CuI/Et 2 NH-Catalyzed One-Pot Highly Efficient Synthesis of 1,4-Disubstituted 1,2,3-Triazoles in Green Solvent Glycerol

Article abstract of DOI:10.1055/s-0036-1591557

A concise one-pot three-component reaction of organic halides, terminal acetylenes, and sodium azide provided an efficient route for the synthesis of 1,2,3-triazoles. A variety of 1,2,3-triazoles were prepared in good to excellent yields with green solven

Full text of DOI:10.1055/s-0036-1591557

SYNTHESIS
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© Georg Thieme Verlag Stuttgart · New York
2018, 50, A–I
paper
A
en
S. Guo et al.
Paper
Synthesis
CuI/Et2NH-Catalyzed One-Pot Highly Efficient Synthesis of
1,4-Disubstituted 1,2,3-Triazoles in Green Solvent Glycerol
Shengqiang Guoa
Yang Zhoub
Bencai Daib
Cuimeng Huob
Changchun Liub
Yongde Zhao*a,b
..............................
*Green solvent
R2
R1
NaN3
X
*Broad scope
N
N
N
R2
*Mild conditions
..............................
CuI (0.01 equiv)
Et2NH (0.05 equiv)
R1
22 examples
one pot
glycerol, r.t.
Yield 37–99%
a College of Chemistry and Chemical Engineering, Henan University,
Kaifeng, Henan 475004, P. R. China
ydzhao1549@sina.com
b Institute of Chemistry Co. Ltd., Henan Academy of Sciences,
Zhengzhou 450002, P. R. China
R1 = XC6H4 (X = 4-Et, 4-MeO, 3-MeO, 4-F, 2-F), pyridin-2-yl, pyridin-3-yl,
thiophen-2-yl, cyclohexan-1-ol, cyclopropyl, Et3Si, Ph
R
2 = XC6H4 (X = 4-Me, 3-Me, 3-CH3O, 4-O2N, 3-Cl, 4-F, penta-F, 3-CF3O),
cyclopropylmethyl, Bu, Ph
Received: 04.01.2018
Accepted after revision: 27.02.2018
Published online: 28.03.2018
From green chemistry perspective, one of the vital
points in realizing a ‘green chemical’ process involves the
use of a safe, non-toxic, and cheap solvent, especially in nu-
merous industrial processes.11 Indeed, water is the first sol-
vent of choice, yet the low solubility of most organic and or-
ganometallic compounds in water limits its applications.
Some researchers successfully synthesized 1,2,3-triazoles
using water as the solvent. However, the success of these
methods correlated closely with the assistance of micro-
wave,12 surfactants,13 or nanometer catalyst.14 All of these
treatments make the reaction much more complicated. Like
water, glycerol is also naturally available, highly hydrophil-
ic, environmentally friendly, and inexpensive. These advan-
tages make it an ideal candidate from the environmental
and economic standpoint.15 In recent years, chemists have
achieved many classical chemical reactions using glycerol
as the solvent.16 However, to the best of our knowledge,
there were no attempts to apply glycerol as solvent in the
synthesis of 1,2,3-triazoles so far.
In addition, the new methods for the synthesis of 1,2,3-
triazoles developed in recent years were largely due to the
preparation of novel catalysts and ligands, which were gen-
erally difficult to obtain because of their tricky synthetic
routes.17 A suitable catalytic system should not only make
the reaction more convenient but also make the reaction
easier to spread and apply in the practical applications.
Therefore, the development of an alternative concise, and
practical strategy method is still desirable and essential.
Reported here (Scheme 1) is a mild and experimentally
simple three-component catalytic reaction pathway for the
synthesis of 1,4-disubstituted 1,2,3-triazoles, which uses
glycerol as solvent and readily available CuI as catalyst. This
approach exhibits wide substrate scope and ambient reaction
condition and can be easily used for large-scale preparation.
DOI: 10.1055/s-0036-1591557; Art ID: ss-2018-h0700-op
Abstract A concise one-pot three-component reaction of organic
halides, terminal acetylenes, and sodium azide provided an efficient
route for the synthesis of 1,2,3-triazoles. A variety of 1,2,3-triazoles
were prepared in good to excellent yields with green solvent glycerol.
This procedure used CuI and diethylamine, which are two easily avail-
able reagents as the new catalytic system at room temperature.
Keywords green solvent, glycerol, copper(I) iodide, diethylamine, tri-
azoles, one-pot synthesis
In the past decades, 1,2,3-triazole derivatives were
unique nitrogen-containing heterocyclic scaffolds and at-
tracted much attention1 as they have been widely used in
the fields of biochemical science,2 material chemistry,3 me-
dicinal chemistry,4 and synthetic organic chemistry.5,1d
Therefore, the development of new, rapid, and efficient pro-
tocols for the synthesis of 1,2,3-triazoles has drawn exten-
sive attention. Several methods have been developed for the
preparation of these compounds;6 without controversy, Cu-
catalyzed click chemistry of organic azide with terminal
alkyne is the most efficient method.7,1d This click reaction
has many remarkable advantages, including good function-
ality tolerance, mild reaction conditions, exclusive regiose-
lectivity, operational simplicity, and high yields. Organic
azides are currently safe compounds, but those of low mo-
lecular weight can be environmentally sensitive, hence, dif-
ficult to handle.8 A number of methodologies were devel-
oped by using a three-component reaction of organic ha-
lides, terminal acetylenes, and sodium azide in order to
avert the isolation of organic azides.9 Unfortunately, most of
these methods for synthesizing 1,2,3-triazoles could not
avoid the use of expensive and toxic organic solvents such
as DMF, THF, and DMSO.10
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B
S. Guo et al.
Paper
Synthesis
temperature (Table 1, entries 1–4). To our delight, using
copper catalyst independently could reach a fairly high
yield and the catalytic effect of CuI was the best (89%). The
N
CuI, glycerol
N
N
R2
R2
R1
NaN3
X
Et2NH
R1
1
structure of product 4 was analyzed by H NMR, 13C NMR
R1 = XC6H4 (X = 4-Et, 4-MeO, 3-MeO, 4-F, 2-F), pyridin-2-yl, pyridin-3-yl,
thiophen-2-yl, cyclohexan-1-ol, cyclopropyl, Et3Si, Ph
and mass spectrometry and compared with the reported
characterization data. Further research showed that cata-
lytic quantity of nitrogen-containing ligands had an effec-
tive influence on the catalytic efficiency of CuI. Specifically,
diethylamine raised the yield and shortened the reaction
time; the highest yield was 98% (entries 5–10). Control ex-
periments suggested that CuI was essential for this trans-
formation (entries 11, 12). At last, to find the most suitable
solvent for this catalytic system, other solvents such as
EtOH, acetic ether and THF were used (entries 13–20). The
results showed that glycerol had the best reaction efficien-
cy in our experiments. Eventually, we determined the final
reaction conditions that used catalyst CuI and ligand di-
ethylamine in solvent glycerol at room temperature.
R2 = XC6H4 (X = 4-Me, 3-Me, 3-CH3O, 4-O2N, 3-Cl, 4-F, penta-F, 3-CF3O),
cyclopropylmethyl, Bu, Ph
Scheme 1 Our strategy for the construction of 1,4-disubstituted
1,2,3-triazoles
Taking into account this promising green solvent glycer-
ol, a systematic screening of catalyst systems was carried
out. Phenylacetylene (1a), sodium azide (2a), and benzyl
bromide (3a) were selected as model reaction to optimize
the conditions (Table 1). First, we purposely screened inex-
pensive and commercially available copper catalysts, in-
cluding CuBr, CuSO4 + sodium ascorbate, CuI, etc. at room
Table 1 Optimization of Reaction Conditionsa
N
cat., ligand
solvent
Bn
N
N
NaN3
Ph
Bn Br
3a
1a
2a
4a
Ph
Entry
Catalyst
CuSO4
Ligand
Solvent
Yield (%)b
Time (h)
1
2
–
–
–
–
glycerol
glycerol
glycerol
glycerol
glycerol
glycerol
glycerol
glycerol
glycerol
glycerol
glycerol
glycerol
EtOH
74
69
74
89
19
82
84
86
98
18
–
7
8
CuSO4 + sodium ascorbate
3
CuSO4 + Cu
CuI
CuI
CuI
CuI
CuI
CuI
CuI
–
8
4
7
5
ethylenediamine
Et3N
24
6
6
7
pyridine
DMAP
6
8
6
9
Et2NH
3
10
11
12
13
14
15
16
17
18
19
20
propane-1,3-diamine
–
24
–
–
Et2NH
–
–
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
Et2NH
80
–
10
–
Et2NH
acetic ether
CH2Cl2
THF
Et2NH
79
23
69
68
73
69
12
24
12
10
10
10
Et2NH
Et2NH
MeCN
acetone
H2O
Et2NH
Et2NH
Et2NH
–
a Reaction conditions: 1a (0.24 mmol), 2a (0.24 mmol), 3a (0.20 mmol), and cat. (0.002 mmol), ligand (0.01 mmol), solvent (1 mL). All reactions were carried
out under N2 atmosphere and monitored by HPLC until completion of the reaction.
b Isolated yield.
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S. Guo et al.
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Synthesis
With the optimized reaction conditions in hand, the
substrate scope was investigated next. The substituents of
aromatic alkynes were first evaluated as shown in Scheme
2, most of them performed smoothly and the correspond-
ing triazoles were obtained in moderate to excellent yields.
Based on the results, it is quite clear that the efficiency of
the click reaction is rarely dependent on the electronic na-
ture of the substrates (4aa–ae). The three heterocyclic acet-
ylene compounds reacted smoothly and generated target
compounds in good to excellent yields (4af, 4ag, 4ah); the
obtained products such as 4af was potential bidentate li-
gand for complex formation and catalysis. The 1-ethynyl-
cyclohexan-1-ol generated the desired product 4ai in excel-
lent yield. Notably, aliphatic alkynes were also successfully
converted into the desired products with moderate yields
(4aj, 4ak).
N
CuI, Et2NH
glycerol, r.t.
N
N
NaN3
R2
Ph
R2
X
N
Ph
3
1a
2a
4'
N
N
N
N
N
N
N
N
Ph
Ph
Ph
4ba: 50%
4bb: 74%
4bc: 51%
N
N
N
N
N
N
N
N
N
N
Ph
Ph
Ph
NO2
MeO
4bd: 43%
Cl
4be: 70%
4bf: 99%
N
F
N
N
N
N
N
N
N
F
O
Ph
Ph
F
Ph
F
F
F
F
F
F
N
CuI, Et2NH
glycerol, r.t.
Bn
4bg: 99%
4bh: 98%
4bi: 37%
N
N
R1
NaN3
Bn Br
N
N
R1
N
N
N
N
1
2a
3a
4
Ph
Ph
N
N
N
4bj: 71%
4bk: 51%
N
N
N
N
N
OMe
Bn
N
Scheme 3 Substrate scope of organic halides. Reagents and conditions:
1a (0.24 mmol), 2a (0.24 mmol), 3 (0.20 mmol), catalyst (0.002
mmol), and ligand (0.01 mmol), solvent (1 mL). All reactions were car-
ried out under N2 atmosphere and monitored by HPLC until comple-
tion. Isolated yields are shown. Target compounds 4bb–be and 4bi
were synthesized from benzyl chlorides, the rest of the compounds
were synthesized from organic bromides.
Bn
Bn
Bn
Bn
OMe
4aa: 99%
4ab: 92%
4ac: 94%
N
N
N
N
N
N
N
N
F
N
N
Bn
Bn
Bn
F
4ad: 99%
4ae: 88%
4af: 80%
N
HO
N
N
N
S
N
N
N
N
N
In addition, some reactions were designed using bromo-
benzene and iodobenzene under standard conditions; how-
ever, they did not generate the target compounds. We spec-
ulate that phenyl azides are difficult to generate from ben-
zene halides by nucleophilic substitution, which makes the
target compound difficult to generate (Scheme 4).
N
Bn
4ag: 69%
4ah: 98%
4ai: 97%
N
N
N
N
N
Si
N
Bn
Bn
4aj:51%
4ak: 50%
CuI
N
Et2NH
N
N
Scheme 2 Substrate scope of alkynes. Reagents and conditions: 1 (0.24
mmol), 2a (0.24 mmol), 3a (0.20 mmol), catalyst (0.002 mmol), ligand
(0.01 mmol), solvent (1 mL). All reactions were carried out under N2 atmo-
sphere and monitored by HPLC until completion. Isolated yields are shown.
NaN3
X
glycerol
r.t., 24 h
4*
1a
2a
3*
X = Br, I
The scope of substituents in respect to organic halides
was investigated next as shown in Scheme 3. The substitut-
ed benzyl bromides with electron-withdrawing groups per-
formed better than the ones with electron-donating groups
(4bf–bh vs 4ba). The substituted benzyl chlorides (X = Cl)
were also investigated, and the reactions afforded the cor-
responding compounds smoothly in moderate yields (4bb–
be). As for 4bi, it turned out that steric hindrance signifi-
cantly affected the reaction efficiency. The use of alkyl
bromides gave moderate yields (4bj, 4bk).
Scheme 4 Synthesis of target compound from halobenzene
In order to demonstrate the practical application of this
method, a gram-scale reaction was designed with 5.04
mmol 1a, 5.04 mmol 2a, and 4.2 mmol 3a under the stan-
dard conditions. The corresponding compound 1-benzyl-4-
(4-fluorophenyl)-1H-1,2,3-triazole (4ad) was obtained in
0.99 g (93%). This is a good demonstration for its synthetic
value in organic synthesis (Scheme 5).
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Synthesis
Table 3 Control Experiments for Reaction Mechanism Studya
CuI
Et2NH
N
N
N
F
NaN3
F
Bn Br
NaN3
Ph
glycerol
r.t., 5 h
Bn
1a
1.2 equiv
2a
1.2 equiv
2a
3a
4ad: 93%
1ad
N
CuI, Et2NH
N
N
Scheme 5 Gram-scale preparation of 4ad
glycerol, 16 h
Ph
4ba
In addition, our catalytic system was active with inter-
nal alkynes at the elevated temperature as well, as shown in
Table 2. Thus, electron-rich and electron-poor internal aro-
matic alkynes could react with other substrates to provide
the desired products 4e–f. Heterocyclic aromatic alkynes
also provided the desired compound catalyzed by our cata-
lyst system (4d). However, aliphatic alkynes did not react
with other substrates (4g).
Br
3ba
1.0 equiv
Entry
CuI (equiv)
Et2NH (equiv)
Yield (%)b
1
2
3
4
5
1.0
–
7
23
50
48
51
0.01
0.01
0.01
0.01
–
0.05
1.0
2.0
Table 2 Synthesis of 1,4,5-Trisubstituted 1,2,3-Triazoles from Internal
Alkynesa
a Reaction conditions: 1a (0.24 mmol), 2a (0.24 mmol), 3ba (0.20 mmol),
catalyst (0.002 mmol), ligand (0.01 mmol), solvent (1 mL). All reactions
were carried out under N2 atmosphere and monitored by HPLC until com-
pletion.
N
Bn
N
N
CuI, Et2NH
Bn Br
R
R
NaN3
b Isolated yield.
glycerol,
100 °C,16 h
R
R
4c–g
1c–g
2a
3a
increasing the quantity of CuI reduced the yield of the reac-
tion. Catalytic quantity of ligand (diethylamine) could obvi-
ously improve the catalytic efficiency of CuI, but increasing
the quantity of diethylamine had no obvious effect on the
reaction. According to the above results, we may conjecture
that diethylamine mainly acted as a ligand of CuI but not as
base to the reaction. To verify our hypothesis, CuI and di-
ethylamine were mixed for 10 minutes under an N2 atmo-
sphere, then the remaining diethylamine was removed un-
der high vacuum conditions for 1 hour (Figure 1 A, B). At
the end, we used the residue as catalyst to synthesize 4ba,
this showed almost the same result compared to the opti-
mized reaction condition. Another experiment without di-
ethylamine demonstrated this result, thus CuI showed a
suspended state in glycerol (Figure 1 D). The introduction of
diethylamine could effectively improve the solubility of CuI
Product
R
Yield (%)b
4c
4d
4e
4f
Ph
31
23
25
20
–
2-thienyl
4-FC6H4
4-MeOC6H4
n-Pr
4g
a Reaction conditions: 1c–g (0.24 mmol), 2a (0.24 mmol), 3a (0.20 mmol),
CuI (0.002 mmol), Et2NH (0.01 mmol), glycerol (1 mL). All reactions were
carried out under N2 atmosphere and monitored by HPLC until completion.
b Isolated yield.
To gain insight into the reaction mechanism, several
control experiments were carried out (Table 3). The results
showed that CuI was essential for this reaction; however,
Figure 1 A : Schlenk tube containing CuI and diethylamine without vacuum; B: Schlenk tube containing CuI and diethylamine under vacuum for 1 h,
and then observed under 365 nm UV; C: Contents of Schlenk tube B was mixed with glycerol and stirred for 10 min, and then observed under 365 nm
UV; D: The left Schlenk tube containing CuI, diethylamine, and glycerol was stirred for 10 min. The right Schlenk tube containing CuI and glycerol was
stirred for 10 min.
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Synthesis
by forming the copper-diethylamine complex (Figure 1 B,
C), which may be an important reason to increase the cata-
lytic efficiency.
Table 4 Effect of Solvent on the Reactiona
NaN3
Ph
1a
1.2 equiv
2a
1.2 equiv
Based on these experimental results and previous re-
ports,7b a possible mechanism for this cascade reaction is
outlined in Scheme 6. Most likely, the initial step here is the
formation of the copper complex I from CuI and Et2NH;
meanwhile, organic azide II is formed from the organic ha-
lide and sodium azide by nucleophilic substitution. Then,
copper(I) acetylide is generated from copper complex I and
the alkyne. Subsequently, copper(I) acetylide attacks organ-
ic azides and gives six-membered copper metallacycle III.
Finally, ring contraction affords copper(I) triazolide com-
plex IV, from which the target product is produced by the
release of the catalyst.
N
CuI, Et2NH
N
N
glycerol, 16 h
Ph
4ba
Br
3ba
1.0 equiv
Entry
t-BuOH (mL)
H2O (mL)
Yield (%)b
1
2
3
4
5
1
–
30
28
21
45
33
0.66
0.5
0.33
–
0.33
0.5
0.66
1
CuI + Et2NH
a Reaction conditions: 1a (0.24 mmol), 2a (0.24 mmol), 3ba (0.20 mmol),
catalyst (0.002 mmol), and ligand (0.01 mmol), in solvent. All reactions
were carried out under N2 atmosphere and monitored by HPLC until com-
pletion.
N
R2
R1
N
N
CuL
b Isolated yield.
I
R1
In conclusion, we have developed a new method for the
synthesis of 1,4-disubstituted 1,2,3-triazoles with the cata-
lyst system of CuI/Et2NH using a three-component reaction
of organic halides, terminal acetylenes, and sodium azide.
This protocol provides a simple, cheap, atom- and step-effi-
cient access to 1,4-disubstituted 1,2,3-triazoles. The attrac-
tive features of the reaction involve green solvent glycerol,
excellent functional group tolerance, and mild reaction
conditions.
R1
CuL
N
R2
N
N
R1
CuL
R2
R2
X
NaN3
N
N
N
IV
II
R1
CuL
N
N
N
R2
III
Scheme 6 Proposed mechanism for complex I-catalyzed cycloaddition
1H NMR spectra were recorded at 400 MHz, and 13C NMR spectra
were recorded at 100 MHz (Bruker). 1H NMR chemical shifts (δ) are
reported in ppm relative to TMS with the solvent signal as the inter-
nal standard (CDCl3 at 7.26 ppm). 13C NMR chemical shifts are report-
ed in ppm from TMS with the solvent resonance as the internal stan-
dard (CDCl3 at 77.00 ppm). HPLC analysis used Agilent 1260 HPLC.
Flash column chromatography was carried out using silica gel. High-
resolution mass spectra were obtained with an AB Triple TOF 5600
Plus system. Reactions were monitored by TLC and visualized with ul-
traviolet light. IR spectra were recorded on a Nicolet 6700 on a KBr
beamsplitter.
of terminal alkynes7b
The most important feature of our work is that
CuI/Et2NH-catalyzed synthesis of target compounds in
green solvent glycerol. Compared with other protic solvents
(water, ethanol), glycerol shows excellent results, and it is
likely to be due to the unique solubility of organic com-
pounds. This hypothesis was tested and verified by experi-
ments. Phenylacetylene (1a), sodium azide (2a), and 4-
methylbenzyl bromide (3ba) were selected as reaction sub-
strates, and component solvent in different proportions of
water (poor solubility of organic substrate) and tert-butyl
alcohol (good solubility of organic substrate) were
selected as solvents. It can be seen that the yield of the re-
action varies greatly by changing the proportion of the sol-
vent. In particular, when the ratio of tert-butyl alcohol and
water is 1:2, the yield of the reaction is obviously improved.
This shows that the solubility of the organic substrate in the
solvent has great effect on the result of the reaction (Table 4).
1,2,3-Triazoles; General Procedure
A mixture of alkyne (0.24 mmol), NaN3 (16 mg, 0.24 mmol), and ha-
lide (0.20 mmol) were stirred in glycerol (1.0 mL) in the presence of
CuI (0.38 mg, 0.002 mmol) and Et2NH (0.73 mg, 0.01 mmol) at r.t. in a
Schlenk tube under N2. The progress of the reaction was monitored
by HPLC until the reaction was complete. H2O (10 mL) was added to
the mixture and extracted with acetic ether (3 × 20 mL). The com-
bined organic layers were dried (anhyd Na2SO4) and concentrated.
The residue was subjected to flash column chromatography on silica
gel (petroleum ether/acetic ether) to afford the corresponding com-
pound 4.
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1-Benzyl-4-(4-ethylphenyl)-1H-1,2,3-triazole (4aa)
13C NMR (100 MHz, CDCl3): δ = 150.26, 149.35, 148.75, 136.89,
134.34, 129.18, 128.86, 128.33, 122.86, 121.90, 120.23, 54.40.
HRMS (ESI): m/z [M + H]+ calcd for C14H12N4: 237.1135; found:
237.1137.
Reaction time: 5.5 h; white solid; yield: 52.3 mg (99%); mp 118–119 °C.
1H NMR (400 MHz, CDCl3): δ = 7.71 (d, J = 8.2 Hz, 2 H), 7.62 (s, 1 H),
7.42–7.36 (m, 3 H), 7.33–7.28 (m, 2 H), 7.23 (d, J = 7.9 Hz, 2 H), 5.57 (s,
2 H), 2.66 (q, J = 7.6 Hz, 2 H), 1.24 (t, J = 7.6 Hz, 3 H).
3-(1-Benzyl-1H-1,2,3-triazol-4-yl)pyridine (4ag)
13C NMR (100 MHz, CDCl3): δ = 148.30, 144.44, 134.73, 129.14,
Reaction time: 2.5 h; white solid; yield: 32.7 mg (69%); mp 100–101 °C.
128.76, 128.30, 128.05, 127.89, 125.72, 119.19, 54.25, 28.67, 15.49.
1H NMR (400 MHz, CDCl3): δ = 8.95 (d, J = 2.3 Hz, 1 H), 8.55 (m, 1 H),
HRMS (ESI): m/z [M + H]+ calcd for C17H17N3: 264.1495; found:
8.18 (m, 1 H), 7.76 (s, 1 H), 7.47–7.26 (m, 6 H), 5.60 (s, 2 H).
264.1511.
13C NMR (100 MHz, CDCl3): δ = 149.23, 147.01, 145.15, 134.37,
1-Benzyl-4-(4-methoxyphenyl)-1H-1,2,3-triazole (4ab)
132.99, 129.24, 128.95, 128.13, 126.70, 123.73, 119.86, 54.39.
HRMS (ESI): m/z [M + H]+ calcd for C14H12N4: 237.1135; found:
Reaction time: 5 h; yellow solid; yield: 49.0 mg (92%); mp 143–145 °C.
1H NMR (400 MHz, CDCl3): δ = 7.75–7.69 (m, 2 H), 7.57 (s, 1 H), 7.42–
7.35 (m, 3 H), 7.35–7.28 (m, 2 H), 6.96–6.90 (m, 2 H), 5.56 (s, 2 H),
3.83 (s, 3 H).
237.1131.
1-Benzyl-4-(thiophen-2-yl)-1H-1,2,3-triazole (4ah)
13C NMR (100 MHz, CDCl3): δ = 159.60, 148.11, 134.77, 129.14,
Reaction time: 4 h; white solid; yield: 47.4 mg (98%); mp 118–120 °C.
1H NMR (400 MHz, CDCl3): δ = 7.57 (s, 1 H), 7.42–7.34 (m, 3 H), 7.35–
7.25 (m, 4 H), 7.04 (m, 1 H), 5.54 (s, 2 H).
128.75, 128.05, 127.01, 123.28, 118.67, 114.21, 55.32, 54.21.
HRMS (ESI): m/z [M + H]+ calcd for C16H15N3O: 266.1288; found:
13C NMR (100 MHz, CDCl3): δ = 143.32, 134.53, 132.91, 129.20,
266.1281.
128.87, 128.11, 127.61, 125.07, 124.19, 119.04, 54.29.
1-Benzyl-4-(3-methoxyphenyl)-1H-1,2,3-triazole (4ac)
HRMS (ESI): m/z [M + H]+ calcd for C13H11N3S: 242.0746; found:
Reaction time: 4.5 h; white solid; yield: 50.0 mg (94%); mp 74–75 °C.
242.0746.
1H NMR (400 MHz, CDCl3): δ = 7.65 (s, 1 H), 7.44–7.34 (m, 4 H), 7.33–
7.27 (m, 4 H), 6.86 (m, 1 H), 5.55 (s, 2 H), 3.84 (s, 3 H).
1-(1-Benzyl-1H-1,2,3-triazol-4-yl)cyclohexan-1-ol (4ai)
13C NMR (100 MHz, CDCl3): δ = 160.02, 148.09, 134.68, 131.86,
129.84, 129.16, 128.79, 128.06, 119.73, 118.11, 114.32, 110.70, 55.36,
54.23.
HRMS (ESI): m/z [M + H]+ calcd for C16H15N3O: 266.1288; found:
266.1288.
Reaction time: 3 h; white solid; yield: 50.1 mg (97%); mp 122–124 °C.
1H NMR (400 MHz, CDCl3): δ = 7.37 (d, J = 6.9 Hz, 4 H), 7.30–7.24 (m, 2
H), 5.50 (s, 2 H), 2.29 (s, 1 H), 2.00–1.29 (m, 10 H).
13C NMR (100 MHz, CDCl3): δ = 156.00, 134.61, 129.08, 128.69,
128.09, 119.47, 69.53, 54.14, 38.07, 25.32, 21.92.
HRMS (ESI): m/z [M + H]+ calcd for C15H19N3O: 258.1601; found:
258.1605.
1-Benzyl-4-(4-fluorophenyl)-1H-1,2,3-triazole (4ad)
Reaction time: 4.5 h; white solid; yield: 50.3 mg (99%); mp 110–112 °C.
1H NMR (400 MHz, CDCl3): δ = 7.80–7.73 (m, 2 H), 7.62 (s, 1 H), 7.38
1-Benzyl-4-cyclopropyl-1H-1,2,3-triazole (4aj)
(m, 3 H), 7.31 (m, 2 H), 7.13–7.04 (m, 2 H), 5.56 (s, 2 H).
Reaction time: 5 h; white solid; yield: 20.4 mg (51%); mp 44–45 °C.
13C NMR (100 MHz, CDCl3): δ = 162.85, 160.39, 146.33, 133.56,
128.15, 127.80, 127.05, 126.44, 126.36, 125.76, 125.73, 118.21,
114.85, 114.63, 53.24.
HRMS (ESI): m/z [M + H]+ calcd for C15H12FN3: 254.1088; found:
254.1078.
1H NMR (400 MHz, CDCl3): δ = 7.27 (d, J = 6.7 Hz, 3 H), 7.19–7.13 (m, 2
H), 7.07 (s, 1 H), 5.37 (s, 2 H), 1.83 (m, 1 H), 0.88–0.76 (m, 2 H), 0.76–
0.68 (m, 2 H).
13C NMR (100 MHz, CDCl3): δ = 149.61, 133.89, 128.00, 127.56,
126.95, 118.60, 52.96, 6.70, 5.69.
HRMS (ESI): m/z [M + H]+ calcd for C12H13N3: 200.1182; found:
200.1182.
1-Benzyl-4-(2-fluorophenyl)-1H-1,2,3-triazole (4ae)
Reaction time: 3 h; white solid; yield: 44.7 mg (88%); mp 96–97 °C.
1H NMR (400 MHz, CDCl3): δ = 8.23 (m, 1 H), 7.79 (d, J = 3.7 Hz, 1 H),
1-Benzyl-4-(triethylsilyl)-1H-1,2,3-triazole (4ak)
7.29 (m, 3 H), 7.26–7.13 (m, 4 H), 7.02 (m, 1 H), 5.52 (s, 2 H).
Reaction time: 4 h; light yellow liquid; yield: 27.4 mg (50%).
13C NMR (100 MHz, CDCl3): δ = 159.38, 156.92, 140.61, 133.65,
128.31, 128.23, 128.10, 127.72, 126.94, 126.77, 126.73, 123.57,
123.54, 121.70, 121.57, 117.58, 117.45, 114.69, 114.47, 53.18.
HRMS (ESI): m/z [M + H]+ calcd for C15H12FN3: 254.1088; found:
254.1087.
1H NMR (400 MHz, CDCl3): δ = 7.50 (s, 1 H), 7.38–7.31 (m, 3 H), 7.24
(m, 2 H), 5.56 (s, 2 H), 1.01–0.95 (m, 9 H), 0.85–0.77 (m, 6 H).
13C NMR (100 MHz, CDCl3): δ = 143.09, 134.06, 128.61, 127.98,
127.48, 126.86, 52.41, 6.29, 2.46.
HRMS (ESI): m/z [M + H]+ calcd for C15H23N3Si: 274.1734; found:
274.1746.
2-(1-Benzyl-1H-1,2,3-triazol-4-yl)pyridine (4af)
Reaction time: 3 h; white solid; yield: 37.9 mg (80%); mp 115–116 °C.
1-(4-Methylbenzyl)-4-phenyl-1H-1,2,3-triazole (4ba)
1H NMR (400 MHz, CDCl3): δ = 8.58–8.50 (m, 1 H), 8.17 (d, J = 8.0, 1.1
Hz, 1 H), 8.04 (s, 1 H), 7.76 (m, 1 H), 7.42–7.29 (m, 5 H), 7.20 (m, 1 H),
5.58 (s, 2 H).
Reaction time: 4 h; white solid; yield: 25.0 mg (50%); mp 95–96 °C.
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1H NMR (400 MHz, CDCl3): δ = 7.82–7.76 (m, 2 H), 7.63 (s, 1 H), 7.43–
7.36 (m, 2 H), 733–7.27 (m, 1 H), 7.24–7.14 (m, 4 H), 5.53 (s, 2 H), 2.36
(s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 147.11, 137.71, 130.61, 129.56,
128.78, 127.74, 127.10, 127.08, 124.65, 118.34, 53.02, 20.14.
1-(4-Fluorobenzyl)-4-phenyl-1H-1,2,3-triazole (4bg)
Reaction time: 5 h; white solid; yield: 49.7 mg (99%); mp 123–125 °C.
1H NMR (400 MHz, CDCl3): δ = 7.79 (d, J = 7.3 Hz, 2 H), 7.66 (s, 1 H),
7.40 (t, J = 7.5 Hz, 2 H), 7.35–7.27 (m, 3 H), 7.07 (t, J = 8.5 Hz, 2 H), 5.53
(s, 2 H).
13C NMR (100 MHz, CDCl3): δ = 164.11, 161.64, 148.31, 130.56,
130.53, 130.39, 129.98, 129.90, 128.83, 128.81, 128.26, 125.72,
119.42, 116.26, 116.05, 53.50.
HRMS (ESI): m/z [M + H]+ calcd for C16H15N3: 250.1339; found:
250.1333.
1-Benzyl-4-phenyl-1H-1,2,3-triazole (4bb)
HRMS (ESI): m/z [M + H]+ calcd for C15H12FN3: 254.1088; found:
Reaction time: 5 h; white solid; yield: 39.4 mg (74%); mp 129–130 °C.
254.1091
1H NMR (400 MHz, CDCl3): δ = 7.83–7.76 (m, 2 H), 7.66 (s, 1 H), 7.44–
7.35 (m, 5 H), 7.31 (m, 3 H), 5.58 (s, 2 H).
1-[(Perfluorophenyl)methyl]-4-phenyl-1H-1,2,3-triazole (4bh)
13C NMR (100 MHz, CDCl3): δ = 147.21, 133.65, 129.50, 128.13,
Reaction time: 5 h; white solid; yield: 63.9 mg (98%); mp 158–160 °C.
1H NMR (400 MHz, CDCl3): δ = 7.86–7.76 (m, 3 H), 7.41 (m, 2 H), 7.34
(m, 1 H), 5.67 (s, 2 H).
127.77, 127.13, 127.03, 124.67, 118.44, 53.21.
HRMS (ESI): m/z [M + H]+ calcd for C15H13N3: 236.1282; found:
13C NMR (100 MHz, CDCl3): δ = 148.48, 130.06, 128.89, 128.47,
266.1280.
125.80, 119.58, 40.90.
1-(3-Methylbenzyl)-4-phenyl-1H-1,2,3-triazole (4bc)
HRMS (ESI): m/z [M + H]+ calcd for C15H8F5N3: 326.0711; found:
Reaction time: 6 h; light yellow solid; yield: 25.5 mg (51%); mp 96–97 °C.
326.0711.
1H NMR (400 MHz, CDCl3): δ = 7.80 (d, J = 7.5 Hz, 2 H), 7.65 (s, 1 H),
7.39 (t, J = 7.3 Hz, 2 H), 7.28 (m, 2 H), 7.20–7.07 (m, 3 H), 5.53 (s, 2 H),
2.34 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 148.17, 139.01, 134.56, 130.56,
129.51, 129.00, 128.77, 128.75, 128.11, 125.68, 125.12, 119.45, 54.23,
21.32.
4-Phenyl-1-[2-(trifluoromethoxy)benzyl]-1H-1,2,3-triazole (4bi)
Reaction time: 16 h; light yellow solid; yield: 23.7 mg (37%); mp 94–
95 °C.
1H NMR (400 MHz, CDCl3): δ = 7.82 (d, J = 7.6 Hz, 2 H), 7.73 (s, 1 H),
7.42 (t, J = 7.4 Hz, 3 H), 7.32 (m, 4 H), 5.68 (s, 2 H).
13C NMR (100 MHz, CDCl3): δ = 146.88, 130.41, 130.39, 130.34,
128.84, 128.28, 127.55, 127.47, 125.76, 121.83, 120.69, 120.68,
119.78, 48.41.
HRMS (ESI): m/z [M + H]+ calcd for C16H15N3: 250.1339; found:
250.1344.
1-(3-Methoxybenzyl)-4-phenyl-1H-1,2,3-triazole (4bd)
HRMS (ESI): m/z [M + H]+ calcd for C16H12F3N3O: 320.1005; found:
Reaction time: 5 h; white solid; yield: 22.9 mg (43%); mp 84–85 °C.
320.1020.
1H NMR (400 MHz, CDCl3): δ = 7.76–7.70 (m, 2 H), 7.60 (s, 1 H), 7.37–
7.29 (m, 2 H), 7.28–7.18 (m, 2 H), 6.83 (m, 2 H), 6.76 (m, 1 H), 5.47 (s,
2 H), 3.71 (s, 3 H).
1-(Cyclopropylmethyl)-4-phenyl-1H-1,2,3-triazole (4bj)
Reaction time: 10 h; white solid; yield: 28.4 mg (71%); mp 80–82 °C.
13C NMR (100 MHz, CDCl3): δ = 159.13, 147.20, 135.08, 129.50,
129.20, 127.77, 127.13, 124.67, 119.23, 118.46, 113.24, 112.63, 54.30,
53.16.
HRMS (ESI): m/z [M + H]+ calcd for C16H15N3O: 266.1288; found:
266.1283.
1H NMR (400 MHz, CDCl3): δ = 7.90–7.80 (m, 3 H), 7.42 (t, J = 7.6 Hz, 2
H), 7.33 (t, J = 7.4 Hz, 1 H), 4.25 (s, 2 H), 1.34 (m, 1 H), 0.72 (m, 2 H),
0.47 (m, 2 H).
13C NMR (100 MHz, CDCl3): δ = 143.53, 126.55, 124.57, 123.81,
121.47, 114.80, 50.80, 25.46, 6.87.
HRMS (ESI): m/z [M + H]+ calcd for C12H13N3: 200.1182; found:
200.1187.
1-(4-Nitrobenzyl)-4-phenyl-1H-1,2,3-triazole (4be)
Reaction time: 5 h; white solid; yield: 39.4 mg (70%); mp 160–161 °C.
1H NMR (400 MHz, CDCl3): δ = 8.21 (d, J = 8.4 Hz, 2 H), 7.82–7.78 (m, 2
H), 7.76 (s, 1 H), 7.46–7.38 (m, 4 H), 7.33 (t, J = 7.4 Hz, 1 H), 5.69 (s, 2 H).
13C NMR (100 MHz, CDCl3): δ = 148.69, 148.08, 141.75, 130.08,
1-Butyl-4-phenyl-1H-1,2,3-triazole (4bk)
Reaction time: 10 h; light yellow solid; yield: 20.4 mg (51%); mp 47–
48 °C.
1H NMR (400 MHz, CDCl3): δ = 7.86–7.80 (m, 2 H), 7.74 (s, 1 H), 7.42
(m, 2 H), 7.36–7.30 (m, 1 H), 4.40 (t, J = 7.2 Hz, 2 H), 1.93 (m, 2 H),
1.46–1.35 (m, 2 H), 0.97 (t, J = 7.4 Hz, 3 H).
128.92, 128.56, 128.50, 125.75, 124.32, 119.78, 53.20.
HRMS (ESI): m/z [M + H]+ calcd for C15H12N4O2: 281.1033; found:
281.1041
13C NMR (100 MHz, CDCl3): δ = 147.73, 130.75, 128.81, 128.06,
1-(3-Chlorobenzyl)-4-phenyl-1H-1,2,3-triazole (4bf)
125.69, 119.38, 50.15, 32.32, 19.74, 13.47.
HRMS (ESI): m/z [M + H]+ calcd for C12H15N3: 202.1339; found:
Reaction time: 6 h; white solid; yield: 54.9 mg (99%); mp 165–167 °C.
1H NMR (400 MHz, CDCl3): δ = 7.85–7.78 (m, 2 H), 7.70 (s, 1 H), 7.46–
202.1347.
7.37 (m, 2 H), 7.38–7.29 (m, 4 H), 7.18 (m, 1 H), 5.55 (s, 2 H).
1-Benzyl-4,5-diphenyl-1H-1,2,3-triazole (4c)
13C NMR (100 MHz, CDCl3): δ = 148.45, 136.62, 135.07, 130.46,
Reaction time: 16 h; white solid; yield: 19.4 mg (31%); mp 99–100 °C.
130.34, 129.01, 128.84, 128.30, 128.08, 126.05, 125.73, 119.49, 53.52.
1H NMR (400 MHz, CDCl3): δ = 7.58–7.54 (m, 2 H), 7.50–7.39 (m, 3 H),
7.29–7.22 (m, 6 H), 7.15 (d, J = 7.0 Hz, 2 H), 7.03 (m, 2 H), 5.41 (s, 2 H).
HRMS (ESI): m/z [M + H]+ calcd for C15H12ClN3: 270.0793; found:
270.0787.
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13C NMR (100 MHz, CDCl3): δ = 143.45, 134.28, 132.89, 129.76,
129.08, 128.68, 128.14, 127.67, 127.42, 127.13, 126.78, 126.71,
126.48, 125.71, 51.06.
Genaz-zani, A. A. J. Med. Chem. 2006, 49, 467. (c) Angell, Y. L.;
Burgess, K. Chem. Soc. Rev. 2007, 36, 1674. (d) Meldal, M.;
Tornoe, C. W. Chem. Rev. 2008, 108, 2952.
(2) (a) Bock, V. D.; Speijer, D.; Hiemstra, H.; van Maarseveen, J. H.
Org. Biomol. Chem. 2007, 5, 971. (b) Dedola, S.; Nepogodiev, S.
A.; Field, R. A. Org. Biomol. Chem. 2007, 5, 1006.
(3) For selected examples: (a) Wu, P.; Feldman, A. K.; Nugent, A. K.;
Hawker, C. J.; Scheel, A.; Voit, B.; Pyun, J.; Fréchet, J. M. J.;
Sharpless, K. B.; Fokin, V. V. Angew. Chem. Int. Ed. 2004, 43,
3928. (b) Nandivada, H.; Jiang, X. W.; Lahann, J. Adv. Mater.
2007, 19, 2197. (c) Johnson, T. C.; Totty, W. G.; Wills, M. Org.
Lett. 2012, 14, 5230.
HRMS (ESI): m/z [M + H]+ calcd for C21H17N3: 312.1495; found:
312.1496.
1-Benzyl-4,5-di(thiophen-2-yl)-1H-1,2,3-triazole (4d)
Reaction time: 16 h; light yellow solid; yield: 14.9 mg (23%); mp 132–
133 °C.
1H NMR (400 MHz, CDCl3): δ = 7.56 (d, J = 5.1 Hz, 1 H), 7.28–7.23 (m, 3
H), 7.21 (d, J = 5.1 Hz, 1 H), 7.13 (m, 2 H), 7.06 (m, 2 H), 6.97 (d, J = 3.6
Hz, 1 H), 6.94 (m, 1 H), 5.44 (s, 2 H).
(4) For selected examples: (a) Kolb, H. C.; Sharpless, K. B. Drug.
Discov. Today 2003, 8, 1128. (b) Sugawara, A.; Sunazuka, T.;
Hirose, T.; Nagai, K.; Yamaguchi, Y.; Hanaki, H.; Sharpless, K. B.;
Omura, S. Bioorg. Med. Chem. Lett. 2007, 17, 6340. (c) Tron, G. C.;
Pirali, T.; Billington, R. A.; Canonico, P. L.; Sorba, G.; Genazzani,
A. A. Med. Res. Rev. 2008, 28, 278.
13C NMR (100 MHz, CDCl3): δ = 141.16, 133.99, 131.54, 130.13,
128.72, 127.67, 127.18, 126.83, 126.37, 126.25, 125.01, 124.51,
124.40, 123.69, 51.22.
HRMS (ESI): m/z [M + H]+ calcd for C17H13N3S2: 324.0624; found:
324.0632.
(5) For selected examples, see ref. 1d and: (a) Dai, Q.; Gao, W.; Liu,
D.; Kapzes, L. M.; Zhang, X. J. Org. Chem. 2006, 71, 3928. (b) Liu,
Y. X.; Yan, W. M.; Chen, Y. F.; Petersen, J. L.; Shi, X. D. Org. Lett.
2008, 10, 5389.
(6) For selected examples: (a) Meldal, M.; Christensen, C. C.;
Tornøe, W. J. Org. Chem. 2002, 67, 3057. (b) Li, Z.; Seo, T. S.; Ju, J.
Tetrahedron Lett. 2004, 45, 3143. (c) Zhang, L.; Chen, X.; Xue, P.;
Sun, H. H. Y.; Williams, I. D.; Sharpless, K. B.; Fokin, V. V.; Jia, G.
J. Am. Chem. Soc. 2005, 127, 15998. (d) Golas, P. L.; Tsarevsky, N.
V.; Sumerlin, B. S.; Matyjaszewski, K. Macromolecules. 2006, 39,
6451. (e) Kwok, S. W.; Fotsing, J. R.; Fraser, R. J.; Rodionov, V. O.;
Fokin, V. V. Org. Lett. 2010, 12, 4217.
1-Benzyl-4,5-bis(4-fluorophenyl)-1H-1,2,3-triazole (4e)
Reaction time: 16 h; white solid; yield: 17.4 mg (25%); mp 82–83 °C.
1H NMR (400 MHz, CDCl3): δ = 7.53–7.47 (m, 2 H), 7.26 (m, 3 H), 7.12–
7.07 (m, 4 H), 7.03–6.99 (m, 2 H), 6.95 (m, 2 H), 5.39 (s, 2 H).
13C NMR (100 MHz, CDCl3): δ = 164.67, 163.62, 162.18, 161.16,
143.98, 135.13, 132.62, 132.11, 132.02, 128.78, 128.45, 128.37,
128.28, 127.39, 126.92, 126.88, 123.57, 123.54, 116.66, 116.44,
115.60, 115.39, 52.18.
HRMS (ESI): m/z [M + H]+ calcd for C21H16F2N3: 348.1307; found:
348.1303.
(7) For selected examples, see ref. 1d and: (a) Kolb, H. C.; Finn, M.
G.; Sharpless, K. B. Angew. Chem. Int. Ed. 2001, 40, 2004.
(b) Rostovtsev, V. V.; Green, L. G.; Fokin, V. V.; Sharpless, K. B.
Angew. Chem. Int. Ed. 2002, 41, 2596. (c) Rodionov, V. O.; Fokin,
V. V.; Finn, M. G. Angew. Chem. Int. Ed. 2005, 44, 2210.
(d) Debets, M. F.; van Berkel, S. S.; Dommerholt, J.; Dirks, A. J.;
Rutjes, F. P. J. T.; van Delft, F. L. Acc. Chem. Res. 2011, 44, 805.
(8) Scriven, E. F. V.; Turnbull, K. Chem. Rev. 1988, 88, 297.
(9) For selected examples: (a) Feldman, A. K.; Colasson, B.; Fokin, V.
V. Org. Lett. 2004, 6, 3897. (b) Baig, R. B. N.; Varma, R. S. Chem.
Commun. 2012, 48, 5853. (c) Mukherjee, N.; Ahammed, S.;
Bhadra, S.; Ranu, B. C. Green Chem. 2013, 15, 389. (d) Wei, F.; Li,
H.; Song, C.; Ma, Y.; Zhou, L.; Tung, C.; Xu, Z. Org. Lett. 2015, 17,
2860.
1-Benzyl-4,5-bis(4-methoxyphenyl)-1H-1,2,3-triazole (4f)
Reaction time: 16 h; light yellow liquid; yield: 14.8 mg (20%).
1H NMR (400 MHz, CDCl3): δ = 7.50 (d, J = 8.7 Hz, 2 H), 7.28–7.21 (m, 3
H), 7.04 (d, J = 8.3 Hz, 4 H), 6.92 (d, J = 8.6 Hz, 2 H), 6.80 (d, J = 8.7 Hz,
2 H), 5.38 (s, 2 H), 3.85 (s, 3 H), 3.76 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 160.43, 159.60, 144.75, 134.77,
133.78, 132.96, 129.14, 128.58, 128.32, 127.55, 124.88, 120.26,
116.13, 114.99, 55.95, 55.51, 52.25.
HRMS (ESI): m/z [M + H]+ calcd for C23H22N3O2: 372.1707; found:
372.1713.
(10) For selected examples: (a) Liu, P. N.; Siyang, H. X.; Zhang, L.; San
Tse, S. K.; Jia, G. J. Org. Chem. 2012, 77, 5844. (b) Ali, A.; Correa,
A. G.; Alves, D.; Zukerman-Schpector, J.; Westermann, B.;
Ferreira, M. A. B.; Paixao, M. W. Chem. Commun. 2014, 50,
11926. (c) Shil, A. K.; Kumar, S.; Sharma, S.; Chaudhary, A.; Das,
P. RSC Adv. 2015, 5, 11506.
Funding Information
This research was supported by College of Chemistry and Chemical
Engineering, Henan University, and Institute of Chemistry Co. Ltd.,
Henan Academy of Sciences.
)(
(11) Capello, C.; Fisher, U.; Kungerbühler, K. Green Chem. 2007, 9,
927.
(12) Radatz, C. S.; Soares, L. A.; Vieira, E. R.; Alves, D.; Russowsky, D.;
Schneider, P. H. New J. Chem. 2014, 38, 1410.
(13) Tasca, E.; Sorella, G.; Sperni, L.; Strukul, G.; Scarso, A. Green
Chem. 2015, 17, 1414.
Supporting Information
Supporting information for this article is available online at
https://doi.org/10.1055/s-0036-1591557.
S
u
p
p
ortiInfogrmoaitn
S
u
p
p
ortioInfgrmoaitn
(14) Alonso, F.; Moglie, Y.; Radivoy, G.; Yus, M. J. Org. Chem. 2011, 76,
8394.
(15) For selected examples: (a) DeSimone, J. M. Science 2002, 297,
799. (b) Nelson, W. M. Green Solvents for Chemistry: Perspectives
and Practice; Oxford University Press: New York, 2003. (c) Clark,
J. H.; Taverner, S. J. Org. Process Res. Dev. 2007, 11, 149.
References
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D.; Ghadiri, M. R. J. Am. Chem. Soc. 2004, 126, 15366. (b) Pagliai,
F.; Pirali, T.; Grosso, E. D.; Brisco, R. D.; Tron, G. C.; Sorba, G.;
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–I

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S. Guo et al.
Paper
Synthesis
(16) (a) Gu, Y.; Barrault, J.; Jérôme, F. Adv. Synth. Catal. 2008, 350,
2007. (b) Gu, Y.; De Sousa, R.; Frapper, G.; Bachmann, C.;
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B. Org. Lett. 2009, 11, 3024. (b) Alonso, F.; Moglie, Y.; Radivoy,
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© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–I