Copper-mediated trifluoromethylation of 5-iodotriazole with (trifluoromethyl)trimethylsilane promoted by silver carbonate

Article abstract of DOI:10.1016/j.jfluchem.2013.10.006

A novel and mild method for copper-mediated trifluoromethylation of 5-iodotriazole using (trifluoromethyl)trimethylsilane (Me₃SiCF ₃) as trifluoromethylating reagent with the assistance of Ag ₂CO₃ was developed.

Full text of DOI:10.1016/j.jfluchem.2013.10.006

Accepted Manuscript
Title: Copper-mediated trifluoromethylation of 5-iodotriazole
with (trifluoromethyl)trimethylsilane promoted by silver
carbonate
Author: Dan Fu Jian Zhang Song Cao
PII:
S0022-1139(13)00333-3
DOI:
Reference:
http://dx.doi.org/doi:10.1016/j.jfluchem.2013.10.006
FLUOR 8208
To appear in:
FLUOR
Received date:
Revised date:
Accepted date:
12-9-2013
1-10-2013
5-10-2013
Please cite this article as: D. Fu, J. Zhang, S. Cao, Copper-mediated
trifluoromethylation of 5-iodotriazole with (trifluoromethyl)trimethylsilane
promoted by silver carbonate, Journal of Fluorine Chemistry (2013),
http://dx.doi.org/10.1016/j.jfluchem.2013.10.006
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Graphical abstract
Copper-mediated trifluoromethylation of 5-iodotriazole with
(trifluoromethyl)trimethylsilane promAogteCdOby silver carbonate
2
3
Dan Fua, Jian Zhang a, and Song Cao a, b *
N
N
a
R1
N
1
N
Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and
N
R
N
CuI / KF / phen / DMF
+
Me3SiCF3
R2
°
2
Technology, Shanghai 200237, China
air, 100 C
R
F3C
I
b Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences,
Shanghai 200032, China
A
novel and mild method for copper-mediated trifluoromethylation of 5-iodotriazole using
(trifluoromethyl)trimethylsilane as trifluoromethylating reagent with the assistance of Ag2CO3 was developed.
N
N
R1
N
R1
N
N
N
CuI / KF / phen / Ag2CO3 / DMF
100 °C
+
Me3SiCF3
R2
R2
F3C
I
1
Page 1 of 22

Copper-mediated
trifluoromethylation
of
5-iodotriazole
with
(trifluoromethyl)trimethylsilane promoted by silver carbonate
Dan Fu a, Jian Zhang a, and Song Cao a, b *
a Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of
Science and Technology, Shanghai 200237, China
b Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese
Academy of Sciences, Shanghai 200032, China
*Corresponding author. Tel: +86-21-64253452; fax: +86-21-64252603
E-mail address: scao@ecust.edu.cn
2
Page 2 of 22

Copper-mediated trifluoromethylation of 5-iodotriazole with
(trifluoromethyl)trimethylsilane promoted by silver carbonate
Dan Fu a, Jian Zhang a, and Song Cao a, b
*
a Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of
Science and Technology, Shanghai 200237, China
b Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese
Academy of Sciences, Shanghai 200032, China
Tel: +86-21-64252945; fax: +86-21-64252603
E-mail : scao@ecust.edu.cn
Abstract: A novel and mild method for copper-mediated trifluoromethylation of 5-iodotriazole
using (trifluoromethyl)trimethylsilane (Me3SiCF3) as trifluoromethylating reagent with the
assistance of Ag2CO3 was developed.
Keywords: 5-Iodotriazole, Trifluoromethylation, (Trifluoromethyl)trimethylsilane, Silver
carbonate
1. Introduction
Compounds containing trifluoromethyl groups have received considerable attention due to their
important applications in the pharmaceutical, agrochemical and polymer industry [1]. Up to now,
various methods have been developed for trifluoromethylation of diverse molecules such as arenes
[2], aryl halides [3], carbonyl compounds [4], arylboronic acids [5] and terminal alkynes [6].
However, the incorporation of the trifluoromethyl group into heteroarenes still remains a great
challenge for the chemical community [7].
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1,2,3-Triazoles derivatives have occupied a unique position in heterocyclic chemistry due to
their wide range of biological activities [8]. However, the method of the introduction of
trifluoromethyl group to triazole ring is very scarce [9]. For example, Bakulev reported the
regioselective
synthesis
of
5-trifluoromethyl-1,2,3-triazoles
via
cyclization
of
1-trifluoromethyl-1,3-dicarbonyl compounds with azides [10]. In 2011, Wang et al. synthesized
two trifluoromethyl-containing 1,4,5-trisubstituted 1,2,3-triazoles by treatment of phenyl azide
with ethyl 4,4,4-trifluoroacetoacetate and 4,4,4-trifluoro-1-phenylbutane-1,3-dione in presence of
organocatalytic acyclic diethyl amine [11]. More recently, we reported a facile and practical
method for the synthesis of CF3-containing 1-aryl-1,4,5-trisubstituted 1,2,3-triazole derivatives via
a one-pot three-component reaction of boronic acids, sodium azide, and active methylene ketones,
such as ethyl 4,4-difluoroacetoacetate or ethyl 4,4,4-trifluoroacetoacetate in the presence of
Cu(OAc)2 and piperidine [12]. To the best of our knowledge, up to now, there is no report on the
direct trifluoromethylation of triazole ring with trifluoromethylating reagent. In continuation of our
interest in the synthesis of novel functionalized 1,2,3- triazoles [13], in this paper, we report
Cu-mediated trifluoromethylation of 5-iodotriazole by the combination of Me3SiCF3/CuI/KF/phen
(1,10-phenanthroline) using Ag2CO3 as a promoter (Scheme 1).
Here insert Scheme 1
2. Results and discussion
5-Iodo-1,4-disubstituted triazoles are versatile synthetic intermediates and can be used for the
further construction of diverse 1,4,5-trisubstituted-1,2,3-triazoles [14]. However, a practical
drawback of this building block is that the carbon iodine bond in this triazole ring is easily cleaved
and undergo reductive dehalogenation in the presence of copper salt, and can generate the
corresponding 5-prototriazole in considerable yields during the course of preparation and
functionalization of 5-iodotriazoles [15]. Therefore, an intricate synthetic challenge of
trifluoromethylation of 5-iodotriazoles is to inhibit this side reaction (protodehalogenation).
Generally, the most important method for trifluoromethylation of aryl iodides involves the use
of Me3SiCF3 as trifluoromethylating reagent in presence of a stoichiometric amount of CuI and KF
4
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[16a] or a catalytic amount of CuI and KF along with 10 mol% phen [16b]. Thus, we chose the
coupling of 1-benzyl-5- iodo-4-phenyl-1H-1,2,3-triazole 5a with Me3SiCF3 in presence of copper
salt, KF and phen as a model reaction to determine the optimal reaction conditions (Table 1).
Initially, we investigated the influence of solvent on the reaction (entries 1-6). The choice of
solvents proved crucial for the formation of trifluoromethylated product 6a. When toluene, CH3CN
were used as solvents, no desired product 6a was observed and gave a significant amount of
5-prototriazole 6a′ along with the recovered starting material 5a. Running the reaction in THF only
afforded 5-prototriazole 6a′ as the exclusive product. Fortunately, when the reaction was carried
out in CH3NO2, DMSO or DMF, the trifluoromethylation took place and generated the mixture of
trifluoromethylated product 6a and 5-prototriazole 6a′ (entries 4-6). The aprotic polar solvent,
DMF, proved to be a more suitable solvent for this transformation and could afford 6a in 68% yield.
However, the yield is unsatisfactory. Therefore, it was necessary to optimize the reaction conditions
or develop a practical method for the trifluoromethylation of 5-iodotriazole.
Here insert Table 1
Attempts to improve the yield of 6a by using other trifluoromethylating reagents were
unsuccessful. No product was observed and large amounts of starting material 5a were recovered
when we employed sodium trifluoromethanesulfinate (CF3SO2Na, Langlois reagent) as the
trifluoromethyl source in the presence of tert-butylhydroperoxide (TBHP) [17].
Trifluoromethylation of 5a with Togni reagent or Umemoto reagent in the presence of Cu catalyst
afforded the mixture of 6a and 6a′ [18]. The yield of 6a was around 55%.
Next, we turned our efforts to improve the yield of trifluoromethylated product 6a using
Me3SiCF3/CuI/KF/DMF system. According to literatures, oxidants exhibit a strong effect on the
copper-mediated or catalyzed oxidative trifluoromethylation of terminal alkynes [19], aryl boronic
acids [20] indoles [21] and heteroarenes [22] with Me3SiCF3. However, it is reported that
trifluoromethylation of aryl iodides with Me3SiCF3 could proceed smoothly in absence of oxidant
[23]. Considering that the carbon-iodine bond of the triazole easily undergoes reductive
dehalogenation, we envisaged that the competing protodehalogenation reaction might be
5
Page 5 of 22

suppressed by addition of some oxidants to the reaction system. Thus, firstly, reaction of
5-iodo-1,2,3-triazole 5a with Me3SiCF3 was carried out under argon or oxygen atmosphere (Table 1,
entries 7 and 8). The results indicated that there are no apparent differences in the yields of 6a when
the reactions were performed under ambient atmosphere of air, argon and oxygen. To improve the
transformation, other oxidants such as K2S2O8, DDQ, Cu(OAc)2 and 1,4-benzoquinone were
further tested (entries 9-12). When 2,3-dichlorobutane was applied as oxidant, the yield of the
desired product 6a increased to 80% and the side product decreased to 20% (entry 13). Much to our
delight, the trifluoromethylation of 5-iodo-1,2,3-triazole 5a with Me3SiCF3 using Ag2CO3 as
oxidant proceeds very efficiently and afforded trifluoromethylated product 6a in almost
quantitative yields and no 5-prototriazole 6a′ was observed (entries 14-17). However, at least two
equivalent amount of Ag2CO3 had to be used to ensure the transformation in near quantitative yield.
The amount of Ag2CO3 could be lowered to 1.5 equivalents, while the efficiency of the conversion
was slightly decreased (entry 18). The use of other silver salts such as CH3CO2Ag or AgNO3 gave
the mixture of 6a′ and 5a, no 6a was detected (entries 19 and 20).
The effect of amount of CuI on the reaction was also studied. Decreasing the amount of the CuI
to less than 1 equivalent per equivalent of 5a gave trifluoromethylated product 6a in poor yields
(entries 21 and 22). Using copper or other Cu salts, such as CuCl and Cu(OAc)2 instead of CuI
significantly decreased the yield of 6a (entries 23-25), whereas CuBr still afforded the expected
product in high yield (entry 26). It should be mentioned that in the absence of phen, no desired
product was observed and gave a mixture of 6a′ and 5a in a 61:30 ratio.
With the optimized reaction conditions in hand (Table 1, entry 17) we next examined the scope
and limitations of the Cu-mediated trifluoromethylation of 5-iodotriazole using
Me3SiCF3/CuI/KF/phen/Ag2CO3 system. As shown in Table 2, the trifluoromethylation of all the
substrates proceeded smoothly to give the corresponding products in 52-90% isolated yields. In
general, the properties of the substituents at 5-position of the triazole ring (R2 group) had little
influence on the formation of 6a-t, however the substituents attached to the triazole nitrogen atom
(R1 group) had an obvious influence on the yields of reaction. Substrate with electron-donating
group such as methyl on the benzene ring which is adjacent to methylene (CH2-N) afforded the
trifluoromethylated products in excellent yield (6l), whereas the electron-withdrawing groups on
the benzene ring such as CN, Cl were unfavorable for the reaction, and afforded the expected
6
Page 6 of 22

products in relatively low yields (6m, 6n). Replacement of the benzene ring in the R1 group with
the heterocyclic rings such as furan, thiazole and pyridine often resulted in diminished product
yields (6o-t). The presence of the methylene group which is adjacent to the nitrogen in the triazole
ring is necessary for this transformation.
Here insert Table 2
Based on the above observations, we suggest that the mechanism is analogous to those
proposed in the literatures [16b, 24]. The formation of the key reactive species, (Phen)CuCF3
generated in situ from Me3SiCF3, is essential for efficient conversion. The silver carbonate might
have cooperative effects on the Cu-mediated trifluoromethylation of 5-iodotriazoles [25]. It is
reported that different silver salts have different effects on trifluoromethylation reaction [26].
However, in our case, the effect of silver carbonate is obviously different from the literatures. The
silver carbonate plays another important role in inhibiting side reaction (protodehalogenation).
3. Conclusions
In conclusion, we have developed a novel and efficient copper-mediated protocol for the
trifluoromethylation of 5-iodotriazole using Me3SiCF3 as trifluoromethylating reagent with the
assistance of Ag2CO3. A variety of functional groups in 1,4-disubstituted-5-iodotriazoles are
compatible with the reaction conditions and the 5-trifluoromethyl-1,4-disubstituted triazoles have
been obtained in good to high yields. The addition of Ag2CO3 to the reaction system obviously
increased the yields of the products and the protodehalogenation reaction was suppressed. This is
the first example of direct trifluoromethylation of triazole ring with trifluoromethylating reagent.
4. Experimental
All reagents were of analytical grade, and obtained from commercial suppliers and used without
further purification. DMF and other solvents were dried by standard method prior to use. Melting
points were measured in an open capillary using Büchi melting point B-540 apparatus and are
uncorrected. 1H NMR and 13C NMR spectra were recorded on a 400 spectrometer (400 MHz for 1H
and 100 MHz for 13C NMR, respectively) using TMS as internal standard, The 19F NMR spectra
7
Page 7 of 22

were obtained using a 400 spectrometer (376 MHz). CDCl3 or DMSO-d6 was used as the NMR
solvent in all cases. High resolution mass spectra (HRMS) were recorded under electron impact
conditions using a MicroMass GCT CA 055 instrument and recorded on a MicroMass LCTTM
spectrometer. Silica gel (300−400 mesh size) was used for column chromatography. TLC analysis
of reaction mixtures was performed using silica gel plates.
The synthetic route for the preparation 5a-t is outlined in Scheme 2
Here insert Scheme 2
4.1 Preparation of compounds 3a-i and 4a-g
Compounds 3a-i and 4a-g were synthesized according to the methods reported in the literatures
[27-28]
4.2 Synthesis of 1,4-disubstituted-5-iodo-1,2,3-triazoles (5a-t)
The intermediates 5a-t were synthesized by the reaction of 3a-i with 4a-g in THF in the presence of
CuI [28-29].
1-Benzyl-5-iodo-4-phenyl-1H-1,2,3-triazole (5a): White solid (yield 85%). mp: 138.7–140.3°C. 1H
NMR (400 MHz, CDCl3): δ = 7.99–7.33 (m, 10H), 5.69 (s, 2H); 13C NMR (100 MHz, CDCl3): δ =
150.2, 134.4, 130.3, 128.9, 128.7, 128.6, 128.5, 127.9, 127.5, 76.7, 54.4.
1-Benzyl-5-iodo-4-(p-tolyl)-1H-1,2,3-triazole (5b): White solid (yield 83%). mp: 115.9–117.1°C.
1H NMR (400 MHz, CDCl3): δ = 7.90–7.31 (m, 9H), 5.67 (s, 2H), 2.43 (s, 3H); 13C NMR (100
MHz, CDCl3): δ = 150.2, 138.5, 134.5, 129.3, 128.9, 128.5, 127.9, 127.4, 127.3, 76.5, 54.4, 21.4.
1-Benzyl-5-iodo-4-(4-methoxyphenyl)-1H-1,2,3-triazole (5c): White solid (yield 85%). mp:
129.8–130.8°C. 1H NMR (400 MHz, CDCl3): δ = 7.91–7.00 (m, 9H), 5.68 (s, 2H), 3.87 (s, 3H); 13
C
NMR (100 MHz, CDCl3): δ = 159.9, 150.1, 134.4, 128.9, 128.8, 128.5, 127.8, 122.7, 114.0, 75.8,
55.3, 54.3.
1-Benzyl-4-(4-fluorophenyl)-5-iodo-1H-1,2,3-triazole (5d): White solid (yield 80%). mp:
150.8–152.0°C. 1H NMR (400 MHz, CDCl3): δ = 7.95–7.15 (m, 9H), 5.69 (s, 2H); 13C NMR (100
8
Page 8 of 22

MHz, CDCl3): δ = 162.9 (d, J = 248.0 Hz), 149.5, 134.2, 129.3 (d, J = 8.2 Hz), 129.0, 128.6, 127.8,
126.3 (d, J = 3.3 Hz), 115.6 (d, J = 21.7 Hz), 76.4, 54.5; 19F NMR (376 MHz, CDCl3): δ = -112.6
(s, 1F).
1-Benzyl-4-(4-ethylphenyl)-5-iodo-1H-1,2,3-triazole (5e): White solid (yield 81%). mp:
104.1–104.6°C. 1H NMR (400 MHz, CDCl3): δ =7.91–7.31 (m, 9H), 5.69 (s, 2H), 2.73 (q, J = 7.6
Hz, 2H), 1.30 (t, J = 7.6 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ = 150.3, 144.8, 134.4, 128.9,
128.5, 128.1, 127.8, 127.6, 127.4, 76.2, 54.4, 28.7, 15.5. HRMS (EI): calc. for C17H16IN3 [M]+
389.0389, found 389.0394.
1-Benzyl-5-iodo-4-(phenoxymethyl)-1H-1,2,3-triazole (5f): White solid (yield 80%). mp:
1
104.9–106.0°C. H NMR (400 MHz, CDCl3): δ = 7.38–7.00 (m, 10H), 5.61 (s, 2H), 5.15 (s, 2H);
13C NMR (100 MHz, CDCl3): δ = 158.3, 147.8, 134.1, 129.5, 129.0, 128.6, 127.9, 121.4, 115.1,
80.8, 61.8, 54.3. HRMS (EI): calc. for C16H14IN3O [M]+ 391.0182, found 391.0185.
1-Benzyl-5-iodo-4-((p-tolyloxy)methyl)-1H-1,2,3-triazole (5g): White solid (yield 81%). mp:
1
111.0–112.2°C. H NMR (400 MHz, CDCl3): δ = 7.38–6.95 (m, 9H), 5.62 (s, 2H), 5.12 (s, 2H),
2.32 (s, 3H); 13C NMR (100 MHz, CDCl3): δ = 156.2, 148.0, 134.1, 130.7, 129.9, 128.9, 128.6,
127.9, 115.0, 80.6, 62.0, 54.3, 20.5. HRMS (EI): calc. for C17H16IN3O [M]+ 405.0338, found
405.0342.
5-Iodo-1-phenethyl-4-phenyl-1H-1,2,3-triazole (5h): White solid (yield 89%). mp: 169.1-170.6°C.
1H NMR (400 MHz, CDCl3): δ = 7.96-7.22 (m, 10H), 4.69 (t, J = 8.0 Hz, 2H), 3.29 (t, J = 8.0 Hz,
2H); 13C NMR (100 MHz, CDCl3): δ = 136.7, 130.4, 128.9, 128.6, 127.5, 127.2, 77.3, 52.1, 36.6.
HRMS (EI): calc. for C16H14IN3 [M]+ 375.0232, found 375.0230.
5-Iodo-4-(4-methoxyphenyl)-1-phenethyl-1H-1,2,3-triazole (5i): White solid (yield 83%). mp:
144.1–144.8°C. 1H NMR (400 MHz, CDCl3): δ = 7.88–7.01 (m, 9H), 4.67 (t, J = 7.7 Hz, 2H), 3.88
(s, 3H), 3.27 (t, J = 7.8 Hz, 2H); 13C NMR (100 MHz, CDCl3): δ = 159.9, 149.6, 136.8, 129.0,
128.9, 128.8, 127.2, 122.8, 114.0, 76.5, 55.4, 52.0, 36.6. HRMS (EI): calc. for C17H16IN3O [M]+
405.0338, found 405.0339.
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5-Iodo-4-phenyl-1-(3-phenylpropyl)-1H-1,2,3-triazole (5j): White solid (yield 89%). mp:
128.1–129.1°C. 1H NMR (400 MHz, CDCl3): δ = 7.99–7.27 (m, 10H), 4.47 (t, J = 8.0 Hz, 2H), 2.77
(t, J = 8.0 Hz, 2H), 2.37–2.29 (m, 2H); 13C NMR (100 MHz, CDCl3): δ = 149.7, 140.3, 130.4, 128.7,
128.6, 128.5, 127.5, 126.4, 76.5, 50.3, 32.6, 31.2. HRMS (EI): calc. for C17H16IN3 [M]+ 389.0389,
found 389.0388.
5-Iodo-4-(4-methoxyphenyl)-1-(3-phenylpropyl)-1H-1,2,3-triazole (5k): White solid (yield 80%).
mp: 106.6–107.3°C; 1H NMR (400 MHz, CDCl3): δ = 7.91–7.02 (m, 9H), 4.46 (t, J = 7.3 Hz, 2H),
3.88 (s, 3H), 2.77 (t, J = 7.6 Hz, 2H), 2.36-2.28 (m, 2H); 13C NMR (100 MHz, CDCl3): δ = 159.9,
149.7, 140.3, 128.9, 128.6, 128.5, 126.3, 122.9, 114.0, 75.6, 55.4, 50.3, 32.5, 31.2. HRMS (EI):
calc. for C18H18IN3O [M]+ 419.0495, found 419.0496.
5-Iodo-1-(4-methylbenzyl)-4-phenyl-1H-1,2,3-triazole (5l): White solid (yield 91%). mp:
172.5–174.2°C. 1H NMR (400 MHz, DMSO-d6): δ = 7.91–7.15 (m, 9H), 5.68 (s, 2H), 2.29 (s, 3H);
13C NMR (100 MHz, DMSO-d6): δ = 149.4, 137.8, 132.8, 131.0, 129.8, 129.1, 128.8, 127.9, 127.4,
82.0, 53.76, 21.2. HRMS (EI): calc. for C16H14IN3 [M]+ 375.0232, found 375.0231.
1-(4-Chlorobenzyl)-5-iodo-4-phenyl-1H-1,2,3-triazole (5m): White solid (yield 85%). mp:
1
194.7–196.3°C. H NMR (400 MHz, CDCl3): δ = 7.97–7.95 (m, 2H), 7.51–7.27 (m, 7H), 5.67 (s,
2H); 13C NMR (100 MHz, CDCl3): δ = 150.4, 134.6, 132.8, 130.1, 129.3, 129.2, 128.7, 128.6,
127.4, 76.3, 53.7. HRMS (EI): calc. for C15H11ClIN3 [M]+ 394.9686, found 394.9688.
1-(2-Cyano-benzene-1-yl-methyl)-5-iodo-4-phenyl-1H-1,2,3-triazole (5n): White solid (yield
88%). mp: 214.8–215.3°C. 1H NMR (400 MHz, CDCl3): δ = 8.01–7.77 (m, 3H), 7.62–7.07 (m, 6H),
5.95 (s, 2H); 13C NMR (100 MHz, CDCl3): δ = 150.5, 137.9, 133.7, 133.1, 129.9, 129.0, 128.9,
128.7, 128.1, 127.4, 117.0, 111.6, 77.2, 52.1. HRMS (EI): calc. for C16H11IN4 [M]+ 386.0028,
found 386.0027.
1-(Furan-2-yl-methyl)-5-iodo-4-phenyl-1H-1,2,3-triazole (5o): White solid (yield 70%). mp:
1
124.8–126.2°C. H NMR (400 MHz, CDCl3): δ = 7.97–7.44 (m, 6H), 6.49–6.40 (m, 2H), 5.68 (s,
2H); 13C NMR (100 MHz, CDCl3): δ = 150.1, 147.2, 143.3, 137.2, 130.2, 128.6, 128.5, 127.5,
110.7, 110.3, 76.1, 47.6. HRMS (EI): calc. for C13H10IN3O [M]+ 350.9869, found 350.9873.
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Page 10 of 22

1-(2-Chloro-thiazole-5-yl-methyl)-5-iodo-4-phenyl-1H-1,2,3-triazole (5p): White solid (yield
86%). mp: 189.5–191.1°C. 1H NMR (400 MHz, DMSO-d6): δ = 7.89–7.43 (m, 6H), 5.98 (s, 2H);
13C NMR (100 MHz, DMSO-d6): δ = 152.0, 149.6, 142.1, 135.5, 130.7, 129.2, 129.0, 127.5, 82.0,
46.8. HRMS (EI): calc. for C12H8ClIN4S [M]+ 401.9203, found 401.9195.
1-(2-Chloro-thiazole-5-yl-methyl)-5-iodo-4-((p-tolyloxy)methyl)-1H-1,2,3-triazole (5q): White
solid (yield 87%). mp: 148.6–149.9°C. 1H NMR (400 MHz, CDCl3): δ = 7.65 (s, 1H), 7.12–6.93 (m,
4H), 5.72 (s, 2H), 5.11 (s, 2H), 2.31 (s, 3H); 13C NMR (100 MHz, CDCl3): δ = 156.1, 153.8, 148.2,
141.5, 133.0, 130.8, 130.0, 115.0, 80.2, 61.7, 46.5, 20.5. HRMS (EI): calc. for C14H12ClIN4OS
[M]+ 445.9465, found 445.9465.
1-(2-Chloro-pyridine-5-yl-methyl)-5-iodo-4-phenyl-1H-1,2,3-triazole (5r): White solid (yield
89%). mp: 187.0–187.6°C. 1H NMR (400 MHz, CDCl3): δ = 8.25 (s, 1H), 7.95–7.36 (m, 7H), 5.69
(s, 2H); 13C NMR (100 MHz, CDCl3): δ = 152.0, 150.6, 149.3, 138.6, 129.8, 129.0, 128.9, 128.7,
127.4, 124.8, 76.3, 51.2. HRMS (EI): calc. for C14H10ClIN4 [M]+ 395.9639, found 395.9641.
1-(2-Chloro-pyridine-5-yl-methyl)-5-iodo-4-(p-tolyl)-1H-1,2,3-triazole (5s): White solid (yield
81%). mp: 187.2–188.4°C. 1H NMR (400 MHz, CDCl3): δ = 8.51 (s, 1H), 7.82 (d, J = 8.0 Hz, 2H),
7.64 (d, J = 8.1 Hz, 1H), 7.36 (d, J = 8.2 Hz, 1H), 7.30 (d, J = 7.9Hz, 2H), 5.68 (s, 2H), 2.42 (s, 3H);
13C NMR (100 MHz, CDCl3): δ = 152.0, 150.7, 149.3, 138.9, 138.6, 129.3, 129.1, 127.3, 126.9,
124.8, 76.0, 51.1, 21.4. HRMS (EI): calc. for C15H12ClIN4 [M]+ 409.9795, found 409.9793.
1-(2-Chloro-pyridine-5-yl-methyl)-5-iodo-4-(4-ethylphenyl)-1H-1,2,3-triazole (5t): White solid
(yield 85%). mp: 124.3–125.9°C. 1H NMR (400 MHz, CDCl3): δ = 8.48 (s, 1H), 7.85–7.29 (m, 6H),
5.65 (s, 2H), 2.70 (q, J = 8.0 Hz, 2H), 1.27 (t, J = 8.0 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ =
151.9, 150.6, 149.2, 145.1, 138.6, 129.1, 128.1, 127.4, 127.2, 124.8, 76.3, 51.1, 28.7, 15.4. HRMS
(EI): calc. for C16H14ClIN4 [M]+ 423.9952, found 423.9956.
4.3 General procedure for 5-trifluoromethyl-1,4,5-trisubstituted-1,2,3–triazoles (6a-t) :
To a stirred solution of 5a-t (1.0 mmol), CuI (1.0 mmol, 191 mg), KF (3.0 mmol, 174 mg),
1,10–phenanthroline (1.0 mmol, 180 mg) and Ag2CO3 (2.0 mmol, 552 mg) in dry DMF (15-20 mL)
was added dropwise Me3SiCF3 (3 mmol, 426 mg) via syringe at room temperature. The mixture was
11
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heated to 100 °C and then stirred for 2-3 h (monitored by TLC). The reaction mixture was filtered
through Celite and eluted with CH2Cl2 (20 mL). The combined solution was washed with water (30
mL).The aqueous phase was extracted with CH2Cl2 (3 × 20 mL). The collected organic phase was
washed with brine and then dried with anhydrous Mg2SO4. After filtration and removal of the
solvent, the crude product was purified by column chromatography on silica gel using a petroleum
ether/ethyl acetate (3:1) mixture as eluent to afford the trifluoromethylated compounds 6a-t.
1-Benzyl-4-phenyl-5-(trifluoromethyl)-1H-1,2,3-triazole (6a): White solid (272 mg, yield 90%).
1
mp : 41.4–42.5°C. H NMR (400 MHz, CDCl3): δ = 7.66–7.33 (m, 10H), 5.76 (s, 2H); 13C NMR
(100 MHz, CDCl3): δ = 148.5, 133.9, 129.6, 129.4, 129.0, 128.9, 128.8, 128.5, 127.7, 123.0 (q, 2J =
1
41.1 Hz), 120.4 (q, J = 269.4 Hz), 54.4; 19F NMR (376 MHz, CDCl3): δ = -55.9 (s, 3F); HRMS
(ESI): calc. for C16H13F3N3 [M+H]+ 304.1062, found 304.1054.
1-Benzyl-4-(p-tolyl)-5-(trifluoromethyl)-1H-1,2,3-triazole (6b): White solid (279 mg, yield 88%).
mp: 64.6–65.9°C. 1H NMR (400 MHz, CDCl3): δ = 7.56–7.28 (m, 9H), 5.76 (s, 2H), 2.43 (s, 3H);
13C NMR (100 MHz, CDCl3): δ = 148.6, 139.4, 134.0, 129.2, 129.0, 128.9, 128.8, 127.7, 126.0,
123.0 (q, 2J = 41.2 Hz), 120.6 (q, 1J = 270.1 Hz), 54.4, 21.4; 19F NMR (376 MHz, CDCl3): δ = -55.9
(s, 3F); HRMS (ESI): calc. for C17H15F3N3 [M+H]+ 318.1218, found 318.1216.
1-Benzyl-4-(4-methoxyphenyl)-5-(trifluoromethyl)-1H-1,2,3-triazole (6c): White solid (283 mg,
1
yield 85%). mp: 51.2–52.2°C. H NMR (400 MHz, CDCl3): δ = 7.61–6.99 (m, 9H), 5.75 (s, 2H),
3.87 (s, 3H); 13C NMR (100 MHz, CDCl3): δ = 160.5, 148.4, 134.0, 130.3, 129.0, 128.8, 127.7,
2
1
122.4 (q, J = 40.0 Hz), 121.3, 120.5 (q, J = 269.4 Hz), 114.0, 55.3, 54.4; 19F NMR (376 MHz,
CDCl3): δ = -55.9 (s, 3F); HRMS (ESI): calc. for C17H15F3N3O [M+H]+ 334.1167, found 334.1164.
1-Benzyl-4-(4-fluorophenyl)-5-(trifluoromethyl)-1H-1,2,3-triazole (6d): White solid (260 mg,
yield 81%). mp: 62.6–63.9°C. 1H NMR (400 MHz, CDCl3): δ = 7.65–7.14 (m, 9H), 5.76 (s, 2H) ;
13C NMR (100 MHz, CDCl3): δ = 163.5 (d, J = 249.4 Hz), 147.6, 133.8, 130.9 (d, J = 8.0 Hz),
129.0, 128.9, 127.7, 125.0 (d, J = 3.3 Hz), 122.9 (q, 2J = 40.5 Hz), 120.3 (q, 1J = 269.5 Hz), 115.6
(d, J = 21.9 Hz), 54.5; 19F NMR (376 MHz, CDCl3): δ = -55.9 (s, 3F), -111.5 – -111.6 (m, 1F);
12
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HRMS (ESI): calc. for C16H12F4N3 [M+H]+ 322.0967, found 322.0961.
1-Benzyl-4-(4-ethylphenyl)-5-(trifluoromethyl)-1H-1,2,3-triazole (6e): White solid (281 mg, yield
85%). mp: 45.1–45.4°C; 1H NMR (400 MHz, CDCl3): δ = 7.63–7.32 (m, 9H), 5.76 (s, 2H), 2.74 (q,
J = 7.6 Hz, 2H), 1.30 (t, J = 7.6 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ = 148.6, 145.7, 134.1,
129.0, 128.8, 128.0, 127.7, 126.3, 122.7 (q, 2J = 40.5 Hz), 120.5 (q, 1J = 269.4 Hz), 54.4, 28.7, 15.3;
19F NMR (376 MHz, CDCl3): δ = -55.8 (s, 3F); HRMS (ESI): calc. for C18H16F3N3Na [M+Na]+
354.1194, found 354.1195.
1-Benzyl-4-(phenoxymethyl)-5-(trifluoromethyl)-1H-1,2,3-triazole (6f): Colorless oil (296 mg,
yield 89%). 1H NMR (400 MHz, CDCl3): δ = 7.40–7.00 (m, 10H), 5.70 (s, 2H), 5.25 (s, 2H); 13
C
NMR (100 MHz, CDCl3): δ = 158.2, 144.1, 133.5, 129.5, 129.0, 128.9, 127.8, 125.8 (q, 2J = 41.5
Hz), 121.6, 120.0 (q, 1J = 269.4 Hz), 115.0, 60.8, 54.1; 19F NMR (376 MHz, CDCl3): δ = -57.6 (s,
3F); HRMS (ESI): calc. for C17H14F3N3ONa [M+Na]+ 356.0987, found 356.0972.
1-Benzyl-4-((p-tolyloxy)methyl)-5-(trifluoromethyl)-1H-1,2,3-triazole (6g): Colorless oil (284 mg,
yield 82%). 1H NMR (400 MHz, CDCl3): δ = 7.39–6.91 (m, 9H), 5.69 (s, 2H), 5.22 (s, 2H), 2.32 (s,
3H); 13C NMR (100 MHz, CDCl3): δ = 156.1, 144.3, 133.5, 130.9, 130.0, 129.0, 128.9, 127.8,
2
1
125.8 (q, J = 41.6 Hz), 120.0 (q, J = 269.5 Hz), 114.9, 61.0, 54.1, 20.5; 19F NMR (376 MHz,
CDCl3): δ = -57.6 (s, 3F) ; HRMS (ESI): calc. for C18H16F3N3ONa [M+Na]+ 370.1143, found
370.1125.
1-Phenethyl-4-phenyl-5-(trifluoromethyl)-1H-1,2,3-triazole (6h): Yellow oil (276 mg, yield 87%).
1H NMR (400 MHz, CDCl3): δ = 7.65–7.25 (m, 10H), 4.77 (t, J = 8.0 Hz, 2H), 3.35 (t, J = 8.0 Hz,
2H); 13C NMR (100 MHz, CDCl3): δ = 148.1, 136.3, 129.4, 129.1, 129.0, 128.9, 128.8, 128.5,
127.3, 123.0 (q, 2J = 40.0 Hz), 120.5 (q, 1J = 268.0 Hz), 52.1, 36.7; 19F NMR (376 MHz, CDCl3) δ
= -56.2 (s, 3F); HRMS (ESI): calc. for C17H15F3N3 [M+H]+ 318.1218, found 318.1216.
4-(4-Methoxyphenyl)-1-phenethyl-5-(trifluoromethyl)-1H-1,2,3-triazole (6i): Colorless oil (295
13
Page 13 of 22

mg, yield 85%). 1H NMR (400 MHz, CDCl3): δ = 7.61–7.01 (m, 9H), 4.75 (t, J = 7.8 Hz, 2H), 3.88
(s, 3H), 3.33 (t, J = 7.9 Hz, 2H); 13C NMR (100 MHz, CDCl3): δ = 160.5, 147.9, 136.4, 130.4,
128.9, 128.8, 127.3, 122.5 (q, 2J = 40.0 Hz), 121.4, 120.6 (q, 1J = 269.1 Hz), 114.0, 55.3, 52.1, 36.7;
19F NMR (376 MHz, CDCl3): δ = -56.2 (s, 3F); HRMS (ESI): calc. for C18H17F3N3O [M+H]+
348.1324, found 348.1315.
4-Phenyl-1-(3-phenylpropyl)-5-(trifluoromethyl)-1H-1,2,3-triazole (6j): Yellow oil (278 mg, yield
84%). 1H NMR (400 MHz, CDCl3): δ = 7.70–7.27 (m, 10H), 4.58 (t, J = 8.0 Hz, 2H), 2.81 (t, J =
8.0 Hz, 2H), 2.44–2.36 (m, 2H); 13C NMR (100 MHz, CDCl3): δ = 148.2, 140.0, 129.4,129.1, 129.0,
128.7, 128.5, 128.4, 126.5, 123.0 (q, 2J = 40.0 Hz), 120.5 (q, 1J = 268.0 Hz), 50.4, 32.6, 31.4; 19
F
NMR (376 MHz, CDCl3): δ = -56.2 (s, 3F); HRMS (ESI): calc. for C18H17F3N3 [M+H]+ 332.1375,
found 332.1371.
4-(4-Methoxyphenyl)-1-(3-phenylpropyl)-5-(trifluoromethyl)-1H-1,2,3-triazole (6k): Colorless oil
(299 mg, yield 83%). 1H NMR (400 MHz, CDCl3): δ = 7.63–7.02 (m, 9H), 4.56 (t, J = 7.3 Hz, 2H),
3.87 (s, 3H), 2.78 (t, J = 7.6 Hz, 2H), 2.41–2.33 (m, 2H); 13C NMR (100 MHz, CDCl3): δ = 160.5,
148.0, 140.0, 130.4, 128.6, 128.4, 126.4, 122.4 (q, 1J = 39.9 Hz), 121.4, 120.7 (q, 2J = 269.0 Hz),
114.0, 55.3, 50.4, 32.6, 31.5; 19F NMR (376 MHz, CDCl3): δ = -56.3 (s, 3F); HRMS (ESI): calc. for
C19H19F3N3O [M+H]+ 362.1480, found 362.1491.
1-(4-Methylbenzyl)-4-phenyl-5-(trifluoromethyl)-1H-1,2,3-triazole (6l): Yellow oil (276 mg, yield
87%).1H NMR (400 MHz, CDCl3): δ = 7.64 (s, 2H), 7.48–7.20 (m, 7H), 5.72 (s, 2H), 2.38 (s, 3H);
13C NMR (100 MHz, CDCl3): δ = 148.5, 138.8, 130.9, 129.6, 129.3, 129.0, 128.9, 128.45, 127.7,
122.9, 122.8 (q, 2J = 40.0 Hz), 120.4 (q, 1J = 267.0 Hz), 54.3, 21.2; 19F NMR (376 MHz, CDCl3): δ
= -55.8 (s, 3F); HRMS (ESI): calc. for C17H15F3N3 [M+H]+ 318.1218, found 318.1208.
1-(4-Chlorobenzyl)-4-phenyl-5-(trifluoromethyl)-1H-1,2,3-triazole (6m): White solid (259 mg,
yield 77%). mp: 65.9–67.4°C. 1H NMR (400 MHz, CDCl3): δ = 7.66–7.26 (m, 9H), 5.71 (s, 2H);
13C NMR (100 MHz, CDCl3): δ = 148.6, 134.9, 132.4, 129.5, 129.2, 129.2, 129.0, 128.8, 128.5,
14
Page 14 of 22

122.9 (q, 2J = 40.0 Hz), 120.4 (q, 1J = 268.0 Hz), 53.7; 19F NMR (376 MHz, CDCl3): δ = -55.8 (s,
3F); HRMS (ESI): calc. for C16H12ClF3N3 [M+H]+ 338.0672, found 338.0661.
1-(2-Cyano-benzene-1-yl-methyl)-4-phenyl-5-(trifluoromethyl)-1H-1,2,3-triazole (6n): White
solid (170 mg, yield 52%). mp: 61.2–63.7°C. 1H NMR (400 MHz, CDCl3): δ = 7.79–7.13(m, 9H),
6.02 (s, 2H); 13C NMR (100 MHz, CDCl3): δ = 148.7, 137.4, 133.6, 133.2, 129.6, 129.3, 129.0,
128.6, 128.5, 127.8, 123.4 (q, 2J = 41.0 Hz), 120.2 (q, 1J = 268.0 Hz), 116.3, 111.5, 51.9; 19F NMR
(376 MHz, CDCl3): δ = -55.2 (s, 3F); HRMS (ESI): calc. for C17H12F3N4 [M+H]+ 329.1014, found
329.1016.
1-(Furan-2-yl-methyl)-4-phenyl-5-(trifluoromethyl)-1H-1,2,3-triazole (6o): Yellow oil (161 mg,
1
yield 55%). H NMR (400 MHz, CDCl3): δ = 7.65–7.64 (m, 2H), 7.48–7.47 (m, 4H), 6.52–6.42 (m,
2H), 5.76 (s, 2H); 13C NMR (100 MHz, CDCl3): δ = 148.4, 146.5, 143.7, 129.4, 129.0, 128.8, 128.5,
126.3 (q, 2J = 39.0 Hz), 120.3 (q, 1J = 268.0 Hz), 110.8, 110.2, 47.3; 19F NMR (376 MHz, CDCl3):
δ = -55.8 (s, 3F); HRMS (ESI): calc. for C14H11F3N3O [M+H]+ 294.0854, found: 294.0846.
1-(2-Chloro-thiazole-5-yl-methyl)-4-phenyl-5-(trifluoromethyl)-1H-1,2,3-triazole (6p): Yellow oil
(244 mg, yield 71%). 1H NMR (400 MHz, CDCl3): δ = 7.64–7.48 (m, 6H), 5.87 (s, 2H); 13C NMR
(100 MHz, CDCl3): δ = 154.2, 148.7, 141.7, 132.5, 129.7, 129.0, 128.6, 128.3, 122.6 (q, 2J = 40.0
Hz), 120.3 (q, 1J = 268.0 Hz), 46.5; 19F NMR (376 MHz, CDCl3): δ = -56.0 (s, 3F); HRMS (ESI):
calc. for C13H9ClF3N4S [M+H]+ 345.0183, found 345.0189.
1-(2-Chloro-thiazole-5-yl-methyl)-4-((p-tolyloxy)methyl)-5-(trifluoromethyl)-1H-1,2,3-triazole
(6q): White solid (287 mg, yield 74%). mp: 79.0–80.1°C. 1H NMR (400 MHz, CDCl3): δ = 7.62 (s,
1H), 7.11 (d, J = 8.0 Hz, 2H), 6.91 (d, J = 8.0 Hz, 2H), 5.80 (s, 2H), 5.21 (s, 2H), 2.31 (s, 3H); 13C
NMR (100 MHz, CDCl3): δ = 155.9, 154.3, 144.6, 141.8, 132.1, 131.0, 130.0, 125.6 (q, 2J = 41.0
Hz), 119.9 (q, 1J = 268.0 Hz), 114.8, 60.8, 46.1, 20.5; 19F NMR (376 MHz, CDCl3): δ = -57.3 (s,
3F); HRMS (ESI): calc. for C15H13ClF3N4OS [M+H]+ 389.0451, found 389.0457.
1-(2-Chloro-pyridine-5-yl-methyl)-4-phenyl-5-(trifluoromethyl)-1H-1,2,3-triazole (6r): White
1
solid (236 mg, yield 70%). mp: 59.7–61.1°C. H NMR (400 MHz, CDCl3): δ = 8.44 (s, 1H),
7.67–7.35 (m, 7H), 5.73 (s, 2H); 13C NMR (100 MHz, CDCl3): δ = 152.3, 149.1, 148.7, 138.5,
15
Page 15 of 22

129.6, 129.0, 128.6, 128.4, 124.8, 122.9 (q, 2J = 41.0 Hz), 120.3 (q, 1J = 267.0 Hz), 51.1; 19F NMR
(376 MHz, CDCl3): δ = -55.7 (s, 3F); HRMS (ESI): calc. for C15H11ClF3N4 [M+H]+ 339.0624,
found 339.0617.
1-(2-Chloro-pyridine-5-yl-methyl)-4-(p-tolyl)-5-(trifluoromethyl)-1H-1,2,3-triazole (6s): Colorless
1
oil (264 mg, yield 75%). H NMR (400 MHz, CDCl3): δ = 8.45 (s, 1H), 7.66 (d, J = 8.3 Hz, 1H),
7.51 (d, J = 7.9 Hz, 2H), 7.38 (d, J = 8.3 Hz, 1H), 7.28 (d, J = 7.6 Hz, 2H), 5.73 (s, 2H), 2.42 (s, 3H);
13C NMR (100 MHz, CDCl3): δ = 152.3, 149.1, 148.8, 139.7, 138.4, 129.3, 128.8, 128.6, 125.5,
124.8, 122.6 (q, 2J = 40.4 Hz), 120.3 (q, 1J = 269.4 Hz), 51.0, 21.4; 19F NMR (376 MHz, CDCl3): δ
= -55.7 (s, 3F); HRMS (ESI): calc. for C16H13ClF3N4 [M+H]+ 353.0781, found 353.0781.
1-(2-Chloro-pyridine-5-yl-methyl)-4-(4-ethylphenyl)-5-(trifluoromethyl)-1H-1,2,3-triazole (6t):
Yellow oil (282 mg, yield 77%). 1H NMR (400 MHz, CDCl3): δ = 8.46 (s, 1H), 7.69–7.30 (m, 6H),
5.74 (s, 2H), 2.73 (q, J = 8.0 Hz, 2H), 1.29 (t, J = 8.0 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ =
152.3, 149.0, 148.9, 146.0, 138.5, 128.9, 128.6, 128.1, 125.7, 124.8, 122.6 (q, 2J = 37.0 Hz), 120.3
(q, 1J = 267.0 Hz), 51.1, 28.7, 15.3; 19F NMR (376 MHz, CDCl3): δ = -55.7 (s, 3F); HRMS (ESI):
calc. for C17H15ClF3N4 [M+H]+ 367.0937, found 367.0927.
Acknowledgments
We are grateful for financial supports from the National Natural Science Foundation of China
(Grant No. 21272070, 21072057), the National Basic Research Program of China (973 Program,
2010CB126101), and the Key Project in the National Science & Technology Pillar Program of
China in the twelfth five-year plan period (2011BAE06B05).
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Page 18 of 22

N
N
R1
N
R1
N
N
N
CuI / KF / phen / Ag2CO3 / DMF
+ Me3SiCF3
R2
R2
°
100 C
F3C
I
5a-t
6a-t
Scheme 1. Trifluoromethylation of 5-iodotriazoles with Me3SiCF3.
R1N3
R1OH or R1Cl +
NaN3
N
R1
N
1a-i
+ KI
3a-i
N
CuI, Et3N
THF, r.t.
TBHP
R2
I
R2
R2
I
MeOH, r.t.
2a-g
4a-g
5a-t
Scheme 2. Synthesis of 5a-t via cycloaddition of organic azides 3a-i with 1-iodoalkynes 4a-g.
19
Page 19 of 22

a
Table 1. Optimization of the trifluoromethylation of 5a with Me3SiCF3
N
N
N
N
N
N
N
N
N
[Cu] / KF / phen / additive
solvent, 100 °C
+
+
Me3SiCF3
I
F3C
H
5a
6a
6a'
Yields (%) b
Entry
[Cu] (equiv)
Solvent
Additive (equiv)
6a (6a′)
1
CuI (1.0)
CuI (1.0)
CuI (1.0)
CuI (1.0)
CuI (1.0)
CuI (1.0)
CuI (1.0)
CuI (1.0)
CuI (1.0)
CuI (1.0)
CuI (1.0)
CuI (1.0)
CuI (1.0)
CuI (1.0)
CuI (1.0)
CuI (1.0)
CuI (1.0)
CuI (1.0)
CuI (1.0)
CuI (1.0)
CuI (0.5)
CuI (0.1)
Cu (1.0)
Toluene
CH3CN
THF
None
None
0 (58) c
0 (20) c
0 (98)
46 (50)
63 (32)
68 (28)
56 (43)
65 (7)
0 c
2
3
None
4
CH3NO2
DMSO
DMF
None
5
None
6
None
7
DMF
Ar
8
DMF
O2
9
DMF
K2S2O8 (3.0)
DDQ (3.0)
Cu(OAc)2 (3.0)
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
DMF
5 (72)
17 (82)
31 (57)
80 (20)
99
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
1,4-benzoquinone (3.0)
2,3-dichlorobutane (3.0)
Ag2CO3 (5.0)
Ag2CO3 (4.0)
99
Ag2CO3 (3.0)
98
Ag2CO3 (2.0)
98
Ag2CO3 (1.5)
89 (8)
0 (75) c
0 (51) c
39 (60)
3 (92)
7 (63) c
31 (39)
0 (70) c
89
CH3CO2Ag (3.0)
AgNO3 (3.0)
Ag2CO3 (2.0)
Ag2CO3 (2.0)
Ag2CO3 (2.0)
CuCl (1.0)
Ag2CO3 (2.0)
Cu(OAc)2 (1.0)
CuBr (1.0)
Ag2CO3 (2.0)
Ag2CO3 (2.0)
a Reagents and conditions: 5a (1.0 mmol), Me3SiCF3 (3.0 mmol), phen (1.0 mmol), KF (3.0 mmol),
DMF (15-20 mL), 100 °C, 2-3 h, under air atmosphere.
b Yields were based on GC analysis.
c Starting material was incompletely converted.
20
Page 20 of 22

Table 2. Trifluoromethylation of 5-iodotriazoles 5a-t with Me3SiCF3 mediated by copper iodide a
Me3SiCF3 (3.0 equiv)
N
N
N
R1
CuI (1.0 equiv), KF (3.0 equiv)
N
R1
N
N
phen (1.0 equiv), Ag2CO3 (2.0 equiv)
R2
R2
DMF (15-20mL), 100 °C, 2-3 h
F3C
I
5a-t
6a-t
Isolated
Isolated
yield
Entry
Product
yield
(%)
Entry Product
(%)
N
N
N
N
N
N
N
6k
1
2
90
88
11
83
87
F3C
F3C
OCH3
6a
N
N
N
N
N
6b
6l
H3C
F3C
12
F3C
CH3
N
N
N
Cl
N
N
6c
6m
N
3
4
5
85
81
85
13
77
52
55
F3C
CF3
OCH3
N
N
NC
N
N
6d
N
N
6n
6o
14
F3C
F3C
F
N
N
N
N
N
N
15
6e
O
F3C
F3C
C2H5
N
N
N
N
N
N
S
6f
6p
Cl
F3C
6
89
16
17
71
O
F3C
N
N
N
N
Cl
N
N
6g
N
N
S
F3C
O
7
8
82
87
6q
74
70
O
CH3
CF3
CH3
N
N
N
N
N
6r
N
6h
18
19
20
F3C
N
CF3
Cl
Cl
Cl
N
N
N
N
N
N
OCH3
6s
CH3
9
85
84
75
77
F3C
CF3
N
6i
N
N
N
N
N
N
6j
6t
10
F3C
F3C
N
C2H5
a Reagents and conditions: 5a (1.0 mmol), Me3SiCF3 (3.0 mmol), phen (1.0 mmol), KF (3.0 mmol),
Ag2CO3 (2.0 mmol), DMF (15-20 mL), 100 °C, 2-3 h, under air atmosphere.
21
Page 21 of 22

Research highlights
A new method for the copper-mediated trifluoromethylation of 5-iodotriazole was reported.
The (trifluoromethyl)trimethylsilane was used as trifluoromethylating reagent.
silver carbonate is essential for efficient conversion.
The addition of
22
Page 22 of 22