Copper-catalyzed direct synthesis of furans and thiophenes via decarboxylative coupling of alkynyl carboxylic acids with H2O or Na2S

Article abstract of DOI:10.1016/j.tet.2015.05.017

2,5-Diaryl-substituted furans were synthesized from the copper-catalyzed decarboxylative coupling of aryl-substituted aryl propiolic acids in the presence of H₂O. The homocoupling of alkynyl carboxylic acids provided 1,4-diaryldiynes, which then reacted with H₂O to give the desired furans through cyclization. Addition of the copper catalyst was critical, and the addition of a ligand increased the yield of products in both the homocoupling and cyclization reactions. In addition, thiophenes could be obtained when the reaction was conducted in the presence of Na₂S.

Full text of DOI:10.1016/j.tet.2015.05.017

Accepted Manuscript
Copper-Catalyzed Direct Synthesis of Furans and Thiophenes via Decarboxylative
Coupling of Alkynyl Carboxylic Acids with H O or Na S
2
2
Francis Mariaraj Irudayanathan, Gabriel Charles Edwin Raja, Sunwoo Lee
PII:
S0040-4020(15)00660-2
10.1016/j.tet.2015.05.017
TET 26734
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 15 January 2015
Revised Date: 6 May 2015
Accepted Date: 6 May 2015
Please cite this article as: Irudayanathan FM, Edwin Raja GC, Lee S, Copper-Catalyzed Direct
Synthesis of Furans and Thiophenes via Decarboxylative Coupling of Alkynyl Carboxylic Acids with H O
2
or Na S, Tetrahedron (2015), doi: 10.1016/j.tet.2015.05.017.
2
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ACCEPTED MANUSCRIPT
Copper-Catalyzed Direct Synthesis of Furans and Thiophenes via Decarboxylative
Coupling of Alkynyl Carboxylic Acids with H2O or Na2S
Francis Mariaraj Irudayanathan, Gabriel Charles Edwin Raja, Sunwoo Lee*
Department of Chemistry, Chonnam National University, Gwangju 500-757, Republic of
Korea
Corresponding Author : sunwoo@chonnam.ac.kr
Keywords : furan, thiophene, copper, decarboxylative coupling, propiolic acids

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Graphic Abstract

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Abstract
2,5-Diaryl-substituted furans were synthesized from the copper-catalyzed decarboxylative
coupling of aryl-substituted aryl propiolic acids in the presence of H2O. The homocoupling of
alkynyl carboxylic acids provided 1,4-diaryldiynes, which then reacted with H2O to give the
desired furans through cyclization. Addition of the copper catalyst was critical, and the
addition of a ligand increased the yield of products in both the homocoupling and cyclization
reactions. In addition, thiophenes could be obtained when the reaction was conducted in the
presence of Na2S.

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1. Introduction
Decarboxylative coupling reactions of alkynyl carboxylic acids are useful methods for the
formation of sp carbon bonds with various coupling partners.1 As alkynyl sources, alkynyl
carboxylic acids have several advantages in that they are stable and release non-toxic CO2
after coupling. Since we first reported the palladium-catalyzed decarboxylative coupling
reaction of propiolic acid and aryl halides,2 a number of related methodologies have been
developed by our group and others.3 Palladium and other metals such as copper, nickel, and
silver have been employed as catalysts.4 In addition, many multicomponent reactions with
alkynyl carboxylic acids have been developed to provide cyclized organic compounds such as
imidazopyridine, isocoumarine, and isoindolinone.5
Recently, we reported the direct synthesis of 1,4-diaryl-1,3-diynes via the coupling reaction
of aryl iodide with propiolic acid and its sequential homocoupling.6 As part of our ongoing
efforts to develop decarboxylative coupling reactions, we were interested in the direct
synthesis of furans from the decarboxylative homocoupling of alkynyl carboxylic acids and
the sequential cyclization.
Furans serve as important building blocks in organic synthesis. Many natural compounds, as
well as organic products of significant medicinal and material importance, are prepared from
furan precursors.7 In particular, 2,5-diarylsubstituted furan derivatives can act as
antimicrobial agents and enzyme inhibitors, as shown in Fig. 1.8

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Fig. 1. Some biologically active 2,5-diarylfuran derivatives.
A number of synthetic routes toward 2,5-diarylsubstituted furans have been reported. For
example, the cyclization reactions of 1,4-diarylbutane-1,4-dione,9 1,4-diaryl-2-butyne-1,4-
dione,10 and 4-oxo-1,4-diarylbut-2-enyl acetate11 are commonly used in the synthesis of 2,5-
diarylsubstituted furans, as shown in Schemes 1a, 1b, and 1c, respectively. However, these
methods have some drawbacks, including need for preparation of the starting materials,
limited substrate scope, and harsh conditions. As an alternative, 1,4-diaryl-1,3-butyne and
alkynyl bromide were employed as starting materials, which provided the desired products
through cyclization, as shown in Scheme 1d and 1e.12 Although these methods were
applicable to a broad range of substrates, multistep syntheses were still required to prepare
the starting materials.
To address these issues, we attempted to develop a direct synthetic route to 2,5-
diarylsubstituted furans from aryl alkynyl carboxylic acids. Our method has several
advantages. Specifically, the isolation of 1,4-diaryl-1,3-diyne intermediates is not required.
Moreover, the preparation of aryl alkynyl carboxylic acids via the coupling of aryl halides
and propiolic acid is simple and easy.13 Herein, we report the copper-catalyzed synthesis of
furan derivatives from alkynyl carboxylic acids and H2O.

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Scheme 1. Synthetic methods used to prepare 2,5-diarylsubstituted furans.
2. Results and Discussion
To accomplish the one-pot sequential synthesis of furans, phenyl propiolic acid was chosen as
a model substrate and the reaction was conducted with H2O under a variety of conditions.
Table 1. Screening of reaction conditions for one-pot synthesis of 2a from 1a.a
Ligands
t-Bu
t-Bu
CO2H
NH
N
N
N
N
N
N
N
N
Me
Me
L5
L4
L2
L3
L1
Entry
Catalyst
Pd(PPh3)2Cl2
Pd(OAc)2
Pd(PPh3)4
Cu(OAc)2
CuBr
Ligand
Base
Yield (%)b
1
2
3
4
5
6
7
-
-
-
-
-
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
-
-
-
9
7
CuI
CuI
-
L1
15
44

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8
9
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuIc
K2CO3
K2CO3
K2CO3
K2CO3
Cs2CO3
Na2CO3
DBU
41
89
34
67
56
61
23
15
49
L2
L3
L4
L5
L3
L3
L3
L3
L3
10
11
12
13
14
15
16
Et3N
K2CO3
aReaction conditions : 1a (0.3 mmol), catalyst (0.03 mmol), ligand (0.06 mmol), KOH (1.5
mmol) and base (0.6 mmol) were reacted in DMSO (1.0 mL) at 100 C for 12 h. Isolated
yield. cCuI (0.015 mmol) was used.
o
b
Using K2CO3 / KOH as bases and DMSO as a solvent, we first tested a variety of catalysts.
When the reaction was conducted in the presence of palladium catalysts, the desired product
was not formed (entries 1-3). Upon changing the catalyst to copper, the desired product was
formed; however, all the tested copper sources such as Cu(OAc)2, CuBr, and CuI resulted in
very low yields (9-15% yield; entries 4-6). To increase the yield of the product, we employed
amine-based ligands. When the reactions were carried out with 2,2-bipyridine (L1) and 4,4’-
di-tert-butyl-2,2’-bipyridyl (L2), the yield of the product was increased to 44% and 41%,
respectively (entries 7 and 8). The reaction with 1,10-phenanthroline (L3) afforded the
desired furan in 89% yield (entry 9). However, the sterically demanding ligand L4 resulted in
only 34% yield of the product (entry 10). L-Proline (L5) did not give satisfactory results
(entry 11). Using CuI and 1,10-phenanthroline, other bases were tested in the reaction.
Cs2CO3 and Na2CO3 provided the desired product in 56% and 61% yield, respectively
(entries 12 and 13). Organic bases such as DBU and Et3N resulted in low yields (23 and 15%
yield; entries 14 and 15). When the amount of CuI was reduced to 5 mol%, the desired
product was formed with 49% yield (entry 16).
Based on these results, the optimized conditions were set as follows: 10 mol% CuI and 20
mol% 1,10-phenanthroline in the presence of KOH (5.0 equivalents), K2CO3 (2 equivalents)
and H2O (5.0 equivalents)14 in DMSO at 100 oC for 12 h.

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With the optimized conditions in hand, we evaluated the scope of viable aryl alkynyl
carboxylic acids; the results are summarized in Fig. 2. As expected, phenyl propiolic acid
(1a) provided the desired furan 2a in 89% isolated yield. Alkyl-substituted phenyl propiolic
acids gave the corresponding furans 2b, 2c, 2d, 2e, and 2f in 74%, 72%, 85%, 81%, and 88%
yields, respectively. 4-Methoxy and 2-methoxy phenyl propiolic acids were transformed into
2g and 2h in 76% and 79% yields, respectively. Chloro- or fluoro-substituted phenyl
propiolic acids also resulted in good product yields. 4-Trifluoromethylphenyl propiolic acid
afforded the desired furan 2l in 73% yield. 3-(Thiophen-2-yl)propiolic acid afforded 2m in a
good yield. 1-Naphthalenyl propiolic acid afforded the desired furan 2n in 69% yield.

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10 mol% CuI
O
20 mol% 1,10-Phen
Ar
Ar
Ar
CO2H
K2CO3 (2.0 eq) / KOH (5.0eq.)
2
H2O (5.0 eq.)
DMSO / 100 oC, 12 h
1
Me Me
O
O
2a (89%)
O
2b (74%)
Me
Me
O
Me
Me
2c (72%)
2d (85%)
Me
Me
Me
Me
Et
Et
O
O
2f (88%)
2e (81%)
OMe MeO
MeO
OMe
Cl
O
O
2g (76%)
2h (79%)
Cl
O
O
Cl
Cl
2j (67%)
2i (64%)
F
F
F3C
CF3
O
O
2l (73%)
2k (71%)
S
S
O
O
2n (69%)
2m (72%)
Fig. 2. Copper-catalyzed one-pot synthesis of 2,5-diarylsubstituted furans.
Next, we studied the reaction pathway and the role of the ligand and base in the synthesis of

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2,5-diarylfurans (Scheme 2). When phenyl propiolic acid (1a) was reacted with CuI in the
absence of H2O, the homocoupling product 1,4-diphenyl-1,3-butadiyne (3a) was formed
without concomitant formation of 2,5-diphenylfuran (2a). The yield was 97% in the presence
of the ligand, while the yield was 65% in the absence of the ligand. In the reaction between
1,4-diphenyl-1,3-butadiyne (3a) and H2O in the presence of CuI, the yield of 2,5-
diphenylfuran (2a) was the greatest in the presence of both the ligand and the base; the yield
of the product decreased to 70% in the absence of the ligand. No product was formed without
the addition of the ligand or base. From these results, we postulated that phenyl propiolic acid
(1a) was transformed to 1,4-diphneyl-1,3-butadiyne (3a) through decarboxylative
homocoupling and the resulting product reacted with H2O to produce the desired furan. We
found that the addition of the copper catalyst and the ligand was critical as it increased the
yields of the products in both the homocoupling and cyclization reactions.
10 mol% CuI
(eq 1)
Ph
Ph
Ph
CO2H
K2CO3 (2.0 eq)
3a
1a
DMSO
100 oC, 12 h
with ligand : 97 % yield
without ligand : 65 % yield
O
10 mol% CuI
Ph
Ph
(eq 2)
Ph
Ph
KOH (5.0 eq.) / H2O (5.0 eq.)
DMSO / 100 oC, 5 h
3a
2a
CuI
ligand
Base
2a (yield)
w
w
w
w
90%
0%
w/o
w/o
w
w
w/o
w/o
w
70%
w/o
w
w/o
w/o
0%
0%
w = with, w/o = without
Scheme 2. Studies regarding the role of copper and the ligand.

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The success of the one-pot synthesis of oxygen-containing heterocyclic compounds prompted
us to extend the methodology to the synthesis of other heterocyclic compounds bearing sulfur
or nitrogen. In place of H2O, when Na2S.9H2O was employed in the reaction with phenyl
propiolic acid under the optimized conditions, the desired thiophene 4a was formed in only
5% yield. However, after the homocoupling of phenyl propiolic acid 1a, the sequential
addition of Na2S resulted in a better yield than that observed in the one-pot reaction. When
NaSH and H2S (in MeOH) were employed, no desired product was formed. Accordingly, the
sequential addition was employed in the synthesis of diaryl substituted thiophenes, as shown
in Figure 3. Phenyl propiolic acid 1a provided the desired product 4a in 68% yield. Alkyl-
substituted phenyl propiolic acids like 4-methyl phenyl propiolic acid and 3,4 dimethyl
phenyl propiolic acid gave the corresponding thiophenes 4d and 4e in 71% and 75% yields,
respectively. 1-Naphthylpropiolic acid provided the desired product 4n in 64% yield. Para-
fluorophenyl propiolic acid resulted in a low yield of thiophene 4m.

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Fig. 3. Sequential synthesis of thiophenes.
3. Conclusion
In summary, we developed a one-pot synthesis of 2,5-diarylsubstituted furans from the
homocoupling and cyclization of aryl alkynyl carboxylic acids. This is the first report for the
synthesis of diaryl furans via decarboxylative coupling. The by-product is CO2, with high
conversion and selectivity of the product, and the simple isolation procedure makes the
process environmentally benign. Aryl alkynyl carboxylic acids are stable and easily prepared
from the coupling reaction of propiolic acid and aryl halides. Intermediates such as 1,4-
diaryl-1,3-butadiyne do not need to be isolated. Further, the reaction showed a broad
substrate scope. In addition, thiophenes could be synthesized under the optimized conditions
via the sequential addition of Na2S.9H2O.
4. Experimental Section

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4.1. General
All reagents and solvents were purchased and used without further purification. Analytical
thin layer chromatography (TLC) was performed on TLC silica gel 60 F254. The TLC plates
were visualized by shortwave (254 nm) or long-wave (360 nm) UV light. Flash
chromatography on silica gel (230–400 mesh) was performed. Melting points were
1
determined on a capillary melting point apparatus and are uncorrected. H NMR (300 and
600 MHz) and 13C NMR (75 and 151 MHz) spectra were recorded in CDCl3. Chemical shifts
are given in parts per million (ppm) downfield from tetramethylsilane (TMS) as an internal
1
reference and coupling constants (J-values) are in hertz (Hz). H NMR assignment
abbreviations are the following; singlet (s), doublet (d), triplet (t), quartet (q), broad singlet
(bs), doublet of doublets (dd), triplet of doublets (td), doublet of a triplets (dt) and multiplet
(m).
4.1. General procedure for synthesis of 2,5-disubstituted furans:
Phenyl propiolic acid 1a (439 mg, 3.0 mmol), K2CO3 (830 mg, 6.0 mmol), KOH (842 mg,
15.0 mmol.), CuI (57 mg, 0.3 mmol.), 1,10-phenanthrolene (108 mg, 0.6 mmol.), H2O (270
mg, 15.0 mmol.) was added into a vial containing anhydrous DMSO (5 mL). The suspension
o
was stirred for 12 h at 100 C. After cooling, the reaction mixture was diluted with 50 ml
EtOAc and filtered through a celite bed, bed washed with EtOAc (20 mL). Filtrate was
washed with water (2 × 25 mL), brine (2 × 25 mL), then dried over Na2SO4. Evaporation of
the solvent under reduced pressure provided the crude product, which was purified by column
chromatography (hexane= 100%) to afford the final product.
4.1.1. 2,5-Diphenylfuran (2a)12d
:

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Phenyl propiolic acid (439 mg, 3.0 mmol) afforded 2a (294 mg, 1.33 mmol, 89% yield) as an
off-white solid; mp: 65-67°C; 1H NMR (300 MHz, CDCl3) δ 7.74 (d, J = 7.2 Hz, 4H), 7.39 (t,
13
J = 7.6 Hz, 4H), 7.25 (t, J = 7.4 Hz, 2H), 6.72 (s, 2H); C NMR (75 MHz, CDCl3) δ 153.3,
130.7, 128.7, 127.3, 123.7, 107.2.
4.1.2. 2,5-Bis(o-tolyl)furan (2b)12c:
3-o-Tolylpropiolic acid (481 mg, 3.0 mmol) afforded 2b (276 mg, 1.22 mmol, 74%) as a
colorless oil; 1H NMR (300 MHz, CDCl3) δ 7.79 (d, J = 7.8 Hz, 2H), 7.42–7.05 (m, 6H), 6.66
(s, 2H), 2.56 (s, 6H); 13C NMR (75 MHz, CDCl3) δ 152.6, 134.4, 131.2, 130.0, 127.4, 126.8,
126.0, 110.5, 22.2.
4.1.3. 2,5-Bis(m-tolyl)furan (2c)12c:
3-m-Tolylpropiolic acid (481 mg, 3.0 mmol) afforded 2c (268 mg, 1.19 mmol, 72%) as a
1
colorless oil; H NMR (600 MHz, CDCl3) δ 7.55 (d, J = 12.4 Hz,4H), 7.33–7.24 (m, 2H),
13
7.07 (d, J = 7.5 Hz, 2H), 6.69 (s, 2H), 2.40 (s, 6H); C NMR (151 MHz, CDCl3) δ 153.3,
138.2, 130.7, 128.6, 128.1, 124.2, 120.9, 21.5.
4.1.4. 2,5-Bis(p-tolyl)furan (2d)12d:

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3-p-Tolylpropiolic acid (481 mg, 3.0) afforded 2d (317 mg, 1.25 mmol, 85%) as a off-white
1
solid; mp: 157-159 °C; H NMR (600 MHz, CDCl3) δ 7.62 (d, J = 8.2 Hz, 2H), 7.19 (d, J =
13
8.5 Hz, 2H), 6.65 (s, 1H), 2.36 (s, 6H); C NMR (151 MHz, CDCl3) δ 153.1, 137.0, 129.3,
128.1, 123.6, 106.4, 21.3.
4.1.5. 2,5-Bis(3,4-dimethylphenyl)furan (2e):
3-(3,4-Dimethylphenyl)propiolic acid (523 mg, 3.0 mmol) afforded 2e (336 mg, 1.22 mmol,
81%) as a colorless oil; 1H NMR (600 MHz, CDCl3) δ 7.50 (s, 2H), 7.47 (d, J = 9.7 Hz, 2H),
13
7.14 (d, J = 7.8 Hz, 2H), 6.63 (s, 2H), 2.28 (d, J = 23.5 Hz, 12H); C NMR (151 MHz,
CDCl3) δ 153.2, 136.8, 135.7, 129.9, 128.6, 124.8, 121.2, 106.3, 19.9, 19.6; HRMS (ESI)
calcd. for C20H21O [M+H]+ 277.1592 found 277.1592.
4.1.6. 2,5-Bis(4-ethylphenyl)furan (2f)12d:
3-(4-Ethylphenyl)propiolic acid (523 mg, 3.0 mmol) afforded 2f (365 mg, 1.32 mmol,
88%) as a off-white solid; mp: 145-147 °C; 1H NMR (300 MHz, CDCl3) δ 7.65 (d, J = 8.3 Hz,
4H), 7.22 (d, J = 8.4 Hz, 4H), 6.65 (s, 1H), 2.66 (q, J = 7.6 Hz, 4H), 1.25 (t, J = 7.6 Hz, 6H);
13C NMR (151 MHz, CDCl3) δ 153.2, 143.4, 128.4, 128.2, 123.7, 106.5, 28.7, 15.5.
4.1.7. 2,5-Bis(4-methoxyphenyl)furan (2g)12d:

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3-(4-Methoxyphenyl)propiolic acid (529 mg, 3.0 mmol) afforded 2g (319 mg, 1.13 mmol,
76%) as a off-white solid; mp: 188-190 °C; 1H NMR (600 MHz, CDCl3) δ 7.66 (d, J = 8.8 Hz,
13
2H), 6.94 (d, J = 8.8 Hz, 2H), 6.58 (s, 2H), 3.84 (s, 6H); C NMR (151 MHz, CDCl3) δ
158.8, 152.7, 124.9, 124.0, 114.1, 105.6, 55.3.
4.1.8. 2,5-Bis(2-methoxyphenyl)furan (2h)15:
3-(2-Methoxyphenyl)propiolic acid (529 mg, 3.0 mmol) afforded 2h (331 mg, 1.18 mmol,
79%) as a colorless oil; 1H NMR (600 MHz,CDCl3) δ 8.00 (d, J = 7.8 Hz, 1H), 7.22 (m, 2H),
13
7.11–7.01 (m, 2H), 6.95 (d, J = 8.3 Hz, 2H), 3.94 (s, 6H); C NMR (151 MHz, CDCl3) δ
155.4, 148.6, 127.7, 125.8, 120.7, 119.9, 112.4, 110.9, 55.3.
4.1.9. 2,5-Bis(4-chlorophenyl)furan (2i) 12d
:
3-(4-Chlorophenyl)propiolic acid (542 mg, 3.0 mmol) afforded 2i (278 mg, 0.96 mmol,
64% ) as a colorless oil; 1H NMR (600 MHz, CDCl3) δ 7.64 (d, J = 8.5 Hz, 1H), 7.36 (d, J =
13
8.5 Hz, 1H), 6.71 (s, 1H); C NMR (75 MHz, CDCl3) δ 152.5, 133.1, 129.0, 128.9, 124.9,
107.7.
4.1.10. 2,5-Bis(3-chlorophenyl)furan (2j)12d:

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3-(3-Chlorophenyl)propiolic acid (542 mg, 3.0 mmol) afforded 2j (291 mg, 1.01 mmol, 67%)
as a colorless oil; 1H NMR (600 MHz, CDCl3) δ 7.71 (s, 2H), 7.60 (d, J = 7.8 Hz, 2H), 7.33 (t,
13
J = 7.9 Hz, 2H), 7.27–7.21 (m, 2H), 6.76 (s, 2H); C NMR (151 MHz, CDCl3) δ 152.4,
134.8, 132.0, 130.0, 127.5, 123.7, 121.8, 108.3.
4.1.11. 2,5-Bis(2-fluorophenyl)furan (2k):
3-(2-Fluorophenyl)propiolic acid (492 mg, 3.0 mmol) afforded 2k (273 mg, 1.06 mmol, 71%)
as a off-white solid; mp: 127-129 °C; 1H NMR (300 MHz, CDCl3) δ 7.94 (m, 2H), 7.30–7.18
(m, 4H), 7.18–7.06 (m, 2H), 6.97 (d, J = 3.7 Hz, 2H); 13C NMR (75 MHz, CDCl3) δ 158.7 (d,
J = 251.1 Hz), 147.3, 128.41 (d, J = 8.4 Hz), 125.9 (d, J = 3.1 Hz), 124.3 (d, J = 3.5 Hz),
118.8 (d, J = 12.0 Hz), 115.9 (d, J = 21.4 Hz), 112.6 (d, J = 11.9 Hz). HRMS (ESI) calcd. for
C16H11F2O [M+H]+ 257.0778, found 257.0778.
4.1.12. 2,5-Bis(4-(trifluoromethyl)phenyl)furan (2l)12c:
3-(4-(Trifluoromethyl)phenyl)propiolic acid (642 mg, 3.0 mmol) afforded 2l (390 mg, 1.09
mmol, 73% ) as a off-white solid; mp: 140-142 °C; 1H NMR (300 MHz, CDCl3) δ 7.84 (d, J
13
= 8.8 Hz, 2H), 7.67 (d, J = 9.4 Hz, 2H), 6.88 (s, 1H); C NMR (75 MHz, CDCl3) δ 152.8,

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133.4, 129.3 (d, J = 32.6 Hz), 125.8 (q, J = 3.7 Hz), 123.9, 122.3, 109.3.
4.1.13. 2,5-Di(thiophen-2-yl)furan (2m)12c:
3-(Thiophen-2-yl)propiolic acid (457 mg, 3.0 mmol) afforded 2m (251 mg, 1.08 mmol,
72%) as a colorless oil; 1H NMR (300 MHz, CDCl3) δ 7.30 (d, J = 3.6 Hz, 2H), 7.22 (d, J =
13
5.0 Hz, 2H), 7.07–7.00 (m, 2H), 6.53 (s, 2H); C NMR (75 MHz, CDCl3) δ 148.5, 133.4,
127.7, 124.2, 122.6, 107.1.
4.1.14. 2,5-Di(naphthalen-1-yl)furan (2n)12c:
3-(Naphthalen-1-yl)propiolic acid (589 mg, 3.0 mmol) afforded the 2n (332 mg, 1.04 mmol,
69 % ) as a colorles oil; 1H NMR (300 MHz, CDCl3) δ 8.56 (d, J = 7.6 Hz, 2H), 7.93–7.77 (m,
6H), 7.52 (m, J = 7.4, 3.7 Hz, 6H), 6.92 (s, 2H); 13C NMR (75 MHz, CDCl3) δ 153.2, 134.0,
130.2, 128.6, 128.5, 126.6, 126.0, 125.9, 125.5, 125.4, 111.2.
4.2. General procedure for synthesis of 2,5-disubstituted thiophenes:
Phenyl propiolic acid (439 mg, 3.0 mmol), K2CO3 (830 mg, 6.0 mmol), CuI (57 mg, 0.3
mmol.), 1,10-phenanthrolene (108 mg, 0.6 mmol), was added into a vial containing
o
anhydrous DMSO (5 mL). The suspension was stirred for 12 h at 100 C. Reaction mixture
o
cooled to 25-27 C. KOH powder (170 mg, 3.0 mmol) and Na2S.9H2O (1.44 g, 6.0 mmol.)
o
were added and stirred for 6 h at 100 C. After cooling, the reaction mixture was filtered
through a celite bed and the bed washed with 20 ml of ethyl acetate. The filtrate diluted with

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EtOAc (50 mL) and washed with water (2 × 25 mL), brine (2 × 25 mL), then dried over
Na2SO4. Evaporation of the solvent under reduced pressure provided the crude product,
which was purified by column chromatography (hexane= 100%) to afford the final product.
4.2.1. 2,5-Diphenylthiophene (4a)12d:
Phenyl propiolic acid (438 mg, 3.0 mmol) afforded 4a (241 mg, 1.02 mmol, 68 % yield) as
colorless solid; mp: 152-155°C; 1H NMR (300 MHz, CDCl3) δ 7.63 (d, J = 7.2 Hz, 4H), 7.39
13
(t, J = 7.5 Hz, 4H), 7.29 (m, 2H); C NMR (75 MHz, CDCl3) δ 143.6, 134.3, 128.9, 127.5,
125.6, 124.0;
4.2.2. 2,5-Di-p-tolylthiophene (4d)12c:
3-p-Tolylpropiolic acid (481 mg, 3.0) afforded 4d (282 mg, 1.07 mmol, 71%) as an off-white
solid; mp: 161-164 °C; 1H NMR (300 MHz, CDCl3) δ 7.51 (d, J = 8.1 Hz, 4H), 7.22 (s, 2H),
13
7.18 (d, J = 7.9 Hz, 4H), 2.36 (s, 6H); C NMR (75 MHz, CDCl3) δ 143.2, 137.3, 131.6,
129.5, 125.5, 123.4, 21.2.
4.2.3. 2,5-Bis(3,4-dimethylphenyl)thiophene (4e):
3-(3,4-Dimethylphenyl)propiolic acid (523 mg, 3.0 mmol) afforded 4e (554 mg, 1.13 mmol,
75%) as a off-white solid; mp: 161-165 °C; 1H NMR (300 MHz, CDCl3) δ 7.40 (s, 2H), 7.36

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13
(d, J = 7.8 Hz, 2H), 7.21 (s, 2H), 7.13 (d, J = 7.8 Hz, 2H), 2.29 (d, J = 8.0 Hz, 12H); C
NMR (75 MHz, CDCl3) δ 137.0, 136.0, 132.0, 130.1, 126.8, 123.3, 123.0, 19.8, 19.5; HRMS
(ESI) calcd. for C20H21S [M+H]+ 293.1364, found 293.1364.
4.2.4. 2,5-Di(naphthalen-1-yl)thiophene (4n)16:
3-(Naphthalen-1-yl)propiolic acid (589 mg, 3.0 mmol) afforded the 4n (323 mg, 0.96 mmol,
1
64 % ) as a off-white solid; mp: 141-1435 °C; H NMR (300 MHz, CDCl3) δ 8.52–8.37 (m,
13
2H), 7.98–7.82 (m, 4H), 7.68 (m, 2H), 7.59–7.49 (m, 6H), 7.33 (s, 2H); C NMR (75 MHz,
CDCl3) δ 142.0, 133.9, 132.3, 131.7, 128.4, 128.1, 127.6, 126.5, 126.0, 125.8, 125.3.
4.2.5. 2,5-Bis(4-fluorophenyl)thiophene (4o)12c:
3-(4-Fluorophenyl)propiolic acid (492 mg, 3.0 mmol) afforded 4o (237 mg, 0.87 mmol, 58%)
as a off-white solid; Mp: 162-165 °C; 1H NMR (300 MHz, CDCl3) δ 7.65–7.50 (m, 2H), 7.19
(s, 2H), 7.07 (d, J = 8.6 Hz, 2H); 13C NMR (75 MHz, CDCl3) δ 162.3 (d, J = 247.4 Hz),
142.5, 130.5, 127.2 (d, J = 8.0 Hz), 124.0, 115.9 (d, J = 21.9 Hz).
Acknowledgements
This research was supported by Basic Science Research Program through the National
Research Foundation of Korea(NRF) funded by the Ministry of Science, ICT and future
Planning(NRF-2014R1A2A1A11050018). Spectra data were obtained from the Korea Basic

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Science Institute, Gwangju branch.
Supplementary data
Supplementary data related to this article can be found
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Supplementary Data
Copper-Catalyzed Direct Synthesis of Furan and Thiophene from the Decarboxylative
Coupling Reaction of Alkynyl Carboxylic Acid with H2O or Na2S..
Francis Mariaraj Irudayanathan, Gabriel Charles Edwin Raja, and Sunwoo Lee*
Department of Chemistry, Chonnam National University, Gwangju 500-757, Republic of Korea
Table of Contents
1H and 13C NMR Spectra
-S2-
S1

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2,5-Diphenylfuran (2a):
S2

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2,5-Diphenylfuran (2b):
S3

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2,5-Bis(m-tolyl)furan (2c):
S4

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2,5-Bis(p-tolyl)furan (2d):
S5

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2,5-Bis(3,4-dimethylphenyl)furan (2e):
S6