A cyclization-carbonylation-cyclization coupling reaction of (ortho-alkynyl phenyl) (methoxymethyl) sulfides with the palladium(ii)-bisoxazoline catalyst

Article abstract of DOI:10.1039/c4ob00299g

A cyclization-carbonylation-cyclization coupling reaction (CCC-coupling reaction) of (o-alkynylphenyl) (methoxymethyl) sulfides, catalyzed by (box)Pd^II complexes, afforded symmetrical ketones bearing two benzo[b]thiophene groups in good to excellent yields. This method is applicable to a broad range of substrates. the Partner Organisations 2014.

Full text of DOI:10.1039/c4ob00299g

Organic &
Biomolecular Chemistry
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PAPER
A cyclization–carbonylation–cyclization
coupling reaction of (ortho-alkynyl phenyl)
(methoxymethyl) sulfides with the
palladium(II)-bisoxazoline catalyst†
Cite this: Org. Biomol. Chem., 2014,
12, 3380
Yiyun Jiang, Taichi Kusakabe, Keisuke Takahashi and Keisuke Kato*
Received 10th February 2014,
Accepted 18th March 2014
A cyclization–carbonylation–cyclization coupling reaction (CCC-coupling reaction) of (o-alkynylphenyl)
(methoxymethyl) sulfides, catalyzed by (box)PdII complexes, afforded symmetrical ketones bearing
two benzo[b]thiophene groups in good to excellent yields. This method is applicable to a broad range of
substrates.
DOI: 10.1039/c4ob00299g
www.rsc.org/obc
systems.4 Among these, ortho-alkynyl phenyl sulfides are good
precursors for the synthesis of benzo[b]thiophenes.5
Introduction
Benzo[b]thiophenes have been recognized to be an important
Recently, we reported that the cyclization–carbonylation–
class of S-heterocycles in pharmaceutical sciences.1 They cyclization coupling reaction (CCC-coupling reaction) of pro-
exhibit various interesting biological properties, such as anti- pargylic compounds using palladium(II)-bisoxazoline (box)
tumor,2a antipsychotic,2b anti-inflammatory,2c antiallergic,2d complexes afforded symmetrical ketones bearing two oxazoles,
and antimicrobial activities2e and the inhibition of tubulin cyclic orthoesters, oxabicyclic groups, quinolines, benzofurans,
polymerization2f (Fig. 1). Diarylketones are also frequently oxazolines and pyrazoles (Scheme 1).6 The CCC-coupling is a
found in natural products and pharmaceuticals,3 e.g., suprofen two-component (three molecules) coupling reaction based on
(non-steroidal anti-inflammatory), raloxifene (selective estro- double intramolecular cyclization of propargylic compounds
gen receptor modulator used for the treatment of osteo- bearing nucleophiles in conjunction with incorporation of
porosis), benzbromarone (antipodagric) and amiodarone carbon monoxide. Two C–X bonds and two C–C bonds are
(antiarrhythmic). A variety of heterocycles can be synthesized formed in one-step reactions. In this transformation, the box
by transition-metal-catalyzed cyclization of unsaturated ligand plays an important role in the coordination of a second
molecule in intermediate A, and methanolysis of the acyl palla-
dium should be suppressed by coordination of this second
molecule. To extend the generality of the CCC-coupling
reaction, we investigated the (box)PdII-catalyzed carbonyla-
tion reaction of (o-alkynylphenyl) (methoxymethyl) sulfides 1
(Tables 1 and 2).
Fig. 1 Structures of biologically active benzo[b]thiophenes and
diarylketones.
Faculty of Pharmaceutical Sciences, Toho University, 2-2-1 Miyama, Funabashi,
Chiba 274-8510, Japan. E-mail: kkk@phar.toho-u.ac.jp; Fax: +81 474 721 805;
Tel: +81 474 721 805
†Electronic supplementary information (ESI) available: Experimental procedures
Scheme 1 Cyclization–carbonylation–cyclization-coupling
reaction
and characterization data. See DOI: 10.1039/c4ob00299g
(CCC-coupling reaction) of propargylic compounds.
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Table 1 Optimization of the CCC-coupling reaction of 1a
Fig. 2 Ligands for Table 1.
Temp (°C),
time (h)
Yield of
2a (%)
Yield of
3a (%)
Entry
Catalyst
1
Pd(tfa)2
−20 to −10, 45
−20 to −10, 45
−20 to −10, 24
−30, 48
49
41
—
—
86
85
Quant.
77
70
11
18
28
—
Trace
10
—
2
2
7
(1.5 equiv.) in methanol under a carbon monoxide atmosphere
(balloon) generated the dimeric ketone 2a in 49% yield along
with 11% yield of 3a (Table 1, entry 1). These products were
easily separated by silica gel chromatography. The use of 2,2′-
bipyridine complexes also gave poor results (Table 1, entries 2
and 3). The phosphine complexes Pd(PPh3)4, [PdCl2(PPh3)2]
and Pd–C (Table 1, entry 4) did not show catalytic activity.
Next, an attempt was made to use the box ligands L1–L5
(Table 1, entries 5–9, Fig. 2). In our previous research,6,7 substi-
tuents at the C4 position of the box ligands played an impor-
tant role in promoting the attempted reactions. In this case,
however, all box ligands exhibited moderate to good activity.
Among them, ( )-Phbox ligand L3 gave the best result (Table 1,
entry 7). In terms of the palladium counteranion, switching
from trifluoroacetate to acetate caused a decrease in the yields
(Table 1, entry 10). The Lewis acidity of palladium(II) is
expected to decrease with increasing nucleophilicity of its
counteranion.9 Chloride showed a moderate catalytic activity
(Table 1, entry 11). Furthermore, THF and CH2Cl2 were not
suitable as solvents, as the reaction did not proceed when they
were used.
2
[PdCl2(2,2′-bipy)]a
[Pd(tfa)2(2,2′-bipy)]b
5% Pd–C
3c
4c
5
Pd(tfa)2/L1d
−30, 26
6
7
8
[Pd(tfa)2(L2)]b
[Pd(tfa)2(L3)]b
Pd(tfa)2/L4d
−30 to −10, 19
−30 to −10, 31
−20 to −10, 48
−20 to −10, 48
−20 to −10, 48
−30 to −10, 72
9
Pd(tfa)2/L5d
10e
11
[Pd(OAc)2(L3)]b
[PdCl2(L3)]b
58
86
Trace
a Commercially available. b The isolated complex was employed.
c Recovery 57–93%. d Pd(tfa)2 5 mol% and L1 7.5 mol%. e Recovery 20%.
Table 2 Substrate scope of the CCC-coupling reaction
Temp (°C),
Entry R1
R2 R3
R4 time (h)
Yield (%)
Having elucidated the optimum conditions for the reaction,
we then employed a variety of (o-alkynylphenyl) (methoxy-
methyl) sulfides 1 in the CCC-coupling reaction (Table 2).
First, the reaction of substrates derived from (o-iodophenyl)
(methoxymethyl) sulfides and ArCuCH (R1 = Ar, R2–R4 = H)
was investigated (Table 2, entries 1–8). The substrates 1b–1d
bearing both electron-donating and electron-withdrawing
substituents gave good results, similar to that of the parent
substrate 1a (Table 2, entries 2–4). Three kinds of halogen
substituents (F, Cl, and Br) on the phenyl ring and a thiophene
ring in the alkyne terminus were tolerated under the reaction
conditions (Table 2, entries 5–8). Replacement of the aryl
groups at the alkyne terminus with alkyl groups also led to the
desired 2i–2k in good yield (Table 2, entries 9–11). A free
hydroxyl group in the alkyne terminus was also tolerated
under the reaction conditions, providing 2l in 87% yield
(Table 2, entry 12). It is noteworthy that the terminal acetylene
1m was transformed to the corresponding ketone 2m in 80%
yield (Table 2, entry 13). To further broaden the substrate
scope of the CCC-coupling reaction, the reactions of substrates
bearing R2–R4 substituents were investigated (Table 2, entries
1
2
3
4
5
6
7
8
Ph
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
Me
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
Cl
Cl
−30 to −10, 31
2a: quant.
2b: 82
2c: 88
2d: 88
2e: 84
4-MePh
4-MeOPh
4-CF3Ph
4-FPh
4-BrPh
4-ClPh
3-Thienyl
Phenethyl
Octyl
Cyclopropyl
HO(CH2)9
H
Ph
4-tBuPh
Ph
−30 to −10, 72
−40 to −30, 31
−40 to −20, 78
−30 to −10, 72
−35 to −25, 114 2f: 89
−30 to −10, 72
−40 to −20, 68
−30, 42
2g: 84
2h: 84
2i: 95
2j: 80
2k: 86
2l: 87
2m: 80
2n: 83
2o: 86
2p: 99
2q: 82
2r: 75
9
10
11
12
13
14
15
16
17
18
19
20
21
−30, 24
−30, 48
−30 to −20, 72
−20 to rt, 72
−30 to −20, 72
−30 to −20, 40
Me −30, 24
Me −30 to −20, 44
H
H
H
H
Ph
Ph
H
MeO
MeO
MeO
MeO
−30, 74
4-MeOPh
3-HOPh
3,5-(MeO)2Ph
−30 to −20, 144 2s: 97
−30, 144
2t: 77
2u: 78
−30 to −20, 31
Results and discussion
The (o-alkynylphenyl) (methoxymethyl) sulfides 1 were pre- 14–21). For substrates 1n–1q bearing a methyl group or Cl sub-
pared from known o-iodoanilines by modification of a pub- stituents in an aromatic moiety, the reaction proceeded well
lished procedure.8 Initially, we selected 1a as a standard (Table 2, entries 14–17). The substrates 1r–1u bearing electron-
substrate to search for potential catalysts (Table 1). The donating groups afforded slightly lower yields (75–78%) of the
reaction of 1a with Pd(tfa)2 (5 mol%) and p-benzoquinone products except in the case of 1s (Table 2, entries 18–21).
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Preparation of box-palladium complexes
The box ligands L1–L3 and palladium complexes [Pd(tfa)2(2,2′-
bipy)], [Pd(tfa)2(L2)], [Pd(tfa)2(L3)] and [PdCl2(L3)] were pre-
pared according to a literature method.6a,d,10
General procedure for the CCC-coupling reaction of (o-alkynyl-
phenyl) (methoxymethyl) sulfides 1. A 30 mL two-necked
round-bottom flask containing a magnetic stirring bar, (o-alkynyl-
phenyl) (methoxymethyl) sulfides 1 (0.4 mmol), p-benzo-
quinone (65 mg, 0.6 mmol) and MeOH (3 mL) was fitted with
a rubber septum and a three-way stopcock connected to a
balloon filled with carbon monoxide. The apparatus was
purged with carbon monoxide by pump-filling via the three-
way stopcock. A MeOH (1 mL) suspension of [Pd(tfa)2(L3)]
(13.3 mg, 0.02 mmol) was added to the stirred solution via a
syringe at an appropriate temperature. The remaining catalyst
was washed in MeOH (1 mL) twice, and stirred for the period
of time. In most cases, the dimeric ketones precipitated from
the reaction mixture. The resulting precipitate was collected by
filtration and washed with cold MeOH (1.5 mL × 2) to yield
dimeric ketones 2. As small amounts of 2 (and 3a, see Table 1)
still remained in the filtrate, the filtrate was diluted with
CH2Cl2 (50 mL) and washed with 5% NaOH (40 mL). The
aqueous layer was extracted with CH2Cl2 (25 mL), and the com-
bined organic layers were dried over MgSO4 and concentrated
in vacuo. The crude product was purified by column chromato-
graphy on silica gel. The fraction eluted with hexane–EtOAc
(100/1) afforded small amounts of dimeric ketones 2 (and
monomeric ester 3a (only hexane)).
Bis(2-phenylbenzo[b]thiophen-3-yl)methanone 2a. 100%
Yield (86.4 mg), white solid, mp 193–195 °C, 1H NMR
(400 MHz, CDCl3) δ 6.86–6.90 (4H, m), 6.99–7.04 (6H, m), 7.36
(2H, dt, J = 1.2, 8.0 Hz), 7.51 (2H, dt, J = 1.2, 8.0 Hz), 7.65 (2H,
br-d, J = 8.0 Hz), 8.33 (2H, br-d, J = 8.0 Hz); 13C NMR
(100 MHz, CDCl3) δ 121.4 (2C), 123.8 (2C), 125.0 (2C), 125.6
(2C), 127.5 (4C), 128.5 (2C), 129.2 (4C), 132.6 (2C), 132.9 (2C),
138.4 (2C), 140.1 (2C), 150.8 (2C), 189.4; IR (KBr) 1633, 1458,
1432, 751, 691 cm−1; HRMS-EI: m/z: [M+] calcd for C29H18OS2
446.0799, found 446.0801.
Scheme 2 A plausible mechanism for the cyclization–carbonylation–
cyclization-coupling reaction (CCC-coupling reaction) of (o-alkynyl-
phenyl) (methoxymethyl) sulfides 1.
A plausible mechanism for the reaction of 1 is shown in
Scheme 2. A nucleophilic attack by the sulfur atom at the electro-
philically activated triple bond was followed by CO insertion
to produce the acyl palladium intermediate A. The methoxy-
methyl group may be removed by acetal exchange (or hydro-
lysis) during the formation of intermediate A. Coordination of
the triple bond of a second molecule induces the second cycli-
zation, and reductive elimination then leads to the formation
of a ketone bearing two heterocyclic groups. We believe that
the box ligand enhances the π-electrophilicity of palladium(II),7
and thus promotes coordination of the second triple bond to
the acyl palladium intermediate A, leading to the dimerization
reaction.
Conclusions
In conclusion, we carried out cyclization–carbonylation–cycli-
zation coupling reactions (CCC-coupling reactions) of (o-alkynyl-
phenyl) (methoxymethyl) sulfides 1 catalyzed by (box)PdII
complexes. Symmetrical ketones possessing two benzo[b]thio-
phene groups were obtained in good to excellent yields. The
reaction was general for a wide range of (o-alkynylphenyl) (meth-
oxymethyl) sulfides 1. We are currently investigating additional
cascade reactions based on the cyclization–carbonylation–
cyclization strategy presented here for the synthesis of other
types of ketones containing two heterocyclic groups.
2-Phenylbenzo[b]thiophene (3a) was a known compound.11
Bis[2-(4-methylphenyl)benzo[b]thiophen-3-yl]methanone
2b. 82% Yield (79.5 mg), white solid, mp 227 °C, 1H NMR
(400 MHz, CDCl3) δ 2.12 (6H, s), 6.66–6.68 (4H, m), 6.87–6.90
(4H, m), 7.34 (2H, dt, J = 1.2, 8.0 Hz), 7.49 (2H, dt, J = 1.2, 8.0
Hz), 7.63 (2H, br-d, J = 8.0 Hz), 8.28 (2H, br-d, J = 8.0 Hz); 13C
NMR (100 MHz, CDCl3) δ 21.1 (2C), 121.3 (2C), 123.7 (2C),
124.7 (2C), 125.4 (2C), 128.2 (4C), 129.0 (4C), 129.8 (2C), 132.5
(2C), 138.3 (2C), 138.5 (2C), 140.1 (2C), 150.9 (2C), 189.6; IR
(KBr) 1643, 1531, 676 cm−1; HRMS-EI: m/z: [M+] calcd for
C31H22OS2 474.1112, found 474.1112.
Bis[2-(4-methoxyphenyl)benzo[b]thiophen-3-yl]methanone
2c. 88% Yield (89.2 mg), brown solid, mp 198–201 °C, 1H
NMR (400 MHz, CDCl3) δ 3.58 (6H, s), 6.35–6.39 (4H, m),
6.90–6.94 (4H, m), 7.34 (2H, dt, J = 1.2, 8.0 Hz), 7.49 (2H, dt,
J = 1.2, 8.0 Hz), 7.63 (2H, br-d, J = 8.0 Hz), 8.30 (2H, br-d, J =
8.0 Hz); 13C NMR (100 MHz, CDCl3) δ 55.2 (2C), 113.0 (4C),
Experimental section
General information
See ESI† for general experimental details as well as procedures
for the preparation and characterization of all precursors and
products.
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121.3 (2C), 123.6 (2C), 124.7 (2C), 125.2 (2C), 125.5 (2C), 130.5 770, 755 cm−1; HRMS-EI m/z [M+] calcd for C25H14OS4
(4C), 132.0 (2C), 138.3 (2C), 140.3 (2C), 150.8 (2C), 159.8 (2C), 457.9928, found 457.9929.
Bis[2-(2-phenylethyl)benzo[b]thiophen-3-yl]methanone
189.7; IR (KBr) 1631, 1604, 1458, 1257, 1180, 1086 cm−1
;
1
HRMS-EI: m/z: [M+] calcd for C31H22O3S2 506.1011, found
2i. 95% Yield (95.5 mg), yellow oil, H NMR (400 MHz, CDCl3)
δ 2.83–2.93 (4H, m), 3.04–3.12 (4H, m), 6.92–6.95 (4H, m),
506.1011.
Bis[2-(4-trifluoromethylphenyl)benzo[b]thiophen-3-yl]- 7.10–7.19 (6H, m), 7.24 (2H, dt, J = 1.2, 8.0 Hz), 7.31 (2H, dt,
methanone 2d. 88% Yield (102.5 mg), white solid, mp J = 1.2, 7.2 Hz), 7.57 (2H, br-d, J = 8.0 Hz), 7.80 (2H, br-d, J =
233–235 °C, 1H NMR (400 MHz, CDCl3) δ 7.10–7.15 (8H, m), 8.0 Hz); 13C NMR (100 MHz, CDCl3) δ 31.9 (2C), 37.9 (2C), 122.0
7.43 (2H, dt, J = 0.8, 8.0 Hz), 7.56 (2H, dt, J = 0.8, 8.0 Hz), 7.69 (2C), 123.3 (2C), 124.7 (2C), 125.2 (2C), 126.2 (2C), 128.31 (4C),
(2H, br-d, J = 8.0 Hz), 8.29 (2H, br-d, J = 8.0 Hz); 13C NMR 128.33 (2C), 128.4 (4C), 133.9 (2C), 138.1 (2C), 140.3 (2C), 152.7
1
(100 MHz, CDCl3) δ 121.7 (2C), 123.6 (2C, q, JC–F = 270.6 Hz), (2C), 188.3; IR (KBr) 2923, 1636, 1455, 1432, 1188, 745,
3
123.8 (2C), 124.5 (4C, q, JC–F = 3.9 Hz), 125.8 (2C), 126.0 (2C), 698 cm−1; HRMS-EI: m/z [M+] calcd for C33H26OS2 502.1425,
129.3 (4C), 130.4 (2C, q, 2JC–F = 32.4 Hz), 134.2 (2C), 135.9 (2C), found 502.1425.
138.4 (2C), 139.6 (2C), 148.5 (2C), 188.7; IR (KBr) 1646, 1327,
1156, 1123, 1068 cm−1 HRMS-EI: m/z: [M+] calcd for (83.0 mg), pale yellow oil, 1H NMR (400 MHz, CDCl3) δ 0.85
C31H16OF6S2 582.0547, found 582.0547.
(6H, t, J = 7.5 Hz), 1.13–1.26 (20H, m), 1.59–1.60 (4H, m), 2.78
Bis(2-octylbenzo[b]thiophen-3-yl)methanone 2j. 80% Yield
;
Bis[2-(4-fluorophenyl)benzo[b]thiophen-3-yl]methanone (4H, t, J = 7.5 Hz), 7.23–7.31 (4H, m), 7.64 (2H, br-d, J = 7.5
2e. 84% Yield (81.0 mg), white solid, mp 226–227 °C; 1H NMR Hz), 7.78 (2H, br-d, J = 7.5 Hz); 13C NMR (100 MHz, CDCl3) δ
(400 MHz, CDCl3) δ 6.56–6.62 (4H, m), 6.95–7.00 (4H, m), 7.39 14.1 (2C), 22.6 (2C), 29.1 (2C), 29.1 (2C), 29.4 (2C), 29.7 (2C),
(2H, br-d, J = 1.2, 8.0 Hz), 7.52 (2H, dt, J = 1.2, 8.0 Hz), 7.69 31.8 (2C), 32.0 (2C), 121.9 (2C), 123.1 (2C), 124.5 (2C), 125.1
(2H, br-d, J = 8.0 Hz), 8.28 (2H, br-d, J = 8.0 Hz); 13C NMR (2C), 133.6 (2C), 137.7 (2C), 138.4 (2C), 154.1 (2C), 188.7; IR
2
(100 MHz, CDCl3) δ 114.7 (4C, d, JC–F = 21.9 Hz), 121.6 (2C), (KBr): 2924, 2853, 1637, 1457, 1433, 1188 cm−1; HRMS-EI: m/z:
4
123.7 (2C), 125.3 (2C), 125.8 (2C), 128.7 (2C, d, JC–F = 2.9 Hz), [M+] calcd for C33H42OS2 518.2677, found 518.2675.
3
130.8 (4C, d, JC–F = 8.6 Hz), 132.8 (2C), 138.2 (2C), 139.8 (2C),
Bis(2-cyclopropylbenzo[b]thiophen-3-yl)methanone 2k. 86%
149.4 (2C), 162.7 (2C, d, 1JC–F = 248.8 Hz), 189.0; IR (KBr) 1630, Yield (64.4 mg), white solid, mp 260–262 °C; 1H NMR
1490, 1457, 1232 cm−1; HRMS-ESI+ m/z [M + Na]+ calcd for (400 MHz, CDCl3) δ 0.82–0.92 (8H, m), 2.13–2.20 (2H, m),
C29H16F2NaOS2 505.0508, found 505.0536.
7.27–7.33 (4H, m), 7.70–7.74 (2H, m), 7.80–7.84 (2H, m); 13C
Bis[2-(4-bromophenyl)benzo[b]thiophen-3-yl]methanone NMR (100 MHz, CDCl3) δ 11.9 (4C), 12.0 (2C), 121.8 (2C), 123.0
2f. 89% Yield (107.5 mg), yellow solid, mp 268–269 °C; 1H (2C), 124.5 (2C), 125.2 (2C), 134.7 (2C), 136.3 (2C), 138.8 (2C),
NMR (400 MHz, CDCl3) δ 6.85–6.88 (4H, m), 7.00–7.04 (4H, m), 157.2 (2C), 188.6; IR (KBr) 2923, 1629, 1515, 1447, 1358,
7.42 (2H, dt J = 1.2, 8.0 Hz), 7.53 (2H, dt, J = 1.2, 8.0 Hz), 7.72 734 cm−1; HRMS-EI m/z [M+] calcd for C23H18OS2 374.0799,
(2H, br-d, J = 8.0 Hz), 8.26 (2H, br-d, J = 8.0 Hz); 13C NMR found 374.0794.
(100 MHz, CDCl3) δ 121.7 (2C), 123.1 (2C), 123.8 (2C), 125.5
Bis[(2-(9-hydroxynonyl)benzo[b]thiophen-3-yl]methanone
(2C), 125.9 (2C), 130.4 (4C), 130.8 (4C), 131.4 (2C), 133.1 (2C), 2l. 87% Yield (100.6 mg), yellow oil; 1H NMR (400 MHz,
138.3 (2C), 139.8 (2C), 149.2 (2C), 188.8; IR (KBr) 1654, 1627, CDCl3) δ 1.15–1.32 (22H, m), 1.49–1.60 (6H, m), 1.77 (2H, br-s),
465 cm−1; HRMS-EI: m/z [M+] calcd for C29H16Br2OS2 601.9010, 2.79 (4H, t, J = 7.8 Hz), 3.60 (4H, t, J = 6.6 Hz), 7.23–7.32 (4H,
found 601.9008.
m), 7.63 (2H, br-d, J = 7.2 Hz), 7.78 (2H, br-d, J = 7.2 Hz); 13C
Bis[2-(4-chlorophenyl)benzo[b]thiophen-3-yl]methanone NMR (100 MHz, CDCl3) δ 25.6 (2C), 29.0 (2C), 29.3 (4C), 29.4
2g. 84% Yield (86.7 mg), yellow solid, mp 241–242 °C; 1H (2C), 29.7 (2C), 31.9 (2C), 32.7 (2C), 63.0 (2C), 121.9 (2C), 123.1
NMR (400 MHz, CDCl3) δ 6.85–6.88 (4H, m), 6.91–6.95 (4H, m), (2C), 124.5 (2C), 125.1 (2C), 133.6 (2C), 137.6 (2C), 138.3 (2C),
7.41 (2H, dt, J = 1.2, 8.0 Hz), 7.53 (2H, dt, J = 1.2, 8.4 Hz), 7.71 154.1 (2C), 188.7; IR (KBr) 3365, 2925, 2853, 1635, 1434,
(2H, br-d, J = 8.4 Hz), 8.27 (2H, br-d, J = 8.0 Hz); 13C NMR 1065 cm−1; HRMS-EI m/z [M+] calcd for C35H46O3S2 578.2889,
(100 MHz, CDCl3) δ 121.7 (2C), 123.8 (2C), 125.5 (2C), 125.9 found 578.2888.
(2C), 127.8 (4C), 130.2 (4C), 131.0 (2C), 133.1 (2C), 134.8 (2C),
Bis(benzo[b]thiophen-3-yl)methanone 2m.12. 80% Yield
138.3 (2C), 139.8 (2C), 149.2 (2C), 188.8; IR (KBr) 1628, 1431, (47 mg), white solid, mp 167–168 °C, 1H NMR (400 MHz,
1090, 776 cm−1; HRMS-EI: m/z [M+] calcd for C29H16Cl2OS2 CDCl3) δ 7.44–7.54 (4H, m), 7.91 (2H, br-d, J = 8.0 Hz), 8.08
514.0020, found 514.0017.
(2H, s), 8.57 (2H, br-d, J = 8.0 Hz); 13C NMR (100 MHz, CDCl3)
Bis[2-(thiophen-3-yl)benzo[b]thiophen-3-yl]methanone δ 122.4 (2C), 125.0 (2C), 125.7 (2C), 125.7 (2C), 136.4 (2C),
2h. 84% Yield (77.0 mg), dark brown solid, mp 179–181 °C; 1H 136.8 (2C), 137.3 (2C), 140.2 (2C), 184.9; IR (KBr) 1627, 1189,
NMR (400 MHz, CD2Cl2) δ 6.74 (2H, dd, J = 1.2, 4.8 Hz), 6.97 1065, 1550, 677 cm−1; HRMS-EI m/z [M+] calcd for C17H10OS2
(2H, dd, J = 2.8, 4.8 Hz), 7.05 (2H, dd, J = 1.2, 2.8 Hz), 7.40 (2H, 294.0173, found 294.0175.
dt, J = 0.8, 8.0 Hz), 7.48 (2H, dt, J = 0.8, 8.0 Hz), 7.74 (2H, br-d,
Bis(5-chloro-2-phenylbenzo[b]thiophen-3-yl)methanone
J = 8.0 Hz), 8.19 (2H, br-d, J = 8.0 Hz); 13C NMR (100 MHz, 2n. 83% Yield (85.6 mg), white solid, mp 209–211 °C; 1H NMR
CD2Cl2) δ 121.9 (2C), 124.1 (2C), 125.5 (2C), 125.6 (2C), 125.7 (400 MHz, CDCl3) δ = 6.91–6.98 (8H, m), 7.04–7.09 (2H, m),
(2C), 126.0 (2C), 128.5 (2C), 132.6 (2C), 133.5 (2C), 138.6 (2C), 7.34 (2H, dd, J = 2.0, 8.4 Hz), 7.56 (2H, d, J = 8.4 Hz), 8.34 (2H,
139.9 (2C), 145.6 (2C), 188.7; IR (KBr) 1631, 1458, 1191, 840, d, J = 2.0 Hz); 13C NMR (400 MHz, CDCl3) δ = 122.5 (2C), 123.4
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(2C), 125.6 (2C), 127.7 (4C), 129.0 (2C), 129.2 (6C), 131.8 (2C), 8.8 Hz), 7.43 (2H, d, J = 2.4 Hz), 7.97 (2H, d, J = 8.8 Hz), 9.34
132.1 (2C), 136.4 (2C), 141.0 (2C), 152.7 (2C), 188.5; IR (KBr) (2H, s); 13C NMR (100 MHz, DMSO-d6) δ = 55.5 (2C), 104.4
1622, 1423, 1150, 1071, 747 cm−1; HRMS-EI m/z: [M+] calcd for (2C), 115.2 (2C), 115.3 (2C), 115.5 (2C), 120.0 (2C), 124.1 (2C),
C29H16Cl2OS2 514.0020, found 514.0026.
128.5 (2C), 132.1 (2C), 133.4 (2C), 133.5 (2C), 139.1 (2C), 147.4
Bis[2-(4-tert-butylphenyl)-5-chlorobenzo[b]thiophen-3-yl]- (2C), 156.7 (2C), 157.2 (2C), 188.7; IR (KBr) 3372, 1602, 1592,
methanone 2o. 86% Yield (108.0 mg), white solid, mp 1238, 1060, 771 cm−1; HRMS-EI: m/z [M+] calcd for C31H22O5S2
1
280–281 °C; H NMR (400 MHz, CDCl3) δ = 1.13 (18H, s), 6.89 538.0909, found 538.0907.
(8H, s), 7.33 (2H, dd, J = 2.0, 8.4 Hz), 7.50 (2H, br-d, J = 8.4 Hz),
Bis[2-(3,5-dimethoxyphenyl)-6-methoxybenzo[b]thiophen-
8.30 (2H, br-d, J = 2.0 Hz); 13C NMR (100 MHz, CDCl3): δ = 30.9 3-yl]methanone 2u. 78% Yield (97.7 mg), yellow solid, mp
1
(6C), 34.4 (2C), 122.3 (2C), 123.2 (2C), 124.5 (4C), 125.3 (2C), 117–118 °C; H NMR (400 MHz, CDCl3) δ = 3.46 (12H, s), 3.89
129.0 (4C), 129.2 (2C), 131.9 (2C), 132.0 (2C), 136.3 (2C), 141.2 (6H, s), 6.12 (4H, d, J = 2.4 Hz), 6.19 (2H, t, J = 2.4 Hz), 7.11
(2C), 152.2 (2C), 152.8 (2C), 188.9; IR (KBr) 2957, 1642, 1627, (2H, dd, J = 2.4, 8.8 Hz), 7.16 (2H, d, J = 2.4 Hz), 8.27 (2H, d, J =
1549, 1426, 1079, 675 cm−1; HRMS-ESI+ m/z [M + Na]+ calcd 8.8 Hz); 13C NMR (100 MHz, CDCl3) δ = 55.0 (4C), 55.6 (2C),
for C37H32Cl2NaOS2 649.1169, found 649.1191.
101.3 (2C), 104.1 (2C), 107.4 (4C), 115.3 (2C), 125.0 (2C), 131.9
Bis(5-methyl-2-phenylbenzo[b]thiophen-3-yl)methanone (2C), 134.1 (2C), 134.5 (2C), 139.8 (2C), 148.8 (2C), 157.8 (2C),
2p. 99% Yield (94.9 mg), brown solid, mp 170–172 °C; 1H 159.8 (4C), 188.9; IR (KBr) 1618, 1597, 1457, 1271, 1203, 1152,
NMR (400 MHz, CDCl3) δ = 2.56 (6H, s), 6.86–6.90 (4H, m), 1066 cm−1; HRMS-ESI+ m/z [M + Na]+ calcd for C35H30NaO7S2
6.96–7.00 (4H, m), 7.00–7.05 (2H, m), 7.19 (2H, br-d, J = 8.4 649.1331, found 649.1340.
Hz), 7.52 (2H, d, J = 8.4 Hz), 8.16 (2H, br-s); 13C NMR
(100 MHz, CDCl3) δ = 21.8 (2C), 121.0 (2C), 123.7 (2C), 126.7
(2C), 127.5 (4C), 128.4 (2C), 129.2 (4C), 132.4 (2C), 132.8 (2C),
Acknowledgements
135.4 (2C), 135.7 (2C), 140.4 (2C), 151.1 (2C), 189.5; IR (KBr)
1636, 1509, 1439, 758, 743, 693 cm−1; HRMS-EI: m/z [M+] calcd This work was supported by a JSPS KAKENHI grant (no.
for C31H22OS2 474.1112, found 474.1112.
24590026).
Bis(5,7-dimethyl-2-phenylbenzo[b]thiophen-3-yl)methanone
2q. 82% Yield (83.1 mg), pale yellow solid, mp 229–231 °C; 1H
NMR (400 MHz, CDCl3) δ = 2.40 (6H, s), 2.52 (6H, s), 6.86–6.90
(4H, m), 6.98–7.03 (8H, m), 7.99 (2H, m); 13C NMR (100 MHz,
CDCl3) δ = 20.0 (2C), 21.7 (2C), 121.4 (2C), 127.0 (2C), 127.4
(4C), 128.2 (2C), 129.2 (4C), 130.4 (2C), 133.0 (2C), 133.0 (2C),
135.8 (2C), 135.9 (2C), 140.3 (2C), 150.5 (2C), 189.8; IR (KBr)
1614, 1364, 1270, 756, 717, 699 cm−1; HRMS-EI m/z: [M+] calcd
for C33H26OS2 502.1425, found 502.1424.
Notes and references
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Bis(6-methoxy-2-phenylbenzo[b]thiophen-3-yl)methanone
1
2r. 75% Yield (76.1 mg), pale yellow solid, mp 224–225 °C; H
NMR (400 MHz, CDCl3) δ = 3.89 (6H, s), 6.89–6.98 (8H, m),
7.02–7.07 (2H, m), 7.11–7.14 (4H, m), 8.19 (2H, br-d, J = 8.4
Hz); 13C NMR (100 MHz, CDCl3) δ = 55.6 (2C), 104.0 (2C), 115.2
(2C), 124.6 (2C), 127.5 (4C), 128.3 (2C), 129.2 (4C), 132.4 (2C),
132.7 (2C), 134.3 (2C), 139.9 (2C), 148.4 (2C), 157.7 (2C), 189.4;
IR (KBr) 1624, 1601, 1474, 1252, 1052, 744 cm−1; HRMS-EI: m/z
[M+] calcd for C31H22O3S2 506.1011, found 506.1009.
Bis[6-methoxy-2-(4-methoxyphenyl)benzo[b]thiophen-3-yl]-
methanone 2s. 97% Yield (109.9 mg), yellow powder, mp
1
215–217 °C; H NMR (400 MHz, CDCl3) δ = 3.64 (6H, s), 3.88
(6H, s), 6.41–6.44 (4H, m), 6.88–6.92 (4H, m), 7.09–7.12 (4H,
m), 8.15–8.17 (2H, m); 13C NMR (100 MHz, CDCl3) δ = 55.3
(2C), 55.6 (2C), 104.0 (2C), 113.0 (4C), 115.0 (2C), 124.4 (2C),
125.4 (2C), 130.4 (4C), 131.6 (2C), 134.3 (2C), 139.6 (2C), 148.5
(2C), 157.5 (2C), 159.6 (2C), 189.6; IR (KBr) 3855, 1604, 1475,
1249, 1056 cm−1; HRMS-EI: m/z [M+] calcd for C33H26O5S2
566.1222, found 566.1222.
Bis[2-(3-hydroxyphenyl)-6-methoxybenzo[b]thiophen-3-yl]-
methanone 2t. 77% Yield (83.1 mg), yellow powder, mp
295–296 °C; 1H NMR (400 MHz, DMSO-d6) δ = 3.83 (6H, s),
6.36–6.50 (6H, m), 6.66 (2H, t, J = 8.0 Hz), 7.11 (2H, dd, J = 2.4,
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