Palladium-Catalyzed Synthesis of (Z)-3-Arylthioacrylic Acids and Thiochromenones

Article abstract of DOI:10.1002/adsc.201201106

The three-component reaction of aryl halides, sodium sulfide pentahydrate (Na₂S×5 H₂O), and propiolic acid in the presence of 2.5% bis(triphenylphosphine)palladium chloride [Pd(PPh₃) ₂Cl₂], 5% 1,4-bis(diphenylphosphino)butane (dppb) and 2equivalents of 1,8-diazabicycloundec-7-ene (DBU) produces stereoselectively (Z)-3-arylthioacrylic acids in good yields. A study of the reaction pathway suggested that the C-S bond formation between aryl halides and Na ₂S×5 H₂O proceeded first, and the resulting intermediate reacted with propiolic acid to produce the desired product. In addition, when the resulting product was treated with acid, the respective thiochromenones were formed in good yields. Copyright

Full text of DOI:10.1002/adsc.201201106

FULL PAPERS
DOI: 10.1002/adsc.201201106
Palladium-Catalyzed Synthesis of (Z)-3-Arylthioacrylic Acids and
Thiochromenones
Thiruvengadam Palani,a Kyungho Park,a Kwang Ho Song,b,* and Sunwoo Leea,*
a
Department of Chemistry, Chonnam National University, Gwangju 500-757, Republic of Korea
Fax : (+82)-62-530-3389; e-mail: sunwoo@chonnam.ac.kr
Department of Chemical & Biological Engineering, Korea University, Seoul 136-713, Republic of Korea
b
E-mail: khsong@korea.ac.kr
Received: December 18, 2012; Revised: February 21, 2013; Published online: April 9, 2013
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201201106.
Abstract: The three-component reaction of aryl hal- halides and Na2S·5H2O proceeded first, and the re-
ides, sodium sulfide pentahydrate (Na2S·5H2O), and sulting intermediate reacted with propiolic acid to
propiolic acid in the presence of 2.5% bis(triphenyl- produce the desired product. In addition, when the
phosphine)palladium chloride [Pd
1,4-bis(diphenylphosphino)butane
ACHTUNGTRENNUNG
2 equivalents of 1,8-diazabicycloundec-7-ene (DBU)
produces stereoselectively (Z)-3-arylthioacrylic acids
in good yields. A study of the reaction pathway sug- Keywords: (Z)-alkenyl sulfides; cross-coupling; pal-
À
gested that the C S bond formation between aryl ladium; propiolic acid; thiochromenones
Introduction
provides anti-Markovnikov (Z)-alkenyl sulfides,
which was first reported by Truce.[11] Recently,
[12]
1-Alkenyl sulfides are important intermediates in the Cs2CO3 and (i-Pr)2NEt[13]-mediated hydrothiolation
synthesis of organic and polymeric materials due to has selectively produced the (Z) isomer. Although
their ease of transformation,[1] and are key structure these hydrothiolations have the potential to achieve
units in natural products and biologically active com- the stereoselective synthesis of (Z)-isomers, they have
pounds.[2] There have been numerous reported meth- had several drawbacks, including the need for radical
ods for the synthesis of 1-alkenyl sulfides, including scavengers or CO2 gas and their substrate scope was
the addition of thiols to alkynes,[3] Wittig olefination,[4] low. Furthermore, all these methods use thiols as
and the direct coupling reaction[5] of vinyl halides and starting materials. Thiols have drawbacks due to their
thiols. Among them, the hydrothiolations of alkynes strong and disagreeable odors, which can lead to envi-
with thiols are most frequently used, because other ronmental problems even though they are cheaper
methods require the preparation of starting materials, than aryl iodides. Thus, a simple, environmentally
harsh conditions, or show low stereoselectivity at the friendly, and efficient route with high stereoselectivity
double bond.
The hydrothiolation of alkynes with thiols is com- fides.
monly conducted through transformations with radi- Recently, we reported on transition metal-catalyzed
cals,[6] transition metal catalysts[7] and bases. Radical C S bond formation using sulfur surrogates,
is still required for the synthesis of (Z)-alkenyl sul-
[14]
À
and
hydrothiolation has afforded a mixture of anti-Mar- a variety of coupling reactions of propiolic acid.[15] As
kovnikov (E) and (Z) isomers. The transition metal- an expansion of these methodologies, we envisioned
catalyzed hydrothiolation has been carried out in that the combination of the two concepts would pro-
a syn-addition to provide the anti-Markovnikov (E)- vide an efficient method for the stereoselective syn-
alkenyl sulfide or Markovnikov product. However, thesis of 1-alkenyl sulfides. In addition, the resulting
the selective synthesis of (Z)-alkenyl sulfides using product, the (Z)-3-arylthioacrylic acid, should be
transition metal catalysts has rarely been reported. easily transformed to thiochromenones, which are
The employment of Rh,[8] Pd,[9] and Cu[10] has provid- very useful building blocks in bioactive and photo-
ed (Z) isomers as major products in the mixture of chemical compounds.[16]
(Z) and (E) isomers. Base-mediated hydrothiolation
1160
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2013, 355, 1160 – 1168

Palladium-Catalyzed Synthesis of (Z)-3-Arylthioacrylic Acids and Thiochromenones
Results and Discussion
First, the coupling reaction of iodobenzene,
Na2S·5H2O, and propiolic acid was conducted in the
presence of a palladium catalyst. After investigating
a variety of reaction parameters, we found the opti-
mized conditions for the synthesis of (Z)-2a, as shown
in Table 1.
When the reaction was carried out in the presence
of 2.5 mol% Pd
phosphiono)butane (dppb), and 1,8-diazabicyclo-
AHCTUNGTREGUN[NN 5.4.0]undec-7-ene (DBU) (2.0 equiv.) in DMSO at
ACHTUGNTERN(NUNG PPh3)2Cl2, 5.0 mol% 1,4-bis(diphenyl-
508C for 12 h, the desired product was obtained in
1
87% yield. The H NMR spectrum of the crude prod-
uct showed only the (Z) isomer, and no (E) isomer
was found in the reaction mixture. When a copper
catalyst was used instead of palladium catalyst, CuI
and CuCl, respectively, afforded the product in 25%
and 5% yields (entries 2 and 3). In the absence of Pd-
Scheme 1. Synthesis of alkenyl sulfides.
Herein, we report on the synthesis of (Z)-3-aryl-
ACHTUGNTNERN(UNG PPh3)2Cl2, dppb, or DBU, unsatisfactory yields of
ACHTUNGTRENNUNG
A
ACHTUNGTRENNUNG
Table 1. Optimization of the synthesis of (Z)-3-phenylthioacrylic acid.[a]
Entry
Change from the standard conditions
none
Yield [%]
1
87
2
3
4
5% CuI instead of 2.5% Pd
5% CuCl instead of 2.5% Pd
without 2.5% Pd(PPh3)2Cl2
G
25
5
32
E
G
5
6
7
8
without 5% dppb
without DBU
1108C without 2.5% PdACHTUNGTRENNUNG
30
41[b]
7[c]
25[d]
32[d]
46
DBU (4 equiv.) without 2.5% PdACHNUTGTRENNUNG
9
ACHTUNGTRENNUNG
10
11
12
13
14
15
16
17
18
19
20
T
N
ACHTUNGTRENNUNG
E
30
48
20
65
0
0
10% PPh3 instead of 5% dppb
10% dppe instead of 5% dppb
NaSH.nH2O instead of Na2S·5H2O
thiourea instead of Na2S·5H2O
sulfur in oil instead of Na2S·5H2O
K2CO3 (2 equiv.) instead of DBU (2 equiv.)
Cs2CO3 (2 equiv.) instead of DBU (2 equiv.)
258C (24 h) instead of 508C (12 h)
55[b]
45[b]
trace
40
358C (24 h) instead of 508CACTHNUTRGNE(UNG 12 h)
[a]
Reaction conditions: 1a (0.3 mmol), Na2S·5H2O (0.6 mmol), propiolic acid (0.3 mmol), Pd
(0.015 mmol), DBU (0. 6 mmol) were reacted in DMSO (2.0 mL) at 508C for 12 h.
The ratio of (Z)-2a/(E)-2a is 95/5.
The ratio of (Z)-2a/(E)-2a is 52/48.
The ratio of (Z)-2a/(E)-2a is 75/25.
ACHTUGNTRENUN(GN PPh3)2Cl2 (0.0075 mmol), dppb
[b]
[c]
[d]
Adv. Synth. Catal. 2013, 355, 1160 – 1168
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
1161

Thiruvengadam Palani et al.
FULL PAPERS
Table 2. Pd-catalyzed synthesis of (Z)-3-arylthioacrylic acids.[a]
Entry
Ar-X
Product
(Z)-2a
(Z)-2b
Yield [%]
Ratio[b] (Z)/(E)
only(Z)
1
2
1a
1b
85
77
98/2
3
1c
(Z)-2c
73
98/2
4
5
6
1d
1e
1f
(Z)-2d
(Z)-2e
(Z)-2f
66
77
72
98/2
97/3
96/4
7
1g
(Z)-2g
61
96/4
8
1h
1i
(Z)-2h
(Z)-2i
(Z)-2j
(Z)-2k
(Z)-2l
65
73
60
55
56
98/2
96/4
97/3
97/3
96/4
9
10
11
12
1j
1k
1l
13
14
15
1m
1n
1o
1p
(Z)-2m
(Z)-2n
(Z)-2o
(Z)-2p
75
71
52
47
94/6
94/6
only(Z)
only(Z)
16
17
18
1q
1r
1s
(Z)-2q
(Z)-2r
(Z)-2s
70
75
65
95/5
91/9
94/6
19
[a]
Reaction conditions: aryl halides (5.0 mmol), Na2S·5H2O (10.0 mmol), propiolic acid (6.0 mmol), Pd
(0.125 mmol), dppb (0.25 mmol), DBU (10.0 mmol) were reacted in DMSO (15.0 mL) at 508C for 12 h.
Determined by gas chromatography and 1H NMR.
ACHTUGNRTNE(NUNG PPh3)2Cl2
[b]
1162
asc.wiley-vch.de
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2013, 355, 1160 – 1168

Palladium-Catalyzed Synthesis of (Z)-3-Arylthioacrylic Acids and Thiochromenones
Table 3. Pd-catalyzed coupling reactions with b-substituted
propiolic acids.[a]
spectively (entries 10 and 11). Other ligands such as
PPh3 and 1,2-bis(dipehneylphosphino)ethane (dppe)
showed poor yields (entries 12 and 13). The replace-
ment of sulfur sources with KSAc, thiourea, and
sulfur did not afford the desired product (entries 14–
16). Inorganic base such as K2CO3 and K3PO4 showed
55% and 45% yields, respectively (entries 17 and 18).
Without DBU, the undesired (E)-isomer was formed
(entries 6, 17 and 18). Decreasing the temperature re-
sulted in low yields of product (entries 19 and 20).
To better evaluate the significance of this reaction
system, a range of aryl iodides was examined using
the preliminary optimized reaction conditions. The re-
sults are summarized in Table 2. As expected, iodo-
benzene produced the desired product in 85% isolat-
ed yield (entry 1). Alkyl-substituted aryl iodides
showed good yields with high stereoselectivity (en-
tries 2–6). ortho-, meta-, and para-iodoanisoles afford-
ed the corresponding arylthioacrylic acids in 61%,
65%, and 73% yields, respectively (entries 7–9). Aryl
Entry
1
R
Product
Yield [%]
1
2
3
4
5
1a
1k
1a
1a
1a
Me
Me
Et
Pent
Ph
(Z)-2a-Me
(Z)-2k-Me
(Z)-2a-Et
–
50
35
45
–
–
–
[a]
Reaction conditions: aryl halides (5.0 mmol), Na2S·5H2O
(10.0 mmol), b-substituted propiolic acid (6.0 mmol),
PdACTHUNTGRNENUG(PPh3)2Cl2 (0.125 mmol), dppb (0.25 mmol), DBU
(10.0 mmol) were reacted in DMSO (15.0 mL) at 508C
for 12 h.
iodides bearing a halide group such as fluoride, chlo- Most of the (Z)-arylthioacrylic acids which were
ride, and bromide exhibited moderate yields (en- formed from aryl halides afforded the desired thio-
tries 10–12). 1-Naphthyl iodide showed 75% yield chromenones in good yields. As shown in Table 4,
(entry 13). 4-Trifluoromethylphenyl iodide provided phenyl iodide (1a) and aryl iodides bearing alkyl or
the desired product in 71% yield (entry 14). 4’-Iodoa- halo groups such as 1b–f and 1j, k afforded the de-
cetophenone and 4-iodobenzonitrile also produced sired thiochromenones (entries 1–9). 4-Trifluorome-
the desired products in 52% and 47% yields, respec- thyliodobenzene showed 73% yield (entry 10). How-
tively (entries 15 and 16). In addition, when aryl bro- ever, iodoanisoles (1g–i) and 1-iodonaphthalene (1m)
mides were employed instead of aryl iodides and the did not produce the corresponding thiochromenones
coupling reactions were conducted at 708C, they af- (not shown in Table 4). In addition, the reaction of 1-
forded the desired products in good yields (en- chloro-4-iodobenzene and butynoic acid afforded the
tries 15–17). However, chlorobenzene produced a mix- desired thiochromenone 3k-Me in 32% (entry 11).
ture of (Z)- and (E)-3-(phneylthio)acrylic acid in
To investigate the reaction pathway, the coupling
trace amounts (not shown in Table 2). As shown in reaction of phenyl iodide and Na2S·5H2O was con-
Table 2, we found that the ratio of the formation of ducted in the absence of propiolic acid. As shown in
(Z)- and (E)-isomers was dependent on the aryl io- Scheme 2, the thiophenol was formed with 89% yield
dides. They produced 2–10% yields of (E)-isomers.
[Eq. (1)]. However, the desired product was not
We applied these optimized conditions for the cou- formed, when propiolic acid and Na2S·5H2O was first
pling of b-substituted propiolic acids such as 2-buty- reacted in the presence of palladium and base fol-
noic acid, 2-pentynoic acid, 2-octynoic acid and phe- lowed by the addition of phenyl iodide [Eq. (2)].
À
nylpropiolic acid. The results are summarized in These results suggested the C S bond formation of
Table 3. The coupling reactions of 2-butynoic acid aryl iodide and Na2S first occurred, and the resulting
with iodobenzene and 1-chloro-4-iodobenzene pro- intermediate then reacted with propiolic acid.
duced the corresponding products in 50% and 35%
Next, to study the high stereoselectivity of (Z)-
yields, respectively (entries 1 and 2). 2-Pentynoic acid isomer, a variety of thio compounds, which are ex-
showed 45% yield in the coupling with iodobenzene pected products in the reaction mixture of the previ-
À
(entry 3). However, more sterically demanding sub- ous C S bond formations, was employed as a coupling
strates such as 2-octynoic acid and phenylpropiolic partner in the reaction with propiolic acid (Table 5).
acid did not produce the coupled products (entries 4
and 5).
When thiophenol was employed as a coupling part-
ner, it did not give the desired product in the absence
The selective formation of the (Z) isomer allowed of catalyst and base (entry 1). The addition of
us to develop the one-pot synthesis of thiochrome- Na2S·5H2O gave the desired product in 30% yield
nones. The reaction of aryl halides, sodium sulfide, with the ratio of 10/1 (entry 2). The reaction with pal-
and propiolic acid was first carried out in the presence ladium catalyst and DBU showed 35% yield of prod-
of palladium catalyst and base at 508C for 12 h, and uct, but the (E)-isomer was the major product
then the resulting reaction mixture was heated with (entry 3). When Na2S·5H2O was added under the con-
the addition of conc. H2SO4 (10 mol%) for 1.5 h. ditions of entry 2, the (Z)-product was formed with
Adv. Synth. Catal. 2013, 355, 1160 – 1168
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
1163

Thiruvengadam Palani et al.
FULL PAPERS
Table 4. Synthesis of thiochromenones.[a]
Table 5. Synthesis of 3-phenylthioacrylic acid from thio com-
pounds.[a]
Entry PhS- Additives[b] Na2S·5H2O Yield
Ratio (Z)/
(E)
Z
(%)
1
2
3
4
5
6
7
8
4a
4a
4a
4a
4b
4b
4b
4b
4c
4c
4c
4c
w/o[c]
w/o
w[d]
w
w/o
w/o
w
w/o
w
w/o
w
w/o
w
w/o
w
w/o
w
w/o
w
trace
30
35
84
32
35
70
76
28
35
60
65
–
10/1
1/1.4
20/1
3/1
20/1
3.7/1
50/1
2/1
w
9
w/o
w/o
w
10
11
12
5/1
2.9/1
11.1/1
w
[a]
Reaction conditions: 4 (3.0 mmol) and propiolic acid
(3.0 mmol) were reacted in DMSO at 508C for 12 h.
PdACTHUNTGRNENUG(PPh3)2Cl2 (0.075 mmol), dppb (0.15 mmol), DBU
[b]
(6.0 mmol)
w/o: in the absence of reagents
w: in the presence of reagents.
[c]
[d]
catalyst was added to the conditions of absence and
presence of Na2S·5H2O, their yields were increased.
However, the stereoselectivity in the presence of
[a]
Reaction conditions: i) aryl halides (3.0 mmol),
Na2S·5H2O (6.0 mmol), propiolic acid (3.0 mmol),
PdACHTUNGTRENNUNG(PPh3)2Cl2 (0.075 mmol), dppb (0.15 mmol), DBU Na2S·5H2O is higher than in the absence (entries 7
(6.0 mmol) were reacted in DMSO (15.0 mL) at 508C for
12 h; ii) H2SO4 (0.3 mmol) was added and heated at
1008C for 1.5 h.
and 8). These trends in the yield and the stereoselec-
tivity were similar in the reaction of diphenyl disul-
fide. The reaction in the absence of palladium afford-
ed the desired product with low yields (entries 9 and
10). The reaction with Na2S·5H2O showed higher ste-
reoselectivity (entries 10 and 12). And the reaction
with palladium and Na2S·5H2O showed good yield
and selectivity (entry 12). It was found that all reac-
tions without Na2S·5H2O showed low stereoselectivity
(entries 3, 5, 7, 9 and 11). From these results, we
found that Na2S·5H2O is not only a sulfur source, but
also a key reagent for showing high stereoselectivity.
In addition, palladium is also important reagent to get
high yield.
Based on these results, we suggest the reaction
mechanism shown in Scheme 3. Aryl halide reacted
with palladium(0) to produce the oxidative adduct.
Scheme 2. Studies on the reaction pathways.
the ratio of 20/1 (entry 4). Next, sodium thiophenox- The resulting palladium complex reacted with
ide was reacted in the absence or presence of palladi- Na2S·5H2O to form sodium thiophenoxide through
um catalyst. In the absence of palladium, the yields of transmetallation and reductive elimination steps. The
product were low, however, the reaction without resulting intermediate, sodium thiophenoxide, reacted
Na2S·5H2O showed lower selectivity than that with with propiolic acid salt A, which is activated by palla-
Na2S·5H2O (entries 5 and 6). When the palladium dium, and produced the desired (Z)-arylthioacrylic
1164
asc.wiley-vch.de
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2013, 355, 1160 – 1168

Palladium-Catalyzed Synthesis of (Z)-3-Arylthioacrylic Acids and Thiochromenones
(Z)-3-(Phenylthio)acrylic acid (2a):[18] Iodobenzene
(1.02 g, 5.0 mmol), Na2S·5H2O (1.69 g, 10.0 mmol), DBU
(1.52 g, 10.0 mmol) and propiolic acid (420 mg, 6.0 mmol)
gave 2a; yield: 766 mg (4.25 mmol, 85%). 1H NMR
(300 MHz, DMSO-d6): d=12.42 (s, 1H), 7.54–7.48 (m, 3H),
7.46–7.25 (m, 3H), 5.93 (d, J=10.0 Hz, 1H); 13C NMR
(75 MHz, DMSO-d6): d=167.1, 148.3, 135.7, 130.0, 129.5,
128.0, 114.3.
(Z)-3-(p-Tolylthio)acrylic acid (2b):[19] 4-Iodobenzene
(1.09 g, 5.0 mmol), Na2S·5H2O (1.69 g, 10.0 mmol), DBU
(1.52 g, 10.0 mmol) and propiolic acid (420 mg, 6.0 mmol)
gave 2b; yield: 748 mg (3.85 mmol, 77%). 1H NMR
(300 MHz, CDCl3): d=7.44-7.32 (m, 3H), 7.19 (dd, J=8.4,
0.6 Hz, 2H), 5.92 (d, J=10.2 Hz, 1H), 2.36 (s, 3H);
13C NMR (75 MHz, CDCl3): d=171.6, 153.8, 138.7, 132.4,
131.3, 130.1, 112.2, 21.1; HR-MS (ESI): m/z=194.0482,
calcd. for C10H11O2S [M+H]+: 195.0480.
(Z)-3-(m-Tolylthio)acrylic acid (2c): 3-Iodobenzene
(1.09 g, 5.0 mmol), Na2S·5H2O (1.69 g, 10.0 mmol), DBU
(1.52 g, 10.0 mmol) and propiolic acid (420 mg, 6.0 mmol)
gave 2 ; yield: 709 mg (3.65 mmol, 73%). 1H NMR
(300 MHz, CDCl3): d=7.43 (d, J=10.2 Hz, 1H), 7.31-7.23
(m, 3H), 7.17-7.14 (m, 1H), 5.93 (d, J=10.2 Hz, 1H), 2.37
(s, 3H); 13C NMR (75 MHz, CDCl3): d=171.8, 153.2, 139.4,
135.5, 131.7, 129.2, 128.1, 112.4, 21.3; HR-MS (ESI): m/z=
194.0482, calcd. for C10H11O2S [M+H]+: 195.0480.
Scheme 3. Proposed mechanism.
acids (path a). Attempts to isolate palladium inter-
mediate A by using a metal salt of the propiolic acid
failed. When PdACHTUNGTRENNUNG(OAc)2 and in-situ generated sodium
propiolate were reacted, we found that an unidenti-
fied black precipitate was formed.[17] However, we did
not rule out the path b from the formation of diaryl
disulfide in the reaction due to the result of entry 12
in Table 5.
(Z)-3-(3,4-Dimethylphenylthio)acrylic acid (2d): 4-Iodo-
1,2-dimethylbenzene (1.16 g, 5.0 mmol), Na2S·5H2O (1.68 g,
10.0 mmol), DBU (1.52 g, 10.0 mmol) and propiolic acid
(420 mg, 6.0 mmol) gave 2d; yield: 687 mg (3.30 mmol,
Conclusions
In summary, we have developed a stereoselective syn-
thesis of (Z)-arylthioacrylic acids from the three-com-
ponent reaction of aryl halides, Na2S·5H2O, and pro-
1
66%). H NMR (300 MHz, CDCl3): d=7.40 (d, J=10.2 Hz,
1H), 7.21 (m, 3H), 5.90 (d, J=10.2 Hz, 1H), 2.27 (s, 6H);
13C NMR (75 MHz, CDCl3): d=171.8, 154.1, 138.0, 137.4,
132.5, 132.4, 130.6, 128.8, 112.0, 19.7, 19.5; HR-MS (ESI):
m/z=208.0632, calcd. for C11H13O2S [M+H]+: 209.0636.
(Z)-3-(4-Ethylphenylthio)acrylic acid (2e): 1-Ethyl-4-iodo-
benzene (1.16 g, 5.0 mmol), Na2S·5H2O (1.68 g, 10.0 mmol),
DBU (1.52 g, 10.0 mmol) and propiolic acid (420 mg,
6.0 mmol) gave 2e; yield: 802 mg (3.85 mmol, 77%).
1H NMR (300 MHz, CDCl3): d=7.42-7.38 (m, 3H), 7.23 (m,
2H), 5.92 (d, J=10.2 Hz, 1H), 2.66 (q, J=7.6 Hz, 2H), 1.24
(t, J=7.6 Hz, 3H); 13C NMR (75 MHz, CDCl3): d=171.8,
153.9, 145.0, 132.5, 131.4, 129.0, 112.2, 28.5, 15.4; HR-MS
(ESI): m/z=208.0638, calcd. for C11H13O2S [M+H]+:
209.0636.
À
piolic acid. We suggested that the C S bond forma-
tion of aryl iodide and Na2S·5H2O occurred first, and
then reacted with propiolic acid. We found that
Na2S·5H2O has key role in the highly stereoselective
formation of (Z)-isomer. In addition, the resulting ar-
ylthioacryl acids were easily transformed into thio-
chromenones. This method is free of toxic and smelly
thiols, and this report is the first on the one-pot direct
synthesis of thiochromenones from aryl halides.
Experimental Section
(Z)-3-(4-tert-Butylphenylthio)acrylic acid (2f): 1-tert-
Butyl-4-iodobenzene (1.30 g, 5.0 mmol), Na2S·5H2O (1.68 g,
10.0 mmol), DBU (1.52 g, 10.0 mmol) and propiolic acid
(420 mg, 6.0 mmol) gave 2f; yield: 851 mg (3.60 mmol,
72%). 1H NMR (300 MHz, CDCl3): d=7.46-7.37 (m, 5H),
5.92 (d, J=10.2 Hz, 1H), 1.32 (s, 9H); 13C NMR (75 MHz,
CDCl3): d=171.6, 153.8, 151.9, 132.4, 131.1, 126.5, 112.2,
34.7, 31.2; HR-MS (ESI): m/z=236.0941, calcd. for
C13H17O2S [M+H]+: 237.0949.
(Z)-3-(2-Methoxyphenylthio)acrylic acid (2g): 2-Iodoani-
sole (1.170 g, 5.0 mmol), Na2S·5H2O (1.68 g, 10.0 mmol),
DBU (2.28 g, 15.0 mmol) and propiolic acid (420 mg,
6.0 mmol) gave 2g; yield: 652 mg (3.10 mmol, 61%).
1H NMR (300 MHz, CDCl3): d=7.46 (dd, J=7.6, 1.6 Hz,
1H), 7.39-7.28 (m, 2H), 7.03-6.89 (m, 2H), 5.93 (d, J=
10.2 Hz, 1H), 3.89 (s, 3H); 13C NMR (75 MHz, CDCl3): d=
172.0, 158.2, 153.6, 133.4, 130.4, 123.1, 121.1, 112.2, 111.4,
General Procedure for the Synthesis (Z)-3-
(Phenylthio)acrylic Acids
In
a
50-mL flask were charged aryl halide (1.02 g,
(PPh3)2Cl2
5.0 mmol), Na2S·5H2O (1.69 g, 10.0 mmol), Pd
AHCTUNGTRENNUNG
(88 mg, 0.125 mmol), dppb (107 mg, 0.25 mmol), and the
mixture was stirred with DMSO for 5 min. And then DBU
(1.37 g, 10.0 mmol) and propiolic acid (918 mg, 6.0 mmol) or
b-substituted propiolic acid (6.0 mmol) were reacted at
508C for 12 h. After cooling, the mixture was poured into
water acidified with dil.HCl then extracted with dichlorome-
thane (50.0 mL) and washed with water (3ꢁ25.0 mL), brine
(3ꢁ25.0 mL), and then dried over MgSO4 and passed
through a celite pad. Evaporation of the solvent under re-
duced pressure provided the crude product, which was puri-
fied by column chromatography (hexane:EtOAc=4:1) to
afford the final product.
Adv. Synth. Catal. 2013, 355, 1160 – 1168
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
1165

Thiruvengadam Palani et al.
FULL PAPERS
55.8; HR-MS (ESI): m/z=210.0429, calcd. for C10H11O3S
[M+H]+: 211.0429.
(Z)-3-[4-(Trifluoromethyl)phenylthio]acrylic acid (2n): 1-
Iodo-4-(trifluoromethyl)benzene
(1.36 g,
5.0 mmol),
Na2S·5H2O (1.68 g, 10.0 mmol), DBU (2.28 g, 15.0 mmol)
(Z)-3-(3-Methoxyphenylthio)acrylic acid (2h): 3-Iodoani-
sole (1.170 g, 5.0 mmol), Na2S·5H2O (1.68 g, 10.0 mmol),
DBU (2.28 g, 15.0 mmol) and propiolic acid (420 mg,
6.0 mmol) gave 2h; yield: 683 mg (3.25 mmol, 65%).
1H NMR (300 MHz, CDCl3): d=7.45 (d, J=10.2 Hz, 1H),
7.33 (m, 1H), 7.10 (m, 2H), 6.89 (m, 1H), 5.95 (d, J=
10.1 Hz, 1H), 3.82 (s, 3H); 13C NMR (75 MHz, CDCl3) d
171.7, 160.0, 152.7, 136.9, 130.3, 123.2, 116.4, 114.3, 112.5,
55.4; HR-MS (ESI): m/z=210.0429, calcd. for C10H11O3S
[M+H]+: 211.0429.
(Z)-3-(4-Methoxyphenylthio)acrylic acid (2i): 4-Iodoani-
sole (1.170 g, 5.0 mmol), Na2S·5H2O (1.68 g, 10.0 mmol),
DBU (2.28 g, 15.0 mmol) and propiolic acid (420 mg,
6.0 mmol) gave 2i; yield: 765 mg (3.64 mmol, 73%).
1H NMR (300 MHz, CDCl3): d=7.43 (d, J=8.9 Hz, 2H),
7.33 (d, J=10.1 Hz, 1H), 6.91 (d, J=8.9 Hz, 2H), 5.89 (d,
J=10.1 Hz, 1H), 3.83 (s, 3H); 13C NMR (75 MHz, CDCl3) d
171.6, 160.1, 154.9, 133.5, 126.6, 115.0, 111.8, 55.4; HR-MS
(ESI): m/z=210.0429, calcd. for C10H11O3S [M+H]+:
211.0429.
and propiolic acid (420 mg, 6.0 mmol) gave 2n; yield:
1
876 mg (3.53 mmol, 71%). H NMR (300 MHz, CDCl3): d=
7.63 (m, 4H), 7.41 (d, J=10.1 Hz, 1H), 6.05 (d, J=10.1 Hz,
1H); 13C NMR (75 MHz, CDCl3): d=171.0, 150.3, 140.5,
130.7, 126.3 (q, JCÀF =3.8 Hz), 113.8; HR-MS (ESI): m/z=
248.0197, calcd. for C10H8F3O2S [M+H]+: 249.0197.
(Z)-3-(4-Acetylphenylthio)acrylic acid (2o): 4’-Iodoaceto-
phenone (1.23 g, 5.0 mmol), Na2S·5H2O (1.68 g, 10.0 mmol),
DBU (1.52 g, 10.0 mmol) and propiolic acid (420 mg,
6.0 mmol) gave 2o as a white solid after chromatography;
yield: 577 mg (2.60 mmol, 52%). 1H NMR (300 MHz,
DMSO-d6): d=12.57 (s, 1H), 7.97 (d, J=8.7 Hz, 2H), 7.66
(dd, J=9.3, 2.9 Hz, 3H), 6.03 (d, J=9.9 Hz, 1H), 2.58 (s,
3H); 13C NMR (75 MHz, DMSO): d=197.2, 167.1, 145.3,
141.7, 135.5, 129.1, 128.7, 115.6, 26.8; HR-MS (ESI): m/z=
222.2603, calcd. for C11H11O3S [M+H]+: 223.2623.
(Z)-3-(4-Cyanophenylthio)acrylic acid (2p): 4-iodobenzo-
nitrile (1.15 g, 5.0 mmol), Na2S·5H2O (1.68 g, 10.0 mmol),
DBU (1.52 g, 10.0 mmol) and propiolic acid (420 mg,
6.0 mmol) gave 2p as a white solid after chromatography;
yield: 482 mg (2.35 mmol, 47%). 1H NMR (300 MHz,
DMSO-d6): d=12.62 (s, 1H), 7.90–7.83 (m, 2H), 7.75–7.66
(m, 3H), 6.05 (d, J=9.9 Hz, 1H); 13C NMR (75 MHz,
DMSO-d6): d=167.0, 144.5, 142.3, 133.0, 129.3, 118.5, 116.0,
109.8; HR-MS (ESI): m/z=206.0276, calcd. for C10H8NO2S
[M+H]+: 206.0276.
(Z)-3-(4-Fluorophenylthio)acrylic acid (2j): 1-Fluoro-4-io-
dobenzene (1.11 g, 5.0 mmol), Na2S·5H2O (1.68 g,
10.0 mmol), DBU (3.81 g, 25.0 mmol) and propiolic acid
(420 mg, 6.0 mmol) gave 2j; yield: 595 mg (3.00 mmol,
1
60%). H NMR (300 MHz, CDCl3): d=7.48 (m, 2H), 7.32
(d, J=10.1 Hz, 1H), 7.08 (m, 2H), 5.94 (d, J=10.1 Hz, 1H);
13C NMR (75 MHz, CDCl3): d=171.6, 163.0 (d, JC,F
=
(Z)-3-(Biphenyl-4-ylthio)acrylic acid (2q): 4-Bromobi-
phenyl (1.17 g, 5.0 mmol), Na2S·5H2O (1.68 g, 10.0 mmol),
DBU (3.82 g, 25.0 mmol) and propiolic acid (420 mg,
6.0 mmol) gave 2q; yield: 897 mg (3.50 mmol, 70%).
1H NMR (300 MHz, CDCl3): d=7.63–7.55 (m, 6H), 7.49–
7.38 (m, 4H), 5.98 (d, J=10.1 Hz, 1H); 13C NMR (75 MHz,
CDCl3): d=171.1, 152.9, 141.5, 139.9, 134.7, 131.5, 128.9,
128.1, 127.8, 127.1, 112.5; HR-MS (ESI): m/z=256.0636,
calcd. for C15H13O2S [M+H]+: 257.0636.
(Z)-3-(Naphthalen-2-ylthio)acrylic acid (2r): 2-Bromo-
naphthalene (1.04 g, 5.0 mmol), Na2S·5H2O (1.68 g,
10.0 mmol), DBU (3.82 g, 25.0 mmol) and propiolic acid
(420 mg, 6.0 mmol) gave 2r; yield: 866 mg (3.76 mmol,
75%). 1H NMR (300 MHz, CDCl3): d=7.99 (d, J=1.7 Hz,
1H), 7.88–7.80 (m, 3H), 7.57-7.51 (m, 4H), 6.00 (d, J=
10.1 Hz, 1H); 13C NMR (75 MHz, CDCl3): d=171.6, 152.9,
133.5, 132.9, 132.7, 130.4, 129.3, 128.1, 127.8, 127.6, 127.0,
126.9, 112.8; HR-MS (ESI): m/z=230.0485, calcd. for
C13H11O2S [M+H]+: 231.0480.
248.2 Hz), 153.3, 133.7, 131.0, 116.6 (JC,F =21.7 Hz), 112.6;
HR-MS (ESI): m/z=199.0229, calcd. for C9H8FO2S [M+
H]+: 199.0229.
(Z)-3-(4-Chlorophenylthio)acrylic acid (2k): 1-Chloro-4-
iodobenzene (1.19 g, 5.0 mmol), Na2S·5H2O (1.68 g,
10.0 mmol), DBU (3.80 g, 25.0 mmol) and propiolic acid
(420 mg, 6.0 mmol) gave 2k; yield: 590 mg (2.75 mmol,
55%). 1H NMR (300 MHz, CDCl3): d=7.44-7.41 (m, 2H),
7.38-7.32 (m, 3H), 5.97 (d, J=10.1 Hz, 1H); 13C NMR
(75 MHz, CDCl3): d=171.1, 152.1, 134.8, 134.3, 132.5, 129.6,
113.0; HR-MS (ESI): m/z=213.9934, calcd. for C9H8ClO2S
[M+H]+: 213.9934.
(Z)-3-(4-Bromophenylthio)acrylic acid (2l): 1-Bromo-4-io-
dobenzene (1.42 g, 5.0 mmol), Na2S·5
H2O (1.68 g, 10.0 mmol), DBU (3.82 g, 25.0 mmol) and pro-
piolic acid (420 mg, 6.0 mmol) gave 2l; yield: 723 mg
1
(2.79 mmol, 56%). H NMR (300 MHz, CDCl3): d=7.52 (d,
J=8.6 Hz, 2H), 7.35 (dd, J=9.3, 6.0 Hz, 3H), 5.98 (d, J=
10.1 Hz, 1H); 13C NMR (75 MHz, CDCl3): d=171.0, 151.9,
134.9, 132.7, 132.6, 122.9, 113.0; HR-MS (ESI): m/z=
258.9428, calcd. for C9H8BrO2S [M+H]+: 258.9428.
(Z)-3-(Benzo[d]
ACHTUNGTRENUN[NG 1,3]dioxol-5-ylthio)acrylic acid (2s): 5-
Bromobenzo[d][1,3]dioxole (1.01 g, 5.0 mmol), Na2S·5H2O
AHCTUNGTRENNUNG
(1.68 g, 10.0 mmol), DBU (3.82 g, 25.0 mmol) and propiolic
(Z)-3-(Naphthalen-1-ylthio)acrylic acid (2m): 1-Iodonaph-
thalene (1.27 g, 5.0 mmol), Na2S·5H2O (1.68 g, 10.0 mmol),
DBU (2.28 g, 15.0 mmol) and propiolic acid (420 mg,
6.0 mmol) gave 2m; yield: 864 mg (3.75 mmol, 75%).
1H NMR (300 MHz, CDCl3). d=8.36 (d, J=8.1 Hz, 1H),
7.91 (dd, J=8.4, 1.2 Hz, 2H), 7.80 (dd, J=7.2, 1.2 Hz, 1H),
7.59 (m, 2H), 7.48 (dd, J=8.2, 6.0 Hz, 1H), 7.29 (d, J=
10.1 Hz, 1H), 5.98 (d, J=10.1 Hz, 1H); 13C NMR (75 MHz,
CDCl3). d=171.5, 154.1, 134.2, 133.3, 132.6, 132.3, 130.1,
128.7, 127.3, 126.6, 125.6, 125.5, 112.6; HR-MS (ESI): m/z=
230.0485, calcd. for C13H11O2S [M+H]+: 231.0480.
acid (420 mg, 6.0 mmol) gave 2s; yield: 729 mg (3.25 mmol,
65%). H NMR (300 MHz, CDCl3): d=7.33 (d, J=10.1 Hz,
1
1H), 7.04-6.94 (m, 2H), 6.80 (m, 1H), 6.01 (s, 2H), 5.90 (d,
J=10.1 Hz, 1H); 13C NMR (75 MHz, CDCl3): d=170.8,
154.4, 148.4, 148.3, 127.9, 126.1, 112.3, 111.8, 109.0, 101.6;
HR-MS (ESI): m/z=224.0222, calcd. for C10H9O4S [M+
H]+: 225.0222.
(Z)-3-(Phenylthio)but-2-enoic acid (2a-Me): Iodobenzene
(1.02 g, 5.0 mmol), Na2S·5H2O (1.69 g, 10.0 mmol), DBU
(1.52 g, 10.0 mmol) and 2-butynoic acid (504 mg, 6.0 mmol)
gave 2a-Me as a white solid after chromatography; yield:
1166
asc.wiley-vch.de
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2013, 355, 1160 – 1168

Palladium-Catalyzed Synthesis of (Z)-3-Arylthioacrylic Acids and Thiochromenones
1
482 mg (2.48 mmol, 50%). H NMR (300 MHz, CDCl3): d=
7.54-7.37 (m, 5H), 5.19 (q, J=1.0 Hz, 1H), 2.42 (d, J=
1.0 Hz, 3H); 13C NMR (75 MHz, CDCl3): d=170.6, 163.5,
135.5, 130.1, 129.8, 129.2, 109.8, 20.4; HR-MS (ESI): m/z=
195.0480, calcd. for C10H11O2S [M+H]+: 195.0480.
29.7; HR-MS (ESI): m/z=176.0374, calcd. for C10H9OS
[M+H]+: 177.0374.
6-Methyl-4H-thiochromen-4-one
(3c):
4-Iodotoluene
(654 mg, 3.0 mmol) gave 3c; yield: 363 mg (2.06 mmol,
1
69%). H NMR (300 MHz, CDCl3): d=8.36 (m, 1H), 7.82
(Z)-3-(4-Chlorophenylthio)but-2-enoic acid (2k-Me): 1-
Chloro-4-iodobenzene (1.19 g, 5.0 mmol), Na2S·5H2O
(1.68 g, 10.0 mmol), DBU (3.80 g, 25.0 mmol) and 2-butyno-
ic acid (503 mg, 6.0 mmol) gave 2k-Me as a white solid after
(d, J=10.4 Hz, 1H), 7.51 (d, J=8.2 Hz, 1H), 7.43 (m, 1H),
7.00 (d, J=10.4 Hz, 1H), 2.48 (s, 3H); 13C NMR (75 MHz,
CDCl3): d=179.7, 138.2, 137.7, 134.5, 132.8, 132.1, 128.3,
126.5, 125.6, 21.3; HR-MS (ESI): m/z=176.0374, calcd. for
C10H9OS [M+H]+: 177.0374.
1
chromatography; yield: 400 mg (1.75 mmol, 35%). H NMR
(300 MHz, CDCl3): d=7.42 (s, 4H), 5.18 (d, J=1.1 Hz, 1H),
2.42 (d, J=1.1 Hz, 3H); 13C NMR (75 MHz, CDCl3): d=
169.1, 162.9, 157.4, 136.8, 136.7, 130.2, 127.6, 109.8, 20.3;
HR-MS (ESI): m/z=229.0092, calcd. for C10H10ClO2S [M+
H]+: 229.0090.
6,7-Dimethyl-4H-thiochromen-4-one (3d): 4-Iodo-1,2-di-
methylbenzene (696 mg, 3.0 mmol) gave 3d; yield: 376 mg
(1.98 mmol, 66%). H NMR (300 MHz, CDCl3): d=8.31 (s,
1H), 7.78 (d, J=10.4 Hz, 1H), 7.38 (s, 1H), 6.98 (d, J=
10.4 Hz, 1H), 2.39 (s, 3H), 2.38 (s, 3H); 13C NMR (75 MHz,
CDCl3): d=179.8, 141.8, 137.5, 137.4, 135.0, 130.4, 128.7,
126.9, 125.7, 20.0, 19.7; HR-MS (ESI): m/z=190.0531, calcd.
for C11H11OS [M+H]+: 191.0531.
1
(Z)-3-(Phenylthio)pent-2-enoic acid (2a-Et): Iodobenzene
(1.02 g, 5.0 mmol), Na2S·5H2O (1.69 g, 10.0 mmol), DBU
(1.52 g, 10.0 mmol) and 2-pentynoic acid (589 mg, 6.0 mmol)
gave 2a-Et as a white solid after chromatography, yield:
6-Ethyl-4H-thiochromen-4-one (3e): 4-Ethyl-4-iodoben-
zene (696 mg, 3.0 mmol) gave 3e; yield: 445 mg (2.34 mmol,
1
470 mg (2.26 mmol, 45%). H NMR (300 MHz, CDCl3): d=
1
7.60–7.50 (m, 2H), 7.43–7.35 (m, 3H), 5.88 (s, 1H), 2.13 (qd,
J=7.3, 1.0 Hz, 2H), 0.99 (t, J=7.3 Hz, 3H); 13C NMR
(75 MHz, CDCl3): d=170.9, 166.9, 136.0, 130.2, 129.5, 129.1,
109.7, 30.3, 13.5; HR-MS (ESI): m/z=209.0636, calcd. for
C11H13O2S [M+H]+: 209.0636.
78%). H NMR (300 MHz, CDCl3): d=8.39 (m, 1H), 7.82
(d, J=10.4 Hz, 1H), 7.53–7.48 (m, 2H), 7.01 (d, J=10.4 Hz,
1H), 2.79 (q, J=7.6 Hz, 2H), 1.30 (t, J=7.6 Hz, 3H);
13C NMR (75 MHz, CDCl3): d=179.8, 144.5, 137.7, 134.7,
132.2, 131.8, 127.2, 126.6, 125.6, 28.7, 15.4; HR-MS (ESI):
m/z=190.0531, calcd. for C11H11OS [M+H]+: 191.0531.
6-tert-Butyl-4H-thiochromen-4-one (3f): 1-tert-Butyl-4-io-
dobenzene (780 mg, 3.0 mmol) gave 3f; yield: 486 mg
1
General Procedure for the Synthesis 4H-
Thiochromen-4-ones from Aryl Halides
(2.23 mmol, 74%). H NMR (300 MHz, CDCl3): d=8.57 (d,
J=2.0 Hz, 1H), 7.81 (d, J=10.5 Hz, 1H), 7.69 (dd, J=9.0,
6.0 Hz, 1H), 7.56 (d, J=9.0 Hz, 1H), 7.01 (d, J=10.4 Hz,
1H), 1.39 (s, 9H); 13C NMR (75 MHz, CDCl3): d=179.9,
151.4, 137.5, 134.6, 131.9, 129.4, 126.5, 125.7, 124.7, 35.1,
31.2; HR-MS (ESI): m/z=218.0844, calcd. for C13H15OS
[M+H]+: 219.0844.
6-Fluoro-4H-thiochromen-4-one (3j): 1-Fluoro-4-iodoben-
zene (666 mg, 3.0 mmol) gave 3j; yield: 297 mg (1.65 mmol,
5%). 1H NMR (300 MHz, CDCl3): d=8.53 (dd, J=1.8,
1.1 Hz, 1H), 7.84 (d, J=10.5 Hz, 1H), 7.58–7.57 (m, 2H),
7.03 (d, J=10.5 Hz, 1H); 13C NMR (75 MHz, CDCl3): d=
178.5, 137.8, 135.6, 134.4, 133.4, 131.9, 128.3, 128.2, 125.7;
HR-MS (ESI): m/z=180.0123, calcd. for C9H6FOS [M+
H]+: 181.0123.
6-Chloro-4H-thiochromen-4-one (3k): 1-Chloro-4-iodo-
benzene (715 mg, 3.0 mmol) gave 3k; yield: 304 mg
(1.55 mmol, 52%). 1H NMR (300 MHz, CDCl3): d=8.53
(dd, J=1.8, 1.1 Hz, 1H), 7.84 (d, J=10.5 Hz, 1H), 7.58–7.57
(m, 2H), 7.03 (d, J=10.5 Hz, 1H); 13C NMR (75 MHz,
CDCl3): d=178.5, 137.8, 135.6, 134.4, 133.4, 131.9, 128.3,
128.2, 125.7; HR-MS (ESI): m/z=195.9828, calcd. for
C9H6ClOS [M+H]+: 196.9828.
6-Bromo-4H-thiochromen-4-one (3l): 1-Bromo-4-iodoben-
zene (849 mg, 3.0 mmol) gave 3l; yield: 367 mg (1.53 mmol,
51%). 1H NMR (300 MHz, CDCl3): d=8.69 (d, J=2.2 Hz,
1H), 7.84 (d, J=10.5 Hz, 1H), 7.72 (dd, J=8.6, 2.3 Hz, 1H),
7.50 (dd, J=8.6, 0.4 Hz, 1H), 7.03 (d, J=10.5 Hz, 1H);
13C NMR (75 MHz, CDCl3): d=178.4, 137.8, 136.1, 134.6,
133.5, 131.4, 128.2, 125.8, 122.2; HR-MS (ESI): m/z=
239.9323, calcd. for C9H6BrOS [M+H]+: 240.9323.
In
a
25-mL flask were charged aryl halide (612 mg,
(PPh3)2Cl2
3.0 mmol), Na2S·5H2O (1.01 g, 6.0 mmol), Pd
AHCTUNGTRENNUNG
(52.6 mg, 0.225 mmol), dppb (64.0 mg, 0.25 mmol) and the
misture was stirred with DMSO for 5 min. And then DBU
(913 mg, 6.0 mmol) and propiolic acid (252 mg, 3.6 mmol) or
butynoic acid (302 mg, 3.6 mmol) were reacted at 508C for
12 h. After cooling, the mixture was poured into dichloro-
methane (50.0 mL) and washed with water (3ꢁ25.0 mL),
brine (3ꢁ25.0 mL), and then dried over MgSO4 and passed
through a celite pad. Evaporation of the solvent under re-
duced pressure provided the crude product. The crude prod-
uct was treated with sulfuric acid (5 mL) without any further
purification at 1008C for 90 min. After cooling, the reaction
mixture was poured into ice. Then it was extacted with ethyl
acetate (20. 0 mLꢁ3) and washed with water (3ꢁ25.0 mL)
and then dried over MgSO4. Evaporation of the solvent
under reduced pressure provided the crude product, which
was purified by column chromatography (hexane:EtOAc=
4:1) to afford the final product.
4H-Thiochromen-4-one (3a):[20] Iodobenzene (612 mg,
3.0 mmol) gave 3a; yield: 389 mg (2.40 mmol, 80%).
1H NMR (300 MHz, CDCl3): d=8.51 (m, 1H), 7.83 (d, J=
10.5 Hz, 1H), 7.63-7.53 (m, 3H), 7.02 (d, J=10.5 Hz, 1H);
13C NMR (75 MHz, CDCl3): d=179.7, 137.8, 137.5, 132.3,
131.4, 128.7, 127.8, 126.7, 125.9; MS (EI): m/z=162 (M+,
100), 108 (50), 69 (30), 50 (15).
7-Methyl-4H-thiochromen-4-one
(3b):
3-Iodotoluene
(654 mg, 3.0 mmol) gave 3b; yield: 370 mg (2.10 mmol,
1
70%). H NMR (300 MHz, CDCl3): d=8.44 (d, J=8.3 Hz,
6-(Trifluoromethyl)-4H-thiochromen-4-one (3n): 1-Iodo-4-
(trifluoromethyl)benzene (816 mg, 3.0 mmol) gave 3n; yield:
504 mg (2.19 mmol, 73%). H NMR (300 MHz, CDCl3): d=
1H), 7.78 (d, J=10.5 Hz, 1H), 7.41–7.35 (m, 2H), 6.98 (d,
J=10.5 Hz, 1H), 2.47 (s, 3H); 13C NMR (75 MHz, CDCl3):
d=179.7, 142.3, 137.6, 137.4, 130.1, 129.4, 128.6, 126.4, 125.9,
1
Adv. Synth. Catal. 2013, 355, 1160 – 1168
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
1167

Thiruvengadam Palani et al.
FULL PAPERS
8.80 (m, 1H), 7.88–7.73 (m, 3H), 7.07 (d, J=10.5 Hz, 1H);
13C NMR (126 MHz, CDCl3): d=178.7, 155.0, 141.0, 137.9,
[7] a) J. W. Mcdonald, J. L. Corbin, W. E. Newton, Inorg.
Chem. 1976, 15, 2056; b) H. Kuniyasu, A. Ogawa, K. I.
Sato, I. Ryu, N. Kambe, N. Sonoda, J. Am. Chem. Soc.
1992, 114, 5902; c) J. E. Backvall, A. Ericsson, J. Org.
Chem. 1994, 59, 5850; U. Koelle, C. Rietmann, J. Tjoe,
T. Wagner, U. Englert, Organometallics 1995, 14, 703;
d) A. Ogawa, T. Ikeda, K. Kimura, T. Hirao, J. Am.
Chem. Soc. 1999, 121, 5108; e) K. Sugoh, H. Kuniyasu,
T. Sugae, A. Ohtaka, Y. Takai, A. Tanaka, C. Machino,
N. Kambe, H. Kurosawa, J. Am. Chem. Soc. 2001, 123,
5108; f) L.-B. Han, C. Zhang, H. Yazawa, S. Shimada,
J. Am. Chem. Soc. 2004, 126, 5080; g) V. P. Ananikov,
D. A. Malyshev, I. P. Beletskaya, G. G. Aleksandrov,
I. L. Eremenko, Adv. Synth. Catal. 2005, 347, 1993;
h) M. Yoshiyuki, H. Seino, Y. Mizobe, J. Organomet.
Chem. 2006, 691, 3157; i) V. P. Ananikov, N. V. Orlov,
I. P. Beletskaya, Organometallics 2006, 25, 1970;
j) D. A. Malyshev, N. M. Scott, N. Marion, E. D. Ste-
vens, V. P. Ananikov, I. P. Beletskaya, S. P. Nolan, Orga-
nometallics 2006, 25, 4462; k) A. Corma, C. Gonzꢂlez-
Aellano, M. Igesias, F. Sꢂnchez, Appl.Catal. A: 2010,
375, 49.
[8] a) S. Burling, L. D. Field, B. A. Messerle, K. Q. Vuong,
P. Turner, Dalton Trans. 2003, 4181; b) L. D. Field,
B. A. Messerle, K. Q. Vuong, P. Turner, Dalton Trans.
2009, 3599.
[9] A. Kondoh, H. Yorimitsu, K. Oshima, Org. Lett. 2007,
9, 1383.
[10] a) Z.-L. Wang, R.-Y. Tang, P.-S. Luo, C.-L. Deng, P.
Zhong, J.-H. Li, Tetrahedron 2008, 64, 10670; b) S.
Ranjit, Z. Duan, P. Zhang, X. Liu, Org. Lett. 2010, 12,
4134; c) S. N. Riduan, J. Y. Ying, Y. Zhang, Org. Lett.
2012, 14, 1780.
[11] a) W. E. Truce, J. A. Simms, M. M. Boudakian, J. Am.
Chem. Soc. 1956, 78, 695; b) W. E. Truce, J. A. Simms,
J. Am. Chem. Soc. 1956, 78, 2756.
132.3, 127.7, 127.4 (q, JC,F =3.4 Hz), 126.4, 126.2. (q, JC,F
=
12.6 Hz); HR-MS (ESI): m/z=230.0091, calcd. for
C10H6F3OS [M+H]+: 231.0091.
6-Chloro-2-methyl-4H-thiochromen-4-one
G
1-
Chloro-4-iodobenzene (715 mg, 3.0 mmol) and 2-butynoic
acid (503 mg, 6.0 mmol) gave 3k-Me as a reddish orange
1
solid; yield: 202 mg (0.96 mmol, 32%). H NMR (300 MHz,
CDCl3): d=8.48 (dd, J=2.2, 0.5 Hz, 1H), 7.53 (m, 2H), 6.85
(dd, J=2.1, 1.0 Hz, 1H), 2.47 (d, J=1.1 Hz, 3H); 13C NMR
(75 MHz, CDCl3): d=179.4, 151.5, 135.7, 134.0, 131.9, 131.8,
128.2, 127.4, 124.8, 23.3; HR-MS (ESI): m/z=210.9982,
calcd. for C10H8ClOS [M+H]+: 210.9984.
Acknowledgements
This research was supported by Nano.Material Technology
Development Program through the National Research Foun-
dation of Korea (NRF) funded by the Ministry of Education,
Science
and
Technology
(grant
number
2012M3A7B4049655).
References
[1] a) B. M. Trost, A. C. Lavoie, J. Am. Chem. Soc. 1983,
105, 5075; b) R. D. Miller, R. Hassig, Tetrahedron Lett.
1985, 26, 2395; c) J. V. Comasseto, L. W. Ling, N. Pet-
ragnani, H. A. Stefani, Synthesis 1997, 373; d) H.
Mizuno, K. Domon, K. Masuya, K. Tanino, I. Kuwaji-
ma, J. Org. Chem. 1999, 64, 2648; e) H. Yamaguchi,
Y. J. Minoura, Appl. Polym. Sci. 2003, 15, 1869; f) E. D.
Holly, J. Polym. Sci. 2003, 36, 329.
[2] a) E. Marcantoni, M. Massaccesi, M. Petrini, G. Bartoli,
M. C. Bellucci, M. Bosco, L. Sambri, J. Org. Chem.
2000, 65, 4553; b) M. Cerutia, G. Ballianob, F. Roccob,
P. Millab, S. Arpiccob, L. Catte, F. Viola, Lipids 2001,
36, 629; c) H. S. Sader, D. M. Johnson, R. N. Jones, An-
timicrob. Agents Chemother. 2004, 48, 53.
[12] A. Kondoh, K. Takami, H. Yorimitsu, K. Oshima, J.
Org. Chem. 2005, 70, 6468.
[13] C. W. Downey, S. Craciun, A. M. Neferu, C. A. Vivelo,
C. J. Mueller, B. C. Southall, S. Corsi, E. W. Etchill,
R. J. Sault, Tetrahedron Lett. 2012, 53, 5763.
[3] a) T. Kondo, T. Mitsudo, Chem. Rev. 2000, 100, 3205;
b) N. V. Zyk, E. K. Beloglazkina, M. A. Belova, N. S.
Dubinina, Russ. Chem. Rev. 2003, 72, 769.
[14] a) N. Park, K. Park, M. Jang, S. Lee, J. Org. Chem.
2011, 76, 4371; b) N. Pak, Y. Heo, M. R. Kumar, Y.
Kim, K. H. Song, S. Lee, Eur. J. Org. Chem. 2012, 1984.
[15] a) J. Moon, M. Jeong, H. Nam, J. Ju, J. H. Moon, H. M.
Jung, S. Lee, Org. Lett. 2008, 10, 945; b) K. Park, G.
Bae, J. Moon, J. Choe, K. H. Song, S. Lee, J. Org.
Chem. 2010, 75, 6244.
[16] a) N. G. Li, Z. H. Shi, Y. P. Tang, H. Y. Ma, J. P. Yang,
B. Q. Li, Z. J. Wang, S. L. Song, J. A. Duan, J. Hetero-
cycl. Chem. 2010, 47, 785; b) F. C. Fuchs, G. A. Eller,
W. Holzer, Molecules 2009, 14, 3814.
[4] a) T. Kumamoto, K. Hosoi, T. Mukaiyam, Bull. Chem.
Soc. Jpn. 1968, 41, 2742; b) E. Stephan, A. Olaru, G.
Jaouen, Tetrahedron Lett. 1999, 40, 8571; c) V. Aucagne,
A. Tatibouet, P. Rollin, Tetrahedron 2004, 60, 1817.
[5] a) H. J. Cristau, B. Chabaud, R. Labaudiniere, H.
Christol, J. Org. Chem. 1986, 51, 875; b) T. Ogawa, K.
Hayami, H. Suzuki, Chem. Lett. 1989, 769; c) C. G.
Bates, P. Saejueng, M. Q. Doherty, D. Venkataraman,
Org. Lett. 2004, 6, 5005.
[6] a) K. Griesbaum, Angew. Chem. 1970, 82, 276; Angew.
Chem. Int. Ed. Engl. 1970, 9, 273; b) Y. Ichinose, K.
Wakamatsu, K. Nozaki, J.-L. Birbaum, K. Oshima, K.
Utimoto, Chem. Lett. 1987, 1647; c) L. Benati, L. Ca-
pella, P. C. Montevecchi, P. Spagnolo, J. Org. Chem.
1994, 59, 2818; d) L. Benati, L. Capella, P. C. Monte-
vecchi, P. Spagnolo, J. Chem. Soc. Perkin Trans. 1 1995,
1035; e) Z. Duan, S. Ranjit, P. Zhang, X. Liu, Org. Lett.
2010, 12, 2430.
[17] We failed to obtain intermediate A under dark condi-
tions. It is known that sodium propiolate is light sensi-
tive. See: J. Yang, K. Hong, P. V. Bonnesen, J. Label
Compd. Radiopharm. 2011, 54, 743.
[18] M. Toyofuku, S. Fujiwara, T. Shin-ike, H. Kuniyasu, N.
Kambe, J. Am. Chem. Soc. 2008, 130, 10504.
[19] W. E. Truce, R. F. Heine, J. Am. Chem. Soc. 1957, 79,
1770.
[20] B. Willy, W. Frank, T. J. J. Muller, Org. Biomol. Chem.
2010, 8, 90.
1168
asc.wiley-vch.de
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2013, 355, 1160 – 1168