, the intermediate 6a
is trapped by NCS to give 3a. This result indicates that the Cu(I)-C bond of 1a has much lower
reactivity than that of 6a because 1a is a polymeric complex. This result also offers a rare example
whereby a tandem reaction of an organometallic substrate does not involve in the reactivity of the
metal-carbon bond in the first step.
Scheme 4
N
N
Bn
Bn
BnN (2a)
N
N
NCS
Cu(I)
N
N
3
(
PhC CCu)
Ph
[Cu]
Ph
Cl
1
a
6a
3a
ACS Paragon Plus Environment

Page 7 of 16
The Journal of Organic Chemistry
To further confirm the hypothesized pathway in Scheme 4, the cycloaddition of
1
2
1
-chloro-phenylethyne (PhC≡C-Cl) and 2a was tested in the presence of one equivalent of CuCl
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
(CH Cl , rt, 5 h). As was expected, no any desired product 3a was obtained and PhC≡C-Cl was
2
2
confirmed to be not an intermediate in the conversion of 1a to 3a. Thus far, we discovered a novel
tandem reaction method for the synthesis of 1,4,5-trisubstituted 5-chloro-1,2,3-triazoles (3). Since the
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
synthesis of 3 was the most difficult task among the isomers 3-5 and there were only three
9a,13,16
chemoselective procedures (a-c, Scheme 5)
for this purpose in literature to date, therefore this
mild and convenient tandem reaction method may be a valuable addition.
Scheme 5
1
2
. CuI (10 mol%), PMDTA
(10 mol%), PhMe, rt, 48 h
. NCS, THF, rt, 4 h
AlMe2
a.13
1
+ R N
3
1
R = Ph, R = Bn, 74%
R
KCl (5 equiv), aq. MeCN
N
R1
N
R1
o
N
N
N
N
MW, 180 C, 10 min
b.9a
1
R = Ph, R = Bn, 77%
R
I
R
Cl
3
CuCl (1 equiv), PivOH
N
R1
o
c.16
N
N
140 C, 46 h
1
R = Ph, R = n-hexyl, 74%
R
H
Since the product 3a was produced under extremely simple conditions, only the solvent needs to be
optimized. As shown in Table 1, the solvents have a significant effect on the yield of 3a and MeOH
gave the lowest yield (entry 1). Interestingly, halo-containing solvents, such as CHCl
3 2 2
, ClCH CH Cl
and CH Cl (entries 5-7), were all good solvents and CH Cl gave the best results (entry 7). The reaction
2
2
2
2
concentrations did not have comparable effect on the reaction (entries 7-9). Finally, the entry 7 was
assigned as our standard conditions.
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 8 of 16
a
Table 1. The effect of solvent on the reaction
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
Entry
Solvent
Concentration of 1a
Yield of 3a
b
(
mmol/mL)
(%)
1
2
3
4
5
6
7
8
9
MeOH
MeCN
Toluene
THF
0.5/1
0.5/1
0.5/1
0.5/1
0.5/1
0.5/1
0.5/1
0.5/2
32
53
57
70
76
84
88
83
85
CHCl
ClCH CH
CH Cl
CH Cl2
3
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
2
2
Cl
2
2
2
CH
2
Cl
2
0.5/4
a
The mixture of 1a (0.5 mmol), 2a (0.6 mmol) and NCS (0.6 mmol)
in solvent was stirred in a stoppered tube at room temperature for 5
b
h. The isolated yields.
As shown in Scheme 6, this novel method was general and efficient for the molecular diversity.
Under the standard conditions, 1-copper(I) alkynes (1), azides (2) and NCS reacted smoothly to give the
Scheme 6
N
R1
CH Cl , rt, 5 h N
N
1
2
2
(RC CCu) + R N + NCS
3
6
3-93%
R
Cl
1
2
3
N
N
N
N
N
N
N
N
N
N
N
N
Ph
Ph
Ph-4-Me
Ph-4-NO2
Nath-2
Ph
Cl
Ph
Cl
Ph
Cl
Ph
Cl
3
a, 88%
3b, 93%
3c, 86%
3d, 89%
N
N
N
N
Pri
N
N
N
N
N
N
N
N
6
Ph
Cl
Ph
Cl
Ph
Cl
Ph
Cl
3
e, 67%
3f, 83%
3g, 81%
3h, 63%
N
N
N
N
N
N
OMe
N
N
N
N
N
N
Ph
Ph
Ph
Ph
OMe
Ph
Cl
4-MePh
Cl
4-MeOPh
Cl
4-NO Ph
Cl
2
3
i, 82%
3j, 91%
3k, 80%
3l, 85%
N
N
N
N
N
N
N
N
N
N
N
N
Ph
Ph
Ph
2
-FPh
Cl
3-FPh
Cl
4-ClPh
Cl
Cl
3p, 83%
3
m, 85%
3n, 89%
3o, 82%
N
N
N
N
N
N
N
N
N
N
N
N
Ph-4-NO2
Ph-4-Me
Ph-4-Me
Ph-4-Me
4-ClPh
Cl
4-MePh
Cl
4-ClPh
Cl
3-FPh
Cl
3q, 92%
3r, 87%
3s, 80%
3t, 82%
ACS Paragon Plus Environment

Page 9 of 16
The Journal of Organic Chemistry
corresponding 1,4,5-trisubstituted 5-chloro-1,2,3-trizoles (3a-3t) in satisfactory yields. By fixing
-copper(I) phenylethyne (1a), all tested azides were suitable substrates (see: the products 3a-3i) and the
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
1
azides bearing bulky groups gave relatively low yields (see: the products 3e and 3h). By fixing benzyl
azide (2a), no apparent difference was observed for all tested 1-copper(I) alkynes, no matter which
electron-donating-groups (see: the products 3j-3k) or electron-withdrawing-groups (see: the product 3l)
are on the arylethynes.
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
In conclusion, a novel tandem reaction method was established for the preparation of
1
,4,5-trisubstituted 5-chloro-1,2,3-triazoles by directly using the isolated 1-copper(I) alkynes as
substrates. The method shows noteworthy importance because it proceeds under mild conditions and its
products are expected to have important medicinal properties.
Experimental Section
1
13
The H NMR (300 MHz) and C NMR (75 MHz) spectra were recorded in CDCl . TMS was used
3
as an internal reference and J values are given in Hz. 1-Copper(I) alkynes (1) were prepared according
3c
to the procedure reported in reference.
A Typical Procedure for the Preparation of 1-Benzyl-4-phenyl-5-chloro-1,2,3-triazole (3a). To
a suspension of 1-copper(I) phenylethyne (1a, 82 mg, 0.5 mmol) and benzyl azide (2a, 80 mg, 0.6
2 2
mmol) in CH Cl (1 mL) was added NCS (80 mg, 0.6 mmol). The resultant mixture was stirred at room
temperature for 5 h and then passed through a column chromatography [silica gel, 10% EtOAc in
o
o
13
petroleum ether (60–90 C)] to give 119 mg (88%) of product 3a as a white solid, mp 60–62 C (lit.
-1 1
mp 58–60 °C). IR (KBr) v 3063, 3035, 2952, 1606 cm ; H NMR 7.97–7.91 (m, 2H), 7.45–7.26 (m,
1
3
8
H), 5.52 (s, 2H); C NMR 141.8, 133.7, 129.2, 128.8 (2C), 128.6 (2C), 128.5, 128.4, 127.7 (2C),
+
126.2 (2C), 121.6, 51.9; HRMS (ESI-TOF) (m/z): calcd for C15
70.0792.
H12ClN
3
, [M + H] 270.0793; found
2
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 10 of 16
The similar procedure was used for the preparation of products 3b-3t.
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
1
-(4-Methylbenzyl)-4-phenyl-5-chloro-1,2,3-triazole (3b). White solid, 132 mg (93%), mp 83–85
o
-1
1
C; IR (KBr) v 3028, 2984, 1611 cm ; H NMR  7.96 (d, J = 7. 92 Hz, 2H), 7.44–7.31 (m, 3H),
13
7
.21–7.12 (m, 4H), 5.49 (s, 2H), 2.30 (s, 3H); C NMR  141.8, 138.4, 130.8, 129.5 (2C), 129.2, 128.5
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
(
3
2C), 128.4, 127.7 (2C), 126.2 (2C), 121.5, 51.8, 21.0; HRMS (ESI-TOF) (m/z): calcd for C16H14ClN ,
+
[M + H] 284.0949; found 284.0950.
1-(4-Nitrobenzyl)-4-phenyl-5-chloro-1,2,3-triazole (3c). White solid, 135 mg (86%), mp 123–125
o
-1
1
C; IR (KBr) v 3079, 2953, 2851, 1606 cm ; H NMR  8.24–8.14 (m, 2H), 7.99–7.90 (m, 2H),
1
3
7.52–7.33 (m, 5H), 5.67 (s, 2H); C NMR  147.9, 142.1, 140.6, 128.8, 128.7 (3C), 128.5 (2C), 126.1
+
(
2C), 124.1 (2C), 121.7, 50.9; HRMS (ESI-TOF) (m/z): calcd for C15
found 315.0642.
-(2-Naphthylmethyl)-4-phenyl-5-chloro-1,2,3-triazole (3d). White solid, 142 mg (89%), mp
H11ClN
4
O
2
, [M + H] 315.0643;
1
o
-1 1
95–97 C; IR (KBr) v 3055, 1601 cm ; H NMR  7.98–7.96 (m, 2H), 7.82–7.74 (m, 4H), 7.50–7.32 (m,
13
6
H), 5.69 (s, 2H); C NMR  142.0, 133.0 (2C), 131.1, 129.2, 128.9, 128.6 (2C), 128.5, 127.9, 127.7,
127.0, 126.5 (2C), 126.2 (2C), 125.0, 121.7, 52.2; HRMS (ESI-TOF) (m/z): calcd for C19
H
14ClN
3
, [M +
+
H] 320.0949; found 320.0951.
o
1
-(1-Ethylbenzyl)-4-phenyl-5-chloro-1,2,3-triazole (3e). White solid, 95 mg (67%), mp 88–90 C;
-1 1
IR (KBr) v 3063, 3032, 2990, 1607 cm ; H NMR  7.98–7.95 (m, 2H), 7.47–7.24 (m, 8H), 5.71 (q, J =
1
3
6
.87 Hz, 1H), 2.07 (d, J = 6.87 Hz, 3H); C NMR  141.8, 139.5, 129.3, 128.8 (2C), 128.5 (2C), 128.3,
+
1
28.2, 126.3 (4C), 121.4, 58.9, 21.3; HRMS (ESI-TOF) (m/z): calcd for C H ClN , [M + H]
1
6
14
3
284.0949; found 284.0948.
1-Octyl-4-phenyl-5-chloro-1,2,3-triazole (3f). Yellow oil, 121 mg (83%); IR (KBr) v 3062, 3033,
-1 1
2
956, 2855, 1608 cm ; H NMR  8.00–7.96 (m, 2H), 7.48–7.26 (m, 3H), 4.35 (t, J = 7.20 Hz, 2H),
ACS Paragon Plus Environment

Page 11 of 16
The Journal of Organic Chemistry
1
3
1
.98–1.91 (m, 2H), 1.34–1.27 (m, 10H), 0.88 (t, J = 7. 20 Hz, 3H); C NMR  141.5, 129.4, 128.6 (2C),
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
128.3, 126.2 (2C), 121.3, 48.4, 31.6, 29.3, 29.0, 28.9, 26.3, 22.5, 14.0; HRMS (ESI-TOF) (m/z): calcd
+
for C16
H22ClN
3
, [M + H] 292.1575; found 292.1577.
1
-(3-Methylbutyl)-4-phenyl-5-chloro-1,2,3-triazole (3g). Yellow oil, 101 mg (81%); IR (KBr) v
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
-1 1
3
062, 2958, 2871, 1608 cm ; H NMR  7.99–7.96 (m, 2H), 7.48–7.33 (m, 3H), 4.36 (t, J = 7.56 Hz,
1
3
2H), 1.86–1.78 (m, 2H), 1.70–1.61 (m, 1H), 0.99 (d, J = 6.51Hz, 6H); C NMR  141.5, 129.3, 128.5
(
2C), 128.3, 126.2 (2C), 121.2, 46.7, 37.9, 25.4, 22.1 (2C); HRMS (ESI-TOF) (m/z): calcd for
+
C H ClN , [M + H] 250.1106; found 250.1107.
1
3
16
3
o
1
-Cyclohexyl-4-phenyl-5-chloro-1,2,3-triazole (3h). Green solid, 82 mg (63%), mp 100–102 C;
-1 1
IR (KBr) v 3074, 2931, 2855, 1611 cm ; H NMR  7.99–7.93 (m, 2H), 7.48–7.34 (m, 3H), 4.41–4.31
1
3
(
(
m, 1H), 2.14–1.95 (m, 6H), 1.79–1.74 (m, 1H), 1.51–1.26 (m, 3H); C NMR  141.4, 129.6, 128.6
2C), 128.3, 126.4 (2C), 120.6, 58.6, 32.3 (2C), 25.3 (2C), 25.0; HRMS (ESI-TOF) (m/z): calcd for
+
C
14
H16ClN
3
, [M + H] 262.1106; found 262.1104.
1
-(2,2-Dimethoxylethyl)-4-phenyl-5-chloro-1,2,3-triazole (3i). Colorless oil, 110 mg (82%); IR
-1 1
(KBr) v 3061, 3029, 2959, 2836, 1608 cm ; H NMR  8.00–7.97 (m, 2H), 7.48–7.27 (m, 3H), 4.87 (t, J
13
=
5.52 Hz, 1H), 4.46 (d, J = 5.52 Hz, 2H), 3.40 (s, 6H); C NMR  141.3, 129.2, 128.5 (2C), 128.3,
+
1
26.2 (2C), 122.3, 101.8, 54.5 (2C), 49.2; HRMS (ESI-TOF) (m/z): calcd for C12
68.0847; found 268.0848.
1-Benzyl-4-(4-methylphenyl)-5-chloro-1,2,3-triazole (3j). White solid, 129 mg (91%), mp 76–78
3 2
H14ClN O , [M + H]
2
o
-1 1
C; IR (KBr) v 3065, 2951, 2871, 1645 cm ; H NMR  7.84 (d, J = 8.25 Hz, 2H), 7.34–7.18 (m, 7H),
1
3
5.49 (s, 2H), 2.34 (s, 3H); C NMR  141.9, 138.2, 133.8, 129.2 (2C), 128.8 (2C), 128.4, 127.6 (2C),
+
1
26.3, 126.0 (2C), 121.1, 51.8, 21.1; HRMS (ESI-TOF) (m/z): calcd for C H ClN , [M + H]
16 14 3
284.0949; found 284.0947.
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 12 of 16
1
-Benzyl-4-(4-methoxyphenyl)-5-chloro-1,2,3-triazole (3k). White solid, 120 mg (80%), mp
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
o
-1 1
6
5
1
1–62 C. IR (KBr) v 3063, 3033, 2940, 2836, 1612 cm ; H NMR  7.91–7.87 (m, 2H), 7.37–7.24 (m,
13
H), 6.99–6.94 (m, 2H), 5.52 (s, 2H), 3.81 (s, 3H); C NMR  159.7, 141.8, 133.8, 128.8 (2C), 128.5,
27.7 (2C), 127.5 (2C), 121.8, 120.7, 114.0 (2C), 55.2, 51.9; HRMS (ESI-TOF) (m/z): calcd for
+
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
C
16
H14ClN
3
O, [M + H] 300.0898; found 300.0901.
1-Benzyl-4-(4-nitrophenyl)-5-chloro-1,2,3-triazole (3l). Yellow solid, 134 mg (85%); mp
o
-1 1
1
30–132 C. IR (KBr) v 3033, 1599 cm ; H NMR  8.30 (d, J = 8.25 Hz, 2H), 8.18 (d, J = 8.25 Hz,
1
3
2H), 7.40–7.32 (m, 5H), 5.61 (s, 2H); C NMR  147.4, 139.9, 135.5, 133.3, 129.1 (2C), 128.8, 127.9
+
(
2C), 126.6 (2C), 124.0 (2C), 123.2, 52.3; HRMS (ESI-TOF) (m/z): calcd for C H ClN O , [M + H]
15 11 4 2
3
15.0643; found 315.0644.
-Benzyl-4-(2-flourophenyl)-5-chloro-1,2,3-triazole (3m). Colorless oil, 122 mg (85%); IR (KBr)
1
-1 1
v 3066, 3034, 2951, 2855, 1582 cm ; H NMR  7.70–7.64 (m, 1H), 7.41–7.28 (m, 6H), 7.24–7.12 (m,
1
3
2
H), 5.56 (s, 2H); C NMR  159.5 (d, J = 249.0 Hz), 138.7, 133.7, 130.7 (d, J = 2.9 Hz, 2C), 128.9
(2C), 128.5, 127.8 (2C), 124.2 (d, J = 2.8 Hz), 124.0, 117.1 (d, J = 14.3 Hz), 115.9 (d, J = 21.5 Hz),
+
5
2.1; HRMS (ESI-TOF) (m/z): calcd for C15
H
11ClFN
3
, [M + H] 288.0698; found 288.0700.
1
-Benzyl-4-(3-flourophenyl)-5-chloro-1,2,3-triazole (3n). White solid, 128 mg (89%), mp 64–66
o
-1
1
C; IR (KBr) v 3079, 3035, 2925, 1617 cm ; H NMR  7.77–7.67 (m, 2H), 7.43–7.24 (m, 6H),
1
3
7
.08–7.01 (m, 1H), 5.56 (s, 2H); C NMR  162.8 (d, J = 243.8 Hz), 140.8, 133.6, 131.3 (d, J = 8.6 Hz),
1
30.3 (d, J = 7.9 Hz), 128.9 (2C), 128.6, 127.8 (2C), 122.0, 121.7, 115.3 (d, J = 20.8 Hz), 113.1 (d, J =
+
23.0 Hz), 52.1; HRMS (ESI-TOF) (m/z): calcd for C H ClFN , [M + H] 288.0698; found 288.0701.
1
5
11
3
1-Benzyl-4-(4-chlorophenyl)-5-chloro-1,2,3-triazole (3o). White solid, 125 mg (82%), mp
o
-1 1
1
24–126 C; IR (KBr) v 3066, 3034, 2933, 1603 cm ; H NMR  7.92–7.89 (m, 2H), 7.42–7.31 (m, 7H),
1
3
5.56 (s, 2H); C NMR  141.0, 134.4, 133.6, 129.0 (2C), 128.9 (2C), 128.7, 127.8 (3C), 127.5 (2C),
+
1
21.7, 52.1; HRMS (ESI-TOF) (m/z): calcd for C15
H11Cl
2
N
3
, [M + H] 304.0403; found 304.0402.
ACS Paragon Plus Environment

Page 13 of 16
The Journal of Organic Chemistry
1
-Benzyl-4-isopropenyl-5-chloro-1,2,3-triazole (3p). Colorless oil, 97 mg (83%); IR (KBr) v 3065,
1
2
-1 1
3
034, 2980, 2953, 1635 cm ; H NMR  7.37–7.26 (m, 5H), 5.70 (s, 1H), 5.49 (s, 2H), 5.24(s, 1H), 2.23
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
13
(
(
s, 3H); C NMR  142.6, 133.8, 133.3, 128.8 (2C), 128.4, 127.7 (2C), 121.5, 114.5, 51.8, 21.1; HRMS
+
ESI-TOF) (m/z): calcd for C12
H12ClN
3
, [M + H] 234.0793; found 234.0795.
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
-(4-Nitrobenzyl)-4-(4-chlorophenyl)-5-chloro-1,2,3-triazole (3q). Yellow solid, 161 mg (92%),
o
-1 1
mp 134–136 C; IR (KBr) v 2925, 2852, 1603 cm ; H NMR  8.23 (d, J = 8.94 Hz, 2H), 7.96–7.88 (m,
1
3
2
H), 7.53–7.40 (m, 4H), 5.68 (s, 2H); C NMR  148.0, 141.2, 140.4, 134.6, 128.9 (2C), 128.6 (2C),
+
127.4 (2C), 127.3, 124.2 (2C), 121.8, 51.1; HRMS (ESI-TOF) (m/z): calcd for C15
49.0254; found 349.0253.
-(4-Methylbenzyl)-4-(4-methylphenyl)-5-chloro-1,2,3-triazole (3r). White solid, 130 mg (87%),
2 4 2
H10Cl N O , [M + H]
3
1
o
-1 1
mp 52–54 C; IR (KBr) v 3023, 2920, 2856, 1649 cm ; H NMR  7.84 (d, J = 8.25 Hz, 2H), 7.24–7.08
1
3
(
m, 6H), 5.47 (s, 2H), 2.35 (s, 3H), 2.30 (s, 3H); C NMR  141.9, 138.3, 138.2, 130.8, 129.5 (2C),
1
29.2 (2C), 127.7 (2C), 126.4, 126.1 (2C), 121.1, 51.7, 21.2, 21.0; HRMS (ESI-TOF) (m/z): calcd for
+
C
17
H
16ClN
3
, [M + H] 298.1106; found 298.1107.
1-(4-Methylbenzyl)-4-(4-chlorophenyl)-5-chloro-1,2,3-triazole (3s). White solid, 127 mg (80%),
o
-1 1
mp 83–85 C; IR (KBr) v 3025, 2920, 1608 cm ; H NMR  7.93–7.87 (m, 2H), 7.42–7.37 (m, 2H),
13
7.23–7.13 (m, 4H), 5.50 (s, 2H), 2.32 (s, 3H); C NMR  140.9, 138.5, 134.3, 130.6, 129.6 (2C), 128.8
(
2 3
2C), 127.8 (2C), 127.4 (2C), 124.9, 121.6, 51.9, 21.1; HRMS (ESI-TOF) (m/z): calcd for C16H13Cl N ,
+
[
M + H] 318.0559; found 318.0561.
1
-(4-Methylbenzyl)-4-(3-fluorophenyl)-5-chloro-1,2,3-triazole (3t). White solid, 124 mg (82%),
o
-1 1
mp 98–100 C; IR (KBr) v 3026, 2956, 2855, 1617 cm ; H NMR  7.77–7.67 (m, 2H), 7.43–7.36 (m,
13
1
H), 7.25–7.14 (m, 4H), 7.08–7.02 (m, 1H), 5.52 (s, 2H), 2.33 (s, 3H); C NMR  162.9 (d, J = 243.8
Hz), 140.8, 138.6, 131.4 (d, J = 8.6 Hz), 130.6, 130.3 (d, J = 8.6 Hz), 129.6 (2C), 127.8 (2C), 121.9,
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 14 of 16
1
21.8, 115.3 (d, J = 21.5 Hz), 113.1 (d, J = 23.7 Hz), 52.0, 21.1; HRMS (ESI-TOF) (m/z): calcd for
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
+
C H ClFN , [M + H] 302.0855; found 302.0856.
16 13
3
Acknowledgements. This work was supported by the National Natural Scientific Foundation of
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
China (21072112 and 21221062).
1
13
Supporting Information Available. H and C NMR spectra for products 3a-3t. This material is
available free of charge via the Internet at http://pubs.acs.org.
References
(
(
1) For selected reviews, see: (a) Meldal, M.; Tornøe, C. W. Chem. Rev. 2008, 108, 2952–3015 [see: pp
2954–2955 for the structure discussions]. (b) Lang, H.; Kohler, K.; Blau, S. Coord. Chem. Rev.
1
995, 143, 113–168. (c) Nast, R. Coord. Chem. Rev. 1982, 47, 89–124.
2) Chui, S. S. Y.; Ng, M. F. Y.; Che, C.-M. Chem.-Eur. J. 2005, 11, 1739–1749.
(3) (a) Kraus, M. J. Taschner, G. A. J. Am. Chem. Soc. 1980, 102, 1974–1977. (b) Batu, G.; Stevenson,
R. J. Org. Chem. 1980, 45, 1532–1534. (c) Owsley, D. C.; Castro, C. E. Org. Synth. 1972, 52,
1
28–131. (d) Normant, J. F.; Bourgain, M. Tetrahedron Lett. 1970, 2659–2662. (e) Castro, C. E.;
Havlin, R.; Honwad, V. K.; Malte, A.; Moje, S. J. Am. Chem. Soc. 1969, 91, 6464–6470. (f)
Stephens, R. D.; Castro, C. E. J. Org. Chem. 1963, 28, 3313–3315.
(4) Jouvin, K.; Heimburger, J.; Evano, G. Chem. Sci. 2012, 3, 756–760.
(
5) For selected references, see: (a) Chaubard, J.–L.; Krishnamurthy, C.; Yi, W.; Smith, D. F.;
Hsieh-Wilson, L. C. J. Am. Chem. Soc. 2012, 134, 4489−4492. (b) Beal, D. M.; Albrow, V. E.;
Burslem, G.; Hitchen, L.; Fernandes, C.; Lapthorn, C.; Roberts, L. R.; Selby, M. D.; Jones, L. H.
Org. Biomol. Chem. 2012, 10, 548–554. (c) Durka, M.; Tikad, A.; Perion, R.; Bosco, M.;
ACS Paragon Plus Environment

Page 15 of 16
The Journal of Organic Chemistry
Andaloussi, M.; Floquet, S.; Malacain, E.; Moreau, F.; Oxoby, M.; Gerusz, V.; Vincent, S. P. Chem.
Eur. J. 2011, 17, 11305–11313. (d) Dommerholt, J.; Schmidt, S.; Temming, R.; Hendriks, L. J. A.;
Rutjes, F. P. J. T.; van Hest, J. C. M.; Lefeber, D. J.; Friedl, P.; van Delft, F. L. Angew. Chem., Int.
Ed. 2010, 49, 9422–9425. (e) Kilah, N. L.; Wise, M. D.; Serpell, C. J.; Thompson, A. L.; White, N.
G.; Christensen, K. E.; Beer, P. D. J. Am. Chem. Soc. 2010, 132, 11893–11895.
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(
(
6) (a) Schulman, J. M.; Friedman, A. A.; Panteleev, J.; Lautens, M. Chem. Commun. 2012, 48, 55–57.
(
b) Juricek, M.; Stout, K.; Kouwer, P. H. J.; Rowan, A. E. Org. Lett. 2011, 13, 3494–3497. (c)
Panteleev, J.; Geyer, K.; Aguilar-Aguilar, A.; Wang, L.; Lautens, M. Org. Lett. 2010, 12,
092–5095.
5
7) (a) Simone, R. D.; Chini, M. G.; Bruno, I.; Riccio, R.; Mueller, D.; Werz, O.; Bifulco, G. J. Med.
Chem. 2011, 54, 1565–1575. (b) Hein, J. E.; Tripp, J. C.; Krasnova, L. B.; Sharpless, K. B.; Fokin,
V. V. Angew. Chem., Int. Ed. 2009, 48, 8018–8021. (c) Diner, P.; Andersson, T.; Kjellen, J.; Elbing,
K.; Hohmann, S.; Groli, M. New J. Chem. 2009, 33, 1010–1016. (d) Deng, J.; Wu, Y.-M.; Chen,
Q.-Y. Synthesis 2005, 2730–2738.
(
8) (a) Morris, J. C.; Chiche, J.; Grellier, C.; Lopez, M.; Bornaghi, L. F.; Maresca, A.; Supuran, C. T.;
Pouyssegur, J.; Poulsen, S.-A. J. Med. Chem. 2011, 54, 6905–6918. (b) Ostrowski, T.; Januszczyk,
P.; Cieslak, M.; Kazmierczak- Baranska, J.; Nawrot, B.; Bartoszak-Adamska, E.; Zeidler, J. Bioorg.
Med. Chem. 2011, 19, 4386–4398. (c) Malnuit, V.; Duca, M.; Manout, A.; Bougrin, K.; Benhida, R.
Synlett 2009, 2123–2128. (d) Joubert, N.; Schinazib, R. F.; Agrofoglio, L. A. Tetrahedron 2005, 61,
1
1744–11750.
(
9) (a) Worrell, B. T.; Hein, J. E.; Fokin, V. V. Angew. Chem., Int. Ed. 2012, 51, 11791–11794. (b)
Kuijpers, B. H. M.; Dijkmans, G. C. T.; Groothuys, S.; Quaedflieg, P. J. L. M.; Blaauw, R. H.; van
Delft, F. L.; Rutjes, F. P. J. T. Synlett 2005, 3059–3062. (c) Buckle, D. R.; Outred, D. J.; Rockell, C.
J. M.; Smith, H.; Spicer, B. A. J. Med. Chem. 1983, 26, 251–254.
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 16 of 16
(
10) For selected reviews, see: (a) Hein, J. E.; Fokin, V. V. Chem. Soc. Rev. 2010, 39, 1302–1315. (b)
Bock, V. D.; Hiemstra, H.; van Maarseveen, J. H. Eur. J. Org. Chem. 2006, 51–68.
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
(11) (a) Barsoum, D. N.; Brassard, C. J.; Deeb, J. H. A.; Okashah, N.; Sreenath, K.; Simmons, J. T.; Zhu,
L. Synthesis 2013, 45, 2372−2386. (b) Li, L.; Li, R.; Zhu, A.; Zhang, G.; Zhang, L. Synlett 2011,
8
5
74–878. (c) Smith, N. W.; Polenz, B. P.; Johnson, S. B.; Dzyuba, S. V. Tetrahedron Lett. 2010, 51,
50–553. (d) Li, L.; Zhang, G. G.; Zhu, A.; Zhang, L. J. Org. Chem. 2008, 73, 3630–3633. (e) Wu,
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
Y.; Deng, J.; Li, Y.; Chen, Q.-Y. Synthesis 2005, 1314–1318.
(12) (a) Brotherton, W. S.; Clark, R. J.; Zhu, L. J. Org. Chem. 2012, 77, 6443−6455. (b) Garcia-Alvarez,
J.; Diez, J.; Gimeno, J. Green Chem. 2010, 12, 2127–2130.
(13) Zhou, Y.; Lecourt, T.; Micouin, L. Angew. Chem., Int. Ed. 2010, 49, 2607–2610.
(
14)(a) Zhang, Q.; Wang, X.; Cheng, C.; Zhu, R.; Liu, N.; Hu, Y. Org. Biomol. Chem. 2012, 10,
2847–2854. (b) Shao, C.; Wang, X.; Zhang, Q.; Luo, S.; Zhao, J.; Hu, Y. J. Org. Chem. 2011, 76,
6
6
832–6836. (c) Liu, Y.; Wang, X.; Xu, J.; Zhang, Q.; Zhao, Y.; Hu, Y. Tetrahedron 2011, 67,
294–6299. (d) Shao, C.; Zhu, R.; Luo, S.; Zhang, Q.; Wang, X.; Hu, Y. Tetrahedron Lett. 2011, 52,
3782–3785. (e) Shao, C.; Wang, X.; Xu, J.; Zhao, J.; Zhang, Q.; Hu, Y. J. Org. Chem. 2010, 75,
7
1
002–7005. (f) Shao, C.; Cheng, G.; Su, D.; Xu, J.; Wang, X.; Hu, Y. Adv. Synth. Catal. 2010, 352,
587–1592.
(
(
15) For selected references, see: (a) Rodionov, V. O.; Fokin, V. V.; Finn, M. G. Angew. Chem., Int. Ed.
005, 44, 2210–2215. (b) Himo, F.; Lovell, T.; Hilgraf, R.; Rostovtsev, V. V.; Noodleman, L.;
2
Sharpless, K. B.; Fokin, V. V. J. Am. Chem. Soc. 2005, 127, 210–216. (c) Kolb, H. C.; Finn, M. G.;
Sharpless, K. B. Angew. Chem., Int. Ed. 2001, 40, 2004–2021.
16) Menendez, C.; Saffon, N.; Lherbet, C.; Baltas, M. Synlett 2012, 23, 2623–2626.
ACS Paragon Plus Environment