Studies on chalcogen-containing heterocycles. Part 38: Regio- and stereoselective tandem addition-iodocyclization of 2-ethynylphenyl isothiocyanates with N- and O-nucleophiles affording 4-(iodoalkylidene)benzo[d] [1,3]thiazines

Article abstract of DOI:10.1016/j.tet.2013.05.069

The treatment of the o-ethynylphenyl isothiocyanates with primary and secondary amines in 1,2-DCE, followed by the addition of I₂ and then heating resulted in the regio- and stereoselective tandem addition- iodocyclization to give the (4E)-2-am

Full text of DOI:10.1016/j.tet.2013.05.069

Tetrahedron 69 (2013) 6478e6487
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Studies on chalcogen-containing heterocycles. Part 38: Regio- and
stereoselective tandem additioneiodocyclization of 2-ethynylphenyl
isothiocyanates with N- and O-nucleophiles affording
4-(iodoalkylidene)benzo[d][1,3]thiazinesy
,
a
b
Haruki Sashida a , Mamoru Kaname , Mao Minoura
*
a Faculty of Pharmaceutical Sciences, Hokuriku University, Kanagawa-machi, Kanazawa 920-1181, Japan
b Department of Chemistry, School of Science, Kitasato University, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa 252-0373, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
The treatment of the o-ethynylphenyl isothiocyanates with primary and secondary amines in 1,2-DCE,
followed by the addition of I2 and then heating resulted in the regio- and stereoselective tandem ad-
ditioneiodocyclization to give the (4E)-2-amino-4-(1-iodomethylidene)benzo[d][1,3]thiazine derivatives
as the sole product in high yields via the 6-exo-dig mode cyclization. The 2-alkoxy-1,3-benzothiazines
were similarly produced from the o-ethynylphenyl isothiocyanates and the corresponding sodium
alkoxides.
Received 12 November 2012
Received in revised form 16 May 2013
Accepted 20 May 2013
Available online 23 May 2013
Keywords:
1,3-Benzothiazine
Isothiocyanate
Ó 2013 Elsevier Ltd. All rights reserved.
Tandem addition-cyclization
Iodocyclization
6-exo-dig Mode
1. Introduction
heterocyclic compounds is a very important methodology because
the starting material, i.e., alkynes, are easily obtained from com-
The preparation of benzo[d][1,3]thiazine derivatives is of con-
tinuing interest in the field of synthetic organic chemistry because
of their biological and pharmaceutical activities.2 There are many
efficient synthetic methods for the benzo[d][1,3]thiazines3 in-
volving the classical method, which is the condensation of 2-
aminobenzyl chloride with thioamides or thioureas. Recently,
mercially available compounds via the Sonogashira palladium
coupling. Furthermore, the obtained iodoheterocycles can be the
starting materials for the preparation of the more functionalized
heterocyclic compounds through the CeC bond formation by
a cross-coupling reaction, such as the Sonogashira or Suzuki
reactions.
a
2-amino(imino)-4-methylidene-4H-benzo[d][1,3]thiazine syn-
While iodocyclization of the 2-ethynyl-phenol, -aniline or -thiol
derivatives has been utilized for the synthetic approach to five-
membered heterocycles, such as the benzo[b]furans,8 indoles,9
and benzo[b]thiophenes,10 there are only a few studies concern-
ing the synthesis of six-membered heterocycles11 except for the
isocoumarins12 by the 6-endo-dig type cyclization of the o-ethy-
nylbenzoate ester derivatives and seven-membered heterocycles.13
Recently, the 3-iodoselenophenes14 and 3-iodobenzoseleno
phenes15 were also prepared by a similar protocol. These prod-
ucts were transformed into the 2,3-disubstituted benzo[b]heteroles
involving valuable biologically active compounds. The accom-
plishment of these iodocyclizations is dependent on the nature of
the substituent directly linked to the heteroatoms; a substituent,
such as the methyl, benzyl or acetyl group, is needed as the leaving
group in most cases. Very recently, we described the tandem
thesis protocol, which is the tandem 6-exo-dig mode addition-
cyclization reactions of the 2-ethynylanilines with the iso-
thiocyanates and related compounds, has attracted considerable
attention; these reactions are often promoted by a silver catalyst,4
DMAP5a or silica gel.5b The 2-thioformylaminodiphenylacetylenes
were cyclized by DBU to give the 2-unsubstituted 3,1-
benzothiazines.6
Electrophilic cyclization involving the iodocyclization7 approach
with the heteroatom-containing arylalkynes for preparing the
* Corresponding author. Tel.: þ81 76 229 6211; fax: þ81 76 229 2781; e-mail
address: h-sashida@hokuriku-u.ac.jp (H. Sashida).
y
See Ref. 1.
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.05.069

H. Sashida et al. / Tetrahedron 69 (2013) 6478e6487
6479
additioneiodocyclization of o-ethynylphenyllithiums with iso-
selenocyanates, followed by treatment with I2 to give the (E)-1-
(iodomethylidene)benzo[c]selenophenes in one pot.16 Two in-
dependent groups17 have already studied the 6-exo-trig mode
iodocyclization of the N-homoallyl thioureas and thioamides
leading to the monocyclic 1,3-thiazine derivatives. There have been
no studies on the synthesis of the 3,1-benzothiazines via the 6-exo-
dig mode iodocyclization.
reaction was conducted to examine the optimal reaction condi-
tions; these results are shown in Table 1.
The adduct, N-(2-ethynylphenyl)thiourea 4 generated from
the isothiocyanate 1A and diethylamine 2a, was regio- and
stereoselectively iodocyclized to the 1,3-thiazine 3Aa in 51% yield
in the presence of Cs2CO3 as a base in CH2Cl2 at room tempera-
ture (entry 1). When 1A was similarly treated with 2a and Cs2CO3
in the absence of I2, the thiourea 4 was isolated in 91% yield
(entry 2), then converted into the thiazine 3Aa in high yield using
I2 in CH2Cl2. The 1,3-thiazine 3Aa was produced in 60% yield with
the use of refluxing CH2Cl2 (entry 3). However, 3Aa was produced
without the use of an inorganic base in only 5% yield together
with 4 in 16% yield (entry 4). Similar results were obtained using
an excess of 2a (entry 5). Thus, the use of an inorganic base is
essential, while an organic base was not effective. The 1,3-
thiazine 3Aa was produced by the reaction in the presence of
K2CO3 and Na2CO3 instead of Cs2CO3 in 30% and 21% yields, re-
spectively (entries 6, 7). The 1,3-thiazine 3Aa was found to be
obtained in the highest yields, of 83% in 1,2-dichloroethane (DCE)
at 65 ꢀC (entry 8). On the other hand, the use of dry THF as the
solvent at room temperature gave a complex mixture involving
the thiourea 4; the desired iodothiazine 3Aa was not obtained
(entry 9). The reaction at 60 ꢀC in THF gave 3Aa in only 21% yield
(entry 10). The isothiocyanate 1A was reacted with 1.1 mmol of
diethylamine 2a, followed by treatment with I2 in CH3CN to give
the bis-diethylamino derivative 5 in 50% yield through the 1:2
addition in one pot together with the thiourea 4 (entry 11). Using
2.2 mmol of diethylamine 2a gave 5 in 86% yield as the sole
product (entry 12). Generally, the use of a more polar solvent,
such as CH3CN, is favored for the iodocyclization concerning the
triple bond due to the solubility of I2 and inorganic bases, such as
NaHCO3, K2CO3, and Cs2CO3.7 However, this theory did not agree
with the present experimental facts; the use of a less polar sol-
vent (1,2-DCE) gave the best result. The solvent effects on the
iodocyclization are quite drastic, but cannot be clearly explained
at the present.
In this study, as a part of our continuing studies,16,18,19 we de-
scribe the first examples of the one-pot preparation of the (4E)-4-
(1-iodomethylidene)benzo-1,3-thiazines by addition of the o-
ethynylphenyl isothiocyanates with N- and O-nucleophiles, fol-
lowed by iodocyclization of the thiourea or thiourethane adducts.
While the silver-catalyzed tandem addition-cyclization of the o-
ethynylphenyl isothiocyanates with the secondary amines pro-
ceeded in both the 6-exo-dig and 5-endo-dig mode cyclizations as
reported in a previous study,20 in this iodocyclization, using both
the primary and secondary amines afforded only the 6-exo-dig
mode products, i.e., the (4E)-2-amino-4-(1-iodomethylidene)-4H-
benzo[d][1,3]thiazines in high yields. The isothiocyanates also
reacted with the alkoxides to give the corresponding benzo[d][1,3]
thiazines having an oxygen-functional group at the 2-position.
Iodocyclization using the isothiocyanates requires no leaving
groups on the sulfur element in this case and has the advantage of
a high atom-economy.
2. Results and discussion
2.1. Reaction of 2-ethynylphenyl isothiocyanate with dieth-
ylamine and I2: optimization of reaction conditions
The treatment of the o-ethynylphenyl isothiocyanate 1A with
diethylamine 2a, followed by the addition of I2 resulted in the
tandem addition-6-exo-dig mode cyclization to give the (4E)-2-
amino-4-(1-iodomethylidene)-4H-benzo[d][1,3]thiazine 3Aa as
the sole product in one pot. This tandem additioneiodocyclization
Table 1
Reaction of 2-ethynylphenyl isothiocyanate 1A with diethylamine 2a and I2
Entry
Diethylamine 2a
I2
Base
Solvent
Temp
Producta,b (%)
1
2
3
4
5
6
7
8
1.1 mmol
0.1 mmol
1.1 mmol
1.1 mmol
4.0 mmol
1.1 mmol
1.1 mmol
1.1 mmol
1.1 mmol
1.1 mmol
1.1 mmol
2.2 mmol
1.3 mmol
None
Cs2CO3, 1.5 mmol
Cs2CO3, 1.5 mmol
Cs2CO3, 1.5 mmol
None
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
1,2-DCE
THF
rt
rt
3Aa (51%)
4 (91%)
1.3 mmol
1.3 mmol
1.3 mmol
1.3 mmol
1.3 mmol
1.3 mmol
1.3 mmol
1.3 mmol
1.3 mmol
1.3 mmol
Reflux
Reflux
Reflux
Reflux
Reflux
65 ꢀC
rt
60 ꢀC
rt
rt
3Aa (60%)
3Aa (5%), 4 (16%)
3Aa (7%), 4 (20%)
3Aa (30%)
3Aa (21%)
3Aa (83%)
4 (30%)
3Aa (21%)
5 (50%)
5 (86%)
None
K2CO3, 1.5 mmol
Na2CO3, 1.5 mmol
Cs2CO3, 1.5 mmol
Cs2CO3, 1.5 mmol
Cs2CO3, 1.5 mmol
Cs2CO3, 1.5 mmol
Cs2CO3, 1.5 mmol
9
10
11
12
THF
CH3CN
CH3CN
a
Isolated yield.
The reaction was carried out for 3e5 h.
b

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H. Sashida et al. / Tetrahedron 69 (2013) 6478e6487
2.2. Reaction of 2-ethynylphenyl isothiocyanates with sec-
ondary amines and I2: formation of (4E)-2-amino-4-(1-iodo
methylidene)benzo[d][1,3]thiazines
extending the substrates to the o-ethynylphenyl isothiocyanates 1B
and 1C having a bulky alkyl or TMS group at the sp-carbon atom of
the ethynyl moiety with diethylamine 2a. The reaction of 2-(3,3-
dimethylbut-1-ynyl)phenyl isothiocyanate 1B with diethylamine
2a, followed by the addition of I2 gave the (4E)-2-amino-4-(1-
iodomethylidene)-4H-benzo[d][1,3]thiazine 3Ba in 90% yield (en-
try 5).
On the contrary, neither the TMS 3Ca nor the desilylated de-
rivative 3Ca0 was obtained. The iodocyclized product 3Ca from the
reaction of 1C with 2a might be too unstable to isolate (entry 6).
The generality of this tandem additioneiodocyclization of o-
ethynylphenyl isothiocyanates 1A with other secondary amines
involving the aliphatic cyclic and aromatic amines, and the sub-
strates having an alkyl and phenyl group at the triple bond, was also
performed (Table 2). The treatment of 1A with secondary cyclic
amines, such as piperidine 2b, pyrrolidine 2c, and morpholine 2d,
followed by the addition of I2 gave the corresponding (4E)-2-
amino-4-(1-iodomethylidene)-4H-benzo[d][1,3]thiazines
3Ab,
2.3. Reaction of 2-ethynylphenyl isothiocyanates with pri-
mary amines and I2: formation of (4E)-2-imono-4-(1-iodome
thylidene) benzo[d][1,3]thiazines
3Ac, and 3Ad in 89, 88, and 95% yields, respectively (entries 1e3).
This tandem reaction proceeded with the aromatic amine, N-
methylaniline 2e, to afford the 2-anilino derivative 3Ae in 91%
yield (entry 4). In order to demonstrate the efficiency of this tan-
dem additioneiodocyclization, the generality was explored by
Next, the o-ethynylphenyl isothiocyanates 1 and the prim
ary amines 6 were also found to regio- and stereoselectively
Table 2
(4E)-2-Amino-3 and (4E)-2-imino-4-(1-iodomethylidene)benzo[d][1,3]thiazines 7a
Entry
1
Isocyante
Amine
Reaction time (h)
Product
Yieldb (%)
Piperidine 2b
2.5
89
2
3
1A
1A
1A
Pyrrolidine 2c
Morpholine 2d
3
3
88
95
4
5
N-Methylaniline 2e
Diethylamine 2a
3.5
3.5
91
90
6
7
2a
7
7
00c
1A
1A
tert-Butylamine 6a
78
8
n-Butylamine 6b
4
66

H. Sashida et al. / Tetrahedron 69 (2013) 6478e6487
6481
Table 2 (continued )
Entry
Isocyante
Amine
Reaction time (h)
Product
Yieldb (%)
9
1A
Cyclohexylamine 6c
6
81
10
11
1A
1A
Benzylamine 6d
5
7
81
84
Aniline 6e
12
1B
6a
4
52
a
Standard reactions conditions: 1 (1 mmol), 2 (1.1 mmol), I2 (1.3 mmol), Cs2CO3 (1.5 mmol), dry DCE (2.0 mL), 65 ꢀC.
Isolated yield.
Decomposed.
b
c
proceed, affording the corresponding (4E)-2-imino-4-(1-iodometh
isomerization of the isolated products under daylight was ob-
served; The 1H NMR analysis showed that 3Da-E easily isomerized
into 3Da-Z in CDCl3 at room temperature within 30 min in excellent
yield. The double-doublets signal at 8.01 ppm that was assigned to
the 5-H proton on the benzene-ring of 3Da-E disappeared, and fi-
nally obtained a 1H NMR signal that was in good agreement with
that of 3Da-Z.
This stereospecific iodocyclization of the isocyanate 1D with the
primary amine, tert-butylamine 6a, similarly proceeded to give the
tert-butyl derivatives 7Da-E and 7Da-Z under the dark and daylight
conditions in 78 and 77% yields, respectively (Scheme 1).
ylidene)-4H-1,2-dihydrobenzo[d][1,3]thiazines 7 as shown in Table
2. The o-ethynylphenyl isothiocyanate 1A was similarly treated with
tert-butylamine 6a, followed by iodination with I2 in DCE at 65 ꢀC,
giving the desired (4E)-2-imino-4H-1,2-dihydro benzo[d][1,3]thia-
zine 7Aa in one pot in 78% yield (entry 7). Compound 1A reacted with
the otheraliphatic amines, suchasn-butylamine 6b, cyclohexylamine
6c, and benzylamine 6d, to give the corresponding (4E)-1,3-thiazines
7Ab, 7Ac, 7Ad in 66, 81, and 81% yields, respectively (entries 8e10).
The aromatic amine, aniline 6e, also reacted with the isothiocyanate
1A to give the phenylimino derivative 7Ae in 84% yield (entry 11). The
o-(tert-butylethynyl)phenyl isothiocyanate 1B also reacted with tert-
butylamine 6a to afford the neopentylidene 7Ba in 52% yield (entry
12). The addition reaction of the primary amines 6 with the iso-
thiocyanate 1 required a relatively long reaction time due to the lower
nucleophilicity of the primary amines than that of the secondary
amines.
2.5. Structure of (4E)-4-(1-iodomethylidene)benzo-1,3-th
iazines
The structures of these 3,1-thiazines 3 and 7 were mainly de-
termined by their MS, 1H, and 13C NMR spectra and elemental
analyses, and finally, the cyclization mode and olefin geometry
were established by single-crystal X-ray studies using 7Ae and 3Da-
Z, which were obtained in the crystalline states. The ORTEP draw-
ings are shown in Figs. 1 and 2, respectively.21
2.4. Reaction of 2-(phenylethynyl)phenyl isothiocyanate with
amines and I2
Interestingly, the reaction of 2-(phenylethynyl)phenyl iso-
thiocyanate 1D with the secondary amine, diethylamine 2a, under
the daylight conditions, which were previously used for the prep-
2.6. Reaction of 2-hexynylphenyl isothiocyanate with O-nu
cleophiles
aration
of (4E)-4-(1-iodomethylidene)benzo[d][1,3]-thiazines
3Aaee, 3Ba, 7Aaee, and 7Ba, produced the stereoisomer, the (Z)-
iodomethylidene derivative 3Da-Z, in 77% yield as the sole product;
no normal desired (E)-derivative 3Da-E was obtained. Thus, this
tandem reaction was performed under dark conditions (reaction
and other operations including the purification) using 1D and 2a;
the (E)-derivative 3Da-E was isolated in 90% yield. These results for
the formation of the (E)-3Da-E and (Z)-derivatives 3Da-Z clearly
indicated the following: the isomerization from 3Da-E into 3Da-Z is
effective by direct light absorption due to having a typical photo-
sensitive trans-styrene moiety. Furthermore, the (E)/(Z)
The similar regio- and stereoselective tandem addi-
tioneiodocyclization is also applicable to the o-ethynylphenyl iso-
thiocyanate with O-nucleophiles, with the results being
summarized in Scheme 2. In this case, the adducts from the o-
ethynylphenyl isothiocyanate 1A and the alkoxides 8 were isolated.
The reaction of the o-ethynylphenyl isothiocyanate 1A with sodium
methoxide 8a afforded the methyl thiocarbamate 9a in 96% yield.
Not only the primary alkoxide, ethyl 8b and benzyl alkoxide 8c, but
also a secondary alkoxide, iso-propoxide 8d, reacted with the o-
ethynylphenyl isothiocyanate 1A to afford the corresponding

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H. Sashida et al. / Tetrahedron 69 (2013) 6478e6487
Scheme 1. .
Fig. 1. An ORTEP drawing of 7Ae with thermal ellipsoid plot (50% probability).
thiourethanes 9 in high yields. In contrast, the tert-butyl thiour-
ethane derivative 9e could not be obtained in a stable state from 1A
and the tertiary alkoxide 8e under the same conditions. It is too
unstable to be isolated, and decomposed during the purification.
Furthermore, the isothiocyanate 1A did not react with sodium
phenoxide, and the starting material 1A was recovered.
The treatment of the isolated thiourethanes 9a with
1.3 mol equiv of iodine in the presence of Cs2CO3 in dry DCE
resulted in the 6-exo-dig mode ring-closure to give the desired
product, (E)-2-methoxybenzo[d][1,3]thiazine 10a, in 46% yield. In
this iodocyclization, no 7-endo-dig mode cyclization reaction
products were obtained; the 11-membered disulfide 11 was also
produced in 36% yield. The use of other thiourethanes 9 was also
performed. The reaction of ethyl thiourethane 9b with I2 under
similar conditions gave the (E)-3,1-thiazines 10b and the disulfide
11 in 48 and 39% yields, respectively. Both the 2-benzyloxy 10c and
2-iso-propyloxy-3,1-thiazines 10d were also isolated in moderate
yields by the reaction of the corresponding thiourethanes 9 with I2
via the 6-exo-dig mode cyclization, together with the disulfide 11 in
yields ranging from 30 to 40%. Regrettably, the treatment of the
obtained crude tert-butyl thiourethane derivative 9e with I2 under
the same conditions gave a complex mixture without any charac-
terized product, even the disulfide 11. The formation of the disulfide
Fig. 2. An ORTEP drawing of 3Da-Z.
11 may be explained by the hydrolysis and self-condensation of the
cyclization products 10 including the oxidation of the thiol moiety.
Both the adducts 9 and cyclization products 10 were relatively
unstable, and gradually decomposed at room temperature.
2.7. Cross-coupling reaction of (4E)-4-(1-iodomethylidene)be
nzo[d][1,3]thiazines
The iodomethylidenebenzothiazine 3Aa can be deiodinated to
give 12 by treatment with HCOOH/Et3N in the presence of
PdCl2(PPh3)2; compound 12 has been previously synthesized.20 The
3Aa was transformed into the phenylated 4-(methylidene)benzo-
thiazine 13 by the palladium-catalyzed Suzuki coupling reaction
with phenylboronic acid through the CeC bond formation in 73%

H. Sashida et al. / Tetrahedron 69 (2013) 6478e6487
6483
recorded on a Horiba FT-720 spectrophotometer. MS and HRMS
spectra were recorded on a JEOL JMS-DX300 instrument. 1H NMR
spectra were recorded on a JEOL ECP-500 (500 MHz) spectrometer
using TMS as internal standard in CDCl3 and J values are given in
hertz. 13C NMR spectra were recorded on a JEOL ECP-500 (125 Hz)
spectrometer in CDCl3.
4.2. Starting materials
The starting materials, o-ethynylphenyl isothiocyanates 1A, 1B,
1C, and 1D were prepared by the literature method.22
4.3. Reaction of 2-ethynylphenyl isothiocyanate with dieth-
ylamine and I2
A mixture of 2-ethynylphenyl isothiocyanate 1A (215 mg,1 mmol)
and diethylamine 2a (80 mg, 1.1 mmol) in dry DCE (2 mL) was stirred
at room temperature under argon atmosphere for 10 min, and then I2
(330 mg, 1.3 mmol) and Cs2CO3 (489 mg, 1.5 mmol) were added. The
mixture was heated at 65 ꢀC with stirring for 3e4 h, and then diluted
with CHCl3 (10 mL). The organic layer was washed with 2% Na2S2O3
aq (15 mLꢁ3), water (15 mLꢁ2), dried over anhydrous Na2SO4, and
evaporated in vacuo. The obtained residue was chromatographed on
silica gel using hexane/CHCl3 (1:1) as an eluent to give pure (4E)-4-
(iodomethylidene)-1,3-benzothiazine.
Scheme 2.
yield. The Sonogashira reaction with phenylacetylene also pro-
ceeded to give the alkynylated benzothiazine 14 in 90%
yield (Scheme 3).
4.3.1. (4E)-2-(N,N-Diethylamino)-4-(1-iodopentylidene)-4H-benzo[d]
[1,3]thiazine 3Aa. Yield: 343 mg (83%). Yellow oil. IR (KBr, neat): 1556
(C]N) cmꢂ1. 1H NMR (500 MHz, CDCl3)
d
¼0.97,1.36e1.45,1.57e1.66,
3.05 (3H, t, J¼7.3 Hz, 2H, m, 2H, m, 2H, t, J¼7.4 Hz, n-Bu), 1.22, 3.60
(6H, t, J¼7.1 Hz, 4H, q, J¼7.1 Hz, NEt2), 7.02, 7.09, 7.27, 7.77 (1H, ddd,
J¼7.7, 7.6, 1.0 Hz, 1H, dd, J¼7.8, 1.0 Hz, 1H, ddd, J¼7.8, 7.6, 1.5 Hz, 1H,
dd, J¼7.7, 1.5 Hz, PheH). 13C NMR (125 MHz, CDCl3)
¼14.02 (q),
d
14.04 (q), 21.7 (t), 31.3 (t), 43.7 (t), 44.0 (t), 104.3 (s), 121.5 (d), 124.3
(s), 124.5 (d), 125.0 (s), 127.9 (d), 129.2 (d), 147.4 (s), 153.6 (s). MS (EI):
m/z (relative intensity, %) 414 (Mþ, 100), 385 (26), 318 (24), 287 (72),
245 (44), 135 (48). HRMS (EI) m/z Mþ calcd for C17H23N2IS: 414.0627;
found: 414.0622.
4.3.2. 1,1-Diethyl-3-[2-(hex-1-ynyl)phenyl]thiourea 4. o-Ethynylphen
yl isothiocyanate 1A was treated with diethylamine 2a in dry CH2Cl2
instead of dry DCE without I2 and worked up as described for the
preparation of 3Aa to give 4. Yield: 262 mg (91%). Yellow oil. IR (KBr,
neat): 3363 (NH), 2224 (C^C), 1583 (C]S) cmꢂ1. 1H NMR (500 MHz,
CDCl3)
d
¼0.94, 1.41e1.52, 1.55e1.64, 2.44 (3H, t, J¼7.3 Hz, 2H, m, 2H,
m, 2H, t, J¼7.1 Hz, n-Bu), 1.35, 3.80 (6H, t, J¼7.1 Hz, 4H, q, J¼7.1 Hz,
NEt2), 7.02, 7.27, 7.37, 8.43 (1H, ddd, J¼7.7, 7.5, 1.0 Hz, 1H, ddd, J¼8.3,
7.5,1.6 Hz,1H, dd, J¼7.7, 1.6 Hz, 1H, dd, J¼8.3,1.0 Hz, PheH), 7.72e7.83
Scheme 3.
(1H, br, NH). 13C NMR (125 MHz, CDCl3)
d¼12.6 (q), 13.6 (q), 19.4 (t),
3. Conclusion
22.0 (t), 30.8 (t), 45.5 (t), 76.7 (s), 97.3 (s),115.4 (s),122.7 (d),123.5 (d),
127.7 (d), 131.8 (d), 140.7 (s), 179.0 (s). MS (EI): m/z (relative intensity,
%) 288 (Mþ, 100), 213 (36), 186 (21), 116 (49), 88 (17). HRMS (EI) m/z
The one-pot tandem additioneiodocyclization of the o-ethy-
nylphenyl isothiocyanates with both secondary and primary
amines for the efficient preparation of the 4-(1-iodomethylidene)
benzothiazines via the 6-exo-dig mode ring-closure reaction
smoothly proceeded; the intermediates, thioureas, could be iso-
lated and transformed into the benzothiazines. The obtained ben-
zothiazines were converted to the more functionalized derivatives
via the palladium cross-coupling reactions.
M
þ calcd for C17H24N2S: 288.1660; found: 288.1664.
4.3.3. N-[(Diethylamino)(diethylaminothio)methylidene]-2-(hex-1-
ynyl)aniline 5. o-Ethynylphenyl isocyanate 1A was treated with
diethylamine 2a (2.2 mmol) in dry CH3CN instead of dry DCE and
worked up as described for the preparation of 3Aa to give 5.
Yield: 310 mg (86%). Yellow oil. IR (KBr, neat): 2027 (C^C), 1610
(C]N) cmꢂ1
.
1H NMR (500 MHz, CDCl3)
d
¼0.87e0.94, 1.21,
4. Experimental section
4.1. General
1.41e1.49, 1.49e1.58, 2.37, 2.56, 3.48 (9H, m, 6H, t, J¼7.0 Hz, 2H, m,
2H, m, 2H, t, J¼7.0 Hz, 4H, q, J¼7.0 Hz, 4H, q, J¼7.0 Hz, n-Bu,
NEt2ꢁ2), 6.71e6.77, 7.08, 7.28 (2H, m, 1H, ddd, J¼7.9, 7.6, 1.5 Hz, 1H,
dd, J¼7.9, 1.3 Hz, PheH). 13C NMR (125 MHz, CDCl3)
¼13.4 (q),
d
Melting points were measured on a Yanagimoto micro melting
point hot stage apparatus and are uncorrected. IR spectra were
13.71 (q), 13.74 (q), 19.5 (t), 22.0 (t), 31.1 (t), 43.8 (t), 51.0 (t), 80.0 (s),
92.4 (s), 114.9 (s), 120.0 (d), 120.8 (d), 127.6 (d), 132.2 (d), 152.6 (s),

6484
H. Sashida et al. / Tetrahedron 69 (2013) 6478e6487
156.5 (s). MS (FAB): m/z (relative intensity, %) 360 (MHþ, 5), 289
(45), 255 (100), 135 (51), 116 (46), 88 (21). HRMS (FAB) m/z MHþ
calcd for C21H34N3S: 360.24730; found: 360.2586.
d
¼1.22, 3.62 (6H, t, J¼7.1 Hz, 4H, q, J¼7.1 Hz, NEt2), 1.55 (9H, s, t-
Bu), 6.99, 7.07, 7.24, 7.58 (1H, ddd, J¼7.7, 7.4, 1.3 Hz, 1H, dd, J¼8.0,
1.3 Hz, 1H, ddd, J¼8.0, 7.4, 1.5 Hz, 1H, dd, J¼7.7, 1.5 Hz, PheH). 13C
NMR (125 MHz, CDCl3)
d
¼14.2 (q), 33.2 (q), 41.7 (s), 43.8 (t), 121.6
4.4. Typical procedure for preparation of (4E)-2-amino-4-
(1-iodomethylidene)benzo[d][1,3]thiazines
(s), 121.7 (d), 124.2 (d), 125.1 (s), 128.6 (s), 129.0 (d), 129.6 (d), 147.2
(s), 153.9 (s). MS (EI): m/z (relative intensity, %) 414 (Mþ, 100), 399
(73), 287 (18), 83 (31). HRMS (EI) m/z Mþ calcd for C17H23N2IS:
414.0627; found: 414.0610.
o-Ethynylphenyl isothiocyanate 1 was treated with the appro-
priate secondary amine 2 and worked up as described for the
preparation of 3Aa to give 3.
4.5. Typical procedure for preparation of (4E)-2-imino-4-(1-
iodomethylidene)benzo[d][1,3]thiazines
4.4.1. (4E)-4-(1-Iodopentylidene)-2-(piperidin-1-yl)-4H-benzo[d]
[1,3]thiazine 3Ab. Yield: 379 mg (89%). Yellow oil. IR (KBr, neat):
o-Ethynylphenyl isocyanate 1 was treated with the appropriate
primary amine 6 and worked up as described for the preparation of
3Aa to give 7.
1549 (C]N) cmꢂ1
.
1H NMR (500 MHz, CDCl3)
d
¼0.97, 1.36e1.45,
1.57e1.72, 3.04, 3.71e3.79 (3H, t, J¼7.3 Hz, 2H, m, 4H, m, 2H, t,
J¼7.4 Hz, 4H, m, n-Bu, piperidineeH), 7.04, 7.10, 7.27, 7.77 (1H, ddd,
J¼7.8, 7.2, 1.2 Hz, 1H, dd, J¼8.0, 1.2 Hz, 1H, ddd, J¼8.0, 7.2, 1.5 Hz, 1H,
4.5.1. (2Z,4E)-2-tert-Butylimino-4-(1-iodopentylidene)-4H-1,2-
dd, J¼7.8, 1.5 Hz, PheH). 13C NMR (125 MHz, CDCl3)
d¼14.1 (q), 21.7
dihydrobenzo[d][1,3]thiazine 7Aa. Yield: 323 mg (78%). Colorless oil.
(t), 24.9 (t), 25.9 (t), 31.2 (t), 44.0 (t), 48.1 (t), 104.6 (s), 122.0 (d),
124.57 (s), 124.58 (d), 125.0 (s), 127.9 (d), 129.2 (d), 147.1 (s), 154.8
(s). MS (EI): m/z (relative intensity, %) 426 (Mþ, 100), 383 (13), 299
(20), 216 (30). HRMS (EI) m/z Mþ calcd for C18H23N2IS: 426.0627;
found: 426.0627.
IR (KBr, neat): 3400 (NH), 1615 (C]N) cmꢂ1 1H NMR (500 MHz,
.
CDCl3)
d
¼0.97, 1.34e1.43, 1.55e1.63, 2.98 (3H, t, J¼7.3 Hz, 2H, m, 2H,
m, 2H, t, J¼7.5 Hz, n-Bu), 1.48 (9H, s, t-Bu), 4.25e4.53 (1H, br, NH),
7.07, 7.15, 7.29, 7.79 (1H, ddd, J¼7.8, 7.3, 1.0 Hz, 1H, dd, J¼8.0, 1.0 Hz,
1H, ddd, J¼8.0, 7.3, 1.3 Hz, 1H, dd, J¼7.8, 1.3 Hz, PheH). 13C NMR
(125 MHz, CDCl3)
d¼14.0 (q), 21.6 (t), 29.4 (q), 31.2 (t), 44.0 (t), 53.9
4.4.2. (4E)-4-(1-Iodopentylidene)-2-(pyrrolidin-1-yl)-4H-benzo[d]
[1,3]thiazine 3Ac. Yield: 363 mg (88%). Yellow oil. IR (KBr, neat):
(s), 103.9 (s), 122.3 (d), 124.6 (s), 124.8 (d), 125.4 (s), 128.1 (d), 129.2
(d), 146.9 (s), 150.0 (s). MS (EI): m/z (relative intensity, %) 414 (Mþ,
50), 325 (91), 299 (100), 2561 (73), 224 (76). HRMS (EI) m/z Mþ calcd
for C17H23N2IS: 414.0627; found: 414.0628.
1560 (C]N) cmꢂ1
.
1H NMR (500 MHz, CDCl3)
d¼0.98, 1.35e1.45,
1.57e1.65, 3.04 (3H, q, J¼7.3 Hz, 2H, m, 2H, m, 2H, t, J¼7.4 Hz, n-Bu),
1.90e2.01, 3.57e3.70 (4H, m, 4H, m, pyrrolidineeH), 7.01, 7.10, 7.27,
7.76 (1H, dd, J¼7.8, 7.3 Hz, 1H, d, J¼8.1, 7.3 Hz, 1H, ddd, J¼8.1, 7.3,
1.2 Hz, 1H, dd, J¼7.8, 1.2 Hz, PheH). 13C NMR (125 MHz, CDCl3)
4.5.2. (2Z,4E)-2-n-Butylimino-4-(1-iodopentylidene)-4H-1,2-
dihydrobenzo[d][1,3]thiazine 7Ab. Yield: 273 mg (66%). Yellow oil. IR
(KBr, neat): 3406 (NH), 1610 (C]N) cmꢂ1. 1H NMR (500 MHz, CDCl3)
d
¼14.1 (q), 21.7 (t), 25.0 (t), 31.3 (t), 44.1 (t), 48.1 (t), 103.6 (s), 121.5
(d), 124.0 (s), 124.5 (d), 124.8 (s), 128.2 (d), 129.4 (d), 147.4 (s), 152.5
(s). MS (EI): m/z (relative intensity, %) 412 (Mþ, 100), 369 (23), 285
(24), 242 (32), 216 (12). HRMS (EI) m/z Mþ calcd for C17H21N2IS:
412.0470; found: 412.0472.
d
¼0.95, 0.97, 1.32e1.49, 1.53e1.64, 2.98, 3.51 (3H, t, J¼7.2 Hz, 3H, t,
J¼7.2 Hz, 4H, m, 4H, m, 2H, t, J¼7.5 Hz, 2H, t, J¼7.2 Hz, n-Buꢁ2),
4.34e4.84 (1H, br, NH), 7.07, 7.13, 7.30, 7.78 (1H, ddd, J¼7.7, 7.3, 1.3 Hz,
1H, dd, J¼8.0, 1.3 Hz, 1H, ddd, J¼8.0, 7.3, 1.4 Hz, 1H, dd, J¼7.7, 1.4 Hz,
PheH). 13C NMR (125 MHz, CDCl3)
d¼13.8 (q), 14.0 (q), 20.1 (t), 21.6
4.4.3. (4E)-4-(1-Iodopentylidene)-2-morpholinyl-4H-benzo[d][1,3]
thiazine 3Ad. Yield: 407 mg (95%). Yellow oil. IR (KBr, neat): 1552
(t), 31.3 (t), 31.7 (t), 42.5 (t), 44.0 (t), 104.2 (s), 122.3 (d), 124.67 (d),
124.72 (s), 124.9 (d), 128.3 (d), 129.4 (s), 146.8 (s), 152.8 (s). MS (EI):
m/z (relative intensity, %) 414 (Mþ, 100), 371 (15), 287 (84), 201 (14),
115 (6). HRMS (EI) m/z Mþ calcd for C17H23N2IS: 414.0627; found:
414.0625.
(C]N) cmꢂ1
.
1H NMR (500 MHz, CDCl3)
d
¼0.97, 1.35e1.46,
1.57e1.65, 3.03 (3H, t, J¼7.3 Hz, 2H, m, 2H, m, 2H, t, J¼7.4 Hz, n-Bu),
3.72e3.79 (8H, br, morpholineeH), 7.09, 7.11, 7.30, 7.79 (1H, ddd,
J¼7.8, 7.4, 1.3 Hz, 1H, dd, J¼8.0, 1.3 Hz, 1H, ddd, J¼8.0, 7.4, 1.5 Hz, 1H,
dd, J¼7.8, 1.5 Hz, PheH). 13C NMR (125 MHz, CDCl3)
d¼14.1 (q), 21.7
4.5.3. (2Z,4E)-2-Cyclohexylimino-4-(1-iodopentylidene)-4H-1,2-
dihydrobenzo[d][1,3]thiazine 7Ac. Yield: 356 mg (81%). Yellow oil. IR
(KBr, neat): 3435 (NH), 1606 (C]N) cmꢂ1. 1H NMR (500 MHz, CDCl3)
(t), 31.3 (t), 40.0 (t), 47.4 (t), 66.6 (t), 105.2 (s), 122.7 (d), 124.1 (s),
124.6 (s), 124.7 (d), 128.1 (d), 129.4 (d), 146.4 (s), 155.2 (s). MS (EI):
m/z (relative intensity, %) 428 (Mþ, 100), 385 (32), 301 (41), 258
(28). HRMS (EI) m/z Mþ calcd for C17H21ON2IS: 428.0419; found:
428.0418.
d
¼0.97, 1.12e1.26, 1.35e1.46, 1.54e1.66, 1.68e1.77, 2.02e2.11, 2.99,
3.93e4.03 (3H, t, J¼7.3 Hz, 3H, m, 4H, m, 3H, m, 2H, m, 2H, m, 2H, t,
J¼7.4 Hz, 1H, m, n-Bu, cyclohexyleH), 4.42e4.67 (1H, br, NH), 7.06,
7.12, 7.28, 7.78 (1H, ddd, J¼8.0, 7.3, 1.3 Hz, 1H, dd, J¼8.0, 1.0 Hz, 1H,
ddd, J¼7.8, 7.3, 1.0 Hz, 1H, dd, J¼7.8, 1.3 Hz, PheH). 13C NMR
4.4.4. (4E)-4-(1-Iodopentylidene)-2-(N-methyl-N-phenylamino)-4H-
benzo[d][1,3]thiazine 3Ae. Yield: 408 mg (91%). Yellow oil. IR (KBr,
(125 MHz, CDCl3)
d¼14.0 (q), 21.6 (t), 24.8 (t), 25.6 (t), 31.3 (t), 33.4 (t),
neat): 1548 (C]N) cmꢂ1
.
1H NMR (500 MHz, CDCl3)
d
¼0.85,
44.0 (t), 51.3 (d), 104.1 (s), 122.2 (d), 124.7 (d), 124.9 (s), 128.2 (d),
129.3 (d), 140.8 (s), 146.9 (s), 151.8 (s). MS (EI): m/z (relative intensity,
%) 440 (Mþ, 89), 358 (17), 313 (100), 231 (74),188 (22). HRMS (EI) m/z
Mþ calcd for C19H25N2IS: 440.0783; found: 440.0782.
1.18e1.28, 1.43e1.51, 2.77 (3H, t, J¼7.4 Hz, 2H, m, 2H, m, 2H, t,
J¼7.5 Hz, n-Bu), 3.54 (3H, s, NMe), 7.08, 7.19e7.27, 7.29e7.36,
7.37e7.43, 7.77 (1H, ddd, J¼7.7, 7.5, 1.2 Hz, 3H, m, 2H, m, 2H, m, 1H,
dd, J¼7.7, 1.4 Hz, PheH). 13C NMR (125 MHz, CDCl3)
¼13.9 (q), 21.5
d
(t), 30.9 (t), 39.9 (q), 43.6 (t), 104.5 (s), 122.5 (d), 124.8 (s), 124.8 (d),
125.5 (s), 127.5 (d), 127.7 (d), 128.0 (d), 129.3 (d), 144.5 (s), 146.7 (s),
154.5 (s). MS (EI): m/z (relative intensity, %) 448 (Mþ, 100), 405 (27),
321 (34), 278 (45), 106 (23), 83 (15). HRMS (EI) m/z Mþ calcd for
C20H21N2IS: 448.0470; found: 448.0471.
4.5.4. (2Z,4E)-2-Benzylimino-4-(1-iodopentylidene)-4H-1,2-
dihydrobenzo[d][1,3]thiazine 7Ad. Yield: 363 mg (81%). Yellow oil. IR
(KBr, neat): 3498 (NH), 1610 (C]N) cmꢂ1. 1H NMR (500 MHz, CDCl3)
d
¼0.95, 1.33e1.42, 1.54e1.62, 2.96 (3H, t, J¼7.3 Hz, 2H, m, 2H, m, 2H,
t, J¼7.5 Hz, n-Bu), 4.43e5.17 (1H, br, NH), 4.69 (2H, s, NCH2), 7.09,
7.16, 7.26e7.39, 7.81 (1H, ddd, J¼7.8, 7.4, 1.3 Hz, 1H, dd, J¼8.0, 1.0 Hz,
4.4.5. (4E)-2-(N,N-Diethylamino)-4-(1-iodo-2,2-dimethylpropyli-
dene)-4H-benzo[d][1,3]thiazine 3Ba. Yield: 373 mg (90%). Yellow
oil. IR (KBr, neat): 15,681 (C]N) cmꢂ1. 1H NMR (500 MHz, CDCl3)
6H, m,1H, dd, J¼7.8, 1.3 Hz, PheH). 13C NMR (125 MHz, CDCl3)
¼14.0
d
(q), 21.6 (t), 31.2 (t), 44.0 (t), 46.8 (t), 104.5 (s), 122.6 (d), 124.5 (s),
124.8 (d), 125.0 (s), 127.7 (d), 128.1 (d), 128.4 (d), 128.7 (d), 129.4 (d),

H. Sashida et al. / Tetrahedron 69 (2013) 6478e6487
6485
138.1 (s), 146.6 (s), 152.5 (s). MS (EI): m/z (relative intensity, %) 448
(Mþ, 100), 405 (10), 321 (8), 216 (14), 91 (23). HRMS (EI) m/z Mþ calcd
for C20H21N2IS: 448.0470; found: 448.0463.
yellow prisms, mp 139e140 ꢀC (from CHCl3/hexane). IR (KBr, tab):
3413 (NH),1614 (C]N) cmꢂ1. 1H NMR (500 MHz, CDCl3)
d
¼1.41 (9H,
s, t-Bu), 4.20 (1H, br s, NH), 7.13, 7.19, 7.32e7.42, 8.03 (1H, ddd,
J¼7.8, 7.2, 1.4 Hz, 1H, dd, J¼8.0, 1.4 Hz, 6H, m, 1H, dd, J¼7.8, 1.5 Hz,
4.5.5. (2Z,4E)-4-(1-Iodopentylidene)-2-phenylimino-4H-1,2-
dihydrobenzo[d][1,3]thiazine 7Ae. Yield: 361 mg (84%). Reddish
prisms, mp 145e146 ꢀC (from benzene/hexane). IR (KBr, tab): 3437
PheH). 13C NMR (125 MHz, CDCl3)
d
¼29.3 (q), 53.9 (s), 93.7 (s),
122.5 (d), 123.6 (s), 125.4 (d), 127.9 (d), 128.3 (d), 128.7 (d), 129.3 (s),
129.4 (d), 129.9 (d), 144.1 (s), 147.2 (s), 149.7 (s). MS (EI): m/z (rel-
ative intensity, %) 434 (Mþ, 100), 378 (9), 344 (15), 307 (30), 251
(83), 218 (42), 190 (15). HRMS (EI) m/z Mþ calcd for C19H19N2IS:
434.0314; found: 434.0306.
(NH), 1630 (C]N) cmꢂ1
.
1H NMR (500 MHz, CDCl3)
d¼0.95,
1.32e1.42, 1.55e1.63, 2.96 (3H, t, J¼7.3 Hz, 2H, m, 2H, m, 2H, t,
J¼7.5 Hz, n-Bu), 7.04e7.14, 7.26e7.36, 7.38e7.46, 7.80 (3H, m, 4H, m,
1H, m, 1H, dd, J¼7.8 Hz, PheH), 7.38e7.46 (1H, br, NH). 13C NMR
(125 MHz, CDCl3)
d
¼14.0 (q), 21.6 (t), 31.2 (t), 44.1 (t), 105.9 (s), 121.0
4.6.4. (2Z,4E)-2-(N-tert-Butylimino)-4-(iodobenzylidene)-4H-1,2-
dihydrobenzo[d][1,3]thiazine 7Da-Z. Yield: 334 mg (77%). Colorless
prisms, mp 177e179 ꢀC (from CHCl3/hexane). IR (KBr, tab): 3394
(d), 122.8 (d), 122.9 (d), 123.8 (s), 123.9 (d), 125.1 (s), 128.5 (d), 129.0
(d), 129.5 (d), 141.8 (s), 143.8 (s), 150.6 (s). MS (EI): m/z (relative in-
tensity, %) 434 (Mþ, 100), 391 (13), 307 (43), 264 (24), 231 (16), 162
(16). HRMS (EI) m/z Mþ calcd for C19H19N2IS: 434.0314; found:
434.0312. Anal. Calcd for C19H19N2IS: C, 52.53; H, 4.38; N, 6.45.
Found: C, 52.68; H, 4.37; N, 6.43.
(NH), 1616 (C]N) cmꢂ1. 1H NMR (500 MHz, CDCl3)
d¼1.53 (9H, s, t-
Bu), 4.32e4.82 (1H, br, NH), 6.60, 6.63, 7.13, 7.15e7.23, 7.23e7.27 (1H,
ddd, J¼7.8, 6.8, 1.4 Hz, 1H, dd, J¼7.8, 1.7 Hz, 1H, ddd, J¼7.8, 6.8, 1.7 Hz,
4H, m, 2H, m, PheH). 13C NMR (125 MHz, CDCl3)
d
¼29.5 (q), 54.2 (s),
103.4 (s), 121.4 (s), 122.6 (d), 125.4 (d), 128.2 (d), 128.3 (d), 128.6 (d),
129.2 (d),130.2 (d),133.9 (s),143.5 (s),147.7 (s),150.5 (s). MS (EI): m/z
(relative intensity, %) 434 (Mþ, 100), 378 (9), 307 (31), 251 (82), 218
(41), 190 (12), 57 (8). HRMS (EI) m/z Mþ calcd for C19H19N2IS:
434.0314; found: 434.0310.
4.5.6. (2Z,4E)-2-tert-Butylimino-4-(1-iodo-2,2-dimethylpropylidene)-
4H-1,2-dihydrobenzo[d][1,3]thiazine 7Ba. Yield: 215 mg (52%). Yellow
oil. IR (KBr, neat): 3396 (NH), 1612 (C]N) cmꢂ1. 1H NMR (500 MHz,
CDCl3)
d
¼1.48 (9H, s, t-Bu), 1.51 (9H, s, t-Bu), 4.34e4.47 (1H, br, NH),
7.04, 7.12, 7.25, 7.59 (1H, ddd, J¼7.8, 7.3, 1.4 Hz, 1H, dd, J¼7.8, 1.2 Hz,
1H, ddd, J¼7.9, 7.3, 1.2 Hz, 1H, dd, J¼7.9, 1.4 Hz, PheH). 13C NMR
4.7. Typical procedure for addition of 2-ethynylphenyl iso-
thiocyanate with the alkoxide: formation of thiourethane
(125 MHz, CDCl3)
d¼29.5 (q), 32.9 (q), 41.8 (s), 54.0 (s),121.0 (s),122.4
(d), 124.5 (d), 125.5 (s), 128.8 (s), 128.9 (d), 129.9 (d), 146.9 (s), 150.1
(s). MS (EI): m/z (relative intensity, %) 414 (Mþ, 100), 399 (54), 287
(19), 231 (40), 57 (11). HRMS (EI) m/z Mþ calcd for C17H23N2IS:
414.0627; found: 414.0626.
To a solution of alkoxide (1.5 mmol), freshly prepared from al-
cohol (5 mmol) and 60% NaH (60 mg, 1.5 mmol) in dry THF (2 mL),
was slowly added to a solution of o-ethynylphenyl isothiocyanate
3Aa (215 mg,1 mmol) in dry THF (2 mL) under an argon atmosphere.
The reaction mixture was stirred at room temperature for 1 h, and
then quenched by the addition of brine (50 mL). The resulting
mixture was extracted with benzene (50 mLꢁ3). The organic layer
was washed with brine (10 mLꢁ2), dried (Na2SO4), and evaporated
in vacuo. The obtained residue was chromatographed on silica gel
using hexane/CHCl3 (1:2) as an eluent to give pure thiourethane.
4.6. Reaction of 2-(phenylethynyl)phenyl isothiocyanate with
amine and I2
o-(Phenylethynyl)phenyl isothiocyanate 1D was treated with
diethylamine 2a or tert-butylamine 6a and worked up as described
for the preparation of 3Aa to give 3Da or 7Da. All operations (re-
action and purification) for 3Da-E and 7Da-E were performed in
a dark room.
4.7.1. Methyl 2-(hex-1-ynyl)phenylcarbamothioate 9a. Yield: 237 mg
(96%). Yellow oil. IR (KBr, neat): 3361 (NH), 2224 (C^C) cmꢂ1 1H
.
4.6.1. (4E)-2-(N,N-Diethylamino)-4-(1-iodobenzylidene)-4H-benzo[d]
[1,3]thiazine 3Da-E. Yield: 391 mg (90%). Pale yellow prisms, mp
185e186 ꢀC (from CHCl3/hexane). IR (KBr, tab): 1545 (C]N) cmꢂ1. 1H
NMR (500 MHz)
d
¼0.97, 1.47e1.56, 1.60e1.68, 2.50 (3H, t, J¼7.3 Hz,
2H, m, 2H, m, 2H, t, J¼7.0 Hz, n-Bu), 4.14 (3H, br s, OMe), 7.05, 7.26,
7.37, 7.45e8.05 (1H, dd, J¼7.7, 7.5 Hz, 1H, dd, J¼8.0, 7.7 Hz, 1H, dd,
J¼8.0, 1.4 Hz, 1H, m, PheH), 8.60e9.10 (1H, br, NH). 13C NMR
NMR (500 MHz, CDCl3)
d
¼1.09, 3.42 (6H, t, J¼7.0 Hz, 4H, q, J¼7.0 Hz,
NEt2), 7.09, 7.13, 7.29e7.35, 7.36e7.41, 8.01 (1H, ddd, J¼7.6, 7.4, 1.2 Hz,
(125 MHz)
d
¼13.6 (q), 19.3 (t), 22.1 (t), 30.7 (t), 57.2 (q), 75.6 (s), 98.7
1H, dd, J¼8.1, 1.0 Hz, 4H, m, 2H, m, 1H, dd, J¼7.8, 1.1 Hz, PheH). 13C
(s), 114.6 (s), 120.4 (d), 124.2 (d), 128.3 (d), 131.8 (d), 138.2 (s), 189.2
(s). MS m/z (relative intensity, %): 247 (Mþ, 42), 205 (56), 190 (100),
172 (84), 130 (71), 75 (65). HRMS m/z calcd for C14H17NOS: 247.1031;
found: 247.1031.
NMR (125 MHz, CDCl3)
d
¼13.7 (q), 43.6 (t), 94.2 (s), 121.7 (d), 123.3
(s), 124.9 (d), 127.5 (d), 128.3 (d), 128.5 (d), 128.8 (s), 129.1 (d), 129.9
(d), 144.4 (s), 147.7 (s), 153.4 (s). MS (EI): m/z (relative intensity, %)
434 (Mþ, 100), 405 (10), 307 (26), 236 (20), 72 (14). HRMS (EI) m/z
M
þ calcd for C19H19N2IS: 434.0314; found: 434.0306.
4.7.2. Ethyl 2-(hex-1-ynyl)phenylcarbamothioate 9b. Yield: 243 mg
(93%). Yellow oil. IR (KBr, neat): 3360 (NH), 2224 (C^C) cmꢂ1. 1H
4.6.2. (4E)-2-(N,N-Diethylamino)-4-(1-iodobenzylidene)-4H-benzo
[d][1,3]thiazine 3Da-Z. Yield: 334 mg (77%). Pale yellow prisms,
mp 206e208 ꢀC (from CHCl3/hexane). IR (KBr, tab): 1566, 1549
NMR (500 MHz)
d
¼0.97, 1.48e1.55, 1.60e1.68, 2.50 (3H, t, J¼7.3 Hz,
2H, m, 2H, m, 2H, t, J¼7.0 Hz, n-Bu), 1.44, 4.57e4.71 (3H, t, J¼7.0 Hz,
2H, m, OEt), 7.04, 7.26, 7.38, 7.65e8.00 (1H, dd, J¼7.7, 7.4 Hz, 1H, dd,
J¼7.4, 6.8 Hz, 1H, dd, J¼7.7, 1.4 Hz, 1H, m, PheH), 8.75e9.05 (1H, br,
(C]N) cmꢂ1
.
1H NMR (500 MHz, CDCl3)
d
¼1.29, 3.68 (6H, t,
J¼7.1 Hz, 4H, q, J¼7.1 Hz, NEt2), 6.51e6.57, 6.61, 7.10, 7.17e7.26 (1H,
NH). 13C NMR (125 MHz)
d
¼13.6 (q), 14.1 (t), 22.1 (t), 30.7 (t), 68.8
m, 1H, dd, J¼7.8, 0.9 Hz, 2H, d, J¼3.7 Hz, 5H, m, PheH). 13C NMR
(t), 75.7 (s), 98.7 (s), 114.4 (s), 120.4 (d), 124.1 (d), 128.3 (d), 131.8 (d),
138.3 (s), 188.0 (s). MS m/z (relative intensity, %): 261 (Mþ, 24), 232
(80), 219 (21), 190 (100), 172 (63), 130 (77), 128 (38). HRMS m/z
calcd for C15H19NOS: 261.1187; found: 261.1194.
(125 MHz, CDCl3)
d
¼14.0 (q), 43.7 (t), 102.9 (s), 120.9 (s), 121.7 (d),
125.2 (d), 128.2 (d), 128.3 (d, two carbon), 129.2 (d), 130.2 (d), 133.8
(s), 143.9 (s), 148.3 (s), 154.0 (s). MS (EI): m/z (relative intensity, %)
434 (Mþ, 100), 405 (9), 307 (24), 263 (10), 236 (15). HRMS (EI) m/z
Mþ calcd for C19H19N2IS: 434.0314; found: 434.0316.
4.7.3. Benzyl 2-(hex-1-ynyl)phenylcarbamothioate 9c. Yield: 304 mg
(94%). Yellow oil. IR (KBr, neat): 3356 (NH), 2225 (C^C) cmꢂ1 1H
.
4.6.3. (2Z,4E)-2-(N-tert-Butylimino)-4-(1-iodobenzylidene)-4H-1,2-
dihydrobenzo[d][1,3]thiazine 7Da-E. Yield: 339 mg (78%). Pale
NMR (500 MHz)
d
¼0.84e1.02, 1.43e1.68, 2.48 (3H, br, 4H, br, 2H, t,
J¼6.9 Hz, n-Bu), 5.55e5.70 (2H, br, CH2Ph), 6.97e7.08, 7.10e7.30,

6486
H. Sashida et al. / Tetrahedron 69 (2013) 6478e6487
7.33e7.46, 7.48e7.90 (1H, br, 1H, br, 6H, m, 1H, m, PheH), 8.50e9.13
(1H, br, NH). 13C NMR (125 MHz)
(Mþ, 52), 322 (19), 266 (44), 161 (13), 91 (100). HRMS m/z calcd for
C20H20NOIS: 449.0310; found: 449.0314.
d¼13.6 (q), 19.3 (t), 22.1 (t), 30.6 (t),
60.7 (t), 75.6 (s), 98.8 (s),120.5 (d),124.2 (d),128.2 (d),128.4 (d),128.5
(d), 128.6 (d), 131.8 (d), 135.1 (s), 135.3 (s), 138.2 (s), 187.9 (s). MS m/z
(relative intensity, %): 323 (Mþ, 38), 232 (38), 199 (74), 156 (58), 130
(69), 91 (100). HRMS m/z calcd for C20H21NOS: 323.1344; found:
323.1343.
4.8.4. (4E)-4-(1-Iodopentylidene)-2-iso-propoxy-4H-benzo[d][1,3]thia-
zine 10d. Yield: 156 mg (39%). Yellow oil. IR (KBr): 1614 (C]N) cmꢂ1
.
1H NMR (500 MHz)
d
¼0.97, 1.34e1.44, 1.55e1.64, 3.01 (3H, t, J¼7.2 Hz,
2H, m, 2H, m, 2H, t, J¼7.4 Hz, n-Bu), 1.37, 5.42e5.52 (6H, d, J¼6.2 Hz,
1H, m, i-Pro), 7.13e7.21, 7.33, 7.87 (2H, m, 1H, ddd, J¼8.0, 7.8,1.6 Hz, 1H,
4.7.4. iso-Propyl 2-(hex-1-ynyl)phenylcarbamothioate 9d. Yield: 23
dd, J¼8.3, 1.7 Hz, PheH). 13C NMR (125 MHz)
¼14.0 (q), 21.6 (t), 21.9
d
9 mg (87%). Yellow oil. IR (KBr): 3361 (NH), 2145 (C^C) cmꢂ1
.
1H
(q), 31.2 (t), 44.1 (t), 72.4 (d), 104.0 (s), 124.2 (d), 124.5 (s), 124.6 (s),
125.3 (d), 128.7 (d), 129.4 (d), 144.7 (s), 159.2 (s). MS m/z (relative in-
tensity, %): 401 (Mþ, 100), 359 (15), 316 (25), 232 (36), 190 (69), 156
(30), 130 (13). HRMS m/z calcd for C16H20NOIS: 401.0310; found:
401.0311.
NMR (500 MHz)
d
¼0.97, 1.47e1.57, 1.62e1.68, 2.51 (3H, t, J¼7.3 Hz,
2H, m, 2H, m, 2H, t, J¼7.1 Hz, n-Bu), 1.44, 5.63e5.73 (6H, d, J¼6.1 Hz,
1H, m, Oi-Pro), 7.03, 7.26, 7.37, 7.55e8.05 (1H, dd, J¼7.7, 7.6 Hz, 1H,
dd, J¼7.6, 6.1 Hz, 1H, dd, J¼7.7, 1.4 Hz, 1H, m, PheH), 8.55e9.05 (1H,
br, NH). 13C NMR (125 MHz)
d¼13.6 (q), 19.3 (t), 21.7 (q), 22.1 (t), 30.7
(t), 75.7 (s), 77.3 (d), 98.7 (s), 114.3 (s), 120.4 (d), 123.9 (d), 128.3 (d),
131.8 (d), 138.4 (s), 187.3 (s). MS m/z (relative intensity, %): 275 (Mþ,
8), 232 (58),172 (46), 130 (100),128 (36),102 (23), 77 (14). HRMS m/z
calcd for C16H21NOS: 275.1344; found: 275.1339.
4.8.5. 12,15-Bis(1-iodopentylidene)-12,15-dihydro-5H-dibenzo[d,i]
[1,2,6,8]dithiadiazacycloundecin-6(7H)-one 11. Pale yellow oil. IR
(KBr, neat): 3394 (NH), 1687 (C]O) cmꢂ1 1H NMR (500 MHz)
.
d
¼0.93, 1.23e1.41, 1.44e1.63, 2.55e2.73, 2.82e2.94 (6H, t, J¼7.3 Hz,
4H, m, 4H, m, 2H, m, 2H, m, n-Buꢁ2), 4.10e4.50 (2H, br, NHꢁ2),
6.93, 6.97, 7.08, 7.11, 7.18e7.25, 7.29e7.36 (1.2H, dd, J¼7.7, 1.5 Hz,
0.8H, dd, J¼7.7, 1.5 Hz, 0.8H, dd, J¼7.9, 1.2 Hz, 1.2H, dd, J¼7.9, 1.2 Hz,
4.8. Typical procedure for iodocyclization of 2-(hex-1-ynyl)
phenylcarbamothioate: formation of 2-alkoxy-4H-benzo[d]
[1,3]thiazine
2H, m, 2H, m, PheH). 13C NMR (125 MHz)
d¼13.86 and 13.88 (each
q), 21.9 (t), 31.53 and 31.55 (each t), 42.3 and 42.4 (each t), 112.9 (s),
124.8 and 125.1 (each d), 125.3 and 125.6 (each d), 129.6 (d), 131.36
(s), 131.43 (d), 131.5 (s), 134.7 and 134.9 (each s), 138.2 and 138.3
(each s). MS m/z (relative intensity, %): 690 (Mþ, 60), 563 (45), 499
(49), 204 (78), 191 (60), 173 (93), 161 (90), 130 (100). HRMS m/z
calcd for C25H28N2OI2S2: 689.9733; found: 689.9730.
To a solution of the thiourethane 9 (1 mmol) in dry CH2Cl2
(2 mL) were added I2 (330 mg, 1.3 mmol) and Cs2CO3 (489 mg,
1.5 mmol), and then the reaction mixture was stirred at room
temperature for 24 h. The mixture was diluted with CHCl3 (30 mL).
The organic layer was washed with 2% Na2S2O3 aq (15 mLꢁ3),
water (15 mLꢁ2), dried over anhydrous Na2SO4, and evaporated in
vacuo. The obtained residue was chromatographed on silica gel
using hexane/CHCl3 (1:5) as an eluent to give pure (4E)-4-(iodo-
methylidene)-3,1-benzothiazine 10 and 11.
4.9. (4Z)-2-(N,N-Diethylamino)-4-pentylidene-4H-benzo[d]
[1,3]thiazine 12
To
a solution of iodomethylidene-3,1-benzothiazine 3Aa
4.8.1. (4E)-4-(1-Iodopentylidene)-2-methoxy-4H-benzo[d][1,3]thia-
(50 mg, 0.12 mmol), formic acid (22 mg), and Et3N (34 mg) in dry
DMF (1 mL) was added PdCl2(PPh3)2 (5 mg). The mixture was
stirred at room temperature for 3days, and then diluted with
CHCl3 (30 mL). The organic layer was washed with satd NaHCO3
aq (15 mL), water (15 mLꢁ3), dried over anhydrous Na2SO4, and
evaporated in vacuo. The obtained residue was chromatographed
on silica gel using hexane/Et2O (1:10) as an eluent to give pure
dehalogenated compound. This compound was identical with the
authentic sample prepared in the previous paper.20 Yield: 15 mg
(43%). Yellow oil.
zine 10a. Yield: 172 mg (46%). Yellow oil. IR (KBr, neat): 1618
(C]N) cmꢂ1
.
1H NMR (500 MHz)
d
¼0.97, 1.35e1.44, 1.56e1.63,
3.00 (3H, t, J¼7.3 Hz, 2H, m, 2H, m, 2H, t, J¼7.6 Hz, n-Bu), 4.02
(3H, s, OMe), 7.19, 7.21, 7.34, 7.87 (1H, ddd, J¼7.7, 7.5, 1.2 Hz, 1H,
dd, J¼8.0, 1.2 Hz, 1H, ddd, J¼8.0, 7.5, 1.5 Hz, 1H, dd, J¼7.7, 1.5 Hz,
PheH). 13C NMR (125 MHz)
d
¼14.0 (q), 21.6 (t), 31.2 (t), 44.1 (t),
55.7 (q), 104.4 (s), 124.0 (s), 124.5 (d), 124.6 (s), 125.4 (d), 128.8
(d), 129.5 (d), 144.4 (s), 160.3 (s). MS m/z (relative intensity, %):
373 (Mþ, 100), 330 (35), 246 (20), 203 (75). HRMS m/z calcd for
C14H16NOIS: 372.9997; found: 372.9997.
4.8.2. (4E)-2-Ethoxy-4-(1-iodopentylidene)-4H-benzo[d][1,3]thiazine
4.10. (4E)-4-(1-Butylbenzylidene)-2(N,N-diethylamino)-4H-
benzo[d][1,3]thiazine 13
10b. Yield: 186 mg (48%). Yellow oil. IR (KBr, neat): 1618 (C]N) cmꢂ1
.
1H NMR (500 MHz)
d
¼0.97, 1.34e1.46, 1.56e1.64, 3.01 (3H, t, J¼7.3 Hz,
2H, m, 2H, m, 2H, t, J¼7.4 Hz, n-Bu), 1.38, 4.50 (3H, t, J¼7.1 Hz, 2H, q,
J¼7.1 Hz, OEt), 7.16e7.22, 7.33, 7.87 (2H, m, 1H, ddd, J¼7.6, 7.2, 1.4 Hz,
To a solution of iodomethylidene-3,1-benzothiazine 3Aa
(443 mg, 1.07 mmol), phenylboronic acid (261 mg, 2.14 mmol), and
Cs2CO3 (697 mg) in toluene (6 mL) was added Pd(OAc)2 (150 mg),
and then the reaction mixture was stirred at 100 ꢀC under argon
atmosphere for 2 days. After the reaction was over, the resulting
solution was diluted with benzene (30 mL). The organic layer was
washed with water (10 mLꢁ3), dried over anhydrous Na2SO4, and
evaporated in vacuo. The obtained residue was chromatographed
on silica gel using hexane/CHCl3 (1:2) as an eluent to give 13. Yield:
284 mg (73%). Orange oil. IR (KBr, neat): 1601 (C]N) cmꢂ1. 1H NMR
1H, dd, J¼8.3, 1.6 Hz, PheH). 13C NMR (125 MHz)
¼14.0 (q), 14.4 (q),
d
21.6 (t), 31.2 (t), 44.1 (t), 64.9 (t), 104.2 (s), 124.2 (s), 124.4 (d), 124.6 (s),
125.4 (d), 128.7 (d), 129.4 (d), 144.5 (s), 159.7 (s). MS m/z (relative in-
tensity, %): 387 (Mþ, 100), 344 (32), 260 (16), 217 (43), 189 (22), 156
(16). HRMS m/z calcd for C15H18NOIS: 387.0154; found: 387.0152.
4.8.3. (4E)-2-Benzyloxy-4-(1-iodopentylidene)-4H-benzo[d][1,3]
thiazine 10c. Yield: 189 mg (42%). Yellow oil. IR (KBr, neat): 1618
(C]N) cmꢂ1
.
1H NMR (500 MHz)
d
¼0.96, 1.34e1.44, 1.56e1.63,
(500 MHz, CDCl3)
d
¼0.89, 1.32e1.42, 2.74e2.81 (3H, t, J¼7.0 Hz, 4H,
3.01 (3H, t, J¼7.3 Hz, 2H, m, 2H, m, 2H, t, J¼7.4 Hz, n-Bu), 5.47 (2H,
m, 2H, n-Bu), 1.26, 3.66 (6H, t, J¼7.1 Hz, 4H, q, J¼7.1 Hz, NEt2), 6.48,
6.53, 7.02e7.10, 7.17e7.22 (1H, d, J¼7.6 Hz, 1H, ddd, J¼8.1, 5.9,
s, OCH2), 7.18e7.25, 7.32e7.41, 7.42e7.47, 7.88 (2H, m, 4H, m, 2H,
m, 1H, dd, J¼7.7, 1.2 Hz, PheH). 13C NMR (125 MHz)
d
¼14.0 (q), 21.6
2.5 Hz, 4H, m, 3H, m, PheH). 13C NMR (125 MHz, CDCl3)
d¼13.95
(t), 31.2 (t), 44.1 (t), 70.4 (t), 104.5 (s), 124.0 (s), 124.6 (d), 124.7 (s),
125.4 (d), 128.4 (d), 128.55 (d), 128.63 (d), 128.8 (d), 129.5 (d),
135.7 (s), 144.3 (s), 159.7 (s). MS m/z (relative intensity, %): 449
(q), 14.01 (q), 22.5 (t), 29.8 (t), 35.9 (t), 43.5 (t), 121.45 (s), 121.50 (d),
122.3 (s), 124.7 (d), 126.9 (d), 127.9 (d), 128.1 (d), 128.5 (d), 129.4 (d),
141.4 (s), 142.5 (s), 147.7 (s), 154.5 (s). MS (EI): m/z (relative

H. Sashida et al. / Tetrahedron 69 (2013) 6478e6487
6487
intensity, %) 364 (Mþ, 100), 335 (29), 321 (93), 307 (12), 250 (11).
Schmidt, R. R. J. Heterocycl. Chem. 1999, 36, 153e160; (h) Hari, A.; Miller, B. L. Org.
ꢁ
ꢁ
Lett. 2000, 2, 3667e3670; (i) Tarraga, A.; Molina, P.; Lopez, J. L. Tetrahedron Lett.
2000, 41, 4895e4899; (j) Deck, L. M.; Turner, S. D.; Deck, J. A.; Papadopoulos, E. P. J.
Heterocycl. Chem. 2001, 38, 343e347; (k) Abaev, V. T.; Tsiunchik, F. A.; Gutnov, A.
HRMS (EI) m/z Mþ calcd for C23H28N2S: 364.1973; found: 364.1971.
ꢁ
V.; Butin, A. V. Tetrahedron Lett. 2006, 47, 4029e4032; (l) Csomos, P.; Fodor, L.;
4.11. (4E)-2(N,N-Diethylamino)-4-[(1-phenylethynyl)pentyli-
dene]-4H-benzo[d][1,3]thiazine 14
ꢁ
€
Bernath, G.; Sinkkonen, J.; Salminen, J.; Wiinamaki, K.; Pihlaja, K. Tetrahedron
2008, 64,1002e1011; (m) Abaev, V. T.; Tsiunchik, F. A.; Gutnov, A. V.; Butin, A. V. J.
Heterocycl. Chem. 2008, 45, 475e481; (n) Butin, A. V.; Tsiunchik, F. A.; Avaev, V. T.;
Gutnov, A. V.; Cheshkov, D. A. Synthesis 2009, 2616e2626; (o) Gimbert, C.;
Vallribera, A. Org. Lett. 2009, 11, 269e271; (p) Fukamachi, S.; Konishi, H.;
Kobayashi, K. Synthesis 2010, 1593e1598; (q) Okuma, K.; Ozaki, S.; Nagahora, N.;
Shioji, K. Heterocycles 2011, 83, 1303e1313; (r) Qiu, G.; Hu, Y.; Ding, Q.; Peng, Y.;
Hu, X.; Wu, J. Chem. Commun. 2011, 9708e9710; (s) Ding, Q.; Liu, X.; Yu, J.;
Zhang, Q.; Wang, D.; Cao, B.; Peng, Y. Tetrahedron 2012, 68, 3937e3941.
4. (a) Ding, Q.; Wu, J. J. Comb. Chem. 2008, 10, 541e545; (b) Tang, R.-Y.; Luo, P.-S.;
Zhang, X.-G.; Zhong, P.; Li, J.-H. Synlett 2010, 1345e1350.
To a solution of iodomethylidene-3,1-benzothiazine 3Aa (550 mg,
1.33 mmol), phenylacetylene (163 mg, 1.6 mmol), and Et3N (1 mL) in
benzene (3 mL) were added PdCl2(PPh3)2 (20 mg) and CuI (15 mg).
The reaction mixture was stirred at room temperature for 2 days, and
diluted with benzene (50 mL). The organic layer was washed with
water (10 mLꢁ2), dried over anhydrous Na2SO4, and evaporated in
vacuo. The obtained residue was chromatographed on silica gel using
hexane/AcOEt (5:1) as an eluent to give 14. Yield: 464 mg (90%). Or-
5. (a) Schmittel, M.; Mahajan, A.; Steffen, J.-P. Synthesis 2004, 415e418; (b) Ding, Q.;
Cao, B.; Zong, Z.; Peng, Y. J. Comb. Chem. 2010, 12, 370e373.
6. Fernandes, M. A.; Reid, D. H. Synlett 2003, 2231e2233.
ange oil. IR (KBr, neat): 2185 (C^C), 1601 (C]N) cmꢂ1
.
1H NMR
7. Iodocyclization: (a) Vaino, A. R.; Szarek, W. A. Adv. Carbohydr. Chem. Biochem.
2001, 56, 9e63; (b) Togo, H.; Iida, S. Synlett 2006, 2159e2175; (c) Mphahlele, M. J.
Molecules 2009,14, 4814e4837; (d) Banerjee, A. K.; Laya, M. S.; Cabrera, E. V. Curr.
Org. Chem. 2011, 15, 1058e1080; (e) Godoi, B.; Schumacher, R. F.; Zeni, G. Chem.
Rev. 2011, 111, 2937e2980.
8. Furans: (a) Arcadi, A.; Cacchi, S.; Fabrizi, G.; Marinelli, F.; Moro, L. Synlett 1999,
1432e1434; (b) Arcadi, A.; Cacchi, S.; Giuseppe, S.; Fabrizi, G.; Marinelli, F. Org.
Lett. 2002, 4, 2409e2412; (c) Yue, D.; Yao, T.; Larock, R. C. J. Org. Chem. 2006, 71,
62e69; (d) Chen, Z.; Huang, G.; Jiang, H.; Huang, H.; Pan, X. J. Org. Chem. 2011,
76, 1134e1139; (e) Xu, M.; Zhang, X.-H.; Zhong, P. Tetrahedron Lett. 2011, 52,
6800e6804.
(500 MHz, CDCl3)
d
¼0.99, 1.42e1.51, 1.66e1.73, 2.63 (3H, t, J¼7.3 Hz,
2H, m, 2H, m, 2H, t, J¼7.6 Hz, n-Bu), 1.22, 3.59 (6H, t, J¼7.4 Hz, 4H, q,
J¼7.4 Hz, NEt2), 7.05, 7.14, 7.24e7.31, 7.38, 8.28 (1H, ddd, J¼8.0, 7.8,
1.4 Hz, 1H, dd, J¼8.0,1.1 Hz, 4H, m, 2H, dd, J¼8.0,1.7 Hz,1H, dd, J¼7.9,
1.4 Hz, PheH).13C NMR (125 MHz, CDCl3)
d¼13.9 (q),14.0 (q), 22.3 (t),
30.6 (t), 34.5 (t), 43.5 (t), 90.7 (s), 93.7 (s),104.2 (s),120.9 (s),121.2 (s),
121.7 (d), 123.7 (s), 125.2 (d), 127.0 (d), 128.0 (d), 128.3 (d), 129.4 (d),
131.2 (d), 146.6 (s), 152.6 (s). MS (EI): m/z (relative intensity, %) 388
(Mþ, 100), 359 (12), 345 (25), 317 (14), 287 (42), 275 (25). HRMS (EI)
m/z Mþ calcd for C25H28N2S: 388.1973; found: 388.1975.
9. Indoles: (a) Barluenga, J.; Trincado, M.; Rubio, E.; Gonzalez, J. M. Angew. Chem.,
Int. Ed. 2003, 42, 2406e2409; (b) Yue, D.; Yao, T.; Larock, R. C. J. Org. Chem. 2005,
70, 10292e10296.
10. Thiophenes: (a) Flynn, B. L.; Verdier-Pinard, P.; Hamel, E. Org. Lett. 2001, 3,
651e654; (b) Larock, R. C.; Yue, D. Tetrahedron Lett. 2001, 42, 6011e6013; Yue, D.;
Larock, R. C. J. Org. Chem. 2002, 67, 1905e1909; (d) Hessian, K. O.; Flynn, B. L. Org.
Lett. 2003, 5, 4377e4380; (e) Cho, C.-H.; Jung, D.-I.; Larock, R. C. Tetrahedron Lett.
2010, 51, 6485e6488.
11. Six-membered heterocycles: (a) Barange, D. K.; Batchu, V. R.; Gorja, D.;
Pattabiraman, V. R.; Tatini, L. K.; Babu, J. M.; Pal, M. Tetrahedron 2007, 63,
1775e1789; (b) Likhar, P. R.; Subhas, M. S.; Roy, M.; Roy, S.; Kantam, M. L. Helv.
Chim. Acta 2008, 91, 259e264; (c) Schneider, C. C.; Bortolatto, C.; Back, D. F.;
Menezes, P. H.; Zeni, G. Synthesis 2011, 413e418.
12. o-(Ethynyl)benzoic acid derivatives: (a) Yao, T.; Larock, R. C. Tetrahedron Lett.
2002, 43, 7401e7404; (b) Rossi, R.; Carpita, A.; Bellina, F.; Stabile, P.; Mannina, L.
Tetrahedron 2003, 59, 2067e2081; (c) Yao, T.; Larock, R. C. J. Org. Chem. 2003,
68, 5936e5942.
13. Seven-membered heterocycles Jiang, T.-S.; Zhang, X.-G.; Li, J.-H. Synthesis 2009,
3029e3038.
4.12. X-ray structure determination
Single crystals of 7Ae were obtained from solutions of CH2Cl2/
hexane after slow evaporation of the solvents at room temperature.
The structure analysis is based on 2511 observed reflections with
I>2.00s(I) and 139 variable parameters; red prisms, C19H19N2SI,
ꢀ
FW¼432.4, 233 K, triclinic, space group Pꢂ1, a¼9.3417(6) A,
b¼10.9081(7ꢀ) A, c¼10.9435(7) A,
a
¼69.699(1)ꢀ,
b
¼69.552(1)ꢀ,
ꢀ
ꢀ
3
ꢀ
g
¼64.961(1) , V¼917.6(1) A , Z¼2, R¼0.0272, Rw¼0.0709, GO
F¼1.077.
Single crystals of 3Da-Z were obtained from solutions of CHCl3/
14. Selenophenes: (a) Alves, D.; Luchese, C.; Nogueira, C. W.; Zeni, G. J. Org. Chem.
2007, 72, 6726e6734; (b) Speranca, A.; Godoi, B.; Costa, M. D.; Menezes, P. H.;
Zeni, G. Tetrahedron Lett. 2011, 52, 388e391.
hexane after slow evaporation of the solvents at room temperature.
The structure analysis is based on 3950 observed reflections with
I>2.00s(I) and 210 variable parameters; yellow prisms, C19H19N2SI,
15. 3-Iodobenzoselenophenes: Kesharwani, T.; Worlikar, S. A.; Larock, R. C. J. Org.
ꢀ
FW¼432.4, 230 K, monoclinic, space groupꢀP21/n, a¼13.079(3) A,
Chem. 2006, 71, 2307e2312.
3
ꢀ
ꢀ
ꢀ
16. Kaname, M.; Sashida, H. Tetrahedron Lett. 2011, 52, 3279e3282.
17. (a) Creeke, P. I.; Mellor, J. M. Tetrahedron Lett. 1989, 30, 4435e4438; (b) Murai, T.;
Niwa, H.; Kimura, T.; Shibahara, F. Chem. Lett. 2004, 33, 508e509.
18. Reviews: (a) Sashida, H. Rev. Heteroat. Chem. 2000, 22, 59e78; (b) Sashida, H. J.
Synth. Org. Chem., Jpn. 2001, 59, 355e362; (c) Sashida, H. Mini-Rev. Org. Chem.
2007, 4, 105e114; (d) Sashida, H.; Minoura, M. J. Synth. Org. Chem., Jpn. 2009, 67,
714e723; (e) Sashida, H. Heterocycles 2011, 83, 2223e2254.
b¼10.595(3) A, c¼14.231(4) A, ¼116.121(3) , V¼1770.6(8) A , Z¼4,
b
R¼0.0445, Rw¼0.1029, GOF¼1.038.
Acknowledgements
This work was supported in part by a Grant-in Aid for Scientific
Research from the Ministry of Education, Science and Culture, Japan
(23590023). Thanks are due to Mrs. Akinori Shimokado, Satoshi
Maruhashi, and Ms. Nobue Toyoda (Hokuriku University) for their
technical assistances.
19. Recent works: (a) Sashida, H.; Nakayama, A.; Kaname, M. Synthesis 2008,
3229e3236; (b) Sashida, H.; Nakabayashi, S.; Kaname, M.; Minoura, M.
Heterocycles 2010, 80, 1339e1352; (c) Sashida, H.; Satoh, H.; Ohyanagi, K.;
Kaname, M. Molecules 2010, 15, 1466e1472; (d) Sashida, H.; Kaname, M.; Ohya-
nagi, K. Heterocycles 2010, 82, 441e447; (e) Sashida, H.; Kaname, M.; Nakayama,
A.; Suzuki, H.; Minoura, M. Tetrahedron 2010, 66, 5149e5157; (f) Sashida, H.;
Nakabayashi, S.; Suzuki, H.; Kaname, M.; Minoura, M. Tetrahedron Lett. 2010, 51,
5395e5398; (g) Sashida, H.; Pan, C.; Kaname, M.; Minoura, M. Synthesis 2010,
3091e3096; (h) Kaname, M.; Minoura, M.; Sashida, H. Tetrahedron Lett. 2011, 52,
505e508; (i) Sashida, H.; Kaname, M. Heterocycles 2012, 84, 669e682.
20. Kaname, M.; Sashida, H. Tetrahedron Lett. 2012, 53, 748e751.
References and notes
1. This paper constitutes Part 38 in the series ‘Studies on Chalcogen-containing
Heterocycles’, For Part 37: mCPBA oxidation of isotellurochromenes and iso-
selenochromenes Sashida, H.; Kaname, M.; Ohyanagi, K.; Minoura, M. Tetrahe-
dron 2012, 68, 10502e10509 Special Issue of Progress in Organoselenium and
Organotellurium Chemistry.
21. Diffraction data were collected on a Bruker Apex-II CCD diffractometer equipped
ꢀ
with a graphite monochromated Mo K
a
radiation source (
l¼0.71073 A). The
structures were solved by direct methods (SHELXS-97), and refined by full-matrix
least-square methods on F2 for all reflections (SHELXL-97) with all non-hydrogen
atoms anisotropic and all hydrogen atoms isotropic. CCDC-907305 (for 3Da-Z)
and 885264 (for 7Ae) contain the supplementary crystallographic data for this
paper. The data can be obtained freeofcharge fromthe Cambridge Crystallographic
Data Centre via http://www.ccdc.cam.ac.uk/products/csd/request/.
2. (a) Morgenstern, O.; Schuster, R.; Finke, M.; Richter, P. H. Pharmazie 1996, 51,
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Lindamood, B. S.; Papadopoulos, E. P. Synthesis 1984, 68e71; (d) Nishio, T.
Tetrahedron Lett. 1995, 36, 6113e6116; (e) Nishio, T. J. Org. Chem. 1997, 62,
1106e1111; (f) Butin, A. V.; Abaev, V. T.; Stroganova, T. A.; Gutnov, A. V. Mole-
cules 1997, 2, 62e68; (g) El-Desoky, S. I.; Kandeel, E. M.; Abd-el-Raman, A. H.;
22. (a) Benati, L.; Calestani, G.; Leadini, R.; Minozzi, M.; Nanni, D.; Spagnolo, P.;
Strazzari, S.; Zanardi, G. J. Org. Chem. 2003, 68, 3454e3464; (b) Saito, T.;
Nihei, H.; Otani, T.; Suyama, T.; Furukawa, N.; Saito, M. Chem. Commun. 2008,
172e174.