Efficient synthesis of benzothiophenes by [4+1] cycloaddition of 2-mercaptobenzaldehyde derivatives with isocyanides

Article abstract of DOI:10.1016/j.tet.2016.09.054

We developed a [4+1] cycloaddition reaction of isocyanides with 2-mercaptobenzaldehydes and/or their disulfide derivatives, promoted by LiI·2H₂O, to afford benzothiophene derivatives in moderate to good yields. Isocyanides, 2-mercaptobenzaldehydes and disulfide derivatives of various types were used successfully in the reaction.

Full text of DOI:10.1016/j.tet.2016.09.054

Accepted Manuscript
Efficient synthesis of benzothiophenes by [4+1] cycloaddition of 2-
mercaptobenzaldehyde derivatives with isocyanides
Takahiro Soeta, Saori Shitaya, Takumi Okuno, Shuhei Fujinami, Yutaka Ukaji
PII:
S0040-4020(16)30984-X
10.1016/j.tet.2016.09.054
TET 28125
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 25 August 2016
Revised Date: 21 September 2016
Accepted Date: 23 September 2016
Please cite this article as: Soeta T, Shitaya S, Okuno T, Fujinami S, Ukaji Y, Efficient synthesis of
benzothiophenes by [4+1] cycloaddition of 2-mercaptobenzaldehyde derivatives with isocyanides,
Tetrahedron (2016), doi: 10.1016/j.tet.2016.09.054.
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ACCEPTED MANUSCRIPT
O
O
R1-NC
H
O
R2
H
LiI•2H2O (1.0 equiv)
or
R2
S
S
R2
R2
N
dioxane, reflux
SH
H
R1
S
up to 97% yield
O

ACCEPTED MANUSCRIPT
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Efficient Synthesis of Benzothiophenes by [4+1] Cycloaddition of
2-Mercaptobenzaldehyde Derivatives with Isocyanides
Leave this area blank for abstract info.
Takahiro Soeta, Saori Shitaya, Takumi Okuno, Shuhei Fujinami, Yutaka Ukaji*
Division of Material Chemistry, Graduate School of Natural Science and Technology, Kanazawa University, Kakuma,
Kanazawa 920-1192, Japan

1
ACCEPTED MANUSCRIPT
Tetrahedron
journal homepage: www.elsevier.com
Efficient Synthesis of Benzothiophenes by [4+1] Cycloaddition of 2-
Mercaptobenzaldehyde Derivatives with Isocyanides
Takahiro Soeta*, Saori Shitaya, Takumi Okuno, Shuhei Fujinami, Yutaka Ukaji*
Division of Material Sciences, Graduate School of Natural Science and Technology, Kanazawa University, Kakuma, Kanazawa 920-1192, Japan
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
We developed a [4+1] cycloaddition reaction of isocyanides with 2-mercaptobenzaldehydes
and/or their disulfide derivatives, promoted by LiI·2H2O, to afford benzothiophene derivatives
in moderate to good yields. Isocyanides, 2-mercaptobenzaldehydes and disulfide derivatives of
various types were used successfully in the reaction.
Available online
2009 Elsevier Ltd. All rights reserved
.
Keywords:
Keyword_1
Keyword_2
Keyword_3
Keyword_4
Keyword_5
1. Introduction
Benzothiophene derivatives have been the subject of much
attention and are frequently found in pharmaceuticals.5 They are
also useful as building blocks in materials science.6 Owing to
these unique properties, various methods of synthesizing
benzothiophene derivatives have been investigated, and a number
of combinatorial techniques have recently been developed,
including one using Friedel-Crafts type aroylation,7 and an
electrophilic cyclization.8 These methods can only be used with a
limited number of substrates; however, benzothiophene
derivatives are not readily accessed through existing preparative
methods. To address this deficiency, we herein report [4+1]
cycloaddition of isocyanides to 2-mercaptobenzaldehyde
derivatives promoted by a lithium iodide to afford various
benzothiophene derivatives.
The Passerini reaction is one of the oldest multicomponent
reactions, and has been found to be useful in the construction of
multifunctional α-acyloxyamides.1 It is probably the best method
for producing α-acyloxyamide in a highly convergent manner,
and a large number of biologically active substances can be
accessed quickly in this way.2 The Passerini reaction generally
requires a carboxylic acid, which activates an aldehyde and traps
a
nitrilium cation to form an acyloxylated intermediate;
subsequent acyl transfer leads to the corresponding α-acyloxy
amides. The requirement for a carboxylic acid limits the
application of this reaction to the construction of a particular
range of molecules. To overcome this limitation, we reasoned
that a compound Z–X, composed of an electrophile Z and a
nucleophilic group X, could essentially perform the same
function as the carboxylic acid in the Passserini reaction. Based
on this hypothesis, we previously developed O-silylative, O-
phosphinative, and O-sulfinative Passerini reactions as well as
borinic acid-catalyzed α-addition of isocyanide (Scheme 1).3 In
addition, we expanded this concept to intramolecular trapping of
a nitrilium intermediate in an Ugi-type reaction. Thus, when a
molecule contains both an electrophile (such as C=N) and a
potential nucleophilic group (Nu–), intramolecular trapping of the
nitrilium intermediate should be readily achieved in a manner
similar to the intermolecular version of the reaction.4 Based on
these investigations, we focused on the utility of 2-
mercaptobenzaldehyde for effective synthesis of benzothiophene
derivatives (Scheme 2).
Scheme 1 O-Silylative Passerini reaction, O-phosphinative
Passerini reaction, O-sulfinative Passerini reaction, and
borinic-acid-catalyzed α-addition of an isocyanide.

2
Tetrahedron
benzothiophene derivatives 3ba–3da in moderate to good yields.
Scheme 2 Working hypothesis
ACCEPTED MANUSCRIPT
The structure of the product was confirmed by X-ray
crystallographic analysis of a single crystal of 3af. The structure
of 3af is shown in Figure 1.
Figure 1 X-ray structure of 3af
2. Results and Discussion
First, we examined whether 2-mercaptobenzaldehyde (1a) was
capable of participating in a Passerini-type reaction to afford the
corresponding benzothiophene derivatives. For this, we used a
combination of 2-mercaptobenzaldehyde (1a) and tert-octyl
isocyanide (2a, 3.0 equiv) in the presence of a catalytic amount
of phenylborinic acid, which has been shown to be useful in
catalyzing α-addition of isocyanide,3d in dichloroethane (DCE) at
80 °C. Once the starting material had been consumed after 18 h,
1
the reaction mixture was purified and characterized. H-NMR,
13C-NMR, IR and HRMS spectroscopies revealed that the
structure of the product was different from what was expected:
the hydroxy group had been oxidized during the reaction, giving
the benzothiophene-3(2H)-one derivative 3aa (eq 1).
Table 1 Results of Passerini-type [4+1] cycloaddition reaction
using 2-mercaptobenzaldehyde under various conditions.
Entry
1
Promoter
-
Solv.
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
toluene
DCE
Yield / %
62
Based on these results, we optimized the reaction conditions
(Table 1). When 2-mercaptobenzaldehyde (1a) was refluxed in
dioxane with tert-octyl isocyanide (2a) (1.5 equiv), the starting
material 1a was consumed after 1 h and the desired 3aa was
obtained in 62% yield (entry 1). Chlorotrimethylsilane (TMSCl)
2
TMSCl
Ph2BOH
LiI·2H2O
LiI
22
3
48
4
72
and diphenylborinic acid, which are useful Lewis acids for the
4d
isocyanide-based reactions,3d,
were not effective in this
5
41
reaction, affording the product in lower yields (entries 2 and 3).
LiI·2H2O was found to be a good promotor in this reaction
system, giving the product in 72% yield (entry 4). Anhydrous LiI
was less effective (entry 5), but NaI and KI were relatively
effective (entries 6 and 7). In the case of LiBr and LiCl, the
reactions proceeded at much lower rate, affording the product in
60% and 46% yields, respectively (entries 8 and 9). Since it was
evident that the solvent influenced the efficiency of the reaction,
we next examined LiI·2H2O-promoted [4+1] cycloaddition using
different solvents. When toluene was used as a solvent, the
reaction proceeded smoothly to afford the product 3aa in 74%
yield, although the reaction system has slightly complicated
compared with the use of dioxane as a solvent (entry 10).
Dichloroethane (DCE) and propionitrile were not particularly
effective, affording the product only in moderate yields (entries
11 and 12).
6
NaI
69
7
KI
64
8
LiBr
60
9
LiCl
46
10
11
12
LiI·2H2O
LiI·2H2O
LiI·2H2O
74
50
propionitrile
59
As mentioned above, 2-mercaptobenzaldehyde derivatives 1
were good substrates for [4+1] cycloaddition of isocyanides, but
these have an unpleasant smell, are unstable, and are difficult to
be isolated in good yields. Therefore, we decided to use the
corresponding disulfide compounds 4, which are easier to store,
as substrates.
Next, we attempted to expand the range of isocyanides 2 and
2-mercaptobenzaldehyde derivatives 1 that can be used in the
Passerini-type [4+1] cycloaddition reaction with LiI·2H2O as a
promoter, as detailed in Table 2. The reaction of aliphatic
isocyanides 2a and 2b (R2 = t-Oct and t-Bu) with 1a in the
presence of LiI·2H2O gave the products in good yields (entries 1
and 2), while the secondary and primary aliphatic isocyanides 2c
and 2d were not applicable to the reaction (entries 3 and 4).
However, isocyanides 2e–2h reacted with 1a to afford the desired
products (entries 5–8). We also investigated substituted 2-
mercaptobenzaldehyde derivatives bearing an electron-donating
or an electron-withdrawing group on the aromatic ring (entries 9–
11). The reactions proceeded to afford the corresponding
We examined whether the disulfide derivative 4a was capable
of participating in
a Passerini-type reaction with t-octyl
isocyanide (2a) in the presence of MgCl2, ZnCl2 and other metal
halides in refluxing toluene (Table 3). Although trace amounts of
product were observed in the absence of any promoter, the
desired 3aa was obtained in low yield in the presence of MgI2,
ZnI2, and CuI (entries 1–4). When LiI·2H2O was used as a
promoter, the substrate was consumed in 3 h, affording the

3
product in 84% yield (entry 5). Anhydrous LiI was also effective
observed when disulfide 5c, which has a methoxy group at the
3-position, was used, giving the product in 6% yield (entry 9).
ACCEPTED MANUSCRIPT
in this reaction, although NaI and KI were not (entries 6–8).
When LiBr or LiCl was used, the reaction proceeded very slowly
to afford the product in 70% or 17% yield, respectively, after 48
h (entries 9 and 10). We found that NIS, NBS, and NCS were not
effective as promoters (entries 11–13). The reaction proceeded
efficiently in toluene and dioxane to afford 3aa in high yields
(entries 6 and 14). The use of DMF, dichloroethane (DCE), or
propionitrile as a solvent was less effective, resulting in the
formation of 3aa in yields of 20, 37, and 66%, respectively
(entries 15–17).
Table 3 Results of Passerini-type [4+1] cycloaddition reaction
under various conditions
Table 2 Range of isocyanides and 2-mercaptobenzaldehyde
derivatives applicable to the Passerini-type [4+1]
cycloaddition reaction.
Entry
1
Promoter
-
solv.
Time / h
23
15
24
24
3
Yield / %
trace
23
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
dioxane
DMF
2
MgI2
ZnI2
3
31
4
CuI
35
5
LiI·2H2O
LiI
84
6
3
69
Entry
1
R1
R2
Yield / %
72 (3aa)
54 (3ab)
7
NaI
24
24
48
48
24
24
24
24
24
24
1
nr
H (1a)
H (1a)
H (1a)
H (1a)
H (1a)
H (1a)
H (1a)
H (1a)
t-Bu (1b)
MeO (1c)
Cl (1d)
t-Oct (2a)
8
KI
nr
2
t-Bu (2b)
9
LiBr
70
a
3
c-Hex (2c)
Bn (2d)
-
10
11
12
13
14
15a
16
17
LiCl
17
a
4
-
b
NIS
-
5
6b
Ph (2e)
51 (3ae)
27 (3af)
66 (3ag)
31 (3ah)
77 (3ba)
47 (3ca)
51 (3da)
b
NBS
-
4-MeOC6H4 (2f)
4-Me2NC6H4 (2g)
4-BrC6H4 (2h)
t-Oct (2a)
b
NCS
-
7
LiI·2H2O
LiI·2H2O
LiI·2H2O
94
20
37
66
8
9
DCE
10
11
t-Oct (2a)
LiI·2H2O propionitrile
t-Oct (2a)
a Complex mixture. b The reaction was quenched after 20 h.
a Reaction was carried out at 100 °C. b Complex mixture.
To gain a mechanistic insight into this reaction, a series of
control experiments were rationally designed and performed.
When the reaction of 2-mercaptobenzaldehyde (1a) with tert-
octyl isocyanide (2a) was carried out in the presence of TEMPO
as a radical scavenger, disulfide 4a was obtained in 75% yield as
a major product and the desired 3aa was obtained only in 7%
yield (eq 2). In the case of disulfide 4a with 2a in the presence of
TEMPO, the reaction was sluggish, affording 3aa in 33% yield
(eq 3). In addition, homolytic cleavage of the S-S bond was
observed in refluxing dioxane. Thus, when the mixture of 4a and
4d was heated in dioxane, the heterocoupling disulfide 4e was
obtained in 67% yield (eq 4). Since the desired product was not
obtained from aldehydes in the absence of LiI·2H2O, it was
concluded that Li+ acts as a Lewis acid to activate the carbonyl
group (Table 1, entry 1).
We subsequently attempted to expand the range of
isocyanides and disulfide derivatives that could be used in the
[4+1] cycloaddition reaction, using LiI·2H2O in all cases, as
detailed in Table 4. In these reactions, optimal molar quantities of
disulfide derivatives 4a, 4e, and 4c (1.0 equiv) and isocyanides
2a–g (3.0 equiv) were used in the presence of 1.0 equiv of
LiI·2H2O under reflux in dioxane. The reaction of aliphatic
isocyanides 2a and 2b (R2 = t-Oct, t-Bu) with 4a in the presence
of LiI·2H2O gave the products in good to high yield (entries 1–
2). In the case of secondary and primary aliphatic isocyanides 2c
and 2d, the product mixture was complex and the desired
benzothiophene derivatives 3 were not obtained (entries 3–4).
Aromatic isocyanides were also investigated, but they showed
very low reactivity (entries 5–7). Even aromatic isocyanides
bearing an electron-donating group at the para position exhibited
low reactivity, with low product yield (entry 7). We also
investigated substituted disulfide derivatives bearing an electron-
donating group. In the case of disulfide 4e, which has a methyl
group at the 3-position, the reaction proceeded efficiently to
afford the product in high yield (entry 8). Lower reactivity was
Based on these results, reaction mechanisms were proposed
for the Passerini-type [4+1] cycloaddition reaction from the two
substrates 1 and 4, as shown in Scheme 2. In the case of 2-
mercaptobenzaldehyde 1, Li+ acts as a Lewis acid, coordinating
to the aldehyde. Passerini-type nucleophilic attack of the
isocyanide generates the nitrilium intermediate A. This

4
Tetrahedron
ACCEPTED MANUSCRIPT
intermediate is subsequently trapped by the thiol to afford
adduct B. Finally, aerobic oxidation of the resulting alcohol
proceeds to afford the corresponding benzothiophene derivative 3
(path 1). When 4 is used as a substrate, thermal homolytic
cleavage of S-S bond is initiated to afford the thiyl radical C,9
which intramolecularly abstracts the hydrogen of the aldehyde,
giving the acyl radical D. The other generated thiyl radical C
abstracts the hydrogen from the thiol group of D to afford the
biradical E and 2-mercaptobenzaldehyde 1. [4+1] Cycloaddition
between E and isocyanide 2 proceeds via radical reaction to
afford the desired benzothiophene derivative 3 (path 2-A), and
product 1 reacts with isocyanide in a similar way to Path 1 (Path
2-B).
Table 4 Range of isocyanides and disulfide derivatives
applicable to the Passerini-type [4+1] cycloaddition reaction
3. Conclusion
Entry
R1
R2
Time /
h
Yield / %
We developed a [4+1] cycloaddition reaction of isocyanides
with 2-mercaptobenzaldehydes and their disulfide derivatives,
promoted by LiI·2H2O, which affords benzothiophene
derivatives in moderate to good yields. Various types of
isocyanides, 2-mercaptobenzaldehydes and disulfide derivatives
were used successfully in the reaction.
1
2
3
4
5
6
7
8
9
H (4a)
H (4a)
t-Oct (2a)
t-Bu (2b)
24
20
24
24
24
24
22
24
44
94 (3aa)
72 (3ab)
a
H (4a)
c-Hex (2c)
Bn (2d)
-
a
H (4a)
-
4. Experimental Section
H (4a)
Ph (2e)
nr
1H NMR spectra were recorded on a 400 MHz NMR
spectrometer. Chemical shifts δ are reported in ppm using TMS
as an internal standard. Data are reported as follows: chemical
shift, multiplicity (s = singlet, d = doublet, t = triplet, q = quartet,
m = multiplet), coupling constant (J) and integration. 13C NMR
spectra were recorded on 100 MHz NMR spectrometer. The
chemical shifts were determined in the δ-scale relative to CDCl3
(δ = 77.0 ppm). The wave numbers of maximum absorption
peaks of IR spectroscopy are presented in cm−1. HRMS (FAB
positive, DART) was measured with a quadrupole mass
spectrometer and TOF mass spectrometers. All melting points
H (4a)
4-MeOC6H4 (2f)
4-Me2NC6H4 (2g)
t-Oct (2a)
nr
H (4a)
6 (3ag)
97 (3da)
6 (3ca)
Me (4e)
MeO (4c)
t-Oct (2a)
a Complex mixture.
were measured using
a micro melting point apparatus.
Dehydrated solvents were purchased for the reactions and used
without further desiccation.
General procedure (Table 2)
To a solution of 1 (0.3 mmol) and 2 (0.45 mmol) in dioxane
(3.0 mL), LiI·2H2O (0.3 mmol) was added and the whole was
stirred at 110 °C. After reaction completion (monitored by TLC),
the solvent was removed in vacuo. The crude was purified by
silica gel column chromatography.
In the case of Table 4, 4 (0.3 mmol) and 2 (0.9 mmol) were used
as substrates.
(Z)-2-((2,4,4-trimethylpentan-2-
yl)imino)benzo[b]thiophen-3(2H)-one (3aa) (Table 4, entry 1)

5
Silica gel column chromatography (hexane/diethyl ether =
10/1) gave 3aa (155 mg, 94% yield) as a brown oil. H NMR
ACCEPTED MANUSCRIPT
1
(Z)-2-((4-bromophenyl)imino)benzo[b]thiophen-3(2H)-one
(CDCl3): 0.89 (s, 9H), 1.42 (s, 6H), 1.79 (s, 2H), 7.20 (m, 1H),
7.33 (d, J = 8.0 Hz, 1H), 7.51 (m, 1H), 7.80 (d, J = 8.0 Hz, 1H).
13C NMR (CDCl3): 28.7, 31.5, 32.0, 54.5, 62.5, 124.4, 126.1,
127.2, 127.5, 136.5, 144.9, 147.3, 185.6. IR (KBr): 2950, 1710,
1630, 1590, 1450, 1390, 1280, 1070, 1030 cm–1. HRMS–FAB
(m/z): Calcd for C16H22NOS [M+H]+: 276.1422. Found:
276.1422.
(3ah) (Table 2, entry 5)
Silica gel column chromatography (hexane/diethyl ether =
6/1) gave 3ah (29 mg, 31% yield) as a glay solid of mp = 150–
151 °C (hexane/ethyl acetate). 1H NMR (CDCl3): 7.08 (d, J = 8.0
Hz, 2H), 7.27–7.36 (m, 2H), 7.51 (d, J = 8.0 Hz, 2H), (m, 1H),
7.57 (m, 1H), 7.91 (d, J = 8.0 Hz, 1H). 13C NMR (CDCl3): 120.8,
122.7, 124.9, 126.9, 127.6, 127.9, 132.5, 137.1, 144.0, 148.2,
157.1, 185.2. IR (KBr): 2960, 1700, 1650, 1560, 1480, 1300,
1280, 1070 cm–1. HRMS–DART (m/z): Calcd for C14H9BrNOS
[M+H]+: 317.9588. Found: 317.9591.
(Z)-2-(tert-butylimino)benzo[b]thiophen-3(2H)-one (3ab)
(Table 4, entry 2)
Silica gel column chromatography (hexane/diethyl ether =
1
10/1) gave 3ab (95 mg, 72% yield) as a brown oil. H NMR
(Z)-5-(tert-butyl)-2-((2,4,4-trimethylpentan-2-
yl)imino)benzo[b]thiophen-3(2H)-one (3ba) (Table 2, entry 9 )
(CDCl3): 1.42 (s, 9H), 7.21 (m, 1H), 7.34 (d, J = 7.8 Hz, 1H),
7.52 (m, 1H), 7.82 (d, J = 7.8 Hz, 1H). 13C NMR (CDCl3): 28.5,
58.6, 124.4, 126.1, 127.1, 127.4, 136.6, 144.5, 149.1, 185.8. IR
(KBr): 2970, 1720, 1620, 1590, 1450, 1390, 1360, 1280, 1230,
1070, 1030 cm–1. HRMS–DART (m/z): Calcd for C12H14NOS
[M+H]+: 220.0796. Found: 220.0793.
Silica gel column chromatography (hexane/diethyl ether =
10/1) gave 3ba (76 mg, 77% yield) as a brown oil. H NMR
1
(CDCl3): 0.91 (s, 9H), 1.27 (s, 9H), 1.44 (s, 6H), 1.80 (s, 2H),
7.27 (d, J = 8.4 Hz, 1H), 7.57 (dd, J = 2.4, 8.4 Hz, 1H), 7.84 (d, J
= 2.4 Hz, 1H). 13C NMR (CDCl3): 28.8, 31.1, 31.5, 32.0, 34.7,
54.3, 62.5, 124.0, 124.2, 126.9, 134.3, 141.2, 148.2, 149.7, 185.9.
IR (KBr): 2960, 1700, 1640, 1490, 1360, 1280, 1190, 1030 cm–1.
HRMS–DART (m/z): Calcd for C20H30NOS [M+H]+: 332.2048.
Found: 332.2036.
(Z)-2-(phenylimino)benzo[b]thiophen-3(2H)-one
(3ae)
(Table 2, entry 5)
Silica gel column chromatography (hexane/diethyl ether =
6/1) gave 3ae (36 mg, 51% yield) as a pale orange solid of mp =
1
151–152 °C (hexane/ethyl acetate). H NMR (CDCl3): 7.23–7.62
(Z)-5-methoxy-2-((2,4,4-trimethylpentan-2-
yl)imino)benzo[b]thiophen-3(2H)-one (3ca) (Table 2, entry 10)
(m, 8H), 7.94 (d, J = 7.6 Hz, 1H). 13C NMR (CDCl3): 121.0,
124.9, 126.7, 127.3, 127.8, 129.3, 136.9, 144.5, 149.6, 156.4,
185.4. IR (KBr): 2970, 1710, 1620, 1600, 1450, 1290, 1220 cm–1.
HRMS–DART (m/z): Calcd for C14H10NOS [M+H]+: 240.0483.
Found: 240.0481.
Silica gel column chromatography (hexane/diethyl ether =
3/1) gave 3ca (51 mg, 47% yield) as a brown oil. H NMR
1
(CDCl3): 0.96 (s, 9H), 1.47 (s, 6H), 1.84 (s, 2H), 3.82 (s, 3H),
7.17 (dd, J = 2.4, 8.4 Hz, 1H), 7.27 (d, J = 8.4 Hz, 1H), 7.36 (d, J
= 2.4 Hz, 1H). 13C NMR (CDCl3): 28.7, 31.5, 31.9, 54.3, 55.7,
62.5, 109.7, 125.1, 125.5, 127.9, 136.4, 148.4, 158.3, 185.7. IR
(KBr): 2960, 1710, 1620, 1570, 1480, 1360, 1300, 1280, 1080,
1030 cm–1. HRMS–DART (m/z): Calcd for C17H24NO2S [M+H]+:
306.1528. Found: 306.1516.
(Z)-2-((4-methoxyphenyl)imino)benzo[b]thiophen-3(2H)-
one (3af) (Table 2, entry 6)
Silica gel column chromatography (hexane/diethyl ether =
6/1) gave 3af (22 mg, 27% yield) as a pale orange solid of mp =
1
146–147 °C (hexane/ethyl acetate). H NMR (CDCl3): 3.85 (s,
3H), 7.00 (d, J = 9.2 Hz, 2H), 7.34 (m, 1H), 7.41 (d, J = 9.2 Hz,
2H), 7.43 (m, 1H), 7.58 (m, 1H), 7.95 (d, J = 8.0 Hz, 1H). 13C
NMR (CDCl3): 55.5, 114.5, 124.6, 124.8, 126.6, 127.6, 127.8,
136.6, 141.3, 144.5, 152.5, 159.5, 185.7. IR (KBr): 2850, 1700,
1600, 1560, 1500, 1460, 1290, 1260, 1180, 1040 cm–1. HRMS–
DART (m/z): Calcd for C15H12NO2S [M+H]+: 270.0589. Found:
270.0592.
(Z)-5-chloro-2-((2,4,4-trimethylpentan-2-
yl)imino)benzo[b]thiophen-3(2H)-one (3da) (Table 2, entry 11)
Silica gel column chromatography (hexane/diethyl ether =
10/1) gave 3da (48 mg, 51% yield) as a brown oil. H NMR
1
(CDCl3): 0.98 (s, 9H), 1.45 (s, 6H), 1.79 (s, 2H), 7.29 (d, J = 8.4
Hz, 1H), 7.49 (dd, J = 2.4, 8.4 Hz, 1H), 7.79 (d, J = 2.4 Hz, 1H).
13C NMR (CDCl3): 28.7, 31.6, 32.0, 54.6, 62.7, 125.6, 127.2,
128.2, 132.4, 136.4, 143.0, 146.7, 184.5. IR (KBr): 2950, 1720,
1630, 1590, 1560, 1450, 1360, 1290, 1250, 1220, 1080 cm–1.
HRMS–DART (m/z): Calcd for C16H21ClNOS [M+H]+:
310.1032. Found: 310.1023.
(Z)-2-((4-(dimethylamino)phenyl)imino)benzo[b]thiophen-
3(2H)-one (3ag) (Table 2, entry 7)
Silica gel column chromatography (hexane/ethyl acetate =
3/1~1/1) gave 3ag (56 mg, 66% yield) as a brown solid of mp =
1
172–173 °C (hexane/ethyl acetate). H NMR (CDCl3): 3.07 (s,
(Z)-5-methyl-2-((2,4,4-trimethylpentan-2-
yl)imino)benzo[b]thiophen-3(2H)-one (3ea) (Table 2, entry 8 )
6H), 6.79 (d, J = 8.8 Hz, 2H), 7.32 (t, J = 7.6 Hz, 1H), 7.46 (d, J
= 7.6 Hz, 1H), 7.54 (d, J = 8.8 Hz, 2H), 7.59 (t, J = 7.6 Hz, 1H),
7.96 (d, J = 7.6 Hz, 1H). 13C NMR (CDCl3): 40.2, 112.0, 124.6,
126.2, 126.7, 127.3, 128.2, 135.8, 135.9, 144.5, 146.8, 150.6,
186.0. IR (KBr): 2960, 1700, 1640, 1530, 1380, 1290, 1240,
1180, 1020 cm–1. HRMS–DART (m/z): Calcd for C16H15N2OS
[M+H]+: 283.0905. Found: 283.0897.
Silica gel column chromatography (hexane/diethyl ether =
10/1) gave 3ea (90 mg, 97% yield) as a pale yellow solid of mp =
79–80 °C (hexane/ethyl acetate). 1H NMR (CDCl3): 0.96 (s, 9H),
1.45 (s, 6H), 1.84 (s, 2H), 2.35 (s, H), 7.28 (d, J = 8.4 Hz, 1H),
7.39 (d, J = 8.4 Hz, 1H), 7.68 (s, 1H). 13C NMR (CDCl3): 20.6,
28.5, 31.4, 31.7, 54.2, 62.2, 124.0, 126.9, 127.3, 136.0, 137.4,
141.5, 147.8, 185.5. IR (KBr): 2950, 1710, 1630, 1600, 1570,

6
Tetrahedron
ACCEPTED MANUSCRIPT
1470, 1380, 1300, 1280, 1230, 1160, 1080 cm–1. HRMS–DART
W.; McDevitt, R.; Adebayo, F. O.; Sawicki, D. R.; Seestaller, L.;
(m/z): Calcd for C17H24NOS [M+H]+: 290.1579. Found:
290.1570.
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Supplementary Material
Supplementary material that may be helpful in the review
process should be prepared and provided as a separate electronic
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Acknowledgments
This work was supported by a Grant-in-Aid for Young
Scientists (B) (24750037), a Grant-in-Aid for Scientific Research
(B) from the Japan Society for the Promotion of Science
(24350022), Kanazawa University CHOZEN Project, and
Kanazawa University SAKIGAKE Project.