Three-Component One-Pot Synthesis of Unsymmetrical Diarylalkynes by Thermocontrolled Sequential Sonogashira Reactions Using Potassium Ethynyltrifluoroborate

Article abstract of DOI:10.1002/ejoc.201700110

Unsymmetrical diarylalkynes were synthesized in moderate to good yields through a three-component one-pot procedure involving thermocontrolled sequential Sonogashira reactions with potassium ethynyltrifluoroborate and two different reactive aryl halides. The one-pot procedure was initiated by the palladium/copper-catalyzed Sonogashira coupling of potassium ethynyltrifluoroborate to an aryl iodide or electron-deficient aryl bromide at 40 °C. Following a subsequent deboronative Sonogashira reaction of the in situ generated potassium (arylethynyl)trifluoroborate, a second coupling to a less-active electron-rich aryl bromide at 80 °C, without any additional palladium/copper catalyst or base, gave rise to unsymmetrical diarylalkynes.

Full text of DOI:10.1002/ejoc.201700110

A Journal of
Accepted Article
Title: Three-component one-pot synthesis of unsymmetrical
diarylalkynes via thermo-controlled sequential Sonogashira
reactions using potassium ethynyltrifluoroborate
Authors: Taejung Kim, Kyu Hyuk Jeong, Youngseok Kim, Taesub Noh,
Jaeyoung Choi, and Jungyeob Ham
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201700110
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10.1002/ejoc.201700110
European Journal of Organic Chemistry
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Three-component one-pot synthesis of unsymmetrical
diarylalkynes via thermo-controlled sequential Sonogashira
reactions using potassium ethynyltrifluoroborate
Taejung Kim,[a][‡] Kyu Hyuk Jeong,[a][‡] Youngseok Kim,[a] Taesub Noh,[a,b] Jaeyoung Choi,[a] and
Jungyeob Ham*[a,c]
Abstract: Unsymmetrical diarylalkynes were synthesized in
moderate to good isolated yields through the thermo-controlled
sequential Sonogashira reactions via a three-component one-pot
procedure with potassium ethynyltrifluoroborate and two different
reactive aryl halides. The one-pot procedure was initiated by the
palladium/copper-catalyzed Sonogashira coupling of potassium
ethynyltrifluoroborate to aryl iodides or electron-deficient aryl
bromides proceeded at 40 °C. Following the subsequent deboronative
Sonogashira reaction of the in situ generated potassium
arylethynyltrifluoroborates, a second coupling to less active electron-
rich aryl bromides at 80 °C, without any additional palladium/copper
catalyst or base, gave rise to unsymmetrical diarylalkynes.
2-ol[10] (Scheme 1, C), and ethynylmagnesium bromide[11]
(Scheme 1, D) via Sonogashira coupling. These methods offer a
general synthetic strategy for the construction of bifunctional
C(sp)–C(sp2) bonds that is very useful for hetero-coupled alkyne
derivatives.
Introduction
The reaction between terminal alkynes and aryl and vinyl halides
in the presence of palladium/copper catalysts is known as
SonogashiraHagihara cross-coupling (Sonogashira reaction),
and is one of the most powerful synthetic methods available for
the straightforward construction of C(sp)–C(sp2) bonds.[1] This
method has been used to prepare biologically active small
molecules,[2] natural products,[3] and engineering materials,[4] and
numerous reports have highlighted the utility of this coupling
strategy. Furthermore, methods for the preparation of terminal
alkynes from aldehydes,[5] vicinal-dihaloalkenes,[6] and geminal-
dihaloalkanes[7] have been developed. However, terminal alkynes
are costly and cumbersome materials, have low molecular
weights and boiling points as well as, a short shelf-life (unstable
storage), and are generally difficult to handle. These issues hinder
the widespread use of terminal alkynes as Sonogashira coupling
partners for aryl or vinyl halides.
Scheme
1.
Synthesis
of
unsymmetrical
diarylalkynes
using
ethynyltrimethylsilane (A), propiolic acid (B), 2-methyl-3-butyl-2-ol (C), and
ethynylmagnesium bromide (D).
However, these previous methods for the preparation of the
target biarylalkyne compounds required excess reagents, long
reaction time, high reaction temperature, and step-by-steps
procedure to obtain the unsymmetrical diarylalkynes in
satisfactory yields.
As a solution, several research groups have attempted the
synthesis of alternative alkynes from ethynyltrimethylsilane[8]
(Scheme 1, A), propiolic acid[9] (Scheme 1, B), 2-methyl-3-butyn-
Recently,
the
preparation
of
potassium
alkynylaryltrifluoroborates from haloaryltrifluoroborates via
Sonogashira coupling was successfully demonstrated by our
group.[12] The resulting organotrifluoroborates could be further
functionalized via transformation of the reactive BF3K group.
During the course of our synthetic studies on the development
of novel small molecules from potassium organotrifluoroborates,
we discovered a facile and highly efficient method for the
preparation of unsymmetrical diarylalkynes from the
[a]
Korea Institute of Science and Technology (KIST), 679 Saimdang-
ro, Gangneung 25451, Republic of Korea
Fax: (+82)-33-650-3508; e-mail: ham0606@kist.re.kr
http://gn.kist.re.kr
[b]
[c]
Department of Chemistry, Gangneung-Wonju National University, 7
Jukheon-gil, Gangneung 25457, Republic of Korea
Department of Biological Chemistry, University of Science and
Technology (UST), Gajung-ro 217, Daejeon 34113, Republic of
Korea
corresponding
arylethynyltrifluoroborates.
aryl
halides
with
potassium
[‡]
These authors contributed equally to this work.
Supporting information for this article is given via a link at the end of
the document.
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10.1002/ejoc.201700110
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Table 1. Three-component one-pot synthesis of unsymmetrical diarylalkynes
using potassium ethynyl-trifluoroborate, aryl iodides, and aryl bromides.[a]
Scheme 2. Preparation of unsymmetrical diarylalkynes using potassium
ethynyltrifluoroborate.
Herein, we report the three-component one-pot synthesis of
unsymmetrical
diarylalkynes
from
potassium
ethynyltrifluoroborate[13] and two different reactive aryl halides via
thermo-controlled sequential Sonogashira reactions. To the best
of our knowledge, this is the first report of a three-component one-
pot synthesis of unsymmetrical diarylalkynes from terminal
alkynes generated by in situ deboronation of the potassium
trifluoroborate moiety.
Results and Discussion
Initially, the reaction between potassium ethynyltrifluoroborate, 4-
iodotoluene, and bromobenzene was selected as a model to
optimize the protocol, using our previously reported Sonogashira
reaction conditions.[12] The 1H NMR reaction monitoring between
two
different
reactive
arylhalides
and
potassium
ethynyltrifluoroborate is shown in Scheme 3.
Scheme 3. 1H NMR study of Sonogashira coupling of 4-iodotoluene and
bromobenzene with potassium ethynyltrifluoroborate.
During the first step reaction, the production of potassium 4-
tolylethynyltrifluoroborate (d) was clearly confirmed without side-
product by bromobenzene. When the reaction temperature was
continuously increased from 40 to 80 oC, the desired (4-
methylphenyl)phenylacetylene 4aa was obtained through the
second Sonogashira reaction in 92% yield (Table 1, entry 1).
However, the reacton yield decreased considerably when the
PdCl2(PPh3)2 and CuI was added to 10 mol% due to biphenyl
side-product to be rapidly generated from iodobenzene. Based on
the results, we attempted the thermo-controlled three-component
one-pot synthesis of various unsymmetrical diarylalkynes, using
potassium ethynyltrifluoroborate and two different reactive aryl
halides under Sonogashira conditions. As shown in Table 1.
[a] All reactions were performed on a 2.0 mmol scale in 3.0 mL of DMSO. [b]
Isolated yield based on Ar1-I. [c] 10 mol% of PdCl2(PPh3)2 and 10 mol% of CuI
were used as catalysts. [d] The reaction was performed with 2 equiv of 4-
bromotoluene and potassium ethynyltrifluoroborate. [e] 1,4-bis[2-(4-
methylphenyl)ethynyl]benzene was obtained.
Deboronative
Sonogashira
reaction
of
potassium
arylethynyltrifluoroborates to aryl bromides 3 afforded various
unsymmetrical diarylalkynes 4 in moderate to good yields. When
4-iodotoluene 1a and aryl bromides with electron-donating groups
(4-methoxy 3b, 3,4-dioxole 3c, 3,4-dimethoxy 3d, 3,5-dimethoxy
3e, and 4-hydroxy 3f) were used as starting materials, the desired
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10.1002/ejoc.201700110
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coupling products were obtained in good yields (Table 1, entries
26). Also, we tested the reactivities of o-, m-, and p-
substitutediodotoluenes 1ac and iodobenzotrifluorides 1df
under the same conditions; the yields of the corresponding
products increased in the order of para > meta > ortho (Table 1,
entries 611). Especially, the yields of the corresponding
unsymmetrical diarylalkynes from the deboronative Sonogashira
raction of o-, m-, and p-bromotoluenes 3hj increased in the order
of para > meta ≈ ortho (Table 1, entries 1214). Finally, the use
of mono- or di-iodobenzenes as coupling partners provided the
desired products in 90% and 61% yields, respectively (Table 1,
entries 15 and 16).
Interestingly, when ortho-iodophenol was used as the starting
material, the anticipated product 4ji was not obtained. Instead,
cyclized 4ji was only obtained in 82% yield, owing to the
intramolecular cyclization between the hydroxyl group on the
phenol moiety with the alkyne (Scheme 4).[14] However, when
ortho-iodoaniline was used as the starting material, the indole
formation did not proceed (data not shown).
Subsequently, we examined the synthesis of unsymmetrical
diarylalkynes 6 with two different reactive aryl bromides under the
same conditions (Table 2). As expected, the potassium
arylethynyltrifluoroborate intermediates were readily generated
from the corresponding electron-deficient aryl bromides, and
could be obtained in moderate yields without contamination by
side-products such as symmetrical diarylalkynes or arylalkynes
as intermediates (Table 2, entries 16). Interestingly, 2-
bromonaphthalene and hetero-aryl bromides (2-pyridine 5f, 5-
pyrimidine 5g, and 2-thiophene 5h) were converted into the
corresponding diarylalkynes products in moderate to good yields
(Table 2, entries 710).
Conclusions
Scheme 4. Three-component one-pot reaction of ortho-iodophenol 1j, 1-bromo-
3,4-(methylenedioxy)benzene 3i, and potassium ethynyltrifluoroborate 2.
In summary, a versatile and efficient method for the direct
three-component
diarylalkynes from two different reactive aryl halides and
potassium ethynyltrifluoroborates via thermo-controlled
one-pot
synthesis
of
unsymmetrical
Table 2. Three-component one-pot synthesis of unsymmetric diarylalkynes
using potassium ethynyltrifluoroborate and two different reactive aryl
bromides.[a]
sequential Sonogashira reactions has been developed. This
procedure does not require isolation of the potassium
arylethynyltrifluoroborates or the aryl acetylene intermediates,
and would be particularly useful some reactions to be required
unstable or commercially unavailable aryl alkynes. Further
investigation of the preparation of useful small molecules from
potassium ethynyltrifluorobotate is currently ongoing in our
laboratory.
Experimental Section
General Experimental Details: 1H NMR spectra were recorded on
BRUKER AVANCE 400 spectrometer and the chemical shifts were
reported in parts per million (ppm) relative to internal standard TMS (0
ppm) for CDCl3. The peak patterns are indicated as follows: s, singlet; d,
doublet; bs, broad singlet; dd, doublet of doublet; t, triplet; m, multiplet; q,
quartet. The coupling constants, J, are reported in Hertz (Hz). 13C NMR
spectra were obtained on the same spectrometer and referenced to the
internal solvent signals (central peak is 77.0 ppm in CDCl3). CDCl3 was
used as the NMR solvents. Mass spectrum was determined with 300-MS
(Bruker) for EI-MS. FT-IR spectra were recorded on ATR plate. Flash
column chromatography was performed over silica gel 200-300. All
reagents were weighed and handled in air at room temperature and all
reactions were performed under an air atmosphere. Unless otherwise
noted, all reagents were purchased from commercial suppliers without
further purification.
Experimental Procedures and Analytical Datas:
Typical procedure
I
(Table
1
and Scheme 4) Potassium
ethynyltrifluoroborate (2.0 mmol) was added to a solution of aryl iodide (2.0
mmol), aryl bromide (2.2 mmol), PdCl2(PPh3)2 (0.1 mmol), CuI (0.1 mmol),
piperidine (5.0 mmol), and DMSO (3 mL) under atmospheric conditions.
The reaction mixture was stirred at 40 °C for 3 h. After the Sonogashira
reaction was complete, the temperature of the oil bath was increased to
80 °C, and the solution was stirred further 2 h. After the potassium
[a] All reactions were performed on a 2.0 mmol scale in 3.0 mL of DMSO. [b]
Isolated yield based on Ar1-Br.
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10.1002/ejoc.201700110
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arylethynyltrifluoroborate intermediate was consumed, the reaction
mixture was diluted with acetone (10 mL), filtered through a Celite pad,
concentrated, and purified by chromatography.
1520, 1487, 1405, 1187, 1129, 1105, 1066, 1019, 842, 701, 689 cm-1. EI-
MS: m/z calcd for C15H9F3 [M]+ 246.23, found 246.10.
1-(phenylethynyl)-3-(trifluoromethyl)benzene (4eg) mp = 36.6-37.8 oC.
1H NMR (400 MHz, CDCl3) δ 7.80 (s, 1H), 7.70 (d 1H, J = 7.8 Hz), 7.59-
7.52 (m, 3H), 7.48 (t, 2H, J = 7.8 Hz), 7.39-7.35 (m, 3H). 13C NMR (100
MHz, CDCl3) δ 134.6, 132.5, 131.7, 130.9 (q, J = 32.0 Hz), 129.2, 128.9,
128.7, 128.4 (q, J = 3.7 Hz), 124.7 (q, J = 3.7 Hz), 124.2, 122.6, 90.9, 87.8
FT-IR (ATR): 3063, 2359, 1493, 1429, 1336, 1290, 2169, 1166, 1123,
1092, 1069, 900, 889, 799, 753, 707, 687, 657 cm-1. EI-MS: m/z calcd for
C15H9F3 [M]+ 246.23, found 246.10.
o
1-methyl-4-(phenylethynyl)benzene (4aa) mp = 71.2-72.5 C. 1H NMR
(400 MHz, CDCl3) δ 7.53-7.51 (m, 2H), 7.43 (dd, 2H, J = 6.3, 1.8 Hz), 7.34-
7.32 (m, 3H), 7.14 (d, 2H, J = 7.8 Hz), 2.37 (s, 3H). 13C NMR (100 MHz,
CDCl3) δ 138.4, 131.6, 131.5, 129.1, 128.3, 128.1, 123.5, 120.2, 89.6, 88.7,
21.5. FT-IR (ATR): 3050, 3030, 2918, 1594, 1508, 1484, 1440, 1106, 1070,
1025, 915, 817, 753, 709, 689 cm-1. EI-MS: m/z calcd for C15H12 [M]+
192.26, found 192.10.
1-methoxy-4-(p-tolylethynyl)benzene (4ab) mp = 73.1-74.3 oC. 1H NMR
(400 MHz, CDCl3) δ 7.48-7.44 (m, 2H), 7.40 (d, 2H, J = 8.0 Hz), 7.14 (d,
2H, J = 7.8 Hz), 6.88-6.86 (m, 2H), 3.82 (s, 3H), 2.36 (s, 3H). 13C NMR
(100 MHz, CDCl3) δ 159.5, 138.0, 132.9, 131.3, 129.1, 120.5, 115.4, 113.9,
88.6, 88.2, 55.3, 21.5. FT-IR (ATR): 2919, 1605, 1567, 1463, 1301, 1287,
1248, 1175, 1136, 1106, 1030, 832, 818, 752 cm-1. EI-MS: m/z calcd for
C16H14O [M]+ 222.29, found 222.20.
1-(phenylethynyl)-2-(trifluoromethyl)benzene (4fg) Oil type. 1H NMR
(400 MHz,CDCl3) δ 7.70 (t, 2H, J = 7.3 Hz), 7.59-7.54 (m, 2H), 7.51(d, 1H
J = 8.2 Hz), 7.44 (d, 1H, J = 7.1 Hz), 7.37-7.35 (m, 3H). 13C NMR (100
MHz, CDCl3) δ 133.7, 131.7, 131.4, 128.8, 128.4, 127.9, 126.0, 125.9,
125.88, 125.83, 125.0, 122.7, 122.2, 121.6, 94.9, 85.3 FT-IR (ATR): 3064,
2359, 2222, 1683, 1604, 1573, 1496, 1319, 1311, 1171, 1129, 1109, 1055,
1031, 754, 688, 669 cm-1. EI-MS: m/z calcd for C15H9F3 [M]+ 246.23, found
246.10.
5-(p-tolylethynyl)benzo[d][1,3]dioxole (4ac) mp = 128.2-129.8 oC. 1H
NMR (400 MHz, CDCl3) δ 7.39 (d, 2H J = 8.3 Hz), 7.14 (d, 2H, J = 8.0 Hz),
7.05 (dd, 1H, J = 8.0, 1.5 Hz), 6.98 (d, 1H, J = 1.5 Hz), 6.78 (d, 1H J = 8.0
Hz), 5.98 (s, 2H), 2.36 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 147.7, 147.4,
138.2, 131.3, 129.1, 127.7, 126.1, 120.2, 116.7, 111.5, 108.4, 101.3, 88.6,
87.9, 21.5. FT-IR (ATR): 2958, 2918, 2358, 2330, 1692, 1500, 1488, 1442,
1388, 1252, 1229, 1145, 1040, 942, 810 cm-1. EI-MS: m/z calcd for
C16H12O [M]+ 236.27, found 236.20.
1-methoxy-4-(p-tolylethynyl)benzene (4gh) mp = 115.3-119.7 oC. 1H
NMR (400 MHz, CDCl3) δ 7.48-7.44 (m, 4H), 7.14 (d, 2H, J = 7.8 Hz), 6.89-
6.85 (m, 2H), 3.83 (s, 3H), 2.36 (s, 3H). 13C NMR (100 MHz, CDCl3) δ
159.5, 138.0, 133.0, 131.3, 129.1, 120.5, 115.6, 114.0, 88.6, 88.2, 55.3,
21.5. FT-IR (ATR): 2919, 2218, 1726, 1602, 1510, 1462, 1285, 1245, 1171,
1135, 1028, 831, 816, 798 cm-1. EI-MS: m/z calcd for C16H14O [M]+ 222.29,
found 222.20.
1,2-dimethoxy-4-(p-tolylethynyl)benzene (4ad) mp = 92.4-93.5 oC. 1H
NMR (400 MHz, CDCl3) δ 7.41 (d, 2H, J = 8.0 Hz), 7.16-7.11 (m, 3H), 7.03
(d, 1H J = 2.0 Hz), 6.83 (d, 1H, J = 8.5 Hz), 3.90 (d, 6H, J = 6.8 Hz), 2.36
(s, 3H). 13C NMR (100 MHz, CDCl3) δ 149.3, 148.6, 138.1, 131.3, 129.1,
124.8, 120.3, 115.7, 114.2, 111.1, 88.7, 88.1, 55.9, 21.5. FT-IR (ATR):
2918, 1597, 1516, 1463, 1441, 1327, 1271, 1249, 1228, 1139, 1123, 1025,
815, 764 cm-1. EI-MS: m/z calcd for C17H16O2 [M]+ 252.31, found 252.20.
1-((4-methoxyphenyl)ethynyl)-3-methylbenzene (4gi) mp = 42.6-43 oC.
1H NMR (400 MHz, CDCl3) δ 7.48-7.45 (m, 2H), 7.35 (s, 1H), 7.32 (d, 1H,
J = 7.8 Hz), 7.23 (t, 1H, J = 7.8 Hz), 7.12 (d, 1H, J = 7.0 Hz), 6.90-6.86 (m,
2H), 3.83 (s, 3H), 2.35 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 159.5, 138.0,
134.1, 133.0, 132.0, 128.8, 128.5, 128.2, 123.4, 115.5, 115.5, 114.1, 114.0,
89.0, 88.2, 55.3, 21.2. FT-IR (ATR): 2918, 2357, 2201, 1596, 1508, 1302,
1286, 1245, 1172, 1105, 1030, 829, 809, 782, 689cm-1. EI-MS: m/z calcd
for C16H14O [M]+ 222.29, found 222.20.
1,3-dimethoxy-5-(p-tolylethynyl)benzene (4ae) mp = 81.0-84.1 oC. 1H
NMR (400 MHz, CDCl3) δ 7.42 (d, 2H, J = 8.0 Hz), 7.15 (d, 2H, J = 7.8 Hz),
6.68 (d, 2H, J = 2.3 Hz), 6.45 (t, 1H, J = 4.5 Hz), 3.80 (s, 6H), 2.36 (s, 3H).
13C NMR (100 MHz, CDCl3) δ 160.5, 138.5, 131.5, 129.1, 124.7, 120.0,
109.3, 101.7, 89.1, 88.7, 55.4, 21.5. FT-IR (ATR): 2958, 2918, 2362, 1587,
1511, 1453, 1420, 1359, 1255, 1239, 1205, 1156, 1064, 926, 844, 815 cm-
1. EI-MS: m/z calcd for C17H16O2 [M]+ 252.31, found 252.20.
1-((4-methoxyphenyl)ethynyl)-2-methylbenzene (4gj) mp
= 73.0-
74.3oC. 1H NMR (400 MHz, CDCl3) δ 7.50-7.46 (m, 3H), 7.24-7.20 (m, 2H),
7.19-7.14 (m, 1H), 6.90-6.87 (m, 2H), 3.84 (s, 3H), 2.51 (s,3H). 13C NMR
(100 MHz, CDCl3) δ 159.6 139.9, 134.1, 131.7, 132.9, 129.4, 127.9, 125.5,
123.3, 115.7, 114.0, 93.3, 87.0, 55.3, 20.7. FT-IR (ATR): 2960, 2359, 1602,
1507, 1481, 1286, 1245, 1184, 1172, 1030, 831, 819, 801, 754, 717 cm-1.
EI-MS: m/z calcd for C16H14O [M]+ 222.29, found 222.10.
4-(p-tolylethynyl)phenol (4af) mp = 97.0-98.1 oC. 1H NMR (400 MHz,
CDCl3) δ 7.42-7.39 (m, 4H), 7.14 (d, 2H, J = 8.0 Hz), 6.82-6.78 (m, 2H),
2.36 (s, 3H,). 13C NMR (100 MHz, CDCl3) δ 155.5, 138.1, 133.2, 131.3,
129.1, 120.4, 115.9, 115.5, 88.5, 88.2, 21.5. FT-IR (ATR): 3532, 3220,
2361, 1607, 1514, 1453, 1256, 1103, 833, 819 cm-1. EI-MS: m/z calcd for
C15H12O [M]+ 208.26, found 208.20.
1,2-diphenylethyne (4hg) mp = 50.2-51.5 oC. 1H NMR (400 MHz, CDCl3)
δ 7.55-7.52 (m, 4H), 7.38-7.31 (m, 6H). 13C NMR (100 MHz, CDCl3) δ
131.6, 128.3, 128.2, 123.3, 89.3. FT-IR (ATR): 3063, 2359, 1599, 1493,
1442, 1312, 1070, 1026, 917, 755, 688, 668 cm-1. EI-MS: m/z calcd for
C14H10 [M]+ 178.23, found 178.10.
1-methyl-3-(phenylethynyl)benzene (4bg) Oil type. 1H NMR (400 MHz,
CDCl3) δ 7.54-7.51 (m, 2H), 7.37-7.33 (m, 5H), 7.22 (d, 1H, J = 7.5 Hz),
7.15 (d, 1H, J = 7.8 Hz), 2.36 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 138.0,
132.2, 131.6, 129.2, 128.7, 128.3, 128.25, 128.18, 123.4, 123.1, 89.6, 89.1,
21.3. FT-IR (ATR): 3055, 2359, 1601, 1492, 1442, 1069, 1026, 911, 781,
753, 687 cm-1. EI-MS: m/z calcd for C15H12 [M]+ 192.26, found 192.10.
1,4-bis(p-tolylethynyl)benzene (4ih) mp = 156.0-160.1 oC. 1H NMR (400
MHz, CDCl3) δ 7.49 (s, 4H), 7.42 (d, 4H, J = 8.0 Hz), 7.16 (d, 4H, J = 8.0
Hz), 2.37 (s, 6H). 13C NMR (100 MHz, CDCl3) δ 138.6, 131.5, 131.4, 129.1,
123.1, 120.0, 91.3, 88.5, 29.7, 21.5. FT-IR (ATR): 2920, 2851, 1727, 1272,
1120, 1072, 838, 816, 756, 708 cm-1. EI-MS: m/z calcd for C24H18 [M]+
306.41, found 306.20.
1
1-methyl-2-(phenylethynyl)benzene (4cg) Oil type H NMR (400 MHz,
5-(benzofuran-2-yl)benzo[d][1,3]dioxole (cyclized 4ji) mp = 101.9-
1
CDCl3) δ 7.55-7.53 (m, 2H), 7.49 (d, 1H, J = 7.3 Hz), 7.36-7.34 (m, 3H),
7.23 (d, 2H, J = 4.0 Hz), 7.19-7.15 (m, 1H), 2.52 (s, 3H) 13C NMR (100
MHz, CDCl3) δ 140.2, 131.8, 131.5, 129.5, 128.4, 128.3, 128.2, 125.6,
123.5, 123.0, 93.3, 88.3, 20.7 FT-IR (ATR): 3058, 2359, 1600, 1492, 1455,
1441, 1157, 1069, 1041, 751, 714, 688 cm-1. EI-MS: m/z calcd for C15H12
[M]+ 192.26, found 192.10.
103.3 oC. H NMR (400 MHz, CDCl3) δ 7.57-7.54 (m, 2H), 7.51-7.48 (m,
2H), 7.40 (dd, 1H, J = 8.0, 2.0 Hz), 7.32 (d, 1H, J = 2.0 Hz), 7.24 (dt, 2H,
J = 18.8, 1.2 Hz), 6.89 (d, 1H, J = 8.0 Hz), 6.87 (d, 1H, J = 0.8 Hz), 6.02
(s, 2H). 13C NMR (100 MHz, CDCl3) δ 155.8, 154.7, 148.1, 148.0, 129.3,
124.8, 123.9, 122.9, 120.7, 119.2, 111.0, 108.7, 105.5, 101.3, 100.2. FT-
IR (ATR): 3352, 2903, 1500, 1486, 1471, 1451, 1284, 1253, 1232, 1041,
931, 797, 748, 736 cm-1. EI-MS: m/z calcd for C15H10O3 [M]+ 238.06, found
238.10.
1-(phenylethynyl)-4-(trifluoromethyl)benzene (4dg) mp = 102.8-103.5
oC. 1H NMR (400 MHz, CDCl3) δ 7.62 (d, 2H, J = 8.5 Hz), 7.58 (d, 2H J =
8.8 Hz), 7.56-7.54 (m, 2H), 7.38-7.36 (m, 3H). 13C NMR (100 MHz, CDCl3)
δ 131.8, 131.7, 129.9 (q, J = 32.6 Hz), 128.8, 128.4, 127.2, 127.1, 125.3,
(q, J = 3.7 Hz), 122.6, 91.7, 87.9. FT-IR (ATR): 2221, 1683, 1609, 1571,
Typical procedure II (Table 2) Potassium ethynyltrifluoroborate (2.0
mmol) was added to a solution of an electron-deficient aryl bromide (or
naphtyl and hetero-aryl bromide) (2.0 mmol), bromobenzene (or electron-
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10.1002/ejoc.201700110
European Journal of Organic Chemistry
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rich aryl bromide) (2.2 mmol), PdCl2(PPh3)2 (0.1 mmol), CuI (0.1 mmol),
piperidine (5.0 mmol), and DMSO (3 mL) under atmospheric conditions.
The reaction mixture was stirred at 40 °C for 3 h. After the Sonogashira
reaction was complete, the temperature of the oil bath was increased to
80 °C, and the solution was stirred further 2 h. After the potassium
arylethynyltrifluoroborate intermediate was consumed, the reaction
mixture was diluted with acetone (10 mL), filtered through a Celite pad,
concentrated, and purified by chromatography.
5-(phenylethynyl)pyrimidine (6ga) mp = 43.1-44.9 oC. 1H NMR (400
MHz, CDCl3) δ 9.15 (s, 1H), 8.87 (s, 2H), 7.57-7.55 (m, 2H), 7.42-7.36 (m,
3H). 13C NMR (100 MHz, CDCl3) δ 158.6, 156.7, 131.8, 129.4, 128.5,
121.8, 120.0, 96.3, 82.3. FT-IR (ATR): 2920, 2220, 1541, 1491, 1413,
1183, 1163, 907, 755, 171, 688 cm-1. EI-MS: m/z calcd for C12H8N2 [M]+
180.21, found 180.10.
2-(phenylethynyl)thiophene (6ha) mp = 45.9-48.8 oC. 1H NMR (400 MHz,
CDCl3) δ 7.55-7.51 (m, 2H), 7.36-7.33 (m, 3H), 7.31-7.27 (m, 2H), 7.03-
7.00 (m, 1H). 13C NMR (100 MHz, CDCl3) δ 131.9, 131.4, 128.4, 128.4,
128.3, 127.6, 127.2, 122.9, 93.0, 82.6. FT-IR (ATR): 3097, 2359, 1517,
1485, 1212, 1197, 110, 1037, 851, 829, 754, 700, 686 cm-1. EI-MS: m/z
calcd for C12H8S [M]+ 184.26, found 184.10.
1-(phenylethynyl)-4-(trifluoromethyl)benzene (6aa) mp = 102.8-103.5
oC. 1H NMR (400 MHz, CDCl3) δ 7.62 (d, 2H, J = 8.5 Hz), 7.58 (d, 2H J =
8.8 Hz), 7.56-7.54 (m, 2H), 7.38-7.36 (m, 3H). 13C NMR (100 MHz, CDCl3)
δ 131.8, 131.7, 129.9 (q, J = 32.6 Hz), 128.8, 128.4, 127.2, 127.1, 125.3,
(q, J = 3.7 Hz), 122.6, 91.7, 87.9. FT-IR (ATR): 2221, 1683, 1609, 1571,
1520, 1487, 1405, 1187, 1129, 1105, 1066, 1019, 842, 701, 689 cm-1. EI-
MS: m/z calcd for C15H9F3 [M]+ 246.23, found 246.10.
Acknowledgements
1-methoxy-4-((4-(trifluoromethyl)phenyl)ethynyl)benzene (6ab) mp =
97.4-98.1 oC. 1H NMR (400 MHz, CDCl3) δ 7.60 (t, 4H J = 9.3 Hz), 7.51-
7.47 (m, 2H), 6.92-6.88(m, 2H), 3.84 (s, 3H). 13C NMR (100 MHz, CDCl3)
δ 160.0, 133.3, 131.6, 129.5 (q, J = 33 Hz), 125.2 (d, J = 3 Hz), 124,0 (q,
J = 272 Hz), 114.6, 114.1, 91.9, 86.8, 55.3. FT-IR (ATR): 2217, 1600, 1521,
1503, 1319, 1290, 1251, 1164, 1122, 1103, 1065, 1030, 839, 824, 791,
672 cm-1. EI-MS: m/z calcd for C16H11F3O [M]+ 276.26, found 276.10.
This work was supported by the Korea Institute of Science and
Technology (KIST) institutional program (Project No. 2Z04930).
This research was also conducted under the industrial
infrastructure program for fundamental technologies (N0000885)
which is funded by the Ministry of Trade, Industry & Energy
(MOTIE, Korea).
1-methyl-4-((4-(trifluoromethyl)phenyl)ethynyl)benzene (6ah) mp =
142.9-143.2 oC. 1H NMR (400 MHz, CDCl3) δ 7.63-7.58 (m, 4H), 7.44 (d,
2H, J = 8.0 Hz), 7.18 (d, 2H, J = 7.8 Hz), 2.38 (s, 3H). 13C NMR (100 MHz,
CDCl3) δ 139.1, 131.7, 131.6, 129.7 (q, J = 33 Hz), 129.2, 127.3, 125.2 (q,
J = 4.0 Hz), 124.0 (q, J = 272 Hz), 119.5, 92.0, 87.4, 21.5. FT-IR (ATR):
2218, 1325, 1169, 1136, 1121, 1105, 1067, 1015, 842, 820, 755, 669 cm-
1. EI-MS: m/z calcd for C16H11F3 [M]+ 260.26, found 260.10.
Keywords: potassium ethynyltrifluoroborate • Sonogashira
reaction • Three-component one-pot synthesis • Unsymmetrical
diarylalkynes
4-(phenylethynyl)benzonitrile (6ba) mp = 112.5-112.8 oC. 1H NMR (400
MHz, CDCl3) δ 7.65-7.59 (m, 4H), 7.56-7.53 (m, 2H), 7.40-7.37 (m, 3H).
13C NMR (100 MHz, CDCl3) δ 132.0, 131.8, 129.1, 128.5, 128.2, 122.2,
118.5, 111.5, 93.8, 87.7, 29.7. FT-IR (ATR): 2923, 2227, 1603, 1502, 1485,
1442, 1158, 1134, 1070, 1025, 967, 842, 759, 690 cm-1. EI-MS: m/z calcd
for C15H9N [M]+ 203.24, found 203.10.
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methyl 4-(phenylethynyl)benzoate (6ca) mp = 115.6-116.7 oC. 1H NMR
(400 MHz, CDCl3) δ 8.02 (d, 2H, J = 8.4 Hz), 7.61-7.58 (m, 2H), 7.56-7.53
(m, 2H), 7.39-7.35 (m, 3H), 3.93 (s, 3H). 13C NMR (100 MHz, CDCl3) δ
166.6, 131.7, 131.5, 129.5, 129.4, 128.7, 128.4, 128.0, 122.7, 92.3, 88.6,
52.2. FT-IR (ATR): 2948, 2217, 1709, 1604, 1454, 1436, 1309, 1276, 1192,
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(400 MHz, CDCl3) δ 7.94 (d, 2H, J = 8.4 Hz), 7.61 (d, 2H, J = 8.4 Hz), 7.57-
7.54 (m, 2H), 7.38-7.36 (m, 3H), 2.62 (s, 3H). 13C NMR (100 MHz, CDCl3)
δ 197.3, 136.2, 131.8, 131.7, 128.8, 128.4, 128.3, 128.2 122.6, 92.7, 88.6,
26.6. FT-IR (ATR): 3000, 2218, 1676, 1601, 1485, 1433, 1404, 1303, 1285,
1263, 1179, 1141, 860, 834, 759, 691 cm-1. EI-MS: m/z calcd for C16H12O
[M]+ 220.27, found 220.10.
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8.63 (s, 1H), 7.71-7.66 (m, 1H), 7.63-7.58 (m, 2H), 7.53 (d, 1H, J = 7.8 Hz),
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Entry for the Table of Contents
SHORT COMMUNICATION
C-C Bond Formation*
Taejung Kim,‡ Kyu Hyuk Jeong,‡
Youngseok Kim, Taesub Noh, Jaeyoung
Choi, and Jungyeob Ham*
Page No. – Page No.
Unsymmetrical diarylalkynes were synthesized in moderate to good isolated yields
through the thermo-controlled sequential Sonogashira reactions via a three-
component one-pot procedure with potassium ethynyltrifluoroborate and two
different reactive aryl halides.
Three-component one-pot synthesis
of unsymmetrical diarylalkynes via
thermo-controlled sequential
Sonogashira reactions using
potassium ethynyltrifluoroborate
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