Synthesis of 5-arylthio-3-hydroxyphthalates by the first [4+2] cycloadditions of 3-arylthio-1-silyloxy-1,3-butadienes with dimethyl acetylenedicarboxylate

Article abstract of DOI:10.1055/s-0029-1216828

A variety of 5-arylthio-3-hydroxyphthalates were prepared by [4+2] cycloadditions of 3-arylthio-1-trimethylsilyloxy-1,3-butadienes with dimethyl acetylenedicarboxylate. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-0029-1216828

2430
PAPER
Synthesis of 5-Arylthio-3-hydroxyphthalates by the First [4+2] Cycloadditions
of 3-Arylthio-1-silyloxy-1,3-butadienes with Dimethyl Acetylenedicarboxylate
S
ynthesi
n
s
of 5-Arylth
aio-3-hydro
m
a
Institut für Chemie, Universität Rostock, Albert Einstein Str. 3a, 18059 Rostock, Germany
E-mail: peter.langer@uni-rostock.de
b
Leibniz-Institut für Katalyse an der Universität Rostock e.V., Albert Einstein Str. 29a, 18059 Rostock, Germany
Received 2 January 2009; revised 26 March 2009
arylthio-1-trimethylsilyloxy-1,3-butadienes with 1,1-di-
acylcyclopropanes.14
Abstract: A variety of 5-arylthio-3-hydroxyphthalates were pre-
pared by [4+2] cycloadditions of 3-arylthio-1-trimethylsilyloxy-
1,3-butadienes with dimethyl acetylenedicarboxylate.
Herein, we report on the [4+2] cycloaddition reactions of
3-arylthio-1-trimethylsilyloxy-1,3-butadienes with dime-
thyl acetylenedicarboxylate (DMAD). This method pro-
vides a convenient and general approach to a wide range
of novel 5-arylthio-3-hydroxyphthalates which are not
readily available by other methods. In contrast to the C–S
coupling reactions outlined above, the method reported
herein relies on the assembly of one of the two arene moi-
eties.
Key words: arenes, cyclizations, diaryl sulfides, regioselectivity,
silyl enol ethers
Diaryl sulfides are of pharmacological importance and are
found in many natural products. Such compounds include,
for example, the lissoclibadins, dibenzothiophenes, cyclic
sulfides, varacins (lissoclinotoxins), and related natural
products.1 Diaryl sulfides are available by reaction of ar-
enes with sulfur2 or sulfur dichloride,3 by condensation of
organometallic reagents with chlorophenylsulfides4 or by
base-mediated reactions of thiophenols with chloroar-
enes.5 However, competing formation of polysulfides and
(in several cases) the low regioselectivities of the reac-
tions are severe drawbacks of these classic synthetic ap-
proaches. In recent years, a number of transition-metal
catalyzed6 and metal-free,7 carbon–sulfur coupling reac-
tions have been developed which allow the formation of
diaryl sulfides under mild conditions. However, 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
difficult and tedious task.
The known 3-arylthio-1-trimethylsilyloxy-1,3-butadienes
2a–j were prepared from either methyl acetoacetate or
methyl 3-oxopentanoate and from the corresponding
thiophenols in two steps.13,15,16
The [4+2] cycloaddition of DMAD (1) with 3-phenylthio-
1-trimethylsilyloxy-1,3-butadiene (2a) resulted in forma-
tion of the 5-phenylthio-3-hydroxyphthalate (3a) in up to
77% yield (Scheme 1). The best yields were obtained
when a 2a/1 ratio of ~1:2 was used, when the reaction was
carried out without solvent (neat), when the temperature
was allowed to slowly rise from –78 °C to 20 °C, and
when an aqueous solution of ammonium chloride was
used for the work-up (to induce the aromatization). An in-
separable 1:2 mixture of 3a and 5-phenylthio-3-methox-
yphthalate was reported to be obtained when a benzene
solution of the starting materials was stirred at –10 °C for
16 hours and when the reaction was quenched by addition
of tetrahydrofuran and hydrochloric acid (5%).13 The re-
action presumably proceeds by cycloaddition to give in-
termediate A (Scheme 1). Subsequently, cleavage of the
silyl ether under the acidic work-up conditions and elimi-
nation of methanol from the intermediary hemiacetal, af-
forded the product 3a.
An alternative approach to the synthesis of diaryl sulfides
is based on the use of sulfur-containing building blocks in
cyclization reactions. Hilt and co-workers reported a con-
venient approach to diaryl sulfides by cobalt(I)-catalyzed
[4+2] cycloaddition of alkynyl sulfides with 1,3-buta-
dienes.8 Recently, we have studied9 the synthesis of 3- and
5-(arylthio)salicylates by titanium tetrachloride-mediated
formal [3+3] cyclizations10 of 1,3-bis(silyloxy)-1,3-
butadienes11 with 3-silyloxy-2-en-1-ones.12 Chan et al. re-
ported the synthesis of 2-(phenylthio)benzoates by TiCl4-
mediated [3+3] cyclization of 3-silyloxy-2-en-1-ones
with 1-methoxy-3-phenylthio-1-trimethylsilyloxy-1,3-
butadiene.13 We have recently reported the synthesis of 5-
chloroethyl-2-(arylthio)benzoates by TiCl4-mediated
domino ‘[3+3] cyclization / homo-Michael’ reaction of 3-
The cyclization of DMAD with 3-arylthio-1-trimethylsi-
lyloxy-1,3-butadienes 2a–l afforded the novel 5-arylthio-
3-hydroxyphthalates 3a–l in moderate to good yields
(Scheme 2, Table 1). A wide range of products could be
successfully prepared. The best yields were obtained for
products derived from dienes containing an electron-rich
aryl group. The yield of product 3h, containing a bulky
naphthyl group, was lower than the yield of 3a, which
contains a phenyl group. The yields dropped slightly us-
ing dienes containing a C-4 methyl group.
SYNTHESIS 2009, No. 14, pp 2430–2434
x
x.
x
x
.
2
0
0
9
Advanced online publication: 27.05.2009
DOI: 10.1055/s-0029-1216828; Art ID: T00109SS
© Georg Thieme Verlag Stuttgart · New York

PAPER
Synthesis of 5-Arylthio-3-hydroxyphthalates
2431
All solvents were dried by standard methods and all reactions were
carried out under an inert atmosphere. For 1H and 13C NMR spectra,
the deuterated solvents indicated were used. Mass spectrometric
data (MS) were obtained by electron ionization (EI, 70 eV), chemi-
cal ionization (CI, H2O) or electrospray ionization (ESI). IR spectra
were recorded using the indicated techniques. For preparative scale
chromatography, silica gel (60–200 mesh) was used. Melting points
are uncorrected. Dienes 2a–l were prepared according to the litera-
ture.13,15,16
SPh
PhS
OSiMe3
OMe
i
2a
MeO2C
OH
CO2Me
+
MeO2C
CO2Me
3a (77%)
1
ii
SPh
General Procedure
To neat 2a–l (1.5 mmol), was added 1 (2.25 mmol) at –78 °C. The
solution was allowed to warm to 20 °C during 20 h with stirring. To
the solution was added aq NH4Cl (10%, 25 mL) and CH2Cl2 (20
mL). The organic and the aqueous layers were separated and the lat-
ter was extracted with CH2Cl2 (3 × 20 mL). The combined organic
layers were dried (Na2SO4), filtered, and the filtrate was concentrat-
ed in vacuo to give a residue which was purified by chromatography
(EtOAc–heptanes, 1:9).
OSiMe3
OMe
MeO2C
CO2Me
A
Scheme 1 Possible mechanism for the formation of arene 3a.
Reagents and conditions: (i) (a) neat, –78 to 20 °C, 20 h; (b) NH4Cl,
H2O; (ii) NH4Cl, H2O.
Dimethyl 3-Hydroxy-5-phenylsulfanylphthalate (3a)
Starting with 2a (420 mg, 1.5 mmol) and 1 (319 mg, 2.25 mmol),
3a was isolated.
ArS
OSiMe3
OMe
SAr
R
R
Yield: 367 mg (77%); highly viscous oil.
i
2a–l
IR (KBr): 3057 (w), 3000 (w), 2950 (w), 2845 (w), 1732 (s), 1668
(s), 1596 (s), 1556 (m), 1474 (m), 1437 (s), 1329 (s), 1265 (s), 1197
(s), 1167 (s), 1120 (s), 1068 (m), 1016 (s), 933 (m), 852 (m), 802
(m), 774 (m), 744 (s), 689 (s), 562 (m) cm–1.
MeO2C
OH
CO2Me
+
MeO2C
CO2Me
3a–l
1
1H NMR (250 MHz, CDCl3): d = 3.65 (s, 3 H, OCH3), 3.69 (s, 3 H,
OCH3), 6.48–7.32 (m, 7 Harom), 10.57 (s, 1 H, OH).
Scheme 2 Synthesis of arenes 3a–l. Reagents and conditions: (i) (a)
neat, –78 to 20 °C, 20 h; (b) NH4Cl, H2O.
13C NMR (63 MHz, CDCl3): d = 52.6 (OCH3), 52.8 (OCH3), 106.6
(C), 116.2, 117.1, 129.5 (CHarom), 129.9 (2 × CHAr), 130.0 (C),
134.8 (2 × CHarom), 135.7, 148.3, 161.7, 168.9, 169.0 (C).
Table 1 Synthesis of Arenes 3a–l
MS (EI, 70 eV): m/z (%) = 319 (18), 318 (100) [M+], 287 (34), 285
(55), 270 (11), 269 (65), 253 (16), 228 (20), 226 (10), 200 (27), 198
(11), 171 (25).
2,3
a
b
c
R
Ar
Yield of 3 (%)a
H
Ph
77
69
64
51
64
69
67
54
60
59
55
53
HRMS (EI): m/z [M+] calcd for C16H14O5S: 318.05565; found:
318.055736.
H
4-MeC6H4
4-ClC6H4
4-FC6H4
4-EtC6H4
4-EtC6H4
3-MeC6H4
2-Naphthyl
3-ClC6H4
4-MeC6H4
4-ClC6H4
4-FC6H4
H
Dimethyl 3-Hydroxy-5-(4-methylphenylsulfanyl)phthalate (3b)
Starting with 2b (441 mg, 1.5 mmol) and 1 (319 mg, 2.25 mmol),
3b was isolated.
d
e
H
Me
H
Yield: 344 mg (69%); highly viscous oil.
f
IR (KBr): 3022 (w), 2998 (w), 2950 (w), 2921 (w), 2847 (w), 1733
(s), 1668 (s), 1595 (s), 1555 (m), 1491 (m), 1433 (s), 1331 (s), 1266
(s), 1196 (s), 1164 (s), 1120 (s), 1016 (s), 934 (m), 852 (m), 802 (s),
773 (m), 744 (m), 703 (m), 636 (m), 586 (m), 567 (m) cm–1.
g
h
i
H
H
1H NMR (250 MHz, CDCl3): d = 2.32 (s, 3 H, CH3), 3.77 (s, 3 H,
OCH3), 3.80 (s, 3 H, OCH3), 6.54–6.60 (dd, J = 1.8 Hz, 2 Harom),
7.17 (d, J = 8.2 Hz, 2 Harom), 7.35 (d, J = 8.2 Hz, 2 Harom), 10.69 (s,
1 H, OH).
H
j
Me
Me
Me
k
l
13C NMR (63 MHz, CDCl3): d = 21.3 (CH3), 52.6 (OCH3), 52.7
(OCH3), 106.3 (C), 115.6, 116.7 (CHarom), 126.0, 130.6 (C), 130.7
(2 × CHarom), 135.1 (2 × CHarom), 140.0, 149.1, 161.5, 169.0, 169.1
(C).
a Yield of isolated products.
MS (EI, 70 eV): m/z (%) = 333 (17), 332 (100) [M+], 301 (22), 299
(34), 285 (15), 283 (47), 267 (12), 242 (11), 214 (15).
In conclusion, we have reported a convenient synthesis of
a variety of 5-arylthio-3-hydroxyphthalates by the first
[4+2] cycloadditions of 3-arylthio-1-trimethylsilyloxy-
1,3-butadienes with dimethyl acetylenedicarboxylate.
The scope and applications of this methodology are cur-
rently under study in our laboratory.
HRMS (EI): m/z [M+] calcd for C17H16O5S: 332.07130; found:
332.071408.
Dimethyl 3-Hydroxy-5-(4-chlorophenylsulfanyl)phthalate (3c)
Starting with 2c (471mg, 1.5 mmol) and 1 (319 mg, 2.25 mmol), 3c
was isolated.
Synthesis 2009, No. 14, 2430–2434 © Thieme Stuttgart · New York

2432
I. Iqbal et al.
PAPER
Dimethyl 3-Hydroxy-5-(4-ethylphenylsulfanyl)phthalate (3f)
Starting with 2f (462 mg, 1.5 mmol) and 1 (319 mg, 2.25 mmol), 3f
Yield: 338 mg (64%); highly viscous oil.
IR (KBr): 3079 (w), 3044 (w), 3006 (w), 2955 (w), 2853 (w), 1727
(s), 1673 (s), 1594 (s), 1557 (s), 1475 (m), 1440 (s), 1434 (s), 1406
(m), 1388 (m), 1328 (s), 1265 (s), 1199 (s), 1164 (s), 1120 (s), 1016
(s), 934 (m), 852 (m), 802 (s), 773 (m), 744 (m), 703 (m), 636 (m),
586 (m), 567 (m) cm–1.
was isolated.
Yield: 358 mg (69%); highly viscous oil.
IR (KBr): 3094 (w), 3067 (w), 2999 (w), 2951 (w), 2847 (w), 1732
(s), 1669 (s), 1588 (s), 1555 (m), 1488 (s), 1435 (m), 14397 (m),
1332 (s), 1268 (s), 1218 (s), 1198 (s), 1169 (s), 1155 (s), 1121(s),
1089 (m), 1014 (s), 934 (m), 832 (s), 802 (s), 702 (m), 638 (m), 566
(m) cm–1.
1H NMR (250 MHz, CDCl3): d = 3.70 (s, 3 H, OCH3), 3.74 (s, 3 H,
OCH3), 6.52–7.31 (m, 6 Harom), 10.62 (s, 1 H, OH).
13C NMR (63 MHz, CDCl3): d = 52.7 (OCH3), 52.8 (OCH3), 107.0
(C), 116.4, 117.2 (CHarom), 126.9, 128.7 (C), 130.1 (2 × CHarom),
135.9 (2 × CHarom), 147.3, 149.1, 161.5, 168.8, 168.9 (C).
1H NMR (300 MHz, CDCl3): d = 1.19 (t, J = 7.6 Hz, 3 H, CH3), 2.61
(q, J = 7.6 Hz, 2 H, CH2), 3.76 (s, 3 H, OCH3), 3.79 (s, 3 H, OCH3),
6.17–6.21 (dd, J = 8.2, 1.8 Hz, 2 Harom), 7.06 (d, J = 8.2 Hz,
2 Harom), 7.23 (d, J = 8.2 Hz, 2 Harom), 10.69 (s, 1 H, OH).
MS (EI, 70 eV): m/z (%) = 354 (35) [M+], 353 (16), 352 (100) [M+],
323 (12), 322 (12), 321 (48), 320 (20), 319 (42), 305 (19), 303 (44),
287 (13), 264 (13), 262 (36), 260 (12), 234 (24), 171 (11).
13C NMR (75 MHz, CDCl3): d = 15.2 (CH3), 28.6 (CH2), 52.6
(OCH3), 52.7 (OCH3), 106.4 (C), 115.7, 116.8 (CHarom), 126.3 (C),
129.5, 135.1 (2 × CHarom), 135.7, 146.2, 149.1, 161.5, 169.0, 169.1
(C).
HRMS (EI): m/z [M+] calcd for C16H13O5SCl: 352.01667; found:
352.016164.
Dimethyl 3-Hydroxy-5-(4-fluorophenylsulfanyl)phthalate (3d)
Starting with 2d (447 mg, 1.5 mmol) and 1 (319 mg, 2.25 mmol),
3d was isolated.
MS (EI, 70 eV): m/z (%) = 347 (21), 346 (100) [M+], 315 (24), 313
(35), 299 (12), 298 (11), 297 (53), 285 (33), 281 (14), 228 (10), 227
(10), 226 (10) cm–1.
Yield: 257 mg (51%); highly viscous oil.
HRMS (EI): m/z [M+] calcd for C18H18O5S: 346.08695; found:
346.086443.
IR (KBr): 3094 (w), 3067 (w), 2999 (w), 2951 (w), 2847 (w), 1732
(s), 1669 (s), 1588 (s), 1555 (m), 1488 (s), 1435 (m), 14397 (m),
1332 (s), 1268 (s), 1218 (s), 1198 (s), 1169 (s), 1155 (s), 1121 (s),
1089 (m), 1014 (s), 934 (m), 832 (s), 802 (s), 702 (m), 638 (m), 567
(m) cm–1.
Dimethyl 3-Hydroxy-5-(4-methylphenylsulfanyl)phthalate (3g)
Starting with 2g (441 mg, 1.5 mmol) and 1 (319 mg, 2.25 mmol),
3g was isolated.
Yield: 333 mg (67%); highly viscous oil.
1H NMR (250 MHz, CDCl3): d = 3.69 (s, 3 H, OCH3), 3.73 (s, 3 H,
OCH3), 6.45–7.33 (m, 6 Harom), 10.62 (s, 1 H, OH).
IR (KBr): 3022 (w), 2998 (w), 2950 (w), 2921 (w), 2847 (w), 1733
(s), 1668 (s), 1595 (s), 1555 (m), 1491 (m), 1433 (s), 1331 (s), 1266
(s), 1196 (s), 1164 (s), 1120 (s), 1016 (s), 934 (m), 852 (m), 802 (s),
773 (m), 744 (m), 703 (m), 636 (m), 586 (m), 567 (m) cm–1.
13C NMR (75 MHz, CDCl3): d = 52.7 (OCH3), 52.8 (OCH3), 106.0
(C), 115.8, 116.7, 117.0, 117.3 (CHarom), 135.8, (C), 137.2, 137.3
(CHarom), 148.3, 161.5, 161.9, 165.3, 168.9, 169.0 (C).
1H NMR (300 MHz, CDCl3): d = 2.28 (s, 3 H, CH3), 3.77 (s, 3 H,
OCH3), 3.80 (s, 3 H, OCH3), 6.58–7.24 (m, 6 Harom), 10.68 (s, 1 H,
OH).
MS (EI, 70 eV): m/z (%) = 337 (16), 336 (100) [M+], 305 (36), 304
(24), 303 (39), 287 (38), 271 (12), 246 (42), 244 (11), 218 (25), 216
(10), 189 (16).
13C NMR (63 MHz, CDCl3): d = 21.2 (CH3), 52.6 (OCH3), 52.7
(OCH3), 106.5 (C), 116.1, 117.0 (CHarom), 129.5 (C), 129.7, 130.4,
131.9, 135.4 (CHarom), 135.7, 139.8, 148.6, 161.5, 169.0, 169 (C).
HRMS (EI): m/z [M+] calcd for C16H13O5SF: 336.04622; found:
336.045809.
Dimethyl 3-Hydroxy-6-(4-ethylphenylsulfanyl)-4-methylphtha-
late (3e)
MS (EI, 70 eV): m/z (%) = 333 (17), 332 (100) [M+], 301 (22), 299
(34), 285 (15), 283 (47), 267 (12), 242 (11), 214 (15).
Starting with 2e (483 mg, 1.5 mmol) and 1 (319 mg, 2.25 mmol), 3e
was isolated.
HRMS (EI): m/z [M+] calcd for C17H16O5S: 332.07130; found:
332.071173.
Yield: 345 mg (64%); highly viscous oil.
Dimethyl 3-Hydroxy-5-(2-naphthyl)sulfanylphthalate (3h)
Starting with 2h (496 mg, 1.5 mmol) and 1 (319 mg, 2.25 mmol),
3h was isolated.
IR (KBr): 3071 (w), 3021 (w), 2951 (w), 2873 (w), 1735 (s), 1667
(s), 1590 (s), 1562 (s), 1492 (m), 1430 (s), 1331 (s), 1278 (m), 1217
(s), 1125 (s), 1042 (s), 1004 (m), 939 (s), 827 (s), 802 (s), 743 (s)
cm–1.
Yield: 298 mg (54%); highly viscous oil.
1H NMR (300 MHz, CDCl3): d = 1.09 (t, J = 7.6 Hz, 3 H, CH3), 2.03
(s, 3 H, CH3), 2.51 (q, J = 7.6 Hz, 2 H, CH2), 3.70 (s, 3 H, OCH3),
3.73 (s, 3 H, OCH3), 6.19 (s, 1 Harom), 7.08 (d, J = 8.2 Hz, 2 Harom),
7.23 (d, J = 8.2 Hz, 2 Harom), 10.68 (s, 1 H, OH).
IR (KBr): 3052 (w), 2999 (w), 2949 (w), 2840 (w), 1731 (s), 1666
(s), 1595 (s), 1555 (s), 1497 (m), 1434 (s), 1400 (m), 1330 (s), 1264
(s), 1196 (s), 1167 (s), 1119 (s), 1016 (s), 934 (s), 850 (s), 802 (s),
742 (s), 646 (m) cm–1.
13C NMR (63 MHz, CDCl3): d = 15.2 (CH2CH3), 15.8 (CH3), 28.6
(CH2), 52.4 (OCH3), 52.8 (OCH3), 105.0 (C), 114.8 (CHarom), 122.3,
126.2 (C), 129.6 (2 × CHarom), 134.7 (C), 135.5 (2 × CHarom), 146.3,
150.2, 159.8, 169.2, 169.4 (C).
1H NMR (250 MHz, CDCl3): d = 3.68 (s, 3 H, OCH3), 3.72 (s, 3 H,
OCH3), 6.56–7.92 (m, 8 Harom), 10.60 (s, 1 H, OH).
13C NMR (63 MHz, CDCl3): d = 52.6 (OCH3), 52.8 (OCH3), 106.6
(C), 116.4, 117.2 (CHAr), 127.2 (C), 127.3, 127.8, 127.9, 129.7,
130.9 (CHarom), 133.3, 133.8 (C), 134.7, 134.9 (CHarom), 135.8,
148.1, 161.5, 168.9, 169.0 (C).
MS (EI, 70 eV): m/z (%) = 361 (22), 360 (100) [M+], 329 (27), 326
(26), 313 (17), 312 (12), 311 (56), 299 (29), 296 (39), 270 (10), 268
(10), 267 (26), 240 (12).
MS (EI, 70 eV): m/z (%) = 369 (19), 368 (100) [M+], 337 (11), 335
(17), 319 (24), 303 (18), 250 (19), 248 (10), 221 (12).
HRMS (EI): m/z [M+] calcd for C19H20O5S: 360.10260; found:
360.101772.
HRMS (EI): m/z [M+] calcd for C20H16O5S: 368.07130; found:
368.071809.
Synthesis 2009, No. 14, 2430–2434 © Thieme Stuttgart · New York

PAPER
Synthesis of 5-Arylthio-3-hydroxyphthalates
2433
Dimethyl 3-Hydroxy-5-(3-chlorophenylsulfanyl)phthalate (3i)
Starting with 2i (471 mg, 1.5 mmol) and 1 (319 mg, 2.25 mmol), 3i
was isolated.
HRMS (EI): m/z [M+] calcd for C17H15O5SCl: 366.03232; found:
366.031813.
Dimethyl 3-Hydroxy-6-(4-fluorophenylsulfanyl)-4-methyl-
phthalate (3l)
Starting with 2l (468 mg, 1.5 mmol) and 1 (319 mg, 2.25 mmol), 3l
was isolated.
Yield: 317 mg (60%); highly viscous oil.
IR (KBr): 3079 (w), 3044 (w), 3006 (w), 2955 (w), 2853 (w), 1727
(s), 1673 (s), 1594 (s), 1557 (s), 1475 (m), 1440 (s), 1434 (s), 1406
(m), 1388 (m), 1328 (s), 1265 (s), 1199 (s), 1164 (s), 1120 (s), 1016
(s), 934 (m), 852 (m), 802 (s), 773 (m), 744 (m), 703 (m), 636 (m),
586 (m), 567 (m) cm–1.
Yield: 378 mg (53%); highly viscous oil.
IR (KBr): 3075 (w), 3025 (w), 2951 (w), 2871 (w), 1736 (s), 1667
(s), 1591 (s), 1562 (s), 1492 (m), 1432 (s), 1331 (s), 1278 (m), 1217
(s), 1128 (s), 1046 (s), 1004 (m), 945 (s), 827 (s), 802 (s), 747 (s)
cm–1.
1H NMR (250 MHz, CDCl3): d = 3.78 (s, 3 H, OCH3), 3.82 (s, 3 H,
OCH3), 6.64–7.30 (m, 6 Harom), 10.69 (s, 1 H, OH).
13C NMR (63 MHz, CDCl3): d = 52.7 (OCH3), 52.8 (OCH3), 107.0
(C), 117.1, 117.8, 129.5, 130.8, 132.3 (CHarom), 132.5 (C), 133.9
(CHarom), 135.4, 136.0, 146.5, 161.5, 168.7, 168.9 (C).
1H NMR (300 MHz, CDCl3): d = 2.06 (s, 3 H, CH3), 3.73 (s, 3 H,
OCH3), 3.76 (s, 3 H, OCH3), 6.16–7.33 (m, 5 Harom), 10.71 (s, 1 H,
OH).
MS (EI, 70 eV): m/z (%) = 354 (35) [M+], 353 (16), 352 (100) [M+],
323 (12), 322 (12), 321 (48), 320 (20), 319 (42), 305 (19), 303 (44),
287 (13), 264 (13), 262 (36), 260 (12), 234 (24), 171 (11).
13C NMR (63 MHz, CDCl3): d = 15.7 (CH3), 52.4 (OCH3), 52.8
(OCH3), 105.9 (C), 115.0, 117.1, 117.5 (CHarom), 122.4, 125.1 (C),
137.4, 137.6 (CHarom), 137.8, 137.9, 149.3, 159.8, 169.0, 169.2 (C).
HRMS (EI): m/z [M+] calcd for C16H13O5SCl: 352.01667; found:
352.016166.
MS (EI, 70 eV): m/z (%) = 351 (19), 350 (100) [M+], 327 (17), 326
(26), 313 (17), 312 (12), 311 (56), 299 (29), 296 (39), 270 (10), 268
(10), 267 (26), 240 (13).
Dimethyl 3-Hydroxy-6-(4-methylphenylsulfanyl)-4-methyl-
phthalate (3j)
Starting with 2j (462 mg, 1.5 mmol) and 1 (319 mg, 2.25 mmol), 3j
was isolated.
HRMS (EI): m/z [M+] calcd for C17H15O5SF: 350.04622; found:
350.04731.
Yield: 306 mg (59%); highly viscous oil.
Acknowledgment
IR (KBr): 3071 (w), 3021 (w), 2951 (w), 2873 (w), 1735 (s), 1667
(s), 1590 (s), 1562 (s), 1492 (m), 1430 (s), 1331 (s), 1278 (m), 1217
(s), 1125 (s), 1042 (s), 1004 (m), 939 (s), 827 (s), 802 (s), 743 (s)
cm–1.
Financial support by the State of Pakistan (HEC scholarship for
I. I.) and by the State of Mecklenburg-Vorpommern (scholarship
for M. I.) is gratefully acknowledged.
1H NMR (250 MHz, CDCl3): d = 2.14 (s, 3 H, CH3), 2.33 (s, 3 H,
CH3), 3.81 (s, 3 H, OCH3), 3.84 (s, 3 H, OCH3), 6.27 (s, 1 Harom),
7.18 (d, J = 8.2 Hz, 2 Harom), 7.36 (d, J = 8.2 Hz, 2 Harom), 10.78 (s,
1 H, OH).
References
(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.;
Barrows, L. R.; Ireland, C. M. J. Am. Chem. Soc. 1991, 113,
4709. (d) Mori, Y.; Taneda, S.; Hayashi, H.; Sakushima, A.;
Kamata, K.; Suzuki, A. K.; Yoshino, S.; 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. 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, M. Tetrahedron 2005, 61, 8611. (g) Kaplan,
M. L.; Reents, W. D. Tetrahedron Lett. 1982, 23, 373.
(h) Hosoya, Y.; Adachi, H.; Nakamura, H.; Nishimura, Y.;
Naganawa, H. Tetrahedron Lett. 1996, 37, 9227.
13C NMR (63 MHz, CDCl3): d = 14.8 (CH3), 20.3 (CH3), 51.4
(OCH3), 51.8 (OCH3), 104.6 (C), 113.9 (CHarom), 121.3, 125.1 (C),
129.6, 129.8, 134.4, 134.5 (CHarom), 139.1, 149.2, 158.8, 168.1,
168.3 (C).
MS (EI, 70 eV): m/z (%) = 347 (22), 346 (100) [M+], 329 (27), 326
(26), 313 (17), 312 (12), 311 (56), 299 (29), 296 (39), 270 (10), 268
(10), 267 (26), 240 (12).
HRMS (EI): m/z [M+] calcd for C18H18O5S: 346.08695; found:
346.086893.
Dimethyl 3-Hydroxy-6-(4-chlorophenylsulfanyl)-4-methyl-
phthalate (3k)
Starting with 2k (492 mg, 1.5 mmol) and 1 (319 mg, 2.25 mmol),
3k was isolated.
(2) See for example: (a) Glass, H. B.; Reid, E. E. J. Am. Chem.
Soc. 1929, 51, 3428. (b) Dougherty, G.; Hammond, P. D.
J. Am. Chem. Soc. 1935, 57, 117. (c) For the
Yield: 302 mg (55%); highly viscous oil.
trifluoromethanesulfonic acid-catalyzed sulfurization of
cycloalkanes, see: Olah, G. A.; Wang, Q.; Prakash, G. K. S.
J. Am. Chem. Soc. 1990, 112, 3697.
IR (KBr): 3073 (w), 3025 (w), 2951 (w), 2873 (w), 1735 (s), 1667
(s), 1590 (s), 1562 (s), 1492 (m), 1430 (s), 1331 (s), 1278 (m), 1217
(s), 1128 (s), 1046 (s), 1004 (m), 945 (s), 827 (s), 802 (s), 747 (s)
cm–1.
(3) Kemp, D. S.; Carey, R. I.; Dewan, J. C.; Galakatos, N. G.;
Kerkman, D.; Leung, S.-L. J. Org. Chem. 1989, 54, 1589;
and references cited therein.
(4) Chua, M.; Hoyer, H. Z. Naturforsch., B 1965, 20, 416.
(5) (a) Baxter, I.; Ben-Haida, A.; Colquhoun, H. M.; Hodge, P.;
Kohnke, F. H.; Williams, D. J. Chem. Eur. J. 2000, 6, 4285;
and references cited therein. (b) Campbell, J. R. J. Org.
Chem. 1964, 29, 1830.
1H NMR (300 MHz, CDCl3): d = 2.16 (s, 3 H, CH3), 3.85 (s, 3 H,
OCH3), 3.87 (s, 3 H, OCH3), 6.36–7.42 (m, 5 Harom), 10.81 (s, 1 H,
OH).
13C NMR (63 MHz, CDCl3): d = 17.2 (CH3), 53.8 (OCH3), 54.0
(OCH3), 106.6 (C), 117.0 (CHarom), 124.1, 130.3, 130.5, 131.2 (C),
131.4, 137.3 (2 × CHarom), 149.5, 161.0, 170.2, 170.4 (C).
MS (EI, 70 eV): m/z (%) = 368 (39) [M+], 367 (19), 366 (100) [M+],
328 (17), 326 (26), 313 (17), 312 (12), 311 (56), 299 (29), 296 (39),
270 (10), 268 (10), 267 (26), 240 (13).
Synthesis 2009, No. 14, 2430–2434 © Thieme Stuttgart · New York

2434
I. Iqbal et al.
PAPER
(6) (a) Taniguchi, N. J. Org. Chem. 2007, 72, 1241.
(b) Fernández-Rodríguez, M. A.; Shen, Q.; Hartwig, J. F.
J. Am. Chem. Soc. 2006, 128, 2180. (c) Murata, M.;
Buchwald, S. L. Tetrahedron 2004, 60, 7397.
(7) (a) Gendre, F.; Yang, M.; Diaz, P. Org. Lett. 2005, 7, 2719.
(b) Bates, C. G.; Gujadhur, R. K.; Venkataraman, D. Org.
Lett. 2002, 4, 2803. (c) Rábai, J. Synthesis 1989, 523.
(8) (a) Hilt, G.; Lüers, S. Synthesis 2003, 1784. (b) Hilt, G.;
Lüers, S.; Harms, K. J. Org. Chem. 2004, 69, 624.
(9) (a) Rashid, M. A.; Reinke, H.; Langer, P. Tetrahedron Lett.
2007, 48, 2321. (b) Rashid, M. A.; Rasool, N.; Adeel, M.;
Reinke, H.; Fischer, C.; Langer, P. Tetrahedron 2008, 64,
3782.
(12) (a) Chan, T.-H.; Brownbridge, P. J. Am. Chem. Soc. 1980,
102, 3534. (b) Brownbridge, P.; Chan, T.-H.; Brook, M. A.;
Kang, G. J. Can. J. Chem. 1983, 61, 688.
(13) (a) Chan, T. H.; Prasad, C. V. C. J. Org. Chem. 1986, 51,
3012. (b) Chan, T. H.; Prasad, C. V. C. J. Org. Chem. 1987,
52, 110.
(14) Rashid, M. A.; Rasool, N.; Iqbal, I.; Imran, M.; Langer, P.
Tetrahedron Lett. 2008, 49, 2466.
(15) (a) Wilson, B. D. Synthesis 1992, 283. (b) Heilbron, I.;
Jones, E. R. H.; Julia, M. J. Chem. Soc. 1949, 1434.
(c) Searles, S.; Sanchez, R. A.; Soulen, R. L.; Kundinger,
D. G. J. Org. Chem. 1967, 32, 2655. (d) Banville, J.;
Brassard, P. J. Chem. Soc., Perkin Trans. 1 1976, 1852.
(e) Barker, D.; Brimble, M. A.; Do, P.; Turner, P.
Tetrahedron 2003, 59, 2441.
(10) For a review of [3+3] cyclizations, see: Feist, H.; Langer, P.
Synthesis 2007, 327.
(11) For a review of 1,3-bis(silyloxy)-1,3-butadienes, see:
Langer, P. Synthesis 2002, 441.
(16) Iqbal, I.; Imran, M.; Villinger, A.; Langer, P. Synthesis 2009,
297.
Synthesis 2009, No. 14, 2430–2434 © Thieme Stuttgart · New York