Copper-mediated trifluoromethylation of terminal alkynes by S-(trifluoromethyl)diarylsulfonium salt

Article abstract of DOI:10.1002/cjoc.201300393

The copper-mediated trifluoromethylation of terminal alkynes with S-(trifluoromethyl)diarylsulfonium salt has been carefully investigated. The reactions proceeded smoothly to afford trifluoromethylated acetylenes in moderate to good yields. This approach is a convenient method to synthesize a variety of functional trifluoromethylated acetylenes. A convenient method for the trifluoromethylation of a variety of terminal alkynes with S-(trifluoromethyl)diarylsulfoniumtriflate in the presence of copper iodide was described. The reactions proceeded smoothly under mild condition to give the desired product in moderate to good yields. Copyright

Full text of DOI:10.1002/cjoc.201300393

FULL PAPER
DOI: 10.1002/cjoc.201300393
Copper-Mediated Trifluoromethylation of Terminal Alkynes by
S-(Trifluoromethyl)diarylsulfonium Salt
Xiaoping Wang,a,b Jinhong Lin,a Chengpan Zhang,a Jichang Xiao,*,a and Xing Zhengb
aKey Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry,
Chinese Academy of Sciences, Shanghai 200032, China
bInstitute of Pharmacy and Pharmacology, University of South China, Hengyang, Hunan 421001, China
The copper-mediated trifluoromethylation of terminal alkynes with S-(trifluoromethyl)diarylsulfonium salt has
been carefully investigated. The reactions proceeded smoothly to afford trifluoromethylated acetylenes in moderate
to good yields. This approach is a convenient method to synthesize a variety of functional trifluoromethylated
acetylenes.
Keywords copper, alkynes, trifluoromethylation, S-(trifluoromethyl)diarylsulfonium salt
Introduction
ing reagent, Togni’s reagent or Umemoto’s reagent,
could also achieve trifluoromethylation of terminal al-
kynes by utilizing copper complex as catalyst.[7] While
in the case of Umemoto’s reagent, only moderate yields
were obtained for aliphatic alkynes and low yields were
obtained for aromatic alkynes.[7a]
S-(Trifluoromethyl)diarylsulfonium salts, which
were first prepared by Yagupolskii and then developed
by Umemoto, Shreeve and Shibata, have been success-
fully used for the electrophilic trifluoromethylation of
nucleophiles.[8] We have shown that one of these re-
agents could be able to achieve trifluoromethylation of
heteroaromatic compounds, arylboronic acids and sty-
renes.[3r,9] We then further investigated the use of this
reagent in the copper-mediated trifluoromethylation of
terminal alkynes.
Trifluoromethylated organic compounds are becom-
ing increasingly important in the fields of polymers,
agrochemicals, and pharmaceuticals due to the unique
characteristics of the trifluoromethyl group (CF3), such
as metabolic stability and hydrophobicity.[1] As a con-
sequence, the development of efficient methods for
trifluoromethylation has been of great synthetic interest
for organic chemists and medicinal chemists re-
cently.[1c,2] Traditional methods, which involve radical,
nucleophilic or electrophilic trifluoromethylation re-
agents and usually focus on non-catalytic trifluoro-
methylation reactions, suffer from harsh reaction condi-
tions and limited substrate scope.[1a,1b] Recently, con-
siderable progress has been made on the transition
metal-mediated coupling reactions for trifluoromethyla-
tion.[3] In these approaches, copper has been shown to
be one of the most efficient transition metals for
trifluoromethylation.[3q-3w]
Trifluoromethylated acetylenes are a class of impor-
tant fluorinated building blocks and have found wide-
spread applications in medicinal chemistry, agrochem-
istry and material science.[4] The first copper-mediated
oxidative trifluoromethylation of terminal alkynes with
Me3SiCF3 was reported by Qing and coworkers.[5] This
approach is a straightforward and functional group
compatible method for a broad range of trifluoromethy-
lated acetylenes, but the limitations such as high reac-
tion temperature and the use of large amount of
TMSCF3 prompted them to find a better way to achieve
the trifluoromethylation under milder conditions.[6] Re-
cently, it was found that electrophilic trifluromethylat-
Experimental
1H and 13C NMR spectra were recorded at 300 and
100 MHz, respectively, with TMS as the internal stan-
dard. 19F NMR spectra were recorded at 282 MHz with
CFCl3 (positive for downfield shifts) as the external
standards. High resolution mass data were recorded on a
Waters Micromass GCT Preminer instrument. Melting
points were obtained on SYP1008-3 instrument. All
reactions were monitored by TLC with Huanghai GF254
silica gel coated plates. Flash column chromatography
was carried out using 300－400 mesh silica gel.
General procedure for the trifluoromethylation of
terminal alkynes: into the solution of terminal alkyne
(0.2 mmol) in DMF (6 mL) was added [Ph2SCF3]＋[OTf]－
(160.0 mg, 0.40 mmol), followed by CuI (39.1 mg, 0.2
*
E-mail: jchxiao@sioc.ac.cn; Tel.: 0086-021-54925340; Fax: 0086-021-64166128
Received May 10, 2013; accepted June 17, 2013; published online July 19, 2013.
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/cjoc.201300393 or from the author.
Chin. J. Chem. 2013, 31, 915—920
© 2013 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
915

Wang et al.
FULL PAPER
mmol), 2,2'-bipyridine (33.0 mg, 0.2 mmol) and K3CO3
(32.0 mg, 0.2 mmol). The reaction mixture was stirred
at 60 ℃ for 6－11 h. After cooling to room tempera-
ture, the mixture was diluted with diethyl ether, washed
with H2O, dried over Na2SO4, and concentrated under
reduced pressure. The residue was purified by column
chromatography on silica gel [eluent: petroleum
ether/ethyl acetate (20∶1, V∶V)] to give the desired
product.
CDCl3) δ: −49.76 (s, 3F).
Methyl
2-(3,3,3-trifluoroprop-1-yn-1-yl)benzoate
(2i):[6a] 1H NMR (300 MHz, CDCl3) δ: 8.03－7.95 (m,
1H), 7.59－7.28 (m, 3H), 3.88 (s, 3H); 19F NMR (282
MHz, CDCl3) δ: −49.78 (s, 3F).
Methyl
4-(3,3,3-trifluoroprop-1-yn-1-yl)benzoate
(2j):[10d] 1H NMR (300 MHz, CDCl3) δ: 8.00 (d, J＝8.1
Hz, 2H), 7.57 (d, J＝8.1 Hz, 2H), 3.88 (s, 3H); 19F
NMR (282 MHz, CDCl3) δ: −49.48 (s, 3F).
(3,3,3-Trifluoroprop-1-yn-1-yl)benzene (2a):[10a] 1H
NMR (300 MHz, CDCl3) δ: 7.56 (d, J＝7.6 Hz, 2H),
7.47 (d, J＝7.4 Hz, 1H), 7.40 (t, J＝7.6 Hz, 2H); 19F
NMR (282 MHz, CDCl3) δ: −48.77 (s, 3F).
4-(3,3,3-Trifluoroprop-1-yn-1-yl)benzonitrile (2k):[10e]
1H NMR (300 MHz, CDCl3) δ: 7.66－7.22 (m, 4H); 19F
NMR (282 MHz, CDCl3) δ: −49.76 (s, 3F).
5-(3,3,3-Trifluoroprop-1-yn-1-yl)-1H-indole (2l): A
1
1-Propyl-4-(3,3,3-trifluoroprop-1-yn-1-yl)benzene
(2b):[10b] 1H NMR (300 MHz, CDCl3) δ: 7.47 (d, J＝7.8
Hz, 2H), 7.20 (d, J＝7.8 Hz, 2H), 2.62 (t, J＝7.8 Hz,
2H), 1.71－1.49 (m, 2H), 0.94 (t, J＝7.5 Hz, 3H); 19F
NMR (282 MHz, CDCl3) δ: −49.55 (s, 3F).
1-(tert-Butyl)-4-(3,3,3-trifluoroprop-1-yn-1-yl)ben-
zene (2c):[5] 1H NMR (300 MHz, CDCl3) δ: 7.49 (d, J＝
8.1 Hz, 2H), 7.41 (d, J＝8.1 Hz, 2H), 1.32 (s, 9H); 19F
NMR (282 MHz, CDCl3) δ: −49.18 (s, 3F).
white solid. M.p. 109－110 ℃. H NMR (300 MHz,
CDCl3) δ: 8.30 (s, 1H), 7.90 (s, 1H), 7.40－7.27 (m,
3H), 6.58 (s, 1H); 19F NMR (282 MHz, CDCl3) δ:
−48.96 (s, 3F); 13C NMR (100 MHz, CDCl3) δ: 136.70,
127.74, 126.30 (q, J＝2.1 Hz), 125.81 (q, J＝1.5 Hz),
125.70, 115.32 (q, J＝254.4 Hz), 111.51, 109.54 (q, J＝
1.4 Hz), 103.3, 88.93 (q, J＝6.6 Hz), 73.92 (q, J＝51.8
Hz); IR (KBr) ν: 3404, 2243, 1324, 1327, 1307, 1263,
1208, 1109, 1088, 898, 814, 766, 732, 607 cm−1.
GC-MS: 209 (M ＋ ). HRMS calced for C11H6F3N:
209.0452; found 209.0451.
4-(3,3,3-Trifluoroprop-1-yn-1-yl)-1,1'-biphenyl
(2d):[10c] 1H NMR (300 MHz, CDCl3) δ: 7.64－7.59 (m,
6H), 7.50－7.40 (m, 3H); 19F NMR (282 MHz, CDCl3)
δ: −49.33 (s, 3F).
1-(5-(3,3,3-Trifluoroprop-1-yn-1-yl)thiophen-2-yl)-
ethanone (2m): A yellow solid. M.p. 49－50 ℃. H
1
2-(3,3,3-Trifluoroprop-1-yn-1-yl)-9H-fluorene (2e):
NMR (300 MHz, CDCl3) δ: 7.60 (d, J＝3.9 Hz, 1H),
7.44 (d, J＝3.9 Hz, 1H), 2.61 (s, 3H); 19F NMR (282
MHz, CDCl3) δ: −48.78 (s, 3F); 13C NMR (100 MHz,
CDCl3) δ: 189.81, 147.90, 136.17 (q, J＝1.6 Hz),
131.50, 124.93 (q, J＝2.3 Hz), 114.58 (q, J＝256.7 Hz),
81.43 (q, J＝53.7 Hz), 79.23 (q, J＝6.3 Hz), 26.89; IR
(KBr) ν: 3085, 2242, 1663, 1449, 1262, 1132, 821, 749,
650, 608, 587 cm−1. GC-MS: 218 (M＋). HRMS calcd
for C9H5F3OS: 218.0013; found 218.0016.
N-Benzyl-4,4,4-trifluoro-N-methylbut-2-yn-1-amine
(2n):[5] 1H NMR (300 MHz, CDCl3) δ: 7.39－7.24 (m,
5H), 3.58 (s, 2H), 3.42 (q, J＝2.9 Hz, 2H), 3.38 (s, 3H).
19F NMR (282 MHz, CDCl3) δ: −49.60 (s, 3F).
1
A white solid. M.p. 99－100 ℃. H NMR (300 MHz,
CDCl3) δ: 7.79 (t, J＝7.3 Hz, 2H), 7.72 (s, 1H), 7.57 (d,
J＝7.7 Hz, 2H), 7.48－7.30 (m, 2H), 3.91 (s, 2H); 19F
NMR (282 MHz, CDCl3) δ: −49.47 (s, 3F); 13C NMR
(100 MHz, CDCl3) δ: 144.39 (s), 143.74 (s), 143.26 (s),
140.37 (s), 131.40 (s), 128.96 (s), 127.95 (s), 127.09 (s),
125.18 (s), 120.61 (s), 119.97 (s), 116.11 (q, J＝1.8 Hz),
114.97 (q, J＝256.6 Hz), 87.48 (q, J＝6.4 Hz), 75.53 (q,
J＝52.3 Hz), 36.68 (s); IR (KBr) ν: 2265, 2229, 1610,
1485, 1466, 1456, 1420, 1398, 1339, 1321, 1297, 1235,
1191, 1180, 1131, 1103, 862, 770, 735, 698, 600 cm−1.
GC-MS: 258 (M＋). HRMS calcd for C16H9F3: 258.0656;
found 258.0652.
1-Methoxy-4-(3,3,3-trifluoroprop-1-yn-1-yl)benzene
(2f):[10a] 1H NMR (300 MHz, CDCl3) δ: 7.49 (d, J＝8.7
Hz, 2H), 6.89 (d, J＝8.7 Hz, 2H), 3.83 (s, 3H); 19F
NMR (282 MHz, CDCl3) δ: −49.36 (s, 3F).
Results and Discussion
The trifluoromethylation of phenylacetylene (1a)
with [Ph2SCF3]＋[OTf]－(3) was selected as a model re-
action (Table 1). The reactions were performed in the
presence of copper complex and sodium acetate in DMF
at 60 ℃ for 6 h (Entries 1－13). Of the copper com-
plexes screened, Cu(I) was found to be more effective
than copper(II) or copper powder (Entries 1－6). Cop-
per powder could lead to the reduction of [Ph2SCF3]＋
[OTf]－ but only trace amount of desired product was
1-Ethoxy-4-(3,3,3-trifluoroprop-1-yn-1-yl)benzene
(2g): A colorless liquid. 1H NMR (300 MHz, CDCl3) δ:
7.46 (d, J＝8.7 Hz, 2H), 6.68 (d, J＝8.7 Hz, 2H), 4.05
(q, J＝6.9 Hz, 2H), 1.43 (t, J＝6.9 Hz, 3H); 19F NMR
(282 MHz, CDCl3) δ: −49.32 (s, 3F); 13C NMR (100
MHz, CDCl3) δ: 161.02, 134.16 (q, J＝1.5 Hz), 115.13
(q, J＝254.5 Hz), 114.79, 110.11, 87.22 (q, J＝5.8 Hz),
74.75 (q, J＝51.8 Hz), 63.73, 14.58; IR (KBr) ν: 2990,
2250, 1606, 1510, 1478, 1291, 1254, 1135, 1044, 836,
772, 577, 537 cm−1. GC-MS: 214 (M＋). HRMS calcd
for C11H9F3O: 214.0605; found 214.0604.
19
detected by F NMR (Entry 5). The ligand is quite im-
portant for the reaction (Entries 7－13). It was found
that 1 equiv. of bipy (2,2'-bipyridine) as ligand gave
better result (Entry 4 vs. Entries 7－13). Worse results
were obtained if the reaction temperature was varied
(Entry 4 vs. Entries 14 and 15). Based on these first re-
sults, we decided to further screen the reaction condi-
1-Bromo-4-(3,3,3-trifluoroprop-1-yn-1-yl)benzene
(2h):[5] 1H NMR (300 MHz, CDCl3) δ: 7.55 (d, J＝7.5
19
Hz, 2H), 7.42 (d, J＝7.5 Hz, 2H); F NMR (282 MHz,
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© 2013 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2013, 31, 915—920

Copper-Mediated Trifluoromethylation of Terminal Alkynes
Table 1 Screening for optimal conditions for the trifluoromethylation of phenylacetylene by [Ph2SCF3]＋[OTf]－
Metal, ligands (1.0 equiv.)
a
R
CF3
+
R
S
Base (1.0 equiv.)/Solvent
Temp., time
OTf
CF3
2a
1a
3
Entry
1
1a∶3∶M (equiv.)b
1∶1∶CuCl (1.0)
1∶1∶CuBr (1.0)
1∶1∶CuCl2 (1.0)
1∶1∶CuI (1.0)
1∶1∶Cu (1.0)
1∶1∶CuOTf (1.0)
1∶1∶CuI (1.0)
1∶1∶CuI (1.0)
1∶1∶CuI (1.0)
1∶1∶CuI (1.0)
1∶1∶CuI (1.0)
1∶1∶CuI (1.0)
1∶1∶CuI (1.0)
1∶1∶CuI (1.0)
1∶1∶CuI (1.0)
1∶1∶CuI (1.0)
1∶1∶CuI (1.0)
1∶1∶CuI (1.0)
1∶1∶CuI (0.1)
1∶1∶CuI (2.0)
1∶2∶CuI (1.0)
1∶3∶CuI (1.0)
1∶4∶CuI (1.0)
1∶2∶CuI (1.0)
1∶2∶CuI (1.0)
1∶2∶CuI (1.0)
1∶2∶CuI (1.0)
1∶2∶CuI (1.0)
1∶1∶CuI (1.0)
1∶2∶CuI (1.0)
1∶2∶CuI (1.0)
Ligand
Base
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaHCO3
K3PO4
Solvent
Temp., Time
60 ℃, 6 h
60 ℃, 6 h
60 ℃, 6 h
60 ℃, 6 h
60 ℃, 6 h
60 ℃, 6 h
60 ℃, 6 h
60 ℃, 6 h
60 ℃, 6 h
60 ℃, 6 h
60 ℃, 6 h
60 ℃, 6 h
60 ℃, 6 h
80 ℃, 6 h
R.T., 6 h
Yield (2a, %)c
Bipy
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
CH3CN
THF
34
36
2
Bipy
3
Bipy
4
4
Bipy
47
5
Bipy
complex
22
6
Bipy
7
—
12
8
Benzo[h]quinoline
10
9
Py
Phen
18
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
40
2,6-Dimethylpyridine
DPPP
DPPF
Bipy
15
30
16
43
Bipy
40
Bipy
60 ℃, 6 h
60 ℃, 6 h
60 ℃, 6 h
60 ℃, 6 h
60 ℃, 6 h
60 ℃, 6 h
60 ℃, 6 h
60 ℃, 6 h
60 ℃, 6 h
60 ℃, 6 h
60 ℃, 6 h
60 ℃, 6 h
60 ℃, 6 h
60 ℃, 6 h
60 ℃, 3 h
60 ℃, 10 h
20
Bipy
complex
15
Bipy
DMSO
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
Bipy
6
Bipy
48
Bipy
70
Bipy
75
Bipy
68
Bipy
66
Bipy
52
Bipy
K2CO3
DABCO
DMAP
—
90
Bipy
trace
20
Bipy
Bipy
10
Bipy
K2CO3
K2CO3
85
Bipy
DMF
90
a
c
Reaction conditions: 1a (0.1 mmol), 3 (0.1 mmol), DMF (3 mL). b Molar ratio. Yield of 2a determined by 19F NMR. Bipy＝
2,2'-bipyridine, DPPP＝1,3-bis(diphenylphosphino)propane, DPPF＝1,1'-bis(diphenylphosphino)ferrocene.
tions in the presence of CuI and 1 equiv. of bipy at 60
℃.
the reaction was examined (Entries 21－23). When 2
equiv. of this salt was used, the yield was improved (En-
try 21 vs. 4). 3 equiv. of salt gave slightly better yield
(Entry 22). But further increasing the amount of salt
gave lower yield (Entry 23). Obviously, 2 equiv. of salt
was a better choice than 3 equiv. because of the similar
result and the cost.
Both of inorganic bases and organic bases were
screened (Entries 24－28). Inorganic bases gave mod-
erate to excellent yields but organic bases gave very low
yields. The low yields might be because the presence of
Some other polar solvents, such as CH3CN, THF,
DMSO, were also investigated (Entries 16－18). Of
these solvents, DMF was the best choice (Entry 4 vs.
Entries 16－18). Reducing the amount of CuI led to
dramatic decrease of the yield (Entry 19). Increasing its
amount to 2 equiv. did not increase the yield (Entry 20
vs. Entry 4). So 1 equiv. of CuI was adopted to be the
optimal amount.
The effect of the amount of [Ph2SCF3]＋[OTf]－ on
Chin. J. Chem. 2013, 31, 915—920
© 2013 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
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Wang et al.
FULL PAPER
organic base would lead to the decomposition of
[Ph2SCF3]＋[OTf]－. Without the presence of any base,
only small amount of desired product was detected (En-
try 29). It can be clearly seen that K2CO3 was the best
choice.
The reaction time shows some effect on the yield
(Entries 30 and 31). Shortening the time led to lower
yield (Entry 30). Prolonging the time to 10 h gave the
same yield as that of 6 h (Entry 31 vs. 26), which means
the reaction was complete in 6 h. After the screening of
the reaction condition, we determined that the optimal
reaction condition was that 1∶2∶1 ratio of akyn∶
[Ph2SCF3]＋[OTf]－∶CuI, 1 equiv. of bipy as ligand,
K2CO3 as base, DMF as solvent, reaction at 60 ℃ for 6
h.
With the optimized conditions in hand, we further
investigated the scope of the CuI-mediated trifluoro-
methylation of terminal alkynes and, as shown in Figure
1, found that the reaction could tolerate various func-
tional groups. Substrates with electron-donating groups
were converted smoothly into the products with moder-
ate to good yields (2b－2g). We have found that iodo-
benzene could be trifluoromethylated by [Ph2SCF3]＋-
[OTf]－ in the presence of copper powder.[3r] So we
were concerned that bromine substituent on the phenyl
group might interfere with the desired reaction. How-
ever, to our surprise, not any sign of trifluoromethylated
phenyl product was detected in 19F NMR. The desired
product was obtained in 67% of isolated yield (2h). In
the case of other substrates with electron-withdrawing
groups, the reactions also proceeded smoothly to give
the expected products in moderate to good yields (2i－
2k). It was found that the steric effect shows no side
effect on the reaction (2i).
Examples of heteroaromatic and aliphatic substrates
were also examined (2l－2n). When screening the reac-
tion conditions, we found that the strong organic base
would lead to the decomposition of [Ph2SCF3]＋[OTf]－
(Table 1, Entries 27 and 28). But no obvious negative
effect was observed for the substrates containing weaker
basic group (2n). The desired products could still be
obtained in good yield.
The 19F NMR of all of the reaction mixtures before
work-up showed that there were four signals: expected
products, CF3I, CF3H and OTf. If CuBr or CuCl was
used instead of CuI, CF3Br or CF3Cl would be obtained.
If KI was used instead of CuI, no CF3I was detected.
Combined with the results achieved above, the mecha-
nism for this reaction was proposed in Scheme 1. Cop-
per complex (I) is oxidated to a Cu(III)-complex (III)
intermediate, which undergoes reductive elimination to
give CF3I or ligand exchange to give intermediate IV.
Another possibility is that the ligand exchange of iodine
substituent in intermediate I with alkyne anion would
give intermediate IV. The reductive elimination of in-
termediate IV affords the desired product.
CuI/Bipy
R
+
R
CF3
S
K2CO3 / DMF
60 oC, 6 h
OTf
CF3
_
_
1b 1n
2b 2n
3
CF3
Ph
CF3
2d(82%, 80%b)
CF3
CF3
2b (84%, 71%b)
2c (81%, 67%b)
2e (81%, 75%b)
CF3
O
CF3
Br
CF3
O
O
O
CF3
2f (94%, 86%b)
2g (96%, 83%b)
2h (76%, 67%b)
2i (80%, 72%b)
F3C
O
O
N
CF3
CF3
S
F3C
O
N
H
2m (68%, 60%b)
2k (66%, 62%b)
2l (51%, 50%b)
2j (77%, 76%b)
N
CF3
2n (83%, 74%b)
Figure 1 CuI-mediated trifluoromethylation of terminal alkynes (the molar ratio of 1b－1n∶3∶CuI∶Bipy∶K2CO3 was 1∶2∶1∶1.
The yield was determined by 19F NMR. b Isolated yield).
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© 2013 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2013, 31, 915—920

Copper-Mediated Trifluoromethylation of Terminal Alkynes
Scheme 1 Proposed mechanism for the trifluoromethylation of terminal alkynes
+
CuI
N
N
R
+
N
N
base
CuI
I
S
S
OTf
CF3
OTf
CF3
(I)
path I
path II
N
N
CuI
R
OTf
CuIII
CF3I
OTf
N
N
N
N
(II)
R
CuIII
I
CF3
(IV)
CF3
(III)
path IIa
path IIb
N
N
CuI OTf
(V)
R
+
base
OTf
N
N
CuIII
R
R
CF3
CF3
(IV)
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6039; (j) Zhang, L.-S.; Chen, K.; Chen, G.; Li, B.-J.; Luo, S.; Guo,
Q.-Y.; Wei, J.-B.; Shi, Z.-J. Org. Lett. 2012, 15, 10; (k) Zhang,
X.-G.; Dai, H.-X.; Wasa, M.; Yu, J.-Q. J. Am. Chem. Soc. 2012, 134,
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Soc. 2012, 134, 6976; (m) Liu, T.; Shao, X.; Wu, Y.; Shen, Q.-L.
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D.; Buchwald, S. L. Angew. Chem., Int. Ed. 2012, 51, 2947; (o) Wu,
X.; Chu, L.; Qing, F.-L. Angew. Chem., Int. Ed. 2013, 52, 2198; (p)
Zeng, Y.; Zhang, L.; Zhao, Y.; Ni, C.; Zhao, J.; Hu, J. J. Am. Chem.
Soc. 2013, 135, 2955; (q) Chu, L.; Qing, F.-L. J. Am. Chem. Soc.
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C.-T.; Gu, Y.-C.; Xiao, J.-C. Angew. Chem., Int. Ed. 2011, 50, 1896;
(s) Deng, Q.-H.; Wadepohl, H.; Gade, L. H. J. Am. Chem. Soc. 2012,
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Conclusions
In summary, we have developed a convenient
method for the trifluoromethylation of a variety of ter-
minal alkynes with S-(trifluoromethyl)diarylsulfonium
triflate in the presence of copper iodide. The reaction
could tolerate various functional groups. In the case of
substrates substituted by weak basic groups, the reaction
still proceeded smoothly to give the desired products.
Investigation on the application of the trifluoromethyla-
tion method to the synthesis of pharmaceuticals and
agrochemicals is currently underway.
Acknowledgement
We thank the National Natural Science Foundation
of China (Nos. 21032006, 21172240), the 973 Program
of China (No. 2012CBA01200), the Chinese Academy
of Sciences for financial support.
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Chin. J. Chem. 2013, 31, 915—920