Regioselective synthesis of 2-(arylthio)benzoates by the first catalytic [3+3] cyclocondensations of 3-(arylthio)-1-(trimethylsilyloxy)-1,3-butadienes with 1,1,3,3-tetramethoxypropane

Article abstract of DOI:10.1055/s-0028-1083516

2-(Arylthio)benzoates were regioselectively prepared by the first catalytic [3+3] cyclizations of 3-(arylthio)-1-(trimethylsilyloxy)-1,3-butadienes with 1,1,3,3-tetramethoxypropane.

Full text of DOI:10.1055/s-0028-1083516

2708
LETTER
Regioselective Synthesis of 2-(Arylthio)benzoates by the First Catalytic [3+3]
Cyclocondensations of 3-(Arylthio)-1-(trimethylsilyloxy)-1,3-butadienes with
1,1,3,3-Tetramethoxypropane
R
egioselective Synthes
u
is of 2-(Aryl
h
thio)benzoat
a
es mmad Imran,a Inam Iqbal,a Nasir Rasool,a Muhammad A. Rashid,a Peter Langer*a,b
a
b
Received 13 July 2008
trimethylsilyl trifluoromethanesulfonate (TMSOTf) as
the catalyst.14
Abstract: 2-(Arylthio)benzoates were regioselectively prepared by
the first catalytic [3+3] cyclizations of 3-(arylthio)-1-(trimethylsilyl-
oxy)-1,3-butadienes with 1,1,3,3-tetramethoxypropane.
Chan et al. reported the synthesis of 2-(phenylthio)ben-
zoates by TiCl4-mediated [3+3] cyclization of 3-(sily-
loxy)-2-en-1-ones with 3-(arylthio)-1-(trimethylsilyl-
oxy)-1,3-butadienes.15 Recently, we have studied the
TiCl4-mediated domino [3+3]-cyclization–homo-Michael
reaction of 3-(arylthio)-1-(trimethylsilyloxy)-1,3-buta-
dienes with 1,1-diacylcyclopropanes.16 Herein, we com-
municate a convenient synthesis of 2-(arylthio)benzoates
by what are, to the best of our knowledge, the first formal
[3+3] cyclocondensations of 3-(arylthio)-1-(trimethylsi-
lyloxy)-1,3-butadienes with 1,1,3,3-tetramethoxypro-
pane. It is important to note that these reactions can be
carried out using catalytic amounts of TMSOTf. In con-
trast to the C–S coupling reactions outlined above, our
method relies on the assembly of one of the two arene
moieties.
Key Words: arenes, cyclizations, diaryl sulfides, regioselectivity,
silyl enol ethers
Diaryl sulfides are pharmacologically relevant com-
pounds, which occur in a number of natural products.
Prominent examples include the lissoclibadins, diben-
zothiophenes, cyclic sulfides, varacins (lissoclinotoxins),
and related natural products.1 Classic syntheses of diaryl
sulfides include, for example, reactions of arenes with
sulfur2 or sulfur dichloride,3 condensations of Grignard or
organolithium reagents with chlorophenyl-sulfides,4 or
base-mediated reactions of thiophenols with chloroare-
nes.5 The competing formation of polysulfides and low re-
gioselectivities are severe drawbacks of these methods. In
contrast, transition-metal-catalyzed6 and metal-free7 car-
bon–sulfur coupling reactions allow the synthesis of diar-
yl sulfides under relatively mild conditions. However, the
scope of this approach is limited by the fact that reactions
of sterically encumbered substrates are often difficult or
not possible at all. In addition, the synthesis of the starting
materials, substituted aryl halides or triflates, can be a dif-
ficult task.
The reaction of b-ketoesters 1a–c with various thiophe-
nols gave the 3-(arylthio)alkanoates 2a–l (Scheme 1,
Table 1). Deprotonation of 2a–l (LDA) and subsequent
addition of TMSCl afforded the novel 3-(arylthio)-1-
(silyloxy)-1,3-butadienes 3a–l in very good yields.
O
O
SAr
O
ArSH
i
R
R
OMe
OMe
A strategy to circumvent these problems relies on the ap-
plication of a building-block approach using appropriate
sulfur-containing substrates in cyclization reactions. Dia-
ryl sulfides have been prepared by cobalt(I)-catalyzed
[4+2] cycloaddition of alkynyl sulfides with 1,3-buta-
dienes.8 Recently, we studied9 the synthesis of 3- and 5-
(arylthio)salicylates by TiCl4-mediated [3+3] cycli-
zations10 of 1,3-bis(silyloxy)-1,3-butadienes11 with 3-(si-
lyloxy)-2-en-1-ones, a method first developed12 by
Chan and coworkers. The TiCl4-mediated cycloconden-
sation of 1,3-bis(silyloxy)-1,3-butadienes with 1,1,3,3-
tetramethoxypropane and 2-alkyl-1,1,3,3-tetraethoxypro-
panes has also been reported.12,13 Recently, we have de-
veloped a catalytic variant of this reaction using
1a–c
2a–l
ii
OTMS
OMe
SAr
R
3a–l
Scheme 1 Synthesis of 3a–l (for substituents and yields, see Table
1). Reagents and conditions: (i) P4O10, CH2Cl2, 20 °C, 18 h; (ii) 1. LDA,
THF, –78 °C, 1 h; 2. TMSCl, –78 to 20 °C, 14 h.
The reaction of 3-(phenylthio)-1-(silyloxy)-1,3-butadiene
3a with 1,1,3,3-tetramethoxypropane (4), in the presence
of catalytic amounts of TMSOTf, afforded the 2-(phe-
nylthio)benzoate 5a (Scheme 2).17 The best yields were
obtained when 0.1 equivalents of Lewis acid were used.
The use of 0.2 or 1.0 equivalents of TMSOTf did not re-
sult in an increase of the yield. The yields decreased when
less than 0.1 equivalents of Lewis acid were employed.
The use of 1.0 equivalent of TiCl4 proved to be possible,
SYNLETT 2008, No. 17, pp 2708–2710
x
x
.x
x
.2
0
0
8
Advanced online publication: 01.10.2008
DOI: 10.1055/s-0028-1083516; Art ID: G25508ST
© Georg Thieme Verlag Stuttgart · New York

LETTER
Regioselective Synthesis of 2-(Arylthio)benzoates
2709
use of tetraethoxypropane rather than 4 proved to be un-
successful. The use of trifluoroacetic acid or triflic acid
(rather than TMSOTf) failed to give the desired product.
Table 1 Synthesis of 5a–l
2, 3, 5
R
Ar
Yield of 2 Yield of 3 Yield of 5
(%)a
84
85
82
80
87
80
75
81
82
34
84
83
(%)a
83
88
82
80
84
86
78
87
85
82
83
84
(%)a
53
53
54
47
51
51
33
50
46
44
50
52
The formation of 5a can be explained by TMSOTf-cata-
lyzed formation of oxonium cation A, attack of the termi-
nal carbon atom of 3a onto A to give intermediate B,
TMSOTf-catalyzed formation of oxonium cation C, cy-
clization to give intermediate D, and subsequent aromati-
zation by extrusion of methanol. The suggested
mechanism has not been experimentally proved.
a
b
c
d
e
f
H
Ph
H
4-MeC6H4
3-MeC6H4
4-FC6H4
4-ClC6H4
3-ClC6H4
2-Naph
Ph
H
H
H
The cyclization of dienes 3a–l with 4 afforded the 2-(aryl-
thio)benzoates 5a–l in moderate yields (Scheme 3,
Table 1). Comparable yields were obtained for products
5d–f, which are derived from dienes containing an elec-
tron-withdrawing halogen atom located at the arylthio
group, and for products 5a–c, which are derived from
dienes containing an electron-rich arylthio group. In addi-
tion, no decrease of the yield was observed for products
5h–l derived from dienes 3h–l containing a methyl or ethyl
group located at carbon atom C4 of the diene, compared
to products 5a–g derived from unsubstituted dienes 3a–g.
H
g
h
i
H
Me
Me
Me
Et
Et
4-MeC6H4
4-FC6H4
Ph
j
k
l
4-MeC6H4
a Isolated yields.
SAr OTMS
R
OMe
PhS
OTMS
SAr
O
O
SPh
3a–l
R
OMe
OMe
OMe
OMe
i
OMe
3a
OMe
+
MeO
i
OMe OMe
4
5a 53%
MeOH
5a–l
MeO
OMe
TMSOTf
4
TMSOMe
Scheme 3 Synthesis of 5a–l. Reagents and conditions: (i) 1. TMSOTf
(0.1 equiv), CH2Cl2, –78 to 20 °C, 20 h; 2. HCl, H2O.
SPh
O
OTf –
MeO
OMe
OMe
+
OMe
OMe
In conclusion, we have reported a convenient approach to
2-(arylthio)benzoates by the first catalytic [3+3] cycliza-
tions of 3-(arylthio)-1-(trimethylsilyloxy)-1,3-butadienes
with 1,1,3,3-tetramethoxypropane. The scope and appli-
cations of this methodology are currently studied in our
laboratory.
MeO
A
D
3a
TfOH
TMSOTf
O
O
PhS
OMe
PhS
OMe
Acknowledgment
TMSOTf
OTf –
OMe
OMe
OMe
Financial support by the State of Pakistan (scholarships for I. I., N. R.
and M. A. R.) and by the State of Mecklenburg-Vorpommern is gra-
tefully acknowledged.
+
MeO
MeO
TMSOMe
B
C
Scheme 2 Possible mechanism of the formation of 5a. Reagents
and conditions: (i) 1. TMSOTf (0.1 equiv), CH2Cl2, –78 to 20 °C,
20 h; 2. HCl, H2O.
References and Notes
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and the concentration (ca. 2 mL of CH2Cl2 per 1 mmol of
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clization of 1,3-bis(silyloxy)-1,3-butadienes with 4. The
Synlett 2008, No. 17, 2708–2710 © Thieme Stuttgart · New York

2710
M. Imran et al.
LETTER
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To a CH2Cl2 solution (2 mL/mmol of 3) of 3 (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
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Methyl 2-(Phenylthio)benzoate (5a)
Starting with 1,1,3,3-tetramethoxypropane (0.33 mL,
2.0 mmol), 3a (843 mg, 3.0 mmol), TMSOTf (0.036 mL,
0.2 mmol), and CH2Cl2 (4 mL), 5a was isolated as a highly
viscous colourless oil (275 mg, 53%). 1H NMR (250 MHz,
CDCl3): d = 3.66 (s, 3 H, OCH3), 6.75 (dd, 1 H, 3J = 7.20,
4J = 1.87 Hz, ArH), 7.06 (ddd, 1 H, 3J = 7.20, 4J = 1.87,
5J = 0.92 Hz, ArH), 7.16 (m, 2 H, ArH), 7.36 (m, 3 H, ArH),
7.48 (m, 2 H, ArH). 13C NMR (62 MHz, CDCl3): d = 52.1
(OCH3), 124.2 (ArCH), 126.7 (C), 127.4, 129.0 (ArCH),
129.7 (2C, ArCH), 131.1, 132.2 (ArCH), 124.6 (C), 135.5
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70 eV): m/z (%) = 244 (100), 213 (76), 184 (55), 152 (16),
139 (10), 108 (8). HRMS (EI): m/z calcd for C14H12O2S
[M+]: 244.05525; found: 244.05570.
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