Palladium-catalyzed decarboxylative trifluoroethylation of aryl alkynyl carboxylic acids

Article abstract of DOI:10.1021/jo5003032

A trifluoroethylation of alkynes through a palladium-catalyzed decarboxylative coupling reaction was developed. When alkynyl carboxylic acids and ICH₂CF₃ were allowed to react with [Pd(? ³-allyl)Cl]₂/XantPhos and Cs₂CO₃ in N,N-dimethylformamide (DMF) at 80 °C for 1 h, the desired products were formed in good yields. This catalytic system showed high functional group tolerance.

Full text of DOI:10.1021/jo5003032

Note
pubs.acs.org/joc
Palladium-Catalyzed Decarboxylative Trifluoroethylation of Aryl
Alkynyl Carboxylic Acids
Jinil Hwang,† Kyungho Park,† Juseok Choe,† Hongkeun Min,† Kwang Ho Song,*,‡ and Sunwoo Lee*,†
†Department of Chemistry, Chonnam National University, Gwangju 500-757, Republic of Korea
‡Department of Chemical & Biological Engineering, Korea University, Seoul 136-713, Republic of Korea
S
* Supporting Information
ABSTRACT: A trifluoroethylation of alkynes through a
palladium-catalyzed decarboxylative coupling reaction was
developed. When alkynyl carboxylic acids and ICH2CF3 were
allowed to react with [Pd(η3-allyl)Cl]2/XantPhos and Cs2CO3
in N,N-dimethylformamide (DMF) at 80 °C for 1 h, the de-
sired products were formed in good yields. This catalytic system showed high functional group tolerance.
he introduction of fluorine and/or trifluoromethyl groups
decarboxylative couplings have been reported.22 However,
Tto organic compounds is a very important process to decarboxylative coupling reactions with sp3 carbons are rare.
Herein we report the decarboxylative coupling reaction of aryl
alkynyl carboxylic acids with ICH2CF3 using palladium as the
catalyst.
improve the physicochemical and bioactive properties of the
compounds.1 According to recent reports, 20−30% of pharma-
ceutical and agrochemicals have fluorine and/or trifluoromethyl
groups.2 A number of synthetic methods for fluorination and
trifluoromethylation have been consistently reported; however,
the number of reports on these methodologies has increased
greatly in the past five years.3
To achieve our goal, a number of parameters were screened in
the reaction of phenyl propiolic acid and ICH2CF3. The results
are summarized in Table 1. Employment of the catalytic systems
Pd(PPh3)Cl2/dppb/DMSO/(Cs2CO3 or DBU), which have
been widely used in the decarboxylative coupling of aryl halides
and aryl alkynyl carboxylic acids, did not produce satisfactory
results (entries 1 and 2). When we used DABCO, which was
chosen by Xu as the best base in the coupling of terminal alkynes
and ICH2CF3, the desired product was formed in 30% yield
(entry 3). The palladium source was changed to Pd2(dba)3,
and a variety of ligands were screened. Sterically bulky
monophosphines, such as tBuDavePhos, DavePhos, and XPhos
showed yields of 5%, 9%, and 10%, respectively (entries 4−6).
However, dppb and dppf, which are good ligands in the
decarboxylative coupling of alkynyl carboxylic acids and aryl
halides, did not give any desired product (entries 7 and 8).
Chelating diphosphine ligands, such as DIOP, DPEPhos, and
XantPhos, provided product in yields of 5%, 16%, and 27%,
respectively (entries 9−11). With XantPhos as the ligand, the
palladium source was screened. Pd(PPh3)Cl2 afforded the
desired product in 81% yield (entry 12). Other palladium
sources showed moderate yields (entries 13−15). To find the
matched cases of palladium source and solvent, other solvents
were tested. In the case of Pd(PPh3)2Cl2, all of the tested
solvents, including as DMF, DMSO, and dioxane, gave
unsatisfactory results (entries 16−18). When [Pd(η3-allyl)Cl]2
was employed as the palladium source, DMF showed better
results than toluene did. This condition showed the best
result (entry 19). DMSO provided a 28% yield of the product
(entry 20). In the reaction with 1,4-dioxane, the desired product
The methods that have been studied even more are transition-
metal-catalyzed (or -mediated) fluorination4 and trifluoro-
methylation5 with commercially available fluorinating reagents
or the development of efficient new fluorinating reagents. Metal
fluorides and amine fluoride salts have been employed with
nucleophilic and electrophilic fluorine sources, respectively.6
As trifluoromethyl sources, TMSCF3,7 TESCF3,8 ICF3,9
CF3CO2H,10 Togni’s reagent,11 Umemoto’s reagent,12 and
Hartwig reagents13 have been used. Palladium, copper, gold,
iron, and silver have been used as transition-metal sources.14
In addition, the use of trifluoroethylation to form bonds
between sp2 or sp3 carbons and CH2CF3 have also been stud-
ied.15 Recently, the Xu group reported that the Sonogashira-type
coupling reaction of terminal alkynes and ICH2CF3 afforded
the corresponding trifluoroethylated alkynes in good yields.16
Although the Xu group suggested that this method has several
advantages compared with the previous methods reported by
Shibata,17 Ma,18 and Szabo19 independently, it has some draw-
backs in that terminal alkynes also have to be prepared through
multistep reactions, including Sonogashira coupling and a
deprotection process.
Instead of terminal alkynes, the use of alkynyl carboxylic acids
as an alkyne source has several advantages. They are easily pre-
pared from the coupling reaction of aryl halides and propiolic
acid and are simply purified by using an acid and base workup
process. In addition, they are stable for storage and easy han-
dling.20 Since 2008, a variety of decarboxylative coupling reac-
tions of alkynyl carboxylic acids have been developed by
our group and others.21 In addition, a number of catalytic
Received: February 11, 2014
Published: March 16, 2014
© 2014 American Chemical Society
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Note
a
Table 1. Optimization of the Conditions for the Trifluoroethylation of Alkynes
b
Entry
Catalyst
Ligand
Base
Solvent
DMSO
Yield (%)
c
1
2
Pd(PPh3)2Cl2
Pd(PPh3)2Cl2
Pd(PPh3)2Cl2
Pd2(dba)3
dppb
Cs2CO3
DBU
10
trace
30
5
dppb
DMSO
DMSO
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
DMF
3
dppb
DABCO
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
d
4
tBuDavePhos
e
5
Pd2(dba)3
DavePhos
9
f
6
Pd2(dba)3
XPhos
10
trace
trace
5
7
Pd2(dba)3
dppb
g
8
Pd2(dba)3
dppf
h
9
Pd2(dba)3
DIOP
i
10
11
12
13
14
15
16
17
18
19
20
21
Pd2(dba)3
DPEPhos
16
27
81
56
35
44
24
44
42
87
28
66
j
Pd2(dba)3
XantPhos
Pd(PPh3)2Cl2
[Pd(η3-allyl)Cl]2
Pd(OAc)2
XantPhos
XantPhos
XantPhos
XantPhos
XantPhos
XantPhos
XantPhos
XantPhos
XantPhos
Xantphos
Pd(CH3CN)2Cl2
Pd(PPh3)2Cl2
Pd(PPh3)2Cl2
Pd(PPh3)2Cl2
[Pd(η3-allyl)Cl]2
[Pd(η3-allyl)Cl]2
[Pd(η3-allyl)Cl]2
DMSO
1,4-dioxane
DMF
DMSO
1,4-dioxane
a
Reaction conditions: 1a (0.6 mmol), ICH2CF3 (0.3 mmol), Pd (0.03 mmol), ligand (0.03 mmol), and base (0.3 mmol) were reacted in the solvent
b
c
(1.0 mL) at 80 °C for 1 h. Yields were determined by 19F NMR spectroscopy and gas chromatography with an internal standard. 1,4-
d
e
Bis(diphenylphosphino)butane. 2′-(Di-tert-butylphosphino)-N,N-dimethylbiphenyl-2-amine. 2-Dicyclohexylphosphino-2′-(N,N-dimethylamino)-
f
g
h
biphenyl. 2-Dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl. 1,1′-Bis(diphenylphosphino)ferrocene. 2,3-O-isopropylidene-2,3-dihydroxy-1,4-
i
j
bis(diphenylphosphino)butane. Bis[(2-diphenylphosphino)phenyl] ether. 4,5-Bis(diphenylphosphino)-9,9-dimethylxanthene.
was formed in 66% yield (entry 21). In all cases, the esteri-
fication product, 2,2,2-trifluoroethyl 3-phenylpropioate, was
not found in the reaction mixture under these optimized
conditions.
iodides with propiolic acid and decarboxylative coupling with
ICH2CF3. Among the tested conditions in Table 1, the
conditions showing the best yield were first employed in the
reaction of phenyl iodide and propiolic acid, and then ICH2CF3
was added to the reaction mixture. The results are summarized in
Table 3. With XantPhos and Cs2CO3, palladium sources, such as
Pd(PPh3)2Cl2 and [Pd(η3-allyl)Cl]2, and solvents were tested.
When Pd(PPh3)2Cl2 was employed in toluene or DMSO, the
desired product was not formed (entries 1 and 2). In 1,4-dioxane
solvent, the yield of product was 17% (entry 3). Changing the
palladium source to [Pd(η3-allyl)Cl]2 afforded the desired
product in yields of 45% and 12% in DMF and 1,4-dioxane,
respectively (entries 4 and 5). Under these conditions, when
4-iodotoluene and 2-iodoanisole were employed, the desired
coupling products were formed in yields of 43% and 39%,
respectively (entries 6 and 7).
To understand the reactivity of ICH2CF3 in this decarbox-
ylative coupling, competitive reactions were carried out, as
shown in Table 4. The decarboxylative coupling reaction with
ICH2CF3 showed lower reactivity than those with phenyl iodide
and bromide. However, it showed a higher reactivity than phenyl
chloride did. On the basis of these results, the order of the
reactivity toward decarboxylative coupling is as follows: PhI >
PhBr > ICH2CF3 ≫ PhCl.
To test the substrate scope, the optimized conditions
were employed in the decarboxylative coupling reaction of a
variety of aryl alkynyl carboxylic acids. The results are sum-
marized in Table 2. All of the starting materials were prepared by
the coupling reactions of propiolic acid with aryl iodides or
bromides. Phenylpropiolic acid afforded (4,4,4-trifluorobut-1-
ynyl)benzene in 87% yield based on 19F NMR analysis (entry 1).
However, we failed to obtain it with purity because of its high
volatility. Alkyl-substituted aryl alkynyl carboxylic acids 1b−e
provided the corresponding trifluoroethylated products in
yields of 85%, 65%, 77%, and 83%, respectively (entries 2−5).
Methoxy-substituted substrates 1f and 1g showed yields of 89%
and 61%, respectively (entries 6 and 7). Substrates bearing
electron-withdrawing functional groups, such as ketone, ester,
and nitrile, exhibited moderate yields in the coupling reaction
(entries 8−10). 1-Naphthyl and 4′-biphenyl alkynyl carboxylic
acids afforded the corresponding coupled products in yields
of 88% and 64%, respectively (entries 11 and 12). Fluoro-
substituted substrate 1m provided the desired product in
moderate yield (entry 13). Thiophene-substituted alkynyl
carboxylic acid 1n also produced the trifluoroethylated product
in 45% yield (entry 14).
In summary, we have developed a synthesis of trifluoroethy-
lated alkynes from the palladium-catalyzed decarboxylative
coupling of aryl alkynyl carboxylic acids with ICH2CF3. The
use of aryl alkynyl carboxylic acids has several advantages,
including simple preparation. The optimized conditions were
To expand this methodology to the one-pot synthesis of
trifluorobutynyl arenes from propiolic acid, we investigated the
optimized conditions for sequential Sonogashira coupling of aryl
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Note
a
Table 2. Trifluoroethylation of Aryl Alkynyl Carboxylic Acids
a
Reaction conditions: 1 (6.0 mmol), ICH2CF3 (3.0 mmol), [Pd(η3-allyl)Cl]2 (0.15 mmol), XantPhos (0.3 mmol), and Cs2CO3 (3.0 mmol) were
b
c
reacted in DMF (10.0 mL) at 80 °C for 1 h. Isolated yields are averages of at least two runs. Yields were determined by 19F NMR spectroscopy
with an internal standard.
a
Table 3. One-Pot Synthesis of Trifluorobut-1-ynyl Arenes from Propiolic Acid
Entry
Ar
C6H5
Catalyst
Solvent
toluene
Product
Yield (%)
1
2
3
4
5
6
7
Pd(PPh3)2Cl2
−
−
2a
2a
2a
2d
2f
−
−
17
45
12
43
39
C6H5
Pd(PPh3)2Cl2
DMSO
1,4-dioxane
DMF
C6H5
Pd(PPh3)2Cl2
C6H5
[Pd(η3-allyl)Cl]2
[Pd(η3-allyl)Cl]2
[Pd(η3-allyl)Cl]2
[Pd(η3-allyl)Cl]2
C6H5
1,4-dioxane
DMF
4-MeC6H4
2-MeOC6H4
DMF
a
Reaction conditions: ArI (6.0 mmol), propiolic acid (12.0 mmol), Pd (1.2 mmol), XantPhos (1.2 mmol), and Cs2CO3 (24.0 mmol) were reacted in
the solvent (20.0 mL) at 50 °C for 5 h, and then ICH2CF3 (3.0 mmol) was added and reacted at 80 °C for 1 h.
such that the substrates were reacted with [Pd(η3-allyl)Cl]2/
XantPhos and Cs2CO3 in DMF at 80 °C for 1 h. This catalytic
system provided shorter reaction times and showed a broad
substrate scope. In addition, it exhibited high tolerance toward
functional groups such as ketone, ester, nitrile, and fluoro groups.
Furthermore, the desired trifluoroethylated alkynyl compounds
could be obtained from propiolic acid using a one-pot sequential
Sonogashira coupling and decarboxylative coupling reaction.
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The Journal of Organic Chemistry
Note
19F NMR (282 MHz, CDCl3) δ −67.06 (t, J = 9.6 Hz); HRMS (ESI,
TOF) calcd for C12H12F3 [M + H]+ 213.0891, found 213.0891.
1-Methoxy-2-(4,4,4-trifluorobut-1-ynyl)benzene (2f). 3-(2-
Methoxyphenyl)propiolic acid (1f) (1.06 g) afforded the product 2f
Table 4. Competitive Reactions of ICH2CF3 and Phenyl
Halides
1
(571.9 mg, 2.66 mmol, 89%) as a yellow oil. H NMR (300 MHz,
CDCl3) δ 7.46 (dd, J = 7.6, 1.7 Hz, 1H), 7.38−7.29 (m, 1H), 6.92 (dd,
J = 16.9, 8.3 Hz, 2H), 3.88 (s, 3H), 3.36 (q, J = 9.6 Hz, 2H); 13C{1H}
NMR (75 MHz, CDCl3) δ 160.6, 134.1, 130.4, 124.6 (q, J = 275 Hz),
120.7, 111.6, 110.9, 81.7 (q, J = 5.1 Hz), 81.0, 55.9, 27.2 (q, J = 34.5 Hz);
19F NMR (282 MHz, CDCl3) δ −66.83 (t, J = 9.6 Hz); HRMS (ESI,
TOF) calcd for C11H10OF3 [M + H]+ 215.0684, found 215.0680.
1,2,3-Trimethoxy-5-(4,4,4-trifluorobut-1-ynyl)benzene (2g).
3-(3,4,5-Trimethoxyphenyl)propiolic acid (1g) (1.42 g) afforded
the product 2g (501.9 mg, 1.83 mmol, 61%) as a yellow oil. 1H NMR
(300 MHz, CDCl3) δ 6.68 (s, 2H), 3.85 (s, 12H), 3.27 (q, J = 9.6 Hz,
2H); 13C{1H} NMR (75 MHz, CDCl3) δ 133.0, 139.1, 124.1 (q, J =
275.1 Hz), 117.1, 109.0, 84.3, 60.9, 56.1, 26.7 (q, J = 34.5 Hz); 19F NMR
(282 MHz, CDCl3) δ −66.81 (t, J = 9.6 Hz); HRMS (ESI, TOF) calcd
for C13H14O3F3 [M + H]+ 275.0895, found 275.0897.
Yields (%)
Entry
X
2a
3a
83
1
2
3
I
trace
12
Br
Cl
72
56
trace
EXPERIMENTAL SECTION
■
1-(4-(4,4,4-Trifluorobut-1-ynyl)phenyl)ethanone (2h).16 3-(4-
Acetylphenyl)propiolic acid (1h) (1.13 g) afforded the product 2h
General Procedure for the Synthesis of 2,2,2-Trifluoroethy-
lated Alkynes. Aryl alkynyl carboxylic acid (6.0 mmol), ICH2CF3
(630 mg, 3.0 mmol), [Pd(η3-allyl)Cl]2 (54.9 mg, 0.15 mmol), XantPhos
(173.6 mg, 0.3 mmol), Cs2CO3 (977.5 mg, 3.0 mmol), and DMF
(10 mL) were added to a one-neck flask. The flask was sealed, and the
reaction mixture was allowed to stir at 80 °C for 1 h. The mixture was
then poured into water and extracted with Et2O (3 × 20 mL). The
combined ethyl acetate extracts were dried over MgSO4 and passed
through Celite. The solvent was removed under vacuum, and the
resulting crude product was purified by flash chromatography on silica
gel. The products 2a−f, 2i, and 2k−n were eluted with pentane, and 2g,
2h, and 2j were eluted with 1:4 ethyl acetate/hexane.
1
(441.1 mg, 1.95 mmol, 65%) as a yellow oil. H NMR (300 MHz,
CDCl3) δ 7.90 (d, J = 8.6 Hz, 2H), 7.52 (d, J = 8.5 Hz, 2H), 3.31 (q, J =
9.5 Hz, 2H), 2.59 (s, 3H); 13C{1H} NMR (75 MHz, CDCl3) δ 197.2,
136.6, 131.9, 128.1, 126.8, 124.0 (q, J = 275 Hz), 83.5, 80.8 (q, J =
5.2 Hz), 26.7 (q, J = 35 Hz), 26.5; 19F NMR (282 MHz, CDCl3)
δ −66.68 (t, J = 9.5 Hz); MS m/z (relative intensity) 226 (34), 211
(100), 182 (12), 163 (18), 133 (52), 107 (11), 88 (8).
Methyl 4-(4,4,4-Trifluorobut-1-ynyl)benzoate (2i).16 3-(4-
(Methoxycarbonyl)phenyl)propiolic acid (1i) (1.23 g) afforded the
1
product 2i (450.5 mg, 1.86 mmol, 62%) as a yellow oil. H NMR
(4,4,4-Trifluorobut-1-ynyl)benzene (2a).18 Phenylpropiolic acid
(1a) (876.8 mg) afforded the product 2a (480.7 mg, 2.61 mmol, 87%) as
a colorless oil. 19F NMR (282 MHz, CDCl3) δ −66.83 (t, J = 9.6 Hz);
MS m/z (relative intensity) 184 (58), 164 (12), 133 (10), 115 (100),
89 (18).
(300 MHz, CDCl3) δ 7.98 (d, J = 8.7 Hz, 2H), 7.49 (d, J = 8.6 Hz, 2H),
3.91 (s, 3H), 3.30 (q, J = 9.5 Hz, 2H); 13C{1H} NMR (75 MHz, CDCl3)
δ 166.3, 131.7, 130.0, 129.4, 126.7, 124.0 (q, J = 275 Hz), 83.5, 80.5 (q,
J = 5 Hz), 52.1, 26.7 (q, J = 34.7 Hz); 19F NMR (282 MHz, CDCl3)
δ −66.75 (t, J = 9.5 Hz); MS m/z (relative intensity) 242 (50), 211
(100), 182 (12), 163 (11), 133 (48).
1-Methyl-2-(4,4,4-trifluorobut-1-ynyl)benzene (2b).23 3-o-
Tolylpropiolic acid (1b) (961.0 mg) afforded the product 2b
4-(4,4,4-Trifluorobut-1-ynyl)benzonitrile (2j).16 3-(4-
Cyanophenyl)propiolic acid (1j) (1.03 g) afforded the product 2j
1
(505.4 mg, 2.55 mmol, 85%) as a yellow oil. H NMR (300 MHz,
1
(395.3 mg, 1.89 mmol, 63%) as a yellow oil. H NMR (300 MHz,
CDCl3) δ 7.40 (d, J = 7.5 Hz, 1H), 7.25−7.09 (m, 3H), 3.31 (q, J =
9.5 Hz, 2H), 2.42 (s, 3H); 13C{1H} NMR (75 MHz, CDCl3) δ 140.6,
132.0, 129.4, 128.6, 125.5, 124.3 (q, J = 275 Hz), 121.9, 83.3, 81.3 (q, J =
5 Hz), 26.9 (q, J = 34.5 Hz), 20.5; 19F NMR (282 MHz, CDCl3)
δ −66.98 (t, J = 9.5 Hz); MS m/z (relative intensity) 198 (69), 129
(100), 115 (23), 77 (15), 51 (19).
CDCl3) δ 7.66−7.57 (m, 2H), 7.57−7.49 (m, 2H), 3.31 (q, J = 9.4 Hz,
2H); 13C{1H} NMR (75 MHz, CDCl3) δ 132.4, 132.0, 127.0, 123.9 (q,
J = 275 Hz), 118.2, 112.2, 82.8, 82.1 (q, J = 5 Hz), 26.9 (q, J = 34.8 Hz);
19F NMR (282 MHz, CDCl3) δ −66.54 (t, J = 9.4 Hz); MS m/z (relative
intensity) 209 (52), 189 (18), 140 (100), 113 (28), 63 (18).
1-(4,4,4-Trifluorobut-1-ynyl)naphthalene (2k).18 3-(Naphthalen-
1-yl)propiolic acid (1k) (1.18 g) afforded the product 2k (618.3 mg,
2.64 mmol, 88%) as a yellow oil. 1H NMR (300 MHz, CDCl3) δ 8.28 (d,
J = 8.3 Hz, 1H), 7.77 (dd, J = 7.8, 4.3 Hz, 2H), 7.64 (d, J = 7.1 Hz, 1H),
7.54 (ddd, J = 8.3, 6.9, 1.4 Hz, 1H), 7.46 (ddd, J = 8.1, 6.9, 1.4 Hz, 1H),
7.34 (dd, J = 8.3, 7.2 Hz, 1H), 3.36 (q, J = 9.5 Hz, 2H); 13C{1H} NMR
(75 MHz, CDCl3) δ 133.4, 133.1, 130.8, 129.2, 128.3, 126.9, 126.4,
125.8, 125.0, 124.3 (q, J = 275 Hz), 119.7, 82.6, 82.3 (q, J = 5 Hz), 27.0
(q, J = 34.5 Hz); 19F NMR (282 MHz, CDCl3) δ −66.60 (t, J = 9.6 Hz);
MS m/z (relative intensity) 234 (100), 165 (88), 139 (8), 82 (9), 63 (7).
4-(4,4,4-Trifluorobut-1-ynyl)biphenyl (2l).16 3-(Biphenyl-4-yl)-
propiolic acid (1l) (1.33 g) afforded the product 2l (499.7 mg,
1.92 mmol, 64%) as a white solid. 1H NMR (300 MHz, CDCl3) δ 7.61−
7.49 (m, 6H), 7.48−7.40 (m, 2H), 7.39−7.32 (m, 1H), 3.29 (q, J =
9.6 Hz, 2H); 13C{1H} NMR (75 MHz, CDCl3) δ 141.5, 140.2, 132.2,
128.9, 127.7, 127.02, 126.98, 124.2 (q, J = 275.1 Hz), 121.0, 84.2, 78.1
(q, J = 5.1 Hz), 26.9 (q, J = 34.6 Hz); 19F NMR (282 MHz, CDCl3) δ
−66.80 (t, J = 9.6 Hz); MS m/z (relative intensity) 260 (100), 191 (67),
165 (10), 94 (12), 82 (8).
1-Methyl-3-(4,4,4-trifluorobut-1-ynyl)benzene (2c).23 3-m-
Tolylpropiolic acid (1c) (961.0 mg) afforded the product 2c
1
(386.5 mg, 1.95 mmol, 65%) as a yellow oil. H NMR (300 MHz,
CDCl3) δ 7.31−7.24 (m, 2H), 7.18−7.11 (m, 2H), 3.20 (q, J = 9.6 Hz,
2H), 2.28 (s, 3H); 13C{1H} NMR (75 MHz, CDCl3) δ 138.0, 132.4,
129.6, 128.9, 128.2, 124.3 (q, J = 275 Hz), 122.1, 84.5, 77.1 (q, J = 5 Hz),
26.6 (q, J = 34.5 Hz), 21.0; 19F NMR (282 MHz, CDCl3) δ −66.92 (t, J =
9.6 Hz); MS m/z (relative intensity) 198 (83), 183 (12), 129 (100), 102
(8), 77 (9), 63 (11).
1-Methyl-4-(4,4,4-trifluorobut-1-ynyl)benzene (2d).18 3-p-
Tolylpropiolic acid (1d) (961.0 mg) afforded the product 2d
1
(457.8 mg, 2.31 mmol, 77%) as a yellow oil. H NMR (300 MHz,
CDCl3) δ 7.32 (d, J = 8.1 Hz, 2H), 7.09 (d, J = 7.2 Hz, 2H), 3.22 (q, J =
9.6 Hz, 2H), 2.32 (s, 3H); 13C{1H} NMR (75 MHz, CDCl3) δ 138.8,
131.7, 129.0, 124.3 (q, J = 275 Hz), 119.1, 84.4, 76.7 (q, J = 5 Hz), 26.7
(q, J = 34.5 Hz), 21.3; 19F NMR (282 MHz, CDCl3) δ −66.95 (t, J =
9.6 Hz); MS m/z (relative intensity) 198 (69), 183 (10), 129 (100), 102
(6), 77 (10).
2,4-Dimethyl-1-(4,4,4-trifluorobut-1-ynyl)benzene (2e). 3-
(2,4-Dimethylphenyl)propiolic acid (1e) (1.05 g) afforded the product
1-Fluoro-4-(4,4,4-trifluorobut-1-ynyl)benzene (2m).18 3-(4-
Fluorophenyl)propiolic acid (1m) (984.8 mg) afforded the product
2m (339.6 mg, 1.68 mmol, 56%) as a yellow oil. 1H NMR (300 MHz,
CDCl3) δ 7.52−7.33 (m, 2H), 7.08−6.92 (m, 2H), 3.24 (q, J = 9.6 Hz,
2H); 13C{1H} NMR (75 MHz, CDCl3) δ 162.8 (d, J = 248 Hz), 133.8
(d, J = 8.4 Hz), 124.2 (q, J = 275 Hz), 118.3 (d, J = 3.5 Hz), 115.6
1
2e (528.4 mg, 2.49 mmol, 83%) as a yellow oil. H NMR (300 MHz,
CDCl3) δ 7.28 (d, J = 7.8 Hz, 1H), 7.00 (s, 1H), 6.92 (d, 7.8 Hz, 1H),
3.27 (q, J = 9.6 Hz, 2H), 2.37 (s, 3H), 2.29 (s, 3H); 13C{1H} NMR
(75 MHz, CDCl3) δ 140.4, 138.7, 131.9, 130.3, 127.6 (q, J = 275 Hz),
126.3, 118.9, 83.4, 80.5 (q, J = 5 Hz), 26.9 (q, J = 34.5 Hz), 21.3, 20.3;
3270
dx.doi.org/10.1021/jo5003032 | J. Org. Chem. 2014, 79, 3267−3271

The Journal of Organic Chemistry
Note
(d, J = 22 Hz), 83.3, 77.3 (q, J = 5 Hz), 26.7 (q, J = 34.6 Hz); 19F NMR
(282 MHz, CDCl3) δ −66.88 (t, J = 9.6 Hz); MS m/z (relative intensity)
202 (43), 182 (6), 151 (4), 133 (100), 83 (11).
(13) (a) Litvinas, N. D.; Fier, P. S.; Hartwig, J. F. Angew. Chem., Int. Ed.
2012, 51, 536−539. (b) Jiang, X.; Chu, L.; Qing, F.-L. J. Org. Chem.
2012, 77, 1251−1257.
2-(4,4,4-Trifluorobut-1-ynyl)thiophene (2n). 3-(Thiophen-2-
(14) For selected recent examples, see: Pd: (a) Mazzotti, A. R.;
Campbell, M. G.; Tang, P.; Murphy, J. M.; Ritter, T. J. Am. Chem. Soc.
2013, 135, 14012−14015. (b) Gao, Z.; Gouverneur, F.; Davis, B. G. J.
Am. Chem. Soc. 2013, 135, 13612−13615. (c) Truong, T.; Klimovica, K.;
Daugulis, O. J. Am. Chem. Soc. 2013, 135, 9342−9345. (d) Chen, Z.-M.;
Bai, W.; Wang, S.-H.; Yang, B.-M.; Yu, Y.-Q.; Zhang, F.-M. Angew.
Chem., Int. Ed. 2013, 52, 9781−9785. Au: (e) Arcadi, A.; Pietropaolo, E.;
Alvino, A.; Michelet, V. Org. Lett. 2013, 15, 2766−2769. Fe: (f) Bloom,
S.; Pitts, C. R.; Woltornist, R.; Giswold, A.; Holl, M. G.; Lectka, T. Org.
Lett. 2013, 15, 1722−1724. Ag: (g) Li, Z.; Song, L.; Li, C. J. Am. Chem.
Soc. 2013, 135, 4640−4643. (h) Wu, X.; Chu, L.; Qing, F.-L. Angew.
Chem., Int. Ed. 2013, 52, 2198−2202.
yl)propiolic acid (1n) (913.0 mg) afforded the product 2n (256.8 mg,
1
1.35 mmol, 45%) as a colorless oil. H NMR (300 MHz, CDCl3) δ
7.29−7.22 (m, 2H), 6.97 (dd, J = 5.1, 3.7 Hz, 1H), 3.29 (q, J = 9.6 Hz,
2H); 13C{1H} NMR (75 MHz, CDCl3) δ 130.0, 132.5, 127.2 (t, J =
41 Hz), 124.0 (q, J = 275 Hz), 122.0, 81.4 (q, J = 4.5 Hz), 77.7, 27.0 (q,
J = 34.7 Hz); 19F NMR (282 MHz, CDCl3) δ −66.66 (t, J = 9.5 Hz);
HRMS (ESI, TOF) calcd for C8H6F3S [M + H]+ 191.0142, found
191.0146.
ASSOCIATED CONTENT
■
S
* Supporting Information
(15) (a) McLoughlin, V. C. R.; Thrower, J. Tetrahedron 1969, 25,
5921−5940. (b) Solladie-Cavallo, A.; Suffert, J. Tetrahedron Lett. 1984,
25, 1897−1900. (c) Culkin, D. A.; Hartwig, J. F. Organometallics 2004,
23, 3398−3416. (d) Zhao, Y.; Hu, J. Angew. Chem., Int. Ed. 2012, 51,
1033−1036. (e) Long, Z.-Y.; Chen, Q.-Y. Tetrahedron Lett. 1998, 39,
8487−8490. (f) Matsuya, Y.; Ihara, D.; Fukuchi, M.; Honma, D.; Itoh,
K.; Tabuchi, A.; Nemoto, H.; Tsuda, M. Bioorg. Med. Chem. 2012, 20,
2564−2571.
1
Copies of H and 13C{1H} NMR spectra for all products.
This material is available free of charge via the Internet at
http://pubs.acs.org.
AUTHOR INFORMATION
■
Corresponding Authors
*E-mail: khsong@korea.ac.kr (K.H.S.).
*E-mail: sunwoo@chonnam.ac.kr (S.L.).
Notes
(16) Feng, Y.-S.; Xie, C.-Q.; Qiao, W.-L.; Xu, H.-J. Org. Lett. 2013, 15,
936−939.
(17) Kawai, H.; Furukawa, T.; Nomura, Y.; Tokunaga, E.; Shibata, N.
Org. Lett. 2011, 13, 3596−3599.
The authors declare no competing financial interest.
(18) Liu, C.-B.; Meng, W.; Li, F.; Wang, S.; Nie, J.; Ma, J.-A. Angew.
Chem., Int. Ed. 2012, 51, 6227−6230.
ACKNOWLEDGMENTS
́
(19) Zhao, T. S. N.; Szabo, K. J. Org. Lett. 2012, 14, 3966−3969.
■
(20) (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.
This research was supported by the Nano-Material Technology
Development Program through the National Research Founda-
tion (NRF) of Korea, funded by the Ministry of Education,
Science and Technology (Grant 2012M3A7B4049655). Spectral
data were obtained from the Korea Basic Science Institute,
Gwangju Branch.
(21) (a) Moon, J.; Jeong, M.; Nam, H.; Ju, J.; Moon, J. H.; Jung, H. M.;
Lee, S. Org. Lett. 2008, 10, 945−948. For a review, see: (b) Park, K.; Lee,
S. RSC Adv. 2013, 3, 14165−14182. (c) Goossen, L. J.; Goosen, K. Top.
Organomet. Chem. 2013, 44, 121−142.
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(b) Dzik, W. I.; Lange, P. P.; Gooßen, L. J. Chem. Sci. 2012, 3, 2671−
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