Pd(II)-catalyzed ligand controlled synthesis of pyrazole-4-carboxylates and benzo[b]thiophene-3-carboxylates

Article abstract of DOI:10.1039/c4ob01576b

Cyclization-carbonylation of α,β-alkynic hydrazones and (o-alkynylphenyl) (methoxymethyl) sulfides with Pd(tfa)₂ in DMSO/MeOH afforded methyl pyrazole-4-carboxylates and benzo[b]thiophene-3-carboxylates, respectively, in good yields. A simple change of the ligand (solvent) allowed controlled, effective switching between cyclization-carbonylation-cyclization-coupling (CCC-coupling) reactions and cyclization-carbonylation reactions.

Full text of DOI:10.1039/c4ob01576b

Volume 12 Number 43 21 November 2014 Pages 8564–8784
Organic &
Biomolecular
Chemistry
www.rsc.org/obc
ISSN 1477-0520
PAPER
Keisuke Kato et al.
Pd(II)-catalyzed ligand controlled synthesis of pyrazole-4-carboxylates and
benzo[b]thiophene-3-carboxylates

Organic &
Biomolecular Chemistry
View Article Online
View Journal | View Issue
PAPER
Pd(II)-catalyzed ligand controlled synthesis of
pyrazole-4-carboxylates and benzo[b]thiophene-
3-carboxylates†
Cite this: Org. Biomol. Chem., 2014,
12, 8619
Yogesh Daulat Dhage, Hiroki Daimon, Cheng Peng, Taichi Kusakabe,
Keisuke Takahashi, Yuichiro Kanno, Yoshio Inouye and Keisuke Kato*
Cyclization–carbonylation of α,β-alkynic hydrazones and (o-alkynylphenyl) (methoxymethyl) sulfides with
Pd(tfa)2 in DMSO/MeOH afforded methyl pyrazole-4-carboxylates and benzo[b]thiophene-3-carboxy-
lates, respectively, in good yields. A simple change of the ligand (solvent) allowed controlled, effective
switching between cyclization–carbonylation–cyclization-coupling (CCC-coupling) reactions and cycli-
zation–carbonylation reactions.
Received 25th July 2014,
Accepted 26th August 2014
DOI: 10.1039/c4ob01576b
www.rsc.org/obc
Introduction
Pyrazoles and benzo[b]thiophenes are important classes of
N- and S-heterocycles in pharmaceutical science.1 They are
found in a variety of drugs, pesticides and biologically active
compounds, such as razaxaban (anticoagulant), zometapine
(antidepressant), celecoxib (anti-inflammatory), fomepizole
(an antidote for methanol poisoning), cyenopyrafen (acari-
cide), raloxifene (a selective estrogen receptor modulator used
for treatment of osteoporosis) and penthiopyrad (fungicide).2
Pyrazole-4-carboxylates also possess antitumor, antimicrobial
and analgesic activities.3 They can be synthesized by several
methods: (i) thermal cycloaddition of sydnones with acetylenic
esters,4a (ii) 1,3-dipolar cycloaddition of nitrile imines,3a (iii)
condensation of β-enaminoketoesters or cyano ketene dithio-
acetals with hydrazines4b,c and (iv) Vilsmeier cyclization of
hydrazones.4d Although α,β-alkynic hydrazones are good pre-
cursors for the synthesis of pyrazoles,5 there is only one
example of cyclization–carbonylation reaction of α,β-alkynic
hydrazones (Scheme 1, condition B).6a Recently, we reported
that the cyclization–carbonylation–cyclization-coupling reac-
tion (CCC-coupling reaction) of α,β-alkynic hydrazones 1 and
(o-alkynylphenyl) (methoxymethyl) sulfides 4 catalyzed by pal-
ladium(II)-bisoxazoline (box) complexes afforded bis(pyrazol-3-
yl)methanones 2 and bis(benzothiophen-3-yl)methanones 5,
Scheme 1 CCC-coupling (previous work)6a versus cyclization–
carbonylation (this work).
Schemes 1 and 2), dimeric ketones 2a and 5a were obtained in
47–49% yields along with low yields of pyrazole-4-carboxylate
3a (38%) and benzo[b]thiophene 7a (11%). In the case of con-
dition B in Scheme 2, benzo[b]thiophene-3-carboxylate 6a was
not obtained. The course of the reaction can be switched by a
simple change of the ligand (or the solvent) to afford pyrazole-
4-carboxylate 3a and benzo[b]thiophene-3-carboxylate 6a selec-
tively. Very recently, we reported6c palladium(II)-catalyzed
ligand controlled synthesis of indole-3-carboxylates 10 and bis-
(indol-3-yl)methanones 9; the box complex gave bis(indol-3-yl)-
methanone 9a in good yield (condition A in Scheme 3). In the
absence of a ligand (condition B in Scheme 3), indole-3-car-
respectively, in good yields (condition
A in Schemes 1
and 2).6a,b In the absence of a box ligand (condition B in
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
and characterization data. See DOI: 10.1039/c4ob01576b
Scheme 2 CCC-coupling (previous work)6b versus cyclization–
carbonylation (this work).
This journal is © The Royal Society of Chemistry 2014
Org. Biomol. Chem., 2014, 12, 8619–8626 | 8619

View Article Online
Paper
Organic & Biomolecular Chemistry
Pd(PPh3)4 was ineffective, affording 3a in low yield (Table 1,
entry 4). The use of PdCl2(CH3CN)2 afforded 2a as the sole
product in increased yield (Table 1, entry 5). Next, we investi-
gated the reaction in mixed solvents containing MeOH accord-
ing to our previous findings.6c Although DMF–MeOH, THF–
MeOH and toluene–MeOH were not suitable as solvents, the
use of DMSO strikingly changed the course of the reaction,
affording pyrazole-4-carboxylate 3a as the major product
(Table 1, entries 6–12). A large amount of DMSO (DMSO–
MeOH = 5/1) led to decreased product yield, and the use of a
small amount of DMSO (DMSO–MeOH = 1/5) gave almost the
same result as that of entry 1 (Table 1, entries 10 and 11).
Eventually, the best result was obtained using a 2.5/3 ratio of
DMSO–MeOH, affording 3a in 91% yield (Table 1, entry 12). In
addition, PdCl2 and Pd(OAc)2 were not suitable catalysts
(Table 1, entries 13 and 14), and the use of CuCl2 instead of
p-benzoquinone afforded 2a in 30% yield along with recovery
of substrate 1a (34%).
Scheme 3 Previous work.6c
boxylate was obtained in 41% yield. Addition of DMSO (mixed
solvent; DMSO–MeOH) improved the yield of indole-3-carboxy-
lates. To investigate the generality of the effect of DMSO, we re-
examined the Pd(II)-catalyzed carbonylation of α,β-alkynic
hydrazones 1 and (o-alkynylphenyl) (methoxymethyl) sulfides
4 using mixed solvents. Consequently, we would like to report
here a new method for the synthesis of pyrazole-4-carboxylate
3 and benzo[b]thiophene-3-carboxylates 6 (condition C in
Schemes 1 and 2).
Having elucidated the optimum conditions for the reaction,
we then employed several α,β-alkynic hydrazone derivatives in
the cyclization–carbonylation reaction (Table 2). First, the reac-
tion of substrates derived from α,β-alkynic aldehydes and
Results and discussion
Initially, we selected 1a as a standard substrate to search for PhNHNH2 (R1 = H, Ar = Ph) was investigated (Table 2, entries
potential catalysts and solvents (Table 1). The results of entries 1–7). The substrates 1b–1d, bearing electron-donating substitu-
1–5 in Table 1 have been reported previously.6a The reaction of ents (R2 = 4-MePh, 4-MeOPh) and a thiophene ring, gave good
1a with Pd(tfa)2 (5 mol%) and p-benzoquinone (1.5 equiv.) in results which were similar to that of the parent substrate 1a
methanol under a carbon monoxide atmosphere (balloon) gen- (Table 2, entries 1–4). Replacement of the aryl groups at the
erated the bis(pyrazolyl)ketone 2a in 47% yield along with alkyne terminus with an alkyl group afforded a slightly lower
38% yield of pyrazole-4-carboxylate 3a (Table 1, entry 1). These yield (76%) of 3e (Table 2, entry 5). Both a Br substituent on
products were easily separated by silica gel chromatography. the Ar moiety (Ar = 4-BrPh) and an electron-withdrawing group
The use of [PdCl2(PPh3)2] and a (2,2′-bipyridine)dichloro-palla- (R2 = 4-CF3Ph) were tolerated (Table 2, entries 6 and 7). Next,
dium(II) complex also gave a mixture of the two products in the reactions of substrates derived from α,β-alkynic ketones
low yields (Table 1, entries 2 and 3). The palladium(0) complex (R1 = alkyl) and ArNHNH2 were investigated (Table 2, entries
Table 1 Optimization of the reactiona (synthesis of 3a)
Yield of
2a (%)
Yield of
3a (%)
Entry
Catalyst
Solvent
Time (h)
1
2
3
4
5
6
7
8
Pd(tfa)2
MeOH
MeOH
MeOH
MeOH
46
24
24
24
21
24
24
24
73
49
49
72
72
72
47
28
36
—
76
15
18
22
5
41
32
Trace
12
—
38
31
6
[PdCl2(PPh2)2]
[PdCl2(2,2′-bipy)]
Pd(PPh3)4
[PdCl2(CH3CN)2]
Pd(tfa)2
Pd(tfa)2
Pd(tfa)2
Pd(tfa)2
Pd(tfa)2
Pd(tfa)2
Pd(tfa)2
19
—
28
37
22
79
54
3
MeOH
DMF–MeOH (1/1)
THF–MeOH (1/1)
Toluene–MeOH (1/1)
DMSO–MeOH (1/1)
DMSO–MeOH (1/5)
DMSO–MeOH (5/1)
DMSO–MeOH (2.5/3)
DMSO–MeOH (2.5/3)
DMSO–MeOH (2.5/3)
9b
10b
11b
12b
13c
14d
91
—
—
PdCl2
Pd(OAc)2
a The results of entries 1–5 have been reported in ref. 6a. b 0 °C. c Recovery 34%. d Recovery 99%.
8620 | Org. Biomol. Chem., 2014, 12, 8619–8626
This journal is © The Royal Society of Chemistry 2014

View Article Online
Organic & Biomolecular Chemistry
Paper
Table 2 Synthesis of pyrazole-4-carboxylates
3
via cyclization–
Table 3 Optimization of the reactiona (Synthesis of 6a)
carbonylation
Temp (°C) Yield of Yield of Yield of
Temp (°C)
Time (h)
Yield of
3 (%)
Entry Solvent
Time (h)
5a (%)
6a (%)
7a (%)
Entry
R1
R2
Ar
1a
MeOH
−20 to
−10, 45
rt, 24
49
—
11
1
2
3
4
5
6
7
8
H
H
H
H
H
H
H
Me
Ph
Ph
Ph
Ph
Ph
0 °C, 71 h
0 °C, 72 h
0 °C, 24 h
0 °C, 21 h
0 °C, 72 h
40 °C, 22 h
40 °C, 72 h
−10 °C, 23 h
0 °C, 20 h
0 °C, 24 h
0 °C, 17 h
0 °C, 17 h
0 °C, 18 h
0 °C, 6 h
3a: 91
3b: 82
3c: 80
3d: 82
3e: 76
3f: 86
3g: 85
3h: 81
3i: 83
3j: 87
3k: 98
3l: 90
3m: 90
3n: 93
3o: 93
4-MePh
4-MeOPh
3-Thienyl
Octyl
Ph
Ph
Ph
2
DMF–MeOH (2/1)
2
1
9
45
13
65
21
8
8
9
71
76
—
—
—
—
—
—
3
4
5
CH2Cl2–MeOH (2/1) rt, 24
DMSO–MeOH (2/1) rt, 24
DMSO–MeOH (1/1) 5, 28
DMSO–MeOH (5/1) rt, 16
DMSO–MeOH (5/1) rt, 48
DMSO–MeOH (5/1) rt, 22
DMSO–MeOH (7/1) 5, 17
74
37
76
26
56
80
Ph
4-BrPh
4-CF3Ph
Ph
6
7b
8c
9
9
Phenethyl
Me
Me
Me
Phenethyl
i-Pr
Ph
Ph
Ph
Ph
n-Hexyl
n-Butyl
TMS
Ph
10
11
12
13
14
15
4-BrPh
4-CF3Ph
4-NO2Ph
Ph
Ph
Ph
a The result was reported in ref. 6b. b PdCl2 was employed. c Pd(NO3)2
was employed.
Me
0 °C, 47 h
Table 4 Synthesis of benzo[b]thiophene-3-carboxylate 6 via cycliza-
tion–carbonylation
8–15). For substrates 1h–l, bearing a Ph group at the alkyne ter-
minus, the reaction proceeded well (Table 2, entries 8–12). A
Br substituent on an Ar moiety (Ar = 4-BrPh) was also tolerated
(Table 2, entry 10). The substrates 1k and 1l, bearing electron-
withdrawing groups on the Ar moiety (Ar = 4-CF3Ph, 4-NO2Ph),
were transformed in 98% and 90% yields, respectively
(Table 2, entries 11 and 12). Replacement of the Ph group at
the alkyne terminus with alkyl groups also led to the desired
3m and 3n in good yields (Table 2, entries 13 and 14). It is
noteworthy that the presence of a TMS group at the alkyne ter-
minus was tolerated under the reaction conditions (Table 2,
entry 15).
Next, we re-investigated the carbonylation of (o-alkynyl-
phenyl) (methoxymethyl) sulfides 4a using mixed solvents
(Table 3). As reported recently, the reaction in MeOH without
ligands afforded bis(benzothiophen-3-yl)methanone 5a in 49%
yield along with the cyclized product 7a, while the ester
product 6a was not detected (Table 3, entry 1).6b When the
reaction was performed in a mixed-solvent, e.g., DMF–MeOH
(2/1) and CH2Cl2–MeOH (2/1), 7a was obtained as the major
product (Table 3, entries 2 and 3). As in the case of Tables 1
and 2, the use of DMSO strikingly changed the course of the
reaction, affording benzo[b]thiophene-3-carboxylate 6a as the
major product (Table 3, entry 4). Although an increased
amount of MeOH led to decreased product selectivity, the best
result was obtained in DMSO–MeOH (7/1) (Table 3, entries 5, 6
and 9). PdCl2 and Pd(NO3)2 were not suitable for this reaction
(Table 3, entries 7 and 8). Having elucidated the optimum con-
ditions for the reaction, we then employed a variety of (o-alkynyl-
Temp (°C)
Time (h)
Entry
R1
R2
Yield %
1
2
3
4
5
6
7a
8
Ph
H
H
H
H
H
H
MeO
H
5, 17
5, 48
5, 18
5, 17
0, 48
5, 96
−20, 24
0, 48
6a: 80
6b: 81
6c: 83
6d: 82
6e: 82
6f: 86
6g: 80
6h: 82
4-BrPh
4-ClPh
4-FPh
4-MePh
TMS
Ph
Phenethyl
a DMSO–MeOH (2/1).
conditions: 6b–e were obtained in similar yields as that of the
parent substrate 4a (Table 4, entries 2–5). Replacement of the
aryl groups at the alkyne terminus with a TMS group and an
alkyl group also led to the desired 6f and 6h, respectively, in
good yields (Table 4, entries 6 and 8). For substrate 4g, bearing
a methoxy group on an aromatic moiety, the reaction pro-
ceeded well (Table 4, entry 7).
A plausible mechanism for the reaction of 1a and 4a is
shown in Scheme 4. Nucleophilic attack by the nitrogen atom
of 1a at the electrophilically activated triple bond produces the
pyrazol-3-yl palladium intermediate A. In the case of 4a, a
similar intermediate A′ is produced, accompanied by removal
of the methoxymethyl group.8 Insertion of carbon monoxide
into intermediates A and A′ leads to acyl palladium intermedi-
ates B and B′, while protonolysis of intermediate A′ generates
7a. As reported previously, we believe that the box ligand
phenyl) (methoxymethyl) sulfides
4 in the cyclization–
carbonylation reaction (Table 4). The substrates 1b–e, bearing
three kinds of halogen substituents (F, Cl, Br) and a methyl
group on the phenyl ring, were tolerated under the reaction
This journal is © The Royal Society of Chemistry 2014
Org. Biomol. Chem., 2014, 12, 8619–8626 | 8621

View Article Online
Paper
Organic & Biomolecular Chemistry
tion pathway. An effective switching between cyclization–
carbonylation and cyclization–carbonylation–cyclization-coup-
ling (CCC-coupling) reactions was achieved. At the same time
a new method for the synthesis of pyrazole-4-carboxylates 3
and benzo[b]thiophene-3-carboxylates 6 was developed. These
reactions were general for a wide range of substrates. We are
currently investigating additional reactions based on this
DMSO–MeOH strategy for cyclization–carbonylation in the syn-
thesis of other types of heterocycles–carboxylates.
Experimental section
General information
All melting points were determined on a microscopic melting
point apparatus and are uncorrected. 1H NMR and 13C NMR
spectra were recorded on a 400 MHz (1H NMR) and 100 MHz
(13C NMR) spectrometer using CDCl3 as the solvent and TMS
as the internal standard. Coupling constants (J) are reported
in hertz (Hz), and spin multiplicities are presented by the fol-
lowing symbols: s (singlet), br-s (broad singlet), d (doublet),
br-d (broad doublet), t (triplet), q (quartet), and m (multiplet).
High-resolution mass spectra were obtained using high-resolu-
tion EI or ESI-TOF mass spectrometers. Infrared spectra (IR)
were recorded on a FT-IR spectrophotometer and are reported
as wavelength numbers (cm−1). All evaporations were per-
formed under reduced pressure. For column chromatography,
silica gel (63–200 mm) was employed. See ESI† for 1H NMR
and 13C NMR spectra of all new compounds.
Scheme 4 A plausible mechanism for the cyclization–carbonylation
reaction 1a and 4a.
enhances the π-electrophilicity of palladium(II),7 and thus pro-
motes coordination of the second triple bond to the acyl palla-
dium intermediates (C and C′), leading to a dimerization
reaction. On the other hand, methanolysis of the acyl palla-
dium intermediates B and B′ gave the ester products 3a and 6a
as a result of cyclization–carbonylation. Under condition C
(Schemes 1–3), DMSO acts as a neutral ligand instead of the
box (condition A) or MeOH (condition B),6c and it plays impor-
tant roles in the production of esters 3a and 6a, namely, (1)
stabilizing intermediates A and A′ to prevent protonolysis, sup-
pressing the formation of 7a; (2) facilitating the methanolysis
of the acyl palladium intermediates B and B′; and (3) impeding
coordination of the second triple bond to the acyl palladium
intermediates B and B′, suppressing the formation of dimeric
ketones 2a and 5a. Consequently, the ester products 3a and 6a
should be produced smoothly in the presence of DMSO as a
mixed solvent.
Preparation of substrates 1 and 4
The α,β-alkynic hydrazones 1 were prepared by condensation
of the corresponding α,β-alkynic aldehydes or ketones with
ArNHNH2 according to known literature procedures.5c,d,6a The
(o-alkynylphenyl) (methoxymethyl) sulfides 4 were prepared
from known o-iodoanilines by the published procedure.6b All
substrates were known compounds except 1k and 4f.
(Z)-1-(4-Nitrophenyl)-2-(4-phenylbut-3-yn-2-ylidene)-hydrazine
1
(1l). Yellow solid; mp 137–138 °C; H NMR (CDCl3): δ = 2.82
(3H, s), 7.08–7.12 (2H, m), 7.40–7.48 (3H, m), 7.54–7.57 (2H,
m), 8.15–8.18 (2H, m), 8.63 (1H, s); 13C NMR (CDCl3): δ = 22.4,
79.9, 102.4, 112.0, 120.7, 126.1, 128.6, 128.7, 130.0, 131.9,
140.5, 148.8; IR (KBr): 3306, 2173, 1596, 1499, 1478, 1330,
1272, 1144, 1114, 835, 752, 688 cm−1; HRMS-EI: m/z [M+] calcd
for C16H13N3O2: 279.1008; found: 279.1008.
Methoxymethyl 2-(trimethylsilylethynyl)phenyl sulfide (4f).
1
Brown oil; H NMR (CDCl3): δ = 0.27 (9H, s), 3.43 (3H, s), 5.04
(2H, s), 7.10–7.14 (1H, m), 7.23–7.27 (1H, m), 7.43 (1H, br-d,
J = 8.0 Hz), 7.56 (1H, br-d, J = 8.0 Hz); 13C NMR (CDCl3): δ =
Conclusions
In conclusion, we investigated the carbonylation reactions of 0.07 (3C), 56.2, 76.3, 100.6, 102.6, 123.2, 125.8, 128.4, 129.1,
α,β-alkynic hydrazones 1 and (o-alkynylphenyl) (methoxy- 132.9, 139.4; IR (KBr): 2945, 1697, 1681, 1456, 1354, 1225,
methyl) sulfides 4 with Pd(tfa)2 in a mixed solvent, and found 1010, 822, 755 cm−1; HRMS-EI: m/z [M+] calcd for C13H18O2SSi:
that DMSO–MeOH was very effective for controlling the reac- 250.0848; found: 250.0859.
8622 | Org. Biomol. Chem., 2014, 12, 8619–8626
This journal is © The Royal Society of Chemistry 2014

View Article Online
Organic & Biomolecular Chemistry
Paper
General procedure for the cyclization–carbonylation reaction
of α,β-alkynic hydrazones 1
978, 772, 696 cm−1; HRMS-EI: m/z calcd for C19H26N2O2 [M+]:
314.1994; found: 314.1995.
Methyl
1-(4-bromophenyl)-5-phenyl-1H-pyrazole-4-carb-
A 30 mL two-necked round-bottom flask containing a mag- oxylate (3f). Pale yellow solid; mp 112–113 °C; 1H NMR
netic stirring bar, substrate 1 (0.5 mmol), p-benzoquinone (CDCl3): δ = 3.75 (3H, s), 7.05–7.09 (2H, m), 7.26–7.28 (2H, m),
(81.1 mg, 0.75 mmol), DMSO (2 mL) and MeOH (6 mL) was 7.34–7.42 (5H, m), 8.17 (1H, s); 13C NMR (CDCl3): δ = 51.3,
fitted with a rubber septum and a three-way stopcock con- 113.8, 121.7, 126.6, 128.2, 128.4, 129.4, 130.3, 132.0, 138.2,
nected to a balloon filled with carbon monoxide. The appar- 142.6, 145.5, 163.1; IR (KBr): 3056, 1722, 1551, 1498, 1291,
atus was purged with carbon monoxide by pump-filling via 1223, 1130, 1068, 1014, 770, 697 cm−1; HRMS-EI: m/z calcd for
the three-way stopcock. A DMSO (1 mL) solution of Pd(tfa)2 C17H13BrN2O2 [M+]: 356.0160; found: 356.0156.
(8.3 mg, 0.025 mmol) was added to the stirred solution via a
Methyl 5-phenyl-1-((4-trifluoromethyl)phenyl)-1H-pyrazole-4-
syringe at the appropriate temperature. The remaining carboxylate (3g). Pale yellow solid; mp 100–101 °C; 1H NMR
catalyst was washed in DMSO (1 mL) twice, and stirred for a (CDCl3): δ = 3.75 (3H, s), 7.20–7.40 (7H, m), 7.48–7.55 (2H, m),
set period of time. The reaction mixture was diluted 8.20 (1H, s); 13C NMR (CDCl3): δ = 51.4, 114.2, 123.6 (q, JC–F
=
with CH2Cl2 (60 mL), water (40 mL) and 5% NaOH (10 mL). 270.8 Hz), 125.1, 126.0 (q, JC–F = 2.9 Hz), 128.3, 128.4, 129.6,
The layers were separated, and the aqueous layer was 129.7 (q, JC–F = 32.4 Hz), 130.3, 141.9, 142.9, 145.7, 163.0; IR
extracted with CH2Cl2 (25 mL). The combined organic layers (KBr): 3056, 1727, 1612, 1553, 1448, 1386, 1324, 1226, 1123,
were dried over MgSO4 and concentrated in vacuo. The crude 1064, 846 cm−1; HRMS-EI: m/z calcd for C18H13F3N2O2 [M+]:
product was purified by column chromatography on silica gel. 346.0929; found: 346.0929.
The fraction eluted with hexane–EtOAc (25/1–10/1) afforded
Methyl 3-methyl-1,5-diphenyl-1H-pyrazole-4-carboxylate (3h).
pyrazole-4-carboxylate 3, and that eluted with hexane–EtOAc Colorless solid; mp 122–123 °C; 1H NMR (CDCl3): δ = 2.58 (3H,
(3/1–2/1) afforded a small amount of bis(pyrazol-3-yl)metha- s), 3.69 (3H, s), 7.15–7.17 (2H, m), 7.22–7.37 (8H, m); 13C NMR
nones 2.
(CDCl3): δ = 14.3, 51.0, 111.6, 125.3, 127.6, 127.9, 128.7, 128.9,
Bis(1,5-diphenyl-1H-pyrazol-4-yl)methanone (2a),6a methyl 129.7, 130.3, 139.1, 146.4, 151.7, 164.3; IR (KBr): 2946, 1712,
1,5-diphenyl-1H-pyrazole-4-carboxylate (3a)6a and methyl 1595, 1548, 1502, 1311, 1238, 1101, 1091, 793, 693 cm−1
;
1-phenyl-5-(p-tolyl)-1H-pyrazole-4-carboxylate (3b). Pale yellow HRMS-EI: m/z calcd for C18H16N2O2 [M+]: 292.1212; found:
1
solid; mp 116–117 °C; H NMR (CDCl3): δ = 2.35 (3H, s), 3.75 292.1212.
(3H, s), 7.12–7.31 (9H, m), 8.16 (1H, s); 13C NMR (CDCl3): δ =
Methyl 3-phenethyl-1,5-diphenyl-1H-pyrazole-4-carboxylate
21.4, 51.2, 113.2, 125.3, 125.5, 127.8, 128.8, 130.3, 139.2, 139.3, (3i). Pale yellow solid; mp 113–114 °C; 1H NMR (CDCl3): δ =
142.4, 145.7, 163.4; IR (KBr): 3035, 1718, 1563, 1504, 1445, 3.01–3.05 (2H, m), 3.20–3.24 (2H, m), 3.62 (3H, s), 7.08–7.28
1382, 1293, 1225, 1130, 773, 693 cm−1; HRMS-EI: m/z calcd for (15H, m); 13C NMR (CDCl3): δ = 30.6, 35.5, 51.0, 111.1, 125.3,
C18H16N2O2 [M+]: 292.1212; found: 292.1212.
Methyl
125.8, 127.6, 127.9, 128.3, 128.5, 128.7, 128.8, 129.7, 130.3,
5-(4-methoxyphenyl)-1-phenyl-1H-pyrazole-4-carb- 139.1, 142.4, 146.5, 154.8, 164.0; IR (KBr): 3025, 2941, 1698,
oxylate (3c). Colorless solid; mp 125–126 °C; 1H NMR (CDCl3): 1596, 1487, 1384, 1322, 1237, 1182, 1100 760, 696 cm−1
;
δ = 3.76 (3H, s), 3.80 (3H, s), 6.83–6.87 (2H, m), 7.19–7.30 (7H, HRMS-EI: m/z calcd for C25H22N2O2 [M+]: 382.1681; found:
m), 8.16 (1H, s); 13C NMR (CDCl3): δ = 51.2, 55.2, 113.0, 113.5, 382.1680.
120.6, 125.3, 127.8, 128.8, 131.8, 139.3, 142.4, 145.5, 160.2,
163.5; IR (KBr): 3054, 1717, 1506, 1447, 1226, 1130, 775 cm−1
HRMS-EI: m/z calcd for C18H16N2O3 [M+]: 308.1161; found: (CDCl3): δ = 2.57 (3H, s), 3.68 (3H, s), 7.02–7.05 (2H, m),
308.1159.
7.21–7.24 (2H, m), 7.32–7.40 (5H, m); 13C NMR (CDCl3): δ =
Methyl
1-(4-bromophenyl)-3-methyl-5-phenyl-1H-pyrazole-
;
4-carboxylate (3j). Pale yellow solid; mp 99–100 °C; 1H NMR
Methyl 1-phenyl-5-(thiophen-3-yl)-1H-pyrazole-4-carboxylate 14.3, 51.0, 112.0, 121.3, 126.5, 128.1, 129.1, 129.4, 130.3, 131.9,
1
(3d). Colorless solid; mp 97–98 °C; H NMR (CDCl3): δ = 3.79 138.1, 146.4, 152.0, 164.1; IR (KBr): 3060, 1711, 1547, 1497,
(3H, s), 6.96 (1H, dd, J = 5.2 Hz, J = 1.2 Hz), 7.22–7.27 (3H, m), 1430, 1321, 1246, 1182, 1100, 1010, 700 cm−1; HRMS-EI: m/z
7.32–7.35 (3H, m), 7.39 (1H, dd, J = 2.8 Hz, J = 1.2 Hz), 8.15 calcd for C18H15BrN2O2 [M+]: 370.0317; found: 370.319.
(1H, s); 13C NMR (CDCl3): δ = 51.3, 113.2, 125.0, 125.3, 127.9,
Methyl 3-methyl-5-phenyl-1-(4-(trifluoromethyl)phenyl)-1H-
128.0, 128.2, 128.9, 128.9, 139.3, 140.7, 142.5, 163.3; IR (KBr): pyrazol-4-carboxylate (3k). Pale yellow solid; mp 113–114 °C;
3100, 1719, 1594, 1496, 1277, 1230, 1129, 1037, 973, 762, 1H NMR (CDCl3): δ = 2.58 (3H, s), 3.69 (3H, s), 7.24–7.30 (4H,
690 cm−1; HRMS-EI: m/z calcd for C15H12N2O2S [M+]: 284.0619; m), 7.34–7.43 (3H, m), 7.49–7.52 (2H, m); 13C NMR (CDCl3):
found: 284.0621.
δ = 14.3, 51.1, 112.5, 122.3, 125.0, 125.9 (q, JC–F = 30.4 Hz),
Methyl 5-octyl-1-phenyl-1H-pyrazole-4-carboxylate (3e). Pale 128.2, 129.36, 130.3 (q, JC–F = 263.2 Hz), 130.2, 141.9, 146.6,
yellow oil; mp 99–100 °C; 1H NMR (CDCl3): δ = 0.85 (3H, s), 152.4, 164.0; IR (KBr): 2944, 1712, 1615, 1429, 1388, 1325,
1.17–1.27 (10H, m), 1.47–1.55 (2H, m), 2.90–2.94 (2H, m), 3.85 1240, 1103, 844, 760, 697 cm−1; HRMS-EI: m/z calcd for
(3H, s), 7.38–7.40 (2H, m), 7.46–7.52 (3H, m), 8.01 (1H, s); 13C C19H15F3N2O2 [M+]: 360.1086; found: 360.1086.
NMR (CDCl3): δ = 14.0, 22.5, 24.9, 28.9, 28.9, 29.0, 29.2, 31.7,
Methyl
3-methyl-1-(4-nitrophenyl)-5-phenyl-1H-pyrazol-4-
51.1, 111.8, 125.9, 128.8, 129.2, 139.0, 141.9, 148.5, 163.9; carboxylate (3l). Pale yellow solid; mp 127–128 °C; 1H NMR
IR (KBr): 2928, 2857, 1717, 1595, 1553, 1502, 1460, 1252, 1091, (CDCl3): δ = 2.59 (3H, s), 3.70 (3H, s), 7.24–7.27 (2H, m),
This journal is © The Royal Society of Chemistry 2014
Org. Biomol. Chem., 2014, 12, 8619–8626 | 8623

View Article Online
Paper
Organic & Biomolecular Chemistry
7.32–7.44 (5H, m), 8.09–8.13 (2H, m); 13C NMR (CDCl3): δ = 6d were obtained in 81–82% yields after recrystallization
14.3, 51.2, 113.2, 124.3, 124.9, 128.5, 129.2, 129.6, 130.1, 144.0, (hexane).
146.0, 146.8, 152.9, 163.8; IR (KBr): 2949, 1715, 1597, 1523, Bis(2-phenylbenzo[b]thiophen-3-yl)methanone (5a)6b
1505, 1321, 1249, 1105, 763, 700 cm−1; HRMS-EI: m/z calcd for Methyl 2-phenylbenzo[b]thiophen-3-carboxylate (6a)9
C18H15N3O4 [M+]: 337.1063; found: 337.1064.
Methyl
2-phenylbenzo[b]thiophene (7a)10
5-hexyl-3-phenethyl-1-phenyl-1H-pyrazole-4-carb- Methyl 2-(4-bromophenyl)benzo[b]thiophen-3-carboxylate (6b)
oxylate (3m). Pale yellow solid; mp 38 °C; 1H NMR (CDCl3): δ = Orange solid; mp 80–81 °C; H NMR (CDCl3): δ = 3.79 (3H, s),
0.84 (3H, t, J = 7.2 Hz), 1.14–1.28 (6H, m), 1.50–1.57 (2H, m), 7.37–7.43 (3H, m), 7.46–7.51 (1H, m), 7.55–7.59 (2H, m), 7.82
2.85–2.90 (2H, m), 3.0–3.04 (2H, m), 3.19–3.23 (2H, m), 3.88 (1H, br-d, J = 8.0 Hz), 8.36 (1H, br-d, J = 8.0 Hz); 13C NMR
(3H, s), 7.18–7.22 (1H, m), 7.28–7.32 (4H, m), 7.35–7.39 (2H, (CDCl3): δ = 51.6, 121.7, 123.1, 123.3, 124.7, 125.1, 125.5,
m), 7.42–7.52 (3H, m); 13C NMR (CDCl3): δ = 13.9, 22.4, 25.5, 131.0, 131.3, 132.9, 138.3, 138.4, 150.4, 164.1; IR (KBr): 2945,
29.1, 29.1, 30.7, 31.1, 35.6, 50.9, 109.2, 125.8, 126.2, 128.2, 1697, 1681, 1456, 1354, 1225, 1010, 822, 755 cm−1; HRMS-EI:
128.5, 128.7, 129.2, 139.0, 142.2, 149.7, 154.5, 164.5; IR (KBr): m/z calcd for C16H11BrO2S [M+]: 345.9663; found: 345.9693.
1
2942, 2854, 1710, 1595, 1541, 1460, 1267, 1108, 758, 696 cm−1
HRMS-EI: m/z calcd for C25H30N2O2 [M+]: 390.2307; found: (6c). Orange solid; mp 64–65 °C; 1H NMR (CDCl3): δ = 3.79
;
Methyl
2-(4-chlorophenyl)benzo[b]thiophen-3-carboxylate
390.2308.
Methyl
(3H, s), 7.39–7.51 (6H, m), 7.82 (1H, br-d, J = 8.0 Hz), 8.38 (1H,
5-butyl-3-isopropyl-1-phenyl-1H-pyrazole-4-carb- br-d, J = 8.0 Hz); 13C NMR (CDCl3): δ = 51.6, 121.7, 123.1,
1
oxylate (3n). Pale yellow solid; mp 45–46 °C; H NMR (CDCl3): 124.7, 125.1, 125.5, 128.3, 130.7, 132.4, 135.0, 138.3, 138.4,
δ = 0.81 (3H, t, J = 7.2 Hz), 1.20–1.31 (2H, m), 1.32 (6H, d, J = 150.4, 164.1; IR (KBr): 2946, 1698, 1429, 1355, 1224, 1091,
6.8 Hz), 1.46–1.54 (2H, m), 2.88–2.86 (2H, m), 3.52–3.62 (1H, 1018, 824, 768 cm−1; HRMS-EI: m/z calcd for C16H11ClO2S
m), 3.85 (3H, s), 7.36–7.49 (5H, m); 13C NMR (CDCl3): δ = 13.5, [M+]: 302.0168; found: 302.0169.
21.9 (2C), 22.5, 25.4, 27.2, 31.4, 50.8, 108.5, 126.2, 128.6, 129.1,
Methyl
2-(4-fluorophenyl)benzo[b]thiophen-3-carboxylate
139.2, 149.3, 160.4, 164.8; IR (KBr): 2967, 2870, 1698, 1539, (6d). Orange solid; mp 78–80 °C; 1H NMR (CDCl3): δ = 3.79
1448, 1281, 1174, 1106, 795, 697 cm−1; HRMS-EI: m/z calcd for (3H, s), 7.46–7.52 (3H, m), 7.38–7.42 (1H, m), 7.14–7.16 (2H,
C18H24N2O2 [M+]: 300.1836; found: 300.1838.
m), 8.35 (1H, br-d, J = 8.4 Hz), 7.82 (1H, br-d, J = 8.0 Hz); 13C
Methyl 3-methyl-1-phenyl-5-trimethylsilyl-1H-pyrazole-4-car- NMR (CDCl3): δ = 51.6, 115.2 (d, JC–F = 21.9 Hz), 121.7, 123.0,
1
boxylate (3o). Colorless solid; mp 63–64 °C; H NMR (CDCl3): 124.7, 125.1, 125.5, 129.9 (d, JC–F = 3.8 H), 131.2 (d, JC–F
δ = 0.05 (9H, s), 2.49 (3H, s), 3.85 (3H, s), 7.32–7.37 (2H, m), 8.6 Hz), 138.3, 138.4, 150.8, 163.1 (d, JC–F = 248 Hz), 164.2;
7.42–7.45 (3H, m); 13C NMR (CDCl3): δ = 0.0 (3C), 13.7, 51.2, IR (KBr): 2924, 1715, 1701, 1457, 1203, 1159, 750 cm−1
121.1, 127.1, 129.1, 129.3, 142.3, 149.3, 151.5, 165.5; IR (KBr): HRMS-EI: m/z calcd for C16H11FO2S [M+]: 286.0464; found:
=
;
2996, 1705, 1596, 1501, 1261, 1110, 1008, 848, 774, 699 cm−1
;
286.0466.
HRMS-EI: m/z calcd for C15H20N2O2Si [M+]: 288.1294; found:
Methyl 2-(4-methylphenyl)benzo[b]thiophen-3-carboxylate
(6e). Yellow oil; 1H NMR (CDCl3): δ = 2.40 (3H, s), 3.77 (3H, s),
7.22–7.24 (2H, m), 7.34–7.47 (4H, m), 7.79 (1H, br-d, J =
8.4 Hz), 8.31 (1H, br-d, J = 8.0 Hz); 13C NMR (CDCl3): δ = 21.3,
51.5, 121.6, 122.5, 124.4, 124.8, 125.3, 128.9, 129.2, 130.9,
288.1292.
General procedure for the cyclization–carbonylation reaction
of (o-alkynylphenyl) (methoxymethyl) sulfides 4
A 30 mL two-necked round-bottom flask containing a mag- 138.4, 138.5, 138.9, 152.1, 164.5; IR (KBr): 2944, 1497, 1350,
netic stirring bar, substrate 1 (0.4 mmol), p-benzoquinone 1159, 1019, 818, 740 cm−1; HRMS-EI: m/z calcd for C17H14O2S
(65 mg, 0.6 mmol) and mixed solvent (5 mL) was fitted with a [M+]: 282.0715; found: 282.0714.
rubber septum and a three-way stopcock connected to a
Methyl 2-(4-trimethylsilyl)phenylbenzo[b]thiophen-3-carbox-
balloon filled with carbon monoxide. The apparatus was ylate (6f). Yellow oil; 1H NMR (CDCl3): δ = 0.44 (9H, s), 3.98
purged with carbon monoxide by pump-filling via the three- (3H, s), 7.35–7.39 (1H, m), 7.43–7.47 (1H, m), 7.86 (1H, br-d,
way stopcock. A mixed solvent (1 mL) solution of Pd(tfa)2 J = 8.4 Hz), 8.54 (1H, br-d, J = 8.4 Hz); 13C NMR (CDCl3): δ =
(6.7 mg, 0.02 mmol) was added to the stirred solution via a 0.18 (3C), 51.5, 121.9, 124.8, 124.8, 125.3, 132.5, 139.6, 142.8,
syringe at the appropriate temperature. The remaining catalyst 154.6, 164.5; IR (KBr): 2946, 1693, 1414, 1262, 1186, 1045, 965,
was washed in the mixed solvent (1 mL) twice, and stirred for 762 cm−1; HRMS-EI: m/z calcd for C13H16O2SSi [M+]: 264.0640;
a set period of time. The reaction mixture was diluted with found: 264.0641.
CH2Cl2 (60 mL), water (40 mL) and 5% NaOH (10 mL). The
Methyl 5-methoxy-2-phenylbenzo[b]thiophen-3-carboxylate
1
layers were separated, and the aqueous layer was extracted (6g). White solid; mp 100–110 °C; H NMR (CDCl3): δ = 3.76
with CH2Cl2 (25 mL). The combined organic layers were dried (3H, s), 3.89 (3H, s), 7.08 (1H, dd, J = 8.8 Hz, J = 2.4 Hz), 7.27
over MgSO4 and concentrated in vacuo. The crude product was (1H, d, J = 2.4 Hz), 7.40–7.46 (3H, m), 7.47–7.52 (2H, m), 8.23
purified by column chromatography on silica gel. The fraction (1H, br-d, J = 9.2 Hz); 13C NMR (CDCl3): δ = 51.5, 55.5, 104.0,
eluted with hexane–Et2O (200/1) afforded benzo[b]thiophene-3- 115.3, 122.3, 125.3, 128.1, 128.6, 129.4, 132.4, 134.0, 139.9,
carboxylate 6 and a small amount of bis(benzothiophen-3-yl) 149.3, 157.6, 164.4; IR (KBr): 2943, 1701, 1435, 1205, 1065, 827,
methanone 5. In the case of entries 2 and 4 in Table 4, a small 769 cm−1; HRMS-EI: m/z calcd for C17H14O3S [M+]: 298.0664;
amount of ketone 5 contaminated ester 6. Pure esters 6b and found: 298.0663.
8624 | Org. Biomol. Chem., 2014, 12, 8619–8626
This journal is © The Royal Society of Chemistry 2014

View Article Online
Organic & Biomolecular Chemistry
Paper
Methyl 2-phenethylbenzo[b]thiophen-3-carboxylate (6h).
Yellow oil; H NMR (CDCl3): δ = 3.03–3.07 (2H, m), 3.53–3.57
T. B. Brenneman, R. C. Kemerait Jr. and G. G. Hammes,
Pestic. Manag. Sci., 2009, 65, 66; (h) I. Jarak, M. Kralj,
L. Suman, G. Pavlovic, J. Dogan, I. Piantanida, M. Zinic,
K. Pavelic and G. Karminski-Zamola, J. Med. Chem., 2005,
48, 2346; (i) N. J. Hrib, J. G. Jurcak, D. E. Bregna,
R. W. Dunn, H. M. Geyer, H. B. Hartman, J. R. Roehr,
K. L. Rogers, D. K. Rush, A. M. zczepanik, M. R. Szewczak,
C. A. Wilmot and P. G. Conway, J. Med. Chem., 1992, 35,
2712; ( j) D. H. Boschelli, J. B. Kramer, S. S. Khatana,
R. J. Sorenson, D. T. Connor, M. A. Ferin, C. D. Wright,
M. E. Lesch, K. Imre, G. C. Okonkwo, D. J. Schrier,
M. C. Conroy, E. Ferguson, J. Woelle and U. Saxena, J. Med.
Chem., 1995, 38, 4597; (k) D. H. Boschelli, J. B. Kramer,
S. S. Khatana, R. J. Sorenson, D. T. Connor, M. A. Ferin,
C. D. Wright, M. E. Lesch, K. Imre, G. C. Okonkwo,
D. J. Schrier, M. C. Conroy, E. Ferguson, J. Woelle and
1
(2H, m), 3.94 (3H, s), 7.18–7.33 (6H, m), 7.38–7.43 (1H, m),
7.72 (1H, br-d, J = 8.4 Hz), 8.39 (1H, br-d, J = 8.4 Hz); 13C NMR
(CDCl3): δ = 32.7, 37.5, 51.4, 121.7, 122.2, 124.4, 124.5, 125.1,
126.2, 128.4, 128.5, 137.1, 138.3, 140.7, 156.7, 164; IR (KBr):
2940, 1497, 1275, 1236, 1180, 759 cm−1; HRMS-EI: m/z calcd
for C18H16O2S [M+]: 296.0871; found: 296.0871.
Acknowledgements
This work was supported by a JSPS KAKENHI grant (no.
24590026).
U.
Saxena,
J.
Med.
Chem.,
1992,
35,
958;
References
(l) M.-J. R. P. Queiroz, I. C. F. R. Ferreira, Y. D. Gaetano,
G. Kirsch, R. C. Calhelha and L. M. Estevinho, Bioorg. Med.
Chem., 2006, 14, 6827; (m) K. G. Pinney, A. D. Bounds,
K. M. Dingeman, V. P. Mocharla, G. R. Pettit, R. Bai and
E. Hamel, Bioorg. Med. Chem. Lett., 1999, 9, 1081.
3 (a) H. Sekkak, E. M. Rakib, M.-A. Abdelouahid, A. Hafid
and A. E. Malki, Int. J. Org. Chem., 2013, 3, 37;
(b) A. S. Shawali, T. A. Farghaly and A. R. Al-Dahshoury,
ARKIVOC, 2009, 14, 88; (c) B. Chandrakantha,
A. M. Isloor, P. Shetty, S. Isloor, S. Malladi and
H. K. Fun, Med. Chem. Res., 2012, 21, 2702;
(d) R. Sridhar, P. T. Perumal, S. Etti, G. Shanmugam,
1 (a) H. H. Seltzman, Drug Dev. Res., 2009, 70, 601;
(b) I. I. Gerus, R. X. Mironetz, I. S. Kondratov,
A. V. Bezdudny, Y. V. Dmytriv, O. V. Shishkin, V. S. Starova,
O. A. Zaporozhets, A. A. Tolmachev and P. K. Mykhailiuk,
J. Org. Chem., 2012, 77, 47; (c) C. Wasylyk, H. Zheng,
C. Castell, L. Debussche, M.-C. Multon and B. Wasylyk,
Cancer Res., 2008, 68, 1275; (d) S. Kiyonaka, K. Kato,
M. Nishida, K. Mio, T. Numaga, Y. Sawaguchi, T. Yoshida,
M. Wakamori, E. Mori, T. Numata, M. Ishii, H. Takemoto,
A. Ojida, K. Watanabe, A. Uemura, H. Kurose, T. Morii,
T. Kobayashi, Y. Sato, C. Sato, I. Hamachi and Y. Mori, Proc.
Natl. Acad. Sci. U. S. A., 2009, 106, 5400; (e) C.-H. Cho,
B. Neuenswander, G. H. Lushington and R. C. Larock,
J. Comb. Chem., 2009, 11, 900; (f) C.-H. Cho,
B. Neuenswander and R. C. Larock, J. Comb. Chem., 2010,
12, 278; (g) L. Berrade, B. Aisa, M. J. Ramirez, S. Galiano,
S. Guccione, L. R. Moltzau, F. O. Levy, F. Nicoletti,
G. Battaglia, G. Molinaro, I. Aldana, A. Monge and S. Perez-
Silanes, J. Med. Chem., 2011, 54, 3086; (h) H. F. Guo,
H. Y. Shao, Z. Y. Yang, S. T. Xue, X. Li, Z. Y. Liu, X. B. He,
J. D. Jiang, Y. Q. Zhang, S. Y. Si and Z. R. Li, J. Med. Chem.,
2010, 53, 1819.
2 (a) T. D. Penning, J. J. Talley, S. R. Bertenshaw, J. S. Carter,
P. W. Collins, S. Docter, M. J. Graneto, L. F. Lee,
J. W. Malecha, J. M. Miyashiro, R. S. Rogers, D. J. Rogier,
S. S. Yu, G. D. Anderson, E. G. Burton, J. N. Cogburn,
S. A. Gregory, C. M. Koboldt, W. E. Perkins, K. Seibert,
A. W. Veenhuizen, Y. Y. Zhang and P. C. Isakson, J. Med.
Chem., 1997, 40, 1347; (b) S. R. Cox, S. Liao, M. Payne-
Johnson, R. J. Zielinski and M. R. Stegemann, J. Vet. Phar-
macol. Ther., 2011, 34, 1; (c) D. Zhang, N. Raghavan,
S.-Y. Chen, H. Zhang, M. Quan, L. Lecureux, L. M. Patrone,
P. Y. S. Lam, S. J. Bonacorsi, R. M. Knabb, G. L. Skiles and
K. He, Drug Metab. Dispos., 2008, 36, 303; (d) H. A. De
Wald, S. Lobbestael and B. P. H. Poschel, J. Med. Chem.,
1981, 24, 982; (e) M. J. Casavant, Pediatrics, 2001, 107, 170;
(f) H. Murakami, S. Masuzawa, S. Takii and T. Ito,
Patent, JP2003201280, 2003, p. 38; (g) A. K. Culbreath,
M.
N.
Ponnuswamy,
V.
R.
Prabavathyc
and
N. Mathivanan, Bioorg. Med. Chem. Lett., 2004, 14, 6035.
4 (a) H. Gotthardt and F. Reiter, Chem. Ber., 1979, 112, 1193;
(b) Y. O. Ko, Y. S. Chun, C.-L. Park, Y. Kim, H. Shin, S. Ahn,
J. Hong and S. Lee, Org. Biomol. Chem., 2009, 7, 1132;
(c) S. K. Abubukkar, S. D. Minhaj and K. G. Baheti, Asian
J. Chem., 2012, 24, 2947; (d) R. Sridhar and P. T. Perumal,
Synth. Commun., 2003, 33, 1483.
5 For recent examples, see: (a) Y. Suzuki, S. Naoe, S. Oishi,
N. Fujii and H. Ohno, Org. Lett., 2012, 14, 326; (b) J. Qian,
Y. Liu, J. Zhu, B. Jiang and Z. Xu, Org. Lett., 2011, 13, 4220;
(c) M. Zora and A. Kivrak, J. Org. Chem., 2011, 76, 9379;
(d) M. Zora, A. Kivrak and C. Yazici, J. Org. Chem., 2011, 76,
6726; (e) B. Willy and T. J. J. Müller, Org. Lett., 2011, 13,
2082; (f) J. P. Waldo, S. Mehta and R. C. Larock, J. Org.
Chem., 2008, 73, 6666; (g) M. S. M. Ahmed, K. Kobayashi
and A. Mori, Org. Lett., 2005, 7, 4487.
6 (a) T. Kusakabe, H. Sagae and K. Kato, Org. Biomol. Chem.,
2013, 11, 4943; (b) Y. Jiang, T. Kusakabe, K. Takahashi and
K. Kato, Org. Biomol. Chem., 2014, 12, 3380; (c) R. Shen,
T. Kusakabe, K. Takahashi and K. Kato, Org. Biomol. Chem.,
2014, 12, 4533.
7 (a) K. Kato, S. Motodate, T. Mochida, T. Kobayashi and
H. Akita, Angew. Chem., 2009, 121, 3376, (Angew. Chem. Int.
Ed., 2009, 48, 3326); (b) S. Motodate, T. Kobayashi, M. Fujii,
T. Mochida, T. Kusakabe, S. Katoh, H. Akita and K. Kato,
Chem. – Asian J., 2010, 5, 2221; (c) K. Kato, R. Teraguchi,
This journal is © The Royal Society of Chemistry 2014
Org. Biomol. Chem., 2014, 12, 8619–8626 | 8625

View Article Online
Paper
Organic & Biomolecular Chemistry
S. Yamamura, T. Mochida, H. Akita, T. A. Peganova,
8 The methoxymethyl group may be removed by acetal
exchange (or hydrolysis) after cyclization.
9 K. Liu, F. Jia, H. Xi, Y. Li, X. Zheng, Q. Guo, B. Shen and
Z. Li, Org. Lett., 2013, 15, 2026.
N. V. Vologdin and O. V. Gusev, Synlett, 2007, 638;
(d) K. Kato, R. Teraguchi, S. Motodate, A. Uchida,
T. Mochida, T. A. Peganova, N. V. Vologdin and H. Akita,
Chem. Commun., 2008, 3687.
10 A. B. Biro and A. Kotschy, Eur. J. Org. Chem., 2007, 1364.
8626 | Org. Biomol. Chem., 2014, 12, 8619–8626
This journal is © The Royal Society of Chemistry 2014