Regioselective synthesis of 4-(arylsulfanyl)-2-hydroxyhomophthalates by [4+2] cycloaddition of 3-(arylsulfanyl)-1-(trimethylsilyloxy)buta-1,3-dienes with dimethyl penta-2,3-dienedioate

Article abstract of DOI:10.1002/hlca.200900348

The [4+2] cycloaddition of 3-(arylsulfanyl)-1-(trimethylsilyloxy)buta-1,3- dienes with dimethyl penta-2,3-dienedioate provides a convenient and regioselective approach to a variety of 4-(arylsulfanyl)-2- hydroxyhomophthalates.

Full text of DOI:10.1002/hlca.200900348

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Helvetica Chimica Acta – Vol. 93 (2010)
Regioselective Synthesis of 4-(Arylsulfanyl)-2-hydroxyhomophthalates by
[4 þ 2] Cycloaddition of 3-(Arylsulfanyl)-1-(trimethylsilyloxy)buta-1,3-dienes
with Dimethyl Penta-2,3-dienedioate
by Muhammad Imrana), Inam Iqbala), Christine Fischerb), and Peter Langer*a)b)
a) Institut fꢀr Chemie, Universitꢁt Rostock, Albert-Einstein-Str. 3a, D-18059 Rostock
(fax: þ 493814986412; e-mail: peter.langer@uni-rostock.de)
b) Leibniz-Institut fꢀr Katalyse e. V. an der Universitꢁt Rostock, Albert-Einstein-Str. 29a,
D-18059 Rostock
The [4 þ 2] cycloaddition of 3-(arylsulfanyl)-1-(trimethylsilyloxy)buta-1,3-dienes with dimethyl
penta-2,3-dienedioate provides a convenient and regioselective approach to a variety of 4-(arylsulfanyl)-
2-hydroxyhomophthalates.
1. Introduction. – Allenes are useful building blocks in inter- and intramolecular
[4 þ 2] cycloadditions [1]. Examples include the synthesis of functionalized phenols by
the [4 þ 2] cycloaddition of 2-(silyloxy) 1,3-dienes with allenes. For example, the
cycloaddition of a cyclic allenylester with 1,1-dimethoxy-3-(trimethylsilyloxy)-1,3-
butadiene is a key step during the synthesis of (R)-(þ)-lasiodiplodin [2]. 3-Methyl-4-
(phenylsulfonyl)phenol was prepared by the reaction of allenylphenylsulfone with
Danishefskyꢂs diene [3]. 4-Hydroxy- and 2,4-dihydroxyhomophthalates are available
by [4 þ 2] cycloaddition of 1,3-bis(trimethylsilyloxy)buta-1,3-dienes with dimethyl
penta-2,3-dienedioate [4][5]. This methodology was successfully applied to the
synthesis of an analogue of lactonamycin [6], of the N7-C25 fragment of psymberin
[7], and of the 4-acetylisocoumarins AGI-7 and sescandelin [8]. Herein, we report what
are, to the best of our knowledge, the first [4 þ 2] cycloadditions of 3-(arylsulfanyl)-1-
(trimethylsilyloxy)buta-1,3-dienes with dimethyl penta-2,3-dienedioate. These reac-
tions provide a convenient and regioselective approach to a variety of 4-(arylsulfanyl)-
2-hydroxyhomophthalates which can be regarded as highly functionalized diaryl
sulfides.
Diaryl sulfides are of considerable pharmacological relevance and occur in several
natural products. Examples include the lissoclibadins, dibenzothiophenes, cyclic
sulfides, varacins (lissoclinotoxins), and related natural products [9]. Diaryl sulfides
are available by reaction of arenes with sulfur1) or sulfur dichloride [11], by
condensation of organometallic reagents with chlorophenylsulfides [12] or by base-
mediated reactions of thiophenols with chloroarenes [13]. However, the competing
formation of polysulfides and, in several cases, the low regioselectivities are severe
1
)
For examples, see [10a] and [10b]. For the trifluoromethanesulfonic acid-catalyzed sulfurization of
cycloalkanes, see [10c].
ꢃ 2010 Verlag Helvetica Chimica Acta AG, Zꢀrich

Helvetica Chimica Acta – Vol. 93 (2010)
705
drawbacks of these classic synthetic approaches. In recent years, a number of transition
metal-catalyzed [14] and metal-free [15] C,S coupling reactions 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. An alternative approach to diaryl sulfides is based on the use
of sulfur-containing building blocks in cyclization reactions. Hilt and co-workers
reported a convenient approach to diaryl sulfides by a CoI-catalyzed [4 þ 2] cyclo-
addition of alkynyl sulfides with buta-1,3-dienes [16]. Recently, we have studied [17]
the synthesis of 3- and 5-(arylsulfanyl)salicylates by TiCl4-mediated formal [3 þ 3]
cyclizations2) of 1,3-bis(silyloxy)-1,3-butadienes3) with 3-(silyloxy) 2-en-1-ones [20].
Chan et al. [21] and our group [22] reported the synthesis of diaryl sulfides based on
cyclization reactions of 3-(arylsulfanyl)-1-(trimethylsilyloxy)buta-1,3-dienes. Herein,
we report, for the first time, the synthesis of 4-(arylsulfanyl)-2-hydroxyhomophthalates
by the [4 þ 2] cycloaddition of 3-(arylsulfanyl)-1-(trimethylsilyloxy)buta-1,3-dienes
with dimethyl penta-2,3-dienedioate.
2. Results and Discussion. – The known 3-(arylsulfanyl)-1-(trimethylsilyloxy)buta-
1,3-dienes 2a – 2l were prepared from methyl acetoacetate or methyl 3-oxopentanoate
and from the corresponding thiophenols in two steps [22][23]. Dimethyl penta-2,3-
dienedioate (1) was prepared by a known procedure [24]. The [4 þ 2] cycloaddition of 1
with 3-(phenylsulfanyl)-1-(trimethylsilyloxy)buta-1,3-diene 2a afforded 4-(phenylsul-
fanyl)-2-hydroxyhomophthalate (3a) in 85% yield (Scheme).
Scheme. Synthesis and Possible Mechanism of the Formation of the 4-(Arylsulfanyl)-2-hydroxyhomo-
phthalates 3a – 3l
The best yield was obtained when a stoichiometric ratio of 2a/1 1:1 was used and
when the reaction was carried out without solvent (neat). The yield decreased when the
reaction was carried out in a toluene solution (at room temperature or at elevated
2
)
)
For a review of [3 þ 3] cyclizations, see [18].
3
For a review of 1,3-bis(silyloxy)buta-1,3-dienes, see [19].

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Helvetica Chimica Acta – Vol. 93 (2010)
temperature). The starting materials were added at 08 and the mixture was
subsequently stirred at 50 – 708 for 12 h. The conversion was not complete when the
reaction was carried out at 208 or when the reaction time was decreased. In contrast, a
further increase of the temperature (higher than 708) resulted in decomposition. After
stirring for 12 h, an EtOH solution of triethylammonium fluoride (for complete
cleavage of the OꢀSi bond) [25] was added to the solution and, susequently, an
aqueous workup was carried out. The reaction presumably proceeds by cycloaddition
to give intermediate A. Subsequently, cleavage of the silyl ether and elimination of
MeOH from the intermediary hemiacetal afforded product 3a (Scheme). It is worth
noting that the selective elimination of MeOH (formation of a 2-hydroxyhomo-
phthalate) rather than H2O (formation of a 2-methoxyhomophthalate) was observed.
The cycloaddition of 1 with 3-(arylsulfanyl)-1-(trimethylsilyloxy)buta-1,3-dienes
2a – 2l afforded the novel 4-(arylsulfanyl)-2-hydroxyhomophthalates 3a – 3l in 50 – 85%
yield (Scheme and Table). 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 yields slightly dropped for dienes containing a Me group located at
C-atom C(4) of the diene, due to steric hindrance. The employment of allenes other
than 1 proved to be unsuccessful in our hands.
Table. Synthesis of the 4-(Arylsulfanyl)-2-hydroxyhomophthalates 3a – 3l
Compounds 2 and 3
R
Ar
Yield of 3 [%]a)
a
b
c
d
e
f
g
h
i
H
H
H
H
H
H
Me
Me
H
Ph
85
55
83
60
83
80
59
50
65
80
72
55
4-FꢀC6H4
3-MeꢀC6H4
3-ClꢀC6H4
4-MeꢀC6H4
Naphthalen-2-yl
Ph
4-FꢀC6H4
4-ClꢀC6H4
4-EtꢀC6H4
4-EtꢀC6H4
4-ClꢀC6H4
j
k
l
H
Me
Me
a) Yields of isolated products.
3. Conclusions. – We have reported a convenient and regioselective synthesis of 4-
(arylsulfanyl)-2-hydroxyhomophthalates by [4 þ 2] cycloadditions of 3-(arylsulfanyl)-
1-(trimethylsilyloxy)buta-1,3-dienes with dimethyl penta-2,3-dienedioate. Due to their
polyfunctionalized nature, 4-(arylsulfanyl)-2-hydroxyhomophthalates represent versa-
tile synthetic building blocks.
Experimental Part
General. Column chromatography: silica gel (SiO2; Merck). IR Spectra: Nicolet 380 FT-IR
spectrometer; in cmꢀ1. NMR Spectra: Bruker AVANCE 300 III and Bruker AVANCE 250 II
spectrometer; Me4Si as internal standard; d in ppm, J in Hz. EI-MS and HR-EI-MS: MAT 95-XP
instrument; in m/z.

Helvetica Chimica Acta – Vol. 93 (2010)
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General Experimental Procedure for the Synthesis of 3a – 3l. To neat 2a – 2l (1.5 mmol) was added 1
(1.5 mmol) at 08 and the mixture was stirred for 30 min. Subsequently, the mixture was stirred at 50 – 708
for 12 h. The soln. was allowed to cool to 208, and an EtOH soln. (2 ml, 96%) of Et3N · HF (1.5 mmol) was
added. The mixture was stirred for 10 min, and subsequently H2O and CH2Cl2 were added. The org. and
the aq. layer were separated, and the latter was extracted with CH2Cl2 (3 ꢁ 20 ml). The combined org.
layers were dried (Na2SO4), filtered, and the filtrate was concentrated in vacuo, and the residue was
purified by chromatography (SiO2; AcOEt/heptanes 1:9).
The known 3-(arylsulfanyl)-1-(trimethylsilyloxy)buta-1,3-dienes 2a – 2l were prepared from methyl
acetoacetate or methyl 3-oxopentanoate and from the corresponding thiophenols in two steps [22][23].
Dimethyl penta-2,3-dienedioate (1) was prepared by a known procedure [24].
Methyl 2-Hydroxy-6-(2-methoxy-2-oxoethyl)-4-(phenylsulfanyl)benzoate (3a). Starting with 2a
(420 mg, 1.5 mmol) and 1 (234 mg, 1.5 mmol), 3a was isolated as a highly viscous colorless oil (423 mg,
85%). IR (neat): 3056w, 2996w, 2950w, 2846w, 1736s, 1659s, 1599s, 1552m, 1474m, 1436s, 1320s, 1256s,
1
1194s, 1163s, 1122s, 1088m, 1067m, 1022m, 998m, 952m, 895s, 843m, 745m, 705s, 689s, 562m. H-NMR
(250 MHz, CDCl3): 3.60 (s, MeO); 3.71 (s, CH2); 3.78 (s, MeO); 6.43 (s, 1 arom. H); 6.49 (s, 1 arom. H);
7.32 – 7.44 (m, 5 arom. H); 11.26 (s, OH). 13C-NMR (63 MHz, CDCl3): 38.3 (CH2); 51.9 (MeO); 52.0
(MeO); 109.0 (arom. C); 114.5, 122.0, 129.0 (arom. CH each); 129.9 (2 arom. CH); 130.1 (arom. C);
134.8 (2 arom. CH); 136.6, 147.3, 163.3 (arom. C each); 170.8, 171.6 (2 CO). EI-MS (70 eV): 333 (20), 332
(100, Mþ), 273 (23), 272 (56), 258 (13), 257 (62), 240 (22), 213 (11), 184 (27), 51 (8). HR-EI-MS:
332.0711 (Mþ, C17H16O5Sþ; calc. 332.0712).
Methyl 4-[(4-Fluorophenyl)sulfanyl]-2-hydroxy-6-(2-methoxy-2-oxoethyl)benzoate (3b). Starting
with 2b (447 mg, 1.5 mmol) and 1 (234 mg, 1.5 mmol), 3b was isolated as a highly viscous colorless oil
(288 mg, 55%). IR (neat): 3055w, 2996w, 2950w, 2846w, 1736s, 1659s, 1599s, 1552m, 1474m, 1436s, 1320s,
1256s, 1194s, 1163s, 1122s, 1088m, 1067m, 1022m, 998m, 952m, 895s, 843m, 745m, 705s, 689s, 562m.
1H-NMR (250 MHz, CDCl3): 3.47 (s, MeO); 3.63 (s, MeO); 3.69 (s, CH2); 6.41(s, 1 arom. H); 6.49 (s, 1
arom. H); 7.11 – 7.34 (m, 4 arom. H); 11.26 (s, OH). 13C-NMR (63 MHz, CDCl3): 38.3 (CH2); 52.9
(MeO); 53.2 (MeO); 109.0 (arom. C); 114.5, 129.0 (arom. CH each); 129.9 (2 arom. CH); 130.1 (arom.
C); 134.8 (2 arom. CH); 136.6, 137.5, 147.3, 163.3 (arom. C each); 170.8, 171.6 (2 CO). EI-MS (70 eV):
351 (18), 350 (100, Mþ), 319 (13), 318 (19), 273 (23), 272 (56), 258 (13), 257 (62), 240 (22), 213 (11), 184
(27), 51 (8). HR-EI-MS: 350.0616 (Mþ, C17H15FO5Sþ; calc. 350.0619).
Methyl 2-Hydroxy-6-(2-methoxy-2-oxoethyl)-4-[(3-methylphenyl)sulfanyl]benzoate (3c). Starting
with 2c (441 mg, 1.5 mmol) and 1 (234 mg, 1.5 mmol), 3c was isolated as a highly viscous colorless oil
(430 mg, 83%). IR (neat): 3056w, 2996w, 2950w, 2846w, 1736s, 1659s, 1599s, 1552m, 1474m, 1436s, 1321s,
1256s, 1194s, 1163s, 1123s, 1088m, 1067m, 1022m, 998m, 952m, 895s, 843m, 745m, 705s, 689s, 562m.
1H-NMR (250 MHz, CDCl3): 2.31 (s, Me); 3.60 (s, MeO); 3.72 (s, CH2); 3.78 (s, MeO); 6.43 (s, 1 arom.
H); 6.49 (s, 1 arom. H); 7.32 – 7.44 (m, 4 arom. H); 11.26 (s, OH). 13C-NMR (63 MHz, CDCl3): 21.3 (Me);
42.5 (CH2); 51.9 (MeO); 52.2 (MeO); 109.0 (arom. C); 113.9, 121.5 (arom. CH each); 130.1 (arom. C);
130.6 (2 arom. CH); 131.1 (2 arom. CH); 135.4, 136.6, 147.3, 163.3 (arom. C each); 170.8, 171.6 (2 CO).
EI-MS (70 eV): 347 (20), 346 (100, Mþ), 273 (23), 272 (56), 258 (13), 257 (62), 240 (22), 213 (11), 184
(27), 51 (8). HR-EI-MS: 346.0879 (Mþ, C18H18O5Sþ; calc. 346.0870).
Methyl 4-[(3-Chlorophenyl)sulfanyl]-2-hydroxy-6-(2-methoxy-2-oxoethyl)benzoate (3d). Starting
with 2d (471 mg, 1.5 mmol) and 1 (234 mg, 1.5 mmol), 3d was isolated as a highly viscous colorless oil
(329 mg, 60%). IR (neat): 3055w, 2996w, 2950w, 2846w, 1736s, 1659s, 1599s, 1552m, 1474m, 1436s, 1320s,
1256s, 1194s, 1163s, 1122s, 1088m, 1067m, 1022m, 998m, 952m, 895s, 843m, 745m, 705s, 689s, 562m.
1H-NMR (250 MHz, CDCl3): 3.46 (s, MeO); 3.58 (s, MeO); 3.68 (s, CH2); 6.42 (s, 1 arom. H); 6.48 (s, 1
arom. H); 7.11 – 7.34 (m, 4 arom. H); 11.26 (s, OH). 13C-NMR (63 MHz, CDCl3): 38.3 (CH2); 52.9
(MeO); 53.2 (MeO); 109.0 (arom. C); 114.5, 129.0 (arom. CH each); 129.9 (2 arom. CH); 130.1 (arom.
C); 134.8 (2 arom. CH); 136.6, 137.5, 147.3, 163.3 (arom. C each); 170.8, 171.6 (2 CO). EI-MS (70 eV):
368 (37), 367 (18), 366 (100, Mþ), 335 (5), 273 (23), 272 (56), 258 (13), 257 (62), 240 (22), 213 (11), 184
(27), 51 (8). HR-EI-MS: 366.0322 (Mþ, C17H15ClO5Sþ; calc. 366.0323).
Methyl 2-Hydroxy-6-(2-methoxy-2-oxoethyl)-4-[(4-methylphenyl)sulfanyl]benzoate (3e). Starting
with 2e (441 mg, 1.5 mmol) and 1 (234 mg, 1.5 mmol), 3e was isolated as a highly viscous colorless oil
(430 mg, 83%). IR (neat): 3056w, 2996w, 2950w, 2846w, 1736s, 1659s, 1599s, 1552m, 1474m, 1436s, 1321s,

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Helvetica Chimica Acta – Vol. 93 (2010)
1256s, 1194s, 1163s, 1123s, 1088m, 1067m, 1022m, 998m, 952m, 895s, 843m, 745m, 705s, 689s, 562m.
1H-NMR (250 MHz, CDCl3): 2.32 (s, Me); 3.60 (s, MeO); 3.72 (s, CH2); 3.78 (s, MeO); 6.43 (s, 1 arom.
H); 6.49 (s, 1 arom. H); 7.32 – 7.44 (m, 4 arom. H); 11.26 (s, OH). 13C-NMR (63 MHz, CDCl3): 21.3 (Me);
42.5 (CH2); 51.9 (MeO); 52.2 (MeO); 109.0 (arom. C); 113.9, 121.5 (arom. CH each); 130.1 (arom. C);
130.6 (2 arom. CH); 131.1 (2 arom. CH); 135.4, 136.6, 147.3, 163.3 (arom. C each); 170.8, 171.6 (2 CO).
EI-MS (70 eV): 347 (20), 346 (100, Mþ), 273 (23), 272 (56), 258 (13), 257 (62), 240 (22), 213 (11), 184
(27), 51 (8). HR-EI-MS: 346.0879 (Mþ, C18H18O5Sþ; calc. 346.0870).
Methyl 2-Hydroxy-6-(2-methoxy-2-oxoethyl)-4-[(naphthalen-2-yl)sulfanyl]benzoate (3f). Starting
with 2f (495 mg, 1.5 mmol) and 1 (234 mg, 1.5 mmol), 3f was isolated as a highly viscous colorless oil
(458 mg, 80%). IR (neat): 3055w, 2995w, 2951w, 2846w, 1736s, 1659s, 1599s, 1552m, 1474m, 1436s, 1320s,
1256s, 1194s, 1163s, 1122s, 1088m, 1067m, 1022m, 998m, 952m, 895s, 843m, 745m, 705s, 688s, 562m.
1H-NMR (250 MHz, CDCl3): 3.60 (s, MeO); 3.72 (s, CH2); 3.79 (s, MeO); 6.43 (s, 1 arom. H); 6.49 (s, 1
arom. H); 7.32 – 7.45 (m, 7 arom. H); 11.26 (s, OH). 13C-NMR (63 MHz, CDCl3): 41.1 (CH2); 51.9
(MeO); 52.0 (MeO); 109.0 (arom. C); 114.8, 122.2, 129.0 (arom. CH each); 129.9, 130.0 (2 arom. CH
each); 130.1 (arom. C); 134.4 (2 arom. CH); 136.6, 138.4, 139.2, 147.3, 163.3 (arom. C each); 170.8, 171.6
(2 CO). EI-MS (70 eV): 383 (11), 382 (51, Mþ), 322 (9), 317 (16), 316 (31), 273 (23), 272 (56), 258 (13),
257 (62), 240 (22), 213 (11), 184 (27), 51 (8). HR-EI-MS: 382.0870 (Mþ, C21H18O5Sþ; calc. 382.0870).
Methyl 6-Hydroxy-2-(2-methoxy-2-oxoethyl)-3-methyl-4-(phenylsulfanyl)benzoate (3g). Starting
with 2g (441 mg, 1.5 mmol) and 1 (234 mg, 1.5 mmol), 3g was isolated as a highly viscous colorless oil
(306 mg, 59%). IR (neat): 3056w, 2996w, 2950w, 2846w, 1736s, 1659s, 1599s, 1552m, 1474m, 1436s, 1320s,
1256s, 1194s, 1163s, 1122s, 1088m, 1067m, 1022m, 998m, 952m, 895s, 843m, 745m, 705s, 689s, 562m.
1H-NMR (250 MHz, CDCl3): 2.32 (s, Me); 3.53 (s, MeO); 3.67 (s, MeO); 3.77 (s, CH2); 6.49 (s, 1 arom.
H); 7.32 – 7.63 (m, 5 arom. H); 10.77 (s, OH). 13C-NMR (63 MHz, CDCl3): 15.8 (Me); 38.2 (CH2); 51.0
(MeO); 52.2 (MeO); 109.2 (arom. C); 112.9 (arom. CH); 125.4 (arom. C); 129.9, 135.3 (2 arom. CH
each); 135.4 (arom. CH); 140.5, 145.6, 146.3, 155.8 (arom. C each); 165.5, 169.0 (2 CO). EI-MS (70 eV):
347 (20), 346 (100, Mþ), 273 (23), 272 (56), 258 (13), 257 (62), 240 (22), 213 (11), 184 (27), 51 (8). HR-
EI-MS: 346.0879 (Mþ, C18H18O5Sþ; calc. 346.0870).
Methyl 4-[(4-Fluorophenyl)sulfanyl]-6-hydroxy-2-(2-methoxy-2-oxoethyl)-3-methylbenzoate (3h).
Starting with 2h (468 mg, 1.5 mmol) and 1 (234 mg, 1.5 mmol), 3h was isolated as a highly viscous
colorless oil (273 mg, 50%). IR (neat): 3055w, 2996w, 2950w, 2846w, 1736s, 1659s, 1599s, 1552m, 1474m,
1438s, 1320s, 1256s, 1194s, 1163s, 1122s, 1088m, 1067m, 1022m, 998m, 962m, 895s, 843m, 745m, 705s, 689s,
562m. 1H-NMR (250 MHz, CDCl3): 2.32 (s, Me); 3.53 (s, MeO); 3.71 (s, MeO); 3.82 (s, CH2); 6.49 (s, 1
arom. H); 7.22 – 7.48 (m, 4 arom. H); 10.77 (s, OH). 13C-NMR (63 MHz, CDCl3): 15.9 (Me); 37.5 (CH2);
51.0 (MeO); 52.2 (MeO); 110.2 (arom. C); 111.5 (arom. CH); 125.4 (arom. C); 129.9, 135.3 (2 arom. CH
each); 140.5, 150.8, 151.5, 155.8, 159.0 (arom. C each); 165.5, 169.0 (2 CO). EI-MS (70 eV): 365 (18), 364
(100, Mþ), 333 (23), 332 (64), 305 (34), 304 (89), 273 (23), 272 (56), 258 (13), 257 (62), 240 (22), 213
(11), 184 (27), 51 (8). HR-EI-MS: 364.0770 (Mþ, C18H17FO5Sþ; calc. 364.0775).
Methyl 4-[(4-Chlorophenyl)sulfanyl]-2-hydroxy-6-(2-methoxy-2-oxoethyl)benzoate (3i). Starting
with 2i (471 mg, 1.5 mmol) and 1 (234 mg, 1.5 mmol), 3i was isolated as a highly viscous colorless oil
(357 mg, 65%). IR (neat): 3055w, 2996w, 2950w, 2846w, 1736s, 1659s, 1599s, 1552m, 1474m, 1436s, 1320s,
1256s, 1194s, 1163s, 1122s, 1088m, 1067m, 1022m, 998m, 952m, 895s, 843m, 745m, 705s, 689s, 562m.
1H-NMR (250 MHz, CDCl3): 3.47 (s, MeO); 3.59 (s, MeO); 3.69 (s, CH2); 6.43 (s, 1 arom. H); 6.49 (s, 1
arom. H); 7.11 – 7.34 (m, 4 arom. H); 11.26 (s, OH). 13C-NMR (63 MHz, CDCl3): 38.3 (CH2); 52.9
(MeO); 53.2 (MeO); 109.0 (arom. C); 114.5, 129.0 (arom. CH each); 129.9 (2 arom. CH); 130.1 (arom.
C); 134.8 (2 arom. CH); 136.6, 137.5, 147.3, 163.3 (arom. C each); 170.8, 171.6 (2 CO). EI-MS (70 eV):
368 (37), 367 (18), 366 (100, Mþ), 334 (21), 273 (23), 272 (56), 258 (13), 257 (62), 240 (22), 213 (11), 184
(27), 51 (8). HR-EI-MS: 366.0322 (Mþ, C17H15ClO5Sþ; calc. 366.0323).
Methyl 4-[(4-Ethylphenyl)sulfanyl]-2-hydroxy-6-(2-methoxy-2-oxoethyl)benzoate (3j). Starting with
2j (462 mg, 1.5 mmol) and 1 (234 mg, 1.5 mmol), 3j was isolated as a highly viscous colorless oil (432 mg,
80%). IR (neat): 3055w, 2996w, 2950w, 2846w, 1736s, 1659s, 1599s, 1552m, 1474m, 1436s, 1320s, 1256s,
1
1194s, 1163s, 1122s, 1088m, 1067m, 1022m, 998m, 952m, 895s, 843m, 745m, 705s, 689s, 562m. H-NMR
(250 MHz, CDCl3): 1.19 (t, J ¼ 7.2, MeCH2); 2.61 (q, J ¼ 7.2, MeCH2); 3.59 (s, MeO); 3.71 (s, CH2); 3.77 (s,
MeO); 6.41 (s, 1 arom. H); 6.49 (s, 1 arom. H); 7.11 – 7.38 (m, 4 arom. H); 11.28 (s, OH). 13C-NMR

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(63 MHz, CDCl3): 14.2 (Me); 27.4 (CH2); 36.5 (CH2); 50.9 (MeO); 51.2 (MeO); 109.0 (arom. C); 113.0
(arom. CH); 127.9 (2 arom. CH); 130.1 (arom. CH); 134.8 (2 arom. CH); 136.6, 137.5, 138.5, 147.3, 163.3
(arom. C each); 170.8, 171.6 (2 CO). EI-MS (70 eV): 361 (22), 360 (100, Mþ), 301 (16), 273 (23), 258
(13), 257 (62), 240 (22), 213 (11), 184 (27), 51 (8). HR-EI-MS: 360.1026 (Mþ, C19H20O5Sþ; calc.
360.1026).
Methyl 4-[(4-Ethylphenyl)sulfanyl]-6-hydroxy-2-(2-methoxy-2-oxoethyl)-3-methylbenzoate (3k).
Starting with 2k (483 mg, 1.5 mmol) and 1 (234 mg, 1.5 mmol), 3k was isolated as a highly viscous
colorless oil (404 mg, 72%). IR (neat): 3055w, 2996w, 2950w, 2846w, 1736s, 1659s, 1599s, 1552m, 1474m,
1436s, 1320s, 1256s, 1194s, 1163s, 1122s, 1088m, 1067m, 1022m, 998m, 952m, 895s, 843m, 745m, 705s, 689s,
562m. 1H-NMR (250 MHz, CDCl3): 1.19 (t, J ¼ 7.1, MeCH2); 2.23 (s, Me); 2.61 (q, J ¼ 7.1, MeCH2); 3.64
(s, MeO); 3.79 (s, MeO); 3.89 (s, CH2); 6.49 (s, 1 arom. H); 7.11 – 7.44 (m, 4 arom. H); 11.28 (s, OH).
13C-NMR (63 MHz, CDCl3): 14.2 (Me); 15.0 (Me); 27.4 (CH2); 36.5 (CH2); 50.9 (MeO); 51.2 (MeO);
109.0 (arom. C); 113.0 (arom. CH); 127.9 (2 arom. CH); 130.1 (arom. C); 134.8 (2 arom. CH); 136.6,
137.5, 138.5, 147.3, 163.3 (arom. C each); 170.8, 171.6 (2 CO). EI-MS (70 eV): 376 (22), 374 (100, Mþ),
334 (21), 273 (23), 258 (13), 257 (62), 240 (22), 213 (11), 184 (27), 51 (8). HR-EI-MS: 374.0322 (Mþ,
C20H22O5Sþ; calc. 374.0323).
Methyl 4-[(4-Chlorophenyl)sulfanyl]-6-hydroxy-2-(2-methoxy-2-oxoethyl)-3-methylbenzoate (3l).
Starting with 2l (492 mg, 1.5 mmol) and 1 (234 mg, 1.5 mmol), 3l was isolated as a highly viscous
colorless oil (313 mg, 55%). IR (neat): 3055w, 2996w, 2950w, 2846w, 1736s, 1659s, 1599s, 1552m, 1474m,
1438s, 1320s, 1256s, 1194s, 1163s, 1122s, 1088m, 1067m, 1022m, 998m, 962m, 895s, 843m, 745m, 705s, 689s,
562m. 1H-NMR (250 MHz, CDCl3): 2.34 (s, Me); 3.53 (s, MeO); 3.69 (s, MeO); 3.79 (s, CH2); 6.49 (s, 1
arom. H); 7.22 – 7.48 (m, 4 arom. H); 10.77 (s, OH). 13C-NMR (63 MHz, CDCl3): 16.2 (Me); 38.2 (CH2);
51.0 (MeO); 52.2 (MeO); 109.2 (arom. C); 112.9 (arom. CH); 125.4 (arom. C); 129.9, 135.3 (2 arom. CH
each); 140.5, 145.6, 151.5, 155.8, 159.0 (arom. C each); 165.5, 169.0 (2 CO). EI-MS (70 eV): 381 (17), 380
(100, Mþ), 350 (23), 349 (21), 348 (62), 322 (29), 321 (30), 320 (79), 273 (23), 272 (56), 258 (13), 257
(62), 240 (22), 213 (11), 184 (27), 51 (8). HR-EI-MS: 380.0476 (Mþ, C18H17ClO5Sþ; calc. 380.0480).
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.
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Received September 30, 2009