Synthesis of 2-(arylthio)benzoates by [3+3] cyclocondensations of 3-arylthio-1-silyloxy-1,3-butadienes with 3-oxo-orthoesters, 1,1,3,3-tetramethoxypropane and 1,1-bis(methylthio)-1-en-3-ones

Article abstract of DOI:10.1016/j.tet.2009.08.078

A variety of 2-arylthio-4-methoxybenzoates are regioselectively prepared by TiCl₄-mediated [3+3] cyclocondensations of 3-arylthio-1-trimethylsilyloxy-1,3-butadienes with 3-oxo-orthoesters. Unsubstituted 2-(arylthio)benzoates were prepared by Me

Full text of DOI:10.1016/j.tet.2009.08.078

Tetrahedron 65 (2009) 8794–8801
Contents lists available at ScienceDirect
Tetrahedron
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Synthesis of 2-(arylthio)benzoates by [3þ3] cyclocondensations of 3-arylthio-
1-silyloxy-1,3-butadienes with 3-oxo-orthoesters, 1,1,3,3-tetramethoxypropane
and 1,1-bis(methylthio)-1-en-3-ones
,
,b,
Muhammad Imran a, Inam Iqbal a, Nasir Rasool a c, Christine Fischer b, Peter Langer a
*
a Institut fu¨r Chemie, Universita¨t Rostock, Albert-Einstein-Str. 3a, 18059 Rostock, Germany
b Leibniz-Institut fu¨r Katalyse e. V. an der Universita¨t Rostock, Albert-Einstein-Str. 29a, 18059 Rostock, Germany
c G.C. University Faisalabad, Department of Chemistry, Faisalabad, Pakistan
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 27 June 2009
Received in revised form 25 August 2009
Accepted 29 August 2009
Available online 3 September 2009
A variety of 2-arylthio-4-methoxybenzoates are regioselectively prepared by TiCl4-mediated [3þ3] cy-
clocondensations of 3-arylthio-1-trimethylsilyloxy-1,3-butadienes with 3-oxo-orthoesters. Unsubstituted
2-(arylthio)benzoates were prepared by Me3SiOTf-catalyzed cyclization of 3-arylthio-1-trimethylsilyloxy-
1,3-butadienes with 1,1,3,3-tetramethoxypropane. The TiCl4-mediated cyclization of 3-arylthio-1-trime-
thylsilyloxy-1,3-butadienes with 1,1-bis(methylthio)-1-en-3-ones results in regioselective formation of
2-arylthio-6-(methylthio)benzoates.
Keywords:
Arenes
Ó 2009 Elsevier Ltd. All rights reserved.
Cyclizations
Diaryl sulfides
Regioselectivity
Silyl enol ethers
1. Introduction
butadiene with 3-silyloxy-2-en-1-ones and with enones.10 We
have reported the cyclization of 3-arylthio-1-trimethylsilyloxy-
Diaryl sulfides occur in several pharmacologically relevant
natural products (e.g., the lissoclibadins, dibenzothiophenes, cyclic
sulfides, varacins).1 Diaryl sulfides have been prepared by reaction
of sulfur2 or sulfur dichloride3 with arenes, by reaction of organo-
metallic reagents with chlorophenyl-sulfides4 or by base-mediated
reactions of thiophenols with chloroarenes.5 The scope of these
methods is limited by polysulfide formation and low regiose-
lectivities. These problems can be successfully addressed by the
application of novel transition metal-catalyzed6 and metal-free7
C–S coupling reactions. However, the synthesis of the starting
materials, substituted aryl halides or triflates, can be a difficult and
tedious task.
1,3-butadienes with 1,1-diacylcyclopropanes,11 3-alkoxy-2-en-1-
ones,12 1,1,3,3-tetramethoxypropane13 and dimethyl acetylene-
dicarboxylate.14 Recently, we have reported preliminary results
related to the synthesis of 2-arylthio-4-methoxybenzoates by
cyclocondensation of 3-arylthio-1-trimethylsilyloxy-1,3-butadi-
enes with 3-oxo-orthoesters.15 Herein, we report full details of
these studies. In addition, a full account of the cyclization of 3-
arylthio-1-trimethylsilyloxy-1,3-butadienes with 1,1,3,3,-tetra-
methoxypropane is included. We also report, for the first time,
the synthesis of 2-arylthio-6-(methylthio)benzoates by cycliza-
tion of 3-arylthio-1-trimethylsilyloxy-1,3-butadienes with 1,1-
bis(methylthio)-1-en-3-ones.
An alternative strategy relies on a building block approach.
For example, diaryl sulfides have been prepared by cobalt(I)-
catalyzed [4þ2] cycloaddition of alkynyl sulfides with 1,3-buta-
dienes.8 3- and 5-(Arylthio)salicylates have been prepared by
TiCl4-mediated formal [3þ3] cyclizations of 1,3-bis(silyloxy)-1,3-
butadienes with 3-silyloxy-2-en-1-ones.9 Chan et al. reported
the reaction of 1-methoxy-3-phenylthio-1-trimethylsilyloxy-1,3-
The chemistry reported herein provides a regioselective ap-
proach to a wide range of novel diaryl sulfides, which are not
readily available by other methods. In contrast to the C–S coupling
reactions outlined above, our method relies on the assembly of one
of the two arene moieties.
2. Results and discussion
The known 3-oxo-orthoesters 1a,b were prepared, according to
* Corresponding author. Fax: þ49 381 4986412.
E-mail address: peter.langer@uni-rostock.de (P. Langer).
literature procedures,16 by condensation of 1,1-dichloroethene with
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.08.078

M. Imran et al. / Tetrahedron 65 (2009) 8794–8801
8795
acetyl and propionyl chloride, respectively, to give 3,3,3-tri-
chloroketones, which were subsequently transformed into the
products by reaction with methanol. The known 3-arylthio-1-tri-
methylsilyloxy-1,3-butadienes 2a–m were prepared from methyl
acetoacetate, methyl 3-oxopentanoate and various thiophenols in
two steps.12
The TiCl4-mediated cyclization of 1a with 3-phenylthio-1-tri-
methylsilyloxy-1,3-butadiene 2a afforded 2-phenylthio-4-methoxy-
benzoate 3a (Scheme 1). The cyclization proceeded with very good
regioselectivity. The formation of 2-phenylthio-6-methoxybenzoate,
a regioisomer of 3a, was not observed. The best yields were obtained
when a stoichiometric ratio of 2a/1a/TiCl4¼1.0:1.5:1.5 was used and
when the reaction was carried out in a fairly concentrated solution
(c(1a)¼0.33 M). The relatively low yield (55%) can be explained by
practical problems during the chromatographic purification and by
partial hydrolysis of the starting materials.
benzoate moiety (substituents R1 and R2) and at the arylthio group.
The yields of the products 3h,i, derived from dienes 2h,i, containing
a substituent located at the terminal carbon atom, are lower than the
yields of the other products. The yields of the products derived from
1a are slightly higher than the yields of the products derived from
1b. The substituents located at the aryl group of the diene seem to
have no major influence on the yield. The moderate yields can be
explained by problems during the chromatographic purification and
by partial hydrolysis of the starting materials. In some reactions
a small amount of hydrolyzed starting material was recovered.
ArS
OSiMe3
OMe
SAr
O
R2
R2
OMe
2a-i
i
+
R1
O
OMe
MeO
R1
PhS
OSiMe3
OMe
MeO
3a-l
MeO
SPh O
1a,b
2a
Scheme 2. Synthesis of arenes 3a–l; conditions: i: (1) TiCl4 (1.0 equiv), CH2Cl2, ꢀ78/
TiCl4
OMe
20 ꢁC, 20 h; (2) HCl (10%).
+
i
OMe O
MeO
Me
Table 1
Synthesis of 3a–l
MeO
MeO
3a (55%)
Me
1a
1
2
3
R1
R2
Ar
Yielda % (3)
_
a
a
a
a
a
a
a
a
a
b
b
b
a
b
c
d
e
f
g
h
i
a
b
c
d
e
f
g
h
i
Me
Me
Me
Me
Me
Me
Me
Me
Me
Et
H
H
H
H
H
H
H
Me
Me
H
H
H
Ph
55
50
46
51
45
40
46
37
35
37
38
40
TiOCl2
TiCl ,
2a
_
3-MeC6H4
3-ClC6H4
4-MeC6H4
4-EtC6H4
4-FC6H4
4-ClC6H4
Ph
4-EtC6H4
3-ClC6H4
4-MeC6H4
4-ClC6H4
+ H2O
4
HCl
Me3SiOMe
(HO)Cl3Ti
SPh O
PhS
O
OMe
Me
OMe
Me
MeO
c
d
g
j
k
l
MeO
Et
Et
TiCl4
O
MeO
D
A
a
Isolated yields.
[HCl]
SPh O
HCl
The reaction of 3-phenylthio-1-silyloxy-1,3-butadiene 2a with
1,1,3,3-tetramethoxypropane (4), in the presence of catalytic
amounts of Me3SiOTf, afforded the 2-(phenylthio)benzoate 5a
(Scheme 3). The best yields were obtained when 0.1 equiv of Lewis
acid was used. The use of 0.2 or 1.0 equiv of Me3SiOTf did not result
in an increase of the yield. The yields decreased when less than
0.1 equiv of Lewis acid was employed. The use of 1.0 equiv of TiCl4
proved to be possible, but again did not increase the yield. The work-
up procedure (diluted hydrochloric acid), the temperature (ꢀ78/
20 ꢁC, 20 h), and the concentration (ca. 2 mL of CH2Cl2 per 1 mmol of
4) proved to be important parameters during the optimization. The
high concentration is a significant difference to the procedure
reported17 for the Me3SiOTf-catalyzed cyclization of 1,3-bis(silyl-
oxy)-1,3-butadienes with 4. The use of tetraethoxypropane rather
than 4 proved to be unsuccessful. The use of trifluoroacetic acid or
triflic acid (rather than Me3SiOTf) failed to give the desired product.
The formation of 5a can be explained by Me3SiOTf-catalyzed
formation of oxonium cation E, attack of the terminal carbon atom
of 2a onto E to give intermediate F, Me3SiOTf-catalyzed formation
of oxonium cation G, cyclization to give intermediate H and sub-
sequent aromatization by extrusion of methanol. The suggested
mechanism has not been experimentally proved.
SPh O
[HCl]
OMe
Me
OTiCl3
OMe
Me
OTiCl3
MeO
MeO
MeO
MeOH
B
C
Scheme 1. Possible mechanism of the formation of arene 3a; i: (1) TiCl4 (1.0 equiv),
CH2Cl2, ꢀ78/20 ꢁC, 20 h; (2) HCl (10%).
The formation of 3a can be explained by the mechanism depicted
in Scheme 1. The TiCl4-mediated attack of diene 2a to the orthoester
gives intermediate A. The attack of carbon atom C-2 of A onto the
carbonyl group results in cyclization (intermediate B). Aromatization
(intermediates C and D) and hydrolysis (during the aqueous work-up)
provide the final product. The cyclization might proceed also by TiCl4-
mediated extrusion of methanol from 1a to give 4,4-dimethoxy-3-
buten-2-one, conjugate addition of the terminal carbon atom of 2a
onto the latter and subsequent cyclization. This process would follow
a mechanism earlier suggested for the cyclization of 3-arylthio-1-
trimethylsilyloxy-1,3-butadienes with 3-alkoxy-2-en-1-ones.12
The TiCl4-mediated cyclization of 3-oxo-orthoesters 1a,b with 3-
arylthio-1-trimethylsilyloxy-1,3-butadienes 2a–i gave the novel 2-
arylthio-4-methoxybenzoates 3a–l (Scheme 2, Table 1). Various
substituents can be introduced at carbon atoms C3 and C6 of the
The cyclization of dienes 2a–j,n–p with 4 afforded the 2-
(arylthio)benzoates 5a–m in moderate yields (Scheme 4, Table 2).
Comparable yields were obtained for products 5b,d, which are
derived from dienes containing an electron-withdrawing halogen
atom located at the arylthio group, and for products 5a,c,e.

8796
M. Imran et al. / Tetrahedron 65 (2009) 8794–8801
trimethylsilyloxy-1,3-butadienes 2b,d,g,h,k with 1,1-bis(methyl-
PhS
OSiMe3
thio)-1-en-3-one 619 afforded the novel 2-arylthio-6-(methyl-
thio)benzoates 7a–e in 37–55% yield (Scheme 5, Table 3). The
formation of products 7 might be explained by TiCl4-mediated attack
of the diene onto the carbonyl group of 4 to give intermediate E,
formation of an allylic cation and cyclization (intermediate F). The
extrusion of MeSH leads to the final product.
O
SPh
OMe
OMe
OMe
OMe
OMe
2a
MeO
i
4
5a (53%)
MeOH
Me3SiOTf
Me3SiOMe
ArS
OSiMe3
OMe
R
SAr
O
SPh O
_
R
2b,d,g,h,k
i
OMe
SMe
OMe
OMe
OTf
+
+
OMe
OMe
O
SMe
SMe
MeO
Me
MeO
Me
E
H
7a-e
6
2a
TfOH
Me3SiOTf
MeSH
TiCl4
Me3SiCl
O
O
O
PhS
OMe
_
PhS
OMe
OMe
OMe
SAr
O
Me3SiOTf
ArS
OMe
R
OTf
R
OMe
SMe
SMe
SMe
SMe
OMe
+
MeO
MeO
Me3SiOMe
Cl3TiO
Me
Me
G
F
Scheme 3. Possible mechanism of the formation of 5a; conditions: i: (1) Me3SiOTf
(0.1 equiv), CH2Cl2, ꢀ78/20 ꢁC, 20 h; (2) HCl, H2O.
Me3SiOTiCl3
J
I
Scheme 5. Synthesis of arenes 7a–e; conditions: i: (1) TiCl4, ꢀ78/20 ꢁC, 20 h; (2) HCl
(10%).
SAr OSiMe3
SAr O
R
OMe
2a-j,n-p
R
Table 3
Synthesis of 7a–e
OMe
i
2
7
R
Ar
Yielda % (7)
OMe OMe
OMe
4
d
b
g
h
k
a
b
c
d
e
H
H
H
Me
Me
4-MeC6H4
3-MeC6H4
4-ClC6H4
Ph
55
37
49
48
51
+
MeO
5a-m
4-MeC6H4
Scheme 4. Synthesis of 5a–m; conditions: i: (1) Me3SiOTf (0.1 equiv), CH2Cl2, ꢀ78/
a
Yields of isolated products.
20 ꢁC, 20 h; (2) HCl, H2O.
The chromatographic purification of products 7a–e proved to be
Table 2
Synthesis of 5a–m
rather difficult. A further variation of the diene and a variation of
the 1,1-bis(methylthio)-1-en-3-one proved, in principle, to be
possible. Inspection of the NMR spectra of the crude products
showed that the expected products were formed. However, their
isolation in pure form was not possible in many cases. Therefore,
these experiments are not included herein.
In conclusion, we have reported the synthesis of 2-arylthio-4-
methoxybenzoates by cyclocondensation of 3-arylthio-1-trime-
thylsilyloxy-1,3-butadienes with 3-oxo-orthoesters. In addition, we
have reported the synthesis of 2-arylthio-6-(methylthio)benzoates
by cyclization of 3-arylthio-1-trimethylsilyloxy-1,3-butadienes
with 1,1-bis(methylthio)-1-en-3-ones. The chemistry reported
herein provides a regioselective approach to a wide range of novel
diaryl sulfides, which are not readily available by other methods.
2
5
R
Ar
Yielda % (5)
a
f
b
c
d
j
k
h
l
a
b
c
d
e
f
g
h
i
H
H
H
H
H
H
Me
Me
Me
Et
Ph
53
47
54
51
53
33
46
50
44
50
55
45
48
4-FC6H4
3-MeC6H4
3-ClC6H4
4-MeC6H4
2-Naph
4-MeC6H4
Ph
4-FC6H4
Ph
4-EtC6H4
4-EtC6H4
4-ClC6H4
m
e
i
j
k
l
H
Me
Me
n
m
a
Isolated yields.
3. Experimental section
3.1. General comments
Recently, we have reported the synthesis of 6-(methyl-
thio)salicylates by cyclization of 1,3-bis(trimethylsilyloxy)-1,3-buta-
dienes with 1,1-bis(methylthio)-1-en-3-ones.18 Based on these
results we studied related cyclization reactions of 3-arylthio-1-tri-
methylsilyloxy-1,3-butadienes. The cyclization of 3-arylthio-1-
All solvents were dried by standard methods and all reactions
were carried out under an inert atmosphere. For 1H and 13C NMR

M. Imran et al. / Tetrahedron 65 (2009) 8794–8801
8797
spectra the deuterated solvents indicated were used. Mass spec-
HRMS (EI): calcd for
322.04244.
C
16H15O3SCl (Mþ): 322.04249, found:
trometric data (MS) were obtained by electron ionization (EI,
70 eV), chemical ionization (CI, isobutane) or electrospray ioniza-
tion (ESI). For preparative scale chromatography silica gel 60
(0.063–0.200 mm, 70–230 mesh) was used.
3.2.4. Methyl 2-methoxy-4-methyl-6-(4-methylphenyl-sulfanyl)-ben-
zoate (3d). Starting with 2d (441 mg, 1.5 mmol) and 1a (364 mg,
2.25 mmol), 3d was isolated as a highly viscous colourless oil
(231 mg, 51%); 1H NMR (250 MHz, CDCl3):
d
¼2.24 (s, 3H, CH3), 2.27
(s, 3H, CH3), 3.59 (s, 3H, OCH3), 3.79 (s, 3H, OCH3), 6.49–7.18 (m, 6H,
ArH); 13C NMR (63 MHz, CDCl3):
¼20.4 (CH3), 21.1 (CH3), 51.9
3.2. General experimental procedure for the synthesis
of diaryl sulfides 3a–l
d
(OCH3), 52.2 (OCH3), 114.1, 114.5, 128.5, 129.0, 129.3 (CHAr), 132.2 (C),
132 (CHAr), 134.4, 136.8, 138.3, 139.0, 160.2, 168.8 (C); IR (KBr, cmꢀ1):
v¼3434 (w), 2998 (w), 2947 (w), 2834 (w), 2735 (w), 2664 (w), 1083
(m), 1738 (m), 1710 (s), 1650 (m), 1572 (m), 1473 (m), 1438 (s), 1303
(m), 1248 (m), 1195 (s), 1153 (s), 1099 (s), 1067 (m), 1022 (s), 1000
(m), 886 (m), 844 (m), 803 (m), 745 (s), 703 (s), 688 (s), 608 (m); MS
(EI, 70 eV): m/z (%)¼303 (19), 302 (Mþ, 100), 272 (11), 271 (61), 270
(21), 269 (86), 256 (18), 255 (49), 228 (17), 227 (13), 186 (11), 184
(15); HRMS (EI): calcd for C17H18O3S (Mþ): 302.09712, found:
302.09715.
To a dichloromethane solution (3 mL/mmol of 1) of 2 (1.5 mmol)
and of 1 (2.25 mmol) was added TiCl4 (2.25 mmol) at ꢀ78 ꢁC. The
solution was allowed to warm to 20 ꢁC within 20 h. To the solution
was added hydrochloric acid (10%, 25 mL). The organic and the
aqueous layers were separated and the latter was extracted with
dichloromethane (3ꢂ20 mL). The combined organic layers were
dried (Na2SO4), filtered, and the filtrate was concentrated in vacuo
and the residue was purified by chromatography (silica gel, EtOAc/
n-heptane¼1:9).
3.2.1. Methyl 2-methoxy-4-methyl-6-phenylsulfanyl-benzoate (3a).
Starting with 2a (420 mg, 1.5 mmol) and 1a (364 mg, 2.25 mmol),
3a was isolated as a highly viscous colourless oil (238 mg, 55%); 1H
3.2.5. Methyl 2-methoxy-4-methyl-6-(4-ethylphenyl-sulfanyl)-ben-
zoate (3e). Starting with 2e (462 mg, 1.5 mmol) and 1a (364 mg,
2.25 mmol), 3e was isolated as a highly viscous colourless oil
NMR (250 MHz, CDCl3):
3.75 (s, 3H, OCH3), 6.44–7.22 (m, 7H, ArH); 13C NMR (63 MHz,
CDCl3):
¼20.0 (CH3), 50.7 (OCH3), 51.0 (OCH3), 110.2 (2CHAr), 129.1
d
¼2.25 (s, 3H, CH3), 3.57 (s, 3H, OCH3),
(213 mg, 45%); 1H NMR (250 MHz, CDCl3):
d
¼1.14 (t, J¼7.6 Hz, 3H,
CH3), 2.25 (s, 3H, CH3), 2.54 (q, J¼7.6 Hz, 2H, CH2), 3.56 (s, 3H,
d
OCH3), 3.79 (s, 3H, OCH3), 6.39–7.26 (m, 6H, ArH); 13C NMR
(2C), 129.5, 130.7, 132.5 (CHAr), 135.9 (2CHAr), 139.6 (2C), 160.5,
165.8 (C); IR (KBr, cmꢀ1): v¼3400 (w), 3056 (w), 2992 (w), 2948
(w), 2922 (w), 2850 (w), 2664 (w), 1083 (m), 1738 (m), 1710 (s),
1650 (m), 1571 (m), 1473 (m), 1438 (s), 1303 (m), 1248 (m), 1195 (s),
1153 (s), 1099 (s), 1067 (m), 1022 (s), 1000 (m), 886 (m), 844 (m),
803 (m), 745 (s), 703 (s), 688 (s), 608 m; MS (EI, 70 eV): m/z
(%)¼289 (18), 288 (Mþ, 100), 272 (12), 271 (61), 270 (21), 269 (86),
256 (18), 255 (49), 228 (17), 227 (13), 185 (10), 184 (17); HRMS (EI):
calcd for C16H16O3S (Mþ): 288.09612, found: 288.09715.
(63 MHz, CDCl3):
d¼14.3 (CH3), 19.4 (CH3), 27.2 (CH2CH3), 50.9
(OCH3), 54.1 (OCH3), 112.6, 113.0 (CHAr), 125.9 (C), 127.8 (2CHAr),
129.9 (C), 131.9 (2CHAr), 136.8, 137.4, 143.3, 159.2, 167.7 (C); IR (KBr,
cmꢀ1): v¼3070 (w), 3023 (w), 2959 (w), 2930 (w), 2870 (w), 1911
(w), 1083 (m), 1738 (m), 1710 (s), 1650 (m), 1572 (m), 1473 (m), 1438
(s),1303 (m),1248 (m),1195 (s),1153 (s),1099 (s),1067 (m),1022 (s),
1000 (m), 886 (m), 844 (m), 803 (m), 745 (s), 703 (s), 688 (s), 608
(m); MS (EI, 70 eV): m/z (%)¼317 (20), 316 (Mþ, 100), 285 (45), 284
(17), 283 (51), 269 (13), 256 (10), 255 (40), 121 (26), 186 (11), 184
(15); HRMS (EI): calcd for C18H20O3S (Mþ): 316.11277, found:
316.11293.
3.2.2. Methyl 2-methoxy-4-methyl-6-(3-methylphenyl-sulfanyl)-ben-
zoate (3b). Starting with 2b (441 mg, 1.5 mmol) and 1a (364 mg,
2.25 mmol), 3b was isolated as a highly viscous colourless oil
3.2.6. Methyl 2-methoxy-4-methyl-6-(4-flourophenyl-sulfanyl)-ben-
zoate (3f). Starting with 2f (447 mg, 1.5 mmol) and 1a (364 mg,
2.25 mmol), 3f was isolated as a highly viscous colourless oil
(227 mg, 50%); 1H NMR (250 MHz, CDCl3):
d
¼2.23 (s, 3H, CH3),
2.27 (s, 3H, CH3), 3.59 (s, 3H, OCH3), 3.79 (s, 3H, OCH3), 6.49–7.18
(m, 6H, ArH); 13C NMR (63 MHz, CDCl3):
¼20.3 (CH3), 21.2 (CH3),
d
(183 mg, 40%); 1H NMR (250 MHz, CDCl3):
d
¼2.27 (s, 3H, CH3), 3.59
(s, 3H, OCH3), 3.81 (s, 3H, OCH3), 6.37–7.29 (m, 6H, ArH); 13C NMR
(63 MHz, CDCl3):
¼20.4 (CH3), 51.9 (OCH3), 55.2 (OCH3), 113.8,
51.9 (OCH3), 52.2 (OCH3), 114.1, 114.5, 128.5, 129.0, 129.3 (CHAr),
132.2 (C), 132 (CHAr), 134.4, 136.8, 138.3, 139.0, 160.2, 168.8 (C); IR
(KBr, cmꢀ1): v¼3435 (w), 2998 (w), 2947 (w), 2834 (w), 2735 (w),
2664 (w), 1083 (m), 1738 (m), 1710 (s), 1650 (m), 1571 (m), 1473
(m), 1438 (s), 1303 (m), 1248 (m), 1195 (s), 1153 (s), 1099 (s), 1067
(m), 1022 (s), 1000 (m), 886 (m), 844 (m), 803 (m), 745 (s), 703 (s),
688 (s), 608 (m); MS (EI, 70 eV): m/z (%)¼303 (19), 302 (Mþ, 100),
272 (11), 271 (61), 270 (21), 269 (86), 256 (18), 255 (49), 228 (17),
227 (13), 186 (11), 184 (15); HRMS (EI): calcd for C17H18O3S (Mþ):
302.09712, found: 302.09715.
d
114.4, 116.2, 116.6 (CHAr), 127.1, 129.7, 129.8 (C), 134.7, 134.9 (CHAr),
137.2, 138.6, 160.3, 168.6 (C); IR (KBr, cmꢀ1): v¼3055 (w), 2999 (w),
2947 (w), 2835 (w), 1725 (s), 1590 (s), 1562 (s), 1459 (s), 1427 (m),
1399 (m), 1304 (m), 1266 (s), 1218 (s), 1187 (m), 1137 (s), 1090 (m),
1071 (m), 1047 (s), 995 (m), 959 (m), 849 (m), 773 (s), 677 (s), 608
(m); MS (EI, 70 eV): m/z (%)¼307 (14), 306 (Mþ 79), 276 (10), 275
(57), 274 (30), 273 (100), 260 (12), 232 (14), 203 (10), 202 (10), 189
(10), 185 (10), 184 (18); HRMS (EI): calcd for C16H15O3SF (Mþ):
306.04622, found: 306.046232.
3.2.3. Methyl 2-methoxy-4-methyl-6-(3-chlorophenyl-sulfanyl)-ben-
zoate (3c). Starting with 2c (471 mg, 1.5 mmol) and 1a (364 mg,
2.25 mmol), 3c was isolated as a highly viscous colourless oil
3.2.7. Methyl 2-methoxy-4-methyl-6-(4-chlorophenyl-sulfanyl)-ben-
zoate (3g). Starting with 2g (471 mg, 1.5 mmol) and 1a (364 mg,
2.25 mmol), 3g was isolated as a highly viscous colourless oil
(222 mg, 46%); 1H NMR (250 MHz, CDCl3):
d
¼2.27 (s, 3H, CH3), 3.64
(s, 3H, OCH3), 3.77 (s, 3H, OCH3), 6.58–7.23 (m, 6H, ArH); 13C NMR
(63 MHz, CDCl3):
¼20.3 (CH3), 52.0 (OCH3), 55.3 (OCH3), 115.6
(222 mg, 46%); 1H NMR (250 MHz, CDCl3):
d
¼2.28 (s, 3H, CH3), 3.65
(s, 3H, OCH3), 3.77 (s, 3H, OCH3), 6.58–7.23 (m, 6H, ArH); 13C NMR
(63 MHz, CDCl3):
¼20.3 (CH3), 52.0 (OCH3), 55.3 (OCH3), 115.6
d
(2CHAr), 127.2, 128.9, 130.0, 130.4 (CHAr), 134.1, 134.5, 134.7, 137.9,
138.5, 160.3, 168.6 (C); IR (KBr, cmꢀ1): v¼3055 (w), 2999 (w), 2947
(w), 2835 (w), 1725 (s), 1590 (s), 1562 (s), 1459 (s), 1427 (m), 1399
(m), 1304 (m), 1266 (s), 1218 (s), 1187 (m), 1137 (s), 1090 (m), 1071
(m), 1047 (s), 995 (m), 959 (m), 849 (m), 773 (s), 677 (s), 608 (m);
MS (EI, 70 eV): m/z (%)¼324 (26), 323 (13), 322 (Mþ 70), 293 (29),
292 (17), 291 (83), 290 (27), 289 (100), 255 (17), 185 (10), 184 (18);
d
(2CHAr), 127.2, 128.9, 130.0, 130.4 (CHAr), 134.1, 134.5, 134.7, 137.9,
138.5, 160.3, 168.6 (C); IR (KBr, cmꢀ1): v¼3055 (w), 2999 (w), 2947
(w), 2835 (w), 1725 (s), 1590 (s), 1561 (s), 1459 (s), 1427 (m), 1399
(m), 1304 (m), 1266 (s), 1218 (s), 1187 (m), 1137 (s), 1090 (m), 1071
(m), 1047 (s), 995 (m), 959 (m), 849 (m), 773 (s), 677 (s), 608 (m);
MS (EI, 70 eV): m/z (%)¼324 (26), 323 (13), 322 (Mþ 70), 293 (29),

8798
M. Imran et al. / Tetrahedron 65 (2009) 8794–8801
292 (17), 291 (83), 290 (27), 289 (100), 255 (17), 185 (10), 184 (18);
HRMS (EI): calcd for C16H15O3SCl (Mþ): 322.04249, found:
322.04244.
677 (s), 608 (m); MS (EI, 70 eV): m/z (%)¼316 (Mþ, 45), 285 (23),
284 (20), 383 (100), 269 (31), 255 (17), 185 (10), 184 (18); HRMS
(EI): calcd for C18H20O3S (Mþ): 316.11277, found: 316.11268.
3.2.8. Methyl 6-methoxy-3,4-dimethyl-2-phenylsulfanyl-benzoate
(3h). Starting with 2h (441 mg, 1.5 mmol) and 1a (364 mg,
2.25 mmol), 3h was isolated as a highly viscous colourless oil
3.2.12. Methyl 2-(4-chlorophenylsulfanyl)-4-ethyl-6-methoxybenzoate
(3l). Starting with 2g (471 mg, 1.5 mmol) and 1b (396 mg,
2.25 mmol), 3l was isolated as a highly viscous colourless oil
(167 mg, 37%); 1H NMR (250 MHz, CDCl3):
d
¼2.11 (s, 3H, CH3),
2.25 (s, 3H, CH3), 3.72 (s, 3H, OCH3), 3.76 (s, 3H, OCH3), 6.66–7.18
(m, 6H, ArH); 13C NMR (63 MHz, CDCl3):
¼13.3 (CH3), 19.7 (CH3),
(201 mg, 40%); 1H NMR (250 MHz, CDCl3):
d
¼1.55 (t, J¼7.6 Hz, 3H,
CH3), 2.56 (q, J¼7.6 Hz, 2H, CH2), 3.65 (s, 3H, OCH3), 3.76 (s, 3H,
OCH3), 6.58–7.23 (m, 6H, ArH); 13C NMR (63 MHz, CDCl3):
¼15.3
d
d
52.0 (OCH3), 55.6 (OCH3), 112.9, 125.3 (CHAr), 127.2, 128.7 (2CHAr),
129.3, 129.5, 129.9, 133.5, 137.3, 158.4, 169.6 (C); IR (KBr, cmꢀ1):
v¼3434 (w), 2998 (w), 2947 (w), 2834 (w), 2735 (w), 2664 (w),
1083 (m), 1738 (m), 1710 (s), 1650 (m), 1572 (m), 1473 (m), 1438
(s), 1303 (m), 1248 (m), 1195 (s), 1153 (s), 1099 (s), 1067 (m), 1022
(s), 1000 (m), 886 (m), 844 (m), 803 (m), 745 (s), 703 (s), 688 (s),
608 (m); MS (EI, 70 eV): m/z (%)¼303 (13), 302 (Mþ, 70), 272 (11),
271 (61), 270 (21), 269 (100), 256 (18), 255 (49), 228 (17), 227
(13), 186 (11), 184 (15); HRMS (EI): calcd for C17H18O3S (Mþ):
302.09712, found: 302.09713.
(CH3), 27.1 (CH2), 52.0 (OCH3), 55.3 (OCH3), 114.4, 115.8, 127.1, 128.6
(CHAr), 129.7 (C), 130.0, 130.1 (CHAr), 134.1, 135.6, 138.1, 144.4, 160.5,
168.7 (C); IR (KBr, cmꢀ1): v¼3055 (w), 2999 (w), 2947 (w), 2835 (w),
1725 (s), 1590 (s), 1562 (s), 1459 (s), 1427 (m), 1399 (m), 1304 (m),
1266 (s), 1218 (s), 1187 (m), 1137 (s), 1090 (m), 1071 (m), 1047 (s), 995
(m), 958 (m), 849 (m), 773 (s), 677 (s), 608 (m); MS (EI, 70 eV): m/z
(%)¼338 (26), 337 (13), 336 (Mþ 70), 293 (29), 292 (17), 291 (83), 290
(27), 289 (100), 255 (17), 185 (10), 184 (18); HRMS (EI): calcd for
C17H17O3SCl (Mþ): 336.05814, found: 336.05741.
3.3. General procedure for the synthesis of
diaryl sulfides 5a–m
3.2.9. Methyl 6-methoxy-3,4-dimethyl-2-(4-ethylphenyl-sulfanyl)-
benzoate (3i). Starting with 2i (483 mg, 1.5 mmol) and 1a (364 mg,
2.25 mmol), 3i was isolated as a highly viscous colourless oil
To a dichloromethane solution (2 mL/mmol of 6) of 6 (1.5 mmol)
and of 1,1,3,3-tetramethoxypropane (1.0 mmol) was added TMSOTf
(0.1 mmol) at ꢀ78 ꢁC. The solution was allowed to warm to 20 ꢁC
within 20 h. To the solution was added a diluted aqueous solution
of HCl (15 mL). The organic and the aqueous layers were separated
and the latter was extracted with dichloromethane (3ꢂ15 mL). The
combined organic layers were dried (Na2SO4), filtered and the fil-
trate was concentrated in vacuo. The residue was purified by
chromatography.
(173 mg, 35%); 1H NMR (250 MHz, CDCl3):
d
¼1.10 (t, J¼7.6 Hz, 3H,
CH3), 2.11 (s, 3H, CH3), 2.25 (s, 3H, CH3), 2.48 (q, J¼7.6 Hz, 2H, CH2),
3.73 (s, 3H, OCH3), 3.75 (s, 3H, OCH3), 6.94–7.18 (m, 5H, ArH); 13C
NMR (63 MHz, CDCl3):
d
¼12.3 (CH3), 14.4 (CH3), 18.7 (CH3), 27.3
(CH2), 51.0 (OCH3), 54.6 (OCH3), 111.7 (CHAr), 126.6, 127.3 (2CHAr),
127.5,128.3,128.6,132.3,132.8,134.9,157.3,168.5 (C); IR (KBr, cmꢀ1):
v¼2962 (w), 2928 (w), 2872 (w), 2735 (w), 2664 (w),1083 (m),1738
(m), 1710 (s), 1650 (m), 1572 (m), 1473 (m), 1438 (s), 1303 (m), 1248
(m),1195 (s),1153 (s),1099 (s),1067 (m),1022 (s),1000 (m), 886 (m),
844 (m), 803 (m), 745 (s), 703 (s), 688 (s), 608 (m); MS (EI, 70 eV):
m/z (%)¼331 (20), 330 (Mþ, 98), 272 (11), 271 (61), 270 (21), 269
(100), 256 (18), 255 (49), 228 (17), 227 (13),186 (11),184 (15); HRMS
(EI): calcd for C19H22O3S (Mþ): 330.12842, found: 330.12824.
3.3.1. Methyl 2-(phenylsulfanyl)benzoate (5a). Starting with tetra-
methoxypropane (0.33 mL, 2.0 mmol), 2a (843 mg, 3.0 mmol),
TMSOTf (0.036 mL, 0.2 mmol) and CH2Cl2 (4 mL), 7a was isolated as
a highly viscous colourless oil (275 mg, 53%); 1H NMR (250 MHz,
CDCl3):
d
¼3.66 (s, 3H, OCH3), 6.75 (dd, 1H, 3J¼7.2, 4J¼1.87 Hz, ArH),
3.2.10. Methyl 2-(3-chlorophenylsulfanyl)-4-ethyl-6-methoxybenzoate
(3j). Starting with 2c (471 mg, 1.5 mmol) and 1b (396 mg,
2.25 mmol), 3j was isolated as a highly viscous colourless oil
7.06 (ddd, 1H, 3J¼7.2, 4J¼1.87, 5J¼0.92 Hz, ArH), 7.16 (m, 2H, ArH),
7.36 (m, 3H, ArH), 7.48 (m, 2H, ArH); 13C NMR (62 MHz, CDCl3):
d
¼52.1 (OCH3), 124.2 (ArCH), 126.7 (C), 127.4, 129.0 (ArCH), 129.7
(186 mg, 37%); 1H NMR (250 MHz, CDCl3):
d
¼1.55 (t, J¼7.6 Hz, 3H,
CH3), 2.56 (q, J¼7.6 Hz, 2H, CH2), 3.65 (s, 3H, OCH3), 3.76 (s, 3H,
OCH3), 6.58–7.23 (m, 6H, ArH); 13C NMR (63 MHz, CDCl3):
¼15.3
(2C, ArCH), 131.1, 132.2 (ArCH), 124.6 (C), 135.5 (2C, ArCH), 143.1,
~
166.8 (C); IR (neat):
n
¼3056 (w), 2948 (w), 1711 (s), 1585 (m), 1562
d
(m), 1433 (s), 1246 (s), 1189 (m), 1056 (s), 738 (s), 688 (s), 530 (m)
cmꢀ1; GC–MS (EI, 70 eV): m/z (%): 244 (100), 213 (76), 184 (55), 152
(16), 139 (10), 108 (8); HRMS (EI, 70 eV): calcd for C14H12O2S [Mþþ]:
244.05525, found: 244.05570.
(CH3), 27.1 (CH2), 52.0 (OCH3), 55.3 (OCH3), 114.4, 115.8, 127.1, 128.6
(CHAr), 129.7 (C), 130.0, 130.1 (CHAr), 134.1, 135.6, 138.1, 144.4, 160.5,
168.7 (C); IR (KBr, cmꢀ1): v¼3055 (w), 2999 (w), 2947 (w), 2835 (w),
1725 (s), 1590 (s), 1562 (s), 1459 (s), 1427 (m), 1399 (m), 1304 (m),
1266 (s), 1218 (s), 1187 (m), 1137 (s), 1090 (m), 1071 (m),1047 (s), 995
(m), 959 (m), 849 (m), 773 (s), 677 (s), 608 (m); MS (EI, 70 eV): m/z
(%)¼338 (26), 337 (13), 336 (Mþ 70), 293 (29), 292 (17), 291 (83), 290
(27), 289 (100), 255 (17), 185 (10), 184 (18); HRMS (EI): calcd for
C17H17O3SCl (Mþ): 336.05814, found: 336.057409.
3.3.2. Methyl 2-(4-fluorophenylsulfanyl)-benzoate (5b). Starting
with 1,1,3,3-tetramethoxypropane (0.25 mL, 1.5 mmol), 2f (447 mg,
1.5 mmol), and TMSOTf (0.02 mL, 0.12 mmol), and CH2Cl2 (7 mL),
5b was isolated as a highly viscous colourless oil (184 mg, 47%); 1H
NMR (250 MHz, CDCl3):
d
¼3.89 (s, 3H, OCH3), 6.69–7.89 (m, 8H,
ArH); 13C NMR (63 MHz, CDCl3):
d
¼52.0 (OCH3), 123.9 (CHAr), 126.3
3.2.11. Methyl 2-(4-methylphenylsulfanyl)-4-ethyl-6-methoxyben-
zoate (3k). Starting with 2d (441 mg, 1.5 mmol) and 1b (396 mg,
2.25 mmol), 3k was isolated as a highly viscous colourless oil
(CAr), 127.0 (CHAr), 128.6 (CAr), 130.6 (2C, CHAr), 131.0, 132.2 (CHAr),
~
135.7 (2C, CHAr), 139.4, 143.9 (CAr), 166.8 (C); IR (neat):
n
¼3056 (w),
2948 (w), 1711 (s), 1585 (m), 1562 (m), 1433 (s), 1246 (s), 1189 (m),
1056 (s), 738 (s), 688 (s), 530 (m) cmꢀ1; GC–MS (EI, 70 eV): m/z (%):
263 (17), 262 (Mþ 100), 232 (12), 231 (77), 228 (14), 227 (87), 184
(55), 152 (16), 139 (10), 108 (8); HRMS (EI): calcd for C14H11O2FS
[Mþ]: 262.04583, found: 262.046008.
(180 mg, 38%); 1H NMR (250 MHz, CDCl3):
d
¼1.14 (t, J¼7.6 Hz, 3H,
CH3), 2.26 (s, 3H, CH3), 2.57 (q, J¼7.6 Hz, 2H, CH2), 3.59 (s, 3H,
OCH3), 3.81 (s, 3H, OCH3), 6.41–7.25 (m, 6H, ArH); 13C NMR
(63 MHz, CDCl3):
d
¼14.3 (CH3), 20.1 (CH3), 26.1 (CH2), 50.9 (OCH3),
54.1 (OCH3), 111.8, 112.6 (CHAr), 126.0 (C), 128.8, 131.7 (2CHAr),
132.3, 136.1, 136.9, 143.3, 159.3, 167.9 (C); IR (KBr, cmꢀ1): v¼3055
(w), 2999 (w), 2947 (w), 2835 (w), 1725 (s), 1590 (s), 1562 (s), 1459
(s), 1427 (m), 1399 (m), 1304 (m), 1266 (s), 1218 (s), 1187 (m), 1137
(s), 1090 (m), 1071 (m), 1047 (s), 995 (m), 959 (m), 849 (m), 773 (s),
3.3.3. Methyl 2-(m-tolylsulfanyl)-benzoate (5c). Starting with
1,1,3,3-tetramethoxypropane (0.25 mL, 1.5 mmol), 2b (441 mg,
1.5 mmol), and TMSOTf (0.02 mL, 0.12 mmol), and CH2Cl2 (7 mL), 5c
was isolated as a highly viscous colourless oil (208 mg, 54%); 1H

M. Imran et al. / Tetrahedron 65 (2009) 8794–8801
8799
NMR (250 MHz, CDCl3):
d
¼2.33 (s, 3H, CH3), 3.91 (s, 3H, OCH3),
HRMS (EI): calcd for
272.086163.
C
16H16O2S [Mþ]: 272.08655, found:
6.72–7.41 (m, 8H, ArH); 13C NMR (63 MHz, CDCl3):
d
¼21.3 (CH3),
52.0 (OCH3), 123.9 (CHAr), 126.3 (CAr), 127.0 (CHAr), 128.6 (CAr), 130.6
(2C, CHAr), 131.0, 132.2 (CHAr), 135.7 (2C, CHAr), 139.4, 143.9 (CAr),
3.3.8. Methyl 2-(cyclohexa-1,5-dienylsufanyl)-3-methyl-benzoate (5h).
Starting with 1,1,3,3-tetramethoxypropane (0.25 mL, 1.5 mmol), 2h
(441 mg, 1.5 mmol), and TMSOTf (0.02 mL, 0.12 mmol), and CH2Cl2
(7 mL), 5h was isolated as a highly viscous colourless oil (193 mg,
~
166.8 (C); IR (neat):
n
¼3056 (w), 2948 (w), 1711 (s), 1585 (m), 1562
(m), 1433 (s), 1246 (s), 1189 (m), 1056 (s), 738 (s), 688 (s), 530 (m)
cmꢀ1; GC–MS (EI, 70 eV): m/z (%): 259 (34), 258 (Mþ 100), 228 (14),
227 (87), 184 (55), 152 (16), 139 (10), 108 (8); HRMS (EI): calcd for
C15H14O2S [Mþ]: 258.05525, found: 258.05570.
50%); 1H NMR (250 MHz, CDCl3):
d
¼2.30 (s, 3H, CH3), 3.86 (s, 3H,
OCH3), 7.12–7.74 (m, 8H, ArH); 13C NMR (63 MHz, CDCl3):
d
¼21.2
(CH3), 52.3 (OCH3), 124.5 (CAr), 125.5, 126.4 (CHAr), 127.5, 128.8 (2C,
3.3.4. Methyl 2-(3-chlorophenylsulfanyl)-benzoate (5d). Starting with
1,1,3,3-tetramethoxypropane (0.25 mL, 1.5 mmol), 2c (471 mg,
1.5 mmol), and TMSOTf (0.02 mL, 0.12 mmol), and CH2Cl2 (7 mL), 5d
was isolated as a highly viscous colourless oil (212 mg, 51%); 1H NMR
CHAr), 129.1, 132.9 (CHAr), 136.3, 138.4, 143.0 (CAr), 167.9 (C); IR (neat):
~
n
¼3056 (w), 2948 (w), 1711 (s), 1585 (m), 1562 (m), 1433 (s), 1246 (s),
1189 (m), 1056 (s), 738 (s), 688 (s), 530 (m) cmꢀ1; GC–MS (EI, 70 eV):
m/z (%): 259 (17), 258 (Mþ 100), 227 (42), 226 (39), 225 (55), 184 (55),
152 (16), 139 (10), 108 (8); HRMS (EI): calcd for C15H14O2S [Mþ]:
258.07090, found: 258.070812.
(250 MHz, CDCl3):
d
¼3.87 (s, 3H, OCH3), 6.77–7.92 (m, 8H, ArH); 13
C
NMR (63 MHz, CDCl3):
(CHAr), 128.6 (CAr), 130.6 (2C, CHAr), 131.0, 132.2 (CHAr), 135.7 (2C,
d
¼51.2 (OCH3), 123.9 (CHAr), 126.3 (CAr), 127.0
~
CHAr), 139.4, 143.9 (CAr), 166.8 (C); IR (neat):
n
¼3056 (w), 2948 (w),
3.3.9. Methyl 2-(4-fluorocyclohexa-1,5-dienylsulfanyl)-3-methyl-ben-
zoate (5i). Starting with 1,1,3,3-tetramethoxypropane (0.25 mL,
1.5 mmol), 2l (468 mg, 1.5 mmol), and TMSOTf (0.02 mL, 0.12
mmol), and CH2Cl2 (7 mL), 5i was isolated as a highly viscous col-
1711 (s),1585 (m), 1562 (m),1432 (s),1246 (s),1189 (m),1056 (s), 738
(s), 688 (s), 530 (m) cmꢀ1; GC–MS (EI, 70 eV): m/z (%): 280 (31), 279
(12), 278 (Mþ 100), 249 (18), 247 (54), 227 (87), 184 (55), 152 (16),
139 (10), 108 (8); HRMS (EI): calcd for C14H11O2ClS [Mþ]: 278.01628,
found: 278.016068.
ourless oil (182 mg, 44%); 1H NMR (250 MHz, CDCl3):
d
¼2.25 (s, 3H,
CH3), 3.83 (s, 3H, OCH3), 6.72–7.54 (m, 7H, ArH); 13C NMR (63 MHz,
CDCl3):
d
¼20.2 (CH3), 51.3 (OCH3), 114.8, 115.1 (CHAr), 124.5 (CAr),
3.3.5. Methyl 2-(p-tolylsulfanyl)-benzoate (5e). Starting with
1,1,3,3-tetramethoxypropane (0.25 mL, 1.5 mmol), 2d (441 mg,
1.5 mmol), and TMSOTf (0.02 mL, 0.12 mmol), and CH2Cl2 (7 mL), 5e
was isolated as a highly viscous colourless oil (205 mg, 53%); 1H
125.4,128.0,128.7,128.8 (CHAr),129.1,129.9 (CAr),132.0 (CHAr),143.1,
~
144.2 (CAr), 167.9 (C); IR (neat):
n
¼3056 (w), 2948 (w), 1711 (s), 1585
(m), 1562 (m), 1433 (s), 1246 (s), 1189 (m), 1056 (s), 738 (s), 688 (s),
530 (m) cmꢀ1; GC–MS (EI, 70 eV): m/z (%): 277 (16), 276 (Mþ 100),
345 (40), 244 (24), 243 (60), 225 (55),184 (55),152 (16),139 (10),108
(8); HRMS (EI): calcd for C15H13O2FS [Mþ]: 276.06148, found:
276.061274.
NMR (250 MHz, CDCl3):
d
¼2.34 (s, 3H, CH3), 3.90 (s, 3H, OCH3),
6.72–7.94 (m, 8H, ArH); 13C NMR (63 MHz, CDCl3):
d
¼21.3 (CH3),
52.1 (OCH3), 123.9 (CHAr), 126.3 (CAr), 127.0 (CHAr), 128.6 (CAr), 130.6
(2C, CHAr), 131.0, 132.2 (CHAr), 135.7 (2C, CHAr), 139.4, 143.9 (CAr),
~
166.8 (C); IR (neat):
n
¼3056 (w), 2948 (w), 1711 (s), 1585 (m), 1562
3.3.10. Methyl (3-ethyl-2-phenylsulfanyl)-benzoate (5j). Starting with
1,1,3,3-tetramethoxypropane (0.25 mL, 1.5 mmol), 2m (462 mg,
1.5 mmol), and TMSOTf (0.02 mL, 0.12 mmol), and CH2Cl2 (7 mL), 5j
was isolated as a highly viscous colourless oil (204 mg, 50%); 1H NMR
(m), 1433 (s), 1246 (s), 1189 (m), 1056 (s), 738 (s), 688 (s), 530 (m)
cmꢀ1; GC–MS (EI, 70 eV): m/z (%): 259 (34), 258 (Mþ 100), 228 (14),
227 (87), 184 (55), 152 (16), 139 (10), 108 (8); HRMS (EI): calcd for
C15H14O2S [Mþ]: 258.05525, found: 258.05570.
(250 MHz, CDCl3):
d
¼1.06 (t, J¼7.5 Hz, 3H, CH2CH3), 2.72 (q,
J¼7.5 Hz, 2H, CH2CH3), 3.66 (s, 3H, OCH3), 6.98–7.34 (m, 8H, ArH); 13
C
3.3.6. Methyl 2-(naphth-2-ylsulfanyl)-benzoate (5f). Starting with
1,1,3,3-tetramethoxypropane (0.25 mL, 1.5 mmol), 2j (495 mg,
1.5 mmol), and TMSOTf (0.02 mL, 0.12 mmol), and CH2Cl2 (7 mL),
5f was isolated as a highly viscous colourless oil (145 mg, 33%);
NMR (63 MHz, CDCl3):
(CHAr), 126.3 (CAr), 126.4 (CHAr), 127.3, 128.8 (2C, CHAr), 129.0 (CAr),
d¼14.9 (CH3), 27.3 (CH2), 52.2 (OCH3), 125.4
~
129.2, 131.1 (CHAr),139.4,143.9 (CAr),166.8 (C); IR (neat):
n
¼3056 (w),
2948 (w), 1711 (s), 1585 (m), 1562 (m), 1433 (s), 1246 (s), 1189 (m),
1056 (s), 738 (s), 688 (s), 530 (m) cmꢀ1; GC–MS (EI, 70 eV): m/z (%):
273 (18), 272 (Mþ 100), 228 (14), 227 (87),184 (55),152 (16),139 (10),
108 (8); HRMS (EI): calcd for C16H16O2S [Mþ]: 272.05025, found:
258.050701.
1H NMR (250 MHz, CDCl3):
11H, ArH); 13C NMR (63 MHz, CDCl3):
d
¼3.91 (s, 3H, OCH3), 6.72–8.01 (m,
d
¼52.2 (OCH3), 124.4, 126.7
(CHAr), 126.8 (CAr), 127.0, 127.7, 127.8, 127.9, 129.4 (CHAr), 129.9
(CAr), 131.0, 131.8, 132.3 (CHAr), 133.2, 13.9 (CAr), 135.2 (CHAr),
~
143.0 (CAr), 166.8 (C); IR (neat):
n
¼3055 (w), 2948 (w), 1711 (s),
1585 (m), 1562 (m), 1433 (s), 1246 (s), 1189 (m), 1056 (s), 738 (s),
688 (s), 530 (m) cmꢀ1; GC–MS (EI, 70 eV): m/z (%): 296 (17), 294
(Mþ 100), 228 (14), 227 (87), 184 (55), 152 (16), 139 (10), 108 (8);
HRMS (EI): calcd for C18H14O2S [Mþ]: 294.05525, found:
294.05570.
3.3.11. Methyl 2-(4-ethylcyclohexa-1,5-dienylsulfanyl)-benzoate (5k).
Starting with 1,1,3,3-tetramethoxypropane (0.25 mL, 1.5 mmol), 2e
(462 mg, 1.5 mmol), and TMSOTf (0.02 mL, 0.12 mmol), and CH2Cl2
(7 mL), 5k was isolated as a highly viscous colourless oil (224 mg,
55%); 1H NMR (250 MHz, CDCl3):
d
¼1.11 (t, J¼7.5 Hz, 3H, CH2CH3),
2.71 (q, J¼7.5 Hz, 2H, CH2CH3), 3.86 (s, 3H, OCH3), 6.73–7.94 (m, 8H,
ArH); 13C NMR (63 MHz, CDCl3):
3.3.7. Methyl
3-methyl-2-(4-methylcyclohexa-1,5-dienylsulfanyl)-
d
¼15.3 (CH3), 28.5 (CH2), 52.1
benzoate (5g). Starting with 1,1,3,3-tetramethoxypropane (0.25 mL,
1.5 mmol), 2k (462 mg, 1.5 mmol), and TMSOTf (0.02 mL,
0.12 mmol), and CH2Cl2 (7 mL), 5g was isolated as a highly viscous
(OCH3), 124.4 (CHAr), 126.3 (CAr), 126.6 (CHAr), 128.5 (2C, CHAr), 129.0
(CAr), 130.5, 132.2 (CHAr),135.8 (2C, CHAr), 139.4, 143.9 (CAr),166.8 (C);
~
IR (neat):
n
¼3056 (w), 2948 (w), 1711 (s), 1585 (m), 1562 (m), 1433
colourless oil (187 mg, 46%); 1H NMR (250 MHz, CDCl3):
d
¼2.12 (s,
3H, CH3), 2.25 (s, 3H, CH3), 3.78 (s, 3H, OCH3), 6.82–7.44 (m, 7H,
ArH); 13C NMR (63 MHz, CDCl3):
(s),1246 (s),1189 (m),1056 (s), 738 (s), 688 (s), 530 (m) cmꢀ1; GC–MS
(EI, 70 eV): m/z (%): 273 (19), 272 (Mþ 100), 228 (14), 227 (87), 184
(55), 152 (16), 139 (10), 108 (8); HRMS (EI): calcd for C16H16O2S [Mþ]:
272.05025, found: 258.050701.
d
¼19.9, 20.1 (CH3), 51.3 (OCH3),
125.2 (CHAr), 126.9 (2C, CHAr), 127.5 (CHAr), 128.7 (2C, CHAr), 131.8
(CHAr), 136.3, 138.4, 143.0, 144.6, 144.9 (CAr), 167.9 (C); IR (neat):
~
n
¼3055 (w), 2948 (w), 1711 (s), 1585 (m), 1562 (m), 1433 (s), 1246
3.3.12. Methyl 2-(4-ethylcyclohexa-1,5-dienylsulfanyl)-4-methyl-ben-
zoate (5l). Starting with 1,1,3,3-tetramethoxypropane (0.25 mL,
1.5 mmol), 2i (483 mg, 1.5 mmol), and TMSOTf (0.02 mL,
0.12 mmol), and CH2Cl2 (7 mL), 5l was isolated as a highly viscous
(s), 1189 (m), 1056 (s), 738 (s), 688 (s), 530 (m) cmꢀ1; GC–MS (EI,
70 eV): m/z (%): 273 (18), 272 (Mþ 100), 241 (29), 240 (22), 239 (15),
227 (42), 226 (39), 225 (55), 184 (55), 152 (16), 139 (10), 108 (8);

8800
M. Imran et al. / Tetrahedron 65 (2009) 8794–8801
colourless oil (193 mg, 45%); 1H NMR (250 MHz, CDCl3):
d¼1.09 (t,
1437 (s), 1380 (w), 1266 (s), 1240 (s), 1188 (m), 1152 (m), 1105 (s),
1066 (s), 1023 (m), 954 (m), 738 (s), 688 (s); MS (EI, 70 eV): m/z
(%)¼319 (20), 318 (Mþ 100), 287 (33), 272 (16), 271 (25), 212 (16),
211 (14), 195 (17), 63 (7); HRMS (EI): calcd for C17H18O2S2 (Mþ):
318.07427, found: 318.07489.
J¼7.5 Hz, 3H, CH2CH3), 2.28 (s, 3H, CH3), 2.42 (q, J¼7.5 Hz, 2H,
CH2CH3), 3.78 (s, 3H, OCH3), 6.90–7.34 (m, 7H, ArH); 13C NMR
(63 MHz, CDCl3):
(OCH3),125.2 (CHAr),126.9,127.4 (2C, CHAr),127.6 (CHAr),129.7 (CAr),
d
¼14.4 (CH2CH3), 20.3 (CH3), 27.3 (CH2CH3), 51.3
131.1 (CHAr), 132.7, 138.2, 140.8, 142.8 (CAr), 168.0 (C); IR (neat):
~
n
¼3056 (w), 2948 (w),1711 (s),1585 (m),1562 (m),1433 (s),1246 (s),
3.4.3. Methyl 4-chloro-2-methylsulfanyl-6-(4-tolylsulfanyl)-benzoate
(7c). Starting with 2g (472 mg, 1.5 mmol), 6 (243 mg, 1.5 mmol),
TiCl4 (0.25 mL, 2.25 mmol) and CH2Cl2 (9 mL), 7c was isolated as
a highly viscous oil (244 mg, 45%); 1H NMR (250 MHz, CDCl3):
1189 (m),1056 (s), 738 (s), 688 (s), 530 (m) cmꢀ1; GC–MS (EI, 70 eV):
m/z (%): 287 (18), 286 (Mþ 100), 271 (17), 227 (87),184 (55),152 (16),
139 (10), 108 (8); HRMS (EI): calcd for C17H18O2S [Mþ]: 286.10220,
found: 286.102313.
d
¼2.22 (s, 3H, CH3), 2.39 (s, 3H, SCH3), 3.85 (s, 3H, OCH3), 6.80–7.30
(m, 6H, Ar); 13C NMR (63 MHz, CDCl3):
d
¼21.1 (CH3), 21.3 (SMe),
3.3.13. Methyl 2-(3-chlorocyclohexa-1,5-dienylsulfanyl)-3-methyl-ben-
zoate (5m). Starting with 1,1,3,3-tetramethoxypropane (0.25 mL,
1.5 mmol), 2n (492 mg,1.5 mmol), and TMSOTf (0.02 mL, 0.12 mmol),
and CH2Cl2 (7 mL), 5m was isolated as a highly viscous colourless oil
52.3 (OMe), 127.4, 128.3, 128.8, 129.0, 130.2, 132.2 (CHAr), 133.6,
134.6, 134.7, 136.8, 139.0, 140.5 (CAr), 167.7 (CO); IR (KBr, cmꢀ1):
v¼3055 (w), 2994 (w), 2948 (w), 2927 (w), 2857 (w), 1726 (s), 1608
(m), 1581 (m), 1475 (m), 1449 (s), 1437 (s), 1380 (w), 1266 (s), 1240
(s), 1188 (m), 1152 (m), 1105 (s), 1066 (s), 1023 (m), 957 (m), 738 (s),
688 (s); MS (EI, 70 eV): m/z (%)¼340 (24), 338 (Mþ, 71), 287 (33),
272 (16), 271 (25), 212 (16), 211 (14), 195 (17), 63 (7); HRMS (EI):
calcd for C16H15O2S2Cl (Mþ): 338.3496, found: 338.33908.
(210 mg, 48%); 1H NMR (250 MHz, CDCl3):
d¼2.33 (s, 3H, CH3), 3.85
(s, 3H, OCH3), 6.82–7.53 (m, 7H, ArH); 13C NMR (63 MHz, CDCl3):
d
¼20.2 (CH3), 51.3 (OCH3), 124.5 (CAr), 125.5 (CHAr), 126.5 (CAr), 127.6,
128.0 (2C, CHAr),128.3,132.0 (CHAr),136.3,138.4,143.0 (CAr),167.9 (C);
~
IR (neat):
n
¼3056 (w), 2948 (w), 1711 (s),1585 (m), 1562 (m), 1433 (s),
1246 (s), 1189 (m), 1056 (s), 738 (s), 688 (s), 530 (m) cmꢀ1; GC–MS (EI,
70 eV): m/z (%): 294 (39), 293 (17), 292 (Mþ 100), 261 (35), 260 (15),
227 (42), 226 (39), 225 (55), 184 (55), 152 (16), 139 (10), 108 (8);
HRMS (EI): calcd for C15H13O2ClS [Mþ]: 292.03193, found:
292.032066.
3.4.4. Methyl 3,4-dimethyl-6-methylsulfanyl-2-phenylsulfanyl-ben-
zoate (7d). Starting with 2h (441 mg, 1.5 mmol),
6 (243 mg,
1.5 mmol), TiCl4 (0.25 mL, 2.25 mmol) and CH2Cl2 (9 mL), 7d was
isolated as a highly viscous oil (190 mg, 40%); 1H NMR (250 MHz,
CDCl3):
(s, 3H, OCH3), 6.91–7.30 (m, 6H, Ar); 13C NMR (63 MHz, CDCl3):
¼21.0 (CH3), 21.1 (CH3), 21.3 (SMe), 52.3 (OMe), 127.4, 128.3, 128.8,
d
¼2.21 (s, 3H, CH3), 2.22 (s, 3H, CH3), 2.39 (s, 3H, SCH3), 3.85
3.4. General procedure for the synthesis
of diaryl sulfides 7a–e
d
129.0, 130.2, 132.2 (CHAr), 133.6, 134.6, 134.7, 136.8, 139.0, 140.5
(CAr), 167.8 (CO); IR (KBr, cmꢀ1): v¼3055 (w), 2994 (w), 2948 (w),
2927 (w), 2857 (w), 1726 (s), 1608 (m), 1581 (m), 1475 (m), 1449 (s),
1437 (s), 1380 (w), 1266 (s), 1240 (s), 1188 (m), 1152 (m), 1105 (s),
1066 (s), 1023 (m), 957 (m), 738 (s), 688 (s); MS (EI, 70 eV): m/z
(%)¼319 (21), 318 (Mþ 100), 287 (33), 272 (16), 271 (25), 212 (16),
211 (14), 195 (17), 63 (7); HRMS (EI): calcd for C17H18O2S2 (Mþ):
318.07427, found: 318.075053.
To a dichloromethane solution (6 mL/mmol of 6) of 2 (1.5 mmol)
and of 6 (1.5 mmol) was added TiCl4 (2.25 mmol) at ꢀ78 ꢁC. The
solution was allowed to warm to 20 ꢁC within 20 h. To the solution
was added a hydrochloric acid (10%, 25 mL). The organic and the
aqueous layers were separated and the latter was extracted with
dichloromethane (3ꢂ20 mL). The combined organic layers were
dried (Na2SO4), filtered, and the filtrate was concentrated in vacuo
and the residue was purified by chromatography (silica gel, EtOAc/
n-heptane¼1:9).
3.4.5. Methyl 3,4-dimethyl-6-methylsulfanyl-2-(4-tolylsulfanyl)-ben-
zoate (7e). Starting with 2k (462 mg, 1.5 mmol),
6 (243 mg,
1.5 mmol), TiCl4 (0.25 mL, 2.25 mmol) and CH2Cl2 (9 mL), 7e was
3.4.1. Methyl 4-methyl-2-methylsulfanyl-6-(4-tolylsulfanyl)-benzo-
isolated as a highly viscous oil (184 mg, 37%); 1H NMR (250 MHz,
ate (7a). Starting with 2d (441 mg, 1.5 mmol),
6
(243 mg,
CDCl3):
(s, 3H, OCH3), 6.91–7.30 (m, 5H, Ar); 13C NMR (63 MHz, CDCl3):
¼21.0 (CH3), 21.0 (CH3), 21.3 (SMe), 52.3 (OMe), 127.3, 128.6, 128.9,
d
¼2.20 (s, 3H, CH3), 2.22 (s, 3H, CH3), 2.39 (s, 3H, SCH3), 3.85
1.5 mmol), TiCl4 (0.25 mL, 2.25 mmol) and CH2Cl2 (9 mL), 7a was
isolated as a highly viscous oil (262 mg, 55%); 1H NMR (250 MHz,
d
CDCl3):
(s, 3H, OCH3), 6.80–7.19 (m, 6H, Ar); 13C NMR (63 MHz, CDCl3):
¼17.4 (CH3), 21.2 (CH3), 21.3 (Sme), 52.2 (Ome), 127.4, 128.3, 128.8,
d¼2.21 (s, 3H, CH3), 2.23 (s, 3H, CH3), 2.39 (s, 3H, SCH3), 3.82
129.0, 130.2, 132.2 (CHAr), 133.6, 134.6, 134.7, 136.8, 139.0, 140.5
(CAr), 167.8 (CO); IR (KBr, cmꢀ1): v¼3055 (w), 2994 (w), 2948 (w),
2927 (w), 2857 (w), 1726 (s), 1608 (m), 1581 (m), 1475 (m), 1449 (s),
1437 (s), 1380 (w), 1266 (s), 1240 (s), 1188 (m), 1152 (m), 1105 (s),
1066 (s), 1023 (m), 957 (m), 738 (s), 688 (s); MS (EI, 70 eV): m/z
(%)¼333 (21), 332 (Mþ 100), 287 (33), 272 (16), 271 (25), 212 (16),
211 (14), 195 (17), 63 (7); HRMS (EI): calcd for C17H18O2S2 (Mþ):
332.08992, found: 332.090382.
d
129.0, 130.2, 132.2 (CHAr), 133.6, 134.6, 134.7, 136.8, 139.0, 140.5
(CAr), 167.7 (CO); IR (KBr, cmꢀ1): v¼3056 (w), 2994 (w), 2948 (w),
2927 (w), 2857 (w), 1727 (s), 1606 (m), 1581 (m), 1476 (m), 1449 (s),
1437 (s), 1380 (w), 1266 (s), 1240 (s), 1188 (m), 1152 (m), 1105 (s),
1066 (s), 1023 (m), 954 (m), 738 (s), 688 (s); MS (EI, 70 eV): m/z
(%)¼319 (20), 318 (Mþ 100), 287 (33), 272 (16), 271 (25), 212 (16),
211 (16), 195 (17), 63 (3); HRMS (EI): calcd for C17H18O2S2 (Mþ):
318.07427, found: 318.07489.
Acknowledgements
Financial support by the State of Pakistan (HEC scholarships for
I.I. and N.R.) and by the State of Mecklenburg-Vorpommern
(scholarship for M.I.) is gratefully acknowledged.
3.4.2. Methyl 3-methyl-2-methylsulfanyl-6-(4-tolylsulfanyl)-benzo-
ate (7b). Starting with 2b (441 mg, 1.5 mmol),
6 (243 mg,
1.5 mmol), TiCl4 (0.25 mL, 2.25 mmol) and CH2Cl2 (9 mL), 7b was
isolated as a highly viscous oil (248 mg, 52%); 1H NMR (250 MHz,
References and notes
CDCl3):
d
¼2.22 (s, 3H, CH3), 2.24 (s, 3H, CH3), 2.39 (s, 3H, SCH3), 3.82
(s, 3H, OCH3), 6.80–7.20 (m, 6H, Ar); 13C NMR (63 MHz, CDCl3):
1. (a) Behar, V.; Danishefsky, S. J. J. Am. Chem. Soc. 1993, 115, 7017; (b) Toste, F. D.;
Still, I. W. J. J. Am. Chem. Soc. 1995, 117, 7261; (c) Davidson, B. S.; Molinski, T. F.;
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Sakata, M.; Sagai, M.; Seki, K.-i. Biol. Pharm. Bull. 2002, 25, 145; (e) Davis, R. A.;
Sandoval, I. T.; Concepcion, G. P.; Moreira da Rocha, R.; Ireland, C. M.
d
¼17.4 (CH3), 21.1 (CH3), 21.3 (SMe), 52.2 (Ome), 127.4, 128.3, 128.8,
129.0, 130.2, 132.2 (CHAr), 133.6, 134.6, 134.7, 136.8, 139.0, 140.5
(CAr), 167.7 (CO); IR (KBr, cmꢀ1): v¼3055 (w), 2994 (w), 2948 (w),
2927 (w), 2857 (w), 1726 (s), 1606 (m), 1581 (m), 1476 (m), 1449 (s),

M. Imran et al. / Tetrahedron 65 (2009) 8794–8801
8801
Tetrahedron 2003, 59, 2855; (f) Liu, H.; Fujiwara, T.; Nishikawa, T.; Mishima, Y.;
Nagai, H.; Shida, T.; Tachibana, K.; Kobayashi, H.; Mangindaan, R. E. P.; Namikoshi,
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16. (a) Wilson, B. D. Synthesis 1992, 3, 283; (b) Heilbron, I.; Jones, E. R. H.; Julia, M.
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2331.
´
´
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19. Potts, K. T.; Winslow, P. A. Synthesis 1987, 839.