Cu(I)/Ag(I)-mediated decarboxylative trifluoromethylation of arylpropiolic acids with Me3SiCF3at room temperature

Article abstract of DOI:10.1016/j.tet.2016.05.012

A novel Cu(I)/Ag(I)-mediated decarboxylative trifluoromethylation of arylpropiolic acids with Me₃SiCF₃has been developed for the construction of Csp-CF₃bond under mild conditions. This method proceeds smoothly at room temperature and shows a widely functional compatibility, providing a series of corresponding trifluoromethylated acetylenyl-containing aromatics in good yields.

Full text of DOI:10.1016/j.tet.2016.05.012

Accepted Manuscript
Cu(I)/Ag(I)-mediated decarboxylative trifluoromethylation of arylpropiolic acids with
Me SiCF at room temperature
3
3
Lingling Yang, Linlin Jiang, Yaming Li, Xinmei Fu, Rong Zhang, Kun Jin, Chunying
Duan
PII:
S0040-4020(16)30385-4
10.1016/j.tet.2016.05.012
TET 27739
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 25 January 2016
Revised Date: 2 May 2016
Accepted Date: 3 May 2016
Please cite this article as: Yang L, Jiang L, Li Y, Fu X, Zhang R, Jin K, Duan C, Cu(I)/Ag(I)-mediated
decarboxylative trifluoromethylation of arylpropiolic acids with Me SiCF at room temperature,
3
3
Tetrahedron (2016), doi: 10.1016/j.tet.2016.05.012.
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to
our customers we are providing this early version of the manuscript. The manuscript will undergo
copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please
note that during the production process errors may be discovered which could affect the content, and all
legal disclaimers that apply to the journal pertain.

ACCEPTED MANUSCRIPT
Graphical Abstract
To create your abstract, type over the instructions in the template box below.
Fonts or abstract dimensions should not be changed or altered.
Cu(I)/Ag(I)-Mediated Decarboxylative Trifluoromethylation
Of Arylpropiolic Acids with Me3SiCF3 at Room Temperature
Lingling Yang, Linlin Jiang, Yaming Li*, Xinmei Fu,
Rong Zhang, Kun Jin and Chunying Duan*
Leave this area blank for abstract info.
State Key Laboratory of Fine Chemicals, School of Chemical Engineering,
Dalian University of Technology, Dalian 116024, Liaoning, P.R.China

ACCEPTED MANUSCRIPT
1
Tetrahedron
journal homepage: www.elsevier.com
Cu(I)/Ag(I)-Mediated Decarboxylative Trifluoromethylation of Arylpropiolic Acids
with Me3SiCF3 at Room Temperature
Lingling Yanga, Linlin Jianga, Yaming Lia,*, Xinmei Fua, Rong Zhanga, Kun Jina and Chunying Duana
a State Key Laboratory of Fine Chemicals, School of Chemical Engineering, Dalian University of Technology, Dalian 116024, Liaoning, P.R.China
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
A novel Cu(I)/Ag(I)-mediated decarboxylative trifluoromethylation of arylpropiolic acids with
Me3SiCF3 has been developed for the construction of Csp-CF3 bond under mild conditions. This
method proceeds smoothly at room temperature and shows a widely functional compatibility,
providing a series of corresponding trifluoromethylated acetylenyl-containing aromatics in good
yields.
Available online
2009 Elsevier Ltd. All rights reserved
.
Keywords:
Trifluoromethylation
Decarboxylative coupling reaction
Arylpropiolic acids
Trifluoromethylated acetylenes
Cu(I)/Ag(I)-mediated
1. Introduction
limitation that some of terminal alkynes are cumbersomely
handled because of their relatively low boiling points.8
The trifluoromethyl derivatives are widely used in
agrochemicals, pharmaceuticals and materials,1,2 since
incorporation of trifluoromethyl groups into the organic
molecules brings remarkable changes in their physical, chemical,
and biological properties because of the strong electronic
properties, lipophilicity and metabolic stability of the
trifluoromethyl group.1 Although a number of methods for the
construction of Csp3-CF3 bonds3,4 and Csp2-CF3 bonds4e,5 have
been reported during the past years, few reactions are applicable
for the construction of Csp-CF3 bonds.5g,6,7 In addition, few
reactions with nucleophilic reagents have been studied. Recently,
the Qing’s group (Scheme 1a)6 and Hu’s group(Scheme 1b)7a
have successfully discovered the possibility of generating “Cu-
Compared to terminal alkynes, the arylpropiolic acids as
alkyne sources have many advantages. They are usually solid-
state without strong smells and easy to store and handle.9,10a-c
Besides, the synthetic procedures and purification of
arylpropiolic acids are easier and simpler.10d Therefore, using
arylpropiolic acids as alkyne sources would make the process
safer and easier to operate.10c,12fSince 2008, a variety of
decaroxylative coupling reactions of alkynyl carboxylic acids
have been developed by Lee’s group8,10,11 and others,12,13
including the formation of C-C, C-N, C-S, C-P bonds. However,
decarboxylative coupling reactions with Csp3 groups are rare.
Lee’s group10d and Satya12g et al respectively reported that the
decarboxylative coupling reaction of arylpropiolic acids with
ICH2CH3 and SN2′ allylic coupling of acetates of the Baylis–
Hillman alcohols form the corresponding Csp-Csp3 bonds
directly. As far as we know, the formation of Csp-CF3 bonds
through the coupling of arylpropiolic acids with
trifluoromethylating reagents has not been reported. Instead of
CF3-substituted alkynes, Hu’s group14 obtained the α-
trifluoromethyl ketones using phenylpropiolic acid as the
substrate. Herein, we developed a new and mild process for
Cu(I)/Ag(I)-mediated decarboxylative trifluoromethylation of
arylpropiolic acids at room temperature to construct Csp-CF3
bond by using cheap Me3SiCF3.
CF3”complex
from
Cu(I)
salts
and
nucleophilic
trifluoromethylating reagents respectively. The kind of complex
could be reacted with terminal alkynes, affording the
corresponding trifluoromethylated arylacetylenes in good yields.
Usually, terminal alkynes have been employed as alkyne sources
Scheme 1. Formation of Csp-CF3bond with nucleophilic
trifluoromethylating reagents
for the synthesis of Csp-CF3 bonds. However, there is a
Yaming Li. Tel.: +86-411-84986295; fax: +86-411-84986295; e-mail: ymli@dlut.edu.cn

ACCEPTED MANUSCRIPT
2
Tetrahedron
Table 1. Optimization of reaction conditions
Entrya,b
Catalyst[Cu]
Ligand
Oxidant
Yield of 2a %
1c
2c
phen (1.0 equiv)
phen (1.0 equiv)
Ag2CO3 (2.0 equiv)
Ag2CO3 (2.0 equiv)
33
38
CuI (1.0 equiv), 70 ℃
CuI (1.0 equiv), r.t.
3
CuI (1.0 equiv), r.t.
phen (1.0 equiv)
Ag2CO3 (2.0 equiv)
89
4
5
CuBr (1.0 equiv), r.t.
CuCl (1.0 equiv), r.t.
Cu(OAc)2 (1.0 equiv), r.t.
CuI (1.0 equiv), r.t.
CuI (1.0 equiv), r.t.
CuI (1.0 equiv), r.t.
CuI (1.0 equiv), r.t.
CuI (1.0 equiv), r.t.
CuI (1.0 equiv), r.t.
CuI (0.5 equiv), r.t.
CuI (0.1 equiv), r.t.
CuI(1.0 equiv), r.t.
phen (1.0 equiv)
phen (1.0 equiv)
hen (1.0 equiv)
bpy (1.0 equiv)
TMEDA (1.0 equiv)
phen (1.0 equiv)
phen (1.0 equiv)
phen (1.0 equiv)
phen (1.0 equiv)
phen (0.5equiv)
phen (0.1equiv)
phen (1.0 equiv)
Ag2CO3 (2.0 equiv)
Ag2CO3 (2.0 equiv)
Ag2CO3 (2.0 equiv)
Ag2CO3 (2.0 equiv)
Ag2CO3 (2.0 equiv)
Air
77
72
n.r
77
83
21
23
16
20
78
11
57
6
7
8
9
10
11
12d
13
14e
15
O2
Cu(OAc)2 (2.0 equiv)
Ag2CO3 (2.0 equiv)
Ag2CO3 (2.0 equiv)
Ag2CO3 (2.0 equiv)
Ag2CO3 (1.0 equiv)
a Reaction conditions: 1a (0.1 mmol), Me3SiCF3 (5.0 equiv), KF (3.0 equiv), DMF (2.5 ml), N2, r.t., 6.5 h. Phenylpropiolic acid was introduced slowly via
syringe pump over four hours. phen=1,10-phenanthroline.
b Yields were as determined by GC analysis, using n-dodecane as internal standard.
c Phenylpropiolicacid was mixed with other raw materials at one pot.
dMe3SiCF3 (3.0 equiv).
Ag2CO3 was better than air, O2 and Cu(OAc)2 (Table 1, Entries 9-
11). When the amount of Me3SiCF3 was reduced to 3.0
equivalents, only 20% yield of 2a was obtained (Table 1, Entry
12). Decreasing the amount of CuI/phen or Ag2CO3 resulted in
lowering yields of 2a respectively (Table 1, Entries 13-15).
2. Results and discussion
Initially,
Cu(I)/Ag(I)
mediated
decarboxylative
trifluoromethylation of phenylpropiolic acid (1a) with Me3SiCF3
in DMF to give the corresponding trifluoromethylated product 2a
was employed as a model reaction (Table 1). When a mixture of
1a (0.1 mmol), Me3SiCF3 (5.0 equiv), KF (3.0 equiv), Ag2CO3
(2.0 equiv), and CuI/phen (1.0 equiv) in DMF was reacting at 70℃
for 24 h under nitrogen atmosphere, 2a was formed in 33% yield
(Table 1, Entry 1), and the homocoupling byproduct
diphenylacetylene was obtained in high yield (50%).When the
reaction was carried out at room temperature, the yield of 2a was
almost the same as that at 70℃ (Table 1, Entry 2). We speculated
that the rate of decarboxylative homocoupling was much faster
than that of trifluoromethylation, the high concentration of
phenylpropiolic acid lead to high yield of byproduct
diphenylacetylene. In order to inhibit the homocoupling
byproduct, we used a syringe pump to introduce 1a in droplet
over a period of 4 h to the mixture of Me3SiCF3, KF, Ag2CO3,
and CuI/phen in DMF at room temperature under N2 atmosphere.
To our delight, the yield of 2a was improved to 89% as
determined by GC analysis (Table 1, Entry 3). Subsequently we
explored the effects of other reagents on this reaction. CuI as a
catalyst showed more efficient than CuBr and CuCl (Table 1,
Entries 4 and 5), whereas Cu(OAc)2 gave poor performance
(Table 1, Entry 6). Screening other ligands, 2,2’-bipyridine (Bpy),
N,N,N’,N’-tetramethylethylenediamine (TMEDA) showed poor
results (Table 1, Entries 7 and 8). Moreover, for the oxidants,
With the optimal reaction conditions in hand, we next
investigated the substrate scope of decarboxylative
trifluoromethylation of arylpropiolic acids (Table 2). Many
functional groups, such as alkoxy, ester, nitro, acetyl, halogen,
could be well-tolerated under the optimal conditions.
Arylpropiolic acids bearing electron-donating groups (phenyl,
butoxy, tert-butyl, methoxyl) at either para- or ortho-positions
proceeded with Me3SiCF3 smoothly to give the corresponding
products in modest to good yields (Table 2, 2b-e, 60%-80%).
Reaction of arylpropiolic acids that bearing two electron-
donating groups such as 3,5-dimethoxy also gave 58% yield of 2f.
Arylpropiolic acids bearing electron-withdrawing groups (acetyl,
cyan, nitryl ) at either para- or ortho- position, gave relatively
low yields of desired products (Table 2, 2h-j, 40%-54%).
Noteworthy is that ester group at para-position was well
compatible with the screening condition (Table 2, 2g, 73%).
Reactions of the halogen-substituted phenylpropiolic acids, such
as 3-bromo, 4-bromo and 4-chloro, could result in a drop in
reaction yields (2m 53%, 2k 31% and 2l 40%) respectively.
Naphthylpropiolic acid gave a fair yield (Table 2, 2n, 51%).
Gratifyingly,
for
the
N-heterocyclic
aromatics,
the
quinolylpropiolic acid also carried out in a good yield of 61%

ACCEPTED MANUSCRIPT
3
3. Conclusions
(Table 2, 2o). In addition, alkylpropiolic acid-6-phenylhex-2-
ynoic acid could also be compatible with this system and
In summary, we have developed a new and effective method
for the construction of a Csp-CF3 bond via a Cu(I)/Ag(I)
mediated decarboxylative trifluoromethylation of arylpropiolic
acids with Me3SiCF3 under relatively mild conditions. This
method tolerates a variety of functional groups and provides a
direct route to produce various trifluoromethylated alkynes. Since
both the salts of carboxylic acids and Me3SiCF3 are easily
Table 2.Decarboxylativetrifluoromethylation of arylpropiolic
available,
this
room
temperature
decarboxylative
trifluoromethylation method will have great advantages
for academic and industrial research.
4. Experimental Section
4.1. General procedures
All reagents were obtained from commercial sources (>99%)
and used without further purification unless otherwise noted.
Anhydrous potassium fluoride (KF) was dried in a vacuum-oven
at 200 ℃ for 24 h and stored in a N2 filled glove box. Anhydrous
N,N’- dimethylformamide (DMF) was dispensed from a solvent
purification system. Analytical thin layer chromatography (TLC)
was carried out with silica gel GF254 precoated plates.
Visualization was accomplished with a UV lamp. The reactions
were carried out under nitrogen atmosphere and the products
were isolated by column chromatography on silica gel (200-300
mesh) using dichloromethane / petroleum ether (PE, 30-60℃)
1
(v/v, 0-1/2). All compounds were characterized by H NMR, 13C
a
Reaction conditions: arylpropiolic acid (0.4 mmol), Me3SiCF3(2.0
1
NMR, 19F NMR and Mass spectrometry. H NMR spectra were
mmol), CuI (0.4 mmol), phen (0.4 mmol), Ag2CO3(0.8 mmol), KF (1.2
mmol), DMF (6.0 mL), N2, rt, 6.5 h, isolated yields.
recorded on Varian INOVA 400M and Bruker 500M instruments.
13C NMR and 19F NMR spectra were recorded on a Bruker 500M
instruments. Chemical shifts (δ) are reported in ppm with TMS as
internal standard. Gas chromatography analyses were performed
with an FID detector. GC-MS data was also performed.
b
Yield of 2a was determined by the 19F NMR with phenyl
trifluoromethyl sulfide as an internal standard.
c Isolated yield of 0.2 mmol 2b.
obtained the moderate yield (Table 2, 2p, 48%).
Based on the previous work,6,12d,g,15,16 a plausible mechanism
for the decarboxylative trifluoromethylation of arylpropiolicacids
with Me3SiCF3 was proposed. As shown in Scheme 2, a complex
[(phen)CuI] A would be generated when the reaction started with
CuI and phen in DMF. The generation of trifluoromethyl anion
could then follow to form the key CuCF3intermediate B.
Subsequent the transmetalation between alkynyl metal-silver
species D and B occurred to form E in the presence of Ag2CO3.
The complex D might be generated from decarboxylation of
silver carboxylates C. Finally, the reductive elimination of
complex E delivered the target compound.
4.1. General procedure for synthesis of arylpropiolic acids
Compounds( 1b-1o)were prepared according to literature.17 To
a mixture of Pd(PPh3)2Cl2 (70 mg, 2 mol %), CuI (38 mg, 4
mol %) and DMF (7 mL) taken in a flask, aryl iodide (5.0 mmol),
propiolic acid (414 mg, 6.0 mmol) and diisopropylamine (1.30 g,
12.5 mmol) were added in that sequence under nitrogen
atmosphere. After stirring the reaction mixture at room
temperature for 5 h, the resulting mixture was diluted with ethyl
acetate, filtered through celite bed, the filtrate was washed with
cold aqueous KOH solution (1 × 100 mL) and acidified with
dilute sulfuric acid (10% solution) at 0 ℃. The solid obtained
was extracted with dichloromethane and the extract was washed
with water, brine solution and dried over anhydrous sodium
sulfate. The organic layer was concentrated in vacuum at 40 ℃,
dried to get the arylpropiolic acids.
D
N
N
Ag
Cu
Cu I
CF3
CO2
N
N
CF3
Ar
A
B
Ag(I)
trans-
metalation
KF
Me3SiCF3
Ag(0)
CO2Ag
4.2. General
procedure
for
Cu(I)/Ag(I)-mediated
CF3
N
decarboxylative trifluoromethylation of arylpropiolic acids
with Ruppert–Prakash reagent (0.4 mmol Scale)
Ar
Ar
CF3
Cu
Ag
C
reductive
elimination
N
E
Ar
CO2
Ar
A mixture of CuI (76 mg, 0.4 mmol), phen (79 mg, 0.4 mmol),
Ag2CO3 (220 mg, 0.8 mmol), KF (69 mg, 1.2 mmol) and DMF (6
mL) was added to a 25mL round-bottom flask that was equipped
with a magnetic stir bar at room temperature in a glove box. The
round-bottom flask was sealed with a rubber plug and taken out.
Then the flask was evacuated and refilled with nitrogen for three
times. Next, Me3SiCF3 (294 µL, 2.0 mmol) was added to the
mixture dropwise in five minutes and the mixture was stirred at
room temperature for 30 minutes. A solution of arylpropiolic
acids (0.4 mmol) in 1.0 mL DMF was added to the flask during 4
h by using a syringe pump at room temperature. After the
addition, the reaction mixture was kept for another 2 h at room
Scheme 2. Plausible mechanism for decarboxylative trifluoromethylation
of arylpropiolic acids
Scheme 2. Plausible mechanism for decarboxylative trifluoromethylation
of arylpropiolic acids

ACCEPTED MANUSCRIPT
4
Tetrahedron
temperature. At the end of reaction, dichloromethane (DCM)
4.3.8 4-(3,3,3-trifluoroprop-1-yn-1-yl)benzonitrile (2i):Yellow
1
was added to the reaction system. The organic layer was
separated and washed with water three times. The combined
organic extracts was dried over Na2SO4 for 2h and then
concentrated under vacuum. After evaporation, the residue was
purified by silica gel column chromatography with petroleum
ether to provide pure desired products.
solid (42 mg, 54% yield). H NMR (400 MHz, CDCl3) δ 7.73 –
7.69 (d, J = 8.5 Hz, 2H), 7.67 (d, J = 8.5 Hz, 2H).13C NMR (126
MHz, CDCl3) δ 131.99 (q, J = 1.3 Hz), 131.31, 122.14, 116.55,
113.43 (q, J = 258.3 Hz), 113.61, 83.00 (q, J = 6.5 Hz),77.88(q, J
= 54.2 Hz). 19F NMR (470 MHz, CDCl3) δ -50.52 (s, 3F).GC-MS
(EI): m/z 195 (M+).
4.3.1 4-(3,3,3-Trifluoroprop-1-yn-1-yl)-1,10-biphenyl (2b):White
4.3.9
1-Nitro-2-(3,3,3-trifluoroprop-1-yn-1-yl)benzene
1
solid (39 mg, 80% yield). H NMR (500 MHz, CDCl3) δ 7.65 –
(2j):Brown solid (43 mg, 50% yield). 1H NMR (500 MHz, CDCl3)
δ 8.12 (d, J = 8.1 Hz, 1H), 7.83-7.62 (m, 3H).13C NMR (126
MHz, CDCl3) δ 149.83, 135.66, 133.50, 131.63, 125.15, 114.51
(q, J = 258.4 Hz), 114.14, 81.60 (q, J = 53.4 Hz), 81.54 (q, J =
6.7 Hz).19F NMR (470 MHz, CDCl3) δ -50.73 (s, 3F).GC-MS
(EI): m/z 215 (M+).
7.59 (m, 6H), 7.51 – 7.46 (m, 2H), 7.45 – 7.39 (m, 1H).13C NMR
(126 MHz, CDCl3) δ 143.73, 139.70, 132.90 (q, J = 1.5 Hz),
129.01, 128.25, 127.30, 127.15, 117.22 (d, J = 1.8 Hz), 114.94(q,
J = 257.0 Hz), 86.56 (q, J = 6.4 Hz), 76.23 (q, J = 52.7 Hz). 19F
NMR (470 MHz, CDCl3) δ -49.67 (s, 3F). GC-MS (EI): m/z =
246 (M+).
4.3.10 1-Bromo-4-(3,3,3-trifluoroprop-1-yn-1-yl)benzene (2k):
1
4.3.2
1-Butoxy-4-(3,3,3-trifluoroprop-1-ynyl)benzene
Yellow oil (31 mg, 31% yield). H NMR (400 MHz, CDCl3) δ
1
(2c):Colorless oil (65 mg, 67% yield ). H NMR (500 MHz,
CDCl3) δ 7.46 (d, J = 8.5 Hz, 2H), 6.86 (d, J = 8.5 Hz, 2H), 3.97
(t, J = 6.4 Hz, 2H), 1.80 – 1.73 (m, 2H), 1.55 – 1.44 (m, 2H),
0.97 (t, J = 7.4 Hz, 3H).13C NMR (126 MHz, CDCl3) δ 161.21,
134.12 (q, J= 1.3 Hz), 115.12(q, J = 257.0 Hz) , 114.79, 110.02
(q, J = 1.7 Hz), 87.23 (q, J = 6.4 Hz), 73.73 (q, J = 51.7 Hz),
67.92, 31.12, 19.17, 13.74. 19F NMR (470 MHz, CDCl3) δ -49.38
(s, 3F).GC-MS (EI): m/z 242 (M+).
7.54 (d, J = 8.4 Hz, 2H), 7.41 (d, J = 8.4 Hz, 2H).13C NMR (126
MHz, CDCl3) δ 133.75, 132.08, 125.73, 117.41 (q, J = 1.8 Hz),
114.72 (q, J = 257.0 Hz), 85.37 (q, J = 6.5 Hz) . 19F NMR (470
MHz, CDCl3) δ -50.06 (s, 3F).GC-MS (EI): m/z 248 (M+).
4.3.11 1-Chloro-4-(3,3,3-trifluoroprop-1-yn-1-yl)benzene (2l):
Yellow solid (33 mg, 40% yield). 1H NMR (500 MHz, CDCl3) δ
7.49 (d, J = 8.6 Hz, 2H), 7.38 (d, J = 8.6 Hz, 2H).13C NMR (126
MHz, CDCl3) δ137.37 (s), 133.65 (d, J = 1.5 Hz), 129.15 (s),
116.94 (d, J = 1.8 Hz), 114.71 (q, J = 257.0 Hz), 85.31 (q, J = 6.4
Hz), 85.31 (q, J = 6.4 Hz), 76.65(q, J = 53.1 Hz). 19F NMR (470
MHz, CDCl3) δ -50.01 (s, 3F). GC-MS (EI): m/z 204 (M+).
4.3.3
1-tert-butylphenyl-4-(3,3,3-trifluoroprop-1-ynyl)benzene
(2d):Yellow solid (60 mg, 66% yield). 1H NMR (500 MHz,
CDCl3) δ7.48 (d, J = 8.3 Hz, 2H), 7.40 (d, J = 8.3 Hz, 2H), 1.32
(s, 9H).13C NMR (126 MHz, CDCl3) δ 154.55 (s), 132.25 (q, J =
1.4 Hz), 125.69, 116.00, 115.44 (q, J = 1.8 Hz), 113.96, 86.93 (q,
J = 6.4 Hz), 75.22(q, J = 52.5 Hz) , 35.04, 31.01. 19F NMR (470
MHz, CDCl3) δ -49.57 (s, 3F). GC-MS (EI): m/z 226 (M+)..
4.3.12 1-Bromo-3-(3,3,3-trifluoroprop-1-yn-1-yl)benzene (2m):
Yellow oil (66 mg, 53% yield). H NMR (500 MHz, CDCl3) δ
1
7.70 (s, 1H), 7.61 (d, J = 8.1 Hz, 1H), 7.49 (d, J = 7.7 Hz, 1H),
7.27 (t, J = 7.9 Hz, 1H).13C NMR (126 MHz, CDCl3) δ 135.09 (q,
J = 1.5 Hz), 134.14, 130.96 (q, J = 1.4 Hz), 130.11, 122.46,
120.44 (q, J = 1.8 Hz), 114.62 (q, J = 258.3 Hz), 84.63 (q, J = 6.5
Hz),76.66(q, J = 53.0 Hz) . 19F NMR (470 MHz, CDCl3) δ -50.16
(s, 3F). GC-MS (EI): m/z 248 (M+).
4.3.4 1-Methoxy-2-(3,3,3-trifluoroprop-1-ynyl)benzene (2e):
1
Yellow oil (48 mg, 60% yield). H NMR (400 MHz, CDCl3) δ
7.54 – 7.42 (m, 2H), 7.01 – 6.90 (m, 2H), 3.92 (s, 3H). 13C NMR
(126 MHz, CDCl3) δ 160.30, 133.34 (q, J = 1.3 Hz), 131.47,
119.51, 114.03 (q, J = 257.0 Hz), 113.32, 82.76 (q, J = 6.4 Hz),
78.32 (q, J = 51.7 Hz). 19F NMR (470 MHz, CDCl3) δ -49.45 (s,
3F). GC-MS (EI): m/z 220 (M+).
4.3.13 1-(3,3,3-trifluoroprop-1-yn-1-yl)naphthalene (2n): Yellow
oil (45 mg, 51% yield). 1H NMR (500 MHz, CDCl3) δ 8.19 (d, J
= 8.3 Hz, 1H), 7.93 (d, J = 8.3 Hz, 1H), 7.86 (d, J = 8.1 Hz, 1H),
7.78 (d, J = 7.2 Hz, 1H), 7.65 – 7.58 (m, 1H), 7.58 – 7.52 (m,
1H), 7.44 (dd, J = 10.6, 4.8 Hz, 1H).13C NMR (126 MHz, CDCl3)
δ 133.16 (q, J = 0.8 Hz), 132.99, 132.52 (q, J = 1.8 Hz), 131.53,
128.59, 127.82, 127.03, 125.30, 124.98, 115.98 (q, J = 1.76 Hz),
115.10 (q, J = 258.3 Hz), 85.20 (q, J = 6.4 Hz), 80.18 (q, J = 52.9
Hz). 19F NMR (470 MHz, CDCl3) δ -49.42 (s, 3F). GC-MS (EI):
m/z 220 (M+).
4.3.5 1,3-dimethoxy-5-(3,3,3-trifluoroprop-1-ynyl)benzene (2f):
1
Yellow oil (54 mg, 58% yield). H NMR (500 MHz, CDCl3) δ
6.61 (d, J = 2.3 Hz, 2H), 6.48 (t, J = 2.3 Hz, 1H), 3.72 (s, 6H).13C
NMR (126 MHz, CDCl3) δ 160.70, 119.64 (q, J = 1.8 Hz),
114.78(q, J = 257.4 Hz), 110.11, 104.19, 86.50 (q, J = 6.4 Hz),
75.00 (q, J = 52.8 Hz), 55.49. 19F NMR (470 MHz, CDCl3) δ -
49.84 (s, 3F). GC-MS (EI): m/z 230 (M+).
4.3.6 Ethyl -4-(3,3,3-trifluoroprop-1-yn-1-yl)benzoate (2g):
Colorless oil (71 mg, 73% yield). H NMR (500 MHz, CDCl3) δ
4.3.14 3-(3,3,3-trifluoroprop-1-yn-1-yl)quinoline (2o): Yellow
solid (54mg, 61%yield). H NMR (500 MHz, CDCl3) δ 8.86 (s,
1
1
8.07 (d, J = 8.3 Hz, 2H), 7.63 (d, J = 8.3 Hz, 2H), 4.40 (q, J = 7.1
Hz, 2H), 1.41 (t, J = 7.1 Hz, 3H).13C NMR (126 MHz, CDCl3) δ
164.43, 131.50, 131.38(q, J = 1.3 Hz), 128.65, 121.71 (q, J = 1.8
Hz), 113.64 (q, J = 258.3 Hz), 84.34 (q, J = 6.5 Hz), 76.68(q, J =
53.0 Hz), 60.50, 13.23. 19F NMR (470 MHz, CDCl3) δ -50.22 (s,
3F). GC-MS (EI): m/z 242 (M+).
1H), 8.29 (s, 1H), 8.04 (d, J = 8.8 Hz, 1H), 7.71 (t, J = 7.6 Hz,
2H), 7.53 (t, J = 7.5 Hz, 1H).13C NMR (126 MHz, CDCl3) δ
151.11, 147.93, 140.81 (q, J = 1.4 Hz), 131.65 (s), 129.64,
127.95, 127.92, 126.53, 115.65 (q, J = 257.0 Hz), 112.59 (q, J =
1.6 Hz), 83.87 (q, J = 6.4 Hz), 78.48 (q, J = 51.7 Hz). 19F NMR
(470 MHz, CDCl3) δ -50.11(s, 3F). GC-MS (EI): m/z 221 (M+).
4.3.7
1-Acetyl--4-(3,3,3-trifluoroprop-1-ynyl)benzene
(2h):
Acknowledgments
1
White solid (34 mg, 40% yield). H NMR (500 MHz, CDCl3) δ
7.98 (d, J = 8.4 Hz, 2H), 7.66 (d, J = 8.4 Hz, 2H), 2.63 (s,
3H).13C NMR (126 MHz, CDCl3) δ 196.91, 138.38, 132.69 (q, J
= 1.0 Hz), 128.35, 122.92 (d, J = 1.6 Hz), 114.60(q, J = 258.3
Hz), 85.17 (q, J = 6.4 Hz), 77.93(q, J = 53.0 Hz), 77.72, 77.28,
26.69. 19F NMR (470 MHz, CDCl3) δ -50.23 (s, 3F).GC-MS (EI):
m/z 212 (M+).
This work was supported by the National Natural Science
Foundation of China (NSFC) (Project No 21176039 and
20923006)
References and notes
1 (a) Schlosser, M. Angew. Chem., Int. Ed. 2006, 45, 5432-5446; (b)
Muller, K.; Faeh, C.;Diederich, F. Science. 2007, 317, 1881-1886.

ACCEPTED MANUSCRIPT
5
2 (a) Kirsch, P. Wiley-VCH: Weinheim, 2004; (b) Isanbor C, O’Hagan
D. J Fluorine Chem, 2006, 127, 303-319.
11 (a) Park, K.; Bae, G.; Park, A.; Kim, Y.; Choe, J.; Song, K. H.; Lee,
S.,Tetrahedron Letters. 2011, 52, 576-580; (b) Park, K.; Bae, G.;
Moon, J.; Choe, J.; Song, K. H.; Lee, S., J. Org. Chem .2010, 75,
6244-51; (c) Moon, J.; Jeong, M.; Nam, H.; Ju, J.; Moon, J. H.; Jung
H.M.; Lee, S., Org. Lett. 2008, 10,945-948;(d) Choe, J.; Yang, J.;
Park, K.; Palani, T.; Lee, S., Tetrahedron Letters. 2012, 53, 6908-
6912.
12(a) Li, X.; Yang, F.; Wu, Y., J.Org. Chem. 2013, 78, 4543-50; (b) Shi,
L.; Jia, W.; Li, X.; Jiao, N., Tetrahedron Letters. 2013, 54, 1951-
1955; (c) Zhao, D.; Gao, C.; Su, X.; He, Y.; You, J.; Xue, Y., Chem
Commun (Camb). 2010, 46, 9049-51; (d) Feng, C.; Loh, T. P., Chem
Commun (Camb). 2010, 46, 4779-4781; (e) Lu, L.; Chellan, P.; Smith,
G. S.; Zhang, X.; Yan, H.; Mao, J., Tetrahedron. 2014, 70, 5980-
5985; (f) Li, X.; Yang, F.; Wu, Y.; Wu, Y., Org Lett. 2014, 16, 992-5;
(g) Tummanapalli, S; Muthuraman, P; Vangapandu, D. N.;
Shanmugavel, G.; Kambampati, S.; Lee, K. W., RSC Adv. 2015, 5,
49392-49399.
13 (a) Jia, W.; Jiao, N. Org. Lett. 2010, 12, 2000. (b) Hu, J.; Zhao, N.;
Yang, B.; Wang, G.; Guo, L.-N.; Liang,Y.-M.; Yang, S.-D. Chem.,
Eur. J.2011, 17, 5516. (c) Park, J.; Park, E.;Kim, A.; Park, S.-A.; Lee,
Y.; Chi, K.-W.; Jung, Y. H.; Kim, I. S. J. Org.Chem. 2011, 76, 2214.
(d) Ranjit, S.; Duan, Z.; Zhang, P.; Liu, X. Org.Lett. 2010, 12, 4134.
(e) Zhang, W. W.; Zhang,X. G.; Li, J. H. J. Org. Chem. 2010, 75,
5259; (f) Wang, X. N.; Yeom, H. S.; Fang, L. C.; He, S.; Ma, Z. X.;
Kedrowski, B. L.; Hsung, R. P., Acc Chem Res. 2014, 47, 560-78.
14 He, Z., Zhang, R., Hu, M., Li, L., Ni, C., & Hu, J. Chem. Sci. 2013, 4,
3478-3483.
15 (a) M. Oishi, H. Kondo, H. Amii, Chem. Commun. 2009, 1909-
1911;(b) L. Chu, F.-L. Qing, Org. Lett. 2010, 12, 5060-5063;(c)
Morimoto, H.; Tsubogo, T.; Litvinas, N.; Hartwig, J., Angew. Chem.,
Int. Ed. 2011, 123, 3877-3882;(d) Tomashenko, O. A.; Escudero-
Adan, E. C.; Belmonte, M.; Grushin, V. Angew. Chem., Int. Ed. 2011,
50, 7655-7659;(e) Litvinas, N. D.; Fier, P.; Hartwig, J.,Angew. Chem.,
Int. Ed. 2012, 51, 536-539;(f) Gonda, Z.; Kovacs, S.; Weber, C.; Gati,
T.; Meszaros, A.; Kotschy, A.; Novak, Z.,Org Lett. 2014, 16, 4268-
4271.
3 (a) Novak, P.; Lishchynskyi, A.; Grushin, V. V.,J. Am. Chem. Soc.
2012,134, 16167-16170; (b) Xu, J.; Xiao, B.; Xie, C. Q.; Luo, D. F.;
Liu, L.; Fu, Y.,Angew. Chem., Int. Ed. 2012, 124, 12719-12722; (c)
Xu, J.; Xiao, B.; Xie, C.-Q.; Luo, D.-F.; Liu, L.; Fu, Y., Angew.
Chem., Int. Ed. 2012, 51, 1-5; (d) Noritake, S.; Shibata, N.;
Nakamura, S.; Toru, T.; Shiro, M.,Eur. J. Org. Chem. 2008, 20,
3465-3468.
4 (a) Kawai, H.; Furukawa, T.; Nomura, Y.; Tokunaga, E.; Shibata,
N.,Org. Lett. 2011, 13, 3596-3599; (b) Prakash, G. K. S.; Parag, V. J.;
Batamack, P. T. C.; Olah, G. A., Science. 2012, 338, 1324-1327; (c)
Wu, X.; Chu, L.; Qing, F.-L. Angew. Chem., Int. Ed. 2013, 125,
2254-2258; (d) Deb, A.; Manna, S.; Modak, A.; Patra, T.; Maity, S.;
Maiti, D., Angew. Chem., Int. Ed. 2013, 125, 9929-9932; (e) Ji, Y. L.,
Luo, J. J., Lin, J. H., Xiao, J. C.Org. Lett. 2016, 18, 1000-1003.
5 (a) He, Z.; Lou, T.; Hu, M.; Cao, Y.; Hu, J.,Angew. Chem., Int. Ed.
2012, 51, 3944-3947; (b) Xu, P.; Abdukader, A.; Hu, K.; Cheng, Y.;
Zhu, C.,Chem.Commun. 2014, 50, 2308-2310; (c) Li, Z.; Cui, Z.; Liu,
Z.-Q. Org. Lett. 2013, 15, 406-409; (d) Liu, T.; Shen, Q. Org. Lett.
2011, 13, 2342-2345; (e) Yasu, Y.; Kioke, T.; Akita, M.,Chem.
Commun. 2013, 49, 2037-2039;(f)Prakash, G. K. S.; Krishnan, H. S.;
Jog, P. V.; Iyer, A. P.; Olah, G. A.,Org. Lett.2012,14, 1146-1149.(g)
Iqbal, N.; Jung, J.; Park, S.; Cho, E. J, Angew. Chem., Int. Ed.2014,
53, 539-542.
6 (a) Chu, L.; Qing, F.-L,J. Am. Chem. Soc. 2010, 132, 7262-7263; (b)
Zhang, K.; Qiu, X.; Huang, Y.; Qing, F.-L,Eur.J. Org. Chem.2012,
58-61; (c) Jiang, X.; Chu, L.; Qing, F.-L,J. Org. Chem. 2012, 77,
1251-1257.
7 (a) Li, X.; Zhao, J.; Zhang, L.; Hu, M.; Wang, L.; Hu, J.,Org Lett.
2015, 17, 298-301;(b) Luo, D.-F.; Xu, J.; Fu, Y.; Guo, Q.-
X,Tetrahedron. 2012, 53, 2769-2772; (c) Weng, Z.; Li, H.; He, W.;
Yao, L.-F.; Tan, J.; Chen, J.; Yuan, Y.; Huang, K.-W,Tetrahedron
Letters. 2012, 68, 2527-2531.(d) Zheng, H.; Huang, Y.; Wang, Z.; Li,
H.; Huang, K.-W.; Yuan, Y.; Weng, Z., Tetrahedron. 2012, 53, 6646-
6649.
8 Kolarovič, A., Schnürch, M., &Mihovilovic, M. D. J. Org. Chem.
2011, 76, 2613-2618.
16 Rodriguez, N.; Goossen, L. J., Chemical Society Reviews. 2011, 40,
5030-48.
9 Li, X.; Yang, F.; Wu, Y.; Wu, Y., Org Lett. 2014, 16, 992-5.
10 (a) Park, K.; You, J.-M.; Jeon, S.; Lee, S. Eur. J. Org. Chem.
2013,1973−1978;(b) Park, K.; Palani, T.; Pyo, A.; Lee, S.
Tetrahedron Lett. 2012, 53, 733−737;(c) Park, K.; Lee, S.,RSC
Advances. 2013, 3, 14165; (d) Hwang, J.; Park, K.; Choe, J.; Min, H.;
Song, K. H.; Lee, S., J. Org. Chem. 2014, 79, 3267-71; (e) Park, K.;
You, J.-M.; Jeon, S.; Lee, S. Eur. J. Org. Chem. 2013,1973−1978. (f)
Park, K.; Palani, T.; Pyo, A.; Lee, S. Tetrahedron Lett. 2012, 53,
733−737.
17 Ponpandian, T.; Muthusubramanian, S., Tetrahedron Letters. 2012,
53, 4248-4252.
Click here to remove instruction text...