One-pot, three-component synthesis of 1-(2-hydroxyethyl)-1H-1,2,3-triazole derivatives by copper-catalyzed 1,3-dipolar cycloaddition of 2-azido alcohols and terminal alkynes under mild conditions in water

Article abstract of DOI:10.1002/hlca.200900226

A safe, efficient, and improved procedure for the regioselective synthesis of 1-(2-hydroxyethyl)-1H-1,2,3-triazole derivatives under ambient conditions is described. Terminal alkynes reacted with oxiranes and NaN₃ in the presence of a copper(I)

Full text of DOI:10.1002/hlca.200900226

Helvetica Chimica Acta – Vol. 93 (2010)
435
One-Pot, Three-Component Synthesis of 1-(2-Hydroxyethyl)-1H-1,2,3-
triazole Derivatives by Copper-Catalyzed 1,3-Dipolar Cycloaddition of
2-Azido Alcohols and Terminal Alkynes under Mild Conditions in Water
by Hashem Sharghi*a), Mona Hosseini-Sarvaria), Fatemeh Moeinia), Reza Khalifehb), and
Alireza Salimi Benic)
a) Department of Chemistry, Shiraz University, Shiraz 71454, I. R. Iran
(e-mail: shashem@susc.ac.ir)
b) Department of Chemistry, Shiraz University of Technology, Shiraz 71555-313, I. R. Iran
c) Department of Chemistry, Yasouj University, Yasouj, 75918-74831, I. R. Iran
A safe, efficient, and improved procedure for the regioselective synthesis of 1-(2-hydroxyethyl)-1H-
1,2,3-triazole derivatives under ambient conditions is described. Terminal alkynes reacted with oxiranes
and NaN3 in the presence of a copper(I) catalyst, which is prepared by in situ reduction of the copper(II)
complex 4 with ascorbic acid, in H2O. The regioselective reactions exclusively gave the corresponding 1,4-
disubstituted 1H-1,2,3-triazoles in good to excellent yields. This procedure avoids the handling of organic
azides as they are generated in situ, making this already powerful click process even more user-friendly
and safe. The remarkable features of this protocol are high yields, very short reaction times, a cleaner
reaction profile in an environmentally benign solvent (H2O), its straightforwardness, and the use of
nontoxic catalysts. Furthermore, the catalyst could be recovered and recycled by simple filtration of the
reaction mixture and reused for ten consecutive trials without significant loss of catalytic activity. No
metal-complex leaching was observed after the consecutive catalytic reactions.
Introduction. – Huisgenꢀs 1,3-dipolar cycloaddition of an organic azide and an
alkyne is an efficacious way for multifarious syntheses of the 1H-1,2,3-triazole ring
system [1]. This reaction has important uses in bio-orthogonal bioconjugation [2 – 5],
polymer [6][7] and dendrimer syntheses [8], and the construction of peptide-bond
surrogates [9] and powerful pharmacophores. The reaction takes place in the presence
of a copper(I) catalyst to afford the 1,4-disubstituted 1H-1,2,3-triazoles exclusively,
which contrasts with the thermal reaction requiring high temperature and, prolonged
reaction time and resulting in the two regioisomeric 1,4- and 1,5-disubstituted 1H-1,2,3-
triazoles. The copper(I) catalysts are directly formed from CuI salts in the presence of
ligands [5][10], or prepared in situ by reduction of CuII salts with ascorbate [11], or
oxidation of copper(0) metal [12], or by comproportionation of Cu0 and CuII [13].
The development of heterogeneous catalysts for the synthesis of fine chemicals has
become a major area of research recently, as the potential advantages of these materials
over homogeneous systems can have a major impact on the environmental perform-
ance of a synthesis [14]. To improve the recovery and reuse, copper species have been
immobilized onto various supports such as activated carbon [15], amine-functionalized
polymers [16], zeolites [17], amine-functionalized silica [18], and aluminium oxy-
hydroxide fiber [19].
ꢁ 2010 Verlag Helvetica Chimica Acta AG, Zꢂrich

436
Helvetica Chimica Acta – Vol. 93 (2010)
Although organic azides are generally stable under most reaction conditions such as
in the presence of H2O and O2 [20], isolation or purification of low-molecular-mass
organic azides or polyazides can be problematic. Therefore, a procedure that avoids
isolation of organic azides is desirable. Recently, some examples were reported for in
situ generation of organic azides by means of a one-pot procedure to prepare 1H-1,2,3-
triazole derivatives based on three-component coupling reaction [18][21].
Since 1-(2-hydroxyethyl)-1H-1,2,3-triazole derivatives have become increasingly
useful and important in drugs and pharmaceuticals [22], the development of a simple
and efficient method for their synthesis in a single-step operation is desirable. Here, we
wish to report an efficient, safe, and environmentally benign one-pot synthesis of 1-(2-
hydroxyethyl)-1H-1,2,3-triazole derivatives from oxiranes, NaN3, and alkynes in H2O
in the presence of catalytic amounts of a heterogeneous CuII complex by way of a three-
component reaction, proceeding via the formation of 2-azido alcohols from the
oxiranes and NaN3. Pleasantly, azides generated in situ from the corresponding
oxiranes led efficiently to triazoles.
Results and Discussion. – As part of our continuing attempts to broaden the scope
of heterogeneous catalyst and transition-metal complexes [23], we recently reported
the efficiency of a copper complex in the synthesis of benzimidazole derivatives [24].
The extraordinary stability of this complex toward heat, oxygen, and moisture
prompted us to test them in the Huisgen cycloaddition. Three simple steps were
required to prepare [Cu(bhppda)H2O] (4) from 1 via 2 and 3, as [24] shown in
Scheme 1 (bhppda ¼ N2,N6-bis(2-hydroxyphenyl)pyridine-2,6-dicarboxamidato(2ꢀ).
Scheme 1
To establish the optimum conditions for the Huisgen 1,3-dipolar cycloaddition,
initially, various metal complexes were examined in a model reaction between styrene
oxide (¼2-phenyloxirane; 5a), NaN3, ascorbic acid, and phenylacetylene

Helvetica Chimica Acta – Vol. 93 (2010)
437
(¼ethynylbenzene; 6a) in H2O as solvent at room temperature via a three-component
reaction (Scheme 2).
Scheme 2
The copper complex 4 was found to be the most effective catalyst in terms of
reaction rate, regioselectivity, and yield of the product (Table 1, Entry 1). The reaction
proceeded smoothly to give the corresponding (2-hydroxyethyl)triazole 7a in high
yield. In addition, [Cu(OAc)2] [25] and [Cu(II)(salen)] were also examined as catalysts
for this reaction; however, they were less effective compared to 4 and afforded 7a in
10% and 75% yields, respectively, thereby indicating the important role of the ligand
system (Entries 6 and 7). The attempts to carry out the reaction without a copper
catalyst did not give the expected triazole, even after long reaction times (Entry 8). In
the absence of ascorbic acid, the reaction time increased (Entry 9).
Table 1. Investigation of Various Metal Complexes (5 mol-%) in the Synthesis of 1-(2-Hydroxyethyl)-1H-
1,2,3-triazole Derivative 7a from 2-Phenyloxirane (5a; 1 mmol), Phenylacetylene (6a; 1 mmol), NaN3
(1.2 mmol), and Ascorbic Acid (0.2 mmol) in H2O at Room Temperature
Entry
Catalyst
Time [h]
Yield of 7aa) [%]
1
2
3
4
5
6
7
8
9
[Cu(bhppda)H2O] (4)
[Mn(bhppda)H2O]
[Co(bhppda)H2O]
[Cd(bhppda)H2O]
[Fe(bhppda)H2O]
[Cu(OAc)2]
2
7
7
7
7
7
7
24
7
90
40
–
–
20
10
75
–
[Cu(II)(salen)]
–b)
–c)
45
a) Yield of isolated product. b) Under the same conditions, but without catalyst. c) Under the same
conditions in the presence of 4, but in the absence of ascorbic acid.
Then, we turned our attention to the investigation of the effect of the solvent on our
t
model reaction (Table 2). Organic solvents such as MeCN, DMF, THF, BuOH, and
toluene were not effective (Entries 1 – 5). By changing the solvent to DMSO, which
enhances the solubility of NaN3, the product was obtained in only 10% yield (Entry 6).
However, when the reaction was carried out in the 1:1 mixture of an organic solvent
and H2O, we observed formation of the triazole in 45% and 40% yield after 5 h
(Entries 7 and 8). Pleasantly, a strong acceleration and an excellent yield were observed
in H2O (Entry 9). This is probably due to the high solubility of ascorbic acid and NaN3
in H2O. It should be noted that the optimal catalyst loading in the synthesis of 7a is at a
concentration of 5 mol-%.

438
Helvetica Chimica Acta – Vol. 93 (2010)
Table 2. Investigation of the Effect of Various Solvents on the Synthesis of 1-(2-Hydroxyethyl)-1H-1,2,3-
triazole Derivative 7a from 2-Phenyloxirane (5a; 1 mmol), Phenylacetylene (6a; 1 mmol), NaN3
(1.2 mmol), Ascorbic Acid (0.2 mmol), and Catalyst 4 (5 mol-%) at Room Temperature
Entry Solvent Time [h] Yield of 7aa) [%] Entry Solvent
Time [h] Yield of 7aa) [%]
1
2
3
4
5
MeCN
DMF
THF
tBuOH
toluene
5
5
5
5
5
trace
6
7
8
9
DMSO
5
5
5
2
10
45
40
90
5
5
5
–
DMSO/H2O
tBuOH/H2O
H2O
a) Yield of isolated product.
To generalize the methodology, we focused our attention on the use of other
oxiranes 5 and alkynes 6 that can act as substrates for the synthesis of 1,4-disubstituted
1H-1,2,3-triazoles of type 7. For this purpose, also new alkynes containing thioxanthone
(see 6h and 6i), anthraquinone (see 6o), azacrown ether (see 6n), etc., were
synthesized. As expected, all reactions of 6 with 5a proceeded smoothly at room
temperature and led to the regioselective formation of the desired (2-hydroxyalkyl)-
triazoles 7 in good to excellent yield (Table 3, Entries 2 – 15). In this study, aryl
propargyl ethers (¼ prop-2-yn-1-yloxy)benzenes) 6b – 6e were chosen to investigate
not only the influence of the aryloxy linkage in the coupling by changing the electronic
nature of the alkyne but also as a way to obtain new 1-(2-hydroxyalkyl)-1H-1,2,3-
triazoles. In these cases, the assembly proceeded to completion in reaction times no
longer than 4 h leading to the 1,4-disubstituted 1,2,3-triazoles 7b – 7e with high yields
(Table 3, Entries 2 – 5). As a second approach for the synthesis of new 1-(2-
hydroxyalkyl)-1H-1,2,3-triazoles, the propargylamines 6f and 6g were used in the
cycloaddition reaction with 5a and NaN3, leading to 7f and 7g with similarly good
results (Entries 6 and 7). In a similar manner, propargyloxyheteroarene derivatives
gave the corresponding products 7h – 7j in high yields (Entries 8 – 10). The method-
ology was also applied to the aliphatic alkynes 6k – 6m. For example, the sterically
bulky 6l (Entry 12) reacted without any problems to give the corresponding triazole 7l
in 80% yield. A sterically hindered propargylamine, i.e., the azacrown ether derivative
6n, allowed, through our methodology, to prepare a new azacrown ether that is
attached to 1-(2-hydroxyethyl)-1H-1,2,3-triazole (Entry 14). The 1,3-dipolar Huisgen
cycloaddition reaction was also applicable to substrates containing two reactive sites
such as bis(propargyloxy)anthraquinone 6o, which furnished the corresponding
product 7o in good yield (Entry 15).
Encouraged by the results achieved with 2-phenyloxirane (5a), we turned our
attention to various other oxiranes (Table 3, Entries 16 – 19). The formed triazoles from
the aliphatic oxiranes 5b and 5c were also obtained from the terminal attack of the
azide nucleophile (Entries 16 and 17). The 2-cyclohexyloxirane (5d) also reacted with
NaN3 and phenylacetylene (6a) or propargyl ether 6p to produce the 1-cyclohexyl-1H-
triazole 7r or 7s, respectively, in excellent yield (Entries 18 and 19); the configuration of
the products was found to be trans from the coupling constants of the cyclohexane H-
atoms [26].

Helvetica Chimica Acta – Vol. 93 (2010)
439
As expected, disubstituted alkynes, e.g., 6q and 6r, did not react; this behavior is in
agreement with a mechanism involving the formation of a copper(I) acetylide species
(Table 3, Entries 20 and 21).
To check the feasibility of this procedure on a preparative scale, we carried out the
cycloaddition of 2-phenyloxirane (5a) and NaN3 with phenylacetylene (6a) on a 30-
mmol scale in the presence of CuII complex 4. As expected, the reaction proceeded
similarly to the experiment on a smaller scale, except that a little prolonged reaction
time was required (2.3 h).
To confirm that this process is heterogeneous, the catalyst 4 and the product 7a were
separated by simple filtration, and the solid mixture was washed with excess of AcOEt
to remove the product from the catalyst. This catalyst was directly used for further
recycling experiments. From Table 4, it is very clear that the catalytic activity of the
present system is intact even after 10 cycles.
The proposed mechanism for the formation of 1-(2-hydroxyethyl)-1H-1,2,3-
triazoles may comprise two possible pathways in which the copper complex has a
dual catalytic role: A and B. Pathway A includes the copper-complex-catalyzed 2-azido-
1-phenylethanol formation from NaN3 and 2-phenyloxirane (5a; Scheme 3). The
participation of a metal azide as the catalytically active species suggests that the
mechanism of oxirane-ring opening involves azide delivery from the catalyst as well as
oxirane activation by the Cu catalyst. We propose a mechanism involving catalyst
activation of both nucleophile and electrophile. Moreover, based on our previous
studies [27], it can be concluded that the reaction rate in the present reaction should be
affected not only by complexation of NaN3 with copper complex, but also by
dissociation of the Nꢀ3 anion from the adduct and simultaneous activation of the oxirane
and azide by two different catalyst molecules.
For Pathway B, firstly the ꢃcopper(II)/ascorbate systemꢀ, the active catalyst
[CuLn]þ, is generated in situ from the copper complex 4 via reduction with ascorbic
acid. Then, activation of the terminal alkyne takes place by insertion of the copper
complex to the terminal alkyne, forming copper(I) acetylide I [28]. Having the
concerted pathways eliminated, we propose that the azide binds to the copper atom via
the N-atom proximal to the C-atom, forming intermediate II. In the next step,
protonolysis of III releases the 1,2,3-triazole IV, thereby completing the catalytic cycle
[12] (Scheme 3, Pathway B).
In conclusion, we developed a safe and efficient protocol for the regioselective
generation of 1-(2-hydroxyalkyl)-1H-1,2,3-triazole derivatives via a three-component
reaction of an oxirane, NaN3, and an alkyne in an environmentally benign solvent, H2O.
By executing several reaction steps in a one-pot reaction and purifying only at the final
stage, this procedure avoids the isolation of the azide intermediate, which significantly
reduced the synthetic process time and improved the overall yield. The process showed
the considerable synthetic advantages in terms of product diversity, mild reaction
condition, simplicity of the reaction procedure, and good to excellent yields.
Furthermore, copper(II) catalyst 4 can be recovered and recycled by simple filtration
of the reaction mixture and reused for at least ten consecutive trials without decrease in
activity.

440
Helvetica Chimica Acta – Vol. 93 (2010)

Helvetica Chimica Acta – Vol. 93 (2010)
441

442
Helvetica Chimica Acta – Vol. 93 (2010)

Helvetica Chimica Acta – Vol. 93 (2010)
443

444
Helvetica Chimica Acta – Vol. 93 (2010)
Table 4. Catalyst-Recyclability Studies on the Synthesis of 1-(2-Hydroxyethyl)-1H-1,2,3-triazole Deriv-
ative 7a from 2-Phenyloxirane (5a; 1 mmol), Phenylacetylene (6a; 1 mmol), NaN3 (1.2 mmol), Ascorbic
Acid (0.2 mmol), and 4 (5 mol-%) in H2O at Room Temperature
Number
of uses
Yielda) [%]
Recovery
of catalyst [%]
Number
of uses
Yielda) [%]
Recovery
of catalyst [%]
1
2
3
4
5
90
90
90
90
89
> 98
> 98
> 98
> 98
97
6
7
8
9
10
89
87
87
87
85
97
95
95
95
94
a) Yield of isolated product.
Experimental Part
General. Chemical materials were either prepared in our laboratories or were purchased from Fluka,
Aldrich, or Merck. The purity determination of the substrates and reaction monitoring were
accomplished by TLC (silica gel PolyGram SILG/UV254 plates). Column chromatography (CC): short
glass columns (Ø 2 – 3 cm) of silica gel 60 (SiO2; 70 – 230 mesh); 15 – 30 g of SiO2 for 1 g of crude mixture.
M.p.: open capillary; Bꢀchi-535 circulating-oil melting-point apparatus. IR Spectra: Shimadzu-FT-IR
8300 spectrophotometer; in cmꢀ1. NMR Spectra: Bruker-Avance-DPX-250 (1H at 250 and 13C at
62.9 MHz) in pure deuterated solvents with Me4Si as internal standard; d in ppm, J in Hz. MS: Shimadzu-
GCMS-QP-1000-EX instruments at 70 or 20 eV; in m/z (rel. %).
1-(2-Hydroxyalkyl)-1H-1,2,3-triazole Derivatives: General Procedure. The [Cu(bhppda)H2O] (4)
[24] catalyst was subjected to ten successive reuses under the following conditions: For each reaction,
oxirane 5 (1 mmol), alkyne 6 (1 mmol), and NaN3 (1.2 mmol) were mixed and stirred in H2O (1 ml) in
the presence of 4 (5 mol-%) and ascorbic acid (10 mol-%) at r.t. in an uncapped vial. After the
completion of the reaction (TLC (hexane/AcOEt 4 :1) monitoring), the mixture was diluted by H2O
(5 ml), then the whole mixture was directly passed through a Celite pad and rinsed with AcOEt (3 ꢁ
10 ml). The combined org. layer was washed with sat. brine, dried (Na2SO4), and concentrated and
the residue recrystallized from EtOH/H2O 3 :1 or purified by CC (SiO2, hexane/AcOEt 4 :1): pure 7.
a,4-Diphenyl-1H-1,2,3-triazole-1-ethanol (7a): Yield 238.5 mg (90%). Colorless solid. M.p. 125.5 –
126.58. IR (KBr): 3398 (br.), 3093m, 2928m, 1458s, 1427m, 1223m, 1118w, 1076s, 1049s, 1030m, 760s,
694s. 1H-NMR (CDCl3): 3.62 (s, 1 H); 4.15 (dd, J ¼ 12.7, 3.8, 1 H); 4.56 (dd, J ¼ 12.4, 8.2, 1 H); 5.60 (dd,
J ¼ 8.2, 3.7, 1 H); 7.17 – 7.26 (m, 5 H); 7.28 (s, 1 H); 7.29 – 7.34 (m, 2 H); 7.62 – 7.69 (m, 3 H). 13C-NMR
(CDCl3): 64.7; 67.3; 120.7; 126.0; 127.2; 128.2; 128.8; 129.0; 130.2; 136.2; 147.4. EI-MS: 267 (0.2, [M þ
2]þ), 266 (2.9, [M þ 1]þ), 265 (6.9, Mþ), 218 (3.7), 206 (43.1), 178 (9.5), 116 (100.0), 77 (40). Anal.
calc. for C16H15N3O (265.31): C 72.43, H 5.70; found: C 72.56, H 5.67.
4-(Phenoxymethyl)-a-phenyl-1H-1,2,3-triazole-1-ethanol (7b): Yield 265.8 mg (90%). Colorless
solid. M.p. 78 – 798. IR (KBr): 3421 (br.), 2870w, 1597m, 1458m, 1223s, 1134w, 1053s, 860m, 756s, 706s.
1H-NMR (CDCl3): 3.25 (s, 1 H); 3.98 (dd, J ¼ 12.3, 3.9, 1 H); 4.36 (dd, J ¼ 12.3, 8.4, 1 H); 4.94 (s, 2 H);
5.44 (dd, J ¼ 8.2, 3.9, 1 H); 6.72 – 6.76 (m, 3 H); 6.99 – 7.16 (m, 7 H); 7.40 (s, 1 H). 13C-NMR (CDCl3):
61.9; 64.2; 65.8; 114.8; 116.2; 121.4; 123.9; 127.6; 128.8; 129.0; 130.1; 136.2; 143.6; 158.0. EI-MS: 297 (1.0,
[M þ 2]þ), 296 (3.2, [M þ 1]þ), 295 (10.6, Mþ), 236 (4.5), 202 (42.3), 174 (23.4), 144 (48.0), 121 (100.0),
103 (84.6), 77 (75.9), 54 (73.2). Anal. calc. for C17H17N3O2 (295.34): C 69.14, H 5.80; found: C 69.17, H
5.82.
4-[(4-Methylphenoxy)methyl]-a-phenyl-1H-1,2,3-triazole-1-ethanol (7c): Yield 265.9 mg (87%).
Colorless solid. M.p. 94 – 958. IR (KBr): 3418 (br.), 2870w, 1608w, 1508s, 1458m, 1292w, 1234s, 1176m,
1007s, 957m, 860m, 822s, 705s, 517m. 1H-NMR (CDCl3): 2.15 (s, 3 H); 4.04 (dd, J ¼ 12.1, 4.0, 1 H); 4.07 (s,
1 H); 4.39 (dd, J ¼ 11.9, 8.4, 1 H); 4.95 (s, 2 H); 5.55 (dd, J ¼ 8.2, 3.8, 1 H); 6.71 (d, J ¼ 8.5, 2 H); 6.93 (d,
J ¼ 8.3, 2 H); 7.08 – 7.21 (m, 5 H); 7.53 (s, 1 H). 13C-NMR (CDCl3): 20.5; 61.9; 64.5; 67.2; 114.7; 123.7;

Helvetica Chimica Acta – Vol. 93 (2010)
445
Scheme 3
125.9; 128.8; 130.0; 130.5; 136.1; 143.9; 156.1. EI-MS: 311 (1.2, [M þ 2]þ), 310 (3.2, [M þ 1]þ), 309 (10.8,
Mþ), 250 (4.2), 202 (23.4), 174 (42.3), 144 (42.4), 121 (100.0), 103 (80.7), 77 (73.9), 54 (88.5). Anal. calc.
for C18H19N3O2 (309.15): C 69.88, H 6.19; found: C 69.86, H 6.16.
4-[(4-Chlorophenoxy)methyl]-a-phenyl-1H-1,2,3-triazole-1-ethanol (7d): Yield 290.1 mg (88%).
Colorless solid. M.p. 83 – 848. IR (KBr): 3105 (br.), 2928w, 2854w, 1716w, 1593w, 1493s, 1250s, 1053s,
1
829m, 748w, 698m. H-NMR (CDCl3): 3.94 (dd, J ¼ 12.1, 4.2, 1 H); 4.28 (dd, J ¼ 12.1, 8.4, 1 H); 4.32 (s,
1 H), 4.83 (s, 2 H); 5.47 (dd, J ¼ 8.3, 4.1, 1 H); 6.62 (dd, J ¼ 6.9, 2.1, 2 H); 6.96 (dd, J ¼ 6.8, 2.2, 2 H);

446
Helvetica Chimica Acta – Vol. 93 (2010)
6.99 – 7.10 (m, 5 H); 7.48 (s, 1 H). 13C-NMR (CDCl3): 61.9; 64.2; 67.4; 116.1; 123.9; 126.0; 127.3; 128.8;
128.9; 129.4; 129.6; 129.9; 136.1; 143.2; 156.8. EI-MS: 331 (0.3, [M þ 2]þ), 330 (0.7, [M þ 1]þ), 329 (1.4,
Mþ), 271 (0.3), 270 (1.1), 209 (1.1), 210 (0.6), 144 (22.0), 121 (37.6), 103 (42), 83 (100.0), 54 (44.4). Anal.
calc. for C17H16ClN3O2 (329.78): C 61.91, H 4.89; found: C 61.90, H, 4.87.
4-[(4-Nitrophenoxy)methyl]-a-phenyl-1H-1,2,3-triazole-1-ethanol (7e): Yield 306.2 mg (90%).
Brown solid. M.p. 108 – 1098. IR (KBr): 3333 (br.), 3151w, 2835w, 1593s, 1504s, 1384s, 1254s, 1176w,
1111s, 1061m, 1003s, 868s, 841s, 752s, 690s. 1H-NMR (CDCl3): 3.62 (s, 1 H); 4.19 (dd, J ¼ 12.2, 3.9, 1 H);
4.56 (dd, J ¼ 12.2, 8.4, 1 H); 5.24 (s, 2 H); 5.68 (dd, J ¼ 8.2, 3.8, 1 H); 7.02 (d, J ¼ 9.2, 2 H); 7.21 – 7.35 (m,
5 H); 7.69 (s, 1 H); 8.15 (d, J ¼ 9.2, 2 H). 13C-NMR (CDCl3): 62.3; 64.7; 67.3; 114.8; 124.0; 125.9; 127.1;
129.1; 129.2; 135.7; 141.8; 142.6; 163.1. EI-MS: 310 (2.4), 281 (2.3), 228 (2.6), 202 (55.9), 156 (31.5), 144
(92.9), 129 (48.5), 121 (100.0), 103 (78.9), 91 (54.6), 77 (39.9), 54 (32.5). Anal. calc. for C17H16N4O4
(340.33): C 59.99, H 4.74; found: C 59.97, H 4.72.
4-[(10H-Phenothiazin-10-yl)methyl]-a-phenyl-1H-1,2,3-triazole-1-ethanol (7f): Yield 312.3 mg
(78%). Colorless solid. M.p. 151 – 1528. IR (KBr): 3418 (br.), 3059w, 2870w, 1589w, 1458s, 1335m,
1284w, 1223m, 1130m, 1053m, 748s, 702m. 1H-NMR (CDCl3): 2.81 (s, 1 H); 4.13 (dd, J ¼ 12.4, 3.8, 1 H);
4.49 (dd, J ¼ 12.4, 8.4, 1 H); 5.20 (s, 2 H); 5.54 (dd, J ¼ 8.2, 3.7, 1 H); 6.74 (d, J ¼ 8.0, 2 H); 6.88 (t, J ¼ 7.4,
2 H); 6.99 – 7.10 (m, 5 H); 7.09 (dd, J ¼ 7.5, 1.5, 2 H); 7.28 (dd, J ¼ 5.4, 1.7, 2 H); 7.29 (s, 1 H). 13C-NMR
(CDCl3): 44.9; 64.9; 67.1; 115.3; 122.8; 123.5; 124.0; 126.7; 127.2; 128.8; 128.9; 136.0; 144.2; 144.9. EI-MS:
402 (0.7, [M þ 2]þ), 401 (6.0, [M þ 1]þ), 400 (13.1, Mþ), 280 (1.1), 236 (8.5), 198 (100.0), 121 (14.5), 103
(17.9), 83 (29.1), 55 (55.4). Anal. calc. for C23H20N4OS (400.50): C 68.98, H 5.03; found: C 68.96, H 5.05.
2,2’-{{{[1-(2-Hydroxy-2-phenylethyl)-1H-1,2,3-triazol-4-yl]methyl}imino}diethane-2,1-diyl}bis[1H-
isoindole-1,3(2H)-dione] (7g): Yield 485.4 mg (86%). Oil. IR (neat): 3464 (br.), 2847w, 1770s, 1709vs,
1
1400s, 1219w, 1049w, 756s, 717s. H-NMR (CDCl3): 2.67 – 2.77 (m, 4 H); 3.59 – 3.65 (m, 4 H); 3.70 (s,
1 H); 3.80 (s, 2 H); 4.07 (dd, J ¼ 12.3, 3.8, 1 H); 4.45 (dd, J ¼ 12.3, 8.4, 1 H); 5.49 (dd, J ¼ 8.4, 3.7, 1 H);
7.11 – 7.26 (m, 5 H); 7.35 (s, 1 H); 7.54 – 7.57 (m, 8 H). 13C-NMR (CDCl3): 31.8; 47.8; 51.2; 64.8; 66.9;
122.9; 123.4; 125.9; 127.9; 128.5; 128.8; 131.8; 133.7; 136.4; 143.6; 168.1. Anal. calc. for C31H28N6O5
(564.591): C 65.95, H 5.00; found: C 65.75, H 4.98.
1-Chloro-4-{[1-(2-hydroxy-2-phenylethyl)-1H-1,2,3-triazol-4-yl]methoxy}-9H-thioxanthen-9-one
(7h): Yield 403.9 mg (87%). Yellow solid. M.p. 102 – 1038. IR (KBr): 3387 (br.), 2920w, 1643s, 1578m,
1431s, 1296s, 1250s, 1045s, 748s. 1H-NMR (CDCl3): 3.75 (s, 1 H); 4.11 – 4.15 (m, 1 H); 4.47 – 4.55 (m, 1 H);
5.18 (s, 2 H); 5.53 (dd, J ¼ 7.7, 3.2, 1 H); 6.99 (d, J ¼ 8.7, 1 H); 7.14 – 7.30 (m, 7 H); 7.39 (t, J ¼ 7.7, 2 H ) ; 7.69
(s, 1 H); 8.21 (d, J ¼ 8.5, 1 H). 13C-NMR (CDCl3): 62.4; 63.7; 66.3; 112.7; 123.2; 124.7; 125.2; 125.5; 126.1;
126.8; 127.8; 128.0; 128.2; 129.4; 130.9; 134.1; 134.9; 150.3; 178.8. EI-MS: 423 (0.1), 389 (0.1), 366 (0.1),
346 (0.2), 312 (0.1), 295 (16.7), 222 (8.6), 193 (17.5), 167 (16.2), 149 (73.6), 117 (69.5), 77 (100), 57
(53.6). Anal. calc. for C24H18ClN3O3S (463.937): C 62.13, H 3.91; found: C 61.98, H 4.06.
2-{[1-(2-Hydroxy-2-phenylethyl)-1H-1,2,3-triazol-4-yl]methoxy}-9H-thioxanthen-9-one (7i): Yield
347.8 mg (81%). Yellow solid. M.p. 161 – 1628. IR (KBr): 3433s, 3132w, 2920w, 1624s, 1589s, 1473m,
1338m, 1215m, 1119w, 1007w, 744m. 1H-NMR (CDCl3): 3.75 (s, 1 H); 4.07 – 4.23 (m, 1 H); 4.52 (dd, J ¼
12.4, 2.8, 1 H); 5.22 (s, 2 H); 5.58 (dd, J ¼ 8.2, 3.8, 1 H); 7.14 – 7.64 (m, 11 H); 8.21 (d, J ¼ 2.8, 1 H); 8.53
(dd, J ¼ 8.6, 0.8, 1 H). 13C-NMR (CDCl3): 62.0; 64.9; 67.3; 111.6; 122.7; 125.9; 126.1; 127.2; 127.4; 128.7;
129.1; 132.0; 135.9; 137.4; 156.8; 179.4. EI-MS: 431 (3.7, [M þ 2]þ), 430 (10.6, [M þ 1]þ), 429 (23.0, Mþ),
404 (1.3), 370 (3.5), 342 (1.4), 309 (1.7), 281 (3.1), 265 (9.0), 228 (100), 200 (27.6), 174 (1.3), 144 (23.8),
121 (44.6), 103 (36.7), 77 (23.6), 54 (41.9). Anal. calc. for C24H19N3O3S (429.492): C 67.12, H 4.46; found:
C 66.93, H 4.66.
4-{[(5-Chloroquinolin-8-yl)oxy]methyl}-a-phenyl-1H-1,2,3-triazole-1-ethanol (7j): Yield 331.2 mg
(87%). Colorless solid. M.p. 170 – 1728. IR (KBr): 3310 (br.), 31248m, 2943s, 2862w, 1439s, 1238s, 1088s,
1057s, 980w, 771s, 698s. 1H-NMR (CDCl3): 3.24 (s, 1 H); 4.13 – 4.16 (m, 1 H); 4.43 – 4.52 (m, 1 H); 5.43 (s,
2 H); 5.53 (dd, J ¼ 8.2, 3.9, 1 H); 7.08 – 7.30 (m, 5 H); 7.42 – 7.48 (m, 3 H); 7.64 (s, 1 H); 8.45 (dd, J ¼ 8.6,
1.6, 1 H); 8.84 (d, J ¼ 2.8, 1 H). 13C-NMR (CDCl3): 62.9; 64.9; 67.3; 109.9; 122.3; 124.3; 126.4; 127.2;
129.1; 133.1; 135.8; 140.6; 143.5; 149.7. EI-MS: 382 (2.8, [M þ 2]þ), 381 (2.1, [M þ 1]þ), 380 (6.7, Mþ), 321
(6.2), 231 (8.5), 189 (8.1), 179 (100), 151 (22.1), 121 (34.0), 103 (36.7), 54 (42.3). Anal. calc. for
C20H17ClN4O2 (380.832): C 63.08, H 4.50; found: C 62.89, H 4.67.

Helvetica Chimica Acta – Vol. 93 (2010)
447
4-(Hydroxymethyl)-a-phenyl-1H-1,2,3-triazole-1-ethanol (7k): Yield 180.5 mg (85%). Colorless
solid. M.p. 110 – 1118. IR (KBr): 3340 (br.), 3167s, 2932w, 2893w, 1454s, 1234m, 1119s, 1084s, 1011s, 849m,
795m, 702s. 1H-NMR (CDCl3): 4.03 (dd, J ¼ 12.3, 3.6, 1 H); 4.33 – 4.46 (m, 3 H); 4.52 (s, 2 H); 5.58 (dd,
J ¼ 8.8, 3.8, 1 H); 7.13 – 7.30 (m, 5 H); 7.52 (s, 1 H). 13C-NMR (CDCl3): 53.1; 64.5; 67.1; 122.9; 125.9; 127.1;
128.9; 136.0; 147.3. Anal. calc. for C11H13N3O2 (219.240): C 60.26, H 5.98; found: C 60.22, H 6.04.
4-(1-Hydroxy-1-methylethyl)-a-phenyl-1H-1,2,3-triazole-1-ethanol (7l): Yield 197.7 mg (80%). Col-
orless solid. M.p. 119.5 – 120.58. IR (KBr): 3356 (br.), 3128m, 2970m, 1458w, 1358w, 1165s, 1076s, 957m,
860m, 721m, 698m. 1H-NMR (CDCl3): 1.53 (s, 6 H); 2.99 (s, 2 H); 4.09 (dd, J ¼ 12.7, 3.7, 1 H); 4.50 (dd,
J ¼ 12.3, 8.4, 1 H); 5.54 (dd, J ¼ 8.3, 3.6, 1 H); 7.15 – 7.31 (m, 5 H); 7.43 (s, 1 H). 13C-NMR (CDCl3): 30.1;
64.7; 67.2; 68.2; 120.3; 127.2; 128.9; 136.1; 155.2. EI-MS: 247 (0.8, Mþ), 246 (3.3), 232 (36.8), 216 (20.8),
188 (28.7), 170 (41.3), 149 (14.2), 130 (42.5), 103 (100.0), 84 (70.7), 55 (47.8). Anal. calc. for C13H17N3O2
(247.293): C 63.14, H 6.93; found: C 63.09, H 6.98.
4-Butyl-a-phenyl-1H-1,2,3-triazole-1-ethanol (7m): Yield 196.2 mg (80%). Oil. IR (neat): 3302 (br.),
3093m, 2932m, 1551w, 1454s, 1229m, 1072m, 756m, 702s. 1H-NMR (CDCl3): 0.89 (t, J ¼ 7.3, 3 H); 1.24 –
1.41 (m, 2 H); 1.53 – 1.65 (m, 2 H); 2.65 (t, J ¼ 7.5, 2 H); 3.73 (s, 1 H); 4.15 (dd, J ¼ 12.3, 3.9, 1 H); 4.53
(dd, J ¼ 12.3, 8.4, 1 H); 5.60 (dd, J ¼ 8.2, 3.8, 1 H); 7.18 – 7.37 (m, 6 H). 13C-NMR (CDCl3): 13.8; 22.3;
25.1; 31.3; 64.7; 68.1; 121.5; 127.6; 128.6; 128.8; 136.5; 148.1. Anal. calc. for C14H19N3O (245.320): C 68.54,
H 7.81; found: C 68.44, H 7.69.
5,6,7,8,9,10-Hexahydro-7-{[1-(2-hydroxy-2-phenylethyl)-1H-1,2,3-triazol-4-yl]methyl}-2H-1,13,4,7,
10-benzodioxatriazacyclopentadecine-3,11(4H,12H)-dione (7n): Yield 390.6 mg (79%). Colorless solid.
M.p. 105 – 1068. IR (KBr): 3398s, 2932w, 2854w, 1682vs, 1535s, 1504s, 1439w, 1257s, 1219w, 1126m, 1053m,
756m. 1H-NMR (CDCl3): 2.77 (t, J ¼ 5.3, 4 H); 3.48 (t, J ¼ 5.3, 4 H); 3.77 (s, 2 H); 4.07 (dd, J ¼ 12.3, 3.9,
1 H); 4.36 (s, 4 H); 4.44 (dd, J ¼ 12.3, 8.5, 1 H); 4.50 (s, 1 H); 5.54 (dd, J ¼ 8.3, 3.8, 1 H); 6.81 – 7.01 (m,
4 H); 7.08 – 7.11 (m, 2 H); 7.26 – 7.29 (m, 3 H); 7.49 (s, 1 H); 7.59 (s, 2 H). 13C-NMR (CDCl3): 35.5; 44.9;
52.4; 64.7; 67.1; 112.9; 122.2; 123.1; 125.8; 126.9; 128.8; 129.1; 136.1; 143.5; 146.3; 167.5. EI-MS: 496 (1.2,
[M þ 2]þ), 495 (3.2, [M þ 1]þ), 494 (16.0, Mþ), 422 (2.5), 408 (3.6), 373 (2.5), 314 (1.9), 293 (11.4), 292
(29.5), 245 (11.9), 228 (11.5), 203 (12.9), 167 (12.9), 137 (28.4), 121 (59.3), 103 (45.3), 83 (100.0), 56
(99.8). Anal. calc. for C25H30N6O5 (494.543): C 60.72, H 6.11; found: C 60.89, H 6.08.
1,8-Bis{[1-(2-hydroxy-2-phenylethyl)-1H-1,2,3-triazol-4-yl]methoxy}anthracene-9,10-dione (7o):
Yield 530.9 mg (85%). Yellow solid. M.p. 167 – 1688. IR (KBr): 3394 (br.), 2932w, 2878w, 2338w,
1670vs, 1585s, 1454m, 1315m, 1277m, 1242s, 1053m, 980m, 744m, 702w. 1H-NMR (CDCl3): 4.10 (dd, J ¼
12.3, 3.8, 2 H); 4.15 (s, 1 H); 4.45 – 4.56 (m, 3 H); 5.18 (s, 4 H); 5.66 – 5.71 (m, 2 H); 7.13 – 7.23 (m, 6 H);
7.30 – 7.35 (m, 4 H); 7.44 (t, J ¼ 8.2, 2 H); 7.47 (s, 2 H); 7.69 (d, J ¼ 7.6, 2 H); 7.90 (d, J ¼ 6.8, 2 H).
13C-NMR (CDCl3): 63.9; 64.6; 67.2; 119.9; 120.6; 124.3; 127.1; 128.7; 128.9; 134.0; 134.6; 136.1; 143.4;
157.8; 183.2. Anal. calc. for C36H30N6O6 (642.660): C 67.28, H 4.71; found: C 67.42, H 4.87.
a-(Phenoxymethyl)-4-phenyl-1H-1,2,3-triazole-1-ethanol (7p): Yield 230.3 mg (78%). Colorless
solid. M.p. 125 – 1268. IR (KBr): 3425 (br.), 3074w, 2920w, 1724w, 1597m, 1493w, 1250s, 1119w, 1080m,
1
1041m, 752s, 690s. H-NMR (CDCl3): 3.88 (s, 1 H); 4.01 – 4.05 (m, 2 H); 4.55 (dd, J ¼ 12.7, 3.5, 2 H);
4.68 – 4.77 (m, 1 H); 6.90 – 7.02 (m, 3 H); 7.6 – 7.02 (m, 5 H); 7.69 – 7.72 (m, 2 H); 7.85 (s, 1 H). 13C-NMR
(CDCl3): 53.5; 68.6; 68.9; 114.5; 121.4; 121.6; 125.5; 128.1; 128.8; 129.6; 130.0; 147.2; 158.2. EI-MS: 297
(1.6, [M þ 2]þ), 296 (4.4, [M þ 1]þ), 295 (7.1, Mþ), 279 (7.3), 243 (3.7), 222 (5.1), 202 (9.0), 167 (22.1),
149 (62.5), 117 (35.7), 94 (24.2), 77 (51.8), 57 (100.0). Anal. calc. for C17H17N3O2 (295.336): C 69.14, H
5.80; found: C 68.98, H 5.93.
4-Phenyl-a-[(prop-2-en-1-yloxy)methyl]-1H-1,2,3-triazole-1-ethanol (7q): Yield 236.2 mg (80%).
Colorless solid. M.p. 71.5 – 728. IR (KBr): 3356 (br.), 3128m, 2970m, 1458w, 1358w, 1165s, 1076s, 957m,
860m, 721m, 698m. 1H-NMR (CDCl3): 3.19 (d, J ¼ 5.0, 2 H); 3.70 (d, J ¼ 5.4, 2 H); 3.96 – 4.11 (m, 2 H);
4.27 (dd, J ¼ 13.2, 2.6, 1 H); 4.51 (s, 1 H); 4.93 (dd, J ¼ 17.2, 10.3, 1 H); 4.99 – 5.01 (m, 1 H); 5.53 – 5.64 (m,
1 H); 6.94 – 7.06 (m, 3 H); 7.36 (dd, J ¼ 8.2, 1.7, 2 H); 7.58 (s, 1 H). 13C-NMR (CDCl3): 53.5; 68.9; 71.3;
72.3; 117.4; 121.0; 125.4; 128.0; 128.7; 129.7; 134.2; 147.0. EI-MS: 260 (5.4, [M þ 1]þ), 259 (10.5, Mþ), 230
(4.8), 203 (11.1), 158 (14.9), 132 (16.0), 116 (100.0), 93 (4.2), 77 (46.2), 57 (37.7). Anal. calc. for
C14H17N3O2 (295.304): C 64.85, H 6.61; found: C 64.97, H 6.49.
rel-(1R,2R)-2-(4-Phenyl-1H-1,2,3-triazol-1-yl)cyclohexanol (7r): Yield 201.9 mg (83%). Colorless
solid. M.p. 179 – 1808. IR (KBr): 3310 (br.), 3124m, 2943s, 2862w, 1439s, 1238s, 1088s, 1057s, 980w, 771s,

448
Helvetica Chimica Acta – Vol. 93 (2010)
698s. 1H-NMR (CDCl3): 1.39 – 2.25 (m, 8 H); 4.09 – 4.17 (m, 3 H); 7.23 – 7.36 (m, 3 H); 7.36 (dd, J ¼ 8.2,
1.7, 2 H); 7.69 (s, 1 H). 13C-NMR (CDCl3): 24.1; 24.8; 31.5; 33.8; 67.4; 72.5; 120.1; 125.4; 127.9; 128.7;
130.2. EI-MS: 245 (0.3, [M þ 2]þ), 244 (2.6, [M þ 1]þ), 243 (6.7, Mþ), 215 (1.5), 203 (2.6), 174 (1.7), 158
(3.7), 117 (100.0), 81 (55.7), 55 (23.5). Anal. calc. for C14H17N3O (243.307): C 69.11, H 7.04; found: C
69.03, H 6.89.
rel-(1R,2R)-2-{4-[(4-Nitrophenoxy)methyl]-1H-1,2,3-triazol-1-yl}cyclohexanol (7s): Yield 264.1 mg
(83%). Brown solid. M.p. 143.5 – 1448. IR (KBr): 3394 (br.), 2951w, 2878w, 1589s, 1512s, 1493s, 1458w,
1338s, 1296m, 1254s, 1223m, 1169m, 1111m, 984m, 864m, 837m, 748w. 1H-NMR (CDCl3): 1.34 – 1.49 (m,
3 H); 1.84 – 1.94 (m, 3 H); 2.15 – 2.20 (m, 2 H); 3.09 (s, 1 H); 3.92 – 4.02 (m, 1 H); 4.12 – 4.22 (m, 1 H);
5.22 (s, 2 H); 7.03 (dd, J ¼ 7.2, 2.1, 2 H); 7.73 (s, 1 H); 8.16 (dd, J ¼ 7.2, 2.1, 2 H). 13C-NMR (CDCl3): 23.9;
24.7; 31.7; 34.0; 62.4; 67.0; 72.5; 114.8; 123.2; 125.9; 141.8; 163.1. EI-MS: 320 (0.4, [M þ 2]þ) 319 (0.5,
[M þ 1]þ), 180 (27.2), 152 (79.4), 108 (17.5), 81 (100.0), 56 (55.5). Anal. calc. for C15H18N4O4 (318.33): C
56.60, H 5.70, N 17.60; found: C 56.62, H 5.71, N 17.58.
REFERENCES
[1] R. Huisgen, in ꢃ1,3-Dipolar Cycloaddition Chemistryꢀ, Ed. A. Padwa, J. Wiley & Sons, New York,
1984, Vol. 1, pp. 1 – 176.
[2] Q. Wang, T. R. Chan, R. Hilgraf, V. V. Fokin, K. B. Sharpless, M. G. Finn, J. Am. Chem. Soc. 2003,
125, 3192.
[3] A. J. Link, M. K. S. Vink, D. A. Tirrell, J. Am. Chem. Soc. 2004, 126, 10598.
[4] A. E. Speers, B. F. Cravatt, Chem. Biol. 2004, 11, 535.
[5] T. R. Chan, R. Hilgraf, K. B. Sharpless, V. V. Fokin, Org. Lett. 2004, 6, 2853.
[6] D. D. Dꢄaz, S. Punna, P. Holzer, A. K. McPherson, K. B. Sharpless, V. V. Fokin, M. G. Finn, J. Polym.
Sci., Part A: Polym. Chem. 2004, 42, 4392.
[7] A. J. Scheel, H. Komber, B. I. Voit, Macromol. Rapid Commun. 2004, 25, 1175.
´
[8] P. Wu, A. K. Feldman, A. K. Nugent, C. J. Hawker, A. Scheel, B. Voit, J. Pyun, J. M. J. Frechet, K. B.
Sharpless, V. V. Fokin, Angew. Chem., Int. Ed. 2004, 43, 3928.
[9] W. S. Horne, M. K. Yadav, C. D. Stout, M. R. Ghadiri, J. Am. Chem. Soc. 2004, 126, 15366.
´
[10] C. W. Tornøe, C. Christensen, M. Meldal, J. Org. Chem. 2002, 67, 3057; F. Perez-Balderas, M. Ortega-
´
Mun˜oz, J. Morales-Sanfrutos, F. Hernandez-Mateo, F. G. Calvo-Flores, J. A. Calvo-Asꢄn, J. Isac-
´
Garcꢄa, F. Santoyo-Gonzalez, Org. Lett. 2003, 5, 1951; J. Meng, V. V. Fokin, M. G. Finn, Tetrahedron
Lett. 2005, 46, 4543; B. Gerard, J. Ryan, A. B. Beeler, J. A. Porco Jr., Tetrahedron 2006, 62, 6405; J.
´
Broggi, S. Dꢄez-Gonzalez, J. L. Petersen, S. Berteina-Raboin, S. P. Nolan, L. A. Agrofoglio, Synthesis
2008, 141; A. Marra, A. Vecchi, C. Chiappe, B. Melai, A. Dondoni, J. Org. Chem. 2008, 73, 2458.
[11] V. V. Rostovtsev, L. G. Green, V. V. Fokin, K. B. Sharpless, Angew. Chem., Int. Ed. 2002, 41, 2596.
[12] F. Himo, T. Lovell, R. Hilgraf, V. V. Rostovtsev, L. Noodleman, K. B. Sharpless, V. V. Fokin, J. Am.
Chem. Soc. 2005, 127, 210.
[13] S. Quader, S. E. Boyd, I. D. Jenkins, T. A. Houston, J. Org. Chem. 2007, 72, 1962.
[14] N. Mizuno, M. Misono, Chem. Rev. 1998, 98, 199; G. Sartori, R. Ballini, F. Bigi, G. Bosica, R. Maggi,
P. Righi, Chem. Rev. 2004, 104, 199; M. Wang, P. Li, L. Wang, Eur. J. Org. Chem. 2008, 2255.
[15] B. Lipshutz, B. R. Taft, Angew. Chem., Int. Ed. 2006, 45, 8235.
`
[16] C. Girard, E. ꢅnen, M. Aufort, S.Beauviere, E. Samson, J. Herscovici, Org. Lett. 2006, 8,
1689.
[17] S. Chassaing, M. Kumarraja, A. S. S. Sido, P. Pale, J. Sommer, Org. Lett. 2007, 9, 883.
[18] T. Miao, L. Wang, Synthesis 2008, 363.
[19] I. S. Park, M. S. Kwon, Y. Kim, J. S. Lee, J. Park, Org. Lett. 2008, 10, 497.
[20] E. Saxon, C. R. Bertozzi, Science (Washington, DC, U.S.) 2000, 287, 2007.
´
[21] V. D. Bock, H. Hiemstra, J. H. van Maarseveen, Eur. J. Org. Chem. 2006, 51; S. Dꢄez-Gonzalez, A.
Correa, L. Cavallo, S. P. Nolan, Chem.–Eur. J. 2006, 12, 7558; P. Appukkuttan, W. Dehaen, V. V.
Fokin, E. Van der Eycken, Org. Lett. 2004, 6, 4223; K. Kacprzak, Synlett 2005, 943; Y.-B. Zhao, Z.-Y.
Yan, Y.-M. Liang, Tetrahedron Lett. 2006, 47, 1545.

Helvetica Chimica Acta – Vol. 93 (2010)
449
[22] A. Brik, J. Alexandratos, Y.-C. Lin, J. H. Elder, A. J. Olson, A. Wlodawer, D. S. Goodsell, C.-H.
Wong, ChemBioChem 2005, 6, 1167.
[23] H. Sharghi, M. H. Beyzavi, M. M. Doroodmand, Eur. J. Org. Chem. 2008, 4126; H. Sharghi, M.
Aberi, M. M. Doroodmand, Adv. Synth. Catal. 2008, 350, 2380; H. Sharghi, R. Khalifeh, M. M.
Doroodmand, Adv. Synth. Catal. 2009, 351, 207.
[24] H. Sharghi, M. Hosseini-Sarvari, F. Moeini, Can. J. Chem. 2008, 86, 1044.
[25] K. R. Reddy, C. U. Maheswari, K. Rajgopal, M. L. Kantam, Synth. Commun. 2008, 38, 2158.
[26] J. S. Yadav, B. V. S. Reddy, B. Jyothirmai, M. S. R. Murty, Tetrahedron Lett. 2005, 46, 6559.
[27] H. Sharghi, A. R. Hassani Nejad, M. A. Nasseri, New J. Chem. 2004, 28, 946.
[28] M. Kinugasa, S. Hashimoto, J. Chem. Soc., Chem. Commun. 1972, 466; M. Miura, M. Enna, K.
Okuro, M. Nomura, J. Org. Chem. 1995, 60, 4999; M. M.-C. Lo, G. C. Fu, J. Am. Chem. Soc. 2002,
124, 4572.
Received June 9, 2009