Mild copper-catalyzed trifluoromethylation of terminal alkynes using an electrophilic trifluoromethylating reagent

Article abstract of DOI:10.1016/j.tet.2011.12.085

A catalytic process for trifluoromethylation of terminal alkynes with Togni's reagent has been developed, affording trifluoromethylated acetylenes in good to excellent yields. The reaction is conducted at room temperature and exhibits tolerance to a range

Full text of DOI:10.1016/j.tet.2011.12.085

Tetrahedron 68 (2012) 2527e2531
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Mild copper-catalyzed trifluoromethylation of terminal alkynes using
an electrophilic trifluoromethylating reagent
, ,
Zhiqiang Weng a y, Huaifeng Li b, Weiming He a, Liang-Feng Yao b, Jianwei Tan a, Jinfa Chen a,
*
,
Yaofeng Yuan a, Kuo-Wei Huang b
*
a Department of Chemistry, Fuzhou University, Fujian 350108, China
b KAUST Catalysis Centre and Division of Chemicals and Life Sciences and Engineering, King Abdullah University of Science and Technology, Thuwal 23955-6900, Saudi Arabia
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 31 August 2011
Received in revised form 22 December 2011
Accepted 30 December 2011
Available online 4 January 2012
A catalytic process for trifluoromethylation of terminal alkynes with Togni’s reagent has been developed,
affording trifluoromethylated acetylenes in good to excellent yields. The reaction is conducted at room
temperature and exhibits tolerance to a range of functional groups.
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
Copper catalyst
Terminal alkyne
Trifluoromethylation reaction
1. Introduction
pharmaceuticals and the preparation of functional materials.12
General methods for the preparation of trifluoromethylated acet-
The incorporation of trifluoromethyl groups (eCF3) into organic
structures could dramatically improve their physical, chemical and
biological properties, such as metabolic stability and lipophilicity.1
Many biological active pharmaceuticals and agrochemicals contain
CF3 group(s) as the indispensable moiety.1,2 As a consequence, the
development of new methodologies for the introduction of tri-
fluoromethyl group into organic molecules has received much at-
tention.3,4 Among various methods for the synthesis of
ylenes include the treatment of trifluoropropynyl metal reagents
with aryl iodides,13 dehalogenation of trifluoromethylethenes,14
electrophilic trifluoromethylation of alkynyl lithium reagent15 or
trifluoromethylation of stannylacetylenes.16 While direct tri-
fluoromethylation of sp CeH bonds represents a straightforward
and convenient approach for the synthesis of trifluoromethylated
acetylenes, available routes are limited. Only recently, Chu and Qing
reported a remarkable copper-mediated protocol for the cross-
coupling reaction of terminal alkynes with ‘CuCF3’ generated in
situ from TMSCF3, KF and Cu.17 This reaction, however, requires the
use of stoichiometric amount of copper reagents, a high reaction
temperature (100 ꢀC) and excess amounts of trifluoromethylating
reagent (5 equiv).17 The development of a mild and catalytic ap-
proach for the synthesis of trifluoromethylated acetylenes is still
highly desirable. Herein, we report an efficient copper-catalyzed
room temperature trifluoromethylation of terminal alkynes.
trifluoromethylated
compounds,
metal-catalyzed
tri-
fluoromethylation reactions are particularly important and
desirable.5e8 A number of examples have been demonstrated in the
literature for the Pd- or Cu-catalyzed trifluoromethylation of aryl
halides, indoles, aryl or vinyl boronic acids and aryl CeH bonds,
using either the nucleophilic or electrophilic trifluoromethylating
reagents, such as RuppertePrakash’s reagent (TMSCF3)5 or its ethyl
derivative,6 Togni’s reagent,7 Umemoto’s reagent8 and potassium
(trifluoromethyl)trimethoxyborate9 as CF3 sources. While consid-
erable progress has been made towards the development of tri-
fluoromethylation reactions, catalytic methods for the introduction
of CF3 groups into organic compounds are still challegning.3e,10,11
Trifluoromethylated acetylenes are a class of useful compounds
due to their applications as building blocks for the synthesis of
2. Results and discussion
Our initial studies focused on the trifluoromethylation of phe-
nylacetylene (1a) in the presence of copper(I) iodide with various
ligands and electrophilic trifluoromethylating reagents (Table 1). A
catalytic amount of CuI (20 mol %) and 1,10-phenanthroline L1
(40 mol %) gave a poor but encouraging yield of 43% from a mixture
of 1a, Togni’s reagent (1.5 equiv) and K2CO3 (2.0 equiv) in CH2Cl2 at
room temperature (Table 1, entry 1). Further analysis of the
* Corresponding authors. E-mail addresses: zweng@fzu.edu.cn (Z. Weng), hkw@
kaust.edu.sa (K.-W. Huang).
y
Tel.: þ86 59122866121; fax: þ86 59122866161.
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.12.085

2528
Z. Weng et al. / Tetrahedron 68 (2012) 2527e2531
Table 1
Table 2
CuI-catalyzed trifluoromethylation of 1a with electrophilic trifluoromethylating
Optimization of base and solvent for the CuI/L1-catalyzed trifluoromethylation
reagentsa
of 1aa
Entry
1d
2
3
4
5
6
7
CFþ3 reagent
Ligand
Yield of 2ab,c (%)
Entry
Base
Solvent
Yield of 2ab (%)
3a
3a
3a
3a
3a
3b
3c
L1
L1
L2
L3
L4
L1
L1
43 (51)
75
60
65
50
1
2
3
4
5
6
K2CO3
Cs2CO3
KHCO3
NaOAc
KF
CH2CI2
CH2CI2
CH2CI2
CH2CI2
CH2CI2
CH2CI2
CH2CI2
CH2CI2
DCE
DMF
DMAC
NMP
CH3CN
DMSO
Hexane
Toluene
CH3OH
Ethylene glycol
1,4-Dioxane
THF
75
46
78
46
71
73
68
<1
43
60
68
52
28
33
<1
<1
6
<1
<1
K3PO4
Et3N
7
8c
9
KHCO3
KHCO3
KHCO3
KHCO3
KHCO3
KHCO3
KHCO3
KHCO3
KHCO3
KHCO3
KHCO3
KHCO3
KHCO3
KHCO3
KHCO3
10
11
12
13
14
15
16
17
18
19
20
21
22
<1
<1
<1
<1
<1
Diglyme
Et2O
a
Reaction conditions: 1a (0.20 mmol),
3 (0.3 mmol), CuI (20 mol %), ligand
a
Reaction conditions: 1a (0.20 mmol), Togni’s reagent (0.3 mmol), CuI (20 mol %),
phen (40 mol %) and base (0.4 mmol) in solvent (3 mL), rt, 24 h. Compound 1a was
added to the reaction mixture over a 6 h period by using a syringe pump.
(40 mol %) and K2CO3 (0.4 mmol) in CH2Cl2 (3 mL), rt, 24 h. Compound 1a was added
to the reaction mixture over a 6 h period by using a syringe pump.
b
The yields of 2a were determined by 19F NMR analysis of the crude reaction
b
Yields were determined by 19F NMR analysis of the crude reaction mixture with
mixture with an internal standard.
c
an internal standard.
GC yield of byproduct is in parentheses.
Compound 1a was added in a single aliquot.
c
d
Without Cu catalyst.
reaction yields (Table 2, entries 10e14). Running the reaction in
polar protic solvent (CH3OH) only afforded a small amount of de-
sired product 2a (Table 2, entry 17). Ether-type solvents did not
provide any detectable trifluoromethylation product under the
same reaction conditions (Table 2, entries 18e22).
byproducts revealed that the undesired homocoupling diyne was
also obtained in 51% yield (Table 1, entry 1). With the aim of re-
ducing the byproduct formation, slow addition of 1a to a mixture of
the rest of reagents in CH2Cl2 using a syringe pump over a period of
6 h significantly improved the yield of the desired product 2a in
75% (Table 1, entry 2). It was found that other chelating amine li-
gands, such as 3,4,7,8-tetramethyl-1,10-phenanthroline L2, 4,7-
diphenyl-1,10-phenanthroline L3, or 2,9-dimethyl-4,7-diphenyl-
1,10-phenanthroline L4 showed lower reactivities compared to that
of L1 (Table 1, entries 3e5). Sequential examinations on other
electrophilic trifluoromethylating reagents indicated that only
a trace amount of desired product 2a could be obtained when 5-
(trifluoromethyl)-dibenzothiophenium trifluoromethanesulfonate
3b and 5-(Trifluoromethyl)-dibenzothiophenium tetrafluoroborate
3c was used (Table 1, entries 6 and 7).
The effect of bases and solvents on the direct tri-
fluoromethylation of 1a with 3a was also studied, as summarized in
Table 2. Among all the tested bases, KHCO3 provided the most
optimal yield of 78% (Table 2, entry 3). It was found that bases, such
as Cs2CO3 and NaOAc were less effective that KHCO3 (Table 2, en-
tries 2 and 4). When KF, K3PO4 and Et3N were employed, compa-
rable yields to KHCO3 were obtained (Table 2, entries 5e7). The
presence of copper catalyst was proven to be essential for this re-
action to proceed as no detectable product was observed when
performing the reaction in the absence of the copper catalyst (Table
2, entry 8). Interestingly, the choice of solvent has a great effect on
the reaction yield. Evaluations of various organic solvents in the
presence of KHCO3 as base revealed that CH2Cl2 provided the best
yield, while this reaction failed to proceed in hexane or toluene
(Table 2, entries 3, 15 and 16). Polar aprotic solvents, such as DMF,
DMAC, NMP, CH3CN and DMSO did not effectively improve the
With these optimized conditions in hand, we proceeded to in-
vestigate the substrate scope with various alkynes (Table 3). The 4-
alkyl-substituted phenylacetylene smoothly underwent the tri-
fluoromethylation reaction with Togni’s reagent to afford tri-
fluoromethylated products in 70e98% yield (Table 3, entries 1 and
3e5). The polycyclicaromatic, 9-ethynylphenanthrene was then
employed as substrate, giving the corresponding product in good
yield up to 91% (Table 3, entry 6). The high reactivity was also ob-
served with substrates bearing electron-donating groups (Table 3,
entries 7 and 8). It is notable that the reaction was tolerated with
halide-containing aryl alkynes under the reaction conditions (Table
3, entries 9 and 10). The amine-substituted aryl alkynes were also
effective and produced the trifluoromethylated compound in 94%
yield (Table 3, entry 11). It should be noted that aliphatic alkynes
(Table 3, entry 12) and heterocycles, such as 2-ethynylthiophene
(Table 3, entry 13), could be employed as substrates to afford the
target products in good yields.
A plausible mechanism for the trifluoromethylation of alkynes
with CFþ3 is depicted in Scheme 1. A di-nitrogen ligated (N,N)CuX
(A) complex would be initially generated in situ by the reaction of
CuI with phen in CH2Cl2. The coordination/deprotonation of the
alkyne could then follow to form a copper(I)-acetylide species B in
the presence of a base. Subsequent oxidative addition of CFþ3 to
species B leads to the formation of a Cu(alkynyl)(trifluoromethyl)
complex C. Finally, product reductive elimination furnishes the
trifluoromethylated alkyne and regenerates the starting copper
complex A to complete the catalytic cycle.

Z. Weng et al. / Tetrahedron 68 (2012) 2527e2531
2529
Table 3
Copper-catalyzed trifluoromethylation of terminal alkynesa
Entry
1
Substrate
Product
Yieldb (%)
91
2
3
4
5
94
Scheme 1. Mechanistic proposal for copper-catalyzed coupling of terminal alkynes
and CFþ3
74
70
98
.
4. Experimental
4.1. General
All solvents were purified by standard method. 1H NMR, 19F
NMR and 13C NMR spectra were recorded using BrukerAVIII 400 or
AVIII 500 spectrometer. 1H NMR and 13C NMR chemical shifts were
reported in parts per million (ppm) downfield from tetrame-
thylsilane and 19F NMR chemical shifts were determined relative
to CFCl3 as outside standard and low field is positive. Coupling
constants (J) are reported in Hertz (Hz). The residual solvent peak
6
91
was used as an internal reference: 1H NMR (chloroform
d 7.26) and
13C NMR (chloroform
d
77.0). The following abbreviations were
7
83
70
71
81
94
used to explain the multiplicities: s¼singlet, d¼doublet, t¼triplet,
q¼quartet, m¼multiplet, br¼broad. All reagents were received
from commercial sources. Solvents were freshly dried and
degassed according to the purification handbook Purification of
Laboratory Chemicals before using. Column chromatography pu-
rifications were performed by flash chromatography using Merck
silica gel 60.
8
9
4.2. General procedure for the copper-catalyzed
trifluoromethylation of terminal alkynes using an
electrophilic trifluoromethylating reagent
10
11
12c
In
a glovebox, CuI (0.04 mmol), Phen(0.08 mmol), base
(0.40 mmol) and electrophilic trifluoromethylating reagent
(0.30 mmol) were added to a Schlenk tube that was equipped with
a stirring bar. Freshly distilled solvent (1.4 mL) was added into this
tube. Terminal alkynes (0.20 mmol) in the same solvent (1.6 mL)
was added into a small vial. Both the tube and the vial were capped
with a septum and taken out. The solution of alkyne was added to
the tube over 6 h by using a syringe pump under Ar atmosphere
(1 atm). After addition, the reaction mixture was kept for another
18 h at room temperature. Aqueous phase was extracted with
CH2Cl2 and the combined organic extracts were dried over anhy-
drous Na2SO4, and concentrated in vacuo. The product was purified
by flash chromatography on silica gel with petroether. NMR yield
was determined by 19F NMR using trifluorobenzene as an internal
standard before working up the reaction.
77
83
13c
a
Reaction conditions: 1 (0.20 mmol), Togni’s reagent (0.3 mmol), CuI (20 mol %),
phen (40 mol %) and KHCO3 (0.4 mmol) in dichloromethane (3 mL), rt, 24 h. Com-
pound 1 was added to the reaction mixture over a 6 h period by using a syringe
pump.
b
Isolated yields.
c
Yields were determined by 19F NMR with an internal standard.
3. Conclusion
In summary, we have developed an effective copper catalyst
system for the trifluoromethylation of terminal alkynes with elec-
trophilic trifluoromethylating reagents. Our catalytic reactions
proceed smoothly at room temperature and can tolerate a variety of
functionalities, such as alkoxyl, amino and halide groups. The de-
velopment of related trifluoromethylation reactions as well as
mechanistic studies are currently underway in our laboratories.
4.2.1. 1-Methyl-4-(3,3,3-trifluoroprop-1-ynyl)benzene
(2b).14b 1H
NMR (500 MHz, CDCl3, 293 K):
d
ppm 7.45 (d, J¼8.1 Hz, 2H), 7.20 (d,
J¼7.9 Hz, 2H), 2.39 (s, 3H). 19F NMR (470 MHz, CDCl3):
ꢁ52.00 (s, 3F). GCeMS m/z 184 (Mþ), 115 (MþꢁCF3).
d ppm
4.2.2. 1-Methyl-3-(3,3,3-trifluoroprop-1-ynyl)benzene
NMR (400 MHz, CDCl3, 293 K): ppm 7.37 (m, 2H), 7.30 (m, 2H),
(2c).18 1H
d

2530
Z. Weng et al. / Tetrahedron 68 (2012) 2527e2531
2.37 (s, 3H). 19F NMR (377 MHz, CDCl3):
d
ppm ꢁ49.7 (s, 3F). 13C
(s), 126.22 (s), 121.20 (s), 113.62 (s), 84.73 (d, J¼6.8 Hz), 79.27 (d,
J¼53.1 Hz). GCeMS m/z 250 (MþþH).
NMR (100.7 MHz, CDCl3):
d ppm 138.71 (s), 133.06 (s), 131.93 (s),
129.68 (s), 128.69 (s), 116.36 (q, J¼256.7 Hz), 86.97 (d, J¼6.8 Hz),
75.50 (d, J¼52.8 Hz), 21.23 (s).
4.2.10. 1-Bromo-4-(3,3,3-trifluoroprop-1-ynyl)benzene (2k).12c 1H
NMR (400 MHz, CDCl3, 293 K):
d
ppm 7.54 (d, J¼8.4 Hz, 2H), 7.40 (d,
4.2.3. 1-Ethyl-4-(3,3,3-trifluoroprop-1-ynyl)benzene (2d). 1H NMR
J¼8.5 Hz,2H).19FNMR(377 MHz,CDCl3):
d
ppmꢁ50.1(s,3F).13CNMR
(500 MHz, CDCl3, 293 K):
d
ppm 7.48 (d, J¼8.1 Hz, 2H), 7.22 (d,
(100.7 MHz, CDCl3): d ppm 133.90 (s),132.23 (s),125.89 (s),117.56 (s),
J¼8.1 Hz, 2H), 2.69 (q, J¼7.6 Hz, 2H), 1.26 (t, J¼7.5 Hz, 3H). 19F NMR
113.61(s), 85.50 (q, J¼6.0 Hz), 76.55 (s). GCeMS m/z 248 (Mþ).
(470 MHz, CDCl3):
d
ppm ꢁ51.78 (s, 3F). 13C NMR (126 MHz, CDCl3):
d
ppm 147.69 (s), 132.48 (q, J¼1.5 Hz), 128.24 (s), 115.65 (s), 113.95
4.2.11. 3-(3,3,3-Trifluoroprop-1-ynyl)aniline (2l). 1H NMR (500 MHz,
(s), 86.98 (q, J¼6.5 Hz), 75.42 (q, J¼52.4 Hz), 28.98 (s), 15.15 (s). IR
CDCl3, 293 K):
6.86 (t, J¼3.8 Hz, 1H), 6.79 (ddd, J¼7.5, 4.6, 2.9 Hz, 1H), 3.90e3.71
(m, 2H). 13C NMR (126 MHz, CDCl3)
146.52 (s), 129.62 (s),
d
ppm 7.19 (t, J¼7.9 Hz, 1H), 6.97 (d, J¼7.6 Hz, 1H),
(KBr):
n 2929, 2874, 2254, 1462, 1380, 1341, 1316, 1264, 1164, 1148,
1026, 908, 862, 728 cmꢁ1. GCeMS m/z 198 (Mþ), 183 (MþꢁCH3).
HRMS (APPI): calculated for C13H19F3O2 (Mþ2MeOHþ2H):
264.13371; found: 264.14825.
d
122.63 (q, J¼1.6 Hz), 118.15 (q, J¼1.5 Hz), 117.63 (s), 115.92 (s), 113.88
(s), 86.95 (q, J¼6.5 Hz), 75.03 (q, J¼52.4 Hz). 19F NMR
(470 MHz, CDCl3):
d
ppm ꢁ51.86 (s, 3F). GCeMS m/z 185 (Mþ), 116
4.2.4. 1-Propyl-4-(3,3,3-trifluoroprop-1-ynyl)benzene
(2e).19 1H
(MþꢁCF3).
NMR (500 MHz, CDCl3, 293 K):
d
ppm 7.47 (d, J¼8.1 Hz, 2H), 7.19 (d,
J¼8.0 Hz, 2H), 2.61 (t, J¼7.5 Hz, 2H), 1.65 (m, 2H), 0.94 (t, 3H). 19F
Acknowledgements
NMR (470 MHz, CDCl3):
d
ppm ꢁ51.77 (s, 3F). 13C NMR (126 MHz,
CDCl3):
d
ppm 146.18 (s), 132.39 (q, J¼1.4 Hz), 128.82 (s), 115.66 (s),
We acknowledge the financial support from King Abdullah
University of Science and Technology to K.-W.H. and from National
Natural Science Foundation of China (21072030) and Fuzhou Uni-
versity (022318) to Z.W.
113.95 (s), 87.00 (q, J¼6.5 Hz), 75.25 (q, J¼52.3 Hz), 38.06 (s), 24.19
(s), 13.69 (s). GCeMS m/z 212 (Mþ), 143 (MþꢁCF3).
4.2.5. 1-Butyl-4-(3,3,3-trifluoroprop-1-ynyl)benzene (2f). 1H NMR
(500 MHz, CDCl3, 293 K):
d
ppm 7.47 (d, J¼8.1 Hz, 1H), 7.20 (t,
Supplementary data
J¼8.7 Hz, 1H), 2.73e2.53 (m, 1H), 1.60 (ddt, J¼11.9, 10.7, 5.2 Hz, 1H),
1.35 (tt, J¼15.5, 7.8 Hz, 2H), 0.97e0.91 (m, 2H). 19F NMR (470 MHz,
Copies of NMR spectra for all products. Supplementary data
related to this article can be found online at doi:10.1016/
j.tet.2011.12.085.
CDCl3):
d
ppm ꢁ51.77 (s, 3F). 13C NMR (126 MHz, CDCl3):
d ppm
146.43 (s), 132.40 (q, J¼1.4 Hz), 128.77 (s), 115.62 (q, J¼1.8 Hz),
113.96 (s), 87.00 (q, J¼6.5 Hz), 75.24 (q, J¼52.4 Hz), 35.73 (s), 33.22
(s), 22.28 (s), 13.87 (s). IR (KBr):
n 2961, 2932, 2862, 2252, 1608,
References and notes
1509, 1467, 1384, 1317, 1275, 1163, 1138, 871, 831, 688 cmꢁ1. GCeMS
m/z 226 (Mþ). HRMS (APPI): calculated for C17H10F3 (MþH):
227.10477; found: 227.10388.
€
1. (a) Muller, K.; Faeh, C.; Diederich, F. Science 2007, 317, 1881; (b) Purser, S.;
Moore, P. R.; Swallow, S.; Gouverneur, V. Chem. Soc. Rev. 2008, 37, 320; (c)
Hagmann, W. K. J. Med. Chem. 2008, 51, 4359.
2. (a) Kirsch, P. Modern Fluoroorganic Chemistry: Synthesis, Reactivity, Applications;
Wiley-VCH: Weinheim, 2004; (b) Isanbor, C.; O’Hagan, D. J. Fluorine Chem.
2006, 127, 303.
3. For selected reviews for trifloromethylation, see: (a) Schlosser, M. Angew Chem.,
Int. Ed. 2006, 45, 5432; (b) Ma, J.-A.; Cahard, D. J. Fluorine Chem. 2007, 128, 975;
(c) Prakash, G. K. S.; Chacko, S. Curr. Opin. Drug Discovery Dev. 2008, 11, 793; (d)
Kieltsch, I.; Eisenberger, P.; Stanek, K.; Togni, A. Chimia 2008, 62, 260; (e)
Tomashenko, O. A.; Grushin, V. V. Chem. Rev. 2011, 111, 4475; (f) Roy, S.; Gregg,
B. T.; Gribble, G. W.; Le, V.-D.; Roy, S. Tetrahedron 2011, 67, 2161.
4.2.6. 9-(3,3,3-Trifluoroprop-1-ynyl)phenanthrene (2g). 1H NMR
(400 MHz, CDCl3, 293 K):
d
ppm 8.63 (m, 2H), 8.25 (t, J¼5.2 Hz, 1H),
8.06 (s, 1H), 7.81 (d, 1H), 7.70 (m, 3H), 7.62 (t, J¼7.6 Hz 1H). 19F NMR
(377 MHz, CDCl3):
d
ppm ꢁ50.1 (s, 3F). 13C NMR (100.7 MHz,
CDCl3):
d
ppm 134.98 (d, J¼1.9 Hz), 131.19 (s), 130.30 (s), 130.07 (s),
129.92 (s), 129.06 (s), 128.87 (s), 127.63 (d, J¼3.34 Hz), 127.30 (s),
126.10 (s), 122.97 (s), 122.72 (s), 114.84 (q, J¼158.4 Hz), 85.43 (q,
4. For stoichiometric trifluoromethylation, see: (a) Grushin, V. V.; Marshall, W. J. J.
Am. Chem. Soc. 2006, 128, 4632; (b) Grushin, V. V.; Marshall, W. J. J. Am. Chem.
Soc. 2006, 128, 12644; (c) Dubinina, G. G.; Furutachi, H.; Vicic, D. A. J. Am. Chem.
Soc. 2008, 130, 8600; (d) Dubinina, G. G.; Ogikubo, J.; Vicic, D. A. Organometallics
2008, 27, 6233; (e) Chu, L.; Qing, F.-L. Org. Lett. 2010, 12, 5060; (f) Ball, N. D.;
Kampf, J. W.; Sanford, M. S. J. Am. Chem. Soc. 2010, 132, 2878; (g) Senecal, T. D.;
Parsons, A. T.; Buchwald, S. L. J. Org. Chem. 2011, 76, 1174; (h) Morimoto, H.;
Tsubogo, T.; Litvinas, N. D.; Hartwig, J. F. Angew. Chem., Int. Ed. 2011, 50, 3793; (i)
J¼6.2 Hz), 79.71 (q, J¼52.1 Hz). IR (KBr):
n 2239, 1330, 1286, 1272,
1106, 1059, 892, 724 cmꢁ1. GCeMS m/z 270 (Mþ). HRMS: calculated
for C17H9F3: 270.06509; found: 270.06461.
4.2.7. 1-Methoxy-4-(3,3,3-trifluoroprop-1-ynyl)benzene (2h).20 1H
NMR (400 MHz, CDCl3, 293 K):
d
ppm 7.54 (d, J¼8.8 Hz, 2H), 6.94 (d,
ꢀ
Tomashenko, O. A.; Escudero-Adan, E. C.; Martínez Belmonte, M.; Grushin, V. V.
J¼8.9 Hz, 2H). 19F NMR (377 MHz, CDCl3):
d
ppm ꢁ49.4 (s, 3F). 13
C
Angew. Chem., Int. Ed. 2011, 50, 7655; (j) Urban, C.; Cadoret, F.; Blazejewski, J.-C.;
Magnier, E. Eur. J. Org. Chem. 2011, 4862.
5. Weng, Z.; Lee, R.; Jia, W.; Yuan, Y.; Wang, W.; Xue, F.; Huang, K.-W. Organo-
NMR (100.7 MHz, CDCl3):
d ppm 161.68 (s), 134.30 (s), 114.49 (s),
87.20 (d, J¼6.5 Hz), 74.91(d, J¼52.4 Hz), 55.51 (s). GCeMS m/z 200
metallics 2011, 30, 3229.
(Mþ).
6. (a) Oishi, M.; Kondo, H.; Amii, H. Chem. Commun. 2009, 1909; (b) Inoue, M.;
Araki, K.; Kawada, K. Japanese Patent JP 2009-234921, 2009; (c) Cho, E. J.;
Senecal, T. D.; Kinzel, T.; Zhang, Y.; Watson, D. A.; Buchwald, S. L. Science 2010,
328, 1679; (d) Mu, X.; Chen, S.; Zhen, X.; Liu, G. Chem.dEur. J. 2011, 17, 6039.
7. Liu, T.; Shen, Q. Org. Lett. 2011, 13, 2342.
8. (a) Wang, X.; Truesdale, L.; Yu, J.-Q. J. Am. Chem. Soc. 2010, 132, 3648; (b) Xu, J.;
Luo, D.-F.; Xiao, B.; Liu, Z.-J.; Gong, T.-J.; Fu, Y.; Liu, L. Chem. Commun. 2011, 4300.
9. Knauber, T.; Arikan, F.; Roeschenthaler, G.-V.; Goossen, L. J. Chem.dEur. J. 2011,
17, 2689.
4.2.8. 1-Phenoxy-4-(3,3,3-trifluoroprop-1-ynyl)benzene
NMR (400 MHz, CDCl3, 293 K):
ppm 7.58 (d, J¼8.6 Hz, 2H), 7.48 (t,
(2i).17 1H
d
J¼7.6 Hz, 2H), 7.29 (t, J¼7.3 Hz, 1H), 7.15 (d, J¼7.8 Hz, 2H), 7.04 (d,
J¼8.3 Hz, 2H). 19F NMR (377 MHz, CDCl3):
d
ppm ꢁ49.5 (s, 3F). 13
C
NMR (100.7 MHz, CDCl3):
d ppm 160.24 (s), 155.62 (s), 134.43 (s),
10. Lundgren, R. J.; Stradiotto, M. Angew. Chem., Int. Ed. 2010, 49, 9322.
11. Grushin, V. V. Acc. Chem. Res. 2010, 43, 160.
130.24 (s), 124.79 (s), 120.23 (s), 118.06 (s), 113.87 (s), 86.65 (d,
J¼6.9 Hz), 75.38 (q, J¼52.9 Hz).
12. (a) Brisdon, A. K.; Crossley, I. R. Chem. Commun. 2002, 2420; (b) Konno, T.;
Daitoh, T.; Noiri, A.; Chae, J.; Ishihara, T.; Yamanaka, H. Org. Lett. 2004, 6, 933; (c)
Zhang, X.-G.; Chen, M.-W.; Zhong, P.; Hu, M.-L. J. Fluorine Chem. 2008, 129, 335;
(d) Grushin, K. S.; Nenov, M. N.; Dynnik, V. V.; Semushina, S. G.; Pakhomova, I. A.;
Murashev, A. N.; Kokoz, Y. M. Biol. Membr. 2008, 25, 377; (e) Shimizu, M.; Hi-
gashi, M.; Takeda, Y.; Murai, M.; Jiang, G.; Asai, Y.; Nakao, Y.; Shirakawa, E.;
Hiyama, T. Future Med. Chem. 2009, 1, 921; (f) Konno, T.; Kinugawa, R.; Morigaki,
4.2.9. 1-Bromo-2-(3,3,3-trifluoroprop-1-ynyl)benzene (2j). 1H NMR
(400 MHz, CDCl3, 293 K):
2H), 19F NMR (377 MHz, CDCl3):
(100.7 MHz, CDCl3):
d ppm 7.63 (m, 1H), 7.56 (m, 1H). 7.34 (m,
d
ppm ꢁ50.2 (s, 3F). 13C NMR
d
ppm 134.51(s), 133.00 (s), 132.16 (s), 127.41

Z. Weng et al. / Tetrahedron 68 (2012) 2527e2531
2531
A.; Ishihara, T. J. Org. Chem. 2009, 74, 8456; (g) Gunay, A.; Muller, C.; Lachicotte,
R. J.; Brennessel, W. W.; Jones, W. D. Organometallics 2009, 28, 6524.
13. Yoneda, N.; Matsuoka, S.; Miyaura, N.; Fukuhara, T.; Suzuki, A. Bull. Chem. Soc.
Jpn. 1990, 63, 2124.
14. (a) Laurent, A.; Le, D. I.; Selmi, A. Tetrahedron Lett. 1991, 32, 3071; (b) Konno, T.;
Chae, J.; Kanda, M.; Nagai, G.; Tamura, K.; Ishihara, T.; Yamanaka, H. Tetrahedron
2003, 59, 7571.
16. Klyuchinskii, S. A.; Zavgorodnii, V. S.; Lebedev, V. B.; Petrov, A. A. Zh. Obshch.
Khim. 1986, 56, 1663.
17. Chu, L.; Qing, F.-L. J. Am. Chem. Soc. 2010, 132, 7262.
18. Kawatsura, M.; Yamamoto, M.; Namioka, J.; Kajita, K.; Hirakawa, T.; Itoh, T. Org.
Lett. 2011, 13, 1001.
19. Hiyama, T.; Sato, K.-i. Synlett 1990, 53.
20. Kobayashi, Y.; Yamashita, T.; Takahashi, K.; Kuroda, H.; Kumadaki, I. Tetrahedron
Lett. 1982, 23, 343.
15. Umemoto, T.; Ishihara, S. J. Am. Chem. Soc. 1993, 115, 2156.